RENAL SYSTEM PHYSIOLOGY Dr Shahab Shaikh PhD, MD Lecture – 2: Glomerular Filtration •••••••••••••••••••••••••••••••••• College of Medicine Al Maarefa Colleges of Science & Technology

OBJECTIVES Identify three basic processes involved in urine formation. Define GFR and quote normal value Describe the composition of the glomerular filtrate Detect the structural & functional peculiarities of the glomerular filtration membrane Outline the factors controlling GFR Understand the concept of 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.

Urine Formation Three Basic Mechanisms (Renal Processes) of Urine Formation include: Glomerular filtration - GF Tubular reabsorption - TR Tubular secretion - TS

Urine Formation Renal Handling of different substances during Urine Formation: Urine Substance X Substance Y Substance Z Substance W W: filtered & secreted, but not reabsorbed (e.g. H+ ions) X : filtered & partially reabsorbed ( e.g. Urea, Na+ etc.) Y : filtered & completely reabsorbed (e.g. Glucose) Z :filtered but neither reabsorbed nor secreted (e.g. Creatinine)

Glomerular Filtration The first step in urine formation is the Glomerular filtration during which, large quantity of water and solutes pass through the filtration membrane from the blood into the Bowman’s Capsule due to pressure gradient. The glomerular capillaries are relatively impermeable to plasma proteins, so the filtered fluid (glomerular filtrate) is free from : Blood cells Protein Protein-bound molecules (calcium, fatty aids, amino acids) The glomerular filtrate contains crystalloids in virtually the same concentrations as in the plasma.

Glomerular Filtration Thus essentially the composition of Glomerular filtrate is similar to plasma (except Plasma Proteins) and consists of: Water Electrolytes Glucose, Amino Acids Urea Creatinine Uric Acid Urobilinogen etc.

Glomerular Filtration Proteinuria: means the presence of an excess of serum proteins in the urine. An increase in the level of urine albumin between 30–300 mg/24 hours is called as Microalbuminuria Value higher than 300mg/24 hours is called as Macroalbuminuria. Clinical Significance of Proteinuria: Early detection of renal disease in at-risk patients Hypertension: Hypertensive Renal Disease Diabetes: Diabetic Nephropathy Pregnancy: Pre-eclampsia Assessment and monitoring of known renal disease

Glomerular Filtration Glomerular Filtration Rate (GFR): Definition: It is the Volume of plasma filtered by all nephrons of both kidneys per unit time. Normal GFR = 125ml/min or 180L/day. Determined By: Sum of the hydrostatic and colloid osmotic pressures across the glomerular membrane, called the NET FILTRATION PRESSURE. The Capillary Filtration Coefficient (Kf) Thus GFR = Kf x Net Filtration Pressure

Glomerular Filtration Filtration coefficient (Kf): “Surface Area” available for filtration and “Membrane Permeability” determine Filtration Coefficient (Kf). The normal Membrane Permeability of glomerular capillaries is very high as compared to other capillaries in body. Normally it is not highly variable. Disease that can reduce Kf and thus GFR are: chronic hypertension obesity / diabetes mellitus glomerulonephritis

Glomerular Filtration Net filtration Pressure: The net filtration pressure is the sum of the hydrostatic and colloid osmotic pressures that either favor or oppose filtration across the filtration membrane. These pressures are: Glomerular hydrostatic pressure (PG) Glomerular colloid osmotic pressure (πG) Bowman’s capsular hydrostatic pressure (PB) Bowman’s capsular colloid osmotic pressure (π B). It is approximately 10 mmHg

Glomerular Filtration Net filtration Pressure: 10mmHg Forces Favoring filtration Glomerular hydrostatic pressure PG = 60 mmHg Due to high renal blood supply and high efferent arteriolar resistance Bowman’s capsular colloid osmotic pressure πB = 0 mmHg Due to absence of proteins in the Bowman’s capsular space Forces Opposing filtration Bowman’s capsular hydrostatic pressure PB = 18 mmHg Due to filtered fluid in the Bowman’s capsule Glomerular colloid osmotic pressure πG = 32mmHg Due to the osmotic pressure exerted by the plasma proteins. Note: the values here are from Guytons Textbook. Different books may mention slightly different values.

Glomerular Filtration Net filtration Pressure:

Being Curious … Can you think of some situations where there may occur Increase/Decrease in following Pressures and what might be the effect? Glomerular hydrostatic pressure (PG) Bowman’s capsular colloid osmotic pressure (πB) Bowman’s capsular hydrostatic pres sure (PB) Glomerular colloid osmotic pressure (πG)

Glomerular Filtration Factors affecting GFR: Changes in renal blood flow Changes in glomerular capillary hydrostatic pressure Changes in systemic blood pressure Afferent or efferent arteriolar resistance Changes in hydrostatic pressure in Bowman’s capsule Ureteral obstruction Edema of kidney inside tight renal capsule Changes in concentration of plasma proteins: Dehydration Hypoproteinemia, etc. Changes in Kf Changes in glomerular capillary permeability Changes in effective filtration surface area

Glomerular Filtration Glomerular Capillary Hydrostatic Pressure (PG): It is the primary means for physiologic regulation of GFR. Increase PG  raises GFR, and vice versa. It is determined by three variables: Arterial Pressure Afferent Arteriolar Resistance Efferent Arteriolar Resistance.

Glomerular Filtration Regulation of GFR: Glomerular capillary hydrostatic pressure can be controlled to adjust GFR to suit body’s needs Two major control mechanisms Extrinsic control by adjusting the constriction of afferent/efferent arterioles Mediated by sympathetic nervous system input to arterioles Baroreceptor reflex Autoregulation Myogenic mechanism Tubuloglomerular feedback (TGF)

Glomerular Filtration Effect of Afferent and Efferent Arteriolar Constriction on Glomerular Pressure: Re PG GFR Ra Ra GFR + Renal Blood Flow Blood Flow Re GFR + Renal

Glomerular Filtration Autoregulation of GFR: Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow and GFR relatively constant, despite marked changes in arterial blood pressure. Autoregulation involves two mechanisms: Tubuloglomerular Feedback Mechanism Myogenic Mechanism

Glomerular Filtration TubuloGlomerular Feedback: GFR Distal NaCl Delivery Macula Densa NaCl Reabsorption Afferent Arteriolar Resistance GFR (return toward normal)

Glomerular Filtration Myogenic Mechanism: Stretch of Blood Vessel Cell Ca++ Permeability Arterial Pressure Intracell. Ca++ Blood Flow Vascular Resistance

Glomerular Filtration Filtration Fraction (FF) : Filtration Fraction is the ratio of the GFR to the renal plasma flow (GFR/TRPF). Renal blood flow is 20-25% of total cardiac output. Thus it is approximately = 1.1 L/min Thus of the 625 ml of plasma which enters the glomeruli via the afferent every minute, 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

Glomerular Filtration Measurement of GFR: Characteristic of substance used for measurement: Freely filtered (not reabsorbed and not secreted) Not metabolized by the kidney Not toxic and stable Not bound to plasma protein Does not change renal plasma flow The substance used to measure GFR is Inulin, a polysaccharide.

References Human physiology by Lauralee Sherwood, 8th edition Text Book Of Physiology by Guyton & Hall, 11th edition Review of Medical Physiology by Ganong. 24th edition

THANK YOU