Session 6 - Control of Potassium (OK+?) Flashcards Preview

Semester 3 - Urinary > Session 6 - Control of Potassium (OK+?) > Flashcards

Flashcards in Session 6 - Control of Potassium (OK+?) Deck (67):

What % of K+ is in the ICF?

• 98%
• 120-150mmol


What % K+ is in the ECF?

• 2%
• 3.5 - 5 mmol/l


What is the difference between ICF & ECF maintained by?

Na+/K+ ATPase


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
DNA/Protein synthesis
Cell growth


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?

• Hormones
○ Insulin
○ Aldosterone
○ Catecholamines
• Alkalosis
○ 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?

• Hyperkalaemia


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
• Exercise
• 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
○ Na/K/ATPase
• 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?

• Insulin
• Catecholamines
• Aldosterone


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

• Aldosterone
• 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
○ Na/K/ATPase
○ 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
• Kidney
○ Diuretic drugs
§ Osmotic diuresis (diabetes)

High aldosterone


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

• Heart
• GI
○ Neuromuscular dysfunction -> Parlytic ileus



Outline the ECG changes you will see with high serum K+

8 mmol/L
Prolonged P-R Interval
Tall T waves
ST Segment depression

9 mmol/L
Widened QRS Interval

10 mmol/L
Ventricular fibrillation


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+
○ Dialysis
○ Oral K+ binding resinds to bind K in the gut
• Reduce intake
• Treat cause


Give some of the longer term treatments for hypokalaemia

• Treat cause
• Potassium replacement - IV/oral
• If due to increased mineralocorticoid activity
○ Potassium sparing diuretics which block action of aldosterone on principal cells