1. Ann Bugeja, MD FRCPC Integrative Lecture Week 1

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3. Objectives No new objectives

4. Anatomy and Renal Physiology

5. The Kidneys Retroperitoneal Each kidney contains 400,000 - 2 million nephrons (usually 1 million/kidney) Fixed number of nephrons at birth Nephrons mature during the first 2 years of life Senescence begins at age 60

6. The nephron 2 parts: –Glomerulus –Tubules The distal portions of different nephrons join together to form the collecting system and ultimately renal pelvis

7. Glomerulus Click View then Header and Footer to change this footer

8. Glomerular basement membrane 3 components of GBM to make up filtration barrier: –Endothelium –Collagenous Membrane –Podocytes This combination allows the passage of water and small MW molecules (such as Na, K), amino acids, but retains the blood cells, albumin, etc.

9. GBM

10. Tubules Click View then Header and Footer to change this footer

11. Function of nephrons 1.Filtration The filtration of blood plasma that passes through the glomerular capillaries 2.Reabsorption It is the movement of a substance (liquid) from the tubular lumen to peritubular capillaries. This movement can be passive or active. 3.Secretion It is the movement of a substance (liquid) from the peritubular capillaries (bypassed filtration) to the tubular lumen. This movement can be passive or active.

12. Evaluation of Renal Function

13. Testing The majority of kidney diseases are diagnosed USING simple analysis: –Blood: creatinine, electrolytes, hemoglobin, etc. –Urine: analysis of urine by dipstick and microscopy –Radiology: Ultrasound In some cases we need to more specific tests, such as renal biopsy These topics will be further discussed over the coming weeks

14. Urinalysis The complete urinalysis includes: –Appearance –Chemical analysis (dipstick) –Microscopy

15. Urinalysis - dipstick pH Protein (albumin) Blood Specific gravity Glucose Ketones Nitrites (infection) Leukocytes (infection, inflammation)

16. Urinalysis - microscopy Cells –RBC (red cells) 0-5/HPF normal (depends on your laboratory) –WBC (white cells) Infection or inflammation –Epithelial cells (tubules) Can be normal,but they are also seen in acute tubular necrosis & other tubulointerstitial diseases –Other cells Squamous cells (vagina) Transitional epithelial cells (bladder, ureters)

17. Glomerular Filtration and GFR

19. Glomerular Filtration ForcesmmHg Favouring filtration: Glomerular capillary pressure 50 Opposing filtration: Hydrostatic pressure in Bowman’s space -10 Osmotic Gradient-30 Net filtration pressure10

20. Clinical GFR The body produces muscle creatinine (enzymatic dephosphorylation of phospho-creatinine) Creatinine is present in plasma and freely filtered, not reabsorbed, but slightly secreted by the proximal tubule CrCl (GFR) = (V U x U cr ) / S cr

21. Relationship between GFR & creatinine

22. GFR in practice To measure creatinine clearance, we need a collection of urine for 24 hr: Is not always accurate Difficult to do correctly Is not very practical Other method? Estimate GFR from serum creatinine! How?

23. GFR - equation Cockcroft and Gault Formula: GFR = (140-age) x kg x 1.2 (x 0.85 for women) Creatinine (µmol/l) Memorize this! Need to be in steady state!

24. GFR - equation MDRD GFR (in mL/min per 1.73 m 2 ) = 170 x (P Cr [mg/dL]) -0.999 x Age -0.176 x (S urea [mg/dL]) -0.170 x (Albumin [g/dL]) +0.318 –The value obtained must be multiplied by 0.762 if the patient is female or by 1.180 if the patient is black Do not need to calculate on exam.

25. Systolic blood pressure 100180 Flow rate GFR Renal blood flow Autoregulation of GFR Following an increase or decrease in blood pressure autoregulatory mechanisms prevent large variations in GFR

26. JGA

27. The urinary system

28. Fowler et al. 2008:9;453.

29. Questions Click View then Header and Footer to change this footer