MAJOR FUNCTIONS OF THE KIDNEY REGULATION OF BODY FLUID VOLUME REGULATION OF OSMOTIC BALANCE REGULATION OF ELECTROLYTE COMPOSITION REGULATION OF ACID-BASE BALANCE REGULATION OF BLOOD PRESSURE ERYTHROPOIESIS EXCRETION OF WASTE PRODUCTS AND FOREIGN SUBSTANCES
SYSTEM REQUIREMENTS PROCESS LARGE VOLUME OF FLUID LARGE SURFACE TO VOLUME RATIO CLOSE CONTROL MINIMAL ENERGY COST RETAIN NUTRIENTS
SYSTEM REQUIREMENTS PROCESS LARGE VOLUME OF FLUID: Renal Blood Flow (RBF) = 1.2 L/min, >1700 L/day, 20-25% of cardiac output. Renal Plasma Flow (RPF) = 660 ml/min, 950 L/day Glomerular Filtration Rate (GFR) = 125 ml/min, 180 L/day
SYSTEM REQUIREMENTS LARGE SURFACE TO VOLUME RATIO: 2,000,000 nephrons in the two kidneys Blood Flow: Glomerular Filtration: 1200 ml/min 125 ml/min 0.006 ml/min/nephron 0.000063 ml/min/nephron Excretion Rate: ~1 ml/min ~0.0000005 ml/min/nephron
QUANTITIES OF SOLUTE FILTERED AND EXCRETED Plasma Filtered/day Excreted/day Percent Conc. mm mmoles mmoles Reabsorbed Na 140 25,200 103 99+ Cl 105 18,900 103 99+ HCO 3 25 4,500 2 99+ K 4 720 100 86+ Glucose 5 900 trace 100 Urea 5 900 360 60
uperficially, it might be said that the function of the kidneys is to make urine; but in a more condsidered view one can say that the kidneys make the stuff of philosophy itself. Homer Smith
ANATOMY OF THE NEPHRONS CORTEX Juxtamedullary nephron juxtaglomerular apparatus Cortical nephron distal tubule proximal tubule glomerulus MEDULLA OUTER INNER Henle s loop thick segment thin segment Collecting tubule
BASIC NEPHRON FUNCTIONS 1. Filtration 2. Reabsorption 1 3. Secretion 4. Excretion 4 2 3
SOLUTE-NEPHRON INTERACTIONS FILTRATION ONLY FILTRATION + REABSORPTION FILTRATION + SECRETION Inulin Iothalamate Na. Cl, Urea Glucose Hippurates, Penicillin Furosemide
Bowman s drawing of human glomerulus and associated vessels. 1842
PRESSURES IN THE RENAL CIRCULATION Renal Artery Afferent Arteriole Glomerular Capillary Efferent Arteriole 120 H.P. Peritubular Capillary Intrarenal Vein Renal Vein 100 mm Hg 80 60 40 20 π b
HYDROSTATIC AND COLLOID OSMOTIC PRESSURES IN THE CAPILLARY BEDS Aff. arteriole Glomerular Capillaries H.P. > π b Filtration occurs. Eff. arteriole Peritubular Capillaries π b > H.P. Absorption occurs.
FILTRATION OF LARGE MOLECULES
EFFECT OF DISEASE ON GLOMERULAR PERMEABILITY TO LARGE MOLECULES Macromolecule Molecular Radius Fractional Clearance (A) (U/P) m /(U/P) in Normal Values Albumin 36 <0.001 Neutral Dextran 36 0.19 Dextran Sulfate 36 0.015 Experimental Glomerular Nephritis Neutral Dextran 36 0.14 Dextran Sulfate 36 0.24
FILTRATION PRESSURES The major force causing filtration is the hydrostatic pressure in the glomerular capillary bed, P gc. Pgc 60 mm Hg It is opposed by a smaller hydrostatic pressure within the tubule, P t. Pt 15 mm Hg ΔP is the hydrostatic pressure gradient across the capillary wall: ΔP = Pgc - Pt 60-15 45 mm Hg Filtration is also opposed by the colloid osmotic pressure of the blood, π b. P gcpt π b π b = 32 mm Hg (mean)
FILTRATION PRESSURES P f is the net filtration pressure. P f = P gc - π b - P t P f = 13 mm Hg (mean) The magnitude of the glomerular filtration rate, GFR, is also a function of the hydraulic permeability of the membrane, L p, and its surface area, A. The filtration coefficient, k f, is the product of these two terms. k f = L p A P gc P t π b k f ~ 9 ml/min/mm Hg GFR = k f P f GFR = 120 ml/min
FILTRATION PRESSURE PROFILES mm Hg P f π b Δ P Glomerular capillary length Δ P = P gc - P t = the hydrostatic pressure gradient across the capillary membrane. Δ P drops only slightly from beginning to end of capillary bed. π b rises because the filtration of fluid without protein increases the protein conc. in the plasma remaining in the capillaries. Thus P f declines from beginning to end of capillary bed.
FILTRATION PRESSURES PROFILES A P f Δ P B mm Hg π b Normal curves Fall in Δ P C Glomerular capillary length D RBF rapid rise in π b curve k f slow rise in π b curve
EFFECTS OF ARTERIOLAR CONSTRICTION A. Afferent B. Efferent R aff R eff R aff R eff RBF RBF P gc p b P gc P gc P gc p b π b GFR GFR
THE JUXTAGLOMERULAR APPARATUS afferent arteriole macula densa efferent arteriole distal tubule smooth muscle endothelial cells granular cells lacis cells glomerulus
J.G. APPARATUS IS A MAJOR CONTROL POINT INPUTS: Neural Humoral Arterial Tubular Pressure Fluid OUTPUTS: Δ RBF Δ GFR Δ RENIN EFFECTS: Δ NaCl & Water Exc. Δ Blood Volume Δ Angio II Δ H.P.
FACTORS AFFECTING THE ARTERIOLES I. RESTING TONE II. NEURAL INNERVATION Sympathetic vasoconstrictor fibers innervate both arterioles. III. EXTERNAL HUMORAL FACTORS Catecholamines. α-receptors predominate. Thus response is vasoconstriction. Acetycholine. Vasodilation Pyrogens produced by bacteria etc. Vasodilation. IV. INTERNAL HUMORAL FACTORS. Angiotensin II: both external and internal factor. Vascoconstrictor effect on both arterioles. Prostaglandin E2. Vasodilator. Affects primarily afferent arteriole.
AUTOREGULATION OF RBF AND GFR RBF GFR 1600 200 Autoregulatory Range 1200 150 RBF 800 100 ml/min GFR 400 50 0 0 0 50 100 150 200 Arterial Pressure, mm Hg
MYOGENIC MECHANISM FOR REGULATION OF RENAL BLOOD FLOW FLOW = PRESSURE RESISTANCE P Smooth Muscle Stretch Contraction Resistance Little Change in RBF
TUBULOGLOMERULAR FEEDBACK MECHANISM (TGF) GFR Arterioles Macula densa area Glomerulus Proximal tubule Glomerular cap. H.P. Tubular fluid flow rate [Cl] tf reaching macula densa Adenosine formation Afferent arteriolar resistance RBF
EXTRINSIC REGULATION VS. AUTOREGULATION Sym. N.S. and AII tend to constrict both arterioles and reduce GFR and RBF. Autoregulatory factors (ARF) control aff. arteriole and tend to maintain GFR and RBF constant. When Sym N.S. and AII are elevated, ARF kicks in and prevents large effect on aff. arteriole. Result: Small increase in R aff Larger increase in R eff Small fall in GFR (GFR is protected). Larger fall in RBF.
INTEGRATED CONTROL OF RBF AND GFR Sympathetic Nerves Catecholamines Angiotensin TGF and myogenic response PGE2 - + + R aff RBF R eff RBF GFR _ Sympathetic nerve activity Catecholamines Angiotensin II } RBF + GFR _ PGE2 R aff TGF } RBF + GFR