13.1 Environmental and Nutritional Diseases
Key Takeaways
- Lead inhibits ferrochelatase and ALA dehydratase, raising ALA and zinc protoporphyrin; the smear shows basophilic stippling and the neuropathy is wrist drop or foot drop.
- Asbestos pleural plaques are the most common manifestation; bronchogenic carcinoma is more common than mesothelioma, and tobacco multiplies lung-cancer risk but not mesothelioma risk.
- Ethanol oxidation floods hepatocytes with NADH, driving steatosis; Mallory-Denk bodies are phosphorylated cytokeratin 8/18; AST:ALT is typically greater than 2:1; Wernicke lesions sit in the mammillary bodies.
- Kwashiorkor is protein deficiency with edema and fatty liver from failed apolipoprotein export; marasmus is total-calorie wasting without that edema.
- Vitamin A deficiency causes night blindness and Bitot spots; vitamin A toxicity causes idiopathic intracranial hypertension. Folate deficiency megaloblastic anemia lacks the subacute combined degeneration that marks B12 deficiency.
Why environmental and nutritional disease is a scored Pathology topic
Pathology is 16% of NBCE Part I and is tested in Session 2 with Chemistry and Microbiology. Within that domain, environmental and nutritional diseases is 13%. The official page lists no sub-bullets. Do not skip the topic. The live exam still expects physical injury, chemical toxins, occupational exposures, smoking, alcohol, malnutrition, obesity, and vitamin deficiency or toxicity. Cellular injury chemistry (ATP collapse, ROS, membrane failure) lives in /study-guides/nbce-part1/pathology-mechanisms/fundamentals-pathology; coenzyme chemistry of the same vitamins lives in /study-guides/nbce-part1/chemistry-nucleic-energetics/vitamins-minerals. This section attaches the agent to the organ and the calling card.
Quick Answer: Name the toxin and the lesion (lead stippling and wrist drop; ferruginous body and mesothelioma; cherry-red CO and globus pallidus; Mallory-Denk and alcoholic hepatitis). Separate marasmus from kwashiorkor by edema and fatty liver. For every fat-soluble vitamin, know both deficiency and toxicity. B12, not folate, demyelinates the dorsal columns and corticospinal tracts.
Physical injury: heat, cold, electricity, radiation
Thermal burns are classified by depth. A first-degree burn is epidermis only (sunburn, painful, blanches). A second-degree (partial-thickness) burn enters dermis and blisters. A third-degree (full-thickness) burn destroys epidermis and dermis, including sensory endings, so the wound is painless, dry, and white or charred; it cannot re-epithelialize from adnexa and needs grafting. Rule-of-nines estimates adult surface: each arm 9%, each leg 18%, anterior trunk 18%, posterior trunk 18%, head 9%, perineum 1%. Shock after a large burn is hypovolemic from capillary leak plus evaporative loss. Curling ulcers are gastric stress ulcers after severe burns; Cushing ulcers follow intracranial injury (vagal acid).
Heat exhaustion is volume depletion with preserved thermoregulatory sweating. Heat stroke is failure of that regulation: core temperature typically above 40 °C, dry skin, rhabdomyolysis, DIC, and CNS dysfunction. Malignant hyperthermia is a different mechanism—ryanodine-receptor (RYR1) uncoupling in skeletal muscle after halogenated anesthetics or succinylcholine—not an environmental heat load.
Frostbite is ice-crystal injury plus thrombosis in distal digits and ears. Hypothermia slows metabolism, produces Osborn (J) waves, and predisposes to ventricular fibrillation during rewarming.
Electrical injury follows the neurovascular bundle. Low-voltage household current can tetanize muscle (the victim cannot let go) and trigger ventricular fibrillation. High-voltage current chars along bone, causes rhabdomyolysis and compartment syndrome, and may fracture bone by tetanic contraction. Lightning is a millisecond, high-voltage, often-survivable flashover with fern-like cutaneous Lichtenberg figures.
Ionizing radiation (X-rays, gamma, particles) ionizes water to hydroxyl radicals and produces double-strand DNA breaks. Lymphocytes and other rapidly cycling cells die first. Acute whole-body syndromes scale with dose: hematopoietic (pancytopenia, weeks), gastrointestinal (crypt death, days), and CNS (immediate, unsurvivable). Delayed effects are fibrosis (vascular endothelial injury) and neoplasia—leukemia, papillary thyroid carcinoma (especially in children), breast carcinoma, and osteosarcoma after radium. Ultraviolet B makes pyrimidine dimers; nucleotide-excision-repair failure is xeroderma pigmentosum (skin cancers in childhood). UV is the driver of basal-cell carcinoma, squamous-cell carcinoma, and melanoma. Non-ionizing radiation (microwave, radiofrequency) injures mainly by heat, not by DNA breaks.
Chemical injury: gases and metals
Carbon monoxide (CO) binds heme with about 200–250 times the affinity of oxygen, occupying the oxygen site and shifting the remaining oxyhemoglobin curve left (tighter binding, poorer tissue unloading). The classic viscera are cherry-red skin and blood and bilateral globus pallidus necrosis. Pulse oximetry misreads CO-Hb as oxy-Hb; co-oximetry is required. Cyanide inhibits cytochrome c oxidase (complex IV); cells cannot use delivered oxygen (histotoxic hypoxia). The teaching odor is bitter almond; lactic acidosis is severe. Contrast the two: CO blocks oxygen carriage and unloading; cyanide blocks oxygen use.
Carbon tetrachloride is converted by cytochrome P450 to a trichloromethyl radical → centrilobular hepatic necrosis and steatosis. Acetaminophen overdose saturates conjugation; NAPQI depletes glutathione and kills centrilobular hepatocytes—the same zone as CCl4, different chemistry.
| Metal | Source / occupation | High-yield lesions |
|---|---|---|
| Lead | Paint, batteries, pipes, ammunition, pottery glaze | Inhibits ferrochelatase and ALA dehydratase → ↑ ALA, ↑ zinc protoporphyrin, sideroblastic anemia, basophilic stippling (aggregated rRNA); abdominal colic; wrist drop / foot drop; Burton gingival lines; metaphyseal lead lines in children; encephalopathy and learning injury |
| Mercury | Vapor (hatters, gold extraction); methylmercury in fish (Minamata) | Elemental vapor: tremor, erethism (behavioral change), gingivitis. Organic: ataxia, visual-field constriction, fetal neurotoxicity. Inorganic salts: acute tubular necrosis |
| Arsenic | Groundwater, pesticides, smelting | Garlic breath, rice-water diarrhea, Mees lines, palmoplantar keratosis, raindrop pigmentation; cancers of skin, lung, bladder; also listed with hepatic angiosarcoma |
| Cadmium | Batteries, welding, electroplating | Chronic kidney injury, osteomalacia (Itai-itai), lung injury |
| Iron | Accidental pediatric overdose of tablets | Hemorrhagic gastritis, then hepatic necrosis; free-radical Fenton chemistry |
Lead items are the most frequently tested metal set: name both heme enzymes, the stippled smear, and the extensor neuropathy. Children absorb a larger fraction of ingested lead than adults; pica for paint chips is the classic pediatric stem.
Occupational dusts, fibers, and industrial carcinogens
Pneumoconioses are non-neoplastic lung reactions to inhaled inorganic dust. Particle size matters: 1–5 µm particles reach respiratory bronchioles and alveoli.
| Exposure | Occupation / source | Non-neoplastic lesion | Neoplastic / other hook |
|---|---|---|---|
| Asbestos (amphiboles such as crocidolite worse than chrysotile) | Shipyards, insulation, brakes, construction | Ferruginous bodies (iron-coated fibers); pleural plaques on parietal pleura (most common manifestation, not themselves cancer); interstitial fibrosis (asbestosis, lower lobes) | Bronchogenic carcinoma is more common than mesothelioma. Tobacco synergizes with asbestos for lung cancer, not for mesothelioma. Mesothelioma is calretinin-positive, encases the lung, long latency |
| Silica | Sandblasting, mining, foundry, stone cutting | Upper-lobe nodular fibrosis; eggshell hilar calcification; polarizable particles | Markedly increased tuberculosis risk; possible lung-cancer association |
| Coal | Mining | Anthracosis (harmless pigment) → coal-workers’ pneumoconiosis (upper-lobe macules) → progressive massive fibrosis | Caplan syndrome = rheumatoid nodules in coal (or silica) lung |
| Beryllium | Aerospace, electronics | Noncaseating granulomas that mimic sarcoid | Distinguish from sarcoid by occupational history |
| Cotton dust | Textiles | Byssinosis (Monday chest tightness) | Not a classic pneumoconiosis fibrosis story |
Industrial carcinogens to pair with a target organ (do not confuse with asbestos):
| Agent | Cancer |
|---|---|
| Benzene | Aplastic anemia and AML |
| Vinyl chloride (PVC manufacture) | Hepatic angiosarcoma |
| Aromatic amines (aniline, benzidine, 2-naphthylamine) | Urothelial (transitional) bladder carcinoma |
| Aflatoxin B1 (Aspergillus on stored grain/peanuts) | Hepatocellular carcinoma (p53 mutation), synergistic with HBV |
| Radon | Lung carcinoma (uranium miners, basements) |
| Hexavalent chromium, nickel, arsenic | Lung (and nasal for nickel) carcinoma |
| Thorium dioxide (Thorotrast) | Hepatic angiosarcoma |
| Nitrosamines | Gastric carcinoma |
Vinyl chloride → hepatic angiosarcoma is the cleanest one-to-one industrial pair after asbestos → mesothelioma. Arsenic and Thorotrast also appear on angiosarcoma lists; benzene is marrow, not liver.
Tobacco smoke
Cigarette smoke is a mixture of nicotine (addiction, sympathetic tone), polycyclic aromatic hydrocarbons and nitrosamines (mutagens), and oxidant gases. The high-yield pathology list is long because one exposure hits many organs:
- Lung: centriacinar emphysema, chronic bronchitis, squamous metaplasia of bronchi, squamous dysplasia, and bronchogenic carcinoma (squamous and small-cell especially tightly linked; adenocarcinoma still more common overall in many series and still increased in smokers).
- Vessels: atherosclerosis acceleration, abdominal aortic aneurysm, Buerger disease (thromboangiitis obliterans) in young male smokers.
- Head and neck and gut: laryngeal, oral, esophageal squamous carcinoma; pancreatic adenocarcinoma; peptic ulcer persistence.
- Urinary tract: urothelial carcinoma of bladder and renal pelvis.
- Perinatal: placental insufficiency, low birth weight, SIDS risk.
- Secondhand smoke still raises cardiovascular and lung-cancer risk; there is no safe threshold worth arguing on a Part I stem.
Smoking plus asbestos multiplies lung carcinoma risk (often taught as roughly multiplicative). Smoking does not multiply mesothelioma risk—mesothelioma is an asbestos story. That discriminator is more useful than memorizing a pack-year cutoff NBCE has never published.
Alcohol
Ethanol is oxidized by alcohol dehydrogenase (cytosol) to acetaldehyde, then by aldehyde dehydrogenase (mitochondria) to acetate. Both steps reduce NAD+ to NADH. Chronic intake also induces CYP2E1 (MEOS), which generates acetaldehyde and ROS. The NADH flood explains the metabolic face of a binge: DHAP is pushed toward glycerol-3-phosphate (triglyceride), oxaloacetate is pushed toward malate (TCA slows, hypoglycemia and ketoacidosis), and fatty-acid oxidation stalls. Acetaldehyde adducts damage microtubules and export of lipoprotein.
| Stage / lesion | Pathology |
|---|---|
| Hepatic steatosis | Reversible macrovesicular fat; begins centrilobular |
| Alcoholic hepatitis | Ballooning, neutrophils, Mallory-Denk bodies (phosphorylated cytokeratin 8/18), chicken-wire fibrosis |
| Cirrhosis | Micronodular → mixed nodules; portal hypertension and HCC risk |
| AST:ALT | Typically >2:1 (mitochondrial AST leak plus pyridoxine deficiency lowering ALT more) |
| Wernicke encephalopathy | Thiamine (B1) deficiency: confusion, ataxia, ophthalmoplegia; hemorrhage/necrosis of mammillary bodies and periaqueductal gray. Give thiamine before glucose |
| Korsakoff | Confabulation and inability to form new memories; often irreversible |
| Other organs | Dilated cardiomyopathy, acute and chronic pancreatitis, testicular atrophy, Folate deficiency megaloblastic change, fetal alcohol (smooth philtrum, microcephaly, septal defects), increased risk of squamous cancers of mouth, larynx, esophagus |
Do not confuse Mallory-Weiss (longitudinal mucosal tear at the GE junction after vomiting → hematemesis) with esophageal varices (portal hypertension, more often fatal) or Boerhaave (transmural esophageal rupture, mediastinitis). Mallory-Denk is a hepatocyte inclusion, not a mucosal tear.
Protein-calorie malnutrition and obesity
Marasmus is total energy deficiency: the child is wasted, head looks large, no edema, albumin near normal, and the body has consumed subcutaneous fat and then muscle. Kwashiorkor is protein deficiency with relatively maintained carbohydrate calories (weaning onto a starchy diet is the classic story). Failed hepatic apolipoprotein synthesis produces fatty liver. Low oncotic pressure plus a leaky, antioxidant-poor vasculature produces edema, ascites, and a swollen belly. Skin shows flaky-paint dermatosis; hair is pale and easily pulled. Immune failure in both states is real; kwashiorkor looks more ‘swollen well-fed’ and fools the unprepared examinee.
Cachexia of cancer and chronic infection is cytokine-driven (TNF-α / cachectin, IL-1, IL-6): appetite falls and muscle is proteolyzed even when calories are offered. It is not simply ‘not eating.’
Obesity is excess adipose, conventionally BMI ≥ 30 kg/m² (overweight 25–29.9). Adipocytes secrete leptin (should decrease appetite via the hypothalamus); most obese patients have high leptin and leptin resistance, not leptin deficiency. Adiponectin (insulin-sensitizing) falls. Free fatty acids, TNF, and IL-6 promote insulin resistance. Pathology that follows:
- Metabolic syndrome: central obesity, insulin resistance/diabetes, dyslipidemia, hypertension.
- Nonalcoholic fatty liver / NASH → cirrhosis, same histologic family as alcohol without the history.
- Obesity hypoventilation (Pickwickian) and obstructive sleep apnea: hypercapnia, pulmonary hypertension, right heart failure.
- Osteoarthritis of knees and hips (mechanical load plus inflammatory adipokines).
- Aromatization of androgens to estrogen in adipose → endometrial carcinoma and gallstones (cholesterol).
- Increased risk of hormone-sensitive and GI cancers, GERD, and surgical wound complications.
Chiropractic relevance is mechanical and inflammatory: knee and lumbar facet load rise with BMI, but the Part I item is still the endocrine and hepatic mechanism, not an adjustment plan.
Vitamin deficiency and toxicity
Fat-soluble vitamins (A, D, E, K) store in liver and fat, so deficiency is slow and toxicity is possible. Water-soluble vitamins (B complex, C) are not stored (B12 and folate in liver are the exceptions), so deficiency is faster and toxicity is uncommon except niacin flushing and B6 neuropathy.
| Vitamin | Deficiency disease | Toxicity / notes |
|---|---|---|
| A (retinol) | Night blindness, Bitot spots, xerophthalmia, keratinizing metaplasia of ducts and respiratory epithelium, immune failure | Idiopathic intracranial hypertension (pseudotumor cerebri), teratogen (isotretinoin), hepatotoxicity, bone resorption |
| D | Rickets (children: rachitic rosary, pigeon chest, metaphyseal cupping, bowing) and osteomalacia (adults: unmineralized osteoid, Looser zones) | Hypercalcemia, stones, metastatic calcification |
| E (tocopherol) | Hemolytic anemia (especially premature infants), spinocerebellar and dorsal-column neuropathy that can mimic Friedreich | Potentiates warfarin; bleeding |
| K | Factors II, VII, IX, X, proteins C and S; ↑ PT/INR; hemorrhagic disease of the newborn | Synthetic menadione can hemolyze in neonates; otherwise rare |
| B1 thiamine | Dry beriberi (neuropathy), wet beriberi (high-output heart failure), Wernicke-Korsakoff | — |
| B2 riboflavin | Cheilosis, corneal vascularization, magenta tongue | — |
| B3 niacin | Pellagra: diarrhea, dermatitis (Casal necklace), dementia, death. Also Hartnup and carcinoid (tryptophan diversion) | Flushing, hepatotoxicity at pharmacologic doses |
| B6 pyridoxine | Sideroblastic anemia, neuropathy, seizures in infants; precipitated by isoniazid | Sensory neuropathy at megadoses |
| B12 cobalamin | Megaloblastic anemia plus subacute combined degeneration (dorsal columns and corticospinal tracts); ↑ methylmalonic acid and homocysteine | Pernicious anemia, terminal-ileum Crohn or resection, Diphyllobothrium |
| Folate | Megaloblastic anemia, neural-tube defects; ↑ homocysteine without ↑ MMA; no SCD | Can mask B12 anemia if given alone |
| C ascorbic acid | Scurvy: failed hydroxylation of collagen proline/lysine → corkscrew hair, perifollicular hemorrhage, bleeding gums, poor wound healing, subperiosteal bleeds in children | Oxalate stones; rebound scurvy if stopped abruptly after megadoses |
| Biotin | Dermatitis, alopecia after raw-egg avidin or prolonged TPN | — |
Mineral hooks that travel with this topic: iodine deficiency → goiter and cretinism; zinc deficiency → acrodermatitis enteropathica, dysgeusia, poor wound healing; selenium deficiency → dilated cardiomyopathy (Keshan); copper deficiency (Menkes) versus copper overload (Wilson) is mostly a genetic item from the prior chapter.
A 4-year-old child with pica for peeling house paint has abdominal colic, a wrist-drop neuropathy, and a microcytic anemia. The smear shows basophilic stippling. Which paired enzyme inhibitions explain the heme-synthesis block?
A retired insulator has calcified parietal pleural plaques and a 40-pack-year smoking history. Which statement about cancer risk is accurate?
A weaned toddler has a swollen abdomen, pitting edema, and a fatty liver on imaging despite a starchy diet. Which nutritional diagnosis and mechanism fit?