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Topic 7

Part of the FMGE study roadmap. Botany topic pathol-007 of Botany.

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Environmental and Nutritional Pathology

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Environmental and Nutritional Pathology — Key Facts for FMGE Core concept: Environmental exposures and nutritional deficiencies cause significant systemic pathology High-yield point: Protein-energy malnutrition (marasmus vs kwashiorkor) and vitamin deficiencies are high-yield for FMGE ⚡ Exam tip: Recognize the pathology of smoking-related lung disease and alcohol-related liver disease

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Environmental and Nutritional Pathology — FMGE Study Guide

Protein-Energy Malnutrition

Marasmus

  • Cause: Severe caloric deficiency (inadequate overall energy intake)
  • Clinical features:
    • Severe wasting of muscle and subcutaneous fat
    • “Old man” appearance with prominent ribs
    • Normal appetite, alert behavior
    • No edema
    • Growth retardation
  • Laboratory: Low blood glucose, insulin, albumin; cortisol may be elevated
  • Age: Infants (especially 6-18 months) after weaning

Kwashiorkor

  • Cause: Predominant protein deficiency with some caloric intake
  • Clinical features:
    • Edema (pedal, then anasarca) - hallmark feature
    • Gross muscle wasting
    • Skin changes: flaky paint dermatosis, hypopigmentation
    • Hair changes: flag sign (alternating bands), sparse, easily pluckable
    • Hepatomegaly (fatty liver)
    • Apathy, irritability, anorexia
    • Failure to thrive
  • Laboratory: Very low albumin (<2.5 g/dL), low prealbumin
  • Age: Usually >18 months, after weaning, often after birth of sibling

Marasmic Kwashiorkor

  • Combined features of both: severe wasting + edema + low albumin

Pathophysiology

  • Starvation: Liver glycogen depleted within 24 hours → gluconeogenesis from amino acids → muscle breakdown
  • Protein deficiency: Decreased synthesis of albumin, transferrin, clotting factors
  • Edema mechanism: Low oncotic pressure (hypoalbuminemia) + electrolyte abnormalities + impaired water excretion

Vitamin Deficiencies

Fat-Soluble Vitamins

Vitamin A (Retinol) Deficiency:

  • Night blindness (nyctalopia) - earliest symptom
  • Xerophthalmia: Dry eyes, Bitot spots (keratinized conjunctival epithelium)
  • Keratomalacia: Corneal softening and ulceration → perforation → blindness
  • Skin changes: Follicular hyperkeratosis
  • Immune dysfunction: Increased susceptibility to infections
  • Sources: Liver, fish, dairy, eggs; β-carotene in vegetables

Vitamin D Deficiency:

  • Children: Rickets - craniotabes, rachitic rosary (costochondral junction enlargement), Harrison’s sulcus, pectus carinatum, bowed legs, growth retardation
  • Adults: Osteomalacia - bone pain, pseudofractures (Looser zones), muscle weakness
  • Causes: Decreased sun exposure, malabsorption, liver/kidney disease (1-alpha hydroxylation impaired), anticonvulsants
  • Sources: Sunlight (7-dehydrocholesterol → cholecalciferol), fatty fish, fortified milk

Vitamin K Deficiency:

  • Bleeding diathesis: Ecchymoses, GI bleeding, intracranial hemorrhage (newborns)
  • Laboratory: Elevated PT/INR (Factor II, VII, IX, X require vitamin K for carboxylation)
  • Causes: Newborns (sterile gut, no stores), warfarin, broad-spectrum antibiotics (kill gut flora), malabsorption, liver disease
  • Treatment: Phytonadione (vitamin K1)

Vitamin E Deficiency:

  • Rare, occurs with fat malabsorption, cystic fibrosis
  • Neurological: Spinocerebellar degeneration, ataxia, peripheral neuropathy
  • Hemolytic anemia (increased RBC fragility)
  • Neuromuscular: Muscle weakness, retinitis pigmentosa

Water-Soluble Vitamins

Vitamin B1 (Thiamine) Deficiency:

  • Beriberi:
    • Wet: High-output cardiac failure, peripheral edema, cardiomegaly
    • Dry: Peripheral neuropathy (symmetric, distal), muscle wasting
  • Wernicke-Korsakoff syndrome: Confusion, ataxia, ophthalmoplegia (Wernicke); confabulation, memory loss (Korsakoff)
  • Causes: Chronic alcoholism (most important), polished rice diets, hyperemesis gravidarum, dialysis
  • Tx: Thiamine replacement

Vitamin B2 (Riboflavin) Deficiency:

  • Ariboflavinosis: Cheilosis (angular stomatitis), glossitis (magenta tongue), seborrheic dermatitis, normocytic anemia
  • Causes: Alcoholism, malabsorption, burns

Vitamin B3 (Niacin) Deficiency:

  • Pellagra: Classic triad - Dermatitis (photosensitive rash in sun-exposed areas, Casal necklace), Diarrhea, Dementia
  • Causes: Alcoholism, Hartnup disease (tryptophan malabsorption), carcinoid syndrome
  • Tx: Niacin (nicotinic acid) supplementation

Vitamin B6 (Pyridoxine) Deficiency:

  • Peripheral neuropathy, sideroblastic anemia (impaired heme synthesis), seizures
  • Causes: INH (isoniazid) - forms inactive complexes with pyridoxine; alcoholism

Vitamin B12 (Cobalamin) Deficiency:

  • Causes: Pernicious anemia (autoimmune loss of intrinsic factor), gastrectomy, terminal ileum disease, strict vegan diet
  • Features:
    • Hematological: Megaloblastic anemia (macrocytic RBCs, hypersegmented neutrophils, low reticulocyte count)
    • Neurological: Subacute combined degeneration (posterior columns → loss of proprioception, sensory ataxia; lateral corticospinal tracts → weakness); peripheral neuropathy
    • Glossitis (beefy red tongue)
  • Schilling test: Detects cause of B12 malabsorption
  • Tx: Hydroxocobalamin IM

Folic Acid Deficiency:

  • Megaloblastic anemia (no neurological features unlike B12)
  • Causes: Alcoholism, malnutrition, pregnancy, anticonvulsants, celiac disease
  • Neural tube defects: Spina bifida, anencephaly - supplementation prevents this

Vitamin C (Ascorbic Acid) Deficiency:

  • Scurvy:
    • Gum swelling/bleeding (gingivitis), loose teeth
    • Perifollicular hemorrhages and petechiae
    • Subperiosteal hemorrhage (especially in children - painful limbs)
    • Poor wound healing, corkscrew hairs
    • Spoon-shaped nails (koilonychia)
  • Causes: Elderly, alcoholics, “tea and toast” diet
  • Function: Collagen synthesis (hydroxylation of proline and lysine), antioxidant, enhances iron absorption

Acute Intoxication

  • CNS depression, disinhibition, ataxia, nystagmus
  • Lethal dose: blood alcohol >400 mg/dL (respiratory depression)

Chronic Alcoholism

Alcoholic Liver Disease:

  • Fatty liver (Steatosis): Reversible, swollen hepatocytes with fat vacuoles
  • Alcoholic hepatitis: Hepatocyte necrosis, Mallory bodies (intracytoplasmic eosinophilic inclusions), neutrophilic infiltrate, ballooning degeneration
  • Alcoholic cirrhosis: Micronodular cirrhosis, Hobnail appearance, decreased liver size

Mechanism: Ethanol metabolism → NADH excess → inhibits fatty acid oxidation → fat accumulation; acetaldehyde is toxic

Other effects:

  • Wernicke-Korsakoff (thiamine deficiency)
  • Peripheral neuropathy
  • Cardiomyopathy (dilated)
  • Fetal Alcohol Syndrome: Growth restriction, facial abnormalities (short palpebral fissures, smooth philtrum, thin upper lip), CNS abnormalities
  • Cerebellar atrophy
  • Pancreatitis

Pulmonary Effects

  • Chronic bronchitis: Hypertrophy of mucus-secreting glands, goblet cell hyperplasia, productive cough
  • Emphysema: Destruction of alveolar walls, loss of elasticity; centriacinar (smoking) vs panacinar (α1-antitrypsin deficiency)
  • COPD: Combination of chronic bronchitis and emphysema
  • Lung cancer: Squamous cell carcinoma and small cell carcinoma most strongly associated with smoking
  • Chronic inflammation: Recurrent infections, cough, dyspnea

Other Effects

  • Cardiovascular: Atherosclerosis, coronary artery disease, peripheral vascular disease
  • Cancers: Larynx, oropharynx, esophagus, bladder, kidney, pancreas
  • Peripheral vascular disease: Buerger’s disease (thromboangiitis obliterans) - strongly associated with smoking
  • Peptic ulcer disease

Heavy Metal Toxicity

Lead (Pb):

  • Sources: Paint, pottery, gasoline (historically), occupational
  • Children: Intellectual disability, developmental delay, microcephaly, behavioral problems
  • Adults: Motor neuropathy (wrist drop - radial nerve), anemia (microcytic, basophilic stippling), colic (abdominal pain), gingival lead line
  • Lab: Elevated blood lead, free erythrocyte protoporphyrin

Mercury:

  • Sources: Fish, dental amalgams, industry
  • Acute: GI symptoms, neurological (tremor, ataxia, paresthesias)
  • Minamata disease: Methylmercury poisoning from contaminated fish

Arsenic:

  • Sources: Pesticides, well water
  • Garlic odor breath, vomiting,rice-water stool, QT prolongation
  • Chronic: Hyperpigmentation, hyperkeratosis, Mees lines (nails), cancer (skin, lung)

Radiation Injury

Ionizing Radiation

  • Acute: Nausea, vomiting, bone marrow suppression (lymphocytes most sensitive)
  • Delayed: Fibrosis, cancer (leukemia - AML within 5-7 years, solid tumors later)
  • Skin: Erythema, desquamation, ulceration

Ultraviolet Radiation

  • Acute: Sunburn (erythema, pain, peeling)
  • Chronic: Photoaging, skin cancer (BCC, SCC, melanoma)
  • DNA damage: Pyrimidine dimers → mutations → skin cancer

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