RESPIRATORY PATHOLOGY [Autosaved].ppt

Respirator y Pathology  Anatomy Nasal cavity; nares, nasal septum, vestibule, choana, turbinates, cribriform plate Mucosal lining: stratified squamous epithelium, pseudostratified ciliated columnar epithelium Paranasal sinuses: ethmoid, frontal, sphenoid, maxillary;...

Respirator y Pathology  Anatomy Nasal cavity; nares, nasal septum, vestibule, choana, turbinates, cribriform plate Mucosal lining: stratified squamous epithelium, pseudostratified ciliated columnar epithelium Paranasal sinuses: ethmoid, frontal, sphenoid, maxillary; respiratory epithelium Nasopharynx: above and behind the soft palate; ostium of eustachian tube; lined by squamous and respiratory epithelium  Common nasal lesions Infectious rhinitis: Aka common cold. Viral infection; replication; necrosis and shedding of degenerate epithelial cells; mucosal oedema; rhinorrhoea; secondary bacterial infection Allergic rhinitis: Aka hay fever; type I hypersensitivity reaction; due grass, pollens; mixed seromucinous exudate and submucosal oedema nasal blockage Nasal polypoid lesions: nasal obstruction – Allergic polyps: recurrent allergic reactions; multiple and bilateral; many E; oedema – Inflammatory polyps: like above – Papillomas: inverted papilloma, squamous papilloma Nose bleed (epistaxis): traumatic; Little’s area Allergic polyp: the core consists of oedematous tissue; note the normal surface respiratory epithelium Inverted papilloma: broad epithelial island push into the stroma; this is not a true invasion  Common URT lesions Sinusitis: Obstruction of the ostia; acute or chronic (tobacco, industrial, polyps); complications include: mucocoele (±empyema), osteomyelitis (±orbital cellulitis, orbital abscess), septic thrombophlebitis, meningitis; epidural abscess Acute tonsillitis: Strep. pyogenes (gp A ß-haemolytic) Adenoids: Follicular hyperplasia of pharyngeal lymphoid tissue; Waldeyer's ring (nasopharyngeal tonsils + palatine tonsils) Peri-tonsillar abscess (quincy): results from poorly treated acute bacterial tonsillitis; parapharyngeal abscess and weakening wall of carotid artery; travel along carotid sheath to mediastinum or base of skull  Common tumours of the nose,sinuses & nasopharnx Nasopharngeal Angiofbroma Schneiderian Papilloma ( inverted papilloma already mentioned) Olfactory Neuroblastoma Nasopharyngeal carcinoma; has an association with EBV infection. Normal Lung function 1 The normal intake of air is app 7L/min;about 5L/min are available for alveolar ventilation A definite flow of air is maintained as far as the terminal bronchioles (TB). Beyond this point [i.e. from respiratory bronchiole (RB) downwards] the actual flow of air ceases( because; diameter of RB=diameter of TB) and gas exchange occurs by diffusion At the level of alveolar ducts(AD) the disparity in air pressure falls to zero and movement of respiratory gases is by diffusion  Normal lung function 2 Three factors are involved in the maintenance of adequate respiration: 1) adequate intake of air or adequate air supply to alveoli 2) rapid diffusion of gases along alveolar ducts and through alveolar walls 3) adequate perfusion of pulmonary circulation Interference with any of these factors will result in respiratory embarrassment(dyspnoea),hypoxaemia and even respiratory failure  Inadequate air supply to the alveoli (hypoventilation) May due to lesions and diseases which interfere with the mechanics of respiration e.g. 1) CNS lesions affecting the respiratory center 2) paralysis of muscles of respiration as in poliomyelitis 3) injuries and deformities of the thoracic skeleton e.g. fracture of ribs and kyphosis 4) pleural disease preventing lung expansion as in pleural effusion or pneumothorax N/B the commonest cause of hypoventilation is bronchial obstruction which may be reversible due to bronchial spasm as in asthma or irreversible in chronic obstructive pulmonary disease  Impaired diffusion of gases Three machanisms may interfere with diffusion: 1) Reduction in the total alveolar surface available for diffusion, e.g. consolidated airless lobe in pneumonia, fibrosis of lung, tumour growth, advanced TB 2) Increase in distance over which diffusion takes place as in emphysema 3) increase in the thickness of the alveolar capillary menbrane. The last point is of very little practical importance  Altered pulmonary perfusion Interference with the pulmonary circulation may occur in four main ways: 1) Occlusion of larger vessels by multiple emboli 2) Slowing of the pulmonary circulation as in venous congestion due to left heart lesions or congenital left- right shunts 3) Reduction in the pulmonary capillary bed by diffuse lung disease such as fibrosis, emphysema or extensive tuberculosis 4) Pulmonary vascular spasm due to hypoxia. Permanent changes may occur in vessels if the hypoxia is unrelieved  Altered pulmonary perfusion cont N/B : in addition to hypoxaemia, inadequate perfusion tends to cause retention of C02 In chronic lung disease,ventilation,diffusion and perfusion disorders are present in varying degrees Even in the normal lung there is imbalance between ventilation and perfusion: the upper area of lung is better ventilated than perfused while the base is better perfused In many lung diseases this imbalance is increased. Admixture of well and poorly oxygenated blood results in hypoxaemia  Atelectasis – 1 Collapse of expanded lung tissue. This is divided into 4 types: Obstructive atelectasis: complete obstruction of an airway, which in time leads to absorption of the oxygen trapped in the dependent alveoli without impairment of blood flow through the affected alveolar walls; excessive secretions or exudates within smaller bronchi: – COPDs: bronchial asthma, chronic bronchitis, bronchiectasis – postoperative states: airway irritation, abdominal tenderness – aspiration of foreign bodies: lentil seed, gastric aspiration content (vomitus), blood – tumours  Atelectasis – 2 Compressive atelectasis: pleural cavity is partially or completely filled by fluid exudates, tumour, blood, or air Patchy atelectasis: loss of pulmonary surfactants (neonatal respiratory distress syndrome) and in adult DAD Contraction atelectasis: panlobar retraction of the lung mostly due to pulmonary fibrosis  Atelectasis: Locate the lung in the picture. The right hemithorax was filled with blood (haemothorax). This is a fatal complication of road traffic accident and penetrating injuries (stab on chest). Obstructive asphyxia by gastric contents. This occurred just before death and hence did not give time for atelectasis For completeness the stomach has been opened to reveal this material which is identical to that seen in tracheal lumen. Clotted blood within the tracheal lumen: another peri-mortem obstructive asphyxia  Pulmonary oedema Presence of fluid in the alveolar spaces Produced by 2 basic mechanisms: – Haemodynamic alterations – Increased vascular permeability (microvascular injury) of alveolar capillary endothelium When it is massive, it quickly results in death from respiratory failure Grossly, the lung is heavy The cut surface is water logged and oozes water which is usually frothy (rain-soaked clothes dripping with water) Flotation test is usually positive if it is massive  Pulmonary oedema (2) Haemodynamic oedema Increased hydrostatic pressure – left sided heart failure (systemic hypertension, mitral stenosis) – volume overload (overdose of intravenous infusion) – pulmonary vein obstruction Decreased oncotic pressure – hypoalbuminaemia (nephrotic syndrome, chronic liver disease, protein-losing enteropathy) Lymphatic obstruction (rare) – tumour – hilar lymphadenopathy  Pulmonary oedema (3) Oedema due to microvascular injury Infectious agents: virus, Mycoplasma Inhaled gases: oxygen, sulphur dioxide, smoke Liquid aspiration: gastric contents, near-drowning Drugs and chemicals – chemotherapeutic agents: bleomycin – other medications: amphotericin B, colchicine, gold – others: heroin and other narcotics, kerosene Shock, trauma, and sepsis Miscellaneous: acute pancreatitis; massive fat, air, or amniotic fluid embolism; uraemia; heat; diabetic ketoacidosis; DIC, radiation Pulmonary oedema: Excess frothy fluid exuding from the cut surface of the lung (= rain-soaked clothes) Pulmonary oedema Normal lung parenchyma: note that the alveolar spaces contain air. Compare with emphysema. Pulmonary oedema: the alveolar spaces are filled with eosinophilic fluid. The lung is airless. Note also the vascular congestion Pulmonary oedema with pulmonary congestion; the latter suggests that the oedema is of haemodynamic origin  Pulmonary hypertension Increased arterial blood pressure of the pulmonary vasculature It could be primary (idiopathic) or secondary. Secondary pulmonary hypertension results from existing cardiac(congenital or acquired with left sided heart failure) or pulmonary disease (chronic obstructive or interstitial lung dx), etc It principally involves the muscular arteries It has 2 deleterious effects: – Thickening of intima and wall of the small vessels and atherosclerosis of the large vessels; both of which reduce pulmonary blood flow and result in respiratory insufficiency – Right heart failure (cor pulmonale) Mild to moderate pulmonary hypertension: Observe the mild thickening of the wall of the arteries Severe pulmonary hypertension: Note thickening of the wall of a small artery (“onion-skin” hyperplasia) Severe pulmonary hypertension: Note the stenotic lumen (arrow)  Causes of 2o pulm. hypertension Increased pulmonary blood flow – Cardiac left-to-right shunts: ASD, VSD, PDA Pulmonary venous congestion: pressure in left atrium and ventricle congestion of pulmonary veins and capillaries reflex pulmonary arterial and arteriolar pressure in order to protect the vascular bed – Mitral and aortic stenosis – Post-myocardial infarction involving left side (with failure) – Systemic hypertension (with failure) Destruction of lung capillary bed – COPDs, interstitial fibrosis Mechanical arterial occlusion – Multiple pulmonary thromboemboli, foreign body emboli in drug addicts  Pulmonary infarction Ischaemic necrosis resulting from the occlusion of a branch of the pulmonary artery Grossly this is a red infarct due to bleeding into the infarcted area from bronchial vessels It can be caused by occlusion of the pulmonary artery by atherosclerotic thrombi or thromboemboli; because of the collateral perfusion by the bronchial tree, another cardiac or pulmonary lesion is often required before a pulmonary infarct is formed It heals with fibrosis resulting a retracted zone at the periphery of the lung – contraction atelectasis A large lesion can result in sudden death; smaller lesion will produce chest pain, dyspnoea, fever, cough Pulmonary infarction: Note the large red infarct at the periphery (right) Pulmonary infarction Pulmonary infarction Pulmonary infarction: Coagulative necrosis showing ‘ghosty’ outline of the alveoli with secondary haemorrhage  Pulmonary thromboembolism Originates from deep vein thrombosis of the calf and pelvic veins in 95% of cases Precipitating factors and other causes include: – Stasis of blood flow: chronically ill patients, bed-ridden patients, following a major surgery, cardiac failure, air-travel – Hypercoagulable states: thrombocytosis, oral contraceptive, Trousseau’s syndrome in cancer patients, pregnancy, obesity, coagulation defect – Injury to blood vessels: abdominal surgery, trauma Sometimes causes death of patients whose operation had been successful; hence early mobilisation Massive emboli that saddle the bifurcation of pulmonary trunk or obstruct a main pulmonary artery are usually fatal Pulmonary thromboembolism: saddle embolus sitting at the bifurcation of pulmonary trunk Pulmonary thromboembolism involving main pulmonary artery of left lung  Complications of PTE Large PTE: Pulmonary trunk or one of its 2 branches. Death quickly occurs due to: – Right ventricular dilation bulging of IV septum into left ventricle left ventricular filling and LVF with circulatory collapse Pulmonary venous congestion Pulmonary oedema Intermediate PTE: Major branch of pulmonary artery within the lung. Pulmonary infarction (red infarction) Small multiple PTE: Arterioles and alveolar capillaries. Asymptomatic, pulmonary hypertension; may be followed by fibrinolysis  Autopsy Case - 1 40-year-old female. Present episode started 6 days ago with chest pain radiating to the back and incapacitating association with breathlessness on mild exertion. No cough, no fever, no leg swelling. There was associated orthopnoea, paroxysmal nocturnal dyspnoea, sweating, and palpitations. This morning after being helped to the toilet by the husband she became breathless, restless, sweating profusely. This continued till her death. Not a known hypertensive or diabetic but morbidly obese with a weight of 114kg Saddle thromboembolism: a large thromboembolus is sitting and obstructing the right ventricular outlet. (inverted horse rider) Saddle thromboembolism: both branches of the pulmonary artery have been opened to show thromboembolic occlusion Thromboembolus seen in the right ventricular outlet: a mass of coiled thrombus from the veins of the lower limb Thromboembolus: The mass has been uncoiled to reveal a thrombotic cast (with branching) of the veins of the lower limb from where it originated. Moderate atherosclerosis: atheromatous plaques on the aorta Gravid uterus: gestational sac in the lumen of the opened uterus Gravid uterus: 10-week-old foetus within gestational sac Corpus luteum of pregnancy seen in the right ovary of the patient  Autopsy report FUNDAMENTAL DISEASE Massive pulmonary thromboembolism CONCOMITANT ALTERATIONS Heart: Saddle thromboembolus in right ventricular outlet, pulmonary trunk and bifurcation of pulmonary artery. Lungs: Thromboembolic occlusion of the pulmonary artery on both lungs; pulmonary oedema; peripheral pulmonary infarcts on the right lung. Liver: Congestive hepatomegaly (2,250g). Kidneys: Ischaemic acute tubular necrosis. INDEPENDENT ALTERATIONS Heart: Cardiomegaly (350g); biventricular hypertrophy Liver: Fatty change (macrovesicular steatosis). Arteries: Atherosclerosis Ib (mild). CAUSE OF DEATH Acute cor pulmonale with cardiorespiratory failure  Discussion Were there any predisposing factors to thromboembolism in this patient? List them. What autopsy findings are consequent to the thromboembolism? Guess the length of time over which the patient had been having thromboembolism. Name 2 other predisposing factors to the development of thromboembolism.  Autopsy Case – 2 A 62-year-old male who presented with dyspnoea on exertion and recurrent cough both of 4 years; recurrent leg swelling of 2 years; and fever of 4 days. Patient was a known hypertensive, not compliant with medication. Examination reveals central cyanosis, coarse crepitations on all lung zones, tachypnoea. CNS: semi-conscious. Clinical diagnosis: hypertension, respiratory infection, chronic bronchitis. Observe: pulmonary (red) infarction - arrows; medium- sized thromboemboli within the pulmonary artery; atherosclerosis (yellow colouration) of the pulmonary artery; pulmonary oedema Arrow shows an adherent pale thromboembolus in arterial lumen Higher magnification Observe: Fibrinous exudate on the pleura and the depression of the lung periphery (arrows) – site of old infarction Cardiomegaly (750g) with left (1.8cm) and right (0.5cm) ventricular hypertrophy Calcified and ulcerated atheromatous plaques and thrombi on aorta Thromboembolus (arrow) within pulmonary artery Pulmonary thromboembolus within the atherosclerotic artery. Observe the lines of Zahn where the pale strips represent platelets and the darker stripes represent fibrin Lines Of Zahn Pulmonary infarction  Autopsy report FUNDAMENTAL DISEASES Heart failure secondary to systemic arterial hypertension Lobar pneumonia Pulmonary hypertension CONCOMITANT ALTERATIONS Heart: Cardiomegaly (750g); left (2cm) and right (0.5cm) ventricular hypertrophy; right and left heart failure Lungs: Lobar pneumonia; pulmonary oedema; extensive pulmonary thromboembolism with many new and old thromboemboli at various stages of organisation; fresh and old pulmonary infarcts Liver: Centrilobular congestion Arterial system: Atherosclerosis IIIb, pulmonary atherosclerosis CAUSE OF DEATH Cardiopulmonary failure  Discussion Which lesions predispose to pulmonary hypertension? What is the most obvious cause of thromboembolism here? What are the predisposing lesions to pulmonary infarction here? Briefly describe the pathogenesis of the pulmonary oedema. Can you explain all the symptoms and signs that the patient presented with? Adult respiratory distress syndrome (ARDS) aka diffuse alveolar damage (DAD) ARDS is an extreme form of acute lung injury associated with a variety of pulmonary and extrapulmonary insults Pulmonary insults infections (viral,bacterial) ,aspiration,toxin inhalation,oxygen therapy Extrapulmonary insults sepsis ,trauma (with hypotension) ,burns,pancreatitis, ingested toxins (e.g paraquat)  ARDS cont ARDS has multiple causes but the basic pathology is identical,irrespective of aetiology ARDS may occur as part of multiorgan failure Clinically the patient develops severe dyspnoea,marked hypoxemia with cyanosis and tachypnoea ,that is refractory to oxygen The latent period varies from several hours to days,during which the features are those of the underlying illness ARDS is associated with a high mortality  ARDS cont Pathogenesis The initial injury is to the capillary endothelium or the alveolar epithelium The endothelial damage is often initiated by endotoxin and is sustained by interactions between neutrophils, macrophages,cytokines (TNF,IL1,IL6 and IL8),oxygen radicals,complements and arachidonate metabolites Fluid and protein leak from the capillary into the alveoli Above events is complicated by interstitial or sometimes intra-avleolar fibrosis  ARDS cont Morphology Grossly the lungs are blue,heavy,haemorrhagic and oedematous, each weighing over 1kg Microscopically alveolar wall shows congestion, interstitial and intra-alveolar oedema,fibrin deposition,and diffuse alveolar damage the alveolar walls are lined by waxy hyaline membranes which are made up of fibrin-rich oedema fluids and lipid remnants of necrotic epithelial cells. Complication pulmonary fibrosis  Chronic obstructive pulmonary Chronic limitation ofdiseases air inflow into the lungs. The inflow is reduced by either of 2 reasons: – Increased resistance within the airways (normally due to stenosis) – Decreased pressure of expiratory flow (loss of pulmonary elasticity) Deaths in most patients with COPD is due to: – Respiratory acidosis and coma – Right-sided cardiac failure – Massive collapse of the lungs secondary to pneumothorax (ruptured bullae) The COPDs are: bronchial asthma, chronic bronchitis, bronchiectasis, and emphysema  Bronchial asthma This is the commonest cause of dyspnoea, cough, and wheezing Characterised by obstruction of the small airways by a combination of bronchospasms and mucous plugging, which fluctuates with time and is generally partially reversible with bronchodilators Affects about 10% of children and about 5% of adults 60% present as wheezy children (mild) and most of these mature to be asymptomatic adults  Types Extrinsic asthma: Initiated by a type I hypersensitivity reaction induced by exposure to an extrinsic antigen such as domestic dust, frying oil, freshly cut grass, pollen. There is positive family history of atopy Intrinsic (idiosyncratic) asthma: Initiated by diverse, nonimmune mechanisms including ingestion of aspirin, pulmonary infections especially viral, cold air, inhaled irritant gases such as smoke, sulphur dioxide, ozone, psychological stress, exercise. Exact mechanism is unknown. No family history of atopy  Pathology Bronchoconstriction due to smooth muscle hyperactivity and hypertrophy Hypersecretion of thick mucus with plugging of the small airways; the mucus contains IgE, Charcot- Leyden crystals, and Curschmann spirals; due to hypersecretion and hyperplasia of glands Oedema of the bronchial mucosa Inflammatory cell infiltration of bronchial mucosa by eosinophils (prominent), mast cells, lymphocytes, plasma cells, and macrophages Death in status asthmaticus results from thick mucous plugging and severe bronchoconstriction 1. Muscle hypertrophy 2. Muscle contraction 3. Gland hypersecretio n 4. Mucosal oedema 5. Inflammatory cell infiltrate 6. Epithelial necrosis 7. Thick mucous plug (E, Charcot- Leyden crystals, Curschmann Cut section of the lung in an 18-year-old male who died of status asthmaticus. Note the thick mucous plugs occluding 3 bronchi. Bronchiole of patient who died from status asthmaticus; note the thick plug occluding the lumen; inflamed wall Type I hypersensitivity reaction  Pathogenesis Most cases of asthma are mediated by a complex interplay of immunological mechanisms (type I hypersensitivity reaction) and inflammatory reactions Attacks are provoked by intrinsic and extrinsic factors Pre-sensitised IgE-coated mast cells: antigen stimulation with release of preformed products  Vascular permeability with oedema: PGD2, PGI2, PGE2, histamine, PAF, LT B4, C4, D4, E4 (SRS-A) Bronchoconstriction: SRS-A, histamine, PGD2 Mucous gland secretion: local peptides, SRS-A Leukocyte and E recruitment: SRS-A, IL-5, ECF-A  Bronchiectasis Abnormal and permanent dilatation of principal bronchi which is usually associated with infection Predisposing factors: – Interference in mucus drainage: obstruction (tumour, tuberculous lymphadenopathy and caseation), ↑mucus viscosity (cystic fibrosis), abnormality of ciliary movement ( Kartagener syndrome) – Necrotising or suppurating pneumonia infection (tubercle bacillus, staphylococci, mixed infections) Copious purulent sputum production with cough is the typical presentation Worse in the lower lobes because of gravitation of inhaled materials and secretions There is a hilar extraluminal tumour with intraluminal extension. This tumour will easily cause bronchiectasis Bronchiectasis: higher magnification shows the thickened (inflamed) bronchial wall around the dilated lumen Bronchiectasis: note the presence of fibrinous adhesions on the pleural surface Bronchiectasis Autopsy specimen of a 75- year-old male who died following 3 weeks of cough, haemoptysis, and breathlessness. The lower lobes show lobar pneumonia and bronchiectasis Bronchiectasis: dilated lumen containing purulent debris; inflamed wall; eroded epithelium  Complications of bronchiectasis Cor pulmonale Metastatic abscesses Systemic amyloidosis  Chronic bronchitis A functional disorder, defined clinically as ‘cough productive of sputum on most days for 3months of the year for at least 2 successive years’ Secretion of abnormal amounts of mucus, causing plugging of the airway lumen Hypersecretion is associated with hyperplasia of bronchial mucus-secreting glands Reid index (gland: wall thickness) is increased (>0.4) No inflammation; there may be associated squamous metaplasia Aetiology: habitual smoking, living in smog-laden city, and poorly controlled asthma in childhood Chronic bronchitis: note glandular hyperplasia, absence of inflammation. How does it differ from asthma? A normal bronchus (left) is compared with one with chronic bronchitis (right) Emphysema: Hyperinflated lungs; note the bullae on the surface. Bullae are large dilated airspaces that bulge out from beneath the pleura. Emphysema is characterized by a loss of lung parenchyma by destruction of alveoli so that there is permanent dilation of airspaces. Emphysema Emphysema: On cut section of the lung, the dilated airspaces of emphysema are seen. Emphysema involving upper field Emphysema: the loss of alveolar walls is demonstrated; remaining airspaces are dilated; compare with normal.  Emphysema Emphysema is a lung condition characterised by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, without obvious fibrosis There is decreased respiration in spite of ↑ventilation (breaths are rapid and shallow) Hypoxia and dyspnoea with mild exertion Loss of capillary bed and lung recoil (tidal volume) Causes – ↑protease (elastase) production by inflammatory cells, and from dead bacteria (smoking, pollution) – ↓protease inhibitors (alpha1-antitrypsin deficiency – cirrhosis, congenital deficiency)  Emphysema: Hyperinflated lungs; note the bullae on the surface. Bullae are large dilated airspaces that bulge out from beneath the pleura. Emphysema is characterized by a loss of lung parenchyma by destruction of alveoli so that there is permanent enlargement of airspaces. Emphysema Emphysema: On cut section of the lung, the dilated airspaces of emphysema are seen. Emphysema involving upper field Emphysema: the loss of alveolar walls is demonstrated; remaining airspaces are dilated; compare with normal. Dynamics of respiration in emphysema (compared with the normal) 50 40 End of inspiration 30 End of expiration 20 10 0 Normal Emphysema  Emphysema (2) START by explaining to me the mechanisms involved in the respiratory movements Strictly speaking, is it an obstructive disease (COPD)? NO. Because it involves the peripheral airways – respiratory bronchioles and beyond Why then is it classified as a COPD? Because there is limitation of airflow like in other obstructive diseases Why then is there limitation of airflow? Because it is always hyperinflated; the alveolar septa containing elastic tissue are destroyed, hence air is not pushed out of the lungs during expiration  Site Major Aetiology Clinical pathologic features change Chronic Bronchu Glandular Tobacco Cough, bronchiti s hyperplasia, smoke, air sputum s excess mucus pollutants production Bronch- Bronchu Airway Persistent Cough; iectasis s dilatation and or severe purulent scarring with infection sputum; pussy plugs fever Asthma Bronchu Smooth muscle Undefined Episodic s hypertrophy, or wheezing, glandular immunologi cough, hyperplasia, c causes dyspnoea excess mucus, inflammation (E) Emphyse Acinus Airspace Tobacco Dyspnoea ma enlargement; smoke,  Pneumonia Aka pneumonitis. Inflammation and consolidation of the lung Classified into lobar and bronchopneumonia depending on the pattern of involvement of the lung Lobar pneumonia involves the entire lobe and often more than one lobe; infection spreads through alveoli Bronchopneumonia involves scattered foci of lung parenchyma and is centred on bronchi; infection spreads through the bronchi Bronchopneumonia is a common cause of death and it typically develops in terminally ill patients, ancient people, and children  Pneumonia (2) Most bacteria that cause pneumonia are normal inhabitants of the oro- and nasopharynx and reach the alveoli by aspiration of secretions The commonest agent is Streptococcus pneumoniae, others are Staphylococcus, Haemophilus Predisposing factors to infection include smoking (sm), chronic bronchitis, alcoholism, severe malnutrition, wasting diseases, and poorly controlled diabetes, loss of cough reflex (coma, anaesthesia), accumulation of secretions (cystic fibrosis, tumour), exposure to cold Symptoms: fever, cough productive of sputum, pleuritic pain Pneumonia (3) Abscess Lobar pneumonia Bronchopneumonia Bronchopneumonia: The cut surface of this lung demonstrates the typical appearance of broncho- pneumonia with areas of tan-yellow consolidation. The areas of consolidation are firmer than the surrounding lung. Positive flotation test is noted Bronchopneumonia: The lighter areas correspond to areas of consolidation of lung parenchyma Bronchopneumonia Bronchopneumonia Lobar pneumonia involving the entire lobe on the right side Bronchopneumonia merging into lobar pneumonia Lobar pneumonia Pneumonia involving the left field and sparing the right field; the alveolar outline is still discernible on the left.  Pneumonia (4) The disease has 4 classical phases: – Congestion and oedema – Red hepatisation – Grey hepatisation – Resolution What is consolidation; what causes it? Is consolidation the same as hepatisation? Normal alveolus: empty (air filled) alveolar space; normal surrounding capillaries. “Enjoy it” Congestion or oedema: Numerous bacteria in alveolar space. Alveolar capillary congestion with exudation of plasma into alveolar space. Neutrophil margination but no emigration yet. Note pleura over lung surface. “Chei” Congestion of alveolar capillaries; pulmonary oedema; no cells in alveolar space Red hepatisation: RBCs predominate; some neutrophils and fibrin inside alveolar space. Lung is airless. Note the presence of a similar exudate under the pleura (pleural exudate). “Life is tough” Red hepatisation: numerous RBCs; some other cells present Red hepatisation: note abundance of erythrocytes Grey hepatisation: Predominance of fibrinopurulent exudate (neutrophils and fibrin); Pleural exudate. In the initial period only neutrophils predominate. “What will happen to me?” Grey hepatisation: Filling of space by inflammatory debris (neutrophils). Is this lesion likely to organise? Grey hepatisation: Neutrophils fill the alveolar lumen Grey hepatisation: congestion; this cellular exudate gives rise to the productive cough of purulent sputum – yellow, green, brown Grey hepatisation: Note congested capillaries in alveolar wall and the cellular debris rich in neutrophils within the alveoli Grey hepatisation Grey hepatisation: note paucity (near absence) of erythrocytes and predominance of fibrin and neutrophils Grey hepatisation: alveolar space is airless and filled with an amorphous eosinophilic material (fibrin) and neutrophils Grey hepatisation: Note the numerous basophilic bacterial rods present in the alveolar lumen Grey hepatisation: Note the numerous basophilic bacterial rods present in the alveolar lumen Resolution: Alveolar debris is clearing away. Pleural exudate has almost disappeared. “I think I’ll survive.” Resolution: note depletion of inflammatory exudate from the alveolar space; inspissated mucus Resolution: Complications of pneumonia Pleuritis with fibrinous exudate Pleural effusion Pyothorax, ±empyema Pulmonary fibrosis (destruction of parenchyma with organisation) Lung abscess (Staphylococcus) Septicaemia (±meningitis, bacterial endocarditis, septic arthritis) Deep vein thrombosis (elderly persons) Death Fibrinous exudate seen as a membranous film on pleura Pleural fibrinous exudate: What does it suggest? What is the pathogenesis? Bronchiectasis, pneumonia, fibrinous pleuritis: note the presence of fibrinous adhesions on the pleural surface Pulmonary abscess complicating bronchopneumonia: several pus-containing cavities are present. Pulmonary abscess: the alveolar walls have been destroyed; hence this lesion can only heal by cavitation and fibrosis  Atypical pneumonia Aka interstitial pneumonitis Inflammation here is in the alveolar septa and pulmonary interstitium; there is no exudate in the alveolar space Caused by viruses and Mycoplasma pneumoniae in majority of cases Histology: chronic inflammatory cells in alveolar wall and interstitium with pink hyaline membranes lining the alveolar walls Symptoms are milder and longer lasting than typical bacterial pneumonia Atypical pneumonia  Clinical case A 44-year-old male presented with cough of 11 years and haemoptysis of 2 years. He had been treated twice for pulmonary tuberculosis. Chest CT scan showed left lung collapse with significant mediastinal shift. Left pneumonectomy was done and specimen sent for pathology study. Clinical diagnosis: Destroyed lung syndrome Pathological findings: atelectasis, bronchiectasis, diffuse fibrosis, aspergilloma, lung abscess, pneumonitis, fibrinous pleuritis Note: shrunken lung (atelectasis); lung abcesses (yellow arrows); bronchiectasis (red arrows); aspergilloma (white arrow); scars Identify: Large lung abscess with dark pussy material within it; two bronchi with thickened brownish walls (bronchiectasis) Note: Aspergilloma with greenish-yellow content; fibrinous exudate on the pleura (fibrinous pleuritis)  Discussion Which of these is the patient prone to: pulmonary hypertension; pulmonary thromboembolism; cor pulmonale What category of atelectasis will be seen here? Describe the pathogenesis of the bronchiectasis. What is the fundamental disease?  Pneumoconioses Pulmonary disease caused by inhalation of inorganic dusts,aerosols,organic dusts,fumes and vapors In normal persons, dusts >5µ are trapped in URT (up to 1o bronchi); 1pack per day Passive smokers 2X have increase in risk Exposure to industrial carcinogens (asbestos, radioactive material [uranium], nickel, chromium, iron oxides)  Presentation Pulmonary symptoms: cough, haemoptysis, pulmonary infections (including abscess), atelectasis, bronchiectasis Superior vena cava syndrome: venous congestion of upper part of body Pancoast syndrome: lower brachial plexus damage (C8- T2); shoulder pain radiating along the distribution of ulnar nerve. May damage cervical sympathetic nerves and result in Horner’s syndrome (enophthalmos, ptosis of upper eyelid, miosis, anhidrosis on affected side) Paraneoplastic syndromes: Cushing’s syndrome (ACTH), hyponatremia (ADH), gynaecomastia (E), finger clubbing (pulmonary hypertrophic osteoarthropathy), hypercalcaemia (PTH), general (cachexia, anorexia, fever, immunodepression), haematological (DIC, anaemia, thrombophlebitis migrans). Ptosis is a drooping of the upper lid.  Histological types Squamous cell carcinoma – Injury to respiratory epithelium successively causes squamous metaplasia, dysplasia, and invasive squamous cell carcinoma – Most arise in central portion of lung from major or segmental bronchi – There are invasive columns, islands, and cords of atypical squamous cells with variable cytological atypia, necrosis, and haemorrhage Adenocarcinomas (most common) – Tends to arise in the periphery, usually upper lobes – There are invasive glands lined by atypical cells – Occurs more often in non-smokers and former smokers  Histological types cont Small cell lung carcinoma extremely responsive to chemotherapy Large cell carcinoma diagnosis of exclusion where no other histologic type is present Bronchioloalveolar carcinoma here the tumour cells spread along the alveolar walls without invading the underlying stroma. Currently, it is called adenocarcinoma in situ (a precursor lesion) n/b that two or more histological types may be found in a patient (histological heterogeneity) Carcinoid tumours a low grade malignant neuroendocrine tumour are also seen  Benign & peculiar lung tumours Mesenchymoma ( formerly known as bronchial hamartomas) it consists of cartilage ,bone,fat, loose mxyoid tissue and islands of ciliated epithelium papilloma of the Bronchus Langerhans’ cell Histiocytosis  Secondary lung cancer The most common malignant neoplasm of the lung is a metastatic tumour Typically multiple and circumscribed – “cannon ball” metastases Primary lung carcinoma located in the hilum. It compresses the right principal bronchus and deviates the trachea. What are the possible complications of this tumour in the lung parenchyma? What is the most probable histological type? Primary lung carcinoma: This is a more advanced lesion. There is a cavity in the lower portion. Necrosis and haemorrhage are not rare events in carcinomas. Squamous cell carcinoma: Irregular invading columns, islands and cords of atypical squamous cells; there is no glandular pattern Lung adenocarcinoma: Solitary tumour at the periphery. Adenocarcinoma: irregular invasive glands and cords Metastatic lung carcinoma: Multiple tan nodules all over lung parenchyma. “Cannon ball metastasis.” The multiplicity suggests that this is a secondary tumour. Observe the hilar lymph node invaded also by metastatic tumour. Metastatic lung carcinoma: Aka “cannon ball metastasis.”  pleura Pleural effusion is a common problem detected clinically when approximately 500ml is present Effusion is categorized as a transudate or exudate Normal pleural fluid has a protein concentration of 0.4g/dL A transudate has a protein concentration 30g/L ; it is due to imflammatory or neoplastic processes, where vascular permeability is increased  Pleura cont Empyema is collection of pus in the pleural cavity usually secondary to an underlying pneumonia, sometimes due to a stab wound to the chest or rarely post-thoracic surgery Haemothorax ,a collection of blood,follows thoracic trauma or ruptured thoracic aortic aneuryms Chylothorax , is a collection of opalescent lymph, usually due to obstruction of thoracic duct,typically by tumour Pneumothorax is an accumulation of air in the pleural space is commonly caused by rupture of an emphysematous bulla,but may also follow penetrating chest wall injuries  Pleura cont Pleurisy is an imflammation of the pleura usually due to infections Malignant Mesothelioma is the most commonest tumour and is due to exposure to asbestos exposure in most cases The disease may occur in the pleura,peritoneum or rarely the pericardium The disease is rare before 40 and shows a male preponderance Patients present with dyspnoea,pleural effusion,chest pain,weight loss,cough and fever. Most patients are dead within a year  Pleura cont Morphology : it is usually unilateral,starting as a small nodule over the visceral pleura and extending to cover the entire lung Microscopically these tumour are divided into epitheloid,sarcomatoid and mixed