The presence of dyspnoea makes alpha-1 antitrypsin deficiency the more likely diagnosis as biliary atresia does not cause respiratory symptoms. Deficiency of the enzyme alpha-1 antitrypsin causes uninhibited elastase activity and a decrease in elastic tissue. This causes liver cirrhosis leading to an elevation of conjugated bilirubin and emphysema in the lungs.

Rhesus disease, hereditary spherocytosis and breast milk jaundice cause an elevation of unconjugated bilirubin thus ruling it out in this case. Breast milk jaundice occurs due to an inability of the newborn to metabolize the proteins in breast milk.

Rhesus disease occurs when an Rh negative mother gives birth to an Rh positive baby. The jaundice would have been accompanied by anaemia and oedema.

Hereditary spherocytosis occurs due to extravascular haemolysis as defective RBCs are removed by the spleen. The patient would present with jaundice, splenomegaly and possibly an aplastic crisis (if Parvovirus B19 infection).

The following nerves provide cutaneous innervation to the scrotum, and other anatomic structures:

The perineal nerve supplies the muscles in the urogenital triangle, and the skin on the posterior surface of the scrotum (or labia majora).

The genital branch of the genitofemoral nerve supplies the cremaster muscle, the skin over the anterior surface of the thigh, and the anterolateral surface of the scrotum.

The ilioinguinal nerve supplies the external oblique, internal oblique, transversus abdominis, skin of the upper medial aspect of thigh, the root of the penis and the anterior surface of the scrotum in the male, and the mons pubis and labia majora in the female.

The posterior cutaneous nerve of the thigh, or posterior femoral cutaneous nerve, supplies the skin over the lower medial quadrant of the buttock, the inferior skin of the scrotum or labium majus, and the back of the thigh and the upper part of the leg.

Chlorhexidine is an anti-staphylococcal agent. Cleaning is the removal of foreign material from areas or objects to a point at which they are visually free from debris.  Disinfection is the reduction in the number of infectious particles. Isopropyl alcohol is not effective against C. difficile spores. Autoclaving is a method of sterilisation.

Insulin has a number of effects on glucose metabolism, including:
Inhibition of glycogenolysis and gluconeogenesis
Increased glucose transport into fat and muscle
Increased glycolysis in fat and muscle
Stimulation of glycogen synthesis
By inhibiting gluconeogenesis, insulin maintains the availability of amino acids as substrates for protein synthesis. Thus, insulin supports protein synthesis through direct and indirect mechanisms.

Because the middles of the shafts of the ribs are lower than either the anterior or posterior end, elevation of the ribs also moves the middles of the shafts laterally. This ‘bucket handle’ upwards and lateral movement increases the lateral dimensions of the thorax.

The arm should be placed in a poly-sling that should be worn for about two weeks. A physiotherapist may give gentle movements for the arm to help in reducing stiffness and in relieving the pain. It is important that the patient must avoid positions that could cause re-dislocation.
The most important position to avoid is the arm being held out at 90 degrees to the side with the palm facing upwards, especially if a force is being applied.

Gentamicin, an aminoglycoside antibiotic, acts by binding to the 30S subunit of the bacterial ribosome inhibiting the binding of aminoacyl-tRNA and thus preventing initiation of protein synthesis.

Vancomycin inhibits cell wall peptidoglycan formation by binding the D-Ala-D-Ala portion of cell wall precursors.

Penicillins and cephalosporins are the major antibiotics that inhibit bacterial cell wall synthesis. They inactivate transpeptidases that help cross-link peptidoglycans in cell walls.

Metronidazole and the other 5-nitroimidazole agents inhibit nucleic acid synthesis by forming toxic free radical metabolites in the bacterial cell that damage DNA.

Ciprofloxacin inhibits prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV.

Factors decreasing FRC:
Restrictive ventilatory defects e.g. pulmonary fibrosis
Posture – lying supine
Increased intra-abdominal pressure (e.g. obesity, pregnancy, ascites)
Reduced muscle tone of diaphragm e.g. muscle relaxants in anaesthesia, neuromuscular disease

Hartmann’s pouch is a diverticulum that can occur at the neck of the gallbladder. It is one of the rarest congenital anomalies of the gallbladder. Hartmann’s gallbladder pouch is a frequent but inconsistent feature of normal and pathologic human gallbladders. It is caused by adhesions between the cystic duct and the neck of the gallbladder. As a result, it is classified as a morphologic rather than an anatomic entity.

There is a significant association between the presence of Hartmann’s pouch and gallbladder stones. It is the most common location for gallstones to become lodged and cause cholestasis.

Parathyroid hormone (PTH) is a peptide hormone synthesised by the chief cells of the parathyroid glands, located immediately behind the thyroid gland. PTH is primarily released in response to decreasing plasma [Ca2+] concentration. PTH acts to increase plasma calcium levels and decrease plasma phosphate levels.
Parathyroid hormone (PTH) acts to increase calcium reabsorption in the distal tubule of the nephron (by activating Ca2+entry channels in the apical membrane and the Ca2+ATPase pump in the basolateral membrane) and increase phosphate excretion by inhibiting reabsorption in the proximal tubule of the nephron.

Extensor carpi radialis brevis is a fusiform muscle found in the lateral part of the posterior forearm. Together with anconaeus, brachioradialis, extensor carpi radialis longus, extensor digitorum, extensor digiti minimi and extensor carpi ulnaris, it belongs to the superficial forearm extensor group. Extensor carpi radialis brevis originates from the lateral epicondyle of humerus via the common extensor tendon. This is a common origin that it shares with the extensor digitorum, extensor digiti minimi and extensor carpi ulnaris muscles. Some fibres also originate from the lateral intermuscular septum, a thick aponeurosis that covers the muscle itself, and from the radial collateral ligament.

The muscle courses inferiorly, giving off a long tendon in the middle of the forearm which descends towards the dorsal hand. The tendon passes through a groove on the posterior surface of radius, deep to the extensor retinaculum. After traversing the extensor retinaculum space, the tendon inserts into the posterior aspect of the base of the third metacarpal bone.

Extensor carpi radialis brevis is innervated directly by the radial nerve (C5- C8), or sometimes from its deep branch/posterior interosseous nerve. The radial nerve stems from the posterior cord of the brachial plexus.

The muscle is vascularized by the radial recurrent artery, radial artery and deep brachial artery (via its radial collateral branch).

Extensor carpi radialis brevis works together with extensor carpi ulnaris and extensor carpi radialis longus to extend the hand at the wrist joint. This action is vital in a sequence of muscle contractions needed for clenching a fist or making a grip. When performing these functions, wrist extension blocks the flexor muscles from on acting upon the hand. Instead, flexors act only on the digits, thereby flexing them and producing an effective hand grip, such as that seen in a tennis backhand. When the extensor carpi radialis brevis muscle contracts together with extensor carpi radialis longus and flexor carpi radialis, it contributes to producing hand abduction (radial deviation).

Multiple myeloma is a clonal abnormality affecting plasma cells in which there is an overproduction of functionless immunoglobulins. The most common patient complaint is bone pain, especially in the back and ribs. Anaemia and renal failure are common, along with hypercalcemia. Hypercalcemia may lead to an altered mental status, as in this case.

Chronic lymphocytic leukaemia occurs due to the overproduction of lymphocytes, usually B cells. CLL may present with an asymptomatic elevation of B cells. Patients are generally more than 50 years old and present with non-specific fatigue and weight loss symptoms.

There is no history of alcohol abuse in this case. Furthermore, patients with a history of alcohol abuse may have signs of liver failure, which are not present here.

Metastatic prostate cancer would most often cause lower backache as it metastasises first to the lumbar spine via the vertebral venous plexus.

A patient with Vitamin B12 deficiency would have anaemia, megaloblastic, hypersegmented neutrophils, and signs of peripheral neuropathy.

Antispasmodics, such as antimuscarinics, may be used in the management of irritable bowel syndrome. Other antispasmodics used include direct-acting smooth muscle relaxants such as mebeverine, alverine, and peppermint oil. Antispasmodics are contraindicated in bowel obstruction and severe inflammatory bowel disease. Antispasmodics are occasionally of value in treating abdominal cramp associated with diarrhoea but they should not be used for primary treatment. Antispasmodics should be avoided in young children with gastroenteritis because they are rarely effective and have troublesome side effects. Antimuscarinics are contraindicated in urinary retention.

Laboratory results often show that:
PFA-100 test results are abnormal.
Low levels of factor VIII (if a factor VIII/VWF binding assay is conducted)
APTT is Prolonged (or normal)
PT is normal
VWF values are low.
Defective Platelet aggregation
The platelet count is normal.

Posterior inferior cerebellar artery (PICA) occlusion is characterised by vertigo, ipsilateral hemiataxia, dysarthria, ptosis and miosis. PICA occlusion causes infarction of the posterior inferior cerebellum, inferior cerebellar vermis and lateral medulla.

Dopamine is a catecholamine that occurs naturally and is used to treat low cardiac output, septic shock, and renal failure. It is both adrenaline and noradrenaline’s immediate precursor.

Dopamine acts on D1 and D2 dopamine receptors in the renal, mesenteric, and coronary beds at low doses (1-5 g/kg/min). Dopamine causes a significant decrease in renal vascular resistance and an increase in renal blood flow at these doses. Within this dose range, it is also involved in central modulation of behaviour and movement.

Dopamine stimulates beta- and alpha-adrenergic receptors directly and indirectly at higher doses. Beta-stimulation predominates at a rate of 5-10 g/kg/min, resulting in a positive inotropic effect that increases cardiac output and coronary blood flow. Alpha-stimulation predominates at infusion rates greater than 15 g/kg/min, resulting in peripheral vasoconstriction and an increase in venous return and systolic blood pressure.

Below is a summary of the mechanisms and effects of various inotropic agents:
Inotrope
Mechanism
Effects
Adrenaline (epinephrine)
Beta-1 and -2 agonist at increasing doses;
Alpha-agonist at high doses
Increased cardiac output;
Vasoconstriction at higher doses
Noradrenaline (norepinephrine)
Mainly alpha-agonist;
Beta-1 and -2 agonist at increasing doses
Vasoconstriction;
Some increased cardiac output
Dopamine
Dopamine agonist at low doses;
Beta-1 and -2 agonist at increasing doses;
Alpha-agonist at high doses
Increased cardiac output;
Vasoconstriction at higher doses
Dobutamine
Mainly beta-1 agonist
Increased cardiac output

Compliance changes at different lung volumes. Initially at lower lung volumes the compliance of the lung is poor and greater pressure change is required to cause a change in volume. This occurs if the lungs become collapsed for a period of time. At functional residual capacity (FRC) compliance is optimal since the elastic recoil of the lung tending towards collapse is balanced by the tendency of the chest wall to spring outwards. At higher lung volumes the compliance of the lung again becomes less as the lung becomes stiffer. At all volumes, the base of the lung has a greater compliance than the apex. Patients with emphysema have increased compliance. Compliance is affected by a person’s age, sex and height.

The Likelihood Ratio (LR) is the likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that that same result would be expected in a patient without the target disorder.

The LR is used to assess how good a diagnostic test is and to help in selecting an appropriate diagnostic tests or sequence of tests. They have advantages over sensitivity and specificity because they are less likely to change with the prevalence of the disorder, they can be calculated for several levels of the symptom/sign or test, they can be used to combine the results of multiple diagnostic test and they can be used to calculate post-test probability for a target disorder.

A LR greater than 1 produces a post-test probability which is higher than the pre-test probability. An LR less than 1 produces a post-test probability which is lower than the pre-test probability. When the pre-test probability lies between 30 and 70 per cent, test results with a very high LR (say, above 10) rule in disease. An LR below 1 produces a post-test probability les than the pre-test probability. A very low LR (say, below 0.1) virtually rules out the chance that the patient has the disease.

Chickenpox infection in neonates, adults/adolescents and pregnant women is associated with more severe disease. Varicella zoster pneumonitis typically occurs in pregnant women or immunocompromised individuals and is associated with a high mortality. A live attenuated-virus vaccine is available and recommended for non-immune healthcare workers but is not part of the routine childhood immunisation schedule. Antiviral treatment is not typically recommended in childhood chickenpox but is indicated for shingles.

In the absence of any contra-indications, high-dose NSAIDs are the first-line treatment for acute gout. Naproxen 750 mg as a stat dose followed by 250 mg TDS is a commonly used and effective regime.
Aspirin should not be used in gout as it reduces the urinary clearance of urate and interferes with the action of uricosuric agents. Naproxen, Diclofenac or Indomethacin are more appropriate choices.
Allopurinol is used prophylactically, preventing future attacks by reducing serum uric acid levels. It should not be started in the acute phase as it increases the severity and duration of symptoms.
Colchicine acts on the neutrophils, binding to tubulin to prevent neutrophil migration into the joint. It is as effective as NSAIDs in relieving acute attacks. It also has a role in prophylactic treatment if Allopurinol is not tolerated.
NSAIDs are contra-indicated in heart failure as they can cause fluid retention and congestive cardiac failure. Colchicine is the preferred treatment in patients with heart failure or those who are intolerant of NSAIDs.

Natural Killer (NK) Cells are lymphocytes in the same family as T and B cells, which come from a common progenitor. They are cytotoxic CD8 positive cells that do not have the T-cell receptor. They are very big cells with cytoplasmic granules and are designed to kill target cells with a low level of expression of HLA class I molecules.
Examples include during a viral infection or on a malignant cell. NK cells display several receptors for HLA molecules on their surface, and when HLA is expressed on the target cell, these deliver an inhibitory signal into the NK cell. Absent HLA molecules on the target cell cause this inhibitory signal to get lost and as a result, the NK cell can then kill its target. Also, NK cells display antibody-dependent cell-mediated cytotoxicity, where antibody binds to antigen on the surface of the target cell. The NK cells then bind to the Fc portion of the bound antibody and kill the target cell.

A pareto diagram, or pareto chart, consists of a vertical bar graph in which values are plotted in decreasing order of relative frequency from left to right. The independent variables on the chart are shown on the horizontal axis and the dependent variables are portrayed as the heights of bars.

A point-to-point graph, which shows the cumulative relative frequency, may be superimposed on the bar.

Because the values of the statistical variables are placed in order of relative frequency, the graph clearly reveals which factors have the greatest impact and where attention is likely to yield the greatest benefit. It is extremely useful for analysing what problems need attention first, because the taller bars on the chart clearly illustrate which variable have the greatest cumulative effect on a given system.

Febrile transfusion reactions presents with an unexpected temperature rise (≥ 38ºC or ≥ 1ºC above baseline, if baseline ≥ 37ºC) during or shortly after transfusion. It is usually an isolated finding and the fever is accompanied by chills and malaise occasionally.

Allergic reaction is commonly caused by foreign plasma proteins but may be due to anti-IgA. Allergic type reactions usually present with urticaria, pruritus, hives. Associations include laryngeal oedema or bronchospasm.

Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.

Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.

Transfusion-related lung injury (TRALI) is a form of acute respiratory distress caused by the donor plasma containing antibodies against the patient’s leukocytes. It is defined as hypoxia and bilateral pulmonary oedema that occurs within 6 hours of a transfusion in the absence of other causes of acute lung injury. Clinical features include Breathlessness, cough, frothy sputum, hypertension or hypotension, hypoxia and fever. Chest X-ray shows multiple perihilar nodules with infiltration of the lower lung fields.

Foveolar cells, also known as gastric mucous-neck cells, are cells that line the stomach mucosa and are found in the necks of the gastric pits. Mucus and bicarbonate are produced by these cells, which prevent the stomach from digesting itself. At pH 4, the mucous allows the acid to penetrate the lining, while below pH 4, the acid is unable to do so. Viscous fingering is the term for this procedure.

The table below summarizes the many cell types found in the stomach, as well as the substances secreted by each cell type and the function of the secretion:

Cell type/ Substance secreted/ Function of secretion
Parietal cells/ Hydrochloric acid/ Kills microbes and activates pepsinogen
Parietal cells/ Intrinsic factor/Binds to vitamin B12 and facilitates its absorption
Chief cells/ Pepsinogen/ Protein digestion
Chief cells/ Gastric lipase/ Fat digestion
G-cells/ Gastrin/ Stimulates gastric acid secretion
Enterochromaffin-like cells (ECL cells) /Histamine/ Stimulates gastric acid secretion
Mucous-neck cells/ Mucous and bicarbonate/ Protects stomach epithelium from acid
D-cells/ Somatostatin/ Inhibits gastric acid secretion

Dietary fat is chiefly composed of triglycerides (esters of free fatty acids and glycerol which may be saturated or unsaturated). The essential fatty acids are linoleic acid and alpha-linoleic acid, which cannot be manufactured in the body. Dietary fat provides 37 kJ (9 kcal) of energy per gram. Fats are digested almost entirely in the small intestine and are only released from the stomach into the duodenum at the rate at which they can be digested.
Pancreatic lipase is the most significant enzyme for fat digestion. In the duodenum fat is emulsified by bile acids, a process where larger lipid droplets are broken down into much smaller droplets providing a greater surface area for enzymatic digestion. Micelles are arranged so that hydrophobic lipid molecules lie in the centre, surrounded by bile acids arranged such the outer region is hydrophilic. Dietary and synthesised lipids are incorporated into chylomicrons in the Golgi body, which are exocytosed from the basolateral membrane to enter lacteals and thus the lymphatic system.

The most frequent cause of red eye is conjunctivitis. It is caused by inflammation of the conjunctiva which can be infective or allergic and accounts for about 35% of all eye problems presenting to general practice.

Viral conjunctivitis is commonly caused by adenoviruses and it is the most common infectious conjunctivitis.

The common bacterial causes of conjunctivitis are Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus.

The clinical features of infective conjunctivitis include:
Acute onset of conjunctival erythema
Feeling ‘grittiness’, ‘foreign body’ or ‘burning’ sensation in the eye.
Watering and discharge which may cause transient blurring of vision

Features of viral conjunctivitis include: watery and non-purulent eye discharge, lid oedema, follicles present on eyelid eversion, petechial subconjunctival haemorrhages and pseudomembranes may be seen on the tarsal conjunctival surfaces.

This patients features are consistent with a viral aetiology, and the most likely causative organism is adenovirus,

Chronic kidney disease (CKD) is a disorder in which kidney function gradually deteriorates over time. It’s fairly prevalent, and it typically remains unnoticed for years, with only advanced stages of the disease being recognized. There is evidence that medication can slow or stop the progression of CKD, as well as lessen or prevent consequences and the risk of cardiovascular disease (CVD).

CKD is defined as kidney damage (albuminuria) and/or impaired renal function (GFR 60 ml/minute per 1.73 m2) for three months or longer, regardless of clinical diagnosis.

A prolonged decline in GFR of 25% or more with a change in GFR category within 12 months, or a sustained drop in GFR of 15 ml/minute/1.73 m² per year, is considered accelerated CKD progression.
End-stage renal disease (ESRD) is defined as severe irreversible kidney impairment with a GFR of less than 15 ml/minute per 1.73 m² and a GFR of less than 15 ml/minute per 1.73 m².

Flexor carpi radialis is innervated by the median nerve.

Gastric emptying is decreased by:
Enterogastric inhibitory reflexes stimulated by – Distension of the duodenum, The presence of fats in the duodenum (by stimulating release of cholecystokinin), A fall in the pH of chyme in the duodenum, An increase in the osmolality of chyme in the duodenum, Irritation of the mucosal lining of the duodenum, Hormones: Cholecystokinin, Secretin

The hookworm life cycle begins with the passage of eggs from an adult host into the stool. Hookworm eggs hatch in the soil to release larvae that mature into infective larvae. Infection is usually transmitted by larval penetration into human skin (duodenal infection may also be transmitted by the oral route). From the skin, larvae migrate into the blood vessels and are carried to the lungs, where they penetrate the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed.