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for the 2 for the 2 nd nd course course English medium students English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Department of histology, embryology, cytology Volgograd Volgograd , 2015 , 2015

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Page 1: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

for the 2for the 2ndnd course courseEnglish medium studentsEnglish medium students

for the 2for the 2ndnd course courseEnglish medium studentsEnglish medium students

VOLGOGRAD STATE MEDICAL UNIVERSITYVOLGOGRAD STATE MEDICAL UNIVERSITY

Department of histology, embryology, cytologyDepartment of histology, embryology, cytology

VolgogradVolgograd, 2015, 2015

Page 2: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Objectives:

1. To appraise the kidneys as exquisite filters, designed to eliminate from the blood largely nitrogenous wastes, excess electrolytes, and water.

2. Document the role of the kidney in the preservation of homeostasis in the body

3. Extrapolate from its unique vasculature, how kidney is able to concentrate the urine 100-fold.

4. Conceptualize in a sketch the nephron as the functional and anatomical unit of the kidney.

5. Evaluate the function and structure of the ureter, urinary bladder and urethra.

6. Assess the kidneys as endocrine organs and how they are affected by certain hormones produced elsewhere in the body.

Page 3: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The components of the urinary system are the kidneys, ureters, urinary bladder and urethra.

General Provisions:

The urinary system functions in the formation of urine, regulation of blood pressure and fluid volume of the body, acid-base balance, and formation and release of certain hormones.

Page 4: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

ExcretoryHomeostaticEndocrine

Secretion ofrenin (increasesblood pressure)

Served by 1 000 000 nephrons

Eliminate nitrogenousblood impurities,electrolytes and water

Preserves homeostasis through:1) ultrafiltration

of plasma

2) selective resorptionof filtrate

Essential to life

FUNCTIONS OF THE KIDNEY

Page 5: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Adult Human KidneyEach kidney has two distinct

zones: an outer cortex and inner medulla. The cortex forms an outer shell and also forms columns (of Bertin) which lie between the individual units of the medulla.

The medulla is composed of a series of conical structures (medullary pyramids), the base of each cone being continuous with the inner limit of the cortex and the pointed peak of the pyramid protruding into part of the urine collecting system (calyceal system) towards the hilum of the kidney. This pointed tip is known as papilla. Each human kidney bears 10-18 medullary pyramids thus 10-18 papillae protrude into the collecting calyces.

Each medullary pyramid, with its associated shell of cortex, comprises a functional and structural lobe of kidney. The lobar architec-ture is less obvious as kidney increases in size with increasing age.

Page 6: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

In fetal kidney this lobar architecture is clearly visible. Within the kidney in the hilum where the ureter in cross section and vessels entering and leaving the kidney are seen.

The cortex is located peripherally, the cortical columns dip between the medullary pyramids, with the base of the pyramid resting against the peripheral cortex and the apex toward the hilum.

Between the pyramids are the interlobar vessels: the artery is a branch of the renal artery, the veins form the renal vein in the marginal zone, between the cortex and base of the pyramids. The arcuate arteries and veins are tributaries of the interlobar vessels.

Kidney and Adrenal, Fetal,

Rhesus monkey,H. & E., x 6.

Page 7: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The cortical region is subdivided into cortical labirynth with renal corpuscles (RC), convoluted renal tubules (T), blood vessels (V), and the medullary rays (MR).

NB! The medullary rays though structurally similar to medulla, are considered part of cortex. They are finely striated extensions of base of a pyramid reaching into cortex and almost to renal capsule and representing an axis of the renal lobe.

In the medulla are many tubules of the loops of Henle and collecting ducts (CD), sectioned in different planes. Islands of medullary capillaries, the vasa recta (VR) are shown.

Renal Cortex and Medulla

Page 8: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Renal lobe – is a part of the kidney parenchyma comprises of a pyramid and overlying renal cortex.

Renal lobule – is a small portion of the renal cortex composed of a medullary ray with its immediately associated cortical tissue.

DEFINITIONS:

Cortex

Medulla

Lobule

Lo

be

Pyramid

Medullary ray

Page 9: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The medullary rays contain the straight portions of proximal and distal tubules (medullary segments), the thick segments of ascending arms of Henle's* loops, and the straight collecting tubules.

The cortex is composed of radiating medullary rays, alternating with regions containing glomeruli and convoluted renal tubules (cortical labyrinth). Other names for these two divisions are pars radiata for the medullary rays, and the pars convoluta for the cortical labyrinth. The cortical labyrinths contain glomeruli, proximal and distal convoluted tubules, and the arched collecting tubules.

Kidney, CortexH & E, x50.

Henle was a nineteenth-century German anatomist.

Page 10: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The major gas exchange takes place in the secondary capillary system.

GENERAL PROVISIONS REGARDING ORGAN BLOOD SUPPLY

In every organ the capillary network lies between the terminal part of the arteriolar and proximal part of the venular system and it is the major site of O2/CO2 exchange.

In contrast renal vascular system has a highly speciailized preliminary capillary network – the glomerular tuft (glomerulus).

Glomerulus is the site of filtration of the waste products from plasma.

Glomerulus does not transfer oxygen to the tissues, nor does it take up significant amount of carbon dioxide.

Page 11: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

To understand the histophysiology of kidney its vascular supply should be appreciated.

In general the renal venous drainage mirrors the arterial supply (except afferent -efferent arterioles).

Each kidney is sup-plied by a renal artery, a direct branch of the abdominal aorta. It sub-divides into the dorsal and ventral branches as it enters the hilum of the kidney which give off interlobar arteries situated between the pyramids. At the level of the pyramid bases interlobar arteries divide into arcuate arteries.

Blood Supply of the Kidney

Page 12: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Blood Supply of Kidney

Interlobular arteries derived from the arcuate arteries enter cortical labyrinth to reach the renal capsule supplying a stellate subcapsular arteriolar and capillary plexus. Finally they form superficial cortical veins which unite to form stellate veins draining into interlobular veins.

Some interlobular arteries perforate capsule and, as capsular arteries vascularize capsule. There are anastomoses between capsular arteries and interlobular veins. Understanding of the renal vasculature is essential for comprehension of filtration in the renal corpuscle.

Page 13: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

From the arcuate arteries interlobular arteries emerge radially and at fairly regular intervals. From them, at right angles, arise afferent arterioles which break up into capillaries of the renal glomerulus.

Glomerular capillaries unite to form efferent arterioles which (if associated with the cortical nephrons) break up into a peritubular capillary network which drains both into interlobular veins and radially oriented deep cortical veins emptying into arcuate veins, tributaries of the interlobar veins from where blood enters renal vein and finally inferior vena cava.

Blood Supply of the Kidney

Page 14: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The described course is true for the cortical nephrons making up about 80% of all nephrons and with renal corpuscles located in the peripheral region of the cortex.

The remaining 20% of the nephrons are juxtamedullar with the renal corpuscles located in the cortex adjacent to the medulla. Their blood supply bears special features.

The Two Type of the Nephrons.

Page 15: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The efferent arterioles of the medul-lary nephrons pass into the medulla as descending thin-walled nonbranched arteriolae rectae spuriae – a part of the vasa recta. These form a hairpin loop, turning upward toward cortex to empty as venous vasa recta into interlobular veins.

Compare peritubular plexus of the cortical nephrons and vasa rectae of the juxtamedullary nephrons.

Blood Supply of Cortical and Medullary Nephrons

Page 16: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Interlobular arteries derived from the arcuate arteries enter cortical labyrinth to reach the renal capsule supplying a stellate subcapsular arteriolar and capillary plexus. Finally they form superficial cortical veins which unite to form stellate veins draining into interlobular veins.

Some interlobular arteries perforate capsule and, as capsular arteries, vascularize capsule. There are anastomoses between capsular arteries and interlobular veins. Understanding of the renal vasculature is essential for comprehension of filtration in the renal corpuscle.

Blood Supply of Kidney

Page 17: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Renal corpuscles (RC) are scattered in the renal cortex surrounded by tightly packed renal tubules, mostly proximal convoluted tubules (PCT) and fewer distal convoluted tubules (DCT) which usually have a wider lumen, but are smaller in the overall diameter. Part of a medullary ray (MR) is visible and contains straight segments of proximal and distal renal tubules, and collecting ducts. All of these components are supported by the interstitial tissue.

Renal Cortex

Page 18: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Renal Corpuscle Collectively glomerulus and the Bowman’s capsule surrounding it are referred to as the renal corpuscle. It is roughly spherical and measures 150 to 250 mcm.It is entered by the afferent arteriole and drained by the efferent arteriole.

The capsule is the a dilated blind-ending proximal part of the renal (uriniferous) tubule, it contains parietal (outer) in visceral (inner) layers. The modified cells of the inner layer are known as podocytes.

Page 19: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Long thin artery leading to glomerulus (look in lower mid-picture). Note long, thin endothelial nuclei lining the lumen. Circular muscle fibers have been cross-cut and look almost like a simple cuboidal epithelium outside the endothelium.)

Kidney

Page 20: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The capillary loops are seen supported by the podocytes on one side and by mesangial cells in the regions where the podocytes may not come into contact with a capillary. This is a pericyte-like intraglomerular mesangial cell which is phagocytic, with a function of resorbtion of the basal lamina, it may be contractile as it has receptors for vasoconstrictors (angiotensin- II) thus reducing blood flow through glomerulus. It may be responsible for many pathological processes in the kidney.

Another type of the mesangial cells – the extraglomerular one – may be seen at the vascular pole of the corpuscle.

Renal Corpuscle

Page 21: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Renal corpuscle displays polarity. Afferent arteriole (AA) enters vascular pole of a renal corpuscle, and branches forming capillaries of the glomerulus (G). Bowman’s or urinary space (S), separates glomerulus from the parietal layer of Bowmen’s capsule (arrow).

Renal Corpuscle

Page 22: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Continuity of the renal corpuscle (RC) with proximal convoluted tubule (PCT) marks the urinary pole. The cuboidal epithelium of the tubule changes to squamous epithelium (arrows) of Bowman’s capsule.

Renal Corpuscles

Page 23: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

FILTER BARRIER

The capillaries constituting the glomerulus are similar to the fenestrated type of capillaries. Their endothelial cells are highly attenuated, except for the region containing nuclei, but the pores are usually not covered by a diaphragm. The pores are large, ranging between 70 and 90 nm in diameter; hence these capillaries act as a barrier only to formed elements of the blood and to macromolecules whose effective diameter exceeds the size of the fenestrae (albumin – 69,000 dalton).

Page 24: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Investing the glomerulus is a basal lamina 300 nm thick, consisting of the 3 layers. The middle dense layer, the lamina densa, is about 100 nm in thickness and consists of collagen of the IV type. Less electron-dense layers, the laminae rarae, which contain laminin, fibronectin, and a polyanionic proteoglycan rich in heparan sulfate, are located on the either side of the lamina densa.

Some refer to a lamina rara interna and lamina rara externa accordingly. Fibronectin and laminin assist the pedicels and endo-thelial cells to maintain their at-tachment to the lamina densa.

FILTER BARRIER

Page 25: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Endothelium

The visceral layer of the Bowman’s capsule is composed of epithelial cells that are highly modified to perform a filtering function. These large cells called podocytes, bear numerous long, tentacle-like cytoplasmic extensions, primary (major) processes, which follow but usually do not come in close contact with the longitudinal axes of the glomerular capillaries. Each primary process bears many secondary processes, also known as pedicles, arranged in an orderly fashion. Pedicles completely envelope most of the glomerular capillaries by interdigitating with pedicles from neighboring major processes of different podocytes.

Page 26: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

EM of triangular shaped podocyte with its many terminal end feet (foot processes) touching the basement membrane (dark) which is shared on its other surface by endothelium of a capillary.

RENAL FILTER BARRIER, TEM, x 50,000

Page 27: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Interdigitation between podocytes occurs in such a fashion that narrow cleft, 20 to 40 nm in width, known as filtration slits remain between adjacent pedicles. Filtration slits are not completely open; instead, they are bridged by a thin (6 nm thick) slit diaphragm, which extends between neighboring pedicels and acts as a part of a filtration barrier.

Filter Barrier, TEM

Page 28: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Detail of end feet of podocyte on the basement membrane. The basement membrane (basal lamina) is continuous, but the fenestrated capillary endothelium has pores. Glomerular filtrate passes from the capillary lumen, through the layers seen here, into the lumen of Bowman's capsule. Between the foot processes are thin slit membranes.

Filter Barrier, TEM

Page 29: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

1. Filtration slits between adjoining pedicels bridged by thin diaphragms,

in association with

2. capillary endothelium and

3. the basal laminae of the capillary endothelium and podocyte,

contribute to the formation of the filtration barrier.

FILTRATION BARRIER:

Page 30: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

becuse the BL traps larger macromolecules, it would become clogged were it not continuously phagocytosed by intraglomerular mesangial cells and replenished by both the visceral layer of Bowman’s capsule (podocytes) and glomerular endothelial cells.

Filtration Process:

fluid leaving the glomerular capillaries through the fenestrae is filtered by the basal lamina. The lamina densa traps larger molecules (>69,000 Da), whereas the polyanions of the laminae rarae impede the passage of negatively charged molecules and molecules that are incapable of deformation. The fluid that penetrates the lamina densa, passing through the pores in the diaphragm of the filtration slits and entering Bowman’s space, is called the glomerular ultrafiltrate,

Page 31: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

BASEMENT MEMBRANE ABNORMALITIES IN GLOMERULAR DISEASE

Abnormalities in the structure of the glomerular BM are responsible for some important kidney diseases which are characterized by an excessive loss of protein in urine (proteinuria). Sometimes so much is lost in the urine that the capacity of the liver to synthesize fresh protein (particularly albumin) is outstripped. The patient then develops a low blood albumin (hypoalbuminemia), and edema due the low oncotic pressure of the blood.

The combination of proteinuria, hypoalbumonemia and edema is called nephrotic syndrome.

There are many causes of the nephrotic syndrome, but all appear to be related to a structural or functional abnormality of the glomerular BM.

Diseases in which the abnormality is structural include diabetes mellitus and membranous nephropathy.

Page 32: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

EM of the filter barrier. A uniformly thickened basement membrane from a patient with diabetes mellitus who presented with the nephrotic syndrome.

In nephrotic syndro-me associated with diabetes mellitus the glomerular basement is thickened 3-5 fold and the demarcation into the three lami-nae is lost.23

Page 33: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

PODOCYTE ABNORMALITIES IN GLOMERULAR DISEASE

The podocyte abnormalities are associated with the polyanionic charge which possibly explains the protein leak.

In children, the most common cause of the nephrotic syndrome is the so-called minimal change nephropathy.

By light microscope the glomerulus appears normal but EM reveals loss of the foot process pattern, with the outer surface of the glomerular capillaries being covered by an almost continuous sheet of podocyte cytoplasm, probably representing process remnants.

The abnormality is usually only temporary, structure and function return to normal in time.

Page 34: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The functional unit of the kidney is the uriniferous tubule, consisting of the nephron and the collecting tubule, each of which derived from a different embryologic primodiums.

There are two types of the nephrons: the cortical and juxtamedullary neurons, classified by their location in the kidney cortex and differing in their structure and blood supply.

The nephron begins as a distended, blindly ending invaginated tubule, known as Bowman’s capsule. Glomerulus is not a part of the nephron.

Uriniferous Tubules.

Page 35: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

The region of continuation between the renal corpuscle and the uriniferous tubule which drains the Bowman’;s space is called the urinary pole. The ultrafiltrate enters the urinary space and leaves the corpuscle at its urinary pole through the pro-ximal convoluted tubule.

Renal Corpusle

Page 36: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

constitute much of the renal cortex. Each of them is about 60 mcm in diameter and approximately 14 mm long. It consists of a highly tortuous region – the pars convoluta (proximal convoluted tubule) located near the renal corpuscle, and a straighter portion, the pars recta (descending thick limb of the Henle’s loop).

Proximal Tubules:

Page 37: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

PROXIMAL CONVOLUTED TUBULE

Brush border of microvilli enables the tubules to reabsorb about 70% of the glomerular filtrate. The membrane contains Na+, H+, and Cl- antiport exchangers and enzymes that digest small amino acids.

Deep baso-lateral enfoldings or invaginations greatly increase surface area to provide effective reabsorbtion of fluid and solutes that pass along it.

Page 38: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Kidney, Cortex, x 612.

Proximal tubule: Lumen continuous with that of glomerular capsule (Bowman's space). Large cuboidal cells, abundant eosinophilic cytoplasm, and large round nuclei. Brush border. Neck: The first part of the proximal tubule leading away from the glomerulus. Narrow and straight.

The ultrafiltrate from the glomerulus enters the urinary space and is drained from there by the neck of the proximal tubule. The simple cuboidal epithelium of the proximal tubule adjoins the simple squamous epithelium of the parietal layer of the Bowman’s capsule.

Page 39: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Detail of renal corpuscle. Dark pink epithelium = proximal tubule. Lighter pink (as at upper top left) = distal tubule. Renal corpuscle with connection to proximal tubule at lower border.

Kidney, Hematoxylin-Eosin.

Page 40: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Dark pink = proximal tubule. Lighter, low cuboidal epithelium (as at top left) = distal tubule.

Kidney, Hematoxylin-Eosin.

Page 41: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Proximal and distal convoluted tubules (EM). Proximal convoluted tubules contain microvilli, intercellular junctions, mitochondria for energy supply and infolded BM. Distal has no brush border. Peritubular capillaries lie in the connective issue between tubules.

NEPHRON, TEM

Page 42: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Higher EM of proximal tubule with its brush border (arrow), which indicates absorption by the cell.

NEPHRON, TEM

Page 43: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

EM of base of epithelium of proximal convoluted tubule. Note basement (basal) lamina and the great infolding of the cell membrane. The many folds also provide increased cell surface for passage of absorbed fluid and ions into the peritubular capillary below. The folds contain Na+K+ adenosine triphosphate complexes that pump Na+ out of the cell, coupled to transport of glucose and amino acids. Sodium is followed by chloride to maintain electrical nuetrality and by water to maintain osmotic equilibrium.

NEPHRON, TEM

Page 44: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Cytoplasm of the epithelial cells is eosinophylic granular cytoplasm. The folds of the BM, plus the many mitochondria lying in them, tend to give the cytoplasm a striated look in light microscopy. The cells have elaborated an intricate system of interlocking and interwoven lateral cell processes. Thus, the lateral cell membranes are unusually indistinguishable with the light microscope.

Proximal Convoluted Tubuleof the Nephron

Page 45: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

PAS-staining of the proximal convoluted tubule showing carbo-hydrate-rich basal laminae and microvilli. The brush border enhances reabsorbtion of fluid and solutes from the lumen through or between the cuboidal epithelial cells and into capillaries. These tubules also secrete organic bases and H+ into the lumen.

Proximal Convoluted Tubules, Periodic Acid-Shiff Base Stain

Page 46: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Pars recta of the proximal tubule descends in medullary rays within the cortex and then in the medulla to become connected with a loop of Henle at the junction of the outer and inner stripes.

Cells of the pars recta of the proximal tubule are low cuboidal. On the contrary to the cells the distal part of the proximal tubule convoluted tubule, they do not form apical canaliculi for the protein resorption, contain fewer mitochondria and less elaborate intercellular processes.

PARS RECTA OF THE PROXIMAL TUBULE

Page 47: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Upon entering the medulla, the proximal tubule shows an abrupt transition into the descending thin limb of Henle’s loop in which the lining epithelial cells are flat with nuclei that protrude into the lumen. This appearance persists in those loops, which turn back to form thin, ascending limbs.

Depending on whether a nephron has a short or long loop of Henle, the thin limbs are 1-10 mm in length.

LOOP OF HENLE

Page 48: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Thin segment of Loop of Henle (in the middle), with a simple squamous lining.

Kidney, Medulla.

Page 49: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Cross cuts in medulla. Two pale collecting tubules in the middle. Simple squamous lining indicates thin loops of Henle. Compare these with blood vessels, which contain r.b.c.'s. (Look for vessels up near top center and to right; also in lower left quadrant of field.) Notice the blue c.t. stroma in between the tubules.

Kidney. Medulla.

Page 50: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Large pale tubules are collecting tubules, with clear epithelial cell boundaries. Brighter pink tubules are thick portions of loops of Henle; these are basically like distal convoluted tubules in their histology, so would be ascending limbs.

Kidney. Hematoxylin-Eosin.

Page 51: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Distal tubule is composed of the three histologically distinct segments: thick ascending Limb of Henle’s loop; macula den-sa and distal con-voluted tubule the latter being the last part of the nephron.

Distal Tubule

Page 52: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

DISTAL TUBULEThe transition from thin to thick ascending limb is recognized by the appearance in the latter segment of low cuboidal cells, at the US-level, by abundant mitochondria and invaginations of the basolateral membrane. These feature are associated with active transport mechanisms in which salt is reabsorbed into the interstitium, to produce a dilute tubule fluid and hypertonic interstitium. The ascending thick limb extends upward toward cortex and returns to the parent renal corpuscle. At the contact point with the extraglomerular mesangial region, the cells are narrow and clustered side-by side to form the macula densa.

Page 53: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Macula densa is a type of chemoreceptor that monitors luminal Cl- concentration and is involved with adjustment of the glomerular filtration rate. Together with the modified smooth muscle cells of the afferent arteriole (juxtaglomerular cells containing specific granules of renin) and extraglomerular mesangial cells they constitute juxtaglomerular apparatus of kidney.

ENDOCRINE APPARATUS of the KIDNEY

Page 54: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

ENDOCRINE APPARATUS OF THE KIDNEY

Page 55: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Juxtaglomerular cells: Granular variety of myoepithelioid cells in the wall of the afferent arteriole. Replace the typical smooth muscle cells of the tunica media of the artery.

KIDNEYJuxta-

glomerular cells,

Mallory Stain, x1614

Afferent arteriole: Terminal branch of the interlobular artery entering the glomerulus. The renal afferent arterioles are volume receptors and are sensitive to changes in perfusion (blood) pressure.

Page 56: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015
Page 57: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Angiotensin II influences the adrenal cortex to release aldosterone increasing reabsorbtion of sodium and calcium.

FUNCTIONAL CORRELATES:

When cells of the macula densa detect a low sodium concentration in the ultrafiltrate, they cause juxtaglomerular cells to release the enzyme renin, which converts angiotensin to angiotensin I a mild vasoconstrictor.

Angiotensin I is converted to angiotensin II by angiotensin-converting enzyme (ACE) which is a potent vasoconstrictor.

Page 58: For the 2 nd course English medium students VOLGOGRAD STATE MEDICAL UNIVERSITY Department of histology, embryology, cytology Volgograd, 2015

Distal tubule: Cuboidal cells without a brush border, which stain less intensely than the proximal tubule cells. It is about one third the length of the proximal tubule. The distal tubule is continuous with the collecting tubules.

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Distal Convoluted Tubule

The tubules have no brush border, but their numerous mitochondria (arrows) provide the adenosine triphosphate necessary for active transport of NaCl reabsorbed from luminal fliud, which amounts to 5-10% of the filtered load of NaCl. This nephron segment, although relatively impermeable to water, is not homogeneous in either morphology or function and is a transitional tubule that leads to connecting segment or tubule.

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Medullary rays (MR) extend down from the cortex into the medulla and contain straight parts of proximal and distal tubules and collecting ducts (CD) with wide lumens. The arteries (A) and veins (V) are related to arcuate vessels that arise at the corticomedullary junction. Medullary rays are prominent because they provide the route by which the descending and ascending limbs of the loop Henle reach the inner medulla. Juxtamedullary nephrons have the longest loops, but in the human kidney most cortical nephrons have relatively short loops.

Cortico-Medullary Region

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Distal convoluted tubule: Wider lumen, shorter cells, without brush border. The ratio of cross-sectins of proximal to distal convoluted tubules surrounding any renal corpuscle is 7:1

KIDNEY

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Collecting tubules represent transitio-nal segments betwe-en distal convoluted tubules and long collecting ducts that extend to the papillary region of the renal pyramid. Cortical collecting tubules show a cuboidal cell lining which becomes taller, to form columnar cells, as the ducts descend through the medulla.

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Nephrons emptying into a collecting tubule. Notice that the closer to the medulla a glomerulus lies, the longer the loop of Henle is. Also notice that the inner zone of the medulla (lowest section of the picture) contains only thin limbs of the loop of Henle, plus collecting ducts. This is the area where the counter-current mechanism for urine concentration (carried out between the tubules and the surrounding peritubular capillaries) is most active. To make his drawing clear, the artist has made one accommodation that is not quite accurate histologically; namely, within the cortex, the straight positions of the nephrons (that is, the thick and thin portions of the loops of Henle) should lie immediately next to the collecting duct, thus making up the medullary ray. The glomeruli and convoluted portions of the nephrons would then lie on either side of the ray. The ray is the central axis of a lobule. NEPHRON

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Medullary Ray, transverse section

Collecting ducts (CD) with distinct cell outlines, straight portions (pars recta) of the proximal tubules with brush border (PCD) and thick ascending limbs (TAL) of the loop of Henle. The TAL extrudes Na+ into the interstitium, but it is impermeable to water so the osmolarity of the tubular fluid decreases as it approaches the cortex and the distal tubule.

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Collecting Duct

A longitudinal section of collecting duct (CD) showing orderly cuboidal epithelium and prominent plasma membrane borders between cells. These ducts absorb water and urea and partly determine urine volume and concentration. Permerability is regulated by antidiuretic hormone, and also aldosterone.

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Many collecting tubules with wide lumen are present in the inner medulla. In the interstitium are medullary interstitial cells that support a rich vascular plexus of capillary loops and the thin limbs of the loop of Henle.

Collecting ducts are permeable to water in the presence of antidiuretic hormone, which also increases urea permeability; the urea is recycled in the nephron, and contributes to the high osmolarity of the inner medulla.

Collecting Tubules of the Medulla

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There is close relationship between collecting ducts (CD), thick ascending limb (TAL), and thin limb (tL) of the loop of Henle and the peritubular capillaries or vasa recta (VR). Water moves from thin limbs to interstitium (I) in response to high osmolarity of the interstitial region created by Na+ movement from the TAL, the cells of which contain many mitochondria to energize the active transport of Na+ through the base of the tubule. Collecting ducts reabsorb water from lumen to interstitium in response to antidiuretic hormone.

Medulla of the Kidney

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Vasa Recta

Vasa recta are columns of capillaries that are prominent in the medulla. They are a mixture of descending vessels that originate from glomerular efferent arterioles, which extend into the inner medulla and return as venous or ascending vessels, that drain into corticomedullary veins. In the outer medulla, the vasa recta form vascular bundles mainly surrounded by thick and thin limbs of Henle’s loop.

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region of uriniferous tubule

structure major functions miscellaneous comments

renal corpuscle

simple squamous epithelium, fused basal laminae, podocytes

filtration filtration barrier: endothelial cell, fused basal laminae, filtration slits

proximal tubule

simple cuboidal epithelium with brush border and vbasolateral striations

resorption of 67-80% of water, sodium, and chloride (reducing volume of ultrafiltrate), resorption of 100% of protein, amino acids, glucose & bicarbonate

sodium pump in basolateral membrane; ultrafiltrate is isotonic with blood

descending thin limb of Henle’s loop

simple squamous epithelium

completely permeable to water & salts (reducing volume of ultrafiltrate)

ultrafiltrate is hypertonic with respect to blood, urea enters lumen of tubule

ascending thin limb of Henle’s loop

simple squamous epithelium

impermeable to water, permeable to salts; sodium & chloride leave tubule to enter renal interstitium

ultrafiltrate is hypertonic with respect to blood; urea leaves renal interstitium and enters the lumen of tubule

Structure & Function of the Uriniferous Tubule

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Region of uriniferous tubule

Structure Major functions Miscellaneous comments

ascending thick limb of Henle’s loop

simple cuboidal epithelium

impermeable to water; chloride & sodium leave tubule to enter renal interstitium

ultrafiltrate becomes hypotonic with respect to blood; chloride pump in basolateral cell membrane is responsible for the establishment of osmotic gradient in interstitium of outer medulla

macula densa

simple columnar epithelium

monitors sodium level & volume of ultrafiltrate in lumen of distal tubule

contacts & communicates with juxtaglomerular cells

distal convolted tubule

simple cuboidal epithelium

responds to aldosterone by resorbing sodium & chloride from lumen

ultrafiltrate becomes more hypotonic (in presence of aldosterone); sodium pump in basolateral membrane; potassium is secreted into lumen

collecting tubule

simple cuboidal epithelium

in the presence of ADH, water and urea leave the lumen to enter the renal interstitium

urine becomes hypertonic in the presence of ADH; urea in interstitium is responsible for gradient of concentration in interstitium of the inner medulla

Structure & Function of the Uriniferous Tubule

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The vasa recta have a slow blood flow and operate a countercurrent exchange mechanism of water and solutes between their plasma and the interstitial fluid. These capillaries supply nutrients and remove wastes from the interstitium, but they do not wash away the solutes within the medulla necessary to maintain the gradient of salinity. Descending or arterial capillaries (A) are smaller with thicker walls compared to ascending or venous capillaries (V).

The Vasa Recta

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Apex of a Renal Pyramid

Collecting ducts terminate, with prior fusions (F), at a papilla to form wide ducts of Bellini which open, sieve-like (arrows), at the area cribrosa. The cavity of the minor calyx (MC) is lined by transi-tional epithelium, & conveys urine from papilla to the renal pelvis.

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KIDNEY, Papilla, area cribrosa, minor calyx , x162

Papillary ducts (of Bellini). Arise by convergence of collecting tubules in the medulla near the pelvis. Have large lumina lined by tall columnar cells and open at the area cribrosa at the apex of the papilla. Cytoplasm of epithelial cells is clear; nuclei are dark and basally located. The tops of cells tend to bulge into the lumen. Minor calyx: Subdivision of a major calyx in the pelvis of the kidney, minor calyx is an infolded tube forming a double-walled cup. The inner wall of the calyx fits over the papilla of a pyramid. The transitional epithelium of the minor calyx is continuous with the columnar epithelium of the papillary ducts.

Area cribrosa: The sieve-like appearance of the papilla is produced by a large number of collecting tubules passing through it.

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Renin also affects blood volume and osmolarity by initiating a chain of events leading to the release of the hormone aldosterone by the cells of the zona glomerulosa of the adrenal cortex. Aldosterone acts upon the renal tubules to enhance sodium reabsorption.

CLINICAL CORRELATIONS

A decrease in afferent arterial volume secondary to low perfusion pressure results in the release of renin.

Renin is an enzyme that is released into the blood and acts upon blood proteins to produce a potent vasoconstrictor, angiotensin, which can, under abnormal conditions, elevate blood pressure to dangerous levels.

Hypertension of renal origin in humans can be cured by removal of the diseased or ischemic kidney.

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The ureter is lined with with typical transitional epithelium (T), fibroelastic lamina propria (LP), and circula muscularis externa (ME). Urine passes along urtere in peristaltic waves when the lumen changes from stellate to ovoid.

Proximal Ureter, the transverse section

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Distal Ureter, the transverse section

Distal ureter has a thick smooth muscle coat (M, sometimes seen in three layers) and thin lamina propria. Through autonomic nerve supply, the muscle ensures that peristaltic forces deliver urine from the ureter into the bladder.

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Key Features of the Urinary System

Kidney Primary LocationFeatures of Epithelium

Other Features

Proximal convoluted tubule

Cortex Large granular, dark-staining cells; brush border; not all cells show a nuclear profile

Stellate or irregular lumen

Distal convoluted tubule

Cortex Light-staining columnar cells; each cell shows nuclear profile

Smooth luminal surface, large, circular in outline

Renal corpuscle poles (Bowman’s capsule, glomerulus

Cortex Glomerular epithelium – light-staining nuclei

Vascular and urinary thick basal lamina

Thin segment (loop of Henle)

Medulla Light-staining tubule lined by simple squamous epithelium

Narrow lumen

Thick segment (loop of Henle)

Medulla Light-staining cuboidal cells

Wider lumen

Collecting tubule Medulla Light-staining columnar cells, distinct

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Extrarenal Passages Epithelium Supporting Wall

Ureter (proximal two-thirds)

Transitional (4-5 cell layers)

Inner longitudinal and outer circular smooth muscle

Ureter (distal one-third)

Transitional (4-5 cell layers)

Inner longitudinal and outer circular smooth muscle

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Bladder.

A low magnification showing non-distended, folded mucosa (M) and small strands of smooth muscle (S) in the lamina propria (LP), which is a normal finding but is not described as a muscularis mucosae. The external smooth muscle, showing three interwoven divisions (1,2,3), functions to allow bladder filling and contraction during micturition reflex.

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Transitional epithelium of the bladder is impermeable to urine and for this depends upon a thick plasma membrane that faces the lumen, together with intercellular tight junctions. The dome-shaped appearance of the superficial cells is typical of relaxed bladder mucosa, which is usually 4-5 cell layers in deapth and contains cuboidal and columnar cells.

Bladder.

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Transitional epithelium -- diagnostic for urinary tract. The surface cells are characteristically dome-shaped and puffy.

Transitional epithelium from a distended urinary bladder (right); compare with the contracted wall (left). When stretched, the epithelium becomes very thin, with fewer layers of cells, and the surface cells tend to be flattened. There's only the one layer of flatter cells, however, which is quite different from the appearance of stratified squamous epithelium (with which this might be confused.)