Salbutamol stimulates beta-2 adrenergic receptors, which are the predominant receptors in bronchial smooth muscle (beta-2 receptors are also present in the heart in a concentration between 10% and 50%).

Stimulation of beta-2 receptors leads to the activation of enzyme adenyl cyclase that forms cyclic AMP (adenosine-mono-phosphate) from ATP (adenosine-tri-phosphate). This increase of cyclic AMP relaxes bronchial smooth muscle and decrease airway resistance by lowering intracellular ionic calcium concentrations. Salbutamol relaxes the smooth muscles of airways, from trachea to terminal bronchioles.

Increased cyclic AMP concentrations also inhibits the release of bronchoconstrictor mediators such as histamine and leukotriene from the mast cells in the airway.

Delivery of ubiquitinated substrates to the proteasome.
Ubiquitinated proteins are delivered to the proteasome by various routes and the complete picture of how these pathways fit together has yet to emerge, reviewed in. Some substrates bind directly to the proteasome by interacting with the 19S regulatory particle subunits Rpn1028 or Rpn1329, and probably Rpt530. Alternatively, ubiquitinated substrates can be brought to the proteasome by adaptors that bind both the proteasome and the ubiquitin chain on the substrate to deliver it for degradation.

B-type natriuretic peptide (BNP) is secreted mainly from the left ventricle and it is secreted as a response to stretching caused by increased ventricular blood volume.

Pregnant patient in a third world country with hepatitis: The answer is most likely Hepatitis E. The mortality for Hepatitis E in pregnant women is very high. It is transmitted faecal-orally. There is no hepatitis G. Hepatitis C, B, A are less likely to be the correct answer than E given it’s classic association with pregnancy and poor living conditions.

Melanocytic nevi are benign neoplasms or hamartomas composed of melanocytes. Melanocytes are derived from the neural crest and migrate during embryogenesis to selected ectodermal sites (primarily the skin and the CNS), but also to the eyes and the ears.
They tend to appear during early childhood and during the first 30 years of life. They may change slowly, becoming raised, changing color or gradually fading.. Pregnancy can increase the number of naevi as well as the degree of hyperpigmentation.
They may become malignant and this should be suspected if the naevus increases in size, develops an irregular surface or becomes darker, itches or bleeds.

In a patient with abnormal LFTs and UC, think primary sclerosing cholangitis (PSC). MRCP and liver biopsy is the best answer. MRCP will show classically beads on a string – intra and extrahepatic stricturing and dilation. Remember this finding!! Liver biopsy is required for official diagnosis (need tissue!).

Clozapine can cause neutropenia or agranulocytosis.

Clozapine is an atypical antipsychotic used in the treatment of schizophrenia, and in patients who are intolerant to, or unresponsive to other antipsychotics.

It is a weak D2-receptor and D1-receptor blocking activity, with noradrenolytic, anticholinergic, and antihistaminic properties.

Many antipsychotic drugs can occasionally cause bone marrow depression, but agranulocytosis is particularly associated with clozapine.

Other side effects include:
Hypotension, tachycardia
Fever, sedation, seizures (with high doses)
Appetite increase
Constipation
Heartburn
Weight gain
Extrapyramidal symptoms
Agranulocytosis
Neuroleptic malignant syndrome

11-beta hydroxylase is stimulated by ACTH and responsible for conversion of 11-deoxycortisol to cortisol and deoxycorticosterone to corticosterone.

In 11-beta hydroxylase deficiency, the previously mentioned conversions are partially blocked, leading to:
– Increased levels of ACTH
– Accumulation of 11-deoxycortisol (which has limited biological activity) and deoxycorticosterone (which has mineralocorticoid activity)
– Overproduction of adrenal androgens (DHEA, androstenedione, and testosterone)

The most likely diagnosis is acute atrial fibrillation (AF) precipitated by acute pneumonia. History of fever, cough and the auscultation findings support it. So the most appropriate management is treating the pneumonia with antibiotics. Treating the underlying cause will reduce the heart rate. Other responses are helpful in the management of chronic AF.

Secretin stimulates bicarbonate secretion from the pancreas and liver. VIP induces relaxation of the stomach and gallbladder, secretion of water into pancreatic juice/ bile, and inhibits gastric acid secretion/absorption. CCK classically stimulates gallbladder contraction and relaxation of the sphincter of Oddi. Gastrin stimulates the secretion of HCl by parietal cells in the stomach. Motilin, as the name suggests, increases motility.

Neutrophilia is also commonly associated with polycythaemia vera.

Polycythaemia vera (PV), also known as polycythaemia rubra vera, is a myeloproliferative disorder caused by clonal proliferation of marrow stem cells leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has peak incidence in the sixth decade of life, with typical features including hyperviscosity, pruritus, splenomegaly, haemorrhage (secondary to abnormal platelet function), and plethoric appearance.

Some management options of PV include lose-dose aspirin, venesection (first-line treatment), hydroxyurea (slightly increased risk of secondary leukaemia), and radioactive phosphorus (P-32) therapy.

In PV, thrombotic events are a significant cause of morbidity and mortality. 5–15% of the cases progress to myelofibrosis or AML. The risk of having AML is increased with chemotherapy treatment.

The presence of a third heart sound is the most sensitive indicator of heart failure. All of the other signs can be found in heart failure with varying degrees.

Occupational asthma (OA) could be divided into a nonimmunological, irritant-induced asthma and an immunological, allergy-induced asthma. In addition, allergy-induced asthma can be caused by two different groups of agents: high molecular weight proteins (>5,000 Da) or low molecular weight agents (<5,000 Da), generally chemicals like the isocyanates.
Isocyanates are very reactive chemicals characterized by one or more isocyanate groups (–N=C=O). The main reactions of this chemical group are addition reactions with ethanol, resulting in urethanes, with amines (resulting in urea derivates) and with water. Here, the product is carbamic acid which is not stable and reacts further to amines, releasing free carbon dioxide.

Diisocyanates and polyisocyanates are, together with the largely nontoxic polyol group, the basic building blocks of the polyurethane (PU) chemical industry, where they are used solely or in combination with solvents or additives in the production of adhesives, foams, elastomers, paintings, coatings and other materials.

The complex salts of platinum are one of the most potent respiratory sensitising agents having caused occupational asthma in more than 50% of exposed workers. Substitution of ammonium hexachlor platinate with platinum tetra amine dichloride in the manufacture of catalyst has controlled the problem in the catalyst industry. Ammonium hexachlorplatinate exposure still occurs in the refining process.

Rosin based solder flux fume is produced when soldering. This fume is a top cause of occupational asthma.

Bakeries, flour mills and kitchens where flour dust and additives in the flour are a common cause of occupational asthma.

Cadmium was not found to cause occupational asthma.

In patients with acute renal tubular necrosis, infection in the form of gram-negative septicaemia is the most common cause of death, especially while the patient is awaiting spontaneous recovery of their renal function.

Immune thrombocytopenic purpura (ITP) refers to thrombocytopaenia occurring in the absence of toxic exposure or other diseases associated with low platelets and involves IgG-type antibodies. It is characterised by normal or increased marrow megakaryocytes, shortened platelet survival, and the absence of splenomegaly. Autoimmune haemolytic anaemia (AIHA) occurs commonly in association with ITP. Leukemic transformation, however, does not occur in ITP.

In neonatal ITP, IgG antibodies are passively transferred across the placenta. The infant platelet count may be normal at birth but decreases within 12–24 hours. It is rarely severe enough to induce bleeding diathesis in the infant.

Pneumothorax is defined as air in the pleural space and may be classified as spontaneous, traumatic or iatrogenic. Primary spontaneous pneumothorax occurs in patients without clinically apparent lung disease.
Primary pneumothorax has an incidence of 18-28 per 100,000 per year for men and 1.2-6 per 100,000 per year for women. Most patients present with ipsilateral pleuritic chest pain and acute shortness of breath. Shortness of breath is largely dependent on the size of the pneumothorax and whether there is underlying chronic lung disease.

Young patients may have chest pain only. Most episodes of pneumothorax occur at rest. Symptoms may resolve within 24 hours in patients with primary spontaneous pneumothorax. The diagnosis of a pneumothorax is confirmed by finding a visceral pleural line displaced from the chest wall, without distal lung markings, on a posterior-anterior chest radiograph.

Breathless patients should not be left without intervention regardless of the size of pneumothorax. If there is a rim of air >2cm on the chest X-ray, this should be aspirated.
Aspiration is successful in approximately 70 per cent of patients; the patient may be discharged subsequently. A further attempt at aspiration is recommended if the patient remains symptomatic and a volume of less than 2.5 litres has been aspirated on the first attempt.

If unsuccessful, an intercostal drain is inserted. This may be removed after 24 hours after full re-expansion or cessation of air leak without clamping and discharge may be considered.

An escharotomy is a surgical procedure used to treat full-thickness (third-degree) circumferential burns. In full-thickness burns, both the epidermis and the dermis are destroyed along with sensory nerves in the dermis. The tough leathery tissue remaining after a full-thickness burn has been termed eschar.

Pulmonary alveolar proteinosis (PAP) is a lung condition that is caused by a build-up of proteins and other substances in the alveoli. The alveoli are the part of the lungs that contain air. PAP has the following symptoms:
Shortness of breath, also called dyspnoea
Chest pain or tightness
Fever
Weight loss
Cough (sometimes, but not always)
Low levels of oxygen in the blood
Nail clubbing (abnormal growth of toenails or fingernails)

Serologic studies are generally not useful for PAP. Flexible bronchoscopy with bronchoalveolar lavage (BAL) remains the criterion standard. Elevated levels of the proteins SP-A and SP-D in serum and BAL fluid may be useful. Elevated titer of neutralizing autoantibody against GM-CSF (immunoglobulin G [IgG] isotype) in serum and BAL fluid may be useful. Recent studies have proposed that deficiency of GM-CSF causes pulmonary alveolar proteinosis (PAP); all patients studied had the antibody to GM-CSF. Serum lactate dehydrogenase (LDH) level is usually elevated, but this finding is nonspecific.

High-resolution computed tomography (HRCT) scan of the chest demonstrates areas of patchy ground-glass opacification with smooth interlobular septal thickening and intralobular interstitial thickening, which produces a polygonal pattern referred to as crazy paving.

Light microscopy of the lung parenchymal tissue shows alveoli filled with a granular PAS base-reactive and diastase-resistant eosinophilic material.

Lewy body dementia is an increasingly recognised cause of dementia, accounting for up to 20% of cases. The characteristic pathological feature is alpha-synuclein cytoplasmic inclusions (Lewy bodies) in the substantia nigra, paralimbic and neocortical areas. Neuroleptics should be avoided in Lewy body dementia as patients are extremely sensitive and may develop irreversible parkinsonism. Questions may give a history of a patient who has deteriorated following the introduction of an antipsychotic agent.

An MRI whole spine should be performed in a patient suspected of spinal metastasis which can occur before developing metastatic spinal cord compression. This patient has renal cell carcinoma, which readily metastasises to the bones and also has progressive back pain. He, therefore, needs urgent imaging of his spine before any neurological compromise develops. MRI whole spine is preferable because patients with spinal metastasis often have metastases at multiple levels within the spine. Plain radiographs and CT scans should not be performed as they have a lower sensitivity for revealing lesions and cannot exclude cord compression.

In general, imaging should be performed within one week if symptoms suspicious of spinal metastasis without neurological symptoms are present. If there are symptoms suggestive of malignant spinal cord compression, then imaging should be done within 24 hours.

The signs and symptoms of spinal metastases include:
1. Unrelenting lumbar back pain
2. Thoracic or cervical back pain
3. Pain associated with tenderness and worsens with sneezing, coughing, or straining
4. Nocturnal pain

Because of the patient’s history of excessive alcohol consumption, there is a strong suspicion of alcoholic peripheral neuropathy. In the UK, alcohol abuse and diabetes are the most common causes of peripheral neuropathy.

In myasthenia gravis, repeated muscle contractions lead to reduced muscle strength. The opposite is however classically seen in the related disorder Lambert-Eaton syndrome. Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer, and to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against pre-synaptic voltage gated calcium channel in the peripheral nervous system.

Downbeat nystagmus (DBN) suggests a lesion in the lower part of the medulla. Arnold-Chiari malformation usually presents with symptoms due to brainstem and lower cranial nerve dysfunction such as DBN.

Stopping smoking is the single most effective non-pharmacological intervention which will reduce future ischaemic events. But the rest of the responses are also important interventions with regards to reducing future ischaemic events.

Tetracycline is not recommended in pregnancy because of the risk to fetal development (bones, teeth!). Metronidazole in pregnancy: currently not thought to be an increased risk in pregnancy; however this is not effective against chlamydia. Amoxicillin is shown to be an adequate treatment for chlamydia, so this is the correct answer.

This patient has Klumpke’s paralysis due to damage to the T1 nerve root. This root eventually supplies the median and ulnar nerves. The ulnar nerve supplies all of the intrinsic hand muscles except for those of the thenar eminence and the first and second lumbricals, which are innervated by the median nerve.

Catatonia is a state of apparent unresponsiveness to external stimuli and apparent inability to move normally in a person who is apparently awake. Catatonia can be acute and occur in severely ill patients with underlying psychiatric or other medical disorders.

A history of behavioural responses to others usually includes the presence of the following:
– Mutism (absence of speech)
– Negativism (performing actions contrary to the commands of the examiner)
– Echopraxia (repeating the movements of others)
– Echolalia (repeating the words of others)
– Waxy flexibility (slight, even resistance to positioning by examiner)
– Withdrawal (absence of responses to the environment).

In the presence of a catatonic state, both first and second generation antipsychotics (SGA) may contribute to maintaining or worsening the catatonic state and increase the risk of developing NMS (neuroleptic malignant syndrome).

Electroconvulsive therapy (ECT) is effective in all forms of catatonia, even after pharmacotherapy with benzodiazepines has failed. Response rate ranges from 80% to 100% and results superior to those of any other therapy in psychiatry. ECT should be considered first-line treatment in patients with malignant catatonia, neuroleptic malignant syndrome, delirious mania or severe catatonic excitement, and in general in all catatonic patients that are refractory or partially responsive to benzodiazepines. Early intervention with ECT is encouraged to avoid undue deterioration of the patient’s medical condition.

Electroconvulsive therapy (ECT) is a procedure, done under general anaesthesia, in which small electric currents are passed through the brain, intentionally triggering a brief seizure. ECT seems to cause changes in brain chemistry that can quickly reverse symptoms of certain mental health conditions.

NICE now recommends the three acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) as options for managing mild to moderate Alzheimer’s disease. Memantine is reserved for patients with moderate to severe Alzheimer’s.

Pregnancies affected by T1DM are at increased risk for preterm delivery, preeclampsia, macrosomia, shoulder dystocia, intrauterine fetal demise, fetal growth restriction, cardiac and renal malformations, in addition to rare neural conditions such as sacral agenesis.
Successful management of pregnancy in a T1DM patient begins before conception. Research indicates that the implementation of preconception counselling, emphasizing strict glycaemic control before and throughout pregnancy, reduces the rate of perinatal mortality and malformations.
The 2008 bulletin from the National Institute for Health and Clinical Excellence recommends that preconception counselling be offered to all patients with diabetes. Physicians are advised to guide patients on achieving personalized glycaemic control goals, increasing the frequency of glucose monitoring, reducing their HbA1C levels, and recommend avoiding pregnancy if the said level is > 10%.
Other sources suggest deferring pregnancy until HbA1C levels are > 8%, as this margin is associated with better outcomes.

Poor prognostic factors for breast cancer include:
1. Young age (<40 years)
2. Premenopausal at the time of diagnosis
3. Increased tumour size
4. High-grade tumour
5. Oestrogen and progesterone receptor-negative tumour
6. Positive lymph node status