Asthma is a condition characterized by airway hyperresponsiveness, which results in reversible increases in bronchial smooth muscle tone, and variable amounts of inflammation of the bronchial mucosa.
During an acute asthma attack, the already inflamed airways narrow further due to bronchospasm, which leads to increased airway resistance. Because of the increased smooth muscle tone during an asthma attack, the airways also tend to close at abnormally high lung volumes, trapping air behind occluded or narrowed small airways. Thus the acute asthmatic will breathe at high lung volumes, his functional residual capacity will be elevated, and he will inspire close to total lung capacity. The accessory muscles of respiration are often used to maintain the lungs in a hyperinflated state.

During episodes of acute asthma, pulmonary function tests reveal an obstructive pattern. This includes a decrease in the rate of maximal expiratory air flow (a decrease in FEV1 and the FEV1/FVC ratio) due to the increased resistance, and a reduction in forced vital capacity (FVC) correlating with the level of hyperinflation of the lungs. Because these patients breathe at such high lung volumes (near the top of the pressure-volume curve, where lung compliance greatly decreases), they must exert significant effort to create an extremely negative pleural pressure, and consequently fatigue easily. Overinflation also reduces the curvature of the diaphragm, making it less efficient in generating further negative pleural pressure.

The oedema is an effect of the a decreased cardiac output that increases renin release which leads to vasoconstriction and sodium and water retention.

Blurring of vision and dry mouth are antimuscarinic side-effects that are more common with imipramine than other types of tricyclic antidepressants.

Tricyclic antidepressants (TCAs) are used less commonly now for depression due to their side-effects and toxicity in overdose. They are however used widely in the treatment of neuropathic pain, where smaller doses are typically required.

Mechanism of action: Tricyclic antidepressants impose their therapeutic effects by inhibiting presynaptic reuptake of norepinephrine and serotonin in the central nervous system (this, may give rise to seizures).

Common side-effects:
Drowsiness
Dry mouth
Blurred vision
Constipation
Urinary retention

Low-dose amitriptyline is commonly used in the management of neuropathic pain and the prophylaxis of headaches (both tension and migraine).
Lofepramine has a lower incidence of toxicity in overdose
Amitriptyline and dosulepin (dothiepin) are considered the most dangerous in overdose.

Relative Risk = (Probability of event in exposed group) / (Probability of event in not exposed group). The relative risk is mistaken by some, with the odds ratio and absolute risk. Relative risk is the ratio of the probability of an event occurring with an exposure versus the probability of the event occurring without the exposure. Thus to calculate the relative risk, we must know the exposure status of all individuals (either exposed or not exposed). This implies that relative risk is only appropriate for cases where the exposure status and incidence of disease can be accurately determined such as prospective cohort studies.

When you have a patient with HIV and diarrhoea on the exam, think Cryptosporidium. In those who are immunocompetent this organism doesn’t usually cause symptoms, but in immunocompromised people like those with HIV, it causes infection and diarrhoea. Typically those with CD4 counts of <100 cells/µL1 have the greatest risk for prolonged, severe, or extraintestinal cryptosporidiosis.

The patient most likely suffers from antiphospholipid syndrome. The clinical criteria consist of vascular thrombosis and pregnancy morbidity. Vascular thrombosis is defined as one or more clinical episodes of arterial, venous, or small-vessel thrombosis in any tissue or organ confirmed by findings from imaging studies, Doppler studies, or histopathology. ASD, VSDs would cause paradoxical emboli and stroke, however the recurrent pregnancy loss in this case is strongly suggestive of antiphospholipid syndrome. The ECG would be normal in most cases associated with anti phospholipid syndrome.

With biliary obstructive symptoms in a patient with ulcerative colitis, one should immediately think of primary sclerosing cholangitis (PSC). PSC is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic ducts. The best diagnostic test for PSC is ERCP. ANCA antibiotics may be positive, but not the best test to DIAGNOSE THE CONDITION. The same can be said of serum transaminase levels– they will be abnormal but nonspecific. While a liver ultrasound may be helpful, it is not the best test. Liver biopsy would be used to stage the PSC later.

The principal action of organophosphates is the inhibition of acetylcholinesterase’s, therefore leading to the accumulation of acetylcholine at muscarinic receptors (miosis, hypersalivation, sweating, diarrhoea, excessive bronchial secretions), nicotinic receptors (muscle fasciculations and tremor) and in the central nervous system (anxiety, loss of memory, headache, coma).

Removal from the source of the organophosphate, adequate decontamination, supplemental oxygen and atropine are the initial treatment measures. Pralidoxime, an activator of cholinesterase, should be given to all symptomatic patients.

Tacrolimus is a calcineurin inhibitor used as an immunosuppressive agent used for prophylaxis of organ rejection post-transplant.

Pharmacology: Calcineurin inhibition leads to reduced T-lymphocyte signal transduction and IL-2 expression. It has a half-life of 12 hours (average).

Other off-label indications for the use of tacrolimus include Crohn disease, graft-versus-host disease (GVHD), myasthenia gravis, rheumatoid arthritis.

Adverse effects of tacrolimus includes:
Cardiovascular: Angina pectoris, cardiac arrhythmias, hypertension
Central nervous system: Abnormal dreams, headaches, insomnia, tremors.
Dermatologic: Acne vulgaris, alopecia, pruritis, rash
Endocrine and metabolic: Decreased serum bicarbonate, decreased serum iron, new-onset diabetes mellitus after transplant (NODAT), electrolyte disturbances.
Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhoea
Genitourinary: Urinary tract infection
Hepatic: Abnormal hepatic function tests
Neuromuscular and skeletal: Arthralgia, muscle cramps
Ophthalmic: Blurred vision, visual disturbance
Otic: Otalgia, otitis media, tinnitus
Renal: Acute renal failure

Other options:
Sirolimus (a macrolide) is an mTOR inhibitor that blocks the response to IL-2 and has a half-life of 12–15 hours.
Azathioprine inhibits purine synthesis, an essential step in the proliferation of white cells and has a half-life of around 5 hours.

Afferent pupillary defect is simply a delayed pupillary response to light. Accommodation is otherwise unaffected.

Nail dystrophy (pitting of nails, onycholysis, subungual hyperkeratosis), dactylitis, sausage shaped fingers are most commonly seen with psoriatic arthropathy. There is asymmetric joint involvement most commonly distal interphalangeal joints. Uveitis and sacroiliitis may also occur. Arthritis mutilans may occur but is very rare. Cutaneous lesions may or may not develop. When they do, its usually much after the symptoms of arthritis.

Ramipril is an ACE inhibitor that blocks the conversion of angiotensin I to angiotensin II as well as preventing the breakdown of bradykinin, leading to blood vessel dilatation and decreased blood pressure. However, bradykinin also causes smooth muscles in the lungs to contract, so the build-up of bradykinin is thought to cause the dry cough that is a common side-effect in patients that are on ACE inhibitors.

Permanent pacing is not indicated as the bradycardia is reversible. Temporary pacing is the definite treatment. Isoprenaline can be used until temporary pacing is available.

Difficulty in initiating movement (bradykinesia), postural instability and unilateral symptoms (initially) are typical of Parkinson’s. Essential tremor symptoms are usually worse if arms are outstretched and eased by rest and alcohol.

Positive predictive value is the probability that subjects with a positive screening test truly have the disease.

Positive predictive value = true positive / ( true positive + false positive)

Barrett’s oesophagus is the transformation of the normal squamous epithelium of the oesophagus to columnar, intestinal type epithelium. It is often seen in patients with reflux and there is a 50-100 fold increased risk of oesophageal adenocarcinoma in patients with Barrett’s oesophagus.

When closure of the pulmonary valve occurs before the aortic valve, reversed splitting occurs. The causes of reversed splitting are aortic stenosis, hypertrophic cardiomyopathy, left bundle branch block (LBBB), and a ventricular pacemaker.

Oculomotor nerve palsy is an eye condition resulting from damage to the third cranial nerve or a branch thereof. A complete oculomotor nerve palsy will result in a characteristic down and out position in the affected eye. This is because the lateral rectus (innervated by the sixth cranial nerve) and superior oblique (innervated by the fourth cranial or trochlear nerve), is unantagonized by the paralyzed superior rectus, inferior rectus and inferior oblique. The affected individual will also have a ptosis, or drooping of the eyelid, and mydriasis (pupil dilation), not miosis.

People with Systemic Juvenile Idiopathic Arthritis (also known as Stills disease) can have recurrent fevers, a macular rash, joint pain, joint deformities, an enlarged liver and/or spleen, and can occasionally have polyserositis, lung involvement or pericardial effusions. Rheumatoid factor and antinuclear antibodies are usually negative. Treatment is with non-steroidal anti-inflammatory drugs (NSAIDs) and the prognosis is better than for adult rheumatoid arthritis.
In pauciarticular Still’s disease, antinuclear antibodies are present. Large joints are affected and most patients develop classic features of seronegative spondylarthritis.

Thalassaemias are a group of genetic disorders characterised by decreased production of either alpha or beta chains of haemoglobin (Hb). Beta thalassaemia trait is an autosomal recessive condition in which a disproportionate hypochromic, microcytic anaemia occurs—microcytosis is disproportionate to the Hb level. It is usually asymptomatic.

Microcytic anaemia in a female should raise the possibility of either gastrointestinal blood loss or menorrhagia. However, there is no history to suggest this in the aforementioned patient. This, combined with characteristic disproportionate microcytosis and raised HbA2 levels ( >3.5%), point towards beta thalassaemia trait.

Basophilic stippling is also seen in lead poisoning but the raised HbA2 levels cannot be explained in such a case.