L3- Pulmonary Pathology II Flashcards
ALI = (1- include alternate name) is characterized by (slow/rapid) onset of (3) and (4) in the absence of (5).
1- acute lung injury // noncardiogenic pulmonary edema 2- abrupt / rapid onset 3- significant hypoxemia 4- bilateral pulmonary infiltrates 5- cardiac failure
(1) is the histological manifestation of ALI/(2)/(3). (1) is the root cause of (4).
1- DAD, diffuse alveolar damage
2/3- (acute lung injury), noncardiogenic pulmonary edema, shock lung syndrome
4- ARDS (acute respiratory distress syndrome)
DAD is the main cause of (1) during one of the following settings: (2). (1) is characterized by (3).
(diffuse alveolar damage)
1- ARDS, acute respiratory distress syndrome
2- sepsis, severe trauma, diffuse pulmonary infection (etc)
3- progressive respiratory insufficiency
list the ‘direct’ causes of pulmonary insult in ARDS (hint- 6)
- pneumonia
- aspiration
- emboli
- inhalation injury
- drowning
- oxygen toxicity
list the ‘indirect’ causes of pulmonary insult in ARDS (hint- 7)
- sepsis
- trauma with shock
- acute pancreatitis
- severe burns
- blood transfusion (or its products)
- uremia
- drugs
list the risk factors for ARDS
Non-heritable: smoking and alcohol
Heritable: several genes, includes variants that map genes linked to inflammation and coagulation
list the steps of ARDS/ALI pathogenesis
1) endothelial activation
2) adhesion and extravasation of neutrophils
3) accumulation of intra-alveolar fluid and formation of hyaline membranes
In ARDS/ALI, endothelial activation occurs in response to….
(1st of 3 steps of pathogenesis)
- directly by circulation inflammatory factors
- secondary to pneumocyte injury
- *mediated by alveolar macrophages
In ARDS/ALI, after endothelial activation, (1) is increased on the endothelium in order to (2) and migrate them into (3). Once (2) enters into (3), (4) will occur.
(2nd of 3 steps of pathogenesis) 1- adhesion molecules 2- bind neutrophils 3- interstium and alveoli 4- degranulate and release inflammatory mediators
In ARDS/ALI, inflammatory molecules from neutrophils leads to (1) within the alveoli. (1) will lead to the loss of (2) and the deficiency of (3). As a result (4) and (5) accumulate within the alveoli in order to form (6).
(3rd of 3 step of pathogenesis) 1- leaky capillaries 2- diffusion across alveolar membrane 3- surfactant (type II pneumocyte damage) 4- protein rich fluid 5- cellular debris 6- hyaline membrane
list the chemical mediators involved in the pathogenesis of ARDS/ALI
CKs oxidants GFs TNF IL-1, IL-6, IL-10 TGF-β
In the resolution of ARDS/ALI, (1) enter the intra-alveolar space in order to remove debris and (2) leading to (3). (4) will proliferated to replace pneumocytes. Endothelium will restore as a result of (5).
1- macrophages 2- release fibrogenic factors 3- fibrosis of alveolar wall 4- bronchiolar stem cells 5- proliferation of uninjured capillary endothelium
list the phases exhibited histologically for ARDS
(DDD- diffuse alveolar damage)
1) acute / exudative phase, 0-4 days
2) organizing / proliferative phase, 4 days - 3 wks
Acute phase, aka (1), occurs for (2) duration after onset of ARDS. It is characterized by a (3) gross appearance of the lungs, (4) of the interstitium and intra-alveolar spaces, and (5) of the alveolar epithelium in order to create (6), the main characteristic feature.
1- exudative phase 2- (days 0-4) 3- heavy, firm lungs 4- edema / hemorrhage 5- necrosis and sloughing of cells 6- Hyaline Membranes
Organizing phase, aka (1), occurs for (2) duration after onset of ARDS. It starts with the proliferation of (3) and the organizing of (4) in order to establish (5) as the end result.
1- proliferative phase 2- (day 4 - week 3) 3- type II pneumocytes 4- fibrin exudates into Fibrosis 5- alveolar septal thickening
(Note- there is resorption of the Hyaline Membranes created in the acute phase)
list the sign and symptom progression of ARDS/DAD
- rapid onset, w/in wks
- severe dyspnea –> tachypnea –> hypoxemia (refractory to O2 therapy)
- cyanosis
- respiratory failure
how is ARDS/DAD investigated
1) diffuse bilateral infiltrates on radiograph (i.e. CXR)
2) V/Q mismatch (ventilation perfusion mismatch)
ARDS/DAD has a (1) mortality rate, where (2) are factors that indicate a poor prognosis. If there is recovery, normal function may take up to (3- time) to return. It is treat with (4).
1- 40% (although decreasing)
2- advanced age, bacteremia/sepsis, progression to multi-system organ failure
3- 6-12 mos
4- supportive therapy
Obstructive lung diseases are considered (1) disorders and affect the (2) parts of the lung. (3) is increased and is exhibited by (4) on spirometry.
1- airway disorders
2- trachea to terminal bronchioles
3- airflow resistance (limits expiratory rates on forced expiration)
4- reduced FEV1/FVC ratio
Restrictive lung diseases are considered (1) disorders and affect the (2) parts of the lung. (3) are decreased and is exhibited by (4) on spirometry.
1- parenchymal disorder
2- respiratory bronchioles to alveoli / alveolar ducts
3- TLC, O2 diffusing capacity, other lung volumes, lung compliance
4- inc FEV1/FVC ratio (or normal)
Obstructive lung disease spirometry, indicate inc, dec, or no change to the following:
TLC, FEV1, FVC, FEV1/FVC, FRC, RV
TLC- inc FEV1- large dec FVC- dec FEV1/FVC- dec, <0.7 FRC- inc RV- inc
Restrictive lung disease spirometry, indicate inc, dec, or no change to the following:
TLC, FEV1, FVC, FEV1/FVC, FRC, RV
TLC- dec FEV1- dec FVC- large dec FEV1/FVC- inc/normal. >0.8 FRC- dec RV- dec
list the common obstructive lung diseases (hint- 4)
emphysema
chronic bronchitis
asthma
bronchiectasis
list the common restrictive lung diseases (hint- 4)
- Acute Restrictive Disease: ARDS
- Chronic Restrictive Disease: interstitial fibrosis, pneumoconiosis, granulomatous
- chest wall deformities
- neuromuscular
COPD affects (men/women) more
affects men and women equally
compare COPD to Asthma in terms of types of airflow obstruction
COPD (+ emphysema, bronchiectasis): loss of elastic recoil –> expiratory obstruction secondary to airway collapse // Irreversible
Asthema: anatomic airway narrowing // Reversible
list the 3 reasons why chronic bronchitis and emphysema are grouped together in COPD
1) smoking is common trigger
2) overlapping features: many Pts present with features of both conditions
3) management of disease is similar
Emphysema is characterized by (1) occurring in the (2) part of the lung. It is accompanied by (3), but (4) is importantly absent.
1- abnormal permanent airspace enlargement
2- distal to terminal bronchioles
3- destruction of airspace walls
4- fibrosis
list the 4 types of Emphysema
- Centrilobular / Centriacinar
- Panlobular / Pananinar
- Para-septal / Distal Acinar
- Irregular / Paracicatricial
In centrilobular, aka (1), emphysema, the (2) parts of the respiratory tract is affected and the (3) part of the lung is most affected. (4) is the common cause. (5) is a unique feature seen in individual lobules.
1- centriacinar
2- respiratory bronchiole (spares distal alveoli)
3- upper lungs
4- smoking
5- diseased and normal airspaces in same lobule
the most common emphysema is (1); (2) is the other common emphysema seen in practice
1- centrilobular / centriacinar
2- panlobular / panacinar
In panlobular, aka (1), emphysema, the (2) parts of the respiratory tract is affected and the (3) part of the lung is most affected. (4) is the common cause.
1- panacinar
2- respiratory bronchiole to distal alveoli affected
3- lower lung
4- AAT-1 deficiency
describe the 2 rare or less common emphysemas
Para-septal / Distal acinar:
- next to atelectasis, along septa, margins of lobes, subpleural
- more common in upper lobes
- bullae may form
- may lead to pneumothorax
Irregular / Paracicatrical: surrounding scar, asymptomatic
Emphysema pathogenesis is based on (1). The (2) component of one is released from (3) after its infiltration, and functions to (4). The (5) factor plays a protective role in the lung. Therefore an increase in (2) or decrease in (5) can lead to (6).
1- imbalance of protease-antiprotease mechanism
2- protease
3- neutrophils (+ other leukocytes)
4- destroy lung tissue
5- antiprotease (ex. AAT, inhibits neutrophilic proteasses)
6- destruction of alveolar parenchyma
what are the 3 genetic factors that play a role in emphysema
A1AT deficiency: antiprotease deficiency, accompanied by abnormal protein accumulating in liver => chronic liver disease
TGF-β gene polymorphism: dec signaling => inadequate elastin repair
MMP gene polymorphisms: inc in emphysema
A1AT is a (1) type protein. Its abnormal form from (2) genotype found on chromosome (3), can have abnormal folding, leading to accumulation in (4) causing (5).
1- antiprotease (in lung) 2- Pi-ZZ (Pi-MM is normal) 3- chr.14 4- liver 5- chronic liver disease
list the 3 major histological features of emphysema
- large alveolar spaces
- alveolar septa destruction w/o fibrosis (septa is free flowing in air spaces)
- elastin destruction in small airways => lung collapse during expiration, a functional obstruction
describe the symptoms or patient presentation for emphysema
- dyspnea, insidious/progressive onset
- productive cough, variable
- weight loss, hyperventilation and excessive puffing/panting => pink puffers
describe the signs seen on patient exam for emphysema
- barrel chest
- prolonged expiration + pursed lips
- sitting forward, hunched trying to squeeze air out of lungs
describe the spirometry results for emphysema
- inc lung volumes: TLC, RV
- dec FVC, FEV1 (more so) => FEV1:FVC dec
- dec DLCO (diffusing capacity for the lungs) due to loss of SA in lung for diffusion
describe the results of CXR and blood gases seen in emphysema
CXR: inc air trapping, flat domes of diaphragm
Blood Gases: normal until later presentation (pink puffers), showing hypoxia, hypercapnia, respiratory acidosis
The main end progression of emphysema is (1), and (2) is the main complication seen.
1- irreversible lung damage
2- Cor Pulmonale
describe how to diagnose chronic bronchitis
(clinical Dx) persistent productive cough: ->3 consecutive mos in a yr ->2 consecutive yrs -no other identifiable cause
Chronic bronchitis is mostly caused by……
inhaled irritants: smoking or urban dweller inhalation of SO2, NO2
describe the steps of pathogenesis for chronic bronchitis in response to inhaled irritants
1) submucosal gland hypertrophy => mucus hypersecretion
2) goblet cell metaplasia in bronchioles
3) smooth muscle hyperplasia + peribronchiolar fibrosis => small airway obstruction distally
4) inflammation: Tc cells, macrophages, neutrophils
describe the gross appearance of the lung in chronic bronchitis
- hyperemia and edema of mucous membranes
- excessive mucinous or mucopurulent secretions
describe the histological appearance of the lung in chronic bronchitis
- inc Reid index = thick mucus gland layer
- goblet cell metaplasia
- smooth cell hyperplasia
- peribronchiolar fibrosis
- irritant => squamous metaplasia
describe Reid index and its relationship to chronic bronchitis
Reid Index- ratio of thickness of mucous gland layer to thickness of wall between epithelium and cartilage
-chronic bronchitis, >40%
describe the symptoms or patient presentation for chronic bronchitis
- persistent cough (see criteria in other slide)
- progression to dypsnea upon exertion
- cyanosis (blue bloaters)
describe the signs seen on patient exam for chronic bronchitis
- hypoxia, hypercapnea, cyanosis
- persistent hypercapnea –> desensitizes PCO2 sensitive centers –> switch to respiration drive based on PO2 –> caution needed with O2 therapy
what are the 2 main complications that stem from chronic bronchitis
- secondary infections
- pulmonary HTN –> Cor Pulmonale
compare i) age of onset and ii) CXR results between emphysema and chronic bronchitis
i) age of onset
Emphy: 50-75 y/o
CB: 40-45 y/o
ii) CXR
Emphy: hyperinflation, small heart
CB: prominent vessels, large heart
compare i) airway resistance and ii) elastic recoil between emphysema and chronic bronchitis
i) airway resistance:
- Emphy: normal or slight inc
- CB: inc
ii) elastic recoil:
i) Emphy: low
ii) CB: normal
compare presentation of i) dyspnea, ii) cough, and iii) general appearance between emphysema and chronic bronchitis
Emphysema:
i) severe and early dyspnea
ii) late, scanty sputum in cough
iii) pink puffer
CB:
i) mild and late dyspnea
ii) early, copious sputum in cough
iii) blue bloater
compare presentation of i) infections, ii) respiratory failure, and iii) cor pulmonale between emphysema and chronic bronchitis
Emphysema:
i) occasional
ii) terminal
iii) rare, terminal
CB:
i) common
ii) repeated (cyclic)
iii) common
