Tobacco, alcohol and drugs

Tobacco smoke is the leading preventable cause of death worldwide, and the lecture lists its key constituents: nicotine, polycyclic aromatic hydrocarbons (tar), phenol, nitrosamines, carbon monoxide and nitrogen oxides. They are worth separating, because each explains a different disease.

The lecture's body map adds myocardial infarction and systemic atherosclerosis, peptic ulcer, and cancers of the pancreas and bladder. Stopping smoking lowers the risk of cardiovascular disease and of lung, mouth, larynx, esophagus, pancreas, kidney and bladder cancer. Secondhand smoke harms children most: respiratory and middle-ear infections and worse asthma.

The liver oxidizes ethanol in two steps. Alcohol dehydrogenase (ADH) in the cytosol converts ethanol to acetaldehyde, and acetaldehyde dehydrogenase (ALDH) in the mitochondria converts acetaldehyde to acetate, which becomes acetyl-CoA. Both steps use NAD⁺ and release NADH. That shared cofactor is the bottleneck behind the metabolic findings in the next topic.

The lecture's organ map shows where chronic use injures: liver (steatosis, alcoholic hepatitis, cirrhosis), pancreas (acute and chronic pancreatitis), stomach (acute gastritis), heart (dilated cardiomyopathy), nervous system (Wernicke and Korsakoff syndromes from thiamine deficiency, neuropathy), testis (atrophy), bone (osteoporosis, aseptic necrosis) and blood (anemia, poorer resistance to infection).

Dehydrogenases are reversible, and the NADH/NAD⁺ ratio decides which way they run. When ethanol oxidation floods the hepatocyte with NADH, every reaction that uses NADH speeds up and every reaction that needs NAD⁺ slows down. Read the lab findings as consequences of that one shift.

The lecture's table pairs each drug with its signature toxicity. Match the pupils and the vital signs to the drug.

The lecture's body diagram organizes the examination by system: pupil size, respiratory rate, blood pressure, heart rate and body temperature, plus cerebellar or extrapyramidal signs, cyanosis, needle tracks and abdominal tenderness. Read the pattern as a whole rather than one sign: large pupils with a fast pulse point to a stimulant, small pupils with slow breathing to an opioid or sedative, and fast breathing with tinnitus to salicylate (L6 p.11).

At therapeutic doses most acetaminophen is conjugated (glucuronide, sulfate) and excreted; only a small fraction is oxidized by CYP2E1 to the reactive metabolite NAPQI, which glutathione neutralizes. In overdose the conjugation pathways saturate, more acetaminophen is pushed through CYP2E1, and NAPQI consumes glutathione. Once glutathione is depleted, NAPQI binds cellular proteins and drives oxidative injury.

Salicylate (aspirin) overdose gives tinnitus and vertigo, confusion, and a mixed acid–base disturbance: salicylate stimulates the respiratory center directly (a primary respiratory alkalosis) and uncouples oxidative phosphorylation and blocks the TCA cycle (a primary raised anion-gap metabolic acidosis). Adults classically show both at once.

Oral contraceptives act mainly through estrogen. It raises hepatic synthesis of clotting factors I (fibrinogen), V and VIII, a hypercoagulable state that increases venous thromboembolism; it raises angiotensinogen, which can cause hypertension; it lowers jejunal folate absorption, a minor contributor to macrocytic anemia; and it is associated with benign hepatic adenoma, a well-demarcated liver tumor that can bleed.

Before the explanation, predict which pathway each lab finding comes from. The activity gives one case of chronic alcohol use and asks you to route each finding back to the reaction the high NADH/NAD⁺ ratio favors.