CSIM2- mechanisms and investigations of disease Flashcards Preview

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Flashcards in CSIM2- mechanisms and investigations of disease Deck (184):
1

2 types of imaging that use NON-ionising radiation

US
MRI

2

3 pros of US

no radiation
patient centred
can be focussed

3

3 cons of US

hard to interpret
needs specialist operator
may give false reassurance

4

4 cons of MRI

slow
needs IV contrast to be effective (anaphalaxis, NSF)
needs a specific question
accessibility

5

contraindications for MRI

any metal:
pacemaker
insulin pumps
hearing aids
metal clips

6

4 uses of interventional radiology

biopsies
drainage
angioplasty
tumour ablation

7

two groups particularly at risk from radiation

pregnant
children

however clinical need outweighs risk

8

1 CT scan is equal to what life time risk of cancer

1/1000

9

what are 2 potential risks of using IV contrast?

anaphylaxis
contrast nephropathy (tell the radiologist about any renal impairment)

10

what are the RED FLAGS in sepsis according to the sepsis trust?

Pulse > 130
resp. >25
lactate >2
purpuric rash
less than A on AVPU

11

define secondary brain injury

damage due to hypoxic insult some time after the initial injury

12

how to calculate the cerebral perfusion pressure?

CPP = MAP - ICP

(mean arterial pressure - intracranial pressure)

13

when ICP increases how does the body compensate?

squeeze out some of the CSF and venous blood

14

what happens in the skull when the brain can no longer compensate for an increase in pressure?

uncal herniation (transtentorial herniation)
blood vessels kink

15

4 signs of increased ICP

decreased level of consciousness
pressor response
projectile vomiting
CN 6 palsy

16

what is another name for the pressor response and what are the characteristic triad?

cushing's response:
irregular breathing
increased BP
reduction in HR

17

4 signs of brainstem herniation

CN 3 palsy
motor posturing
lower extremity rigidity
hyperventilation

18

what is the normal range of ICP? when to treat?

5-15mmHg , treat above 20

19

how can the ICP be lowered artificially?

remove mass/ lesion
drain CSF
reduce parenchymal volume
reduce cerebral blood flow

20

how can we reduce the parenchymal vol. in raised ICP?

osmotic therapy
sometimes resection

21

how can the arterial blood flow to the brain be reduced in raised ICP?

sedation
mechanical ventilation
avoid fever
treat seizures

22

how can cerebral blood in the veins be reduced in raised ICP?

head up
avoid jugular pressure

23

how does sedation and controlled ventilation reduce ICP?

if o2 decreases then there will be vasodilation in the brain -> increased blood flow
same with high co2

24

what is the main imaging tool in major trauma and why?

CT because it shows where the bleeding is coming from

25

5 reasons for a trauma call and an example for each?

physiological- ABC approach
anatomical- 2 or more proximal long bone fractures/ head penetration etc.
high risk mechanism of injury- car crash
multiple trauma victims
discretionary-consider age, co-morbidities

26

what is the bodies response to reduced MAP due to haemorrhage? (3)

baroreceptor response : increase SNS and decrease PNS
endocrine response : catecholamine and steroid release
reduced renal perfusion ->RAA axis activation -> Na and hence water retention

27

where does blood go in major trauma?

blood on the floor and 4 more:
1. long bones
2. pelvis
3. abdomine
4. thorax

28

what would you expect an ABG to look like in major trauma?

pH: decreased
pCO2: decreased
pO2: variable
lactate: increased
bicarb: decreased
base excess: decreased

i.e. metabolic (lactic) acidosis with resp. compensation where possible

29

what is likely to happen to Hb immediately after major trauma?

stay the same: it is a conc. so blood loss will not reduce the conc. of Hb immediately. in the following hours fluid will be sucked in from surrounding tissue (or given IV) so the Hb will DECREASE

30

how should the circulating blood volume be restored?

give blood ideally , or FFP (fresh frozen plasma)/ platelet
dont give crystalloids/ colloids much anymore due to hypotermia

31

explain the trauma TRIAD OF DEATH

patient becomes acidotic due to vasocontriction, hypotension (and hypoperfusion) causing anaerobic respiration.
this leads to decreased heart performance
this leads to hypothermia (also due to cold fluid admin. and exposure)
hypothermia causes decreased coagulation
this has the effect of exacerbating the acidosis

32

what is an immunoassay?

biochemical test that measures the conc. or presence of proteins (or other macro molecules) with antibodies

33

advantages of monoclonal immunoassay?

recognizes single epitote (foreign target antigen)
little batch variability
high specificity

34

pros and cons of immunoassay

pros:
automated therefore fast
sensitive
widely applicable e.g. BNP

cons:
cross-reactive: hard to produce an antibody that only reacts to the epitote you want
some are manual
heterophilic antibodies screw results

35

clinical application for immunoassay?

cancer diagnosis and prognosis

36

microarrays advantages

can look at 1000s of antigens at the same time so cost effective

37

microarray diadvantages

imprecise
not yet robust enough for clinical practice

38

define proteomics

study of the full set of proteins encoded by the human genome (30,000 genes)

39

which lab tests are used in proteomics

2D electrophoresis (protein material in disease sample is compared to non-diseased sample
mass spec (produces peptide finger print)
microarrays

40

which lab tests are used in metabolomics?

mass spec
NMR

41

what are the limiting factors in the -omics?

huge amount of data with complex interpretation
statistical significance not proven yet

42

define genomic test

test nucleic acid to answer a diagnostic / prognostic question

43

diagnostic genetic testing is what? and what are the practical problems

finding the gene mutation to confirm the diagnosis (usually 100% sensitive)

multiple genes cause same phenotype
different phenotypes
unknown genes

44

what is it that causes degenerative disorders of the CNS?

aggregates of misfolded proteins

where these deposit determines what kind of problem you get

45

on post-mortem what are you able to see in Alzheimers?

senile plaques: short amino acid called amyloid Beta. this comes from a much bigger pre-cursor protein

Tau protein (particularly in FTLD): these cause nerve cells to die off

46

how can we slow the accumulation of amyloid beta in alzheimers

inhibit the enzyme that is breaking down the large protein precursor into amyloid beta

47

why do tau proteins aggregate in dementia?

enzymes cause phosphorylation of tau which reduces micro tubule biding and promotes aggregation (because they're hydrophobic)

48

what is seen on microscopy in PD?

lewy bodies
neural loss

49

what could be a diagnostic biomarker in PD?

alpha-synclein

50

how could vaccination work as a therapy in degenerative disorders?

infusion of antibodies into patients could reduce symptoms

51

how do lysosomal storage disorders lead to symptoms?

loss of function of an enzyme leads to progressive accumulation of metabolite within lysosomes leads to organ disfunction

52

in which cells is the pathology in Gaucher's disease?

accumulation of metabolites in macrophages -> skeletal problems and anaemia. also spleen and liver problems

53

treatment for Gaucher's disease?

replace defective enzymes (B-glucosidase)

54

what is hunter syndrome?

enzyme deficiency that causes skeletal deformities, developmental delay and recession, cardiac and lung abnormalities and hepatosplenomagaly

55

how do pharmacological chaperones treat lysosomal storage defects?

stabilizes proteins in the endoplasmic reticulum to prevent protein misfolding

56

define iron deficiency anaemia and symptoms

57

effects of iron overlaod

liver cirrhosis
diabetes
cardiomyopathy
endocrine dysfunction

58

how does iron enter a cell?

transferrin

59

what is haemachromotosis?

elevated transferrin iron saturation and elevated ferritin leads to complications of high iron (cariomyopathy, diabetes, cirrhosis, arthritis) and hypogonadotrop ic hypogonadism

60

treatment for haemachromotsis?

regular phlebotomy and reduced iron diet

61

acute and chronic effects of copper overload?

acute : GI spasm, kidnet damage, rhabdomyolysis, haematemesis

Chronic : cirrhosis, diabetes, renal damage, neurophsychiatric problems

62

Wilsons disease is a problem of...

copper retention: due to failure of the copper to get into the bile it isnt excreted

63

symptoms/ signs of Wilsons

cirrhosis, extra-pyramidal symptoms, cardiomyopathy and nephocalcinosis

64

name a copper deficiency disorder

Menke's disease
severe developmental delay and hair/ skin/ nail defects

65

sensitivity = ...

true positives / (true positives + false negatives)
i.e. who has the disease

66

specificity = ...

true negs / (true negs + false positives)
i.e. who hasnt got the diease

67

define positive predictive value and give equation

% of people who actually have the disease out of those who tested positive
positive predictive value = true pos. / (true pos. + false pos.)

68

define likelihood ratio

likelihood of the result meaning there is disease vs. there being no disease

69

equation for positive likelihood ratio

LR+ = sensitivity / (1- specificity)

70

equation for negative likelihood ratio

LR- = ( 1 - sensitivity) / specificity

71

roughly what LR+ is considered useful ?

>10

72

roughly what LR- is considered useful?

the lower the better , 1 is USELESS

73

describe endocrine signalling

uses hormones which are secreted into the blood so they can be carried to their site of action. they are present at very low levels.
act via receptors on or in target cells
the same hormone can have a heterogeneous response depending on the cell

74

what is paracrine signalling?

the chemical acts on the adjacent cell

75

what is autocrine signalling? e.g.?

target site is on the same cell - amplification process
T-cell lymphocytes

76

what is juxtacrine signalling?

contact-dependent signalling
i.e. grow when not touching, stop on contact (cancer doesnt have this)

77

define ligand

extra-cellular signalling molecule

78

what is a third messenger system and what is another name for it?

molecule that transmit messages from outside the nucleus to inside or visa verse
also called DNA binding molecules

79

why do most signal transduction therapies target the beginning of a pathway?

the higher up the pathway the more specific and the less unpredictable outcomes

80

define second messenger

small molecules synthesised in cells in response to an external signal which are responsible for intracellular signal transduction e.g. Ca2+

81

4 ways specificity of biosignalling can be influenced

1. different interactions between ligand and receptor
2. cell- specific expression of receptors (only some cells will express the correct receptor)
3. cell- specific expression of signal transduction proteins (so the same signal - receptor combination can have different effects in the cell)
4. cell-specific expression of effector proteins - there can be a varied response depending on what the cell does in response to the signal

82

how does a direct ligand-gated channel work?

a signal, acting as a ligand, binds to a receptor changing its shape such that a specific ions can now flow through

83

around 40% of medical drugs use what kind of signal transduction?

G-protein coupled type

84

which type of signal transduction is used in most of our senses? (smell, sight, taste)

GPCR

85

explain how a mutation in the V2R gene on the X chromosome results in congenital diabetes insipidus in males

normally AVP (anti-diuretic hormone) binds to the V2 vasopressin receptor (GPCR) and stimulates water reabsorption. if the V2R gene is inactivated then this cannot happen so cannot generate appropriately concentrated urine

86

what area are tyrosine kinase-linked signals important

cell growth, differentiation and survival

87

how could the inhibition of EGFR have therapeutic effects in cancer patients?

EGFR is expressed to varying degrees in a variety of cancers e.g. colorectal, pancreatic, head and neck, renal, breast. by introducing an anti-body to bind to extracellular domain of EGFR , growth factor can be blocked

88

what are the 4 types of receptor in signal transduction?

1. direct ligand gated channel
2. G protein coupled receptor
3. tyrosine kinase- linked
4. intracellular steroid / thyroid type

89

where are intracellular receptor proteins found?

in the cytosol or nucleus

90

what type of molecules can reach intracellular receptors?

small or hydrophobic

91

two examples of hormones that work on intracellular receptors?

thyroid
steriod

92

how do intracellular signals have an effect on the body?

act as transcription factors, turning on specific genes

93

what are the 5 components of the innate immune system?

1. physical / chemical barriers
2. phagocytic leukocytes
3. dendritic cells
4. natural killer T cells
5. plasma proteins (complement)

94

2 components of adaptive immunity

1. humoral (B cells which mature into antibody secreting plasma cells)
2. cell mediated (T cells that mature into effector helper T and cytotoxic T cells)

95

how are specific antibodies made?

randomly through recombination of regions of the immunoglobulin genes.
B cells that make antibodies against foreign molecules AND self are allowed to be made.
there is then a process of negative selection where the B cells making self antibodies are DESTROYED

96

how can the process of antibody production lead to autoimmune disease

the negative selection process doesnt always destroy the B cells that produce antibodies with a low affinity to self

97

what makes autoimmunity pathogenic?

it is normal for there to be autoantibodies in individuals. it is pathogenic when:
1. there is activation of T/B cells and amplification of autoantibody responses
2. there is increased or novel exposure of 'self' antigen

98

4 functions of antibodies

1. opsonisation -> phagocytosis
2. cytotoxicity
3. immune complex formation
4. mediate inflammation

99

pathophys of Goodpastures syndrome

AKA anti-GBM disease
anti-GBM antibodies bind to the basement membrane of capillaries causing the WBC to attack it.
leads to inflammation of the vessels -> glomerulonephritis and alveolar capillartitis

100

anti-body mediated AID is what type of hyper-sensitivity?

type II

101

how do streptococcal cell wall antigens cause acute rheumatic fever?

they cross react with cardiac heart muscle

102

what antigens are present in Goodpastures syndrome?

collagen type IV basement membrane

103

type III hypersensitivity is mediated by what?

immune complexes:
ineffective clearance of immune complexes by the innate immune cells leads to an inflammatory response

104

what are the two general ways the immune system can be over active?

failure to switch off
wrong target

105

allergy is what kind of hypersensitivity?

type I

106

describe sensitisation in a type I hypersensitivity reaction

antigen comes into contact with a B cell
it is presented to a T helper cell
IgE is produced for that antigen
a mast cell is coated in this IgE

107

what is it that causes the inflammatory response in type I hypersensitivity?

degranulation of the mast cell on re-rexposure

108

what dose of adrenaline do you give in anaphylaxis? 3 other things?

0.5ml of 1 in 1000 IM
fluid bolus
chlorphenamine 10mg IV
hydrocortisone 200mg IV (for the late phase)

109

when would you do a mast cell tryptase test and why?

1hr after onset of anaphylaxis
to monitor progress

110

3 medications to give on discharger following anaphylaxis?

oral prednisolone
antihistamine (10/ 20mg PRN)
CONSIDER adrenaline autoinjector x2

111

4 tests available for allergy follow up?

RAST testing for specific IgE
skin prick
oral challenges
intradermal testing

112

what is Bayes theorem ?

the pre-test characteristics of a patient must be considered along with the test result to work out the post test probability of having a disease

113

if the likelihood ratio of a test is 10, what is the approx. change in probability with a positive result?

add on 45%

114

if the likelihood ratio of a test is 2, what is the approx. change in probability with a positive result?

add on 15%

115

with what pre-test probability might you not want to do the test and why?

very low- would you treat even if positive?
very high- just treat anyway

116

why is there increased lactate in sepsis?

1. macrophage activity
2. decreased clearance of lactate
3. increased anaerobic respiration

117

what is adult respiratory distress syndrome? what does it look like on CXR?

injury to the basement membrane of the alveoli causes them to fill with fluid
diffuse opacity

118

when and why would you do a tryptase test?

24 hrs after anaphylaxis to rule out mastocytosis (excess mast cells)

119

what is von willebrand factor and where is it stored?

blood glycoprotein involved in haemostasis
stored in the endothelial cells

120

how does von williebrand factor work?

released into plasma when endothemilum is damaged
traps passing platelets

121

how does the endothelium regulate vWf to prevent clots?

releases nitrous oxide to prevent adhesion (can i bind here please? NO!)

122

how is vasculitis classified?

small, medium and large

123

what is the most common vasculitis?

GCA

124

how is vision lost in GCA?

occultion of the blood supply to the eye

125

how is GCA diagnosed? and treated?

biopsy
steroids

126

what is Bechet's disease?

small vessel inflammation in veins and arteries that causes mouth ulcers, genital sores, eye inflammation , rashes

127

what changes are associated with endothelial dysfunction?

reduced NO bioavailability
pro-vaso-constriction
pro-coagulopathy
pro-inflammation
pro-oxidative stress

128

what type of vascular disease is anti-neutrophil cytoplasic antibdies (ANCA) associated with?

small vessel vasculitis

129

what are the systemic symptoms of small vessel vasculitis?

ENT- saddle bridge nose
lungs- wheeze, breathlessness, dry cough, haemoptysis
skin- ulcers, rash, necrosis
eys- dry, red gritty, painful eyes with or w/o vision loss
nerves- loss of sensation
bowels- bleedins, diarrhoea, abdo. pain

130

how are macrophages primed?

NK cells and T cells release IFN-gamma when a barier has been penetrated
this upregulates the expression of MHCII

131

how do marophages kill bacteria?

recognise PAMP: increase reactive o2 molecules and lysosome number

132

other than phagcytosis, what do macrophages do when primed?

release cytokine that have the following affect:
1. active compliment cascade
2. active vascular endothelium
3. increase anti-bodie production
4. recruits other cells

133

where are NK cells made?

bone marrow

134

what can NK cells do?

kill tumour and virally infected cells

135

how do macrophages and NK cells have an amplification effect?

macrophages activate NK cells and NK cells release IFN-gamma which activates macrophages

136

where are neutrophils made and what attracts them?

bone marrow
TNF-a

137

what is the 'bridge' between innate and adaptive immune systems?

dendritic cells:
awaits sampling by t cells at lymph nodes

138

what is meant by 'contexualised' discrimination? (immune system)

our bodies will allow the retention of harmless 'non-self' e.g. in the gut

139

how is peripheral tolerance achieved?

Tregs made in the peripheries and tolerogenic DCs can turn off self reactive T-lyphocytes by cell- cell inhibition

140

what are t-regs and what ar the types?

CD4+ T lymphocytes which suppress potentially deleterious activities of T lymhocytes
thymic tregs (central tolerance)
peripheral tregs- induced in peripheries `

141

AIRE deficency is an example of what mechanism of auto-immunity?

failure of central tolerance: non-expression of self antigen -> organ specific auto-immunity and chronic mucocutaneous candidiasis

142

give an example of a disorder of Treg cells?

IPEX syndrome

143

define primary immundeficincy

loss OR GAIN in function

144

what type of infection are neutrophils, compliment and antibodies responible for clearing?

EXTRAcellular

145

Tx for anti-body, compliment , neutrophil deficiency?

abx prophylaxis
anti fungal prophylaxis (particularly in compliment)
replacement Ig

146

what could be a non-congenital cause of neutrophil deficiency

chemo/ radio therapy
bone marrow failure

147

how are t cells involved in extra cellular infection clearing?

B cell actvation

148

how do t cell deficient patients present/

persistent viral infection (t cells clear intracelluar infections)
protazoal infections +/- bacterial infections

149

tx for t lymphocyte deficiency ?

abx prophylaxis
anti fungal prophylaxis (particularly in compliment)
replacement Ig
haematopoietic stem cell transplant

150

how can phagocyte deficiency lead to non-infectious resp. failure?

cells arent cleared so get a build up surfactant

151

3 types of rejection, their time periods and what mediates it?

hyper-acute: straight away- anti-bodies (pre-existing)
acute: days/ weeks - T-cells and anti-bodies
chronic: months/ years - compliment, ab, adhesion molecules

152

what does chronic rejection cause?

FIBROSIS
atherosclerosis
inflammation/ scarring

153

what are the three criteria for graft v host disease?

graft has immunologically competent cells
host appears foreign to the graft, i.e. it has alloantigens that stimulate the graft
host is unable to mount an effective immune response to the graft

154

3 ways to prevent rejection?

ABO matching (prevents hyper acute)
HLA matching e.g. with family members
immunosuppression: destroy T cells with serotherapy, prednisolone

155

what is graft v host disease?

when bone marrow/ stem cells rejects host
RARE: liver transplant (there are lots of immune cells here)

156

who is at risk of GVHD?

neonates
immunocompetent

157

which organs does acute GVHD effect?

skin (painful rash, blisters)
liver (raised LFTs and possibly jaundice)
gut (anorexia, dyspepsia, bleeding, diarrhoea)

158

what factors increase risk of GVHD?

sex mismatch
previous pregnancies
peripheral cells worse than core cells
age

159

what investigation is used to determine extent of liver fibrosis?

biopsy is the gold standard

160

what can LFTs tell you about fibrosis?

AST/ALT ratio

161

why do blockages form in the liver in cirrhosis?

regeneration leads to nodule formation

162

which cells cause pulmonary fibrosis?

abnormal activation of fibroblasts

163

what will the U&Es look like in chronic renal failure?

high phosphate (kidneys cant clear it)
low calcium

164

two main causes of high calcium

malignancy (boney mets or ectopic parathyroid tissue)
hyperparathyroidism

165

define carcinogenesis

process of a normal cell becoming a cancer cell

166

what is the smallest detectable tumour?

1cm

167

why do cells not normally metastasize to other parts of the body? e.g. why no liver cells on skin?

cellular proteins and surface glycoproteins have a contact inhibition system

168

define hypertrophy

increase in size of tissue due to increase in size of cells

169

define hyperplasia

increase in size of tissue due to increase in number of cells

170

define metaplasia

replacement of one fully differentiated tissue with another due to persistant injury. when this stimulus is removed it will return to initial state

171

define dysplasia

archetectual and cytological changes similar to malignancy.
some features of cancer but not cancer yet- can also return to normal if stimulus removed

172

3 steps in chemical carcinogenesis

1. initiation- chemical damage to DNA and repair had failed before replication
2. Promotion- reversible process that requires multiple exposure. if a promotor is removed the cancer could stabilise
2. Progression- irreversible process that involves multiple complex DNA changes

173

2 types of non-ionising radiation that could cause cancer?

radio-waves
UV

174

which tissue is particularly sensitive to ionising radiation?

breast, thyroid, bone marrow

175

why are male pilots more likely to have daughters than sons?

exposure to radiation
y chromosome is more susceptible to it

176

which UV type has the most effect on DNA and which is the most clinically relevant?

UVC is the most potent but us mostly absorbed by the air so is negligible.
UVB is the most important in cancer

177

how does non-ionising radiation cause changes in DNA?
and how do cells normally stop this?

electron excitation
nucleotide excision repair pathway

178

what % of cancers are thought to be due to infection globally?

15%

179

what does EBV increase risk of?

Hodgkins and burkett's lymphoma

180

example of exogenous hormones causing cancer

HRT, COCP*- over exposure to oestrogen linked with breast cancer

only if this is used after oestrogen would normally be lowered

181

whats the difference between somatic and germline mutation

germline- error in every bit of DNA. can be hereditary but not always
somatic- in the tumour there is a mutation but this is not present in the other cells (unless present in the germline cells). this cannot be passed on

somatic mutations and germline mutations can affect the same genes

182

how can mutations occur in normal cell division?

mis-segregation
mitotic recombination

183

how many cancers are familial?

10%

184

why is it dificult to get chemo to cancer cells?

they are very hypoxic so arent well supplied by our blood vessels. only about 20% of cells can be reached