Renal -1

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H & E stain of a pig kidney showing the demarcations of the different lobes. There are approximately 18 lobes in an adult human kidney but they are only demarcated in the fetus. Know which regions are associated with higher osmolarity (medulla vs. cortex) and where the papillae are (at the base).

Hint 1

The kidneys are situated retroperitoneally on either side of the posterior abdominal wall. In an adult, the kidneys are reddish-brown, bean-shaped organs, each weighing approximately 150 grams. Each kidney is surrounded by a dense connective tissue capsule and has a hilar indentation on one side. At the hilar region, renal vessels, lymphatics, and nerves enter and leave the kidney, and the ureter exits the kidney.

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Low magnification view of a unilobular rat kidney. See the difference between the cortex (C),
outer medulla (OS and IS), and the inner medulla (IM). Again, which parts of the nephron are found in
each location?

Hint 2

Netter drawings showing the difference between a juxtamedullary nephron and a superficial nephron.

Know what segments are found in each location:
CORTEX
1. renal corpuscles
2. convoluted tubules
3. collecting ducts
4. medullary rays

OUTER MEDULLA
1. thick segments of LOH
2. part of the descending thin segments
3. collecting ducts

INNER MEDULLA
1. thin segments of LOH
2. collecting ducts
3. vasa recta

The outer medulla has an inner and outer stripe but you are NOT responsible for knowing the difference between them. Note, medullary rays are made of thick ascending and thick descending segments as well as collecting ducts.

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This slides shows the renal vasculature. The balls are glomeruli (remember there are 1 million in each kidney). This is the location of filtration. You can also see the interlobular artery branching to
intralobular branches and then afferent and efferent arterioles. Also, note the peritubular capillary plexus.

Hint 3

Glomerular filtrate passes across the glomerular wall -->
capsular space of Bowman --> opening of urinary pole of the renal corpuscle -->
uriniferous tubules.

The first segment of the uriniferous tubule is termed the PROXIMAL TUBULE. It is within the proximal tubule that most of the glomerular filtrate is reabsorbed back into a rich PERITIBULAR CAPPILARY PLEXUS which surrounds these tubules. The first portion of the proximal tubule follows a highly convoluted course within the cortical substance of the kidney, and has therefore been termed the PROXIMAL CONVOLUTED TUBULE/ (PARS CONVOLUTA).

The portion of the proximal tubule that descends from the cortex into the outer stripe of the outer medulla has been termed the DESCENDING PROXIMAL TUBULE (AKA PARS RECTA/ DESCENDING THICK SEGMENT OF THE LOOP OF HENLE/ STRAIGHT SEGMENT OF THE PROXIMAL TUBULE (S3).

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S1-S3 all have microvillus brush border.
macula densa
parietal epithelial
proximal tubules -contain debris in lumen
urinary pole

A periodic acid shift stain of the renal cortex containing a renal corpuscle. This basically
shows the carbohydrate-rich glycocalyx of the brush boarder (pinkish) and debris in the lumen of the proximal tubule (due to ruptured cells and cellular debris that result from the fixation process). The urinary pole is at the bottom of the renal corpuscle and the vascular pole is approximately 180 degrees away. Also, note the afferent arteriole contains renin granules and marks the macula densa a component of the Juxtaglomerular apparatus, while the efferent arteriole does not (this can help distinguish them). This is seen as a cluster of nuclei at the top of the slide.

Hint 4

The cuboidal cells that make up the wall of the PROXIMAL CONVOLUTED tubule have:
~elaborate basolateral folds,
~numerous mitochondria,
~an extensive lysosomal system,
~and a microvillous brush border coated with a rich glycocalyx.


Based on differences in fine structure, histochemistry and function, the proximal convoluted tubules have been further subdivided into two segments. Comparing FIRST SEGMENT OF THE PROXIMAL CONVOLUTED TUBULE (S1) to the the SECOND SEGMENT OF THE PROXIMAL TUBULE (S2), we see that S1 has more:
~TALLER cells
~TALLER microvillous BRUSH BORDER
~MORE elaborate intercellular INTERDIGITATION,
~MORE MITOCHONDRIA,
~LESS prominent LYSOSOMES

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Back 5

Dr. Andrews said during his lecture: DON’T WORRY ABOUT THIS SLIDE

A view of the renal cortex containing a renal corpuscle.
A = Nucleus of a podocyte on the inner part of Bowman’s capsule.
B = Distal Tubule
C = Macula Densa (this is really not clear)
D = Proximal tubule
E = Ascending Segment (difficult to determine this on this slide)
F = Distal tubules
G =parietal epithelium of Bowman’s capsule
H = Urinary pole

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This slide is much clearer and could show up on a test.
A = Vascular pole.
B = Parietal
epithelium (cells are flat).
C = Urinary Pole.
D = Visceral Epithelium (Nucleus of podocyte)
E = Peritubular Capillaries.
F = Proximal Tubules.
The space between the parietal and visceral epithelium is called Bowman’s space or Urinary space.
The macula densa is near A at the top of the slide.

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to left= proximal tubles
bottom= renal corpuscule

A close up H&E stain of the macula densa. It means dark spot and it stains darkly because of the nuclei. It is adjacent to the glomerulus.

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~~IMPORTANT SLIDE ~~
(bottom is vascular pole, can’t see urinary pole )
PE – parietal epithelium
US- urinary space
Ef – efferent arteriole
Af – afferent arteriole – can see renin granules in walls of afferent arteriole
En – endothelial cell
Po- podocytes make up visceral layer
MC – mesangial cells
Pca – peritubular capillaries
Fm – filtration membrane
MD – macula densa

RED ARROWS: indicating the place at the vascular pole where simple squamous cells termed the parietal epithelial layer of bowman’s capsule, reflect to form the visceral layer of bowman’s capsule composed of podocytes.

Hint 8

Glomerular capillaries are unique in being lined by a GLOMERULAR ENDOTHELIUM perforated by numerous open fenestrations.

These endothelial loops are surrounded by a thick basal lamina termed the GLOMERULAR BASEMENT MEMBRANE (i.e. 240 to 340 nm thick in humans), and an epithelium termed the VISCERAL LAYER OF BOWMAN'S CAPSULE.

The specialized cells comprising this visceral layer are termed PODOCYTES (podo= greek for foot)

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PS1: proximal tube S1 – can see microvillous brush border and abundance of mitochondria.
LITTLE ARROW: RENIN granules
BIG ARROW: Extra-glomerular mesangial cells
Md: macula densa
Aa: Afferent a.
Ea: Efferent a.

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Another TEM of the renal corpuscle.
BS = Bowman’s space.
P = Podocytes.
C = capillary lumen.
V = Vascular pole.

Between the two large arrows is the thin parietal epithelium.

Between the capillaries are mesangial cells. You can also see the macula densa on the bottom right. MASCULA DENSA IS ONLY ON THE VASCULAR POLE!! neVER SEE IT ON URINARY POLE

Hint 10

THE JUXTAGLOMERULAR APPARATUS

As the STRAIGHT DISTAL ASCENDING SEGMENT goes back into the cortex, it passes between the afferent and efferent arterioles of the renal corpuscle from which it arose. The EXTRAGLOMERULAR MESANGIUM. (or LACIS CELL because they are surrounded by a lot of extracellular matrix… "lacis" or network.) is the compact cushion of small cells that separates the distal tubule from the renal corpuscle at this site. They look kinda like the mesangial cells in the glomerulus.
The cells in the wall of the DISTAL TUBULE in this region become thinner, sometimes taller, and the DARK STAINGING nuclei appear clumped to form the MACULA DENSA (Greek= dense spot).

Smooth muscle cells in the wall of the AFFERENT ARTERIOLE adjacent to the macula densa are modified into cells that synthesize, store (in membrane-bound GRANULES), and secrete the hormone RENIN. JUXTAGLOMERULAR CELLS= RENIN PRODUCING CELLS.

juxtaglomerular cells + macula densa = JUXTAGLOMERULAR APPARATUS.

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TEM of a podocyte.
Np = Podocyte nucleus.
BS = Bowman’s Space.
M= major processes of the podocyte.
F = foot processes.
Ms = Mesangial cell.
Ne = Endothelial cell nucleus.
R = RBC in the capillary space (C).

REMEMBER PORE ARE NOT SPANNED BY DIAPHRAMS. The filtration slits are...

Hint 11

In addition to glomerular endothelial cells and glomerular podocytes, the glomerulus contains a third cell type termed the mesangium. Mesangial cells are most prominent at the vascular pole of the glomerulus where tree-like ramifications of unique population of cells radiate out between the glomerular
endothelium loops. Mesangial cells send cell processes (pseudopodia) between endothelial cells and can
phagocytose material that may accumulate in the glomerular basement membrane. Mesangial cells also produce a significant amount of extracellular amorphous basement membrane-like material known as mesangial matrix.

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TEM of the filtration membrane or glomerular wall across which, filtration occurs. The lumen of the urinary space is on the top and the lumen of the capillary space is on the bottom. The top blobs are the foot processes with the plasma membrane surrounding them and the basement membrane beneath (3 parts – lamina rara interna and externa with the lamina densa in the middle). The endothelium (capillary lining) is fenestrated and contains NO diaphragms. This facilitates filtration.

The fuzzy looking coat on the foot processes is the glycocalyx, which has filtration slits WITH diaphragms. The foot processes change their shape to regulate flow across the membrane and during different pathological processes the foot processes can actually retract and be lost. EM is important in the diagnosis of this kind of pathology.

Hint 12

Morphology of the Glomerular Wall

The possible barriers to the passage of plasma protein the size of albumin across the glomerular wall have been the subjects of considerable investigation. In passing across the glomerular wall, the glomerular filtrate must first pass across the highly fenestrated glomerular endothelium. Since glomerular endothelial fenestrations are large (20 to over 100 nm in diameter) and are not spanned by diaphragms, they do not restrict molecules such as serum albumen. After passing through the endothelial pores, the
glomerular filtrate must pass through the thick glomerular basement membrane (GBM). This layer of basement membrane consists of three layers that differ in their electron densities. The innermost layer is termed the LAMINA RARA INTERNA, the middle layer the LAMINA DENSA, and the outer layer the LAMINA RARA EXTERNA.

In addition to acting as a mechanical barrier, anionic sites (i.e., heparin sulfate) distributed along the lamina rara interna and externa may represent an electrostatic barrier that repels negatively charged molecules (such as serum albumin), thereby preventing them from passing into the glomerular filtrate.
Having passed through the thick GBM, the filtrate must pass through the filtration slits between adjacent podocyte foot processes. The filtration slit, however, is spanned by a slit diaphragm having a substructure consisting of rectangular-shaped pores that appear to be just small enough to prevent serum albumen from passing into the capsular space of Bowman. The filtration slits and glomerular podocytes are also covered with a prominent sialic acid rich glycocalyx. This glycocalyx is also negatively charged and is believed to cause repulsion of adjacent foot processes, thereby maintaining open filtration slits. After passing across the filtration slits, the glomerular filtrate passes into the capsular space of Bowman and out the urinary pole of the renal corpuscle. Size, shape and charge are all factors that determine whether or not molecules can pass across the glomerular wall. Smaller, more slender, and positively charged molecules can pass across the glomerular wall easier than larger, globular, more negatively charged molecules. Also, disruption of blood flow through the glomerular wall. Smaller, more slender, and positively charged molecules can pass across the glomerular wall easier than larger, globular, more negatively charged molecules. Also, disruption of blood flow through the glomerular capillaries will significantly increase the permeability of the glomerular wall to large molecules.

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Low magnification Scanning EM of the kidney showing the cortex (C) and Medulla (M) with the large arrows pointing at medullary rays in the cortex. The small arrows are pointing at glomeruli.

Remember that tubules in the medulla are mostly straight while tubules in the cortex are convoluted (twisted).

NOTE MEDULLARY RAYS CONSIST OF:
ASCENDING & DESCENDING THICK SEGMENTS OF THE LOOPS OF HENLE & COLLECTING DUCTS.

Hint 13

If a kidney is cut in cross section, one can distinguish an outer, granular CORTEX from an inner,
more striated appearing MEDULLA. Numerous small bands of medullary tissue project into the cortical substance to form what are termed MEDULLARY RAYS. The medullary substance is separated into pyramidal-like
regions by columns of cortical substance termed the renal columns. Each medullary pyramid plus the overlying cortical substance constitutes a KIDNEY LOBE. In man, there may be anywhere from 8 to 18 lobes
comprising each kidney. In the human fetus, these lobes are demarcated by indentations on the outermost surface of the kidney. In adults, however, such surface indentations are usually lost. The tips of the medullary pyramids, which are termed PAPILLAE, project into funnel-like structures termed CAYLYCES (from
the Greek word Kalyx meaning cup), which arise from the renal pelvis (an expanded portion of the ureter) and wrap snugly around the cone-shaped papillae.

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SEM of the renal corpuscle showing Bowman’s Space (BS),Vascular pole (V), and the thin parietal epithelium between the arrows.

Hint 14

The Renal Corpuscle
The RENAL CORPUSCLE is a spherical structure, approximately 200 microns in diameter, which is
specialized for filtering solute from the blood. The filtering unit is composed of:
(1) THE GLOMERULUS (a highly convoluted capillary tuft)
(2) two layer of cells termed BOWMAN'S CAPSULE.

The glomerular capillary tufts arise from AFFERENT ARTERIOLES which branch off from INTERLOBULAR ARTERIES, as the latter course through medullary rays into the cortical substance of the kidney. Each afferent arteriole divides into capillary bundles that make up the glomerular tuft. Blood exits the glomerular capillaries by way of an EFFERENT ARTERIOLE rather than a venule. Why? (ateriole= permitting smooth
muscle in the walls of the afferent and efferent arterioles to exert control over hydrostatic pressure within the glomerular capillary loops!!)

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SEM of a podocyte (they don’t normally look this nice but this cell underwent compensatory
hypertrophy).
N= the nucleus,
M= the major processes and
F= the foot processes coming off at right angles forming filtration slits.

Hint 15

Each podocyte consists of a central nucleated region from which large branching major processes arise and wrap around underlying glomerular capillary loops. Arising at nearly right angles from the podocyte major processes are numerous, smaller and more uniformly shaped processes termed foot processes or pedicels. Foot processes from one podocyte always interdigitate with foot processes from other
podocytes and are separated from each other by a space termed the filtration slit (approximately 20-40
nm). These filtration slits represent a morphological barrier to solute passing across the glomerular wall.
There is evidence to suggest that contractile proteins (i.e. actin and myosin) within foot processes can
cause these processes to change in shape and thereby regulate the size of intervening filtration slits and
solute flow across the glomerular wall. In the region of the renal corpuscle, where the afferent and
efferent arterioles enter and leave the glomerulus (termed the vascular pole of the renal corpuscle),
visceral epithelium podocytes reflect back from the glomerular vessels and transform into a layer of simple squamous cells termed the parietal epithelial layer of Bowman's capsule. This thin parietal epithelium forms the outermost layer of the renal corpuscle and is separated from the podocyte covered
glomerular capillary tuft by the capsular space of Bowman. At a point approximately opposite to the vascular pole of the renal corpuscle is the urinary pole of the renal corpuscle where the parietal
epithelium forms an opening leading into the uriniferous tubules.

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Section of uriniferous tubules in the renal cortex. There are three proximal convoluted tubules
(top, left, and bottom) containing a prominent microvillus brush border, and debris in the lumen. In the middle is a distal tubule or thick limb and on the right is a collecting duct. Note that these structures do not have a brush boarder and have straight intercellular borders.

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Another section showing the difference between proximal convoluted tubules (periphery of the slide) and distal convoluted tubules (center of slide). Again, the PCT contains a microvillus brush border, debris in the lumen, is darker staining (because of the organelles in the cytoplasm), and the nuclei are farther apart. The DCT is the opposite.

Hint 17

The proximal tubules are very sensitive to ischemia and will swell within seconds following an interruption of blood flow to the kidneys. This swelling results in the narrowing of the tubule
lumens, focal rupturing of the apical cell plasmalemma, and extrusions of cytoplasmic debris into the tubule lumens. Therefore, unless care is taken to fix proximal tubules segments in such a way as to avoid the foregoing insults (i.e., by vascular perfusion or dripping fixative on the living kidney), these tubules will exhibit numerous artifacts that are otherwise not seen in the normal living tubules.

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AV= Apical Vesicle
FE= WAll of proximal tubule

TEM of the uriniferous tubules in the cortex using vascular perfusion fixation, which prevents
cellular damage in the PCT and thus debris from collecting in the lumen. Again, note the microvillus
brush boarder in the proximal tubules, and the basolateral folds. These cells have complex interdigitations in their boarders and many absorption vesicles.

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TEM of the second section of the proximal convoluted tubule (PS2) containing lots of lysosomes in the cytoplasm as well as mitochondria.

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Shows the transition between the thick and thin descending segments at the large arrows. This marks the margin of the inner and outer stripe of the outer medulla. You can also see ascending thick segments.

Hint 20

The Loop of Henle
From the proximal convoluted tubules, each uriniferous tubule descends to variable depths within the medullary substance, takes a hairpin turn, and ascends again to the same renal corpuscle from which it arose. This loop is called the LOOP OF HENLE. The loop of Henle is subdivided into four basic morphological segments:
1.DESCENDING THICK SEGMENT (descending proximal tubule/ straight segment of the proximal tubule)
2.DESCENDING THIN SEGMENT
3.ASCENDING THIN SEGMENT
4.ASCENDING THICK SEGMENT (ascending/straight distal tubule)

The initial portion of the descending segment of the loop of Henle is lined by cells identical to those that line the second
segment of the proximal tubule (i.e., the S2 segment). This descending S2 segment, however, abruptly changes to cells characteristic of what has been termed the THIRD SEGMENT OF THE PROXIMAL TUBULE (S3) that has:
~relatively STRAIGHT intercellular BORDERS
~FEWER mitochondria,
~***BUT they still possess a prominent microvillous BRUSH BORDER

The THIN segments are both comprised of SIMPLE SQUAMOUS CELLS. Differences in intercellular junctions and degree of cellular interdigitation have been described along the length of the thin segments of the loop of Henle.

The ASCENDING THICK SEGMENT starts out as an ABRUPT transition from the ascending thin segment to CUBOIDAL cells with elaborate basolateral folds and numerous mitochondria. As the ascending thick segment approaches the cortex, however, the lining cells transform to lower simple cuboidal epithelium.

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Shows the same transition. The large arrow points to a descending thick section changing into a thin segment at the small arrow, as part of the LOH. You can also see the ascending distal tubule (ADT with lots of mitochondria), third section of the proximal convoluted tubule (PS3 with prominent brush boarder) and the vasa recta (VR).

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Shows the inner stripe of the outer medulla (again we’re not responsible for the distinction between the inner and outer stripe). A shows the vasa recta with blood in the lumen. B shows the ascending thick segments. C shows the collecting ducts and D shows the thin segments of the LOH.

Hint 22

Tubule Heterogeneity
Different segments of the uriniferous tubules are:
~morphologically DISTINCT
~confined to DIFFERENT REGIONS of the kidneys
~perform DIFFERENT FUNCTIONS with respect to modifying the glomerular filtrate
~RESPOND QUITE DIFFERENTLY to various physiological and pharmacological stimulations.

It is not surprising, therefore, that different segments of the nephron respond quite differently to renal insults.
For example, the NEPHROTOXIC SUBSTANCE:
MERCURY is specifically toxic to the S2 segments of the proximal tubule
CHEMOTHERAPEUTIC drug CIS-PLATINUM is specifically toxic to the S3 proximal tubule segment (13).

An understanding of the different uriniferous tubule segments is therefore essential to understanding both the physiology and pathology of the kidney.

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A view of the transition from the ascending thin segments to the ascending thick segments of the LOH. Note the difference between the flattened squamous cells and the cuboidal cells. This change also reflects their different functions.

Green arrows indicate transition from ascending thin segment (simple squamous cells) to ascending thick segment (cuboidal cells)

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In this view of the inner stripe of the outer medulla you can see the collecting ducts (CD) with principal cells and intercalated cells. The latter contain microplicae on their surfaces and many cytoplasmic organelles, which make them stain darker.

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THIS IS DEFINITELY ON EXAM

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Know this slide! Dr. Andrews said not so subtly that it will be tested!! This slide shows a
medullary ray. It has 3 parts – the ascending thick, the descending thick, and collecting duct. The
medullary ray is found in the cortex with the superficial nephrons. The top structure here is the collecting duct with straight boarders between pail staining cells. The middle structure is the ascending thick segment with a clear lumen and shorter cells. Finally, the last structure is the descending thick segment or S3 part of the proximal tubule lined by a microvillus brush boarder and containing debris in
the lumen.THERE ARE NO THIN SEGMENTS HERE SINCE THIS IS IN THE CORTEX!!!!!!!!!

You should what is found in a medullary ray.

NOTE::: MEDULLARY RAYS CONSIST OF:
ASCENDING and DESCENDING THICK SEGMENTS OF THE LOOPS OF HENLE & COLLECTING DUCTS. (no thin segments!!)

Hint 25

The Connecting Segment and the Collecting Ducts
As the distal convoluted tubules merge with the collecting ducts, there is a short segment of tubule, termed the CONNECTING SEGMENT, which appears to represent a gradual transition from cells that characterize the distal tubule to cells that characterize the COLLECTING DUCTS. The collecting ducts have a different embryological origin than the rest of the uriniferous tubules and are often not considered to be part of the nephron. The cortical collecting ducts receive many branches from the distal tubules as they
pass through the medullary rays. There are two cell types that characterize the cortical collecting ducts.
1.PRINCIPAL CELL TYPE
~relatively straight intercellular borders
~paucity(scarcity) of cytoplasmic organelles
~very few apical surface microprojections,
~ one or two cilia projecting into the tubule lumen.
2. INTERCALATED CELL/ DARK CELL (surrounded by principal cell type & stains darker at both the light and EM)
~many more cytoplasmic organelles
~more electron-dense cytoplasm,
~free surface characterized by numerous free surface microprojections (either microvilli or microplicae)
~lack of rudimentary cilia.

Unlike the uriniferous tubules, the collecting ducts merge with each other in the inner medulla to form larger and larger ducts. As they descend into the papillary region of the inner medulla, the collecting ducts have very large lumens, are lined by tall columnar cells, and are often termed PAPILLARY DUCTS (of Bellini).
DARK INTERCALATED CELLS ARE USUALLY NOT FOUND IN PAPILLARY COLLECTING DUCTS.
Newly formed urine flows from 18-24 small crevice-like openings of the papillary ducts at the papillae tip (area cribosa= latin for sieve).

NOTE::: MEDULLARY RAYS CONSIST OF:
ASCENDING & DESCENDING THICK SEGMENTS OF THE LOOPS OF HENLE & COLLECTING DUCTS.

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A view of the inner medulla containing collecting ducts (straight borders), thin segments of the LOH, and vasa recta filled with blood.

Hint 26

Nephron Heterogeneity

There are at least three populations of nephrons within the kidney based on their location in the cortex. These are termed the SUPERFICIAL, MIDCORTICAL, AND JUXTAMEDULLARY NEPHRONS.

THE JUXTAMEDULLARY NEPHRONS, (~ only 15% of the renal corpuscles) are especially important in that:
~ they are LARGER,
~ LOOPS OF HENLE considerably LONGER than other nephrons,
~ EFFERENT ARTERIOLES are unusually LARGE and give rise to the VASA RECTA which supplies the MEDULLARY SUBSTANCE with its circulation.

SHORTER LOOPS OF HENLE ARISE FROM MORE SUPERFICIAL RENAL CORPUSCLES.
~may form the BENDS OF THEIR HAIRPIN LOOPS at ANY LEVEL IN THE OUTER MEDULLA or even within the CORTEX.
There is an increasing amount of evidence to indicate that different populations of nephrons can respond differently to chronic and acute renal insults.

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Another excellent slide for test question. HINT HINT

Back 27

Collecting ducts in the inner medulla have discrete intercellular boarders. You can also see vasa recta with blood in them, and thin segments without blood (ascending and descending thin look identical with a light microscope).

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Collecting ducts in the inner medulla with more thin segments and vasa recta.

Hint 28

CIRCULATION, LYMPHATICS, AND NERVES IN THE KIDNEY

In proportion to their weight, the kidneys receive more blood than any other organ in the body. The renal artery that supplies the kidney sends branches termed INTERLOBAR ARTERIES between the kidney lobes. At the cortical-medullary junction, these interlobar arteries bend to form ARCUATE ARTERIES (because of their arched configuration) that then send numerous smaller branches into the medullary rays substance as INTERLOBULAR ARTERIES. The interlobular arteries in turn give off small AFFERENT ARTERIOLES, each of which will give rise to a compact tuft of glomerular capillaries that is termed the GLOMERULUS. The efferent arterioles emerging from the glomerulus give rise to an extensive capillary plexus (termed the VASA CONVOLUTA) that surrounds the cortical tubules. In the living kidney, the uriniferous tubules appear to be surrounded by a sea of rapidly flowing blood, thereby facilitating the exchange between the tubules and the circulation. Efferent arterioles from juxtamedullary glomeruli, however, give rise to vessels which
course down into the medulla as the DESCENDING VASA RECTA. As the vasa recta descends into the medulla it gives off capillary plexuses to the inner and outer stripes of the outer medulla and to the inner medulla. The blood from the capillary plexuses in the medulla then returns to the cortex by merging with vessels of the ASCENDING VASA RECTA. This system of capillaries is responsible for supplying blood flow to the medulla and for establishing a COUNTERCURRENT EXCHANGE SYSTEM important for maintaining the osmotic gradient within the medullary pyramid. The capillaries comprising the vasa recta and the vasa convoluta are all of the fenestrated variety, with the fenestrations spanned by diaphragms. The arterial circulation to the cortex and medulla returns through companion veins that run along side the arterial supply (i.e., INTERLOBULAR, ARCUATE, and INTERLOBAR VEINS). In addition to blood flow, the cortical substance is supplied with subcapsular and deeper cortical lymphatic drainage. The intrarenal lymphatics are primarily distributed along the interlobular and arcuate arteries.

The kidney is abundantly supplied with nerves derived mainly from the CELIAC PLEXUS and from the THORACIC and LUMBAR SPLANCHIC NERVES. Numerous studies have demonstrated an effect of nervous innervation on kidney function. The nerves have been shown to establish neuroeffector junctions with renal vessels and the proximal and distal tubules. Although nervous innervation is believed to play an important role in regulating the degree of constriction of renal glomerular efferent and afferent arterioles, the role of nervous innervation in the uriniferous tubules has not yet been fully elucidated.

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Papillary region with taller principle cells. Here two large papillary ducts are merging.

Hint 29

The renal cortex contains a paucity (scarcity) of interstitial connective tissue, most of which is associated with the renal vessels.
The GLOMERULUS, the PARIETAL EPITHELIUM and all the URINIFEROUS TUBULES are surrounded by prominent BASAL LAMINAE.
In the TUBULES, this basal lamina often FUSES with the basal lamina of the PERITUBULAR CAPILLARIES.

The OUTER MEDULLA contains little more interstitium than is found in the cortex, the INNER MEDULLA contains the largest amount of interstitium that becomes more abundant toward the tips of the medullary papillae. Within the interstitium of the INNER MEDULLA are LIPID-LADEN INTERSTITIAL CELLS that are transversely interposed between the longitudinally running tubules and vessels.

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principle cells in collecting ducts, very few intercalated cells (none shown here)

They are relatively simple and contain few organelles.

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Transitional epithelium is found in the calyces, ureter, and the bladder. It is made of domed cells that are sometimes binucleated.

Hint 31

BLADDER AND URINARY PASSAGES

The calyces, pelvis, ureter, and bladder all have a similar histological structure with the lining mucosa being composed of TRANSITIONAL EPITHELIUM supported by a lamina propria of connective tissue. This epithelial lining becomes gradually thicker as one goes down these passages toward the bladder. Outside the lining mucosa are layers of smooth muscle that are surrounded by an adventitial membrane (except for the upper part of the bladder which is covered by the peritoneal serosa).

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Transitional epithelium is found in the calyces, ureter, and the bladder. It is made of domed cells that are sometimes binucleated.

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Transitional epithelium is found in the calyces, ureter, and the bladder. It is made of domed cells that are sometimes binucleated.

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glomerulus... ball of capillaries. arteriole on each end help regulate flow.

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SEM: Glomerulus. covered by viceral layer of bowmans capsule. very thin layer is parietal layer of bowmans capsule. keeps fluid inside epithelium.

White ARROW: thin layer of parietal epithelium
V= vascular colum

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N= protocytes
M= Major processes
F= filtration slits between pedicles

SEM: zoom in of glomerulus. capillary loop of glomerulus. PODOCYTES

foot processes = pedicles

Interestingly, these foot processes interdigitate with processes from
other podocytes and sit on top of the glomerular basement membrane.
The space between each foot process of the podocytes is called a
filtration slit. Nb: this slit does contain a diaphragm. The slits are
also covered by a sialic acid rich glycocalyc which negatively repels
the adjacent foot processes and keeps the filtration slits open.

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Renal Corpuscle (Mesangial Cells)

Mesangial Cells
Phagocytic cells
Remove foreign material that builds up around the capsular walls and capsular space


(called basal membrane, not basal lamina)

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Renal corpuscle showing vascular pole (a), urinary pole (c ), parietal epithelium (b), visceral epithelium (d), peritubular capillaries (e), and proximal tubules (f). Can you identify a macula densa?


Vascular pole up
Urinary pole down
b= parietal epithelium
d=nucles of a podocyte
e= capillary
f= proximal convoluted tubule
perituble cappilary filled with blood

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PO= podocytes, mesangial cells in between endothelial cells.

RENIN GRANULES in the walls of the afferent arteriole. Formed in the modified smooth muscles that make up all of arteriole

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BS = bowmans space
C= capillary of glomerular

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size shape and charge all affect what gets across this barrier

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OS= outer medulla
IS= inner medulla

Thick Descending Limb
Location: Outer layer of the outer medulla
Defining Characteristic: Cuboidal with microvillus brush border (S3 of PCT)
Thin Descending Limb
Location: inner layer of the outer medulla, and the inner medulla
Defining Characteristic:
Simple squamous epithelium
No microvillus brush border
Thin Ascending Limb
Location: inner medulla
Defining Characteristic:
Simple squamous epithelium
No microvillus brush border
Thick Ascending Limb
Location: Outer Medulla
Defining Characteristic:
Cuboidal with basolateral folds and mitochondria, but NO microvillus brush border

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DIVISIONS OF KIDNEY MEDULLA

Transitions from one segment of the loop of Henle to another occur at specific depths within the substance of the medulla. These regular transitions together with changes in the surrounding vasculature and interstitial tissue result in a division of the medulla into INNER and OUTER ZONES, and the further subdivision of the outer medulla into INNER and OUTER STRIPES. The first transition occurs as the descending thick segment transforms into the descending thin segment. This juncture marks the border between the inner and outer stripes of the outer medulla. The descending thin segment will continue into the inner stripe of the outer medulla and inner medulla to variable depths before abruptly turning and ascending again into the cortical substance of the kidney. The transition from the ascending thin segment to the ascending thick segment marks the juncture between the inner medulla and the inner stripe of the outer medulla. As a result, the inner medulla contains only the ascending and descending thin segments of the loops of Henle, the inner stripe of the outer medulla contains only the ascending thick segments and descending thin segments of the loops of Henle, and the outer stripe of the outer medulla contains only the descending and ascending thick segments of the loops of Henle. It should be noted that the depths to which the loops of Henle descend into the medulla are highly variable and dependent upon the location of their associated renal corpuscles in the cortical substance (see section on “Nephron Heterogenity”). As one descends deeper into the inner medulla there are fewer loops of Henle. Also, the collecting ducts merge with each other to form fewer but larger collecting ducts. Coincident with this reduction in kidney parenchyma is a reduction in the vasculature, but an increase in interstitial tissue. The net result is an overall reduction in tissue and the characteristic tapered appearance of the kidney papillae.

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C= Cortex
M= medulla

Black arrows: Medullary rays made by loops of henle. Rays composed of ascdending and decening loops of henle and collecting ducts

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Glomerulus

S1 portion of proximal convoluted tubules

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Near black arrow= Very thin parietal epithelial

** Same cell/ very thick

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PROXIMAL tubule contains Microvilus Brush Border

MICROVILLUS BRUSH BORDER= ABSORPTION--> lots of mitochondria and basal lateral folds.... broken down to S1, S2, S3

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Microvillus brush border

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S3 Segment- know how to tell this is S3 has elabrate microvillus brush border, but not as many mitochondria or basal lateral folds

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Ascending distal tubule

see microvillus brush border becoming smaller

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Ascending distal tubule

Ascending thin segment = everything below this is in inner medulla

only in outer segment we see thick
inner= thin segments

thick--> thin
squamous--> cuboudal

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What is IM OM or CORTEX

Know the distinguishing features.

proximal convoluted tubles, renal corpuscles and glomeruli= ONLY found in cortex of kidney!!!!

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Md= Macula Densa (part of Jg apparatus)
Arrows= Renin granules (in walls of afferent arteriole)
Aa= afferent arteriole
Ea= efferent arteriole

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CD= collecting duct
DT= distal tubule
Black arrows/ intercalated cells seen near cortex of kidney?)

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Collecting ducts are very easy to identify

unlike other segments, very discrete intercellular borders. Why? NOT ACTIVELY TRANSPORTING anything. Don't need all those borders. very few organelles to stain

NOTE: INNER MEDULLA. these are thin segments from loop of henle (they look the same at light microscopic level

NOTICE: more interstitial/ connective tissue,

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EM showing tall columnar cells making PAPILLARY DUCTS
in papillary region of lobe.

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Black Arrow= Tip of Papilla

creveces= papillary ducts draining uring in to MINOR calynx .... lined with TRANSITIONAL EPITHELIUM (only 2-3 cell layers thick at this point.

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Ureter
notice smooth muscle
peristaltic like wave, not unlike gi

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Once you get to bladder.... much thicker.

surface cells = dome shaped... sometimes binucleated.

THE URINARY SYSTEM/ URETERS/ BLADDER IS THE ONLY PLACE IN THE BODY YOU WILL FIND TRANSITIONAL EPITHELIUM!!!

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What is the functional unit of the kidney? How many does each kidney have?

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The basic structural and functional unit of the kidney is termed the NEPHRON. There are
approximately one million nephrons in each kidney. Each nephron is composed of a spherical structure known as the RENAL CORPUSCLE , and a long URINEFEOROUSuriniferous tubule that is differentiated along its length to perform many different functions. The uriniferous tubules merge with COLLECTING DUCTS that have a different embryological origin than the renal corpuscle and uriniferous tubules.

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In the renal corpuscule, why do we use an EFFERENT arteriole as opposed to exiting via a venule??

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The glomerular capillary tufts arise from afferent arterioles which branch off from interlobular arteries, as the latter course through medullary rays into the cortical substance of the kidney (see renal circulation). Each afferent arteriole divides into capillary bundles that make up the glomerular tuft. Blood exits the
glomerular capillaries by way of an efferent arteriole rather than a venule, thereby permitting smooth
muscle in the walls of the afferent and efferent arterioles to exert control over hydrostatic pressure within the glomerular capillary loops.

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What makes GLOMERULAR CAPILLARIES so unique?!?

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Glomerular capillaries are unique in being lined by a glomerular
endothelium perforated by numerous open fenestrations.

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How much GLOMERULAR FILTRATE do we make every minuet?

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High hydrostatic pressure within the glomerular capillaries forces solute from the blood across the
glomerular wall and into the capsular space of Bowman. The filtrate then passes out of the urinary pole opening and into the uriniferous tubules. Approximately 20% of the blood that enters the kidney ends up as glomerular filtrate. For both kidneys, this amounts to the production of approximately 125 ml of glomerular filtrate every minute. This filtrate has a composition similar to interstitial fluid but contains very little plasma protein.

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Which tubules in the nephron are more sensitive to ischemia?

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Dr. Andrews started the lecture by showing what he believed to be an exciting video of nephrons responding to an ischemic insult. Truthfully, I would rather watch Real Housewives of New Jersey marathon than watch that video again. So you won’t have to, here are the important points from the video: - When you render the kidney ischemic by clapping renal artery you cause kidney cells to swell and eventually burst.
-infuse mannitol (protects kidney form ischemic insult), allowing the tubules remain open
-Counter-balances hypertonicity inside of cells.
- how sensitive tubules are to ischemic insult? The proximal tubules are much more sensitive than the distal tubules.