Severe hypercapnia associated with a non-respiratory alkalosis

Br.

J. Dis.

Chest

(1978)

72, 62

SEVERE HYPERCAPNIA ASSOCIATED WITH NON-RESPIRATORY ALKALOSIS

Department

of Medicine,

Guy’s Hospital,

A

London

Summary

A case of hypoventilation in response to a non-respiratory alkalosis is presented. It is postulated that the degree of hypoventilation encountered was a normal response and that a fall in intracellular hydrogen ion concentration was responsible for the hypoventilation. This explains why the alkalosis associated with potassium deficiency is not associated with hypoventilation since the intracellular hydrogen ion concentration then remains constant. The renal response in this condition is responsible for maintaining the alkalosis and seems to be aimed at sodium conservation and hence plasma volume control rather than defence of acid-base balance.

Compensatory hypoventilation in response to a non-respiratory alkalosis (metabolic alkalosis) is uncommon. In the case reported here the Pacoz rose to 10.1 kPa (76 mmHg). In view of the unusual degree of hypoventilation this case of a patient with pyloric stenosis associated with a severe non-respiratory alkalosis is presented. Case Report A 53-year-old man was admitted to hospital having been found in a confused state. On examination he was thin, dehydrated and conscious but unable to give a history. Investigations showed: haemoglobin 12.0 g/100 ml, Naf 130 mmol/litre, K + 3.6 mmol/litre, HC03> 40 mmol/litre, urea 51 mmol/litre (300 mg/lOO ml), and a normal chest radiograph. He was partially rehydrated with normal saline, then became very aggressive and discharged himself from hospital. He was readmitted one month later in an almost identical state, on this occasion two additional factors were noted: firstly he had a right paramedian scar on his abdomen and secondly his respiratory rate was lO/min and appeared shallow. Investigations showed: haemoglobin 12g/ 100 ml, Na* 121 mmol/litre, K+ 2.2 mmol/litre, HC03> 40 mmol/litre and urea 56 mmol/litre (340 mg/lOO ml). Blood gases were as follows: Paoz 8.5 kPa (63 mmHg), Pcco2 10.1 kPa (76 mmHg), Hf 29 mmol/litre (pH 7.56) and HC03calculated 56 mmol/litre. A succussion splash was noted; a nasogastric tube was passed and 500 ml of liquid aspirated from the stomach. Treatment consisted of intravenous normal saline and potassium supplements only for the first few days. He required to be restrained and sedated over the first week. The electrolytes, blood gases and urea returned to normal levels over the next two weeks. A barium meal revealed a complete obstruction at the pylorus. At operation a huge stomach was found with a completely obstructed pylorus. A partial gastrectomy was carried out and histology did not show any evidence of malignancy. He made an uneventful recovery and postoperatively his FEVl was 2.9 litres (predicted 2.7), VC 3.5 litres (predicted 3.5). He had been a smoker all his adult life but did not give any history of chronic cough, dyspnoea or wheezing.

Hypercapnia with Non-respiratory

Alkalosis

63

DISCUSSION Hypoventilation in response to a non-respiratory alkalosis can be viewed either as a normal compensatory response of the respiratory system to an alkalosis or as an abnormal response due to what might be a decreased carbon dioxide responsiveness of the respiratory centre. The chemical control of respiration is mediated via the peripheral and central chemoreceptors. The peripheral chemoreceptors in the aortic and carotid bodies are sensitive to the Paoa and in man significant increase in respiratory drive does not occur until the Paos falls below 60 mmHg (8 kPa) (C omroe 1964). There is evidence that a sudden increase in Paces will potentiate hypoxic drive (Biscoe et al. 1967) but this potentiation has been shown to be absent when Paces has been raised for more than 48 hours (Falchuk et al. 1966). The Paos in this case did not fall below 60 mmHg (8 kl’a). There is evidence to suggest that in some patients it is the hypoxic drive that is responsible for respiratory drive since some patients with this condition given added inspired oxygen hypoventilate even more with a further rise in Pacos (Tuller & Mehdi 1971; Oliva 1972; Saunders et al. 1974). The stimulus responsible for stimulating the central chemoreceptors is thought to be either the carbon dioxide molecule or the hydrogen ion. In non-respiratory acid-base disturbances the inverse relationship between hydrogen ion concentration and Paces in vivo is now well established (Van Ypersele et al. 1973; Bone et al. 1974; Stoker et al. 1975). The relationship is a curvilinear one and differs only in the mathematical equations that express these curves. In non-respiratory acid-base disturbances the respiratory drive would appear to be related to the hydrogen ion concentration and not the Paces, as exemplified by the patient discussed. The values of hydrogen ion concentration and Paces in the case reported here fit the values predicted by Bone et al. from their graph constructed from their own data and data derived from the literature. Patients with carbon dioxide retention and chronic lung disease are known occasionally to become alkalaemic (Robin 1963). In this case the possibility of chronic lung disease was made highly improbable by applying the alveolar gas equation to the blood gas values on admission. Inspired air normally has a POZ of about 20 kPa (1.50 mmHg). The sum of the Pa02 and Paces of 18.6 kPa (139 mmHg) indicates that the alveolararterial Po2 difference and hence the venous admixture was well within normal limits for a 53-year-old man. It is apparent from a review of the other cases reported (Table I) that the cause of the alkalosis in each case where clinical details are given, except one with a stroke, was loss of acid from the stomach. There are no cases of significant hypoventilation occurring in alkalosis due to potassium deficiency. The intracellular hydrogen ion concentration in rats during the development of hypokalaemic alkalosis has been ,found to remain constant (Campion et al. 1968). In normal subjects made alkalotic by either potassium deficiency or hydrogen ion deficiency, the potassium deficiency group did not hypoventilate whereas the hydrogen ion deficient group hypoventilated (Goldring et al. 1968). It would seem reasonable to postulate that it is the fall in intracellular hydrogen ion concentration that is responsible for the hypoventilation in those cases which have lost acid and that the hypokalaemic group do not hypoventilate because the intracellular hydrogen ion concentration remains constant. Goldring et al. postulated this on the basis of their experiments but the degree of hypoventilation achieved was minimal in comparison to those levels found in patients quoted in this paper.

64

Jonathan Webb

Table

I. Reported cases (55 mmHg)

of non-respiratory

Source

alkalosis

and

hypoventilation

Hydrogen concentration

Aetiology

(nmol/litre Kennedy Kildeberg

et al. (1949) (1963)

Eichenholz

Pyloric obstruction 178 observations

et al. (1964)

Pyloric Pyloric Pyloric

Stinebaugh and Austen (1967) Thomford et al. (1968) Goldfinger (1969) Tuller and Mehdi (1971)

* On

added

inspired

a Paces

obstruction obstruction obstruction

38 29 38 26 35 32 in 8 cases with 28 28 24 33 29

>

7.3

kPa

ion Paces (pH))

26 (7.59) in 20 children with pyloric stenosis (55 mmHg) in 11 readings 26 (7.60) 21 (7.67) 29 (7.54)

Stenosis of gastroileostomy Vomiting? + diuretics Vomiting Pyloric obstruction Stroke + diuretics Vomiting No clinical details Pyloric stenosis Gastric aspiration Pyloric stenosis No clinical detail Pyloric stenosis

Oliva (1972) Jarbol et al. (1972) Shear and Brandman (1973) Saunders et al. (1974) Bone et al. (1974) Williams (1976)

with

@‘a)

(mmHg)

7.87 Pacoa

59.0 > 7.3 kPa

7.36 7.53 7.40

55.2 56.5 55.5

(7.43) 8.60 64.5 (7.55) 8.67 65 (7.43) 8.00 60 (7.60) 9.34 70 (7.46) 8.27 62’ (7.50) 10.00 75 Paces > 7.3 kPa (55 mmHg) (7.56) 8.94 67 (7.56) 11.73 88” (7.62) 10.00 75 (7.49) 7.73 58 (7.54) 9.4 70

oxygen. VOMITING

Initially

High renal

plasma tubular

t in NaHCO’ distal tubule3 Na exchange

GENERATION

Steady

/

HCO; exceeds reabsorotion

\

HCO; I

Loss of chloride

{ amou;t of NaHCO, presenting to distal tubule

K+ and

I Normal acid urine with low K’ and Na’

AND

H’

MAINTENANCE

OF

METABOLIC

I

reabsorption

to

presented

for

Renal

state

ALKALOSIS

Contraction of ECF volume and decrease Clavailable for reabsorption in proximal tubule. I Stimulation of Na reabsorption from proximal and distal tubules “in defence” of ECF volume.

-

MECHANISMS

SUGGESTED

The generation and maintenance of non-respiratory alkalosis is comprehensively reviewed by Seldin and Rector (1972). It is a complicated and poorly understood subject but some insight comes from the work of Kassirer and Schwartz (1966), who have shown in man that selective depletion of hydrochloric acid in the presence of a low salt diet results in a persistent alkalosis with augmented potassium excretion and a normal sodium balance. This state was remedied when dietary chloride was restored to normal.

Hypercapnia with Non-respiratory

Alkalosis

65

The explanation given for these findings was that sodium normally enters the glomerular filtrate at about 140 mmoljitre and chloride at 115 mmoljitre. In the presence of a low chloride concentration the kidney could either excrete more sodium than usual because of the lack of anion to accompany it during reabsorption, or reabsorb the sodium and increase the hydrogen and potassium exchange, and so excrete more hydrogen and potassium than normal but maintaining sodium balance. The latter alternative seems to be the case. Bicarbonate reabsorption increases linearly, with Paces (Rector et al. 1960) and so the respiratory compensation in those cases serves to hinder the renal compensation. Hypokalaemia and contraction of the extracellular fluid volume increases bicarbonate reabsorption (Seldin & Rector 1972; Rector et al. 1960). During the period of vomiting the fall in hydrogen ion concentration is due to loss of hydrochloric acid from the stomach, the bicarbonate concentration rises and it is postulated that in the initial stages bicarbonate reabsorption by the kidney fails to match the rise in bicarbonate concentration, and so an increase in sodium bicarbonate presented to the distal tubules stimulates increased sodium potassium exchange with the result that the urine contains more sodium potassium and bicarbonate and so the urine is initially alkaline. As the renal bicarbonate reabsorption increases as a result of the factors already mentioned the amount of sodium, chloride and bicarbonate presenting to the distal tubule is much less with the result that urinary excretion of sodium potassium and chloride is very low, and the urine hydrogen ion concentration is normal (paradoxical aciduria). This theory was borne out by the drainage studies carried out by Kassierer and Schwartz (1966). ACKNOWLEDGEMENTS I would like to thank Dr Victor Parsons for allowing me to publish this case and Dr Tim

Clark for his helpful comments during the preparation

of the discussion.

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KENNEDY, T. J., jun., WINKLEY, J. H. & DUNNING, M. F. (1949) Gastric alkalosis with hypokalaemia. Am. J. Med. 6, 790. KILDEBERG, P. (1963) Respiratory compensation in metabolic alkalosis. Acta med. scund. 2 74, 515. OLIVA, P. B. (1972) Severe alveolar hypoventilation in a patient with metabolic alkalosis. Am. J. Med. 52, 817. RECTOR, F. C., jun., SELDIN, D. W., ROBERTS, A. D., jun. & SMITH, J. S. (1960) The role of plasma COs tension and carbonic anhydrase activity in the renal reabsorption of bicarbonate. J clin. Invest. 39, 1706. ROBIN, E. D. (1963) Abnormalities of acid-base regulation in chronic pulmonary disease, with special reference to hypercapnia and extracellular alkalosis. New Engl. J. Med. 268, 917. SAUNDERS, N. A., CARTER, J., SCAMPS, P. & VANDENBERG, R. (1974) Severe hypercapnia associated with metabolic alkalosis due to pyloric stenosis. Aust. N.Z. J. Med. 4, 385. SELDIN, D. W. & RECTOR, F. C., jun. (1972) The generation and maintenance of metabolic alkalosis. Kidney International 1, 306. SHEAR, L. & BRANDMAN, I. S. (1973) Hypoxia and hypercapnia caused by respiratory compensation for metabolic alkalosis. Am. Rev. resp. Dis. 107, 836. STINEBAUGH, B. J. & AUSTIN, W. H. (1967) Acid-base balance. Archs intern. Med. 119, 182. STOKER, J. B., KAPPAGODA, C. T., SNOW, H. M. & LINDEN, R. J. (1975) The assessment of acidbase disturbance in man by the use of carbon dioxide titration curves. Clin. Sci. molec. Med. 48, 133. THOMFORD, N. R., BACHULIS, B. L. & BRASHEER, R. E. (1968) Stenosis of an inadvertent gastroileostomy with severe metabolic alkalosis. Ann. Surg. 167, 595. TULLER, M. A. & MEHDI, F. (1971) Compensatory hypoventilation and hypercapnia in primary metabolic alkalosis. Am. J. Med. 50, 281. VAN YPERSELE DE STRIHOU, C. & FRANS, A. (1973) The respiratory response to chronic metabolic alkalosis and acidosis in disease. C&n. Sci. molec. Med. 45, 439. WILLIAMS, S. E. (1976) Hydrogen ion infusion for treating severe metabolic alkalosis. BY. med. J. 1. 1189.