6.2 about 26 minDeep Learning viewL6 p.12–13L1 p.12–15

Toxins, metals and venom

Gases, metals and toxic alcohols each hit one molecular target. Name the target and the labs follow: hemoglobin binding for CO, cytochrome oxidase for cyanide, heme enzymes for lead, and ADH-made acids for the toxic alcohols.

Air pollutants

L6 p.12

The lecture groups the common outdoor and indoor pollutants. Most injure the airway directly; the exceptions, which act on hemoglobin or mitochondria, get their own topics below.

Air pollutantsL6 p.12

  • Sulfur dioxide

    Source
    Smog, combustion
    Effect
    Burning in nose and throat, dyspnea, asthma attacks

  • Ozone (ground-level)

    Source
    NOₓ + hydrocarbons + UV light
    Effect
    Free radicals injure respiratory epithelium, inflame the upper airway, worsen asthma

  • Nitrogen dioxide

    Source
    Combustion, smog
    Effect
    Damages cilia, irritates airway mucosa

  • Particulate matter (soot, <10 µm)

    Source
    Industrial and vehicle exhaust
    Effect
    Reaches alveoli, is phagocytosed by macrophages, releases inflammatory mediators

Carbon monoxide and cyanide: two ways to starve a mitochondrion

L6 p.12–13L1 p.12–15

Both come from fires and both cause lactic acidosis, but they fail at different points on oxygen's path. Carbon monoxide binds hemoglobin's iron, forming carboxyhemoglobin: oxygen is not carried or released (and the curve shifts left), so delivery falls. Cyanide binds the ferric iron of cytochrome c oxidase (complex IV): oxygen is delivered normally but cannot be used.

Telling them apartL1 p.12–15

  • Target

    Carbon monoxide
    Hemoglobin (carboxyhemoglobin)
    Cyanide
    Cytochrome c oxidase (complex IV)

  • PaO₂

    Carbon monoxide
    Normal
    Cyanide
    Normal

  • SaO₂ by co-oximetry

    Carbon monoxide
    Low (COHb measured)
    Cyanide
    Normal

  • Venous oxygen

    Carbon monoxide
    Low (less delivered)
    Cyanide
    High (delivered but not extracted)

  • Classic clue

    Carbon monoxide
    Cherry-red (often postmortem); headache first; globus pallidus injury
    Cyanide
    Bitter-almond breath (unreliable); very rapid collapse

  • Both

    Carbon monoxide
    Lactic acidosis; brain and heart fail first
    Cyanide
    Lactic acidosis; brain and heart fail first

A standard pulse oximeter is misleading in CO poisoning (it cannot separate COHb from oxyhemoglobin). Co-oximetry measures the real fractions.

Lead and other heavy metals

L6 p.12–13

Lead is the exam favorite because it blocks two enzymes of heme synthesis, δ-aminolevulinic acid dehydratase (ALA dehydratase) and ferrochelatase. Heme falls, its precursors rise, and the stalled ferrochelatase step traps iron and degrades ribosomal RNA in red cells, producing basophilic stippling. The result is a microcytic (or sideroblastic) anemia.

Lead on heme synthesis

  1. Lead
  2. Inhibits ALA dehydratase and ferrochelatase
  3. Heme ↓; protoporphyrin and ALA ↑; iron trapped
  4. Basophilic stippling, microcytic/sideroblastic anemia
L6 p.12

Heavy metals and their targetsL6 p.12–13

  • Lead

    Source
    Old paint, batteries, metal casting, pipes
    Findings
    Basophilic stippling; nephrotoxicity (proximal tubule); in children, encephalopathy and gingival/metaphyseal lead lines; wrist/foot drop; abdominal colic

  • Mercury

    Source
    Fish (methylmercury)
    Findings
    Constricted visual fields, peripheral neuropathy, tremor, nephrotoxicity, hypertension, diaphoresis

  • Arsenic

    Source
    Pesticides, contaminated groundwater, vineyards
    Findings
    Inhibits lipoic-acid-dependent enzymes (pyruvate dehydrogenase) → lactic acidosis; diarrhea, garlic breath; Mees lines on nails; skin/lung/liver cancer

Lead lines (gums, long-bone metaphyses) and arsenic Mees lines (transverse white nail bands) are both named after the exposure that causes them; do not confuse them.

Methanol and ethylene glycol: the gaps that name them

L6 p.13

Methanol and ethylene glycol are harmless until ADH oxidizes them to toxic acids. Early on, the unchanged parent alcohol raises the osmolal gap (extra osmotically active molecules the standard calculation misses). As ADH converts them to acids, a raised anion-gap metabolic acidosis develops and the osmolal gap closes.

Toxic alcoholsL6 p.13

  • Methanol

    Source
    Windshield washer fluid, moonshine
    ADH product
    Formic acid
    Signature
    Blindness (optic nerve), anion-gap acidosis

  • Ethylene glycol

    Source
    Antifreeze
    ADH product
    Glycolic then oxalic acid
    Signature
    Calcium oxalate crystals, acute kidney injury, hypocalcemia with tetany

  • Isopropyl alcohol

    Source
    Rubbing alcohol
    ADH product
    Acetone
    Signature
    Fruity breath, deep coma; raises the osmolal gap but not the anion gap (no acid end-product)

Worked calculation · Reading the ethylene glycol case (Sim. Q31)

Na⁺
137 mEq/L
Cl⁻
99 mEq/L
HCO₃⁻
8 mEq/L
Measured − calculated osmolality
32 mOsm/kg

Formula

Anion gap = Na⁺ − (Cl⁻ + HCO₃⁻)

Midterm sim. p.12–13

Solvents, pesticides and venom

L6 p.12–13

The rest of the lecture's listL6 p.12–13

  • Benzene

    Source
    Solvent, chemical industry
    Effect
    Bone marrow toxicity: aplastic anemia, acute leukemia

  • Asbestos

    Source
    Insulation, shipyards
    Effect
    Lung cancer and mesothelioma (latent decades)

  • Polyvinyl chloride

    Source
    Plastics industry
    Effect
    Hepatic angiosarcoma

  • Organophosphates

    Source
    Pesticides
    Effect
    Inhibit acetylcholinesterase → cholinergic crisis (SLUDGE: salivation, lacrimation, urination, defecation, GI cramps, emesis), miosis, bradycardia, fasciculations; ↓ RBC cholinesterase

  • Black widow venom (latrotoxin)

    Source
    Latrodectus bite
    Effect
    Opens Ca²⁺ channels to release acetylcholine and norepinephrine → severe muscle cramps and rigidity mimicking an acute abdomen

Exposure-to-mechanism case lab

L6 p.12–13

This is the chapter's centerpiece. Each case gives an exposure; you pick the agent, its molecular target and the key lab or image, then one more clue is revealed and you decide whether it changes your answer. It covers the fire victim, the garage, the battery factory, the alcoholic, the acetaminophen overdose and the antifreeze case from this chapter.

Centerpiece · Exposure-to-mechanism case lab

Exposure to mechanism

For each exposure or deficiency, choose the agent, then its molecular target, then the key finding. One more clue is then revealed: decide whether it changes your interpretation.

A firefighter is pulled unconscious from a burning house. He has soot in his airway and a severe lactic acidosis. His arterial PaO₂ is normal.

1 · Agent

Which exposure clue decides the agent?

Decisive exposure clue

2 · Target

You first suspect carbon monoxide. What is its molecular target?

Enzyme, cofactor or metabolite

3 · Finding

Which lab finding fits carbon monoxide?

Key lab or image

Knowledge check · 6.2

Answer, read why, and try again whenever you like. Answers are kept in both study modes.

0 of 4 correct
  1. Q1Cyanide vs CO: venous oxygenL6 p.13L1 p.15

    A firefighter is pulled from a house fire. He is comatose with a severe lactic acidosis. His arterial PaO₂ is normal and a venous sample drawn from a central line looks unusually bright red.

    Which mechanism best explains the arterialized venous blood?

  2. Q2Ethylene glycol: anion and osmolal gapsMidterm sim. p.12–13L6 p.13

    A man is found collapsed next to a vomit pool. He is confused with arm and jaw muscle spasms. Na⁺ 137, Cl⁻ 99, HCO₃⁻ 8; the osmolal gap is 32 mOsm/kg and urinalysis shows oxalate crystals.

    What has he most likely ingested, and why the spasms?

  3. Q3Lead and heme synthesisL6 p.12

    A 4-year-old who lives in an old house is irritable and anemic. The blood film shows microcytic red cells with coarse blue granules.

    Which pair of enzymes is inhibited?

  4. Q4Occupational carcinogensL6 p.13

    A worker in a plastics plant develops a malignant vascular tumor of the liver. Which exposure fits?

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