Anatomy and Physiology Part 3: Urine Formation, GFR, Control of GFR Marieb’s Human Anatomy and Physiology Ninth Edition Marieb w Hoehn Chapter 25 Urinary system Lecture 15 Part 3: Urine Formation, GFR, Control of GFR Slides 1-15; 80 min (with review of syllabus and Web sites) [Lecture 1] Slides 16 – 38; 50 min [Lecture 2] 118 min (38 slides plus review of course Web sites and syllabus)

Glomerular Filtration Rate (GFR) NFP = HPg – (HPc + OPg) Net Filtration Pressure = force favoring filtration – forces opposing filtration (*glomerular capillary ( capsular hydrostatic pressure hydrostatic pressure) + glomerular capillary osmotic pressure ) Net filtration pressure is normally positive, i.e., favors the movement of fluid out of the glomerular capillaries Figure from: Hole’s Human A&P, 12th edition, 2010 GFR = amount of filtrate produced each minute (~125 ml/min)

Glomerular Filtration Rate (GFR) Net filtration pressure, although normally positive, is relatively low ( 10 mm Hg) Glomerular hydrostatic pressure is the blood pressure in the glomerular capillaries, and is usually higher than the other systemic capillary pressures Capsular hydrostatic pressure tends to push water and filtrate BACK into the capillaries Anything that alters the filtration pressures will alter GFR * Blood pressure is the most important factor altering the glomerular hydrostatic pressure (and NFP). A MAP fall of 10% at the glomerulus will severely impair glomerular filtration; a fall of 15-20% will stop it.

Amounts of Glomerular Filtrate and Urine Glomerular Filtration Rate (GFR) is directly proportional to the net filtration pressure GFR  125 ml/min (180 L/day) This means that all of the plasma is filtered ~ 60x every day (How did we get this number?) Notice that urine output is only 0.6 – 2.5 L per day (an average of about 1.8 L, or about 1% of glomerular filtrate); 99% of filtrate is reabsorbed!! Figure from: Hole’s Human A&P, 12th edition, 2010 For every 1mm Hg filtration pressure, the kidneys produce about 12.5 ml of filtrate. This is called the filtration coefficient. (Men, ~ 125ml/min, women, ~ 105 ml/min.) average amounts over a 24 hour period

Afferent/Efferent Arterioles – Effect on GFR Innervated by sympathetic nerves Afferent arteriole Δ radius  GFR  radius  GFR;  radius  GFR Efferent arteriole Δ radius  1/GFR  radius  GFR;  radius  GFR

Summary of Factors Affecting GFR Effect Vasoconstriction (↑ Sympathetic stimulation) Afferent arteriole  GFR Efferent arteriole ↑ GFR Vasodilation ( Sympathetic stimulation) Increased capillary hydrostatic pressure Increased colloid osmotic pressure Increased capsular hydrostatic pressure Know this table – it’s important!

Regulation of GFR Autoregulation Maintains GFR despite changes in local blood pressure and blood flow (between 90 – 180 mm Hg mean systemic pressure) Myogenic mechanism – contraction of afferent arteriolar vascular smooth muscle when stretched (increased BP); relaxation occurs when BP declines Tubuloglomerular mechanism – MD cells detect  flow rate and/or  osmolarity of filtrate in DCT -> JG cells contract -> afferent arteriole constricts ->  GFR

Neural (Autonomic) Regulation Regulation of GFR Neural (Autonomic) Regulation Mostly sympathetic postganglionic fibers = vasoconstriction of afferent arterioles  GFR (conserves water, redirects blood to other organs) Stimulates juxtaglomerular apparatus to secrete renin May override autoregulatory mechanism at afferent arteriole Hormonal Regulation Renin-angiotensin system – stabilizes BP and ECF volume Atrial Natriuretic Peptide (ANP) - ↑ GFR, ↑ fluid loss (dilates afferent arteriole, constricts efferent arteriole)

Renin-Angiotensin System Renin is released by the juxtaglomerular apparatus due to: 1) Decline of BP (Renin  1/Pressure) 2) Juxtaglomerular stimulation by sympathethic NS 3) Decline in osmotic concentration of tubular fluid at macula densa ( Renin  1/[NaCl] ) Figure from: Hole’s Human A&P, 12th edition, 2010 (ACE) Renin secretion is inversely proportional to 1) arteriolar pressure and 2) amount of Na+ and Cl- entering the distal tubules. Stabilizes systemic blood pressure and extracellular fluid volume

Review Glomerular filtration Glomerular filtration rate (GFR) Amount of filtrate produced each minute Directly proportional to net filtration pressure May be determined with creatinine or inulin tests Approximately 125 ml/min (180 L/day) Factors affecting GFR Vasoconstriction / vasodilation Capillary hydrostatic pressure Capsular hydrostatic pressure Capillary osmotic pressure

Review Glomerular filtration (cont’d) Factors controlling GFR Autoregulation Myogenic Tubuloglomerular Hormonal Renin-Angiotensin System ANP Autonomic nervous system