BDS General Pathology Flashcards

24 sample cards from the General Pathology deck

Sampled from the end of the deck, so these are different cards from the ones shown on the syllabus page.

1. Give the classic example and molecular defect of an autosomal dominant structural-protein disorder.

   Marfan syndrome — an autosomal dominant disorder caused by mutation in the FBN1 gene encoding fibrillin-1, weakening connective tissue and causing skeletal (tall, arachnodactyly), ocular (lens dislocation), and cardiovascular (aortic aneurysm/dissection) features.

2. Contrast the inheritance pattern of X-linked recessive disorders in males versus females.

   X-linked recessive disorders (e.g., hemophilia A, Duchenne muscular dystrophy) affect hemizygous males fully; heterozygous females are usually asymptomatic carriers. There is no male-to-male transmission, and all daughters of an affected male are obligate carriers.

3. State the karyotype and key features of Down syndrome, and its most common cause.

   Trisomy 21, karyotype $47,XY,+21$ (or $47,XX,+21$). Most cases (~95%) arise from meiotic nondisjunction, strongly correlated with advanced maternal age. Features: intellectual disability, flat facies, epicanthic folds, single palmar crease, congenital heart defects, and increased leukemia/Alzheimer risk.

4. Give the karyotypes and distinguishing features of Klinefelter and Turner syndromes.

   Klinefelter: $47,XXY$ — hypogonadal male, tall, gynecomastia, small testes, infertility. Turner: $45,X$ — phenotypic female, short stature, webbed neck, streak (fibrous) ovaries with primary amenorrhea, and coarctation of the aorta.

5. Define a multifactorial (polygenic) disorder and list its characteristics.

   A disorder caused by the combined action of multiple genes and environmental factors, producing a continuous (quantitative) trait. Examples: hypertension, diabetes mellitus, cleft lip/palate, neural tube defects. Recurrence risk rises with number of affected relatives and severity, and does not follow simple Mendelian ratios.

6. What are the three main mechanisms by which point mutations affect protein function?

   (1) Missense mutation — single amino-acid substitution (e.g., sickle cell: $\text{Glu} \to \text{Val}$ at position 6 of $\beta$-globin); (2) Nonsense mutation — creates a premature stop codon and truncated protein; (3) Silent mutation — no amino-acid change. Frameshifts from insertions/deletions also disrupt the reading frame.

7. Explain trinucleotide repeat expansion as a molecular basis of genetic disease, with one example.

   Amplification of a specific 3-nucleotide sequence beyond a normal threshold destabilizes gene function, often worsening in successive generations (anticipation). Example: Fragile X syndrome from $\ce{CGG}$ repeat expansion in FMR1; Huntington disease from $\ce{CAG}$ repeats in HTT.

8. Define anticipation and genomic imprinting in the context of genetic disease.

   Anticipation: a disease appears at an earlier age and/or with increasing severity in successive generations (typical of trinucleotide-repeat disorders). Genomic imprinting: differential expression of a gene depending on parental origin, e.g., Prader-Willi (paternal deletion) versus Angelman (maternal deletion) of chromosome 15q.

9. Define neoplasia and distinguish the parenchyma from the stroma of a tumor.

   Neoplasia is a new, abnormal, uncoordinated, and autonomous proliferation of cells that persists after the initiating stimulus ceases. Parenchyma = the proliferating neoplastic cells (determines the tumor's name/behavior); stroma = the supporting connective tissue and blood vessels (host-derived).

10. Give the general nomenclature rules for benign and malignant tumors of epithelial and mesenchymal origin.

    Benign: add '-oma' to the cell of origin (e.g., adenoma, lipoma, chondroma). Malignant mesenchymal tumors: '-sarcoma' (e.g., osteosarcoma, liposarcoma). Malignant epithelial tumors: 'carcinoma' (e.g., adenocarcinoma, squamous cell carcinoma).

11. Compare benign and malignant tumors on differentiation, growth rate, invasion, and metastasis.

    Benign: well differentiated, slow growth, expansile/encapsulated (no invasion), and no metastasis. Malignant: variable/poor differentiation (anaplasia), rapid growth with atypical mitoses, invasive infiltrative margins, and capacity to metastasize.

12. Define anaplasia and list its key cytologic features.

    Anaplasia is lack of differentiation, the hallmark of malignancy. Features: pleomorphism (variation in cell/nuclear size and shape), hyperchromatic nuclei with a high nuclear:cytoplasmic ratio (approaching $1{:}1$), prominent nucleoli, abundant and atypical mitoses, and loss of normal polarity/architecture.

13. List the three principal routes by which malignant tumors metastasize.

    (1) Lymphatic spread (typical of carcinomas, to regional lymph nodes), (2) hematogenous spread (typical of sarcomas, via veins to liver and lungs), and (3) seeding of body cavities/surfaces (transcoelomic, e.g., peritoneal spread of ovarian carcinoma).

14. Name the sequential steps of the metastatic cascade.

    (1) Detachment (loss of E-cadherin/cell adhesion), (2) invasion of ECM/basement membrane (via proteases like matrix metalloproteinases), (3) intravasation into vessels, (4) survival and transport in circulation, (5) extravasation, and (6) colonization/growth at the distant site with angiogenesis.

15. State the classic two-step chemical carcinogenesis model of initiation and promotion.

    Initiation: irreversible, mutation-causing DNA damage by a carcinogen (initiator). Promotion: reversible, non-mutagenic stimulation of proliferation of initiated cells by a promoter. Tumors arise only when initiation is followed by promotion; promotion alone or promotion before initiation does not cause tumors.

16. List the four classes of normal regulatory genes whose damage drives carcinogenesis.

    (1) Proto-oncogenes (growth-promoting; gain-of-function → oncogenes), (2) tumor suppressor genes (growth-inhibiting; loss-of-function), (3) apoptosis-regulating genes, and (4) DNA-repair genes (caretaker genes).

17. Contrast oncogenes and tumor suppressor genes in terms of dominance and number of alleles that must be altered.

    Oncogenes act in a dominant fashion — a single activated (mutated) allele is sufficient (gain of function). Tumor suppressor genes are typically recessive at the cellular level — BOTH alleles must be inactivated (loss of function), as described by Knudson's two-hit hypothesis.

18. Explain Knudson's two-hit hypothesis using retinoblastoma.

    For a tumor suppressor gene like RB, both alleles must be inactivated ('two hits'). In hereditary retinoblastoma, one mutant RB allele is inherited (first hit in all cells), so a single somatic second hit causes bilateral, early tumors. In sporadic cases, both hits must occur somatically in the same cell, giving unilateral, later disease.

19. What is the function of the p53 gene and why is it called the 'guardian of the genome'?

    $p53$ (TP53) is a tumor suppressor that senses DNA damage and arrests the cell cycle at the $\text{G}_1/\text{S}$ checkpoint to allow repair, or triggers apoptosis if damage is irreparable. Loss of both alleles allows damaged DNA to replicate, making $TP53$ the most commonly mutated gene in human cancers.

20. Name the major oncogene functional categories with one example each.

    Growth factors (e.g., PDGF/SIS), growth factor receptors (e.g., ERBB2/HER2, RET), signal transducers (e.g., RAS — most common oncogene; ABL), nuclear transcription factors (e.g., MYC), and cell-cycle regulators (e.g., cyclin D/CDK4).

21. List the classic 'hallmarks of cancer' that malignant cells acquire.

    Self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis, limitless replicative potential (telomerase), sustained angiogenesis, tissue invasion and metastasis — plus enabling traits of genomic instability, tumor-promoting inflammation, altered metabolism (Warburg effect), and immune evasion.

22. What is the Warburg effect in cancer metabolism?

    The Warburg effect is the tendency of tumor cells to rely on aerobic glycolysis — high glucose uptake and conversion to lactate even in the presence of oxygen — rather than oxidative phosphorylation, providing metabolic intermediates for rapid biosynthesis and growth. It underlies FDG-PET tumor imaging.

23. Define paraneoplastic syndrome and give two classic examples.

    A paraneoplastic syndrome is a symptom complex in cancer patients not explained by local/metastatic tumor spread or by hormones native to the tissue. Examples: Cushing syndrome from ectopic ACTH (small cell lung carcinoma) and hypercalcemia from PTH-related peptide (squamous cell lung carcinoma).

24. Define grading versus staging of a malignant tumor.

    Grading is based on histologic degree of differentiation and mitotic activity of tumor cells (how abnormal they look). Staging is based on anatomic extent — using the TNM system: T = size/extent of primary Tumor, N = regional lymph Node involvement, M = distant Metastasis. Staging is generally of greater clinical/prognostic value.

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