The document discusses potassium imbalance, focusing on hypokalemia and hyperkalemia, their causes, clinical effects, and treatment approaches. It provides details on potassium distribution and regulation in the body, factors that influence potassium levels, signs and symptoms of imbalance, and strategies for correcting deficiencies and excesses. The document is intended as an educational reference for medical professionals on electrolyte disorders related to potassium.

1. Seminar on
ELECTROLYTE IMBALANCE
: POTASSIUM
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495
References :
1. Harrison’s Principles of Internal Medicine 16th edn.
2. The ICU Book – Paul L Marino.
3. Practical Guide line on fluid therapy – Dr. S. Pandya

2. POTASSIUM BALANCE
 Potassium is the major intracellular cation.
The normal plasma potassium concentration
is 3.5-5.0 mmol/L, whereas that inside the
cells is about 150 mmol/L. The extra
cellular : intracellular ratio being 38 : 1.
 Therefore the amount of K+ in ECF (30-70
mmol) constitutes less than 2% of total body
K+ content (2500-4500 mmol).

3. FACTORS AFFECTING DISTRIBUTION
OF K+ IN AND OUT OF CELL
 Hormones
- Insulin
- Catecholamines
- β2 adrenergic agonist
- α adrenergic agonist
 Acid base balance
- Metabolic acidosis
- Metabolic alkalosis
 Cell turnover.
 Osmolality - in hyperosmolal states K+ diffuses out
of cell along with water due to solvent drag.

4. TOTAL DIETARY POTASSIUM INTAKE
 Total dietary intake of K+ is 40-120 mmol/day
or 1 mmol/kg/day.
 90% of it is absorbed in GI tract
 Sudden rise in plasma K+ is prevented by :
a) Shift of K+ into the cell by insulin.
b) Excess K+ excreted in urine.

5. POTASSIUM EXCRETION
 Renal excretion is the major route for elimination of
dietary and other sources of K+ excess.
 The filtered load of potassium (GFR x plasma
potassium concentration) = (180 L/d x 4 mmol/L =
720 mmol/day) is 10 to 20 fold greater than ECF
potassium content.
 90% of filtered potassium is absorbed in proximal
convoluted tubule. It is absorbed passively with
sodium and water.
 Na+ K+ 2 Cl- cotransporter mediates K+ uptake in
thick ascending limb of loop of Henle.
Contd….

6. POTASSIUM EXCRETION Contd….
 The cell responsible for K+ secretion in late distal
convoluted tubule and cortical collecting duct is the
principal cell, the driving force being favourable electro
chemical gradient across the luminal membrane of the
principal cell.
 The electrical gradient is created by electrogenic Na+
absorption leading to lumen negative trans epithelial
potential difference (TEPD).
 The adults uptake of Na+ by principal cell occurs via
apical Na+ channel and is driven by low intracellular Na+
concentration relative to lumen of CCD.
 The mechanism of transport of Cl- in distal nephron is less
clear.
Contd….

7. POTASSIUM EXCRETION
 The cell responsible for K+ secretion in late distal
convoluted tubule and cortical collecting duct is the
principal cell, the driving force being favourable electro
chemical gradient across the luminal membrane of the
principal cell.
 The electrical gradient is created by electrogenic Na+
absorption leading to lumen negative trans epithelial
potential difference (TEPD).
 The adults uptake of Na+ by principal cell occurs via
apical Na+ channel and is driven by low intracellular Na+
concentration relative to lumen of CCD.
 The mechanism of transport of Cl- in distal nephron is less
clear.
Contd….

8. HYPOKALEMIA
 It is potassium concentration less than 3.5 mmol/L.
CAUSES :
1. Deceased intake
a) Starvation
b) Clay ingestion (geophagia) – it binds dietary K+ and
iron.
2. Redistribution into cell
A) Metabolic alkalosis – due to K+ redistribution into the
cell as well as increased K+ loss (renal).
B) Hormonal
1. Insulin
2. β2 adrenergic agonist – it causes K+ influx into
the cell as well as stimulates insulin release. Contd..

9. CAUSES
C) Anabolic States
1. Vitamin β12 or folic acid (red blood cell
production).
2. Granulocyte macrophage colony stimulating
factor.
3. Total parenteral nutriton
D. Others
1. Pseudohypokalemia
2. Barium toxicity
3. Hypothermia
4. Hypokalemic periodic paralysis.
Contd….

10. CAUSES
3. Increased loss
A. Nonrenal
1. Gastrointestinal
a) Diarrhoea b) Vomiting
2. Integumentary
B. Renal : Increased distal flow
a) Diuretic b) Osmotic diuretic
c) Salt westing nephropathy.
C. Increased renal secretion of K+
a) Mineralocorticoid excess
1. Primary hyper aldosteronism
- Adenoma (Conn’s syndrome)
- Hyperplasia.
- Carcinoma.
Contd….

11. CAUSES
2. Secondary hyperaldosteronism
Malignant Renal artery Renin secreting Hypovolemia
hypertension stenosis tumors
3. Apparent mineralo corticoid excess.
liquorice Chewing tobacco Carbenoxolone Na+
4. Congenital adrenal hyperplasia.
5. Cushing syndrome
6. Bartter’s syndrome.
b. Distal delivery of non-reabsorbed anion :
- Vomiting, nasogastric suction, type 2 (proximal) RTA,
Toluene abuse, penicillin derivatives.
 Others
- Amphotericin B - Liddle’s syndrome - Hypomagnesemia

12. LIDDLE’S SYNDROME
 Autosomal dominant mode of inheritance.
 Hypertension
 Hypokalemia
 Metabolic alkalosis
 Renal K+ wasting.
 Suppressed renin and aldosterone secretion.
BARTTER’S SYNDROME
 ECF volume contraction
 Juxtaglomerular hyperplasia.
 Hyperreninemic hyperaldosteronism.
 Hypokalemia
 Metabolic alkalosis.

13. EFFECT OF HYPOKALEMIA AND
THEIR CLINICAL FEATURES
 The clinical manifestations of potassium depletion vary
greatly between individual patients and their severity
depends on the degree of hypokalemia. Symptoms seldom
occur unless the plasma potassium concentration is <3
mmol/L.
1. Neuro muscular
a. Skeletal muscle weakness :
- fatigue
- Myalgia
- Muscular weakness in lower extremities –
Complete paralysis.
b. Smooth muscles – paralytic ileus.
c. Respiratory muscle weakness – hypoventilation.
d. Tetany
e. Rhabdomyolysis
Contd..

14. EFFECT OF HYPOKALEMIA AND
THEIR CLINICAL FEATURES
2. Renal
- Poly urea (Nephrogenic) diabetic insipidus.
- Increased ammonia production.
- Increased bicarbonate reabsorption.
3. Hormonal
- Decreased insulin secretion.
- Decreased aldosterone secretion.
- Insulin resistance.
4. Metabolic
- Negative nitrogen balance
- Encephalopathy in patients with liver diseae.
5. Cardio Vascular
- ECG changes/dysrrhythmia
- Myocardial dysfunction

15. ELECTROCARDIOGRAPHIC FEATURES OF
HYPOKALEMIA
 The electro cardiographic chanes of hypokalemia are due to
delayed ventricular, repolarisation and do not correlate well
with plasma potassium concentration.
 Early changes include
1. Flattening or inversion of the T wave
2. Prominent U wave
3. ST segment depression
4. Proloned Q.U. interval
 Severe potassium depletion may result in
1. Prolonged PR interval
2. Decreased voltage and widening of the QRS complex
3. An increased risk of centricular, arrhythmias especially
in patients with myocardial ischemia or left ventricular
hypertrophy.

16. CLINICAL APPROACH
HYPOKALEMIA
- Careful hisotry e.g. diuretic & laxative abuse, vomiting.
- exclude pseudo hypokalemia e.g. with marked leuko
cytosis (AML) and normokalemia patients with low
plasma K+ (It is due to WBC uptake of K+ at room
temperature.
- eliminate decrease intake (e.g. starvation, geophagia) and
intracellular cause (e.g. metabolic alkalosis, insulin
therapy, beta 2 agonist administration stress,
hypokalemic periodic paralysis, ananbolic states,
massive transfusion
- Asssess urinary excretion (to clarify source of K+ loss)
* The appropirate response at K+ depletion is to excrete less than 15 mmol/day of
K+ in the urine – due to increased reabsorption and decrease distal secretion.

17. TRANSTUBULAR POTASSIUM
GRADIENT OR TTKG
 This is ratio of K+ concentration in lumen of
cortical collecting duct (CCD) to that of potassium
concentration in plasma.
K+ [CCD] K+(u) ÷ osm (u) /osm (p)
 TTKG = ------------- = --------------------------------
K+ [P] K+ [P]

18. URIANRY K+ EXCRETION
<15 mmol/day >15 mmol/day
Acid base status Assess K+ secretion
Metabolic acidosis Metabolic alkalosis TTKG>4 TTKG<2
• Remoted diuretic use. Acid base • Na waisting
Lower GIT K+ loss • Remote vomiting. nephropathy
status • Osmotic diuresis
• K+ loss via sweating
• Diuresis
Metabolic acidosis Metabolic alkalosis
• Diabetic ketoacidosis
• Proximal type 2 RTA Hypertension
• Distal type-1 RTA
• Amphotericin-B No
Yes
• Vomiting
• Mineralocorticoid excess • Bartter’s syndrome
• Liddle’s syndrome • Exclude diuretic abuse
• Hypo magnesemia

19. TREATMENT
 The therapeutic goals are to correct the potassium deficit and to
minimize ongoing losses.
 It is generally safer to correct hypokalemia via oral route.
 A decrement of 1 mmol/L in the plasma potassium concentration
(from 4.0 to 3.0 mmol/L) may represent a total body potassium
deficit of 200 to 400 mmol.
 For every 1 mmol/L potassium depletion – A potassium deficiency
is = 10% of total body potassium stores (2500-4500 mmol).
 Patients with plasma levels under <3mmol often require in excess
of 600 mmol of potassium to correct the deficit.
 Patients with severe hypokalemia or those unable to take anything
by mouth require intra venous replacement therapy with Kcl
(Potassium chloride).
 The maximum concentration of administered potassium should be
no more than 40 mmol/L via a peripheral vein or 60 mmol/L via
central vein.
 The rate of infusion should not exceed 20 mmol/hr unless paralysis
or malignant ventricular arrhythmia are present.

20. HYPERKALEMIA
 Defined as a plasma potassium >5.0 mmol/L occurs as a
result of either potassium release from cells or decreased
renal loss.
 Iatroenic hyperkalemia may result from over zealous
parenteral potassium replacement or in a patients with
renal insufficiency.
 Pseudohyperkalemia
- Represents an artificially elevated plasma potassium
concentration due to potassium movement out of cells
immediately prior to a following venipuncture,
contributing factors include prologned use of a tourniquet
with or without repeated fist cleneching, haemolysis and
marked leukocytosis or thrombocytosis.

21. CAUSES OF HYPERKALEMIA
 Renal failure
 Decreased distal flow (i.e. decreased effective circulatory arterial
volume.
 Decrease K+ potassium secretion.
A) Impaired Na+ reabsorption
1. Primary hypoaldosteronism
a) Adrenal insufficiency
b) Adrenal enzyme deficiency : 21-hydroxylase, 3 β
hydroxysteroid dehydrogenase, corticosterone
methyl oxidase.
2. Secondary hypoaldosteronism
Hyporeninemia
Drus (ACE inhibitors, NSAIDs, Heparin)
3. Resistance to aldosterone
Pseudohypoaldosteronism
Drus (K+ sparing diuretics, trimethoprim, pentamidine)
B) Enhanced Cl- reabsorption
1. Gordon’s syndrome
2. Cyclosporine

22. CAUSES OF HYPERKALEMIA
C) Shift of potassium out of cell
1. Tissue damage (ischemia or shock) severe exercise.
2. Metabolic acidosis.
3. Uncontrolled diabetes due to insulin deficiency.
4. Aldosterone deficiency.
5. Hyperkalemic periodic paralysis, succinyl choline.
D) Tissue breakdown
1. Bleeding into soft tissue, GI tract or body cavities.
2. Haemolysis, rhabdomyolysis
3. Catabolic state

23. GORDON’S SYNDROME
 Rare condition.
 Characterised by hyperkalemia/metabolic acidosis.
 Normal GFR.
 Volume expansion.
 Suppressed renin and aldosterone levels.
HYPERKALEMIC PERIODIC
PARALYSIS
 Rare autosomal dominant disorder.
 Characterised by episodic weakness or paralysis
precipitated by stimuli that lead to mild
hyperkalemia e.g. exercise.

24. CLINICAL FEATURES
 Hyperkalemia is often asymptomatic until plasma K+
concnetration is >6.5 to 7.0 mEq/L and may lead to fatal
cardiac arrhythmia hence it is called as silent Killer.
 Vague muscular weakness is usually first symptom of
hyperkalemia.
 Severe hyperkalemia can lead to hyporeflexia, gradual
paralysis effecting initially legs then trunk and arms and at
last face and respiratory muscle.
Leg  Trunk Arms Face  Respiratory
 Paralysis usually spares the muscles supplied by cranial
nerves and patients remain alert and apprehensive until
cardiac arrest and death occurs.
Contd….

25. CLINICAL FEATURES
 The most serious effect of hyperkalemia is cardiac
toxicity, which does not correlate well with plasma
potasium concentration.
 The earliest electrocardio graphic changes – include
increased T. wave amplitude or peaked T wave.
Serum K+ ECG findings
6-7 mEq/L Tall peaked T waves
7-8 mEq/L Loss of P waves and progressive widening of
QRS complex.
8-10 mEq/L QRS merges with T waves forming sine waves
> 9 mEq/L Antrioventricular dissociation, ventricular
tachycardia or fibrilation or asystole.

26. DIANGOSIS
 With rare exception, chronic hyperkalemia is always due to
impaired potassium excretion. If the etiology is not readily
apparent and the patients is asymptomatic – pseudohyperkalemia
should be excluded.
 Oliguric acute renal failure and severe chronic renal insufficiency
should be ruled out.
 History should focus on medications that impair potassium
handling and potential sources of potassium intake Evaluation of
the Ecf compartment, effective circulatory volume and urine
output are essential components of the physical examination.
 The severity of hyperkalemia is determined by the symptoms,
plasma potassium concentration and ECG abnormaliteis.
 The appropriate renal response to hyperkalemia is to excrete at
least 200 mmol of potassium daily. In most cases diminished renal
potassium loss is due to impaired potassium secretion, which can
be assessed by measuring the trans tubular potassium
concentration gradient (TTKG).

27. APPROACH TO HYPERKALEMIA
 Exclude pseudohyperkalemia.
 Exclude transcellular K+ shift.
 Exclude oliguric renal failure.
 Stop NSAIDS and ACE inhibitors.
Assess K+ secretion
TTKG<5 TTKG>10 increased distal flow
• Decreased effective circulatory volume.
Response to 9-α Fludro-cortisone • low protein diet [decreased urea]
TTKG>10 TTKG<10
Primary or secondary • Hypotension • Hypertension.
hypoaldosteronism • High renin and aldosterone • Low renin aldosterone
Measure renin and • Pseudohypoaldosteronism • Gordon’s syndrome
aldosterone levels • K+ sparing diuretics • Cyclosporine
• Trimethoprim • Distal type IV RTA
• Pentamidine

28. TREATMENT
 The need to treat hyperkalemia, how urgently and how
aggressively, depends on its degree clinical status.
EMERGENCY TREATMENT.
 Potentially fatal hyperkalemia (serum potassium >7.5
mmol/L).
 Profound weakness, absence of P wave, QRS widening or
ventricular arrhythmia on ECG needs urgent treatment.
 It is based on following principle :
A) antagonism of membrane effects hyperkalemia – Inj.
Calcium gluconate.
B) Potasium movements into the cells – inj. Insulin and
glucose.
- Inj. sodium bicarbonate.
- beta 2 adernergic agonsit salbonate.
C) Removal of potassium from the body
- Loop or thiazide diuretics

29. CALCIUM GLUCONATE
 Calcium gluconate injection is available as 10% solution in
10 ml ampules.
 The usual dose is 10-20 ml infused over 5 to 10 minutes.
 It is the most rapid treatment available and effect begins
within minutes but is short lived 30-60 minutes. The dose
can be repeated if no changes in ECG is seen after 5-10
minutes.
 Calcium administered decreases membrane excitability and
protects the myocardium from toxicity due to potassium.
 It should be remembered that calcium does not lower serum
potassium level, so definite treatment should be planned.
 Calcium can exacerbate or precipitate digitalis induced
arrhythmia. As a result calcium should be avoided if patient
is on digitalis therapy or if necessary should be used with
great care.

30. INSULIN & GLUCOSE
 Fast way to lower serum potassium.
 Insulin causes potassium to shift into cells. Glucose is
administered with insulin to prevent hypoglycemia.
 Administer 25 to 50 gms of glucose together with 10-20
units of regular insulin.
 Dose of insulin is reduced to 50% in a patient with severe
renal impairment.
 Initial bolus of glucose insulin should be followed by
infusion of 5% dextrose at 100 ml/hr to prevent late
hypolycemia.
 If effective, the plasma potassium concentration will fall by
0.5 to 1.5 mmol/L. This effect begins in 15 minutes peaks at
60 minutes and may last for approximately 4-6 hours.
Contd….

31. SODIUM BICARBONATE INFUSION
 Alkali therapy with I/V NaHCO3 will shift potassium into the
cells. Sodium bicarbonate 7.5%, 50-100 ml (45-90 mEq) is
given as bolus I/V slowly over 10-20 minutes followed by
I/VNaHCO3 drip – (3 amp in 1 Lt. NS) and ideally should be
reserved for severe hyperkalemia associated with metabolic
acidosis.
 Onset of its effect is 5-10 minutes and effect lasts for 1-2 hours.
The injudicious use of large amount of alkali can cause
excessive calcium binding to albumin and provokes tetany.
 Care should be taken to avoid contact between calcium
gluconate and soda bicarbonate in the needle, syringe or
infusion set – as it will precipirate into chalky deposits.
 The patients with CRF –ESRD seldomn respond to this therapy
and may not tolerate the sodium load and the resultant volume
expansion.
Contd….

32. BETA ADRENERGIC AGONISTS
 Beta 2 agonist such as salbutamol – promote cellular uptake
of potassium and effectively lower serum potassium level.
 Salbutamol is given in a nebulized form or parenterally dose
recommended is 20 mg in 4 ml of salin by nasal inhalation
ove 10 minutes or 0.5 mg by I/V infusion.
 It generally becomes effective in 30 to 60 minutes and its
effect – persists for 2 to 4 hours. It lowers serum potassium
level by 0.5 to 1.5 mEq/L.
 Insulin and beta agonist exert additive effect. I/V salbutamol
is preferred in ESRD required a rapid lowering of serum
potassium. However, nebulisation is preferred in ESRD
patient associated with CAD because heart rate is less
elevated with nebulisation than I/V therapy.
Contd….

33. LOOP & THIAZIDE DIURETICS
 Often in combination therapy may enhance potassium
excretion,if renal function is adequate.
CATION EXCHANGE RESINS
 Cation exchange resins such as sodium polystyrene sulphonate
(Key xalate) promote the exchange of sodium for potassium in
GI tract. Each gram binds 1 mEQ of potassium and release 2-3
mEq of sodium.
 When given orally the usual dose is 25-30 gram mixed with
100ml of 20% sorbitol resins and 50 ml of 70% sorbitol mixed
in 150 ml water every 4-6 hours as retention enema. It is
retained for about 60 minutes after which rectum is washed
with clear water. The rectal route is faster and more reliable.
 Each enema can generally lower the plasma potassium
concentration by 0.5 to 1.0 mEq/L within 1-2 hours and effect
will last for 4-6 hours.
Contd….

34. DIALYSIS
 The most rapid and effective way of lowering
the plasma potassium concentration is
haemodialysis (removal rate 35 mEq/hour).
 Dialysis should be reserved for patient with
renal failure and those with severe life
threatening hyperkalemia unresponsive to
more conservative measures.
 Peritoneal dialysis also removes potassium
but is only 15-20% as effective as
haemodialysis.

35. NON EMERGENCY TREATMENT
 (Mild to moderate hyperkalemia)
1. DIETARY POTASSIUM RESTRICTION
- Avoid fruit juice, coconut water and food rich
in potassium.
2. AVOID MEDICATION
- Potassium sparing diuretics, NSAIDS and
ACE inhibitors (all decreased potassium
excretion).
- Beta blockers (decrease ECF to ICF shift of
potassium).
3. LOOP OR THIAZIDE DIURETICS
- increased renal excretion of potassium.

36. 4. Cation exchange resins
- dose required 15-20 gm keyxalate, 2-4 times/day.
5. Specific etiological treatmetn
- Addison’s disease – glucocorticoid (hydro cortison)
therapy.
- Hypoaldosteronism : mineralocorticoid supplement
0.2 mg/day (Fludrocortisone).
- Hyperkalemia periodic paralysis – prophylactics beta
2 agonsit inhalation.
- Treatment of diabetic ketoacidosis.
- Correct volume depletion.
- Correct metabolic acidosis. Metabolic acidosis is
generally associated with hyperkalemia so treat with
soda Bicarb (600 tab. 2-3 times per day) or sodium
citrate (Shohl’s solution 10-15 ml TDS).