Arteriolar Resistance and Renal Plasma Flowx

Arteriolar Resistance and Renal Plasma Flow ′ s Law: 𝐹𝑙𝑜𝑤 = 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒 Ohm 𝑅𝑒𝑠𝑖𝑠𝑡𝑎𝑛𝑐𝑒 Hence, RPF depends on: • • Perfusion pressure Afferent (AA) and efferent arteriole (EA) vascular tone RPF is controlled by: 1. Renal vascular geometry 2. Renal SNS activity 3. Autoregulation a. Myogenic reflex b. Tubuloglomerular feedback (TGF) c. Hormones and local factors 1. Renal Vascular Geometry • Arterial pressure changes from aorta to AA • For detail on renal vasculature, see FoM2 Anatomy Notes 2. Renal SNS Activity • SNS NE fibres  Innervate: o AA/EA: cause vasoconstriction via α1-adrenoreceptors o Juxtaglomerular cells: cause renin release via β-adrenoreceptors o Tubular elements: cause ↑Na+ absorption 3. Autoregulation • Intrinsic mechanisms: o Myogenic reflex o Tubuloglomerular feedback (TGF)  Extrinsic mechanism: o Hormone and local factors o E.g. ATII, ADH, NO, PGs • Extrinsic mechanisms can override intrinsic mechanisms Calculations Net Filtration Pressure (NFP) (𝑝𝐺𝐶 + 𝜋𝐵𝐶) − ((𝑝𝐵𝐶 + 𝜋𝐺𝐶) favouring filtration – opposing filtration Single Nephron GFR (SNGFR) 𝑅𝑓 × 𝑁𝐹𝑃 Rf = Glomerular ultrafiltrate coefficient (SA x Capillary Wall Conductivity) Filtration Fraction 𝐺𝐹𝑅 𝐹𝐹% = × 100 𝑅𝑃𝐹 ~125𝑚𝐿/𝑚𝑖𝑛 𝐹𝐹% = ×100 ~600𝑚𝐿/𝑚𝑖𝑛 = 10 − 15% Renal Clearance 𝑈𝑟𝑖𝑛𝑒 [𝑥] × 𝑈𝑟𝑖𝑛𝑒 𝐹𝑙𝑜𝑤 𝑅𝑎𝑡𝑒 Clearance of 𝑥 = 𝑃𝑙𝑎𝑠𝑚𝑎 [𝑥] 𝐾=𝑈 𝑥 ×𝑉 � � � � Measuring GFR and RPF Case 1: Measuring GFR 𝑃𝑥 × 𝐺𝐹𝑅 Filtered but not secreted or reabsorbed e.g. Inulin, Creatinine Creatinine can be used to estimate GFR because it has a relatively constant production rate, is freely filtered through the glomerulus and is not reabsorbed. Creatinine is, however, slightly secreted, producing a 20% overestimated GFR value 𝑃𝑙𝑎𝑠𝑚𝑎 𝐶𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 = 𝐺𝐹𝑅 𝐴𝑚𝑜𝑢𝑛𝑡 𝐹𝑖𝑙𝑡𝑒𝑟𝑒𝑑 = 𝐴𝑚𝑜𝑢𝑛𝑡 𝐸𝑥𝑐𝑟𝑒𝑡𝑒𝑑 𝑃𝑖𝑛 × 𝐺𝐹𝑅 = 𝑈𝑖𝑛 × 𝑉̇ 𝑈𝑥 × 𝑉̇ 𝑈𝑥 × 𝑉̇ ∴ 𝐺𝐹𝑅 (𝑚𝐿/𝑚𝑖𝑛) = 𝑃𝑥 Case 2: Measuring RPF Filtered and secreted 𝑃𝑎𝑥 × 𝑅𝑃𝐹 e.g. Para-amino hippuric acid (PAH) PAH PAH is partially filtered through the glomerulus. Any that escapes filtration is secreted into the tubule. Hence, all PAH entering the glomerulus is cleared. Fick Principle: 𝐴𝑚𝑜𝑢𝑛𝑡 𝐸𝑛𝑡𝑒𝑟𝑖𝑛𝑔 = 𝐴𝑚𝑜𝑢𝑛𝑡 𝐸𝑥𝑐𝑟𝑒𝑡𝑒𝑑 𝑃𝑣𝑥 × 𝑅𝑃𝐹 𝑃𝑎𝑥 × 𝑅𝑃𝐹 = 𝑈𝑥 × 𝑉̇ + 𝑃𝑣𝑥 × 𝑅𝑃𝐹 𝑈𝑥 × 𝑉̇ But if no substance is remaining in blood vessel, then 𝑃𝑣𝑥 = 0 𝑃𝑎𝑥 × 𝑅𝑃𝐹 = 𝑈𝑥 × 𝑉̇ 𝑈𝑥 × 𝑉̇ 𝑅𝑃𝐹 (𝑚𝐿/𝑚𝑖𝑛) = 𝑃 𝑎𝑥 This is actually “effective RPF” (ERPF) which is 85-90% of the true RPF as 1015% renal arteries supply parts of the kidney that don’t filter PAH Filtration Fraction Filtration fraction is the percentage of RPF that is filtered through the glomerulus (GFR) in a single pass. GFR is found by using inulin and RPF is found using PAH. Filtration fraction then can be expressed as: 𝐺𝐹𝑅 𝐹𝑖𝑙𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛 % = × 100 𝑅𝑃𝐹 See ‘Calculations’ on page 11. Case 3: Glucose Clearance � �𝑥 × 𝐺𝐹𝑅 Filtered and Reabsorbed e.g. Glucose Glucose is minimally filtered through the glomerulus, but any glucose that does pass into the tubular fluid is reabsorbed. Glucose reabsorption is rate limited: 180mg/100mL plasma 𝑈𝑥 × 𝑉̇ 𝑃𝑙𝑎𝑠𝑚𝑎 𝐶𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒 = 𝐺𝐹𝑅 = 𝑃𝑥 But 𝑈𝑥 = 0 because no glucose is excreted in the urine 𝑈𝑥 × 𝑉̇ Note: =Px = [x] in plasma (mmol/L) Ux = [x] in urine (mmol/L) 𝑉̇ = urine flow rate (≈1mL/min) Threshold Maximum (Tm) • Below Tm: all filtered glucose is reabsorbed with spare absorptive capacity • At Tm: all filtered glucose is reabsorbed but there is no spare capacity • Above Tm: the amount of glucose filtered exceeds the absorptive capacity, so the excess filtered glucose is excreted