LECTURE 13 (Regulation of electrolytes + Blood volume) Flashcards
What is the first line of defence against changes in ECF K+ concentration?
Redistribution of potassium between the intracellular and extracellular fluid compartments
EXPLANATION:
serves as an overflow for excess ECF K+ during hyperkalaemia and a source of K+ during hypokalaemia
What are the factors that influence the distribution of K+ between the intracellular and extracellular compartments?
- Insulin
[stimulates potassium uptake into cells -> Diabetes mellitus patients cannot do this] - Aldosterone
[stimulates potassium intake into cells -> Conn’s syndrome (too much) leads to hypokalaemia + Addison’s disease (too little) leads to hyperkalaemia] - B-adrenergic receptors
[stimulates potassium uptake into cells -> B-adrenergic receptor blockers (to treat hypertension) cause hyperkalaemia] - Metabolic acidosis increases ECF K+ + metabolic alkalosis decreases ECF K+
[increase in H+ reduces activity of sodium-potassium ATPase -> decreases cellular uptake of K+ -> raises ECF K+] - Cell lysis increase ECF K+
- Strenuous exercise increase ECF K+
- Increased ECF osmolarity decreases ECF K+
[water moves out of cells into ECF by osmosis -> increase in K+ conc -> K+ diffuse out into ECF]
What determines Renal potassium excretion?
- The rate of potassium filtration (GFR X plasma potassium concentration)
- The rate of potassium reabsorption by the tubules
- The rate of potassium secretion by the tubules
Where does most of the day-to-day regulation of potassium excretion occur?
In the late distal and cortical collecting tubules
EXPLANATION: this is where potassium can either be reabsorbed or secreted depending on the needs of the body
How is K+ moved from the blood to the tubular lumen?
Through principal cells which are found in the late distal and cortical collecting tubules
MECHANISM:
1) Sodium-potassium pump in the basolateral membrane moves sodium out of the cell into the interstitium + moves potassium into the interior of the cell
[increases K+ concentration in inside of cell so it can diffuse out]
2) Passive diffusion of K+ from inside the cell into the tubular fluid
What controls potassium secretion by principal cells?
- Activity of sodium-potassium ATPase pump
- Electrochemical gradient for K+ secretion from blood to the tubular lumen
- Permeability of luminal membrane for K+
What happens during K+ depletion in the blood?
Reabsorption of K+ from the tubular lumen occurs through INTERCALATED CELLS by a hydrogen-potassium ATPase pump in the luminal membrane [reabsorbs K+ in exchange for for H+ ions into the tubular lumen]
What are the main factors that influence K+ secretion by principal cells?
- Increased ECF K+ concentration
- Increased aldosterone
- Increased tubular flow rate
ADDITIONAL INFO: one factor that decreases K+ secretion is increased H+ concentration (acidosis)
How does increased ECF K+ concentration raise K+ secretion?
- Stimulates sodium-potassium ATPase pump
[increases intracellular K+ concentration causing K+ to diffuse into tubule] - Increased the potassium gradient from the renal interstitial fluid to the interior of the epithelial cell
[reduces back leakage of K+ ions from inside the cells through the basolateral membrane] - Stimulates aldosterone secretion by adrenal cortex
[stimulates K+ secretion]
How does Aldosterone stimulate K+ secretion?
- Stimulates active reabsorption of Na2+ by principal cells of late distal tubules + collecting ducts
[causes K+ to be secreted] - Increases permeability of luminal membrane for K+
How does increased distal tubular flow rate stimulate K+ secretion?
When K+ is secreted into the tubular fluid, luminal concentration of K+ increases, reducing the driving force for K+ diffusion across luminal membrane -> With increased tubular flow rate, secreted K+ is continuously flushed down the tubule -> rise in tubular K+ concentration is minimised
What is the difference between acidosis and alkalosis in K+ secretion?
- Acidosis (increase in H+ in ECF) = reduce K+ secretion
- Alkalosis (decrease in H+ in ECF) = increases K+ secretion
EXPLANATION: increased H+ reduces the activity of the sodium-potassium ATPase but with more prolonged acidosis, H+ inhibits proximal tubular sodium chloride and water reabsorption -> stimulates secretion of K+
- chronic acidosis = loss of potassium
- acute acidosis = decreased potassium secretion
What can hypocalcemia and hypercalcemia cause?
Hypocalcemia = increase in excitability of nerve and muscle cells + hypocalcemic tetany
Hypercalcemia = depresses neuromuscular excitability + can lead to cardiac arrhythmias
What are the different forms calcium exist in the blood?
- Ionised form
[the form that has biological activity at the cell membranes] - Bound to plasma proteins
[In acidosis, less Ca2+ is bound to proteins + in alkalosis, more Ca2+ is bound to proteins -> patients with alkalosis are more susceptible to hypocalcemic tetany] - Non-ionised form with anions
How does PTH regulate plasma calcium concentration?
- Stimulating bone resorption
- Stimulating activation of vitamin D (increases intestinal reabsorption of calcium)
- Directly increasing renal tubular calcium reabsorption
Describe calcium excretion by the kidneys
Calcium is both filtered and reabsorbed in the kidneys but not secreted
Renal calcium excretion = Calcium filtered - Calcium reabsorbed
EXPLANATION: most of the Ca2+ is eliminated by the faeces but an increase in Ca2+ intake increases renal calcium excretion
Where does Calcium reabsorption take place?
- MOST in proximal tubule
[usually by paracellular pathways but 20% by trans cellular pathway: Ca2+ diffuses from tubular lumen into cell due to electrochemical gradient + cell is more -ve -> Ca2+ exits by calcium-ATPase pump and sodium-calcium counter-transporter] - Thick ascending limb of loop of Henle
[by paracellular route by passive diffusion (since interstitial fluid is more -ve) + transcellular route stimulated by PTH] - Distal tubule
[diffusion into cell then active transport by calcium-ATPase pump + sodium-calcium counter transporter mechanism]
ADDITIONAL INFO:
Loop of henle + Distal tubule acted on by PTH, Vitamin D and calcitonin (increases Ca2+ reabsorption)
What factors influence Ca2+ renal excretion?
DECREASED CALCIUM EXCRETION
- increase in PTH
[PTH increases calcium reabsorption]
- decrease in ECF volume
- decrease in BP
- increase in plasma phosphate
- metabolic acidosis
- Vitamin D
INCREASE CALCIUM EXCRETION
- decrease PTH
- increase in ECF
- increase BP
- decrease in plasma phosphate
- metabolic alkalosis
Describe renal phosphate excretion
- When less than a certain amount of phosphate is in the glomerular filtrate, essentially all is reabsorbed
- Proximal tubules absorbs 75-80%, distal tubules absorbs 10%, small amount absorbed in loop of Henle, collecting tubules and ducts
- In proximal tubule, reabsorption usually occurs by trans cellular pathway
[enters cell from lumen by sodium-phosphate co-transporter]
How does PTH regulate phosphate concentration?
- PTH promotes bone resorption (dumps large amounts of phosphate into ECF)
- PTH decreases transport maximum for phosphate by renal tubules -> more tubular phosphate is lost in urine
Describe magnesium excretion and reabsorption
Magnesium reabsorption occurs primarily in the Loop of Henle (65%), Proximal tubule (25%) and a small amount in the distal and collecting tubules
WHAT INCREASES MAGNESIUM EXCRETION
- increased ECF magnesium concentration
- extracellular fluid volume expansion
- increased ECF calcium concentration
What are the two factors that influence sodium and water excretion?
- Glomerular filtration rate
- Tubular reabsorption rate
Sodium excretion = Glomerular filtration - Tubular reabsorption
What is the difference between Pressure diuresis and Pressure natriuresis?
Pressure diuresis = the effect of increased blood pressure to raise urinary volume excretion
Pressure natriuresis = rise in sodium excretion that occurs with elevated pressure
Together are called “Pressure natriuresis”
Describe the mechanism for Pressure natriuresis
1) An increase in fluid intake (accompanied by Na2+ intake) above level of urine output causes temporary accumulation of fluid in body -> increase in blood and ECF volume -> increase in mean circulatory filling pressure
2) Increase in pressure gradient for venous return -> increase in cardiac output -> raises arterial pressure
3) Increase in arterial pressure increases urine output by pressure diuresis -> increased fluid excretion balances intake which prevents further accumulation of fluid
In normal conditions, what do the interstitial spaces act as?
An “overflow” reservoir for excess fluid which causes oedema but protects the cardiovascular system from pulmonary oedema and cardiac failure
What effects does the sympathetic renal activity have on sodium and water excretion?
It decreases it by the following mechanisms:
- Constriction of renal arterioles -> decreases GFR of sympathetic activation
- Increases tubular reabsorption of salt and water
- Stimulation of renin release + increase in aldosterone and angiotensin II formation (which increases tubular reabsorption)
What is the role of Angiotensin II?
When sodium intake is elevated above normal, Renin secretion is decreased causing decreased angiotensin II formation.
When sodium decreases, angiotensin II decreases -> decreases tubular reabsorption of sodium and water -> minimises rise in ECF volume and arterial pressure
How does excessive Angiotensin II not usually cause large increases in ECF volume?
High angiotensin II levels initially cause sodium and water retention by the kidneys + small increase in ECF -> initiates a rise in arterial pressure which increases kidney output of sodium and water
[Balance occurs unless person has heart or kidney failure]
What is the role of Aldosterone?
- Make kidneys retain sodium and water but increase potassium excretion in urine
- Reduction in urinary sodium excretion + maintenance of sodium balance
How does high levels of ADH not cause major increase in body fluid volume or arterial pressure but severe reductions in ECF sodium ion concentration?
Increased water reabsorption by kidneys dilutes extracellular sodium + small increase in blood pressure causes loss of sodium from ECF in the urine through pressure natriuresis
What is the function of Atrial Natriuretic Peptide (ANP)?
- Released by the cardiac atrial muscle fibers
- Stimulus for release is increased stretch of atria due to excess blood volume
MOA:
Once released by cardiac atria, ANP enters the circulation + acts on kidneys to cause small increases in GFR and decreases in sodium reabsorption by collecting ducts -> increased excretion of salt and water -> compensates for excess blood volume
What mechanisms cause increased sodium excretion due to increase in ECF volume?
- Activation of low-pressure receptor reflexes that originate from the stretch receptors of the right atrium and pulmonary blood vessels
- Suppression of angiotensin II formation
- Stimulation of natriuretic systems
- Small increases in arterial pressure
What conditions cause large increases in Blood volume and ECF volume?
- Congestive heart failure
[as heart failure reduces cardiac output, there is a decrease in arterial pressure -> kidneys retain salt and water in an attempt to return arterial pressure to normal -> If too severe, kidneys retain volume until person develops circulatory congestion + pulmonary oedema] - Myocardial failure, heart vulvar disease, congenital abnormalities of heart -> increased blood volume as a circulatory compensation
- Any condition that increases vascular capacity (e.g pregnancy, varicose veins)
[reduces mean circulatory filling pressure -> decreased cardiac output + arterial pressure -> salt and water retention by kidneys to compensate]
What conditions cause large increases in ECF volume but with normal blood volume?
- Nephrotic syndrome (loss of plasma proteins in urine due to increased glomerular capillary permeability + sodium retention in kidneys)
[decreased plasma protein concentration decreases plasma colloid osmotic pressure -> fluid out -> oedema] - Liver cirrhosis (reduction in plasma protein synthesis due to destruction of liver cells)
[fibrous tissue which blocks flow of portal blood through liver raises capillary pressure throughout portal vascular bed (fluid + proteins out leads to ascites) + high pressures in portal circulation can distend veins + increase vascular capacity -> medussa]
