Serum electrolytes in hypertension in Nigerians

CLINICA CHIMICA ACTA

105

SERUM ELECTROLYTES

IN HYPERTENSION

IN NIGERIANS

L. A. SALAKO

Department

of Medicine,

University

College Hospital,

Ibadan (Nigeria)

(Received March II, 197')

SUMMARY

Untreated Nigerians with essential hypertension were found to present frequently with low serum potassium unassociated with acidosis or alkalosis. Possible relationships between this fmding and the high incidence of renal failure amongst hypertensive Nigerians are discussed.

INTRODUCTION

Although early reports of surveys of arterial hypertension in Africans suggested that the disease was uncommon in the indigenous populationlla, recent investigations have shown that hypertension is, in fact, at least as common in the African as it is in Causa.sians3p4. An important feature of these later studies is that the clinical picture of hypertensive disease in many parts of Africa differs in several important respects from the clinical picture of the disease as described from other parts of the world. Thus amongst the Bantu population of South Africa, Schrire3 found hypertension to be more common and to present more severely at an earlier age than in the white community. Associated and possibly causal renal lesions were also found to be more common. In Nigeria, Abrahams and col14 observed that heart failure was a common mode of presentation while coronary artery disease was rarely seen, and Akinkugbe5 showed that hypertensive retinopathy was uncommon. After observing hypokalaemia frequently in hypertensive patients attending the outpatients department of the University College Hospital, Ibadan, Nigeria, it was decided to investigate prospectively the serum electrolytes and other biochemical parameters in an unselected series of patients with uncomplicated essential hypertension. MATERIALS

AND METHODS

The subjects were chosen from amongst new patients attending the hypertension clinic of the University College Hospital Ibadan. All patients were assessed clinically, radiologically and biochemically to determine the severity of the hypertension and to identify any causative factors. Patients included in the study were those found to have no identifiable cause for the hypertension and who had not been on any known Clin. Chim.Acta, 34 (1971) 105-111

106

SALAKO

previous antihypertensive or diuretic therapy. Of the 56 patients who satisfied these criteria 25 (44.6%) had incipient or overt heart failure and were further excluded. Of the remaining 31 who formed the material of this study, none had any symptoms which could be directly attributed to hypertension. Hypertension had been discovered as an incidental finding on clinical examination, subjects having usually come to hospital because of such symptoms as malaise, insomnia, headache and a general feeling of unwell. Of the 31 patients 19 were females and 12 males. Their diastolic pressure ranged between IOO and 150 mm Hg. All had electrocardiographic evidence of left ventricular hypertrophy with or without strain. About + of the patients had undoubted radiological evidence of left ventricular enlargement. Fundal examination in the 31 patients showed that 6 had grade 2, 12 grade I and 13 grade o retinopathy, using the classification of Keith et al. 6. The ages ranged from 24 to 69 years. Serum and urinary potassium and sodium were estimated by standard flame photometry, chloride by the method of Schales and Schales’, calcium by the chelation method of Trinders, bicarbonate by means of the Natelson microgasometer+‘, urea by urease Nesslerizations, creatinine by a modified Folin-Wu tungstic acid methods and inorganic phosphate by the method of King and Woottonlo. Osmolality was determined by the freezing point depression method using a Fiske Osmometer. Because of the possibility of an association between hypokalaemia on one hand and low serum phosphate from increased urinary phosphate excretion on the other, plasma phosphate and tubular reabsorption of phosphate were determined in 13 patients who at 3 consecutive weekly visits to the outpatients clinic had serum potassium of less than 3.5 mequiv/l. The test was performed in outpatients, with the subjects in the fasting state, and having been previously instructed to keep to a steady normal diet for 3 days preceding the test. Venous blood was collected at IO a.m. and urine from 9 a.m. to II a.m. The tubular reabsorption of phosphate, expressed as mg of phosphorus absorbed per IOO ml of glomerular filtrate (% TRP x P) was calculated using the formulall, %TRP

x P (mg P/IOO ml glomerular

filtrate

=

[I-=J

x rp

where : up ccr Pp per

= Urine phosphate (mg/roo ml) = Urine creatinine (mg/roo ml) = Plasma phosphate (mg/roo ml) == Plasma creatinine (mg/roo ml)

The phosphate excretion index (PEI) was also calculated in these 13 subjects using the formula of Nordin and FraserIs. Because the subjects were generally asymptomatic it was difficult to convince them to come into hospital for a 24-h creatinine clearance test. An attempt was therefore made to collect 24-h urine on outpatient basis. Patients were asked to collect 24-h urine in their homes and blood was taken in hospital towards the end of the collection period. To determine whether reproducible results could be obtained with this method, the clearance was estimated in each of 5 patients on 3 consecutive Mondays. The results were so widely different in each individual that it was concluded that the outpatient collection of urine would not give satisfactory values for the creatinine C&z. Chim.

Acta,

34 (1971)

105-111

HYPERTENSION

IN NIGERIANS

107

clearance. 14 patients however agreed to be admitted for this purpose, hence only the creatinine clearance of these patients was included in this report. RESULTS

Fig. I shows the distribution of serum electrolytes in the group of 31 patients when first seen in hospital. The most striking feature is that for most of the patients

150

lb0

130

120

.- -__

. . . .. l 7. l -‘-’ .‘.‘. . . . .:.: . . .-.

- .----

5.5

SD

. . L.5

_- .-_.--_

E

120-

36-

llo---~--

32-

.

\ > .2 &

LO-

. . . . . . .

loo-

. . . .e

: .* a ..

l

. 26-

. . .

. . .

. .

. 24-

.

3.0 .

.

. . . . .

.

.

. .

.

*. 100

. .

.. . . .*.. go-

.

_--_e-_

. .t . . ----.-_

. .. 35

'lo

.

. .

L.0

.

130-

.

. .

.

.

. .

.

BO-

20_--_.-.-_

70-

16-

. . .

. 90

2.5 .

.

.

. 60

2.0 Na’

K’

60

I2

Cl‘

HCOj

Fig. I. Distribution of serum sodium, potassium, chloride and bicarbonate with uncomplicated essential hypertension.

in 31 Nigerian patients

the values of serum potassium, and to a less extent sodium, were below the normal range (indicated by broken lines) previously determined for this communityl3. For the 31 patients, the ranges and means (& S.D.) of the serum electrolytes were: sodium, rrg-140,131 & 6; potassium, 2.2-4.9,3.4 f 0.66; chloride, 85-110,97 & 6.15 and bicarbonate, 16-31, 24 & 3.5. By contrast, the serum sodium and potassium determined in 24 volunteer medical students (Fig. 2) agreed more closely with the previously determined normal range, with a mean of Na, 138 f 3.1; and K, 4.7 & 0.48. Blood wea The mean blood urea in the group of 31 patients was 30 f C&z. Chim. Acta,

8.6 mg% with a 34

(1971)

105-111

108

SALAKO

155

150

7.0

_----

6.5

IL5

6.0

.

. 7 .?

.

.

it w 1LO E

.

. . . .. . . . . . . . . - -.....--

135

5.5

__--.. . . . . .

5.0

.

. .

. .

130

.

c.5

l .

”

.-_i_

.

0 . . . .

. 125

L.0

. .

120

3.5,

Na+

Fig. 2. Distribution

K+ of serum sodium and potassium

in 24 volunteer

“normal”

medical students.

range of 16 to 46. Six patients had an initial blood urea value which was higher than the upper normal value (36 mg%) for the population. Three weeks later, the blood urea in all 6 had fallen to within the normal range even before any treatment was instituted. Plasma creatinine Plasma creatinine in all patients fell below the reported upper limit of normal of z mg per IOO m113.The values were in the range of 0.7 to 1.8 mg/Ioo ml with a mean value of 1.2 f 0.32 (S.D.). Creatinine clearance As shown in Table I, the creatinine clearance in 14 patients averaged 83.8 f 10.9 (SD.) and was significantly lower than the mean creatinine clearance (111.0 f 11.5 (S.D.)) for IO control subjects. These were male patients in hospital for investigation of symptoms of a functional nature. None of these control subjects were found to have a dysfunction of the renal, cardiovascular or gastrointestinal system. Table I also shows that of the 14 hypertensive patients only one had a serum potassium level of Clin. Chinz.Ada, 34 (1971) 105-111

HYPERTENSION

TABLE

IN

109

NIGERIANS

I

SERUM

POTASSIUM,

TIENTS

AND

NO.

IO

PLASMA

CREATININE

AND

CREATININE

CLEARANCE

IN

14

HYPERTENSIVE

Hy@rtensives

Controls Plasma creatinine (mg/Ioo ml)

Creatinine clearance

Serum potassium

Plasma

(mllmin)

(mequiu

(mg/Ioo

2.6

0.8

70.4

3.5

0.6

124.6

2.6

I.5 I.5

74.5 81.0

4.0 3.5

1.2 0.8

99.4 126.8 114.2

Serum potassizlm

(mequivll)

3.0

Creatinine

creatinine

11)

clearance ml)

(mljmin)

2.6

I.5

92.4

4.0

0.9

5

3.0

0.7

100.5

3.6

0.5

96.8

6

3.1

1.0

95.4

3.2

0.8

121.4 106.8

2.2

0.7

80.4

4.1

I.4

i

2.9

0.7

74.2

3.8

1.3

104.9

9

3.8

I.0

73.4

3.9

0.9

119.4

1.1

95.2

3.8

1.5

95.2

;::4

IO II

2.8 2.6

12

2.5

0.7 1.0

2.8

1.0

77.4 83.8

2.8

zm

S.D.

0.37

f

PA-

CONTROLS

f

over 3.5 mequiv/l whereas in 9 of the mequiv/l and above.

I.0

3.7

IO.9

f

IO

0.29

+

111.0

0.34

?c 11.5

control subjects serum potassium was 3.5

Urine/plasma osmolality ratio Osmolality was measured in random samples of urine and blood taken simultaneously before mid-day in all 31 patients. The results show that the plasma osmolality ranged from 281 to 305 and was always less than the osmolality of the urine sample taken at about the same time, the urine/plasma osmolality ratio ranging from 1.4 to 3.8.

TABLE

II

TUBULAR

REABSORPTION

PHOSPHATE,

Case No.

POTASSIUM

OF PHOSPHATE AND

AND PHOSPHATE

CREATININE

IN

13

EXCRETION

HYPERTENSIVE

INDEX

IN RELATION

TO SERUM

PATIENTS

Plasma creatinine (mg/Ioo ml)

Serum potassium (mequivll)

Plasma Phosphorus (mglzoo ml)

y’ TRP x P (mglloo ml)

PEI

3.8 2.6 2.4 4.0 3.1 3.6

-0.08 -0.05

I

1.0

2.8

2

I.0

2.2

3 4 2

I.5 0.8

0.9 0.9

3.0 2.6 2.5 3.2

4.1 2.7 2.6 4.2 3.4 3.8

1.8

2.6 2.7

2.2

2.2

-0.03

3.7

3.5

-0.07

s7

0.7

II 12

I3

1.1

3.0

3.1

3.0

-0.08

3.0 3.0 3.2

5.8 4.2 3.8 3.1

5.6 3.8 3.5 3.0

-0.08 -0.08 -0.07

2.2

yO TRP

x P

PEI

Phosphase

=

-0.10 -0.04

0.7 I.5 1.5 0.7

9 IO

0 -0.12

=

Tubular

reabsorption

Excretion

of

PO,

per

IOO ml

of glomerular

-0.22

filtrate.

Index.

Clin. Chim. Acta, 34 (1971)

rag-III

110

SALAKO

Tubular reabsorption of phosphate and phosphate excretion index The values obtained for these estimations are shown in Table II. Of the 13 hypokalaemic patients studied, none had hypophosphataemia (normal, 2-4 rng%l”). None of the patients had a reduced %TRP raised PEI (> +o.og).

x P (below 2.1 mg/roo ml) and none had

DISCUSSION The result of this survey shows that a substantial proportion of untreated hypertensive Nigerians presented with a low serum potassium without acidosis or alkalosis. Even amongst the patients with serum potassium levels of below 2.5 mequiv/l no symptoms could be directly attributed to hypokalaemia. Although many of the patients presented with malaise and “weakness”, these were usually vague expressions of a state of ill health rather than muscular weakness. The associated low serum sodium may be of importance in this respect since it is known that the effect of low serum potassium on muscular power may be antagonised by a decrease in sodium ionsl*. In addition, the usual changes in ECG associated with hypokalaemia were not observed in any of the hypokalaemic patients. The cause of the low serum potassium and sodium levels is at present not certain, neither is it known whether the low serum levels were associated with true body deficit of the ions. Further studies still need to be done in this regard. It is however worthy of note that none of the patients had any history of acute or chronic gastrointestinal fluid loss, and potassium intake in Nigerians is usually adequate. Recently MacFarlane and associates r5, from a study of blood donors at Ibadan, suggested that serum potassium and sodium levels in “normal” Nigerians are lower than in Europeans and Americans. As their values for normals differed from those of an earlier report by Edozienra and for 24 normal medical students in this survey, the question of what is the normal electrolyte value in Nigerians is still open to doubt. Nevertheless, it is of interest that 18 out of 31 patients had serum potassium levels lower than 3.5 mequiv/l and 14 out of 31 had sodium levels lower than 130 mequiv/l, whereas none of 24 normal medical students examined during the same period had potassium level below 3.5 mequiv/l or sodium level below 130 mequiv/l. Since renal failure occurs more commonly in the course of essential hypertension in this community than in Europeans16, it is possible that the low potassium level observed in many of the patients is related to renal dysfunction either as a cause of it or as an early manifestation. The normal blood urea and plasma creatinine and the absence of hyposthenuria in the patients suggest that there was no severe impairment of renal function in the group. The creatinine clearance in 12 patients was significantly lower than in IO control subjects indicating a reduction in glomerular filtration rate. This effect could however be due to increased resistance in the afferent and and efferent arterioles (in parallel with a general increased peripheral vascular resistance) rather than a damage to the glomerular tuft. Association of hypokalaemia with hypophosphataemia and hyperphosphaturia has frequently been reportedIT. Such an association may be due to a factor, like hyperadrenocorticism, which affects the metabolism of both ionslS-zO or, as recently pointed out by Anderson et aLa and Condon and Nassimz2, hypokalaemia can by itClin. Chim. Acta, 34 (1971) 105-111

HYPERTENSION

III

IN NIGERIANS

self lead to low plasma

phosphate

and increased

urinary

phosphate

excretion.

It is

therefore of interest that none of the patients with persistent hypokalaemia in this series had a low serum phosphate level, and none had evidence of increased urinary excretion of phosphate. It can therefore be concluded that factors like hyperadrenocorticism, which could cause both hypokalaemia and hypophosphataemia, are not of importance in these patients, neither has the hypokalaemia itself affected the kidney to the extent

of causing a disturbance

of phosphate

excretion.

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10 I1 12 I3 I4 I5

16 I7

18 =9 20 21 22

P. DONNISON, Lancet, i (Igzg) 6. W. VINT, E. Afr. Med. J., 13 (1937) 332. SCHRIRE, Amer. Heart J., 56 (1958) 742. G. ABRAHAM& C. A. ALELE AND B. G. BARNARD, w. Afr. Med. J., g (1960) 45. 0. 0. AKINKUGBE, Amer. 1. Med., 45 (1968) 401. N. M. KEITH, H. P. WAGONER AND'~.‘%. BARKER, Amer.J.Med. Sci., 197 (1939) 332. 0. SCHALES AND S. S. SCHALES. I. Biol. Chem., 140 (1941) 879. P. TRINDER, Analyst, 85 (1960) SSg. H. VARLEY, Practical Clinical Biochemistry, 3rd ed., W. Heinemann Medical Books, London, 1962. E. J. KING AND 1. D. P. WOOTON, Micromethods in Clinical Biochemistry, 4th ed., Churchill, London, 1964. W. C. THOMAS, Jr., T. B. CONNOR AND H. G. MORGAN, J. Lab. Clin. Med., 52 (1958) II. R. E. C. NORDIN AND R. FRASER, Lancet, i (1969) 947. J. C. EDOZIEN, u7. Afr. Med. J., 7 (1958) 121. D. A. K. BLACK, in G. A. SMART (Ed.), Metabolic Diseases in Clinical Medicine, Churchill, London, 1958, p. 29. H. MCFARLANE, 0. 0. AKINKUGBE, A. C. ADEJUWON, I. A. 0. OFOROFUO, 0. A. ONAYEMI, 0. LONGE, 0. A. OJO AND S. REDDY, Clin. Chim. Acta, 29 (1970) 273. 0. 0. AKINKUGBE, E. Afr. Med. J., 46 (1969) 313. Editorial, Lancet, i (1970) 820. K. D. BAGSHAWE, T. R. CURTIS AND E. S. GARNETT, Lancet, i(1965) - _, 18. F. CAMANXI, O.LO~ANA, F.MASSARA AND G.M.MOLINATTI,.A&z Endocrinol., 56(1967) 85. S. L. STEELMAN AND R. HIRSCHMANN, in A. B. EISENSTEIN (Ed.), The Adrenal Cortex, Churchill, London, 1967, p. 345. D. C. AXDERSON, T. J. PETERS AND W. K. STEWART, Brit. Med. J., iv (1969) 402 J. R. CONDON AND R. NASSIM, Brit. Med. J., i (1970) 110. Clin. Chim. Acta, 34 (1971) 105-111