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ultracentrifugal separation of serum-iron into ferritinand transferrin fractions.11 The appearance of

isotope in the ferritin fraction was studied in the ratafter administration of various 59 Fe-labelled pre-cursors (transferrin, haemoglobin-haptoglobin, andheat-treated red blood-cells injected intravenously,and ferrous chloride administered by gastric tube)and in man during routine ferrokinetic investigations.The ferritin fraction became labelled, in the rat,only after intravenous injection of the 59Fe-labelled,heat-treated red cells. After initial uptake of 59Fe,largely by the spleen, the peak labelling of plasma-ferritin was reached within 30 minutes after injec-tion. Peak labelling of the transferrin fraction wasat two hours, after 59Fe-ferritin had been cleared bythe liver. These results indicate that serum-ferritiniron comes from the reticuloendothelial system,where it derives partly from senescent red cells. It isthen transported almost entirely to the hepatocyte.Transferrin, on the other hand, seems to be theexclusive carrier of iron from the liver parenchymalcell and the intestine to the haematopoiedc cells ofthe bone-marrow. Work in the United Kingdomand the United States should soon provide moreinformation on the role of serum-ferritin in ironmetabolism and on the physiological basis for thenormal and abnormal changes in its concentration.The clinical value of the assay in relation to othermeasures of iron status-such as haemoglobin,haematocrit, red-cell indices, serum iron and ironbinding capacity, erythrocyte protoporphyrin, andstaining of marrow for iron-should also emergeover the next few years.

Polyps, Enemas, and ColonoscopesTHE advent of the double-contrast (Malmo) barium

enema some years ago led to the detection in the colonof polyps only a few millimetres in diameter. Butthis sometimes presented more problems than itsolved. Were they responsible for the symptoms ?Were they benign or malignant ? Should they beremoved; if so, how ? To identify a small soft

polyp from the outside of the bowel can be verydifficult, and laparotomy anyway seems an unneces-sarily big and risky way of removing a small benignlesion which may not be causing symptoms. Thepractice of many surgeons is to regard those less than1 cm. in diameter as benign and re-X-ray in threemonths to see if there has been any increase in size.

1

Those larger than 1 cm. are removed at laparotomyand colotomy (assuming that they are out of reachof the sigmoidoscope). Occasionally the adenomatouspolyps are multiple and familial and carry a high riskof malignancy. In these cases, all are agreed, a

1. Morson, B. C., Bussey, H. J. R. in Current Problems in Surgery(edited by M. M. Ravitch); p. 20. Chicago, 1970.

prophylactic total colectomy is indicated. Colono-

scopy with the new fibreoptic instruments has madea real contribution to the polyp problem. It is nowpossible to see, take biopsy specimens from, and oftenremove small polyps seen on a barium enema. Thestandard colonoscopes have four-way tip angulationand biopsy facilities, and the latest models have asnare deflector and C02 control or two channels andintegral stiffness control. These refinements makethe snaring of polyps easier. An insulated wire loopconnected to an electrical current, or a diathermysnare, is passed down one of the channels of thecolonoscope. Because of the risk of explosion frommethane in the bowel, most operators advise fillingthe bowel with C02 or some other inert gas.2 Oncethe polyp has been snared and removed, it must beretrieved by the snare or a basket, by sucking on tothe tip of the colonoscope, or by means of a subse-quent saline purge. In a series from the MayoClinic 3 26 (16%) of 158 polyps were not retrievedafter removal, and so the histology was not known;this proportion decreases with experience, and WOLFFand SHINYA 4 lost only 5% of 303 polyps.Most polyps turn out to be benign adenomas,3,4

but a few show malignant change. If this is super-ficial or carcinoma-in-situ, the endoscopic removal issufficient, with careful follow-up and repeat examina-tions. If there is invasive carcinoma (2-4%),3,4 it isright to advise surgical excision of the affected regionof the colon. Colonoscopy, it must be remembered,is not an end in itself but a means of treating patients.The barium enema remains the mainstay in investi-gating colonic disease because of its relative ease andsimplicity. As with colonoscopy, its success in

detecting small polyps depends on scrupulous bowelpreparation and careful technique. A barium enemashould be done before colonoscopy to help with theanatomy, to identify suspicious lesions, and to

diagnose associated diverticular disease which maymake the passing of the instrument more difficultand dangerous.There have now been several large series of fibre-

optic polypectomies,2-4 and the only importantcomplication has been perforation, which in experi-enced hands happened in less than 0-5%. Occasion-

ally there may be reactionary or secondary h2emor-rhage from the stalk of the polyp. It is certainly asafer and cheaper procedure than laparotomy andcolotomy for small polyps,5 and the patient can soonreturn to work. Colonoscopic polypectomy is not,however, an easy procedure for the casual operator.Like many useful techniques it needs practice andcan be very time-consuming at first: " There arefew more dangerous instruments than a probe with

2. Williams, C., Teague, R. Gut, 1973, 14, 990.3. Spencer, R. J., Coates, H. L., Anderson, M. J. Mayo Clin. Proc.

1974, 49, 40.4. Wolff, W. I., Shinya, H. New Engl. J. Med. 1973, 288, 329.5. Bloom, B. S.. Goldhaber, S. Z., Sugarbaker, P. H., O’Connor, N. E.

ibid. p. 368.

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no brains behind it."4 If complications are to bekept to a minimum, the procedure must be carriedout in a well-equipped room with X-ray facilitiesand experienced nursing assistance. A surgeonshould be available in case of complications, and thepatients should be prepared in such a way thatimmediate operation can be undertaken. Like all

fibreoptic instruments, colonoscopes can be damagedif they are not handled carefully and maintained andcleaned by trained staff, and repairs are expensive.Colonoscopy will play a major part in the treatmentof small colonic polyps, and the clinician, on seeinga polyp on barium enema, need no longer saywhimsically to himself " I wish I hadn’t found itbecause I don’t know what to do about it ".

HYPERURICAEMIC ACUTE RENAL FAILURE

ACUTE renal failure is a well-recognised complicationof severe hyperuricaemia. Less well known, however,is the fact that its pathogenesis has changed since thefirst accounts nearly fifty years ago. Most importantof all, this condition, commonly regarded as eitheruntreatable or not worth treating, is both eminentlytreatable and usually worth treating. Acute hyper-uricsemic renal failure is found in patients with

lymphomas and leukaemias, occasionally spontaneouslyas a result of rapid cell turnover but usually as acomplication of chemotherapy in which massive celldestruction suddenly liberates a large amount ofnucleic acids. In a review by Kjellstrand et al.,l themean plasma-uric-acid concentration at the time ofacute renal failure was 20 mg. per 100 ml., with arange of 12-36 mg. per 100 ml.l Patients whose acuterenal failure is an early manifestation of underlyingdisease must clearly be cured of renal failure beforedefinitive treatment can begin. But in the much

larger group whose renal failure is a complication oftreatment, effective prevention is the challenge;without it, and with increasingly aggressive chemo-therapy of these diseases, acute hyperuricasmic renalfailure may become much more common than it is now.When reviewed by Lilje up to 1966, acute hyper-

uricæmic renal failure carried a mortality of 47%.Since then treatment has become more aggressive andall sixteen patients reported between 1966 and 1971survived the acute renal failure. 1 If hyperuricaemicacute renal failure were a condition confined to

patients with almost immediately terminal disease,treatment would be pointless. In fact the mean ageof the patients reviewed by Kjellstrand was 28 years,and of the five patients treated in his unit one survived1 year and two others were still alive 11 and 15 monthsafter dialysis. The evidence in early reports pointedto ureteric obstruction by uric-acid crystals. All thefirst cases described by Bedma and Polcak in 1929 3had symptoms indicative of ureteric obstruction andall had a prompt diuresis after retrograde catheterisa-

1. Kjellstrand, C. M., Campbell, D. C., von Hartitzsch, B., Buselmeier,T. J. Archs intern. Med. 1974, 133, 349.

2. Lilje, E. Ugeskr. Laeger, 1970, 132, 12.3. Bedrna, J., Polcak, J. Med. klin. 1929, 25, 1700.

tion and ureteric lavage. A third of the patientsreviewed by Lilje also had symptoms suggestingurinary-tract obstruction. In contrast, presumptiveevidence of ureteric obstruction was found in onlyone case in the latest review 1—a patient reported byMaher and his colleagues 4 in whom uric-acid crystalswere seen protruding from the ureteral orifices.Even in that case the pathogenesis was probably notsimple ureteric obstruction, because ureteric lavageproduced no urine flow. Ureteric obstruction wasexcluded radiologically in three other patients, andKjellstrand’s own patients had neither symptomssuggesting obstruction nor uric-acid crystals in theurine. They all made a good recovery without anyinterference with the ureters. Existing evidencefavours the view of Reiselbach et alrs that acute

hyperuricsemic renal failure is caused by precipitationof uric acid in the distal tubules and collecting ducts(the sites of maximal acidification and concentrationof the urine); renal parenchymal damage is unlikelybecause of the rapid reversibility of the functionaldisturbance. The changing pathogenesis of thecondition is probably explained by differences in thepopulation of patients. In 1929, patients with acuteleukxmias and lymphomas died quickly, whether inrenal failure or not; only those with chronic diseasesurvived long, and it is this group of patients who areat risk from ureteric obstruction after prolonged hyper-uricaemia and hyperuricuria. None of the patientsin Kjellstrand’s review had chronic leukaemia andmost of them went into renal failure as a consequenceof chemotherapy (not with nephrotoxic drugs).Urgent rehydration and alkalinisation of the urine

is the first treatment for hypcruricaemic acute renalfailure, but if the patient is already oliguric the regimenmust be finely judged, and alkalinisation of the urinemay not be possible. If it fails there is little pointand some danger (of ototoxicity in particular) in givinglarge doses of intravenous diuretics. Unless the

patient is dehydrated the only effective treatment ishæmodialysis—a procedure between ten and twentytimes more efficient in this situation than peritonealdialysis. 1 With between two and five dialyses Kjell-strand’s patients rapidly recovered good renal functionwithin 3 weeks. Clearly the possibility of uretericobstruction must always be kept in mind, and theirrecommendation that ureteric catheterisation shouldbe carried out whenever symptoms suggest obstruction,or if no diuresis has been obtained after one week’streatment, must not be forgotten.Acute hyperuricaemia during chemotherapy cannot

entirely be prevented, but the severity can be kept toa minimum. Treatment with allopurinol should bestarted as long as possible before chemotherapy, toreduce pretreatment plasma-uric-acid, and it is wiseto continue with this agent indefinitely; the doseshould probably be substantially increased duringperiods of intensive treatment because allopurinol actsonly by competitive inhibition of xanthine oxidase-an effect which may therefore be swamped by a massiverelease of nucleoprotein. Although treatment with

4. Maher, J. F., Rath, C. E., Schreiner, G. E. Archs intern. Med.1969, 123, 128.

5. Reiselbach, R. E., Bentzel, C. J., Cotlove, E., Frei, E., Freireich,E. J. Am. J. Med. 1964, 37, 872.