Chemical & Drug injury

Injuries due to chemicals can be from therapeutic agents and nontherapeutic agents.

A. Adverse drug reactions 

Injuries due to therapeutic agents are known as adverse drug reactions. Adverse drug reactions are any response to a drug that is noxious and unintended and that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. ADRs are only rarely due to physician failures like inadequately monitored use or over use of drugs.

ADRs can be divided into two categories.

1.  Exaggeration of the intended pharmacologic effect which are largely predictable effects

2.  An unpredictable response unrelated to the drugs primary action.

The 1^st  one-encompasses all adverse reactions, which result from use of powerful drugs used to treat potentially fatal diseases like cancer.  For example use of large dose daunorubicin or doxorubicin to treat some forms of cancer may cause cardio toxicity. In the 2^nd   group the ADRs are unpredictable and they vary from individual to individual taking a specific drug.  The reactions is called idiosyncrasy and is due to an abnormal immunologic response to the drug or un predictable cytotoxicity caused by the drug.  Possible examples will be extensive hepatic  necrosis, which develops after intake of therapeutic dose of acetaminophen, or anaphylaxis, which develop after therapeutic dose of penicillin.

B. Non-therapeutic agents

 Ethyl alcohol

A large percentage of our population is a social drinker and still a significant number of individuals are alcoholic or alcohol dependent. Alcohol has an obvious acute effect but has also an effect of a long-standing use of alcohol on organs and tissues.

Alcohol Metabolism: -

About 2 to 10% of the ethanol consumed is excreted directly through the breath, urine or sweat.  The amount exhaled is directly proportional to the blood level and hence is used by metabolized by gastric mucosa alcohol dehydrogenase. The rest is rapidly absorbed from stomach & intestines, once in the liver alcohol is metabolized by three pathways in the liver cells. The 1^st  involves hepatic alcohol dehydrogenase, yielding acetaldehyde, which is then converted to acetate by aldehyde dehydrogenase . In this process NAD is converted to NADH. The 2^nd  involves the hepatic microsomal P-450 system. It too yields acetaldehyde, oxidisable to acetate. The 3^rd  pathway, which is less frequently utilized, involves peroxysomal catalase. All the three pathways yield acetaldehyde, which can be metabolized to acetate, and the 1^st  two produce more NADH from NAD.

Fig: Metabolism of alcohol:  the major (rate limiting) pathway is via ADH.

Acute Alcoholism

Acute alcoholism exerts its effects mainly on the CNS even though; the stomach and liver can also have reversible damages.  Alcohol has depressant effect on the CNS. It depresses the inhibitory control centers thereby releasing excitatory pathways that accounts for the wide spread belief that alcohol is a stimulant. The extent of CNS depression depends on the alcohol blood levels. The cortex affected first, the limbic system, cerebellum and finally brainstem are affected as the blood level increases.  Coma and total respiratory arrest become likely at 300 to 400 mg/dl levels. Not with a clearly understood mechanism, acute alcoholism has also "black out" effects that are episodes of forgetting what has happened during drinking.

Chronic alcoholism

The increase NADH:NAD ratio, which is created by alcohol metabolism, may be responsible for the metabolic consequences of chronic alcoholism. Chronic alcoholism produces morphologic changes in almost all organs and tissues.

Hepatic changes: these are the most common consequences of chronic alcoholism. These changes are namely fatty change, acute hepatitis and alcoholic cirrhosis.  These are discussed in adequate detail in the chapter that deals with liver diseases. Fatty changes can occur within a few days of even modest alcohol consumption. Cells are distended with fat accumulation, which can be mobilized when the exposure to alcohol is discontinued. Alcoholic hepatitis can occur with episodes of heavy drinking and may or may not be preceded by fat accumulation and may or may not be followed by cirrhosis which is the end stage of fatty changes that occur in chronic alcoholism.

Central nervous system changes

1-Wernicke’s encephalopathy

The commonest CNs change is wernicke’s encephalopathy.This is due to a thiamine deficiency that occurs during chronic alcoholism. The chronic alcoholic subsists with an inadequate dietary intake and alcohol itself impairs intestinal absorption of thiamine. This condition may occur in non-chronic alcoholics who become thiamine deficient for various reasons.

 Wernicke’s encephalopathy occur in a subset of alcoholics, probably in those who have an inherited or acquired abnormality of a thiamine dependent transketolase (enzyme involved in cerebral glucose & energy metabolism) reducing its affinity for thiamine.  Clinically it is characterized by ataxia, global confusion, ophtalmoplegia and often nystagmus. The underlying morphology includes  foci of symmetric discoloration and sometimes softening with congestion, & punctate hemorrhage in the paraventricular region of the thalamus & Hypothalamus, in the mammillary bodies about the aqueduct in the midbrain, in the floor of the fourth ventricle and in the anterior cerebellum.  The neurons may be relatively spared in the early stages  but eventually reveal degenerative changes and eventually cell death.

2- Korsakoff’s syndrome

After individuals, with Wernicke’s encephalopathy, are treated with thiamine, they show a profound memory loss, which does not improve with thiamine treatment.  This condition is termed as korsakoff’s syndrome.  There are no specific morphologic changes other than seen in wernicke’s encephalopiathy but this does not show any improvement with thiamine treatment. Hence it is believed that korsakoff’s syndrome is caused by direct neurotoxicity of ethanol compounded by a lack of thiamine. 

 3- Cerebellar ataxia

 Cerebellar degeneration, related to loss of purkinge’s cell in the cerebellar cortex, is a well-documented cerebellar change found in a minority of chronic alcoholics.  These are supposed to be due to thiamine deficiency as well, rather than ethanol direct toxicity.  Cortical atrophy is also a potential consequence but many studies didn’t reveal any reduction in size of the cortex in chronic alcoholics.

Peripheral Nerves 

The peripheral nerves suffer a demylinating  polyneuropathy, occasionally mononeuropathy that is fairly common in chronic alcoholics who are malnourished.  The basis is thought to be thiamine deficiency rather than ethanol toxicity.  

Cardiovascular system

A moderate intake of alcohol tends to increase the level of HDL and hence protects from atheroma formation and coronary heart disease. However heavy consumption, which causes liver cell injury, will decrease the level of HDL and contributes to atherosclerosis & coronary heart disease.  On the other hand a direct ethanol injury to myocardium will result in cardiomyopathy, which is discussed in the chapter that deals with heart diseases. 

Miscellaneous changes:

Chronic alcohol intake has a tendency to produce hypertension even though in low doses alcohol (ethanol) tends to reduce blood pressure. Chronic alcoholics suffer higher incidence of acute & chronic pancreatitis and regressive changes in skeletal muscle referred as alcoholic myopathy. During pregnancy a condition known as fetal alcohol syndrome may take place in infants whose mothers have been taking alcohol even as low as two to three drinks per day. The fetus can have microcephaly, mental retardation, facial mal formation & cardiac defects at times. Increased risks of cancer of pharynx, larynx, esophagus, stomach, & possibly rectum & lung have also been encountered in chronic alcoholics. 

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.

مواضيع ذات صلة

Bronchiectasis

Acute respiratory distress syndrome (ARDS)

وسائط الالتهاب الحاد

قرحة الاثني عشري Duodenal Ulcer

Small bowel infarction

أمراض الخلية

الالتهاب الرئوي الفصي (ذات الرئة الفصية) (Lobar Pneumonia)

النوبة القلبية ( Heart attack )

التهاب القصبات الهوائية ( Bronchitis )

قرحة المعدة ( Peptic ulcer)

الامراض المشتركة Zoonosis

Zellweger Syndrome