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Chapter 4 Renal Function

Chapter 4 Renal Function. Dr Atef A Masad. What do the kidneys do?. Urine formation Regulate body fluid osmolality and volume Regulate electrolyte balance Regulate acid-base balance Excrete waste products and foreign substances

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Chapter 4 Renal Function

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  1. Chapter 4Renal Function Dr Atef A Masad Renal Function

  2. What do the kidneys do? • Urine formation • Regulate body fluid osmolality and volume • Regulate electrolyte balance • Regulate acid-base balance • Excrete waste products and foreign substances • Produce and excrete hormones such as Erythropoietin and Rennin Renal Function

  3. The kidneys are a pair of fist-sized organs that are located on either side of the spinal column just behind the lower abdomen (L1-3). • The kidney is a component of the urinary tract system, which consists of kidneys, ureters, urinary bladder, and urethra. • The urinary tract functions as a pathway for the elimination of metabolic by-products and unessential chemicals and removal of potentially toxic waste products. Renal Function

  4. Renal anatomy Cortex Pelvis Capsule Medulla To the bladder Renal Function

  5. The kidney maintains the water, ionic, and chemical balance of blood by filtering chemicals from the blood and conserving, or reabsorbing, those chemicals that are needed for adequate metabolism. • The kidneys maintain the balance of plasma constituents, while excreting those substances that are no longer needed by the body. Renal Function

  6. The central portion of the kidney consists of tubules that drain the kidney cortex and medulla. • The cortex, or outer portion of the kidney, appears red and contains the blood vessels, which bring blood to the kidney, and nephrons, the functional units that filter and maintain the chemical stasis of the blood. • The medulla appears as a series of pyramids within the cortex and contains straight tubules and collecting ducts. Renal Function

  7. There are about 1 million nephons in each kidney. • In association with blood vessels that serve the kidney, the nephrons make up the cortex and medulla of the kidney. • Each nephron contains a glomerulus, proximal tubule, loop of Henle, distal tubule and collecting duct. • The glomerulus filters blood plasma from arterioles into Bowman’s space and hence in the proximal tubule of the nephron. Renal Function

  8. Proximal tubule Afferent arteriole Distal tubule Glomerulus Bowman’s capsule Collecting duct Renal artery Henle’s Loop The Nephron Renal Function

  9. Renal Physiology • 3 basic renal processes • Glomerular filtration, • Tubular reabsorption, • Tubular secretion. • Glomerular filtration • Glomerulus filters incoming blood, all substances except cells and large molecules pass into further sections of the nephron. • Filtration process requires adequate pressure. • Water, electrolytes, glucose, amino acids, urea, creatinine pass freely and enter the proximal tubule. Renal Function

  10. The integrity of the glomerulus membrane, which consists of the endothelium, basement membrane, and epithelium, and renal blood flow determine the glomerular filtration rate. • The glomerulus has multiple small pores through which chemicals are filtered from the blood. • In a healthy kidney, the pores exclude any substance with a molecular radius more than 4 nm. • The glomerulus also selects by charge. • Substances that are neutral or have positive charge are more likely to pass through the pores of the glomerulus than substances that are negatively charged. Renal Function

  11. For example, albumin, which has a molecular radius of less than 4 nm but is negatively charged, does not readily pass through the pores of the glomerulus. • In a healthy kidney, cellular blood components should be excluded from the filtrate because of their size. • Albumin, many plasma proteins, cellular elements, protein-bound substances such as lipids and bilirubin are stopped. Renal Function

  12. "GFR" • The kidneys receive each minute 1500-2000 ml of blood, the glomerulus filters out 125-130 ml protein and cell free. • The volume of blood filtered per minute is known as the glomerulus filtration rate Renal Function

  13. Mean capillary blood pressure = 50 mm Hg BC pressure = 10 mm Hg Onc. pressure = 30 mm Hg Net hydrostatic = 10 mm Hg Glomerular filtration Glomerlular capillary membrane Vascular space Bowman’s space  2,000 Liters per day (25% of cardiac output)  200 Liters per day GFR  130 mL/min Renal Function

  14. Then what happens? • If 200 liters of filtrate enter the nephrons each day, but only 1-2 liters of urine result, then obviously most of the filtrate (99+ %) is reabsorbed. • Reabsorption can be active or passive, and occurs in virtually all segments of the nephron. Renal Function

  15. Reabsorption from glomerular filtrate Renal Function

  16. What gets filtered in the glomerulus? • Some filtered • 2-microglobulin • 1-microglobulin • Albumin • None filtered • Immunoglobulins • Ferritin • Cells • Freely filtered • H2O • Na+, K+, Cl-, HCO3-, Ca++, Mg+, PO4, etc. • Glucose • Urea • Creatinine • Insulin Renal Function

  17. Proximal Convoluted Tubule • It returns valuable substances back to the blood circulation, this includes ¾ of the water. • Renal threshold for each substance determines whether it is reabsorbed or secreted. • However, some substances have no renal threshold e.g H2O. • Proximal tubule secrets products of kidney tubular cell metabolism such as H+ Renal Function

  18. Reabsorption may be active or passive • Active — against a concentration gradient (glucose, amino acids, low mw proteins, sodium, etc.) — • regulated by the kidney according to the level of these substances in the blood • Passive — no energy involved — such as water and urea • Tubular secretion may also be passive or active

  19. Henle's Loop • The hyperosmolality (solute concentration ) is maintained by the Henle's loop. • The descending limb is permeable to water but not to solute. • Passive reabsorption of water in descending loop • The ascending limb is impermeable to water but permeable to Na, Cl and partially permeable to urea. • The medullary interstitial fluid becomes hyperosmotic compared to the fluid in the ascending limb. • The high osmolality of the surrounding interstitial medulla fluid is the physical force that accelerates the absorption of water from the descending limb. Renal Function

  20. Na+ 300 mOsm/Kg H2O Increasing osmolality Na+ Na+ 1200 mOsm/Kg The Loop of Henle Proximal tubule Distal tubule Renal Cortex Descending loop Ascending loop Renal Medulla Renal Function

  21. The interstitial hyperosmolality is maintained because the ascending limb continues to pump Cl– and Na+ ions into it. • The net result is production of hypoosmolal urine as it leaves the loop. • This process is called countercurrent multiplier system. Renal Function

  22. Distal Convoluted Tubule • Small adjustments occur to achieve electrolyte and acid-base homeostasis. • It is under the control of aldosterone. • Aldosterone stimulates Na+ reabsorption by distal tubule and K and H+ ion secretion. • H+ ions secretion is linked to bicarbonate regeneration and ammonia secretion which occur here, small amounts of Cl– are reabsorbed. Renal Function

  23. Collecting Duct • Is the final site for either concentrating urine or diluting it. • The upper portion is under the control of aldosterone which acts to stimulate Na reabsorption. • Cl and urea are absorbed here. • The collecting duct is under the control of ADH which stimulates water reabsorption. Renal Function

  24. Renal Function

  25. Water Balance • Water loss is under the control of ADH. • ADH responds primarily to changes in osmolality and intravascular volume. • Increased osmolality stimulates ADH secretion which increases the permeability of collecting tubules to water resulting in more concentrated urine. • In dehydration, reabsorption of water is increased, • In states of water excess, tubules reabsorb water at only a minimal rate resulting in excretion of large volume of dilute urine. Renal Function

  26. Plasma hyperosmolality H2O H2O ADH (vasopressin) Regulation of H2O reabsorption Pituitary Renal Medulla (osmolality 1200 mOsm/Kg) Renal Function

  27. Acid-Base Balance • The renal system participates in controlling body pH in addition to respiratory system and the acid-base buffering system. • The kidneys role in controlling body pH is accomplished by preserving HCO3– and removing metabolic acids. Renal Function

  28. Regeneration of HCO3– • HCO3– are filtered by the glomerulus. • HCO3– combines with H+ in the lumen of renal tubules to form H2CO3. • H2CO3 is degraded to CO2 + H2O. • CO2 diffuses into proximal tubules and is converted to H2CO3 by the action of carbonic anhydrase, then it is degraded back to H+ and HCO3. • This regenerated HCO3 is transported into the blood to replace the depleted one by metabolism, H+ are secreted into the tubular lumen and enter the urine. Renal Function

  29. Reaction with NH3 • NH3 is formed in the renal tubules as a result of glutamine deamination by glutaminase, NH3 then react with H+ to form NH4 which is excreted in urine. • Glutaminase • Glutamine  glutamic acid + NH3 • NH3 + H+ + NaCl  NH4 Cl + Na+ • This mode of acid excretion is the primary means by which the kidneys compensate for states of metabolic acidosis. Renal Function

  30. Reaction with Monohydrogen phosphate "HPO42– • Phosphate ions filtered by glomerulus exist in tubular fluid as Na2HPo4 which can react with H+ to yield NaH2 Po4 + Na. • Na2HPo4 is excreted, it is responsible for the titratable acidity of the urine. • The released Na combines with HCO3– to yield NaHCO3 which is reabsorbed. Renal Function

  31. Sodium is exchanged in the presence of the hormone aldosterone and water is exchanged in the presence of antidiuretic hormone (ADH). • The exchange of chemicals back into the blood supply is called reabsorption. • Exchange may occur as active transport, or as passive transport, which occurs with the gradient from high to low concentration of the chemical. • Some tubule cells, especially those in the distal portion of the nephron, exchange sodium and water back into the blood supply. Renal Function

  32. Because of the ability of the nephron to filter and reabsorb certain chemicals from the blood, the measurement of the concentration of these chemicals in the blood and urine serves as a functional evaluation of the kidney and specific areas of the nephron. • The measurements of the concentrations of creatinine, blood urea nitrogen, and electrolytes all serve as functional evaluations of different areas of the kidney. Renal Function

  33. Renal Endocrine Function • (A) Primary endocrine function • The kidneys synthesize rennin, prostaglandin and erythropoietin. • 1- Rennin • Rennin is produced by renal medulla whenever extracellular fluid volume decreases. • It is responsive to changes in Na+ and K+ levels in blood. Renal Function

  34. It is vasoconstrictor which increases blood pressure. • It catalyzes the synthesis of angiotensin by means of cleavage of the circulating plasma precursor angiotensinogen.

  35. Angiotensinogen  Na+ Renin  BP Angiotensin I Angiotensin II vasoconstriction Angiotensin III Adrenal cortex Aldosterone Na+ Na+ Regulation of distal tubule Na+ permeability Renal Function

  36. ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure, ACEangiotensin converting enzyme Renal Function

  37. Atrial natriuretic peptide (ANP), is a powerful vasodilator hormone secreted by heart muscle cells. ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood pressure Renal Function

  38. 2- Prostaglandins • Prostaglandins produced by kidneys increase renal blood flow, Na and H2O excretion and rennin discharge. • They resist renal vasoconstriction due to angiotensin and norepinephrine. • Prostaglandins are used in antihypertensive therapy.

  39. 3- Erythropoietin • It is a single chain polypeptide. • It is produced by cells close to the proximal tubules. • Its production is regulated by blood oxygen levels "hypoxia increases its production". • Erythropoietin acts on the erythroid progenitor cells in the bone marrow, causing their maturation and increasing the number of RBCs. • In chronic renal insufficiency, erythropoietin production is significantly reduced causing anemia. Renal Function

  40. (B) Secondary Endocrine Function • The kidneys are the target locus for the action of aldosterone, the catabolism of insulin, glucagons and aldosterone and as a point of activation of vitamin D metabolism. Renal Function

  41. Renal Disorders Acute Glomerulonephritis Nephrotic Syndrome Tubular Diseases Urinary Tract Infection Acute Renal Failure 41 M. Zaharna Clin. Chem. 2009

  42. Acute Glomerulonephritis Red cell cast Acute inflammation of the glomeruli Results in oliguria, hematuria, increased BUN and serum creatinine, decreased GFRand hypertension Red cell cast finding are of great importance Proteinuria also present 42 M. Zaharna Clin. Chem. 2009

  43. Nephrotic Syndrome Massive proteinuria, edema, hypoalbuminemia, hyperlipidemia, and lipiduria Has many cuases Characterized by increased glomerular membrane permeability — loss of protein (greater than 2-3 grams per day) 43 M. Zaharna Clin. Chem. 2009

  44. Tubular Diseases Depressed secretion or reabsorption of specific biochemicals Or Impairment of urine dilution and concentration mechanisms Renal Tubular Acidosis — most important Low values of phosphorus in serum, and presence of glucose and AA in urine 44 M. Zaharna Clin. Chem. 2009

  45. Urinary Tract Infection Bladder — cystitis Kidneys — pyelonephritis Bacterial concentrations >100,000 colonies/mL Increased number of white blood cells Increased number of red blood cells may be present White blood cell casts is considered diagnostic of pyelonephritis 45 M. Zaharna Clin. Chem. 2009

  46. Acute Renal Failure • Ocurring when the GFR is reduced to less than 10 mL/minute. • Prerenal — before blood reaches the kidney • Hypovolemia • Cardiovascular failure • Renal — occuring in kidney • Acute tubular necrosis • Glomerulonephritis • Postrenal — after urine leaves kidney • Obstruction 46 M. Zaharna Clin. Chem. 2009

  47. Usually accompanied by oliguria Associated with varying degrees of proteinuria, hematuria, and presence of red cell casts and other casts BUN and creatinine increase rapidly Can progress to chronic renal insufficiency or failure 47 M. Zaharna Clin. Chem. 2009

  48. Renal Calculi • Formed by the combination of various crystallized substances. • Such as Ca-phospahte, Uric Acid, Cystine, Mg-ammonium phosphate and Ca-oxalate • Calcium oxalate stones are the most common. • Formed due a reduced urine flow rate due to decrease fluid intake and urine saturation of insoluble substances, ifections, Gout, inherited diseases, Hyperparathyroidism, high urine Ca, Vitamin D toxicity

  49. Chemical analysis is available and x ray diffraction. • Clinical symptoms: hematuria, UTI, and abdominal pain

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