7. Airway Diseases: Obstructive and Restrictive Flashcards
OBSTRUCTIVE and RESTRICTIVE
OBSTRUCTIVE:
• Limitation of ____;
• Increased ____
• Due to ____ obstruction
RESTRICTIVE:
• Reduced ____ of lung parenchyma
• Decreased ____
• Reduced ____
ATELECTASIS:
• ____ of lung volume
• ____
• ____
The diseases that are obstructive are the ones that limit air flow
The obstructive diseases are the limitations of air flow, and as a result there is increased
resistance. this is due to partial or complete obstructions.
- 3 diseases related to obstruction in the ____.
- and one is related to pathology in the ____
What about restrictive diseases?
-These all result from a limitation of air flow,
-but restrictive diseases are due to reduced expansion of lung parenchyma.
example: If you have a lung and you stretch it to be the size of a football field, and that football field shrinks, because of ____, there is going to be a decrease in lung capacity.
One is going to have to work ____ to breathe and exchange gas.
finally will talk about atelectasis: collapse of lung resulting from loss of volume (result of of either obstructive or restrictive).
airflow resistance partial or complete expansion lung capacity compliance collapse/loss obstructive restrictive
bronchi
alveoli
fibrosis
harder
Lung volumes in Obstructive and Restrictive diseases • Tidal Volume (VT) • Inspiratory Reserve Volume(IRV) • Forced Vital Capacity (FVC) • Forced Expiratory Volume1 (FEV1) • Residual volume
- what is tidal volume of the lung?
-change in lung volume during ____ breathing. this is the volume you
are exchanging - what is inspiratory reserve volume?
-volume on top of the ____ on the graph. - forced vital capacity?
-the volume of air that you can breathe out ____. the max you can force out.
example: the capacity of your lung is about 6000mL
if you try as hard as you can, can you force out that much? no, bc if you do, your lung will collapse. the volume of air that you can force out is about ____. - Residual Volume: About ____ that you cannot breathe out no matter how hard
you try. - diference between FVC and FEV1?
what does the 1 signify? it is very important!
-its the volume of air that you can breathe out in ____.
example: so if you think about it, if someone has an obstructive disease (asthma) and the bronchioles are narrow, would they be able to breathe out? if they breathe in, they can breathe in ____ amount, but if they try to breathe out, they will breathe
out ____ than normal.
normal tidal volume forcibly 5L 1L
one second
full
less
Lung volumes in obstructive and restrictive diseases
Normal
• FEV1 ~ ____ L
• FVC~5.0 L
• FEV1/FVC ~ ____%
Obstructive
• FEV1 ~____L
• FVC~5.0L
• FEV1/FVC ~ ____%
Restrictive
• FEV1 ~____L
• FVC~3.1L
• FEV1/FVC ~ ____%
FVC: about 5L
FEV1: is about 4L
1. NORMAL
-difference between these two in a normal individual is about 8-%
- OBSTRUCTIVE
-in obstructive diseases, your ____ is the same because your lung is not undergoing
fibrosis.
-But your ____ is going to be less.
Ex: if you think about a kid with asthma, breathing when they whistle, its because their
airways are narrow so they’re breathings out less.
*their ratio will be much less around 26%. This number is going to be very low. but FVC
will be normal. * Compared to normal 80% this number is very low. - RESTRICTIVE
-If someone has a lung fibrosis, what will happen to total FVC? ____, because lung capacity is reduced.
-If they dont have obstruction in their airway, what will happen to the ratio? It will stay about the ____.
In restrictive, your ____ is less because, say you have fibrosis in lung, because there is no obstruction, the ratio is about the same, maybe a little bit ____.
4.0 80 1.3 26 2.8 90
FVC
FEV1
less
same
FVC
higher
OBSTRUCTIVE LUNG DISEASES: • Dyspnea/obstruction: • Emphysema (alveoli/acinus) • Chronic Bronchitis • Bronchiectasis • Bronchial asthma
But emphysema, is actually in acinus of ____.
- What is the mechanism of emphysema?
- In this situation, there is ____ in size of airspace distal to terminal bronchi.
alveoli
increase
Emphysema
• ____ increase in size of airspaces ____ to terminal bronchioles
• Destruction of ____.
• Increase in size • Doesn't occur because of fibrosis, but because of \_\_\_\_ of the alveoli wall • Centriacinar ○ Morphologically, affects the \_\_\_\_ part of the acinus § \_\_\_\_x more prevalent § Associated with \_\_\_\_ • Panacinar ○ \_\_\_\_ acinus ○ Not smoking associated ○ \_\_\_\_ basis • Diseases are common, but \_\_\_\_ > because you have to biopsy after you die • Alveoli has elastin fibers, if you think of millions of alveoli that are pumping out, when they pump out > push air through the bronchioles, and if these alveoli are not coming out > \_\_\_\_ can collapse ○ obstruction is not a direct obstruction, direct narrowing of the bronchiole, but is bc the alveoli are forcefully pumping air out and keeping bronchiole open and if they collapse theres no \_\_\_\_ and the bronchiole collapse.
permanent distal alveolar walls destruction central 20 smoking whole genetic
underdiagnosed
bronchioles
pumping action
- Blow up a balloon with air > let it go > flare out in the room until it deflates
- Millions of balloons, working at same time > all the air would go through this way
- What happens when expire: elastin fibers are ____, and as they contract they let the air ____
contracting
out
Emphysema
Destruction of ____
____
“Pink Puffer” • \_\_\_\_ • Normal \_\_\_\_ • Breathing through “\_\_\_\_” • Breathe more \_\_\_\_ • \_\_\_\_
• Emphysema > destruction of elastin > air is \_\_\_\_ inside the alveoli • The bronchioles are kept open by the pumping of the alveoli, initially, if you think of FVE1/FVEC ratio; the capacity of the lung stays about the \_\_\_\_, but because of obstruction > can get oxygen in, but cannot get the \_\_\_\_ out ○ Look at indiviudals > lung is \_\_\_\_ > barrel chest > because of expanded lung preventing chest from \_\_\_\_ ○ Pink Puffer § Pink - initial stages, no defect In oxygenation > normal O2 levels > breathe through pursed lips more frequently > hyperventilatew § Later stages: \_\_\_\_ position, trying to get last breahth out
elastin barrel chest dyspnea O2 pursed lips frequently hyperventilation
trapped same CO2 expanded contracting hunched over
Neutrophil Recruitment Elastase Release
• Neutrophil recruited in smokers > release \_\_\_\_ > destroys elastic fiber ○ If someone who smokes a lot, or a little > what's the difference? • Neutrophil release elastase, and tries to digest elastin > \_\_\_\_ ○ Counterbalanced by \_\_\_\_ (produced by \_\_\_\_) § Present in the \_\_\_\_ ○ Elastase that's prodcued because of smoke is trying to digest elastin, and then you have A1AT that is trying to put a break on this § If A1AT (antiprotease) wins > no emphysema • Genetic defect ○ Deficiency in producing \_\_\_\_ ○ Can develop emphysema even if they don't \_\_\_\_ • Reduced amount of AT in plasma > what happens if you start smoking > \_\_\_\_-effect of degrading elastin
elastase emphysema alpha1-antitrypsin liver plasma
A1AT
smoke
double
Emphysema
Centriacinar
Panacinar
• Centriacinar ○ Acini are \_\_\_\_ because of \_\_\_\_ of elastic fiber ○ Lower magnificiation > you see the holes • Panacinar ○ The whole lung is \_\_\_\_ ○ Anywhere you look you see these perforations • Lower power mag ○ Normal lung parenchyma up top ○ The spaces are because of elastin fibers that are destroyed because of the \_\_\_\_
larger
destruction
expanded
elastases
Clinical features of emphysema and treatment
• Clinical: • First symptom: \_\_\_\_ • \_\_\_\_/Barrel chest • \_\_\_\_ • Dyspnea, \_\_\_\_ Hb (Pink puffer) • Death due to: – \_\_\_\_ – \_\_\_\_
- Treatment:
- Stop ____
- ____ therapy
- ____
- ____ (see COPD)
- ____ (LVRS)• Clinical symptoms
○ Dyspnea - difficult to breathe
○ Weight loss/barrel chest
○ Pink puffers
○ Normal hemoglobin
○ Death: respiratory insufficiency, and RSHF (cor pulmonale)
• Treatment
○ Stop smoking - if disocvered early
○ Oxygen therapy
○ Broncholdilators
§ Main manifestation > ____ of bronchioles, bronchioles are not expanding
○ Antibiotics
○ LVRS
§ The lung volume is expanded > reduce it!
○ These treatments only work if disease has only progressed so far, if alveoli are ____, nothing you can do to get them ____
dyspnea weight loss hyperventilation normal respiratory insufficiency cor pulmonale
smoking oxygen therapy bronchodilators antibiotic lung volume reduction surgery
contraction
destroyed
back
CHRONIC BRONCHITIS
Clinical condition; excessive ____ secretion in the bronchial tree
• Persistent and productive cough:
– At least ____ consecutive months in ____ consecutive years.
- ____, urban dwellers and ____ cities.
- ____
- 20-25% ____ (40-60 years) in smog- ridden cities• So much mucus coming out of bronchioles > figure out why they have obstructive disease
• Clinical condition
○ Excessive mucus secretion from bronchial tree
• Major diff bt emphysema and CB
○ Emphysema is morphologicla defintion, here it’s a ____ definition
• If someone has a productive cough for 3 months in 1 year, followed by the same thing the following year
○ Doesn’t develop overnight, takes time for someone to develop
○ Initially, may be acute
• ____ is the same in both cases
mucus 3 2 cigarette smokers smog-ridden middle-aged men men
clinical
etiology
CHRONIC BRONCHITIS
Clinical condition; excessive mucus secretion in the bronchial tree
• L: normal bronchiole wall, and passage for airway to travel • M: mucus blocking the airway ○ Reduced \_\_\_\_ ratio • R: shows the lumen of normal bronchiole; mucus, cilia, and goblet cells ○ Also have mucus gland ○ CB: excessive mucus retention, \_\_\_\_ can get trapped in there § If bacteria is trapped, and \_\_\_\_ is damaged > defense mechanism of the lung will be compromised > develop \_\_\_\_ of the lung
FEV1/FVC
bacteria
cilia
infection
Pathogenesis
Cigarette smoking/Irritant:
- Hypertrophy of ____ glands in ____ and main bronchi
- Hyperplasia of ____ in ____
- Mucus plug of ____ lumen
- Airway ____.
- Poorly functioning ____
- Cough
- Goblet cell ____ in ____ airways.
- Inflammation of ____ walls/fibrosis
- Airway obstruction• As undergo hypertrophy, prodcue more mucus
• As a result of hypertrophy and hyperplasia > produce more mucus > plugs lumen of bronchiole > lung obstruction, poorly functioning cilia (if cilia is covered it will suck)
• The obstruction mainly happens in the ____ and bronchioles, but what happens in small bronchioles:
○ Goblet cell metaplasia, and inflammation of bronchiole walls/fibrosis
○ Obstruction occurs because of two things:
§ ____ that is produced in bronchioles/trachea
§ ____ and fibrosis of the smaller airway
□ Add together to give obstruction
mucus trachea goblet cells bronchi/bronchioles bronchial obstruction cilia
metaplasia
small airways
bronchiole
trachea
mucus secretion
inflammation
REID INDEX
• Ratio of thickness of ____ wall
• Normal: ____ or less
• Chronic Bronchitis: ____ or more
• IF someone had died from CB > the mucus gland is going to be \_\_\_\_ than in a normal individual • Ratio of thickness of gland/bronchial wall ○ Red - total bronchole wall; balck is mucus gland § Normal is 0.4 or less ○ In CB > more mcuus gland > take up a larger space > 0.5+ • Abnormal ○ Black arrows > mucus gland, and red > wall of bronchiole ○ Compared ot normal, the mucus gland is much larger > \_\_\_\_ of CB
0.4
0.5
larger
diagnostic
CHRONIC BRONCHITIS
• ____ in the large airways and ____ in the small airways.
• Inflammation: ____/____
• Small airway (lower) > inflammation/fibrosis ○ Seeing inflammaiton ○ Blue dots > inflam cells; depending on timing of inflammatino, either \_\_\_\_, or neutrophils and \_\_\_\_ • Larger airway (upper) > \_\_\_\_ of mucous gland
mucus hyper-secretion
contraction
neutrophils and macrophages/fibrosis
neutrophils
macrophages
thickening
Chronic Bronchitis: Clinical Features • Airway \_\_\_\_ (Reduced \_\_\_\_) • Persistent cough and mucus production • \_\_\_\_ (low O2 in blood) • \_\_\_\_ (high CO2 in blood) • Severe cases: \_\_\_\_:(Blue bloater) • With progression: – \_\_\_\_ – Cor Pulmonale – \_\_\_\_
Blue bloater: ____
Pink puffer: ____
• Blue bloater ○ Overweight ○ Coughing out mucus ○ As opposed to someone who has emphysema: pink puffer • If die: ○ Pulmonary hypertension ○ Cor pulmonale ○ Recurrent infection § Because cilia is damaged and problem with bronchioles
obstruction FEV1/FVC hypoxemia hypercapnia cyanosis pulmonary hypertension recurrent infection
chronic bronchitis
emphysema
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
These two diseases are known as ____ together.
could mean pure emphysema, pure chronic bronchitis, or a combo of both.
DEFINITION
1. Emphysema definition is ____: biopsy of lung will see alveolar septa is ____
and missing alveoli.
2. Chronic bronchitis: definition is ____: productive ____.
LOCATION
- Emphysema: ____
- Chronic Bronchitis: in ____
ETIOLOGY
____ for both
normal alveoli, normal acini
1. if there is chronic bronchitis: ____ of small bronchioles small
airways and if you move higher there is ____ in airways. and the lung
parenchyma volume is the ____ size therefor there is no change in ____.
2. emphysema, because the ____ are destroyed, the alveoli are not pumping air out of lung, you will get ____ of bronchiole and get ____ disease.
etiology is the same for both diseases, but ____ is totally diferent.
talks about picture on left about above pictures of people:
-you dont always get pure emphysema and pure CB patients. because etiology is the same, could be a ____, and thats why we refer to it as COPD. they coexist most of the time.
COPD anatomic destroyed clinical cough
acinus
bronchioles
smoking
fibrosis mucus production same FVC elastic fibers collapse obstructive
mechanism
mix
BRONCHIECTASIS
• ____ of one or more ____
• Destruction of muscle and ____ supporting
• Predisposing factors: Bronchial obstruction • \_\_\_\_ • Aspirated \_\_\_\_ materials • Localized to the obstructed lung segment
- Congenital:
- ____ (obstruction caused by mucus)
- ____ (Immunoglobulin deficiencies)
- ____ (Structural Abnormality in cilia)
- Pneumonia:
- Caused by ____ organisms (e.g. ____)
- ____
Difference:
here destruction is taking place at ____ whereas emphysema it is taking place at the acinus at the ____ level.
Predisposing factors: mostly ____.
1. bronchial obstruction: because of neoplasm, or aspirated foreign materials.
2. could be congenital if someone has cystic fibrosis (most ____!), and could be
other immunodeficiencies,
3. or if someone has pneumonia, all of these diferent factors can contribute to the development of bronchiectasis
permanent dilation bronchi elastic neoplasm foreign cystic fibrosis immunodeficiency kartagener syndrome virulent staph aureus post-Tb bronchiectasis
bronchioles
alveolar
obstruction
common
Pathogenesis
• Obstruction and Chronic Persistent Infection
____ > impaired clearance of ____ > superimposed ____ > inflammation in bronchial wall > desutrction of muscle/elastic fiber/fibrosis > irreversible dilation
Persistent ____ in the bronchi/bronchiole > inflammation in bronchial wall > destruction of muscle/elastic fiber/fibrosis > irreversible dilation
pathogenesis is obstruction and chronic persistent infection.
-if normal defense mechanism of the lung is compromised, obstruction of that will lead
to chronic infection.
which comes first? can happen either way
LEFT CHART:
If there is obstruction due to ____ in lung, or because there is a lot of ____, there is an impaired cleanse of secretion which leads to superimposed infection.
When there is infection, leads to ____, and eventually that inflammation will be
____ and there will be destruction of muscle and fibrosis. If there is destruction of muscle fiber, will lead to ____ of the bronchiole. Similar to emphysema but location is ____.
RIGHT CHART:
Persistent infection of the bronchi leads to the same thing. Inflammation of the bronchial wall, destruction of the muscle fiber. As the ____ are destroyed, bronchioles are not able to contract and you get ____.
obstruction (lung cancer/foreign body) secretion infection cancer or foreign body mucus superimposed infection acute irreversible dilation different
elastic fibers
bronchitis
Clinical features of Bronciectasis and Treatment
- Clinical:
- Severe Persist ____
- Expectoration of ____
- Episodic: Precipitated by ____ infection
- ____
- Treatment:
- ____
- ____
- ____
- ____ therapy (severe disease)
what are the clinical manifestations?
people with bronciectasis, they have all this mucus and chronic inflammation…
1. they have persistent cough
2. cough out mucus and sputum.
3. they have episodic infection
4. and they have reduced oxygen in blood.
how do you treat them?
- you can treat the infection with antibiotic,
- you can treat the inflammation with corticosteroid,
- you can use bronchodilators because you are fixing narrowing.
- or you can use oxygen therapy these often develop from chronic bronchitis but in some individuals with ____ it occurs because of a diferent reason.
cough
mucopurulent sputum
respiratory
hypoxemia
antibiotics
corticosteroids
bronchodilators
oxygen
cystic fibrosis
Bronchial Asthma
• Chronic Inflammation of airways that causes ____ episodes of wheezing, breathlessness and cough
• Hallmarks: – \_\_\_\_ Airway obstruction – \_\_\_\_ Inflammation (\_\_\_\_) – \_\_\_\_ hypertrophy/Hyper-reactivity – Increased \_\_\_\_
• Bronchial inflammation ○ Eosinophils are involved ○ Bacterial infection - neutrophils; but bronchila asthma > \_\_\_\_, some neutrophils, but eosinophils are ht eprimary players • Hyper-reactive > bronchiol SM is now \_\_\_\_ > contracting more \_\_\_\_ > indiviudla with asthma would have episodes of asthma and cough • Produce \_\_\_\_ antibodies > bind to high affinity receptors on \_\_\_\_ cells, when allergen comes along > mast cells will mediated to give the manifestations of \_\_\_\_ • A lto of people who have asthma > develop in \_\_\_\_
recurrent reversible bronchial eosinophils smooth muscle mucous secretion
eosinophils
larger rigorously IgE mast asthma childhood
Asthma
Early phase (minutes to hours)
- ____ (earliest)
- increased ____, vasodilation, increased ____ begin
Late phase (hours and longer)
- ____ production (epithelial cells)
- recruitment of ____, neutrophils and ____
- inflmmation and further ____
airway obstruction: ____, also edema and ____
• Sensitization phase: exposed to allergen > T cell activation > B cells activated > produce \_\_\_\_ ○ Only arming mast cells with Ig • Next earl yphase: when allergen cross-links Ig on mast cells > \_\_\_\_ > \_\_\_\_ > mast cells produce constrictors; vasodilation, and icnreased vascular permeability • \_\_\_\_ in both atopic and non-atopic ○ Difference > atopic is Ig and non-atopic is \_\_\_\_ ○ How are they activated § Allergic one > \_\_\_\_ cell activation > produce cytokines that produce Ig > \_\_\_\_-cell activated; also produce \_\_\_\_ and \_\_\_\_ > involved in bronchiol \_\_\_\_ § Non-atopic asthma > non-Ig mediated > produced by\_\_\_\_, microbes, smoke > irritants activate the epithelail cels to produce cytokines > \_\_\_\_, \_\_\_\_, \_\_\_\_ > receptors for these on \_\_\_\_ (not a regular lymphocyte, because not expressed on normal receptors) > produce \_\_\_\_, \_\_\_\_ § In the late phases, regardless of whether astham is mediated ebtween atopic and non-atopic, the later airway responseivness > mdiated by \_\_\_\_, and activated by both pathways ○ In non-atopic pathway > no \_\_\_\_ > produced by cells not involved in non-atopic; no \_\_\_\_ involved; but production of IL5 and IL13 > produce allergic and non-allergic eosinophil inflmmation
bronchoconstriction
mucus production
vascular permeability
cytokine
eosinophils
T cells
edema
bronchoconstriction
mucus plugging
IgG degranulation bronchoconstriction eosinophils non-Ig Th2 mast IL5 IL13 hyper-reactivity
glutins IL33 IL25 TSLB innate lymphocyte type 2 IL5 IL13
eosinophils
IL4
B cells
Asthma Classification (Severity, symptoms and lung function tests):
• Intermittent:
– Symptoms occur < ____ days/week
– Does not interfere with ____ activity – FEV1 ≥ ____%
– No ____
• Mild Persistent: – Symptoms occurs on > \_\_\_\_ days/week – Interfere with \_\_\_\_ – Night symptoms \_\_\_\_ times/month – FEV1 ≥ \_\_\_\_% – Low dose \_\_\_\_
• Moderate Persistent: – Symptoms occur each \_\_\_\_ – Severely limits \_\_\_\_ – Frequent night symptoms – FEV1 \_\_\_\_% – \_\_\_\_ ICS+ LABA
• Severe Persistent: – Symptoms occur \_\_\_\_ – Severely limits \_\_\_\_ – Frequent night symptoms – FEV1 symptoms and severity may vary • If someone has intermittent: ○ No \_\_\_\_ of airway (> 80% FEV) • Mild persistent: ○ Same as intermittent ○ Can treat with low doses of inhaled corticosteroid, or leukotriene receptor antagonists • Moderate persistent: ○ FEV1/FVC • Severe persistent: ○ Less than 60%; need high doses now • Some patients are resistant to these treatments
2
normal activity
80
daily medication
2 daily life 3 to 4 80 ICS or LTRA
day
daily activity
60-80
low/medium
each day
daily activity
60
ICS + LABA
obstruction
Asthma drugs:
• \_\_\_\_ • Corticosteriods • \_\_\_\_ • Monoclonal antibodies: – \_\_\_\_ (Zolair; anti-IgE) 2003 – Mepolizumab (Nucala, Anti-IL-5) 2015 – \_\_\_\_ (Cinqair, Anti-IL-5) 2016
• The MaB are expensive • Omali ○ Anti-\_\_\_\_ - binds IgE in circulation, and removes it from circualtion in \_\_\_\_ individuals, and when exposed to allergen again > mast cells don't have ny \_\_\_\_ attached to receptors because the antibody removed them § Doesn't work on every single individual; used to treat people who are over 12 y/o who are resistant to steroid ○ Would expect to work in non-atopic? > NO > no \_\_\_\_, and nothing to remove and owuldn't even try olamizab • Mepo • Reslixu ○ Anti \_\_\_\_ - IL5 important for activating \_\_\_\_ > common denominator for both \_\_\_\_ asthma > works in certain indivudals, but not in a lot of individuals ebcasue of intitial \_\_\_\_ that is mediated by mast cells won't be affected by these MaB ○ Used in combination with other antibodies ○ Very expensive • Newly developed antiobdy against IL13
bronchodilators LT modifiers omalizumab reslixumab IgE atopic IgE IgE IL5 eosinophils atopic and non-atopic bronchoconstriction
Acute Respiratory Distress Syndrome (ARDS)
Definition: Respiratory failure occurring with ____ month of clinical insult with ____
Etiology: ____
Pathogenesis: • \_\_\_\_!!! • \_\_\_\_ • IL-8......\_\_\_\_ recruitment • \_\_\_\_-Neutrophils and Endothelial cells • \_\_\_\_ • Necrosis of \_\_\_\_cells • \_\_\_\_ membrane (next slide)
• Left half of alvoli - norma ○ Alveolar macrophage, and no neutrophils • Right - disease process that happens in ARDS ○ Have \_\_\_\_ ○ The alveolar macrophages when activated they secrete \_\_\_\_, and they secrete \_\_\_\_ (potent chemoattractant for \_\_\_\_) > neutrophils recruited from circulation into the lung ○ Also have edema ○ Neutrophils will release proteases, lipid mediators, and these activated neutrophils will damage the endothelial cells > necrosis of the \_\_\_\_ cell occurs, and also there is a generation of hyaline membrane
1
bilateral opacity
pneumonia/sepsis
neutrophils alveolar macrophages neutrophil IL-1 and TNF edema type I hyaline
neutrophils and alveolar macrophages
TNF
IL8
neutrophils
type I
Acute Respiratory Distress Syndrome (ARDS)
Exudative phase:
• ____, firm, ____, heavy
Microscopy:
• ____ congestion
• Necrosis of ____
• ____ membranes
____ edema + remnants of ____ cells.
How does it look histologically?
- lung is red, velvet, lots of fluid
- this is due to exudate phase of ____ inflammation
- dark red firm, airless, heavy (due to edema that formed. exudate that forms. )
middle picture microscopy: can see neutrophils recruited into lung
-capillary congestions
-alveolar epithelial cells undergo necrosis
-as a result of necrosis get ____ membrane production (fibrin rich edema with
remnants of epithelial cells).
what happens with time? the ____ phase.
dark red airless capillary alveolar epithelial cells hyaline
fibrin-rich
necrotic epithelial
hyaline
healing
Acute Respiratory Distress Syndrome (ARDS)
Healing:
• ____ weeks after lung injury
• Resorption of ____ membranes
• Hypertrophy and hyperplasia of ____ pneumocytes (arrow); Regeneration
• Survivors: Normal respiratory function within ~____ months
• Rest: Diffuse interstitial fibrosis/chronic respiratory insufficiency
With time, we have healing
HEALING:
1. first thing that happens is the hyaline membrane is absorbed.
2. lung epithelial cells try to regenerate and get hypertrophy and hyperplasia of type
2 pneumocystis.
3. if you survive, normal respiratory function is restored within 6 months
4. if you dont:
A. Get difuse interstitial fibrosis which leads to ____.
B. outcome could be survival and complete lung regeneration
C. BUT if you die, lung undergoes fibrosis occurring at ____ (NOT at
level of bronchioles).
in emphysema, it was lung alveoli that were destroyed.
here it is ____. as a result of shrinkage, FVC is ____
there is no efect on bronchioles, and therefore ratio remains ____
1-2 hyaline type II 6 chronic respiratory insufficiency lung interstitial fibrosis reduced high
Clinical features and Treatment
• Clinical Features: • Life threatening \_\_\_\_ • Histology: \_\_\_\_ – Compromises respiratory function • Severe \_\_\_\_ • Multi-organ failure • ~\_\_\_\_% within 72 h after injury. • Mortality rate ~\_\_\_\_% • \_\_\_\_ prognosis: • Advanced \_\_\_\_ • Multi-system failure
- Treatment:
- Minimize the cause
- ____
- ____ stem cell transplantation?
respiratory insufficiency diffuse alveolar damage (DAD) arterial hypoxemia 85 60 poor age
artificial ventilation
bone marrow
Idiopathic Pulmonary Fibrosis (IPF) • \_\_\_\_, progressive, \_\_\_\_ interstitial fibrosis • Severe \_\_\_\_ and cyanosis • \_\_\_\_ >females; >\_\_\_\_ years • Unusual i\_\_\_\_
* Don't know the \_\_\_\_ * Pulmonary/lung fibrosis * \_\_\_\_ activated > bring in neutrophils > produce factors that activate \_\_\_\_ > produce proteases > damage to \_\_\_\_ pneuomocyte > hypertrophy and hyperplasia of \_\_\_\_ > bring back to normal, also secrete fibrogenic and chemotactic factors that bring in fibrobblasts; macrophages releaseing \_\_\_\_ * End result: activation of fibroblasts > produce \_\_\_\_, and produce \_\_\_\_
patchy bilateral hypoxemia males 60 interstitial pneumonia
etiology macrophages fibroblasts type I type II TGFb collagen fibrosis
Idiopathic Pulmonary Fibrosis (IPF)
• ____ appearance
• Fibrosis more pronounced in ____ region
• Unusual interstitial pneumonia (UIP)
with time, moves more centrally.
outline is sub pleural region. you can see fibrosis here. whereas more centrally, lung
parenchyma is more ____.
the further you move towards subpleural region, the higher the deposition of ____
is.
cobblestone
subpleural
intact
collagen
Clinical features of IPF and Treatment
Clinical Features: • \_\_\_\_ onset, \_\_\_\_ cough • \_\_\_\_ • \_\_\_\_, Cor pumonale • \_\_\_\_ findings often diagnostic • \_\_\_\_ biopsy in some cases
• Cobblestone appearance is \_\_\_\_ • Surgical biopsy > will see \_\_\_\_ (also diagnostic) • Treatment: ○ When lung undergoes fibrosis, little you can do ○ Lung transplantation > and if isn't done > mean survival is 3 years § Because of \_\_\_\_ and \_\_\_\_
gradual non-productive progressive dyspnea cyanosis clinical and radiologic surgical
diagnostic
UIP
respiratory failure
RSHF
Pneumoconiosis
- Pneumon (lung) konis (dust) = Dusty lung
- ____ reaction to inhaled dust
- Coal dust, ____ and Asbestos
- Particles ____ μm in diameter• If particles are big, will remove thorugh ____ of ____ ariwasy, but if small > get to the ____ part of lung > activate ____
non-neoplastic silica 1-5 normal defense upper lower macrophages
Silicosis:
•The most prevalent ____ occupational disease in the world
•~2.0 million construction workers in the US are exposed to respirable crystalline silica
•~300,000; brick manufacturing
- top left pic:
A. macrophage trying to ingest silica particle, releases ____ which brings in fibroblasts, fibroblasts are produced which secrete ____, and through cytokines released from the alveolar macrophages, get ____, - bottom left pic:
A. a whirl of collagen mixed with ____ and ____• Fibrosis
• R: normal alveoli on the ____
○ Many alveoli in the red
○ Because of the reaction, many of alveoli have undergone ____ > coalesce together and give ____ tissue in lung
chronic
cytokines
collagen
lymphocytic division
macrophages
lymphocytes
edges
fibrosis
nodular fibrotic
Clinical features and Treatment
Clinical: - usually detected in chest radiograph in \_\_\_\_ workers • Nodules in \_\_\_\_ of lung • \_\_\_\_ after *PMF is present • Death due to: – \_\_\_\_ – \_\_\_\_ – \_\_\_\_ • *Progressive massive fibrosis
- Treatment:
- ____
- *OSHA ruling (2015)
- Reduce silica exposure to ____ ug/m3 of air averaged over an ____ hour shift
- Prevent 900 new cases/year
- Save 600 lives
- Net benefit ~$7.7b/year
- *Occupational Safety Health Administration• Indiviudals are not aware they’re developnig this disease
○ Asymptomatic > detected inc hest radiograph; takes a while of rnodules to develop in lung
• Nodules present in upper part of lung
• If have fibrosis (smaller) > breathe normally
• Treatment
○ Nothing you can do to treat after diagnoised > the lung is udnergoing fibrosis
asymptomatic upper zones shortness of breath hypoxia pulmonary hypertension cor-pulmonale
none
50
8
• ARDS ○ Lung looks \_\_\_\_ ○ Initial phase, \_\_\_\_ membrane that will be resolved • IPF ○ \_\_\_\_ - can diagonise ○ \_\_\_\_ - diagnose • Pneumo ○ Both PF and this have \_\_\_\_, but the histology is different
inflated and red hyaline radiograph histology fibrosis
Emphysema Site: \_\_\_\_ Etiology: \_\_\_\_ Pathologic changes: \_\_\_\_ Sign/Symptom: \_\_\_\_
Chronic bronchitis Site: \_\_\_\_ Etiology: \_\_\_\_ Pathologic changes: \_\_\_\_ Sign/Symptom: \_\_\_\_
Asthma Site: \_\_\_\_ Etiology: \_\_\_\_ Pathologic changes: \_\_\_\_ Sign/Symptom: \_\_\_\_
Bronchiectasis Site: \_\_\_\_ Etiology: \_\_\_\_ Pathologic changes: \_\_\_\_ Sign/Symptom: \_\_\_\_
acinus
tobacco
alveoli wall destruction
dyspnea
bronchus
tobacco/air pol
hyper-secretion
cough, sputum
bronchus
immunlogic other
SM, mucus, inflamm
wheezing, cough, dyspnea
bronchus
persistent infection
dilation and scarring
cough, sputum, fever
ATELECTASIS:
• Collapse/Loss of lung volume • ____
• ____
• Collapse of expanded Lung
– Compromises ____
– ____
– ____
• \_\_\_\_ lungs can collapse
restrictive obstructive oxygenation hypoxia infection one or both
Atelectasis (airless lung)
diferent names for atelactisis: contraction, compression, and resoption.
CONTRACTION:
1. if lung is undergoing ____, volume of lung is ____ and lung ____.
COMPRESSION:
1. lung parenchyma is normal, there is no ____
2. one can think about air getting into lung
A. if involved in ____, can burst a lung, air bursts out and compresses lung
B. if blood gets into the lung (____ diseases)
C. hydrothorax: one example is ____, fluid can compress lung
3. When lung volume is reduced due to (reads box)
RESORPTION:
1. if there is a blockade in one or more of ____
2. can result from (reads bullets)
3. can all block air getting into lung. air is not getting into lung. any air that is gets
resorbed into other parts of ____ and lung ____
all are reversible EXCEPT ____ bc lung has undergone ____ damage. has been replaced by fibrotic tissue
fibrosis
reduced
collapses
fibrosis
car accident
blood
CHF
bronchioles
body
collapses
contraction
irreversible
Causants
Compression
- ____
•Hemothorax (Blood)
•____ (Trasudate, ____) •Empyema (Exudate)
Contraction
• ____
•Irreversible
Resorption •\_\_\_\_ •Foreign body •\_\_\_\_ during oral surgery •Bronchial Asthma •\_\_\_\_ •Bronchiectasis •\_\_\_\_
pneumothorax hydrothroax CH fibrosis tumor blood clot chronic bronchitis mucus/mucopurulent plug
