8131MED - Renal Physiology _ Part 4 (GFR regulation and fluid homeostasis).pdf

GFR regulation and fluid homeostasis Dr. Nicole Flemming – [email protected] Learning Objectives 1. Briefly describe the role of the kidney in the regulation of fluid homeostasis in the body, including the renin-angiotensin aldosterone system. Define GFR Amount of filtrate produced per minu...

GFR regulation and fluid homeostasis Dr. Nicole Flemming – [email protected] Learning Objectives 1. Briefly describe the role of the kidney in the regulation of fluid homeostasis in the body, including the renin-angiotensin aldosterone system. Define GFR Amount of filtrate produced per minute ~125 mL per minute ~180 L filtrate per day RENAL FN. Any factor that influences net filtration pressure GFR Blood pressure Blood volume Various disease Integrity of the filtration membrane….. Glomerular daily changes exercise, coffee.. intrinsic and extrinsic both kidneys affected - death in days need to regulate Under physiological conditions, BCOP and CsHP do not vary greatly Hydrostatic pressure is more susceptible to change Glomerular surface area Permeability of glomerular membrane Regulation of GFR There are 3 interacting levels of control that work together that ensure GFR is maintained within homeostatic limits. Neural regulation Autoregulation Hormonal regulation Neural regulation of GFR Sympathetic division of ANS Sympathetic activation produces strong vasoconstriction of afferent arterioles Stimulate renin release from juxtaglomerular cells Activation of these pathways can therefore: Decreases renal blood flow Decreases GFR Decreases amount of filtrate produced at gloms Decreases urine compensate for drop in blood pressure This mechanism can ‘override’ local regulatory mechanisms in the kidney during an extreme disturbance to blood pressure Image created with BioRender Autoregulation of GFR (tubuloglomerular feedback) Juxtaglomerular complex is made up of three main cell types where distal tubule extends back to glomerulus vasoconstrict less blood flow Mesangial cells decrease in hydrostatic pressure Between afferent and efferent arterioles Feedback between macula densa and juxtaglomerular cells move along nephron tubule Macula densa Tall, closely packed epithelial cells Chemoreceptors/baroreceptors Na+ Cldecreased sodium and chloride can decrease resistance increase renin - constrict efferent arteriole to increase GFR Juxtaglomerular cells (granular cells) Modified smooth muscle cells @ wall of the afferent arteriole Baroreceptors → monitor blood pressure in the afferent arteriole Secrete renin… acts via RAAS Decrease GFR - More time to reabsorb decrease delivery to macula densa Image created with BioRender decrease hydrostatic pressure and decrease filtration concentration of sodium and chloride in tubular filtrate slows flow cause release of vasoconstrictor chemicals sense ions Hormonal regulation of GFR Renin-angiotensin-aldosterone system (RAAS) converts to ANG-I Release due to decrease in blood pressure from lung capillaries BY ACE release Image created with BioRender Anti-diuretic hormone (vasopressin) Synthesis Produced by neurons in the hypothalamus, transported by axons to the posterior pituitary Stimulus promote reabsorption of water Osmoreceptors in hypothalamus sense increased osmolarity Large decrease in BV due to reduced stimulation of stretch receptors promote vasopressin stimulate aquaporins Mechanism of action ADH - to cells of collecting duct move into hyperosmotic fluid Inserts aquaporins into DCT/CD → increase water permeability Water moves from tubule into hyperosmotic interstitial fluid and into peritubular capillaries → circulatory system Normalise plasma osmolarity and blood volume Aldosterone Synthesis Synthesised in the Zona glomerulosa of the adrenal cortex Stimulus Increased plasma K+ Decreased plasma Na+ stimulate aldosterone Mechanism of action Aldosterone binds to membrane receptor Stimulates Na+ and Cl- retention in the kidney Indirectly promotes water retention ADH - directly promotes reabsorption following salt Atrial natriuretic peptide Synthesis Atria of the heart Stimulus blood volume increase too quickly promote filtration rate Atrial stretch due to increased blood volume / venous return to heart increase in volume - increase GFR, more fluid loss Mechanism of action Vasodilation of afferent arteriole + vasoconstriction of efferent arteriole Promotes Na+ and water excretion by the kidney Increase urine production, decreased blood volume and pressure Inhibits ADH secretion via AMP decrease blood volume and pressure less reabsorption - more urine production increase GFR