P's NBME study guide

From Iusmhistology

Revision as of 01:00, 18 April 2011 (edit) 24.15.60.132 (Talk) ← Older edit		Revision as of 01:47, 18 April 2011 (edit) (undo) 24.15.60.132 (Talk) Newer edit →
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	==GI==		==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====		====Hard palate====
	*Parakeratinized = for dealing with rough surfaces		*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====		====Tongue====
-	*Bumps are called papillae.
	*Filiform papillae provide roughness.		*Filiform papillae provide roughness.
-	**Cats have very sharp, extended filiform papillae.
	*Filiform are rod like and have a parakeratinized surface.		*Filiform are rod like and have a parakeratinized surface.
	*Fungiform papillae have bulbous ends.		*Fungiform papillae have bulbous ends.
	**These are the red bumps on our tongues.		**These are the red bumps on our tongues.
-	**Fungiform DO NOT have parakeratinized.
	*Circumvallate papillae		*Circumvallate papillae
-	**In the back.
-	**Have a valley.
	**Valleys are flushed by serous glands called glands of Von Ebner.		**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		*Geographic tongue
-	**2% of people have this
-	**Comes with eating certain foods.
	**A kind of psoriasis of the tongue.		**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====
	*Gingiva = gums of the mouth.		*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.		**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.		*Enamel covers the crown.
	**Mostly appetite		**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=====		=====Periodontal ligament=====
	*Run between cementum and the alveolar bone.		*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).	+	bundles of collagen
-	*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.		*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.		*Scurvvy: teeth fall out because ligament doesn't get regnerated becuase new collagen can't be generated.
	===Gut tube===		===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===		===Esophagus===
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	**Has no glands (for the most part)		**Has no glands (for the most part)
	**Muscularis mucosae: has longitudinal muscle, not continuous		**Muscularis mucosae: has longitudinal muscle, not continuous
-	**Know these three properties!
	*The submucosa '''does''' have glands		*The submucosa '''does''' have glands
-	**Provide lubrication for the esophagus.
	*Muscularis externus		*Muscularis externus
	**Have inner circular and outer longitudinal muscle layers		**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		*Serosa
	**Mostly just CT (adventitia)		**Mostly just CT (adventitia)
Line 589:		Line 480:
	*Txn from esoph to stomach: squamous non-kera epith to simple columnar epithelium.		*Txn from esoph to stomach: squamous non-kera epith to simple columnar epithelium.
	*Also, we start to see tubular glands.		*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.		*Lned with surface mucus cells.
	*Surface invaginates into pits where glands empty.		*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.
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	**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.		**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.		**Parietal cells of the fundus / body make acids.
-	***Sometimes have two nuclei.
	**The neck region has parietal and undiffed cells.		**The neck region has parietal and undiffed cells.
	**Base has parietal and chief cells.		**Base has parietal and chief cells.
-	***Recall that chief are much darker staining (basophilic).
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	===A. ORAL CAVITY.===		===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.
-
-
-
-	*started here on 02/14/11 at 2PM.
	==GI - Small intestine through anus==		==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===		===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:		*Stem cells:
-	**Reproduce all other types
	**Live in the neck of the gland		**Live in the neck of the gland
	*Mucus neck cells:		*Mucus neck cells:
	**Usuaqlly in neck		**Usuaqlly in neck
	**Can't be distinguished versus stem cells		**Can't be distinguished versus stem cells
-	**Produce mucus	+
		+
	*Parietal cells = oxynctic cells		*Parietal cells = oxynctic cells
	**In the neck		**In the neck
Line 751:		Line 523:
	====Stomach images====		====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:		*Parietal cells:
-	**Tend to bulge out from the walls of the gland
	**Look like fried eggs.		**Look like fried eggs.
		+
		+
	*Acid secretion:		*Acid secretion:
	**Occurs by fusion of tubulovesicles with a secretory canaliculus.		**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.		**Bicarb moves in the opposite direction of acid.
	====Chief cells====		====Chief cells====
	*Produce, store, and then secrete pepsinogen (a zymogen).		*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.		*Pairetal cells live in both the neck and the base of the gland.
		+
	=====Enteroendocrine cells=====		=====Enteroendocrine cells=====
	*ADUP-type (amine precursur uptake and decarobxylation): the name for production of hormone produced by these cells.		*ADUP-type (amine precursur uptake and decarobxylation): the name for production of hormone produced by these cells.
	*Scattered through epithelium		*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====		====Pylorus====
Line 799:		Line 553:
	===Small intestine===		===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.		*Absorptive cells are called enterocytes.
-	*Lots and lots of surface area!
	*The muscularis mucosa and lamina propria are folded within the plicae circulares.		*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.	+	*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 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====		====Glands of the si====
	*These are simple tubular glands		*These are simple tubular glands
	*Called crypts of lieberkuhn.		*Called crypts of lieberkuhn.
-	*In both si and li but different.	+
		+
	*SI:		*SI:
	**crypts are the locaiton of stem cells		**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		**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.		***may be important for crohn's disease.
-	*Submucoals glands found only in the duodenum	+
		+
		+	*LI:
	**Called Brunner's glands		**Called Brunner's glands
-	**Mostly mucus glands	+
-	**Mostly alkaline secretion (to counteract the acid secretion)	+
	*Muscularis externa:		*Muscularis externa:
	**Inner cicrular, outer longitudinal.		**Inner cicrular, outer longitudinal.
-	*Serosa of the SI:	+
-	**Retroperitoneal parts don't have mesophthelium but most does	+
	*Nerve plexuses:		*Nerve plexuses:
-	**Myenteric plexus = auerbach's: between the two layers 9of the musculara externa (inner cirular, outer longitudinal)	+	**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	+	**Meissner's plexus = submucosa: runs within the submucosa = extrinsic innervation
	**Both are found in the large and small intestine.		**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===		===Large intesstine===
-	*Cecum  and colon are very similar.
-	*In the LI there are many long cryps of lieberkuhn and no submucosal glands
	*Mucosa:		*Mucosa:
	**There are simple columnar absorptive epithelial cells		**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:		*Muscularis externa:
	**Has outer longitudinal muscle with special bands called tenia coli.		**Has outer longitudinal muscle with special bands called tenia coli.
Line 887:		Line 589:
	**This is a thickening of outer longitudinal muscle bands.		**This is a thickening of outer longitudinal muscle bands.
	**the poutches help hold the food material as it is turned into feces.		**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===		===Cell turnover===
	*3-6 days in SI		*3-6 days in SI
	*4-8 days in LI		*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==
-
-
-
-	*started here on 02/16/11 at 2PM.
-	*Be careful veryifying one's knowledge with online resources because they can be wrong.
-	*
	==Glands==		==Glands==
-	*We'll do salivary, pancreas, and liver
	===Salivary glands===		===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		*Demilunes
	**Here serous cells are found		**Here serous cells are found
		+
		+
	*Two types of ducts:		*Two types of ducts:
	**Intercalated		**Intercalated
	**Striated		**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====	+	*Also there are interlobular ducts in the connective tissue.
-	*Have lots of serous acini	+	**Also called excretory
-	**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===		===Salivary===
Line 962:		Line 618:
	*Low in Na because it helps the taste bud fxn.		*Low in Na because it helps the taste bud fxn.
	*Alkaline, has bicarb to buffer acid		*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:		*Protein components:
-	**alpha-amylase: starts breaking down carbs
	**Proline rich protiens		**Proline rich protiens
	***Abundant		***Abundant
	***Antibacterial		***Antibacterial
	***Help coat the tooth and keep bacteria off		***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====		====Secretion====
Line 995:		Line 637:
	====Endocrine====		====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		*Beta = insulin
	*Alpha = glucagon		*Alpha = glucagon
-	*Alaph and beta make up most of the mass
	*Delta = somatostatin		*Delta = somatostatin
-	*alpha (20%), beta (70), d (5-10), F (1)
	*F cells generate pancreatic polypeptide.		*F cells generate pancreatic polypeptide.
Line 1,008:		Line 646:
	**But has not fatty tissue		**But has not fatty tissue
	**Has no striated ducts		**Has no striated ducts
		+
		+
	*Cholesystokinin = the hormone that moves the gallbladder		*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:		*Proteases are the main product of serous cells in the pancreas:
	**Trypsin		**Trypsin
Line 1,019:		Line 659:
	**Lipases		**Lipases
	**nucleases		**nucleases
-	*Volume of fluid (water and salt) is secreted by ductal cells	+
		+
	*Secretin stimulates ductal cells to generate the volume (water and salt)		*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:		*Acinar cells:
	**Well staining cyto and open nuc		**Well staining cyto and open nuc
Line 1,033:		Line 669:
	===Liver===		===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.		*70-80% of the blood comes from the hapatic portal vein.
	*The rest is oxygenated and comes from the hapatic artery.		*The rest is oxygenated and comes from the hapatic artery.
	====Hepatic blood flow====		====Hepatic blood flow====
-	*Blood flows between cords (a string of cells) or plates of hepatocytes.
	*Blood spaces are sinusoids, a form of sinusoidal capillary		*Blood spaces are sinusoids, a form of sinusoidal capillary
	**Incompletely lined with endothelium; the endothelial cells don't bind to one another		**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====		====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:		*Three ways to understand how hepatocytes filter blood and produce and bile:
	**Liver can be lobulated:		**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		***The liver is divided into lobules that have protal veins, hepatic arteries and ducts at one side and
	**Portal lobule		**Portal lobule
Line 1,097:		Line 684:
	**Hepatic acinus		**Hepatic acinus
	***Lobule defined by hepatocytes' blood source		***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===		===Gallbladder===
-	*The point is to store and concentrate the bile until fatty foods are present.
	*Epithlium of gall bladder are simnple columnar epithelium		*Epithlium of gall bladder are simnple columnar epithelium
	**Has brush border		**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:		*Muscularis:
-	**Sometimes a pouch of epithelium pokes thorugh and LOOKs like a gland but isn't.
	*True serosis is present		*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.
-
-
-
-	*started here on 02/21/11 at 1PM.
	==Bone and Cartilage==		==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===		===Bone cells===
	====Osteoclasts====		====Osteoclasts====
-	*Large	+	*Rank ligand essential for diff into preosteoclast and full osteoclast.
-	*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 osteoblasts
-	**Made by other cells of the bone marrow.	+
-	**Attaches to rank receptor on pre-osteocblasts	+
-	*Multiple osteoclasts fuse to form multinucleate	+
	*OPG		*OPG
	**A decoy receptors for rank ligand		**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	+	*Generates a "focal zone"
-	**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:		*Enzymes for resorption:
-	**TRAP	+	**TRAP = Tartrate-resistant alkaline phosphatase
-	***Tartrate-resistant alkaline phosphatase	+
	***Can be assessed in blood to know how much activity of osteoclasts is occurring		***Can be assessed in blood to know how much activity of osteoclasts is occurring
	**Cathepsin K		**Cathepsin K
		+
		+
	*Houshets lacuna		*Houshets lacuna
	**Well in bone where resorption has occurred.		**Well in bone where resorption has occurred.
	===Osteoblast===		===Osteoblast===
-	*Located on bone surface
-	*Secrete osteoid
-	**Osteoid is unmineralized
-	*Osteoid ges minieralized eventually.
	*Come from mesenchymal cells		*Come from mesenchymal cells
	**Need runks2 and ostrix		**Need runks2 and ostrix
-	**Without you get no bone	+
-	*Runks2	+
-	*Ostrix	+
	*Alkaline phosphatase is key protein involved in matrix production		*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===		===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		*Connected to each other and to the bone surface by filopodial processes
	**These live in channels called canaliculi		**These live in channels called canaliculi
	**Connected via gap junctions.		**Connected via gap junctions.
		+
		+
	*There is one osteocyte per lacunae.		*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====		====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.		*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===		===Bone matrix===
	*Made of type 1 collagen.		*Made of type 1 collagen.
	**A fibrous 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.	+	*C-propeptide in the blood means there is bone formation
-	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.	+
Line 1,288:		Line 746:
	**Know osteopontin, osteonectin, and ostecalcin		**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.		**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===		===Tyeps of bone tissue===
Line 1,308:		Line 761:
	====Lamellar bone====		====Lamellar bone====
	*AKA secondary bone, mature 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.		*Higher mecanical strength than primary.
	*Lamellae:		*Lamellae:
Line 1,320:		Line 769:
	===Bone anatomy===		===Bone anatomy===
-	*Cortical or cancellous bone	+	*Cortical is called compact
-	**Cortical is called compact	+	**This is the outer part
-	***This is the outer part	+	**Main fxn is structural
-	***Main fxn is structural	+	**PRovide resistance to loading
-	***PRovide resistance to loading	+
-	**Cancellous bone = spongy bone = trabecular	+
-	***NOT squishy	+	*Cancellous bone = spongy bone = trabecular
-	***Small piece of cancellous and small piece of cortical would looke the same.	+	**NOT squishy
-	*Four different surfaces:	+	**Small piece of cancellous and small piece of cortical would looke the same.
-	**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====		====Haversion systems====
	*AKA osteons		*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		*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====		====Periosteum====
Line 1,356:		Line 793:
	===Structures===		===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.	+	==Cartilage==
	===Hyline cartilage===		===Hyline cartilage===
-	*Found in joints, respiratory passages, ends of ribs, within bones
	*Made of type 2 collagen fibrils		*Made of type 2 collagen fibrils
-	*Has some non-collageneous proteins proteoglycan aggregates.	+
		+
	*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.
Line 1,385:		Line 809:
	*Condrocytes:		*Condrocytes:
-	**Retain mitotic activity
-	***Unlike osteoclasts
-	**Can form 2, 4 or even more cells within its region.
	**These units are called isogenous groups.		**These units are called isogenous groups.
	*Hyline matrix:		*Hyline matrix:
-	**It is not uniform.
	**Terirtorial matrix = capsular		**Terirtorial matrix = capsular
	***Found just around a chondrocyte		***Found just around a chondrocyte
-	***Capsule is found closer
	**INterteritorial matrix		**INterteritorial matrix
	***Found farther out.		***Found farther out.
	**The collagen fibrils are smaller in the territorial matrix		**The collagen fibrils are smaller in the territorial matrix
-	**The types of pg are different in the territorial than interterritorial.
Line 1,411:		Line 829:
	*Has type 1 collagen in it.		*Has type 1 collagen in it.
	**Forms fibers called rows or chords		**Forms fibers called rows or chords
-	*Between chords are the chondrocytes
	*Has no perichondrium		*Has no perichondrium
-	*Can serve as a transition between tissues like tendon and bone.
-
	===Elastic cartilage===		===Elastic cartilage===
	*Found in the ear, epiglottis, and the larynx		*Found in the ear, epiglottis, and the larynx
	*Has type 2 collagen		*Has type 2 collagen
-	**Fibrils
	*Elastic fibers also present		*Elastic fibers also present
	*Has a pericondrium		*Has a pericondrium
Line 1,425:		Line 839:
-	*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==		==Joints==
Line 1,458:		Line 844:
	===Synarthroses===		===Synarthroses===
	*Very little movement		*Very little movement
-	*Can be bone to bone or bone to hyline to bone or bone to fibrous to bone.
	===Diarthrovidal (synovial) joints===		===Diarthrovidal (synovial) joints===
	*Have a cavity with fluid		*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====		====Articular cartilage====
	*This is hyline cartilage		*This is hyline cartilage
	*Articular cartilage has type 2 collagen with '''fibrils''' not ''fibers''.		*Articular cartilage has type 2 collagen with '''fibrils''' not ''fibers''.
		+
		+
	*There are several zones:		*There are several zones:
	**Superficial zone: in intimate contact with the cavity; has very few condrocytes; mostly type 2 collage fibrils; resists sheer forces		**Superficial zone: in intimate contact with the cavity; has very few condrocytes; mostly type 2 collage fibrils; resists sheer forces
Line 1,476:		Line 862:
	tidemark		tidemark
-	How do you tell the diff between calcified and non calcified cartilage?
	====Joint capsule====		====Joint capsule====
	*Capsule is continuous with the periosteum		*Capsule is continuous with the periosteum
	*Periostium has two layers: fibrous and cellular layer		*Periostium has two layers: fibrous and cellular layer
-	*As it starts to cover the capsule, though, it loses it's 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		*Surface of the synovial membrane is not covered with epithelial cells
	**A rare occurance in the body.		**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 Synoviocyte:
-	*Type A:	+
	**Found on surface of the synovial membrane		**Found on surface of the synovial membrane
	**Look like epithelium but are not because they are not connected together.		**Look like epithelium but are not because they are not connected together.
	**Act like macrophages to detect and phag foreign particles.		**Act like macrophages to detect and phag foreign particles.
	**Uusually 1 cell deep but can be 2 to 3 deep.		**Uusually 1 cell deep but can be 2 to 3 deep.
-	*Type B:	+
-	**Deeper within the matrix	+	*Type B Synoviocyte:
	**A fibroblast like cell		**A fibroblast like cell
	**Makes hyaluronic acid		**Makes hyaluronic acid
Line 1,505:		Line 888:
	====Osteoarthritis and Rheumatoid arthritis====		====Osteoarthritis and Rheumatoid arthritis====
-	*AKA OA and RA
	*OA:		*OA:
	**Mechanical		**Mechanical
Line 1,514:		Line 896:
	==Chondrogenesis==		==Chondrogenesis==
-	*Chondrocytes produce matrix	+	*When matrix made "within" existing cartilage, the cells will separate from one another; this is how the bone is lengthened at the epiphyseal plates.
-	*Then chondrocytes divide	+	*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.
-	*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==		==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.		*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.		*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.		*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==		==Endochondrial bone formation==
	*Here we start with a template on and in which we build bone.		*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	+	*There are 5 zones.
-	**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 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		**Zone of proliferation: chondrocytes become align and form rows and columns of chondrocytes (stacked coins) which contributes to bone growth as they push
Line 1,561:		Line 922:
-	*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==		==Fracture healing==
Line 1,577:		Line 932:
	**Can get osteons to remodel through the fractured zone.		**Can get osteons to remodel through the fractured zone.
	**There is no additional tissue being formed (see secondary repair)		**There is no additional tissue being formed (see secondary repair)
-	**osteoclasts dig out a region of bone...
Line 1,583:		Line 937:
	**Useful when fracture is unstalbe; whats happening when casted		**Useful when fracture is unstalbe; whats happening when casted
	**Bone '''and cartilage''' formation occur		**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 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==		==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===		===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.		*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.		*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===		===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 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===		===Reversal===
-	*Osteoclasts leave or undergoe apoptosis.
-	*Osteoblasts arrive
	*First the osteoblasts must clean up		*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.		**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.	+	*Once they reach near the normal bone surface, the last osteoblasts become lining cells.
-	**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===		===Bone modeling===
	*This is uncoupled: osteoblastas and clasts don't work in concert.		*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===		===Bone remodeling as a cause of bone mass loss===
-	*Cause of reduced bone mass is due to two factors of bone remodeling.	+	*Estrogen inhibits bone resorption so when estrogen goes away, bone resorption increases.
-	*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===		===Diagnostics===
-	*DXA
-	**Doesn't tell you anything about bone resoprtion and generation activity.
-	*Biomarkers
-	**Does provide clast and blast activity measurements.
	===Pharma===		===Pharma===
-	*We are concerned mostly with those people who show a low density.
	*Anti-resorptives		*Anti-resorptives
-	**Here we are trying to stop clasta ctivity
	**Disphophonates		**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		**Cacitonin
-	***Not used often b/c the previous two are so successful.
	**Denosumab		**Denosumab
	***A monoclonal antibody taht targets RANK-L.		***A monoclonal antibody taht targets RANK-L.
	***Recall that RANK-L is required for dev of osteoclasts		***Recall that RANK-L is required for dev of osteoclasts
	***Acts like OPG? (what was the endogenous decoy for RANK-L)?		***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, VitD, and Phosphate==
	===Ca===		===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).		*Without enough calcium you have rickets (in kids) and osteomalacia (in adults).
	**Here the bone doesn't mineralize.		**Here the bone doesn't mineralize.
-	**DEformities occur	+	**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.		**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====		====Hypercalcemia====
-	*This is a chronic increase in Ca++.
-	*Two etiologies: primary and secondary.
	*Primary:		*Primary:
	**Elevated PTH		**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.		**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		**Treatment
	***MOdulate the parathyroid gland		***MOdulate the parathyroid gland
Line 1,778:		Line 991:
	*SEcondary		*SEcondary
-	**Three examples: toxic levels of VitD (absorb way too much ca at gut), immobilization (stimulates osteoclast activity; think space or bed-ridden), or	+	**Three examples: toxic levels of VitD, immobilization, or malignancy.
-		+	**Use antiresorptive pharma.
-	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====		====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:		*TX:
	**Increased Ca and VitD.		**Increased Ca and VitD.
Line 1,795:		Line 1,000:
	===VitD===		===VitD===
	*Calbindin is required for good CA++ absorption at the gut and VitD is a txn factor modulating txn of Calbindin.		*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.		*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.		*Ultimatley these cause osteomalacia and rickets.
	===Phosphate===		===Phosphate===
-	*An impt mineral.
	*REgulation is athe kidney		*REgulation is athe kidney
	*ABsorbed in the duodenum		*ABsorbed in the duodenum
	**Can be CA dependent or independ		**Can be CA dependent or independ
	**Also regulated by vitD.		**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		*Osteocytes secrete FGF23 and PTH from parathyroid act on kidney to reduce Na-Phosphate co-transporter
	**Causes icnreased loss of phosphate.		**Causes icnreased loss of phosphate.
		+
		+
	*When phosphate is low:		*When phosphate is low:
	**Vitd 1,25 goes up (increase resorption at the gut)		**Vitd 1,25 goes up (increase resorption at the gut)
Line 1,817:		Line 1,020:
	**vitd 1,25 is low (lower resportion at the gut)		**vitd 1,25 is low (lower resportion at the gut)
	**Increased PHT and fGF23 (increase loss at the kidney)		**Increased PHT and fGF23 (increase loss at the kidney)
-
-
-	*stopped here on 02/28/11 at 3:05PM.
-
-
-
-	*started here on 03/02/11 at 2PM.
-
-
-	*First half of alphabet in MS326 until 10:30,
-
-	====Question 1====
-	*Identify the structure between two separate lacunae.
-	**Cement line
-	*What does this structure surround?
-	**Surrounds an osteon
-	*What cell type produces it?
-	**Made by osteoblasts or maybe even the bone lining cell.
-	*What is the haversian canal and what resides within?
-	**Haversian canal
-	**Blood vessels, nerves
-	**Rarely is a cell more than 200 microns from its vascular supply.
-	**So we know that canaliculi supply the osteocytes in the osteon
-	**Osteocytes send filiopodal processes into the canaliculi
-	**Also, interstitial fluid flows through the canaliculi
-
-	====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.

---

Revision as of 01:47, 18 April 2011

Contents 1 Contraction in detail 2 Intercalated disks 3 NERVOUS SYSTEM 3.1 Astrocytes 3.2 Blood brain barrier 3.3 Microglia 3.4 PERIPHERAL NERVE 3.4.1 Slide 9 sciatic nerve dog 3.4.1.1 Slide 17 Spinal cord ganglion, mammal 4 Epithelium lecture 4.1 Tight jxn 4.2 The belt desomosome 4.3 Hemi-desmosome 4.4 Gap jxn 4.5 Basement membrane 5 Circulatory 5.1 Histology of vessels 5.2 Capillaries 5.2.1 Image examples 6 Connective Tissue 6.1 Twin study 6.2 Ground substance 6.2.1 Another componetn of ground substance 6.2.2 Integrins 6.3 Collagen 6.3.1 Fibrillar collagens 6.3.2 Type 4 collagen 6.4 Collagen synthesis 6.5 Elastic fibers 6.5.1 State 1 6.5.2 Stage 2 6.5.3 Stage 3 6.6 Loose connective tissue versus dense 7 Connective Cells 7.1 Red marrow 7.2 Erythroblasts 7.2.1 RBC membrane 7.2.1.1 Neuts 7.2.1.2 Eosinophils 7.2.1.3 Basophils 7.2.2 Agranulocytes 7.2.2.1 Thrombocytes 8 Lymphoid organs 8.1 Cell type localization in lymphoid organs 8.1.1 Thymus 8.1.1.1 Activity of the cortex and medulla 8.1.2 Encapsulated lymphoid organ organization 8.1.2.1 Spleen 8.1.2.2 =Blood flow in the spleen 9 RESPIRATORY SYSTEM 9.1 Conducting region 9.2 Respiratory region 9.3 Cells ofthe alveolar system 9.4 Blood-air barrier 9.5 Pleura 10 GI 10.1 Hard palate 10.2 Tongue 10.3 Gingiva 10.3.1 Periodontal ligament 10.4 Gut tube 10.5 Esophagus 10.6 Stomach 11 Lab 15: Digestive Tract I 11.1 A. ORAL CAVITY. 12 GI - Small intestine through anus 12.1 Stomach 12.1.1 Stomach images 12.1.2 Chief cells 12.1.2.1 Enteroendocrine cells 12.1.3 Pylorus 12.2 Small intestine 12.2.1 Glands of the si 12.3 Large intesstine 12.4 Cell turnover 13 Glands 13.1 Salivary glands 13.2 Salivary 13.2.1 Saliva 13.2.2 Secretion 13.2.3 Summary 13.3 Pancreas 13.3.1 Endocrine 13.3.2 Exocrine pancreas 13.4 Liver 13.4.1 Hepatic blood flow 13.4.2 Formation of bile 13.5 Gallbladder 14 Bone and Cartilage 14.1 Bone cells 14.1.1 Osteoclasts 14.2 Osteoblast 14.3 Osteocyte 14.3.1 Genetic profile differs from osteoblasts 14.4 Bone matrix 14.5 Tyeps of bone tissue 14.5.1 Woven bone 14.5.2 Lamellar bone 14.6 Bone anatomy 14.6.1 Haversion systems 14.6.2 Periosteum 14.6.3 Endosteum 14.7 Structures 15 Cartilage 15.1 Hyline cartilage 15.2 Fibrocartilage 15.3 Elastic cartilage 16 Joints 16.1 Synarthroses 16.2 Diarthrovidal (synovial) joints 16.2.1 Articular cartilage 16.2.2 Joint capsule 16.2.3 Osteoarthritis and Rheumatoid arthritis 17 Chondrogenesis 18 Intramembraneous bone formation 19 Endochondrial bone formation 20 Fracture healing 21 Bone remodeling 21.1 Cartoon 21.2 Activation 21.3 Reversal 21.4 Bone modeling 21.5 Bone remodeling as a cause of bone mass loss 21.6 Diagnostics 21.7 Pharma 22 Ca, VitD, and Phosphate 22.1 Ca 22.1.1 Hypercalcemia 22.1.2 Hypocalcemia 22.2 VitD 22.3 Phosphate 23 Urinary 1 23.1 Cortex and Medulla 23.2 More on macrostructure 23.3 Uniferous tubule function 23.4 Uriniferous tubule layout and embryonic development 23.5 Uritic bud and nephrogenic mesoderm interaction 23.6 Renal corpuscle structure 23.7 Forming a filter at the capillary-Bowman-space junction 23.8 Mesangial cells 23.9 The proximal tubule 23.10 Cell distinction along the PCT, LoH, and DCT 23.10.1 Cells of the PCT and PST 23.10.2 Cells of the thin descending and thin ascending tubules 23.10.3 Cells of the DST and DCT tubules 23.10.3.1 Differentiating PST and DST 23.10.3.2 PCT versus PST and DCT versus DST identification 23.10.3.3 Differentiationg PCT and DCT 23.10.4 Cells of the collecting duct 23.11 Distinguishing regions of the kidney 24 Urinary 2 24.1 Loop of Henle 24.2 More kidney superstructure 24.3 Renal vasculature 24.4 Cortex organization 24.5 Juxtuloglomerular apparatus and the renin-angiotensin pathway 24.6 Post-kidney urinary ultrastructure 24.7 Transitional epithelium of the bladder 24.8 Smooth muscle of the bladder 25 Endocrine histology 25.1 Describe the structural organization of the endocrine system 25.2 Define components of the endocrine system 25.3 Describe the embryonic origin, histological organization, and hormone secretion of the endocrine system 25.3.1 Origin, organization, and secretion of the hypothalamus 25.3.2 Origin, organization, and secretion of the pituitary gland (hypophysis) 25.3.2.1 Adenohypophysis (anterior pituitary) 25.3.2.2 Neurohypophysis (posterior pituitary) 25.3.2.3 Pituitary portal system 25.3.3 Origin, organization, and secretion of the Adrenal glands 25.3.3.1 Adrenal cortex 25.3.3.2 Adrenal medulla 25.3.4 Origin, organization, and secretion of the Pancreas 25.3.5 Origin, organization, and secretion of the Thyroid 25.3.6 Origin, organization, and secretion of the Parathyroid glands 25.3.6.1 Primary hyperparathyroidism 25.3.7 Origin, organization, and secretion of the Pineal gland 25.3.8 Origin, organization, and secretion of the Diffuse Neuro-endocrine system 25.3.8.1 Bone as an endcrine organ 26 Female reproductive histology 26.1 Ovarian cycle 26.1.1 Origin and fate of ovarian follicles 26.1.2 Ovarian anatomy 26.1.3 Ovarian follicle 26.1.4 Stages of the ovarian follicle 26.1.5 Endocrine regulation of follicle maturation 26.1.6 Ovulation 26.1.7 The corpus luteum 26.1.8 Follicular atresia 26.2 The uterine tubes 26.2.1 Layers of the oviduct 26.3 The uterus 26.3.1 Layers of the uterine wall 26.4 The uterine cycle 26.4.1 Uterine vasculature 26.4.2 Uterine endometrium 26.4.3 Histological changes in the uterine cycle 26.4.4 Uterine cervix 26.4.4.1 The ectocervix 26.5 Vagina 26.6 Mammary glands 26.6.1 Mammary glands at puberty 26.6.2 Mammary glands in pregnancy 26.6.3 Breast milk 26.6.4 Regulation of milk let-down 26.7 Summary 27 Male reproductive 27.1 Anatomy review 27.2 Seminiferous epithelium 27.3 Spermatogenesis 27.3.1 Mitosis and Meiosis 27.3.2 Spermiogenesis 27.4 Sertoli cells 27.4.1 Blood testis barrier 27.4.2 Sertoli function stimulated by FSH 27.5 Leydig cells 27.6 Segments of the male reproductive tract 27.7 Accessory glands of the male reproductive tract 27.7.1 Seminal vesicles 27.7.2 Prostate 27.7.3 Bulbourethral glands 27.8 Ejaculation sequence 28 Skin 28.1 Describe the basic histological structure of the skin 28.2 Identify the cell layers that constitute the epidermis 28.2.1 Stratum basale 28.2.2 Stratum spinosa 28.2.3 Stratum granulosmum 28.2.4 Stratum lucidum 28.2.5 Stratum corneum 28.2.6 Dermo-epidermal junction 28.3 Describe the cellular components of the epidermis and their functions 28.3.1 Keratinocytes 28.3.2 Melanocytes 28.3.3 Langerhans cells 28.3.4 Merkel cells 28.4 Describe the structural organization of the dermis 28.4.1 Papillary layer of the dermis 28.4.2 Reticular layer of the dermis 28.5 Identify other structures in the skin 28.5.1 Vessels 28.5.2 Sensory receptors 28.5.2.1 Free nerve endings 28.5.2.2 Pacinian corpuscles 28.5.2.3 Meissner's corpuscles 28.5.2.4 Ruffini's corpuscles 28.5.2.5 Sensory receptor images 28.5.3 Hair follicles 28.5.3.1 Phases of hair growth 28.5.4 Nails 28.5.5 Glands 28.5.5.1 Sebaceous glands 28.5.5.2 Sweat glands 28.6 Understand the mechanism of skin repair 28.7 Describe the histological findings in common skin diseases 28.7.1 Blistering 28.7.2 Psoraisis 28.7.3 Skin cancer 28.7.3.1 Basal cell carcinoma 28.7.3.2 Squamous cell carcinoma 28.7.3.3 Malignant melanoma 28.7.4 Griscelli syndrome 29 The eye 29.1 Optical anatomy 29.2 Wall of the eye 29.3 Eyeball function by component 29.3.1 Cornea 29.3.1.1 Epithelium of the cornea 29.3.1.2 Stroma of the cornea 29.3.1.3 Endothelium of the cornea 29.3.2 Uvea 29.3.2.1 Choroid of the uvea 29.3.2.2 Ciliary body 29.3.2.3 Iris 29.3.2.4 Eye color 29.3.3 Lens 29.3.4 Retina 29.3.4.1 Pigmented epithelium of the Retina 29.3.4.2 Neural retina

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.

Intercalated disks

• • 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.

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.

Lab 15: Digestive Tract I

A. ORAL CAVITY.

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

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.

More on macrostructure

• Medullary pyramids are separated by renal columns of Bertin.

Uniferous tubule function

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.

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.

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.

• • 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.

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 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).

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).

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

• 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 -> interlobar artery -> arcuate artery -> cortical radial artery (imagine these radiating outward from the

arc; used to be called interlobular 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 -> interlobar vein -> renal vein.

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.

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.

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.

• The neuroectoderm (floor of the diencephalon) grows caudally, forms a stalk, and remains attached to the brain tissue of origin.

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.

• 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.

Adrenal cortex

• GomiFacoRea: glomerulus-mineralocorticoids, fasciculata-corticoids, reticularis-androgens.

• 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),

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.

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.

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.

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.

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.

• 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.

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.

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.

Stages of the ovarian follicle

• 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.

• 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

• 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.

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

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:

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.

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).

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://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://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.

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

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

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

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.

The uterine cycle

• From 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.

Uterine endometrium

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

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.
  • 

• 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.

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:
  • 
• 
• 
• 

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.

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.

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.

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

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 spermatocytes
• 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).

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.

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.

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

Identify the cell layers that constitute the epidermis

• Also, the granulosa and corenum layers are thicker in "thick skin".

Stratum basale

• The cells of the basal layer are connected to the basement membrane via hemidesmosomes.

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Stratum spinosa

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.
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• • 

Stratum lucidum

• The lucidum (ironically) stains darkly.

Stratum corneum

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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.

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.

Keratinocytes

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.

Langerhans cells

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

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.

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).

Identify other structures in the skin

Vessels

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.
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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!
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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 mitochondria and are oriented perpendicular to the skin.
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Ruffini's corpuscles

• Ruffini's corpuscles are simple mechanoreceptors and have an "elongated fusiform shape".
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Sensory receptor images

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.
  • 

Phases of hair growth

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Nails

• The nail plate sit in the nail bed which is formed by the stratum basale and spinosum.

Glands

Sebaceous glands

Sweat glands

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):
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• Apocrine:
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• 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

Describe the histological findings in common skin diseases

Blistering

• Abnormalities at the epidermis-dermis junction are called bullous pemphigoid.
  • 
• Abnormalities of intercellular junctions are called pemphigus.
  • 

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.

Skin cancer

Basal cell carcinoma

Squamous cell carcinoma

Malignant melanoma

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

Wall of the eye

Eyeball function by component

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.

Epithelium of the cornea

• The epithelium of the cornea is made of stratified, squamous, non-keratinized epithelium.

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.

Endothelium of the cornea

Uvea

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.

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.

• 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.

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.

Eye color

• • 

Lens

• The epithelium on the anterior side of the lens is simple cuboidal.
• Note that the lens epithelium does not have occluding junctions.

• 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

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

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