Distribution of body potassium mEq

(intake, excretion, ECF, plasma, ICF and tissues)

• Intake 100mEq
• Stool 10mEq and kidney excretion 90mEq
• ECF 7mEq and plasma 17mEq
• ICF total 3500mEq divided into muscle 2700mEq, liver 250mEq, bone 300mEq and erythrocytes 250mEq

• [potassium]_plasma at rest is around 4mM
• [potassium]_plasma during intense exercise can reach 8mM

Causes and consequences of hyper- and hypokalaemia

• Hyperkalaemia - caused by metabolic acidosis (production of mineral acids from hydrogen ion-potassium ion exchange across cell membrane), renal failure, hypoaldosteronism, tissue breakdown, exercise. Consequences - weakness, fatigue and changes in ECG (tenting of T wave, lengthening and dissapearance of P wave and widening of QRS. High extracellular levels of potassium increase the potassium equilibration potential, resulting in the inactivation of sodium channels and the constitutive depolarisation of myocytes and myocardiocytes. This may result in VF, bradycardia and asystole.
• Hypokalemia - Can be caused by diarrhea, muscle crush injuries, diuretics, Conn's or Cushing syndromes, alkalosis. manifests as weakness, cramps, palpitations, delerium. Low potassium hyperpolarises cells as E_m moves closer to E_k. Action potential duration is elongated as less potassium to rectify polarisation, increasing calcium entry and inotropy. Saturation of SERCA and NCX causes net sodium influx resulting early afterdepolarisations and inefficient heart contraction - drop in stroke volume and blood pressure. ECG - depression of T wave and U wave presentation from EAD 

• Hyperkalaemia can cause acidosis - inhibition of the production of NH₃ through increased serum potassium prevents acid buffering
• Acidosis reduces the secretion of potassium in the collecting duct as increased proton concentration inhibits the basolateral potassium/sodium ATPase and reduces potassium within the cell that is available for expression as well as altering the apical membrane permeability to potassium

Non-renal distribution of potassium

(insulin, catecholamines, exogenous β₂ agonists, aldosterone)

• Insulin decreases plasma potassium by acting on tyrosine kinase receptors to increase the activity of the Na/K ATPase and thus pump potassium into the cell. As well as this, insulin promotes glucose uptake at SGLTs and thus increases intracelluilar sodium and indirectly the activity of the Na/K ATPase
• Adrenaline causes transient hyperkalaemia followed by hypokalaemia. This is due to the instant effects of α (and thus agonists) adrenoreceptors on potassium release on the liver followed by β₂ (and thus agonists) Gs coupled reuptake of potassium in the muscle via cAMP/PKA activation of Na/K ATPase
• Aldosterone causes hypokalaemia through increased excretion at kidneys and nuclear receptor mediated induction of K/Na ATPase

Distribution and total body content of calcium

(mmol/day and moles respectively)

• Distribution in - diet 25mmol/day, 20-22mmol/day lost in faeces. Secretion into gut 15mmol/day, absorption 18-20mmol/day, therefore net absorption is 3-5 daily. ECF & Plasma 20mmol/L, bone 25 000mmol/L (1% exchangable),  net loss 3-5mmol/day through urine.
• Total body calcium is aroud 25 moles, or 1g

• Hypocalcaemia - can be caused by eating disorders, hypoparathyroidism (low PTH), or prolonged vomiting. Consequences through increase in neuronal membrane by increasing sodium permeability and thus causing tetany. QT is also increased and heart failure can occur
• Hypercalcaemia can be caused by hyperparathyroidism as well as vitamin D disorders and high bone turnover. Consequences - urinary stones, polyuria and dehydration

Hormonal regulation of calcium 

(PTH, Vit D, calcitonin)

• PTH - peptide secreted from parathyroid in response to falling plasma calcium sensed by G proteins. Inhibits Na-phosphate contransporter and therefore phosphate reabsorption in the kidney, which in turn increases calcium mobilisation. Increases calcium reabsorption in DCT and CD and increases activity of 1 α-hydroxylase to production 1,25-OHD_3. 
• Vit D - synthesised in skin from cholesterol by UV light. In liver 25-hydroxylase creates 25-OHD₃. In kidney, conversion to active form 1,25-OHD₃ which increases uptake of calcium through synthesis of calbindin in intestine, facilitates conservation of calcium in kidney and inhibits the synthesis of collagen by osteoblasts and acts on osteoclasts to increase bone breakdown
• Calcitonin - produced by C cells of thyroid and secreted in response to increased calcium levels in serium. Via surface cAMP receptors - causes bone uptake and inhibits gut absorption

• Intake = 1/2mg daily
• Iron in plasma not bound to transferritin - 3mg
• In reticuloendothelial system - bone (300mg, RBCs 1800mg, reticuloendothelial macrophages 600mg and 20-25mg/day of movement), 
• Liver 1000mg and 400mg in other cells and tissues
• 1-2mg/day of loss 

Important molecules in iron transport and storage

(name and function)

• DCYT3/DMT-1 - DCYT3 converts Fe³⁺ to Fe²⁺, which is pumped into duodenal enterocytes by DMT-1
• Ferroportin - on basolateral membrane pumps Fe²⁺ out of macrophages (digestion of RBCs) and enterocytes
• GPI-linked ceruloplasmin/hephaestin - conversion of Fe²⁺ back to Fe³⁺ in macrophages and enterocytes respectively
• Transferrin - binds iron for transport in blood. On erythroid cells, binds TfR1 to form internalised complex for STEAP3 mediated conversion to Fe²⁺
• Ferritin - made from 24 subunits - cellular storage of iron and good indicator of body stores 
• Hepcidin - released in liver in response to increased iron and opposes intestinal uptake and release from reticuloendothelial macrophages through the inhibition of ferroportin
• IRPs (iron regulatory proteins) bind DNA and control expression of ferritin (inhibited) and transferrin (activated) during low iron levels - high iron levels cause IRP degradation, and therefore opposite response (increased storage and reduced uptake)

• Erythropoiesis - suppression of ferritin production independent of iron levels
• Hypoxia - reduces hepcidin levels (partly through EPO), as well as through the HIF pathway 
• Inflammation - IL-6 stimulate hepcidin production in attempt to deprive microbes of iron (can lead to anaemia of chronic diseases)

• Acid secretion -  mainly in PT type A intercalated cells - CO₂ and H₂O diffuse into tubular epithelial cells, and is catalysed by carbonic anhydrase to form carbonic acid. Carbonic acid dissociates into H⁺ and HCO_3^-, H⁺ pumped out of apical membrane by H⁺-ATPase and NHE, HCO_3^- pumped across basolateral membrane by anion exchanger (chloride) and with sodium:bicarbonate (3) cotransporter
• Regeneration of bicarbonate - mainly in PT - same process, but excreted H⁺ in lumen combines with bicarbonate to form CO₂ and H₂O. The gases can then diffuse back into the cell, react with CA to form hydrogen ion (recycled once more), and bicarbonate to be recovered across basolateral membrane