1. PATHOLOGY of the RESPIRATORY SYSTEM Dr. Mohammad A.A. Al-Qudah
Typical normal 1000 gram lung (R550, L450), with lobes and bronchopulmonary segments, primary, secondary, tertiary bronchi, etc. Pleura “smooth and glistening”, arteries traveling with bronchi, veins being rather independent of bronchopulmonary segments and lobes. Why is weight important? Why is “smooth and glistening” important? What is “crepitance”? Why is crepitance important?
PATHOLOGY of the RESPIRATORY SYSTEM
Dr. Mohammad A.A. Al-Qudah
Soul batch

2. 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

3. PATHOGENESIS : Alveolar septae structure

4. Atelectasis : Loss of lung volume due to inadequate
expansion of airspace leading to ventilation- perfusion imbalance → hypoxia.
May involve : 1- Segment
2- Lobe
3- Lung
Maybe reversible if cause is removed.

5. Types of Atelectasis : -Mucus plug in asthma & chronic bronchitis
1-Resorption atelectasis ( obstructive ) :
-Foreign body
-Mucus plug in asthma & chronic bronchitis
-Post surgery
-Tumor.
Mediastinal Shift to Same Side

6. - Air or fluid in pleural cavity - Elevated diaphragm
2- Compression atelectasis : causes include
- Air or fluid in pleural cavity
- Elevated diaphragm
Mediastinal Shift to Opposite Side

7. Types of Atelectasis

8. Atelectasis

9. - Localized or generalized. - Post inflammatory scarring.
3- Contraction atelectasis :-
- Localized or generalized.
- Post inflammatory scarring.
- Fibrotic changes .
Usually irreversible.

10. - Due to loss of surfactant. - Usually generalized.
4- Microatelectasis :
- Due to loss of surfactant.
- Usually generalized.
- Acute or Neonatal Respiratory
Distress Syndrome.
Note : No mediastinal shift in 3 or 4

11. Morphology of Atelectasis :
Gross :
- Shrunken, purple & subcrepitant lung. (nodular).
Microscopic :
- Slit like alveoli, congested septae ,fluid in spaces.
- Hyaline membranes in microetelectasis.

13. Outcome of atelectasis depends on:
1- Cause (regardless of the type of atelectasis).
2- Size of involved area.
3- Duration to start treatment.

14. ACUTE LUNG INJURY

15. 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.

16. 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.

17. 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.

20. Aetiology Pneumonia. Aspiration of gastric contents. Toxic inhalation.
Direct injury
Pneumonia.
Aspiration of gastric contents.
Toxic inhalation.

21. Multiple transfusions. Drug overdose. Pancreatitis.
Indirect injury
Sepsis. *****
Multiple trauma.
Multiple bone fractures
Head trauma
Severe Burns
Multiple transfusions.
Drug overdose.
Pancreatitis.

22. 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

23. PATHOGENESIS : Alveolar septae structure

24. Pathogenesis : Injurious agent ( airways or hematogenous)
Diffuse Alveolar Damage ( DAD )
- VASCULAR ENDOTHELIUM.
- ALVEOLAR EPITHELIUM.
Endothelium  permeability, severe edema.
Epithelium ↓surfactant  microatelectasis.

25. Injury is caused by imbalance of pro-inflammatory & anti- inflammatory 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.

26. 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.

27. PHASES of ARDS:

28. 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.

29. Hyaline membranes in ARDS

31. Organizing phase: Organisation of alveolar exudates.
Patients may recover rapidly or may still experience dyspnea,& hypoxaemia.
Histology
Organisation of alveolar exudates.
Lymphocyte-predominant infiltrate.
Proliferation of Type II pneumocytes.

32. Fibrosis: Extensive fibrosis. Disrupted architecture Emphysema like.
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

33. Honeycomb Lung

34. 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.
Bilateral severe pulmonary edema in the absence of left ventricular failure
Radiological evidence of bilateral pulmonary infiltrates
Multisystem failure, secondary infection & DIC.

35. 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.

36. DISEASES OF VASCULAR ORIGIN IN THE LUNG

37. 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).

38. 1- Pulmonary thromboembolism
- Preventable cause of death in hospital
- 95% originate from deep veins in legs
- Predisposing causes :
Prolonged surgery.
Pregnancy or birth control pills ( estrogen).
Disseminated cancer.
Congestive Heart Failure.
Prolonged bed rest without moving legs.
Hypercoagulability states.

39. 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

40. - Negative if sudden death.
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.

41. 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.

42. 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

44. Causes of secondary hypertension :
i - Cardiac disease ii - Chronic lung disease iii- Inflammatory vascular disease iv- Recurrent thromboembolism

45. 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

46. 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

47. Normal Capillary

48. Hyaline Arteriolosclerosis Arteriolar wall is hyalinized and the lumen is markedly narrowed in benign hypertension

49. 3- Diffuse Alveolar Hemorrhage Syndromes :
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.

50. 4- IDIOPATHIC HEMOSIDEROSIS
Similar histology to GP but no renal involvement.
Unknown cause.
No Anti Basement membrane antibodies.

51. 5- Pulmonary Angiitis: 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.