(a) (i) 1. Name the ligaments of ovary and their role in ovarian torsion and its complications. 2. Explain the surgical…

(a)(i) Ligaments of the ovary, ovarian torsion and the ovarian fossa (10 marks)

1. Ligaments of the ovary and ovarian torsion.

• The suspensory ligament of the ovary (infundibulopelvic ligament) is a peritoneal fold that attaches the upper (tubal) pole to the pelvic brim and posterior abdominal wall. It carries the ovarian artery, vein, nerves and lymphatics.
• The ovarian ligament (ligament of the ovary proper) is a fibromuscular cord that joins the lower (uterine) pole to the lateral wall of the uterus, below the attachment of the uterine tube.
• The mesovarium, a short peritoneal fold of the broad ligament, attaches the anterior border of the ovary. The tubo-ovarian (fimbrial) ligament joins the ovary to the fimbriated end of the tube.

Role in torsion. The ovary is anchored only by the suspensory and ovarian ligaments, so it hangs on a narrow vascular pedicle. When the ovary is enlarged (a cyst or tumour) or the ovarian ligament is long, it can twist on its pedicle, which includes these two ligaments and the ovarian vessels. The thin-walled veins are compressed first, so the ovary becomes congested and oedematous, and then the arterial supply is cut off. The complications are:

• Severe acute lower abdominal pain, nausea and vomiting.
• Haemorrhagic infarction, necrosis and gangrene of the ovary and often of the tube.
• Rupture of the ovary with peritonitis, adhesions, and loss of the ovary with reduced fertility.

2. Surgical importance of the relations of the ovarian fossa. The ovarian fossa is a shallow depression on the lateral pelvic wall. Its boundaries are the external iliac vessels superiorly, the obliterated umbilical artery anteriorly, the ureter and internal iliac artery posteriorly, and the origin of the uterine artery inferiorly. The obturator nerve and vessels, and the obturator internus muscle, form the floor. Their importance is:

• The obturator nerve lies in the floor, so ovarian disease (or an inflamed ovary) causes pain referred to the medial side of the thigh, and the nerve can be injured in dissection.
• The ureter runs behind the fossa, close to the ovarian vessels, and is at risk of injury during oophorectomy or ligation of the ovarian pedicle.
• The internal iliac artery and its branches, the uterine artery and the external iliac vessels, are at risk of haemorrhage in ovarian surgery.
• Lymph nodes (external iliac and obturator) drain the region, so they are involved in ovarian malignancy, and ovarian tumours in the fossa can be adherent to these structures.

(a)(ii) Sites of portosystemic anastomosis (10 marks)

The portal vein has no valves, and communications between its tributaries and systemic veins open when portal pressure rises (as in cirrhosis). The main sites are:

• Lower end of the oesophagus (gastro-oesophageal junction): the oesophageal tributaries of the left gastric vein (portal) communicate with the oesophageal veins that drain to the azygos and hemiazygos veins (systemic). They form oesophageal varices, which can bleed massively.
• Anal canal (anorectal junction): the superior rectal vein (portal, through the inferior mesenteric vein) communicates with the middle rectal vein (internal iliac vein) and the inferior rectal vein (internal pudendal to internal iliac vein) (systemic). They form internal haemorrhoids.
• Umbilicus (anterior abdominal wall): the paraumbilical veins (portal, in the falciform ligament and round ligament of the liver, joining the left portal vein) communicate with the superficial and inferior epigastric veins, the superior epigastric and the lateral thoracic veins (systemic). The dilated veins radiate from the umbilicus as caput medusae.
• Retroperitoneum (veins of Retzius): the colic veins of the ascending and descending colon, and veins of the duodenum, pancreas and liver (portal) communicate with the renal, lumbar, phrenic and gonadal veins (systemic).
• Bare area of the liver: the hepatic tributaries of the portal vein communicate with the phrenic veins of the diaphragm.
• Splenorenal: the splenic vein communicates with the left renal vein (spontaneous or surgical, in the lienorenal ligament).

(b)(i) Genetic code and its features (5 marks)

The genetic code is the set of rules by which the sequence of nucleotide triplets (codons) in mRNA specifies the sequence of amino acids in a protein. Its salient features are:

• It is a triplet code: three nucleotides make one codon.
• There are 64 codons, of which 61 code for the 20 amino acids (sense codons) and 3 (UAA, UAG, UGA) are stop (nonsense) codons.
• AUG is the initiator codon and codes for methionine.
• The code is degenerate (redundant): most amino acids have more than one codon, and only methionine and tryptophan have a single one. The wobble hypothesis explains this, since the third base of the codon pairs loosely with the first base of the anticodon.
• It is unambiguous (each codon specifies one amino acid), non-overlapping and comma-free (read continuously in one reading frame, in the 5′ to 3′ direction).
• It is nearly universal, the exceptions being in mitochondria (for example UGA codes for tryptophan, and AUA for methionine).

(b)(ii) Post-translational modifications (10 marks)

Post-translational modifications (PTMs) are the covalent changes made to a polypeptide after or during its synthesis, which are needed to make the protein active, stable or correctly located. They can be grouped by the residue involved:

• Serine, threonine and tyrosine: phosphorylation by protein kinases (and its reversal by phosphatases) controls enzyme activity, as in glycogen phosphorylase and the insulin receptor (tyrosine). Serine and threonine also carry O-linked glycosylation, as in mucins.
• Asparagine: N-linked glycosylation (at the Asn-X-Ser/Thr sequon, in the endoplasmic reticulum, using dolichol phosphate) is important for folding and targeting of glycoproteins.
• Proline and lysine: hydroxylation by prolyl and lysyl hydroxylases (needing vitamin C, iron and α-ketoglutarate) stabilises the collagen triple helix, and its failure causes scurvy. Lysyl oxidase (copper) converts lysine to allysine for collagen cross-linking. Lysine is also acetylated or methylated (histones) and ubiquitinated (marking proteins for proteasomal degradation).
• Glutamate: γ-carboxylation (vitamin K-dependent) of clotting factors II, VII, IX, X and proteins C and S, needed to bind calcium. Warfarin blocks it.
• Cysteine: disulphide bond formation (protein disulphide isomerase), as in insulin and immunoglobulins; prenylation (farnesylation) of Ras, and palmitoylation, which anchor proteins to membranes.
• Methionine and N-terminus: removal of the initiator methionine, and N-terminal acetylation.
• Proteolytic processing: removal of signal peptides, and conversion of proproteins and zymogens to the active form, for example proinsulin to insulin with C-peptide, and trypsinogen to trypsin.
• Non-enzymatic glycation of lysine, as in HbA1c, is a PTM of clinical use.

(c)(i) Measurement of cardiac output and the Frank–Starling law (5 + 5 = 10 marks)

Methods of measuring cardiac output (any two).

• Fick principle: the oxygen uptake of the body equals cardiac output times the arteriovenous oxygen difference across the lungs, so CO = VO₂/(CaO₂ − CvO₂). Oxygen consumption is measured by spirometry, arterial blood is taken from any artery, and mixed venous blood from the pulmonary artery (through a catheter). For example, with VO₂ = 250 mL/min, CaO₂ = 20 mL/100 mL and CvO₂ = 15 mL/100 mL, CO = 250/0.05 = 5000 mL/min = 5 L/min. It is accurate but invasive.
• Indicator (dye) dilution, Stewart–Hamilton: a known amount of dye (for example indocyanine green) is injected into a central vein and its concentration is recorded in an arterial sample over time. CO = amount of dye/(mean concentration × time, the area under the curve) × 60, with the recirculation tail extrapolated exponentially.
• Thermodilution: the same principle, using a bolus of cold saline injected into the right atrium and the temperature change recorded by a thermistor in the pulmonary artery (Swan–Ganz catheter). It is repeatable and widely used in intensive care.
• Doppler echocardiography (aortic velocity–time integral × valve area × heart rate) is a non-invasive alternative.

Role of the Frank–Starling law. Within physiological limits, the force of contraction (and stroke volume) of the ventricle is proportional to the initial length of its muscle fibres, that is the end-diastolic volume (preload). The heart therefore pumps out the blood that returns to it. The mechanism is the optimal overlap of actin and myosin at longer sarcomere length, and greater calcium sensitivity of troponin C (length-dependent activation). Its role is:

• It matches the outputs of the right and left ventricles, so pulmonary and systemic flow stay equal.
• It adjusts the stroke volume beat by beat to the venous return, in exercise, posture change and respiration.
• It is an intrinsic mechanism that works in a denervated (transplanted) heart, and acts to compensate in early heart failure.
• Beyond the limit of overstretch the curve flattens and falls (failing heart), and sympathetic stimulation or inotropic drugs shift the curve upwards and to the left.

(c)(ii) Golgi tendon organ (5 marks)

Structure. The Golgi tendon organ is an encapsulated, spindle-shaped stretch receptor (about 1 mm long) at the musculotendinous junction, in series with the muscle fibres. A thin connective tissue capsule surrounds the collagen bundles of the tendon that arise from about 10–20 muscle fibres. The endings of a large, myelinated Ib afferent fibre (12–20 µm) branch between and intertwine with these collagen fibres.

Function. It senses muscle tension, mainly that produced by active contraction, and responds less to passive stretch. When the tension rises, the collagen fibres straighten and compress the nerve endings, which fire, and the Ib fibre carries the impulse to the spinal cord. There it excites inhibitory interneurons, which inhibit the α motor neurons of the same muscle (autogenic inhibition, the inverse myotatic reflex) and facilitate its antagonist. The reflex therefore limits the tension and protects the muscle and tendon from damage, and it gives the central nervous system feedback for regulating the force of contraction. It also explains the clasp-knife reflex in spasticity. The muscle spindle, in contrast, lies in parallel with the muscle fibres and senses length.