cardio and respiratory Flashcards
(513 cards)
1
Q
when do we hear S1 heart sound
A
closure of mitral and tricuspid valve
2
Q
when do we hear S2 heart sound
A
closure of aortic and pulmonary valve
3
Q
when do we hear S3 heart sound
A
congestive cardiac failure
due to rapid filling and expansion of ventricles
early diastole
4
Q
when do we hear S4 heart sound
A
systemic hypertension, hypertrophic cardiomyopathy, ischemia
atrial hypertrophy/ stiff ventricles
late diastole
due to forcegul atrial contractions
5
Q
what are some congenital structural heart diseases
A
atrial septal defect
ventricular septal defect
coarctation fo aorta
patent foramen ovale
tetralogy of fallot
patent ductus arteriosus
6
Q
what are types of valvular defects (4)
A
aortic stenosis
aortic regurgitation
mitral stenosis
mitral regurgitation
7
Q
what is aortic stenosis preceded by
A
aortic sclerosis
8
Q
risk factors of atrial stenosis
A
hypertension
LDL
smoking
elevated C reactive protein
CKD
radiotherapy
age
9
Q
causes of aortic stenosis
A
rheumatic heart disease
congenital heart disease
calcium build up
10
Q
pathophysiology of aortic stenosis
A
degeneration or congenital malformed valves or anti Streptococcal Av wrongly attack valves leading to inflammation of valve endocardium -> cause fibrosis and calcification of aortic valve –> LV need contract harder to pump blood –> concentric LV myocardial hypertrophy –> hypertrophic LV becomes stiff overtime and harder to fill –> decrease Cardiac output –> diastolic dysfunction –> pressure overload in LV back to LA –> cause LA dilate and lead to increase pressure ij lungs –> pulmonary congestion
11
Q
symptoms and signs of aortic stenosis
A
ejection systolic murmur
syncope on exertion
angina on exertion
diffuse crackles on auscultation of lungs and dyspnoea
12
Q
how to diagnose aortic stenosis
A
doppler echo (to detect blood flow and pressure gradient)
13
Q
management of aortic stenosis
A
transcatheter valve replacement
surgical valve prosthesis
14
Q
what is aortic regurgitation
A
diastolic leakage of blood from aorta to LV
due to incompetence of valve leaflets resulting from intrinsic valve disease or dilation of aortic root
15
Q
is aortic regurgitation chronic or acute
A
can be both
16
Q
what happens in acute aortic regurgitation
A
sudden onset of pulmonary oedema and hypotension or cardiogenic shock
17
Q
what happens in chronic aortic regurgitation
A
culminate into congestive cardiac failure
18
Q
causes of chronic aortic regurgitation
A
rheumatic heart disease
infective endocarditis
aortic valve stenosis
congenital heart defects
congenital bicuspid valves
19
Q
causes of chronic aortic regurgitation
A
Marfan’s syndrome
connective tissue disease
collagen vascular diseases
20
Q
pathophysiology of aortic regurgitation
A
aortic root dilation / inflammation of valvular endothelium lead to abnormal valve leaflet –> valve leaflet close poorly when aortic pressure is higher than LV during diastole –> back flow of blood from aorta to LV –> acute dilation cause increase stroke vol / chronic LV dilates and eccentrically hypertrophies –> excessive stretching weakens myocardium and unable to contract properly –> systolic heart failure
21
Q
aortic regurgitation symptoms and signs
A
diastolic murmur
S3 gallop in early diastole, due to rapid filling and expansion of ventricles
angina on exertion
fatigue
increase back pressure in lungs causing pulmonary congestion
22
Q
presentation of acute aortic regurgitation
A
cardiogenic shock
tachy
cyanosis
pulmonary oedema
diastolic murmur
23
Q
presentation of chronic aortic regurgitation
A
wide pulse pressure
24
Q
how to diagnose aortic regurgitation
A
echocardiography
25
management for aortic regurgitation (for acute and chronic respectively)
acute : aortic valve replacement
chronic: vasodilator therapy
26
what is mitral stenosis
obstruction to LV inflow at mitral valve due to structural abnormality of mitral valve
may lead to pulmonary hypertension and right HF
27
causes of mitral stenosis
rheumatic fever
carcinoid syndrome
SLE
mitral anular calcification
amyloidosis
congenital deformity of valve
28
pathophysiology of mitral stenosis
recurrent inflammation --> fibrous decomposition and calcification of mitral valve leaflets ad chordae tendineae --> thicken and shorten of chordae tendineae --> fusion of leaflets, very narrow -> decrease in orifice area -> obstructed blood flow thru MV --> impaired emptying of LA -> impaired filling of LV --> decrease SV and CO --> congestive HF --> increase in RV pressure --> hypertrophy of RV --> right side HF
29
symptoms and signs of mitral stenosis
mid diastolic murmur
afibrillation
right side HF/ cardiogenic shock/ congestive HF
LA enlargement
30
presentations of mitral stenosis
dyspnoea
murmur
dysphagia
opening snap
haemoptysis
31
how to diagnose mitral stenosis
ECG
chest x ray
transthoracic echocardiography
32
management of mitral stenosis
if progressive asymptomatic -> no therapy
severe asymptomatic -> adjuvant balloon valvotomy
severe symptomatic -> diuretic, balloon valvotomy, valve replacement and repair adjunct B-blockers
33
what is mitral regurgitation
caused by disruption in any part of mitral valve apparatus
abnormal reversal of blood flow from LV to LA
34
causes of acute mitral regurgitation
mitral valve prolapse
rheumatic heart disease
infective endocarditis
post valvular surgery
prosthetic mitral valve dysfunction
35
causes of chronic mitral regurgitation
rheumatic heart disease
SLE
scleroderma
hypertrophic cardiomyopathy
drug related
36
pathophysiology of mitral regurgitation
back flow of blood from LV to LA due to impaired closure of valve --> increase vol and pressure in LA --> increase vol push bk into LV in next diastole --> LV dilation due to remodelling --> decrease in LV systolic function --> back pressure in LA and lung vasculature leading to congestion / decrease SV and cardiac output --> congestive HF
37
symptoms of mitral regurgitation
holosystolic murmur
S3 heart sound
decrease in oxygen saturation, wheeze, crackles, tachypnoea
sign of congestive HF
38
how to diagnose mitral regurgitation (6)
ecg
CXR
transthoracic echocardiography
cardiac mri
ct scan
39
management of acute mitral regurgitation
repair or replace supporting valve structures
prosthetic ring to reshape the valve
40
management of chronic mitral regurgitation
asymptomatic -> monitor or surgery
symptomatic --> first surgery plus medical treatment
41
what is cardiomyopathy
makes heart muscle harder to pump blood to rest of body
42
which types of HF are result of cardiomyopathies (3)
1. dilated
2. hypertrophic
3. restrictive
43
what is dilated cardiomyopathy
most common cause of HF
progressive irreversible
cause systolic dysfunction with HF
44
what is hypertrophic cardiomyopathy
genetic CVD
sudden cardiac death in preadolescent and adolescent children
increase in LV wall thickness not solely explained by abnormal loading conditions
45
what is restrictive cardiomyopathy
idiopathic/familial/associated with systemic disorders
restrictive ventricular filling pattern
46
what is infective endocarditis
infection of endocardium or vascular endothelium of heart
47
main cause of infective endocarditis
bacteria entering blood stream and form a vegetation in endocardium
48
what is the most common bacteria in endocartitis
Streptococci
49
how to diagnose infective endocarditis
blood test show anaemia and raised markers of infection
blood cultures isolate a microorganism
echocardiogram show vegetation, abscess, valve perforation, dehiscence of prosthetic valve, regurgitation of affected valve
transoesophageal echo has higher sensitivity than transthoracic
50
symptoms of infective endocarditits
fever
malaise
sweats
unexplained weight loss
new heart murmur
51
what symptoms of cardiac decompensation in infective endocarditis
SOB
frequent coughing
swelling of legs and abdomen
fatigue
52
what are clinical signs of infective endocarditis
raised JVP
lung crackles
oedema
53
what part of heart does infective endocarditis affect
endocardium
valves of heart
most common aortic valve
54
what is vegetation in infective endocarditis
changes to valve thickness or failure in their ability to opena nd close
55
how IV drugs users are more dangerous to infective endocarditis
due to repeated injection more at risk to expose bloodstream to bacteria on surface of skin or use of non sterile needles
56
what is difference between rheumatic fever and rheumatic heart disease
fever: temporary inflammatory condition
heart disease: permanent condition as a sequala of previous rheumatic fever causing permanent damage to heart valves
57
which bacteria cause rheumatic fever
group A streptococci
58
is there a long lag between rheumatic fever and rheumatic heart disease
yes
7 years to 30years
59
what are the most common valvular dysfunction caused by rheumatic heart disease
mitral stenosis
60
which valve can be affected by acute rheumatic fever
aortic valve (more common) and tricuspid
causing regurgitation and then stenosis
61
clinical signs of mitral stenosis
fluid overload eg peripheral oedema
malar flush
hoarse voice
loud S2
RV heave
62
symptoms of mitral stenosis
haemoptysis
fatigue
SOB
paroxysmal nocturnal dyspnoea
palpitation
63
why is there hoarse voice in mitral stenosis
compression of left recurrent laryngeal nerve by dilated left atrium
64
what are in increased risk in mitral stenosis
stroke and embolic events
65
major Jones' criteria for rheumatic heart disease
presnece of grp A streptococci infection
carditis
arthritis
chorea
erythema marginatum
subcutaneous nodules
66
minor Jones' criteria for rheumatic heart disease
polyarthralgia
fever
elevated acute phase reacts (CRP/ESR)
prolonged PR interval
67
pathognomic features of rheumatic heart valves
leaflet or chordal thickening
prolapse leaflets
excessive leaflet tip motion during systole
68
management of mitral stenosis
valve commissurotomy (percutaneous or surgical)
valve replacement
management of complications (eg HF and AF) using vit K antagonist
69
pathogenesis of allergic asthma
allergen cause sensitises airway and cause inflammation -> airway remodelling
recruitment of inflammatory cellls into airway
structural change in airway, increase in goblet cells and mucus production
increase amt of matrix and size and amt of smooth muscle cells
narrowed airway
70
what is the name of abnormal air flow in brocnhocostriction
turbulent flow
71
why some ppl who are sensitised develop asthma
hv allergies but not asthma
can be genetically susceptible of allergic asthma
72
what are the steps in Type 2 Immunity allergic asthma
1. exposure to antigen
2. allergen binds to lung dendritic cell MHC ll
3. APC carried by MHC ll to mediastinal lymphocytes
4. Th0 differnetiate into Th1 and Th2
5. Th2 differnetiates to IL-4, IL-5, IL-13
6. eosinophilic airway inflammation
7. mast cell proliferation, IgE synthesis, mucin secretion
73
function of IL-4
convert B plasma cells to secrete IgE
74
function of IL-5
recruit eosinophils into airways and promote their survival causing eosinophilic airway inflammation
75
unction of IL-13
mucus secretion
76
what are some tests for allergic sensitisation
allergy skin tests
blood tests (for IgE antiobodies to allergens of interest)
77
tests for eosinophilia
blood test
sputum
78
what is a non invasive biomarker for type 2 airway inflammation
fraction of exhaled nitric oxide (FeNO)
>40ppb in adults
>35ppb in children
79
management of asthma to reduce airway eosinophilic inflammation (2)
inhaled corticosteroids (ICS)
leukotriene receptor antagonsits
80
management of asthma for acute symptomatic relief
Beta-2 agonists (smooth muscle relaxation)
anticholinergic therapies (smooth muscle relaxation)
81
management fo asthma with steroid sparing therapies
anti IgE antibody
anti-IL-5 antibody
anti-IL-5 receptor antibody
82
what is the mechanism of corticosteroids
reduce eosinophil numbers through apoptosis
reduce mast cell numbers
smooth muscle relaxation
reduce mucus secretion
83
what is LABA in approaches to treat asthma symptoms
B2 agonists to causing smooth muscle relaxation and dilatation of the airways
84
pathogenesis of acute asthma attack
1. exposure to allergens eg pollution, smoke, dust
2. asthma attack
3. if infection predominating, asthma patients have reduced IFV so increase viral replication
4. prolonged illness
5. reduce peak expirating flow rate and increase airway obstruction
6. increase airway eosinophilic inflammation responsive to corticosteroid
85
is eosinophil responsive to corticosteroids
yes
86
what is anti-IgE antibody therapy
humanised anti-IgE monoclonal antibody
binds and captures circulating IgE to prevent interaction with mast cells and basophils to stop allergic cascade
reduce IgE production
87
what is omalizumab
Anti-IgE antibody
but very expensive
88
example of anti-IgE antibody
omalizumab
89
example of anti-IL-5 antibody to treat asthma
mepolizumab
90
what is mepolizumab
anti-IL 5 antibody
91
when do we use mepolizumab
severe eosinophilic asthma
92
what is dupilumab
anti-IL 4Ra subunit therapy
93
what is biggest risk factor of male for respiratory failure
smoking
94
what is biggest risk factor of female for respiratory failure
household air pollution
95
what is pulmonary transit time
the time taken for blood to pass through the pulmonary circulation
96
when will we have alveolar deadspace
well ventilated + poor perfusion
V/Q ration high
97
when will we have intrapulmonary shunt
poorly ventilated + well perfused
low V/Q ratio
98
what is minute ventilation
tidal vol x breathing frequency
99
what is alveolar ventilation
gas entering and leaving alveoli
(tidal vol - dead space) x breathing frequency
100
where is V/Q ratio highest
apex of lung
101
what is meaning of compliance of lung tissue
tendency to distort under pressure (change in ventilation/change in pressure)
102
what is meaning of elastance of lung tissue
tendency to recoil to its orig vol
(change in pressure/change in ventilation)
103
risk factor of chronic RF
COPD
pollution
recurrent pneumonia
CF
pulmonar fibrosis
neuro-muscular disease
104
risk factor of acute RF
infection (bacteria, viral)
aspiration
trauma
pancreatitis
transfusion
105
pathology of acute lung injury
alveolar macrophages activated by inflammation infection
release more cytokines (IL-6 and IL-8 and TNF alpha)
protein rich oedema build up in lung
inactivation of surfactant
alveoli less efficient at expanding
get migration of neutrophils into interstitium
increase distance between capillary and alveoli
further d.d. for gas exchange --> less efficient
106
what is the role of salbutamol in treating RF
relieve symptoms of asthma and chronic obstructive pulmonary disease (COPD) such as coughing, wheezing and feeling breathless.
relaxing the muscles of the airways into the lungs
107
what is ARDS
acute respiratory distress syndromes
life-threatening lung injury that allows fluid to leak into the lungs
108
what are some therapeutic intervention to treat underlying disease of RF
inhaled therapies (bronchodilators, vasodilators)
steroids
antibiotics
anti virals
109
what are some therapeutic intervention for multiple organ support
cardio: fluids, vasopressors, inotropes, vasodilators
renal: haemofiltration, haemodialysis
immune: plasma exchange, convalescent plasma
110
consequence of ARDS
poor gas exchange
infection (sepsis)
inflammation
systemic effects
111
what are different types of ventilation
volume controlled
pressure controlled
assisted breathing modes
advanced ventilatory modes
112
what is the scoring system of RF
murray score
113
what is ECMO
extracorporeal membrane oxygenation
a form of life support for ppl w injuries for heart or lung
114
how does ECMO work
help remove CO2 and input O2
115
pathogenesis of lung cancer
1. interaction between inhaled carcinogens and epithelium of upper and lower airways
2. formation of DNA adducts (cancer causing chemicals)
3. persisting DNA adducts cause mutation and genomic alterations
116
what are differnet types of lung cancer (4)
1. sqaumous cell carcinoma
2. adenocarcinoma (most common)
3. large cell lung cancer
4. small cell lung cancer
117
what are some important oncogenes
1. epidermal growth factor receptor (EGFR) tyrosine kinase
2. anaplastic lymphoma kinase (ALK) tyrosine kinase
3. c-ROS oncogene 1 (ROS) receptor tyrosine kinase
4. BRAD
118
which gene mutation in lung adenocarcinoma
EFGR tyrosine kinase
119
which gene mutation in non small cell lung cancer
ALK tyrosine kinase
c-ROS receptor tyrosine kinase
BRAF
120
symptoms of lung cancer (6)
cough
weight loss
breathlessness
fatigue
chest pain
haemoptysis
121
neurological features of advanced lung cancer
focal weakness
seizures
spinal cord compression
bone pain
paraneoplastic syndromes
122
what is pemberton's sign
SVC obstruction
123
what are some imaging for lung cancer
CXR
staging CT (chest + abdo)
PET-CT
124
what is useful to exclude occult metastases
PET-CT
125
what can be used to stage mediastinum and achieve tissue diagnosis and access peripheral lung tumors
biopsy
126
Staging -- what is T1-4 for (2)
tumor size and location
127
Staging -- what is N0-3 for
lymph node involvement (mediastinum and beyond)
128
Staging -- what is M0-1c for (2)
metastases + number
129
what is the grading of patient fitness according to WHO performance status
0-5 (asymptomatic to death)
130
what are the surgery options for lung cancer (4)
wedge resection
segmental resection
lobectomy
pneumonectomy
131
what is another option than surgery for early stage lung cancer
radical radiotherapy
132
what are the systemic treatments for lung cancer (3)
1. oncogene-directed
2. immunotherapy
3. cytotoxic chemotherapy
133
when is oncogene directed systemic treatment used
first line treatment for metastatic NSCLC with mutation
134
mechanism of immunotherapy for lung cancer
1. orig PD-L1/PD-L binding inhibits T cell killing tumor cell
2. immunotherapy uses anti PD-1 to bind on PD-1 causing PD-1cannot bind to PD-L1 receotor
3. make it available to T cell to kill tumor cell
135
when is immunotherapy used
first line treatment for metastatic NSCLC with no mutation and PDL > 50%
136
when is cytotoxic chemotherapy used
first line treatment for metastatic NSCLC with no mutation and PDL < 50%
can combine with immunotherapy
137
side effects of immunotherapy for lung cacner
immune-related side effects (thyroid, skin, bowel, liver, lung)
138
side effects of cytotoxic chemotherapy for lung cancer
fatigue
nausea
bone marrow suppression
nephrotoxicity
139
what are the treatments for early stage disease in lung cancer
surgery
radiotherapy with curative intent
140
what are the treatments for locally advanced disease in lung cancer
surgery + adjuvant chemotherapy
radiotherapy + chemo +/- immunotherapy
141
what are the treatments for metastatic disease in lung cancer
with targetable mutation: tyrosine kinase inhibitor
142
when to use immunotherapy alone for lung cancer
no mutation
PDL-1 positive
143
when to use standard chemotherapy + immunotherapy for lung cancer
no mutation
PDL-1 negative
144
what abnormalities can we check in ECG (3)
conduction
structural
perfusion
145
what is atrial fibrillation
irregular and abnormally HR
can be fast or slow
146
what can be seen on atrial flutter ECG (2)
regular saw tooth pattern in baseline
atrial to ventricular beats at 2:1 or 3:1 ratio or higher
*saw tooth not always visible in all leads
147
what happens in ECG for 1st degree heart block (2)
1. prolonged PR segment / interval caused by slower AV conuction
2. regular rhythm 1:1 P: QRS
148
cause of 1st degree heart block
slower AV conduction
progressive disease of ageing
149
what happens in ECG for 2nd degree heart block type 1
progressive PR prolongation until missing QRS
150
characteristic of 2nd degree heart block type 1 heart beat
regularly irregular
151
cause of 2nd degree heart block type 1
diseased AV node
152
what is 2nd degree heart block type 2
regular P waves but only some are followed by ARS
no P-R prolongation, PR is normal
153
characteristic of 2nd degree heart block type 2 heart beat
regularly irregular
154
what happens in ECG for 3rd degree heart block
regular P waves and QRS but no relationship between P and R
can hv hidden P waves within bigger vectors
155
management for 3rd degree heartblock
back up pacemaker
156
cause of 3rd degree heartblock
non sinus rhythm
157
diseases with 3rd degree heart block
congenital heart disease, fibrosis, ischaemic heart disease, infections, autoimmune conditions
158
diseases with 2nd degree heart block type 1
drugs, MI, myocarditis
159
diseases with 2nd degree heart block type 2
MI, fibrosis, cardiac surgery, inflammatory conditions, hyperkalaemia
160
management of 1st degree heart block
stopping AV blocking drugs.
161
management of 2nd degree heart block type 1`
stopping AV blocking drugs.
162
management of 2nd degree heart block type 2
cardiac monitoring, temporary pacing, or pacemaker insertion
163
management of 3rd degree heart block
cardiac monitoring, pacing, or permanent pacemaker
164
what happens in ECG for ventricular tachycardia
hidden P waves (dissociated atrial rhythm)
regular and fast rate
165
what is the risk of ventricular tachycardia
deteriorate into fibrillation (cardiac arrest)
166
can we use defibrillators for ventricular tachycardia and why
yes, as it is shockable rhythm
167
what happens in ECG for ventricular fibrillation
fast and irregular heart rate
168
can we use defibrillators for ventricular fibrillation and why
yes, shockable rhyhtm
169
what happens in ECG for ST elevation
ST segment elevated above >2mm isoelectric line
regular rhythm and normal rate
170
causes of ST elevation
infarction (tissue death caused by hypoperfusion)
171
what happens in ECG for ST depression
ST segment depressed above >2mm isoelectric line
regular rhythm and normal rate
172
causes of ST depression
myocardial ischaemia (coronary insufficiency)
173
what is dilated cardiomyopathy (2)
dilated chambers
thin walls with reduced contractility
174
what will be shown on echocardiogram in dilated cardiomyopathy
dilated LV
reduced systolic function (ejection fraction_
hypokinesis
175
which part of heart does dilated cardiomyopathy typically affect
RV and LV
176
common causes of dilated cardiomyopathy
idiopathic
genetic
toxins
pregnancy (peripartum cardiomyopathy)
viral infections (myocarditiis)
tachycardia-related cardiomyopathy
thyroid disease
muscular dystrophies
177
how to treat dilated cardiomyopathy (5)
sodium glucose transporter reuptake inhibitor
diuretics
anticoagulation for AF
cardiac devices
medical HF therapy
178
examples of sodium glucose transporter reuptake inhibitor to treat dilated cardiomyopathy (2)
dapagliflozin
empagliflozin
179
examples of medical heart failure therapy for dilated cardiomyopathy
ACEi
beta blockers
mineralocorticoid receptor antagonsits
180
symptoms of right heart failure
peripheral oedema
eg leg swelling, raised jugular venous pressure
181
symptoms of left heart failure
pulmonary oedema
182
what is hypertrophic cardiomyopathy
genetic disorder
183
which part of heart hypertrophic in hypertrophic cardiomyopathy
LV hypertrophy
184
cause of hypertrophic cardiomyopathy (what kind of mutation)
missense mutation in 1 of at least 10 genes that encode proteins of the cardiac sarcomere
185
symptoms of hypertrophic cardiomyopathy
majority asymptomatic
some present with severe limiting symptoms of dyspnea, angina, syncope, or death
186
hypertrophic cardiomyopathy pathophsyiolgy
1. genetic, storage disease, neuromuscular or mito disorders, malformation syndromes
2. thickening and disarray of LV myocardium (can happen in any region of LV)
3. involve interventricular septum
4. obstruction of flow thru LV outflow tract
5. disorganised myocytes disrupt signal conduction
6. ventricular arrhythmias
7. sudden cardiac death
187
therapy for obstructive hypertrophic cardiomyopathy (4)
beta blockers
surgical therapy
PTSMA
pacing therapy
188
beta blocker example for obstructive hypertrophic cardiomyopathy
diltiazem
disopyramide
cibenzoline
189
medical therapy for non- obstructive hypertrophic cardiomyopathy with LVEF > 50% (2)
Beta blocker
diuretics (low dose)
190
what is obstructive hypertrophic cardiomyopathy
plaque builds up in coronary arteries
cause arteries narrowing
191
medical therapy for non- obstructive hypertrophic cardiomyopathy with LVEF < 50% (4)
Beta blocker
ACEi
Mineralocorticoid receptor antagonist
192
treatment for non- obstructive hypertrophic cardiomyopathy with therapy resistent
cardiac resynchronisation
ventricular assit devices
heart transplant
193
what is restrictive cardiomyopathy
presence of restrictive ventricular filling pattern
194
causes of restrictive cardiomyopathy
idiopathic
familial (troponin I mutations)
haemochromatosis
amyloidosis
sarcoidosis
Fabry's disease
195
medical treatment for restrictive cardiomyopathy (4)
ACEi
angiotensin receptor ll blockers
diuretics
aldosterone inhibitors
196
what are management for immunosuppression for restrictive cardiomyopathy
steroids
197
non medical treatment for restrictive cardiomyopathy
pacemaker
cardiac transplantation
198
roles of vascular endothelial cells (2)
barrier function
leukocyte recruitment
199
roles of platelets (2)
thrombus generation
cytokines and growth factor release
200
monocyte-macrophages role (4)
foam cell formation
cytokine and growth factor release
major source of free radicals
metalloproteinases
201
roles of vascular smooth muscle cells (3)
migration and proliferation
collagen synthesis
remodelling and fibrous cap formation
202
role of T lymphocytes (4)
macrophage activation -- CD4 Th1
macrophage de-activation CD4 Treg
VSMC death -- CD8 CTL
B cell / Ab help -- CD4 Th2
203
what is the main inflammatory cell in atherosclerosis
macrophages derived from monocytes
204
roles of inflammatory macrophage
adapted to kill microorganism
205
function of non inflammatory and resident macrophages
spleen -- iron homeostasis
alveolar resident macrophages -- surfactant lipid homeostasis
homeostatic functions at parenchymal
206
what are oxidised LDLs / modified LDLs
chemical and physical modifications of LDL by free radicals, enzymes, aggregation
families of highly inflammatory and toxic forms of LDL in vessel walls
207
steps for modification of subendothelial trapped LDL
1. LDLs leak thru endothelial barrier due to endothelial activation in areas of vortex
2. LDL trapped by binding to sticky matrix carbohydrates in sub-endothelial layer and becomes susceptible to modification
3. free radical attacj from activated macrophages (oxidation)
4. LDL oxidatively modified by free radicals
5. oxidified LDL phagocytosed by macrophages and stimulates chronic inflammation
macrophages now known as foam cells
208
what is Familial hyperlipidemia (FH)
autosomal genetic disease
failure to clear LDL from blood
elevated cholesterol
209
which enzyme inhibitorknown for lowering plasma
HMG-CoA reductase inhibitors
210
which gene degrades the number of LDLreceptors
PCSK9
211
what are ABCA and ABCG
cholesterol export pumps
export selective to apolipoprotein A
removes cholesterol from arteries and return to liver
212
what are macrophage scavenger receptor
on macrophages to function in endocytosis and degradation of modified (acetylated) LDLs
213
what is CD204
macrophage scavenger receptor A
214
what does macrophage scavenger receptor A do (3)
binds to oxidised LDL
binds to gram +ve bacteria eg Staphlococci and streptococci
binds tp dead cell
215
what does macrophage scavenger receptor B do (3)
binds to oxidised LDL
binds to malaria parasites
binds to dead cell
216
what is CD36
macrophage scavenger receptor B
217
what kind of oxidative enzymes do macrophages have to modify native LDL (3)
NADPH Oxidase
Myeloperoxidase
generation of H2O2
218
why do we need to generate free radicals to further oxidise lipoproteins
bleach further an damage inside of artery to cause plaque to fall apart
219
how are foam cells formed
macrophages accumulate modified LDLs to become foam cells
220
how are monocytes recruit in athersclerosis
plaque macrophages express inflammatory factors
221
what inflammatory factors are there (2)
cytokines
chemokines
222
what are cytokines roles in athersclerosis
protein immune hormones that activate endothelial cell adhesion molecules
223
what are chemokines role in athersclerosis
small proteins chemoattractant to monocytes
224
what is IL-1
cytokines
225
role of IL-1
triggers intracellular cholesterol crystals and NFkB
coordinate multiple process eg cell death, cell proliferation and elevated CRP
226
is athersclerosis higher or lower in humans with anti-IL-1 antibodies
lower
227
what are monocyte chemotactic protein -1 (MCP-1)
chemokine
228
role of MCP-1
bind to monocyte G-protein coupled receptor CCR2
229
is athersclerosis higher or lower in MCP-1 deficient or CCR2 deficient mice
lower
230
what do macrophages in plaques do (4)
1. generate free radicals that further oxidise lipoproteins
2. Phagocyte modified lipoproteins and become foam cells
3a. express cytokine mediates to recruit monocytes
3b. express chemo-attractant and growth factors for VSMC
3c. Express proteinases to degrade tissue
4. macrophage apoptosis
231
in athersclerosis when macrophages release growth factors what is the result
recruit VSMC
stimulate them to migrate, survive, proliferate, deposit extracellular matrix
232
role of platelet derived growth factor (3)
VSMC chemotaxis
VSMC survival
VSMC division (mitosis)
233
role of transforming growth factor Beta
increase collage synthesis
matrix deposition
these make fibrous cap thicker so cells becomes less contractile to maintain BP
234
role of metalloproteinases (MMPs)
activate each other by proteolysis
degrade collage and tissue
235
what are the effects of plaque erosion or rupture
blood coagulation at site of rupture may lead to an occlusive thrombus and cause cessation of blood flow
236
steps of macrophage apoptosis
1. OxLDL derived metabolites are toxic (eg 7-keto cholesterol)
2. macrophage foam cells have protective system that maintain survival in face of toxic lipid overloading
3. when overwhelmed, macrophages die via apoptosis
4. release macrophage tissue factors and toxic lipids into central death zone called lipid necrotic core
5. thrombogenic and toxic material accumulates and walled off
6. platelet rupture and meet blood
237
what are macrophages' functions in atherosclerosis pathophysiology (6)
secrete inflammatory cytokines and chemokines
phagocytose, process and export cholesteral to reverse cholesterol transport
secrete oxidants that damage cells and LDL
accumulate cholesterol and become sick and activated by cholesterol overload
secrete MMPs to degrade fibrous cap collagen
initiate death of VSMC
238
what are characteristics of vulnerable and stable plaque in athersclerosis (4)
large soft eccentric lipid rich necrotic core
increased VSMC apoptosis
reduced VSMC and collage content
thin fibrous cap
infiltrate of activated macrophages expressing MMPs
239
signs and symptoms of atherosclerosis
death of downstream tissues
loss of function of one side of body (major ischeamic stroke)
severe central crushing chest pain with fear, dizzy, nausea (MI)
angina
thrombogenic and toxic material accumulate, walled off and plaque rupture and meet blood
240
what is nuclear factor kappa B (NFkB)
transcription factor
regulator of inflammation
241
what is NFkB activated by (3)
scavenger receptor
toll like receptor
cytokine receptors (IL-1)
242
roles of NFkB
bind and switch on numerous inflammatory genes (MMPs, IL-1, inducible nitric oxide synthase)
243
what does NFkB act as
non-redundant network hub in inflammation
244
what do NFkB do as a network
directs multiple genes (multiple different inflammatory stimuli including IL-1 and cholesterol crystals)
then coregulation of differnet inflammatory genes (eg IL-1)
245
what are the kinds of cardiomyopathy (3)
1. dilated cardiomyopathy and HF
2. Hypertrophic cardiomyopathy (HCM)
3. restrictive cardiomyopathy
246
mechanism of haemostasis
vessel constriction
formation of unstable platelet plug
primary haemostasis
stabilisation of plug within fibrin
secondary hemostasis
fibrinolysis
vessel repair and dissolution of clot
247
what is factor in indirect platelet adhesion
platelet bind to Glp1b on VWF
248
what is factor in direct platelet adhesion
platelet bind toGlp1a
249
after platelet adhesion, what is released (2)
ADP
thromboxane
250
causes of thrombocytopenia
bone marrow failure (leukaemia, B12 deficiency)
accelerated clearance (immune ITP, DIC)
pooling and destruction in an enlarged spleen
hereditary absence of glycoproteins or storage granules
acquired (drugs)
251
what is ITP (immune thrombocytopenia purpura)
not clot properly
immune system destroy blood clotting platelets
252
what is glanzmannn's thrombasthenia
absence of Gpllb/llla receptor on platelets
253
how aspirin lead to reduce platelet aggregation
block COX
254
mechanism of clopidogrel
antiplatelet medicine
blocks ADP receptor on platelets
255
does thromboxane A stimulate or inhibit platelet aggregation
stimulate
256
funciton of VWF in haemostasis
bind to collagen and capture paltelets
stabilise factor Vlll
257
does prostacyclin inhibit or stimulate platelet aggregation
inhibit
258
what are type 1 or 3 Von Willebrand disease
deficiency of VWF
259
what is type 2 Von Willebrand disease
VWF with abnormal function
260
what are 3 kinds of disorders of primary haemostasis
1. platelets
2. VWF
3. vessel wall
261
what are clinical features of disorders or primary haemostasis
bleeding
petechiae (bleed underneath skin)
ourpura (paltelet or vascular disorders)
severe VWD (haemophilia like bleeding)
262
tests for disorders or primary haemostasis
1. platelet count
2. platelet morphology
3. bleeding time
4. assays of VWF
5. clinical observation
* coagulation screen is normal
263
treatment for failure of production / function in abnormal haemostasis
prophylactic
therapeutic
264
treatment for immune destruction abnormal haemostasis
immunosuppression
splenectomy for ITP
265
additional haemostatic treatment examples
desmopressin (as AVP increase VWF and factor Vlll)
Tranexamic acid
266
what is role of coagulation in secondary haemostasis
genereate thrombin lla
267
role of thrombin lla
convert fibrinogen to firbin
268
causes of disorders of coagulation factor production
hereditary (factor Vlll/lX) haemophilia A or B
acquired (liver disease anticoagulant drug)
269
examples of anti coagulant drug
warfarin
direct oral anticoagulants (DOAC)
270
disorders of coagulation causes
deficiency in production
dilution (blood transfusion)
increased consumption (DIC,)
271
what is haemophilia
failure to generate fibrin to stabilise platelet plug
272
examples of acquired coagulation disorders
liver failure (decreased production)
anticoagulant drugs
dilution
273
which coagulation factor not synthesised in liver
VWF (in endothelial cell)
factor V (platelets)
274
clinical features of coagulation disorders
bruising
bleeding frequently restars after stopped
delayed and prolonged bleed after trauma
275
what are the clinical distinction between bleeding in platelet and coagulation defects
platelet/vascular: superficial bleeding into skin, mucosal membranes ; bleed immediate after injury
coagulation: bleed into deep tissues, muscles and joints ; delayed but severe bleeding after injury
276
tests for coagulation disorders
PT
APTT
FBC (platelets)
coagulation factor assays
277
which pathway does APTT test
intrinsic
278
which pathway does PT test
extrinsic
279
normal PT
prolonged APTT
haemophilia A/B
factor XI or XII deficiency
280
prolonged PT
normal APTT
factor Vll deficiency
281
prolonged PT
prolonged APTT
liver disease
anticoagulant drug (warfarin)
DIC
dilution
282
warfarin mechanism
inhibit Vit K
283
which clotting factors do Vit K affect
factors II, VII, IX and X and the anti-clotting proteins, proteins C and S
284
replacement of missing coagulation factors
FFP (contain all coagulation factors)
cryoptecipitate (rich in fibrinogen, factor Vlll, VWF, factor Xlll)
285
mechanism of tranexamixc acid
antifibrolytic
prevent excessive blood loss from major trauma
286
when can we use tPA (tissue plasminogen activator)
stroke to increase fibrinolysis
287
mechanism of heparin
anticoagulant
288
what is virchow's triad (3 factors predispose to thrombosis0
blood (venous thrombosis)
vessel wall (arterial thrombosis)
blood flow (both venous and arterial thrombosis)
289
examples of anticoagulant proteins(fibrinolytic factors)
protein C
protein S
antithrombin
290
what does factor C do in anticoagulant
inactive factor V
inactive factor VLLLa
291
what does antithrombin do
act on factor lla (prothrmobin)
292
does higher or lower blood flow incraese risk of thrombosis
reduced
293
treatment of venous thrombosis
anticoagulant (heparin)
lower procoagulant factors (use warfarin, DOACs)
294
mechanism of unfractionated heparin
anticoagulant
enhancement of antithrombin
(inactivate thrombin, factor X, factor IXa, XIa, XIIa)
295
differnece between heparin and warfarin
heparin: inject IV
warfarin: oral
296
mechanism of low molecular weight heparin (LWMWH)
contain pentasaccharide sequence to bind to antithrombin
297
do we needa monitor if use LWMH
no cuz predictable
298
action of warfarin
anticoagulant
Vit K antagonists (block recycling of Vit K)
inactive factor II, VII, IX, X, protein C and S
299
how to reverse warfarin action on Vit K (2)
1. Vit K administration (several hrs to work)
2. infusion of coagulation factor (PCC -- factor II, VII, IX, X/ FFP)
300
side effects of warfarin
blled
skin necrosis (protein C deficiency)
purple toe syndrome
embryopathy
301
what are the steps in coagulation (3)
initiation
propagation
fibrin formation
302
factor IIa role in fibrin formation
convert fibrinogen to fibrin
303
how to resistance to warfarin
lack patient compliance
diet, increase Vit K intake
reduce binding
304
which has renal impairment, warfarin or DOACs
DOACs
305
which has faster onset, warfarin or DOACs
DOACs
306
which need monitoring, warfarin or DOACs
warfarin
307
what does endothelium control
blood vessels function and tissues
tissue hoemostasis and regenration
308
what are organotypic properties
tissue specific
309
which cells have organotypic properties
endothelial cells
microvasculature
310
basic structure of blood vessels
a
Tunica adventitia
Tunica media
Tunica intimia
311
what is vasa vasorum
tiny vessels that feed larger vessels
312
structure of capillaries and venules
endothelium
mural cells (pericytes)
basement membrane
313
what is used to examine transcriptional signature of individual cells
single cell RNA sequence
to study expression of genes at single cell level
314
examples of tissue specific (organotypic) variations of microvasculature
fenestrated - kidney
non-fenestrated - lung, skin, muscle, BBB
discontinuous - liver
315
which factor does endothelial cells produce
angiocrine factors
316
what of endothelial cell does tissue specific microenvironment influence
phenotype
317
which type of cell is most abundant in heart and crosstalk with cardiomyocytes
endothelial cells
318
when resting, which pathways are endothelium at
anti-inflammatory
anti-thrombotic
anti-proliferative
319
when endothelium switched on to activated endothelium, what pathways are they on
pro-inflammatory
pro-thrombotic
pro-proliferative
320
how small tumors receive oxygen and nutrients
diffusion from host vasculature
321
how large tumors receive c=oxygen and nutrients
require new vessels
tumor cells secrete angiogenic factors to stimulate neovessel formation by endothelial cells
322
what is angiogenic switch
tumor cells secretes angiogenic factors that stimulate neovessel formation by endothelial cells in adjacent vessels
323
what is the most common hereditary bleeding disorder
VWF dysfunction
324
what is VWF disorder characterised by
mucosal bleeding
325
treatments for Von Willebrand disease
replacement therapy
(VWF, DDAVP)
326
role of VWF in haemostasis
1. mediates platelet adhesion to subendothelium and platelet aggregation
2. stabilise circulating coagulation factor VIII
327
role of VWF in angiogenesis
control angiogenesis byr egulating growth factor signaling (VEGFR2, Ang-2)
328
what happens when there is lack of VWF to blood vessels formation
increase angiogenesis
329
endothelial dysfunction in pathogenesis of atherosclerosis mechanism
1.leukocyte recruitment
2. permeability
3. shear stress
4. angiogenesis
330
leukocytes adhesion cascade mechanism
1. leukocytes interact with endothelium
2. leukocytes roll , stop, spread and enter
331
structure of capillary
endothelial cells surrounded by basement membrane and pericapillary cells (pericytes)
332
differnece between capillary and post-capillary venule
structure similar but post-capillary venules have more pericytes
333
what happens to leukocytes recruitment in athersclerosis
leukocytes adhere to activated endothelium of large arteries and get stuck in subendothelial space
334
what happens to monocytes recruitment in atherosclerosis
monocyte migrate to subendothelial space, differentiate into macrophages and become foam cells
335
are the flow patterns and hemodynamic forces same in vascular system
no
336
in straight parts of arterial tree, what is the blood flow described as
laminar
337
is the wall shear stress high or low in laminar flow and directional or indirectional
high
directional
338
in branches and curvatures of arterial tree, what is the blood flow described as
turbulent/ disturbed with non uniform distribution
339
is the wall shear stress high or low in disturbed flow and directional or indirectional
low wall shear stress
irregular distribution
340
what does laminar blood flow promote (4)
1. anti-thrombotic, anti-inflammatory
2. endothelial survival
3. inhibition of smooth muscle cells proliferation
4. Nitric oxide production
341
what does disturbed blood flow promote (4)
thrombosis, inflammation(leukocyte adhesion)
2. endothelial apoptosis
3. smooth muscle cell proliferation
4. loss of Nitric oxide production
342
protective effects of nitric oxide on cardiovascular system (6)
1. vasodilation
2. reduce platelet activation
3. inhibit monocyte adhesion
4. reduce SMC proliferation in vessel wall
5. reduce release of superoxide radicals
6. reduce oxidation of LDL cholesterol
343
what does angiogenesis promote
plaque growth
344
what does therapeutic angiogenesis prevent
damage post-ischaemia
345
how permeability contribute to early plaque formation
increased permeability to lipids increase early plaque formation
346
symptoms of upper respiratory tract infection
cough
sneeze
runny or stuffy nose
sore throat
headache
347
symptoms of lower respiratory tract infection
productive cough (phlegm)
muscle aches
wheezing
breathlessness
fever
fatigue
348
pneumonia symptoms
chest apin
blue tinting of lips
severe fatigue
high fever
349
risk factors of exacerbations of asthma pneumonia
respiratory infections
350
what is the most common cause of hospitalisation in pneumonia asthma
exacerbations
351
what are the common causative agents of respiratory infections for bacteria (4)
Streptococcus pneumoniae
Mycoplasma pneumoniae
haemophilus influenzae
mycobacterium tuberculosis
352
what are the common causative agents of respiratory infections for virus (35)
influenza A or B virus
respiratory syncytial virus
human metapneumovirus
human rhinovirus
coronavirus
353
mechanism of bronchitis
inflammation and swelling of bronchi
354
mechanism of bronchiolitis
inflammation and swelling of bronchioles
355
mechanism of pneumonia
inflammation and swelling of alveoli
356
what is the grading potential for bacterial pneumonia outside hospital
CRB65
confusion
respiratory rate ( >30breaths/min)
blood pressure (<90 systolic and 60 diastolic)
65 yo
357
what is the grading potential for bacterial pneumonia in hospital
CURB-65
confusion
urea (greater than 7mmol)
respiratory rate
BP
65yo
358
what are the bacteria that cause community acquired pneumonia
Streptococcus pneumoniae
mycoplasma pneumoniae
Staphylococcus aureus
Chlamydia pneumoniae
Haemophilus Influenzae
359
what are the bacteria that cause hospital acquired pneumonia
Staphylococcus aureus
Psuedomonas aeruginosa
E.coli
360
what are the bacteria that cause ventilator associated pneumonia
Pseudomonas aeruginosa
Staphylococcus aureus
enterobacter
361
bacteria that cause typical pneumonia
Streptococcus pneumoniae
Moraxella
Haemophilus influenzae
catarrhalis
362
bacteria that cause atypical pneumonia
Mycoplasma pneumoniae
Chlamydia pneumoniae
Legionella pneumoniae
363
what is typical pneumonia
most common
caused by most common forms of bacteria
364
what is atypical pneumonia
less frequent
distinct bacterial species
slower onset of symptoms and milder
365
what treatments are for bacteria pneumonia (2)
supportive therapy
antibiotics
366
what are supportive therapy for bacterial pneumonia
oxygen
fluids
analgesia
saline
chest physiotherapy
367
what are examples of antibiotics for bacterial pneumonia
penicillin eg amoxicillin
macrolides eg clarithromycin
368
mechanism of amoxicillin
beta lactams to bind proteins in bacterial cell wall to prevent transpeptidation
369
mechanism of clarithromycin
bind to bacterial ribosome prevent protein synthesis
370
treatment for CURB65 score 0
amoxicillin (clarithromycin or doxycycline if penicillin allergic)
371
treatment for CURB65 score 1-2
amoxycillin + clarithromycin
372
treatment for CURB65 score 3-5
benzylpenicillin IV + clarithromicin PO
373
what is opportunistic pathogen
a microbe that takes advantage of a change in conditions (often immuno-suppression)
374
examples of oropharynx bacteria
haemophilus spp
Staphylococcus aureus
Streptococcus pneumoniae
375
example of nose bacteria
staphylococcus aureus
strep pneumoniae
haemophilus spp
376
what is pathobiont
a microbe that is usually commensal but found in the wrong environment that can cause pathology
377
are the virus that cause respiratory infection pathobionts
no
378
how viral infection cause inflammatory response
airway narrowing
fluid and mucus build up in airways and parenchyma
damage to gas exchange surfaces
379
which virus has the most number of serotypes for common cold
rhinovirus
followed by coronavirus and influenza virus
380
H1N1 influenza A target
haemogglutinin binds to alpha2,6 sialic acid
381
H5N1avina flu target
haemogglutinin binds to alpha2,3 sialic acid
382
rhinovirus target
ICAM-1 (major)
LDLR (minor)
383
SARS-CoV-2 target
spike protein binds to ACE2
384
risk factor of bronchiolitis in infants (2)
premature birth
congenital heart and lung disease
385
what is leading cause of infant hospitalisation
Respiratory Syncytial Virus (RSV)
386
how Respiratory Syncytial Virus (RSV)
affect infants
infect infants
nasal flaring
chest wall retractions
hypoxemia and cyanosis
croupy cough
expiratory wheezing
prolonged expiration
tachypnea
387
what are the physical barriers of upper airway
hairs and cilia
388
physical and chemical barriers of epithelial lumen
fluid lining lumen
mucociliary escalator
epithelial barrier
389
immune fortification of host
innate immune responses
resident immune cell
recruited immune cell
390
characteristics of respiratory epithelium (5)
1. tight junctions
2. mucous lining and cilial clearance
3. antimicrobials
4. pathogen recognition receptors
5. interferon pathways to promote upregulation of anti-viral proteins and apoptosis
391
which interferon is essential in curbing new viral infections
IFN-1
392
examples of innate immunity cells (5)
1. alveolar macrophages
2. resident dendritic cells
3. neutrophils
4. natural killer cells
5. monocytes
393
function of CD8-T cells in adaptive immunity
provide antigen specific cytotoxic immunity and immunological memory
394
function of B cells in adaptive immunity
B cells differentiate into antigen specific antibody secreting cells and memory B cells
395
what are serotypes
pathogens which cannot be recognised by serum that recognise another pathogen
396
which part of respiratory tract is enriched for IgA
upper
have high frequency of IgA-plasma cells
397
which part of respiratory tract is enriched for IgG
lower
thin walled alveolar space allows transfer of plasma IgG into alveolar space
398
what are problems with too much IgG
inflammation and damage inXS surfaces
399
which virus has the most serotypes
rhinovirus
400
which virus require long lasting antibody mediated immunity
rhinovirus
401
which virus cannot be re-infected by same strain
influenza virus
402
how does influenza virus avoid antibody mediated immunity
influenza strains drift and shift surface antigens
403
which virus can have recurrent infection with the sam serotype or strain
Respiratory Syncytial Virus (RSV)
404
which virus has limited mutation of surface antigens
Respiratory Syncytial Virus (RSV)
405
why Respiratory Syncytial Virus (RSV)
can be re infected
natural antibodies wane rapidly allowing reinfection
406
which virus has no prior exposure
SARS-CoV-2
407
what are preventive / prophylactic treatment options for respiratory infection
vaccines (only work before or between infections)
408
examples of vaccine
major surface antigen (spike protein)
viral vector
mRNA vaccine
409
examples of anti-virals
remdesivir (broad spectrum antiviral) to block RNA dependent RNA polymerase activity
paxlovid (antiviral protease inhibitor)
casirivimab and imdevimab
410
which virus is most common cause of asthma and COPD exacerbations
rhinovirus
411
which pneumonia is high likelihood after viral infection
secondary bacterial pneumonia
412
which bronchiolitis is associated with asthma development
viral bronchiolitis
413
what are the 4 clinical parameters of murray score
1. PaO2/FIO2 (on 100% oxygen)
2. CXR
3. Positive end expiratory pressure (PEEP)
4. Compliance
414
which clinical readings in child can use to confirm a diagnosis of asthma
exhaled nitric oxide (FeNO)
415
what is intrinsic lung disease
alterations to lung parenchyma
interstitial lung disease
lung tissue becomes damaged and scarred
416
what is extrinsic lung disease
compress lungs or limit expansion
pleural
chest wall
neurotransmitter (reduced ability of respiratory muscles to inflate/deflate lung)
417
where is interstitial space
space between alveolar epithelium capillary endothelium
418
what is alveolar type 1 epithelial cells for
gas exchange surface
thin cells
419
what is alveolar type 2 epithelial cells for
surfactant tor educe surface tension, stem cell for repair
cell type regeneration (regenerate type 1)
420
what are fibroblasts component in lung parenchyma
produce ECM (collage type 1 etc)
421
alveolar macrophage function
phagocytose foreign material, surfactant
422
what are different types of interstitial lung diseases (6)
idiopathic (IPF,DIP)
autoimmune (CTD associated)
eposure related (hypersensitivity pneumonitis)
cysts or airspace filling
sarcoidosis
others (eosinophilia pneumonia)
423
what are some history of interstitial lung disease
1. progressive breathelessness
2. non-productive cough
3. limited exercise tolerance
4. occupational and exposure history
5. meds, FHx
424
what are some clinical examination of ILD
low oxygen sats
fine bilateral inspiratory crackles
digital clubbing
+/- features of connective tissue disease (skin, joints, muscles)
425
what are blood tests test for in ILD
ANA
rheumatoid factor
anti-citrullinated peptide
426
invetsigations in ILD
pulmonary function test
blood tests
6-min walk test
high resolution CT scan
bronchoscopy
surgical lung biopsy
427
what is lung physiology in ILD
scarring makes lung stiff
reduce lung compliance
reduce lung volume
reduce FVC
reduce diffusing capacity of lung for carbon monoxide
reduce arterial PO2 esp with exercise
428
how is FEV1/FVC ratio like in ILD
normal or increased
429
how is FEV1/FVC ratio in obstructive lung disease
reduced
430
why is high resolution CT (HRCT) good for ILD diagnosis
thin slices and high frequency reconstruction to give good resolution at level of secondary pulmonary lobule (which is the smallest functional lung unit on CT)
431
what color is high density substance in CT
white
as bone absorb more x-rays
432
what color is low density substance in CT
darker
air absorb few x-rays
433
what CT feature in ILD
honeycomb cysts
434
CT features in non-specific interstitial pneumonia
more inflammatory
ground glass type area
435
what is implied in honeycomb cysts in CT
no gas transfer in these areas
436
what are the general principles of ILD management early disease
pharmacological ( immunosuppressive drugs and antifibrotics)
vaccination 'smoking cessation
education, trials
treat co-morbidities
pulmonary rehabilitation
437
what are the general principles of ILD management late disease
supplemental oxygen
lung transplant
palliative care
438
what is idiopathic pulmonary fibrosis
progressive
scarring lung disease
unknown cause
439
name a serious event of IPF
acute exacerbations
contributes to 50% in hospital mortality
440
does IPF have a good or poor prognosis
poor
441
what are the predisposing factors of IPF (3)
genetic susceptibility
environmental triggers
cellular ageing
442
cellular ageing example that contribute to IPF
telomere attrition (shortening)
senescene
443
mechanism of IPF
aktered microbiome
cause injury to Type 1 and 2 alveolar epithelial cells
fail to regenerate
trigger fibrotic reaction
recruit and activate fibroblasts
XS accumulation of ECM
remodel and honeycomb cyst formed
fibroblasts further proliferate
cause scarring
444
what is spatial heterogeneity in IPF
area of normal right next to highly abnormal lung area
445
what is temporal heterogeneity in IPF
very active areas of fibrosis next to very inactive or less active fibrosis
446
do antifibrotics slow IPF progression or cure
slow disease porgresson
447
example of tyrosine kinase inhibitor
nintedanib
448
what is pirfenidone
inhibits TGF-β1-induced differentiation of human lung fibroblasts into myofibroblasts, thereby preventing excess collagen synthesis and extracellular matrix production.
449
what are the drug targets for fibrotic pathway
alveolar space
epithelium
mesenchyme
endothelium
vascular space
450
what is hypersensitivity pneumonitis (HP)
ILD caused by immune mediated response in susceptible and sensitised individuals to inhaled environmental antigens
451
which parts of lungs do HP involve (2)
small airways
parenchyma
452
what are the 2 types of HP
acute
chronic
453
what is acute HP
intermittent
high level exposre
mre abrupt onset
454
what symptoms are in acute HP
flu ike symptoms
4-12 hrs after exposure
455
what is chronic HP
low level exposure
nonfibrotic / fibrotic
456
what is non fibrotic chronic HP associated with
inflammatory
457
what is fibrotic chronic HP associated with
higher mortality
458
what are causes of HP
antigen exposure and processing by innate immune system
accumulation of lymphocytes and formation of granulomas
459
what are the inflammatory response mediated by in HP
T-helper cells
antigen specific immunoglobulin IgG antibodies
460
what are some diagnostic finding on auscultation of HP
inspiratory squeaks due to co-exisitng bronchiolitis and distal airway in HP are inflammed
461
what are some diagnostic finding on blood tests of HP
specific circulating IgG Ab
462
what are other diagnostic tests for HP
HRCT
bronchoalveolar lavage lymphocyte count
463
treatment of HP
corticosteroids
immunosuppressants (MMF, azathioprine)
antifibrotic (Nintedanib)
464
what is systemic sclerosis associated (SSc) ILD
autoimmune connective tissue
465
characteristic of SSc
immune dysregulation ajd progressive fibrosis that affect skin
variable organ involvement
466
who do SSc usually affect
young, middle aged women
467
how many % of SSc develops into ILD
30-40%
most common death
468
how are clinical features of SSc classified
based on skin involvement
469
2 types of SSc
1. limited cutaneous SSc (pulmonary hypertension more common)
2. diffuse cutaneous SSc (ILD more common)
470
what are the different features of SSc
sclerodactyly (skin tightening)
raynaud's (reduced blood flow to fingers)
telengectasias (dilated or broken blood vessels located near the surface of the skin or mucous membranes)
471
what are the autoantibodies associated with ILD
anti-centromere
anti-Scl-70
472
pathogenesis of SSc-ILD (step 1-6)
1. tissue injury
2.vascular injury
3.autoimmunity
4. fibrosis
5. inflammation
473
tissue injury causes in SSc-ILD
1.genetic predisposition
2. gastro-oesophageal reflux
3.oxidative stress
4. environmental stimuli
5. organic solvents
6. virus, silica
474
vascular injury causes in SSc-ILD
1. endothelial cell injury
2. tissue hypoxia
3. ineffective angiogenesis
475
autoimmunity causes in SSc-ILD
B cell differentiate to plasma cell to release auto antibodies and IL-6
IL-6 is the key in ILD
476
fibrosis causes in SSc-ILD
IL_6 stimulate fibrocytes recruited and resident fibroblasts activated
myofibroblasts express aSMA and produce collagen
cause inflammation at last
477
what is the most common pattern in SSc-ILD
non-specific interstitial pneumonia (NSIP)
478
management of SSc-ILD
corticosteroid is controversial as risk of renal crisis if high dosages
immunosuppressives
antifibrotic (nintedanib)
479
what is polychromatic macrocytes in terms of RBC
immature RBC
480
what does reticulocyte count increased indicate
anaemia
RBC destruction before mature
481
difference between haemolysis and haemolytic
haemolysis: increased destruction of RBC (reduced RBC survival)
haemolytic: RBC lifespan reduced
482
why give folic acid in anaemia
increased requirement for erythropoiesis
483
why do splenectomy in anaemia
increase RBC lifespan
484
what is DAT test for (Direct antiglobulin test)
detects immunoglobulin and/or complement on the surface of red blood cells
485
what is auto-immune haemolytic anaemia (AIHA)
immune system mistakes red blood cells as unwanted substance
486
disorders of immune system associated with AIHA (2)
systemic autoimmune disease (SLE)
underlying lymphoid cancers (lymphoma)
487
what are the bone marrow response to haemolysis
have reticulocytes
488
what are Heinz bodies
a type of hemolytic anemia, which happens when your red blood cells break down faster than your body can replace them
indicate oxidant damage
489
what is G6PD role
protect red blood cells from damage and premature destruction
490
G6PD deficiency results
cause red cells vulnerable to oxidant damage
result in haemolysis
491
what is haemolytic anaemia
shortened survival of red cells in circulation causing anaemia
492
causes of inherited haemolytic anaemia
G6PD deficiency
abnormalites in cell membrane/ Hb or red cell enzymes
493
causes of acquired haemolytic anaemia
extrinsic factors eg micro organism, chemicals, drugs, malaria
494
what is extravascular haemolysis
defective red cells are removed by spleen
495
what is intravascular haemolysis
acute damage to red cell
496
in inherited haemolytic anaemia, if the site of defect is membrane what example of anaemia is that
hereditary spherocytosis
497
in inherited haemolytic anaemia, if the site of defect is at haemoglobin what example of anaemia is that
sickle cell anaemia
498
in inherited haemolytic anaemia, if the site of defect is at glycolytic pathway what example of anaemia is that
pyruvate kinase deficiency
499
in inherited haemolytic anaemia, if the site of defect is at pentose shunt what example of anaemia is that
G6PD deficiency
500
in acquired haemolytic anaemia, if the site of defect is membrane what example of anaemia is that
AIHA autoimmune haemolytic anaemia
501
in acquired haemolytic anaemia, if the site of defect is at whole red cell mechanical what example of anaemia is that
microangiopathic haemolyic anaemia (MAHA)
502
in acquired haemolytic anaemia, if the site of defect is at whole red cell microbiological what example of anaemia is that
malaria
503
in acquired haemolytic anaemia, if the site of defect is at whole red cell oxidant what example of anaemia is that
drugs chemical
504
what are investigations for blood in stool
faecal immunochemical test (FIT)
505
what is ferritin
storage form of iron
506
role of hepcidin
inhibit iron absorption
507
what happens when reduce hepcidin
increase iron absorption and release storage iron
508
what is microcytic anaemia usually associate with in terms of color
hypochromic
509
what is macrocytic anaemia usually associate with in terms of color
normochromic
510
2 examples of microcytic anaemia with defect in haem synthesis
iron deficiency
anaemia of chronic disease
511
2 examples of microcytic anaemia with defect in globin synthesis
alpha and beta thalassaemia
512
lack in what results in megaloblastic anaemia
vit B12 and folic acid
513
