Regulation of K+ and Ca2+ Flashcards
Potassium balance
Input = diet, output = excretion, small amount by stool and sweat
Quantities of potassium
3000mmol in the body.
Mostly present in skeletal muscle, some in bone, liver and red blood cells
Plasma concentration = 3.5-5mmol.
Reasons for hyperkalaemia
Renal failure (including due to ACE inhibitors or spironolactone)
Crush injuries
Escape of intracellular K+ following acidosis
Haemolysis - eg in freshwater drowning.
Reasons for hypokalaemia
Excessive diuretics (particularly thiazide)
Severe GI disease
Severe burns
First sign of hyperkalaemia
On the ECG, shortened ST interval and T wave attenuating, as cardiac cells are most sensitive to changing K+. As action potential shortened due to activation of inward rectifier channels, so less time for Ca2+ entry and less CICR = impaired contraction.
Low K+ effect on the heart
De-activation of delayed rectifier K+ channels and other repolarising currents, so increased time for Ca influx (during plateau period), then stimulating the Ca/3Na pump, and have net positive charge into the cell. This is occasionally seen in middle aged men who drop dead due to high sympathetic and low K+ as moer Ca is driven into cells.
List of physiological factors which will alter K+ homeostasis
Insulin Catecholamines Acid-base status Hypoxia Exercise
Exercise changes to K+ homeostasis
Plasma K+ can rise to 9mmol/L, but drops immediately following conclusion of exercise. As muscle cells depolarise then there is a leak of K+ as the Na/K pump cannot keep up, so there is a net efflux into the plasma. On finishing exercise then sympathetic stimulation means that K+ is taken back up effectively.
May be the K+ which causes muscle pain in fatigue, as lactic acid production peaks two minutes AFTER finishing exercise, potentially increased K+ causes depolarisation of sensory nerve endings. Hyperventilation also drives hyperkalaemia?
Skeletal muscle fatigue
High K+ outside leads to depolarisation of cells, such that VG Na channels open but also are more frequency inactivated. This means that action potentials are much more sluggish, and high Na+ is negatively inotropic in muscle.
Myocardial stability in exercise
During exercise there is mutual antagonism between high levels of K+ and high levels of catecholamines, and on balance means increased inotropy and chronotropy, by increasing the action potential current of iCa-L. Exercise induces independent Ca pathways, particularly through angiotensin II?
Signs and symptoms of hyperkalaemia
Glucose intolerance Arrhythmias Orthostatic hypotension Vasodilation Constipation Muscle weakness/paralysus Oedema Reduced aldosterone Reduced GFR
Treatment of hyperkalaemia
Correction of cause.
In an emergency can give intravenous Ca2+ gluconate to maintain inotropic support to the heart, and give insulin and glucose which causes widespread reuptake.
Potential consequences of hypokalaemia
After depolarisation, as cardiac cell cannot deal with extra load of intracellular Ca2+, and attempt to compensate with Ca/3Na pump leads to net influx. Many extra depolarisations may cause the heart to contract prematurely before ventricular filling is complete. Reduced CO = collapse in arterial blood pressure and potential hypoxia.
Hypocalcaemia
Causes nerve hyperexcitability and muscle tetany due to decrease in threshold potential. Reduces myocardial contractility
Hypercalcaemia
Decreased excitability of nerves, causing long-term lethargy. Can often by chronic and generally less dangerous. In extreme situations arrests the heart in systole.
Plasma calcium concentration
Available = 1.2mM
Total plasma = 2.4mM, as 40% is reversibly bound to protein and 10% to citrate and phosphate
Total calcium stores
Total contained = 1kg. Of which 99% is stored in the skeleton, 1% is in the ECF and 0.1% is in intracellular fluid.
Causes of hypocalcaemia
Often secondary hyperparathyroidism due to chronic kidney disease.
Causes of hypercalcaemia
Often urinary stones. Or multiple endocrine neoplasia? Or nephrotic syndrome, where loss of protein through leaky capillaries causes a fall in plasma colloidal osmotic pressure, and normal Ca carrying capacity of protein in plasma reduced.
Effects of pH on plasma Ca
Alkalosis: increases negative charge on plasma proteins, so more Ca binds, potential hypocalcaemia.
Acidosis: opposite
Skeleton Ca flux
Bone is major store of body Ca as hydroxyapatite, but this is continuously dynamically remodelled by osteoblasts, osteocytes and osteoclasts. Mechanical stress stimulates bone formation (hence why disuse causes loss of bone). Non-crustalline Ca salts and fluid are also present in bone and can be immediately accessed in hypocalcaemia.
Vitamin D influence on Ca
The sun drives formation of cholecalciferol in the skin, which is then activated to 1,25-hydroxycholecalciferol in the kidney. This acts as a nuclear receptor to activate transcription, particularly for transporters in the gut, so increasing absorption of Ca and it’s transepithelial transport (TRPV6 and PMCA)
Vitamin D deficiency
Causes rickets in children, where bones are bent due to lack of Ca. In adults causes osteomalacia.
Parathyroid hormone
Mobilises calcium.
REceptors = PTH1 and 2 Rs, present on osteoblast, stimulate osteoblast proliferation in normal growth, when present in pulses. Also increases Ca reabsorption in the distal tubule of the kidney.
Hyperparathyroidism
Increased PTH leads to over activation of the RANK receptor, and so excess stimulation of osteoclasts,
Secondary hyperparathyroidism
Relatively common when have kidney damage so cannot produce vitamin D and Ca in plasma is reduced, so PTH increases and destroys skeleton to compensate.
Calcitonin
Decreases plasma Ca levels. Produced in thyroid and inhibits osteoclast breakdown of bone. Also involved in gut control of Ca by inhibiting absorption.
Lactation calcium balance
PTH stimulates mother’s calcium to be mobilised for the baby. Calcitonin protects against excess loss
Detecting levels of Ca2+
Cells in the parathyroid gland, kidney distal tubule, gut enterocytes and osteoblasts all have GPCR activated by plasma Ca2+ acting via a Gq coupled mechanism.
