Glomerular Filtration PDF

Glomerular Filtration Dr Ashwathy  Learning outcomes 15.1 Define GFR. Calculate the same and mention its normal value. 15.2 Define filtration fraction. Calculate the same and mention its normal value. 15.3 Describe the factors determining filtration across glomerular capillar...

Glomerular Filtration Dr Ashwathy  Learning outcomes 15.1 Define GFR. Calculate the same and mention its normal value. 15.2 Define filtration fraction. Calculate the same and mention its normal value. 15.3 Describe the factors determining filtration across glomerular capillaries. 15.4 Define effective filtration pressure. Calculate the same and mention its normal value. 15.5 Explain various factors affecting GFR. 15.6 Describe the regulation of GFR (myogenic theory and tubulo-glomerular feedback and its significance). 2  Basic mechanisms of urine formation: Glomerular capillaries Bowman’s space Peritubular capillaries Manipal University College Malaysia 3  Glomerular Membrane Manipal University College Malaysia 4 Glomerular Membrane 5 Glomerular Capillary Membrane Outer surface of the glomerulus Epithelial lining of Bowman’s capsule (podocytes) Middle layer (basement membrane) Strong negative charges Fenestrated endothelial cell lining 6  Glomerular filtration rate (GFR) Glomerular filtration rate is the volume of plasma filtered by all nephrons of both kidneys per unit time The GFR in a healthy adult is approximately ‘125 mL/min’ i.e. 7.5L/h, or 180 L/d In a day the kidneys filter an amount of fluid equal to 60 times the plasma volume! Normal urine volume is about 1 L/d, it means that 99% of the filtrate is normally reabsorbed. Manipal University College Malaysia 7  Filtration fraction Filtration fraction is the fraction of the renal plasma flow that is filtered (The ratio of the GFR to the RPF) Glomerular filtration rate Filtration fraction = Renal plasma flow Filtration fraction, is normally 0.16 to 0.20 This means that about 16% - 20% of the plasma flowing through the kidney is filtered through the glomerular capillaries Manipal University College Malaysia 8  Filtration fraction E.g. Glomerular filtration rate = 125ml/min Renal plasma flow = 625ml/min Filtration fraction = 125ml/min 625ml/min = 0.2 or 20% Manipal University College Malaysia 9  Factors determining the glomerular filtration Governed by 2 major factors 1. Filtration coefficient Capillary permeability Size of capillary bed (Surface area) 2. Pressure gradient /Starling forces (hydrostatic and osmotic pressure gradients) 10  Factors determining the glomerular filtration (Starling’s forces) Manipal University College Malaysia 11  Factors determining the glomerular filtration Forces Favoring Filtration: PGC: Glomerular capillary hydrostatic pressure (60 mmHg) πBS : Bowman’s capsule oncotic pressure (0 mmHg) Forces Opposing Filtration PBS : Bowman’s capsule hydrostatic pressure (18 mm Hg) πGC :Glomerular capillary oncotic pressure (32 mmHg) Manipal University College Malaysia 12  Effective filtration pressure Effective filtration pressure (net filtration pressure) is the sum of the hydrostatic and colloid osmotic forces across the glomerular membrane Effective filtration pressure = PGC – PBS – πGC + πBS = 60 – 18 – 32 + 0 = 10 mm Hg GFR = Kf x Effective filtration pressure Kf = Glomerular filtration rate Effective filtration pressure Manipal University College Malaysia 13  Effective filtration pressure GFR = Kf [(PGC – PBS) – (πGC – πBS)] Kf : the glomerular ultrafiltration coefficient, is the product of the permeability of glomerular capillary wall and the effective filtration surface area PGC : the mean hydrostatic pressure in the glomerular capillaries PBS : the mean hydrostatic pressure in the Bowman’s space πGC : the oncotic pressure of the plasma in the glomerular capillaries πBS : the oncotic pressure of the filtrate in the Bowman’s space Manipal University College Malaysia 14  Factors affecting the GFR Changes in renal blood flow Changes in glomerular capillary hydrostatic pressure Afferent or efferent arteriolar constriction/dilation Changes in hydrostatic pressure in Bowman’s capsule Filtration coefficient Glomerular capillary oncotic pressure. Size, shape and electrical charges of the macromolecules. Manipal University College Malaysia 15  Factors that affect GFR by altering the glomerular capillary hydrostatic pressure (PGC ): ↓blood flow −−→ ↓PGC −−→ ↓GFR If mean systemic arterial pressure drops below the autoregulatory range −−→ ↓PGC −−→ GFR drops sharply. Afferent arteriolar constriction−−→ ↓PGC −−→ ↓GFR Efferent arteriolar constriction −−→ ↑PGC −−→ ↑GFR Efferent arteriolar dilation −−→ ↓PGC −−→ ↓GFR Afferent arteriolar dilation −−→↑PGC −−→ ↑GFR Manipal University College Malaysia 16 Factors that affect GFR by altering the glomerular capillary hydrostatic pressure (PGC ): 17 Factors that affect GFR by altering the hydrostatic pressure in Bowman’s space (PBS): Ureteral obstruction −−→ fluid accumulates in the kidney −−→ ↑PBS −−→ ↓GFR Edema of kidney inside renal capsule−−→increase in renal interstitial pressure −−→ ↑PBS−−→ ↓GFR Manipal University College Malaysia 18  Factors that affect GFR by altering the glomerular capillary oncotic pressure (πGC ): Variations in the concentration of plasma proteins can alter the GFR) (inverse relationship) Dehydration −→ ↑[plasma protein] −→ ↑πGC −−→ ↓GFR Hypoproteinemia −−→ ↓[plasma protein] −−→ ↓πGC −−→ ↑ GFR (the protein loss in urine caused by some renal diseases can also lead to a decrease in the plasma protein concentration and thus in πGC) Manipal University College Malaysia 19  Factors that affect GFR by altering the glomerular filtration coefficient (Kf): Changes in glomerular capillary permeability Changes in effective filtration surface area Renal disease, diabetes mellitus & chronic hypertension gradually reduce Kf by increasing the thickness of the basement membrane and by damaging the capillaries Contraction of mesangial cells produce a decrease in Kf by decreasing the surface area available for filtration (Angiotensin II is an important regulator of mesangial contraction) Manipal University College Malaysia 20  Factors that affect GFR by altering the glomerular filtration coefficient (Kf): Manipal University College Malaysia 21  Tubuloglomerular feedback It is a feedback regulatory mechanism that responds to changes in [NaCl] in tubular fluid and regulate the glomerular filtration Macula densa cells of JG apparatus sense the variation in the Na+&Cl– level and control the afferent arteriolar resistance, and in turn GFR Manipal University College Malaysia 22  Tubuloglomerular feedback  BP  RBF &  GFR  Filtered fluid load enters the distal tubule  Con. & Absorption of NaCl at MD Release of Adenosine (A2 Receptors) And endothelins and  renin AA - Constriction & Contraction of Mesangial Cells Manipal University College Malaysia RBF & GFR Restored Myogenic regulation of renal blood flow and GFR  BP  RBF &  GFR  Perfusion Pressure Stretch of smooth muscles Constriction of Afferent Arteriole RBF & GFR Restored  Significance of autoregulation It maintain the constancy of the load delivered to the distal tubule Maintains the constant delivery of Na+&Cl– to the distal tubule and helps prevent fluctuations in renal excretion. In many circumstances, this feedback regulates renal blood flow and GFR in parallel. Even when mean arterial pressure changes (between 80 mm Hg to 180 mm Hg) the excretion of both solute and fluid is unaltered. Manipal University College Malaysia 25  Disclaimer The figures, flowcharts used in the presentation are not my own. They are taken from the prescribed textbooks, Internet and Dr Harini’s slides. Students are advised to read textbooks for better understanding. Manipal University College Malaysia 27  THANK YOU THANK YOU