HBsAg is the serological hallmark of HBV infection. After an acute exposure to HBV, HBsAg appears in serum within 1 to 10 weeks. Persistence of this marker for more than 6 months implies chronic HBV infection.

Anti-HBs is known as a neutralizing antibody, and confers long-term immunity. In patients with acquired immunity through vaccination, anti-HBs is the only serological marker detected in serum.

HBcAg is an intracellular presence in infected hepatocyte, thus it is not identified in the serum. During acute infection, anti-HBc IgM and IgG emerges 1–2 weeks after the presence of HBsAg along with raised serum aminotransferase and symptoms. After 6 months of acute infection, anti-HBc IgM wears off. Anti-HBc IgG continues to detect in both patients with resolved HBV infection and chronic hepatitis B.

Hepatitis D virus, also known as the delta hepatitis virus, is a defective ssRNA virus that requires HBV for replication. The infection can occur in one of two clinical forms, co-infection or superinfection. In a co-infection, the patient is simultaneously infected with HBV and HDV. In a superinfection, an HDV infection develops in a patient with a chronic HBV infection.

Penicillin is bactericidal and produces its antimicrobial action by preventing cross-linkage between the linear peptidoglycan polymer chains that make up the bacterial cell wall. This action inhibits cell wall synthesis.

Dopamine is a neurotransmitter and a metabolic precursor of the catecholamines. It acts on beta1-receptors in cardiac muscle increasing cardiac contractility, and increases renal perfusion by stimulating dopamine receptors in the renal vasculature. This is of benefit in cardiogenic shock where deterioration of renal function is common.

The latissimus dorsi muscle is a broad, flat muscle that occupies the majority of the lower posterior thorax. The muscle’s primary function is of the upper extremity but is also considered to be a respiratory accessory muscle.

Latissimus dorsi is a climbing muscle. With the arms fixed above the head, it can raise the trunk upwards, together with the help of pectoralis major.

Functionally, the latissimus dorsi muscle belongs to the muscles of the scapular motion. This muscle is able to pull the inferior angle of the scapula in various directions, producing movements on the shoulder joint (internal rotation, adduction and extension of the arm). It is innervated by the thoracodorsal nerve (C6 – C8) from the posterior cord of the brachial plexus, which enters the muscle on its deep surface.

Extensor indicis is a narrow, elongated muscle found in the posterior compartment of the forearm. It belongs to the deep extensors of the forearm, together with supinator, abductor pollicis longus, extensor pollicis longus, and extensor pollicis brevis muscles. It lacks the juncturae tendinum, which connects the extensor digitorum on the dorsal aspect of the hand.

Extensor indicis can be palpated by applying deep pressure over the lower part of the ulna while the index finger is extended. The main function of extensor indicis involves the extension of the index finger at the metacarpophalangeal and interphalangeal joints. As the index finger is one of the few fingers that have their own separate extensor muscle, it is able to extend independently from other fingers. Additionally, extensor indicis muscle produces a weak extension of the wrist.

Extensor indicis receives its nervous supply from posterior interosseous nerve, a branch of the radial nerve derived from spinal roots C7 and C8. The skin overlying the muscle is supplied by the same nerve, with fibres that stem from the spinal roots C6 and C7.

The superficial surface of the extensor indicis receives arterial blood supply from posterior interosseous branch of the ulnar artery, whereas its deep surface receives blood from perforating branches of the anterior interosseous artery.

The first place that haematopoiesis occurs in the foetus is in the yolk sac. Later on, it occurs in the liver and spleen, which are the major hematopoietic organs from about 6 weeks until 6 – 7 months gestation. At this point, the bone marrow becomes the most important site. Haemopoiesis is restricted to the bone marrow in normal childhood and adult life.

Most vasoconstrictors bind to G-protein coupled receptors. These mediate elevation in intracellular [Ca2+] which leads to vascular smooth muscle contraction. Important vasoconstrictors include noradrenaline, endothelin-1 and angiotensin II.

Increased intracellular Ca2+ is as a result of the release of Ca2+from the sarcoplasmic reticulum and depolarisation and entry of Ca2+via L-type voltage-gated Ca2+channels. Most types of vascular smooth muscle do not generate action potentials – instead, the depolarisation is graded, which allows graded entry of Ca2+.
sequestration by the sarcoplasmic reticulum Ca2+ATPase, removal from the cell by a plasma membrane Ca2+ATPase and Na+/Ca2+exchange decreases intracellular Ca2+, resulting in vasodilation. Relaxation is a result of most endogenous vasodilators when there is an increase in cyclic guanosine monophosphate (cGMP) like nitric oxide) or cyclic adenosine monophosphate (cAMP) like prostacyclin and beta-adrenergic receptor agonists. These activate protein kinases causing substrate level phosphorylation.
Clinically effective vasodilators are L-type Ca2+channel blocker drugs.

Fludrocortisone has the most potent mineralocorticosteroid activity, making it ideal for mineralocorticoid replacement in adrenal insufficiency.

Absolute risk and relative risk are used to assess the strength of a relationship between a disease and a factor that may affect it.

Absolute risk (AR) is the risk of developing a disease over a time period:
AR = the number of events that occur in a group / number of people in that group

The absolute risk reduction (ARR) is the difference between the absolute risk in the control group (ARC) and the absolute risk in the treated group (ART).

ARR = ARC – ART

The control group is the warfarin group, therefore the ARC is 20/500 (0.04).
Treatment group is the ticagrelor group and ART = 30/300 (0.1).

ARR = 0.04 – 0.1 = -0.06. This shows that treatment with ticagrelor increases risk of developing stroke. This is also termed a relative risk increase.

Relative risk, or risk ratio, (RR) is used to compare the risk in the two different groups. It is the ratio of the absolute risks of the disease in the treatment group (ART) to the absolute risk of the disease in the control group (ARC):
RR=ART /ARC

Therefore RR = 0.1 / 0.04 = 2.5
RR < 1 means the intervention reduces the risk of the outcome being studied
RR = 1 means the treatment has no effect on the outcome being studied
RR > 1 means the intervention increased the risk of the outcome being studied
Since RR is 2.5, ticagrelor increases the risk of stroke.

SUMMARY
Absolute risk reduction is -0.06
Absolute risk in warfarin group = 0.04
Relative risk = 2.5
Ticagrelor has no effect on stroke is incorrect because RR is not =1

An ‘average’ person (70 kg male) contains about 40 litres of water in total, separated into different fluid compartments by biological semipermeable membranes; plasma cell membranes between extracellular and intracellular fluid, and capillary walls between interstitial and intravascular fluid. Around two-thirds of the total fluid (27 L) is intracellular fluid (ICF) and one-third of this (13 L) is extracellular fluid (ECF). The ECF can be further divided into intravascular fluid (3.5 L) and interstitial fluid (9.5 L).
Transcellular fluid refers to any fluid that does not contribute to any of the main compartments but which are derived from them e.g. gastrointestinal secretions and cerebrospinal fluid, and has a collective volume of approximately 2 L.
Osmosis is the passive movement of water across a semipermeable membrane from regions of low solute concentration to those of higher solute concentration.

Diabetes insipidus (DI) may result from a deficiency of ADH secretion (cranial DI) or from an inappropriate renal response to ADH (nephrogenic DI). As a result, fluid reabsorption at the kidneys is impaired, resulting in large amounts of hypotonic, dilute urine being passed with a profound unquenchable polydipsia.
The biochemical hallmarks of DI are:
High plasma osmolality (> 295 mOsm/kg)
Low urine osmolality (< 300 mOsm/kg)
Hypernatraemia (> 145 mmol/L)
High urine volume

Flexion of the arm and flexion and supination of the forearm are weakened but not lost entirely due to the actions of the pectoralis major and deltoid, the brachioradialis and the supinator muscles respectively. There is loss of sensation over the lateral aspect of the forearm. Forearm pronation would not be affected as this is primarily produced by the pronator quadratus and pronator teres muscles, innervated by the median nerve.

Insulin is used mainly in type 1 diabetes, where the pancreas makes no insulin and can sometimes be prescribed in type 1 diabetes. There are different types of insulin categorized by their onset of action:

1. Intermediate-acting insulins (isophane insulin NPH):
– intermediate duration of action, designed to mimic the effect of endogenous basal insulin
– starts their action in 1 to 4 hours
– peaks in 4 to 8 hours
– dosing is usually twice a day and helps maintain blood sugar throughout the day
– Isophane insulin is a suspension of insulin with protamine

2. Short-acting insulins (regular insulin)
– starts the action in 30 to 40 minutes
– peaks in 90 to 120 minutes
– duration of action is 6 to 8 hours
– taken before meals, and food is necessary within 30 minutes after its administration to avoid hypoglycaemia

3. Long-acting insulins (glargine, detemir, degludec)
– start action in 1 to 2 hours
– plateau effect over 12 to 24 hours
– Dosing is usually during the night-time after meals. Their long duration of action helps in reducing the frequency of dosing throughout the day.

4. Rapid-acting insulins (lispro, aspart, glulisine)
– start their action in 5 to 15 minutes
– peak in 30 minutes
– The duration of action is 3 to 5 hours
– generally used before meals and always used along with short-acting or long-acting insulins to control sugar levels throughout the day.

The femoral nerve runs down the front of the leg from the pelvis. It gives the front of the thigh and a portion of the lower leg sensation.

Extension of the leg at the knee joint, flexion of the thigh at the hip are produced by muscles that is primarily innervated by the femoral nerve.

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

Hypothyroidism occurs when there is a deficiency of circulating thyroid hormones. It is commoner in women and is most frequently seen in the age over 60.

Iodine deficiency is the commonest cause of hypothyroidism worldwide.

In developed countries, iodine deficiency is not a problem and autoimmune thyroiditis is the commonest cause.

Meckel’s diverticulum is the most prevalent congenital anomaly of the gastrointestinal tract, affecting approximately 2% of the general population. Meckel’s diverticulum are designated true diverticula because their walls contain all the layers found in normal small intestine. Their location varies among individual patients, but they are usually found in the ileum within 100 cm of the ileocecal valve.

Approximately 60% of Meckel’s diverticulum contain heterotopic mucosa, of which over 60% consist of gastric mucosa. Pancreatic acini are the next most common; others include Brunner’s glands, pancreatic islets, colonic mucosa, endometriosis, and hepatobiliary tissues.

A useful, although crude, mnemonic describing Meckel’s diverticulum is the “rule of twos”: 2% prevalence, 2:1 male predominance, location 2 feet proximal to the ileocecal valve in adults, and half of those who are symptomatic are under 2 years of age.

The primary blood supply to the head of the femur is from branches of the medial femoral circumflex artery.

The superior and inferior gluteal arteries supply the hip joint but not the head of femur.

The lateral circumflex artery anastomoses with the medial femoral circumflex artery and assists in supplying the head of femur.

The obturator artery is an important source of blood supply in children up to about 8 years. It gives rise to the artery of the head of femur which runs in the ligamentum teres and is insufficient to supply the head of femur in adults.

Antacids are contraindicated in hypophosphataemia. Liquid preparations are more effective than tablet preparations. Magnesium-containing antacids tend to be laxative whereas aluminium-containing antacids tend to be constipating. Antacids are best taken when symptoms occur or are expected, usually between meals and at bedtime. Antacids should preferably not be taken at the same time as other drugs since they may impair absorption.

Due to their increased risk of cardiovascular adverse events, coxibs and diclofenac are contraindicated in people with ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and mild, moderate, or severe heart failure. Other NSAIDs are only contraindicated in people with severe heart failure. Selective inhibition of COX-2 is associated with less gastrointestinal intolerance. In single doses NSAIDs have analgesic activity comparable to that of paracetamol, therefore given their side effect profile, paracetamol is preferred, particularly in the elderly. Pain relief starts soon after taking the first dose and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3 weeks. Mefenamic acid has only very mild anti-inflammatory properties.

Haemophilia B is a bleeding disorder caused by a deficiency of clotting factor IX. It is the second commonest form of haemophilia, and is rarer than haemophilia A. Haemophilia B tends to be similar to haemophilia A but less severe. The two disorders can only be distinguished by specific coagulation factor assays.

The incidence is one-fifth of that of haemophilia A. Laboratory findings demonstrate prolonged APTT, normal PT and low factor IX.
Haemophilia B inherited in an X-linked recessive fashion, affecting males born to carrier mothers.
There is also a variation called Leyden, in which factor IX levels are below 1% until puberty, when they rise, potentially reaching as high as 40-60% of normal. This is thought to be due to the effects of testosterone at puberty.

Once muscle tissue is damaged, there will be healing via diffuse formation of fibrous tissue, especially due to the widespread ischemia.

Callus formation takes place in the healing of bone, not muscle.

Organised scar formation occurs when a lacerated wound is approximated by sutures so that primary intention wound healing can occur.

Liquefaction degeneration occurs following ischemia in the brain.

Volkmann’s ischemic contracture may occur, but it is not the primary type of healing that will take place but rather the effect of the fibrous scar formation.

Fick’s law tells us that the rate of diffusion of a gas increases:
the larger the surface area involved in gas exchange
the greater the partial pressure gradient across the membrane
the thinner the membrane
the more soluble the gas in the membrane
the lower the molecular weight of the gas

CML is a myeloproliferative disorder characterised by an abnormal pluripotent haemopoietic stem cell. A cytogenetic abnormality known as the Philadelphia chromosome, which results from a reciprocal translocation between the long arms of chromosomes 9 and 22, causes more than 80% of cases of CML.

CML is a disease that develops slowly over several years. This is known as the ‘chronic stage.’ This stage is usually asymptomatic, and 90 percent of patients are diagnosed at this point, with the disease being discovered frequently as a result of a routine blood test. During this stage, the bone marrow contains less than 10% immature white cells (blasts).

When CML cells expand, symptoms typically begin to appear. The ‘accelerated stage’ is what it’s called. Approximately 10% of people are diagnosed at this point. During this stage, between 10% and 30% of blood cells in the bone marrow are blasts. During this stage, common clinical features include:
Fatigue and exhaustion
Night sweats and fever
Distension of the abdomen
Pain in the left upper quadrant (splenic infarction)
Splenomegaly (commonest examination finding)
Hepatomegaly
Bruising is simple.
Gout is a type of arthritis that affects (rapid cell turnover)
Hyperviscosity is a condition in which the viscosity of (CVA, priapism)
A small percentage of patients experience a ‘blast crisis’ (blast stage). More than 30% of the blood cells in the bone marrow are immature blast cells at this stage. Patients with severe constitutional symptoms (fever, weight loss, bone pain), infections, and bleeding diathesis typically present at this stage.

In CML, laboratory findings include:
White cell count is abnormally high (often greater than 100 x 109/l).
Increased number of immature leukocytes causes a left shift.
Anaemia that is mild to moderately normochromic and normocytic.
Platelets can be low, normal, or elevated, and the Philadelphia chromosome can be found in > 80% of patients.
Serum uric acid and ALP levels are frequently elevated.
Tyrosine kinase inhibitors (TKIs), such as imatinib and dasatinib, are the current mainstay of CML treatment.
Allogenic bone marrow transplantation is now only used in cases where TKIs have failed to work.

Decreased blood volume stimulates the secretion of renin (because of decreased renal perfusion pressure) and initiates the renin-angiotensin-aldosterone cascade. Angiotensin-converting enzyme (ACE) inhibitors block the cascade by decreasing the production of angiotensin. Hyperosmolarity stimulates antidiuretic hormone (ADH) [not aldosterone] secretion. Hyperkalaemia, not hypokalaemia, directly stimulates aldosterone secretion by the adrenal cortex. ANP inhibits renin secretion, thereby inhibiting the production of angiotensin and aldosterone.

Atropine is used to treat bradycardia (sinus, atrial, or nodal) or AV block when the patient’s haemodynamic condition is compromised by the bradycardia.

If any of the following adverse features are present, the ALS bradycardia algorithm recommends a dose of atropine 500 mcg IV:
Shock
Syncope
Myocardial ischemia
Insufficiency of the heart

If this does not work, give additional 500 mcg doses at 3-5 minute intervals until a maximum dose of 3 mg is reached. The heart rate can be slowed paradoxically if the dose is higher than 3 mg.

The ALS bradycardia algorithm also suggests the following interim measures:
Transcutaneous pacing
Isoprenaline infusion 5 mcg/min
Adrenaline infusion 2-10 mcg/minutes
Alternative drugs (aminophylline, dopamine, glucagon, glycopyrrolate)

Angiotensin-converting enzyme (ACE) inhibitors are the most common cause of drug-induced angioedema in the United Kingdom and the United States, owing to their widespread use.

Angioedema is caused by ACE inhibitors in 0.1 to 0.7 percent of patients, with data indicating a persistent and relatively constant risk year after year. People of African descent have a five-fold higher chance of contracting the disease.

Swelling of the lips, tongue, or face is the most common symptom, but another symptom is episodic abdominal pain due to intestinal angioedema. Itching and urticaria are noticeably absent.

The mechanism appears to be activated complement or other pro-inflammatory cytokines like prostaglandins and histamine, which cause rapid vasodilation and oedema.

Other medications that are less frequently linked to angioedema include:
Angiotensin-receptor blockers (ARBs)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Bupropion (e.g. Zyban and Wellbutrin)
Beta-lactam antibiotics
Statins
Proton pump inhibitors

The majority of these reactions are minor and can be treated by stopping the drug and prescribing antihistamines.

Intrinsic factor is essential for the absorption of the small amounts of vitamin B12 normally present in the diet from the terminal ileum. The parietal cells of the stomach produce intrinsic factor, and following a gastrectomy, the absorption of vitamin B12 will be markedly reduced, and a deficiency state will exist.

Bacterial infections are common in the following situations:

Platelet transfusions are associated with a higher risk of bacterial infection (as platelets are stored at room temperature)
Immersion in a water bath thawed previously frozen components.
Components of red blood cells that have been stored for several weeks
Gram-positive and Gram-negative bacteria have both been linked to transfusion-transmitted bacterial infection, but Gram-negative bacteria are linked to a higher rate of morbidity and mortality.
Yersinia enterocolitica is the most common bacterial organism linked to transfusion-transmitted bacterial infection. This organism can multiply at low temperatures while also utilising iron as a nutrient. As a result, it’s well-suited to proliferating in blood banks.

The following are some of the most common clinical signs and symptoms of a bacterial infection transmitted through a blood transfusion. These symptoms usually appear shortly after the transfusion begins:
Fever is very high.
Rigours and chills
Vomiting and nausea
Tachycardia
Hypotension
Collapse of the circulatory system

If a bacterial infection from a transfusion is suspected, the transfusion should be stopped right away. Blood cultures and a Gram stain should be requested, as well as broad-spectrum antibiotics. In addition, the blood pack should be returned to the blood bank for an urgent culture and Gram-stain.

Mycobacterium tuberculosis are part of the Mycobacteriaceae family. They are described to have the characteristics of a Gram-positive cell wall but they are not easily stained with Gram stain. This is because their cell wall contains a high lipid content, and this lipid allows the Mycobacteria to bind to alkaline stains with the application and help of heat. Once stained, they are able to resist decolorization even with the use of acid alcohol as the decolourizer, making them very difficult to decolorize, that is why they are known to be acid-fast.

The Ghon complex is a non-pathognomonic radiographic finding on a chest x-ray that is significant for pulmonary infection of tuberculosis. The location of the Ghon’s focus is usually subpleural and predominantly in the upper part of the lower lobe and lower part of the middle or upper lobe.

Skeletal tuberculosis of the spine is referred to as Pott disease.

The risk of reactivation TB is about 3.3% during the first year after a positive PPD skin test and a total of 5% to 15% thereafter in the person’s lifetime. Progression from infection to active disease varies with age and the intensity and duration of exposure. Reactivation TB occurs when there is an alteration or suppression of the cellular immune system in the infected host that favours
replication of the bacilli and progression to disease.