adv editor Flashcards
Lung volumes
TLC
VC
FVC
RV -
TV -
FRC
FEV1 -
FEV1/FVC -
TLC - total lung capacity - take a full breath in
VC - vital capacity - if you exhale all the way to the bottom of the lungs
FVC = forced vital capacity - exhale as forcefully as you can
total volume you can move
RV - residual volume = TLC - VC
TV - tidal volume - breathing normally
FRC - functional residual capacity = TLC-TV
FEV1 - the air that comes out in 1 second
usually all of FVC comes out in 3 seconds
FEV1/FVC - forced expiration ratio
What is the formula for maximum ventilation
how much do we need at rest?
MV = FEV1 * 35
at rest need roughly 8L/min
What is the A-a gradient?
What is it a measure of?
What is the normal value, when do abnormalities occur
measure of gas exchange efficiency (takes a look at lung overall - how well O2 diffuses across)
A-a gradient = PAO2 - PaO2
PaO2 - measure
PAO2 estimate from ideal gas equation
Normal <15-30 (not 100% bc of shunts)
- abnormality means Pa is much lower -> not diffusing across
How do you measure PAO2
This is the pressure in the Alveoli - need to estimate with idea gas equation
PAO2 = PiO2 - PACO2/RQ
PiO2 - mean inspired O2 (at sea level = 150)
PACO2 - can just sub in PaCO2 (very efficient)
RQ = 0.8
What are normal values for PaCO2
What is normal for HCO3-
PaCO2 - 35-46mmHg
HCO3- 22-28mmol/L
Respiratory acidosis - what is it
Causes
Compensation
Signs
increase in CO2
decreased HCO3-CO2 ratio -> ↓pH
_Causes _
usually: ventilation issues - hypoventilation, or VQ mismatch
not perfusion (CO2 is usually ventillation-limited )
_Compensation _
kidneys preserve HCO3-
_Signs: _
↑CO2
Metabolic acidosis
- what is it
- causes
- compensation
- signs
“metabolic” - primary change is in HCO3-
↓HCO3- relative to CO2 -> ↓pH
_Causes _
loss of HCO3- (eg diarrhoea)
buffering
accumulation of acids in blood - diabetes mellitus (ketoacid)
tissue hypoxia -> lactic acid
_Compensation _
increase in ventilation to ↓CO2
Signs:
↓ CO2
↓ HCO3
Respiratory alkalosis
- what is it
- causes
- compensation
- signs
decrease in PCO2 - this increases HCO3-PCO2 ratio => elevating pH
_Causes _
hyperventilation
high altitude
_Compensation _
kidneys increase excretion of HCO3-
_Signs _
↓ CO2
Metabolic alkalosis
- what is it
- causes
- compensation
- signs
increase in HCO3-
increases: HCO3-CO2 -> ↑pH
_Causes _
excessive ingestion of alkalis
loss of acid gastric secretion by vomiting
_Compensation _
some respiratory compensation - to reduce alveolar ventilation, thus increase CO2
often none
Signs:
↑HCO3
What % of total O2 use is normal WOB
3%
What are the mechanical effects of airflow obstruction? (7)
Obstruction -> ↑friction in airways -> inspiratory muscles must generate higher negative P to overcome obstruction + expiration becomes active -> ↑restrictive WOB
- increased sensation of breathing
- increased respiratory muscle effort
- active exhalation
- prolonged inspiration + expiration (harder to exhale completely - ↓FEV1)
- altered pattern of breathing (↑restive WOB - long slow breaths)
- reduced maximum ventilation (↓FEV1 -> ↓FEV1*35)
- gas trapping
What is pulsus paradoxus?
normally during inspiration, systolic BP drops due to increased negative pressure in thorax - this pools blood in pulmonary system, and decreases CO -> decreases BP
then during expiration, systolic BP rises, as there are higher pressure in the thorax, pushing blood back to heart
normal variation in BP <10mmHg
pulsus paradoxus is >10mmHg (difference between systolic P at expiration and inspiration)
=> implies that there are greater negative pressures being produced during inspiration -> higher WOB
hard to use as clinical sign - hard to measure when someone agitated
Spirometry of obstructive airways disease?
Airflow obstruction - takes longer to get air in/out
↓FEV1 with the same FVC
FEV1/FVC <70% (forced exp ratio)
What is normal maximum ventilation? What is that in regard to what you need at rest?
How does it change with exercise?
What limits exercise
MV > 100L/min
=>12x that of rest
max exercise - still have ~30% unused MV
Exercise is limited by max HR
Gas trapping - what is its link to obstructive airways
signs of gas trapping
Gas trapped beyond obstructed airways - can be inhaled, but not exhaled
signs
- ↑TLC
↑RV
↑RV/TLC
decreases VC even though you are hyperinflated
Consequences of obstructed airways
Recruitment of accessory muscles (scalene, sternomastoid)
↑O2 consumption by respiratory muscles (can use 40-50% of O2)
risk of respiratory muscle fatigue -> limited window to treat
What is V/Q matching?
When can V/Q mismatch occur
How does matching happen
What effect do V/Q mismatches have on PaO2
Gas exchange - most efficient when ventilation matches perfusion in all A-C units
V/Q mismatch if non-uniform airway osbtruction (asthma, COPD, bronchiolitis)
Matchin: Low V/Q units (those getting less ventilation than perfusion) result in ⌡PaO2
vasoconstriction occurs here to match
When V/Q = 0 => shunt (won’t respond to supplemental oxygen)
Low V/Q units - most clinically significant cause of ↓PaO2 in clinical practice
high V/Q units - little effect on PaO2, just physiological dead space
What is most clinically significant cause of ↓PaO2 in clinical practice
V/Q mismatch
What effect may V/Q mistmatch have in extreme cases?
↑pulmonary artery pressure
- vasoconstriction in low ventilation areas - if this is generalised (asthma), get generalised constriction
Defining pathological features of restrictive lung diseases
inflammation and fibrosis of inter-alveolar septa (interstitium)
Definition of compliance in the lungs
What components are important
Change in Volume for a change in pressure
Components:
- tissue composition
- surface tension in alveoli
what changes to tissue composition lead to reduced compliance
fibrotic, inflammatory, malignant, infective processes
What are the gas exchange effects of restrictive lung disease?
What are the mechanical effects
Gas exhange:
- Abnormal exchange - worsens with exercise
Mechanical
- increased sensation of breathing
- increased elastic WOB
- reduced lung volumes
- altered pattern of breathing
- reduced maximum ventilation
what are the physiological efects of a disruption to the AC membrane?
Abnormal gas exchange
Abnormal lung mechanics
Pulmonary vascular complications, if enough of pulm bed is affected
what happens to gas exchange in restrictive lung disease, and why (O2 and CO2)
Diffusion - need integrity of AC membrane (thickness, surface area)
Get a diffusion limitation of O2 transfer (usually is limited by ventilation) (the graph where blood stays in capillar .25 or .75 secs)
Diffusion limitation for CO2 will occur with very severe abnormalities of AC membrane
Potential causes of
- low PaO2
- low PaCO2
low PaO2
- low inspired O2
- low ventilation
- abnormal gas exchange (low V/Q, shunt, diffusion impairment)
low PaCO2
- low ventilation
(abnormal exchange only in VERY severe disease)
why does restrive lung disease increase sensation of breathing? (breathlessness)
stiff lungs - increase elastic WOB - increase load on breathing
what happens to lung volumes in respiratory lung disease?
all lung volumes reduced
both ↓FEV1 and FVC => ratio stays constant
(can have both restrictive + obstructive => ↓FEV1/FVC + ↓FVC)
what pattern of breathing is seen in restrictive lung disease?
high frequency - rapid, shallow breaths
what happens to max ventilation in restrictive lung disease? why?
MV = 35 * FEV1
FEV1↓ so ↓MV
spirometry in restrictive lung disease
all lung volumes are reduced
↓FVC
↓FEV1
normal FEV1/FVC
what is asbestosis?
what type of lung disease
pathophysiology
histology
presentation
diffuse interstitial lung disease due to exposure to asbestos => restrictive
pathophys
- progressive, diffuse inflammation -> over time drives fibrosis > repair
- abnormal fibrosis of lung parenchyma -> disruption/destruction of AC membrane
histo
- areas of inflammation
- fibrosis/scarring
- asbestos bodies
presentation = 3C’s (clubbing, cyanosis, crepitations)
What is idiopathic pulmonary fibrosis?
type of lung disease
cause
histology
prognosis
restrictive lung disease (interstitial)
cause: unknown
histo
- interstitial inflammation
- fibrosis at various stages of development
prognosis
- inevitable progression to end-stage lung
- mean survival - 3 years
What normally happens to fluid in the lung?
How/why can oedema form
Normall - small amount of fluid leaks from capillary to interstitium (~5ml an hour)
(capillary endothelium is highly permeable to water, ions, small molecules)
=> this is drained by lymphaticflow (~20ml/hr)
if fluid leak >20ml/hr => oedema
- fluid accumulate in interstitium, then moves to alveoli
are alveoli normally wet or dry?
dry - epithelium actively pumps water back to intersitium
What are the 2 mechanisms that cause pulmonary oedema?
What are the 2 other mechanisms that theoretically could cause it
(1) increased capillary hydrostatic pressure (Starling’s law)
- increased pulmonary venous pressure, left heart pressure
(2) Increased capillary permeability
- toxins, sepsis, multiple trauma, aspiration of gastric acid etc.
Theoretically: ↓colloid osmotic pressure, ↓lymp drainage
= but these aggravate, not cause
signs of pulmonary oedema (CXR)
CXR
- Kerley B lines
- dilated interlobular septa
- dilated lymphatics
- Perihilar alveolar opacities
- ↑pulmonary vein size
Consequences of fluid in the lungs (4)
Mechanical changes - small, stiff lungs
Gas exhange abnormality - low V/Q units + shunt
Pulmonary circulation - ↓vascular resistance
Arterial blood gasses - type 1 resp initiall, then develop type 2
What mechanical changes are seen as a result of pulm oedema?
↓compliance,
↓lung vol,
↑airway resistance -fluid in airway, bronchioles are compressed,
↑wob
What changes in blood gasses are seen in pulmonary oedema?
type 1 respiratory failure initially
- ↓ PaO2
- ↓ PaCO2
- compensatory hyperventilation
- ↑ pH
- respiratory alkalosis - because of hyperventilation
then develop type 2 respiratory failure
- ↓ PaO2
- ↑ PaCO2
- ↓pH
- metabolic and respiratory acidosis
- metabolic: becaues of hypoxia - tissues start to produce lactic acid
- respiratory: can’t ventilate -> ↑CO2
Causes of pulmonary hypertension (broad) (3)
(1) Increased left atrium pressure (mitral stenosis, LVF)
(2) Increased pulmonary blood flow (left-to-right shunts, high flow states, excess central vol)
(3) Increased pulmonary vascular resistance (vasoconstriction, obstruction, obliteration)
What can cause increased pulmonary vascular resistance?
Vasoconstriction - low alveolar O2, hypoxia, muscle spasm
Obstruction - emobolism, primary pulmonary hypertension
Obliteration = loss of capillary bed
(interstitial lung disease - arteritis, emphysema, pulmonary fibrosis)
Consequences of pulmonary hypertension
if very severe - right ventricular dilatation + hypertrophy (afterload)
=> ↑systemic venous pressure (extravasation of fluid in tissues) - oedema, ascities
=> poor cardiac output (breathlessness)
Clinical signs of pulmonary hypertension
- right ventricular heave - feel beat of RV (just next to sternum)
- loud P2 and 4th heart sound
- pulmonary systolic ejection murmur
- right heart is dilated - cusps can’t come together, don’t have functional tricuspid anymore
- tricuspid pansystolic murmur -> incompetence
- sinus tachycardia - get decreased SV, so have to increase rate
- hepatomegaly
- ascites
how does smoking predispose to pulmonary infection?
- inhibits muco-ciliary escalator
- increases mucous (direct trigger)
- inhibits leukocyte function
- direct damage to epithelial layer
causes of hypoventilation (5)
- **Reduced respiratory centre activity **
- reduced drive (eg low CO2, high pH)
- suppression of activity (drugs, trauma, vascular accidents etc )
- **Neuromuscular disease **
- nerve paralysis (drugs, polio, Guillian-Barre, trauma..)
- muscle weakness (drugs, motor neurone disease, muscular dystrophy )
-
Chest wall deformity (gross)
- respiratory pump becomes inefficient
-
Obesity (gross)
- respiratory pump becomes inefficient
- **Sleep disordered breathing **
what are the types of sleep disordered breathing? Where is the abnormality
(1) Obstructive sleep apnoea - most common
* upper airway
(2) Central sleep apnoea
- main abnormality: brain stem
- several forms: eg Cheye Stokes breathing - delayed stimulus to brainstem
- management: manage underlying problem +/- CPAP/BiPAP
(3) Obesity hypoventilation syndrome
- combo: particularly diaphragm
- usually presents as ventilatory failure +/- RHF
- “sensitive” to supplemental O2
- manage: BiPAP, weight reduction
What are the consequences of chronic severe sleep apnoea
Must sleep
During sleep - you get hypoventilation (resetting of resp centre)
-
patient keeps waking due to inadequate stimulation (↓O2, ↑CO2)
brain “decides” that LR sleep deprivation is not tenable -> brain starts to accept a higher C O2 and lower O2 so that sleep can continue
this spills over into daytime -> day-time hypoventilation => hypercapnoea
what conditions cause day time hypoventilation
what are its consequences
day time hypoventilation (chronic severe sleep apnoea, severe COPD, severe pulm fibrosis, neuromusc disease)
=> chronic hypoxia, chronic hypercapnoea, compensated resp acidosis
chronic hypercapnoea - what controls ventilation
become dependent on hypoxic drive (not stimulated to ventilate by CO2)
- O2 is low because of chronic hypoventiliation
ventilation also stimulated by exercise, metabolic acidosis
why must you be careful when givin supplemental oxygen?
If someone has had chronic hypercapnoea - their drive to breathe will have swtiched from CO2 to O2
=> supplemental O2 brings PaO2 back up - can develop acute hypoventilation
only give enough O2 to bring them back to “their normal” - ~90-ish
don’t aim for 100 ish - then will dev acute hypoventilation
What is teh cycle of events in obstructive sleep apnoea
- Snoring in light sleep
- Complete obstruction (apnoea) in deep sleep
- some people have narrowing such that this occurs with light sleep
- Reduced blood O2, increased CO2 other stimuli
- trying to breathe against obstruction
- increasingly forceful breaths - icn WOB is another stimulus
- Brain “wakes” to lighter sleep (arousal)
- this takes some compared to while awake - sensing by brain is also depressed during sleep
- Muscles contract, airways opens, breathing recommences
- muscles regain tone, obstruction clears (at least partially)
- Back into deep sleep -> obstruct again
Often 60x per hour throughout sleep
management of obstructive sleep apnoea
- Nasal CPAP - continuous positive airway pressure
- applies positive pressure to upper airway during sleep
- pressure acts as splint to keep soft tissues apart - stops their collapse
- 85% compliance for moderate+ OSA
- Mandibular advancement splint - mouthguard
- brings jaw forward, base of tongue brought bwd, tends to stop it flopping back
- Surgery
- Lie on side
what is obstructive sleep apnoea?
Why does it occur?
Transient obstruction of the throat during sleep preventing breathing, and disturbing sleep
Obstruction occurs during sleep because of
- relaxed airway muscles - floppy throat (esp REM)
- throat already arrowed (obesity, tonsils etc)
- tongue falls backward (esp if supine)
Pathophys of Pulmonary embolism
Thromboembolus lodges in pulmonary circulation
Effects depend on: size of embolus, presence/absence of underlying lung and cardiovascular disease
Embolus leads to development of:
- hypoxaemia
- local pulmonary artery obstruction + widespread reflex vasoconstriction
- increases pressure in system
- RV stress -> dilation and contractile dysfunction
- platelets in thrombi can release TXa -> lead to vasoconstriction
- increases pressure in system
- Constriction of airways distal to bronchi
- decreased pulmonary compliance
- haemorrhage, loss of surfactant
- VQ mismatch -> acute pulmonary hypertension
Consequences of PE
Depends on the size
Large/numerous
- if >60% of vascular bed is occluded - sudden collapse + death
- acute cor pulmonale - dyspnoea, hypotension (↓LV output), cyanosis
- pulmonary hypertension in setting of underlying lung problem
Medium sized
- Dyspnoea, cough, acute cor pulmonale
- Pulmonary infarction (relatively uncommon - blood supply of lung )
Small sized
- may be clinically silent
- pulmonary infarction
- recurrent
- many small emboli over time -> chronic pulmonary hypertension + cor pulmonale
Pulmonary infarct
- lung blood supply
- why are infarcts rare, what makes them more likely
- path morphology
- signs
rare - dual blood supply:
- O2 comes in via bronchial arteries and pulmonary arteries (even though deox blood)
more common if there is pre-existing lung and/or cardiovascular disease (eg heart failure - bronchial supply is sluggish; COPD - already hypoxaemic)
typically seen as peripheral, wedge-shaped, haemorrhagic
tissue dies because there is not enough O2, but there is still blood there -> red infarct
Signs
- haemoptysis
- pleuritic chest pain (acute inflammation -> fibrous exudate -> chest pain)
- pleural friction run (from associated inflammation)
- pleural effusion (because of inflammation)
Where do you get a saddle embolus?
Pulmonary trunk + both R&L pulm arteries
Pulmonary infarct - histology
Early
- coagulative necrosis + inflammation
Heals same as MI - acute inflammation, granulation tissue, fibrosis + scar formation
Pathogenesis of lung cancer
what is the dysplasia-carcinoma sequence
- Smoke irritant -> epithelium undergoes squamous metaplasia
- stem cells -> stratified squamous cells instead of respiratory epithelium
- Carcinogens in smoke cause mutations in proto-oncogees and tumour suppressor genes -> **dysplasia **
- get increased nuclei at surface compared to normal squamous epithelium
- bit more disorganised
- get increased nuclei at surface compared to normal squamous epithelium
- carcinoma in situ - more atypical and disorganised
- these cells invade into underlying stroma -> **invasive carcinoma **
Morphology of lung cancer (path)
Typically:
- pale mass, irregular, often arising from bronchus
- often necrotic (left) - form cavities
- especially squamous cell carcinoma
- adeno: tend to be more peripheral
- enlarged hilar lymph nodes
What are consequences of blocked bronchi (lung cancer)
if bronchus is blocked -> can develop
- pneumonia - mucus is obstructed - good place for bacteria to grow
- collapse or bronchiectasis of distal lung
What are the lung cancer classifications?
Squamous cell carcinoma => squamous proliferation
Adenocarcinoma => glandular stem cells
Large cell undiff => undiff cells, but of epithelial type (ep’m proteins)
Small cell carcinoma => neuroendocrine origin
Squamous cell carcinoma histology
normally seen in the form of rounded centre of keratin in centre of tumour islands
joined by intercellular bridges
often a lot of eosinophilic cytoplasm (squamous cells - lots of cytoplasm)
Adenocarcinoma of lung histology
shows glandular differentiation
usual feature: malignant cells that try to form a lumen
sometimes no cells - see accumulation of mucous (with special stain)
large cell undifferentiated carcinoma of the lung - histology
lots of large cells
large pleomorphic nuclei - usually sheets of these larger atypical cells
undifferentiated - no glands, mucous, intercellular bridges, keratin
small cell carcinoma of the lung - histology
cells are small - not that big compared to RBC
don’t show typical features of malignancy
- small
- small nuclei
- not that pleomorphic
- fine chromatin
but have a “characteristic look”
Whatis the most common lung cancer?
Which ones are strongly associated wtih smoking?
Adenocarcinoma
Smokers: squamous, small-cell, large-cell
Targeted treatment for lung adenocarcinoma
Mutations in adenocarcinoma: EGFR (tyrosine kinase), ALK, K-RAS, B-RAF
Gefitinim, Erlotinib - inhibit EGFR tyrosine kinase
(different mutations in diff tumors - have to genotype)
