Regulation of Plasma Sodium and ECF Volume Flashcards
what does the hematocrit describe? what is it normally?
volume of red blood cells compared to total blood volume
normally about 45%
changes in fluid volume and composition of extravascular fluid reflects what?
changes in intravascular fluid (they are in equilibrium)
where is extra cellular fluid osmolarity and volume sensed? what types of cells are these?
osmolarity- hypothalamic osmoreceptors
volume- stretch receptors in the atria and vasculature (carotid sinus, aortic arch, renal afferent arterioles)
these cells are neuronal
what 4 “effector agents” (organs) cause the necessary changes to correct for change in ECF volume and osmolarity? which are short and which are long term?
the posterior pituitary (long), autonomic nervous system (short), the heart (short) and the kidney (long)
what is the role fo the autonomic nervous system in maintaining ECF volume and osmolarity?
it increases or decreases peripheral vascular resistance and heart rate to maintain blood pressure at a normal range
what does the renin-angiotensin-aldosterone axis regulate?
peripheral vascular resistance and renal Na excretion
what parameters are used to regulate ECF osmolarity? volume?
osm: renal free water excretion and water consumption
vol: blood pressure and sodium excretion
what determines the ECF volume?
total amount of sodium in the ECF
high sodium= larger ECF volume
how much water is in 1 kg? a 1 kg increase in weight reflects a positive Na balance of what?
1 L of water
140 mEq NaCl
expansion of ECF volume results in what in the kidney? volume contraction?
expansion- increase in output of sodium and water in urine
contraction- decrease in output of sodium and water
the initial absorption of Na after a salty meal has what effect?
induces increased release of ADH into the circulation
increases thirst and absorption of free water in the kidney
(maintains osmolarity and increases plasma volume)
how is the increase in plasma volume from a high salt diet reduced over time?
by gradually decreasing renal sodium resorption and increasing excretion
what is the initial effect in decrease of sodium consumption?
decrease in plasma osmolarity which decreases ADH
decrease in thirst and resorption of free water in the kidney (concentrates and decreases plasma)
how is the volume contraction of a low sodium diet reduced over time?
gradual regulatory increase in renal Na absorption and decreased excretion
an excess of salt in the diet can lead to what phenomenon? why is this important with increasing age?
has clinical effect of raising blood pressure
important because off loading excess sodium is more difficult with age
what is the kidney’s response to ECF volume expansion? volume contraction? what is the change in GFR?
expansion- decreasing Na and water resorption
contraction- increasing sodium and water resorption
no change in GFR unless severe volume contraction
how long does a change in sodium in the diet take to balance with sodium output? what is the detector for this correction?
4-5 days–very closely regulated
detected by baroreceptors that detect the secondary volume change that accompanies the salt intake
compare the osmolarity and volume that is achieved after a increased Na consumption with normal conditions.
there is an isosmotic expansion of ECF volume
what circumstance does the kidney react to to increase Na excretion?
in response to increase in ECF volume, not an increase in sodium concentration
what changes induce regulation of sodium excretion?
changes in effective circulating volume, not total ECF volume
what is the effective circulating volume?
functional blood volume reflecting extent of perfusion where blood pressure is sensed
when does the effective circulating volume not match total ECF?
may be less in disease states that cause edema (like congestive heart failure)
decrease in renal perfusion pressure does what? what does this lead to in the context of edema?
activates the renin- angiotensin- aldosterones system
further increases sodium retention and edema
name four edematous disease states.
conesive heart failure, pulmonary edema, liver disease and nephrotic syndrome
what do liver disease and nephrotic syndrome have in common?
both reduce plasma oncotic pressure by either failing to produce (liver) or allowing excretion of (kidney) albumin
what do diuretic drugs do? how does this impact edema?
decrease plasma volume by forcing the kidney to increase sodium and water excretion in the urine
favors absorption of edematous fluid
which central vascular sensors sense low pressure? which sense high pressure? which are more important?
low- atria and pulmonary vasculature (more important)
high- carotid sinus, aortic arch and juxtaglomerular apparatus in the renal afferent arteriole
how do receptors sense the ECF volume?
by sensing vascular pressure changes that occur with changes in volume
what four systems are activated with decrease in effective circulating volume?
renin-angiotensin-aldosterone system, increased renal sympathetic nerve activity, ADH release by the posterior pituitary and decrease in release of atrial natriuretic peptide
how does angiotensin II affect the kidney? aldosterone?
ang- promotes sodium retention by stimulating Na/H exchange in proximal tubule and decreases renal plasma flow promoting increased Na rebsorption
ald- increased sodium resorption by late distal tubule and collecting duct
what does renal sympathetic nerve activity do during decreased intravascular pressure?
induces renal vasoconstriction and increased Na reabsorption
what is the function of atrial natriuretic peptide?
it induces sodium excretion with high atrial pressures
where is renin synthesized and stored? what is its function?
synthesized and stored in granular cells of the juxtaglomerular apparatus of the kidney
converts angiotensinogen to angiotensin I
where is ACE located and what does it do?
on luminal surface of vascular endothelium, particularly in lungs. it converts angiotensin I to angiotensin II
describe the deactivation of angiotensin II
has a short half life due to rapid degredation by aminopeptidases cleaving it into angiotensin III (less activity)
what is the most important factor controlling angiotensin II levels?
renin release
what are the three renal mechanisms that regulate renin release?
local renal baroreceptors in afferent arterioles
decreased systemic pressure influences sympathetic stimulation of the juxtaglomerular apparatus
cells of the macula densa sense tubular fluid sodium concentration
what are the 5 actions of angiotensin II?
induces aldosterone release from adrenal cortex
hypothalamus- increases thirst and induces ADH release
vasoconstricts renal and systemic vessels
enhances Na/H exchange in proximal tubule
induces hypertrophy of renal tubule cells
what is the purpose of renal vasoconstriction induced by angiotensin II?
constricts efferent more than afferent increasing GFR
increases starling forces favoring resorption of tubular fluid by peritubular capillaries
what is the primary long term regulator of salt balance and ECF volume? where is it produced
aldosterone (a mineralcorticoid)
produced in the adrenal cortex
what two effects does aldosterone have on the kidney?
increases resorption of sodium and therefore water
promotes potassium secretion by the distal nephron
in what cells does aldosterone increase Na absorption and where are they? what distinguishes these cells?
principal cells in the late distal tubule and early collecting duct in the renal cortex
express of intracellular aldosterone receptors
in what three ways does aldosterone increase sodium absorption?
increases basolateral Na/K pumps, increases apical membrane Na channels and increases mitochondrial enzymes to make more ATP
what happens to sodium absorbed in the late distal tubule? how does it change the cortico medullary solute concentration gradient?
since it is in the cortex, it is returned to circulation and does not participate in the gradient
how is cortical Na resorption separated from the counter current multiplication system?
there is separate venous circulation in the cortex and in the vasa recta of the medulla
where is most filtered sodium absorbed in the nephron? where is most of the remaining sodium absorbed?
proximal tubule
thick ascending limb of the loop of henle
how is the loop of henle split functionally? what is the difference?
into the cortical and medullary portions
only medullary portion contributes to the counter current multiplication
how much of Na is reabsorbed in Na balance? what segments account for the variability in that number?
99% of filtered Na is reabsorbed
late distal tubule and early collecting tubule (aldosterone)
what mechanism is not included in the renal handling of Na?
secretion of Na does not occur
describe resorption of NaCl in principal cells of the cortical collecting tubule.
Na is passively absorbed into the cell and actively pumped into the blood via a Na/K pump. Cl follows transcellularly
how is Na absorption coupled to K secretion in the late distal tubule and collecting duct?
increase in Na resorption occurs simultaneously with increase in transcellular K secretion through luminal channels
in what two ways does aldosterone increase K secretion?
by increasing synthesis of the Na/K pump in the basolateral membrane and by increasing synthesis of K channels in the luminal membrane
what is the driving force for paracellular resorption of Cl?
because 3 Na+/2K+ are transported, the transport of Na and K is electrogenic. the negative luminal voltage difference drives Cl movement
how does aldosterone produce effects in the cell?
it binds to an intracellular receptor and induces transcription for membrane transport proteins
what do hormone specific secretogogues refer to?
agents that increase release of hormones into circulation
what secretogogues are there for aldosterone?
angiotensin II (induces ACTH release by anterior pituitary), increased plasma K+ and ACTH
what is the normal plasma sodium concentration?
135-145 mEq/L
what are the symptoms of hypernatremia? at what levels do they become severe?
lethargy, weakness and irritability
>158 mEq/L- seizures and coma may occur
what can cause hypernatremia?
caused by loss of free water from plasma due to inadequate consumption in excess of solute or inappropriate renal excretion of water
what are the possible causes of hypovolemic hypernatremia?
inadequate water consumption, extreme sweating, severe diarrhea and polyuria (like in diabetes mellitus and insipidus)
how does diabetes mellitus cause hypernatremia?
glucose transport is maximized and there is still excess in tubular fluid. this opposes reabsorption in distal nephron segments and prevents water resorption
what is central diabetes insipidus?
inadequate release of ADH from the posterior pituitary to an increase in plasma osmolarity. free water is not reabsorbed and is excreted in the collecting duct
what is nephrogenic diabetes insipidus?
inability of the collecting tubule to respond to ADH despite adequate release
when does hypervolemic hypernatremia occur?
with consumption of hypertonic NaCl solution (seawater) or from inappropriate IV infusionof hypertonic saline
may also occur from hyperaldosteronism
in the case of hyperaldosteronism, how do central osmoreceptors change? how does this effect ADh release?
central osmoreceptors decrease sensitivity and for given increase in plasma osmolarity there is less ADH release
what are the symptoms of hyponatremia? at what level do they get more severe?
nausea, vomiting, headache, lethargy, fatigue, loss of appetite, muscle weakness, spasm and cramps
<125 mEq/L neurological deficis, brain swelling, seizures and coma occur
what are some causes of hyponatremia?
extreme excessive consumption of water and inappropriate increase in free water reabsorbed secondary to dysregulation of ADH (syndrome of inappropriate ADH release)
what is SIADH?
syndrome of inappropriate ADH release when levels are elevated with plasma osmolarity is reduced
is hyponatremia typically the result of water imbalance or salt imbalance?
water
hypervolemic hyponatremia may result from what 5 conditions?
congestive heart failure, kidney failure, liver failure, syndrome of inappropriate anti diuretic hormone and polydypsia
how does congestive heart failure lead to hypervolemic hyponatremia?
inadequate pumping of blood effectively decreases circulating volume, causing the release of ADH
how does hypervolemic hyponatremia result from kidney failure?
Na reabsorption is not sufficient and there is an over compensation for plasma volume depletion by increasing free water reabsorption in excess of solutes
how does liver failure cause hypervolemic hypernatremia?
effective circulating volume is decreased due to edema and ADH is released
what is psychogenic polydipsia?
compulsive water consumption verging on intoxication. imbalance in consumption and excretion dilutes plasma and increases volume
in what settings does hypovolemic hyponatremia occur?
severe vomiting or diarrhea, hemorrhage, prolonged exercise in heat, diuretic drug therapy and in addison’s disease
how does diuretic drug use cause hypovolemic hyponatremia?
diuretics inhibit sodium reabsorption in the kidney but low plasma volumes increase water resorption in excess of solute
what is addison’s disease? how does this lead to hypovolemic hyponatremia
the adrenal gland does not respond to angiotensin II. kidney is unable to increase sodium resorption in response to volume depletion but water may still be retained
why does plasma volume trump plasma osmolarity?
plasma volume will be protected at the expense of osmolarity becuase adequate circulation must be maintained to deliver oxygen and nutrients
