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HYPERTENSION AND HYPOKALEMIA

Sekhar Chakraborty, Siliguri

INTRODUCTIONHypertension 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 influencemovement of [K+] into the cells.

K+ excretion is regulated at the distal nephron.

K+excretionisrelatedto(Urineflowrate)

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

3 : 5

Fig. 1 : Intracellular & extracellular content of potassium

4000 3000 353500 2000 70 mEq 1000 0

Intracellular Potassium Extracellular Potassium

Tota

l Bod

y K

(mEq

)

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Hypertension and Hypokalemia

Fig. 2 : Relationship between the Serum potassium concentration & changes in total body potassium content.

10 8 (70 kg Adult) Serum K+ (mEq/ L) 6 -

ACIDOSIS 4 - 2 - ALKALOSIS -900 -600 -300 +300 0 K+ Deficit (mEq) K+ Excess (mEq) Mechanism of hypokalemia

Hypokalemia: High K+ excretion Reason? (Can be both) High Flow Rate High [K+] CCD Osmoles? ECFV? Lytes Organics Not low = Low = Faster Na+ Slower Cl - * High NaCl input * Glucose * Primary high * Bartter * Diuretics loop, * Urea aldosterone * Gitelman Thiazide, or * Mannitol * AME syndrome * Bicarbonaturia Cal types * GRA * Low Cl - delivery * Liddle * Amphotericin B

Hypokalemia Faster Na + Slower Cl- Na + Electro Electro- -negative negative Cl - K * TTKG * TTKG Na * ECFV * ECFV * Urine [Na + + Cl -] * Urine [Na + + Cl -]

if ECFV low not

Fig. 3 : Mechanism of 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-

UptakeofK+intocellsbyalteringactivityofNaK-ATPs pump in the cell membrane.

Renalexcretionmainlycontrolledbyaldosterone.

Extrarenallosse.g.gastrointestinal.

DefINITION Of HyPOKalemIaHypokalemia has been defined as Serum [K+] is < 3.5 mEq/ L. Severe hypokalemia where

Serum [K +]= 20mmol/day)

Inadequate intake

Copious perspiration

Gastrointestinal losses

Diarrhoea

Laxative abuse

Renal tubular acidosis

Diabetic ketoacidosis

Chloride depletion

Vomiting/gastric suction

Diuretics

Villous adenoma Bartters syndrome

Gitelmans syndrome

Mineralocorticoid excess states

Liddles syndrome

Glucocorticoid excess

Magnesium depletion

Antibiotic therapy

Leukaemia

Interstitial nephritis immune re-lated

Diuretic conditions.

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

0

10

20

30

40

50

Prevalence Awareness Treatment Control

UrbanRural

Mechanism of hypokalemia Hypokalemia: High K+ excretion Reason? (Can be both) High Flow Rate High [K+] CCD Osmoles? ECFV? Lytes Organics Not low = Low = Faster Na+ Slower Cl - * High NaCl input * Glucose * Primary high * Bartter * Diuretics loop, * Urea aldosterone * Gitelman Thiazide, or * Mannitol * AME syndrome * Bicarbonaturia Cal types * GRA * Low Cl - delivery * Liddle * Amphotericin B

Hypokalemia Faster Na + Slower Cl- Na + Electro Electro- -negative negative Cl - K * TTKG * TTKG Na * ECFV * ECFV * Urine [Na + + Cl -] * Urine [Na + + Cl -]

if ECFV low not

Fig. 4 : Hypokalemia

Status of hypertension prevalence, awareness, treatment and control in India.

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

What is the relation between Hypertension & Hypokalemia?

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.

1. Aetiology of hypertension is associated with hypoka-lemia.

2. Treatment of HTN may lead to hypokalemia

Aetiology of HTN associated with hypokalemia.

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

Endocrine cause

Primaryhyperaldostronism

Secondaryhyperaldostronism

CushingSyndrome.

Congenitaladrenogenitalsyndrome

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Table 2 : mineralocorticoid excess statesHigh aldosterone low aldosterone and PRa

low PRa High PRa Normal cortisol low cortisol High cortisol

Primary hyperaldosteronism

Glucocorticoid-remediable

Aldosteronism(GRA)

Renovascular disease

Main renal arteries

Small vessels

Renin secretory tumour

Exogenous Mineralocorticoid

11--HSDdeficiency

Congenital

Liquorice

Carbenoxolone

Liddles syndrome

MR activation mutation.

Adrenogenital syndrome

17--Hydroxylasedeficiency

11--Hydroxylasedeficiency

Familial Glucocorticoid resistance

Fig. 6 : Algorithm depciting the diagnostic approach to hypokale-mia

RenalRenal parenchymal disease.

Renovascular hypertension

Renin producing tumors.} Secondary hyperaldosteronism

ClINICal PReseNTaTION1. Clinical presentation may be related to both of hyper-

tension & 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 low-er extremities are common. Constipation or paralytic

Algorithm depicting the diagnostic approach to hypokalemia

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 Metabolic alkalosis Normal acid-base * Profound Lower GI loses Post ATN/post sweating obstructive diuresis * Prolonged Osmotic diuresis decreased intake Gentle diuretic use * Remote diuretic, Urine [Cl-] < 20mEq/L Urine [Cl-]> 20mEq/L [Mg ++] NG suction, High-dose penicillin or vomiting Polydipsia/DI * NG suction Blood pressure * Vomiting Hypertensive Normotensive/ Metabolic acidosis hypotensive Normal/low aldosterone High aldosterone Aggressive diuretic use Type 1 or 2 RTA Bartters or Amphotericin B Gitelmans DKA Syndrome Acetazolamide * Cushing syndrome * Apparent Mineralocorticoid excess * Primary hyperaldosteronism * Liddles syndrome * Secondary hyperaldosteronism * CAH 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.

ileus occurs when smooth muscle function is affected. More severe hypokalemia my lead to complete paraly-sis, hypoventilation or rhabdomyolysis

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

4. Polydipsia & Polyuria may result for hypokalemia in-duced NDI.

5. Possible causes of transcellular shift should be sought, such as use of bronchodilators in COPD. Diuretic & laxative abuse & recurrent vomiting should be excluded.

6. Sign of hypovolemia or hypervolemia, hypotension/ hy-pertension provides the clue to the aetiology.

7. ECG changes of hypokalemia do not correlate well with the plasma [K+].Earlychangesmayincludeflatteningorinversion of T waves a prominent U wave (more than 1 mminheight)S.T.segmentdepressionandaprolongedQ u interval. Severe K+ depletion may result in a pro-longed PR interval, decreased voltage and widening of QRS complex.

We approach these patients by check there Urinary K+ excretion&lookforTTKG(transtubularpotassiumgradient)

TTKG = (Urinary K+/plasma K+)

Urinary osm/plasma osm

Increased loss

24 hrs UK, TTKG

UK > 30meq/day, TTKG >7

Renal loss

Check BP

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PRImaRy HyPeRalDOsTeRONIsmDefinition: - Diastolic hypertension without oedemn, decreased renin & increased aldosterone secretion

Aetiology

1. Aldosterone producing adrenal adenoam (Conns syn-drome)75%

2. Adrenalhyperplasia(25%)

ClINICal feaTURes:Hypertension Polyuria polydipsia - nocturia

Fatigueweaknessparesthesia

Headache

SeverecaseTetanyIntermittentparalysis

Investigations: Urea & electrolytes hypokalemia, mild hypernatremia,

hypomagnesaemia

High24hrsorplasmaaldosterone+lowrandomplasmarenin.

CTorMRI (todifferentiate adenoma fromhyperplas-ma)

Treatment:Medical

Spironolactone(aldosteroneantagonistorAmiloride.)

ACEI might be added for better control of BP

Surgical

Removal of adenoma

seCONDaRy HyPeRalDOsTeRONIsmDefinition:-Increase in the level of aldosterone in response to activation of renin-angiotensin system.

Renovascular hypertension: This is hypertension secondary to Renovascular disease.

It is suspected if:-

NegativefamilyhistoryofHTN

Spontaneoushypokalemia

SuddenonsetofexacerbationofHTN.

Difficulttocontrolwithantihypertensivetherapy.

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

Atheroscleroticplaqueprox rdof renal artery in-volved, usually male> 55 years.

Fibromuscularhyperplasiadistalrdofrenalarteryinvolved usually in young females.

CUsHING syNDROmeDefinition:-Clinical syndrome results from chronic Glucocorticoid excess.

Aetiology ACTH dependant

a. ACTH secreting pituitary adenoma (Cushings disease 80%)

b. EctopicACTHsecretingtumor(SCLC)

ACTH independant

a. Long term use of exogenous Glucocorticoid

b. Primary adrenocortical Tumor.

TReaTmeNT:Pituitary Transphenoidal resection

Irridiation only 50 % Effective

adrenal Adenoma Unilateral adrenalectomy

Carcinoma palliative

ectopic aCTH

Chemotherapy, Radiation

Ketoeonazole, Metyrapone.

laBORaTORy TesTs fOR evalUaTION Of Hy-PeRTeNsIONBasIC TesT fOR INITIal evalUaTION1. Always included

Algorithm for diagnosis 24 hrs free cortisol Normal 4 x increase No Cushings syndrome 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

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a. Urine for protein, blood, and glucose

b. Microscopic urinalysis

c. Hematocrit

d. Serum potassium

e. Serum creatinine and /or blood urea nitrogen.

f. Fasting glucose

g. Total cholesterol

h. Electrocardiogram

2. Usually included, depending on cost and other factors

a. Thyroid-stimulating hormone

b. White blood cell count

c. HDL and LDL cholesterol and triglycerides

d. Serum calcium and phosphate

e. Chest x-ray; limited echocardiogram.

sPeCIal sTUDIes fOR seCONDaRy HyPeRTeN-sION1. Renovascular disease: angiotension-converting enzyme

inhibitor radionuclide renal scan, renal duplex. Doppler flowstudiesandMRIangiography.

2. Pheochromocytoma: 24-h urine assay for creatinine, metanephrines, and catecholamines.

3. Cushings syndrome: overnight dexamethasone sup-pression test or 24-h urine cortisol and creatinine.

4. Primary aldosteronism: plasma aldosterone: renin activ-ity ratio.

maNaGemeNTTreatment of hypertension & hypokalemia includes the following-1. To identify the cause & treat the cause.

2. Treatment of hypertension & prevention of hypoka-lemia.

3. Treatment of hypokalemia

Treatment of hypertension & prevention of hypokalemiaa. Lifestylemodification.

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.

iii. Potassium sparing diuretics may be prescribed carefully to avoid hyperkalemia

Treatment of HypokalemiaTherapeutic goals-

a. Prevent life threating complication (Arrhythmias, Res-piratoryfailure.)

b. CorrectK+deficit.

c. Minimize ongoing loss through treatment of underlying cause.

Assessment of K+ deficit-

If the hypokalemia is due to potassium depletion (where transcellularshifte.g.alkalosisisexcluded)-

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.

Therefore,

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 hypoka-lemia + Metabolic alkalosis.

ii. Potassium bicarbonate & citrate tend to alkalize the blood, may be useful in correcting hypokalemia associ-ated with chronic diarrhea or RTA.

iii. Potassium phosphate may be preferred for DKA.

Iv therapy: Imminently life threating hypokalemia (unable totakeKClorally.)

Concentration of K+ administration

40mEq/Linperipheralvein

100mEq/Lincentralvein.

K+ solutions are hyperosmotic, therefore should be diluted with NS always (Dextrose should be avoided to prevent transcellular shift of K +.

Rateofinfusion-20mEq/hour.

Hypomagnesaemia should be sought in all hypokalemic patients and corrected to allow effective K+ repletion.

CONClUsIONHypertension & 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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logy of acid-base and electrolytes disorders 5th edition. NewYork.Mc Graw- Hill, 2001: 372 402

2. Schaefer TJ, Wolford RW. Disorders of potassium. Emerg Med Clin North America 2055; 23:723-747

3. Grover P. Hypokalemia. Crit care Rescue 1999; 1 :239-2514. Kamel S. Kamel, Mn S. Oh & Mitchell L. Halperin Treatment of

hypokalemia & hyperkalemia, Therapy in Nephrology 7 Hyper-tension A companion to Brenner and Rectors

5. The kidney: 35: 349-364. 2nd edited by H.R.Brady & C.S.WILCOX edn.

6. Richard L. Tannen and Kenneth R. Hallows Hypo Hyperkalemia 2.3: 269 286. Oxford Textbook of Clinical Nephrology volume 1. 3RD Edn 2005.

7. Anbry Morrision & Anitha Vijayan Hypertension 102 The Was-hington Manual of Medical Therapeutics. 32ND Edn 2007.

8. Rajeev Gupta: Resistant hypertension: A clinical perspective 51-60. Medicine update, API, Volume 21, 2011

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10. Kamlanathat Sambandham and Anitha Vijayan Fluid and Electro-lyte Management. Potassium 69-76. The Washington Manual of Medical Therapeutics 32 nd Edn 2007.

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