GLOMERULAR FILTRATION Glomerulocapillary Membrane Measurement of GFR Factors affecting GFR- & Significance

Urine Formation

Glomerular Capillary Membrane-

Glomerular Capillary Membrane (Cont.) Fenestrations in the Capillary Endothelium. Fixed negative charges on the endothelium. Basement membrane: (Fibrillar mesh of collagen have large spaces & -ively charged Proteoglycan)

Glomerular Capillary Membrane- The Filteration Barrier Layers: Endothelium of the Capillary, Basilar Lamina (Basement Membrane), Podocytes- Epithelial Cells PROVIDES: High Permeability & Filterability of Water, Glucose, Na,--- & High Selectivity of Filterability / Barrier e.g. to plasma proteins ( Thick but porous & selective )

GLOMERULAR FILTRATION Fluid that is virtually free of protein & devoid of cells is filtered from the glomerular capillaries into Bowman’s capsule. / An Ultrafiltration controlled by Glomerulo-Capillary membrane permeability and Starling forces Plasma minus proteins & cells. Main Constituents of the Filtrate:Water & Na+ , K+ , Cl- , HCO3- , Urea, Uric acid, Creatinine, Glucose------

Ultrafiltration: Definition A high pressure filtration through a semipermeable membrane in which colloidal particles are retained while the small sized solutes and the solvent are forced to move across the membrane by hydrostatic forces

Glomerular Filtration Rate GFR is the volume of filtrate produced each minute by all the functioning nephrons in both kidneys. An index of kidney function- helps evaluation of severity & course of kidney disease.

GFR GFR per min=125ml (avg value ) The GFR per hour: 125 ml/min X 60min = 7500 ml/hr. GFR per day: 7500 ml/hr X 24 = 180,000 ml/day ( 180 liters/day ).

Filtration Fraction % of Plasma flow rate. GFR /RPF= FF (GFR is about 20% of RPF ) Renal Plasma Flow= 650ml/min GFR = 125ml/min

GFR For a substance that is freely filtered, neither reabsorbed, nor secreted: Filtration by the Kidney = Rate of excretion in the urine Ps X GFR = Us X V GFR= Us X V /Ps = Cs

Renal Clearance (Cont.) Volume of plasma that is required to supply the substance excreted in the urine per unit time. ( Us X V / Ps )

Criteria for selection of substance For GFR Freely filterable through the Glomeruli Neither reabsorbed nor secreted by the tubules Not metabolized Non toxic Does not affect the GFR Can be estimated --

Inulin Clearance Inulin is ideally suited---

Creatinine Clearance Provides reasonable estimate of GFR. Advantage & Drawback. (Why is creatinine clearance preferred to inulin for clinically estimating GFR ?)

MEASUREMENT OF GFR Following can be used to estimate GFR: Inulin Clearance Creatinine Clearance Plasma Creatinine levels

Plasma Creatinine Estimation Pcr (0.6 – 1.2mg/dl) Inversely Propotional to GFR. e.g If GFR ↓→ ↑ Plasma Creatinine Conc Gives Approximate Changes in GFR.

Serum Creatinine & GFR

FACTORS AFFECTING GFR 1. Capillary Permeability 2. Size of Capillary Bed 3. Hydrostatic & Osmotic Pr Gradients/ (Starling forces)

Factors (Cont.) 1.Permeability: Neutral Subs. With Mol. Diam.<4nm (upto 8nm filtration inversely ∞ diameter) Anionic Subs less filtered than neutral. Cationic more filtered than neutral. ( -ive charges on the glom. capillary wall repel –ively charged subst) 2.Size of Capillary Bed: Affected by Mesangial cell Contraction ( eg Angiotensin, Endoth.,Vasopressin, NE, PAF--------).

Albumin molecule with diameter less than 8 nm does not pass through the glomerular memb easily why?

Factors that affect Mesangial Cells

Factors (Cont.) 3. Hydrostatic & Osmotic Pressures. Net Filteration Pressure is determined by Forces favoring: Glm Hydr Press & Bow. Osmot. Press. Forces Opposing: Glm Osmot./Oncotic & Bow. Hydr. Press

Starling Forces affecting Filtration

GFR = Kf X Net filtration pressure GFR= Kf X (Pg-Pb)- (Πg-Πb) Kf – the glomerular ultrafiltration coefficient

Factors Contributing To GFR (Cont.) Kf—depends on the surface area of the Glomerular Capillaries & the permeability of the Membrane. ↓ Kf → ↓ GFR e.g Renal Diseases, Diabetes Mellitus, Hypertension

Glom. Hydrostatic Pr. Depends on: 1. Arterial Pressure ↓→ ↓ GFR ( small effect due to autoregulation ) 2. Afferent Arteriolar Resistance ↑→↓ GFR e.g ↑ Sympath. Activity, ↑ NE, Endothelin

3. Efferent Arteriolar Resistance— Moderate Constriction→↑ GFR Severe Constriction→ ↓ GFR e. g.

Factors that decrease GFR_ Summary 1. ↓ RBF →↓ Glomerular hydrostatic pressure ( Pg ) ↓ GFR. May result from: ↓ AP, ↑ Afferent, ↓ Eff arteriolar resistance 2.↑ Pb (Bowmans hydr.press) e.g. Urinary tract obstruction (renal stone) 3. Plasma Oncotic pressure (Change in Conc. of plasma proteins) 4. Changes in Kf

Learning Outcomes Draw a labelled diagram of the Glomerulus, define glomerular filtration & filtration fraction Depict diagrammatically the components of the glomerulo-capillary membrane Describe the characteristics of glomerular capillaries and compare glomerular capillaries with the systemic capillaries. Illustrate diagrammatically forces causing filtration at the glomerular capillaries Explain the starlings forces that affect net filtration pressure State the main determinants of GFR Explain the role of each determinant in alteration of GFR State how changes in afferent & efferent arteriolar resistance can affect RPF & GFR

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