Passmed MRCP Flashcards
The most common causes of a sudden painless loss of vision are as follows:
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
Central retinal vein occlusion
incidence increases with age, more common than arterial occlusion
causes: glaucoma, polycythaemia, hypertension
severe retinal haemorrhages are usually seen on fundoscopy
Central retinal artery occlusion
due to thromboembolism (from atherosclerosis) or arteritis (e.g. temporal arteritis)
features include afferent pupillary defect, ‘cherry red’ spot on a pale retina
Central retinal vein occlusion
sudden painless loss of vision, severe retinal haemorrhages on fundoscopy
emporal lobe seizure
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
Frontal lobe (motor) seizure
Head/leg movements, posturing, post-ictal weakness, Jacksonian march
Parietal lobe (sensory) seizure
Paraesthesia
Hashimoto’s thyroiditis is associated with the development of
MALT lymphoma
Hashimoto’s thyroiditis features
Features
features of hypothyroidism
goitre: firm, non-tender
anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies
Hashimoto’s thyroiditis Associations
Associations
other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo
Hashimoto’s thyroiditis is associated with the development of MALT lymphoma
Porphyria cutanea tardaFeatures
Features
classically presents with photosensitive rash with blistering and skin fragility on the face and dorsal aspect of hands (most common feature)
hypertrichosis
hyperpigmentation
Porphyria cutanea tarda I + M
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
Cinacalcet
calcimimetic - a drug that ‘mimics’ the action of calcium on tissue by allosteric activation of the calcium-sensing receptor
Primary hyperparathyroidism
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
Gastroparesis
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
Oesophageal cancer Adenocarcinoma
Lower third - near the gastroesophageal junction
GORD
Barrett’s oesophagus
smoking
obesity
Oesophageal cancer
Squamous cell cancer
Upper two-thirds of the oesophagus
Myeloma CRABBI
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
Hereditary angioedema screening between tests
C4
Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide
increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss
Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)
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
Hypokalaemia and hypertension
Hypokalaemia with hypertension
Cushing’s syndrome
Conn’s syndrome (primary hyperaldosteronism)
Liddle’s syndrome
11-beta hydroxylase deficiency*
IgA nephropathy Associated conditions
Associated conditions
alcoholic cirrhosis
coeliac disease/dermatitis herpetiformis
Henoch-Schonlein purpura
Pathophysiology
IgA nephropathy
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
Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis
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
Management IgA nephropathy
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
Phenytoin MoA
Mechanism of action
binds to sodium channels increasing their refractory period
Phenytoin AE
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
Monitoring
Phenytoin
adjustment of phenytoin dose
suspected toxicity
detection of non-adherence to the prescribed medication
Desmopressiin
induces release of von Willebrand’s factor from endothelial cells
Von Willebrand’s disease
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
Selegiline
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.
levodopa
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
Dopamine receptor agonists
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
Amantadine
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
COMT (Catechol-O-Methyl Transferase) inhibitors
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
Antimuscarinics
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)
Patients with type I diabetes and a BMI > 25
considered for metformin in addition to insulin
Restless leg syndrome
management includes dopamine agonists such as ropinirole
Indications for corticosteroid treatment for sarcoidosis are:
parenchymal lung disease, uveitis, hypercalcaemia and neurological or cardiac involvement
Avascular necrosis (AVN) causes
Causes
long-term steroid use
chemotherapy
alcohol excess
trauma
gold standard test for achalasia i
oesophageal manometry
Aortic stenosis: clinical features of symptomatic disease
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
Features of severe aortic stenosis
narrow pulse pressure
slow rising pulse
delayed ESM
soft/absent S2
S4
thrill
duration of murmur
left ventricular hypertrophy or failure
Causes of aortic stenosis
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
aortic stenosis Management
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
Furosemide Moa
inhibits the Na-K-Cl cotransporter in the thick ascending limb of the loop of Henle
Indapamide moa
inhibiting the sodium-chloride symporter (NCC) in the distal convoluted tubule
Eplerenone moa
acts as a selective aldosterone receptor antagonist blocking aldosterone-mediated sodium reabsorption and potassium secretion at the level of collecting ducts.
Amiloride moa
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.
Rapid depolarisation
Rapid sodium influx
These channels automatically deactivate after a few ms
Early repolarisation
Efflux of potassium
Plateau
Slow influx of calcium
Final repolarisation
Efflux of potassium
Restoration of ionic concentrations
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
Tricyclic overdose ECG changes
ECG changes include:
sinus tachycardia
widening of QRS
prolongation of QT interval
Pulmonary arterial hypertension (PAH) may be defined as
resting mean pulmonary artery pressure of >= 20 mmHg. Endothelin thought to play a key role in pathogenesis of PAH.
to decide treatment in Pulmonary arterial hypertension
acute vasodilator testing i
PAH If there is a positive response to acute vasodilator testing
oral calcium channel blockers
PAH f there is a negative response to acute vasodilator testing (the vast majority of patients
prostacyclin analogues: treprostinil, iloprost
endothelin receptor antagonists
non-selective: bosentan
selective antagonist of endothelin receptor A: ambrisentan
phosphodiesterase inhibitors: sildenafil
Insulin abuse
raised insulin with low c-peptide level
sulfonylurea-induced hypoglycemia
insulin and C-peptide Rise
cell surface proteins associated with particular cell types: Haematopoietic stem cells
CD34
Helper T cell cell surface proteins
CD4, TCR, CD3, CD28
Cytotoxic T cell cell surface proteins
CD8, TCR, CD3, CD28
Regulatory T cell cell surface proteins
CD4, CD25, TCR, CD3, CD28
B cell cell surface proteins
CD19, CD20, CD40,
MHC II, cell surface proteins
B7
Macrophage cell surface proteins
CD14, CD40, Natural killer cell
most common cause of neutropenic sepsis
Coagulase-negative, Gram-positive bacteria such as Staphylococcus epidermidis
