Potassium Balance (Renal Pathophysiology) PDF

Renal-II: Potassium Balance (Renal pathophysiology 5th Ed. Chapters 7; Rennke and Denker) Pedro Del Corral, Ph.D. M.D. Associate Professor Department of Physiology & Pathology Burrell College of Osteopathic Medici...

Renal-II: Potassium Balance (Renal pathophysiology 5th Ed. Chapters 7; Rennke and Denker) Pedro Del Corral, Ph.D. M.D. Associate Professor Department of Physiology & Pathology Burrell College of Osteopathic Medicine September 23rd 2024 1 Objectives Explain the factors involved in the regulation of potassium balance, both transcellular distribution & urinary excretion. Discuss the major causes of hyperkalemia with particular emphasis on the importance of impaired urinary potassium excretion in patients with persistent elevations in the plasma potassium concentrations Discuss the physiologic principles that govern the choice of therapies for reversing hyperkalemia Explain the factors that can lower the plasma potassium and the mechanisms by which urinary potassium wasting can occur Describe the pathology, pathophysiology, and clinical manifestations of Syndrome of apparent mineralocorticoid excess, licorice ingestion, Liddle Syndrome, Bartter syndrome, and Gitelman syndrome 2 Case presentation A 49 y.o woman is found to have Plasma & urine tests show: a moderate hypertension that is Na: 140 mEq/L (136-142) known to be of recent onset. She K: 3.1 mEq/L (3.5-5) is on no medication & complains Cl: 98 mEq/L (98-108) only of mild muscle weakness. Total CO2: 32 mEq/L (21-30) Physical examination reveals a Urine blood pressure of 150/110 and Na: 80 mEq/L (variable) proximal muscle weakness is K: 60 mEq mEq/L (variable) noted. Cl: 100mEq/L (variable) 3 Physiologic effects of potassium Total body K is ~ 3,000-4,000 mEq (98% intracellular) Mechanisms of homeostasis Na-K-ATPase pump 3:2 ratio Intracellular & extracellular concentrations Plasma concentration vs intracellular Functions: Protein synthesis, glycogen synthesis, insulin release Membrane potential: Intra/extra ratio Hypokalemia Membrane potential more electronegative→ Na-channels compensate Hyperkalemia Membrane potential less electronegative → ↓Na-channels Changes in K+ concentration can lead to muscle weakness and cardiac arrhythmias Factors: → Magnitude & rate of change 4 Regulation of potassium balance Extracellular volume 12-14L 4-5 mEq/L 50-70 mEq Average K+ intake 40-100 mEq, how do we avoid hyperkalemia? Foods high in K+ ? ↑ cellular uptake Na-K-ATPase pump ↑ Renal excretion 6-8 h 5 Effects of β-adrenergic blockade on plasma potassium 6 Urinary potassium excretion GFR of 180 L/day (125 ml/min) Plasma K ~ 4.5 mEq Filter load of 810 mEq Most passively reabsorbed Proximal tubule Thick ascending loop of Henle Secretion Principal cells in collecting ducts & outer medullary collecting duct ↑Intracellular K+ Na-driven luminal electronegative potential Effects of K+ on aldosterone Na-driven luminal electronegative potential Na-K-ATPase pump ↑Apical K+ channels Hyperkalemia 7  Hyperkalemia Hyperkalemia due to: ↓ cell entry (for acute, not chronic) ↑ cell release ↓reduced urinary excretion K-adaptation Acute vs chronic effects Note K-adaptation Na-K-ATPase of principal cells Hyperkalemia is associated with an impairment in urinary potassium excretion, factors affecting secretion: Hypoaldosteronism ↓ distal urinary flow d/t volume depletion (HF) Etiology of hyperkalemia or advance renal failure 8 Hyperkalemia Metabolic acidosis 9  Etiology of hyperkalemia: metabolic acidosis Metabolic acidosis: ↑H+, Cl major anion has limited entry to cells Na & K come out ~ ↑0.6 mEq/l of K per 0.1 pH unit drop in extracellular pH Exacerbated in chronic renal failure Insulin 10 Etiology of hyperkalemia: Insulin deficiency Uncontrolled diabetes: Insulin deficiency Hyperosmolality (Hyperglycemia) Osmosis Frictional forces (solvent & solute) Aquaporins Can be complicated further by metabolic changes Beta adrenergic blockade 11 Etiology of hyperkalemia: Muscle breakdown-----------Intense/severe Exercise Severe physical trauma Exercise Vasodilatory effect Crushing injuries Why? Delay of K exit during depolarization & reuptake via Na-K-ATPase Rhabdomyolysis ATP sensitive inhibition of potassium channels Effects are dose/duration dependent Can lead to arrhythmias ↓ K+ excretion in the urine 12