RENAL PHYSIOLOGY, HOMEOSTASIS OF FLUID COMPARTMENTS (1) Dr. Attila Nagy 2017 Functional role of the kidney 1.Homeostasis of fluid compartments (isosmia, isovolemia, isoionia, isohydria,) 2. Elimination of non-required substances 2.1. endogenous (metabolic end-products), 2.2. exogenous (organic and anorganic substances) 3. Endocrine function (erythropoetin, renin, calcitriol) 4. (gluconeogenesis) 1
Functional anatomy of the kidney Position, capsule, cortex and medulla, pyramids, calyx, pyelon. 2
The functional unit of the kidney is the nephron. One kidney contains 1.2 million nephrons. Components of the nephron : 1/. A Malpighi body (glomerulus + Bowman-capsule) 2/. Proximal nephron 2.1. convoluted tubule 2.2. descending segment 3/. Loop of Henle (thin descending segment, thin ascending segment, thick ascending segment) 4/. Distal nephron (distal convoluted tubule and collecting duct 3
Cortical and juxtamedullary nephrons 1. The position of the glomerulus 2. The length of the Henle-loop, long-looped nephrons, (juxtamedullary) short-looped nephrons (cortical) Filtration 180 l/day Adjusting (rough) large quantities Concentration Adjusting (fine) Urine 1.5 l/day 4
(Learning objectives: 52, 53) Blood supply: renal artery, lobar artery, interlobar artery, arcuate artery, interlobular aa, afferent arteriole, glomerular capillaries, efferent arteriole, vasa recta, peritubular capillaries, 5
Renal functions 1. Glomerular filtration 2. Tubular functions (reabsorption and secretion) Glomerulus vas efferens 6
JUXTAGLOMERULAR APPARATUS (JGA) endfeet of podocytes mesangial cell capillary podocyte mesangial cell Glomerular Filtration (180 l/day) GFR=Glomelural Filtration Rate (135 ml/min) Factors determining filtration 1. properties of glomerular membrane (extension, permeability) 2. effective filtration pressure 3. properties of filtrating substances 7
ad. 1 Structure of the glomerular membrane 1. capillary endothel, 2. basal membrane, 3. epithel cells (podocytes) Permeability of glomerular membrane 1. pores between fenestrated endothel cells (50-100 nm) 2. pores between podocytes (25 nm). 3. hydrated collagen and protoglycane channels of the basal membrane (3-5 nm) 8
Pressure relationship in the kidney vessels hydrostatic pressure 9
ad. 2. Effective filtration pressure (P eff) Starling-principle: P eff = (P C - P B ) - (π C - π B ) P = hydrostatic pressure P C = glomerular capillary pressure P B = pressure in Bowman-capsule π = oncotic pressure π C = oncotic pressure in glomerular capillary π B = oncotic pressure in Bowman-capsule 10
GFR = K f P eff Peff= (P C - P B ) - (π C - π B ) GFR= Kf[(P C - P B ) - (π C - π B )] K f = filtration coefficient P eff = effective filtration pressure GFR = K f [P C - P B - π c ] GFR = Kf [55Hgmm 15Hgmm -30 Hgmm] 11
ad. 3. Properties of filtrating substances Molecular weight Molecular shape, Electrostatic factors The glomerular filtrate is protein-free and lipid-free plasma Substance Molecular Molecular sizes Filterability weight filtrate/plasma radius diameter concentration ratio Water 18 0.10 1.0 Urea 60 0.16 1.0 Glucose 180 0.36 1.0 Sacharose 342 0.44 1.0 Inulin 5500 1.48 0.98 Myoglobin 1600 1.95 5.4 0.75 Egg albumin 43500 2.85 8.8 0.22 Hemoglobin 64500 3.25 5.4 15.0 Albumin 69000 3.55 0.03 0.01 12
Relative filterability Polykationic dextrane Polyanionic dextrane Neutral dextrane Effective molecular radius 13
Glomerular Filtration (180 l/day) GFR=Glomelural Filtration Rate (100-130 ml/min) Inulin clearance (120-130 ml/min) Kreatimin clearance (90-150 ml/min) Clearance-principle Clearance is the amount of plasma that is cleared of a substance during one minute (or one sec). It is a virtual plasma volume characteristic to a substance in question. C = U x V P 14
Significance of Clearance: Characterization of kidney function. Estimation of characteristic parameters of the kidney. Characterization of the fate of particular substances in the kidney. 15
Estimation of GFR 16
Normal values RPF: 660 ml/min (480-800 ml/min) RBF: 1300 ml/min (870-1540 ml/min) Glomerular Filtration Rate (GFR): 100-130 ml/min Filtration Fraction (FF= GFR/RPF): ~ 0.2 Urinproduction: 650-3500 ml/day, 0.5-20 ml/min Osmolality of the urin: 70-1200 mosm/l ph of the urin: 4.0-8.0 Specific weight of the urin: 1.001-1.038 (1.015-1.025) Regulation of renal circulation Renal autoregulation: RBF and GFR is fairly constant between arterial pressure values of 80-180 Hgmm - Bayliss-effect - Local vasoactive metabolites - Tubuloglomerular feedback 17
Relationship between arterial pressure and urine production Pressure diuresis 18
Neural regulation of renal circulation Sympathetic nerve Pressor response Renorenal reflex 19