Porphyria

PORPHYRIA, the excretion of porphyrin pigment with urine, which in chemical structure represents a non-iron derivative of heme, more precisely of hemin. Until relatively recently, the excretion of porphyrin with urine was called hematoporphyrinuria, as it was believed that hematoporphyrin was being excreted. However, recent research has shown the error of such a view, since hematoporphyrin (C₃₄H₃₈N₄O₆) does not occur in the body under either normal or pathological conditions, but represents an artificial product of the action of concentrated mineral acids on blood and hemin. Research by Fischer showed that uroporphyrin and coproporphyrin are excreted with urine (see Porphyrin). These two natural porphyrins are close in their chemical and spectroscopic properties to a number of others (artificially obtained), such as: hematoporphyrin, mesoporphyrin, protoporphyrin, etioporphyrin, etc. Increased excretion of porphyrins is a pathological symptom observed in certain intoxications, infectious diseases, internal hemorrhages, severe anemias and liver cirrhoses. It is also observed in P. as a congenital disease (see below). Various assumptions have been expressed regarding the place and sources of origin of porphyrins in the body: the formation of porphyrin in tissues during hemorrhages was considered possible, the role of the bacterial flora of the intestine was acknowledged. Some considered porphyrins an intermediate product in the breakdown of heme in the process of formation of bile pigments. The possibility of the synthetic formation of porphyrins in the body was also indicated. Porphyrins usually color fluids and tissues purple or cherry-red color. In mild P., urine sometimes retains its usual color and only upon standing in light or upon oxidation acquires a red color. This is explained by the excretion of colorless porphyrinogen (C₃₄H₄₄O₄), which turns into porphyrin in light and with access to oxygen. The presence of porphyrins in the body causes increased sensitivity to light, manifested as hyperemia, itching, infiltration and swelling of the skin and even burns occurring under the influence of light. This photosensitizing property of porphyrins is related to their ability to fluoresce, to their optical activity. The photosensitizing effect of different porphyrins varies and, according to Fischer's observations, increases with the number of carboxyl groups. Thus, uroporphyrin has the maximum, coproporphyrin less, and hematoporphyrin the weakest sensitizing influence. Clinically, several forms of porphyria are distinguished. Gunther (1912) described the so-called hereditary P. (see Hematoporphyrinuria). The so-called acute P. (porphyrinuria acuta) represents a symptom of a rather severe toxicosis of unclear etiology. It is observed between the ages of 7 and 50 years, more often in women than in men (12:1). At the center of the clinical picture of this form of P. are colicky pains in the abdomen, vomiting, constipation, excretion of dark red urine and a number of nervous phenomena. The pains are localized in the epigastrium or spread throughout the abdomen, can simulate appendicitis, renal colic, pancreatitis, ileus. Sometimes P. is accompanied by bloody vomiting and melena, simulating a peptic ulcer. The characteristic color of urine helps in these cases in differential diagnosis. However, as noted above, such coloration may sometimes be absent (excretion of porphyrinogen) _g which makes the diagnosis of the disease very difficult. Radiologically, it is sometimes possible to establish atony and expansion of the stomach and duodenum during phenomena of severe spasm in the small intestines. Among the nervous symptoms, drowsiness, phenomena of motor excitability, sometimes signs of acute polyneuritis and even paralysis are noted. The duration of an attack is from 4 days to 1 month. Recurrences are often observed. No increased sensitivity to light is noted in acute P. The prognosis of the disease is serious. The presence of toxic effects on blood with the formation of unusual products of hemolysis is considered probable. The clinical picture, close to the described one, is given by acute toxic P. as a result of prolonged use of sulfonal and trional. In these cases, constitutional factors play a special role, since prolonged use of these hypnotics, as is known, does not always lead to P. - Greater practical and particularly diagnostic significance has P. in chronic lead poisoning. In these cases, the constant presence of porphyrin in urine is observed, the amount of which increases during the so-called lead colics, reaching in severe cases 3-4 mg per 1 liter of urine. The literature presents assumptions (Gelman) on the pathogenetic role of porphyrin in the appearance of lead colic, which has a similar clinical picture to the acute P. described above. It should be noted that during lead crises, only coproporphyrin is found in urine, while in other P. uroporphyrin is also encountered. There are indications of the appearance of P. in poisonings with zinc, aniline and nitrobenzene. Gunther described cases of P. having an intermediate clinical picture between the congenital and acute hereditary form of P. The so-called chronic P. The disease occurs at any age, proceeds in the form of separate attacks, accompanied by both pains in the abdomen and photosensitivity with skin phenomena. Porphyrin is best detected in urine by Fischer's method, which consists in the fact that coproporphyrin is extracted with ether after adding glacial acetic acid to the urine and is examined spectroscopically. Uroporphyrin is detected in the precipitate of urine phosphates (after adding caustic soda) by washing the precipitate with alcohol, dissolving it in hydrochloric acid and spectroscopy (method Garrod). An acidic solution of porphyrin has 2 absorption bands in the spectrum: one narrow, less distinct, at the boundary between the yellow and orange parts of the spectrum, another broader band near the yellow and green parts of the spectrum. An alkaline solution of porphyrin gives 4 absorption bands: in the orange, yellow, yellow-green and green parts of the spectrum. Quantitative determination of porphyrin is based on diluting with hydrochloric acid the precipitate of phosphates obtained in the above-mentioned Garro method until the spectrum almost completely disappears. The amount of porphyrin is judged by the degree of dilution (see also Urine, urine analysis).