sodium and potassium balance Flashcards
What allows the homeostatic set point of plasma osmolarity?
Semi-permeable membranes allowing movement of H20
What is the normal plasma osmolarity?
285-295mosmol/L
What is the most prevalent and important solute in ECF?
Sodium, 140mmol/L
Is potassium concentration low or high in ECF?
Low 4mmol/L
What is euvolemia?
State of normal body fluid volume
At euvolemia, what effect is had on Na+ intake and through what nucleus does this occur in?
Inhibition of Na+ intake through the lateral parabrachial nucleus
What neurotransmitters does lateral parabrachial nucleus cells respond to when inhibiting Na+ intake
-Serotonin
-Glutamate
(SING) - Serotonin- inhibit- glutamate
What neurotransmitters does the lateral parabrachial nucleus respond to when increasing appetite for Na+?
-GABA
-Opioids
Other than the central lateral parabrachial nucleus control of Na+ intake, what peripheral level controls Na+ intake?
Taste, more Na+ → aversive (less tasty)
Where is most of the Na+ reabsorbed in the nephron?
PCT, 67%
How much Na+ is reabsorbed in the descending and and ascending limb of the nephron respectively?
-None in descending
-25 % in thick part of ascending
What percent of renal plasma enters the tubular system and therefore how do you calculate GFR from renal plasma flow?
20%
GFR = RPF x 0.2
What senses high tubular sodium?
Macula densa
What are 3 main physiological mechanisms that increase Na+ reabsorption and retention?
-Increased sympathetic activity
-Angiotensin II
-Low tubular Na+
How does an increase in sympathetic activity work to increase NA+ reabsorption and retention?
-Stimulates SMC of afferent arteriole so less is filtered
-Stimulates Sodium uptake from cells of the PCT
-Stimulates juxtaglomerular apparatus to release Renin which forms angiotensin II
How does angiotensin II work to increase Na+ reabsorption and retention?
-Stimulates sodium uptake from cells of PCT
-Stimulates aldosterone synthesis
-Stimulates Na+ reabsorption from the collecting duct
How does low tubular Na+ stimulate its own reabsorption/retention?
-Stimulates the release of Renin which is converted into angiotensin II.
What reduces Na+ reabsorption and retention and how does it do this?
Vasodilators - reduces afferent arteriolar pressure so more is filtered to be excreted
ANP (anti natriuretic peptide)- Decreases uptake of Na+ from PCT, DCT, CT
How does low sodium affect Beta1 sympathetic activity?
Decreased sodium → Decreased volume → Decreased BP → Increased Beta1 sympathetic activity
What does decreased Beta1 sympathetic activity due to high sodium induce?
Atrial natriuretic peptide
Where is aldosterone released from?
Zona glomerulosa in adrenal cortex
What 2 factors can aldosterone release be triggered by?
Angiotensin II
OR
Decrease in blood pressure via baroreceptors
How is aldosterone release triggered by increased sympathetic activity?
Increased sympathetic activity stimulates the cells of the juxtaglomerular apparatus to release renin.
-Renin cleaves angiotensinogen to angiotensin I
-Angiotensin I is converted to angiotensin II by ACE
-Angiotensin II stimulates aldosterone synthase
In the collecting duct and DCT, what does Aldosterone trigger the reabsorption of and what 2 effects will this have?
Increased Na+ reabsorption - 35g Na/day
Increased K+ secretion due to reabsorption of Na+ via basolateral Na+/K+ ATPase co-transporter and then secretion into lumen
If aldoesterone is in excess, what state is induced?
Hypokalaemic alkalosis
How does hypoaldosteronism lead to increased renin, angiotensin II and ADH?
Reabsorption of sodium in distal nephron is reduced → increased urinary loss of sodium → ECF volume falls → increased renin, angiotensin II and ADH
What symptoms does this lead to in hypoaldosteronism?
Low blood pressure
Dizziness
Salt cravings - due to reduction of salt
Palpitations - due to change in membrane potential as a result of decreased salt and so there is more norepinephrine release
What 2 proteins are increased as a result of hyperaldosteronism?
ANP and BNP secondary to the increased ECF volume as there is less urinary loss of sodium
What does BNP stand for what does it do?
Brain natriuretic peptide- Cardiac neurohormone biomarker that is secreted from ventricles when they are under increased pressure and stress.
Liddle’s syndrome is an inherited disease of what?
(MUTATED EPITHELIAL SODIUM CHANNEL, ALWAYS ON- TOO MUCH SODIUM REABSORBED) High blood pressure
What is the cause of Liddle’s syndrome?
Mutation in the aldosterone activated epithelial sodium channel
This means that the channel is always ‘on’
When hypertension is resistant to diuretics, what is then used?
Spironolactone - a potassium sparing MR antagonist
In the heart where are the baroreceptors that respond to low pressure?
Atria, Right Ventricle
In the vascular system where are the baroreceptors that respond to low pressure?
Pulmonary vasculature
In the vascular system where are the baroreceptors that respond to high pressure?
Carotid sinus
Aortic arch
Juxtaglomerular apparatus
In the low pressure side, how is low pressure dealt with?
Low pressure → Reduced baroreceptor firing → Signal through Afferent fibres to brainstem → Sympathetic activity & ADH Release
How does the low pressure side deal with high pressure?
High pressure → Atrial stretch → ANP, BNP released
In what 2 ways is low pressure dealt with in high pressure side?
Low pressure → Reduced baroreceptor firing → Signal through Afferent fibres to brainstem → Sympathetic activity and ADH Release
Low pressure → Reduced baroreceptor firing → JGA cells → Renin released
Where is ANP anti natriuretic peptide made?
Atria
What is ANP released in response to?
Atrial stretch
Atrial Natriuretic Peptide leads to the activation of what protein?
Protein kinase G
What are these cellular responses as a result of protein kinase G activation?
Vasodilatation of renal (and other systemic) blood vessels
Inhibition of Sodium reabsorption in PCT and in the CT
Inhibits release of renin and aldosterone
Reduces blood pressure
What is the response to volume expansion within the nephron?
What is the response to volume contraction within the nephron?
What would be the effect on water reabsorption of increased sodium levels reaching the collecting duct and why?
Increased Na+ in the collecting duct means there is increased osmolarity and so it is more difficult to reabsorb water since water will migrate via osmosis into the collecting duct since there is a higher osmolarity here
Through what 3 mechanisms do ACE inhibitors reduce blood pressure?
Explain the mechanism of osmotic diuretics
Give something that will be filtered but not get reabsorbed
This means that the osmolarity of the nephron will increase
Where do osmotic diuretics have the greatest effect?
In the PCT, (where most water reabsorption occurs)
Where do carbonic anhydrase inhibitors act?
PCT as carbonic anhydrase is most active here
How does carbonic anhydrase help to increase water reabsorption in the PCT
By generating bicarbonate ions, (HCO3-) carbonic anhydrase helps to create an electrochemical gradient that promotes the reabsorption of sodium and other ions from the tubular fluid back into the bloodstream.
Where do loop diuretics work?
Thick, ascending limb of loop of Henle
Where do thiazide diuretics work?
DCT
Where do thiazide diuretics work?
DCT
Where do K+ sparing diuretics work?
In the collecting duct
What effect does carbonic anyhdrase have on Na+ re-absorption?
It increases sodium reabsorption
How do carbonic anhydrase inhibitors work?
-They decrease the action of carbonic anhydrase in the PCT which means less CO2 and H2O gets absorbed into the tubule cell.
-The CO2 and water combine into carbonic acid then dissolve into H+ and Bicarbonate HCO3-
-H+ leaves the tubule into the urine/tubular fluid and a Na+ gets reabsorbed
-Carbonic anhydrase stops all this.
How does carbonic anydrase inhibitor affect urinary pH?
Increases it as there is less H+ in the tubular fluid
How do loop diuretics work?
Triple transporter inhibitors - prevent reabsorption of Na+, Cl-, K+
Reduced Na+ reuptake in Loop of Henle
Increased Na+ in the distal nephron
Reduced water reabsorption
How do Thiazide diuretics work?
Inhibit Na+/Cl- symporter and this reduces Na+ reuptake in the DCT
Increased Na+ in the distal nephron
Reduced water reabsorption
Where is the Na+/Cl- symporter found and what affects it?
In the DCT, thiazide diuretics affect it.
What other effect do thiazide diuretics have?
Increases calcium reabsorption into the blood.
How do thiazide diuretics increase calcium reabsorption into the blood
-The sodium potassium ATPase on the basal lateral membrane is unaffected by by the thiazide diuretics.
-To balance all the Sodium leaving the tubule, more sodium gets brought in into the tubule from the blood through the Na+/Ca+ antiporter on the bl membrane which pump Ca+ into the blood.
How do K+ sparing diuretics work?
Inhibits aldosterone function (spironolactone)
This means there is less reuptake of Na+ in the DCT via the epithelial Na+ channels in the principal cells of the DCT.
The lack of sodium coming in means less K+ leaves as there is less need to balance charges
What is the main intracellular ion?
K+
What affects does low K+ have on the heart?
Heart arrythmias - asystole
What is K+ uptake into tissue from plasma stimulated by?
Insulin mainly
Also aldosterone and adrenaline
How does insulin stimulate K+ uptake after dietary intake?
Indirectly
Where is most of the K+ reabsorbed from in the nephron?
PCT
How much K+ is reabsorbed from the Thick Ascending Loop of Henle and what transporter allows this?
20%
Na+K+2Cl- triple transporter
Where is K+ secreted from into the nephron tubule?
DCT - 10-50%
CCD - 5-30%
What 4 factors stimulate K+ secretion from CCD and DCT?
-Increased aldosterone
-Increased tubular flow rate
-Increased plasma pH
-Increased plasma K+
In K+ depletion, how does the reabsorption of K+ change?
Instead of being secreted, in the DCT and CCD, it is reabsorbed from the tubular fluid
This leads to less K+ being excreted
