clinical sci Flashcards
what is the equation for systemic vascular resistance?
Systemic vascular resistance = mean arterial pressure / cardiac output
what is meant by numbers needed to treat (NNT)?
a measure that indicates how many patients would require an intervention to reduce the expected number of outcomes by one
calculated by 1/(Absolute risk reduction)
e.g. control group 4%, test group 2% risk
0.04-0.02 = absolute risk reduction
1/0.02 = 50 = NNT
what is the EER and CER in a study?
Experimental event rate (EER) = (Number who had particular outcome with the intervention) / (Total number who had the intervention)
Control event rate (CER) = (Number who had particular outcome with the control/ (Total number who had the control)
how is relative risk calculated?
relative risk = ratio of contol to test group
e.g 100 patient take control and test drug. of control 50 develop disease, of tes 30 develop disease
relative risk = 03/0.5 = 0.6
if <1 then test drug works
what is relative risk reduction/ increase?
divide difference in risk by control rate
e.g
e.g 100 patient take control and test drug. of control 50 develop disease, of tes 30 develop disease
relative risk = 0.5-0.3 = 0.2
relative risk reduction = 0.2/0.5 = 40%
what is the Fab and Fc region of Antibodies?
Fab - antigen binding fragment
Fc - constant region
what is the most common type of antibody found in the body?
IgG
which is the predominant Ab in breast milk?
IgA
which is the first Ab to be secreted in infection?
IgM
which Ab mediated type 1 hydpersensitivity?
IgE
which Ab is least abudant in serum?
IgE
which Ab protects against worms/ helminths?
IgE
where is ADH produced?
supraoptic nucleus of hypothalamus
what is the function of Anakinra
IL1 receptor antagonist
used in rheumatoid arthritis
which cells produce the following cytokines... IL1 IL2 IL3 IL4 IL5 IL6 IL8 IL10
IL1 - macrophages (fever, inflammation) IL2 - Th1 cells IL3, IL4, IL5 - Th2 cells IL6 - macrophages and TH2 IL8 - macrophages (neutrophil chemotaxis) IL10 - Th2
which cells produce the following cytokines…
TNFa
IFNg
TNFa - macrophages (induces fever, neutrophil chemotaxis)
IFNg - TH1 (activates macrophages)
which type of cancer should the following suggest…
Persistent unexplained hoarseness or pain in the throat, particularly in smokers with significant unexplained weight loss
oropharyngeal
risk factors - HPV
which cancers is EBV linked to?
Burkitt’s lymphoma
Hodgkin’s lymphoma
Post transplant lymphoma
Nasopharyngeal carcinoma
which cancers is HPV 16/18 linked to?
Cervical cancer Anal cancer Penile cancer Vulval cancer Oropharyngeal cancer
which cancer is the following linked to
Herpes virus 8
HTLV1
Herpes - Kaposi sarcoma
HTLV1 - adult T cell lymphoma
what type of disease is Leber’s optic atrophy
mitochondrial - maternal inheritance
what type of inheritance is seen with mitochondrial diseases?
affected man - none of children inherit
affected woman - all of children inherit.
in mitochondrial disease, what does muscle biopsy often show?
muscle biopsy classically shows ‘red, ragged fibres’ due to increased number of mitochondria
Giv examples of mitochondrial diseases…
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.
sensorineural hearing loss
describe steps of cardiac action potential…
Na in - depolatisation
K out - a little repolarisation
K out and Ca in - levels out the repolarisatin
K out only - repolarises
what is meant by parametric and non-parametric tests?
parametric - something that fits a normal distributed.
non-parametric - not normally distributed.
give examples of a parametric test
Student’s t-test - paired or unpaired*
Pearson’s product-moment coefficient - correlation
give examples of a non-parametric test and give a breif description.
Mann-Whitney U test
compares ordinal, interval, or ratio scales of unpaired data
Wilcoxon signed-rank test
compares two sets of observations on a single sample, e.g. a ‘before’ and ‘after’ test on the same population following an intervention
chi-squared test
used to compare proportions or percentages e.g. compares the percentage of patients who improved following two different interventions
Spearman, Kendall rank - correlation
what are the characteristics of congnital CMV infection?
growth retardation purpuric skin lesions - blueberry muffin skin Sensorineural deafness Encephalitis/seizures Pneumonitis Hepatosplenomegaly Anaemia Jaundice Cerebral palsy
what are the characteristics of congnital toxoplasmosis infection?
Cerebral calcification Chorioretinitis Hydrocephalus Hepatosplenomegaly Cerebral palsy anaemia
Congenital toxoplasmosis is the classic triad of cerebral calcification, chorioretinitis and hydrocephalus.
Can present later in childhood.
what are the characteristics of coggenital rubella infection?
Sensorineural deafness, cerebral palsy
Congenital cataracts, Glaucoma, ‘Salt and pepper’ chorioretinitis, Microphthalmia
Congenital heart disease (e.g. patent ductus arteriosus)
Growth retardation
Hepatosplenomegaly
Purpuric skin lesions - blueberry muffin rash
typically presents at birth
what is the function of the following cranial nerves…
a) I
b) II
c) III
d) IV
a) olfactory
b) optic
c) occulomotor - eye movement, pupil contriction, accomodation, eyelid opening
d) trochlea - eye movement
what is the function of the following cranial nerves…
a) V
b) VI
c) VII
d) VIII
a) trigeminal - facial sensation, mastication
b) abducens - eye movement
c) facial - face movements, tasteant 2/3, lacrimation, salivation
d) vesticulocochlea- hearing and balance
what is the function of the following cranial nerves…
a) IX
b) X
c) XI
d) XII
a) glossopharyngeal - swallow, post 1/3 taste, carotid sinus input
b) vagus - phonation, swallow
c) accessory - head and shoulder movement
d) hypoglosal - tongue movement
describe cranial nerve palsies III, IV and VI
III - Palsy results in ptosis, ‘down and out’ eye, dilated, fixed pupil
IV - Palsy results in defective downward gaze → vertical diplopia
VI- Palsy results in defective abduction → horizontal diplopia
describe cranial nerve palsy X and XII
X - uvula deviates away from site of lesion
XII - tongue deviates towards site of lesion.
which nerves are involved in the following reflexes.... corneal jaw jerk gag pupilary light lacrimation
corneal - opthalmic and facial jaw jerk - trigeminal gag - glossopharyngeal, vagus pupillary light - optic, occulomotor lacrimation - opthalmic, facial.
first = sensory, second = motor
what is sensitivity?
Proportion of patients with the condition who have a positive test result
what is specificity?
Proportion of patients without the condition who have a negative test result
what is positive predictive value?
The chance that the patient has the condition if the diagnostic test is positive
what is the negative predictive value?
The chance that the patient does not have the condition if the diagnostic test is negative
which cells produce the different interferons?
IFNa - leukocytes - antiviral actions
IFNb - fibroblasts - antiviral action.
IFNg - NK and T helper cells.- granulomatous disease
what is the chloride shift in RBC?
Chloride shift
CO2 diffuses into RBCs
CO2 + H20 —- carbonic anhydrase -→ HCO3- + H+
H+ combines with Hb
HCO3- diffuses out of cell,- Cl- replaces it
what is haldane effect?
increase pO2 means CO2 binds less well to Hb
when are levels of endothelin raised?
MI heart failure ARF asthma primary pulmonary hypertension
what inhibits the release of endothelin?
NO
prostacyclin
what promotes the release of endothelin?
ADH
angiotensin,
sheer stress
hypoxia
what immunological changes are seen in progressive HIV?
reduction in CD4 count increase B2-microglobulin decreased IL-2 production polyclonal B-cell activation decrease NK cell function reduced delayed hypersensitivity responses
what are the roots of the radial nerve?
C5 to T1
what is the function of the radial nerve?
motor:
Triceps, Anconeus, Brachioradialis, Extensor carpi radialis, Supinator, Abductor pollicis longus and all other extensor muscles
sensory: dorsal aspect of hand except little and rign finger.
what happens if radial nerve is damaged?
at axila…
wrist drop
sensory loss to small area between the dorsal aspect of the 1st and 2nd metacarpals
and paralysis of triceps
how is standard error of mean calculateD?
SD / square root (n)
standard deviation / square root of number of people
how are 95% confidence intervals calculated?
A 95% confidence interval:
lower limit = mean - (1.96 * SEM)
upper limit = mean + (1.96 * SEM)
how is the power of a study calculated?
Power = 1 - the probability of a type II error
Power means correctly identifying the result regardless of whether the hypothesis is accepted or rejected. A study with high power can accurately identify an effect or difference when one exists or vice versa.
power can be increased by increasing the sample size
what is a type 1 and type 2 error?
type I: the null hypothesis is rejected when it is true - i.e. Showing a difference between two groups when it doesn’t exist, a false positive. his is determined against a preset significance level (termed alpha).
type II: the null hypothesis is accepted when it is false - i.e. Failing to spot a difference when one really exists, a false negative. The probability of making a type II error is termed beta. It is determined by both sample size and alpha
what are the majority of brain tumours?
gliomas and metastatic disese
what are the levels of evidence?
Ia - evidence from meta-analysis of randomised controlled trials
Ib - evidence from at least one randomised controlled trial
IIa - evidence from at least one well designed controlled trial which is not randomised
IIb - evidence from at least one well designed experimental trial
III - evidence from case, correlation and comparative studies
IV - evidence from a panel of experts
what are the grading of recommendations?
Grade A - based on evidence from at least one randomised controlled trial (i.e. Ia or Ib)
Grade B - based on evidence from non-randomised controlled trials (i.e. IIa, IIb or III)
Grade C - based on evidence from a panel of experts (i.e. IV)
what form of inheritence is homocysteinuria?
auto recessive
what are the features of homocysteinuria?
often patients have fine, fair hair
Marfanoid body habitus: arachnodactyly etc
osteoporosis
kyphosis
neurological: may have learning difficulties, seizures
downwards (inferonasal) dislocation of lens
severe myopia
increased risk of arterial and venous thromboembolism
also malar flush, livedo reticularis
how is homocysteinuria investigated?
increased homocysteine levels in serum and urine
cyanide-nitroprusside test: also positive in cystinuria
how is homocysteinuria treated?
pyroxidine (vit B6)
what is fabry disease?
X-linked recessive
deficiency of alpha-galactosidase A
A. Alpha-galactosidase A normally breaks down a fatty substance called globotriaosylceramide. As a result, this fatty substance builds up in the cells of your body particularly cells lining blood vessels in the skin and cells in the kidneys, heart, and nervous system.
what are the features of fabry disease?
Features
burning pain/paraesthesia in childhood - in hands and feet
angiokeratomas - clusters of small, dark red spots on the skin
lens opacities
proteinuria
early cardiovascular disease
decreased ability to sweat (hypohidrosis);
tinnitus/ hear loss
what is the wilson and junger screening criteria?
- The condition should be an important public health problem
- There should be an acceptable treatment for patients with recognised disease
- diagnosis and treatment should be available
- There should be a recognised latent or early symptomatic stage
- The natural history of the condition should be adequately understood
- There should be a suitable test or examination
- The test or examination should be acceptable to the population
- There should be agreed policy on whom to treat
- The cost of case-finding should be economically balanced
- Case-finding should be a continuous process and not a ‘once and for all’ project
what rule can be used to work out if a disease is auto dominant/ recessive?
Autosomal recessive conditions are ‘metabolic’ - exceptions: inherited ataxias
Autosomal dominant conditions are ‘structural’ - exceptions: hyperlipidaemia type II, hypokalaemic periodic paralysis
What is the trend of risk of down sydnrome and maternal age?
20 1 in 1,500 30 1 in 800 35 1 in 270 40 1 in 100 45 1 in 50 or greater
One way of remembering this is by starting at 1/1,000 at 30 years and then dividing the denominator by 3 (i.e. 3 times more common) for every extra 5 years of age
how do majority of down syndrome cases arise?
non dysjunction
also by robertsonian translocation
what are the following HLA associated with? HLA A3 HLA B51 HLAB27 HLADQ2/8
HLA-A3
haemochromatosis
HLA-B51
Behcet’s disease
HLA-B27
ankylosing spondylitis
reactive arthritis
acute anterior uveitis
HLA-DQ2/DQ8
coeliac disease
what are the following HLA associated with?
HLADR2
HLA DR3
HLA DR4
HLA-DR2
narcolepsy
Goodpasture’s
HLA-DR3 dermatitis herpetiformis Sjogren's syndrome primary biliary cirrhosis (T1D - but stronger association with DR4)
HLA-DR4
type 1 diabetes mellitus*
rheumatoid arthritis
which enzyme is deficient in homocysteinuria?
cystathionine beta synthase
what classification is used for hypersensitivity?
Gells and coombs
what is type 1 hypersensitivity?
IgE bound mast cell
anaphylaxis
atopy
what is type 2 hypersensitivity? with examples
IgG or IgM binds to antigen on cell surface
- Autoimmune haemolytic anaemia
- ITP
- Goodpasture’s syndrome
- Pernicious anaemia
- Acute haemolytic transfusion reactions
- Rheumatic fever
- Pemphigus vulgaris / bullous pemphigoid
what is type 3 hypersensitivity ? with examples?
Free antigen and antibody (IgG, IgA) combine
- Serum sickness
- Systemic lupus erythematosus
- Post-streptococcal glomerulonephritis
- Extrinsic allergic alveolitis (especially acute phase)
what is type 4 hypersensitivity?
T-cell mediated
- Tuberculosis / tuberculin skin reaction
- Graft versus host disease
- Allergic contact dermatitis
- Scabies
- Extrinsic allergic alveolitis (especially chronic phase)
- Multiple sclerosis
- Guillain-Barre syndrome
what is type 5 hypersensitivity?
Antibodies that recognise and bind to the cell surface receptors.
This either stimulating them or blocking ligand binding
graves, myasthenia gravis etc
where does the ulnar nerve arise?
medial cord - c8, T1
what is the function of the ulnar nerve?
medial 2 lumbricals,
hypothenar muscles
flexor carpi ulnaris
interossei
sensory to medial two fingers - palmar and dorsal
what happens if ulnar nerve is damaged at
a) wrist
b) elbow
at wrist
‘claw hand’ - hyperextension of the metacarpophalangeal joints and flexion at the distal and proximal interphalangeal joints of the 4th and 5th digits
wasting and paralysis of intrinsic hand muscles (except lateral two lumbricals)
wasting and paralysis of hypothenar muscles
sensory loss to the medial 1 1/2 fingers (palmar and dorsal aspects)
Damage at elbow
as above (however, ulnar paradox - clawing is more severe in distal lesions)
radial deviation of wrist
what does troponin I , T and C bind?
troponin C: binds to calcium ions
troponin T: binds to tropomyosin,
troponin I: binds to actin to hold the troponin-tropomyosin complex in place
what is the variance?
standard deviation squared
what inhibits prolactin releasE?
dopamine e.g. cabergoline
what can increase prolactin release?
pregnancy, oestrogen, breast feeding , stress
metaclopromide
give examples of tyrosine kinase receptors…
receptor tyrosine kinase: insulin, insulin-like growth factor (IGF), epidermal growth factor (EGF)
give examples of guanyl cyclase receptors?
contain intrinsic enzyme activity
e.g. atrial natriuretic factor, brain natriuretic peptide
what are the different types of GPCRs?
Gs: Stimulates adenylate cyclase → increases cAMP → activates protein kinase A
Gi: Inhibits adenylate cyclase → decreases cAMP → inhibits protein kinase A
Gq:
Activates phospholipase C → splits PIP2 to IP3 & DAG → activates protein kinase C
what is primary hyperparathyroidism?
PTH (Elevated)
Ca2+ (Elevated)
Phosphate (Low)
Urine calcium : creatinine clearance ratio > 0.01
May be asymptomatic if mild
Most cases due to solitary adenoma (80%), multifocal disease occurs in 10-15% and parathyroid carcinoma in 1% or less
what is secondary hyperparathyroidism?
PTH (Elevated)
Ca2+ (Low or normal)
Phosphate (Elevated)
Vitamin D levels (Low)
May have few symptoms
Eventually may develop bone disease, osteitis fibrosa cystica and soft tissue calcifications
Parathyroid gland hyperplasia occurs as a result of low calcium, almost always in a setting of chronic renal failure
what is tertiary hyperparathyroidism?
Ca2+ (Normal or high)
PTH (Elevated)
Phosphate levels (Decreased or Normal)
Vitamin D (Normal or decreased) Alkaline phosphatase (Elevated) Metastatic calcification Bone pain and / or fracture Nephrolithiasis Pancreatitis Occurs as a result of ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder, hyperplasia of all 4 glands is usually the cause
what is achondroplasia?
Achondroplasia is an autosomal dominant disorder associated with short stature.
It is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene.
this results in abnormal cartilage
what are the features of achondroplasia?
short limbs (rhizomelia) with shortened fingers (brachydactyly)
large head with frontal bossing and narrow foramen magnum
midface hypoplasia with a flattened nasal bridge
‘trident’ hands
lumbar lordosis
how do majority of cases of achondroplasia occur?
random sporadic mutation
once present inherited as auto dominant
what is the main risk factor for achondroplasia?
paternal age at conception
what are the causes of acute tubular necrosis?
ischaemia - shock, sepsis
nephrotoxins - aminoglycosides, myoglobin secondary to rhabdomyolysis, radiocontrast agents and lead
what is seen in urine in acute tubular necrosis?
muddy brown casts
what are the phases of acute tubular necrosis?
oliguric phase
polyuric phase
recovery phase
what is alkaptonuria?
Alkaptonuria (ochronosis) is a rare autosomal recessive disorder of phenylalanine and tyrosine metabolism caused by a lack of the enzyme homogentisic dioxygenase (HGD) which results in a build-up of toxic homogentisic acid.
The kidneys filter the homogentisic acid (hence black urine) but eventually it accumulates in cartilage and other tissues.
what are the features of alkaptonuria?
pigmented sclera
urine turns black if left exposed to the air
intervertebral disc calcification may result in back pain
renal stones
how is alkaptonuria managed?
high-dose vitamin C
dietary restriction of phenylalanine and tyrosine
what are the functions of vit C?
antioxidant
collagen synthesis: acts as a cofactor for enzymes that are required for the hydroxylation proline and lysine in the synthesis of collagen
facilitates iron absorption
cofactor for norepinephrine synthesis
how does vit C deficiency present?
gingivitis, loose teeth poor wound healing bleeding from gums, haematuria, epistaxis general malaise Follicular hyperkeratosis and perifollicular haemorrhage Ecchymosis, easy bruising Sjogren's syndrome Arthralgia Oedema
describe the location of the following dermatomes C2 C3 C4 C5
C2 Posterior half of the skull (cap)
C3 High turtleneck shirt
C4 Low-collar shirt
C5 Ventral axial line of upper limb
describe the location of the following dermatomes C6 C7 C8 T1 T2
C6 Thumb + index finger C7 Middle finger + palm of hand C8/ T1 Ring + little finger T1 - inner lower arm T2 - inner upper arm
describe the location of the following dermatomes T4/5 T10 L1 L4 L5
T4/5 nipple T10 - belly button L1 Inguinal ligament L4 Knee caps L5 Big toe, dorsum of foot (except lateral aspect)
describe the location of the following dermatomes
S1
S2/3
S1 lateral foot
S2/3 - genitals
what is meant by incidence and prevalence?
The incidence is the number of new cases per population in a given time period.
The prevalence is the total number of cases per population at a particular point in time
prevalence = incidence * duration of condition
in chronic diseases the prevalence is much greater than the incidence
what are the 5 principles of mental capacity act?
assumed to have capacity unless it is established that he lacks capacity
not to be treated as unable to make a decision unless all practicable steps to help him
not to be treated as unable to make a decision merely because he makes an unwise decision
An act done, or decision made,for a person who lacks capacity must in his best interests
Before the act is done regard to whether the purpose for which it is needed can be as effectively achieved in a way that is less restrictive of the person’s rights and freedom of action
what is the difference between prostacyclins and thromboxane?
thromboxane - platelet aggregation and vasoconstriction
prostacyclins - vasodilation and reduced platelet aggregation
what is atrial natureitic peptide?
secreted mainly from myocytes of right atrium and ventricle in response to increased blood volume
secreted by both the right and left atria (right»_space; left)
natriuretic, i.e. promotes excretion of sodium
lowers BP
antagonises actions of angiotensin II, aldosterone
what is meant by non-penetrance?
lack of clinical signs and symptoms (normal phenotype) despite abnormal gene.
All of the following conditions follow which type of inheritance?
Acute intermittent porphyria Ehlers-Danlos syndrome Hereditary spherocytosis Hyperlipidaemia type II Hypokalaemic periodic paralysis Marfan's syndromes Myotonic dystrophy Neurofibromatosis Noonan syndrome Osteogenesis imperfecta Peutz-Jeghers syndrome tuberous sclerosis
auto dominant
what is selection bias?
Error in assigning individuals to groups leading to differences which may influence the outcome.
e.g. sampling bias , non-responder bias, healthy worker effect
what is recall bias?
Difference in the accuracy of the recollections retrieved by study participants, possibly due to whether they have disorder or not. E.g. a patient with lung cancer may search their memories more thoroughly for a history of asbestos exposure than someone in the control group. A particular problem in case-control studies.
what is publication bias?
Failure to publish results from valid studies, often as they showed a negative or uninteresting result. Important in meta-analyses where studies showing negative results may be excluded.
what is expectation bias?
Only a problem in non-blinded trials. Observers may subconsciously measure or report data in a way that favours the expected study outcome.
what is the hawthorne effect?
Describes a group changing it’s behaviour due to the knowledge that it is being studied
what is lead time bias?
Occurs when two tests for a disease are compared, the new test diagnoses the disease earlier, but there is no effect on the outcome of the disease
what is the origin of the brachial plexus?
anterior rami of C5-T1
in terms of location, where doadult tumours lie in comparison to childhood tumours
the majority of adult tumours are supratentorial, where as the majority of childhood tumours are infratentorial.
which tumours metastasise to the brain?
lung (most common) breast bowel skin (namely melanoma) kidney
what is the most common primary tumour of the brain? what is the prognosis?
Glioblastoma
poor prognosis - around 1 year
how does glioblastoma present on imaging and histologically
On imaging they are solid tumours with central necrosis and a rim that enhances with contrast. Disruption of the blood-brain barrier and therefore are associated with vasogenic oedema.
Histology: Pleomorphic tumour cells border necrotic areas
what is the second most common brain tumour in adults (after glioblastoma)? what is their prognosis like?
meningioma
Meningiomas are typically benign, extrinsic tumours of the central nervous system. They arise from the dura mater of the meninges and cause symptoms by compression rather than invasion.
where do majority of meningiomas form?
they typically are located at the falx cerebri, superior sagittal sinus, convexity or skull base.
how do meningiomas present histologically?
Spindle cells in concentric whorls and calcified psammoma bodies
how does a vestibular schwannoma present?
Hearing loss, facial nerve palsy (due to compression of the nearby facial nerve) and tinnitus.
what is a vestibular schwannoma ?
a.k.a acoustic neuroma
benign tumour arising from 8th cranial nerve
often seen in cerebellopontine angle
which genetic condition is associated with B/L vestibular schwannoma ?
Neurofibromatosis type 2
what is the most common type of brain tumour in children and what is its histology?
Pilocytic astrocytoma Rosenthal fibres (corkscrew eosinophilic bundle)
what is a Medulloblastoma? what is the treatment and histology?
aggressive paediatric brain tumour that arises within the infratentorial compartment. It spreads through the CSF system. Treatment is surgical resection and chemotherapy.
: Small, blue cells. Rosette pattern of cells with many mitotic figures
what is an oligodendroma? including histology
enign, slow-growing tumour common in the frontal lobes
• Histology: Calcifications with ‘fried-egg’ appearance
what genetic condition is Haemangioblastoma associated with ?
Haemangioblastoma is a vascular tumour
associated with von Hippel-Lindau syndrome
where is a Craniopharyngioma derived from?
Rathke pouch
most common paediatric supratentorial tumour
which drugs should be avoided in breast feeding?
antibiotics: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides
psychiatric drugs: lithium, benzodiazepines
aspirin carbimazole methotrexate sulfonylureas cytotoxic drugs amiodarone
which type of inheritance are all of the following: Androgen insensitivity syndrome Becker muscular dystrophy Duchenne muscular dystrophy Fabry's disease G6PD deficiency Haemophilia A,B Hunter's disease Lesch-Nyhan syndrome Nephrogenic diabetes insipidus Ocular albinism Retinitis pigmentosa Wiskott-Aldrich syndrome
X linked recessive
which conditions are inherited in an 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 is williams syndrome?
William’s syndrome is an inherited neurodevelopmental disorder caused by a microdeletion on chromosome 7
what are the features of williams syndrome?
elfin-like facies characteristic like affect - very friendly and social learning difficulties short stature transient neonatal hypercalcaemia supravalvular aortic stenosis
How is Williams syndrome diagnosed?
FISH studies
how is vitamin K absorbed? how may it become deficient?
fat soluble and thus with fat
absorption may be affected in conditions affecting fat absorption
Also can become deficient after prolonged use of broad-spectrum antibiotics by eliminating the gut flora
what is vitamin D resistant crickets?
X linked dominant
issue with phosphate reabsorption in kidneys
leads to failure to thrive,
what are the lab and imaging results in Vit D resistant rickets?
normal serum calcium, low phosphate, elevated alkaline phosphotase
x-ray changes: cupped metaphyses with widening of the epiphyses
Diagnosis is made by demonstrating increased urinary phosphate
how is vit D resistant rickets managed?
Management
high-dose vitamin D supplements
oral phosphate supplements
what are the functions of vit D?
increases plasma calcium and plasma phosphate
increases renal tubular reabsorption and gut absorption of calcium
increases osteoclastic activity
increases renal phosphate reabsorption
which drug causes vit B6 (pyroxidine) deficiency?
isoniazid
what are the consequences of vit B6 deficiency?
peripheral neuropathy
sideroblastic anemia
which diseases disrupt vit b3 levels?
Hartnup’s disease: hereditary disorder which reduces absorption of tryptophan
carcinoid syndrome: increased tryptophan metabolism to serotonin
what are the consequences of vit B3 deficiency?
Consequences of niacin deficiency:
pellagra: dermatitis, diarrhoea, dementia
what are the following vitamins also known as? vit B6 Vit B3 vit B2 B1
B6 - pyroxidine
B3 - niacin
b2 - riboflavin
b1 - thiamine
what are the consequencses of B2 deficiency?
angular cheilitis
what are the consequences of thiamine deficiency?
Wernicke’s encephalopathy: nystagmus, ophthalmoplegia and ataxia
Korsakoff’s syndrome: amnesia, confabulation
dry beriberi: peripheral neuropathy
wet beriberi: dilated cardiomyopathy
when are the following casts seen?
red blood cell casts
white blood cell cast
muddy brown casts
Red blood cell casts Glomerulonephritis
Renal ischaemia and infarction
White blood cell casts Acute pyelonephritis
Interstitial nephritis
Granular (‘muddy-brown’) casts Acute tubular necrosis
when are the following cast seen?
hyaline
epithlial
waxy
fatty
Hyaline casts Common and non-specific
May be seen following exercise or dehydration
Epithelial casts Acute tubular necrosis
Waxy casts Advanced chronic kidney disease
Fatty casts Nephrotic syndrome
what is the motor and sensory function of musculoskeletal nerve?
Musculocutaneous nerve (C5-C7) Elbow flexion (supplies biceps brachii) and supination
Sensory: Lateral part of the forearm
what is the motor and sensory function of axillary nerve?
Axillary nerve (C5,C6) Shoulder abduction (deltoid muscle) Inferior region of the deltoid muscle
what is the motor and sensory function of radial nerve?
Radial nerve (C5-C8) Extension (forearm, wrist, fingers, thumb) Small area between the dorsal aspect of the 1st and 2nd metacarpals
what is the motor and sensory function of median nerve?
LOAF* muscles: Lateral two lumbricals Opponens pollis Abductor pollis brevis Flexor pollis brevis
Palmar aspect of lateral 3½ fingers
what is the motor and sensory function of ulnar nerve?
Ulnar nerve (C8, T1) Intrinsic hand muscles except LOAF* Wrist flexion
Medial 1½ fingers
what does the long thoracic nerve supply?
what does damage result in
serratus anterior
damage results in winged scapula
what is erbs palsy?
Erb-Duchenne palsy (‘waiter’s tip’)
due to damage of the upper trunk of the brachial plexus (C5,C6)
may be secondary to shoulder dystocia during birth
the arm hangs by the side and is internally rotated, elbow extended
what is klumpkes palsy?
Klumpke injury
due to damage of the lower trunk of the brachial plexus (C8, T1)
as above, may be secondary to shoulder dystocia during birth. Also may be caused by a sudden upward jerk of the hand
associated with Horner’s syndrome
what is turners?
45,XO
what are the features of turners
short stature
shield chest, widely spaced nipples
webbed neck
bicuspid aortic valve & coarctation of the aorta
primary amenorrhoea
cystic hygroma
high-arched palate
short fourth metacarpal
multiple pigmented naevi
lymphoedema in neonates (especially feet)
gonadotrophin levels will be elevated
hypothyroidism is much more common in Turner’s
horseshoe kidney: the most common renal abnormality in Turner’s syndrome
increased autoimmunity - e.g crohns
The following tumour suppressor genes are associated with which cancers?
p53 APC NF1 WT1 MTS1 (multiple tumour supressor 1)
p53 Common to many cancers, Li-Fraumeni syndrome
APC Colorectal cancer
NF1 Neurofibromatosis
Rb Retinoblastoma
WT1 Wilm’s tumour
Multiple tumor suppressor 1 (MTS-1, p16) Melanoma
when is surfactant first detectable?
28 weeks
how can trinucleotide repeat disorders affect successive generations? what is this concept known as?
more severe/ earlier onset as generations go on
This is known as anticipation
what are the following types of? •Fragile X (CGG) •Huntington's (CAG) •myotonic dystrophy (CTG) •Friedreich's ataxia* (GAA) •spinocerebellar ataxia •spinobulbar muscular atrophy •dentatorubral pallidoluysian atrophy
trinucleotide repeat disorders
which of the trinucleotide repeat disorders does not show anticipation?
Friedreich’s ataxia
what is the function of PTH?
Increase calcium levels and decrease phosphate levels
Increases bone resorption
Immediate action on osteoblasts to increase ca2+ in extracellular fluid
Osteoblasts produce a protein signaling molecule that activate osteoclasts which cause bone resorption
Increases renal tubular reabsorption of calcium
Increases synthesis of 1,25(OH)2D (active form of vitamin D) in the kidney which increases bowel absorption of Ca2+
Decreases renal phosphate reabsorption
what is the role of vitamin D?
Increases plasma calcium and plasma phosphate
Increases renal tubular reabsorption and gut absorption of calcium
Increases osteoclastic activity
Increases renal phosphate reabsorption in the proximal tubule
what is the role of calcitonin?
Secreted by C cells of thyroid
Inhibits osteoclast activity (osteoclasts break down bone)
Inhibits renal tubular absorption of calcium
what hormones play a role in Ca metabolism?
PTH, vit D, calcitonin, thyroid hormones, growth hormones
what is the formula for systemic vascular resistance?
mean arterial pressure/cardiac output
where are lysosomal proteins made and modified?
made in RER
modified by golgi - by ading mannose 6 phosphate
what is the equation for cerebral perfusion pressure?
CPP= Mean arterial pressure - Intra cranial pressure
what is nominal data?
qualitative data which groups variables into categories.
e..g type of bike, birth place
cant be ordered
what is ordinal data?
Observed values can be put into set categories which themselves can be ordered (for example NYHA classification of heart failure symptoms)
what is discrete data?
Observed values are confined to a certain values, usually a finite number of whole numbers (for example the number of asthma exacerbations in a year)
what is binomial data?
2 values e.g. gender
what are the clinical features of down syndrome?
face: upslanting palpebral fissures, epicanthic folds, Brushfield spots in iris, protruding tongue, small low-set ears, round/flat face
flat occiput
single palmar crease, pronounced ‘sandal gap’ between big and first toe
hypotonia
congenital heart defects (40-50%, see below)
duodenal atresia
Hirschsprung’s disease
subfertility: males are almost always infertile due to impaired spermatogenesis. Females are usually subfertile, learning difficulties short stature repeated respiratory infections (+hearing impairment from glue ear) acute lymphoblastic leukaemia hypothyroidism Alzheimer's disease atlantoaxial instability
what cardiac issues can be seen in downs?
endocardial cushion defect (most common, 40%, also known as atrioventricular septal canal defects)
ventricular septal defect (c. 30%)
secundum atrial septal defect (c. 10%)
tetralogy of Fallot (c. 5%)
isolated patent ductus arteriosus (c. 5%)
how are the effects of confounding factors minimised?
randomisation
stratification
what is the difference between linear regression and correlation?
correlation betwen -1 and +1
linear regression - exact relationship y=ax+ b
what are the key features of patau syndrome (trisomy 13)?
Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions
what are the key features of Edwards syndrome (trisomy 18)?
Micrognathia
Low-set ears
Rocker bottom feet
Overlapping of fingers
what are the clinical features of fragile X?
Learning difficulties Macrocephaly Long face Large ears Macro-orchidism high arched palate hypotonia autism is more common mitral valve prolapse
what are the clinical features of noonans?
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis
what are the clinical features of pierre robins syndrome?
Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate
what are the clinical features of prader wili syndrome?
Hypotonia
Hypogonadism
Obesity
what are the clinical features of williams syndrome?
Short stature Learning difficulties Friendly, extrovert personality Transient neonatal hypercalcaemia Supravalvular aortic stenosis
what are the clinical features of Cri du chat syndrome ? (chrom 5p deletion)
Characteristic cry (hence the name) due to larynx and neurological problems
Feeding difficulties and poor weight gain
Learning difficulties
Microcephaly and micrognathism
Hypertelorism
Pierre robin and Treacher colins present similarly, how can they be distinguished?
Treacher-Collins syndrome is autosomal dominant so there is usually a family history of similar problems
How many phases are in a clinical trial? Describe each.
I Determines pharmacokinetics and pharmacodynamics and side-effects prior to larger studies Conducted on healthy volunteers
II Assess efficacy + dosage Involves small number of patients affected by particular disease
III Assess effectiveness Typically involves 100-1000’s of people, often as part of a randomised controlled trial, comparing new treatment with established treatments
IV Postmarketing surveillance Monitors for long-term effectiveness and side-effects
what conditions are associated with collagen I, III, IV, V
I - osteogenia imperfecta
III - vascular ehlos danlos
IV - goodpastures, alports
V - classic ehlers danlos
which cells synthesise collagen? what cofactor is involved?
fibroblast
vitamin C
what histological changes are seen in diabetic nephropathy?
histological changes include: basement membrane thickening, capillary obliteration, mesangial widening. Nodulular hyaline areas develop in the glomuli - Kimmelstiel-Wilson nodules
what are the risk factors for developing diabetic nephropathy?
male genetics duration of diabetes HTN glycaemic control smoking hyperlipidaemia dietary protein
what is diGeorge syndrome?
deletion of chrom 22q11.2 - micro deletion
immunodeficiency caused by T cell dysfunction
what are the features of DiGeorge?
C - Cardiac abnormalities
A - Abnormal facies
T - Thymic aplasia - viral and fungal infection
C - Cleft palate
H - Hypocalcaemia/ hypoparathyroidism (aplasia)
22 - Caused by chromosome 22 deletion
what are the layers of the epidermis?
Stratum corneum: Flat, dead, scale-like cells filled with keratin Continually shed
Stratum lucidum Clear layer - present in thick skin only
Stratum granulosum Cells form links with neighbours
Stratum spinosum Squamous cells begin keratin synthesis. Thickest layer of epidermis
Stratum germinativum The basement membrane - single layer of columnar epithelial cells. Gives rise to keratinocytes. Contains melanocytes
what type of epithelium is the epidermis?
stratified squamous
where does erythropoeisis occur?
red bone marrow found primarily in flat bones (including the vertebrae, ribs, and sternum) and the proximal ends of long bones in adults. In the foetus, erythrocytes are produced mainly in the liver.
what are stages of RBC development?
Haematocytoblast Multipotent stem cell for all types of blood cells
Proerythroblast Cell has become committed to its developmental pathway
Basophilic erythroblast Ribosomes start to accumulate and the nucleus begins to shrink
Polychromatophilic erythroblast Nucleus and total cell volume continue to shrink
Normoblast Cell nucleus is ejected before developing further
Reticulocyte Cells enter the circulation
Erythrocyte Fully matured cell
process takes around 1 week
which drugs interfere with folate metabolism/.absorption?
Drugs which interfere with metabolism
trimethoprim
methotrexate
pyrimethamine
Drugs which can reduce absorption
phenytoin
how does fragile X present in females compared to males?
Features in females (who have one fragile chromosome and one normal X chromosome) range from normal to mild.
males have all features
how can fragile X be diagnosed?
can be made antenatally by chorionic villus sampling or amniocentesis
analysis of the number of CGG repeats
which cardiovascular diseases are a contrindication for flying?
unstable angina, uncontrolled hypertension, uncontrolled cardiac arrhythmia, decompensated heart failure, severe symptomatic valvular disease: should not fly
what are the rules around flying after MI?
uncomplicated myocardial infarction: may fly after 7-10 days
complicated myocardial infarction: after 4-6 weeks
what are the rules for flying after CABG/ PCI?
coronary artery bypass graft: after 10-14 days
percutaneous coronary intervention: after 3 days
what are the rules about flying after stroke?
stroke: patients are advised to wait 10 days following an event, although if stable may be carried within 3 days of the event
what are the rules for flying after pneumothorax?
the CAA suggest patients may travel 2 weeks after successful drainage if there is no residual air. The British Thoracic Society used to recommend not travelling by air for a period of 6 weeks but this has now been changed to 1 week post check x-ray
what are the rules for flying when pregnant?
most airlines do not allow travel after 36 weeks for a single pregnancy and after 32 weeks for a multiple pregnancy
most airlines require a certificate after 28 weeks confirming that the pregnancy is progressing normally
what are rules around flying after surgery?
travel should be avoided for 10 days following abdominal surgery
laparoscopic surgery: after 24 hours
colonoscopy: after 24 hours
following the application of a plaster cast, the majority of airlines restrict flying for 24 hours on flights of less than 2 hours or 48 hours for longer flights
what is a funnel plot?
A funnel plot is primarily 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.
a symmetrical, inverted funnel shape indicates that publication bias is unlikely
what increases and decreases GH secretion?
Increases secretion growth hormone releasing hormone (GHRH) fasting exercise sleep (particularly delta sleep)
Decreases secretion
glucose
somatostatin (itself increased by somatomedins,
what immunological changes are seen in HIV?
reduction in CD4 count increase B2-microglobulin decreased IL-2 production polyclonal B-cell activation decrease NK cell function reduced delayed hypersensitivity responses
what is the function of IL1?
secreted mainly by macrophages and monocytes and acts as a costimulator of T cell and B cell proliferation.
mediator of shock in sepsis
produces fever (along with IL6 and TNF)
what are IL1 inhibitors?
anakinra - IL-1 receptor antagonist
used in the management of rheumatoid arthritis
canakinumab- monoclonal antibody targeted at IL-1 beta
used systemic juvenile idiopathic arthritis and adult-onset Still’s disease
which MHC do T helper and cytotoxic T cells recognise?
MHC class I - cytotoxic T class II - T helper
which immune cells are involved in organ rejection?
cytotoxic T - mediates acute and chronic organ rejection
B cells - mediate hyperacute organ rejection
What is Von gierke’s disease? (type 1 glycogen storage disease)
deficiency in glucose-6-phosphatase
Hepatic glycogen accumulation. Key features include hypoglycaemia, lactic acidosis, hepatomegaly
what is Pompe’s disease (type II glycogen storage disease)?
Lysosomal alpha-1,4-glucosidase defieciency
Cardiac, hepatic and muscle glycogen accumulation. Key features include cardiomegaly
what is Cori disease (type III glycogen storage disease)?
Alpha-1,6-glucosidase (debranching enzyme) deficiency
Hepatic, cardiac glycogen accumulation. Key features include muscle hypotonia
what is McArdles disease (type 4 glycogen storage disease)?
Glycogen phosphorylase (myophosphorylase) deficiency. Skeletal muscle glycogen accumulation. Key features include myalgia, myoglobinuria with exercise
what is Gauchers disease?
Beta-glucocerebrosidase deficiency
lysosomal storage disease
Most common lipid storage disorder resulting in accumulation of glucocerebrosidase in the brain, liver and spleen. Key features include hepatosplenomegaly, aseptic necrosis of the femur
What is Tay Sachs disease?
Deficiency in Hexosaminidase
Lysosomal storage disease
Accumulation of GM2 ganglioside within lysosomes. Key features include developmental delay, cherry red spot on the macula, liver and spleen normal size (cf. Niemann-Pick)
What is Niemann Pick disease?
deficiency in Sphingomyelinase
lysosomal storage disease
Key features include hepatosplenomegaly, cherry red spot on the macula
What is Fabry disease?
lysosomal storage disease
deficiency in Alpha-galactosidase-A
Accumulation of ceramide trihexoside. Key features include angiokeratomas, peripheral neuropathy of extemeties, renal failure
The following are both examples of what type of disease?
Krabbe’s disease
Metachromatic leukodystrophy
Lysosomal storage disease.
name two Mucopolysaccharidoses
give one similarity and one difference
Hunter syndrome
Hurlers syndrome
both have accumulation of glycosaminoglycans
corneal clouding in hurlers but NOT in hunters
where is iron absorbed?
upper small intestine especially the duodenum
Fe2+ is better absorbed than fe3+
what increases/decreases iron absorption?
increased - vit C
decreased - low acid, tannin (found in tea), PPI, tetracycline
how is iron transported and stored?
transported as fe3+ bound to transferrin
stored bound to ferritin in tissues
What is McCune Albright syndrome?
McCune-Albright syndrome is not inherited, it is due to a random, somatic mutation in the GNAS gene.
Features precocious puberty cafe-au-lait spots polyostotic fibrous dysplasia short stature
what is the motor and sensory function of the femoral nerve?
Knee extension, thigh flexion
Anterior and medial aspect of the thigh and lower leg
what is the motor and sensory function of the obturator nerve?
Thigh adduction
Medial thigh
what is the motor and sensory function of the tibial nerve?
Foot plantarflexion and inversion
Sole of foot
what is the motor and sensory function of common peroneal nerve?
Foot dorsiflexion and eversion
Extensor hallucis longus
Dorsum of the foot and the lower lateral part of the leg
what is the function of the superior and inferior gluteal nerves?
Hip abduction - superior
Hip extension and lateral rotation - inferior
what is the function of kinesin and dynein?
Kinesin - moves stuff along microtubules from centre to periphery
dynein - moves from periphery to centre
what is the difference between southern, northern and western blotting?
Southern = Detects DNA
Northern blotting= Detects RNA
Western blotting = Detects proteins
what tests are used for HIV testing?
Elisa - initial test
Western blotting for confirmation test
when is a temporal artery biopsy recomended?
Age of onset older than 50 years
New-onset headache or localized head pain
Temporal artery tenderness to palpation or reduced pulsation
ESR > 50 mm/h
what histology is seen in temporal arteritis?
Vessel wall granulomatous arteritis with mononuclear cell infiltrates and giant cell formation
what are contraindication to temporal artery biopsy?
glucocorticoids >30 days
which nerve is at risk of damage in temporal artery biopsy?
facial or auriculotemporal nerve
describe steps of muscle contraction…
- action potential at NMJ –> release of ACH
- ACh binds receptors –> Na ions in –> depolarisation through T tubules
- L type VG Ca channels (dihydropyridine receptors) –> Ca in
- Triggers ryanodine receptors on sarcoplasmic reticulum –> More Ca
- Ca binds to troponin C (found on actin-containing thin filaments) causing a conformational change, allowing tropomyosin to move, unblocking the binding sites
- myosin binds to the newly released binding site releasing ADP, pulling the Z bands towards each other
- ATP binds to myosin, releasing actin
- ATP hydrolysed and myosin bends back to original position.
what does the following contain..
I band, A band, H zone , M line, Z line
I-band Zone of thin filaments that is not superimposed by thick filaments …. actin only
A-band Contains the entire length of a single thick filament …. actin and myosin
H-zone Zone of the thick filaments that is not superimposed by the thin filaments… myosin only
M-line Middle of the sarcomere, cross-linking myosin
Z line - end of sarcomere
state the differences between type 1 and 2 skeletal muscle fibres.
Contraction time Slow (I) Fast (II)
Colour
Red (due to presence of myoglobin) (I)
White (due to absence of myoglobin) (I)
Main use Sustained force (I) Sudden movement (II)
Major fuel
Triglycerides (I)
ATP (II)
Mitochondrial density
High (I)
Low (II)
which diseases is nitric oxide implicated in?
underproduction of NO is implicated in hypertrophic pyloric stenosis
lack of NO is thought to promote atherosclerosis
in sepsis increased levels of NO contribute to septic shock
what is noonans syndrome?
normal karyotype
autosomal dominant
defect in chrom 12
often thought as - ‘male turners’
what are the features of noonans?
As well as features similar to Turner’s syndrome (webbed neck, widely-spaced nipples, short stature, pectus carinatum and excavatum), a number of characteristic clinical signs may also be seen:
cardiac: pulmonary valve stenosis
ptosis
triangular-shaped face
low-set ears
coagulation problems: factor XI deficiency
in a normal distribution what % of values lie within 1,2 and 3 SDs?
- 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
how are standard deviation and variance related?
SD = square root variance
what is the role of leptin?
leptin is produced by adipose tissue and acts on satiety centres in the hypothalamus and decreases appetite. More adipose tissue (e.g. in obesity) results in high leptin levels.
Leptin stimulates the release of melanocyte-stimulating hormone (MSH) and corticotrophin-releasing hormone (CRH). Low levels of leptin stimulates the release of neuropeptide Y (NPY)
what is the role of Ghrelin?
Ghrelin stimulates hunger. It is produced mainly by the P/D1 cells lining the fundus of the stomach and epsilon cells of the pancreas. Ghrelin levels increase before meals and decrease after meals
what is odds and odds ratios?
odds = no. of people where outcome did occur/ didnt occur
e.g. paracetamol pain relief in 40 people , but 20 people no pain relief (60 people in total)… 40/20 = 2
odds of 2
odds ratio = odds of drug / odds from placebo.
what are the following oncogenes implicated in ? ABL (BCR-ABL) cMYC nMYC BCL2
ABL tyrosine kinase Chronic myeloid leukaemia
c-MYC Transcription factor Burkitt’s lymphoma
n-MYC Transcription factor Neuroblastoma
BCL-2 Apoptosis regulator protein Follicular lymphoma
what are the following oncogenes implicated in ?
RET
RAS
ERB-B2 (HER2/neu)
RET Tyrosine kinase receptor
Multiple endocrine neoplasia (types II and III)
RAS G-protein
Many cancers especially pancreatic
erb-B2 (HER2/neu) Tyrosine kinase receptor Breast and ovarian cancer
is BRCA a tumour suppresor gene or oncogene?
TSG
what cancer is human herpes virus 8 associated with?
Kaposi’s sarcoma
what is HTLV1 virus associated with
Tropical spastic paraparesis
Adult T cell leukaemia
which cancers is p53 mutated in?
many.
its the most commonly mutated gene in breast, colon and lung cancer
what chromosome is p53 found on? what is its function?
17p
p53 is 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
in which genetic conditon is p53 mutated?
Li-Fraumeni syndrome
auto dominant
associated with many cancers
what is the difference between penetrance and expressivity?
Penetrance describes the proportion of a population of individuals who carry a disease-causing allele who express the related disease phenotype. The likelihood a condition will develop
Expressivity describes the extent to which a genotype shows its phenotypic expression in an individual. How severe a condition will be
what affects expressivity - i.e. why do two people carrying same gene expres to different levels?
Modifier genes
Environmental factors
Allelic variation
which gene is mutated in phenylketonuria (PKU)? what is the consequence?
phenylalanine hydroxylase (chrom 12), an enzyme which converts phenylalanine to tyrosine. phenylalanine builds up and can lead to toxic effects - learning difficulties and seizures.
what are the features of PKU?
usually presents by 6 months e.g. with developmental delay
child classically has fair hair and blue eyes
learning difficulties
seizures, typically infantile spasms
eczema
‘musty’ odour to urine and sweat*
how is PKU diagnosed?
Guthrie test: the ‘heel-prick’ test done at 5-9 days of life
hyperphenylalaninaemia
phenylpyruvic acid in urine
what are differences between type 1 and 2 pneumocytes?
type 1 - squamous cell, majority
type 2 - cuboidal, Secrete surfactant
Start to develop around 24 weeks gestation, however adequate surfactant production does not take place until around 35 weeks
what are club cells (a.k.a clara cells)
on-ciliated dome-shaped cells found in the bronchioles. They have a varied role including protecting against the deleterious effects of inhaled toxins and the secretion of glycosaminoglycans and lysozymes.
describe the process of PCR?
sample of DNA is added to the test tube along with two DNA primers
a thermostable DNA polymerase (Taq) is added
The following cycle then takes place
mixture is heated to almost boiling point causing denaturing (uncoiling) of DNA
mixture is then allowed to cool: complimentary strands of DNA pair up, as there is an excess of the primer sequences they pair with DNA preferentially
what is reverse transcriptase PCR?
Reverse transcriptase PCR
used to amplify RNA
RNA is converted to DNA by reverse transcriptase
what are the contents of the popliteal fossa?
Popliteal artery and vein Small saphenous vein Common peroneal nerve Tibial nerve Posterior cutaneous nerve of the thigh Genicular branch of the obturator nerve Lymph nodes
How are prader willi and angleman related?
examples of genetic imprinting
Prader-Willi syndrome if gene deleted from father
Angelman syndrome if gene deleted from mother
what is prader willi? (genetics)
Prader-Willi syndrome is associated with the absence of the active Prader-Willi gene on the long arm of chromosome 15. This may be due to:
microdeletion of paternal 15q11-13 (70% of cases)
maternal uniparental disomy of chromosome 15
what are the features of prader wili?
hypotonia during infancy childhood obesity dysmorphic features short stature hypogonadism and infertility learning difficulties behavioural problems in adolescence
what is pre-test probablity?
The proportion of people with the target disorder in the population at risk at a specific time (point prevalence) or time interval (period prevalence)
For example, the prevalence of rheumatoid arthritis in the UK is 1%
what is post test probablity?
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 are the pre-test odd?
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 are 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)
where is each kidney located?
on the anterior surface of psoas major.
In most cases the left kidney lies approximately 1.5cm higher than the right.
The upper pole of both kidneys approximates with the 11th rib (beware pneumothorax during nephrectomy). On the left hand side the hilum is located at the L1 vertebral level and the right kidney at level L1-2. The lower border of the kidneys is usually alongside L3.
which part of kidney is more at risk of ischaemia?
renal cortical blood flow > medullary blood flow (i.e. tubular cells more prone to ischaemia)
what is the glomerular filtration rate?
125ml/min
glomerular filtration rate = Total volume of plasma per unit time leaving the capillaries and entering the Bowman’s capsule
creatinine used to estimate this
(inulin can also be used - both inert, not absorbed/secreted, constant plasma conc, freely filtered)
what is renal clearance? (definition)
renal clearance = volume plasma from which a substance is removed per minute by the kidneys
what is the equation for GFR?
GFR = ( urine concentration (mmol/l) x urine volume (ml/min) ) / plasma concentration (mmol/l)
what is the most common renal stone?
calcium oxalate
what increases risk of caclium oxalate stone?
Hypercalciuria is a major risk factor (various causes)
Hyperoxaluria may also increase risk
Hypocitraturia
which stones are radiopaque?
calcium oxalate
calcium phosphate - the most opaque
cysteine
struvite
which stones are radiolucent?
uric acid stones
what causes cysteine stones?
Inherited recessive disorder of transmembrane cystine transport leading to decreased absorption of cystine from intestine and renal tubule
when do uric acid stones form?
high urate levels
when urinary pH low
May be caused by diseases with extensive tissue breakdown e.g. malignancy
More common in children with inborn errors of metabolism
when do calcium phosphate stones form?
May occur in renal tubular acidosis, high urinary pH increases supersaturation of urine with calcium and phosphate
what are struvite stones made from and how do they form?
Stones formed from magnesium, ammonium and phosphate
Occur as a result of urease producing bacteria
under alkaline conditions
what produces renin and what is the function of renin?
Renin is secreted by juxtaglomerular cells and hydrolyses angiotensinogen to produce angiotensin I
what increases and decreases renin production?
Factors stimulating renin secretion hypotension causing reduced renal perfusion hyponatraemia sympathetic nerve stimulation catecholamines erect posture
Factors reducing renin secretion
drugs: beta-blockers, NSAIDs
what do the different parts of adrenal cortex produce?
Adrenal cortex (mnemonic GFR - ACD)
zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone
zona fasciculata (middle): glucocorticoids, mainly cortisol
zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA)
what is the function of the enzyme ACE?
angiotensin-converting enzyme (ACE) in the lungs converts angiotensin I → angiotensin II
what are the functions of angiotensin II?
causes vasoconstriction of vascular smooth muscle leading to raised blood pressure and vasoconstriction of efferent arteriole of the glomerulus → increased filtration fraction (FF) to preserve GFR.
stimulates thirst (via the hypothalamus)
stimulates aldosterone and ADH release
increases proximal tubule Na+/H+ activity
what is the equation for filtration fraction?
FF = GFR / renal plasma flow
what releases aldosterone ? What is the function of aldoseterone?
released by the zona glomerulosa in response to raised angiotensin II, potassium, and ACTH levels
causes retention of Na+ in exchange for K+/H+ in distal tubule
what is lung compliance?
Lung compliance is defined as change in lung volume per unit change in airway pressure
what are the causes of increased and decreased lung compliance?
Causes of increased compliance
age
emphysema - this is due to loss alveolar walls and associated elastic tissue
Causes of decreased compliance pulmonary oedema pulmonary fibrosis pneumonectomy kyphosis
what is the relationship between mean/median/mode for negative/positive skewed distribution?
Positively skewed distribution: mean > median > mode
Negatively skewed distribution mean < median < mode
what are the stages of sleep?
Non-REM stage 1 (N1) Theta waves Light sleep
Transition to this stage be associated with hypnic jerks
Non-REM stage 2 (N2) Sleep spindles + K-complexes Deeper sleep
Represents around 50% of total sleep
Non-REM stage 3 (N3) Delta waves Deep sleep
Parasomnias such as night terrors, nocturnal enuresis, sleepwalking
REM Beta-waves Dreaming occurs
Loss of muscle tone, erections
pneumonic:
Theta → Sleep spindles/K-complexes → Delta → Beta
The Sleep Doctor’s Brain
where does the spinal cord start and end?
medulla oblongata of the brain
caudally it tapers at a level corresponding to the L1-2 interspace (in the adult), a central structure, the filum terminale anchors the cord to the first coccygeal vertebra.
what is brown sequard syndrome?
Brown- Sequard syndrome-Hemisection of the cord producing ipsilateral loss of proprioception and upper motor neurone signs, plus contralateral loss of pain and temperature sensation.
when do lesions start to show lower motor neuron signs (which level)?
After L1
what are the limitations of randomised control trial?
Practical or ethical problems may limit use
what is a cohort study?
Observational and prospective. Two (or more) are selected according to their exposure to a particular agent (e.g. medicine, toxin) and followed up to see how many develop a disease or other outcome.
The usual outcome measure is the relative risk.
Examples include Framingham Heart Study
what is a case control study? what are the pros and cons?
Observational and retrospective. Patients with a particular condition (cases) are identified and matched with controls. Data is then collected on past exposure to a possible causal agent for the condition.
The usual outcome measure is the odds ratio.
Inexpensive, produce quick results
Useful for studying rare conditions
Prone to confounding
whats a cross sectional study?
Provide a ‘snapshot’, sometimes called prevalence studies
Provide weak evidence of cause and effect
what are the different levels of evidence?
Grade A
Ia - evidence from meta-analysis of randomised controlled trials
Ib - evidence from at least one randomised controlled trial
GradeB
IIa - evidence from at least one well designed controlled trial which is not randomised
IIb - evidence from at least one well designed experimental trial
III - evidence from case, correlation and comparative studies
Grade C
IV - evidence from a panel of experts
