Hepatic porphyria
Acute intermittent porphyria
Acute intermittent porphyria - A hereditary disease, characterized by lesions of the central and peripheral nervous system, abdominal pain, increased blood pressure and release pink urine due to the large number of porphyrins in its predecessor - porphobilinogen.
Etiology and pathogenesis of acute intermittent porphyria
The disease is inherited in an autosomal dominant pattern.
The pathogenesis lie, most likely, violation of the activity of the enzyme synthase isomer I uroporphyrinogen and increased activity of nitric δ-aminolevulinic acid. Clinical manifestations of the disease are related, obviously, the accumulation in the nerve cells of toxic substances - δ-aminolevulinic acid.
As research, δ-aminolevulinic acid is concentrated in the hypothalamus of the brain and inhibits the activity of Na / K-dependent adenozinfosfatazy, which leads to disruption of ion transport through membranes, disrupts the function of the nervous tissue. Maybe, that the toxic effects associated with exposure to the nerve cells not only δ-aminolevulinic acid, but other monopirrolov. This results in demyelination of nerve fibers, developing axonal neuropathy, which is responsible for all clinical manifestations of the disease.
Clinical manifestations of acute intermittent porphyria
The most characteristic symptom of acute intermittent porphyria is abdominal pain. Sometimes it is localized in the epigastric, Recalling picture perforated ulcer. The pain may be localized in the right inguinal region, simulating a picture of acute appendicitis; in the right upper quadrant, Recalling the pain of gallstones; in the lumbar region, forcing suspected renal colic, Sometimes an ectopic pregnancy, because of severe pain often precedes menstruation delayed. Often these patients operate, However, the operation does not allow to locate the source of pain, and often does not lead to the relief of the patient.
For acute porphyria is characterized as disorders of the peripheral nervous system by type of polyneuritis. Perhaps the defeat and the central nervous system, manifesting convulsions, epileptiform seizures, delirium, hallucinations. Sometimes develops blindness.
A significant part of patients show increased blood pressure, sometimes a marked increase with hypertension as a systolic, and diastolic blood pressure.
A characteristic feature of acute intermittent porphyria – urine pink, and sometimes red, especially in the period of exacerbation.
The flow of porphyria can be different.
Most often, the disease manifests itself in young women, Girls. It provokes pregnancy, delivery, taking a number of drugs: ʙarʙituratov, sulfa drugs, analigina. Particularly strong exacerbation occur after surgery, when used for sedation thiopental sodium.
In these cases, before the operation the patient complains of a severe pain in the abdomen, and after the operation he develops pronounced neurological disorders, want to control breathing.
Exacerbates the disease can receive a number of drugs, soderzhashtih phenobarbital - valokordina, bellaspona belloïda, teofedrina. Besides, aggravation of this form of porphyria can occur under the influence of female hormones, antimikoznyh drugs - griseofulvin.
After the acute illness, of severe neurological disorders, death can occur, but sometimes neurological symptoms gradually decreases and there comes remission. Therefore, the disease is called acute intermittent porphyria. New aggravation may occur spontaneously, as well as under the influence of drugs or certain chemicals, especially chlorophos.
Clinical manifestations of the disease are noted not all carriers of the abnormal gene. Often, relatives of patients, particularly males, biochemical signs of the disease are detected in the absence of clinical signs (latent form of acute intermittent porphyria). Do such persons under the influence of unfavorable factors may occur severe exacerbation.
Diagnosis of acute intermittent porphyria
Diagnosis of acute intermittent porphyria is based on the finding in the urine of patients with precursor synthesis of porphyrin - porphobilinogen and δ-aminolevulinic acid. For this purpose the quantitative Mauzerall sample and Granick determination of these substances in the urine sample and qualitative, which is as follows. In the test tube to 1-2 ml of fresh urine of the patient was added an equal amount of Ehrlich's reagent (2 % solution paradimetil-aminobenzaldehyde, dissolved in 4% hydrochloric acid). If there appears a cherry porphobilinogen- red color. The same staining can be observed in large amounts in the urine urobilin. To clarify the nature of the change to a mixture of urine and the reagent is added to an equal amount of chloroform. After settling at the bottom of chloroform is, and the aqueous layer from above. If the stain is associated with urobilin, it goes to the lower layer of chloroform, porphyria color remains at the upper aqueous layer.
Hereditary coproporphyria
Hereditary coproporphyria - rather a rare form of porphyria. It was described in 1955 g. According to clinical manifestations reminiscent of acute intermittent porphyria.
The etiology and pathogenesis of hereditary coproporphyria
The disease is inherited in an autosomal dominant. Often it occurs latently. When an infringement of hereditary coproporphyria enzyme activity coproporphyrin- genoksidazy. When this increased activity in the liver synthesis δ-aminolevulinic acid.
The defeat of the nervous system associated with the hereditary coproporphyria, obviously, also with the accumulation of δ-aminolevulinic acid or any pyrrole compounds.
Clinical manifestations of hereditary coproporphyria
The most common symptom is pain in the abdomen, sometimes marked mental disorders, paresis, but they are more rare and not so much expressed, as in acute intermittent porphyria. May increase blood pressure, is a tachycardia. In some patients, there are signs of bullous photodermatitis.
Most patients with hereditary coproporphyria observed abdominal pain, some patients revealed increased sensitivity to solar radiation. Perhaps the development of paresis, Mental Disorders, the presence of epileptic seizures. In some patients, there is a slight increase in body temperature, hypertension, tachycardia, vomiting, constipation.
Laboratory tests at hereditary coproporphyria
In the urine of patients with hereditary coproporphyria found in acute increase in the number of δ-aminolevulinic acid and porphobilinogen, although to a lesser extent, than in acute intermittent porphyria.
The urine and feces dramatically increased the number of coproporphyrin. Contents uroporphyrin protoporphyrin in urine and in the feces within the normal range. The number of red blood cells is not increased porphyrins. In remission maintenance of porphobilinogen and δ-aminolevulinic acid can be normal, however, the level of coproporphyrin in urine and feces and remains elevated during remission.
Variegated porphyria
Variegated porphyria is characterized by symptoms of acute intermittent porphyria, and symptoms of skin lesions.
The etiology and pathogenesis of porphyria variegated
The disease is inherited in an autosomal dominant. At the heart of its pathogenesis is, apparently, violation of the activity of the enzyme protoporphyrinogen, responsible for the synthesis of protoporphyrin protoporphyrinogen. This is an increase in the synthesis of δ-aminolevulinic acid by increasing the activity of nitric δ-aminolevulinic acid.
Clinical manifestations of variegated porphyria
The disease occurs in both sexes, but manifestations of skin lesions are often observed in men, and signs of acute porphyria - women. Abdominal pain, neurological symptoms, as well as in acute intermittent porphyria, occur under the influence of barbiturates, sulfa drugs, analigina, griseofulvin.
When variegated porphyria, Unlike acute intermittent form, sometimes develop kidney failure. Neurological symptoms can be very severe.
Laboratory findings in the variegated porphyria
Characteristically a significant permanent increase in the protoporphyrin in stool of patients. During exacerbation number of δ-aminolevulinic acid and porphobilinogen increased, However, after the improvement of the patient, reducing stomachache, neurological symptoms significantly reduced, and sometimes it is quite normal.
Urokoproporfirii – Late each porphyria
Urokoproporfirii (Late each porphyria) - The most common form of porphyria. It is characterized by skin lesions symptomatic, appearing most frequently in older age 40 years.
Etiology and pathogenesis urokoproporfirii
Until now, the cause and mechanism of urokoproporfirii finally installed. Known, that the disease is often seen in persons, abusing alcohol, It has suffered in the past hepatitis, had contact with hepatotoxic poisons, and in individuals, occupational exposed to gasoline, eg from drivers.
The majority of people with porphyria there is a violation of the functional state of the liver. All this gives grounds to assume, what urokoproporfirii - not hereditary, and acquired form of porphyria. However it is known, that only a small proportion of persons, abusing alcohol, ill porphyria. Besides, in severe forms of hepatitis in the urine increases the content coproporphyrin, instead uroporphyrin, whereas urokoproporfirii in urine increased mainly content uroporphyrin, and the number is increasing slightly coproporphyrin. The majority of the relatives of patients urokoproporfirii uroporphyrin found an increased content in urine and feces in coproporphyrin.
Clinical manifestations urokoproporfirii
The most characteristic features urokoproporfirii include increased sensitivity to light mechanical trauma, solar radiation, hypotryhoz, pigmentation changes (as a reduction in, and increase its), diffuse thinning or thickening of the skin, so-called psevdosklerodermiya.
Increased sensitivity to mechanical trauma manifests itself on the skin of the fingers, person, Neck. On the back of the hand after an injury or after the bubble, resulting from sun exposure, painted small scars remain. For urokoproporfirii prosopodobnye retention cysts characteristic rounded shape with a diameter less than 5.1 mm on the skin of the fingers, sometimes on the face.
Perhaps atypical for urokoproporfirii as sklerodermopodobnoy form, in which there is an alternation of areas of hyperpigmentation and depigmentation of the skin and seal with subsequent atrophy, as well as the typical scleroderma waxy shine of the skin and whitish-yellow color.
When melanodermicheskoy form of porphyria has been a significant darkening of the skin without overt signs photodermatosis.
It is characterized by enlargement of the liver to urokoproporfirii, which is often accompanied by violation of its functional state.
Quite often mixed form of porphyria diagnosed without any reason when a patients urokoproporfirii abdominal pain or slight neurological symptoms. However, patients urokoproporfirii often abuse alcohol, that can cause these symptoms. Therefore, the diagnosis of porphyria and hereditary variegated coproporphyria necessary to conduct special studies.
Laboratory tests at urokoproporfirii
When urokoproporfirii uroporphyrin content in urine increased to 2000-10000 ug 1 g creatinine at a rate of up to 20 ug 1 g. The content also increased coproporphyrin, but to a much lesser extent - to 300-800 ug 1 g creatinine at a rate of 20-80 ug 1 g. Therefore, it is not enough to explore the content coproporphyrin, as is the practice in many laboratories, when the answer is given in points. This research is often misinformed doctor, since Porfirio mostly content increases uroporphyrin, and the number is increasing korproporfirina lead poisoning and hepatitis.
The content of porphobilinogen and δ-aminolevulinic acid in the urine and the number of red blood cells in patients with porphyrins urokoproporfnriey within normal limits. The content of porphyrins in the stool may be normal, especially in the period of exacerbation. While improving the condition of patients the number of porphyrins in stool (coproporphyrin and protoporphyrin) may increase.
