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بسم الله الرحمن الرحيم. GLOMERULAR FILTERATION . Dr.Mohammed Sharique Ahmed Quadri Assistant prof. Physiology Al Maarefa College. OBJECTIVES . Identify three basic processes involved in urine formation; glomerular filtration, tubular reabsorption and tubular secretion
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بسم الله الرحمن الرحيم GLOMERULAR FILTERATION • Dr.MohammedSharique Ahmed Quadri • Assistant prof. Physiology • Al Maarefa College
OBJECTIVES • Identify three basic processes involved in urine formation; glomerular filtration, tubular reabsorption and tubular secretion • Define GFR and quote normal value in men and women • Describe the composition of the glomerular filtrate • Detect the structural & functional peculiarities of the glomerular filtration membrane • Outline the factors controlling GFR • Given capillary and Bowman’s capsule hydrostatic and oncotic pressures calculate the net filtration pressure. • Correlate between net filtration pressure along glomerulus and plasma flow • List the characteristics that a compound must have before it can be used for measuring GFR e.g. Inulin, creatinine etc. • Given the data, calculate GFR .
Glomerular filtration Tubular reabsorption Tubular secretion Urine results from these three processes. Basic Renal Processes
Glomerular filtration • Is the first step in urine formation. • Definition:Glomerular filtration is the transfer of fluid and solutes from the glomerular capillaries along a pressure gradient into Bowman's capsule.
Composition of the Glomerular Filtrate • It is the fluid within the Bowman’s capsule that is essentially cell-free and protein-free and contains crystalloids in virtually the same concentrations as in the plasma. • It is free from: • Blood cells • Protein • Protein-bound molecules (calcium, fatty aids, amino acids)
Glomerular Filtration • Fluid filtered pass through three layers of the glomerular membrane • Glomerular capillary wall • Single layer of endothelial cells • More permeable to water and solutes than capillaries elsewhere in the body • Basement membrane • Acellular gelatinous layer • Composed of collagen and glycoproteins • Inner layer of Bowman’s capsule • Consists of podocytes that encircle the glomerulus tuft
Glomerular Capillary Filtration Barrier • Endothelium (fenestrated) • Basement Membrane negatively charged, restriction site for proteins • Epithelial Cells, restriction site for proteins. Characterized by foot-like processes (podocytes).
Filtration • Despite the three layers of the barrier, the glomerulus filters several hundred times as much water and solutes as the usual capillary membrane. • Even with this high rate of filtration, the glomerular capillary membrane normally prevents filtration of plasma proteins.
Glomerular Capillary Membrane Filterability depends on: • Size of the molecule • the pores of the glomerular membrane are about 8 nanometers (80 angstroms) • Electrical Charge of the molecule • positively charged molecules are filtered much more easily than negatively charged molecules of equal molecular size. • the negative charges of the basement membrane and the podocytes provide an important means for restricting negatively charged molecules, including the plasma proteins. • Diameter of albumin is only about 6 nanometers, but negatively charged.
Clinical Significance of Proteinuria • Early detection of renal disease in at-risk patients • Hypertension: Hypertensive renal disease • Diabetes: Diabetic nephropathy • Pregnancy: gestational proteinuric hypertension (pre-eclampsia) • annual “check-up”: renal disease can be silent • Assessment and monitoring of known renal disease
Microalbuminuria • Definition: urine excretion of > 25-30 but < 150mg albumin per day • Causes: early diabetes, hypertension • Prognostic Value: diabetic patients with • microalbuminuria are 10-20 fold more • likely to develop persistent proteinuria
Glomerular Filtration Rate (GFR) GFR: The volume of plasma filtered from both kidneys per minute. GFR = 125 ml/min = 180 liters/day Plasma volume is filtered 60 times per day GFR= Filtration Coefficient (Kf) x Net Filtration Pressure(NFP)
Factors Affecting GFR Filtration Coefficient (Kf) Net Filtration Pressure(NFP)
Filtration coefficient • Filtration coefficient (Kf): A measure of the product of the hydraulic conductivity (water permeability)and filtering surface area of the capillaries. • glomerular capillary filtration coefficient = 12.5 ml/min per mmHg, or 4.2 ml/min per mmHg/ 100gm • (400 x greater than in tissues such a muscle)
Increased Glomerular Capillary Filtration Coefficient (Kf) Increases GFR • Normally not highly variable • Kf reduces by reducing the number of functional glomerulus(decrease surface area) or by increasing the thickness BM (reducing its hydraulic conductivity). • Diseases that can reduce Kf and eventually GFR • Chronic hypertension • Diabetes mellitus • Glomerulonephritis
Forces determining Net Filtration Pressure (NFP) • Three physical forces involved • Glomerular capillary blood hydrostatic pressure • Plasma-colloid osmotic osmotic pressure • Bowman’s capsule hydrostatic hydrostatic pressure
1 1 1 GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg GLOMERULAR BLOOD HYDROSTATIC PRESSURE (GBHP) = 55 mmHg 2 2 CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg CAPSULAR HYDROSTATIC PRESSURE (CHP) = 15 mmHg 3 BLOOD COLLOID OSMOTIC PRESSURE (BCOP) = 30 mmHg Afferent arteriole Afferent arteriole Afferent arteriole Proximal convoluted tubule Proximal convoluted tubule Proximal convoluted tubule Efferent arteriole Efferent arteriole Efferent arteriole NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg NET FILTRATION PRESSURE (NFP) =GBHP – CHP – BCOP = 55 mmHg 15 mmHg 30 mmHg = 10 mmHg Glomerular (Bowman's) capsule Glomerular (Bowman's) capsule Glomerular (Bowman's) capsule Capsular space Capsular space Capsular space
Net (effective) Filtration Pressure (NFP) • Definition: = NFP is an algebraic sum of opposing hydrostatic and osmotic forces acting across the capillary • NFP = forces inducing filtration - forces opposing filtration • NFP = ( PGC+ BC) - ( PBC+ GC) • PGC Glomerular hydrostatic pressure • GC Glomerular oncotic pressure • PBC Bowman’s capsule hydrostatic pressure • BC Bowman’s capsule oncotic pressure • NB: as there is virtually no protein, BC ~ 0, • therefore NFP = PGC - (PBC + GC) BC PGC PBC GC
Glomerular Filtration Rate • Net filtration pressure = glomerular capillary blood pressure – (plasma-colloid osmotic pressure + Bowman’s capsule hydrostatic pressure) For example: 55 mm Hg – (30 mm Hg + 15 mm Hg) = 10 mm Hg • Glomerular filtration rate (GFR) • Depends on • Net filtration pressure • How much glomerular surface area is available for penetration • How permeable the glomerular membrane is
Unregulated influences on the GFR • Increased Bowman’s Capsule Hydrostatic Pressure (PBc) Decreases GFR • Do not serve as physiological regulator of GFR • Increase of PBccan be caused by • Tubular Obstruction • kidney stones • tubular necrosis • Urinary tract obstruction • Prostatic enlargement
Unregulated influences on the GFR • plasma colloid osmotic pressure • Do not serve as physiological regulator of GFR • Plasma-colloid osmotic pressure • Severely burned patient ↑ GFR • Dehydrating diarrhea ↓ GFR
Glomerular Filtration Rate • Controlled adjustments in GFR • Glomerular capillary hdrostatic pressure can be controlled to adjust GFR to suit the body’s needs • Two major control mechanisms • Extrinsic sympathetic control -by adjusting the constriction of afferent/efferent arterioles • Mediated by sympathetic nervous system input to afferent arterioles • Baroreceptor reflex • Autoregulation (aimed at preventing spontaneous changes in GFR) • Myogenic mechanism • Tubuloglomerular feedback (TGF)
Adjustments of Afferent Arteriole Caliber to Alter The GFR
Baroreceptor Reflex Influence on the GFR
Calculation of Glomerular Filtration Rate (GFR) • GFR = Filtration Coefficient (Kf ) x Net Filtration Pressure (NFP) • GFR = 12.5 x 10 = 125 ml/min = 180 liters/day • GFR in females is less (110 ml/min) • Plasma volume is filtered 60 times per day
Autoregulation The major function of autoregulation in the kidneys is to maintain a relatively constant GFR and renal blood flow despite considerable arterial pressure fluctuations that can occur. Autoregulation: • Myogenic autoregulation • Tubuloglomerular feedback
Myogenic Mechanism Vascular smooth muscle contraction in response to increased stretch Arterial Pressure Stretch of Blood Vessel Cell Ca++ Permeability Vascular Resistance Intracell. Ca++ Blood Flow
Macula Densa Feedback (Tubuloglomerular feedback) GFR Distal NaCl Delivery Macula Densa NaCl Reabsorption (macula densa feedback) Afferent Arteriolar Resistance GFR (return toward normal)
What is a Glomerular Filtration Fraction? • The Filtration Fraction (FF) is the ratio of the GFR to the renal plasma flow (GFR/TRPF). • Renal blood flow = 1.1 L/min • 20-25% of total cardiac output (5 L/min). • Of the 625 ml of plasma enters the glomeruli via the afferent, 125 (the GFR) filters in the Bowman’s capsule, the remaining passing via efferent arterioles into the peritubular capillaries • Filtration fraction = (GFR/TRPF) = 0.2 • So, GFR is About 20% of the Renal Plasma Flow
The filtration fraction The Filtration Fraction (FF) is the ratio of the GFR to the renal plasma flow = (GFR/TRPF).
References • Human physiology by Lauralee Sherwood, seventh edition • Text book physiology by Guyton &Hall,11th edition • Text book of physiology by Linda .s contanzo,third edition