ENVIRONMENTAL AND LIFESTYLE RELATED PATHOLOGY II

Question 1

Define adverse reactions of therapeutic drugs

Answer 1

Adverse reactions of therapeutic drugs refer to untoward effect of drugs given in conventional therapeutic settings.

Question 2

Which therapies commonly have adverse effects?

Answer 2

Anticoagulants
Menopausal hormone therapy
Oral Contraceptives
Anabolic steroids.
Acetaminophen
Aspirin (acetylsalicylic acid)

Question 2

Medical use and adverse effects of ANTICOAGULANTS:
-Warfarin (a vit. K antagonist)
-Dabigatran ( a thrombin inhibitor)?

Answer 2

Medical Use: Anticoagulation
Adverse effects: Thrombosis (at subtherapeutic level)
Bleeding

Question 3

Medical use and adverse effects of Menopausal hormone therapy (Hormone replacement therapy)?

Answer 3

Medical Use: For alleviation of menopausal symptoms(e.g., hot flushes) and reduction of incidence of fractures(presumably by reducing osteoporosis.

Why? Estrogen Decline: During menopause, estrogen levels significantly decline. Estrogen plays a crucial role in maintaining bone density by inhibiting bone resorption (the process where bone is broken down

Adverse effects: Prolong therapy increases the risk of breast cancer and thromboembolism.

Unopposed estrogen have an increased risk of endometrial and breast carcinoma

Question 4

Medical use and adverse effects of Oral contraceptives (contain estradiol and variable amounts of progestin, or progestin alone)?

Answer 4

Medical Use: Contraception: Prevent ovulation and/or implantation

Adverse effects:
Increased risk of DVT and thromboembolism in smokers
Decreased risk of ovarian and endometrial cancer.
Increased risk of cervical cancer in women infected with HPV.
Hepatic adenoma (typically, HCAs are solitary and are found in young women in association with use of estrogen-containing medications)

Question 5

Medical use and adverse effects of Anabolic steroids (synthetic version of testosterone)?

Answer 5

Medical Use: Athletic performance enhancement

Adverse effects: Testicular atrophy
Gynecomastia
Stunted growth in adolescents.
Virilization (a condition in which a female develops characteristics associated with male hormones (androgens) e.g. beard hair) and menstrual dysfunction in females.
Psychiatric changes, premature MI, hepatic cholestasis

Question 5

Medical use and adverse effects of Acetaminophen?

Answer 5

Medical Use: Analgesic (pain-relieving)

Adverse effects: Acute liver failure.
Active metabolite in the liver depletes glutathione stores.
Treatment of overdose: N-acetylcysteine

Question 6

Medical use and adverse effects of Aspirin (Acetylsalicylic acid)?

Answer 6

Medical Use: Analgesic
Adverse effects: Overdose initially causes respiratory alkalosis, followed by potentially fatal metabolic acidosis.
Salicylate toxicity (Salicylism) manifests as headache, dizziness, tinnitius, difficulty in hearing, mental confusion, drowsiness, nausea, vomiting, and diarrhea.

Chronic toxicity manifests as:
Acute erosive gastritis and upper GI bleeding
Bleeding tendency due to reduced platelet aggregation.
Long term use of aspirin with phenacetin is associated with renal papillary necrosis (analgesic nephropathy)

Can cause Reye’s syndrome in children

Question 7

What are the commonly abused drugs?

Answer 7

Common drug of abuse include cocaine, opiates (including heroin, oxycodone, methadone, morphine e.t.c), amphetamines and related drugs, marijuana, ecstasy, phencyclidine, ketamine, LSD, e.t.c.

Question 8

What is the Class, molecular target, symptoms and adverse effects of cocaine?

Answer 8

Class: Psychomotor stimulants.
Others include: amphetamines, MDMA (ecstasy)

Molecular target: Dopamine transporter (antagonist) & Serotonin receptors (toxicity)

Symptoms: Euphoria, and stimulation.
No physical dependence (no physical withdrawal symptoms)
Profound psychological withdrawal

Adverse Effects: Seizures
Cardiac arrhythmias and sudden death, hypertension and stroke.
In pregnancy: fetal hypoxia, neurologic deficits, spontaneous abortions.
Chronic use:
-Perforation of the nasal septum
- Dilated cardiomyopathy

Question 9

What is the Class, molecular target, symptoms and adverse effects of Heroin, Oxycodone, Methadone, Meperidine?

Answer 9

Class: Opiod narcotics (opiates)

Molecular target: Mu opiod receptor (agonist)

Symptoms: Euphoria, hallucination, somnolence, and sedation.
Physically addictive.

Adverse Effects: Sudden death (from overdose leading to cardiopulmonary arrest/respiratory depression, pulmonary edema, and/or arrhythmia).
Infections: skin abscesses and cellulitis, bacterial endocarditis (S. aureus), Increased risk of contracting HIV and hepatitis viruses.
Pulmonary pathology: foreign body granuloma in the lungs, pulmonary abscesses, pulmonary edema.
Focal glomerulosclerosis
Amyloidosis.
Treatment: naloxone

Question 9

What is the Class, molecular target, symptoms and adverse effects of Amphetamine and related drugs. Methamphetamine (speed),
3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”)?

Answer 9

Class: Psychomotor stimulants.

Molecular target: Induces CNS dopamine release and thus slows glutamate release.
MDMA enhances CNS serotonin release.

Symptoms: Euphoria. Long term use can lead to violent behaviour, confusion, paranoia, and hallucination.

Adverse Effects: Loss of appetite, weight loss, dry mouth, stomach upset/pain, nausea/vomiting, dizziness, headache, diarrhea, fever, nervousness, difficulty sleeping

Question 10

What is the Class, molecular target, symptoms and adverse effects of Marijuana (found in the hemp plant – Cannabis sativa)?

Answer 10

Class: Cannabinoids.
Others include Hashish

Molecular target: CBI cannabinoid receptor (agonist).
Acute substance is tetrahydrocannabinol (THC) – modulates the hypothalamic-pituitary-adrenal axis

Symptoms: Bloodshot eyes,
Increased appetite, lack of motivation, weight gain, nervous or paranoid behaviour, impaired coordination, slowed reaction time, dry mouth, dizziness, memory impairement, euphoria.

Adverse Effects: Acute THC use distorts sensory perception and impairs motor coordination, increases heart rate and blood pressure.
Smoking marijuana is associated with bronchitis, pharyngitis, and chronic pulmonary diseases.
THC may have therapeutic benefits in treating chemotherapy-induced nausea and chronic pain syndromes

Question 12

What are Injuries that can occur by physical agents?

Answer 12

Mechanical trauma,
Thermal injury (including thermal burns, hyperthermia, and hypothermia)
Electrical injury
Injury produced by ionizing radiation

Question 13

Discuss MECHANICAL TRAUMA
What are the patterns of injury?

Answer 13

Mechanical forces can injure soft tissue, bones, or head.

Outcomes depend on the shape of the colliding object, force imparted and tissue that bear the brunt of impact.

All soft tissue react similarly to mechanical forces, and the pattern of injury can be divided into:
abrasions
contusions
laceration
incised wounds and puncture wounds.

Forensic pathology uses morphologic analyses of wound, molecular methods for identity testing, and sophisticated methods to detect the presence of foreign substances.

Question 13

Discuss THERMAL BURNS

Answer 13

Burn injury and smoke inhalation can cause shock, sepsis, and respiratory insufficiency, all of which are life threatening.

The clinical significance of burns depends on:
- the depth of the burn (superficial, partial or full-thickness).
-the percentage of body surface involved (>20% of surface area can lead to shock, infection).
- internal injuries from inhalation of hot and toxic fumes.
-promptness and efficacy of postburn therapy.

Question 14

Discuss HYPERTHERMIA

Answer 14

HYPERTHERMIA:
Prolonged exposure to elevated ambient temperature can result in the following:
-Heat cramps(cramps of voluntary muscles) occur from loss of electrolytes through sweating.
-Heat exhaustion: results from a failure of the CVS to compensate for hypovolemia, 2o water depletion. Onset is sudden with prostration and collapse.
-Heat stroke: associated with high ambient temperatures, high humidity and exertion. Thermoregulatory mechanism fail, sweating ceases, and core body temperature markedly elevates (up to 400 C). Here, there is generalized peripheral vasodilation, with decreased effective circulating blood volume. Necrosis of muscles and myocardium can occur with systemic effects, like arrhythmias and DIC.

Question 15

Discuss HYPOTHERMIA

Answer 15

HYPOTHERMIA:
This occurs with prolonged exposure to low ambient temperature.
At a core temperature of 900 F, one loses consciousness; with further cooling, bradycardia and atrial fibrillation occur.
Direct injury to cells and tissue can occur through crystallization of intracellular and extracellular water.
Indirect injury: Slowly falling temperature may induce vasoconstriction and increased vascular permeability, leading to edematous change (e.g. trench foot)
Persistent low temperature can cause ischemic injury.

Question 16

Discuss electrical injury

Answer 16

Passage of electrical current through the body depending on the current strength, duration, and path, tissue resistance may cause:
-no effect
-sudden death by disruption of neural regulatory impulses or cardiac condition pathways
- thermal injury

Question 17

Discuss INJURY PRODUCED BY IONIZING RADIATION

Answer 17

Radiation has a wide range of energies spanning the electromagnetic spectrum vis:
- Nonionizing radiation includes UV and infrared light, radiowaves, microwaves, and soundwaves.
-Ionizing radiation includes x-rays and gamma rays, high-energy neutrons, alpha particles, and beta particles.

Question 18

What is the Main determinant of biological effect of ionizing radiation?

Answer 18

Main determinant of biological effect of ionizing radiation include:
Rate of delivery
Field size
Cell proliferation
Oxygen effects and hypoxia
Vascular damage

Question 19

What is INJURY PRODUCED BY IONIZING RADIATION?

Answer 19

The acute effects of ionizing radiation range from overt necrosis at high doses (>10 Gy), killing of proliferating cells at intermediate doses (1 to 2 Gy), to no histopathologic effect (at ≤0.5Gy).
Apoptosis occurs when cells undergo extensive DNA damage or if they are unable to repair this damage.
Surviving cells may show delayed effects of radiation injury: mutations, chromosomal aberrations and genetic instability.

Fibrosis can occur in the radiation field weeks or months after exposure.
This occurs primarily as a consequence of replacement of dead tissue by scar, vascular injury, destruction of tissue stem cells, and the release of inflammatory cytokines that promote fibroblast activation and matrix synthesis.

Question 20

What is DNA DAMAGE AND CARCINOGENESIS?

Answer 20

DNA damage from radiation includes single-base damage, single and double-strand breaks (DSBs), and DNA-protein cross-links.

DSBs are more serious and mutations, including deletions, inversions, and translocations, can occur during repair

In the absence of cell cycle checkpoint controls, such mutations may initiate carcinogenesis.

Question 21

Effects

Question 22

What are the morphologic consequences of radiation injury?

Question 23

What should an adequate diet provide?

Answer 23

An adequate diet should provide:–
* Sufficient energy in the form of carbohydrates, fats andproteins.
* Vitamins and minerals, which function as co-enzymes or hormones in vital metabolic pathways or, as for the case of Ca &P, as important structural components.

Question 24

What is malnutrition and what is a malnourished child?

Answer 24

The World Health Organization defines malnutrition as
“the cellular imbalance between supply of nutrients and
energy and the body’s demand for them to ensure growth, maintenance, and specific functions.“
BMI <16kg/m2 is considered malnutrion.
A child whose weight fall to less than 80% of normal is considered to be malnourished.

Question 26

What are the MAIN NUTRITIONAL DISORDERS?

Answer 26

MAIN NUTRITIONAL DISORDERS
Obesity
Kwashiorkor
Marasmus
Anorexia nervosa
Bulimia nervosa
Vitamin deficiency
Trace element deficiency

Question 27

What are the primary and secondary causes of malnutrition?

Answer 27

Primary: related to diet.
Secondary: related to:
–Nutrient malabsorption.
–Impaired nutrient utilization or storage.
–Excess nutrient losses.
–Increased need for nutrients.

Question 28

Discuss PEM

Answer 28

PEM is characterised by inadequate dietary intake of protein and calories (or malabsorption) with resultant muscle, fat, and weight loss, lethargy and generalised weakness.
Kwashiokor - protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty change).
Clinical picture is small child with swollen belly
Marasmus – protein-calorie malnutrition resulting in tissue wasting.

Question 29

What is Anorexia Nervosa?

Answer 29

Anorexia nervosa is self-induced starvation.
It has the highest death rate of any psychiatric disorder
Clinical finding are similar in severe PEM
Severe weight loss, amenorrhea, anemia, and electrolyte disturbance.
Decreased thyroid hormone production causes cold intolerance, bradycardia, constipation, dry scaly skin, and hair thinning
Decreased bone density is associated with low estrogen levels
Sudden death due to arrhythmias in the setting of hypokalemia.

Question 30

What is Bulimia nervosa?

Answer 30

Bulimia is characterized by food binging followed by self-induced vomiting; diuretic or laxative abuse may also occur

More common than anorexia nervosa

Better overall prognosis

Body weight and hormonal level are normal.
Medical complications include hypokalemia (can cause arrhythmias), aspiration of gastric contents , esophageal or gastric laceration, parotitis, enamel erosion, increased amylase and esophageal varices.