Potassium homeostasis

Potassium homeostasis TOTAL BODY K+ = 40-50 mEq/kg - intracellular – 98% - extracellular – 2% PLASMA K+ = 3.5 – 5.0 mEq/l K+ 2K+ ATP K+ 3Na+

RENAL REGULATION OF POTASSIUM HOMEOSTASIS RESPONSE TO K+ DEFICIT adaptation of kidneys during 2-3 days minimal renal K+ excretion = 5 – 15 mEq/day FEK+changes from 17% to 3-5% minimal K+ intake of 10-25 mEq/day is necessary to maintain balance RESPONSE TO K+ EXCESS Renal K+ excretion increases up to tenfold renal reaction starts within hours increased K+ secretion into the colon can support renal action

RENAL POTASSIUM EXCRETION FILTRATION : 700 – 1000 mEq/day EXCRETION: 25 – 100 mEq/day Proximal tubules : reabsorption 40-50% Descending limb of Henle loop: passive diffusion from the interstitium to lumen Thick ascending limb of Henle loop: reabsorption 35-45% Cortical collecting tubules: - reabsortpion in α-intercalated cells, in exchange for H+ secretion - secretion from principal cells Medullary collecting tubules: - reabsorption in α-intercalated cells

K POTASSIUM CHANNELS PRINCIPAL CELL TUBULE K 0 mV Na - 90 mV Na-K-ATPase Na - 90 mV K POTASSIUM CHANNELS CHEMICAL GRADIENT ELECTRICAL GRADIENT

RENAL POTASSIUM SECRETION FROM PRINCIPAL CELLS Luminal K+ conc. = inversely proportional Luminal Na+ conc. = proportional 3. Na+ and K+ conductance in the luminal membrane = proportional 4. Aldosterone = proportional 5. Nonreabsorbable anions in urine = proportional 6. Luminal flow rate = proportional 7. Intracellular K+ conc. = proportional

HYPOKALEMIA Plasma K < 3.5 mEq/L Inadequate potassium intake (less than 20-30 mEq/day) Excessive nonrenal potassium excretion - sweat 1-2 mEq/day => 100 mEq/day - GI tract 10 mEq/day => 100 – 200 mEq/day 3. Renal potassium losses - increased Na+ delivery to cortical tubule - nonrebsorbable anions - primary hyperaldosteronism 4. Potassium translocation into cells (Total K+ unchanged) - hyperinsulinism, hyperaldosteronism, β-adrenergics - rapid proliferation of cells

Membrane potential in hypokalemia Hypokalemia - Muscles - Hyperpolarisation of cells interior => increased threshold for depolarisation K< 2.5 mEq/L => decreased muscles strength Effect stronger in acute hypokalemia; with time its intensity decreases Chronic hyperpolarisation=>Na+ channels are opened=>spontaneous depolarisation Threshold potential -60mV Membrane potential -90mV Membrane potential in hypokalemia

HYPOKALEMIA - SYMPTOMS 1. Heart - heart block and arrhytmias 2. Blood vessels - lack of vasodilation => rhabdomyolysis 3. Endocrine - decreased insulin synthesis

HYPOKALEMIA - SYMPTOMS Kidneys - decreased blood flow => renin synthesis - impaired renal water conservation: - inhibition of ADH renal effect - metabolic alkalosis - intracellular acidosis and extracellular alkalosis - increased ammoniagenesis - increased distal secretion of hydrogen

POTASSIUM DEFICIT REFLECTED BY PLASMA [K+]

HYPERKALEMIA Plasma K > 5.0 mEq/L Excessive potassium load Decreased renal potassium excretion - renal failure - decreased distal delivery of Na+ - hypoaldosteronism Potassium redistribution ICF=>ECF (Total K+ unchanged) - deficient insulin, aldosterone, β-adrenergics) - acidosis - hyperosmolality - cell necrosis

Hyperkalemia - Muscles - Hypopolarisation of the cell membrane => decreased threshold for depolarisation Chronic hypopolarisation => Na+ channels are closed=> reduced depolarisation Threshold potential -60mV Membrane potential in hyperkalemia Membrane potential -90mV

HYPERKALEMIA - SYMPTOMS Muscles - hypopolarisation =>decreased thereshold for depolarisation - chronic hypopolarisation => closing of Na+ channels 2. Heart - accelerated repolarisation and delayd depolarisation - heart block - arrhytmias 3. Blood vessels - vasodilatation 4. Kidney - decreased ammoniagenesis => metabolic acidosis - natriuresis (via inhibition of proximal Na+ reabsorption)