HYPERTENSION AND HYPOKALEMIA

Sekhar Chakraborty, Siliguri

INTRODUCTION
Hypertension and Hypokalemia are two distinct clinical entities, whenever present in a single clinical
setting of an individual, may or may not be related to each other. However it is mandatory for a treating
physician to search for this clinical correlation. Detection of the underlying cause not only guides
the treatment protocol but also dictates further steps for prevention of hypertension & hypokalemia,
prevention for life threatening conditions like arrhythmias, sudden cardiac death, respiratory failure
etc. & provides the insights for prognosis. Simple reason like diuretic induced hypokalemia for the
treatment of hypertension may be overshadowed with complicated genetic disorders, channelopathies
or endocrine disorders which need prolonged biochemical & genetic workup. Therefore careful &
vigilant approach is warranted in this clinical setting.
Potassium Homeostasis

Approximately 98 % of total body stores are intracellular

Normal Serum [K+] ranges from 3.5 5 mmol/ L

Insulin, aldosterone, catecholamine & acid base status influence movement of [K+] into the
cells.

K+ excretion is regulated at the distal nephron.

K+ excretion is related to (Urine flow rate)

The marked discrepancy between intracellular & extracellular content of potassium is illustrated Fig. 1.
Total body potassium content in healthy adult is approx 50mEq/ kg, so a 70 kg adult will have 3500
mEq as 2% of total amount is in extracellular fluid, therefore ECF contain 70 mEq K+. As plasma
4000
Total Body K (mEq)

3:5

3000

353500

2000

70 mEq

1000

0
Intracellular Potassium

Extracellular Potassium

Fig. 1 : Intracellular & extracellular content of potassium

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Hypertension and Hypokalemia

accounts for approx 20% of ECF volume, the potassium

content of plasma is about 15 mEq which is about 0.4% of
total body potassium.
This suggests that plasma potassium is an insensitive marker
of changes in total body potassium stores.
Serum level of K+ is regulated by

Uptake of K+ into cells by altering activity of Na KATPs pump in the cell membrane.

Renal excretion mainly controlled by aldosterone.

10
8

(70 kg Adult)

Serum K+
(mEq/ L)
6-

ACIDOSIS

Extra renal loss e.g. gastrointestinal.

Definition of Hypokalemia
Hypokalemia has been defined as Serum [K+] is < 3.5 mEq/
L. Severe hypokalemia where
Serum [K +] = < 2.5 mEq / L (Figs. 3 and 4).
HYPERTENSION
Hypertension, more specifically systemic arterial hypertension
is defined as the elevation of blood pressure (BP) to such a level
that place patients at increased risk of target organ damage
in several vascular beds including the retina, brain, heart,
kidneys and large condict arteries. In demographic studies the
level has been observed above 120/80mHg. Hypertension has
been staged as High normal stage I & II, Hypertensive crisis,
isolated systolic HTN according to level of elevation of BP,
rapidity of development of HTN, threat to vascular bed, etc.
Prevalence

4-

Recent studies have reported a high prevalence of hypertension

in both urban & rural areas, in India

2ALKALOSIS

-900

-600

-300

+300

K+ Deficit (mEq)

K+ Excess (mEq)

In urban area the prevalence varies from 30 -45 % in

different regions, which is consistent with the findings with
other developing countries in Asia where prevalence is
50% Epidemiological studies report that currently 70% of
hypertension in India is Stage I (140 159 / 90 99 mmHg.)
& rest of are Stage II.

Mechanism
of hypokalemia
Fig. 2 : Relationship between the Serum potassium
concentration
Prevalence of resistant hypertension in India is unknown.
& changes in total body potassium content.

Hypokalemia: High K+ excretion

Reason? (Can be both)
High [K+] CCD

High Flow Rate

ECFV?

Osmoles?
Lytes

Organics

* High NaCl input

* Diuretics loop,
Thiazide, or
Cal types

Not low =
Faster Na+

* Glucose
* Urea
* Mannitol

Low =
Slower Cl -

* Primary high
aldosterone
* AME syndrome
* GRA
* Liddle
* Amphotericin B

Hypokalemia

Fig. 3 : Mechanism of hypokalemia

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Faster Na

Slower Cl-

* Bartter
* Gitelman
* Bicarbonaturia
* Low Cl - delivery

* Liddle
* Amphotericin B

Hypokalemia

Medicine Update 2012 Vol. 22

Faster Na +

Slower Cl-

Na +
Electro
-negative

Electronegative
Cl -

K
Na

* TTKG
* ECFV
* Urine [Na + + Cl -]
if ECFV low

* TTKG
* ECFV
* Urine [Na + + Cl -]
not
Fig. 4 : Hypokalemia
Table 1 : Causes of K+ depletion

50

Extrarenal (Urine K+ < 20mmol/

day)

40
30

Urban

20

Rural

10
0

Prevalence

Awareness

Treatment

Control

Renal (Urine K+> 20mmol/day)

Inadequate intake

Renal tubular acidosis

Copious perspiration

Diabetic ketoacidosis

Gastrointestinal losses

Chloride depletion

Fig. 5 : Status of hypertension prevalence, awareness, treatment &

control in India.

Diarrhoea

Vomiting/gastric suction

Laxative abuse

Diuretics

Villous adenoma

Status of hypertension prevalence, awareness, treatment and

control in India.

Bartters syndrome
Gitelmans syndrome
Mineralocorticoid excess states

(4608 middle aged women, 35 70 years, in 4 urban and 5

rural cites.)

Liddles syndrome
Glucocorticoid excess

What is the relation between Hypertension & Hypokalemia?

Magnesium depletion

Hypertension & hypokalemia are two distinct clinical

syndromes which may or may not be associated. Relation
between these two clinical syndromes can be established as
follows.

Antibiotic therapy

1. Aetiology of hypertension is associated with hypokalemia.

Diuretic conditions.

Endocrine cause

2. Treatment of HTN may lead to hypokalemia

Primary hyperaldostronism

Aetiology of HTN associated with hypokalemia.

Secondary hyperaldostronism

Among all the causes of HTN, the following are related to

hypokalemia.

Cushing Syndrome.

Congenital adrenogenital syndrome

Leukaemia
Interstitial nephritis immune related

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Hypertension and Hypokalemia

Table 2 : Mineralocorticoid Excess States
High aldosterone
Low PRA

Low aldosterone and PRA

High PRA

Primary hyperaldosteronism

Normal cortisol

Glucocorticoid-remediable

Main renal arteries

Aldosteronism (GRA)

Small vessels

Low cortisol

High cortisol
Familial Glucocorticoid resistance

Exogenous Mineralocorticoid Adrenogenital syndrome

Renovascular disease

17-- Hydroxylase deficiency

11--HSD deficiency

11--Hydroxylase deficiency

Congenital
Liquorice

Renin secretory tumour

Carbenoxolone
Liddles syndrome
Algorithm depicting the diagnostic approach to hypokalemia

MR activation mutation.

ileus occurs when smooth muscle function is affected.

More severe hypokalemia my lead to complete paralysis, hypoventilation or rhabdomyolysis

Exclude spurious/transcellular shift

Decreased total body K+

Urine K+ < 25 mEq/d

Urine K+ > 30 mEq/d

Acid-base status

Acid-base status

Normal acid-base

Metabolic acidosis

* Profound
sweating
* Prolonged
decreased intake
* Remote diuretic,
NG suction,
or vomiting

Lower GI loses

Metabolic alkalosis

* Cushing syndrome
* Apparent
Mineralocorticoid excess
* Liddles syndrome
* CAH

4. Polydipsia & Polyuria may result for hypokalemia induced NDI.

Normal acid-base

5. Possible causes of transcellular shift should be sought,

such as use of bronchodilators in COPD. Diuretic &
laxative abuse & recurrent vomiting should be excluded.

Post ATN/post
obstructive diuresis
Osmotic diuresis
Gentle diuretic use
Urine [Cl-]> 20mEq/L [Mg ++]
High-dose penicillin
Polydipsia/DI
Blood pressure

Urine [Cl-] < 20mEq/L

* NG suction
* Vomiting

Hypertensive

Normal/low aldosterone

3. K+ depletion is associated with increased risks of arrhythmias leading to palpitation or Syncope.

Normotensive/
hypotensive

High aldosterone

Aggressive diuretic use

Bartters or
Gitelmans
Syndrome

6. Sign of hypovolemia or hypervolemia, hypotension/ hypertension provides the clue to the aetiology.
7. ECG changes of hypokalemia do not correlate well with
the plasma [K+]. Early changes may include flattening or
inversion of T waves a prominent U wave (more than 1
mm in height) S.T.segment depression and a prolonged
Q u interval. Severe K+ depletion may result in a prolonged PR interval, decreased voltage and widening of
QRS complex.

Metabolic acidosis

Type 1 or 2 RTA
Amphotericin B
DKA
Acetazolamide

* Primary hyperaldosteronism
* Secondary hyperaldosteronism

We approach these patients by check there Urinary K+

excretion & look for TTKG (transtubular potassium gradient)

Algorithm depicting the diagnostic approach to hypokalemia, ATN, acute tubular necrosis; CAH,
congenital adrenal hyperplasia; DI,diabetes insipidus; DKA, diabetic ketoacidosis; GI,
grastrointestinal;NG, nasogastric;RTA, renal tubular acidosis.

TTKG =

Fig. 6 : Algorithm depciting the diagnostic approach to hypokalemia

Renal
Renal parenchymal disease.
Renovascular hypertension
Renin producing tumors.

(Urinary K+/plasma K+)

Urinary osm/plasma osm
Increased loss

Secondary
hyperaldosteronism

24 hrs UK, TTKG

Clinical Presentation

UK > 30mEq/day, TTKG >7

1. Clinical presentation may be related to both of hypertension & hypokalemia. Features of K+ depletion vary
greatly & their severity depends in part on the degree
of hypokalemia. Symptoms seldom occur unless the
plasma [K+] is < 3/mEq/L.
2. Fatigue, myalgia, muscular weakness or cramps of lower extremities are common. Constipation or paralytic

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Renal loss

Check BP

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Algorithm for diagnosis

Secondary hyperaldosteronism

24 hrs free cortisol

Normal

<4 x increase

No Cushings syndrome

Definition:-Increase in the level of aldosterone in response

to activation of renin-angiotensin system.

>4 x increase

Renovascular hypertension: This is hypertension secondary

to Renovascular disease.
It is suspected if:-

Low dose DST to confirm the diagnosis Diagnosis of Cushings

syndrome

Measure ACTH

ACTH increased

ACTH decreased

MRI pituitary

CT Scan of Adrenal

Fig. 7 : Algorithm for diagnosis

Primary Hyperaldosteronism
Definition: - Diastolic hypertension without oedemn,
decreased renin & increased aldosterone secretion
Aetiology
1. Aldosterone producing adrenal adenoam (Conns syndrome) 75 %
2. Adrenal hyperplasia (25%)

Negative family history of HTN

Spontaneous hypokalemia

Sudden onset of exacerbation of HTN.

Difficult to control with antihypertensive therapy.

Pathophysiology: - There is decreased in renal perfusion

in one or both kidneys leading to increased renin release &
subsequent Angiotension II production.
It is two types

Atherosclerotic plaque prox rd of renal artery involved, usually male> 55 years.

Fibromuscular hyperplasia distal rd of renal artery

involved usually in young females.

Cushing Syndrome

Clinical features:

Definition:-Clinical syndrome
Glucocorticoid excess.

Hypertension

Aetiology ACTH dependant

Polyuria polydipsia - nocturia

Fatigue weakness paresthesia

a. ACTH secreting pituitary adenoma (Cushings disease

80 %)

Headache

Severe case Tetany Intermittent paralysis

results

ACTH independant
a. Long term use of exogenous Glucocorticoid

Urea & electrolytes hypokalemia, mild hypernatremia,

hypomagnesaemia

b. Primary adrenocortical Tumor.

High 24 hrs or plasma aldosterone + low random plasma

renin.

Pituitary Transphenoidal resection

CT or MRI (to differentiate adenoma from hyperplasma)

Medical
Spironolactone (aldosterone antagonist or Amiloride.)
ACEI might be added for better control of BP
Surgical
Removal of adenoma

chronic

b. Ectopic ACTH secreting tumor (SCLC)

Investigations:

Treatment:

from

Treatment:
Irridiation only 50 % Effective
Adrenal Adenoma Unilateral adrenalectomy
Carcinoma palliative
Ectopic ACTH
Chemotherapy, Radiation
Ketoeonazole, Metyrapone.
Laboratory Tests for Evaluation of Hypertension
BASIC TEST FOR INITIAL EVALUATION
1. Always included

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Hypertension and Hypokalemia

a. Urine for protein, blood, and glucose

b. Microscopic urinalysis

Treatment of Hypokalemia

c. Hematocrit

d. Serum potassium

e. Serum creatinine and /or blood urea nitrogen.

f. Fasting glucose

g. Total cholesterol

iii. Potassium sparing diuretics may be prescribed

carefully to avoid hyperkalemia

Therapeutic goalsa. Prevent life threating complication (Arrhythmias, Respiratory failure.)

b. Correct K+ deficit.

h. Electrocardiogram

c. Minimize ongoing loss through treatment of underlying

cause.

2. Usually included, depending on cost and other factors

Assessment of K+ deficit-

a. Thyroid-stimulating hormone

b. White blood cell count

If the hypokalemia is due to potassium depletion (where

transcellular shift e.g. alkalosis is excluded)-

c. HDL and LDL cholesterol and triglycerides

d. Serum calcium and phosphate

e. Chest x-ray; limited echocardiogram.

Every 1mmEq/ L [K+] depletion = 10 % Reduction of total

body K+ store.
[Total body K+ content = 50mEq/ KG]
For a 60 kg person, total body K+ store = 60 x 50= 3000 mEq.

SPECIAL STUDIES FOR SECONDARY HYPERTENSION

Therefore,

1. Renovascular disease: angiotension-converting enzyme

inhibitor radionuclide renal scan, renal duplex. Doppler
flow studies and MRI angiography.
2. Pheochromocytoma: 24-h urine assay for creatinine,
metanephrines, and catecholamines.
3. Cushings syndrome: overnight dexamethasone suppression test or 24-h urine cortisol and creatinine.
4. Primary aldosteronism: plasma aldosterone: renin activity ratio.
Management

1 mEq/ L [K+] depletion = 3000 x 10% = 300 mEq. = Total

K+ deficit.
Oral therapy:
i. It is generally safer to correct hypokalemia via oral
route. KCl is usually preparation of choice for hypokalemia + Metabolic alkalosis.
ii. Potassium bicarbonate & citrate tend to alkalize the
blood, may be useful in correcting hypokalemia associated with chronic diarrhea or RTA.
iii. Potassium phosphate may be preferred for DKA.

Treatment of hypertension & hypokalemia includes the

following-

IV therapy: Imminently life threating hypokalemia (unable

to take KCl orally.)

1. To identify the cause & treat the cause.

Concentration of K+ administration

2. Treatment of hypertension & prevention of hypokalemia.

40 mEq/ L in peripheral vein

3. Treatment of hypokalemia

K+ solutions are hyperosmotic, therefore should be diluted

with NS always (Dextrose should be avoided to prevent
transcellular shift of K +.

Treatment of hypertension & prevention of hypokalemia

a. Life style modification.

Rate of infusion - 20mEq/ hour.

b. Diet & exercises.

Advised to consume fruits & fruit juice & K+ containing

salt preparation

c. Antihypertensive medication

i.

Avoid use of diuretics.

ii. ACEI/ARB preferred.

100 mEq/ L in central vein.

Hypomagnesaemia should be sought in all hypokalemic

patients and corrected to allow effective K+ repletion.
Conclusion
Hypertension & hypokalemia are distinct clinical Syndromes
which can be correlated clinically & biochemically. Both the
conditions are widely prevalent among different groups of

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patients. Prevention and treatment of these clinical states

depends on proper history taking & examination, clinical
suspects, laboratory investigations & its adequate proper
management. Though these two conditions are mild in most
of the instances these can be life threatening & should be
managed aggressively & adequately in ICU setup.
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Rose BD, POST tw. Potassium homeostasis In: Clinical physiology of acid-base and electrolytes disorders 5th edition. NewYork.
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Clin North America 2055; 23:723-747
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Grover P. Hypokalemia. Crit care Rescue 1999; 1 :239-251

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Kamel S. Kamel, Mn S. Oh & Mitchell L. Halperin Treatment of

hypokalemia & hyperkalemia, Therapy in Nephrology 7 Hypertension A companion to Brenner and Rectors

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Anbry Morrision & Anitha Vijayan Hypertension 102 The Washington Manual of Medical Therapeutics. 32ND Edn 2007.

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Rajeev Gupta: Resistant hypertension: A clinical perspective 5160. Medicine update, API, Volume 21, 2011

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