Mistakes Flashcards

Question

Gene mutations in haemochromatosis

Answer 1

Most common: C282Y, H63D ## Footnote The mutations associated with haemocromatosis result in increased iron absorption despite the existence of excessive iron stores; this results in the accumulation of iron in different organs of the body, and particularly in the liver.

Answer 2

Decreased plasma hepcidin ## Footnote The C282Y mutation found in haemochromatosis leads to reduced hepcidin expression, which drives excessive iron accumulation. C282Y is part of the genetic code for the HFE protein, and the mutation impairs the ability of HFE to bind beta-2 microglobulin. Normally, HFE is present on the cell surface, and this impaired binding to beta-2 microglobulin causes HFE to aggregate in the intracellular space. Because it can't reach the cell surface, signalling about the level of iron stores is impaired, and this drives excess iron accumulation.

Answer 3

hereditary tyrosinaemia. ## Footnote The enzyme is the last enzyme in the degradation pathway of tyrosine. It is accumulation of another metabolite (succinyl acetone) in the pathway that leads to progressive liver disease, renal tubular dysfunction and porphyria-like crises. Patients experience a dramatic improvement in prognosis following treatment with nitisinone. Nitisinone blocks the formation of maleylacetoacetic acid and fumarylacetoacetic acid, precursors to succinyl acetone.

Answer 4

serum IgM anti-delta + IgG anti-HBc ## Footnote Hepatitis D (delta) viral infection is well recognised to occur as a superinfection in patients who are chronically infected with hepatitis B. Superinfection results in an acute flare-up of a previously quiescent chronic HBV infection. The presence of serum IgM anti-delta at the same time as IgG anti-HBc confirms the diagnosis.

Answer 5

Azathioprine (or its metabolite mercaptopurine) should be started if a patient has more than **one relapse requiring corticosteroids in the last 12 months**. ## Footnote The general approach is to withdraw azathioprine after 5 years of therapy, depending on the course of the disease. Azathioprine is associated with an approximately 4-fold increased risk of developing lymphoma.

Answer 6

Staphylococcal food poisoning leads to profuse vomiting that occurs 2-4 hours after eating food (often pre-made salads, meat or dairy products) that is contaminated by an enterotoxin. Diarrhoea occurs a few hours later and is profuse and watery.

Answer 7

HBsAg ## Footnote It typically becomes detectable approximately 4 weeks after exposure to the virus. The presence of HBsAg indicates an active hepatitis B infection, making it the earliest and most reliable marker for acute infection. Detecting HBsAg early allows for prompt medical intervention and monitoring, which is crucial for managing potential complications in the nurse.

Answer 8

Marked cholestasis

Answer 9

2 or more of 3 urine collections must show that urinary cortisol excretion is greater than 3x ULN ## Footnote An alternative where patients find it difficult to comply with urine collection is the **overnight low dose dexamethasone suppression test**, in which Cushing's is excluded by plasma cortisol < 60 mol/l.

Answer 10

Used to differentiate between pituitary dependent and ectopic Cushing's (in combination with ACTH levels)

Answer 11

**Low**: cortisol **High**: adrenal sex steroids, most notably DHEA. | Non-classical CAH caused by a deficiency in the enzyme11ß-hydroxylase re

Answer 12

Spontaneous abortions e.g. miscarriage (3x higher risk), preterm delivery | Levothyroxine can attenuate the risks

Answer 13

IV cephalosporins and oral fluoroquinolones have shown a significant short-term survival improvement. ## Footnote This leads to one life saved in every 22 patients treated and an infection evented in every four patients. Twenty per cent of variceal bleed patients exhibit signs of infection within 48 hours of admission.

Answer 14

autosomal dominant manner ## Footnote Caused by a mutation in the STK11/LKB1 gene (the serine/threonine kinase 11 gene) in most cases.

Answer 15

Gastrointestinal luminal peptides Also: stomach distension, vagal stimulation and hypercalcaemia.

Answer 16

G-cells in the duodenum and the pyloric antrum of the stomach

Answer 17

HBV DNA ## Footnote HBV DNA titres may be high even if HBeAg (the traditional serological marker of high infectivity) is negative, because the patient may be infected with a hepatitis B 'pre core' mutant that does not produce HBeAg but which may cause severe disease.

Answer 18

presumed as a result of the production of lithogenic bile

Answer 19

The upper lip ## Footnote The cavernous sinuses lie on either side of the body of the sphenoid and receive venous blood from the facial veins (via the superior and inferior ophthalmic veins), and the sphenoid and the middle cerebral veins. The anterior facial vein drains the face and upper lip - hence the danger of spread of infection from this locus.

Answer 20

The posterior portion of the interventricular septum and the posterior left ventricular wall ## Footnote The right coronary artery arises from the right coronary sinus, giving off branches supplying the right atrium and right ventricle. The right coronary artery then continues as the posterior descending coronary artery, which supplies the posterior portion of the interventricular septum and the posterior left ventricular wall. However, there is anatomical variability with where the PDA arises.

Answer 21

Right upper zone ## Footnote An azygous lobe is seen in about 0.5% of routine chest radiographs and is a normal variant. It is seen as a 'reverse comma sign' behind the medial end of the right clavicle.

Answer 22

Anti-cyclic citrullinated peptide antibodies

Answer 23

Can occur as the VIll cranial nerve becomes compressed due to bony overgrowth causing neural foraminal narrowing.

Answer 24

Microscopic polyangiitis ## Footnote Approximately 90% of patients have glomerulonephritis. Renal involvement is equally common in granulomatosis with polyangiitis, and 80% of patients will go on to have glomerulonephritis.

Answer 25

Impaired renal excretion of uric acid (90% of patients) ## Footnote Increased production of uric acid (only 10%)

Answer 26

Anterior ischaemic optic neuropathy ## Footnote Visual manifestations, which include blurred vision, amaurosis fugax, transient and permanent blindness, diplopia and visual hallucinations, are caused by ischaemic changes in the ciliary arteries, causing anterior ischaemic optic neuropathy.

Answer 27

Desmopressin (DDAVP) ## Footnote This should be combined with tranexamic acid, an inhibitor of fibrinolysis.

Answer 28

Fatigue ## Footnote Fatigue can be very debilitating in myelofibrosis, and these patients are often very catabolic. Splenomegaly can often cause problems with food intake, due to compression on the stomach. In addition, anaemia will also contribute to the fatigue.

Answer 29

False positive VDRL testing is a common feature in patients with APA syndrome.

Answer 30

Prolonged PT is usually seen in patients with liver disease leading to failure of synthesis of vitamin K dependent clotting factors, rather than due to APA syndrome.

Answer 31

Perilesional skin biopsy for examination by direct immunofluorescence ## Footnote The lesions develop at the subepithelial layer (hence the tense appearance - unlike the more superficial blisters of pemphigus that slough off). Direct immunofluorescence studies are considered the gold standard for the diagnosis of pemphigoid, detecting immunoglobulin binding and complement deposits within the tissue.

Answer 32

Co-oximetry ## Footnote Co-oximetry is the best test for diagnosing methaemoglobinaemia because it can directly measure methaemoglobin levels in the blood. Methaemoglobinaemia occurs when the iron in haemoglobin is oxidised from ferrous (Fe2+) to ferric (Fe3+), impairing its ability to bind and release oxygen efficiently. This condition results in functional anaemia and cyanosis despite normal partial pressure of oxygen and pulse oximetry readings, as seen in this patient's presentation. Co-oximetry differentiates between various haemoglobin species, providing a precise measurement necessary for an accurate diagnosis.

Answer 33

Cutaneous T-cell lymphoma ## Footnote It is an indolent lymphoma of mature T-cells predominantly involving the skin. The patient may have circulating abnormal T-cells called Sézary cells. If this is associated with erythroderma, they are said to have the Sézary syndrome. They can present with severe pruritus and psoriasis-like lesions. Ultimately deeper organs are affected, particularly lymph nodes, spleen, liver and bone marrow. Chemotherapy may be needed.

Answer 34

All-trans retinoic acid (ATRA) ## Footnote All-trans retinoic acid (ATRA) causes immature promyelocytes to mature, alleviating the symptoms of DIC. It is usually combined with an anthracycline (daunorubicin or idarubicin).

Answer 35

Reduced levels of NADPH ## Footnote G6PD plays a vital role in the hexose monophosphate pathway. It is involved in the oxidation of glucose 6-phosphate to 6-phosphoglycerate; this oxidation reaction is needed in red blood cells as it provides the only source of NADPH. NADPH, in conjunction with glutathione, protects the red blood cell from oxidative stress. An extensive range of drugs may cause acute haemolysis in G6PD deficiency, these include aspirin, antimalarials, antibacterials (including ciprofloxacin and sulphonamides), and other drugs such as vitamin K, probenecid and quinidine. Acute infection may also exacerbate the risk of haemolysis.

Answer 36

Upper gastrointestinal tract ## Footnote The stomach is the most common site of primary gastrointestinal lymphoma, followed by the small intestine. Oesophageal and primary colorectal lymphomas are rare.

Answer 37

Medial ## Footnote The point tenderness over the medial epicondyle and pain on pronation and flexion of the wrist confirm the diagnosis. Treatment with NSAIDS and physiotherapy is the mainstay of therapy, and he should of course be advised to stop golf for a while. Medial tendon release may be of value in patients who fail to respond to conservative management.

Answer 38

IV flumazenil ## Footnote However, there is a risk of seizures, especially in patients concurrently receiving tricyclic antidepressants.

Answer 39

IV sodium bicarbonate ## Footnote Indications for sodium bicarbonate in tricyclic overdose include significant acidosis, reduced conscious level and a QRS greater than 100 ms. These indicate a high risk of seizures and ventricular arrhythmia, which can be minimised by treatment with intravenous sodium bicarbonate. Prolongation of the QRS duration provides an indicator of sodium channel blockade and arrhythmia risk; if QRS duration is > 160 ms the risk of arrhythmia is > 50%.

Answer 40

Dubin-Johnson syndrome (DJS) is a rare, inherited disorder that affects the liver’s ability to process and excrete bilirubin, leading to a chronic but benign form of jaundice (yellowing of the skin and eyes). ## Footnote Dubin-Johnson syndrome is inherited with an autosomal recessive pattern, and is seen more frequently in patients of Jewish heritage. In most patients the jaundice is asymptomatic and remains at a low level, with no long-term sequelae. Bilirubin is conjugated and appears in the urine. Coproporphyrin excretion pattern can be used to confirm the diagnosis.

Answer 41

Relative risk (RR) = (incidence among exposed)/(incidence among unexposed)

Answer 42

Green or blue urine is associated with pseudomonal urinary tract infection, and it is also associated with use of a number of medications including: Amitriptyline, indigo carmine, IV cimetidine, IV promethazine, methylthioninium chloride and triamterene.

Answer 43

Phenothiazines, phenazopyridine, rifampicin and hydroxocobalamin

Answer 44

Metronidazole, nitrofurantoin, some antimalarial agents, fava beans. ## Footnote Senna is associated with brown/black urinary discoloration.

Answer 45

In the nucleus ## Footnote For nuclear-encoded genes, RNA splicing takes place within the nucleus itself. Splicing is catalysed by spliceosomes, which are composed of five small nuclear RNAs (snRNAs) and associated proteins, and leads to the removal of introns and joining together of exons. Alternative splicing is believed to drive genetic diversity in eukaryotes. It is thought that around 20 000 splice variants exist in humans.

Answer 46

T1 nerve root ## Footnote Global wasting of the hand is a result of wasting of the intrinsic muscles of the hand and indicates damage to both the median and the ulnar nerves, with damage to the T1 nerve root. The T1 root supplies the intrinsic muscles of the hand.

Answer 47

Amyloidosis ## Footnote Amyloidosis is not a single disorder, rather a group of disorders that produce a protein with a particular pattern that then aggregates within the organs. Amyloid protein is made up of non-branching fibrils arranged in B-pleated sheets; the protein is insoluble and resistant to breakdown and so accumulates in any organ. If it accumulates in the heart, it causes amyloid heart disease, which has a very poor prognosis.

Answer 48

Pompe disease, also known as Glycogen Storage Disease Type II, is a rare, inherited metabolic disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). Pompe disease is characterised by cardiomyopathy, rapid onset of muscle hypotonia, weakness, glossomegaly, normal cerebral development. Death is common in the first year of life.

Answer 49

Carbamazepine ## Footnote The initial dose is 100 mg up to twice daily and can be titrated up every two weeks until symptoms are resolved - maximum dose is 1600 mg in divided does daily. Specialist referral will be required in cases of uncontrolled pain despite optimal treatment or intolerance to carbamazepine. Surgery is a treatment option where there is compression of the trigeminal nerve identified on MRI.

Answer 50

Botulinum toxin injection ## Footnote Secondary causes need to be excluded such as drugs (neuroleptics) and cervical spine abnormalities. If a primary cervical dystonia is diagnosed botulinum toxin is the drug of choice. Botulinum toxin injections are useful in spasticity and hemifacial spasms.

Answer 51

Pyridostigmine 30 mg four times daily (QDS) PO for 2-4 days

Answer 52

Propranolol ## Footnote Primidone is a suitable alternative for those who cannot take propranolol or for whom it is ineffective.

Answer 53

Ipsilateral hyperreflexia below the level of the lesion ## Footnote Spinal cord hemisection, also known as the Brown-Séquard syndrome (BSS), is associated with symptoms affecting dorsal columns, spinothalamic tract and corticospinal tract. There is ipsilateral paralysis, loss of vibration and position sense, and hyperreflexia below the level of the lesion. Contralateral loss of pain and temperature sensation, usually beginning about two to three segments below the level of the lesion, is also seen. In the clinical situation, a mix of these signs is usually seen as hemisection is rarely complete.

Answer 54

This causes the classic combination of an evolving spastic paraparesis (long tract signs), peripheral neuropathy (absent ankle jerks) and a posterior column pattern of sensory loss (vibration and joint-position sense). The MRI typically shows increased signal on T2-weighted imaging, predominantly in the dorsal columns.

Answer 55

viral meningitis ## Footnote The other aetiologies typically cause a low (bacterial) or very low (tuberculous, fungal) CSt/blood glucose ratio (ie CS- glucose < 40% of blood glucose). Enteroviruses (including echovirus and coxsackie) are the most common cause of viral meningitis in the UK.

Answer 56

Increased signal in the pulvinar of the thalamus ## Footnote The clinical picture given is typical of variant Creutzfeldt-Jakob disease (vCJD), the human form of bovine spongiform encephalopathy. This is a rare condition with a median age of onset of 28 years. Typical symptoms include persistent painful sensory symptoms and neuropsychiatricdisturbance followed by a rapidly progressive dementia with ataxia, myoclonus and sometimes dystonia. A definitive diagnosis requires postmortem tissue confirmation, but some investigations allow categorisation into 'possible' or 'probable cases. MRI scanning is usually the first step. The 'pulvinar sign' on cranial MRI has been found in > 90% of pathologically confirmed cases of vCJD (but not sporadic or other forms) so it is the correct answer here.

Answer 57

Acid phosphatase ## Footnote Minor elevations of liver enzymes are common in Gaucher's disease, but it is acid phosphatase and angiotensin-converting enzyme that are most commonly raised in the serum. Gaucher's disease is the most common lysosomal storage disease; it is caused by deficient activity of acid beta-glucosidase, leading to the deposition of glucocerebroside in cells of the macrophage-monocyte system. It is classified into three subtypes, non-neuropathic, acute neuropathic and chronic neuropathic. Recombinant glucosidase and glucosylceramide inhibitors (e.g. miglustat) are the mainstay of therapy.

Answer 58

Hypomagnesaemia ## Footnote Patients with ileostomies can lose large amounts of magnesium through their stomas; hypomagnesaemia impairs PTH secretion and can cause hypocalcaemia that is resistant to an increased provision of calcium. In this situation it's important not only to replace calcium, but also to replace magnesium salts

Answer 59

No growth - reactive arthritis is a sterile arthritis and an organism is not isolated from the joint aspirate. ## Footnote Reactive arthritis is not a septic arthritis — it's a sterile inflammatory arthritis that occurs after an infection (usually GU or GI), due to an immune-mediated reaction, not direct joint infection. The original infection (e.g., Chlamydia, Salmonella) is often resolved or located elsewhere (e.g., urethra, gut), and the organisms are not present in the joint.

Answer 60

Denosumab ## Footnote This is given as a 60 mg subcutaneous injection every six months. It is contraindicated in hypocalcaemia and hypophosphataemia. Denosumab is a monoclonal antibody that targets the RANK ligand. Common side-effects are joint and muscle pains.

Answer 61

The Milwaukee shoulder is a severe erosive osteoarthritis of the shoulder with a haemorrhagic (bloody) effusion, usually seen in elderly ladies.

Answer 62

Inflammation or degeneration (tendinopathy) of the supraspinatus tendon Often results from overuse, impingement, or minor trauma May lead to rotator cuff syndrome or impingement syndrome

Answer 63

Anticonvulsants such as phenytoin and phenobarbital can induce liver enzymes that lead to an increased breakdown of 25-hydroxycholecalciferol, and this causes osteomalacia. The X-ray shows evidence of the Looser's zones (pseudofractures), which are typical of osteomalacia.

Answer 64

The presentation suggests IgA nephropathy (Berger’s disease), which often causes visible haematuria following respiratory infections. Renal biopsy is required to confirm the diagnosis: * Light microscopy: mesangial proliferation * Immunostaining: IgA deposits in the mesangium

Answer 65

Polyarteritis nodosa (PAN)

Answer 66

Marked vascular proliferation of the synovial membrane ## Footnote This reflects the chronic inflammatory process underlying the disease. The synovium becomes hyperplastic and infiltrated by lymphocytes and plasma cells, forming an invasive tissue known as pannus. Over time, this proliferative synovium contributes to cartilage destruction, joint erosion, and the progression of the disease.

Answer 67

Osteoarthritis

Answer 68

Presence of acute kidney injury (AKI) – associated with a poorer prognosis, reflecting severe renal involvement.

Answer 69

IV procyclidine ## Footnote IV procyclidine will produce a rapid clinical response, usually within 20-30 min. Oculogyric crises are a form of acute dystonia, and may be caused by anti-psychotics and certain anti-emetics, including metoclopramide and prochlorperazine.

Answer 70

Malignant pleural effusion ## Footnote The presence of a malignant pleural effusion indicates pleural involvement, which signifies stage IV (M1a) disease in lung cancer staging. This finding typically precludes surgical resection, as it reflects metastatic spread and is associated with a poor prognosis.

Answer 71

Pulmonary eosinophilia

Answer 72

Diffuse lung fibrosis ## Footnote Corticosteroids may be of value in some patients, but withdrawal of the amiodarone, if possible, is advised. In this case, other therapies such as an implantable defibrillator may be considered. Other drugs related to lung fibrosis include nitrofurantoin, hexamethonium and a number of cytotoxic agents.

Answer 73

RTA 1 ## Footnote Type 1 (distal RTA) occurs when a-intercalated cells in the distal and collecting tubules fail to secrete H+ and absorb K+: * distal (type 1) is common * can be associated with diabetes insipidus and salt-wasting states * metabolic acidosis (severe) and hypokalaemia * severe acidosis predesposes to urinary tract calculi * glomerular filtration rate (GFR) is often unaffected.

Answer 74

RTA 2 ## Footnote Type 2 (proximal RTA) occurs when proximal tubule cells fail to reabsorb bicarbonate: * it is relatively uncommon * potassium may be normal or low * metabolic acidosis (less severe) * associated with osteomalacia and rickets * GHR is often unaffected.

Answer 75

RTA 4 ## Footnote Type 4 - the kidney is either resistant to aldosterone, or plasma aldosterone levels are low: * associated with hyperkalaemia * commonly due to mineralocorticoid deficiency * chronic kidney disease (CKD) is usually present.

Answer 76

Chronic hyperuricaemia in gout where allopurinol cannot be tolerated ## Footnote In patients with severe or tophaceous gout, febuxostat may be preferred if more potent urate lowering is needed.

Answer 77

To assess for risk of rupture and the possible need for drainage ## Footnote Medical treatment involves oral metronidazole or tinidazole; surgical intervention is rarely required

Answer 78

Insulin stress test ## Footnote It stimulates the Hypothalamic-Pituitary Axis which induces hypoglycaemia, a potential stressor that stimulates: * CRH → ACTh → cortisol * GHRH → GH release

Answer 79

Seizure disorders Ischemic heart disease Elderly or frail patients Due to risk of symptomatic hypoglycaemia ## Footnote In these cases, alternative tests are considered (e.g., glucagon stimulation test, metyrapone test, macimorelin test for GH).

Answer 80

HAV = 2 - 6 weeks HBV = 6 weeks - 6 months

Answer 81

The simplified calculation (which omits potassium) to find the anion gap is that the gap is equal to [Na+] - ([CL] + [HCO3 ]) (all units mmol/l). ## Footnote The normal range is 8-16 mEq/l. Adjust for hypoalbuminaemia: ↓ AG by ~2.5 for every 10 g/L ↓ in albumin below normal (~40 g/L)

Answer 82

Large-airway obstruction (medical emergency) ## Footnote Flow-volume loops show typical flattening caused by large-airways obstruction. Stridor complicating cancer requires urgent treatment and this can include steroids, radiotherapy, chemotherapy or endobronchial stenting.

Answer 83

Hailey-Hailey disease (familial benign chronic pemphigus), like Darier's disease, is an **autosomal dominant disorder** and typically presents with **flaccid vesicles and blisters **and upon rupture forming painful erosions rather than warty papules or plaques. It predominantly affects intertriginous areas such as the neck folds rather than seborrhoeic regions like chest and back.

Answer 84

Plant-derived phenol that leads to improved energy metabolism ## Footnote Resveratrol activates the NAD⁺-dependent enzyme SIRT1 and the energy sensor AMPK, which together enhance the activity of PGC-1α, a key regulator of mitochondrial biogenesis. This leads to increased mitochondrial number and function, improved energy metabolism, and reduced oxidative stress.

Answer 85

IPF is a restrictive lung disease, which means: * FEV₁ (Forced Expiratory Volume in 1 second) is reduced * FVC (Forced Vital Capacity) is reduced * FEV₁/FVC ratio is normal or increased (often > 80%) ## Footnote Other typical lung function findings in IPF: ↓ Total Lung Capacity (TLC) ↓ Residual Volume (RV) ↓ Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

Answer 86

Antifibrotic drugs, such as pirfenidone and nintedanib, are thought to slow the rate of scarring. ## Footnote Oral N-acetyl-L-cysteine (NAC) can be used, but the benefits are uncertain. If already using prednisolone or azathioprine, discuss the potential risks and benefits of discontinuing, continuing or altering therapy.

Answer 87

Decreased lysosomal hydrolysis

Answer 88

* Fatal genetic lipid-storage disorder - results in build-up of ganglioside Gm2 (harmful) * Caused by mutation leading to deficiency of hexosaminidase A (Hex-A) enzyme

Answer 89

Rare, inherited kidney disorder caused by mutations (CLCN5/OCRL gene) that impair the function of kidney tubules, particularly proximal tubules.

Answer 90

Ocular ischaemic syndrome (OIS) on the side affected worse ## Footnote Chronic hypoperfusion due to carotid occlusion. It manifests as visual loss with or without pain, with signs including raised intraocular pressure, rubeosis iridis, anterior chamber cells, cataract, retinal haemorrhages, neovascularisation of the disc and retina, cotton-wool spots and micro-aneurysms. Typically, veins are dilated but non-tortuous, unlike in central retinal vein occlusion. Fluorescein angiography and carotid Doppler ultrasound are the investigations of choice, the latter typically showing >90% obstruction of the carotid artery. Cardiovascular risk factors should be identified and optimised.

Answer 91

Chemo + radiotherapy (especially if stage I or II) Targets bpth localised tumours (radiotherapy) + potential systemic spread (chemotherapy). ## Footnote ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regimens are commonly used,

Answer 92

Hypokalaemic periodic paralysis (HypoPP)

Answer 93

Increased prevalence of HLA B1502 genotype which is associated with increased risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Answer 94

Fluid loss can lead to increased viscosity. Increased viscosity, coupled with inflammation associated with SJS/TEN, drives a significant risk of venous thromboembolism, for which prophylactic anticoagulation should be considered.

Answer 95

Immunophenotyping by Flow Cytometry ## Footnote Allows precise classification of the blasts: * Distinguishes ALL from AML * Determines B-cell vs T-cell lineage in ALL It detects surface markers (e.g., CD10, CD19, CD3, TdT) on the blast cells.

Answer 96

Reduction of IGF-1 levels. ## Footnote Most clinical manifestations of acromegaly — such as enlarged hands, feet, facial features, and organomegaly — are driven by elevated IGF-1, which is produced in response to GH. Therefore, therapy aims to normalize IGF-1 rather than just GH alone.

Answer 97

Pegvisomant acts at peripheral GH receptors, not the pituitary. ## Footnote Somatostatin analogues suppress GH secretion at the pituitary gland. In contrast, pegvisomant binds GH receptors in the liver and other tissues, directly blocking the downstream signalling that leads to IGF-1 production.

Answer 98

Converts RNA into DNA ## Footnote Reverse transcriptase is a DNA polymerase enzyme that transcribes single-stranded RNA into complementary double-stranded DNA, enabling the integration of viral genetic material into the host genome. Reverse transcriptase enables the synthesis of complementary DNA (cDNA) from mRNA, allowing researchers to study gene expression and clone genes without introns.

Answer 99

DNA polymerase ## Footnote Although it acts on RNA templates, reverse transcriptase is classified as a DNA polymerase because it synthesizes DNA strands complementary to the RNA.

Answer 100

Unwinding the DNA double helix ## Footnote Helicases separate the two DNA strands to allow DNA polymerases and other enzymes access to single-stranded DNA during replication and repair.

Answer 101

Xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy ## Footnote Mutations in helicase or helicase-related proteins impair DNA repair mechanisms, leading to disorders characterised by defective nucleotide excision repair and increased UV sensitivity.

Answer 102

X-ray crystallography ## Footnote X-ray crystallography allows for detailed atomic-level visualization of protein structures but generally captures static conformations. It does not provide information on protein conformational changes over time. NMR and DPI provide insights into protein dynamics and conformational flexibility under near-physiological conditions.

Answer 103

Nuclear Magnetic Resonance (NMR) and Dual Polarisation Interferometry (DPI) ## Footnote NMR and DPI provide insights into protein dynamics and conformational flexibility under near-physiological conditions. Knowing the structure reveals why a receptor might be locked "on" or why certain substances fail to bind or activate targets, guiding drug design.

Answer 104

Excision of introns and joining of exons to produce mature mRNA. ## Footnote DNA splicing removes non-coding introns from pre-mRNA and joins coding exons together, enabling translation into functional peptides. By manipulating splicing, bacteria or yeast can be engineered to produce proteins like insulin or growth hormone for therapeutic use. Gene therapy can modify splicing mechanisms to correct genetic disorders by regulating protein production.

Answer 105

Western blotting. ## Footnote Western blotting separates proteins by size using gel electrophoresis, then detects specific proteins with antibodies, making it ideal for identifying proteins in complex mixtures.

Answer 106

It separates proteins by size and uses antibodies to detect the target protein on a membrane. ## Footnote Proteins are first separated by SDS-PAGE, transferred to a membrane, and probed with specific antibodies. Binding of antibodies reveals the presence and size of the protein.

Answer 107

Monocytes (Rarely, also: Smooth muscle cells and vascular dendritic cells) ## Footnote Foam cells are primarily derived from monocyte-macrophage lineage, as indicated by CD68 positivity. These monocytes migrate into the intima and uptake oxidised LDL, transforming into lipid-laden foam cells. Some foam cells express markers like actin, vimentin, and desmin (smooth muscle origin), while others express S-100 (a marker for vascular dendritic cells), suggesting multiple lineages in foam cell formation.

Answer 108

S-100 ## Footnote S-100 is a protein expressed by vascular dendritic cells and can be used to identify foam cells originating from this lineage.

Answer 109

Gelatinase (specifically B) ## Footnote The matrix metalloproteinases have a common structure. The three common domains are the propeptide, the catalytic domain, and the haemopexin-like C-terminal domain, which is linked to the catalytic domain by a flexible hinge region. MMP9 is a gelatinase, and it has functions in neutrophil action, angiogenesis and wound repair.

Answer 110

Proofreading ## Footnote The 3' to 5' exonuclease activity of DNA polymerase allows it to remove incorrectly paired nucleotides during DNA replication. This proofreading function helps maintain high fidelity of DNA synthesis by excising misincorporated bases and allowing correct nucleotides to be inserted. If the proofreading activity of DNA polymerase is defective, replication errors are not corrected, leading to an accumulation of mutations. This contributes to genomic instability, a key factor in the development of certain cancers, including hereditary non-polyposis colorectal cancer (HNPCC).

Answer 111

Defects in mismatch repair (MMR) genes ## Footnote Lynch syndrome (HNPCC) is caused by inherited mutations in DNA mismatch repair genes, such as MLH1, MSH2, MSH6, and PMS2. These genes correct errors missed by DNA polymerase proofreading. Defects result in microsatellite instability and a predisposition to colorectal and other cancers.

Answer 112

Proofreading occurs during replication; mismatch repair occurs after ## Footnote Proofreading is an intrinsic activity of DNA polymerase that occurs during DNA replication (3'→5' exonuclease). Mismatch repair (MMR) is a post-replication process that identifies and corrects errors missed during proofreading.

Answer 113

Lysosomes (using acid hydrolases) ## Footnote Lysosomes are membrane-bound organelles containing hydrolytic enzymes that degrade oligopeptides, nucleic acids, carbohydrates, and lipids. They function as the cell’s waste disposal system.

Answer 114

Inherited disorder due to enzyme deficiency in lysosomes ## Footnote Lysosomal storage diseases are a group of genetic disorders caused by deficiencies in specific lysosomal enzymes. This leads to accumulation of undigested macromolecules, resulting in cellular dysfunction and clinical symptoms.

Answer 115

Mast cells ## Footnote Mast cells are activated during the EAR due to IgE-mediated degranulation, releasing histamine and other mediators that cause bronchoconstriction and inflammation. They release histamine, leukotrienes, and prostaglandins. The EAR is rapid, peaking at around 15–30 minutes after allergen exposure, and usually resolves within 1–3 hours unless followed by a late-phase response.

Answer 116

They produce IgE after initial allergen exposure. ## Footnote B cells are responsible for the adaptive immune response and class-switching to IgE production under the influence of IL-4 and IL-13 (from Th2 cells). NOTE: main mechanism is mast cell degranulation.

Answer 117

Infiltration of inflammatory cells, especially eosinophils, into the airway. ## Footnote The LAR involves recruitment of eosinophils, T cells, and other inflammatory cells, leading to prolonged airway inflammation and hyperresponsiveness hours after allergen exposure. The LAR develops several hours after the EAR and can last for up to 24 hours or longer, causing sustained airway inflammation. The persistent inflammation during LAR can cause airway remodeling and chronic airflow limitation if untreated.

Answer 118

IL-4, IL-5, and IL-13. ## Footnote These Th2 cytokines promote eosinophil recruitment (IL-5), IgE production (IL-4), and mucus hypersecretion (IL-13), all contributing to ongoing airway inflammation.

Answer 119

Eosinophils and Th2 lymphocytes. ## Footnote These cells produce inflammatory mediators causing tissue damage and amplifying the inflammatory response.

Answer 120

p53 ## Footnote The p53 protein regulates programmed cell death (apoptosis) by inducing genes that control cell cycle arrest and apoptosis. HPV produces proteins (like E6) that inactivate p53, preventing apoptosis of damaged cells, leading to cancer development.

Answer 121

Induces expression of genes involved in programmed cell death and cell cycle arrest. ## Footnote p53 acts as a tumor suppressor by halting the proliferation of cells with DNA damage and triggering apoptosis if the damage is irreparable. Loss of p53 function leads to accumulation of genetic mutations and unchecked cell growth, promoting oncogenesis.

Answer 122

What is p51 and what is its clinical relevance? ## Footnote p51 is not involved in HPV-related carcinogenesis but is studied as a marker in colon cancer to predict likelihood of recurrence after treatment.

Answer 123

p52, also known as NF-kappa B2, is a transcription factor overexpressed in prostate cancer and may facilitate disease progression. ## Footnote p52 is part of the NF-kB family involved in immune responses and inflammation; abnormal activation can promote tumor growth and survival in some cancers.

Answer 124

p54 is a helicase protein that unwinds DNA and RNA and may be upregulated in certain cancers. ## Footnote Helicases like p54 are enzymes essential for DNA replication and repair. Dysregulation can contribute to genomic instability in tumors.

Answer 125

p55 is a membrane scaffold protein involved in cellular structure, not directly related to cancer pathogenesis. ## Footnote Scaffold proteins like p55 help organize cell membrane domains and signaling complexes but are not implicated in tumor suppression or promotion.

Answer 126

Cellular senescence is a state where cells stop dividing permanently, despite remaining metabolically active. This acts as a tumor suppressive mechanism to prevent the propagation of damaged or aged cells. ## Footnote Senescence can be triggered by telomere shortening during repeated cell divisions, causing a DNA damage response, and by other types of DNA damage or environmental stressors.

Answer 127

Around 50 cell divisions (the Hayflick limit). ## Footnote Leonard Hayflick discovered that normal cells have a limited number of divisions, after which they enter senescence, a natural barrier against uncontrolled proliferation and cancer.

Answer 128

To prevent autoimmune attack by immune cells. ## Footnote Encapsulation creates a physical barrier, usually with alginate, that prevents immune cells—primarily T lymphocytes—from accessing and destroying the transplanted islet cells, thereby protecting them from autoimmune destruction in type 1 diabetes. The physical barrier created by encapsulation limits blood vessel growth around the transplant, which can affect nutrient and oxygen supply but is a trade-off for protection from immune attack.

Answer 129

Alginate ## Footnote Alginate is a biocompatible polymer used to encapsulate islet cells. It forms a semi-permeable barrier allowing nutrients and insulin to pass while blocking immune cells. Although encapsulation limits some aspects of vascularisation, the ability of the islet cells to sense glucose and release insulin remains largely intact, preserving therapeutic effectiveness.

Answer 130

The hydrogen-transfer chain in mitochondria ## Footnote Riboflavin is crucial for redox reactions in the mitochondrial electron transport chain. It forms key cofactors like FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide), both essential for ATP production.

Answer 131

To prevent autoimmune attack by immune cells. ## Footnote Encapsulation creates a physical barrier, usually with alginate, that prevents immune cells—primarily T lymphocytes—from accessing and destroying the transplanted islet cells, thereby protecting them from autoimmune destruction in type 1 diabetes. The physical barrier created by encapsulation limits blood vessel growth around the transplant, which can affect nutrient and oxygen supply but is a trade-off for protection from immune attack.

Answer 132

Alginate ## Footnote Alginate is a biocompatible polymer used to encapsulate islet cells. It forms a semi-permeable barrier allowing nutrients and insulin to pass while blocking immune cells. Although encapsulation limits some aspects of vascularisation, the ability of the islet cells to sense glucose and release insulin remains largely intact, preserving therapeutic effectiveness.

Answer 133

The hydrogen-transfer chain in mitochondria ## Footnote Riboflavin is crucial for redox reactions in the mitochondrial electron transport chain. It forms key cofactors like FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide), both essential for ATP production.

Answer 134

No ## Footnote Riboflavin is water-soluble and not stored in significant amounts, making regular intake essential. Deficiency may develop quickly in malnourished or alcoholic individuals.

Answer 135

Stimulates GnRH secretion to promote satiety ## Footnote Leptin stimulates the hypothalamus to release gonadotrophin-releasing hormone (GnRH), which in turn triggers the anterior pituitary to release LH and FSH. This links nutritional status to reproductive function, ensuring that adequate energy stores are present before fertility is supported.

Answer 136

Stavudine, Didanosine, Indinavir ## Footnote These antiretroviral drugs, particularly older nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), are linked to lipodystrophy, characterized by central fat accumulation and peripheral fat loss. In lipodystrophy, leptin levels are often low, contributing to metabolic dysfunction and possibly reproductive suppression. Supplementation can improve insulin sensitivity, reduce fat mass, and restore hypothalamic-pituitary axis function.

Answer 137

L-arginine ## Footnote Nitric oxide (NO) is synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). This process is essential in various physiological functions including vasodilation and neurotransmission.

Answer 138

Nitric oxide synthase (NOS) ## Footnote There are three main types of NOS: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). In the corpus cavernosum, eNOS is primarily responsible for NO production during sexual stimulation.

Answer 139

Asteroid bodies ## Footnote Asteroid bodies are star-shaped inclusions occasionally found in multinucleated giant cells in sarcoid granulomas. Though not pathognomonic, their presence supports the diagnosis. Sarcoid granulomas lack central necrosis (non-caseating) and are composed of tightly clustered epithelioid cells, multinucleated giant cells, and T lymphocytes.

Answer 140

Large veins ## Footnote Nitrates primarily dilate large capacitance veins, reducing venous return (preload) to the heart. This decreases ventricular wall tension and myocardial oxygen demand, making them effective for angina and acute heart failure. While they also cause some arterial dilation, their venodilatory effect is more pronounced at therapeutic doses.

Answer 141

They reduce preload and pulmonary congestion ## Footnote In left ventricular failure, elevated preload leads to pulmonary congestion. Nitrates dilate veins, reducing preload and improving hemodynamics. This alleviates dyspnoea and pulmonary oedema, especially when associated with hypertension or ischaemia.

Answer 142

Somatic cell nuclear transfer (SCNT) ## Footnote In SCNT, the nucleus from a donor somatic cell is inserted into an enucleated oocyte (an egg cell from which the nucleus has been removed). The resulting cell has the genetic material of the donor and can potentially develop into an embryo. This method was famously used to clone Dolly the sheep. Goal of SCNT in the context of diabetes: To generate insulin-producing cells or organs for transplantation

Answer 143

HPS is a rare autosomal recessive disorder characterized by oculocutaneous albinism, bleeding tendency, and lysosomal storage defect due to abnormal dense granules in platelets. ## Footnote Results from a mutation in the AP3 gene

Answer 144

Phosphorylation by viral thymidine kinase to aciclovir monophosphate. ## Footnote Acyclovir is first phosphorylated by the viral enzyme thymidine kinase, which is present only in virus-infected cells. This step is crucial for selective activation of the drug in infected cells.

Answer 145

Host cell kinases convert aciclovir monophosphate to the active triphosphate form. ## Footnote After viral thymidine kinase phosphorylates aciclovir to monophosphate, cellular kinases add two more phosphate groups to form aciclovir triphosphate, which inhibits viral DNA polymerase.

Answer 146

Because phosphorylation to the monophosphate form is dependent on viral thymidine kinase, only infected cells activate the drug. ## Footnote Uninfected cells lack the viral kinase, so aciclovir remains inactive, reducing toxicity to normal host cells.

Answer 147

p53 promotes growth arrest at the G1/S checkpoint in response to DNA damage. ## Footnote p53 detects DNA damage and halts cell cycle progression at G1/S, allowing time for repair or triggering apoptosis if damage is irreparable, preventing propagation of mutations.

Answer 148

C282Y (+++) and H63D ## Footnote Symptoms: Excessive iron absorption, liver cirrhosis, diabetes, skin pigmentation, cardiomyopathy

Answer 149

Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness

Answer 150

Carrier frequency is about 1 in 350; prevalence approximately 1 in 770,000

Answer 151

Higher risk of developing Type 1 diabetes

Answer 152

Valine replaces glutamic acid at position 6 of the β-globin chain. ## Footnote Sickle cell anaemia results from a missense mutation in the HBB gene on chromosome 11. The mutation leads to substitution of valine for glutamic acid at position 6 of the β-globin chain, forming HbS (sickle haemoglobin) instead of normal HbA. This structural change causes haemoglobin to polymerize under low oxygen conditions, distorting red blood cells into a sickle shape.

Answer 153

Haemoglobin S (HbS) ## Footnote In sickle cell disease, red blood cells contain HbS, which has reduced solubility. Under deoxygenated conditions, HbS polymerizes, distorting red blood cells into sickled shapes that are less flexible and prone to vaso-occlusion and haemolysis.

Answer 154

CGG triplet repeat expansion in the FMR1 gene ## Footnote Fragile X syndrome is caused by a trinucleotide repeat expansion (CGG) in the FMR1 gene on the X chromosome. When the number of CGG repeats exceeds 200, the gene becomes methylated and silenced, reducing production of the FMRP protein, which is crucial for synaptic function and brain development.

Answer 155

Long face, prominent ears, hypermobile joints Also: Intellectual disability, social anxiety, learning difficulties ## Footnote Characteristic physical features include a long narrow face, large/prominent ears, macroorchidism (post-puberty), and joint hypermobility. These may become more pronounced with age. Individuals often have global developmental delay, moderate intellectual disability, difficulty with learning new tasks, and anxiety around social interactions. Features often overlap with autism spectrum disorder (ASD).

Answer 156

55–200 CGG repeats in the FMR1 gene ## Footnote (55–200 CGG repeats) doesn’t cause Fragile X syndrome itself but can expand in subsequent generations, especially when passed by a female. Premutation carriers may also develop fragile X-associated tremor/ataxia syndrome (FXTAS) or primary ovarian insufficiency.

Answer 157

Deletion on chromosome 7q11.23 ## Footnote Williams syndrome is caused by a microdeletion of about 26–28 genes on chromosome 7q11.23, including the ELN gene (elastin). This deletion is usually sporadic and confirmed via FISH or microarray testing. Children with Williams syndrome often have a distinctive facial appearance described as "elfin-like", including broad forehead, short nose with upturned tip, full cheeks and lips, and wide mouth with full lips.

Answer 158

Supravalvular aortic stenosis ## Footnote Due to ELN gene deletion, patients are prone to connective tissue defects, especially supravalvular aortic stenosis, but may also have renal artery stenosis or other vascular abnormalities.

Answer 159

Myotonic Dystrophy Type 1 (DM1) ## Footnote DM1 is a multisystem disorder caused by a CTG trinucleotide repeat expansion in the DMPK gene. Features include cardiac conduction defects, progressive muscle weakness, ptosis, frontal balding, cataracts, diabetes, and myotonia (delayed relaxation of hand grip).

Answer 160

Conduction defects (e.g., PR prolongation, bundle branch block) ## Footnote Conduction system disease is a hallmark of DM1. Patients are at increased risk of bradyarrhythmias, complete heart block, and sudden cardiac death, independent of skeletal muscle weakness severity.

Answer 161

Delayed muscle relaxation after contraction ## Footnote In DM1, myotonia is often seen as delayed release of grip (as in shaking hands). It's due to membrane hyperexcitability in muscle fibers and can be confirmed with EMG.

Answer 162

Right coronary artery (RCA) ## Footnote The RCA supplies the AV node via the posterior interventricular artery (in ~85% of people). Infarction of the RCA can result in ischemia to the AV node, causing bradycardia and complete heart block, especially in inferior myocardial infarctions.

Answer 163

Bradycardia and hypotension ## Footnote Complete heart block (3rd-degree AV block) often presents with a slow heart rate (e.g., 40 bpm), hypotension, and sometimes syncope. It can occur acutely following an RCA infarct affecting the AV node.

Answer 164

Peri-articular erosions ## Footnote Periarticular erosions on X-ray are characteristic of RA and reflect aggressive synovial inflammation leading to joint destruction. These changes usually occur in small joints (e.g., MCP, PIP) and are key in distinguishing RA from other arthritides like osteoarthritis.

Answer 165

Anti-Jo-1 ## Footnote Anti-Jo-1 is one of the antisynthetase antibodies and is associated with dermatomyositis and polymyositis, particularly when interstitial lung disease (ILD) is also present. It's a marker for antisynthetase syndrome, a subset of inflammatory myopathies.

Answer 166

Methotrexate ## Footnote Methotrexate is the cornerstone DMARD for RA. It’s effective but requires close monitoring due to risk of bone marrow suppression, hepatotoxicity, and pneumonitis. A short course of oral prednisolone is often used while waiting for DMARDs to take effect, which can take several weeks.

Answer 167

Sulfasalazine ## Footnote Sulfasalazine is generally safe in pregnancy and often used in women planning conception or during gestation. It may cause reversible oligospermia in men.

Answer 168

Benzydamine mouthwash ## Footnote Benzydamine hydrochloride is a topical NSAID that provides local anti-inflammatory and analgesic effects. It is available as a mouthwash or spray, and is especially useful for painful mucositis or oral discomfort in palliative settings. Chlorhexidine is an antiseptic used to treat or prevent oral infections, such as oral thrush or bacterial overgrowth. While helpful for hygiene, it is not primarily analgesic.

Answer 169

Sandfly bite ## Footnote The disease is transmitted by the bite of infected female phlebotomine sandflies, typically in tropical and subtropical regions including parts of Central and South America.

Answer 170

Nasal/mucosal involvement ## Footnote Unlike cutaneous leishmaniasis, the mucocutaneous form affects mucosal tissues (e.g., nasal septum, pharynx), and may lead to destructive lesions. The systemic symptoms such as fever, weight loss, and high CRP reflect immune response or secondary infection.

Answer 171

Verrucous or nodular skin lesions ## Footnote Cutaneous blastomycosis often presents with ulcerated, verrucous, or nodular lesions that may resemble squamous cell carcinoma. These usually occur due to hematogenous spread from a primary pulmonary infection.

Answer 172

Mucosal destruction ## Footnote Leishmania braziliensis causes destructive mucosal ulcers (e.g., nasal septum), often weeks to months after a skin lesion. In contrast, blastomycosis usually involves verrucous skin lesions and rarely affects mucosa unless disseminated.

Answer 173

Japanese encephalitis ## Footnote Japanese encephalitis virus (JEV) is transmitted by Culex mosquitoes, particularly in rice paddy fields. It is the leading cause of viral encephalitis in Southeast Asia, China, and India. Most infections are asymptomatic, but severe cases cause encephalitis with neurological symptoms.

Answer 174

By Culex mosquitoes ## Footnote The virus is transmitted through bites from Culex mosquitoes, which breed in stagnant water like rice paddies. Humans are incidental hosts.

Answer 175

Parkinsonism features ## Footnote Parkinsonism—including resting tremor, rigidity, and bradykinesia—indicates basal ganglia damage. In Japanese encephalitis, these symptoms are characteristic of more severe or advanced disease.

Answer 176

Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) ## Footnote Respiratory involvement is the leading cause of death, especially pulmonary arterial hypertension causing right heart failure, and interstitial lung disease causing respiratory failure. PAH leads to increased pulmonary vascular resistance, causing right ventricular hypertrophy and failure, which is a common terminal event in systemic sclerosis.

Answer 177

Risk of scleroderma renal crisis ## Footnote Systemic sclerosis can cause scleroderma renal crisis, characterized by sudden severe hypertension and acute kidney injury, which requires urgent treatment but is less common than pulmonary causes of death.

Answer 178

Cytogenetics Good prognosis: t(8;21), inv(16), t(15;17) Poor prognosis: Complex karyotype, monosomy 5 or 7, 11q23 abnormalities ## Footnote Cytogenetic analysis identifies chromosomal abnormalities that strongly influence prognosis and treatment response in AML. It helps classify patients into favorable, intermediate, or poor risk groups, guiding therapeutic decisions.

Answer 179

Myopia ## Footnote Myopia (nearsightedness) is a recognized risk factor for POAG, possibly due to changes in optic nerve head and eye shape. Hypermetropia (farsightedness) is associated with acute angle-closure glaucoma due to anatomical predisposition to narrow angles.

Answer 180

Progressive massive fibrosis (PMF) ## Footnote PMF is a severe form of pneumoconiosis, often affecting coal miners. It is characterized by large fibrotic masses in the upper lobes, mixed lung function defects, and history of dust exposure. Chest imaging in PMF typically shows bilateral apical fibrosis with masses up to 10 cm, along with signs of emphysema and lung destruction, especially in heavy dust exposure settings.

Answer 181

Mixed obstructive and restrictive pattern ## Footnote PMF affects both the airways and lung parenchyma, leading to airflow obstruction (like COPD) and restriction from fibrosis. There is also reduced gas transfer (DLCO).

Answer 182

Around 30% ## Footnote According to ILO classification, category 3 (dense small opacities) has a high risk of progression to PMF. Category 2 has a 7% progression rate, while category 3 is significantly more severe.

Answer 183

Familial primary pulmonary hypertension ## Footnote PPH typically presents in young to middle-aged women with exertional dyspnoea and signs of right heart strain. A positive family history supports a familial (heritable) form, which follows an autosomal dominant pattern with incomplete penetrance.

Answer 184

Elevated JVP, left parasternal heave, pansystolic murmur ## Footnote JVP elevation indicates right atrial pressure rise. Parasternal heave shows right ventricular hypertrophy. Pansystolic murmur suggests tricuspid regurgitation due to RV dilation. Right ventricular S4 - indicates a stiff right ventricle from hypertrophy, common in pulmonary hypertension. It’s best heard at the lower left sternal edge.

Answer 185

Left-sided heart disease (e.g. mitral valve disease, LV failure) ## Footnote PVH is most commonly secondary to conditions that raise left atrial pressure, such as mitral stenosis, mitral regurgitation, or left ventricular dysfunction, leading to elevated pulmonary capillary wedge pressure (>14 mmHg).

Answer 186

Immune reconstitution inflammatory syndrome (IRIS) with reactivation TB ## Footnote IRIS occurs when the recovering immune system mounts an inflammatory response to latent infections like TB after HAART is started. The timeline, chest X-ray, and history support reactivation of latent TB. IRIS usually occurs within 2–8 weeks of initiating antiretroviral therapy, especially in patients with low CD4 counts, as immune function rapidly improves.

Answer 187

Tuberculosis, cryptococcus, CMV, MAC ## Footnote TB is the most common. These pathogens may have been latent or subclinical before HAART and become symptomatic due to a newly reactive immune system.

Answer 188

Widespread nodular infiltrates and pleural effusions ## Footnote The chest X-ray in this case shows bilateral effusions and nodular consolidation, which is consistent with miliary or disseminated TB.

Answer 189

Consider isoniazid prophylaxis in high-risk patients ## Footnote Patients from high TB prevalence regions (like Afghanistan) with a past history of TB or positive screening may benefit from prophylactic treatment before or alongside HAART to prevent IRIS-related reactivation.

Answer 190

Intravenous (or high-dose oral) co-trimoxazole Can also give steroids if PaO₂ <70 mmHg or SpO₂ <92% on room air IV pentamidine is used if co-trimoxazole cannot be tolerated or if the patient is critically ill, but it carries more toxicity. ## Footnote Co-trimoxazole (trimethoprim-sulfamethoxazole) is the standard treatment. IV administration is preferred in moderate to severe cases, especially when the patient is unwell or hypoxic. PJP classically presents with subacute dry cough, dyspnoea, and hypoxia. Chest X-ray often shows bilateral ground-glass infiltrates, especially in immunocompromised patients with CD4 <200 cells/mm³.

Answer 191

Elevated lactate dehydrogenase (LDH) ## Footnote LDH is non-specific, but is elevated in ~90% of PJP cases. A high LDH in an HIV patient with respiratory symptoms should raise suspicion. PJP is an AIDS-defining illness, and prophylaxis with co-trimoxazole is recommended when CD4 falls below this level.

Answer 192

FEV₁ (forced expiratory volume in 1 second) PEFR (peak expiratory flow rate) ## Footnote Both are used to assess airway obstruction, but FEV₁ provides a traced volume-time curve, while PEFR is more suitable for self-monitoring. FEV₁ provides a visible, reproducible volume-time tracing. This allows clinicians to verify the quality of effort and assess whether the test was performed correctly. PEFR lacks this precision. PEFR meters are portable and inexpensive, enabling patients to detect early declines in lung function and adjust treatment accordingly.

Answer 193

Used for bronchial thermoplasty in severe asthma ## Footnote In selected patients with severe, refractory asthma, bronchoscopy is used to deliver bronchial thermoplasty, a procedure that reduces airway smooth muscle and aims to reduce bronchial hyperresponsiveness.

Answer 194

Staphylococcus aureus ## Footnote In adolescents and young adults with CF, Staphylococcus aureus remains a common respiratory pathogen, especially in the late teens, although Pseudomonas aeruginosa becomes more dominant with age. Chronic colonization with P. aeruginosa increases with age and is associated with more severe lung disease and faster decline in lung function in CF. Empirical treatment should include agents active against gram-positive cocci (e.g. flucloxacillin) and gram-negative rods (e.g. ceftazidime or tobramycin), tailored to culture results when available.

Answer 195

Streptococcus pneumoniae ## Footnote Classic cause of CAP, often associated with HSV-1 reactivation and bilateral consolidation; requires urgent hospital assessment.

Answer 196

Positive cold agglutinins NOTE: WCC is often normal ## Footnote Around 50% of patients with Mycoplasma have cold agglutinins, which are autoantibodies that agglutinate red cells at cold temperatures. It's not specific but is suggestive. In contrast to typical bacterial pneumonias, WCC is often normal or only mildly raised in Mycoplasma infections.

Answer 197

Macrolides (e.g. clarithromycin or azithromycin) ## Footnote Since Mycoplasma lacks a cell wall, β-lactams are ineffective. Use a macrolide, or consider doxycycline or fluoroquinolones as alternatives.

Answer 198

Serum immunoglobulins ## Footnote Measurement of IgG, IgA, and IgM helps detect immune deficiencies, which are a common cause of recurrent respiratory infections and bronchiectasis. Elevated IgE can also suggest allergic bronchopulmonary aspergillosis (ABPA). Workup should include testing for CF (in young patients), immune dysfunction, ABPA, and ciliary disorders (e.g., primary ciliary dyskinesia).

Answer 199

Elevated IgE, asthma history, and central bronchiectasis ## Footnote ABPA is often seen in asthmatics, and involves hypersensitivity to Aspergillus. It can cause central bronchiectasis, eosinophilia, and elevated IgE.

Answer 200

* previous diagnosis of asthma or atopy * a higher blood eosinophil count * substantial variation in FEV1 over time (at least 400 ml) * substantial diurnal variation in peak expiratory flow (at least 20%)

Answer 201

50× greater risk ## Footnote Asbestos exposure increases risk ~5×, smoking ~10–11×. Together, the risk is multiplicative, not just additive, giving a combined risk of around 50×.

Answer 202

Bronchial carcinoma (especially squamous and adenocarcinoma) ## Footnote While mesothelioma is pathognomonic for asbestos, the major cause of death from asbestos exposure is actually bronchial carcinoma, especially in smokers.

Answer 203

Bronchiectasis ## Footnote While some airway dilatation can be reversible during acute infection, true bronchiectasis is a chronic, irreversible dilatation of the bronchi due to damage from repeated or severe infections. HRCT is the gold standard for showing airway dilatation and bronchial wall thickening, diagnostic of bronchiectasis.

Answer 204

Marked eosinophilia (>1.0 × 10⁹/L) ## Footnote Peripheral blood eosinophilia is a hallmark of EGPA, often >10% of white cells, as seen here (eosinophils 1.3 × 10⁹/L). P-ANCA (perinuclear anti-neutrophil cytoplasmic antibody), often against myeloperoxidase (MPO) - occurs in approximately 40-60% of EGPA cases and helps support the diagnosis.

Answer 205

Mononeuritis multiplex ## Footnote This refers to damage of multiple individual peripheral nerves, causing asymmetric sensory and motor symptoms.

Answer 206

Tricuspid valve ## Footnote Carcinoid syndrome commonly causes fibrotic changes in right-sided heart valves, especially the tricuspid valve, leading to tricuspid regurgitation. This is due to serotonin and other vasoactive substances secreted into the venous circulation before being metabolized in the lungs.

Answer 207

Tryptophan ## Footnote Serotonin (5-HT) is synthesized from the amino acid tryptophan. In carcinoid tumors, increased tryptophan metabolism to serotonin can lead to tryptophan deficiency and sometimes niacin deficiency (pellagra).

Answer 208

Because the liver normally metabolizes serotonin ## Footnote In localized (non-metastatic) intestinal carcinoid tumors, serotonin is metabolized by the liver and doesn't reach systemic circulation. Carcinoid syndrome typically only occurs when there are liver metastases bypassing hepatic metabolism.

Answer 209

Activates adenylate cyclase ## Footnote Glucagon binds to its receptor on hepatocytes, activating adenylate cyclase, which increases cyclic AMP (cAMP). This triggers a cascade that activates protein kinase A, leading to glycogenolysis (breakdown of glycogen) and gluconeogenesis, rapidly increasing blood glucose levels. If hepatic glycogen is low (e.g., in malnutrition, liver disease, or prolonged fasting), glucagon may be less effective at correcting hypoglycaemia.

Answer 210

By low urinary calcium in Gitelman syndrome ## Footnote Both syndromes cause hypokalaemic metabolic alkalosis with normotension, but Gitelman syndrome has low urinary calcium, while Bartter syndrome typically shows normal or high urinary calcium. Bartter syndrome also presents earlier in life, often in infancy or childhood.

Answer 211

Metabolic alkalosis ## Footnote Loss of sodium and chloride leads to volume contraction, stimulating aldosterone release. Aldosterone promotes hydrogen and potassium loss in the kidney, leading to metabolic alkalosis and hypokalaemia. Gitelman syndrome leads to chronic potassium loss due to defective sodium-chloride transport in the distal tubule. This hypokalaemia can manifest as fatigue, muscle cramps, or episodes of fainting due to mild volume depletion.

Answer 212

Pituitary adenomas suppress cortisol >50% on high-dose dexamethasone; ectopic ACTH tumors do not suppress. ## Footnote The high-dose dexamethasone suppression test involves administering 2 mg dexamethasone every 6 hours for 48 hours. In Cushing’s disease (pituitary adenoma), cortisol production is partially suppressible by high-dose dexamethasone, leading to >50% decrease in serum cortisol or >90% decrease in urinary free cortisol. This is because the pituitary retains some feedback sensitivity. In contrast, ectopic ACTH-producing tumors secrete ACTH autonomously, so cortisol levels fail to suppress despite high-dose dexamethasone.

Answer 213

Suggests vitamin D deficiency with secondary hyperparathyroidism. ## Footnote Hypocalcaemia from vitamin D deficiency triggers increased parathyroid hormone secretion, which normalises calcium by resorbing bone but causes phosphate wasting. Elevated alkaline phosphatase reflects increased bone turnover due to PTH activity.

Answer 214

21-hydroxylase deficiency (90% of cases). Others: 11-hydroxylase deficiency (5%) and 17-hydroxylase/side-chain cleavage enzyme deficiency (very rare). ## Footnote 21-hydroxylase deficiency impairs conversion of 17-hydroxyprogesterone to 11-deoxycortisol, reducing cortisol and sometimes aldosterone production, and causing accumulation of androgen precursors. These rarer forms affect other steps in adrenal steroidogenesis, causing different hormonal imbalances and clinical features (e.g., hypertension in 11-hydroxylase deficiency).

Answer 215

Total thyroidectomy. ## Footnote In patients with severe thyroid eye disease (TED), especially smokers who are at higher risk of TED worsening, radioiodine therapy can exacerbate eye symptoms. Since the patient has relapsed twice after medical treatment and has active, severe TED, total thyroidectomy is preferred. Surgery avoids the risk of worsening eye disease associated with radioiodine and offers definitive control of hyperthyroidism. Additionally, management of TED often requires corticosteroids and supportive eye care.

Answer 216

It can worsen thyroid eye disease, especially in smokers. ## Footnote Radioiodine therapy often exacerbates or precipitates worsening of thyroid eye disease (TED), particularly in patients with active or severe TED and in smokers, who have a significantly higher risk. Smoking increases oxidative stress and immune activation in orbital tissues, worsening inflammation. Therefore, in such patients, alternative definitive treatments like total thyroidectomy are preferred, and if radioiodine is used, prophylactic corticosteroids are essential.

Answer 217

12–18 months of thionamide therapy, primarily carbimazole after the first trimester. ## Footnote Thionamides (carbimazole and propylthiouracil) are the mainstay of medical treatment for Graves’ disease. Propylthiouracil (PTU) is preferred during the first trimester of pregnancy due to lower risk of teratogenicity (e.g., aplasia cutis linked to carbimazole). However, due to PTU’s risk of hepatotoxicity, patients should be monitored closely. After the first trimester, treatment is usually switched to carbimazole because of better safety and efficacy profiles. Treatment generally continues for 12–18 months with the aim of inducing remission. Definitive treatment (radioiodine or surgery) is usually deferred until after pregnancy.

Answer 218

* Arterial pH < 7.3 OR * INR > 6.5 AND creatinine > 300 µmol/L AND grade 3 or 4 encephalopathy ## Footnote These criteria identify patients with a poor prognosis who may benefit from urgent liver transplant. Either profound acidosis (pH < 7.3) or a combination of coagulopathy, renal failure, and severe encephalopathy are used. Meeting either threshold qualifies for super-urgent transplant referral.

Answer 219

Rapid onset of liver dysfunction with coagulopathy and encephalopathy in a previously healthy liver ## Footnote ALF is characterised by: * Elevated transaminases (e.g., ALT > 1000 IU/L in paracetamol overdose) * Coagulopathy (INR > 1.5) * Hepatic encephalopathy * No history of chronic liver disease * Paracetamol overdose is a leading cause, especially in young adults.

Answer 220

Albendazole and surgical removal or PAIR (puncture–aspiration–injection–reaspiration) ## Footnote Albendazole is used to reduce cyst viability. Surgical resection or PAIR technique is often needed for large or symptomatic cysts. Care must be taken to avoid cyst rupture during intervention.

Answer 221

Anaphylaxis ## Footnote Rupture of a hydatid cyst, especially into the peritoneum or lungs, can release antigenic fluid causing a life-threatening anaphylactoid reaction in around 2% of cases.

Answer 222

Ampulla of Vater ## Footnote Obstruction at the ampulla of Vater blocks both the common bile duct and pancreatic duct, leading to elevated bilirubin (jaundice) and amylase (pancreatitis). This is often caused by gallstones impacted at the ampulla.

Answer 223

Immediate IV N-acetylcysteine (NAC) ## Footnote When the timing of ingestion is uncertain, and especially if INR is raised, N-acetylcysteine should be started immediately. NAC prevents hepatic damage by replenishing glutathione, detoxifying the toxic metabolite NAPQI. Delaying treatment can significantly increase the risk of acute liver failure.

Answer 224

Bone scintigraphy (bone scan). ## Footnote Bone scintigraphy is highly sensitive for detecting early bone metastases by identifying increased osteoblastic activity. It can detect lesions before they are visible on X-rays or CT scans.

Answer 225

Osteoblastic lesions ## Footnote Prostate cancer typically causes osteoblastic (sclerotic) rather than lytic bone lesions. These increase bone density and are often detected as areas of increased uptake on a bone scan.

Answer 226

ACE inhibitors ## Footnote ACE inhibitors slow the progression of diabetic nephropathy by reducing intraglomerular pressure and proteinuria. They are first-line in diabetic patients with microalbuminuria or proteinuria, even in the absence of hypertension. For diabetics with microalbuminuria or early nephropathy, guidelines recommend a tighter blood pressure target (<130/80 mmHg) to prevent progression to overt nephropathy and reduce cardiovascular risk. Microalbuminuria (30–300 mg/day of albumin in urine) indicates early kidney damage in diabetes. Its presence signals increased cardiovascular and renal risk, necessitating prompt intervention.

Answer 227

Sterile pyuria ## Footnote Sterile pyuria—white cells in urine without bacterial growth on culture—is a classic finding in genitourinary TB. It reflects inflammation due to mycobacterial infection rather than typical uropathogens. Urinary tract TB should be suspected in patients from endemic areas presenting with sterile pyuria (white cells but no bacterial growth), systemic symptoms (fever, weight loss, night sweats), and constitutional signs like cough.

Answer 228

CT urography ## Footnote CT urography is highly sensitive in detecting structural changes in renal TB, such as papillary necrosis, ureteral strictures, and calcification. It also helps assess extent of renal damage or obstruction.

Answer 229

Three early morning urine samples for AFB microscopy and culture. ## Footnote Diagnosis is supported by acid-fast bacilli seen on Ziehl-Neelsen stain and confirmed by mycobacterial culture, which may take 2–4 weeks. Early morning samples maximize yield due to overnight concentration.

Answer 230

Nicorandil ## Footnote Nicorandil, used for angina, can cause painful ulcers of the mouth, skin, and GI tract. These are often severe, resistant to standard treatments, and resolve only after the drug is stopped. Ulcers due to nicorandil are typically refractory to antibiotics or corticosteroids. Stopping the drug usually leads to healing, and alternative antianginal therapy should be considered.

Answer 231

CYP3A4 ## Footnote Simvastatin is extensively metabolized by cytochrome P450 3A4. Clarithromycin is a potent CYP3A4 inhibitor, increasing simvastatin levels and the risk of myopathy or rhabdomyolysis.

Answer 232

Retinaldehyde (retinal) ## Footnote Retinaldehyde, particularly 11-cis-retinal, binds to opsin proteins in photoreceptors to form rhodopsin. This is essential for light detection in rod cells, which are critical for night vision. Vitamin A deficiency impairs the regeneration of rhodopsin in rod cells, leading to reduced vision in dim light—an early and reversible symptom of deficiency.

Answer 233

It isomerises to all-trans-retinal. ## Footnote Light causes 11-cis-retinal to convert to all-trans-retinal, triggering a conformational change in rhodopsin and initiating the phototransduction cascade, resulting in a neural signal.

Answer 234

Sodium bicarbonate ## Footnote Sodium bicarbonate is the first-line antidote for TCA toxicity with cardiac involvement. It combats sodium channel blockade by increasing serum sodium and alkalinizing the blood, reducing drug binding to cardiac sodium channels. Alkalinization of blood reduces the affinity of TCAs for cardiac sodium channels, stabilizing cardiac membranes and improving conduction.

Answer 235

Broad QRS complexes ## Footnote TCAs block fast sodium channels in the myocardium, leading to QRS widening (>100 ms) and risk of life-threatening arrhythmias like ventricular tachycardia or fibrillation.

Answer 236

Rapidly progressive glomerulonephritis (RPGN). ## Footnote Syphilis can lead to immune complex-mediated glomerulonephritis, often presenting with haematuria, proteinuria, and acute kidney injury, as seen with the raised creatinine in this case.

Answer 237

An acute febrile reaction following treatment of spirochaetal infections; managed with prednisolone if severe. ## Footnote Occurs within hours of initiating treatment for syphilis due to sudden spirochaete lysis. It is self-limiting but may require corticosteroids if severe, especially with CNS involvement.

Answer 238

Prochlorperazine Managed with anticholinergic drugs such as benzatropine or procyclidine. ## Footnote Prochlorperazine, a dopamine antagonist, can cause extrapyramidal side effects including acute dystonia (e.g., torticollis), especially in young women. These medications restore the dopamine-acetylcholine balance in the basal ganglia, relieving dystonic symptoms.

Answer 239

Minocycline ## Footnote Minocycline, a tetracycline antibiotic, can cause reversible blue-grey discoloration of the skin, especially after months of therapy. Minocycline is frequently used in dermatology for inflammatory skin conditions such as rosacea and acne vulgaris.

Answer 240

Hydralazine, procainamide, and isoniazid. ## Footnote These drugs are well-known for their potential to induce lupus-like syndromes. The risk is often related to dose and duration of exposure. The risk of hydralazine-induced lupus is dose-dependent. Higher cumulative doses and longer duration of therapy increase the likelihood of developing drug-induced lupus.

Answer 241

Above 5 mmol/L Or above 4 mmol/L when there is renal impairment (creatinine > 150 µmol/L). Or above 2.5 mmol/L if the patient has significant toxicity (seizures, decreased consciousness), renal insufficiency, or conditions limiting lithium excretion (e.g., heart failure). ## Footnote Haemodialysis is recommended if serum lithium is greater than 5 mmol/L regardless of symptoms, due to the risk of severe toxicity.

Answer 242

Cyclophosphamide and prednisolone. ## Footnote The combination of high-dose corticosteroids and cyclophosphamide is the gold-standard induction therapy for generalised ANCA-associated vasculitis with organ-threatening disease.

Answer 243

PR3-ANCA (GPA) and MPO-ANCA (MPA). ## Footnote PR3 (proteinase-3) ANCA is more common in GPA; MPO (myeloperoxidase) ANCA is associated with MPA, though overlap can occur.

Answer 244

Schistosoma mansoni ## Footnote Schistosoma mansoni, endemic in Brazil and other parts of South America, can cause immune complex-mediated glomerulonephritis, leading to proteinuria or nephrotic syndrome, particularly in chronic infection with hepatosplenic involvement.

Answer 245

Hepatosplenic disease (portal hypertension, splenomegaly). ## Footnote Chronic infection can lead to periportal fibrosis and portal hypertension, often with splenomegaly and haematological abnormalities. Initial exposure often causes a skin reaction (swimmer’s itch) as cercariae penetrate the skin, followed by a febrile systemic illness during the acute stage.

Answer 246

Haemorrhagic fever and pulmonary-renal syndrome. ## Footnote Hantavirus causes a severe illness characterized by capillary leak, leading to pulmonary oedema, acute kidney injury, hypotension, and in some cases, haemorrhagic complications. It is not typically associated with isolated nephrotic syndrome. Hantavirus is carried by rodents, and humans are typically infected through inhalation of aerosolised rodent excreta (urine, droppings, or saliva).

Answer 247

Mefenamic acid ## Footnote Mefenamic acid is the NSAID most likely to cause convulsions. Seizures occur in up to 10% of patients who overdose on NSAIDs, particularly with this drug.

Answer 248

Volume of distribution (Vd). ## Footnote Digoxin has a large volume of distribution, meaning it extensively distributes into tissues (e.g., heart, skeletal muscle, brain). A loading dose is needed to rapidly achieve therapeutic tissue levels, especially in acute situations.

Answer 249

Renal impairment and hypothyroidism. ## Footnote In these conditions, digoxin remains more in the plasma, increasing the risk of toxicity at standard doses.

Answer 250

Pelvic X-ray (to detect sacroiliitis - subchondral erosions, sclerosis) ## Footnote A pelvic X-ray focusing on the sacroiliac joints is the most sensitive and specific early radiological feature of AS. Sacroiliitis is often present early and supports diagnosis per modified New York criteria. Later features like bamboo spine develop much later in the disease course.

Answer 251

* miliary TB * sarcoidosis * HIV * lymphoma * very young age (e.g. < 6 months) ## Footnote Miliary TB represents disseminated TB. Despite heavy bacterial load, the immune system may be overwhelmed, resulting in anergy—a state where it fails to react to antigens, including tuberculin. Sarcoidosis is characterised by non-caseating granulomas and immune dysregulation. T-helper cell suppression can result in an impaired delayed hypersensitivity response, making the TST falsely negative. Lymphoma, particularly Hodgkin lymphoma, impairs cell-mediated immunity by disrupting lymphocyte function. This can result in an inadequate immune response to the tuberculin antigen, leading to false-negative results. TST depends on a functional cell-mediated immune response. HIV reduces CD4+ T cells, impairing the body's ability to mount a delayed hypersensitivity response to tuberculin. As a result, the test may be falsely negative even in individuals with TB.

Answer 252

IV ceftriaxone ## Footnote IV ceftriaxone is the empiric antibiotic of choice for bacterial meningitis in adults under 50 due to its excellent CNS penetration and activity against Neisseria meningitidis, a common cause in this age group. It is usually given IV twice daily. Benzylpenicillin may be given by GPs or paramedics before hospital transfer when meningococcal disease is suspected. However, in hospital, ceftriaxone or cefotaxime is preferred.

Answer 253

**haemochromatosis** hyperparathyroidism low magnesium, low phosphate acromegaly, Wilson's disease

Answer 254

JC virus ## Footnote A polyomavirus that remains latent and reactivates in immunosuppressed patients (e.g., HIV, transplant recipients).

Answer 255

CMV shows periventricular enhancement and ventriculitis ## Footnote Often with CD4 < 50; symptoms include confusion, lethargy, seizures.

Answer 256

Severe joint pain ## Footnote Chikungunya virus typically causes sudden-onset, intense polyarthralgia, especially affecting small joints like the hands, wrists, ankles, and feet. The pain is often debilitating and can persist for weeks or months, distinguishing it from other arboviral infections like dengue and Zika. The Chikungunya virus replicates in synovial and connective tissue, triggering a strong inflammatory response. This leads to synovitis and tenosynovitis, which manifest as pain, swelling, and stiffness in affected joints.

Answer 257

ELISA for Borrelia antibodies ## Footnote In patients with a suspicious history (e.g. tick bite, compatible symptoms) but no erythema migrans, the first-line investigation is an ELISA that detects IgM and IgG antibodies against Borrelia burgdorferi. A positive or equivocal result is followed by an immunoblot (Western blot) for confirmation. In the absence of erythema migrans or confirmed serology, antibiotics are not indicated. Starting treatment without diagnostic confirmation can lead to unnecessary medication use and confusion in follow-up. ELISA followed by immunoblot is the proper diagnostic pathway.

Answer 258

Gram-positive ## Footnote Exotoxins are primarily secreted by Gram-positive bacteria (e.g., Staphylococcus aureus, Clostridium spp., Corynebacterium diphtheriae), though some Gram-negative bacteria like Vibrio cholerae and E. coli also produce them.

Answer 259

Increases cAMP ## Footnote Cholera toxin ADP-ribosylates Gs proteins, activating adenylate cyclase, which raises cAMP levels in enterocytes. This leads to chloride and water secretion → profuse watery diarrhoea (rice-water stools).

Answer 260

No ## Footnote While local necrosis occurs (pseudomembrane in throat), diphtheria toxin inhibits elongation factor-2 (EF-2), blocking protein synthesis systemically. It can damage the heart (myocarditis) and nerves (neuropathy).

Answer 261

Tetanospasmin ## Footnote Clostridium tetani produces tetanospasmin, which blocks inhibitory neurotransmitters (GABA and glycine) in the CNS → sustained muscle contractions (spastic paralysis), including trismus ("lockjaw"). Botulinum toxin (from C. botulinum) does the opposite — it inhibits acetylcholine release, causing flaccid paralysis.

Answer 262

From 36 weeks gestation ## Footnote Starting suppressive aciclovir at 36 weeks reduces asymptomatic viral shedding and lowers the chance of neonatal HSV infection during delivery. Vaginal delivery is safe in recurrent HSV if there are no active lesions or symptoms during labor. Cesarean section is reserved for active outbreaks to prevent neonatal infection.

Answer 263

Oral metronidazole ## Footnote The first-line treatment is oral metronidazole. Options include: 2 g as a single dose, or 400–500 mg twice daily for 5–7 days. The longer course may be more effective in women. Sexual partners should also be treated to prevent reinfection.

Answer 264

External rotation ## Footnote External rotation is typically the first and most severely affected movement. Both active and passive range of motion are limited. Patients present with a stiff, painful shoulder, often worse at night. They commonly report difficulty with overhead activities, dressing, or doing up a bra. Pain progresses to stiffness over time. Unlike other causes (e.g., impingement, rotator cuff tear), adhesive capsulitis involves a global restriction of movement on both active and passive testing, especially in external rotation.

Answer 265

Painless and beefy red ## Footnote The ulcers are painless, bleed easily, and are typically described as "beefy red" due to their vascular granulation tissue. They can become extensive and destructive if untreated. Unlike syphilis (which usually presents with a single painless chancre), granuloma inguinale presents with multiple painless ulcers.

Answer 266

Haemophilus ducreyi (Chancroid)

Answer 267

* Hypodiplopy (<44 chromosomes) * FAB L3 type * T or B cell surface markers * Philadelphia translocation, t(9;22) * age < 2 years or > 10 years * male sex * CNS involvement * high initial WBC (e.g. > 100 * 109/l) * non-Caucasian

Answer 268

Eczema, thrombocytopenia, recurrent infections ## Footnote WAS presents with eczematous skin lesions, low platelet count (microthrombocytopenia), and increased susceptibility to infections due to combined B- and T-cell immunodeficiency.

Answer 269

Combined B- and T-cell immunodeficiency ## Footnote WAS leads to impaired humoral and cellular immunity, making patients susceptible to both bacterial and viral infections.

Answer 270

Hepatitis B ## Footnote Rituximab is a monoclonal antibody that binds to CD20, an antigen expressed on B cells. Depletion of B cells leads to an impaired humoral immune response, increasing the risk of Hepatitis B reactivation. Accordingly, Hepatitis B is routinely screened for in patients being considered for rituximab therapy due to the high risk of viral reactivation, with subsequent fulminant hepatitis and death. Current infection with Hepatitis B virus is considered a contraindication to rituximab therapy.

Answer 271

Gastrointestinal malignancy (especially gastric adenocarcinoma). In older adults, rapidly progressing AN with mucocutaneous involvement may be a paraneoplastic phenomenon.

Answer 272

CML ## Footnote CML typically presents with marked splenomegaly and significantly elevated WBC due to uncontrolled myeloid proliferation.

Answer 273

Friable cervix with contact bleeding and erosions ## Footnote A friable cervix that bleeds on contact and appears eroded is strongly suggestive of malignancy. In contrast, cervical ectropion may look red and inflamed but is not typically friable or ulcerated. When cervical cancer is suspected clinically (e.g., irregular bleeding, abnormal cervix), cytology is not sufficient. Colposcopy allows direct visualization and biopsy for histological diagnosis, which is essential for staging and treatment planning.

Answer 274

A full spectrum of granulocyte precursors: neutrophils, myelocytes, metamyelocytes, basophils, and blasts. ## Footnote The differential shows a "left shift" with predominance of immature myeloid cells and often basophilia.

Answer 275

Due to increased purine breakdown from high white cell turnover, leading to hyperuricaemia. ## Footnote Massive cell turnover results in uric acid accumulation, increasing the risk of gout.

Answer 276

Due to extramedullary haematopoiesis, sequestration of excess abnormal white cells, and direct infiltration by leukaemic cells. ## Footnote CML involves extramedullary haematopoiesis and rapid proliferation of myeloid cells, leading to significant spleen enlargement. In contrast, CLL involves slower lymphocytic infiltration without extramedullary haematopoiesis.

Answer 277

Nucleated red blood cells. ## Footnote In thalassaemia, ineffective erythropoiesis leads to early release of immature red cells (including nucleated forms) into the circulation. This, along with hypochromia and target cells, is a hallmark on peripheral smear.

Answer 278

Phenytoin can cause pancytopenia, including anemia, leukopenia, thrombocytopenia, and macrocytosis. ## Footnote Phenytoin may induce bone marrow suppression leading to decreased red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). It can also interfere with folate metabolism, causing macrocytic anemia (increased MCV).

Answer 279

Positive HBsAg, positive anti-HBc (total), negative IgM anti-HBc, negative anti-HBsAb, and detectable HBV DNA indicate chronic active infection.

Answer 280

Infection by the tapeworm Echinococcus granulosus. Humans acquire it through ingestion of parasite eggs from contaminated food, water, or soil, or contact with animal hosts.

Answer 281

Echinococcosis cysts present as cystic lesions on imaging with a long incubation period, while hepatocellular carcinoma is typically a solid mass in a cirrhotic liver with features of chronic liver disease and raised tumor markers.

Answer 282

Superficial branch of the radial nerve. ## Footnote The superficial branch of the radial nerve provides sensory innervation to the dorsal aspect of the first web space between the thumb and index finger. Loss of sensation in this area is a hallmark of radial nerve injury.

Answer 283

Extensor pollicis longus and brevis; posterior interosseous nerve. ## Footnote The posterior interosseous nerve, a motor branch of the radial nerve, innervates extensor pollicis longus and brevis, which are responsible for extending the thumb. Weakness in thumb extension suggests posterior interosseous nerve involvement.

Answer 284

Suggests posterior interosseous nerve involvement. ## Footnote Isolated weakness in thumb extension indicates dysfunction of the posterior interosseous nerve, a branch of the radial nerve, which can occur due to entrapment, trauma, or mononeuritis (e.g., in diabetes).

Answer 285

Pyoderma gangrenosum. ## Footnote Pyoderma gangrenosum (PG) is a neutrophilic dermatosis often associated with systemic disease, especially inflammatory bowel disease (IBD). It presents with rapidly progressing, painful ulcerative skin lesions, typically starting as pustules or nodules. PG lesions begin as papules or pustules that enlarge and ulcerate rapidly. The ulcers are painful, deep, often purulent, and have undermined, violaceous borders. Though classically on the legs, they can occur elsewhere.

Answer 286

Tuberculosis ## Footnote Erythema induratum is historically considered a tuberculid (hypersensitivity reaction to TB antigen), though many modern cases are not TB-related. It should prompt consideration of latent TB screening. Unlike erythema nodosum, which is septal panniculitis and usually non-ulcerative, erythema induratum is a lobular panniculitis with vasculitis that often ulcerates and scars. It more commonly affects the calves.

Answer 287

Insert a temporary pacemaker. ## Footnote In asymptomatic patients with complete heart block or AV dissociation, surgery carries a risk of haemodynamic instability due to intraoperative vagal tone. Temporary pacing allows surgery to proceed safely and can be followed by permanent pacing later if needed. Intraoperative increases in vagal tone or anaesthesia can worsen bradycardia in patients with AV block, potentially leading to hypotension, reduced cardiac output, and poor organ perfusion. Pre-emptive pacing prevents this.

Answer 288

Symptomatic bradycardia, complete heart block, overdrive pacing. ## Footnote Temporary pacing is used for: * Symptomatic bradycardia unresponsive to atropine * Complete heart block at risk of haemodynamic compromise * Suppression of tachyarrhythmias via overdrive pacing when drugs fail

Answer 289

Persistent or symptomatic AV block. ## Footnote Permanent pacemakers are used for: * Complete heart block * Mobitz type II block * Sick sinus syndrome * Drug-resistant tachyarrhythmias * Persistent AV block after MI * Trifascicular block with syncope or other AV block signs

Answer 290

Optic disc swelling. ## Footnote Optic disc swelling due to arteritic anterior ischaemic optic neuropathy (AION) is the most common cause of sudden visual loss in GCA. It results from occlusion of the posterior ciliary arteries supplying the optic nerve head. AION is caused by occlusion of the short posterior ciliary arteries due to vasculitis in GCA. It presents with sudden, painless, unilateral vision loss and optic disc swelling on fundoscopy.

Answer 291

Acute mitral regurgitation. ## Footnote Acute MR is a serious mechanical complication of MI, typically caused by papillary muscle or chordae tendineae rupture. It results in a loud pansystolic murmur (best heard at the apex), acute pulmonary oedema, and reduced forward cardiac output (e.g. low urine output).

Answer 292

X-linked adrenoleukodystrophy (ALD). ## Footnote ALD can mimic MS due to progressive sensory and motor dysfunction affecting the spinal cord and peripheral nerves. The adult form, adrenomyeloneuropathy, often presents with spastic paraparesis and neuropathy, leading to diagnostic confusion.

Answer 293

Elevated very long chain fatty acids (VLCFAs). ## Footnote X-linked ALD is due to mutations in the ABCD1 gene, leading to accumulation of VLCFAs in plasma and tissues, particularly affecting adrenal glands, CNS white matter, and peripheral nerves.

Answer 294

Pulmonary circulation. ## Footnote In the lungs, hypoxic pulmonary vasoconstriction occurs to divert blood away from poorly ventilated alveoli to better oxygenated regions. This optimizes the ventilation/perfusion (V/Q) ratio and enhances gas exchange.

Answer 295

Theophylline ## Footnote Theophylline stimulates the respiratory centre in the medulla, causing hyperventilation and resulting in respiratory alkalosis. It also causes tachycardia, tremor, and seizures in overdose.

Answer 296

Hypokalaemia. ## Footnote Theophylline causes intracellular shift of potassium, leading to low serum potassium. Treatment may require large doses of potassium supplementation.

Answer 297

Pityriasis lichenoides et varioliformis acuta (PLEVA). ## Footnote PLEVA presents with acute crops of erythematous papules, some of which develop necrotic or haemorrhagic crusts. Patients often describe a burning rather than itchy sensation. PLEVA is the acute, more severe end of the pityriasis lichenoides spectrum; pityriasis lichenoides chronica is the milder, chronic form with less inflammation and scaling.

Answer 298

Fabry disease, leading to disordered metabolism of sphingolipids

Answer 299

Automatic implantable cardioverter defibrillator (AICD). ## Footnote An AICD is indicated for secondary prevention in anyone who has had ventricular tachycardia or fibrillation with hemodynamic compromise. In HOCM, it significantly reduces the risk of sudden cardiac death (SCD).

Answer 300

Ventricular tachycardia (VT)

Answer 301

Decreased LDL receptor activity and clearance. ## Footnote In hypothyroidism, LDL receptor expression on hepatocytes is reduced, resulting in slower clearance of LDL cholesterol and elevated serum LDL levels.

Answer 302

Cushing's disease ## Footnote In Cushing's disease, which is caused by an ACTH-secreting pituitary adenoma, cortisol is not suppressed by low-dose dexamethasone (as seen with the 1mg test where cortisol remained elevated at 650 nmol/L) but is suppressed by high-dose dexamethasone (as demonstrated by the reduction to 220 nmol/L after the 8mg test). This suppression pattern occurs because the pituitary adenoma retains some sensitivity to negative feedback, but requires higher doses of glucocorticoids to achieve suppression. The elevated ACTH level (65 ng/L) confirms this is an ACTH-dependent form of Cushing's syndrome, consistent with Cushing's disease.

Answer 303

Left bundle branch block (LBBB)

Answer 304

Bisferiens pulse. ## Footnote A bisferiens pulse has two systolic peaks separated by a mid-systolic dip. It is classically seen in mixed aortic valve disease, especially when aortic regurgitation is significant alongside aortic stenosis.

Answer 305

Alternating strong and weak pulse beats, seen in severe LV systolic dysfunction. ## Footnote Although this patient has an LVEF of 40%, which is mildly reduced, pulsus alternans is more typical in advanced heart failure.

Answer 306

A drop in systolic BP >10 mmHg during inspiration; seen in cardiac tamponade and severe asthma. ## Footnote Pulsus paradoxus reflects exaggerated intrathoracic pressure effects, not valvular disease.

Answer 307

Hypokalaemia ## Footnote Digoxin normally binds to the ATPase pump on the same site as potassium. Hypokalaemia → digoxin more easily bind to the ATPase pump → increased inhibitory effects Think crisp packets (ie PKT) are always half-filled with air empty (ie MT) MT PKT (empty ie low) - Magnesium, Temp, pH, Potassium (k+), thyroid Fizzy drinks are always full (or high) and come in a CaN CaN - Calcium and Sodium (Na)

Answer 308

amyloid (most common), haemochromatosis, Loffler's syndrome, sarcoidosis, scleroderma

Answer 309

Mutations in the SCN5A gene (which encode the myocardial sodium ion channel protein)

Answer 310

Viridans streptococci e.g. Streptococcus sanguinis

Answer 311

Class IV: diffuse proliferative glomerulonephritis ## Footnote Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disease that can affect the kidneys, leading to lupus nephritis. According to the World Health Organisation (WHO) classification, Class IV or diffuse proliferative glomerulonephritis is the most common and severe form of lupus nephritis. It is characterised by diffuse global involvement (>50%) of glomeruli with endocapillary hypercellularity and subendothelial immune complex deposits.

Answer 312

* vasodilator: can decrease cardiac afterload * diuretic and natriuretic * suppresses both sympathetic tone and the renin-angiotensin-aldosterone system

Answer 313

repetitive and involuntary continuation of a response in the absence of the original stimulus ## Footnote Most commonly associated with lesions in the frontal lobe, specifically within the prefrontal cortex

Answer 314

A constellation of acalculia, right-left disorientation, finger agnosia and agraphia ## Footnote Affects the parietal lobe Gerstmann syndrome: Can’t count, can’t write, Can’t point, can’t right(-left) Dominant paRIGHTal lobe (opposite to handedness)

Answer 315

An anterior intracranial mass directly compresses the ipsilateral optic nerve --> atrophy and Increases intracranial pressure --> causing contralateral papilledema.

Answer 316

The inability to identify objects by touch, despite intact elementary tactile, proprioceptive, and thermal sensation. It occurs due to a lesion in the parietal lobe.

Answer 317

anterior spinal artery occlusion

Answer 318

Infarction of the left posterior cerebral artery affecting the splenium of the corpus callosum.

Answer 319

Lateral part of frontal lobe (inferior frontal gyrus)

Answer 320

A set of eye movement abnormalities due to a lesion in the dorsal midbrain — specifically around the tectal (pretectal) region.

Answer 321

Subthalamic nucleus of the basal ganglia

Answer 322

A rare autosomal recessive ciliopathy affecting multiple organ systems. ## Footnote Retinitis pigmentosa → progressive visual loss (night blindness first) Intellectual disability / developmental delay Hypogonadism (hypogonadotrophic) Renal anomalies (polycystic kidneys, dysplastic kidneys, renal failure) Polydactyly (extra fingers/toes — more in Bardet–Biedl form) Obesity (more marked in Bardet–Biedl form) Ataxia/spasticity (more in Laurence–Moon form)

Answer 323

A rare autosomal recessive disorder characterised by combined hearing loss and progressive vision loss due to retinitis pigmentosa.

Answer 324

head, arm, trunk = central lesion: stroke, syringomyelia just face = pre-ganglionic lesion: Pancoast's, cervical rib absent = post-ganglionic lesion: carotid artery

Answer 325

Medial longitudinal fasciculus

Answer 326

Transverse myelitis — inflammation of the spinal cord causing acute/subacute bilateral motor, sensory, and autonomic dysfunction.

Answer 327

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy ## Footnote Gene = NOTCH3 Presentation: Recurrent subcortical (lacunar) strokes in young adults (30s–50s) Migraine with aura (often early symptom) Progressive vascular dementia Mood disturbances (depression, apathy)

Answer 328

Amiodarone; Indomethacin

Answer 329

Ethambutol; Amiodarone; Metronidazole

Answer 330

Chloroquine; Quinine

Answer 331

Cinchonism

Answer 332

Tinnitus, flushing, and visual disturbances

Answer 333

Various ECG changes and hypotension

Answer 334

Metabolic acidosis and hypoglycaemia

Answer 335

Flash pulmonary oedema

Answer 336

Cyanide inhibits cytochrome c oxidase (Complex IV) in the mitochondrial electron transport chain, stopping oxidative phosphorylation and leading to impaired cellular oxygen utilization and lactic acidosis.

Answer 337

Brick-red skin, smell of bitter almonds, acute hypoxia, hypotension, headache, confusion; chronic features include ataxia, peripheral neuropathy, and dermatitis.

Answer 338

Bicuspid aortic valve

Answer 339

Necrolytic migratory erythema (NME), presenting as an annular, erythematous rash with scaling and crusting at the margins that migrates across the body.

Answer 340

Sensorineural deafness and congenital cataracts

Answer 341

Inhibits platelet aggregation

Answer 342

It typically correlates with **Lofgren's syndrome,** which is an acute form of sarcoidosis that generally resolves spontaneously within 2 years.

Answer 343

Hypercapnia causes a rightward shift of the oxygen dissociation curve by increasing hydrogen ion concentration (acidosis), which reduces haemoglobin's affinity for oxygen and enhances oxygen delivery to tissues.

Answer 344

Dyscrasias including folate deficiency and anaemia.

Answer 345

Morbiliform rash, Stevens-Johnson syndrome, acne, coarse features, and hirsutism.

Answer 346

Gingival hyperplasia.

Answer 347

Nystagmus, increased seizure frequency (overdose), movement disorders, cerebellar atrophy, mild peripheral neuropathy.

Answer 348

Hepatitis and phlebitis (with intravenous use).

Answer 349

Premature osteoporosis and osteomalacia.

Answer 350

Conduction abnormalities.

Answer 351

Marked lymphadenopathy ('pseudo lymphoma') and Dupuytren's contracture when severe.

Answer 352

Marked hypotension, especially postural (orthostatic) hypotension.

Answer 353

Syncope, dizziness, and other postural symptoms.

Answer 354

Benign prostatic hypertrophy (BPH).

Answer 355

Neuromuscular blocking agents e.g. vecuronium

Answer 356

Ophthalmoplegia Ataxia Areflexia NOTE: this is a variant of GBS and also often follows an infective illness

Answer 357

Ethanol or fomepizole (if mild-moderate) Haemodialysis (if severe) IV sodium bicarbonate for metabolic acidosis NOTE: severe is >30ml ingested, serum level >20mg/dl, visual complications, no improvement in acidosis despite sodium bicarbonate infusions

Answer 358

Depresses the eye and rotates it inward (intorsion).

Answer 359

Outward rotation with a torsional element to diplopia.

Answer 360

Loss of superior oblique function leads to misalignment, resulting in double vision with a torsional component.

Answer 361

Squamous-cell carcinoma (NOTE: small-cell carcinomas also occupy a central location, but without hypercalcaemia).

Answer 362

Prolactinoma — the combination of galactorrhoea and hypogonadotropic hypogonadism suggests this diagnosis.

Answer 363

A congenital posterolateral defect in the diaphragm, normally closed after fetal development; in adults, can serve as a communication pathway for ascitic fluid to pass from the peritoneal to the pleural cavity.

Answer 364

Wilson's disease is a rare autosomal recessive inborn error of copper metabolism, leading to copper deposition in tissues such as Descemet's membrane of the cornea (Kayser-Fleischer rings) and the liver (causing recurrent hepatitis). Both parents must be carriers but may be asymptomatic. It can cause type II (proximal) renal tubular acidosis, characterised by acidosis, hypokalaemia, and hypophosphataemia, with inability to acidify urine below pH 5.5 despite systemic acidosis, but with some ability to acidify urine distinguishing it from type I RTA.

Answer 365

Hypophosphataemia in type II RTA occurs due to impaired phosphate reabsorption in the proximal tubule, leading to phosphate wasting in urine.

Answer 366

Macrolides and quinolones are the antibiotics most likely to cause theophylline toxicity by inhibiting its metabolism. Quinolones also increase the risk of convulsions when used concurrently with theophylline.

Answer 367

Systemic lupus erythematosus (SLE) develops in around 93% of patients with homozygous C1q deficiency.

Answer 368

Complement activity helps clear circulating immune complexes; failure to clear them leads to tissue deposition and inflammation, triggering SLE.

Answer 369

Hypocomplementemic urticarial vasculitis (HUV), a rare autoimmune disease characterized by recurrent urticaria.

Answer 370

Diagnosis requires at least two of: venulitis on skin biopsy, arthritis, ocular inflammation, abdominal pain, or positive anti-C1q antibodies.

Answer 371

Up to 15% blood volume loss (approximately 750 ml); blood pressure is normal, and there may be slight tachycardia.

Answer 372

15-30% blood volume loss (750 ml to 1.5 L); systolic blood pressure usually normal; tachycardia is present.

Answer 373

30-40% blood volume loss (1.5-2 L); hypotension, tachycardia, and decreased urine output, but complete anuria is unlikely.

Answer 374

More than 40% blood volume loss (>2 L); severe shock with anuria.

Answer 375

Generalised muscle weakness.

Answer 376

IgM paraprotein.

Answer 377

An underlying lymphoproliferative disorder, specifically Waldenstrom's macroglobulinaemia.

Answer 378

Acute ST elevation of 1 mm or more in two or more contiguous limb leads, or 2 mm or more in two contiguous precordial leads.

Answer 379

Early repolarisation, pericarditis, left ventricular hypertrophy-related repolarisation abnormalities, or bundle branch block.

Answer 380

Enlarged left supraclavicular lymph node and mediastinal lymphadenopathy on chest X-ray.

Answer 381

The anterolateral thigh - due to entrapment of the lateral femoral cutaneous nerve (LFCN). Usually entrapped underneath or through the inguinal ligament, medial to the anterior superior iliac spine.

Answer 382

L2 and L3 nerve roots.

Answer 383

Purely sensory.

Answer 384

Obesity or weight gain leading to nerve compression.

Answer 385

It blocks the release of acetylcholine from the motor nerve terminal (presynaptic disorder).

Answer 386

Blurred vision, dysphagia, and dysarthria.

Answer 387

Impaired pupillary light responses, reduced tendon reflexes, and progressive symmetrical limb weakness.

Answer 388

Dry mouth, constipation, and urinary retention.

Answer 389

A decremental response on repetitive nerve stimulation.

Answer 390

Motor nerves, especially in the upper limbs, with possible peroneal nerve involvement causing foot drop. Note: No sensory involvement

Answer 391

Segmental demyelination and axonal degeneration due to mitochondrial interference and impaired neurotransmitter release.

Answer 392

Behavioural changes and abdominal pain.

Answer 393

Manganese.

Answer 394

Increased frequency of HLA-DR2 and HLA-DR3.

Answer 395

PaO2 < 7.3 kPa, FEV1 ≤ 1.5 L, and FVC < 21 L despite maximal treatment, stable on two occasions >3 weeks apart, in clinically stable non-smokers.

Answer 396

In patients with pulmonary hypertension showing right ventricular hypertrophy, a loud S2, and features of cor pulmonale. NOTE: Cor pulmonale in the absence of hypoxia may have a primary cardiological underlying cause and therefore may not require home oxygen therapy.

Answer 397

Tobacco use up-regulates hepatic enzymes, increasing metabolism and lowering theophylline levels.

Answer 398

Heart failure, liver cirrhosis, acute viral infection, increased age, drugs that inhibit metabolism (e.g., erythromycin), and cessation of enzyme-inducing drugs.

Answer 399

Septal wall thickness greater than 3 cm

Answer 400

A, D, E, K

Answer 401

Standard error of the mean = standard deviation / square root (number of patients)

Answer 402

C1q, C1rs, C2, C4 ## Footnote These proteins are part of the classical pathway of the complement system. Deficiencies in these components predispose to immune complex diseases like systemic lupus erythematosus (SLE), because they play a crucial role in the clearance of immune complexes and apoptotic cells. If these proteins are deficient, there will be an accumulation of immune complexes which can deposit in tissues causing inflammation and damage.

Answer 403

Pulmonary vasodilation via increased cyclic GMP Leads to: vasodilation + inhibits platelet aggregation

Answer 404

Nondisjunction ## Footnote Nondisjunction occurs during meiosis (typically maternal meiosis I) when homologous chromosomes fail to separate properly, resulting in an egg cell with 24 chromosomes instead of 23. When this egg is fertilised by a normal sperm with 23 chromosomes, the resulting zygote has 47 chromosomes, including three copies of chromosome 21 (trisomy 21). This is why Down's syndrome is also known as trisomy 21. The risk of nondisjunction increases with maternal age, which explains the higher incidence of Down's syndrome in children born to older mothers.

Answer 405

An increased risk of aortic dilatation and dissection

Answer 406

Adipose tissue ## Footnote Leptin is a hormone secreted primarily by adipose tissue in proportion to fat mass. In the scenario, appetite suppression and weight loss were observed following stimulation of a hormone that naturally reduces appetite — this corresponds to leptin. Leptin acts on the hypothalamus to inhibit hunger and promote energy expenditure. The patient's obesity implies leptin resistance, a common feature in individuals with high adiposity, which the drug may be aiming to overcome by enhancing leptin signalling. Therefore, the hormone responsible for this effect is secreted by adipose tissue.

Answer 407

Hypokalaemia and hyponatraemia.

Answer 408

Orbital apex syndrome.

Answer 409

Cranial nerve VI (abducens nerve) palsy.

Answer 410

The first branch (ophthalmic branch) of the trigeminal nerve.

Answer 411

The tibial nerve and the common peroneal nerve.

Answer 412

Foot drop.

Answer 413

Diffuse muscle atrophy begins in the hands and spreads proximally, eventually involving the shoulder girdle.

Answer 414

Increased tone that may progress to spastic paraparesis.

Answer 415

The dose is usually halved.

Answer 416

Because its pharmacokinetics are minimally affected and it does not interact with carbamazepine.

Answer 417

Up to 500 mg/day if required. Half life: 22 hours

Answer 418

Because free phenytoin levels may be high despite total plasma levels being in range.

Answer 419

Palpable cysts that can appear radioopaque on plain X-ray.

Answer 420

Adult-onset focal epilepsy, especially in endemic areas.

Answer 421

Myoclonic seizures, often associated with generalised tonic-clonic seizures and sometimes absence seizures.

Answer 422

Seizures occur almost exclusively on or soon after awakening, either from all-night sleep or from a nap.

Answer 423

Levetiracetam.

Answer 424

At least two of the following: (1) ≥6 café-au-lait spots ≥5 mm in pre-pubertal or ≥15 mm in post-pubertal individuals, (2) ≥2 neurofibromas of any type or 1 plexiform neurofibroma, (3) axillary or inguinal freckles, (4) ≥2 iris hamartomas (Lisch nodules), (5) optic nerve glioma, (6) sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis.

Answer 425

Their presence on slit-lamp examination allows a positive clinical diagnosis of NF1 without further investigation.

Answer 426

Airway intubation and ventilation to control BP, reduce myocardial ischaemia risk, and manage seizures.

Answer 427

It can lead to rhabdomyolysis and acute kidney injury.

Answer 428

Those with a life expectancy of less than ten years or aged over 75 years.

Answer 429

Child-Pugh score C.

Answer 430

IV 3rd-generation cephalosporin plus metronidazole.

Answer 431

It is a key determinant of disease progression, contributing to lung damage.

Answer 432

It occurs early in the disease.

Answer 433

It is the antigen-binding fragment that binds to antigens.

Answer 434

It is the fragment crystallisable region that interacts with cell surface receptors.

Answer 435

Pulmonary arteries ## Footnote Pulmonary arteries are unique in their response to hypoxia. Unlike systemic vasculature, which dilates in response to hypoxia, pulmonary arteries constrict. This phenomenon, known as hypoxic pulmonary vasoconstriction (HPV), is a physiological response that diverts blood from poorly ventilated areas of the lung to better ventilated areas, optimising gas exchange and maintaining oxygen delivery to the tissues.

Answer 436

It indicates how much the odds of the disease decrease when a test is negative.

Answer 437

dipalmitoyl phosphatidylcholine (DPPC) ## Footnote DPPC is a phospholipid that forms a surface-active monolayer at the air-liquid interface of the alveoli, reducing surface tension and preventing alveolar collapse during expiration. Its unique molecular structure, with two saturated palmitic acid chains, allows for optimal surface tension-lowering properties at body temperature. 28 palm oil trees (first detectable at 28 weeks - dipalmtoyl rhymes with palm oil)

Answer 438

In the Purkinje fibres ## Footnote Purkinje fibres are of large diameter and achieve velocities of 2-4 m/s, the fastest conduction in the heart. This rapid conduction allows coordinated ventricular contraction.

Answer 439

Diagnosis is confirmed by muscle biopsy which is characteristic with 'ragged red fibres'

Answer 440

The proportion of individuals who carry a disease-causing allele and express the related disease phenotype.

Answer 441

Increased, due to defective proximal tubular phosphate reabsorption.

Answer 442

Plasma cells.

Answer 443

Pearson's product-moment correlation coefficient.

Answer 444

-1 = perfect negative correlation, 0 = no correlation, 1 = perfect positive correlation.

Answer 445

Chi-squared test.

Answer 446

Spearman's rank correlation coefficient.

Answer 447

Paired compares two measurements from the same group (before/after); unpaired compares measurements from two different groups.

Answer 448

Wilcoxon signed-rank test.

Answer 449

CER = Number of events in control group ÷ Number of participants in control group.

Answer 450

EER = Number of events in experimental group ÷ Number of participants in experimental group.

Answer 451

ARR = Control Event Rate (CER) − Experimental Event Rate (EER).

Answer 452

NNT = 1 ÷ ARR.

Answer 453

Endothelin causes potent pulmonary vasoconstriction. Endothelin receptor antagonists (e.g., bosentan, ambrisentan) are used in primary pulmonary hypertension to reduce this vasoconstriction and improve pulmonary haemodynamics.

Answer 454

11-Deoxycortisol

Answer 455

Mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene

Answer 456

Advancing parental age at conception

Answer 457

Rhizomelia (short proximal limbs) with brachydactyly

Answer 458

Large head with frontal bossing and narrow foramen magnum

Answer 459

Midface hypoplasia with flattened nasal bridge

Answer 460

Hands with short fingers and separation between the middle and ring fingers

Answer 461

Lumbar lordosis

Answer 462

Supportive management; limb lengthening procedures in selected cases

Answer 463

Ilizarov frames

Answer 464

Pemphigoid gestationis

Answer 465

Linear C3 deposition at the dermoepidermal junction on perilesional skin biopsy

Answer 466

Type II hypersensitivity reaction against hemidesmosomal proteins

Answer 467

Avocado, banana, kiwi fruit, and chestnut

Answer 468

Often asymptomatic; recurrent respiratory or gastrointestinal infections; allergic and autoimmune diseases; anaphylaxis to blood products containing IgA

Answer 469

They may develop anti-IgA antibodies that trigger anaphylaxis upon exposure to IgA in donor blood products

Answer 470

M-protein < 3 g/dL, < 10% monoclonal plasma cells in bone marrow, no end-organ damage (no CRAB features)

Answer 471

~1% per year

Answer 472

Asymptomatic, often incidental finding on serum protein electrophoresis

Answer 473

1 molecule of C1q, 2 molecules of C1r, and 2 molecules of C1s.

Answer 474

C1q binding to IgM or IgG that is complexed with antigen.

Answer 475

Formation of the membrane attack complex (MAC), leading to cell lysis.

Answer 476

A key cytokine in the acute phase response, mainly produced by activated monocyte-phagocytic cells, and to a lesser extent by antigen-stimulated T-cells, NK cells, and activated mast cells.

Answer 477

Stimulates release of corticotrophin releasing hormone from the hypothalamus, increasing cortisol secretion from the adrenal glands.

Answer 478

Angiogenesis, appetite suppression via leptin, increased insulin resistance via phosphorylation of insulin receptors, recruitment of neutrophils, prostaglandin release causing fever.

Answer 479

Low cholesterol levels — in protein-losing enteropathy, protein leakage is independent of molecular weight, unlike in nephrotic syndrome where protein loss leads to increased cholesterol.

Answer 480

In glomerulopathies, protein loss depends on molecular weight and charge; in protein-losing enteropathy, it is independent of molecular weight.

Answer 481

Mycophenolate — an anti-purine drug that selectively depletes activated B and T lymphocytes, with neutropenia being rare.

Answer 482

It targets activated B and T cells while sparing neutrophils, making neutropenia uncommon.

Answer 483

C4 deficiency — along with C1q, C1r, or C1s deficiencies, it is a strong risk factor for early-onset lupus.

Answer 484

C1q, C1r, C1s (strong association); C2 deficiency also increases risk but with a typical age/sex pattern like non-complement SLE.

Answer 485

Rare inherited autoinflammatory disorders with short, recurrent episodes of fever and severe localised inflammation, occurring periodically or irregularly, and not due to usual infections.

Answer 486

They lack high-titre autoantibodies and antigen-specific T-cells — hence classified as autoinflammatory rather than autoimmune.

Answer 487

Familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), and hyper IgD syndrome.

Answer 488

Detoxification of deoxyadenosine, which normally is converted to deoxynosine by ADA.

Answer 489

Build-up of deoxyadenosine is toxic to lymphocytes, especially immature T cells in the thymus.

Answer 490

Marked reduction in lymphocyte numbers, leading to severe combined immunodeficiency (SCID).

Answer 491

A condition with selective loss of subcutaneous fat from the face, upper arms, and trunk, often post-viral illness.

Answer 492

C3 nephritic factor.

Answer 493

Membranoproliferative glomerulonephritis and autoimmune disorders.

Answer 494

Orientia tsutsugamushi - characteristic skin finding: a black eschar at the site of the bite.

Answer 495

By larval mites known as chiggers.

Answer 496

Doxycycline.

Answer 497

Northern Australia (bush areas).

Answer 498

H. pylori gastritis contains the clonal B-cells that can give rise to MALT lymphoma.

Answer 499

Yes — some regress with H. pylori eradication alone.

Answer 500

Eradication of H. pylori using appropriate antibiotic therapy.

Answer 501

Darier's disease (keratosis follicularis).

Answer 502

Acantholysis with dyskeratosis.

Answer 503

Zollinger-Ellison syndrome.

Answer 504

Serum gastrin levels.

Answer 505

Multiple endocrine neoplasia type 1 (MEN-1).

Answer 506

Because it is more likely caused by excessive gastric acid secretion from the gastrinoma rather than small bowel pathology.

Answer 507

In parenchymal cells, such as hepatocytes.

Answer 508

Liver biopsy demonstrating parenchymal iron deposition and assessment of liver damage.

Answer 509

Due to absolute insulinopaenia or increased insulin resistance, which impairs lipid metabolism.

Answer 510

By controlling hyperglycaemia to achieve target HbA1c, which can significantly reduce triglyceride levels.

Answer 511

Hypertriglyceridaemia, elevated AST, and elevated gamma-glutamyltransferase (GGT) activity.

Answer 512

Deficient activity of acid beta-glucosidase, leading to accumulation of glucocerebroside in cells of the macrophage-monocyte system.

Answer 513

Non-neuropathic, acute neuropathic, and chronic neuropathic.

Answer 514

Acid phosphatase and angiotensin-converting enzyme (ACE).

Answer 515

Recombinant glucosidase enzyme replacement and glucosylceramide inhibitors (e.g., miglustat).

Answer 516

Fasting plasma glucose <7.0 mmol/L and 2-hour plasma glucose ≥7.8 mmol/L but <11.1 mmol/L during OGTT.

Answer 517

Fasting plasma glucose between 6.1 and 6.9 mmol/L.

Answer 518

No — fasting glucose is 5.6 mmol/L, which is below the impaired fasting glucose range.

Answer 519

Synthesised in the liver; carry most of the body's triglycerides and a smaller amount of cholesterol.

Answer 520

They provide the main source of energy during prolonged fasting.

Answer 521

Apolipoprotein C-II; it allows VLDL to bind to capillary endothelium and enables triglyceride removal by lipoprotein lipase.

Answer 522

It becomes an intermediate-density lipoprotein (IDL) particle, depleted of triglyceride and apolipoprotein C-II.

Answer 523

Pheochromocytomas, renal cell carcinoma, pancreatic cysts, CNS hemangioblastomas.

Answer 524

Bilateral epididymal cystadenomas in men, broad ligament cystadenomas in women, and haemangiomas.

Answer 525

Neurofibromatosis type 1 and Multiple Endocrine Neoplasia type 2 (MEN2).

Answer 526

No — MEN1 is associated with pancreatic tumors, parathyroid hyperplasia/adenomas, and pituitary tumors, not pheochromocytomas.

Answer 527

In the brain, it responds to glucose levels; in the liver, activity increases after meals.

Answer 528

By binding to glucokinase regulatory protein (GKRP), which represses its activity.

Answer 529

Co-repression.

Answer 530

Insulin upregulates glucokinase production via SREBP1c.

Answer 531

Loss-of-function mutations in the glucokinase (GCK) gene.

Answer 532

Stereoisomerism is a property where molecules (or enzymes) have the same molecular formula but differ in the spatial arrangement of atoms, potentially affecting activity.

Answer 533

Affinity refers to the strength of binding between an enzyme and its substrate.

Answer 534

Co-activation is a regulatory mechanism where the presence of a co-factor or molecule increases the activity of an enzyme.

Answer 535

Co-repression is a regulatory mechanism where binding of a molecule or protein reduces or represses enzyme activity.

Answer 536

Autosomal dominant.

Answer 537

A genetic disorder characterised by multiple telangiectasias and arteriovenous malformations, leading to recurrent bleeding.

Answer 538

Osler-Weber-Rendu syndrome.

Answer 539

Recurrent epistaxis, telangiectasias around the nose and mouth, gastrointestinal haemorrhage, and possible cerebral haemorrhage.

Answer 540

Porphyria cutanea tarda (PCT).

Answer 541

Uroporphyrinogen decarboxylase.

Answer 542

Alcoholism, iron overload, estrogens, hepatitis C infection, and certain medications.

Answer 543

Acute intermittent porphyria (AIP).

Answer 544

Congenital erythropoietic porphyria (CEP).

Answer 545

Aortic valve incompetence, often secondary to aortic root dilatation.

Answer 546

Fibrillin-1 (FBN1) gene on chromosome 15q21.

Answer 547

Pectus carinatum, marked pectus excavatum, reduced upper-to-lower segment ratio <0.85, arm span to height ratio >1.05, positive thumb/wrist signs (Steinberg/Walker-Murdoch), thoracolumbar scoliosis >20°, progressive collapsing foot deformity, protrusio acetabula.

Answer 548

At least two major criteria, or one major plus two minor criteria.

Answer 549

Lens dislocation (ectopia lentis), usually upwards, found in 50-80% of patients.

Answer 550

Medullary thyroid carcinoma.

Answer 551

Defect in nucleotide excision repair (NER), leading to impaired repair of UV-induced DNA damage.

Answer 552

Photosensitivity, severe sunburn in infancy, freckle-like pigmented spots, atrophic lesions with telangiectasia, multiple solar keratoses, early onset skin cancers, and possible ophthalmic and neurological abnormalities.

Answer 553

Alpha-1 antitrypsin deficiency (A1AD).

Answer 554

Decreased alpha-1 antitrypsin activity leading to increased risk of emphysema and liver disease due to accumulation of abnormal protein in hepatocytes.

Answer 555

PLOD1 gene → encodes lysyl hydroxylase 1.It hydroxylates lysine residues in collagen to form hydroxylysine.

Answer 556

It is commonly found in collagen and is essential for proper collagen cross-linking.

Answer 557

Defective collagen leading to kyphoscoliosis-type Ehlers-Danlos syndrome.

Answer 558

Homocystinuria.

Answer 559

Cystathionine beta-synthase (CBS).

Answer 560

Elevated homocysteine and methionine in blood and urine.

Answer 561

Pyridoxine (vitamin B6), folic acid, vitamin B12 supplementation, and methionine-restricted diet.

Answer 562

Premature atherosclerosis and thromboembolic events.

Answer 563

KAL1 gene mutation affecting GnRH neuron migration.

Answer 564

Human chorionic gonadotrophin (hCG) or testosterone therapy.

Answer 565

Ciprofloxacin.

Answer 566

Fibrates are PPAR-α agonists that predominantly reduce serum triglycerides and increase HDL-cholesterol by upregulating gene transcription.

Answer 567

Methaemoglobinaemia results from oxidation of ferrous iron (Fe²⁺) in hemoglobin to ferric iron (Fe³⁺), leading to Heinz body formation and possible haemolytic anaemia. Nitrates, including amyl nitrate, can trigger this reaction.

Answer 568

Intravenous sodium bicarbonate is the most effective treatment because it ionises circulating aspirin, reducing tissue penetration and enhancing renal elimination. Supportive measures include hydration, electrolyte correction, and activated charcoal to reduce absorption.

Answer 569

Sildenafil citrate is a potent and selective inhibitor of type-V phosphodiesterase, preventing the breakdown of cyclic guanosine monophosphate (cGMP) and promoting nitric oxide-mediated vasodilation of penile arterioles.

Answer 570

Headache, flushing, dyspepsia, nasal congestion, and in a small percentage (2-3%), altered colour vision (blue halo), visual brightness changes, or blurred vision.

Answer 571

Respiratory alkalosis due to direct stimulation of the respiratory centre, causing hyperventilation before any metabolic acidosis develops.

Answer 572

Cisapride is a prokinetic drug that increases the motility of the entire gastrointestinal tract and enhances gastric emptying, reducing gastric emptying time.

Answer 573

Cisapride interacts with anticoagulants, increasing prothrombin time and bleeding risk, and with enzyme inhibitors like erythromycin or ketoconazole, increasing the risk of QT prolongation and arrhythmias.

Answer 574

Cisapride can cause QT interval abnormalities and has been associated with fatal arrhythmias, particularly when combined with certain enzyme-inhibiting drugs.

Answer 575

Anticholinergics.

Answer 576

Oral activated charcoal adsorbs many drugs and complex chemicals, reducing their absorption from the gastrointestinal tract and interrupting enterohepatic recirculation.

Answer 577

It should only be given to patients who are able to protect their airway to avoid risk of aspiration.

Answer 578

Absence of bowel sounds may indicate paralytic ileus, which increases the risk of charcoal aspiration and pneumonitis.

Answer 579

Ondansetron is a selective 5-HT3 receptor antagonist that blocks serotonin-mediated stimulation of vagal afferents in the gut and central neurons in the chemoreceptor trigger zone, preventing chemotherapy-induced nausea and vomiting.

Answer 580

Chemotherapy causes the release of serotonin from enterochromaffin cells in the small intestine, which stimulates 5-HT3 receptors on vagal afferents and triggers the vomiting reflex.

Answer 581

Ondansetron acts on 5-HT3 receptors both peripherally on vagal afferents and centrally in the chemoreceptor trigger zone in the area postrema.

Answer 582

The absence of isotype suppression — with normal IgG and IgA levels — would be more suggestive of Waldenström’s macroglobulinaemia, as isotype suppression is more typical of myeloma.

Answer 583

A reduction in the levels of other immunoglobulin classes (e.g., IgG, IgA) due to clonal proliferation of one immunoglobulin type. Seen in myeloma, but not Waldenstrom’s

Answer 584

Paraquat reacts with oxygen to produce hydrogen peroxide and superoxide, causing oxidative tissue injury, inflammation, and acute alveolitis. The lungs are the most affected organ — paraquat is sequestered in pulmonary tissue, leading to acute alveolitis and later pulmonary fibrosis.

Answer 585

Respiratory failure within hours to days due to acute lung injury.

Answer 586

Pulmonary fibrosis, which may develop up to 6 weeks after ingestion.

Answer 587

Corrosive effects on the gastrointestinal tract and oropharynx, such as pain, ulceration, and dysphagia. Remember: The lungs are the most affected organ — paraquat is sequestered in pulmonary tissue, leading to acute alveolitis and later pulmonary fibrosis.

Answer 588

Primary hyperparathyroidism, seen in about 90% of patients by age 65.

Answer 589

The Menin gene.

Answer 590

Granulomatosis with polyangiitis (GPA).

Answer 591

Minimal or absent immune complex deposition on immunohistochemistry despite active inflammation.

Answer 592

SLE shows abundant immune complex deposition, while GPA is pauci-immune.

Answer 593

Mesangial IgA deposition.

Answer 594

Linear IgG deposition along the glomerular basement membrane.

Answer 595

IgA nephropathy; mesangial IgA deposition.

Answer 596

It inhibits CYP1A2, reducing warfarin metabolism and increasing its plasma concentration.

Answer 597

It raises INR and increases the risk of bleeding.

Answer 598

"Upper trunk of the brachial plexus (C5-C6), causing Erb’s palsy."

Answer 599

"Weakness in shoulder abduction (deltoid, supraspinatus), external rotation (infraspinatus, teres minor), and elbow flexion (biceps, brachialis)."

Answer 600

"Loss of sensation over the lateral aspect of the upper arm and forearm (C5–C6 dermatomes)."

Answer 601

"Beta-hydroxybutyrate"

Answer 602

"Because the altered redox state in DKA (increased NADH/NAD+ ratio) favours conversion of acetoacetate to beta-hydroxybutyrate."

Answer 603

"Beta-hydroxybutyrate persists longer than acetoacetate/acetone due to slower metabolism, contributing to lingering acidaemia."

Answer 604

"Beta-hydroxybutyrate (major), acetoacetate, and acetone (minor)."

Answer 605

Logistic regression (with time off work as outcome and symptoms as predictors).

Answer 606

Because Cox regression is designed for time-to-event data and correctly handles censored cases (patients not yet returned to work at study end).

Answer 607

They estimate the relative weight of each symptom in predicting time off work (e.g. a coefficient twice as large indicates double the predictive weight).

Answer 608

It is positively charged externally - At rest, the neuronal membrane is far more permeable to K⁺ than to Na⁺. The inside of the neurone is relatively negative, containing more K⁺ and Cl⁻, while the outside is positive, rich in Na⁺. This establishes the resting membrane potential(polarised state).

Answer 609

It cleaves enamel matrix proteins and influences enamel thickness and mineralisation.

Answer 610

MMP28; it is thought to degrade casein and contribute to tissue homeostasis and wound repair.

Answer 611

MMP3, MMP10, and MMP11; they degrade collagen subtypes, proteoglycans, fibronectin, laminin, and elastin.

Answer 612

Up to 12 months; tensile strength of the wound increases and random collagen is replaced by organised collagen aligned along lines of stress.

Answer 613

Lasts up to 3 days; platelets aggregate and release enzymes, ATP, serotonin, and cytokines; fibrin clot forms to complete haemostasis; surface dries to form a scab; vasodilatation occurs due to platelet and macrophage factors, leading to warmth, swelling, and accumulation of serum and white blood cells.

Answer 614

Macrophages remove fibrin, dead cells, and bacteria, create spaces for granulation tissue, release factors that stimulate new capillary buds, and later initiate and control fibroblast activity for repair; random collagen deposition begins after a few days, peaking at 5–7 days.

Answer 615

Hepatic stellate (Ito) cells, which reside in the space of Disse, transform into myofibroblasts in response to mediators like TGF-β, producing extracellular matrix components (collagen I, III, IV, fibronectin, laminin, chondroitin sulfate, hyaluronic acid) and controlling sinusoidal perfusion via cytoskeletal actin.

Answer 616

Cellular senescence defined by arrest of mitosis. It is a state in which cells permanently stop dividing, typically after around 50 divisions (Hayflick limit), caused by telomeric shortening, DNA damage at telomeric and non-telomeric sites, and other stressors that trigger a DNA damage response. Cells that escape senescence may become cancerous.

Answer 617

Kupffer cells are liver macrophages that produce mediators stimulating stellate cells, but they do not directly cause fibrogenesis.

Answer 618

Bile duct epithelial cells are involved in diseases like primary biliary cholangitis and primary sclerosing cholangitis, but they are not a primary driver of alcoholic cirrhosis fibrosis.

Answer 619

Liver sinusoidal endothelial cells contribute to liver regeneration after injury but do not drive fibrosis.

Answer 620

Fatty acid oxidation via beta-oxidation in mitochondria, producing acetyl-CoA for the TCA cycle and generating large amounts of ATP.

Answer 621

Autoantibodies target cadherins (desmoglein-3), disrupting desmosomal adherent junctions between keratinocytes and causing intraepidermal blister formation.

Answer 622

The major concern is ensuring that only the target cells are transplanted, because if other cells are included they may continue to divide and form a mass within the device.

Answer 623

Squamous cell cancers (lung, head and neck, cervical, vulvar), ovarian, breast, kidney cancers, pancreatic islet cell tumours, pheochromocytomas, and some haematological malignancies.

Answer 624

Flexor digitorum superficialis (FDS), supplied by the median nerve.

Answer 625

Hyaline cartilage is avascular and receives nutrients via diffusion from synovial fluid.

Answer 626

P-glycoprotein, an ATP-dependent drug efflux transporter encoded by the MDR1 gene, reduces intracellular concentrations of cytotoxic drugs and decreases chemotherapy efficacy.

Answer 627

≥ 7.0 mmol/L (126 mg/dL); patient must fast ≥8 hours; repeat test to confirm unless symptomatic

Answer 628

≥ 11.1 mmol/L (200 mg/dL); repeat not always required if symptomatic (polyuria, polydipsia, weight loss)

Answer 629

≥ 11.1 mmol/L (200 mg/dL) after a 75 g glucose load

Answer 630

≥ 48 mmol/mol (6.5%); repeat required unless patient has classic hyperglycemic symptoms; unreliable in hemoglobinopathies or anemia

Answer 631

6.1–6.9 mmol/L (110–125 mg/dL); indicates increased risk, lifestyle modification recommended

Answer 632

7.8–11.0 mmol/L (140–199 mg/dL); indicates increased risk, often detected via OGTT

Answer 633

≥ 5.6 mmol/L; screen high-risk women at 24–28 weeks (BMI ≥30, previous GDM, macrosomic baby, family history)

Answer 634

≥ 7.8 mmol/L; screen high-risk women at 24–28 weeks

Answer 635

Cystathionine synthase deficiency.

Answer 636

Type 2 is caused by methionine synthase deficiency. Key features include elevated homocysteine, megaloblastic anemia, developmental delay, and often responds to vitamin B12.

Answer 637

Type 3 is caused by methylenetetrahydrofolate reductase (MTHFR) deficiency. Key features include elevated homocysteine with normal methionine, variable neurological deficits, and may respond to folate and vitamin B12 supplementation.

Answer 638

Thickens cervical mucus, preventing sperm entry. The progesterone-only pill does reduce tubal motility, but this is most important as a risk factor for ectopic pregnancy.

Answer 639

Nicorandil activates ATP-dependent potassium channels, causing venous smooth muscle relaxation (reduced ventricular filling pressures) and coronary arteriole dilatation. Adverse effects include headache (~35%), oral ulceration, flushing, and gastrointestinal disturbance.

Answer 640

Ciprofloxacin inhibits bacterial DNA gyrase, preventing DNA replication and transcription.

Answer 641

In Cushing’s disease (pituitary-dependent), there is incomplete suppression of cortisol with high-dose dexamethasone and an increase in cortisol after CRH. In ectopic ACTH or adrenal tumors, there is typically no suppression with dexamethasone and no response to CRH.

Answer 642

COL4A5 mutation (X-linked Alport Syndrome). Mutations in type IV collagen cause defects in the glomerular basement membrane, cochlea, and lens, explaining haematuria, sensorineural hearing loss, and ocular abnormalities. X-linked inheritance is suggested by affected male relatives and early progression to renal failure.

Answer 643

"COL4A5 mutation

Answer 644

"Haematuria

Answer 645

"COL4A3 or COL4A4 (homozygous or compound heterozygous) → Presents earlier

Answer 646

"COL4A3 or COL4A4 (heterozygous) → Presents with persistent haematuria

Answer 647

"Subepithelial layer → tense blisters. Mucous membranes are usually spared."

Answer 648

"Conjunctiva"

Answer 649

"Peripheral chemoreceptors (carotid bodies > aortic bodies)"

Answer 650

"Central chemoreceptors responding to PaCO2"

Answer 651

"CO2 crosses BBB → forms H+ in CSF → detected by central chemoreceptors"

Answer 652

"Rises immediately post-injury

Answer 653

Posterior inferior cerebellar artery (PICA)

Answer 654

Ipsilateral facial pain/temp loss, contralateral body pain/temp loss, ipsilateral cerebellar ataxia, ipsilateral Horner syndrome

Answer 655

The organ of Corti, which produces nerve impulses in response to sound vibrations

Answer 656

Central pontine myelinolysis

Answer 657

Loss of water due to extracellular hypertonicity after rapid sodium correction

Answer 658

Lateral nucleus → hunger/feeding centre. Mnemonic: Lateral = Love food

Answer 659

Anorexia/starvation

Answer 660

Ventromedial nucleus (VMN) → satiety centre. Mnemonic: VentroMedial = Very Minimal eating

Answer 661

Hyperphagia/obesity

Answer 662

Supraoptic nucleus. Mnemonic: Supra = Sips water (ADH saves water)

Answer 663

Paraventricular nucleus. Mnemonic: Para = Parent hormones

Answer 664

Anterior nucleus (preoptic). Mnemonic: A/C = Anterior Cooling

Answer 665

Hyperthermia

Answer 666

Posterior nucleus. Mnemonic: Posterior = Heating (hot posterior)

Answer 667

Hypothermia

Answer 668

Suprachiasmatic nucleus (SCN). Mnemonic: SCN = Sun Cycle Nucleus

Answer 669

Arcuate nucleus. Mnemonic: Arcuate = Arches dopamine

Answer 670

Mammillary bodies. Mnemonic: Mammillary = Memory

Answer 671

Wernicke–Korsakoff syndrome (confusion, ataxia, ophthalmoplegia, memory loss)

Answer 672

More than one episode; potential treatment: radiofrequency ablation

Answer 673

More than one episode; potential treatment: radiofrequency ablation

Answer 674

Highly symptomatic, refractory to, or intolerant of drugs; potential treatment: radiofrequency ablation therapy

Answer 675

Unless there is an obvious reversible cause, e.g., STEMI; potential treatment: implantable cardioverter-defibrillator (ICD)

Answer 676

Unless there is an obvious reversible cause; potential treatment: ICD or radiofrequency ablation

Answer 677

Ejection fraction >30% on optimal medical therapy; potential treatment: primary prevention ICD

Answer 678

QRS >130 ms, on optimal medical therapy, ejection fraction <35%; potential treatment: heart failure pacing

Answer 679

Inhibition of the hepatic uptake transporter OATP1B1 by ciclosporin, leading to elevated rosuvastatin levels

Answer 680

Ciclosporin, gemfibrozil, some macrolides, protease inhibitors

Answer 681

Cervicofacial actinomycosis - Predisposing factors: Tooth extraction, jaw fractures, periodontal abscesses, foreign bodies, suppurating tonsillar crypts, immunosuppression

Answer 682

Presence of yellowish sulphur granules in pus. Mx: Prolonged antibiotic therapy, typically amoxicillin for 6 months or longer; surgical drainage may be needed for abscesses

Answer 683

GABA_B agonist. Dose escalation limited by sedation.

Answer 684

Gamma-hydroxybutyrate (GHB)

Answer 685

Acute hepatitis, idiopathic thrombocytopaenic purpura (ITP), transverse myelitis, arthritis, Stevens-Johnson syndrome

Answer 686

Macrolide antibiotics, e.g., clarithromycin; empirical regimens may combine co-amoxiclav with clarithromycin

Answer 687

Corneal microdeposits (night-time visual glare)

Answer 688

1. Fluids + correct electrolye imbalances (K) 2. Digoxin-specific antibodies ## Footnote Digoxin-specific antibodies offer temporary reversal of toxicity, but ultimately patients require renal excretion of digoxin and, if there is poor urine output and renal impairment, then haemodialysis may be required. Once administered, it is not possible to reliably measure circulating digoxin concentrations. Serum sickness is an uncommon but recognised and potentially life-threatening reaction.

Answer 689

The internal capsule receives its blood supply from the lenticulostriate vessels

Answer 690

The lentiform nucleus consists of an outer putamen and an inner globus pallidus. The anterior limb lies between the head of the caudate nucleus and the lentiform nucleus.

Answer 691

Amphetamine use may be associated with mydriasis, hypertension, tachycardia, skin pallor, hyperexcitability and, in the initial stages, agitation and increased talkativeness and euphoria. Hypokalaemia is seen as a result of sympathetic stimulation. Severe toxicity may be associated with hyperpyrexia, rhabdomyolysis, acute kidney disease and acute liver failure. ## Footnote Benzodiazepines may not effectively mitigate hypertension in certain patients with amphetamine-related toxicity. If hypertension persists, the mixed alpha/beta-blocker labetalol has been shown to be safe and effective.

Answer 692

Diuretic-induced volume depletion ## Footnote Relative volume depletion is a feature of cirrhosis, due to hypoalbuminaemia driving low colloid osmotic pressure. This drives increased aldosterone, which is not adequately metabolised by an impaired liver. Furosemide use in the post-operative period further exacerbates alkalosis driven by hyperaldosteronism and could be responsible for the presentation here.

Answer 693

Patient should be given desmopressin periprocedure

Answer 694

Decreased aortic compliance ## Footnote Decreased aortic compliance with increasing age means that the aorta is less able to absorb the pulse wave that comes from left ventricular contraction, increasing pulse pressure. Peripheral vascular resistance leads to an overall increase in blood pressure rather than having a particularly strong impact on the difference between systolic and diastolic BP (pulse pressure).

Answer 695

Hyperuricaemia ## Footnote Hypertrichosis and gum hypertrophy are also widely reported in association with ciclosporin treatment. Ciclosporin is metabolised by CYP3А4, therefore patients taking it, and their physicians, need to be careful with respect to possible drug interactions, such as with statins or macrolide antibiotics.

Answer 696

* hyperosmolar feed * bacterial contamination * low feed temperature * reduced intestinal absorptive capacity * too rapid or irregular administration * lactose intolerance.

Answer 697

Inadequate fluid replacement

Answer 698

Basal layer of the epidermis ## Footnote The melanin system is composed of a melanocyte that supplies melanin to a group of keratinocytes to form a so-called 'melanin unit'. Melanocytes are dendritic cells and have no desmosomes, (intercellular bridges); they have a small dark nucleus and clear cytoplasm.

Answer 699

PTU blocks conversion of T4 to T3 in peripheral tissues (does not inactivate existing T4 and T3 stores in circulating blood) ## Footnote Propylthiouracil (PTU) and carbimazole are both derivatives of thiourea with similar chemical structure, mechanisms of action and adverse effects. Both are capable of inhibiting organification of iodine at the thyroid gland. Neither drug affects iodine trapping and neither drug inhibits the release of preformed thyroid hormone. A key distinction is that PTU also blocks conversion of Tato T3 in peripheral tissues (does not inactivate existing T4 and T3 stores in circulating blood and the thyroid and does not interfere with replacement thyroid hormones). This may give PTU a modest therapeutic advantage because it reduces the proportion of active thyroid hormone as well as total T4. Both PTU and carbimazole are excreted in very small quantities in breast milk, so breast feeding is not advised with either. Thiourea derivatives have several side-effects, including a maculopapular rash, hepatocellular damage and vasculitis. The most serious side-effect of both agents is agranulocytosis, although it is more common to see a fall in, rather than total absence of, white cells.

Answer 700

Cardiomyopathy ## Footnote Female carriers of Duchenne muscular dystrophy (DMD) may develop symptomatic cardiomyopathy, with a 10-20% lifetime risk of developing the disorder. Cohort studies suggest that 80% of women and girls above the age of 16 years have at least early changes consistent with myocardial involvement, although the majority do not have symptoms of cardiac dysfunction. In boys, DMD (an X-linked condition) is diagnosed between the ages of 3 and 6 years with difficulty walking and calf pseudohypertrophy. Death occurs due to cardiomyopathy and/or respiratory failure by age 30. CK is always grossly elevated in conjunction with clinical disease.

Answer 701

Upper airway obstruction ## Footnote Anaplastic carcinoma is the rarest of all thyroid tumours (<1%). Cervical lymph node metastases are present in 90% at diagnosis, lung metastases in 50% and tracheal invasion in 25%. Anaplastic carcinoma has a very poor prognosis with a median survival of 4-5 months. The most common sequela is upper airway obstruction. Surgery has a limited role in relieving obstructive symptoms; external beam radiotherapy is useful in palliation. The role of chemotherapy (usually doxorubicin combined with other drugs) is unclear. Many patients will require a tracheostomy to manage airway obstruction. Brain and liver metastases may occur but are not common. Bone, lung and cervical lymph node metastases are common. Hypercalcaemia is not a feature of anaplastic thyroid cancer unless secondary to bone metastases. In medullary thyroid cancer, calcium metabolism can be disordered owing to elevated levels of calcitonin secreted by the tumour.

Answer 702

Adjuvant chemotherapy is the standard therapy for patients with stage || and Ill non-small cell lung cancer (NSCLC) after radical surgery, with improvement in 5-year survival of approximately 5%.

Answer 703

Common features include hot, dry skin, hypertension, tachycardia, dilated pupils, urinary retention, constipation and delirium. ## Footnote Drugs with anticholinergic properties include tricyclic antidepressants, antipsychotics and antihistamines. In most cases, withdrawal of the offending drug is all that is required, along with supportive care.

Answer 704

Desferrioxamine ## Footnote Reasons cannot tolerate: anaemia, severe cardiac disease

Answer 705

Meptazinol is a partial mu opioid receptor agonist; as such, it is an effective opioid analgesic associated with a lower risk of constipation versus other agents such as codeine or morphine. ## Footnote A stimulant laxative, such as senna, is the initial preferred intervention for preventing opiate-induced constipation and is recommended by National Institute for Health and Care Excellence (NICE) palliative care guidelines. Lactulose or macrogol can be added to senna in the event that the stimulant laxative alone is inadequate in constipation prevention.

Answer 706

Decreased androgen production ## Footnote Buserelin is a gonadotrophin releasing hormone agonist that exerts its actions at the level of the pituitary gland. Initially treatment causes increased gonadotrophin release; however, after a few weeks of continued therapy, gonadotrophin production is inhibited, and testosterone levels fall. The initial increase in testosterone levels may be accompanied by a 'flare' in disease symptoms in some patients.

Answer 707

Simple OE - infection of the external auditory canal Malignant OE - swelling and facial nerve involvement (almost all cases are in diabetic patients) Organism = Pseudomonas aeruginosa

Answer 708

Heparin inhibits aldosterone secretion by the adrenal cortex, leading to impaired renal potassium excretion, particularly in patients with diabetes or those who are acidotic.

Answer 709

Bicarbonate and haemoglobin ## Footnote Deoxyhaemoglobin is a much more effective buffer than oxyhemoglobin which accounts for some proportion of the Haldane effect (the effect of oxygen on haemoglobin, reducing its ability to transport carbon dioxide).

Answer 710

Calcium supplementation ## Footnote In enteric hyperoxaluria (the diagnosis here), supplemental calcium binds to any free intestinal oxalate, thereby reducing its absorption. Calcium supplementation may provide an additional benefit with respect to bone health, given that calcium absorption is often disordered in patients with small bowel pathology. Patients should also alter their diet, if possible, to reduce the amount of oxalate they consume (examples of very highoxalate foods include rhubarb and beetroot) and increase their fluid intake. Potassium citrate may have a role in correcting metabolic acidosis, if present.

Answer 711

Generation of reactive oxygen species ## Footnote The phenomenon of nitrate tolerance was first described 30+ years ago, but the pharmacological basis has only been elucidated more recently. It is thought that chronic nitrate therapy may increase vascular oxidative stress, which results in enhanced degradation of nitric oxide (NO) and reduced bioavailability. Resulting reactive oxygen and reactive nitrate species then lead to inhibition of the bioactivation of exogenously administered nitrate.

Answer 712

120 mmol ## Footnote 120 mmol daily is an appropriate potassium replacement for an adult with active gastrointestinal losses from diarrhoea. Standard adult potassium requirements are approximately 60-90 mmol/day to maintain normal balance, but these rise significantly in the presence of ongoing losses such as diarrhoea or vomiting. Patients with Crohn's disease and recent bowel surgery are at particular risk of depletion due to both increased loss and impaired absorption. In this clinical scenario, 120 mmol/day provides a safe yet effective replacement to both correct the existing deficit and meet increased daily needs, reducing the risk of complications such as arrhythmias or muscle weakness.

Answer 713

Domperidone ## Footnote This patient has diabetic gastroparesis, a recognised microvascular complication of long-standing type 1 diabetes. It is characterised by delayed gastric emptying leading to unpredictable vomiting and regurgitation of undigested food. Domperidone is a prokinetic dopamine antagonist that acts peripherally without crossing the blood-brain barrier, so it avoids central neurological side-effects. NICE guidance supports domperidone, metoclopramide and erythromycin as treatment options, but domperidone is generally preferred first because of its peripheral action and favourable tolerability profile, provided QT prolongation risk is assessed.

Answer 714

Plasmodium ovale ## Footnote This gentleman is likely to have malaria due to Plasmodium ovale, because all stages are visible in the peripheral blood. In P. falciparum malaria, only trophozoite-ring forms and gametocytes are usually seen. It is also unlikely to be P. vivax as West Africans lack the Duffy red cell antigen that is the receptor for P. vivax. The treatment of choice for acute non-falciparum malaria is either with artemisinin combination therapy (ACT) or chloroquine. Further treatment with primaquine is needed to eradicate the liver hypnozoites - all individuals should be screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency, as primaquine may cause haemolysis in those without the enzyme.

Answer 715

Systemic mastocytosis is associated with increased histamine production, and consequently increased gastric acid secretion.

Answer 716

Type Il or Ill cryoglobulinaemia ## Footnote Both types are associated with the presence of IgM rheumatoid factor. Where there is evidence of end-organ damage, as there is here, corticosteroids in conjunction with a secondline agent such as cyclophosphamide or azathioprine are the mainstay of therapy. Non-steroidal antiinflammatory drugs may be useful in the management of arthralgia.

Answer 717

Weber syndrome ## Footnote Infarction in the midbrain due to occlusion of the paramedian branches of the posterior cerebral artery (PCA). Ipsilateral oculomotor nerve (CN III) palsy + Contralateral hemiparesis (UMN signs) ✅ Memory hook: Think “Weber = Weakness + Eye (III)” Weakness (contralateral body) Eye palsy (ipsilateral CN III)

Answer 718

Anaemia occurs only in lead poisoning due to inhibition of ferrochelatase (the activity of this enzyme is normal in acute intermittent porphyria), a decrease in red cell lifespan, and inhibition of pyrimidine 5'nucleotidase leading to the accumulation of pyrimidine nucleotides in red cells, which in turn reduces the stability of the cell membrane (and is seen on a blood film as basophilic stippling).

Answer 719

non-nucleoside reverse-transcriptase inhibitor e.g. nevirapine

Answer 720

Blurring of the upper and/or lower vertebral rims at the sacroiliac junction ## Footnote The earliest radiological appearances in the spine are blurring of the upper and/or lower vertebral rims at the sacroiliac junction (best seen on a lateral X-ray). This is caused by an enthesitis at the insertion of the intervertebral ligaments. Persistent enthesitis causes bony spurs (syndesmophytes). Fusion and sclerosis of the sacroiliac joints and calcification of intervertebral ligaments occur at a later stage.

Answer 721

Oestrogen ## Footnote The growth spurt at puberty is brought about by the secretion of androgens in the male and oestrogens in the female. However, it is ostrogens that ultimately terminate growth by causing the epiphyses in the long bones to fuse. Ostrogens rather than androgens are therefore responsible for skeletal maturation, epiphyseal fusion and cessation of growth in males and females.

Answer 722

Inducing apoptosis ## Footnote P1 receptors are G-protein coupled membrane receptors preferentially bound by adenosine. There are a number of subtypes and thus a range of physiological effects. However, as a class the receptor is predominantly involved in mast cell function and eosinophil apoptosis - essentially functioning as a brake on an activated immune system

Answer 723

Donepezil is a cholinesterase inhibitor, and as such potentiates the actions of cholinergic neurones. Adverse effects include nausea, vomiting and diarrhoea; cardiac side-effects include bradycardia and, rarely, AV block. Less common effects include urinary incontinence and hepatitis.

Answer 724

Type II hypersensitivity reaction ## Footnote Idiopathic Thrombocytopenic Purpura (ITP) is an example of a Type II hypersensitivity reaction, also known as cytotoxic hypersensitivity. In this type of reaction, the immune system produces IgG antibodies that bind to self-antigens on cell surfaces, in the case of ITP, these are platelet antigens. This leads to the destruction of the cells by phagocytosis or complement activation which results in thrombocytopenia and purpura.

Answer 725

Stroke volume / end diastolic LV volume. ## Footnote Left ventricular ejection fraction (LVEF) is a key measure of cardiac function that represents the percentage of blood ejected from the left ventricle during systole relative to the total volume of blood in the ventricle at the end of diastole. The formula for calculating LVEF is: LVEF = (Stroke Volume / End Diastolic Volume) × 100% Where stroke volume is the difference between end diastolic volume and end systolic volume.

Answer 726

Non-REM stage 1 (N1) sleep is the lightest sleep which is associated with hypnagogic jerks

Answer 727

the probability of obtaining a result by chance at least as extreme as the one that was actually observed, assuming that the null hypothesis is true ## Footnote Firstly we’re assuming the null hypothesis is true - so you’re presuming there’s no difference between the two groups. Now when you get a result that does show a difference, the p value now is essentially the probability of getting this result again or a result that’s as extreme as in showing a difference to the same effect between the two groups

Answer 728

IL-4, IL-5, IL-6, IL-10, IL-13 ## Footnote Th1, IL2, IL3 (1,2,3) +gamma Th2 all the rest

Answer 729

Alkaptonuria ## Footnote Alkaptonuria is an autosomal recessive disorder that is a result of a deficiency of homogentisic acid dioxygenase leading to elevated levels of homogentisic acid (HGA). HGA then polymerises and forms a pigment that is deposited in connective tissue throughout the body (ochronosis). Clinically features include brown/bluish pigment of the ear cartilage or sclera, arthropathy, renal stones, cardiac valve involvement and coronary calcification.

Answer 730

IgM ## Footnote IgM antibodies are primarily responsible for haemolytic transfusion reactions. They are the first immunoglobulin to be produced in response to an antigen and are especially effective at agglutination, which makes them crucial in the immune response against blood group antigens. Haemolytic transfusion reactions occur when donor blood is not compatible with the recipient's blood type. This triggers an immune response where IgM antibodies bind to the foreign antigens on the transfused red blood cells, leading to their destruction (haemolysis).

Answer 731

Reduces secretion ## Footnote Beta-blockers work by blocking the effects of the hormone adrenaline, also known as epinephrine. They do this by binding to beta receptors on cells in the heart and blood vessels, which are the sites where adrenaline acts. This prevents adrenaline from causing an increase in heart rate, blood pressure, and renin secretion. Therefore, beta-blockers reduce the secretion of renin.

Answer 732

Kimmelstiel-Wilson lesions, nodular glomerulosclerosis

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