RESPIRATORY SYSTEM

BRONCHIECTASIS
 
2.    What are the gross morphological features of the condition?
 
a.    Cystic, smooth, glistening appearance of cut surface.
b.    Bronchi are grossly dilated, some with saccular outpouchings.
c.    Intervening lung tissue is reduced and fibrosed.

3.    What are the clinical manifestations of the condition?
 
a.    Fever.
b.    Cough with production of abundant purulent sputum.
c.    Dyspnoea
d.    Pleuritic chest pain.

4.    What are the complications associated with the condition?
 
a.    Hemoptysis.
b.    Chronic suppuration leading to lung abscess and broncho-pleural fistula formation.
c.    Septic emboli to the brain leading to brain abscess or meningitis.
d.    Destruction of lung parenchyma leads to pulmonary hypertension and cor pulmonale. 

5.    What are the histological features?
 
·         Capillary congestion, interstitial & intraalveolar edema & hemorrhage. 
·         Alveolar ducts are dilated & alveoli tend to collapse. 
·         Hyaline membranes lining distended alveolar ducts. 
·         Marked distortion of lung parenchyma with diffuse interstitial fibrosis.
 
6.    What are the chest X-ray findings?
 
a.    Cystic shadows.
b.    Fluid levels in the lungs.
c.    Thickened bronchial walls.

7.    What is the pathogenesis of this condition?
 
a.    Main mechanism is by recurrent inflammation of the lungs due to unresolved infections, obstruction of a proximal airway by tumor, foreign body causing retention of secretions.
b.    Destruction of elastic tissues, muscle and cartilage leads directly to bronchial dilatation.
c.    Spread of infection to pleura causes adhesions and fibrosis of pleura; contraction of fibrous tissues results in bronchial dilatation.
d.    Chronic coughing as a result of the pulmonary infection leads to a rise in bronchial pressure during inspiration with resultant expansion of bronchi.

LUNG ABSCESS

2.    What are the gross morphological features of the condition?
 
a.    Creamy yellowish-white lesion diffusely scattered throughout the lung.
b.    Shaggy appearance with irregular poorly defined edges.
c.    Dilation of some bronchi.
d.    Patchy fibrosis of lung parenchyma.

3.    What are the clinical manifestations of the condition?
 
a.    Swinging fever.
b.    Cough with production of abundant purulent sputum.
c.    Dyspnoea
d.    Pleuritic chest pain.
e.    Hemoptysis.

4.    What are the complications associated with the condition?
 
a.    Subpleural abscesses may extend to pleural cavity to cause empyema.
b.    Septic emboli to the brain leading to brain abscess or meningitis.
c.    Erosion of large pulmonary vessel leading to fatal hemorrhage. 

5.    What are the possible causes?
 
a.    Inhalation of infective material from larynx or pharynx.
b.    Aspiration of stomach contents, e.g. alcoholics, coma.
c.    Obstruction of a bronchus by tumor growth or foreign body.
d.    Infection of pre-existing cavities, e.g. in TB or bronchiectasis.
e.    Pneumonia: abscess is most likely to occur in debilitated patients with bronchopneumonia.
f.    Septic emboli from subacute bacterial endocarditis, septicaemia and IV drug abuse.
g.    Spread of subphrenic / hepatic abscess. 

BRONCHOPNEUMONIA

This lung is taken from a 80-year-old lady who died of an unknown respiratory infection at a nursing home.

1.    What are the gross morphological features of the condition?
 
a.    Patchy consolidation of the lung: firm and airless. 
b.    Large, irregular-shaped lesions, reddish-yellow in color, ranging from 2 - 6 cm in diameter, with ill-defined margins. 
c.    Pleura is thickened.
d.    Patchy fibrosis of lung parenchyma.

2.    What is your diagnosis and how does it cause the above mentioned pathological features?
 
Bronchopneumonia. In bronchopneumonia, primary infection centered on bronchi spreads to involve adjacent alveoli, which become filled with an acute inflammatory exudate, and affected areas of the lung become consolidated. Initially, consolidation is patchy within the lung, but, if untreated, it becomes confluent leading to lobar pneumonia.

 
3.    Which age group does it affect the most?
 
Bronchopneumonia is most common in infancy and old age, is predisposed by the presence of debility and immobility. Patients who are immobile develop retention of secretions; these gravitate to the dependent parts of the lungs and become infected, hence bronchopneumonia most commonly involves the lower lobes. 

4.    What are the common pathogens?
 
Staphylococci, streptococci, pneumococci, Haemophilus influenzae, Pseudomonas aeruginosa and the coliform bacteria. 

5.    What are the complications?
 
a.    Tissue destruction and necrosis, causing abscess formation (particularly common with Klebsiella infections).
b.    Spread of infection into the pleural cavity, causing empyema.
c.    Organization of the exudate which converts a portion of the lung into solid tissue.
d.    Bacteremic dissemination to the heart valves, pericardium, brain, kidneys, spleen, or joints, causing metastatic abscesses, endocarditis, meningitis, or suppurative arthritis. 

6.    If this patient has swallowing difficulties due to a stroke, what might you suspect? Is it possible based on your pathological findings?
 
The pneumonia is caused by aspiration into the airway due to impaired swallowing. Gastric acid causes chemical pneumonitis, which can lead to adult respiratory distress syndrome. 
 
It is unlikely as aspiration pneumonia will usually give rise only to a few lesions in the right middle lobe of the lung. 

LOBAR PNEUMONIA

1.    What are the gross morphological features of the condition?
 
Widespread fibrinosuppurative consolidation of the lower lobe of the right lung. Consolidated area is firm, gray, and airless. 

2.    What is your diagnosis and how does it cause the above mentioned pathological features?
 
Lobar pneumonia. In lobar pneumonia, organisms gain entry to distal air spaces rather than colonizing bronchi. Rapid spread through the alveolar spaces and bronchioles causes acute inflammatory exudation into air spaces. 

3.    Which age group does it affect the most?
 
Lobar pneumonia is seen in adults. Vagrants and alcoholics who have poor social and medical care are particularly prone to this pattern of pneumonia, which is often caused by Pneumococcus or Klebsiella.

4.    What is the prognosis?
 
Patients with lobar pneumonia are usually severely ill, and there is usually associated bacteremia. If treated promptly, many patients recover with the lungs returning to normal function and structure by resolution. In other cases the exudate in alveoli is organized, leading to lung scarring and permanent lung dysfunction. Common complications are development of pleurisy, lung abscess, and septicaemia.

5.    How do you differentiate this from bronchopneumonia?
 
a.    Areas affected: uniform consolidation (lobar) versus patchy consolidation (bronchopneumonia).
b.    Persons affected: immunocompetent (lobar) versus immunocompromised (bronchopneumonia).
c.    Lobar pneumonia has few complications with complete resolution while bronchopneumonia has more complications and often incomplete resolution.

6.    Describe the stages of inflammatory response histologically.
 
a.    Congestion: vascular engorgement, intra-alveolar fluid with few neutrophils and presence of numerous bacteria.
b.    Red hepatization: massive confluent exudation with red cells and neutrophils and fibrin filling the alveolar spaces.
c.    Gray hepatization: progressive disintegration of red cells and persistence of the fibrino-suppurative exudate.
d.    Resolution: consolidated exudate is digested to produce a granular, semifluid debris that is resorbed. 

PRIMARY GHON COMPLEX

1.    What is the lesion shown? Describe its features.
 
Primary Ghon complex. It consists of a 1- to 1.5cm area of gray-white consolidation, with the presence of central caseous necrosis at the hilum. The parenchymal focus is present in the lower left subpleural location. Lymph nodes with caseation are visible in the upper right. 

2.    How is it formed and what does it consist of?
 
When infection with TB first occurs, e.g. in childhood, the organisms are inhaled and come to proliferate in alveoli at the periphery of the lung, often just beneath the pleura. Although organisms are of low intrinsic pathogenicity, they cause cell death in adjacent lung. An ineffective acute inflammatory response occurs, which fails to destroy bacteria. Bacteria are then conveyed to local nodes at the lung hilum, where they also proliferate. After about 3 weeks, an immune response develops, and activated T-cells recruit macrophages to the lung and nodes, with resulting granulomatous inflammation and caseation resulting in a Ghon complex.
 
The Ghon complex consists of:
 
a.    A parenchymal subpleural lesion, often just above or just below the interlobar fissure between the upper and lower lobes.
b.    Enlarged caseous lymph nodes draining the parenchymal focus. 

3.    What is the usual clinical course?
 
In the vast majority of cases the Ghon focus and caseating granulomas in the lymph nodes heal by the deposition of collagen around the tubercles. 
 
The healed lesion comprises an area of central caseation surrounded by a wall of dense collagen with frequent deposition of calcium salts. 
 
The patient is sensitized to the organism and becomes acquire resistance to it. The disease does not progress, because the organisms are confined within the shell of collagen. 
 
However:
 
1.    The foci of scarring may harbor viable bacilli for years and thus be the nidus for reactivation at a later time when host defences are compromised.
 
2.    Uncommonly, the disease may develop without interruption into progressive primary TB. The primary focus enlarges, caseates, and cavitates, sometimes spreading through the airways or lymphatics to multiple sites within the lung or causing multiple patchy white areas of cheesy consolidation that may cavitate. Blood-borne dissemination may give rise to miliary TB.

4.    Which group of people are predispose to this condition?
 
Malnourished, immunocompromised, alcoholics and those with intercurrent disease such as diabetes, chronic lung disease, and Hodgkin's disease.

5.    What is the pathogenesis?
 
Mycobacteria are acid-fast obligate bacilli. Transmission is usually direct, by inhalation of airborne organisms in aerosols generated by expectoration or by exposure to contaminated patient secretions.
 
Once in the lung, the mycobacteria are phagocytosed by macrophages. However they are not destroyed; the mycolic acid in their cell walls make them resistant to degradation and accounts for their virulence. 
 
The antigen from the tubercle bacillus is presented together with class II MHC complex on the macrophage membrane which reaches draining lymph nodes and is presented to T cells. T cells are sensitized and recirculate to the site of infection. Secretion of cytokines by T cells, particularly gamma-interferon recruit and activate monocytes to kill or inhibit the growth of the organism.
 
In response to the cytokines and constituents of the bacillus cell wall, some of the activated macrophages form granulomas which subsequently entrap the microorganisms thereby walling them off from the normal healthy tissues and limiting the spread of the inflammatory process.
 
A granuloma consists of a central area of amorphous caseous necrosis surrounded by a zone of activated macrophages, in which multinucleate macrophages (Langhan's giant cells) are present. There are outer layers of lymphocytes and fibroblasts.

6.    How can you detect the presence of this condition in a patient? What can cause false negative results?
 
Infection, whether active or inactive, can be detected by the tuberculin (Mantoux) test, which reveals the development of skin sensitivity to tuberculoprotein. 
 
About 2 - 4 weeks after the infection has begun, IV injection of 0.1ml of purified protein derivative (PPD) induces a visible and palpable induration (at least 5mm in diameter) that peaks in 48 to 72 hours. The test is positive if it produces > 10mm induration, and negative if < 5mm.
 
A positive tuberculin test result signifies the presence of cell-mediated hypersensitivity to tubercular antigens. However, it does not differentiate between infection and disease.
 
False negative reactions may be produced by certain viral infections, sarcoidosis, malnutrition, Hodgkin's disease, immunosuppression and overwhelming active tuberculous disease.
 
False positive reactions may also result from infection by atypical mycobacteria.

SECONDARY PULMONARY TB

1.    What is the lesion shown? Describe its features.
 
Secondary pulmonary TB. Multiple yellowish-white lesions with ill-defined edges scattered throughout the lung parenchyma, some with central cavitation.

2.    How is it formed?
 
Secondary TB is the pattern of disease that arises in a previously sensitized host. It may follow shortly after primary TB but more commonly it arises from reactivation of dormant primary lesions many decades after initial infection, particularly in those with weakened host resistance.
 
Secondary pulmonary TB is usually located at the apex of one or both upper lobes. The initial lesion is a small, focus of consolidation, less than 2cm in diameter, located within 1 to 2cm of the apical pleura. 
 
As the lesion enlarges with expansion of the area of caseation, it erodes into a lymph channel, releasing the organisms into the lymph ducts, which empty into the venous return to the right side of the heart and into the pulmonary arteries from which it spreads throughout the lung parenchyma.

3.    What is the usual outcome of the lesions described?
 
The lesions may expand and coalesce to yield almost total consolidation of large regions or even whole lobes of the lung. With chronicity, secondary scarring may markedly distort the pulmonary architecture. With progressive pulmonary TB, the pleural cavity is involved, and serous pleural effusions, tuberculous empyema or obliterative fibrous pleuritis may develop.

4.    How can it spread to other parts of the body and which organs are commonly affected?
 
Systemic miliary TB ensues when infective loci in the lungs seed the pulmonary venous return to the heart; the infection subsequently disseminates through the systemic arterial system. Almost every organ in the body may be seeded. It is most prominent in the liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes, and epididymis. 

4.    What are the atypical signs if the patient has AIDS as well?
 
a.    Mantoux tests may be falsely negative.
b.    There is increased reactivation of latent TB.
c.    Presentation may be atypical.
d.    Atypical CXR: lobar or bibasilar pneumonia, hilar lymphadenopathy.
e.    Extra-pulmonary and disseminated disease much more often.

5.    What are the clinical manifestations?
 
a.    Insidious fever.
b.    Night sweats.
c.    Weight loss.
d.    Productive cough with blood-streaked sputum.
e.    Hemoptysis.

6.    How would you diagnose it in a laboratory?
 
Acid-fast (Ziehl-Neelsen stain) staining of sputum will turn red in the presence of mycobacteria.

7.    What are the first-line drugs you would use to treat this condition?
 
Isoniazid, rifampicin and pyrazinamide for 9 months while ethambutol is used for 6 months. 

EMPHYSEMA

This is the lung of a 73-year-old man with a 5-year-history of chronic obstructive lung disease

1.    What is the lesion shown? Describe its features.
 
Emphysema. The lung is voluminous, hollowy and airy, giving a honey-combed appearance. 

2.    What are the histological features?
 
a.    Destruction & fusion of alveoli gives rise to large air spaces.
b.    Distortion of pulmonary parenchyma with compression of vessels and bronchioles. 

3.    What is the pathogenesis?
 
The pathogenesis of emphysema is thought to be parenchymal destruction, including the alveolar walls, by secreted extracellular proteases, normal defensive protease inhibitors being either inactivated or absent.

4.    How does smoking predisposes to this condition?
 
Smoking leads to increased protease activity and decreased activity of protease inhibitors:
 
a.    Cigarette smoke deposited in terminal bronchioles stimulates release of neutrophil chemotactic factors by activated alveolar macrophages.
b.    Nicotine itself is chemotactic for neutrophils.
c.    Smoking stimulates the release of elastase from neutrophils.
d.    Smoking enhances elastolytic protease activity in macrophages.
e.    Oxidants in cigarette smoke and oxygen free radicals secreted by neutrophils inhibit alpha-antitrypsin activity. 

5.    What investigations would you do to confirm your diagnosis?
 
a.    CXR: hyperinflation > 6 anterior ribs seen above diaphragm in mid-clavicular line, flat hemidiaphragms, large central pulmonary arteries, reduced peripheral vascular markings, bullae.
b.    Lung function tests: FEV1 / FVC < 70%; increased residual volume and total lung capacity.
c.    FBC: secondary polycythaemia.

6.    What are the possible causes of death in this patient?
 
a.    Respiratory acidosis and coma.
b.    Right-sided heart failure.
c.    Massive collapse of the lungs secondary to pneumothorax.

BRONCHOGENIC CARCINOMA

This is the lung of a 74-year-old man who first presents with cough, chest pain, wheezing,  hemoptysis and worsening dyspnea.

1.    What is the lesion shown? Describe its features.
 
Bronchogenic carcinoma. Fungating, hard solid white mass arising from the bronchial lining invading into the left bronchus and surrounding tissues. 

2.    Relate the pathology to the clinical features.
 
a.    Cough: infection distal to airway blocked by tumor.
b.    Hemoptysis: ulceration of tumor in bronchus.
c.    Dyspnoea: local extension of tumor.
d.    Chest pain: involvement of pleura and chest wall.
e.    Wheeze: narrowing of airway.

3.    What complications can arise?
 
a.    Pneumonia, abscess and lobar collapse due to tumor obstruction of airway.
b.    Dysphagia due to diaphragm paralysis secondary to phrenic nerve invasion.
c.    Pleural effusion due to spread of tumor into pleura.
d.    Recurrent laryngeal nerve palsy leading to hoarseness of voice.
e.    Horner's syndrome due to involvement of cervical sympathetic ganglia by Pancost tumor.
f.    Brachial neuritis.
g.    Pericarditis.
h.    Superior vena caval syndrome.

4.    The patient also complains of muscle ache throughout the body. What is this due to and what are the other possible symptoms?
 
This is a paraneoplastic syndrome not stemming from the local growth or distant spread of the tumor.
 
Other paraneoplastic syndromes are:
 
a.    SIADH: ADH secretion.
b.    Cushing syndrome: ACTH secretion.
c.    Hypercalcaemia: elaboration of a PTH-related peptide.
d.    Neurological: peripheral neuropathy, cerebellar degeneration, dermatomyositis, Lambert-Eaton myasthenic syndrome, proximal myopathy.
e.    Hypertrophic pulmonary osteoarthropathy.
f.    Acanthosis nigricans.

5.    What are the various methods you can use to come to a conclusive diagnosis of the nature of the lesion?
 
a.    Sputum cytology: examination of expectorated sputum by cytology.
b.    Cytology of pleural effusion.
c.    Percutaneous needle aspiration under image guidance to obtain cytological preparation.
d.    Bronchoscopy and biopsy: small tumor biopsy obtained.

6.    What is the molecular pathology of this lesion?
 
Bronchogenic carcinoma is characterized by multiple genetic alterations:
 
a.    Inactivation of tumor suppressor genes, e.g. RB and p53.
b.    Activation of dominant oncogenes, e.g. ras proteins.
c.    Overexpression of epidermal growth factor receptor. 

7.    How would you stage it?
 
Primary tumor (T):
 
TX: malignant cells in bronchial secretions, no other evidence of tumor.
Tis: carcinoma in situ.
T0: none evident.
T1: < 3cm, in lobar or more distal airway.
T2: > 3cm, and > 2cm distal to carina or any size if pleural involvement or obstructive pneumonitis extending to hilum, but not all the lung.
T3: involves the chest wall, diaphragm, mediastinal pleura, pericardium or < 2cm from, but not at, carina.
T4: involves the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina or a malignant effusion is present. 
 
Regional nodes (N):
 
N0: none involved (after mediastinoscopy).
N1: peribronchial and / or ipsilateral hilum.
N2: ipsilateral mediastinum or subcarinal.
N3: contralateral mediastinum or hilum, scalene, or supraclavicular.
 
Distant metastasis (M):
 
M0: none.
M1: distant metastases present.     
 
a.    Respiratory acidosis and coma.
b.    Right-sided heart failure.
c.    Massive collapse of the lungs secondary to pneumothorax.