Respiratory System Pathology 2 - Galbraith lecture Flashcards Preview

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1

Characteristics of Obstructive Lung diseases

Increased resistance to airflow due to partial or complete obstruction from level of trachea to larger bronchi to terminal and respiratory bronchioles

decreased maximal flow rates during forced expiration (FEV1/FVC less than 0.7)

2

Obstructive lung diseases

Emphysema
Chronic bronchitis
Asthma
Bronchiectasis
COPD

3

COPD incidence

Women, african americans

Smoking
environmental/occupational pollutants

4

Emphysema

destruction of airway walls and irreversible enlargement of airways distal to the terminal bronchiole

Classification based on site of involvement within pulmonary acinus
-Centriacinar
-Panacinar
-Distal acinar
-Irregular

5

Centriacinar emphysema

heavy smokers
often with COPD

respiratory bronchioles involved, spares distal alveoli

upper lobes/apical segments

6

Panacinar emphysema

a1-antitrypsin deficiency

alveoli distal to respiratory bronchioles involved

lower and anterior aspects of lungs (bases most severely involved)

7

Emphysema pathogenesis

Exposure to injurious particles in tobacco smoke stimulates inflammation
-IL8, TNF recruit inflammatory cells

Imbalance of proteases and antiproteases
-inflammatory cells release elastase

Oxidative stress
-smoke, inflammatory cell oxidants, continuing cycle of tissue damage and inflammation

8

Pathways of smoking and genetic predisposition leads to alveolar wall destruction

-oxidative stress, increased apoptosis and senescence

- inflammatory cells, release of inflammatory mediators

-protease-antiprotease imbalance
*complicated by congenital a1-antitrypsin deficiency

9

a1-antitrypsin deficiency

a1-antitrypsin potent antiprotease

Pi locus on Ch14

Homozygotes for Z allele have significant decrease in a1-antitrypsin

80% PiZZ develop symptomatic panacinar emphysema, accelerated and more severe if pt smokes

Cirrhosis, emphysema risk

10

Emphysema as an obstructive lung disease

small airways normally open by elastic recoil of lung parenchyma

Destruction of elastic alveolar walls surrounding respiratory bronchioles --> collapse of bronchioles during expiration

11

Clinical course of emphysema

No symptoms until 1/3 of lung tissue is affected

Initial symptoms: dyspnea, cough, wheezing

Lean forward, and breath out with pearced lips

Severe: weight loss, barrel chest - overdistension, prolonged expiration, "pink puffer" due to over ventilation

May progress to pulmonary HTN and right sided failure

12

Death causes in emphysema

CAD
Respiratory failure
RHF
Pneumothorax --> lung collapse

13

Chronic bronchitis

Chronic, persistent productive cough without other identifiable cause

smokers, inhabitants of polluted environments

14

Pathogenesis of chronic bronchitis

Initiating factor: exposure of bronchi to inhaled irritants

mucus hyper secretion

Chronic inflammation --> damage and fibrosis of small airways

Diminished ciliary action of respiratory epithelium, leading do stasis of mucus

15

Morphology of chronic bronchitis

edema and swelling of respiratory mucosa with squamous metaplasia

Hyperplasia of submucosal mucous glands of trachea and larger bronchi
-thickness of mucus gland layer increases

Increased goblet cells in small bronchi and bronchioles and extensive small airway mucous plugging

16

Clinical course of chronic bronchitis

Persistent productive cough

dyspnea on exertion

Hypercapnia, hypoxia, mild cyanosis ("blue bloater")

17

Asthma

Chronic disorder of conducting airways
-recurrent bronchoconstriction
-inflammation of bronchial walls
-increased mucus secretion

Symptoms:
-recurrent wheezing, SOB, chest tightness, cough
-more frequent at night/early morning

18

Atopic asthma

Type I - IgE mediated hypersensitivity reaction

Onset in childhood

high serum IgE, positive skin test for inciting allergen, or IgE Abs to specific allergens

FHx of asthma

19

Atopic asthma pathogenesis

Th2 sensitization to allergen stimulates IgE production of IL4, IL 13 recruiting eosinophils (IL5), stimulates mucus production (IL13)

IgE binds to Fc receptors on mast cells
-reexposure cross links IgE on mast cells --> degranuation and immediate hypersensitivity reaction

20

Immediate phase of atopic asthma hypersensitivity reaction

Minutes

bronchoconstriction
mucous secretion
Increased vascular permeability

21

Late phase of atopic asthma hypersensitivity reaction

recruitment of more inflammatory cells (neutrophils, eosinophils, lymphocytes)
--> damage to mucosal tissue

22

Non-atopic asthma

Bronchoconstriction triggered by varied stimuli:
-respiratory viruses
-inhalation of irritants (smoke)
-cold air
-exercise

23

Morphology of asthma

Repeated allergen exposure and reaction induces "airway remodeling"
-Bronchial wall sm. m. hypertrophy and hyperplasia
-Subepithelial fibrosis
-Submucosal gland hyperplasia, increased goblet cells
-increased airway vascularity
-increased thickness of airway wall

Severe cases: bronchi and bronchioles occluded by thick mucus plugs
-expelled in sputum or BAL specimens (Curshmann spirals)
-contain numerous eosinophils and Charcot-Leyden crystals (atopic cases)

24

Clinical course of asthma

Acute asthma attack may last hours, lower baseline level constantly

Severe acute asthma - status asthmaticus - attack lasts for days, result in obstruction sufficient to cause death

25

Bronchiectasis

Chronic recurrent necrotizing infections destroy smooth muscle and elastic tissue --> permanent dilation of bronchi and bronchioles

Infection with assoc. inflammation and destruction may follow obstruction and impedance of normal drainage

severe bronchial infections may cause enough inflammatory damage and necrosis to bring about bronchiectatic changes

26

Predisposing conditions for bronchiectasis

conditions affecting mucus clearing:
- primary ciliary dyskinesia
-cystic fibrosis
-other bronchial obstruction

immunodeficiency conditions

27

Peribronchial fibrosis

result of repeated attempts to resolve inflammatory process

may be extensive enough to obliterate nearby bronchioles
-bronchiolitis obliterans

28

Cystic fibrosis genetic cause

abnormal function or lack of epithelial Cl- channel - cystic fibrosis transmembrane conductance regulator

CFTR gene on Ch7

29

CTFR

Transports Cl-
-in sweat glands, from the surface into the cell
-other epithelia from cell to lumen

Normally inhibits ENaC - found on epithelial cell apical surfaces, except in sweat glands

Lack of functioning CTFR --> overactive ENaC, resulting in epithelia taking up sodium ions and water passively following

30

Cystic fibrosis

Deficient hydration of airway mucus leads to defective ciliary activity

leads to inability to clear mucus and any pathogenic microbes

Chronic infection ensues --> eventual bronchiectasis

31

Infections common in CF

S. aureus
H. influenzae
Burkholderia cepacia

Pseudomonas aeruginosa
-produce mucoid capsule (alginate) which allows it to form a protective biofilm