RACP Flashcards
What is Cotinine?
Metabolic product of nicotine - provides quantifiable method of assessing nicotine exposure (via smoking, passive, or NRT). Detectable in blood, saliva or urine.
What is the DECAF score?
What are its components?
Score used to assess COPD exacerbations ?home vs inpatient management.
Score 0-1 –> early dc
Score 2 = intermediate
Score >= 3 –> admit / palliate
Components:
- eMRC dyspnoea scale on typical day (2 points if too dyspnoeic to leave house)
- eosinophils
- consolidation on CXR
- acidaemia (pH <7.30)
- presence of AF
What is Loeffler Syndrome?
Transient passage of helminth larvae (mainly Ascaris) from blood to alveoli through to proximal airways and then into digestive tract. Manifest on CXR as migrating / self-resolving opacities. Associated with blood eosinophilia.
Which cells produce surfactant?
Type 2 pneumocytes
Cause of non-infective endocarditis
Libman-sacks disease (from SLE)
Bohr Effect
Increase in acidity (decrease pH) or increased pCO2 in a tissue causes RIGHT shift –> decreased O2 affinity –> increased O2 delivery to metabolically-active tissue.
Haldane Effect
Increased oxygen binding makes CO2/H+ bind less well to Hb molecule (increases CO2 delivery to the lungs)
Zero Order Kinetics
Clearance by easily saturated enzyme system. Once saturated, the rate of clearance plateaus, and does not vary no matter how much drug is present. Results in a constant rate of elimination predisposing to high levels of the drug and toxicity.
Examples: phenytoin, alcohol and salicylates.
First Order Kinetics
Linear process, where the rate of elimination is proportional to the drug concentration. This means that the higher the drug concentration, the higher its elimination rate.
What is Pompholyx?
Eczema of soles of hands / feet.
Often triggered by heat / humidity.
Amiodarone-induced Thyrotoxicosis:
Type 1 vs Type 2
Type 1:
Excess iodine load –> excess thyroid hormone made
Goitre present
Rx = carbimazole
Type 2:
Destructive thyroiditis
No goitre
Rx = prednisone
Key Stain for Lymphoblasts (ALL)
TdT (staining for DNA polymerase)
Key surface markers for B cells
CD10, CD19, CD20
Acute Promyelocytic Leukaemia
- Marker
- Key Receptor
- Key Complication
- Treatment
t(15;17)
Retinoic acid receptor
Widespread DIC
All-trans retinoic acid (ATRA) –> encourages cell differentiation
Auer Rods
Crystal ‘rod’ seen in myeloblasts in AML
Definition of ‘pulmonary nodule’
<3cm lesion, completely surrounded by lung parenchyma.
Larger lesions called ‘masses’
Most common causes of benign lung nodules (2)
Infectious granulomas
Pulmonary harmartomas
Criteria for not further following up a pulmonary nodule (2)
Initial size <6mm (i.e. =<5mm) (and no other high risk features)
OR
No growth over 2 years
Diagnosing BK Nephropathy:
- Typical approach
- Gold standard approach
- Viral load (via PCR) in context of allograft dysfunction
2. Renal biopsy (especially if DDx includes transplant rejection, which has opposite management approach…)
Eculizumab:
- MoA
- Indications
Binds C5 (i.e. the terminal complement component) - prevents formation / activation of C5a and C5b
PNH, aHUS, NMO (if anti-AQP4 +)
Emicizumab
- Indication
- MoA
Haemophilia A
Cross-links F9a and F10 –> leading to F10a formation. (F10a then converts prothrombin –> thrombin, (along with F5)).
Clopidogrel Mechanism
Irreversibly inhibits P2Y12 of ADP receptors on platelets → prevents activation of GPIIb/IIIa complex → no fibrinogen cross-linking → no platelet aggregation
(Whereas ticagrelor is reversible)
HIV Binding Molecules
GP 120 on virus –> CD4 on host
Then GP41 –> CCR5 (acute) or CXCR4 (chronic)
HIV Protective HLA and mechanism
HLA B57*01
Allows binding of MHC-1 to HIV core protein (which can not be mutated) –> strong CD8 response –> slower progression to AIDS (and less hypersensitivity to Abacavir)
HIV Prophylaxis cut-offs and drug to use
- PJP
- Cryptococcus
PJP; give cotrimoxazole if CD4 count <200
Cryptococcys; give fluconazole if CD4 count <100
HIV pre-exposure prophylaxis medications
Tenofovir + emtracitibine given daily
HIV post-exposure prophylaxis (3)
Must be started <72h, 28 day course
If risk <1 / 1,000 –> 2x drug therapy (tenofovir + emtracitabine / lamivudine)
If risk >1 / 1,000 –> 3x drug therapy (2x drug Rx + dolutegravir)
Rasburicase - mechanism, caution scenario
Supplies uricase enzyme
Converts uric acid to allantoin (water soluble –> renal clearance)
- I.e. can acutely LOWER urate concentration (whereas allopurinol just stops production)
Caution in G6PD deficiency
Azathioprine Metabolism
Active compound = 6-TGN
- Levels > 235 a/w better clinical response (but more myelotoxicity)
Inactive metabolite = 6-MMP
- Levels > 5,700 a/w hepatotoxicity
Conversion to 6-MMP can be reduced by allopurinol - give for ‘shunters’ / hypermethylators
Check TPMT enzyme beforehand
Binding site in Heparin-induced Thrombocytopaenia (HIT)
Antibodies against heparin-platelet factor 4 complex
which can also activate platelets, leading to thrombotic tendency
Kings College Criteria for Liver Transplant (Paracetamol OD)
Arterial pH <7.30
Or all of:
- PT >100sec (INR > 6.5)
- Creatinine > 300
- Grade 3 or 4 encephalopathy
(Whereas PT >100sec = absolute criteria for non-paracetamol liver failure)
G6PD Inheritance Pattern
X-linked recessive
Tocilizumab Mechanism
Binds soluble- and membrane-bound IL-6 receptors
Rheumatoid Arthritis Susceptibility Genes
HLA-DRB1
Subtypes (i.e. different alleles of DRB1):
HLA-DRB104:01 and HLA-DRB104:04
RA: Shared epitope concept
HLA alleles that confer increased risk for RA all have similar amino acid sequence at position 70-74 (even in completely different HLA subtypes).
(QKRAA)
RF vs ACPA; which has stronger correlation with extraarticular disease severity?
RF - e.g. ILD, vasculitis
Whereas ACPAs predict more severe/erosive articular damage
Antiphospholipid Abs
Anti-cardiolipin
Lupus anticoagulant
Anti-beta-2-glycoprotein
(Need to be present in serum on 2x occasions at least 12 weeks apart)
Most specific auto-antibody for SLE
Anti-Sm
Auto-antibody that goes up/down with SLE disease severity e.g. nephritis, vasculitis
Anti-dsDNA
Th1 cytokines
IFNy
IL-2
IL-3
Th2 cytokines
IL-4 IL-5 IL-6 IL-10 IL-13 TGF-beta
Tumour markers:
- Ovarian cancer
- Breast cancer
- Pancreatic cancer
CA12-5
CA15-3
CA19-9
Half life formula
T1/2 = 0.693 x Vd/CL
Can be rearranged to give CL value, units L/h
Anti-phospholipase A2 Receptor Antibodies are associated with which GN?
(Anti-PLAR2)
Idiopathic Membranous GN
Key CJD features (3)
Rapid dementia
Myoclonus
Periodic, triphasic sharp waves on EEG
VZV post-exposure prophylaxis
Immunocompetent –> VZV vaccine
Immunocompromised –> VZV Ig (within 10 days)
Medications causing acute interstitial nephritis (3)
PPIs
Antibiotics
NSAIDs
Key test for urea cycle disorders
Elevated ammonia (with normal BSL and anion gap)
Aprepitent receptor target
Neurokinin 1 Receptor –> blocks substance P
Used for pruritis and chemo-induced N+V
BRCA gene inheritance
Autosomal dominant
Syphilis cardiolipin tests / ‘non-treponemal’ tests
VDRL and RPR
Become negative after treatment, used for monitoring treatment / recurrence
Syphilis ‘treponemal’ tests (3,1)
E.g. Treponema pallidum haemagglutination test (TPHA)
Enzyme immunoassay (EIA)
T. pallidum particle agglutination test (TPPA)
Stay positive after treatment
Most common cause of inherited thrombophilia
Factor V Leiden (activated protein C resistance)
Due to mutation, protein C can not inactivate factor 5 –> procoagulant status
(Protein C normally inactivates F5 and F8)
Extra-intestinal IBD features associated with disease activity (4)
Pauciarticular arthritis (asymmetric) / large joint
Erythema nodosum
Episcleritis
Osteoporosis
Extra-intestinal IBD features NOT associated with disease activity (5)
'APUPS': Axial / ank spond Pyoderma gangrenosum Uveitis PSC Symmetric, small joint (polyarticular) arthritis
Key areas for lesions on MRI in MS diagnosis
Periventricular - ‘Dawson’s fingers’
Juxtacortical - ‘U fibre’ / cortical
Infratentorial (cf. vascular)
Spinal cord
ESCAPPM Organisms
- Definition
- Transmission of resistance
- Management (2)
- Organisms
ESBL Subgroup with inducible beta-lactamase activity
AmpC chromosomally-mediated
Management:
Carbapenems
Piptaz
Enterobacter species Serratia spp Citrobacter freundii (and braakii) Acinetobacter and Aeromonas spp Proteus (not mirabilis) Providencia spp Morganella morganii
Ann Arbor Staging
I - single node
II - 2x nodes on same side of diaphragm
III - nodes on either side of diaphragm
IV - extra-lymphatic organ involved
A - no systemic Sx (other than pruritis)
B - >10% weight loss, fever, night sweats
AML poor prognosis markers (2)
Deletions of chromosomes 5 or 7,
FLT3
Pendred syndrome
Autosomal recessive
Bilateral SNHL + hypothyroidism + goitre
MRI shows 1.5 turns of cochlea (cf 2.5)
Rx = thyroxine and hearing aids
In what ILD would biopsy show hyaline membranes?
Acute interstitial pneumonia
What is the main determinant of drug plasma concentration at steady state?
Drug clearance
MODY3 mutation
HNF1a
Most common form of MODY
MODY2 mutation
glucokinase
MODY1 mutation
HNF4a
Define nonsense mutation
Base change that causes a stop codon
Mutation in MDS with good prognosis
Deletion (5q) - responds to lenalidomide
Gitleman syndrome
Defect in distal tubule Na/Cl transporter, like being on a thiazide
Bartter syndrome
Defect in thick ascending limb Na-K-2Cl transporter, like being on frusemide
Liddle syndrome (3)
Gain of function mutation –> ENaC can no longer be broken down –> excess sodium absorption / potassium loss –> HTN / hypo-K / alkalosis
Hyper-aldosterone-like state, (but low renin AND low aldosterone levels (cf. Conn’s))
Spironolactone not effective in Rx (use amiloride or triamterene which block ENaC). Salt restriction also effective at maintaining normal sodium / bicarb levels.
Autosomal dominant
Gefitinib mechanism
EGFR inhibitor - used in lung adenoca.
Well’s criteria for PE (7) + scores
PE leading DDx - 3 Limb swelling - 3 HR > 100 - 1.5 Immobilisation - 1.5 Previous PE - 1.5 Haemoptyisis - 1 Malignancy - 1
Acute Interstitial Nephritis urine findings
+ve white cells
- ve red cells
- ve protein
Ipilimumab mechanism
Inhibition of CTLA-4 co-stimulator on T-cells / Treg cells
MRI ‘hummingbird sign’ is seen in…
PSP (due to midbrain atrophy)
Pre-op insulin: prior to major surgery
Give IV insulin at variable rate
True/False: correcting vitamin D deficiency may help prevent SLE flares?
True
Anion gap formula
(Na + K) - (Cl + HCO3)
Ref range 4 - 12
If high, implies presence of unaccounted for anions (that have consumed bicarb)
True/False: osteoarthritis is a risk factor for osteoporosis?
False (may even be protective)
Predictor of reactive arthritis recurrence or persistance
HLA-B27 gene
ACEi benefits:
- Renal
- Ophthal
If microalbuminuria, then ACEi/ARB slow progression to proteinuria (may initially see a creatinine rise)
If no microalbuminuria, there is no renal benefit but protects against retinopathy
Implication of decreasing insulin requirement in GDM
Could suggest placental failure (the placenta is often a cause of insulin resistance) –> needs obstetric input
What agent causes cold-aggravated neuropathy?
Oxaliplatin (via voltage-gated Na channels)
Maternal / peripartum HIV management
Mum should be on ART regardless of HIV load
Intrapartum Zidovudine if HIV RNA > 1,000
Infant should receive PEP
No breast feeding
C-section if maternal HIV RNA >400 at 36/40
SAAG interpretation
SAAG > 11 = portal HTN
i.e. despite high oncotic pressure, there is still ascites forming indicating the presence of hydrostatic pressure
Acanthocytes
- AKA
- Describe appearance
- Commonly found in…
AKA spur cells
Large red cell with spike-like projections
Severe liver disease
Light microscopy: ‘sub-epithelial deposits’ are seen in:
Membranous nephropathy
AKA spike and dome appearance
Gram negative cocci species (2)
Neisseria
Moraxella
Horner’s / eye sympathetic chain anatomy / neuron orders
1st order: posterior hypothalamus to spinal cord (ciliospinal centre of Budge) at C8-T2
2nd order: fibres exit at T1, cross lung apex, ascend in cervical sympathetic chain, terminate at superior cervical ganglion at level of bifurcation of common carotid artery (C3-4)
3rd order: ascend along internal carotid artery to eye
Mifepristone:
- Mechanism
- Use
Glucocorticoid receptor antagonist
Hyperglycaemia of Cushing’s
Ketoconazole use in adrenal disease:
- Mechanism
Inhibits androgen synthesis
Ambrisentan mechanism
Endothlin A + B ANTAGONIST
Sildenafil mechanism
Inhibits PDE-5
Riociguat mechanism
Sensitises guanlate cyclase to NO / activates gunalate cyclase
Iloprost mechanism
Prostaglandin analogue
Cell type activated in HLH
Macrophages (failed elimination by NK cells / CTLs)
Define: fraction excreted unchanged (Fe)
Proportion of active drug cleared renally in healthy person.
Genetic defect in Autoimmune Polyendocrine Syndrome type 1 (AKA APECED)
AIRE - involved in regulating T-cell selection in the thymus
Cell surface markers of Reed-Sternberg cells
CD15 (75%) and CD30 (100%)
RS cell is a ‘crippled’ germinal center B cell that has non-functional IgG gene arrangement
Pembrolizumab and Nivolumab mechanism
Inhibits PD-1
Adrenal gland zones / hormone synthesised (4)
Zona glomerulosa - mineralocorticoids
Zona fasciculata - glucocorticoids
Zona reticularis - androgens
Medulla - catecholamines
PBC associated diseases (2)
Sjogrens
Autoimmune thyroid disease
MRCP / ERCP ‘string of beads’ pattern refers to:
PSC
Multiple strictures in the biliary system
Red Man Syndrome mechanism
Direct mast cell stimulation by vancomycin –> histamine release
Castleman disease - characteristic finding:
Elevated IL-6
Treatment of latent TB (3)
3/12 of rifampicin + isoniazid (+pyridoxine)
OR
9/12 isoniazid (+pyridoxine)
OR
Rifapentine weekly for 3/12
Treatment of active TB
2/12 of ‘RIPE’ (+pyridoxine)
then
4/12 of rifampicin + isoniazid
Antibody target in ITP
GP IIb/IIIa complex
CHARTS Acronym for upper zone fibrosis
Coal worker's pneumocosis Hypersensitivity pneumonitis (AKA extrinsic allergic alveolitis) / histiocytosis Ank spond Radiation Tb Silicosis / sarcoidosis
OR: ‘everything you inhale except for ank. spond. and sarcoidosis’
Ventilation strategy for patients with ARDS
Low tidal volume (4-8ml/kg) with PEEP
Smouldering myeloma criteria
AKA ‘asymptomatic myeloma’
- Paraprotein >30
OR
Plasma cells >10% - AND no myeloma-relate end-organ impairment
MRI findings in CJD
Caudate and putamen T2 hyperintensity and diffusion restriction on DWI/ADC
Proven benefit(s) of pre-endoscopic PPI
Reduced endoscopic intervention (i.e. no difference in mortality, re-bleeding or surgery)
Home oxygen indications for COPD
PaO2 <55mHg (7.3 kPa)
OR
PaO2 <60mmHg (7.7 - 7.8 kPa) if cor pulmonale / right HF / erythrocytosis / pulmonary HTN
Group of patients that might particularly benefit from CABG (rather than PCI)
Diabetics
Treatment for BRAF V600E mutation in melanoma
BRAF inhibitor AND MEK inhibitor combination
e.g. Dabrafenib + Trametinib
Treatment for cerebral venous sinus thrombosis
Clexane + warfarin, then warfarin once INR therapeutic (even if small intracranial bleed)
NO evidence for DOACs
Skin complication of anti-TNF Rx
Psoriasis
MDR-TB definition
TB resistant to Rifampicin and Isoniazid
XDR-TB definition
MDR-TB + resistance of moxifloxacin and amikacin
5-FU-related chest pain mechanism
Coronary artery spasm
Usually associated with first infusion
Antibiotic inactivated by surfactant
Daptomycin (due to aggregating with phospholipids in surfactant)
Antibiotic with large volume of distribution, and so not useful in sepsis
Tigecycline
Hemibalism site of lesion
Contralateral sub-thalamic nucleus or basal ganglia
One interesting cause includes hyperglycaemia
Anti-epileptic that can worsen absence seizures
Carbamazepine
Anti-GAD Abs
- Found in:
- Results in (syndrome)
Breast, colorectal, SCLC
Stiff man syndrome (diffuse hypertonia)
Anti-Hu
- Found in:
- Results in:
SCLC, neuroblastoma
Limbic encephalitis, rapid peripheral neuropathy
Anti-Ma
- Found in:
- Results in:
Testicular cancer
Rhombencephalitis
Anti-Yo
- Found in:
- Results in:
Breast, ovarian
Cerebellar degeneration
Anti-Ri
- Found in:
- Results in:
Breast, SCLC
Ocular opsoclonus myoclonus, rhombencephalitis
Anti-amphiphysin
- Found in:
- Results in:
Breast
Stiff person syndrome
LGI1 Encephalitis
- What is it
- 2x key features
A subtype of anti-VGKC-mediated encephalitis
Rapid memory decline
Faciobrachial and dystonic seizures
Osteoprotegerin functions (2)
AKA Osteoclastogenesis Inhibitory Factor (OCIF)
Acts as decoy for RANK-L (thereby reducing stimulation of osteoclastic maturation)
Acts as decoy for ‘TRAIL’ (thereby inhibiting apoptosis of osteoclasts)
Hb-O2 curve: causes for RIGHT shift
E.g. in muscle:
- Increased temp
- Increased pCO2
- Lower pH (increased H+)
- Increased 2,3-BPG
Bohr Effect
Increased pCO2 / H+ make O2 bind Hb with less affinity (thereby increasing its delivery to metabolically-active tissue)
Components of HbA
2x alpha + 2x beta chains, i.e. normal adult Hb
Components of HbF
2x alpha + 2x gamma chain (foetal Hb)
What is HbS?
Sickle cell Hb - due to point mutation in beta chain
Mutated beta chains join with normal alpha chains to form HbS
If homozygous –> sickle cell anaemia
HbS has reduced solubility when deoxygenated → undergoes polymerisation → distorted shape → reduced flow/deformability + increased adhesion to endothelial cells
What is HbE?
Beta gene mutation causing structurally abnormal Hb
Weak union beta alpha/beta –> unstable Hb (behaves like beta-thal trait)
Implications if one parent has HbE and the other beta-thal
What is HbH?
Moderate-severe form of alpha-thal where only 1x functional alpha gene is present (i.e. -a / –)
HbH is made from beta chains (beta-4) that combine to each other
What is HbB?
Hb Barts
Hb made of 4x gamma chains
Seen in alpha-thal major (i.e. no functional alpha genes present)
Components of 4T score for HIT probability calculator
Thrombocytopaenia
Timing
Thrombosis
Other causes present
What is Gaucher Disease (1)
Most common manifestations (4)
Most common lysosomal storage disease; abnormal glycolipid build-up in macrophage lysosomes (‘lipid-laden macrophages’) due to deficiency in glucocerebrosidase enzyme.
Splenomegaly
Thrombocytopaenia
Neurological deficit
‘Flask’ appearance of long bones
Rx = enzyme replacement therapy OR substrate reduction therapy
Components of ‘Fried Frailty Tool’ (AKA Frailty Phenotype) (5)
Weight loss >5% Fatigue Reduced grip strength Reduced mobility speed Decreased weekly physical activity (based on energy expenditure)
What organism causes erythrasma?
Corynebacterium
pink/brown patches in groin/axillae
Interventions that improve COPD mortality (3)
Stop smoking Home O2 (if meets criteria) Lung reduction surgery in selected cases
True / False: Obesity increases BNP
False - along with standard HF Rx, obesity also decreases BNP
Gestational diabetes diagnosis thresholds for BSL:
- Fasting
- After 2h
> = 5.6
> =7.8
Muscarinic Receptors
G-protein coupled
M1 (Gq) - CNS
M2 (Gi) - Heart
M3 (Gq) - Other organs: gut, glands, eyes, blood vessels
Nicotinic receptors
Ligand-gated ion channels
N1 / Nm - NMJ
N2 / Nn - post-ganglionic cell body / adrenal gland
Th17 cytokines
IL-17
IL-22
(Small amount of IL-10)
What type of growth factor is produced by myxomas?
VEGF
Most common type of malignant primary cardiac tumour
Sarcomas
But metastatic cardiac tumours 20x more common
Example of ergot-derivative meds (2)
Mechanism
Key side-effects (2)
Bromocriptine, cabergoline
- Work as dopamine receptor agonists
Pulmonary / cardiac / retroperitoneal fibrosis
Impulse control disorders
In utero lithium exposure increases risk of the following cardiac abnormality:
Ebstein’s anomaly (low insertion of the tricuspid valve –> large RA, small RV)
See prominent TR and a-waves
Pathergy test:
- What is it?
- What condition is it found in?
Exaggerated skin injury after mild trauma
Behcet’s disease (also in pyoderma gangrenosum and Sweet syndrome)
What is the EMA test for?
Diagnosis of hereditary spherocytosis.
Test measures amount of fluorescence from a cell.
Lights criteria for exudative effusion
1 of:
Pleural:serum protein >0.5
Pleural:serum LDH >0.6
Pleural LDH >2/3 of serum LDH ULN
Haemorrhagic bullae are caused by what organism?
Vibrio vulnificus
Further info:
G-, seafood ingestion or contaminated wound, severe sepsis, particularly liver disease or haemochromatosis, tetracycline + 3rd gen cephalosporin
Key urine finding in ATN
‘Muddy-brown’ granular, epithelial cell casts and free renal tubular epithelial cells (that have been ‘shed’)
AML: cytogenetic changes with good prognosis (4, 1)
t(8;21) (which generates the RUNX1-RUNX1T1 fusion gene)
t(15;17) (APML)
inv(16)
NPM1 mutation
For these cases, can try cytaribine consolidation (rather than SCT)
AML: cytogenetic changes with poor prognosis (5)
-5, -7, del (5q), abnormal 3q, FLT3
PD-1 inhibitors
Pembrolizumab
Nivolumab
PD-1L inhibitors
Atezolizumab
Durvalumab
CTLA-4:
- Mechanism
- Examples of blockers
Preferentially binds co-stimulatory molecule CD80/86 (AKA B7) –> loss of T-cell activation
Ipilimumabc
MELD score components
Dialysis Creatinine Bilirubin INR Sodium
Child pugh components
Bilirubin Albumin INR Ascites Encephalopathy
Enterococcus endocarditis Rx (2)
Gent-sensitive / standard:
Amoxicillin 6/52 + gentamicin 2/52 (synergy)
Gent-resistance:
Amoxicillin + ceftriaxone (6/52 for both) (synergy)
- Amox covers PBP4 and 5
- Cef covers PBP2 and 3
Organisms that do not produce nitrites
Gram positives:
Enterococcus
Staph. saprophyticus
Riociguat
- Use
- Mechanism
Medical therapy of CTEPH (in rare cases where surgical intervention (thrombendarterectomy) is not done).
Guanalate cyclase agonist (which enhances the effects of NO binding)
What is erythromelalgia?
Intermittent red/hot extremities.
Associated with MDS
Conservative cooling measures and aspirin
Peritoneal dialysis-associated peritonitis management overview (5)
Most common organism: S. epidermidis
Either continuous or intermittent (at least 6h dwell) administration.
Empiric Rx = Gentamicin + Cefazolin
If vancomycin required, replace cefazolin with it
If suspected diverticulitis / intestinal perf, add metronidazole
If gentamicin contraindicated, use single-agent cefepime regimen
Duration 14-21 days
Spirometry: fixed obstruction flow-volume loop description
Plateaued inspiratory and expiratory phases
Spirometry: variable intrathoracic obstruction flow-volume loop description
Plateau of expiratory phase
Normal inspiratory phase
Spirometry: variable extrathoracic obstruction flow-volume loop description
Normal expiratory phase
Plateau of inspiratory phase
LADA one sentence description
Slowly progressive destruction of beta cells - gradual insulin deficiency (not as rapid as ‘traditional’ T1DM, but still a subtype of T1)
(NOTE: Starting insulin early may help to preserve beta cell function)
MODY one sentence description
Monogenetic cause of diabetes (with variable penetrance) due to genetic defect in beta cell function
Hepatitis B infection phases
- Immune tolerance
- High DNA, high HBe antigen - Immune clearance
- Falling DNA, +/- falling HBe antigen, rising AST - Immune control
- Anti-HBe +, low DNA, normal LFTs - Immune escape
- Rising DNA, rising LFTs, HBe still -ve
When to treat hep B: (2)
Liver injury and DNA > 20,000 (and +ve E antigen)
OR
DNA > 2,000 and negative HBe antigen (i.e. immune escape phase)
Contraindications for interferon therapy (4)
Thyroid disease
Psychosis
Child-Pugh B/C (can trigger decomp)
Autoimmune disease
Tenofovir complications (2,1)
Low BMD
Fanconi syndrome / renal impairment
(But safe in pregnancy)
Type of adenoma that secretes mucous and can result in diarrhoea with a rare ALKALOSIS
Villous adenoma
Cardiac action potential steps
0 (depol) - rapid Na influx 1 (notch) - K+ efflux 2 (plateau) - Ca++ influx, K+ efflux 3 (descent) - K+ efflux 4 (resting) - K+ influx (Na/K ATPase)
RANZCOG cutoffs for GDM after 2h OGTT
Fasting >5.1 - 6.9 (>7 = diabetes)
1h > 10
2h > 8.5 - 11 (>11.1 = diabetes)
(Different to NZ screening guide)
Note: Aus and WHO recommend one-step test with 75g OGTT (not 50g test as in NZ)
Osmolar gap formula
Osmolar gap = Osmolality (measured) – Osmolarity (calculated)
Normal <10
If high, implies presence of an abnormal solute present in significant amounts e.g. methanol, ethylene glycol
Bullous pemphigoid pathophysiology
IgG against hemidesmosomal proteins BP 180 and BP 230 (deep) –> eosinophil infiltrate –> dermal / epidermal splitting
Pemphigus vulgaris pathophysiology
IgG against desmoglein 1 & 3 –> loss of cell adhesion in epidermis (superficial) –> easily rupturing blisters
Bortezomib / carfilzomib mechanism / use
26s proteosome inhibitor (–> build-up of intracellular M-protein –> apoptosis)
Myeloma induction (along with lenalidomide and dexamethasone)
Daratumumab mechanism (and 1x laboratory complication)
mAb to CD38 on multiple myeloma cells (used in relapsed disease)
(Can cause pan-agglutination on antibody screen when looking for a cross-match, i.e. pan-reactive red cell antibody)
Chromosome translocation: follicular lymphoma / (some) DLBCL
t(14;18) –> BCL-2
BCL-2 inhibits apoptosis
Chromosome translocation: CML
t(9;22)
Chromosome translocation: Burkitt lymphoma
t(8;14) –> Myc
Disease with ‘starry sky’ appearance on node biopsy
Burkitt Lymphoma
AVRT - current directions and associated ECG appearance
Orthodromic - narrow complex
Antidromic - wide complex (due to LV being activated first)
SVT / IV adenosine special scenarios (3)
- Contraindicated in asthma
- Need higher dose if on theophylline
- Need lower dose if on dipyridamole
Typical vs atypical AVNRT
Typical: slow–>fast conduction, short R-P interval
‘Short and slow’
Opposite in atypical AVNRT
R-factor:
- Formula
- Interpretation
ALT / ULN : ALP / ULN
<2 = cholestatic --> US >5 = hepatocellular --> liver screen 2-5 = mixed --> biopsy
Effect of trimethoprim on potassium
Can increase K+ (usually in AIDS patients) due to inhibition of ENaC
Perhexiline prescribing considerations
7-10% of caucasians are slow metabolisers due to deficient CYP2D6 - check metabolite level 3/7 after starting; if no peak, change to 100mg per WEEK dosing.
Can also cause hypoglycaemia
Beta-blocker with additional effect of potentiating the vasodilatory effect of NO
Nebivolol
Beta-blockers that have low lipid solubility (don’t cause CNS effects)
Atenolol
Nadolol
Celiprolol
Sotalol
Drugs to avoid in WPW + AF (pre-excited AF)
AV node blockers e.g. CCBs, BBs, adenosine
One MET
4 METs
10 METs
Resting metabolic demands
Climbing 2x flights of stairs
Strenuous sports
Hallmark finding of ASD on exam:
Wide and FIXED splitting of S2
Mutation in familial pulmonary HTN
Bone morphogenetic protein receptor type 2 (BMPR2) (in the TGF-beta family)
(Also often found in 10% of ‘sporadic PAH’)
Role of hypocretin/orexin
A wakefulness promoting protein, deficient in narcolepsy. Coded by orexin gene.
FEV1 (volume) cut-off for lobectomy
> 1.5L usually used
Implication of blood in pleural fluid (in context of cencer)
Pleural invasion - hence also not curative via surgery
Mining exposure that increases TB risk
Silica (via impairment of macrophage function)
Main risk factors for chronic lung allograft dysfunction (2)
Acute cellular rejection
Lymphocytic bronchiolitis
These cause bronchiolitis obliterans syndrome
May be contributed to by silent aspiration
Idiopathic pulmonary fibrosis histology findings (1,3)
Pattern = usual interstitial pneumonitis (UIP)
Minimal inflammatory round cell infiltrate
Widening of alveolar septa
Fibrosis / fibroblastic foci
Bronchoalveolar lavage finding in pulmonary alveolar proteinosis (2)
Grossly turbid exudates
Periodic acid-Schiff (PAS)-positive material
(Disease due to abnormal accumulation of surfactant in alveoli and impaired GM-CSF function)
HRCT finding in pulmonary alveolar proteinosis
‘Crazy paving’
What does faecal immunochemical test bind to?
Globin part of Hb
More sensitive/specific than gFOBT
Doesn’t detect upper GI blood, but does react with lower GI bleed (commonly haemorrhoids or diverticular bleed)
‘Interface hepatitis’ or bridging necrosis on histology refers to:
Autoimmune hepatitis
(See plasma cells, rather than lymphocytes (as in chronic hep)).
(Can also see ‘piecemeal’ necrosis)
Immune-mediated destruction of intrahepatic bile ducts on histology refers to:
PBC
Deficiency in wet/dry beriberi
Thiamine (B1)
NAFLD weight loss effects:
3-5%
10%
Improves steatosis
Improves necro-inflammation
Plummer-Vinson syndrome
Iron deficiency and (keratinised) oesophageal webs
Periodic acid-Schiff-stained macrophages on small bowel biopsy indicates…
Whipple disease (Tropheryma whipplei)
Reason for low B12 but high folate in small intestinal bacterial overgrowth
Bacteria consume B12, but produce Folate
Foot process effacement is seen in…
Minimal change disease
Where in renal tract does ANP act to reduce sodium reabsorption?
Inner medullary collecting ducts
Which part of the tubule is most often involved in drug secretion?
Proximal tubule
Effect of FGF23 on phosphate
Lowers levels by inhibiting reabsorption in PCT
Hb Target in CKD
100-115
Higer levels have risk of:
- Stroke
- Thrombosis / VTE
- HTN
- Headache
- CHF
What causes dialysis-related amyloidosis?
Inability clear (or dialyse) beta-2 microglobulin which then deposits.
Most common manifestations of DRA are carpal tunnel syndrome and shoulder pain.
Also see cystic lesions on end of long bones.
Risk factors for aHUS (3)
Deficiency in factors H and I,
Low thrombomodulin
Activators of factors B and C3
Complication of gadolinium in CKD
Nephrogenic systemic fibrosis
(hence may need haemodialysis after MRI)
(See lots of CD-34 fibrocytes)
Post-transplant lymphoproliferative disorder:
- Main risk factor
- Most common transplant affected
- Management
EBV mismatch
Heart-lung or bowel (both 10-20%)
Reduce immunosuppression
Which glomerulonephritis is most likely to rapidly recur in a renal allograft?
Primary FSGS
Type of glomerulonephritis associated with highest VTE risk.
Idiopathic membranous nephropathy
What cell does PTH target in bone?
Osteoblast (which can then lead to osteoclast activation if constant PTH stimulation is present, but not intermittent PTH presence)
Effects of GLP-1 (4)
Stimulates insulin
Inhibits glucagon
Inhibits gastric emptying
Reduces appetite
Eyebrow-related sign in hypothyroidism
Loss of the outer 1/3 of the eyebrow
Does neurofibromatosis type 1 or type 2 typically present with vestibular schwannoma?
Type 2 (due to Merlin protein, AKA schwannomin), defect)
Gene / protein for Tay-Sachs disease
HEXA gene Hexosaminidase A (usually breaks down phospholipids / gangliosides)
Areas targeted by deep brain stimulation
Subthalamic nucleus
Internal segment of globus pallidus
Symptoms that respond to deep brain stimulation (4)
Levodopa-responsive Sx,
Tremor,
On-off fluctuations,
Dyskinesia
Alpha synucleinopathies (3)
Parkinson’s
Lewy body dementia
MSA
Management of myasthenic crisis
Plasmapheresis or IVIg
Regular bedside checks of ventilation
Oral prednisone
On nerve conduction study, prolonged/dispersed F-wave latency indicates…
Demyelinating disease
Examples of non-ergot dopamine agonists
Pramipexole, ropinorole
Risk of impulse control disorders
Neutrophil antigens that can cause false-positive pANCA result on indirect immunofluoroscopy (3)
Bactericidal permeability inhibitor (BPI)
Cathepsin G
Lactoferrin
‘Shared epitope’ predisposing to RA
Common amino acid motif: QKRAA
Usually found in HLA-DRB1, but sometimes in other alleles
Wide mouth diverticulae are pathognomonic for…
Scleroderma
Polyarteritis nodosa: what sized vessels are affected?
Medium (muscular) and small arteries (but no glomerulonephritis)
Polyarteritis nodosa: biopsy findings
Pan-mural necrosis, prediliction for bifurcations. Can lead to aneurysms/stenosis of arteries.
True/false: Polyarteritis nodosa affects the lungs?
False: affects all organ systems other than lungs
Suspect in systemic vasculitis, ANCA-negative, orchitis and abnormal renal angiography
Factors associated with a GOOD prognosis for RA (3)
Acute onset
Restriction to small number of large joints
Sero-negative
In patient with RA presenting with shooting pains / hyper-reflexia / hypertonia, consider…
Atlantoaxial subluxation (due to erosion/stretching of the transverse ligament)
(Often worsened by forward flexion of neck, which has anaesthetic implications)
Most common type of lymphoma associated with Sjogren’s
MALToma
True/False: Alopecia is included in diagnostic criteria for SLE.
False
Sunburn damage mechanisms:
- UVB
- UVA
UV B causes radiation to epidermis - the main cause of direct sunburn
- SPF is based on UV B blocking ability
UV A causes free radical generation (and can penetrate below the dermis)
Key features of fixed drug reaction (2)
Residual hyperpigmentation
Recurrence at previously-affected sites
Biopsy showing panniculitis and inflammation of septa in subcutaneous fat is suggestive of…
Erythema nodosum
Role of p53 / where it acts in cycle
Tumour suppressor via arrest of cell cycle at G1 (to allow DNA repair before progressing) and stimulation of apoptosis. I.e. stops entry into S-phase.
(Note, can have elevated levels of mutated p53 in cancer cells due to slow turnover)
True/False: Oestrogen receptor positivity is a favourable prognostic factor for breast cancer?
True
While HER2+ is negtive factor
Deficiency in nucleotide excision repair confers increased sensitivity to which type of chemo agents?
Platinum (due to reduced capacity to repair interstrand cross-links)
How does nucleotide excision repair work?
Removes helix-distorting adducts on DNA, e.g. those caused by UV or tobacco smoke
Main side effects of bevacizumab (2)
Hypertension (VEGF inhibitor)
(Can be managed with standard BP Rx)
Poor wound healing
When to give adjuvant chemo in breast cancer
Node positive
Or tumour >0.5cm
(Or other adverse prognostic features e.g. young age, negative hormone receptor status, high-grade tumour)
When to give RTx in breast cancer
All breast-conserving surgery
Or if tumour >5cm / node positive
Breast screening for women with BRCA mutation
Should start age 25-30, and may include MRI in addition to mammography
Cetuximab MoA
mAb to EGFR
Only works in wild-type KRAS, i.e. won’t work if there is a KRAS mutation
Erlotinib mechanism
TKI targeting EGFR (used in NSCLC and pancreatic cancer)
Risk group for EGFR-positive lung cancer (4 features)
Asian
Never smoker
Women
Adenocarcinoma (cf squamous)
(Also unlikely to be effective if there is a KRAS mutation)
Main side-effect of erlotinib
Acneiform rash (face/neck)
Correlation between severity of skin reaction and survival!
Sunitinib MoA
VEGF inhibitor (as well as PDGFR B, FLT-3 and c_KIT)
Used in RCC
Intracellular bacterial pathogens (5)
Listeria Mycobacterium Brucella Rickettsia Chlamydia
Name the only Gram-positive bacterium to produce endotoxins
Listeria monocytogenes
What cell does JV virus affect in the brain to cause PML?
Oligodendrocyte
What does CD34 staining correspond to?
Haematopoietic progenitor cells
Mechanism of Cholera toxin
Persistent activation of adenylate cyclase –> increase cAMP –> increased chloride secretion / decreased sodium absorption –> secretory diarrhoea
Aflatoxin associations
Mycotoxin produced by Aspergillus, associated with:
- HCC
- p53 mutation
PCR marker for dengue
NS1 protein
HAART drug most responsible for lipodystrophy
Zidovudine
Treatment for Strongyloides
Ivermectin
(Consider Dx in patients with enteric bacterial pathogen with pulmonary/GI system involvement, particularly if co-existent immunosuppression or HTLV-1 present)
How does G-CSF facilitate collection of stem cells for transplantation?
Activates neutrophils –> Release MMPs –> mobilises stem cells from marrow into periphery –> collected
How does thrombopoietin (TPO) regulate platelet levels?
Via effect on megakaryocytes (promotes survival and differentiation).
(Binds to TPO receptor in bone marrow, with higher free TPO levels being present if there are low peripheral platelets present to bind it)
Roles of vWF (2)
Binds F VIII, reducing breakdown (increases T1/2 5-fold)
Helps platelets bind to exposed collagen in blood vessels (via GP1b)
Which factor activates protrhombin?
Factor X (in complex with factor V) (the prothrombinase complex)
F X is inactivated by protein-Z protease
Role of prostacyclin
Inhibits platelet activation.
Also acts as vasodilator
Gram positive rods
Acinetobater Bacillus Clostridium Diphtheriae Listeria
Lesion of angular gyrus causes…
Gerstman syndrome
‘Onion skin’ fibrosis on liver biopsy refers to…
PSC
Periductal fibrosis, intra- and extra-hepatic ducts
What cell releases surfactant?
Type 2 pneumocytes (main component = DPPC)
What is strongest -ve predictor for CLL
Medication to use if this is present.
Del 17p
Use ibrutinib or venetoclax if this mutation (or p53 mutation) is present
What is the mechanism of fomepizole
Competitive inhibitor of alcohol dehydrogenase (used in ethylene glycol and methanol poisoning)
What is found in Brodman’s area 22?
Wernicke’s area
At what level of factor 8 deficiency does APTT become prolonged?
<45%
APTT mixing studies that initially correct but then prolong again after 1-2h incubation due to…
Weak autoantibodies to factor 8
CLL cell surface CD markers (4)
CD 5 (aberrant, normally on T cells) + CD 19 + CD20 + CD23
Hereditary spherocytosis; affected proteins (3)
Ankyrin
Spectrin
Band 3 red cell protein
(Usually AD inheritance)
Key lineage to distinguish between MDS and aplastic anaemia
Megakaryocytes
Condition that aplastic anaemia overlaps with nearly 50% of the time
PNH
Which type of cryoglobulinaemia is hyperviscosity syndrome associated with?
Type I cryoglobulinaemia
(Which is associated with Waldenstrom’s, myeloma and CLL)
(Sx usually at viscosity > 4.0 centipoise)
Main factors guiding dosage of iron-chelating therapy (3)
Presence of cardiac iron overload
Rate of transfusional iron
Body iron burden
(Best measured by periodic MRI and ferritin)
What is Evan syndrome
Autoimmune haemolytic anaemia with ITP seen in pregnancy
Gene mutation causing PNH
Phosphatidylinositol glycan class A (PIGA)
This is required for synthesis of GPI-anchored proteins including CD55 and CD59.
CD 55/59 are complement regulators. If deficient, excess complement-mediated intravascular haemolysis of affected cells occurs
Main cause of death in PNH
Thrombosis e.g. abdominal or cerebral veins
Main presentations of GvHD (3)
Rash, GI tract, liver
Cell marker for plasma cells
CD138
Risk factor for warfarin-induced skin necrosis
Protein C deficiency (due to exaggeration of initial hypercoagulable state)
Malignancies associated with EBV (3)
Nasal NK cell lymphoma
Burkitt’s lymphoma
T-cell lymphoma
Common complication / differential in Sickle Cell disease
Salmonella osteomyelitis (which may be masked / mimicked during vaso-occlusive crises)
Key features of Autoimmune polyendocrine syndrome type I
2 of 3 of:
- Mucocutaneous candidiasis
- Hypo-PTH
- Addison disease
Likely due to AIRE mutation
Predisposed to many other AI conditions
Conditions associated with thymoma (2)
Myasthenia gravis
Pure red cell aplasia (see anaemia / absent erythroblasts on BM but normal myeloid cells and megakaryocytes)
Chromosome for HLA
Ch 6
Which HLA encodes MHC-II
HLA-D
And expresses slightly longer peptides 15-25 amino acids in length
Which HLA encodes MHC-I
HLA-A, -B and -C
And expresses shorter peptides, 8-10 amino acids
Which TLR is activated by lipopolysaccharide (LPS)?
TLR4
LPS is the ‘prototypical’ PAMP
Difference between IgA1 and IgA2
Their heavy chains
Main location for:
- IgA1
- IgA2
Airways and serum
Colon
(Similar levels in small intestine)
NK cell surface markers
CD56 +
CD3 -
Mechanism of immunotherapy
Alters T-cell reactivity to antigen, causing reduction in cytokine release
(no longer thought to be due to reduction in IgE or from induction of ‘blocking IgG Abs
Macrophage-released cytokines
IL-1 (responsible for stimulating hypothalamus causing fever)
TNF
Basiliximab
- Use
- Target
Immune suppression induction
Targets CD25 (part of the IL-2 receptor)
(Can also be used during periods of acute rejection)
What does icatibant do?
Bradykinin antagonist, used in hereditary angioedema
True / False: tryptase is more useful in venom- or medication-related anaphylaxis that food-related anaphylaxis.
True
Type of tryptase found after mast cell degranulation
Beta-tryptase (the mature form)
Usual circulating tryptases are pro-alpha and pro-beta tryptase
Tests in hereditary angioedema (2)
Low C1inh level or function
Low C4 (due to persistent breakdown by C1 esterase, which isn’t being inhibited)
What measurement is used to calculate / compare a drug’s bioavailability?
Area under the curve
True / False: the dose of a drug affects its bioavailability.
False
Key pharmacodynamic property that guides efficacy of beta-lactams and lincosamides
Time the concentration is above the MIC (T > MIC)
I.e. time-dependent killing
Key pharmacodynamic property that guides efficacy of aminoglycosides and fluoroquinolones
Ratio of area under the curve over 24-h dosing (AUC0–24) to minimum inhibitory concentration (MIC);
AND the ratio of maximal concentration (Cmax) to MIC
I.e. concentration-dependent killing
Related to volume of distribution and clearance
Key pharmacodynamic property that guides efficacy of vancomycin (glycopeptides)
Total body exposure to the antibiotic (ratio of AUC0-24 to MIC)
(Also relevant to aminoglycosides)
Related to VoD and clearance
Is rifampicin a CYP inducer or inhibitor?
Inducer
E.g. reduces antiepileptic levels
Key CYP enzyme for warfarin (and examples of drugs that affect it)
CYP2C9 - which gets inhibited by:
- Omeprazole
- Metronidazole
- Cimetidine
- Amiodarone
How does ivabridine work
Slows heart rate via action on If channel in sinus node
What 2 parameters affect steady state drug concentration during an constant rate infusion?
Dose rate
Clearance
Caspofungin mechanism
Inhibits synthesis of fungal cell wall beta(1-3)-D-glucan component
(Low oral bioavailability, must be given IV)
Amphotericin B mechanism
Forms artificial pores in membranes by binding to ergosterol
‘Azole’ mechanisms
Inhibit CYP system, thereby stopping synthesis of ergosterol from lanosterol
Morphine receptors (4)
Mu - analgesia, euphoria, miosis, respiratory depression
Kappa - analgesia, miosis, respiratory depression, sedation
Sigma - dysphoria, hallucination, psychosis
Delta - Unclear
Mechanism of Tacrolimus
Binds FK506-binding protein –> inhibits calcineurin –> stops T-cell activation and IL-2 release
Mechanism of Cyclosporin
Activates cyclophilin –> inhibits calcineurin –> stops T-cell activation / IL-2 release
Which immunosuppressant causes cytokine-release syndrome
Anti-thymocyte globulin
Immunosuppressant that causes pneumonitis
Sirolimus (mTOR inhibitor, which stops cytokine signaling from activating the cell)
Also binds FK506 (like tacrolimus but doesn’t inhibit calcineurin).
Role of tRNA
Small RNA chain that transfers a specific amino acid to a growing polypeptide chain during translation.
What do microRNAs do?
Bind to complementary mRNA, reducing their expression or translation.
Which DNA nucleotide is the target for methylation / inactivation?
Cytosine
What is heteroplasmy?
The tendency for a mitochondrial mutation to be present in only a proportion of the cell’s mitochondrial genome copies.
Familial Adenomatous Polyposis:
- Gene
- Inheritance pattern
- When to start screening
- How frequently to sceen
APC (tumour suppressor)
Autosomal dominant
Sigmoidoscopy at age 12
Annually
Scenario with peripheral neuropathy, angiokeratomas, corneal whirls and murmur/hypertrophy is likely to refer to…
Fabry disease
(X-linked lysosomal storage disorder with accummulation of glycosphingolipid)
(Can also see renal failure and clots in the brain)
Diseases displaying anticipation (5)
Huntingtons Fragile X syndrome Spinocerebellar ataxia Myotonic dystrophy Friedreich ataxia
Huntingtons allele and number of copies causing disease
CAG
Normal <34 repeats
Variable penetrance 35-39
Disease > 40
Early onset >60
Acute intermittent porphyria:
- Inheritance pattern
- Enzyme affected
- Accummulated products
Autosomal dominant
Porphobilinogen deaminase
ALA and PBG
von Willebrand’s disease inheritance:
- Type 1
- Type 2
- Type 3
Autosomal dominant
Autosomal dominant
Autosomal recessive
Disease with co-dominant inheritance pattern
Alpha-1-anti-trypsin deficiency
Largest gene
Dystrophin
On x-chromosome
Location of magnesium absorption
Small intestine (via passive uptake)
Uptake is dependent on Mg levels, rather than intake
Role of magnesium in muscle contraction
Stimulates calcium reuptake by the sarcoplasmic reticulum
Site of Magnesium reabsorption
Thick ascending limb of loop of Henle
Mechanism of cocaine
Inhibits reuptake of:
- Dopamine (euphoria)
- Serotonin (confidence)
- Norepinephrine (energy)
Mechanism of ezetimibe
Inhibits transport of cholesterol across intestinal wall (increasing cellular LDL-R expression –> increased LDL uptake)
Mechanism of fibrates
Activates PPAR –> alter lipoprotein synthesis and catabolism
Gordon syndrome
- Mechanism
- Inheritance
- Key features (4)
- Treatment
WNK4 mutation –> increased sodium-chloride co-transporter expression
(‘opposite of Gittleman’)
Autosomal dominant
HTN, hyper-K+, low renin, NORMAL aldosterone
Thiazide diuretic
Examples of drugs that inhibit CYP2D6 (3)
Fluoxetine, paroxetine, bupropion
Drugs that rely on CYP2D6 for activation (2)
Codeine,
Tamoxifen
Main ECG finding in hypothermia
J-waves (AKA Osbourne waves)
Other findings include absent P-waves, PR interval prolongation, prolonged QRS, prolonged QT
Toxic metabolic product of methanol
Formaldehyde –> formic acid –> retinal / optic nerve damage
Toxic metabolic product of ethylene glycol
Glycolic acid –> acidosis / calcium crystals –> AKI
Which feature of Wernicke’s encephalopathy is first to resolve with thiamine administration?
Ocular palsies (within hours)
Smoking effect on clozapine / which CYP
Smoking induces CYP1A2 which increases clozapine clearance - may need up to double dose.
(Reverse applies with CYP1A2 inhibitors e.g. theophylline, cipro)
Which antiepileptic can cause encephalopathy secondary to high ammonia levels?
Valproate
How to calculate Variance (stats)
Standard deviation squared
Type I error
Null hypothesis is falsely rejected, i.e. a difference is found where it does not actually exist.
Alpha (p-value)
Type II error
Null hypothesis is falsely accepted, i.e. the study was unable to detect a difference that does actually exist
Beta (1 - power)
What statistical test to use to assess dependence between two variables (correlation)
Spearman’s rank correlation
Receptors affected by noradrenaline (3)
Alpha-1, alpha-2 and beta-1 (agonist for all) –> increased vasoconstriction and cardiac output
Cf. adrenaline which also has a beta-2 effect, thereby causing vasodilatin
Adverse effect via agonism of alpha 2 causing excessive vasoconstriction and organ hypoperfusion
Ventilation strategy for ARDS
Low tidal volume ventilation
+/- prone positioning
NOT high frequency oscillatory ventilation
Antidote for cyanide poisoning
Hydroxycobalamin
Normal pulmonary artery wedge pressure (PAWP)
6-15 mmHg
Estimates LA pressure (and LV end-diastolic pressure if no mitral disease)
Main rhythm complications during pulmonary artery catheters (2)
New RBBB
Ventricular or supraventricular tachycardia
What is degludec?
Ultra-long-acting form of insulin (T1/2 = 25h) - i.e. longer than glargine
(Due to multi-hexamer chains that slowly release monomers)
Key organ for AL amyloidosis
Kidney (disrupted GBM)
Also highest risk form of amyloid for heart disease
Key organ for AA amyloidosis
Kidney - nephrotic syndrome
Also GI tract and thyroid. Spares heart
Key organs for AF amyloidosis
Familial cardiomyopathy and familial neuropathy
Key protein = transthyretin
Tau-opathies (4)
PSP (no REM sleep disorder)
Corticobasal degeneration
Alzheimers
Fronto-temporal dementia
Joints affected in haemochromatosis arthritis
2nd and 3rd MCPs
Dopamine agonism ‘stages’ (as an ICU drug)
Low dose –> DA receptors –> improves renal flow
Medium –> beta-1 receptors –> increased cardiac output
High –> alpha-1 receptors –> vasoconstriction
Cause of ‘loss of y descent’ in JVP
Tamponade (equal pressures across chambers, so no rapid flow into RV)
(y descent = atrial emptying)
TAMponade = TAMpaX (i.e. absent y)
Causes of ‘rapid y descent’ in JVP (3)
Constrictive pericarditis
Restrictive cardiomyopathy
Severe TR
(Conditions that lead to rapid RV filling)
Chromosome / protein for Presenilin 1 (PSEN1)
Chromosome 14
Increased alpha-beta plaques - most common cause of early-onset familial AD
Chromosome for Presenilin 2
Ch 1
Which tumour marker is increased by smoking?
CEA
Receptor for substance P
Neurokinin 1 (antagonised by apripetant)
Why do patients with diastolic heart failure, e.g. HOCM, deteriorate rapidly in AF?
High reliance on atrial contraction during late diastole to fill the ventricle.
Chromosome for CFTR
Ch 7
Most common cystic fibrosis mutation
Delta F508
Phenotype II - CFTR is produced by abnormal trafficking of channel to Golgi
A-a gradient formula
A-a = PA02 - PaO2
PAO2 = FiO2 x (Patm - H2O) - (pCO2 / 0.8)
In normal setting, simplifies to 150 - 1.25(pCO2)
(H2O = 47mmHg)
True / False: H. pylori is a risk for GORD
False
HIV type in which to use Maraviroc
Dominant CCR5-tropic virus
Type of mutation most likely to disrupt production of a protein:
Nonsense mutation
Features of fascicular ventricular tachycardia (3)
QRS 100-140ms
RBBB pattern
Short RS interval
(Most common type of idiopathic VT from LV)
True / False: G-CSF reduces risk of febrile neutropaenia.
True
also some evidence that it increases the future risk of AML
Follow-up screening for normal colonoscopy:
FOBT 2 yearly or repeat scope at 10 years
Follow-up screening for low risk colonoscopy e.g. 1-2 fully-resected polyps
Colonoscopy at 5 years
Follow-up screening for high risk colonoscopy
Colonoscopy at 3 years
Follow-up screening if poor bowel prep or incomplete resection of polyps
Colonoscopy in 1 year
Anti-alcohol drug contraindicated in IHD
Disulfiram - alcohol + disulfiram reaction can cause cardiovascular instability
Cause of S4 heart sound
Active filling with atrial contraction into a stiff ventricle
Cause of S3 heart sound
Rapid flow deceleration / blood striking compliant LV / forceful mitral valve opening
Antibodies in neuromyelitis optica
Anti-AQP4-IgG4
Subcut morphine potency to oral morphine
Subcut is ~2.5x stronger than PO
Similar to IV
True / False: OSA is well-associated with restless leg syndrome
False
Best screening test for partner for beta-thalassaemia if considering pregnancy (and one person is known carrier)
Mean corpuscular volume <75
If low, then go for genetics
Mechanism of teriparatide
Chronically elevated PTH will deplete bone stores. However, intermittent exposure to PTH will activate osteoblasts more than osteoclasts. Thus, once-daily injections of teriparatide have a net effect of stimulating new bone formation leading to increased bone mineral density.
Malignancies with extra high VTE risk
Stomach
Pancreas
Suffix for DPP-4 inhibitors
‘-gliptin’
Prevent breakdown of incretins GLP-1 and GIP
Two most common causes of metabolic alkalosis
Gastric losses (vomiting or NG)
Diuretics
Narcolepsy HLA association
HLA-DQB1
Salicylate poisoning acid-base disturbances (2)
Early: respiratory alkalosis
Later: metabolic acidosis
(Often see mixed acid-base picture of these two)
Chromosome translocation: Mantle Cell Lymphoma / Myeloma
t(11;14) - good prognosis - cyclin D1 product
everything else bad in myeloma
Investigation to consider in patient with MS with urinary incontinence
Ultrasound - to assess for extent of bladder emptying
Basophilic stippling on blood film suggests (2)
Lead poisoning
Thalassaemia
Anti-GM1 antibodies associated with (2)
Multiple sclerosis
Multifocal motor neuropathy
Anti-GQ1b antibodies associated with…
Miller-Fisher syndrome
Cyclophosphamide / chlorambucil:
- Class
- Mechanism
Alkylating agents
DNA cross-linking
Doxorubicin, epirubicin:
- Class
- Mechanism
- Key side-eeffect
Anthracyclines
Intercalates DNA / Inhibits topoisomerase II –> no DNA/RNA synthesis
Dose-dependent cardiomyopathy
Paclitaxel, docitaxel:
- Class
- Mechanism
- Key side-effect
Taxanes
Overstabilises microtubules / no disaggregation (no mitosis)
Neuropathy, hair loss
Vincristine:
- Class
- Mechanism
- Key side-effect
Vinca alkaloid
Inhibits mitotic spindle formation / no aggregation (no mitosis)
Neuropathy, hair loss
Bleomycin:
- Class
- Mechanism
- Key side-effect
Peptide ‘antibiotic’
DNA strand breakage
Pneumonitis
Cisplatin, oxaliplatin:
- Class
- Mechanism
- Key side-effect
Platinum-based
DNA cross-linking
Neuropathy, hearing loss, nephrotoxic
5-FU, AZA, MTX:
- Class
- Mechanism
- Key side-effect
Anti-metabolites
Inhibits purine/pyrimidine synthesis
Hand-foot disease, mucositis
Ironotecan, etoposide:
- Class
- Mechanism
- Key side-effect
Topoisomerase 1 inhibitors
Topoisomerase normally rejoins DNA during synthesis)
D/V
Cetuximab; key side-effect
Acneiform rash
Lapatinib:
- Mechanism
- Use
Dual TKI (EGFR and HER2)
Breast cancer
Palbociclib, ribociclib:
- Mechanism
- Use
CDK4/6 inhibitors –> stops inactivation of tumour suppressor Rb –> reactivated Rb prevents progression of cell cycle past G1
HR+ breast cancer (along with aromatase inhibitors)
Trastuzumab-emtansine mechanism
Antibody-drug (DM1) conjugate - used in breast cancer
Olaparib:
- Mechanism
- Use
PARP inhibitor –> prevents DNA base excision repair –> cell accumulates damage / double-stranded breaks (due to deficient BRCA repair) –> apoptosis
= concept of ‘synthetic lethality’
BRCA-mutated ovarian/peritoneal cancers
Average COVID incubation period
4-5 days
Key CT chest change in COVID (2)
Ground glass opacification (86%) +/- mixed consolidation (58%)
Peripheral or lower distribution typically
COVID virus type
Positive sense, single-stranded RNA virus
Host receptor for COVID entry
ACE2 (which binds to ‘spike’ protein of virus)
same as for other SARS-causing viruses
COVID ventilation strategy
Low tidal volume (<6ml/kg) with PEEP.
If this fails, then try prone ventilation.
Medications to consider in COVID patients:
- If severe / not on O2
- If severe and on O2
- ICU patients
Remdesivir (RNA polymerase inhibitor)
Low dose dexamethasone + remdesivir
Dex, no remdesivir, +/- IL-6 inhibitors
Axonal pathology effect on NCS amplitude
Lower amplitude - i.e. fewer axons excited with a given stimulus
What sort of disease causes slowed velocity / increased latency on NCS?
Demyelinating or compression e.g. carpal tunnel
What is ‘temporal dispersion’ on NCS
When the CMAP becomes ‘spread out’ due to patchy demyelination and signals arriving at different times to recording electrode
Conditions that cause a conduction block on NCS (2)
Multifocal motor neuropathy
Severe demyelination
What causes fibrillation / ‘positive sharp waves’ on EMG?
Denervation of muscle fibre (which then increases expression of ACh-R and becomes sensitive to ‘background’ ACh levels)
What causes ‘dive bomber’ sound on EMG?
Myotonia
EMG changes in neurogenic pathology:
- Amplitude
- Recruitment
Increased (one nerve now supplying many muscle fibres)
Decreased
EMG changes in myopathic pathology:
- Amplitude
- Recruitment
Reduced amplitude
Increased / early recruitment - trying to get more muscle fibres involved
What does burst suppression on EEG indicate?
Induced coma or post-cardiac arrest.
Normal frequency of brain waves
8-12 Hz (alpha waves)
Gene implicated in juvenile myoclonic epilepsy
ICK (found in 7%)
Juvenile myoclonic epilepsy:
- EEG findings
- Medications
4-6 Hz spike or spike-wave discharges
Valproate or lamotrigine
Mechanism of levetiracetam
SV2A modulator
Seizure type associated with post-ictal psychosis
Focal impaired awareness seizures , temporal lobe
see onset 1-3 days after cluster of seizures
3Hz spike-wave discharges associated with…
Childhood/juvenile absence epilepsies
What HLA allele to test for before starting carbamazepine?
HLA-B15:02
Mutation in what allele has increased risk for statin-induced myopathy?
OATP1B1 (reduced hepatic clearance)
What HLA allele increases SJS risk in people taking allopurinol?
HLA-58:01
Lamotrigine mechanism
Glutamate antagonist
Key features for type I (distal) RTA (3)
Urine pH >5.5 (despite acidosis)
Hypocitraturia
Hypercalciuria / stones
Common causes of type II RTA / Fanconi syndrome (3)
Monoclonal light chain disease
Medications (tenofovir, acetazolamide, topiramte)
Sjogren’s syndrome
What is Kussmaul’s sign / what does it demonstrate?
Absence of inspiratory decline in JVP
Seen in constrictive pericarditis or restrictive cardiomyopathy, RV infarction, severe RV dysfunction e.g. large PE
What disease shows LV-RV interdependence (i.e. SAI > 1.1)
Constrictive pericarditis
increase in RV pressure with inspiration, decreased LV pressure
What happens to LV pressure during inspiration in restrictive cardiomyopathy?
No change
But RV pressure decreases
What disease is associated with a pericardial knock / mechanism.
Constrictive pericarditis (stiff pericardium results in sudden arrest of ventricular filling)
(Corresponds with y-descent)
What does a Qp:Qs ratio of >1.5 indicate?
The presence of a shunt between pulmonary and systemic circulations (ratio should be 1.0)
Calculating RV pressure
which ~ mean pulmonary artery pressure
Pressure (RV) = Pressure (RV-RA) + Pressure (RA)
(RA pressure measured by looking at IVC)
(In absence of RVOT obstruction, RV pressure = pulmonary artery systolic pressure
Calculating pulmonary vascular resistance
(mPAP - LA) / Qp
(Where LA is measured by the PCWP)
(Where Qp ~ Cardiac output)
(Where Qp ~ Qs if no intracardiac shunt)
> 3 woods units = pulmonary HTN
Calculating systemic vascular resistance
(Ao - RA) / Qs
I.e. change in pressure / flow.
Where: Q ~ CO
Ao ~ MAP
Procedure of choice for rheumatic mitral stenosis
Percutaneous transvenous mitral commissurotomy (PTMC) AKA percutaneous mitral balloon valvotomy
Management for methaemoglobinaemia
- Acquired
- Congenital
Methylene blue
Ascorbic acid
Reversible complications of haemochromatosis (2)
Cardiomyopathy
Skin bronzing
Irreversible complications of haemochromatosis
Arthritis
Diabetes
Hypogonadism
Cirrhosis
‘Classic’ salmonella features (3)
Relative bradycardia
Pulse-temperature dissociation
Rose spots on trunk
Typhoid fever Rx (3)
Most: azithromycin OR ciprofloxacin OR ceftriaxone
If acquired in Pakistan –> carbapenem
Erradication with 4/52 cipro
Most sensitive test for diagnosing typhoid fever
Bone marrow culture (~90%)
Role of FGF23/Klotho and 2x mechanisms for this.
Lowers phosphate via 2x mechanisms:
Promotes phosphate excretion at PCT
Inhibits alpha-1-hydroxylase –> stops vit D activation –> stops phosphate absorption
Key tumours of MEN1
Parathyroid
(anterior) Pituitary (esp. prolactinoma)
Pancreas (or other GI cancers e.g. Z.E. syndrome)
MEN2a vs MEN2b
Both have medullary thyroid cancer
Both have phaeochromocytoma
Men2a also has hyper-PTH
Men2b has more neuromas/gangliomas/more aggressive
Calcitonin can be used to monitor for what type of cancer recurrence?
Thyroid medullary carcinoma
Thyroglobulin can be used to monitor for what type of cancer recurrence?
Thyroid papillary or follicular.
Note: need to also measure anti-thyroglobulin at the same time.
CT brain signs of cerebral venous thrombosis (3)
Dense triangle sign
Empty delta sign
Cord sign
Most common genes in familial motor neuron disease (2)
C9ORF72 - 40%
SOD1 - 15%
Riluzole mechanism
Inhibits glutamate release / promotes reuptake –> reduced stimulation of glutamate receptors.
Frequency of immunoglobulins in blood (most common to least common)
IgG IgA IgM IgD IgE
Free vs total PSA in prostate cancer
In prostate cancer, there is a LOWER proportion of free PSA to total PSA
(Larger fraction of PSA can escape proteolysis by ‘leaking out’ of malignant cells, thereby not forming ‘free PSA’)
Types of von Willebrand’s disease (3)
Type 1 - deficient production, but existing factors are normal (most responsive to DDAVP)
Type 2 - non-functioning vWF
Type 3 - deficiency in vWF
What blood group is associated with low vWF levels?
Group O (30% lower)
Haemophilia A severity levels
Based on factor activity levels:
Severe - <1% - only see spontaneous bleeds in this category
Moderate 1 - 5%
Mild 5 - <40%
Alpha-1-anti-trypsin - concept of ‘gain of function’ vs ‘loss of function’ toxicity
Loss - lung pathology due to loss of protection against elastase
Gain - liver pathology due to accumulation in liver cells of unsecreted AAT protein
Calculating RV systolic pressure using Bernoulli equation
RV pressure = 4(TR peak velocity)squared + RA pressure
Management of pulmonary oedema in pregnancy due to mitral stenosis
Beta-blocker
Usually a high flow state, so by slowing HR –> improves (reduces) pressure gradient across valve
‘Hockey stick’ deformity on ECHO indicates
Mitral stenosis
Formula for valve area
A1 x V1 = A2 x V2
What is low flow / low gradient stenosis?
In conditions with low flow, e.g. cardiomyopathy, severe hypertrophy, the ventricle can’t generate enough pressure to open valve.
Makes surface area look small (‘severe’) but is actually only moderate disease.
Investigate with dobutamine test which should increase contractility and increase flow/gradient. If true ‘anatomic’ stenosis, then valve area shouldn’t change.
What is dimensionless index?
Ratio of LV outflow (V1) : velocity across valve (V2)
Ratio <0.25 = area <1/4 normal, i.e. severe
‘Fish mouth’ valve is suggestive of…
Severe mitral stenosis in rheumatic heart disease (fusion of commisures)
‘Beads on a string’ on MRCP/ERCP suggests…
PSC
‘Sausage-shaped’ pancreas on CT suggests…
Autoimmune pancreatitis (a/w IgG4 disease)
Further supported by absence of surrounding inflammation or peripancreatic fluid
Mechanism of mepolizumab
anti-IL-5
Conditions in which pregnancy is ‘contraindicated’ / WHO risk group IV (7)
Pulmonary arterial hypertension LVEF <30% Previous peripartum cardiomyopathy with ANY residual dysfunction Severe MS or AS Marfans with aorta >45mm Aorta >50mm if bicuspid valve Native severe coarctation
True / False: Teriparetide reduces hip fractures
False. But it does reduce vertebral and other non-vertebral fractures
Mutation causing x-linked agammaglobulinaemia
Defect in Bruton’s tyrosine kinase
Frequency of colonoscopy in patients with PSC and UC
Annually
True / False: High dose vitamin D supplementation can increase falls.
True
bDMARDs that work in ank spond (2)
Anti-TNF
Anti-IL-17 (Secukinumab)
Mechanism of hydroxyurea in sickle cell disease
Increases HbF production
Listeria meningitis treatment option if patient is penicillin-allergic
IV cotrimoxazole
Changes in types of valve disease in rheumatic fever with time
Initial MR is most common, then MS becomes more common in 30’s due to fibrosis, then multivalvular in 50’s.
Medical options for pituitary Cushing’s disease (2)
Cabergoline
Pasireotide
Medical options for adrenal Cushing’s syndrome (4)
Ketoconazole
Metyrapone (inhibits 11-hydroxylase)
Etomidate (emergency)
Mitotane (irreversible)
Australia pneumonia recommendations:
- Mild
- Moderate
- Severe
Amoxicillin OR doxy
Benpen + doxy/clarithromycin
Ceftri + azithromycin
Which anti-fungal typically has therapeutic drug monitoring applied during use?
Voriconazole
What is released by D cells?
Somatostatin
What is released by I cells?
Cholecystokinin
B and T-cell deficient disorders (‘WASH’)
Wiskott-Aldrich syndrome
Ataxic telangiectasia
SCID
Hyper IgM syndromes
What are ‘eosinophilic intracytoplasmic inclusions’ more commonly known as?
Lewy Bodies (alpha synucleinopathy)
What is the mechanism(s) of golimumab / certolizumab?
Anti-TNFa
Osteophyte location in DISH spine x-ray
Anterior spine
Hormone profile associated with BRCA1
Triple negative
Higher a/w ovarian cancer
Hormone profile associated with BRCA2
HR+ (and PALB2 gene)
Higher a/w luminal / male breast cancer
Causes of raised DLCO (5)
Asthma Pumonary haemorrhage L-to-R shunts Polycythaemia Hyperkinetic states e.g. exercise
Causes of reduced DLCO (6)
'FAPPLE': Fibrosis Anaemia Pneumonia PE Low cardiac output Emphysema
Raised KCO with normal/reduced DLCO (3)
Pneumonectomy / lobectomy
Scoliosis / kyphosis/ankylosis
Neuromuscular weakness
Causes for false-positive VDRL / RPR (Cardiolipin tests)
SLE, TB, Malaria, HIV, Leprosy, anti-phospholipid syndrome, pregnancy
‘SomeTimes Mistakes Happen in LAParoscopy’
Organism that is a contraindication for CF patients to get lung transplant.
Burkholderia cepacia - cepacia syndrome
Which glomerulonephritis is associated with malignancies?
Membranous
What disease is suggested by ‘interface hepatitis’ on histology
Autoimmune hepatitis
See piecemeal necrosis / bridging necrosis in severe disease
Main cell types seen on liver biopsy for:
- Autoimmune hepatitis
- Chronic hep C
- Alcoholic hepatitis
Plasma cells
Lymphocytes
Neutrophils
What trinucleotide repeat is seen in myotonic dystrophy
CTG
Treatment regimens:
- TB
- MAC
‘RIPE’
‘RiCE’ - rifampicin, clarithromycin, ethambutol
‘Stork leg’ is a sign/complication of what disease?
Charcot-Marie-Tooth disease
most common inherited peripheral neuropathy, predominantly motor Sx
Spinal Muscular Atrophy inheritance pattern
Autosomal recessive
Only valve that (normally) is bicuspid
Mitral
Most common mutation causing resistance to EGFR tyrosine kinase inhibitors
T790M
Causes of cyanotic heart disease (5)
"5 T's" Truncus arteriosus Tricuspid atresia Tetralogy of Fallot Total anomalous pulmonary vascular return Transposition of great arteries
(Other non-cyanotic conditions only cause cyanosis once the shunt reverses with Eisenmenger’s)
If lamivudine resistance develops, which subsequent antiviral has low long-term resistance rates?
Tenofovir
While entecavir has up to 50% resistance by 5 years
CD surface marker for monocytes/macrophages
CD14
True/False: Primary spontaneous PTX primarily occurs during exercise.
False
‘Storiform’ pattern on biopsy is suggestive of what disease?
IgG4-related disease
Inheritance pattern for fragile x syndrome
X-linked dominant
Aortic stenosis: order of clinical findings by prognosis (best to worst) (3)
Angina - 5 year survival
Syncope - 3 year survival
Heart failure - 2 year survival
What is platypnoea-orthodeoxia and a common cause of it?
Oxygenation better when lying flat
Hepatopulmonary syndrome
Effect/Outcome of:
- Single nucleotide deletion on reading frame
- Substitution of 1st or 2nd nucleotide in a codon
- Substitution of 3rd nucleotide in a codon
Frameshift mutation
Will change 1x amino acid
No change to amino acid - AKA degeneracy
Alzheimer’s CSF levels, what happens to:
- A-beta42
- Tau
Decreased
Increased
True / False: beta-lactams have high PO bioavailability?
False
Therapy for Cryptococcus neoformans or Cryptococcus gatii
Amphotericin B + Flucytosine
Gatii is found in Australia and affects immunocompetent hosts
Direction of eye movement by:
- Superior oblique
- Inferior oblique
SO4 - ‘SIN’ - trochlear nerve
- Superior oblique intorts (i.e. down and in)
Inferior oblique normally goes up and in (hence ‘3 strikes (CN3) and you’re down and out’)
Cells that make myelin:
- In the CNS
- In the PNS
Oligodendrocytes
Schwann cells
Spasticity vs rigidity (in terms of velocity)
Spasticity is velocity-dependent
Rigidity is tense throughout entire range of passive movement
Mechanism of p-glycoprotein pump
Acts as efflux pump, reducing the absorption of drugs across the intestinal wall, increasing excretion into bile, increasing renal secretion, preventing entry into CSF.
True / false: in type 1 respiratory failure, INITIAL treatment with high flow oxygen has lower mortality than NIV
True
And associated with lower intubation rates, especially in ARDS
What type of nodule is most likely to be malignant: solid vs part-solid vs ground glass nodule?
Part-solid
Distinguishing features of type 2 narcolepsy vs type 1 (2)
Type 2 narcolepsy:
- No cataplexy
- High CSF hypocretin/orexin levels
Main organ NOT involved in scleroderma
Brain
Essentially every other organ system affected, particularly skin, lung and GI tract
On liver CT with contrast, what does a ‘double target’ sign or ‘cluster sign’ refer to?
Liver abscess
BRCA-associated cancers (4)
'BOPP': Breast Ovary Pancreas Prostate
Which myositis antibody has the strongest association with malignancy?
Anti-TIF1y (AKA anti-p155)
True / False: acromegaly causes hypercalcaemia
True
Ustekinumab mechanism
Anti-IL-12 / IL-23
Vedolizumab mechanism / use
Anti alpha-4-beta-7 integrin
Gut-specific mAB used in moderate-severe UC. Safer in older patients at increased risk of infection or malignancy.
True / false: the following molecular profile has a good risk profile in AML?
NPM1 mutated / FLT3 wild-type
True
I.e. a mutation in FLT3 has adverse prognostic implication
In pregnancy, how is the minute ventilation increased?
Predominantly through an increased tidal volume
“Florid duct lesions” refers to…
PBC (granulomatous process)
Degeneration of interlobular and segmental bile ducts –> ‘ductopenia’
Agents that REDUCE the effect of warfarin (6)
'CRASHA': Cholestyramine Rifampicin Anti-epileptics St John's wort High vit K foods Azathioprine
For the exam, unless in this list, assume that it otherwise increases anticoagulation.
How to remove macroprolactin from blood assay
Pretreat with polyethylene glycol
aFP and b-hCG is elevated in which category of testicular germ cell tumours?
Non-seminomatous germ cell tumours
which is also more likely to present as metastatic disease compared to seminomas
Distinguishing between TSH-producing adenoma vs resistance to thyroid hormone as causes of secondary hyperthyroidism: which of the two entities will have a positive response to TRH stimulation?
Resistance to thyroid hormone syndrome
Which will also usually not have too high of a TSH level
Class of antivirals not recommended in decompensated liver disease (CP B or C)
Protease inhibitors
E.g. marivet
POEMS procedure, for achalasia, is associated with what adverse effect (compared to traditional myotomy)?
Higher rates of GORD/oesophagitis
Source of faecal calprotectin
Phagocytes (neutrophils and monocytes, calcium and zinc-binding protein)
(While faecal lactoferrin tests for leucocytes)
Which cells release Ghrelin?
P/D1 cells (most abundantly found in the gastric fundus)
Commonest type of incontinence in older people
Urge incontinence (due to detrusor muscle overactivity)
True / False: smoking is a significant risk factor for haemorrhagic stroke?
False
‘Smooth, diffuse meningeal thickening’ on MRI is suggestive of what disease?
POEMS Syndrome
Which component of the ‘metabolic’ syndrome is least associated with development of neuropathy?
Hypertension
True / False: MRI findings in idiopathic intracranial hypertension are predictive of risk of long-term vision loss.
False.
Key predictors of adverse outcome:
- High grade papilloedema
- Vision loss at presentation
- Transient visual obscurations prior to presentation
True / False: Transient global amnesia can have small findings on diffusion-weighted imaging.
True - usually seen after 12h
Reduced CD157 / FLAER binding on flow cytometry is suggestive of which disease?
PNH
When to add midostaurin in AML
If FLT3 mutation present (a membrane-bound tyrosine kinase that gets inhibited by midostaurin)
Consolidation medication in AML if good prognostic features present.
Cytarabine
If poor prognosis, consider allogeneic BMT
Ibrutinib:
- Mechanism
- Main side-effect
Bruton TK inhibitor - used in CLL, esp with del17p
Bruising / bleeding
Key side effects of venetoclax (2)
High risk of tumour lysis syndrome
Neutropaenia - common to use GCSF
Components of Tetralogy of Fallot
'PROV': Pulmonary stenosis RV hypertrophy Over-riding aorta VSD
Cause of large V waves on JVP
Tricuspid regurgitation
Common ECG change with TAVI
New LBBB seen in 20% due to proximity of valve to bundle of His - 40% resolve spontaneously
Chemo agents that cause lots of nausea
Platinum agents
Doxorubicin
Alkylating agents
Which territory MI has biggest risk for LV thrombus formation?
Anterior, especially if LV <30% or apical akinesis seen.
Rx = warfarin, NOT DOAC
2x main complications of catheter ablation treatment for AF
Atrio-oesophageal fistula (chest pain, fever, neuro from septic emboli)
- Posterior wall of LA is very close to oesophagus
Pulmonary vein stenosis
POTS diagnostic criteria
HR rising >30 from baseline on standing/tilt, or rising to >120bpm (without significant change in BP)
True / false: food allergies can be effectively managed by desensitisation immunotherapy.
False
But very effective for stinging/biting insects
Agents which reduce vertebral but not hip fracture (3)
Teriparetide
SERMs
Calcitonin
(While bisphosphonates, denosumab and oestrogen/progesterone reduces both classes)
What is efficacy vs effectiveness for a drug?
Efficacy = drug effect in ideal circumstances e.g. trial
Effectiveness = how well drug performs in real world
Which enzyme is affected by Lumacaftor/Ivacaftor
Massive induction of CYP3A4 - cannot give azoles
BODE Index:
- What is it?
- Components (‘BODE’)
Scale for predicting COPD survival / hospitalisation.
BMI
Obstruction (FEV1)
Dyspnoea (mMRC scale)
Exercise capacity (6MWT)
Between PKD1 and PKD2, which has worse prognosis for progressive renal disease?
PKD1 (associated with truncating mutations)
Lupus nephritis:
- Which classes to treat
- Induction regimen
Class III, IV +/- V
Steroids, MMF or cyclophosphamide
(reassess at 6 months)
True / False: In CKD, the goal for PTH is to have it in normal range.
False - goal is to have it less than 2-9x ULN
If it is normal, there is a high risk of adynamic bone disease
Side effects:
- Tenofovir disoproxil fumarate
- Tenofovir alafenamide
Renal impairment / Fanconi’s + lower BMD
Weight gain
Key finding of MERINO trial
In ESBL sepsis (E. coli or Klebsiella resistant to ceftriaxone), carbapenems had better outcomes than PipTaz
How to distinguish between ‘probable’ and ‘possible’ CVID
Both have reduced IgG and reduced vaccine response.
Possible –> normal IgA/IgM
Probable –> low IgA/IgM
Drug that increases mucormycosis infection risk
Deferoxamine
See ‘reverse halo’ sign on CT - ground glass change surrounded by wall of necrosis
True / False: Mucormycosis will not have positive galactomannan or 1,3-beta-glucan tests
True (need Dx via culture or histopathology)
Which cytokines are affected in MSMD (Mendelian Susceptibility to Mycobacterial Diseases)
IFNy and IL-12 –> no Th1 response –> intracellular infections
Prototypic event = lymphadenitis / systemic infection after BCG vaccine
Key findings of TULIP2 trial (re: SLE)
Treatment with Anifrolumab (anti-IL-1-R) associated with better composite outcome at 52 weeks than placebo
(And higher rates of herpes zoster)
Key findings of PLEXIVAS trial (re: ANCA-associated vasculitis) (2)
Plasma exchange did NOT reduce death or ESRF.
Low-dose steroids was non-inferior to standard dose (and had fewer infections).
What disease is anti-NT5C1a antibodies associated with?
Inclusion body myositis
What disease and complication is anti-MDA5 antibody associated with?
Dermatomyositis complicated by interstitial lung disease
What is the most common myositis-associated antibody?
Anti-Jo-1
a subtype of aminoacyl-transfer RNA (tRNA) synthetase antibodies
What disease is anti-Mi-2 antibodies associated with?
Dermatomyositis
May also indicate group at low risk of malignancy
Bronchoprovocation testing: what is the difference between methacholine and mannitol?
Methacholine = ‘direct’ stimulus, more sensitive for pick-up asthma
Mannitol = ‘indirect’ stimulus, more specific. Also better association with exercise.
What will excess Biotin levels do to troponin or TSH results?
False decrease (by occupying streptavidin binding sites instead of the anti-TSH Ab)
Type 1 Amiodarone Induced Thyrotoxicosis:
Mechanism
Treatment
Excessive thyroid hormone synthesis due to excess iodine substrate (Jod-Basedow effect)
Carbimazole, radio-ioidine, surgery
Type 2 Amiodarone Induced Thyrotoxicosis:
Mechanism
Treatment
Direct toxic effect on follicular cells (destructive thyroiditis - Type 2 AIT) → excess release of preformed T4/3
Steroids
What is the Wolff-Chaikoff effect?
Due to excess iodine load, there is inhibition of thyroid hormone synthesis
(People with underlying thyroid disease may not be able to overcome this)
Mechanisms of amiodarone-induced hypothyroidism (2)
Reduced conversion of T4 → T3
Wolff-Chaikoff effect
Angelman syndrome genetic pathophysiology
Maternal UBE3A (ch 15) gene is mutated while the paternal copy is imprinted
(Or from uniparental disomy)
Prader-Willi syndrome genetic pathophysiology
Deletion of paternal gene cluster on Ch 15 while maternal copies are imprinted
What cutaneous side-effect is seen with EGFR inhibitors? (And name some examples of drugs)
Acneiform rash
E.g. erlotinib, gefitinib, cetuximab
What is Osimertinib used for?
EGFR+ positive lung adenocarcinoma if progression on erlotinib or gefitinib demonstrated AND T790M mutation present
Drugs to use for ALK-positive lung adenocarcinoma (2)
Alectinib (first line) or crizotinib
What is the most common cause of secondary IgA nephropathy?
Alcoholic cirrhosis
True / False: there is no data demonstrating a benefit for statin therapy in CKD patients on dialysis.
True (except possibly in subgroups with very high LDL)
What cell is CTLA-4 on?
What does CTLA-4 bind to?
T cells (constitutively active on Tregs, induced on Th) B7 (CD80/86) - binds with higher affinity than CD28, thereby outcompeting it → inhibition
What is CD28?
Which cell expresses it, what does it bind to?
CD28 = co-stimulatory molecule on T cells
Binds to B7 (CD80/86)
True / false: the benefit of SGLT-2i’s in heart failure death/hospitalisation is only seen in patients with diabetes.
False
EMPEROR-reduced trial
Bortezomib:
Mechanism
Key side effect
26S Proteasome inhibitor → build up of cellular materials → apoptosis (used in multiple myeloma)
Painful peripheral neuropathy (30%)
Marfan’s inheritance pattern
Autosomal dominant (FBN1 gene)
TGFBR1 / TGFBR2 mutations are associated with which condition?
Loey-Dietz syndrome
What does secukinumab target?
Indication
IL-17
Associated with WORSE rates of IBD and no effect in RA - only used in psoriatic arthritis
Fracture risk cut-offs for starting osteoporosis treatment according to Aus guidelines:
Hip fracture risk
Any fracture
If 10 year risk for hip fracture is >3%, or risk for any fracture >20% → start anti-osteoporosis medication
Which BRCA has the greatest increased risk of male breast cancer?
BRCA2
Which BRCA has the greatest increased risk of ovarian cancer?
BRCA1
Gain of function / loss of function of SCN5A gene causes which syndromes respectively?
Gain - long QT syndrome
Loss - Brugada syndrome
What type of seizure are anti-LGI-1 antibodies associated with (autoimmune encephalitis Abs)
Facio-brachial dystonic seizures (looks like face / shoulder / arm myoclonus)
True / false: female carriers of muscular dystrophy mutations can have muscle weakness.
True - often mild/moderate.
Most common cause of primary nephrotic syndrome in adults?
Membranous nephropathy
What is the best technique for measuring core temperature (hierarchy)?
Central venous temp > oesophageal > bladder > rectal > tympanic
Best drug to manage depression/hallucination in Alzheimer’s
Citalopram
Key ECG lead in RV ischaemia
V4R
Empiric Rx for native valve endocarditis (3)
Benzylpenicillin + Flucloxacillin + Gentamicin
If prosthetic valve, replace benpen with vancomycin
Treatment for cytokine release syndrome
Tocilizumab
Diagnosis of Ross River Virus (3x modalities)
Haemagglutinin inhibition (HI) antibody test
- 4-fold rise = diagnostic
- titre >1:1280 = recent infection
ELISA
Virus-specific IgM (persist for months) - titres can reflect acute infection
What lymphoma is associated with ‘pan B cell markers’?
Diffuse Large B-cell Lymphoma
CD19 + CD20 + CD22 + CD79a
Rx with ABC, worse outcomes with R-CHOP
Components of R-CHOP
Rituximab Cyclophosphamide Doxorubicin Vincristine Prednisone
Mechanism of Brentuximab (and uses (2))
Anti-CD30 mAb coupled to a cytotoxic agent
Used in relapsed DLBCL and Hodgkin lymphoma (i.e. CD30+ conditions)
Nintedanib:
- Key side-effects (2)
- Mechanism
Diarrhoea
Deranged LFTs
(Multi-tyrosine kinase inhibitor, including inhibition of fibrogenic growth factors)
Pirfenidone:
- Key side-effects (2)
- Mechanism
Photosensitivity
Nausea
(Inhibitor of TGF-beta –> anti-fibrotic effects)
Myeloma therapy:
- Induction agents (3)
- Maintenance after autologous stem cell transplant (1)
Bortezomib + lenalidomie + dexamethasone
(Then autologous stem cell transplant after melphalan conditioning)
Lenalidomide for maintenance
What are helmet cells (AKA schistocytes) seen in?
Microangiopathic diseases
E.g. TTP, HUS, DIC
(Due to fibrin strands ‘cleaving’ the RBC)
How are ‘bite cells’ formed?
Oxidative disease e.g. G6PD deficiency –> Hb denatures –> forms Heinz body –> Heinz body gets ‘bitten out’ by splenic macrophage
What diseases are ‘tear drop’ cells associated with? (2)
Myelofibrosis, thalassaemia
Most common congenital heart defects in Downs Syndrome (top 3)
- Complete AVSD (37%)
- VSD (31%)
- ASD (15%)
CHD seen in up to 50% of Down’s patients, and up to 23% have 2x abnormalities
What is the significance of the NAP1 Clostridium strain?
Hypervirulent strain that produces and additional binary toxin, produces larger amounts of toxins A/b, and has increased antibiotic (esp. quinolone) resistance / decreased cure rates
Which cytokine is associated with increased C. difficile diarrhoea?
IL-8
First line medication for mild Parkinson’s
MAOb inhibitors e.g. Selegiline
Prevent dopamine metabolism
Abatacept target
Binds CD80/86 on APCs - prevents activation of T-cells (used in RA)
True / false: alcohol consumption is protective against renal cell carcionma
True
Scenarios in which to use tetanus immunoglobulin (2)
In a tetanus-prone wound:
- If there is no/unclear history of vaccination
- If the patient is immune compromised
Oestrogen-dependent cancers (2)
Endometrial
Breast
Hormone replacement therapy: contraindication to using oestrogen-only therapy (either oral or transdermal)
Presence of endometrial tissue (due to risk of cancer).
I.e. so only use if they’ve had a hysterectomy
HRT: when to use:
- Oestrogen and continuous progesterone
- Oestrogen and cyclical progesterone
Post-menopausal
Peri-menopausal
Key MMSE domain deficit in Lewy Body dementia
Visiospatial e.g. copying or drawing objects
What is the best test to monitor the treatment of secondary hypothyroidism?
T4
What are the treatment options for catatonia?
Lorazepam
ECT
(NOT anti-psychotics initially - can precipitate NMS)
What can female carriers of X-linked adrenoleucodystrophy present with? (2)
Myelopathy
Polyneuropathy
At what stage to offer CABG instead of PCI?
Two vessel disease involving LAD
Triple vessel disease
(I.e. two vessel disease but just RCA and circumflex still gets PCI instead)
Summarise ECOG classes (0-5)
0: fully fit / independent
1: reduced physical strenuous activity
2: ambulatory + self care, mobile > 50% of day
3: limited self-care, mobile <50% of day
4: fully disabled
5: dead
What components of psoriatic arthritis is MTX useful for? (3)
Arthritis
Skin
IBD
Key arrhythmias of Brugada
AF
VF
Polymorphic VT
(While most other cases of cardiomyopathy have monomorphic VT as rhythm).
Empiric regimen for necrotising fasciitis.
+ if water-immersed
Meropenem OR PipTaz
AND
Clindamycin OR Lincomycin
If water-immersed wound, add ciprofloxacin (for Aeromonas)
Which thyroid test is elevated during sick euthyroid?
Reverse T3
While ‘regular’ T3 is almost always low
Chemo agents with >90% emetogenicity
Cyclophosphamide
Cisplatin
Carmustine
Which type of peptic ulcers need follow-up scope in 8-12 weeks?
Gastric ulcers
Duodenal ulcers have very low malignancy risk
True / False: DMARDs can be used for axial manifestations of ankylosing spondylarthritis
False (DMARDs are only used as second line for PERIPHERAL manifestations)
For axial Sx:
First = NSAIDs and conservative Rx.
Second = anti-TNF or anti-IL-17
What is the mode of inheritance for C9ORF72 and SOD1?
Autosomal dominant
Hypersensitivity allele for abacavir
HLA-B*5701
Hep B post-exposure prophylaxis consists of:
Scenarios / indications.
Vaccination AND immunoglobulin as soon as possible
But only indicated in case where:
- Source is hep B positive or unknown status
- AND recipient is not immune
If source is negative, but recipient is also negative, then just immunise
No action if recipient is known to be immune
How to remember non-nucleoside reverse transcriptase inhibitors
‘-vir’ in the middle of the name e.g. efavirenz, nevirapine
How to remember protease inhibitor drug names
‘-navir’ at the end of the drug name
(‘never (navir) tease a PRO)
(Class associated with increased lipids)
How to remember integrase inhibitor drug names
End with ‘-gravir’
Class associated with increased weight
HIV fusion inhibitors (2)
Maraviroc
Enfuvirtide
How to remember nucleoside reverse transcriptase inhibitors
Everything else not covered by other mnemonics
Which hep B drugs are safe during pregnancy?
Tenofovir or lamivudine, not entecavir
What does the NOD2 gene predispose to?
Ileal crohn’s disease
What is the mechanism of ocrelizumab?
Anti-CD20 (used in MS)
Obinutuzumab mechanism of action
Anti-CD20 (used in follicular lymphoma and CLL)
What targeted agent to use in right-sided, RAS/RAF mutated colorectal cancer?
Bevacizumab (VEGF inhibitor)
What targeted agent to use in left-sided, RAS/RAF wild type colorectal cancer?
Cetuximab, panitumumab (EGFR inhibitors)
Causes of ‘Erlenmeyer Flask Deformity’ on x-ray (4)
Gaucher’s disease (lysosomal storage disorder)
Niemann-Pick disease
Osteopetrosis
Heavy metal poisoning
Formula for VO2max
VO2max = CO(CaO2 - CvO2)
I.e. cardiac output x oxygen utilised
What is the E/a ratio? (3)
Ratio of early diastolic filling (passive) to late atrial filling (active).
Ratio <1 indicates impaired heart relaxation due to reduced early filling
But in severe disease see ratio >2.0 (due to restrictive filling)
What is the E/e’ ratio?
Assessment of LV filling pressure. Value >15 indicates LV diastolic dysfunction.
Positive likelihood ratio formula
+LR = sensitivity / (100 - specificity)
Negative likelihood ratio formula
-LR = (100 - Sensitivity) / specificity
Post-test odds formula
Post test odds = pre-test odds * likelihood ratio
Odds ratio formula
OR = odds in exposure group : odds in control group
What is the 500 rule in diabetes?
Estimates insulin-carb ratio:
500 / total daily insulin
= number of carbs covered by a unit of insulin
What is insulin sensitivity factor + how to calculate
How much one unit of short-acting insulin will lower BSL
ISF = 100 / total daily insulin
Can then use ISF to calculate correction dose:
E.g. if current BSL is 10mM higher than target, then can give 10/ISF units (on top of normal insulin)
Dialysable drugs
'BLAST': Barbiturates Lithium Alcohol/ethylene glycol Salicylates Theophyline
Muscles supplied by median nerve
'LOAF': Lateral 2x lumbricals Opponins pollicis Abductor pollicis brevis Flexor pollicis brevis
Statistical to test to use for:
Qualitative data / binomial data
Chi square
Statistical to test to use for:
Quantitative, one group before/after intervention, normal distribution
Paired t-test
Statistical to test to use for:
Quantitative, one group before/after intervention, not normal distribution
Wilcoxon test (non-parametric test with ONE word)
Statistical to test to use for:
Quantitative, two groups compared, normal distribution
Unpaired t-test
Statistical to test to use for:
Quantitative, two groups compared, not normal distribution
Mann-Whitney test (non-parametric test with TWO words)
Statistical to test to use for:
Quantitative, more than 2 groups
ANOVA - if normal distribution
Kruskal-Wallis - not normal distribution
Hormones that increase appetite (3)
Ghrelin
NPY
AgRP
Markers of bone formation (3)
Bone-specific ALP (BSAP)
N-terminal PROpeptide of type 1 collagen (PINP)
Osteocalcin
(i.e. not TELOpeptides, the rest indicate bone resorption)
Alcohol withdrawal; at what time do seizures peak?
After ~36h
CYP system inducers (6)
Carbamazepine Rifampicin Phenytoin/phenobarbitone St John's wort Smoking
(R, P and S also induce p-glycoprotein system)
Ank spond: most common extra-axial joint involved
Hip
What cell marker on B cell gets bound to induce isotype switching?
CD40
Cell surface marker for T cells
CD3, 4, and 5 +/- CD4 and 8
Cell surface marker for B cells
CD 19, 20
What cell is FOXP3 found on?
Treg
Deficient in IPEX syndrome
What is CD13 found on?
Myeloid cells e.g. AML
Cell surface markers for CLL
CD5, 19
HIV medication that affects mood
Efavirenz
Class-wide side effect of nucleoside reverse transcriptase inhibitors
Lactic acidosis
Systemic sclerosis: antibody associated with ILD
Anti-Scl-70 (diffuse SSc)
Antibody associated with polymyositis
Anti-SRP
Antibody associated with anti-synthetase syndrome
tRNA synthetases (including Jo-1)
Antibodies in type 1 autoimmune hepatitis
ANA
Smooth muscle antibodies
Anti-actin
Anti-SLA/LP (specific, severe)
(Rarely see pANCA)
Antibodies in type 2 autoimmune hepatitis
Anti-LKM
Anti-LC1
ASCA: positive or negative in Crohn’s?
Positive (and negative pANCA)
Opposite in UC
Name the circulating factor in FSGS
suPAR
What do microRNAs do?
Small ssRNAs that bind mRNA and lead to their degradation –> can cause impaired protein production
Which MHC does beta-2 microglobulin go with?
MHC-1
Which Ambler class (re: antibiotic resistance) requires Zinc to work?
Class B
(Thus, also called metallo-beta-lactamase)
(Other classes need serine)
(Class B is treated with aztreonam + ceftazadime/avibactam, or polymyxin regimen e.g. colistin + tigecycline)
‘Gold standard’ test for measuring GFR
Inulin (completely cleared by glomerular filtration - no tubular secretion or reabsorption)
Alzheimers prognostic association of:
- APOE2
- APOE4
Reduced risk
Increased risk
Gene association with Charcot-Marie-Tooth disease
PMP22
Best genetic test for:
- Chromosomal duplication / deletions e.g. Downs
- Reciprocal translocation e.g. BCR-Abl
- Microduplications/microdeletions e.g. Charcot-M-T
Karyotyping
FISH
Array comparative genomic hybridisation
Chemo drug classes affecting M-phase (mitosis) (3)
Taxanes
Vinca alkaloids
Etoposide (also affects G2)
Chemo drug classes affecting G2 phase (1)
Bleomycin
Chemo drug classes that are independent of cell cycle stage (2)
Platinum agents
Alkylating agents
Chemo drug classes that affect S-phase (3)
Antimetabolites
Hydroxyurea
Topoisomerase 1 inhibitors
Using what drug has high association with Nocardia infection?
Leflunomide
Organisms included in TB PCR complex (3)
M. Tb
M. bovis
M. Africanum
Use of ritonavir in HIV
As a protease inhibitor ‘booster’ (inhibits CYP3A4)
HIV medication associated with lipodystrophy
Zidovudine and protease inhibitors
Key side-effects of nevirapine (2)
SJS, severe hepatitis
What did the GEMINI study demonstrate (re: HIV Rx)
2x drug combo might be OK - if well-controlled can step down to Dolutegravir and Lamivudine
Which condition requires liver biopsy for diagnosis
Autoimmune hepatitis
What is obeticholic acid used for?
Second line Rx for PBC if ursodeoxycholic acid ineffective (‘Fernesoid X receptor agonist)
What is the most common type of lymphoma?
DLBCL (31%) - intermediate/aggressive
Follicular (22%) - indolent
What type of Hodgkin lymphoma has:
- Worst prognosis?
- Best prognosis?
Lymphocyte depleted
Lymphocyte predominant (classical)
Route of spread of Hodgkin lymphoma
To contiguous nodal groups (usually above diaphragm)
Chromosomal translocation for DLBCL / new product
t(3;14) –> bcl-6 (new mutant allows DNA errors to accumulate without apoptosis)
Follicular lymphoma: initial treatment regimen
Can watch and wait (GELF criteria)
Otherwise: rituximab OR obinutuzumab + chemo:
CVP vs CHOP vs bendamustine)
Management of diffuse large b cell lymphoma
- Initial
- Relapse
R-CHOP
If relapse: brentuximab or pembrolizumab
Which ‘cell of origin’ type of DLCBL lymphoma has:
- Good prognosis
- Poor prognosis
Germinal centre B-cell = good
Activated B cell = poor
Neutropaenic fever:
- Usual antibiotic
- Antibiotics if shocked / needing ICU
PipTaz (NO added G-CSF acutely)
Gentamicin + Vancomicin + PipTaz (or other anti-pseudomonal)
Renal stone types; order of most-to-least common (5)
Calcium-oxalate (70-80%) Calcium-phosphate (15%) Uric acid (8%) Cystine (1-2%) Struvite (1%)
Struvite = Mg + P + NH4
What are the tests sCD25 and CXCL9 associated with?
Haemophagocytic lymphhistiocytosis
sCD25 = soluble IL-2 receptor
What is anti-MAG associated with?
Distal acquired demyelinating symmetric neuropathy
A CIDP-like disease with high monoclonal IgM (either MGUS or Waldenstroms
First line drug for Aspergillus treatment
Voriconazole
Followed by caspofungin, then amphotericin
General treatment for invasive Candidiasis:
- First line
- Step down Rx
- Resistant disease
Echinocandin
Fluconazole
Amphotericin
What type of radiological findings are seen in UIP? (4)
Sub-pleural reticulation (i.e. peripheral lung)
Disease worse at lung bases
Traction bronchiectasis
Honeycombing
What type of radiological changes are seen in NSIP? (4)
Ground glass change
Sub-pleural sparing
In common with UIP:
Traction bronchiectasis
Basal predominance
What type of pattern is seen in idiopathic pulmonary fibrosis?
UIP
Mutation associated with idiopathic pulmonary fibrosis
MUC5b (50%)
What type of ILD pattern does rheumatoid arthritis have?
UIP
While most other connective tissue diseases will have NSIP or COP
Why is Dravet Syndrome a resistant form of epilepsy?
Mutation in sodium channels (SCN1A gene) so that sodium-channel blockers have no effect
What is the ‘Telomeropathy Syndrome’? and give two examples
Mutation in genes that maintain telomeres –> early age organ dysfunction. Autosomal dominant with anticipation phenomenon, can often affect different organ systems across generations.
Pulmonary fibrosis
Dyskeratosis congenita
Aplastic anaemia
What cell cycle phase do hormonal agents act in?
G1
What protein won’t dipstick urine detect
Non-albumin protein e.g. light chains
Use sulfosalicylic acid test
Key cytokine in gout pathogenesis
IL-1-beta
Mediated by neutrophils / inflammasome
How does BCL-2 work?
Inhibits cell apoptosis
What does streptococcal M-protein mimic?
Cardiac myosin
Steroid effect on bone:
- Acute
- Chronic
Increase resorption (inhibits OPG and stimulates RANK)
Decreases formation (reduces proliferation/differentiation and increases apoptosis of osteoblasts)
dsDNA staining pattern
Homogenous
Which insulins bind to albumin (2)
Detemir
Degludec (ultra-long-acting)
How does lactulose reduce encephalopathy
Substrate for bacteria –> reduced pH –> increased NH4+ (which is non-absorbable)
What part of internal capsule is the corticospinal tract in?
Posterior limb
What chromosome is amyloid precursor protein on?
Ch 21
Which interleukin is associated with Mendelian Susceptibility to TB
IL-12
Nerves supplying bladder (3)
Pelvic nerve (PNS) –> ACh to M3
Hypogastric nerve (SNS) –> NA to beta-3 and alpha 1
Pudendal nerve (somatic) –> ACh to nicotinic receptor
What causes depletion of substance P
Capsaicin
What does Ki-67 indicate?
Cell proliferation
Cerebellopontine angle lesions affect which CN’s
V, VII and VIII
E.g. Schwannoma or meningioma
Pizotifen:
- Mechanism
- Side-effect
Serotonin blocker
Weight gain
Essential thrombocytosis mutations, common to least common (3)
JAK2 (40%)
CAL-R (15-30%)
MPL (4-8%)
Key criteria (Ghent criteria) for Marfan’s
2 of 3 of:
- Aortic distension/dissection
- Ectopia lentis (up / out)
- FBN1 gene
Key lesion to distinguish L5 lesion vs common peroneal
Ankle inversion weakness (=L5)
Cells in HLH pathogenesis (2)
NK cells that fail to inactivate over-stimulated macrophages
Cell type in clozapine myocarditis
Eosinophils
Cranial nerves with parasympathetic fibres
III (pupil constriction)
VII (lacrimal / salivary glands)
IX (parotid gland)
X (vagus)
Type B nerve fibres carry
Preganglionic signals to autonomic nervous system
True / False: transthyretin causes renal amyloidosis
False
Cytokine implicated in periodic fever syndromes
IL-1
Best test for working memory
Digit span forward
Medication hierarchy to treat akathisia (3)
- Beta blocker
- Benztropine
- Benzodiazepine
‘Storiform fibrosis’ refers to what diagnosis
IgG4 deposition disease
Most common side-effect of oseltamivir
Nausea / vomiting (15%)
Length of PPI therapy for NSAID-induced ulcer
8-12 weeks
UTI treatment in pregnancy (3)
Nitrofurantoin
Cephalexin
Trimethoprim (2nd/3rd trimester)
Most common gentamicin toxicities (2)
Oscillopsia, imbalance
Rare to have hearing loss, mainly tinnitus
Type III MI definition
MI resulting in death without biomarkers
What is the primary tyrosine kinase in systemic mastocytosis?
Kit (usually lost in other blood cancers)
Most common mutation in Duchenne’s
Exon deletions
Enzyme affected in acute intermittent porphyria
Inheritance
How does Hemin work?
Porphobilinogen deaminase
(Autosomal dominant)
Rx = Hemin - reduces ALAS1 activity –> reduced build-up of haem precursors
Why does 3rd nerve palsy give bigger ptosis than Horner’s?
3rd nerve palsy affects levator palpebrae superioris, while in Horners, only the superior tarsal muscle is affected.
Features suggesting midline cerebellar lesion (7)
Gait ataxia Imbalance Truncal ataxia Leg dysmetria Ocular signs Head bobbing Vertigo
(Other symptoms caused by hemispheric lesion)
Signalling pathway of PTH to cause increased resorption
- PTH released
- Acts on osteoblast
- Osteoblast increased RANK-L
- Binds to RANK on osteoclast, leading to differentiation / activation
Osteoblast also reduces OPG in response to PTH
Normal role of osteoprotegerin
Inhibits / decoy against RANK-L, thereby reducing osteoclast activation
Molecule mutated in eczema
Fillagrin
Common site for metastatic lesions for rectal cancer
Lungs (due to drainage into IVC, rather than portal system)
Warm autoimmune haemolytic anaemia
- Antibody
- Location
IgG
Extravascular
Cold autoimmune haemolytic anaemia
- Antibody
- Location
IgM / C3
Intravascular
Causes of warm AIHA (4)
Primary / Idiopathic
Lymphoproliferative disease e.g. CLL, NHL
Connective tissue disorders
Methyldopa, other drugs
Causes of cold AIHIA (4)
Primary / idiopathic
Mycoplasma
EBV
Lymphoma
Antibiotics that inhibit 30S subunit (2)
Aminoglycosides
Tetracyclines
Antibiotics that inhibit 50S subunit
Macrolides
Clindamycin (lincosamide)
Linezolid (oxazolid)
Chloramphenicol
Mechanism of Amphotericin / Polyenes
Impairs membrane function by binding to ergosterol –> increased permeability
Mechanism of ‘azole’ anti-fungals
Prevent ergosterol synthesis (via inhibition of C-14-alpha demethylase)
When to use tetanus Ig (2)
No prior immunisation
Immunocompromised
(No vaccine needed if last one given <5 years ago)
Hormone replacement therapy, when to use:
- E2 and continuous P
- E2 and cyclical P
- Unopposed E2
Post-menopause
Peri-menopause
Only if prior hysterectomy (due to risk of endometrial cancer if unopposed estrogen exposure)
How to monitor secondary hypothyroidism treatment
T4 levels
True / False: CD20 is expressed on plasma cells
False - hence why rituximab doesn’t cause depletion of immune memory / can maintain normal IgG level
What type of GN has highest association with renal vein thrombosis
Membranous
What symptoms can female carriers of x-linked adrenoleucodystrophy have (2)
Myelopathy
Neuropathy
Treatments for catatonia (2)
Benzo’s
ECT
Most common cause of genetic ALS
C9ORF72
Associated with FTD / tau-opathy
Long-term complication after repair of tetralogy of Fallot
Pulmonary incompetence
Medication to treat pan-resistant ESBL
Colistin (alongside tigecycline)
During abiraterone treatment, what concurrent medication needs to be given?
Glucocorticoids
What does Lugol’s iodine do?
Prevents release of pre-formed thyroid hormone
What condition causes a thyroid bruit?
Grave’s disease
What outcomes are improved by using CPAP? (4)
Less MVAs
Improved QoL
Better sleep scores / readings
Less GORD
Ratio for oxynorm to PO morphine
1.5
Most sensitive test for diagnosis of TB / hierarchy of tests for sensitivity
3x consecutive TB sputum cultures
Culture > NAAT > smear
Medications for essential tremor (2)
Primidone
Propranolol
Route of breast cancer spread if:
- ER+
- HER2+
To bones
To viscera
Infective cause of coronary artery aneurysms
Syphilis
Best ACEi to use in diffuse scleroderma
Captopril (not ARBs)
Medications for orbital cellulitis (2)
Flucloxacillin AND ceftriaxone
What does a linear lucency through the lateral cortex of the subtrochanteric region suggest?
Atypical femoral fracture
What is the ‘double contour sign’ on US diagnostic of?
Gout
Can also see cloudy area on US
Core features of Lewy Body Dementia (3)
Cognitive fluctuation
Visual hallucinations
REM sleep disorder
What electrolyte abnormality can trimethoprim cause?
Hyper-K+
Which Parkinson Plus syndrome is associated with axial rigidity and early falls
PSP
Joints affected in haemochromatosis
2nd and 3rd MCPJs (can have erosive arthritis)
True / False: Having diabetes is protective against development of a new AAA
True
Smoking = greatest risk factor
What is the gender difference for developing / extension of AAA
Male - higher risk of getting AAA
Female - higher risk of extension of AAA
What is a bilateral vestibular Schwannoma associated with?
NF2 (mutation in merlin/schwannomin protein which is normally a tumour suppressor)
What condition is dual energy CT used for to diagnose?
Gout
On ECHO, what does fractional shortening indicate?
Systolic failure (a correlate of ejection fraction)
Mechanism of Ivacaftor
Increases CFTR activity / improves Cl- gating
Mechanism of Lumacaftor
Improves folding of CFTR protein
What is the most effective complement-fixing Ab
IgM
What drug inhibits inosine monophosphate dehydrogenase?
Mycophenolate
What does Muromonab bind to?
CD3 (on T cell surface)
Used as immune suppressant after solid organ transplant
‘Trauma’ medication that may be useful in hereditary angioedema.
Tranexamic acid (by reducing amount of fibrin breakdown products)
Features of NF1 (6)
Cafe au lait Axillary freckling Lisch nodules (most common sign) Bone lesions Tumours e.g. fibromas Neurologic symptoms
True/false: activated charcoal is effective in lithium poisoning.
False - heavy metals, alcohol and inorganic ions do not adsorb well to charcoal
What does bilateral absence of the vas deferens (in CF) result in?
Obstructive azoospermia
Antibiotic class that interacts with tacrolimus
Macrolide
Normal Pulmonary Capillary Wedge Pressure (PCWP)
6-15mmHg
Adverse effect of Mg2+ in resus
Hypotension and bradycardia
How does abiraterone work in prostate cancer?
Inhibits synthesis of testosterone (at level of adrenals and at level of cancer cells)
Aspergillus prophylaxis
Posaconazole or itraconazole
Below what spinal level do people no longer get autonomic dysreflexia / why
T6 - due to compensatory vasodilatation of splanchnic circulation
Outcomes of NIV in motor neuron disease:
- Bulbar disease
- Non-bulbar disease
Increased QoL
Improved survival
CrCl cut-offs for anti-coagulants:
- Warfarin
- Dabigatran
- Rivaroxaban
- Apixaban
No limit
<30
<15
<15
Most common cancers in Peutz-Jeghers syndrome
Colon, pancreas, breast
Peutz-Jeghers inheritance
Autosomal dominant (STK11 gene)
Indications for acute ERCP in pancreatitis (3)
Cholangitis
CBD obstruction
Increasing LFTs
(Otherwise no role in first 24h, fluids have greatest survival benefit)
Features of essential tremor (5)
Bilateral Action tremor No other neuro Fine/high frequency Worse with stress, better with EToH
Urease-producing organisms (2)
Proteus
Klebsiella
Antibiotic for pre-orbital cellulitis
Flucloxacillin
Type of malignancy associated with BRAF-inhibitor use (as in, a side-effect)
Skin squamous cell carcinoma
3x most common cardiac abnormalities in Turner Syndrome
Most common = bicuspid AV
2nd = coarctation
3rd = pulmonary stenosis
What does a U-wave correlate with?
Hypokalaemia
Also hypothermia or hypocalcaemia
T-cell maturation:
- Positive selection
- Negative selection
Binds MHC-1/-II –> survive
Apoptosis if binds self-antigens
Factors involved in small initiation of clotting cascade
Tissue factor and VII
Factors involved in amplification of clotting cascade
Xa and V
Cough reflex:
- Afferent fibre
- Synapse point
- Efferent fibre
Vagus nerve
Medulla
Vagus + phrenic + spinal
Goserilin / Leuprolide
- Mechanism
- What to watch out for in prostate cancer
- Cancer-related contraindications (2)
GnRH agonist
‘Flare’ phenomenon in first two weeks - manage with concurrent androgen receptor blocker e.g. bicalutamide
Urinary tract obstruction, painful bone mets
Degarelix mechanism
GnRH antagonist - avoids flare phenomenon
What to give alongside abiraterone therapy
Glucocorticoids (due to increased shunting towards mineralocorticoid synthesis)
Cancer associated with exposure to unopposed oestreogen
Endometrial, breast
Enzyme that is weakly inhibited by paracetamol
COX-1
Thus can cause flare of aspirin-exacerbated respiratory disease in some people
Upper limb critical actions:
- C5
- C6
- C7
- C8
- T1
Elbow flexion
Wrist ext
Elbow ext
Finger flex
Finger abduction
Draw diagram of sciatic nerve divisions and motor/sensory supply
Sciatic (L4-S3) - knee flexion, sensation below knee
Tibial (posterior) branch –> plantarflexion / inversion / sole of foot
Common peroneal
- Deep branch –> dorsiflexion / 1st webspace
- Superficial branch –> eversion / dorsum / lateral leg
Summary table for foot drop:
- Sciatic
- L4/5
- Common peroneal
Sciatic - loses eversion, inversion and ankle jerk
L4/5 - preserved ankle jerk (it is S1/2)
Common peroneal - only loses eversion
Motor component of ankle jerk reflex
S1/2
Venetoclax mechanism / use
Binds / inhibits BCL-2
Used in CLL with del(17p)
Target of Benralizumab
IL-5R (used in asthma)
Interventions with a proved benefit in reducing falls (4)
Group or home exercises (balance, strength)
Home safety interventions
Multi-factorial assessment
Tai Chi
Size cut-off of lesions for liver transplantation for HCC
3x lesions, less than 3cm
OR
1x lesion <5cm (Milan)
Or
Cumulative tumour <8.5cm (UCSF criteria)
TKIs for HCC (2)
Sunitinib
Lenvatinib
Used in stage C disease
Metformin
- Mechanism
- Key ADRs (3)
Activation of AMP-activated protein kinase (AMPK) → increases insulin sensitivity
GI upset, low B12 (can be reversed by giving calcium supplementation), lactic acidosis
Sulfonylureas
- Mechanism
- Key ADRs (2)
Close ATP-sensitive K+ channels → stimulate insulin secretion
Hypoglycaemia, weight gain
Thiazolidinediones (‘glitazones’)
- Mechanism
- Key ADRs (2)
PPARy agonist in adipocytes
Weight gain, fluid retention (contraindicated in CHF)
DPP-4 inhibitors (‘gliptins’)
- Mechanism
- Key ADRs (1)
Inhibits DPP-4 which normally breaks down incretins GLP-1 and GIP
Pancreatitis
Which SGLT-2i is associated with highest euDKA risk?
Canagliflozin (HR3.58)
Genetic causes of phaeochromocytoma (4)
MEN2
VHL
SDH mutation (paraganglioma)
NF1
How to monitor for phaeochromocytoma recurrence after surgery (2)
Chromogranin A
Metanephrines
Follow-up for adrenal incidentaloma with initial negative work-up (2)
Annual hormone screen for 5 years
Imaging at 3-6 months, then annually for up to 2 years
What happens to V/Q ratio from apex to base?
Both V and Q increase as you go to base. Q increases more than V, thus the V/Q ratio lowers. At apex, it is ~2.1 At middle, ~1.0 At base, ~0.3
Layers of the epidermis from out to in (5)
Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale
Muscle controling active expiration
Internal intercostals
Herbal OTCs that cause liver injury (4)
Black cososh (menopausal Sx)
Valerian (sleep, relaxation)
Chinese herbal meds
Green tea
Where / what makes ACE in sarcoidosis?
Macrophages in granulomas
Type of genetic inheritance diseases that can be ‘cured’ with gene therapy
Autosomal recessive - replaced loss of function
What hormone mediates sweating?
Adrenaline
Key parameter to monitor in GBS re: respiratory crisis
FVC - intubate when <20ml/kg
Agent to use in severe serotonin syndrome
Cyproheptadine
Agent to use in severe NMS
Bromocriptine
Indications for ICS in COPD (3)
Frequent exacerbations/hospitalisations
Eosinohilia
Asthma component
Brain region to consider if pure motor stroke
Internal capsule (blood supply from lenticulostriate arteries)
Brain region to consider if pure sensory stroke
Thalamus (blood supply from PCA)
‘Bulbar’ nerves
IX, X, XI, XII - exit at the medulla
How to exclude medial rectus muscle lesion as being the cause of INO
Get patient to converge eyes - now just need bilateral CN III signal
What do nerve roots exiting the spinal cord carry?
- Anterior root
- Posterior/dorsal root
Motor (cell bodies live in the anterior horn)
Sensory (cell bodies of sensory cells live in the dorsal root ganglion)
Where does the spinothalamic tract decussate?
1-2 levels above where they enter the spinal cord
‘Cape’ or ‘vest’ sensory loss distribution is suggestive of…
Central cord lesion e.g. syringomyelia
Outcome of anterior cord syndrome
1x anterior spinal artery supplies anterior 2/3 of cord –> ischaemia affects everything other than dorsal columns –> all modalities affected except proprioception and vibration
Features that make a drug dialysable (3)
Low protein binding
Low Vd
Small molecular weight
(Also note, increasing plasma clearance will DECREASE dialysis clearance rates)
