Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults and becomes increasingly common with age, with a median onset of 65 years. It forms only a minor fraction (10 – 15%) of childhood leukaemia. The clinical features of AML typically presents with clinical features secondary to leukaemic infiltration of bone marrow and extramedullary sites:
Anaemia (lethargy, pallor and breathlessness)
Thrombocytopaenia (petechiae, bruising, epistaxis, haemorrhage) – often profound
Neutropenia (infections)
Hepatosplenomegaly
Gingival infiltration
Central nervous system involvement in AML is uncommon.
Leukaemia cutis is the infiltration of neoplastic leukocytes in the skin. It occurs in approximately 10% of patients with AML.Haematological investigations reveal a normochromic normocytic anaemia with thrombocytopenia in most cases. The total white cell count is usually increased and blood film examination typically shows a variable number of blast cells. The bone marrow is hypercellular and typically contains many blast cells.. The prognosis for patients with AML has been improving steadily, particularly for those under 60 years of age, and approximately one-third of patients of this group can expect to achieve long-term cure. For the elderly, the situation is poor and less than 10% of those over 70 years of age achieve long-term remission.
CML is commonly associated with the Philadelphia chromosome. The Philadelphia chromosome is present in only 1% of adults AML cases.
Lymphadenopathy is rare in AML.

Non-Hodgkin’s lymphoma (NHL) refers to a group of lymphoproliferative malignancies (about 85% of B-cell and 15% of T or NK (natural killer) cell origin) with different behavioural patterns and treatment responses. This group of malignancies encompasses all types of lymphoma without Reed-Sternberg cells being present. The Reed-Sternberg cell is classically seen in Hodgkin’s lymphoma.
NHL is five times as common as Hodgkin’s lymphoma. The peak incidence of NHL is in the 50-70 years age group, it affects men and women equally, but affects the Caucasian population more commonly than black and Asian ethnic groups.
The following are recognised risk factors for NHL:
Chromosomal translocations and molecular rearrangements
Epstein-Barr virus infection
Human T-cell leukaemia virus type-1 (HTLV-1)
Hepatitis C
Congenital and acquired immunodeficiency states
Autoimmune disorders, e.g. Sjogren’s syndrome and Hashimoto’s thyroiditis
The most common clinical features at presentation are:
Lymphadenopathy (typically asymmetrical and painless)
Weight loss
Fatigue
Night sweats
Hepatosplenomegaly
For clinical purposes, NHL is divided into three groups: indolent, high-grade, and lymphoblastic.
Indolent (low-grade) NHL:
The cells are relatively mature
Disease follows an indolent course without treatment
Often acceptable to follow a ‘watch and wait’ strategy
Local radiotherapy often effective
Relatively good prognosis with median survival of 10 years
High-grade NHL:
Cells are immature
Disease progresses rapidly without treatment
Significant number of patients can be cured with intensive combination chemotherapy regimens
Approximately 40% cure rate
Lymphoblastic NHL:
Cells are very immature and have a propensity to involve the CNS
Treatment and progression are similar to that of acute lymphoblastic leukaemia (ALL)

Pathogenicity is the ability to cause disease.

Depression of the mandible is generated by the digastric, geniohyoid, mylohyoid and lateral pterygoid muscles on both side, assisted by gravity. The lateral pterygoid muscles are also involved as this movement also involves protraction of the mandible. The masseter muscle is a powerful elevator of the mandible.

Following the action potential, Na+channels remain inactive for a time in a period known as the absolute refractory period where they cannot be opened by any amount of depolarisation. Following this there is a relative refractory period where the temporary hyperpolarisation (due to delayed closure of rectifier K+channels) makes the cell more difficult to depolarise and an action potential can be generated only in response to a larger than normal stimulus. The refractory period limits the frequency at which action potentials can be generated, and ensures that, once initiated, an action potential can travel only in one direction. An action potential is an all or nothing response so the amplitude of the action potential cannot be smaller.

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.

Antinuclear antibodies (ANA) are autoantibodies to the cells’ nucleus.

The ANA test is the most sensitive diagnostic test for verifying the disease’s diagnosis.

Other autoantibodies that may be found in SLE patients include rheumatoid factor, antiphospholipid antibodies, and antimitochondrial antibodies.

Beta thalassemia is caused by mutations in one or both of the beta globin genes. Alpha thalassemia is caused by a deletion or mutation (less commonly) in one or more of the four alpha globin gene copies. β-thalassaemia is more common in the Mediterranean region while α-thalassaemia is more common in the Far East.

According to the CDC definition, a patient co-infected with HIV can be diagnosed with AIDS if he or she has:
A CD4 T-cell count of less than 200 cells/mm3 or;
A CD4 T-cell percentage of total lymphocytes of less than 15% or;
An AIDS defining infection

A Streptococcal throat infection is not an AIDS defining infection.

A normal CD4 count ranges from 500-1000 cells/mm3. A CD4 (not CD8) count of less than 200 cells/mm3 is AIDS defining.

The CD4 count can vary from day to day and depending upon the time that the blood test is taken. It can also be affected by the presence of other infections or illnesses. Treatment with anti-retroviral therapy should be considered at CD4 count of less than 350 cells/mm3.

Serum concentrations of the p24 antigen (the viral protein that makes up most of the core of the HIV) are usually high in the first few weeks after human immunodeficiency virus (HIV) infection and testing for p24 antigen is therefore a useful way of diagnosing very early infection.

Aspirin inhibits cyclo-oxygenase irreversibly by covalently acetylating the cyclo-oxygenase active site in both COX-1 and COX-2. The production of prostaglandin and thromboxane is reduced as a result. As a result, platelet activation and aggregation are reduced. A single dose of aspirin has a half-life of 7-10 days, which is the time it takes for the bone marrow to produce new platelets.

Aspirin only inhibits COX-1, the enzyme that produces thromboxane A2, at low doses (75 mg per day), and thus has a primarily anti-thrombotic effect.

Aspirin inhibits both COX-1 and COX-2 at medium to high doses (500-5000 mg per day). COX-2 is involved in the production of prostaglandins, so it has an anti-inflammatory effect at these concentrations.

Aspirin, when used as an antipyretic for a viral illness in children, can cause Reye’s syndrome. Reye’s syndrome is a potentially fatal liver disease that causes encephalopathy and liver failure.

The inability of aspirin to reduce platelet production of thromboxane A2, and thus platelet activation and aggregation, is known as aspirin resistance. Although the exact frequency and mechanism of aspirin resistance are unknown, it is thought to affect about 1% of users. Women are more likely than men to experience this phenomenon.

According to new research, taking aspirin on a regular basis lowers the risk of colorectal cancer. It may also protect against cancers of the breast, bladder, prostate, and lungs.

Relative risk (RR) is a ratio of the probability of an event occurring in the exposed group versus the probability of the event occurring in the non-exposed group.

RR can be computed as the absolute risk of events in the treatment group (ART), divided by the absolute risk of events in the control group (ARC).

RR = ART/ARC
RR = (30/300) / (20/500)
RR = 2.5

Recall that:

If RR < 1, then the intervention reduces the risk of the outcome.
If RR = 1, then the treatment has no effect on the outcome.
If RR > 1, then the intervention increases the risk of the outcome.

Anti-D is an IgG antibody that targets the antigen Rhesus D (RhD). Plasma from rhesus-negative donors who have been immunised against the anti-D-antigen is used to make anti-D immunoglobulin.

Only RhD negative women are given Anti-D Ig. Women who are RhD negative do not have the RhD antigen on their RBC. If a foetus has the RhD antigen (i.e. is RhD positive) and the mother is exposed to foetal blood, she may develop antibodies to RhD that pass through the placenta and attack foetal red cells (resulting in newborn haemolytic disease). Anti-D is given to bind and neutralise foetal red cells in the maternal circulation before an immune response is triggered. In the event of a sensitising event, 500 IU Anti-D Ig should be administered intramuscularly.

The following are examples of potentially sensitising events:
Birth
Haemorrhage during pregnancy
Miscarriage
Ectopic pregnancy
Death within the womb
Amniocentesis
Chorionic villus sampling
Trauma to the abdomen

The sooner anti-D is given in the event of a sensitising event, the better; however, it is most effective within 72 hours, and the BNF states that it is still likely to have some benefit if given outside of this time frame.

At 28 and 34 weeks, RhD negative women should receive routine antenatal prophylaxis. This is regardless of whether they have previously received Anti-D for a sensitising event during the same pregnancy.

Prophylactic anti-D is not necessary before 12 weeks gestation, as confirmed by scan, in uncomplicated miscarriage (where the uterus is not instrumented), or mild, painless vaginal bleeding, as the risk of foeto-maternal haemorrhage (FMH) is negligible. In cases of therapeutic termination of pregnancy, whether by surgical or medical means, 250 IU of prophylactic anti-D immunoglobulin should be given to confirmed RhD negative women who are not known to be RhD sensitised.

Non-steroidal anti-inflammatory medications (NSAIDs) have slight differences in anti-inflammatory activity, but there is a lot of diversity in individual response and tolerance to these treatments. Approximately 60% of patients will respond to any NSAID; those who do not respond to one may well respond to another. Pain relief begins soon after the first dose, and a full analgesic effect should be achieved within a week, whereas an anti-inflammatory effect may take up to three weeks to achieve (or to be clinically assessable). If the desired results are not reached within these time frames, another NSAID should be attempted.

By inhibiting the enzyme cyclo-oxygenase, NSAIDs limit the generation of prostaglandins. They differ in their selectivity for inhibiting various types of cyclo-oxygenase; selective inhibition of cyclo-oxygenase-2 is linked to reduced gastrointestinal discomfort. Susceptibility to gastrointestinal effects is influenced by a number of different parameters, and an NSAID should be chosen based on the frequency of side effects.
Ibuprofen is an anti-inflammatory, analgesic, and antipyretic propionic acid derivative. Although it has fewer side effects than other non-selective NSAIDs, its anti-inflammatory properties are less effective. For rheumatoid arthritis, daily doses of 1.6 to 2.4 g are required, and it is contraindicated for illnesses characterized by inflammation, such as acute gout.

Because it combines strong efficacy with a low incidence of adverse effects, Naproxen is one of the top choices. It is more likely to cause negative effects than ibuprofen.
Similar to ibuprofen, ketoprofen and diclofenac have anti-inflammatory characteristics, however they have additional negative effects.

Indomethacin has a similar or better effect to naproxen, however it comes with a lot of side effects, such as headaches, dizziness, and gastrointestinal problems.

Common side effects of thiazide diuretics include:
Excessive diuresis, postural hypotension, dehydration, renal impairment
Acid-base and electrolyte imbalance
Hypokalaemia, hyponatraemia, hypomagnesaemia, hypercalcaemia, hypochloraemic alkalosis
Metabolic imbalance
Hyperuricaemia and gout
Impaired glucose tolerance and hyperglycaemia
Altered plasma-lipid concentrations
Mild gastrointestinal disturbances

Tuberculosis is an infection caused by the microorganism Mycobacterium tuberculosis. TB can affect any organ system in the body, but it most commonly affects the lungs, followed by the lymph nodes.

Option Tuberculosis is spread by the faecal-oral route: It is spread by inhalation of droplet nuclei.

There are different methods to diagnose a tuberculosis infection.
1) Direct Microscopy: The organisms are visualised using Ziehl-Neelsen or Auramine staining. This is the quickest method to establish a diagnosis and start treatment.
2) Culture: M. tuberculosis can be grown on Lowenstein-Jensen or Ogawa mediums, but it can take up to 8 weeks; therefore, ZN staining is also performed to start treatment immediately.

Option There are several types of vaccine currently available: The BCG vaccine is the only vaccine approved to prevent TB and is administered at birth.

Option Miliary tuberculosis refers to tuberculosis that affects the spine: Miliary tuberculosis refers to a tuberculosis infection disseminated throughout the body’s organ systems via the blood or lymphatics. Pott’s disease is extrapulmonary TB that affects the spine. It usually affects the lower thoracic and upper lumbar regions.

Option A Ghon focus typically appears at the apex of a lung: The Ghon focus is a primary sign of TB that forms in the lung of previously unaffected patients. It typically occurs in the mid or lower zones of the lung.

Factors increasing compliance:
Old age
Emphysema

Factors decreasing compliance:
Pulmonary fibrosis
Pulmonary oedema
Atelectasis
Extremes of lung volumes (at higher lung volumes the compliance of the lung becomes less as the lung becomes stiffer)

Pancreatic exocrine secretion is controlled by:
Parasympathetic stimulation which enhances secretion of both the enzyme and aqueous components
Sympathetic stimulation which inhibits pancreatic secretion
Secretin which stimulates secretion of the alkaline-rich fluid from ductal cells
Cholecystokinin which stimulates secretion of the enzyme-rich fluid from acinar cellsSomatostatin which inhibits secretion from both acinar and ductal cells
Gastrin which stimulates pancreatic acinar cells to secrete digestive enzymes

Hyperacusis is increased acuity of hearing with hypersensitivity to low tones resulting from paralysis of the stapedius muscle, innervated by the facial nerve. General sensation to the face and to the anterior two-thirds of the tongue is carried by the divisions of the trigeminal nerve (although taste to the anterior two-thirds of the tongue is supplied by the facial nerve). Eye movements are mediated by the oculomotor, trochlear and abducens nerve. Ptosis results from paralysis of the levator palpebrae superioris, innervated by the oculomotor nerve, or the superior tarsal muscle, innervated by the sympathetic chain.

Cyclizine is a piperazine derivative that functions as an antihistamine (H1-receptor antagonist). To prevent nausea and vomiting, it is thought to act on the chemoreceptor trigger zone (CTZ) and the labyrinthine apparatus. It has a lower antimuscarinic effect as well.

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.

A diagnosis of AIDS can be made in a patient infected with HIV if the patient has a CD4 count < 200 cells/uL, or an AIDS-defining illness. Antiretroviral treatment should be considered in patients with CD4 counts < 350 cells/uL.

Oral candidiasis is not an AIDS defining illness – candidiasis of the bronchi, trachea, lungs or of the oesophagus is an AIDS defining illness.

A positive p24 antigen test seen in early HIV infection and does not indicate the development of AIDS.

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.

The iliacus flexes the thigh at the hip joint when the trunk is stabilised. It flexes the trunk against gravity when the body is supine.

The meningococcus is solely a human pathogen, and up to 50% of the population may carry meningococci in the nasopharynx. Factors that lead to invasion and production of disease include complex inter-relationships of genetic predisposition, host status, environmental conditions, and virulence of the organism.

Meningococcal disease is the most common infectious cause of death in childhood in developed countries. It presents as septicaemia, meningitis, or a combination. Septicaemia is the more dangerous presentation, especially with septic shock; meningitis is more likely to lead to neurodevelopmental sequelae. Classic features of septicaemia are a non-blanching rash in a feverish, ill child.

Cephalosporins of the first generation  include cephalexin, cefradine, and cefadroxil. Urinary tract infections, respiratory tract infections, otitis media, and skin and soft-tissue infections are all treated with them.

Second-generation cephalosporins include cefuroxime, cefaclor, and cefoxitin. These cephalosporins are less vulnerable to beta-lactamase inactivation than the ‘first-generation’ cephalosporins. As a result, they’re effective against germs that are resistant to other antibiotics, and they’re especially effective against Haemophilus influenzae.

Cephalosporins of the third generation include cefotaxime, ceftazidime, and ceftriaxone. They are more effective against Gram-negative bacteria than second generation’ cephalosporins. They are, however, less effective against Gram-positive bacteria such Staphylococcus aureus than second-generation cephalosporins.

An intention tremor is characteristic of cerebellar dysfunction. Resting tremor may be seen in Parkinsonism.

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 (the presence of fatty acids and monoglycerides in the duodenum inhibits gastric emptying). 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. Pancreatic lipase digests triglyceride into monoglycerides and free fatty acids. The products of fat digestion (fatty acids and monoglycerides), cholesterol and fat-soluble vitamins diffuse passively into the enterocytes. Once inside the epithelial cell, lipid is taken into the smooth endoplasmic reticulum where much of it is re esterified. Dietary and synthesised lipids are then incorporated into chylomicrons in the Golgi body, which are exocytosed from the basolateral membrane to enter lacteals.

Inguinal hernias can present with an array of different symptoms. Most patients present with a bulge in the groin area, or pain in the groin. Some will describe the pain or bulge that gets worse with physical activity or coughing. Symptoms may include a burning or pinching sensation in the groin. These sensations can radiate into the scrotum or down the leg. It is important to perform a thorough physical and history to rule out other causes of groin pain. At times an inguinal hernia can present with severe pain or obstructive symptoms caused by incarceration or strangulation of the hernia sac contents. A proper physical exam is essential in the diagnosis of an inguinal hernia. Physical examination is the best way to diagnose a hernia. The exam is best performed with the patient standing. Visual inspection of the inguinal area is conducted first to rule out obvious bulges or asymmetry in groin or scrotum. Next, the examiner palpates over the groin and scrotum to detect the presence of a hernia. The palpation of the inguinal canal is completed last. The examiner palpates through the scrotum and towards the external inguinal ring. The patient is then instructed to cough or perform a Valsalva manoeuvre. If a hernia is present, the examiner will be able to palpate a bulge that moves in and out as the patient increases intra abdominal pressure through coughing or Valsalva.

Groin hernias are categorized into 2 main categories: inguinal and femoral.

Inguinal hernias are further subdivided into direct and indirect. An indirect hernia occurs when abdominal contents protrude through the internal inguinal ring and into the inguinal canal. This occurs lateral to the inferior epigastric vessels. The hernia contents may extend into the scrotum, and can be reduced superiorly then superolaterally. A direct inguinal hernia is protrusion of abdominal contents through the transversalis fascia within Hesselbach’s triangle. The borders of Hesselbach’s triangle are the inferior epigastric vessels superolaterally, the rectus sheath medially, and inguinal ligament inferiorly.

A femoral hernia is a protrusion into the femoral ring. The borders of the femoral ring are the femoral vein laterally, Cooper’s ligament posteriorly, the iliopubic tract/inguinal ligament anteriorly and lacunar ligament medially.

The most potent diuretics are loop diuretics e.g. furosemide. They work by inhibiting the Na+/K+/2Cl-symporter in the thick ascending limb of the loop of Henle, which inhibits sodium, potassium, and chloride reabsorption. As a result, there is diuresis with loss of these electrolytes. There is a reduction in transcellular voltage difference, paracellular calcium and magnesium reabsorption.
The medullary interstitium becomes more concentrated by salt reabsorption in the ascending limb. Loop diuretics block this process and reduce the ability of the kidney to concentrate urine. In the collecting duct, there is increased sodium delivery to the principal cells, which increases potassium secretion in return for sodium reabsorption.

The volume of air that remains in the lungs after a single breath is known as functional residual capacity (FRC). It is calculated by combining the expiratory reserve volume and residual volume. In a 70 kg, average-sized male, a normal functional residual capacity is approximately 2100 mL.