Respiratory system


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Respiratory system

  2. 2. • Respiratory diseases, particularly lung infections,cause most damage in developing countries where,together with gastrointestinal infections, theyaccount for a heavy morbidity and mortality.•Most respiratory illnesses are due toenvironmental factors, especially smoking
  3. 3. Aetiological Factors in Respiratory Disease ___________________________________________________________________________ Aetiological Factors Disease ___________________________________________________________________________ Genetic Cystic Fibrosis α 1 – Antitrypsin deficiency Some types of Asthma___________________________________________________________________________Environmental Smoking Lung cancer Chronic Bronchitis and Emphysema Susceptibility to infection Air pollution Chronic Bronchitis Susceptibility to infection Occupation Pneumoconiosis Asbestosis Mesothelioma Lung Cancer Infection Influenza Measles Bacterial Pneumonias Tuberculosis___________________________________________________________________________
  4. 4. Normal Structure and Function•The respiratory system extends from the nasal orifices to the peripheryof the lung and the surrounding pleural cavity.• From the nose to the distal bronchi , the mucosa is lined by mainlypseudo stratified ciliated columnar epithelium with mucus – secretinggoblet cells; this is Respiratory Mucosa .• The co – ordinated rhythmic breathing of the cilia in the surface of therespiratory mucosa wafts mucus containing dust particles from thedepths of the lung up to the larynx. From there the mucus can be eitherexpectorated or swallowed
  5. 5. Histology of the respiratory epithelium:Anatomy of the respiratory system With the exception of pharynx, epiglottis and vocal cards , the respiratory tract is lined by specialized ciliated mucus-secreting epithelium
  6. 6. • The lungs are divided into lobes; the right lung has three lobes ( upper, middle, lower); the left lung has only two lobes ( upper andlower) . Each lung is formed of ten anatomically defined BronchopulomnarySegments. Each segment is supplied by a segmental artery and a branch , butthe veins draining adjacent segments often anastomose before they reach thehilum.• The Lower Respiratory Tract consists of the trachea, bronchi, bronchioles,alveolar duct and alveoli. The structure of each portion differs.• The respiratory tree is designed to transport clean, humidified air intodistal airways and alveoli, where the waste product of metabolism (CO 2 ) isexchanged for O2 .
  7. 7. Structure and nomenclature of lower respiratory tract
  8. 8. Structure of the Respiratory Tree _________________________________________________ Part of Respiratory Tract Structure_________________________________________________ Trachea Anterior C- shaped plates of cartilage with posterior smooth muscle . Mucous glands_____________________________________________________________ Bronchi Discontinuous foci of cartilage with smooth muscle . Mucous gland_____________________________________________________________Bronchioles No cartilage or submucosal mucous glands. Clara cells secreting proteinoaceous fluid . Ciliated epithelium._____________________________________________________________ Alveolar Duct Flat epithelium. No glands. No cilia_____________________________________________________________Alveoli Type I and II pneumocytes_____________________________________________________________
  9. 9. Obstructive VsRestrictive Lung Diseases
  10. 10. Obstructive VS restrictive Lung DiseaseObstructive Lung Disease Restrictive Lung DiseaseCharacterized by limitation of Characterized by reducedairflow usually resulting from expansion of lung parenchymapartial or complete obstruction at accompanied by decreased totalany level lung capacityNormal or increased total lung Decreased total lung capacity andcapacity and forced vital Forced Vital Capacity(FVC)capacity(FVC)Decreased Forced Expiratory Forced Expiratory Volume (FEV) isVolume(FEV) is the hallmark normalRatio of FEV to FVC is Ratio of FEV to FVC is near normalcharacteristically decreased
  11. 11. Obstructive VS restrictive Lung DiseaseExamples of obstructive lung Examples of restrictive lung diseases diseases1. Emphysema a. Chest wall disorders in the2. Chronic Bronchitis presence of normal lung: Severe obesity; Diseases of3. Bronchiactasis pleura; Neuromuscular4. Asthma disorders b. Acute or Chronic restrictive diseases (i) Acute restrictive disease : Acute Respiratory Distress Syndrome (ARDS) (ii) Chronic restrictive disease: Pneumoconiosis; Interstitial Fibrosis ; Sarcoidosis
  12. 12. CHRONIC OBSTRUCTIVE PULMONARY DISEASE•The term Chronic Obstructive Pulmonary Disease (COPD) refers toa group of conditions that share a major symptom - Dyspnoea -and are accompanied by chronic or recurrent obstruction to airflowwithin the lung.• The diseases included in COPD are: (i) Chronic Bronchitis (ii) Bronchiactasis (iii) Asthma (iv) Emphysema (v) Small Airway Disease ( Bronchiolotis)
  13. 13. DISORDERS ASSOCIATED WITH AIRFLOW OBSTRUCTION : THE SPECTRUM OF CHRONIC OBSTRUCTIVE PULMONARY DISEASECLINICAL ANATOMIC MAJOR ETIOLOGY SIGNS/SYMPTOTERM SITE PATHOLOGIC MS CHANGESChronic Bronchus Mucous gland Tobacco Smoke; Cough; SputumBronchitis hyperplasia, Air Pollutants production hypersecretionBronchiactasis Bronchus Airway dilation Persistent or Cough; purulent and scarring severe infections sputum; FeverAsthma Bronchus Smooth Muscle Immunologic or Episodic hyperplasia, undefined causes wheezing, Cough, excess mucus, Dyspnoea InflammationEmphysema Acinus Airspace Tobacco smoke Dyspnoea enlargement; Wall destructionSmall airway Bronchiole Inflammatory Tobacco smoke, Cough ;disease scarring ; air pollutants, Dyspnoea(Bronchiolotis) Obliteration miscellaneous
  14. 14. EMPHYSEMA•Emphysema is a condition of lung characterized byabnormal permanent enlargement of the airspaces distal tothe terminal bronchioles, accompanied by destruction oftheir walls, and without obvious fibrosis•Acinus: Acinus is the part of lung distal to terminalbronchiole and includes respiratory bronchiole, alveolarduct and alveoli; a cluster of three to five acini is referred toas a lobule•TYPES OF EMPHYSEMA: Emphysema is defined in terms of theanatomic nature of the lesion, and it can be further classified accordingto its anatomic distribution within lobule.• Although the term emphysema is sometimes loosely applied todiverse conditions, there are four major types: (i) Centriacinar (ii) Panacinar (iii) Paraspetal (iv) irregular
  15. 15. Classification of Emphysema: Emphysema is classified according tothe pattern of distribution of lesions. These can be correlated withspecific aetiological factors to some extent, e.g., centrilobularemphysema and cigarette smoking
  16. 16. TYPES OF OCCURS LOCATION CAUSEEMPHYSEMA1. Centri - Acinar In central or In upper lobes Cigarette smoking (Centri – Lobular) proximal part of the especially apical acini, formed by segments respiratory bronchiole2. Pan – Acinar In acini from In lower lung lobes Alpha1- Antitrypsin(Pan – lobular) respiratory deficiency bronchiole upto terminal blind alveoli3. Distal – Acinar In distal part of the Severe in upper Adjacent to areas of(Para – septal) acini, formed by half of the lung fibrosis, scarring or alveolar ducts and usually adjacent to atelactasis alveoli pleura4. Irregular Acini are Adjacent to areas Healed irregularly enlarged of scarring . inflammatory and destroyed process e.g., Tuberculosis
  17. 17. Bullous Emphysema: This is not a separate category of emphysema.Itrefers to the presence of balloon – like foci of emphysema over 10 mm indiameter. Cases of emphysema with bullae should, where possible, beclassified into one of the four anatomical types. Bullae are prone torupture, causing Spontaneous Pneumothorax
  18. 18. PATHOGENESIS OF EMPHYSEMA•Current hypothesis favours Emphysema arising as aconsequence of two critical imbalances: (i) Protease- Antiprotease Imbalance (ii) Oxidant – Antioxidant Imbalance1. Protease – Antiprotease Mechanism •The protease – Antiprotease theory holds that alveolar walldestruction results from an imbalance between Proteases ( mainlyElastase) and Antiprotease .So increased Protease and decreasedAntiprotease or antielastase like α 1 – Antitrypsin leads to Emphysema. •The principal antielastase activity in serum and interstitial tissue is α 1 – Antitrypsin. • The principal cellular Elastase activity is derived from Neutrophils (other Elastases are formed by macrophages, mast cells, pancreas, andbacteria)
  19. 19. Protease – Antiprotease mechanism of Emphysema.- Smoking inhibits Antielastase and favours the recruitment of leucocytes and release of Elastase.
  20. 20. 2. Oxidant – Antioxidant Imbalance:Smoking leads to oxidant- antioxident imbalanceNormally lung contains a healthy complement of Antioxidants: - Superoxide dismutase - GlutathioneThese antioxidants protects lung from oxidative damageTobacco smoke contains abundant reactive oxygen species (Free Radicals). ,which deplete antioxidant mechanisms, thereby inciting tissue damageActivated Neutriophils also add to the pool of reactive oxygen speciesAs a result of oxidant injury there is “functional Alpha- 1 –Antitrypsin deficiency”
  21. 21. Pathogenesis of Emphysema: The protease- Antiprotease imbalance and oxidant –antioxidant imbalance are additive in their effects and contributes to tissue damage.Alpha-1 Antitrypsin deficiency can be either congenital or “functional” as aresult of oxidative inactivation.
  22. 22. How smoking produces Emphysema? Cigarette Smoking (i) Nicotine is chemotactic for Neutrophils (ii) Release of Cytokines ( IL -8) (iii) Release of Free radicals from Cigarette smoke (i) Increased Protease (Elastase) activity (ii) Decreased α 1 Antitrypsin activity Emphysema
  23. 23. Morphologic findings of Emphysema Gross Examination:1. In Centri- Acinar type: Lungs are pale , less voluminous with rounded edges. Affects upper 2/3 of the lungs . May demonstrate bullae.2. In Pan – Acinar type: Lungs are pale , more voluminous with rounded edges. Affects lower lung lobes . May obscure heart at autopsy .
  24. 24. Emphysema: Gross Examination:Cut section show dilated air spaces
  25. 25. Bullous Emphysema with large apical andsubpleural bullae
  26. 26. Centrilobular Emphysema: Central areas show marked emphysematousdamage
  27. 27. Bullous Emphysema: This is not a separate category of emphysema.Itrefers to the presence of balloon – like foci of emphysema over 10 mm indiameter. Cases of emphysema with bullae should, where possible, beclassified into one of the four anatomical types. Bullae are prone torupture, causing Spontaneous Pneumothorax
  28. 28. Panacinar Emphysema: involving the entire pulmonary architecture
  29. 29. Microscopic findings in Emphysema • Microscopic examination is necessary to visualize the abnormalfenestrations in the walls of the alveoli, the complete destruction ofseptal walls, and the distribution of damage within the pulmonarylobule.• Histologically there is thinning and destruction of alveolarwalls.• With advanced disease , adjacent alveoli become confluent, creating large airspaces .•With advance disease of the disease , adjacent alveoli fuse,producing even larger abnormal airspaces and possibly blebs orbullae.•Often the respiratory bronchioles and vasculature of the lungs aredeformed and compressed by the emphysematous distortion of theairspaces.
  30. 30. Emphysema : (Microscopic Examination): Loss of alveolar walls.Remaining air spaces are dilated
  31. 31. CLINICAL COURSE OF EMPHYSEMA• The clinical manifestations of Emphysema do not appear until at least onethird of the functioning pulmonary parenchyma is damaged.• Mostly occurs in males and cigarette smokers.• The common clinical features are: - Dyspnoea - Cough - Wheezing - Weight loss• Classically the patient is barrel- chested and dyspneic, withprolonged expiration , and sits forward in a hunched – over position,attempting to squeeze the air out of the lungs with each expiratory effort.•Patient have a pinched face and breathe through pursed lips•Despite of dyspnea the oxygenation is adequate. So these patients aresometimes called ‘pink puffers’• The only reliable and consistently present finding on physicalexamination is slowing of forced expiration.
  32. 32. CHRONIC BORNCHITIS•Definition: Chronic Bronchitis is defined as persistentcough with sputum production for at least 3 months in atleast 2 consecutive years.• It is very common among habitual smokers and inhabitants of smog- laden cities.• When present for years it may lead to: (i) Chronic Obstructive disease (ii) Cor pulomanale and heart failure (iii) Atypical Metaplasia and Dysplasia of the respiratory epithelium.
  33. 33. Types of Chronic Bronchitis1. Simple Chronic Bronchitis: The productive cough raises mucoid sputum but airflow is not obstructed.2. Chronic Mucopurulent Bronchitis: The sputum contains pus because of secondary infection.3. Chronic Asthmatic Bronchitis: Some with chronic bronchitis may demonstrate hyper responsive airways and intermittent episodes of asthma4. Chronic Obstructive Bronchitis: A subpopulation of bronchitis patients develops chronic outflow obstruction
  34. 34. Pathogenesis of Chronic BronchitisTwo sets of factors are important in the genesisof chronic bronchitis:(i) Chronic irritation by inhaled substances likecigarette smoking(ii) Microbiologic infections.
  35. 35. Role of Cigarette Smoking leads in Chronic Bronchitis Cigarette smokingHypersecretionand hypertrophy (i) Direct damage to respiratoryof Bronchial mucous epithelium glands (ii) Decreased ciliary action of airway epitheliumMetplastic formation ofmucin- secreting goblet Increased predispositioncells in the surface epithelium to infectionsof bronchiExcessive mucus productionAir way obstruction
  36. 36. Morphologic Changes in Chronic BronchitisGross Changes: There may be hyperemia, swelling and bogginess ofthe mucous membranes, frequently accompanied by excessivemucinous to mucopurulent secretions layering the epithelialsurfaces. Sometimes heavy casts of secretions and pus fill thebronchi and bronchioles.Microscopic Findings:• The characteristic histologic feature of chronic bronchitis isenlargement of the mucus – secreting glands of the trachea andbronchi .• Number of goblet cells also increase.• Increased Reid index: Reid index is the ratio of the thickness ofthe mucous gland layer to the thickness of the wall between theepithelium and the cartilage.• The bronchial epithelium may exhibit squamous metaplasia anddysplasia. This can , eventually, lead to Carcinoma
  37. 37. •There is marked narrowing of bronchioles caused by goblet cellmetaplasia, mucous plugging, inflammation and fibrosis.
  38. 38. Chronic Bronchitis: the lumen of the bronchus is above. Note the markedthickening of the mucus gland layer ( approximately twice normal) and squamous metaplasia of lung epithelium
  39. 39. Clinical Course of Chronic BronchitisMostly affected men in the 40 -65 years of age group.Productive Cough: In patients with chronic bronchitis , a prominent coughand the production of sputum may persist indefinitely without ventilatorydysfunctionSome patients develop significant COPD with outflow obstruction .This isaccompanied by hypercapnia, hypoxemia and cyanosisDifferentiation of this form of COPD from that caused by emphysema can be made in classic case, but many patients can have both conditionsWith progression, chronic bronchitis is complicated by pulmonaryhyper secretion and cardiac failureRecurrent infections and respiratory failure are common threats
  40. 40. Radiological findings in Chronic Bronchitis
  41. 41. Emphysema Vs Chronic Bronchitis Chronic Emphysema BronchitisAGE ((years) 40 -45 50 -75DYSPNEA Mild; Late Severe; EarlyCOUGH Early; Copious sputum Late; Scanty sputumINFECTIONS Common OccasionalRESPIRATORY Repeated TerminalINSUFFICIENCYCOR PULOMNALE Common Rare ; TerminalAIRWAY RESISTENCE Increased Normal or slightly increasedELASTIC RECOIL Normal LowCHEST RADIOGRAPH Prominent vessels; Large Hyperinflation heartAPPEARANCE BLUE BLOATERS(Due PINK PUFFERS to hypercapnia and hypoxemia ) (Despite of dyspnea the oxygenation is adequate)
  42. 42. ●Patients of emphysema over ventilate and remain welloxygenated and therefore are designated as PinkPuffers.● Patients with chronic bronchitis more often havehypercapnia and severe hypoxemia , so are labeled as Blue Bloaters
  43. 43. •Chronic bronchitis and Emphysemaalmost always co –exist to some degree• Causes of death in patients withCOPD:1. Respiratory acidosis and coma2. Right – sided heart failure3. Massive collapse of lungs secondary to Pneumothorax.
  44. 44. BRONCHIAL ASTHMA Asthma is a chronic relapsingDEFINITION:inflammatory disorder characterized byhyperactive airways, leading to episodic ,reversible bronchoconstriction , due toincreased responsiveness of thetraceobnroncgial tree to various stimuli.
  45. 45. Normal bronchiole/ Asthmatic bronchiole
  46. 46. ETIOLOGY AND CLASSIFICATION OF ASTHMATwo basic types:A) Extrinsic 1. Atopic Or Allergic ( dust , pollen, etc) 2. Occupational (e.g., fumes, cotton, etc) 3. Allergic bronchopulmonary aspergilosos(bronchial colonization with Aspergillus organisms, followed by development of IgG antibodies)B) Intrinsic ( Idiosyncratic) 1. Pharmacologic (e.g., aspirin) 2. Non – Reaginic ( respiratory tract infection)•Both types can be precipitated by cold, stress and exercise
  47. 47. •Atopic Asthma is the most commontype of asthma , its onset is usually inthe first two decades of life, and it iscommonly associated with otherallergic manifestations in the patientas well as in other family members.
  48. 48. ADAM33 GeneA gene expressed by cell typesimplicated in AIR WAYREMODELING seen in Asthma
  49. 49. PATHOGENESIS OF EXTRINSIC ASTHMA “Initiated by Type I Hypersensitivity” Inhalation of allergen (antigen) Simulation of Type 2 helper T cells Production of Cytokines (IL – 2; IL-4; IL -13) Sensitization of mast cells BY IL –2 Production of IgE BY IL -4 Activation of Eosinophils BY IL –5 Stimulation of mucus production BY IL -13 Second exposure Degranulation of mast cells bearing specific IgE molecules Release of vasoactive substances from the mast cell
  50. 50. Pathogenesis of extrinsic asthma – continued Sensitization of CD 4 + T lymphocytes Release of Cytokines (Interleukins; IL) (IL-4;-IL- 5;IL-13) Increased Synthesis of IgE Mast cells degranulation Release of mediators initiating Asthma Leukotrines Prostaglandins Histamine Platelet activating factor Mast cell Tryptase Eosinophilic & Neutrophilic chemo tactic Factor
  51. 51. Pathogenesis of Asthma: Inhalation of allergen (antigen) causes degranulation ofmast cells bearing specific IgE molecules . Release of vasoactive substances fromthe mast cell causes bronchial constriction, oedema, and mucus hypresecretion
  52. 52. PATHOGENESIS OF INTRINSIC ASTHMA Initiated by non- immune mechanisms to various stimuli(1) Respiratory tract infections(2) Cold, Stress, Exercise(3) Aspirin (Decreased Prostaglandins and increased Leukotrines)All can trigger Bronchoconstriction
  53. 53. Extrinsic Asthma Intrinsic AsthmaImmune Mechanisms Non – immune mechanismsFamily History + Family History – NegativeEosinophilia No EosinophiliaSerum IgE –elevated Serum IgE- Normal
  54. 54. MORPHOLOGY OF BRONCHIAL ASTHMA GROSS FEATURES:1. Lungs are over distended with small areas of atelactasis2. There is occlusion of bronchi and bronchioles by thick , tenacious mucus plugs. MICROSCOPIC FEATURES:1. Mucus plugs containing whorls of shed epithelium (Cruschmann’s Spirals) , Eosinophils and Charcot- leyden Crystels (Diamond shaped crystals composed of proteins)2. Air Way Remodeling Characteristic findings of asthma collectively called Air Way Remodeling include: a. Thickening of basement membrane of bronchial epithelium b. Edema and inflammatory infiltrate in bronchial walls with a predominance of Eosinophils and mast cells c. An increase in the size of submucosal glands d. Hypertrophy of the bronchial muscle cells
  55. 55. Comparison of normal bronchiole with that in a patient with asthma .Note the accumulation of mucus in the bronchial lumen resulting from an increase in theNumber of mucus – secreting goblet cells in the mucosa and hypertrophy ofsubmucosal glands .In addition, there is intense chronic inflammation due to recruitment of eosinophils, macrophages and other inflammatory cells. Basement membrane underlying the mucosal epithelium is thickened , and there ishypertrophy and hyperplasia of smooth muscle cells.
  56. 56. CLINICAL FEATURES OF ASTHMA1. Dyspnoea2. Cough3. Wheezing4. Status Asthamticus: It is severe asthmatic paroxysm that does not respond to bronchodilator or corticosteroid therapy and persists for days and even weeks5. Patient may ultimately develop chronic obstructive pulmonary disease COMPLICATIONS OF ASTHMA1. Acute severe bronchial asthma2. Acute respiratory failure3. Pneumothorax4. Side effects of medication e.g. long term corticosteroids, Beta – agonists and Theophyline
  57. 57. BRONCHIACTASIS“Bronchiactasis is the permanentdilation of bronchi and bronchiolescaused by destruction of the muscle andelastic supporting tissue, resulting formor associated with chronic necrotizinginfections”
  58. 58. It is not a primary disease but rathersecondary to persisting infection aobstruction caused by a variety ofcondition . sIt is manifested clinically by cough,fever and expectoration of copiousamount of foul – smelling purulentsputum .To be considered Bronchiactasis thedilation should be permanent
  59. 59. Etiology1. Bronchial obstruction: Common causes of bronchial obstruction which can lead to Bronchiactasis are (i) Tumours (ii) Foreign bodies (iii) Impaction of mucus.2. Congenital or Hereditary Conditions: (i) Cystic Fibrosis: Widespread severe bronchoconstriction caused by secretion of abnormally viscid mucus. (ii) Kartagner Syndrome: Structural abnormalities of cilia impair meucocillary clearance in the airway leading to persistent infections(iii)Immundeficency states: Increased susceptibility to repeated bacterial infections, that can eventually lead to bronchiasctasis .3. Necrotizing or suppurative pneumonias: Particularly due to organisms like Staphylococcus and Klebsialla .
  60. 60. Pathogenesis of BronchiactasisTwo processes are critical and intertwined in the Pathogenecitty ofBronchiactasis: 1. Obstruction 2. Chronic persistent infection Either infection can lead to obstruction or obstruction can lead toinfection . Both then can lead to bronchiactasis . Bacteria involved in Bronchiactasis 1. Staphylococci 2. Streptococci 3. Pneumococci 4. Enteric organisms 5. Anaerobic and microaerophilic organisms 6. Haemophilus Influenzae 7. Pseudomonas Aeruguinosa
  61. 61. Bronchial Obstruction: The obstructing lesion causes a lipid or infectivepneumonia in the distal lung and, if unrelieved distal brochiactasis
  62. 62. MORPHOLOGY OF BRONCHIECTASISGross Examination*Usually lower lobes are involved ; Bilaterally*There is dilatation of bronchi and bronchioles , with inflammatory infiltration especially ofneutrophils. The inflammation and associated fibrosisextend into the adjacent lung tissue. The dilatedBronchi and bronchioles can appear cylindrical, saccular or fusiform..Microscopic Findings: - Acute and chronic inflammatory exudation - Desquamation of lining epithelium - Extensive areas of necrotizing ulceration - Fibrosis Bronchiactasis: Permanent dilatation of bronchi - Necrosis destroys the bronchial or bronchiolar wall and forms a lung abscess.
  63. 63. Bronchiasctasis: Cross section of lung demonstrating dilated bronchiextending to the pleura
  64. 64. CLINICAL FEATURES OF BRONCHIACTESIS1. Severe persistent cough2. Expectoration of foul – smelling , sometimes bloody sputum3. Dyspnea and orthopnea in severe cases4. A systemic febrile reaction may occur when powerful pathogens are present5. The symptoms are usually episodic6. In the full blown cases the cough is usually paroxysmal in nature.7. Such attacks are particularly frequent when the patient rises in the morning and the changes in position lead to drainage into the bronchi of the collected pools of pus.8. Obstructive ventilatory insufficiency can lead to marked dyspnea and cyanosis.9. Patients may have clubbing of fingers
  66. 66. PULMONARY INFECTIONS- Respiratory tract infections are more frequent than infections ofany other organ- The account for the largest number of workdays lost in the generalpopulation.- The vast majority are upper respiratory tract infections caused byviruses.- Bacterial , viral , mycoplasmal and fungal infections of lungs alsoaccount for an enormous amount of morbidity and rank among themajor immediate causes of deaths. The important lung infectionsare: - Pneumonias - Tuberculosis - Lung abscess
  67. 67. PNEUMONIA-Infection of lung parenchyma-It can be classified as:1. On the basis of Aetiological agent involved: (i) Bacterial: Streptococcus Pneumoniae ; Staph Aureus; etc (ii) Viral: Influenza ; Measles (iii) Fungal: Cryptococcus; Candida; Aspergillus. (iv) Others: Pneumocystis carinii; Mycoplasma ;2. On the basis of anatomical pattern: (Most widely usedclassification) (i) Bronchopneumonia (ii) Lobar pneumonia3. On the basis of clinical circumstances: (i) Primary ( in an otherwise healthy person) (ii) Secondary ( With local or systemic defects in defence)
  68. 68. Pneumonias in different clinical settings (“ Pneumonia Syndromes”)1. Community Acquired Acute Pneumonias2. Community Acquired Atypical Pneumonias3. Nosocomial Pneumonias4. Aspiration Pneumonias5. Chronic Pneumonias6. Narcotizing Pneumonias and Lung Abscess7. Pneumonias in immunocompromised
  69. 69. BRONCHOPNEUMONIA- Patchy consolidation of the lung.- Centered on bronchioles or bronchi- Usually in extremes of ages (infancy or old age)-Usually secondary to some pre- existing disease like cancer, cardiac failure, chronic renal failure or cerebrovasclar accidents-Often Bilateral.-Causative organisms may be low – virulence pathogens, especially in an immunocomprised patient, and as such could not cause similar disease in a young , healthy individual.-Typical organisms include - Staphylococci - Streptococci - Haemophilus influenzae - Coliform - Fungi
  70. 70. BRONCHPNEUMONIA: Patchi area of alveoli filled withinflammatory cells
  71. 71. BRONCHOPNEUMONIA: Alveolar exudate mainly Neutrophils seen.Surrounding capillaries are dilated and are filled with red blood cells
  72. 72. LOBAR PNEUMONIA- Affect a large part, or the entire lobe- Relatively uncommon in infancy and old age- Affects males more than females- 90% due to Streptococcus pneumoniae- Affects otherwise healthy individuals- Lobar Pneumonia: Diffuse inflammation affecting the entire lobe.
  73. 73. Strep Pneumococcus
  74. 74. Morphologic Changes in Lobar PneumoniaA classic example of acute inflammation.It involves FOUR STAGES:1st STAGE: STAGE OF CONGESTION: This stage lasts for about 24hours and represents the outpouring of a protein rich exudate intoalveolar spaces, with venous congestion. The lung is heavy,oedematous and red2nd STAGE: STAGE OF RED HEPATIZATION: It last for a few days.In the alveolar spaces there is massive accumulation of neutrophilstogether with macrophages and lymphocytes. Numerous red bloodcells are also extravasated from the capillaries. The lung is red, solidand airless, with a consistency resembling fresh liver.3rd STAGE :GREY HEPATIZATION: It lasts a few days andrepresents further accumulation of fibrin, with destruction of whitecells and red cells. The lung now is gray brown in colour and solid.4th STAGE: RESOLUTION: It occurs at about 8 – 10 days in untreatedcases and represents the resorption of exudate and enzymaticdigestion of inflammatory debris, with preservation of underlyingalveolar wall architecture
  75. 75. Red Hepatization: The congested septal capillaries and extensive neutrophil exudation into alveoli corresponds to early red Hepatization,. Fibrin not yet formedGray Hepatization: Advanced organizingpneumonia featuring transformation of exudatesto Fibrinomyxoid masses richly infiltrated bymacrophages and fibroblasts
  76. 76. CLINICAL COURSE OF PNEUMONIA-The major symptoms of pneumonia are malaise , fever, coughproductive of sputum and chest pain.- The characteristic radiologic appearance of lobar pneumonia is thatof a radiopaque, usually well – circumscribed lobe, whereasbroncho- pneumonia shows focal opacities.
  77. 77. Cough with greenish or yellow phlegmFever with shaking chillsSharp chest painRapid, shallow breathingShortness of breathHeadache
  78. 78. Excessive sweatingClammy skinLoss of appetiteExcessive fatigueConfusion in elderly people
  79. 79. Radiological findings in Pneumonia
  80. 80. Lobar Pneumonia Broncho PneumoniaUsually Unilateral Usually BilateralInvolvement of an entire Patchy involvementlobeUncommon at extreme of More common in infancyages and old age95% cases are due to Organisms of lessStrep Pnemococcus virulence are responsible
  81. 81. Microbiologic association of Pneumonia1.Pneumonia due to Strep Pneumococcus:Respond readily to Penicillin treatment but there areincreasing numbers of Penicillin – resistant strains of PneumococciCommercial Pneumococal vaccines containingcapsular polysaccharides from the common serotypes of Pneumococcus are available, and their proven efficacy mandates their use in patients at risk for the Pneumococal infections
  82. 82. 2. Pneumonia due to Haemophilus InfluenzaeBoth unencapsualated and capsulated forms are importantcauses of community - acquired pneumonias.H. Influenzae is the most common cause of bacterial causeof acute exacerbation of COPD
  83. 83. 2. Pneumonia due to Moraxella Catarrhalis It is increasingly being recognized as a cause of pneumonia especially in elderly.3. Pneumonia due to Staph Aureus: It is an important cause of secondary bacterial pneumonia in children and healthy adults following viral respiratory illness (e.g., measles in children and influenza in both children and adults). It is associated with a high incidence of complications , such as lung abscess and empyema Staphylococcal pneumonia is also an important cause of nosocomial pneumonia
  84. 84. 5. Pneumonia due to Klebsialla PneumoniaIt is the most common cause of gram – negative bacterial pneumonia .It frequently afflicts debilitated and malnourished persons particularly chronic alcoholics.Thick and gelatinous sputum is characteristic because the organism produces an abundant viscid capsular polysaccharide, which the patient may have difficulty in coughing up.
  85. 85. 6. Pneumonia due to Pseudomonas AeruguinosaIt is most commonly seen in nosocomial settingsIt is also common in patients who are neutropenic, usually secondary to chemotherapy ; in patients with extensive burns; and in those requiring mechanical ventilation
  86. 86. 7. Pneumonia due to Legionella Pneumophilia:It is the agent of Legionnaire’s Disease ,an eponym for the epidemic and sporadic forms of pneumonia caused by this organism.It flourishes in artificial aquatic environments such as water – cooling towers and within the tubing system of domestic (portable) supplies.The mode of transmission is thought to be either inhalation of aerosolized organisms or aspiration of contaminated drinking water Can be severe ; In immunocompromised the fatality rate is 30% to 50% PONTIAC FEVER Self limiting upper respiratory tract disease caused byLegionella , without Pneumonic features
  87. 87. Special Types of PneumoniasCommunity – Acquired Atypical PneumoniasNosocomial PneumoniasAspiration Pneumonias
  88. 88. Community Acquired Atypical Pneumonias●Unlike “typical” acute pneumonias , atypical Pneumonia is characterized by: ● Modest amount of sputum ● No Physical findings of consolidation of lung ● White cell counts normal or moderately increased ● May present as a severe upper respiratory tract infection or “chest cold” that goes undiagnosed OR may present as a fulminant life- threatining infection in immunocompromised patients. ● Organisms responsible are: (i) Mycoplasma Pnuemoniae (most common) (ii) Viruses ( most importantly Influenza virus) (iii) Chlamydia Pneumoniae (iv) Rickettsiae
  89. 89. The term “ATYPICAL” denotesthe moderate amounts ofsputum, absence of physicalfindings of consolidation, onlymoderate elevation of whitecells count and lack of alveolarexudates
  90. 90. Morphologic findings in Atypical Pneumonias•The process may be patchy or it may involve whole lobes bilaterally or unilaterally.• Macroscopically the affected areas are red- blue , congested and subcrepitant.• Histologically the inflammatory reaction is largelyconfined within the walls of alveoli. The septa arewidened and edematous ; they usually contain a mononuclearinflammatory infiltrate of lymphocytes , histiocytes andoccasionally plasma cells.• In contrast to bacterial pneumonias the alveolar spaces in atypical pneumonias are remarkably free of cellularexudate.
  91. 91. Viral Pneumonias; The thickened alveolar walls are heavilyinfiltrated with mononuclear leucocytes
  92. 92. Clinical course of atypical pneumonia•The clinical course of atypical pneumonia is extremely varied• May present as a severe upper respiratory tract infection or “chest cold” that goes undiagnosed OR may present as a fulminant life- threatining infection in immunocompromised patients.• Most typically the onset is that of an acute, nonspecifically febrile illness characterized by fever, headache, , malaise, and later cough with minimal sputum.• Chest radiographs usually reveal transient , ill – defined patches , mainly on lower lobes.• Physically findings are characteristically minimal.• Prognosis for a uncomplicated is good; generally complete recovery is the rule.
  93. 93. Typical Pnuemonia Atypical PnuemoniaConsolidation of lung Consolidation is not evidentThe major symptoms of pneumonia are May present as a severe uppermalaise , fever, cough productive of sputum respiratory tract infection or “chest cold”and chest pain. that goes undiagnosed OR may present as a fulminant life – threatining infection in immunocompromised patientsCopious amount of sputum Modest amount of sputumWhite cell count is increased; with a White cell count is usually normalpredominance of NeutrophilsHistology: Inflammatory exudates in alveolar Histology: the inflammatory infiltrate isspaces;Predominant cell is neutrophil largely confined within the walls of alveoli; Predominant cell is Lymphocyte.X-Ray: Findings of consolidation X- Ray: Transient ill – defined patches
  94. 94. Nosocomial Pneumonias OR Hospital Acquired Pneumonias●Defined as the Pneumonias acquired in the course of a hospital stay● Common in patients with: - severe underlying disease, - immunosuppresson, - prolonged antibiotic therapy, - long standing intravascular catheters - patients on mechanical ventilation.● Organisms responsible are: - Enterobactericeae - Pseudomonas - Staph Aureus.
  95. 95. Aspiration Pneumonias●Occurs in markedly debilitated patients or in those whoaspirate gastric contents● The resultant pneumonia is partly chemical , owing to theextremely irritating effects of gastric acid , and partlybacterial● This type of pneumonia is often necrotizing , purses afulminant clinical course, and is a frequent cause of death inpatients predisposed to aspiration ; In those who survive ,abscess is a common complication
  96. 96. PulmonaryTuberculosis
  97. 97. PULMONARY TUBERCULOSISCommunicable chronic Granulomatous diseaseLung is the commonest site for TuberculosisPulmonary Tuberculosis is the leading cause of death globally. It has been estimated that a third of worldpopulation has been infected with tuberculosis.Disease however only occurs in about 10% ofcases of infection, when the balance betweenhost resistance and the pathogenecity of thebacteria tips in favours of the pathogenecity.
  98. 98.  airborne infection  caused by bacillus Mycobacterium tuberculosis spreads person to person or through air most are infected but do not develop the disease  form small black lesions in the lungs
  99. 99. Tuberculosis – Country Pro•Tuberculosis causes a great deal of ill health and an enormous burden on the populations of most low income countries.• According to prevalence and incidence of tuberculosis, Pakistan is on 6th or 7th position in the list of 20 mosteffected countries.• InPakistan there are approximately more than 4 million patients of tuberculosis.• Accordingto a rough estimate, in Pakistan, more than sixty thousands patients die every year due to tuberculosis
  100. 100. • The economic factors, improper diagnostic facilities, nonaffordability of treatment, problem of multidrug resistanceavailability of substandard drugs and poor patientscompliance are heading us towards a state of failure intuberculosis control and treatment.• Thisis regrettable since the disease can be easilydiagnosed and highly effective drugs for its treatmentare available
  101. 101. Mycobacterium – Bacterial characteristicsStrict AerobeSlender RodsAre Acid Fast: Have a high complex lipid in their cell wall that readily bindswith Ziehl – Neelsen ( Carbol Fuchsin) stain BUT subsequently stubbornlyresists decolraization by Acid (Sulfuric Acid)Mycobacterium Hominis is responsible for most casesOther Mycobacterias: - Mycobacterium Bovis - Atypical Mycobacterias , i.e., Mycobacterium Avium Intracellularae. Important in cases of AIDS and immunocompromised .
  102. 102. TUBERCULOSIS PATHOGENESISTypical example of Type –IVHypersensitivityTransformation of Moncytes intoEpithelioid Cells and MultinucleatedGiant Cells under the influence ofTNF and IFN-γ: Antigen presenting cellssecrete IL -12 which in turn acts onCD-4 + T cells to stimulate thesecretion of IL-2, TNF and IFN-γ .IL-2 acts on CD-4 cells (autocrineeffect), while TNF and IFN-γ acts onmacrophages, mobilize them andmodify them into epithelioid cells. Afew epithelioid cells get transformedinto multinucleated giant cells.
  103. 103. Types of Pulmonary Tuberculosis1. Primary tuberculosis2. Secondary Tuberculosis3. Milliary Tuberculosis
  104. 104. Primary TuberculosisThe lungs are usually the initial site of contactbetween tubercle bacilli and humans. The focusof primary infection which is usuallyasymptomatic , is called GHON COMPLEX . Thepulmonary lesion is usually about 10 mm in Primary TB: produces a small mid –diameter and consists of a central zone of zone lesion with involvement of Hilar lymph nodescaseous necrosis surrounded by palisadedepithelioid histiocytes, the occasionalLanghan’s Giant Cells, and lymphocytes.Similar granulomas are seen in lymph nodes that drain affected portion of the lung. In almost all cases, a primary lesion will organize, leaving a fibrocalcific nodule in the lung, and there will be no clinical sequalae. Hence the Ghon complex undergoes fibrosis , often followed by radiologically detectable calcification ( Ranke Complex).However, tubercle bacilli may persist as viable organism for years . In a few cases , complications ,may occur, especially if the individual is immunocomprised.
  105. 105. SECONDARY TUBERCULOSIS-Secondary Tuberculosis represents reactivation of old primary infection. These lesions are nearly always located in the lung apices, sometimes Secondary TB: The lesions are usually apical and often bilaterally, and are about 30 mm in diameter bilateral at clinical presentation. Histologically, typical granulomas are seen, most having central zone of caseous necrosis.Progressino of disease depends on the balance between host sensitivity and organism virulence. Most lesions are converted to fibrocalcific scars.
  106. 106. MILIARY TUBERCULOSISMilliary Tuberculosis may be a consequence ofeither primary tuberculosis or secondarytuberculosis in which there is severe Milliary Tuberculosis: lungsimpairment of host resistance. The disease and many other organs contain numerous smallbecomes widely disseminated, resulting in’ granulomasnumerous small granulomas in manyorgans. Lesions are commonly found in the lungs, meninges,kidneys, bone marrow and liver, but no organ is exempt.The granulomas often contain numerous Mycobacteria , and the Mantoux test is frequently negative.
  107. 107. Natural History and Spectrum of Tuberculosis
  108. 108. GROSS APPEARANCEPrimary pulmonary Tuberculosis: Ghon complex. The gray- white parenchymal focusis under the pleura in the lower part of the upper lobe (topmost arrow) Hilarlymph nodes with caseation are seen( lower most arrows)
  109. 109. Miliary Tuberculosis of the Spleen: The cut surface shows numerousgray – white Granulomas
  110. 110. TUBERCULOSIS: (Gross Specimen)Multiple areas of Caseaous necrosisseen
  111. 111. TUBERCULOSIS LUNG: Multiple well defined granulomas seen. Consisting of aggregation of transformed macrophages – the Epithelioid cells (elongated cells with long pale nuclei andpink cytoplasm. In addition Langhans typeof Giant cells, Lymphocytes and Fibroblastsare also seen.
  112. 112. Acid Fast Bacilli (AFB) stain: Mycobacterium Tuberculosis seen asred rods
  113. 113. AFB - Ziehl-Nielson stain
  114. 114. Microscopic Findings in Tuberculosis:At the active site of involvement, there are both non- caseating and caseating granulomas.The important findings in a case of Tuberculosis are:1. Central caseation2. Epithelioid cells derived from macrophages3. Surrounding collar of lymphocytes .4. Enclosing rim of fibroblasts ( in old lesions)5. Langhan’s type of Giant cells, with multiple nuclei arranged in a horse – shoe pattern.
  115. 115. Caseation Necrosis
  116. 116. Tuberculous Granuloma
  117. 117. LAB DIAGNOSIS OF TUBERCULOSIS1.Blood Complete: -Erythrocytes Sedimentation Rate (ESR) increased - Total Leucocytes Count (TLC) increased in milliary tuberculosis2. Sputum Examination: Early morning sputum for at least three consecutive days is examined. Z.N staning is done and Acid Fast Bacilli (AFB) appear as red rods under microscope3. Chest – X- ray: i. Patchy consolidation in the post apical region ii. Lung cavitation iii. Areas of increased density suggesting caseation iv. Scar tissue produce sharp margins and tends to contract v. Hilar lymphadenopathy vi. Unilateral pleural effusion vii. Milliary spread may be evident
  118. 118. 4. Sputum Culture: Done on L.J medium . After 4 – 6 weeks grey , rough and raised colonies of Mycobacteria appear5. Bectec technique: Radioactive techniques are used to detect Mycobacteria in a given sample in a shorter period as compared to LJ medium6. Fibrooptic Bronchoscopy: With bronchial washing from affected lobe. Useful if no sputum is available7. Biopsies of Pleura, Lymph nodes, Lung and other tissues: It may be required8. Mantoux Test: 0.1 ml of Purified Protein Derivative (PPD) is injected intradermally on the flexor aspect of forearm9. DNA detection by Polymerase Chain Reaction (PCR): By amplification of mycobacterial DNA in clinical samples using PCR .10. Serodiagnosis: By Enzyme Linked Immunosorbent Assay (ELISA), or Immunofluorescence or Column Chromatography
  119. 119. Colony Morphology – LJ Slant
  120. 120. CLINICAL FEATURES OF PULMONARY TUBERCULOSIS1.Fever ( low grade, remittent and appear late each afternoon and then subside)2. Night sweats3. Cough with sputum4. Haemoptysis3. Malaise4. Anorexia5. Cough, first mucoid, later purulent and bloody sputum6. Pleuritic chest painSystemic manifestations are produced by TNF- alpha and IL -1 released from activated macrophages.
  121. 121.  ongoing cough constantly tired loss of weight loss of appetite fever night sweats coughing up blood
  122. 122.  has no symptoms  continuous bad cough does not feel sick  chest pain  coughing up blood or sputum cannot spread TB  weakness or fatigue Usually positive forskin  loss of weight and appetite  chills, fever, night sweats test  positive skin test has normal chest X-ray  may have abnormal chest X- and sputum test ray, or positive sputum smear or culture
  123. 123. Lung Abscess Lung Abscess refers to a localized area ofSuppurative necrosis within the pulmonaryparenchyma , resulting in the formation of one ormore large cavities .
  124. 124. Factors predisposing to Lung Abscess1. Aspiration of infective material : from carious teeth or infected sinuses or tonsils2. Aspiration of gastric contents , usually accompanied by infectious material.3. As a complication of necrotizing bacterial pneumonia4. Bronchial Obstruction particularly with Bronchogenic Carcinoma5. Septic Embolism from septic thrombophelibitis or from infective endocarditis of the right side of heart6. Hematogenous spread of bacteria in disseminated pyogenic infections
  125. 125. Bacteria responsible for Lung AbscessAnaerobic BacteriaPresent in almost all cases of lung abscesses.The most frequently encountered anaerobes are commensals normally found in oral cavity: - Prevotella - Fusobacterium - Bacteriodes - PeptostreptococcusAerobic Bacteria: - Staph Aureus - Beta hemolytic Streptococcus - Nocardia - Gram negative organisms
  126. 126. PNEUMOCONIOSES Lung disease caused by inhaled dusts Dusts may be inorganic ( mineral) of organic Reaction may be inert, fibrous , allergic or neoplastic Co- existing disease may aggravate the reaction When exposed to dust the lung can respond in several ways: (i) Inert -Simple Coal- Worker’s Pneumoconiosis (ii) Fibrous: -Progressive Massive Fibrosis - Asbestosis - Silicosis (iii) Allergic: - Extrinsic Allergic Alveoloitis (iv) Neoplastic: - Mesothelioma - Lung Carcinoma
  127. 127. •For all Pneumoconioses, regulations limiting workerexposure have resulted in a decreased incidence of dust-associated diseases.• Although the Pneumoconioses result from well –definedoccupational exposure to specific agents, there are alsodeleterious effects of particulate air pollution for thegeneral population, especially in urban areas.• Studies have found increased morbidity (e.g., asthmaincidence) and mortality rates in population exposed toincreased ambient air particulate levels, leading to calls forgreater efforts to reduce the levels of particulates inurban air
  128. 128. COAL – WORKER’S PNEUMOCONIOSIS Coal, a form of combustible carbon, has long beenmined for fuel. In Coal Worker’s Pneumoconiosis coal dust isingested by alveolar macrophages , which then aggregate aroundbronchioles .The spectrum of lung findings in coal workers is wide.Different lung lesions due to Coal can be grouped as: 1. Anthracosis: Asymptomatic Anthracosis in which pigmentaccumulates without a perceptible cellular reaction. 2. Simple Coal – Worker’s Pneumoconiosis: In this conditionaccumulation of macrophages occur with little or no pulmonarydysfunction. 3. Complicated or Massive Lung Fibrosis: There is extensive lungfibrosis and lung functions are impaired.
  129. 129. ANTHRACOSISAnthrocosis pigment in the macrophages . Anthracosis is accumulationof carbon pigment from breathing dirty air. Smokers have the mostpronounced anthracosis
  130. 130. Pneumoconiosis; A possible scheme of the pathogenesis of idiopathic pulmonaryfibrosis
  131. 131. Pathogenesis of Pneumoconiosis: Inhaled particulates usually impact at the bifurcation of terminalRespiratory bronchioles , where they are engulfed by alveolar macrophages, which are then stimulatedto secrete (1) various fibrogenic factors that recruit fibroblasts and induce collagen synthesis , (2) toxicfactors that initiate lung injury , and (3) proinflammatory factors that recruit additional inflammatorycellsIGF – Insulin Like Growth Factor; IL- - Interleukins; LTB4 – Leukoterin B4; MIP – Macrophage Inflammatory Factor; PDGF – Platelet Derived Growth Factor; TNF –Tumour Necrosis Factor s
  132. 132. It is known that in a group of minersworking at the same pit for the same length of time ,some will develop massive lung fibrosis and die, whileothers develop little respiratory impairment
  133. 133. Coal – worker’s Pneumoconiosis: Thistransilluminated thin slice of lung showsseveral large black fibrotic nodules
  134. 134. Gross Findings inPnuemoconiocossis
  135. 135. ASBESTOSIS • Asbestos has been used for its fire-m resistant qualitiesfor many centuries. It is used for insulation and themanufacture of brake lining and other friction materials. • Based on epidemiological studies the occupational exposure to asbestos is linked to:(i) Localized fibrous plaques or, rarely diffuse pleural fibrosis(ii) Pleural effusions (iii) Parenchymal interstitial fibrosis ( Asbestosis)(iv) Bronchogenic Carcinoma (v) Mesothelioma (vi) Laryngeal and perhaps other extra pulmonary neoplasms, including colon carcinoma
  136. 136. There are two distinct form of Asbestos: - Serpentine Chrysotiles – flexible and curled structure - Amphiboles – straight stiff formBoth these forms are fibrogenicAsbestos acts as tumour initiator and promoterMorphology: - Diffuse pulmonary fibrosis - Asbestos body: Golden brown, fusiform or beaded rods with atranslucent center. They consist of asbestos fibers coated with an iron –containing proteinaceous material. - Pleural Plaques: these are the most common manifestations ofasbestos exposure ad are well – circumscribed plaques of dense collagen ,often containing calciumMalignant Tumours due to Asbestos exposure: - Bronchogenic Carcinoma - Malignant Mesothelioma
  137. 137. Asbestosis: The fibrous reaction to inhaled asbestos has resulted in a ‘honey – comb’ lung
  138. 138. Asbestosis: Markedly thickened visceral pleura covers the lateral anddiaphragmatic surface of lung .Note also severe interstitial fibrosisdiffusely affecting the lower lobe of lung
  139. 139. Asbestosis Body: Revealing the typical beading and knobbed ends (arrow)
  140. 140. Clinical Course of Asbestosis:The clinical findings are Asbestosis are indistinguishable from any other diffuse interstitial disease.Typically, progressively worsening Dyspnea appears 10 to 20 years after exposureThe disease may remain static or progress to congestive cardiac failure or cor pulmonale and death.The lung or pleural cancer associated with asbestos has a grim prognosis
  141. 141. SILICOSISSilicosis is lung disease caused by inhalation of crystalline silicondioxide (silica).Currently Silicosis is the most prevalent chronicoccupational disease in the world.Silicates are abundant in stone and sand. Consequently, anyindustrial worker involved in the grinding of stone or sand will be atrisk from silicosis.In contrast to pure coal dust, silicates are toxic to macrophages ,leading to their death with release of proteolytic enzymes and theundigested silica particles. The enzymes cause local tissuedestruction and subsequent fibrosis; the silica particles are ingestedby other particles and cycle repeats itself.Nodules tend to form in the lungs after many years of exposure.With progressive fibrosis and increasing numbers of nodules ,respiratory impairment increases.
  142. 142. Several coalescent collagenous silicotic nodules:
  143. 143. SARCOIDOSIS DEFINITION A Granuloma characterized by tubercle- like lesionswithout caseation AETIOLOGY Not settled, but may be an immnunologicalymediated disease caused by an unknown virus PATHOLOGY Site: Multiple lesions affect lungs, skin, lymph nodes, spleen, liver,bones, eyes, salivary glands Microscopic Picture: Small rounded nodules resembling milliarytubercles , formed of epithelioid cells, giant cells and lymphocytes.The giant cells are few in number, larger than those of tuberculosisand contain inclusion bodies, Schaumann bodies and Asteroidbodies. Schaumann bodies are laminated concretions composed ofcalcium and proteins. Asteroid bodies are stellate inclusions.Caseation is absent. Old lesions heal by fibrosis
  144. 144. Course: Spontaneous regression in most cases. Death may resultfrom pulmonary fibrosis, nephroclacinosis or intercurrent infection. Diagnosis: (i) Kvein test : Subcutaneous injection of sterile sarcoid tissuehomogenate is given , it produces granuloma in affected patients. (i) Biopsy: (iii) Serum levels of Angiotensin Converting Enzyme ACE): Raised in 35 – 40% of patients.
  145. 145. Sarcoidosis: Characteristic Sarcoid noncseating Granulomain lung with many Giant cells
  146. 146. TUMOURS OF LUNG- Lung tumours may be primary or secondary. Both arecommon.- In the primary lung tumours following are usuallyincluded (i) Bronchogenic Carcinoma (90 to 95% of tumours) (ii) Bronchial carcinoids ( 5%) (iii) Mesnchymal and other tumours ( 2 to 5%).
  148. 148. BRONCHOGENIC CARCINOMA Most common primary malignant tumour in the world. Directly related to cigarette smoking. It accounts for approximately 95% of primary lung tumours. Associated with occupational exposure tocarcinogens. Overall 5- year survival rate 4 – 7 %. It is a malignant tumour that arises in the lining epithelium of major bronchi usually close to the hilus of the lung
  149. 149. Morphologic Classification of Bronchogenic Carcinoma 1. Squamous Cell Carcinoma 2. Small Cell Carcinoma ( including oat cellcarcinoma) 3. Adenocarcinomas 4. Large Cell Undifferentiated Carcinoma.
  150. 150. Lung Cancers- Bronchogenic carcinomas Develops within the wall or epithelia of the bronchial tree. Epithelial cells that develop abnormal chromosomal changes (dyplastic cells) turn into cancer and invade deeper tissue.
  151. 151. AETIOLOGY & PATHOGENESIS OF BRONCHOGENIC CARCINOMA 1.TOBACCO SMOKING- Squamous cell and small cell lung carcinoma are morecommon in males because of increased cigarette smoking- There is 20 times increased risk of lung cancer with 40cigarettes per day for several years- About 80% of lung cancers occur in active smokers- Cigarette smoke contains: i. Initiators for carcinogenesis: Polycyclic aromatichydrocarbons like Benzopyrene ii. Promoters for carcinogenesis: Phenol derivatives iii. Radio – active elements: C – 14 , K - 40
  152. 152. In lung cancer it has been estimatedthat 10 to 20 mutations have occurred bythe time the tumour is clinically apparent. The dominant oncogenes in Bronchogeniccarcinoma: - c- myc - K –ras - Mutation in tumuor suppressor gene- p -53
  153. 153. Risk of Lung Cancer in Smokers
  154. 154. Risk of Lung Cancer in Smokers 70 Relative Risk for CA of lung 60 50 40 30 20 10 0 Non Smoker 1 to 10 11 to 20 21 to 30 31 to 40 > 41 No. of Cigarettes/day
  155. 155. Tobacco SmokeSquamous Metaplasia of Respiratory Epithelium Dysplasia Carcinoma in situ Lung Cancer
  156. 156. Adverse effects of smoking:The more common on the left and the somewhat less common on the right
  157. 157. Association between Cigarette smoking and Carcinoma Bronchogenic Carcinoma Carcinoma Lip Carcinoma Tongue Carcinoma Floor of Mouth Carcinoma Pharynx Carcinoma Larynx Carcinoma Esophagus Carcinoma Urinary bladder Carcinoma Pancreas Carcinoma Kidney
  158. 158. 2. Industrial Hazards i. Radiations ii. Minors of radioactive ores iii. Asbestosiv. Arsenic v. Chromiumvi. Uraniumvii. Nickelviii. Vinyl chloride ix. Mustard gas 3. Air Pollution It also contributes to lung cancer
  159. 159. . Molecular Genetics- Ultimately different type of exposures thought to act by causinggenetic alterations in lung cells, which accumulate and ultimatelylead to neoplasia- In lung cancers it is estimated that 10 to 20 genetic mutations haveoccurred by the time the tumour is clinically apparent- There is activation of Oncogenes and inactivation of TumourSuppressor Genes.- The dominant Oncogenes involved are: - c- myc - K- ras- The commonly inactivated or deleted gene is p-53
  160. 160. MORPHOLOGY OF BRONCHOGENIC CARCINOMA 1. SQUAMOUS CELL CARCINOMAThis is the type of lung cancer most commonly associated withcigarette smoking. The tumours are almost always hilar and arethought to arise from squamous metaplasia. Microscopically range from well – differentiated squamous celltumours showing keratin pearls and inter- cellular bridges to poorlydifferentiated tumours having only minimal residual squamous cellfeatures
  161. 161. Squamous Cell Carcinoma (30%) Obstructive manifestations (nonspecific) Nonproductive cough or hemoptysis Pneumonia Atelectasis Pain is a late symptom Surgical intervention (in the absence of mets)
  162. 162. SQUAMOUS CELL CARCINOMA LUNG: (Gross Examination) Arising centrally in the lung .In almost all patterns the neoplastic tissue is gray- white in colour andfirm to hard in consistency
  163. 163. Squamous cell carcinoma usually begin as central (hilar) masses andgrow contagiously into the peripheral parenchyma .
  164. 164. Well differentiated squamous cell carcinomashowing keratinization
  165. 165. SQUAMOUS CELL CARCINOMA: (Microscopic Examination) At theupper left a cell nest or keratin pearl is seen. At the right tumouris less well differentiated and several mitotic figures are seen.
  166. 166. SQUAMOUS CELL CARCINOMA LUNG: (Microscopic Examination)Pink cytoplasm with distinct cell borders and intracellular bridgescharacteristic for squamous cell carcinoma seen. Such features areseen in well differentiated tumour (those that more closely mimicthe cell of origin.
  167. 167. Squamous Cell Carcinoma Lung
  168. 168. Squamous Cell Carcinoma – Evolution AThe precursor lesions of squamous cell carcinoma may antedate the appearance ofinvasive tumour by years. Some of the earliest (and “mild”) changesin smoking - damaged respiratory epithelium include goblet – cell hyperplasia
  169. 169. Squamous Cell Carcinoma – EvolutionB Basal Cell or (reserve cell) hyperplasia
  170. 170. Squamous Cell Carcinoma – EvolutionC Squamous Metaplasia
  171. 171. Squamous Cell Carcinoma – EvolutionMore ominous changes include theappearance of squamous dysplasia characterized by :-The presence of disordered squamous epithelium, - Loss of nuclear polarity,- Nuclear hyperchromasia,- Pleomorphism, and- Mitotic figures D
  172. 172. Squamous Cell Carcinoma – Evolution ECarcinoma – in situ (CIS): It is the stage that immediately precedes invasivesquamous cell carcinoma , and apart from the lack of basement membranedisruption is CIS , the cytological features are similar to those frank carcinoma
  173. 173. Squamous Cell Carcinoma – Evolution FUnless treated the CIS will eventually progress to invasive cancer
  174. 174. 2. SMALL CELL CARCINOMA Also known as ‘OAT CELL CARCINOMA’because the small nuclei are thought to resemble oatgrains. Usually arise in a hilar bronchus. Microscopically highly cellular tumour composedof small cells with hyperchromatic nuclei and indistinctnucleoli. The tumour cells are fragile and often showfragmentation and “Crush Artifacts” in small biopsyspecimens Close apposition of tumour cells that have scantcytoplasm show “Nuclear Molding”
  175. 175. Small Cell (Oat cell) Carcinoma (20-25%) Ectopic Hormone Production Paraneoplastic Syndromes Worst prognosis Chemotherapy & Radiation Temporary remission
  176. 176. SMALL CELL (OAT CELL) CARCINOMACut surface of the tumour has a soft,lobulated, white or tan appearance.The tumour has caused theobstruction of main bronchus
  177. 177. SMALL CELL CARCINOMA: (Microscopic Examination) Small darkblue cells with minimal cytoplasm are packed together in sheets
  178. 178. Small cell carcinoma lung with islands of smalldeeply basophilic cells and areas of necrosis
  179. 179. 3. ADENOCARCINOMAS- These are usually peripheral- Microscopic features are: i. Neoplastic cells are cuboidal to columnar ii. Secrete mucin in 80% of cases iii. Form following structures: - Papillary - Solid and Scirrhous - Acinar iv. Considered as the most common lung cancer in women and non- smokers.
  180. 180. Adenocarcinoma (35-40%)Asymptomatic Routine chest x-ray Pleuritic chest pain Shortness of breath Unpredictable mets, usually early Pulmonary arterial system Mediastinal lymph nodes Surgical intervention (in the absence of mets)
  181. 181. •The incidence of Adenocarcinoma is increasing and somestudies show it as the most common lung carcinoma inwomen.• The basis for this change is unclear. A possible factor isthe increase in women smoking, but this only highlights ourlack of knowledge about why women tend to developAdenocarcinoma.• One interesting postulate is that changes in cigarette type ( filter tips, low tar and low nicotine) have caused smokers toinhale more deeply and thereby expose more peripheralairways and cells ( with a predilection to Adenocarcinoma) tocarcinogens.
  182. 182. ADENOCARCINOMA OF LUNG:Adenocarcinomas and anaplasticlarge cell carcinoma tend to occurmore peripherally.
  183. 183. Adenocarcinoma lung showing gland formation
  184. 184. Adenocarcinoma Lung
  185. 185. Adenocarcinoma Lung – Evolution AThe evolution of adenocarcinoma of the lung is thought to occur through asequence that begins with a small well – demarcated lesion known as Atypical Adenomatous Hyperplasia , or AAH ( arrowheads)
  186. 186. Adenocarcinoma Lung – Evolution BAtypical Adenomatous Hyperplasia progresses toBronchoalveolar Carcinoma orBAC (an insitu phase that grows along existing structures and does not demonstratestromal invasion)
  187. 187. Adenocarcinoma Lung – Evolution CIn situ carcinoma ultimately culminates into Invasive Adenocarcinoma , withstromal invasion and parenchymal destruction
  188. 188. 4. LARGE CELL CARCINOMA- Peripherally forming bulky masses-Microscopic features: i. Composed of Anaplastic cells with large vesicularnuclei ii. Cells may be: - Multinucleated giant cells - Clear cells - Spindle cells
  189. 189. Large Cell Carcinoma (10-15%) Undifferentiated, process of exclusion High incidence of mets Surgical intervention is palliative Obstructive pneumonitis Pleural effusions Non responsive to radiation or chemo
  190. 190. Large cell carcinoma lung showing pleomorphic, anaplastic tumourcells and absence of squamous or glandular differentiation
  191. 191. SPREAD OF BRONCHOGENIC CARCINOMA1. DIRECT: i. Into lung. ii. Into pleura, pleural cavity and intrathrocic structures2. LYMPHATIC To scalene, clavicular, supraclavicular lymph nodes3. HAEMATOLOGICAL: To: i. Bone ii. Brain iii. Liver iv. Adrenals
  192. 192. NSCLC staging (TNM grouping)
  193. 193. NSCLC staging (TNM grouping)
  194. 194. NSCLC – metastases (M1) M0 – No metastasis M1 – Metastasis present
  195. 195. TNM STAGING OF BRONCHOGENIC CARCINOMAOCCULT: - TX N0 M0 - No clinical or radiographic evidence of primary tumour or of spread , but bronchopulmoanry secretions contains malignantcellsSTAGE I: - T1 N0 MO / T1 N1 MO - Tumour of 3 cm or lessStage II: - T2 N1 M0 - Tumour greater than 3 cm in diameter invading the pleura withinvolvement of ipsilateral hilar nodes but without distant metastasis.Stage III: - T3 N2 M1 - Any tumour that: - invades pleura and adjacent structures(T3) - involves contralateral Mediastinal nodes(N2) - show distant metastasis (M1)
  196. 196. CLINICAL FEATURES OF BRONCHOGENEIC CARCINOMA1.Chronic cough2. Expectoration3. Dyspnea4. Wheezing5. Weight loss6. Age incidence: 40 - 70 years ; Male to female ratio = 2:1; More in cigarette smokers
  197. 197. PARANEOLASTIC SYNDROMES SEEN IN BRONCHOGENIC CARCINOMA “Paraneoplastic syndromes are symptom complexes which cannot be readily explained by local or distant spread of the tumouror by the elaboration of hormones indigenous to the tissue oforigin” Bronchogenic Carcinoma is one of the tumours in whichParaneoplastic syndromes are mostly seen.
  198. 198. Common Paraneoplastic Syndromes seen in Bronchogenic Carcinoma3 to 10% patients of Bronchogenic Carcinoma develop clinically overt Paraneoplastic syndromes. These include:(1) Hypercalcemia: caused by parathyroid hormone – related peptide(2) Cushing Syndrome: From increased production of Adrenocorticotropic hormone(3) Syndrome of Inappropriate Production of Antidiuretic Hormone (SIADH):(4) Neuromuscular Syndromes: including Myasthenia syndrome, peripheral neuropathy and polymyositis(5) Clubbing of fingers and hypertrophic pulmonary osteoarthropathy(6) Haematologic manifestations: including migratory thrombophelibitis and disseminated intravascular coagulation
  199. 199. Adult Respiratory Distress Syndrome(ARDS) (Diffuse Alveolar Damage)Descriptive terms for a syndrome caused by diffuse alveolarcapillary damage.ARDS has many synonyms (including adult respiratory failure, shock lung, diffuse alveolar damage, acute alveolar injury and wet lungs) areIt is characterized clinically by the rapid onset of severe life threatining respiratory insufficiency , cyanosis, and severe arterial hypoxemia that is refractory to oxygen therapy and that may progress to extra pulmonary multisystem organ failure.ARDS is a well – recognized complication of numerous anddiverse conditions ,including both direct injuries to the lungand systemic disorders
  200. 200. Conditions associated with development of ARDSInfections: Sepsis*; Diffuse pulmonary infections*;Gastric aspiration*Physical injury: Mechanical trauma including headinjuries* ; Pulmonary contusions; Near drawing;Fractures with fat embolism; Burns; IonizingradiationsInhaled Irritants: Oxygen toxicity; Smoke; Irritantgases and chemicalsChemical Injury: Heroin or methadone overdose; etcHaematologic Conditions: Multiple transfusions;Disseminated Intravascular Coagulation (DIC).PancreatitisUremiaCardiopulmoanry Bypass*More than 50% of cases are associated with these four conditions
  201. 201. Morphological changes in ARDS- Lungs are heavy, edematous and boggy.- Lungs exhibit congestion, interstitial and intra-alveolaredema and inflammation.- Fibrin deposition- Alveolar walls become lined with waxy hyalinemembranes .These hyaline membranes are consist of fibrin-rich edema fluid mixed with cytopaslmic and lipid remnantsof necrotic epithelial cells.- Fatal cases often have superimposed bronchopneumonia
  202. 202. Diffuse alveolar damage in ARDS: Some of the alveoli are collapsed , othersdistended. Many contain diffuse proteinaceous debris, desquamated cells,and hyaline membranes.
  203. 203. Adult Respiratory Respiratory DistressDistress Syndrome Syndrome inin Adults NeonatesCaused by diffuse damage Due to deficiency into alveoli pulmonary surfactant
  204. 204. Pathogenesis of ARDS-The capillary defect in ARDS is believed to beproduced by an interaction of leukocytes andmediators , including cytokines, oxygen radicals,complement and eicosanoids that damage theendothelium and allows fluid and protein to leakacross it.
  205. 205. Clinical Course of ARDS-Patients who develop ARDS are usually hospitalized for one of thepredisposing condition and initially they have no pulmonarysymptoms.- X-ray: Diffuse bilateral infiltrates- It is characterized clinically by the rapid onset of severe lifethreatining respiratory insufficiency , cyanosis , and severe arterialhypoxemia that is refractory to oxygen therapy- Therapy of ARDS is difficult and this disorder is frequently fatal
  206. 206. PULMONARY THROMBOEMBOLISMCause and Incidence: The most serious form of thrombembolism ispulmonary embolism, which may cause sudden death. It has anincidence of 20 to 25 per 100,000 hospitalized patientsOver 90% of Pulmonary Emboli originate in the deep veinsof the leg (phelebothrombosis). More rarely, thrombi in pelvicvenous plexus are the source.Pulmonary embolism is common in the following conditions thatpredispose to the development of phlebothrombosis: (i) Immediate post operative period (ii) Immediate post partum period (iii) Lengthy immobilization in bed (iv)Cardiac Failure (v) use of Oral Contraceptives
  207. 207. CLINICAL EFFECTS OF PULMONARY EMBOLISM The size of the embolus is the factor most influencing the clinical effects of pulmonary embolism1. Massive Emboli: Large emboli (several centimeter long) may lodge in the outflow tract of the right ventricle or in the main pulmonary artery, where they cause circulatory obstruction and Sudden Death .2. Medium Sized Emboli: obstruction of medium sized arteries may cause Pulmonary Infarct3. Small Emboli: Small emboli lodge in minor branches of pulmonary artery with no immediate effects. In many instances, the emboli either fragment soon after lodgment of dissolve during fibrinolysis, in which case clinical effects are minimal. If numerous small emboli occur over a long period, however, the pulmonary microcirculation may be so severely compromised that Pulmonary Hypertension
  208. 208. Pathogenesis of Pulmonary Thromboembolism: The thrombus usually originates from thedeep leg veins and after detachment becomes lodged in the pulmonary artery vasculature,causing sudden death (if massive), pulmonary infarction ( if small), or Pulmonaryhypertension (if small and multiple)
  209. 209. Saddle pulmonaryembolus
  210. 210. PULMONARY HYPERTENSION AND VASCULAR SCLEROSIS• The pulmonary circulation is normally one of low resistance , andpulmonary blood pressure is only about one eighth of systemic bloodpressure.• Pulmonary hypertension takes place when mean pulmonarypressure reaches one fourth of systemic level.• Normal pulmonary arterial pressure averages 25/10 (mean 15 mmHg). If pressure exceeds 30/15 (mean 20 mm Hg) it is called pulmonaryhypertension.• Pulmonary Hypertension takes place secondary to structuralcardiopulmonary conditions that increase : - Pulmonary blood flow - Pulmonary pressure - Pulmonary blood flow and pressure, both. - Increased Pulmonary vascular resistance - Left heart resistance to blood flow.
  211. 211. Causes of Pulmonary Hypertension1. Chronic Obstructive or Interstitial Lung Disease: Patients with emphysema have hypoxia as well as destruction of lung parenchyma and hence have fewer alveolar capillaries . This causes increased pulmonary arterial resistance and secondarily , increased pressure.2. Antecedent Congenital or Acquired Heart Disease: Pulmonary hypertension occurs in patients with mitral stenosis . In mitral stenosis an increase in left atrial pressure leads to an increase in pulmonary venous pressure and, consequently , to an increase in pulmonary artery pressure3. Recurrent Thromboemboli: Patients with recurrent pulmonary emboli may have pulmonary hypertension owing to a reduction in the functional cross sectional area of the pulmonary vascular bed brought about by the obstructing emboli which in turn , leads to an increase in pulmonary vascular resistance
  212. 212. Symptoms of Pulmonary Hypertension• Symptoms of underlying disease and rightheart failure are usually prominent .• Symptoms directly related to pulmonaryhypertension are: -exertional syncope - chest pain - recurrent hemoptysis.
  213. 213. Diseases of Pleura•The pleura is composed of connective tissue lined with mesothelial cellsforming two opposing surfaces, the visceral pleura covers the lungs and theparietal pleura covers the thoracic cage.1. Accumulation of Fluid in pleural cavity• Proteinaceous fluid, blood, lymph or air may form collections.2. Inflammation• Inflammation is common, causing sharp localized chest pain ( pleurisy)• Pleurisy seen with pneumonia, pulmonary tuberculosis, pulmonaryinfarction, connective tissue diseases, etc.3. Tumours• Secondary tumours usually from lung or breast carcinomas . • Mesothelioma
  214. 214. Disorders due to collection of fluid and air in the pleural cavitiesDisorder Collection CausesHaemothorax Blood Chest injury, ruptured aortic aneurysmHydrothorax Low protein fluid Liver failure, cardiac (transudate) ; High failure, renal failure, protein fluid (Exudate) tumours, infection, inflammationChylothorax Lymph Neoplastic obstruction of thoracic lymphaticsPneumothorax Air •Spontaneous following rupture of alveolus or bulla in emphysema or tuberculosis • Traumatic, eg, following penetrating injuries of the chestPyothorax Pus Infection
  215. 215. Causes of Pleural EffusionExudate:( Protein more than 3 gram/dl)1. Tuberculosis2. Malignancy3. Para pneumonic4. Pulmonary infarction5. Connective tissue disorders (SLE, Rheumatoid Arthritis) Transudate: (Protein less than 3 grams/dl)1. Congestive Cardiac Failure2. Hypoproteinemia including Nephrotic Syndrome3. Meig’s syndrome ( it can be exudate to)
  216. 216. Exudate VS Transudate Transudate ExudateAppearance Clear Usually cloudy or turbidColour Watery Turbid to purulent or bloodySpecific Gravity Less than 1.016 1.016 or moreCell Count Less than 1 X 10 9/l More than 1 X109/lDLC Lymphocytes and Neutriophils early but mesothelial cells lymphocytes laterRBC Absent Often presentClot formation None UsualGlucose Same as serum Usually same as serum or reduced.
  217. 217. Transudate ExudateTotal Protein Less than 3 gram/dl 3.0 g/dl or morepH More than 7.5 Less than 7.5Rivolta Test Negative or faint PositiveLDH Normal IncreasedPathogenesis Gradient of serum and Usually involves pleural fluid inflammation which maintained because of increases the intact vascular permeability of endothelium pulmonary and pleural vasculature permitting the passage of fluid with high protein content
  218. 218. Tumours of PleuraSecondary Tumours of Pleura-From Lungs-From Breast- From Ovaries- Malignancies from any organ can metastasize to pleuraPrimary Tumours of Pleura- Benign Mesothelioma-Malignant Mesothelioma
  219. 219. Benign Mesothelioma•A localized growth that is often attached to the pleural surfaceby a pedicle.• Tumour may be a small or may reach enormous size.• Usually do not produce pleural effusion• Grossly consist of dense fibrous tissue with occasional cysts filledwith viscid fluid• Microscopically the tumour show whorls of reticulin andcollagen fibers along with interspersed spindle cells resemblingfibroblasts.• Benign Mesothelioma has no relationship with Asbestos
  220. 220. Malignant Mesothelioma• Uncommon , but have assumed great importance because oftheir association with Asbestos.• In coastal areas with shipping industries and in South Africanmine areas upto 90% of malignant Mesothelioma are associatedwith Asbestos.• A diffuse lesion that spreads widely in the pleural space.Associated with extensive pleural effusion.• The effected lung is ensheathed by a thick layer of soft gelatinousgrayish pink tumour tissue.
  221. 221. • Microscopically the malignant Mesothelioma has twoappearances: 1. Sarcomatoid Type: Mesothelial cells tend to develop as amesenchymal mass. Microscopically appear as a spindle cell sarcoma 2. Epithelial Type: Microscopically cells appear like epithelium liningcells. It consists of cuboidal, columnar or flattened cells forminga tubular or papillary structure, resembling Adenocarcinoma
  222. 222. Pleural Mesothelioma: The tumour envelopsthe lung
  223. 223. Malignant Mesothelioma, epithelial type: The tumor cells are immunoperoxidasepositive for keratin, as shown (brown), but would be carcinoembryonic antigennegative