A 56-year-old male visits a surgery OPD with complaints of difficulty in passage of urine especially on straining. Based on his…

(a) Benign hypertrophy of the prostate: anatomical basis, relations and supply

Anatomical basis of the urinary problems. The prostate surrounds the first 3 cm of the urethra just below the bladder neck. In benign hypertrophy the periurethral (transition) zone and the median lobe enlarge. The median lobe bulges into the bladder and acts like a ball valve over the internal urethral orifice, and the enlarged lateral lobes squeeze the prostatic urethra into a slit. Resistance to flow rises, so the patient has hesitancy, straining, a weak stream and incomplete emptying. Residual urine can cause infection, stones, trabeculated bladder and, later, hydronephrosis.

Relations of the prostate: Base (above): the bladder neck, with the seminal vesicles and vasa deferentia behind it. Apex (below): the urogenital diaphragm with the external urethral sphincter. Anterior surface: the pubic symphysis, separated by the retropubic space (of Retzius) containing fat and the prostatic venous plexus, and held by the puboprostatic ligaments. Posterior surface: the rectum, separated from it by Denonvilliers' fascia (rectovesical septum). This is why the gland can be palpated on digital rectal examination. Inferolateral surfaces: the levator ani (puboprostatic part), with the prostatic sheath and venous plexus in between.

Blood supply. The arteries are the prostatic branches of the inferior vesical artery (the main supply), with contributions from the middle rectal and internal pudendal arteries. The veins form the prostatic venous plexus around the gland, which drains to the internal iliac veins and also communicates with the vertebral venous plexus of Batson, explaining spread of prostatic cancer to the spine. Lymphatic drainage is chiefly to the internal iliac nodes and also to the sacral and external iliac nodes.

(b)(i) Biochemical role of copper and Wilson disease

Copper is a cofactor for cytochrome c oxidase (complex IV, respiration), Cu/Zn superoxide dismutase (antioxidant defence), lysyl oxidase (cross-linking of collagen and elastin), ceruloplasmin (ferroxidase that oxidises Fe²⁺ to Fe³⁺ for transferrin), tyrosinase (melanin) and dopamine β-hydroxylase (noradrenaline synthesis). Ceruloplasmin carries about 90% of plasma copper.

Wilson disease is an autosomal recessive defect of the ATP7B copper-transporting ATPase of the liver. Biliary copper excretion fails and copper is not loaded onto ceruloplasmin, so copper accumulates in the liver (hepatitis, cirrhosis), brain, especially the basal ganglia (tremor, dysarthria, psychiatric change) and cornea (Kayser-Fleischer ring).

Helpful biochemical investigations are: low serum ceruloplasmin, low total serum copper with raised free (non-ceruloplasmin) copper, raised 24-hour urinary copper, and raised hepatic copper on liver biopsy (over 250 μg/g dry weight). The Kayser-Fleischer ring is a slit-lamp finding, and genetic analysis of ATP7B confirms the diagnosis.

(b)(ii) Genetic code, wobble hypothesis and post-translational modification

The genetic code is the set of rules by which a triplet of nucleotides (a codon) in mRNA specifies one amino acid. There are 64 codons, of which 61 code for amino acids and 3 (UAA, UAG, UGA) are stop signals; AUG codes for methionine and starts translation. The code is triplet, non-overlapping, commaless, degenerate (several codons per amino acid), unambiguous and nearly universal (mitochondria are an exception).

Wobble hypothesis (Crick). The first two bases of the codon pair strictly with the anticodon, but pairing at the third codon base is relaxed. The 5′ anticodon base can pair with more than one base: G with C or U, U with A or G, and inosine with U, C or A. So one tRNA can read two or three synonymous codons, and about 32 tRNAs suffice to read the 61 sense codons.

Post-translational modifications change a protein after synthesis and control its activity, stability, location and folding. Examples are proteolytic cleavage (proinsulin to insulin, zymogens), phosphorylation of serine, threonine and tyrosine, glycosylation, hydroxylation of proline in collagen, γ-carboxylation of clotting factors, ubiquitination for degradation, lipid attachment and disulfide bond formation.

(c) Physiological changes in pregnancy

Genital organs. The uterus grows from about 50 g to 1000 g under oestrogen and progesterone, by hypertrophy and hyperplasia of the myometrium, and its blood flow rises from about 50 to 500–750 mL/min at term. The isthmus softens (Hegar's sign), the cervix becomes soft and bluish (Goodell's sign), a mucus plug forms, and the vagina becomes congested and bluish (Chadwick's sign) with increased acidic secretion. The corpus luteum secretes progesterone until the placenta takes over at 10 to 12 weeks, and ovulation stops.

Blood and its constituents. Plasma volume rises by 40 to 50% but red cell mass by only 20 to 30%, so haemodilution causes physiological anaemia (haemoglobin falls to about 11 g/dL), and iron and folate needs increase. Total blood volume rises by 30 to 50%. White cell count rises (up to about 15 000/μL, more in labour), platelets fall slightly, and fibrinogen and clotting factors VII, VIII and X increase, giving a hypercoagulable state with a raised ESR. Plasma albumin falls.

Cardiovascular system. Cardiac output rises by 30 to 50%, peaking at 28 to 32 weeks, through a rise in stroke volume and a heart rate increase of 10 to 20 beats/min. Progesterone lowers systemic vascular resistance, so blood pressure, especially diastolic, falls in the second trimester and returns near normal by term. The heart is displaced upward and to the left, a soft systolic flow murmur is common, and venous pressure in the legs rises, causing varicose veins and oedema. In the supine position the uterus compresses the inferior vena cava and aorta, which may cause supine hypotension syndrome.