Injury by therapeutic agents ( adverse drug reactions (ADRs)). Definition: Any response to a drug which is noxious and unintended that occur at doses used in humans for prophylaxis ,diagnosis and therapy.
Exogenous estrogen : used for postmenopausal women to slow the adverse effects of osteoporosis complications : * Endometrial carcinoma, which is increase 3-6 times after 5 years. * Breast carcinoma, there is a small increased risk of breast carcinoma with the use of estrogens. * Cardiovascular diseases. * Venous thrombosis. * Cholestasis. .
Oral contraceptive : These have the following adverse effects: Some increased risk of cervical carcinoma Increased risk of thromboembolism Increase in the incidence of hypertension Well-defined relation to hepatic adenoma. Increase incidence of gall bladder disease.
Antineoplastic drugs : 1- Bone marrow suppression. 2- Immunosuppression. 3- carcinogenic. Antibiotics : 1- Hypersensitivity reaction. 2- Bacterial resistance. 3- Eradication of normal flora
Acetaminophen (Paracetamol): This drug causes liver cell necrosis, particularly those surrounding the central vein of the lobule (centrilobular liver cell necrosis). The toxic dose is 15-25 gram. Clinically toxicity begins with nausea, vomiting, diarrhea and later jaundice and eventually liver failure. Acetylsalicylic acid (Aspirin): Acutely: at first repiratory alkalosis develop, which is followed by metabolic acidosis. The toxic dose for children is 2 gram, and for adult 10-30 gram. Chronic toxicity occurs in patient with chronic inflammatory conditions such as rheumatoid arthritis who used to take regularly large doses of aspirin as analgesia to their joint pain. These patients take an average of 3 grams or more daily or for long periods. Chronic toxicity is manifested by headache, dizziness, tinnitus, mental confusion, nausea, vomiting, diarrhea, acute erosive gastritis and GIT bleeding.
Alcohol-Metabolism and Health Effects Acute alcohol abuse causes drowsiness at blood levels of approximately 200 mg/dL. Stupor and coma develop at higher levels. Alcohol is oxidized to acetaldehyde in the liver by alcohol dehydrogenase, by the cytochrome P-450 system, and by catalase.
Acetaldehyde is converted to acetate in mitochondria and utilized in the respiratory chain. Alcohol oxidation by alcohol dehydrogenase depletes NAD, leading to accumulation of fat in the liver and metabolic acidosis. The main effects of chronic alcohol consumption are fatty liver, alcoholic hepatitis, and cirrhosis, which causes portal hypertension and increases the risk of development of hepatocellular carcinoma.
Chronic alcohol consumption can cause bleeding from gastritis and gastric ulcers, peripheral neuropathy associated with thiamine deficiency, and alcoholic cardiomyopathy, and increases the risk for acute and chronic pancreatitis. Chronic alcohol consumption is a major risk factor for cancers of the oral cavity, pharynx, larynx, and esophagus. The risk is greatly increased by concurrent smoking.
Lead Mercury Arsenic
Lead poisoningMost commonly associated with toxic effects in humans .Children absorb more ingested lead than adults, The main source of exposure for children is lead containing paints. Excess lead causes CNS defects in children &peripheral neuropathy in adults. It competes with calcium in bones & interferes with remodeling of cartilage .It also cause anemia.
The major source is contaminated fish. The developing brain is highly sensitive to methyl mercury which accumulate in the brain & blocks ion channels. High level of mercury may cause cerebral palsy, deafness & blindness
It is naturally found in soil & water .It is a component of some wood preservatives. Excess arsenic interferes with mitochondrial oxidative phosphorylation & cause toxic effects in GIT, CNS & CVS.
1.Mechanical Trauma 2.Thermal injury 3.Electrical injury 4.Radiation injury
Type of injury depends on the: Type of object. Amount of the energy discharged at the moment of the impact. Tissues or organs bearing the impact. The patterns of injury can be in the form of: Abrasion is a wound produced by scraping or rubbing resulting in removal of the superficial layer (epidermis) of Skin. Contusion (bruise) : is a wound produced by a blunt object & characterized by damaged to blood vessels & extravasations of blood into tissues.Laceration : is a tear of tissue by a blunt object leading to a wound with irregular edges. Incised wound caused by a sharp instrument Puncture wound which is caused by a long narrow instrument & its termed (penetrating) Gun shot wounds are special forms of puncture wounds. One of the most common causes of mechanical injury is car accidents causing head injury, chest & knee injury .Chest injury include sternal & ribs fractures & less commonly lacerations of the spleen & liver.
1.Burns 2.Hyperthermia 3.Hypothermia
A full thickness burn involved destruction of epidermis & dermis with loss of dermal appendages .Both 3rd & 4th degree burns are in this category. Grossly the burns are white & anesthetic . In partial thickness burn, the deeper portions of the dermis are spared which include the first & second degree (both epidermis & superficial dermis). The partial thickness burns are pink with blister & painful .
Microscopic features: Devitalized tissue shows coagulative necrosis. Adjacent vital tissue develops inflammatory changes with inflammatory cells and exudation. In burns involving more than 20% of the body surface there will be a shift of body fluids into the interstitial compartment at the burn site. This systemically results in hypovolemic shock. There is also increase susceptibility to infection, especially with Pseudomonas AEROGIONSA, Staph. And Candida. This is due to: Loss of skin as a mechanical barrier Impairment of immunity, both cellular & humoral. Impairment in lymphocyte & macrophage function.
Hyperthermia : heat cramps: refer to cramps of voluntary muscles due to loss of electrolytes via sweating. Heat exhaustion : result from failure of CVS to compensate for hypovolaemia secondary to water depletion. Heat stroke: Is associated with high temp. & high humidity with a failure of thermoregulatory mechanism , sweating ceases with a rise in body temp. The underlying mechanism is generalized peripheral vasodilatation with decreased blood volume. The ultimate effects are necrosis of the muscles including myocardium, Arrhythmia & DIC
In cold weather and when body temperature falls below 32c, there is loss of consciousness occurs, followed by bradycardia and atrial fibrillation. In slowly developing drop of surrounding temp. Vasoconstriction Increase vascular permeability These lead to local edema & subsequent atrophy and fibrosis. In sudden and sharp drop in surrounding temp. 1. Vasoconstriction 2. Increase viscosity of blood These lead to ischemia & later on to degenerative changes in peripheral nerves
Electrical injuries, which may result in death, can arise from low-voltage currents (i.e., in the home and workplace) or from high-voltage currents from high-power lines or lightning. Injuries are of two types: (1) burns and (2) ventricular fibrillation or cardiac and respiratory center failure, resulting from disruption of normal electrical impulses. The type of injury and the severity and extent of burning depend on the amperage and path of the electric current within the body.
Ionizing radiationThe various forms of ionizing radiation X-ray,α,β & γ rays can all induce cancer in animals and man, they injure the cells through which they pass with formation of ionized molecules highly reactive with nucleic acids proteins, thus cancer develop many years after the first exposure, so the effect of repeated doses are cumulative
The carcinogenic effect of ionizing radiation and UV is due to damage to the DNA mainly, this includes : 1- changes in single bases ( point mutation) and consequent change of an amino acid in protein products of affected gene. 2- breaks in one or both strands of double helix (DNA) produce fragments which are liable to re-unite in the wrong order and this results in transfer of sequences of various lengths sometime visible microscopically as translocations and other chromosomal abnormalities
The effect of ionizing radiation on different tissues depend on the type of radiation and on the nature of tissue irradiated. Bone tissue absorbs and scatters ionizing radiation more than soft tissue because of its density, and as a consequence hemopoeitic tissue is severely damaged, thus leukemia are among the commoner type of cancer resulting from ionizing radiation
Any dividing cell that acquired mutations has the potential to become carcerous. Radiation in very large doses kills the cells & therefore is not associated with occurrence of tumor
Ultraviolet(UV) radiation In contrast to ionizing radiation UV penetrates tissue poorly and its effects are limited to the exposed skin and the main source of exposure is sun Carcinoma of the skin, like basal cell carcinoma ,squamous cell carcinoma, & melanoma occur in light skinned people The dark skinned races are protected due to absorption of UV rays by melanin In xeroderma pigmentosa which is a rare precancerous inherited condition in which there is a defect of a repair enzyme which excise abnormal DNA segments