By: Dr. Foadoddini Department of Physiology & Pharmacology Birjand University of Medical Sciences Body fluids and Renal physiology
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Volume and Osmolality of Extracellular and Intracellular Fluids in Abnormal States
Pc Edema π C Kf Fluids in the "Potential Spaces" of the Body
Safety Factors That Normally Prevent Edema Low compliance in IF 3 mmHg Safety factor Lymph "Washdown“ Flow of IF Protein 7mmHg 7mmHg
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Blood Supply to the Kidneys • Blood travels from afferent arteriole to capillaries in the nephron called glomerulus • Blood leaves the nephron via the efferent arteriole • Blood travels from efferent arteriole to peritubular capillaries and vasa recta
Internal Anatomy
Function of the Kidney • Terminology • Blood is filtered in the nephrons • The cortex of each kidney contains ± 1,2 million nephrons • The nephron consists of a renal corpuscle and a renal tubule • The renal tubule consists of the convoluted tubule and the loop of Henle • The main filter of the nephron is glomerulus which is located within the Bowman's capsule
Micturation
Bowman’s capsules - with glomerulus
The filtration barrier - podocytes filtration pedicel slit basal lamina fenestrated endothelium basal lamina podocyte filtration slit fenestrated podocyte endothelium cell body secondary primary process process ( pedicel )
Detailed structure of the filtration system Podocyte Endoth process cell nucleus Capillary Basement F membrane BM E Basement Capillary membrane Fenestrations Capillary Endoth Fenestrations cell nucleus
The filtration barrier - pedicels Bowman’s space pedicel filtration slit capillary
Control of Kf • Mesangial cells have contractile properties, influence capillary filtration by closing some of the capillaries – effects surface area • Podocytes change size of filtration slits
GLOMERULAR FILTRATION The glomerular filtration rate (GFR) is about 125 ml/min in a normal adult � The first step in the formation of urine is the production of a plasma ultrafiltrate. � The ultrafiltrate is cell and protein-free and the concentration of small solutes are the same as in plasma. � The filtration barrier restricts movement of solutes on a basis of size and charge. Molecules < 1.8 nm freely filtered; >3.6 nm not filtered Cations are more readily filtered than anions for the same molecular radius. Serum albumin has a radius if about 3.5 nm but its negative charge prevents its filtration In many disease processes the negative charge on the filtration barrier is lost so that proteins are more readily filtered - a condition called proteinuria
10mmHg
THE GLOMERULUS - THE STARLING EQUILIBRIUM The glomerulus is unusual with respect to most capillary beds. Glomerular hydrostatic pressure, P GC , is high and relatively constant mm Hg ≈ 45 mmHg. P GC -P BC 40 This is offset by a pressure in Bowman’s capsule P BC ≈ 10 mm Hg 30 Net filtrative force is: ≈ 35 mm Hg 20 10 0 aff. art eff. art.
THE GLOMERULUS - THE STARLING EQUILIBRIUM Glomerular hydrostatic pressure, P GC , is high and constant ≈ 45 mmHg. mm Hg This is offset by a pressure in P GC -P BC 40 Bowman’s capsule P BC ≈ 10mmHg Net filtrative force is: ≈ 35 mm Hg Π GS 30 Osmotic pressure, Π GS , ≈ 25 mm Hg. Due to the large net filtration of fluid 20 Net filtration Π GS increases along the capillary to 35 force mm Hg to achieve a balance of forces. 10 0 aff. art eff. art.
FILTRATION FRACTION Filtration fraction is an important expression of the extent of glomerular filtration. Glomerular filtration rate It is the ratio: Filtration fraction = Renal plasma flow Renal blood flow 1250 ml/min RPF It is the fraction of renal 750 ml/min plasma flow that is glomerulus filtered at the glomerulus Efferent GFR Arteriole 125 ml/min renal 625 ml/min vein tubule 124 ml/min Urine 1 ml/min
FILTRATION FRACTION an example Glomerular filtration rate (GFR) is about: 125 ml/min Remember: plasma volume is about Renal blood flow 60% of total blood volume is about: 1250 ml/min Renal plasma flow (RPF) is about: 750 ml/min 125 Thus, in this example filtration fraction is: 750 ≈ 0.17 GFR and RPF can be measured separately using clearance methods
RENAL BLOOD FLOW (RBF) Renal blood flow is ≈ 1.25 l/min -i.e. about 25% of the cardiac output This is a very large flow relative to the weight of the kidneys ( ≈ 350 g) � RBF determines GFR Flow, l/min 1.5 � RBF also modifies solute and water reabsorption and delivers nutrients to nephron cells. 1.0 Renal blood flow � Renal blood flow is autoregulated 0.5 between 90 and 180 mm Hg by varying renal vascular resistance (RVR) � i.e. the resistances of the interlobular 0 GFR artery, afferent arteriole and efferent arteriole 0 100 200 Arterial blood pressure, mm Hg
RENAL BLOOD FLOW - AUTOREGULATION Autoregulation effectively uncouples renal function from arterial blood pressure and ensures that fluid and solute excretion is constant. Two hypotheses have been proposed to explain autoregulation 1. Myogenic hypothesis When arterial pressure increases the renal afferent arteriole is stretched Increase of arterial Flow pressure increases Remember: 1 Flow α r 4
RENAL BLOOD FLOW - AUTOREGULATION 1. Myogenic hypothesis When arterial pressure increases the renal afferent arteriole is stretched Flow Increase of arterial increases pressure Vascular smooth muscle responds by contracting thus increasing resistance Increase of vascular Flow returns tone to normal
RENAL BLOOD FLOW - AUTOREGULATION 2. Tubuloglomerular feedback 3.signal from JGA 4. ↑ R a Alteration of tubular flow (or a factor ↓ GFR in the filtrate) is sensed by the macula densa of the juxtaglomerular 1. ↑ GFR apparatus (JGA) and produces a signal that alters GFR. It is unclear what is the factor (NaCl reabsorption?) or the nature of the signal (renin?). 2. ↑ filtrate
27: Tubular Processing of the Glomerular Filtrate
10mmHg
GFR regulation First Defense line: TGF Reabsorption regulation Second Defanse line: GTB Δ UO Δ P AgII
Use of Clearance Methods to Quantify Kidney Function
C = U * V/ P GFR = C inulin FF= GFR / RPF RPF= C PAH
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