Flashcards in Session 6 - Control of Potassium (OK+?) Deck (67):
What % of K+ is in the ICF?
What % K+ is in the ECF?
• 3.5 - 5 mmol/l
What is the difference between ICF & ECF maintained by?
How does K+ establish the resting membrane potential?
• Diffusion out of ICF into ECF
• Gives resting cell membrane potential of -90mv
What does an increase in ECF K+ cause?
• Depolarisation of cell membrane
What do a decrease in ECF K+ cause?
Hyperpolarization of the cell
Give a brief overview of K+ ions
• K+ ions are the most abundant intra-cellular cation
• 98% of total body K+ content is intracellular
• 2% is in the ECF
Body tightly maintains plasma K+ in the range of 3.5 - 5.3 mmo
Why is high K+ inside cells and mitochondria necessary?
Maintaining cell volume
Regulating intracellular pH
Controlling cell-enzyme function
What are the metabolic effects of extremely low extracellular K+?
• Inability of the kidney to form concentrated urine
• A tendency to develop metabolic alkalosis
Large enhancement of renal ammonium excretion
Why is low K+ necessary outside cells?
• To maintain steep K+ ion gradient across cell membranes
• Increase in ECF K+ depolarises cell membrane
• Decrease in ECF K+ hyperpolarises the cell membrane
How is potassium regulated?
• Internal balance, maintaining ECF K+
• External balance, adjusts K+ excretion to intake
What is average K+ intake in diet?
40 - 100 mmol/day
How does body prevent huge increase in ECF K+ after eating?
• K+ moves into cells
• Kidneys begin to excrete K+
What is internal balance the net result of?
• Movement of K+ from ECF -> into cells
• Movement of K+ out of cells into ECF
What factors promote the uptake of K+ into cells?
○ Shift of H+ out of cells
○ Reciprocal K+ shift into cells
• Increased K+ in ECF
How does insulin promote uptake of K+ in ECF?
• K+ in splanchnic blood stimulates insulin secretion by pancreas
Insulin stimulates K+ uptake by muscle cell and liver via an increase in Na+/K+ ATP-ase
How does aldosterone promote excretion of K+ into tubule lumen
• Increases the transcription of Na/K/ATPase in basolateral membrane and ENaC/K+ channels in apical membrane
• Increased channel number gives increases K+ excretion
What factor can stimulate aldosterone secretion?
How do catecholamines increase uptake of K+ in ECF?
• Act via B2 adrenoreceptors which in turn stimulate Na-K+-ATPase
Outline 5 factors promoting K+ shift out of cell
• Low ECF
• Cell lysis
• Increase in ECF osmolality
• Acidosis - Increase ECF
○ Acidosis, shift of H+ into cells, reciprocal K+ shift out of cells
How does exercise promote K+ shift of cells?
• Skeletal muscle contraction -> Net release of K+ during recovery phase of action potential
• Increase in plasma K+ which is proportional to the intensity of exercise
• Uptake of K+ by non contracting tissues as a result of catecholamine release
How do catecholamines offset ECF rise in K+ during exercise?
• By increasing K+ uptake to other cells
How does cell lysis promote K+ shift out of cells
• Cell lysis causes a release of K+ from ICF into the ECF
• Can be causes by skeletal muscle trauma, intravascular haemolysis and cancer chemotherapy
How does plasma tonicity cause K+ movement from ICF to ECF?
• Increase in plasma & ECF tonicity
• Water moves from ICF into ECF
• Increase in K+ in ICF
K+ moves down conc grad out of cell
What does acidosis do to K+ conc in cell?
• Shift of H+ into cells
• Reciprocal K+ shift
• Out of the cells
• Causes hyperkalaemia
What does akalosis do to K+ concentration in cell?
• Shift of H+ out of cells
• Reciprocal K+ shift
• Move into cells causes hypokalaemia
How is potassium balanced?
• External balance
• Internal balance
What is external balance?
• Regulates total body K+ content
• Depends on dietary intake, and excretion
• Responsible for the long-term control of K+
How is external balance controlled?
• Controlled by renal excretion
What is internal balance?
• Regulates K+
• Responsible for moment to moment control
• If ECF/Plasma (K+) increases, K+ moves into cells ○ ECF -> ICF
• If ECF/plasma K+ decreases, K+ moves out of cells
○ ICF -> ECF
○ K+ channels
Give three hormones which cause movement of K+ from ECF to ICF?
What does insulin do to promote movement of K+ from ECF to ICF?
• K+ in splanchnic blood stimulates insulin secretion from the pancreas
• Insulin increases the amount of Na-K-ATPase as it provides the drive for the Na-glucose transporter
• Increases K+ uptake
How do catecholamines promote movement of K+ from ECF to ICF?
• B2 adrenoreceptors stimulate Na/K+/ATPase
• Exercise and trauma increases K+ exit from cells (ICF to ECF), but also increases catecholamines to help offset the ECF (K+) rise
What happens to K+ in kidney?
• K+ reabsorbed
• K+ secreted
Where is K+ reabsorbed in the kidney?
• Proximal tubule
• Thick ascending limb of loop of henle
• Distal tubule/Cortical collecting duct (intercalated cell)
• Medullary collecting duct - intercalated cells
Where is K+ secreted in the kidney?
• Distal tubule and cortical collecting duct
• principle cells
How is K+ reabsorbed in proximal convoluted tubule and in what quantities?
• Passive process
• By paracellular diffusion
○ 67% reabsorbed regardless of diet
How is K+ reabsorbed in thick ascending limb of loop on henle, and it what quantities?
• Active process (Driven by Na-K-ATPase pumps in basolateral membrane)
• Na-K-2Cl transporter in apical membrane
○ 20% reabsorbed regardless of diet
What occurs in the principle cells of the DCT and cortical collecting duct in a high K+ diet?
• Substantial secretion (15-20%)
What occurs in the principle cells of the DCT and cortical collecting duct in a low K+ diet?
• Little secretion
What occurs in the intercalated cells of DCT and cortical collecting duct and medullary collecting duct?
• 10-12% K+ reabsorbed regardless of diet
How is K+ secreted from principal cells in the DCT and cortical CD
• Passive process driven by electro-chemical gradient
• ENAC reabsorption of Na+ drives secretion of K+ through separate channel, creating a negative charge in the lumen
• Process driven by Na+/K+ATPase, which created gradient for Na+ reabsorption
What are the two main factors which affect K+ secretion by principal cells?
• Tubular factors
• Luminal factors
What are three tubular factors affecting K+ secretion
• K+ in ECF
• Acid base status
What are two luminal factors affecting K+ secretion?
• Increase distal tubular flow rate
• Na delivary to distal tubule results in more K+ loss
How does high K+ in ECF effect K+ secretion in principal cell?
• Stimulates NaKATPase and increases permeability of apical K+ secretion
• Stimulates aldosterone secretion
How does aldosterone affect secretion by principal cells?
• Increase transcription of relevant proteins, such as
○ K+ channels & ENAC in apical membrane
Gives increased K+ excretion
How does acid base status affect secretion of K+ ions from principle cells?
• Acidosis decreases K+ secretion - Inhibits Na/K+/ATPase, decreases K+ channel permeability
• Alkalosis Increase K+ secretion - Stimulates KaKATPase, increase K+ channel permeability
How is K+ reabsorbed in the DCT and cortical CD
• Intercalated cells
• Active process
• Mediated by H+-K+-ATPase (2H+ into lumen, K+ out )
What does hypokalaemia do to an ECG and resting membrane potential?
• Hypokalemia hyperpolarises cardiac cells
○ More fast Na+ channels available in active form
Heart more excitable
What does hyperkalaemia do to ECG and resting potential?
• More fast Na+ channels remain in inactive form
• Heart less excitable
• Hyperkalaemia depolarises cardiac cells
More fast Na+ channels
What is hypokalaemia?
• K+ <3.5 nmol/L
What two things can cause hypokalaemia?
• Problems of external balance
○ Excessive loss
• Problems of internal balance
○ Shifts of potassium into ICF
Outline some causes of excessive loss of K+
• GI - diarrhoea/vomiting
○ Diuretic drugs
§ Osmotic diuresis (diabetes)
Outline a problem of internal balance of K+ causing hypokalaemia
• Shift of potassium into ICF
• Metabolic alkalosis
What are the general effects of hypokalaemia on cardiac cells?
• Hyperpolarises - Faster
• Na+ channels available in active form -> heart more excitable
Give four clinical features of hypokalaemia
• Heart -> Altered excitability -> Arrhythmias
• Gastro intestinal -> Neuromuscular dysfunction -> Paralytic ileus
• Skeletal muscle -> Neuromuscular dysfunction -> Muscle weakness -> Conn's syndrome
• Renal -> Dysfunction of collecting duct cells -> Unresponsive to ADH -> Nephrogenic diabetes insipidus
What ECG changes occur in hypokalaemia?
• Increased amplitude and width of the P wave
• Prolongation of the PR interval
• T wave flattening and inversion
• ST depression
• Prominent U waves (best seen in the precordial leads)
Outline treatment for hypokalaemia?
• Treat cause
• K+ replacement - IV/oral
• If due to high aldosterone
○ K+ sparing diuretics that block action of aldosterone on principal cells
○ K+ sparing - Amiloride
○ Aldosterone antagonist - Spironolactone
What is hyperkalaemia caused by?
Ø >5nmol/l K+
Ø External balance problems
Ø Internal balance problems
Outline the external balance problems which can cause hyperkalaemia
Ø Inadequate renal excretion
○ (Increased intake only causes hyperkalaemia in the presence of renal dysfunction)
o Acute kidney injury
o Chronic kidney injury
o Reduced mineralocorticoid effect
○ Drugs which reduce/block aldosterone action
§ K sparing diuretics
§ ACE Inhibitors
• Adrenal insufficiency
Outline internal balance problems which can cause hyperkalaemia
o Shifts of K+ from ICF à ECF
• Acidaemia (Ketoacidosis / Metabolic Acidosis)
• Cell Lysis
Give three clinical features of hyperkalaemia
○ Neuromuscular dysfunction -> Parlytic ileus
Outline the ECG changes you will see with high serum K+
Prolonged P-R Interval
Tall T waves
ST Segment depression
Widened QRS Interval
What is the emergency treatment for hyperkalaemia?
o Reduce K+ effect on heart
• IV Calcium Gluconate
o Shift K+ into ICF via glucose and insulin IV
• Remove excess K+
Give some of the longer term treatments for hyperkalaemia
• Remove excess K+
○ Oral K+ binding resinds to bind K in the gut
• Reduce intake
• Treat cause