Pathome - COPD

Question 1

What are the 4 chronic obstructive pulmonary diseases?

Answer 1

Chronic bronchitis

Emphysema

Asthma

Bronchiectasis

Question 2

What is the classic lung volume finding in COPD

Answer 2

FEV1/FVC < 80%

Both are decreased, but FEV1 is decreased more

Question 3

Describe the basic premise behind COPD

Answer 3

Due to obstruction of airflow

Air trapping in the lungs

Question 4

What is the diagnostic definition of chronic bronchitis

Answer 4

Chronic productive cough lasting at least 3 months over a minimum of 2 consecutive years

Question 5

Describe the pathophysiology behind chronic bronchitis

Answer 5

Hypertrophy of bronchial mucinous glands

Reid index (thickness of mucosal gland layer relative to bronchial wall thickness) >50%

Question 6

Does chronic bronchitis cause “pink puffers” or “blue bloaters” and why?

Answer 6

Blue bloater

Mucus plugs trap CO2

Question 7

How can COPD lead to cor pulmonale?

Answer 7

When there is lack of O2 to majority of the lung, all those blood vessel will constrict, leading to pressure backing up to R heart, leading to R heart failure

Question 8

Describe the pathophysiology behind emphysema

Answer 8

Destruction of alveolar air sacs due to (1) loss of elastic recoil and (2) collapse of airways

Leads to physiologic obstruction and air trapping

Think of a large grocery bacg instead of multiple small balloons

Question 9

What is the cause of destruction of alveolar air sacs in emphysema

Answer 9

Imbalance of proteases (destroy pathogens that make it to small airways e.g. elastase) and anti-proteases

(1) Inflammation = increased proteases (e.g. smoking)
(2) Decreased anti-proteases = a1-anti-trypsin deficiency (A1AT is what neutralizes elastase)

Question 10

What type of emphysema will you see in smoking vs. A1AT deficiency

Answer 10

Smoking: centri-acinar emphysema more in upper lobes

A1ATD: pan-acinar emphysema more in lower lobes

Question 12

What other organ does A1ATD affect and why?

Answer 12

Liver cirrhosis

Liver is still making A1AT, but mutation causes it to be misfolded, so protein accumulates in hepatocytes

Question 13

What part of the hepatocyte does misfolded A1AT accumulate in and what does biopsy reveal

Answer 13

Endoplasmic reticulum

Biopsy shows PAS-positive globules in hepatocytes

Question 14

What are the normal/abnormal alleles in A1ATD

Answer 14

PiM is normal; PiZ is abnormal

PiMZ heterozygotes are usually asymptomatic but have significant risk of emphysema with smoking

PiZZ homozygotes are at significant risk for panacinar emphysema and cirrhosis

Question 15

Does emphysema cause “blue bloaters” or “pink puffers” and why?

Answer 15

Pink puffers

Patients are able to prevent airway collapse by pursing lips and exhaling slowly in order to create back-pressure

Question 16

What is a common gross/x-ray appearance in emphysema

Answer 16

Barrel-shaped chest

Question 17

Describe the basic premise of asthma

Answer 17

Reversible airway bronchoconstriction, usually due to allergic stimuli

Question 18

Describe the pathogenesis of type I hypersensitivity in asthma

Answer 18

Allergens induce Th2 cells

Th2 cells secrete IL-4 (IgE class switching), IL-5 (eosinophils), and IL-10 (increased Th2 and inhibiton of Th1)

Reexposure to allergen leads to IgE-mediated activation of mast cells

Mast cells release:

(1) Histamine (vasodilaiton and increased permeability)
(2) Leukotrienes (bronchoconstriction)

Question 19

Describe 2 histologic findings in asthma

Answer 19

(1) Curschmann spirals (shed epithelium forms wholed mucus plug)
(2) Charcot-Leyden crystal (eosinophil-dervied needle-like crystals) - see next slide for image

Question 20

Charcot-Leyden crystals

Answer 20

eosinophil-dervied needle-like crystals

Question 21

Describe the basic premise of bronchiectasis

Answer 21

Permanent dilation of bronchioles and bronchi

Dilation leads to turbulent airflow instead of accelerated, straight line flow –> air trapping

Question 22

What are the causes of bronchiectasis

Answer 22

Necrotizing inflammation with damage to airway walls:

• Cystic fibrosis
• Kartagener sydrome
• Tumor or foreign body
• Necrotizing infection
• Allergic bronchopulmonary aspergillosis

Question 23

What is Kartagener syndrome?

Answer 23

Defect in the dynein arm of cilia

Leads to sinusitis, infertility, situs inversus, bronchiectasis