Cholera and anuria

229 TRANSACTIONS OF 'rill,: ROYAL SOClE'rg O1: "tROPICAL MEDICINE AND HYGIENE. Vol. X X X V . N o . 4. January, 1942.

CHOLERA AND ANURIA BY

J. WALKER TOMB, O.B.R., M.I)., 1).P.[I.

ANURIA.

The four cardinal symptoms of cholera consist of purging, vmniting, muscular cramps and suppression of urine. According to WlNXOX (1937), when the systolic blood-pressure fails to 7.'; m.m. Hg., the secretion of urine ceases. RocErtS (1911) writes: " T h e most justly dreaded late complication of cholera is continued suppression of urine after reaction from collapse has taken place, as, unless it be of strictly limited duration, it leads to the supervention of uraemia combined with toxaemia." (The term " u r a e m i a " is used by ROGERS and his followers to connote anuria with urea-retention and is without its proper clinical significance.) HaLLIUUR'rOX and McDowALI, (1937) write: " U r a e m i a is the term given to the rapidly fatal state, commonly associated with unconsciousness, which results from severe disease of the kidney. The term was originally applied on the erroneous supposition that it is urea or some antecedent of urea which acts as the poison. There is no doubt that the poison is not any constituent of normal urine. If the kidneys of an animal are extirpated the animal dies in a few days, hut there are no uraemic convulsions. In m a n also if the kidneys are "healthy, or approximately so, and suppression of urine occurs

.~3()

CIIOI,ERA AND ANURIA.

from sinmltaneous blocking of both renal arteries by clot, or of both ureters by stones, again uraemia does not follow. On the other hand, uraemia may occur even while a patient With diseased kidneys is passing a considerable amount of urine. What the poison is that is responsible for the convulsions and coma is not known. It is doubtless some abnormal katabolic product, but whether this is produced by the kidney cells or in some other part of the'body is also unknown." LANGDON-BROWN and EVANS (1937) write: " Uraemia is the name which was given i n the past to the toxic state which complicates or terminates severe kidney disease and in which urea-retention occurs." More recently (they add) the name " non-renal uraemia " has been given to the high grade of urea-retention which may develop as a result of nonrenal factors. Amongst the most important of these factors are vomiting and diarrhoea, both of which cause urea-retention through loss of body fluids and the accompanying loss of chlorides. The symptoms of " choleraic uraemia,"i.e., anuria, are thus described by ROGERS (lOC. cit.): " T h e pulse remains above the normal rate and tends to increase instead of falling. More important is a quickening and deepening of the respirations which should at once put the physician on his guard and lead to the adoption of vigorous measures to try to avert the threatening calamity. Vomiting may recur, but it is not usually a marked symptom. " T h e skin is dry, and sweating may sometimes be difficult to producc in unfavourable cases. Diarrhoea may persist. " If the action of the kidneys cannot be restored the respirations become ntore and more laboured, restlessness ensues, and after a struggle for breath lasting for several days, gradual clouding of the intellect--deepening into coma, or cardiac failure--ends the scene." OSLER (1938) states: "Weakness, vertigo, nausea, dullness and drowsiness passing into coma, are the usual features of anuria. Vomiting is fairly common." The experimental administration of massive doses of urea causes a similar group of symptoms* (LANGOON-BRoWN and EvaNs, loc. cit.). The most prominent clinical symptoms of acute renal uraemia are severe headaches and mental disturbances, sudden amaurosis, convulsions and coma: a symptom-complex which is never met with in cholera. MECHANISM OF URINARY SECRETION.

Regarding the mechanism of urinary secretion HALLIBURTON and McDowALL (1937) state: " O n e fluid, the arterial blood, enters the kidncv: two fluids, the venous blood and the urine leave it. Both of these fluids arc different in composition from arterial blood. * Headache, giddiness, apathy, drowsiness, weakness, nausea and diarrhoea.

j. WALtCr.:R "rOMI~.

231

'" Wc know that il is not possible to convert any fluid into two others, each of different composition from itself, without an expenditure of energy which must come from somewhere outside the fluids themselves. In the kidneys, as in other secreting glands, this energy comes from the cells of the organ and the pressure of the arterial blood. The secretion of urine is therefore the result of work done hy 'the kidney. The quantity of work done may be measured within certain limits and the energy transformed by the kidneys may be estimated [in several ways]. "Estimations have heen made of the amount of oxygen used hy the kidney in secreting urines of known concentration. This oxygen may be taken as a measure of the amount of energy used by the organ. " The practical importance of these considerations lies in the fact that the expenditure of energy involves combustion, and combustion demands oxygen. For this reason an efficient supply of oxygen is essential ~o healthy kidney [function]. Regarding the secretory power of the glandular epithelium of the kidney tubules, H.aLLIBUaTOXand McDowaIJ, (loc. cir.) write: " In frogs the glomeruli can be cut out of action by ligaturing the renal arteries. The kidney is then supplied by the renal-portal vein, a vessel which goes to the tubules only. If urea is then injected under the skin, secretion of urine occurs which, though scanty in amount, is peculiarly rich in urea. Urea therefore in the frog is secreted by the epithelium of the tubules. In order to obtain this result, the kidney must receive sufficient oxygen for the maintenance of the functional activity of its cells. As the arterial supply is cut off by ligature of the renal arteries, this must be accomplished bv keeping the frog in an atmosphere of pure oxygen." POSTMORTEM

APPEARANCE OF KIDNEY IN CHOLERA.

With reference to the postmortem appearance of the kidney in cholera CrEa'rTE~JEE (1941) writes: " From the postmortem records of fifty-eight cases of cholera in the Carmichael Medical College Hospital [Calcutta], the gross appearance of the kidneys to the naked eye showed a marked congestion in 5 per cent., moderate congestion in 36 per cent., and a practically normal structure in 59 per cent." " Acute inflammatory changes are as a rule absent in the uraemic as well as in the non-uraemic kidney of cholera." The histological changes found in the kidney in so-called " uraemic" cases of cholera are thus described by CnaTaErq~v (Ioc. cir.): " The Malphigian corpuscles show great thickening and splitting of the basement membrane as well as non-inflammatory dilation and congestion of the capillaries of the glomerular raft. As a result, Bowman's capsule is seen to be more or less c~mlplerel.v filled tip. Similar swelling of the hasement membrane of the

232

C H O L E R A AND ANURIA.

tubules and dilatation of tile capillaries of tile medulla are also observed'" "Sometimes the cells of tile [convoluted] tubules might show degenerative changes " [30% in one series of cases--the proportion, doubtless, depending inversely on the resistance of the epithelial cells of the tubules to tissue-asphyxiation]. " T h e changes consist of a fatty degeneration of the [epithelial] cells of the convoluted tubules and also of a degenerative swelling of the cells, so that the lumen of the tubule is obliterated." COLLAPSE.

Since collapse of the circulation in consequence of the loss of body fluid is the outstanding symptom of fully-developed cholera, it will be profitable to consider the pathology of collapse. BAYLISS (1919) writes: " T h e second pathological state induced by prolonged low blood pressure in the capillaries is an increase in the permeability of the blood-vessels to colloids. Their normal state is one of impermeability te colloids, so that a solution of a colloid of sufficient osmotic pressure does not leave the circulation. If this property of the capillaries is lost, there is no force to retain fluid and both gum-saline and blood plasma escape into the tissues. The clinical index that such a state has been reached or is coming on is a progressive concentration of the blood as regards corpuscles. As long as the blood vessels maintain their normal state, the effect of a fall in blood pressure is to attract fluid from the tissues. This is because the osmotic pressure of the colloids remains at its normal height, wbile the filtration is reduced owing to the low arterial pressure. The result is a dilution of the blood, which is a favourable sign. " I f the increased permeability has not reached too high a value or not been present for too long a time, recovery is possible. It is evident, then, that the state is capable of return to normal, if not too serious. The renewed supply of oxygen restores the necessary impermeability to colloids." Regarding the collapse of the circulation, as observed in experimental animals, BAYLISS (loc. cir.) states that if treated shortly after onset recovery takes place, but if left for two hours or more recovery is impossible. O'SHAuGHNESSY and SLOME (1935) also state: " T h e r e is no satisfactory treatment of shock that has persisted for several hours. The subject of severe trauma who does not show some signs of recovery under established modes of treatment within two to three hours of his injury is almost inevitably doomed." CAUSE OF FAILURE OF SALINE TRANSFUSIONS.

The frequent failure of saline transfusions to restore and maintain the circulation in cholera, as well as to re-establish the secretion of urine, in cases

J. WALKER TOMB.

233

where the circulation has been successfully restored, is lhus seen to l)e due to irreversible change in the capillary endothelium, as well as in the epithelial cells of the kidney tubules, from lack of oxygen. RENAL FAILURE AFTER TRAUMATIC SHOCK.

In the condition known as " crush " injury, in which renal failure (anuria) is found to follow upon successful treatment of collapse of the circulation from traumatic shock after prolonged burial under d6bris consequent upon air raids, BZALL et al. (1941) report that the renal lesion in these cases "consists structurally of severe degenerative changes in the proximal convohlted tubules, and in the more distal parts of the nephron, brown pigmented casts. The matrix of the casts is thought to be composed of desquamated epithelial cells." RENNn~,, J. B. (1941), calls attention to two cases of renal lesions froln traumatic shock described by HUSI:ELDT and BJERLING(1937). Both patients sustained fracture of the pelvis and damage to soft tissues. Shock developed in both, yielding to transfilsion of citrated blood. Death occurred on the eighth day with a rising blood urea, hypertension, oedema (in one case), and general signs of " uraemm." The urine was very scanty, of low specific gravity, and contained casts and a few erythrocytes. Renal function tests gave very low results. At necropsy no injury to kidneys or urinary tract was fotmd. Microscopically the chief lesions were emptiness of the glomerular capillaries and degeneration of the epithelium of the tulmles (in some of which granular colonred pigment was present). It would therefore appear that the epithelial cells of the convoluted tubules are even more sensMve to want of oxygen than the endothelium of the blood capillaries itself. ~FREATMENT OF COLLAPSE.

Since lhe effects produccd by collapse of the circulation from any cause. including cholera, are directly referable to tissue-asphyxiation of the body-cells from want of oxygen (anoxia) I suggest that oxygen be administered where available (by B.L.B. mask) in all cases of collapse in cholera, after preliminary restoration of the circulation bv intravenous salines or bv salines with plasma. REFERENCES.

BAYLISS.W.M. (1919). Spec. Rep. Ser. *ned. Res. Com. No. 25. BEALL,D., BYWATERS,E. G. L., BELFREY, R. t{. R., MILES, J. A . R . (1941). Brit. reed. J., 1, 432.

CHATTERJEE, H. N. (1941). Trans. R. Soc. trop. Med. Hyg., 34, 333. HALLIBURTON,W. D. & McDOWALL, R. J. S. (1937). Handbook of Physiology & Biochemistry. 35th Ed. London: John Murray. HUSFELDT & BJERLING.(1937). Acta. Med. Scand., 91, 279 (quoted by J. B. RENNIE, loc. cit.)

234

CHOLERA AND ANI;RIA.

LANGDON-BROWN, W. & EVANS, G. (1937). Textbook of the Practice of Medicine. 5th Ed. Edited by F. W. PRICE. l , o n d o n : t t u m p h r e y Milford, Oxfl)rd Univcrsity Press. 214anson's Tropical Diseases. (1938). 10th Ed. Edited by P. MANSON-BAHR. London : Cassell & Co. ()'SHAUGHNESSY,L. F. & SLOME,D. (1935). Brit. J..S'urg., 22, 589. OSLER, W• &; MACRAE,T. (1938). Principles and Practice of:l/Iedicine. 13th Ed. I,ondon : Appleton• RENNIE, J . B . (1941). Brit. ,ned. J., 1,644. ROGERS, L. (1911). Cholera and its Treatment. London : Hodder & Stoughton, O×ford Medical Publications. • (1921). Bowel Diseases in the Tropics. London : Hodder 8: Stoughton, Oxford Medical Publications. ROSE, W. & CARLESS,A. (1937). Manual of Surgery. 15th Ed. Edited by WAKELI'.'Y, C. P. G. & HUNTER, J . B . London : BaiUi~re, Tindall & Cox. TOMB, J. W. & ~tiOMPSON, G . W . (1927). Trans. R. Soc. trop. Med. tlyg., 20, 516. (1927). Ibid., 21, 199. (1937). Lancet, 2, 1416. • (1941). S. A f t . med. J., 5~ lO9. \VINTON, F . R . (1937). Physiol. Rev., 17, 41)S.