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Lecturer of Medical Physiology Kidney By Dr. Abdel Aziz M. Hussein Lecturer of Medical Physiology

Given these structures: 1. basement membrane 2. fenestra 3. filtration slit Choose the arrangement that lists the structures in the order a molecule of glucose encounters them as the glucose passes through the filtration membrane to enter Bowman’s capsule. a. 1,2,3 b. 2,1,3 c. 2,3,1 d. 3,1,2 e. 3,2,1

Urine Formation

Glomerular Filtration Def., Means the bulk flow of a solvent through a filter carrying with it the solutes that are small enough to pass through the filter.

Glomerular Filtration Capillary endothelium Blood Capillary endothelium Basement Membrane Podocytes slits Bowman Capsule

Glomerular Filtration Def., It is an ultrafiltration since it is plasma minus plasma protein and cellular elements while simple filtration excludes only cellular elements.

Glomerular Filtration Capillary endothelium Blood Capillary endothelium Basement Membrane Podocytes slits Blood Cells Bowman Capsule Plasma proteins Plasma solutes

Glomerular Filtration Dynamics: Glomerular Filtration is formed by the forces of filtration as many capillary filtrate in the body (Starling's forces of filtration). They are 4 forces; 2 Hydrostatic pressures 2 Oncotic pressures

Glomerular Filtration Glomerular Oncotic Pressure (Gπ) Glomerular Hydrostatic Pressure (Gp) Glomerular capillary Capillary endothelium Basement Membrane Podocytes slits Bowman Capsule Bowman oncotic Pressure (B π) Bowman Hydrostatic Pressure (Bp)

Glomerular Filtration Gπ = 32 mmHg Gp = 60 mmHg Gp = 18 mmHg Bπ = 0 mmHg

Glomerular Filtration GFR is determined by Starling's principle; ″The rate & direction of fluid movement is proportional to the algebraic sum of hydrostatic & oncotic pressures″ So, GFR α (hydrostatic pressure – oncotic pressure) GFR α { (Gp- Bp) – (Gπ – Bπ)} KF = filtration coefficient

Glomerular Filtration Net filtering force {60-(32+18)} = 10 mmHg and GFR = 120 mL/ min

Glomerular and Systemic Filtration Glomerular filtration Systemic capillary filtration Capillary Exchange Area 1.6 m2 – of which only 2-3% are available for filtration (320-480 cm2) 1000 m2 of systemic capillary 25%- 35% are opened  250- 350 m2 Pulmonary capillary Surface area is 60 m2. Filtration Rate 180 L/day 20 L/day are filtered at arterial end, of which 18L are reabsorbed at venous end & 2L by lymphatic. Capillary Hydrostatic Pressure 45-60 mmHg 32 mmHg at art. end & decrease to 15 mmHg at venous end Osmotic Pressure of Plasma Protein 25 mmHg at afferent end of capillary & rises to 37 mmHg at efferent end of capillary. 25 mmHg along the whole length Filtration Coefficient 4mL/min/1 mmHg/100 gm 0.01mL/min/1mmHg/100 gm.

Glomerular Filtration Gp = 60 mmHg Gπ = 37 mmHg Gπ = 25 mmHg

Systemic Filtration

Glomerular Filtration Rate (GFR)

Glomerular Filtration Rate Def., Volume of plasma filtered by both kidney per unit time Value: 125 ml/min 180 L/day or 60 nl/min for single nephron (SNGFR). Filtration fraction: is part of RPF filtered in Glomeruli GFR 125 ml/min = = = 1/5 or 20% RPF 650 ml/min

RPF 650 ml/min FF= 120/ 650 = 20% GFR 120 ml/min RPF 649 ml/min Urine flow rate 1 ml/min

Glomerular Filtration Rate Significance of High GFR: To ensure processing of plasma (3L) about 60 times/day (since daily GFR = 180L/day  prevents accumulation of metabolites. Causes of high GFR: High filtration coefficient: KF is volume of fluid filtered /min/ mmHg pressure difference across the membrane

Glomerular Filtration Rate Causes of high GFR: High filtration coefficient: For the kidney  4 ml/ min/ mmHg/ 100 gm tissue or 12 ml/ min/ mmHg/ 300gm (both kidneys). For systemic capillary  0.01 ml/ min/ mmHg/ 100gm tissue. This is due to high permeability of the glomerular membrane for same hydrostatic pressure gradient.

Glomerular Filtration Rate Causes of high GFR: 2) High capillary hydrostatic P.: It is about 45- 60 mmHg in glomerular capillary In systemic capillary 32 mmHg at arterial end and 15 mmHg at venous end Causes of high GP: Renal artery → short, wide, direct branch from aorta. Afferent arteriole → straight branch of interlobular artery Efferent arteriole → narrower than afferent arteriole Glomerular capillaries →present between two arteries

Causes of High Gp

Causes of High Gp

Glomerular Filtration Rate Causes of high GFR: 3) High RPF.: It is about 600ml/ min. This high RBF eventually leads to high GFR. RBF

Glomerular Filtration Rate Factors Affecting GFR: Glomerular hydrostatic pressure About 45 – 60 mmHg Help GFR Bowman’s capsular hydrostatic pressure About 18 mmHg Oppose GFR Oncotic pressure of plasma protein About 32 mmHg Renal plasma flow (RPF) About 650 ml/min Filtration coefficient About 4 ml/min/ 1mmHg/ 100 gm

1. Glomerular Hydrostatic P. It is high compared to systemic capillary Causes of high GP Factors affecting: A) Systemic ABP: Between 80- 180 mmHg ( no change) Less than 80 mmHg → ↓ Gp More than 180 mmHg →↑ Gp B) Balance between afferent and efferent arterioles resistance

2. Bowman Hydrostatic P. It is about 18 mmHg  helps to maintain renal tubules patent. Acts as a driving force to propel glomerular filtrate along whole length of renal tubules. If increased e.g. in ureteric obstruction  decrease GFR.

Bp Increased Bp

3. Oncotic P. of Plasma Proteins Normally 32 mmHg. If changed  marked effect on GFR. Increase plasma oncotic pressure  decrease GFR. As in: Marked hyperproteinemia as in multiple myeloma. Dehydration, hemorrhage, sever burns & chronic diarrhea.

Gπ

3. Oncotic P. of Plasma Proteins Leakage of plasma albumin from glomerular membrane in some pathological conditions  decrease plasma oncotic pressure & increase Bowman’s oncotic pressure  increase GFR.

4. Renal Plasma Flow RPF affect indirectly the plasma oncotic pressure Increase RPF  maintain normal plasma oncotic pressure and filtration equilibrium is achieved too late  helps GFR. Decrease RPF  elevates plasma oncotic pressure  decrease GFR.

High RPF

5. Filtration Coefficient It is the effectiveness of the permeability of the barrier. It depends on: Hydraulic conductivity (water permeability of the barrier). Effective filtration surface area

5. Filtration Coefficient 2. Effective filtration surface area is affected by: Total number of functioning glomeruli. State of intraglomerular mesangium. Their contraction (e.g. by AII)  decrease effective filtration area & their relaxation (e.g. by dopamine)  increase effective surface area.

Effect of Afferent and Efferent Arteriolar Resistance on: RPF, GFR, and Filtration Fraction (FF)

Change in Preglomerular Resistance Or (afferent arteriole diameter) V.D. of afferent arterioles ↑ Gp ↑ RPF FF = no change ↑ GFR

Change in Preglomerular Resistance Or (afferent arteriole diameter) V.C. of afferent arterioles ↓ Gp ↓ RPF FF = no change ↓ GFR

Change in Postglomerular Resistance Or (efferent arteriole diameter) V.D. of efferent arterioles ↓ Gp ↑ RPF FF = decrease ↓ GFR

Change in Postglomerular Resistance Or (efferent arteriole diameter) V.C. of efferent arterioles ↑ Gp ↓ RPF FF = Increase ↑ GFR

RPF GFR FF (GFR / RBF) VC --  constant VD  Afferent (Preglomerular resistance) Efferent (Postglomerular resistance RPF GFR FF (GFR / RBF) VC --  constant VD 

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