End-of-Year paper 2 General systemic OmpathStudy

General and Systemic Pathology SAQ — 2024/2025 A short-answer and long-answer pathology paper. The original source pages carry no printed answer key, so the model answers below are written to match standard MBChB pathology teaching, not copied from the source. Section A — Short-answer questions 1. Give an outline of the various congenital neural tube defects, mentioning their distinguishing features. Model answer: Neural tube defects arise from failure of neural tube closure around day 26-28 of gestation; folate deficiency is a major risk factor. Anencephaly: absence of the cranial vault and cerebral hemispheres; incompatible with life. Spina bifida occulta: incomplete fusion of vertebral arches, skin-covered, often asymptomatic (may show a tuft of hair or dimple). Meningocele: herniation of meninges (CSF-filled sac) through the vertebral defect, cord not involved. Myelomeningocele: herniation of both meninges and neural tissue; the most severe and common clinically significant form, associated with motor/sensory deficits and hydrocephalus. Encephalocele: herniation of brain tissue and meninges through a cranial defect. 2. Classify chemical carcinogenic agents, giving examples and the types of cancers caused. Model answer: Direct-acting agents: act without metabolic conversion, e.g. alkylating agents (cyclophosphamide) - associated with leukaemia. Indirect-acting (procarcinogens): require metabolic activation (usually by cytochrome P450) - polycyclic aromatic hydrocarbons in tobacco smoke (lung cancer), aflatoxin B1 (hepatocellular carcinoma), aromatic amines (bladder cancer), nitrosamines (gastric/oesophageal cancer). Inorganic/physical chemical agents: asbestos (mesothelioma, bronchogenic carcinoma), vinyl chloride (hepatic angiosarcoma), arsenic (skin and lung cancer). Hormones: unopposed oestrogen (endometrial carcinoma). Tumour promoters: agents that are not carcinogenic alone but enhance the effect of an initiator, e.g. phorbol esters. 3. Compare and contrast autosomal dominant and autosomal recessive disorders, focusing on their mode of transmission and the manifestation of their clinical features. Model answer: Autosomal dominant: one mutant allele is sufficient to cause disease; affects both sexes equally; transmitted vertically (every generation typically has an affected member); each child of an affected parent has a 50% risk; shows variable expressivity and incomplete penetrance; usually involves structural proteins or receptors (e.g. Huntington disease, Marfan syndrome). Autosomal recessive: both alleles must be mutant for disease to manifest; carriers (heterozygotes) are clinically normal; transmission is horizontal (affects siblings, often skips generations); consanguinity increases risk; usually involves enzyme defects; tends to be more uniform in severity and often presents earlier in life (e.g. cystic fibrosis, sickle cell disease). 4. Discuss the different pathophysiological categories of oedema, giving two examples for each. Model answer: Increased hydrostatic pressure: congestive heart failure, deep venous thrombosis/venous obstruction. Reduced plasma oncotic pressure (hypoalbuminaemia): nephrotic syndrome, liver cirrhosis/protein-losing enteropathy. Lymphatic obstruction: filariasis, post-mastectomy lymphoedema (or tumour infiltration of lymphatics). Sodium and water retention: acute renal failure, heart failure (secondary hyperaldosteronism). Increased vascular permeability: acute inflammation, anaphylaxis/allergic reactions. 5. Describe the immune mechanisms of glomerular injury. Model answer: In-situ immune complex formation: antibodies bind directly to fixed glomerular antigens, e.g. anti-GBM antibody disease (Goodpasture syndrome). Circulating immune complex deposition: antigen-antibody complexes formed elsewhere deposit in the glomerulus and activate complement, e.g. post-streptococcal glomerulonephritis, lupus nephritis. Cell-mediated immunity: T-cell dysfunction leading to a circulating permeability factor with foot-process effacement but no immune deposits, e.g. minimal change disease. Alternative complement pathway activation: e.g. membranoproliferative glomerulonephritis type II (dense deposit disease). Cytotoxic antibody-mediated injury and neutrophil/complement-mediated damage to the glomerular basement membrane in several of the above. 6. Give an outline of the major risk factors for atherosclerosis. Model answer: Major/modifiable: hyperlipidaemia (raised LDL), hypertension, cigarette smoking, diabetes mellitus. Major/non-modifiable: increasing age, male sex, family history/genetic predisposition. Additional/minor risk factors: obesity, physical inactivity, chronic stress, hyperhomocysteinaemia, C-reactive protein elevation, chronic inflammatory states. 7. Discuss the aetiology, pathogenesis and morphology of liver cirrhosis. Model answer: Aetiology: chronic alcohol use, chronic viral hepatitis (B, C), non-alcoholic fatty liver disease, autoimmune hepatitis, biliary disea