Gen Med, ICU and Misc Flashcards
What is a Measurand with regard to biochemical testing?
A specifically defined analyte (=constituent of interest)
How do ion selective electrodes work to assess electrolytes? What are their advantages and disadvantages?
Contain an electrode which measures the potential difference the electrolyte of interest and a reference
Advantage: cheap, quick
Disadvantage: Affected by pH, unable to detect interference
What is the basic principle of chemical assays?
Chemical reaction creates colour change which is detected by spectrophotometry
What is the principle of enzymatic assays?
Quantification of substrate or enzyme by measuring the rate of reaction via colour change
What are the serum indices?
Factors that cause interference on assays, typically lipaemia, haemolysis, icterus and antioxidants
What is the underlying principle of immunoassays?
Detection of antigen via specific antibodies, with labelling of antigen or antibody
What is the principle behind sandwich immunoassays?
Detection of an analyte through the capture antibody and a detection antibody, quantity correlates to intensity of signal
Good for larger analytes as requires 2 immunoreactive sites
What is the principle behind competitive immunoassay?
Samples competes with a labelled analyte for binding to a specific antibody, where quantity inversely correlates to intensity of signal
Good for smaller molecules
What is the principle behind a lateral flow assay?
Sandwich assay for specific antigen, with control line often containing antibody against capture antibody
What is the principle behind immunoturbidimetry/nephelometry?
Aggreagation of antibody labelled microbeads due to the presence of antigen increases the turbidity of a sample, which is detected by scatter of light (nephelometry) or penetrance of light (turbidimetry)
What are the main interferences for immunoassays?
- HAMA (human anti-mouse antibody) - result from “immunisation” due to exposure to animal antigen, administration of animal immunoglobulin
- Heterophile antibodies -non specific antibody interference (associated with RF)
- Biotin - used as binding in assay, outcompetes this
- Structurally similar compounds
- Hook effect - feature of rate of assay reaction, where signal decreases with increasing concentration beyond the maximal point, leading to a lower concentration result being inferred from standard curve
- Free hormone hypothesis - where biological activity of hormone is related to unbound proportion, which is difficult to estimate
Why is vitamin D level often falsely low in pregnancy?
Due to free hormone hypothesis, where stripping of vitamin D from protein in incomplete resulting in falsely low results
What is the principle underlying high performance liquid chromatography?
An analyte can be separated based on its physical characteristics
Used for vitamin A+E, -azole drugs
What is the principle underlying gas chromatography mass spectrometry?
Heating of a sample to form a gas (eluent) that is ionised and separated via magnets bending the path of eluent based on mass and charge
What is the principle behind liquid chromatography tandem mass spectrometry?
Analyte separated based on physical characteristics, the irrelevant compounds removed based on mass/charge ratio and then collided with an inert gas to form daughter ions which are run through a second magnet chamber and selected by ratio of mass to charge
What is harmonisation and standardisation with regard to biochemical testing?
Harmonisaton is the process of achieving uniformity of results so that results from different labs can be compared, whereas standardisation is more focussed on being close to the true value
What is the incidence of chronic wounds in Australia and New Zealand, and their common aetiologies?
At any one time 200,000 Aus and 30,000 NZ
Venous and arterial ulcers, diabetic foot ulcers, skin tears
Over what timeframe will most chronic wounds heal with correct diagnosis and mangement?
12 weeks
What are clinical features of venous leg ulcers?
- champagne bottle appearance of lipodermatosclerosis
- haemosiderosis of surrounding skin
- irregular border, shallow, above malleoli but below knee
- Oedema
- Atrophie blanche: small white areas caused by skin ischaemia
How are venous leg ulcers treated?
- rarely with antibiotics
- Debridement: sharp or blunt, mechanical or with dressing
- protect peri ulcer skin
- Dressing: primary, absorbent layer, compression
- Address factors for wound healing: nutrition, smoking, exercise, venous ablation
What are features of lymphoedema ulcer?
- cobble stone cracks
- Stemmer sign: attempt to pinch and lift skin fold at base of second toe, positive = unable to pinch
How is lymphoedema treated?
- compression
- massage
- weight loss
What are features of arterial ulcers?
- sharp, punched out (deep) ulcers
- distal to ankle
- poor perfusion: poor capillary return, shiny hairless skin
- ABPI < 0.7
When is compression safe for mixed arterial/venous ulcers?
ABPI >0.7
What are the treatments for arterial ulcers?
- antibioitcs
- debridement
- dressings
- compression if ABPI > 0.7
- analgesia
- revascularisation
What are clinical features of diabetic foot ulcers?
- usually distal or planatar foot/toes, or distal ankle where footwear rubs
- charcots foot
- prone to infection
- callus
How are diabetic neuroischaemic ulcers treated?
- debridement except for dry gangrenous
- dressings
- offload
- podiatry
- BSL control
- Agressive treatment of infection and high suspicion for osteomyelitis
What are the categories of skin tears?
Category 1: linear with no tissue loss OR flap with 10% approximation
Category 2: larger but flap present
Category 3: flap completely missing
How are skin tears prevented and managed?
- prevention: moisturisation, avoid trauma, minimise steroid
- treatment: oppose edges, non-adhesive dressing, remove dressings from base of flap
What are features of zoster rash?
- Vesicular rash clustered on erythematous base
- unilateral in sensory dermatome distribution, most common thoracic, also cervical and ophthalmic
- vesicles crust over 7-10 days, full healing over 1 month
How are Zoster rashes treated?
- antivrial
- treat secondary infection
- hydrogel, non adhesive dressing
- vaccination for prevention
What are features of vasculitic ulcers?
- associated with underlying autoimmune condition
- associated rash (palpable purpurae)
- red edge
- non diagnostic biopsy
How are vasculitic ulcers treated?
- immunosuppresion: steroids incl. topical, tacrolimus, anti-TNF mAbs (adalimumab, infliximab)
What are common features of pyoderma gangrenosum?
- peripheral necrotic tissue
- purplish edge
- no rash
- occur anywhere on body
- biopsy non diagnostic
- DO NOT GRAFT: get pathergy = new disease at site of graft
What are treatments of calciphylaxis ulcers?
- sodium thiosulfate to treat nephrocalcinosis
- 10 g IV 3x/week for 12 weeks
- can also be given topically
How is mycobacterium ulcerans managed?
- biopsy with PCR to confirm diagnosis
- Rifampicin/clarithromycin
- initially deteriorates over first 2-4 weeks due to release of lactoferin and inflammatory response
- simple dressing
What is the definition of a pressure injury?
Any lesion caused by unrelieved pressure resulting in damage of underlying tissue
Includes pressure, friction and shear forces
Pressure over what size will cause a pressure injury?
> 30 mmHg over a bony prominence
How are pressure injuries classified?
Stage 1: no blanching hyperaemia
Stage 2: partial thickness ulcer, extending into epidermis and/or dermis = superficial ulcer/abrasion
Stage 3 = tissue loss down to fascia = deep ulcer
Stage 4: tissue loss through muscle, bone or supporting structures such as tendons. May also have sinus tracts
Unstageable = full thickness loss but base is not visible due to slough (needs to be removed UNLESS if dry)
Suspected deep tissue injury: purple/maroon discoloured skin with blistering
How are pressure injuries managed?
- prevention through frequent turning, if bed bound at least every 2 hours
- if chair bound reposition every hour
- padding with pillows or foam wedges
- cleaning (no soap, reduce friction)
- moisturisers
- lifting devices to lift
- pressure relieving devices
- treat at first sign of redness
- nutrition (some evidence for 4.5 -9g arginine per day)
What are the 4 factors of wound bed preparation with regard to wound healing?
TIME
Tissue: debridement to develop a viable wound base
Infection: bacterial balance to control chronic inflammation
Moisture: exudate management (specifically to minimise proteases which delay wound healing)
Edge: promote re-epithelialisation via debridement, skin grafts, biologics
What are the aims for different tissue types when choosing a wound dressing?
Eschar: to remove it unless dry without erythema
Slough: aid autolyic debridement
Granulation tissue: protect + provide moisture management
Epithelium: protect
What is the role in compression in wound management?
Reduces fluid escape from the venous/capillary system to reduce oedema, including through supporting incompetent venous valves and venous return
What are the indications for Ga68-PSMA PET/CT in prostate cancer?
- Elevated PSA without tumour detection
- Initial staging
- detection of recurrence after initial therapy in the setting of rising PSA
- therapy monitoring
What is the significance of PET for cardiac amyloid?
- can identify TTR cardiac amyloid (in conjunction with negative urine and serum amyloid light chains), which informs ability to use tafamidis (presents amyloidogenesis)
What is theranostics with regard to nuclear medicine?
The ability to diagnose a condition and then treat it with high dose radionucleotide
e.g. prostate cancer identified with Ga68-PSMA uptake, the treated with Lu177-PSMA
What is the incidence and common causes of secondary hypertension?
- 5-10% people with elevated BP
- young = renal parenchymal disease, coarctation of the aorta
- > 65 = atherosclerotic renal artery stenosis, CKD, hypothyroidism8
What clinical features suggest a diagnosis of secondary hypertension?
Age < 30
On 3 or more agents
Acute worsening control
What are indicators of a renovascular cause for secondary hypertension?
- increase in serum Cr >50% occurring in 1/52 of initiating ACEi/ARB
- severe hypertension with unilateral smaller kidney or size discrepancy > 1.5 cm
- recurrent flash pulmonary oedema
What is the triad of hyperaldosteronism?
Hypertension, unexplained hypokalaemia, metabolic alkalosis
(note 50-70% patients have normal potassium)
What proportion of patients with phaeochromocytoma have paroxysmal hypertension?
50%
What is the definition of hypertensive urgency and what is recommended management?
SBP >180 or DBP > 110, with symptoms such as headache, moderate non acute end organ damage
Managed with oral medications (small doses of short acting medications, or usual if missed dosed)
What is the definition of a hypertensive emergency and how is it managed?
SBP > 220 or DBP > 140, severe end organ damage such as APO, encephalopathy, neurological symptoms, AKI, aortic dissection, eclampsia
Lower MAP by 20-25% within first 2 hours with rapid acting meds (may need to be faster in haemorrhagic stroke or aortic dissection)
When is pharmacological management indicated for elevated BP?
- if high absolute risk (>15%)
- High BP >160/100
- CKD, TIA/CVA, diabetes, MI, CCF, PAD, elderly
What are lifestyle modifications that can help to manage elevated BP?
- weight
- physical activity
- salt reduction
- diet
- alcohol intake
- smoking cessation
What are recommended first line anti-hypertensives?
ACEi or ARB, CCBs or thiazides
From the REASON study, what factors and complications were associated with increased mortality?
FACTORS:
- increasing age
- higher ASA status
- pre op albumin < 30
- unplanned surgery
COMPLICATIONS:
- renal impairment
- unplanned ICU admissions
- systemic inflammation
What are features of a bundle of care in perioperative medicine?
- clinical pathways
- multi disciplinary involvement
- dedicated ward
- early recognisation of complications
- dedicated champions
What is the definition of high risk surgery?
> 5% risk of mortality
What are the ASA classifications?
Stratification of patients based on disease status, does correlate with outcomes
1- normal healthy patient
2- mild systemic disease (no functional limitation)
3- severe systemic disease (functional limitation)
4- severe systemic disease that is constant threat to life
5- moribound patient who is not expected to survive without an operation
6- declared brain dead for organ removal
What cardiac conditions are high risk and pose as contraindications to non-cardiac surgery?
- ACS
- Acute decompensated HF
- Unstable arrhythmias
- symptomatic severe AS
When is perioperative stress testing indicated?
For patients at elevated risk for non cardiac surgery with poor functional capacity (<4 METs) if the results of stress testing will change management
Stress testing performed as dobutamine stress echo
What are the guidelines for antiplatelets following cardiac stent for non cardiac surgery?
- DAPT for minimum 1/12 after BMS (bare metal stent)
- minimum 3-6 months after DES
- minimum 12 months after ACS
What are the risk factors for post operative respiratory complications?
- increased age
- smoking
- pre existing lung disease
- OSA
- pulmonary hypertension
- heart failure
- duration of anaesthesia
- anaesthetic technique
- neuromuscular blockade type
(not obesity)
What is the role of preoperative pulmonary function tests and CXR?
PFTs indicated for:
- cardiac surgery or lung resection
- investigation of undiagnosed SOB
- assess airways disease control
CXR indicated for undiagnosed dyspnoea, > 50 undergoing high risk surgery and known cardiopulmonary disease
What is the definition of SIRS?
2 or more of:
T > 38 or < 36
HR > 90
RR > 20 or pCO2 < 32
WCC > 12 or > 10% immature band forms
What is the definition of sepsis?
Life-threatening organ dysfunction caused by dysregulated host response to infection
qSOFA 2 or more of:
- SBP < 100
- GCS < 15
- RR > 22
What is the definition of septic shock?
Sepsis despite adequate volume resuscitation and:
- persisting hypotension requiring vasopressors to maintain MAP > 65
- Lactate > 2
How is procalcitonin used to guide antibiotics management?
Indicator of bacterial source of inflammatory response, > 0.5 indicates bacterial infection
If decreasing from baseline and still > 0.5 continue antibiotics
If increasing from baseline and > 0.5 switch antibiotics
If < 0.5 stop antibiotics
How should patients with septic shock be resuscitated?
- broad spectrum antibiotics
- IV fluid at 30 mL/kg, balanced crystalloid initially (avoid albumin in head trauma)
- aim MAP > 65 on arterial measurement
- Blood if Hb < 70
- corticosteroid (hydrocortisone 200 mg)
- source control
What is the 1st line and 2nd line vasopressors for shock with normal cardiac output?
1st line = Noradrenaline or adrenaline (note adrenaline can affect lactate levels)
May use metaraminol until central line established
2nd line = vasopressin
What are the vasopressors used in shock with low cardiac output?
1st line: dobutamine or adrenaline
What are the features of Anticholinergic toxidrome?
Hot = hyperthermia
Dry = sweating
Mad = delirium, psychosis, seizure, coma
Blind = blurred vision
Red = vasodilation
Other: urine retention, tachycardia
What are the features of Cholinergic toxidrome?
CNS: agitation, confusion, seizures
Muscarinic:
Diarrhoea
Urination
Miosis
Bronchospasm
Bronchorrhoea (sputum)
Bradycardia
Emesis
Lacrimation
Salivation
Neuromuscular = fasiculations, muscle weakness, paralysis
What are the features of neuroleptic malignant syndrome?
CNS: confusion, delirium, decreased LOC, coma
ANS: tachycardia, labile BP, dysrrhythmia, hyperthermia, diaphoresis
Neuromuscular: hypertonia, tremor, hyperreflexia
What are the features of opioid intocxication toxidrome?
CNS: decreased mental status, miosis
CV: hypotension (histaminergic)
Resp: respiratory depression
What are the features of serotonin syndrome?
CNS: agitation, delirium
ANS: hypertension, tachycardia, hyperthermia, diaphoresis, vomiting, diarrhoea
Neuromuscular excitation: rigidity LL > UL, hyperreflexia, clonus, mydriasis
What are the features of sympathomimetic toxidrome?
CNS: agitation, hallucinations, paranoia, seizures
ANS: hypertesnion, tachycardia, dysrhythmias, hyperthermia, diaphoresis
Neuromuscular: hyperreflexia, tremor
What are methods for decontamination and enhanced elimination in drug toxicity?
Activated charcoal is preferred method for decontamination, also used for elimination if given in multiple doses
Can eliminate through HD, plasmapheresis, exchange transfusion, urinary alkalinization
What are the antidotes for each of these toxins?
1. Organophosphate
2. CCB, Beta blockers
3. Digoxin
4. Benzodiazepine
5. Cyanide
6. Local anaesthetic toxicity
7. Paracetamol
8. Opioids
9. Tricyclics, aspirin
- Atropine
- Calcium
- Digibind
- Flumenazil
- Hydroxycobalamin
- Intralipid
- Paracetamol
- naloxone
- sodium bicarbonate
How is the relative risk calculated?
RR = Risk(treatment)/Risk(control)
Where risk = N(outcome)/total N of that trial arm
e.g RR = (a/(a+b))/(c/(c+d))
How is the risk difference calculated?
RD = Risk(control) - Risk(treatment)
Where risk = N(outcome)/total N of that trial arm
e.g RD = (c/(c+d)) - (a/(a+b))
How is the odds ratio calculated?
OR = Odds(treatment)/Odds(control)
Where Odds for a given arm = N(with outcome)/N(without outcome)
What statistical tests are used for binary data?
Chi-square test to test for an association between event and group
Logistic regression for adjusted analyses
How are continuous data summarised?
Mean and standard deviation
OR
Median and interquartile range
How are continuous data compared?
Difference in mean or difference in medians
How are differences in continuous data tested?
T-test (comparing population means between groups)
Adjusted analyses using linear regression
What is time to event data, how is it summarised, compared and what are appropriate statistical tests?
Time from starting point, such as disease diagnosis or exposure, to the occurrence of an event of interest
Summarised for a group as median time to event (i.e. timepoint at which 50% of group have had event of interest)
Comparisons between groups made using hazard ratio
Statistical test = log-rank test, proportional hazards regression
How is the hazard ratio calculated?
HR = treatment hazard rate/placebo hazard rate
What are the four possible explanations for a difference to be observed between groups?
Bias
Error
Chance (random variation)
True difference
How are bias and error controlled during a scientific study?
Through study design, randomisation, blinding, auditing, validating
How is the effect of chance in a scientific study controlled for?
Statistical analyses
What does a 95% confidence interval measure?
A range of plausible values for a summary measure in which 95% of repeated studies will cover the true value of a summary measure
What is the null hypothesis?
The assumption that the rate of outcome is the same between groups
What does a p-value indicate?
The strength of evidence in a study that a difference between two groups is not the result of chance
IS NOT the significance level
What is Type I (alpha) error? What influences it?
A false positive conclusion
Alpha error = 0.05 (level of statistical significance you set = p-value), where <5% chance of null hypothesis being true
Influenced by chance
Type I error can be reduced by setting a lower statistical significance cut-off (p-value)
What is type II (beta) error?
A false negative conclusion
Beta error = acceptable false negative conclusion
Statistical power = 1- beta, usually> 80% to detect a specified effect size
Influences:
- Inversely proportional to statistical power (determined by sample size)
- proportional to effect size
- Measurement error
- inversely proportional to statistical significance cut-off (p-value)
Are statistically significant events always clinically significant?
No
What is the sensitivity of a test and how is it calculated?
The proportion of true positives for a given test, low sensitivity indicates high false negatives
Sensitivity = true positives/total positive tests
What is specificity and how is it calcualted?
The proportion of true negatives for a given test, low specificity indicates high false positives
Specificity = true negatives/total negative tests
What is positive predictive value and how is it calculated?
The probability a person with a positive test has a disease
PPV = sensitivity x prevalence
———————————–
sens. x prevalence + (1-spec.) x (1 - prevalence)
What is negative predictive value and how is it calculated?
The probability a person with a negative test does not have the disease
NPV = Specificity x (1 - prevalence)
—————————————–
(1 - sens.) x prevalence + spec. x (1 - prevalence)
What influences the PPV and NPV?
Sensitivity and specificity of a test
Prevalence of disease in the population the test is applied to
Higher prevalence = lower NPV but higher PPV and vice versa
What is the traditional hierachy of epidemiological study designs from highest quality data to lowest?
Systematic review (secondary research)
RCT (primary research: interventional)
Cohort study (primary research: observational)
Case-control study (primary research: observational)
Cross sectional study (primary research: observational)
Case report or series (anecdotal)
Commentary (anecdotal)
What are the study design, strengths and weaknesses of a cross-sectional study?
Survey of participants at a single point in time to assess exposure and outcome
Strength: convenience
Weaknesses:
- taken at single point in time so cannot establish temporal association
- risk of confounding due to lack of control of other participant characteristics
What are the study design, strengths and limitations of case-control studies?
Participants selected on outcome and exposure assessed retrospectively
Strengths:
- longitudinal information (can verify temporal association)
- inexpensive
- efficient for rare outcomes
Weaknesses:
- assumes well-defined study base (cases and controls from same source population)
- risk of recall bias = measurement bias where cases more likely to recall exposure than controls
What are the study design, strengths and limitations of cohort studies?
Patients are selected based on exposure and then outcome assessed
Either retrospective or prospective
Strengths:
- longitudinal information to inform temporality
- efficient for rare exposures
Limitations:
- expensive
- risk of selection bias due to characteristics of participants who choose to participate, or variation between exposed and unexposed groups
- vulnerable to loss to follow up
What are the study design, strengths and limitations of randomised control trials?
Participants selected and randomly assigned to an exposure and outcome assessed
Variables are controlled so exposure is only difference between groups
Strengths:
- randomisation controls for known and unknown confounders
- allows assessment of causality
Weaknesses:
- expensive
- needs clinical equipoise
- unfeasible for rare disease
What are the study design, strengths and limitations of ecology studies?
Study of a group rather than an individual
Strengths: convenience
Weaknesses: cannot determine if individuals with exposure are the same individuals with the outcome
What are the phases of clinical trial design?
- preclinical: laboratory based
- Phase I: assessment of safety and dosing
- Phase II: assessment of drug activity and safety
- Phase III: assessment of efficacy and safety
- Phase IV: assessment in real world population (pharmacovigilence)
What are strengths and limitations of the cross over clinical trial design?
Strength: efficiency as each participant acts as their own control
Weaknesses:
- risk of carryover effect from late onset drug effects
- risk of period effects such as underlying disease trajectory over time
What is a factorial clinical trial design?
Where participants are randomised twice for. total of four treatment arms
Allows two questions to be answered simultaneously, but may be subject to biases from interaction between questions
What are platform trials?
Trials with a master protocol with adaptive elements e.g. discontinuing an arm due to lack of treatment effect
What are features of umbrella design, basket design and seamless trials?
Umbrella design: study multiple biomarkers and drugs in a common disease
Basket design: study common biomarkers and drugs in multiple diseases
Seamless trials: combine two or more phases into one adaptive study based on pre-determined interim analyses
What is the difference between blinding and concealment?
Allocation concealment = what happens at time of randomisation to avoid selective enrolment of participants e.g. computer randomisation, sealed envelopes
Blinding = what happens after randomisation to avoid bias in measurement of outcome
What is stratified randomisation?
Randomisation between groups as well as in within key strata e.g. age or country
What are intention to treat analyses and what effect do they have on analysis outcome?
Data analysed according to treatment participant was randomised to regardless of adherence
Preserves the balance of confounders
Underestimates effect of treatment
What are per protocol analyses and what effect do they have on analysis outcome?
Data analysis based on treatment participant actually receives
Can introduce confounders and result in under or over estimation of an outcome
Purpose is to validate findings of intention-to treat analysis
What is a confounder?
A factor that is unevenly distributed between treatment groups that independently affects outcome
What is selection bias and how can it be controlled?
A systematic difference between treatment groups. Informed by comparing group characteristics and loss to follow up
Controlled through randomisation
What is measurement bias and how can it be controlled?
A systematic difference in the measurement of endpoints.
Blinding, standardisation of measurement
What is the difference between precision (reliability) and accuracy (validity)?
Precision = same result produced repeatedly, where results correlate and are in agreement
Accuracy = where result reflects true result
What are the anatomical structures involved in the perception of pain?
Sensed by Adelta and C fibres which synapse in dorsal horn
Then carried by spinothalamic pathway
- dull in paleospinothalamic
- sharp in neospinothalamic
Then up to somatosensory core
Receive modualtion from thalamus
What is the ration of background opioid to breakthrough?
PRN is 1/6th of background except for methadone
What is the conversion ratio of oxycodone and hydromorphone to morphine?
Oxycodone is 1.5x potent than morphine
Hydromorphone is 5x more potent than morphine
What are key considerations with methadone prescription?
Causes QTc prolongation
Metabolised by CYP450:
- inducers cause decreased drug levels (anticonvulsants, rifampicin)
- inhibitors cause increased drug levels (azoles, fluoxetine)
How do you convert oral morphine to subcut morphine?
Divide by 3
What is malignant SVCO syndrome and what cancers is it commonly associated with?
Direct invasion or external compression of the SVC by a tumour that leads to thrombosis within the SVC
50% seen in NSCLC
30% SCLC
15% Non-hodgkins lymphoma
60% SVCO are in patients prior to cancer diagnosis, 10% SCLC present with SVCO
What are clinical features of SVCO and the grades?
Face, neck or arm swelling
Chest pain
Dyspnoea, stridor, cough or hoarse voice
Cerebral oedema - headache
Grade I: incidental
Grade II: symptomatic
Grade III: severe symptoms
Grade IV: life threatening
Grade V: death
How should SVCO be managed?
Diagnosed on CT with contrast
Glucocorticoids (dex) to reduce swelling
Recanalisation and stenting
Radiation therapy (risk of complete SVC obstruction due to swelling, needs dex cover)
Chemotherapy for underlying malignancy
What are common cause of malignant spinal cord compression?
Prostate cancer
Breast cancer
Lung cancer
Multiple myeloma
What are key features of malignant spinal cord compression?
- New progressive severe back pain esp thoracic, worse on coughing, straining or lying flat
- New motor deficit
- Bowel or bladder disturbance (late sign)
How should malignant spinal cord compression be managed?
MRI whole spine, CT myelography if patient unable to under go MRI
High dose dexamethasone (16 mg OD) started when suspected
Pain control
IDC
Laxatives
Surgical decompression and spine stabilisation or external beam radiotherapy
What cancers are the most common cause of catastrophic bleeding? What are other high risk cancers?
Head and neck advanced cancer (5% of cases)
Central lung cancers
Cancers with thrombocytopenia
Cancers with liver disease
How are catastrophic bleeds managed?
- reassurance for patient and family
- positioning of patient for comfort
- midazolam 10 mg for sedation (may need to be higher if already on benzos)
- consider opioid
What cancers are associated with major airway obstruction?
- lung cancers
- laryngeal and nasopharyngeal carcinoma
- oesophageal carcinoma
- mediastinal tumours
How should major airway obstruction be managed?
CT chest once stabilised
Bronchoscopy and stenting if appropriate
External beam radiation as appropriate
Dexamethasone
Opioids and benzodiazepines for comfort
What are common causes of malignant hypercalcaemia?
-80% caused by PTHrP (many cancers)
- Osteolysis (breast, MM, lymphoma, leukaemia)
-1,25DihydroxyVitD: lymphoma, ovarian germinomas
- Ectopic PTH: ovarian, lung, NET, thyroid papillary, pancreatic)
How should malignant hypercalcaemia be managed?
Serial measurements of CCa
PTH, PTHrP, Vit D levels
Bisphosphonate IV
Normal saline +/- IV frusemide
Denosumab in patients who cannot have bisphosphonate esp renal impairment
What is the association between pre pregnancy creatinine and adverse outcomes in pregnancy?
Higher the creatinine the greater the chance of adverse effects:
- pre eclampsia
- pre term delivery
- SGA
- NICU admission
- 25% reduction in eGFR post partum
What is the association between CKD stage and likelihood of complicated pregnancy?
CKD 1-2: likely uncomplicated
CKD 3: likely complicated by CKD progression, pre term delivery at 34-36 weeks, 50% have pre-eclampsia
CKD 4: very likely to be complicated with CKD progression, pre term delivery at 34 weeks, 70-80% pre-eclampsia
What is the most dangerous glomerulonephritis in pregnancy?
SLE
What is the significance of maternal SSA/SSB (Ro/La) in pregnancy?
Fetal heart block (need to be on hydroxychloroquine)
When is the best time to plan a pregnancy in CKD?
Stable kidney function
BP well-controlled
On pregnancy safe medications
Underlying disease (SLE) well-controlled
What happens to serum creatinine in pregnancy?
Reduces EXCEPT in 3rd trimester when begins to rise
What findings in pregnancy suggest an underlying kidney disease?
- impaired renal function including “AKI”
- new proteinuria with PCR > 30 (proteinuria > 300 mg/day) before 20/40
- nephrotic syndrome
- synpharyngitic macroscopic haematuria = IgA nephropathy
Is RAAS blockade contraindicated in pregnancy?
Yes - is teratogenic
What is the target BP in pregnancy and what medications are safe for hypertension?
Target BP < 140/90 and continue unless BP < 110/70
Nifedipine, methyldopa, labetalol, hydralazine
When should aspirin be given in pregnancy?
For prevention of pre-eclampsia in women who are high risk
100-150 mg OD from 10-14/40 until 10 days before delivery
How can pre eclampsia be diagnosed in women with CKD?
Worsening renal function, proteinuria and hypertension can be signs of disease progression
Need to assess platelets, LDH, LFTs, placenta and fetal growth
Role of biomarkers: sFLT1 = anti-aniogenic ratio to PlGF = pro-angiogenic, pre-eclampsia associated with ratio > 38
What is the diagnostic criteria of pre-eclampsia?
Hypertension (BP > 140/90) arising after 20/40 accompanied by:
- Thrombocytopenia < 100
- Cr >88 or doubled from baseline
- elevated transaminases
- headache, confusion or visual symptoms
- haemolysis
- foetal growth restriction
- Proteinuria (NOT essenital)
How is proteinuria in pregnancy defined and what is its significance?
> 300 mg protein in 24 hour urine
OR
Urine Protien:Cr ratio >30
OR
Urine albumin:CR ratio >8
Before 20 weeks = underlying renal disease
After 20 weeks and hypertensive = at risk of pre-eclampsia
After 20 weeks and normotensive = new onset renal disease including autoimmune disease
What is the only definitive treatment of pre-eclampsia?
Delivery of the placenta
What changes to thyroid hormone occur in pregnancy?
50% increase in thyroid hormone synthesis (only T4 can cross placenta)
What are the most common thyroid pathologies in pregnancy?
Subclinical hypothyroidism
Subclinical hyperthyroidism
HCG-mediated hyperthyroidism
Thyroid nodules
What changes happen to TSH in pregnancy?
- decreases in 1st trimester as HCG stimulates thyroid hormone synthesis
- the same in trimester 2 and 3
How should hypothyroidism be managed in pregnancy?
- iodine supplement 150 micrograms OD
- TSH > 10 with decreased T4 should receive replacement
- there is no role in treating or screening for anti-TPO antibodies in pregnancy
How should Graves disease be managed in pregnancy?
PTU = 1st line
The can continue throughout or switch to carbimazole at 16/40 noting PU risk of maternal hepatotoxicity and carbimazole risk of maternal and foetal hypothyroidism
What physiological changes occur in the liver in pregnancy?
- increased liver metabolism
- reduced serum albumin
- Increased ALP (placental produced)
What are characteristics of pregnancy-associated liver disease?
Arise in 3rd trimester and resolves post partum
What are causes of liver disease in pregnancy?
- hyperemesis gravidarum
- intrahepatic cholestasis of pregnancy
- acute fatty liver of pregnancy
- Pre eclampsia/HELLP
