Brief overview of mammalian renal physiology Jason Williams University of Nevada Las Vegas 2-28-07 1 2 Outline for renal physiology lecture I. Specific functions of the kidney II. Kidney structure III. Nephron: the functional unit of the kidney IV. Basic renal process V. Specific renal process VI. How does the kidney create hyperosmotic urine? VII. Renal regulation of sodium, water, and potassium VIII. Hydrogen ion regulation IX. Diuretics and kidney disease 3 What does the kidney do? Kidneys filter plasma to regulate the makeup of the interstitial fluid and blood. 4 What is interstitial fluid? 5 Where is Interstitial fluid located? 6 I. Specific Functions of the Kidney: 1. Form urine: (95% water, 5% solutes) A. Removal of metabolic waste from plasma i. urea (protein breakdown) ii. uric acid (nucleic acid breakdown) - insoluble in blood - can precipitate out in blood and cause gout iii. creatinine (muscular creatine phosphate breakdown) 7 B. Removal of foreign compounds - drugs, food additives, pesticides 8 C. maintain water, inorganic ion concentrations i. important for proper fluid volume 9 2. Other Functions of the kidney A. Acts as endocrine gland i. erythropoietin ii. Renin iii. 1,25 dihydroxyvitamin D3 B. Gluconeogenesis – during times of fasting i. amino acids → glucose 10 II. Structure of the Kidney: 1. Location: - retroperitoneal - superior lumbar region - twelfth thoracic to the third lumbar vertebrae 11 2. Part of the urinary system - ureters - bladder - urethra 12 3. External anatomy of the kidney - Bean shaped - vertical cleft called the renal hilus - Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilus 13 4. Internal anatomy of a kidney: The kidney has three main regions: A. Renal Cortex - outer region (granular) B. Renal Medulla - inner region (striated) - consists of a number of triangular structures called renal pyramids C. Renal pelvis - major calyces 14 III. Nephron: The functional unit of the kidney i. smallest unit capable of forming urine ii. microscopic, each kidney has about 1 million 15 1. The nephron consists of two distinct regions: A. Renal corpuscle B. Tubule 16 A. Anatomy of the renal corpuscle: i. Glomerulus - Afferent and efferent arterioles ii. Bowman’s capsule - Bowman’s space 17 B. Anatomy of the tubule: i. Very narrow hollow tube of single celled epithelial tissue. ii. Contiguous with Bowman’s capsule 18 C. Tubule consists of: 1. Proximal tubule (convoluted and straight) 2. Loop of Henle (descending and ascending) 3. Distal convoluted tubule 4. Connecting tubule 5. Collecting duct 19 D. Vascularization of the nephron Two sets of capillaries: a. Glomerulus b. Peritubular capillaries Connected by efferent arteriole 20 IV. Basic renal process 1. Urine formation: A. begins with glomerular filtration ends with urine formation. 21 B. glomerular filtrate has essentially the same concentrations of solutes as blood plasma, minus proteins 22 B. Glomerular filtrate ≠ Urine Substance Amount Filtered per day Amount excreted per day Water, L 180 1.8 Sodium, g 630 3.2 Glucose, g 180 0 Urea, g 54 30 23 C. How is glomerular filtrate altered as it moves through the tubule? -Tubular reabsorption -Tubular secretion Excreted = filtered - reabsorbed + secreted 24 B. Glomerular filtrate ≠ Urine Substance Amount Filtered per day Amount excreted per day Water, L 180 1.8 Urea, g 54 30 Penicillin 3 10 Creatinine, g 20 ~20 25 V. Closer look at renal processes 1. glomerular filtration - glomerular filtrate has essentially the same concentrations of solutes as blood plasma, minus proteins 26 A. Glomerular filtrate passes through three layers i. Single-celled capillary endothelium ↓ ii. Non-cellular proteinaceous layer of basement membrane. ↓ iii. Single-celled epithelium lining (podocytes) 27 B. Forces involved in filtration Net glomerular filtration pressure= PGC-PBS-πGC 55 - 15 - 30 = 10mmHG 28 C. Glomerular Filtration Rate (GFR) GFR = the volume of fluid/plasma filtered from the glomeruli to the Bowman’s space per unit time. GFR = 180 L/day for average adult blood volume filtered ~60 times per day GFR is under physiological regulation 29 2. Clinical determination of GFR 30 A. Introduction: i. Estimated glomerular filtration rate by measuring inulin and creatinine clearance. ii. Why?: Abnormal GFR may suggest renal disease (the leading cause of death in captive cheetahs) 31 B. Brief Materials and Methods: i. measure of GFR 1. injected cats with known amount of inulin Inulin: - foreign polysaccharide - fully filtered - not reabsorbed 32 B. Brief Materials and Methods: (Cont.) 2. Determine amount of inulin in serum and urine sample 3. Calculate GFR in milliliters: (Urine conc. of inulin) X (urine volume) (serum conc. of inulin) 4. Report final GFR as: ml min-1 kg-1 33 C. Results: Ccr = creatinine clearance rate - Creatinine produced endogenously - typically only filtered - measured in same fashion as inulin GFR 34 D. Conclusions: 35 Tubular Reabsorption: 36 3. Reabsorption A. Occurs in: proximal tubule and loop of Henle 37 B. General process: i. Luminal membrane → basolateral membrane → interstitial fluid → peritubular capillary ii. Tight junction → interstitial fluid → peritubular capillary 38 C. Tubular reabsorption occurs by: i. Diffusion – water, urea, other lipid soluble substances ii. Mediated transport – Move substances “uphill” against diffusion gradient. (glucose, amino acids, etc.) 39 40 D. Efficiency of tubular reabsorption: Substance Amount Amount Percent Filtered excreted reabsorbed per day per day Water, L 180 1.8 99.0 Sodium, g 630 3.2 99.5 Glucose, g 180 0 100 Urea, g 54 30 44 Rates of reabsorption are under physiological control 41 Tubular Secretion 42 4. Tubular Secretion A. Moves substances from: - peritubular capillary → tubular lumen B. occurs by diffusion or mediated transport C. secreted substances: hydrogen ions, potassium, foreign chemicals, choline etc. 43 5. Division of Labor in Nephron: A. Renal corpuscle = filtrate B. Proximal tubule = primary reabsorption C. Proximal tubule = primary secretion 44 D. Renal D. Loop of Henle = reabsorption E. Distal segments = fine tuning, under homeostatic control 45