(a) (i) A 55-year-old lady visits surgery OPD with a three month old history of a painless hard swelling in her left breast. On…

(a)(i) Breast sentinel node biopsy

The breast drains via lymphatics that converge on the subareolar (Sappey’s) plexus and along interlobular channels; about 75% of lymph reaches axillary nodes and 25% internal mammary nodes. In an upper inner quadrant tumour, first drainage may be to axillary level I/II nodes, but the medial position makes internal mammary nodes a significant sentinel site. Sentinel node biopsy is anatomically justified because tumour cells usually enter lymphatics and the sentinel node is the first filter; although skip metastasis is uncommon, the false-negative rate is about 5–10%. Pre-operative mapping is done by radiocolloid lymphoscintigraphy, and the node is confirmed intra-operatively with blue dye or a gamma probe. A negative sentinel node avoids unnecessary axillary lymph node dissection (and its lymphoedema and nerve injury) and guides axillary staging. SLNB is valid only when the axilla is clinically and ultrasonographically node-negative; here the lump is described as immovable, so fixity to the pectoral fascia versus the chest wall must be assessed, because chest-wall fixation (T4) or palpable nodes call for neoadjuvant therapy and axillary clearance rather than primary SLNB.

(a)(ii)(I) Knee ligaments and their roles

The knee is stabilised by the ACL, preventing anterior tibial translation and rotational instability; PCL, preventing posterior tibial translation; MCL, resisting valgus stress; LCL, resisting varus stress; oblique popliteal, reinforcing posterior capsule and limiting hyperextension/external rotation; arcuate popliteal, limiting varus/external rotation; patellar ligament, transmitting quadriceps force and stabilising patella; transverse ligament, connecting the anterior horns of the medial and lateral menisci; coronary (meniscotibial) ligaments, anchoring the menisci to the tibia; meniscofemoral ligaments (of Humphrey and Wrisberg), supporting the PCL and the lateral meniscus; and the medial and lateral patellar retinacula, stabilising the patella.

(a)(ii)(II) Likely structure

The case most likely shows an ACL tear. Anterior joint instability indicates loss of the main restraint to anterior tibial translation, and the cricket fall/twist mechanism is typical for a pivot-shift or non-contact ACL injury; Lachman/anterior drawer would be positive.

(b)(i) RIA and thyroid diagnosis

RIA is a competitive immunoassay: patient antigen competes with a fixed amount of radiolabelled antigen for limited antibody-binding sites; bound radioactivity is measured and compared with standards to quantify antigen. It is used for serum T3/T4, and related radioimmunoassay methods for TSH, to diagnose hyperthyroidism, hypothyroidism, subclinical disease and monitor treatment. Advantages are high sensitivity (pg/mL), specificity, small sample size and quantitative results. Disadvantages include radioactive waste, short shelf-life, expensive equipment, radiation safety concerns and limited use for large proteins. In current practice RIA has largely been replaced by non-isotopic chemiluminescence immunoassays (CLIA/ECLIA), and TSH is measured by sandwich (immunometric) assays.

(b)(ii) Haematopoietic vitamins

The haematopoietic vitamins are cobalamin (B12) and folate (B9), the principal ones; pyridoxine (B6), a cofactor of ALA synthase in haem synthesis, whose deficiency causes microcytic sideroblastic anaemia; vitamin C, which aids iron absorption and folate reduction; riboflavin (B2); vitamin E, which protects red-cell membranes (haemolytic anaemia in preterm infants); and vitamin A, which aids iron mobilisation. B12 is absorbed in the terminal ileum with intrinsic factor; it is a cofactor for methionine synthase and methylmalonyl-CoA mutase. Folate, as N5,N10-methylene-THF, is needed for thymidylate synthesis; B12-dependent methionine synthase regenerates THF. Deficiency of either impairs DNA synthesis in rapidly dividing erythroid precursors, causing megaloblastic anaemia and hypersegmented neutrophils. B12 deficiency also causes subacute combined degeneration because impaired methylmalonyl-CoA metabolism and methionine/SAM pathways damage myelin; folate deficiency usually does not.

(c)(i) Cell-mediated immunity

CMI develops when APCs (dendritic cells, macrophages, B cells) process antigen and present it on MHC II to CD4+ T cells or MHC I to CD8+ T cells; TCR-MHC recognition plus co-stimulation activates T cells. CD4+ Th1 cells secrete IL-2 and IFN-γ, activating macrophages; CD8+ CTLs kill infected or malignant cells by perforin-granzyme and Fas-FasL pathways; Th17 cells recruit neutrophils in mucosal defence, and Treg cells limit excessive responses. Clonal expansion and memory T cells provide long-term protection.

(c)(ii) Phagocytosis

Phagocytosis begins with chemotaxis of neutrophils/macrophages toward cytokines and complement. PRRs and opsonin receptors recognise opsonised microbes (IgG, C3b), attachment occurs, the cell engulfs the particle to form a phagosome. The phagosome fuses with lysosomes to form a phagolysosome, where ROS, NO and lysosomal enzymes kill the microbe; degraded antigen may be presented to T cells.

(c)(iii) Thrombocytes

Thrombocytes are formed by cytoplasmic fragmentation of megakaryocytes in bone marrow, aided by thrombopoietin; they circulate for 8–10 days. In haemostasis they adhere to exposed subendothelium via vWF, aggregate through ADP and TXA2, release granule contents, and form the primary platelet plug. They also support clot retraction and provide a phospholipid surface for coagulation.