Fluid and Electrolyte Homeostasis Na+ and water: ECF volume and osmolarity K+: cardiac and muscle function Ca2+: exocytosis, muscle contractions, and other functions H+ and HCO3–: pH balance Body must maintain mass balance Excretion routes: kidney and lungs

Water Balance in the Body 1/2 of body weight is water. Majority is in cells (2/3) Water loss mostly thru kidney. Pathological water loss: Excessive sweating Diarrhea 2 problems: volume depletion lowers BP, if hypoosmotic loss (sweating) increase body osmolarity damaging cells Figure 20-2

Water Balance A model of the role of the kidneys in water balance When body needs to eliminate excess water--diuresis Figure 20-3

Fluid and Electrolyte Homeostasis The body’s integrated response to changes in blood volume and blood pressure Which one is fastest? Figure 20-1a

Fluid and Electrolyte Homeostasis Figure 20-1b

Urine Concentration Osmolarity changes as filtrate flows through the nephron Water is reabsorbed by osmosis--need concentration gradient High osmotic gradient of interstitial fluid in medulla allows urine to be concentrated. Distal tubule and collecting ducts alter their permeability to water via addition or removal of water pores regulated by the posterior pituitary hormone vasopressin=ADH. Figure 20-4

Water Reabsorption Water movement in the collecting duct in the presence and absence of vasopressin Figure 20-5a

Water Reabsorption Figure 20-5b

Water Reabsorption The mechanism of vasopressin action Collecting duct lumen Filtrate 300 mOsm Cross-section of kidney tubule Collecting duct cell Medullary interstitial fluid Vasopressin receptor Vasa recta binds to mem- brane receptor. 1 600 mOsM 700 mOsM Figure 20-6, step 1

Water Reabsorption Figure 20-6, steps 1–2 Collecting duct lumen Filtrate 300 mOsm Cross-section of kidney tubule Collecting duct cell Second messenger signal cAMP Medullary interstitial fluid Vasopressin receptor Vasa recta binds to mem- brane receptor. Receptor activates cAMP second messenger system. 1 2 600 mOsM 700 mOsM Figure 20-6, steps 1–2

Water Reabsorption Figure 20-6, steps 1–3 Collecting duct lumen Filtrate 300 mOsm Exocytosis of vesicles Cross-section of kidney tubule Collecting duct cell Second messenger signal cAMP Storage vesicles Aquaporin-2 water pores Medullary interstitial fluid Vasopressin receptor Vasa recta binds to mem- brane receptor. Receptor activates cAMP second messenger system. Cell inserts AQP2 water pores into apical membrane. 1 2 3 600 mOsM 700 mOsM Figure 20-6, steps 1–3

Water Reabsorption Figure 20-6, steps 1–4 Collecting duct lumen Filtrate 300 mOsm H2O Exocytosis of vesicles Cross-section of kidney tubule Collecting duct cell Second messenger signal cAMP Storage vesicles Aquaporin-2 water pores 600 mOsM Medullary interstitial fluid Vasopressin receptor Vasa recta 700 mOsM binds to mem- brane receptor. Receptor activates cAMP second messenger system. Cell inserts AQP2 water pores into apical membrane. Water is absorbed by osmosis into the blood. 1 2 3 4 Figure 20-6, steps 1–4

Factors Affecting Vasopressin Release Main Trigger Figure 20-7

Water Balance The effect of plasma osmolarity on vasopressin secretion by the posterior pituitary Vasopressin is signal for water reabsorption, but high osmolarity of medullary interstital fluid is the key to forming concentrated urine. Figure 20-8

Countercurrent Heat Exchanger Figure 20-9

Water Balance Countercurrent exchange in the medulla of the kidney Countercurrent multiplier generates hyperosmotic interstitial fluid and hyperosmotic flitrate leaving loop Figure 20-10

Ion reabsorption Active reabsorption of ions in the thick ascending limb creates a dilute filtrate in the lumen “Loop Diuretics” furosemide (Lasix) x Figure 20-11

Fluid and Electrolyte Balance Vasa recta removes water Close anatomical association of the loop of Henle and the vasa recta--“countercurrent exchange” Urea increases the osmolarity of the medullary interstitium--urea is 50% of solutes

Sodium Balance Homeostatic responses to salt ingestion Figure 20-12 Regulation of Na is due to steroid hormone aldosterone Figure 20-12

Sodium Balance Aldosterone action in principle cells Figure 20-13 Interstitial fluid Blood Aldosterone ATP receptor New channels P cell of distal nephron Translation and protein synthesis Proteins modulate existing channels and pumps. New pumps K+ Na+ secreted reabsorbed Lumen of distal tubule combines with a cytoplasmic receptor. Hormone-receptor complex initiates transcription in the nucleus. New protein and pumps are made. Aldosterone- induced proteins modify existing proteins. Result is increased Na+ reabsorption and K+ secretion. 1 2 3 4 5 Transcription mRNA Figure 20-13

Sodium Balance The renin-angiotensin-aldosterone pathway Figure 20-14 Primary stimuli for aldosterone secretion is hyperkalemia (excess K acts on adrenal cortex cells) and decreased blood pressure Decreased blood pressure triggers a complex pathway using another hormone, angiotensin II--the usual signal controlling aldosterone release Granular cells in afferent arteriole juxtaglomerular apparatus stimulated when BP drops Ang II is very powerful hormone that has a strong vasoconstrictive action Major target for antihypertensive drugs--Captopril (ACE inhibitor) Figure 20-14

Sodium Balance Decreased blood pressure stimulates renin secretion Figure 20-15

Sodium Balance Action of natriuretic peptides Figure 20-16 What about hormones that might cause LOSS of Na--natriuresis--and accompanying diuresis Could be useful therapeutic agents for lowering BP and blood volume Atrial Natriuretic peptide (ANP) found in atria Figure 20-16

Potassium Balance Regulatory mechanisms keep plasma potassium in narrow range Aldosterone plays a critical role (mentioned earlier) Hypokalemia Muscle weakness and failure of respiratory muscles and the heart Hyperkalemia Can lead to cardiac arrhythmias Causes include kidney disease, diarrhea, and diuretics

Disturbances in Volume and Osmolarity Figure 20-17

Volume and Osmolarity

Volume and Osmolarity

Volume and Osmolarity

Volume and Osmolarity Figure 20-18 (1 of 6) Blood volume/ Blood pressure CVCC Parasympathetic output Sympathetic Heart Force Rate Cardiac Vasoconstriction Peripheral resistance Arterioles DEHYDRATION CARDIOVASCULAR MECHANISMS Carotid and aortic baroreceptors Blood pressure Figure 20-18 (1 of 6)

Volume and Osmolarity Figure 20-18 (2 of 6) Blood volume/ Blood pressure Osmolarity accompanied by Distal nephron Vasopressin release from posterior pituitary Volume H2O reabsorption H2O intake Thirst Hypothalamus DEHYDRATION HYPOTHALAMIC MECHANISMS Hypothalamic osmoreceptors Atrial volume receptors; carotid and aortic baroreceptors Blood pressure + Figure 20-18 (2 of 6)

Volume and Osmolarity Figure 20-18 (3 of 6) Blood volume/ DEHYDRATION Blood pressure Granular cells GFR Flow at macula densa Angiotensinogen ANG I ACE ANG II Volume conserved DEHYDRATION RENIN-ANGIOTENSIN SYSTEM RENAL MECHANISMS + Renin Figure 20-18 (3 of 6)

Volume and Osmolarity Figure 20-18 (4 of 6) Blood volume/ Blood pressure Osmolarity Granular cells accompanied by CVCC Angiotensinogen ANG I ACE ANG II Aldosterone Na+ reabsorption Distal nephron Vasopressin release from posterior pituitary Arterioles Thirst Adrenal cortex DEHYDRATION RENIN-ANGIOTENSIN SYSTEM + Renin osmolarity inhibits Figure 20-18 (4 of 6)

Volume and Osmolarity Figure 20-18 (6 of 6) Blood volume/ Blood pressure Osmolarity Granular cells GFR Flow at macula densa accompanied by CVCC Parasympathetic output Sympathetic Heart Force Rate Cardiac Vasoconstriction Peripheral resistance Angiotensinogen ANG I ACE ANG II Aldosterone Na+ reabsorption Distal nephron Vasopressin release from posterior pituitary Arterioles Volume H2O H2O intake Thirst conserved Hypothalamus Adrenal cortex DEHYDRATION CARDIOVASCULAR MECHANISMS RENIN-ANGIOTENSIN SYSTEM RENAL HYPOTHALAMIC Carotid and aortic baroreceptors Hypothalamic osmoreceptors Atrial volume receptors; carotid and aortic Blood pressure + Renin osmolarity inhibits Figure 20-18 (6 of 6)