Urinary 1 and 2

From Iusmhistology

• started here on 03/21/11.

Contents 1 Urinary 1 1.1 Cortex and Medulla 1.2 More on macrostructure 1.3 Uniferous tubule function 1.4 Uriniferous tubule layout and embryonic development 1.5 Uritic bud and nephrogenic mesoderm interaction 1.6 Renal corpuscle structure 1.7 Forming a filter at the capillary-Bowman-space junction 1.8 Mesangial cells 1.9 The proximal tubule 1.10 Cell distiction along the PCT, LoH, and DCT

Urinary 1

• The kidney has one of the most complex 3 dimensional organizations of all the organs of the body.
• We will study the kidney incrementally, beginning with the uriniferous tubule.
  • We will study some simpler kidneys that contain only one papillary, called "unipapillary kidneys".

Cortex and Medulla

• The kidney has two major regions: the cortex on the outside and the medulla on the inside.
• The pelvis is the sinus area of the kidney that is "sub-medulla" and forms the collecting area for urine before it enters the ureter.
• Urine is produced by lobes which contain a single renal papillum which dumps urine into the pelvis which dumps into the ureter.
  • Small mammals often have only one lobe and therefore one renal papillum.
  • Humans have multiple lobes and therefore multiple renal papilla.
• In unipapillary kidneys, the uriniferous tubules run all the way from the cortex to the papillum-pelvic border.

More on macrostructure

• Each uriniferous tubule is situated in one of the many medullary rays and medullary pyramids found in humans.
  • The cortical region contains the glomeruli and is called the medullary ray.
  • The medullary area contains the vasa recta, the loop of Henle, and the collecting duct.
• Medullary pyramids are separated by renal columns of Bertin.
• The renal pelvis is the area where the ureter begins to form from the sinus of the kidney.

Uniferous tubule function

• The uriniferous tubule is made up of epithelial cells.
• The tubule is surrounded by two sets of capillaries:
  • The glomerular capillaries are within the Bowman's capsule in the cortex.
  • The peritubular capillaries are within the medulla, along the length of the loop of Henle and the collecting duct.
• The renal corpuscle is the glomerulus, Bowman's capsule, and the glomerular capillaries.
  • The renal corpuscle's function is to filter the plasma passing through the glomerular capillaries.
• The nephron and collecting describes everything other than the renal corpuscle.
  • The nephron and collecting duct serve to secrete waste products and reabsorb nutrients to / from the filtrate.

Uriniferous tubule layout and embryonic development

• Though we draw the uriniferous tubule as a simple, linear tract, it is rarely this simple in final 3D form.
• It is important to understand embryonic development to understand why the uriniferous tubule takes its certain and functional 3D form.
• For proper functioning, it is critical that certain sections of the uriniferous tubule lie next to one another.

• The first form of a plasma filtering mechanism in the developing human embryo is called the mesonephric kidneys.
• Mesonephric kidneys reach their maximum size at 8 weeks and then undergo a large change.
• Parts of the mesonephric kidneys persist in men to form:
  • the efferent ductules,
  • the epididymis,
  • the ductus deferens, and
  • the ejaculatory duct.
• The cloaca is an early developing orifice that serves to excrete feces and urine.
  • The cloaca is common between placental mammals, birds, amphibians, etc.
  • The cloaca is retained by birds, amphibians, and reptiles.
  • The cloaca in mammals divides and conributes to the anus and the urethra / vagina.

• The early plasma filtering structure is divided into two sections: the mesonephros and the metanephros.
• The metanephros gives rise to the permanent kidneys.
  • The metanephros contains the metanephric mesenchyme and the uritic bud.
  • The uritic bud and the metanephric mesenchyme are both composed of epithelial cells.
• The uritic bud grows up into the nephrogenic mesoderm which is part of the metanephros.

Uritic bud and nephrogenic mesoderm interaction

• The uritic bud grows into the nephrogenic mesoderm to form the mature uriniferous tubules.
• The interaction between the uritic bud and the nephrogenic mesoderm is called reciprocal induction.
  • Reciprocal induction: "... tissues causing changes in each other due to signals and receptors in each" per this paper

• 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.
• 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).
  • 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.

Renal corpuscle structure

• The renal corpuscle demonstrates the unique development of the uriniferous tubule by the way the podocytes surround the glomerular capillaries.
  • Note that podocytes are a type of epithelial cell.
  • Capillaries are a type of endothelial cell.
• We call the glomerulus the glomerular tuft before fully developed.
• Within the capillaries as they develop within the glomerular tuft, there is connective tissue holding the capillaries in place.
• Bowman's space is the epithelial tract that surrounds the tuft of capillaries.
  • Note that this place forms a complex structure surrounding the many, convoluted, cross-connected capillaries within.

• There are many cell types and structures of the renal corpuscle; each cell type has a specific location and function.
• The afferent arteriole is made of endothelial cells and brings blood to the glomerular capillaries.
• The efferent arteriole is made of endothelial cells and takes blood away from the glomerular capillaries (to the peritubular capillaries).
• The Bowman's capsule is made of epithelial cells and surrounds the glomerular capillaries, forming the Bowman's space beween the Bowman's capsule and the walls of the glomerular capillaries.
  • The inside layer of the Bowmans capsule covers the convoluted capillaries and is called the visceral layer; the parietal layer is the outside layer that forms the outer barrier of the glomerulus and is continuous with the epithelium of the PCT.
  • The Bowman's space is the location into which filtrate is first formed by being pressed out of the plasma by hydrostatic forces (primarily, but also including colloid osmotic pressures).
• The epithelial cells of the Bowman's capsule are continuous with the epithelial cells that make up the proximal convoluted tubule which carries filtrate.
• The distal convoluted tubule (which is, like the PCT, made up of epithelial cells) passes by the afferent arteriole along side the glomerulus.
  • The DCT has specialized cells called 'macula densa cells on the surface that is closest to the afferent arteriole.
  • Macula densa cells release signals PGE2 to cause the afferent arteriole to vasodilate and ATP to cause the afferent arteriole to constrict.
  • Macula densa cells are more columnar, stain darker, and have rounder nuclei than the endothelail cells of the DCT.
• Juxtaglomerular cells (also called granular cells) are endothelial cells of the afferent arteriole that contain granules of renin.
  • Granular cells (AKA juxtaglomerular cells) have a large, flattened nucleus, that is more prominent than the nucleus of lacis (extraglomerular mesangial) cells.
  • Granular cells release their renin upon PGE2 binding their EP4 receptor.
  • Recall that renin will activate angiotensinogen leading to angiotensin 2 and systemic vasodilation.
• Lacis cells (also called extraglomerular mesangial cells) hold the DCT, the afferent arteriole, and the glomerulus together.
  • Extraglomerular mesangial cells may also have some functioning in modifying the signals released by the macula densa cells as they travel to the granular / endothelial cells of the afferent arteriole.
  • Lacis cells (extraglomerular mesangial cells) are found between the macula densa cells and the afferent arteriole endothelial cells.
  • Lacis cells have a lighter stain and less prominent nucleus as compared to granular (juxtaglomerular) cells.
    • This makes sense because granular cells will have granules full of the protein renin.
  • Extraglomerular mesangial cells are found between the convoluted capillaries, too, and serve to hold the loops in their structure.
    • In this case, the mesangial cells are located within the basement membrane.
  • Lacis cells can send processes into the lumen of the capillaries between the endothelial cells.

Forming a filter at the capillary-Bowman-space junction

• There are three levels of filtration at the capillary-Bowman-space junction.
• The filtrate must first get through the endothelium of the capillary, then through the basement membrane, and then through the feet of podocytes.

• The endothelium of glomerular capillaries is fenestrated to allow only very small proteins and smaller molecules through.

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

• Podocytes are a type of epithelial cell that provide the finest level of filtration of the plasma as it crosses into the Bowman space.
  • Podocytes project feet that sit on the outside (that is, the Bowman space side) of the capillaries.

• 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.

Mesangial cells

• Recall that mesangial cells reside between capillaries within the basement membrane.
• Mesangial cells may modulate capillary dilation and contraction and thus be a part of glomerular blood flow.
• Mesangial cells may also act as phagocytes within the basement membrane of the glomerulus.

The proximal tubule

• The proximal tubule's primary function is reabsoprtion.
• The proximal tubule is characterized by uniform, columnar-low-columnar, continuous epithelial cells with large 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 tubule is made up of the proximal convoluted tubule and then then proximal straight tubule' which then proceeds into the descending loop of Henle.
  • The proximal straight tubule continues through the outer stripe of the outer medulla.
  • "Straight segments ... terminate at a remarkably uniform level ... that establishes the boundary between the inner and outer stripes of the outer ... medulla." per wikipedia

Cell distiction 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.

• Cells of the PCT and thick descending loop:
  • There are only epithelial cells in the PCT and thick descending loop.
  • Recall that the PCT reabsorbs 70% of the filtrate; therefore it makes sense that the cells of the PCT and thick descending tubule are the only cells with a brush border.
  • Cells of the PCT and thick descending tubule also have nuclei that are spaced far apart.
  • PCT / thick descending tubule epithelial cells stain very pink.
  • PCT / thick descending tubule cells are interdigitated.

• Cells of the thin descending and thin ascending tubules:
  • There are only epithelial cells in the thin descending and ascending tubules.
  • Recall that the descending loop is passively 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 thick ascending and DCT tubules:
  • There are three cell types in the thick ascending and DCT tubules: epithelial cells, macula densa cells, and principal cells.
  • Recall that the thick ascending tubule and the DCT are the hormone-responsive regions with many ion transporters to reabsorb Na and Cl in exchange for K.
  • The thick ascending tubule is called the "diluting segment" of the nephron because solutes are removed from the filtrate and the epithelium is not very permeable to water, thus making the filtrate more dilute as solutes are reabsorbed and water cannot follow.
  • The DCT is considered part of the LoH.
  • Epithelial cells of the thick ascending tubule and DCT need lots of protein to facilitate ion transport and so it makes sense that thick ascending epithelium and DCT epithelium have lots of mitochondria.
  • Epithelial cells of the thick ascending tubules and the DCT have apical nuclei that bulge outward (perhaps because of the mt that are pushing them apically).
  • Thick descending and thick ascending can be differentiated by their stain and the relative spacing of their nuclei:
    • Thick descending epithelium stain darker than thick ascending epithelium.
    • Thick descending epithelium has wider separation between nuclei than thick ascending epithelium.
  • Recall that epithelial cells of the DCT will include macula densa cells.
    • Macula densa cells stain darker than other epithelial cells and are more columnar.
    • Macula densa cells are found at the vascular pole of the glomerulus, near the endothelial cells of the afferent arteriole.
  • The DCT is the first site of principal cells.

• Cells of the collecting duct:
  • There are two types of epithelial cells in the collecting duct: epithelial cells, principal cells and intercalated cells.
  • Recall that the collecting duct's function is to reabsorb water--to concentrate the urine.
  • Epithelial cells of the collecting duct are characterized by large, weakly staining (even clear) cells that bulge into the lumen.
  • Epithelial cells of the collecting duct have clear distinctions between each cell and have nuclei that do not bulge (like PCT / thick ascending tubule epithelial cells).
    • Principal cells are hormonally controlled for water reabsorption and are the major site of potassium regulation.
    • Intercalated cells stain darkly 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 '.
***The last section of the inner medullary collecting duct is called the 

• stopped here on 03/21/11.