random Flashcards
CHA2DS2-VASc score?
Used to determine the need to anticoagulate a patient in atrial fibrillation
ABCD2 score?
Prognostic score for risk stratifying patients who’ve had a suspected TIA
NYHA score?
Heart failure severity scale
DAS28 score?
Measure of disease activity in rheumatoid arthritis
DAS stands for ‘disease activity score’ and the number 28 refers to the 28 joints that are examined in this assessment.
Child-Pugh classification?
A scoring system used to assess the severity of liver cirrhosis
Wells score?
Helps estimate the risk of a patient having a deep vein thrombosis
MMSE?
Mini-mental state examination - used to assess cognitive impairment
HAD scale?
Hospital Anxiety and Depression (HAD) scale - assesses severity of anxiety and depression symptoms
PHQ-9?
Patient Health Questionnaire - assesses severity of depression symptoms
GAD-7?
Used as a screening tool and severity measure for generalised anxiety disorder
Edinburgh Postnatal Depression Score?
Used to screen for postnatal depression
SCOFF score?
Questionnaire used to detect eating disorders and aid treatment
Sick
Control
One stone (14 lbs./6.5 kg.)
Fat
Food
AUDIT scoring?
Alcohol screening tool
Alcohol Use Disorders Identification Test
CAGE questionnaire?
alcohol screening tool
cut down/ annoyed/ guilty/ eye-opener
FAST screening?
alcohol screening tool
(also a mnemonic to rmb symptoms of stroke)
CURB-65 score?
Used to assess the prognosis of a patient with pneumonia
Epworth Sleepiness Scale?
Used in the assessment of suspected obstructive sleep apnoea
IPSS?
International prostate symptom score
Gleason score?
Indicates prognosis in prostate cancer
Bishop score?
Used to help assess the whether induction of labour will be required
Waterlow score?
Assesses the risk of a patient developing a pressure sore
FRAX score?
Risk assessment tool developed by WHO which calculates a patients 10-year risk of developing an osteoporosis related fracture
Ranson criteria?
Acute pancreatitis
ratio of chest compressions to ventilation?
30:2
Defibrillator assesses a rhythm of PEA/ asystole
-> mx?
continue CPR for 2 mins then reassess rhythm
IV adrenaline every 3-5 min
defibrillator assess a shockable rhythm ie. pulseless VT/VF
mx?
a single shock followed by 2 mins of CPR
adrenaline 1 mg is given once chest compressions have restarted after the third shock and then every 3-5 minutes.
give amiodarone after 3 shocks
Biochemistry of dehydration?
↑↑ U, ↑Cr
↑albumin
↑HCT
Biochemistry of Low GFR?
↑U, ↑Cr, ↑H, ↑K, ↑urate
↑PO4, ↓Ca
Biochemistry of tubular dysfunction?
Normal U and Cr
↓K, ↓urate, ↓PO4, ↓HCO3
biochemistry of SIADH?
↓Na
↓ serum osmolality, ↑ urine osmolality (>500), ↑ urine Na
Biochemistry of DI?
↑Na, ↑ serum osmolality, ↓ urine osmolality
Biochemistry of Conn’s?
↓K, ↑Na, ↑HCO3
Biochemistry of Addisons?
↑K, ↓Na
Biochemistry of cholestasis?
↑↑ALP, ↑↑GGT, ↑Bilirubin, ↑AST
biochemistry of alcoholic hepatocellular disease?
AST:ALT>2, ↑GGT
biochemistry of viral hepatocellular disease?
ALT>AST
biochemistry of thiazide and loop diuretics?
↓Na, ↓K, ↑HCO3, ↑U
presentation of hypoNa?
<135: n/v, anorexia, malaise
<130: headache, confusion, irritability
<125: seizures, non-cardiogenic pulmonary oedema
<115: coma and death
Causes of hypovolaemia hypoNa?
Urine Na > 20 mM (= renal loss)
- diuretics
- addisons
- osmolar diuresis e.g. glucose
- renal failure
Urine Na < 20 mM
diarrhoea
vomiting
burns
Causes of hypervolaemic hypoNa?
Cardiac failure
Renal failure
Nephrotic syndrome
Cirrhosis
causes of euvolaemic hypoNa?
urine osmolality >500
SIADH
urine osmolality <500
- water overload
- severe hypothyroidism
- Addisons
Mx of hyponatraemia?
Correct the underlying cause
Replace Na and water at the same rate they were lost
- Too fast → central pontine myelinolysis
- Chronic: 10mM/d
- Acute: 1mM/hr
Asymptomatic chronic hyponatraemia -> Fluid restrict
Symptomatic / acute hyponatraemia / dehydrated -> Cautious rehydration with 0.9% NS
If hypervolaemic consider frusemide
Emergency: seizures, coma -> Consider hypertonic saline (e.g. 1.8%)
features of SIADH?
Concentrated urine: Na>20mM, osmolality >500
HypoNa or plasma osmolality <275
Absence of hypovolaemia, oedema or diuretics
causes of SIADH?
Resp: SCLC, pneumonia, TB
CNS: meningoencephalitis, head injury, SAH
Endo: hypothyroidism
Drugs: cyclophosphamide, SSRIs, CBZ
Mx of SIADH?
Rx cause and fluid restrict
Vasopressin receptor antagonists
- Demeclocycline
- Vaptans
presentation of hyperNa?
Thirst
Lethargy
Weakness
Irritability
Confusion, fits, coma
Signs of dehydration
Causes of hyperNa?
Usually caused by dehydration (↓ intake or ↑ loss)
Hypovolaemic
GI loss: diarrhoea, vomiting
Renal loss: diuretics, osmotic diuresis (e.g. DM)
Skin: sweating, burns
Euvolaemic
↓ fluid intake
DI
Fever
Hypervolaemic
Hyperaldosteronism (↑BP, ↓K, alkalosis)
Hypertonic saline
Mx of hyperNa?
Give water PO if possible
Otherwise, 5% dextrose IV slowly
Use 0.9% NS if hypovolaemic or Na >170mM
-> Causes less marked fluid shifts
Aim for Na ↓ ≤12mM/d
Too fast → cerebral oedema
Causes of Hyperkalaemia?
artefact:
haemolysis
K2EDTA contamination from FBC bottle
Leucocytosis, thrombocytosis
Drip arm
internal distribution
acidosis
low insulin
cell death/ tissue trauma/ burns
digoxin poisoning
suxamethonium
decreased excretion:
oliguric renal failure
Addisons
Drugs: ACEi, NSAIDs, K+ sparing diuretics
increased input:
massive transfusion
excessive K therapy
Mx of hyperkalaemia?
non-urgent: if K+ 6-6.5 w no ECG changes
- Stop all K containing/ sparing drugs
- Low K diet
- Ensure adequate hydration and monitor UO
- Tx hypotension
- Give iv fluids if dehydrated
- Monitor renal fn
- consider Calcium resonium to decrease K
Emergency: evidence of myocardial instability or K>6.5
- 10ml 10% calcium gluconate
- 100ml 20% glucose + 10u insulin (Actrapid)
- Salbutamol 5mg nebulizer
- Haemofiltration (usually needed if anuric)
- Calcium resonium 15g PO or 30g PR
symptoms of hypoK?
Muscle weakness
Hypotonia
Hyporeflexia
Cramps
Tetany
Palpitations
Arrhythmias
ECG changes of hypoK?
Result from delayed ventricular repolarisation
Flattened / inverted T waves
Prominent U waves (after T waves)
ST depression
Long PR interval
Long QT interval
causes of HypoK?
Internal Distribution
Alkalosis
↑ insulin
β-agonists
↑ Excretion
GI: vomiting, diarrhoea, rectal villous adenoma
Renal: RTA (esp. type 2), Bartter syn.
Drugs: diuretics, steroids
Endo: Conn’s syn., Cushing’s syn.
↓ Input
Inappropriate IV fluid management
Mx of hypoK?
1mM K ↓ = ~200-300mmol total deficit
Don’t give K if oliguric
Never give STAT fast bolus
Mild: K >2.5
Oral K supplements
≥80mmol/d
Severe: K <2.5 and/or dangerous symptoms
IV KCl cautiously
10mmol/h (20mmol/h max)
Best to give centrally (burning sensation peripherally)
Max central conc: 60mM
Max peripheral conc: 40mM
Mg Replacement
Pts. are often Mg deplete too
Until Mg is replaced the K will not return to normal levels despite K replacement
Give empiric Mg replacement
in hypoK, what other electrolyte do u also need to correct?
Mg replacement
Role of Mg in PTH release?
low Mg prevents PTH release
may -> low Ca
symptoms of hypocalcaemia?
tetany
perioral parasthesiae
carpopedal spasms
Cardiomyopathy (↑ QTc -> TdP)
seizures
confusion
dermatitis: atopic, exfoliative
signs of HypoCa?
Trousseau’s sign:
BP cuff inflated + held in place for 3 minutes-> occlude the brachial artery. In the absence of blood flow, the patient’s hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm
Chvostek’s sign: facial n is tapped in front of tragus -> facial muscles on the same side of the face will contract momentarily due to hyperexcitability of nerves.
causes of hypoCa?
With ↑ PO4
CKD
Hypoparathyroidism / pseudoyhpoparathyroidism
↓Mg Acute rhabdomyolysis (muscle Ca deposition)
With normal or ↓ PO4
Osteomalacia
Active pancreatitis
Respiratory alkalosis
Mx of hypoCa?
Mild
Ca 5mmol QDS PO
Daily Ca levels
CKD
Alfacalcidol (1-OH-Vit D3)
Severe
10ml 10% Ca gluconate IV (2.25mmol) over 30min
Repeat as necessary
presentation of hyperCa?
Stones
Renal stones
Polyuria and polydipsia (nephrogenic DI)
Nephrocalcinosis
Bones
Bone pain
Pathological #s
Moans: depression, confusion
Groans
Abdo pain
n/v and constipation
Pancreatitis
PUD (↑gastrin secretion)
high BP
decreased QT interval
Causes of hyperCa?
Most commonly malignancy or 1O HPT
With ↑ PO4
↑ ALP (e.g. ↑ bone turnover)
Bone mets: thyroid, breast, lung, kidney, prostate, colon
Sarcoidosis
Thyrotoxicosis
Lithium
Normal ALP
Myeloma
Hypervitaminosis D
Sarcoidosis
Milk alkali syn.
With normal or ↓ PO4
1O or 3O HPT
Familial benign hypercalciuria: AD, ↑ Ca-sensing receptor set-point
Paraneoplastic: PTHrP (but ↓PTH)
Ix of HyperCa?
↑PTH = 1o or 3O HPT
↓PTH: most likely Ca
FBC, protein electrophoresis, CXR, bone scan
mx of hyperCa?
Dx and Rx underlying cause
Rehydrate
1L 0.9% NS/4h
Monitor pts. hydration state
Frusemide
Only start once pt. is volume replete
Calciuric + makes room for more fluids
Bisphosphonates:
Ca bisphosphonate can’t be resorbed by osteoclasts
Only used in hypercalcaemia of malignancy
Can obscure Dx as → ↓Ca, ↓PO4 and ↑PTH
E.g. Pamidronate, Zoledronate (IV)
risk factors of osteoporosis?
SHATTERED
Steroids
Hyperthyroidism, HPT, HIV
Alcohol and Cigarettes
Thin (BMI <22)
Testosterone Low
Early Menopause
Renal / liver failure
Erosive / inflam bone disease (e.g. RA, myeloma)
Dietary Ca low / malabsorption
T score vs Z score?
T: no. of SDs away from youthful average
Z: no. of SDs away from age-matched average
indications for DEXA scan?
Low-trauma #
Women ≥65yrs w one or more risk factors
Before giving long-term steroids (>3mo)
Parathyroid disorders, myeloma, HIV
Bisphosphonates SEs?
GI upset
Oesophageal ulceration / erosion: Take w plenty of water on an empty stomach and refrain from lying and don’t eat for 30min.
Diffuse musculoskeletal pain
Osteonecrosis of the jaw
Mx of osteoporosis?
Decision to instigate pharmacological Rx is based upon age, RFs, and BMD.
FRAX can estimate 10yr # risk
Conservative
Stop smoking, ↓ EtOH
Wt. bearing or balancing exercise (e.g. Tai Chi)
Ca and vit-D rich diet
Home-based fall-prevention program w visual assessment.
Primary and secondary prevention of #s
Bisphosphonates: alendronate is 1st line
Ca and Vit D supplements: e.g Calcium D3 Forte
Strontium ranelate: bisphosphonate alternative
Alternative medications for 2O prevention of osteoporotic #s?
Raloxifene: SERM, ↓ breast Ca risk cf. HRT
Teriparetide: PTH analogue → new bone formation
Denosumab: anti-RANKL → ↓ osteoclast activation
diagnostic ix of Hereditary spherocytosis?
cryohaemolysis test snd EMA binding test
Osmotic fragility test
mx of osteomalacia?
Dietary: Calcium D3 Forte
Malabsorption or hepatic disease: Vit D2 (ergocalciferol) PO, Parenteral calcitriol
Renal disease or vit D resistance:
1α-OH-Vit D3 (alfacalcidol)
↓1,25-(OH)2 Vit D3 (calcitriol)
Monitor plasma Ca
Ix of Heart Failure?
Previous myocardial infarction
arrange echocardiogram within 2 weeks
No previous myocardial infarction
measure serum natriuretic peptides (BNP)
if levels are ‘high’ arrange echocardiogram within 2 weeks
if levels are ‘raised’ arrange echocardiogram within 6 weeks
in tumour lysis syndrome, apart from high K+, phosphate and low Ca
what else do u need?
one or more of:
increased serum creatinine (1.5 times upper limit of normal)
cardiac arrhythmia or sudden death
seizure
what supportive therapy can you provide to pt w dementia?
offer ‘a range of activities to promote wellbeing that are tailored to the person’s preference’
cognitive stimulation therapy
reminiscence therapy and cognitive rehabilitation
memory clinic
mx of mumps?
rest
paracetamol for high fever/discomfort
notifiable disease
what antibiotic can cause a disulfiram-like reaction when combined w ethanol?
Metronidazole
+ Cefoperazone, a cephalosporin
Clinical features of this include head and neck flushing, nausea and vomiting, sweatiness, headache and palpitations.
mx of secondary pneumothorax <1cm and asymptomatic?
management is with admission, high flow oxygen, and reassessment in 24 hours.
what should you assess for before offering a pt azathioprine or mercaptopurine?
TPMT activity
thiopurine methyltransferase
defect-> enhanced bone marrow toxicity which may cause myelosuppression, anemia, bleeding tendency, leukopenia & infection
Strong assoc of syringomyelia with?
Arnold-Chiari malformation
mx of essential tremor?
propranolol is first-line
most common cause of titubation (head tremor)?
essential tremor
1st line mx of chronic heart failure?
ACEi + BB
first line ix of acute mesenteric ischaemia (before CT)?
bloods: raised lactate (lactic acidosis)
mx of acute haemolytic transfusion reaction?
immediate transfusion termination, generous fluid resuscitation with saline solution and informing the lab
mx of latent TB?
3 months of isoniazid (with pyridoxine) and rifampicin OR 6 months of isoniazid (with pyridoxine)
concurrent use of BB and verapamil?
may precipitate severe bradycardia
Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) and beta blockers are both negatively inotropic and their combined effects can cause severe bradycardia and even asystole.
main indications for placing a chest tube in pleural infection?
frankly purulent or turbid/cloudy pleural fluid
The presence of organisms identified by Gram stain and/or culture
Pleural fluid pH < 7.2
predisposing factors to obstructive sleep apnoea?
obesity
macroglossia: acromegaly, hypothyroidism, amyloidosis
large tonsils
Marfan’s syndrome
mx of obstructive sleep apnoea?
weight loss
CPAP is first line for moderate or severe OSAHS
intra-oral devices (e.g. mandibular advancement) may be used if CPAP is not tolerated or for patients with mild OSAHS where there is no daytime sleepiness
which bones does Pagets disease tend to affect?
axial skeleton
- ie pelvis, lumbar spine, skull, femur, tibia
complications of Paget’s disease?
Nerve compression: deafness, radiculopathy
High output CCF
Osteosarcoma (<1% after 10yrs) -> sudden onset or worsening of bone pain
Ix of Pagets Disease?
HIGH ALP
Bone scan: hot spots
X-ray:
bone enlargement, sclerosis, patchy cortical thickening, deformity, wedge-shaped lytic lesions, osteoporosis circumscripta (well defined lytic skull lesions)
Biochemistry of pts w osteoporosis?
usually Ca, PO4, Alk Phos, PTH all normal
*Alk Phos may be raised if recent #
Looser’s zones on Xrays?
pseudofractures
found in osteomalacia/ Rickets
A band of bone material of decreased density may form alongside the surface of the bone. Thickening of the periosteum occurs. The formation of callouses in the affected area is also common. This gives the appearance of a false fracture.
Biochemistry of Osteomalacia?
Ca LOW
PO4 Low
PTH high
Alk Phos high
Biochemistry of Rickets
Ca Normal or Low
PO4 low
PTH high
ALk phos High
Biochemistry of primary hyperparathyroidism?
Ca high
PO4 low
PTH inappropriately normal/ High
Alk phos High
causes of primary hyperPTH?
most common 80% Parathyroid adenomas
20% gland hyperplasia
<0.5% parathyroid ca
Biochemistry of secondary HyperPTH
Ca low
PO4 high
PTH high
Alk Phos high
Biochemistry of tertiary hyperPTH?
Ca high
PO4 low/ n
Alk Phos high
PTH high
Biochemistry of hypoPTH?
Ca low
PO4 high
PTH inappropriately N/ low
Alk phos N
cause of hypoPTH?
surgical
autoimmune
congenital - DiGeorge’s
Biochemistry of Paget’s Disease?
Ca normal
PO4 normal
ALK phos HIGH
PTH normal
Classification of hyperlipidaemia?
Common Primary Hyperlipidaemia
- 70%
- Dietary and genetic factors
- HIGH LDL only
Familial primary hyperlipidaemia
- multiple phenotypes
- high risk of CVD
Secondary hyperlipidaemia:
- high LDL: nephrotic syndrome, cholestasis, hypothyroidism, Cushing’s, Drugs: thiazides, steroids
Mixed high LDL and high TG: T2DM, Alcohol, Chronic renal failure
Causes of secondary hyperlipidaemia?
high LDL: nephrotic syndrome, cholestasis, hypothyroidism, Cushing’s, Drugs: thiazides, steroids
Mixed high LDL and high TG: T2DM, Alcohol, Chronic renal failure
Types of Familial primary hyperlipidaemias?
1o hypercholesterolaemia:
commonest, ApoB (LDL receptor) defect -> high LDL-C
Combined hyperlipidaemia:
high LDL and TG
Lipoprotein lipase deficiency: high chylomicrons
Hypertriglyceridaemia
presentation of hyperlipidaemia?
CVD
Xanthomata:
- corneal arcus
- xanthelasma on eyelids
- planar: orange streaks in palmar creases
- tuberous: plaques on elbows, knees (over joints)
- tendons
Pancreatitis
Ix of hyperlipidaemia?
Plasma cholesterol
Plasma HDL + LDL
Fasting TGs
TC:HDL ratio is best predictor of CV risk
Aims of tx for hyperlipidaemia?
Total cholesterol < 4
Total cholesterol: HDL ratio < 4
LDL < 2
Mx of Hyperlipidaemia?
Lifestyle changes: weight loss, increase exercise, diet (increase fibre, fruit and veg, less sat fat)
1st Line: Statins
e.g. Simvastatin 40mg PO nocte
HMG-CoA reductase inhibitors -> decrease cholesterol synthesis
2nd line;
fibrates: PPARa antagonists, decrease TGs
Ezetimibe: inhibits cholesterol absorption
Niacin/ Nicotinic acid: raises HDL, lowers LDL
What is Porphyria Cutanea Tarda?
Commonest porphyria
Cutaneous manifestations only
Uroporphyrinogen decarboxylase deficiency
photosensitivity: blistering skin lesions
facial hyperpigmentation and hypertrichosis
ix of porphyria cutanea tarda?
high Urine and serum porphyrins
high serum ferritin
Precipitants of porphyria cutanea tarda?
sunlight
alcohol
Mx of porphyria cutanea tarda?
Avoid sun
Phlebotomy/ iron chelators
chloroquine
Precipitants of acute intermittent porphyria?
P450 inducers: anti epileptics, alcohol, OCP/ HRT
infection/ stress
fasting
pre-menstrual
Ix of acute intermittent porphyria?
Urine sample!
keep it shielded from light
Increased ALA and PBG in urine
‘port wine urine’ as seen by person
when PBG gets oxidised to porphobilin (deep yellow -> purple)
what are porphyrias?
diseases due to deficiencies in the enzymes of the Haem biosynthesis pathway. -> overproduction of toxic haem precursors leading to 3 presentations. 1. acute neuro-visceral 2. acute cutaneous 3. chronic cutaneous
ALA Synthase deficiency
ALA synthase produces ALA (5-aminolaevulinic acid) from succinyl CoA + glycine).
*not a porphyria
Causes X-linked sideroblastic anaemia
Acute intermittent porphyria
what enzyme is defecient?
HMB synthase (hydroxymethylbilane)
aka
PBG deaminase (porphobilinogen deaminase)
-> buildup of ALA and PBG in serum and urine.
Acute intermittent porphyria
what inheritance?
autosomal dominant
What causes the neurovisceral symptoms in porphyria?
5-ALA
(5-aminolaevulinic acid)
is neurotoxic
what causes the skin lesions in porphyria?
porphyrins.
porphyrinogens become oxidised to porphyrins, which under light become activated porphyrins and oxygen.
porphorinogens are colourless while porphyrins are highly coloured.
also, porphyrinogens get oxidised in the circulation where there is high [O2] compared to in the cells where it is made.
Acute intermittent porphyria
symptoms
Auto dominant inheritance
HMB synthase deficiency
accumulation of PBG and ALA -> neurovisceral attacks
abdo pain, nausea and vomiting, tachycardia, HTN
constipation and urinary incontinence
hypoNa (SIADH)
seizures, psych distrubances
NO cutaneous manifestations
Treatment and Mx of acute intermittent porphyria
Avoid precipitating factors - adequate nutritional intake, avoid precipitant drugs, prompt treatment of infection/ illness
IV Carbohydrate + IV Haem Arginate (key tx)
- inhibits ALA synthase, which turns off the pathway and reduces [ALA]
porphyria cutanea tarda
PCT
presentation
blistering
inherited/ acquired e.g. liver disease/ drugs
formation of vesicles on sun exposed areas of skin crusting, superficial scarring, pigmentation
PCT
porphyria cutanea tarda
which enzyme deficiency?
uroporphyrinogen decarboxylase deficiency
Ix: raised urinary uroporphyrins + coproporphyrins + increased ferritin
mx: avoid precipitants (alcohol, hepatic compromise)
Presentation of homocystinuria?
Marfanoid habitus
Downward lens dislocation
mental retardation
heart rarely affected
recurrent thrombosis
What is homocystinuria
auto recessive
Cystathione B-synthetase deficiency
-> accumulation of homocystine
Mx of homocystinuria?
Some response to high-dose pyridoxine
what is mutated in reticular dysgenesis (autosomal recessive severe SCID)
adenylate kinase 2 (AK2)
- a mitochondrial enzyme metabolism enzyme
mutation in AK2 + low neutrophils, lymphocytes, macrophages, platelets, requiring bone marrow transplantation
reticular dysgenesis
type of SCID
what is mutated in Kostmann syndrome
HAX-1 (HCLS1 associated protein X-1)
severe congenital neutropenia with HAX1 mutation
Kostmann syndrome
Ix of Kostmann Syndrome?
PMN: absent
Adhesion molecules: normal
NBT/DHR: absent
Pus: none
Mx of Kostmann syndrome?
G-CSF or BMT
episodic neutropenia every 4-6 weeks, mutation in ELA2
cyclic neutropenia
what is mutated in cyclic neutropenia
neutrophil elastase ELA-2
what is the inheritance of cyclic neutropenia
autosomal dominant
Mx of Cyclic neutropenia?
G-CSF
recurrent infections, very high neutrophil counts in blood during infection, absence of pus formation, delayed umbilical cord separation.
leukocyte adhesion deficiency
in leukocyte adhesion deficiency, what is the mutation/ deficiency?
CD18 deficiency.
CD11a/DC18 and CD11b/CD18 expressed on neutrophils regulate neutrophil adhesion and transmigration
what receptors are involved in neutrophil adhesion and transmigration?
CD11a/ CD18
CD11b/CD18
what complement proteins are involved in the classically pathway?
C1, C2, C4
what is the main complement protein that is activated by the classical, alternative and lectin pathway?
C3
Ix of Leukocyte Adhesion Deficiency?
PMN increased
Absent Adhesion molecules
Nitroblue Tetrazolium test abnormal/ negative
chronic granulomatous disease
in chronic granulomatous disease, what is deficient?
NADPH oxidase
which complement protein is involved in the alternative pathway?
C3
C3 binds directly to
techoic acid on Gram + bacteria and to LPS on gram - bacteria
+ involves factors B, I, P
Which complement proteins are involved in the lectin pathway?
C2 and C4
mx of chronic granulomatous disease
IFN gamma
dihydrorhodamine flow cytometry test abnormal / negative
chronic granulomatous disease
chronic granulomatous disease presentation
susceptibility to bacteria esp catalase + bacteria.
(ie recurrent pneumonias + abscesses)
granuloma formation + lymphadenopathy + hepatosplenomegaly
chronic granulomatous disease pathology
absent respiratory burst due to deficiency of one of the components of NADPH oxidase.
impaired killing if intracellular microorganisms and excessive inflammation with granuloma formation
Ix of Chronic Granulomatous Disease?
Nitroblue Tetrazolium test abnormal + dihydrorhodamine flow cytometry test abnormal
susceptibility to infection with mycobacteria (TB and atypical), BCG, Salmonella. What condition?
deficiency of IFNgamma/ IL12 and their receptors.
what happens when one is deficient in early classical pathway? ie. C1/2/4
immune complexes fail to activate complement pathway -> increased susceptibility to infection
increased load of self-antigens
deposition of immune complexes which stimulated inflammation in skin, joints, kidneys e.g. SLE
complement deficient - susceptibility to?
encapsulated bacteria
e.g. neisseria meningitidis,
strep pneumoniae, h influenza
IL12/ IFNy
or receptor deficiency
- what organisms are they susceptible to?
Mycobacteria and salmonella
BCG infection after vaccination
No granulomas
what immune cells are vital for protection against viral infections and tumours?
NK cells and CD8 T cells
4 month old, infections of all types, failure to thrive, persistent diarrhoea
SCID
increased infection in patients who have another cause of immune impairment e.g. premature infant, HIV infection, chemotherapy, antibody deficiency
MBL deficiency
DiGeorge’s syndrome
CATCH 22
Cardiac abnormalities (esp Tetralogy of Fallot)
Abnormal facies (low set ears, high forehead)
Thymic aplasia
Cleft palate
HypoCa/ HypoPTH
Chr22- deletion at 22q11.2
Thymic aplasia - reduced numbers of T cells. which condition?
DiGeorge’s
low T cells and NK cells, normal B cells, but low Igs.
X linked SCID
Absent expression of MHC Class II molecules
Bare Lymphocyte Syndrome type II
absent expression of MHC Class I molecules
Bare lymphocyte syndrome type I
Bare lymphocyte Syndrome type II
absent MHC Class II -\> profound deficiency of CD4+ T cells \+ failure to produce IgA/ IgG because no class switching
infections of all types.
may be associated with sclerosing cholangitis
FTT after 3 months
In Bare Lymphocyte Syndrome Type II,
which cell populations are reduced?
CD4
IgG, IgA
tx of digeorge’s syndrome?
Thymus transplant
in DiGeorge’s Syndrome, what cell populations are reduced?
CD4, CD8 T cells
IgG, IgA
mutation in X linked SCID?
IL2R gamma chain mutation
(T cell- but B cells normal + IgM may be normal)
mutation of auto recess SCID?
ADA deficiency
Adenosine Deaminase
-> everything T and B cells are low
Hyper IgM syndrome aka
CD40L deficiency
what gene is defective in Bruton’s X linked hypogammaglobulinaemia
B cell tyrosine kinase gene
(BTK gene)
absence of mature B cells and no circulating Ig. Recurrent infections. Family history where brother is affected.
X linked Bruton’s hypogammaglobulinaemia
recurrent respiratory tract and GI tract infections
selective IgA deficiency
Selective IgA deficiency patients are at risk of what during blood transfusion?
anaphylaxis due to introduction of donor IgA
High IgM, undetectable Ig G, Ig A, Ig E. Normal number circulating B cells.
failure of class switching due to T cell defect.
recurrent infections- e.g. h influenza, strep pneumo, pseudomonas, pneumocystis jiroveci
Hyper IgM syndrome
aka CD40L defciency
what gene is mutated in Hyper IgM syndrome?
CD40 Ligand gene
(CD40L normally on T cell)
Other than HIV, what other condition increases risk of pneumocystis jiroveci infection?
Hyper IgM syndrome
What cell populations are reduced in Brutons hypogammaglobulinaemia?
B cells low
IgM/G/A all low
because pre-B cells cannot mature due to B cell tyrosine kinase deficiency
what cell populations are reduced in Hyper IgM syndrome?
raised IgM
low Ig G/A
due to defective CD40 signalling - B cells cannot undergo class switch recombination and somatic hypermutation
what condition is assoc w selective IgA deficiency?
Coeliac Disease
no germinal centre development within lymph nodes and spleen. No class switching occurring.
Hyper IgM syndrome
after an acute anaphylactic episode, how to confirm via ix?
measure serum mast cell tryptase (should return to baseline by 6h)
first line test for allergy
skin prick (more sensitive and specific than blood tests)
SLE associated with which complement deficiencies?
most common C2
C1q, C1r, C1s, C2 and C4 deficiency all seen in SLE
Ix of Complement Dysfunction?
C3, C4 level
CH50: classical pathway
AP50: alternative pathway
if CH50 and AP50 both abnormal w normal C3/4 = final common pathway deficiency (C5-9)
Presentation of B, I, P deficiency?
deficiency in alternative pathway
increased risk of infection w encapsulated bacteria
- Meningococcus, pneumococcus, H influenzae
FHx of infection
Abnormal AP50
presentation of C5-9 deficiency?
deficiency in terminal pathway -> inability to MAC (membrane attack complex)
increased risk of infection w encapsulated bacteria
- Meningococcus, pneumococcus, H influenzae
FHx of infection
*CH50 and AP50 abnormal w normal C3,4
presentation of common variable immune deficiency?
recurrent bacterial infections:
- bronchiectasis
- sinusitis
usually chronic lung disease + GI infections
Autoimmune disease
Granulomatous disease
What cell populations are decreased in Common variable immune deficiency
Low Ig G and Ig A
cause is poorly understood
Tx usually lifelong Ig replacement therapy
X-linked recessive disease
eczema, thrombocytopenia, immunodeficiency and bloody diarrhoea
Wiskott-Aldrich Syndrome
what gene mutation is implicated in Wiskott-Aldrich?
X-linked
WASP gene mutation
Features of Wiskott-Aldrich Syndrome?
eczema
thrombocytopenia
immunodeficiency
raised Ig E
what immunoglobulins are low/ raised in Wiskott-Aldrich Syndrome?
Ig A and Ig E are raised
Ig M is low
Ig G: may be normal, raised, low
Where is the mutation in X linked SCID?
Mutation of gamma chain of IL2 receptor on chromosome Xq13.1
Very low or absent T and NK cell numbers, Normal or increased B cell numbers but low Igs
X linked SCID
what is deficient in auto recessive SCID?
Adenosine deaminase (ADA) deficiency -\> accumulation of precursors are toxic to lymphocytes.
mx of auto recessive SCID?
PEG-ADA enzyme replacement therapy
how does the IL12-IFNy network usually work?
Infected macrophages produce IL12 -> IL12 induces T cells to produce IFNy -> IFNy stimulates macrophages to produce TNF and activates NADPH oxidase.
B cell differentiation involves which ligands?
CD40-CD40L interaction
site of T cell maturation?
Thymus
site of B cell maturation?
Bone marrow
secondary lymphoid organs?
Spleen, LNs, MALT
brutons agammaglobulinaemia mx?
IVIG
main cytokine responsible for fibrosis seen in CREST syndrome?
TGF-beta.
stimulates collagen production by fibroblasts.
rheumatoid arthritis
how does it affect the complement pathway?
high CH50.
complement factors are acute phase proteins and a high CH50 indicates acute or chronic inflammation.
type 2 autoimmune hepatitis- what autoantibody?
anti-LKM-1.
anti liver/ kidney microsomal-1 antibody
what three sites are classically affected in hereditary angio-oedema?
upper airway, subcutaneous tissues and abdo organs (diarrhoea/ abdo pain).
magnesium deficiency can lead to hypo….?
hypoCa, hypoK, hypoPTH
before a transplant, what medication would you give to induce the patient?
suppress T cell response
e.g. anti-CD25 Basiliximub or anti-CD52 Alemtuzumab or OKT3 (muromonab)/ Anti-thymocyte globulin
calcineurin inhibitor with side effects of nephrotoxicity, neurotoxicity, HTN, dysmorphic features and gum hypertrophy
cyclosporin
calcineurin inhibitor with side effects of nephrotoxicity, neurotoxicity, HTN and is diabetogenic
tacrolimus
what are calcineurin inhibitors indicated in?
transplant rejection prophylaxis by reducing T cell activation and proliferation
calcineurin inhibitors?
tacrolimus and cyclosporin
calcineurin normally activates IL-2. -> calcineurin inhibitors reduce T cell activation and proliferation
what is the most sensitive specific in pernicious anaemia?
anti parietal cells antibody
mixed connective tissue disease
antibody?
anti-U1RNP antibody (speckled pattern)
presentation of hereditary angioedema?
attacks may be precipitated by alcohol, exercise, stress
recurrent angioedema but urticaria + not itchy:
skin
oropharynx -> asphyxia (laryngeal oedema)
GIT - nausea, vomiting, diarrhoea, abdo pain
+ve Family history
Normal C1/3 but low C2 and C4
Hereditary angioedema aka?
C1 esterase deficiency
Diagnosis of Hereditary angioedema?
C1 inhibitor - quantitatively low in type 1 (85%)
C1 inhibitor - functionally deficient in type 1 (15%)
C4 (low)
features of infections in immune deficiency?
2 major or 1 major + recurrent minor infections in 1 year
unusual organisms
unusual sites
unresponsive to oral abx
chronic infections
early structural damage
May be history of anxiety
‘lump in the throat’
Symptoms are often intermittent and relieved by swallowing
Swallowing of saliva is often more difficult.
Usually painless - the presence of pain should warrant further investigation for organic causes
Globus pharyngis (also known as globus hystericus)
liver impairment is possible due to statins.
How often should LFTs be measured?
at baseline, 3 months and 12 months
tx should be discontinued if serum transaminase conc rise to and persist at 3x the Upper limit
The whole colon, without skip lesions, is affected by an irregular mucosa with loss of normal haustral markings.
ulcerative colitis
Barium enema shows:
loss of haustrations
superficial ulceration, ‘pseudopolyps’
long standing disease: colon is narrow and short -‘lead pipe colon’
what does barium enema of Ulcerative colitis show?
loss of haustrations
superficial ulceration, ‘pseudopolyps’
long standing disease: colon is narrow and short -‘lead pipe colon’
apart from antibiotics, what medications increases risk of c difficile infection?
PPI e.g. omeprazole
1st line long term mx of TIA?
Clopidogrel 75 mg daily
2nd: aspirin + modified release dipyridamole if C not tolerated
aspirin if both C and D not tolerated
modified release dipyridamole if C and A not tolerated
immediate antithrombotic tx in TIA?
aspirin 300mg
unless
- pt has a bleeding disorder/ taking anticoag -> immediate admission for imaging to exclude haemorrhage
- pt alr taking low dose aspirin -> cont dose until reviewed by specialist
- aspirin contraindicated
which anti emetic is contraindicated in Parkinson’s disease?
Metoclopramide - dopamine antagonist
used for nausea, GORD
SE: oculogyric crisis, hyperprolactinaemia, tardive dyskinesia, parkinsonism
depigmented Ash leaf spots which flouresce under UV light
Tuberous Sclerosis
Shagreen patches:
roughed patches of skin over lumbar spine
Tuberous sclerosis
adenoma sebaceum (angiofibromas): butterfly distribution over nose
Tuberous Sclerosis
fibromata beneath nails (subungual fibromata)
painless, slow-growing tumor seen in the nail apparatus
-> tuberous sclerosis
neuro features of tuberous sclerosis?
developmental delay
epilepsy (infantile spasms or partial)
intellectual impairment
Teratogenic features of phenytoin?
assoc w cleft palate and congenital heart disease
what AED is assoc w peripheral neuropathy as a side effect?
Phenytoin
if pt is symptomatic (ie polyuria/ polydipsia), what else do you need to diagnose pt w Diabetes Mellitus?
fasting glucose greater than or equal to 7.0 mmol/l (or HbA1c >48mmol)
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
what investigation would be most useful initially to differentiate between irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in primary care?
Faecal calprotectin
released in the bowel in the presence of inflammation
A positive result does not indicate definite IBD but patients should be referred on to secondary care for further investigation.
Ix that should be done for IBS?
FBC, ESR, CRP and coeliac screen (TTG)
Treatment of asymptomatic hyperuricaemia?
none
just conservative
Lifestyle changes (less red meat, alcohol and sugar) can reduce uric acid levels
Ix of Lyme Disease?
Lyme disease can be diagnosed clinically if erythema migrans is present
enzyme-linked immunosorbent assay (ELISA) antibodies to Borrelia burgdorferi are the first-line test
if this test is positive or equivocal then an immunoblot test for Lyme disease should be done
Mx of disseminated Lyme disease?
ceftriaxone
1st line drug in mx of ocular myasthenia gravis?
Pyridostigmine (anticholinesterase)
+/- prednisolone
alternative mx of wilson’s disease?
trientine hydrochloride is an alternative chelating agent which may become first-line treatment in the future
young person w liver and neurological disease?
Wilsons disease
liver: hepatitis, cirrhosis
neurological: basal ganglia degeneration, speech, behavioural and psychiatric problems are often the first manifestations. Also: asterixis, chorea, dementia
tx of choice for smoking cessation in pregnancy?
if smoking cessation without nicotine replacement fails.
nicotine replacement patch
varenicline and bupropion are contraindicated
what is TIBC measuring?
TIBC is a measure of available binding sites on transferrin. If there is a lot of iron, these sites are taken up so there is less capacity to bind more, hence TIBC is low in iron overload.
TIBC high in Fe deficiency
Ix to screen for haemochromatosis?
general population: transferrin saturation is considered the most useful marker.
testing family members: genetic testing for HFE mutation
joint xrays in Haemochromatosis characteristically show?
chondrocalcinosis
features of Orf?
Orf is a viral skin disease spready to humans by handling infected sheep and goats e.g. farmers, sheep shearers, vets
- caused by a parapoxvirus
small, red, itchy or painful lump (lesion) that usually appears on the fingers, hands, forearms or face after an incubation period of 3 to 5 days
lesion -> pustule or blister
+ fever, fatigue, LNpathy
Calcaneal Spur on XR
-> common in plantar fasciitis
If QRISK score is high (>10%), what tx?
Statins indicated
Posterior vs anterior hip dislocation?
90% of hip dislocations are posterior
posterior: limb flexed, adducted, internally rotated
(may be assoc w sciatic n palsy)
Anterior: limb externally rotated w mild flexion and abduction
1st Ix of pancreatic cancer?
Abdo US
what abx medication may cause yellow skin?
Co-amoxiclav
-> may cause cholestatic jaundice
what medication is associated with seeing yellow tinge around lights?
Digoxin assoc w xanthopsia (yellow tinge on white objects)
Mx of stable angina?
GTN sublingual for rapid relief of symptoms
1st line regular tx: BB (bisoprolol, atenolol) or CCB (verapamil)
most likely histological type of renal cell cancer?
clear cell
airway mx of choice if GCS<8?
cuffed endotracheal tube
teratoma/ germ cell tumours
tumour markerS?
AFP
BHCG
what muscle group is overused in medial vs lateral epicondylitis?
medial: flexor compartment
lateral: extensor compartment
what is sildenafil?
used to treat erectile dysfunction and pulmonary hypertension
MOA: phosphodiesterase (PDE5) inhibitor
what vein is compressed in Budd-Chiari?
Hepatic vein thrombosis
e.g. Polycythaemia Rubra vera, Pregnancy
/ compression
what nerve is affected in herpes zoster ophthalmicus?
Trigeminal nerve V1 - ophthalmic branch
e.g.s of non sedating antihistamines?
cetirizine
features of typical angina?
- constricting discomfort in the front of the chest, or in the neck, shoulders, jaw or arms
- precipitated by physical exertion
- relieved by rest or GTN in ~5 minutes
all 3= typical angina
2 = atypical angina
0/1 = non anginal chest pain
Ix of Stable Angina?
1st line: CT coronary angio
2nd: Non-invasive functional imaging
- MPS (myocardial perfusion scintigraphy) w SPECT
- stress echo
- MR imaging
3rd line: invasive coronary angio
High CK and K after giving Abx
what abx?
what condition?
trimethoprim
in CKD
Young pt on chemo, which drug may cause heart failure?
Doxorubicin
worldwide commonest cause of IDA?
Hookworm infection
Mx of SIADH?
fluid restrict
mx of acute exacerbation of COPD who does not require admission?
- Increase doses/ freq of use of SABA
- oral corticosteroids 30mg OD 7-14d if SOB interferes w daily activities
- Oral Abx: amoxicillin, or doxycycline or clarithromycin
abx for acute pyelonephritis?
1st line: cefalexin, or co-amoxiclav or trimpethoprim or cipro
if pregnant: cefalexin
what is Caplan’s syndrome?
rheumatoid arthritis, pneumoconiosis and pulmonary rheumatoid nodules
Anion gap formula?
Na+ + K+- Cl- -HCO3-
usually 10-18
DKA insulin therapy?
fixed rate insulin infusion (0.1u/kg/h) + continue long acting insulin
Mx of Orthostatic hypotension?
education and lifestyle measures such as adequate hydration and salt intake
discontinuation of vasoactive drugs e.g. nitrates, antihypertensives, neuroleptic agents or dopaminergic drugs
if symptoms persist, consider compression garments, fludrocortisone, midodrine, counter-pressure manoeuvres, and head-up tilt sleeping
features of acute liver failure?
hepatic encephalopathy + jaundice + coagulopathy (raised PT time)
+ hypoalbuminaemia
renal failure common (hepatorenal syndrome)
features of Kartagener’s syndrome?
aka primary ciliary dyskinesia
- > immotile cilia
- dextrocardia or complete situs inversus
- bronchiectasis
- recurrent sinusitis
- subfertility (secondary to diminshed sperm motility and defective ciliary action in fallopian tubes)
What type of malignancy is most assoc w Acanthosis nigricans?
GI carcinoma
How much morphine to prescribe a palliative care patient?
to begin: opioid-naive pts can be started on oral morphine, 5-10mg every 4 h.
Once a 24h requirement is established: dose can be given as modified release preparation in 2 divided doses
+ 1/6 of total daily morphine dose should be given PRN for breakthrough pain
ie. if pt needs 60mg,
give 30mg of modified release morphine BD + 10mg total daily dose of morphine for breakthrough pain
mx of dermatitis herpetiformis in coeliac?
tx underlying cause- gluten free food
dapsone can reduce symptoms of itching
mx of pyoderma gangrenosum?
high dose oral prednisolone which are gradually redeuced as lesions heal
+ application of non-adherent dressings
Mx of Lyme Disease assoc w cardiac or neurological complications?
IV ceftriaxone or cefotaxime
1st line ix for Lyme Disease?
ELISA antibodies to Borrelia burgdoferi
what are the preferred opioids in patients with chronic kidney disease.?
Alfentanil, buprenorphine and fentanyl
Mx of cerebral abscess caused by streptococcal or anaerobic infections?
IV cefuroxime and metronidazole
Mx of Cerebral abscess caused by staphylococcal infection?
IV flucloxacillin with cefuroxime
what NOAC is most preferred in pts with CKD?
Apixaban
What is the single most important factor in determining whether cryoprecipitate should be given?
low fibrinogen level
features of legionella?
dry cough
relative bradycardia
lymphopenia
hypoNa
deranged LFTs
pleural effusion
HAART usually involvs?
2 NRTIs
+
protease inhibitor or NNRTI
e.g.s of entry inhibitors
CCR5 receptor antagonists?
maraviroc, enfuvirtide
prevent HIV-1 from entering and infecting immune cells by blocking CCR5 cell-surface receptor
e.g.s of Nucleoside reverse transcriptase inhibitors?
Zidovudine, Abacavir, Lamivudine, Emtricitabine, Tenofovir
e.g.s of NNRTIs?
efavirenz, nevirapine
e.g.s of protease inhibitors?
-navir
indinavir, ritonavir
e.g. of integrase inhibitors
-gravir
Raltegravir, dolutegravir
maintenance fluid requirements for adults based on weight?
25-30ml / kg/ day of water
ie. 80kg patient - 2L of water
fluid requirements of children?
100mL / 24 hr/ kg (0-10kg)
then 50 mL/24h /kg (11-20 kg)
then 20 mL per kg after
1st line tx in MODY
HNF1A type
Sulphonylureas e.g. gliclazides
urea breath test
- what may decrease the accuracy?
No abx in past 4 wks
no PPIs in past 2 wks
preferred method of acces for haemodialysis?
AV fistulas
VTE prophylaxis after elective hip replacement?
LMWH for 28d
or
LMWH for 10d then aspirin for 28d
or
Rivaroxaban
VTE prophylaxis after elective knee surgery?
LMWH for 14d
or
Aspirin for 14 d
or
Rivaroxaban
VTE prophylaxis for fragility fractures of the pelvis, hip and proximal femur?
LMWH or fondaparinux
continue until pt no longer has significantly reduced mobility
SEs of hydroxychloroquine?
bulls eye retinopathy- may result in severe and permanent visual loss
-> baseline opthal examination + monitor annually
allergy to sulfasalazine may also mean allergy to??
aspirin or sulphonamides
abx prophylaxis for meningococcal meningitis?
oral ciprofloxacin
terminal cancer, pt suffering from bowel colic?
add hyoscine butylbromide to syringe driver
terminal ca- what to add to syringe driver to reduce resp secretions?
hyoscine hydrobromide
mx of intractable hiccups in palliative care??
chlorpromazine
or haloperidol/ gabapentin
features of anticholinergic symptoms?
Blind as a bat (dilated pupils)
Red as a beet (vasodilation/flushing)
Hot as a hare (hyperthermia)
Dry as a bone (dry skin)
Mad as a hatter (hallucinations/agitation)
“Bloated as a toad”; ileus, urinary retention
And the heart runs alone (tachycardia)
