respiratory system path Flashcards
refers to an area or areas of airless pulmonary parenchyma, due to collapse or incomplete expansion
atelectasis
◦ Complete obstruction of an airway
◦ Air within the dependent lung is resorbed→ collapse
◦ Mediastinum shifts toward the affected lung
resorption atelectasis
in resorption atelectasis, mediastinum shifts ____the affected lung
toward
◦ Fluid, tumor or air accumulate within the
pleural space, preventing normal
expansion
◦ Mediastinum shifts away from the
affected lung
compression atelectasis
in compression atelectasis, mediastinum shifts ____from affected lung
away
◦ Pulmonary or pleural fibrosis preventing
normal expansion
◦Not reversible
contraction atelectasis
two types of pulmonary edema
- hemodynamic pulmonary edema
- edema secondary to microvascular (alveolar injury)
◦ Intra-alveolar fluid accumulation due to increased hydrostatic pressure
in the pulmonary circulation (fluid forced out of them)
◦ Hemosiderin-laden macrophages may be seen within alveoli (“heart
failure cells”) with chronic pulmonary edema
◦ ↓oxygenation, ↑ chance of infection
Hemodynamic pulmonary edema
(heart failure)
◦ Injury to and inflammation of alveolar vascular endothelium and/or
respiratory epithelium
◦ Infectious or toxic insults
◦ May be localized or diffuse
Edema secondary to microvascular (alveolar) injury
Characterized by an increase in resistance to airflow due to
partial or complete obstruction at any level from the
trachea and larger bronchi to the terminal and respiratory
bronchioles
obstructive lung diseases
demonstrated with pulmonary function testing,
which will show decreased maximal flow rates during forced
expiration
obstructive lung diseases
obstructive lung diseases:
1
2
3
4
- emphysema
- chronic bronchitits
- asthma
- bronchiectasis
(COPD are 1 and 2 together)
in COPD, who are most susceptible to COPD than other groups
women and african americans
COPD has a strong association with:
smoking
35-50% of heavy smokers develop COPD
80% of COPD is due to smokinh
other risks: environment/occupational pollution
Destruction of airway walls and irreversible enlargement of
the airways distal to the terminal bronchiole
emphysema
emphysema is classified based upon the site of involvement within a pulmonary acinus:
- centriacinar
- panacinar
- distal acinar
- irregular
- Occurs predominantly in heavy smokers, often along with chronic bronchitis (COPD)
- respiratory bronchioles are involved, sparing the distal alveoli
- more lesions seen in upper lobes/apical segments
centriacinar emphysema
- Associated with α1
-antitrypsin deficiency - Alveoli distal to the respiratory bronchioles are involved
- occurs more frequently in the lower and anterior aspects of
the lungs (lung bases are most severely involved)
panacinar emphysema
emphysema pathogenesis
- Exposure to injurious particles in tobacco smoke stimulates
inflammation - imbalance of proteases and antiproteases
- oxidative stress
emphysema pathogenesis
what is
Lung epithelial cells and macrophages release chemotactic factors
(IL-8, TNF, etc) to recruit inflammatory cells from the circulation
Exposure to injurious particles in tobacco smoke stimulates
inflammation
emphysema pathogenesis
what is
Inflammatory cells release destructive proteases (elastase)
imbalance of proteases and antiproteases
emphysema pathogenesis
what is
Smoke, inflammatory cell products contain oxidants, continuing
the cycle of tissue damage and inflammation
oxidative stress
potent antiprotease, encoded by the Pi
locus on chromosome 14
a1 antitrypsin deficiency
Homozygotes for the ___ allele (0.012% of population) have significant decrease in a1 antitrypsin
Z allele
of homozygotes (PiZZ) will develop symptomatic
panacinar emphysema, accelerated and more severe if the
patient smokes
80%
How is emphysema an obstructive lung
disease?
-small airways are normally held open by the elastic recoil of lung parenchyma
-destruction of elastic alveolar walls surrounding respiratory bronchioles leads to the collapse of those bronchioles during expiration
[can breathe air in, but not out]
emphysema doesnt show symptoms until
1/3 of lung tissue affected
emphysema symptoms
dyspnea
cough
wheezing
with severe:
◦ weight loss
◦ Barrel chest -overdistension
◦ Prolonged expiration
Emphysema may progress to pulmonary ____ and_____
pulmonary hypertension and right-sided heart failure (RHF)
death in emphysma
respiratory failure
RHF
pneumothorax-> lung collapse
chronic, persistent productive cough without any other
identifiable cause
common in smokers
chronic bronchitis
pathogenesis of this includes:
- initiating factor is exposure of bronchi to inhaled irritants
- mucus hypersecretion
- chronic inflammation -> damage and fibrosis of small airways
- diminished ciliary action of respiratory epithelium, leading to stasis of mucus
chronic bronchitis pathogenesis
- Edema and swelling of the respiratory mucosa, often with
squamous metaplasia - hyperplasia of submucosal glands of the trachea and larger bronchi (thickness of mucus gland layer increases)
- increased globlet cells in small bronchi and bronchioles and extensive small airway mucous pluging
chronic bronchitis morphologic changes
chronic bronchitis clinical:
persistent productive cough
dyspnea on exertion
classically:
-hypercapnia
-hypoxia
-mild cyanosis
Chronic disorder of the conducting airways, characterized by:
◦ Recurrent bronchoconstriction, associated with a variety of stimuli
◦Inflammation of bronchial walls
◦Increased mucus secretion
asthma
symptoms of asthma include
- recurrent wheezing, shortness of breathe/chest tightness, cough
- more frequent at night/early morning
atopic asthma
type I (IgE-mediated) hypersensitivity reaction
usually onset in childhood
atopic asthma is triggered by
pollen
animal dander
dust
food
Patients may have high serum IgE, a positive skin test for the
inciting allergen, or may demonstrate IgE antibodies to
specific allergens, and often have a family history of it
atopic asthma
atopic asthma Sensitization occurs when a ______ in response to antigen presentation, stimulate production of _____, recruits _____, and stimulates ____production
Th2 cell
IgE
recruits eosinophil
stimulates mucus production
in Atopic asthma pathogenesis, IgE binds to Fc receptors on______
triggers degranulation and inducing the immediate hypersens reaction
mast cells
atopic asthma
The immediate phase (minutes) is characterized by
- bronchoconstriction
- mucus secretion
- increased vascular permeability
atopic asthma
late phase (hours) characterized by
◦ Recruitment of more inflammatory cells (neutrophils, eosinophils,
lymphocytes)
◦ Results in damage to the mucosal tissue
non-atopic asthma
-bronchoconstriction also triggered b variety of stimuli such as
-respiratory viruses
-inhalation of irritants (smoke)
-cold air
-exercise
Asthma: morphologic changes
repeated allergen exposure and reaction induces airway remodeling
◦ Bronchial wall smooth muscle hypertrophy and hyperplasia
◦ Subepithelial fibrosis
◦ Submucosal gland hyperplasia; increased goblet cells
◦Increased airway vascularity
◦Increased thickness of the airway wall
asthma morphologic changes from repeated allergen exposure and rxn induces these
in asthma for morph changes, In severe cases, bronchi and bronchioles become occluded by _______, which may be expelled in sputum or
BAL specimens (Curschmann spirals)
thick mucus plugs
(Curschmann spirals)
Asthma: morphologic changes
Sputum and BAL specimens may also contain numerous
eosinophils and charcot-leyden crystals (especially in atopic cases)
Acute asthma attacks may last ____, but some patients
may experience symptoms at a lower baseline level
constantly
hours
In severe acute asthma (status asthmaticus), the attack may
last for ____ and result in obstruction sufficient to cause ____.
days
death
Chronic, recurrent necrotizing infections eventually destroy
smooth muscle and elastic tissue, leading to permanent
dilation of bronchi and bronchioles.
bronchiectasis
The infection, with associated inflammation and destruction
may follow obstruction and impedance of normal drainage;
or severe bronchial infections may cause enough
inflammatory damage and necrosis to bring about the
bronchiectatic changes.
bronchiectasis
bronchiectasis predisposing conditions
conditions affecting mucus clearing (primarily ciliary dyskinesia, cystic fibrosis, other bronchial obstruction)
-immunodeficiency conditions
with bronchiectasis, repeated attempts to resolve the inflammatory process may result in
peribronchial fibrosis
-may be extensive enough to obliterate nearby bronchioles (bronchiolitis obliterans)
Nontumor lung diseases in the setting of exposure to
mineral dusts, inorganic and organic particles, and chemical
fumes
particle size (1-5um most pathogenic)
penumoconioses
Inhaled carbon dust is taken up by macrophages, which
accumulate in interstitial tissue along pulmonary lymphatic
tissue
-seen in smokers and urban dwellers
-cause centriacinar emphysema
coal workers’ lung disease (pneumoconiosis)
black pigmented lesions formed by these coal
dust-containing macrophages
anthracosis
-progressive massive fibrosis
-characterized by multiple anthracotic scars, which if extensive, may lead to
respiratory failure, pulmonary hypertension, and RHF
complicated coal workers’ pneumoconiosis
-Caused by inhaling crystalline silicon dioxide over long
periods of time
-most common occupational disease worldwide!!
silicosis
in silicosis, Crystalline particles are ingested by ________, which
then mount an inflammatory response
◦ Slowly growing nodular collagenous scars
◦Over time these may coalesce → ______ ____ ___
macrophages
progressive massive fibrosis
Silicosis morphology
The nodular scars may occur in the
lungs or in hilar lymph nodes
are characteristically formed of whorled balls
of dense collagen fibers, surrounded by dust-containing
macrophages
-initially more prominent apically
-silica particles are birefringent with place-polarized light
The nodules of silicosis
leads to increased susceptibility to tuberculosis
and twice the risk of lung cancer compared to the general population
silicosis
refers to a group of fibrous hydrated silicate
crystals, known to cause interstitial and pleural fibrosis, and
lead to lung carcinoma and malignant mesothelioma
asbestos
two types:
serpentine and amphibole
- fibers are taken up by macrophages, which then
initiate an inflammatory response, leading to interstitial
fibrosis - The pattern of fibrosis is similar to that seen in usual
interstitial fibrosis, and may result in honeycomb lung
asbestos
asbestos characterized by the presence of ____ within macrophages
asbestos bodies
Plaques of dense collagen, sometimes calcified, may form
on the pleura, particularly the parietal pleura
Occasionally, asbestos exposure may result in pleural
effusion
asbestos
Very common: currently causing one sixth of deaths in the US
systemic conditions that are predisposers
◦Immunodeficiency (including leukopenia)
◦ Chronic disease
pulmonary infections
in pulmonary infections, Defense mechanisms specific to the lungs may also be
compromised:
-cough reflex
-impaired or diminished ciliary function
-mucus stasis
-decreased pulmonary macrophage activity
-pulmonary edema
Infections of bacterial pathogens may be indistinguishable
from viral, clinically and radiologically
-bacterial pneumonia may follow a viral URL
Predisposing conditions:
◦ Age: young or old
◦ Chronic disease (COPD, diabetes, CHF)
◦ Absent splenic function (predisposes toward encapsulated
bacterial infections)!!!!!!!!!!
Community-acquired bacterial
pneumonia
- Most common cause of community-acquired pneumonia
- ◦Important cause of pediatric bacterial pneumonia, otitis media
◦ Most common cause of bacterial acute exacerbation of COPD - ◦ Elderly: bacterial pneumonia, exacerbation of COPD
◦ Pediatric: otitis media - ◦Important cause of 2° bacterial pneumonia, following viral infection
◦ Higher incidence of complications (abscess, empyema) - ◦ Most common Gram negative bacterial pneumonia
◦ Chronic alcoholics, malnourished - ◦Important cause of pneumonia in cystic fibrosis, neutropenic
◦ Hematogenous spread - ◦ Water tanks, pipes
◦Immunosuppressed, chronic disease
◦ Urine Legionella antigen - children, young adults
- Streptococcus pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis
- Staphylococcus aureus
- klebsiella pneumoniae
- Pseudomonas aeruginosa
- legionella pneumophila
- mycoplasma
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Staphylococcus aureus
Klebsiella pneumoniae
Pseudomonas aeruginosa
legionella pneymonphila
mycoplasma pneumonia
Community-acquired bacterial pneumonia causative organisms
in Community-acquired bacterial pneumonia, the invasion of bacteria leads to alveolar filling with inflammatory cells and exudate resulting in
consolidation of the lung tissue (solidation)
occurs in two patterns:
bronchopneumonia
lobar pneumonia
◦ Patchy involvement of lung parenchyma
◦ Consolidated areas may coalesce
◦ Formed of acute suppuration
◦ Basal, often multilobar and frequently bilateral
brochopneumonia morph changes
◦ Consolidation occupies an entire lobe
◦ Four stages:
◦ Congestion: vascular engorgement, cell-poor intraalveolar fluid with bacteria
◦ Red hepatization: robust exudate with neutrophils,
erythrocytes, fibrin
◦ Grey hepatization: fibrinosuppurative material,
erythrocyte disintegration, early organizatinon
◦ Resolution: organizing fibrosis admixed with
macrophages
Lobar pneumonia
Presents with abrupt fever, shaking chills, productive cough
(rust colored sputum)
Lobar pneumonia x-ray: opaque lobe
Bronchpneumonia x-ray: focal opacities
Complications include:
◦ Abscess
◦ Empyema (pleural involvement)
◦ Bacteremia
Community-acquired bacterial
pneumonia
Community-acquired viral pneumonia common organisms
influenza virus A, B, C, RSV, human metapneumovirus, adenovirus, rhinoviruses, coronaviruses
covid 19 transmission thru
respiratory droplets
major cause of influenza epidemics and pandemics
-Generally infection involves the upper respiratory tract as
well, which facilitates spread
Virus infects respiratory epithelium; lung infection may be
patchy or extensive
this type infect humans, swine, birds, and horses=
influenza virus
type A
Causative organism: Mycobacterium tuberculosis
tuberculosis
person to person via airborne droplets
what tuberculosis
- Infection of a previously unexposed (and unsensitized) patient
- development of a Gohn complex
- 5% will develop disease
- results in focus of pulmonary scarring
primary tuberculosis
which tuberculosis
1. Arises in a previously sensitized host, from dormant primary
lesions
2. multiple lesions involving the apices of one or both lungs
3. military TB
Pott disease
secondary tuberculosis
◦Occurs in a debilitated patient, with diminished swallowing reflex
◦ Aspirated gastric content → abscess
◦ Usually more than one organism, usually anaerobes
aspiration pneumonia
◦ Patients typically very ill, often on a ventilator
◦Often immunocompromised
◦ Enterobacteriaceae, Pseudomonas, S. aureus
hospital-acquired pneumonia
is the most common
cause of cancer mortality world wide
◦Overall 5 yr survival 16%
lung
-Strong association with tobacco smoke
-High frequency of p53 mutations and overexpression
-Often preceded in bronchial epithelium by squamous
metaplasia, dysplasia, and carcinoma in situ
-Most often arise in the central lung/hilar region
squamous cell carcinoma
- May occur in smokers or nonsmokers
- More likely to be peripheral
- Gain of function mutations involving growth factor receptor
pathways - Precursor lesions
adenocarcinoma
-Strongest association with smoking
-Frequent TP53 and RB mutations
-Aggressive, very high rate of fatality
-May arise centrally or peripherally, likely from neuroendocrine*
cells in the bronchial epithelium
small cell carcinoma
Tumor cells are “small” with little cytoplasm, closely-arranged
nuclei with “molding” and absent nucleoli
Cells grow in clusters without any architectural pattern
Necrosis may be marked
small cell carcinoma
-Poorly-differentiated subtype
of NSCC, without
neuroendocrine, squamous or
glandular differentiation
-Diagnosis of exclusion, and
accounts for approximately
10% of cases
large cell carcinoma
-Any type of lung cancer may spread to the pleural space
-May spread hematogenously or within lymphatics
-metastasis occur widely to
>50% adrenal glands
then liver
metastatic lung carincoma
is the most common site of tumor metastasis
lung
Part of a spectrum of tumors arising from bronchial
neuroendocrine cells
carcinoid tumor
Carcinoid syndrome, caused by tumor cells secreting
vasoactive amines (serotonin), resulting in
◦ Flushing
◦ Diarrhea
◦ Cyanosis
carcinoid tumor
-Increased incidence with asbestos exposure, compounded
by smoking
-Most common mutational abnormality is homozygous
deletion of p16, seen in 80%
-arises from visceral or parietal pleura,
spreads in the pleural space, eventually ensheathing and
compressing the lung
- 1 year survival is 50%, most dont survive 2 years
malignant mesothelioma
-Squamous-lined fronds with fibrovascular cores
-May be single or multiple, and may occur in children and in
adults
-Caused by HPV types 6 and 11
-Benign, but may recur
squamous papillomas
- Squamous cell carcinoma, typically in men, 50s, smokers
- Thought to arise from dysplastic squamous epithelium
◦ Squamous hyperplasia > dysplasia > carcinoma - Carcinoma often forms a bulky, fungating mass protruding
from the laryngeal surface, often with ulceration
laryngeal carcioma
