Fluid and Electrolyte Balance

what does the homeostasis of water and electrolytes depend on?

the integration of kidneys, respiratory, and cardiovascular systems

what are some examples of behavioral mechanisms?

thirst and craving for salt

what is the goal of water balance?

mass balance of intake and loss of water

where is water stored in a 70 kg male?

contains ~42 L of water:

• 2/3 inside cells
• 3 L in plasma
• 11 L in interstitial fluid

what is water gained from?

• 2.2 L/day from food and drink
• 0.3 L/day through metabolic production

where is water lost?

• 0.9 L/day from skin and lungs
• 1.5 l/day in urine
• 0.1 L/day in feces

what are the roles of water and Na+?

ECF (cell volume) and osmolarity

what are the roles of K+?

cardiac and muscle function, contractility

what are the roles of Ca2+?

exocytosis, muscle contraction, bone formation

what is the role of H+ and HCO3-?

body pH

what is the integrated response pathway to decreased blood pressure and volume?

→ decreased blood pressure and volume
→ volume receptors in atria and carotid and aortic baroreceptors
→ trigger homeostatic reflexes
→ targets cardiovascular system → increased CO → vasoconstriction → increased blood pressure
→ targets behavior → increased thirst causes water intake → increased ECF and ICF volume → increased blood pressure
→ targets kidneys → slower response → conserve water to minimize further volume loss

what is the integrated response pathway to increased blood pressure and volume?

→ increased blood pressure and volume
→ volume receptors in atria, endocrine cells in atria, and carotid and aortic baroreceptors
→ trigger homeostatic reflexes
→ targets cardiovascular system → decreased CO → vasodilation → decreased blood pressure
→ targets kidneys → slower response → excrete salts and water in urine → decreased ECF and ICF volume → decreased blood pressure

can the kidneys replenish lost water?

no, can only recycle fluid and conserve volume

what can volume loss be replaced by?

volume input from outside the body

what can volume gain be offset by?

volume loss in the urine

what happens when volume falls too low?

GFR stops

what is medullary interstitial osmolarity?

allows urine to be concentrated

how does fluid in the descending limb of the loop of Henle lose water?

by osmosis to the medulla

what are characteristics of the cells in the thick ascending limb of the loop of Henle?

• impermeable to water
• active transport of Na+

what are characteristics of the distal nephron?

• water permeability is variable
• under control of hormones

what is diuresis?

the removal of excess water in urine

what are diuretics?

drugs that promote urine excretion

what does membrane recycling allow for?

vasopressin to control which parts of the cell membrane are permeable to water in the distal tubule collecting duct

what are aquaporins?

water pores that exist in vesicles ready to insert into the apical lumen of the collecting duct

what is the process of concentration of urine in the nephron?

→ isosmotic fluid leaving the proximal tubule becomes progressively more concentrated in the descending limb
→ only water reabsorbed
→ removal of solute in the thick ascending limb creates hypoosmotic fluid
→ ions reabsorbed but no water
→ permeability to water and solutes in the distal tubule and collecting duct is regulated by hormones
→ variable reabsorption of water and solutes in distal tubule and collecting duct
→ final urine osmolarity depends on reabsorption in the collecting duct

what is the relationship between the cortex and plasma?

cortex is isosmotic to plasma

what happens to the [ ] as you go down the renal medulla?

the renal medulla becomes progressively more concentrated

what are the effects of vasopressin (ADH)?

• with maximal vasopressin, the collecting duct is freely permeable to water
• water leaves by osmosis and is carried away by the vasa recta capillaries
• urine is concentrated

what occurs with the absence of vasopressin (ADH)?

• the collecting duct is impermeable to water
• urine is dilute

how is vasopressin transported in the circulation?

dissolved in plasma

what factors effect the release of vasopressin?

• ↑ osmolarity (hypothalamic osmoreceptor)
• ↓ blood pressure/volume (carotid, aortic, atrial receptors)

what cells/tissues does vasopressin target?

the renal collecting duct

where does vasopressin originate from?

• hypothalamic neurons
• release from posterior pituitary

what does vasopressin cause in tissues?

increased renal water reabsorption

what is the action at the cellular-molecular level from vasopressin?

insets AQP water pores in apical membrane

what are the receptors/second messengers of vasopressin?

V2 receptor/cAMP

what is the process of vasopressin regulation in response to decreased blood pressure?

→ decreased blood pressure
→ carotid and aortic baroreceptors
→ sensory neuron to hypothalamus
→ hypothalamic neurons that synthesize vasopressin
→ vasopressin released from posterior pituitary
→ targets collecting duct epithelium
→ insertion of water pores in apical membrane
→ increased water reabsorption to conserve water in the kidneys

what is the process of vasopressin regulation in response to decreased atrial stretch due to low blood volume?

→ decreased atrial stretch due to low blood volume
→ atrial stretch receptor
→ sensory neuron to hypothalamus
→ hypothalamic neurons that synthesize vasopressin
→ vasopressin released from posterior pituitary
→ targets collecting duct epithelium
→ insertion of water pores in apical membrane
→ increased water reabsorption to conserve water in the kidneys

what is the process of vasopressin regulation in response to osmolarity greater than 280 mOsM?

→ osmolarity greater than 280 mOsM
→ hypothalamic osmoreceptors
→ interneurons to hypothalamus
→ hypothalamic neurons that synthesize vasopressin
→ vasopressin released from posterior pituitary
→ targets collecting duct epithelium
→ insertion of water pores in apical membrane
→ increased water reabsorption to conserve water in the kidneys

what is the mechanism of vasopressin action?

→ vasopressin binds to membrane receptor
→ receptor activates cAMP second messenger system
→ cell inserts AQP2 water pores into apical membrane
→ exocytosis of vesicles into collecting duct lumen
→ water is absorbed by osmosis from medullary interstitial fluid into blood in the vasa recta

what is the goal of renal countercurrent exchange?

[ ] of urine

what are characteristics of renal countercurrent exchange?

• consists of closely associated tubules and capillaries of the vasa recta
• close anatomical association of the loop of Henle and the vasa recta
• urine is concentrated in the collecting tubules
• collectively, the many loops of Henle multiple the [ ] gradient in the interstitium

what is the countercurrent multiplier?

transfers solutes by active transport into the medulla

what is the vasa recta?

removes water and prevents dilution of the medulla interstitial fluid

what role does urea play in renal countercurrent exchange?

increases osmolarity of medullary interstitium

what does the ascending limb do in renal countercurrent exchange?

removes ions from the filtrate making it hypoosmotic

what is renal countercurrent exchange done through?

tubule lumen → tissue interstitium → vasa recta

what is the process of renal countercurrent exchange?

→ filtrate entering the descending limb becomes progressively more concentrated as it loses water
→ thin descending limb → loop of Henle → thick ascending limb
→ blood in the vasa recta removes water leaving the loop of Henle
→ the ascending limb pumps of Na+, K+, and Cl- and filtrate becomes hypoosmotic

what is the process of vasopressin release in response to sodium?

→ ingest salt (NaCl)
→ no change in volume, increased osmolarity
→ vasopressin secreted → increased renal water reabsorption → kidneys conserve water OR increased ECF volume
OR
→ thirst
→ increased water intake
→ increased renal water reabsorption → kidneys conserve water
OR
→ osmolarity returns to normal
OR
→ increased ECF volume
→ slow response: kidneys excrete salt and water → osmolarity returns to normal OR volume and blood pressure return to normal
OR
→ increased blood pressure
→ rapid response: cardiovascular reflexes lower blood pressure
→ ECF volume and blood pressure return to normal

what is the role of aldosterone?

controls Na+ reabsorption in the distal tubules and collecting ducts

what does aldosterone work on?

mineralocorticoid receptors to make new ion channels and pumps for Na+ reabsorption and K+ secretion

what is the process of aldosterone release in response to increased K+?

→ increased [K+]
→ adrenal cortex
→ aldosterone
→ targets principal cells (P cells) in the distal tubule/collecting ducts
→ increased Na+ reabsorption and K+ secretion

what is the process of aldosterone release in response to decreased blood pressure?

→ decreased blood pressure
→ RAS pathway
→ adrenal cortex
→ aldosterone
→ targets principal cells (P cells) in the distal tubule/collecting ducts
→ increased Na+ reabsorption and K+ secretion

what inhibits the adrenal cortex?

very high osmolarity

what is the renin-angiotensin system (RAS)?

juxtaglomerular cells secrete renin enzyme if blood pressure drops

what does renin do?

converts angiotensinogen to angiotensin I

what does angiotensin converting enzyme (ACE) do?

converts angiotensin I to angiotensin (ANG) II

what do naturetic peptides do?

balance RAS system by causing natriuresis (urinary Na+ loss) and diuresis (water loss)

what are atrial naturetic peptides (ANP) release in response to?

increased blood volume and atrial stretch

what is the pathway through the hypothalamus for natriuretic peptides?

→ natriuretic peptides
→ hypothalamus
→ less vasopressin
→ increased NaCl and water excretion
→ decreased blood volume
→ decreased blood pressure

what is the pathway through the kidney for natriuretic peptides?

→ natriuretic peptides
→ targets kidney
→ targets tubule → decreases Na+ reabsorption → increased NaCl and water excretion → decreased blood volume → decreased blood pressure
OR
→ afferent arteriole
→ dilates → increased GFR → increased NaCl and water excretion → decreased blood volume → decreased blood pressure
OR
→ decreased renin
→ decreased blood pressure
OR
→ less aldosterone → increased NaCl and water excretion → decreased blood volume → decreased blood pressure

what is the pathway through the adrenal cortex for natriuretic peptides?

→ natriuretic peptides
→ adrenal cortex
→ less aldosterone
→ increased NaCl and water excretion
→ decreased blood volume
→ decreased blood pressure

what is the pathway through the medulla oblongata for natriuretic peptides?

→ natriuretic peptides
→ medulla oblongata
→ decreased sympathetic output
→ decreased blood pressure

what is the process of the renin-angiotensin system?

→ liver constantly produces angiotensinogen in the plasma
→ renin decreases BP
→ ANG I in plasma
→ blood vessel endothelium contains ACE
→ ANG II in plasma
→ targets arterioles or proximal tubules
OR
→ sent cardiovascular control center in medulla oblongata, hypothalamus, or adrenal cortex

what is the process of the RAS through the arterioles?

→ ANG II in plasma
→ arterioles
→ vasoconstriction
→ increased blood pressure

what is the process of the RAS through the CVCC in medulla oblongata?

→ ANG II in plasma
→ CVVC in medulla oblongata
→ increased cardiovascular response
→ increased blood pressure

what is the process of the RAS through the hypothalamus?

→ ANG II in plasma
→ hypothalamus
→ increased vasopressin OR increased thirst
→ increased volume and maintain osmolarity
→ increased blood pressure

what is the process of the RAS through the adrenal cortex?

→ ANG II in plasma
→ adrenal cortex
→ increased aldosterone
→ increased Na+ reabsorption
→ increased volume and maintain osmolarity
→ increased blood pressure

what is the process of the RAS through the proximal tubule?

→ ANG II in plasma
→ proximal tubule
→ increased Na+ reabsorption
→ increased volume and maintain osmolarity
→ increased blood pressure

what causes K+ disturbances?

kidney disease, diarrhea, and diuretics

what is the narrow range for plasma K+?

3.5-5 mEq/L

what is hypokalemia?

• low K+
• muscle weakness and failure of respiratory muscles and the heart
• more K+ leaves cell and resting membrane potential becomes more (-)

what is hyperkalemia?

• high K+
• can lead to cardiac arrhythmias
• lower gradient between ECF and cell K+ [ ] leading to depolarization

what is the response to hyperkalemia?

secrete aldosterone and enhance Na+/K+ ATPase pump of K+ efflux

what do oropharynx receptors do?

respond to cold water by decreasing thirst to be quenched

what does low Na+ stimulate?

salt appetite regulated by the hypothalamus

what is the relationship between osmolarity and volume?

both can change independently

what occurs during dehydration?

• blood volume/pressure decreases and osmolarity increases
• compensation involves CV responses, ANG II, vasopressin, and thirst

what is the response to a decrease in osmolarity and an increase in volume?

drinking large amount of water

what is the response to a decrease in osmolarity and no change in volume?

replacement of sweat loss with plain water

what is the response to a decrease in osmolarity and a decrease in volume?

incomplete compensation for dehydration

what is the response to no change in osmolarity and an increase in volume?

ingestion of isotonic saline

what is the response to no change in osmolarity and volume?

normal volume and osmolarity

what is the response to no change in osmolarity and a decrease in volume?

hemorrhage

what is the response to an increase in osmolarity and an increase in volume?

ingestion of hypertonic saline

what is the response to an increase in osmolarity and no change in volume?

eating salt without drinking water

what is the response to an increase in osmolarity and a decrease in volume?

dehydration (e.g. sweat loss/diarrhea)

what is the process of dehydration through cardiovascular mechanisms?

→ dehydration
→ decreased blood volume/pressure
→ carotid and aortic baroreceptors
→ CVCC
→ decreased parasympathetic output → heart → increased rate/force → increased CO → increased blood pressure
OR
→ increased sympathetic output
→ heart → increased rate/force → increased CO → increased blood pressure
OR
→ arterioles → vasoconstriction → decreased peripheral resistance → increased blood pressure
OR
→ granular cells
OR
→ decreased GFR

what is the process of dehydration through RAS?

→ dehydration
→ decreased blood volume/pressure
→ granular cells
→ renin converts angiotensinogen to ANG I
→ ACE converts ANG I to ANG II
→ adrenal cortex → decreased aldosterone → targets distal nephron → decreased Na+ reabsorption → decreased osmolarity OR increased volume and blood pressure
OR
→ arterioles
OR
→ CVCC
OR
→ thirst
OR
→ increased vasopressin from posterior pituitary

what is the process of dehydration through renal mechanisms?

→ dehydration
→ decreased blood volume/pressure
→decreased GFR
→ volume conserved
OR
→ decreased flow at macula densa
→ granular cells

what is the process of dehydration through hypothalamic mechanisms?

→ dehydration
→ decreased blood volume/pressure
→ atrial volume receptors, carotid and aortic baroreceptors
→ hypothalamus
→ increased vasopressin release from posterior pituitary → targets distal nephron → increased water reabsorption → decreased osmolarity OR increased volume and blood pressure
OR
→ thirst → increased water intake and reabsorption → decreased osmolarity OR increased volume and blood pressure

how is the dehydration pathway accompanied by increased osmolarity?

→ increased osmolarity
→ hypothalamic osmoreceptors
→ hypothalamus
→ inhibits adrenal cortex → inhibits aldosterone

what is the normal pH of plasma?

7.28-7.42

why is [H+] closely regulated?

changes can alter 3D structure of proteins

what are the effects of acidosis?

neurons become less excitable; CNS depression

what are the effects of alkalosis?

hyperexcitable

what are pH disturbances associated with?

K+ disturbances

what is the response to acidosis/alkalosis?

renal and respiratory compensation can move pH closer to normal, but may not correct the problem

how are organic acids obtained?

through diet and intermediates (e.g. lactic acids)

how are acids obtained?

• through diet and intermediates (e.g. lactic acids)
• e.g. ketoacids (acetoacetic acid) through diabetes
• production of CO2: carbonic acid production