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Physiology of kidney
- 6. GLOMERULAR FILTRATION RATE(GFR) •The level of urea depends both on GFR and its production rate.This is influenced by protein intake and tissue catabolism. • The creatinine level is much less dependent but is more related to age,sex and muscle mass. • Serum creatinine is better guide to GFR than urea and good way to monitor futher deterioration in the GFR
- 7. 1. creatinine clearance 2.Calculated GFR • Cockcroft-Gault equation • Modification of diet in renal disease (MDRD) equation • CKD Epidemiology (CKD-EPI) collaboration equation U x VP (U=Urine concentration of creatinine. V = rate of urine flow in mL/min , P = plasma concentrarion of creatinine) Normal ranges : 90-140 mL/min in men, 80-125 mL/min in female
- 9. TUBULAR FUNCTION • Selectivereabsorption or excretion of water and various cations and anions to keep the volume and electrolyte composition of body fluid normal
- 10. FLUID AND ELECTROLYTEBALANCE Water balance • Water balance : input = output • Direct control of water excretion in the kidneys is exercised by : – vasopressin, or anti-diuretic hormone (ADH). – ADH causes the insertion of water channels into the membranes of cells lining the collecting ducts, allowing water reabsorption to occur => lowering osmolarity (reducing sodium concentration), helpto dilute bodily fluids. – To prevent osmolarity from decreasing below normal, the kidneys also have a regulated mechanism for reabsorbing sodium in the distal nephron. This mechanism is controlled by aldosterone, The adrenal cortex directly senses plasma osmolarity. When the osmolarity increases above normal, aldosterone secretion is inhibited. Activation of Renin angiotensin aldosterone system (RAAS)
- 12. URINE CONCENTRATION ANDTHE COUNTERCURRENT SYSTEM • The loop of Henle acts as a countercurrent multiplier that uses energy to create concentration gradients. The descending limb is water permeable. Water flows from the filtrate to the interstitial fluid, so osmolality inside the limb increases as it descends into the renal medulla. At the bottom, the osmolality is higher inside the loop than in the interstitial fluid. Thus, as filtrate enters the ascending limb, Na+ and Cl- ions exit through ion channels present in the cell membrane. Further up, Na+ is actively transported out of the filtrate and Cl- follows. Osmolarity is given in units of milliosmoles per liter (mOsm/L).
- 13. Sodium balance • Inaddition to regulating total volume, the osmolarity of bodily fluids is also tightly regulated. Extreme variation in osmolarity causes cells to shrink or swell, damaging or destroying cellular structure and disrupting normal cellular function. • Regulation of osmolarity is achieved by balancing the intake and excretion of sodium with that of water • An important concept is that regulation of osmolarity must be integrated with regulation of volume, because changes in water volume alone have diluting or concentrating effects on the bodily fluids.
- 14. ACID-BASE BALANCE • Thekidneys have two very important roles in maintaining the acid-base balance: 1. to reabsorb bicarbonate from urine 2. to excrete hydrogen ions into urine.
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- 17. ENDOCRINE FUNCTION • RENIN-ANGIOTENSINSYSTEM JUXTAGLOMERULAR APPARATUS: • Renin converts angiotensinogen to angiotensin II • Renin released is controlled by: 1. Pressure changes in afferent arteriole 2. Sympathetic tone 3. Chloride and osmotic concentration in distal tubule via the macula densa 4. Local prostaglandin and nitric oxide release
- 19. ERYTHROPOIETIN • Loss ofrenal substance,results in normochromic,normocytic anaemia • Conversely,erythropoietin secretion is increased in polycystic kidney,benign renal cysts or renal cell carcinoma
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- 21. AUTOCRINE FUNCTION ENDOTHELIN • Thevascular actions are mediated by 2 receptors ETA for vasocontriction and ETB causing vasodilation. • Function : Inhibits sodium and water absorption by suppressing Na+/K-ATPase and Na+/H+ antiporter activity in prox tubule • Antagonize the action of ADH and aldosterone in the collecting duct.
- 22. PROSTAGLANDIN • COX-1 expressedin collecting duct • COX-2 is restricted in macula densa • COX convert arachidonic acid to prostaglandin H2 VC ,mainly synthesized in glomerulus Produced in prox tubule Produce in collecting duct,responsible for natriuretic and diuretic peptide Mainly synthesized in the interstitial and vascular compartment
- 23. NATRIURETIC PEPTIDE Significant rolein cardiovascular and fluid homeostasis BNP -Found in ventricle and brain -Exceed in congestive heart failure ANP -Secreted from atrial granules in response to atrial stretch. -Increase sodium and water excretion and GFR -Direct VD,reduces renin release and aldosterone secretion and inhibits angiotensin II
- 24. NITRIC OXIDE ANDTHE KIDNEY ACTIONS IN THE KIDNEY • Regulation of renal hemodynamics • Natriuresis by inhibiting Na+/K+-ATPase and Na+/H+ antiporter and antagonizing ADH