1. Regulation of Na +, K + and water Chapter 14 pages 495 - 503

2. Baroreceptors and Na +  Total Na + content in body is kept relatively constant despite wide variation in Na + intake and loss Na+ excreted = Na+ filtered – Na+ reabsorbed  It would be expected that the body has a sensor of Na + concentration to maintain normal Na + levels  Cardiovascular baroreceptors serve as surrogate Na + sensors, water follows the salt Blood pressure → volume of extracellular fluid → amount of extracellular solutes Most extracellular solutes are Na + and associated anions Therefore blood pressure provides good measure of Na +

3. Baroreceptors and Na +  Cardiovascular baroreceptors initiate renal reflexes to retain or eliminate Na +  Low Na + → low plasma volume → low blood pressure → reduced baroreceptor firing rate → renal reflex to retain Na +  High Na + → high plasma volume → high blood pressure → increased baroreceptor firing rate → renal reflex to eliminate Na +  Renal Na + reflexes can change GFR and filtered Na + load  Reflexes also change reabsorption of filtered Na +

4. Control of GFR  Na + excreted = Na + filtered - Na + reabsorbed  GFR is proportional to filtered Na + since Na + is freely filtered  GFR can be lowered by decreasing filtration pressure Constrict afferent arterioles Dilate efferent arterioles Decreases excreted Na + when blood pressure decreases  GFR can be increased by increasing filtration pressure Dilate afferent arterioles Constrict efferent arterioles Increases excreted Na + when blood pressure increases  Sympathetic system mediates renal baroreceptor reflex

5. Direct and neurally mediated reflex pathways by which GFR and Na+ and Water Excretion Decrease When Plasma Volume Decreases

6. Control of Na + reabsorption  Control of Na + reabsorption more important than GFR in control of Na + balance  Aldosterone is steroid hormone secreted by adrenal cortex that increases Na + reabsorption  Increases number of Na + ATPases in distal tubule and cortical collecting duct Still large amount of Na + involved even though most Na + already reabsorbed by the time filtrate reaches distal tubule Aldosterone plays similar role in large intestine and ducts of sweat glands to prevent Na + loss through feces and skin  Low aldosterone during high Na + intake or low Na + losses  High aldosterone during low Na + intake or high Na + losses

7. Aldosterone, renin and angiotensin  Adrenal cortex needs a signal for adjusting levels of aldosterone secretion  Renin is enzyme secreted by juxtaglomerular cells that signals adrenal cortex to secrete aldosterone  Renin initiates cascade of events that lead to aldosterone secretion by adrenal cortex

8. Macula Densa and the Juxtaglomerular Cells

9. Aldosterone, renin and angiotensin  Renin catalyzes angiotensinogen → angiotensin I  Angiotensin converting enzyme (ACE) found on luminal surface of capillary endothelial cells  ACE catalyzes angiotensin I → angiotensin II  Angiotensin II increases aldosterone secretion which stimulates Na+ reabsorption  ACE inhibitors and angiotensin II receptor antagonists are used to treat hypertension since angiotensin II constricts arterioles Prevent Na + reabsorption and increases urine output via decreased aldosterone levels

10. Renin - Angiotensin System

11. Control of renin secretion  Three mechanisms responsible for determining renin levels  Arterial baroreceptors Renal sympathetic nerves are stimulated by decreased baroreceptor activity Increase renin secretion and Na + reabsorption if arterial blood pressure drops  Renal baroreceptors Juxtaglomerular cells located in walls of afferent arteriole in glomerulus Sense blood pressure due to stretch of afferent arteriole Increase renin secretion and Na + reabsorption if renal blood pressure drops  Macula densa Sense Na + concentration of filtrate in ascending limb of distal tubule Low Na + concentration in filtrate causes increased renin secretion May appear counterintuitive since renin leads to further Na + reabsorption Idea is low filtration pressure is origin of low Na + levels

12. Pathways by which decreased plasma V leads to increased Na+ reabsorption

13. Other factors controlling Na + reabsorption  Atrial natriuretic peptide (ANP) secreted by atria of heart Response to increased atrial distension during cardiac cycle Occurs when plasma volume and venous return increase ANP directly inhibits Na + reabsorption in several tubule regions ANP inhibits aldosterone secretion  Pressure natriuresis Increased Na + loss due to elevated renal blood pressure Produced by local mechanism; not due to external hormonal control Possible mechanism is elevated hydrostatic pressure of capillaries Reduces bulk flow between interstitial fluid and renal capillaries

14. Atrial Natriuretic peptide (ANP) increases Na+ excretion

15. Control of water reabsorption  Water permeability of tubules is controlled by vasopressin (antidiuretic hormone ADH)  Baroreceptor reflexes that detect hypotension increase secretion of vasopressin from pituitary  Net result is increased water permeability of collecting ducts  Increases amount of water reabsorbed from filtrate to restore normal blood pressure

16. Baroreceptor pathway by which vasopressin secretion increases when plasma V decreases

17. Control of water reabsorption  Vasopressin also produces widespread arterial constriction to restore normal blood pressure  High vasopression concentration required to initiate arterial constriction reflex  Requires a sizable drop in blood pressure and baroreceptor firing to increase levels of vasopressin  Generally only relevant during pathologic hypotension caused by hemorrhage or heart failure

18. Osmolarity and water reabsorption  Reflexes that respond to changes in blood pressure and extracellular fluid volume generally involve control of Na + reabsorption Water follows Na + to maintain normal osmotic gradients  Other reflexes such as vasopressin release only affect water reabsorption  Water reabsorption does not have a large effect on plasma volume

19. Osmolarity and water reabsorption  Large amounts of Na + are found only within extracellular fluids Na + reflexes only affect extracellular fluid volume  Water is found in both extracellular and intracellular fluid spaces Majority of fluid volume in body is intracellular Reflexes that affect water only do not have major effect on blood pressure and extracellular fluid volume  Reflexes that affect water reabsorption will affect concentration of solutes or osmolarity

20. Osmoreceptor reflexes  Hypothalamus contains osmoreceptor cells to sense osmolarity of CSF  Increased water intake decreases osmolarity of body fluids Hypothalamic osmoreceptors decrease vasopressin secretion Permeability of collecting ducts decrease Increases excretion of water and osmolarity  Decreased water intake or increased water loss increases osmolarity Hypothalamic osmoreceptors increase vasopressin secretion Permeability of collecting ducts increase Decreases excretion of water and osmolarity  Hypothalamus also responsible for blood pressure → vasopressin reflex Receive inputs from various areas of brain Alcohol inhibits vasopressin release via synaptic inputs to hypothalamus

21. Osmoreceptor pathway that decreases vasopressin secretion and increases water excretion when excess water is ingested

22. Sweat, thirst and appetite  Sweat is hypoosmotic fluid that reduces plasma volume and increases plasma osmolarity Aldosterone and vasopressin reflexes are activated during severe sweating  Hypothalamus is responsible for perception of thirst  Thirst is mediated by Hypotension sensed by baroreceptors Increased osmolarity sensed by osmoreceptors Moisture of mouth and throat

23. Pathways by which Na+ and water excretion decrease in response to severe sweating

24. Sweat, thirst and appetite  Hydroreceptors in GI tract limit water ingestion  Stop intake before normal blood pressure and osmolarity restored  Drive to ingest salt increases when plasma volume or osmolarity is low  Most animals and people will ingest salt whenever they can get it  Excess salt intake is normally balanced by excretion in urine  Excess salt intake can contribute to hypertension

25. Inputs controlling thirst

26. Renal K + processes  Extracellular K + must be tightly regulated Abnormal extracellular K + levels can cause abnormal heart rhythms Muscle cramps also can be result of K + imbalance  Most filtered K + is reabsorbed by tubules  K + levels are controlled by secretion following reabsorption  Secretion occurs through K + channels in luminal membrane of collecting duct epithelial cells  Reabsorption occurs through basolateral K + channels in epithelia throughout the tubule  Elevated intracellular K + levels in tubule epithelial are maintained by basolateral Na + /K + ATPases

27. Renal processing of potassium, K

28. Control of K + levels  Two general mechanisms for control of K + levels  First mechanism is direct result of interstitial K + concentration on Na + /K + ATPase activity Elevated K + will increase Na + /K + ATPase activity and result in elevated tubular K +  Second mechanism is elevated aldosterone secretion in response to elevated extracellular K + Aldosterone increases Na + /K + ATPase Increases both Na + reabsorption and K + secretion

29. Pathways by which increased K+ intake increases K+ excretion

30. Summary of the control of aldosterone and its effects Na+ reabsorption and K+ secretion