cardioresp Flashcards
what is a vegetation and which heart condition is it found in
bacterial infection surrounded by a layer of fibrin and platelets found in infective endocarditis
which bacterial infection is the most common cause of infective endocarditis
streptococci
how do you diagnose infective endocarditis
Duke’s criteria
- SYMPTOMS: fever, malaise, sweating, unexplained weight loss
- BLOOD TEST: anaemia, raised inflammatory markers
- BLOOD CULTURE: micro-organism found
- EXAMINATION: new heart murmur
- ECHOCARDIOGRAM: shows vegetation, abscess, valve perforation, dihescnce of valve prosthesis, regurgitation of the affected valve - transoesophageal echo is more sensitive than transthoracic
what are the features of cardiac decompensation in infective endocarditis
frequent coughing
swelling of abdomen and legs
shortness of breath
fatigue
raised JVP (jugular venous pressure)
lung crackles
oedema
name the vascular, embolic and immunological phenomena of infective endocarditis
vascular/embolic:
- stroke
- janeway lesions (irregular non tender hemorrhagic macules on hands and feet)
- splinter/conjunctival haemorrhages
immunological:
- osler’s nodes (painful red lesions of hands and feet)
- Roths spots (white centred retinal hemorrhagic)
what part of the heart does infective endocarditis affect
endocardium
- mostly the valves as the bacteria rush towards sight of damage and the most turbulent blood flow is around the valves
- mostly the aortic valve
aortic>mitral>right sided valves
what increases risk of infective endocarditis
IV drug user: more likely for bacteria to get into the blood, which is the first step
Routine surgeries eg dental surgery - also more likely for bacteria to get into blood
Immunosuppression
Cardiac myopathies: more likely to have damage - bacteria more likely to stick to damaged endocardium
what is dilated cardiomyopathy
dilated and thin walled cardiac chambers with reduced contractility
what does echo show for dilated cardiomyopathy
dilated left ventricle with reduced systolic function (ie reduced ejection fraction) and global hypokinesia
commonest causes of dilated cardiomyopathy
alcoholism
thyroid disease
drugs
familial
autoimmunity
management of dilated cardiomyopathy
- fluid with Na+ restriction
- heart failure meds: ACE inhibitors, beta blockers, diuretics
- anticoagulants
- cardiac devices
- transplant
what is the gold standard treatment for early stage lung cancer
lung resection
what is the first line treatment for metastatic non small cell lung cancer with no mutation and PDL1 > 50% (ie PDL1 positive)
immunotherapy - Anti PD-1 and Anti PD-L1
eg pembrolizumab
what is the first line treatment for metastatic non small lung cancer with no mutation and PDL1 < 50% (ie PDL1 negative)
chemotherapy + immunotherapy
frequent side effects of chemotherapy
fatigue, nausea, bone marrow suppression, nephrotoxicity
first line treatment for metastatic non small cell lung cancer with targetable mutation
oncogene directed treatment (against EGFR, ALK, ROS1) –> tyrosine kinase inhibitor
eg
crizotinib
erlotinib
side effects of oncogene directed lung cancer treatment
rash, diarrhoea, pneumonitis
what is the efficacy of oncogene directed treatment for lung cancer in contrast to standard chemotherapy
improvement in progression free survival but not necessarily overall survival vs standard chemotherapy
treatment for locally advanced lung cancer involving thoracic lymph nodes
surgery + chemotherapy
or
chemotherapy + radiotherapy + immunotherapy
what is the efficacy of immunotherapy treatment for lung cancer in contrast to standard chemotherapy
improvement in progression free survival and overall survival vs standard chemotherapy
what is the role of PDL1 on lung tumour cells
binds to PD1 on T cells, this renders the T cell inactive and stops it killing the tumour cell
-allows tumour cell to survive and proliferate
what is the radical radiotherapy for lung cancer called
SABR
stereotactic ablative body radiotherapy
signs of advanced lung cancer
bone pain
neurological symptoms eg seizures, focal weakness, spinal cord compression
paraneoplastic symptoms eg hypercalcaemia, hyponatramia, clubbing, cushings
cachexia
horners syndrome
pembertons sign (SVC obstruction)
definitive imaging used for staging lung cancer
PET - CT
list the 3 types of biopsies used for lung cancer
bronchoscopy
EBUS/TBNA (endobronchial ultrasound, transbronchial needle aspiration)
CT guided lung biopsies
which biopsy method is used for central airway tumours
bronchoscopy
which biopsy method is used for peripheral lung tumours
CT guided lung biopsy
which biopsy method is used for mediastinum/mediastinal lymph nodes in lung cancer
EBUS/TBNA
which biopsy method is used for staging and tissue diagnosis in lung cancer
EBUS/TBNA
which lung cancer oncogene is linked especially with smokers
BRAF (downstream cell cycle signalling mediator
which lung cancer oncogene is sometimes seen in adenocarcinomas
epidermal growth factor receptor (EGFR) tyrosine kinase
describe the pathogensis of lung cancer and how inhaled carcinogens interact with the lungs
inhaled carcinogens interact with the airway epithelium to form DNA adducts (DNA bound to cancer causing chemicals)
if these DNA adducts persist they lead to the formation of mutations which can cause lung cancer especially if they occur in tumour suppressor genes or oncogenes
what are the levels 0 to 5 of the WHO performance status for lung cancer
0 - asymptomatic
1 - symptomatic but completely ambulatory
2 - symptomatic, in bed <50% of daytime
3 - symptomatic, in bed >50% of day, not bed bound
4 - bed bound
5 - death
which cells do squamous cell carcinomas of lung cancer originate from
bronchial epithelium
which cells do adenocarcinomas of lung cancer originate from
mucus producing glandular tissue
3 cardinal features of asthma
atopy/allergic sensitisation
reversible airway obstruction
airway inflammation - eosinophilic or type 2
what does reversible airflow obstruction in asthma manifest as
expiratory wheeze
which 2 chromosomes have been found to be associated with asthma
IL33
GSDMB
describe type 2 inflammation in asthma
APCs present antigens to naive CD4 T cells causing them to become Th2 cells
this causes formation of
IL13 –> production of mucus and narrowing of airways
IL5 –> eosinophil production
IL4 –> IgE production
what is that test for allergen sensitisation (in asthma)
blood tests for specific IgE antibodies against allergens of interest
what are the 3 tests for eosinophilia and their cut offs for asthma
1) blood test –> above/equal to 300 cells/mcl
2) sputum sample –> above/equal to 3%
3) exhaled nitric oxide –> above/equal to 35 ppb in children, above/equal to 40 ppb in adults
what are the asthma cut offs for spirometry
FEV1/FVC less than/equal to 0.7 in adults, less than/equal to 0.8 in children
what is the test for reversible airway obstruction and what is the asthma cut off
bronchodilator reversibility
greater/equal to 12 %
what are the 3 aims of asthma management and list drugs used for each aim
1) reduce airway inflammation
- leukotriene receptor antagonist
- inhaled corticosteroids
2) acute symptomatic relief (smooth muscle relaxation)
- anticholinergics
- beta 2 agonists
3) steroid sparing therapies for severe asthma
- biologics against IgE –> anti IgE antibodies
- biologics against eosinophil –> anti IL5 antibody, anti IL5 receptor antibody
what is mepolizumab
biologic for severe eosinophilic asthma
anti IL5 antibody
IL5 regulates recruitment, activation, production of eosinophils
mepolizumab prescribing criteria
over/equal to 6 years of age
blood eosinophils over/equal to 300 cells/mcl in the last 12 months
over 4 exacerbations requiring oral steroids in past 12 months
how do corticosteroids reduce eosinophilic inflammation
reduce recruitment of eosinophils from blood to airways
induce apoptosis of eosinophils if they enter airways
what is omalizumab
anti IgE monoclonal antibody
binds to and captures IgE, preventing it from interacting with mast cells and basophils
prescription criteria for omalizumab
severe and persistent allergic (IgE mediated) asthma
over/equal to 6 years of age
4 or more courses of oral corticosteroids in the past year
total serum IgE count is 30 - 1500 IU/ml
describe the pathogenesis of an acute lung attack in a school child
reduced IFN alpha, beta, gamma
- reduced antiviral response, increased viral proliferation –> prolonged illness
eosinophilic inflammation –> responsive to corticosteroids
reduced peak expiratory flow rate
- increased airway obstruction causing acute wheeze –> responsive to bronchodilators
describe the amount of ventilation across the lung
top of lung:
pleural pressure is more negative
greater transmural pressure gradient
larger and less compliant alveoli
less ventilation
bottom of lung:
pleural pressure is less negative
smaller transmural pressure gradient
smaller and more compliant alveoli
more ventilation
describe the amount of perfusion across the lung
top of lung:
lower intravascular pressure
less recruitment
greater resistance to flow
lower flow rate
bottom of lung:
greater intravascular pressure (gravity effect)
more recruitment
less resistance to flow
higher flow rate
what is the pressure of oxygen in the alveoli
13.5 kPa (101 mmHg)
what is the oxygen pressure in the blood before and after oxygen transport at the alveoli
before - 5.3 kPa (40mmHg)
after - 13.5 kPa (101 mmHg)
what is the oxygen saturation of the blood before and after oxygen transport at the alveoli
before - 75%
after - 100%
what is normal value for gas exchange time and for pulmonary transit time
gas exchange time - 0.25 s
pulmonary transit time - 0.75 s
what is compliance and how do you calculate it
the tendency of a material to distort under pressure
change in volume / change in pressure
what is elastance and how do you calculate it
the tendency of a material to recoil to its original volume
change in pressure / change in volume
give causes of acute respiratory failure
pulmonary - aspiration, infection, primary graft dysfunction
extra pulmonary - trauma, pancreatitis, sepsis
neuromuscular - mysasthenia gravis, GBS (guillain barre syndrome)
give causes of chronic respiratory failure
pulmonary - COPD, CF, lung fibrosis, lobectomy
musculoskeletal - muscular dystrophy
give causes of acute on chronic respiratory failure
infective exacerbation of CF, COPD
myasthenia crisis
post operative
what is normal minute ventilation value and how is it calculated
tidal volume x breathing rate = 0.5 L x 12 breaths/min= 6 L/min
what is normal alveolar ventilation and how is it calculated
(tidal volume - dead space) x breathing rate = 0.35 x 12 = 4.2 L/min
what are respiratory failures 1 - 4
1) hypoxamic (oxygen <60)
increased shunt fraction (fraction of cardiac output that is deoxygenated)
2) hypercapnic (co2 >45)
decreased alveolar minute ventilation
3) perioperative resp failure
hyperaemic or hypercapnic
4) shock associated
list the pulmonary and extra pulmonary causes/triggers of ARDS
pulmonary
- infection
- aspiration
- burns (inhalation)
- surgery
- drug toxicity
- trauma
extra pulmonary
- infection
- pancreatitis
- trauma
- surgery
- drug toxicity
- burns
- transfusion
- bone marrow transplant
list the in vivo evidence for ARDS
leucocyte activation and migration
release of DAMPs: HMGB-1 and RAGE
release of cytokines: IL6, IL8, IL 1B, TNF gamma
TNF signalling
cell death
which therapies have been trailed for ARDS
salbutamol
statins
steroids
surfactant
neutrophil esterase
N acetyl cysteine
GM- CSF
which therapies are currently being trialed for ARDS
microvesicles
mesenchymal stem cells
keratinocyte growth factor
ECCO2R
high dose vitamin C, thiamine, steroids
list 4 drugs used to treat ARDS
pyridostigmine
plasma exchange
IViG
Rituximab
list the order of respiratory support from mild ARDS to severe progressed ARDS
conservative fluid management
low volume ventilation
Increasing PEEP (positive end expiratory pressure)
prone positioning
neuromuscular blockade
inhaled pulmonary vasodilators
extracorporeal membrane oxygenation (ECMO)
what are the two pressure points that the lungs should be kept between
lower inflection point: minimal pressure needed to keep airways open/needed for optimal alveolar recruitment
upper inflection point: above this point, will need to apply disproportionally more pressure to achieve same increase in gas exchange/alveolar recruitment
what is gas trapping in ventilation
for some people on ventilation it takes a longer time for them to expire
so they may not be able to expire all the air out of their lungs
so with each breath, more air gets stuck in the lungs, increasing the pressure inside
this impacts on alveolar recruitment and lung perfusion
2 key requirements for using ECMO
reversible disease process
and
unlikely to lead to prolonged disability
describe the events in the inflammatory response of ARDS
apoptosis/necrotic of type 1 alveolar cells
denunded basement membrane
resident macrophages release IL6, IL8, TNF alpha
activation of alveolar neutrophils - release PAF (platelet actuating factor), leukotrienes, oxidants, proteases
damaged endothelial cells of capillaries and holes in epithelium of capillaries
neutrophils leak out of capillaries into inetrstitium (space between capillaries and alveoli)
results in oedema and secondary inflammation
get a widened oedematous interstitium
describe the symptoms of an upper respiratory tract infection
cough
sneezing
runny/stuffy nose
headache
sore throat
describe the symptoms of a lower resp tract infection
fever
fatigue
muscle aches
productive cough
wheezing
breathlessness
pneumonia symptoms
chest pain
high fever
cyanosis - blue tinting of lips
severe fatigue
what is a DALY
disability adjusted life years
= YLL (years of life lost) + YLD (years lost to disability)
common causative agents of bacterial respiratory infections
streptococcus pneumoniae
myxoplasma pneumoniae
haemophilus influenzae
mycobacterium tuberculosis
common causative agents of viral respiratory infections
influenza A / B
human rhinovirus
human metapneumovirus
respiratory syncytial virus
coronavirus
is streptococcus pneumoniae gram positive or negative
gram positive
list 3 properties of streptococcus pneumonia as a pathogen
gram positive
extracellular
opportunistic pathogen
causative agents of community acquired pneumonia
streptococcus pneumoniae
myxoplasma pneumoniae
chlamydia pneumoniae
haemophilus influenzae
staphylococcus aureus
causative agents of hospital acquired pneumonia
E coli
psuedomonas aeruginosa
Klebsiella species
Enterobacter spp
acinetobacter spp
staphylococcus aureus
causative agents of ventilator associated pneumonia
psuedomonas aeruginosa
staphylococcus aureus
enterobacter
how does pneumonia lead to ARDS
pneumonia –> lung injury –> arterial hypoxaemia –> ARDS
how does pneumonia lead to sepsis
lung injury, bacteraemia, systemic inflammation –> organ dysfunction and injury –> sepsis
what is the scoring method used for bacterial pneumonia
CURB 65
confusion
urea > 7 mmHg
resp rate >= 30 breaths/min
bp systolic <90 mmHg, diastolic <= 60 mmHg
age >= 65 years
medication for severe and non severe Hospital acquired pneumonia
not severe = doxycycline
severe = tazocin + gentamicin
(for 5-7 days)
medication for Community acquired pneumonia with a CURB65 score of 0
amoxicillin
medication for Community acquired pneumonia with a CURB65 score of 1 -2
amoxicillin + clarithromycin
medication for Community acquired pneumonia with a CURB65 score of 3 - 5
benzylpenicillin + clarithromycin
supportive therapy for bacterial pneumonia
oxygen
fluids
analgesia
nebulised saline (helps with expectoration)
chest physiotherapy
what do penicillin antibiotics target
proteins in bacterial cell wall
this prevents transpeptidation
what do macrolide antibiotics target
bacterial ribosomes
this prevents protein synthesis
what is an opportunistic pathogen
takes advantage of changes in conditions to become pathogenic (eg immunosuppression)
what is a pathobiont
normally commensal but becomes pathogenic when it enters the wrong environment eg a different anatomical site
describe the pathophysiology of viral infections and how they cause disease
viral infections cause
- local immune memory
- mediator release
- cellular inflammation
- damage to epithelium
–> loss of chemoreceptors
–> loss of cilia
–> bacterial growth
–> poor barrier to antigens
3 factors which cause severe disease
highly pathogenic strains
no prior immunity
predisposing conditions/diseases eg diabetes, pregnancy, copd, asthma,
what does H1N1 influenza A target and in which part of resp tract
hameogluttinin of H1N1 targets alpha 2,6 sialic acid in upper airway
what does H5N1 avian flu target and in which part of resp tract
haeogluttinnin of H5N1 targets alpha 2,3 sialic acid in lower airway
what does SARS CoV 2 target and in which part of resp tract
spike protein of SARS CoV2 targets ACE 2 in nasal epithelium and pneumocyets
describe the features of the respiratory epithelium that prevent infection spread
tight junctions - prevent systemic infection
antimicrobials - recognise and degrade pathogens and their products
interferon pathways - stimulated by viral infection - up regulate antiviral proteins and apoptosis
mucosal/ciliary epithelium - prevents attachment and clears airways
pathogen recognition receptors -recognise pathogens inside and outside of cell
which part of resp tract is IgA found
nasal cavity
- many IgA receptors
- IgA homodimer is stable in this protease rich environment
which part of resp tract is IgG found
alveoli
- thin alveolar walls allow passing of plasma IgG into alveolar space
why are smokers more susceptible to SARS CoV 2 infection
they have more ACE 2 –> this is targeted by the spike protein on the virus
why is the vaccination for influenza poor
vaccine induced immunity quickly disappears/decreases
immunity is homotypic
need yearly vaccine
why is there no vaccine for RSV
poor immunogenicity
which has a longer incubation period, RSV or influenza
RSV
RSV symptoms in infants
croupy cough
hypoxameia and cyanosis
chest wall retractions
tachypnoea and apneic episodes
expiratory wheeze
prolonged expiration
rales and rhonchi
nasal flaring
risk factors for RSV in infants
premature birth
congenital heart and lung disease
anti inflammatories for SARS CoV 2
dexamethasone
tocilizumab (anti IL6R)
sarilumab (anti IL6)
anti virals for SARS CoV2
remdesivir - blocks RNA-dependant RNA polymerase activity
paxlovid - antiviral protease inhibitor
casirivimab + imdevimab - monoclonal neutralising antibodies
interplay between viral infections and chronic lung disease
viral bronchiolitis causes asthma
rhinovirus causes copd and asthma exacerbations
viral infections cause secondary bacterial pneumonia
interplay between viral infections and bacterial infections
pattern of cerebrospinal meningitis after pneumonia/influenza
what are the advantages and disadvantages of the cardiopulmonary exercise test
advantages
- continuous monitoring for safety
- quantifies result in relation to metabolism
- precise and reproducible result
disadvantages
- needs skilled supervision
- expensive
- needs dedicated space
what is measured in a cardiopulmonary exercise test and what is the primary output
ECG
ventilation
O2
Co2
whilst on cycle ergometer or treadmill with incremental inverse in intensity
(primary output is peak VO2)
what type of test is the 6 minute walk test
sub maximal
what type of test is the 6 minute walk test
sub maximal
what is measured in the six minute walk test
how far can walk in six minutes - distance
heart rate
pulse oximetry
perceived exertion
advantages and disadvantages of 6 minute walk test
+
cheap
participant controlled pace
applicable to many clinical populations
- need long unobstructed course
doesn’t take pace into account
what is measured in incremental shuttle walk test and what is primary outcome
total distance walked - 10m circuit, beeps 1 minute apart, with each beep the laps you have to do increases, until you voluntarily stop
heart rate
pulse oximetry
perceived exertion
primary outcome = distance walked
advantages and disadvantages of incremental shuttle walk test
+
cheap
participant controlled pace
applicable to many clinical populations
- need long unobstructed course
incremental nature may be difficult for some
ceiling effect at 1020 m
participants with poor pace management may be penalised
which two cells mostly make up the interstitium of the lungs
fibroblasts
macrophages
contrast type 1 and 2 alveolar cells/pneumocytes
1: flatter shape, squamous cell, involved in gas exchange
2: cuboidal shape, have microvilli, secrete surfactant, divide into type 1 and 2 cells
contrast prognosis of UIP and DIP/NSIP patterns of ILD
UIP - much worse prognosis over time than DIP/NSIP
what test is done for checking the diffusing capacity of the lungs
DLCO is reduced - test measuring lungs diffusing capacity for carbon monoxide
histopathology pattern seen in IPF (idiopathic pulmonary fibrosis)
UIP (usual interstitial pneumonia) pattern: spacial and temporal heterogeneity with microscopic honeycomb cysts and fibroblastic foci
what is seen on IPF CT scan
traction bronchiectasis
sub pleural honeycombing
basal predominance
which medication makes IPF worse
corticosteroids –> they are immunosuppressants so increase risk of death
effect of anti fibrotic on IPF
slow down progression but do not cure
IPF treatment
O2 therapy and anti fibrotic
but only definitive treatment is lung transplant
predisposing factors for IPF
genetic - MUC5B, DSP
environmental triggers - smoke, dust, pollutants, viruses
cellular ageing - telomere attrition, senescence
proposed mechanism for IPF
damage to epithelium - type 1 pneumocytes release TGF beta 1
causes type 2 pneumoncytes to stimulate fibroblasts to become myofibroblasts
myofibroblasts produce collagen and elastic fibres then apoptose
get too much proliferation of type 2 pneumocytes, resulting in too many myofibroblasts which also don’t apoptosis properly
get lots of collagen and interstitial thickens
this remodelling and scar tissue affects gas exchanged ventilation (lung becomes thick)
proposed mechanism for IPF
damage to epithelium - type 1 pneumocytes release TGF beta 1
causes type 2 pneumoncytes to stimulate fibroblasts to become myofibroblasts
myofibroblasts produce collagen and elastic fibres then apoptose
get too much proliferation of type 2 pneumocytes, resulting in too many myofibroblasts which also don’t apoptosis properly
get lots of collagen and interstitial thickens
this remodelling and scar tissue affects gas exchanged ventilation (lung becomes thick)
Is hypersensitivity pneumonitis reversible if the cause is removed
yes, if not left for so long that chronic inflammation and irreversible changes occur
symptoms/cause of acute vs chronic hypersensitivity pneumonitis
acute: SOB, fever, chest tightness, headache –> due to intermittent and high level exposure
chronic: sustained SOB, due to long term low level exposure
what is heard on auscultation in hypersensitivity pneumonitis
inspiratory squeaks
what is seen on BAL for hypersensitivity pneumonitis
lymphocytes > 30%
what patterns are seen on CT for hypersensitivity pneumonitis
centrilobular ground glass nodules
ground glass
air trapping
mosaic attenuation pattern
three density patterns
investigations for hypersensitivity pneumonitis
lung biopsy - granulomas and lymphocytes
auscultation - inspiratory squeaks
check for specific IgG
BAL
HRCT
pulmonary function tests
treatment for hypersensitivity pneumonitis
immunosuppression
corticosteroids
anti fibrotic
remove the cause
mechanism of hypersensitivity pneumonitis
inhaled antigen in alveolus is picked up by macrophage and taken to lymph node
presented on MHC 2 to naive T cells causing maturation
T cell stimulates B cells to produce IgG
TYPE 3 HYPERSENSITIVITY: IgG with antigen forms immune complexes which settle in capillary wall and trigger inflammation and necrosis
(complement cascade –> neutrophil degranulation –> vessel inflammation and necrosis)
and
TYPE 4 HYPERSENSITIVITY: T cells and macrophages surround antigen, forming granulomas
2 types of systemic sclerosis and effects on lungs
limited cutaneous SSc - pulmonary hypertension
diffuse cutaneous SSc - ILD
skin manifestations of SSc
digital ulcers
sclerodatyly
abnormal nail bed on capillaroscopy
telangiectasia
reynauds
treatments for SSc ILD
immunosuppressants
anti fibrotics
which treatment to avoid for SSc
corticosteroids - high dose causes renal failure
which treatment to avoid for SSc
corticosteroids - high dose causes renal failure
HRCT pattern for SSc ILD
NSIP (non specific interstitial pneumonia) pattern
what does microvascular heterogeneity mean
the vascular endothelial structure is different depending on the tissue function - organotypic expression profiles
how do you calculate (estimate) rate of diffusion
(surface area x concentration gradient) / membrane thickness
roles of nitric oxide as an anti inflammatory
reduces
VSMC proliferation
platelet activation
LDL activation
release of super-oxide radicals
monocyte adhesion
induces
vasodilation
list some triggers for endothelial activation
smoking
mechanical stress
oxidised LDL deposition
High glucose
list the 3 layers of artery walls
tunica adventitia
tunica media
tunica intima
which vessels have pericytes in their walls and name a role of them
capillaries
they’re also called pericapillary cells
can help construct the vessel
what are VEGF-A and FSF-1, what are they secreted by and what is their role
angiocrine factors
secreted by the capillary endothelium
maintain tissue homeostasis and repair
3 most common sites for atherosclerosis and why
carotid bifurcation
coronary artery
aortic bifurcation
what are the 2 intracellular oxidative enzymes that macrophages use to further oxidise oxLDLs they have engulfed, and turn into foam cells
NAPDH oxidase
myeloperoxidase
what are the 3 roles of IL1 in atherosclerosis
positive feedback to Nuclear Kappa Factor beta (up-regulates it)
triggers intracellular cholesterol crystals
up regulates VCAM1 expression –> increases monocyte migration through endothelium into proteoglycan matrix
role of PDGF (platelet derived growth factor) in atherosclerosis
stimulates SMC proliferation
role of TGF B (transforming growth factor beta) in atherosclerosis
changes SMCs from contractile into synthetic - synthetic SMCs produce collagen - this ECM they lay down will form the fibrous capsule for the atherosclerotic plaque
what are PCSK9 inhibitors used for and how do they work
used for severe / statin resistant hyperlipidaemia
PCSK9 degrades the LDL receptor (LDLR)
the LDLR removes cholesterol from the blood and stops cholesterol biosynthesis
is MCP1 a cytokine or chemokine
chemokine
which receptor does MCP1 bind to
a monocyte G protein coupled receptor CCR2
what are the proteins on the surface of lipoproteins called
apoproteins
surgical interventions for atherosclerosis
percutaneous coronary intervention
carotid endarterectomy
percutaneous transluminal balloon angioplasty
bypass surgery
investigations for familial hypercholestrolaemia
lipid profile
genetic testing
how does familial hypercholestrolaemia accelerate the process of atherosclerosis
mutation means the the LDLR on hepatocytes is absent
so hepatocytes can’t take up LDL
so LDL levels in plasma increase
so more LDL is taken up by macrophages
this accelerates the process of atherosclerosis
how does coves infection cause procoagluation
infection –> cytokine storm –> endothelial activation –> procoagulant switch
effect on thromboinflammation on the lungs
causes ARDS
- microthrombi form in the lungs
- increased capillary permeability in lungs
- causes pulmonary oedema
- reduced gas exchange
- type 1 resp failure
how is tumour vasculature different from normal vasculature
vessels are irregularly shaped, dilated, more leaky and haemorrhagic
describe the process of sprouting angiogenesis
1) selection of sprouting endothelial cells
- changes in polarity
- modulation of EC-EC contacts
- ECM degradation
2) start of sprouting
- new ECM is deposited
- EC proliferation
- invasive behaviour
3) lumen formation
- proliferation of stalk cell
4) maturation and perfusion
- stabilisation of EC-EC adhesions and PC contacts
- full blood flow through the lumen
- reduction in EC proliferation
- increase in quiescent signals
describe the process of sprouting angiogenesis
1) selection of sprouting endothelial cells
- changes in polarity
- modulation of EC-EC contacts
- ECM degradation
2) start of sprouting
- new ECM is deposited
- EC proliferation
- invasive behaviour
3) lumen formation
- proliferation of stalk cell
4) maturation and perfusion
- stabilisation of EC-EC adhesions and PC contacts
- full blood flow through the lumen
- reduction in EC proliferation
- increase in quiescent signals
