Hypokalaemia By Dr Nihal Abosaif Consultant acute physician UHCW

Outline Physiology of K+ transport Factors modifying transcellular K+ distribution Causes of Hypokalaemia Diseases associated with it Management of Hypokalaemia

Most abundant cation in human body Regulates intracellular enzyme function and helps to determine neuromuscular & cardiovascular tissue excitability. 90 % of total body K+ : Intracellular ( predominantly in muscle ) 10 % : Extracellular fluid < 1 % : Plasma Introduction : Potassium

Ratio of extracellular K+ to Intracellular K+ : determines the membrane potential The acuity of changes in serum potassium concentration & membrane potential determines clinical symptoms and underlying signs Plasma concentration varies from 3.5 to 5.3 mmol/l Introduction : Potassium

K+ uptake into cells : actively driven by Na+/K+/ATPase Leak back into ECF : opposed by electrical gradient Physiology Of Potassium Homeostasis

Acid base status Pancreatic hormones : insulin, glucagon Catecholamines Aldosterone Plasma Osmolality Exercise Cellular K+ content Factors modifying transcellular K+ distribution

Alkalosis promotes K+ uptake by cells Acidosis diminishes K+ uptake by cells Acute respiratory alkalosis, in contrast increase plasma K+ by 0.2 mmol/l per 0.1 pH unit due to increased adrenergic activity Acid Base Status

Insulin stimulates cellular uptake of K+ by activating Na+/K+/ATPase ( decreasing plasma K+ ) Insulin affects K+ transport independently of glucose uptake Glucagon increase plasma K+ independently of changes in plasma glucose / insulin Pancreatic Hormones

Beta 2 adrenergic activity – hypokalaemia Alpha adrenergic antagonists – hypokalaemia Catecholamines

Invitro studies Aldosterone stimulates Na+/K+/ATPase and thereby activating Na + influx Aldosterone

Hyperosmolality ( Mannitol infusion / hyperglycemia in DM ) : increase plasma K+ Each 10 mOsm / Kg rise in plasma osmolality, increases plasma K+ by 0.6 mmol/l Osmolality

Recurrent contraction increases K+ egress from muscle Modest exercise : high K+ in ECF in local environment produces vasodilatation & thereby increased regional blood flow Severe exercise : increase plasma K+ modestly Physical training increases Na+/K+/ATPase activity in skeletal muscle which helps skeletal muscle to take up K+ again Exercise

Kidney is dominant in sustaining K+ balance >90 % K+ : excreted in urine Remainder through faeces Decrease in GFR, K+ excretion via faeces increased GI Loss : K+ secretion by proximal & distal colon K+ Balance

Renal Handling of K+ Glomerulus: freely filtered PCT, TAL, Loop of Henle : reabsorbed

Defined as plasma concentration of K+ < 3.5 mEq/L Mild Hypokalemia : 3.0 – 3.5 mEq/L : asymptomatic Hypokalemia < 3.0 mEq/L : symptomatic Clinical manifestations of hypokalemia vary greatly between individual patients & their severity depends on degree of hypokalemia Hypokalemia

Clinical features Investigations Diagnosis

Mild hypokalemia : generally asymptomatic Increased risk of mortality for pts with cardiovascular disease – trigger ventricular tachycardia / ventricular fibrillation (decrease K+ : d/t sympathetic stimulation) Digitalis induced arrhythmias – can occur with normal drug levels if hypokalemia is present Diuretic induced hypokalemia & hypomagnesemia must be avoided in pts on drugs that prolong QT interval : as it predisposes to polymorphic VT / Torsade de pointes Hypokalemia < 3 mEq/L : Symptomatic Clinical Features

Digitalis Intoxication : ventricular extrasystoles ventricular tachycardia ventricular fibrillation partial-complete AV block bradycardia atrial flutter atrial fibrillation Ventricular arrhythmias : tachycardia / fibrillation Cardiac

Fatigue Myalgia Muscular weakness involving lower limbs Severe Hypokalemia : Paralysis ( extremities ) Weakness of respiratory muscles ( dyspnea ) Rhabdomyolysis (exercise induced) Neuro-muscular

Constipation Paralytic ileus Gastro-intestinal

Chronic interstitial nephritis due to functional decrease in renal blood flow – decreased GFR Chronic renal failure Renal Cysts Renal

Polyuria ( nephrogenic diabetes insipidus ) Polydipsia ( nephrogenic diabetes insipidus ) Increased ammonia production ( intracellular acidosis ) precipitate hepatic coma in pts with advanced liver ds Edema Chloride wasting Metabolic alkalosis Hypercalciuria Phosphaturia Fluid – Electrolyte

Glucose intolerance ( decreased insulin secretion ) Growth retardation ( Reduced Growth hormone receptors, Reduced IGF-1 ) Hypertension ( increased renin secretion ) Endocrine

ECG : Initially : flattening of t wave depression of ST Segment development of prominent u waves Severe hypokalemia : increased amplitude of p wave increased QRS duration S.Potassium Basic Investigations

Investigations – Causes Urinary K+ TTKG Urinary Chloride CBC Peripheral Smear ABG Echocardiogram Cardiac Enzymes Serum aldosterone Serum renin USG Abdomen CT / MRI Abdomen FBS / PPBS / Urine Ketones TSH / free T3 / free T4 Colonoscopy / OGDscopy

 Decreased net intake  Shift into cells  Increased net loss Causes of hypokalaemia

Decreased total body K+ Decreased intake Renal loss of K+ Extra renal loss of K+

Occurs in patients with extreme leukocytosis eg : in myeloproliferative disorders Invitro WBC uptake potassium within the test tube Spurious Hypokalemia

Starvation Clay ingestion ( binds to dietary K+ & Iron ) Diarrhoea and vomiting Decreased Intake or increased loss

Acid – Base Status : Metabolic Alkalosis Hormonal : Increased Insulin Increased Beta 2 Adrenergic activity Drugs : Beta 2 agonists Theophylline Barium Intoxication Chloroquine Calcium Channel Blockers Transcellular shifts

Catecholamine release associated with :  Asthma  COPD – exacerbations  Heart failure  Myocardial infarction / angina  Drug withdrawal syndrome – alcohol / narcotics / barbiturates Transcellular shift

Insulin administration – for treatment of DKA Refeeding Syndrome Hypokalemic Periodic Paralysis Thyrotoxic Periodic Paralysis Treatment of anemia : Vit B12 / Folic acid deficiency Use of GM – CSF in patients with Neutropenia Transcellular shift

Urinary K+: > 20 mEq/L – Renal loss Urinary K + : < 20 mEq/L – Extrarenal loss TTKG : Transtubular Potassium Gradient ( Urine K+ / Plasma K+ ) ( Urine Osm / Plasma Osm ) TTKG : Renal loss : > 4 Extra renal loss : < 4 Renal Vs Extra renal loss

Algorithm for diagnosis of Extra Renal Loss Urinary K+ < 20 mEq/L Metabolic Acidosis GI Loss Diarrhoea Laxative Abuse Normal pH Villous Adenoma Laxative Abuse Metabolic Alkalosis GI Loss: rare Laxative abuse : rare

Urinary loss K+ > 20 mEq/L Metabolic Acidosis RTA DKA Ureterosigmoido stomy Variable pH ATN recovery Post obstructive diuresis Drugs Metabolic Alkalosis Urinary chloride level Renal Loss

Urinary Chloride < 20 mmol/L Diuretics Vomiting > 20 mmol/L Check BP Renal Loss + Metabolic Alkalosis

Check BP, ECFLow BPCheck Bicarb Low - RTAHigh : Bartter, Gitelman HTN, Increased ECF Check Renin, Aldosterone Renal loss +Urine Cl > 20 mEq/L

Amphotericin B : tubular damage increased excretion of K+ Aminoglycosides : renal wasting of K+ Thiazides, Furosemide, Acetazolamide : renal loss K+ Cisplatin HYPOMAGNESEMIA : Significant renal K+ wasting Renal loss - Drugs

Management of Hypokalaemia If mild asymptomatic Oral KCl If severe or symptomatic hypokalemia IV KCl supplement

IV infusion rate for severe or symptomatic hypokalemia. Standard IV replacement rate mmol/h Serum potassium < 2.5 meq/L, or Moderate-severe symptoms mmol/h Serum potassium < 2.0 Meq/L, or Life-threatening symptoms > 40 mmol/h If heart block, or Renal insufficiency exists mmol/h

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