Glomerular Filtration URINE FORMATION Nov-18 Glomerular Filtration

Glomerular Filtration Urine formation Urine formation include glomerular filtration tubular reabsoption tubular secretion Urinary excretion of substance is the sum of these 3 renal processes. Nov-18 Glomerular Filtration

Glomerular Filtration Urine formation Urine formation begins with ultrafiltration from glomerular capillaries into Bowman’s capsule Most substances in the plasma except protein are freely filtered Nov-18 Glomerular Filtration

Glomerular Filtration Urine formation Ultrafiltration refers to the passive movement of an essentially protein free fluid from the glomerular capillaries into Bowman’s capsule Nov-18 Glomerular Filtration

Glomerular Filtration Urine formation As filtrate leaves capsule and passes through renal tubules it is modified By reabsorption of water and specific solutes by secretion of other substances from peritubular capillaries into the tubules Nov-18 Glomerular Filtration

Glomerular Filtration Urine formation In general tubular reabsorption is quantitatively more important than tubular secretion but secretion plays important role in determining amount of K+ and H+ and few other substances that are excreted in the urine Substances that must be cleared from the blood especially the end products of metabolism are poorly reabsorbed. Nov-18 Glomerular Filtration

Glomerular Filtration Urine formation Electrolytes Na+,K+, Cl-,HCO3-, Ca2+ are highly reabsorbed Nutritional substance eg glucose, AA, are completely reabsorbed Each of the process filtration, reabsoption, secretion is regulated according to the needs of the body. Nov-18 Glomerular Filtration

Glomerular filtration 1st step in urine formation large amount of fluid is filtered through glomerular capillaries into Bowman’s capsule glomerular capillaries are relatively impermeable to proteins so that the glomerular filtrate is protein free concentration of other plasma constituents including salt and organic molecules that are not bound to plasma proteins are similar in plasma and glomerular filtrate Nov-18 Glomerular Filtration

Glomerular filtration Nov-18 Glomerular Filtration

Glomerular filtration rate (GFR) determined by starling forces capillary filtration coefficient ( kf ) Kf = permeability x filtering surface area of the capillaries Glomerular capillaries have large kf and high glomerular hydrostatic pressure thus high GFR. Nov-18 Glomerular Filtration

Glomerular filtration rate (GFR) GFR ≈ 125ml/min or 180 liters/day GFR ≈15 - 20% renal plasma flow. Nov-18 Glomerular Filtration

Glomerular Filtration Filtration fraction Not all of the plasma entering the kidney and therefore the glomerulus is filtered The portion of plasma that is filtered is termed filtration fraction Filtration fraction = GFR/RPF Nov-18 Glomerular Filtration

Glomerular filtration rate (GFR) Rate of filtration of solutes is determined by molecular size electrical charges. Nov-18 Glomerular Filtration

Glomerular Filtration GFR Substance Mwt Filterability water 18 1.0 Na+ 23 Glucose 180 Inulin 5,500 Myoglobin 17,000 0.75 Albumin 69,000 0.005 Nov-18 Glomerular Filtration

Glomerular Filtration GFR Negatively charged large molecules are filtered less easily than positively charged molecules of equal molecular size. Molecular diameter of Albumin is only ≈ 6nm where as the glomerular membrane pores are thought to be ≈ 8nm Nov-18 Glomerular Filtration

Glomerular Filtration GFR Albumin is restricted from filtration however because of its negative charges the electrostatic repulsion exerted by negative charges of the basement membrane poteoglycan. Nov-18 Glomerular Filtration

Glomerular Filtration Determinants of GFR The sum of starling forces gives net filtration pressure GFR = Kf ⅹ( net filtration pressure) Nov-18 Glomerular Filtration

Glomerular Filtration Determinants of GFR Glomerular capillary hydrostatic pressure (≈ 60mmHg) promotes filtration Bowman’s capsule hydrostatic pressure (≈ 18mmHg) Oppose filtration Nov-18 Glomerular Filtration

Glomerular Filtration Determinants of GFR Glomerular capillary oncotic pressure ( ≈ 32mmHg) Oppose filtration Glomerular filtrate oncotic pressure ( ≈ zero) Promote filtration Net filtration pressure = 10mmHg Nov-18 Glomerular Filtration

Glomerular capillary filtration coefficient (Kf ) can not be measured directly estimated experimentally by GFR/net filtration pressure = 125ml/min/10mmHg =12.5ml/min/mmHg Nov-18 Glomerular Filtration

Glomerular capillary filtration coefficient (Kf ) Increased Kf leads to increased GFR and decrease in Kf reduces GFR Some diseases lower Kf by reducing number of functional glomerular capillaries reducing surface area Nov-18 Glomerular Filtration

Glomerular capillary filtration coefficient (Kf ) OR by increasing thickness of glomerular capillary membrane and reducing its permeability eg chronic uncontrolled hypertension, DM Nov-18 Glomerular Filtration

Glomerular capillary hydrostatic pressure GFR determined by arterial pressure Afferent arteriole resistance Efferent arteriole resistance Nov-18 Glomerular Filtration

Glomerular capillary hydrostatic pressure Constriction of afferent arterioles always reduces GFR However the effect of efferent arteriolar constriction depends on the severity of constriction Nov-18 Glomerular Filtration

Glomerular capillary hydrostatic pressure Modest efferent constriction raises GFR but severe efferent constriction (more than 3 fold increase in resistance) tends to reduce GFR Nov-18 Glomerular Filtration

Glomerular capillary colloid osmotic pressure  Glomerular capillary oncotic pressure  GFR Influenced by the arterial plasma colloid osmotic pressure (p ) and fraction of plasma filtered by the glomerular capillaries (filtration fraction) Increased p leads to an increase in gc which in turn reduces GFR Nov-18 Glomerular Filtration

Glomerular capillary colloid osmotic pressure Increase in the filtration fraction concentrates the plasma proteins and raises the gc Filtration fraction can be increased either by an increased GFR or reduced RBF Nov-18 Glomerular Filtration

Glomerular capillary colloid osmotic pressure Even with a constant glomerular hydrostatic pressure a greater rate of RBF into the glomerulus tends to increase GFR and a lower rate of RBF into the glomerulus tends to reduce GFR Nov-18 Glomerular Filtration

Bowman’s capsule hydrostatic pressure  Bowman’s capsule hydrostatics pressure GFR increased by obstruction of urinary tract eg precipitation of calcium, uric acid Nov-18 Glomerular Filtration

Physiological control of GFR and renal blood flow The determinants of GFR that are most variable and subject to physiological control include the glomerular hydrostatic pressure and glomerular capillary colloid osmotic pressure Nov-18 Glomerular Filtration

Physiological control of GFR and renal blood flow These variables in turn are influenced by sympathetic nervous system hormones and autacoids and other feedback control that are intrinsic to the kidney Nov-18 Glomerular Filtration

Sympathetic nervous system SNS activation decreases GFR strong activation of renal sympathetic nerves constrict renal arterioles decrease renal blood flow decrease GFR Nov-18 Glomerular Filtration

Sympathetic nervous system moderate or mild stimulation has little influence on renal blood flow and GFR renal sympathetic nerves seem to be most important in reducing GFR during severe, acute disturbances lasting for few min to few hours. Nov-18 Glomerular Filtration

Hormones and autacoids Noradrenaline and adrenaline constrict afferent and efferent arterioles causing reduction in GFR. Angiotensin II constricts efferent arterioles raise glomerular hydrostatic pressure reduce renal blood flow Nov-18 Glomerular Filtration

Hormones and autacoids Angiotensin II associated with decreased or volume depletion helps to prevent decreases in glomerular hydrostatics pressure and GFR. Nov-18 Glomerular Filtration

Hormones and autacoids Endothelial derived NO decrease renal vascular resistance and increases GFR basal level of NO prevent excessive vasoconstriction of the kidneys and allowing them to excrete normal amounts of Na+ and water. Nov-18 Glomerular Filtration

Hormones and autacoids PGE2,PGI2 and bradykinin increase renal blood flow and GFR Not of major importance in regulating renal blood flow or GFR in normal conditions Nov-18 Glomerular Filtration

Autoregulation of GFR and RBF Feedback mechanism intrinsic to the kidneys keeps the renal blood and GFR relatively constant despite marked changes in BP Nov-18 Glomerular Filtration

Autoregulation of GFR and RBF The major function of autoregulation in the kidney is to maintain a relatively constant GFR allow precise control of renal excretion of water and solutes. Changes of BP 80 –170mmHg cause only slight changes in GFR Nov-18 Glomerular Filtration

Autoregulation of GFR and RBF The mechanisms are not 100% perfect but prevent potentially large changes in GFR and renal excretion of water and solutes that would otherwise occur with changes in BP Changes in BP exert much less of an effect on urine volume Autoregulation glomerulotubular balance tubuloglomerular feedback Nov-18 Glomerular Filtration

Tubuloglomerular feedback mechanism links changes in [NaCl] at the macula densa with the control of renal arteriolar resistance Helps to ensure relatively constant delivery of NaCl to the distal tubule and helps to prevent great fluctuations in renal excretion Nov-18 Glomerular Filtration

Tubuloglomerular feedback In many circumstances this feedback autoregulates renal blood flow and GFR in parallel. The feedback mechanism has 2 components that work together to control GFR. Afferent arteriolar feedback mechanism. Efferent arteriolar feedback mechanism. Nov-18 Glomerular Filtration

Tubuloglomerular feedback They depend on special anatomical arrangements of the juxtaglomerular complex. Decreased macula densa NaCl causes dilatation of afferent arterioles and increased rennin release.  GFR  Na reabsoption Nov-18 Glomerular Filtration

Tubuloglomerular feedback BP Glomerular hydrostatic pressure GFR   Rennin Macula densa NaCl  Angiotensin II Efferent arteriolar resistance Afferent arteriolar resistance Nov-18 Glomerular Filtration

Glomerolotubular balance is adaptive mechanism in the renal tubules which allow them to increase their reabsoption rate when GFR rise The tubules increase reabsoption rate in response to increased tubular load Nov-18 Glomerular Filtration

Glomerulotubular balance For example if GFR is increased from 125 to 150ml/nim, the absolute rate of proximal tubular reabsorption also increases from about 81 to 97.5ml/min. The total rate of reabsorption increases as the filtered load increases even though the % of GFR reabsorbed remains relatively constant . Nov-18 Glomerular Filtration

Glomerolotubular balance Some degree of glomerulotubular balance also occur in other tubular segments especially loop of Henle Can occur independent of hormones Help to prevent overloading of distal tubules when GFR increases. Nov-18 Glomerular Filtration

Myogenic autoregulation of GFR&RBF Ability of individual blood vessels to resist stretching during increased arterial pressure. Helps to prevent excessive increases in renal blood flow and GFR when arterial pressure increases. Nov-18 Glomerular Filtration

Physiological control of GFR&RBF High protein intake and increased blood glucose increase RBF and GFR Nov-18 Glomerular Filtration