RENAL PHYSIOLOGY, HOMEOSTASIS OF FLUID COMPARTMENTS (1)

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1 RENAL PHYSIOLOGY, HOMEOSTASIS OF FLUID COMPARTMENTS (1) Dr. Attila Nagy 2017 Functional roles 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, thrombopoetin, renin, calcitriol, urodilatin) 4. Intermediate metabolism (gluconeogenesis) 1

2 Functional anatomy of the kidney Position, capsule, cortex and medulla, pyramids, calyx, pyelon. 2

3 Blood supply: renal artery, lobar artery, interlobar artery, arcuate artery, interlobular aa, afferent arteriole, glomerular capillaries, efferent arteriole, vasa recta, peritubular capillaries, The functional unit of the kidney is the nephron. One kidney contains 1.2 million nephrons. 3

4 Components of the nephron : 1/. A Malpighi body (glomerulus + Bowman-capsule) 2/. Proximal nephron (convoluted tubule, descending segment) 3/. Loop of Henle (thin descending segment, thin ascending segment, thick ascending segment) 4/. Distal nephron (distal convoluted tubule, collecting duct) Filtration 180 l/day Adjusting (rough) large quantities Concentration Adjusting (fine) Urine 1.5 l/day 4

5 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) 5

6 Renal functions 1. Glomerular filtration 2. Tubular functions (reabsorption and secretion) Glomerulus vas efferens 6

7 JUXTAGLOMERULAR APPARATUS (JGA) endfeet of podocytes mesangial cell capillary podocyte mesangial cell Glomerular Filtration (180 l/day) GFR=Glomelural Filtration Rate ( ml/min) Factors determining filtration 1. properties of glomerular membrane (extension, permeability) 2. effective filtration pressure 3. properties of filtrating substances 7

8 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 ( nm) 2. pores between podocytes (25 nm). 3. hydrated collagen and protoglycane channels of the basal membrane (3-5 nm) 8

9 Pressure relationship in the kidney vessels hydrostatic pressure 9

10 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 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] 10

11 Properties of filtrating substances Molecular weight Molecular shape, Electrostatic factors The glomerular filtrate is protein-free and lipid-free plasma 11

12 Substance Molecular Molecular sizes Filterability weight filtrate/plasma radius diameter concentration ratio Water Urea Glucose Sacharose Inulin Myoglobin Egg albumin Hemoglobin Albumin Relative filterability Polykationic dextrane Polyanionic dextrane Neutral dextrane Effective molecular radius 12

13 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 13

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. 14

15 Estimation of GFR 15

16 Estimation of GFR inulin clearance: ml/min, creatinin clearance: ml/min Regulation of renal blood flow and glomerular filtration rate RPF (renal plasma flow) Amount of plasma flowing through the kidneys during one min (660 ml/min) RBF= (renal blood flow) Amount of blood flowing through the kidneys during one min (1320 ml/min) 16

17 Normal values RPF: 660 ml/min ( ml/min) RBF: 1300 ml/min ( ml/min) Glomerular Filtration Rate (GFR): ml/min Filtration Fraction (FF= GFR/RPF): ~ 0.2 Urinproduction: ml/day, ml/min Osmolality of the urin: mosm/l ph of the urin: Specific weight of the urin: ( ) Regulation of renal circulation Renal autoregulation: RBF and GFR is fairly constant between arterial pressure values of Hgmm - Local vasoactive metabolites - Tubuloglomerular feedback - - Bayliss-effect 17

18 Relationship between arterial pressure and urine production Pressure diuresis 18

19 TUBULAR FUNCTIONS 19

20 Glomerular filtrate Urine Volume 180 l/day 1.5 l/day Glucose 16 g/day Ø Protein 20 g/day Ø Sodium 700 g/day 5-15 g/day Cells Ø Ø 20

21 Tubular Transport About 99% of filtrated water and more than 90% of the filtrated substances will be resorbed. Additionally some substances will be secreted. Water Kreatinin Sodium Chloride Potassium Bicarbonate Calcium Phosphate Magnesium Glukose Glycin, Hystidin Other amino acids Urea Uric acid oxalate 21

22 Epithelial transport STRUCTURAL POLARITY epithelial cells 1. adhere tightly together 2. separate compartments non-polar cells polar cells tubules (kidney), sacs (gallbladder), canaliculi (liver). Epithelial transport Non-Polar Cell Epithelial cells are polar ISF 22

23 FUNCTIONAL POLARITY Epithelia can transport solutes and water in two directions: Absorption is the transport from some lumenal compartment back into blood. The fluid transported is either isotonic, or hypertonic to plasma. Secretion is transport from blood into a given lumenal compartment. The fluid can be either isotonic or hypotonic. Highly Water Permeable Epithelia: (e.g. proximal tubulus) Iso-osmotic Absorption. Epithelia that transport large amounts of solute and water have long and highly enfolded lateral intercellular spaces. The apical surface area is usually enhanced by long and numerous microvilli called the brush border. It reduces the amount of fluid in one compartment and add fluid to another compartment without changing the ionic composition of either compartment. 23

24 Water Impermeable Epithelia. These epithelia have low water permeability of their apical surfaces. They transport a solution that is strongly hypertonic. Hyper-osmotic Absorption In these epithelia salts are absorbed but not water. The net effect is that salt is removed from the luminal compartment into the interstitial fluid without changing the amount of fluid in each compartment. Examples of this kind of epithelium are the thick ascending limb of the loop of Henle and the distal nephron. In some epithelia water permeability is regulated. Epithelial cells are polarized cells 24

25 Transepithelial transport Transcellular and paracellular ways of transepithelial transport 25

26 Transepithelial transport: 2 membrane 3 compartment model Transepithelial transport can be found in kidney, gastrointestinal tract, exocrine glands, choroid plexus. Solvent drag mechanism Schmidt/Thews: Physiologie des Menschen 27. Auflage 1997 Direction of transports 26

27 Passive transport Facilitated diffusion 27

28 Primary active trasport (ion pumps) Secondary and tertiary active transport 28