(a) (i) Describe the following regarding the knee joint : (I) All movements including locking and unlocking with muscles…

(a)(i) Knee joint: movements, locking and unlocking, and the cruciate ligaments

(I) Movements. The knee is a modified hinge (condylar synovial) joint with a small rotational component. It permits flexion (0 to about 135°), extension (0°, with slight hyperextension) and rotation of the tibia when the knee is flexed.

Flexion: hamstrings (biceps femoris, semitendinosus, semimembranosus), assisted by gracilis, sartorius, gastrocnemius and popliteus. Extension: quadriceps femoris, with tensor fasciae latae helping to steady the extended knee through the iliotibial tract. Medial rotation of the flexed tibia: popliteus, semimembranosus, semitendinosus, sartorius and gracilis. Lateral rotation of the flexed tibia: biceps femoris.

Locking (screw-home). In the last 20° of extension the tibia rotates laterally on the femur (or the femur rotates medially if the foot is fixed), because the medial femoral condyle has a longer articular surface. The anterior cruciate ligament becomes taut, the joint surfaces become fully congruent, and the knee is a rigid column that stands without muscle effort. Quadriceps, especially vastus medialis, completes the movement.

Unlocking. Popliteus contracts to rotate the tibia medially (or the femur laterally on a fixed foot) and slackens the ligaments, so flexion can begin.

(II) Cruciate ligaments. They lie inside the capsule but outside the synovial cavity and cross like an X. Anterior cruciate ligament (tibia anterior to femur, lateral condyle): prevents anterior displacement of the tibia (anterior drawer), is tight in extension, resists hyperextension and medial tibial rotation. Posterior cruciate ligament (tibia posterior to femur, medial condyle): prevents posterior displacement of the tibia, is tight in flexion, and stops the femur sliding forward on the tibia, which is important when walking downhill or downstairs. Together they act as a four-bar linkage that makes the femur roll back on the tibia during flexion, and they guide the rolling-gliding movement.

(a)(ii) Carpal tunnel syndrome

(I) Causes and structure involved. The carpal tunnel is a fibro-osseous tunnel formed by the carpal bones (scaphoid and trapezium radially; pisiform and hook of hamate ulnarly) with the flexor retinaculum as its roof. It contains the median nerve and nine tendons: four each of flexor digitorum superficialis and profundus, and flexor pollicis longus. The median nerve is compressed. Causes are anything that narrows the tunnel or swells its contents: repetitive wrist use, wrist fractures (Colles'), rheumatoid arthritis and tenosynovitis, pregnancy and fluid retention, hypothyroidism, diabetes, acromegaly, obesity and amyloidosis; many cases are idiopathic.

(II) Clinical features. Pain, tingling and numbness over the thumb, index, middle and lateral half of the ring finger, typically worse at night and relieved by shaking the hand (flick sign). Later there is weakness of thumb abduction and opposition and wasting of the thenar eminence (abductor pollicis brevis, opponens pollicis, flexor pollicis brevis superficial head). Sensation over the thenar eminence is spared because the palmar cutaneous branch arises proximal to the tunnel. Tinel's sign (tapping over the nerve), Phalen's test (wrist flexion for 60 seconds) and Durkan's compression test reproduce the symptoms; nerve conduction studies confirm delayed median conduction.

(b)(i) Polymerase chain reaction (PCR)

Principle. PCR (Kary Mullis, 1983) amplifies a chosen DNA segment in vitro by repeated cycles of heat denaturation, primer binding and enzymatic copying. The reaction mix contains template DNA, two specific primers flanking the target, the four dNTPs, heat-stable Taq polymerase (from Thermus aquaticus), Mg²⁺ and buffer.

Steps in each cycle: Denaturation at 94–98 °C separates the double strands. Annealing at 50–65 °C lets the primers bind to their complementary ends. Extension at about 72 °C lets Taq polymerase add nucleotides 5′ to 3′ from each primer. Each cycle doubles the target, so 30 cycles give about 2³⁰ (10⁹) copies, seen as a band on gel electrophoresis.

Clinical applications: detection of microbes (TB by CBNAAT, which is real-time PCR, HIV and hepatitis B and C viral load, SARS-CoV-2 by RT-PCR); genetic diseases (sickle cell, thalassaemia, cystic fibrosis, Duchenne dystrophy) and prenatal diagnosis; cancer markers (BCR-ABL in chronic myeloid leukaemia); HLA typing; forensic DNA fingerprinting and paternity testing.

(b)(ii) Serum biochemical markers of cholestasis

Cholestasis is impaired bile flow and gives an obstructive pattern: Alkaline phosphatase is raised, often more than three times normal; it also rises in bone disease and pregnancy. Gamma-glutamyl transferase is raised and confirms a hepatobiliary source of ALP; 5′-nucleotidase serves the same purpose. Conjugated (direct) bilirubin is raised, with bilirubin in urine and absent urobilinogen. Serum bile acids and cholesterol (with lipoprotein X) are raised. AST and ALT are only mildly raised, unlike hepatocellular injury. Prothrombin time may be prolonged and corrects with parenteral vitamin K.

(c)(i) Intrinsic regulation of cardiac output

Cardiac output = heart rate × stroke volume (about 5 L/min at rest). The heart can adjust its output without nerves or hormones in these ways:

Frank-Starling law (heterometric regulation). A greater venous return stretches the ventricle, so end-diastolic volume rises and the ventricle contracts more forcefully, up to an optimal sarcomere length of about 2.2 μm, through better actin-myosin overlap and greater troponin C sensitivity to calcium. Stroke volume therefore matches venous return and the two ventricles stay balanced. Homeometric regulation. The Anrep effect is a slow rise in contractility after a sudden rise in afterload, and the Bowditch (treppe) effect is the rise in force when heart rate increases. Intrinsic rate. Stretch of the sinoatrial node raises the heart rate by 10 to 15%. Extrinsic control by the sympathetic and vagal nerves and catecholamines modifies these responses.

(c)(ii) Factors regulating erythropoiesis

Erythropoietin is the main regulator. About 90% is made by peritubular interstitial cells of the kidney and 10% by the liver, in response to hypoxia through hypoxia-inducible factor. It acts on BFU-E and CFU-E progenitors to promote proliferation and maturation, and the rising red cell mass relieves hypoxia and switches EPO off (negative feedback). Nutrients: iron for haem, vitamin B12 and folic acid for DNA synthesis, with protein, copper and vitamin B6; their lack causes anaemia. Hormones: androgens, thyroxine, growth hormone and cortisol stimulate; oestrogens depress. Cytokines (IL-3, stem cell factor, GM-CSF) support progenitors; inflammation lowers red cell production through hepcidin and cytokines.