Porphyria Alcohol

ALAD, an enzyme occurring early in the heme pathway, is also considered a sensitive indicator of lead effect (Hemberg et al. 1970 Morris et al. 1988 Somashekaraiah et al. 1990 Tola et al. 1973). Because there is no well-defined blood lead threshold at which inhibition of ALAD does not occur, it allows measurement of the effect on the general population at environmental lead levels and does not require high exposure levels as with occupational workers (Hemberg et al. 1970). However, ALAD activity may also be decreased with other diseases or conditions such as porphyria, liver cirrhosis, and alcoholism (Somashekaraiah et al. 1990). 

When used for detoxification, phenobarbital is given in equal doses four times a day. The maximum daily dose of phenobarbital is 600 mg, but much lower doses are usually sufficient. The phenobarbital dose is lowered (i.e., tapered) by about 20% per day. If the patient is too drowsy, then a dose should be skipped. If breakthrough withdrawal symptoms continue to occur, then the pace of the detoxification should be slowed. Before using phenobarbital, liver function tests should be obtained. All barbiturates depend greatly on the liver to be metabolized. Alcoholics with cirrhosis or other forms of liver impairment may have difficulty clearing phenobarbital. Phenobarbital should not be used in patients with poor liver function. In addition, the barbiturates can worsen a medical condition known as porphyria and should be avoided in those with this disorder. Phenobarbital, as noted, is seldom used today for alcohol detoxification. 

Typical pathological values show a strong pink color. Other colors should not be interpreted. Values elevated at least fivefold are proof of acute porphyria. Lower, but still increased values may be encountered in asymptomatic porphyria patients and as a secondary phenomenon due to alcohol intake or stress. PBG elevation is apparently more specific for porphyria. 

Symptomatic porphyria patients usually show urinary porphyrin concentrations that exceed the upper limit of normal by twofold or more. Table 7.3.1 lists most of the diagnostic abnormalities of the different porphyrias. Only slightly abnormal or even fully normal values may be seen in asymptomatic patients. But alcohol overconsumption, enzyme-inducing drugs, stress, and other factors may also induce slightly abnormal values that should not be mistaken for porphyria. A characteristic sign for such a secondary effect is the isolated elevation of coproporphyrin, especially of its... 

Harden, L., Bengtsson, N.O., Jonsson, U., Erikssonn, S. Larsson, L.G. (1984) Aetiological aspects of primary liver cancer with special regard to alcohol, organic solvents and acute intermittent porphyria—an epidemiological investigation. Br. J. Cancer. 50, 389-397... 

Benzodiazepines also should not be taken by people who have a history of alcohol or drug abuse, stroke or other brain disorder, chronic lung disease, hyperactivity, depression or other mental illness, myasthenia gravis, sleep apnea, epilepsy, porphyria, kidney disease, or liver disease. 

Elevated iron, which usually corresponds to increased ferritin, is found primarily in idiopathic haemochromatosis and secondarily in acute viral hepatitis, liver cell necrosis and necrotic episodes, alcoholic liver diseases, porphyria cutanea tarda, oestrogen administration, etc. 

The clinical course can be unfavourably affected by various risk factors (e.g. race, gender, advanced age, immune status, genetics) as well as by alcohol abuse (275, 337, 363), toxins, coinfections and chemicals. Conversely, the course and prognosis of HBV, HDV and HIV infections as well as of metabolic diseases (e.g. porphyria cutanea tarda, ai-antitrypsin deficiency) can deteriorate as a result of hepatitis C. 

Primary porphyrias are caused by hereditary enzyme defects in haem synthesis. They can be differentiated clinically into acute and chronic porphyrias as well as pathogenetically into hepatic and erythropoietic porphyrias. Secondary porphyrias are symptomatic porphyrias present in various diseases or caused by poisoning or chemical substances, particularly alcohol. Depending on the preferred manifestation site of the enzyme defect, either in the hepatocytes or erythrocytes (bone marrow), the porphyrias are subdivided into hepatic, erythropoietic and hepatoerythropoietic forms. However, this classification is not always strictly applicable. Based on the course of disease, acute and chronic forms may be differentiated in primary hepatic porphyrias. The acute form is characterized by a congenital reg-... 

Hepatic porphyrias show the following characteristics (1.) intermittent course, (2.) increased ALA synthase activity, and (3.) acute attacks induced or manifesting during the latency period due to numerous causes such as alcohol (281), hunger, carbohydrate deficiency, hormones, stress, intoxication, metabolic products and medicaments, (s. tab. 31.13) The diagnosis is based upon the clinical symptomatology and the excretion pattern of the porphyrins or their precursors in the urine and faeces as well as their concentrations in the erythrocytes and plasma, (s. tab. 31.14)... 

Fig. 31.19 Chronic hepatic porphyria Sonographically, multiple, ring-shaped foci with marginal hyperechoic ring and central hypo-echoic reflexes. (Completely reversible after alcohol abstinence)...

These foci result from porphyrin deposition and are often only discovered by chance since there is no evidence of a chronic porphyria. They can be mistaken for tumours or metastases neither the foci nor their neighbouring parenchyma are hypervascularized. Following abstinence of alcohol and avoidance of oestrogens, they are completely reversible. In a chronic porphyria, there is frequently a uniform increase in density due to diffuse porphyrin storage. 

Differential diagnosis The following conditions should be excluded (7.) alcohol-induced liver disease, (2.) primary biliary cholangitis (86), (3.) porphyria cutanea tarda (108), and (4.) autoimmune hepatitis (89) or autoimmune cholangitis (132) associated with anti-HCV. 

Neonatal adrenoleucodystrophia Nieman-Pick disease Non-alcoholic steatohepatitis Porphyria cutanea tarda Seip-Lawrence syndrome Thalassaemia Tyrosinosis (type I)... 

Abdominal pain, weakness, confusion after ingestion of alcohol or barbituates Anxiety Porphyria... 

Barbiturate sensitivity alcohol pregnancy (FDA category D) manifest or latent porphyria severe respiratory disease when dyspnea or obstruction is evident nephritic patients. 

Porphyria maybe classified as hepatic or erythropoietic. However, enzyme defects are sometimes common to both tissues. Porphyrias can be induced by alcohol, stress, infection, starvation, hormonal changes (e.g., menstruation), and certain drugs. These drugs presumably precipitate acute manifestations in susceptible subjects since they are inducers of cytochrome P-450 and increase the need for synthesis of heme as they deplete the mitochondrial pool of free heme. Major hepatic porphyrias include acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and porphyria cutanea tarda. The principal erythropoietic porphyrias are hereditary erythropoietic porphyria and erythropoietic protoporphyria. 

Excretion of zinc in urine (0.3-0.6 mg/d) is independent of dietary intake. It is increased in renal disease, in alcoholic cirrhosis, in hepatic porphyria, following major operations, in severely burned patients, and in response to treatment with ethylenediaminetetraacetic acid. 

Neuropsychiatric, neuromuscular, autonomic dysfunction, and intense abdominal pain characterize AIP. In the liver, this enzyme deficiency results in the increased inducibility of abnormal heme intermediates by certain drugs. Drugs and agents known to induce hepatic cytochrome P450 enzymes or to increase hepatic heme mrnover are theoretically capable of precipitating porphyria. Barbiturates, estrogens, alcohol, and heavy metals such as lead have been documented to induce porphyria in genetically susceptible people. ... 

Doss M, Baumann H, Sixel P. Alcohol in acute porphyria. Lancet 1982 1 1307. 

Other conditions Porphyrias, pregnancy, cystinosis, cystinuria, kidney disease, smoking, alcohol consumption, gout... 

Porphyria cutanea tarda, characterized by fluid-filled vesicles and bullae on sun-exposed areas, can be either genetic or associated with alcohol abuse or hepatitis C. Although the associated iron overload is treated with phlebotomy, the dermatologic manifestations sometimes are treated with antimalarial agents. These patients require reduced doses because of the potential for hepatotoxic-ity, as manifested by elevated transaminase levels, and the rapid excretion of large amounts of uroporphyrins in the urine that can occur with usual doses. Low-dose twice-weekly administration is effective and avoids these side effects. 

Lead poisoning can affect the heme metabolic pathway at several sites, and this generally leads to an increase in the zinc protoporphyrin level of red blood cells. In fact, by measuring the fluorescence emission from red cell zinc protoporphyrin, it is possible to screen large populations for lead poisoning. Other substances that can affect the Ever, producing porphyria-like symptoms, are barbiturates, DDT, and alcohol. 

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