disorders of potassium dr muhammad rizwan ul haque assisstant professor of nephrology shaikh zayed...

Disorders of potassium

Dr Muhammad Rizwan ul Haque

Assisstant Professor of NephrologyShaikh Zayed Postgraduate Medical

instituteLahore

Potassium Functions

Most abundant intracellular cation Regulates heart function Essential for protein and nucleic

acid synthesis Important for neuromuscular

excitability Maintains resting membrane

potential

Potassium Metabolism

• Normal potassium level is 3.5-5.0 mEq/L

• Poor indicator of total body stores• Total body potassium stores are

approximately 50 mEq/kg (3500 mEq in a 70-kg person).

Serum Potassium Regulation

Well-developed systems for sensing potassium by the pancreas and adrenal glands High serum potassium - insulin –

stimulation of sodium potassium pump in muscles - muscle uptake of potassium

aldosterone- enhancement of distal renal expression of secretory potassium channels (ROMK) – potassium excretion

Serum Potassium Regulation

Low potassium states result in insulin resistance, impairing

potassium uptake into muscle cells cause decreased aldosterone release

leading to decrease renal potassium excretion

Potassium Metabolism

88-90 %

2-3 %

9-10%

In Renal Failure

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

K+K+

K+

-35

-60

SA Node Action Potential

Threshold Potential

Resting MembranePotential

Excitability Potential

Normal Cardiac Tissue Excitability

- 90

- 60

+20

0

Nernst Equation

Ex = - x log 61Z

Xi

Xo

Resting membrane potential is the combination of equilibrium potential and conductance of various ions

Equilibrium Potential

Equilibrium PotentialNernst Equation

96-(134+52)=-90 mv

Disorders of Potassium

• Hyperkalemia• Intake > Excretion (loss)

• Transcellular shift

• Hypokalemia• Excretion (loss) > Intake

• Transcellular shift

Renal Excretion of Potassium

Renal adaptive mechanisms allow the kidneys to maintain potassium homeostasis until the GFR drops to less than 15-20 mL/min

Obligatory renal losses are 10-15 mEq/day. 

Increased Renal Excretion

Aldosterone High distal delivery of sodium

(diuretics) High urine flow rate (osmotic

diuresis) High serum potassium Delivery of non-absorbable anions to

collecting duct. (bicarbonate)

Decreased Renal Excretion

Aldosterone deficiency or resistance to aldosterone

Low distal delivery of sodium Low urine flow rate Low serum potassium Renal failure

Trans-cellulr shift Glucoregulatory hormones

Insulin enhances potassium entry into cells, Glucagon impairs potassium entry into cells

Adrenergic stimuli: Beta-adrenergic stimuli enhance potassium entry

into cells Alpha-adrenergic stimuli impair potassium entry into

cells pH:

Alkalosis enhances potassium entry into cells Acidosis impairs potassium entry into cells

Transcellular Potassium Shift

• Insulin• Beta-adrenergic stimuli• Alkalemia• Blood at higher temp

• Glucagon• Beta blockers• Alpha adrnerigic stimulation

• Tissue destruction• Acidemia• Acute increase in serum osmolility• Blood stored at <4 Co

K+

K+

K+

K+

K+

K+K+

K+

K+

K+

K+

K+

K+

K+

K+

K+

HYPOKALEMIAHYPERKALEMIA

Hyperkalemia

5 % in general population 10 % of hospitalized patients

Classification of Hyperkalemia

5.5-6.0 mEq/L – Mild Hyperkalemia 6.1-7.0 mEq/L - Moderate 7.0 mEq/L and greater - Severe

Mortality

Overall mortality rate 14.3%. The risk increasing as the potassium level increases.

Serum Potassium Mortality rate

7 meq/l 28 %<6.5 meq/l 9 %

Causes of Hyperkalemia

For excessive potassium intake, Eating disorders - exclusively high-potassium

foods, such as fruits, dried fruits, juices, and vegetables with little to no sodium

Heart healthy diets - Very low–sodium and high-potassium diets

Use of potassium supplements in over-the-counter herbal supplements, salt substitutes, or prescribed pharmacologic agents

Causes of Hyperkalemia

• Renal failure• Ingestion of drugs that interfere with

potassium excretion • Potassium-sparing diuretics,• Angiotensin-converting enzyme inhibitors,• Nonsteroidal anti-inflammatory drugs,

• Impaired responsiveness of the distal tubule to aldosterone• Type IV renal tubular acidosis observed

with diabetes mellitus, sickle cell disease.• Chronic partial urinary tract obstruction

Causes of Hyperkalemia Hyperosmolality Rhabdomyolysis  Tumor lysis syndrome Succinylcholine administration, which

depolarizes the cell membrane EACA (Epsilon aminocapric acd), arginine and

lysine administration Hyperkalemic periodic paralysis Insulin deficiency or insulin resistance (ie, type

I or type II diabetes mellitus) Use of beta-adrenergic antagonist therapy (eg,

for hypertension or angina

Pseudohyperkalemia

Prolonged use of tourniquet Hemolysis (in vitro) Delay in processing of blood Severe leukocytosis Severe thrombocytosis

Symptoms

Nonspecific, related to muscular or cardiac function.

Weakness and fatigue. Occasionally, frank muscle

paralysis or shortness of breath. May be palpitations or chest pain.

Hyperkalemia- Signs

Bradycardia due to heart block or tachypnea due to respiratory muscle weakness.

Muscle weakness and flaccid paralysis

Depressed or absent deep tendon reflexes

Muscle tenderness, weakness, suggesting rhabdomyolysis.

ECG in Hyperkalemia

Threshold Potential

Resting MembranePotential

Excitability Potential

Normal Cardiac Tissue Excitability

- 90

- 60

+20

0

Threshold Potential

Resting MembranePotential

Excitability Potential

Increased Excitability

- 60

- 70

- 90

Threshold Potential

Resting MembranePotential

Excitability Potential

Persistent Depolarization in Hyperkalemia

Work-up Urinary potassium, serum sodium, urine

osmolality Transtubular potassium gradient = (urine K x serum osmolarity)/(serum K x urine

osmolarity) TTKG of < 3 - lack of aldosterone effect

on collecting tubules – decreased excretion

TTKG greater > 7 - an aldosterone effect, - normal excretion

24 hour urinary potassium.

Transtubular Potassium Gradient (TTKG)

It is a measurement of net K+ secretion by the distal nephron after correcting for changes in urinary osmolality

Determine whether hyperkalemia is caused by Aldosterone deficiency/resistance

or Nonrenal causes.

Clinical correlation and potassium intake should be assessed.

TTKG = (Ku/Ks) × (Sosm/Uosm)

Transtubular Potassium Gradient

Evaluation of Hyperkalemisa

Emergently treat K+

Are K sparing medications are being administered

Are ECG changes are present

Treatment

Evaluation for potential toxicities Decreasing potassium intake Increasing potassium uptake into

cells Increasing potassium excretion Determining the cause to prevent

future episodes

Treatment of HyperkalemiaDrug Route of

Admin.Onset Duration

Calcium IV 10 cc 10% 1-3 min 30 min

Insulin- Glucose

IV 20-30 minutes

2 hours

Beta adrenergic

20 mg in 4 ml nebulize in 10 m

15-30 min 30 min- 3 hrs

Ion exchange resins

15 G in 15-30 ml 70% sorbitol

2-6 hrs 6-12 hrs

Diuretics IV 40-80 mg Furosemide

15 min 2-3 hours

Hemodialysis Immediate

Until dialysis completed

Threshold Potential

Resting MembranePotential

Excitability Potential

Normal Cardiac Tissue Excitability – Effect of Calcium

- 90

- 60

High Serum Calcium

Threshold Potential

Resting MembranePotential

Excitability Potential

Increased Excitability

- 60

- 90

- 30

Threshold Potential

Resting MembranePotential

Excitability Potential

Increased Excitability- Effect of Calcium

-60

- 70

-90

-40

30

1030

Hypokalemia

Hypokalemia

Defined as a potassium level less than 3.5 mEq/L.

Mild hypokalemia - serum level of 3-3.5 mEq/L.

Moderate hypokalemia - serum level of 2.5-3 mEq/L.

Severe hypokalemia - level less than 2.5 mEq/L.

Symptoms Palpitations Skeletal muscle weakness or cramping Paralysis, paresthesias Constipation Nausea or vomiting Abdominal cramping Polyuria, nocturia, or polydipsia Psychosis, delirium, or hallucinations Depression

Signs Signs of ileus Hypotension Ventricular arrhythmias Cardiac arrest Bradycardia or tachycardia Premature atrial or ventricular beats Hypoventilation, respiratory distress Respiratory failure Lethargy or other mental status changes Decreased muscle strength, fasciculations, or

tetany Decreased tendon reflexes

ECG in Hypokalemia

Threshold Potential

Resting MembranePotential

Excitability Potential

Hyperpolarization in Hypokalemia

-120

Causes of Hypokalemia

Medications: Thiazide and loop diuretics,

aminoglycosides, amphotericin B, β2-agonists, and adrenal steroids, Chronic laxative abuse

GI Vomiting, diarrhea, NG suction

Causes of Hypokalemia

Renal: Renal tubular acidosis, (type 1 , 2) Magnesium deficiency Primary hyperaldosteronism Cushing Syndrome Salt-losing nephropathies Bartter and Gitelman syndromes Therapeutic alkalinization of the urine

Causes of Hypokalemia

Treatment of megaloblastic anemia with vitamin B12 and folate

Miscellaneous toxic conditions: Barium intoxication; chloroquine toxicity;

glue sniffing due to hippurate accumulation,

Tocolytic therapy in pregnant women to treat premature labor

Amphotericin B therapy

Causes of Hypokalemia Genetics disorders

Familial (hypokalemic) periodic paralysis Congenital adrenogenital syndromes Liddle syndrome Bartter and Gitelman syndromes Familial interstitial nephritis Glucocorticoid-remediable aldosteronism

Diagnostic Workup of Hypokalemia

Treatment of Hypokalemia

Potassium replacement How much? What route? How fast ? What salt ?

Treatment

Asymptomatic mild hypokalemia Oral replacement

Moderate to severe (no emergency) Intravenous

40 meq/l 160 meq per day

Hypokalemia with cardiac dysarrythmias 20 meq/100 cc /hr under ECG monitoring

Treatment of Hypokalemia

Metabolic alkalosis Potassium chloride

Metabolic acidosis Potassium citrate/acetate

Diabetic ketoacidosis (+hyphosphatemia) Potassium phophate

Threshold Potential

Resting MembranePotential

Excitability Potential

Hyperpolarization in Hypokalemia

-120

Threshold Potential

Resting MembranePotential

Excitability Potential

Hyperpolarization in Hypokalemia

-120

Ca++ administration

Threshold Potential

Resting MembranePotential

Excitability Potential

Low Serum Potassium & Calcium

-120

S. Potassium correction in hypocalcemia

Hypocalcemia

Threshold Potential

Resting MembranePotential

Excitability Potential

Low Serum Potassium & Calcium

-120

S. Calcium correction in hypokalemia

Hypocalcemia