The patient presents with worsened renal condition from the last consultation when he was started on enalapril (an ACE inhibitor) so this medication should be stopped. Because there is also no fluid overload; furosemide, a diuretic, should also be stopped.

Azathioprine therapy can cause acute myelosuppression. Toxicity is in part caused by the incorporation of azathioprine-derived 6-thioguanine nucleotides (6-TGN) into deoxyribonucleic acid (DNA). The enzyme thiopurine methyltransferase (TPMT) plays an important role in azathioprine catabolism.

Hydroxychloroquine is used in the management of SLE as it prevents disease progression and has relatively mild side effects, for instance headache, nausea etc. Its use reduces the usage of corticosteroids. It is particularly effective when the disease is less severe and there is no organ involvement. Cyclophosphamide and prednisolone are indicated in cases of renal, neurological and lung involvement.

Thrombotic thrombocytopenic purpura (TTP) is characterised by the von Willebrand factor (vWF) microthrombi within the vessels of multiple organs. In this condition, the ADAMTS13 metalloprotease enzyme which is responsible for the breakdown of vWF multimer, is deficient, causing its build-up and leading to platelet clots that then decreases the circulating platelets, leading to bleeding in the patient.

The most widely used prognostic predictors for acetaminophen over-ingestion is King’s College Criteria, which is: arterial PH < 7.3 after fluid resuscitation, Cr level > 3.4, PT > 1.8x control or > 100s, or INR > 6.5, and Grave III or IV encephalopathy.

The correct answer based on the clinical scenario is Crohn’s disease. Associated with this disease are abscesses and fistulas in the anorectal region, skip lesions, cobble stoning, stricturing, granulomas, and crypt distortion. The other answer choices are not correct. How to rule out ulcerative colitis: it only involves ileocolorectal regions, and this is above that level. You will not see crypt distortion and cobble stoning; it is a more superficial process.

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.

NICE guidelines on hypercalcemia recommend that maintaining good hydration equals drinking 3-4 L of fluid/day, provided there are no contraindications. A low calcium diet is not necessary because intestinal absorption of calcium is reduced. The patient should avoid any other drugs or vitamins that could worsen the hypercalcemia. Mobilization is encouraged and any symptoms of hypercalcemia should be reported.

The major delayed problem with radiotherapy is the development of secondary cancers. This risk begins to appear ten years after therapy.

A prominent A wave is observed in the jugular venous pulse and this indicates the presence of established pulmonary hypertension. In addition the pulmonic component of the second heart sound (P2) may be increased and the P2 may demonstrate fixed or paradoxical splitting. The signs of right ventricular failure include a high-pitched systolic murmur of tricuspid regurgitation, hepatomegaly, a pulsatile liver, ascites, and peripheral oedema.

Minimal change glomerulonephritis usually presents as nephrotic syndrome wherein the patient (usually a young adult) will present with proteinuria, oedema, and impaired kidney function, which were evident in this patient.

An atheroma is an accumulation of degenerative material in the tunica intima (inner layer) of artery walls. The material consists of (mostly) macrophage cells, or debris, containing lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue.

The normal partial pressure reference values are: oxygen PaO2 more than 80 mmHg (11 kPa), and carbon dioxide PaCO2 lesser than 45 mmHg (6.0 kPa).
This patient has an elevated PaCO2 of 6.8kPa which exceeds the normal value of less than 6.0kPa.
The pH is also lower than 7.35 at 7.32

In any patient with asthma, an increasing PaCO2 indicates severe airway obstruction that is leading to respiratory muscle fatigue and patient exhaustion.

According to the British Thoracic Society guidelines:
Indications for admission to intensive care or high-dependency units include
patients requiring ventilatory support and those with acute severe or life-threatening asthma who are failing to respond to therapy, as evidenced by:
• deteriorating PEF
• persisting or worsening hypoxia
• hypercapnia
• arterial blood gas analysis showing fall in pH or rising hydrogen concentration
• exhaustion, feeble respiration
• drowsiness, confusion, altered conscious state
• respiratory arrest

Transfer to ICU accompanied by a doctor prepared to intubate if:
• Deteriorating PEF, worsening or persisting hypoxia, or hypercapnia
• Exhaustion, altered consciousness
• Poor respiratory effort or respiratory arrest

A single dose of intravenous magnesium sulphate is safe and may improve lung function and reduce intubation rates in patients with acute severe asthma. Intravenous magnesium sulphate may also reduce hospital admissions in adults with acute asthma who have had little or no response to standard treatment.

Consider giving a single dose of intravenous magnesium sulphate to
patients with acute severe asthma (PEF <50% best or predicted) who have not had a good initial response to inhaled bronchodilator therapy.
Magnesium sulphate (1.2–2 g IV infusion over 20 minutes) should only be used following consultation with senior medical staff.

High Altitude Cerebral Oedema (HACE) is a severe and potentially fatal manifestation of high altitude illness and is often characterized by ataxia, fatigue, and altered mental status. HACE is often thought of as an extreme form/end-stage of Acute Mountain Sickness (AMS). Although HACE represents the least common form of altitude illness, it may progress rapidly to coma and death as a result of brain herniation within 24 hours, if not promptly diagnosed and treated.

HACE generally occurs after 2 days above 4000m but can occur at lower elevations (2500m) and with faster onset. Some, but not all, individuals will suffer from symptoms of AMS such as headache, insomnia, anorexia, nausea prior to transitioning to HACE. Some may also have concomitant High Altitude Pulmonary Oedema (HAPE). HACE in isolation is rare, but the absence of concomitant HAPE or symptoms of AMS prior to deterioration does not rule-out the presence of HACE.

Most cases develop as a progression of AMS and will include a history of recent ascent to altitude and prior complaints/findings of AMS including a headache, fatigue, nausea, insomnia, and/or light-headedness. Some may also have signs/symptoms of HAPE. Transition to HACE is heralded by signs of encephalopathy including ataxia (usually the earliest clinical finding) and altered mentation which may range from mild to severe. Other symptoms may include a more severe headache, difficulty speaking, lassitude, a decline in the level of consciousness, and/or focal neurological deficits or seizures.

The mainstay of treatment is the immediate descent of at least 1000m or until symptoms improve. If descent is not an option, one may use a portable hyperbaric chamber and/or supplemental oxygen to temporize illness, but this should never replace or delay evaluation/descent when possible. If available, dexamethasone 8mg for one dose, followed by 4mg every 6 hours should be given to adults via PO, IM, or IV routes.
Acetazolamide has proven to be beneficial in only a single clinical study. The suggested dosing regimen for Acetazolamide is 250 mg PO, given twice daily. Though effective in alleviating or temporizing symptoms, none of the adjunct treatment modalities are definitive or a replacement for an immediate descent.

Lofgren’s syndrome is an acute form of sarcoidosis characterized by erythema nodosum, bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. Other symptoms include anterior uveitis, fever, ankle periarthritis, and pulmonary involvement.

Löfgren syndrome is usually an acute disease with an excellent prognosis, typically resolving spontaneously from 6-8 weeks to up to 2 years after onset. Pulmonologists, ophthalmologists, and rheumatologists often define this syndrome differently, describing varying combinations of arthritis, arthralgia, uveitis, erythema nodosum, hilar adenopathy, and/or other clinical findings.

Smoking cessation is the most effective intervention in stopping the progression of COPD, as well as increasing survival and reducing morbidity. This is why smoking cessation should be the top priority in the treatment of COPD. Long term oxygen therapy (LTOT) may increase survival in hypoxic patients. The rest of the options dilate airways, reduce inflammation and thereby improve symptoms but do not necessarily increase survival.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are immediately treated with inhaled beta2 agonists and inhaled anticholinergics, followed by antibiotics (if indicated) and systemic corticosteroids. Methylxanthine therapy may be considered in patients who do not respond to other bronchodilators.
High flow oxygen would worsen his symptoms. Usually titrated oxygen (88 to 92 %) is given in such patients to avoid the risk of hyperoxic hypercarbia in which increasing oxygen saturation in a chronic carbon dioxide retainer can inadvertently lead to respiratory acidosis and death.

Diabetes is a risk factor for hepatocellular carcinoma. Screening has been shown to be effective. Bevacizumab is not used for advanced cases. The incidence is higher in men. Alcohol is not the most common underlying cause worldwide; this is from cirrhosis from diseases like hepatitis B and C.

Myoglobinuria is the condition when there is degeneration of necrosed muscle that it is excreted in the urine. This condition would then cause acute tubular damage leading to renal failure.

The presence of tinnitus, fever and hyperventilation are clues for aspirin (salicylate) toxicity.
Clinical Presentation of salicylate toxicity can include:
• Pulmonary manifestations include: Hyperventilation, hyperpnea, severe dyspnoea due to noncardiogenic pulmonary oedema, fever and dyspnoea due to aspiration pneumonitis
• Auditory symptoms caused by the ototoxicity of salicylate poisoning include: Hard of hearing and deafness, and tinnitus (commonly encountered when serum salicylate concentrations exceed 30 mg/dL).
• Cardiovascular manifestations include: Tachycardia, hypotension, dysrhythmias – E.g., ventricular tachycardia, ventricular fibrillation, multiple premature ventricular contractions, asystole – with severe intoxication, Electrocardiogram (ECG) abnormalities – E.g., U waves, flattened T waves, QT prolongation may reflect hypokalaemia.
• Neurologic manifestations include: CNS depression, with manifestations ranging from somnolence and lethargy to seizures and coma, tremors, blurring of vision, seizures, cerebral oedema – With severe intoxication, encephalopathy
• GI manifestations include: Nausea and vomiting, which are very common with acute toxicity, epigastric pain, GI haemorrhage – More common with chronic intoxication, intestinal perforation, pancreatitis, hepatitis – Generally in chronic toxicity; rare in acute toxicity, Oesophageal strictures – Reported as a very rare delayed complication
• Genitourinary manifestations include: Acute kidney injury (NSAID induced Nephropathy) is an uncommon complication of salicylate toxicity, renal failure may be secondary to multisystem organ failure.
• Hematologic effects may include prolongation of the prothrombin and bleeding times and decreased platelet adhesiveness. Disseminated intravascular coagulation (DIC) may be noted with multisystem organ failure in association with chronic salicylate toxicity.
• Electrolyte imbalances like: Dehydration, hypocalcaemia, acidaemia, Syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypokalaemia
Management of these patients should be done in the following manner:
• Secure Airway, Breathing, and Circulation
• Supportive therapy
• GI decontamination
• Urinary excretion and alkalization
• Haemodialysis

Primary amyloidosis is characterised by abnormal protein build-up in the tissues and organ such as the heart, liver, spleen, kidneys, skin, ligaments, and nerves. However, the most common cause of death in patients with primary amyloidosis is heart failure.

The two statements that fit the characteristics of doxapram are, epilepsy is a contraindication for doxapram use and concurrent use with theophylline may increase agitation.

Doxapram is a central respiratory stimulant. In clinical practice, doxapram is usually used for patients who have an acute exacerbation of chronic obstructive pulmonary disease (COPD) who are unsuitable for admission to the intensive therapy unit for ventilatory support. Doxapram infusion may buy an extra 24 h to allow for recovery.

Contraindications include: ischaemic heart disease, epilepsy, cerebral oedema, acute stroke, asthma, hypertension, hyperthyroidism, and pheochromocytoma.
The infusion may worsen agitation and dyspnoea and lead to hypertension, nausea, vomiting and urinary retention.

Drug interactions:
Concomitant administration of doxapram and aminophylline (theophylline) can cause increased skeletal muscle activity, agitation, and hyperactivity.

The clinical scenario describes a man in liver failure. Given the serological results, he is most likely to have a chronic hepatitis B infection. In chronic hepatitis B infection, you have +HBsAg, +anti-HBc, (-)IgM antiHBc, and (-) anti-HBs. In acute hepatitis B infection, you have +HBsAg, +anti-HBc, +IgM anti-HBc, and negative anti-HBs. in immunity due to natural infection, you have negative HBsAg, +anti-HBc, and + anti-HBs. In immunity due to vaccination, you have negative HBsAg, negative anti-HBc, and positive anti-HBs. While he could have a superimposed hepatitis D infection on top of hepatitis B, there is no mention of hepatitis D serology, make this an incorrect answer. The other choices do not involve hepatitis serologies.

The most likely organism is enterohemorrhagic verotoxin-producing E.coli. It usually causes haemolytic uremic syndrome.
Crohn’s disease rarely manifests in an acute manner.
Polio and giardiasis usually manifest with non-bloody diarrhoea.

This is a picture of bone marrow failure secondary to acute myeloid leukaemia (AML). AML is the acute expansion of the myeloid stem line, which may occur as a primary disease or follow the secondary transformation of a myeloproliferative disorder. It is more common over the age of 45 and is characterized by signs and symptoms largely related to bone marrow failure such as anaemia (pallor, lethargy), frequent infections due to neutropenia (although the total leucocyte count may be very high), thrombocytopaenia (bleeding), ostealgia, and splenomegaly.

The disease has poor prognosis if:
1. Age of the patient >60 years
2. >20% blasts seen after the first course of chemotherapy
3. Chromosomal aberration with deletion of part of chromosome 5 or 7.

Acute promyelocytic leukaemia (APL) is an aggressive form of AML.

Other listed options are ruled out because:
1. Von Willebrand disease: may present with epistaxis and bleeding gums in severe cases but rarely with abnormalities on blood results.

2. Acute lymphoblastic leukaemia: mostly seen in children.

3. Lymphoma: usually presents with rubbery enlargement of lymph nodes.

4. Warfarin overdose: no bilobed large mononuclear cells seen on blood film.

Acute epiglottitis is a life-threatening disorder with serious implications to the anaesthesiologist because of the potential for laryngospasm and irrevocable loss of the airway. There is inflammatory oedema of the arytenoids, aryepiglottic folds and the epiglottis; therefore, supraglottitis may be used instead or preferred to the term acute epiglottitis.

Acute epiglottitis can occur at any age. The responsible organism used to be Hemophilus influenzae type B (Hib), but infection with group A b-haemolytic Streptococci has become more frequent after the widespread use of Hemophilus influenzae vaccination.

The typical presentation in epiglottitis includes acute occurrence of high fever, severe sore throat and difficulty in swallowing with the sitting up and leaning forward position in order to enhance airflow. There is usually drooling because of difficulty and pain on swallowing. Acute epiglottitis usually leads to generalized toxaemia. The most common differential diagnosis is croup and a foreign body in the airway. A late referral to an acute care setting with its serious consequences may result from difficulty in differentiation between acute epiglottitis and less urgent causes of a sore throat, shortness of breath and dysphagia.

The most COMMON site of inflammation from ulcerative colitis is the rectum, making this the correct answer. This is simply a fact you need to memorize. In general, ulcerative colitis only occurs in colorectal regions– nothing in the small bowel (unless there is backwash into the terminal ileum) and nothing further up the GI tract. In Crohn’s it can affect the entire GI tract from mouth to anus.

Pacemaker spikes on the ECG indicate that pacemaker is functioning. The most probable cause for this presentation is the change of the position of the tip of the pacing wire. Increasing the voltage will solve the problem. If it works, repositioning of the pacing wire should be done.

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.

RET (rearranged during transfection) is a receptor tyrosine kinase involved in the development of neural crest derived cell lineages, kidney, and male germ cells. Different human cancers, including papillary and medullary thyroid carcinomas, lung adenocarcinomas, and myeloproliferative disorders display gain-of-function mutations in RET.
In over 90% of cases, MEN2 syndromes are due to germline missense mutations of the RET gene.
Multiple endocrine neoplasias type 2 (MEN2) is an inherited disorder characterized by the development of medullary thyroid cancer (MTC), parathyroid tumours, and pheochromocytoma.