Passmed Round 1 Flashcards
In intravascular haemolysis, free haemoglobin is released which then binds to —— As ———– becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by ———–). Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria
In intravascular haemolysis, free haemoglobin is released which then binds to HAPTOGLOBIN. As HAPTOGLOBIN becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by SCHUMM’S TEST). Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria
Intravascular haemolysis causes?
- Mismatched blood transfusion
- G6PD deficiency*
- Red cell fragmentation: heart valves, TTP, DIC, HUS
- Paroxysmal nocturnal haemoglobinuria
- Cold autoimmune haemolytic anaemia
*strictly speaking there is an element of extravascular haemolysis in G6PD as well, although it is usually classified as a intravascular cause
Extravascular haemolysis causes?
- Haemoglobinopathies: sickle cell, thalassaemia
- Hereditary spherocytosis
- Haemolytic disease of newborn
- Warm autoimmune haemolytic anaemia
Wilson’s disease is an —– genetic —– disorder characterised by excessive copper deposition in the tissues. Metabolic abnormalities include increased ———- and decreased ——–. Wilson’s disease is caused by a defect in ——- located on chromosome ——.
Wilson’s disease is an autosomal recessive disorder characterised by excessive copper deposition in the tissues. Metabolic abnormalities include increased copper absorption from the small intestine and decreased hepatic copper excretion. Wilson’s disease is caused by a defect in the ATP7B gene located on chromosome 13.
Small vessel vasculitides are divided into two brackets.
What are they?
Which vasculitides are in each bracket?
ANCA-associated vasculitides
- granulomatosis with polyangiitis (Wegener’s granulomatosis)
- eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
- microscopic polyangiitis
immune complex small-vessel vasculitis
- Henoch-Schonlein purpura
- Goodpasture’s syndrome (anti-glomerular basement membrane disease)
- cryoglobulinaemic vasculitis
- hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)
What antibodies are associated with SLE?
- 99% are ANA positive
- —-this high sensitivity makes it a useful rule out test, but —–it has low specificity
- 20% are rheumatoid factor positive
- anti-dsDNA: highly specific (> 99%), but less sensitive (70%)
- anti-Smith: highly specific (> 99%), sensitivity (30%)
- also: anti-U1 RNP, SS-A (anti-Ro) and SS-B (anti-La)
What are the causes of upper lung fibrosis?
CHARTS C - Coal worker's pneumoconiosis H - Histiocytosis/ hypersensitivity pneumonitis A - Ankylosing spondylitis R - Radiation T - Tuberculosis S - Silicosis/sarcoidosis
What are the clinical features of limited systemic sclerosis?
Raynaud’s may be first sign
scleroderma affects face and distal limbs predominately
associated with anti-centromere antibodies
a subtype of limited systemic sclerosis is CREST syndrome: Calcinosis, Raynaud’s phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia
What are the adverse effects of hydroxychloroquine?
bull’s eye retinopathy - may result in severe and permanent visual loss
- —recent data suggest that retinopathy caused by hydroxychloroquine is more common than previously thought and the most recent RCOphth guidelines (March 2018) suggest colour retinal photography and spectral domain optical coherence tomography scanning of the macula
- —-baseline ophthalmological examination and annual screening is generally recommened
What do you use to treat UTI in pregnancy?
if the pregnant woman is symptomatic:
-a urine culture should be sent in all cases
should be treated with an antibiotic for
-first-line: nitrofurantoin (should be avoided near term)
second-line: amoxicillin or cefalexin
-trimethoprim is teratogenic in the first trimester and should be avoided during pregnancy
What are the absolute contraindications to lung transplantation in CF patients?
Burkholderia cepacia colonization
—–Specifically, Burkholderia cepacia genomavar III (cenocepacia) has been found to be associated with a survival rate that is unacceptably low to justify transplantation.
Other absolute contraindications include systemic sepsis and failure to identify an appropriate antibiotic regimen for treatment.
What are the symptoms of the following paraneoplastic antibodies?
Anti -Ri
Anti GAD
Anti-Hu
Anti Yo
Anti-Ri (Rieally blurry vision)
Anti GAD GAAAAD he’s stiff (stiff man syndrome)
Anti-Hu who kicked my chair (pain) and then fell over (ataxia)
Anti yo- Yo lady give me back my danish (cerebellar syndrome, lady for breast + ovarian)
What does a non-pulsatile JVP indicate?
SVC obstruction
Describe the parts of the JVP
a wave - atrial contraction
- increased if atrial pressure (e.g. tricuspid stenosis/ pulm stenosis, pulm hypertension
- Absent in AF
C wave - closure of tricuspid (usually not seen)
x descent - fall in atrial pressure during ventricular systole
V wave - due to passive filling of blood into the atrium against a closed tricuspid valve
-Giant V waves in tricuspid regurg
y descent - opening of tricuspid valve
What is the management of a primary pneumothorax?
if the rim of air is < 2cm and the patient is not short of breath then discharge should be considered
otherwise, aspiration should be attempted
if this fails (defined as > 2 cm or still short of breath) then a chest drain should be inserted
patients should be advised to avoid smoking to reduce the risk of further episodes - the lifetime risk of developing a pneumothorax in healthy smoking men is around 10% compared with around 0.1% in non-smoking men
What is the management of a secondary pneumothorax?
if the patient is > 50 years old and the rim of air is > 2cm and/or the patient is short of breath then a chest drain should be inserted.
otherwise aspiration should be attempted if the rim of air is between 1-2cm. If aspiration fails (i.e. pneumothorax is still greater then 1cm) a chest drain should be inserted.
All patients should be admitted for at least 24 hours
if the pneumothorax is less the 1cm then the BTS guidelines suggest giving oxygen and admitting for 24 hours
regarding scuba diving, the BTS guidelines state: ‘Diving should be permanently avoided unless the patient has undergone bilateral surgical pleurectomy and has normal lung function and chest CT scan postoperatively.’
What are the complications of measles?
otitis media: the most common complication
pneumonia: the most common cause of death
encephalitis: typically occurs 1-2 weeks following the onset of the illness)
subacute sclerosing panencephalitis: very rare, may present 5-10 years following the illness
febrile convulsions
keratoconjunctivitis, corneal ulceration
diarrhoea
increased incidence of appendicitis
myocarditis
Left anterior fascicular block causes what on the ECG?
Left axis deviation
Right anterior fascicular block causes what on the ECG?
Right axis deviation
Right bundle branch block influences the cardiac axis in what way?
No change because left ventricle overrides
What does bifascicular block on ECG show?
RBBB and left axis deviation
What rate is the ventricular escape rhythm?
Around 30 bpm
What rate does the heart have to be to diagnose ventricular tachycardia?
> 120 bpm
What are northern, southern and western blots used for?
SNOW DROP
South - DNA
NOrth - RNA
West - Protein
What are the good prognostic factors in ALL?
French-American-British (FAB) L1 type common ALL pre-B phenotype low initial WBC del(9p) Hyperploidy Trisomy 4, 10 and 17 t(12;21), t(1;19)
What are the poor prognostic factors in ALL?
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 Hypoploidy
What are the glucocorticoid side effects of corticosteroids?
endocrine: impaired glucose regulation, increased appetite/weight gain, hirsutism, hyperlipidaemia
Cushing’s syndrome: moon face, buffalo hump, striae
musculoskeletal: osteoporosis, proximal myopathy,
avascular necrosis of the femoral head
immunosuppression: increased susceptibility to severe infection, reactivation of tuberculosis
psychiatric: insomnia, mania, depression, psychosis
gastrointestinal: peptic ulceration, acute pancreatitis
ophthalmic: glaucoma, cataracts
suppression of growth in children
intracranial hypertension
neutrophilia
Name the Primary Immunodeficiencies categorised as neutrophil disorders
Neutrophil Disorders
- Chronic granulomatous disease
- Chediak-Higashi syndrome
- Leukocyte adhesion deficiency
What drugs cause Steven Johnson Syndrome?
allopurinol carbamazepine lamotrigine nevirapine the "oxicam" class of anti-inflammatory drugs (including meloxicam and piroxicam) phenobarbital phenytoin sulfamethocazole and other sulfa antibiotics sertraline sulfasalazine
What drugs cause pancreatitis?
Thiazides
Azathioprine
Corticosteroids
Sodium valproate
What conditions are HLA-DR3?
dermatitis herpetiformis
Sjogren’s syndrome
primary biliary cirrhosis
What are the signs of hyposplenism on blood film?
Target cells Howell-Jolly bodies Pappenheimer bodies Siderotic granules Acanthocytes
Give examples of mitochondrial disease
Leber’s optic atrophy
MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
MERRF syndrome: myoclonus epilepsy with ragged-red fibres
Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
sensorineural hearing loss
What are the levels of evidence of medical studies?
Ia - evidence from meta-analysis of randomised controlled trials
Ib - evidence from at least one randomised controlled trial
IIa - evidence from at least one well designed controlled trial which is not randomised
IIb - evidence from at least one well designed experimental trial
III - evidence from case, correlation and comparative studies
IV - evidence from a panel of experts
What are the adverse effects of ciclosporin?
nephrotoxicity hepatotoxicity fluid retention hypertension hyperkalaemia hypertrichosis gingival hyperplasia tremor impaired glucose tolerance hyperlipidaemia increased susceptibility to severe infection
What are the risk factors for endometrial cancer?
obesity nulliparity early menarche late menopause unopposed oestrogen. The addition of a progestogen to oestrogen reduces this risk (e.g. In HRT). The BNF states that the additional risk is eliminated if a progestogen is given continuously diabetes mellitus tamoxifen polycystic ovarian syndrome hereditary non-polyposis colorectal carcinoma
What are the clinical features of Von Hippel Lindau syndrome?
cerebellar haemangiomas: these can cause subarachnoid haemorrhages
retinal haemangiomas: vitreous haemorrhage
renal cysts (premalignant)
phaeochromocytoma
extra-renal cysts: epididymal, pancreatic, hepatic
endolymphatic sac tumours
clear-cell renal cell carcinoma
What are the clinical features of Turner Syndrome?
- Short stature
- Shield chest, widely spaced nipples
- Webbed neck
- Bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
- Primary amenorrhoea
- Cystic hygroma (often diagnosed prenatally)
- High-arched palate
- Short fourth metacarpal
- Multiple pigmented naevi
- Lymphoedema in neonates (especially feet)
- Gonadotrophin levels will be elevated
- Hypothyroidism is much more common in Turner’s
- Horseshoe kidney: the most common renal abnormality in Turner’s syndrome
Name the live attenuated vaccines
You Musn’t Prescribe BCG Incase They RIP Stat= Yellow fever, MMR, Polio(oral), BCG, Influenza(intranasal), Typhoid, Rotavirus(oral), Shingles
Yellow fever MMR Polio (oral) BCG Influenza (intranasal) Typhoid Rotavirus (oral) Shingles
Name the inactivated preparation vaccines
rabies
hepatitis A
influenza (intramuscular)
Name the toxoid vaccines
tetanus
diphtheria
pertussis
Name the subunit/ conjugate vaccines
pneumococcus (conjugate) haemophilus (conjugate) meningococcus (conjugate) hepatitis B human papillomavirus
What are the causes of a prolonged PR interval?
idiopathic ischaemic heart disease digoxin toxicity hypokalaemia* rheumatic fever aortic root pathology e.g. abscess secondary to endocarditis Lyme disease sarcoidosis myotonic dystrophy
What are the cyanotic and acyanotic congenital heart conditions?
Cyanotic
- transposition of the great arteries
- tricuspid atresia
- tetralogy of Fallot
Acyanotic
- coarctation of the aorta
- aortic valve stenosis
- ventricular septal defect
- atrial septal defect
What drugs cause ankle swelling?
Amlodipine
Diltiazem
What are the adverse effects of carbamazepine?
P450 enzyme inducer dizziness and ataxia drowsiness headache visual disturbances (especially diplopia) Steven-Johnson syndrome leucopenia and agranulocytosis hyponatraemia secondary to syndrome of inappropriate ADH secretion
What drugs cause headache?
Amlodipine Nicorandil ISMN Carbamazepine Sulphasalazine Ivabradine
What drugs cause hepatotoxicity?
Immunosuppression: Methotrexate, Ciclosporin
TB: Rifampicin, Isoniazid, Pyrazinamide
Antiepileptics: Phenytoin, Sodium Valproate
Diabetic: Pioglitazone, Sulphonurea
Amiodarone
What drugs cause myelofibrosis/ agranulocytosis?
Hydroxurea Cyclophosphamide Flurouracil (5-FU) Irinotecan Methotrexate
What drugs undergo first pass metabolism?
Aspirin Isosorbide dinitrate Glyceryl trinitrate Lignocaine Propranolol Verapamil Isoprenaline Testosterone Hydrocortisone
What drugs exhibit zero order kinetics?
Phenytoin
Salicylates
Heparin
Ethanol
What drugs are affected by acetylator status?
Isoniazid Procainamide Hydralazine Dapsone Sulphasalazine
What drugs cause peripheral neuropathy?
Amiodarone Phenytoin Metronidazole Nitrofurantoin Isoniazid
What drugs cause ataxia
Phenytoin
Carbamazepine
Sodium valproate
Amantadine
What are the features of parietal lobe lesions?
Sensory inattention
Apraxias
Astereognosis (tactile agnostic)
Inferior homonymous quadrantanopia
Gerstmanns syndrome
- lesion of the dominant parietal
- alexia, acalculia, finger agnosia, left right disorientation
What are the features of occipital lobe lesions?
Homonymous hemianopia (with macula sparing)
Cortical blindness
Visual agnosia
What are the features of a temporal lobe lesion?
Wernickes aphasia
Superior homonymous quadrantonopia
Auditory agnosia
Prosopagnosia (difficulty recognising faces)
What are the features of a frontal lobe lesion?
Broca’s (expressive) aphasia Disinhibition Perseveration Anosmia Inability to generate a list
What organisms cause meningitis in 0-3 months?
Group B streptococcus (most common)
E. Coli
Listeria monocytogenes
What organisms cause meningitis at 3 months to 6 years?
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilis influenzae
What organisms cause meningitis between 6 and 60?
Neisseria meningitidis
Streptococcus pneumoniae
In over 60 also listeria monocytogenes
What conditions cause renal tubular acidosis type 1?
Rheumatoid arthritis SLE sjogrens Amphoteracin b toxicity Analgesic nephropathy
What are the causes of dilated cardiomyopathy?
- idiopathic: the most common cause
- myocarditis: e.g. Coxsackie B, HIV, diphtheria, Chagas disease
- ischaemic heart disease
- peripartum
- hypertension
- iatrogenic: e.g. doxorubicin
- substance abuse: e.g. alcohol, cocaine
- inherited: either a familial genetic predisposition to DCM or a specific syndrome e.g. Duchenne muscular dystrophy
around a third of patients with DCM are thought to have a genetic predisposition
a large number of heterogeneous defects have been identified
the majority of defects are inherited in an autosomal dominant fashion although other patterns of inheritance are seen
infiltrative e.g. haemochromatosis, sarcoidosis
+ these causes may also lead to restrictive cardiomyopathy
nutritional e.g. wet beriberi (thiamine deficiency)
What are the following oncogenes associated with?
ABL c-MYC n-MYC BCL-2 RET RAS erb-B2
ABL
- Cytoplasmic tyrosine kinase
- Chronic myeloid leukaemia
c-MYC
- Transcription factor
- Burkitt’s lymphoma
n-MYC
- Transcription factor
- Neuroblastoma
BCL-2
- Apoptosis regulator protein
- Follicular lymphoma
RET
- Tyrosine kinase receptor
- Multiple endocrine neoplasia (types II and III)
RAS
- G-protein
- Many cancers especially pancreatic
- Also neurofibromatosis
erb-B2 (HER2/neu)
- Tyrosine kinase receptor
- Breast and ovarian cancer
What are the following tumour suppressor genes associated with?
p53 APC BRCA1 BRCA2 NF1 Rb WT1 Multiple tumor suppressor 1 (MTS-1, p16)
p53
-Common to many cancers, Li-Fraumeni syndrome
APC
Colorectal cancer
BRCA1
-Breast and ovarian cancer
BRCA2
-Breast and ovarian cancer
NF1
-Neurofibromatosis
Rb
-Retinoblastoma
WT1
-Wilm’s tumour
Multiple tumor suppressor 1 (MTS-1, p16)
-Melanoma
What are the causes of cushing’s syndrome and how are they divided?
ACTH dependent causes
- Cushing’s disease (80%): pituitary tumour secreting -ACTH producing adrenal hyperplasia
- ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes
ACTH independent causes
- iatrogenic: steroids
- adrenal adenoma (5-10%)
- adrenal carcinoma (rare)
- Carney complex: syndrome including cardiac myxoma
- micronodular adrenal dysplasia (very rare)
Pseudo-Cushing’s
- mimics Cushing’s
- often due to alcohol excess or severe depression
- causes false positive dexamethasone suppression test or -24 hr urinary free cortisol
- insulin stress test may be used to differentiate
What are the adverse effects of isotretinoin?
teratogenicity
-females should ideally be using two forms of contraception (e.g. Combined oral contraceptive pill and condoms)
dry skin, eyes and lips/mouth
-the most common side-effect of isotretinoin
low mood
-whilst this is a controversial topic, depression and other psychiatric problems are listed in the BNF
raised triglycerides
hair thinning
nose bleeds (caused by dryness of the nasal mucosa)
intracranial hypertension: isotretinoin treatment should not be combined with tetracyclines for this reason
photosensitivity
Name the Primary Immunodeficiencies categorised as B Cell disorders
B Cell Disorders
- Common variable immunodeficiency
- Bruton’s (x-linked) congenital agammaglobulinaemia
- Selective immunoglobulin A deficiency
Name the Primary Immunodeficiencies categorised as T cell disorders
T Cell Disorders
-Di George Syndrome
Name the primary immunodeficiencies categorised as Combined B- and T- cell disorders
Combined B- and T- Cell disorders
- Severe combined immunodeficiency
- Ataxic telangiectasia
- Wiskott-Aldrich Syndrome
- Hyper IgM syndromes
What are the stages of clinical trial?
I
- Determines pharmacokinetics and pharmacodynamics and side-effects prior to larger studies
- Conducted on healthy volunteers
II
- Assess efficacy + dosage
- Involves small number of patients affected by particular disease
- May be subdivided into
- -IIa - assesses optimal dosing
- -IIb - assesses efficacy
III
- Assess effectiveness
- Typically involves 100-1000’s of people, often as part of a randomised controlled trial, comparing new treatment with established treatments
IV
- Postmarketing surveillance
- Monitors for long-term effectiveness and side-effects
What drugs induce impaired glucose tolerance?
thiazides, furosemide (less common) steroids tacrolimus, ciclosporin interferon-alpha nicotinic acid antipsychotics
Beta-blockers cause a slight impairment of glucose tolerance. They should also be used with caution in diabetics as they can interfere with the metabolic and autonomic responses to hypoglycaemia
What drugs cause urinary retention?
tricyclic antidepressants e.g. amitriptyline anticholinergics opioids NSAIDs disopyramide
What are the causes of massive splenomegaly?
myelofibrosis chronic myeloid leukaemia visceral leishmaniasis (kala-azar) malaria Gaucher's syndrome
What drugs lengthen the QT interval?
amiodarone
ciprofloxacin
antipsychotics
tricyclic antidepressants
What are the causes of left axis deviation?
left anterior hemiblock
left bundle branch block
inferior myocardial infarction
Wolff-Parkinson-White syndrome* - right-sided accessory pathway
hyperkalaemia
congenital: ostium primum ASD, tricuspid atresia
minor LAD in obese people
What are the causes of right axis deviation?
right ventricular hypertrophy left posterior hemiblock lateral myocardial infarction chronic lung disease → cor pulmonale pulmonary embolism ostium secundum ASD Wolff-Parkinson-White syndrome* - left-sided accessory pathway normal in infant < 1 years old minor RAD in tall people
What condition is caused by Onchocerca volvulus?
Causes ‘river blindness’. Spread by female blackflies
Features include blindness, hyperpigmented skin and possible allergic reaction to microfilaria
rIVERblidness = IVERmectin
What are the causes of a loud S2?
Causes of a loud S2
- hypertension: systemic (loud A2) or pulmonary (loud P2)
- hyperdynamic states
- atrial septal defect without pulmonary hypertension
What are the side effects of amiodarone?
Thyroid dysfunction: both hyper and hypothyroidism Corneal deposits Pulmonary fibrosis/ pneumonitis Liver fibrosis / hepatitis Peripheral neuropathy, myopathy Photosensitivity "slate grey" appearance Thrombophlebitis and injection site reactions Bradycardia lengths QT interval
SLATE TAN
- Slate gray
- Liver damage
- Ataxia/ arrhythmias
- Thyroid dysfunction
- Eye/ corneal reversible microdeposits
- Taste disturbance
- Alveolitis
- Neuropathy
What infections occur at CD4 count 200-500?
Oral Thrush
Hairy Leukoplakia
Kaposi sarcoma
Shingles
What infections occur at CD4 count 100-200?
Cryptosporidiosis
-(Whilst patients with a CD4 count of 200-500 may develop cryptosporidiosis the disease is usually self-limiting and similar to that in immunocompetent hosts)
Cerebral toxoplasmosis
Progressive multifocal leukoencephalopathy
-(Secondary to the JC virus)
Pneumocystis jirovecii pneumonia
HIV dementia
What infections occur at CD4 count 50-100?
Aspergillosis
-(Secondary to Aspergillus fumigatus)
Oesophageal candidiasis
-(Secondary to Candida albicans)
Cryptococcal meningitis
Primary CNS lymphoma
-(Secondary to EBV)
What infections occur at CD4 count <50?
Cytomegalovirus retinitis
-(Affects around 30-40% of patients with CD4 < 50 cells/mm³)
Mycobacterium avium-intracellulare infection
Name the common autosomal recessive conditions
Albinism Ataxic telangiectasia Congenital adrenal hyperplasia Cystic fibrosis Cystinuria Familial Mediterranean Fever Fanconi anaemia Friedreich's ataxia Gilbert's syndrome* Glycogen storage disease Haemochromatosis Homocystinuria Lipid storage disease: Tay-Sach's, Gaucher, Niemann-Pick Mucopolysaccharidoses: Hurler's PKU Sickle cell anaemia Thalassaemias Wilson's disease
What is the equation for sensitivity?
Sensitivity
TP / (TP + FN )
Proportion of patients with the condition who have a positive test result
TP = True Positive FN = False Negative
What is the equation for specificity?
Specificity
TN / (TN + FP)
Proportion of patients without the condition who have a negative test result
TN = True Negative FP = False Positive
What is the equation for positive predictive value?
Positive predictive value
TP / (TP + FP)
The chance that the patient has the condition if the diagnostic test is positive
TP = True Positive FP = False Positive
What is the equation for negative predictive value?
Negative predictive value
TN / (TN + FN)
The chance that the patient does not have the condition if the diagnostic test is negative
TN = True Negative FN = False Negative
What is the equation for likelihood ratio for a positive test result?
Likelihood ratio for a positive test result
sensitivity / (1 - specificity)
How much the odds of the disease increase when a test is positive
What is the equation for likelihood ratio for a negative test result?
Likelihood ratio for a negative test result
(1 - sensitivity) / specificity
How much the odds of the disease decrease when a test is negative
What are the clinical features of Alport Syndrome?
- Microscopic haematuria
- Progressive renal failure
- Bilateral sensorineural deafness
- Lenticonus: protrusion of the lens surface into the anterior chamber
- Retinitis pigmentosa
- Renal biopsy: splitting of lamina densa seen on electron microscopy
What are the stages of the cardiac action potential?
0
- Rapid depolarisation
- Rapid sodium influx
- These channels automatically deactivate after a few ms
1
- Early repolarisation
- Efflux of potassium
2
- Plateau
- Slow influx of calcium
3
- Final repolarisation
- Efflux of potassium
4
- 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
What are the causes of Type 2 RTA?
idiopathic, as part of Fanconi syndrome, Wilson's disease, cystinosis, outdated tetracyclines, carbonic anhydrase inhibitors (acetazolamide, topiramate)
What are the clinical features of tuberous sclerosis?
Cutaneous features
- depigmented ‘ash-leaf’ spots which fluoresce under UV light
- roughened patches of skin over lumbar spine (Shagreen patches)
- adenoma sebaceum (angiofibromas): butterfly distribution over nose
- fibromata beneath nails (subungual fibromata)
- café-au-lait spots* may be seen
Neurological features
- developmental delay
- epilepsy (infantile spasms or partial)
- intellectual impairment
Also
- retinal hamartomas: dense white areas on retina (phakomata)
- rhabdomyomas of the heart
- gliomatous changes can occur in the brain lesions
- polycystic kidneys, renal angiomyolipomata
- lymphangioleiomyomatosis: multiple lung cysts
What are the clinical features and treatment of organophosphate insecticide poisoning?
Features can be predicted by the accumulation of acetylcholine (mnemonic = SLUD)
- Salivation
- Lacrimation
- Urination
- Defecation/diarrhoea
cardiovascular: hypotension, bradycardia
also: small pupils, muscle fasciculation
Management
- atropine
- the role of pralidoxime is still unclear - meta-analyses to date have failed to show any clear benefit
What is the initial blind therapy of infective endocarditis?
Native valve
amoxicillin, consider adding low-dose gentamicin
If penicillin allergic, MRSA or severe sepsis
vancomycin + low-dose gentamicin
If prosthetic valve
vancomycin + rifampicin + low-dose gentamicin
What are the causes of raised prolactin?
Prolactinoma Pregnancy Oestrogens Physiological (Stress, exercise, sleep) Acromegaly (1/3 of patients) PCOS Primary hypothyroidism (due to TRH stimulating prolactin release
Drug causes:
-Metoclopromide, domperidone
Phenothiazines
haloperidol
What causes increased BNP levels?
left ventricular hypertrophy ischaemia tachycardia right ventricular overload hypoxaemia (including PE) GFR <60 Sepsis COPD Diabetes Age >70 Liver cirrhosis
What causes decreased BNP levels?
Obesity Diuretics ACEi/ ARBs B blockers Aldosterone antagonists
What are the causes of restrictive cardiomyopathy?
Amyloidosis (e.g. secondary to myeloma) - most common cause in UK
Haemochromatosis
Post radiation fibrosis
Loffler’s syndrome
-endomyocardial fibrosis with a prominent eosinophillic infiltrate
Endocardial fibroelastosis
- Thick fibroelastic tissue forms in the endocardium
- Most commonly seen in young children
Sarcoidosis
Scleroderma
What is the management of ITP?
Platelet >30 - Observe
Platelet <30 - ORAL prednisolone
Emergency treatment (life threatening or organ threatening bleeding -Platelet transfusion, IV methylprednisolone and IV immunogolulin
What are the causes of cranial Diabetes insipidus?
idiopathic post head injury pituitary surgery craniopharyngiomas histiocytosis x DIDMOAD (Wolfram's syndrome) Haemochromatosis
What is macrophage activation syndrome?
Uncontrolled hyper-inflammatory state associated with many systemic autoimmune diseases but in particular JIA.
ACR/EULAR classification criteria for macrophage activation syndrome (MAS) state that in a patient with JIA who presents with a fever, a diagnosis of MAS can be made if the ferritin level is > 684 ng/ml and any two of the following are present (platelets < 181 * 109/L, AST > 48 U/L, triglycerides > 156 mg/dl, fibrinogen < 360 mg/dl).
Refractory fever and hepatosplenomegaly are typical clinical features.
Interferon-gamma is responsible for the activation of macrophages and is heavily implicated in the pathogenesis of this condition.
What is the incidence of down’s syndrome by age?
30 years 1/1000
35 years 1/300
40 years 1/100
45 years 1/30
Divide by 30 for each 5 years
What are the different types of thyroid cancer?
Papillary carcinoma (70%)
- Usually contain a mixture of papillary and colloidal filled follicles
- Histologically tumour has papillary projections and pale empty nuclei
- Seldom encapsulated
- Lymph node metastasis predominate
- Haematogenous metastasis rare
Follicular adenoma (20% for all follicular)
- Usually present as a solitary thyroid nodule
- Malignancy can only be excluded on formal histological assessment
- Follicular carcinoma
- May appear macroscopically encapsulated, microscopically capsular invasion is seen. Without this finding the lesion is a follicular adenoma.
- Vascular invasion predominates
- Multifocal disease raree
Medullary carcinoma
- C cells derived from neural crest and not thyroid tissue
- Serum calcitonin levels often raised
- Familial genetic disease accounts for up to 20% cases
- Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.
Anaplastic carcinoma (1%)
- Most common in elderly females
- Local invasion is a common feature
- Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy.
- Chemotherapy is ineffective.
Lymphoma (rare)
-Associated with hashimoto’s thyroiditis
What may precipitate lithium toxicity?
dehydration
renal failure
drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
What are the features of Wernicke’s Encephalopathy?
A useful mnemonic to remember the features of Wernicke’s encephalopathy is CAN OPEN
Confusion Ataxia Nystagmus Ophthamoplegia PEripheral Neuropathy
When do you give dexamethasone for meningitis?
NICE guidelines recommend treating bacterial meningitis with dexamethasone if lumbar puncture reveals either: purulent CSF, white cell count > 1000 cells/µL, raised white cell count plus protein count > 1g/L, or bacteria on gram stain. Dexamethasone should be given within 4 hours of starting antibiotics and should be avoided if the duration from starting antibiotics is beyond 12 hours.
What is cardiac syndrome X?
Cardiac syndrome X - also called microvascular angina. Patients have a normal ECG at rest and normal coronary arteries but develop ST depression on exercise stress testing.
What are the diagnostic criteria for tumour lysis syndrome?
From 2004 TLS has been graded using the Cairo-Bishop scoring system -
Laboratory tumor lysis syndrome: abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy.
- uric acid > 475umol/l or 25% increase
- potassium > 6 mmol/l or 25% increase
- phosphate > 1.125mmol/l or 25% increase
- calcium < 1.75mmol/l or 25% decrease
Clinical tumor lysis syndrome: laboratory tumour lysis syndrome plus one or more of the following:
- increased serum creatinine (1.5 times upper limit of normal)
- cardiac arrhythmia or sudden death
- seizure
What are the most common causes of endocarditis?
Staphylococcus aureus
Staphylococcus epidermidis if < 2 months post valve surgery
What are the features of MEN type 1?
Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia
Pituitary (70%)
Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)
Also: adrenal and thyroid
What are the features of MEN type IIa?
Medullary thyroid cancer (70%)
2 P’s
Parathyroid (60%)
Phaeochromocytoma
What are the features of MEN type IIb
Medullary thyroid cancer
1 P
Phaeochromocytoma
Marfanoid body habitus
Neuromas
What is the management of trigeminal neuralgia?
carbamazepine is first-line
failure to respond to treatment or atypical features (e.g. < 50 years old) should prompt referral to neurology
What is anakinra?
Anakinra is an interleukin-1 (IL-1) receptor antagonist. Interleukin-1 refers to a ‘superfamily’ of 11 cytokines that are responsible for acute inflammation and inducing fever. Blocking IL-1 with anakinra is beneficial in pro-inflammatory conditions such as rheumatoid arthritis. Il-1 is predominantly secreted by macrophages.
What are human herpes virus (HHV):
HHV 2 HHV 3 HHV 4 HHV 5 HHV 6 and 7 HHV 8
Human herpesvirus virus 2 (HHV-2) also commonly known as herpes simplex virus-2 (HSV-2) causes oral and/or genital herpes, therefore this is the incorrect answer in this case.
Human herpesvirus virus 3 (HHV-3) also commonly known as varicella-zoster virus (VZV) causes chickenpox and shingles, therefore this is the incorrect answer in this case.
Human herpesvirus virus 4 (HHV-4) also commonly known as Epstein–Barr virus (EBV) causes Epstein-Barr virus-associated lymphoproliferative diseases, therefore this is the incorrect answer in this case.
Pityriasis rosea is associated with the reactivation of herpesviruses 6 and 7. Influenza viruses and vaccines have triggered pityriasis rosea in some cases. The herald patch is a single plaque that appears 1–20 days prior to the generalised rash of pityriasis rosea.
Human herpesvirus virus 8 (HHV-8) also commonly known as Kaposi’s sarcoma-associated herpesvirus causes Kaposi’s sarcoma, therefore this is the incorrect answer in this case.
t(9;22) is seen in which malignancy?
t(9;22) - Philadelphia chromosome
present in > 95% of patients with CML
this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22
the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal
poor prognostic indicator in ALL
t(15;17) is seen in which malignancy?
t(15;17)
seen in acute promyelocytic leukaemia (M3)
fusion of PML and RAR-alpha genes
t(8;14) is seen in which malignancy?
t(8;14)
seen in Burkitt’s lymphoma
MYC oncogene is translocated to an immunoglobulin gene
t(11;14) is seen in which malignancy?
t(11;14)
Mantle cell lymphoma
deregulation of the cyclin D1 (BCL-1) gene
t(14;18) is seen in which malignancy?
t(14;18)
follicular lymphoma (seen in 90%)
increased BCL-2 transcription
What are the different strengths of steroid creams and give examples
Mild
-Hydrocortisone 0.5-2.5%
Moderate
- Betamethasone valerate 0.025% (Betnovate RD)
- Clobetasone butyrate 0.05% (Eumovate)
Potent
- Fluticasone propionate 0.05% (Cutivate)
- Betamethasone valerate 0.1% (Betnovate)
Very Potent
-Clobetasol propionate 0.05% (Dermovate)
What are the side effects of the TB drugs?
Rifampicin
- mechanism of action: inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
- potent liver enzyme inducer
- hepatitis, orange secretions
- flu-like symptoms
Isoniazid
- mechanism of action: inhibits mycolic acid synthesis
- peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
- hepatitis, agranulocytosis
- liver enzyme inhibitor
Pyrazinamide
- mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
- hyperuricaemia causing gout
- arthralgia, myalgia
- hepatitis
Ethambutol
- mechanism of action: inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan
- optic neuritis: check visual acuity before and during treatment
- dose needs adjusting in patients with renal impairment
Give 2 sulphonureas
glimepiride and glipizide
What is the mechanism of action of Dipyridamole?
inhibits phosphodiesterase, elevating platelet cAMP levels which in turn reduce intracellular calcium levels
other actions include reducing cellular uptake of adenosine and inhibition of thromboxane synthase
What organisms are splenectomy patients vulnerable to?
Yes Some Nasty Killer Bacteria Have Some Capsule(2) Protection….
Yesenia S.pneumonia N.meningitidis K.pneumonia Bacillus H.influenza (not covered by Pen V) S.typhi Clostridium and C.neoformans P.aeruginosa
How do you treat chronic plaque psoriasis?
regular emollients may help to reduce scale loss and reduce pruritus
first-line: NICE recommend:
- a potent corticosteroid applied once daily plus vitamin D analogue applied once daily
- should be applied separately, one in the morning and the other in the evening)
- for up to 4 weeks as initial treatment
second-line: if no improvement after 8 weeks then offer:
-a vitamin D analogue twice daily
third-line: if no improvement after 8-12 weeks then offer either:
-a potent corticosteroid applied twice daily for up to 4 weeks, or
-a coal tar preparation applied once or twice daily
short-acting dithranol can also be used
How can you divide hypokalaemia and blood pressure?
Hypokalaemia with hypertension
- Cushing’s syndrome
- Conn’s syndrome (primary hyperaldosteronism)
- Liddle’s syndrome
- 11-beta hydroxylase deficiency*
Carbenoxolone, an anti-ulcer drug, and liquorice excess can potentially cause hypokalaemia associated with hypertension
Hypokalaemia without hypertension
- diuretics
- GI loss (e.g. Diarrhoea, vomiting)
- renal tubular acidosis (type 1 and 2**)
- Bartter’s syndrome
- Gitelman syndrome
What is the treatment for acromegaly?
Trans-sphenoidal surgery is the first-line treatment for acromegaly in the majority of patients.
If a pituitary tumour is inoperable or surgery unsuccessful then medication may be indicated:
somatostatin analogue
directly inhibits the release of growth hormone
for example octreotide
effective in 50-70% of patients
pegvisomant
GH receptor antagonist - prevents dimerization of the GH receptor
once daily s/c administration
very effective - decreases IGF-1 levels in 90% of patients to normal
doesn’t reduce tumour volume therefore surgery still needed if mass effect
dopamine agonists
for example bromocriptine
the first effective medical treatment for acromegaly, however now superseded by somatostatin analogues
effective only in a minority of patients
External irradiation is sometimes used for older patients or following failed surgical/medical treatment
What are the tumour in Von Hippel Lindau syndrome?
PEE BREAK
Pancreas (benign cystic or malignant neurendocrine) Epididymal cystadenomas Endolymphatic sac (inner ear)
Brain (CNS haemangioblastoma in 70%)
Retinal haemangioblastoma (in 60%)
Ears (enodlymphatic sac as above, just to make the mnemonic work lol)
Adrenal (phaeochromocytoma, may be intra- or extra-adrenal)
Kidney (RCC and cystic)
What drugs must be stopped in pregnancy?
Antibiotics
- tetracyclines
- aminoglycosides
- sulphonamides and trimethoprim
- quinolones: the BNF advises to avoid due to arthropathy in some animal studies
Other drugs
- ACE inhibitors, angiotensin II receptor antagonists
- statins
- warfarin
- sulfonylureas
- retinoids (including topical)
- cytotoxic agents
- Bosentan
What are the clinical features of polyarteritis nodosa?
- fever, malaise, arthralgia
- weight loss
- hypertension
- mononeuritis multiplex, sensorimotor polyneuropathy
- testicular pain
- livedo reticularis
- haematuria, renal failure
- perinuclear-antineutrophil cytoplasmic antibodies (ANCA) -are found in around 20% of patients with ‘classic’ PAN
- hepatitis B serology positive in 30% of patients
What is the mechanism of action of baclofen?
Baclofen is an agonist of GABA receptors and is used as a muscle relaxant to treat spasticity conditions such as multiple sclerosis and cerebral palsy.
What is the mechanism of action of flumazenil.
An example of a GABA antagonist is flumazenil. Baclofen is an agonist rather than antagonist at GABA receptors.
What is the mechanism of action of buscopan?
Muscarinic M3 receptor antagonist is buscopan, used to treat pain associated with bowel wall spasm and respiratory secretions during end-of-life care
What are the trinucleotide repeats for:
- Huntington’s disease
- Friedrich Ataxia
- Myotonic dystrophy
- Fragile X syndrome
CAG: Huntington’s disease
GAA: Friedrich Ataxia
CTG: Myotonic dystrophy
CGG: Fragile X syndrome
Give an example of entry inhibitors in HIV.
When are they used?
Maraviroc (binds to CCR5, preventing an interaction with gp41),
Enfuvirtide (binds to gp41, also known as a ‘fusion inhibitor’)
Prevent HIV-1 from entering and infecting immune cells
Tend to be used in patients with treatment-resistant HIV with persistent high viral load and/or low CD4 count.
What area of the brain if affected in internuclear opthalmoplegia?
The medial longitudinal fasciculus is located in the paramedian area of the midbrain and pons
What drugs exacerbate myasthenia gravis?
penicillamine quinidine, procainamide beta-blockers lithium phenytoin antibiotics: gentamicin, macrolides, quinolones, tetracyclines
What is the highest to lowest proportions of immunoglobulins found in blood?
GAMDE
Give an example of alkylating chemotherapy.
What is its mechanism of action and side effect?
Cyclophosphamide
Alkylating agent - causes cross-linking in DNA
Haemorrhagic cystitis, myelosuppression, transitional cell carcinoma
What is the mechanism of action of anthracyclines?
Give an example
Anthracyclines (e.g doxorubicin)
Stabilizes DNA-topoisomerase II complex inhibits DNA & RNA synthesis
Cardiomyopathy
What is the mechanism of action of fluorouracil (5-FU)?
Pyrimidine analogue inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase)
What is the mechanism of action of 6-mercaptopurine?
Purine analogue that is activated by HGPRTase, decreasing purine synthesis
What is the mechanism of action of cytarabine?
Pyrimidine antagonist.
Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase
What are the causes of membranous glomerulonephropathy?
Membranous nephropathy is split into two main causes - primary and secondary. Primary membranous nephropathy is most commonly associated with anti-PLA2R antibodies.
Secondary membranous nephropathy means another process is linked with its development. The most common processes are:
- Malignancy such as solid tumours (lung, colon, breast, kidney)
- Infections: hepatitis B or C, HIV, malaria, syphilis, schistosomiasis
- Autoimmune diseases: SLE, sarcoidosis, IBD
- Drugs: NSAID’s, captopril, gold, penicillamine, lithium, clopidogrel
What is the genetics of Autosomal polycystic kidney disease?
ADPKD Type 1
- 85% of cases
- Chromosome 16
- Presents with renal failure earlier
ADPKD Type 2
- 15% of cases
- Chromosome 4
What is the treatment for Tetanus?
Metronidazole is now preferred to benzylpenicillin
What is the mechanism of action or irinotecan?
Inhibition of topoisomerase I. By doing so, it prevents the relaxation of supercoiled DNA.
Adverse effects include myelosuppression.
It is usually used for colon cancer.
What are the poor prognostic factors in Rheumatoid arthritis?
Rheumatoid factor positive Anti-CCP antibodies Poor functional status at presentation X-ray: early erosions (e.g. after <2 years) Extra articulate features e.g. nodes HLA DR4 Insidious onset
What are the Kings’s College Hospital criteria for liver transplantation?
Arterial pH < 7.3, 24 hours after ingestion
Or all of the following
- Prothrombin time >100 seconds
- Creatinine > 300
- Grade III or IV encephalopathy
What foods are high in potassium?
Avoid in renal failure
Bananas Oranges Kiwi fruit Avocado Spinach Tomatoes
What is associated with HLA-A3?
Haemachromatosis
What is associated with HLA-B51?
Behçet’s disease
What is associated with HLA-B27?
Ankylosis spondylitis
Reactive arthritis
Acute anterior uveitis
What is associated with HLA-DQ2/DQ8?
Coeliac disease
What is associated with HLA-DR2?
Narcolepsy
Goodpasture’s
What is associated with HLA-DR4
Type 1 DM (also associated with DR3 but more strongly DR4) Rheumatoid arthritis (in particular the DRB1 gene)
What are the features of subacute combined degeneration of the cord?
What are nervous system areas they relate to?
Damage to posterior columns
- loss of proprioception, light touch and vibration sensation (sensory ataxia and positive Romberg’s test)
Damage to lateral columns
- spastic weakness and up going planters (UMN signs)
Damage to peripheral nerves
- absent ankle and knee jerks (LMN signs)
What does C1 deficiency cause?
Hereditary angioedema
C1-INH is a multi factorial serine protease inhibitor
Probable mechanism is uncontrolled release of bradykinin resulting in oedema in tissues
C1q, C1rs, C2, C4 deficiency (classical pathway components) cause what?
Immune complex disease
E.g. SLE, henoch-schonlein purpura
C3 deficiency causes what?
Recurrent bacterial infections
C5-9 deficiency causes what?
Encodes the membrane attack complex (MAC)
Particularly prone to Neisseria meningitidis infection
What is the mechanism of action of cyclosporin?
Ciclosporin is an immunosuppressant which decreases clonal proliferation of T cells by reducing IL-2 release. It acts by binding to cyclophilin forming a complex which inhibits calcineurin, a phosphatase that activates various transcription factors in T cells
What are the indications for a ICD?
long QT syndrome hypertrophic obstructive cardiomyopathy previous cardiac arrest due to VT/VF previous myocardial infarction with non-sustained VT on 24 hr monitoring, inducible VT on electrophysiology testing and ejection fraction < 35% Brugada syndrome
