MOD Exam 4 Active Recall

What do you know about toxicology?

• Definition: Study of poisons/toxic agents

• Distribution: Where does the poison go? (blood → organs → storage or excretion)

  • Distribution = Where does it go?

• Effects: What damage does it cause? (cellular injury → tissue injury → organ dysfunction)

  • Effects = What damage does it cause?

• Mechanism: How does it cause damage? (metabolism/Phase I & II → detoxification or activation → toxic metabolites/ROS → injury)

  • Mechanism = How does it cause that damage?

• Also includes: Physical agents (radiation, heat)

Define xenobiotic

A foreign (external) chemical introduced into the body that must be metabolized. It may be detoxified or activated into a more toxic metabolite.

What do you know about the toxicology mechanism pathway?

Xenobiotic

↓

Phase I (Cytochrome P450 - heme enzyme in liver’s smooth ER)

↓

Detoxification OR Bioactivation

↓

Primary metabolite

↓

Phase II (More water-soluble)

• Glucuronidation

• Sulfation

• Glutathione conjugation

• Methylation

↓

Highly water-soluble metabolite

↓

Excretion

What do you know about CO poisoning?

• Exposure: Garage, furnace, house fire, smoke inhalation

• Mechanism: 200× affinity for hemoglobin → carboxyhemoglobin → ↓ O₂ delivery → hypoxia

• Clinical clue: Cherry-red skin/blood, headache, confusion, unconsciousness

• Pathology: Basal ganglia (globus pallidus/lenticular nucleus) ischemic injury

• Laboratory finding: ↑ Carboxyhemoglobin

• Acute: High concentration, first exposure

• Chronic: Low concentration, repeated exposure over time → delayed neurologic sequelae

• Exam trap: Appears well oxygenated but is actually hypoxic; CO does not destroy RBCs.

What do you know about outdoor air pollution?

Agency: EPA

Purpose: Monitor air quality & set safe exposure standards

High-risk patients:

• Asthma

• COPD

• Cardiovascular disease

Major effects:

• Lung inflammation

• Exacerbation of respiratory disease

• Increased cardiovascular risk

Criteria air pollutants:

• CO

• NO₂

• SO₂

• O₃

• Lead

• Particulate matter (PM ≤10 µm)

What do you know about indoor air pollution?

Cause: Poor ventilation in tightly insulated homes “Button up”

Major pollutant: Radon

Source: Radioactive gas from soil/rock beneath homes

Entry: Foundation cracks, basement floors, crawl spaces

Health effect:

• Lung cancer

High-yield fact:

• Smoking = #1 cause of lung cancer

• Radon = #2 overall

  • #1 cause in nonsmokers

Other pollutant:

• Tobacco smoke (#1 ca cause)

• formaldehyde (Building material/factor → irritant → Human carcinogen)

• Wood smoke (

• Bioaerosols (Mites/Dander → Allergies & asthma)

• Polycyclic aromatic hydrocarbons (PAHs)

What do you know about lead poisoning?

Source

• Old Houses (paint)

• Paint chips

• Dust

• Soil

• Old plumbing

High-risk patient

• Children (↑ GI absorption)

Mechanism

• Inhibits heme synthesis

Blood

• Microcytic hypochromic anemia

• Basophilic stippling (classic blood smear finding)

  • small blue granules inside red blood cells

Health effects

• Developmental delay

• Cognitive impairment

• Abdominal pain/constipation (lead colic)

• Peripheral neuropathy (adults)

Treatment

• Chelation

  • EDTA

  • Succimer

Children = CNS effects vs. Adults = peripheral neuropathy.

What do you know about mercury posioning?

Source

• Organic (methylmercury) → fish/seafood (especially large predatory fish)

• Inorganic → industrial compounds

• Elemental → industrial exposure

Mechanism

• Binds sulfhydryl (-SH) groups on proteins

• Results in protein dysfunction and cell injury

Major Target Organs

• 🧠 CNS

• 🫘 Kidneys

Health Effects

Adults

• Headache

• Memory loss

Children

• Encephalopathy

• Mental deterioration

Kidneys

• Renal injury

High-Yield Fact

• Methylmercury crosses the placenta and the blood-brain barrier

• Developing fetal brain is especially susceptible

• Minamata = Mercury

What do you know about arsenic poisoning?

Source

• Soil

• Groundwater

• Wood preservatives

• Herbicides

• Mining/smelting

Mechanism

• Interferes with mitochondrial oxidative phosphorylation

• ↓ ATP production

Major Target Organs

• GI tract

• Nervous system

• Cardiovascular system

• Skin

Acute Effects

• GI toxicity

• CNS toxicity

• Cardiovascular toxicity

Chronic Effects

Skin

• Hyperpigmentation

• Hyperkeratosis

Nervous system

• Sensorimotor neuropathy

• Paresthesias

• Numbness

Cardiovascular

• Hypertension

• Prolonged QT

• Ventricular arrhythmias

igh-Yield Fact

Long-term exposure → increased risk of:

• Skin cancer

• Lung cancer

• Bladder cancer

Whst do you know about cadmium poisoning?

Source

Nickel-cadmium batteries

Source

• Nickel-cadmium batteries

• Mining

• Electroplating

• Fertilizers

• Food

• Contaminated soil

Mechanism

• Not emphasized

• (May involve ROS production)

Major Target Organs

• 🫁 Lungs

• 🫘 Kidneys

• 🦴 Bone

Lung Effects

• Obstructive lung disease

Kidney Effects

• Renal tubular damage

• End-stage renal disease

Bone Effects

• Calcium loss

• Osteoporosis

• Osteomalacia

High-Yield Disease

Itai-Itai disease

• Cadmium

• Osteoporosis

• Osteomalacia

• Renal disease

Cancer

• Lung cancer

What do you know about occupational health risks?

Organic Solvents

• CNS depression

• Liver toxicity

• Kidney toxicity

• Benzene → Leukemia

• Vinyl chloride (PVC) → Hepatic angiosarcoma

• Silica → Silicosis

• Asbestos → Mesothelioma (and asbestosis)

• Coal dust → Coal workers' pneumoconiosis

• Beryllium → Chronic berylliosis

What do you know about Smoking?

High-Yield Fact

• Most prevalent/preventable cause of death →

Lung

• Emphysema

• Chronic bronchitis

• COPD

Cardiovascular

• Atherosclerosis

• Myocardial infarction

Pregnancy

• Preterm birth

• IUGR

• Spontaneous abortion

Cancer

• Lung (classic)

• Esophagus

• Pancreas

• Bladder

• Kidney

• Cervix

• Bone marrow

Nicotine

• Addictive component

• Other smoke chemicals = toxic/carcinogenic

Risk

• Increases with pack-years

What do you know about alcohol poisoning?

• Alcohol is metabolized primarily in the liver.

• Ethanol → Alcohol dehydrogenase → Acetaldehyde (Toxic metabolite) → aldehyde dehydrogenase → Acetic acid

• Acetaldehyde is the toxic metabolite

• Acetaldehyde causes cellular injury and contributes to carcinogenesis.

• Acute = fatty liver, poor coordination, impaired judgement

• Chronic alcohol use can cause thiamine (B₁) deficiency leading to

  • Wernicke encephalopathy (acute) - COA

    • Confusion

    • Ophthalmoplegia

    • Ataxia

  • Korsakoff syndrome (chronic) - MAC

    • Memory loss

    • Amnesia

    • Confabulation (makeup-stories)

What do you know about therapeutic drugs?

1. Warfarin

   • Vitamin K antagonist

   • Atrial fibrillation

   • Prevents stroke

   • Bleeding

2. Menopausal Hormone Therapy

   1. Treats menopausal symptoms

   2. Increased DVT risk

3. Anabolic Steroids

   1. Performance enhancement

   2. Acne

   3. Gynecomastia

   4. Testicular atrophy

   5. Facial hair (women)

   6. Menstrual changes

   7. Psychiatric effects

   8. Myocardial infarction

   9. Stunted growth

4. Oral Contraceptives (Robbins)

   1. Increased thromboembolism risk

   2. Risk is even higher in women with Factor V Leiden

   3. Hepatic adenoma (benign)

What do you know about acetaminophen?

1. Most common OTC analgesic

2. Found in many medications

   • Tylenol

   • OTC meds

   • Cold meds

3. Accidental overdose is common because multiple medications may contain it

4. Can cause severe liver injury

5. Can progress to acute liver failure

What do you know about aspirin?

1. Accidental ingestion in children / overdose in adults.

2. Early respiratory alkalosis → later mixed metabolic acidosis + respiratory alkalosis.

3. Tinnitus (classic clue) = ringing in the ears.

4. Acute erosive gastritis → bleeding.

5. Reye syndrome = aspirin + child + viral illness → encephalopathy, heoatomegaly

6. Treatment = Sodium Bicarbonate (NaHCO₃)

What do you know about cocaine?

Blocks reuptake of Norepinephrine & Dopamine → Increases Sympathetic activity → Vasoconstriction, Hypertension, Tachycardia

• Source: coca plant

• Major complications

  • Myocardial infarction

  • Cardiac arrhythmias

  • Stroke

  • Sudden death

• Treatment: benzodiazepines

• Restless, hunger, severe depression, sleep disturbances withdrawals

What do you know about opiates?

• CNS depression →Respiratory depression → Respiratory arrest → Death

• Treatment: Naloxone (Narcan)

• Source: poppy plant

What do you know about heroine?

• Heroin → CNS depression → Respiratory depression → Respiratory arrest → Death

• IV heroin use

  • Skin → Abscesses, cellulitis

  • Heart → Infective endocarditis

  • Emboli → Septic emboli

  • Lung → Lung abscess

  • Kidney → Amyloidosis, FSGS

What do you know about methamphetamine?

• Speed or meth

• Powerful CNS stimulant → Large catecholamine release → Hypertension & Tachycardia

• Major complications

  • Arrhythmias

  • Stroke

  • Sudden death

• euphoric feeling → crash

• Long term: hallucinations & paranoia

what do you know about MDMA (Ecstasy)?

• Massive serotonin release → CNS stimulation → Euphoria

• May lead to

  • Hyperthermia

  • Dehydration

  • Neurologic complications

• Life threatening effects

  • hypertension

  • tachycardia

  • hyponatremia

What do you know about marijuana?

• Psychoactive compound THC → CNS effects → Euphoria and relaxation → Acute (4 - 5 hours) → Continued use: continued Cognitive impairment, Psychomotor impairment, Poor judgment of time, Poor judgment of speed, Poor judgment of distance

• Cardiovascular effects

  • Increased heart rate

  • Increased blood pressure

  • Angina (especially in CAD patients)

• Neurologic effect

  • sensory perception

  • motor coordination

• Symptoms:

  • Euphoria

  • Anxiety

  • Paranoid delusions

  • Perception of slowed time

  • Impaired judgment

  • Increased appetitie

  • Dru mouth

  • Hallucinations

• 3x more tar inhaled and retained than a tobacco cigarette

  • Can lead to:

    • Laryngitis

    • Pharyngitis

    • Bronchitis

    • Cough/hoarseness

    • Asthma-like symptoms

What do you know about amphetamines?

Amphetamines → Stimulant → Hypertension + tachycardia → Stroke / arrhythmias / sudden death

What do you know about inhalants such as paint?

Paint/Glue Huffing → Rapid onset → Rapid resolution → Disinhibition, euphoria, slurred speech, disturbed gait, disorientation, drowsiness → Peri-nasal/oral rash (repeated use)

What do you know about bath salts?

Bath Salts → Amphetamine-like chemicals → 4-methyl-methcathinone + MDPV

What are the major patterns of aspirin, acetaminophen, cocaine, heroine, MDMA, marijuana, inhalants and bath salts?

• Aspirin → tinnitus, respiratory alkalosis → mixed acidosis, Reye syndrome

• Acetaminophen → acute liver failure

• Cocaine → NE/dopamine reuptake blockade

• Heroin → respiratory depression + IV drug complications

• MDMA → serotonin release

• Marijuana → THC, acute/chronic effects

• Inhalants → rapid onset/resolution + peri-nasal/oral rash

• Bath salts → amphetamine-like stimulants

What do you know about burns?

• Burn Severity → Determined by: Depth of burn % and Total body surface area (TBSA) involved → Outcome depends on: Prompt therapy, Fluid & electrolyte management and Prevention/control of wound infection

• Superficial → Confined to epidermis

• Full-thickness 3rd-degree burn → White or charred → Dry → Painless → Destruction of nerve endings

• Partial-thickness 2nd-degree burn → Pink or mottled → Blisters → Painful → Appearance depends on burn depth

• Burned tissue Histology → Coagulative necrosis (devitalized tissue) → Adjacent viable tissue → Inflammatory cells accumulate → Marked exudation

• Inhalation burns (Mouth, nose, upper airways) → airway & lung injury → develops within 24-48 hours

What do you know about hyperthermia?

• Prolonged exposure to elevated ambient temperatures → Leads to: Heat cramps, Heat exhaustion, Heat stroke

• Heat stroke → Hyperkalemia → Cardiac effects (Tachycardia, arrhythmias, other systemic effects) → sustained skeletal muscle contraction → rhabdomyolysis (muscle necrosis) → exacerbates hyperthermia

What do you know about hypothermia?

Prolonged exposure to low ambient temperatures → Two mechanisms

1. Direct Injury

   • Cold exposure → Physical disruption within cells → High salt concentrations → Crystallization of intra- & extracellular water → Cell injury

2. Indirect Injury

   • Cold exposure → Circulatory changes → Slow chilling → Vasoconstriction & Increased Vascular permeability → Edema → Hypoxia → Trench foot → Slowed blood flow and Vessel constriction → Ischemia

Clinical Recognition

Core temperature ≈ 90°F → Loss of consciousness → Further temperature decrease → Bradycardia → Atrial fibrillation

What do you know about Marasmus?

• Severe deficiency of both protein and calories

• Loss of muscle and body fat → emaciation

• Relative preservation of serum albumin

• Somatic protein compartment primarily affected

What do you know about Kwashiorkor?

• Protein deficiency with relatively adequate calories

• Hypoalbuminemia

• Generalized edema

• Fatty liver

• Skin changes ("flaky paint")

• Visceral protein compartment primarily affected

What do you know about Anorexia nervosa?

Self-induced starvation → Marked weight loss → Amenorrhea (diagnostic feature) → Low thyroid hormone effects, Cold intolerance, Bradycardia, Constipation → Bone density ↓ (osteoporosis risk)

What do you know about Bulimia?

Binge eating → Self-induced vomiting → Generally better prognosis than anorexia

What do you know about vitamin D?

Know the pathway:

• Skin → 7-dehydrocholesterol, decreased UVB, Vitamin D3 (cholecalciferol) → Liver → ⭐ 25-hydroxycholecalciferol (25-OH-D) Inactive → Kidney → 1,25-dihydroxyvitamin D

Function

• Vitamin D → Inc Calcium absorption, Inc Phosphorus absorption → Bone mineralization → Maintains serum calcium

Deficiency

• Children → Rickets

• Adults → Osteomalacia → decrease Calcium → (Hypocalcemic tetany—possible but uncommon because PTH usually compensates)

What do you know about vitamin A?

Vision → Night blindness → Xerophthalmia → Blindness, Maintains epithelium → Squamous metaplasia, Immune function → increased Infections

What do you know about vitamin C?

Collagen synthesis → Collagen cross-linking → Scurvy

What do you know about vitamin E?

Antioxidant → Spinocerebellar degeneration → Hemolytic anemia

What do you know about vitamin K?

Activates clotting factors → Bleeding

What do you know about Ghrelin?

Stomach → Hunger hormone → increase Food intake → Weight gain

What do you know about Leptin?

Adipose tissue → Satiety hormone → decrease Food intake → Energy balance

What do you know about obesity and cancer?

• Obesity → Chronic inflammation → Increases Insulin / Increases IGF-1, Increases Estrogen production, Decreases Adiponectin → Increased cancer risk

  • Insulin / Increases IGF-1 → cell proliferation

  • Estrogen production → stimulate cell growth

  • Adiponectin → Less suppression of cell proliferation

  • Chronic inflammation → promotes carcinogenesis