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THE KIDNEY

CHIEF FUNCTIONS

1. Elimination of nitrogenous wastes, e.g., urea and uric acid.

2. Osmoregulation - maintaining the balance between water and electrolytes in the body' s fluid compartments.

3. Regulation of blood pressure through cells of the juxtaglomerular apparatus.

4. Regulation of the production of erythrocytes through the release of erythropoietin.

General Anatomy:

The kidneys are two bean-shaped organs embedded retroperitoneally ( behind the peritoneum ) in the lower back. The organ is covered by a tough, outer capsule. Internally, the kidney is divided into an outer cortex and inner medullary tissue ( medulla ). Pyramidal structures (renal pyramids) are located  in the medullary region. Urine production begins in the cortex. It flows steadily through the medullary pyramids to the minor and major calyxes. Finally, the urine collects in the renal pelvis.   From here it moves down the ureter to the urinary bladder. Noose-like sphincters retain urine in the bladder. Relaxation of the sphincters and contraction of the smooth muscle in the wall of the bladder expel the urine out of the body through the urethra.

OSMOREGULATION BY THE KIDNEY

The regulation of the fluid - electrolyte balance in the body is due to three activities of the kidney;  glomerular filtration. tubular secretion and tubular reabsorption. These three activities are carried out by the nephron. The nephron consists of a glomerulus and a long tubule which shows clearly defined regions. Each glomerulus consists of a cluster of capillaries which fill the invaginated, hollow, blind end of a tubule. The thinned out walls of this tubule end form the inner and outer walls of Bowman's capsule. The filtrate moves from the glomerular capillaries into the cavity of Bowman's capsule, From here it moves through the contorted proximal convoluted tubule. The filtrate then moves down into the medullary region and back to the cortical area through the loop of Henle, Leaving the ascending limb of the loop, the filtrate (urine) passes through the distal convoluted tubule and enters the collecting duct. Several other distal tubules empty their urine into this collecting duct,

GLOMERULAR FILTRATION

     The movement of fluid from the blood into the capsular space of Bowman's capsule depends upon the interaction of a number of forces:

1. Glomerular blood hydrostatic pressure (GBHP) -  This is the chief force. It is the pressure of blood in the glomerular capillaries, i.e., 75mm.

2. Capsular hydrostatic pressure (CHP) - CHP is a back pressure due to the presence of fluid already in the renal tubule and the resistance of the tubule walls.

3. Blood Colloid osmotic pressure (BCOP) - The presence of non-filtrating proteins in the blood of the glomerular capillaries creates an osmotic pull on water in the relatively protein-free filtrate.

Pressure #1 is opposed by Pressures #2 and #3, This produces an effective filtration pressure (Peff) of 25mm Hg.

     Pef f   =   GBHP  -  ( CHP + BCOP)

Peff = 75mm Hg - (20mm Mg + 30mm Hg)

                  Peff = 25mm Hg

     25mm Hg is the pressure producing the filtrate within each glomerulus or about 125ml of filtrate/min  for all nephrons of both kidneys (Glomerular filtration rate).

TUBULAR REABSORPTION

Most of the materials filtered out of the glomerular capillaries is returned to the blood through the walls of the peritubular capillaries and vase recta. For example, water, glucose, amino acids, Na+, K+, Ca++, C1-, HCO3-, and HPO4.   Certain nitrogenous wastes are only slightly reabsorbed or not at all, e.g., urea, uric acid, creatinine.   Sodium ions are actively reabsorbed into the blood at the PCT, DCT and the collecting ducts. The control of this reabsorption is achieved through the renin-angiotensin pathway.

Water - About 80% of he water reabsorbed by the blood from the glomerular filtrate accurs at the PCT. The transport of Na into the peritubular capillaries there creates a high osmotic pull in the blood of these vessels. Water moves from the tubule into the blood to balance this osmotic imbalance. Since this movement of water is due solely to the law of osmosis and is not subject to direct regulation, it is referred to as obligatory reabsorption. Anti-Diuretic Hormone regulates the transport of the remaining filtrate water. This reabsorption may occur to a small or great degree. It may also not occur at all.  Thus, it is called facultative reabsorption.

Glucose - is reabsorbed actively across the membranes of the PCT using a carrier method. Since this mechanism utilizes a finite number of carrier molecules, the ability of the system to remove all of the glucose from the filtrate will depend upon the level of glucose in the blood.  Normally, all of the glucose in the filtrate is returned to the blood.  In a diabetic, the level of glucose is so high that the number of carrier molecules becomes inadequate and glucose remains in the urine.

TUBULAR SECRETION

     In the DCT, a number of substances are secreted into the filtrate from the blood by the cells of this portion of the tubule, e.g.,H+,  NH3,   K+, creatinine and certain drugs (amphicillin). The secretion of H+ , and NH3   assists in the maintainence of blood pH by conserving NaHCO3 and eliminating H+.

AMOUNTS OF DIFFERENTS SUBSTANCES FILTERED AND REABSORBED BY THE KIDNEY IN 24 HOURS

(AMOUNTS IN GRAMS)

           SUBSTANCE     AMOUNT FILTERED AMOUNT REABSORBED     AMOUNT IN URINE
WATER 180 LITERS 179 LITERS 1 LITER
PROTEINS 10 TO 20 10 - 20 0
CHLORIDE 630 625 5
SODIUM 540 537 3
BICARBONATE 300 299.7 0.3
GLUCOSE 180 180 0
UREA 53 28 25
POTASSIUM 28 24 4
URIC ACID 8.5 7.7 0.8
CREATININE 1.4 0 1.4

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HISTOLOGY OF THE URINIFEROUS TUBULE

The basic functional unit of the kidney is the uriniferous tubule. This is a continuous tubule which can be divided into a nephron (3 to 4cm in length) and a collecting duct (2cm long). Each collecting duct receives urine from several nephrons and carries the urine through a renal pyramid to the renal pelvis.

THE NEPHRON

Renal Corpuscle - The nephron begins as a blind, cup-like pocket called Bowman’s capsule. The capsule envelopes a bundle of capillaries called the glomerulus. The capsule and the glomerulus make up the renal corpuscle. Blood enters the glomerulus by an afferent arteriole and leaves via an efferent arteriole of smaller diameter. The difference in the diameters of these vessels leads to a rise in blood pressure in the glomerulus. As a result, the blood moving through the glomerulus loses a great deal of water, glucose and electrolytes (especially Na+ and Cl-) to the capsule by filtration.

In order to facilitate this process of filtration, the capillary walls (endothelium) and the inner wall of Bowman’s capsule (visceral portion) are specially adapted. The endothelial cells have numerous pores or fenestrations (80nm in diameter). The inner or visceral portion of Bowman’s capsule wraps each capillary with a sheet of very unique cells called podocytes. Each podocyte has a cell body or perikaryon with a number of foot-like extensions or pedicels. The pedicels of adjacent podocytes interdigitate and adhere to the basal lamina of the endothelial cells. The fenestrated endothelial cell, basal lamina and layer of podocytes form the filtration membrane. The parietal or outer portion of Bowman’s capsule consists of simple squamous cells.

Proximal Convoluted Tubule - is the longest and widewst segment of the nephron. It has a length of about 14mm and a diameter between 40 to 60 um. The apical surfaces of the cuboidal epithelial cells of the tubule have an extensive brush border.

Loop of Henle - The cells of the descending limb of the loop are simple squamous and give this region of the tubule a narrow diameter. These cells are freely permeable to water. As the loop moves into its ascending portion, the cells become cuboidal (thick segment) and impermeable to water.

Distal Convoluted Tubule - Following the loop, the nephron continues as the distal tubule. The cells here are shorter than those in the proximal tubule and lack microvilli. As a result, the distal portion appears to have a wider lumen. The absence of microvilli supports the findings that reabsorption is not a primary activity of the distal tubule. A principal role is secretion of toxic materials (urea, ammonia, hydrogen ions) into the urine from the blood in the peritubular capillaries. The presence of an abundance of mitochondria in the cells of the distal tubule attest to the energy demanding nature of the secretory process.

Collecting Duct - There is a gradual transition between the end of the distal tubule and the collecting duct. Two types of cells are found lining the walls of the collecting ducts:

1. Principal cells are low cuboidal cells with a central nucleus and a pale staining cytoplasm.

2. Interspersed between the principal cells are Dark Intercalated cells. The cytoplasm of these cells stains more intensely and contains large numbers of mitochondria immediately around the nucleus. The dark cells also show more microvilli than the principal cells.

Juxtaglomerular Complex - consists of adjacent cells of the afferent arteriole, distal tubule and intervening cells of the extraglomerular mesangium.

1. Juxtaglomerular cells are deived from modified smooth muscle cells of the tunica media of the portion of the afferent arteriole adjacent to the distal tubule. These cells show a number of characteristics:

a. Cells appear to be epithelial.

b. Nuclei are spherical.

c. The cytoplasm contains prominent granules containing the enzyme, renin.

d. Electron microscopy shows an extensive rough ER and large Golgi apparati.

e. There is no elastic lamina separating the juxtaglomerular cells from the endothelium of the afferent arteriole.

2. Macula densa is found in the wall of the distal tubule adjacent to the afferent arteriole. The region appears as a "dense spot" because the cells in this part of the tubule are narrower and their nuclei are closely packed together. There is no basal lamina separating these cells from the afferent arteriole.

3. A collection of cells can be found between the macula densa, afferent arteriole and efferent arteriole. This aggregate is called the Extraglomerular mesangium. Its function is not well understood.