GP SYMPOSIUM 2015 15TH AUGUST 2015 APPROACH TO HYPOKALAEMIA

Dr. Sanjaya Dissanyake Dr. Daphne Lee Division of Endocrinology Khoo Teck Phuat Hospital

Outline • Hypokalaemia • Potassium homeostasis • Causes of hypokalemia • Case discussions • Practical approach to hypokalaemia • Management of hypokalaemia

Hypokalemia: Plasma K < 3.5 mmol/L

• May be asymptomatic • Can result in arrhythmias, rhabdomyolysis, paralysis

• Neuromuscular and cardiac symptoms induced by hypokalaemia are related to alterations in the magnitude of the resting membrane potential which affects the generation of the action potential

• Clinical manifestations determine urgency and magnitude of treatment

Potassium Homeostasis

Causes of Hypokalaemia

Case 1: Mr. ZXJ • 22 year old Chinese man • No past medical history of note • Had large buffet meal for dinner • Now admitted for sudden weakness all 4 limbs • BP 130/80mmHg, HR 120bpm, regular • K 2.2 mmol/L

Examination & Investigations • Tachycardic, sweaty, tremulous • Diffuse goitre with bruit • Bilateral exopthalmos • fT4: 50.1 pmol/L • TSH <0.001 mIU/L • K 2.2 mmol/L • What is the diagnosis?

Thyrotoxic Periodic Paralysis

What would you like to do now? 1. Start oral and IV KCl replacement 5 cycles 2. Do stat ECG 3. Refer to ED 4. Send home with span K 1.2g tds and carbimazole

Hypokalemia: Transcellular Shifts

• Maintenance of potassium in ICF is achieved by the action of the 3Na/2K ATPase pump present on cell membranes • Pumps 3Na out for 2K in • Contributes to generation of resting membrane potential

• Increased activity results in shift of potassium into the cell-> hypokalaemia

Cellular Potassium Shifts

1. Acute increase in hematopoietic cell production

2. Metabolically active blood cells e.g. AML with high WBC,

3. Hypothermia 4. Barium

intoxication

Hypokalaemia in Thyrotoxic Periodic Paralysis is due to Cellular Shifts • Activity of Na/K ATPase is increased by:

• Thyroid hormone • Catecholamines

• Adrenergic activity is increased in hyperthyroidism • Also results in release of insulin from beta cells

• Insulin • Explains why CHO rich meals trigger paralysis

• Administration of potassium • To enable recovery from paralysis and prevent arrthymias • Slow and cautious -> rebound hyperkalaemia

• Occurred in as many as 42% in one series (Manoukian et al 1999)

Case 2. Mr. NNP • 70 year old Chinese man • Past medical history :

• Hypertension • Poorly controlled on 3-4 anti-hypertensives • BP 150/80mmHG

• Referred for persistent hypokalaemia • K 2.5 mmol/L

What further history and investigations will you perform?

History

A. Any symptoms of hypokalemia?

B. Duration of hypertension?

C. Drug history? TCM use? Liquorice? (assam boi)

D. Any GI losses? E. Any features to suggest

Cushings?

Investigations

A. Renal panel B. Magnesium level C. Urine K/Cr ratio D. Aldosterone E. Renin F. Overnight dexamethasone suppression test

Investigations • Na 141 mmol/L (135-145) • K 2.9 mmol/L (3.5-5.1) • Cr 68 umol/L (59-104) • HCO3 29 mmol/L (23-29) • Urea 4.3 mmol/L (2.8-7.6) • Magnesium 0.9 mmol/L (0.8-1.4mmol/L) • pH 7.47 (7.35-7.45) • Urine K >100 mmol/L • Urine Cr 14.6 mmol/L • Urine K/Cr ratio 6.85 (<1.5 mEq/mmol of creatinine)

What is the diagnosis? • Hypertension • Hypokalaemia • Metabolic Alkalosis • Kaliuresis

• Aldosterone 1118 pmol/L (>414 pmol/L) • Renin <0.13 ng/ml/hr • Aldosterone renin ratio 8600 (>555) • Saline Suppression test 434-374 pmol/L (<277 pmol/L)

Primary Hyperaldosteronism

Hypokalaemia + Hypertension

Hypertension and Hypokalaemia

Aldosterone high and renin low

Primary hyperaldosteronism

Aldosterone and renin both raised

Secondary hyperaldosteronism

Aldosterone low and renin low Pseudohyperaldosteronism

Angiotensinogen Angiotensin I Angiotensin II

Aldosterone secretion, arteriolar

vasoconstriction, ADH secretion

Aldosterone causes increased Na retention and

K loss

Renin

Secondary Hyperaldosteronism

Raised renin and aldosterone

Secondary hyperaldosteronism

Renal artery stenosis Co-arctation of the aorta Malignant hypertension Renin producing tumors

Pheochromocytoma

Pseudohyperaldosteronism

Low renin and low aldosterone

Think of other substances that activate

mineralocorticoid receptor

Congenital adrenal hyperplasia

17 α hydroxylase deficiency

11 β hydroxylase deficiency

Cushing’s syndrome

Liddle’s syndrome

Exogenous mineralocorticoid

Licorice ingestion

Apparent mineralocorticoid

excess

How does Cushing’s and Liquorice Cause Hypokalaemia? • Cortisol binds to mineralocorticoid receptor in the kidneys in equal

affinity as aldosterone • However it is normally deactivated by 11β hydroxysteroid

dehydrogenase 2 (11-β HSD 2) to cortisone which is unable to bind to

MC receptor • In Cushing’s the excess cortisol levels overwhelms the capacity of 11-

β HSD -> activation of MC receptors • Liquorice inhibits 11-β HSD 2; inactivating mutation of 11- β HSD2

gene in apparent mineralocorticoid excess

Drugs can affect aldo/renin values

Case 3 • 50 year old Chinese lady • No past medical history of note • Admitted for generalised weakness • Noted K 2.2 mmol/L • On further history:

• Dry eyes and dry mouth x few months • Bloating of the fingers • Raynaud’s phenomenon

Investigations • Na 142 mmol/L • K 2.2 mmol/L • Chloride 118 mmol/L • Creatinine 75 umol/L • Urea 4.0 mmol/L • pH 7.28 • Bicarbonate 13 mmol/L (21-29) • Urine pH 7.0

• What is the diagnosis?

Renal tubular acidosis secondary to Sjogren’s syndrome

Hypokalaemia + Metabolic Acidosis • Renal tubular acidosis

• Type 1 • Type 2

• Treatment of diabetic ketoacidosis • Diarrhea/laxative abuse

Renal Tubular Acidosis • Failure of kidneys to acidify the urine

• Failure to recover bicarbonate in proximal tubule-> Proximal RTA (type 2)

• Insufficient secretion of acid in distal tubule -> Distal RTA (type 1) • Combined -> type 3 RTA

• Results in hyperchloraemic normal anion gap acidosis • Renal sodium wasting is common and results in depletion

of ECF volume and secondary hyperaldosteronism with increased loss of K+ in the urine.

Practical Approach to Hypokalaemia • Evaluate for life threatening consequences of

hypokalaemia • ECG • Examine for weakness

• Exclude hypomagnesemia • Assess for etiology

• Exclude pseudohypokalaemia • Abnormal WBCs • Artifact of storage procedure

• Rapid separation of plasma/storing at 4 deg C confirms diagnosis

• Redistribution vs. Depletion • If depletion: Renal vs. GI losses • Renal losses: think syndromes

Don’t Forget Drugs

Management • Goal of therapy are:

1. Prevent or treat life threatening complications 2. Replace the potassium deficit 3. Diagnose the underlying cause

• Urgency of treatment depends on severity of hypokalaemia, associated/comorbid conditions • Risk of arrhythmia is highest in older patients, patients with heart

disease, patients on digoxin or antiarrhythmic drugs

• Mainstay of treatment is potassium replacement • Stop ongoing losses

How to replace? • Oral preparations:

• Potassium chloride • Potassium phosphate • Potassium bicarbonate • Potassium citrate • Potassium gluconate

• 10mEq will raise K by 0.1mmol/L • 40-100mEq/day • Mist KCL: 15mls contains 20 mEq of

potassium chloride

Preferred choice: 1. patients with hypokalemia and

metabolic alkalosis are often chloride depleted as well which contributes to maintenance of metabolic alkalosis

2. KCL replaces serum K concentration at faster rate

When to refer? • Severe hypokalaemia <2.5 • Symptomatic • Elderly • Patients with heart disease • Chronic hypokalemia with hypertension

THANK YOU The End