Session 6 Flashcards

Question

Describe the physiological roles of having low extracellular [K+]

Answer 1

[\*] The relatively low extracellular [K+] is necessary for maintaining the steep K+ ion gradient across cell membranes that is largely responsible for the membrane potential of excitable and non-excitable cells. The physiological roles of transmembrane [K+} ratio: * Resting Cell Membrane Potential: Reduced [K+]i/[K+]e =\> membrane depolarisation; Increased [K+]i/[K+]e =\> membrane hyperpolarization. Increased ECF [K+] reduces the gradient and depolarizaes the cell (less negative inside). Decreased ECF [K+} increases the gradient and hyperpolarizes the cell (more negative inside) * Neuromuscular activity: low plasma [K+] leads to muscle weakness, muscle paralysis, intestinal distension, peripheral vasodilation, respiratory failure. High plasma [K+} leads to increased muscle excitability initially and later muscle weakness (paralysis) * Cardiac activity: low plasma K+ leads to slowed conduction of pacemaker activity, arrhythmias whilst high plasma K+ leads to conduction disturbances, ventricular arrhythmias and ventricular fibrillation * Vascular resistance: Low plasma K+ leads to vasoconstriction and high plasma K+ leads to vasodilation.

Answer 2

[\*] Potassium is freely filtered at glomerulus [\*] K+ is reabsorbed in the proximal tubule, thick ascending limb of Loop of Henle, intercalated cells of distal tubule/cortical collecting duct and intercalated cells of medullary collecting duct [\*] K+ is secreted by principal cells in the distal tubule and cortical collecting duct

Answer 3

* The Na-K-ATPase activity in the basolateral membrane creates a high intracellular [K+] and a low intracellular [Na+] * The high intracellular [K+] creates a chemical gradient for secretion * Na+ moves from lumen into cell downs its concentration gradient via ENaC on the apical membrane, creating an electrical gradient (Na+ absorb creates lumen negative potential which promotes K+ secretion into lumen) * A favourable electrochemical gradient for K+ secretion is created via apical K+ cells.

Answer 4

1. ECF [K+] * Directly stimulates Na-K-ATPase and increases permeability of apical K+ channels * Hyperkalaemia stimulates aldosterone secretion (including K+ secretion) 2. Aldosterone – steroid hormne * Increases transcription of relevant proteins - Increases Na-K-ATPase (pumps in the basolateral membrane) and increases K+ channels and ENaC in apical membrane * Leads to increased K+ excretion 3. Acid base status * Acidosis decreases K+ secretion: inhibits Na-K-ATPase, decreases K+ channel permeability * Alkalosis increases K+ secretion: stimulates Na-K-ATPase, increases K+ channel pemeability

Answer 5

* Increased distal tubular flow rate washes away luminal K+, increases K+ loss (quickly washing K+ away therefore maintaining electrochemical gradient) * Increased Na delivery to distal tubule means more Na is absorbed =\> resulting increased K+ loss (through secretion)

Answer 6

* Active process * Mediated by H+ K+ ATPase in apical membrane

Answer 7

* Intestine and colon absorb dietary K+ * Substantial amount of K+ can enter the ECF e.g. 28mmol absorbed K+ =\> distributed in 14 L of ECF increases ECF K+ by 2mmol/L (28/14) * 4/5ths of ingested K+ moves into cells within minutes * After slight delay kidneys begin to excrete K+. Excretion complete in 6-12 hours

Answer 8

[\*] External balance adjusts renal K+ excretion to match intake. * Average K+ intake in diet is 100 mmol/day * 5-10% loss via GI tract, rest absorbed * The kidneys adjust K+ excretion to match intake by controlling K+ secretion (renal excretion) * Slower to act – takes 6-12 hours to excrete a load of K+ * Responsible for control of total body potassium content over the longer term [\*] Internal balance maintains ECF [K+] * Effect is immediate – within minutes * Responsible for moment to moment control of ECF K+ - acts as a buffer * Acts by shifting K+ between ECF and ICF. * If ECF (plasma) [K+] increases, K+ moves into cells * If ECF [plasma) [K+] decreases, K+ comes out of cells Internal balance is the net result of 2 processes: * Movement of K+ from ECF into cells (mediated via Na-K-ATPase) * Movement of K+ out of cells into ECF via K+ channels (ROMK channels which determine the K+ permeability of the cell membrane

Answer 9

1. Hormones (act via Na-K-ATPase) Insulin * K+ in splanchnic blood stimulates insulin secretion by pancreas * Insulin stimulates K+ uptake by muscle cells and livers via an increase in Na-K-ATPase as it provides the drive for the Na-Glucose transporter * The increase in Na-K-ATPase results in uptake of K+ * This is why intravenous insulin is used as an emergency treatment to use bring down dangerously high K+ levels (short term, buying time) Aldosterone * K+ in blood stimulates Aldosterone secretion from adrenal glands =\> Stimulates uptake of K+ via Na-K-ATPase * Aldosterone also increases the transcription of ENaC/K+ channels in the apical membrane which leads to increased K+ secretion Catecholamines * Acts via β2 adrenoceptors which in turn stimulate Na-K-ATPase * Stimulate the cell uptake of K+ * Another emergency treatment is nebulised catecholamines 2. Increased [K+] in ECF (=\> increased K+ movement into cell). 3. Alkalosis – low ECF [H+]: H+ moves out of cells to correct Alkalosis. There is a reciprocal K+ shift =\> into cells (to maintain electroneutrality which could eventually lead to hypokalaemia). This is because changes in ECF pH cause reciprocal shifts in K+ and H+ between the ECF and ICF. Hypokalaemia causes Hyperpolarization because it increases gradient)

Answer 10

1. Low ECF [K+] 2. Exercise * Skeletal muscle contraction =\> net release of K+ during recovery phase of action potential (K+ exits cell) * Also skeletal muscle damage during exercise releases K+ * The increase in plasma [K+] is proportional to the intensity of exercise * Uptake of K+ by non-contracting tissues e.g. liver prevents dangerously high hyperkalaemia * Exercise and trauma also increase catecholamines which offset ECF [K+] rise by increasing K+ uptake by other cells * Cessation of exercise results in a rapid decrease in plasma [K+], often to \<3mmol/L (thought to be one of the contributing factors in sudden death in athletes) 3. Cell lysis (when the membrane ruptures, K+ leaks out) * E.g. trauma to skeletal muscle causing muscle cell necrosis (rhabdomyolysis) – can cause hyperkalaemia * Intravascular haemolysis – (breakdown of RBC within vascular tree) e.g. incompatible blood transfusion, G-6-P-D deficient patients treated with certain drugs * Cancer chemotherapy – tumour cell lysis could lead to intravascular haemolysis which could lead to hyperkalaemia 4. Increase in ECF osmolality (plasma hyposmolarity) * Increased plasma tonicity e.g. in diabetic ketoacidosis could lead to an increase in plasma osmolarity and ECF tonicity * Water moves from cells into ECF * This increases [K+] in ICF * K+ leaves down concentration gradient 5. Acidosis – increased ECF [H+] leads to shift of H+ into cells. There is a reciprocal K+ shift =\> out of cells to maintain electroneutrality. This could lead to hyperkalaemia. Changes in ECF pH causes reciprocal shifts in K+ and H+ between the ECF and ICF.

Answer 11

[Changes in ECF [K+] * Alter cell membrane resting potential (normal Em = -90mV) * Alter neuromuscular excitability Problems with cardiac conduction and pacemaker automaticity Alter neuronal function Alter skeletal muscle function Alter smooth muscle function * Result in arrhythmias, cardiac arrest, muscle paralysis (smooth muscle paralysis, skeletal muscle weakness)

Answer 12

[\*] Hyperkalaemia = [K+] \> 5.0mmol/L Hyperkalaemia depolarises cardiac tissue =\> initially heart becomes more excitable =\> more fast Na channels remaining in inactive form – heart less excitable =\> cardiac arrest **Clinical features** * Heart: altered excitability =\> arrhythmias, heart block * Gastrointestinal: neuromuscular dysfunction =\> paralytic ileus (paralysed gut), abdominal distension * Acidosis

Answer 13

* High T waves * Depressed ST segment * Prolonged PR interval (as heart rate slows) * Eventually Atrial standstill (p wave absent) – intraventricular block * Ventricular fibrillation would eventually lead to cardiac arrest

Answer 14

Emergency treatment * Reduce K+ effect on heart (give intravenous calcium gluconate which stabilizes cardiac RMP and reduces initial cardiac excitability – prevents heart slowing down) * Shift K+ into ICF by glucose + insulin IV, nebulised Beta2-agonists (salbutamol) * Remove excess K+ (dialysis) Longer term treatment: * Treat cause * Reduce intake * Measures to remove K+ e.g. via dialysis or oral K+ binding resins to bind K+ in gut

Answer 15

[\*] Hypokalaemia = [K+] \< 3.5mmol/L * Hypokalaemia hyperpolarises cardiac cells =\> more fast Na channels available in active form =\> heart more excitable **Clinical features** * Heart: altered excitability =\> arrhythmias * Gastrointestinal: neuromuscular dysfunction =\> paralytic ileus * Skeletal muscle: neuromuscular dysfunction =\> muscle weakness * Renal: dysfunction of collecting duct cells =\> unresponsive to ADH =\> nephrogenic diabetes insipidus

Answer 16

ECG changes * Low T waves (low and flat) * High U waves (small deflection following the T wave, best seen in leads V2 and V3 – U-wave size is inversely proportional to heart rate: the U wave grows bigger as the heart rate slows down) * Low ST segment Treatment * Treat cause * Potassium replacement – IV/oral * If due to increased mineralocorticoid activity, potassium sparing diuretics which block action of aldosterone on principal cells e.g. spironolactone.

Answer 17

Problems of external balance * Increased intake of K+ only causes hyperkalaemia if there is renal dysfunction unless inappropriate doses given IV * OR inadequate renal excretion Inadequate urinary excretion of K+ could be due to: * Acute kidney injury * Chronic kidney injury * Reduced aldosterone (with normal functioning kidneys) due to adrenal insufficiency, drugs which reduce/block aldosterone action, K-sparing diuretics and ACE inhibitors (reduce amount of aldosterone) Internal shifts * Diabetic ketoacidosis: no insulin (insulin helps to shift K+ into cells), also hyper osmolarity and metabolic acidosis * Other causes of metabolic acidosis * Cell lysis (muscle-crush injuries) * Exercise

Answer 18

Inadequate intake Problems of external balance - Excessive loss: GI (diarrhoea/bulimia/vomiting); Renal loss of potassium (diuretic drugs, osmotic diuresis from uncontrolled diabetes – polyuria, high aldosterone levels) Problems of internal balance - Shifts of potassium into ICF e.g. metabolic alkalosis * Poor perfusion of a kidney due to renal artery stenosis may result in hypokalaemia =\> macula densa cells release renin =\> angiotensin II stimulates aldosterone which promotes K+ loss. * Cushing’s may also cause hypokalaemia – glucocorticoids in high concentrations can bind to mineralocorticoid receptors (enhanced aldosterone action)

Session 6 Flashcards

(42 cards)