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 Kf πc Fluids in the "Potential Spaces" of the Body
Safety Factors That Normally Prevent Edema Low compliance in IF 3 mmhg Lymph Flow 7mmHg Safety factor "Washdown of IF Protein 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
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 Function of the Kidney Terminology
Micturation
Bowman s capsules - with glomerulus
The filtration barrier - podocytes basal lamina pedicel filtration slit fenestrated endothelium basal lamina podocyte fenestrated endothelium secondary process (pedicel) primary process filtration slit podocyte cell body
Detailed structure of the filtration system Endoth cell nucleus Podocyte process Capillary Basement membrane Basement membrane F BM E Capillary Capillary Fenestrations Fenestrations Endoth 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. mm Hg 40 30 20 P GC -P BC Glomerular hydrostatic pressure, P GC, is high and relatively constant 45 mmhg. This is offset by a pressure in Bowman s capsule P BC 10 mm Hg Net filtrative force is: 35 mm Hg 10 0 aff. art eff. art.
THE GLOMERULUS - THE STARLING EQUILIBRIUM mm Hg 40 30 20 10 Net filtration force Π GS P GC -P BC Glomerular hydrostatic pressure, P GC, is high and constant 45 mmhg. This is offset by a pressure in Bowman s capsule P BC 10mmHg Net filtrative force is: 35 mm Hg Osmotic pressure, Π GS, 25 mm Hg. Due to the large net filtration of fluid Π GS increases along the capillary to 35 mm Hg to achieve a balance of forces. 0 aff. art eff. art.
FILTRATION FRACTION Filtration fraction is an important expression of the extent of glomerular filtration. It is the ratio: Filtration fraction = Glomerular filtration rate Renal plasma flow Renal blood flow 1250 ml/min glomerulus tubule GFR 125 ml/min RPF 750 ml/min Efferent Arteriole 625 ml/min 124 ml/min renal vein It is the fraction of renal plasma flow that is filtered at the glomerulus Urine 1 ml/min
FILTRATION FRACTION an example Glomerular filtration rate (GFR) is about: 125 ml/min Renal blood flow is about: 1250 ml/min Renal plasma flow (RPF) is about: 750 ml/min Remember: plasma volume is about 60% of total blood volume Thus, in this example filtration fraction is: 125 750 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 RBF also modifies solute and water reabsorption and delivers nutrients to nephron cells. Renal blood flow is autoregulated between 90 and 180 mm Hg by varying renal vascular resistance (RVR) i.e. the resistances of the interlobular artery, afferent arteriole and efferent arteriole Flow, l/min 1.5 1.0 0.5 0 Renal blood flow GFR 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 pressure Flow increases Remember: Flow α 1 r 4
RENAL BLOOD FLOW - AUTOREGULATION 1. Myogenic hypothesis When arterial pressure increases the renal afferent arteriole is stretched Increase of arterial pressure Flow increases Vascular smooth muscle responds by contracting thus increasing resistance Increase of vascular tone Flow returns to normal
RENAL BLOOD FLOW - AUTOREGULATION 2. Tubuloglomerular feedback Alteration of tubular flow (or a factor in the filtrate) is sensed by the macula densa of the juxtaglomerular 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?). 4. R a GFR 1. GFR 2. filtrate 3.signal from JGA
27: Tubular Processing of the Glomerular Filtrate
10mmHg
First Defense line: TGF Second Defanse line: GTB GFR regulation Reabsorption regulation ΔP ΔUO AgII
Use of Clearance Methods to Quantify Kidney Function
C = U * V/ P GFR = Cinulin FF= GFR / RPF RPF= CPAH