Physiologic Anatomy of the Kidneys PDF

Physiologic Anatomy of the Kidneys General Organization of the Kidneys and Urinary Tract The two kidneys lie on the posterior wall of the abdomen, outside the peritoneal cavity.Each kidney of the adult human weighs about 150 grams. The medial side of each kidney contains an indent...

Physiologic Anatomy of the Kidneys General Organization of the Kidneys and Urinary Tract The two kidneys lie on the posterior wall of the abdomen, outside the peritoneal cavity.Each kidney of the adult human weighs about 150 grams. The medial side of each kidney contains an indented region called the hilum through which pass the renal artery and vein, lymphatics, nerve supply, and ureter, which carries the final urine from the kidney to the bladder, where it is stored until emptied. The kidney is surrounded by a tough, fibrous capsule that protects its inner structures called the renal capsule. Gross structure of the kidney: Longitudinal section of a kidney shows an outer reddish granular layer called the renal cortex & an inner striated paler part called the renal medulla. In the renal medulla, there are triangular, wedge-shaped structures called the renal pyramids. The tips of the pyramids form the renal papillae at which urine is drained into cavities called renal calyces which drain urine into the renal pelvis, then to the ureter. (Figure1) Fig.1 General Organization of the kidney and the urinary system Hall: Guyton and Hall Text book of Medical Physiology, 12th Edition The nephron is the functional unit of the kidney each kidney in the human contains about 800,000 to 1,000,000 nephrons, each capable of forming urine. The kidney cannot regenerate new nephrons. Therefore, with renal injury, disease, or normal aging, there is a gradual decrease in nephron number. Nephron consists of two main parts: The renal corpuscle & the renal tubule (Figure2). (I) Renal (Malpighian) corpuscle: 1. Glomerulus: a tuft of glomerular capillaries, through which large amounts of fluid are filtered from the blood. The glomerulus contains a network of branching and anastomosing glomerular capillaries. The glomerular capillaries are covered by epithelial cells, and the total glomerulus is encased in Bowman’s capsule. 2- Bowman’s capsule: It is formed by two layers: an internal permeable visceral layer that directly overlies the glomerular capillaries, and an external impermeable parietal layer composed of simple squamous epithelium. Between these two layers is a capsular space that receives the filtrate, which is then modified to form urine. It opens into the proximal convoluted tubule (PCT). (II) Renal tubule: long tubule in which the filtered fluid is converted into urine on its way to the pelvis of the kidney. Fluid filtered from the glomerular capillaries flows into Bowman’s capsule and then into the proximal tubule, which lies in the cortex of the kidney. From the proximal tubule, fluid flows into the Loop of Henle, which dips into the renal medulla. Each loop consists of a descending and an ascending limb. Then fluid enters the distal tubule, which like the proximal tubule, lies in the renal cortex. This is followed by, the connecting tubule and the cortical collecting tubule, which lead to the cortical collecting duct. The initial parts of 8 to 10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the medulla and becomes the medullary collecting duct. The collecting ducts merge to form progressively larger ducts that eventually empty into the renal pelvis through the tips of the renal papillae.  Fig. 2 Basic tubular segments of the nephron Hall: Guyton and Hall Text book of Medical Physiology, 12th Edition  Regional Differences in Nephron Structure Cortical and Juxtamedullary Nephrons: Although each nephron has all the components described earlier, there are some differences, depending on how deep the nephron lies within the kidney mass. (Figure 3) Cortical nephrons: Those nephrons that have glomeruli located in the outer cortex, constitute about 80% of the total number of nephrons and receive 90% of renal blood supply, they have short loops of Henle that penetrate only a short distance into the medulla, the entire tubular system is surrounded by an extensive network of peritubular capillaries. Juxtamedullary nephrons: About 20 to 30 percent of the nephrons have glomeruli that lie deep in the renal cortex near the medulla, they have long loops of Henle that dip deeply into the medulla, long efferent arterioles extend from the glomeruli down into the outer medulla and then divide into specialized peritubular capillaries called vasa recta that extend downward into the medulla, lying side by side with the loops of Henle. Like the loops of Henle, the vasa recta return toward the cortex and empty into the cortical veins. This specialized network of capillaries in the medulla plays an essential role in the formation of a concentrated urine. Fig.3 Schematic of relations between blood vessels and tubular structures and differences between cortical and juxtamedullary nephrons. Hall: Guyton and Hall Text book of Medical Physiology, 12th Edition.  Multiple Functions of the Kidneys 1. Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabolites The kidneys are the primary means for eliminating waste products of metabolism that are no longer needed by the body. These products include: A. urea is formed from the amino acid which are used for heat and energy. Before this occurs, the nitrogen part of the molecule is converted to ammonia and then to urea. B. creatinine in the urine comes from creatine in muscles, and its presence in the urine represents a loss of nitrogen from the body. C. uric acid the nitrogen from nucleic acids and purines is excreted in the form of uric acid. Some uric acid is synthesized in the body.an excessive production of this substance and its deposition in the joints lead to the painful condition of gout. D. bilirubin end products of hemoglobin breakdown. E. excretion of foreign substances that are either produced by the body or ingested, such as pesticides, drugs, and food additives. F. Excretion of toxic substances after its detoxication by conjugation & then excreted by the kidney. G. metabolites of various hormones. These waste products must be eliminated from the body as rapidly as they are produced. 2. Regulation of Water and Electrolyte Balances For maintenance of homeostasis, excretion of water and electrolytes must precisely match intake. Intake of water and many electrolytes is governed mainly by a person’s eating and drinking habits, requiring the kidneys to adjust their excretion rates to match the intakes of various substances. 3. Regulation of Arterial Pressure The kidneys play a dominant role in long-term regulation of arterial pressure by excreting variable amounts of sodium and water. The kidneys also contribute to short-term arterial pressure regulation by secreting hormones and vasoactive factors or substances (e.g., renin) that lead to the formation of vasoactive products (e.g., angiotensin II). 4. Regulation of Acid-Base Balance The kidneys contribute to acid-base regulation, along with the lungs and body fluid buffers, by excreting acids and by regulating the body fluid buffer stores. The kidneys are the only means of eliminating from the body certain types of acids, such as sulfuric acid and phosphoric acid, generated by the metabolism of proteins. 5. Regulation of Erythrocyte Production The kidneys secrete erythropoietin, which stimulates the production of red blood cells by hematopoietic stem cells in the bone marrow. One important stimulus for erythropoietin secretion by the kidneys is hypoxia. The kidneys normally account for almost all the erythropoietin secreted into the circulation. In people with severe kidney disease or who have had their kidneys removed and have been placed on hemodialysis, severe anemia develops as a result of decreased erythropoietin production. 6. Regulation of 1, 25-Dihydroxyvitamin D3 Production The kidneys produce the active form of vitamin D, 1, 25-dihydroxyvitamin D3 (calcitriol), by hydroxylating this vitamin at the “number 1” position. Calcitriol is essential for normal calcium deposition in bone and calcium reabsorption by the gastrointestinal tract. Calcitriol plays an important role in calcium and phosphate regulation. 7. Glucose Synthesis The kidneys synthesize glucose from amino acids and other precursors during prolonged fasting, a process referred to as gluconeogenesis. With chronic kidney disease or acute failure of the kidneys, these homeostatic functions are disrupted and severe abnormalities of body fluid volumes and composition rapidly occur. With complete renal failure, enough potassium, acids, fluid, and other substances accumulate in the body to cause death within a few days, unless clinical interventions such as hemodialysis are initiated to restore, at least partially, the body fluid and electrolyte balances. Renal circulation Characteristics of renal circulation: 1. Almost, all renal blood has to pass through the glomeruli. 2. Renal circulation is a portal circulation i.e. blood circulates in to two capillary networks: the glomerulus and peritubular capillaries. The glomerular capillaries are the only capillaries in the body that drain in to arterioles. The efferent glomerular arteriole is a portal artery. The portal renal system has 2 functions: A. filtration through the glomerular capillaries. B. Reabsorption and secretion through the peritubular capillaries. 3. The kidney have a high blood flow rate. The kidney receives about 1300 ml of blood/min. [20 – 25 % of CO]. The high renal blood flow does not reflect high O2 consumption; kidney utilize 8% of the total O2 consumption of the body. The high renal blood flow is related to the homeostatic function of the kidney which allows a high rate of glomerular filtration, i.e. out of 700 ml of plasma flowing through the glomeruli 120 ml are filtered in to capsule; 99% of the filtrate is reabsorbed by renal tubules leaving behind unwanted substances to be excreted in urine. 4. Renal blood pressure is comparatively high because: - - The renal artery is short & wide & arise directly from aorta. - The afferent glomerular vessel is wider & shorter than the efferent vessel. Fig. 4 Section of the human kidney showing the major vessels that supply the blood flow to the kidney and schematic of the microcirculation of each nephron.  Pressure in the renal circulation The two major areas of resistance to blood flow in the nephron are the afferent and efferent arteriole. In the afferent arteriole the pressure falls from 100mmHg at its arteriole end to a mean pressure of about 60 mmHg in the glomerulus. As blood flows through the efferent arteriole from the glomerulus to the peritubular capillary system, the pressure falls another 47 mmHg to a mean peritubular capillary pressure of about 13 mmHg. Thus, the high pressure capillary bed in the glomerulus acts at a mean pressure of about 60 mmHg which causes rapid filtration of fluid in to Bowman’s capsule. On the other hand, the low pressure capillary bed in the peritubular capillary system acts at a mean capillary pressure of about 13 mmHg which allows rapid absorption of fluid because of high osmotic pressure of plasma. (Figure 5) Fig.5 Pressure in renal circulation  Formation of urine Urine is formed by 3 main processes (figure 6): A. Glomerular filtration B. Tubular reabsorption C. Tubular secretion Fig6. Basic kidney processes that determine the composition of the urine. Urinary excretion rate of a substance is equal to the rate at which the substance is filtered minus its reabsorption rate plus the rate at which it is secreted from the peritubular capillary blood into the tubules. A. Glomerular filtration: Glomerular filtration is the first step in urine formation. The urine is formed by simple filtration of the plasma in the glomeruli into Bowman’s capsule. The glomerulus acts as a filter between the blood and the tubule. The filtration is passive process and the driving force of this filtration is high capillary blood pressure in the glomeruli. The fluid that filters through the glomeruli in to Bowman’s capsule is called Glomerular filtrate. This filtrate is plasma minus its colloids (fats & proteins). N.B: Glomerular filtrate rate (GFR) The total amount of filtrate formed by the kidneys per minute is referred to as the glomerular filtration rate (GFR). The units of filtration are a volume filtrated per unit time, e.g. ml/min or liters/day. Normal value is 125 ml/min or 180 liters/day. 99% of filtrate is reabsorbed by renal tubules. 1% passes into urine. The glomerular capillary membrane: It is a passive semi-permeable membrane through which the plasma is filtered, despite the number of layers it has a high permeability and is estimated to be 100-500 times the permeability of usual capillary. It consists of the following 3 layers (Figure7): 1- Endothelium of glomerulus: The capillary endothelial cells lining the glomerulus are perforated by thousands of small holes called fenestrae which allow plasma and its dissolved substances to be filtered, while restricting the passage of large structures, such as (erythrocytes, leukocytes, and platelets). 2- Basement membrane of glomerulus: This is a gel like structure composed of a meshwork of fine fibrils (collagen & glycoproteins). It appears poreless but in fact it contains spaces through which fluid filtration can occur. The glycoproteins prevent the filtration of small plasma proteins (albumin) because the glycoproteins are negatively charged, they repel albumin and other plasma proteins, which are also negatively charged. In nephritis, the negative charges in the glomerular wall are dissipated, and albuminuria can occur for this reason without an increase in the size of the “pores” in the membrane. 3- Visceral layer of Bowman’s capsule (= podocytes): This layer consists of epithelial cells (podocytes) which don’t form a continuous layer. Podocytes are octopus-like cells that have long, “foot-like” processes called pedicels that wrap around the glomerular capillaries. The space between adjacent foot processes, called a filtration slit, is about 40 nm wide. Such epithelium has no function either in reabsorption or secretion and acts only as filter, restricting the passage of large molecules of molecular weight more than 70,000. Fig 7. A, Basic ultrastructure of the glomerular capillaries. B, Cross section of the glomerular capillary membrane and its major components: capillary endothelium, basement membrane, and epithelium (podocytes). Dynamics of glomerular filtration: (Fig. 8) 1) Filtration forces: a- The hydrostatic glomerular capillary pressure (60 mm Hg). b- The colloidal osmotic pressure of proteins in Bowman’s capsule (0). 2) Reabsorption forces: a- The colloidal osmotic pressure of plasma proteins in glomerular capillaries (32 mm Hg). Approximately one fifth of the plasma in capillaries filters in to capsule thus the concentration of plasma proteins increase about 20 % as blood passes from arteriolar to the venous ends of the glomerular capillaries. If the normal colloid osmotic pressure of blood entering the capillaries is 28 mmHg, it rises to approximately 36 mmHg by the time the blood reaches the venous ends of the capillaries, and the average colloid osmotic pressure is about 32 mmHg. b- The hydrostatic capsular pressure (18 mm Hg). 3) The net filtration pressure (NFP): = (60 + 0) – (32 + 18) = 10 mm Hg. Fig 8. Summary of forces causing filtration by the glomerular capillaries. The values shown are estimates for healthy humans. GFR depends on: )1) Balance of hydrostatic and colloid osmotic forces )2) Capillary filtration coefficient Kf (permeability and area of glomerular membrane). Therefore, the GFR is equal to the NFP× Kf. The filtration coefficient (Kf): It is the GFR for both kidneys per mmHg of net filtration pressure. (Kf) the product of the permeability × filtering surface area. A high value indicates a high permeable capacity. A low value indicates a low permeable capacity. The Kf = GFR/ NFP ie.125 ml/min ÷ 10 mm Hg =12.5 ml/min/mm Hg. The high rate of glomerular filtration (180 liters are filtered per day. As plasma volume is about 3 liters, plasma filtered by the kidney 60 times a day) is due to: 1- High capillary blood pressure, higher than any other capillary in the body, due to the special arrangement of the renal arterial system: a) The renal artery is short, wide and arises directly from aorta, this leads to high pressure in the afferent glomerular arteriole. b) The afferent glomerular vessel is wider and shorter than the efferent arteriole. 2- High glomerular filtration coefficient (Kf) which depends upon: a) The surface area of the glomerular membrane. b) The permeability of the filtrating membrane. The total surface area of the glomerular membrane is 2 square meters. The permeability of the filtrating membrane is very high. Factors affecting the GFR: [A] The hydrostatic glomerular capillary pressure (GCP): ⬆GCP➡ ⬆ GFR & vice versa Factors that affect the GCP: 1. The renal blood flow (RBF): An increase in the rate of blood flow through the nephrons greatly elevates the glomerular pressure and increase the GFR. ⬆RBF ➡ ⬆GCP➡ ⬆ GFR & vice versa. Normally, a very large amount of plasma is filtrated through glomerular membrane; thus, the colloid osmotic pressure in the glomerular rises very high and opposes furthered filtration because of the retained colloids. Filtration stops until new plasma flows in to the glomerulus; consequently, the greater the rate of plasma flow in the glomerulus, the greater is the filtration rate. 2. Diameter of glomerular blood vessels: I. Afferent glomerular arteriole: A. Arteriole dilatation increase the glomerular blood flow and glomerular pressure; both effects increase the filtration rate. VD ➡⬆RBF ➡⬆GCP ➡⬆GFR. B. Arteriole constriction decreases the rate of blood flow into the glomerulus, decrease the glomerular pressure and thus, decrease the filtration rate. VC ➡⬇RBF ➡⬇GCP ➡⬇GFR. II. Efferent glomerular arteriole: A. Arteriole dilatation lowers the glomerular pressure and decrease the filtration rate. VD ➡⬇ GCP ➡⬇GFR. B. Arteriole constriction mild constriction increases the glomerular pressure and increases the filtration rate. Mild.VC ➡⬆ GCP➡⬆ GFR. Severe or moderate constriction decreases glomerular flow rate and decreases the filtration rate. Sever.VC ➡⬇GFR. 3. Sympathetic stimulation: During sympathetic stimulation e.g. stress conditions, the afferent arterioles are constricted, both renal blood flow and filtration decrease. With very strong stimulation, the glomerular blood flow and pressure are reduced so greatly that the urinary output can fall to zero. 4) Arterial blood pressure (ABP): Increase arterial pressure tends to raise GCP and therefore, to increase GFR. However, this effect is buffered by auto-regulatory mechanism prevents a significant rise in the glomerular pressure corresponding to arise in the systemic blood pressure. Automatic afferent arteriolar constriction occurs in a case of a high arterial pressure. However, glomerular filtration rate increases only few percent if the increase in blood pressure is not sever. i.e. - Mild physiological changes in ABP ➡ does not affect the GFR due to autoregulation mechanism. - Severe changes in ABP ➡ marked changes in GFR. [B] Colloid osmotic pressure: Normally it is about 32 mm Hg & antagonize the filtration. - ⬇ OP ➡ ⬇ GF as with nephrotic syndrome. - ⬆OP ➡ ⬆ GF as with multiple myeloma. [C] The hydrostatic capsular pressure: (Intrapelvic pressure) Arise of pressure in the renal pelvis will produce back pressure in the intracapsular pressure which antagonists the filtration force. A pressure higher than 28 mmHg will stop the filtration and consequently urine formation e.g. renal pelvic stone or tumors. [D] The glomerular capillary permeability: Normally, molecules with M Wt. more than 70,000 cannot pass through glomerular membrane. In case of plasma proteins, the serum albumin has M Wt. 70.000, globulin 165.000 and fibrinogen 200.000. Accordingly, serum globulin and fibrinogen cannot pass through, serum albumin can pass through, but the amount filtrated is very small, and therefore, it would be reabsorbed back in the renal tubules; normally urine is free of plasma protein. If the kidney becomes diseased, it's permeability and so serum albumin will appear in urine in large amounts. When the disease of the kidney is advanced. serum globulin will also appear in the urine. Fibrinogen will never appear. The M Wt. of hemoglobin is 68.000 but it is normally protected by being enclosed inside the membrane of RBCs. If hemolysis occurs, hemoglobin will be set free; and because of its M Wt. will pass through the glomeruli of kidney; this is dangerous because in the renal tubule the reaction is acidic and the hemoglobin will be precipitated as acid haematin which blocks the renal tubules leading to anuria and death. ⬆Permeability ➡ ⬆ GFR. As in fever, glomerulonephritis, hypoxia & nephrotoxic drugs. ⬇ Permeability ➡ ⬇GFR. As in uncontrolled diabetes mellitus & hypertension due to thickening of the glomerular capillary membrane. [E] Size of the glomerular capillary bed (the effective filtration surface area): The GFR is reduced if the glomerular surface area available for filtration is decreased as in chronic renal failure and after nephrectomy.