1. Renal Physiology and Function Ricki Otten MT(ASCP)SC uotten@unmc.edu

2. 2 Objectives: Please review the objectives located on page 1 of the lecture handout

3. 3 Kidney Function Form urine (excretory function) Maintain acid-base balance Regulates body water balance Maintain electrolyte balance Aids in maintaining BP Excrete toxic (and) waste products Reabsorb essential substances Hormonal function: –Target organ for aldosterone, ADH –Secretes renin (an enzyme) –Erythropoietin, vitamin D

4. 4 Kidney Function Depends upon proper –Renal blood flow (20-25% cardiac output) –Glomerular filtration –Tubular absorption –Tubular secretion

5. 5 Urinary System Each kidney about the size of your fist

6. 6 Inflammation/Infection Pyelonephritis Cystitis Urethritis

7. 7 Nephron Functional unit of kidney ~1.5 million per kidney Components –Glomerulus –Tubules (PCT, Loop of Henle, DCT) –Collecting ducts/tubules Functions to form urine –Filtration –Reabsorption –Secretion

8. 8 Glomerulus ‘Capillary tuft’ Bowman’s space Bowman’s Capsule Afferent arteriole Efferent arteriole Empties into PCT

9. 9 Glomerulus Function: Filtration of blood –Allows passage of water, electrolytes and low molecular weight substances (<70,000) –Filtration based on solute’s size and charge Difference between glomerular filtrate and blood is absence of –Protein –Protein-bound substances: bilirubin, drugs –Cells (RBC, WBC)

10. 10 Glomerular Filtrate: Specific Gravity: 1.010 Ultrafiltrate volume: 120 ml/min

11. 11 Glomerular Filtration Dependent upon –Basement membrane cell structure –Hydrostatic pressure –Oncotic pressure –RAA system

12. 12 Glomerular Filtration Dependent upon –Basement membrane cell structure –Hydrostatic pressure –Oncotic pressure –RAA system

13. 13 Renin-Angiotensin-Aldosterone

14. 14 Renal Tubules PCT Loop of Henle –Descending limb –Ascending limb Not permeable to water DCT –ADH (controls water) –Aldosterone (controls Na+) Collecting ducts/tubules –ADH (controls water)

15. 15 Renal Tubules Functions –Reabsorption of essential substances –Secretion of waste, toxins, metabolites, drugs, protein-bound substances, etc Final urine output: 1 ml/min Range: 0.3 – 15 ml/min (dependent on hydration status)

16. 16 Tubular Transport Mechanisms Active transport: energy is required Passive transport: simple diffusion Renal Threshold –Glucose: 160-180 mg/dl (plasma)

17. 17

18. 18 Normal Urine Composition Water: 94% Solutes: 6% –Urea –Sodium –Chloride

19. 19 Normal Urine Composition Water: 94% Solutes: 6% –Urea –Sodium –Chloride Urea: end product of protein metabolism Creatinine: end product of muscle metabolism Uric acid: end product of purine metabolism

20. 20 Factors Influencing Concentration of Substances Dietary intake Physical activity Body metabolism Endocrine function (ADH, Aldosterone) Body position (orthostatic proteinuria)

21. 21 Urine Output Average 24 hour volume: –Normal: 1500 – 2000 ml/24 hour –‘Extreme’: 600 – 2500 ml/24 hours Factors that influence urine output (volume) –Fluid intake –Non-renal loss (vomiting, diarrhea, sweating) –Secretion of ADH (too little, too much) –Body’s need to excrete solutes (glucose)

22. 22 Abnormal Urine Output Polyuria: >2500 ml/24 hr –Artificially induced by suppression of ADH (diuretics, caffeine, alcohol) –Diabetes mellitus: plasma glucose exceeds renal threshold –Diabetes insipidus: Neurogenic DI: lack of ADH Nephrogenic DI: tubules unable to respond to ADH

23. 23 Abnormal Urine Output Oliguria (low) Anuria (absence) Nocturia

24. 24 Renal Function Tests Tubular Reabsorption Glomerular Filtration Renal Blood Flow Tubular Secretion

25. 25 Tubular Reabsorption Tests Can the kidneys concentrate urine “Concentration Tests”: control of fluid intake important in interpretation of test –Fluid deprivation –Free water clearance

26. 26 Tubular Reabsorption Tests Laboratory: –Specific gravity (number and density) Refractometer Reagent strip –Osmolality (number of particles in solution) Better test More accurate

27. 27 Glomerular Filtration Tests Assess filtering ability of glomerulus “Clearance tests” –Measures the RATE at which kidneys can clear a ‘filterable’ substance from the blood –This substance must not be reabsorbed or secreted by the tubules –GFR = glomerular filtration rate

28. 28 Glomerular Filtration Tests Specimen requirements –Timed urine specimen: 24 hour collection –Plasma sample Clearance calculation: UV = ml/min P

29. 29 Glomerular Filtration Tests Endogenous –Creatinine (most common) Exogenous –Inulin (considered the ‘standard’)

30. 30 Glomerular Filtration Tests Creatinine clearance test –Endogenous substance (found in the body) –Produced at a steady rate –Dependent on muscle mass (male, female, child, adult) –Thus ‘normalized’ to body surface area using a nomogram Children Obese

31. 31 Glomerular Filtration Tests Calculate creatinine clearance: UV P Urine creatinine (U)185 mg/dl Plasma creatinine (P) 0.9 mg/dl Urine volume (V) 1250 ml/24 hr Height 6’0” Weight260 lb

32. 32 Calculate Creatinine Clearance CrCl = UV P

33. 33 Calculate Creatinine Clearance UV = 185 mg/dl x 1250 ml x 1 hour = 178.4 = P 0.9 mg/dl 24 hours 60 min CrCl = 178 ml/min

34. 34 Calculate Creatinine Clearance UV = 185 mg/dl x 1250 ml x 1 hour = 178.4 = P 0.9 mg/dl 24 hours 60 min CrCl = 178 ml/min Is this normal for a 20 year old male?

35. 35 Calculate Creatinine Clearance UV = 185 mg/dl x 1250 ml x 1 hour = 178.4 = P 0.9 mg/dl 24 hours 60 min CrCl = 178 ml/min Is this normal for a 20 year old male? No, it is increased Correct value for body surface area

36. 36 Corrected Creatinine Clearance CrCl = 178 ml/min Corrected CrCl = CrCl x 1.73m2 = 178 ml/min x 1.73 BSA 2.39 = 128.8 = 129 ml/min

37. 37 Corrected Creatinine Clearance CrCl = 178 ml/min Corrected CrCl = 129 ml/min Is this normal for a 20 year old male?

38. 38 Corrected Creatinine Clearance CrCl = 178 ml/min Corrected CrCl = 129 ml/min Is this normal for a 20 year old male? Yes

39. 39 Renal Reserve Large margin of reserve in renal function Greater than 50% of kidney function must be lost before –Clinical symptoms apparent –Biochemical abnormalities evident Thus, not useful for screening for early renal disease

40. 40 Renal Blood Flow Tubular Secretion No objectives

41. 41