Control of sodium and potassium balance Flashcards
(25 cards)
Purpose of water+ sodium regulation
To maintain constant osmolarity
Decreased dietary Na=?
Decreased body osmolarity (but body can’t let this happen)
Decreased ECF volume
Decreased blood volume+ pressure
Decreased water weight
Increase dietary Na=?
Increased body osmolarity (but body can’t let this happen)
Increased ECF volume
Increase blood volume+ pressure
Increase water weight
Where is Na reabsorped in nephron
65% in PCT (used for absorption of everything else)
25% in ascending loop of henle to create hyperosmolar environment
GFR + Na excretion relation
Increased GFR= increase Na reabsorption+ more Na reaches distal part of nephron
Low Na in blood process
High Na in blood process
Draw diagram (slide 13, lecture 6)
1) Low BP= want to decrease Na secretion to increase water potential
2) Increase sympathetic activity= decrease GFR rate+ cause PCT to reabsorb more Na+ stimulates cells in JGA (granular cells that secrete renin)= Increase Ang II production
3) Ang II reduces diameter of blood vessels+ stimulates Na uptake in PCT+ aldosterone secretion which increases Na uptake in CT and DCT.
4) Low tubular Na when reaches JGA= renin production= AngII production= Aldosterone production
High Na:
Atrial naturietic peptide= changes relative diameters of afferent+ efferent arterioles+ reduces activity of cells in PCT, suppresses renin production from JGA+ suppresses Na uptake from CT
Production of renin
Also in endo
Production of renin through activity of Na+/ K+/Cl- channel that senses Na levels
Not a lot of Na= less Na in macula densa cells= low osmolarity compared to environment= water leaves cells= shrink= produced NO and PGE2= stimulates granular (JGA) cells to produce renin
Grnaular cells also stimulated by local hormones+ sympathetic nervous system
Renin-angiotensin system
Draw (slide 16, lecture 6)
Stimulation+ inhibition of the system (slide 18, lecture 6)
Also in endo
Drugs against this?
ACE inhibitors
Effects of AngII
slide 19, lecture 6
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Aldosterone Synthesised + released from? Released in response to? Stimulates? Causes? Aldosterone excess? Works on which cells? How does it work?
Adrenal cortex
Angiotensin II
Decrease in BP (via baroreceptors)
Decrease in osmolarity of ultrafiltrate
Increased Sodium reabsorption (controls 35g Na/day)
Increased Potassium secretion
Increased hydrogen ion secretion
decrease in blood pressure (via baroreceptors) + decreased osmolarity of ultrafiltrate
Hypokalaemic alkalosis
Principal cells
Binds to TYPE 1 INTRACELLULAR receptors: aldosterone enters → binds to cytosolic receptors → HSP
dissociate → receptors form homo-dimer → homodimer translocates to nucleus → modifies transcription.
Production of transcrtiption factors+ regulatory proteins+ transport machinery=
a) Upregulates production of apical sodium transporters.
b) Upregulate production of basolateral Na+/K+ -ATPase.
c) Upregulate regulatory proteins.channels that are there
Ultimately leads to more reabsorption of Na
Hypoaldosteronism
Clinical signs?
Reabsorption of sodium in the distal nephron is reduced
Increased urinary loss of sodium
ECF volume falls= Dizziness, Low BP, Salt craving, Papitations
Increased renin, Ang II and ADH
Hyperaldosteronism
Clinical signs?
Example?
Reabsorption of sodium in the distal nephron is increased Reduced urinary loss of sodium ECF volume increases (hypertension) Reduced renin, Ang II and ADH Increased ANP and BNP
High blood pressure
Muscle weakness
Polyuria
thirst- Thirst because higher osmolarity than should have= want to take more water to reduce osmolarity
More water drunk= need to get rid of it= polyuria
Liddle’s Syndrome- mutation in the aldosterone activated sodium channel.
Channel is always ‘on’= Always reabsorbing too much Na, results in sodium retention, leading to hypertension
Baroreceptors
Where?
Types?
Responses to baroreceptor activity (slide 29, lecture 6)
Heart: atria, RV
Vascular system: Pulmonary vasculature, Carotid sinus, Aortic arch, Juxtaglomerular apparatus
Low ones= Heart ones+ Pulmonary vasculature
High ones= rest of vascular system
ANP Made where? Released when? Actions? Leads to what?
Arial Natriuretic Peptide
Small peptide made in the atria (also make BNP)
Released in response to atrial stretch (i.e. high blood pressure)
Actions:
Vasodilatation of renal (and other systemic) blood vessels
Inhibition of Sodium reabsorption in proximal tubule and in the collecting ducts
Inhibits release of renin and aldosterone
Increases Na excretion though inhibiting all of this
Reduces blood pressure because getting rid of more wate
ECF volume and blood pressure that lead to increase Na+ and H2O excretion
(slide 31, lecture 6)
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ECF volume and blood pressure that lead to decrease Na+ and H2O excretion
(slide 32, lecture 6)
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Diuretics aim?
Types?
To reduce gradient across tubular wall by increasing amount of solute being delivered to tubular system Osmotic Diuretics Carbonic anhydrase inhibitors Loop Diuretics Thiazides K+ sparing diuretics
Osmotic Diuretics
Where does it act? Examples?
Action?
PCT/descending LoH
Glucose and mannitol
DECREASES the osmotic gradient by raising the osmolarity in the CD tube and so less water is reabsorbed.
Carbonic anhydrase inhibitors
Where does it act?
Action?
PCT
Reduces proton export and thus sodium import in the same antiporter.
Less carbonic anhydrase → less protons → indirect inhibition of proton pump (fewer protons being able to be exported) → thus less sodium reabsorption → more reaches DCT →less water reabsorption.
Loop Diuretics
Where does it act? Examples?
Action?
Ascending LoH
E.G furosemide:
Directly blocks the triple transporter in ascending loop of Henle→ less sodium reabsorption → more Na in tubular fluid→ less water reabsorption
But also decreases Na in interstitium
Thiazides
Where does it act?
Action?
DCT
Directly blocks Na+/Cl- co-transporter → less sodium reabsorption → less water reabsorption
Increases plasma Ca2+:
- Under normal conditions when pumping out sodium= low Na conc. In cell
- Na passively enters into cell either through Na/Cl- co transport on apical membrane or 3Na+/ Ca2+ exchange (counter transport) on basolateral membrane
- Thiazide blocks Na/Cl- co transport protein= only way to bring Na in is through countertransport
- Decreased Ca in cell
- More Ca comes in through passive system on apical membrane
K+ sparing diuretics
Where does it act? Examples?
Actions
Side effects?
DCT
E.G. amiloride – blocks Na+ channels
E.G. spironolactone – aldosterone antagonist.
Decrease Na coming in= decrease Na going out= decrease amount of K that enters cells+ decrease K that gets excreted
Aldosterone affects all of these components by increasing expression of channels on both sides of membrane
Spironolactone will inhibit aldosterone= inhibits activity of Na channel+ Na/K ATPase
But they produce small natriuresis
K+ regulation Effect of high+ low extracellular K+ After a meal? Most of K+ reabsorbed where? K+ secretion by? Regulated by? Stimulated by?
High – depolarises membranes → Action potentials and
heart arrhythmias.
Low – heart arrhythmias (asystole)
After a meal, a lot of food is intracellular= lots of K+ into system
Taken up= increase plasma K+= tissue uptake (stimulated by insulin+ regulated by aldosterone+ adrenaline)
All of body involved in taking up K+ so easy to do and K+ doesn’t rise much
Most K+ reabsorbed in PCT
Some in ascending limb
Principal cells of CD: Through Na/K pump into cell then it leaks out through transporters on other side
Also regulated by membrane potential= if outside is more positive it wont go outside
1) Aldosterone Stimulates:
Apical Potassium transporter.
Apical sodium transporter.
Basolateral sodium/potassium ATPase
2) Tubular flow:Cells in collecting tubule have cilia
Increase flow= stimulates PDK1=leads through cascade system= increase intracellular Ca2+= activates K channels to release more K
Hypokalemia
Causes?
20% hospital admissions. Causes include:
Diuretics, vomiting, diarrhoea, genetics (Gitelman’s Syndrome).
