Nephron: functional unit of the kidney Figure 26-3; Guyton and Hall 1

Nephron Tubular Segments Figure 26-4; Guyton and Hall 2

Structure of the juxtaglomerular apparatus: macula densa Figure 26-17; Guyton and Hall 3

Cortical and Juxtamedullary Nephron Segments Figure 26-5; Guyton and Hall 4

http://www.youtube.com/watch?v=glu0dzK4dbU 5

Summary of Kidney Functions Excretion of metabolic waste products: urea, creatinine, bilirubin, hydrogen Excretion of foreign chemicals: drugs, toxins, pesticides, food additives Secretion, metabolism, and excretion of hormones renal erythropoetic factor 1,25 dihydroxycholecalciferol (Vitamin D) Renin Regulation of acid-base balance Gluconeogenesis: glucose synthesis from amino acids Control of arterial pressure Regulation of water & electrolyte excretion 6

Basic Mechanisms of Urine Formation Figure 26-8; Guyton and Hall 7

Renal Handling of Different Substances Figure 26-9; Guyton and Hall 8

Renal Handling of Water and Solutes Filtration Reabsorption Excretion Water (liters/day) 180 179 1 Sodium (mmol/day) 25,560 25,410 150 Glucose (gm/day) 180 0 180 Creatinine (gm/day) 1.8 1.8 9

Glomerular Capillary Filtration Barrier Figure 26-10; Guyton and Hall 10

The Ability of a Solute to Penetrate the Glomerular Membrane Depends on: Molecular size ( small molecules > filterability) Ionic charge (cations > filterability) 11

Effects of Size and Electrical Charge of Dextran on Filterability by Glomerular Capillaries Figure 26-11; Guyton and Hall 12

Clinical Significance of Proteinuria Early detection of renal disease in at-risk patients hypertension: hypertensive renal disease diabetes: diabetic nephropathy pregnancy: gestational proteinuric hypertension (pre-eclampsia) annual “check-up”: renal disease can be silent Assessment and monitoring of known renal disease “Is the dipstick OK?”: dipstick protein tests are not very sensitive and not accurate: “trace” results can be normal & positives must be confirmed by quantitative laboratory test. 13

Figure 26-12; Guyton and Hall

Glomerular Hydrostatic Pressure (PG) Is the determinant of GFR most subject to physiological control Factors that influence PG arterial pressure (effect is buffered by autoregulation) afferent arteriolar resistance efferent arteriolar resistance

Effect of Afferent and Efferent Arteriolar Constriction on Glomerular Pressure Ra Re PG PG Blood Flow Blood Flow GFR GFR Ra GFR + Renal Blood Flow Re GFR + Renal Blood Flow

Effect of changes in afferent arteriolar or efferent arteriolar resistance Figure 26-14; Guyton and Hall

determined by : FF = GFR / RPF RBF G _ RE GFR PG +

Summary of Determinants of GFR Kf GFR PB GFR G GFR A G FF G PG GFR RA PG RE PG GFR GFR GFR (as long as RE < 3-4 x normal)

Assessing Kidney Function Albumin excretion (microalbuminuria) Plasma concentration of waste products (e.g. BUN, creatinine) Urine specific gravity, urine concentrating ability Imaging methods (e.g. MRI, PET, arteriograms, iv pyelography, ultrasound etc) Isotope renal scans Biopsy Clearance methods (e.g. 24-hr creatinine clearance) etc

Clearance Clearance is a general concept that describes the rate at which substances are removed (cleared) from the plasma.

Clearance Technique Renal clearance of a substance is the volume of plasma completely cleared of a substance per min. Cs x Ps = Us x V Cs = Us x V Ps Where: Cs = clearance of substance S Ps = plasma conc. of substance S Us = urine conc. of substance S V = urine flow rate

Use of Clearance to Measure GFR For a substance that is freely filtered, but not reabsorbed or secreted (inulin, 125 I-iothalamate, ~creatinine), renal clearance is equal to GFR amount filtered = amount excreted GFR x Pin = Uin x V GFR = Pin Uin x V Copyright © 2006 by Elsevier, Inc.

Calculate the GFR from the following data: Pinulin = 1.0 mg / 100ml Uinulin = 125 mg/100 ml Urine flow rate = 1.0 ml/min GFR = Cinulin = Pin Uin x V GFR = 125 x 1.0 1.0 = 125 ml/min

Steady-state relationship between GFR and serum creatinine concentration Figure 27-19; Guyton and Hall

Clearances of Different Substances Substance Clearance (ml/min) inulin 125 glucose 0 sodium 0.9 urea 70 Clearance of inulin (Cin) = GFR if Cx < Cin: indicates reabsorption of x if Cx > Cin: indicates secretion of x Clearance creatinine (Ccreat) ~ 140 (used to estimate GFR)

Control of Glomerular Filtration 1. Sympathetic Nervous System RA + RE GFR + RBF 2. Catecholamines ( norepinephrine) RA + RE GFR + RBF 3. Angiotensin II RE GFR + RBF (prevents a decrease in GFR)

Control of Glomerular Filtration 4. Prostaglandins RA + RE GFR + RBF 5. Endothelial-Derived Nitric Oxide (EDRF) RA + RE GFR + RBF 6. Endothelin RA + RE GFR + RBF

Control of Glomerular Filtration 7. Autoregulation of GFR and Renal Blood Flow Myogenic Mechanism Macula Densa Feedback (tubuloglomerular feedback) Angiotensin II ( contributes to GFR but not RBF autoregulation)

Renal Autoregulation 100 80 120 Renal Artery Pressure (mmHg) Glomerular Filtration Rate Renal Blood Flow 1 2 3 4 5 Time (min) Copyright © 2006 by Elsevier, Inc.

Renal Blood Flow and GFR Autoregulation Figure 26-16; Guyton and Hall

Macula Densa Feedback GFR Distal NaCl Delivery Macula Densa NaCl Reabsorption (macula densa feedback) Afferent Arteriolar Resistance GFR (return toward normal)

Myogenic Mechanism Arterial Pressure Stretch of Blood Vessel Cell Ca++ Permeability Vascular Resistance Blood Flow Intracell. Ca++

Regulation of GFR by Ang II Macula Renin GFR Densa NaCl Blood AngII Pressure Efferent Arteriolar Resistance

Macula densa feedback mechanism for GFR autoregulation Figure 26-18; Guyton and Hall