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PATHOLOGY of the RESPIRATORY SYSTEM
Dr. Mohammad A.A. Al-Qudah
Soul batch

Lung pathology may involve any or all
of the following :
 The
airways
 The parenchyma & interstitium
 The pulmonary vascular system
Some diseases end in heart failure :
COR PULMONALE
 Many diseases may be accompanied by
ATELECTASIS

PATHOGENESIS : Alveolar septae structure
Atelectasis :
Loss of lung volume due to inadequate
expansion of airspace leading to ventilationperfusion imbalance → hypoxia.
 May involve : 1- Segment
2- Lobe
3- Lung
 Maybe reversible if cause is removed.

Types of Atelectasis :
1-Resorption atelectasis ( obstructive ) :
-Foreign body
-Mucus plug in asthma & chronic bronchitis
-Post surgery
-Tumor.
Mediastinal Shift to Same Side
2- Compression atelectasis : causes include
- Air or fluid in pleural cavity
- Elevated diaphragm
Mediastinal Shift to Opposite Side
Types of Atelectasis
Atelectasis
3- Contraction atelectasis :-
- Localized or generalized.
- Post inflammatory scarring.
- Fibrotic changes .
Usually irreversible.
4- Microatelectasis :
- Due to loss of surfactant.
- Usually generalized.
- Acute or Neonatal Respiratory
Distress Syndrome.
Note : No mediastinal shift in 3 or 4
Morphology of Atelectasis :
Gross :
- Shrunken, purple & subcrepitant lung. (nodular).
Microscopic :
- Slit like alveoli, congested septae ,fluid in spaces.
- Hyaline membranes in microetelectasis.
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Outcome of atelectasis depends on:
1- Cause (regardless of the type of atelectasis).
2- Size of involved area.
3- Duration to start treatment.
ACUTE LUNG INJURY
Acute Respiratory Distress Syndrome


Clinical syndrome that is caused by many conditions.
Clinical manifestations include:
 Sudden
and Acute onset of severe dyspnea.
 Hypoxaemia, hypercapnia.
 Diffuse bilateral pulmonary infiltrates (radiology).
** This will lead to respiratory failure.
- The above mentioned manifestations should happen in
the absence of left sided heart failure.


Again, it is a disease caused by many diseases that
might affect Endothelial or Epithelial cells in the
alveoli.
Acute Respiratory Distress Syndrome is a severe
form of acute lung injury.
ARDS:


Cause: diffuse alveolar (epithelia & endothelial) damage.
Cascade of reactions that will be activated more and
more by inflammation.
Rapid onset and life threatening condition.
Aetiology

Direct injury
 Pneumonia.
 Aspiration
of gastric contents.
 Toxic inhalation.

Indirect injury
 Sepsis.
*****
 Multiple trauma.
 Multiple
bone fractures
 Head trauma
 Severe Burns
 Multiple
transfusions.
 Drug overdose.
 Pancreatitis.
Aetiology


Sepsis & pneumonia account for 40-50% of cases
Risk factors:
 Multiple
pre-disposing medical conditions
specially with a severe critical illness
 Older age
 Chronic alcohol abuse
 Metabolic acidosis
 Many others
PATHOGENESIS : Alveolar septae structure
Pathogenesis :


Injurious agent ( airways or hematogenous)
Diffuse Alveolar Damage ( DAD )
- VASCULAR ENDOTHELIUM.
- ALVEOLAR EPITHELIUM.
Endothelium  permeability, severe edema.
Epithelium ↓surfactant  microatelectasis.
Injury is caused by imbalance of pro-inflammatory & antiinflammatory mediators.
• Nuclear Factor (NF-κB) activation is pro-inflammatory .

Activated macrophages IL-8, IL-1,TNF..etc
 Selection, isolation & activation of neutrophils in the
microcirculation.
 Neutrophils release oxidants, proteases,PAF ,
leukotrienes  tissue damage.
LATER :
Macrophage derived fibrogenic factors
( TGF, PDGF, IL-1, TNF)
Recruitment of fibroblasts → Fibrogenesis.
 All previous can be counteracted by
endogenous antiproteases, antioxidants
& anti - inflammatory cytokines(IL-10)
 Clotting cascade is also triggered.


PHASES of ARDS:

Acute phase:
 Accumulation
of protein-rich fluid in interstitium & alveoli,
most in dependent areas  diminished gas exchange and
atelectasis.
 Significant concentration of cytokines in lung  neutrophil
infiltration.**
 Plasma protein in air spaces with cellular debris and
dysfunctional surfactant  HYALINE MEMBRANES **
 Vascular injury  microthrombi & fibrocellular proliferation
 Pulm. HTN.
Hyaline membranes in ARDS

Organizing phase:
 Patients
may recover rapidly or may still experience
dyspnea,& hypoxaemia.
 Histology
 Organisation
of alveolar exudates.
 Lymphocyte-predominant infiltrate.
 Proliferation of Type II pneumocytes.

Fibrosis:
 Most
patients recover lung function after 3-4 weeks, but
some enter a fibrotic phase.
 Requires long-term mechanical ventilation and/or
supplementary O2.
 Histology
 Extensive
fibrosis.
 Disrupted architecture Emphysema like.
 Intimal proliferation of microcirculation  vascular
occlusion + pulmonary HTN.
 End
result is HONEY COMB LUNG
Honeycomb Lung
Clinical picture : Manifested as
Acute Respiratory Distress Syndrome
Acute severe dyspnea, rapid hypoxemia & cyanosis.
That usually develops within 72 hours of insult in 85% of
patients.
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Bilateral severe pulmonary edema in the absence of
left ventricular failure
Radiological evidence of bilateral pulmonary infiltrates
Multisystem failure, secondary infection & DIC.
Clinical Course:


Highly fatal in acute phase (30-40% )
- Prognosis is worse in old age.
- Bronchoalveolar lavage done to assess
level of IL-1 & Procollagen III
In patients surviving acute insult  restored
pulmonary function in 6-12 months.
DISEASES OF VASCULAR ORIGIN IN THE LUNG
VASCULAR PULMONARY DISEASES



PULMONARY EMBOLISM (with or usually WITHOUT
infarction).
PULMONARY HYPERTENSION, leading to cor pulmonale.
HEMORRHAGIC SYNDROMES
 GOODPASTURE


SYNDROME.
HEMOSIDEROSIS, idiopathic.
Pulmonary Angiitis (WEGENER GRANULOMATOSIS).
1- Pulmonary thromboembolism
- Preventable cause of death in hospital
- 95% originate from deep veins in legs
- Predisposing causes :
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Prolonged surgery.
Pregnancy or birth control pills ( estrogen).
Disseminated cancer.
Congestive Heart Failure.
Prolonged bed rest without moving legs.
Hypercoagulability states.
Outcome of occlusion :
Depends on size of vessel & state of circulation
i - Large in P.Trunk or Saddle embolus  Sudden Death
ii- Medium size, ischemic damage to capillaries or
occlusion 
Lung Hemorrhage OR Pulmonary Infarction
Morphology :
- Negative if sudden death.
- Wedge shaped necrosis ,thrombus in vessel , may
be with hemorrhage, fibrinous exudate on the
pleura.
- Fibrosis
Base of necrosis will be on the pleura, while the
apex will point toward the hilum of the lung.
Clinical Presentation of P.embolism:
- Asymptomatic (60-80%).
- If more than 60% reduction in blood flow  Acute
cor pulmonale &sudden death (5%).
- If in between: Sudden dyspnea, chest pain due to
infarction.
- Recurrent multiple emboli & infarcts leading to chronic
pulmonary hypertension (3%).
- One attack  30% increase of the risk to have
recurrent attacks.
2- Pulmonary Hypertension :
- Arises in one of two ways :
i- Decrease in the cross sectional area
of pulmonary vascular bed.
ii-Increase in pulmonary vascular flow.
- Primary OR secondary
Causes of secondary hypertension :
i - Cardiac disease
ii - Chronic lung disease
iii- Inflammatory vascular disease
iv- Recurrent thromboembolism
Primary Pulmonary Hypertension :
More in young females
 Familial & sporadic cases occur
 Probably genetic: TGF-β, 5-HTT
 Pathogenesis :
Endothelial cell dysfunction & smooth
muscle proliferation → vasoconstriction.
- Endothelin regulates the diameter of blood
vessels in the lungs.
- An increase in endothelin can cause the small arteries
in the lungs to narrow  pulmonary hypertension

Pathology of pulmonary hypertension
1- Main arteries  Atheroma.
2- Medium sized muscular arteries 
myointimal & smooth muscle
proliferation.
3- Small arteries & arterioles  medial
hypertrophy duplication elastic lamina.
4- In long standing primary cases 
Complicated Plexiform Lesions
 Poor prognosis unless lung transplant
Normal Capillary
Hyaline Arteriolosclerosis
Arteriolar wall is hyalinized and the lumen is markedly
narrowed in benign hypertension
3- Diffuse Alveolar Hemorrhage
Syndromes :
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Primary immune mediated diseases.
Clinically : Hemoptysis, Anemia,Diffuse pulmonary infiltrates.
Include several types e.g. Goodpasture’s Syndrome.
GPS:proliferative progressive Glomerulonephritis &
hemorrhagic interstitial pneumonitis.
Caused by Ab against collagen IV in BM.
4- IDIOPATHIC HEMOSIDEROSIS
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Similar histology to GP but no renal involvement.
Unknown cause.
No Anti Basement membrane antibodies.
5- Pulmonary Angiitis:
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Wegener granulomatosis.
80% of patients will develop lung manifestations.
Necrotizing vasculitis & granulomas.
Can present with upper respiratory tract manifestations.
(sinusitis, epistaxis).
If not involving kidney  Limited Wegener.