Balance Reg Flashcards
Regulation of sodium intake in brain
From lateral parabrachial nucleus
Normal sodium level -> inhibition of sodium intake through serotonin and glutamate
Decreased sodium level -> increased appetite for sodium through GABA and opioids
Sodium reabsorption in nephron
67% PCT 25% thick ascending limb 5% DCT 3% collecting duct <1% excretion
Increased tubular sodium and macula densa
Increased sodium chlorine uptake via triple transporter
Adenosine release from macula densa cells
Detected by extraglomerular mesangial cells
Reduces renin production of juxtaglomerular cells
Promotes afferent smooth muscle cell contraction
Reduces perfusion pressure and so GFR
Percentage of renal plasma entering the tubular system
20%
Renal plasma flow and GFR
Directly proportionally to MAP up to a certain point where it plateaus
Sympathetic activity and control of sodium excretion
Stimulates smooth muscle cell of afferent arteriole
Stimulates sodium uptake by cells of PCT
Stimulates juxtaglomerular apparatus to produce angiotensin 2
Angiotensin 2 and control of sodium excretion
Stimulate cells of PCT to increase uptake of sodium
Stimulate adrenal gland to make aldosterone to stimulate uptake in distal of DCT and collecting duct
Low tubular sodium and control of sodium excretion
Stimulate production of renin and so angiotensin II in juxtaglomerular apparatus
Atrial naturietic peptide and control of sodium excretion
Vasodilator
Decrease sodium reuptake in PCT, DCT, collecting duct
Suppress production of renin from juxtaglomerular apparatus
Aldosterone synthesised from
From adrenal cortex
Aldosterone release in response to
Angiotensin II
Decrease in blood pressure via baroreceptors
Angiotensin II function
Promote synthesis of aldosterone synthase
Aldosterone synthase function
Causes last two steps of aldosterone production from cholesterol
Aldosterone function
Increased sodium reabsorption
Increased potassium secretion
Increased hydrogen ion secretion
How does aldosterone work
Pass through cell membrane as hormones are lipid soluble
Bind to mineralcorticoid receptor which is inside cytoplasm and bound to protein HSP90
Once bound HSP90 is removed receptor will dimerise and translocate into nucleus, bind to DNA, and stimulate production of mRNA for genes that are under its control
Sodium epithelial channels, sodium potassium ATPase, regulatory proteins
Results in more channels and more active channels
Hypoaldosteronism
Reabsorption of sodium in distal nephron is reduced
Increased urinary loss of sodium
ECF volume falls
Increased renin, Ang II, ADH
Symptoms of hypoaldosteronism
Dizziness
Low bp
Salt craving
Palpitations
Hyperaldosteronism
Reabsorption of sodium in distal nephron is increased Reduced urinary loss of sodium ECF volume increase - hypertension Reduced renin, Ang II, ADH Increased ANP and BNP
Symptoms of hyperaldosteronism
High bp
Muscle weakness
Polyuria
Thirst
Baroreceptors of low pressure
Heart - atria and right ventricle
Vascular system - pulmonary vasculature
Baroreceptors of high pressure
Vascular system - carotid sinus, aortic arch, juxtaglomerular apparatus
Detecting change in blood pressure on low pressure side
Low pressure - reduced baroreceptors firing - signal through afferent fibres to brain stem - sympathetic activity and ADH release
High pressure - atrial stretch - ANP, BNP release
Detecting change in blood pressure on high pressure side
Low pressure - reduced baroreceptors firing - signal through afferent fibres to brainstem and JGA cells, (sympathetic activity and ADH release) and (renin released)
ANP steps
Bind to guanylyl cyclase which causes conversion of GTP to cyclic GTP to activate protein kinase G which leads to cellular response (actions)
Volume expansion leads to
Decreased sympathetic activity leading to reduces sodium reuptake in PCT
Also leading to decreased renin production and thus overall decreased aldosterone and increased sodium excretion
Increased ANP and BNP affecting GFR and sodium reabsorption
Volume contractions causes
Increased sympathetic activity leading to increase in sodium reabsorption and increased renin
Increased AVP production in brain promoting water absorption
Sodium excretion and ECF volume
Reducing sodium reabsorption reduces total sodium level, ECF volume and blood pressure
ACE inhibitors
Diuretic
Prevent ACE to change angiotensin I to angiotensin II
ACE inhibitor effects
Vasodilation
Reduced angiotensin II leads to increased vascular volume and decreased blood pressure
- Direct renal effects - reduced sodium reuptake in PCT and increased sodium in distal nephron
- Adrenal effects - reduced aldosterone
- Indirect renal effects - decreased sodium uptake in collecting duct and increased sodium in distal nephron
- all leading to decreased water reabsorption and thus decreased blood pressure
Carbonic anhydrase inhibitor
Work in PCT as enzymes are most active in this region
Leads to sodium reabsorption and increased urinary acidity - inhibitor stops this
Enzyme turns bicarbonate into CO2, which is reconverted to bicarbonate inside cell which produces proton, thus allowing sodium proton exchange
Loop diuretics
Furosemide
Thick ascending limb of loop of Henle
Triple transporter (sodium potassium chloride) inhibitor which reduces sodium reuptake in loop, increase sodium in distal nephron and reduce water reabsorption
Thiazide diuretics
Work in DCT by blocking sodium chloride uptake transporter
Reduced sodium reuptake in DCT
Increased sodium in the distal nephron
Reduced water reabsorption
Increased calcium reabsorption - explanation
Potassium sparing diuretics
Work in collecting duct
Inhibitor of aldosterone function
Bind to mineralcorticoid receptor and block its function like spironolactone
More potassium goes out to lumen
What stimulates tissue uptake of plasma potassium
Insulin
Also aldosterone and adrenaline
How does insulin stimulate potassium uptake
Indirectly by stimulating sodium proton exchange, thus increasing sodium concentration in cell , which is brought down through potassium sodium exchange
Potassium depletion in kidney
67% out in PCT 20% out in ascending limb 3% out in DCT 9% out in CD 1% excreted
Normal and increased potassium in kidney
67% out in PCT 20% out in ascending limb 10-50% in in DCT 5-30% in in CD 15-80% excreted
Potassium secretion stimulated by
Increased plasma potassium
Increased aldosterone
Increased tubular flow rate
Increased plasma pH
Reason for potassium secretion increase from increased plasma potassium
Increased activity of sodium potassium ATPase
More potassium inside cell, thus more potassium going out
Also change in membrane potential which help to stimulate potassium secretion
Reason for tubular flow rate affecting potassium secretion
Cells of distal cell have primary cilia
As there is increased flow, the cilia stimulate PDK1, which increases calcium concentrations in cells, and thus stimulates activity of openness of potassium channels, allowing potassium to be pumped in by sodium potassium ATPase and then out
Hypokalaemia
Most common electrolyte imbalance
May be from inadequate dietary intake (too much processed food), diuretics (increase tubular flow rate), surreptitious vomiting (reduced intake), diarrhoea (reduced intake) and genetics (Gitelman’s syndrome, mutation in sodium chlorine transporter in distal nephron)
Hyperkalaemia
Common electrolyte imbalance present in 1-10% hospitalised patients
In response to potassium sparing diuretics, ACE inhibitors
In elderly, severe diabetes and kidney disease
