Respiratory Flashcards
(266 cards)
1
Q
What are some common VIRAL respiratory tract infections?
A
- common cold (coryza)
- sore throat (pharyngitis)
- Tonsillitis
- Sinusitis
- Laryngitis
- Croup
- acute bronchitis
- bronchiolitis
- influenza
- SARS
2
Q
What are some common URT syndromes?
A
- common cold
- pharyngitis/tonsillitis
- sinusitis
- otitis media
- epiglottitis
- croup
3
Q
What are the main actions of exogenous glucocorticoid use in asthma?
A
-decrease inflammatory cell number and activation
(via targetting IL-8, COX2, ICAM-1, NOS2)
-increases activation of anti-inflammatory effectors
(by activating GILZ, MKP-1, IkBalpha)
-decrease probability and severity of asthma episodes
4
Q
Exogenous glucocorticoid use in asthma targets what specific inflammatory cells?
A
- decreased activity and recruitment of eosinophils, macrophages, mast cells,
- decreased cytokine production by macrophages, smooth muscle and fibroblasts
- decreased collagen production by s muscle and fibroblasts
5
Q
What are the 2 main categories of glucocorticoids used in asthma?
A
- inhaled/topical
- oral/systemic
6
Q
What are some differences between inhaled and oral glucocorticoids?
A
Inhaled
- start at the effective dose and then step down
- well tolerated/few SE
- used in combination with LABAs
Oral
- either treat for several days for acute asthma or chronically for sever asthma
- there are dose limiting SE
7
Q
What are the side effects of inhaled glucocorticoids?
A
- dysphonia
- oral candidiasis
- decreased serum cortisol
8
Q
What are the side effects of oral glucocorticoids?
A
- osteoporosis
- diabetes
- muscle wasting
- HT
- growth suppression
- suppression of HPA axis
- eventual atrophy of the adrenal gland with chronic use
- if you suddenly stop them you can go into withdrawal
9
Q
Describe the regulation of endogenous glucocorticoids
A
cortisol (an endogenous glucocorticoid) is released from the adrenal gland where is negatively feedbacks to
- inhibit the hypothalamus from releasing corticotropin releasing hormone,
- it inhibits the anterior pituitary from releasing corticotropin
- inhibits the immune system and the CV system
10
Q
What other 2 drugs can be used to treat asthma other than glucocorticoids?
A
Methylxanthines (eg theophylline)
Phosphodiesterase inhibitors (eg roflumilast)
11
Q
Briefly explain the mechanism behind using theophylline for asthma
A
- PDE inhibition/ s muscle relaxant
- adenosine antagonism
- HDAC2 activation
12
Q
What are some side effects of using theophylline in asthma?
A
- nausea
- vomiting
- diarrhea
- CNS stimulation
- cardio stimulation–> dysthymia
13
Q
Describe the steps in asthma therapy
A
Step 1: intermittent inhaled SABA
Step 2: add mildly persistent inhaled glucocorticoid
Step 3: add moderate persistent inhaled LABA
Step 4: increase daily inhaled glucocorticoid, maintain daily LABA, plus theophylline, anti leukotriene and oral glucocorticoid
Step 5: add oral prednisolone
14
Q
What does GOLD stand for? What is it used for?
A
Global initiative for chronic Obstructive Lung Disease -its a way to classify the severity of airflow limitation in people with COPD
GOLD1= mild
GOLD2= moderate
GOLD3=severe
GOLD4= very severe
15
Q
The alveolar capillary membrane is composed of what
A
- layer of surfactant
- type 1 alveolar cells
- basement membrane (shared)
- vascular endothelial cell
16
Q
What are some characteristics of the alveolar capillary membrane?
A
- thin (o.5 microns)
- large SA= 50-100m2
- alveolar volume= 3-6L
- capillary volume= 80ml
17
Q
What are some diseases that can disrupt the alveolar capillary membrane?
A
- inflammation
- infection
- fibrosis
- emphysema
- fluid
- cancer
18
Q
What are the likely physiological effects of disrupting the alveolar capillary membrane?
A
- abnormal gas exchange
- abnormal lung mechanics
- pulmonary vascular complications
19
Q
Describe the diffussion of gases in the lungs
A
- diffusion is passive/non E requiring
- driven by diffs in partial pressures of gases on either side of the membrane
- rate of diffusion is driven by Ficks Law
20
Q
What is Ficks law?
A
The rate of diffusion is proportional to [AxD(P1-P2)]/T
21
Q
Compare the diffusion rate of CO2 to O2
A
CO2 diffusion rate is 20x that of O2
22
Q
Describe the diffusion of Oxygen
A
- very fast
- 0.75 secs at rest
- 0.25 secs during exercise
- there is built in redundency (i.e. if we decrease transit time e.g. in exercise, there is still enough time for adequate diffusion of O2)
- NB normal gas exchange is not diffusion limited, but it in disease states gas exchange is diffusion limited
23
Q
Describe the phrase: diffusion limitation of oxygen transfer
A
- oxygen transfer can be diffusion limited in disease states
- if the a-c membrane is grossly abnormal in severe disease O2 transfer is diffusion limited at rest
- in moderate disease the O2 transfer is only diffusion limited during exercise
24
Q
Describe the diffusion of carbon dioxide
A
- its similar to O2 but 20x faster
- diffusion limitation only occurs in very severe abnormalities of the membrane
- when there is an elevated PaCO2 it is due to inadequate alveolar ventilation (VA)
- PaCO2 is inversely proportional to alveolar ventilation
25
What are some causes of low PaO2?
- low PiO2
- low ventilation
- abnormal gas exchange (via low V/Q, shunt or diffusion impairment)
26
What are some causes of a high PaCO2?
Low ventilation
27
What are the effects of restrictive lung disease?
- increased sensation of breathing
- increased elastic WOB
- decreased lung volume
- altered pattern of breathing
- decreased max ventilation
- abnormal gas exchange that worsens during exercise
28
Describe the mechanism behind increase sensation and WOB in restrictive lung disease.
Inspiration muscles need to generate higher Ps to overcome the stiffness (decreased compliance/ elastic WOB). This leads to
- recruitment of accessory muscles
- increased O2 consumption if resp muscles
- risk of muscle fatigue--> ventilatory failure
29
What happens to the FVC, FEV1 and FER in restrictive lung disease?
FVC is reduced
FEV1 is reduced
FER is normal (because FVC and FEV1 has decreased in proportion)
30
Minute ventilation is proportional to what...
metabolic activity
31
Describe the type of breaths people take when they have stiff lungs
rapid and shallow breaths
32
In people with restrictive lung disease exercise is often limited by what?
- hypoxia
| - pulmonary HT
33
What reduces surface tension in the alveoli and what happens as a result to this?
- surfactant
| - increases the compliance
34
What are the parameters that describe ventilatory failure?
PaO2 50mmHg
35
What is idiopathic pulmonary fibrosis?
- a fatal interstitial lung disease
- mean survival= 3 years
- aka usual interstitial pneumonitis
- scarring thickens and stiffens alveolar walls leading to impaired oxygen transfer, increased WOB, resp failure
- drugs used: pirfenidone (TGFbeta modifier), nintedanib (triple kinase inhibitor)
36
What are the types/causes of pulmonary arterial hypertension?
- idiopathic
- familial (mutation in BMPII receptors)
- secondary (chronic hypoxia from: pulmonary fibrosis, COPD, altitude)
37
What are some treatments for PAH?
Endothelin receptor antagonists
-bosentan, sitaxentan, ambisentan
Prostanoids (prostacyclin analgoues)
PDEI
-sildenafil
38
What is a systematic review?
- lit review that focuses on 1 question
- steps= identify, selection&appraisal, synthesis
- has well defined criteria
- reviews clinical trials and observational data
- its the highest level of evidence
39
What is a meta-analysis?
- statistical aspect of a systematic review
- derives pooled weighted average effect sizes
- its more quantitative than systematic reviews
- it mainly takes experimental data
- it functions to summarise the current lit, increase the power of results, resolve uncertainty, increase precision and answer other questions
40
What does the identify step in performing a systematic review consist of?
- define a clear question
- look at PICOT parameters
- search databases using MESH terms and relevant spelling
- look at other reference lists
- look at grey literature
- adopt inclusion/exclusion criteria
41
What does the selection&appraisal step in performing a systematic review consist of?
- done by at least 2 independent ppl
- read all abstracts
- apply inclusion and exclusion criteria
- look at full paper
- access for quality
42
What does the synthesis step in performing a systematic review consist of?
-perform a meta-analysis
43
Describe what a forest plot is?
-quick way to understand systematic reviews
-squares= inidividual studies
area of the square= sample size
horizontal line in the square= CI
verticle line in the square= RR
-diamonds= pooled effects
horizontal width= CI
vertical width= weighted effect size
-line of null effect
44
What is heterogeneity and what are the different types?
Heterogeneity= a test to determine how different the studies being compared are to each other
- p value>0.05 is good here because it says the studies are similar enough to be pooled i.e. they have failed the heterogeneity test
- types: statistical heterogeneity, non-statistical heterogeneity
45
What is statistical heterogeneity?
- measures effect/outcome
| - its quantitative
46
What is non-statistical heterogeneity?
- aka methodological/situational heterogeneity
- use PICOT
- its qualitative
47
What are some common LRT infection syndromes?
- acute bronchitis
- acute exacerbation of chronic bronchitis
- bronchiolitis
- pneumonia (acute bacterial, atypical, others)
- empyema
- lung abscess
48
What causes acute exacerbations of chronic bronchitis?
bacterial infection on a compromised lung
- strept. pneumococci
- H. influenzae
49
What causes bronchiolitis?
-RSV
50
What causes acute bacterial pneumonia?
- pneumococci (community derived pneumonia)
- H. influenzae
- staph (hospital derived pneumonia)
- Klebs (hospital derived pneumonia)
- legionella
- TB
- chlamydophila
51
What causes atypical pneumonia?
- mycoplasma
- chlamydia
- M. catarrhalis
- influenza
- RSV
- adenovirus
52
What causes other pneumonia?
Fungi
- Histoplasma
- Aspergillus
- Pneumocystis
53
What causes lung abcesses?
- mixed anaerobes
- Staph
- Klebs
54
What causes empyema?
-staph. aureus
55
How do you treat pneumonia?
- you need to distinguish between community derived and hospital acquired
- look at the severity index
- look at any underlying illnesses
- look at RFs
- determine the type of specimen to see if AB treatment is appropriate
- Pen G/amoxycillin plus doxycycline/macrolide
- vaccines
56
What are some common causes of the common cold?
- rhinovirus
- parainfluenza virus
- RSV
- enterovirus
- coronavirus
- human metapneumovirus
57
What are some causes of epiglottitis?
-H-influenza type b
58
What are some causes of croup/laryngio-tracheal bronchitis?
- parainfluenza virus
- influenza A
- RSV
59
What are some causes of otitis media?
- pneumococci
- H.influenzae
- M.catarrhalis
60
What are some causes of sinusitis?
```
primary= viral
secondary= h.influenzae and strept. pneumoniae
```
61
What are some causes of pharyngitis/tonsillitis with nasal involvement?
not likely to be bacterial
- adenovirus
- enterovirus
- parainfluenza virus
- influenza virus
62
What are some causes of pharyngitis/tonsillitis without nasal involvement?
- adenovirus
- influenza
- enterovirus
- reovirus
- strept. pyogenes
- strept. C
- strept. G
63
What is a tropism?
the anatomical localisation of an infection
64
List some common routes of entry for viruses
- paraenteral inoculation
- skin
- conjunctiva
- respiratory tract
- ailmentary tract
- urogenital tract
65
What are some barriers in the ailmentary tract that viruses need to overcome?
- sequestration in intestinal contents
- mucus
- stomach acidity
- intestinal alkalinity
- proteolytic enzymes form pancreas
- bile
- IgA
- scavenging macrophages
66
What are some barriers in the respiratory tract that viruses need to overcome?
- mucus
- cilia
- alveolar macrophages
- temperature gradient
- IgA
67
What are some different mechanisms of viral spread in the body?
- local spread on epithelial surfaces
- subepithelial invasion and lymphatic spread
- via the bloodstream
- infects the foetus
- infects the baby at birth
68
Describe the different types of viremia
Free in the plasma viremia
- produced by infected vascular endothelium or released from the liver and spleen
- neutralised by Ab and removed by macrophages
- there are 2 stages: 1st small numbers, 2nd large numbers
Cell associated viremia
- can persist if the viral genome becomes latent
- avoids CD8 attack when latent
69
What determines a tropism?
- availability of receptors
- optimal temp
- stability in extremes of pH
- ability to replicate inside macrophages and lymphocytes
- polarised release
- presence of activating enzymes
70
What are some types of viral induced damage to tissues?
- loss of function
- initiation of apoptosis
- death of cells directly form viral replication
- death from toxicity of viral products
71
What are some signs of immunopathology?
- fever
- IL-1, TNF
- increased size of LNs
72
List some targets for viral evasion strategies
- Ab
- Ab and T cells
- T cell priming by DCs
- CD8 cell recognition
- complement
- NK cell recognition
- Interferon
- Apoptosis inhibition
- cytokines
73
Describe how viruses evade Abs
-antigenic variation in B cell epitopes by antigenic drift
74
Describe how viruses evade Abs and T cells
latency
75
Describe how viruses stop T cell priming by DCs
- blockage of cytokine induced maturation of T cells
- virus encoded homologue of cytoplasmic tail of TLR4 therefore no signal transduction
- blockage of T cell stimulation
76
Describe how viruses evade CD8 T cell recognition
- Ag variation in CD8 epitopes
- inhibition of proteosome
- decreased MHC I expression or transcription
- inhibition of viral peptide release from the ER
- inhibition of processing and presentation
77
Describe how viruses evade complement
-viral encoded homologues
78
Describe how viruses evade NK cell recognition
- virus encoded MHC I like molecule
- upregulation of non-classical class I molecules
- mutations in ligand for activating receptor
79
Describe how viruses evade interferon
-interfere with PKR pathway by small RNAs, ds RNA binding proteins, PKR binding proteins
80
Describe how viruses evade cytokines
- virus encoded cytokine receptor homologues
- intracellular blocking of cytokine production
- intracellular interference with cytokine function
81
What are some factors that affect susceptibility to viral infections?
Genetic
- inherited defects
- receptor genes
- IFN inducible genes
- polymorphisms in genes controlling immune responses
Non-genetic
- age
- malnutrition
- hormones and pregnancy
- dual infections
82
What are the types of outcomes of a viral infection?
- fatal
- full recovery
- recovery but permanent damage
- persistent infection
83
What are the stages of viral replication?
- Attachment
- Penetraction
- Uncoating
- Gene transcription
- Assembly
- Release
84
Describe each step of viral replication
Attachment
-via carb or protein receptors
Penetration
-by fusion or endocytosis
Uncoating
Gene transcription
-DNA viruses replicate in the nucleus
(protein synthesis)
--early proteins are nonstructural
Assembly
-spontaneous or proteolytic cleavage
Release
- lysis
- budding for enveloped viruses
- secretatory pathway for golgi derived enveloped viruses
85
What are type I pneumocytes?
- make up the majority of the SA
- they are the exchange surface
- have tight junctions
- simple squamous
86
What are type II pneumocytes?
- 5% of SA
- more numerous
- cuboidal cells
- short microvili
- lamellar bodies produce surfactant
- can replace itself or produce type I pneumocytes
87
Describe the order of cells in the blood gas barrier from the alveolar lumen to the blood plasma
- alveolar lument
- surfactant
- type I pneumocyte
- basal lamina
- CT
- basal lamina
- endothelial cell
- plasma
88
Describe the structure of a bronchus
- thinner walls than the trachea
- cartilage plates
- s muscle between lamina propria and submucosa
- glands
- lymphoid nodules
89
Describe the structure of a brionchiole
- NO cartilage
- 1-2mm diam
- resp epithelium loses goblet cells and ciliated columnar cells
- gains clara cells
- radial CT
- s muscle
90
Describe the structure of a terminal brionchiole
- final level of the conducting system
- NO goblet cells
- 1-2 layers of s muscle
- clara cells
- cuboidal epithelium
- cilia
91
Describe the structure of a respiratory brionchiole
- alveoli start to appear--> alveolar ducts
- epithelium is cuboidal to squamous
- intermittent wall
92
Describe the structure of an alveolus
- 200um in diam
- simple squamous epithelium
- wall contains capillaries
- alveoli are connected by pores
- interalveolar septum
93
Describe the process of inspiration
- stimulation of the diaphragm by phrenic nerves C3,4,5
- stimulation of external intercostal muscles by intercostal nerves
- increase volume of the thorax
- negative intrapulmonary P
- sucks air into lungs
94
Describe the process of expiration
- passive
- inspiratory muscles relax
- elastic recoil of lungs
- generates a positive intrapulmonary P
- pushes air out
95
In a normal person FEV1 should be what % of FVC?
-greater than 70%
96
Describe the FVC, FEV1 and FER in people with airflow obstruction
FVC is normal but it takes longer to get there
FEV1 is smaller than 70% of FVC
FER is smaller than 70%
97
Why is it important to match ventilation and perfusion?
Because this is when gas exchange is most efficient
98
What diseases commonly have V/Q mismatch?
-COPD and asthma
99
What are the diff types of V/Q mismatch?
- Low V/Q units
| - Shunt
100
What is the compensatory mechanism done by the body in response to a V/Q mismatch?
- vasoconstriction in areas of low V in order to reduce the hypoxaemic effects
- this can lead to increased pulmonary artery P
101
What is the alveolar-arterial gradient?
-a measure of the overall efficiency of gas exchange across ALL A-C units
```
PAO2= PiO2 - (PACO2/RQ)
PiO2= 150
PACO2= PaCO2 from blood gas results
RQ= 0.8
```
gradient= PAO2-PaO2
PaO2 from blood gas results
normal gradient <15-30
102
In order to breath what 2 forces must you overcome?
- resistive force
| - elastic force
103
What does hypoxaemia mean?
-decreased O2 content of the blood which leads to decreased O2 in the tissues
104
What does hypercapnemia mean?
-increased CO2 which leads to respiratory acidosis
105
What are the normal blood gas and pH parameters?
PaO2 ~100mmHg
PaCO2= 40mmHg
pH= 7.40
106
What are the different types of validity?
Internal validity
- how well did it answer the q?
- how did the study deal with bias and confounding?
External validity
- generalisability
- use PICOT
107
Describe intention to treat analysis and what it attempts to minimise
- you assume the subjects remained in the group to which they were originally randomised to, regardless of cross over or drop out
- is decreases selection bias
108
Describe CI for HR, OR, RR
it must NOT include 1
109
Describe CI for absolute risk diffs
it must NOT include 0
110
What are some types of errors?
- Type I error (alpha)
| - Type II error (beta)
111
What is a type I error (alpha)?
When a study says there is an effect when in actual fact there isn't one
-its due to bias and confounders
112
What is a type II error (beta)?
When the study says there is no effect when in actual fact there is one
-its due to the study not having enough power (small sample size)
113
Describe number needed to treat
-the number of people needed to undergo the intervention in order to prevent the outcome in one person
NNT= 1/absolute risk or rate reduction
114
Briefly describe the inflammation present in asthma
- Th2 cells
- mast cells
- eosinophils
- some neutrophils
- mucus hypersecretion--> mucus plug
- vasodilation
- bronchoconstriction
- sensory nerve activation
- oedema
- increased vascularity
- increased subepithelial collagen thickening
115
What are the 4 major groups of hypersensitivity?
Type I: immediate hypersensitivity
Type II: antibody mediated
Type III: immune complexes
Type IV: delayed type
116
Describe the 2 phases of a type I hypersensitivity reaction
Sensitisation phase
- DC and IL-33
- Basophil and IL-4
- TH2
- IgE and FCERI
Effector phase
- immediate phase (release of preformed mediators)
- delayed phase (lipid mediators)
- late phase (cytokines)
117
What are some treatments for type 1 hypersensitivity?
- epinephrine
- inhaled beta agonists
- corticosteroids
- antihistamines
- desensitisation therapy
118
Describe delayed type hypersensitivity
- cell mediated
- via TH1, IFN-gamma and macrophages
- has a sensitisation phase
- Ag persistance--> accumulation of T cells and macrophages
- 3 examples: contact hypersensitivity, TB and Celiac disease
119
Describe contact hypersensitivity
-requires previous exposure
-Ag haptenates to a protein that is normally presented in MHC
-re exposure triggers memory cells and increased IFN-gamma
Eg poison ivy, TB test, eye drop allergy
120
Describe mycobacterium tuberculosis
- inhalation of TB droplet
- multiplication inside resident alveolar macrophages
- cytokine production (IL-12, TNF-alpha, IL-1)
- limited degradation
- macrophages and DC migrate to the LN--> present TB Ag to T cells
- activated CD8, TH1 cells produce IFN-gamma --> further activate macrophages
- persistence of TB--> cyclic cycle--> granuloma formation
121
Describe celiac disease
- to gliadins
- >90% are DQ2 positive
- DQ2 peptide binding cleft is positively charged and therefore binds negatively charged aa
- gliadins are rich in glutamine
- unmodified gliadins bind POORLY
- gliadins modified by tissue transglutaminase 2 cause glutamine--> glutamate
- can now bind in pocket, presented in MHC II--> effector TH1 response--> IFNgamma--> damage to intestinal wall
122
Where are mast cells located?
At sites in contact with the external environment
123
What are some signals for mast cell degranulation?
- poly basic drugs
- morphine
- vancomycin
- allergen
- stings
- activated complement
- neuro peptides
- hypertonic saline
- osmotic stimuli
- UV light/heat
- mechanical stimulation
124
Describe the degranulation process of mast cells
- allergen binds to already bound IgE
- cross linking
- brings FceR1 subunits tog (1alpha, 1beta, 2gamma)
- lyn tyrosine kinase phosphorylates the ITAMS and other proteins
- syk tyrosine kinase is recruited--> activated-->produces--> DAG and IP3
- DAG activates PKC--> granule movement and membrane fusion
- IP3 increases intercellular calcium--> membrane fusion and cytokine gene expression
125
Describe the 3 phases of the mast cell response
Immediate
-preformed mediators
(Histamine)
Delayed
-synthesised mediators
(Cys-LTs, PGD2)
Slow
-changes in gene expression
126
What are some actions of histamine
Acting on H1
- increase in vascular permeability
- vasodilation
- mucus secretion
- bronchospasm
- pain and itch
- increased wakefulness
Acting on H2
- positive inotropic and chronotropic
- gastric acid secretion
127
What are some inhibitors of mast cell activation?
- PGE2
- NSAIDs
- COX2 selective inhibitors
- cortisol
- adrenaline
- disodium cromoglycate/ nedocromil sodium
- omalizumab
128
What are some inhibitors of mediator production and actions
- glucocorticoids
- H1 receptor antagonists
- cysteinyl leukotriene receptor antagonists
129
Describe the actions of glucocorticoids
- induces annexin 1
| - decrease mast cell cytokine production
130
Describe the actions of cysteinyl leukotriene receptor antagonists
Eg montelukast
| -bronchodilator
131
Describe the 3 generations of H1 receptor antagonists
1st gen
-sedative
2nd gen
- non sedative
- poor CNS entry
- lacks anti muscarinic activity
- can cause arrhythmias
3rd gen
- newer
- non sedative
- decrease cardiac events
132
Crepitations indicate what 2 possible pathological processes?
-fluid in the lungs
or
-fibrosis
133
What are the 2 main consequences of abnormalities of the pulmonary vessels?
- increased movement of fluid out of pulmonary capillaries and into the alveoli
- increased P within the pulmonary vessels
134
Describe some characteristics of the pulmonary circulation
- low P ~15mmHg
- low resistance
- mostly at the level of the heart
- thin walled vessels, RA and RV
- acts as a reservoir for blood
- pooling of blood occurs on inspiration
- during ex, pulmonary artery P does NOT increase with increased CO b/c of dilation and recruitment of pulmonary vessels
135
What are the factors that determine fluid movement across the pulmonary capillaries?
Starlings forces
- Hydrostatic P inside (Pc) and outside (Pi) the cap
- Oncotic P inside (Oc) and outside (Oi) the cap
- Permeability of the capillary
net fluid out= K[(Pc-Pi)-permeability(Oc-Oi)]
136
What happens to fluid that is in the lungs?
Normally there is fluid movement from the caps--> interstitium--> which is then removed by lymphatics. However if this process if overwhelmed and the interstitial fluid rises too high then it will seep into the alveoli
137
What are the effects of pulmonary oedema on lung function?
Mechanical effects
- decreased lung compliance
- decreased lung vol
- increased airway resistance
- increased WOB
Gas Exchange effects
-hypoxaemia due to shunt, low V/Q, and diffusion impairment
Arterial blood gases
- decreased PaO2 and PaCO2, increased pH
- if v severe then increased PaCO2 and decreased pH
Pulmonary circulation
-increased pulmonary vascular resistance
138
What are the 2 main causes of pulmonary oedema?
- increased capillary hydrostatic P
- increased capillary permeability
exaggerating factors= decreased colloid osmotic P, decreased lymphatic drainage
139
Distinguish between diagnostic and screening tests
Screening test
- identify patients who may have the disease
- high sensitivity (low FN)
- need to confirm the results with a diagnostic test
- applied to ppl with no clinical suspicion of disease
- problem= it will include FP
Diagnostic test
- confirmation of the disease or otherwise
- high specificity (low FP)
- applied to ppl who have a clinical suspicion of the disease
- problem= it will exclude FN
140
Define sensitivity and its formula
= % of ppl with the disease that test positive
Sensitivity= TP/ (TP+FN)
141
Define specificity and its formula
= % of ppl without the disease that test negative
Specificity= TN/ (TN+FP)
142
Define positive predictive value and its formula
= % of the positive tests that are truly positive
PPV= TP/ (TP+FP)
143
Define negative predictive value and its formula
= % of the negative tests that are truly negative
NPV= TN/ (TN+FN)
144
PPV and NPV depend on what factors:
-sensitivity
-specificity
-underlying prevalence of the disease
(PPV is proportional to the prevalence, NPV is inversely proportional to the prevalence)
145
What are likelihood rates
-they measure the likelihood that a test result would be expected in a patient with the disease compared to a patient without the disease
LR of a positive test= sensitivity/(1-specificity)
LR of a negative test= (1-sensitivity)/specificity
146
Describe the phrase "trade off between sensitivity and specificity"
- Test results are given arbitrary thresholds to define the presence of disease
- if we lower the threshold--> sensitivity increases and specificity decreases
- if we increase the threshold--> sensitivity decreases and specificity increases
147
Describe ROC curves
- determines how well a test discriminates people with the disease form people without the disease
- plot 1-specificity vs sensitivity for various thresholds
- its a graphical rep of the tradeoff between sens and spec
- you measure the AUC to determine the quality of the test
0. 9= excellent quality
0. 7=fair
0. 5= fail, no discrimination
148
What are some limitations of screening?
- sometimes they are not cost effective
- SEs
- selection bias
- lead time bias
- length time bias
149
What is lead time bias?
-when a test detects the disease earlier and gives the impression of prolonged survival when actually the outcome of the disease is unchanged
150
What is length time bias?
-its more likely to detect non aggressive disease (e.g. slow growing tumours e.g. prostate cancer because the person has lived long enough to be screened and those with more aggressive forms have died before being screened)
151
What are the names of the divisions of a bronchus?
- mainstem
- lobar
- segmental
- subsegmental
152
Describe the cell types found in bronchi-->brionchioles
- resp epithelial cells (tall pseudostratified cilliated columnar cells)
- goblet cells
- neuroendocrine cells
- basal cells
153
Describe the cell types found in alveoli
- alveolar macrophages
- type I and II pneumocytes
- fibroblasts
- inflammatory cells
- endothelial cells
154
List some obstructive lung diseases
- asthma
- COPD (chronic bronchitis, emphysema, small airways disease)
- bronchiectasis
155
List some restrictive lung diseases
- idiopathic pulmonary fibrosis
- pneumoconiosis
- sarcoidosis
- honey comb lung
156
What is the definition of emphysema?
- abnormal, permanent enlargement of air spaces distal to the terminal bronchiole
- desctruction of the alveolar wall WITHOUT fibrosis
157
What is the definition of chronic bronchitis?
-persistent cough, productive of sputum for at least 3 months in 2 consecutive years
158
Describe the morphology of chronic bronchitis
- hypertrophy of mucus secreting goblet glands (xs mucus)
- increased lymphocytes, macrophages and plasma cells
- oedema
- peribronchial fibrosis in small airways
- possible squamous metaplasia
159
Describe the definition of small airways disease
- caused by cigarette smoke
- chronic inflammation
- fibrosis
- obstruction of terminal brionchioles
- its a component of COPD
160
What is the definition of bronchiectasis?
- irreversible
- abnormal dilation of bronchi/bronchioles
- dilated airways are full of pus
- severe destructive inflammation
- loss of surrounding elastic tissue--> airway collapse and obstruction
161
What are the symptoms of bronchiectasis?
- SOB
- cyanosis
- episodic fever
- severe cough with foul smelling sputum
162
What are some causes of bronchiectasis?
- necrotising infections (Staph aureus, influenza, aspergillus)
- obstruction which increases the risk of infection
- CF
- cilia disorders
- non-infectious inflamm conditions (CT diseases, graft vs host disease)
163
Define restrictive lung disease
A group of diverse conditions that have these features:
- chronic, diffuse, non-infectious
- restrictive spirometry
- inflammation and fibrosis of the inter-alveolar septa
- diffuse reticulo-nodular and or ground glass apperance on a CXR
164
Describe the symptoms of typical influenza
- fever/chills
- cough
- headache
- muscle aches
- fatigue
- loss of appetite
CXR is normal
165
Who are the at risk groups for seasonal influenza?
- the young
- the elderly
- those with underlying chronic conditions
166
Briefly describe the life cycle of seasonal influenza
- infected droplets from coughing or sneezing enter RT
- virus binds to sialic acid containing receptors (alpha2-6 linkage to galactose) on non-ciliated resp epithelium via Hemagglutinin (HA)
- receptor mediated endocytosis via a clatherin coated pit
- endosome becomes acidic, HA changes confirmation to expose fusion region--> fusion of viral envelope with endosomal membrane
- 8 RNPs escape
- travel to nucleus and viral RNA synthesis and mRNA synthesis occurs
- viral protein synthesis and glycosylation in ER--> golgi (allows surface expression of HA and NA)
- viruses bud out of cell
- NA cuts sialic acid receptors on surface so newly formed viruses don't attach back to the dying cell
- typtase Clara cuts HA and now the viruses are infectious
167
Describe the pathogenesis of seasonal influenza
- infected droplet enters RT
- infects non cilliated resp epithelium via sialic acid receptors
- replicates in URT and LRT but predominately in large airways
- tissue damage
- cytokines and IFN
- IL1--> fever
- IFN--> malaise, head and muscular aches
- pre-existing or developing immunity is now sufficient to clear the virus
- NB later in infection viral replication can occur in ciliated epithelium of trachea and bonchi--> increased risk of secondary bac infection--> death from bac pneumonia
- or infection can occur within the lung parenchyma--> primary viral pneumonia
168
Describe the time course of seasonal influenza infection
- acute infection
- 7 days or longer
- no persistence of virus BUT cough and weakness may last for several weeks
- incubation period= 1-5 days
- infectious period= 5-6 days
169
Describe the structure of influenza
- from the orthomyxoviridae family
- enveloped
- segmental genome (8 segments)
- ss -ve sense RNA
- HA and NA on surface
- M 1 and 2 channels
- Non structural protein= anti IFN activity
170
What are some types of influenza viruses?
Influenza A
- further divided into subtypes based on the form of HA and NA they encode
- 16 diff HA, 9 diff NA
- only type that can also infect other species
- causes human influenza
Influenza B
-causes human influenza
Influenza C
-minor human pathogen
171
What are the functions of HA and NA in influenza?
HA= the gripper (trimer)
NA= the snipper (tetramer)
172
What influenza subtypes have recently circulated in humans and which are circulating currently?
- H1N1, H2N2, H3N2
| - H1N1, H3N2 are currently circulating
173
Despite there being sialic acid containing receptors throughout the body why is influenza confined to the respiratory tract?
- because cleavage of HA can only be done by typtase Clara which is only released by Clara cells in the respiratory tract
- trytase Clara cuts HA and releaves a hydrophobic fusion peptide
174
Describe the adaptive response to influenza
CD8 cells
- kill infected cells
- important in recovery
- immunity is not long lived but can be boosted by repeat exposure
- doesn't stop the infection just controls it
Abs
- speeds clearance of virus
- inhibits attachment or release of virus
- Ab and complement mediated lysis of infected cells
- promotion of phagocytosis
- immunity is long lived
- they stop infection unlike CD8 cells
175
Briefly describe antigenic drift in relation to influenza
- it leads to the creation of new strains within a subtype
- single a.a change because of errors in replication= drift
- the change can be deleterious, neutral or advantageous
- its advantageous if they occur at sites on HA and NA where neutralising Abs bind
- i.e. Abs may not be able to bind any more and so viruses with these mutations will be selected for= antigenic drift
176
Briefly describe the life cycle of seasonal influenza
- infected droplets from coughing or sneezing enter RT
- virus binds to sialic acid containing receptors (alpha2-6 linkage to galactose) on non-ciliated resp epithelium via Hemagglutinin (HA)
- receptor mediated endocytosis via a clatherin coated pit
- endosome becomes acidic, HA changes confirmation and exposes fusion region--> fusion of viral envelope with endosomal membrane
- 8 RNPs escape
- travel to nucleus and viral RNA synthesis and mRNA synthesis occurs
- viral protein synthesis and glycosylation in ER--> golgi (allows surface expression of HA and NA)
- viruses bud out of cell
- NA cuts sialic acid receptors on surface so newly formed viruses don't attach back to the dying cell
- typtase Clara cuts HA and now the viruses are infectious
177
What are some targets for vaccine induced immunity and for antiviral drugs in the life cycle of influenza?
- Ab attachment to HA (prevents attachment to host cell)
- Ab to NA blocking efficient release
- ion channel (M2) blockers (prevents acidification of endosome and therefore endosomal escape)
- NA inhibitors
178
Name 2 antivirals that are used to block M2 ion channels in influenza
- amantadine
| - rimantadine
179
Briefly describe the difference between antigenic drift and antigenic shift
Antigenic drift
- it leads to the creation of new strains within a subtype
- gentle changes
- single a.a change because of errors in replication
- its advantageous only if they occur at sites on HA and NA where neutralising Abs bind
- i.e. Abs may not be able to bind any more and so viruses with these mutations will be selected for
Antigenic shift
- big changes
- sudden appearance of an influenza A virus of a new HA and sometime NA
- the new HA is often from birds
- results form genetic reassortment using the mixing vessel (pig) because they contain both the human alpha2-6 linkage and the avian alpha2-3 linkage
180
Describe the influenza vaccine
- inactivated trivalent vaccine
- inactivated--> only induces Ab responses not CD8
- contains 3 diff influenza viruses (influenza A H1N1, H3N2 and influenza B)
- administered intramuscularly
- grown in fertilised eggs (therefore not for ppl with allergies)
- needs to be updated each year because of emerging new strains
181
What subtype is the avian flu?
H5N1
182
What are the effects of pulmonary (artery) HT?
- increased RAP
- increased systemic venous P--> peripheral oedema, ascites, pleural effusion, right HF if severe
- RV dilation and hypertophy as compensation but this further increases systemic venous P
183
What are some causes of pulmonary HT?
- increased pulmonary BF
- increased LA pressure
- increased pulmonary vascular R (MOST IMPORTANT)
- -vasoconstriction to compensate for low PAO2
- -obstruction
- -obliteration
184
What is the compensation for Respiratory acidosis?
Bicarbonate retention
185
What is the compensation for metabolic acidosis?
Hyperventilation (lower PaCO2)
186
What is the compensation for respiratory alkalosis?
Bicarbonate excretion
187
What is the compensation for metabolic alkalosis?
mild hypoventilation
188
Where is the respiratory control centre located?
brain stem
- in the pons and medulla
- major output is via the phrenic nerves
- generate automatic rhythm
cortex
-voluntary control
189
Describe the different types of respiratory sensors
Central chemoreceptors
- on medulla
- surrounded by CSF
- CSF [H+] reflects CO2 in cerebral capillaries
- increased PaCO2--> increased CSF [H+]--> increased ventilation
- doesn't respond to PaO2
Peripheral chemoreceptors
- in carotid bodies and aortic bodies
- respond to decreased PaO2, decreased pH and increased PaCO@--> increased ventilation
- rapid response
Lung and other receptors
- pulmonary stretch, irritant, J receptors
- upper airway receptors, joint and muscle receptors, painful stimuli
190
What are some causes of hypoventilation?
- reduced respiratory centre activity
- neuromuscular disease
- chest wall deformity
- obesity
- sleep disordered breathing
- as a consequence of resp muscle fatigue, secondary to severe lung disease
191
Describe the ventilatory response to hypoxia?
-there is no change in ventilation until PAO2 is below 50-60mmHg
192
Describe the ventialtory response to exercise
- ventilation increases with work to maintain PaO2 and PaCO2
- beyond the anaerobic threshold, relative increases in ventilation are because the body is trying to correct the extra H+ production form lactic acid
193
What are the types of sleep disordered breathing?
- obstructive sleep apnoea
- central sleep apnoea
- obesity hypoventilation syndrome
194
Define breathlessness
-arises when there is a recognition by a subject of an inappropriate relationship between respiratory work and total body work
195
What are some systems approaches to dyspnoea
- respiratory
- cardiac
- muscle weakness
- metabolic
- anaemia
- psychogenic
- MUD (medically undiagnosed dyspnoea)
196
What are some respiratory causes of dyspnoea
- airways disease (upper or lower)
- alveolar disease
- pulmonary vascular disease
- pleural and chest wall disease
- respiratory muscle disease
197
What millennium development goal number realtes to TB?
goal 6
198
Describe how the socioeconomic gradient relates to TB risk?
-the poorer you are the greater the risk you have for having TB
199
Define pneumonia
Any inflammation of the lung
200
Describe 2 patterns of acute bacterial pneumonia
acute bronchopneumonia
- patchy
- often involves more than 1lobe
- coughs up purulent sputum
- fibrin and neutrophil rich exudate
acute lobar pneumonia
- inflammation in the entire lung
- red hepatisation--> gray hepatisation
201
What is a lung abscess?
Collection/cavity of pus
Caused by:
-aspiration
-obstruction of bronchial tree
-bac pneumonia
-acute bronchopneumonia in debilitated hosts
-haematogenous seeding of the lung from an extra pulmonary infection
202
Describe viral pneumonias
- they don't produce consolidation
- can cause bronchiolitis and inflammation of the alveolar septa (lymphocytic rather than neutrophils)
- most are cytoplasmic which predisposes ppl to secondary bac infections
- lungs appear heavy, wet, red or boggy
203
Describe 2 examples of chronic infections of the lungs
Bronchiectasis
- dilation of large cartilage containing airways from scar tissue deposition around bronchi--> weakening of the bronchial wall by inflammation
- permanent
- poor drainage--> recurrent bac infections and abscesses
- haemoptysis
- copious offensive sputum
Pulmonary TB
- granulomatous inflammation and caseous necrosis
- type 4 hypersensitivity rxn
- forms tubercles
204
What are 3 types of pulmonary TB?
Primary TB
- in ppl previously unexposed
- middle lung segments
- gohn focus
- gohn complex
- self limiting
- healing by fibrosis
Secondary TB
- person has already had the disease Ir there is a reactivation of primary TB
- apical lung segments
- more severe
Miliary TB
- numerous small granulomas
- like little seeds
- can disseminate to other organs = haematogenous
205
Distinguish between thrombus and clot
Thrombus = solid mass of blood components formed DURING LIFE
clot= same but formed POST MORTEM
206
Where can venous thrombi form?
In any vein: superficial or deep
Majority are in DEEP veins of the LOWER LIMBS
207
Describe the histology of a venous thrombus
- red bc if RBC
| - layered (alternating levels of platelets to RBCs with fibrin throughout)
208
What factors in virchows triad are most important in predisposing to venous thrombosis?
Changes in blood constituents (hypercoagulability states)
Changes in BF
209
What are some types of primary hypercoaguability states?
(Genetic)
-factor V Leiden mutation (prevents activated protein C from binding to a cleavage site)
-prothrombin III deficiency
- antithrombin III deficiency
- protein C deficiency
- protein S deficiency
210
What are some types of secondary hypercoagulable states.
- surgery
- trauma
- burns
- malignancy
- obesity
- smoking
- hyper oestrogenic states
- nephrotic syndrome
- anti phospholipid Ab syndrome
211
What are some fates of venous thrombi?
Lysis
Organisation
Recannulisation
Embolism
212
What is an embolus?
A mobile mass of material within the vascular system able to lodge within a vessel, occlude it's lumen and onstruct BF
Thromboembolus= detached piece of thrombus
- most arise from deep veins in leg
- can travel to the right side of the heart and enter the pulmonary arterial circulation via the pulmonary artery
213
Describe the characteristics of pulmonary thromboembolism
- effects depends on size of the occluded vessel
- vein from the outside looks red with pale areas
- coiled shape (reflects vein of origin)
214
What is the name for an embolism lodged at the bifurcation of the pulmonary artery
Saddle embolus
215
What is the major consequence of a small pulmonary thromboembolus? And what does it look like?
Pulmonary infarction
- sharply demarcated
- wedged shaped
- base is on pleura
- red
- occluded artery is at the apex
216
What clinical signs does a patient present with if they have a small pulmonary thromboembolus without infarction?
Unexplained tachycardia and RFs for PE
217
What is sleep?
A behavioural state characterised by decreased awareness of the external environment, decreased reactivity to stimuli but with capability to return to wakefulness
218
What are some reasons we sleep?
- health and survival
- learning and brain development
- repair and maintenance
- clearance of metabolites
- E preservation
- avoid nocturnal hazards
219
What are the top 3 common sleep problems?
- obstructive sleep apnoea
- insomnia
- restless leg syndrome
220
How do you evaluate sleep?
```
Via polysomnography (PSG)
-looks at EEG, EOG, EMG
```
221
What is a hypnogram?
A graphical representation of sleep
222
What are some common characteristics of a PSG during wake time
Eye movements
High levels of muscle activity
High frequency EEG (alpha and beta waves)
223
What are some characteristics of a PSG during stage 1 and 2 sleep?
No eye movements
High muscle activity
Lower frequency of EEG (theta waves with sleep spindles and k complexes)
224
What characteristics are on a PSG during stage 3 sleep?
No eye movements
Variable levels of muscle activity
Low frequency on EEG (delta=SWS)
225
What are some characteristics of a PSG during REM sleep?
REM
low level of muscle activity
Higher frequency EEG (theta)
226
What are some cardiovascular changes that occur during sleep?
HR decreases
BP decreases
CO decreases
Metabolic activity decreases
227
What are the theories behind arousals from sleep?
Homeostatic vs reflex activation
The evidence supports a waking reflex
- adaptive reflex
- provides and evolutionary advantage
228
What does a person with obstructive sleep apnoea's hypnogram look like?
Minimal SWS
| No REM sleep
229
Describe the regulation of circadian rhythms
Controlled by suprachiasmatic nucleus (SCN)
Zeitgeibers= time givers act as external cues. Eg light inhibits the SCN, a lack of light increases melatonin --> promotes sleep
230
Describe the 2 process model of sleep
```
Homeostatic process (process S)
-drives sleep
```
```
Circadian process (process C)
-drives arousal
```
When the 2 process are furthest apart sleep happens. When someone is sleep deprived their amount of SWS and total sleep time increases
231
How does a lack of sleep impair performance?
- slows rxn time
- reduced vigilance
- slower info processing
- reduced short term memory
232
Briefly talk about sleep restriction and deprivation and how one acclimatises to it therefore impairing their subjectiveness
Sleep restriction has a cumulative effect on performance.
The more someone is sleep deprived the more they cannot accurately assess their sleepiness
233
What are the 3 functional neurobiological systems that control sleep?
Arousal systems
- within pons/midbrain
- inhibits sleep promoting system
Sleep promoting system
- VLPO (ventrolateral pre-optic nucleus)
- inhibits Orexin neurons and ariusal systems
Orexin neurons
- in hypothalamus
- projects onto arousal system
234
Describe species level selectivity
-Antimicrobials
-diffs in ribosomes, membranes, cell wall, enzymes and DNA allow selectivity
Eg sulfanilamide and trimethoprim act on the folic acid synthesis pathway at diff points
235
Describe cell level selectivity
- killing cancer cells
- methotrexate inhibits dihydrofolate reductase
- it has no effect on bac because they have a diff enzyme
- it's an anti cancer drug at high doses
- it's immunosuppressive at lower doses
- it's teratogenic
236
Describe organ level selectivity
- A combo of a diuretic and a angiotensin system inhibitor with an NSAID leads to acute renal failure via prostaglandin mediated vasodilation to preserve BF in response to hypoxia
- paraquat a herbicide but also a lung killer because it oxidises other molecules and makes ROS--> damage to membranes, proteins and DNA. Selective to the site of application
- gentamicin causes nephrotoxicity and ototoxicity. (Inhibits protein synthesis)
237
What are the 2 main types of neoplasia?
- benign
| - malignant
238
Paediatric cancers are given what general term?
Blastomas
239
Distinguish between benign and malignant
Benign
- local expansile
- slow growing
- well circumscribed
- can be encapsulated
- well differentiated
- unable to metastasise
- rarely life threatening
Malignant
- locally invasive
- destructive growth
- poorly circumscribed
- induce desmoplasia in the stroma they invade
- can have necrosis due to tumour outgrowing its blood supply
- variable differentiation
- potential to metastasise
240
What are the ways tumours can spread?
- lymphatic
- transcoelomic
- haematogenous
241
What are the histopathologic features of neoplasia?
Cytological atypia
- larger nuclei
- pleomorphic nuclei
- coarser nuclear chromatin
- hyperchromatic nuclei
- larger nucleoli
- more mitotic activity
Architectural disorganisation
242
What are the main categories of cell lineage in neoplasia?
epithelial cells
- gladular
- squamous
- endocrine
mesenchymal
-smooth muscle
others
243
Describe tumour terminology
Prefix= line of differentiation or cell lineage
- adeno= glandular
- squamous cell
- leiomyo= smooth muscle
- osteo= osteoblastic
Suffix
- oma= benign
- carcinoma= epithelial (malignant)
- sarcoma= mesenchymal (malignant)
244
Describe the types of degree of differentiation in cancer
-the extend to which tumour cells resemble their normal counterparts histologically
Well differentiated
- resemble mature cells
- less cytologic atypia
- less mitotic activity
- architecturally more organised
Poorly differentiated
- poorly resemble mature cells
- more cytologic atypia
- more mitotic activity
- archietcurally less organised
245
Distinguish between bening tumours and malignant tumours degree of differentiateion
-benign tumours are well differentiated
- malignant tumours may be well differentiated, moderately or poorly differentiated or anaplastic
- degree of differentiation of a malignant tumours is referred to its grade
246
Define the term premalignant lesion
- aka dysplasia or intraepithelial neoplasia
| - = abnormal growth
247
What are the major cancer characteristics of cancer?
- resisting cell death
- inducing angiogenesis
- enabling replicative immortality
- activating invasion and metastasis
- evading growth suppressors
- sustaining proliferative signalling
248
What are the emerginc hallmarks and enabling characteristics of cancer?
Emerging hallmarks
- deregulating cellular energetics
- avoiding immune destruction
Enabling characteristics
- tumour promoting inflammation
- genome instability and mutation
249
What are the 4 classes of normal regulatory genes that are commonly mutated in carcinogenesis?
- growth promoting proto-oncogenes
- growth inhibiting tumour suppressor genes
- genes that regulate programmed cell death
- genes involved in DNA repair
250
What are some types of mutations in cancer?
- errors in DNA replication not repaired
- point mutations
- amplifications of oncogenes
- chromosomal rearrangements
251
Name a gene that commonly undergoes oncogenic amplification
N-MYC
252
Name a gene that commonly undergoes oncogenic translocation and fusion
BCR and ABL
253
What are the major cell proliferation pathways in cancer?
PI3K pathway
-can signal via Ras or independent of Ras
MAPK pathway
-always signal via Ras
254
What is loss of heterozygosity?
-the loss of normal function of one allele of a gene in which the other allele was already inactivated
255
The oncogenes Ras and Myc act on what cell cycle checkpoints
- G2 to M
| - G1 before S phase
256
What are some strategies to evade apoptosis
- reduced CD95 level (fas receptor)
- inactivation of death induced signalling complex by FLICE protein
- up-reg of BCL2 (anti-apoptotic)
- reduced levels of pro-apoptotic BAX resulting from loss of p53
- loss of APAF-1
- up-reg of inhibitors of apoptosis
257
Name the steps involved in metastasis
- detachment of tumour cells from each other (disruption of integrins, E-cadherin, beta and alpha caterin, connexin 43)
- degradation of ECM
- attachment to novel ECM components
- migration of tumour cells
258
What are some effects of metastases
- local lymphadenopathy
- bone pain
- hypercalcaemia
- jaundice
- seizures
- weight loss
- anorexia
259
What is paraneoplastic effects/syndromes?
effects not due to effects of the tumour itself
- cushings syndrome-ACTH (small cell LC, pancreatic C)
- inappropriate ADH syndrome- ADH (small cell LC)
- hypercalcaemia- PTH related protein (squamous cell carcinoma of the lung etc)
- hypoglycamia- insulin
- polycthemia- erythropoeitin
260
What are some clinical features of LC
- local effects of primary tumour: cough, haemoptysis, wheeze, dyspnoea, pneumonia, Pancoast's syndrome
- effects of metastases: bone pain, jaundice, seizures
- weight loss, anorexia
- paraneoplastic
261
Name some investigations for LC
Hx and examination
blood tests
- Hb level
- liver function tests
- tumour markers
- -prostate specific Ag
- -carcinoemryonic Ag (CEA)
- -alpha fetoprotein
Radiology
Endoscopy
Tissue sampling
- biopsy
- cytology
- histopathology
- molecular and cytogenetic techniques
262
What are the classification of lung carcinomas?
Non-small cell carcinoma
- squamous cell carcinoma
- adenocarcinoma
- large cell carcinoma
Neuroendocrine carcinoma
-Small cell carcinoma
263
What type of LC is the most common?
-adenocarcinoma
264
How do you stage cancer?
TNM system
- T= size
- N= LN metastases?
- M= metastases?
the TNM components are then combined to give a stage grouping with 4 stages
265
What are some treatment options for cancer?
- surgery
- radiotherapy
- chemotherapy
- targeted therapy (small molecules that inhibit GFs or tyrosine kinase, mAb that target specific proteins or receptors)
- others e.g. immunotherapies, bone marrow tranplants
266
Describe the EGFR mutations in LC
- a proportion of non-small cell carcinomas are EGFR mutations
- especially in young non or light smoking female asians
- targeted therapies= gefitinib, erlotinib
