1a. The Lung.pdf 2.pdfhhhhhhhhhhhhhhhhhhh

Anapath

1. The LUNG
The airways ,
The interstitium,
The pulmonary vascular system

2. Diagrammatic
•Endothelium and basement membrane
•Interstitium–fine elastic fibers,
•Small bundles of collagen
•Fibroblast like cell
•Smooth muscle cells
•Mast cells
•Rare mononuclear cells
•Alveolar epithelium
•Type 1 pneumocytes
•Type II pneumocytes
•Few macrophages lie free in the alveolar
space The airways

3. ATELACTASIS
Atelectasis (collapse)
•Loss of lung volume caused by inadequate
expansion of air spaces.
•Result into shunting of inadequate oxygenated
blood from pulmonary arteries into vein
Ventilation perfusion imbalance
•Loss of lung volume caused by inadequate
expansion of air spaces.
Classification
•Underlying mechanism and distribution of alveolar
collapse.
1.Resorption
2.Compression
3.Contraction

4. Acute Respiratory Distress Syndrome
•Acute respiratory distress syndrome
•Not to be confused by ARDS of newborn.
•Respiratory failure occurring 1 week of a known clinical insult
•with bilateral opacities on chest imaging , not fully explained by
effusions, atelectasis, cardiac failure, or fluid overload.
•Graded according to severity of the changes in arterial blood
oxygenation.
•Causes are diverse –
•All lead to bilateral injury of the alveoli.

5. ARDS
•Characterized by :
-respiratory insufficiency
-cyanosis
-severe arterial hypoxemia that is refractory to oxygen therapy

6. Causes of ARDS
•Primary respiratory diseases
•Severe systemic sepsis
•Aspiration
•Trauma
•Pancreatitis
•Transfusion reactions

7. Pathogenesis
•Local tissue damage
•Accumulation of edema fluid
•surfactant inactivation
•Hyaline membrane formation
•Subsequently the release of macrophage derived fibrogeniccytokines
(i.e. TGF-B, PGDF )
•Stimulation of fibroblast growth
•Collagen deposition associated with healing phase of injury

8. PATHOGENESIS
•Endothelial and epithelial injury
•Pro-inflammatory cytokines
released by macrophages
•Endothelial activation
•Sequestration of neutrophils into
alveolar capillaries
•Activated and release
leukotrienes, oxidants, proteases
and platelet activation factor

9. Pathogenesis

•Can be counteracted by array of endogenous anti-proteases and
antioxidants
•Upregulated by pro-inflammatory cytokines
•The balance between the destructive and protective factors
•Determines the degree of tissue injury
•Clinical severity
• The destructive forces unleased by neutrophils

10. Histology
•Diffuse alveolar damage
•Some alveoli are collapsed
•Other are distended
•Line by bright pink
(eosinophilic)hyaline membrane

11. Clinical features
•85% of cases develops within 72 hours of initial insult
•Overall hospital mortality rate 38,5 %
•Predictors of poor prognosis include:
-Advance age
-Bacteremia (sepsis)
-Developments of multi organ failure

12. Obstructive vs Restrictive pulmonary disease
OBSTRUCTIVE :
•Increased resistance to airflow
•Partial or complete obstruction at any level
•Forced vital capacity is either normal or slightly decrease
•Expiratory flow rate(measured as forced expiratory volume at 1
second FEV1) is significantly decrease
•Ratio FEV to FVC is charactisticallydecrease

13. Restrictive
•Characterize by reduce expansion of lung parenchyma
•Decrease total lung capacity
•May result from anatomic airway narrowing obstruction –asthma
•Loss of elastic recoil –emphysema
•FVC is reduced and FEV1 normal or reduced
•Hence the ratio FEV to FVC is near normal

14. Restrictive
chest wall disorders in the presence of normal conditions
•Severe obesity
•Disease of the pleura
•Neuro muscular disorders acute and chronic interstitial lung diseases
•ARDS
•Pneumoconiosis
•Interstitial fibrosis of unknown etiology
•Infiltrative conditions like sarcoidosis

15. Obstructive / COPD
•Emphysema
•Chronic bronchitis
•Asthma
•Bronchiectasis

16. Emphysema
•Characterized by permanent enlargement of airspaces distal to the
terminal bronchioles
•Accompanied by destruction of the walls without significance
fibrosis.
Classification–According to the anatomic distribution
•Centriacinarx 20 more common
•Panacinar
•Distal acinar
•Irregular

17. Emphysema

18. Emphysema

19. Pathogenesis
•Inflammatory cells and mediators
•Protease anti-protease imbalances
•Oxidative stress
•Airway infections

20. Protease anti protease imbalances
•The observed that patient with genetic deficient of the anti protease
•Compounded by smoking
•a1 –antitrypsin normally present in tissue fluids and macrophages, is
a major inhibitor of protease
•Particularly elastase secreted by neutrophils during inflammation
•Protease-mediated damage of extracellular matrix has a central role
in the airway obstruction seen in emphysema.

21. Pathogenesis of emphysema

22. Clinical features
•Dyspnea –steadily progressive
•Weight loss
•Recurrent infections
•In the absence of increased respiratory drive –retains co2
•Hypoxia and cyanosis

23. Conditions related to emphysema
•Compensatory –dilation of residual alveoli in compensation of loss of
parenchyma
•Obstructive over inflation –expansion of the lung due to air trapping
•Bullous emphysema –subpleuralblebs
•Mediastinal/ interstitial emphysema –entry of air into the
mediastinum

24. Chronic bronchitis
Clinical diagnosis
•Characterized by the presence of persistent productive cough
•At least 3 consecutive months
•At least 2 consecutive years

25. Bronchiectasis
•Permanent dilation of bronchi and bronchioles
•Caused by destruction of smooth muscle and supporting elastic
tissues
•Typically results from or associated with chronic necrotizing infections

26. Bronchiectasis
predisposing conditions
•Bronchial obstruction: -tumors, foreign bodies, impaction of mucus
•Congenital or hereditary conditions :
-cystic fibrosis –obstruction caused by abnormal viscid mucus and
secondary infections.
•Immunodeficiency states
•Primary ciliary dyskinesia (immotile cilia syndrome)
•Necrotizing or suppurativepneumonia

27. Clinical features
•Severe persistent cough associated with expectoration of
mucopurulent sputum
•Dyspnea
•Rhinosinusitis
•Hemoptysis

28. Asthma
•Chronic inflammatory disorder of airways
•Characterized by narrowing of airways
•Increased mucus production
•Hyper responsive to variety of stimuli
•Intermittent and reversible
•Atopic and non-atopic

29. Asthma
Diverse exposure
•Respiratory infections
•Airborne irritants
•Cold air
•Stress
•Exercise

30. Atopic asthma
•Most common
•Evidence of allergen sensitization
•Usually begins in childhood
•Positive family history
•Attack often preceded by allergic rhinitis, urticarial or eczema
•IgE-mediated hyper-sensentivityreaction

31. Asthma
•Triggered by allergen
•Th2 cell activation
•Production of cytokines IL-4 and
IL-13
•Stimulate IgEproduction
•IL5 activates eosinophils
•IL-13 stimulates mucus
production
•IgEcoats submucosal mast cells

32. Asthma
•Exposure to allergen triggers the
release of mast cell granules
•Secretion of cytokines and other
mediators
•Mast cells derived mediators
produce two waves of reaction
•Early /immediate reaction
•Late phase

33. Early phase
•Histamine, PGD2 and Leukotrienes
•Increased mucus production
•vasodilation and edema
Late Phase
•Inflammatory mediators stimulate epithelial to prducechemokines
•Recruitment of Th2
•Eosinophils

34. Asthma
•Repeated bouts of inflammation lead to structural changes –airway
remodeling
•Hypertrophy of bronchial smooth muscle and mucus glands
•Increased vascularity and deposition of subepithelialcollagen

35. Types of asthma
•Drug induced
•Occupational
Clinical features
•Wheezing
•Dyspnea
•Mucus plugging

36. Restrictive disease
•Chronic interstitial disease are a heterogeneous group of disorders
characterized by bilateral, often patchy pulmonary fibrosis mainly
affecting the walls of the alveoli

37. Pneumoconiosis

38. Pulmonary disease of vascular origin
pulmonary embolism
•95% arise from thrombus –DVT
Risk factors
•Prolonged bed rest ( immobilization)
•Surgery
•Severe trauma with multiple burns and fractures
•Congestive heart failure
•High estrogen/ unopposed estrogen
•Disseminated cancer
•Hypercoagulability state/ increased viscosity

39. Pulmonary embolism
•Size of the vessel involved
•Cardiopulmonary status of the
patient
•Saddle embolus embed in the
main pulmonary artery or major
branches or at the bifurcation
•Common cause of common
death
•Acute hypoxia or acute failure of
the right side of the heart

40. Pulmonary embolism
•Compromised cardiovascular status
•Infarction occurs
•Adjacent pleura covered by fibrinopurulent
exudate
•Acute life threatening thrombo-embolism is
reported in covid19 patients
•Significant procoagulantevents

41. Lung infarct

42. Clinical features
•60% to 80% are asymptomatic –small
•5% death ,acute right sided failure
•Shock
•Dyspnea following infarct
•<3% Pulmonary hypertension following recurrent small “showers”

43. Pulmonary hypertension
•1/8 systemic pressure
•Pressure of 25mmHg or more at rest
•May be caused by decrease in the cross-sectional area of the
pulmonary vascular bed
•Increased pulmonary vascular flow

44. Morphology
•Medial hypertrophy of the
pulmonary muscular and elastic
arteries
•Pulmonary arterial
atherosclerosis
•Right ventricular hypertrophy

45. Pulmonary hypertension

46. Clinical features
•Idiopathic common in women 20 to 40 years
•Dyspnea and fatigue
•Anginalchest pain
•Respiratory distress
•Cyanosis
•Right ventricular hypertrophy/ cor-pulmonale

47. •Two patterns of anatomic
distribution
•Broncho-pneumonia and Lobar
pneumonia
Bacterial pneumonia
Pneumonia

48. Pathology

49. Lobar vs broncho pneumonia

50. Morphology

51. Complications

52. Tuberculosis ( chronic pneumonia)
•Communicable chronic granulomatous disease caused by
Mycobacterium tuberculosis
•Flourishes under conditions of poverty, crowding, and chronic
debilitating illness.

53. Tuberculosis
Increased risk
•Diabetes mellitus
•Hodgkin's lymphoma
•chronic lung disease
•Chronic renal failure
•Malnutrition
•Alcoholism
•Immunosuppression

54. Tuberculosis
•Lowered immune system may activate to produce communicable and
potentially life threatening disease
•Infection with M.tuberculosiscan be detected 2 to 4 weeks after
infection by tuberculin (Mantoux) test

55. Tuberculosis
Transmission :
•Direct to direct
•Airborne droplets of organism from an active case to a susceptible
host.
•Asymptomatic focus of pulmonary infection that is self limited
•Primary tuberculosis may result in the development of fever and
pleura effusions
•The only evidence may be a tiny fibrocalcificnodule at the site of
infection
•Viable organism may remain dormant

56. Primary tuberculosis
•Previously unexposed, unsensetizedindividuals
•Reactivation leads to progressive primary tuberculosis
•Immunosuppression results in ability to mount a CD4+ T cell-
mediated response that would contain the primary focus
•Lack of a tissue hypersensitivity reaction results in he absence of the
characteristic caseatinggranulomas

57. Morphology primary tuberculosis
•Grey white parenchymal focus
under the pleura in the lower
part of the upper lobe
•May also be found on the upper
part of the lower lobe Ghon
focus
•Travel via lymphatic to hilar
lymph nodes with caseation are
seen. Ghoncomplex
•Progressive fibrosis and
calcification Ranke complex

58. Primary tuberculosis

59. Secondary tuberculosis
•Previously sensitized
•Commonly arise from activation of dormant foci
•May also arise from reinfection
•Localized at the apex-

60. Secondary tuberculosis
•Severe immunocompromised
•Progressive primary tuberculosis
•Non cavitatory, lower and middle lobe , hilar lymphadenopathy
•Fibro-cavitatoryform –erosion via the airways
•Infectivity production of sputum containing bacilli

61. Secondary tuberculosis
Miliarytuberculosis
•Extension and dissemination through airways, lymphatic channels and
blood stream –miliarytuberculosis
•Pleural extension includes : effusions, empyema obliterativefibrous
pleuritic
•Systemic miliarytuberculosis
•When the vertebrae are involved –Pott disease
•Disseminated tuberculosis

62. Secondary tuberculosis

63. Histology of necrotizing granuloma

64. Lung tumors
•95% of lung tumors are carcinomas
•Most important cause of cancer-related deaths in industrial countries
•50 years to 60 years
•Smoking related carcinomas of lung arise by a stepwise accumulation
of driver mutations
•Transformation of benign progenitor cells
•Neoplastic cells possessing all of the hallmarks of cancer
•Cigarette smoking and environmental carcinogens main culprits
•Commonly cause a variety of paraneoplastic syndrome

65. Histologic classification
•Adenocarcinoma –(common in non-smokers)
•Squamous cell carcinoma
•Large cell carcinoma
•Neuroendocrine carcinoma
-small cell carcinoma
-large cell neuroendocrine carcinoma
-carcinoid tumor
•Mixed carcinomas
•Others

66. Lung tumor gross

67. Pleural lesions
•Hydrothorax –transudate
•Pleural exudate –empyema, cancer, mesothelioma, metastasis,
infarctions, viral pleuritic
•Pneumothorax –air or gas in the pleural sac
•Hemothorax–collection of whole blood
•Chylothorax–collection of milky lymphatic fluid containing
microglobules

68. Lesion of the upper respiratory tract
•Acute infections –
Nasopharyngeal tumors
•-strong epidemiology link to EBV
•EBV genome found in almost all nasopharyngeal carcinoma
•Burkittlymphoma another EBV associated tumor
Histologic types of nasopharyngeal tumors
•Keratinizing squamous cell carcinoma
•Non-keratinizing squamous cell carcinoma
•Undifferentiated carcinoma

69. Laryngeal tumors
•Most common presenting features hoarseness of voice
Non-malignant vocal cords nodules (polyps)–
•Smooth, hemispherical protrusions ( usually <0.5cmin diameter)
•Located most often in true vocal cords
•Consist of fibrous tissue covered by stratified squamous mucosa
•Often ulcerated following chronic irritation
•Common in smokers and singers (singers nodes)

70. Laryngeal papilloma /squamous papilloma
•Located on the true vocal cords
•Soft raspberry like excrescence
•Rarely 1cm in diameter
•Usually single in adults
•Multiple in children
•Caused by HPV types 6 and 11
•Spontaneous regression at puberty
•Cancerous transformation is rare

71. Morphology
•Multiple slender fingerlike projections supported by central vascular
core
•Covered by unremarkable stratified squamous epithelium.
•May undergo surface ulceration that can be accompanied by
hemoptysis

72. Laryngeal papilloma

73. Carcinoma of the larynx
•Common after 40 years of age
•Men than women
•Occur in smokers alcohol and asbestos exposure may play a role
•HPV have been detected in 15% of cases
•95% are squamous cell carcinoma
•Rarely adenocarcinoma
•Plaque, ulcerating or fungating

74. Laryngeal carcinoma