Regulation of fluid and electrolyte balance Flashcards
What must overall salt and water balance equal?
What regulates ECF osmolality?
Input must equal output
Kidneys regulate ECF osmolality
What control systems regulate the volume and osmolality of the ECF? How do they regulate?
Effective Circulating Volume (~ ECF volume)
Regulated by monitoring arterial volume/pressure and regulating the total body content of Na
Extracellular osmolality
Regulated by monitoring and adjusting total body
water content
both have same actions on the kidneys, but use different mechanisms
How is the ECV determined?
by total body sodium content
How is the sodium concentration and osmolality of the ECF determined?
determined by water balance
What happens if the ECF osmolarity changes?
ECF osmolality and intracellular osmolality must be equal.
if ECF osmolality changes. then the ECF may become hypo or hyper tonic. causing cells to shrink or swell
What is the ECV? What is the ECV connected to?
When is it disconnected?
that part of the ECF volume that is in the arterial system and effectively perfusing tissues
connected to ECF, disconnected in disease states
What is ECV and ECF proportional to? How is long term regulation of fluid balance occurs?
proportional to total body Na+ content*
Na+ loading typically leads to volume expansion
and Na+ loss can lead to volume depletion (where salt goes water goes)
Long term regulation of fluid balance occurs
by regulating the rate of urinary Na+ excretion
Why are patients with HTN are told to watch there salt intake?
Where salt goes, water goes. its an increase in volume. which increases HTN
How does the kidneys respond to a change of ECF?
total body Na content (not concentration) is directly related to ECV
ECF volume increase
-> Kidneys Na excretion increases
ECF volume decreases-> kidneys retains Na
What are the sensors, efferent pathways (long term and short term) Effector(short term and long term and short term), and what is affected(short term and long term)?
ECV(Na content)->
sensed by (Baroreceptors in : carotid sinus, aortic arch, renal afferent arteriole, atria) ->
efferent pathway (RAAS, sympathetic nervous system, ANP, ADH) ->
Effector (Short term: heart, blood vessels Long term: kidney) -> affected: Short term: blood pressure Long term: Na+ excretion
What are the pathways activated that act on the kidney in response to low ECV ?
What are the sensors?
RAAS
Sensor = afferent arteriole -> renin
Sympathetic NS
Posterior pituitary (ADH) Sensors: carotid art., aortic arch
ANP secretion by the heart/atria
Sensor = atrial myocytes
How does the kidney respond in response of decreased ECV?
decrease sodium excretion by
increasing tubular reabsorption or by decreasing renal blood flow, GFR
What stimulates renin secretion?
Low pressure in afferent arteriole
Increased sympathetic tone(hypovolemia)
Low [NaCl] in tubule at macula dense (usually due to decreased GFR)
Where is renin found?
JG cells that line the afferent ateriole
What is going to decrease renin release?
Increase afferent arteriole pressure
Decreased sympathetic tone (hypervolemia)
Increased [NaCl] at macula densa (often due to increased GFR)
What is theRenin-Angiotensin-Aldosterone
System (RAAS)?
Angiotensinogen is a protein that is constitutively secreted from the liver and always circulating in the blood; inactive
Renin cleaves off a decapeptide from angiotensinogen to make angiotensin I (Ang I); little/no physiological activity
Ang I circulates through out the body, acted on by angiotensin converting enzyme, ACE. ACE is found on the lumenal membranes of capillary endothelial cells, particularly in the lung [note – ACE is not “in the lung”]
ACE cleaves off two a.a. to make the octapeptide angiotensin II. This is the primary physiologically active form.
While Ang II can act on multiple sites, one of its main targets is the adrenal cortex, where it stimulates aldosterone secretion.
Where does ANGII act?
Systemically
kidney
Aldosterone release
What are ANGII systemic effects?
Vasoconstriction (including afferent and efferent arterioles)
Potentiate release of NOR from postganglionic
sympathetic neurons
Induce thirst and ADH secretion (renal effects)
What are ANG II effects on the kidney?
Stimulates tubular Na+ reabsorption (PCT and eDT)
Impacts renal blood flow and GFR
How does ANG II act on PCT? (which receptors)
What is the effect?
AngII receptors* are found
on both the apical and
basolateral membranes
of the early PCT
Acts to stimulate Na+ reabsorption via the apical NHE3 and basolateral Na-HCO3 co-transporter and Na/K ATPase
Sodium reabsorption pulls water along with it, so water reabsorption increases proportionally
Which on on the receptors does ANGII act on on the eDCT?
NCC
ENAC
What is the effects on Aldosterone?
Regulates the reabsorption of the last 2-3% of the filtered Na+ load
Na reabsorption promotes
K+ secretion (vice versa) in principle cells of ICT, CCD, OMCD
H+ secretion from intercalated cells
What stimulates aldosterone release?
ANGII
Hyperkalemia
Which transporters does aldosterone stimulate the transcription of in the principal cells?
ENaC ROMK SGK1 (regulatory kinase) Na/K pump TCA cycle enzymes
What are the receptors that Aldosterone binds to?
Minneralcorticoids receptors (MR)
What other hormone does MR bind?
Cortisol has similar effects to aldosterone
Which has a greater binding affinity for MR?
Cortisol
How does aldosterone receptive cells bind aldosterone instead of cortisol?
11b-HSD inactivates cortisol to cortisone
What blocks the effects of 11b-HSD?
Black licorice contains glycyrrhizic acid which blocks the action of 11β-HSD and people who consume too much licorice have symptoms that mimic hyperaldosteronism that may lead to excess Na+ retention, hypervolemia and hypertension and hypokalemia.
What activates the sympathetic NS to act on the kidneys?
are large changes in effective circulating volume or Na+ content, i.e., with hemorrhage or when some one is on a chronic low Na+ diet
What does the sympathetic NS activates on the kidneys?
the JGA
the nephron (PCT)
afferent and efferent arterioles
Which receptors does the SNS act on on the JGA and PCT?
Norepinephrine
JGA-B1
PCT- alpha1
What is the effects of the stimulation of B1 receptors on jGA?
renin secretion and (indirectly) increasing aldosterone-mediated Na+ reabsorption
What is the effects of the stimulation of a1 receptors on pct?
stimulation of apical NHE3 and basolateral Na/K ATPase
activity
What does the excessive volume loss trigger?
ADH secretion from posterior pituitary
What are the effects of ADH secretion from the posterior pituitary?
Excessive volume loss enhances ADH secretion
TALH, ICT and CCT, stimulates Na+ reabsorption
vasoconstriction (through V1 receptors. )
Which transporters does ADH stimulate in the TALH,, ICT, CCT?
NKCC-TALH
ENAC-in principal cells of ICT, CCT
What is the effect of ANP?
Promotes urinary Na+ excretion (natriuresis) by increasing GFR and filtered load of Na
direct actions decreasing tubular Na+ reabs
From where is ANP secreted?
atrial myocytes in response to stretch
Where does ANP act?
on the early early distal tubule and the CCD to inhibit Na+ reabsorption
Which channels does ANP act on in the DCT?
Inhibits NCC in the eDCT
Which channels does ANP act on on the CD?
ENaC in CD
Acts directly (cGMP mediated phosphorylation of ENaC) and indirectly (decrease renin secretion)
What decreases the secretion of ANP? What is the effect?
effective circulating volume, less ANP is secreted, decreasing the stimulation for Na+ excretion (in other words, a decreased effective circulating volume downregulates ANP so more Na+ is retained, reducing Na+ excretion)
What will happen in a reduction of ANP?
allow more ADH (vasopressin) to be secreted,
lead to a decrease in GFR and
an increase in renin secretion, and
would remove the inhibitory effects of ANP on tubular Na
reabsorption directly and indirectly by allowing
aldosterone secretion (ie, allow an increase in
aldosterone secretion).
What are the summary effects of decreasing ECV?
decrease stretch on renal afferent arteriole
increase renin secretion-> increase ang II -> increase-> increase aldo -> increase Na+ R
PT (NHE3) CCD (ENaC)
Decrease stretch on carotid artery/aorta ->
increase sympathetic NS (nor) -> increase renin, increase-> Na+ R
ADH secretion Na+/water R in TALH/CD
decresae stretch on atria myocytes
decrease ANP* secretion-> increase Na+ R in DCT,
CCD, IMCD ( decrease Na+ excretion)
What is the sequence that is effected when ECF osmolatity (total body water) is changed?
sensors- hypothalmic osmoreceptors
Efferent pathways - ADH/ thirst
Effector- short term kidney/long term brain:drinking behavior
What is affected- short term urine flow rate/long term water intake
What senses change in ECF osmolality?
hypothalmic osmoreceptors
What is ADH secretion based on when regulating osmolality?
Under normal conditions, little/no ADH is secreted if ECF
osmolality < 280 mOsm (red line)
But the actual threshold and sensitivity is variable and based on effective circulating volume
Above the threshold, ADH secretion is sensitive to even small changes in osmolality
What is the primary stimulus for ADH secretion?
ECF osmolality (1) is primary stimulus for AVP secretion
what is a change in ECF osmolality detected by?
OVLT and SFO in the hypothalmus
What are the stimulus for increase of ECF osmolality?
1) OVLT and SFO in hypothalmus
2) decrease in circulating volume
3) decrease in arterilapressre at the carotid sinus
4angiotensin II also binds to receptors near the hypothalamus to stimulate ADH/AVP secretion
What does ADH stimulate and where?
ADH/AVP binds to V2 receptor on basolateral membrane
V2 = GPCR
cAMP PKA
Phosphorylation cascade leads to insertion of AQP2 containing vesicles to apical membr
