Renal physiological function
- 1. RENAL PHYSIOLOGICAL FUNCTION DR. PRERNA SINGH JUNIOR RESIDENT (3RD YEAR) DEPARTMENNT OF PHARMACOLOGY JNMCH AMU
- 2. General organization of kidney • Capsule • Cortex • Medulla • Pelvis • Renal artery and renal vein Source: Guyton and hall: Textbook of Medical Physiology
- 3. Nephron • Structural and functional unit of kidney • 1 Million in each kidney Source: Google images
- 4. Functions of kidney ◦ Excretory – metabolic products, drug, toxin ◦ Homeostatic - ◦ Water balance – BP regulation ◦ Electrolyte balance ◦ Acid base balance ◦ Liver detoxification ◦ Conservation of nutrients ◦ Endocrine ◦ Synthesis – erythropoietin, renin, prostaglandin ◦ Metabolic- D3 production ◦ Metabolic - gluconeogenesis
- 5. Excretory function • GFR- 20% OF RPF • GFR- 125ml/min • Rest goes to efferent – vasa recta • Filtration fraction- 𝐺𝐹𝑅 𝑅𝑃𝐹 • Protein free and devoid of cells Source: Guyton and hall: Textbook of Medical Physiology
- 6. Filtration layer 3 layered 1. Fenestrated endothelium • 70-90 nm pore • Negatively charged 2. Basement membrane • Negatively charged (proteoglycans) 3. Podocyte • 25nm slit Cross section of the glomerular capillary membrane Source: Guyton and hall: Textbook of Medical Physiology
- 7. Filterability Source: Guyton and hall: Textbook of Medical Physiology
- 8. Filtration pressure • High hydrostatic pressure in glomerular capillaries • Net filtration pressure- 10 mm Hg • GFR = Kf x Net filtration pressure Source: Guyton and hall: Textbook of Medical Physiology
- 11. PCT • Reabsorption of sodium and bicarbonate • Na/glucose CT • Na+/Pi CT • Na+ amino acid CT • Na/lactate CT • Na/H exchanger • Cl/base exchanger Source: Katzung Basic and Clinical Pharmacology
- 12. Loop of Henle • Sodium and chloride reabsorption • Na–K–2Cl CT • K+ channels Source: Katzung Basic and Clinical Pharmacology
- 13. Distal convoluted tubule • Sodium reabsorption • Calcium- under influence of PTH • NaCl CT Source: Katzung Basic and Clinical Pharmacology
- 14. Collecting tubule • Na+ channel (ENaC) Source: Katzung Basic and Clinical Pharmacology
- 15. Collecting tubule ◦ Aquaporins Source: Katzung Basic and Clinical Pharmacology
- 16. Water balance ◦ Passive reabsorption ◦ Facilitated by aquaporins Aquaporin 1 Luminal membrane PCT Aquaporin 2 Luminal membrane CD Aquaporin 3 Basolateral membrane CD Aquaporin 4 Basolateral membrane CD o PCT- 60-70% o LOH- 15% o DCT- 5% o CD- 15%
- 17. Free water clearance Free water: solute free water Negative free water clearance, indicates water conservation – urine concentrated Positive free water clearance, indicates excess water is being excreted by the kidneys – urine dilute
- 18. Water balance- BP control • Pressure diuresis- increased urine volume when pressure rises • Pressure natriuresis- increase sodium output when pressure rises Renal function curve Source: Guyton and hall: Textbook of Medical Physiology
- 19. Juxtaglomerular apparatus • Juxtaglomerular cells- renin • Macula densa – chemoreceptor cells • Lacis cell Source: Guyton and hall: Textbook of Medical Physiology
- 20. RAAS Renin released when arterial pressure is low Source: Guyton and hall: Textbook of Medical Physiology
- 21. Tubulo-glomerular feedback mechanism Source: Guyton and hall: Textbook of Medical Physiology
- 22. Electrolyte balance – Potassium • Extracellular K+ – 4.2mEq/L • Increase- arrhythmias • K regulation- 1. Redistribution between extracellular and intracellular compartment 2. Renal potassium excretion Principal cells of late distal tubule Collecting tubules • Absorbed as well as excreted Source: Guyton and hall: Textbook of Medical Physiology
- 23. Electrolyte balance – Potassium K secretion by Principal cells increased by Increased extracellular K+ Increased aldosterone Increased tubular flow rate Source: Katzung Basic and Clinical Pharmacology
- 24. Electrolyte balance – Potassium Increased intake increases excretion Source: Guyton and hall: Textbook of Medical Physiology
- 25. Electrolyte balance – sodium Site Transporter PCT- 60% Sodium hydrogen exchanger Thin ascending limb Passive – paracellular Thick Ascending Limb- 30% Na+ K+ 2Cl- DCT- 7% Na-Cl symporter CT -3% ENac Sodium reabsorption- In all parts except thin descending LOH Active reabsorption- except thin ascending portion (passive)
- 26. Electrolyte balance – Calcium Filtered and reabsorbed 65%- PCT 25% - LOH 4-9% - DCT, CT Not secreted Source: Guyton and hall: Textbook of Medical Physiology
- 27. Renal reabsorption of calcium PCT- Paracellular mostly 20% transcellular LOH- thick ascending limb Paracellular- repulsion by positive charge DCT- Active transport Source: Guyton and hall: Textbook of Medical Physiology
- 28. Acid base balance Balance between intake, production of H+ and removal of it Buffer system Respiratory control Renal control Normal concentration: 0.0004 mEq/L
- 29. Renal control of acid base balance • HCO3 - filtered and reabsorbed • H+ secreted • Buffers • Synthesis of new HCO3 -
- 30. Renal control of acid base balance • Active Secretion of H+ achieves Reabsorption of HCO3 - (Passive) in PCT • Sodium dependent secretion of H+ Source: Katzung Basic and Clinical Pharmacology
- 31. Late DCT • Hydrogen transporting ATPase • One HCO3 - absorbed for one H+ secreted • Sodium independent secretion of H+ Source: Guyton and hall: Textbook of Medical Physiology
- 32. Diphasic PO4 – buffer • Buffering of secreted hydrogen ions by filtered phosphate Source: Guyton and hall: Textbook of Medical Physiology
- 33. Ammonia buffer • Ammonia diffuses into the tubular lumen, where it reacts with secreted hydrogen ions to form NH4 + which is then excreted Source: Guyton and hall: Textbook of Medical Physiology
- 34. Generation of new HCO3 - • Glutamine➞ 2NH4+ + 2HCO3 - • The NH4+ is secreted by a Na+-NH4+ pump • For each glutamine molecule metabolized, two NH4+ are produced and secreted and two HCO3– are returned to the blood Source: Guyton and hall: Textbook of Medical Physiology
- 35. Synthesis of renin Renin – from JG cells of macula densa Stimulus – • Decreased renal flow • Decreased distal sodium • Beta 1 agonist • PGI2 Source: Guyton and hall: Textbook of Medical Physiology
- 36. Erythropoietin synthesis 90 per cent of all erythropoietin is formed in the kidneys; the remainder is formed mainly in the liver When both kidneys are removed or when the kidneys are destroyed by renal disease, the person invariably becomes very anaemic
- 37. Vitamin D3 activation In the proximal tubules 25-hydroxycholecalciferol is converted to 1,25- dihydroxycholecalciferol - most active form of vitamin D Requires PTH Source: Guyton and hall: Textbook of Medical Physiology
- 38. Gluconeogenesis During prolonged fasting, the kidneys also synthesize considerable amounts of glucose from amino acids and other precursors.
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