This document provides an overview of the anatomy, histology, and pathology of the respiratory system. It begins with the normal anatomy and histology of the lungs and trachea. It then discusses various pathological conditions including atelectasis, acute lung injury, diffuse pulmonary diseases such as obstructive diseases like emphysema and restrictive diseases like idiopathic pulmonary fibrosis. It also covers pulmonary infections, tumors, and diseases of vascular origin. For each condition, it provides details on pathogenesis, morphology, and clinical presentation.

1. 1
Evolution of the respiratory system

3. 3
Overview
 Normal Anatomy and Histology
 Pathology of diseases

4. 4
Source: Chapter 1. Function and Structure of the Respiratory System, Pulmonary Physiology, 8e
Citation: Levitzky MG. Pulmonary Physiology, 8e; 2013 Available at:
http://accessmedicine.mhmedical.com/content.aspx?bookid=575&sectionid=42512979 Accessed: February 21, 2018
Copyright © 2018 McGraw-Hill Education. All rights reserved
Schematic representation of airway branching in the human lung with approximate dimensions.
Anatomy of the Lungs

5. 5
Histology of the lungs
Trachea

6. 6
Histology of the lungs
https://www.proteinatlas.org/learn/dictionary/normal/lung

7. 7
Pathology of diseases – Overview
Atelectasis Obstructive Restrictive Vascular origin
1. Resorption
2. Compression
3. Contraction
1. Emphysema
2. Chronic bronchitis
3. Asthma
4. Bronchiectasis
1. Fibrosing diseases
2. Granulomatous
diseases
3. Pulmonary Eosinophilia
4. Smoking related
Interstitial diseases
1. Pulmonary embolism,
hemorrhage and
infarction
2. Hypertension
3. Diffuse alveolar
hemorrhage syndromesPulmonary infections
1. Community acquired acute pneumonia
2. Community acquired atypical pneumonias
3. Nosocomial pneumonia
4. Aspiration pneumonia
5. Lung abscess
6. Chronic pneumonia
7. Pneumonia in the immunocompromised host
8. Opportunistic fungal infection
9. Pulmonary infection in HIV infection
Lung tumors
Pleural lesions Lesions of the upper
respiratory tract
1. Carcinomas
2. Bronchial carcinoids
1. Pleural effusion and
pleuritic
2. Pneumothorax,
hemothorax and
chylothorax
3. Malignant
mesothelioma
1. Nasopharyngeal
carcinoma
2. Laryngeal tumors

8. 8
Atelectasis
 Collapse – loss of lung volume
 Resorption
 Obstruction
 Compression
 Accumulation of fluid, blood or air
 Contraction
 Restrictive –fibrotic changes

9. 9
Acute Lung Injury
 ARDS
 Imbalance of pro- and anti-inflammatory
mediators
 Pathogenesis
 Endothelial or epithelial injury
 Increased vascular permeability
 Alveolar flooding
 Loss of diffusion capacity
 Morphology
 Dark red, firm, airless and heavy lungs
 Presence of hyaline membrane
 Capillary congestion
 Necrosis of alveolar epithelial cells
 Neutrophils in capillary
 Edema fluid
 Pulmonary edema
 Acute Respiratory Distress syndrome (ARDS)

10. 10
Acute Lung Injury
 ARDS Pulmonary edema

11. 11
Diffuse pulmonary diseases
Obstructive diseases Restrictive diseases
 Fibrosing diseases
 Granulomatous diseases
 Pulmonary Eosinophilia
 Smoking related Interstitial
diseases
 Emphysema
 Chronic bronchitis
 Asthma
 Bronchiectasis

12. 12
Obstructive Pulmonary diseases (OPD)
 Almost always chronic (COPD)
 Involves all of the lung compartments – parenchyma, vasculature, and
large and small airways
 Emphysema
 Chronic bronchitis
 Asthma
 Bronchiectasis

13. 13
Emphysema
“Air-containing”/ “inflated”
Morphologically defined
Enlargement of air spaces distal to terminal
bronchi-acinus
1. Centriacinar
2. Panacinar
3. Distal acinar
4. Irregular
 Morphology

14. 14
Emphysema
 Pathogenesis
 Protease –antiprotease imbalance
 Oxidant and antioxidant imbalance
 Clinical course
 Dyspnea
 Cough and wheezing
 Weight loss
 Pink puffers Vs blue bloaters

15. 15
Chronic bronchitis
 Cigarette smokers and urban dwellers in smog-ridden cities
 Pathogenesis
 Hypersecretion of mucus
 Smoke, inhalants, irritants  inflammation
CD8+ T cells, macrophages and neutrophils
 Results from small airway diseases (chronic
bronchiolitis) and coexistent emphysema
 Clinical course
 Persistent productive cough for 3 consecutive
months in 2 consecutive years
 Production of sputum
 Threat: recurrent infection and respiratory failure
 Morphology
 Hyperemic and swollen-edema fluid
 Enlargement of the mucus secreting glands
 Chronic bronchiolitis – goblet cell metaplasia,
mucus plugging, inflammation and fibrosis

16. 16
Asthma
 Chronic inflammatory airway disease-
clinical course:
 Wheezing - bronchospasm
 Breathlessness
 Chest tightness
 Cough
 Hypersensitivity and late-phase
reactions in the lung
 Intermittent and reversible airway
obstruction
 Chronic bronchial inflammation with
eosinophils
 Bronchial smooth muscle cell hypertrophy
and hyper-reactivity
1. Atopic – 70% – allergic
2. Non-atopic – 30% – infection

17. 17
Histological findings in bronchial asthma
1. Inflammation
2. Bronchial narrowing
3. Increase mucous
4. Smooth muscle hyperplasia
• Increased eosinophils associated
with allergy
• Immunologically mediated injury in
the bronchi

18. 18

19. 19
Bronchiectasis
 Permanent dilation of bronchi and bronchioles with chronic necrotizing inflammation
dilatation
 Pathogenesis
 Obstruction clearance is hampered paving way for
infection (e.g. carcinoma)
 Chronic persistence infection – weakening of walls
and dilation
 Morphology
 Affects lower lobes
 Four times dilated in diameter compared to normal
 Intense acute and chronic inflammatory exudate
within the walls of the bronchi and bronchioles
 Mixed flora from involved bronchi
 Clinical course
 Severe, persistence cough
 Expectoration of mucopurulent, fetid
sputum
 Episodic
 Clubbing of fingers

20. 20
Diffuse Interstitial (Restrictive infiltrate) Lung Diseases
 Categorized either as
clinicopathological symptoms or
characteristics histology
 Fibrosing diseases
 Idiopathic pulmonary fibrosis
 Non-specific interstitial fibrosis
 Cryptogenic organizing pneumonia
 Drug reaction
 Radiation changes
 Granulomatous diseases
 Sarcoidosis
 Hypersensitivity
 Pulmonary Eosinophilia
 Smoking related interstitial
diseases
 Pathogenesis
 Morphologically- reduced compliance
 Earliest common manifestation – alveolitis
 accumulation of inflammatory and
immune effector cells within the alveolar
walls and spaces
 Interstitial fibrosis: Activation of
pulmonary macrophages  secretion of
IL-8 and leukotriene B4  recruit and
activate neutrophils
 Oxidants and proteases from neutrophils
leads to lung injury

21. 21
Diffuse interstitial fibrosis
 Restrictive lung diseases –
reduced compliance
 Hetergenous cause of
Fibrosing diseases
 Pathogenic factor
 Injury to the alveoli
 Activated macrophages
 Release of fibrogenic cytokines
 Idiopathic pulmonary fibrosis
–prototype
 Patchy lung fibrosis
 Formation of cystic spaces

22. 22
Idiopathic pulmonary fibrosis (IPF)
 Pattern of fibrosis - Usual interstitial
pneumonia (UIP)
 Idiopathic – unknown etiology
 Diffuse interstitial fibrosis
 Hypoxemia and cyanosis
 Morphology
 Pleural surface appears as cobblestones
–scar retraction
 Fibrosis – firm, rubbery white areas
 Clinical course
 Nonproductive cough and dyspnea
 Dry and Velcro like crackles during inspiration

23. 23
Fibrosing diseases
Nonspecific Interstitial pneumonia Cryptogenic organizing pneumonia
 Wastebasket diagnosis
 Types
 Cellular patterns
 Fibrosing patterns
 Pattern consists of diffuse or patchy
interstitial fibrosis
 Fibroblastic foci are absent
 Bronchiolitis obliterans – idiopathic
 Radiograph- Subpleural patchy areas of
airspace consolidation
 Alveolar ducts – filled with balls of
fibroblasts

24. 24
Pneumoconiosis
 Lung reaction to inhalation of mineral dusts
 Occupational diseases
 Coal workers’ pneumoconiosis- exposure to coal dust
 Silicosis – exposure to silica
 Asbestosis and asbestos-related diseases – exposure to asbestos Copyright © 2015 richardalois.com
 Clinical course
 Pulmonary dysfunction
 Hypertension

25. 25
Granulomatous diseases
 Granulomas involves the interstitium rather than airspaces
 Localize around connective tissue of the bronchioles and pulmonary
venules and in the pleura
 Progresses to diffuse interstitial fibrosis
 Sarcoidosis –non-caseating granulomas -idiopathic
 Hypersensitivity Pneumonitis (dusts, bacteria, fungi, farmer’s lung,
Pigeon breeder’s lung)

26. 26
Sarcoidosis
 Mainly lungs, but eye, skin or anywhere
 Unknown etiology - Immune, genetic
factors
 Pathogenesis
 Cell mediated response to unidentified antigen
 Intra-alveolar and interstitial accumulation of CD4+ TH1
cells
 Increases in T cell derived cytokines – IL-2 and IFN-y 
macrophage activation
 Increase in IL-8, TNF  contribute to the formation of
granulomas
 Antigens – viruses, mycobacteria, pollen
Epithelioid cells
Lymphocytes CD4+ T cells
fibroblasts
Non-caseating granulomas is the rule
Asteroid bodies Schaumann bodies

27. 27
Caseating granuloma –
Tuberculosis
Non-caseating granuloma -
Sarcoidosis

28. 28
Hypersensitivity Pneumonitis
 Immunologically mediated
inflammatory disease
 Affects alveoli – allergic
alveolitis
 Morphology
 Patchy mononuclear cell infiltrates
in the interstitium
 Lymphocytes dominate, presence of
plasma cells and epithelioid cells
 Interstitial non-caseating
granulomas are present

29. 29
Pulmonary Eosinophilia
 Infiltration and activation of eosinophils – elevated levels of alveolar
IL-5
 Incompletely understood
 Acute eosinophilic pneumonia with respiratory failure
 Simple pulmonary eosinophilia
 Tropical eosinophilia – infection with parasite – microfilaria
 Secondary eosinophilia – in asthma and allergies
 Idiopathic chronic eosinophilic pneumonia

30. 30
Smoking related Interstitial Diseases
 Cigarette  obstructive disease –
emphysema and chronic
bronchitis
 But also restrictive or interstitial
diseases
 Desquamative interstitial
pneumonia (DIP)
 Accumulation of large number of
macrophages with cytoplasm having
dusty brown pigment (smokers’
macrophage) in the airspaces
Accumulation of mononuclear cells within alveolar spaces and mild
thickening of alveolar walls

31. 31
Diseases of Vascular origin
 Pulmonary embolism, Hemorrhage, and infarction
 Pulmonary hypertension
 Diffuse alveolar hemorrhage syndromes
 Goodpasture syndrome
 Idiopathic pulmonary hemosiderosis
 Pulmonary angiitis and granulomatosis

32. 32
Pulmonary embolism (PE)
 Blood clot(s) migrate from the systemic
circulation to the pulmonary vasculature.
 Deep veins of the lower and upper extremities (deep venous
thrombosis [DVT]
 Morphology
 Size of the embolic mass
 General state of circulation
 Saddle embolus – pulmonary arteries
Stasis Immobility
Bed rest
Anesthesia
Congestive heart failure/cor pulmonale
Prior venous thrombosis
Hypercoagulability Malignancy
Anticardiolipin antibody
Nephrotic syndrome
Essential thrombocytosis
Estrogen therapy
Heparin-induced thrombocytopenia
Inflammatory bowel disease
Paroxysmal nocturnal hemoglobinuria
Disseminated intravascular coagulation
Protein C and S deficiencies
Antithrombin III deficiency
Vessel wall injury Trauma
Surgery
Large saddle embolus
from the femoral vein-
impacted in the main left
and right pulmonary
arteries

33. 33
Pulmonary hypertension
 Chronic obstructive or interstitial lung disease
 Recurrent pulmonary emboli
 Antecedent heart disease
 Pathogenesis
 Pulmonary endothelial cell and/or vascular smooth muscle
dysfuntion
 TGF-B signaling pathway
 Shear and mechanical injury
 Morphology
 Main elastic arteries
 Medium sized muscular arteries
 Smaller arteries and arterioles
Medial hypertrophy
Plexogenic lesion

34. 34
VERY thickened
arteriole in pulmonary
hypertension
NORMAL pulmonary arteriole
Narrowing causes HTN, and HTN causes narrowing! (vicious cycle)

35. 35
Hemorrhagic syndromes
 Primary immune mediated
diseases – triad of hemoptysis,
anemia and diffuse pulmonary
infiltrates
 Goodpasture syndrome – Abs to
the alpha-3-chains of collagen IV
 Idiopathic pulmonary
hemosiderosis
 Wegener Granulomatosis
 Pulmonary angiitis and granulomatosis
 Iron stain shows abundant
intracellular hemosiderin

36. 36
Pulmonary infections - Pneumonia
 Epithelial surface constantly exposed to variously contaminated air
 Nasopharyngeal flora are aspirated regularly during sleep
 Common lung diseases render parenchyma vulnerable to virulent
organisms
 Innate immunity and acquired immunity in the respiratory system

37. 37
Lung defense mechanism

38. 38
Pulmonary infections
 Community acquired acute pneumonia
 Community acquired atypical pneumonias
 Nosocomial pneumonia
 Aspiration pneumonia
 Lung abscess
 Chronic pneumonia
 Pneumonia in the immunocompromised host
 Opportunistic fungal infection
 Pulmonary infection in HIV infection

39. 39
Community Acquired Acute Pneumonias
 Bacterial origin
 Infection follows viral upper respiratory tract infection
 High fever
 Shaking chills
 Pleuritic chest pain
 Productive mucopurulent cough
 Most common – Streptococcus pneumoniae

40. 40
Types: Bronchopneumonia and Lobar pneumonia
Bronchopneumonia Lobar pneumonia
 Patchy distribution of neutrophilic
infiltrate and bacterial organisms in one
or many lobes
 Causative organisms: Many,
including Streptococcus
pneumoniae and Klebsiella pneumoniae.
 conditions that predispose
 Loss of the cough reflex,
 injury to the mucociliary escalator,
 dysfunction of alveolar macrophages,
pulmonary edema and congestion,
 accumulation of secretions.
 Pneumonia confined to one lobe of the
lung
 Causative organisms: Almost all cases
are due to Streptococcus pneumoniae.
 Morphologic stages of lobar
pneumonia in order of development
 Edema and congestion.
 Red hepatization: Lobe is red and
firm, and alveoli are filled with
neutrophils, fibrin, and red blood
cells.
 Grey hepatization: Red blood cells
have lysed; fibrin and macrophages
remain.
 Resolution.

41. 41
Streptococcus pneumoniae
 Occurs in individuals with
 Chronic diseases (CHF, COPD or diabetes)
 Congenital or acquired immunoglobulin defects (AIDS)
 Decreased or absent splenic function (sickle cell disease) (spleen contains phagocytes that are
important for pneumococci removal from the blood)
 Morphology
 Lobar or bronchopneumonia
 20% adults harbor in pharyngeal flora
 Stages: congestion, red hepatization, gray hepatization and resolution
 Vaccination -100%preventive
 Penicillin -100% curative (early detection)

42. 42
Haemophilus influenzae
 Encapsulated and unencapsulated
 Life threatening in children that can lead to respiratory viral infection
 Adults- chronic pulmonary diseases – chronic bronchitis,
bronchiectasis
 Cause of Epiglottis and Meningitis in children
 Vaccination reduces the risk

43. 43
Staphylococcus aureus
 Most common pneumonia following viral pneumonia (measles and
influenza)
 Associated with high incidence of complication such as Lung abscess
and empyema

44. 44
Klebsiella pneumoniae
 Debilitated malnourished people
 ALCOHOLICS with pneumonia are often thought of as
having Klebsiella until proven otherwise

45. 45
Pseudomonas aeruginosa
 Usually NOT community acquired but nosocomial
 CYSTIC FIBROSIS patients with pneumonia are presumed
to have PSEUDOMONAS until proven otherwise

46. 46
Legionella pneumophila
 Often in OUTBREAKS
 Often LOBAR
 Spread by water “droplets”

47. 47
Community Acquired Atypical Pneumonias
 Viral (influenza)
 Mycoplasma (mycoplasma pneumoniae (obligate intracellular))
 Not bacterial
 Cultures not helpful; requires PCR for mycoplasma
Viral pneumonias, generally interstitial, bacterial pneumonias generally alveolar!!!

48. 48
Influenza virus
 Single stranded RNA virus bound by nucleoprotein – virus
type (A, B or C)
 Spherical surface contains hemagglutinin and
neuramidinase – H1N1
 Type A – pandemic and epidemic
 Mutations allow virus to escape host antibodies

49. 49
SARS (Severe Acute Respiratry Syndrome)
 CORONA-VIRUS
 2002 China outbreak
 Spread CHIEFLY in Asia
 Like most other NON-bacterial pneumonias confirmed by PCR
 Like most viral pneumonias, interstitium infiltrated, some giant
cells often present

50. 50
Nosocomial Pneumonia – hospital acquired
 Risk to patients with
 Severe underlying disease
 Immune suppression
 Prolonged antibiotic therapy
 On mechanical ventilation – ventilator associated pneumonia
 Common isolates
 Gram-negative rods (Enterobacteriacea and Pseudomonas spp.)
 S.aureus (MRSA)
 MRSA (MR=Methicillin Resistant)

51. 51
Aspiration Pneumonia
 Debilitated patients
 Aspirate gastric contents while unconscious
 During repeated vomiting
 Result of the gastric acid, partly chemical and partly bacterial
 Lack of ability to swallow
 Leads to lung abscess
 Aerobes and anaerobes

52. 52
Lung Abscess – complication of pneumonia
 Causative organism introduced in
the lung by
 Aspiration of infective material –oral surgery,
anesthesia or alcoholic intoxication
 Aspiration of gastric contents
 Necrotizing bacterial pneumonia
 Bronchial obstruction
 Septic embolism
 normal lung outline can no longer be
seen
 100% pus
 destruction of the alveolar

53. 53
Chronic Pneumonia
 Granulomatous inflammation due to bacteria or fungi
 Tuberculosis – primary and secondary
 Histoplasmosis
 Coccidioidomycosis
 Blastomycosis
 Pulmonary granulomas – think of chronic process often in years

54. 54
Tuberculosis (TB)
 Chronic granulomatous disease caused by Mycobacterium tuberculosis
 Pathogenesis
 Initial exposure – immune response confers resistance but also leads to hypersensitivity
 Positive tuberlin test
 CD4+T cells of TH1 subset against mycobacterium
 Granulomas – central caseating necrosis
 Reactivation in previously exposed individuals
Primary tuberculosis
Secondary tuberculosis

55. 55
Natural history and spectrum of tuberculosis

56. 56
Histoplasmosis, Coccidioidomycosis and Blastomycosis
 Dimorphic fungi
 Histoplasma capsulatum, Coccidioides immitis and Blastomyces dermatitidis
 Warm moist soil, enriched by droppings from bats and birds-infectious spores
 Tiny organism live in macrophages
 Can affect many other organs
Histoplasmosis Coccicioidomycosis Blastomycosis

57. 57
Pneumonia in the immunocompromised host
 Immuncompromise or immune suppression
 Organ transplants
 Tumors
 Disease
 Opportunistic agents
 Bacteria
 Viruses
 Fungi
 Cytomegalovirus Infections
 Affects lungs, GI tract and retina
 Lungs- necrosis, enlarged inclusions
 Pneumocystis Pneumonia -fungi
 Formerly P.carinii but now P.jirovecii

58. 58
Lung tumors – Carcinoma of the Lung – Lung cancer
Cancer Registry of Norway. Cancer in Norway 2016 - Cancer incidence, mortality, survival and prevalence in
Norway. Oslo: Cancer Registry of Norway, 2017

59. 59
Type of Lung Carcinomas

60. 60
Bronchial Carcinoids
 Arise from Kulchitsky
cells (neuroendocrine
cells)
 Lines the brochial mucosa
 Resemble intestinal
carcinoids
 Resectable and curable
 Morphology
 Obstructing polypoid, spherical, intraluminal mass
 Mucosal plaque penetrating the bronchial wall protruding
peribronchial tissue
 Regular round nuclei, rounded cells

61. 61
TNM classification : Lung tumor

62. 62
Pleural Lesions
 Pleural effusion
 Pleuritis
 Pneumothorax – air in pleural cavity
 Hemothorax – blood in pleural cavity
 Chylothorax – milky lymphatic fluid – microglobules of lipids
 Malignant Mesothelioma

63. 63
Pleural effusion and Pleuritis
 Fluid in pleural space
 Transudate: Serous fluid; often due to left-sided heart failure. (hydrothorax)
 Exudate: Most commonly due to pulmonary infections, carcinoma, infarction, or viral pleuritis;
occasionally due to connective tissue disorders and uremia.
 Exudates have: specific gravity > 1.016; pleural fluid protein of > 3.0
gm/dL
 Clinical presentation of pleural effusions
 Symptoms: Dyspnea; sharp chest pain due to involvement of the parietal pleura that is worsened
by coughing or breathing; or dull chest pain due to involvement of the visceral pleura; or dry
cough due to irritation of the pleural surfaces.
 Diagnosis of pleural effusion: Confirmed by physical examination and
chest radiograph.

64. 64
Pneumothorax
 Air within a pleural cavity.
 Types
 Tension pneumothorax: Defect in the pleura acts as a one-way valve. Air enters the pleural cavity with
inspiration but cannot leave it (ball-valve mechanism).
 Nontension pneumothorax: Air trapped in the pleural cavity; clinical consequences depend upon size;
 Two types of pneumothorax (by etiology)
 Spontaneous
 Traumatic
 Symptoms
 Sudden onset of sharp chest pain
 worsened by inspiration
 tachypnea
 With a tension pneumothorax, patients also have hypotension and cyanosis.
 Signs:
 Hyperresonance to percussion,
 decreased tactile fremitus, and
 decreased breath sounds over the affected area.
 With a tension pneumothorax, patients will have elevated jugular venous pressure.

65. 65
Mesothelioma
 Benign or malignant
 Occupational exposure
 Asbestos (shipyard workers, miners, insulators)
 Combination of cigarette smoking and asbestos exposure increases
risk
 Malignant
 Pleural fibrosis and plaque formation (CT scans)
 Yellow-white, firm gelatinous layer of tumor at autopsy
 Histological observations
 Epithelial –small papillary buds project
 Sarcomatoid –spindled fibroblastic appearance
 Biphasic- both sarcomatoid and epithelioid

66. 66
References