Contorl Of Potassium Flashcards
Describe the distribution o K+ in body fluids
98% in ICF, only 2% in ECF Mainly in skeletal muscle cells (also liver, red cells, bone)
Shift of 1% of ICF K+ to ECF would raise ECF [K+] by 50%
Difference between ICF & ECF [K+] maintained by Na-K-ATPase Maintaining ECF [K+] is critical
Why is maintaining [K+] critical?
- Because of its effect on the resting membrane potential
- Hence its effects on excitability of cardiac tissue
- Hence risk of life threatening arrhythmias with hyperkalaemia and hypokalaemia
How is ECF K+ regulated
– Immediate Control By internal balance Moves K+ between ECF and ICF – Longer term, overall K+ balance By external balance adjusting renal K+ excretion
What are potassium rich foods
Raisins, honey dew, banana, orange, tomato, potato chips, baked potato, milk
Describe he events following an average meal
• Intestine and colon absorb dietary K+
• E.g. If 28 mmol K+ absorbed
— ECF K+ will increase by 2mmol/L
— If pre-meal K+ was 5 mmol/L could rise to 7 mmol/L (which is a dangerous level)
• But 4/5ths moves into cells within minutes
• After slight delay kidneys begin to excrete K+
Excretion complete in 6 -12 hours
Describe K+ balance following a K+ load eg average meal
See slide
Decsribe the internal balance of K+
Is the net result of
1. Movement of K+ from ECF -> into cells
mediated via Na-K-ATPase
2. Movement of K+ out of cells into ECF
Via K+ channels (channels which determine the K+ permeability of the cell membrane)
What increases K+ uptake by cells
1. Hormones (Act via Na-K-ATPase) • Insulin, • Aldosterone • Catecholamines 2. Increased [K+ ] in ECF 3. Alkalosis - low ECF [H+] K+ shift -> into cells (more later)
What promote K+ shift out of cells
- Exercise
- Cell lysis
- Increase in ECF Osmolality
- Low ECF [K+ ]
- Acidosis - increase ECF [H+]
— K+ shift -> out of cells
(more later)
Describe the effect of K= o insulin
• K+ in splanchnic blood stimulates insulin secretion by pancreas
• Insulin increases Na-K-ATPase activity -> increases K+ uptake by
muscle cells and liver
Clinical Use: I.V. insulin + Dextrose used treat hyperkalaemia
Describ ethe effect of K+ on aldosterone
Aldosterone
– K+ in blood stimulates Aldosterone secretion
– stimulates uptake of K+ via Na-K-ATPase
Desctibe the relation between k+ and catecholamines
Catecholamines
– Acts via B2 adrenoceptors
– Which stimulate Na-K-ATPase and cellular uptake of K+
Describe excerciese and K+
• Net release of K+ during recovery phase of action potential, K+ exits cell (K+ channels open)
• Also skeletal muscle damage during exercise releases K+
• -> increase in plasma [K+] is proportional to the intensity of exercise
• Uptake by non-contracting tissues prevents dangerously high
hyperkalaemia
• Exercise (& trauma) also increase catecholamines, which
offset ECF [K+] rise by increasing K+ uptake by other cells
• Cessation of exercise results in a rapid ↓plasma [K+], often to
<3mmol/L
Describe the acid base disturbances to K+
• Affect several acid-base, Na+ and K+ transport pathways across
cell membrane
• Final result is as if there is a reciprocal shift of H+ and K+
between the cells and ECF
— acidosis shift of H+ into cells, reciprocal shift o K+ out of cells leading to hyperkalaemia
— alkalosis shift of H+ out of cells, reciprocal shift of K+ into cells, leading to hypokalaemia
How can changes in [K+] affect pH
Hypo & Hyperkalaemia Similarly, changes in ECF [K+] causes reciprocal shifts in K+ and H+ between the ECF & ICF
Hyperkalaemia, shift of K+ into cells
Reciprocal H+ shift out of the cells
Hyperkalaemia leads to acidosis
Hypokalaemia shift of K+ out of cells Reciprocal H+ shift into the cells
Hypokalaemia causes alkalosis
Describe the external balance of K+
• Slower • 6 -12 hours to excrete a load of K+
• Controls total body potassium content over the Longer term
• By regulated K+ secretion in late DT & cortical collecting ducts
Around 90-95% Gi absorption, rest is lost
Describe the renal handling of K+
K+ freely filtered at glomerulus
K+ reabsorbed at PCT, Thick AL, DCT, CCD, MCD
K+ also secreted at DCT and CCD (principal cells)
Describe K+ secretion in DCT and CCD
By principal cells Na-K ATPase activity in Basolateral membrane:
High intracellular K+ & low Na+
high intracellular K+ creates chemical gradient for secretion
Na+ moves from lumen into cell down its concentration gradient (via apical ENaC ) creating an electrical gradient - negative potential outside cell
Together create a favourable electro chemical gradient for K+ secretion via apical K+ channels
What are the tubular factors affecting K+ secretion by principal cells
• ECF [K+]
– Directly stimulates Na-K-ATPase &
Increases permeability of apical K+ channels
– Also stimulates aldosterone secretion
• Aldosterone — increases transcription of relevant proteins:- — increase Na-K-ATPase — increase K+ channels & — increase ENaC in apical membrane
• Acid base status - Acidosis decreases K+ secretion: inhibits Na-K-ATPase, decreased K+ channel permeability - Alkalosis ↑ K+ secretion: stimulates Na-K-ATPase, Increase K+ channel permeability
Describe luminal factors affecting K+ secretion by principal cell
• Increased distal tubular flow rate washes away luminal K+, increases K+ loss
• Increased Na delivery to distal tubule
More Na absorbed; classic example eg furosemide, blocks Na reabsorption upstream (in tal) so more is available here
results in more K+ loss
Describe k+ absorption in DCT and CCD
- K+ absorbed by intercalated cells
- Active process
- Mediated by H+ K+ ATPase in apical membrane
What are the effects of changing in ECF K+
— Alter cell membrane resting potential
— Alter neuro muscular excitability
• Problems with cardiac conduction & pacemaker automaticity
• Alter neuronal function
• Alter skeletal muscle function
• Alter smooth muscle function
— Result in arrhythmias, cardiac arrest, muscle paralysis
Dont pick it up until quite late
What are the causes of hyperkalaemia rom external balance
Important to know causes bc hard to pick up
May be due to
– Increased intake (unlikely)
only if renal dysfunction is also present Unless: inappropriate doses of IV K+ (dangerous)
– Decreased renal excretion
• Acute or Chronic kidney injury
• Drugs which block potassium excretion
– ACE inhibitors
– K+ sparing diuretics
• Low aldosterone state (addison’s disease) - addisonian crisis - monitor potassium
What are internal shifts that can cause hyperkalaemia
May also be due to internal shifts 1. Diabetic ketoacidosis no insulin; - insulin promotes k+ into cells & plasma hyper osmolarity & metabolic acidosis) 2. Cell lysis muscle-crush injuries, Tumour lysis 3. Metabolic Acidosis 4. (Exercise)
What are the clinical features of kyperkalaemia
- Heart
altered excitability → arrhythmias, heart block
Hyperkalaemia depolarises cardiac tissue - initial increase in excitability, but as time goes on, more fast Na channels remain in inactive form – heart less excitable - Gastro Intestinal
neuromuscular dysfunction
→ paralytic ileus - Acidosis
What are the ECG changes seen in hyperkalaemia
7 mEq/L - HIgh T wave
8 mEq/L - Prolonged PR interval, depressed ST segment, high T wave
9 mEq/L - Atrial standstill, P wave absent, intraventricular block
10 mEq/L - Ventricular fibrillation
What are emergency treatments for hyperkalaemia
1. Reduce K+ effect on heart - prevent arrhythmias IV calcium gluconate – immediate effect 2. Also Shift K+ into ICF by:– – glucose +insulin IV (action in ≈ 30 mins) – Nebulised Beta agonists (Salbutamol) (catecholamines also push K+ into cell) 3. Remove excess K+ – Dialysis
What are the longer term treatments for hyperkalaemia
- Treat cause
stop medications, treat DKA, etc - Reduce intake
- Measures to remove excess K+
– Dialysis ( in acute or chronic kidney injury)
– Oral K+ binding resins to bind K+ in gut (CKI)
What are the causes of hypokalaemia
May be due to 1. problems of external balance – Excessive loss • GI – diarrhoea/ Bulimia /vomiting • Renal loss of potassium can cause loss of K+ Diuretic drugs, Osmotic diuresis (Diabetes) High aldosterone levels 2. Problems of internal balance – shifts of potassium into ICF E.g. Metabolic Alkalosis
What are the clinical features of hypokalaemia
1. Heart : altered excitability → arrhythmias Hypokalaemia hyperpolarised RMP more fast Na channels available in active form → heart more excitable 2. Gastro Intestinal : neuromuscular dysfunction → paralytic ileus 3. Skeletal Muscle: neuromuscular dysfunction → muscle weakness 4. Renal : unresponsive to ADH →nephrogenic DI Polyuria and polydipsia
What are the ECG changes in hypokalaemia
2.5 - Low T wave, high U wave, low ST segment
3 - Low T wave, Hugh U wave
3.5 - Low T wave
What is the treatment 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
