Passmed MRCP

Question 1

The most common causes of a sudden painless loss of vision are as follows:

Answer 1

The most common causes of a sudden painless loss of vision are as follows:
ischaemic/vascular (e.g. thrombosis, embolism, temporal arteritis etc). This includes recognised syndromes e.g. occlusion of central retinal vein and occlusion of central retinal artery
vitreous haemorrhage
retinal detachment
retinal migraine

Question 2

Central retinal vein occlusion

Answer 2

incidence increases with age, more common than arterial occlusion
causes: glaucoma, polycythaemia, hypertension
severe retinal haemorrhages are usually seen on fundoscopy

Question 3

Central retinal artery occlusion

Answer 3

due to thromboembolism (from atherosclerosis) or arteritis (e.g. temporal arteritis)
features include afferent pupillary defect, ‘cherry red’ spot on a pale retina

Question 4

Central retinal vein occlusion

Answer 4

sudden painless loss of vision, severe retinal haemorrhages on fundoscopy

Question 5

emporal lobe seizure

Answer 5

May occur with or without impairment of consciousness or awareness

An aura occurs in most patients
typically a rising epigastric sensation
also psychic or experiential phenomena, such as dejà vu, jamais vu
less commonly hallucinations (auditory/gustatory/olfactory)

Seizures typically last around one minute
automatisms (e.g. lip smacking/grabbing/plucking) are common

Question 6

Frontal lobe (motor) seizure

Answer 6

Head/leg movements, posturing, post-ictal weakness, Jacksonian march

Question 7

Parietal lobe (sensory) seizure

Answer 7

Paraesthesia

Question 8

Hashimoto’s thyroiditis is associated with the development of

Answer 8

MALT lymphoma

Question 9

Hashimoto’s thyroiditis features

Answer 9

Features
features of hypothyroidism
goitre: firm, non-tender
anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies

Question 10

Hashimoto’s thyroiditis Associations

Answer 10

Associations
other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo
Hashimoto’s thyroiditis is associated with the development of MALT lymphoma

Question 11

Porphyria cutanea tardaFeatures

Answer 11

Features
classically presents with photosensitive rash with blistering and skin fragility on the face and dorsal aspect of hands (most common feature)
hypertrichosis
hyperpigmentation

Question 12

Porphyria cutanea tarda I + M

Answer 12

nvestigations
urine: elevated uroporphyrinogen and pink fluorescence of urine under Wood’s lamp
serum iron ferritin level is used to guide therapy

Management
chloroquine
venesection
preferred if iron ferritin is above 600 ng/ml

Question 13

Cinacalcet

Answer 13

calcimimetic - a drug that ‘mimics’ the action of calcium on tissue by allosteric activation of the calcium-sensing receptor

Question 14

Primary hyperparathyroidism

Answer 14

is caused by excess secretion of PTH resulting in hypercalcaemia. It is the most common cause of hypercalcaemia in outpatients and is often diagnosed following an incidental finding of an elevated serum calcium concentration. In 85% of cases a parathyroid adenoma is responsible.

Causes of primary hyperparathyroidism
85%: solitary adenoma
10%: hyperplasia
4%: multiple adenoma
1%: carcinoma

Question 15

Gastroparesis

Answer 15

occurs secondary to autonomic neuropathy
symptoms include erratic blood glucose control, bloating and vomiting
management options include metoclopramide, domperidone or erythromycin (prokinetic agents)

Chronic diarrhoea
often occurs at night

Gastro-oesophageal reflux disease
caused by decreased lower esophageal sphincter (LES) pressure

Question 16

Oesophageal cancer Adenocarcinoma

Answer 16

Lower third - near the gastroesophageal junction
GORD
Barrett’s oesophagus
smoking
obesity

Question 17

Oesophageal cancer
Squamous cell cancer

Answer 17

Upper two-thirds of the oesophagus

Question 18

Myeloma CRABBI

Answer 18

Use the mnemonic CRABBI:
Calcium
hypercalcaemia
primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells
much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels
this leads to constipation, nausea, anorexia and confusion
Renal
monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
this causes renal damage which presents as dehydration and increasing thirst
other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
Anaemia
bone marrow crowding suppresses erythropoiesis leading to anaemia
this causes fatigue and pallor
Bleeding
bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
Bones
bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
this may present as pain (especially in the back) and increases the risk of pathological fractures
Infection
a reduction in the production of normal immunoglobulins results in increased susceptibility to infection

Question 19

Hereditary angioedema screening between tests

Answer 19

C4

Question 20

Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide

Answer 20

increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss

Question 21

Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)

Answer 21

ey points
dipeptidyl peptidase-4, DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown
oral preparation
trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia
do not cause weight gain

NICE guidelines on DPP-4 inhibitors
NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione

Question 22

Hypokalaemia and hypertension

Answer 22

Hypokalaemia with hypertension
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
Liddle’s syndrome
11-beta hydroxylase deficiency*

Question 23

IgA nephropathy Associated conditions

Answer 23

Associated conditions
alcoholic cirrhosis
coeliac disease/dermatitis herpetiformis
Henoch-Schonlein purpura

Question 24

Pathophysiology
IgA nephropathy

Answer 24

Pathophysiology
thought to be caused by mesangial deposition of IgA immune complexes
there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)
histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3

Question 25

Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis

Answer 25

post-streptococcal glomerulonephritis is associated with low complement levels main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria can occur) there is typically an interval between URTI and the onset of renal problems in post-streptococcal glomerulonephritis

Question 26

Management IgA nephropathy

Answer 26

isolated hematuria, no or minimal proteinuria (less than 500 to 1000 mg/day), and a normal glomerular filtration rate (GFR) no treatment needed, other than follow-up to check renal function persistent proteinuria (above 500 to 1000 mg/day), a normal or only slightly reduced GFR initial treatment is with ACE inhibitors if there is active disease (e.g. falling GFR) or failure to respond to ACE inhibitors immunosuppression with corticosteroids

Question 27

Phenytoin MoA

Answer 27

Mechanism of action binds to sodium channels increasing their refractory period

Question 28

Phenytoin AE

Answer 28

Phenytoin is associated with a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic. Phenytoin is also an inducer of the P450 system. Acute initially: dizziness, diplopia, nystagmus, slurred speech, ataxia later: confusion, seizures Chronic common: gingival hyperplasia (secondary to increased expression of platelet derived growth factor, PDGF), hirsutism, coarsening of facial features, drowsiness megaloblastic anaemia (secondary to altered folate metabolism) peripheral neuropathy enhanced vitamin D metabolism causing osteomalacia lymphadenopathy dyskinesia

Question 29

Monitoring Phenytoin

Answer 29

adjustment of phenytoin dose suspected toxicity detection of non-adherence to the prescribed medication

Question 30

Desmopressiin

Answer 30

induces release of von Willebrand's factor from endothelial cells

Question 31

Von Willebrand's disease

Answer 31

Von Willebrand's disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare

Question 32

Selegiline

Answer 32

MAO-B inhibitor used mainly in the management of Parkinson's disease (PD) and inhibits the breakdown of dopamine secreted by the dopaminergic neurons. MAO-B inhibitors should be trialled as a potential adjunctive therapy if patients continue to have symptoms despite optimal treatment on levodopa or if they develop dyskinesia. Common side effects of MAO-B inhibitors include fatigue, constipation and a dry mouth.

Question 33

levodopa

Answer 33

nearly always combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) this prevents the peripheral metabolism of levodopa to dopamine outside of the brain and hence can reduce side effects common adverse effects: dry mouth anorexia palpitations postural hypotension psychosis some adverse effects are due to the difficulty in achieving a steady dose of levodopa end-of-dose wearing off: symptoms often worsen towards the end of dosage interval. This results in a decline of motor activity 'on-off' phenomenon: large variations in motor performance, with normal function during the 'on' period, and weakness and restricted mobility during the 'off' period dyskinesias at peak dose: dystonia, chorea and athetosis (involuntary writhing movements) these effects may worsen over time with - clinicians therefore may limit doses until necessary it is important not to acutely stop levodopa, for example, if a patient is admitted to hospital if a patient with Parkinson's disease cannot take levodopa orally, they can be given a dopamine agonist patch as rescue medication to prevent acute dystonia

Question 34

Dopamine receptor agonists

Answer 34

e.g. bromocriptine, ropinirole, cabergoline, apomorphine ergot-derived dopamine receptor agonists (bromocriptine, cabergoline) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patients

Question 36

Amantadine

Answer 36

mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis

Question 37

COMT (Catechol-O-Methyl Transferase) inhibitors

Answer 37

e.g. entacapone, tolcapone COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy used in conjunction with levodopa in patients with established PD

Question 38

Antimuscarinics

Answer 38

block cholinergic receptors now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson's disease help tremor and rigidity e.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)

Question 39

Patients with type I diabetes and a BMI > 25

Answer 39

considered for metformin in addition to insulin

Question 40

Restless leg syndrome

Answer 40

management includes dopamine agonists such as ropinirole

Question 41

Indications for corticosteroid treatment for sarcoidosis are:

Answer 41

parenchymal lung disease, uveitis, hypercalcaemia and neurological or cardiac involvement

Question 42

Avascular necrosis (AVN) causes

Answer 42

Causes long-term steroid use chemotherapy alcohol excess trauma

Question 43

gold standard test for achalasia i

Answer 43

oesophageal manometry

Question 44

Aortic stenosis: clinical features of symptomatic disease

Answer 44

chest pain dyspnoea syncope / presyncope (e.g. exertional dizziness) murmur an ejection systolic murmur (ESM) is classically seen in aortic stenosis classically radiates to the carotids this is decreased following the Valsalva manoeuvre

Question 45

Features of severe aortic stenosis

Answer 45

narrow pulse pressure slow rising pulse delayed ESM soft/absent S2 S4 thrill duration of murmur left ventricular hypertrophy or failure

Question 46

Causes of aortic stenosis

Answer 46

degenerative calcification (most common cause in older patients > 65 years) bicuspid aortic valve (most common cause in younger patients < 65 years) William's syndrome (supravalvular aortic stenosis) post-rheumatic disease subvalvular: HOCM

Question 47

aortic stenosis Management

Answer 47

if asymptomatic then observe the patient is a general rule if symptomatic then valve replacement if asymptomatic but valvular gradient > 40 mmHg and with features such as left ventricular systolic dysfunction then consider surgery options for aortic valve replacement (AVR) include: surgical AVR is the treatment of choice for young, low/medium operative risk patients. Cardiovascular disease may coexist. For this reason, an angiogram is often done prior to surgery so that the procedures can be combined transcatheter AVR (TAVR) is used for patients with a high operative risk balloon valvuloplasty may be used in children with no aortic valve calcification in adults limited to patients with critical aortic stenosis who are not fit for valve replacement

Question 48

Furosemide Moa

Answer 48

inhibits the Na-K-Cl cotransporter in the thick ascending limb of the loop of Henle

Question 49

Indapamide moa

Answer 49

inhibiting the sodium-chloride symporter (NCC) in the distal convoluted tubule

Question 50

Eplerenone moa

Answer 50

acts as a selective aldosterone receptor antagonist blocking aldosterone-mediated sodium reabsorption and potassium secretion at the level of collecting ducts.

Question 51

Amiloride moa

Answer 51

Amiloride works by blocking epithelial sodium channels (ENaC) on the luminal side of principal cells in collecting ducts, resulting in decreased reabsorption of sodium ions and increased excretion of potassium ions.

Question 52

Rapid depolarisation

Answer 52

Rapid sodium influx These channels automatically deactivate after a few ms

Question 53

Early repolarisation

Answer 53

Efflux of potassium

Question 54

Plateau

Answer 54

Slow influx of calcium

Question 55

Final repolarisation

Answer 55

Efflux of potassium

Question 56

Restoration of ionic concentrations

Answer 56

Resting potential is restored by Na+/K+ ATPase There is slow entry of Na+ into the cell decreasing the potential difference until the threshold potential is reached, triggering a new action potential

Question 57

Tricyclic overdose ECG changes

Answer 57

ECG changes include: sinus tachycardia widening of QRS prolongation of QT interval

Question 58

Pulmonary arterial hypertension (PAH) may be defined as

Answer 58

resting mean pulmonary artery pressure of >= 20 mmHg. Endothelin thought to play a key role in pathogenesis of PAH.

Question 59

to decide treatment in Pulmonary arterial hypertension

Answer 59

acute vasodilator testing i

Question 60

PAH If there is a positive response to acute vasodilator testing

Answer 60

oral calcium channel blockers

Question 61

PAH f there is a negative response to acute vasodilator testing (the vast majority of patients

Answer 61

prostacyclin analogues: treprostinil, iloprost endothelin receptor antagonists non-selective: bosentan selective antagonist of endothelin receptor A: ambrisentan phosphodiesterase inhibitors: sildenafil

Question 62

Insulin abuse

Answer 62

raised insulin with low c-peptide level

Question 63

sulfonylurea-induced hypoglycemia

Answer 63

insulin and C-peptide Rise

Question 64

cell surface proteins associated with particular cell types: Haematopoietic stem cells

Answer 64

CD34

Question 65

Helper T cell cell surface proteins

Answer 65

CD4, TCR, CD3, CD28

Question 66

Cytotoxic T cell cell surface proteins

Answer 66

CD8, TCR, CD3, CD28

Question 67

Regulatory T cell cell surface proteins

Answer 67

CD4, CD25, TCR, CD3, CD28

Question 68

B cell cell surface proteins

Answer 68

CD19, CD20, CD40,

Question 69

MHC II, cell surface proteins

Answer 69

B7

Question 70

Macrophage cell surface proteins

Answer 70

CD14, CD40, Natural killer cell

Question 72

most common cause of neutropenic sepsis

Answer 72

Coagulase-negative, Gram-positive bacteria such as Staphylococcus epidermidis