NOTES NOTES WATER REGULATION OSMOREGULATION osms.it/osmoregulation ▪ Regulation of body ﬂuid solute concentrations ▫ Concentrations measured in osmolarity (mOsm/L) ▫ Osmole: single ion in solution BLOOD PLASMA OSMOLARITY ▪ 290–300 mOsm/L ▪ Main components ▫ Sodium, glucose, urea ▪ Osmolarity = 2[Na+] + [Glucose]/18 + [BUN]/2.8 ▫ Glucose, blood urea nitrogen (BUN) measured in mg/dL HYDRATION ▪ Changes in hydration affect plasma osmolarity, blood pressure ▫ Osmoreceptors in supraoptic nuclei of anterior hypothalamus detect changes in plasma osmolarity ▫ Baroreceptors in cardiovascular system detect changes in blood pressure ▪ Osmoreceptors, baroreceptors regulate production of ADH in hypothalamus Figure 63.1 Body response to overhydration. Overhydration ▪ Plasma osmolarity decreases, blood pressure increases ▪ Osmoreceptors, baroreceptors ﬁre less, stimulating less ADH production ▪ Less/no water reabsorbed from kidneys Dehydration ▪ Plasma osmolarity increases, blood pressure decreases ▪ Osmoreceptors, baroreceptors ﬁre more, stimulating greater ADH production ▪ More water reabsorbed from kidneys 548 OSMOSIS.ORG Figure 63.2 Body response to dehydration.
Chapter 63 Renal Physiology: Water Regulation KIDNEY COUNTERCURRENT MULTIPLICATION osms.it/kidney-countercurrent-multiplication ▪ Concentration gradient (corticopapillary gradient) established in medulla of kidney TWO STEPS ▪ In nephron loop of Henle Single effect ▪ Takes advantage of ascending limb being impermeable to water ▪ Sodium, potassium, chloride ions enter tubule cells along ascending limb via Na+K+2Cl- cotransporters on apical surface ▪ Na/K ATPase pumps sodium ions through basolateral surface into interstitium in exchange for potassium ions ▪ Potassium, chloride ions enter interstitium ▪ Osmosis → ions in interstitium diffuse into descending limb → ﬂuid concentration Flow of ﬂuid ▪ Uses new ﬂuid to distribute ions ▪ New ﬂuid pushes existing ﬂuid around loop ▪ Concentrated ﬂuid (previously in descending limb) enters ascending limb ▪ Single effect recurs, ﬂuid more concentrated at bottom of ascending limb → more ions enter interstitium at bottom Two steps repeat ▪ Form concentration gradient of 1200mOsm/L at inner medulla, 300mOsm/L at outer cortex COUNTERCURRENT EXCHANGE ▪ Important process for corticopapillary gradient ▪ Peritubular capillaries permeable to water, solutes ▪ Osmosis would destroy corticopapillary gradient if capillaries only ran along descending limb → peritubular capillaries run down descending limb, up ascending limb → allow extra solutes pulled from interstitium near descending limb to return to interstitium near ascending limb (as corticopapillary gradient decreases) → water diffused from capillary into interstitium returns Figure 63.3 To increase urine osmolarity, nephrons rely on the corticopapillary gradient. The interstitium becomes increasingly hypertonic relative to the lumen of the tubule. OSMOSIS.ORG 549
Figure 63.4 Single effect: ions leave ascending limb, but water can’t follow → urine osmolarity in ascending limb decreases. Water can pass through descending limb → descending limb equilibrates with the interstitium. Numeric values = number of mOsm/L (e.g. 300 = 300mOsm/L). 550 OSMOSIS.ORG
Chapter 63 Renal Physiology: Water Regulation Figure 63.5 Flow of new ﬂuid into the loop of Henle + single effect = corticopapillary gradient. Numeric values = number of mOsm/L (e.g. 300 = 300mOsm/L). OSMOSIS.ORG 551
Figure 63.6 Countercurrent exchange: peritubular capillaries run down the descending limb and up the ascending limb to maintain the corticopapillary gradient. ANTIDIURETIC HORMONE osms.it/antidiuretic-hormone ▪ Peptide hormone prevents excessive urine production by reabsorbing water from kidneys ▪ Allows body to control amount of ﬂuid retention ▪ Antidiuretic hormone (ADH) production triggered by osmoreceptors in supraoptic nuclei of anterior hypothalamus, baroreceptors in cardiovascular system; stimulated by angiotensin II ▪ ADH (AKA vasopressin) also causes smooth muscles cells in arteries to constrict ADH PATHWAY ▪ Produced in paraventricular, supraoptic neurons of hypothalamus → travels down axons through infundibulum → stored in posterior pituitary gland ▪ When needed, released into blood, travels to kidneys ▪ In kidneys, travels through peritubular 552 OSMOSIS.ORG capillaries → binds to V2 receptors (AVPR2) on basolateral membrane of principal cells (along collecting ducts of nephrons) ▪ AVPR2 signals adenylyl cyclase to convert ATP to cAMP → cell produces water protein channels called aquaporins, opens existing aquaporins (in apical membrane) of principal cells → osmosis pulls water from lumen of ducts into interstitium, reabsorbed into circulation
Chapter 63 Renal Physiology: Water Regulation Figure 63.7 The ADH pathway. Increased plasma osmolarity triggers ADH release from the posterior pituitary. ADH acts on the principal cells of the distal convoluted tubule, collecting ducts → ↑ aquaporins in the cell membranes → ↑ water reabsorption → ↓ plasma osmolarity. OSMOSIS.ORG 553
Figure 63.8 ADH is produced in the paraventricular and supraoptic nuclei in the hypothalamus, stored in Herring bodies in paraventricular and supraoptic neurons, and released into the bloodstream from the posterior pituitary gland. FREE WATER CLEARANCE osms.it/free-water-clearance ▪ Free water: water without solutes ▪ Free water clearance: rate at which kidneys ﬁlter free water out of blood plasma PATHWAY ▪ Free water ﬁltered out of blood plasma in ascending limbs, distal convoluted tubules of kidneys’ nephrons, solutes removed ▪ Free water reabsorbed into circulation through aquaporin protein channels in collecting ducts 554 OSMOSIS.ORG ANTIDIURETIC HORMONE EFFECTS ▪ High amounts of ADH → lots of free water reabsorbed, retained (negative free water clearance) → hyperosmotic urine ▪ Low amounts of ADH → little free water reabsorbed, excreted (positive free water clearance) → hypoosmotic urine ▪ Free water clearance, 0: excreted urine has same osmolarity as blood plasma ▪ CH2O = V - (Uosm/Posm)V ▫ V: urine ﬂow rate (mL/min) ▫ Uosm: urine osmolarity ▫ Posm: plasma osmolarity