Basic science Flashcards

1
Q

eGFR equation

A

GFR = ( urine concentration (mmol/l) x urine volume (ml/min) ) / plasma concentration (mmol/l)

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2
Q

MA of RCTs level of evidence

A

Ia

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3
Q

RCT level of evidence

A

1b

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4
Q

Control trial, not randomised level of evidence

A

2a

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5
Q

2b level of evidence

A

evidence from at least one well designed experimental trial

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6
Q

3 level of evidence

A

evidence from case, correlation and comparative studies

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7
Q

4 level of evidence

A

evidence from a panel of experts

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8
Q

what regulates cell cycle

A

proteins called cyclins which in turn control cyclin-dependent kinase (CDK) enzymes.

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9
Q

phases of cell cycle

A

G0,G1,S,G2,M

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10
Q

G0

A

‘resting’ phase

quiescent cells such as hepatocytes and more permanently resting cells such as neurons

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11
Q

G1

A

Gap 1, cells increase in size
determines length of cell cycle
under influence of p53

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12
Q

regulatory proteins G1

A

Cyclin D / CDK4, Cyclin D / CDK6 and Cyclin E / CDK2: regulates transition from G1 to S phase

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13
Q

S

A

Synthesis of DNA, RNA and histone

centrosome duplication

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14
Q

regulatory proteins S

A

Cyclin A / CDK2: active in S phase

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15
Q

G2

A

Gap 2, cells continue to increase in size

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16
Q

regulatory preoteins G2

A

Cyclin B / CDK1: regulates transition from G2 to M phase

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17
Q

M

A

Mitosis - cell division

the shortest phase of the cell cycle

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18
Q

negative predictive value equation

A

TN / (TN + FN)

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19
Q

sensitivity equation

A

TP / (TP + FN )

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20
Q

specificity equation

A

TN / (TN + FP)

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21
Q

PPV equation

A

TP / (TP + FP)

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22
Q

likelihood ratio for a positive result

A

sensitivity / (1 - specificity)

How much the odds of the disease increase when a test is positive

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23
Q

likelihood ratio negative test

A

(1 - sensitivity) / specificity

How much the odds of the disease decrease when a test is negative

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24
Q

most common congenital infection in the UK

A

CMV

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25
``` Sensorineural deafness Congenital cataracts Congenital heart disease (e.g. patent ductus arteriosus) Glaucoma congenital infection ```
rubella
26
Cerebral calcification Chorioretinitis Hydrocephalus congenital infection
toxoplasmosis
27
Growth retardation Purpuric skin lesions congenital infection
CMV
28
audit definition
a quality improvement process that seeks to improve patient care and outcomes through systematic review of care against explicit criteria and the implementation of change
29
what phase of mitosis does vincristine act on?
metaphase These drugs bind to tubulin stopping the polymerisation and assembly of microtubules. This, in turn, disrupts spindle formation arresting mitosis at metaphase.
30
what happens in prophase
Chromatin in the nucleus condenses
31
prometaphase
Nuclear membrane breaks down allowing the microtubules to attach to the chromosomes
32
metaphase
Chromosomes aligned at middle of cell
33
anaphase
The paired chromosomes separate at the kinetochores and move to opposite sides of the cell
34
telophase
Chromatids arrive at opposite poles of cell
35
cytokinesis
Actin-myosin complex in the centre of the cell contacts resulting in it being 'pinched' into two daughter cells
36
parametric tests
Student's t-test - paired or unpaired* | Pearson's product-moment coefficient - correlation
37
non-parametric tests
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
38
what are compliment
series of proteins that circulate in plasma and are involved in the inflammatory and immune reaction of the body. Complement proteins are involved in chemotaxis, cell lysis and opsonisation
39
C1 deficiency
``` C1 inhibitor (C1-INH) protein deficiency causes hereditary angioedema C1-INH is a multifunctional serine protease inhibitor probable mechanism is uncontrolled release of bradykinin resulting in oedema of tissues ```
40
classical pathway compliment and deficiency
C1q, C1rs, C2, C4 deficiency (classical pathway components) predisposes to immune complex disease e.g. SLE, Henoch-Schonlein Purpura
41
c3 deficiency
predisposes to bacterial infections
42
C5 deficiency
predisposes to Leiner disease | recurrent diarrhoea, wasting and seborrhoeic dermatitis
43
C5-9 deficiency
encodes the membrane attack complex (MAC) | particularly prone to Neisseria meningitidis infection
44
IL-1 source and functions
Macrophages Acute inflammation | Induces fever
45
IL-2 source and functions
Th1 cells Stimulates growth and differentiation of T cell response
46
IL-3 source and functions
Activated T helper cells Stimulates differentiation and proliferation of myeloid progenitor cells
47
IL-4 source and functions
Th2 cells Stimulates proliferation and differentiation of B cells
48
IL-5 source and functions
Th2 cells Stimulate production of eosinophils
49
IL-6 source and functions
Macrophages, Th2 cells Stimulates differentiation of B cells | Induces fever
50
IL-8 source and functions
Macrophages Neutrophil chemotaxis
51
IL-10 source and functions
Th2 cells Inhibits Th1 cytokine production Also known as human cytokine synthesis inhibitory factor and is an 'anti-inflammatory' cytokine
52
IL-12 source and functions
Dendritic cells, macrophages, B cells | Activates NK cells and stimulates differentiation of naive T cells into Th1 cells
53
TNF alpha source and functions
Macrophages Induces fever | Neutrophil chemotaxis
54
interferon Y source and functions
Th1 cells Activates macrophages
55
type 1 error
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. This is determined against a preset significance level (termed alpha). As the significance level is determined in advance the chance of making a type I error is not affected by sample size. It is however increased if the number of end-points are increased. For example if a study has 20 end-points it is likely one of these will be reached, just by chance.
56
type 2 error
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
57
define the power of a study
the probability of (correctly) rejecting the null hypothesis when it is false, i.e. the probability of detecting a statistically significant difference power = 1 - the probability of a type II error power can be increased by increasing the sample size
58
what is atrial nartiuretic 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
59
effects of ANP
natriuretic, i.e. promotes excretion of sodium lowers BP antagonises actions of angiotensin II, aldosterone
60
artherosclerosis stages
initial endothelial dysfunction is triggered by a number of factors such as smoking, hypertension and hyperglycaemia this results in a number of changes to the endothelium including pro-inflammatory, pro-oxidant, proliferative and reduced nitric oxide bioavailability fatty infiltration of the subendothelial space by low-density lipoprotein (LDL) particles monocytes migrate from the blood and differentiate into macrophages. These macrophages then phagocytose oxidized LDL, slowly turning into large 'foam cells'. As these macrophages die the result can further propagate the inflammatory process. smooth muscle proliferation and migration from the tunica media into the intima results in formation of a fibrous capsule covering the fatty plaque.
61
artherosclerosis complications
the plaque forms a physical blockage in the lumen of the coronary artery. This may cause reduced blood flow and hence oxygen to the myocardium, particularly at times of increased demand, resulting clinically in angina the plaque may rupture, potentially causing a complete occlusion of the coronary artery. This may result in a myocardial infarction
62
what is p53
p53 is a tumour suppressor gene located on chromosome 17p. It is the most commonly mutated gene in breast, colon and lung cancer. 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
63
what is Li-fraumeni syndrome?
rare autosomal dominant disorder characterised by the early onset of a variety of cancers such as sarcoma, breast cancer and leukaemias. It is caused by mutation in the p53 gene.
64
vitamin D function
increases plasma calcium and plasma phosphate increases renal tubular reabsorption and gut absorption of calcium increases osteoclastic activity increases renal phosphate reabsorption
65
vitamin d deficiency causes
rickets: seen in children osteomalacia: seen in adults
66
cerebral metastasis features
Metastatic brain cancer is the most common form of brain tumours. They are often multiple and not treatable with surgical intervention. ``` Tumours that most commonly spread to the brain include: lung (most common) breast bowel skin (namely melanoma) kidney ```
67
glioblastoma features
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.
68
meningioma features
The second most common primary brain tumour in adults * 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. * 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.
69
schwannoma features
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.
70
pilocytic astrocytoma features
The most common primary brain tumour in children | • Histology: Rosenthal fibres (corkscrew eosinophilic bundle)
71
medulloblastoma features
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
72
ependymoma features
* Commonly seen in the 4th ventricle * May cause hydrocephalus * Histology: perivascular pseudorosettes
73
oligodendroma features
Benign, slow-growing tumour common in the frontal lobes | • Histology: Calcifications with 'fried-egg' appearance
74
haemangioblastoma features
* Vascular tumour of the cerebellum * Associated with von Hippel-Lindau syndrome * Histology: foam cells and high vascularity
75
pituitary adenoma features
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).
76
craniopharyngioma features
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 is common in children, but can present in adults also. 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.
77
vitamin c functions
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
78
vitamin c deficiency features
gingivitis, loose teeth poor wound healing bleeding from gums, haematuria, epistaxis general malaise
79
what is fragile X?
trinucleotide repeat disorder
80
fragile X features
``` 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
81
equation for standard error mean
SEM = SD / square root (n) where SD = standard deviation and n = sample size therefore the SEM gets smaller as the sample size (n) increases
82
95% confidence interval equation
lower limit = mean - (1.96 * SEM) | upper limit = mean + (1.96 * SEM)
83
collagen structure
Composed of 3 polypeptide strands that are woven into a helix, usually a combination of glycine with either proline or hydroxyproline plus another amino acid Numerous hydrogen bonds exist within molecule to provide additional strength Many subtypes but commonest subtype is I (90% of bodily collagen), tissues with increased levels of flexibility have increased levels of type III collagen Vitamin C is important in establishing cross-links Synthesised by fibroblasts
84
where is type 1 collagen found and what are the associated conditions?
Bone, skin, tendon Osteogenesis imperfecta
85
where is type 2 collagen found ?
Hyaline cartilage, vitreous humour
86
where is type 3 collagen found and what are the associated conditions?
Reticular fibre, granulation tissue Vascular variant of Ehlers-Danlos syndrome
87
where is type 4 collagen found and what are the associated conditions?
Basal lamina, lens, basement membrane Alport syndrome, Goodpasture's syndrome
88
where is type 5 collagen found and what are the associated conditions?
Most interstitial tissue, placental tissue Classical variant of Ehlers-Danlos syndrome
89
dry beriberi
B1 (thiamine deficiency) | peripheral neuropathy
90
wet beriberi
B1 (thiamine deficiency) | dilated cardiomyopathy
91
causes of thiamine deficiency
alcohol excess. Thiamine supplements are the only routinely recommend supplement in patients with alcoholism malnutrition
92
LVEF equation
Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) * 100%
93
stroke volume equation
Stroke volume = end diastolic LV volume - end systolic LV volume
94
factors which increase pulse pressure
a less compliant aorta (this tends to occur with advancing age) increased stroke volume
95
systemic vascular resistance calculation
Systemic vascular resistance = mean arterial pressure / cardiac output
96
vitamin k dependent clotting factors
II, VII, IX, X
97
how are oncogenes different from tumor supressor genes?
Tumor suppressor genes - loss of function results in an increased risk of cancer Oncogenes - gain of function results in an increased risk of cancer
98
CML associated gene
ABL | Cytoplasmic tyrosine kinase
99
Burkitt's lymphoma associated gene
c-MYC Transcription factor
100
neuroblastoma associated gene
n-MYC Transcription factor
101
follicular lymphoma associated gene
BCL-2 Apoptosis regulator protein
102
MEN 2+3 gene
RET Tyrosine kinase receptor
103
RAS gene conditions
G-protein Many cancers especially pancreatic
104
erb-B2 associated cancer
erb-B2 (HER2/neu) Tyrosine kinase receptor Breast and ovarian cancer
105
ADH secreted from?
Synthesized in the supraoptic nuclei of the hypothalamus, released by the posterior pituitary
106
ADH function
Conserves body water Promotes water reabsorption in the collecting ducts of the kidneys by the insertion of aquaporin-2 channels
107
ADH regulation
``` Increases secretion extracellular fluid osmolality increase volume decrease pressure decrease angiotensin II ``` Decreases secretion extracellular fluid osmolality decrease volume increase temperature decrease Diabetes insipidus (DI) is a condition characterised by either a deficiency of antidiuretic hormone, ADH, (cranial DI) or an insensitivity to antidiuretic hormone (nephrogenic DI) Cranial DI can be treated by desmopressin, an analog of ADH
108
Di George syndrome cause
T-cell deficiency and dysfunction. It is an example of a microdeletion syndrome (deletion of a section of chromosome 22).
109
Di George syndrome features
``` C - Cardiac abnormalities A - Abnormal facies T - Thymic aplasia C - Cleft palate H - Hypocalcaemia/ hypoparathyroidism (parathyroid gland hypoplasia) 22 - Caused by chromosome 22 deletion ```
110
what infection are patients with t-cell dysfunction at risk of
recurrent viral and fungal infections | e.g. cryptococcus
111
homocystinuria features
often patients have fine, fair hair musculoskeletal: may be similar to Marfan's - arachnodactyly etc neurological patients may have learning difficulties, seizures ocular: downwards (inferonasal) dislocation of lens increased risk of arterial and venous thromboembolism also malar flush, livedo reticularis
112
homocystinuria diagnosis
cyanide-nitroprusside test, which is also positive in cystinuria.
113
homocystinuria cause
rare autosomal recessive disease caused by a deficiency of cystathionine beta synthase. This results in severe elevations in plasma and urine homocysteine concentrations.
114
homocystinuria treatment
vitamin B6 (pyridoxine)
115
southern blotting detects
DNA SNOW DROP
116
northern blotting detects
RNA SNOW DROP
117
Western blotting detects
proteins Uses gel electrophoresis to separate native proteins by 3-D structure Examples include the confirmatory HIV test SNOW DROP
118
what is ELISA?
a type of biochemical assay used to detect antigens and antibodies a colour changing enzyme is attached to the antibody if looking for an antigen and to an antigen if looking for an antibody the sample therefore changes colour if the antigen or antibody is detected an example includes the initial HIV test
119
4 main types of membrane receptor
- ligand gated ion channels - tyrosine kinase receptors - guanylate cyclase receptors - GPCRS
120
ligand-gated ion channel receptors
generally mediate fast responses | e.g. nicotinic acetylcholine, GABA-A & GABA-C, glutamate receptors
121
tyrosine kinase receptors
receptor tyrosine kinase: insulin, insulin-like growth factor (IGF), epidermal growth factor (EGF) non-receptor tyrosine kinase: PIGG(L)ET: Prolactin, Immunomodulators (cytokines IL-2, Il-6, IFN), GH, G-CSF, Erythropoietin and Thromobopoietin
122
guanylate cyclase receptors
contain intrinsic enzyme activity | e.g. atrial natriuretic factor, brain natriuretic peptide
123
GPCRS
generally mediate slow transmission and affect metabolic processes activated by a wide variety of extracellular signals e.g. Peptide hormones, biogenic amines (e.g. adrenaline), lipophilic hormones, light 7-helix membrane-spanning domains consist of 3 main subunits: alpha, beta and gamma the alpha subunit is linked to GDP.Ligand binding causes conformational changes to receptor, GDP is phosphorylated to GTP,and the alpha subunit is activated G proteins are named according to the alpha subunit (Gs, Gi, Gq)
124
what does Gs do?
Stimulates adenylate cyclase → increases cAMP → activates protein kinase A Beta-1 receptors (epinephrine, norepinephrine, dobutamine) • Beta-2 receptors (epinephrine, salbuterol) • H2 receptors (histamine) • D1 receptors (dopamine) • V2 receptors (vasopressin) • Receptors for ACTH, LH, FSH, glucagon, PTH, calcitonin, prostaglandins
125
what does Gi do?
Inhibits adenylate cyclase → decreases cAMP → inhibits protein kinase A M2 receptors (acetylcholine) • Alpha-2 receptors (epinephrine, norephinephrine) • D2 receptors (dopamine) • GABA-B receptor
126
what does Gq do?
Activates phospholipase C → splits PIP2 to IP3 & DAG → activates protein kinase C Alpha-1 receptors (epinephrine, norepinephrine) • H1 receptors (histamine) • V1 receptors (vasopressin) • M1, M3 receptors (acetylcholine)
127
Type 1 hypersensitivity reaction
Antigen reacts with IgE bound to mast cells • Anaphylaxis | • Atopy (e.g. asthma, eczema and hayfever)
128
Type 2 hypersensitivity reaction
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
129
type 3 hypersensitivity
Type III - Immune complex Free antigen and antibody (IgG, IgA) combine • Serum sickness • Systemic lupus erythematosus • Post-streptococcal glomerulonephritis • Extrinsic allergic alveolitis (especially acute phase)
130
Type 4 hypersensitivity reaction
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
131
Type 5 hypersensitivity reaction
Antibodies that recognise and bind to the cell surface receptors. This either stimulating them or blocking ligand binding • Graves' disease • Myasthenia gravis
132
Ulnar nerve motor to...
``` medial two lumbricals aDductor pollicis interossei hypothenar muscles: abductor digiti minimi, flexor digiti minimi flexor carpi ulnaris ```
133
Down's syndrome features
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
134
Down's syndrome cardiac defects
multiple cardiac problems may be present 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%)
135
later complications of Down's
``` subfertility: males are almost always infertile due to impaired spermatogenesis. Females are usually subfertile, and have an increased incidence of problems with pregnancy and labour learning difficulties short stature repeated respiratory infections (+hearing impairment from glue ear) acute lymphoblastic leukaemia hypothyroidism Alzheimer's disease atlantoaxial instability ```
136
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
Gaucher's disease
137
cherry red spots on macula, normal liver
Tay-Sachs disease Hexosaminidase A 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)
138
cherry red spots on macula, enlarged liver
Niemann-Pick disease Sphingomyelinase Key features include hepatosplenomegaly, cherry red spot on the macula
139
NNT
1 / (control event rate - experimental event rate) OR 1 / Absolute Risk Reduction
140
Turners syndrome features
short stature shield chest, widely spaced nipples webbed neck bicuspid aortic valve (15%), coarctation of the aorta (5-10%) primary amenorrhoea cystic hygroma (often diagnosed prenatally) high-arched palate short fourth metacarpal multiple pigmented naevi lymphoedema in neonates (especially feet) gonadotrophin levels will be elevated hypothyroidism is much more common in Turner's horseshoe kidney: the most common renal abnormality in Turner's syndrome There is also an increased incidence of autoimmune disease (especially autoimmune thyroiditis) and Crohn's disease
141
turners syndrome pathophysiology
It is caused by either the presence of only one sex chromosome (X) or a deletion of the short arm of one of the X chromosomes. Turner's syndrome is denoted as 45,XO or 45,X.
142
down's syndrome genetics
94% Nondisjunction 5% Robertsonian translocation 1% mosaicism
143
Raised PAPP-A and abnormal nuchal translucency
Down's syndrome
144
trinucleotide repeat disorders
``` Fragile X (CGG) Huntington's (CAG) myotonic dystrophy (CTG) Friedreich's ataxia* (GAA) spinocerebellar ataxia spinobulbar muscular atrophy dentatorubral pallidoluysian atrophy ``` *Friedreich's ataxia is unusual in not demonstrating anticipation
145
PTH actions
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
146
1,25 dihydroxycholecalciferol effects
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
147
Calcitonin effects
Secreted by C cells of thyroid Inhibits osteoclast activity Inhibits renal tubular absorption of calcium
148
Which drug for TB can cause burning in the feet?
Isoniazid therapy can cause a vitamin B6 deficiency causing peripheral neuropathy
149
Vitamin B6 deficincy consequences
peripheral neuropathy | sideroblastic anaemia
150
Noonan's syndrome
'male Turner's', Noonan syndrome is an autosomal dominant condition associated with a normal karyotype. It is thought to be caused by a defect in a gene on chromosome 12 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
151
role of T helper 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
152
role 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
153
role of B cells
Major cell of the humoral immune response Acts as an antigen presenting cell Mediates hyperacute organ rejection
154
role of plasma cells
Differentiated from B cells | Produces large amounts of antibody specific to a particular antigen
155
Wilson and Junger screening criteria
1. The condition should be an important public health problem 2. There should be an acceptable treatment for patients with recognised disease 3. Facilities for diagnosis and treatment should be available 4. There should be a recognised latent or early symptomatic stage 5. The natural history of the condition, including its development from latent to declared disease should be adequately understood 6. There should be a suitable test or examination 7. The test or examination should be acceptable to the population 8. There should be agreed policy on whom to treat 9. The cost of case-finding (including diagnosis and subsequent treatment of patients) should be economically balanced in relation to the possible expenditure as a whole 10. Case-finding should be a continuous process and not a 'once and for all' project
156
Blood tests in DIC
prolonged clotting times, thrombocytopenia, decreased fibrinogen, increased fibrinogen degradation products
157
Causes of DIC
``` Infection Malignancy Trauma e.g. major surgery, burns, shock, dissecting aortic aneurysm Liver disease Obstetric complications ```
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Haemophillia inheritance
In X-linked recessive inheritance only males are affected. An exception to this seen in examinations are patients with Turner's syndrome, who are affected due to only having one X chromosome. X-linked recessive disorders are transmitted by heterozygote females (carriers) and male-to-male transmission is not seen. Affected males can only have unaffected sons and carrier daughters. Each male child of a heterozygous female carrier has a 50% chance of being affected whilst each female child of a heterozygous female carrier has a 50% chance of being a carrier. The possibility of an affected father having children with a heterozygous female carrier is generally speaking extremely rare. However, in certain Afro-Caribbean communities G6PD deficiency is relatively common and homozygous females with clinical manifestations of the enzyme defect are seen.
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Cardiac cycle stages
0 Rapid depolarisation 1 Early repolarisation 2 Plateau 3 Final repolarisation 4 Restoration of ionic concentrations
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what causes phase 0 of cardiac cycle?
Rapid sodium influx | These channels automatically deactivate after a few ms
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what causes phase 1 of cardiac cycle?
Efflux of potassium
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what causes phase 2 of cardiac cycle?
Slow influx of calcium
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what causes phase 3 of cardiac cycle?
Efflux of potassium
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what causes phase 4 of cardiac cycle?
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
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define penetrance
Penetrance describes the proportion of a population of individuals who carry a disease-causing allele who express the related disease phenotype.
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define expressivity
Expressivity describes the extent to which a genotype shows its phenotypic expression in an individual. These phenomena are thought to be due to a number of factors, including: Modifier genes Environmental factors Allelic variation
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PKU features
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*
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PKU pathophysiology
autosomal recessive condition caused by a disorder of phenylalanine metabolism. This is usually due to defect in phenylalanine hydroxylase, an enzyme which converts phenylalanine to tyrosine. In a small number of cases the underlying defect is a deficiency of the tetrahydrobiopterin-deficient cofactor, e.g. secondary to defective dihydrobiopterin reductase. High levels of phenylalanine lead to problems such as learning difficulties and seizures. The gene for phenylalanine hydroxylase is located on chromosome 12. The incidence of PKU is around 1 in 10,000 live births.
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PKU diagnosis
Guthrie test: the 'heel-prick' test done at 5-9 days of life - also looks for other biochemical disorders such as hypothyroidism hyperphenylalaninaemia phenylpyruvic acid in urine
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PKU management
poor evidence base to suggest strict diet prevents learning disabilities dietary restrictions are however important during pregnancy as genetically normal fetuses may be affected by high maternal phenylalanine levels
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Bohr effect
increasing acidity (or pCO2) means O2 binds less well to Hb
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Haldane effect
increase pO2 means CO2 binds less well to Hb
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main functioning component of surfactant
dipalmitoyl phosphatidylcholine (DPPC) which reduces alveolar surface tension.
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surfactant released by...
type 2 pneumocytes
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Relative risk reduction
(EER - CER) / CER
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Relative risk ratio
EER / CER
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corneal reflexes nerves
Ophthalmic nerve (V1) Facial nerve (VII)
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Jaw jerk reflex
Mandibular nerve (V3) Mandibular nerve (V3)
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Gag reflex nerves
Glossopharyngeal nerve (IX) Vagal nerve (X)
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carotid sinus nerve
Glossopharyngeal nerve (IX) Vagal nerve (X)
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pupillary light reflex nerve
Optic nerve (II) Oculomotor nerve (III)
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lacrimation reflex nerves
Ophthalmic nerve (V1) Facial nerve (VII)
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define p value
is the probability of obtaining a result by chance at least as extreme as the one that was actually observed, assuming that the null hypothesis is true
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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. Alkaptonuria is generally a benign and often asymptomatic condition. Possible features include: pigmented sclera urine turns black if left exposed to the air intervertebral disc calcification may result in back pain renal stones Treatment high-dose vitamin C dietary restriction of phenylalanine and tyrosine
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nitric oxide effects
acts on guanylate cyclase leading to raised intracellular cGMP levels and therefore decreasing Ca2+ levels vasodilation, mainly venodilation inhibits platelet aggregation
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clinical relevance NO
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 organic nitrates (metabolism produces NO) is widely used to treat cardiovascular disease (e.g. angina, heart failure) sildenafil is thought to potentiate the action of NO on penile smooth muscle and is used in the treatment of erectile dysfunctions
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Linear regression
In contrast to the correlation coefficient, linear regression may be used to predict how much one variable changes when a second variable is changed. A regression equation may be formed, y = a + bx, where y = the variable being calculated a = the intercept value, when x = 0 b = the slope of the line or regression coefficient. Simply put, how much y changes for a given change in x x = the second variable
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IgG
75% Monomer • Enhance phagocytosis of bacteria and viruses • Fixes complement and passes to the fetal circulation • Most abundant isotype in blood serum GAMDE
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IgA
15% Monomer/ dimer • IgA is the predominant immunoglobulin found in breast milk. It is also found in the secretions of digestive, respiratory and urogenital tracts and systems • Provides localized protection on mucous membranes • Most commonly produced immunoglobulin in the body (but blood serum concentrations lower than IgG .) • Transported across the interior of the cell via transcytosis
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IgM
10% Pentamer • First immunoglobulins to be secreted in response to an infection • Fixes complement but does not pass to the fetal circulation • Anti-A, B blood antibodies (note how they cannot pass to the fetal circulation, which could of course result in haemolysis) Pentamer when secreted
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IgD
1% Monomer • Role in immune system largely unknown | • Involved in activation of B cells
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IgE
0.1% Monomer • Mediates type 1 hypersensitivity reactions • Binds to Fc receptors found on the surface of mast cells and basophils • Provides immunity to parasites such as helminths • Least abundant isotype in blood serum
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types of T cells
Th1 and Th2
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Th1 cells do what
involved in the cell-mediated response and delayed (type IV) hypersensitivity secrete IFN-gamma, IL-2, IL-3
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Th2 cells do what
involved in mediating humoral (antibody) immunity e.g. stimulating production of IgE in asthma secrete IL-4, IL-5, IL-6, IL-10, IL-13
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Endothelin
Endothelin is a potent, long-acting vasoconstrictor and bronchoconstrictor. It is 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 ``` Promotes release angiotensin II ADH hypoxia mechanical shearing forces ``` Inhibits release nitric oxide prostacyclin ``` Raised levels in MI heart failure ARF asthma primary pulmonary hypertension ```
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funnel plot use
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')
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Immunological changes 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 ```
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5 epidermal layers
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 ``` Come (corneum) Let's (lucidum) Get (granulosum) Sun (spinosum) Burnt (basale) ```
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Skeletal muscle contraction
action potential reaches the neuromuscular junction, causing a calcium ion influx through voltage-gated calcium channels the calcium influx causes the release of acetylcholine into the extracellular space the acetylcholine activates nicotinic acetylcholine receptors causing an influx of sodium, triggering an action potential the action potential spreads through the T-tubules the depolarization activates L-type voltage-dependent calcium channels (dihydropyridine receptors) in the T-tubule membrane, which are close to calcium-release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum this causes the sarcoplasmic reticulum to release calcium calcium 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
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Fabry's disease
Overview X-linked recessive deficiency of alpha-galactosidase A ``` Features burning pain/paraesthesia in childhood angiokeratomas lens opacities proteinuria early cardiovascular disease ```
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Leptin
Leptin is thought to play a key role in the regulation of body weight. It 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)
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Ghrelin
Where as leptin induces satiety, 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
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odds ratio
ad/bc
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causes of metabolic alkalosis
``` vomiting / aspiration (e.g. peptic ulcer leading to pyloric stenos, nasogastric suction) diuretics liquorice, carbenoxolone hypokalaemia primary hyperaldosteronism Cushing's syndrome Bartter's syndrome ```
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mechanism of metabolic alkalosis
``` activation of renin-angiotensin II-aldosterone (RAA) system is a key factor aldosterone causes reabsorption of Na+ in exchange for H+ in the distal convoluted tubule ECF depletion (vomiting, diuretics) → Na+ and Cl- loss → activation of RAA system → raised aldosterone levels in hypokalaemia, K+ shift from cells → ECF, alkalosis is caused by shift of H+ into cells to maintain neutrality ```
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superiority trial
superiority: whilst this may seem the natural aim of a trial one problem is the large sample size needed to show a significant benefit over an existing treatment
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equivalence trial
an equivalence margin is defined (-delta to +delta) on a specified outcome. If the confidence interval of the difference between the two drugs lies within the equivalence margin then the drugs may be assumed to have a similar effect
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non-inferiority trial
similar to equivalence trials, but only the lower confidence interval needs to lie within the equivalence margin (i.e. -delta). Small sample sizes are needed for these trials. Once a drug has been shown to be non-inferior large studies may be performed to show superiority
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drugs contraindicated in breast feeding
``` antibiotics: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides psychiatric drugs: lithium, benzodiazepines aspirin carbimazole methotrexate sulfonylureas cytotoxic drugs amiodarone ```
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skewed distribution
alphabetical order: mean - median - mode | '>' for positive, '
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function of microtubules
Microtubules are components of the cytoskeleton of the cytoplasm. They help guide movement during intracellular transport and also help bind internal organelles. Microtubules are found in all cells except red blood cells.
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microtubules structure
cylindrical structure composed of alternating α and β tubulin subunits which polymerize to form protofilaments microtubules are polarized, having a positive and negative end
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molecular transport microtubules
attachment proteins called dynein and kinesin move up and down the microtubules facilitating the movement of various organelles around the cell dynein moves in a retrograde fashion, down the the microtubule towards the centre of the cell (+ve → -ve) kinesin moves in an anterograde fashion, up the microtubule away from the centre, towards the periphery (-ve → +ve)
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EEG theta waves
Non-REM stage 1 (N1) Theta waves Light sleep | Transition to this stage be associated with hypnic jerks
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N2 sleep stage on EEG
Non-REM stage 2 (N2) Sleep spindles + K-complexes Deeper sleep Represents around 50% of total sleep
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delta waves on EEG
Non-REM stage 3 (N3) Delta waves Deep sleep | Parasomnias such as night terrors, nocturnal enuresis, sleepwalking
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REM sleep on EEG
REM Beta-waves Dreaming occurs | Loss of muscle tone, erections
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stages of sleep with EEG findings
N1 → N2 → N3 → REM Theta → Sleep spindles/K-complexes → Delta → Beta The Sleep Doctor's Brain
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what is interferon alpha
produced by leucocytes antiviral action useful in hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer, hairy cell leukaemia adverse effects include flu-like symptoms and depression
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what is interferon beta
produced by fibroblasts antiviral action reduces the frequency of exacerbations in patients with relapsing-remitting MS
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what is interferon gamma
predominately natural killer cells. Also by T helper cells weaker antiviral action, more of a role in immunomodulation particularly macrophage activation may be useful in chronic granulomatous disease and osteopetrosis
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interferon binding sites
FN-alpha and IFN-beta bind to type 1 receptors whilst IFN-gamma binds only to type 2 receptors.
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what is cerebral perfusion pressure
net pressure gradient causing blood flow to the brain. The CPP is tightly autoregulated to maximise cerebral perfusion. A sharp rise in CPP may result in a rising ICP, a fall in CPP may result in cerebral ischaemia. It may be calculated by the following equation: CPP= Mean arterial pressure - Intra cranial pressure Following trauma, the CPP has to be carefully controlled and the may require invasive monitoring of the ICP and MAP.
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standard deviation
square root variance
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achondroplasia genetics
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. In most cases (approximately 70%) it occurs as a sporadic mutation. The main risk factor is advancing parental age at the time of conception. Once present it is typically inherited in an autosomal dominant fashion.
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achndroplasia features
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
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what is williams syndrome
inherited neurodevelopmental disorder caused by a microdeletion on chromosome 7
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features williams syndrome
``` elfin-like facies characteristic like affect - very friendly and social learning difficulties short stature transient neonatal hypercalcaemia supravalvular aortic stenosis ```
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diagnosis of williams syndrome
Diagnosis is made by FISH studies
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posterior to right kidney
Quadratus lumborum, diaphragm, psoas major, transversus abdominis
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posterior to left kidney
Quadratus lumborum, diaphragm, psoas major, transversus abdominis
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anterior to right kidney
Hepatic flexure of colon
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anterior to left kidney
Stomach, Pancreatic tail
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superior to right kidney
Liver, adrenal gland
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superior to left kidney
Spleen, adrenal gland
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structure of renal hilum
The renal vein lies most anteriorly, then renal artery (it is an end artery) and the ureter lies most posterior.
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contents 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 ```
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histopathology 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
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phases of anaphase
anaphase A: cohesins that bind sister chromatids together are cleaved, followed by shortening of the kinetochore microtubules which pulls the daughter chromosomes to opposite ends of the cell anaphase B: polar microtubules push against each other, causing the cell to elongate
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what does troponin C bind to
calcium ions
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what does troponin T bind to
tropomyosin
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what does troponin I bind to
actin to hold toponin-tropomyosin complex in place
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what is myosin
the thick component of muscle fibres. Actin slides along myosin to generate muscle contraction.
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3 places that control respiration
central regulatory centres central and peripheral chemoreceptors pulmonary receptors
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central regulatory centres
``` medullary respiratory centre apneustic centre (lower pons) pneumotaxic centre (upper pons) ```
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central and peripheral chemoreceptors
central: raised [H+] in ECF stimulates respiration peripheral: carotid + aortic bodies, respond to raised pCO2 & [H+], lesser extent low pO2
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pulmonary receptors
stretch receptors, lung distension causes slowing of respiratory rate (Hering-Bruer reflex) irritant receptor, leading to bronchoconstriction juxtacapillary receptors, stimulated by stretching of the microvasculature
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most common renal stone
alcium oxalate Hypercalciuria is a major risk factor (various causes) Hyperoxaluria may also increase risk Hypocitraturia increases risk because citrate forms complexes with calcium making it more soluble Stones are radio-opaque (though less than calcium phosphate stones) Hyperuricosuria may cause uric acid stones to which calcium oxalate binds 85%
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cystine stones
Inherited recessive disorder of transmembrane cystine transport leading to decreased absorption of cystine from intestine and renal tubule Multiple stones may form Relatively radiodense because they contain sulphur 1%
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uric acid stones
Uric acid is a product of purine metabolism May precipitate 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 Radiolucent 5-10%
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calcium phosphate stones
May occur in renal tubular acidosis, high urinary pH increases supersaturation of urine with calcium and phosphate Renal tubular acidosis types 1 and 3 increase risk of stone formation (types 2 and 4 do not) Radio-opaque stones (composition similar to bone) 10%
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struvite stones
Stones formed from magnesium, ammonium and phosphate Occur as a result of urease producing bacteria (and are thus associated with chronic infections) Under the alkaline conditions produced, the crystals can precipitate Slightly radio-opaque 2-20%
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prolactin function
Stimulates breast development (both initially and further hyperplasia during pregnancy) Stimulates milk production It decreases GnRH pulsatility at the hypothalamic level and to a lesser extent, blocks the action of LH on the ovary or testis.
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prolactin regulation
Prolactin secretion is under constant inhibition by dopamine ``` Increases secretion thyrotropin releasing hormone pregnancy oestrogen breastfeeding sleep stress drugs e.g. metoclopramide, antipsychotics ``` Decreases secretion dopamine dopaminergic agonists
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riboflavin deficiency
Riboflavin is a cofactor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is important in energy metabolism. Consequences of riboflavin deficiency: angular cheilitis
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iron absorption
upper small intestine especially the duodenum about 10% of dietary iron absorbed Fe2+ (ferrous iron) much better absorbed than Fe3+ (ferric iron) absorption is regulated according to body's need increased by vitamin C, gastric acid decreased by proton pump inhibitors, tetracycline, gastric achlorhydria, tannin (found in tea)
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iron distribution
``` total body iron = 4g haemoglobin = 70% ferritin and haemosiderin = 25% myoglobin = 4% plasma iron = 0.1% ```
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what is fabry disease?
Overview X-linked recessive deficiency of alpha-galactosidase A ``` Features burning pain/paraesthesia in childhood angiokeratomas lens opacities proteinuria early cardiovascular disease ```
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primary hyperparathyroidism
PTH (Elevated) Ca2+ (Elevated) Phosphate (Low) Urine calcium : creatinine clearance ratio > 0.01 May be asymptomatic if mild Recurrent abdominal pain (pancreatitis, renal colic) Changes to emotional or cognitive state Most cases due to solitary adenoma (80%), multifocal disease occurs in 10-15% and parathyroid carcinoma in 1% or less
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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
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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 ```
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indications for surgery in primary hyperparathyroidism
Elevated serum Calcium > 1mg/dL above normal Hypercalciuria > 400mg/day Creatinine clearance < 30% compared with normal Episode of life threatening hypercalcaemia Nephrolithiasis Age < 50 years Neuromuscular symptoms Reduction in bone mineral density of the femoral neck, lumbar spine, or distal radius of more than 2.5 standard deviations below peak bone mass (T score lower than -2.5)
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indications for surgery in secondary hyperparathyroidism
Bone pain Persistent pruritus Soft tissue calcifications
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treatment for tertiary hyperparathyroidism
The presence of an autonomously functioning parathyroid gland may require surgery. If the culprit gland can be identified then it should be excised. Otherwise total parathyroidectomy and re-implantation of part of the gland may be required.
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growth hormone source
Anterior pituitary: Somatotrophs comprise 50% of the cells of the anterior pituitary gland
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growth hormone function
Postnatal growth and development Numerous actions on protein, carbohydrate and fat metabolism (including increasing lipolysis and gluconeogenesis) Mechanism of action 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
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growth hormone regulation
``` Increases secretion growth hormone releasing hormone (GHRH): released in pulses by the hypothalamus fasting exercise sleep (particularly delta sleep) ``` Decreases secretion glucose somatostatin (itself increased by somatomedins, circulating insulin-like growth factors, IGF-1 and IGF-2) Conditions associated with GH disorders excess GH: acromegaly GH deficiency: resulting in short stature
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antibody regions
Fab region: antigen-binding fragment - the region that binds to antigens Fc region: fragment crystallizable region - the tail region of an antibody that interacts with cell surface receptors
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leukotriene function
mediators of inflammation and allergic reactions cause bronchoconstriction, mucous production increase vascular permeability, attract leukocytes leukotriene D4 has been identified as the SRS-A (slow reacting substance of anaphylaxis)
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leukotriene production
secreted by leukocytes formed from arachidonic acid by action of lipoxygenase it is thought that the NSAID induced bronchospasm in asthmatics is secondary to the express production of leukotrienes due to the inhibition of prostaglandin synthetase
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renin effects
secreted by juxtaglomerular cells and hydrolyses angiotensinogen to produce angiotensin I
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stimulating renin release
``` hypotension causing reduced renal perfusion hyponatraemia sympathetic nerve stimulation catecholamines erect posture ```
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factors reducing renin secretion
drugs: beta-blockers, NSAIDs
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what is lesch Nyhan syndrome?
known as juvenile gout, is characterized by hyperuricemia. It is a genetic condition with an X-linked pattern of inheritance. It is caused by a defect in the purine salvage pathway due to the absence of the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme which catalyzes the conversion of hypoxanthine to inosine monophosphate (IMP) and guanine to guanosine monophosphate (GMP). The consequence is an accumulation of uric acid. The typical findings supporting this diagnosis in this patient is the aggressive behavior, self-mutilation, intellectual impairment as well as laboratory finding of hyperuricemia.
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what is nyacin?
Niacin is a water soluble vitamin of the B complex group. It is a precursor to NAD+ and NADP+ and hence plays an essential metabolic role in cells. Biosynthesis Hartnup's disease: hereditary disorder which reduces absorption of tryptophan carcinoid syndrome: increased tryptophan metabolism to serotonin Consequences of niacin deficiency: pellagra: dermatitis, diarrhoea, dementia
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what is prader-willi syndrome?
rader-Willi syndrome is an example of genetic imprinting where the phenotype depends on whether the deletion occurs on a gene inherited from the mother or father: Prader-Willi syndrome if gene deleted from father Angelman syndrome if gene deleted from mother 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 ``` Features hypotonia during infancy dysmorphic features short stature hypogonadism and infertility learning difficulties childhood obesity behavioural problems in adolescence ```
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prader willi v angelman
Deletion of chromosome 15 Prader-Willi - paternal Angelman syndrome - maternal
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phases of cardiac action potential
0 Rapid depolarisation Rapid sodium influx These channels automatically deactivate after a few ms 1 Early repolarisation Efflux of potassium 2 Plateau Slow influx of calcium 3 Final repolarisation Efflux of potassium 4 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
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pre-test probability
The proportion of people with the target disorder in the population at risk at a specific time (point prevalence) or time interval (period prevalence)
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post-test probability
The proportion of patients with that particular test result who have the target disorder
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pre-test odds
The odds that the patient has the target disorder before the test is carried out Pre-test odds = pre-test probability / (1 - pre-test probability)
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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)
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organisation of adrenal cortex
``` zona glomerulosa (on outside): mineralocorticoids, mainly aldosterone zona fasciculata (middle): glucocorticoids, mainly cortisol zona reticularis (on inside): androgens, mainly dehydroepiandrosterone (DHEA) ```
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renin
an enzyme that is released by the renal juxtaglomerular cells in response to reduced renal perfusion other factors that stimulate renin secretion include hyponatraemia, sympathetic nerve stimulation hydrolyses angiotensinogen to form angiotensin I
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angiotensin 2
angiotensin-converting enzyme (ACE) in the lungs converts angiotensin I → angiotensin II angiotensin II has a wide variety of actions: 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. Remember that FF = GFR / renal plasma flow stimulates thirst (via the hypothalamus) stimulates aldosterone and ADH release increases proximal tubule Na+/H+ activity
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aldosterone
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
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phas 1 trial
Determines pharmacokinetics and pharmacodynamics and side-effects prior to larger studies Conducted on healthy volunteers
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phase 2 trials
Assess efficacy + dosage Involves small number of patients affected by particular disease May be subdivided into IIa - assesses optimal dosing IIb - assesses efficacy
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phase 3 trials
Assess effectiveness Typically involves 100-1000's of people, often as part of a randomised controlled trial, comparing new treatment with established treatments
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phase 4 trials
Postmarketing surveillance Monitors for long-term effectiveness and side-effects