Clinical sciences Flashcards
(144 cards)
1
Q
How is left ventricular ejection fraction calculated?
A
Stroke Volume / End Diastolic Volume) × 100%
2
Q
What is a Wilcoxon signed-rank test?
A
compares two sets of observations on a single sample, e.g. a ‘before’ and ‘after’ test on the same population following an intervention
Non parametric
3
Q
What is a Mann Whitney U test?
A
compares ordinal, interval, or ratio scales of unpaired data
non parametric test
4
Q
What is a chi-squared test?
A
used to compare proportions or percentages e.g. compares the percentage of patients who improved following two different interventions
non parametric test
5
Q
What is a Spearman, Kendall rank test?
A
Used to assess correlation
Non parametric
6
Q
Which phase of the cell cycle determines cycle length?
A
G1 phase
7
Q
What occurs within G0 of the cell cycle?
A
‘resting’ phase
quiescent cells such as hepatocytes and more permanently resting cells such as neurons
8
Q
What occurs within G1 phase of cell cycle?
A
- Gap 1, cells increase in size
- determines length of cell cycle
- under influence of p53
9
Q
What occurs within G2 phase of cell cycle?
A
Gap 2, cells continue to increase in size
10
Q
What occurs within S phase of cell cycle?
A
Synthesis of DNA, RNA and histone
centrosome duplication
11
Q
What occurs within the M phase of the cell cycle?
A
Mitosis - cell division
the shortest phase of the cell cycle
12
Q
What type of receptor is an atrial natriuretic factor?
A
guanylate cyclase receptor
13
Q
Goodpasture’s syndrome is caused by autoantibodies against which substance?
A
type IV collagen
14
Q
What are the features and EEG findings of Non REM stage 1 sleep?
A
- Light sleep
- Transition to this stage be associated with hypnic jerks
- Theta waves on EEG
15
Q
What are the features and EEG findings of Non REM stage 2 sleep?
A
- Deeper sleep
- Represents around 50% of total sleep
- Sleep spindles + K-complexes on EEG
16
Q
What are the features and EGG findings of Non REM stage 3 sleep?
A
- Deep sleep
- Parasomnias such as night terrors, nocturnal enuresis, sleepwalking
- Delta waves on EEG
17
Q
What are the features and EEG findings of REM sleep?
A
- Dreaming occurs
- Loss of muscle tone, erections
- Beta waves on EEG
18
Q
What is the usual outcome in a cohort study?
A
Relative risk
19
Q
What are the features of randomised control trial?
A
Participants randomly allocated to intervention or control group (e.g. standard treatment or placebo)
Practical or ethical problems may limit use
20
Q
What are the features of a cohort study?
A
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
21
Q
What are the features of a case control study?
A
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
22
Q
What are the features of a cross sectional survey?
A
Provide a ‘snapshot’, sometimes called prevalence studies
Provide weak evidence of cause and effect
23
Q
What is the gold standard test for cerebral metastases?
A
MRI with contrast
24
Q
What are foam cells?
A
Fat-laden macrophages
25
Which clotting factors are inhibited by heparin?
Factors 2,9,10,11
26
Which clotting factors synthesis are affected by warfarin?
Factors 2,7,9,10
27
Which clotting factors are affected in DIC?
Factors 1,2,5,8,11
28
Which clotting factors are affected in liver disease?
Factors 1,2,5,7,9,10,11
29
What are the key features of haemophilia A?
X- linked recessive
Factor VIII
Intrinsic pathway affected
PT Normal
APTT prolonged (raised)
Deep tissue/joint bleeding
Severity correlates with factor level
Ix - APTT and factor VIII assay
Rx - Recombinant FVIII
30
What are the key features of haemophilia B?
X-linked recessive
Factor IX
Intrinsic pathway affected
PT Normal
APTT prolonged (raised)
Deep tissue/joint bleeding
Severity correlates with factor level
Ix - APTT, factor IX assay
Rx - Recombinant FIX
31
What are the key features of Von Willebrand disease?
Autosomal dominant
vWF ± Factor VIII
Platelet adhesion & intrinsic pathway affected
PT normal
APTT normal or prolonged
Prolonged bleeding time
Mucocutaneous (e.g. epistaxis, menorrhagia) bleeding
Variable severity
Ix - vWF antigen/activity + factor VIII assay
Rx - Desmopressin (Type 1), vWF concentrates
32
What are the key features of Factor XI deficiency?
Autosomal recessive (mainly Ashkenazi Jews)
Factor XI
Intrinsic pathway affected
PT normal
APTT prolonged
Variable bleeding (often post op)
Variable severity (often mild)
Ix - Isolated ↑ aPTT + factor XI assay
Rx - Antifibrinolytics ± FXI concentrate or FFP
33
What are the key features of Factor VII deficiency?
Autosomal recessive
Factor VII
Extrinsic pathway
PT prolonged
APTT normal
Mucocutaneous ± deep tissue bleeding
Variable severity (doesn't always correlate with factor levels)
Ix - isolated prolonged PT + factor VII assay
Rx - Recombinant FVIIa, plasma-derived FVII
34
What is achondroplasia?
Autosomal dominant disorder associated with short stature. It is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR-3) gene.
This leads to abnormal cartilage which results in:
- 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
35
What is the main risk factor for developing achondroplasia?
Advancing parental age at time of conception
36
What are the histopathological findings for acute tubular necrosis?
- tubular epithelium necrosis: loss of nuclei and detachment of tubular cells from the basement membrane
- dilatation of the tubules may occur
- necrotic cells obstruct the tubule lumen
37
What are the phases of acute tubular necrosis?
oliguric phase
polyuric phase
recovery phase
38
What is alkaptonuria?
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.
Eventually it accumulates in cartilage and other tissues.
39
What are the features of Alkaptonuria?
Generally a benign and often asymptomatic condition.
Features include:
- pigmented sclera
- urine turns black if left exposed to the air
- intervertebral disc calcification may result in back pain
- renal stones
40
What is the treatment for Alkaptonuria?
- high-dose vitamin C
- dietary restriction of phenylalanine and tyrosine
41
What is the function of anti-diuretic hormone?
Promotes water reabsorption in the collecting ducts of the kidneys by the insertion of aquaporin-2 channels.
42
What causes an increase in ADH secretion?
- extracellular fluid osmolality increase
- volume decrease
- pressure decrease
- angiotensin II
43
What causes a decrease in ADH secretion?
- extracellular fluid osmolality decrease
- volume increase
- temperature decrease
44
Where is ADH synthesised and released?
Synthesized in the supraoptic nuclei of the hypothalamus
Released by the posterior pituitary
45
What is meant by the term non-penetrance?
lack of clinical signs and symptoms (normal phenotype) despite abnormal gene. E.g. 40% otosclerosis
46
Which tumours most commonly spread to the brain?
lung (most common)
breast
bowel
skin (namely melanoma)
kidney
47
What is phase 0 of the cardiac cycle?
Rapid depolarisation
- rapid influx of sodium
48
What is phase 1 of the cardiac cycle?
Early repolarisation
- efflux of potassium
49
What is phase 2 of the cardiac cycle?
Plateau
- slow influx of calcium
50
What is phase 3 of the cardiac cycle?
Final repolarisation
- efflux of potassium
51
What is phase 4 of the cardiac cycle?
Restoration of ionic concentrations
- Resting potential is restored by Na+/K+ ATPase
There is slow entry of Na+ into the cell decreasing the potential difference until the threshold potential is reached, triggering a new action potential
52
What is stroke volume?
end diastolic LV volume - end systolic LV volume
53
What cardiac output?
Stroke volume x heart rate
Amount of blood pumped by heart in 1 minute
54
What is pulse pressure?
Systolic Pressure - Diastolic Pressure
55
What is systemic vascular resistance?
mean arterial pressure / cardiac output
56
What are the key features of mitosis?
- Occurs in somatic cells
- Results in 2 diploid daughter cells
- Daughter cells are genetically identical to parent cell.
57
What are the key features of meiosis?
- Occurs in gametes
- Results in 4 haploid daughter cells
- Daughter cells contain one homologue of each chromosome pair and are therefore genetically different
58
What are the features and action of atrial natriuretic 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 >> left)
- 28 amino acid peptide hormone, which acts via cGMP
- degraded by endopeptidases
Action:
- natriuretic, i.e. promotes excretion of sodium
- lowers BP
- antagonises actions of angiotensin II, aldosterone
59
What is selection bias?
Error in assigning individuals to groups leading to differences which may influence the outcome
60
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
- particular problem in case-control studies.
61
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.
62
What is work up (verification bias)?
In studies which compare new diagnostic tests with gold standard tests, work-up bias can be an issue. Sometimes clinicians may be reluctant to order the gold standard test unless the new test is positive, as the gold standard test may be invasive (e.g. tissue biopsy). This approach can seriously distort the results of a study, and alter values such as specificity and sensitivity.
Sometimes work-up bias cannot be avoided, in these cases it must be adjusted for by the researchers.
63
What is Expectation bias (Pygmalion effect)?
Only a problem in non-blinded trials. Observers may subconsciously measure or report data in a way that favours the expected study outcome.
64
What is Hawthorne effect?
Describes a group changing it's behaviour due to the knowledge that it is being studied
65
What is late-look bias?
Gathering information at an inappropriate time e.g. studying a fatal disease many years later when some of the patients may have died already
66
What is procedure bias?
Occurs when subjects in different groups receive different treatment
67
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
68
What are the features of glioblastoma multiforme?
Glioblastoma is the most common primary tumour in adults and is associated with a poor prognosis (~ 1yr).
- 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
- Treatment is surgical with postoperative chemotherapy and/or radiotherapy. Dexamethasone is used to treat the oedema.
69
What are the features of meningioma?
The second most common primary brain tumour in adults
- Meningiomas are typically benign, extrinsic tumours of the central nervous system. They arise from the arachnoid cap cells of the meninges and are typically located next to the dura and cause symptoms by compression rather than invasion.
-They typically are located at the falx cerebri, superior sagittal sinus, convexity or skull base.
-Histology: Spindle cells in concentric whorls and calcified psammoma bodies
- Investigation is with CT (will show contrast enhancement) and MRI, and treatment will involve either observation, radiotherapy or surgical resection.
70
What are the features of vestibular schwannomas?
A vestibular schwannoma (previously termed acoustic neuroma) is a benign tumour arising from the eighth cranial nerve (vestibulocochlear nerve). Often seen in the cerebellopontine angle. It presents with hearing loss, facial nerve palsy (due to compression of the nearby facial nerve) and tinnitus.
- Neurofibromatosis type 2 is associated with bilateral vestibular schwannomas.
- Histology: Antoni A or B patterns are seen. Verocay bodies (acellular areas surrounded by nuclear palisades)
- Treatment may involve observation, radiotherapy or surgery.
71
What are the features of pilocystic astrocytoma?
The most common primary brain tumour in children
- Histology: Rosenthal fibres (corkscrew eosinophilic bundle)
72
What are the features of medulloblastoma?
A medulloblastoma is an aggressive paediatric brain tumour that arises within the infratentorial compartment. It spreads through the CSF system
- Treatment is surgical resection and chemotherapy.
- Histology: Small, blue cells. Rosette pattern of cells with many mitotic figures
73
What are the features of ependymomas?
- Commonly seen in the 4th ventricle
- May cause hydrocephalus
- Histology: perivascular pseudorosettes
74
What are the features of oligodenromas?
- Benign, slow-growing tumour common in the frontal lobes
- Histology: Calcifications with 'fried-egg' appearance
75
What are the features of haemangioblastomas?
- Vascular tumour of the cerebellum
- Associated with von Hippel-Lindau syndrome
- Histology: foam cells and high vascularity
76
What are the features of pituitary adenomas?
Pituitary adenomas are benign tumours of the pituitary gland. They are either secretory (producing a hormone in excess) or non-secretory. They may be divided into microadenomas (smaller than 1cm) or macroadenoma (larger than 1cm).
- Patients will present with the consequences of hormone excess (e.g. Cushing's due to ACTH, or acromegaly due to GH) or depletion. - Compression of the optic chiasm will cause a bitemporal hemianopia due to the crossing nasal fibers.
- Investigation requires a pituitary blood profile and MRI.
- Treatment can either be hormonal or surgical (e.g. transphenoidal resection).
77
What are the features of craniopharyngiomas?
- Most common paediatric supratentorial tumour
- A craniopharyngioma is a solid/cystic tumour of the sellar region that is derived from the remnants of Rathke's pouch.
- It may present with hormonal disturbance, symptoms of hydrocephalus or bitemporal hemianopia.
- Histology: Derived from remnants of Rathke pouch
- Investigation requires pituitary blood profile and MRI.
- Treatment is typically surgical with or without postoperative radiotherapy.
78
What drugs are contraindicated in breastfeeding?
- antibiotics: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides
- psychiatric drugs: lithium, benzodiazepines
- aspirin
- carbimazole
- methotrexate
- sulfonylureas
- cytotoxic drugs
- amiodarone
79
What is the action of parathyroid hormone?
- 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
80
What is the action of 1,25(OH)2D (active form 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
81
What is the action of calcitonin?
- Secreted by C cells of thyroid
- Inhibits osteoclast activity
- Inhibits renal tubular absorption of calcium
82
What are the phases of mitosis?
Prometaphase: Nuclear membrane breaks down allowing the microtubules to attach to the chromosomes
Metaphase: Chromosomes aligned at middle of cell
Anaphase: The paired chromosomes separate at the kinetochores and move to opposite sides of the cell
Telophase: Chromatids arrive at opposite poles of cell
Cytokinesis: Actin-myosin complex in the centre of the cell contacts resulting in it being 'pinched' into two daughter cells
83
How is cerebral perfusion pressure calculated?
Mean arterial pressure - intracranial pressure
Might be tight controlled following head trauma.
84
What are the features of Patau syndrome (trisomy 13)?
Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions
85
What are the features of Edward's syndrome (trisomy 18)?
Micrognathia
Low-set ears
Rocker bottom feet
Overlapping of fingers
86
What are the features of fragile X syndrome?
Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism
87
What are the features of Noonan syndrome?
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis
88
What are the features of Pierre-Robin syndrome?
Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate
89
What are the features of Prader-Willi syndrome?
Hypotonia
Hypogonadism
Obesity
90
What are the features of William's syndrome?
Short stature
Learning difficulties
Friendly, extrovert personality
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis
91
What are the features of Cri du chat syndrome (chromosome 5p deletion syndrome)?
Characteristic cry (hence the name) due to larynx and neurological problems
Feeding difficulties and poor weight gain
Learning difficulties
Microcephaly and micrognathism
Hypertelorism
92
What is phase 0 of a clinical trial?
- Exploratory studies
- Involves a very small number of participants and aim to assess how a drug behaves in the human body. Used to assess pharmacokinetics and pharmacodynamics.
- Phase 0 trials help in determining whether it is feasible to move on to further phases.
93
What is phase I of a clinical trial?
- Safety assessment
- Determines side-effects prior to larger studies. Conducted on healthy volunteers
94
What is phase II of a clinical trial?
- Assess efficacy
- Involves small number of patients affected by particular disease
- May be subdivided into:
IIa - assesses optimal dosing
IIb - assesses efficacy
95
What is phase III of a clinical trial?
- Assess effectiveness
- Typically involves 100-1000's of people, often as part of a randomised controlled trial, comparing new treatment with established treatments
96
What is phase IV of a clinical trial?
- Post marketing surveillance
- Monitors for long-term effectiveness and side-effects
97
What are the features of Type I collagen?
Bone, skin, tendon
Associated with: Osteogenesis imperfecta
98
What are the features of Type II collagen?
Hyaline cartilage, vitreous humour
99
What are the features of type III collagen?
Reticular fibre, granulation tissue
Associated with: Vascular variant of Ehlers-Danlos syndrome
100
What are the features of type IV collagen?
Basal lamina, lens, basement membrane
Associated with: Alport syndrome (mutations in the genes encoding Type IV collagen), Goodpasture's syndrome (autoimmune reaction where antibodies attack the Type IV collagen)
101
What are the features of type V collagen?
Most interstitial tissue, placental tissue
Associated with: Classical variant of Ehlers-Danlos syndrome
102
What is a confidence interval?
a range of values within which the true effect of intervention is likely to lie
103
How is a confidence interval calculated?
A 95% confidence interval:
lower limit = mean - (1.96 * SEM)
upper limit = mean + (1.96 * SEM)
SEM = SD / square root (n)
104
What is confounding?
a variable which correlates with other variables within a study leading to spurious results.
can be controlled by randomisation which aims to produce an even amount of potential risk factors in two populations. In the analysis stage of an experiment, confounding can be controlled for by stratification.
105
What are the features of congenital infection with Rubella?
- Sensorineural deafness
- Congenital cataracts
- Congenital heart disease (e.g. patent ductus arteriosus)
- Glaucoma
Other features:
- Growth retardation
- Hepatosplenomegaly
- Purpuric skin lesions
- 'Salt and pepper' chorioretinitis
- Microphthalmia
- Cerebral palsy
106
What are the features of congenital toxoplasmosis infection?
- Cerebral calcification
- Chorioretinitis
- Hydrocephalus
Other features:
- Anaemia
- Hepatosplenomegaly
- Cerebral palsy
107
What is endothelin?
- Potent, long-acting vasoconstrictor and bronchoconstrictor
- secreted initially as a prohormone by the vascular endothelium and later converted to ET-1 by the action of endothelin converting enzyme.
- It acts via interaction with a G-protein linked to phospholipase C leading to calcium release.
- Endothelin is thought to be important in the pathogenesis of many diseases including primary pulmonary hypertension (endothelin antagonists are now used), cardiac failure, hepatorenal syndrome and Raynaud's.
108
What promotes the release of endothelin?
angiotensin II
ADH
hypoxia
mechanical shearing forces
109
What are the layers of the epidermis and what are they made of?
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
110
What is erythropoeisis?
Process through which red blood cells (erythrocytes) are produced. This occurs in 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.
111
What are the stages of erythropoiesis?
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
112
What is Fabry disease?
X-linked recessive
deficiency of alpha-galactosidase A
Features:
- burning pain/paraesthesia in childhood
- angiokeratomas
- lens opacities
- proteinuria
- early cardiovascular disease
113
Which drugs interfere with folate metabolism?
trimethoprim
methotrexate
pyrimethamine
114
Which drugs may reduce absorption of folate?
phenytoin
115
What is Fragile X syndrome?
Trinucleotide repeat disorder.
Features in males:
- learning difficulties
- large low set ears, long thin face, high arched palate
- macroorchidism
- hypotonia
- autism is more common
- mitral valve prolapse
Features in females (who have one fragile chromosome and one normal X chromosome) range from normal to mild
Diagnosis:
- can be made antenatally by chorionic villus sampling or amniocentesis
- analysis of the number of CGG repeats using restriction endonuclease digestion and Southern blot analysis
116
What is a funnel plot and how is it interpretted?
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.
Interpretation:
- a symmetrical, inverted funnel shape indicates that publication bias is unlikely
- conversely, an asymmetrical funnel indicates a relationship between treatment effect and study size. This indicates either publication bias or a systematic difference between smaller and larger studies ('small study effects')
117
Where is growth hormone produced?
Anterior pituitary: Somatotrophs comprise 50% of the cells of the anterior pituitary gland
118
What is the function of growth hormone?
- Postnatal growth and development
- Numerous actions on protein, carbohydrate and fat metabolism (including increasing lipolysis and gluconeogenesis)
119
What is the mechanism of action of growth hormone?
- Acts on a transmembrane receptor for growth factor
- Binding of GH to the receptor leads to receptor dimerization
- Acts directly on tissues and also indirectly via insulin-like growth factor 1 (IGF-1), primarily secreted by the liver
120
What increases secretion of growth hormone?
- growth hormone releasing hormone (GHRH): released in pulses by the hypothalamus
- fasting
- exercise
- sleep (particularly delta sleep)
121
What decreases secretion of growth hormone?
- Glucose
- somatostatin (itself increased by somatomedins, circulating insulin-like growth factors, IGF-1 and IGF-2)
122
What is the pathophysiology of HIV viral entry and initial infection?
- Target Cells: HIV primarily infects CD4+ T lymphocytes, macrophages, and dendritic cells.
- Attachment and Fusion: The viral envelope glycoproteins gp120 and gp41 facilitate attachment to the CD4 receptor and co-receptors (CCR5 or CXCR4) on host cells, enabling viral entry.
- Reverse Transcription and Integration: Once inside the host cell, reverse transcriptase converts viral RNA into proviral DNA, which integrates into the host genome via the integrase enzyme.
123
What are HIV's mechanisms of immune evasion?
- High Mutation Rate: Reverse transcriptase lacks proofreading ability, resulting in rapid genetic variability that allows the virus to evade immune detection.
- Glycan Shielding: Extensive glycosylation of gp120 masks viral epitopes from neutralising antibodies.
- Latency and Reservoirs: HIV establishes latent reservoirs in resting memory CD4+ T cells, evading both immune responses and antiretroviral therapy.
124
What is homocystinuria?
Rare autosomal recessive disease caused by a deficiency of cystathionine beta synthase.
Results in severe elevations in plasma and urine homocysteine concentrations.
125
What are the features of homocystinuria?
- often patients have fine, fair hair
- musculoskeletal
* Marfanoid body habitus: arachnodactyly etc
* osteoporosis
* kyphosis
- neurological: may have learning difficulties, seizures
- ocular
* downwards (inferonasal) dislocation of lens
* severe myopia
- increased risk of arterial and venous thromboembolism
- also malar flush, livedo reticularis
126
What are the investigations for homocystinuria?
- increased homocysteine levels in serum and urine
- cyanide-nitroprusside test: also positive in cystinuria
127
What is the management for homocystinuria?
vitamin B6 (pyridoxine) supplements.
128
What is the mechanism of a type 1 hypersensitivity reaction?
Antigen reacts with IgE bound to mast cells
e.g. anaphylaxis, atopy
129
What is the mechanism of a type II hypersensitivity reaction?
IgG or IgM binds to antigen on cell surface
e.g. Autoimmune haemolytic anaemia, ITP, Goodpasture's syndrome, Pernicious anaemia
130
What is the mechanism of a type III hypersensitivity reaction?
Free antigen and antibody (IgG, IgA) combine
e.g. Serum sickness, Systemic lupus erythematosus, Post-streptococcal glomerulonephritis
131
What is the mechanism of a type IV hypersensitivity reaction?
T-cell mediated
e.g. Tuberculosis / tuberculin skin reaction, Graft versus host disease, Allergic contact dermatitis, Scabies
132
What is the mechanism of a type V hypersensitivity reaction?
Antibodies that recognise and bind to the cell surface receptors.
This either stimulating them or blocking ligand binding
e.g. myasthenia gravis, Grave's disease
133
What are the functions and properties of helper T cells?
- Involved in the cell-mediated immune response
- Recognises antigens presented by MHC class II molecules
- Expresses CD4
- Also expresses CD3, TCR & CD28
- Major source of IL-2
- Mediates acute and chronic organ rejection
134
What are the functions and properties of cytotoxic T cells?
- Involved in the cell-mediated immune response
- Recognises antigens presented by MHC class I molecules
- Induce apoptosis in virally infected and tumour cells
- Expresses CD8
- Also expresses CD3, TCR
- Mediates acute and chronic organ rejection
135
What are the functions and properties of B cells?
- Major cell of the humoral immune response
- Acts as an antigen presenting cell
- Mediates hyperacute organ rejection
136
What are the functions and properties of plasma cells?
- Differentiated from B cells
- Produces large amounts of antibody specific to a particular antigen
137
What are the functions and properties of neutrophils?
- Primary phagocytic cell in acute inflammation
- Granules contain myeloperoxidase and lysozyme
- Most common type of white blood cell
- Multi-lobed nucleus
138
What are the function and properties of basophils?
- Releases histamine during allergic response
- Granules contain histamine and heparin
- Expresses IgE receptors on the cell surface
- Bi-lobed nucleus
139
What are the function and properties of mast cells?
- Present in tissues and are similar in function to basophils but derived from different cell lines
- Releases histamine during allergic response
- Granules contain histamine and heparin
- Expresses IgE receptors on the cell surface
140
What are the function and properties of eosinophils?
- Defends against protozoan and helminthic infections
- Bi-lobed nucleus
141
What are the functions and properties of monocytes?
- Differentiates into macrophages
- Kidney shaped nucleus
142
What are the functions and properties of macrophages?
- Involved in phagocytosis of cellular debris and pathogens
- Acts as an antigen presenting cell
- Major source of IL-1
143
What are the functions and properties of natural killer cells?
Induce apoptosis in virally infected and tumour cells
144
