Lecture 8 - Regualtion Of Potassium Flashcards
Briefly describe an action potential:
Cell sits at RMP
If stimulus reaches threshold Voltage gated sodium ion channels open allowing Na+ into cell (depolarisation)
Repolarisation where voltage gated sodium ion channels close and voltage gated K+ channels open, hyperpolarisation occurs
Na/K+ATPase reastablilshes the RMP
What happens to resting membrane potential (RMP) with high extracellular potassium?
RMP is decreased (depolarised/more positive) Meaning less of a stimulus is needed to reach threshold
What happens to resting membrane potential (RMP) with low extracellular potassium?
RMP is increased (hyperpolarised)
Meaning less of a stimulus is needed to reach threshold
What happens to an ECG with Hypokalemia?
Prolonged PR
ST depression
U wave
What happens to an ECG with hyperkalemia?
Wide flat P wave
Wide QRS
ST depression
Tall T wave
Look at the last slide, what pathology does 1 show and 2 show?
1 = hypokalaemia
2 = hyperkalemia
What affect does an increase in extracellular K+ levels (hyperkalaemia) have on the level of stimulus needed for an action potential?
It makes the RMP more depolarised making the cell “hyper excitable” this is because its much closer to threshold potential so needs a smaller stimulus to initiate an action potential
What is the total body composition of water in males?
60% fluid
40% solid mass
What is the distribution of total body water in an adult?
2/3 intracellular water
1/3 extracellular water
Of this 1/3 extracellular water:
-25% plasma
-75% interstitial water
Where is the majority of K+ located in the body?
Inside cells
Small amount in plasma
Why in a crush injury (rhabdomyolysis) does a patient present with hyperkalemia?
Crush injury leads to cell death/bursting leading to the intracellular stores of K+ being released into the plasma (hyperkalaemia)
Where is the majority of K+ reabsorbed from the filtrate in the nephron?
Where else is K+ reabsorbed?
Most (67%) in PCT
Ascending limb via NKCC
DCT
Via what mechanism is K+ reabsorbed by in the PCT?
Solvent drag via paracellular transport
What is the mechanism by which K+ is reabsorbed in the ascending limb of LOH?
NKCC
Where is potassium secreted in the nephron?
What transporter does this?
Collecting duct
ROMK
How are pH and K+ levels in the blood related?
If blood is Acidotic K+ levels are high in plasma
If blood is Alkalotic K+ levels in plasma are low
What are the 2 different cells that act to reabsorb K+ in the collecting duct?
Alpha intercalated cells
Beta intercalated cells
In general when in Acidosis why are K+ levels in blood high (hyperkalaemia)?
Cells in body take up H+ from blood to help make blood less acidic, but in order to do this need to exchange the H+ with a K+
So K+ leaves cell into blood making blood hyperkalemic and H+ leaves blood into cell making it less acidic
In general when in Alkalosis why are K+ levels in blood low (hypokalaemia)?
Cells in body put H+ into the blood to help make blood more acidic, but in order to do this need to exchange the H+ with a K+
So K+ enters the cell from the blood making blood hypokalemic and H+ enters into blood from cell making it more acidic
Via what transporter are H+ and K+ exchanged from cells?
H+/K+ATPase
What cell acts in the Acidosis in the collecting duct?
Alpha intercalated cells (A for acidosis)
What is the overall function of the alpha intercalated cell in the collecting duct when its acidotic in the blood?
To secrete more H+ into CD lumen
Reabsorb more K+ and HCO3-
What is the overall function of the beta intercalated cell in the collecting duct when its alkalotic in the blood?
Reabsorb as much H+ as possible
Secrete K+ and HCO3-
So blood becomes more acidic/less alkalotic
Describe the processes taking place in the alpha intercalated cell in acidosis:
Think of the overall goal of the cell (secrete H+ and reabsorb as much HCO3- and K+)
Look at Neil the nephron
H2O + CO2 makes carbonic acid
Carbonic acid broken down into H+ and HCO3- (carbonic anhydrase)
Apical membrane: (in contact with lumen)
H+ pumped into lumen by H+ ATPase and via H+/K+ATPase (so K+ moves into a-intercalated cell)
Basolateral membrane (in contact with interstitium):
K+ leaks into blood
HCO3- transported into blood but is antiported with Cl- (Cl- goes into cell)
Cl- then leaks back into blood across a channel
Describe the processes taking place in the beta intercalated cell in alkalosis:
Think of the overall goal of the cell
Look at Neil the nephron
Overall goal of B-intercalated cell is to reabsorb as much H+ as possible and secrete/excrete as much HCO3- and K+
So water and CO2 made into carbonic acid, broken down into HCO3- and H+ (carbonic anhydrase)
Apical membrane:
K+ leaks out into lumen via K+ channel
HCO3- moved into lumen but is antiported with Cl- (Cl- moved from lumen into cell)
Basolateral membrane:
Cl- leaks into blood across Cl- channel
H+ ATPase pumps protons into blood
H+/K+ ATPase works to pump H+ into blood and K+ into cell
How can Hyperkalaemia present?
Muscle weakness
Cardiac arrhythmias
What 3 things can cause hyperkalaemia?
Lack of excretion
Release from cells
Excess administration
What conditions can cause hyperkalaemia from lack of excretion?
Addisons disease (lack of aldosterone)
Kidney injury (AKI/CKD)
Acidosis
Diuretics (K+ sparing diuretics)
What can cause hyperkalaemia from release from cells?
Crush injures
What are the 3 emergency treatments for hyperkalaemia?
Calcium Gluconate
Insulin
Calcium resonium
How is calcium gluconate used to treat hyperkalaemia in an emergency?
Doesn’t actually treat the Hyperkalaemia
The Ca2+ stabilises the myocardium preventing arrhythmias
How does insulin treat Hyperkalaemia in an emergency?
It drives K+ into cells
K+ follows glucose
So insulin drives the removal of glucose form the blood into cells so indirectly drives cellular absorption of K+
When giving insulin to treat Hyperkalaemia what should you also give?
Glucose
To prevent hypoglycaemia
How does Calcium resonium treat Hyperkalaemia in an emergency?
Increases loss of K+ via the bowels
This is the only way to actually remove K+ from the body without renal replacement therapy
What long term treatments do you do for hyperkalaemia?
Low K+ diet
Stop offending medications (potassium sparring diuretics)
Furosemide to enhance potassium loss in urine (need to worry about dehydration)
What can cause hypokalaemia?
Reduced dietary intake
Increased entry into cells (alkalotic)
Increased GI losses (vomiting + diarrhoea)
Increased urine loss
What are the clinical signs of hypokalaemia?
Muscle weakness, cramps and tetany
Vasoconstriction and cardiac arrhythmias
Impaired ADH action causing thirst, polyuria and dilute urine
Metabolic alkalosis
Why does Hypokalaemia cause metabolic alkalosis?
H+ moved from blood into the cells leading to increased Intracellular H+ conc
How do you treat hypokalaemia?
Treat the cause of it (diuretics, diarrhoea, poor oral intake of K+)
Give potassium replacement:
Oral - Sando-K, bananas and oranges
IV- add KCl to IV bags
Potassium sparing diuretics - Spironolactone, amiloride
What are some potassium sparing diuretics?
Spironolactone
Amiloride
Why cant you infuse a high amount of K+ into the body?
Causes cell death
