The patient has paroxysmal nocturnal haemoglobinuria (PNH) complicated by acute hepatic vein thrombosis (Budd–Chiari syndrome).

PNH is an acquired clonal disorder of haematopoietic stem cells, characterised by variable combination of intravascular haemolysis, thrombosis, and bone marrow failure. Diagnosis is made by flow cytometric evaluation of blood, which confirms the CD55 and CD59 deficiencies and deficiency of expression of other GPI-linked proteins. This test is replacing older complement-based assays such as the Ham test and sucrose lysis test.

Silicosis is a common occupational lung disease that is caused by the inhalation of crystalline silica dust. Silica is the most abundant mineral on earth. Workers that are involved for example in construction, mining, or glass production are among the individuals with the highest risk of developing the condition. Acute silicosis causes severe symptoms (e.g., exertional dyspnoea, cough with sputum) and has a very poor prognosis.
Chronic silicosis has a very variable prognosis and affected individuals may remain asymptomatic for several decades. However, radiographic signs are usually seen early on. Typical radiographic findings are calcifications of perihilar lymph nodes, diffuse ground glass opacities, large numbers of rounded, solitary nodules or bigger, confluent opacities. Avoiding further exposure to silica is crucial, especially since the only treatment available is symptomatic (e.g., bronchodilators). Silicosis is associated with an increased risk of tuberculosis and lung cancer. Berylliosis typically affects individuals who are exposed to aerospace industry. Histoplasmosis and tuberculosis do not form eggshell calcifications.

Cyanide poisoning:
Aetiology:
Smoke inhalation, suicidal ingestion, and industrial exposure (specific industrial processes involving cyanide include metal cleaning, reclaiming, or hardening; fumigation; electroplating; and photo processing) are the most frequent sources of cyanide poisoning. Treatment with sodium nitroprusside or long-term consumption of cyanide-containing foods is a possible source.
Cyanide exposure most often occurs via inhalation or ingestion, but liquid cyanide can be absorbed through the skin or eyes. Once absorbed, cyanide enters the blood stream and is distributed rapidly to all organs and tissues in the body. 

Pathophysiology:
Inside cells, cyanide attaches itself to ubiquitous metalloenzymes, rendering them inactive. Its principal toxicity results from inactivation of cytochrome oxidase (at cytochrome a3), thus uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores.

Presentation:
• ‘Classical’ features: brick-red skin, smell of bitter almonds
• Acute: hypoxia, hypotension, headache, confusion
• Chronic: ataxia, peripheral neuropathy, dermatitis

Management:
• Supportive measures: 100% oxygen, ventilatory assistance in the form of intubation if required.
• Definitive: Hydroxocobalamin (iv) is considered the drug of choice and is approved by the FDA for treating known or suspected cyanide poisoning.
• Coadministration of sodium thiosulfate (through a separate line or sequentially) has been suggested to have a synergistic effect on detoxification.
Mechanism of action of hydroxocobalamin:
• Hydroxocobalamin combines with cyanide to form cyanocobalamin (vitamin B-12), which is renally cleared.
• Alternatively, cyanocobalamin may dissociate from cyanide at a slow enough rate to allow for cyanide detoxification by the mitochondrial enzyme rhodanese.

Hypothermia is defined as a core body temperature of < 35 °C.
Hypothermia may produce the following ECG changes:
-Bradyarrhythmia
-Osborne Waves (= J waves)
-Prolonged PR, QRS and QT intervals
-Shivering artefact
-Ventricular ectopics
-Cardiac arrest due to VT, VF or asystole

Rheumatoid arthritis is both common and chronic, with significant consequences for multiple organ systems. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of rheumatoid arthritis, with high specificity, presence early in the disease process, and ability to identify patients who are likely to have severe disease and irreversible damage. However, its sensitivity is low, and a negative result does not exclude disease. Anti-CCP antibodies have not been found at a significant frequency in other diseases to date, and are more specific than rheumatoid factor for detecting rheumatoid arthritis. The other factors that are mentioned do not play a key prognostic role.

Pseudomembranous colitis is caused by a C. difficile infection that causes membranes to form on the colon wall. It is caused most commonly by broad-spectrum antibiotics. This would include cephalosporins, broad-spectrum penicillin, and clindamycin. Macrolides and quinolones have also been reported as potential aetiologies, but much less commonly.

An odds ratio (OR) is a measure of association between an exposure and an outcome. The OR represents the odds that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. Odds ratios are most commonly used in case-control studies, however they can also be used in cross-sectional and cohort study designs as well (with some modifications and/or assumptions). Where

a = Number of exposed cases

b = Number of exposed non-cases

c = Number of unexposed cases

d = Number of unexposed non-cases

OR=(a/c) / (b/d) = ad/bc

The patient’s chronic renal failure causes decreased renal hydroxylation of vitamin D which leads to decreased calcium absorption in the gut. Simultaneously, there is also decreased renal excretion of phosphate, and this combination of factors results in increased PTH levels.

The given history suggests a small fibre painful peripheral sensory neuropathy, the most common cause of which is diabetes. Joint position sense and vibratory sensation are carried through large fibres, and therefore are not currently affected. Sensory nerves are affected more often than motor, so reflexes usually remain in tact.

Vitamin B12 deficiency causes impairment of joint position and vibratory sensation.

Chronic inflammatory demyelinating polyneuropathy (CIPD) causes a large fibre peripheral neuropathy with areflexia.

In syringomyelia there is impaired pain and temperature noted in the upper limbs.

Finally, with alcoholic polyneuropathy, all fibre types are affected (sensory and motor loss). It is usually gradual with long term alcohol abuse and may be accompanied by a nutritional deficiency. In addition, pain is a more dominant feature.

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.

Bicarbonate therapy is not indicated in mild and moderate forms of DKA because metabolic acidosis will correct with insulin therapy. The use of bicarbonate in severe DKA is controversial due to a lack of prospective randomized studies. It is thought that the administration of bicarbonate may actually result in peripheral hypoxemia, worsening of hypokalaemia, paradoxical central nervous system acidosis, cerebral oedema in children and young adults, and an increase in intracellular acidosis. Because severe acidosis is associated with worse clinical outcomes and can lead to impairment in sensorium and deterioration of myocardial contractility, bicarbonate therapy may be indicated if the pH is 6.9 or less.

Three classes of medications are appropriate for the management of major triglyceride elevations: fibric acid derivatives, niacin, and omega-3 fatty acids.

Fibrate is used as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis.

High-dose niacin (vitamin B-3) (1500 or more mg/d) decreases triglyceride levels by at least 40% and can raise HDL cholesterol levels by 40% or more. Niacin also reliably and significantly lowers LDL cholesterol levels, which the other major triglyceride-lowering medications do not.

Omega-3 fatty acids are attractive because of their low risk of major adverse effects or interaction with other medications. At high doses (>4 g/d), triglycerides are reduced.

Bilateral occipital cortex infarction will produce varying degrees of cortical blindness, wherein the patient has no vision but fundoscopy findings are normal. When there are extensive lesions, patients my present with denial of their condition, known as Anton’s Syndrome, and begin to describe objects that they have never seen before.

The patient (known case of acromegaly) seems to have developed cholelithiasis (presenting with right upper quadrant pain) probably due to octreotide.

It is a long-acting analogue of somatostatin which is released from D cells of the pancreas and inhibits the release of growth hormone, glucagon, and insulin.

Uses
– Acute treatment of variceal haemorrhage
– Acromegaly
– Carcinoid syndrome
– Prevent complications following pancreatic surgery
– VIPomas
– Refractory diarrhoea

Adverse effects
Gallstones (secondary to biliary stasis)

Other options:
– Bromocriptine – a dopamine agonist with side effects arising from its stimulation of the brain vomiting centre.
– Desmopressin – predominantly used in patients with diabetes insipidus by increasing the presence of aquaporin channels in the distal collecting duct to increase water reabsorption from the kidneys. The main side effects include headache and facial flushing due to hypertension.
– Metformin – mainly reduces hepatic gluconeogenesis in patients with type 2 diabetes, common side effects include diarrhoea, vomiting, and lactic acidosis
– Levothyroxine – synthetic thyroxine used in patients with hypothyroidism, common side effects result from incorrect dosing and mimic the symptoms of hyperthyroidism.

The patient is most likely to have Bulimia nervosa. A young girl with a low body mass contributes to the low urea. Hypokalaemia and hyponatraemia are due to vomiting. Her urine sodium is also low.
– In Addison’s diseases, there are low levels of sodium and high levels of potassium in the blood. In acute adrenal crisis: The most consistent finding is elevated blood urea nitrogen (BUN) and creatinine. Urinary and sweat sodium also may be elevated.
– In Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) there is hyponatremia with corresponding hypo-osmolality, continued renal excretion of sodium, urine less than maximally dilute and absence of clinical evidence of volume depletion.

The number needed to treat (NNT) is valuable information in treatment decisions. NNT is the inverse of the absolute risk reduction (1/ARR) between two treatment options. Control event rate = 10 / 50 = 0.2
Experimental event rate = 18 / 120 = 0.15

Absolute risk reduction = 0.2 – 0.15 = 0.05
Number needed to treat = 1 / 0.05 = 20

The antithrombotic action of aspirin is due to inhibition of platelet function by acetylation of the platelet cyclooxygenase (COX) at the functionally important amino acid serine529. This prevents the access of the substrate (arachidonic aid) to the catalytic site of the enzyme at tyrosine385 and results in an irreversible inhibition of platelet-dependent thromboxane formation.

Betahistine is a histamine analogue that has been the mainstay treatment drug for Meniere’s disease.

Metabolic acidosis is associated with cocaine overdose.
In overdose, cocaine leads to agitation, tachycardia, hypertension, sweating, hallucinations, and finally convulsions.
Metabolic acidosis, hyperthermia, rhabdomyolysis, and ventricular arrhythmias also occur.
Chronic use may be associated with premature coronary artery disease, dilated cardiomyopathy, and increased risk of cerebral haemorrhage.
There are 3 stages for acute cocaine toxicity:
Stage I: CNS symptoms of headache, vertigo, pseudo hallucinations, hyperthermia, hypertension.
Stage II: increased deep tendon reflexes, tachypnoea, irregular breathing, hypertension.
Stage III: Areflexia, coma, fixed and dilated pupils, hypotension, ventricular fibrillation, apnoea, and respiratory failure.

Treatment:
– Airway, breathing, and circulation to be secured. The patient’s fever should be managed, and one should rule out hypoglycaemia as a cause of the neuropsychiatric symptoms.
– Cardiovascular toxicity and agitation are best-treated first-line with benzodiazepines to decrease CNS sympathetic outflow.
– The mixed beta/alpha blocker labetalol is safe and effective for treating concomitant cocaine-induced hypertension and tachycardia.
– Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil have been shown to reduce hypertension reliably, but not tachycardia.
– Dihydropyridine agents such as nifedipine should be avoided, as reflex tachycardia may occur.
– The alpha-blocker phentolamine has been recommended but only treats alpha-mediated hypertension and not tachycardia.

A grossly elevated APTT may be caused by heparin therapy, haemophilia, or antiphospholipid syndrome. A normal factor VIIIc activity, however, points towards the diagnosis of haemophilia B, which is the deficiency of factor IX in the blood.

Haemophilia is an X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to the deficiency of clotting factor VIII and is more common than haemophilia B, accounting for 90% of the cases. In haemophilia B (Christmas disease), there is a deficiency of clotting factor IX.

Characteristic features of haemophilia include hemarthrosis, haematomas, and prolonged bleeding following trauma or surgery. Coagulation profile of a haemophiliac person shows prolonged bleeding time, activated partial thromboplastin time (APTT), thrombin time (TT), but a normal prothrombin time (PT).

Hypogammaglobulinemia is a complication of chronic lymphocytic leukaemia (CLL) that leads to recurrent infections.

CLL is a type of cancer caused by monoclonal proliferation of well-differentiated lymphocytes, typically B cells (99%). Onset of the disease is usually asymptomatic and later constitutes anorexia, weight loss, bleeding, and recurrent infections. Lymphadenopathy is more marked in CLL than in chronic myelogenous leukaemia (CML).

Investigations to diagnose CLL include blood film and immunophenotyping. Smudge cells (also known as smear cells) seen on the blood film point towards CLL. Complications of the disease include hypogammaglobulinemia leading to recurrent infections, autoimmune haemolytic anaemia in 10–15% of the patients, and transformation to high-grade lymphoma (Richter’s transformation).

Carcinoembryonic antigen (CEA) is a known tumour marker for colorectal cancer. It is not used diagnostically, but in patients with a known diagnosis of colorectal cancer associated with raised CEA levels, it can be used to monitor disease activity and help with the early identification of disease recurrence.

Tumour markers can be divided into:
1. Monoclonal antibodies
CA 125: Ovarian cancer, primary peritoneal cancer
CA 19-9: Pancreatic cancer
CA 15-3: Breast cancer

2. Tumour specific antigens
Prostate specific antigen (PSA): Prostatic carcinoma
Alpha-feto protein (AFP): Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA): Colorectal cancer
S-100: Melanoma, schwannomas
Bombesin: Small cell lung carcinoma, gastric cancer

3. Enzymes
Alkaline phosphatase (ALP)
Neuron specific enolase (NSE)

4. Hormones
Calcitonin
Antidiuretic hormone (ADH)
Human chorionic gonadotropin (hCG)

Glioblastoma multiforme, also considered as grade IV astrocytoma, is the most malignant form of the tumour and accounts for about 20% of all cerebral tumours. These often remain clinically silent until they have reached a large enough size. In adults, glioblastoma multiforme usually occurs in the cerebral hemispheres, especially the frontal and temporal lobes of the brain. About half occupy more than one hemisphere at presentation, and some are multicentric. Biopsy shows high cellularity with mitoses, pleomorphism, and vascular hyperplasia. Prognosis is extremely poor, with only 20% surviving beyond 1 year and 10% beyond 2 years.

When the aim of the randomized controlled trial (RCT) is to show that one treatment is superior to another, a statistical test is employed and the trial (test) is called a superiority trial (test).

Fundoscopy findings of cotton wool spots and retinal tears, accompanied by a history of blurred vision, are characteristic of retinitis. Cytomegalovirus is known to cause retinitis.

Perinatal transmission is the most common cause of Hepatitis B infection worldwide. Post-exposure prophylaxis should be provided, which consists of hepatitis B immune globulin and hepatitis B vaccine within 12 hours of birth. Without this, about 40% will develop chronic infection.

The right and left lung anatomy are similar but asymmetrical. The right lung consists of three lobes: right upper lobe (RUL), right middle lobe (RML), and right lower lobe (RLL). The left lung consists of two lobes: right upper lobe (RUL) and right lower lobe (RLL). The right lobe is divided by an oblique and horizontal fissure, where the horizontal fissure divides the upper and middle lobe, and the oblique fissure divides the middle and lower lobes. In the left lobe there is only an oblique fissure that separates the upper and lower lobe.

The lobes further divide into segments which are associated with specific segmental bronchi. Segmental bronchi are the third-order branches off the second-order branches (lobar bronchi) that come off the main bronchus.

The right lung consists of ten segments. There are three segments in the RUL (apical, anterior and posterior), two in the RML (medial and lateral), and five in the RLL (superior, medial, anterior, lateral, and posterior). The oblique fissure separates the RUL from the RML, and the horizontal fissure separates the RLL from the RML and RUL.

There are eight to nine segments on the left depending on the division of the lobe. In general, there are four segments in the left upper lobe (anterior, apicoposterior, inferior and superior lingula) and four or five in the left lower lobe (lateral, anteromedial, superior and posterior). The medium sized airways offer the maximum airway resistance, not smaller ones.

A fasting blood glucose level from 110 to 126 mg/dL (5.5 to 6.9 mmol/L) is considered prediabetes. This result is sometimes called impaired fasting glucose.
Diabetes mellitus (type 2): diagnosis

The diagnosis of type 2 diabetes mellitus can be made by plasma glucose. If the patient is symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.

Gastrin is released by G cells in the antrum of the stomach. It stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and also aids in gastric motility. It is released in response to the following stimuli: vagal stimulation, antrum distention, hypercalcemia. It is inhibited by the following: presence of acid in stomach, SST, secretion, GIP, VIP, glucagon, calcitonin.