1. MBChB, HSD, JBPath, EuroBPath
RESPIRATORY SYSTEM By
Dr. Nazar M.T. Jawhar
MBChB, HSD, JBPath, EuroBPath
Lecturer & consultant pathologist
European Board in pathology
Jordanian Board in pathology
Ph.D university of Jordan

3. Pulmonary restriction:
This is in contrast to obstructive defect, restrictive defect occurs in two general conditions:

4. Interstitial lung diseases.
Extrapulmonary disorders that affect the ability of the chest wall to act as a bellows, as:
- Severe obesity.
- Kyphoscoliosis.
- Neuromuscular disorders (as the Guillain Barre syndrome), that affect the respiratory muscles.

5. Microanatomy of alveolar wall:

6. RESTRICTIVE (INTERSTITIAL) LUNG DISEASES
This is a group of interstitial lung diseases that characterized by reduce lung compliance ( i.e more pressure is needed to expand the lungs because they are stiff ), no airway obstruction.

7. Acute restrictive lung disease: Chronic restrictive lung disease:
It occurs in two forms: acute & chronic.
Acute restrictive lung disease:
It characterized by rapid onset of respiratory dysfunction and development of pulmonary edema.
Example adult respiratory distress syndrome (ARDS).
Chronic restrictive lung disease:
Characterized by insidious onset and the development of chronic inflammation and interstitial fibrosis.
Include pneumoconiosis, sarcoidosis, and idiopathic pulmonary fibrosis.

8. ARDS:
This is a syndrome that characterized clinically by rapid onset of respiratory distress and arterial hypoxemia, and pathologically by diffuse alveolar damage.
Causes:

9. Infection
Sepsis*
Diffuse pulmonary infections*
Viral (as SARS), Mycoplasma, and Pneumocystis pneumonia; miliary tuberculosis
Gastric aspiration*
Physical Injury
Mechanical trauma, including head injuries*
Near-drowning
Fractures with fat embolism
Burns, Ionizing radiation
Inhaled Irritants
Oxygen toxicity, Smoke, Irritant gases and chemicals
Chemical Injury
Heroin or methadone overdose
Barbiturate overdose, Organic solvents
Hematologic Conditions
Multiple transfusions
Disseminated intravascular coagulation
Other as Pancreatitis, uremia, cardiopulmonary bypass,..

10. PATHOGENESIS:
The conditions that lead to ARDS cause either endothelial or alveolar epithelial damage.
Inflammatory cells will accumulate with subsequent release of powerful mediators ( like oxygen-derived free radicals, proteases, ….) which cause damage to the endothelium ( and/or alveolar epithelium) resulting in increased vascular permeability with subsequent edema

11. Morphology:
The most characteristic feature is formation of hyaline membrane lining the alveoli.
It consists of protein-rich edema fluid and necrotic epithelial cells.

12. Early phase of diffuse alveolar damage (DAD)
Early phase of diffuse alveolar damage (DAD). There are hyaline membranes, lining alveoli. High oxygen tensions needed to treat the hypoxia resulting from DAD and its etiologies further potentiates this disease.

13. Clinically:
The most important feature is dyspnea with severe acute respiratory failure, hypoxemia, and multiorgan failure.
Mortality rate may reach 50%.

14. Chronic restrictive lung diseases (Interstitial Pulmonary fibrosis)
A heterogeneous group of chronic diseases characterized by diffuse interstitial fibrosis affecting mainly alveolar wall.
Patients usually have dyspnea, tachypnea, and cyanosis WITHOUT wheeze or other evidence of airway obstruction WHY?
Radiologically: Diffuse infiltration by small nodules or irregular lines.

15. Causes of interstitial pulmonary fibrosis:
Some cases are of known etiology and many are of unknown etiology. Known causes include:

16. Occupational & environmental dusts :
Most common.
Inorganic dusts (pneumoconioses): coal, silica, asbestos, beryllium…..etc.
Organic dusts (hypersensitivity pneumonitis): as avian proteins ( birds fancier's disease).
Inhalants: fumes, gases,….

17. 2) Collagen vascular diseases: as RA, SLE, scleroderma, …….
3) Sarcoidosis.
4) Drugs and toxins: as chemotherapeutic agents (busulphan, methotrexate,..).
5) Ionizing radiation.
6) Infections: postpneumonic (viral and fungal).
4) Idiopathic.

18. Pathogenesis:
The initial stimuli (as occupational exposure, drugs,…etc) cause injury to the pneumocytes and/or endothelial cells with resultant accumulation of inflammatory cells ( mainly macrophages) within the alveoli, i.e alveolitis. Such accumulation has two consequences:
Release of chemical substances that cause damage to the alveolar wall as proteases, oxygen free radicals…
Secretion of cytokines (e.g IL-1,TNF) which stimulate fibrosis.

19. Morphology:
The main changes are seen in the interstitium.
Diffuse and progressive fibrous thickening of the alveolar walls leading to scarring and gross destruction of the lung, ending in “honeycomb lung”.

20. Clinically:
Insidious onset of non-productive cough and progressive dyspnea.

21. PNEUMOCONIOSES
lung reaction to inhalation of mineral dusts, mostly at work, therefore also called occupational lung diseases.
The four most common types of pneumoconioses result form exposure to:

22. Exposure Agent Coal mining Coal dust Silicosis Silica Asbestos
Disease
Agent
Coal mining
Anthracosis
Simple coal worker pneumoconioses (macule).
Progressive massive fiborsis.
Coal dust
Foundry work, sandblasting, hardrock mining, stone cutting,…
Silicosis
Silica
Mining, milling, and fabrication; installation & removal of insulation
Asbestosis, pleural effusion & plaque, mesothelioma, carcinoma of the lung, larynx, stomach, colon.
Asbestos
Mining, fabrication
Berylliosis
Beryllium

23. The type of lung diseases varies according to the nature of inhaled dust . Some dusts are inert and cause no reaction and no damage , while other cause immunological damage & may predispose to T.B or neoplasm

24. Factors which determined the extent of damage:
Size and shape of particles especially 2-5 µm
Their solubility and physio–chemical characters
The amount of dust retained in the lungs
The additional effect of other irritants such as tobacco smoke
Host factor such as efficiency of clearance mechanism and immune status of the host .

25. Anthracosis & simple coal worker pneumoconiosis :
Simplest forms of pneumoconiosis , usually universal , harmless , rarely it may progress to progressive massive fibrosis.

26. Silicosis :
May be encountered in sandblasting, mining, stone cutting, tunneling, ceramics, quarry mining,...
It induces progressive inflammation lead to the formation of fibrotic masses .
It may associated with increased susceptibility to T.B & lung cancer.

27. Collagenous silicotic nodule

29. Sarcoidosis
Definitions:
It is a multisystem disease of unknown etiology characterized by noncaseating granulomas in many tissues and organs. It is one of the cases of interstitial (restrictive) lung diseases.

30. Epidemiology:
Affects adults of both sexes.
It is more common in black people.
High prevalence among non-smokers.
Shows familial and racial clustering and association with certain HLA as HLA-A1 & HLA-B8.

31. Etiology & pathogenesis:
The etiology remains unknown.
Evidence suggest that it is a disease of disordered immune regulation (cell mediated immune response to unidentified antigen ) in genetically predisposed individuals exposed to certain environmental agents.
The process is driven by CD4 helper/inducer T-cells, which accumulate in the pulmonary interstitium, secrete cytokines (as IL-2 and interferon-γ), resulting in T-cell expansion and macrophage activation.

32. Morphology:
The histological hallmark of sarcoidosis is the presence of non-caseating epithelioid granuloma, irrespective of the organ involved.
WHAT is granuloma?
These are compact nodular collection of epithelioid histiocytes, rimmed by an outer zone of lymphocytes (CD4 helper). Scattered multinucleated giant cell may be seen. More peripherally, a layer of fibroblasts is present, which proliferate and lay down collagen that replace the granuloma.

34. Skin involvement: erythema nodosum and subcutaneous nodules.
Organs involved:
Lymph nodes: 75-90% of cases. Intrathoracic and paratracheal lymph nodes. In 30% of cases peripheral lymph nodes.
Lungs: In 90% of cases. Multiple granulomas in the interstitium ending in interstitial fibrosis and development of core plumonale.
Skin involvement: erythema nodosum and subcutaneous nodules.

35. Eye and lacrimal glands involvement: iritis and iridocyclitis (causing corneal opacity and glaucoma), choroditis, retinitis, and optic nerve involvement (blindness). Inflammation of the lacrimal glands may suppress lacrimation (sicca syndrome).
Salivary glands: Painful enlargement of the parotid glands and may leads to xerostomia (dry mouth).
Hepatic, splenic, and bone marrow involvement.
Virtually any organ may be involved such as the heart.

36. Clinical course:
Asymptomatic and discovered accidentally by routine chest x-ray (hilar LN enlargement).
Respiratory symptoms ( cough, dyspnea,..)
Peripheral lymphadenopathy, cutaneous lesions, eye involvement, or heptosplenomegally.
Constitutional symptoms as fever, fatigue, weight loss,…
Mikulicz syndrome WHY? (combined uveoparotid enlargement).

37. Diagnosis:
Demonstration of non-caseating granuloma in lung or lymph node biopsy.
However, other causes of granuloma as mycobacterial and fungal infection and berylliosis have to be rolled out.

38. Prognosis:
Progressive chronic course with episodes of relapse and remission.
60-70% of patients recover (steroid therapy) with no residual manifestations.
20% develop permanent lung dysfunction or visual impairment.

40. Vascular lung diseases

41. Pulmonary thromboembolism and infarction:

42. Embolization of venous and right-sided cardiac thrombi to the lung is an extremely important clinical problem.
It is the most common preventable cause of death in hospitalized patients. ( In USA account for 50,000 deaths per year).
Even when not directly fatal, it can complicate the course of other diseases.

43. More than 95% of all pulmonary embli arise from thrombi within the large deep veins of the lower legs.
Typically originating in popliteal veins and larger veins above it.

44. Predisposing factors for venous thrombosis in the leg:

45. Prolonged bed rest (especially with immobilization of the legs).
Surgery on the leg ( knee and hip surgery).
Severe trauma ( as severe burns and fractures).
Congestive heart failure.
Women in the period around parturition or who take oral contraceptive pills with high estrogen.
Disseminated cancer.

46. Pathophysiologic consequences of thromboembolism in the lung:
Depends on:
The size of the embolus which determine the size of the occluded vessels.
Cardiopulmonary status of the patient.

47. Occlusion of a major vessel results in sudden increase in pulmonary artery pressure, diminished cardiac output, acute right sided heart failure (acute cor pulmonale) or even death. Hypoxemia develops.
Occlusion of small vessels causes less catastrophic consequences and may be silent.
Occurrence of pulmonary infarction is exceptional and seen in only 10% of cases of pulmonary embolism, WHY?

48. Hemorrhagic pulmonary infarct.
Large saddle pulmonary embolus

49. Clinical course of pulmonary embolism:
Clinically silent (60-80% ): Small emboli removed by:
Sudden death (5%): when >60% of the pulmonary vasculature is obstructed by large embolus ( saddle embolus). Acute right sided heart failure or cardiovascular collapse.
Pulmonary infarction (10-15%) , obstruction of medium sized end artery. Usually in the lower lobes and has a wedge-shape (the base is on the pleura), clinically:
Pulmonary hypertension and core pulmonale.(<3%), recurrent multiple emboli.

50. Patients who have experienced one pulmonary embolus have a 30% chance of developing a second.
Prophylactic therapy:
Early ambulation for postoperative and postpartum patients.
Elastic stockings.
Isometric leg exercises for bedridden patient.
Anticoagulation for persons at risk.