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STRUCTURE AND FUNCTIONS OF NEPHRON

Renal failure. STRUCTURE AND FUNCTIONS OF NEPHRON . Dr. WASIF ALI KHAN MD-PATHOLOGY (UNIVERSITY OF BOMBAY) Assistant Prof . in Pathology Al Maarefa College. Urinary System. Consists of Urine forming organs kidneys

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STRUCTURE AND FUNCTIONS OF NEPHRON

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  1. Renal failure STRUCTURE AND FUNCTIONS OF NEPHRON • Dr. WASIF ALI KHAN • MD-PATHOLOGY (UNIVERSITY OF BOMBAY) • Assistant Prof. in Pathology • Al Maarefa College

  2. Urinary System • Consists of • Urine forming organs • kidneys • Structures that carry urine from the kidneys to the outside for elimination from the body • Ureters • Urinary bladder • Urethra

  3. Urinary System

  4. Nephron • Functional unit of the kidney • Approximately 1 million nephrons/kidney • Each nephron has two components • Vascular component • Tubular component • Arrangement of nephrons within kidney gives rise to two distinct regions • Outer cortex • Renal cortex (granular in appearance) • Inner medulla • Renal medulla • Made up of striated triangles called renal pyramids

  5. The Nephron

  6. Nephron (Vascular component) • Dominant part is the glomerulus • Glomerulus is a tuft of glomerular capillaries. • large amounts of fluid & solutesare filtered from the blood.

  7. Juxtaglomerular apparatus

  8. Nephron (Tubular component) • Hollow, fluid-filled tube • single layer of epithelial cells • Components • Bowman’s capsule • Proximal convoluted tubule • Loop of Henle • Descending limb • Ascending limb • Juxtaglomerular apparatus • Distal convoluted tubule • Collecting duct or tubule

  9. Overview of kidney functions • Maintain H2O balance in the body. • Regulate the quantity and concentration of most ECF ions—Na, K, cl, Ca, Mg, ph. • Acid-base balance in the body • Excreting (eliminating) the end products (wastes) of bodily metabolism • Excreting many foreign compounds • Producing erythropoietin • Producing renin • Converting vitamin D into its active form

  10. Excretionof Metabolic Waste Products • Urea (from protein metabolism) • Uric acid (from nucleic acid metabolism) • Creatinine (from muscle metabolism) • Bilirubin (from hemoglobin metabolism) • Metabolites of various hormones

  11. Excretionof Foreign Chemicals • Pesticides • Food additives • Toxins • Drugs

  12. Regulation of Water and Electrolyte Balances • Water • Sodium • Potassium • Hydrogen Ions • Calcium, Phosphate, Magnesium, etc..

  13. Regulation of Acid-Base Balance Kidneys Excrete acids (kidneys are the only means of excreting non-volatile acids, such as sulfuric acid and phosphoric acid. Regulate body fluid buffers ( e.g. Bicarbonate)

  14. Regulation and production of hormones and enzymes • The kidney produces: • Erythropoietin • 1,25 dihydroxycholecalciferol (Vitamin D3, calcitriol) • Renin • Vasoactive Agents

  15. Regulation of Erythrocyte Production Hypoxia Erythropoietin O2 Delivery Kidney Erythrocyte Production in Bone Marrow Kidneys produce Erythropoietin: a hormone that stimulates bone marrow to produce red cells.

  16. Regulation of Vitamin D Activity • Kidney produces 1,25- dihydroxycholecalciferol • The active form of vitamin D that important in calcium and phosphate metabolism.

  17. Renin production • It is an enzyme secreted by the kidneys from granular cells of the juxtaglomerular apparatus. • It activates the renin-angiotensin system by converting angiotensinogen to angiotensin I.

  18. Vasoactive Agents • Regulate the capacity of the vasculature • Endothelin • Thromboxanes • Prostaglandins • Nitric oxide • Natriuretic peptides

  19. Metabolism of Hormones Most peptide hormones are metabolized and excreted by the kidney (e.g., insulin, angiotensin II, etc.)

  20. Regulation of Arterial Pressure • Control of Extracellular Fluid Volume by excreting variable amounts of sodium and water. • Endocrine Organ secreting vasoactive factors or substances • Angiotensin II • Prostaglandins

  21. GLOMERULAR FILTERATION

  22. Glomerular filtration Tubular reabsorption Tubular secretion Urine results from these three processes. Basic Renal Processes Excretion = Filtration – Reabsorption + Secretion

  23. Composition of the Glomerular Filtrate • It is the fluid within the Bowman’s capsule that is essentially cell-free and protein-free and contains crystalloids in virtually the same concentrations as in the plasma. • It is free from: • Blood cells • Protein • Protein-bound molecules (calcium, fatty aids, amino acids)

  24. Glomerular Capillary Filtration Barrier • Endothelium (fenestrated) • Basement Membrane negatively charged, restriction site for proteins • Epithelial Cells, restriction site for proteins. Characterized by foot-like processes (podocytes).

  25. Glomerular Filtration Rate (GFR) GFR: The volume of plasma filtered from both kidneys per minute. GFR = 125 ml/min = 180 liters/day Plasma volume is filtered 60 times per day GFR= Filtration Coefficient (Kf) x Net Filtration Pressure(NFP)

  26. Factors Affecting GFR Filtration Coefficient (Kf) Net Filtration Pressure(NFP)

  27. Filtration coefficient • Filtration coefficient (Kf): A measure of the product of the hydraulic conductivity (water permeability)and filtering surface area of the capillaries. • glomerular capillary filtration coefficient = 12.5 ml/min per mmHg, or 4.2 ml/min per mmHg/ 100gm • (400 x greater than in tissues such a muscle)

  28. Increased Glomerular Capillary Filtration Coefficient (Kf) Increases GFR • Normally not highly variable • Kf reduces by reducing the number of functional glomerulus(decrease surface area) or by increasing the thickness BM (reducing its hydraulic conductivity). • Diseases that can reduce Kf and eventually GFR • Chronic hypertension • Diabetes mellitus • Glomerulonephritis

  29. Forces determining Net Filtration Pressure (NFP) • Three physical forces involved • Glomerular capillary blood hydrostatic pressure • Plasma-colloid osmotic osmotic pressure • Bowman’s capsule hydrostatic hydrostatic pressure

  30. 1 1 1 GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg 2 2 CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg 3 BLOOD COLLOID OSMOTIC PRESSURE (BCOP) = 30 mmHg Afferent arteriole Afferent arteriole Afferent arteriole Proximal convoluted tubule Proximal convoluted tubule Proximal convoluted tubule Efferent arteriole Efferent arteriole Efferent arteriole NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg Glomerular (Bowman's) capsule Glomerular (Bowman's) capsule Glomerular (Bowman's) capsule Capsular space Capsular space Capsular space

  31. Calculation of Glomerular Filtration Rate (GFR) • GFR = Filtration Coefficient (Kf ) x Net Filtration Pressure (NFP) • GFR = 12.5 x 10 = 125 ml/min= 180 liters/day • GFR in females is less (110 ml/min)

  32. Tubular Reabsorption & Secretion

  33. Urinary excretion = Glomerular filtration - Tubular reabsorption + Tubular secretion WHERE & HOW

  34. Tubular reabsorption • Reabsorption – return of most of the filtered water and many solutes to the bloodstream • About 99% of filtered water reabsorbed • PCT cells- largest contribution • Both active and passive processes • Reabsorbed substances carried by the peritubular capillaries to the venous system. • Tubular reabsorption is highly selective (unlike filtration).

  35. Tubular Secretion • Tubular secretion is important for: • Eliminates urea and uric acid • Ridding the body of excess potassium ions • Controlling blood pH by secreting H+

  36. Sodium Balance • Na+ is major cation in ECF Amount of sodium in ECF Volume of ECF Plasma volume Blood volume Blood pressure

  37. OVERALL HANDLING OF NA+

  38. Potassium handling by nephron

  39. Potassium balance • Acid base abnormalities: • ICF has considerable buffering capacity for H+ • H+- K+ exchange • Alkalosis hypokalemia • Acidosis hyperkalemia • acid base disturbances often associated with K+ disturbances with the exception of • Respiratory acidosis & alkalosis • Acidosis caused by organic acids (lactic acid,ketoacids)

  40. Renal Failure

  41. CLASSIFICATION • TWO TYPES • Acute and chronic ACUTE RENAL FAILURE (ARF) 1) onset—1-2 days 2) Rapid decline in renal functions 3) Azotemia—increase in urea, nitrogen, uric acid and creatinine. BUN - 10 to 20 mg/dl. UREA - 15 to 40 mg/dl. Creatinine - 0.5 to 1.5 mg/dl. 4) Decrease in GFR

  42. TYPES OF ARF • PRE-RENAL • INTRINSIC OR INTRA-RENAL • POST RENAL

  43. PRE-RENAL ARF CAUSES 1) HYPOVOLEMIA Hemorrhage Dehydration Loss of GI fluids Burns

  44. 2) Decreased vascular filling Anaphylactic shock septic shock Vasoactive agents Drugs Radiocontrast agents 3) Heart failure

  45. INTRINSIC OR INTRARENAL ARF • ACUTE TUBULAR NECROSIS-ATN CAUSES 1) Renal ischemia 2) Nephrotoxic agents—aminoglycosides, gentamicin, chemo-cisplatin, ifosfamide. 3) Heavy metals 4) Intra-tubular obstruction—Hb, Mg, Myeloma, light chains. ACUTE RENAL DISEASE—glomerulonephritis and pyelonephritis.

  46. POST-RENAL ARF • Bilateral ureteric obstructions • Bladder outlet obstructions • BPH • Urethtral malignancies, stone.

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