2. RENAL PHYSIOLOGY DR SYED SHAHID HABIB MBBS DSDM FCPS Associate Professor Dept. of Physiology College of Medicine & KKUH

3. 1) Introduction 2)Glomerular Filtration 3)Tubular Processing 4)Urine Concentrating Mechanism 5)Micturition Renal Physiology

4. PHYSIOLOGIC ANATOMY OF KIDNEYS Size Clenched Fist Weight 150 grams

5. FUNCTIONS OF THE KIDNEY 1.Regulation of water (extracellular fluid volume) 2.Maintenance of electrolyte balance (Na +, K +, HCO 3 -, Ca ++ ) 3.Regulation of arterial pressure 4.Regulation of blood pH

6. FUNCTIONS OF THE KIDNEY (Cont.) 5.Excretion of wastes (creatinine, urea, benzoate, penicillin, saccharin) 6.Secretion, metabolism, and excretion of hormones Hormone production (Erythropoietin, Renin) Activation of Vitmain D 7.Gluconeogenesis

7. PHYSIOLOGIC ANATOMY OF KIDNEYS

8. FUNCTIONAL UNIT OF THE KIDNEY CONSISTS OF: –BLOOD VESSELS: –URINARY TUBULES: BOWMAN’S CAPSULE PROXIMAL CONVOLUTED TUBULE LOUP OF HENLE DISTAL CONVOLUTED TUBULE COLLECTING DUCT NEPHRON

9. PARTS OF NEPHRON

10. NEPHRON TYPES Superficial (cortical) [85 %] o Capable of forming dilute urine Juxtamedullary [15 %] o Capable of forming concentrated (> 300 mOsm/kg) urine

11. 1-2 % Blood Flows Through Juxta Medullary Nephrons NEPHRON TYPES Cortical and Juxtamedullary Nephrons Originates in outer 2/3 of cortex. Originates in inner 1/3 of cortex.

12. Renal blood flow About 21% of cardiac output Renal circulation is characterized by: 1.High rate of blood flow. 2.Presence of two capillary beds: a. glomerular : they filter large amounts of fluid and solutes. b. peritubular capillaries: absorption of most of filtered fluid.

13. RENAL BLOOD VESSELS AFFERENT ARTERIOLE: –DELIVERS BLOOD INTO THE GLOMERULI. GLOMERULI: –CAPILLARY NETWORK THAT PRODUCES FILTRATE THAT ENTERS THE URINARY TUBULES. EFFERENT ARTERIOLE: –DELIVERS BLOOD FROM GLOMERULI TO PERITUBULAR CAPILLARIES. PERITUBULAR CAPILLARIES: –VASA RECTA.

14. BOWMAN’S CAPSULE

15. 4 RENAL PROCESSES 1. Filtration 2. Reabsorption 3. Secretion 4. Excretion 1. Filtration 2. Reabsorption 3. Secretion 4. Excretion Urinary Excretion Rate = Filtration Rate – Reabsorption Rate + Secretion Rate

16. Renal Corpuscle Glomerular filtrate collects in capsular space, flows into renal tubule

17. FILTRATION MEMBRANE 1. Endothelium 3. Podocyte Endothelium of Glomerular Capillaries 4-8 nm size particles can be filtered easily 2. Basement Membrane Filtration

18. Glomerular membrane 1. endothelium of glomerular capillaries (Fenestra) 2. Basement membrane prevent passage of molecules of molecular weight more than 70,000) (- ve charge) (albumin and larger are held back, so normally no protein in urine). 3. Podocytes secrete (slit pores)

19. Glomerular membrane

20. RENAL PHYSIOLOGY GLOMERULAR FILTRATION

21. FILTRATION AND OSMOSIS At a molecular level, filtration is the bulk flow of fluid through a membrane or other barrier that selectively impedes the movement of some molecules, the largest being impeded most. This process is sometimes called ULTRAFILTRATION.

22. GLOMERULAR FILTRATE GLOMERULAR FILTRATE CONTAINS ALL CONSTITUENTS OF PLASMA IN SAME CONCENTRATION EXCEPT BLOOD CELLS AND PLASMA PROTEINS

23. Renal blood flow Normal renal blood flow = 1200 ml/min ….1/5 th cardiac output.

24. GFR=125ML/MIN OR 125X60X24=180000=180L/DAY Normal Urinary Output=1.5 L/day Daily Reabsorption 180-1.5=178.5 L/day Percent Reabsorbed = 178.5x100/180=99.2% Percent Excreted = 100-99.2=0.8% (Less than 1 % becomes urine) Obligatory Urinary Output=0.5- 0.6L

25. Glomerular Filtration Rate (GFR) Defined as: The volume of filtrate produced by both kidneys per min –Averages 125 ml/min –Totals about 180L/day (45 gallons) 99% of filtrate reabsorbed, 1 to 2 L urine excreted or death would occur from water lost through urination GFR = NFP x K f  125 ml/min or 180 L/day GFR = 10 X 12.5 = 125 ml/min 17-24

26. Forces controlling GFR &Net Filtration Pressure (NFP)

27. Forces Favoring Filtration (mm Hg) Glomerular hydrostatic pressure 60 Forces Opposing Filtration (mm Hg) Bowman's capsule hydrostatic pressure 18 Glomerular capillary colloid osmotic pressure 32 Net Filtration Pressure = 60 – (18 + 32) = +10 mm Hg DETERMINANTS OF GFR

28. CONTROL OF GFR GFR = Kf x [(P G -P B )-(  G -  B )] GFR = Kf x [(60-18)-(32- 0)] (1)Hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure, PG), which promotes filtration (2)The hydrostatic pressure in bowman's capsule (PB) outside the capillaries, which opposes filtration (3)The colloid osmotic pressure of the glomerular capillary plasma proteins (πg), which opposes filtration (4)The colloid osmotic pressure of the proteins in bowman's capsule (πb), which promotes filtration

29. Forces determining GFR Increased Bowman’s capsule pressure decreases GFR. It can happen in urinary obstruction e.g. stones, tumors.. Increased glomerular capillary colloid osmotic pressure decreases GFR. Increased glomerular capillary hydrostatic pressure increases GFR. This pressure is affected by: -ABP. -Afferent arteriolar resistance. -Efferent arteriolar resistance

30. Physiological control of GFR GFR controlled by adjusting glomerular hydrostatic pr and glomerular capillary colloid osmotic pr –Sympathetic control –Hormonal mechanism: renin and angiotensin –Intrinsic factors (autoregulation)

31. Sympathetic Control of GFR When the sympathetic nervous system is at rest: –Renal blood vessels are maximally dilated Under stress: –Norepinephrine is released by the sympathetic nervous system –Epinephrine is released by the adrenal medulla –Afferent arterioles constrict and filtration is inhibited---  ↓ P G  GFR ↓

32. GFR remains constant over a large range of values of BP 75-160 mmHg AUTOREGULATION OF GFR

33. Autoregulation 1.Myogenic 2.Tubuloglomerular Feedback (juxtaglomerular apparatus)

34. Juxtaglomerular Apparatus - vasomotion - monitor salinity

35. Hormonal Control of GFR -efferent arterioles

36. Effects of Angiotensin II

37. Physical Determinants*Physiologic/Pathophysiologic Causes ↓ K f → ↓ GFRRenal disease, diabetes mellitus, hypertension ↑ P B → ↓ GFRUrinary tract obstruction (e.g., kidney stones) ↑ π G → ↓ GFR↓ Renal blood flow, increased plasma proteins ↓ P G → ↓ GFR ↓ A P → ↓ P G ↓ Arterial pressure (has only small effect due to autoregulation) ↓ R E → ↓ P G ↓ Angiotensin II (drugs that block angiotensin II formation) ↑ R A → ↓ P G ↑ Sympathetic activity, vasoconstrictor hormones (e.g., norepinephrine, endothelin) * Opposite changes in the determinants usually increase GFR. Kf, glomerular filtration coefficient; PB, Bowman's capsule hydrostatic pressure; πG, glomerular capillary colloid osmotic pressure; PG, glomerular capillary hydrostatic pressure; AP, systemic arterial pressure; RE, efferent arteriolar resistance; RA, afferent arteriolar resistance.

38. Measurement of GFR Creatinine clearance Inulin clearance Clearance (ml/min)=( U* x V*)/P*

39. Urinary Excretion Rate = Filtration Rate – Reabsorption Rate + Secretion Rate inulin urea glucCreat