Intro to lung pathology for nurses and dental students

1. PATHOLOGY
BASIC INTRODUCTION TO PATHOLOGY OF COMMON LUNG DISEASES
DISEASES
FOR
UNDERGRADUATE DENTAL STUDENTS AND NURSES
REFERENCE: ROBBINS BASIC PATHOLOGY, 9TH EDITION.
Dr. Sufia Husain
Pathology

2. Lecture outline
Introduction to
o Bronchial asthma
o Chronic bronchitis and Emphysema
o Bronchiectasis.
o Pneumonia
o Tuberculosis
o Lung tumors

3. RESPIRATORY TRACT
Background information

4. RESPIRATORY TRACT
Background information
Function of lungs….
Gas exchange (O2, CO2)
■ Can only occur in alveoli that
are both ventilated and
perfused

5. RESPIRATORY TRACT
Background information

6. BRONCHIAL ASTHMA

7. BRONCHIAL ASTHMA (BA)
• Most common chronic respiratory disease in children.
More common in children than adults
• Is a chronic episodic inflammatory obstructive lung
disease characterized by hyper-reactive airways
(patients have hyper-irritable airways which react to
various stimuli).
• Primarily targets the bronchi and terminal bronchioles
• In it the airways go into bronchoconstriction/spasm.
• It results in a triad of:
1. intermittent and reversible airway constriction
2. Edema, inflammation with eosinophils and excess
mucus production
3. bronchial smooth muscle cell hypertrophy
C/F of BA
 In a classic asthmatic attack there is wheezing,
dyspnea, cough.
 Nocturnal cough

8. Complications of Bronchial Asthma
 Superimposed infection
 Chronic bronchitis or Emphysema
 Status asthmaticus:
•most severe form of asthma  severe acute
respiratory distress
•severe bronchoconstriction that does not respond
easily to drugs.
•serious and requires hospitalization and may 
severe cyanosis and death.
Extrinsic (atopic, allergic) Asthma 70% Intrinsic (non-atopic)Asthma 30%
Allergic type 1 hypersensitivity reaction induced by
exposure to extrinsic antigen/allergens e.g. food, pollen,
dust, etc.
Non- allergic.
Usually family history present No personal history of allergy.
No family history of allergy.
Develop early in life Develops later in life
Sometimes extrinsic and intrinsic can co-exist in the same

9. CHRONIC
BRONCHITIS

10. Chronic Bronchitis
 Common among cigarette smokers and urban dwellers, age 40 to 65
 Definition  persistent productive cough (with sputum) for at least 3
consecutive months in at least 2 consecutive years
 Can coexists with emphysema (Often, there are features of emphysema
as well)
Causative factor are:
– Cigarette smoking and pollutants.
– Infection
– Genetic factors

11. EMPHYSEMA

12. Emphysema
 Is abnormal permanent enlargement of the
airspaces distal to the terminal bronchioles
accompanied by destruction of their walls,
without obvious fibrosis.
 Tends to coexist with chronic bronchitis
 Types of emphysema:
– Centriacinar (centrilobular) : Occurs in
heavy smoker in association with chronic
bronchitis
– Panacinar: there is Alpha 1 antitrypsin
deficiency
– Distal acinar /paraseptal
– Irregular
Clinical features:
• Cough and wheezing. Respiratory acidosis
• Abnormal pulmonary function tests

13. ■ Normal ■ Emphysema
Morphology: The lungs are pale, voluminous. Histology thinning
and destruction of alveolar walls creating large airspaces.

14. Centriacinar (centrilobular) emphysema
■ Occur in heavy smoker in association with chronic bronchitis
■ The central or proximal parts of the acini are affected, while distal
alveoli are spared

15. Panacinar (panlobular) emphysema
 Cause: occurs in 1-anti-trypsin deficiency.
 Uniform injury: Acini are uniformly
enlarged from the level of the respiratory
bronchiole to the terminal blind alveoli.

16. Distal acinar (paraseptal) emphysema
■ The proximal portion of the acinus is
normal but the distal part is dominantly
involved.
■ Sometimes forming multiple cyst-like
structures with spontaneous
pneumothorax.

17. Pathogenesis of Emphysema
 Normally there is a balance between protease and anti protease
activity.
 An imbalance between protease and antiprotease activity in the
lung  emphysema.
 Protease (e.g. elastase) is proteolytic enzymes that damages
alveolar elastic tissue. It is produced by neutrophils and
macrophages.
 Smokers have increase in the numbers of alveolar macrophages
and neutrophils  imbalance.
 Note: Alpha 1 antitrypsin is an anti-protease. It is normally
present in the serum, in tissue fluids and in macrophages.
Deficiency  panacinar emphysema.

18. Emphysema: Morphology
■ The lungs are pale, voluminous.
■ Histologically: thinning and destruction of alveolar walls
creating large airspaces.
Clinical features:
• Cough and wheezing. Respiratory
acidosis
• Weight loss.
• Pulmonary function tests reveal
reduced FEV1.

19. BRONCHIECTASIS

20. Bronchiectasis
 is chronic necrotizing inflammation and destruction of the bronchi and bronchioles  leading to
abnormal permanent dilation of these airways.
 most often involves the lower lobes of both lungs.
 characterized by
• fever and cough
• production of purulent foul smelling sputum,
• and recurrent pulmonary infection that may lead to lung abscess.

21. Normal
■ Airways are dilated airways up to four times of normal.
Bronchiectasis

22. Morphology of Bronchiectasis
■ Usually affects lower lobes bilaterally.
■ Dilated airways up to four times of normal.
■ Acute and chronic inflammation
(neutrophils, lymphocytes, histiocytes and
plasma cells)
■ Necrosis and ulceration in the wall of the
bronchi and bronchioles and fibrosis.

23. PNEUMONIA

24. Pneumonia
 Pneumonia is defined as any infection of lung parenchyma
 Portal of entry for most pneumonia is
 Inhalation of air droplets
 Aspiration of infected secretions or objects
 Hematogenous spread.
Pneumonia can be acute or chronic
Histology: variable, can be:
acute fibrinopurulent alveolar exudate
chronic interstitial inflammation
 granulomatous inflammation

25. CLASSIFICATION OF PNEUMONIA
1. Bronchopneumonia:
■ occur in two extremes of life.
■ multiple small patches of
inflammation centered around
bronchioles.
2. Lobar pneumonia:
• acute infection of a large portion of a
lobe or entire lobe (widespread
fibrinosupurative consolidation).
- Note: overlap of the two patterns often occur

26. Stages of pneumonia
There are 4 stages:
I. Congestion: lung is heavy, boggy and red. The alveoli are filled with fluid and bacteria.
II. Red hepatization: the lung is firm/solid, red and alveoli are filled with neutrophils, rbcs
(congestion) and fibrin.
III. Gray hepatization: the red cells are reduced but neutrophils and fibrin (fibrinopurulent/suppurative
exudate) are still present. The lung is still firm/solid but grey.
IV. Resolution
(hepatization = solidification = liver like consistency)

27. Red hepatization

28. Opportunistic pneumonias
• Infections that affect immunosuppressed patients (AIDS, cancer patients and
transplant recipients)
Causative organisms:
• Cytomegalovirus
• Pneumocystis jiroveci (formerly P. carinii)
• Mycobacterium avium-intracellulare
• Invasive aspergillosis
• Invasive candidiasis
• "Usual" bacterial, viral, and fungal organisms
Pneumocystis carinii
Aspergillus
Cytomegalovirus
 Methods of diagnosis are:
 identify the organism in bronchoalveolar
lavage fluids or in a transbronchial biopsy
specimen.
 Culture
 PCR-based assays.

29. TUBERCULOSIS

30. TUBERCULOSIS
■ TB is a communicable granulomatous disease caused mainly by Mycobacterium
tuberculosis hominis (Koch bacillus) and occasionally by Mycobacterium tuberculosis
bovis.
■ Primarily affects the lungs but other organs can also be infected.
■ Reservoir of infection is humans with active tuberculosis.
■ Characteristic lesion: epitheloid granuloma with central caseous necrosis.
■ Mycobacterium tuberculi are non-motile rod-shaped aerobic acid fast bacilli.

31. TUBERCULOSIS
Reservoir of infection:
• humans with active tuberculosis.
Increased risk:
• poverty, crowding, malnutrition, chronic debilitating illness,
elderly, people with AIDS, immunosuppression etc.
Route of transmission
• M. tuberculosis generally enters lung by inhalation (by
inhaling infected aerosols from the cough of a person with
active cavitatory TB).
• M. bovis generally enters by drinking unpasturized infected
cow's milk  oropharyngeal & intestinal TB.
Clinical features
• Malaise, anorexia, weight loss, fever (low grade evening rise
of temperature) with chills and night sweats.
• Cough with sputum, hemoptysis etc.
• Extrapulmonary manifestations of tuberculosis depend on
the organ system involved.
• Localized secondary tuberculosis may be asymptomatic.

32. Cavitatory TB lung
Cavitatory tuberculosis with intracavitary
hemorrhage. Extensive necrosis with
cavitation, usually occurring in the upper
lung lobe .

33. Langhans Giant Cell
Caseous Necrosis
Epithelioid Macrophage
Lymphocytic Rim

34. Diagnosis of TB
Ziehl-Neelsen stain shows red acid-fast
staining M. tuberculi.
Tubercle bacilli are acid fast:
 Characteristically the bacilli stain red/pink with
Ziehl-Neelsen acid-fast stain and the glow with
fluorescent dye auramine O.
 TB culture of the sputum or tissue is still the
most sensitive and specific, albeit slowest, way
to make the diagnosis. Culture is the gold
standard
 PCR testing allows for rapid diagnosis.

35. LUNG TUMORS

36. Lung Tumors
■ Most lung tumors are malignant.
■ Lungs are frequently the site of metastases.
■ Primary lung cancer is a common disease BUT metastatic tumors are more
common than the primary tumors.
■ The most common benign lesions are hamartomas.

37. Examples of Primary Lung Tumors
MALIGNANT EPITHELIAL TUMORS /BRONCHOGENIC CARCINOMA:
I. Non-Small Cell Lung Carcinoma
a) Squamous cell carcinoma: Strong association with smoking, poor prognosis, usually
central (perihilar) in location, can be well/ moderate/ poorly differentiated
b) Adenocarcinoma: do not have a clear link to smoking history, usually peripheral in location,
sometimes associated with pulmonary scars (scar carcinoma)
c) Large cell carcinoma: uncommon, strongly associated with smoking, very poor prognosis.
II. Small cell lung carcinoma: poorly differentiated highly malignant, aggressive neuroendocrine tumors.
Poor prognosis. Strongly associated with cigarette smoking. Central (perihilar), can be associated
with paraneoplastic syndrome. Microscopy  small round blue cells.
III. Combine patterns
IV. Carcinoid tumor: well differentiated neuroendocrine tumor; not related to cigarette smoking. Tumor cells
produce serotonin and bradykinin  carcinoid syndrome (flushing, wheezing, diarrhea etc.), can
also produce ectopic ACTH  Cushing syndrome. Low malignancy, good prognosis (often resectable
& curable).
MALIGNANT MESOTHELIAL TUMOR: malignant mesothelioma
OTHERS Miscellaneous malignant tumor e.g. Carcinosarcoma, Pulmonary blastoma, Melanoma,
Lymphoma etc

38. BRONCHOGENIC CARCINOMA
Bronchogenic carcinoma is a malignant neoplasm
of the lung arising from the epithelium of the lung.
Most patients are 50-80 years.
For therapeutic purposes, bronchogenic carcinoma
are classified into:
1. Non- Small cell lung carcinoma (NSCC)
2. Small cell lung carcinoma (SCC)
Important to differentiated between the 2
because treatment are different.
For NSCC therapy:
•Surgical - the best chance for curing.
•Radiation – to control local disease.
•Chemotherapy – not effective.
SCC therapy
•Chemotherapy - very effective, small cell
carcinomas are highly responsive to
chemotherapy

39. SO: It is important to differentiated between the Non-small cell and small cell because treatment is different:
• Non- Small cell lung carcinoma (NSCC)  surgery
• Small cell lung carcinoma (SCC)  chemotherapy is very effective

40. Squamous cell carcinoma
(SqCC)
■ strong association with smoking
■ Poor prognosis
■ SqCC arise in the central airways (centrally
located). So they appears as a hilar mass.
■ Tumor cells secrete a parathyroid hormone
(PTH)- like peptide  hypercalcemia.
■ Histologically they are graded according to
degree of squamous differentiation:
• well-differentiated SqCC
• moderately differentiated SqCC
• poorly differentiated SqCC

41. adenocarcinomas
■ They do not have a clear link to
smoking history
■ They are classically peripheral tumors
arising from the peripheral airways and
alveoli.
■ The hallmark of adenocarcinomas is
the tendency to form glands that may
or may not produce mucin.
■ Peripheral adenocarcinomas are
sometimes associated with pulmonary
scars (from a previous pulmonary
inflammation/infection) and therefore is
also referred to as scar carcinoma.

42. Large Cell
Carcinoma
■ Frequency: 10%
■ strongly associated with smoking
■ usually located peripherally.
■ poor prognosis.

43. Small cell carcinomas
■ SCLC are a poorly differentiated highly malignant
neuroendocrine tumors arising from
neuroendocrine cells.
■ Highly malignant and aggressive tumor, poor
prognosis.
■ Strongly associated with cigarette smoking.
■ Centrally located perihilar mass.
■ Microscopically composed of small, round dark
blue cells.
■ Chemotherapy responsive
■ It may be associated with paraneoplastic
syndrome.

44. Carcinoid tumor
■ Carcinoid tumors of the lung are well differentiated
neuroendocrine tumor. They arise from the
neuroendocrine cells found in the bronchial epithelium.
■ These neoplasms account for 2% of all primary lung
cancers and are not related to cigarette smoking.
■ Can be central or peripheral in location
■ Composed of uniform cuboidal cells that have regular
round nuclei with few mitoses and little or no atypia.
■ Electron microscopy: dense-core neurosecretory
granules.
■ Tumor cells produce serotonin and bradykinin leading
to carcinoid syndrome (flushing, wheezing, diarrhea,
and cardiac valvular lesions).Tumor cells can also
produce ectopic ACTH leading to Cushing syndrome.
■ Can occur in patients with Multiple Endocrine
Neoplasia (MEN-I)
■ Low malignancy, Often resectable and curable.
■ Spreads by direct extension into adjacent tissues

45. Etiology of bronchogenic carcinoma
1. Tobacco smoking: cigarette smoking is linked to squamous cell carcinoma and small cell
carcinoma. The risk is 20 to 40 times greater among habitual heavy smokers. Passive
smoking increases the risk to approximately twice than non-smokers. The nonsmoker
who develops cancer of the lung usually  adenocarcinoma.
2. Radiation
3. Asbestos exposure  bronchogenic carcinoma and mesothelioma.
4. Industrial exposure to nickel and chromates, coal, mustard gas, arsenic, iron etc.
5. Air pollution: may play a role e.g. indoor air pollution by radon.
6. Scarring: sometimes old infarcts, wounds, scar (from a previous pulmonary
inflammation/infection), granulomatous infections are associated with adenocarcinoma.

46. Clinical features of bronchogenic carcinoma
 Can be silent or insidious lesions
 Respiratory symptoms e.g. Cough, expectoration, hemoptysis, bronchial obstruction, lung collapse,
bronchiectasis, pneumonia, chest pain, pleural effusion etc.
 Hoarseness, chest pain, superior vena cava syndrome, pericardial or pleural effusion.
 Paraneoplastic syndrome: are extrapulmonary, remote effects of tumors. About 10% of lung cancers develop
paraneoplastic syndromes. In it the tumor cells produce various peptides/hormone  lead to metabolic and
neuromuscular disturbances e.g.
Carcinoid tumors and small cell carcinomas may secrete ectopic ACTH  Cushing's syndrome
small cell carcinomas may secrete ADH  water retention and hyponatremia
squamous cell carcinomas may secrete PTH like peptide  hypercalcemia.
Etc.

47. Mesothelioma
■ Highly malignant tumor of mesothelial
cells lining the pleura
■ History of exposure to asbestos is
common.
■ Treatment is largely ineffective and
prognosis  extremely poor

48. Metastatic carcinoma of lung
■ Pulmonary Metastases are More
Common than Primary Lung Tumors
■ Typically multiple and circumscribed
nodules. Radiologically  called
cannon ball metastases.
■ The common primary sites are the
breast, stomach, pancreas, and colon.