Iusmhistology - New pages [en]

P's NBME study guide

24.15.60.132 — Sun, 17 Apr 2011 23:58:55 GMT

146.9.242.88: /* Intercalated disks */

===Contraction in detail===
*If Ca+ is low, then tropomyosin will inhibit myosin to bind to thin filament.
**So ADP and Pi will be held on myosin but bind and contraction are not occurring.
*If Ca+ rises to 1 micromolar or greater, then Ca binds to TnC (troponin subunit of thin filament).
*TnI and TnT (parts of troponin) then are involved in conformational change.
**TnI binds actin.
**TnT binds tropomyosin.
*Calcium binding on troponin changes the conformation of troponin such that TnI comes up off actin which allows tropomyosin to move about 5 minutes around

the clock face of the actin.
*This allows the head of myosin to bind in on the thing filament.
*Upon binding to actin, the Pi is released from myosin. This causes a conformational change--the '''power stroke'''.
*ADP is then released placing the apparatus in a "rigor mortis" state. ATP must mind before actin is released from myosin.

===Intercalated disks===
**Fascia adherens
***Where thin filaments are joined together.
***A bit like zonula adherens.
***Where thin filaments joined to function as one between cells.
**Macula adherens
***Just a desmosome
***Where thick filaments pass between cells (?).
**Gap juctions
***Electrical connections.
***membranes come together very close at gap jucntions
***Don't physically hold cells together because they don't affect cytoskeleton.
***Occur along the longitudinal axis of the muscle cells, generally.

==NERVOUS SYSTEM ==

===Astrocytes===
*Most numerous glial cells in CNS
*Two types
**Fibrous:
***Long, thin processes
**Protoplasmic astrocytes:
***Found in grey matter
***Short and fat processes
*Have end feet: connect to epithelium and sit on the external surface of the CNS
*Provide physical support for neurons
*Maintain homeostasis (toxin processing, extra NT processing, etc)
*Release neurotrophic factors (regulate transuction, still unknown)
*Can be found between two neurons and may help transduce signals
*Astrocytes can interact with neurons through the neuron's spine and their own form of a spine.
*Astrocytes are increased after ischemia of the brain (cns).
**So in early ischemia, astrocytes may proliferate in order to rescue the neurons.
**When ischemia is severe enough that neurons don't survive, the astrocytes generate a type of scarring material.

===Blood brain barrier===
*Has four components:v Endothelial cells , basement membrane, end feet of astrocytes, pericytes

===Microglia===
*These are macrophages in the CNS

===PERIPHERAL NERVE===

====Slide 9 sciatic nerve dog====

=====Slide 17 Spinal cord ganglion, mammal=====
*The dorsal root sends afferent ("at" the CNS) fibers from the dorsal root ganglion to the dorsal horn of the spinal cord grey matter.
*The ventral root carries efferent ("exit" the CNS) fibers from the spinal cord to to visceral motor effectors.
*The ventral horn contains cell bodies of somatic motor neurons.

*The lateral horn houses cell bodies of autonomic motor neurons that innervate smooth muscle and glands.

*Somatic motor neuron axons run through the ventral root and bypass the DRG.
*Visceral motor neurons have cell bodies in the ventral horn; axons travel through the ventral root, bypass the dorsal root ganglion, follow nerves that lead

to peripheral ganglia.
**Note that this is a one-cell communication between the CNS (spinal cord) and the effector cell (skeletal muscle).
*The autonomic nervous system takes two cells for CNS-to-effector communication.
**Here there are preganglionic cells and post ganglionic cells with ganglia as their point of synapse.
**The cell body of the preganglionic cells is in the spinal cord.
**The cell body of the postganglionic cells is in the respective ganglia.
*There are two divisions to the autonomic nervous system: parasympathetic and sympathetic.
**The sympathetic system is characterized by short pre-ganglionic axons that synapse in ganglia that is very near to the spinal cord (think "sympathetic

chain ganglion", etc.).
***Subsequently, the post-ganglionic fibers are much longer as they run to their effector cells.
**The parasympathetic system is characterized by long pre-ganglionic fibers that run to ganglia that are far from the spinal cord.
***Subsequently, the post-ganglionic fibers of parasympathetics are short fibers that run to effector cells that are close to their ganglia.

==Epithelium lecture==

====Tight jxn====
*Tight jxns = zonula occludins
*There are several protein components:
**ZO1 and ZO2 (zonulin occludin)
**Claudin
**Occludin

===The belt desomosome===
*At the top of the cell, below the zonula occludin.

===Hemi-desmosome===
*These occur ont he base of the cells, to connect them to ECM (connective tissue).

===Gap jxn===
*Connexons make up these pores.

===Basement membrane===
*Has a lamina densa and one or two lamina rara (lamina lucida)
*BM formed by type 4 collagen.
**This type does not form fibrils.
*There are lots of glycoproteins in bm:
**laminin
*proteoglycans, too

==Circulatory==

===Histology of vessels===
*Layer closest to the blood is ''tunica intima''.
*Outside most layer is called ''tunica adventitia'' or ''tunica externa''.
*In between is the ''tuica intermedia''
**Contains muscle

===Capillaries===
*They only have the tunica intima.
*Sometimes have pericytes with them
*Continuous capilarries:
**Have a relatively thick (though very thin) extension of cytoplasm
*Fenestrated capilarries
**Have windows = fenetre in french
**Found in kidney, GI, and endocrine glands (pit, thryroid)
**More leaky than continuous
*Fenestrated capilarries without diaphragm
**Have windows
**Found in the renal glomerulus
**More leaky than fenestrated with
*Sinusoidal capilarries
**Bone marrow, liver, lymphod tissue
**Where lots of proteins move in and out of blood

====Image examples====
*Pinocytotic vessles are much like the fenestra.
**Also called caveoli
**Can fuse to cause little diaphrams
*Diaphragm of fenestra
**Made of PB1 and other proteins
**PB1 forms fibrilar spokes across the fenestra.

*Tunica intima:
**In healthy tissue, all vessels contain only simple squamous epithelium called endothelium.
**large elastic artery:
**medium (muscular) artery:
**arteriole:
**capillary:
**venule:
**medium vein:
**large vein: the '''exception'''
***tunica intima of the large veins is a thicker layer as it includes connective tissue and smooth muscle.

*Tunica media:
**Manifests itself as smooth muscle in all vessles (except caps and venules where it does not exist)
**Some layers consist of additional materials
**large elastic artery: has elastic ''layers'' (lamini)
**medium (muscular) artery: has elastic ''fibers'' not ''layers''
**arteriole: not much eleastic fiber
**capillary: no tunica media at all
**venule: no tunica media at all
**medium vein:
**large vein:

*Tunica adventitia:
**On the outside
**Found on all larger vessels
**More on veins (that is, larger walls) than on arteries
**large elastic artery:
**medium (muscular) artery:
**arteriole:
**capillary:
**venule:
**medium vein:
**large vein: the '''exception'''
***has connective tissue
***has longitudinal bundles of smooth muscle

==Connective Tissue==
*Imagine the oldest person you know...naked. That's connective tissue deficiency.

===Twin study===
*This is called elastosis
**Collagena ndn elastic fibers are losing their strength.

===Ground substance===
*Made up of glycosaminoglycans and ...

*Glycosamino glycans:
**Put into aggregates via hylauronic acid.

*Glycosaminoglycans (GAGs)
**There are multiple flavors.
**Syndecan (integral membrane protein)
**Versican (
**Aggrecan

====Another componetn of ground substance====
*Laminin (not lamin)
**Binding sites for just about everything in the BM
***Type IV collagen
***Heparin sulfate
***Integrins
***Collagens, sulfates, lipids, etc.

*Fibronectin
**Again, a velcro
**many binding sites

====Integrins====
*Dimeric proteins with alpha an dbeta subunit.
*Connect via talon on the inside of the membrane
*Signaling goes inward and outward.
*This is how the cell knows where it is and who its neighbors are and what it should be doing.

===Collagen===
*Gly-X-Y repeats are really impt.
**Forms a left handed helix.
**However, collagen is always found in triple helix turn that has a right handed turn.

====Fibrillar collagens====
*1, 2, and 3 for '''fibrils'''
**only visible in em
*1 and 3 also form collagen '''fibers'''
*Fibrils spontaneously line up in head to tail conformation
**In an EM, this is a big hint that you're looking at some type of collagen.

====Type 4 collagen====
*Interuptions allow for flexible kinks.
*Head molecule allows for interaction with other collagen fibers.
**Thisis the foundation of the BM.
*Perlecans help hold the mesh together.

===Collagen synthesis===
*Requires vit c; survvy
*Glycosylation in ER

===Elastic fibers===

====State 1====
*Oxytalan fibers
*Resist stretch
*When oxytalon fibers are lost, skin just hangs.

====Stage 2====
*Elaunin
*At this stage, deposits of elastin are irregularlly place thorught he scaffold of oxytalan.
*Elastin is a globular protein with glycine and proline in it.

====Stage 3====
*As secretion (by fb) continues, the elastin fibers crosslink (giving stretchability) and organizes in a regular way between fibrils.
*This gives skin the smooth and supple look.

===Loose connective tissue versus dense===
*Loose connetive:
**Fibers in all directions

*Dense irregular
**Not as many cells
**No specific orientation
*Dense regular tissue
**Tendons and ligaments
**All fibers in one direction

==Connective Cells==

====Red marrow====
*Stroma
**Where cells reside
*Hematopoietic cords
**site of blood cell formation, contains CFUs
*Sinusoidal capillaries
**Blind ends

===Erythroblasts===
*Erythropoietin (made by kidney) stimulates macrophage

====RBC membrane====
*Spectrin and anchorin are key in discoid shape.

=====Neuts=====
*60-70 % of leukocytes
*Number of sengments of nucleus is indicative of cell's age.
*Young neuts = band cells (horse-shoe shaped nuc)
*Have p-selectin ligands for slowing and tumbling on endothelium.

=====Eosinophils=====
*2-4% of the
*2-5 nuclei sections

=====Basophils=====
*< 1% of leukocytes
*Irregular nuc
**Usually bilobed
**Hard to sse because granules stain so well

*Proteins:
**Heparin, histamine
**mediate inflammation
**Act much like mast cells

====Agranulocytes====

=====Thrombocytes=====
*There is an open system (an invagination of the membrane)
**For nutrient uptake
*Tubular system
**Microfilaments that wrap around the cell
**Release things from cells

==Lymphoid organs==

===Cell type localization in lymphoid organs===

====Thymus====
*Hassall's corpuscles consist of epithelial reticular cells in concentric circles with keratin filaments filling the cells.

=====Activity of the cortex and medulla=====
*The cortex is isolated from circulation which is important so that T cells don't get away before they have been selected.
*There are three structures that generate this Thymocyte-Blood barrier:
**Continuous capillaries with tight junctions and a basal lamina; this keeps T cells from moving away aberantly.
**Reticulocytes (type I) that are bound to one another with desomsomes to help stop
**Perivascular connective tissue occupied by macrphages

*The boy in the bubble
**SCID pt, no B cell, T cell, or NK
**Mutation in the gamma chain of some receptor.

*Tonsils:
**Tonsils are considered partially encapsulated
***The capsule is only found on the side that faces the oral cavity.
***This is useful for keeping microorganisms out.
**Palatine tonsils, pharyngeal tonsils, and lingual tonsils.

====Encapsulated lymphoid organ organization====

=====Spleen=====

======Blood flow in the spleen=====
*The splenic artery branches to form '''trabecular arteries''' which give rise to '''central arteries''' which follow the trabeculae.
*The central arteries are surrounded by white pulp and the T cells within.
*After traveling past the white pulp, the arteries split again into penicular vessels.
*Penicular vessels are a specialized set of vessels that carry blood into the red pulp.
*Penicular vessels pass blood into '''sheathed capillaries'''.
**Sheathed capillaries are surrounded by macrophages, not by endothelial cells.
*At the red pulp, blood splits it's flow: closed circulation or open circulation.
*Closed circulation:
**This type of circulation is called closed because the blood is continuously bound by endothelial cells of the vessel walls.
**In closed circulation, the penicullar arterioles and capillaries connect to the sinusoids.
**In closed circulation, macrophages reach between the endothelial cells to detect and destroy old erythrocytes.
*Open circulation:
**Open circulation allows blood to flow into the stroma of the splenic cords.
**The penicular arterioles are open-ended and thus let the blood flow directly into the splenic cords.
**In the stroma, macrophages destroy aged / abnormal erythrocytes or any erythrocyitic chunks floating about.
***Aged RBCs are targeted because their membrane is not flexible enough to let them get through the basement membrane of the sinusoids thorugh which they

must pass if they want back into the circulation.
**Intact RBCs leave the stroma via trabecular veins and the splenic vein.

==RESPIRATORY SYSTEM ==
-Bowman's gland= serous glands; secretions contain odorant-binding protein (OBP) which binds odorant molecules, carries them to receptors on specialized

cilia

===Conducting region===
-Vestibule= contains vibrissae (nasal hairs);

Phacynx = connects the nasal cavity to the larynx; segments are the nasophacynx and oropharynx

Trachea= from base oflarynx. to start ofbronchial tree; hyaline cartilage rings in 'C' shaped pattern; perichondrium attached to trachealis muscle (smooth

muscle) which serves to contract lumen Bronchial Tree = from bronchi to terminal bronchioles; progressive transition to smaller diameter

Bronchioles = no glands or cartilage but still has smooth muscle; some goblet cells; progressive transition from ciliated pseudostrati:fied columnar

epithelium to ciliated simple columnar epithelium to cuboidal; final portion is called terminal bronchiole

Clara cells = secrete alveolar fluid which serves as the aqueous phase ofsurfactant

===Respiratory region===
Alveolar ducts = contains smooth muscle and both elastic and reticular fibers

===Cells ofthe alveolar system===
-Type I {squamous alveolar cells)= flat cells that line majority ofalveolar surface; provide a minimum thickness barrier for gas exchange; contain both

desmosomes and occluding junctions

-Type II (great alveolar or 'niche' cells) =cuboidal cells located in comers ofalveoli (groups of 2-3 cells); contain lamellar bodies which secrete pulmonary

surfactant (acts to lower surface tension such that less pressure is required to keep alveoli open); can differentiate to replace injured type I cells

Neonatal respiratory distress syndrome (RDS) = surfactant deficiency in premature infants (production begins at 35th week ofgestation); collapse of alveolar

walls; treated with corticosteroids which stimulates synthesis of surfactant or artificial surfactant.

-Alveolar macrophage (dust cell)= in alveolar septum and alveolar surfaces; remove degraded surfactant; either migrate up the bronchial tree or remain in the

alveolar wall for life

-Endothelial cells= Thin, no fenestrations; express angiotensin-converting enzyme (important in control ofblood volume/pressure)

Fused basement membranes

===Blood-air barrier===
Three components: 1) Surface lining and cytoplasm ofthe alveolar cells 2) Fused basement membrane ofthe alveolar and endothelial cells 3) Cytoplasm ofthe

endothelial cell

===Pleura ===
Serous membrane covering the lung that serves to facilitate sliding during respiration

==GI==

====Hard palate====
*Parakeratinized = for dealing with rough surfaces

====Tongue====
*Filiform papillae provide roughness.
*Filiform are rod like and have a parakeratinized surface.
*Fungiform papillae have bulbous ends.
**These are the red bumps on our tongues.
*Circumvallate papillae
**Valleys are flushed by serous glands called glands of Von Ebner.
*Geographic tongue
**A kind of psoriasis of the tongue.

====Gingiva====
*Gingiva = gums of the mouth.
**The epithelial attachment of gottlieb is where the gum epithelial cells attach to the mineral surface of the tooth.

*Enamel covers the crown.
**Mostly appetite

=====Periodontal ligament=====
*Run between cementum and the alveolar bone.
bundles of collagen
*This is a type I collagenous structure.
*Scurvvy: teeth fall out because ligament doesn't get regnerated becuase new collagen can't be generated.

===Gut tube===

===Esophagus===
*Statified squamous non-ker epithelium (like oral cavity)
*Lamina propria:
**Has no glands (for the most part)
**Muscularis mucosae: has longitudinal muscle, not continuous
*The submucosa '''does''' have glands
*Muscularis externus
**Have inner circular and outer longitudinal muscle layers
*Serosa
**Mostly just CT (adventitia)
**Where it penetrates the diagragm (last part), has a mesothelia covering (so a true serosa).

===Stomach===
*Txn from esoph to stomach: squamous non-kera epith to simple columnar epithelium.
*Also, we start to see tubular glands.
*Lned with surface mucus cells.
*Surface invaginates into pits where glands empty.

*The cardia has pits with some mucusy glands.

*The fundus / body have glands with a neck and base (base stains more basophilically).
**At the base, staining dark are chief cells that make pepsinogen so they have lots of protein production and packaging stuff that makes them dark.
**Parietal cells of the fundus / body make acids.
**The neck region has parietal and undiffed cells.
**Base has parietal and chief cells.

*The pylorus has deep pits and shorter mucusy glands.

*Pylorus into the small intestine:
**Pits and glands convert into villi.

==GI - Small intestine through anus==

===Stomach===
*Stem cells:
**Live in the neck of the gland
*Mucus neck cells:
**Usuaqlly in neck
**Can't be distinguished versus stem cells

*Parietal cells = oxynctic cells
**In the neck
**Make acid and intrinsic factor
**Intrinsic factor binds b12 to protect fromn degradation so it can be absorbed later.
**Without factor I you have pernicious anemia (because it is hard to fix)

====Stomach images====
*Parietal cells:
**Look like fried eggs.

*Acid secretion:
**Occurs by fusion of tubulovesicles with a secretory canaliculus.
**Bicarb moves in the opposite direction of acid.

====Chief cells====
*Produce, store, and then secrete pepsinogen (a zymogen).

*Pairetal cells live in both the neck and the base of the gland.

=====Enteroendocrine cells=====
*ADUP-type (amine precursur uptake and decarobxylation): the name for production of hormone produced by these cells.
*Scattered through epithelium

====Pylorus====
*Has deeper pits and shorter glands.
*Has lot sof mucus cell sint eh glands.
*In the pylorus, gastrin is secreted.

*Gland types:
**Cardiac, fundus, body: gastric glands
**Pylorus: deepr pits and mostly just mucus glands

===Small intestine===
*Absorptive cells are called enterocytes.
*The muscularis mucosa and lamina propria are folded within the plicae circulares.
*Note that caps in the vili are pretty leaky (fenestrated) but not leaky enough for chylomicrons to get through, hence they gro throug the lymp.

====Glands of the si====
*These are simple tubular glands
*Called crypts of lieberkuhn.

*SI:
**crypts are the locaiton of stem cells
**At the very base are paneth cells
***may be important for crohn's disease.

*LI:
**Called Brunner's glands

*Muscularis externa:
**Inner cicrular, outer longitudinal.

*Nerve plexuses:
**Myenteric plexus = auerbach's: between the two layers 9of the musculara externa (inner cirular, outer longitudinal) = intrinsic innervation
**Meissner's plexus = submucosa: runs within the submucosa = extrinsic innervation
**Both are found in the large and small intestine.

===Large intesstine===
*Mucosa:
**There are simple columnar absorptive epithelial cells
*Muscularis externa:
**Has outer longitudinal muscle with special bands called tenia coli.
**Haustra are pouches that are formed.
**This is a thickening of outer longitudinal muscle bands.
**the poutches help hold the food material as it is turned into feces.

===Cell turnover===
*3-6 days in SI
*4-8 days in LI

==Glands==

===Salivary glands===
*Demilunes
**Here serous cells are found

*Two types of ducts:
**Intercalated
**Striated

*Also there are interlobular ducts in the connective tissue.
**Also called excretory

===Salivary===
*Three major are parotid (almost all serous cells), submandibular (mixed serous and mucous) and sublingual (more mucus than serous so will often look just

mucus).

====Saliva====
*Low in Na because it helps the taste bud fxn.
*Alkaline, has bicarb to buffer acid
*Protein components:
**Proline rich protiens
***Abundant
***Antibacterial
***Help coat the tooth and keep bacteria off

====Secretion====
*Serous produce fluid, protein, and zymogens
*Mucus produces mucins
*The products mix and then pass through intercalated ducts and then striated duct.
*Striated ducts are most important for removing most Na+.

====Summary====
*Most important is to know all glands have intercalated and striated and to know which type of secretion they generate.

===Pancreas===
*Two portions: endocrine and exocrine (acinar).

====Endocrine====
*Beta = insulin
*Alpha = glucagon
*Delta = somatostatin
*F cells generate pancreatic polypeptide.

====Exocrine pancreas====
*Looks like the parotid in that it is made of acini.
**But has not fatty tissue
**Has no striated ducts

*Cholesystokinin = the hormone that moves the gallbladder

*Proteases are the main product of serous cells in the pancreas:
**Trypsin
**Elastases
**Protease E
**Kallikrine
**alpha amylases
**Lipases
**nucleases

*Secretin stimulates ductal cells to generate the volume (water and salt)

*Acinar cells:
**Well staining cyto and open nuc
**These cells have lots of rER and secretory granules.

===Liver===
*70-80% of the blood comes from the hapatic portal vein.
*The rest is oxygenated and comes from the hapatic artery.

====Hepatic blood flow====
*Blood spaces are sinusoids, a form of sinusoidal capillary
**Incompletely lined with endothelium; the endothelial cells don't bind to one another

====Formation of bile====
*Three ways to understand how hepatocytes filter blood and produce and bile:
**Liver can be lobulated:
***The liver is divided into lobules that have protal veins, hepatic arteries and ducts at one side and
**Portal lobule
***Lobule is defined as all the hepatocytes that contribute bile to a given bile duct
**Hepatic acinus
***Lobule defined by hepatocytes' blood source

===Gallbladder===
*Epithlium of gall bladder are simnple columnar epithelium
**Has brush border
*Muscularis:
*True serosis is present

==Bone and Cartilage==

===Bone cells===

====Osteoclasts====
*Rank ligand essential for diff into preosteoclast and full osteoclast.
**Made by osteoblasts

*OPG
**A decoy receptors for rank ligand

*Generates a "focal zone"

*Enzymes for resorption:
**TRAP = Tartrate-resistant alkaline phosphatase
***Can be assessed in blood to know how much activity of osteoclasts is occurring
**Cathepsin K

*Houshets lacuna
**Well in bone where resorption has occurred.

===Osteoblast===
*Come from mesenchymal cells
**Need runks2 and ostrix

*Alkaline phosphatase is key protein involved in matrix production

===Osteocyte===
*Connected to each other and to the bone surface by filopodial processes
**These live in channels called canaliculi
**Connected via gap junctions.

*There is one osteocyte per lacunae.

====Genetic profile differs from osteoblasts====
*Sclerostin is a gene unique to osteocytes and not osteoblasts.

===Bone matrix===
*Made of type 1 collagen.
**A fibrous collagen.

*C-propeptide in the blood means there is bone formation

*Non-collagenous components:
**Know osteopontin, osteonectin, and ostecalcin
**Osteocalcin is a biomarker that can be measured in the blood to know how much osteoblast activity (bone formation) there is.

===Tyeps of bone tissue===

====Woven bone====
*AKA primary bone and Immature bone
*Not very common in the adult skeleton
*Found only when there is a bone injury or in some pathological state
*This is the type of bone that is formed when you need bone right now.
**Provides rapid stabiliation
*Not very organized
*Osteoid spit out in all directions
*Relatively low mechanical strength.

====Lamellar bone====
*AKA secondary bone, mature bone
*Higher mecanical strength than primary.
*Lamellae:
**Differing patterns of collagen organization
**Result in high birefringence
***The ability to refract light differently.
**This is a product of the alternating pattern of collagen fibers.

===Bone anatomy===
*Cortical is called compact
**This is the outer part
**Main fxn is structural
**PRovide resistance to loading

*Cancellous bone = spongy bone = trabecular
**NOT squishy
**Small piece of cancellous and small piece of cortical would looke the same.

====Haversion systems====
*AKA osteons
*Perferating canals = volkman (?) canals

====Periosteum====
*This layer is tightly adherent to the bone
*Both cellular and fibrous layers

====Endosteum====
*Endosteum is similar to periosteum but is on the inside of the bone
**Endostium '''has only cells'''.

===Structures===

==Cartilage==

===Hyline cartilage===
*Made of type 2 collagen fibrils

*Proteoglycan aggregates

*Chondronectin
**Holds cells in place on the collagen and proteoglycans

*Condrocytes:
**These units are called isogenous groups.

*Hyline matrix:
**Terirtorial matrix = capsular
***Found just around a chondrocyte
**INterteritorial matrix
***Found farther out.
**The collagen fibrils are smaller in the territorial matrix

*Perichondrium
**Fibrous tissue that lines the outside of hyline cartilage in most but not all locations of hyline cartilage
**Allows connection of muscle to cartilage
**Supplies the cells that can differentiate into chondroblasts (which diff into chondrocytes)

===Fibrocartilage===
*Found mostly in IV disks
*Has type 1 collagen in it.
**Forms fibers called rows or chords
*Has no perichondrium

===Elastic cartilage===
*Found in the ear, epiglottis, and the larynx
*Has type 2 collagen
*Elastic fibers also present
*Has a pericondrium
*Looks much like hyline but you can see fibers in it.

==Joints==

===Synarthroses===
*Very little movement

===Diarthrovidal (synovial) joints===
*Have a cavity with fluid

====Articular cartilage====
*This is hyline cartilage
*Articular cartilage has type 2 collagen with '''fibrils''' not ''fibers''.

*There are several zones:
**Superficial zone: in intimate contact with the cavity; has very few condrocytes; mostly type 2 collage fibrils; resists sheer forces
**Intermediate (transitional) zone: a transition from superficial to radial
**Radial (deep) zone: large number of chondrocytes; large number of collagen fibrils; compresses to absorb forces; lysogenous groups; interterritorial

regions, etc.
**Calcified zone: interface between unminderalized cartilage of the radial and the subchondrial bone (first part of the zone); distinct from radial by way of

tidemark

====Joint capsule====
*Capsule is continuous with the periosteum
*Periostium has two layers: fibrous and cellular layer
**As it starts to cover the capsule, though, it loses it's cellular layer.

*Surface of the synovial membrane is not covered with epithelial cells
**A rare occurance in the body.

*Type A Synoviocyte:
**Found on surface of the synovial membrane
**Look like epithelium but are not because they are not connected together.
**Act like macrophages to detect and phag foreign particles.
**Uusually 1 cell deep but can be 2 to 3 deep.

*Type B Synoviocyte:
**A fibroblast like cell
**Makes hyaluronic acid
**Look much like fibroblasts

*No perichondrium on ends of bones

====Osteoarthritis and Rheumatoid arthritis====
*OA:
**Mechanical
**Rubbing of bone without cartilage
*RA:
**INflammation occurs
**osteoclasts "wreak havoc" on the cavity

==Chondrogenesis==
*When matrix made "within" existing cartilage, the cells will separate from one another; this is how the bone is lengthened at the epiphyseal plates.
*When matrix is grown around a chondrocyte the cells do not move (adding new matrix onto a surface that already exists); used in lung tissue development.

==Intramembraneous bone formation==
*In craniofacial bones, mesenchymal cells get the signal to be osteoblasts, then aggregate to form a bone blastema.
*Then they secrete matrix to form the ''primary bone tissue'' with osteoblasts around the outside and some osteobalsts in the middle.
*Bone spicules are formed through intramembraneous ossification.

==Endochondrial bone formation==
*Here we start with a template on and in which we build bone.

*There are 5 zones.
**Zone of rest: (shallowest from the articular surface to the middle of the bone): no activity by chondrocytes
**Zone of proliferation: chondrocytes become align and form rows and columns of chondrocytes (stacked coins) which contributes to bone growth as they push

the entire bone unit to increase in length
***Can see rows of fairly flat chondrocytes.
**Zone of hypertrophy: all the chondrocytes hypertrophy; causes bone lengthening
***Has larger cells than proliferative, but still has a similar staining matrix (lightness versus darkness).
**Zone of calcified cartilage: chondrocytes start to die off as they can't get nutrients
***Distinct from the zone of hypertrophy because the matrix is much darker.
**Zone of ossification: bone formation on top of the calcified cartilage template; cartilage is resorbed by osteoclasts.
***Distinct from the zone of calcification because the matrix turns light again (but a little different coloring than the proliferative).

==Fracture healing==
*Two types: primary and secondary.

*Primary
**occurs when you have a very stable fracture; no movement (perhaps because of a plate and screws put in by orthopod).
**Then bone can form without fibrous tissue or cartilage formation.
**Can get osteons to remodel through the fractured zone.
**There is no additional tissue being formed (see secondary repair)

*Secondary bone healing:
**Useful when fracture is unstalbe; whats happening when casted
**Bone '''and cartilage''' formation occur
**The more stable (the less strain) the less cartilage, the more bone.

==Bone remodeling==

===Cartoon===
*The reversal zone is where the osteoclasts are not resorbing but the osteoblasts have yet to arrive.
*This process is not limited to trabechular bone but also in cortical bone.

===Activation===
*The two major signals are death of an osteocyte or a microcrack in the bone.

===Reversal===
*First the osteoblasts must clean up
**They lay down a very thin matrix called the cement line.

*Once they reach near the normal bone surface, the last osteoblasts become lining cells.

===Bone modeling===
*This is uncoupled: osteoblastas and clasts don't work in concert.

===Bone remodeling as a cause of bone mass loss===
*Estrogen inhibits bone resorption so when estrogen goes away, bone resorption increases.

===Diagnostics===

===Pharma===
*Anti-resorptives
**Disphophonates
**Cacitonin
**Denosumab
***A monoclonal antibody taht targets RANK-L.
***Recall that RANK-L is required for dev of osteoclasts
***Acts like OPG? (what was the endogenous decoy for RANK-L)?

==Ca, VitD, and Phosphate==

===Ca===
*Without enough calcium you have rickets (in kids) and osteomalacia (in adults).
**Here the bone doesn't mineralize.
**Deformities occur
**Rickets is reversible if you treat before closure of the growth plates.

====Hypercalcemia====
*Primary:
**Elevated PTH
**When using PTH is used as pharam, it is pulsatile--fast rise, fast fall-- it stimulates osteoblasts.
**Treatment
***MOdulate the parathyroid gland

*SEcondary
**Three examples: toxic levels of VitD, immobilization, or malignancy.
**Use antiresorptive pharma.

====Hypocalcemia====
*TX:
**Increased Ca and VitD.

===VitD===
*Calbindin is required for good CA++ absorption at the gut and VitD is a txn factor modulating txn of Calbindin.
*1 alpha hydroxylase at the kidney can be deficient to lead to VitD deficiency.
*Ultimatley these cause osteomalacia and rickets.

===Phosphate===
*REgulation is athe kidney
*ABsorbed in the duodenum
**Can be CA dependent or independ
**Also regulated by vitD.

*Osteocytes secrete FGF23 and PTH from parathyroid act on kidney to reduce Na-Phosphate co-transporter
**Causes icnreased loss of phosphate.

*When phosphate is low:
**Vitd 1,25 goes up (increase resorption at the gut)
**PTH and FGF23 go down (decrease loss at the kidney)
*When phosphate high:
**vitd 1,25 is low (lower resportion at the gut)
**Increased PHT and fGF23 (increase loss at the kidney)

==Urinary 1==
http://image.wistatutor.com/content/excretion/malpighian-nephron-structure.jpeg

===Cortex and Medulla===
*Urine is produced by '''lobes''' which contain a single '''renal papillum''' which dumps urine into the '''pelvis''' which dumps into the ureter.

http://www.sweethaven02.com/MedTech/AnatPhys/human01_37.jpg

http://iws.collin.edu/mweis/Images/Dissections/pig%20dissections/pig%20dissections%20labeled/pig_kidney_cortex_medulla_calyces_labeled.png

===More on macrostructure===
*Medullary pyramids are separated by '''renal columns of Bertin'''.

http://www.sci.sdsu.edu/classes/bio100/Lectures/Lect16/Image271.gif

===Uniferous tubule function===
http://www.siumed.edu/~dking2/crr/images/RN003b.jpg

===Uriniferous tubule layout and embryonic development===
*The first form of a plasma filtering mechanism in the developing human embryo is called the '''mesonephric kidneys'''.
*Mesonephric kidneys reach their maximum size at 8 weeks and then undergo a large change ''and eventually are not kidney-like at all''.
*Parts of the mesonephric kidneys persist in men to form:
**the efferent ductules,
**the epididymis,
**the ductus deferens, and
**the ejaculatory duct.
**so, everything ''after'' the straight tubules.

*'''The metanephros gives rise to the permanent kidneys.'''
**The metanephros contains the '''metanephric mesenchyme''' and the '''uritic bud'''.
**The uritic bud and the metanephric mesenchyme are both composed of epithelial cells.
*The uritic bud grows up into the '''nephrogenic mesoderm''' which is part of the metanephros.

===Uritic bud and nephrogenic mesoderm interaction===
*The uritic bud grows into the nephrogenic mesoderm to form the mature uriniferous tubules.
*The interaction between the uritic bud and the nephrogenic mesoderm is called '''reciprocal induction'''.

*As the uritic bud grows into the nephrogenic mesenchyme, the '''uritic bud''' is the primary epithelial cell tubule structure that will become the

collecting duct.
**Recall that mesenchymal cells are connective tissue cells.
**Recall that mesenchyme looks like loose connective tissue with lots of spindly, undifferentiated cells within.
*Renal corpuscles develop along the length of the uritic bud (that is, the developing collecting duct) and therefore can originate from the tip of the uritic

bud or from epithelium that develops along side the uritic bud.

*Renal corpuscle and nephron development from the tip of the uritic bud:
**At the tops of the uritic bud, mesenchymal cells of the nephrogenic mesenchyme '''condense''' and are induced to make a '''mesenchymal-epithelial

transition''' (MET).
***Condensation includes proliferation
**These MET cells will become the epithelial cells of the glomerular capsule.
**The bud tip then expands to develop the PCT (proximal convoluted tuble), loop of Henle (LoH), and the DCT (distal convoluted tubule).
**The MET shifted cells of the early glomeruli recruit the formation of blood vessels that will become the glomerular capillaries.

*Renal corpuscle and nephron development adjacent to the uritic bud:
**Along side the uritic bud, epithelial tracts form as '''S-shaped''' or '''comma-shaped''' tubule structures.
**The tops of these se epithelial tracts will become the glomeruli and the length will become the PCT, LoH, and the DCT.

*The s-shaped buds from condensation, proliferation, and MET of mesenchymal cells will form the PCT, LoH, and DCT.

http://herkules.oulu.fi/isbn9514269918/html/graphic11.jpg

http://img.medscape.com/fullsize/migrated/editorial/journalcme/2008/12499/kerecuk.fig1.gif

http://www.sonoworld.com/images/FetusItemImages/article-images/urinary_and_adrenal/prune_belly_syndromes_files/image78.jpg

===Renal corpuscle structure===
*Note that '''podocytes are a type of epithelial cell'''.
*Capillaries are a type of endothelial cell.
*Within the capillaries as they develop within the glomerular tuft, there is '''connective tissue holding the capillaries in place'''.
**This connective tissue is called '''mesangium'''.

*The visceral bowmans capsule is made up of podocytes.
*Often there is pink material in the bowmans space; it is brush border from the proximal tubule that has washed backward during fixation.
*The distal convoluted tubule (which is, like the PCT, made up of epithelial cells) passes by the afferent arteriole along side the glomerulus.
**The DCT has specialized cells called '''macula densa cells'' on the surface that is closest to the afferent arteriole.
**Macula densa cells release signals PGE2 to cause the afferent arteriole to vasodilate and ATP to cause the afferent arteriole to constrict.
**Macula densa cells are more columnar, stain darker, and have rounder nuclei than the endothelail cells of the DCT.

*Juxtaglomerular cells (also called granular cells) are endothelial cells of the afferent arteriole that contain '''granules of renin'''.
**Granular cells (AKA juxtaglomerular cells) have a large, flattened nucleus, that is more prominent than the nucleus of lacis (extraglomerular mesangial)

cells.
**Granular cells release their renin upon PGE2 binding their EP4 receptor.
**Recall that renin will activate angiotensinogen leading to angiotensin 2 and systemic vasodilation.

*Lacis cells (also called extraglomerular mesangial cells) hold the DCT, the afferent arteriole, and the glomerulus together.
**Extraglomerular mesangial cells may also have some functioning in modifying the signals released by the macula densa cells as they travel to the granular /

endothelial cells of the afferent arteriole.
**Lacis cells (extraglomerular mesangial cells) are found between the macula densa cells and the afferent arteriole endothelial cells.
**Lacis cells have a lighter stain and less prominent nucleus as compared to granular (juxtaglomerular) cells.
**Extraglomerular mesangial cells are found between the convoluted capillaries, too, and serve to hold the loops in their structure.
***In this case, the mesangial cells are located within the basement membrane.
**Lacis cells can send processes into the lumen of the capillaries between the endothelial cells.

http://sitemaker.umich.edu/ransom.lab/files/glomerulus.jpg

http://www.nature.com/ki/journal/v74/n1/images/ki2008128f4.jpg

http://cmm.ucsd.edu/farquhar/images/Res6_Fig2_EM_Podocyte.gif

http://homepage.smc.edu/wissmann_paul/physnet/anatomynet/anatomy/podocytes2.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab23/IMAGES/VASPOLE2%20B.jpg

http://www.kidneypathology.com/Imagenes/Histologia/Histo_AYG_2.jpg

===Forming a filter at the capillary-Bowman-space junction===
*The filtrate must first get through the endothelium of the capillary, then through the basement membrane, and then through the feet of podocytes.

*The endothelium of glomerular capillaries is '''fenestrated without diaphragms''' to allow only very small proteins and smaller molecules through.

*The basal lamina restricts even the smallest proteins.
**There are three layers to the basal lamina (basement membrane) of the glomerulus.
**The three layers are probably only separate in slides as a result of processing, but they are still effective markers for pathology.
**The '''lamina rara extrna''' is farthest from the lumen of the capillary.
**The '''lamina rara interna''' is closest to the lumen of the capillary.
**The '''lamina densa''' is between the ''lamina externa'' and the ''lamina interna''.
**These layers appear as a light-dark-light pattern in EM.

*Podocytes are a type of epithelial cell that provide the finest level of filtration ('''slit pore diaphragms''') of the plasma as it crosses into the Bowman

space.

*Water and small molecules pass freely into the Bowman space.
*It is still disputed what factors play the primary role in keeping proteins from entering the filtrate.
**Some say the anionic charge of the basement membrane, which would repel proteins which are generally negatively charged, is the primary factor that hinders

protein passage.
**Others point to the podocyte processes and the important proteins that make up the processes (ZO1, nephrin, Neph1) as the primary protein-hindering

mechanism.
**Nephrin seems to form a lattice between podocyte processes that would prevent proteins from passing into the bowman space.
http://www.nature.com/ki/journal/v73/n6/images/5002798f1.jpg
**Recall that '''ZO1 is associated with tight junctions'''.

===Mesangial cells===
*Recall that mesangial cells reside between capillaries within the basement membrane.
**Recall that '''basement membranes are always made of type 4 collagen!'''
*Mesangial cells may modulate capillary blood flow.
*Mesangial cells may also act as phagocytes within the basement membrane of the glomerulus.
*Mesangial cells '''reaches out and cups''' each capillary around it.
*Mesangial matrix is made up of collagen, glycans, proteoglycans, etc.

http://www.siumed.edu/~dking2/crr/images/corp5.jpg

http://herkules.oulu.fi/isbn9514264290/html/graphic55.png

http://content.answcdn.com/main/content/img/oxford/Oxford_Body/019852403x.cell.1.jpg

http://www.ndt-educational.org/images/MGP0001.jpg

===The proximal tubule===
*The proximal tubule is characterized by being large, being eosinophilic (cuboidal, continuous, uniform), and having central nuclei.
*The proximal tubule demonstrates '''cells with brush border and basolateral membrane folding in order to increase its surface area'''.
**Note that during fixation, the brush border often sloughs off into the lumen.
**The proximal straight tubule '''continues through the outer stripe''' of the outer medulla.
**"Straight segments ... terminate at a remarkably uniform level ... that establishes the boundary between the inner and outer stripes of the outer ...

medulla." per [http://en.wikipedia.org/wiki/Proximal_convoluted_tubule wikipedia]
**Note that this is true for both cortical- and juxtamedullar glomeruli-derived proximal straight tubules.

===Cell distinction along the PCT, LoH, and DCT===
*Recall that the cells of the PCT, LoH, and DCT are all epithelial cells specialized for reabsorption and / or secretion.
*There are four regions that can be distinguished by cell morphology and characteristic: PCT / thick descending limb, thin descending / thin ascending, thick

ascending / DCT, and the collecting duct.
*Note that the thick descending tubule is the same as the proximal straight tubule; the same goes for the distal region: distal straight tubule = thick

ascending tubule.

====Cells of the PCT and PST====
*Note that the '''PST = proximal straight tubule = thick descending / proximal loop'''.
*There are only epithelial cells in the PCT and thick descending loop.
*Epithelium of the PCT is a simple squamous epithelium.
*'''the cells of the PCT and thick descending tubule are the only cells with a brush border'''.
*Cells of the PCT and thick descending tubule also have nuclei that are spaced far apart.
*PCT / thick descending tubule epithelial cells stain very pink.

====Cells of the thin descending and thin ascending tubules====
*There are only epithelial cells in the thin descending and ascending tubules.
*Recall that '''the descending loop is passively, highly permeable to water and solutes.'''
*Recall that '''the ascending loop is impermeable to water and actively secretes Na and Cl.'''
*The epithelial cells of the thin regions are thin cells that stain lightly.
*The nucleus of epithelial cells of the thin tubules is smaller than other nuclei of tubular epithelial cells.

====Cells of the DST and DCT tubules====
*The epithelium of the DCT and thick ascending tubule is '''thicker than the PCT and thick descending tubule'''.
*cell types in the thick ascending and DCT tubules: epithelial cells, macula densa cells, and ''principal cells'', intercalated cells.
*Epithelial cells of the thick ascending tubule and DCT need lots of protein to facilitate ion transport and so it makes sense that '''thick ascending

epithelium and DCT epithelium have lots of mitochondria'''.
*Epithelial cells of the thick ascending tubule and DCT have '''apical nuclei that bulge outward''' (perhaps because of the mt that are pushing them

apically).
**'''Macula densa cells appear at the last part of the thick ascending tubule'''.
*The DCT is the first site of '''intercalated cells'''.

=====Differentiating PST and DST=====
*Thick descending epithelium stain darker than thick ascending epithelium.
*Thick descending epithelium has more basally located nuclei while ascending epithelium have apically located nulcei.
*Thick descending has a thicker wall than the thick ascending.

=====PCT versus PST and DCT versus DST identification=====
*Note that PST and PCT can be differentiated because they are never found in the same location: PCT is in the convoluted area and PST is only in the

medullary ray area.
*Because the DCT and DST are both bound in the cortex, it is likely impossible to tell them apart (unless the structure in question runs right up next to a

glomeruli and has macula densa at which point we know it is a DST).

http://www.ouhsc.edu/histology/Glass%20slides/35_10.jpg

http://www.medicalhistology.us/twiki/pub/Main/ChapterSeventeenSlides/b68_proximal_convoluted_tubule_kidney_40x_pas_labeled.jpg

=====Differentiationg PCT and DCT=====
*PCT and DCT can be distinguished by their stain and size:
*PCT epithelium has a brush border but DCT epithelium does not, though often the brush border is not preserved.
*PCT stains darker than DCT, though sometimes it can be the opposite, so good luck with that.
*PCT is made of larger cells than DCT (so with PCT you travel farther around the tubule before finding the next nucleus).

http://www.lab.anhb.uwa.edu.au/mb140/corepages/urinary/images/kidneydiagram.jpg

====Cells of the collecting duct====
*Epithelial cells of the collecting duct bulge into the lumen.
*Epithelial cells of the collecting duct have clear distinctions between each cell and have nuclei that ''do not bulge'' (like PCT / thick ascending tubule

epithelial cells).
*Nuclei are more basal and irregularly shaped.
*Principal cells are hormonally controlled for water reabsorption and are the '''major site of potassium regulation'''.
**Principal cells absorb Na and secrete K.
**Principal cells are generally impermeable to water but can become water absorptive when ADH is present (think AQ2).
*Intercalated cells '''stain darkly''', bulge a little into the lumen, have no brush border, have a more apical nucleus than principal cells, and are the

site of pH regulation.

*There are '''three sections to the collecting duct''': the connecting tubule and cortical collecting tubule, the outer medullary collecting tubule, and the

inner collecting tubule.
**The two proximal sections (connecting duct / cortical collecting duct and the outer medullary collecting duct) have principal '''and''' interstitial cells;

the inner medullary collecting duct has '''only principal cells'''.
**The inner medullary collecting duct is also called the '''papillary collecting duct'''.
**The last section of the inner medullary collecting duct is called the '''duct of Bellini'''.

===Distinguishing regions of the kidney===
*Note that thin segments of the LoH and DCT / PCT never occur in the same area so they can be used to determine the origin of a section.
**'''Thin loops of Henle are only found in the medulla.'''
***Recall that the thick proximal tubule terminates at the outer-inner stripe border of the medulla.
**'''Convoluted tubules are only found in the medulla.'''
*Distinguishing the medulla:
**The inner medulla has only asc / desc thin tubules and the collecting duct.
**The inner stripe of the outer medulla has asc / desc thin tubules, proximal / distal thick tubules, and the collecting duct.
**The outer stripe of the outer medulla has only thick tubules and collecting duct.
*'''There are no glomeruli in the medulla!'''

==Urinary 2==

===Loop of Henle===
*When the NaCl level is high, we want slow the filtrate flow rate so we have time to reabsorb all that valuable NaCl; therefore, when the NaCl level in the

filtrate is high macula densa cells release ATP to constrict the afferent arteriole and decrease GFR.
*Conversely, very little NaCl in the filtrate at the macula densa means that the filtrate has had lots of time to have its NaCl reabsorbed so we can speed up

GFR. In this case, macula densa cells release prostaglandins that cause renin release (and subsequently vasodilation) at the afferent arteriole.

===More kidney superstructure===
http://www.comprehensive-kidney-facts.com/images/KidneyAnatomy.jpg

*Note that '''the ascending thick tubule is deeper than the descending thick tubule'''.
*'''Arcuate vessels''' follow the boundary of the cortex and medulla, giving off '''interlobular vessels''' that give off '''afferent arterioles''' and

receive '''stellate vessels'''.

*The thick descending tubule = proximal straight tubule = pars recta.

*We can remove kidney stones through a surgery that pierces the cortex, enters a calyx, and uses a probe to grab / destroy the stone. '''Percutaneous

nephroscopy'''.

===Renal vasculature===
*The order of renal blood flow: renal artery -> inter''lobar'' artery -> arcuate artery -> cortical radial artery (imagine these radiating outward from the

arc; used to be called interlo''bu''lar arteries) -> afferent arteriole -> glomerular capillaries -> efferent arteriole.
*The return route can start from two locations:
**Superficial and mid-cortical glomerulus: (from efferent arteriole) peritubular capillaries
***superficial peritubular capillaries return via stellate veins -> arcuate vein...
***deeper peritubular capillaries return via cortical radial vein -> arcuate vein...
**Juxtamedullary glomerulus: (from efferent arteriole) descending vasa recta -> ascending vasa recta -> arcuate vein...
*Then both follow the same path away from their respective nephron: arcuate vein -> inter''lobar'' vein -> renal vein.

http://biomed.brown.edu/Courses/BI108/BI108_2001_Groups/WAK/renalphys/images/image3.jpg

===Cortex organization===
*A '''renal lobule''' is a unit of renal tissue with medullary ray at the center with cortical radial vessels bounding it on the outsides.
**So '''medullary rays are the ascending and descending tubules that will run perpendicular to the capsule of the kidney.'''
**So, '''a cortical labyrinth is a collection of renal corpuscles with their associated medullary rays'''.

===Juxtuloglomerular apparatus and the renin-angiotensin pathway===
*Renin is released by granular cells (juxtaglomerrular cells).
**Angiotensin 2 causes systemic vasodilation.
*The apparatus contains the afferent and efferent arterioles, the macula densa, and the extraglomerular cells (lacis cells).
**There are also juxtaglomerular cells which are '''smooth muscle / endocrine cells.'''

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/F16-5.jpg

http://allaboutim.webs.com/JGA%20-%203D.jpg

http://www.medicalhistology.us/twiki/pub/Main/ChapterSeventeenSlides/b67_macula_densa_renal_corpuscle_40x_he_labeled.jpg

===Post-kidney urinary ultrastructure===
*The calyces, pelvis, ureters, bladder, and uretra all have the same histological structure.
**The only exception is that the walls of the ureters become thicker as they continue.
*The calyces through bladder are '''transitional epithelium''' with a '''lamina propria''' and '''smooth muscle'''.
**Transitional epithelium allows these structures to change volume easily, which is most obviously important in the bladder.
**The lamina propria holds the cells together with connective tissue when changing volume.
**The smooth muscle allows contraction for movement of urine along the tract.

===Transitional epithelium of the bladder===
*Uroplakins can fold up like a pleat.
*A protein called '''uroplakin''' can be moved to the surface or removed from the surface via vesicular movement in order to increase or decrease surface

area.
**Vesicles that contain uroplakin are called '''fusiform cytoplasmic vescicles'''.
*Uroplakin, as with all membrane proteins, is generated via the rER and golgi apparatus.
*Where uroplakin is on the surface, the membrane is thicker; there are thinner areas of membrane that are distict in EM of bladder epithelium.

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/bladder4.jpg

http://www.orienttumor.com/zh_asp_new/zt/ENGLISH/t&t/Bladder_Cancer/001_s.jpg

http://neuromedia.neurobio.ucla.edu/campbell/urinary/wp_images/49_transitional_epithelium.gif

===Smooth muscle of the bladder===
*Smooth muscle of the calyces, pelvis, and ureters are '''helical''' in pattern.
*Smooth muscle in the bladder is '''longitudinal''' and runs in all directions.

==Endocrine histology==

===Describe the structural organization of the endocrine system===
*Note that exocrine glands secrete onto an epithelial surface that is usually in the form of a duct whereas endocrine glands secrete into the blood stream.
**Furthermore, both exocrine glands and endocrine glands are usually on the '''outside of the basement membrane''' relative to the blood.
**Therefore, exocrine glands do not secrete across the basement membrane.
**However, '''endocrine glands often must secrete their hormones across the basement membrane'''.

===Define components of the endocrine system===

===Describe the embryonic origin, histological organization, and hormone secretion of the endocrine system===

====Origin, organization, and secretion of the hypothalamus====
*The hypothalamus releases 5 hormones from three nuclei (dorsal medial, ventral medial, and infundibular nuclei):
**TRH which stimulates thyrotropes and mammotropes (lactotropes) of the anterior pituitary to release TSH and PRL.
**PIF (prolactin inhibitory factor, dopamine) which inhibits lactotropes ('''mammotropic cells''') of the anterior pituitary from releasing PRL.
**SST (somatostatin) which '''inhibits''' somatotropes and thyrotopes of the anterior pituitary (adenohypophysis) to release GH and TSH.

*The hypothalamus also contains two more nuclei that produce two other hormones that are delivered directly to the posterior pituitary (neurohypophysis)

through the axons of the neuron cells that produce the hormones.
**The '''supraoptic neucleus''' produces vasopressin (ADH, AVP) which acts on the collecting ducts of the kidney (think AQ2).
**The '''paraventricular nucleus''' produces oxytocin which acts on the mammary glands (myoepithelial cells) and uterus (smooth muscle cells, contractions).

====Origin, organization, and secretion of the pituitary gland (hypophysis)====
*The anterior pituitary consists of the pars distalis, the pars intermedia, and the pars tuberalis.
*The posterior pituitary (neurohypophysis) is made up of the pars nervosa and the median eminence.

http://academic.kellogg.edu/herbrandsonc/bio201_mckinley/f20-4_pituitary_gland_c.jpg

http://www.ouhsc.edu/histology/Glass%20slides/38_11.jpg

*The neuroectoderm (floor of the diencephalon) grows caudally, forms a stalk, and remains attached to the brain tissue of origin.
http://www.cytochemistry.net/endocrine_system/pitdraw2.jpg

=====Adenohypophysis (anterior pituitary)=====
*The pars distalis (anterior lobe):
**The pars distalis is composed of '''fibroblast generated reticular fibers''' that support hormone-generating epithelial cells and a rich bed of

'''fenestrated capillaries'''.
**Cells of the pars distalis can be classified by the way the stain: basophilic, acidophilic, and chromophobes.
**Acidophilic cells: somatotropes and mammotropes (lactotropes).
**Basophilic cells: gonadotropes, croticotropes, and thyrotropes
**Chromophobic cells: stem cells, degranulated cells that would otherwise be chromophilic (see acidophilic and basophilic).
**'''Differentiating cell types is not possible with light microscope''', only by trasmission electron microscopy can these hormone producing cells be

differentiated.
http://embryology.med.unsw.edu.au/histology/endocrine/hya40he.jpg

*The pars tuberalis:
**Most cells of the pars tuberalis are '''basophilic'''.

*The pars intermeida:
**Colloid-filled cysts fill the pars intermedia.

=====Neurohypophysis (posterior pituitary)=====
*The neurohypophysis contains '''nerve cells and glial cells (pituicytes)'''.

*The pars nervosa:
**The pars nervosa contains fibroblasts, pituicytes, mast cells and neurons.
**The neurons arise from the paraventricular and supraoptic neuclei where oxytocin and vasopressin are made, respectively.
**These neurons are atypical in that they do not synapse at their distal axons.
**The '''hormones released by these neurons are stored in granules (called Herring bodies or neurosecretory bodies''') at the distal aspect of the axon.
***Herring bodies can be identified under light microscopy.

*The infundibular stalk
**The infundibular stalk, like the pars nervosa, contains atypical nerve axon endings that release hormones.
**The neurons of the infundibular stalk release their hormones into the hypothalamus-pituitary portal system and affect the cells of the anterior pituitary.

=====Pituitary portal system=====
*There are really 4 main components to the portal system: primary and secondary capillary beds, long veins and short veins.
*The primary capillary bed arises from the superior hypophyseal artery and resides around the median eminance.
*The long veins connect the primary capillary bed to the secondary capillary bed.
*The secondary capillary bed resides around the adenohypophysis.
*The inferior hypophyseal artery forms a capillary mesh at the neurohypophysis.
*The short veins connect the capillaries of the neurohypophysis to the secondary capillary bed of the adenohypophysis.

====Origin, organization, and secretion of the Adrenal glands====
*The outer shell is made of dense connective tissue that sends '''septa into the center of the organ as trabechulae'''.
**Cortex from mesoderm, medulla from neuro ectoderm.

http://www.histology-world.com/photomicrographs/adrenallabel.jpg

=====Adrenal cortex=====
*GomiFacoRea: glomerulus-mineralocorticoids, fasciculata-corticoids, reticularis-androgens.

http://ouhsc.edu/histology/Glass%20slides/39_11.jpg
http://ouhsc.edu/histology/Glass%20slides/39_03.jpg

*The glomerulosa:
**The glomerulosa layer is characterized by '''closely-packed, arched chords of columnar or pyramidal cells''' surrounded by '''capillaries'''.
**The glomerulus can be differentiated from the capsule because of increased cellularity, prominent, circular nuclei, prominent arches, less connective

tissue (which usually stains bright pink).

*The fasciculata:
**The fasciculata is characterized by '''long chords of polyhedral cellls''' and '''fenestrated capillaries'''.
**The fasciculata can be differentiated from the glomerulosa by distinct change in from short, bulbous cellular collections to long chord-like cellular

collections.

*The reticularis:
**The reticularis can be differentiated from the fasciculata by less organized cellular collections, more eosinophilic staining (pinker, think about the

granules of norepi and epi),

http://www.vet.uga.edu/vpp/clerk/groover/Fig1.jpg

http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_%26_Physiology/A%26P202/Endocrine_System/histology_jpgs/adrenal_40x_P2252261lbd.JPG

http://wikis.lib.ncsu.edu/images/7/7a/Adrenalcortex.JPG

http://www.udel.edu/biology/Wags/histopage/colorpage/cen/cenzgf.GIF

http://withfriendship.com/images/i/43179/adrenal-medulla-hormones.jpg

=====Adrenal medulla=====
*The medulla of the adrenal is composed of '''chromaffin cells''' which can be considered like post-ganglionic neurons.
*Chromaffin cells can either be '''norepinephrine producing or epinephrine producing''' and will have '''granules full of their labors'''.
**Norepinephrine-producing Chromaffin cells are found near medullary arteries.
**Epinephrine-producing Chromaffin are found near cortical sinuses.
*Cell density within the medulla is less than that of the cortex.

http://wikis.lib.ncsu.edu/images/5/50/Adrenalmedu.jpg

http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/adrenal_gland_medulla_40x.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab24/IMAGES/ADMEDULL.jpg

http://histology-world.com/photoalbum/albums/uploads/normal_medulla40X_lbl.jpg

====Origin, organization, and secretion of the Pancreas====
*The endocrine portion of the pancreas arises '''from endodermal tissue near the bile duct'''.
**The notes also say that the endocrine protion arises '''from epithelium of the gut'''.
*There are four cell types in the endocrine islets of langerhans: beta, alpha, delta, and F / pp cells (by abundance).
*Delta cells make somatostatin.

http://www.daviddarling.info/images/islets_of_Langerhans.gif

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/islets.jpg

http://www.medicalhistology.us/twiki/pub/Main/ChapterThirteenSlides/b36_interlobular_duct_pancreas_10x_labeled.jpg

http://www.ric.edu/faculty/ptiskus/Stem_Cells/Image3.gif

====Origin, organization, and secretion of the Thyroid====
*'''Within or between''' the follicles can be found '''C cells (parafollicular cells)''' which produce '''calcitonin'''.

*Production, storage, and release of thyroid hormones '''involves both endocrine and exocrine functions'''.
*Thyroglobulin made in rER, glycocylated in rER / golgi, and moved into the lumen.

http://img.tfd.com/vet/thumbs/gr387.jpg

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/thyroid4F.jpg

http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_&_Physiology/A&P202/Endocrine_System/histology_jpgs/thyroid_400x_P2252255lbd.JPG

http://ouhsc.edu/histology/Glass%20slides/42_04.jpg

http://www.drharper.ca/images/HPT%20Axis.gif

====Origin, organization, and secretion of the Parathyroid glands====
*The Parathyroid gland '''arises from the pharyngeal pouches'''.
*Like the adrenal glands, the parathyroid glands have a '''capsule with septa that run inward'''.
*The parathyroid gland is composed of two cell populations: chief cells and oxyphil cells.

*Chief cells:
**Chief cells '''contain eosinophilic granules of PTH'''.
**Note that regulation of chief cell PTH release is an '''inhibition of inhibitoin mechanism: when serum Ca levels decrease, fewer Ca-receptors bind Ca (the

ligand) causing a decrease in intracellular signaling and an increase of PTH release'''.

*Oxyphil cells:
**The function of oxyphil cells is unknown; however, it is known that they arise during puberty.
**Oxyphil cells are '''larger than chief cells''' with an acidophilic cytoplasm and '''abnormally shaped mt'''.
**Oxyphil cells are often found in clusters at the center of the parathyroid gland or near the perimeter.
http://www.ouhsc.edu/histology/Glass%20slides/40_06.jpg

http://www.bu.edu/histology/i/15002loa.jpg

http://neuromedia.neurobio.ucla.edu/campbell/endocrines/wp_images%5C137_cells.gif

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/Image514.gif

=====Primary hyperparathyroidism=====
*Primary hyperparathyroidism is a defect with the parathyroid itself causing an '''an elevation of PTH'''.
*Giving PTH intermittently to post-menopausal women is associated with decreased risk of bone fracture.
**'''continuous administration of PTH causes bone loss yet intermittent PTH administration causes increases in bone mass'''.

====Origin, organization, and secretion of the Pineal gland====
*The pineal gland arises from '''neuroectoderm from the floor of the diencephalon''' (just like the neurohypophysis).
*The pineal gland is pine-cone shaped and covered with connective tissue.
**This pine-cone shaped pineal gland is located in the '''posterior aspect of the third ventricle'''.
http://www.rickrichards.com/chakras/pituitary_brain2a.jpg
*The pineal gland contains pinealocytes, interstitial glial cells (like astrocytes).
*The pinealocytes produce '''melatonin''' and thus take part in daily rhythmicity.
*'''Rene Descarts''' explained human behavior and thought via the pineal gland because of its involvement in sensation, imagination, memory, and bodily

movement.

http://ouhsc.edu/histology/Glass%20slides/41_02.jpg

http://embryology.med.unsw.edu.au/histology/endocrine/pin42he.jpg

====Origin, organization, and secretion of the Diffuse Neuro-endocrine system====
*Organs that have diffuse endocrine tissue include the '''heart, kidney, thymus, gut, and gonads'''.

=====Bone as an endcrine organ=====
*Two major signals are released by bone to affect physiology: FGF23 and uOCN.

*FGF23 is released by the bone and causes:
**Kidneys decrease phosphate (Pi) reabsorption resulting in decreased serium Pi.
**Kidneys decrease 1,25VitD activation resulting in decreased serum 1,25OH VitD and decreased Ca reabsorption.
**So FGF23 is generally an anti-bone-building signal.

*uOCN is released by the bone and causes:
**Pancreatic beta cells to increase insulin release resulting in decreased serum glucose.
**Adipocytes to increase adiponectin resulting in changes to glucose and fatty acid catabolism.
**Muscle to increase sensitivity to and uptake of glucose resulting in decreased serum glucose.
**So uOCN is generally a pro-growth-use-up-the-glucose signal.

*Bone also releases '''osteocalcin''' which has been shown to be associated with poor fertility when deficient.

==Female reproductive histology==

===Ovarian cycle===

====Origin and fate of ovarian follicles====
*Ovarian follicles are composed of a germ cell (oocyte) surrounded by supporting cells (follicular epithelial cells).
*Primordial germ cells originate from the yolk-sac (endoderm) and migrate to the genital ridge where the ovaries are developing.

====Ovarian anatomy====
*The cortex epithelium of the ovary is simple cuboidal epithelium.

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/A%20ovary.jpg

http://www.ouhsc.edu/histology/Glass%20slides/83_02.jpg

====Ovarian follicle====
*During the ovarian follicular phase '''mesenchymal cells will differentiate into theca cells''' to surround the follicle with an extra two layers.
**The endocrine layer of theca cells is called the '''theca interna'''; the vascular layer of theca cells is called the '''theca externa'''.
*The ovarian follicle has a specific anatomy of layers:
***Within the follicular cell population one may find a '''Call-Exner body''' which are collections of granulosa cell membrane with granulosa secretions

within.
**The follicular cells are surrounded by a '''basement membrane (basal lamina)'''.
**The basal lamina is surrounded by theca cells (from mesenchyme) which form two layers: theca interna and theca externa.

http://www.ft-patho.net/index.php?plugin=ref&page=Follicle&src=callexner.jpg

http://www.deltagen.com/target/histologyatlas/atlas_files/female_rep/ovary_10x.jpg

http://www.deltagen.com/target/histologyatlas/atlas_files/female_rep/ovary_40x.jpg

http://biology.nicerweb.com/Locked/media/med/Test/mitosis/cat_ovary.jpg

====Stages of the ovarian follicle====
http://farm4.static.flickr.com/3642/3475790550_9bf0d2c33f.jpg

http://i27.photobucket.com/albums/c190/lovesthesunset/anatomy%20and%20physiology/ovaryfollicles.jpg

*Developing follicle:
*In the developing follicle, '''the follicular cells are cuboidal''' and have proliferated and differentiated into '''granulosa cells'''.

*Secondary follicle:
*The secondary (vesicular, antral) follicle is '''uniquely defined by a developing antrum and a theca externa'''.
*Granulosa cells '''secrete stroma-weakening factors''' to allow expansion of the follicle.
**A primary stroma-weakening factor is '''plasminogen-activator''' which converts plasminogen to '''plasmin (fibrinolysin, a trypsin-like enzyme)''' which

cuts up fibrin.
*Granulosa cells '''secrete a meiosis-regulationg factors''' to inhibit movement from prophase 1 to metaphase 2 in the oocyte.
*It is in the secondary follicle stage (antral stage, vesicular stage) that the '''oocyte reaches its mature size.'''

http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/secondary.jpg

*Mature follicle:
**The corona radiata is sometimes called the '''rim'''.
**The cumulus oophorus is sometimes called the '''stalk'''.
*Mature follicles are very large: can be over 1 cm!
*As a mature follicle, the oocyte '''progresses from prophase of meiosis 1 to metaphase of meiosis 2''' and thus generates the '''first polar body'''.
**Note that having entered meiosis 2, the oocyte is called a '''secondary oocyte'''.

http://www.spcollege.edu/clw/math_science/nicotera/pnic/nicotera/ovary%201.jpg

http://t0.gstatic.com/images?q=tbn:ANd9GcR_5ajvKIDofXIvPSq_8CEqUgDbjlsBRtYNqKEDaGYemdfQoqPAtQ

http://www2.sunysuffolk.edu/sabatil/ovary400xl.gif

*Deciding on which type of follicle you're observing:
**flattened follicular cells: primordial
**cuboidal folliclar cells (with a layer on either side--zona pellucida or basal lamina): developing
**antrum / fluid: secondary follicle
**no way to distinguish secondary from mature.

http://ocw.tufts.edu/data/4/221179/221181_xlarge.jpg

http://classroom.sdmesa.edu/anatomy/Histologyphotos/Reproductive/Ovary%202.jpg

*Here is a good image (though it does not show a mature follicle):

http://academic.kellogg.edu/herbrandsonc/bio201_mckinley/f28-4a-d_ovary_c.jpg

http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_&_Physiology/A&P203/Reproductive_Tract_Histology/developing_follicle_400x_lbld_P5230104.jpg

http://www.histol.chuvashia.com/images/female/ovary-04-l.jpg

====Endocrine regulation of follicle maturation====
*'''Increased estrogen inhibits FSH release at the pituitary''' thus stopping the growth of the follicle and allowing ovulation.
*'''Increased estrogen stimulates LH release at the pituitary''' thus commencing ovulation.

*Recall these classic images:
http://faculty.stcc.edu/AandP/AP/imagesAP2/reprod/menstcyc.jpg

http://4.bp.blogspot.com/_15-2o9FAeCE/SBiYrNuBFEI/AAAAAAAAASc/9l1Usb-KOrI/s400/300px-MenstrualCycle.png

http://2.bp.blogspot.com/_UDpNzFLK85g/Sepl1zlqm0I/AAAAAAAAAJE/QEiQJB3zmxk/s400/menstrual+cycle.gif

====Ovulation====
*As the granulosa cells of the secondary and mature follicle produce more and more estrogen, more and more LH is released from the anterior pituitary gland

(adenohypophysis, pars distalis).
*Ovulation events include:
**Breakdown of the cumulus oophorus, thus the oocyte floats freely in the antrum and follicular fluid.
**Weakening of the ovarian stroma:
***Proteolytic enzymes like '''collagenase''' disrupt the stromal connective tissue.
***Granulosa cell connections weaken
***Local ischemia causes a pale spot on the surface of the ovary called a '''stigma'''.
***Follicular wall ruptures releaseing an oocyte with the corona radiata and zona pellucida surrounding.

====The corpus luteum====
*LH causes granulosa cells to become '''granulosa lutein cells''' and theca cells to become '''theca leutein''' cells.
**Granulosa lutein cells develop the morphology of a secretory cell and '''actively produce progesterone'''.
**Note that '''the production of progesterone by the granulosa lutein cells is necessary for implantation''' of the embryo.
*LH causes theca cells to become '''theca lutein cells'''.

*If pregnancy does not occur, the corpus luteum is called the '''corpus luteum of menstruation'''.
**Therefore, '''progesterone from the corpus luteum is self limiting'''.
**That is, the corpus luteum will bring about self-demise via progesterioen inhibition of pituitary-LH unless chorionic gonadotropin is generated by the

placenta.

*If pregnancy occurs, the corpus luteum is called the '''corpus luteum of pregnancy'''.
*Recall that trophoblasts of the placenta produce chorionic gonadotropin which maintains the corpus luteum (even though LH drops because of high progesterone

levels).
**hCG is the hormone used to test for pregnancy.
*Granulosa cells of the corpus luteum of pregnancy produce '''relaxin''' which has a smooth-muscle relaxing effect (histo says "during parturition",

wikipedia says "during gestation").
**'''Relaxin opposes the pro-parturition actions of oxytocin'''; that is, it keeps the smooth muscle of the uterus relaxed.
**Relaxin '''targets the fibrocartilage of the pubic symphysis''' to increase articulation.
**Note that physio notes say that the role of relaxin in pregnancy is unclear.

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/corpus%20leutum.jpg

====Follicular atresia====
*Follicular atresia generates a long-lasting, scar-tissue structure called the '''corpus albicans'''.
*The zona pellucida remains (bright pink) and a wavy line (the basement membrane, called the '''glassy membrane''').

http://zoomify.lumc.edu/histonew/female/female/dms174/27.gif

===The uterine tubes===
*The uterine tubes are muscular tubes that extend from the ovary on the posterolateral wall of the abdomen to the medioventral aspect of the abdomen and the

lateral aspect of the uterus.
*As the oviducts progresses distally, there are fewer involdings.

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab29/IMAGES/FEML26.JPG

http://www.1cro.com/Diversity/extovary.jpg

http://1.bp.blogspot.com/_YRaDDRB_iZc/TJtKfdjuPjI/AAAAAAAAKPA/lm57mEwumss/s1600/Oviduct-hen.jpg

http://www.jci.org/articles/view/29424/files/JCI0629424.f1/medium

====Layers of the oviduct====
*Like other epithelial tracts there are four major layers to the oviduct (from inner to outer): mucosa, lamina propria, muscularis, and serosa.
*'''Secretions from the oviduct promote sperm activation'''.
Does this refer to capacitation?

http://www.kumc.edu/instruction/medicine/anatomy/histoweb/female/small/Fem10s.JPG

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2020/2020%20Exam%20Reviews/Exam%205/oviduct07-vessels.bmp

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2020/2020%20Exam%20Reviews/Exam%205/oviduct05.bmp

*Mucosa of the oviduct:
*The mucosa of the oviduct is comprised of '''columnar, ciliated''' epithelial cells.
**These columnar cells are '''secretory''' and are called '''Peg cells'''.
*Estrogen (from the corpus luteum) increases the height of the columnar cells.
*Progesterone (from the corpus luteum) increases the ciliary action of the columnar epithelial cells of the mucosa.

http://faculty.sdmiramar.edu/KPETTI/Bio160/TissueHistology/SimCol-Oviduct.jpg

http://faculty.une.edu/com/abell/histo/oviduct.jpg

http://www.ansci.wisc.edu/jjp1/ansci_repro/lec/lec1/female_images/images_nolabel/oviduct%20epithelium.jpg

http://faculty.une.edu/com/abell/histo/ampovidw.jpg

*Lamina propria:
*The lamina propria of the oviduct is '''highly vascularized'''.

http://faculty.une.edu/com/abell/histo/oviduct2w.jpg

*Muscularis:
*As with so many muscularis layers, there is an '''inner circular''' and '''outer longitudinal''' layer.
*The two layers of the muscularis are '''interwoven'''.

http://animalsciences.missouri.edu/courses/4314/microscope_slides/ampulla.jpg

*Serosa:
*The serosa is a '''true serosa''' because it is lined with mesothelium.

http://instruction.cvhs.okstate.edu/histology/fr/images/OviductBp12.jpg

http://neuromedia.neurobio.ucla.edu/campbell/female/wp_images/56_oviduct_LP.gif

http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/Oviductlx1XL.jpg

===The uterus===

====Layers of the uterine wall====
*Like the oviducts and other epithelial tracts, there are '''four tissue-type layers to the uterus''' which make up '''three functional layers''' of the

uterus.
*The epimetrium is composed of serosa and adventitia and is a form of '''mesothelium''' as one would expect to cover surface of organs that faces the inside

of the abdomenal cavity.

*Note that the cervix is histologically distinct from the rest of the uterus; we will revisit this.

http://people.fmarion.edu/tbarbeau/oviduct_histo.jpg

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/1%20uterus.jpg

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/Uterues%202.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab28/IMAGES/FEML20.JPG

http://www.siumed.edu/~dking2/erg/images/RE018b.jpg

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/uterus1.jpg

http://www.ouhsc.edu/histology/Glass%20slides/21_01.jpg

===The uterine cycle===
*From [http://editthis.info/iusmphysiology/?title=Female_reproductive_physiology&section=20#Mentrual_cycle physio notes]:
*The '''proliferative stage''' is characterized by '''endometrium hypertrophy''' and formation of '''spiral arteries'''.
**So as the ovary is maturing its follicle, the uterus is regenerating it's surface (where the egg will implant) and increasing vascular access to the

surface.
*The '''secretory stage''' is characterized by '''coiling of glands''', '''secretion of mucus''', '''tortuous arteries''', and '''peak thickness of the

endometrium'''.
**So, as the ovary has shed an ovum and is now increasing hormone production via the corpus luteum, the uterus is using glands and arteries of the uterus to

modify the uterine microenvironment to the optimal conditions for egg implantation.
*The '''ischemic stage''' is characterized by '''arterial constriction''', '''decreased blood flow''', and '''increased prostaglandins'''.
**So as the ovary has reached its lowest levels of hormone production, the uterus is decreasing nutrition to the endometrium and allowing the mucosa to

undergo necrosis by ischemia.
*The '''menstrual stage''' is characterized by '''desquamation of the endometrium'''.
**So as the ovary has reached its lowest levels of hormone production, the uterus is shedding its endometrium.

====Uterine vasculature====
*The uterus is supplied by '''arcuate arteries that run along the myometrium''' layer and by '''radial arteries that cross into the endometrium'''.
*The radial arteries give off '''straight (basal) arteries that supply the endometrium basalis'''.
**Note that the endometrium is divided into two layers: the '''endometrium basalis''' is a constant, mostly unchanging layer while the '''endometrium

functionalis''' cycles through generation (proliferation) and shedding.
**'''There is no structural marker to distinguish between the basalis and the functionalis of the endometrium'''.
*'''Spiral (coiled) arteries''' are heavily muscular, generated during the endometrial cycle, and bridge the radial arteries into the endometrial

functionalis.
**Of special note are the vascular structures nearest the lumen of the uterus called '''lacunae'''.

http://upload.wikimedia.org/wikipedia/commons/thumb/0/08/Uterine_arterial_vasculature.svg/220px-Uterine_arterial_vasculature.svg.png

====Uterine endometrium====
*The endometrial mucosa contains '''uterine glands'''.
**Uterine glands are tubular with many branches.
**Uterine glands contain both '''ciliated''' and '''non-ciliated''' cells.

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection3/FemaleRepTract03_files/image006.jpg

====Histological changes in the uterine cycle====
*The phases are divided over approximately 28 days: menstruation (days 1-5), proliferation (6-15), secretion (16-17), ischmia (18-28).

*Menstruation:
**Note that '''the base of the uterine glands''' remain visible in the endometrium basalis.
**http://upload.wikimedia.org/wikipedia/commons/thumb/0/08/Uterine_arterial_vasculature.svg/220px-Uterine_arterial_vasculature.svg.png

*Proliferative stage:
**The proliferative stage is '''driven by estrogen''' produced by the developing follicle.
**In addition to gland coiling, '''spiral arteries develop''' in the thickening endometrium.
**'''Cells of the proliferative endometrium accumulate glycogen'''.

*Secretory stage:
**The secretory stage is '''driven by progesterone''' from the corpus luteum.
**The secretory stage is characterized by '''release of glycoprotein-rich products''', '''swelling and torture''' of the glands and spiral arteries, and

'''accumulation of fluid in the stroma''' of the endometrium.

*Ischemia:
**The ischemic stage is characterized by '''constriction of the coiled arteries''', '''stromal fluid loss''', and '''lymphocyte / macrophage cell

invasion'''.
***When the corpus luteum degenerates and progesterone levels drop, local prostaglandins are released into the endometrium, the vessels constrict, and blood

flow is arrested causing ischemia.
**The coiled arteries dilate and constrict intermittently which causes ischemia, cell lysis, a weakened stroma, bursting vessles, and debridement of the

functionalis.
***The arteries both restrict oxygen (constriction) to cause cell death but also to flush away the dead tissue (dilation).

====Uterine cervix====
*As mentioned before, '''the cervix is histologically distinct''' from the rest of the uterus.

*The cervical myometrium:
**'''The cervical myometrium has '''less smooth muscle''' and '''abundant collagenous connective tissue with elastic fibers'''.

*The cervical endometrium:
**The cervical endometrium has '''denser stroma''', '''simple columnar epithelium''', '''branched, dilated, cyst-forming glands''', and longitudinal mucosal

folds called '''plicae''' (plicae palmatae).
***Cervical glands can form cysts called '''Nabothian cysts'''.

*The cervical mucus:
**Mid way through the cycle (think ovulation and sperm-friend environment) the mucus is '''watery''', contain '''lysozyme''' (bacterioalcidal), and promotes

sperm motility.
***This sperm-friendly mucus is '''estrogen-stimulated'''.
**Late in the uterine cycle (think corpus luteum and potential implantation) the mucus is viscous and '''progesterone-stimulated'''.
**During pregnancy the mucus is particularly thick (think lots of progesterone) and thus protective of the fetus.
***One may look for the loss of this dense mucus plug as a sign that parturition is commencing.

http://www.siumed.edu/~dking2/erg/images/RE052b.jpg

http://www.netterimages.com/images/vtn/000/000/007/7987-150x150.jpg

http://www.gfmer.ch/Books/Cervical_cancer_modules/Images/MI7.jpg

http://www.fpnotebook.com/_media/GynCervicalColposcopyAcetowhite1.jpg

http://missinglink.ucsf.edu/lm/IDS_106_LowerGI/IDS_images_downsized/fig10.jpg

=====The ectocervix=====
*The ectocervix is also called the '''portio vaginalis'''.
*At the ectocervix the '''epithelium changes from columnar (cervix) to stratified squamous (vagina)''' abruptly.
*Normal ecotcervix:
**http://pathweb.uchc.edu/eAtlas/Images/GYN/5764b.gif http://pathweb.uchc.edu/eAtlas/Images/GYN/5766b.gif
*http://www.nature.com/nri/journal/v8/n6/images/nri2302-f1.jpg
*http://www.arabicobgyn.net/doc/CERVIX_files/image010.gif
*http://www.path.cam.ac.uk/Abnormal/NP_Neoplasia/ME_Metaplasia/CX_Cervix/A_NP_ME_CX_01small.jpg

===Vagina===
*The mucosa is characterized by stratified, squamous, non-keratinized epithelium.
**The epithelial cells of the vagina--like those of the uterus--accumulate glycogen upon estrogen signaling.
*The vaginal lamina propria has '''no glands''', patches of '''lymphocytes''', and can have folds.
**Recall, however, that the uterus does have glands in the lamina propria.
*The vaginal muscularis has '''interlacing bundles of smooth muscle'''.

http://www.lab.anhb.uwa.edu.au/mb140/CorePages/FemaleRepro/Images/vag02he.jpg

http://www.ansci.wisc.edu/jjp1/ansci_repro/lec/lec1/female_images/images_label/vagina(l).jpg

http://www.ouhsc.edu/histology/Glass%20slides/22_05.jpg

http://www.ouhsc.edu/histology/Glass%20slides/23_04.jpg

===Mammary glands===
*The mammary glands are made of a compound tubuloalveolar system; that is, there are alveoli that take part in the secretory component and there are ducts

that take part in the transport component.
**A group of about 20 glands forms a '''mammary lobule'''.
*Secretory component:
**Milk is generated by '''cuboidal epithelial cells''' arranged in '''alveoli'''.
**The '''myoepithelial cells arise from the cuboidal epithelial cells'''.
**Plasma cells are found in and around the alveoli in order to '''generate IgA'''.
*Mammary ducts:
**The epithelium that lines the ductule system is '''stratified cuboidal'''.
**There is a significant amount of '''smooth muscle between the ducts and sinuses'''.
**Most breast cancers arise from lactiferous duct cells.

https://lh3.googleusercontent.com/_WdFQawAlzZM/TW_UdyeIT0I/AAAAAAAAAoA/pvQX_ngLS0M/s800/F22_27.jpg

http://www.nature.com/nrc/journal/v2/n2/images/nrc721-f1.jpg

http://www.genericlook.com/img/uploads/anatomy/mammary-glands.jpg

http://neuromedia.neurobio.ucla.edu/campbell/skin/wp_images/161_myoepithelial.gif

http://www.breast-cancer.ca/images/breast-myoepithelial-cells.jpg

http://neuromedia.neurobio.ucla.edu/campbell/glands/wp_images/myoepithelial%20cells.jpg

http://img.medscape.com/pi/emed/ckb/pediatrics_cardiac/1331339-1331345-1835675-1835738.jpg

====Mammary glands at puberty====
*When '''estrogen''' increases at puberty ('''and prolactin is present'''), '''alveolar buds develop and regress''' with each ovarian cycle.

====Mammary glands in pregnancy====
*Upon pregnancy, estrogen is found at high levels '''along with prolactin, placental lactogen, and progesterone''' and therefore the alveolar ducts and

alveoli fully develop.
*'''Lactogenesis is regulated by estrogen, progesterone, and prolactin'''.
**This makes sense because estrogen and progesterone increase throughout pregnancy and once progesterone and estrogen drop (at parturition), prolactin has

its most potent effect.
*'''Galactogenesis is maintained by prolactin and oxytocin'''.

http://www.as.miami.edu/chemistry/2086/chap28/NewChap28-Female_files/image010.jpg

https://lh4.googleusercontent.com/_WdFQawAlzZM/TaOd4WAHBbI/AAAAAAAAAuc/9Hh5a4tSLKE/s800/mammary_gland_comparison.jpg

====Breast milk====
*The first milk generated is called colostrum; colostrum is '''lactoprotein- and immunoglobulin- rich''' and '''lipid-deficient'''.
*Lactation can generate 1100 to 2100 ml every day.
**Note that physio said 800-1200 ml / day.
*These cuboidal epithelial cells use several secretion mechanisms to release their products.
**'''Merocrine secretion''' is used to secrete casein, alpha-lactalbumin, and PTH-RP (protein, basically).
**'''Apocrine secretion''' is used to secret TAGs and cholesterol.
**'''Exocytosis''' is used to secrete lactose.
**'''Transcytosis''' (from adjacent plasma cells) is used to secrete dimeric IgA.

====Regulation of milk let-down====
*Note that '''afferent CNS signals also stimulate dopamine inhibition''' such that '''prolactin is increased''' which stimulates the cuboidal epithelial

cells of the alveoli to increase milk production.
*Note that '''multiple neuroendocrine factors''' have been found besides oxytocin to '''relax the smooth muscle sphincter''' between the lactiferous ducts

and the lactiferous sinuses.

===Summary===
*Estrogens increase as the follicle develops and:
**inhibit FSH at the pituitary
**stimulate LH at the pituitary
*LH promotes corpus luteum formation
*Corpus luteum produces progesterone and estrogen
**Estrogen causes uterine proliferation phase
**Progesterone causes uterine secretory phase
*Progesterone inhibits LH

==Male reproductive==

===Anatomy review===
*The '''mediastinum testis''' is where the vessels (blood and lymphatics), nerves, and efferent duct enter and exit the testis.
**Note that the mediastinum testis is connective tissue while rete testis is a collecting tubule tissue.
**The '''tunica propria''' is the outer wall of the seminiferous tubule and is made of '''smooth muscle and fibroblasts'''.

===Seminiferous epithelium===

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection3/TestesandSperm03_files/image002.jpg

===Spermatogenesis===
*Primary spermatocytes are in the prophase of meiosis 1 and stick around for 20 days.
*Secondary spermatocytes are relatively short-lived.

*Cells of the basal compartment: type A and type B spermatogonia, primary spermato'''cytes'''
*Cells of the adlumenal compartment: secondary spermatocytes, spermatids, spermatozoa

*Cells and processes: type A spermatogonia undergo mitosis to become ... type B spermatogonia undergo mitosis (and differentiation) to become ... primary

spermatocytes undergo meiosis 1 ... secondary spermatocytes undergo meiosis 2 ... spermatids undergo morphologic modification (differentiation) ...

spermatozoa.
**'''Spermatocytogenesis''' includes all the steps that generate an increasing number of cells (that is, type A spermatogonia through generation of secondary

spermatocytes); this makes sense because of the name "cyto" = cell and genesis = "origin of".
**'''Spermiogenesis''' is the converse of spermatocytogenesis: spermeiogenesis is the maturation of existing cells into spermatozoa (from the secondary

spermatocyte stage to the spermatozoa stage).

http://image.wistatutor.com/content/reproduction-in-animals/spermatogenesis-and-spermiogenesis-stages.jpeg

http://image.wistatutor.com/content/reproduction-in-animals/spermatogenesis-spermiogenesis-process.jpeg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab27/IMAGES/MREPL08.JPG

====Mitosis and Meiosis====

====Spermiogenesis====
*Spermiogenesis is characterized by morphological changes to the spermatid, that is the specialization / differentiation of the spermatid into the

spermatozoa:

*Golgi phase:
**The enzymes like hyaluronidase and trypsin-like protease accumulate at one pole of the nucleus in a vesicle (which will become the acrosome).

*Acrosomal phase:
**The cell '''rotates such that the axoneme faces the lumen'''.

*Maturation phase:
**The maturation phase is characterized by motile apparatus development and the capacity to fertilize.
**Note that '''during the maturation phase, the spermatids are not yet motile or fertile'''.

http://www.ccs.k12.in.us/chsBS/kons/kons/images/spermiogenesis.jpg

===Sertoli cells===
*Sertoli cells are characterized by being '''tall, columnar''' epithelial cells with a '''large, indented euchromatic nucleus''', and lots of eosinophilic

cytoplasm.
*Neighboring Sertoli cells within a region have '''gap junctions which suggest that Sertoli cells are coordinated within their region'''.

====Blood testis barrier====
*Sertoli cells of the seminiferous epithelium form tight junctions between one another to keep immunoglobulins in the blood from entering the lumen of the

tubule.
**Note that these '''tight junctions of the Sertoli cells are on the ''lumenal'' side of the spermatogonia'''.
**These tight junctions define the two compartments: basal compartment and adlumenal compartment.

====Sertoli function stimulated by FSH====
*Recall that the anterior pituitary releases FSH which binds to the FSH receptor on Sertoli cells.
*FSH signaling on Sertoli cells causes phagocytic activity and production of several secretions.
*Secretions of the Sertoli cells:
**Activin and Inhibin: stimulate and inhibit the anterior pituitary cells to release FSH.
**Androgen binding protein (ABP): secreted into the lumen of the seminiferous tubule, binds up and concentrates testosterone.
**Tubular fluid: lubrication.

===Leydig cells===
*Note that '''Leydig cells do not secrete activin or inhibin'''.
*Leydig cells are found in clusters in the '''peritubular interstitium''' of the testis, between the seminiferous tubules.
**Recall that Leydig cells are often found near capillaries.
*Leydig cells are characterized by eiosinophilicism, lots of sER, mt with tubular cristae, and '''a lack of secretory vesicles'''.
**Regarding lots of sER, recall that steroids are generated in sER.
**Regarding a lack of secretory vesicles recall that steroids can pass directly through the membrane and therefore need not vesicular secretion.
**By transmission EM, one can also discern '''crystalline inclusions'''.

*Leydig cells are "transiently" active during development and then initiate full activity at puberty.

===Segments of the male reproductive tract===
*Seminiferous tubules -> tubuli recti (straight tubules) -> rete testis -> efferent ductules -> epididymal ducts -> ductus deferens (vas deferens) ->

ejaculatory duct -> prostatic uretral -> membraneous urethra -> penile urethra.

Where do basal cells and principal cells start?

*Straight tubule (tubuli recti)
**Contributes to fluid
**Cuboidal to columnar
**'''Contains Sertoli cells'''

*Rete testis
**Contributues to fluid
**Has an '''irregular epithelial morphology''': squamous, cuboidal, columnar.
**Has a '''fibrous stroma'''

*Efferent ductule
**Like the rete testis, the efferent ductule has an irregular epithelial morphology and also has '''ciliated, pseudostratified cells'''.
***These ciliated pseudostratified cells are called '''principal cells''' and are found as clusters of columnar cells surrounded by short cells.
***These cells are '''the only ciliated cells of the male genital tract'''; it even makes a bit of sense that these are ciliated because they are passing

through a sturdy connective tissue structure.

*Ductus epididymis
**The ductus epididymis is characterized by an pseudostratifed columnar epithelium, '''stereocilia''', and a '''prominent muscularis layer'''.
**'''Basal cells are regenerative.'''
**'''Principal cells are secretory / absorptive.'''
**The ductus epididymis has a prominent muscularis layer that thickens distally and changes from just a circular layer to an '''inner circular and outer

longitudinal layer'''.
**The functions of the ductus epididymis: absorb 90% of the tubular fluid, secrete factors that mature and capacitate sperm, and phagocytize cellular debris.

*Ductus deferens (vas deferens)
**The ductus deferens is characterized by a pseudostratified columnar epithelium, '''abundant sympathetic innervation''', and '''three layers to the

muscularis'''.
**The ductus deferens is pseudostratified (like the efferent ductule and ductus epididymis) and has stereocilia (like the ductus epididymis).
**The muscularis has now added an inner longitudinal muscle layer to the ductus epididymis's inner circular and outer longitudinal.
**The sympathetic innervation will be important for ejaculation which is facilitated by contraction of the ductus deferens's muscularis.
***Recall that Point and Shooting require Parasympathetic and Sympathetic innervation.

*Ejaculatory duct

*Membranous urethra
**The membranous urethra is characterized by a '''pseudostratified epithelium that transitions to a stratified columnar epithelium.'''

*Penile urethra
**The penile urethra is characterized by a '''pseudostratified epithelium that transitions to a stratified columnar epithelium''', perhaps continuing on to

'''stratified squamous epithelium at the top'''.
**The penile urethra is also characterized by the presence of '''urethral glands''' which are clusters of mucus cells in the mucosa.

{| border="1"
|-
! Section
! Epithelium
! Appendages
! Muscularis
|-
| Seminiferous tubule
| stratified
| none
| none
|-
| Tubuli recti
| cuboidal -> columnar
| none
| none
|-
| Rete testis
| irregular: squamous, cuboidal, columnar
| none
| none
|-
| Efferent ductule
| pseudostratified
| cilia
| none
|-
| Ductus epididymis
| pseudostratified
| sterocilia
| circular -> circular (inner) + longitudinal
|-
| Ductus deferens
| pseudostratified columnar
| stereocilia
| longit (inner) + circular + longit
|-
| Ejaculatory duct
| pseudostratified columnar
| ?
| ?
|-
| Prostatic urethra
| pseudostratified -> simple columnar
|
|
|-
| Membranous urethra
| pseudostratified -> stratified columnar
| none
| longit (inner) + circular + longit
|-
| Penile urethra
| pseudostratified -> stratified columnar -> stratified squamous
| none
| longit (inner) + circular + longit
|}

===Accessory glands of the male reproductive tract===

====Seminal vesicles====
*Seminal secretions are rich in fructose (for energy), prostaglandins, amino acids, and ascorbic acid.
*The seminal vesicle has plenty of '''smooth muscle''' with which to force this secretion out into the ejaculatory duct.
*Seminal vesicle function and growth is mediated by testosterone.
*The vesicles are blind-ended pouches near the prostate and ductus deferens.
*'''Seminal vesicles are lined with pseudostratified columnar epithelium'''.
**This makes sense because they pump semen out into the GU tract at the ductus deferens and ejaculatory duct, both of which are pseudostratified.
*The seminal vesicles have '''mucosal arches''' which are highly folded, convoluted walls.

====Prostate====
*The prostate generates a secretion that becomes part of the semen and '''serves to condition the environment of the famale GU tract'''.
*The '''fribromuscular stroma''' surrounding the prostate is important for proper discharge of prostatic secretions during ejaculation.
*Zinc inhibits macrophage activity.
*Fibrinolysin inhibits clot formation in the uterus.
*The prostate as a gland has alveoli connected via tubules; the tubules converge to generate a '''group of ducts''' that dump into the '''urethral crest'''.
**The urethral crest receives the ejaculatory ducts and becomes the prostatic urethra.
**The epithelium within the gland is irregular: pseudostratified to simple columnar.
*'''Corpora amylacea''' is a concentration of glycoprotein-rich secretion in the lumen of the gland that stains eosinophilic (because of the "protein-rich"

part).

*The prostate has three concentric-like zones: central zone, transitional zone, and peripheral zone.
*The '''central zone''' of the prostate is the most medial and contains primarily '''periurethral mucosal glands'''.
**The central zone often stains the lightest of the zones.
*The '''transitional zone''' of the prostate is the middle zone and contains '''periurethral submucosal glands'''.
**Note that the '''central and transitional zones''' are most commonly associated with '''benign prostatic hypertrophy (BPH)'''.
*The '''peripheral zone''' of the prostate is the outer zone, contains the '''main glands''', is called the '''prostate proper''', and is commonly involved

with '''malignancies'''.
**The peripheral zone is often involved with '''prostate cancer'''.

====Bulbourethral glands====
*The bulbourethral glands produce a secretion for lubricating the male GU tract for ejaculation.
*The secretion of the bulburethral gland is clear and viscous.

===Ejaculation sequence===
*Ejaculation has a particular series of events regarding all these secretions:
**Bulbourethral glands discharge to lubricate.
**Prostate releases contents (via contraction of the fibromuscular stroma).
***Recall that the prostate's secretions serve to condition the female GU tract.
**The ductus deferens receives sympathetic stimulation to contract its muscularis (1->2 layers), thus pushing spermatozoa into the urethra.
**Seminal vesicles discharge their contents thus clearing the urethra by pushing semen distally.

*ID straight tubules by the presence of Sertoli cells.
*Ductus epididymis has very tall cells with cilia.
*Ductus deferens ID by stereocilia and three layers of muscle.
*Seminal gland: mucosal arches
*Prostate is ID'd by '''corpora amylacea''' (a concentration of glycoprotein-rich secretion in the lumen of the gland that stains eosinophilic).

==Skin==

===Describe the basic histological structure of the skin===

http://www.lab.anhb.uwa.edu.au/mb140/corepages/integumentary/Images/skthick0021he.jpg

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%202%20Review/epidermal_ridges1.gif

===Identify the cell layers that constitute the epidermis===
*Also, the granulosa and corenum layers are thicker in "thick skin".

http://www.greenfoodsonline.co.nz/blog/wp-content/uploads/2009/07/epidermal-layers.jpg

http://faculty.stcc.edu/AandP/AP/imagesAP1/skin/skin.jpg

====Stratum basale====
*The cells of the basal layer are connected to the basement membrane via '''hemidesmosomes'''.

http://employee.lsc.edu/faculty/BrianBich/Picture%20Library/Anat-Phys%20I%20(Biol%201140)/Integument/Thick%20Skin%20-%20Tutorial/F%20-%20Thick%20Skin%2040X-

3-Epidermal%20Layers.jpg

====Stratum spinosa====

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Integumentarysystem03_files/image004.jpg

https://lcsdanatomyphysiology.wikispaces.com/file/view/epidermis.png/194354678/epidermis.png

http://lecannabiculteur.free.fr/SITES/UNIV%20W.AUSTRALIA/mb140/CorePages/Integumentary/Images/skn40he.jpg

====Stratum granulosmum====
*The granule-containing cells of the granulosum contain '''filaggrin, and intermediat filaments''' that help to form the '''tonofibrils''' along with

'''keratin'''.
**Note that these granules are called '''keratohyline granules'''.
**Kertohyline granules have no membrane.
*The cells of the granulosum are flattened polygonal cells--found in 3 to 5 layers.
**Just like "lamellae" in chloroblasts, lamellar granules have a sort of stacked-bags look
*Labellar graunules cannot be seen in light microscopy.
**http://www.bioone.org/na101/home/literatum/publisher/bioone/journals/content/bire/2000/00063363-63.6/biolreprod63.6.1706/production/images/small/i0006-

3363-63-6-1706-f06.gif
**http://biologiedelapeau.fr/IMG/jpg/lamellar-granules-3web.jpg

http://bestofbothworldsaz.com/wp-content/uploads/2010/09/SkinLayers.jpg

http://www.dermpedia.org/files/u49/Epidermolytic_hyperkeratosis_stp5.jpg

http://www.virtualmedicalcentre.com/uploads/VMC/Anatomy/oral_mucosa_450.jpg

http://www.anatomyatlases.org/MicroscopicAnatomy/Images/plate136.jpg

====Stratum lucidum====
*The lucidum (ironically) stains darkly.

http://ouhsc.edu/histology/Glass%20slides/43_09.jpg

====Stratum corneum====

http://employee.lsc.edu/faculty/BrianBich/Picture%20Library/Anat-Phys%20I%20(Biol%201140)/Integument/Thick%20Skin%20-%20Tutorial/D%20-%20Thick%20Skin%2040X-

1-Epidermal%20Layers.JPG

====Dermo-epidermal junction====
*Recall, too, that the epidermal cells of the basal layer are connected to the basement membrane via hemidesmosomes.
*The dermis contains lots of '''type 4 collagen'''.
*The superficial aspect of the dermis that is attached to the basement membrane of the epidermis is the '''lamina densa'''.
*The lamina densa of the dermis and the basement membrane of the epidermis are connected via '''anchoring filaments''' and '''anchoring fibrils'''.
**Note that '''anchoring filaments are composed of type 7 collagen'''.

https://steinbachs.org/download/attachments/4686497/Fig18-3c.jpg

===Describe the cellular components of the epidermis and their functions===
*There are four major cells of the epidermis: keratinocytes, melanocytes, langerhan cells, and merkel cells.

https://lh6.googleusercontent.com/_WdFQawAlzZM/TaRKusxrDOI/AAAAAAAAAu4/yid3LHxB7Pw/s800/epidermal_cells.jpg

====Keratinocytes====

http://www.nanogen.org/en/images/nano-skincell-life.gif

====Melanocytes====
*Melanocytes are '''derived from neural crest cells''' and function to generate the pigment melanin which protects cells from UV damage.
*Melanosomes are said to "mature" as they are produced; they turn from a light, circular shape to a dense cucumber shape.

http://faculty.une.edu/com/abell/histo/thickskin1w.jpg

http://autoimmune.pathology.jhmi.edu/images/Skin2.jpg

http://www.ccs.k12.in.us/chsBS/kons/kons/images/Skin_tws_16_02.jpg

http://skinipedia.org/images/photos/melanocyte2.jpg

http://www.lab.anhb.uwa.edu.au/mb140/corepages/integumentary/Images/labmi040he.jpg

http://www.ratbehavior.org/images/MyosinTravelBig.jpg

http://www.nature.com/nrm/journal/v8/n10/images/nrm2258-f4.jpg

====Langerhans cells====
*Langerhans cells reside primarily in the '''spinosum''' layer (think "spines and chinese are for killing bad guys!''').

http://www.technion.ac.il/~mdcourse/274203/slides/Skin/6-Langerhans%20Cells.jpg

http://www.nature.com/nm/journal/v13/n3/images/nm0307-245-F2.gif

====Merkel cells====
*Merkel cells (like melanocytes) are found primarily in the basal layer, which makes sense because they are a sensation cell that needs to be near a nerve

ending.
**Note that '''Merkel cells are found primarily in thick skin''' where touch needs to be highly sensitive.
*Merkel cells, along with the '''expanded terminal bulb''' of afferent, myelinated nerves, form the '''Merkel's corpuscle''' which detects touch as a

'''mechanoreceptor'''.
*The Merkel cells contain dense-cored '''neurotransmitter granules'''.

http://neuromedia.neurobio.ucla.edu/campbell/skin/wp_images/cell%20types.jpg

===Describe the structural organization of the dermis===

====Papillary layer of the dermis====
*Connective tissue of the papillary layer is composed of '''type 1 collagen''', '''type 2 collagen''', and '''elastic fibers.

====Reticular layer of the dermis====
*The reticular layer is composed of '''type 1 collagen''' and '''regularly oriented elastic fibers (called Langer's lines)'''.

http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology%20Glossary/Glossary%20Histo%20Images/Papillary_vs_Reticular_Dermis_10x-208.jpg

http://bestofbothworldsaz.com/wp-content/uploads/2010/09/SkinLayers.jpg

http://www.biology-online.org/user_files/Image/Anatomy/AN-fibroblastF02.gif

http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/dermis1.jpg

http://www.bu.edu/histology/i/08203loa.jpg

http://farm4.static.flickr.com/3412/3195805407_be3ba25e62_o.jpg

===Identify other structures in the skin===

====Vessels====

http://www.netterimages.com/images/vpv/000/000/056/56826-0550x0475.jpg

http://www.netterimages.com/images/vpv/000/000/056/56826-0550x0475.jpg

====Sensory receptors====
*There are four types of sensory receptors in the integumentary system (skin): free nerve endings, pacinian corpuscles, meissner's corpuscles, and ruffini's

corpuscles.

=====Free nerve endings=====
*Free nerve endings are found in the '''stratum granulosum''' and detect '''fine touch, heat, and cold'''.
*http://library.thinkquest.org/05aug/00386/touch/freenerveendings.gif
*http://webanatomy.net/histology/neural/free_nerves.jpg

=====Pacinian corpuscles=====
*Pacinian corpuscles are nerve endings surrounded by an oval encapsulation of connective tissue in the '''deeper dermis and hypodermis'''.
*Think '''maraca shaped and all that vibration!'''
*http://library.thinkquest.org/05aug/00386/touch/paciniancorpuscule.gif
*http://www.siumed.edu/~dking2/intro/images/IN039b.jpg
*http://kentsimmons.uwinnipeg.ca/cm1504/15lab42006/lb4pg9_files/image012.jpg
*http://www.esg.montana.edu/esg/kla/ta/pacinian.jpg
*http://download.videohelp.com/vitualis/med/pacinian_corpuscle.jpg
*http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_&_Physiology/A&P202/Special_Senses/Pacinian_corpuscles_PC271521lbd.JPG
*http://www.sci.uidaho.edu/med532/images/receptor/pac_corp2.jpg

=====Meissner's corpuscles=====
*Meissner's corpuscles are found in the papillary layer of the dermis and are sensitive to '''low frequency stimuli'''.
**Doesn't "meissner" sound like an old miser with a low, grumpy voice?
*Meissner's corpuscles are shaped like tapered '''m'''itochondria and are oriented perpendicular to the skin.
*http://library.thinkquest.org/05aug/00386/touch/meissnercorpuscule.gif
*http://www.starsandseas.com/SAS_Images/SAS_Physiol_Images/SAS%20neuropics/Neurons_02.jpg
*http://www.siumed.edu/~dking2/bluehist/BH011b.jpg
*http://www.siumed.edu/~dking2/intro/images/IN038b.jpg
*http://www.cytochemistry.net/microanatomy/nerve/nerve12.jpg
*http://cmdi.medicine.dal.ca/Anat5217/Lab9/26LHMC.JPG
*http://ouhsc.edu/histology/Glass%20slides/101_04.jpg
*http://webanatomy.net/histology/neural/meissners.jpg
*http://kcfac.kilgore.cc.tx.us/mobleypageap2/nerve%20tisues/Meissner%27s%20corpuscle%20400x%20fireworks.jpg

=====Ruffini's corpuscles=====
*Ruffini's corpuscles are simple mechanoreceptors and have an "elongated fusiform shape".
*http://library.thinkquest.org/05aug/00386/touch/ruffiniending.gif

=====Sensory receptor images=====
http://www.neurobiography.info/teaching/images/somatosensory/cutaneous_receptors_hairy_vs_nonhairy_1.gif

http://iupucbio2.iupui.edu/anatomy/images/Chapt18/FG18_03d-f.jpg

http://alexandria.healthlibrary.ca/documents/notes/bom/unit_6/unit6.images/peripheral%20mech%20fig%201.jpg

http://www.exploringnature.org/graphics/anatomy/sensory%20organs.jpg

http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate123.jpg

http://www.karger.com/gazette/67/Elsner/images/skin.gif

http://www.healthyheating.com/Thermal_Comfort_Working_Copy/Images/Nerve_endings_labeled.gif

====Hair follicles====
*At the hair follicle a specialized layer called the '''glassy membrane''' (a type of basement membrane that is thickened and keratinized) separates the

epidermis and the dermis.
*During hair growth, the follicle has a bulbous end at the deepest part.

*Hair has three layers (from outside in): cuticle, cortex, and medulla.
**The '''cuticle''' is the outer most and is comprised of '''squamous cells'''.
**The '''cortex''' contains '''cuboidal cells''' that differentiate into '''keratinized cells'''.
**The '''medulla''' contains large cells with '''vacuoles''' that are '''moderately keratinized'''.

*Sebum is released into the '''infundibulum''' which is a '''pilosebaceous canal''' that surrounds the base of the growing hair.
**http://www.follicle.com/img/follicle.jpg

http://elin.ttu.ee/mesel/Study/Subjects/0070BME/Content/BioElect/ProcPhen/7_kude_nahk_172-1x-Hair_follicle_labelled.jpg

http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/hair4F.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab15/IMAGES/INTEGL16.jpg

http://www.spencerclinic.co.uk/images/hair_pic2_large.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab15/IMAGES/DEEP%20HAIR%20FOLLICLE.jpg

http://amakabeautycare.files.wordpress.com/2010/03/hair-follicle-2.gif

http://www.raising-redheads.com/images/HairFollicleWikip.png

http://www.nature.com/nbt/journal/v18/n1/images/nbt0100_20_F1.gif

=====Phases of hair growth=====
*http://www.body-beauty-shop.com/images/hair-growth-cycle.jpg
*https://lh6.googleusercontent.com/_WdFQawAlzZM/TaRf2b28PvI/AAAAAAAAAvI/mWnIfw18-Bg/s800/F1.large.jpg

====Nails====
*The nail plate sit in the '''nail bed''' which is formed by the stratum basale and spinosum.

http://fungusfacts.com/wp-content/uploads/2009/10/nail-anatomy-diagram-cross-section.jpg

http://eulep.pdn.cam.ac.uk/~skinbase/Annotated_anatomy_of_the_mouse_nail/nail_labelled.jpg

http://classroom.sdmesa.edu/anatomy/Histologyphotos/Integument/Nail%201.jpg

http://www.footdoc.ca/Websit1.jpg

http://www.adiosnailfungus.com/images/anatomy_toenail.jpg

====Glands====

http://www.transtutors.com/Uploadfile/CMS_Images/21926_MODE-OF-SECRETION.JPG

http://medicalsolutions.medi-health.info/pilsinl/348.gif

=====Sebaceous glands=====

http://blog.dearbornschools.org/renkom/files/2010/12/sebaceous-gland.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab4/IMAGES/SEBACEOUS%20GLAND%20LABELED%20copy.JPG

http://www.nku.edu/~dempseyd/sebaceous%20gland%202%20good.jpg

http://www.pgbeautygroomingscience.com/assets/images/wosc/Chapter%201/Special%20Skin%202.jpg

http://www.lab.anhb.uwa.edu.au/mb140/corepages/integumentary/Images/sebaceous011he.jpg

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%202%20Review/ceruminous_gland.gif

=====Sweat glands=====

{|border="1"
|-
!Attribute
!Merocrine
!Apocrine
|-
|Secretion method
|Merocrine
|Apocrine '''and merocrine'''
|-
|Distribution
|Widely distributed
|Axillary and perineal regions only
|-
|Lumen size
|Small lumen
|Large lumen
|-
|Epithelial type
|Stratified cuboidal
|Simple cuboidal
|-
|Innervation
|Cholinergic fibers (ach)
|Adrenergic (cats)
|}

*Merocrine (eccrine):
**http://2.bp.blogspot.com/_o-Hb5F-QYCA/Sg1vjbjJ_pI/AAAAAAAABEs/ObmtIy1juXY/s400/180X10merocrine_sweat_gland.jpg
**http://www.technion.ac.il/~mdcourse/274203/slides/Skin/8-Eccrine%20Sweat%20Gland.jpg

*Apocrine:
**http://faculty.une.edu/com/abell/histo/apocrinesgw.jpg
**http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/skinglands3F.jpg

*Visual differentiation:
**Lumen size: small = merocirne, large = apocrine
**Density: denser = merocrine, lighter = apocrine
**Surrounding cells: myoepithelial cells surround merocrine to help secrete, apocrine don't necessarily have surrounding cells.

===Understand the mechanism of skin repair===

http://journals.cambridge.org/fulltext_content/ERM/ERM5_08/S1462399403005817sup005.gif

===Describe the histological findings in common skin diseases===

====Blistering====
*Abnormalities at the '''epidermis-dermis junction''' are called '''bullous pemphigoid'''.
**http://www.dermpedia.org/files/images/Bullous_pemphigoid_3.jpg
*Abnormalities of intercellular junctions are called '''pemphigus'''.
**http://library.med.utah.edu/kw/derm/mml/24820016.jpg

====Psoraisis====
*Psoriasis occurs when cells of the basal and spinosum layers demonstrate '''excessive proliferation''' and decreased cycle time which leads to '''increased

thickness'''.
*One can identify psoriasis by the presence of '''nuclei in the stratum corneum'''; this finding is called '''parakeratosis'''.

http://www.drmihm.com/pictures/ACF1E7.jpg

http://www.webpathology.com/slides/slides/ExtGenitalia_Pagets1.jpg

http://dermatology.cdlib.org/126/unknown/eyelid/2.jpg

====Skin cancer====

http://www.aafp.org/afp/2004/1015/afp20041015p1481-f1.gif

=====Basal cell carcinoma=====
http://skincancer-fact.com/wp-content/uploads/2009/10/Basal_cell_carcinoma_-skin_cancer-picture.jpg

http://www.orlandoskindoc.com/Basal-cell-carcinoma-large.jpg

http://www.trihealth.com/ser/cancer/images/Basal_cell_carcinoma.jpg

http://www.healthpm.com/wp-content/uploads/2010/09/basal_cell_carcinoma.jpg

http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology%20Glossary/Glossary%20Histo%20Images/basal_cell_carcinoma_high_power.jpg

=====Squamous cell carcinoma=====
http://www.medicalook.com/diseases_images/squamous_cell_carcinoma.jpg

http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology%20Glossary/Glossary%20Histo%20Images/squamous_cell_carcinoma_in_situ_high_power.jpg

=====Malignant melanoma=====

http://www.prlog.org/10263280-malignant-melanoma.jpg

http://sunsafekids.tripod.com/sitebuildercontent/sitebuilderpictures/melanomas.jpg

http://www.nature.com/modpathol/journal/v18/n8/images/3800395f1.jpg

http://rad.usuhs.mil/derm/lecture_notes/Images/melanoma_histo.jpg

====Griscelli syndrome====
*Griscelli syndrome can result from a defective Rab27a protein which is part of the transport complex that moves '''melanosomes''' along '''microtubules'''

for cyotocrine passage to other cells.

==The eye==

===Optical anatomy===

http://www.odec.ca/projects/2006/thog6n2/images/eye_2.gif

===Wall of the eye===

https://lh6.googleusercontent.com/_WdFQawAlzZM/TaR2ollnmXI/AAAAAAAAAvc/Ql2QplUuCDY/s800/eyeball_layers.jpg

===Eyeball function by component===

http://www.cytochemistry.net/microanatomy/eye/retina4.jpg

====Cornea====
*The layers (superficial to deep): epidermis, Bowman's membrane, stroma, Descemet's membrane, and endothelium.
*'''With age, Descemet's membrane''' decreases in transparency and leads to '''decreased light transmission'''.

http://www.ophthobook.com/wp-content/uploads/2007/12/video-cornealayers.jpg

http://www.lasik.md/img/learnAboutLasik/cornea.gif

http://www.uniteforsight.org/course/image/cornea.jpg

http://thalamus.wustl.edu/course/eye2.gif

=====Epithelium of the cornea=====
*The epithelium of the cornea is made of '''stratified, squamous, non-keratinized epithelium'''.

http://www.dartmouth.edu/~rpsmith/lens.gif

http://www.bu.edu/histology/i/08006loa.jpg

http://library.thinkquest.org/28030/media/schlemm5.gif

http://1.bp.blogspot.com/_kaQ5P19FVgk/THl4ddhkNnI/AAAAAAAAG20/PtY3YVnIgpE/s400/Canal_de_Schlemm.JPG

=====Stroma of the cornea=====
*The stroma is series of layers of '''fibrocytes, proteoglycans, and ECM fibers''' with alternately oriented collagen fibers.
**Note that '''collagen of the stroma is of type 1 and 5''' and are '''non-fibrillar'''.

http://www.onset.unsw.edu.au/issue2/Contactlenses/Cornea.jpg

http://www.images.missionforvisionusa.org/anatomy/uploaded_images/KnumbMfV-735325.jpg

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Eye03_files/image002.jpg

=====Endothelium of the cornea=====

http://education.vetmed.vt.edu/Curriculum/VM8054/EYE/CRNEADGM.JPG

http://www.hopkinsmedicine.org/bin/n/r/layers_of_cornea.jpg

====Uvea====

http://www.uchospitals.edu/images/nci/CDR0000543553.jpg

=====Choroid of the uvea=====
*The choroid is '''highly pigmented''' and found between the sclera (part of the tunica fibrous) and the retina.
*The choroid has three layers: sclera vasculature, retinal vasculature, and Brunch's membrane.
**The retinal vasculature layer is also called the '''choriocapillary layer'''.
**Bruch's membrane is also sometimes called a ''glassy membrane''.

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSJaMYCunI/AAAAAAAAAvk/jp3rWecT1KU/s800/choroid.jpg

http://neuromedia.neurobio.ucla.edu/campbell/eyeandear/wp_images/175_choroid.gif

=====Ciliary body=====
*Far vision requires a flattened lens (think flat like a frisbee which you hope will go "far") so the ciliary muscle relaxes, the zonules tense, and the lens

is pulled into a flatter shape.
*Near vision requires a bulged lens so the ciliary muscle contracts, the zonules relax, and the lens relaxes into a bulge.
*'''Oxytalin''' fibers are used to attach the basement membrane of the non-pigmented epithelium of the ciliary body (part of the uvea) to the basement

membrane (called the lens capsule) of the lens.

http://www.unmc.edu/physiology/Mann/pix_7/ciliary.gif

*Ciliary processes:
***Aqueous solution has little protein, some glucose, and similar ion concentration as plasma.
***The pigmented layer (deep layer) of the ciliary process is continuous with the pigmented layer of the retina.
***The non-pigmented layer's (secretory, surface layer) apical surface faces the pigmented layer and the basolateral surface has lots of folds and borders

the posterior chamber.
**We call the space between the pigmented and non-pigmented cells the '''ciliary channel''' and consider it a ''potential space''.
**'''Blood-aqueous barrier''': '''occluding junctions''' at the apex of the ciliary process's surface epithelium keeps blood and aqueous solution from

mixing.

https://lh6.googleusercontent.com/_WdFQawAlzZM/TaSMDAw19oI/AAAAAAAAAv0/3JVlhulvX9I/s800/ciliary_body_diagram.jpg

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSJyetXfmI/AAAAAAAAAvs/-0q6gDNzx3M/s800/ciliary_body.jpg

http://www.kumc.edu/instruction/medicine/anatomy/histoweb/eye_ear/small/Eye006s.JPG

http://www.images.missionforvisionusa.org/anatomy/uploaded_images/lenszonulegrosscopy2-745514.jpg

http://www.unmc.edu/physiology/Mann/pix_7/ciliary.gif

http://a248.e.akamai.net/7/248/430/20080327144040/www.mercksource.com/ppdocs/us/common/dorlands/dorland/images/zonula_z.%20ciliaris(1).jpg

=====Iris=====
**Note that the posterior epithelium is one and the same as the myoepithelium: it has muscle fibers in it and is responsible for '''dilating''' the pupil.

*'''The malanocytes of the stroma determine eye color.'''
*The stroma is responsible for '''constricting''' the pupil.

*Note that '''dilation is sympathetic''' and '''contraction is parasympathetic'''.

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSpFlJEapI/AAAAAAAAAwI/SRnGaDvroPU/s800/pigmented_myoepithelium.jpg

=====Eye color=====
**http://farm4.static.flickr.com/3093/3196152077_f205a4c2f2.jpg

====Lens====
*The epithelium on the anterior side of the lens is '''simple cuboidal'''.
*Note that '''the lens epithelium does not have occluding junctions'''.

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSrrG6wx6I/AAAAAAAAAwM/KRh5L-hAn_k/s800/lens_cells.png

*In the case of cataracts, lens fibers (the cells that span ant-post and have crystallin) turn opaque and refract light poorly.
*In the case of '''presbyopia''', the lens loses elasticity (some loss is normal during aging) such that the pt cannot ''accomadate'' well and thus has

'''poor near vision'''.

====Retina====

=====Pigmented epithelium of the Retina=====
*The pigmented epithelium of the retina is '''simple cuboidal''' and is adjacent to the inner-most layer of the uvea (Bruch's membrane).
**Note that secretion is enabled via '''Na-K ATPase'''.
**concentrates ''and estrifies'' vitamin A for easy reproduction of rhodopsin by rods

=====Neural retina=====

http://upload.wikimedia.org/wikipedia/en/b/bb/Rod%26Cone.jpg

http://www.medgadget.com/archives/img/retinal_layers.jpg

*Rods versus cones
**Rods use rhodopsin while cones have three distinct pigments for three colors: red, green, and blue.

{|border="1"
|-
!Attribute
!Rods
!Cones
|-
|Function
|Night vision (scotopic), low acquity
|Day vision (photopic), color, high acquity
|-
|Photopigment
|Rhodopsin
|3 pigments, 3 wavelength specificities
|-
|Distribution
|"Peripheral"
|"Central"
|-
|Population count
|120 million
|6 million
|}

https://lh4.googleusercontent.com/_WdFQawAlzZM/TaSy4rD93wI/AAAAAAAAAwQ/bgroeQF5CBY/s800/retina.png

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSJyetXfmI/AAAAAAAAAvs/-0q6gDNzx3M/s800/ciliary_body.jpg

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSzKsKAgYI/AAAAAAAAAwY/n4kWukRfoD8/s800/fovea.jpg

Exam 3 review

149.166.24.214 — Wed, 13 Apr 2011 19:22:54 GMT

149.166.24.214: Created page with '*Exam 3: **A-M: lab first, MS 109-116, 9am-10:20am **M-Z: lab second, MS 326, 10:30-11:50 *NBME **04/22/11 **Arrive early'

*Exam 3:
**A-M: lab first, MS 109-116, 9am-10:20am
**M-Z: lab second, MS 326, 10:30-11:50

*NBME
**04/22/11
**Arrive early

P's exam 3 study guide

134.68.138.227 — Wed, 13 Apr 2011 15:35:34 GMT

66.194.104.5:

==Urinary 1==
http://image.wistatutor.com/content/excretion/malpighian-nephron-structure.jpeg

===Cortex and Medulla===
*Urine is produced by '''lobes''' which contain a single '''renal papillum''' which dumps urine into the '''pelvis''' which dumps into the ureter.

http://www.sweethaven02.com/MedTech/AnatPhys/human01_37.jpg

http://iws.collin.edu/mweis/Images/Dissections/pig%20dissections/pig%20dissections%20labeled/pig_kidney_cortex_medulla_calyces_labeled.png

===More on macrostructure===
*Medullary pyramids are separated by '''renal columns of Bertin'''.

http://www.sci.sdsu.edu/classes/bio100/Lectures/Lect16/Image271.gif

===Uniferous tubule function===
http://www.siumed.edu/~dking2/crr/images/RN003b.jpg

===Uriniferous tubule layout and embryonic development===
*The first form of a plasma filtering mechanism in the developing human embryo is called the '''mesonephric kidneys'''.
*Mesonephric kidneys reach their maximum size at 8 weeks and then undergo a large change ''and eventually are not kidney-like at all''.
*Parts of the mesonephric kidneys persist in men to form:
**the efferent ductules,
**the epididymis,
**the ductus deferens, and
**the ejaculatory duct.
**so, everything ''after'' the straight tubules.

*'''The metanephros gives rise to the permanent kidneys.'''
**The metanephros contains the '''metanephric mesenchyme''' and the '''uritic bud'''.
**The uritic bud and the metanephric mesenchyme are both composed of epithelial cells.
*The uritic bud grows up into the '''nephrogenic mesoderm''' which is part of the metanephros.

===Uritic bud and nephrogenic mesoderm interaction===
*The uritic bud grows into the nephrogenic mesoderm to form the mature uriniferous tubules.
*The interaction between the uritic bud and the nephrogenic mesoderm is called '''reciprocal induction'''.

*As the uritic bud grows into the nephrogenic mesenchyme, the '''uritic bud''' is the primary epithelial cell tubule structure that will become the collecting duct.
**Recall that mesenchymal cells are connective tissue cells.
**Recall that mesenchyme looks like loose connective tissue with lots of spindly, undifferentiated cells within.
*Renal corpuscles develop along the length of the uritic bud (that is, the developing collecting duct) and therefore can originate from the tip of the uritic bud or from epithelium that develops along side the uritic bud.

*Renal corpuscle and nephron development from the tip of the uritic bud:
**At the tops of the uritic bud, mesenchymal cells of the nephrogenic mesenchyme '''condense''' and are induced to make a '''mesenchymal-epithelial transition''' (MET).
***Condensation includes proliferation
**These MET cells will become the epithelial cells of the glomerular capsule.
**The bud tip then expands to develop the PCT (proximal convoluted tuble), loop of Henle (LoH), and the DCT (distal convoluted tubule).
**The MET shifted cells of the early glomeruli recruit the formation of blood vessels that will become the glomerular capillaries.

*Renal corpuscle and nephron development adjacent to the uritic bud:
**Along side the uritic bud, epithelial tracts form as '''S-shaped''' or '''comma-shaped''' tubule structures.
**The tops of these se epithelial tracts will become the glomeruli and the length will become the PCT, LoH, and the DCT.

*The s-shaped buds from condensation, proliferation, and MET of mesenchymal cells will form the PCT, LoH, and DCT.

http://herkules.oulu.fi/isbn9514269918/html/graphic11.jpg

http://img.medscape.com/fullsize/migrated/editorial/journalcme/2008/12499/kerecuk.fig1.gif

http://www.sonoworld.com/images/FetusItemImages/article-images/urinary_and_adrenal/prune_belly_syndromes_files/image78.jpg

===Renal corpuscle structure===
*Note that '''podocytes are a type of epithelial cell'''.
*Capillaries are a type of endothelial cell.
*Within the capillaries as they develop within the glomerular tuft, there is '''connective tissue holding the capillaries in place'''.
**This connective tissue is called '''mesangium'''.

*The visceral bowmans capsule is made up of podocytes.
*Often there is pink material in the bowmans space; it is brush border from the proximal tubule that has washed backward during fixation.
*The distal convoluted tubule (which is, like the PCT, made up of epithelial cells) passes by the afferent arteriole along side the glomerulus.
**The DCT has specialized cells called '''macula densa cells'' on the surface that is closest to the afferent arteriole.
**Macula densa cells release signals PGE2 to cause the afferent arteriole to vasodilate and ATP to cause the afferent arteriole to constrict.
**Macula densa cells are more columnar, stain darker, and have rounder nuclei than the endothelail cells of the DCT.

*Juxtaglomerular cells (also called granular cells) are endothelial cells of the afferent arteriole that contain '''granules of renin'''.
**Granular cells (AKA juxtaglomerular cells) have a large, flattened nucleus, that is more prominent than the nucleus of lacis (extraglomerular mesangial) cells.
**Granular cells release their renin upon PGE2 binding their EP4 receptor.
**Recall that renin will activate angiotensinogen leading to angiotensin 2 and systemic vasodilation.

*Lacis cells (also called extraglomerular mesangial cells) hold the DCT, the afferent arteriole, and the glomerulus together.
**Extraglomerular mesangial cells may also have some functioning in modifying the signals released by the macula densa cells as they travel to the granular / endothelial cells of the afferent arteriole.
**Lacis cells (extraglomerular mesangial cells) are found between the macula densa cells and the afferent arteriole endothelial cells.
**Lacis cells have a lighter stain and less prominent nucleus as compared to granular (juxtaglomerular) cells.
**Extraglomerular mesangial cells are found between the convoluted capillaries, too, and serve to hold the loops in their structure.
***In this case, the mesangial cells are located within the basement membrane.
**Lacis cells can send processes into the lumen of the capillaries between the endothelial cells.

http://sitemaker.umich.edu/ransom.lab/files/glomerulus.jpg

http://www.nature.com/ki/journal/v74/n1/images/ki2008128f4.jpg

http://cmm.ucsd.edu/farquhar/images/Res6_Fig2_EM_Podocyte.gif

http://homepage.smc.edu/wissmann_paul/physnet/anatomynet/anatomy/podocytes2.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab23/IMAGES/VASPOLE2%20B.jpg

http://www.kidneypathology.com/Imagenes/Histologia/Histo_AYG_2.jpg

===Forming a filter at the capillary-Bowman-space junction===
*The filtrate must first get through the endothelium of the capillary, then through the basement membrane, and then through the feet of podocytes.

*The endothelium of glomerular capillaries is '''fenestrated without diaphragms''' to allow only very small proteins and smaller molecules through.

*The basal lamina restricts even the smallest proteins.
**There are three layers to the basal lamina (basement membrane) of the glomerulus.
**The three layers are probably only separate in slides as a result of processing, but they are still effective markers for pathology.
**The '''lamina rara extrna''' is farthest from the lumen of the capillary.
**The '''lamina rara interna''' is closest to the lumen of the capillary.
**The '''lamina densa''' is between the ''lamina externa'' and the ''lamina interna''.
**These layers appear as a light-dark-light pattern in EM.

*Podocytes are a type of epithelial cell that provide the finest level of filtration ('''slit pore diaphragms''') of the plasma as it crosses into the Bowman space.

*Water and small molecules pass freely into the Bowman space.
*It is still disputed what factors play the primary role in keeping proteins from entering the filtrate.
**Some say the anionic charge of the basement membrane, which would repel proteins which are generally negatively charged, is the primary factor that hinders protein passage.
**Others point to the podocyte processes and the important proteins that make up the processes (ZO1, nephrin, Neph1) as the primary protein-hindering mechanism.
**Nephrin seems to form a lattice between podocyte processes that would prevent proteins from passing into the bowman space.
http://www.nature.com/ki/journal/v73/n6/images/5002798f1.jpg
**Recall that '''ZO1 is associated with tight junctions'''.

===Mesangial cells===
*Recall that mesangial cells reside between capillaries within the basement membrane.
**Recall that '''basement membranes are always made of type 4 collagen!'''
*Mesangial cells may modulate capillary blood flow.
*Mesangial cells may also act as phagocytes within the basement membrane of the glomerulus.
*Mesangial cells '''reaches out and cups''' each capillary around it.
*Mesangial matrix is made up of collagen, glycans, proteoglycans, etc.

http://www.siumed.edu/~dking2/crr/images/corp5.jpg

http://herkules.oulu.fi/isbn9514264290/html/graphic55.png

http://content.answcdn.com/main/content/img/oxford/Oxford_Body/019852403x.cell.1.jpg

http://www.ndt-educational.org/images/MGP0001.jpg

===The proximal tubule===
*The proximal tubule is characterized by being large, being eosinophilic (cuboidal, continuous, uniform), and having central nuclei.
*The proximal tubule demonstrates '''cells with brush border and basolateral membrane folding in order to increase its surface area'''.
**Note that during fixation, the brush border often sloughs off into the lumen.
**The proximal straight tubule '''continues through the outer stripe''' of the outer medulla.
**"Straight segments ... terminate at a remarkably uniform level ... that establishes the boundary between the inner and outer stripes of the outer ... medulla." per [http://en.wikipedia.org/wiki/Proximal_convoluted_tubule wikipedia]
**Note that this is true for both cortical- and juxtamedullar glomeruli-derived proximal straight tubules.

===Cell distinction along the PCT, LoH, and DCT===
*Recall that the cells of the PCT, LoH, and DCT are all epithelial cells specialized for reabsorption and / or secretion.
*There are four regions that can be distinguished by cell morphology and characteristic: PCT / thick descending limb, thin descending / thin ascending, thick ascending / DCT, and the collecting duct.
*Note that the thick descending tubule is the same as the proximal straight tubule; the same goes for the distal region: distal straight tubule = thick ascending tubule.

====Cells of the PCT and PST====
*Note that the '''PST = proximal straight tubule = thick descending / proximal loop'''.
*There are only epithelial cells in the PCT and thick descending loop.
*Epithelium of the PCT is a simple squamous epithelium.
*'''the cells of the PCT and thick descending tubule are the only cells with a brush border'''.
*Cells of the PCT and thick descending tubule also have nuclei that are spaced far apart.
*PCT / thick descending tubule epithelial cells stain very pink.

====Cells of the thin descending and thin ascending tubules====
*There are only epithelial cells in the thin descending and ascending tubules.
*Recall that '''the descending loop is passively, highly permeable to water and solutes.'''
*Recall that '''the ascending loop is impermeable to water and actively secretes Na and Cl.'''
*The epithelial cells of the thin regions are thin cells that stain lightly.
*The nucleus of epithelial cells of the thin tubules is smaller than other nuclei of tubular epithelial cells.

====Cells of the DST and DCT tubules====
*The epithelium of the DCT and thick ascending tubule is '''thicker than the PCT and thick descending tubule'''.
*cell types in the thick ascending and DCT tubules: epithelial cells, macula densa cells, and ''principal cells'', intercalated cells.
*Epithelial cells of the thick ascending tubule and DCT need lots of protein to facilitate ion transport and so it makes sense that '''thick ascending epithelium and DCT epithelium have lots of mitochondria'''.
*Epithelial cells of the thick ascending tubule and DCT have '''apical nuclei that bulge outward''' (perhaps because of the mt that are pushing them apically).
**'''Macula densa cells appear at the last part of the thick ascending tubule'''.
*The DCT is the first site of '''intercalated cells'''.

=====Differentiating PST and DST=====
*Thick descending epithelium stain darker than thick ascending epithelium.
*Thick descending epithelium has more basally located nuclei while ascending epithelium have apically located nulcei.
*Thick descending has a thicker wall than the thick ascending.

=====PCT versus PST and DCT versus DST identification=====
*Note that PST and PCT can be differentiated because they are never found in the same location: PCT is in the convoluted area and PST is only in the medullary ray area.
*Because the DCT and DST are both bound in the cortex, it is likely impossible to tell them apart (unless the structure in question runs right up next to a glomeruli and has macula densa at which point we know it is a DST).

http://www.ouhsc.edu/histology/Glass%20slides/35_10.jpg

http://www.medicalhistology.us/twiki/pub/Main/ChapterSeventeenSlides/b68_proximal_convoluted_tubule_kidney_40x_pas_labeled.jpg

=====Differentiationg PCT and DCT=====
*PCT and DCT can be distinguished by their stain and size:
*PCT epithelium has a brush border but DCT epithelium does not, though often the brush border is not preserved.
*PCT stains darker than DCT, though sometimes it can be the opposite, so good luck with that.
*PCT is made of larger cells than DCT (so with PCT you travel farther around the tubule before finding the next nucleus).

http://www.lab.anhb.uwa.edu.au/mb140/corepages/urinary/images/kidneydiagram.jpg

====Cells of the collecting duct====
*Epithelial cells of the collecting duct bulge into the lumen.
*Epithelial cells of the collecting duct have clear distinctions between each cell and have nuclei that ''do not bulge'' (like PCT / thick ascending tubule epithelial cells).
*Nuclei are more basal and irregularly shaped.
*Principal cells are hormonally controlled for water reabsorption and are the '''major site of potassium regulation'''.
**Principal cells absorb Na and secrete K.
**Principal cells are generally impermeable to water but can become water absorptive when ADH is present (think AQ2).
*Intercalated cells '''stain darkly''', bulge a little into the lumen, have no brush border, have a more apical nucleus than principal cells, and are the site of pH regulation.

*There are '''three sections to the collecting duct''': the connecting tubule and cortical collecting tubule, the outer medullary collecting tubule, and the inner collecting tubule.
**The two proximal sections (connecting duct / cortical collecting duct and the outer medullary collecting duct) have principal '''and''' interstitial cells; the inner medullary collecting duct has '''only principal cells'''.
**The inner medullary collecting duct is also called the '''papillary collecting duct'''.
**The last section of the inner medullary collecting duct is called the '''duct of Bellini'''.

===Distinguishing regions of the kidney===
*Note that thin segments of the LoH and DCT / PCT never occur in the same area so they can be used to determine the origin of a section.
**'''Thin loops of Henle are only found in the medulla.'''
***Recall that the thick proximal tubule terminates at the outer-inner stripe border of the medulla.
**'''Convoluted tubules are only found in the medulla.'''
*Distinguishing the medulla:
**The inner medulla has only asc / desc thin tubules and the collecting duct.
**The inner stripe of the outer medulla has asc / desc thin tubules, proximal / distal thick tubules, and the collecting duct.
**The outer stripe of the outer medulla has only thick tubules and collecting duct.
*'''There are no glomeruli in the medulla!'''

==Urinary 2==

===Loop of Henle===
*When the NaCl level is high, we want slow the filtrate flow rate so we have time to reabsorb all that valuable NaCl; therefore, when the NaCl level in the filtrate is high macula densa cells release ATP to constrict the afferent arteriole and decrease GFR.
*Conversely, very little NaCl in the filtrate at the macula densa means that the filtrate has had lots of time to have its NaCl reabsorbed so we can speed up GFR. In this case, macula densa cells release prostaglandins that cause renin release (and subsequently vasodilation) at the afferent arteriole.

===More kidney superstructure===
http://www.comprehensive-kidney-facts.com/images/KidneyAnatomy.jpg

*Note that '''the ascending thick tubule is deeper than the descending thick tubule'''.
*'''Arcuate vessels''' follow the boundary of the cortex and medulla, giving off '''interlobular vessels''' that give off '''afferent arterioles''' and receive '''stellate vessels'''.

*The thick descending tubule = proximal straight tubule = pars recta.

*We can remove kidney stones through a surgery that pierces the cortex, enters a calyx, and uses a probe to grab / destroy the stone. '''Percutaneous nephroscopy'''.

===Renal vasculature===
*The order of renal blood flow: renal artery -> inter''lobar'' artery -> arcuate artery -> cortical radial artery (imagine these radiating outward from the arc; used to be called interlo''bu''lar arteries) -> afferent arteriole -> glomerular capillaries -> efferent arteriole.
*The return route can start from two locations:
**Superficial and mid-cortical glomerulus: (from efferent arteriole) peritubular capillaries
***superficial peritubular capillaries return via stellate veins -> arcuate vein...
***deeper peritubular capillaries return via cortical radial vein -> arcuate vein...
**Juxtamedullary glomerulus: (from efferent arteriole) descending vasa recta -> ascending vasa recta -> arcuate vein...
*Then both follow the same path away from their respective nephron: arcuate vein -> inter''lobar'' vein -> renal vein.

http://biomed.brown.edu/Courses/BI108/BI108_2001_Groups/WAK/renalphys/images/image3.jpg

===Cortex organization===
*A '''renal lobule''' is a unit of renal tissue with medullary ray at the center with cortical radial vessels bounding it on the outsides.
**So '''medullary rays are the ascending and descending tubules that will run perpendicular to the capsule of the kidney.'''
**So, '''a cortical labyrinth is a collection of renal corpuscles with their associated medullary rays'''.

===Juxtuloglomerular apparatus and the renin-angiotensin pathway===
*Renin is released by granular cells (juxtaglomerrular cells).
**Angiotensin 2 causes systemic vasodilation.
*The apparatus contains the afferent and efferent arterioles, the macula densa, and the extraglomerular cells (lacis cells).
**There are also juxtaglomerular cells which are '''smooth muscle / endocrine cells.'''

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/F16-5.jpg

http://allaboutim.webs.com/JGA%20-%203D.jpg

http://www.medicalhistology.us/twiki/pub/Main/ChapterSeventeenSlides/b67_macula_densa_renal_corpuscle_40x_he_labeled.jpg

===Post-kidney urinary ultrastructure===
*The calyces, pelvis, ureters, bladder, and uretra all have the same histological structure.
**The only exception is that the walls of the ureters become thicker as they continue.
*The calyces through bladder are '''transitional epithelium''' with a '''lamina propria''' and '''smooth muscle'''.
**Transitional epithelium allows these structures to change volume easily, which is most obviously important in the bladder.
**The lamina propria holds the cells together with connective tissue when changing volume.
**The smooth muscle allows contraction for movement of urine along the tract.

===Transitional epithelium of the bladder===
*Uroplakins can fold up like a pleat.
*A protein called '''uroplakin''' can be moved to the surface or removed from the surface via vesicular movement in order to increase or decrease surface area.
**Vesicles that contain uroplakin are called '''fusiform cytoplasmic vescicles'''.
*Uroplakin, as with all membrane proteins, is generated via the rER and golgi apparatus.
*Where uroplakin is on the surface, the membrane is thicker; there are thinner areas of membrane that are distict in EM of bladder epithelium.

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/bladder4.jpg

http://www.orienttumor.com/zh_asp_new/zt/ENGLISH/t&t/Bladder_Cancer/001_s.jpg

http://neuromedia.neurobio.ucla.edu/campbell/urinary/wp_images/49_transitional_epithelium.gif

===Smooth muscle of the bladder===
*Smooth muscle of the calyces, pelvis, and ureters are '''helical''' in pattern.
*Smooth muscle in the bladder is '''longitudinal''' and runs in all directions.

==Endocrine histology==

===Describe the structural organization of the endocrine system===
*Note that exocrine glands secrete onto an epithelial surface that is usually in the form of a duct whereas endocrine glands secrete into the blood stream.
**Furthermore, both exocrine glands and endocrine glands are usually on the '''outside of the basement membrane''' relative to the blood.
**Therefore, exocrine glands do not secrete across the basement membrane.
**However, '''endocrine glands often must secrete their hormones across the basement membrane'''.

===Define components of the endocrine system===

===Describe the embryonic origin, histological organization, and hormone secretion of the endocrine system===

====Origin, organization, and secretion of the hypothalamus====
*The hypothalamus releases 5 hormones from three nuclei (dorsal medial, ventral medial, and infundibular nuclei):
**TRH which stimulates thyrotropes and mammotropes (lactotropes) of the anterior pituitary to release TSH and PRL.
**PIF (prolactin inhibitory factor, dopamine) which inhibits lactotropes ('''mammotropic cells''') of the anterior pituitary from releasing PRL.
**SST (somatostatin) which '''inhibits''' somatotropes and thyrotopes of the anterior pituitary (adenohypophysis) to release GH and TSH.

*The hypothalamus also contains two more nuclei that produce two other hormones that are delivered directly to the posterior pituitary (neurohypophysis) through the axons of the neuron cells that produce the hormones.
**The '''supraoptic neucleus''' produces vasopressin (ADH, AVP) which acts on the collecting ducts of the kidney (think AQ2).
**The '''paraventricular nucleus''' produces oxytocin which acts on the mammary glands (myoepithelial cells) and uterus (smooth muscle cells, contractions).

====Origin, organization, and secretion of the pituitary gland (hypophysis)====
*The anterior pituitary consists of the pars distalis, the pars intermedia, and the pars tuberalis.
*The posterior pituitary (neurohypophysis) is made up of the pars nervosa and the median eminence.

http://academic.kellogg.edu/herbrandsonc/bio201_mckinley/f20-4_pituitary_gland_c.jpg

http://www.ouhsc.edu/histology/Glass%20slides/38_11.jpg

*The neuroectoderm (floor of the diencephalon) grows caudally, forms a stalk, and remains attached to the brain tissue of origin.
http://www.cytochemistry.net/endocrine_system/pitdraw2.jpg

=====Adenohypophysis (anterior pituitary)=====
*The pars distalis (anterior lobe):
**The pars distalis is composed of '''fibroblast generated reticular fibers''' that support hormone-generating epithelial cells and a rich bed of '''fenestrated capillaries'''.
**Cells of the pars distalis can be classified by the way the stain: basophilic, acidophilic, and chromophobes.
**Acidophilic cells: somatotropes and mammotropes (lactotropes).
**Basophilic cells: gonadotropes, croticotropes, and thyrotropes
**Chromophobic cells: stem cells, degranulated cells that would otherwise be chromophilic (see acidophilic and basophilic).
**'''Differentiating cell types is not possible with light microscope''', only by trasmission electron microscopy can these hormone producing cells be differentiated.
http://embryology.med.unsw.edu.au/histology/endocrine/hya40he.jpg

*The pars tuberalis:
**Most cells of the pars tuberalis are '''basophilic'''.

*The pars intermeida:
**Colloid-filled cysts fill the pars intermedia.

=====Neurohypophysis (posterior pituitary)=====
*The neurohypophysis contains '''nerve cells and glial cells (pituicytes)'''.

*The pars nervosa:
**The pars nervosa contains fibroblasts, pituicytes, mast cells and neurons.
**The neurons arise from the paraventricular and supraoptic neuclei where oxytocin and vasopressin are made, respectively.
**These neurons are atypical in that they do not synapse at their distal axons.
**The '''hormones released by these neurons are stored in granules (called Herring bodies or neurosecretory bodies''') at the distal aspect of the axon.
***Herring bodies can be identified under light microscopy.

*The infundibular stalk
**The infundibular stalk, like the pars nervosa, contains atypical nerve axon endings that release hormones.
**The neurons of the infundibular stalk release their hormones into the hypothalamus-pituitary portal system and affect the cells of the anterior pituitary.

=====Pituitary portal system=====
*There are really 4 main components to the portal system: primary and secondary capillary beds, long veins and short veins.
*The primary capillary bed arises from the superior hypophyseal artery and resides around the median eminance.
*The long veins connect the primary capillary bed to the secondary capillary bed.
*The secondary capillary bed resides around the adenohypophysis.
*The inferior hypophyseal artery forms a capillary mesh at the neurohypophysis.
*The short veins connect the capillaries of the neurohypophysis to the secondary capillary bed of the adenohypophysis.

====Origin, organization, and secretion of the Adrenal glands====
*The outer shell is made of dense connective tissue that sends '''septa into the center of the organ as trabechulae'''.
**Cortex from mesoderm, medulla from neuro ectoderm.

http://www.histology-world.com/photomicrographs/adrenallabel.jpg

=====Adrenal cortex=====
*GomiFacoRea: glomerulus-mineralocorticoids, fasciculata-corticoids, reticularis-androgens.

http://ouhsc.edu/histology/Glass%20slides/39_11.jpg
http://ouhsc.edu/histology/Glass%20slides/39_03.jpg

*The glomerulosa:
**The glomerulosa layer is characterized by '''closely-packed, arched chords of columnar or pyramidal cells''' surrounded by '''capillaries'''.
**The glomerulus can be differentiated from the capsule because of increased cellularity, prominent, circular nuclei, prominent arches, less connective tissue (which usually stains bright pink).

*The fasciculata:
**The fasciculata is characterized by '''long chords of polyhedral cellls''' and '''fenestrated capillaries'''.
**The fasciculata can be differentiated from the glomerulosa by distinct change in from short, bulbous cellular collections to long chord-like cellular collections.

*The reticularis:
**The reticularis can be differentiated from the fasciculata by less organized cellular collections, more eosinophilic staining (pinker, think about the granules of norepi and epi),

http://www.vet.uga.edu/vpp/clerk/groover/Fig1.jpg

http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_%26_Physiology/A%26P202/Endocrine_System/histology_jpgs/adrenal_40x_P2252261lbd.JPG

http://wikis.lib.ncsu.edu/images/7/7a/Adrenalcortex.JPG

http://www.udel.edu/biology/Wags/histopage/colorpage/cen/cenzgf.GIF

http://withfriendship.com/images/i/43179/adrenal-medulla-hormones.jpg

=====Adrenal medulla=====
*The medulla of the adrenal is composed of '''chromaffin cells''' which can be considered like post-ganglionic neurons.
*Chromaffin cells can either be '''norepinephrine producing or epinephrine producing''' and will have '''granules full of their labors'''.
**Norepinephrine-producing Chromaffin cells are found near medullary arteries.
**Epinephrine-producing Chromaffin are found near cortical sinuses.
*Cell density within the medulla is less than that of the cortex.

http://wikis.lib.ncsu.edu/images/5/50/Adrenalmedu.jpg

http://www.deltagen.com/target/histologyatlas/atlas_files/endocrine/adrenal_gland_medulla_40x.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab24/IMAGES/ADMEDULL.jpg

http://histology-world.com/photoalbum/albums/uploads/normal_medulla40X_lbl.jpg

====Origin, organization, and secretion of the Pancreas====
*The endocrine portion of the pancreas arises '''from endodermal tissue near the bile duct'''.
**The notes also say that the endocrine protion arises '''from epithelium of the gut'''.
*There are four cell types in the endocrine islets of langerhans: beta, alpha, delta, and F / pp cells (by abundance).
*Delta cells make somatostatin.

http://www.daviddarling.info/images/islets_of_Langerhans.gif

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/islets.jpg

http://www.medicalhistology.us/twiki/pub/Main/ChapterThirteenSlides/b36_interlobular_duct_pancreas_10x_labeled.jpg

http://www.ric.edu/faculty/ptiskus/Stem_Cells/Image3.gif

====Origin, organization, and secretion of the Thyroid====
*'''Within or between''' the follicles can be found '''C cells (parafollicular cells)''' which produce '''calcitonin'''.

*Production, storage, and release of thyroid hormones '''involves both endocrine and exocrine functions'''.
*Thyroglobulin made in rER, glycocylated in rER / golgi, and moved into the lumen.

http://img.tfd.com/vet/thumbs/gr387.jpg

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/thyroid4F.jpg

http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_&_Physiology/A&P202/Endocrine_System/histology_jpgs/thyroid_400x_P2252255lbd.JPG

http://ouhsc.edu/histology/Glass%20slides/42_04.jpg

http://www.drharper.ca/images/HPT%20Axis.gif

====Origin, organization, and secretion of the Parathyroid glands====
*The Parathyroid gland '''arises from the pharyngeal pouches'''.
*Like the adrenal glands, the parathyroid glands have a '''capsule with septa that run inward'''.
*The parathyroid gland is composed of two cell populations: chief cells and oxyphil cells.

*Chief cells:
**Chief cells '''contain eosinophilic granules of PTH'''.
**Note that regulation of chief cell PTH release is an '''inhibition of inhibitoin mechanism: when serum Ca levels decrease, fewer Ca-receptors bind Ca (the ligand) causing a decrease in intracellular signaling and an increase of PTH release'''.

*Oxyphil cells:
**The function of oxyphil cells is unknown; however, it is known that they arise during puberty.
**Oxyphil cells are '''larger than chief cells''' with an acidophilic cytoplasm and '''abnormally shaped mt'''.
**Oxyphil cells are often found in clusters at the center of the parathyroid gland or near the perimeter.
http://www.ouhsc.edu/histology/Glass%20slides/40_06.jpg

http://www.bu.edu/histology/i/15002loa.jpg

http://neuromedia.neurobio.ucla.edu/campbell/endocrines/wp_images%5C137_cells.gif

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/Image514.gif

=====Primary hyperparathyroidism=====
*Primary hyperparathyroidism is a defect with the parathyroid itself causing an '''an elevation of PTH'''.
*Giving PTH intermittently to post-menopausal women is associated with decreased risk of bone fracture.
**'''continuous administration of PTH causes bone loss yet intermittent PTH administration causes increases in bone mass'''.

====Origin, organization, and secretion of the Pineal gland====
*The pineal gland arises from '''neuroectoderm from the floor of the diencephalon''' (just like the neurohypophysis).
*The pineal gland is pine-cone shaped and covered with connective tissue.
**This pine-cone shaped pineal gland is located in the '''posterior aspect of the third ventricle'''.
http://www.rickrichards.com/chakras/pituitary_brain2a.jpg
*The pineal gland contains pinealocytes, interstitial glial cells (like astrocytes).
*The pinealocytes produce '''melatonin''' and thus take part in daily rhythmicity.
*'''Rene Descarts''' explained human behavior and thought via the pineal gland because of its involvement in sensation, imagination, memory, and bodily movement.

http://ouhsc.edu/histology/Glass%20slides/41_02.jpg

http://embryology.med.unsw.edu.au/histology/endocrine/pin42he.jpg

====Origin, organization, and secretion of the Diffuse Neuro-endocrine system====
*Organs that have diffuse endocrine tissue include the '''heart, kidney, thymus, gut, and gonads'''.

=====Bone as an endcrine organ=====
*Two major signals are released by bone to affect physiology: FGF23 and uOCN.

*FGF23 is released by the bone and causes:
**Kidneys decrease phosphate (Pi) reabsorption resulting in decreased serium Pi.
**Kidneys decrease 1,25VitD activation resulting in decreased serum 1,25OH VitD and decreased Ca reabsorption.
**So FGF23 is generally an anti-bone-building signal.

*uOCN is released by the bone and causes:
**Pancreatic beta cells to increase insulin release resulting in decreased serum glucose.
**Adipocytes to increase adiponectin resulting in changes to glucose and fatty acid catabolism.
**Muscle to increase sensitivity to and uptake of glucose resulting in decreased serum glucose.
**So uOCN is generally a pro-growth-use-up-the-glucose signal.

*Bone also releases '''osteocalcin''' which has been shown to be associated with poor fertility when deficient.

==Female reproductive histology==

===Ovarian cycle===

====Origin and fate of ovarian follicles====
*Ovarian follicles are composed of a germ cell (oocyte) surrounded by supporting cells (follicular epithelial cells).
*Primordial germ cells originate from the yolk-sac (endoderm) and migrate to the genital ridge where the ovaries are developing.

====Ovarian anatomy====
*The cortex epithelium of the ovary is simple cuboidal epithelium.

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/A%20ovary.jpg

http://www.ouhsc.edu/histology/Glass%20slides/83_02.jpg

====Ovarian follicle====
*During the ovarian follicular phase '''mesenchymal cells will differentiate into theca cells''' to surround the follicle with an extra two layers.
**The endocrine layer of theca cells is called the '''theca interna'''; the vascular layer of theca cells is called the '''theca externa'''.
*The ovarian follicle has a specific anatomy of layers:
***Within the follicular cell population one may find a '''Call-Exner body''' which are collections of granulosa cell membrane with granulosa secretions within.
**The follicular cells are surrounded by a '''basement membrane (basal lamina)'''.
**The basal lamina is surrounded by theca cells (from mesenchyme) which form two layers: theca interna and theca externa.

http://www.ft-patho.net/index.php?plugin=ref&page=Follicle&src=callexner.jpg

http://www.deltagen.com/target/histologyatlas/atlas_files/female_rep/ovary_10x.jpg

http://www.deltagen.com/target/histologyatlas/atlas_files/female_rep/ovary_40x.jpg

http://biology.nicerweb.com/Locked/media/med/Test/mitosis/cat_ovary.jpg

====Stages of the ovarian follicle====
http://farm4.static.flickr.com/3642/3475790550_9bf0d2c33f.jpg

http://i27.photobucket.com/albums/c190/lovesthesunset/anatomy%20and%20physiology/ovaryfollicles.jpg

*Developing follicle:
*In the developing follicle, '''the follicular cells are cuboidal''' and have proliferated and differentiated into '''granulosa cells'''.

*Secondary follicle:
*The secondary (vesicular, antral) follicle is '''uniquely defined by a developing antrum and a theca externa'''.
*Granulosa cells '''secrete stroma-weakening factors''' to allow expansion of the follicle.
**A primary stroma-weakening factor is '''plasminogen-activator''' which converts plasminogen to '''plasmin (fibrinolysin, a trypsin-like enzyme)''' which cuts up fibrin.
*Granulosa cells '''secrete a meiosis-regulationg factors''' to inhibit movement from prophase 1 to metaphase 2 in the oocyte.
*It is in the secondary follicle stage (antral stage, vesicular stage) that the '''oocyte reaches its mature size.'''

http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/secondary.jpg

*Mature follicle:
**The corona radiata is sometimes called the '''rim'''.
**The cumulus oophorus is sometimes called the '''stalk'''.
*Mature follicles are very large: can be over 1 cm!
*As a mature follicle, the oocyte '''progresses from prophase of meiosis 1 to metaphase of meiosis 2''' and thus generates the '''first polar body'''.
**Note that having entered meiosis 2, the oocyte is called a '''secondary oocyte'''.


http://t0.gstatic.com/images?q=tbn:ANd9GcR_5ajvKIDofXIvPSq_8CEqUgDbjlsBRtYNqKEDaGYemdfQoqPAtQ

http://www2.sunysuffolk.edu/sabatil/ovary400xl.gif

*Deciding on which type of follicle you're observing:
**flattened follicular cells: primordial
**cuboidal folliclar cells (with a layer on either side--zona pellucida or basal lamina): developing
**antrum / fluid: secondary follicle
**no way to distinguish secondary from mature.

http://ocw.tufts.edu/data/4/221179/221181_xlarge.jpg

http://classroom.sdmesa.edu/anatomy/Histologyphotos/Reproductive/Ovary%202.jpg

*Here is a good image (though it does not show a mature follicle):

http://academic.kellogg.edu/herbrandsonc/bio201_mckinley/f28-4a-d_ovary_c.jpg

http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_&_Physiology/A&P203/Reproductive_Tract_Histology/developing_follicle_400x_lbld_P5230104.jpg

http://www.histol.chuvashia.com/images/female/ovary-04-l.jpg

====Endocrine regulation of follicle maturation====
*'''Increased estrogen inhibits FSH release at the pituitary''' thus stopping the growth of the follicle and allowing ovulation.
*'''Increased estrogen stimulates LH release at the pituitary''' thus commencing ovulation.

*Recall these classic images:
http://faculty.stcc.edu/AandP/AP/imagesAP2/reprod/menstcyc.jpg

http://4.bp.blogspot.com/_15-2o9FAeCE/SBiYrNuBFEI/AAAAAAAAASc/9l1Usb-KOrI/s400/300px-MenstrualCycle.png

http://2.bp.blogspot.com/_UDpNzFLK85g/Sepl1zlqm0I/AAAAAAAAAJE/QEiQJB3zmxk/s400/menstrual+cycle.gif

====Ovulation====
*As the granulosa cells of the secondary and mature follicle produce more and more estrogen, more and more LH is released from the anterior pituitary gland (adenohypophysis, pars distalis).
*Ovulation events include:
**Breakdown of the cumulus oophorus, thus the oocyte floats freely in the antrum and follicular fluid.
**Weakening of the ovarian stroma:
***Proteolytic enzymes like '''collagenase''' disrupt the stromal connective tissue.
***Granulosa cell connections weaken
***Local ischemia causes a pale spot on the surface of the ovary called a '''stigma'''.
***Follicular wall ruptures releaseing an oocyte with the corona radiata and zona pellucida surrounding.

====The corpus luteum====
*LH causes granulosa cells to become '''granulosa lutein cells''' and theca cells to become '''theca leutein''' cells.
**Granulosa lutein cells develop the morphology of a secretory cell and '''actively produce progesterone'''.
**Note that '''the production of progesterone by the granulosa lutein cells is necessary for implantation''' of the embryo.
*LH causes theca cells to become '''theca lutein cells'''.

*If pregnancy does not occur, the corpus luteum is called the '''corpus luteum of menstruation'''.
**Therefore, '''progesterone from the corpus luteum is self limiting'''.
**That is, the corpus luteum will bring about self-demise via progesterioen inhibition of pituitary-LH unless chorionic gonadotropin is generated by the placenta.

*If pregnancy occurs, the corpus luteum is called the '''corpus luteum of pregnancy'''.
*Recall that trophoblasts of the placenta produce chorionic gonadotropin which maintains the corpus luteum (even though LH drops because of high progesterone levels).
**hCG is the hormone used to test for pregnancy.
*Granulosa cells of the corpus luteum of pregnancy produce '''relaxin''' which has a smooth-muscle relaxing effect (histo says "during parturition", wikipedia says "during gestation").
**'''Relaxin opposes the pro-parturition actions of oxytocin'''; that is, it keeps the smooth muscle of the uterus relaxed.
**Relaxin '''targets the fibrocartilage of the pubic symphysis''' to increase articulation.
**Note that physio notes say that the role of relaxin in pregnancy is unclear.

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/corpus%20leutum.jpg

====Follicular atresia====
*Follicular atresia generates a long-lasting, scar-tissue structure called the '''corpus albicans'''.
*The zona pellucida remains (bright pink) and a wavy line (the basement membrane, called the '''glassy membrane''').

http://zoomify.lumc.edu/histonew/female/female/dms174/27.gif

===The uterine tubes===
*The uterine tubes are muscular tubes that extend from the ovary on the posterolateral wall of the abdomen to the medioventral aspect of the abdomen and the lateral aspect of the uterus.
*As the oviducts progresses distally, there are fewer involdings.

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab29/IMAGES/FEML26.JPG

http://www.1cro.com/Diversity/extovary.jpg

http://1.bp.blogspot.com/_YRaDDRB_iZc/TJtKfdjuPjI/AAAAAAAAKPA/lm57mEwumss/s1600/Oviduct-hen.jpg

http://www.jci.org/articles/view/29424/files/JCI0629424.f1/medium

====Layers of the oviduct====
*Like other epithelial tracts there are four major layers to the oviduct (from inner to outer): mucosa, lamina propria, muscularis, and serosa.
*'''Secretions from the oviduct promote sperm activation'''.
Does this refer to capacitation?

http://www.kumc.edu/instruction/medicine/anatomy/histoweb/female/small/Fem10s.JPG

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2020/2020%20Exam%20Reviews/Exam%205/oviduct07-vessels.bmp

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2020/2020%20Exam%20Reviews/Exam%205/oviduct05.bmp

*Mucosa of the oviduct:
*The mucosa of the oviduct is comprised of '''columnar, ciliated''' epithelial cells.
**These columnar cells are '''secretory''' and are called '''Peg cells'''.
*Estrogen (from the corpus luteum) increases the height of the columnar cells.
*Progesterone (from the corpus luteum) increases the ciliary action of the columnar epithelial cells of the mucosa.

http://faculty.sdmiramar.edu/KPETTI/Bio160/TissueHistology/SimCol-Oviduct.jpg

http://faculty.une.edu/com/abell/histo/oviduct.jpg

http://www.ansci.wisc.edu/jjp1/ansci_repro/lec/lec1/female_images/images_nolabel/oviduct%20epithelium.jpg

http://faculty.une.edu/com/abell/histo/ampovidw.jpg

*Lamina propria:
*The lamina propria of the oviduct is '''highly vascularized'''.

http://faculty.une.edu/com/abell/histo/oviduct2w.jpg

*Muscularis:
*As with so many muscularis layers, there is an '''inner circular''' and '''outer longitudinal''' layer.
*The two layers of the muscularis are '''interwoven'''.

http://animalsciences.missouri.edu/courses/4314/microscope_slides/ampulla.jpg

*Serosa:
*The serosa is a '''true serosa''' because it is lined with mesothelium.

http://instruction.cvhs.okstate.edu/histology/fr/images/OviductBp12.jpg

http://neuromedia.neurobio.ucla.edu/campbell/female/wp_images/56_oviduct_LP.gif

http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/Oviductlx1XL.jpg

===The uterus===

====Layers of the uterine wall====
*Like the oviducts and other epithelial tracts, there are '''four tissue-type layers to the uterus''' which make up '''three functional layers''' of the uterus.
*The epimetrium is composed of serosa and adventitia and is a form of '''mesothelium''' as one would expect to cover surface of organs that faces the inside of the abdomenal cavity.

*Note that the cervix is histologically distinct from the rest of the uterus; we will revisit this.

http://people.fmarion.edu/tbarbeau/oviduct_histo.jpg

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/1%20uterus.jpg

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/Uterues%202.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab28/IMAGES/FEML20.JPG

http://www.siumed.edu/~dking2/erg/images/RE018b.jpg

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/uterus1.jpg

http://www.ouhsc.edu/histology/Glass%20slides/21_01.jpg

===The uterine cycle===
*From [http://editthis.info/iusmphysiology/?title=Female_reproductive_physiology&section=20#Mentrual_cycle physio notes]:
*The '''proliferative stage''' is characterized by '''endometrium hypertrophy''' and formation of '''spiral arteries'''.
**So as the ovary is maturing its follicle, the uterus is regenerating it's surface (where the egg will implant) and increasing vascular access to the surface.
*The '''secretory stage''' is characterized by '''coiling of glands''', '''secretion of mucus''', '''tortuous arteries''', and '''peak thickness of the endometrium'''.
**So, as the ovary has shed an ovum and is now increasing hormone production via the corpus luteum, the uterus is using glands and arteries of the uterus to modify the uterine microenvironment to the optimal conditions for egg implantation.
*The '''ischemic stage''' is characterized by '''arterial constriction''', '''decreased blood flow''', and '''increased prostaglandins'''.
**So as the ovary has reached its lowest levels of hormone production, the uterus is decreasing nutrition to the endometrium and allowing the mucosa to undergo necrosis by ischemia.
*The '''menstrual stage''' is characterized by '''desquamation of the endometrium'''.
**So as the ovary has reached its lowest levels of hormone production, the uterus is shedding its endometrium.

====Uterine vasculature====
*The uterus is supplied by '''arcuate arteries that run along the myometrium''' layer and by '''radial arteries that cross into the endometrium'''.
*The radial arteries give off '''straight (basal) arteries that supply the endometrium basalis'''.
**Note that the endometrium is divided into two layers: the '''endometrium basalis''' is a constant, mostly unchanging layer while the '''endometrium functionalis''' cycles through generation (proliferation) and shedding.
**'''There is no structural marker to distinguish between the basalis and the functionalis of the endometrium'''.
*'''Spiral (coiled) arteries''' are heavily muscular, generated during the endometrial cycle, and bridge the radial arteries into the endometrial functionalis.
**Of special note are the vascular structures nearest the lumen of the uterus called '''lacunae'''.

http://upload.wikimedia.org/wikipedia/commons/thumb/0/08/Uterine_arterial_vasculature.svg/220px-Uterine_arterial_vasculature.svg.png

====Uterine endometrium====
*The endometrial mucosa contains '''uterine glands'''.
**Uterine glands are tubular with many branches.
**Uterine glands contain both '''ciliated''' and '''non-ciliated''' cells.

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection3/FemaleRepTract03_files/image006.jpg

====Histological changes in the uterine cycle====
*The phases are divided over approximately 28 days: menstruation (days 1-5), proliferation (6-15), secretion (16-17), ischmia (18-28).

*Menstruation:
**Note that '''the base of the uterine glands''' remain visible in the endometrium basalis.
**http://upload.wikimedia.org/wikipedia/commons/thumb/0/08/Uterine_arterial_vasculature.svg/220px-Uterine_arterial_vasculature.svg.png

*Proliferative stage:
**The proliferative stage is '''driven by estrogen''' produced by the developing follicle.
**In addition to gland coiling, '''spiral arteries develop''' in the thickening endometrium.
**'''Cells of the proliferative endometrium accumulate glycogen'''.

*Secretory stage:
**The secretory stage is '''driven by progesterone''' from the corpus luteum.
**The secretory stage is characterized by '''release of glycoprotein-rich products''', '''swelling and torture''' of the glands and spiral arteries, and '''accumulation of fluid in the stroma''' of the endometrium.

*Ischemia:
**The ischemic stage is characterized by '''constriction of the coiled arteries''', '''stromal fluid loss''', and '''lymphocyte / macrophage cell invasion'''.
***When the corpus luteum degenerates and progesterone levels drop, local prostaglandins are released into the endometrium, the vessels constrict, and blood flow is arrested causing ischemia.
**The coiled arteries dilate and constrict intermittently which causes ischemia, cell lysis, a weakened stroma, bursting vessles, and debridement of the functionalis.
***The arteries both restrict oxygen (constriction) to cause cell death but also to flush away the dead tissue (dilation).

====Uterine cervix====
*As mentioned before, '''the cervix is histologically distinct''' from the rest of the uterus.

*The cervical myometrium:
**'''The cervical myometrium has '''less smooth muscle''' and '''abundant collagenous connective tissue with elastic fibers'''.

*The cervical endometrium:
**The cervical endometrium has '''denser stroma''', '''simple columnar epithelium''', '''branched, dilated, cyst-forming glands''', and longitudinal mucosal folds called '''plicae''' (plicae palmatae).
***Cervical glands can form cysts called '''Nabothian cysts'''.

*The cervical mucus:
**Mid way through the cycle (think ovulation and sperm-friend environment) the mucus is '''watery''', contain '''lysozyme''' (bacterioalcidal), and promotes sperm motility.
***This sperm-friendly mucus is '''estrogen-stimulated'''.
**Late in the uterine cycle (think corpus luteum and potential implantation) the mucus is viscous and '''progesterone-stimulated'''.
**During pregnancy the mucus is particularly thick (think lots of progesterone) and thus protective of the fetus.
***One may look for the loss of this dense mucus plug as a sign that parturition is commencing.

http://www.siumed.edu/~dking2/erg/images/RE052b.jpg

http://www.netterimages.com/images/vtn/000/000/007/7987-150x150.jpg

http://www.gfmer.ch/Books/Cervical_cancer_modules/Images/MI7.jpg

http://www.fpnotebook.com/_media/GynCervicalColposcopyAcetowhite1.jpg

http://missinglink.ucsf.edu/lm/IDS_106_LowerGI/IDS_images_downsized/fig10.jpg

=====The ectocervix=====
*The ectocervix is also called the '''portio vaginalis'''.
*At the ectocervix the '''epithelium changes from columnar (cervix) to stratified squamous (vagina)''' abruptly.
*Normal ecotcervix:
**http://pathweb.uchc.edu/eAtlas/Images/GYN/5764b.gif http://pathweb.uchc.edu/eAtlas/Images/GYN/5766b.gif
*http://www.nature.com/nri/journal/v8/n6/images/nri2302-f1.jpg
*http://www.arabicobgyn.net/doc/CERVIX_files/image010.gif
*http://www.path.cam.ac.uk/Abnormal/NP_Neoplasia/ME_Metaplasia/CX_Cervix/A_NP_ME_CX_01small.jpg

===Vagina===
*The mucosa is characterized by stratified, squamous, non-keratinized epithelium.
**The epithelial cells of the vagina--like those of the uterus--accumulate glycogen upon estrogen signaling.
*The vaginal lamina propria has '''no glands''', patches of '''lymphocytes''', and can have folds.
**Recall, however, that the uterus does have glands in the lamina propria.
*The vaginal muscularis has '''interlacing bundles of smooth muscle'''.

http://www.lab.anhb.uwa.edu.au/mb140/CorePages/FemaleRepro/Images/vag02he.jpg

http://www.ansci.wisc.edu/jjp1/ansci_repro/lec/lec1/female_images/images_label/vagina(l).jpg

http://www.ouhsc.edu/histology/Glass%20slides/22_05.jpg

http://www.ouhsc.edu/histology/Glass%20slides/23_04.jpg

===Mammary glands===
*The mammary glands are made of a compound tubuloalveolar system; that is, there are alveoli that take part in the secretory component and there are ducts that take part in the transport component.
**A group of about 20 glands forms a '''mammary lobule'''.
*Secretory component:
**Milk is generated by '''cuboidal epithelial cells''' arranged in '''alveoli'''.
**The '''myoepithelial cells arise from the cuboidal epithelial cells'''.
**Plasma cells are found in and around the alveoli in order to '''generate IgA'''.
*Mammary ducts:
**The epithelium that lines the ductule system is '''stratified cuboidal'''.
**There is a significant amount of '''smooth muscle between the ducts and sinuses'''.
**Most breast cancers arise from lactiferous duct cells.

https://lh3.googleusercontent.com/_WdFQawAlzZM/TW_UdyeIT0I/AAAAAAAAAoA/pvQX_ngLS0M/s800/F22_27.jpg

http://www.nature.com/nrc/journal/v2/n2/images/nrc721-f1.jpg

http://www.genericlook.com/img/uploads/anatomy/mammary-glands.jpg

http://neuromedia.neurobio.ucla.edu/campbell/skin/wp_images/161_myoepithelial.gif

http://www.breast-cancer.ca/images/breast-myoepithelial-cells.jpg

http://neuromedia.neurobio.ucla.edu/campbell/glands/wp_images/myoepithelial%20cells.jpg

http://img.medscape.com/pi/emed/ckb/pediatrics_cardiac/1331339-1331345-1835675-1835738.jpg

====Mammary glands at puberty====
*When '''estrogen''' increases at puberty ('''and prolactin is present'''), '''alveolar buds develop and regress''' with each ovarian cycle.

====Mammary glands in pregnancy====
*Upon pregnancy, estrogen is found at high levels '''along with prolactin, placental lactogen, and progesterone''' and therefore the alveolar ducts and alveoli fully develop.
*'''Lactogenesis is regulated by estrogen, progesterone, and prolactin'''.
**This makes sense because estrogen and progesterone increase throughout pregnancy and once progesterone and estrogen drop (at parturition), prolactin has its most potent effect.
*'''Galactogenesis is maintained by prolactin and oxytocin'''.

http://www.as.miami.edu/chemistry/2086/chap28/NewChap28-Female_files/image010.jpg

https://lh4.googleusercontent.com/_WdFQawAlzZM/TaOd4WAHBbI/AAAAAAAAAuc/9Hh5a4tSLKE/s800/mammary_gland_comparison.jpg

====Breast milk====
*The first milk generated is called colostrum; colostrum is '''lactoprotein- and immunoglobulin- rich''' and '''lipid-deficient'''.
*Lactation can generate 1100 to 2100 ml every day.
**Note that physio said 800-1200 ml / day.
*These cuboidal epithelial cells use several secretion mechanisms to release their products.
**'''Merocrine secretion''' is used to secrete casein, alpha-lactalbumin, and PTH-RP (protein, basically).
**'''Apocrine secretion''' is used to secret TAGs and cholesterol.
**'''Exocytosis''' is used to secrete lactose.
**'''Transcytosis''' (from adjacent plasma cells) is used to secrete dimeric IgA.

====Regulation of milk let-down====
*Note that '''afferent CNS signals also stimulate dopamine inhibition''' such that '''prolactin is increased''' which stimulates the cuboidal epithelial cells of the alveoli to increase milk production.
*Note that '''multiple neuroendocrine factors''' have been found besides oxytocin to '''relax the smooth muscle sphincter''' between the lactiferous ducts and the lactiferous sinuses.

===Summary===
*Estrogens increase as the follicle develops and:
**inhibit FSH at the pituitary
**stimulate LH at the pituitary
*LH promotes corpus luteum formation
*Corpus luteum produces progesterone and estrogen
**Estrogen causes uterine proliferation phase
**Progesterone causes uterine secretory phase
*Progesterone inhibits LH

==Male reproductive==

===Anatomy review===
*The '''mediastinum testis''' is where the vessels (blood and lymphatics), nerves, and efferent duct enter and exit the testis.
**Note that the mediastinum testis is connective tissue while rete testis is a collecting tubule tissue.
**The '''tunica propria''' is the outer wall of the seminiferous tubule and is made of '''smooth muscle and fibroblasts'''.

===Seminiferous epithelium===

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection3/TestesandSperm03_files/image002.jpg

===Spermatogenesis===
*Primary spermatocytes are in the prophase of meiosis 1 and stick around for 20 days.
*Secondary spermatocytes are relatively short-lived.

*Cells of the basal compartment: type A and type B spermatogonia, primary spermato'''cytes'''
*Cells of the adlumenal compartment: secondary spermatocytes, spermatids, spermatozoa

*Cells and processes: type A spermatogonia undergo mitosis to become ... type B spermatogonia undergo mitosis (and differentiation) to become ... primary spermatocytes undergo meiosis 1 ... secondary spermatocytes undergo meiosis 2 ... spermatids undergo morphologic modification (differentiation) ... spermatozoa.
**'''Spermatocytogenesis''' includes all the steps that generate an increasing number of cells (that is, type A spermatogonia through generation of secondary spermatocytes); this makes sense because of the name "cyto" = cell and genesis = "origin of".
**'''Spermiogenesis''' is the converse of spermatocytogenesis: spermeiogenesis is the maturation of existing cells into spermatozoa (from the secondary spermatocyte stage to the spermatozoa stage).

http://image.wistatutor.com/content/reproduction-in-animals/spermatogenesis-and-spermiogenesis-stages.jpeg

http://image.wistatutor.com/content/reproduction-in-animals/spermatogenesis-spermiogenesis-process.jpeg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab27/IMAGES/MREPL08.JPG

====Mitosis and Meiosis====

====Spermiogenesis====
*Spermiogenesis is characterized by morphological changes to the spermatid, that is the specialization / differentiation of the spermatid into the spermatozoa:

*Golgi phase:
**The enzymes like hyaluronidase and trypsin-like protease accumulate at one pole of the nucleus in a vesicle (which will become the acrosome).

*Acrosomal phase:
**The cell '''rotates such that the axoneme faces the lumen'''.

*Maturation phase:
**The maturation phase is characterized by motile apparatus development and the capacity to fertilize.
**Note that '''during the maturation phase, the spermatids are not yet motile or fertile'''.

http://www.ccs.k12.in.us/chsBS/kons/kons/images/spermiogenesis.jpg

===Sertoli cells===
*Sertoli cells are characterized by being '''tall, columnar''' epithelial cells with a '''large, indented euchromatic nucleus''', and lots of eosinophilic cytoplasm.
*Neighboring Sertoli cells within a region have '''gap junctions which suggest that Sertoli cells are coordinated within their region'''.

====Blood testis barrier====
*Sertoli cells of the seminiferous epithelium form tight junctions between one another to keep immunoglobulins in the blood from entering the lumen of the tubule.
**Note that these '''tight junctions of the Sertoli cells are on the ''lumenal'' side of the spermatogonia'''.
**These tight junctions define the two compartments: basal compartment and adlumenal compartment.

====Sertoli function stimulated by FSH====
*Recall that the anterior pituitary releases FSH which binds to the FSH receptor on Sertoli cells.
*FSH signaling on Sertoli cells causes phagocytic activity and production of several secretions.
*Secretions of the Sertoli cells:
**Activin and Inhibin: stimulate and inhibit the anterior pituitary cells to release FSH.
**Androgen binding protein (ABP): secreted into the lumen of the seminiferous tubule, binds up and concentrates testosterone.
**Tubular fluid: lubrication.

===Leydig cells===
*Note that '''Leydig cells do not secrete activin or inhibin'''.
*Leydig cells are found in clusters in the '''peritubular interstitium''' of the testis, between the seminiferous tubules.
**Recall that Leydig cells are often found near capillaries.
*Leydig cells are characterized by eiosinophilicism, lots of sER, mt with tubular cristae, and '''a lack of secretory vesicles'''.
**Regarding lots of sER, recall that steroids are generated in sER.
**Regarding a lack of secretory vesicles recall that steroids can pass directly through the membrane and therefore need not vesicular secretion.
**By transmission EM, one can also discern '''crystalline inclusions'''.

*Leydig cells are "transiently" active during development and then initiate full activity at puberty.

===Segments of the male reproductive tract===
*Seminiferous tubules -> tubuli recti (straight tubules) -> rete testis -> efferent ductules -> epididymal ducts -> ductus deferens (vas deferens) -> ejaculatory duct -> prostatic uretral -> membraneous urethra -> penile urethra.

Where do basal cells and principal cells start?

*Straight tubule (tubuli recti)
**Contributes to fluid
**Cuboidal to columnar
**'''Contains Sertoli cells'''

*Rete testis
**Contributues to fluid
**Has an '''irregular epithelial morphology''': squamous, cuboidal, columnar.
**Has a '''fibrous stroma'''

*Efferent ductule
**Like the rete testis, the efferent ductule has an irregular epithelial morphology and also has '''ciliated, pseudostratified cells'''.
***These ciliated pseudostratified cells are called '''principal cells''' and are found as clusters of columnar cells surrounded by short cells.
***These cells are '''the only ciliated cells of the male genital tract'''; it even makes a bit of sense that these are ciliated because they are passing through a sturdy connective tissue structure.

*Ductus epididymis
**The ductus epididymis is characterized by an pseudostratifed columnar epithelium, '''stereocilia''', and a '''prominent muscularis layer'''.
**'''Basal cells are regenerative.'''
**'''Principal cells are secretory / absorptive.'''
**The ductus epididymis has a prominent muscularis layer that thickens distally and changes from just a circular layer to an '''inner circular and outer longitudinal layer'''.
**The functions of the ductus epididymis: absorb 90% of the tubular fluid, secrete factors that mature and capacitate sperm, and phagocytize cellular debris.

*Ductus deferens (vas deferens)
**The ductus deferens is characterized by a pseudostratified columnar epithelium, '''abundant sympathetic innervation''', and '''three layers to the muscularis'''.
**The ductus deferens is pseudostratified (like the efferent ductule and ductus epididymis) and has stereocilia (like the ductus epididymis).
**The muscularis has now added an inner longitudinal muscle layer to the ductus epididymis's inner circular and outer longitudinal.
**The sympathetic innervation will be important for ejaculation which is facilitated by contraction of the ductus deferens's muscularis.
***Recall that Point and Shooting require Parasympathetic and Sympathetic innervation.

*Ejaculatory duct

*Membranous urethra
**The membranous urethra is characterized by a '''pseudostratified epithelium that transitions to a stratified columnar epithelium.'''

*Penile urethra
**The penile urethra is characterized by a '''pseudostratified epithelium that transitions to a stratified columnar epithelium''', perhaps continuing on to '''stratified squamous epithelium at the top'''.
**The penile urethra is also characterized by the presence of '''urethral glands''' which are clusters of mucus cells in the mucosa.

{| border="1"
|-
! Section
! Epithelium
! Appendages
! Muscularis
|-
| Seminiferous tubule
| stratified
| none
| none
|-
| Tubuli recti
| cuboidal -> columnar
| none
| none
|-
| Rete testis
| irregular: squamous, cuboidal, columnar
| none
| none
|-
| Efferent ductule
| pseudostratified
| cilia
| none
|-
| Ductus epididymis
| pseudostratified
| sterocilia
| circular -> circular (inner) + longitudinal
|-
| Ductus deferens
| pseudostratified columnar
| stereocilia
| longit (inner) + circular + longit
|-
| Ejaculatory duct
| pseudostratified columnar
| ?
| ?
|-
| Prostatic urethra
| pseudostratified -> simple columnar
|
|
|-
| Membranous urethra
| pseudostratified -> stratified columnar
| none
| longit (inner) + circular + longit
|-
| Penile urethra
| pseudostratified -> stratified columnar -> stratified squamous
| none
| longit (inner) + circular + longit
|}

===Accessory glands of the male reproductive tract===

====Seminal vesicles====
*Seminal secretions are rich in fructose (for energy), prostaglandins, amino acids, and ascorbic acid.
*The seminal vesicle has plenty of '''smooth muscle''' with which to force this secretion out into the ejaculatory duct.
*Seminal vesicle function and growth is mediated by testosterone.
*The vesicles are blind-ended pouches near the prostate and ductus deferens.
*'''Seminal vesicles are lined with pseudostratified columnar epithelium'''.
**This makes sense because they pump semen out into the GU tract at the ductus deferens and ejaculatory duct, both of which are pseudostratified.
*The seminal vesicles have '''mucosal arches''' which are highly folded, convoluted walls.

====Prostate====
*The prostate generates a secretion that becomes part of the semen and '''serves to condition the environment of the famale GU tract'''.
*The '''fribromuscular stroma''' surrounding the prostate is important for proper discharge of prostatic secretions during ejaculation.
*Zinc inhibits macrophage activity.
*Fibrinolysin inhibits clot formation in the uterus.
*The prostate as a gland has alveoli connected via tubules; the tubules converge to generate a '''group of ducts''' that dump into the '''urethral crest'''.
**The urethral crest receives the ejaculatory ducts and becomes the prostatic urethra.
**The epithelium within the gland is irregular: pseudostratified to simple columnar.
*'''Corpora amylacea''' is a concentration of glycoprotein-rich secretion in the lumen of the gland that stains eosinophilic (because of the "protein-rich" part).

*The prostate has three concentric-like zones: central zone, transitional zone, and peripheral zone.
*The '''central zone''' of the prostate is the most medial and contains primarily '''periurethral mucosal glands'''.
**The central zone often stains the lightest of the zones.
*The '''transitional zone''' of the prostate is the middle zone and contains '''periurethral submucosal glands'''.
**Note that the '''central and transitional zones''' are most commonly associated with '''benign prostatic hypertrophy (BPH)'''.
*The '''peripheral zone''' of the prostate is the outer zone, contains the '''main glands''', is called the '''prostate proper''', and is commonly involved with '''malignancies'''.
**The peripheral zone is often involved with '''prostate cancer'''.

====Bulbourethral glands====
*The bulbourethral glands produce a secretion for lubricating the male GU tract for ejaculation.
*The secretion of the bulburethral gland is clear and viscous.

===Ejaculation sequence===
*Ejaculation has a particular series of events regarding all these secretions:
**Bulbourethral glands discharge to lubricate.
**Prostate releases contents (via contraction of the fibromuscular stroma).
***Recall that the prostate's secretions serve to condition the female GU tract.
**The ductus deferens receives sympathetic stimulation to contract its muscularis (1->2 layers), thus pushing spermatozoa into the urethra.
**Seminal vesicles discharge their contents thus clearing the urethra by pushing semen distally.

*ID straight tubules by the presence of Sertoli cells.
*Ductus epididymis has very tall cells with cilia.
*Ductus deferens ID by stereocilia and three layers of muscle.
*Seminal gland: mucosal arches
*Prostate is ID'd by '''corpora amylacea''' (a concentration of glycoprotein-rich secretion in the lumen of the gland that stains eosinophilic).

==Skin==

===Describe the basic histological structure of the skin===

http://www.lab.anhb.uwa.edu.au/mb140/corepages/integumentary/Images/skthick0021he.jpg

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%202%20Review/epidermal_ridges1.gif

===Identify the cell layers that constitute the epidermis===
*Also, the granulosa and corenum layers are thicker in "thick skin".

http://www.greenfoodsonline.co.nz/blog/wp-content/uploads/2009/07/epidermal-layers.jpg

http://faculty.stcc.edu/AandP/AP/imagesAP1/skin/skin.jpg

====Stratum basale====
*The cells of the basal layer are connected to the basement membrane via '''hemidesmosomes'''.

http://employee.lsc.edu/faculty/BrianBich/Picture%20Library/Anat-Phys%20I%20(Biol%201140)/Integument/Thick%20Skin%20-%20Tutorial/F%20-%20Thick%20Skin%2040X-3-Epidermal%20Layers.jpg

====Stratum spinosa====

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Integumentarysystem03_files/image004.jpg

https://lcsdanatomyphysiology.wikispaces.com/file/view/epidermis.png/194354678/epidermis.png

http://lecannabiculteur.free.fr/SITES/UNIV%20W.AUSTRALIA/mb140/CorePages/Integumentary/Images/skn40he.jpg

====Stratum granulosmum====
*The granule-containing cells of the granulosum contain '''filaggrin, and intermediat filaments''' that help to form the '''tonofibrils''' along with '''keratin'''.
**Note that these granules are called '''keratohyline granules'''.
**Kertohyline granules have no membrane.
*The cells of the granulosum are flattened polygonal cells--found in 3 to 5 layers.
**Just like "lamellae" in chloroblasts, lamellar granules have a sort of stacked-bags look
*Labellar graunules cannot be seen in light microscopy.
**http://www.bioone.org/na101/home/literatum/publisher/bioone/journals/content/bire/2000/00063363-63.6/biolreprod63.6.1706/production/images/small/i0006-3363-63-6-1706-f06.gif
**http://biologiedelapeau.fr/IMG/jpg/lamellar-granules-3web.jpg

http://bestofbothworldsaz.com/wp-content/uploads/2010/09/SkinLayers.jpg

http://www.dermpedia.org/files/u49/Epidermolytic_hyperkeratosis_stp5.jpg

http://www.virtualmedicalcentre.com/uploads/VMC/Anatomy/oral_mucosa_450.jpg

http://www.anatomyatlases.org/MicroscopicAnatomy/Images/plate136.jpg

====Stratum lucidum====
*The lucidum (ironically) stains darkly.

http://ouhsc.edu/histology/Glass%20slides/43_09.jpg

====Stratum corneum====

http://employee.lsc.edu/faculty/BrianBich/Picture%20Library/Anat-Phys%20I%20(Biol%201140)/Integument/Thick%20Skin%20-%20Tutorial/D%20-%20Thick%20Skin%2040X-1-Epidermal%20Layers.JPG

====Dermo-epidermal junction====
*Recall, too, that the epidermal cells of the basal layer are connected to the basement membrane via hemidesmosomes.
*The dermis contains lots of '''type 4 collagen'''.
*The superficial aspect of the dermis that is attached to the basement membrane of the epidermis is the '''lamina densa'''.
*The lamina densa of the dermis and the basement membrane of the epidermis are connected via '''anchoring filaments''' and '''anchoring fibrils'''.
**Note that '''anchoring filaments are composed of type 7 collagen'''.

https://steinbachs.org/download/attachments/4686497/Fig18-3c.jpg

===Describe the cellular components of the epidermis and their functions===
*There are four major cells of the epidermis: keratinocytes, melanocytes, langerhan cells, and merkel cells.

https://lh6.googleusercontent.com/_WdFQawAlzZM/TaRKusxrDOI/AAAAAAAAAu4/yid3LHxB7Pw/s800/epidermal_cells.jpg

====Keratinocytes====

http://www.nanogen.org/en/images/nano-skincell-life.gif

====Melanocytes====
*Melanocytes are '''derived from neural crest cells''' and function to generate the pigment melanin which protects cells from UV damage.
*Melanosomes are said to "mature" as they are produced; they turn from a light, circular shape to a dense cucumber shape.

http://faculty.une.edu/com/abell/histo/thickskin1w.jpg

http://autoimmune.pathology.jhmi.edu/images/Skin2.jpg

http://www.ccs.k12.in.us/chsBS/kons/kons/images/Skin_tws_16_02.jpg

http://skinipedia.org/images/photos/melanocyte2.jpg

http://www.lab.anhb.uwa.edu.au/mb140/corepages/integumentary/Images/labmi040he.jpg

http://www.ratbehavior.org/images/MyosinTravelBig.jpg

http://www.nature.com/nrm/journal/v8/n10/images/nrm2258-f4.jpg

====Langerhans cells====
*Langerhans cells reside primarily in the '''spinosum''' layer (think "spines and chinese are for killing bad guys!''').

http://www.technion.ac.il/~mdcourse/274203/slides/Skin/6-Langerhans%20Cells.jpg

http://www.nature.com/nm/journal/v13/n3/images/nm0307-245-F2.gif

====Merkel cells====
*Merkel cells (like melanocytes) are found primarily in the basal layer, which makes sense because they are a sensation cell that needs to be near a nerve ending.
**Note that '''Merkel cells are found primarily in thick skin''' where touch needs to be highly sensitive.
*Merkel cells, along with the '''expanded terminal bulb''' of afferent, myelinated nerves, form the '''Merkel's corpuscle''' which detects touch as a '''mechanoreceptor'''.
*The Merkel cells contain dense-cored '''neurotransmitter granules'''.

http://neuromedia.neurobio.ucla.edu/campbell/skin/wp_images/cell%20types.jpg

===Describe the structural organization of the dermis===

====Papillary layer of the dermis====
*Connective tissue of the papillary layer is composed of '''type 1 collagen''', '''type 2 collagen''', and '''elastic fibers.

====Reticular layer of the dermis====
*The reticular layer is composed of '''type 1 collagen''' and '''regularly oriented elastic fibers (called Langer's lines)'''.

http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology%20Glossary/Glossary%20Histo%20Images/Papillary_vs_Reticular_Dermis_10x-208.jpg

http://bestofbothworldsaz.com/wp-content/uploads/2010/09/SkinLayers.jpg

http://www.biology-online.org/user_files/Image/Anatomy/AN-fibroblastF02.gif

http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/dermis1.jpg

http://www.bu.edu/histology/i/08203loa.jpg

http://farm4.static.flickr.com/3412/3195805407_be3ba25e62_o.jpg

===Identify other structures in the skin===

====Vessels====

http://www.netterimages.com/images/vpv/000/000/056/56826-0550x0475.jpg

http://www.netterimages.com/images/vpv/000/000/056/56826-0550x0475.jpg

====Sensory receptors====
*There are four types of sensory receptors in the integumentary system (skin): free nerve endings, pacinian corpuscles, meissner's corpuscles, and ruffini's corpuscles.

=====Free nerve endings=====
*Free nerve endings are found in the '''stratum granulosum''' and detect '''fine touch, heat, and cold'''.
*http://library.thinkquest.org/05aug/00386/touch/freenerveendings.gif
*http://webanatomy.net/histology/neural/free_nerves.jpg

=====Pacinian corpuscles=====
*Pacinian corpuscles are nerve endings surrounded by an oval encapsulation of connective tissue in the '''deeper dermis and hypodermis'''.
*Think '''maraca shaped and all that vibration!'''
*http://library.thinkquest.org/05aug/00386/touch/paciniancorpuscule.gif
*http://www.siumed.edu/~dking2/intro/images/IN039b.jpg
*http://kentsimmons.uwinnipeg.ca/cm1504/15lab42006/lb4pg9_files/image012.jpg
*http://www.esg.montana.edu/esg/kla/ta/pacinian.jpg
*http://download.videohelp.com/vitualis/med/pacinian_corpuscle.jpg
*http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_&_Physiology/A&P202/Special_Senses/Pacinian_corpuscles_PC271521lbd.JPG
*http://www.sci.uidaho.edu/med532/images/receptor/pac_corp2.jpg

=====Meissner's corpuscles=====
*Meissner's corpuscles are found in the papillary layer of the dermis and are sensitive to '''low frequency stimuli'''.
**Doesn't "meissner" sound like an old miser with a low, grumpy voice?
*Meissner's corpuscles are shaped like tapered '''m'''itochondria and are oriented perpendicular to the skin.
*http://library.thinkquest.org/05aug/00386/touch/meissnercorpuscule.gif
*http://www.starsandseas.com/SAS_Images/SAS_Physiol_Images/SAS%20neuropics/Neurons_02.jpg
*http://www.siumed.edu/~dking2/bluehist/BH011b.jpg
*http://www.siumed.edu/~dking2/intro/images/IN038b.jpg
*http://www.cytochemistry.net/microanatomy/nerve/nerve12.jpg
*http://cmdi.medicine.dal.ca/Anat5217/Lab9/26LHMC.JPG
*http://ouhsc.edu/histology/Glass%20slides/101_04.jpg
*http://webanatomy.net/histology/neural/meissners.jpg
*http://kcfac.kilgore.cc.tx.us/mobleypageap2/nerve%20tisues/Meissner%27s%20corpuscle%20400x%20fireworks.jpg

=====Ruffini's corpuscles=====
*Ruffini's corpuscles are simple mechanoreceptors and have an "elongated fusiform shape".
*http://library.thinkquest.org/05aug/00386/touch/ruffiniending.gif

=====Sensory receptor images=====
http://www.neurobiography.info/teaching/images/somatosensory/cutaneous_receptors_hairy_vs_nonhairy_1.gif

http://iupucbio2.iupui.edu/anatomy/images/Chapt18/FG18_03d-f.jpg

http://alexandria.healthlibrary.ca/documents/notes/bom/unit_6/unit6.images/peripheral%20mech%20fig%201.jpg

http://www.exploringnature.org/graphics/anatomy/sensory%20organs.jpg

http://www.anatomyatlases.org/MicroscopicAnatomy/Images/Plate123.jpg

http://www.karger.com/gazette/67/Elsner/images/skin.gif

http://www.healthyheating.com/Thermal_Comfort_Working_Copy/Images/Nerve_endings_labeled.gif

====Hair follicles====
*At the hair follicle a specialized layer called the '''glassy membrane''' (a type of basement membrane that is thickened and keratinized) separates the epidermis and the dermis.
*During hair growth, the follicle has a bulbous end at the deepest part.

*Hair has three layers (from outside in): cuticle, cortex, and medulla.
**The '''cuticle''' is the outer most and is comprised of '''squamous cells'''.
**The '''cortex''' contains '''cuboidal cells''' that differentiate into '''keratinized cells'''.
**The '''medulla''' contains large cells with '''vacuoles''' that are '''moderately keratinized'''.

*Sebum is released into the '''infundibulum''' which is a '''pilosebaceous canal''' that surrounds the base of the growing hair.
**http://www.follicle.com/img/follicle.jpg

http://elin.ttu.ee/mesel/Study/Subjects/0070BME/Content/BioElect/ProcPhen/7_kude_nahk_172-1x-Hair_follicle_labelled.jpg

http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/hair4F.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab15/IMAGES/INTEGL16.jpg

http://www.spencerclinic.co.uk/images/hair_pic2_large.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab15/IMAGES/DEEP%20HAIR%20FOLLICLE.jpg

http://amakabeautycare.files.wordpress.com/2010/03/hair-follicle-2.gif

http://www.raising-redheads.com/images/HairFollicleWikip.png

http://www.nature.com/nbt/journal/v18/n1/images/nbt0100_20_F1.gif

=====Phases of hair growth=====
*http://www.body-beauty-shop.com/images/hair-growth-cycle.jpg
*https://lh6.googleusercontent.com/_WdFQawAlzZM/TaRf2b28PvI/AAAAAAAAAvI/mWnIfw18-Bg/s800/F1.large.jpg

====Nails====
*The nail plate sit in the '''nail bed''' which is formed by the stratum basale and spinosum.

http://fungusfacts.com/wp-content/uploads/2009/10/nail-anatomy-diagram-cross-section.jpg

http://eulep.pdn.cam.ac.uk/~skinbase/Annotated_anatomy_of_the_mouse_nail/nail_labelled.jpg

http://classroom.sdmesa.edu/anatomy/Histologyphotos/Integument/Nail%201.jpg

http://www.footdoc.ca/Websit1.jpg

http://www.adiosnailfungus.com/images/anatomy_toenail.jpg

====Glands====

http://www.transtutors.com/Uploadfile/CMS_Images/21926_MODE-OF-SECRETION.JPG

http://medicalsolutions.medi-health.info/pilsinl/348.gif

=====Sebaceous glands=====

http://blog.dearbornschools.org/renkom/files/2010/12/sebaceous-gland.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab4/IMAGES/SEBACEOUS%20GLAND%20LABELED%20copy.JPG

http://www.nku.edu/~dempseyd/sebaceous%20gland%202%20good.jpg

http://www.pgbeautygroomingscience.com/assets/images/wosc/Chapter%201/Special%20Skin%202.jpg

http://www.lab.anhb.uwa.edu.au/mb140/corepages/integumentary/Images/sebaceous011he.jpg

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%202%20Review/ceruminous_gland.gif

=====Sweat glands=====

{|border="1"
|-
!Attribute
!Merocrine
!Apocrine
|-
|Secretion method
|Merocrine
|Apocrine '''and merocrine'''
|-
|Distribution
|Widely distributed
|Axillary and perineal regions only
|-
|Lumen size
|Small lumen
|Large lumen
|-
|Epithelial type
|Stratified cuboidal
|Simple cuboidal
|-
|Innervation
|Cholinergic fibers (ach)
|Adrenergic (cats)
|}

*Merocrine (eccrine):
**http://2.bp.blogspot.com/_o-Hb5F-QYCA/Sg1vjbjJ_pI/AAAAAAAABEs/ObmtIy1juXY/s400/180X10merocrine_sweat_gland.jpg
**http://www.technion.ac.il/~mdcourse/274203/slides/Skin/8-Eccrine%20Sweat%20Gland.jpg

*Apocrine:
**http://faculty.une.edu/com/abell/histo/apocrinesgw.jpg
**http://instruction.cvhs.okstate.edu/histology/HistologyReference/imagesco/skinglands3F.jpg

*Visual differentiation:
**Lumen size: small = merocirne, large = apocrine
**Density: denser = merocrine, lighter = apocrine
**Surrounding cells: myoepithelial cells surround merocrine to help secrete, apocrine don't necessarily have surrounding cells.

===Understand the mechanism of skin repair===

http://journals.cambridge.org/fulltext_content/ERM/ERM5_08/S1462399403005817sup005.gif

===Describe the histological findings in common skin diseases===

====Blistering====
*Abnormalities at the '''epidermis-dermis junction''' are called '''bullous pemphigoid'''.
**http://www.dermpedia.org/files/images/Bullous_pemphigoid_3.jpg
*Abnormalities of intercellular junctions are called '''pemphigus'''.
**http://library.med.utah.edu/kw/derm/mml/24820016.jpg

====Psoraisis====
*Psoriasis occurs when cells of the basal and spinosum layers demonstrate '''excessive proliferation''' and decreased cycle time which leads to '''increased thickness'''.
*One can identify psoriasis by the presence of '''nuclei in the stratum corneum'''; this finding is called '''parakeratosis'''.

http://www.drmihm.com/pictures/ACF1E7.jpg

http://www.webpathology.com/slides/slides/ExtGenitalia_Pagets1.jpg

http://dermatology.cdlib.org/126/unknown/eyelid/2.jpg

====Skin cancer====

http://www.aafp.org/afp/2004/1015/afp20041015p1481-f1.gif

=====Basal cell carcinoma=====
http://skincancer-fact.com/wp-content/uploads/2009/10/Basal_cell_carcinoma_-skin_cancer-picture.jpg

http://www.orlandoskindoc.com/Basal-cell-carcinoma-large.jpg

http://www.trihealth.com/ser/cancer/images/Basal_cell_carcinoma.jpg

http://www.healthpm.com/wp-content/uploads/2010/09/basal_cell_carcinoma.jpg

http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology%20Glossary/Glossary%20Histo%20Images/basal_cell_carcinoma_high_power.jpg

=====Squamous cell carcinoma=====
http://www.medicalook.com/diseases_images/squamous_cell_carcinoma.jpg

http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology%20Glossary/Glossary%20Histo%20Images/squamous_cell_carcinoma_in_situ_high_power.jpg

=====Malignant melanoma=====

http://www.prlog.org/10263280-malignant-melanoma.jpg

http://sunsafekids.tripod.com/sitebuildercontent/sitebuilderpictures/melanomas.jpg

http://www.nature.com/modpathol/journal/v18/n8/images/3800395f1.jpg

http://rad.usuhs.mil/derm/lecture_notes/Images/melanoma_histo.jpg

====Griscelli syndrome====
*Griscelli syndrome can result from a defective Rab27a protein which is part of the transport complex that moves '''melanosomes''' along '''microtubules''' for cyotocrine passage to other cells.

==The eye==

===Optical anatomy===

http://www.odec.ca/projects/2006/thog6n2/images/eye_2.gif

===Wall of the eye===

https://lh6.googleusercontent.com/_WdFQawAlzZM/TaR2ollnmXI/AAAAAAAAAvc/Ql2QplUuCDY/s800/eyeball_layers.jpg

===Eyeball function by component===

http://www.cytochemistry.net/microanatomy/eye/retina4.jpg

====Cornea====
*The layers (superficial to deep): epidermis, Bowman's membrane, stroma, Descemet's membrane, and endothelium.
*'''With age, Descemet's membrane''' decreases in transparency and leads to '''decreased light transmission'''.

http://www.ophthobook.com/wp-content/uploads/2007/12/video-cornealayers.jpg

http://www.lasik.md/img/learnAboutLasik/cornea.gif

http://www.uniteforsight.org/course/image/cornea.jpg

http://thalamus.wustl.edu/course/eye2.gif

=====Epithelium of the cornea=====
*The epithelium of the cornea is made of '''stratified, squamous, non-keratinized epithelium'''.

http://www.dartmouth.edu/~rpsmith/lens.gif

http://www.bu.edu/histology/i/08006loa.jpg

http://library.thinkquest.org/28030/media/schlemm5.gif

http://1.bp.blogspot.com/_kaQ5P19FVgk/THl4ddhkNnI/AAAAAAAAG20/PtY3YVnIgpE/s400/Canal_de_Schlemm.JPG

=====Stroma of the cornea=====
*The stroma is series of layers of '''fibrocytes, proteoglycans, and ECM fibers''' with alternately oriented collagen fibers.
**Note that '''collagen of the stroma is of type 1 and 5''' and are '''non-fibrillar'''.

http://www.onset.unsw.edu.au/issue2/Contactlenses/Cornea.jpg

http://www.images.missionforvisionusa.org/anatomy/uploaded_images/KnumbMfV-735325.jpg

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Eye03_files/image002.jpg

=====Endothelium of the cornea=====

http://education.vetmed.vt.edu/Curriculum/VM8054/EYE/CRNEADGM.JPG

http://www.hopkinsmedicine.org/bin/n/r/layers_of_cornea.jpg

====Uvea====

http://www.uchospitals.edu/images/nci/CDR0000543553.jpg

=====Choroid of the uvea=====
*The choroid is '''highly pigmented''' and found between the sclera (part of the tunica fibrous) and the retina.
*The choroid has three layers: sclera vasculature, retinal vasculature, and Brunch's membrane.
**The retinal vasculature layer is also called the '''choriocapillary layer'''.
**Bruch's membrane is also sometimes called a ''glassy membrane''.

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSJaMYCunI/AAAAAAAAAvk/jp3rWecT1KU/s800/choroid.jpg

http://neuromedia.neurobio.ucla.edu/campbell/eyeandear/wp_images/175_choroid.gif

=====Ciliary body=====
*Far vision requires a flattened lens (think flat like a frisbee which you hope will go "far") so the ciliary muscle relaxes, the zonules tense, and the lens is pulled into a flatter shape.
*Near vision requires a bulged lens so the ciliary muscle contracts, the zonules relax, and the lens relaxes into a bulge.
*'''Oxytalin''' fibers are used to attach the basement membrane of the non-pigmented epithelium of the ciliary body (part of the uvea) to the basement membrane (called the lens capsule) of the lens.

http://www.unmc.edu/physiology/Mann/pix_7/ciliary.gif

*Ciliary processes:
***Aqueous solution has little protein, some glucose, and similar ion concentration as plasma.
***The pigmented layer (deep layer) of the ciliary process is continuous with the pigmented layer of the retina.
***The non-pigmented layer's (secretory, surface layer) apical surface faces the pigmented layer and the basolateral surface has lots of folds and borders the posterior chamber.
**We call the space between the pigmented and non-pigmented cells the '''ciliary channel''' and consider it a ''potential space''.
**'''Blood-aqueous barrier''': '''occluding junctions''' at the apex of the ciliary process's surface epithelium keeps blood and aqueous solution from mixing.

https://lh6.googleusercontent.com/_WdFQawAlzZM/TaSMDAw19oI/AAAAAAAAAv0/3JVlhulvX9I/s800/ciliary_body_diagram.jpg

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSJyetXfmI/AAAAAAAAAvs/-0q6gDNzx3M/s800/ciliary_body.jpg

http://www.kumc.edu/instruction/medicine/anatomy/histoweb/eye_ear/small/Eye006s.JPG

http://www.images.missionforvisionusa.org/anatomy/uploaded_images/lenszonulegrosscopy2-745514.jpg

http://www.unmc.edu/physiology/Mann/pix_7/ciliary.gif

http://a248.e.akamai.net/7/248/430/20080327144040/www.mercksource.com/ppdocs/us/common/dorlands/dorland/images/zonula_z.%20ciliaris(1).jpg

=====Iris=====
**Note that the posterior epithelium is one and the same as the myoepithelium: it has muscle fibers in it and is responsible for '''dilating''' the pupil.

*'''The malanocytes of the stroma determine eye color.'''
*The stroma is responsible for '''constricting''' the pupil.

*Note that '''dilation is sympathetic''' and '''contraction is parasympathetic'''.

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSpFlJEapI/AAAAAAAAAwI/SRnGaDvroPU/s800/pigmented_myoepithelium.jpg

=====Eye color=====
**http://farm4.static.flickr.com/3093/3196152077_f205a4c2f2.jpg

====Lens====
*The epithelium on the anterior side of the lens is '''simple cuboidal'''.
*Note that '''the lens epithelium does not have occluding junctions'''.

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSrrG6wx6I/AAAAAAAAAwM/KRh5L-hAn_k/s800/lens_cells.png

*In the case of cataracts, lens fibers (the cells that span ant-post and have crystallin) turn opaque and refract light poorly.
*In the case of '''presbyopia''', the lens loses elasticity (some loss is normal during aging) such that the pt cannot ''accomadate'' well and thus has '''poor near vision'''.

====Retina====

=====Pigmented epithelium of the Retina=====
*The pigmented epithelium of the retina is '''simple cuboidal''' and is adjacent to the inner-most layer of the uvea (Bruch's membrane).
**Note that secretion is enabled via '''Na-K ATPase'''.
**concentrates ''and estrifies'' vitamin A for easy reproduction of rhodopsin by rods

=====Neural retina=====

http://upload.wikimedia.org/wikipedia/en/b/bb/Rod%26Cone.jpg

http://www.medgadget.com/archives/img/retinal_layers.jpg

*Rods versus cones
**Rods use rhodopsin while cones have three distinct pigments for three colors: red, green, and blue.

{|border="1"
|-
!Attribute
!Rods
!Cones
|-
|Function
|Night vision (scotopic), low acquity
|Day vision (photopic), color, high acquity
|-
|Photopigment
|Rhodopsin
|3 pigments, 3 wavelength specificities
|-
|Distribution
|"Peripheral"
|"Central"
|-
|Population count
|120 million
|6 million
|}

https://lh4.googleusercontent.com/_WdFQawAlzZM/TaSy4rD93wI/AAAAAAAAAwQ/bgroeQF5CBY/s800/retina.png

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSJyetXfmI/AAAAAAAAAvs/-0q6gDNzx3M/s800/ciliary_body.jpg

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSzKsKAgYI/AAAAAAAAAwY/n4kWukRfoD8/s800/fovea.jpg

Eye

134.68.138.106 — Tue, 12 Apr 2011 17:47:31 GMT

149.166.24.214: /* Lens */

*started here on 04/11/11.

*NBME:
**1/4 of the 100 questions are images.
**No questions on the eye or ear.

==The eye==

===Optical anatomy===
*Important anatomical features of the eyeball include:
**cornea with limbus (outer rim that holds stem cells)
**anterior chamber
**pupil
**iris
**posterior chamber
**ciliary body
**lens (with ciliary processes and zonules)
**vitreous body
**retina
**ora serrata
**fovea
**optical disc

http://www.odec.ca/projects/2006/thog6n2/images/eye_2.gif

===Wall of the eye===
*The wall of the eye is comprised of three layers: fibrous tunic, uvea, retina (where the retina is the inner-most layer).

*The fibrous tunic generates the cornea, the sclera, and provides continuity with the conjunctiva.
**The conjunctiva is a clear mucous membrane that lines the exterior of the sclera and cornea and is continuous along the poster aspect of the eyelid.

*The uvea is the vascular tunic ('''tunica vasculosa''') that carries the vasculature of the eye.
**The uvea also makes the '''iris''', '''ciliary bodies''', and the '''choroid'''.
**The choroid is ''highly vascularized''.

*The retina provides the sensory material of the eye.
**The retina includes the '''pigmented epithelium''', the '''neural photoreceptor cells''', and the '''neuronal integreative circuitry''' and supporting cells.
**Recall that photoreceptor cells come in rods and cones.
**Note that the '''pigmented epithelium is deep to the photoreceptors'''.

https://lh6.googleusercontent.com/_WdFQawAlzZM/TaR2ollnmXI/AAAAAAAAAvc/Ql2QplUuCDY/s800/eyeball_layers.jpg

===Eyeball function by component===

http://www.cytochemistry.net/microanatomy/eye/retina4.jpg

====Cornea====
*The cornea is the most superficial layer of the eye and is exposed to the environment.
**Recall that '''the cornea arises from the fibrous tunic''' of the optical tissue.
*The cornea is '''transparent''', '''avascular''', and bends the incoming light to hit the lens.
**In fact the cornea bends the light (refracts) even more than the lens.
**'''Photorefractive keratectomy''' and '''LASIK''' (laser ''in situ'' keratomileusis) are two surgeries that reshape the deeper (non-epithelial) layers of the cornea to correct poor refraction that results in poor vision.
*The cornea has '''three cellular layers''' and '''two atypical basement membranes'''.
**The layers (superficial to deep): epidermis, Bowman's membrane, stroma, Descemet's membrane, and endothelium.
*'''With age, Descemet's membrane''' decreases in transparency and leads to '''decreased light transmission'''.

http://www.ophthobook.com/wp-content/uploads/2007/12/video-cornealayers.jpg

http://www.lasik.md/img/learnAboutLasik/cornea.gif

http://www.uniteforsight.org/course/image/cornea.jpg

http://thalamus.wustl.edu/course/eye2.gif

=====Epithelium of the cornea=====
*The epithelium of the cornea is made of '''stratified, squamous, non-keratinized epithelium'''.
*The epithelium layer is '''highly proliferative''' and has '''abundant pain fibers'''.
**The epithelial layer maintains a population of stem cells in the limbus area (the junction of the cornea with the sclera).
**Note that aqueous humor (from the anterior chamber) drains through the ''corneoscleral junction (the limbus).
**We call the corneoslceral junction (the limbus) a '''trabecular meshwork''' and the site of '''Schlemm's canal'''.

http://www.dartmouth.edu/~rpsmith/lens.gif

http://www.bu.edu/histology/i/08006loa.jpg

http://library.thinkquest.org/28030/media/schlemm5.gif

http://1.bp.blogspot.com/_kaQ5P19FVgk/THl4ddhkNnI/AAAAAAAAG20/PtY3YVnIgpE/s400/Canal_de_Schlemm.JPG

=====Stroma of the cornea=====
*The stroma is also called the '''substantia propria'''.
**There are '''50-60 layers''' of cells making the stroma the most '''substr
*The stroma is series of layers of '''fibrocytes, proteoglycans, and ECM fibers''' with alternately oriented collagen fibers.
**Note that '''collagen of the stroma is of type 1 and 5''' and are '''non-fibrillar'''.

http://www.onset.unsw.edu.au/issue2/Contactlenses/Cornea.jpg

http://www.images.missionforvisionusa.org/anatomy/uploaded_images/KnumbMfV-735325.jpg

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Eye03_files/image002.jpg

=====Endothelium of the cornea=====
*The endothelium of the cornea contains '''leaky intercellular junctions''' that allow '''exchange of fluid with the anterior chamber'''.
**Drainage by the endothelium '''keeps the stroma relatively dry'''.
*Note that '''fluid transport by the endothelium contributes to the transparency''' of the cornea.

http://education.vetmed.vt.edu/Curriculum/VM8054/EYE/CRNEADGM.JPG

http://www.hopkinsmedicine.org/bin/n/r/layers_of_cornea.jpg

====Uvea====
*Recall that the uvea is one of the three layers of the eye: the tunica fibrous, the uvea, and the retina.
*Recall that the uvea is also called the tunica vasculosa and carriers the vasculature of the eye.
*The uvea includes the iris, the ciliary bodies, and the choroid.
**Just as the cornea is the anterior portion of the fibrous tunic and is completed posteriorly by the sclera, '''the iris and ciliary body are the anterior aspect of the tunica vasculosa''' and are '''completed posteriorly by the choroid'''.

http://www.uchospitals.edu/images/nci/CDR0000543553.jpg

=====Choroid of the uvea=====
*Recall that the choroid is the posterio-lateral aspect of the uvea (tunica vasculosa).
*The choroid carries vasculature to the retina and the sclera.
*The choroid is '''highly pigmented''' and found between the sclera (part of the tunica fibrous) and the retina.
*The choroid has three layers: sclera vasculature, retinal vasculature, and Brunch's membrane.
**The retinal vasculature layer is also called the '''choriocapillary layer'''.
**Note that ''these layers are indistinguishable in the lab''.
**The choriod layer is separated from the retina by the '''Bruch's membrane'''; that is, Brunch's membrane is the deepest aspect of the choroid part of the tunic vasculosa (uvea).
**Bruch's membrane is also sometimes called a ''glassy membrane''.

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSJaMYCunI/AAAAAAAAAvk/jp3rWecT1KU/s800/choroid.jpg

http://neuromedia.neurobio.ucla.edu/campbell/eyeandear/wp_images/175_choroid.gif

=====Ciliary body=====
*The ciliary body is a '''thickening of the vascular layer''' near the anterior aspect, radially from the lens.
*Ciliary bodies have two structures: ciliary zonules (ligaments) and ciliary processes.

*Ciliary zonules (suspensory ligaments):
**Ciliary ligaments project '''from the tunica vasculosa to the lens capsule''' and control the flattness / bulging of the lens in order to focus light (a process called '''accomodation'''.
**Upon contraction of the ciliary muscle, the many ciliary zonules are brought closer together and anterior which actually allows the lens to relax.
***'''Think of the ciliary muscle as a sphincter''' and the relationship with zonules and the lens makes sense.
***Far vision requires a flattened lens (think flat like a frisbee which you hope will go "far") so the ciliary muscle relaxes, the zonules tense, and the lens is pulled into a flatter shape.
***Near vision requires a bulged lens so the ciliary muscle contracts, the zonules relax, and the lens relaxes into a bulge.
***Recall too that '''near vision gives eye strain''' which is the excessive contraction of the ciliary muscles.
**'''Oxytalin''' fibers are used to attach the basement membrane of the non-pigmented epithelium of the ciliary body (part of the uvea) to the basement membrane (called the lens capsule) of the lens.

http://www.unmc.edu/physiology/Mann/pix_7/ciliary.gif

*Ciliary processes:
**Ciliary processes primarily function to '''generate aqueous solution'''.
***Aqueous solution provides '''nutrition to the lens''' and '''maintains intraocular pressure'''.
***Aqueous solution has little protein, some glucose, and similar ion concentration as plasma.
**Ciliary processes are '''an extension of the tunica vasculosa''' (the uvea) and are highly vascularized.
**There are two layers to the ciliary process tissue: deep layer (pigmented) and surface layer (secretory, non-pigmented).
***The pigmented layer (deep layer) of the ciliary process is continuous with the pigmented layer of the retina.
***The non-pigmented layer's (secretory, surface layer) apical surface faces the pigmented layer and the basolateral surface has lots of folds and borders the posterior chamber.
**We call the space between the pigmented and non-pigmented cells the '''ciliary channel''' and consider it a ''potential space''.
**'''Blood-aqueous barrier''': '''occluding junctions''' at the apex of the ciliary process's surface epithelium keeps blood and aqueous solution from mixing.
**Note that '''glaucoma results from blocked drainage of aqueous fluid''' and the resulting elevation of '''intraoccular pressure'''.

https://lh6.googleusercontent.com/_WdFQawAlzZM/TaSMDAw19oI/AAAAAAAAAv0/3JVlhulvX9I/s800/ciliary_body_diagram.jpg

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSJyetXfmI/AAAAAAAAAvs/-0q6gDNzx3M/s800/ciliary_body.jpg

http://www.kumc.edu/instruction/medicine/anatomy/histoweb/eye_ear/small/Eye006s.JPG

http://www.images.missionforvisionusa.org/anatomy/uploaded_images/lenszonulegrosscopy2-745514.jpg

http://www.unmc.edu/physiology/Mann/pix_7/ciliary.gif

http://a248.e.akamai.net/7/248/430/20080327144040/www.mercksource.com/ppdocs/us/common/dorlands/dorland/images/zonula_z.%20ciliaris(1).jpg

=====Iris=====
*The iris the most anterior aspect of the uvea (the vascular layer).
**Recall that the uvea is the middle layer of the three layers of the eyeball: tunica fibrous, tunica vasulosa (uvea), and the retina.
*The iris divides the eyeball into two chambers: the anterior and posterior chambers.
*The iris's job is to regulate the amount of light entering the eye ball.

*The posterior aspect of the iris has epithelial and myoepithelial layers that provide the pigment of eye color and the movement of the iris, respectively.
**Note that the posterior epithelium is highly pigmented but does not determine eye color.
**Note that the posterior epithelium is one and the same as the myoepithelium: it has muscle fibers in it and is responsible for '''dilating''' the pupil.

*The iris is primarily composed of stroma with an '''epithelial covering only on the posterior surface'''.
**The stroma is highly vascular (recall that the iris is part of the tunica vasculosa) and has fibroblasts, connective tissue, melanocytes, and myocytes.
**'''The malanocytes of the stroma determine eye color.'''
**The stroma is responsible for '''constricting''' the pupil.

*Note that '''the stroma contains the constrictor muscle''' of the pupil and '''the myoepithelium contains the dilator muscle''' of the pupil.
**Note that '''dilation is sympathetic''' and '''contraction is parasympathetic'''.

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSpFlJEapI/AAAAAAAAAwI/SRnGaDvroPU/s800/pigmented_myoepithelium.jpg

=====Eye color=====
*Eye color is determined by the '''quantity and distribution''' of pigment cells in the stroma and posterior epithelilum of the iris.
*Pink: complete lack of pigment; albinism (lack of tyrosinase or a defect in melanosome transport, RAf27a)
*Blue < grey / green < brown => less to more pigment.
*Heterochromia iridium is the presence of distinct regions of different color in the iris.
**http://farm4.static.flickr.com/3093/3196152077_f205a4c2f2.jpg

====Lens====
*The lens of the eye is '''biconcave''', '''transparent''', and '''avascular'''.
*The '''lens capsule is the basement membrane''' of the lens and sits on the outer surface.
**Note that the capsule is composed of both lens fiber cells '''and''' epithelial cells.
*The lens has an epithelium but '''only on the anterior surface''' just as the iris only has an epithelium but only on the posterior surface.
**The epithelium on the anterior side of the lens is '''simple cuboidal'''.
**Note that '''the lens epithelium does not have occluding junctions'''.
*The stroma of the lens is composed of highly specialized cells (called '''lens fibers''') that span the anterior-posterior axis and refract light well because of their '''high concentration of crystallin''' a cellular protein.
**The cells at the center of the lens contain the highest concentration of crystallin.
**These stromal cells are 7-10 mm in length.

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSrrG6wx6I/AAAAAAAAAwM/KRh5L-hAn_k/s800/lens_cells.png

*In the case of cataracts, lens fibers (the cells that span ant-post and have crystallin) turn opaque and refract light poorly.
*In the case of '''presbyopia''', the lens loses elasticity (some loss is normal during aging) such that the pt cannot ''accomadate'' well and thus has '''poor near vision'''.

====Retina====
*The retina is the inner-most of the three layers of the eye (tunic fibrous, tunica vasculosa, and retina).
*The retina has two functional layers: the pigmented epithelium on the outside (next to Brunch's membrane from the tunic vasculosa = uvea) and the neural retina.
**Note that the neural retina and the pigmented epithelium are not well connected and thus '''retinal detachment''' often occurs between these two layers.
*The epithelium is essentially a support tissue for the neural retina.
*The unlike the tunica fibrous and (almost) the tunica vasculosa, the retina does not continue all the way anteriorly.
**The anterior apex of the retina is called the '''ora serrata'''.

=====Pigmented epithelium of the Retina=====
*The pigmented epithelium of the retina is '''simple cuboidal''' and is adjacent to the inner-most layer of the uvea (Bruch's membrane).
**Recall that Bruch's membrane is also sometimes called a ''glassy membrane''.
*The pigmented epithelium serves to support the neural retina (which is deeper) and thus its ''apical membrane faces the neural retina'':
**secretes nutrient-rich fluid onto the nueral retina
***Note that secretion is enabled via '''Na-K ATPase'''.
**produces melanin to absorb light and reduce scatter
**cleans up material shed by rods an cones (phagocytosis, discs)
**concentrates ''and estrifies'' vitamin A for easy reproduction of rhodopsin by rods

=====Neural retina=====
*The neural retina is the inside (deep) layer of the retina's two layers (pigmented epithelium and neural retina).
*The cells that make up the neural retina include: photoreceptors (rods and cones), supporting cells, and integrative neurons.

*Rods and cones have their own anatomy related to their function (from closest to the field of view to closest to the brain): synaptic body, inner segment, outer segment.
**The synaptic body is in contact with bipolar cells of the retina.
***Note that the location of synapse from the photoreceptor to the bipolar cell is ''closer to the field of view than the location of photoreception''.
**The inner segment:
**The outer segment contains the photosensitive apparatus, has highly modified cilium, and is in contact with the pigmented epithelium.
***Note that '''the outer segment is closes to the brain'''.

http://upload.wikimedia.org/wikipedia/en/b/bb/Rod%26Cone.jpg

http://www.medgadget.com/archives/img/retinal_layers.jpg

*Rods versus cones
**Rods are specialized for low light vision while cones are specialized for high light and color vision.
***"C" is for color.
**Rods use rhodopsin while cones have three distinct pigments for three colors: red, green, and blue.
**Rods are associated with the "peripheral" areas of the eye while the cones are found in higher density at the "center" region.
***Note that "peripheral" and "central" are quoted because we don't really mean the "center" we mean near the '''fovea centralis'''--the focal point of highest acuity.
***It makes sense that the cones are concentrated in the "central" area because they are high acquity photoreceptors and the center is where our focal point usually sits.
**The '''fovea''' is the cones-only area of the retina and the location of '''highest visual acquity'''.

{|border="1"
|-
!Attribute
!Rods
!Cones
|-
|Function
|Night vision (scotopic), low acquity
|Day vision (photopic), color, high acquity
|-
|Photopigment
|Rhodopsin
|3 pigments, 3 wavelength specificities
|-
|Distribution
|"Peripheral"
|"Central"
|-
|Population count
|120 million
|6 million
|}

https://lh4.googleusercontent.com/_WdFQawAlzZM/TaSy4rD93wI/AAAAAAAAAwQ/bgroeQF5CBY/s800/retina.png

https://lh5.googleusercontent.com/_WdFQawAlzZM/TaSJyetXfmI/AAAAAAAAAvs/-0q6gDNzx3M/s800/ciliary_body.jpg

https://lh3.googleusercontent.com/_WdFQawAlzZM/TaSzKsKAgYI/AAAAAAAAAwY/n4kWukRfoD8/s800/fovea.jpg

==Lab==
*Note that the Bowman's membrane in the cornea is large and thick and separates the stroma from the epithelium.

*stopped here on 04/11/11.

Skin

134.68.138.106 — Tue, 12 Apr 2011 14:50:36 GMT

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tIiQRZ wow, awesome blog.Really thank you! Awesome.

Female reproductive

149.166.24.228 — Mon, 11 Apr 2011 17:54:20 GMT

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Endocrine

149.166.24.243 — Thu, 07 Apr 2011 00:55:03 GMT

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Male reproductive

149.166.24.65 — Wed, 06 Apr 2011 15:09:30 GMT

149.166.24.214: /* Segments of the male reproductive tract */

*started here on 04/06/11.

*State wide exam:
**Previously the NBME exam had nothing to do with our histo course; there was lots of CMB, etc.
**So now they make a customized NBME.
**100 questions
**2.5 hours (150 minutes)
**'''Does not cover special senses'''.
**We are the last of the centers to take the NBME exam.
**How to study: use the high-yield materials; some have not studied and done just fine.
**Review session on Wednesday before the exam.

==Male reproductive==

===Anatomy review===
*The testes are egg-shaped organs covered with a '''cartilagenous capsule called the tunica albuginea'''.
*The testes are divided into lobules; '''lobule division is incomplete and achieved by the connective tissue septae'''.
**There are approximately 250 lobules in the testis.
**'''Each lobule has one or several seminiferous tubules'''.
*The '''mediastinum testis''' is where the vessels (blood and lymphatics), nerves, and efferent duct enter and exit the testis.
**The mediastinum testis lies at the posterior aspect of the testis.
**Note that the mediastinum testis is connective tissue while rete testis is a collecting tubule tissue.
*Seminiferous tubules are '''blind ended, highly coiled, and lined with spermatic epithelium'''.
**It is within the seminiferous tubules that spermatogenesis takes lace.
**The '''tunica propria''' is the outer wall of the seminiferous tubule and is made of '''smooth muscle and fibroblasts'''.

===Seminiferous epithelium===
*The seminiferous epithelium (the inside of the seminiferous tubule, recall) is a '''stratified''' epithelium and is responsible for generating male gametes.
*There are multiple types of '''spermatogonia''' in the seminiferous epithelium: type A and type B.
*Type A spermatogonia are stem cells.
*Type B spermatogonia are highly mitotic progenitor cells.
**Type B spermatogonia are connected via '''cytoplasmic bridges which help synchronize maturation''' of developing spermatozoa.
*Note that ''we will not differentiate between type A spermatogonia and type B spermatogonia in lab''.
*Spermatids remain in close physical contact with the Sertoli cells throughout development.

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection3/TestesandSperm03_files/image002.jpg

===Spermatogenesis===
*Recall the order cell names in spermatogenesis: type A spermato'''gonia''' -> type B spermato'''gonia''' -> primary spermato'''cyte''' -> secondary spermato'''cyte''' -> sperma'''tid''' -> spermato'''zoa'''.
**Primary spermatocytes are in the prophase of meiosis 1 and stick around for 20 days.
**Secondary spermatocytes are relatively short-lived.
**Note that spermatids shed their ''residual bodies'' as they become spermatozoa.
*Recall the order of divisions in spermatogenesis: mitosis, mitosis / differentiation, meiosis 1, meiosis 2, differentiation.
**Note that mitosis from type A spermatogonia to type B spermatogonia will maintain the stem cell population and will occur more than once such that many type B spermatogonia are generated.

*As spermatogonia develop, they move from the '''basal compartment''' to the '''adlumenal compartment'''.
**We call this adlumenal movement.
**Cells of the basal compartment: type A and type B spermatogonia, primary spermato'''cytes'''
**Cells of the adlumenal compartment: secondary spermatocytes, spermatids, spermatozoa

*Cells and processes: type A spermatogonia undergo mitosis to become ... type B spermatogonia undergo mitosis (and differentiation) to become ... primary spermatocytes undergo meiosis 1 ... secondary spermatocytes undergo meiosis 2 ... spermatids undergo morphologic modification (differentiation) ... spermatozoa.
**'''Spermatocytogenesis''' includes all the steps that generate an increasing number of cells (that is, type A spermatogonia through generation of secondary spermatocytes); this makes sense because of the name "cyto" = cell and genesis = "origin of".
**'''Spermiogenesis''' is the converse of spermatocytogenesis: spermeiogenesis is the maturation of existing cells into spermatozoa (from the secondary spermatocyte stage to the spermatozoa stage).

*It takes 60-70 days for spermatogonia to progress to spermatozoa.

http://image.wistatutor.com/content/reproduction-in-animals/spermatogenesis-and-spermiogenesis-stages.jpeg

http://image.wistatutor.com/content/reproduction-in-animals/spermatogenesis-spermiogenesis-process.jpeg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab27/IMAGES/MREPL08.JPG

====Mitosis and Meiosis====
*Recall that mitosis occurs when one 2N (diploid, like most cells of the body) cell makes a copy of the chromosomes (making it temporarily 4N--tetraploid) and divides the two copies up between two cells; both daughter cells are 2N.
*Recall that meiosis occurs when one 2N (diploid) cell makes a copy of the chromsosomes (making it temporarily 4N--tetraploid) and divides the two copies up between two cells--twice; all four daughter cells are 1N (haploid).
*So, primarly spermatocytes are the initial cell, secondary spermatocytes are the first generation of meiosis daughters, and spermatids are the second generation of meiosis daughters.
**That is, secondary spermatocytes are the result of meiosis 1 (2N->4N->2N) and spermatids are the result of meiosis 2 (2N->1N).

====Spermiogenesis====
*Recall that spermiogenesis occurs on existing cells (spermatids) and does not generate any new cells.
*Spermiogenesis is characterized by morphological changes to the spermatid, that is the specialization / differentiation of the spermatid into the spermatozoa:
**Loss of cytoplasm
**Condensation of genetic material and nucleus
**Formation of the acrosome
**Formation of the axoneme
*Spermiogenesis has '''3 phases: golgi phase, acrosomal phase, maturation phase'''.'
**''We will not be asked to identify the phase of a developing spermatid.''

*Golgi phase:
**The golgi phase generates the ''polarization of the cell''; it is called the ''golgi phase'' because the '''golgi becomes the acrosome'''.
**The enzymes like hyaluronidase and trypsin-like protease accumulate at one pole of the nucleus in a vesicle (which will become the acrosome).
***This makes sense because upon greeting an oocyte, the spermatozoa will use the enzymes within the acrosome to digest away the shell of the oocyte so it can fertilize.
**The centrioles (which will become the axoneme) migrates to the opposite pole as the enzyme vesicle.

*Acrosomal phase:
**The acrosomal phase is characterized by ... the development of the acrosome.
**The vesicle of enzymes flattens out over one pole of the nucleus.
**The cell '''rotates such that the axoneme faces the lumen'''.

*Maturation phase:
**The maturation phase is characterized by motile apparatus development and the capacity to fertilize.
**The cell body is shed, generating the '''residual body'''; upon shedding, the sperm are released into the lumen of the seminiferous tubule.
***Note that the sertoli cells clean up the residual bodies.
**Note that '''during the maturation phase, the spermatids are not yet motile or fertile'''.
***Though they may wiggle a little bit.

*Note that we can distinguish four parts of the spermatazoa: head, middle, principle piece, and end piece.
**The Head contains the nucleus and acrosome.
**The middle piece contains the mitochondria.
**The principle piece is primarily axoneme.
**The end piece is only the very last portion of the axoneme.
http://www.ccs.k12.in.us/chsBS/kons/kons/images/spermiogenesis.jpg

===Sertoli cells===
*Recall that Sertoli cells function as supporting cells for germ cells that generate spermatozoa.
**'''Sertoli cells condition the microenvironment for gamete production'''.
**Recall that Sertoli cells are physically close to the developing gametes.
*'''Sertoli cells are a tall, columnar epithelial cell'''.
*Sertoli cells are characterized by being '''tall, columnar''' epithelial cells with a '''large, indented euchromatic nucleus''', and lots of eosinophilic cytoplasm.
*Neighboring Sertoli cells within a region have '''gap junctions which suggest that Sertoli cells are coordinated within their region'''.
**Coordination through gap junctions would explain the fact that different regions of the seminiferous epithelium (which includes sertoli cells and spermatogonium) are at different stages of spermatid development. (That is, while one place may have a batch of spermatids going through morphological changes to be come spermatozoa, the neighboring region could have a group of primary spermatocytes undergoing meiosis 1 to generate secondary spermatocytes.)
**Recall that it takes about 70 days for a spermatogonium to generate spermatozoa.

*stopped at minute 31.

====Blood testis barrier====
*It is important that the developing spermatozoa be kept separate from the blood supply because antibodies native to the pt can attack the developing spermatozoa because of immunologically active proteins generated through chromosomal recombination of meiosis 1.
**The capillaries of the testes are '''fenestrated'''; such a capillary provides little to know barrier against antibodies.
*Sertoli cells of the seminiferous epithelium form tight junctions between one another to keep immunoglobulins in the blood from entering the lumen of the tubule.
**Note that these '''tight junctions of the Sertoli cells are on the ''lumenal'' side of the spermatogonia'''.
**These tight junctions define the two compartments: basal compartment and adlumenal compartment.
*Recall that spermatogonia through the primary spermatocytes are in the basal compartment and secondary spermatogonia through spermatozoa are in the adlumenal compartment.

*Occasionally, cells that should reside in the adlumenal compartment and be separate from immunological agents are detected and the ensuing immunological response results in infertility.

====Sertoli function stimulated by FSH====
*Recall that the anterior pituitary releases FSH which binds to the FSH receptor on Sertoli cells.
**For related recall, LH is released by the anterior pituitary to bind on LH receptors of the Leydig cells found in the interstitium between the seminiferous tubules.
*FSH signaling on Sertoli cells causes phagocytic activity and production of several secretions.
*Secretions of the Sertoli cells:
**Activin and Inhibin: stimulate and inhibit the anterior pituitary cells to release FSH.
**Androgen binding protein (ABP): secreted into the lumen of the seminiferous tubule, binds up and concentrates testosterone.
**Tubular fluid: lubrication.
*Phagocytic activity of Sertoli cells is responsible for degrading residual bodies and malformed spermatozoa.

===Leydig cells===
*Leydig cells produce testosterone upon signaling from the anterior pituitary via LH.
**Recall that testosterone negatively feeds back on the hypothalamus.
**Note that '''Leydig cells do not secrete activin or inhibin'''.
*Leydig cells are found in clusters in the '''peritubular interstitium''' of the testis, between the seminiferous tubules.
**Recall that Leydig cells are often found near capillaries.
*Leydig cells are characterized by eiosinophilicism, lots of sER, mt with tubular cristae, and '''a lack of secretory vesicles'''.
**Regarding lots of sER, recall that steroids are generated in sER.
**Regarding a lack of secretory vesicles recall that steroids can pass directly through the membrane and therefore need not vesicular secretion.
**By transmission EM, one can also discern '''crystalline inclusions'''.

*Leydig cells are "transiently" active during development and then initiate full activity at puberty.

*Recall that Sertoli cells generate ABP (androgen binding protein) upon FSH signaling and Leydig cells produce testosterone upon LH signaling.
*It is by the parallel production of ABP and test (by Sertoli and Leydig cells) that testosterone is effectively delivered to the male reproductive tract.

===Segments of the male reproductive tract===
*The male reproductive tract begins at the seminiferous tubules and runs to the penile urethra.
*Seminiferous tubules -> tubuli recti (straight tubules) -> rete testis -> efferent ductules -> epididymal ducts -> ductus deferens (vas deferens) -> ejaculatory duct -> prostatic uretral -> membraneous urethra -> penile urethra.
**The seminiferous tubules reside in the lobules of the testis.
**The seminiferous tubule runs posteriorly and medially (toward the mediastinum) to the rete testis via the tubuli recti.
**The rete testis are a collecting system of the tubuli recti that dump into the efferent ductules.
**Efferent ductules (recall that the "e" of efferent means exiting) allow exit of the fluid to the epididymal duct (e-duct -> e-duct).
**The epididymal duct leads to the organ called the epididymis, which lies on the posterior, caudal aspect of the testis.
**Fluid travels from the epididymis superiorly via the ductus deferents.
**The tract becomes the ejaculatory duct once the seminal vesicle has joined; this makes sense if you think "now that we have seminal secretions (60% of the fluid) we're getting ready for ejaculation).
**The rest of the tract is the urethra and then named based on the structure through which the tract is laid: the prostate, then the membranous part of the penis, and then penis proper.

Where do basal cells and principal cells start?

*Straight tubule (tubuli recti)
**As the name implies, these are relatively straight tubules.
**Contributes to fluid
**Cuboidal to columnar
**'''Contains the highest density of Sertoli cells'''

*Rete testis
**This is an elaborate network of channels.
**Contributues to fluid
**Has an '''irregular epithelial morphology''': squamous, cuboidal, columnar.
**Has a '''fibrous stroma'''

*Efferent ductule
**The efferent duct connects the rete testis to the epidiymal duct and really does "exit" the testis proper and pass through connective tissue like the tunics.
**Like the rete testis, the efferent ductule has an irregular epithelial morphology and also has '''ciliated, pseudostratified cells'''.
***These ciliated pseudostratified cells are called '''principal cells''' and are found as clusters of columnar cells surrounded by short cells.
***These cells are the only ciliated cells of the male genital tract; it even makes a bit of sense that these are ciliated because they are passing through a sturdy connective tissue structure.
**The short cells that surround the columnar cells are absorptive cells.

*Ductus epididymis
**Leads to the organ called the epididymis.
**The ductus epididymis is characterized by an pseudostratifed columnar epithelium, '''stereocilia''', and a '''prominent muscularis layer'''.
**The ductus epidiymis is pseudostratified epithelium (like the efferent ductule) and has '''stereocilia''' (which are different than cilia!).
***Note that stereocilia are not like cilia because they don't move and they are not like microvilli because they are not that small.
**The ductus epididymis is characterized by '''basal cells and principle cells'''.
***'''Basal cells are regenerative.'''
***'''Principal cells are secretory / absorptive.'''
**The ductus epididymis has a prominent muscularis layer that thickens distally and changes from just a circular layer to an '''inner circular and outer longitudinal layer'''.
**The functions of the ductus epididymis: absorb 90% of the tubular fluid, secrete factors that mature and capacitate sperm, and phagocytize cellular debris.

*Ductus deferens (vas deferens)
**The ductus deferens is characterized by a pseudostratified columnar epithelium, '''abundant sympathetic innervation''', and '''three layers to the muscularis'''.
**The ductus deferens is pseudostratified (like the efferent ductule and ductus epididymis) and has stereocilia (like the ductus epididymis).
**The muscularis has now added an inner longitudinal muscle layer to the ductus epididymis's inner circular and outer longitudinal.
**The sympathetic innervation will be important for ejaculation which is facilitated by contraction of the ductus deferens's muscularis.
***Recall that Point and Shooting require Parasympathetic and Sympathetic innervation.
**The ductus deferens runs '''within the spermatic cord'''.

*Ejaculatory duct
**The ejaculatory duct begins where the vas deferens (ductus deferens) joins the seminal vesicle.
**Bilateral ejacualtory ducts (one from each testis) enter the prostate.

*Membranous urethra
**The membranous urethra is characterized by a '''pseudostratified epithelium that transitions to a stratified columnar epithelium.'''
**The membranous urethra crosses the muscular UG diaphragm.

*Penile urethra
**The penile urethra is characterized by a '''pseudostratified epithelium that transitions to a stratified columnar epithelium''', perhaps continuing on to '''stratified squamous epithelium at the top'''.
**The penile urethra is also characterized by the presence of '''urethral glands''' which are clusters of mucus cells in the mucosa.

{| border="1"
|-
! Section
! Epithelium
! Appendages
! Muscularis
|-
| Seminiferous tubule
| stratified
| none
| none
|-
| Tubuli recti
| cuboidal -> columnar
| none
| none
|-
| Rete testis
| irregular: squamous, cuboidal, columnar
| none
| none
|-
| Efferent ductule
| pseudostratified
| cilia
| none
|-
| Ductus epididymis
| pseudostratified
| sterocilia
| circular -> circular (inner) + longitudinal
|-
| Ductus deferens
| pseudostratified columnar
| stereocilia
| longit (inner) + circular + longit
|-
| Ejaculatory duct
| pseudostratified columnar
| ?
| ?
|-
| Prostatic urethra
| pseudostratified -> simple columnar
|
|
|-
| Membranous urethra
| pseudostratified -> stratified columnar
| none
| longit (inner) + circular + longit
|-
| Penile urethra
| pseudostratified -> stratified columnar -> stratified squamous
| none
| longit (inner) + circular + longit
|}

===Accessory glands of the male reproductive tract===

====Seminal vesicles====
*Seminal vesicles (paired bilaterally) are responsible for producing the largest portion of the semen.
*Seminal secretions are rich in fructose (for energy), prostaglandins, amino acids, and ascorbic acid.
**This generates a '''viscous mucoid secretion'''.
*The seminal vesicle has plenty of '''smooth muscle''' with which to force this secretion out into the ejaculatory duct.
*Seminal vesicle function and growth is mediated by testosterone.
*The vesicles are blind-ended pouches near the prostate and ductus deferens.
*'''Seminal vesicles are lined with pseudostratified columnar epithelium'''.
**This makes sense because they pump semen out into the GU tract at the ductus deferens and ejaculatory duct, both of which are pseudostratified.
*The seminal vesicles have '''mucosal arches''' which are highly folded, convoluted walls.

====Prostate====
*The prostate as an organ surrounds the base of the bladder.
*The prostate generates a secretion that becomes part of the semen and '''serves to condition the environment of the famale GU tract'''.
*The '''fribromuscular stroma''' surrounding the prostate is important for proper discharge of prostatic secretions during ejaculation.
*The prostatic secretion is a water, acidic mix of factors like zinc and fibrinolysin.
**Zinc inhibits macrophage activity.
**Fibrinolysin inhibits clot formation in the uterus.
*The prostate as a gland has alveoli connected via tubules; the tubules converge to generate a '''group of ducts''' that dump into the '''urethral crest'''.
**The urethral crest receives the ejaculatory ducts and becomes the prostatic urethra.
**The epithelium within the gland is irregular: pseudostratified to simple columnar.
*'''Corpora amylacea''' is a concentration of glycoprotein-rich secretion in the lumen of the gland that stains eosinophilic (because of the "protein-rich" part).

*The prostate has three concentric-like zones: central zone, transitional zone, and peripheral zone.
*The '''central zone''' of the prostate is the most medial and contains primarily '''periurethral mucosal glands'''.
**The central zone often stains the lightest of the zones.
*The '''transitional zone''' of the prostate is the middle zone and contains '''periurethral submucosal glands'''.
**Note that the '''central and transitional zones''' are most commonly associated with '''benign prostatic hypertrophy (BPH)'''.
*The '''peripheral zone''' of the prostate is the outer zone, contains the '''main glands''', is called the '''prostate proper''', and is commonly involved with '''malignancies'''.
**The peripheral zone is often involved with '''prostate cancer'''.

====Bulbourethral glands====
*The bulbourethral glands produce a secretion for lubricating the male GU tract for ejaculation.
*The secretion of the bulburethral gland is clear and viscous.

===Ejaculation sequence===
*Ejaculation has a particular series of events regarding all these secretions:
**Bulbourethral glands discharge to lubricate.
**Prostate releases contents (via contraction of the fibromuscular stroma).
***Recall that the prostate's secretions serve to condition the female GU tract.
**The ductus deferens receives sympathetic stimulation to contract its muscularis (1->2 layers), thus pushing spermatozoa into the urethra.
**Seminal vesicles discharge their contents thus clearing the urethra by pushing semen distally.

*stopped here on 04/06/11.

==Lab==
*In the seminiferous tubules:
**Spermatogonia are right on the BM.
**Primary spermatocytes are light staining with dense chromosomes just adlumenal to the spermatogonia.
**We won't have to ID secondary spermatocytes.
**Spermatids are '''round cells''' with dense nucleus.
**Spermatozoa are '''elongated cells''' embedded in Sertoli cells.
**Sertoli cells have '''abundant cytoplasm'''.

*ID straight tubules by the presence of Sertoli cells.
*Ductus epididymis has very tall cells with cilia.
*Ductus deferens ID by stereocilia and three layers of muscle.
*Seminal gland: mucosal arches
*Prostate is ID'd by '''corpora amylacea''' (a concentration of glycoprotein-rich secretion in the lumen of the gland that stains eosinophilic).

Urinary 1 and 2

149.166.25.243 — Mon, 04 Apr 2011 15:23:57 GMT

149.166.24.214:

*started here on 03/21/11.

==Urinary 1==
*The kidney has one of the most complex 3 dimensional organizations of all the organs of the body.
*We will study the kidney incrementally, beginning with the uriniferous tubule.
**We will study some simpler kidneys that contain only one papillary, called "unipapillary kidneys".
*The functional unit of the kidney is the '''uriniferous tubule'''.
**We have 1 million uriniferous tubules.

http://image.wistatutor.com/content/excretion/malpighian-nephron-structure.jpeg

===Cortex and Medulla===
*The kidney has two major regions: the cortex on the outside and the medulla on the inside.
*The pelvis is the sinus area of the kidney that is "sub-medulla" and forms the collecting area for urine before it enters the ureter.
*Urine is produced by '''lobes''' which contain a single '''renal papillum''' which dumps urine into the '''pelvis''' which dumps into the ureter.
**Small mammals often have only one lobe and therefore one renal papillum.
**Humans have multiple lobes and therefore multiple renal papilla.
*In unipapillary kidneys, the uriniferous tubules run all the way from the cortex to the papillum-pelvic border.
*The urine drips off the papilla (papillum) into the pelvis.

http://www.sweethaven02.com/MedTech/AnatPhys/human01_37.jpg

http://iws.collin.edu/mweis/Images/Dissections/pig%20dissections/pig%20dissections%20labeled/pig_kidney_cortex_medulla_calyces_labeled.png

===More on macrostructure===
*Each uriniferous tubule is situated in one of the many medullary rays and medullary pyramids found in humans.
**The cortical region contains the glomeruli and is called the medullary ray.
**The medullary area contains the vasa recta, the loop of Henle, and the collecting duct.
*Medullary pyramids are separated by '''renal columns of Bertin'''.
*The renal pelvis is the area where the ureter begins to form from the sinus of the kidney.

http://www.sci.sdsu.edu/classes/bio100/Lectures/Lect16/Image271.gif

===Uniferous tubule function===
*The uriniferous tubule is made up of epithelial cells.
*The tubule is surrounded by two sets of capillaries:
**The glomerular capillaries are within the Bowman's capsule in the cortex.
**The peritubular capillaries are within the medulla, along the length of the loop of Henle and the collecting duct.
*The '''renal corpuscle''' is the glomerulus, Bowman's capsule, and the glomerular capillaries.
**The renal corpuscle's function is to filter the plasma passing through the glomerular capillaries.
*The '''nephron and collecting''' describes everything other than the renal corpuscle.
**The nephron and collecting duct serve to secrete waste products and reabsorb nutrients to / from the filtrate.

*Note that the kidney filters by throwing out everything and then collecting back the things it wants to keep.
**This is good because the kidney doesn't have to know what needs to be gotten rid of which could be infinite things; the kidney only needs to know what it wants to keep.

http://www.siumed.edu/~dking2/crr/images/RN003b.jpg

===Uriniferous tubule layout and embryonic development===
*Though we draw the uriniferous tubule as a simple, linear tract, it is rarely this simple in final 3D form.
*It is important to understand embryonic development to understand why the uriniferous tubule takes its certain and functional 3D form.
*For proper functioning, it is critical that certain sections of the uriniferous tubule lie next to one another.

*The first form of a plasma filtering mechanism in the developing human embryo is called the '''mesonephric kidneys'''.
*Mesonephric kidneys reach their maximum size at 8 weeks and then undergo a large change.
*Parts of the mesonephric kidneys persist in men to form:
**the efferent ductules,
**the epididymis,
**the ductus deferens, and
**the ejaculatory duct.
*The cloaca is an early developing orifice that serves to excrete feces and urine.
**The cloaca is common between placental mammals, birds, amphibians, etc.
**The cloaca is retained by birds, amphibians, and reptiles.
**The cloaca in mammals divides and conributes to the anus and the urethra / vagina.

*The early plasma filtering structure is divided into two sections: the '''mesonephros''' and the '''metanephros'''.
*'''The metanephros gives rise to the permanent kidneys.'''
**The metanephros contains the '''metanephric mesenchyme''' and the '''uritic bud'''.
**The uritic bud and the metanephric mesenchyme are both composed of epithelial cells.
*The uritic bud grows up into the '''nephrogenic mesoderm''' which is part of the metanephros.

===Uritic bud and nephrogenic mesoderm interaction===
*The uritic bud grows into the nephrogenic mesoderm to form the mature uriniferous tubules.
*The interaction between the uritic bud and the nephrogenic mesoderm is called '''reciprocal induction'''.
**Reciprocal induction: "... tissues causing changes in each other due to signals and receptors in each" per [http://bama.ua.edu/~joshua/archive/nov02/Robin%20Mallard.pdf this paper]
***If the bud doesn't grow up into the nephrogenic mesenchyme, neither tissue becomes what it should.

*As the uritic bud grows into the nephrogenic mesenchyme, the '''uritic bud''' is the primary epithelial cell tubule structure that will become the collecting duct.
**Recall that mesenchymal cells are connective tissue cells.
**Recall that mesenchyme looks like loose connective tissue with lots of spindly, undifferentiated cells within.
*Renal corpuscles develop along the length of the uritic bud (that is, the developing collecting duct) and therefore can originate from the tip of the uritic bud or from epithelium that develops along side the uritic bud.
*Renal corpuscle and nephron development from the tip of the uritic bud:
**At the tops of the uritic bud, mesenchymal cells of the nephrogenic mesenchyme '''condense''' and are induced to make a '''mesenchymal-epithelial transition''' (MET).
***Condensation includes proliferation
**These MET cells will become the epithelial cells of the glomerular capsule.
**The bud tip then expands to develop the PCT (proximal convoluted tuble), loop of Henle (LoH), and the DCT (distal convoluted tubule).
**The MET shifted cells of the early glomeruli recruit the formation of blood vessels that will become the glomerular capillaries.
*Renal corpuscle and nephron development adjacent to the uritic bud
**Along side the uritic bud, epithelial tracts form as '''S-shaped''' or '''comma-shaped''' tubule structures.
**The tops of these se epithelial tracts will become the glomeruli and the length will become the PCT, LoH, and the DCT.

*The s-shaped buds from condensation, proliferation, and MET of mesenchymal cells will form the PCT, LoH, and DCT.

http://herkules.oulu.fi/isbn9514269918/html/graphic11.jpg

http://img.medscape.com/fullsize/migrated/editorial/journalcme/2008/12499/kerecuk.fig1.gif

http://www.sonoworld.com/images/FetusItemImages/article-images/urinary_and_adrenal/prune_belly_syndromes_files/image78.jpg

===Renal corpuscle structure===
*The renal corpuscle demonstrates the unique development of the uriniferous tubule by the way the podocytes surround the glomerular capillaries.
**Note that '''podocytes are a type of epithelial cell'''.
**Capillaries are a type of endothelial cell.
*We call the glomerulus the '''glomerular tuft before fully developed'''.
*Within the capillaries as they develop within the glomerular tuft, there is '''connective tissue holding the capillaries in place'''.
**This connective tissue is called '''mesangium'''.
*'''Bowman's space is the epithelial tract that surrounds the tuft of capillaries.'''
**Bowmans capsule is made of ''simple squamous epithelium''.
**Note that this place forms a complex structure surrounding the many, convoluted, cross-connected capillaries within.

*There are many cell types and structures of the renal corpuscle; each cell type has a specific location and function.
*The afferent arteriole is made of endothelial cells and brings blood to the glomerular capillaries.
*The efferent arteriole is made of endothelial cells and takes blood away from the glomerular capillaries (to the peritubular capillaries).
*The Bowman's capsule is made of epithelial cells and surrounds the glomerular capillaries, forming the '''Bowman's space beween the Bowman's capsule and the walls of the glomerular capillaries'''.
**The inside layer of the Bowmans capsule covers the convoluted capillaries and is called the '''visceral layer'''; the parietal layer is the outside layer that forms the outer barrier of the glomerulus and is continuous with the epithelium of the PCT.
**The visceral bowmans capsule is made up of podocytes.
**The Bowman's space is the location into which filtrate is first formed by being pressed out of the plasma by hydrostatic forces (primarily, but also including colloid osmotic pressures).
**Often there is pink material in the bowmans space; it is brush border from the proximal tubule that has washed backward during fixation.
*The epithelial cells of the Bowman's capsule are continuous with the epithelial cells that make up the proximal convoluted tubule which carries filtrate.
*The distal convoluted tubule (which is, like the PCT, made up of epithelial cells) passes by the afferent arteriole along side the glomerulus.
**The DCT has specialized cells called '''macula densa cells'' on the surface that is closest to the afferent arteriole.
**Macula densa cells release signals PGE2 to cause the afferent arteriole to vasodilate and ATP to cause the afferent arteriole to constrict.
**Macula densa cells are more columnar, stain darker, and have rounder nuclei than the endothelail cells of the DCT.
*Juxtaglomerular cells (also called granular cells) are endothelial cells of the afferent arteriole that contain '''granules of renin'''.
**Granular cells (AKA juxtaglomerular cells) have a large, flattened nucleus, that is more prominent than the nucleus of lacis (extraglomerular mesangial) cells.
**Granular cells release their renin upon PGE2 binding their EP4 receptor.
**Recall that renin will activate angiotensinogen leading to angiotensin 2 and systemic vasodilation.
*Lacis cells (also called extraglomerular mesangial cells) hold the DCT, the afferent arteriole, and the glomerulus together.
**Extraglomerular mesangial cells may also have some functioning in modifying the signals released by the macula densa cells as they travel to the granular / endothelial cells of the afferent arteriole.
**Lacis cells (extraglomerular mesangial cells) are found between the macula densa cells and the afferent arteriole endothelial cells.
**Lacis cells have a lighter stain and less prominent nucleus as compared to granular (juxtaglomerular) cells.
***This makes sense because granular cells will have granules full of the protein renin.
**Extraglomerular mesangial cells are found between the convoluted capillaries, too, and serve to hold the loops in their structure.
***In this case, the mesangial cells are located within the basement membrane.
**Lacis cells can send processes into the lumen of the capillaries between the endothelial cells.

http://sitemaker.umich.edu/ransom.lab/files/glomerulus.jpg

http://www.nature.com/ki/journal/v74/n1/images/ki2008128f4.jpg

http://cmm.ucsd.edu/farquhar/images/Res6_Fig2_EM_Podocyte.gif

http://homepage.smc.edu/wissmann_paul/physnet/anatomynet/anatomy/podocytes2.jpg

http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab23/IMAGES/VASPOLE2%20B.jpg

http://www.kidneypathology.com/Imagenes/Histologia/Histo_AYG_2.jpg

===Forming a filter at the capillary-Bowman-space junction===
*There are three levels of filtration at the capillary-Bowman-space junction.
*The filtrate must first get through the endothelium of the capillary, then through the basement membrane, and then through the feet of podocytes.

*The endothelium of glomerular capillaries is '''fenestrated without diaphragms''' to allow only very small proteins and smaller molecules through.

*The basal lamina does restricts even the smallest proteins.
**There are three layers to the basal lamina (basement membrane) of the glomerulus.
**The three layers are probably only separate in slides as a result of processing, but they are still effective markers for pathology.
**The '''lamina rara extrna''' is farthest from the lumen of the capillary.
**The '''lamina rara interna''' is closest to the lumen of the capillary.
**The '''lamina densa''' is between the ''lamina externa'' and the ''lamina interna''.
**These layers appear as a light-dark-light pattern in EM.

*Podocytes are a type of epithelial cell that provide the finest level of filtration of the plasma as it crosses into the Bowman space.
**Podocytes project feet that sit on the outside (that is, the Bowman space side) of the capillaries.
*Podocytes often interdigitate to provide a nice tight filter.
*Podocytes form '''slit pore diaphragms''' which are very small and let only small molecules through to the bowmans space.

*Water and small molecules pass freely into the Bowman space.
*It is still disputed what factors play the primary role in keeping proteins from entering the filtrate.
**Some say the anionic charge of the basement membrane, which would repel proteins which are generally negatively charged, is the primary factor that hinders protein passage.
**Others point to the podocyte processes and the important proteins that make up the processes (ZO1, nephrin, Neph1) as the primary protein-hindering mechanism.
**Nephrin seems to form a lattice between podocyte processes that would prevent proteins from passing into the bowman space.
http://www.nature.com/ki/journal/v73/n6/images/5002798f1.jpg
**Recall that '''ZO1 is associated with tight junctions'''.

===Mesangial cells===
*Recall that mesangial cells reside between capillaries within the basement membrane.
**Recall that '''basement membranes are always made of type 4 collagen!'''
*Mesangial cells may modulate capillary blood flow.
*Mesangial cells may also act as phagocytes within the basement membrane of the glomerulus.
*Mesangial cells '''reaches out and cups''' each capillary around it.
*Mesangial matrix is made up of collagen, glycans, proteoglycans, etc.

http://www.siumed.edu/~dking2/crr/images/corp5.jpg

http://herkules.oulu.fi/isbn9514264290/html/graphic55.png

http://content.answcdn.com/main/content/img/oxford/Oxford_Body/019852403x.cell.1.jpg

http://www.ndt-educational.org/images/MGP0001.jpg

===The proximal tubule===
*The proximal tubule's primary function is reabsoprtion.
**Approximately 2/3 of the filtrate is reabsorbed in the PT (proximal tubule).
*The proximal tubule is characterized by being large, being eosinophilic (cuboidal, continuous, uniform), and having central nuclei.
**Eosinophilic means the cells will stain very pink.
*The epithelium of the proximal tubule is a simple squamous epithelium.
*The proximal tubule demonstrates '''cells with brush border and basolateral membrane folding in order to increase its surface area'''.
**Note that during fixation, the brush border often sloughs off into the lumen.
*The proximal tubule is made up of the ''proximal convoluted tubule and then then proximal straight tubule''' which then proceeds into the descending loop of Henle.
**The proximal straight tubule '''continues through the outer stripe''' of the outer medulla.
**"Straight segments ... terminate at a remarkably uniform level ... that establishes the boundary between the inner and outer stripes of the outer ... medulla." per [http://en.wikipedia.org/wiki/Proximal_convoluted_tubule wikipedia]
**Note that this is true for both cortical- and juxtamedullar glomeruli-derived proximal straight tubules.

===Cell distinction along the PCT, LoH, and DCT===
*Recall that the cells of the PCT, LoH, and DCT are all epithelial cells specialized for reabsorption and / or secretion.
*There are four regions that can be distinguished by cell morphology and characteristic: PCT / thick descending limb, thin descending / thin ascending, thick ascending / DCT, and the collecting duct.
*Note that the thick descending tubule is the same as the proximal straight tubule; the same goes for the distal region: distal straight tubule = thick ascending tubule.

====Cells of the PCT and PST====
*Note that the '''PST = proximal straight tubule = thick descending / proximal loop'''.
*There are only epithelial cells in the PCT and thick descending loop.
*Epithelium of the PCT is a simple squamous epithelium.
*Recall that the PCT reabsorbs 70% of the filtrate; therefore it makes sense that '''the cells of the PCT and thick descending tubule are the only cells with a brush border'''.
*Cells of the PCT and thick descending tubule also have nuclei that are spaced far apart.
*PCT / thick descending tubule epithelial cells stain very pink.
*PCT / thick descending tubule cells are '''interdigitated'''.

====Cells of the thin descending and thin ascending tubules====
*There are only epithelial cells in the thin descending and ascending tubules.
*Recall that '''the descending loop is passively, highly permeable to water and solutes.'''
*Recall that '''the ascending loop is impermeable to water and actively secretes Na and Cl.'''
*The epithelial cells of the thin regions are thin cells that stain lightly.
*The nucleus of epithelial cells of the thin tubules is smaller than other nuclei of tubular epithelial cells.

====Cells of the DST and DCT tubules====
*Note that the DST = distal straight tubule = thick ascending / distal tubule.
*The epithelium of the DCT and thick ascending tubule is thicker than the PCT and thick descending tubule.
*There are three cell types in the thick ascending and DCT tubules: epithelial cells, macula densa cells, and principal cells.
*Recall that the thick ascending tubule and the DCT are the hormone-responsive regions with many ion transporters to reabsorb Na and Cl in exchange for K.
*The '''thick ascending tubule is called the "diluting segment" of the nephron''' because solutes are removed from the filtrate and the epithelium is not very permeable to water, thus making the filtrate more dilute as solutes are reabsorbed and water cannot follow.
**Water at the DST is pretty dilute: 60 mOsm relative to blood's 285 mOsm.
*The DCT is considered part of the LoH.
*Epithelial cells of the thick ascending tubule and DCT need lots of protein to facilitate ion transport and so it makes sense that '''thick ascending epithelium and DCT epithelium have lots of mitochondria'''.
*Epithelial cells of the thick ascending tubules and the DCT have '''apical nuclei that bulge outward''' (perhaps because of the mt that are pushing them apically).
*Recall that epithelial cells of the DCT will include macula densa cells.
**Macula densa cells appear at the last part of the thick ascending tubule.
**Macula densa cells stain darker than other epithelial cells and are more columnar.
**Macula densa cells are found at the '''vascular pole''' of the glomerulus, near the endothelial cells of the afferent arteriole.
**It makes sense that the urinepherous tubule's own DST is near its glomerulus because they started growing at the same time from the same location (recall the MET transition and uritogenic bud).
*The DCT is the first site of '''intercalated cells'''.

=====Differentiating PST and DST=====
*Thick descending and thick ascending can be differentiated by their stain and the intracellular location of their nuclei:
*Thick descending epithelium stain darker than thick ascending epithelium.
*Thick descending epithelium has more basally located nuclei while ascending epithelium have apically located nulcei.
*Thick descending has a thicker wall than the thick ascending.

=====PCT versus PST and DCT versus DST identification=====
*Note that PST and PCT can be differentiated because they are never found in the same location: PCT is in the convoluted area and PST is only in the medullary ray area.
*The DST and DCT cannot be differentiated because the DST spans the convoluted area and medullary ray area of the cortex and runs through the outer medulla. The DCT resides only in the cortex.
**Because the DCT and DST are both bound in the cortex, it is likely impossible to tell them apart (unless the structure in question runs right up next to a glomeruli and has macula densa at which point we know it is a DST).

http://www.ouhsc.edu/histology/Glass%20slides/35_10.jpg

http://www.medicalhistology.us/twiki/pub/Main/ChapterSeventeenSlides/b68_proximal_convoluted_tubule_kidney_40x_pas_labeled.jpg

=====Differentiationg PCT and DCT=====
*PCT and DCT can be distinguished by their stain and size:
*PCT epithelium has a brush border but DCT epithelium does not, though often the brush border is not preserved.
*PCT stains darker than DCT, though sometimes it can be the opposite, so good luck with that.
*PCT is made of larger cells than DCT (so with PCT you travel farther around the tubule before finding the next nucleus).

http://www.lab.anhb.uwa.edu.au/mb140/corepages/urinary/images/kidneydiagram.jpg

====Cells of the collecting duct====
*There are two types of epithelial cells in the collecting duct: principal cells and intercalated cells.
*Recall that the collecting duct's function is to reabsorb water--to concentrate the urine.
*Epithelial cells of the collecting duct are characterized by large, weakly staining (even clear) cells that bulge into the lumen.
*Epithelial cells of the collecting duct have clear distinctions between each cell and have nuclei that ''do not bulge'' (like PCT / thick ascending tubule epithelial cells).
*Nuclei are more basal and irregularly shaped.
*Principal cells are hormonally controlled for water reabsorption and are the '''major site of potassium regulation'''.
**Principal cells absorb Na and secrete K.
**Principal cells are generally impermeable to water but can become water absorptive when ADH is present (think AQ2).
*Intercalated cells '''stain darkly''', bulge a little into the lumen, have no brush border, have a more apical nucleus than principal cells, and are the site of pH regulation.

*There are '''three sections to the collecting duct''': the connecting tubule and cortical collecting tubule, the outer medullary collecting tubule, and the inner collecting tubule.
**The two proximal sections (connecting duct / cortical collecting duct and the outer medullary collecting duct) have principal '''and''' interstitial cells; the inner medullary collecting duct has '''only principal cells'''.
**The inner medullary collecting duct is also called the '''papillary collecting duct'''.
**The last section of the inner medullary collecting duct is called the '''duct of Bellini'''.

===Distinguishing regions of the kidney===
*Note that thin segments of the LoH and DCT / PCT never occur in the same area so they can be used to determine the origin of a section.
**'''Thin loops of Henle are only found in the medulla.'''
***Recall that the thick proximal tubule terminates at the outer-inner stripe border of the medulla.
**'''Convoluted tubules are only found in the medulla.'''
*Distinguishing the medulla:
**The inner medulla has only asc / desc thin tubules and the collecting duct.
**The inner stripe of the outer medulla has asc / desc thin tubules, proximal / distal thick tubules, and the collecting duct.
**The outer stripe of the outer medulla has only thick tubules and collecting duct.
*'''There are no glomeruli in the medulla!'''

*stopped here on 03/21/11.
*started here on 03/23/11.

==Urinary 2==

===Some details from Urinary 1===
*Recall that '''proximal tubule epithelial cells are eosinophilic and have central nuclei'''.
**Recall that the brush border is usually sloughed off.
*Recall that the proximal tubule has basolateral folds and a brush border to increase the surface area.
*Note the difference between the proximal convoluted tubule and the proximal straight tubule: the straight tubule descends through the outer medullary stripe while the proximal convoluted tubule is confined to the renal cortex.
*Technically the "glomerulus" is the group of capillaries in the capsule.

===Loop of Henle===
*Recall that the thin descending loop of Henle is permeable to water and solutes.
*Recall that the thin ascending loop of Henle is impermeable to water and active NaCl reabsorption occurs.
*Recall that the macula densa senses the amount of NaCl in the filtrate.
**When the NaCl level is high, we want slow the filtrate flow rate so we have time to reabsorb all that valuable NaCl; therefore, when the NaCl level in the filtrate is high macula densa cells release ATP to constrict the afferent arteriole and decrease GFR.
**Conversely, very little NaCl in the filtrate at the macula densa means that the filtrate has had lots of time to have its NaCl reabsorbed so we can speed up GFR. In this case, macula densa cells release prostaglandins that cause renin release (and subsequently vasodilation) at the afferent arteriole.

===More kidney superstructure===
*Filtrate is dumped into minor calyces which join to form major calicies, which form the renal pelvis, which join to form the pelvic hilum, which is continuous with the ureter.
http://www.comprehensive-kidney-facts.com/images/KidneyAnatomy.jpg
*Note that '''the ascending thick tubule is deeper than the descending thick tubule'''.
*'''Arcuate vessels''' follow the boundary of the cortex and medulla, giving off '''interlobular vessels''' that give off '''afferent arterioles''' and receive '''stellate vessels'''.
Do cortical nephrons really not have vasa recta?
True! Superficial (cortical) and mid-cortical glomeruli don't have vasa recta.
Furthermore, juxtamedullar glomeruli don't have peritubular capillaries.
See "Renal vasculature".
*Note that other than the blood vessels that go in and out of the glomerulus (afferent and efferent arterioles), the blood vessels are not specific to a certain nephron (urinepherous tubule); one vessel can service more than one tubule.
*The thick descending tubule = proximal straight tubule = pars recta.
*The human kidney is multilobar and '''each lobe has a single medulla called "pyramid"'''.
*The cortical tissue of adjacent pyramids (medulla) converge and also, together, run deep toward the renal hilum to form the '''columns of Bertin'''.
**Note that renal corpuscles can reside in these columns of Berin but their nephron segment will still reside in one of the neighboring medullary pyramids.
*Collecting ducts empty filtrate into the calyces at the '''papillary duct'''.
*Kidney stones (calcification or sedimentation of minerals) can form in the calyces of the kidney.
**We can remove kidney stones through a surgery that pierces the cortex, enters a calyx, and uses a probe to grab / destroy the stone. '''Percutaneous nephroscopy'''.
**Kidney stones are painful.
**Stones often form right on the tip of the papilla.

===Renal vasculature===
*The order of renal blood flow: renal artery -> inter''lobar'' artery -> arcuate artery -> cortical radial artery (imagine these radiating outward from the arc; used to be called interlo''bu''lar arteries) -> afferent arteriole -> glomerular capillaries -> efferent arteriole.
*The return route can start from two locations:
**Superficial and mid-cortical glomerulus: (from efferent arteriole) peritubular capillaries
***superficial peritubular capillaries return via stellate veins -> arcuate vein...
***deeper peritubular capillaries return via cortical radial vein -> arcuate vein...
**Juxtamedullary glomerulus: (from efferent arteriole) descending vasa recta -> ascending vasa recta -> arcuate vein...
*Then both follow the same path away from their respective nephron: arcuate vein -> inter''lobar'' vein -> renal vein.

http://biomed.brown.edu/Courses/BI108/BI108_2001_Groups/WAK/renalphys/images/image3.jpg

===Cortex organization===
*A '''renal lobule''' is a unit of renal tissue with medullary ray at the center with cortical radial vessels bounding it on the outsides.
*The cortex contains medullary rays, extensions of tubules from the medulla.
**"Under low power the cortex is divisible into alternating bands called the cortical labyrinth, which is recognized by the presence of numerous renal corpuscles and medullary rays, relatively straight collections of epithelial tubules oriented perpendicular to the capsule." per [http://ect.downstate.edu/courseware/histomanual/urinary.html SUNY Downstate Medical]
**So '''medullary rays are the ascending and descending tubules that will run perpendicular to the capsule of the kidney.'''
**So, '''a cortical labyrinth is a collection of renal corpuscles with their associated medullary rays'''.
**Note that in the cortex there is both DCT / PCT (which will run every which way) as well as proximal / distal straight tubules which will run down into the medulla. It is the straight tubules that form medullary rays within cortex cuts.

===Juxtuloglomerular apparatus and the renin-angiotensin pathway===
*Renin is released by granular cells (juxtaglomerrular cells).
**Renin cuts angiotensinogen into angiotensin 1 which is cut by angiotenins converting enzyme into angiotensin 2 (at the lungs).
**Angiotensin 2 causes systemic vasodilation.
**At the kidney, angiotensin2-caused vasodilation increases the GFR.
*Juxtaglomerular cells (granular cells) have granules full of renin; the granules can be seen in many slide preparations.
*The apparatus contains the afferent and efferent arterioles, the macula densa, and the extraglomerular cells (lacis cells).
**There are also juxtaglomerular cells which are '''smooth muscle / endocrine cells.'''
***Also called "granular cells".

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/notes/F16-5.jpg

http://allaboutim.webs.com/JGA%20-%203D.jpg

http://www.medicalhistology.us/twiki/pub/Main/ChapterSeventeenSlides/b67_macula_densa_renal_corpuscle_40x_he_labeled.jpg

===Post-kidney urinary ultrastructure===
*After the minor, then major calyces and the renal pelvis, filtrate (urine) enters the ureter, then the urinary bladder, then the urethra.
*The calyces, pelvis, ureters, bladder, and uretra all have the same histological structure.
**The only exception is that the walls of the ureters become thicker as they continue.
*The calyces through bladder are '''transitional epithelium''' with a '''lamina propria''' and '''smooth muscle'''.
**The urethra is sometimes transitional epithelium, too, depending on whether male or female.
**Transitional epithelium allows these structures to change volume easily, which is most obviously important in the bladder.
***Note that when no distended the cells look as if they are stacked on top of one another, then they are thin and spread out when distended.
***Transitional epithelium cells are characterized by a bulging apical surface ('''umbrella cells''') and may be bi- or poly- nucleate.
**The lamina propria holds the cells together with connective tissue when changing volume.
**The smooth muscle allows contraction for movement of urine along the tract.

===Transitional epithelium of the bladder===
*The transitional epithelium of the bladder has a special mechanism for expanding and contracting its surface area.
*Uroplakins can fold up like a pleat.
*A protein called '''uroplakin''' can be moved to the surface or removed from the surface via vesicular movement in order to increase or decrease surface area.
**Vesicles that contain uroplakin are called '''fusiform cytoplasmic vescicles'''.
*Uroplakin, as with all membrane proteins, is generated via the rER and golgi apparatus.
**We also know that there is some normal turnover of uroplakin; that is, there is an equilibrium of lysosomal-breakdown and rER-golgi-production.
What is "IC" and "UC" on slide 74.
*Where uroplakin is on the surface, the membrane is thicker; there are thinner areas of membrane that are distict in EM of bladder epithelium.

http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/bladder4.jpg

http://www.orienttumor.com/zh_asp_new/zt/ENGLISH/t&t/Bladder_Cancer/001_s.jpg

http://neuromedia.neurobio.ucla.edu/campbell/urinary/wp_images/49_transitional_epithelium.gif

===Smooth muscle of the bladder===
*Smooth muscle of the calyces, pelvis, and ureters are '''helical''' in pattern.
*Smooth muscle in the bladder is '''longitudinal''' and runs in all directions.

Be able to draw the whole urinipherous tubule and all the regions.

*stopped here on 03/23/11.

Practice exam for exam 2

149.166.25.152 — Wed, 02 Mar 2011 20:13:21 GMT

92.126.66.64: Qx3pvg Left on my site a link to this post. I think many people will be interested in it..!

*started here on 03/02/11 at 2PM.

*First half of alphabet in MS326 until 10:30,

Qx3pvg Left on my site a link to this post. I think many people will be interested in it..!

====Question 2====
*What is the shaded region?
**Portal space
*What is within?
**Portal triad: hepatic arteriole, portal venule, bile ductule '''and lymphatics'''

*Space of Diss has Ito cells which produce collagen.

====Question 3====
*Name these secretory structures.
**Ascini
*Name the organ (submandibular, sublingual, pancreas, parotid)
**Submandibular gland (b/c not many mucus cells--basally located nuclei and white mucus sacs)
**Could be parotid though, because most of parotid is serous; however, parotid will have some fat cells relative to mucus cells, too.
*What type of duct is this?
**Striated b/c specialized for ion transport so they have some striations b/c of lots of mt for protein pump production.
**Smallest is intercalated, then interlobular, and then striated.

*Myoepithelial cells are usually not visible without a special stain.

====Question 4====
*What region is this (in an epiphyseal plate--endochondrial ossification)?
**Region of ossification--can be differentiated from calcification region b/c of presence of lots of osteoblast cells
**Recall that proliferation region shows stacks b/c they have been mitotic.

====Question 5====
*Name the cell:
**Osteoclast (multiple nuclei, in a pit)
*Name the space in which it sits.
**Resorptive pit = Hawships lacunae
**There is a ruffled border where cathepsin K is and TRAP works.

*Clasts come from monocytes via RANKL signaling.

====Question 6====
*Identify this segment of the GI tract.
**Duodenum
*What is the gland?
**Brunner's glands
***Make mucus that is high in bicarb.
***In the submucosa

====Question 7====
*What explains the organization of cells and matrix in this region?
**Could be that the area hasn't been remodeled as osteons
**Osteoblasts on the insdie with osteoid below (not yet mineralized) which osteocytes and then osteons.
**Both bone lining and osteoblasts make up the endosteum lining.

====Question 8====
*Identify the stacked chondrocyte structures.
**Isogenous groups
*What type of cells are these.
**Chondrocytes
*What mechanism of growth has occurred.
**Interstitial growth
***Can occur b/c collagen is pliable (can't occur in mature bone)
*What type of collagen is found in the surrounding matrix.
**Type II collagen (found in all cartilage matrix)
**We know it is hyaline cartilage b/c we see no linear fibers.

====Question 9====
*What compartment or region is shown here?
**Primary ossification center (and also the marrow cavity within the diaphysis of the bone).
*What steps had to occur to get to this point of development?
**Cartilage model made
**Chondrocytes start to calcify their matrix, hypertrophy, apoptose, send out signals for vascularization.
**Bone collar forms (via apositional growth from osteoblasts)--really this is separate
**Vasculature invades and brings with it cells of osteogenic potential
**Osteoblasts convert cartilage to bone

====Question 10====
*Identify the organ.
**Pancreas (id'd by centroacinar cells)
*Name the structure
**Secretory ascini
*Name the cell type identified
**Centroacinar cells

====Question 11====
*What segment of the gi tract is this?
**SI
*What layers of the gut wall are contained within (the vili)?
**Mucosa, submucosa
*What are the folds of the wall called?
**Plicae circularis
*What plane of section is this?
**Longitudinal (b/c you see the circular layer of muscularis externa running in and out of the screen)

====Question 12====
*What segment of the GI trat is this?
**Stomach
*Which part of the stomach?
**Fundus (makes acids and digestive enzymes so it has very long glands)
***Neck and base of gland have parietal cells (fried eggs), chief cells.
**Has a muscularis mucosa

====Question 13====
*What is model of liver lobule is depicted?
**Portal lobule
*What does this portray?
**Bile flow

====Question 14====
*What segment of the GI tract is this?
**Colon
*What is this structure?
**Crypt of lieberkuhn = intestinal gland

====Question 15====
*Identify the structure at the arrow?
**Bile canaliculi
*What is the cell at the red and green arrows?
**Red = Kupffer cell
**Green = endothelial cells
*What separates the red and green cells?
**Perisinusoidal space (space of Disse).

====Question 16====
*what is the material at the arrow?
**Calcified cartilage matrix
***Recall that bone will be near the cells.

====Question 17====
*What segment of the GI tract is this?
**Tongue, within the oropharynx

====Question 18====
*What are the dark lines?
**Canaliculi, hold interstital fluid and filopodia of osteocytes.
*What do osteocytes do?
**Maintains osteon bone matrix

====Question 19====
*What explains the light dark pattern with polarization optics?
**Orientation of collagen fibers.

====Question 20====
*What gland is this?
**Under the circumvallae papillae
**A lingual serous gland
*Where do the excretory ducts of this gland open?
**Releases at the cleft.
*What is the nature of the secretory product and its function?
**Watery, proteiny product.
**Aids in taste by acting as a solvent.

====Question 21====
*What fiber type is contained in the matrix at the left that is not in the right?
**Elastic fibers
***Show up in orcein stain

*stopped here on 03/02/11 at 3:12PM.

Bone

149.166.25.248 — Mon, 21 Feb 2011 20:13:58 GMT

134.68.83.232: /* Intramembraneous bone formation */

*started here on 02/21/11 at 1PM.

==Bone and Cartilage==
*Starting a series of three lectures: today, Wednesday (development), and Monday (metabolic regulation).
*Chronic musculoskeletal issues are huge!

===Evaluating bone health in the clinical setting===
*Most important diagnostic is bone density imaging.
**DXA = dual energy xray a?
**We have a huge reference population on which to base our results.
**Disadvantages:
*High resolution CT scanners
**Pretty and pretty amazing
**Becoming more common

*Serum / urine biomarkers:
**These are markers that can help us know how much osteoblast and osteoclast activity and bone resorption activity.
**Go back to this list after the lecture.
**Don't need to know all of these

*Bone biopsy
**Take a coring tool, core out some from the iliac crest.
**Then take a histological slide.
**Not used very much.
**Used when biomarkers just don't tell you what you need to know.
**However, histology is very important for clinical trials

===Bone cells===

====Osteoclasts====
*Large
*Multiple nuclei
**More nuclei = more metabolically active
*Much larger than any surrounding cells
*Originate from hematopoietic lineage
**HSC sits in a macrophage CFU in the bone marrow
**Become monocites
**Stay in bone marrow
**Become osteoclast
**Rank ligand essential for diff into preosteoclast and full osteoclast.
*Rank ligand
**Made by osteoblasts
**Made by other cells of the bone marrow.
**Attaches to rank receptor on pre-osteocblasts
*Multiple osteoclasts fuse to form multinucleate
*OPG
**A decoy receptors for rank ligand
**Can keep osteoclasts from developing by sucking up all the rank ligand
*After maturation and getting to bone surface it starts to resorb bone
*Sealing zone is generated to attach firmly to the bone
**Allows the osteoclast to target where resorption will occur
**Compartmentalizes the enzymes
**Generates a "focal zone"
*Ruffled boarder is generated
**Increases the amount of surface area so enzymes can be pumped out of the cell onto the bone in high amounts.
*Enzymes for resorption:
**TRAP
***Tartrate-resistant alkaline phosphatase
***Can be assessed in blood to know how much activity of osteoclasts is occurring
**Cathepsin K
*Houshets lacuna
**Well in bone where resorption has occurred.

===Osteoblast===
*Located on bone surface
*Secrete osteoid
**Osteoid is unmineralized
*Osteoid ges minieralized eventually.
*Come from mesenchymal cells
**Need runks2 and ostrix
**Without you get no bone
*Runks2
*Ostrix
*Alkaline phosphatase is key protein involved in matrix production
*Osteoblasts become: osteocytes, bone lining cells, or it can undergo apoptosis.
*Osteoblasts secrete osteoid until their signal to secrete goes away then it beocmes one of thse three fates.
*Bone lining cells:
**Flattened
**Lay on bone surface
**Can still become activated
**In a nomral state, these cells line the entire bone.
**Signal can cause them to plump back up and resume bone formation.

===Osteocyte===
*Most abundant of cells of the bone
*Third cell within bone
*Impt for sensing signals within the bone
*These are terminally differentiated
*Surrounded by osteoid or mineralized matrix.
*MOst abundant of bone cells
*Connected to each other and to the bone surface by filopodial processes
**These live in channels called canaliculi
**Connected via gap junctions.
*There is one osteocyte per lacunae.
*Perform matrix maintenance and mechanics.
*This is an intricate network of osteocytes
**Trading nutrients
**Sending information

====Genetic profile differs from osteoblasts====
*Osteocyte cannot produce any more matrix
*Has different functions than the osteoblast
*Don't memorize the table
*Sclerostin is a gene unique to osteocytes and not osteoblasts.
**This shows up in late an osteocytes differentiation.
**It inhibits bone formation
**We are trying to develop drugs to inhibit sclerostin help grow bone.

===Bone matrix===
*Made of type 1 collagen.
**A fibrous collagen.
*Takes on a staggered arrangement.
**Mineral connects them end to end.
*The fibrils are highly crosslinked
**Promotes structural rigidity.
*Mineral interspersed also adds rigidity.
*Fragments of crosslinks can be used to measure bone turn over.
*C-propeptide in the blood means there is bone formation
When does collagen get cleaved?
From wikipedia:
1. Inside the cell
1. Two types of peptide chains are formed during translation on ribosomes along the rough endoplasmic reticulum (RER): alpha-1 and alpha-2 chains. These peptide chains (known as preprocollagen) have registration peptides on each end and a signal peptide.
2. Polypeptide chains are released into the lumen of the RER.
3. Signal peptides are cleaved inside the RER and the chains are now known as pro-alpha chains.
4. Hydroxylation of lysine and proline amino acids occurs inside the lumen. This process is dependent on ascorbic acid (Vitamin C) as a cofactor.
5. Glycosylation of specific hydroxylysine residues occurs.
6. Triple helical structure is formed inside the endoplasmic reticulum from each two alpha-1 chains and one alpha-2 chain.
7. Procollagen is shipped to the golgi apparatus, where it is packaged and secreted by exocytosis.
2. Outside the cell
1. Registration peptides are cleaved and tropocollagen is formed by procollagen peptidase.
2. Multiple tropocollagen molecules form collagen fibrils, via covalent cross-linking by lysyl oxidase which links hydroxylysine and lysine residues. Multiple collagen fibrils form into collagen fibers.
3. Collagen may be attached to cell membranes via several types of protein, including fibronectin and integrin.

*Collagen is formed in a twisted plywood formation.
**This gives strength to the bone.
**So its like people and they it is twisted in an orientation that will maximixe the structural integrity.

*Non-collagenous components:
**Know osteopontin, osteonectin, and ostecalcin
**Osteocalcin is a biomarker that can be measured in the blood to know how much osteoblast activity (bone formation) there is.

*Bone mineral
**Mineral goes between adjacent collagen fibers and in the space between.
**As it accumulates it first goes between length wise.

===Tyeps of bone tissue===

====Woven bone====
*AKA primary bone and Immature bone
*Not very common in the adult skeleton
*Found only when there is a bone injury or in some pathological state
*This is the type of bone that is formed when you need bone right now.
**Provides rapid stabiliation
*Not very organized
*Osteoid spit out in all directions
*Relatively low mechanical strength.

====Lamellar bone====
*AKA secondary bone, mature bone
*Most of the bone oin our bodies is this type
*Highly organized
**As mentioned above
*Formed slowly
*Higher mecanical strength than primary.
*Lamellae:
**Differing patterns of collagen organization
**Result in high birefringence
***The ability to refract light differently.
**This is a product of the alternating pattern of collagen fibers.

===Bone anatomy===
*Cortical or cancellous bone
**Cortical is called compact
***This is the outer part
***Main fxn is structural
***PRovide resistance to loading
**Cancellous bone = spongy bone = trabecular
***NOT squishy
***Small piece of cancellous and small piece of cortical would looke the same.
*Four different surfaces:
**Outer surface is called the periosteal surface
**Within are the cancellous surfaces
**Endocortical surface is the inside of the cortical surface.
**Within cortical bone are the haversion units.
**KNow the four surfaces

====Haversion systems====
*AKA osteons
*An osteon is a unit of bone that the osteoclasts have dug out and then replaced within the cortical unit of the bone.
*Within the haversion system is a space where the blood vessels and nerves flow.
*The center part of this '''haversiona canal''' is the ''central canal''.
**Run along the long axis of the bone
*Perferating canals = volkman (?) canals
**Go perpendicular to the long axis of the bone
**House vessels and nerves
*OUter edge of osteon is called the cement line.

====Periosteum====
*This layer is tightly adherent to the bone
*Both cellular and fibrous layers

====Endosteum====
*Endosteum is similar to periosteum but is on the inside of the bone
**Endostium '''has only cells'''.

===Structures===

====Lamellae====
*Concentric lamellae:
**These are concentric.
**Each ring from the outside of the bone in are called lamellae.
**Associated with a central canal.
*External circumferential lamellae
**Wrap all the way around the bone.
*Interstitail lamellae
**Within the bone tissue but not associated with central canals

==Cartilage==

*Cells are housed in lacunae which are surrounded by matrix.

===Hyline cartilage===
*Found in joints, respiratory passages, ends of ribs, within bones
*Made of type 2 collagen fibrils
*Has some non-collageneous proteins proteoglycan aggregates.
*Proteoglycan aggregates
**Have a central core
**Have some protein cores and then glycoaminoglycans hanging off.
*PG attract water and can therefore act as a shock absorber.

*Chondronectin
**Holds cells in place on the collagen and proteoglycans

*Condrocytes:
**Retain mitotic activity
***Unlike osteoclasts
**Can form 2, 4 or even more cells within its region.
**These units are called isogenous groups.

*Hyline matrix:
**It is not uniform.
**Terirtorial matrix = capsular
***Found just around a chondrocyte
***Capsule is found closer
**INterteritorial matrix
***Found farther out.
**The collagen fibrils are smaller in the territorial matrix
**The types of pg are different in the territorial than interterritorial.

*Perichondrium
**Fibrous tissue that lines the outside of hyline cartilage in most but not all locations of hyline cartilage
**Allows connection of muscle to cartilage
**Supplies the cells that can differentiate into chondroblasts (which diff into chondrocytes)

===Fibrocartilage===
*Found mostly in IV disks
*Has type 1 collagen in it.
**Forms fibers called rows or chords
*Between chords are the chondrocytes
*Has no perichondrium
*Can serve as a transition between tissues like tendon and bone.

===Elastic cartilage===
*Found in the ear, epiglottis, and the larynx
*Has type 2 collagen
**Fibrils
*Elastic fibers also present
*Has a pericondrium
*Looks much like hyline but you can see fibers in it.

*stopped here on 02/21/11 at 3PM.
*started here on 02/23/11 at 2PM.

==Concept review from Monday==
*Osteoblasts have three possible fates:
**Get encased in osteoid and become an osteocyte
**Apoptosis
**Cease activity and become an inactive osteoblast
***These are called bone lining cells; they are inactive osteoblasts.

*Osteocytes:
**These are osteoblasts that have become encased in the osteoid.
**Osteocytes are unique from osteoblasts in their genetic profile.
**Secretes slecerotsin (which osteoblasts no not) which inhibits osteoblasts.

*Cortical versus cancellous bone:
**If we take a small piece of bone out of the cancellous bone (like a single trabecula), it would have the same strength of a same size piece in the cortical bone.
**If you take a large piece of cancellous bone (like a whole chunk that looks like a sponge) it would be weaker than a similar chunk of crotical bone.

*Bone versus hyaline cartilage
**Cells: osteoblasts, osteoclasts, osteocytes / chondroblasts, chondrocytes
**Matrix: type 1 collagen, NCP, minerals / type 2 collagen, PG
**Matrix production: osteoblasts / chondroblasts or chondorcytes
**Cell-cell connections: osteoblasts, osteocytes / none
**Vasculature: central canals, perferoating canals, marrow, and periosteum / none
**Supporting tissue: periosteum / perichondrium

==Joints==

===Synarthroses===
*Very little movement
*Can be bone to bone or bone to hyline to bone or bone to fibrous to bone.

===Diarthrovidal (synovial) joints===
*Have a cavity with fluid
*Components: bone and cartilage of one long bone and a second long bone, and then the cavity space.

====Articular cartilage====
*This is hyline cartilage
*Articular cartilage has type 2 collagen with '''fibrils''' not ''fibers''.
*There are several zones:
**Superficial zone: in intimate contact with the cavity; has very few condrocytes; mostly type 2 collage fibrils; resists sheer forces
**Intermediate (transitional) zone: a transition from superficial to radial
**Radial (deep) zone: large number of chondrocytes; large number of collagen fibrils; compresses to absorb forces; lysogenous groups; interterritorial regions, etc.
**Calcified zone: interface between unminderalized cartilage of the radial and the subchondrial bone (first part of the zone); distinct from radial by way of tidemark
How do you tell the diff between calcified and non calcified cartilage?

====Joint capsule====
*Capsule is continuous with the periosteum
*Periostium has two layers: fibrous and cellular layer
*As it starts to cover the capsule, though, it loses it's cellular layer.
*Surface of the synovial membrane is not covered with epithelial cells
**A rare occurance in the body.
*Synovial membrane secretes fluid that makes the joint space.
**Gets nutrients to cells
**Acts as shock absorber

*Synoviocytes:
*Type A:
**Found on surface of the synovial membrane
**Look like epithelium but are not because they are not connected together.
**Act like macrophages to detect and phag foreign particles.
**Uusually 1 cell deep but can be 2 to 3 deep.
*Type B:
**Deeper within the matrix
**A fibroblast like cell
**Makes hyaluronic acid
**Look much like fibroblasts

*No perichondrium on ends of bones

====Osteoarthritis and Rheumatoid arthritis====
*AKA OA and RA
*OA:
**Mechanical
**Rubbing of bone without cartilage
*RA:
**INflammation occurs
**osteoclasts "wreak havoc" on the cavity

==Chondrogenesis==
*Chondrocytes produce matrix
*Then chondrocytes divide
*Interstitial growth verses appositional growth
**When matrix made "within" existing cartilage, the cells will separate from one another; this is how the bone is lengthened at the epiphyseal plates.
**When matrix is grown around a chondrocyte the cells do not move (adding new matrix onto a surface that already exists); used in lung tissue development.

==Intramembraneous bone formation==
*Much like cartilage development
*In craniofacial bones, mesenchymal cells get the signal to be osteoblasts, then aggregate to form a bone blastema.
*Then they secrete matrix to form the ''primary bone tissue'' with osteoblasts around the outside and some osteobalsts in the middle.
*Bone spicules are formed through intramembraneous ossification.
*How do you tell developing bone and cartilage apart?
**Lack of perichondrium (most cartilage has a perichondrium).
**Uneven activity indicates probalby not cartilage
**Matrix is less smooth in bone
*This is bone formation from scratch.

==Endochondrial bone formation==
*Here we start with a template on and in which we build bone.
**The template is hyline cartilage.
*The first step:
**Cells within the template, chondrocytes hypertrophy lending the adjacent matrix to calcification
**A bone collar forms by appositional growth (adding bone to a surface) on the surface of the hyline cartilage template
*Once the bone collar begins to form, the connective tissue above it becomes a periosteum.
**Regions without bone collar still have perichondrium
*Second, the bone collar is penetrated by an osteogenic (osteopenic) bud to start vascularizing the developing bone.
*Once penetrated and calcified cartilage in the middle is degraded, the area will be filled with bone.
**This is called the primary ossification center
**This region grows along the long axis of the bone.
**This is due in part to the activity at the epiphyseal plates.
*Third step occurs at the epiphyseal growth plates
**One at each en dof the developing bone
**Here is where bone lengthening happens
**There are 5 zones.
**Zone of rest: (shallowest from the articular surface to the middle of the bone): no activity by chondrocytes
**Zone of proliferation: chondrocytes become align and form rows and columns of chondrocytes (stacked coins) which contributes to bone growth as they push the entire bone unit to increase in length
***Can see rows of fairly flat chondrocytes.
**Zone of hypertrophy: all the chondrocytes hypertrophy; causes bone lengthening
***Has larger cells than proliferative, but still has a similar staining matrix (lightness versus darkness).
**Zone of calcified cartilage: chondrocytes start to die off as they can't get nutrients
***Distinct from the zone of hypertrophy because the matrix is much darker.
**Zone of ossification: bone formation on top of the calcified cartilage template; cartilage is resorbed by osteoclasts.
***Distinct from the zone of calcification because the matrix turns light again (but a little different coloring than the proliferative).

*Secondary ossification centers form
**This occurs when blood vessels benetrate distal to the epiphyseal plate
**So this are now has the same zones, though smaller.

*Growth plates fuse around puberty.

==Fracture healing==
*Two types: primary and secondary.

*Primary
**occurs when you have a very stable fracture; no movement (perhaps because of a plate and screws put in by orthopod).
**Then bone can form without fibrous tissue or cartilage formation.
**Can get osteons to remodel through the fractured zone.
**There is no additional tissue being formed (see secondary repair)
**osteoclasts dig out a region of bone...

*Secondary bone healing:
**Useful when fracture is unstalbe; whats happening when casted
**Bone '''and cartilage''' formation occur
**How exactly it works depends on how stable the fracture is:
***The more stable (the less strain) the less cartilage, the more bone.
***The more it moves, the more you need cartilage b/c cartilage can withstand stretching and movement.
**Just adjacent to the fracture the vasculature is disrupted.
**There is lots of cartilage formed here because it doesn't need vascular supply.
**Deepr in the boen you'll have bone formation
**Four stages:
**First: blood clot forms which facilitates the delivery of precursor cells that will help to heal the site (essential step).
**Second: formation of a soft callous and vascularization of the area.
***More strain means the callous will be more fibrous cartilage; low strain will have hyline cartilage; all are some combination of the two
**Third: form a hard callous via woven bone
***Woven bone occurs primarilly in injury because it is formed qucikly but is disorganized.
**Fourth: remodeling; removal of woven bone, replaced with lamellar bone.

*stopped here on 02/23/11 at 3PM.
*started here on 02/28/11 at 2PM.

==Bone remodeling==
*This is a balance of osteoblast and osteoclast activity.
*2/3 of bone gets resorbed each year.
*Just as we make new roads, the road starts to break down (cracks and such) until there are large potholes.
*YOu can fill it with asphalt but that don't last long.
*The better way is to remove a large chunk of the road and then resurface the entire area.

*Same thing happens with bone.
**Over a lifetime and with mechanical loading, we generate small cracks.
**These are called microcracks -- about 100 microns long.
**These are the result of daily loading on the bone.
*What does the skeleton do?
**It doesn't use glue or asphalt, it remodels the entire surrounding area.
**This is called '''bone remodeling'''.

===Remodeling steps===
*Think of the yellow box of a single trabeculae.
*It is covered with lining cells.
*Some signal causes activation of asite
**Brings osteoclasts to come to the site and start resorption.
*Once they have eaten a bunch, we reverse.
*Signals bring in osteoblasts to lay down new bone.
*Once filled back in (first with osteoid, then mineralized), you have a new-looking area and defects are gone.

===Cartoon===
*Note thtat this all occurs in a continuum.
*Death of osteocytes can signal for osteoclasts as can microcracks.
*The reversal zone is where the osteoclasts are not resorbing but the osteoblasts have yet to arrive.
*This process is not limited to trabechular bone but also in cortical bone.
*The osteoclasts can dig directly into a bone causing a central canal which will be filled in with osteoblast activity.

===Activation===
*This is the signaling for osteoclasts to come to the bone and start resorption.
*The two major signals are death of an osteocyte or a microcrack in the bone.
*The dark osteocytes are stained to pick up apoptosis markers, thus marking them as likely signals for osteoclast recruitment.
*Microdamage can signal, too:
**This is relatively normal for daily use.
**Provides protection against fracture by allowing small fractures and then repair; keeps large fractures from occuring.

===Resorption===
*Osteoclasts show up and seal (think sealing zone).
*What tells the osteoclasts to stop?
**We don't actually know.
**It may be the osteoclasts that are alive that say "hey, don't resorb me, I'm fine."

===Reversal===
*Osteoclasts leave or undergoe apoptosis.
*Osteoblasts arrive
*First the osteoblasts must clean up
**Clean up mess that the osteoclast leaves: collagen fragments flowing in the wind.
**They lay down a very thin matrix called the cement line.
**The cement line will be at the bottom of the well, then the osteoid is laid down on top of it.
*Then the osteoblasts lay down the normal lamellar bone
**Osteoid is laid down
**Mineralization occurs
*Once they reach near the normal bone surface, the last osteoblasts become lining cells.

*Entire process takes about 6 months.
**Typically; though can be modulated by some stuff.

*This process occurs at higher rates in the ribs and the jaw, probably because they are mechanically loaded more often.
*This process also explains how we get interstitial lamellae; they used to be a complete central canal with concentric lamellae until a portion of it got remodelled.

===Bone modeling===
*This is uncoupled: osteoblastas and clasts don't work in concert.
*So, osteoclasts may come in and remove bone and then thats it.
*IMportant in growth and development.
**Like elongating a bone: need to add at the far end and remove at the near end (if bone is growing away from you).
*Osteoclast deficiency demonstrates well:
**Get elongated, clubbed-shaped femur where osteoclasts haven't come in to do their part of shaping.
*Important for periostium, too.
**Periostium slowly gets larger over time.
**So this is a very slow modeling that adds material.

===Bone remodeling as a cause of bone mass loss===
*Cause of reduced bone mass is due to two factors of bone remodeling.
*First, osteoblasts get lazy over aging.
**So normally clast and blast activity is equal.
**But eventually the clasts dig out a little more than the blasts add back in.
**50-60 yo in women there is an increase in clast active sites (other than the normal clast > blast activity with aging).
***This causes increased loss because of increased number of sites, not because of a change in osteoblast to clast activity at a given site.
***Estrogen inhibits bone resorption so when estrogen goes away, bone resorption increases.
**Men
***Less osteoporsis b/c no loss of estrogen.
**This is true for both cortical and callous bone.

===Diagnostics===
*DXA
**Doesn't tell you anything about bone resoprtion and generation activity.
*Biomarkers
**Does provide clast and blast activity measurements.

===Pharma===
*We are concerned mostly with those people who show a low density.
*Anti-resorptives
**Here we are trying to stop clasta ctivity
**Disphophonates
**Estrogen and selective estrogen receptor modulators (SERMS)
***These adds back the osteoclast inhibiting effect of estrogen.
***SERMS are good becasue they focus on the osteoclasts and bone effects and not many of the other systemic effects that estrogen normally has.
**Cacitonin
***Not used often b/c the previous two are so successful.
**Denosumab
***A monoclonal antibody taht targets RANK-L.
***Recall that RANK-L is required for dev of osteoclasts
***Acts like OPG? (what was the endogenous decoy for RANK-L)?
**Think "rally with sally"
**These work by binding to the bone and inhibit osteoclast activity.
**These do not add bone per se because they don't activate osteoblasts
Do you get brittle ness from excessive caclification?
Do you those microcracks add up and make bone more likely to break?
**Reduce fractures 50-80%
*Anabolics
**Parathyroid hormone
***An anabolic agent
***When given pharmacologically, it builds bone.
***Even though endogenous PTH activates clasts.

==Ca, VitD, and Phosphate==

===Ca===
*Absorbed actively or passively in the small intestine.
*Active in jejunum
**Modulated by VitD
**Enterocytes increase CalvindinD in response to VitD; which allows the cytoplasm to hold more Ca and thus to absorb more.
*Without enough calcium you have rickets (in kids) and osteomalacia (in adults).
**Here the bone doesn't mineralize.
**DEformities occur
Does remodeling fix shape of bone over time if pt has rickets as a child?
**Rickets is reversible if you treat before closure of the growth plates.

====Regulation====
*PTH
**from parathyroid
**From chief cells = principle cells =
*Calcitonin
**from thyroid
What cell type?

*In response to low calcium,
**PTH increases
***STimulates osteoclast activity; increases Ca+
****Main effect
***Reduces Ca+ loss at urine
***INcreases CA+ absorption at the gut.
**Calcitonin decreases
***Allows more remodelling (less inhibitor activity).

====Remodelling====
*Some resorption is occurring without the specific location signaling of a microcrack.
**This type of resorption occurs wherever it can happen fastest b/c it is in response to low serum Ca levels.

====Hypercalcemia====
*This is a chronic increase in Ca++.
*Two etiologies: primary and secondary.
*Primary:
**Elevated PTH
**Perhaps because of a tumor or something
**Here we see that the duration of PTH exposure affects whether it stimulates clasts or blasts.
**When using PTH is used as pharam, it is pulsatile--fast rise, fast fall-- it stimulates osteoblasts.
**The mechanism for this is unknown.
**Excessive levels of Ca++ reabsorption at the kidney
**Increased VitD synthesis which feeds back to increase resorption
**Excessive resoprtion
**Call this '''pth mediated'''
**Treatment
***MOdulate the parathyroid gland

*SEcondary
**Three examples: toxic levels of VitD (absorb way too much ca at gut), immobilization (stimulates osteoclast activity; think space or bed-ridden), or malignancy.
**In immobilization, lots of clast activity which increases Ca levels.
**In malignancy, many cancer cells stimulate osteoclast activity which can result in hypercalcium.
**Tx:
***Use antiresorptive pharma.

====Hypocalcemia====
*Can come about from decreased PTH synthesis, secretion, or even PTH resistance.
*Can also come from low Ca diet.
*Some drugs can cause low Ca, too.
*TX:
**Increased Ca and VitD.

===VitD===
*Calbindin is required for good CA++ absorption at the gut and VitD is a txn factor modulating txn of Calbindin.
*Without enough sun light we may not get 7-choleterol... converted to inactive Vd3 (in circulation).
*Then we have to convert the vd3 to the 1 OH d2 at the liver and finally to the 1,25 OH d3 at the kidney.
*1 alpha hydroxylase at the kidney can be deficient to lead to VitD deficiency.
*Can also be sunlight and dietary deficient.
One last deficiency that I didn't catch.
*Ultimatley these cause osteomalacia and rickets.

===Phosphate===
*An impt mineral.
*REgulation is athe kidney
*ABsorbed in the duodenum
**Can be CA dependent or independ
**Also regulated by vitD.
*90% of PHosphate is filtered at the kidney and reabsorbed.
*Osteocytes secrete FGF23 and PTH from parathyroid act on kidney to reduce Na-Phosphate co-transporter
**Causes icnreased loss of phosphate.
*When phosphate is low:
**Vitd 1,25 goes up (increase resorption at the gut)
**PTH and FGF23 go down (decrease loss at the kidney)
*When phosphate high:
**vitd 1,25 is low (lower resportion at the gut)
**Increased PHT and fGF23 (increase loss at the kidney)

*stopped here on 02/28/11 at 3:05PM.

GI - Small intestine through anus

134.68.83.232 — Sat, 19 Feb 2011 17:04:04 GMT

149.166.24.19: /* Large intesstine */

*started here on 02/14/11 at 2PM.

==GI - Small intestine through anus==

===Esophagus review===
*All parts of the gut have four layers: mucosa (epithelia, lamina propria, and muscularis mucosi), submucosa, muscularis externa, serosa
*In the esophagus:
**epithelial is stratified squamous non keratinized
**No glands in the esophagus
**muscularis has longitudinal bundles that are discontinuous
**Sub mucosa has glands that secrete mucus
**Muscularis externa is composed of 1/3 skeletal, 1/3 mixed, 1/3 smooth muscle
***Each third has inner circular and out longitudinal
**Serosa: adventitia through thorax b/c not in pleural space, then once thorugh the diaphragm it gets a mesothelial covering

===Stomach===
*Has cardia region: a ring just around entry.
**We don't ahve to recognize this.
**Contains mucus glands.
*Fundus and body are next, and are similar.
**Have mucosal grlands: fundic glands = gastric glands = oxyntic glands (acid secreting)
**Cell types withing glands include stem cells, mucus neck cells, and parietal cells
*Stem cells:
**Reproduce all other types
**Live in the neck of the gland
*Mucus neck cells:
**Usuaqlly in neck
**Can't be distinguished versus stem cells
**Produce mucus
*Parietal cells = oxynctic cells
**In the neck
**Make acid and intrinsic factor
**Intrinsic factor binds b12 to protect fromn degradation so it can be absorbed later.
**Without factor I you have pernicious anemia (because it is hard to fix)

====Stomach images====
*Pits have the same surface mucuus cells.
*Glands have a different type of cell lining them.
*Neck region is the lighter staining area
**Neck cells include: parieta, mucosla, and stem cells.
*The neck region lives in the lamina propria.
*Need to identify the neck.
*Parietal cells:
**Tend to bulge out from the walls of the gland
**Look like fried eggs.
*Acid secretion:
**Occurs by fusion of tubulovesicles with a secretory canaliculus.
**Think of pushing your finger into the cyto; an invagination.
**When the tubulovesicles fuse they release lots of proton pumps that pump acid out into the ECF.
**Have lots of mt b/c make lots of proton pumps.
**Note that potassium is moved along with acid.
**Bicarb moves in the opposite direction of acid.

====Chief cells====
*Produce, store, and then secrete pepsinogen (a zymogen).
*Pepsinogen cleaves itself into pepsin.
*Breaks up proteins.
*Because of the zymogen granules they stain well with H.
*Granules are generally kept at the apical surface.

*Pairetal cells live in both the neck and the base of the gland.

=====Enteroendocrine cells=====
*ADUP-type (amine precursur uptake and decarobxylation): the name for production of hormone produced by these cells.
*Scattered through epithelium
*Produce ltos of endocrine secretion for local or global action.
*We cannot see these cells in our stains.
*There are several types:
**Defined as opened when apical surface reaches into the gland
**Open or closed
**Endocrine cells secrete toward the blood (their base) not toward the gland.

====Pylorus====
*Has deeper pits and shorter glands.
*Has lot sof mucus cell sint eh glands.
*In the pylorus, gastrin is secreted.

*Gland types:
**Cardiac, fundus, body: gastric glands
**Pylorus: deepr pits and mostly just mucus glands

===Small intestine===
*Has vili and crypts.
*The si is 12 to 24 feet as part of its specialization for absorption.
*There are folds to increase surface area (plicae circulares = valves of kerkring).
*There are vili (finger-like extensions of the epithlium) out into the lumen.
*There are absorptive cells with microvilli at their apical membrane.
*Absorptive cells are called enterocytes.
*Lots and lots of surface area!
*The muscularis mucosa and lamina propria are folded within the plicae circulares.
*The enterocytes are specialized for moving salt, water, amino acids, vitamins, sugar, etc.
*the caps within will carry the nutrients away.
*The cell interior of the enterocyte is usally negative (via Na/K atpase) so that the electro gradient can be used to run active transport of all the nutrients.
*Vilus is impt for nutrient absoprtion.
**Each has it's own arteries and veins.
**So within each is an isolated region.
**So as active enterocytes pump lots of nutrients in, the concentration of nutrients actually causes diffusion of nutrients from the vein to the arteries and vice versa for water.
**This causes a higher concentration of nutrient at the distal end.
*Enterocytes also absorb fat
**Absoprtion can only be performed as free fatty acids.
**Fat must be dispersed, not in the drops of fat as chyme has caused them to form into.
**So bile salts disrupt these droplets to form smaller pieces.
**Then smaller parts can be moved into apical membrane of the enterocyte, where they are put back into tAGs, put them into chylomicrons, and then secrete the chylomicrons through the basal membrane into the '''lymph system!'''
**Note that caps in the vili are pretty leaky (fenestrated) but not leaky enough for chylomicrons to get through, hence they gro throug the lymp.
**the central lacteal is where the chylomicrons of all the enterocytes of a singl3e lacteal are entering the lymph

====Goblet cells====
*Found on the surface of the vili
*Secret mucin

====M cells====
*Found at peyer's patches
*help transport antigens and abs for immune surveillance.
*Lymphocytes can migrate out between enterocytes, too.
*Lymphocytes can actually congregate somewhat inside the M cells, too.

====Enteroendocrine cell====
*Don't worry about table 15-1; don't memorize it!
*Don't worry about the table in the slides either.

====Glands of the si====
*These are simple tubular glands
*Called crypts of lieberkuhn.
*In both si and li but different.
*SI:
**crypts are the locaiton of stem cells
**Look for mitotic figures because this is where cells are dividing.
**At the very base are paneth cells
***Somewhat mysterious
***Have antibacterial agents, lysozymes, and defensins in eosinophilic granules.
***These are really eosinophilic.
***We think these chemicals released help control who gets to live in the gut.
***may be important for crohn's disease.
*Submucoals glands found only in the duodenum
**Called Brunner's glands
**Mostly mucus glands
**Mostly alkaline secretion (to counteract the acid secretion)
*Muscularis externa:
**Inner cicrular, outer longitudinal.
*Serosa of the SI:
**Retroperitoneal parts don't have mesophthelium but most does
*Nerve plexuses:
**Myenteric plexus = auerbach's: between the two layers 9of the musculara externa (inner cirular, outer longitudinal)
**Meissner's plexus = submucosa: runs within the submucosa
**Both are found in the large and small intestine.
**A plexus has little bundles that have nerve cells and then nerve material that connect them in a complicated way.
**Sometimes called the "little brain" of the gut because this is what controls the coordination of the muscle.
**Brain just says to speed up or slow down.

===Large intesstine===
*Cecum and colon are very similar.
*In the LI there are many long cryps of lieberkuhn and no submucosal glands
*Mucosa:
**There are simple columnar absorptive epithelial cells
**No paneth cells but instead there are undifferentiated cells
**There are lots of globlet cells which are easy to see.
**Colon has no vili that stick out but still has crypts.
**Colon serves to dry the feces and maintain salt balance.
**Also lubricates the feces with goblet cells.
*Muscularis externa:
**Has outer longitudinal muscle with special bands called tenia coli.
**Haustra are pouches that are formed.
**This is a thickening of outer longitudinal muscle bands.
**the poutches help hold the food material as it is turned into feces.

====Appendix====
*Looks much like colon.
*Exception: lots of lymphid molecules.

===Rectum===
*Lots of goblet cells.
*Moves from simple columnar to the stratified squamous of the skin.

===Cell turnover===
*3-6 days in SI
*4-8 days in LI
*Methotrexate experiment
**Causes cells to stop dividing:
**Dark cells are dividing
**Height of vili gets smaller when division is inhibited
***Vili slough off cells constantly so if they aren't replaced digestive problems occur.
***Both problems with uptake and with processing.
**After 4 days, division begins again; by 8 we are back nearly to normal structure.

*stopped here on 02/14/11 at 3PM.

==Lab==

GI - Glands

149.166.25.34 — Wed, 16 Feb 2011 20:01:46 GMT

149.166.25.34: Created page with '*started here on 02/16/11 at 2PM. *Be careful veryifying one's knowledge with online resources because they can be wrong. * ==Glands== *We'll do salivary, pancreas, and liver …'

*started here on 02/16/11 at 2PM.

*Be careful veryifying one's knowledge with online resources because they can be wrong.
*
==Glands==
*We'll do salivary, pancreas, and liver

===Salivary glands===
*Saw these with epithelium.
*Defined serous and mucus.
*Serous cells are only found in acinar, not in tubular.
*Mucus usually in tubular, sometimes in acinar strctures.
*Demilunes
**Here serous cells are found
*Two types of ducts:
**Intercalated
**Striated
*Also there are interlobular ducts in the connective tissue.
**Also called excretory

====Image(s)====
*Acinars are spherical so they will always be cut round.
*Tubules can get cut round or longitudinally (to be long).
*Recall that serous cells can have highly concentrated stuff in their granules so they stain dark but mucus canot be conncentrated in mucus cells.
*Tubules and acinar empty into intercalated tubes.

====Parotid glands====
*Have lots of serous acini
**Nuclei on the outside, granuels on the inside.
*Terculated ducts:
**Hard to find
**Tubular so they get longtudinally
**Smaller in diamter than acin
*Striated ducts
**Have lots of mt that sometimes give striations
***Not prominent
**Larger than terculated ducts

===Salivary===
*Three major are parotid (almost all serous cells), submandibular (mixed serous and mucous) and sublingual (more mucus than serous so will often look just mucus).

====Saliva====
*Low in Na because it helps the taste bud fxn.
*Alkaline, has bicarb to buffer acid
**Helps keep tooth decay reduction
*High in calcium and phosphate
**Helps re-mineralize the teeth.
**Mini-cavities form from bacteria but if you get it cleaned off, you can remineralize
*Protein components:
**alpha-amylase: starts breaking down carbs
**Proline rich protiens
***Abundant
***Antibacterial
***Help coat the tooth and keep bacteria off
**Lysozyme
***Lyses bacteria
**Mucus
***Lubrication
**Immunoglobulins
***Mostly IgA
***Secreted by epithelium into forming saliva
*Fear or nervousness can change the saliva
**Gets thicker

====Secretion====
*Serous produce fluid, protein, and zymogens
*Mucus produces mucins
*The products mix and then pass through intercalated ducts and then striated duct.
*Striated ducts are most important for removing most Na+.

====Summary====
*Most important is to know all glands have intercalated and striated and to know which type of secretion they generate.

===Pancreas===
*Two portions: endocrine and exocrine (acinar).

====Endocrine====
*Islets of langerhans (pancreatic islands) are groups of cells that produce insulin, glucagon, and somatostatin.
*Islets make up only 1-2% of pancreas the rest is exocrine.
*Beta = insulin
*Alpha = glucagon
*Alaph and beta make up most of the mass
*Delta = somatostatin
*alpha (20%), beta (70), d (5-10), F (1)
*F cells generate pancreatic polypeptide.

====Exocrine pancreas====
*Looks like the parotid in that it is made of acini.
**But has not fatty tissue
**Has no striated ducts
*Cholesystokinin = the hormone that moves the gallbladder
**Causes pancreas to secrete it's exocrine stuff.
**Makes sense because the two should operate at the same time.
*Proteases are the main product of serous cells in the pancreas:
**Trypsin
**Elastases
**Protease E
**Kallikrine
**alpha amylases
**Lipases
**nucleases
*Volume of fluid (water and salt) is secreted by ductal cells
*Secretin stimulates ductal cells to generate the volume (water and salt)
*Bicarb is scrected to keep the alkalinity hihg.
*Acute pancreatitis (inflammation or plugging of duct) is bad for the panreas
**When the cells break down the enzymes are let loose and they go nuts, destroying tissue.
*The ducts extend up itno the acinus
**Centroacinar cells = ductal cells that are up in the acinus
**Have a poorly staining cytoplasm and a light nucleus.
**Hard to find, honestly.
*Acinar cells:
**Well staining cyto and open nuc
**These cells have lots of rER and secretory granules.

===Liver===
*Largest gland in the body.
*Exocrine product is called bile.
*Bile is a nasty fluid:
**Amphopathic salts = bile acids, a form of detergent.
**Allow fat droplets to break up into small droplets
**Also contains waste products like pharma and bilirubin.
*Liver sees all the products from the GI tract before it gets to the blood.
**An importnat monitor and processor
*As blood passes through:
**Hepatocytes process: store, add, remove
**Microcirculation of the liver is special to facilitate secretion of albumins into blood. (Think sinusoidal caps).
*70-80% of the blood comes from the hapatic portal vein.
*The rest is oxygenated and comes from the hapatic artery.

====Hepatic blood flow====
*Blood flows between cords (a string of cells) or plates of hepatocytes.
*Blood spaces are sinusoids, a form of sinusoidal capillary
**Incompletely lined with endothelium; the endothelial cells don't bind to one another
**Makes them leaky
*Blood comes in in the hepatic vein or the hepatic artery, then flows together and mixes in the sinusoid.
*Then collected in central veins.
*Hepatocytes along the sinusoid is processing the lbood (taking things out and putting things in).
**They are also producing bile that goes the other direction as blood.
*The bile dumps into the bile duct system via the bile canaliculus.
*The bile in the canaliculus is simply flowing between cells, it is not within a structure.
*Portal triads are the hepatic veinule, the hapatic arteriole, and a branch of the bile duct.
**There may be more than one of each of these.
**Look for smooth muscle to identify the arteriole
**Look for simple cuboidal epithelium to ID the bile duct.
**The other things are the venules.
*When you see large spaces in the liver, consider it a blood sinusoid.
*Portal spaces also contain lymph vessels and nerves.
**CAn see vessels
***Usually look like empty space with practically no lining.
**Cannot see nerves

====Blood flow passed hepatocytes====
*Hepatocytes and blood are separated by the perisinusoidal space = space of Disse.
**Can get enlarged upon fixation.
*Fat storing cesll of Ito are in the perisinusoidal space.
*Kupffer cells are macrophages of the liver that reach into the sinusoidal spaces from the perisinusoidal space.
*Hepatocytes:
**Large nucleili
**Well staining cyto
*Kupfer cells are foundin the blood flowing sinusoid area

====Formation of bile====
*Bile flows within canaliculi which are formed by the hepatocytes themselves.
*At the edges of a lobule canaliculi merge into bile ductules.
**Ductules are lined with an epithelium.
**The small ones are called canals of Hering.
**These are the ducts that will add to the triad.
*The canaliculi show up as pin-holes between cells.
**They are NOT LINED with any cell except the neighboring hepatocytes.
**Tight junctions separate the membranes to form the canaliculus.
*In contrast, the ducts of hering and the larger ducts of the triad ACTUALLY HAVE an epithelial lining.
*Three ways to understand how hepatocytes filter blood and produce and bile:
**Liver can be lobulated:
***The classic lobule description
***The liver is divided into lobules that have protal veins, hepatic arteries and ducts at one side and
**Portal lobule
***Lobule is defined as all the hepatocytes that contribute bile to a given bile duct
**Hepatic acinus
***Lobule defined by hepatocytes' blood source
***Has zones: zone 1 is highly oxygenated and zone 3 is least oxygenated.
***After a meal, zone 1 will have the highest glucose level and zone 3 will have the lowest access to glucose.
***Also, metabolites generated by hepatocytes will be the opposite (highest in 1 and lowest in zone 3).

====The hapatocyte====
*Does lots of stuff.
*Produces bile salts:
**Detergents
**Made in sER
**Secreted across membrane of bile canaliculus
**Conjugated wtih glycine and taurine
**90% of the bile salt flowing out of a healthy liver is being recycled because they have been reabsorbed in the gut, then by the perisinusoidal membrane of the hepatocytes as blood from protal vein flows by.
*Many pharmaceuticals are secreted from the liver
**Often chemically transformed and then secreted into the bile
**Take some relative lipids soluble thing into your body, hepatocytes will get it from the blood, add a sugar onto it, then secret it into the bile.
**Includes bilirubin
*The processing often includes making the fat-soluble waste product water soluble so it can be carried to the kidney to be secreted via the urine.
**This is common and relevant to pharma.
*Hepatocytes also store glucose as glycogen
*Hepatocytes also produce most of the important serum proteins:
**Albumin:
***Can get secreted through sinusoidal cap wall
**lipoprotiens, glucose, urea.

===Gallbladder===
*The point is to store and concentrate the bile until fatty foods are present.
*Epithlium of gall bladder are simnple columnar epithelium
**Has brush border
**Absorb salt and water to concentrate the detergent bile
*Lamina propria is the CT below the epithelium
**Glands only found at the neck of the glall bladder.
*Muscularis:
**Sometimes a pouch of epithelium pokes thorugh and LOOKs like a gland but isn't.
*True serosis is present
*Bile gets sent to gall bladder because the commmon bile duct is usually constricted to cause back up into the bladder.

*stopped here on 02/16/11 at 2:03PM.

GI

149.166.178.254 — Wed, 09 Feb 2011 18:19:24 GMT

149.166.24.19: /* 1. Lip, slide 47 */

*started here on 02/09/2011 at 1PM.

==GI==
*The duodenum is where the pancreatic duct terminates as well as the bile duct.
**Bile salts are for emulsifying fats and foods.
*Jejunum and ilium are histo indistinguishable.
*Duodenum has some secretions that make it distinct
*LI:
**Cecum, colon, rectum
**Can't be visually discerned.

===Oral cavity===
*Lined with non-kera stratified epith.
**Still have nucleus and organelles.
*The oral cavity between the epithelium are the lamina propria and submucosa.
*There are small salivary glands.

====Lip====
*There is a skin surface.
**Red region is '''vermillion''' where the caps come to the surface.
**Mucus membrane on the tooth side.
*Notice that the skin is much thinner than the mucus.
**The epithelium against wet surfaces is usually thicker (mucus membrane).
*The vermillion is the hairless part of the epithelium.
*There are also glands.
*The transition from the keratinized part (outside skin) to non keratinized (musu membrane)
**Vermillion

====Hard palate====
*Parakeratinized = for dealing with rough surfaces
*Hard palate and tongue deal with lots of tough material.
*In the mucus mebrane, there are nuclei at the surface but stain a little differently.
**We call this parakeratinized.
**They stain differently because they are toughed to deal with rough food.

====Tongue====
*Bumps are called papillae.
*Filiform papillae provide roughness.
**Cats have very sharp, extended filiform papillae.
*Filiform are rod like and have a parakeratinized surface.
*Fungiform papillae have bulbous ends.
**These are the red bumps on our tongues.
**Fungiform DO NOT have parakeratinized.
*Circumvallate papillae
**In the back.
**Have a valley.
**Valleys are flushed by serous glands called glands of Von Ebner.
*Filiform and fungiform in the '''f'''ront.
*Circumvallae in the back.
*Foliate papillae
**Most humans have very few
**Leaf shaped.
**Not very useful.
*Geographic tongue
**2% of people have this
**Comes with eating certain foods.
**A kind of psoriasis of the tongue.
**In the red area, the filiform papillae have retracted.
**Edges of the ridges have enhanced thickness of the epithelium.

====Taste buds====
*Found especially around the circumvalae and in the middle of the fungiforms.
*5 kinds of tastes: staly, sweet, sour, bitter, umami (glutamate, freshness).
*Taste cells with receptors on the tip; communicate with afferents.
*Basal cells are the stem cell.
*There is a pore in the epithelial cells for each taste bud (only by EM).

====Gingiva====
*Gingiva = gums of the mouth.
**Very well connected to the tooth.
**The epithelial attachment of gottlieb is where the gum epithelial cells attach to the mineral surface of the tooth.
*Sulcus is the space measured to see if there is some pathology.
**Deeper = unhealthy (perhaps gingevitis).
*Enamel covers the crown.
**Mostly appetite
**96% calcium salts
**Has some proteins but '''no collagen'''.
**Proteins are secreted by ameloblasts during tooth development deep in the gums.
**And there's no replacing it!
**Laid down in rod shapes, packed very tightly; makes it very hard.
*Cementum covers the root.
**Cementocytes secrete this.
**Cementum is very much like bone.
*Tooth sits in the alveolus (a bony cavity).
**This bone goes through fast turn-over, making it a ''woven'' type of bone.
**Alveolus just means something that is shaped like a cucumber.
*Dentin
**Makes up the bulk of the tooth (into the root, up into the crown).
**Harder than bone.
**Matrix of Type I collagen
**Odontoblasts make dentin
**Odontoblasts reside in the pulp cavity and project through the dentinal tubules (dentinal processes).
***These tubules are problably how we detect hot and cold with our teeth.

=====Pulp cavity=====
*Extends to the apical foramen (hole at the bottom of the tooth root).
*The pulp cavity is inside the root and crown.

=====Periodontal ligament=====
*Run between cementum and the alveolar bone.
*A set of bundles of collagen bound at one end on the tooth cementum (root of the tooth) and to the alveolar bone (supporting bone).
*The ligament distributes the force of the tooth throughout the whole alveolus.
**Like a bicycle tire and spokes.
*This is a type I collagenous structure.
**When the structure is rope-like it is generally Type I.
*It turns over pretty quickly.
*Scurvvy: teeth fall out because ligament doesn't get regnerated becuase new collagen can't be generated.

===Gut tube===
*Mucosa is the inner-most layer of the tubular gut
*Then connective tissue: sub-mucosa
**Most nerves and blood vessels
*Muscularis externa
**Main muscle layer
**Thickest
*Serosa
**CT with or without mesothelium

====Mucosa====
*Three layers: epithelium, lamina propria (CT), muscularis mucosae
*Lamina propria = nearby layer.
*Muscularis mucosae = muslce of the mucosa

====Submucosa====
*CT
*Some glands
**Important for identifying some organs
*Arteries and nerves

====Muscularis====
*Missed this.

====Serosa====
*Technically means "CT with mesothelium".
*Without mesothelia, it is just an adventitia.

===Esophagus===
*Statified squamous non-ker epithelium (like oral cavity)
*Lamina propria:
**Has no glands (for the most part)
**Muscularis mucosae: has longitudinal muscle, not continuous
**Know these three properties!
*The submucosa '''does''' have glands
**Provide lubrication for the esophagus.
*Muscularis externus
**Have inner circular and outer longitudinal muscle layers
**In the upper 1/3 the muscle is skeletal
***Makes sense because the first part of swallowing is voluntary.
**in the middle third, mixed
**Lower third is smooth muscle
*Serosa
**Mostly just CT (adventitia)
**Where it penetrates the diagragm (last part), has a mesothelia covering (so a true serosa).

===Stomach===
*Txn from esoph to stomach: squamous non-kera epith to simple columnar epithelium.
*Also, we start to see tubular glands.
*There are four parts: cardia (ring where esoph and stomach meet), fundus, body (fundus and body look same histologically), and pylorus (looks different).
*Lned with surface mucus cells.
*Surface invaginates into pits where glands empty.
*Diff between pit and gland:
**Pit is an invagination, covered with surface mucous cells.
**Glands empty contents into pits; not made of surface mucus cells.
*Rugae are longitudinal folds in the stomach for expansion.
**A fold in the mucosa of the stomach.
**The whole mucosa folds up, not the muscularis externae.
**In the center is the submucosa.

*The cardia has pits with some mucusy glands.

*The fundus / body have glands with a neck and base (base stains more basophilically).
**At the base, staining dark are chief cells that make pepsinogen so they have lots of protein production and packaging stuff that makes them dark.
**Parietal cells of the fundus / body make acids.
***Sometimes have two nuclei.
**The neck region has parietal and undiffed cells.
**Base has parietal and chief cells.
***Recall that chief are much darker staining (basophilic).

*The pylorus has deep pits and shorter mucusy glands.

*Pylorus into the small intestine:
**Pits and glands convert into villi.

==Lab 15: Digestive Tract I==

===A. ORAL CAVITY.===

====1. Lip, slide 47====
*Note that the epidermis of skin on the outer surface is thinner than the epithelium on the mucosal surface.
*Contrast the appearance of the dermis and the connective tissue underlying the mucosa.
*Compare the epithelium and the accessory structures on each surface. The epithelium on the mucosal surface is non-keratinized.
*Glands beneath this epithelium are compound seromucous glands.
*The organization of the mucosa in the oral cavity is not as well defined (structurally) as the wall of the tubular gut. The oral mucosa has no muscularis mucosae, so that the lamina propria is continuous with the submucosa. This is difficult to see. We expect you to distinguish between lamina propria and submucosa in the tubular gut, but not in the oral cavity.
*The red margin of the lip may be difficult to detect. Dermal papillae are much taller here resulting in a thinner overlying epidermis. They also contain a prominent bed of capillaries.
**How does this affect the color of this region in life?

====2. Oral mucosa====
*Slide 43.
* uvula; and slide 46, soft palate. Both
*The oral surface is lined by non-keratinized stratified squamous epithelium
**(What type lines the respiratory surface?).
*The oral surface also displays large mucous glands deep to the lamina propria.
**What tissue type lies deep to the glands?
*Note that this portion of the tract lacks a muscularis mucosae and a muscularis extema.
*As with the lip, a submucosa will not be readily distinguishable from the lamina propria on these slides.
*What is the function of the mucosal glands of the labial, buccal and palatine surfaces?

====3. Tongue====
*Study slide 41 for general features of the lingual mucous membrane and musculature.
*Filiform papillae are abundant on the dorsal surface.
*The epithelium is described as parakeratinized-the top several layers are pale (similar to the stratum corneum of skin) but all cell layers have nuclei (no anucleate squames).
*Some slides will show one or more fungiform papillae.
**Do these have taste buds? Yes
**If so, where are they located?
*What type of muscle is found in the tongue?
*How does organization of these muscle fibers relate to the function of the tongue?
*Slide 42 contains a circwnvallate papilla.
*Where are the taste buds located?
*The serous glands of von Ebner are associated with this papilla.
*Find the secretory cells of these glands and the duct that carries their product to the surface of the tongue.

===B. ESOPHAGUS===
*The upper region of the esophagus is on slide 48 (adjacent to trachea); the lower region is
on slide 52.
*The esophagus is the first of the tubular organs of the G.I. tract.
*Identify the various layers in the wall according to the generalized scheme for tubular digestive organs (see Lecture Notes, text and atlas).
*What specific type is it?
*What kind of muscle is present in the muscularis mucosae?
**(This will be harder to see on slide 52.)
*Are there any mucosal glands?
*Are there any submucosal glands?
*Where do the ducts empty?
*Examine the muscularis extema.
**How many layers?
**What is the direction of the muscle fibers in each layer?
*Compare the muscle types in the upper and lower portions of this organ.
**What type of muscle is present in each portion? Is the adventitia covered by a mesothelium?

===C. STOMACH===

====1. Body and Fundus====
. Use slide 53 to initially study the various layers in the wall. What
are rugae? What layers ofthe wall are involved? Note that various planes of section through the
rugae can complicate the morphological appearance of the mucosa.
Histology of the mucosa: Compare the epithelial cells lining the luminal surface, the
gastric pits, and the gastric (fundic) glands. What are their respective secretions? Is a brush
border present on any of the cells? (no) Note that the glands discharge their secretion into the
base of the gastric pits, which carry it to the mucosal surface. Be able to distinguish between
chief and parietal cells at the histologic and ultrastructural levels ( ftnd examples of TEM' s in
your text and atlas- such as Basic Histology 15-22, 15-24). Know their typical location within
the gland, and their function. Also know that mucous neck cells and enteroendocrine cells occur
in the glands (identification not required). Gastric glands are found in the fundus and body of the
stomach.

====2. Pyloric Stomach====
. Slide 54 contains the distal portion ofthe body and the proximal
portion of the pyloric stomach. Compare the histology of the two regions. Pay particular
attention to the pyloric glands. What kind of cells make up this epithelium? Where is the
muscularis mucosae in relation to the pyloric glands? Enteroendocrine cells are present, but not
stained.
Slide 40 is a section through the pylorus showi.llg both pyloric stomach and duodenum.
(Note: The surface epithelium of the duodenum is missing in most of this specimen, but other
structures are well preserved.) What type of muscle forms the pyloric sphincter?
69

*stopped here on 02/09/2011 at 2PM.

20110131 10 respiratory notes

149.166.177.161 — Thu, 03 Feb 2011 21:31:42 GMT

76.28.242.138: oBG6ck I almost accidentally visited to this site, but stayed here for a long time. Stayed because everything was very interesting. Surely will share with all my friends!...

*started here on 01/31/11 at ?

LECTURE OBJECTIVES: RESPIRATORY SYSTEM
1.
Descnl>e the cells ofthe respiratory epithelium and know their function.

2.
Know the cells ofthe olfactory epithelium and understand how these cells function to sense smell.

3.
Traveling along the respiratory track from the nasal cavity to the alveoli, various segments have important histological characteristics. Be able to describe and distinguish the epithelium, unique cells, and the presence/absence ofcartilage, muscle, and glands for the various airway segments.

4.
Understand the structure and function oftype I and type ll cells ofthe alveolar system and how these cells contribute to the blood-air barrier.

5.
The respiratory vasculature functions to both re-oxygenate the blood and also to supply the respiratory tissue with oxygenated blood. Be able to describe the components ofthis network and their respective functions.

Page 2 of6
RESPIRATORY SYSTEM

Overall Structure and Function Air conduction, air filtration, gas exchange, smell, speech, endocrine, immune response
Two anatomical regions: Conducting-Nasal cavity to terminal bronchioles; function to condition inspired air Respiratory-Respiratory bronchioles to alveoli; function for respiratory gas exchange

Respiratory epithelium = majority of epithelium, ciliated pseudostrati:fied columnar
-Ciliated cells = most abundant cell; mucus transport
-Goblet cells = contribute to mucus production through their production ofmucin glycoproteins;
number increases during chronic irritation -Brush cells =microvilli; nerve endings -Basal cells= stem cells Metaplasia = transformation ofepithelium from one type to another; example is when respiratory
epithelium changes to stratified squamous due to chronic insult by turbulent flow (chronic cough
via bronchitis or smoking) Olfactory epithelium= located on the roofofthe nasal cavity (superior choncha); pseudostratified

-Olfactory cells =bipolar neurons,
ciliated (with odorant receptors)

-Supporting cells = microvilli, apical
nucleus

-Basal cells = single layer at
epithelium base, stem cell

-Bowman's gland= serous glands;
secretions contain odorant-binding
protein (OBP) which binds odorant
molecules, carries them to receptors
on specialized cilia

Conducting region
Nasal cavity= paired chambers separated by septum; comprised ofvestibule and nasal cavity
-Vestibule= contains vibrissae (nasal hairs); transition from keratinized stratified squamous epithelium from skin to respiratory epithelium ofthe remainder ofthe tract; sebaceous glands
-Nasal cavity (fossae)= three conchae (turbinates) the superior one contains olfactory epithelium; function to produce turbulent air flow; highly vascularized
Paranasal sinuses= cavities in facial bones; mucus travels to nasal cavity; prone to infection (sinusitis).
Phacynx = connects the nasal cavity to the larynx; segments are the nasophacynx and oropharynx
Larynx = connects pharynx to trachea; irregular shaped plates ofcartilage (hyaline & elastic)
Vestibular folds = (also called false vocal cords); two upper mucosal folds projecting into the lumen ofthe larynx
Vocal folds = (also called vocal cords); two lower mucosal folds projecting into lumen ofthe larynx; each fold contains a supporting ligament and skeletal muscle (vocalis muscle) which controls tension to produce sound; covered by stratified squamous epithelium (better at resisting abrasion from friction than respiratory epithelium)
Trachea= from base oflarynx. to start ofbronchial tree; hyaline cartilage rings in 'C' shaped pattern; perichondrium attached to trachealis muscle (smooth muscle) which serves to contract lumen Bronchial Tree = from bronchi to terminal bronchioles; progressive transition to smaller diameter
Primary bronchi {bronchus)= two; one enters each ofthe lungs at hilum
Bronchi= one for each lobe ofthe lung (two lobes in left lung, three in right); irregular cartilage plates
which decrease in size/number as tube gets smaller; contains circular layer ofsmooth muscle; abundant
mucous and serous glands
Bronchioles = no glands or cartilage but still has smooth muscle; some goblet cells; progressive transition from ciliated pseudostrati:fied columnar epithelium to ciliated simple columnar epithelium to cuboidal; final portion is called terminal bronchiole
Clara cells = secrete alveolar fluid which serves as the aqueous phase ofsurfactant
Asthma = airway hyperresonsiveness; bronchoconstriction ofsmooth muscle bundles

Respiratory region
Respiratory bronchioles =two or more arise from
each terminal bronchiole; similar to terminal bronchiole except wall is interrupted by alveoli; Clara cells can be present
Alveolar ducts = region oftube at which the respiratory bronchiole wall contains only alveoli; lined by squamous alveolar cells; contains smooth muscle and both elastic and reticular fibers
Alveolar sacs = collection ofalveoli at end of alveolar duct
Alveoli = saclike evaginations ofrespiratory structure; 02 and C02 exchange; lined by simple squamous epithelial cells (type I cells) and cuboidal cells (type II cells)
Interalveolar septum =wall separating two adjacent alveoli; display capillaries to create a minimal barrier to gas exchange; comprised of two layers ofsquamous epithelium between which are capillaries, connective tissue, leukocytes; alveolar pores connect adjacent alveoli;
Emphysema = permanent enlargement and wall destruction of air spaces distal to the terminal bronchioles. Breakdown is primarily due to loss ofelasticity (elastic fibers) via elastase (from neutrophils ). Various types classified by location ofeffect (either respiratory walls only or both respiratory walls and alveoli). Smoking is major cause
Pneumonia = bacterial infection in alveoli leading to inflammation and fluid accumulation

Respiratory lecture notes PageS of6

Cells ofthe alveolar system
-Type I {squamous alveolar cells)= flat cells that line majority ofalveolar surface; provide a minimum thickness barrier for gas exchange; contain both desmosomes and occluding junctions
-Type II (great alveolar or 'niche' cells) =cuboidal cells located in comers ofalveoli (groups of
2-3 cells); contain lamellar bodies which secrete pulmonary surfactant (acts to lower surface
tension such that less pressure is required to keep alveoli open); can differentiate to replace
injured type I cells

Neonatal respiratory distress syndrome (RDS) = surfactant deficiency in premature infants
(production begins at 35th week ofgestation); collapse of alveolar walls; treated with
corticosteroids which stimulates synthesis of surfactant or artificial surfactant.
-Alveolar macrophage (dust cell)= in alveolar septum and alveolar surfaces; remove degraded surfactant; either migrate up the bronchial tree or remain in the alveolar wall for life
-Endothelial cells= Thin, no fenestrations; express angiotensin-converting enzyme (important in control ofblood volume/pressure)
Alveolar
Nucleus of capillary connective endothelial cell tissue Nucleus of alveolar type I cell
Alveolus {Alveolar epithelium
Alveolar
type I cell

Fused basement membranes
Respiratory of the alveolar epithelium and
membrane the capillary endotheliur
Capillary endothelium

a b

Blood-air barrier
Separates air in alveoli from blood in capillaries (0.1 to 1.5 microns thick). Three components: 1) Surface lining and cytoplasm ofthe alveolar cells
2) Fused basement membrane ofthe alveolar and endothelial cells
3) Cytoplasm ofthe endothelial cell
Respiratory lecture notes
Page 6 of6

Pleura
Serous membrane covering the lung that serves to facilitate sliding during respiration
Two layers:
Parietal= lines inner surface ofthoracic cavity
Visceral = closely adherent to the lung.

Vasculature
Pulmonary arteries = contain deoxygenated blood; thin wall with low pressure; follows bronchial tree and branches to extensive capillary network in interalveolar septum; pulmonary veins (with oxygenated blood) are not closely associated with the bronchial tree and exit to the left atrium
Bronchial vessels = supply OA.)'genated blood to bronchial tree up to respiratory bronchioles where it merges with pulmonary arteries '
Lymphatic vessels =follow bronchi and pulmonary vessels, exit lung at the hilum

oBG6ck I almost accidentally visited to this site, but stayed here for a long time. Stayed because everything was very interesting. Surely will share with all my friends!...

20110126 07 lymphoid organs notes

24.15.60.132 — Mon, 31 Jan 2011 16:27:23 GMT

24.15.60.132:

*started here on 01/26/11 at 2PM.

==Lymphoid organs==
*Accent is from Argentina, not Arkansas
**Stop her with questions
*She was an immunologist, so she has a hard time '''not''' mentioning the immunology part of these tissues.
*Definition of lymphoid tissue: connective tissue enriched in lymphocytes.

===Lecture objectives===
*Enumerate the types of lymphoid organs
*Compare and contrast the histological characteristics of diffuse and nodular lymphoid tissues
*Describe the localization and the cell types that compose diffuse lymphoid tissue
*Describe the histological organization of the primary lymphoid organs
**Bone marrow (covered in the blood cells lecture)
**Thymus
*Describe the histological organization of secondary lymphoid organs
**MALT (mucosa associated lymphoid tissue):
***Peyer's patches
***tonsils
**encapsulated lymphoid organs:
***Lymph nodes
***Spleen

*We will not test over the immunology subject matter covered on pages 226-232 in your textbook (Basic Histology, 12th edition).

===Organs===
*Organs can be classified as primary or secondary
*Primary:
**Where lymphocytes mature
**Where they undergo antigen-indpendent maturation
**Bone marrow
***Where lymphocyte (NK, neuts, and T / B cell) precursors are generated
***More on Monday
**Thymus
***Where T cytes mature
*Secondary:
**Lymphocytes become activated
**Undergo antigen-dependent activation / maturation
**MALT
**Lymph nodes
**Spleen

*Organs can also be classified by their organization of the cells:
**If lymphycotes are not organized the tissue is called '''diffused'''
**Organized, round, masses called nodules or follicles characterize a tissue as being '''nodular'''.
***These nodules are mainly composed of B lymphocytes

===Connective tissue in lymphoid organs===
*Lymphoid tissue has particular cells and fibers to support lyphocytes
*Reticular fibers:
**See Bidwell's lecture.
**Type 3 collagen
**Dtermine mobility of cells int he tissue
**Cannot be seen in H&E; require silver staining
**Can be more or less packed; less or more mobility
**Can form trabiculae

===Cell type localization in lymphoid organs===
*No organization or localization in diffuse type tissue.
*Diffuse lymphoid tissue is generally associated with mucous membranes
*Nodular lymphoid tissue:
**Have nodules that form organization
**Some have centers that stain lighter; called germinal center
**Here the cells are activated and are actively dividing and thus have more cytoplasm and a lighter stain.
**Germinal centers are found in activated lymphoid nodules
**This is generation of plasma cells going on here.
**The nodules disappear after immune response is downgraded.

===Three cell types make up diffuse lymphoid tissues===
*Dendritic cells:
**Most potent APCs
**Engulf antigen, process in cyto, present on membrane
**Derived from bone marrow
**Stain red with blue nucleus
**They have dendrites (projections) to increase the SA that is exposed to the ECF so they can interact with lymphocytes
*Lymphocytes:
**B or T cells or NK
**Effectors of immune response
**We cannot tell the diff between B and T cells with LM or EM, must use specific antibodies agains surface prteoins.
***Can tell the difference once they are activated.
**B cells become plasma cells
***Have clock-face nucleus
***Have machinery to produce lots of protein
**T cells
*Plasma cells:
**Make IgA
***Can dimer
***Has a secretory piece so it can be secreted to gut and milk
**Activated B lymphocytes

===Describe the histological organization of the primary lymphoid organs===
*We will talk about bone marrow on monday.

====Thymus====
*Bilateral organ situated in the mediastinum.
*Location of T lymphocyte maturation.
*The thymus is active birth - puberty.
*After puberty, fat replaces the thymus.
*It has a particular structure with a cortex and medulla:
**It is surrounded by a connective tissue capsule.
**The capsule penetrates the parenchyma and divides it into incomplete lobules, each one with a cortex and a medulla.
**The capsule sends projections into the parachyma called trabeculae to form the lobules.
**The cells around the outside are the cortex and the cells in the middle are the medulla.
*The cortex contains immature T lymphocytes, macrophages, and stromal epithelial reticular cells.
**Here we can see that there's a fair bit of cytoplasm in the reticular cells.
**The reticular cells produce factors that help the lymphocytes mature and also provid physical support.
*The medulla contains differentiated (mature) T lymphocytes, epithelial reticular cells, and reticular fibrocytes.
**There are hallmark structures of the medulla formed by cellular debris and reticular cells called '''Hassall's corpuscles''' or ? corpuscles.
***These have no known function.
***Hassall's corpuscles consist of epithelial reticular cells in concentric circles with keratin filaments filling the cells.

=====Activity of the cortex and medulla=====
*The cells in the cortex, T cells undergo diff, maturation, and selection.
**Only the T cells that recognize the MHC survive.
*In the medulla there is negative selection
**T cells undergo apoptosis if they bind too strongly to the MHC.

*The cortex is isolated from circulation which is important so that T cells don't get away before they have been selected.
*There are three structures that generate this Thymocyte-Blood barrier:
**Continuous capillaries with tight junctions and a basal lamina; this keeps T cells from moving away aberantly.
**Reticularcytes (type I) that are bound to one another with desomsomes to help stop
**Perivascular connective tissue occupied by macrphages

*Mature T lymphocytes have moved through the cortex, into the medulla and can then escape into the blood via venules at the '''corticomedullary junction'''.
*There is no clear separation between the cortex and medulla; there is the cortico-medullar junction.
**This region has blood vessels (post-capillary venules), AKA high endothelial capillaries.
**These are lined by taller-than-usual endothelial cells and are the location where T cell exit the thymus.
*The boy in the bubble
**SCID pt, no B cell, T cell, or NK
**Mutation in the gamma chain of some receptor.
**Had a suit that he could use, too, to roam the world.
**He got a bone marrow transplant.
**Then got lymphoma becaue of CMV in the donor marrow.
***First connectinon between CMV and cancer.
**The thymus of patients with SCIDs is hypoblastic.
***Smaller than it should be.
***There is no epithelial cells in SCID thymus like there should be in the cortex.

===Describe the histological organization of secondary lymphoid organs===
*There are two types of secondary lymphoid organs: mucus-associated and encapsulated.

====MALT organziation====
*Stands for mucosa-associated lymphoid tissue
**These tissues are found in the GI tract, the respiratory tract, and the GU tract.
**These tissues have both '''diffuse''' lymphoid organization and a '''non-encapsulated'' or '''partially encapsulated''' aggregation.
*These are peyer's patches and tonsils and BALT
**Sometimes we call MALT tissue BALT or GALT because it is in the bronchial tissue or gastrointestinal tissue.

*Peyer's patches:
**Peyer's patches are non-encapsulated.
**They are large clusters of lymphoid follicles
**They are found in the ilium of the small intestine
**They are localized to the lamina propria and the submucosa
**They often produce a bulge into the gut.
**There are specialized M cells in the epithelium that covers the follicle.
**The M cells help transport antigens and microorganisms from the lumen to the APCs and lymphocytes of the peyer's patch.
***M cells present antigen to lymphocytes.
**M cells don't have brush borders.
**M cells have a little pocket below them, away from the lumen.

*Tonsils:
**Tonsils are considered partially encapsulated
***The capsule is only found on the side that faces the oral cavity.
***This is useful for keeping microorganisms out.
**This lymphoid tissue lies just below and in contact with the epithelium of the oral cavity
**There are three sets of tonsils:
***Palatine tonsils, pharyngeal tonsils, and lingual tonsils.
**Tonsils contain numerous lymphoid follicles with germinal centers.
***Recall: dividing cells, more cytoplasm, stain lighter
**Sometimes the lymphocyte proliferation is so large that we cannot see the epithelium.
**Look for '''crypts'''

====Encapsulated lymphoid organ organization====
*These are lymph nodes and the spleen
*The lymph nodes and spleen are encapsulated and organized.
*They contain immature and mature lymphocytes as well as accessory cells that surround.
*There is connective tissue forming a capsule around the organs.
*The arteries and veins of encapsulated organs pass through the hillum.

=====Lymph nodes=====
*The lymph nodes are bean shaped.
*They are found througout the body along the course of the lymphatic vessels.
*Lymph nodes contain lymphocytes, macrophages, and other APCs (like dendritic cells and B cells), as well as reticulocytes.
*The capsule is made of reticular fibers and sends of trabeculae that run into the bean shaped lymph node to form three distinct locations: cortex, medulla, paracortex.
*Cortex:
**Situated just under the capsule
**The cortex has reticular cells, macrophages, APCs, and lymphocytes
**The cortex also has lymphoid nodules with or without germinal centers.
**Germinal centers are found when antigen has been presented and B cell proliferation and activation are underway.
**There are '''subcapsular sinuses''' just below the capsule; these are formed by a reticular fiber mesh.
**The cortical sinuses run between the lymphoid nodules and communicate with the subcapsular sinuses.
*Medulla:
**There are two structures to the medulla of the lymph node: medullary cords and medullary sinuses
**The medullary cords contain mostly B cells, plasma cells, and macrophages.
**The sinuses contain lymph, lymphoctyes, and macrophages.
*Paracortex
**The paracortex does not have precise boundaries
**The paracortex will lack B cells yet accumulate T cells.
**There will be postcapillary venules ('''high endothelial cappillaries''') at the paracortical zone.
**These postcapillary venules will have exceptionally tall endothelial cells.

*Antigens and cells enter the lymph node through the afferent lymphatics and drain into the subcapsular sinuses and then into the cortical sinuses.
*The cells and antigens that have entered the cortical sinus can either leave the node completely via the efferent vessels or can enter the cortex proper to a B cell zone or T cell zone.
**At the B and T cell zones the cells can be activated.
*Efferent lymphatics contain:
**Activated B and T cells
**Abs
**Plasma cells

=====Spleen=====
*The spleen is the second type of encapsulated secondary lymphoid tissue.
**The first was the lymph node.
*The spleen is a non-essential organ so one can live without it.
*The spleen is the largest accumulation of lymphoid tissue.
*The spleen is involved in filtration of blood, destruction of old erythrocytes, and production of antibodies and activated lymphocytes.
*The spleen has a capsule that is formed by a dense connective tissue, just like the lymph node.
*Again, as with the lymph node, the capsule has trabeculae that come off the capsule to divide it into separate compartments.
**These trabeculae divide the parenchyma of the spleen (also called the splenic pulp).
*The splenic pulp has pretty much everything in it: B and T cells, APCs, macrophages, and reticular cells.
**It is considered a ''reticular tissue''.
*There are two components of pulp, named based on their color of fresh sections: white pulp and red pulp.
*White pulp:
**Looks bluish in staining
**Has nodules.
**Has periarteriolar lymphid sheaths (PALS)
***These are blood vessels covered with T cells
**Densely populated by T and B cells.
**There are marginal sinuses around the lymph nodules; this is where antigens arrive from circulation and APCs present to lymphocytes.
*Red pulp:
**Red pulp is composed almost exclusively of splenic cords (cords of Bilroth) and venous sinusoids.
**Sinusoids are spaces beween cords that contain blood cells.

======Blood flow in the spleen=====
*This is a special type of circulation.
*Blood enters the spleen through the splenic artery.
*The splenic artery branches to form '''trabecular arteries''' which give rise to '''central arteries''' which follow the trabeculae.
*The central arteries are surrounded by white pulp and the T cells within.
*After traveling past the white pulp, the arteries split again into penicular vessels.
**Now the blood is in the marginal sinuses of the white pulp.
*Penicular vessels are a specialized set of vessels that carry blood into the red pulp.
*Penicular vessels pass blood into '''sheathed capillaries'''.
**Sheathed capillaries are surrounded by macrophages, not by endothelial cells.
Does blood always go through sheathed caps or only in one of the two circulation options: open, closed?
*At the red pulp, blood splits it's flow: closed circulation or open circulation.
*Closed circulation:
**This type of circulation is called closed because the blood is continuously bound by endothelial cells of the vessel walls.
**In closed circulation, the penicullar arterioles and capillaries connect to the sinusoids.
**In closed circulation, macrophages reach between the endothelial cells to detect and destroy old erythrocytes.
*Open circulation:
**Open circulation allows blood to flow into the stroma of the splenic cords.
**The penicular arterioles are open-ended and thus let the blood flow directly into the splenic cords.
**In the stroma, macrophages destroy aged / abnormal erythrocytes or any erythrocyitic chunks floating about.
***Aged RBCs are targeted because their membrane is not flexible enough to let them get through the basement membrane of the sinusoids thorugh which they must pass if they want back into the circulation.
**Intact RBCs leave the stroma via trabecular veins and the splenic vein.
*In the white pulp, arterioles lead the blood to small sinuses that surround the PALS (periarterial lymphoid sheaths).
**In the PALS, blood and APCs intermingle and antigens are trapped and presented to lymphoid cells.

=====Splenomegaly=====
*Enlargement of the spleen.
*Must look within the spleen to understand what is going on.
*Can be diagnositic once you know what is accumulating within.

===Lab prep===
====Appendix====
*Non inflammed
**See the lamina propria
**Submucosa
*Enflammed
**Epithelium is eliminated
**Can see mitotically active lymphocytes
**Can see germinal center
**Can see how cells push epithelium into lumen
*CT will be found below epithelium.

====Tonsils====
*See the crypts

====Lymph node====
*Find hillus by way of vessels
*Find nodules
*Find cortex and medulla
*Find trabeculae
*Find pericoritical zone

====Spleen====
*Capsule, red and white pulp,
*Find sinuses, cords
*Lymphoid nodules

====Thymus====
*Nodules, cortex, medulla
*Cortex: Accumulation of lymphocyte precursors in cortex
*Medulla: lymphocytes, hassel corpuscles.
**Can see reticular cells, too

====Cervix====
*Has columnar epithelium, etc.

==Lab 8: Lymphoid tissue==
Laboratory 8: Lymphoid Organs
A. GUT ASSOCIATED LYMPHATIC TISSUE
Lymphoid tissue occurs along the gastrointestinal tract as a diffuse infiltrate of leukocytes
(primarily lymphocytes), as discrete foci or densly populated aggregates of cells (e.g. Peyer's
patches in the ileum), and as organs (e.g. tonsils).
Slide 59 appendix.
There are two sections on this slide, taken from different regions of the same appendix.
Start with the section that appears lighter in staining (contains fewer lymphocytes). Please take a
moment to look ahead in your atlas and text to the chapters that describe the intestines. Use a
diagram such as Fig. 15-2, 15-33, or 15-37 in Basic Histology to help defme layers of the gut
wall. Loose connective tissue subjacent to the gut epithelium occupies a layer called the lamina
propria, and is separated from a deeper region ofloose c.t. (i.e. the submucosa) by a narrow layer
of smooth muscle (i.e. muscularis mucosa). The lamina propria typically contains many
lymphocytes, and this is where you may fmd lymphoid nodules.
Look at the other, more lymphocyte-rich section. How have lymphocytes altered the
architecture of the organ? [For future reference, there are some excellent post-capillary venules
associated with the lymphoid nodules in this section.]
Peyer's Patch
Slide 60 ileum Peyer' s patch.
Peyer's patch is an extensive cluster of lymphoid nodules located in the wall of the ileum.
Lymphocytes can so heavily populate the lamina propria that the epithelium appears to rest atop
a dome. What is the position ofPeyer's patch relative to the mesentery (gross anatomical
structure)?
Tonsils
Slide 27 palatine tonsil.
Three sets of tonsils are located in the oral cavity and nasopharynx. We have a section of
the palatine tonsil. The lingual tonsil and pharyngeal tonsil (adenoids) have similar histology.
34
11127/10
This slide (slide 27) can be very difficult to navigate, as fixation is poor and it is lightly stained.
Make sure you look at an image of tonsil in your atlas (Basic Histology Fig. 14-15; Wheater
11.16). Use the scanning objective to locate the surface epithelium and intervening spaces called
tonsilar crypts (epithelium-lined). The epithelium that lines the crypts tends to be indistinct due
to heavy infiltration with lymphocytes. What is the orientation of lymphoid nodules and germinal
centers to the tonsilar crypts (here "crypt" means lumen of a fold in the mucosa)? What type of
lymphocyte occupies the nodule proper? What type of lymphocyte is found in intemodular
areas?
B. LYMPH NODE
Slide 24 lymph node human.
Slide 25 lymph node monkey.
Lymph nodes are encapsulated lymphoid organs. They have a dense collagenous
connective tissue capsule from which thin, collagenous trabeculae extend into the substance of
the node. The point where vessels and efferent lymphatics are located is called the hilus. Afferent
lymphatics can be seen in the capsule. The hilus is commonly indented (gives some nodes a
kidney bean shape). Note, in some of these slides (slide 24) there is a sectioning artifact. Do not
mistake this for the hilus.
Lymph nodes have a cortex, a paracortical zone and a medulla. There are no abrupt/rigid
boundaries between these regions. Instead, lymphoid nodules (some with germinal centers)
predominate in the cortex. The paracortical zone is the area immediately deep to the cortex, and
the medulla is innermost, a region made up primarily of lymphatic vascular channels and the
irregular cords (medullary cords) of tissue that surrounds them.
Look for mitotic lymphocytes in the germinal centers of the cortex. Which class of
lymphocyte predominates in the lymph node cortex?
Look deep to the nodules of the cortex to locate the paracortical zone. A definitive
marker of the lymph node paracortex is the postcapillary venule (also called "high endothelial
capillary"). These vessels are lined by extremely tall endothelial cells. Recall that PCV's can be
found in other lymphoid organs as well (e.g. intemodular areas of tonsil, appendix), but they are
fairly prominent here in the lymph node. What is the function of the postcapillary venule? What
class of lymphocyte surrounds them?
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Lymph nodes function as in-line ftlters for the lymphatic vasculature. Afferent
lymphatics join the node at its capsular surface, and efferent lymphatics leave the node at the
hilus. Because lymphatics are so delicate it is rare to find a patent afferent channel crossing the
capsule. Instead, you should see lymphatics running within the plane of the capsule. You can
distinguish lymphatics from blood vessels by their contents. If the lumen contains RBC's it is not
a lymphatic.
There are three lymph sinuses in the path that leads from the capsule to the hilus. Lymph
flows from afferent lymphatics in the capsule to the subcapsular (or cortical) sinus, to trabecular
sinuses that run along collagenous trabeculae, to medullary sinuses which lead to the efferent
lymphatics exiting at the hilus. Look for endothelial valves in the afferent and efferent
lymphatics. These valves help minimize backflow in this very low pressure system. Lymphatics
have little-to-no smooth muscle in their wall to regulate flow.
In slide 24, medullary sinuses have an eosinophilic background contributed by cytoplasm
of macrophages, fibroblasts and reticular fibrocytes. The medulla in this specimen is so heavily
populated by lymphocytes that it may be difficult to see the lumen of medullary sinuses. The
sinuses are flanked by densely-populated narrow cords of tissue (medullary cords). The cords are
also heavily populated by lymphocytes, such that it is very difficult to see the fibroblasts and
reticular fibrocytes that produce the fibrous framework of the node. Slide 22, which has far fewer
lymphocytes, is stained with Wilder's reticular stain, and the reticular fibers stain black.
Macrophages are an important cell type in lymph nodes. Slide 36 (leopard lymph node)
contains clusters of active macrophages marked by yellow-brown intracellular debris.
C. SPLEEN.
Turn to the diagrams and photomicrographs of the spleen in your text and atlas. Study
those references before you examine slide 26 and the demonstration slide of spleen. (Note: Don't
miss seeing this demonstration slide. It is far superior to slide 26.)
Slide 26 spleen.
The spleen is an encapsulated lymphoid organ that plays an important role in immune
response and the degradation of spent RBC's. Structure and function of the spleen is dominated
36
11127110
by the vasculature, and most of the structures we will emphasize are related to the pattern of
blood flow through the organ. The largest arteries and veins follow collagenous trabeculae that
extend inward from the capsule. These trabecular vessels (it is not necessary to distinguish
between arteries and veins) should be easy to fmd.
White Pulp: Arteries that branch from the trabeculae to enter the parenchyma of the spleen
are surrounded by lymphoid tissue. This lymphoid tissue-rich region is called white pulp. Look at
slide 26 with the inverted eyepiece. The white pulp appears blue (!), because it is heavily populated
by lymphocytes. At higher magnification look for germinal centers (areas ofB-cell amplification).
Textbooks describe narrow, thin-walled sinuses (i.e. marginal sinuses) at the periphery of germinal
centers in the spleen. These are not readily visible in slide 26 (identification not required). To the
side of (eccentric to) each germinal center locate a central arteriole (central artery of the white pulp).
Lymphocytes (mostly T-cells) that surround central arteries populate the periarteriolar lymphatic
sheath (PALS). Outside the PALS is the peripheral white pulp (PWP, mostly B-cells ). The boundary
between the PALS and PWP is indistinct.
Thus, white pulp structures include: central arterioles, periarteriolar lymphatic sheaths,
peripheral white pulp, germinal centers, marginal sinuses (identification not required for
marginal sinuses).
Red Pulp: Small arterioles leave the white pulp and lead to capillaries that perfuse the
surrounding, highly vascular red pulp. These arterioles and capillaries are not identifiable in this
slide. The red pulp consists of vascular spaces (splenic sinuses) surrounded by tissue (splenic
cords= cords ofBilroth). In slide 26 the spleen is engorged with RBC's, and against this
background it is very difficult (but not totally impossible) to distinguish between the splenic
sinuses and splenic cords.
Spleen demonstration slide: We have a slide (in short supply) that shows red pulp
structures much more clearly than slide 26. With this slide, identify the sinuses and cords. Look
for the elongated endothelial cells that line the sinuses. There are wide gaps between these cells,
and blood cells readily cross the wall to flow among the cells of the splenic cord. It is primarily
within the splenic cords that macrophages destroy aged RBC's.
Thus, red pulp structures include: arteries and capillaries of the red pulp (identification
not required), splenic sinusoids, splenic cords.
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D. THYMUS.
Slide 29 thymus human.
Slide 29 is thymus from a neonate. Observe the arrangement of each lobule into a cortex
and medulla. Are germinal centers present? Is a capsule present? The cells that form the stroma
of the thymus are called epithelial reticular cells. They are easiest to see in the medulla and
typically have large euchromatic nuclei surrounded by considerable cytoplasm.
Identify Hassall's corpuscles.
E. DIFFUSE, UNORGANIZED LYMPHOID TISSUE
Slide 81 cervix human.
You have already seen diffuse lymphoid tissue in the wall ofthe gut, where lymphocytes
have migrated to sites of antigenic challenge. When the lymphocytes are present in relatively
small numbers it is described as a diffuse infiltrate. When very large numbers of lymphocytes are
present, the cells can either be unorganized or they can form discrete nodules or follicles that
may contain germinal centers. Slide 81 of the cervix shows diffuse lymphoid tissue. Look for
lymphocytes (there are some good plasma cells here as well) in the connective tissue beneath the
epithelium, especially in the region where the vaginal epithelium (stratified squamous) joins the
epithelium of the cervical canal (simple columnar). You can see the cervical canal (unaided eye)
near the midline of the section.
38

*stopped here on 01/26/11 at 3PM.

20110124 06 connective cells notes

149.166.179.198 — Mon, 24 Jan 2011 19:53:56 GMT

192.162.19.21: fQfxNg Thanks for the blog post. Awesome.

*started here on 01/24/11 at 2PM.

fQfxNg Thanks for the blog post. Awesome.

==Laboratory 7: Blood==

===Prep===
*Look at the feathered edge.
*Scan at 10x.
*Find each type of blood cell in slide 18.
*In the colon (99), see lymphocytes and such in loose connective tissue.
*Look at bm (21) for lymphocytes.
**Hard to look at because hard to section.
**Look for large megakaryoctyes.
*Look for sinusoids in bm (21)
**Look for RBCs with macrophages surrounding them.
**Look for sinusoidal units.

===Peripheral blood===

====Slide 18 blood smear====
*Wright stain was used on this blood stain.
*RBC's ........................ pink.
**Nuclei. ........... absent.
*Neutrophils
**granules ................ small, pink to light purple.
**cytoplasm ............ .light pink.
**nucleus ................. lobulated, blue or purple.
*Eosinophils
**granules ................. large, red to orange.
**nucleus ................. .lobulated, blue or purple.
*Basophils
**granules ................. .large, dark blue to purple or black, often mask nucleus.
*Lymphocytes
**cytoplasm ............... light pink to deep blue, scant amount.
**nucleus .................... round, deep blue or purple
*Monocytes
**cytoplasm .............. gray to blue.
**nucleus ................. .less intense blue than lymphocyte, has open areas
*Platelets .......................... purple.
*A differential count is a count of 100 cells and then describing the percent of those 100 cells by their identities.
**Look in a field and identify the first 100 cells you see. Average the counts over four observations.
**See Basic Histology, table 12-2 for standard ranges.

====Slide 99 colon====
*locate regions of very loose connective tissue. Look, also, for cells within blood vessels.
*Neutrophils can be identified by their segmented nuclei.
*Eosinophils stand out because they contain bright red granules.
*Lymphocytes and plasma cells can be found in the loose connective tissue that lies beneath the colonic epithelium.

===BONE MARROW (MYELOID TISSUE)===

====Slide 21 bone marrow====
*also, Slide 8 bone marrow smear
*look for segments of thin-walled sinusoids.
**Look closely, as apparent channels running along trabecular bone surfaces may be separation artifact; the result of shrinkage and separation of soft tissue from the bone.
**The presence of RBC's can often help to identify sinusoids.
**The sinusoids show up as large blank circles with endothelial cells lining them.
**This makes sense because they are cross-sections.
*Identify megakaryocytes within medullary cords (tissue between sinusoids).
**These cells are large (~5X bigger than any surrounding cell).
*Look also within the cords for the intense red granulation that identifies cells of the eosinophil developmental series.

*Note: Slides 4 and 5 used in Lab 12 on bone formation contain sinusoids within fairly well-preserved regions of bone marrow.

====Slide 8 (marrow smear)====
*optional; however, this slide may be a good self-test of your understanding of blood cell development.
*identification of the various stages in erythrocyte and granulocyte development (considerable skill needed).
*We ask that you understand the structural features (and functional correlates) that distinguish the various stages of erythropoiesis and granulopoiesis.
*However, you are not required to identifY these cell stages in micrographs.

====Slide 18====
*Optional exercise: It is not uncommon to find late stages in erythrocyte or granulocyte development in a peripheral blood smear. lf you feel you have time, try going back to slide 18 (peripheral blood) to see if you can fmd immature cell stages.
*Polychromatophilic and orthochromatophilic erythroblasts
**Look for cells that are about the same size as an erythrocyte, but that still contain a nucleus.
*Neutrophilic band cells (stab cells) are relatively easy to find in slide 18.
**A key feature of the band cell is its "band" shaped nucleus (can be U, horseshoe shaped).
**Your text and the atlases each have good examples of these cell types.

*stopped here on 01/24/11 at 3PM.

20110119 05 connective tissue notes

149.166.178.9 — Wed, 19 Jan 2011 20:11:13 GMT

149.166.178.9:

*started here on 01/19/2011 at 2PM.

==Connective Tissue==
*Imagine the oldest person you know...naked. That's connective tissue deficiency.

===Medical case===
*Keith Richards
**Guitarist, rock musician.
*Sex and drugs and rock n' roll is embodied by Mr. Richards.

===Birth of rock n' roll===
*About 1940's.
*First rock stars were black.
*The girls loved these rock stars.
**And the boys tried to be like the rock stars.

===Age of the Bobby's or Elvis lite===
*Bobby Vee, Bobby Darin, Bobby Rudell, etc.

===Beatles===
*Beatles hit.
*Then things diversified a bit.
*We'll focus on British rock.

===The aging of Keith Richards===
*Three layers to the skin:
**epidermis (keratinized),
**dermis (collagen, elastic fibers, several cell types).
***Nourishes epidermis
***Forms barrier to the rest of the body.
***Involved in ion and water transport
**Subcutaneous fat
***Helps sculpt face.
***Stores TAGs
***An endocrine organ, too.
*All three give shape and structure to skin.

===Summer of love===
*Lots of drug use: lsd, cocaine, etc.

===Punk rock: the second British invasion===
*Sex pistols, elvis costello, etc.
*Less about music, more about chaos and noise.
**About lifestyle.
*Alcholol abuse
**Edema occurs because connective tissue cannot control water and ion passage

===Late 70s, early 80s===
*Richards: kept late hours, smoked, drank

===Twin study===
*Shows that twin that smokes have more wrinkles and lines in the face.
*This is called elastosis
**Collagena ndn elastic fibers are losing their strength.
*Shows that twin in southern climate has more sun damage
**Lines, wrinkles, folds.
**Due to damage of connective tissue proper layer.
*Shows that twin with excess weight can hide the lines and wrinkles and such.

===BritPop: The third british invasion===
*Punk rock is mainstreem.
**Radiohead
*Richard has deep lines, lossing elasticity in the neck.
**Looks like a turtle neck.
*Ground substance = glycoaminoglycans, among other fibers.
*Recent data says that wrinkles are caused by a change in cell population and composition of ground substance.

===Late 90s===
*Losing bone mineral density.
**Bone is a specialized connective tissue.
**Smoking and drinking will cause bone to be lost.
*Immune system is compromised.
*Swollen joints
**Cartilage and bone and synovial fluid all become inflamed.
**This is enhanced by drugs, sex, and rock and role.
*Excessive bruising is also a result of damaged connective tissue.

===Changes in connective tissue===
*Skin
**Wrinkling, less elastic.
*Fat gets redistributed
**This is important in storage of TAGs.
*Bone and cartilage:
**Decreased bone density
**Attenuated join mobility
*Blood
**Decreased immune system

===Section of skin===
*Pink ribbons are collage fibers.
**Note these are fib'''ers''' not fib'''rils''' which can only be seen in EM.
*Ground substance is a viscous fluid that helps hold everything together.
*Fibroblasts make fibers and ground substance.
*Macrophages are patrolling.
*Mast cells are around capillaries.

===Components of connective tissue===
*Study on your own.
*Separates proper connective tissue (today's topic) from the specialized types (bone, blood).

===Compnents of connective tissue===
*Visual organization of the types of connective tissue.

===Ground substance===
*Clear, viscous fluid, in between fibers.
*All components work together to act as an integrated hold.
*Made up of glycosaminoglycans and ...
*Glycosamino glycans:
**Put into aggregates via hylauronic acid.
*Glycosaminoglycans (GAGs)
**Long, linear polydisaccharides
**Consist of two different sugars
**Have lots of sulfur
***Except one:
**Know where these are found
**Typically linked to a core protein.
***There are multiple flavors.
***Syndecan (integral membrane protein)
***Versican (
***Aggrecan
**This aggregation makes them look like a bottle-brush.
**Typically about 800 units in length.
**Amino terminus:
***Has a hyluronic binding region; binds HA via linker protein.
**Over too units can bind to core protein.

**Proteoglycans "along with their GAGs" can be further associated with...
***This makes them huge.
***These are negative so they attrach positive ions and polar water like a sponge.
***this makes the aqueous fluid very viscous.
***This allows your joints to be cushioned.

====Another componetn of ground substance====
*Laminin (not lamin)
**3 peptides
**form a cross
**Binding sites for just about everything in the BM
***Type IV collagen
***Heparin sulfate
***Integrins
***Collagens, sulfates, lipids, etc.
**Molecular velcro
*Fibronectin
**Again, a velcro
**many binding sites

====Integrins====
*Dimeric proteins with alpha an dbeta subunit.
*Connect via talon on the inside of the membrane
*Signaling goes inward and outward.
*This is how the cell knows where it is and who its neighbors are and what it should be doing.

===Collagen===
*30% of our body by dry weight.
*21 genes
*Presence of collagens was critical to metazoans
**Ability to put body parts together.
*Gly-X-Y repeats are really impt.
**Forms a left handed helix.
**However, collagen is always found in triple helix turn that has a right handed turn.
*Type 1
**Two 11 chains and 1 12 ...?
*We need to know four of the 21 collagens: 1, 2, 3

====Fibrillar collagens====
*We need to knwo collagen 1, 2, and 3
*1, 2, and 3 for '''fibrils'''
**only visible in em
*1 and 3 also form collagen '''fibers'''
*Fibrils spontaneously line up in head to tail conformation
**Upon staining, fibrils will give distinct 67 nm periodicity.
**In an EM, this is a big hint that you're looking at some type of collagen.

====Type 4 collagen====
*Type 2 will be mentioned more in cartilage talks.
*Has gly-x-y repeats
*Has helical regions
**Interupted by non-helical regions
*Interuptions allow for flexible kinks.
*Head molecule allows for interaction with other collagen fibers.
**This allows for a network of type IV to be made.
**Thisis the foundation of the BM.
Get the name of the head.
*Perlecans help hold the mesh together.
*In mr. richard's wrinkeles, type 4 is dissappearing.

===Collagen synthesis===
*Just like any secretory protein.
**STarts on rER.
**Has signal peptide, called preprocollagen.
**Lysines are hydroxylated
***Requires vit c; survvy
**Glycosylation in ER
***Different types get different amounts of glyco...
**Signal peptide cliped
**Registration peptids allow proteins to line up to become triple helix
**Sent to golgi
**Sent to just inside the membrane

**Secreted
**Collagen lines up
Look at this in the book.

===Reticular fibers===
*thin, hard to see in H&E
*0.5 to 1 micron
*that's for type 3
*Type 1 reticular fiber is larger and easier.
*We stain with silver to turn sugars black.
*Found most readily in hematopoietic areas: spleen, lymph nodes, bm

===Elastic fibers===
*Collagen mediate tensile strength.
*Elastic fibers give stretch.
*Three stages in fiber synthesis

====State 1====
*Oxytalan fibers
*Made of ...
*Form scaffold for ?
*Resist stretch
*When oxytalon fibers are lost, skin just hangs.

====Stage 2====
*Elaunin
*At this stage, deposits of elastin are irregularlly place thorught he scaffold of oxytalan.
*Elastin is a globular protein with glycine and proline in it.
**Looks like natural rubber
*Elastin is secreted around these fibers.

====Stage 3====
*As secretion (by fb) continues, the elastin fibers crosslink (giving stretchability) and organizes in a regular way between fibrils.
*This gives skin the smooth and supple look.

===Sun exposure comparison===
*Black is ground substance.
*Changes at wrinkle
**Oxytalons are gone (usually rists stretching)
**Type 4 collagen atrophies
**Condroitin sulfate is starting to disappear (ground substance is disaapearting)
**Elastosis
***Collagen and elastin fibers are tangling and nonfunctional
***Elastins are thickening and not stretching
***Collagen is hardening and not bouncy.
*Fb differences:
**The superficial fbs are important in nourishing the tissue.
**In wrinkles, the superficial fbs are gone and replaced by deeper ones that aren't as good at providing for the tissue.

===Cells===
*We need to knwo the two stem cell pops from which connect tissue comes
**Fibroblasts: make ground and connective tissue
***Most important
**Adipocytes
**Osteoblasts

*HSCs
**Plasma cells and b lymphocytes and monocytes and macrophages and mast cells all come from this.

====Mesenchymal cells===
*Look for pale staining areas that don't look like anything.
**This is where you'll find non-committed mesenchymal stem cells.
*Pale nuc, clear.

====Fbs====
*Making ground subs, collagen, etc.
**So they are close to these things.
*Oblong nuc
*Euchromatic nuc when active

====Adipocytes====
*Look like chicken wire.
*Stians black with osmium.
*Look for some brown fat.
**It will have multiple lipid droplets.
*White fat is true storage of TAGs; brown fat is for heat generation.

====Macrophages====
Spaced out.
*These are different for each type of tissue.
**For now, know that they look for invaders in connective tissue.
*usually bigger than most cells around them.

====Would healing====
*three steps:
**inflammation
***Macrophages kill invaders, release cytokines, bring in wound-repair machinery
***FB important for cell proliferaiton

*step 2?
**Main player?
**Remodeling
***FB are the main soldiers in remodeling.

====Mast cells====
*In connective tissue
*In dermis and capillaries
*In breast sections
*Often have metachromatic (blue toluene makes them reddish-purplish) color
*Seretory granules have mediators to hypersensitivity:
**histamines, condroitin sulfate (parasites), etc.
*Immediate hypersensitivity: read the small sectionin the book.
*OfGten scattered around the cell.
*Granules seen by focusing upand down.

====Plasma cells====
*Lymphocytes that make Ab
*Found near glandular tissue
*Eccetnrically located nuc (like mast cells)
**Clockface (what?), looks like polka-dots to me.
*Pale staining golgi
*Lymphocytes are almost all nuc and very heterochromatic

===Loose connective tissue versus dense===
*Loose connetive:
**Fibers in all directions
**Quite cellular: mcf, fb
**Lots of ground substance (or where it was)
**Near epithelial layers
**Orcein stain will show elastin fibers
***Elastin can be made in sheets in that form the lamina in smooth muscle of arteries.
*Dense irregular
**Not as many cells
**Less ground substance (or white space)
**No specific orientation
**Lower part of dermis
*Dense regular tissue
**Tendons and ligaments
**All fibers in one direction
**Very little ground substance
**All nuclei lined up in the same direction.
***They are very elongated.

==Lab 5: Connective Tissue==

===Objectives:===
#Compare the characteristics, and relative abundance of fibers, cells, and ground substance in each of the connective tissues.
#Be able to identify the various connective tissue types.

===CONNECTIVE TISSUE FIBERS===

====Collagen fibers====
*Collagen stains pink upon H&E staining.

=====Loose connective tissue=====
*Examples of loose connective tissue include jejunum, just deep to the mucosal tissue and in the trachea, just deep to the epithelial layers.
*Slide 48 trachea
**H&E
**Connective tissue is subjacent to the epithelium.
**Pink ribbons are aparent.
**Nuclei identify the fibroblasts within the ribbons.
*Slide 95 jejunum
**H&E
**Connective tissue of the submucosa
*Slide 97 jejunum
**Masson's trichrome stain
**Collagen stains blue

=====Dense irregular C.T.=====
*Slide 31 palmar skin
**Note the reticular dermis (see Basic Histology 18-1, Wheater 9.12) which shows the nice wavy ribbons of collagen as opposed to swirls and irregularity.
**The papillary layer was thinner than I expected.
**The difference between papillary and reticular layers was much less than I expected.
**One difference was that reticular seemed to have thicker fibers, even if they weren't that much less squiggly.

=====Dense regular C. T.=====
*Slide 1 tendon
*Note that the tissue is very homogenous because all the fibers lie in paralle.

====Elastic fibers====
*Elastic fibers are difficult to find because they are found in such small quantities and do not stain well.
**Look for them in large arteries or prominent elastic lamina where they are most concentrated.
**Use orcein to stain elastic fibers brown or black.
*Slide 10: Mesentery
**Here elastic fibers can be seen as black on the double stained orcein and H&E.
**The elastic fibers are present in both the vessel wall and in the loose connective tissue.
***Elastic fibers in the walls of the arteries form thick layers called "lamanae".
**Note that the elastic fibers are much thinner and more defined that the wide, wispy collagen fibers.

*Slides 48 (Trachea) and 31 (skin) have elastic fibers but without orcein, they are difficult to see.

====Reticular fibers====
*These fibers stain black by silver impregnation techniques (i.e. are argyrophilic).

=====Reticular connective tissue=====
*Slide 22: lymph node
**Uses a Wilder's reticular stain
**Reticular fibers are small enough that they are best seen on the highest power.
***Reticular fibers are black
***Collagen fibers are brown
*Most reticular connective tissue is made up of reticular fibers.
*Reticular connective tissue is found both in and around the node.

=====Embryonic connective tissue (Mesenchyme)=====
*Mesenchyme is located between developing skin, muscle, and bone.
*The major component is reticular fibers which are difficult to see in many sections.
**Look for areas where the cells can be seen as distinct, individual cells.
**Turn the light down, too.
*Mesenchyme will look like mostly empty space with widely distributed cells sending off thing tendrils.

*Slide 4: Fetal limb:

*Slide 39: Fetal jaw:

===THE CELLS OF CONNECTIVE TISSUE===

====Fibroblasts====
*Slide 31: skin
**Look for the dense connective tissue below the stratifed squamous keratinized epithelium.
**Fibroblasts can be seen as elongated, deep-purple stained cells.
*Note that nuclei with less staining have more euchromatin and therefore are more active than those with darker staining.
*Furthermore, active cells will be larger.

====Plasma cells====
*Plasma cell characteristics:
**eccentric nucleus,
**clock-face nucleus (chromatin clumped toward the periphery, like numbers on a clock),
**pale staining golgi region, (next to the nucleus)
**'''basophilic cytoplasm''' that stains smooth and not grainy
*Other cells that are found in the connective tissue include:
**Macrophages (won't have clock-face nuc, will have extensions of cytoplasm)
**Mast cells (will have granules)
**Basophils (will have ganules)
*Other clumped nuclei-containing cells are lymphocytes but B and T cells cannot be differentiated in H&E, usually.

*Slide 43: uvula

====Lymphocytes====
*Lymphocytes are found in loose connective tissue of the gut and respiratory tract and in lymphoid organs like the spleen, gut, and lymph nodes.
*Most lymphocytes are dominated by the nucleus, and may have just a thin rim of cytoplasm.

*Slide 24 lymph node
**The densely packed areas of cells are called '''lymphoid nodules'''

*Slide 43: Uvula
**A good place to find fibroblasts and lymphocytes.

====Macrophages====
*This stain is achieved by letting the macrophages injest carbon particles, making the macrophages black.

*Slide 36 leopard lymph node

====Adipose Cells====
*Adipose cells can occur singly or in clusters.
*Fat cells are seen as vacancy with a thin rim of cytoplasm when sections are prepared via formalin fixation (with dehydration with alcohol and xylene).

*Slide 78 mammary gland:
**Note that the ducts are lined with simple, two-layer cuboidal epithelium.
**This mammary tissue contains loose irregular and dense irregular connective tissue as well as adipose tissue.

*Slides 30, 31 skin:

*Slide 9 sciatic nerve (osmium fixed):
**Fixed with osmium tetroxide to preserve the lipid as black.

====Mast Cells====
*Mast cells have cytoplasmic granules.
**These usually do not show up in H&E sections.
**Often the cells appear to be broken, to have spilled their granules.
*See Wheater 4.18; Gartner plates 3-3, 3-5, 3-6; Basic Histology 5-5.

*Slide 78:
**look for cells with a
***round nucleus,
***cytoplasm that is filled with small reddish granules.

*stopped here on 01/19/2011 at 3PM.

20110112 04 notes.txt

24.15.60.132 — Mon, 17 Jan 2011 21:32:58 GMT

76.180.225.61: xXVlVc Good post! Found a lot of new and interesting! Will share the link with others:D

*started here on 01/12/11

==Circulatory==
*First time we'll see tissues put together into tissues and organs.

===Objectives===
*At the conclusion ofthe unit on the circulatory system, each student should be able to:
**Sketch from memory the histologic structure of all ofthe vessels. Label the tunicae.
**Distinguish the relative functions of the parts ofthe vascular system, and correlate these with their structures.
**Describe the physical relationship ofpericytes to endothelial cells.
**List the four types of capillary and describe their similarities and differences. How do these differences relate to function?
**Describe the function of precapillary sphincters and arteriovenous anastomoses.
**List the metabolic functions ofendothelial cells, as described in the text.
**List the layers ofthe heart and distinguish between atrium and ventricle in the structures ofthese layers.
**Describe the specialized cells ofthe heart.
**Compare and contrast lymphatic vessels with blood vessels with regard to structure and function.

===Components===
*Heart
**Pumps to two systmes at once
**Has variable output and speed
***Yes, output, asin the volume
*Artieries
**Low capacity: hold little of the total blood
**Carry at high hydrostatic pressure
*Capillaries
**Low hydrostatic pressure
**High cross-sectional area
**Low flow velocity
**Good chance for diffusion with fluid around caps
*Veins
**Very Low hydrostatic pressure
**High and variable capacity
***Can hold 75% or can contract to hold less volume (if dehydrated) or expand (if well hydrated).

===Functions===
*Draw a heart, divide with two lines to make four sections.
**Atria and ventricles
*Blood goes out left ventrical to systemic capillaries (everything but the lungs)
*Blood comes back into venules and veins and right atrium.
*Then to right ventricle and to the pulomonary system (the lungs)
**We won't talk about pulmonary vessels this lecture.
**Theya re different because their pressure is different.
*Back into left atria and ventricle

===Histology of vessels===
*The vessels have layers, called tunics.
**Tunics were garmets, tight-fitting shirts.
*Layer closest to the blood is ''tunica intima''.
*Outside most layer is called ''tunica adventitia'' or ''tunica externa''.
**The layer that '''comes to''' the outside of the vessel.
*In between is the ''tuica intermedia''
**Contains muscle
*Vessels can have vessels in them: ''vasa vesorum'' (vessels of the vessels)
**This is to supply the outer cells of the bigger vessels.
*When we see smooth muscle in the vessels, there is probably innervation
**We usually won't see the nerves, though, because they are so small.

===Capillaries===
*Capillaries are about 10 microns, so blood cells just barely fit thorugh.
**In smaller capillaries, RBCs even have to change their shape and squeeze through.
*Not all capillaries are the same
**Different degree of permeability depending on where they are in the body.
**Thinner, more holes = more permeability
*Recall that a cell membrane is about 10 nm with proteins in it.
*Recall that we can see about 1 micron things as points via LM.
*Capilarries are usually 7-10 microns in diameter.
*They only have the tunica intima.
*Sometimes have pericytes with them
**Can replace other cells
**Can form new blood vessels
**Can undergo division
*Caps are simple squamous epithelium
*Continuous capilarries:
**Have a relatively thick (though very thin) extension of cytoplasm
**Found in muscle, nerve, connective tissue, and exocrine glands
***Like salivary glands seen on monday.
*Fenestrated capilarries
**Have windows = fenetre in french
**Found in kidney, GI, and endocrine glands (pit, thryroid)
**More leaky than continuous
*Fenestrated capilarries without diaphragm
**Have windows
**The windows do not have diaphragms that are like a piece of glass in the window
**Found in the renal glomerulus
**More leaky than fenestrated with
*Sinusoidal capilarries
**Bone marrow, liver, lymphod tissue
**Where lots of proteins move in and out of blood
**usually cells can move in and out pretty easily as well.

====Structures====
*Continuous
**Tight jxns with endothelial cells
**Have lots of penocytoic vesicles
***Looks like material is brought into cell from outside
**Not fenestri
**No diaphram
**BM is always present in continuous caps
**Tightest of caps
*Fenestrated with diaphragm
**A little leakier
**Have tight jxns with endothelial cells
**Have some pinocytotic vesicles
**Have fenestri, diaphragm, and bm.
*Fenestrated without diaphragm
**Tight jxns
**Pinocytoics
**Fenestri
**BM
*Sinusoidal
**Some tight jxns, but some of the endothelial cells don't form tight jxns with their neighbor.
**No pinocytoic vesicles
**Have fenestri, without diaphragm
**Discontinuous BM
**Leakiest.

====Image examples====
*Epithelial cells can wrap all the way around a vessel.
*Fenestrations:
**They are arranged in little collections.
*Pinocytotic vessles are much like the fenestra.
**Also called caveoli
**Can fuse to cause little diaphrams
*Diaphragm of fenestra
**Has spokes
**Made of PB1 and other proteins
**PB1 forms fibrilar spokes across the fenestra.

====Facts====
*Entrance to the capillary bed is controlled by the pre-capilarry sphincter.
**controls whether and how much blood flows into the capillary bed.
*Capillaries function to keep cells and protine in the blood.
**BBB exists to
**BBB is made up by continuous capillaries and the cellular barriers on the outside.
*Read 188-189 on function of endothelial cells
**A quesiton will coem from this for exam.

xXVlVc Good post! Found a lot of new and interesting! Will share the link with others:D

===Topics===
*Arteriole-venus anastamosis
**Used them when we played in the snow.
**Blood flow to skin shuts down.
**This is achieved by connecting artery and vein so the capillary bed is bypassed.
**This maintains normal blood flow in arteries and veins.

====Heart====
*has three tunics: endocardium, myocardium, epicardium
**differ in the atrium and ventricle.
*Endocardium:
**Atrium: Endothelium and connective tissue
**Ventricle: Only endothelium
*Myocardium:
**Atrium: Cardiac muscle
**Ventricle: Thick layer of cardiac muscle
*Epicardium:
**Atrium: Connective tissue and mesothelium
**Ventricle: Connective tissue and lots of larger vessels (coronary arteries), and mesothelium.
*Specialized cells:
**Nodal cells
***Set pace of heart
**Perkinje cells
***Modified cardiac muscle cells
***Carry signal from one part of the heart to another.

=====Observation=====
*Endocardium layer of atrium is thicker than the epicardium.
**Makes sense because the atrium may get stretched an endocardium will sustain the structure.
*Epicardium:
**Mesothelium on the outside is often simple squamous epithelium.
*Perkinje cells:
**Looke very diff
**Multiple nuclei and some myofibers
**But not packed full of contractile apparatus

===Lymphatics===
*Lymphatics drain ECF.
**Blood vessels leak
**Lymph vessels recover the fluid that has escaped the blood circulation
**Also impt for lymphatic cells
*Lymphatic capillaries:
**blind ended capillaries
**exist out in tissue
**Have incomplete fenestri
**have very few tight junctions
**have very little bm
**They are super leaky
*The cells of the lymph capillaries are anchored to the connective tissue around them by collagen fibrils.
**So when pressed, they are squished but open up upon freedom from pressure and as connective tissue spreads.
**This pulls fluid into it.
*Caps form larger vessels
**These have thinner walls than veins of similar size.

====Observations====
*Lymphatics sometimes have valves that keep lymph flowing in one direction.
*The walls may not be apparent; they can look like open space with endothelium lining it.

==Lab 6: Cardiovascular tissue==
*There are three layers to cardiac tissue:
**Tunica intima
**Tunica media
**Tunica adventitia
*In some parts of the cardiovascular tissues, one of these three tissues dominates over the others:
**The tunica media is dominant in all arteries (small to large).
**The tunica adventitia is dominant in most if not all veins.
*See Basic Histology 11-7.

===SMALL VESSELS===
*Arterioles and venules are the smallest of the arteries and veins, respectively.
*They are often seen as paired structures in connective tissue.
*Note that the arterioles will have a thick wall composed mostly of tunica media; venules will have a much thinner wall.
*Capillaries are very difficult to see in light microscopy because they are a single endothelial cell thick.
*Note that we use H&E as well as '''orcein''' to stain vessels.
**Orcein generates brown stains.

====Slide 10: Mesentery, human====
*This is an orcein and H&E stain.
*The arterioles and venules are easily seen to be paired.
*Arteriole observations:
**A thin tunica intima exists as a deep, purple, smooth band.
**A thick tunica media clearly distinguishes between arteriole and venule.
**The tunica adventitia is about half as thick as the tunica media and stains as a jagged band of cells.
*Venules
**The tunica intima stains a deep purple as in the arteriole but is not as smooth; each cell seems to jut out into the lumen.
**The tunica media is thinner than in the artiole with a more speckled pattern--less homogenous.
**The tunica abventitia of the venule gives a similar jagged stain but is slightly lighter.
***The two tunica adventitia are often adjacent.

====Slide 25: Lymph node, monkey====
*This is an orcein and H&E stain.
*Similar to slide 10.
*In this section, the venules tunica intima does not show the same jagged pattern as seen in the mesentery.
*Another difference is that in this section the arteriole's tunica adventitia has a definite wavy pattern as opposed to a jagged homogeneity.

====Slide 15: peripheral nerve====
*This is an H&E stain.
*Wavy pattern of arteriole tunica adventitia seen again.

===MUSCULAR (MEDIUM) ARTERIES AND MEDIUM VEINS===
*Medium arteries are also called muscular arteries because of the prominent smooth muscle found in the tunic media.
**However, in muscular arteries, the tunica adventitia is often thicker than the tunic media.
*Muscular arteries also have eleastic fibers running through them.
**These fold over themselves as contraction occurs.
*Some medium arteries show a prominent '''external elastic lamina''' in the tunica media.
*Elastic fibers can also be found running in the tunica adventitia.

====Slide 16: Aorta and mesenteric artery, human====
*This is an orcein and H&E stain.
*The elstic fibers of the tunica media are seen as blue-purple, folded, ghostly, fibers.
*A fairly continuous external elastic lamina can be seen in the transition between tunica media and tunica adventitia.
*Elastic fibers are visible in the tunica adventitia as pink connective tissue.

====Slide 25: Lymph node, monkey====
*This is an H&E stain.
*Elastic fibers of the tunica media are readily seen.

====Slide 10: Mesentery, human====

===ELASTIC (LARGE) ARTERIES===
*Note that this section is specific to arteries.
*We have seen elastic fibers as blue-purple in orcein + H&E; they will appear as read or brown with just orcein.
*In large vessels, ''vasa vasorum'' should be visible in the tunica adventitia

====Slide 16: Aorta====
*This is an orcein stain so elastic fibers will be red / brown.
*There is a definite border between the tunica media and the tunica adventitia.
*Though there is a distinction between the tunica media and the tunic intima, there isn't really a solid border.

====Slide 37: Aorta====
*This is an H&E stain so elastic fibers will be blue-purple.
*Again there is a definite border between tunica media and tunica adventitia but not between the tunica media and tunica intima.

*stopped here

===LARGE VEINS===
*Large veins like the vena cava have longitudinal bundles of muscle cells '''in the adventitia'''.
*Large veins also have thin tunica media.

====Slide 38: Vena cava====
*This is an H&E stain.
*Note that because the vena cava is a large vein, the media is thin and there are smooth muscle cells in the adventitia.
*The vasa vesorum are readily apparent, also.

===THE HEART===

====Atrium====
*The ventricle is easily identified as the tissue with epicardium (which has a high fat content) at the border.
*Note that coronary arteries are also visible, supplying oxygenated blood to the cardiac tissue.

====Ventricle====

=====Slide 19: Heart, ventricle and auricle=====
*Note that the epi, myo, and endo cardium of the atrium and the ventricle are visible.
**The epicardium of the atrium is especially thick.

=====Slide 20: Heart ventricle moneky=====
*In the ventricle, Perkinje fibers are visible but difficult to find.
**These fibers conduct the electricity of the heart.

*stopped here on 01/12/11.

20110110 03 notes.txt

Admin — Wed, 12 Jan 2011 12:39:12 GMT

Admin: moved 20110110 03 notes.txt to 20110110 03 epithelium notes.txt

*started here on 01/10/2011 at 2PM.

==Intro to visual exam==
*They will be in MS326.
*Given via power point.
*Pointer on the slide will indicate what we are supposed to be identifying.
*There will be a multiple choice answer sheet.
*The questions can also be about the object, not just the identity of the object.
*There is about 1 minute per question.
**There are 50 questions per exam.
*There is a review session before the exam.
**Wednesday the 2nd of February.

==Epithelium lecture==

===Objectives===
*Understand the division oftissues into four classes, describing the characteristics of each.
*List the types ofjunctions found between epithelial cells and their unique characteristics. Which ofthese are also found in other tissue types?
*List the surface specializations of epithelial cells and their unique characteristics. Which of these are also found in other tissue types?
*Describe what is meant by epithelial polarity and how apical and basolateral membranes generally differ. Describe how separation oftransporters on an epithelial cell could enable secretion of a substance from the blood into the lumen of an organ.
*Distinguish among merocrine, apocrine, and holocrine modes of secretion. Which is used by serous cells? by mucous cells? by neuroendocrine cells? Can secretion of steroids be said to result from any ofthe three modes of secretion? Explain.
*Describe myoepithelial cells, their function and location.
*Describe the location, composition, and functions of basement membranes. Why is study of basement membranes so interesting with regard to cancer?
*Be able to draw and label all ofthe kinds of epithelia described in Table 4-2 ofyour text.
*Describe the development and classification of glands, as on pp. 76-80 of your text.

===Introduction===
*We classify everything in to four basic tissue groups.
**We've done muscle and nerve.
**Next week is the connective tissue.
*Epithelium is hard to describes but convers many of the functional tissues of the body.
*Epithelium has two general calsses:
**Cells that line a fluid filled space with tissue underneath.
**Chords or ropes of cells
***have lots of blood associated with their surface

===General characteristics===
*Closely spaced cells, not much space in between.
*Adhere closely to one another.
*Form sheets that line cavities or surfaces of organs (or the whole body, like skin).
*Sheet cells are involved in transport of material between compartments.
*These sheeted cells (and even those not in sheets) are polar.

===Epithelial junctions===
*There are terminal bars
**Composed of two EM structures (tight juxns and zonular adherens).
**shows up as a dark staining line at the connection between adjacent, connected, epithelial cells.
**These occur on the basolateral face of the cells.
*The terminal bar is dark between the tight jxns and zonular adheren proteins absorb the stain.

====Tight jxn====
*Tight jxns = zonula occludins
*Think of the old six-packs with plastic rings and where the ring held the cans (cells) together.
*Recall that these tight jxns are only visible on EM.
*Looks like a quilting in metal-shadowed freez-fracture EM.
*Tight jxns are very complicated.
*These effectively block the passage of fluid between adjacent cells.
*The tight jxns has two functions:
**as a fence: proteins on the basolateral side of the cell cannot pass onto the apical side and ''vice versa''.
**as a gate: can allow ions or molecules through,
***Depends on their selectivity, the signaling state of the epithelium, etc.
***Epithelium can be signaled to open their tight jxns to certain molecules.
*There are several protein components:
**ZO1 and ZO2 (zonulin occludin)
**Claudin
**Occludin
*These are important in structure and regulation.

===The belt desomosome===
*Called a desomosome because it looks a bit like a spot desomosome but is really different.
*At the top of the cell, below the zonula occludin.
*The zonula adheren is an important part of connecting the two cells and integrating the cytoskeletons, especially the terminal web.

===Maculla adherens===
*Not just epithelium but many cells have macula adherens.
*These are like spot welds between cells.
*Macula = spot
**Immacula = spotless
What's the difference between a macula densa and a desomosome?

*At the desomsoem, there is a plaque of prteoins in either cytoplasm, there are membraneous proteins and there are proteins that bridge between the two cells
**This is an important part of the strength of the skin surface.

===Hemi-desmosome===
*Half of a desomsome.
*These occur ont he base of the cells, to connect them to ECM (connective tissue).
*They have a plaque of cells in the cytoplasm, membraneous proteins.

*Intermediate filaments are important for hemi and full desomsoems.
**These are made of keratin.

*There is a large network of actin filaments called the terminal web.
**The actin filaments from the network can rup apically to generate the microvilli
**When we look at cancers, we sometimes look at their intermediate filaments; if they are made of keratins we usually call the tumor a carcinoma.

===Gap jxn===
*A connection between neighboring cells.
*Not a strong physical connection.
*Important functional connection.
*Membranes are head together with a fixed, narrow gap.
*Freeze fracture will help us see this.
*There are pores between one cell and it's neighbor allowing small molecules to pass through.
*Connexons make up these pores.
*One connexon from each cell alighn their channels to form a pore.
**There are many of these per gap jxn.
*The pore size is less than 1500 MW so signaling molecules like cAMP can get through but things like proteins cannot.
*Gap jxns are regulated in most cells by cytoplasmic Ca+ levels.
**If one cell gets injured, the ca+ rises and the neighbors shut their gap jxns so they don't get injured, too.
**It's the connexons that close.
*The connexon is the name of the structure, the protein is a connexin.

===Cells specializations===
*Microvilli are found on most cells of the lumen of the gut.
**They can generate a brush border if long enough and packed close enough.
**We also called them striated borders.
*The glycocalyx is sugar residues hainging off of glycoproteins and glycolipds of the cells.
**Can be stained by puriotic reactive sschiff reagent.
**made by actin
*Microplicae
**These are ridges that come up off the cell.
**Only seen via EM.
**Made by actin
*Steriocilia
**Made by actin
**Giatn microvili
**Called cilia because they can be seen individually with LM.
**There are steriocilia in the kidney and hair cells.
*Basal foldings
**"highly amnplified" basolateral surface means that there are lots of foldings to increase the surface area.
*Cilia and flagella
**Cilia are at the surface of epithelial structures.
**Flagella are generally singular.
**These have Microtubules to make up the axonea.
**This is a complex structure with many proteins.
**Genetic diseases in any of these proteins can cause defective cilia.
**We generally are thinking of '''motile cilia''' when we think of cilia.
**There are also '''primary cilia'''.
***These are important for epithelia cilia.
***These can be important for sensing the throw through the tubule, even, like in the kidney.

===Epithelial polarity===
*The apex is the part that faces the lumen or outside.
**AKA lumenal membrane
**AKA mucosal membrane
*Other side is the basolateral membrane
**AKA serosal membrane--closest to the serum or blood
**AKA Abluminal membrane.

===Secretion===
*Epithelial secretion:
**This is ambiguous.
**Often means from the blood side to the lumen; like absorption means from lumen to blood.
**More general is just release from the cell.
**In a glandular context: secretion means into lumen or blood, or ... not specific.
*Glandular secretion occurs in three ways:
**Merocrine: what we usually think of
***Material iin the cell, in a vesicle, which gets merged with the plasma membrane, material is released.
***Secretion of a product that is packaged int he cell.
***Hard to do this with things like fats.
**Apocrine:
***Move fat covered in proteoins to the inner membrane then wrap it in a very small amoutn of membrane and dump it into the ECF.
***This happens in arm pit and groin sweat glands; this gives us our special odor.
**Holocrine:
***When the entire epithelial cell is sloughed off to provide the secretion.
*Secretion can be constitutive or regulated.
**For example albumin is secreted constitutively.

====Protien secretion====
*There are two types of protein secretion:
**Serious cells:
***Cytoplasm stains well with H+E
***Ex: salivary gland
***Proteins being released in a watery fluid
***This is mericrine section.
**Neuroendocrine cells:
***Scattered throughout epithelia
***Have secretory granules on the blood side.
***This is mericrine section.

====Mucous secrtion====
*A special type of protein secretion.
*The proteins are covered withs ugars.
*Goblet cells are usually by themselves.
**CAlled this because the mucins get packaged together at the top (apical) of the cell and make it look like a goblet.
*Mucin is the protein.
**it has lots of sugars.
**sugars make it stay hydrated well
*In neuroendocrine cells we can concentrate the proteins in the vesicle into a small bundle.
**Mucin won't do this because it needs so much water.
*Also, mucin secreting cells won't stain well with H+E.
*Goblet cells have lots of ER
*They assume we know about the txn and txln and packaging of protines for secretion.

====Steroid secretion====
*STeoird are produced in special epithelial cells.
*Not packaged for secretion because it can pass through membranes.
*They can hardly hold the steroid in; perhaps by protein steric binding.
*These cells have ltos of:
**sER
**mt
***have shelf-like cristae instead of tube like cristae
**fat droplets (a precursor for many steroids)
Something here to study on our own.

===Basement membrane===
*The old literature calls basement membrane the basal lamina.
*This is an extra cellular structure.
*Has a lamina densa and one or two lamina rara (lamina lucida)
**Remnantas of dehydration.
**Used in pathoglogy to distinguish between disease states, especially in the kidney.
**Two if both cell layers adjacent to the bm are epithelial.
*Lamina reticularis:
**Set of fibrilar protins connected to the bm.
**not officially part of the bm.
*Basement membrane is at the basal surfave of most epithelial cells.
**Most neurve cells and msucle cells have their own bm.
*BM formed by type 4 collagen.
**This type does not form fibrils.
**Produces a felt-like structure in bm.
***Felt is a fabric that is made by gluing small fibers together, essentially. It is not woven like cotton.
*There are lots of glycoproteins in bm:
**laminin
***very large
*proteoglycans, too
**
*These molecules are really big.

====BM fxn====
*BM is an anchoring substrate for the epithelium.
**Some blistering disease states are from poor anchoring of skin epithelium to the bm.
*BM is a Signal template for differentiation
**Interfaces with regenerating cells to tell them what kind of cell to be and when and where to grow.
*BM is a filter for molecules
**Like in the kidney, removing proteins from filtrate.
*BM is a "filter" for cells
**it keeps cells where they are supposed to be.
**Most epithelial cells cannot get up and move (diapedesis), unless they have been altered, like in cancer.

===Epithelium types===
*We should be able to classify epithelium types and glands.
*Epithelium is named by shape of the cells at the surface:
**Squamous: flat like fried egg
***Often so flat that we cannot see cytoplasm in LM.
**Columnar: tall
**Cuboidal: like a cube
*Simple: one layer of cells
*Stratified epithelium have more than one layer of cells.
**Still named by cells at the surface.
**Most common is stratified squamous epithelium, which have fried eggs at the top but columnar at the bottom.
*Transitional epithelium
**Lines urinary passages, especially bladder.
**Armor plated cells at the surface (really acidic urine)
**Can withstand lots of stretch as a group
**Has "umbrella" cells at the surface that aren't quite cuboidal.
*Pseudostratified colunnar epithelium
**line ?
**have a jumble of nuclei
**All cells touch the bm, so it is falsly stratified.

==Laboratory 4: Epithelium==

===TYPES OF EPITHELIUM===
*Epithelial cells that form sheets are best viewed when the section is perpendicular to the plane of the epithelial sheet, so you will have to pay careful attention to the plane of section in each specimen.

====Simple sguamous epithelium====
*Cytoplasm is very thin and may not be visible.
*The nuclei may be flattened or rounded.

=====Slides 91 and 88: Bowman's capsule=====
*The bowman's capsule is a classic example of a squamous '''epithelium'''.
*The outer layer of the kidney is the cortex.
*Renal corpuscles are scattered throughout the kidney.
**The corpuscle looks like an empty space with a hemorrhage of cells filling it.
**The simple squamous epithelial cells surround the empty space.
*See Wheater, Fig. 16.6-16.17).
*The nuclei of the simple squamous epithelial cells are often close together.
**Though, often squamous cells are wide and therefore the nuclei are far apart.

*We can also find '''endothelium''' in slide 91.
**This is found lining the blood vessels of the kidney.
**Often the nucleus will be visible but all the cytoplasm will not.

*The last -elium is the mesothelium which is found on the outside of organs that face a space in the body, like the outside of the small intestine or the liver.
**We'll see the mesothelium when we look at cardiac tissue.
**Can be seen on slides 19, 54, and 10.
What is mesothelioma

====Simple cuboidal epithelium====

=====Slides 91 and 88=====
*Simple cuboidal epithelium make up most of the tubes in the kidney.
*These cells are nearly as tall as they are wide.
*The nucleus of simple cuboidal epithelium are slightly flattened or fully round.
*The cytoplasm is generally easily seen.
*These are informally called "high" or "low" if they are slightly tall or slightly wide.

=====Slide 87: Thyroid=====
*This slide of the thyroid has lots of cuboidal simple epithelium.
*The thyroid has follicles that are filled with colloid (a mixture with properties between those of a solution and fine suspension per wordnet).
*As colloid accumulates in the follicles, surrounding epithelial cells can be compressed.

====Simple columnar epithelium====
*Simple columnar epithelium are much taller than they are wide.
*The nuclei often elongate along the long axis in order to fit in the cell.

=====Slide 58: jejunum of monkey=====
*Note that the brush border can be seen as a sometimes-fuzzy-sometimes-defined layer on the apical surface of the columnar simple epithelial cells.
**It sometimes even looks like a cell membrane, with darker areas with a lighter middle--like longitudinal stripes.
**Compare with electron micrographs in Wheater (Fig. 14.25a&b) and
Basic Histology (Figs. 15-25, 15-28, 15-29).
*Note the goblet cells scattered individually in this epithelium.
Can you see a basement membrane? (probably not)

=====Slide 63: gallbladder=====
*Note that there is no goblet cells in the gallbladder as there are in the jejunum.
*Also, there is very little fuzziness or longitudinal striation because the microvilli are much smaller than in the jejunum.
**Note that mucus adhering to the apical surface of the gallbladder cells can look a bit like microvilli.

====Pseudostratified (ciliated) columnar epithelium====

=====Slide 48: Trachea=====
*This is the trachea.
*There are cilia present here in order to move mucus up the airway with trapped pathogen.
*Note that the mucins of the treacheal goblet cells stain more readily than those of the small intestine.
**Therefore, instead of appearing as a complete lack of stain, they give a granular, light pink-to-blue color.
*The basement membrane is clearly visible in the trachea as a thick pink band.
*Recall that pseudostratified columnar epithelium is not stratified because all the cells reach the basement membrane.
*Recall that basal cells are those epithelial cells that are the closest to the basement membrane.

====Stratified squamous epithelium====
*Stratifed squamous epithelium come in two flavors: keratinized and unkeratinized.
*In keratinized cells, the amount of keratinization will generally increase as the cells reach the lumem and this can change the appearance.
**They become lighter stained, wider, and have fewer and fewer nuclei.
*'''Note that to correctly identify stratified squamous epithelium, one must clarify wehther it is keratinized or non-keratinized'''.
**Keratinization seems to give the cell morphology a very irregular shape, to cause light staining, and to be associated with very few nuclei.
**The esophagus (non-keratinized) has a much more regular, flat shape, has many nuclei and still stains pretty well.

=====Slide 48: Esophagus=====
*The esophagus provides a good example of a non-keratinized stratified squamous cells.

=====Slide 30: Skin=====
*Here we see the layers of skin.
*Highly keratinized upper layers may be missing as it is hard to section them because they are so tough.

====Stratified cuboidal and columnar epithelium====
*We will see examples of cuboidal and columna stratified epithelium later.
*For now, examine these in Fig. 5.8 in Wheater.

====Transitional epithelium====

=====Slide 69: Urinary bladder=====
*The bladder is a good example of transitional epithelium whcih makes sense as it needs to be able to be very compact or very very distended.
**Transitional epithelium is known for its ability to stretch.
*The surface-lining cells are often called '''umbrella''' cells.
*The umbrella shapes give the greatest difference between distended and compact.
**In the distended state, the cells form a smooth layer with few bumps.
**In the compact state, the umbrella cells form baking-cookie shapes lying next to one another.
*Another difference in the distended and compact state is the concentratin of nuclei near the bm: lower density in the distended state.

====Epithelial transitions====
*Where two different types of epithelia meet, the tissue is often weak.
**This is often the site of lymphocyte accumulation.

=====Slide 81: Cervix=====
*The cervix has stratified squamous non-keratinizing (as we saw in the esophagus) and simple columnar cells.
**Note that there is also the endothelial cells of the blood vessels.
**Compare to Wheater 19.23.

===GLANDS===
*We will study glands more closely in each organ system.
*This lab will introduce us to glands.
*We should know the major classifications of glands as described in Basic Histology, Chapter 4, pages 77-79.
**These classes have, in part, to do with the ductal construction of the gland.
*It is hard to characterize the class of a gland by any single slide, so we will not be expected to classify glands based on their ductal architecture.
*All exocrine glands are considered complex.

*Gland objectives:
**At the completion of this portion of the lab you should be able to:
***distinguish between ducts and secretory units,
***distinguish between tubular and acinar secretory units, and
***distinguish between serous and mucous secretory cells

====Unicellular glands====
*Unicellular glands are individual cells scattered throughout a tissue.
*Unicellular glands have no duct at all.
*Examples include goblet cells, ween in slide 58 (small intestine) and slide 48 (epithelium of the trachea).
**Recall that the small intestine was a simple columnar epithelium and the trachea was a pseudostratified columnar epithelium.
Why does it make sense that the trachea is pseudostratified?
What's the special function of a pseudostratified epithelium?

====Multicellular glands====
*Multicellular glands have...multiple cells combining to form the gland.
*Only the very simplest multicellular glands lack ducts; most have some sort of epithelium-lined duct.
*There are two categories of multicelluarl glands:
**Simple: which have a single duct that is unbranched.
**Compound: which have a branched ductal system.
***All major exocrine glands have compound duct structures, but this can be hard to see in histological slides.

=====Exocrine glands=====
*The secretory unit of exocrine glands can be described as:
**elongated or tubular
**rounded or acinar.

====Slide 45: submandibular gland====
*In this slide we can see both serous and mucous cells.
**Serous cells are basophilic and therefore stain with eosin and are a deep pink.
**Mucous cells stain faintly
*Serous cells produce a watery, protein-rich secretion.
*Mucous cells produce glycoprotein-rich secretions.
*The submandibular gland is considerd compound, so it will have branched ducts.
*The gland is also considered tubuloacinar so it demonstrates both elongated ducts and rounded dcuts.
*The submandibular gland is also called '''mixed''' gland because it has both serous and mucosal secretion function.
*As the ducts proceed from small to large, they will shift from simple cuboidal to stratified cuboidal and then stratified columnar.
**Small ducts = simple cuboidal.
**Large ducts = stratified columnar.
I couldn't see this phenomenon.
*One can differentiate between the serous cells and the mucous cells by the way they stain with H&E:
**Serous cells stain blue / reddish-purple.
**Mucous cell are unstained.
**This makes sense because mucous cells will be generating vesicles full of glycoprotieins that won't stain well with H&E.
**On the other hand, mucous cell stain well with PAS.
***PAS = Periodic acid-Schiff stain
***Turns carbohydrates a deep magenta.
***It makes sense that mucous cells would be stained with this because they are secreting '''glyco'''proteins.

*Note that we will be expected to know which type of secretion is used by each gland we study.
*There are 3 types of secretion:
**merocrine: no loss of cytoplasm, vesicle fuses with membrane
**apocrine: some loss of cytoplasm
**holocrine: entire cell is shed
*One cannot determine the method of release through light microscopy.
*In the '''submandibular gland, both the mucosal and serous cells''' release their contents (glycoprotiens and watery protein, respectively) in a '''merocrine''' fashion.

====Endocrine glands====
*While exocrine glands release their contents via duct onto an epithelial surface (think pancreas into the duodenum), endocrine glands secrete their production into the blood.
*No ducts are necessary when secreting into the blood.

=====Slide 89: Adrenal gland=====
*Notice that the adrenal gland, which secretes hormones directly into the blood, has now duct system.
*Notice the numerous small blood vessels that pass through the structure.

===SPECIALIZED EPITHELIAL STRUCTURES===

====Basement Membrane====
*The basement membrane is composed of glycoprotiens.
*Therefore, like mucous secreting cells, it stains deep magenta with PAS (periodic acid-Schiff stain).
*Note that the basement membrane is usually not visible with H&E stain because of light staining and the very thin nature of the basement membrane.

====Cell surface specializations====
*One should be able to distinguish between cilia and microvilli.
**Slide 48, the trachea, shows cilia--long, individual fibers coming of in wavy patterns.
**Slides 58 and 63 (jejunum and gallbladder) demonstrate microvilli as a fine, soft, haze of stain around the cells.

*stopped here on 01/10/2011

Flashcards.txt

149.166.42.231 — Sat, 08 Jan 2011 17:01:31 GMT

24.15.60.132:

red stain; eosin

blue stain; hematoxylin

number of nuclei in skeletal muscle; many

location of skeletal muscle nuclei; periphery

name of a full length muscle cell contractile organelle; myofibril

sarc in greek; flesh

diameter of human RBC; 7-8 microns

thickness of lm sections; 5-7 microns

do skeletal muscle cells have a basement membrane?; yes

where is the skeletal muscle basement membrane?; on the outside of the sarcolemma

fasicles are a group of...; myofibers

individual muscle cells are held together by the; endomyesium

this layer runs into and throughout a fascicle; perimyseium

this is the outer-most layer of a fasicle; epimyseium

I bands occur where in the sarcomere; where there are not thick filaments

do I bands change orientation of light?; no

define the A band; where thick filaments exist

do A bands change orientation of light?; yes

what happens at the z line?; thin filaments attach to their backbone

at what line do thick filaments attach?; M line

define the H zone; where there is only thick filaments without thin filament overlap, centered around the m line

thin filaments made of actin or myosin?; actin

thick filaments made of actin or myosin?; myosin

where is the atpase unit of myosin; the head

what ion must be elevated to allow cross-bridge formation? to what concentration?; Ca, 1 mM

true or false: ADP and Pi are released upon ATP burning by myosin; false

what are the three domains of troponin and what do they do; C (senses Ca), I (inhibitory, binds actin), and T (interacts with tropomyosin)

this protein of the thin filament inhibits myosin from binding actin; tropomyosin

what two proteins binding causes myosin to release Pi?; myosin to actin

ADP release from myosin is triggered by what event?; the first 45 degree rotation of myosin on actin

troponinC binds calcium allowing this protein to move; tropomyosin

how far does tropomyosin move around actin to allow myosin binding?; about 5 minutes on a clock face (30 degrees)

t tubules are made of what; cell membrane

t tubules reach into the cell and touch what?; sarcoplasmic reticulum cisternae

what is a triad?; the junction of two terminal cisternae with a T tuble at the A-zone / I-zone junction

describe the a-zone / i-zone junction; the a zone is where there is no thick filament and the i zone is where there are only thick filaments so the junction is the end of the thick filament

does the basemement membrane outside the sarcolemma invaginate with the T tubule?; yes, a little

what is the difference between triads in mammals and other animals?; other animals have a triad in which the T tubule touches the sarcomere at the Z line

the nerve plate is a synonyme for the...; synapse

how many muscle fibers can one axon innervate?; one or many

define a motor unit; a neuron and all the muscles it innervates

can a neuron fire only a portion of it's motor unit?; no, it is all or nothing

in the eye, would you predict a large or small number of myofibers for each motor unit?; small because the eye requires very fine movement

which striated muscle type has branched myofibers?; cardiac

skeletal myofibers are joined physically, electrically, or both?; physically

cardiac myofibers are joined physically, electrically, or both?; physically, electrically

location of cardiac nuclei; centrally located

number of cardiac nuclei; 1 or 2

does cardiac or skeletal muscle have more vascularization?; cardiac

name the junctions found in an intercalated disk?; facial adherens, macula adherens, gap junctions

facial adherens are like what type of junction; zonula adherens

macula adherens are like what type of junction; desmosomes

what happens at each of the three junctions of the intercalated disk?; thin filaments connect at the facial adherens, thick filaments at the macula adherens, and electrical signals connect at the gap junctions

do gap junctions hold cells physically together?; no because they don't affect cytoskeleton

where along the myofiber are gap junctions located?; along the longitudinal membrane

the atria of the heart can release what hormone? what is its function?; atrial naturetic peptid, vasodilator, diuretic (water and Na loss at kidney)

diads are found in this type of muscle; cardiac

this type of muscle is spindle shaped; smooth muscle

location and number of smooth muscle nuclei; central, single

describe a smooth muscle cross-section in terms of cell diameter; there will be a variety of diameters because some cells will be cut toward their ends where they are tapered and some will be cut at the middle where they have a larger diameter

this muscle type does not have sarcomeres; smooth muscle

to what type of cytoskeletal fiber are actin and myosin attached in smooth muslce cells?; intermediate filaments

desmin and vimentin make up what type of cytoskeletal fiber?; intermediate filament

intermediate filaments are made of what two proteins?; desmin and vimentin

dense bodies connect what?; thin filaments of actin and intermediate filaments

membrane dense bodies connect what? thin filaments of actin and intermediate filaments

what two structures link thin and intermediate filaments?; dense bodies and membrane dense bodies

these structures of smooth muscle generate dark bodies on the membrane and cytoplasm; membrane dense bodies and dense bodies

this muscle type doesn't require T tubles; smooth muscle cells

this muscle type may use the state of intermediate filaments to regulate contraction

smooth muscle uses what cue to cause myosin to assemble into filaments?; phosphorylation of myosin

in smooth muscle, phosphorylation of myosin causes what?; myosin to form filaments

for smooth muscle contraction, must myosin be phosed or dephosed? phosphorylated

which muscle type may generate a corkscrewed nucleus upon contraction?; smooth muscle

which muscle types have gap junctions?; cardiac and smooth

what facilitates "unitary smooth muscle" activity?; electrical connectivity via gap junctions

multi-unit smooth muscle is controlled by gap junctions, neuronal stimulation, or both; neuronal stimulation, mostly

what cell is capable of regenerating skeletal muscle?; satellite cells

where to satellite cells live?; just below basement membrane next to skeletal cells

in a light microscope slide, what does a satellite cell look like?; a peripheral nucleus or a fibroblast

can smooth muscle regenerate?; yes, most smooth muscle cells can dedifferentiate and replicate

what are the steps in satellite cell regeneration of skeletal muscle (5)?; satellite cells -> myoblasts -> myotubles -> myofibrillogenesis -> myofiber

describe myofibrillogenesis (4 things) (one step in the regen of skeletal muscle); formation of myofibrils of myotubes, nuclei pushed outward, fusion, elongation

describe a myotubule (one step in the regen of skeletal muscle); long cells, multiple cells bound together

describe myoblasts; can fuse, don't look like muscle but do have similar expression pattern

describe myotubes; a syncitium of myoblasts

does hematoxylin bind acidic or basic particles?; acidic

is hematoxylin acidic or basic?; basic

H&E stands for...; hematoxylin and eosin

with what two elements does hematoxylin react to generate it's color?; Aluminum or iron

hematoxylin generates what color?; blue

what color does eosin generate?; red

does eosin stain acidic or basic particles?; acidic

chromatin and ribosomes are stained by what stain?; hemotoxylin

connective tissue, cytoplasm, collagen, muscle fibers, and mt. are stained by; eosin

connective tissue, cytoplasm, collagen, muscle fibers, and mt. are turned red by this stain; eosin

vacant areas on slides may have contained this type of tissue, dissolved during fixation; adipose

size of RBCs (in a slide and in real life); 7 micrometers, 10 micrometers

what type of muscle can be found in the uterus, appendix, bladder?; smooth

in the GI tract, what are the orientations of the inner and outer layers of smooth muscle?; circumferential and longitudinal

this organ has "interlaced" smooth muscle; uterus

this organ has disparate bundles of smooth muslce separated by connective tissue; bladder

what is the difference between the smooth muscle of the uterus and bladder?; bladder muscle is disparate while uterus muscle is interlaced

what color (and by which stain) does connective tissue stain?; red via eosin

the soft palate and tongue are made of what type of muscle?; skeletal

myofibers are surrounded by what layer?; endomyseium

perimysium surrounds what unit?; bundles

epimyseium surrounds what unit of muscle?; fasicle or gross muscle unit

the cns is composed of these two structures; brain, spinal cord

grey matter of the brain exists in two forms; surrounding white matter and as nuclei in the brain

this type of "matter" forms neural tracks of the CNS; white

the PNS is composed of these two structures; ganglia and nerves

define ganglia; clister of neuronal cell bodies.

sensory fibers are efferent or afferent?; afferent

motor fibers are efferent or afferent?; efferent

name the three types of neurons based on function; excitatory, inhibitory, and modulatory

name the three types of neurons based on processes; multipolar (have many processes), bipolar (have two processes), and pseudounipolar (rare)

name three ways neurons can be classified; function, NT, number of processes

name three NTs: gluatmic acid, GABA, NE

give two synonyms for the neuron cell body; perikaryon, soma

this cell type has a prominent nucleolus; neuron

what is a nissl body?; stained rER

the rER of neurons shows up as this named structure; nissl body

this pigment stains the lyposome; lipofuscins

mt of neurons have this particular shape; cucumber

true or false: primary dendrites branch into smaller dendrites?; true

small dendrites are called...; spines

there are two types of dendrites depending on their direction; apical and basal

this type of dendrite faces away from the cortex of the brain; apical

basal dendrites face which direction?; toward the cortex

spines of neurons have what anatomical features; head and neck

what is the function of spines?; to allow synapsing with neighboring neurons

how many axons are there per neuron?; one

the axon hillock is begun by this named structure; the initial segment

do collaterals or terminal come off the axon first?; collaterals

the axon hillock is especially dense with this cytoskeletal structure and an organelle...; microtubules and mitocondria

"fast" transport along the axon moves at what approximate rate?; several hundred mm / day

"slow" transport along the axon moves at what approximate rate?; a few mm / day

which motor moves material from the body of a neuron down the axon?; kinesin

dynein moves material toward...; the soma (retrograde)

there are two types of neuronal synapses: electrical, chemical

are chemical or electrical synapses more common in mammals?; chemical

what structure facilitates electrical synapse?; gap junctions

which is faster, a chemical or electrical synapse?; electrical

what are the three components to a chemical neuronal synapse?; presynaptic cell, synaptic cleft, and postsynaptic cell

can any part of a neuron perform as the post-synaptic area?; yes (dendrite, soma, axon, spine)

describe three dynamic aspects of spines; length, location, and number of branches

name the glial cells of the CNA and PNS; oligodendorcytes and schwann cells

what type of cells produce myelin sheaths?; schwann cells in the PNS

myelin is a protein with what type of modification?; addition of lipids--a lipoprotein

how many (and what type of) cells produce the insulation between two nodes of ranvier?; one oligodendrocyte, a schwann cell

in the PNS or CNS does a single glial cell wrap around many axons?; PNS

what color is myelin in an EM?; dark, black

what protein is important for guiding a regenerating neuron?; myelin

how does "bridnging" work to regenerate neurons?; bridging uses a tube full of schwann cells to generate myelin to help a neuron grow in the right direction when regeneratin

this type of cell is the most numerous cell in the CNS; astrocyte

name the two types of astrocytes; fibrous, protoplasmic

which type of astrocyte (fibrous or protoplasmic) is found in grey matter?; protoplasmic

an astrocyte with a long, thin processes would be considered what type of astrocyte?; fibrous

name four functions of astrocytes; physically support neurons, maintain homeostasis, release neurotrophic factors, help transduce signal (?)

astrocytes are able to connect with epithelium through this structure; "end feet"

are astrocytes found on the periphery or in the cortex of the CNS?; periphery

how do astrocytes and neurons interact?; through spines (from either of them)

this cell type is increased after the brain suffers ischemia; astrocytes

name the four components of the blood brain barrier; endothelial cells, basement membrane, astrocytes' end feet, pericytes

endothelial cells of the blood brain barrier use this type of juction to keep even ions from passing; occluded junction

occluded junctions are found in this barrier; blood brain barrier

a macrophage of the CNS has this name; microglia

microglia arise from this tissue; bone marrow

IL4 turns on this immune cell of the CNS; microglia

microglia can be activated this cytokine; IL4

of neurons, astrocytes, and microglia, which are smallest?; microglia

microglia are indicated as culprits in what neurodegenerative disease?; MS, they chew up myelin

what causes the relapsing-remitting course of MS?; multiple exposure to pathogens that activate microglia

are abs generated in MS?; yes, against myelin

ependymal cells line what (in the CNS); central canal of spinal cord

what type of cells are ependymal cells; celiated, cuboidal epithelium

does white or grey matter form the horns of the spinal cord?; grey

what type of cells are found in the ventral horn?; motor neurons

sensory neurons are found in this horn of the spinal cord; dorsal

any part of the spinal cord that does not contain cells is called; neurophil

what part of the spinal cord contains white matter?; ascending and descending tracts

what are the two types of ganglia of the PNS?; sensory, autonomic

name the two locations of sensory ganglia; cranial and dorsal root

name the two locations of autonomic ganglia; sympathetic chain, intramural

what type of cells are associated with sensory ganglia and autonomic ganglia?; pseudounipolar / satellite cells, multipolar / satellite cells

a single neuron has what layer wrapped around it?; endoneurium

several neurons are bound by the...; perineurium

this layer covers a nerve bundle; epineurium

name the major types (and subtypes) of nerves; somatic (sensory and motor) and visceral (sensory and motor)

at the dorsal root ganglia, what type (somatic or visceral) and subtype (sensory or motor) of nerve would you expect to find?; somatic AND visceral, sensory

this type-subtype of nerve is very precise as to where came it's signal; somatic, somatic AND motor

among the somatic nerves, which subtype (motor, sensory) is faster?; motor

this type of nerve controls smooth muscle, glands, cardiac rhythm, and body homeostasis; visceral nerves

signal from visceral, sensory nerves generally come from...; internal organs

which type of sensory nerve is vague in it's location (somatic or visceral)?; visceral

at what location in the spinal cord can visceral sensory stimulation get confused as somatic sensory?; the dorsal horn

what NT is used at the sympathetic ganglia?; ach

what is a "division" synonym for the sympathetic division?; thoracodorsal division

are preganglionic visceral motor neurons short or long?; short (because they are sympathetic)

which division provides "awareness and survival" and which type and subtype of neurons are being used?; sympathetic, visceral, motor

what is a "division" synonym for the parasympathetic division?; craniosacral division

this system has long pre-ganglionic neurons; parasympathetic

this chemical conserves lipids in sections; osmium tetroxide

what color do lipids turn when treated with osmium tetroxide?; black or brown

what color does osmium tetroxide turn myelin? why?; brown, becuase it is a lipo-protein

of the epineurium, perineurium, and endoneurium, which is coursest?; epineurium (perinuerium is more wavy and less collagenous)

what color does endoneurium stain (H&E)?; pink

this stain makes connective tissue a blue-green; Masson's trichrome

masson's trichrome turns what tissue blue-green?; connective tissue

nuclei are turned purple by this stain; Masson's trichrome

myelin is turned what color by Masson's trichrome?; blotchy white

what shape / color would you expect the nucleus of schwann cell to be in a Masson's trichrome stain of a peripheral nerve?; arched (folded around nerve), purple

to which division are unmyelinated PNS nerves likely to belong? why?; parasympathetic, because the signals sent usually don't have to happen fast

rER is called a "nissl" body when stained with this stain; nissl stain

what color is a nissl body? what structure generates the nissl body?; deep blue; rER

what cell type is found in the ventral horn? what type of neuron is it?; visceral motor neuron, multipolar

what neuron stains well with Nissl? where is this cell type located?; visceral motor neurons, ventral horn of the spinal cord

do multipolar neurons have multiple axons?; no

how does one identify the axon of a multipolar neuron?; the only process with an axon hillock which will stain lighter than the rest of the process because it has lots of MTs but little rER and little mt

what type and subtype of neuron bodies reside in the lateral horn?; visceral motor (autonomic)

this type of neuron gives off one process that quickly splits into two; pseudounipolar

this type of neuron is pseudounipolar and found where; sensory, dorsal root ganglia

large nuclei, lots of euchromatin, and prominent nucleoli are signs of...; high metabolic activity

somatic and visceral motor neurons are of this type (processes); multipolar

these types of cells surround neuron cell bodies in the sympathetic chain; satellite cells

this tissue type comes either as cells that line fluid filled spaces or as chords ropes; epithelium

what tissue type is known to line cavities or surfaces of organs?; epithelium

this general tissue type forms sheets of cells that work to transport material between compartments; epithelium

terminal bars are composed of what two structures?; tight junctions and zonular adherens

on the basolateral surface between two epithelial cells one may see a dark stain representing this structure; terminal bar

tight junctions are also known as ...; zonula occludins

describe the two functions of the tight junctions of epithelial cells; keep proteins in their compartment (apical or basolateral), keep ions or molecules from crossing the epithelial barrier

describe the selectivity of an epithelial tight junctions; how much the cell will let pass between epithelial cells

name the four proteins important to tight junctions; ZO1, ZO2, Claudin, and occludin

what two proteins make up zonulin occludins?; ZO1, ZO2

Claudin, occludin, ZO1, and ZO2 form what structure?; tight junction

what is the synonym for belt desomsosomes?; zonula adheren

are zonula occludens or the belt desmosomes more apical on epithelial cells?; zonula occludens

belt desmosomes connect what?; the cytoskeletons of neighboring cells, especially the terminal web.

these are considered "spot welds"; macula adherens

at this connecting structure, there is a "plaque" of proteins and cytoskeletal elements; desmosomes, hemi-desmosomes

these connecting structures are important to the strength of skin; desmosomses

this connecting structure is found at the basal aspect of epithelial cells; hemi-desmosomes

hemi-desmosomes connect what?; epithelial cells and the ECM (connective tissue or basement membrane)

this protein makes intermediate filaments; keratin

this type of filament is associated with hemi and full desmosomes; intermediate filaments

what type of filament makes up the terminal web?; actin

actin filaments from this structure generate microvilli; the terminal web

microvilli are made by this type of filament; actin

cancers are sometimes classified by this cellular component; actin filaments

when a cancer has actin filaments made of keratin we call it what type of cancer?; carcinoma

each cell contributes many of these to form a gap jxn; connexon

protein that forms gap jxns; connexins

size of gap jxn poor (in molecular weight); 1500 MW

ion that regulates opening and closing of gap jxns; Ca

gap jxn in the case of cellular injury? why?; close, because damaged cell releases Ca which causes connexons to close

a "brush border" is what?; a long duration of microvilli

striated borders of epithelial cells are also called...; brush borders

define the glycocalyx"; sugar residues hanging off of glycoproteins and glycolipids of the cell membrane

this reagent stains the glycocalyx; puriotic reactive schiff reagent

these are ridges that rise up off of epithelial cells; microplicae

microplicae are what and made by what?; ridges rising out of epithelial cells, made by actin

name three epitheilial surface specializations made by actin; microvilli, microplicae, steriocilia

these are giant microvilli; steriocilia

location of steriocilia; kidneys and hair cells

what is the purpose of basal foldings?; to increase surface area

cilia are composed of what type of filament?; microtubules

this epithelial specialization is useful for sensing flow; cilia

difference between cilia and flagella?; flagella is usually singular

the axoneme is part of what specialization? what type of cells have these?; cilia / flagella, epithelial cells

describe the arrangement of motile cilia and primary cilia; 9+2, 9+0

name five epithelial cell surface specializations; cilia / flagella, steriocilia, microvilli, basal folds, microplicae

name the two sides of an epithelial cell and their synonyms; apical (lumenal, mucosal) and basal (serosal, abluminal)

describe the three types of secretion?; merocrine (vesicles), apocrine (dump some membrane into ECF), holocrine (whole cell released)

describe apocrine secretion (mechanism, location, contents); dumps some of it's own membrane into the ECF, sweat glands of groin and armpits, generally fat and protein

name two types of cells that secrete proteins; serous cells, neuroendocrine cells

which type of cells secrete protein in a watery fluid? give an example; serous cells, salivary glands

what type of secretion do neuroendocrine cells use? into what do they secrete?; merocrine, blood

give an example of a mucous secreting cell; goblet cells

what type of molecules make up mucous?; proteins (mucin) covered with sugars

how does sugar modification affect mucins of mucous secreting cells versus neuroendocrine cells which also secrete protein?; the mucous proteins cannot be concentrated as much because they require water (osmolarly)

steroid synthesizing epithelial cells have lots of...; sER, mt, shelf-like cristae, fat droplets

what type of epithelial cell is found in the sweat gland, mammary gland, lacrimal gland, and salivary gland?; myepithelial cell

myoepithelial cells are found between what two layers?; basement membrane and lumenal epithelium (they are the basal cell lamina)

these epithelial cells are progenitors of other epithelial tissues; myoepithelial cells

basal lamina is a synonym for the...; basement membrane

what layers make up the basement membrane?; lamina densa and lamina rara (lucida) (NOT the lamina reticularis)

the lamina licida is also called the lamina...; rara

where is the lamina reticularis located?; next to but not part of the basement membrane

name three cell types that generally have a basement membrane; epithelium, nerves, muscles

basement membrane contains what type of collagen?; type 4

does type 4 collagen for fibers?; no, produces a felt-type of mesh

basement membrane is made of what two biomolecules?; type 4 collagen, glycoproteins

what type of glycoproteins are found in the basement membrane?; laminin, heparen sulfate proteoglycan

this laminar structure can help cells differentiate and knwo what type of cell to become; basement membrane

blistering diseases can arise from what pathology of the basement membrane?; poor anchoring of proteins

name four functions of the basememnt membrane; anchoring, signaling (differentiation), molecular filtering (think glomerulus), cellular filtering (think blood vessels)

name the three shapes of epithelium; squamous, columnar, cuboidal

name and describe the four types of layering of epitheilium; simple (one layer), stratified (multiple layers), transitional (umbrella cells and stretchable), pseudostratified (looks but isn't stratified)

what type of epithelium layering is found in the urinary passage and the bladder?; transitional epithelium

what are the two types of stratified squamous epithelium?; keratinized and unkeratinized

in epithelium, this is a location of weakness and lymphocyte accumulation; where two different types of epithelium meet

name the two types of glands and their subtypes; unicellular and multicellular (simple and complex)

this type of gland has no ducts; unicellular

do all multicellular glands have ducts?; the simplest don't have ducts but most multicellular glands have ducts

what differentiates a simple or complex multicellular gland?; whether the duct is branched or not

what type and subtype of gland are exocrine glands?; complex multicellular

what are the two types of secretory units of exocrine glands?; elongated (tubular) and rounded (acinar)

how do serous and mucus cells stain differently? why?; serous cells are basophillic and stain with eosin (deep pink) whereas mucus cells stain very faintly

what type of gland is the submandibular gland? what type of duct and secretory unit does it have? what type of secretion?; compound multicellular, complex (branched) ducts, tubularacinar (both tubular and rounded) secretory unit, mixed (both serous and mucus)

why does PAS (periodic acid-schiff stain) stain mucus cells deep magenta?; because mucus cells have lots of carbohydrates on their proteins

what method of secretion does the submandibular gland use?; merocrine (for both mucus and serous secretions)

PAS stains the basement membrane what color?; deep magenta, because of the glycoproteins

layers of vessels are called; tunics

name the three layers of the vessels; tunica intima (closest to lumen), tunica intermedia, tunica adventitia

second name for tunica adventitia; tunica externa

which vessel tunic contains muscle?; tunica intermedia

vessels surving vessels are called...; vasa vesorum

thickness of cell membrane (nm); 10 nm

capillaries have which tunics?; only the tunica intima

what cell type that accompanies capillaries can form new blood vessels?; pericytes

what makes continuous capillaries unique?; they have a relatively thick layer of cytoplasm

more leaky: fenestrated caps with or without diaphragm?; without

type of capillaries that proteins and cells can fit through?; sinusoidal

name the four types of capillaries; continuous, fenestrated, fenestrated with diaphragm

20110105 notes.txt

149.166.42.231 — Sat, 08 Jan 2011 16:46:15 GMT

Admin: moved 20110105 02 notes.txt to 20110105 02 nervous notes.txt

*started here on 01/05/2011 at 2PM.

===Lecture Objectives-Nervous System ===
#Describe the basic organization of the nervous system and the main structural features that distinguish the central nervous system from the peripheral nervous system.
#Define the unique cell types that make up nerve tissue and the structural specializations that distinguish neurons from glial and other supporting cell types.
#Understand the role of axonal transport in maintaining the structure and function of neuronal processes and synaptic terminals.
#Compare the structural and functional features of myelinated and unmyelinated axons and describe the basic events in axon myelination.
#Describe the structure and function of the synapse.
#Understand the structure of the spinal cord and the histological detail that distinguish the gray matter from the white matter.
#Compare and contrast the structure and organization of the somatic motor and visceral motor system.
#Define the structural features and functions of glial cell types.
#Understand structure/function correlates associated with nervous system pathologies including Alzheimer's disease, cerebral ischemia, multiple sclerosis and referred pain.

===NERVOUS SYSTEM ===
*Clinical relevance:
**11K injuries per year
**Stroke is third leading cuase of death and #1 cause of disability
**Parkinson's disease: 40K cases / year
***Neuronal degeneration
**Alzheimer's disease: 4.5 million cases, 100$ billion per year
***Brain volume decreases.

===Basic organization===
*Central nervous system (CNS)
**Brain:
***Gray matter and nuclei (surrounds the white area; there are also "nuclei" of grey mater in the center of the brain.
***white matter (nerve fiber tracts)
**Spinal cord:
*Peripheral nervous system:
**Ganglia: clusters of neuronal cell bodies.
**Nerve fibers:
***Efferent---motor, from CNS to peripheral
***Afferent: from peripheral to central, sensory
*Neurons and glial cells
**There are many more glial cells than neruons.

===Neurons===
*Neurons can be classified:
**Number of primary processes: multipolar (many processes), bipolar (two), pseudounipolar (rarely found in ...)
**Function: excitatory, inhibitory, modularatory
**By transmitter: gluatmic acid, GABAergic, dopamine, etc.
**Other: projection neurons, interneurons, pyramindianl neurons (shape), granule cells, etc.
*Examples
**multipolar, GABAergic, inhibitory, and has many spines (multi-spinous).
**?
**?
**Fake neuron, a large aspinous neuron, non-projection neuron (previous three are projection neurons)

===Cell body===
*AKA perikaryon, soma
*The nucleuous has a prominent nucleolus
Why?
*Have much rER, generates dots called Nissl bodies.
*Has golgi, MT (microtubules), and mts (mitochondria), IFs (called neurofilaments), lyposomes (lipofuscins).
*Mt look like cucumbers in shape.

===Dendrites===
*One of the two major types of processes: axons and dendrites.
*Dendrites receive inputs from all surrounding cells.
*There are primary dendrites that branch into small and smaller dendrites.
*There are samll dendrtitic spines
*There are apical and basalar dendrites.
*How do we determine apical versus basal?
**Apical will face away from the cortex of the brain (toward the exterior).
*There is a head and neck to the spines.
*What do the spines do?
**They seem to allow synapsing with neuron neighbors.

===Axon===
*Send info to ther neurons ("upward").
*Axons are much longer than dendrites.
*There is only one axon per nerve cell, though they can branch extensively.
*There is an axon hillock which is begun by the initial segment. Then there are collaterals given off and terminations in the "terminal".
*There are many MTs ant mts in the axon hilock.
*Axonal transprot moves material from the soma to the terminal and ''vice versa''.
**There are fast and slow transport of vesicles along the axon.
**Fast is several hundred mm / day
**Slow transport is a few mm / day, moves soluble components and cytoskeletal structures.
*There are two directions, too:
**Anterograde: from body to peripheral via '''kinesin'''
**Retrograde: from peripheral to body via '''dynein'''

===Synapse===
*The site of communication between two neurons.
*Two types of synapse:
**Electrical synapse
***Fxn through gap jxns
***Allows passage of ions form cell to cell.
***Few of these in mammals
***Very fast
**Chemical synapse
***Three components: presynaptic, synaptic cleft, postsynaptic.
***The postsynaptic component can be just about any part of the post-synaptic cell (dendrite, soma, axon, spine).
***Note that in chemical synapses, the signals must be converted from electrical in the presyn cell to chemical and back to electrical in the postsynap.
*How do synapses work?
**It's about the resting memebrane potential, the synaptic potential, and the action potential.
*Spines are not fixed; they are always changing in length, location, number of branches, etc.

===Glial cells===
*Oligodendrocytes in the CNS and Schwann cells in the PNS.
*Produce myeling sheath to cover axons.
*Myelin is a lipoportein complex, an insulation; keeps ions from flowing freely around the axon.
**With no myelin, bad transduction.
*In the CNS: a single oligodendrocyte generates the insulated area between nodes of ranvier.
*On an EM, the myelination shows as black area along the axon.
*Myelination and nodes of ranvier provide AP leaping which is faster.
*Unmyelinated firbers:
**In PNS, one schwann cell envelops many axons.
**No sheathes in CNS
**These have slow conductance.
Are all CNS / PNS myelinated / non myelinated?

===Spinal cord injury===
*Myelin is important for guiding regenerating axons.
*Bridging is an attempt to make regeneration work: put in a tube filled with schwann cells to help guide the regenerating axons passed the injury.
**It has been shown that axons may actually grow through the tube and help therapeutically.

===Astrocytes===
*Most numerous glial cells in CNS
*Two types
**Fibrous:
***Long, thin processes
**Protoplasmic astrocytes:
***Found in grey matter
***Short and fat processes
*Have end feet: connect to epithelium and sit on the external surface of the CNS
*Provide physical support for neurons
*Maintain homeostasis (toxin processing, extra NT processing, etc)
*Release neurotrophic factors (regulate transuction, still unknown)
*Can be found between two neurons and may help transduce signals
*Astrocytes can interact with neurons through the neuron's spine and their own form of a spine.
*Astrocytes are increased after ischemia of the brain (cns).
**So in early ischemia, astrocytes may proliferate in order to rescue the neurons.
**When ischemia is severe enough that neurons don't survive, the astrocytes generate a type of scarring material.

===Blood brain barrier===
*Important fxnal barrier to restrict exchange of substances between brain and blood.
*Has four components:
**Endothelial cells
***Provide an occluded junction which keeps even ions from passing between cells
***Have low transcytotic activity (that is, low transport into and out of the cytoplasm).
**There is a basement membrane
**There are end feet of astrocytes
**There are pericytes
***Provide another barrier in the BBB.
*All four of these form the BBB.

===Microglia===
*These are macrophages in the CNS
*Come from bone marrow
*In immune responses, they get turned on (IL4) and phagocytize stuff.
*They are generally very small compared to neurons and astrocytes.
*In MS, myelin is degenerated by microglia.
**In the inital phase: some pathogen enters the brain such that the microglia are activated.
**Then a second agent comes in and symptoms get worse.
**This gives the relapsing-remitting time-course of disease.
**There are abs generated against the myelin at increasing levels at each relapse.
*There are two forms of MS: RR and multi-organ MS.
**Many organs get attacked in MS.

===CNS===
*The brain is covered in neuro, we'll talk about spinal cord.
*There is a central canal which is lined with ependymal cells (celiated cuboidal epithelium).
*There is also grey matter
**Forms the dorsal, lateral, and ventral horns as well as the neuropil.
***Ventral = motor
***Dorsal = sensory
***Neuropil is anywhere without cell bodies.
*There is white matter:
**Descending and ascending fiber tracts

===PNS===
*Ganglia:
**Cell body collections
**Three types:
***Sensory,
***Autonomic ganglia
*Nerve fibers:
**myelinated and unmyelinated fibers
**Epineurium, perineurium, and endoneurium
***This is just like with muscle (endo / peri / epi myseum).
***A single neuron has myelin around it then the endoneurium.
***Several neurons will be bundled via perineurium.
***A whole nerve bundle will be surrounded by the epineurium.

===Somatic nerves===
*Two major types of nerves: somatic and visceral
*Two types of somatic nerves:
**Sensory
***Dorsal root ganglia
***Very precise as to where the signal came from.
**Motor
***from motor neurons to skeletal muscles
***Use ventral horn
***Fast
***Precise

===Visceral nerves===
*Control smooth muscle, glands, cardiac rhythm, and body homeostasis
*Two tyeps:
**Sensory
***From internal organs to CNS
***Go through DRG
***Difuse and vague
***Generate referred pain because conduction is back to the spinal cord, to the dorsal horn at the same place as the somatic sensory nerves. the brain may interpret the pain as somatic when it is actually visceral?
Can it be interpretted in the opposite way?
**Motor
***There is a sympathetic system
****The thoracolumbar division uses ach and sympathetic ganglia to control heart, glands, and smooth muscle
****Has short pregangliotic fibers and long post-gangliotic fibers.
****Functions to increase awareness and survival
***There is a parasympathetic system:
****the Craniosacral division uses ach and parasympathetic ganglia to control heart, gland, smooth muscle etc.
****The preganglionic fibers are relatively long; the postganglionic fibers are relatively short.
****Function to conserve energy.

==Lab==

===PERIPHERAL NERVE===

====Slide 9 sciatic nerve dog====
*Osmium tetroxide was used to fix these nerves.
**This preserves lipids and stains them brown or black.
**Adiposites in this slide show up as black.
**Myelin on this slide shows up as brown.
*The organization of the nerve fibers are seen:
**All three fibers are collagenous connective tissue.
**Epineurium is the outer layer:
***Coursest of the three layers
***Surrounds an entire '''nerve bundle'''
**Perineurium
***Surrounds the entire nerve bundle and projects deep into the bundle of axons to merge with the endoneurium.
***Easiest to identify it at the very outside edge of the axon.
***Seems a little more wavy and less collagenous than the epineurium.
**Endoneurium is the inner layer:
***Most delicate
***Immediately surrounds the myelinated axons.

*Myelin can be identified around each axon by it's brownish color that is circular in a cross-section and wide-spread in longitudinal cut.
**The myelin will surround the delicate endoneurium which is stained pink.
**Around the dark band of myelin, there is a small gap and then another, thinner dark band representing the outside edge of the schwann cells.
***This gap is larger than in real life as there is shrinkage of the myelin away from the schwann cell body.
*There is also shrinkage between the myelin and the cytoplasm of the axon which in this slide appears pink.

====Slide 15 Peripheral nerve====
*This slide is stained with Masson's trichrome
**Connective tissue will be a blue-green
**Nuclei will be a purple.
**Myelin is blotch white
*The schwann cell is wrapped around the axon so its nuclei stain is purple and arched around the axon like one expects the myelin to be.
*The nuclei of the distributed fibroblasts are slight better defined (sharper edges), are elongated, not arched, and are found in the midst of connective tissue (blue-green) as opposed to the blotchy whiteness of myelin.

*Unmyelinated axons can be seen on slide 15 and 9.
*These axons are tucked into invaginations of the cell membrane of schwann cells.
**These invaginations form channels for each axon.
**These will generally occur at very small axons.
**Recall that unmyelinated neurons will occur in the peripheral nervous system.
**These neurons will be to parasympathetic things like smooth muscle control because we don't need things to happen quickly.
*One cannot be sure that a neuron doesn't have myelin simply by light microscope so we are not responsible for determining if a neuron has myelin or not.

====Nodes of Ranvier====
*Nodes of Ranvier are generated by the end of one myelin covering and the beginning of another meet.
*The nodes can be identified in slide nine by the pinching of the pink endoneurium at a sharp point
**These nodes are very small in distance so with light microscope it is not possible to see the separation of the two myelin sheaths.
*Perpendicular to the pinched area will be a shriveled axon, much thinner than the distance between the layers of the endometrium on the sides of the axon.

====Slides 10, 82, and 25===
*"Other Examples of Peripheral Nerve: Several slides in the collection contain peripheral nerves. The nerves in slide 10 (mesentery) are easy to find. These are unmyelinated nerves. If you have time, take a look at slide 82 (spermatic cord) where most of the nerves are unmyelinated, and slide 25 (lymph node), which also contains unmyelinated fibers."
Need help finding neurons on slide 82.

===SPINAL CORD AND GANGLIA===
*Peripheral nerve fibers can contain somatic motor, visceral motor, and sensory neurons.
*The cell bodies of each neuron type is located in a specific area (either the spinal cord of the CNS or ganglia of the PNS):
*To understand why nervous tissues appear the way they do, it is helpful to understand where neuronal cell bodies reside.
*Be familiar with the following:
**Pseudounipolar (somatic or visceral) sensory neurons.
**Multipolar somatic motor neurons.
**Multipolar visceral preganglionic motor neurons.
**Multipolar visceral postganglionic motor neurons.

====Spinal Cord====

=====Slide 6 Spinal cord, cervical, monkey=====
*This slide uses a Nissl stain:
**Recall that rER in neurons is also called '''Nissl bodies'''
**Causes rER to be a deep blue
*In the ventral horn, multipolar visceral motor neurons can be identified by their heavy blue / purple staining of rER.
*

=====Slide 17 Spinal cord ganglion, mammal=====
*This is an H&E stain:
**Basophilic structures like the rER will be stained blue because of hematoxylin.
*One can identify the dorsal horn, the ventral horn, multipolar motor neurons in the ventral horn, and the dorsal root ganglion.
**Recall that the horns are grey matter, surrounded by white.
*The dorsal root sends afferent ("at" the CNS) fibers from the dorsal root ganglion to the dorsal horn of the spinal cord grey matter.
*The ventral root carries efferent ("exit" the CNS) fibers from the spinal cord to to visceral motor effectors.
*The ventral horn contains cell bodies of somatic motor neurons.
**These cells have much euchromatin and large nucleoli -- both signs of high metabolism.
*Multipolar cells will have several processes shooting off.
**There is however, only one axon.
**The axon may not be the largest process.
**The axon can be identified by the presence of the axon hillock.
**The axon hillock will stain lighter than rest of the cell because it has many MTs but little rER and few mt.

*"Neurons dispersed within tissue that has almost no intercellular space. Nuclei of the surrounding cells are easily visible, but cell boundaries are hard to see. There are many capillaries present, but most of the nuclei in the surrounding tissue belong to glial cells. The material surrounding the cell bodies is composed of processes of neurons and other glial cells, and is called the neuropil (a feature of the CNS)."

*The white matter has much smaller nuclei and a more homogenous speckled look (probably because the cells are running into and out of the cross-section instead of branching in parallel with the cross-section cut).
*Is there a name for the cells that bridge the grey and white matter?

*stopped here on 01/05/11 at 6PM.
*started here on 01/07/11 at 12:45PM.

*The lateral horn houses cell bodies of autonomic motor neurons that innervate smooth muscle and glands.
*Somatic motor neuron axons run through the ventral root and bypass the DRG.
*Visceral motor neurons have cell bodies in the ventral horn; axons travel through the ventral root, bypass the dorsal root ganglion, follow nerves that lead to peripheral ganglia.
But they don't synapse in the peripheral ganglia?
They just synapse directly on the motor cells?
**Note that this is a one-cell communication between the CNS (spinal cord) and the effector cell (skeletal muscle).
*The autonomic nervous system takes two cells for CNS-to-effector communication.
**Here there are preganglionic cells and post ganglionic cells with ganglia as their point of synapse.
**The cell body of the preganglionic cells is in the spinal cord.
**The cell body of the postganglionic cells is in the respective ganglia.
*There are two divisions to the autonomic nervous system: parasympathetic and sympathetic.
**The sympathetic system is characterized by short pre-ganglionic axons that synapse in ganglia that is very near to the spinal cord (think "sympathetic chain ganglion", etc.).
***Subsequently, the post-ganglionic fibers are much longer as they run to their effector cells.
**The parasympathetic system is characterized by long pre-ganglionic fibers that run to ganglia that are far from the spinal cord.
***Subsequently, the post-ganglionic fibers of parasympathetics are short fibers that run to effector cells that are close to their ganglia.

=====Structures=====
*Be able to find:
**White matter
**Grey matter
**Dorsal, ventra, and lateral horn
**Ventral root
**Dorsal root
**DRG
**Multipolar motor neurons (ventral horn)
**Axon hillock
**Nissl bodies
**Neuroglia
**Neurophil

====Dorsal Root Ganglion====

=====Slide 17=====
*In slide 17 one can see a dorsal root ganglion attached to the spinal cord.
*The dorsal root ganglion holds cell bodies of sensory neurons.
*These sensory neurons give off only one process, but it quickly splits into two.
**This is called '''pseudounipolar'''.
**One process heads to the spinal cord via the dorsal root, then horn.
***This process will synapse in the spinal cord with a neuron that will transduce the signal up the spinal cord.
**One process heads to the effector sensory cell.
*These sensory cells can be carrying either somatic or visceral sensory input.
*Sensory cells of the dorsal root ganglia are highly active and therefore have large nuclei, lots of euchromatin, and prominent nucleoli.
**Furthermore, they have lots of supporting cells surrounding them: '''satellite cells'''.
Look also for myelinated nerve fibers within the ganglion.

*Be able to identify:
**Dorsal Root Ganglion
***pseudounipolar somatic and visceral afferent ("at" the CNS) fibers.
**Ventral horn
***Multipolar somatic efferent ("exit" the CNS) fibers.
**Lateral horn
***Multipolar visceral efferent ("exit" the CNS) preganglionic fibers
***Multipolar visceral efferent ("exit" the CNS) postganglionic fibers
**Vertebral ganglion.
**Prevertebral ganglion.

====Autonomic Ganglion====

=====Slide 12=====
*This slide is of the sympathetic ganglia, which is part of the autonomic nervous system.
*Nissl stain and lipofuscin were used:
**Nissl causes rER to stain pink
**Lipofuscin gives cells a brown color
*Recall that ganglia are where post-synaptic cell bodies reside and synapse between pre-syn and post-syn neurons occurs.
**More specifically, because this is a sympathetic ganglia, short pre-synaptic fibers are synapsing upon bodies of long post-synaptic cells.
**And because this is a sympathetic ganglion, these neurons are visceral motor neurons.
***These will be efferent ("exit" the CNS) fibers.
*Sympathetic, visceral, post-synaptic motor neurons are:
**Multipolar
***But it is harder to see their processes than with the somatic motor neuron bodies of the ventral horn (which are also multipolar).
*Neurons in the sympathetic ganglion are surrounded by satellite cells.
**However, these satellite cells are not as numerous or tightly packed as those that we saw surrounding the neurons in the DRG (slide 17).
*One should also be able to identify myelinated and unmyelinated axons passing through the sympathetic ganglion.

====Miscellaneous====
*Osmium tetroxide preverves lipids (like those of myelin).
**Makes adiposites dark black because of all the lipids they hold.
**Makes myelin brownish around the axon of neuron.
*The three-neuriums are all connective tissue.
**Endoneurium is the most delicate.
**Epineurium is coarse connective tissue.
**Perineurium surrounds the nerve and projects deep into the bundle of axons where it blends with the endoneurium.

*stopped here on 01/07/11 at 2:15PM

20110103 notes.txt

149.166.42.231 — Sat, 08 Jan 2011 16:45:44 GMT

Admin: moved 20110103 01 notes.txt to 20110103 01 muscle notes.txt

*started here on 01/03/2011 at 2PM

===What is this course===
*Structure-function correlation
*Structural foundation for physiology and pathology.
*Mescher writes the text book; he's at the Bloomington campus.

===Communication===
*Lecture slides posted on ANGEL
*Only 21 or 22 lectures.
*Three unit exams.
**Very thorough assessment.
**Exams are not cummulative.
*Last exam is NBME.
**Usually pretty reasonable.

===Lab===
*109-116
*Good place for studying
*Leo Thompson (MS 108)
**Fixes microscopes
*Alphabet starts in 114-116: A-O'Banner, then 109-110.
*Find your name in the lab, find your drawer, find your paper, key, and slides.
**Key on drawer goes on key ring; the other one stays in the drawer and opens the microscope cabinet.
*Ability to learn is a function of how well you use your microscope, so let them help you learn.

==Lecture==

===Classes of Tissue in Histo===
*Muscle (for contraction), nearve (for conduction), epithelium (for barriers, for glands), connective tissue (for holding things together and up).

===Slide ===
*

===Muscle===
*Skeletal muscle
*cardiac muscle
*Smooth muscle

===Skeletal muscle===
*Long
*A form of striated muscle (like cardiac)
*Have more than one nucleus
**Located at periphery
*Each muscle cell = a muscle fiber; interchangable.
*Myofibril (not a fiber) is an individual contractile intracellular organelle.
*Myofibrils are surrounded by the sarcoplasmic reticulum.
**Sarco from greek Sarcs = flesh.
*Cytoplasm = sarcoplasm.
*Sarcolemma = cell membrane

===Image===
*Striations are clear in longitudinal cut of striated muscle.
*Nucleus is at the periphery.
*Myofibrils can separate a bit within a cell.
*Human RBC = 7 micrometers across.
*Sections are 5-7 microns thick and are cut with a knife.
**This means there are some artifacts.

===Myofibrils===
*They are surrounded by sarcoplasmic reticulum.
*Skeletal muscle cells have a basement membrane on the outside of the sarcolemma, too.

===Muscle cuts===
*Fasicles are bundles of many muscle cells.
*Within a whole muscle lies individual cells which are held together by '''endomyseum'''.
*Bundles are defined by perimyseium.
*The epimyseum lies around an entire muscle.

===Myofiber in detail===
*Myofibrils are visible.
*The sarcomere is the contractile unit that is repeated to generate myofibrils.
*Thick and thin filaments make up the sarcomere and generate the striations.
*There is area where there is no thick filaments: called I bands because they don't change the orientation of polarized light.
*A bands are where thick filaments exist; they do change orientation of light.
*Z lines are where the thing filaments are anchored.
*The M line (may or may not be visible in EM) is where thick filaments are anchored.
*The H zone is where thick filaments don't overlap; surrounds M line.
*We should be able to identify all of these on an EM (electron micrograph).

===EM of Muscle===

===Myofilaments in detail===
*Thin filaments made of globular actin (which polymerizes to form filamentous actin).
*Thin filaments also have troponin complex and tropomyosin.
*Thick filaments are made of myosin.
*Thick filaments have a sort of long tail with two heads that come off like pineapple fruit.
*Myosin walks along the thin filament, pulling the thick filaments along the thin.

===Contraction in detail===
*Myosin has an ATPase site in each head which burns ATP down to ADP and Pi.
**The units are not released immediately after burn, though.
*If Ca+ is low, then tropomyosin will inhibit myosin to bind to thin filament.
**So ADP and Pi will be held on myosin but bind and contraction are not occurring.
*If Ca+ rises to 1 micromolar or greater, then Ca binds to TnC (troponin subunit of thin filament).
*TnI and TnT (parts of troponin) then are involved in conformational change.
**TnI binds actin.
**TnT binds tropomyosin.
*Calcium binding on troponin changes the conformation of troponin such that TnI comes up off actin which allows tropomyosin to move about 5 minutes around the clock face of the actin.
*This allows the head of myosin to bind in on the thing filament.
*Upon binding to actin, the Pi is released from myosin. This causes a conformational change--the '''power stroke'''.
*After the conformational change, the ADP is released.
*Release of ADP and Pi makes myosin high affinity for ATP such that it binds and gets burned causing a release of myosin from actin (hence ''rigor mortis'').

===Sarcoplasmic reticulum and calcium transport===
*Rise in Ca+ causes contraction.
*But these cells are huge, so how do we cause such an increase in an ion?
**In a normal cell we could just open the calcium channels and let it flow in, but it muscles it would take a long time for calcium to diffuse throughout.
**So we have a sarcoplasmic reticulum to deliver the Ca+ throughout the cell.
*The nerve signal comes from the outside the cell and depolarizes the membrane. But how does it talk to the sarcoplasmic reticulum?
**Via transverse tubules (T tubules)
**These stretch from cell membrane into the cell to touch the Sarcoplasmic reticulum via terminal cisternae.
**Two terminal cisternae with a A-I junction in between is called the triad.
*T tubules have a bit of basememnt membrane that dives into the cell along with the T cell.
*Note that mammals have T tuble going to A-I jxn whereas in others it goes to the Z line.

===Getting signal to muscle cell===
*Motor neuron brings the signal.
*Neuron and muscle jxn = synapse = nerve plate.
*One axon may innervate one myofiber or dozens.
*A motor unit is a single neuron and all the muscles it innervates.
**Motor units are either all or none; all cells contract when signaled.
**In the eye, we get fine motion and control becuase we have one nerve axon per myofiber.
**In the back, we have many myofibers per neuron because we don't need fine movement.

===Cardiac Muscle===
*Striated like skeletal muscle with some unique structures.
*Cardiac has branched cells; ;which are joined physically and electrically.
**Skeletal cells may be connected physically but not electrically.
**Skeletal don't pick up signal to fire from neighbors, but cardiac cells do, via electrical connection.
*Cardiac muslce have centrally located nuclei and only 1 or 2 nuclei.
*Something different about sarcolemma, too.
*Cardiac structures have intercalated disks which connect them to one another.
*Cardiac muscle is highly vascular but skeletal is much more limited.

===Intercalated disks===
*Allo cardiac cells to bind end to end.
*Have three junctions:
**Facial adherens
***Where thin filaments are joined together.
***A bit like zonula adherens.
***Where thin filaments joined to function as one between cells.
**Macula adherens
***Just a desmosome
***Where thick filaments pass between cells (?).
**Gap juctions
***Electrical connections.
***membranes come together very close at gap jucntions
***Don't physically hold cells together because they don't affect cytoskeleton.
***Occur along the longitudinal axis of the muscle cells, generally.
*Diads occur in cardiac cells...don't see one of the things of the triad; don't know what it was.
*ANP atrial naturetic peptid is released by what?

===Smooth muscle===
*All the cells are spindle shaped--a rod with tapered ends.
*Central nuclei.
*Much smaller than cardiac cells.
*In a cross section the cells are cut at different levels because of their tapering.
What is a "typical HNE cut"?
*Smooth muscles have thick and thin filaments but they are not organized into sarcomeres.
**They are also attached to intermediate filaments made of desmin and vimentin.
*Thin and intermediate filaments are linked by cytoplasmic '''dense bodies''' and membrane by '''membrane dense bodies'''.
**These cause dark bodies on the membrane and out in the cytoplasma.
**Dense bodies are where contractile skeleton connects to cytoskeleton.

===Contraction===
*Regulated in part by assembly and disassembly of intermediate filaments.
*Don't need T tubles to stimulate contraction because they are small.
*Stimulation causes phos of myosin which causes them to assemble inot thick filaments, allowing contraction.
*There is more regulation but we won't talk about it.
*Contraction is stopped by activation of phosphatase which cleaves off phosphorous of myosin and depolymerization.
*Smooth muscle contraction scrunches the cell into shorter and fatter, ball-like shape.
**This can cause the nucleus to corkscrew.

===Junctions in Smooth muscles===
*Can have gap jxns which means neighbors act in coordinate fasion: '''unitary smooth muscle'''
*Multi-unit smooth muscle is more tightly controlled by individual neruons.

===Regeneration of skeletal muscle===
*Because of satellite cells, we can regnerate some skeletal cells.
*Most smooth muscle can dedifferentiate and generate new cells.
*Cardiac cells cannot regenerate, only form fibrotic tissue.
*Process of skeletal regen:
**Satellite cells -> myoblasts -> myotubles (long, multiple cells bound together) -> myofibrillogenesis (fusion of cells) -> myofiber
**Satellite cells
***Reside just below basement membrane next to skeletal cells.
***May look like peripheral nucleus or fibroblast in our slides.
**Myoblasts
***Don't look like muscle cells but have similar expressiokn patterns.
***Can fuse to other myoblasts.
**Myotubes
***A syncitium of myoblasts.
**Myofibrillogenesis
***Formation of myofibrils of myotubes.
***Pushes nuclei outward
***Elongates cell.
**Myofiber

==Lab==

===Staining===
*H&E = hematoxylin and eosin
**Hematoxylin stains blue
***Hemotoxylin binds to acidic particles because it is basic.
***Stains upon reaction with Fe and Al.
***Stains chromatin, ribosomes,
**Eosin stains red / orange.
***Stains acidic particles.
***Stains connective tissue, cytoplasm, collagen, muscle fibers, and mt.

===Miscellaneous===
*Fats are dissolved away in fixation process leaving some areas vacant of tissue.
*Because these specimens were "immersion fixed" there may be RBCs floating around.
**RBCs are around 7 micrometers in diameter but around 10 micrometers when found in their normal environment--the vessel.
*Is the dark spot within the nucleus the nucleolus or the heterochromatin?
**It is the nucleolus.
**The difference between heterochromatin and euchromatin is a darkness thing; heterochromatin will be darker because it is condensed. The size of the nucleus will not necessarily change with the difference in hetero and euchromatin.
*Liver cells are typically 20-30 micrometers.
**So a 6-8 micrometer slice will not capture it all.
*Don't rely on color for identification.
*Nuclei of all types of muscle may corkscrew upon fixation.

===Smooth muscle===
*Uterus, appendix, bladder.
*The appendix (and the rest of the GI tract) has an inner circumferential and outer longitudinal layer of smooth muscle.
**The stomach is the opposite, though.
*The uterus has interlaced bundles of smooth muscle.
*The bladder has disparate bundles separated by connective tissue.
*Connective tissue is often stained an intense red (from eosin) and has few (fibroblast) nuclei present.

===Skeletal muscle===
*Soft palate, tongue,
*The soft palate showed glandular tissue, too, I think.
*There are transverse striations visible in skeletal muscle.
*Nuclei are many and on the periphery.
Is there connective tissue at the angular connections of differently oriented striations?
*Myofibrils appear as longitudinal striations in a longitudinal cut and as stippling in a cross-sectional cut.
*Myofibers are surrounded by endomysium; muscle cell bundles are surrounded by perimysium; gross muscles are surrounded by epimysium.

===Cardiac muscle===
*Striated
*Heart
*One or two nuclei per cell, centrally located.
*Cardiac muscle has intercalated disks and branched muscle cells.

*stopped here on 01/03/2011 at 5:35PM

Main Page

Admin — Mon, 14 Dec 2009 16:07:03 GMT

24.15.60.132:

*[[P's NBME study guide]]

===Exam 3===
*[[Eye]] (04/11/2011, McAteer)
*[[Skin]] (04/06/2011, Plotkin)
*[[Male reproductive]] (04/04/2011, McAteer)
*[[Female reproductive]] (03/28-30/2011, Williams)
*[[Endocrine]] (03/24/2011, )
*[[Urinary 1 and 2]] (03/21-23/2011, Williams)

*[[P's exam 3 study guide]]

===Exam 2===
*[[Practice exam for exam 2]]
*[[Bone and cartilage]] (02/21-23/2011, Allen)
*[[GI - Glands]] (02/16/2011, Williams)
*[[GI - Small intestine through anus]] (02/14/2011, Williams)
*[[GI - Mouth through stomach]] (02/09/2011, Williams)

===Exam 1===
*[[exam_1_flashcards.txt]] (tdf)
*[[20110131_10_respiratory_notes]]
*[[20110126_07_lymphoid_organs_notes]]
*[[20110124_06_connective_cells_notes]]
*[[20110119_05_connective_tissue_notes]]
*[[20110112_04_circulatory_notes.txt]]
*[[20110110_03_epithelium_notes.txt]]
*[[20110105_02_nervous_notes.txt]]
*[[20110103_01_muscle_notes.txt]]