GLOMERULAR FILTRATION Lecture – 2 Dr. Zahoor
Basic Renal Processes • Glomerular filtration • Tubular reabsorption • Tubular secretion Urine results from these three processes.
Glomerular filtration • Is the first step in urine formation. • Definition:Glomerular filtration is the transfer of fluid and solutes from the glomerular capillaries into Bowman's capsule due to pressure gradient.
GLOMERULAR FILTRATION • Glomerular Filtration occurs through glomerular membrane. • Glomerular membrane has 3 layers: 1. Glomerular capillary endothelial cells 2. Basement membrane 3. Inner layer of Bowman’s capsule – epithelial cells • Important – When blood passes through glomeruli, blood cells (RBC, WBC, Platelet) and plasma protein are not filtered.
Filtration silt Layers of Glomerular Membrane
GLOMERULAR FILTRATION Glomerular membrane is more permeable than capillaries elsewhere. • WHY ? Because i). Glomerular capillary wall has single layer of endothelial cells. It is perforated by many large porescalledFenestrations, that makes it 100 time more permeable to water and solutes than other capillaries in the body.
GLOMERULAR FILTRATION (cont) ii). Basement membrane – it does not have cells, but is composed of collagen and glycoprotein. Glycoprotein are negatively charged. iii). Inner layer of Bowman’s capsule – epithelial cells. Epithelial cells are called Podocytes. Each podocyte has foot processes. Narrow silts between adjacent foot processes are known as Filtration silts, they allow the fluid to enter the lumen of Bowman’s capsule.
GLOMERULAR FILTRATION (cont) • Three Forces are involved in glomerular filtration; 1. Glomerular capillary blood pressure - 55mmHg (Favors filtration) (PGC) 2. Plasma Colloid Osmotic Pressure – 30mmHg (Opposes filtration) (πGC) 3. Bowman’s Capsule Hydrostatic – 15mmHg (Opposes filtration) Pressure (PBS) Net filtration pressure = PGC - (πGC + PBS) Net filtration pressure = 55 – (30+15) = 10 mmHg
FILTRATION IMPORTANT • Filtration through glomerular membrane also depends on size, molecular weight and electrical charge. E.g. Albumin – 6 nanometer • Pores in capillary – 8 nanometer • But Albumin is not filtered due to its negative charge, it is repulsed by basement membrane negative charges.
FILTRATION - APPLIED • In kidney disease, we get proteinuria (protein and urine). WHY? • Because negative charge on basement membrane are lost, therefore, albumin is filtered and lost in urine.
GLOMERULAR FILTRATION RATE What is GLOMERULAR FILTRATION RATE [GFR]? It is filtrate produced by all the nephrons of both kidneys per minute. • Normal GFR = 125ml/min OR 180 liters/day • In female, GFR = 115ml/min OR 160 liters/day
GLOMERULAR FILTRATION RATE • GFR depends on 1. Filtration Pressure 2. Glomerular Surface Area 3. Permeability of Glomerular Membrane • These properties of Glomerular membrane (surface area and permeability) are referred as filtration coefficient (Kf). • GFR = Kf × net filtration pressure
GLOMERULAR FILTRATION RATE • Factors affecting GFR 1-Increased Glomerular Capillary Hydrostatic Pressure (PGC) -> increase GFR 2-Increase colloid osmotic Pressure (πGC)-> decrease GFR e.g. Dehydration, Diarrhea 3-Increase Bowman’s capsule Pressure (PBS)->decrease GFR e.g. urinary tract obstruction, enlarged prostrate
GLOMERULAR FILTRATION RATE • Other factors 1. If afferent arteriole is constricted by epinephrine, norepinephrine, Endothelin (increased resistance), blood flow will decrease, therefore, GFR will decrease 2. If afferent arteriole dilate by Nitric oxide, Prostaglandin(decreased resistance), blood flow will increase, therefore, increase GFR 3. If efferent arteriole constrict by Angiotensin- II, pressure in glomeruli will increase, therefore, increase GFR
Adjustments of Afferent Arteriole Caliber to Alter The GFR
GFR IS AFFECTED BY CHANGES IN FILTRATION COEFFICIENT • Filtration coefficient (Kf) depends on glomerulus surface area and permeability of glomerular membrane. • Kf can be modified by contractile activity in the glomerular membrane by mesangial cells and Podocytes, foot processes in Bowman capsule (physiological) .
GLOMERULAR FILTRATION RATE APPLIED • Kf can be reduced by pathological process e.g. Diabetes mellitus, Hypertension, Glomerulonephritis • If Kf decreased – decreased GFR – in hypertension, diabetes mellitus, GMN, reduced Kf occurs due to increased thickness of glomerular basement membrane and damage to glomeruli.
AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR • There is AUTOREGULATION mechanism in kidney by which it maintains constant blood flow by maintaining constant blood pressure. • Autoregulation is done when systemic BP is in the range of 80- 180 mmHg.
AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR • If GFR increase due to increased BP, it will be reduced to normal by constricting the afferent arteriole. • If GFR decrease due to decreased BP, afferent arteriole will be dilated to increase blood flow and bring GFR back to normal.
AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR • How kidneys maintain the constant BP ? By altering the diameter of Afferent arteriole , there by adjusting the flow to glomeruli . • Auto regulation is done by TWO mechanism 1) Myogenic mechanism 2) Tubulo glomerular feed back mechanism. We will study each one
AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR • Myogenic mechanism • Myogenic means muscle response. • Arterial vascular smooth muscle contracts in response to stretch accompanying increased pressure with in vessel, therefore, afferent arteriole constricts and decreases blood flow. • But when BP decreases, there is relaxation of afferent arteriole, therefore, increase blood flow occurs in the glomerulus.
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 (afferent arteriole)
AUTO-REGULATION MECHANISM IN KIDNEY FOR GFR 2)Tubulo glomerular feed back mechanism • It involves Juxta glomerular apparatus (found by Afferent and Efferent arteriole and DCT, Macula Densa Cells). • So, if GFR increases due to increased BP, more fluid will pass to DCT, therefore, increase Na+ delivery to DCT. • In response to that Macula Densa cells release ATP and Adenosine, both act locally by paracrine way and increase calcium entry to afferent arteriole and cause constriction, therefore, reducing glomerular blood flow and returning GFR to normal.
IMPORTANCE OF AUTO REGULATION • As Myogenic and Tubulo glomerular feedback mechanism work for auto regulation, therefore, they prevent changes in GFR. • If no auto regulation, changes in GFR will occur and will lead to imbalance of fluid and electrolytes and waste product excretion. NOTE – If mean arterial BP is less than 80mmHg or more than 180mmHg, auto regulation will NOT take place and there will be changes in GFR.
BLOOD SUPPLY TO THE KIDNEY • Kidney normally receives 20-25% of cardiac output i.e. 1.1 liter of blood flow per minute. • About 625ml/min of plasma flows to the kidney. • 20% of plasma is filtered and converted to glomerular filtrate and passes to Bowman’s Capsule, therefore, average GFR is 125ml/min. • The remaining [80%] passes to efferent arterioles then into the peritubular capillaries
BLOOD SUPPLY TO THE KIDNEY IMPORTANT POINTS • Renal blood flow 1.1L (1100ml/min) • Renal plasma flow 625ml/min • GFR 125ml/min • Kidney composes less than 1% of total body weight but gets 20-25% cardiac output. WHY? Because of its function i.e. regulating water , electrolyte balance and getting rid of waste products.
MEASUREMENT OF GFR • Substances used to measure GFR 1. Inulin – polymer of fructose, it is filtered, but not reabsorbed, not secreted by renal tubule 2. Creatinine – it is secreted, but some may be reabsorbed , therefore, not so accurate Inspite of this clearance of endogenous creatinine is frequently used to measure GFR
What is a Glomerular Filtration Fraction? • The Filtration Fraction (FF) is the ratio of the GFR to the renal plasma flow (GFR/RPF). • Filtration fraction = GFR/Renal Plasma flow = 125/625 = 0.2 = 20%