Clinical Science Flashcards
Features of congenital rubella
Classical
- > Sensorineural deafness
- > Congenital cataracts
- > Congenital heart disease (e.g. PDA)
- > Glaucoma
Other
- > Growth retardation
- > Hepatosplenomegaly
- > Purpuric skin lesions
- > ‘Salt and pepper’ chorioretinitis
- > Microphthalmia
- > Cerebral palsy
Features of congenital toxoplasmosis
Classical
- > Cerebral calcification
- > Chorioretinitis
- > Hydrocephalus
Other
- > Anaemia
- > Hepatosplenomegaly
- > Cerebral palsy
Features of congenital cytomegalovirus
Most common congenital infection in UK. Mother asymptomatic.
Classical
- > Growth retardation
- > Purpuric skin lesions
Other
- > Sensorineural deafness
- > Encephalitis/seizures
- > Pneumonitis
- > Hepatosplenomegaly
- > Anaemia
- > Jaundice
- > Cerebral palsy
Definition of confidence interval
A range of values within which the true effect of intervention is likely to lie.
Eg. a confidence interval at the 95% confidence level means that the confidence interval should contain the true effect of intervention 95% of the time
How to calculate 95% confidence interval
Lower limit = Mean - (1.96 x SD)
Upper limit = Mean + (1.96 x SD)
- For 90% use 1.645 *
- If n<100, check Student T test critical value table instead on 1.96)
Definition of standard error of the mean (SEM)
Measure of the spread expected for the mean of the observations
Ie. how ‘accurate’ the calculated sample mean is from the true population mean
How to calculate SEM
SEM = Standard deviation/ Square root (sample size)
=> SEM gets smaller as sample size gets bigger
When to use Students T- test
Parametric data.
Paired -> Data observed from a single group eg. measurements before and after an intervention
Unpaired -> Data observed from 2 separate groups eg. comparing an intervention in 2 different groups.
When to use Pearson’s product-moment coefficient
Parametric correlated data
When to use Mann-Whitney U test
Non-parametric unpaired data.
When to use Wilcoxon signed rank test
Non parametric data. Compares 2 sets of observations on a single sample
When to use chi-squared test
Non parametric data. Used to compare percentages and proportions
When to use spearman, Kendal rank
Non-parametric correlated data
What is pre-test probability?
The proportion of people with the target disorder in the population at risk at a specific time (point prevalence) or time interval (period prevalence)
What is post-test probability?
The proportion of patients with that particular test result who have the target disorder
Post-test probability = post test odds / (1 + post-test odds)
What is the pre-test odds?
The odds that the patient has the target disorder before the test is carried out
Pre-test odds = pre-test probability / (1 - pre-test probability)
What is the post-test odds?
The odds that the patient has the target disorder after the test is carried out
Post-test odds = pre-test odds x likelihood ratio
where the likelihood ratio for a positive test result = sensitivity / (1 - specificity)
Flying recommendations: unstable angina, uncontrolled hypertension, severe valvular disease, uncontrolled arrhythmia, decompensated heart failure
Should not fly
Flying recommendations: uncomplicated MI
After 7-10 days
Flying recommendations: complicated MI
After 4-6 wks
Flying recommendations: coronary artery bypass
After 10-14 days
Flying recommendations: PCI
After 5 days
Flying recommendations: pneumonia
Should be clinically improving with no residual infection
Flying recommendations: pneumothorax
Absolute contraindication.
CAA -> 2 weeks for drainage with no residual air
BTS -> 6 wk post pneumothorax/1wk post check XR
Flying recommendations: pregnancy
Allowed up to 36 wk for single pregnancy
Allowed up to 32 wk for multiple pregnancy
Often need certificate after 28 wk to say pregnancy progressing normally
Flying recommendations: abdominal surgery
After 10 days
Flying recommendations: laproscopic surgery
After 24hr
Flying recommendations: colonoscopy
After 24 hr
Flying recommendations: following application of plaster cast
After 24hr if <2hr flight
After 48hr if >2hr flight
Flying recommendations: haematological conditions
Hb > 80
Inheritance of haemophilla A
X-linked recessive
S&S Cushings reflex
Hypertension (s) then bradycardia (ps)
Physiological reflex to raised ICP
What produces IFN-alpha
Leukocytes
What produces IFN-beta
Fibroblasts
What produces IFN-gamma?
T cells & NK cells
Action of IFN-alpha
Antiviral. Acts on type 1 receptors
Action of IFN-beta
Antiviral. Acts on type 1 receptors
Action of IFN-gamma
Weaker antiviral. More of a role in immunomodulation and in particular macrophage activation. Acts on type 2 receptors
Uses of IFN-alpha
Useful in hepatitis B & C, Kaposi’s sarcoma, metastatic renal cell cancer, hairy cell leukaemia
Uses of IFN-beta
Reduces frequency of exacerbations of relapsing-remitting MS
Uses of IFN-gamma
May be useful in chronic granulomatous disease and osteopetrosis
Side effects of IFN-alpha
Flu-like symptoms & depression
Autosomal recessive conditions
Metabolic conditions except INCLUDES inherited ataxias & EXCLUDES Hunters & G6DP deficiency (X-linked) and hyperlipidaemia type II & hypokalaemia periodic paralysis (AD)
The following conditions are autosomal recessive: Albinism Ataxic telangiectasia Congenital adrenal hyperplasia Cystic fibrosis Cystinuria Familial Mediterranean Fever Fanconi anaemia Friedreich's ataxia ?? Gilbert's syndrome ?? Glycogen storage disease Haemochromatosis Homocystinuria Lipid storage disease: Tay-Sach's, Gaucher, Niemann-Pick Mucopolysaccharidoses: Hurler's PKU Sickle cell anaemia Thalassaemias Wilson's disease
Cause of Turners syndrome
Caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes.
Denoted as 45,XO or 45,X
Features Turners syndrome
Short stature
Shield chest, widely spaced nipples
Webbed neck
Bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
Primary amenorrhoea
Cystic hygroma (often diagnosed prenatally)
High-arched palate
Short fourth metacarpal
Multiple pigmented naevi
Lymphoedema in neonates (especially feet)
Gonadotrophin levels will be elevated
There is also an increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn’s disease
What is Fabry (Anderson-Fabry) disease?
X-linked recessive condition
Deficiency of alpha-galactosidase A
Characterised by abnormal deposits of a particular fatty substance called globotriaosylceramide in blood vessel walls throughout the body.
Features of Fabry disease
Limb pain Sensory neuropathy Raynaud's disease Cardiac arrhythmias, cardiomyopathy Nephrotic syndrome Dermatological manifestation; angiokeratomas, Anhidrosis, cornea verticillate Burning pain/paraesthesia in childhood Angiokeratomas Lens opacities Proteinuria Early cardiovascular disease
What is sensitivity?
Proportion of patients with the condition who have a positive test result
TP/(TP+FN)
What is specificity?
Proportion of patients without the condition who have a negative test result
TN/(TN+FP)
What is positive predictive value?
The chance that the patient has the condition if the diagnostic test is positive
TP/(TP+FP)
What is negative predictive value?
The chance that the patient does not have the condition if the diagnostic test is negative
TN/(TN+FN)
What is likelihood ratio for a positive test result?
How much the odds of the disease increase when a test is positive
sensitivity / (1 - specificity)
What is likelihood ratio for a negative test result?
How much the odds of the disease decrease when a test is negative
(1 - sensitivity) / specificity
Properties of normal population
Symmetrical i.e. Mean = mode = median
- 3% of values lie within 1 SD of the mean
- 4% of values lie within 2 SD of the mean
- 7% of values lie within 3 SD of the mean
What is homocystinuria
Rare AR disease caused by deficiency of cystathionine beta synthase. This results in an accumulation of homocysteine which is then oxidized to homocystine
Features of homocystinuria
Often patients have fine, fair hair
Musculoskeletal: may be similar to Marfan’s - arachnodactyly etc
Neurological patients may have learning difficulties, seizures
Ocular: downwards (inferonasal) dislocation of lens
Increased risk of arterial and venous thromboembolism
Also malar flush, livedo reticularis
How to diagnose homocystinuria
Cyanide-nitroprusside test (which is also positive in cystinuria)
Treatment of homocystinuria
Vitamin B6 (pyridoxine) supplements
Source, stimulus & action of Gastrin
Source -> G cells in antrum of stomach
Stimulus -> Distension of stomach, vagus nerve, intraluminal peptides/amino acids
Inhibited by -> Low antral pH, somatostatin
Action -> Increase HCL, pepsinogen and IF secretion, increases gastric motility, stimulates parietal cell maturation
Source, stimulus & action of CCK
Source -> I cells in upper small intestine
Stimulus -> Partially digested protein and triglycerides
Action -> Increases secretion of enzyme-rich fluid from pancreas, contraction of gallbladder and relaxation of sphincter of Oddi, decreases gastric emptying, trophic effect on pancreatic acinar cells, induces satiety
Source, stimulus & action of Secretin
Source -> S cells in upper small intestine
Stimulus -> Acidic chime, fatty acids
Action -> Increases secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, decreases gastric acid secretion, trophic effect on pancreatic acinar cells
Source, stimulus & action of VIP
Source - > Pancreas, small intestine
Stimulus -> Neural
Action -> Stimulates secretion by pancreas and intestines, inhibits acid secretion
Source, stimulus & action of Somatostatin
Source -> D cells in the stomach & pancreas
Stimulus -> Fat, bile salts and glucose in the intestinal lumen
Action -> Decreases acid and pepsin secretion, decreases gastrin secretion, decreases pancreatic enzyme secretion, decreases insulin and glucagon secretion
inhibits trophic effects of gastrin, stimulates gastric mucous production
Kearns-Sayre syndrome
Mitochondrial inheritance
Onset < 20-years-old
Presentation -> External ophthalmoplegia, Retinitis pigmentosa Ptosis may be seen
Rules of mitochondrial inheritance
Inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
All children of affected males will not inherit the disease
All children of affected females will inherit it
Generally encode rare neurological diseases
Poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy)
Examples of mitochondrial inheritance
Examples include:
-> Leber’s optic atrophy
-> MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
-> MERRF syndrome: myoclonus epilepsy with ragged-red fibres
-> Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa.
Ptosis may be seen
-> Sensorineural hearing loss
cAMP system
Neurotransmitter ligands (receptors)
- > Epinephrine (α2, β1, β2)
- > Acetylcholine (M2)
Hormonal ligands
-> ACTH, ADH, calcitonin, FSH, glucagon, hCG,LH, MSH, PTH, TSH, GHRH*
Primary effector
-> Adenylyl cyclase
Secondary messenger
-> cAMP (cyclic adenosine monophosphate)
Phosphoinositol system
Neurotransmitter ligands (receptors)
- > Epinephrine (α1)
- > Acetylcholine (M1, M3)
Hormonal ligands
-> angiotensin II, GnRH, GHRH*, Oxytocin, TRH
Primary effector
-> Phospholipase C
Secondary messenger
-> IP3 (inositol 1,4,5 trisphosphate) and DAG (Diacylglycerol)
cGMP system
Hormonal ligands
-> ANP, Nitric oxide
Primary effector
-> Guanylate cyclase
Secondary messenger
-> cGMP
Tyrosine kinase system
Hormonal ligands
-> Insulin, growth hormone, IGF, PDGF
Primary effector
-> Receptor tyrosine kinase
Secondary messenger
-> Protein phosphatase
X-linked dominant conditions
The following conditions are inherited in a X-linked dominant fashion*:
- > Alport’s syndrome (in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing)
- > Rett syndrome
- > Vitamin D resistant rickets
What chromosome is p53 on?
Chromosome 17
Cause of Li-Fraumeni syndrome
p53 mutation
What does p53 mutation cause?
Li-Fraumeni syndrome
Most commonly mutated gene in breast, colon and lung cancer
What is p53?
Tumour suppressor gene on chromosome 17
Thought to play a crucial role in the cell cycle, preventing entry into the S phase until DNA has been checked and repaired. It may also be a key regulator of apoptosis
Role of RER
Translation and folding of new proteins
Manufacture of lysosomal enzymes
Site of N-linked glycosylation
Role of SER
Steroid and lipid synthesis
Role of Golgi apparatus
Modifies, sorts and packages molecules destined for cell secretion
Role of mitochondria
Aerobic respiration
Role of nucleus
DNA maintanence
RNA transcription
Role of lysosome
Breakdown of large molecules such as proteins and polysaccharides
Role of nucleolus
Ribosome production
Role of ribosome
Translation of RNA to proteins
Role of peroxisome
Catabolism of very long chain fatty acids and amino acids. Results in formation of hydrogen peroxide
Role of proteosome
Involved in degradation of proteins tagged with ubiquitin
p53 association
Many cancers esp. breat, lung, colon
Li-Fraumeni syndrome
APC association
Colon cancer
BRCA 1+2 association
Breast and ovarian cancer
NF1 association
Neurofibromatosis
Rb association
Retinoblastoma
WT1 association
Wilms tumour
MTS-1 association
Melonaoma
HLA-A3 association
Haemochromatosis
HLA-B5 association
Bechets disease
HLA-B27 association
Ank spond
Reiters syndrome
Acute anterior uveitis
HLA-DQ2/8 association
Coeliac
HLA-DR2 association
Nacroplepsy
Goodpastures
HLA-DR3 association
Dermatitis herpetiformis
Sjogrens syndrome
PBC
HLA-DR4 association
T1DM
RA
Events during G0
“Resting” phase. Hepatocytes & neurons here.
Events during G1
Cells increase in size. Determines length of cell cycle.
Events during S
Synthesis of DNA, RNA & histone. Centrosome duplication
Events during G2
Cells continue to increase in size
Events during M
Mitosis
What is mitosis
Process by which somatic cells divide and replicate. Results in 2 diploid daughter cells.
What is meiosis
Process by which gametes are formed.
Results in 4 haploid cells
Stages of mitosis
Prometaphase -> Metaphase -> Anaphase -> Telophase -> Cytokinesis
Examples of trinucleoside repeat conditions
Fragile X (CGG) Huntingtons (CAG) Myotonic dystrophy (CTG) Freidrichs ataxia (GAA) Spinocerebellar ataxis Spinobulbar muscular atrophy
Trinucleotide repeat responsible for Fragile X
CGG
Trinucleotide repeat responsible for Huntington’s
CAG
Trinucleotide repeat responsible for myotonic dystrophy
CTG
Trinucleotide repeat responsible for Freidrich’s ataxia
GAA
Aim of phase I clinical trial
Determines pharmacokinetics, pharmacodynamics and side effects prior to larger studies.
Conducted on healthy volunteers
Aim of phase IIA clinical trial
Assesses optimal dosage
Aim of phase IIB clinical trial
Assesses efficacy
Aim of phase III clinical trial
Assesses effectiveness
Aim of phase IV clinical trial
Post-marketing monitoring of long-term efficacy and side effects.
Outcome of cohort study
Relative risk
Outcome of case-control study
Odds ratio
What is cohort study
Observational and prospective
What is a case-control study
Observational and retrospective
Characteristics of normal distribution
Mean = median = mode
Characteristics of positively skewed distribution
Mean > median > mode
Characteristics of negatively skewed distribution
Mean < median < mode
What is a funnel plot
Used to demonstrate the existence of publication bias in meta-analyses.
Funnel plots are usually drawn with treatment effects on the horizontal axis and study size on the vertical axis.
What does a symmetrical funnel plot mean
Publication bias unlikely
What does an asymmetrical funnel plot mean
There is a relationship between treatment effect and sample size
Acute phase proteins include
CRP Procalcitonin Ferritin Fibrinogen Alpha-1-antitrypsin Ceruloplasmin Serum amyloid A Serum amyloid P Haptoglobin Complement
Proteins which reduce in the acute phase response are
Albumin Transthyretin Transferrin Retinol binding protein Cortisol binding protein
Definition of incidence
The number of new cases per population in a given time period
Definition of prevalence
The total number of cases per population at a particular point in time
C1 - Inhibitor deficiency
Causes hereditary angioedema
C1q, C1rs, C2, C4 deficiency
Predisposes to immune complex disease such as SLE, Henoch-Schonlein purpura
C3 deficiency
Causes recurrent bacterial infection
C5 deficiency
Predispose to Leiner disease which causes recurrent diarrhoea, wasting and seborrheic dermatitis
C5 - 9 deficiency
Prone to Neisseria meningitis
Which complement deficiency causes hereditary angioedema?
C1 - inhibitor deficiency
Which complement deficiency predisposes to immune complex disease?
C1q, C1rs, C2, C4
Which complement deficiency predisposes to recurrent bacterial infection?
C3
Which complement deficiency predisposes to Leiner disease?
C5
S+S Leiner disease
C5 deficiency. Causes recurrent diarrhoea, wasting and seborrheic dermatitis
What complement deficiency predisposes to Neisseria meningitis?
C5-9
