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FACULTY OF NURSING

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Topic 1: INTRODUCTION AND REVIEW OF THE RESPIRATORY SYSTEM ANATOMY

 Respiration is the process by which O2 is transported to and used by cells, and CO2 produced is eliminated from the body, a task effectively carried out by the cooperative work of the respiratory system, red blood cells and the circulatory system. Oxygenation of blood and elimination of CO2 is called external respiration while utilization of O2 by cells and production of CO2 by the cell is described as internal respiration or cellular respiration. Most cells in the human body require O2 for survival and to carry out their functions. During their normal processes of work the cells use up O2 and produce CO2 as a waste product that must be eliminated from the body.

 The normal intake of air is 7 litres/min of which 5 litres is available for alveolar ventilation. The definite flow is maintained from the point of entry up to the terminal bronchiole after which the flow ceases and allows gas exchange to take place. The factors that maintain adequate respiration include adequate intake of air, rapid diffusion along the alveolar ducts and through alveolar walls and adequate perfusion. In chronic lung disease, ventilation, diffusion and perfusion disorders are present in varying degrees. Under normal circumstances the upper area of the lung is better ventilated than perfused while the base is better perfused than ventilated an imbalance magnified in lung disease.

 REVIEW OF ANATOMY OF RESPIRATORY SYSTEM

 The respiratory system comprises of lungs and respiratory passages (airways), which work in intimate collaboration with the thoracic cage, respiratory muscles and the pulmonary circulation.

 Respiratory physiology is a complex series of interacting and coordinated processes that ensure adequate and prompt supply of oxygen and removal of carbon dioxide in an effort to maintain the stability and consistency of the internal environment.  It takes on board physiological control mechanisms such as acid-base, water and electrolyte balance, circulation and metabolism.

 The lungs are the structures where gas exchange between blood and inspired air takes place whereas the respiratory passages are the structures along which air is conveyed to and from the lungs. The passages include the nasal cavities, nasal pharynx, mouth, oral pharynx, larynx, the trachea, bronchi, bronchioles, terminal bronchioles, respiratory bronchioles and alveolar ducts. It is important to note that usually the bronchi and bronchioles are imbedded in the structure of the lung substance.

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Topic 1: DIVISIONS OF THE RESPIRATORY SYSTEM

DIVISION OF RESPIRATORY SYSTEM

 The respiratory system is divided into upper and lower tracts or divisions. Organs of the upper respiratory tract are located outside the thorax or chest cavity whereas those in the lower division are located almost entirely within the chest.

 1)      The Upper Respiratory Tract

    1. Nose
    2. Pharynx
    3. Nasopharynx,
    4. Oropharynx
    5. Laryngopharynx
    6. Larynx
    7. Trachea

2)      Lower Respiratory Tract

    1. Bronchial tree
    2. LungsRespiratory system

ORGANIZATION OF RESPIRATORY SYSTEM

The respiratory system comprises of lungs and respiratory passages (airways), which work in intimate collaboration with the thoracic cage, respiratory muscles and the pulmonary circulation. It uses highly effective convective systems of ventilation and circulation for long distance transport of O2 and CO2 and uses diffusion exclusively for short distance movements of O2 and CO2.

 The main components of the respiratory system are: - the air pump, mechanism for oxygen and carbon dioxide carrying, gas exchange surface, circulatory system and regulatory mechanisms.

FUNCTIONS OF THE RESPIRATORY SYSTEM;

  1. Provide oxygen to the blood stream and remove carbon dioxide
  2. Enables sound production or vocalization as expired air passes over the vocal cords
  3. Assists in abdominal compression during micturation (urination), defecation and parturition (childbirth)
  4. Lung Defence mechanism - protective and reflexive non-breathing air movements e.g. coughing and sneezing to keep the air passageways clean.
  5. Temperature regulation – loss of heat during expiration
  6. Maintenance of water balance   - small amounts of water are lost during expiration
  7. Regulation of acid-base balance
  8. Anticoagulant function – lungs contain mast cells which secret heparin which prevents intravascular clotting 
  9. Metabolic functions – manufacture surfactant for local use, fibrinolytic system
  10. Endocrine functions

Endothelial cells of the pulmonary capillaries secrete angiotensin converting enzyme  (ACE) which activates angiotensin I into angiotensin II

Lung tissues synthesize prostaglandins, acetylcholine, bradykinin and serotonin 

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Topic 1: INTRODUCTION TO RESPIRATORY PATHOLOGIES

healthcare organisationsINTRODUCTION TO PATHOLOGY OF THE RESPIRATORY SYSTEM

 The prime role of the respiratory system is oxygenation of blood and removal of carbon dioxide CO2. This function requires that air is brought into close approximation with blood which is provided by the anatomical arrangement of the alveoli and blood vessels. 

  1. Constant inward and outward flow of the enormous air exposes the respiratory system to infection by both microbes present in inspired air and by downward spread of bacteria that colonize the nose and throat
  2. Inhalation of pollutants such as dust, fumes, smokes increase the incidence of bronchitis, chronic lung disease and bronchial carcinoma
  3. Vascular architecture of the lungs allows passage of blood into the lungs during each cycle makes the lungs to be vulnerable to effects of cardiovascular diseases. This is due to disturbance of pulmonary haemodynamics e.g. pulmonary oedema and on the other hand, lung diseases interfere with the pulmonary blood flow with noticeable effects on the heart and systemic circulation because cardiac and pulmonary functions are closely interdependent.
  4. The lung is a frequent victim of malfunction elsewhere for example failure of the left side of the heart results in pulmonary congestion and oedema, systemic thrombosis on many occasions causes pulmonary embolism and the lungs are a common site for secondary tumours. 

 The main diseases of the airways and the lungs are caused by infection and inflammation with environmental factors such as smoking and occupational exposure to dust contributing to the morbidity and mortality resulting from respiratory problems. Tumours of the bronchial tree and lung are common and important, as almost all of them are malignant.  The key effect of respiratory problems is poor oxygenation resulting in respiratory failure.

CONDITIONS OF RESPIRATORY SYSTEM

  1. Congenital Disorders
  2. Paediatric lung disease - Hyaline membrane diseases (RDS)
  3. The Upper Respiratory Tract
    1. Inflammatory conditions - Coryza , Rhinitis, Sinusitis, Pharyngitis , Laryngitis, Epistaxis
    2. Tumours (benign and malignant)
  4. Respiratory failure
  5. Lung Collapse and Atelectasis 
  6. Obstructive Pulmonary Diseases (Acute and chronic bronchitis, Bronchiolitis, Bronchial asthma, Bronchiectasis, Bronchial obstruction, Emphysema)
  7. Pulmonary Infections
  8.  Pneumonias
    1. Bacterial (Lobar pneumonia, Bronchopneumonia, Staphylococcal pneumonia, Klebsiella pneumonia)
    2. Viral
    3. Mycoplasmal
  9. PCP
    1. Atypical
    2. Aspiration
    3. Hypostatic
  10. Fungal infections
  11. Lung abscess
  12. Empyema
  13. Pulmonary tuberculosis
  14. Pulmonary infections in HIV/AIDS
  15. Restrictive Pulmonary Disease
    1. Immunological pulmonary disease - Bronchial asthma, Allergic pneumonitis and Good Pasture’s Syndrome
    2. Pneumoconiosis
    3. Collagen – Vascular disease
    4. Pulmonary Fibrosis
  16. Pulmonary vascular disease
    1. ARDS
    2. Pulmonary hypertension
    3. Pulmonary oedema
  17. Acute Lung Injury
  18. Drug and toxin injury of the lungs
  19. Tumours 
  20. Pleura
    1. Pleural effusion
    2. Pneumothorax
    3. Tumours

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Topic 1: Summary

  1. The functions of the respiratory system include;
    1. Passageway for inhaled or exhaled air.
    2. Warming/cooling and humidifying inhaled air.
    3. Purification of inhaled air.
    4. Sensory organ of smell.
  2. Respiratory system conditions include;
    1. Congenital disorders of the respiratory system.
    2. Infections.
    3. Obstructive and restrictive airway diseases.

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Topic 1: References

  1. Kishasha M (2016). Textbook of human pathology. 1st edition, Acrodile publishers, Nairobi, Kenya.
  2. Harsh M (2014). Textbook of Pathology. 1st edition. New Delhi: Jaypee Brothers, Medical Pub, India
  3. Ngton C, & Muir (2014). Textbook of Pathology. 15th edition, New Delhi. Jaypee Brothers, India
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Topic 2: PAEDIATRIC LUNG DISEASE (DEVELOPMENTAL ANOMALIES)

Developmental Abnormalities

Developmental defects of the lungs include;

  1. Agenesis or hypoplasia of both lungs, 
  2. One lung or single lobe; 
  3. Tracheal and bronchial anomalies – atresia, 
  4. Stenosis and tracheobronchial fistula; 
  5. Vascular anomalies; 
  6. Congenital lobar over-inflation (emphysema), 
  7. Broncogenic cysts ; congenital airway malformation and pulmonary sequestrations

 PULMONARY HYPOPLASIA 

  1. Incomplete development of both lungs resulting in reduced weight, volume and acini compared to body weight and gestational age
  2. Lung smaller than normal
  3. Incidence 10%
  4. Associated with other congenital abnormalities and lung compression by abnormal masses and oligohydramnious
  5. Usually secondary to space occupying lesion  in the uterus, oligohydromnious or impaired foetal respiratory movements as seen in congenital diaphragmatic hernia, renal cystic kidney, renal agenesis and ancephaly. 

BRONCHIAL ATRESIA

Results in severe narrowing of the bronchus

 BRONCHOGENIC SEQUESTRATION 

  1. Cysts attached to the trachea
  2. Represent accessory bronchial buds

BRONCHOGENIC SEQUESTRATION

  1. Patients develop abnormal lung mass without any normal connection to the airway or bronchial system
  2. There are two types of sequestration – extralobular and intralobular
  3. Extralobular sequestrations – external to the lungs and found elsewhere in the thorax and mediastinum
  4. Intralobular sequestrations – found in the lung tissue and usually associated with recurrent localized infections or bronchiectasis

 Neonatal Respiratory Distress Syndrome (Hyaline Membrane Disease)

 Introduction

  1. Due to deficiency of surfactant (
  2. Primarily disease of premature infants
  3. Seen in infants of diabetic mothers (excess insulin production by the foetus suppresses surfactant production)
  4. Gestation 32 – 36 weeks 20% mortality
  5. < 28 weeks – 60% mortality

Risk Factors

  1. Prematurity
  2. Diabetic mother
  3. Neonatal aspiration
  4. Multiple births

 Pathogenesis

 Immature or damaged lung is unable to make enough surfactant (a lecithin-rich surface-active lipid) that reduces surface tension in the alveoli and keeps the alveoli open. Lack of surfactant results in lung collapse with microatelectasis.

 Hypoxia causes damage to the alveolar lining cells and pulmonary arterial constriction resulting in endothelial damage hence plasma leaks into the alveoli where it is deposited as fibrin (bright pink-stained membrane) and thus the name hyaline membrane disease. Fibrin reduces gas exchange further worsening the hypoxic state.   

 Pathogenesis of ARDS

RISK FACTORS

Prematurity (< 36 weeks)

Lung Collapse

Multiple Pregnancy

Caesarean Section

Maternal Diabetes

Amniotic Fluid aspiration

Low Level surfactant

Hypoxia

Pulmonary Vasoconstriction

FIBRIN/HYALINE Membrane

Endothelial Damage

Alveolar Lining damage

IMMATURE/DAMAGED TYPE II PNEUMOCYTES

 Pathology

 The lungs: -

  1. Have fibrous obliteration of bronchioles
  2. Peribronchial fibrosis
  3. Overdistended alveolar

 Clinical Features

 If a baby is born before his lungs have matured, he will develop respiratory distress syndrome (RDS). A baby with RDS tries to cry and breathe at birth, but within minutes to hours he starts working hard to breathe because his lungs tend to collapse with each breath.

A baby with RDS:

  1. Breathes faster than 60 breaths a minute
  2. Makes a grunting sound when he breathes out
  3. Has respiratory distress (what are the features)  
  4. Has Cyanosis

 Diagnosis

 Certain laboratory tests are done to help determine the cause of the breathing problems. These tests include:

 1)      Blood culture

 All babies are treated for the possibility of infection with antibiotics. Before starting the antibiotics, a sample of the baby's blood is tested for infection. The test is called a blood culture. If the baby does not have an infection, the test will be negative and the antibiotics will be stopped in 3 days. 

 2)      Blood gas test: Blood gas tests show how much oxygen is in the bloodstream. This information helps your doctor know how much oxygen the baby needs. It also tells how hard the baby is working to breathe and whether he needs help to keep breathing.

 3)      Chest X-ray: X-rays for babies use very little radiation and do not cause the baby any problems later in life.

 Differential Diagnosis

  1. Pneumonia
  2. Extra fluid in the lungs

 Complications 

  1. Intracerebral bleed ( hypoxia related)
  2. PDA (failure to close as normal closure is stimulated by oxygenation)
  3. Necrotizing enterocolitis ( ischaemic/hypoxic damage of the gut)
  4. Bronchopulmonary dysplasia (high pressure ventilation and oxygen toxicity to alveolar lining cells)

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Topic 2: UPPER RESPIRATORY TRACT DISORDERS

EPISTAXIS

 Epistaxis is common as it is experienced by 60% of the population of which only 6% seek medical advice. The bleeding may be spontaneous or profuse and life threatening. Bleeding may originate from anywhere within the nose, but frequently from the Little’s area.

 Aetiology

 The peak incidence is in children, young adults and above the age of 55 years.

 Causes

 1.      Nasal

    1. Idiopathic (85%)        
    2. Trauma – nose pricking, fractures
    3. Inflammation – rhinitis, sinusitis
    4. Iatrogenic – nasal sprays, surgery
    5. Hereditary – Hereditary haemorrhagic telangiectasis
    6. Neoplasms – carcinoma, juvenile angiofibroma

 2.      Systemic

  1. Anticoagulants – warfarin, NSAIDS
  2. Hypertension
  3. Blood dyscrasias – leukaemia
  4. Hereditary coagulopathies – haemophilia

 ACUTE INFLAMMATIONS

 Infections of the nose, nasal sinuses, pharynx and larynx are common and usually self-limiting illnesses often because of viral infection, which on many occasions, is followed by bacterial superinfection.

 Viral Infections

 Viral infections have characteristic features of acute inflammation such as redness; oedema, nasal stuffiness, swelling of the nasal mucosa, duct obstruction and abundant clear nasal discharge (mucous secretion) without exudation of neutrophils.

 Aetiology

 1.      Rhinovirus

2.      Corona virus

3.      Myxovirus e.g. Influenza

4.      Paramyxovirus e.g. respiratory syncytial virus

 Bacterial Phase

 After the viral invasion, commensal bacteria present in the respiratory system e.g. Streptococcus mutans and Haemophilus influenza can superinfect the damaged tissue. This stage exhibits features of acute inflammation and exudation of neutrophils with a mucopurulent discharge.

 Pathogenesis

 Viruses adhere to the cell surface proteins e.g. the cilia and enter the host cells and replicate during which period the cells become damaged and readily invaded by commmensal bacteria                             

 1.  Common Cold (Acute Coryza)

 This is the commonest illustration of acute inflammations of the upper respiratory tract. It involves the nose and adjacent structures such as the nasal sinuses (maxillary, sphenoidal and frontal) where there occurs blocking of their drainage by the swollen mucosa resulting in sinusitis. Acute coryza is spread by droplet via sneezing.

  2.  Rhinitis

Rhinitis is inflammation of the mucous membranes of the nose.

3. Acute rhinitis 

The commonest causes of acute rhinitis are common cold (acute coryza) and hay fever.

4. Allergic Rhinitis “Hay Fever”

 Hay fever is an acute allergic or atopic rhinitis that occurs as a result of hypersensitivity (type I) to pollen, house dust, animal dandruffs and other antigens. Patients develop immediate symptoms of sneezing, itching and water rhinorrhoea.

5. Chronic Rhinitis

Chronic rhinitis follows an acute inflammatory episode that fails to resolve. As a result of acute inflammation there is inadequate draining of the nasal sinuses due to nasal obstruction, polyps or enlargement of the adenoids leading to chronic sinusitis and chronic nasopharyngitis.

 Acute Sinusitis

 Acute sinusitis occurs often as a complication of acute infection of the nose with the responsible organs such as Strep. pyogenes, Strep. pneumoniae and Staph. aureas.


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Topic 2: UPPER RESPIRATORY TRACT INFECTION (Cont')

Acute Nasopharyngitis

Acute nasopharyngitis usually accompany acute rhinitis or acute tonsillitis. The common organism implicated is Staphylococcus aureas.

The histopathology includes -

  1. Hyperaemia
  2. Oedema
  3. Hyperactive mucosal glands
  4. Increased mucosal secretions
  5. Neutrophil polymorphs – usually sparse in viral infections but increase with secondary bacterial infections
  6. Superficial destruction of ciliated epithelium
  7. Swollen/enlarged/distended mucosal glands

Nasal Polyps

Nasal polyps usually form on the middle turbinate bones and within the maxillary sinuses as a result of chronic recurrent inflammation of the nasal mucosa particularly of allergic aetiology that results in polypoid thickening of the mucosa.

Polyps are rounded or elongated masses that are usually bilateral with gelatinous consistency and smooth and shinny surface.

THE LARYNX AND TRACHEA

1.      Acute Laryngitis and Tracheaitis

Acute laryngitis and tracheaitis are common occurrences

Aetiology

1.      Viral

  1. Adeno virus
  2. Epstein Barr virus (EBV)

2.      Bacteria

  1. Strep. pneumoniae
  2. Strep. pyogenes
  3. Neisseria catarrhalis
  4. Heamophilus influenzae
  5. Corynebacterium diptheriae

 Acute laryngo-traheaitis complicates acute febrile states such as measles, influenza and typhoid and may spread to cause bronchitis resulting in laryngo-tracheo-bronchitis (LTB). In situations where there is secondary infection with Strep. pyogenes, Strep. pneumoniae and Staph. aureas leads to pseudomembranous inflammation.  Tonsillitis is common as a result of streptococcal infection while Heamophilus influenza type B usually causes acute epiglottitis, which is a childhood illness. 

 Chronic Laryngitis

 This is chronic inflammation of the larynx and trachea, which is frequently associated with excessive, smoking, repeated attacks of infection and atmospheric pollution.

 TB Laryngitis

 Tuberculous laryngitis is usually secondary to pulmonary tuberculosis when the tubercle bacilli are carried directly in the sputum to the larynx affecting the larynx and to a less extend to the trachea. It causes thickening, caseation and ulceration of the pharynx. The lesion is very painful and inflammatory swelling and oedema of the glottis may supervene.

Group Work – LTB

 1.      What are the causes?

2.      Definition and predisposing factors

3.      What is the pathophysiology and the pathology?

4.      What are the features?

5.      Diagnosis and differential diagnosis 

6.      What are the complications?

   

TUMOURS

 Benign tumours

  1. Polyps
  2. Squamous papilloma
  3. Lipomas
  4. Angiomas

 Malignant Tumours

 1.      Squamous cell carcinoma e.g. ca larynx.

 Laryngitis

 Laryngitis is inflammatory process/condition of the larynx due to various causes.

 Types

  1. Simple laryngitis/acute laryngitis
  2. Chronic laryngitis
  3. Diphtheric laryngitis 
  4. Tuberculous laryngitis
  5. Syphilitic laryngitis

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Topic 2: References

  1. Kishasha M (2016). Textbook of human pathology. 1st edition, Acrodile publishers, Nairobi, Kenya.
  2. Harsh M (2014). Textbook of Pathology. 1st edition. New Delhi: Jaypee Brothers, Medical Pub, India
  3. Ngton C, & Muir (2014). Textbook of Pathology. 15th edition, New Delhi. Jaypee Brothers, India

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Topic 3: LOWER RESPIRATORY TRACT CONDITIONS (RESPIRATORY FAILURE0

Respiratory Failure

INTRODUCTION

 Normal respiratory function maintains blood gases within physiological limits where the normal PaO2 is 10.7 kPa – 13.3 kPa (80 – 100 mmHg) and PaCO2 is 4.7kPa – 6.0 kPa (35 – 45 mmHg).

 Respiratory failure is defined as when PaO2 falls below 8 kPa (60 mmHg).It occurs when pulmonary gas exchange is sufficiently impaired to cause hypoxaemia with or without hypercarbia. It is a state when the arterial oxygen tension has fallen below 60 mmHg (8.0 kPa) as a result of lung diseases in a patient breathing at sea level. PaO2 < 8.0 kPa (60 mmHg) or PaCO2 > 7 kPa (55 mmHg).

 MECHANISMS OF ARTERIAL HYPOXAEMIA

  1. Low inspired partial pressure of O2 as a result of ambient air at high altitude and reduced oxygen tension in inspired air
  2. Mismatch of alveolar ventilation to perfusion
  3. Alveolar hypoventilation
  4. Increased shunt fraction of blood passing from the right heart to systemic arterial circulation in right to left cardiac shunts without being oxygenated
  5. Disease of the alveolar capillary membrane locking exchange of gases

Task: Using examples explain how the factors above cause respiratory failure. 

 CAUSES

 1.      Extrinsic Lung Disorders

a.    Respiratory centre depression

                             i.     Drug overdose (sedatives, narcotics)

                           ii.     Cerebral trauma or infarction

                         iii.     Bulbar poliomyelitis

                         iv.     Encephalitis

 b.    Neuromuscular disorders

                             i.Cervical cord injury

                           ii.Gullain-Barre Syndrome

                         iii.Myasthenia gravis

                         iv.Muscular dystrophy

 c.    Pleural and chest wall disorders  

                             i.     Chest injury (flail chest, rib fracture)

                           ii.     Pneumothorax

                         iii.     Pleural effusion

                         iv.     Kyphoscoliosis (abnormal lung)

                           v.     Obesity – Pickwickian syndrome

 2.      Intrinsic Lung Disorders 

a.    Diffuse obstructive disorders

                             i.     Emphysema and chronic bronchitis (COPD)

                           ii.     Asthma and status asthmaticus

                         iii.     Cystic fibrosis

 b.    Diffuse restrictive disorders

                             i.     Interstitial fibrosis e.g. silica and coal

                           ii.     Sarcoidosis

                         iii.     Scleroderma

                         iv.     Pulmonary oedema (cardiogenic, non-cardiogenic e.g. ARDS)

                           v.     Atelectasis

                         vi.     Consolidated pneumonia

 c.    Pulmonary vascular disorders

                             i.     Pulmonary emboli

                           ii.     Severe emphysema

 PREDISPOSING FACTORS

 Predisposing factors of respiratory failure in chronic lung disease include

  1.  Infection in the tracheobronchial tree, pneumonia, fever
  2. Change in tracheobronchial secretions (increased volume and viscosity)
  3. Bronchospasms
  4. Disturbance in ability to clear secretions
  5. Drugs – sedatives, narcotics, anaesthetics
  6. Oxygen therapy
  7. Trauma
  8. Cardiovascular disorders
  9. Pneumothorax

 CLASSIFICATION

 1.      Type I – “Acute hypoxaemic” respiratory failure

2.      Type II – “Ventilatory failure” respiratory failure

TYPE I RESPIRATORY FAILURE

This is a state of hypoxaemia without CO2 retention (blood carbon dioxide remains within the normal limits). Such patients are referred to as “pink puffers:

Causes

  1. Extensive lung disease
  2. Acute attacks of bronchial asthma
  3. Depression of respiratory tract
  4. Pulmonary oedema
  5. Pneumonia
  6. Lung collapse
  7. ARDS
  8. Pulmonary thromboembolism
  9. Extreme obesity
  10. Interstitial lung disease – Fibrosing alveolitis, Sarcoidosis, allergic alveolitis, asbestosis

Diagnosis

 1.      Arterial blood gases analysis – reduced PaCO2

2.      Respiratory function tests – reduced FEVR and FEV1

TYPE II RESPIRATORY FAILURE

Results from alveolar hypoventilation and is commonly from chronic bronchitis and emphysema. There is decreased PaO2 and increased PaCO2 (>  6.7 kPa/50 mmHg)

Causes

  1. Head injury
  2. Narcotic overdose
  3. Depression of respiratory centre
  4. Thoracic and chest wall deformities
  5. Chronic obstructive airway disease
  6. Upper airway obstruction
  7. Respiratory muscle weakness e.g. Gullein Barre Syndrome (GBS)
  8. Trauma – massive rib fractures

Mechanism

 Reduced alveolar ventilation results in reduced ventilator effort and there is inability of the alveolar to overcome increased resistance to ventilation.

 EFFECTS ON CVS

 Chronic respiratory failure has major effects in the cardiovascular system including pulmonary hypertension and polycythaemia.

 Pulmonary Hypertension

 Pulmonary vasoconstriction results in increased pulmonary artery pressure and increased work of the ventricles. The effects will be felt in pulmonary arteries resulting in intimal proliferation and occlusion of the lamina.

Polycythaemia

 Hypoxia stimulates release of erythropoietin by the kidney, which is the cause of increased viscosity of blood and the risk of thrombosis.

 FEATURES OF RESPIRATORY FAILURE

  1. Tachycardia
  2. Tachypnoea
  3. Sweating
  4. Use of accessory muscles of respiration
  5. Pulsus paradoxical
  6. Inability to speak
  7. Paradoxical respiration (abdominal and thoracic components move in opposite directions)
  8. Asynchronous respiration (discrepancy in the rate of movement of the abdominal and thoracic components)
  9. Respiratory alternans

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Topic 3: LUNG COLLAPSE /ATELECTASIS

Lung collapse comprises of atelectasis and acquired collapse. Atelectasis refers to incomplete expansion of the lungs (neonatal atelectasis) or the collapse of a previously inflated lung (acquired atelectasis) encountered in adults. ‘Atelectasis’ is a Greek word for imperfect expansion.

 Atelectasis has important clinical consequences of disturbing the respiratory function namely: -

    1. Obstruction of an airway results in resorption of air from the lung distal to the obstruction
    2. Compression of the lung as seen when fluid or air accumulates in the pleural cavity
    3. Scarring of the lung resulting in contraction of parenchyma and collapse
    4. Loss of normal surfactant (developmental or acquired) results in generalized failure of lung expansion (microatelectasis). 

 ATELECTASIS (Neonatal)

 Atelectasis is incomplete expansion of neonatal lung (failure of lungs to expand at birth).

 Aetiology

  1. Failure of the respiratory centre
  2. Prematurity – results in premature lungs due to lack of surfactant and immaturity of the respiratory centre
  3. Hyaline membrane disease
  4. Laryngeal dysfunction
  5. Obstruction of airway passages
  6. Idiopathic
  7. Cerebral damage – depresses respiration

 ACQUIRED LUNG COLLAPSE

 Can occur because of resorption atelectasis, compression atelectasis and contraction atelectasis. 

Lung collapse

  Resorption Atelectasis

 Resorption atelectasis occurs because of complete obstruction of an airway resulting in resorption of oxygen trapped in independent alveoli without impairing blood flow through the affected alveoli. Lung volume is reduced and hence the mediastinum shifts to towards the atelestatic lung. Excessive secretions e.g. mucous plugs or exudates with smaller bronchi may cause the obstruction.

 Resorption atelectasis is seen in bronchial asthma, chronic bronchitis, bronchiectasis, post-operative states and aspiration of foreign bodies.  Secretions then replace the air and oedema fluid, which become infected quite easily resulting suppuration and tissue destruction that results in irreversible pulmonary fibrosis.

Resorption

 Compression Atelectasis

 Compression atelectasis occurs when pleural cavity is partially or completely filled with fluid exudates; tumours blood or air e.g. pneumothorax and tension pneumothorax. Most commonly encountered in patients with cardiac failure who develop pleural effusion and patients with neoplastic effusions within pleural cavities. Pressure collapse results from compression of the lung tissue from without due to pressure on the visceral pleura fluid or air. The mediastinum shifts away from the affected lung

  Causes

  1. Pleural effusion
  2. Haemothorax
  3. Empyema
  4. Pneumothorax (spontaneous or tension) – accumulation of air in the pleural space following blunt or penetrating injury. Old patients with emphysema may develop spontaneous pneumothorax.
  5. Haemo-pneumothorax

 In pressure collapse there is no obstruction hence there is free drainage of secretions from the lungs and bronchi up the bronchial tree. The collapsed lung does not become seriously infected because of the free drainage status. Changes that take place in the lung tissue are as a result of haemodynamics and vascular alterations. Organization of the exudates on the pleural surface leads to pleural thickening, which prevents re-expansion of the lungs. Drainage of the plural cavity should be done in order to obtain re-expansion of the lung 

Compression atelectasis

 

Contraction Atelectasis

 

Contraction atelectasis occurs when local or generalized fibrotic changes in the lung or pleural cavity prevent full expansion of the lung.

Contraction atelectasis

CLINICAL TASK

 1.      What are the clinical features of lung collapse?

2.      What investigations will be important?

3.      What are the differentials?

 

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Topic 3: OBSTRUCTIVE PULMONARY DISEASE

The bronchi have ciliated ad mucous secreting cells that defend the airways and lungs against bacteria and foreign bodies. Some viruses are capable of causing damage to the cilia paving way for invasion by bacteria. Chronic irritation of the bronchi leads to hyperplasia and hypertrophy of the mucous secreting glands and goblet cells, which is a feature of chronic bronchitis in cigarette smokers.

 Obstructive pulmonary diseases affect the airways and are characterized by increased resistance to airway flow due to partial or complete obstruction at any level along the respiratory passages (trachea ® respiratory bronchioles). The main diffuse obstructive disorders are emphysema, chronic bronchitis, bronchiectasis and asthma.  Patients with these entities have limitations of maximal airflow rates during forced expiration at 1 second (reduced FEV1). 

 Disorders of Airflow Obstruction

Clinical Term

Anatomic site

Major Pathologic changes

Aetiology

Signs/symptoms

Chronic Bronchitis

Bronchus

Mucous gland hyperplasia and hypersecretion

Tobacco smoke and pollutants

Cough and sputum production

Bronchiectasis

Bronchus

Airway dilatation and scarring

Persistent or severe infections

Cough, purulent sputum and fever

Asthma

Bronchus

Smooth muscle hyperplasia, excess mucous and inflammation

 Immunologic or undefined causes

Episodic wheezing, cough and dyspnoea

Emphysema

Acinus

Airspace enlargement and wall destruction

Tobacco smoke

Dyspnoea

 

Emphysema and chronic bronchitis are grouped together as chronic obstructive pulmonary diseases (C.O.P.D) or chronic obstructive airway diseases (C.O.A.D). COPD refers to patients who have largely irreversible airways obstruction. Asthma may be a component of COPD in some patients. The key aetiological factors in COPD are smoking (major risk), environmental pollutants (e.g. occupation – mines, dust) and a1-antitrypsin deficiency.   

 Bronchial Obstruction

 Bronchial obstruction occurs in various degrees from partial obstruction to complete obstruction affecting small and large bronchi. The obstruction, which may be sudden or gradual, results in accumulation of secretions with oedema formation leading to some degree of dilatation of the bronchi. Secondary bacterial infection ensues producing suppurative bronchitis and by extension suppurative bronchopneumonia.

 CAUSES

  1. Tumours - Bronchial carcinoma and Bronchial adenoma
  2. Enlarged tracheobronchial lymph nodes – malignancy, tuberculous
  3. Inhaled foreign body (FB)
  4. Bronchial casts or plugs consisting of inspissated mucous or blood clot
  5. Collections of mucous or mucopus retained due to ineffective expectoration
  6. Congenital bronchial atresia
  7. Fibrous bronchial stricture (post TB)
  8. Aortic aneurysm
  9. Giant left atrium
  10. Pericardial effusion

 Bronchial Obstruction

Bronchial obstruction

 EFFECTS

1.      Lung collapse

 Complete obstruction of the bronchioles leads to absorption of the air in the alveoli with the alveolar spaces collapsing. The lung tissues collapse and become solid producing a dull note on percussion. The breath sounds either are reduced or absent; trachea is displaced and the diaphragm is elevated  

 2.      Emphysema (obstructive) - Results in a resonant note on percussion, diminished breath sounds and a displaced mediastinum

3.      Secondary infection/suppuration

4.      Impaired pulmonary function – dyspnoea and hypoxaemia

5.      Features related to obstruction

TASK

O  Explain the pathophysiology of the effects above.

O  What investigations will be relevant in such patients
 
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Topic 3: EMPHYSEMA

Emphysema is abnormal permanent dilatation/enlargement of airspaces distal to the terminal bronchiole accompanied by destruction of the bronchiole walls without fibrosis. It is a constituent of COPD/COAD.

Emphysema

AETIOLOGY

 The main factors are -

  1. Smoking – major risk factor that is dose related
  2. a1-antitrypsin deficiency – a protease inhibitor that prevents lung damage especially in smokers
  3. Occupation – dusty environment e.g. coal mines

 PATHOGENESIS

 It Is due to imbalance between protease and anti-protease activities in the lung resulting in destruction of the alveolar walls (This is referred to as the Anti-protease hypothesis

Ø  a-1-antitrypsin (a-1-protease inhibitor) is a glycoprotein constituent of globulin in plasma is synthesised in the liver and is usually present in serum and tissue fluids. Protease inhibits protelytic enzymes, which degrade elastin or neutrophil derived elastase. Increased neutrophil infiltration of the lung causes excessive production of elastase

Ø  Deficiency of a-1-antitrypsin occurs in homozygous states however in smoking accelerates the damage in heterozygous situations  

ü Smoking

Ø  Reduces anti-elastase and increases elastolytic protease in the lungs due to oxidants in cigarette smoke which inhibit a-1-antitrypsin

Ø  Smokers have increased phagocytes and neutrophils in the lungs

ü After the damage the pressure inspired air expands the damaged portion into an emphysematous space 

ü With continued enlargement more pressure is required to cause further dilatation resulting in increased dilatation and damage

ü Coughing in chronic bronchitis aggravates the situation       

 Pathogenesis of Emphysema

Smoking

Elactase normally inactivated by protease inhibitors (e.g. a-1-antitrypsin)

Neutrophils and macrophages release elastase

Elastases destroy alveolar wall

 Emphysema

. a-1-antitrypsin deficiency leads to failure of elastase inactivation

PATHOLOGY

Macroscopy

  1. Voluminous pale lungs
  2. Dilatation of air spaces

Microscopy

  1. Dilatation of air spaces
  2. Destruction of septal wall resulting in thin walls
  3. Compressed capillaries
  4. Rupture of walls producing honeycombs

 CLASSIFICATION

 Classification is based on anatomical distribution within the lobule.

  1. Centrilobular/centriacinar
  2. Panaacinar/panlobular
  3. Paraseptal/distal acinar
  4. Irregular

 Centrilobular/Centriacinar

  1. Predominant in male smokers and chronic bronchitis
  2. Central or proximal parts of the acinar are involved
  3. Involves enlargement of terminal airspaces and the respiratory bronchioles because of destruction and enlargement of the central or proximal parts of the respiratory unit (the acinar).
  4. Distal acinar are spared
  5. Associated with cigarette smoking, chronic bronchitis and inflammation of distal airways

 Panacinar (Panlobular) Emphysema

  1. Affects all acinar
  2. Acinar uniformly enlarged from the level of the respiratory bronvhioles to the terminal blind alveoli
  3. Associated with  a1-antitrypsin deficiency

 Distal Cinar (Paraseptal) Emphysema

  1. Affects distal portion of the acinus
  2. Proximal portions of the acinus are spared
  3. Usually due to infections accompanied by inflammatory changes and fibrosis

Irregular Emphysema

  1. Acinar irregularly affected
  2. Mainly associated with scarring
  3. Most common form of emphysema

Types of Emphysema.

Types of Emphysema

 CLINICAL FEATURES

  1. Cough, expectoration  
  2. Wheezing
  3. Slowly increasing severe exertional dyspnoea
  4. Respiratory distress
  5. Chest – barrel shaped
  6. Hyper-resonant percussion note
  7. Hyperventilation
  8. Tachycardia
  9. Patients are “pink puffers” – they remain well oxygenated and have tachycardia; do not tolerate, hypoxia 
  10. Weight loss

 COMPLICATIONS

TASK

 Ü  Compare and contrast emphysema and chronic bronchitis.

Ü  State the important investigations
 

  1. Cor pulomonale
  2. Congestive Cardiac failure
  3. Pulmonary hypertension 

CAUSES OF DEATH

  1. Respiratory acidosis
  2. Coma
  3. Right sided heart failure
  4. Massive lung collapse due to pneumothorax


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Topic 3: BRONCHIECTASIS AND BRONCHITIS

Bronchiectasis is localized or generalized permanent abnormal dilatation of the bronchi or bronchioles (more than 2 mm in diameter) caused by destruction of the muscle and elastic tissue, resulting from or associated with chronic necrotizing infections.  It usually results from the weakening of the bronchial wall a sequel of destruction of elastic and muscular components of the walls following necrotizing infection of the bronchi and bronchioles. 

 AETIOLOGY

 There are three main categories: -

  1.  Pulmonary infection
  2. Bronchial obstruction
  3. Complication of certain conditions

 Pulmonary Infection

 Chronic necrotizing inflammation of the bronchial walls causes destruction of the elastic and muscle tissues resulting in damage of the walls leading to dilatation of the bronchi. The dilatation allows accumulation and stagnation of the secretions that easily become secondarily infected causing further damage of the bronchial wall. Microorganisms associated with this phenomenon are bacterial infection with Mycobacterium tuberculosis, Heamophilus influenzae, Staphylococcus and fibrosing, suppurative pneumonias and corrosive chemicals. Infection may be primary infection of secondary to local obstruction and impaired systemic defence systems.

 Inflammation results in loss of aerated lung impairing the inspiratory expansion force of the chest, mechanical weakening of the bronchial walls and contraction of the fibrous bands connecting bronchial wall with the fibrosed and adherent pleura (interferes with intrapleural pressure hence lung dilatation).

 Obstruction

 Obstruction of the bronchi leads to accumulation and stagnation of secretions, which are later, infected resulting in an inflammatory reaction that leads to destruction and weakening of the bronchial walls facilitating dilatation of the bronchi. The obstruction could be due to foreign bodies, bronchogenic carcinoma and extrinsic factors (tumour, hilar lymph node, inflammatory oedema, post inflammatory scaring in tuberculosis). May lead to atelectasis.

 Associated Conditions

 Bronchiectasis may occur as a sequel of other disease processes or hereditary and congenital factors

 1.      Congenital and hereditary conditions

    1. Cystic fibrosis
    2. Intralobular sequestration of the lung
    3. Immunodeficiency states
    4. Kartagener’s syndrome ((Bronchiectasis, sinusitis, displacement of viscera (heart) – immobility of the cilia
    5. Congenital bronchiectasis
    6.  Atelectasis

 2.      Post infection conditions

a.       Necrotising pneumonia caused by bacteria (Myocobacterium tuberculosis, Staphylococcus aureus, Haemophilus influenza and Pseudomonas), viral (HIV, adenoviruses and influenzae), fungal (Aspergillus)

 3.      Bronchial obstruction

  1. Tumours
  2. Foreign bodies
  3. Mucous impaction

 4.      Others

a.       Bronchiolitis and bronchopneumonia in childhood

b.      Rheumatoid arthritis

c.       S.L.E

d.      Inflammatory bowel syndrome

e.       Post-transplant

PATHOGENESIS

The major factors in the pathogenesis of bronchiectasis are obstruction and infection.

Obstruction

Hereditary, congenital and mechanical obstruction of the bronchi predisposes to bronchopulmonary infection and sputum retention a common occurrence in necrotizing pneumonia. Obstruction reduces mural clearing mechanisms resulting in pooling of secretions distal to the point of obstruction and increases susceptibility to infections.

Necrotizing inflammation results in destruction of the bronchi and bronchioles leading to formation of multiple large spaces or cavities. This destruction tends to include the surrounding lung tissue, which heals by fibrosis with resultant obliteration and destruction of smaller bronchi and bronchioles. 

The cavities formed accommodate a lot of secretion within the bronchi. These secretions become infected becoming purulent. Without treatment of the infection the fluid trapped within the cavities become persistently infected by putrefying microorganisms resulting in formation of purulent fluid that becomes decomposed producing foul smelling breath and sputum. The organisms spread from this focus to the alveoli by air passages or direct spread through the vein forming a septic embolus that forms secondary abscesses (especially in the brain).  

Destruction of the bronchi involves ulceration of the bronchial walls. The respiratory passage may wholly or partly be lined by respiratory simple columnar epithelium but later become squamous metaplasia. Haemoptysis which may be little or massive occur as bleeding from thin walled vessels in the dilated bronchi/bronchioles.

Chronic bronchiectasis leads to haemodynamics changes due to alveolar hypoxia and fibrous obliteration of the pulmonary arteries, which results in enlargement, and development of bronchopulmonary vascular anastomoses.

Pathogenesis - Obstruction

Infections

Repeated infections results in increased damage to the airway walls with destruction of the supportinh smooth muscle and elastic tisiues and eventually fibrosis with further dilatation of the bronchi. the infection also causes necrosis of the walls leading to healing with fibrosis hence dilatation of the bronchi. small bronchi progressively become obliterated due to fibrosis (bronchitis obliterans)

PATHOLOGY

What is the relationship between Bronchiectasis and cystic fibrosis

 

Macroscopy

1.      Dilated bronchi with thickened walls

2.      Lumen filled with mucous or muco-pus

3.      Firbrotic surrounding lung

4.      Dilatation

a.       Cylindrical – most common tube-like bronchial dilatation

b.      Fusiform – spindle-shaped dilatation

c.       Saccular – rounded sac-like dilatation

d.      Varicose – irregular bronchial enlargements

Microscopic

1.      Epithelium - Normal , Ulcerated

q  Squamous epithelium

2.      Bronchial wall

a.       Infiltrated by acute and chronic inflammatory cells

b.      Destruction of muscle and elastic tissues

3.      Lung fibrosis

4.      Adherent pleura

CLINICAL FEATURES

1.      Severe , persistent/chronic cough

2.      Sputum – haemoptysis, foul smelling, purulent

3.      Recurrent pneumonia

4.      Fever, weight loss, anaemia, weakness

5.      Sinusitis

6.      Digital clubbing

7.      Metastatic abscess

8.      Cyanosis

DIAGNOSIS

1.      Bronchophony

2.      Bronchoscopy

3.      Sputum – colour, volume, cellular component, bacterial infection, Gram stain, culture, white blood cells, bacteriological examination

4.      Blood count

5.      ECG

6.      Urinalysis

7.      Oxygen tension

8.      Lung function tests 

EFFECTS/COMPLICATIONS

1.      Suppuration/empyema

1.      Septic emboli (Brain abscess)

2.      Pyaemia

a.       Brain abscess (metastatic)

b.      Meningitis – from involvement of the pulmonary vein

3.      Finger clubbing (Hypertrophic pulmonary osteodystrophy)

4.      Pulmonary hypertension

5.      Cor pulmonalae

6.      Amyloidosis

7.      COPD

8.      Recurrent pneumonia


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Topic 3: BRONCHITIS

Acute Bronchitis

This is inflammation of the large and medium bronchi.

Aetiology

1.      Viral 

  1. Respiratory syncytial virus
  2. Rhinovirus
  3. Echovirus
  4. Parainfluenza types 1, 2 3
  5. Influenza
  6. Herpes viruses
  7. Coxsackie viruses
  8. Corona viruses
  9. Adenoviruses
  10. Measles

2.      Mycoplasma - Candida albicans, Candida tropicalis, Histoplasma capsulatum and Cryptococcus neoferans

 3.      Bacteria (secondary infection) - Strep pneumonia, H. Influeanzae, Strep pyogenes (common in infants, ), Staph aureus (common in infants) and Salmonella typhi

 Pathogenesis

  1. Invasion by virus leads to inflammatory reaction by the bronchial epithelium
  2. There is activation of the mucous and serous glands leading to production of mucous secretions that cause crackles on auscultation.
  3. The ciliated epithelium aids in pushing the exudate upwards preventing spread into the bronchioles.
  4. Spread of the inflammatory reaction to involve the bronchioles in debilitated subjects results in bronchiolitis and bronchopneumonia which is fatal.
  5. Because of inflammatory oedema there is reduction in lumen size resulting in wheezing and rhonchi.   

 Pathology

 Macroscopy

  1. Congested
  2. Swollen/oedematous
  3. Hyperaemia
  4. Tenacious mucous exudate
  5. Sputum – yellow/green

Microscopy

  1. Congested mucosa
  2. Infiltration by neutrophils

Clinical Features

  1. Cough – initially unproductive but later yellow/green sputum.
  2. Wheezes/rhonchi
  3. Crepitations
  4. Shortness of breath
  5. Fever
  6. Neutrophilia

Bronchiolitis is inflammation of small, intralobular bronchi and bronchioles seen in children, old people and debilitated states. It is fatal as organisms spread to adjacent acini resulting in bronchopneumonia.

Catarrhal bronchitis is characterized by excessive secretion of mucous and increased inflammatory exudate. The mucoid sputum becomes mucopurulet after invasion by bacteria such as Strep. pneumoiae, H. influezae, Strep. pyogenes ad Staph. aureas.  In severe cases superficial layers are sloughed off resulting in ulcer formation (ulcerative bronchitis).

Chronic Bronchitis

Chronic bronchitis is defined clinically as persistent cough with sputum production on most days for at least 3 months in at least 2 consecutive years. It is not primarily an inflammatory condition but consists of metaplastic changes as a result of chronic irritation of the bronchial epithelium.

Aetiology

1.      Smoking

Prolonged cigarette smoking impairs cilia movement, causes hyperplasia and hypertrophy of mucous secreting glands, inhibits function of alveolar macrophages and stimulates the vagus nerve causing bronchoconstriction.

2.      Atmospheric pollution

Sulphur dioxide, nitrous oxide, toxic fumes and particulate dust particles.

3.      Occupational hazards - Cotton mills, Plastic factories 

4.      Infection

Bacterial, viral and myocoplasmal infections occur as a result of bronchitis

Predispose to acute exacerbations of chronic bronchitis 

5.      Familial/genetic factors

Poorly understood

Evolution of Chronic Bronchitis

Bronchiolar and Bronchial injury

Bronchospasms

Infections

Hypersecretion of mucous

Reversible obstruction in bronchioles and small bronchi

Chronic Bronchitis

Continued and repeated infections

Continued and repeated injury (e.g. smoking)

Pathogenesis

Chronic irritation of the bronchial epithelial cells results in pronounced hypertrophy and hyperplasia of the mucous glands leading to excessive secretion of mucous secretions.

There is increased number and proportion of goblet cells at the expense of ciliated cells, which are reduced

Excessive mucous production and destruction of cilia leads to accumulation of the secretions and exudate in the bronchi and bronchioles causing obstruction. This extends to involve the bronchioles hence bronchiolitis ensues.

Destruction of the epithelial causes some areas of ulceration, which heal by fibrosis causing narrowing of the bronchial lumen.

Invasion of the secretions by bacteria mainly H. influenzae and Strep. pneumoniae results in secondary infection leading to pus formation.  

Destruction of the epithelia occurs resulting in metaplasia where the squamous epithelium is replaced by columnar epithelium.    

Pathophysiology

Mucous hypersecretion is a physiological response to inhaled irritants

Increased secretion impairs normal clearance

Impaired cilia function and increased accumulation of mucous secretions leads to accumulation of the mucous.

There is increased susceptibility to acute respiratory infections with bacterial infections leading to suppuration.   

Pathology

Macroscopy

  1. Hyperaemia and oedema of mucous membrane
  2. Mucous secretions
  3. Increased size of mucous glands
  4. Plugging of bronchi and bronchioles
  5. Fibrosis
  6. Inflammatory changes

Microscopy

  1. Venous congestion
  2. Metaplasia
  3. Hypertrophy
  4. Dysplasia
  5. Inflammatory cells
  6. Increased thickness of the mucosal gland layer  (at post mortem, Reid index which is the ratio of glandular layer to the whole thickness is significant if the value is more than 1:2.)

 Differential Diagnosis

  1. Bronchial asthma
  2. Emphysema
  3. COPD
  4. Bronchiectasis
  5. Chronic pulmonary infections
  6. Chronic sinusitis with post-nasal drip 

 Complications

  1. Respiratory failure
  2. Emphysema


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Topic 3: ASTHMA

Bronchial asthma is a chronic relapsing inflammatory disorder characterized by increased responsiveness of the tracheobronchial tree to various stimuli resulting in widespread paroxysmal contraction of bronchial airways due to muscular spasms and plugging by increased thick mucous secretions from the mucosal glands.

 The changes that occur result in a state whereby the respiratory tree is drawn longer with a reduced diameter forming a physiological valve mechanism that leads to easy or normal inspiration and difficult and prolonged expiration. The short inspiration and long expiration produces the characteristic wheeze/rhonchi in bronchial asthma.  

 The wide spread narrowing of the respiratory tree may be relieved spontaneously or by therapy but if relieve is not attained a severe and unremitting state of the disease called status asthmaticus which is usually fatal ensues.

 Asthmatic attacks cause shortness of breath and wheezing respirations as a result of restricted movement of air through tightly constricted air passages. The bronchial spasms exert great effect on expiration than inspiration because the calibre of bronchioles varies with the phase of respiration.

 AETIOLOGY

 The aetiology is unclear but associations exist with genetic make up, atopy or allergy and increased responsiveness of the airways.

 CLASSIFICATION

  1. Extrinsic (atopic, allergic) asthma
  2. Intrinsic (cryptogenic, non-atopic, idiosyncratic) asthma.
  3. Exercise induced asthma
  4. Drug induced
  5. Occupational asthma
  6. Asthma associated with COPD

 Extrinsic (Atopic, Allergic) Asthma

 This is the commonest type of asthma that has a definite cause associated with the disease as it runs in families and individuals with history of allergy. The individuals may have a history of diseases such as rhinitis, urticaria and infantile eczema. Atopic or extrinsic asthma begins in childhood and early adult life.

 Subjects with extrinsic asthma have increased levels of IgE representing type I hypersensitivity reaction mechanisms and they do show characteristic wealing skin reactions to common allergens in the environment.

 Pathogenesis

 Exposure of pre-sensitized IgE coated mast cells to allergens (antigens) results in release of chemical mediators in a reaction that first takes place on the mucosal surface and results in the opening of the intercellular tight junctions thereby enhancing penetration of the mast cells by antigens to reach the numerous submuocal mast cells. This reaction occurs within minutes (acute or immediate response)

 Direct stimulation of the subepithelial vagal (parasympathetic) receptors provokes bronchoconstriction through both central and local reflexes.

 This is an acute or immediate response, which consists of bronchoconstriction, oedema, mucous secretion and hypotension (in severe cases).

 Mast cells release cyokines, which result in influx of leucocytes (neutrophils, monocytes, lymphocytes, basophils and oesinophils) which mediate the late phase reaction together with recruited chemotaxic factors.

 Other sources of mediators of the late phase reaction include the vascular endothelium and airway epithelial cells(produce cytokines in response to infection, drugs and gases.

Intrinsic Asthma (Non-atopic)

Intrinsic asthma develops in adult life staring during the middle age and is commonly associated with chronic bronchitis. There is a negative family history of the disease as well as personal history of allergy as these individuals fail to reveal a responsive allergen. However, there may be a history of respiratory symptoms compatible with childhood asthma.  Individuals with intrinsic asthma tend to develop drug hypersensitivity especially with aspirin and penicillin.

Drug Induced

Drugs such as aspirin trigger asthma by inhibiting COX pathway of arachidonic acid metabolism without affecting the lipoxygenase route thus resulting in increased production of bronchoconstritive leukotrienes.

Occupational Asthma

Occupational asthma is stimulated by fumes (epoxy resin, plastics), organic and chemical dusts (wood, cotton, platinum), gases (toluene), chemicals (formaldehyde and penicillin products).

PATHOGENESIS

The pathogenesis of bronchial asthma pivots around: - Airway hypersensitivity, Inflammation and Airway obstruction

Airway Hypersensitivity

There is increased responsiveness of the respiratory airways of the lung to allergens in the environment whose inhalation triggers an immediate acute response initiated by IgE sensitised mast cells in the mucosal surface of the respiratory tree. The mast cells degranulate releasing mediators of inflammation such as histamine, leukotrienes, prostaglandins and platelet aggregating factor (PAF) and chemostatic factors for oesinophils and neutrophils.

The respiratory tree is hypersensitive to normal allergens, which can trigger off reactions. These allergens include inhaled and non-inhaled ones. The inhaled allergens include - aeroallergens (house dust mites, pollens, animal dander and fungal spores) air pollution, extreme cold. The non-inhaled are exercise and ingested substances.

Inflammation

Following the hypersensitivity reaction and release of mediators of inflammation, there ensues an inflammatory reaction that results in oedema formation, bronchoconstriction and hypersecretion of mucous and accumulation of oesinophils and neutrophils. There is   infiltration of the airways with inflammatory cells, Thelper lymphocytes, oesinophils and mast cells, which is a common feature in asthma.

Airway Obstruction

The pathologic basis of airway obstruction is: -

  1. Constriction of the airway’s smooth muscles due to release of bioactive mediators and neurotransmitters.
  2. Thickening of the airway epithelium due to oedema formation
  3. Presence of liquids and mucous secretions within the confines of the bronchial lumen

Mast Cells

The number of mast cells is increased in the respiratory epithelium and surface secretions. Mast cells generate and release powerful smooth muscle and vasoactive mediators such as histamine, prostaglandin D2 (PD2) and leukotrienes C4 (LTC4) that cause the immediate asthmatic reaction. Note that b2 adrenoreceptor e.g. salbutamol inhibit release of mediators by the mast cells.

The Epithelium

Following the inflammatory reaction, epithelial cells shed during exacerbations of asthma results in desquamations, which increase permeability of the airway to inhaled allergens and exposure of nerve fibre endings. These desquamated materials from the columnar epithelium can be identified in the sputum as twisted strips called Curschmann’s spirals.

The inflamed epithelium produces mediators such as cytokines, granulocytes macrophage colony stimulating factor (GM-CSF) that prolong the life of tissue oesinophils, TNF and interlukins that capture the inflammatory cells within the epithelium.

Nerves

Exposure of the nerve endings especially C-fibre afferent nerves leads to release of neurotransmitters such as substance P, neurokinin (NK) A and calcitonin gene-related peptide (CGRP) which are tachykinins that increase the inflammatory response. This usually contributes to bronchoconstriction, microvasculature leakage and mucous secretion.  Vasoactive intestinal peptide (VIP) and nitric oxide are potent neurotransmitters that are rapidly degraded in inflammation resulting in bronchoconstriction.

The a and badrenergic systems of the autonomic nervous system are activated resulting in increased release of mediators from the mast cells but the cholinergic system which is extensive in the smooth muscles of the respiratory passages remains normal is asthma.

 INFLAMMATORY CELLS

 Macrophages and Lymphocytes

 Macrophages and lymphocytes are abundant in the mucous membranes of the airways and alveoli. The macrophages usually take up and present allergens to the lymphocytes and release prostaglandins, PAF and leukotrienes. TH lymphocyte cells are activated to release cytokines, which aid in migration and activation of mast cells. Production of IL-4 switches antibody production by B-lymphocytes to IgE. Macrophages and lymphocytes are influenced by corticosteroids and not by b-adrenergic agonists. 

Oesinophils

Oesinophils are abundant in bronchial secretions and when activated they release mediators such as PAF and LTC4, major basic protein (MBP) and eosinophil cationic protein (ECP) which are toxic to epithelial cells. The number and activity of eosinophils is rapidly decreased by corticosteroids. Oedema, vascular congestion and infiltration by oesinophils produce the Charcot Leyden crystals.

Vascular Epithelium

The vascular endothelium exhibits congestion, leakage, increased permeability and contraction.  b2 agonists and theophylline can prevent the contraction.

PATHOPHYSIOLOGIC CHANGES IN ASTHMA

  1. Airway obstruction due to smooth muscle constriction, thickening of the airway epithelium or free liquid within the airways.
  2. Increased resistance to airflow due to increased resistance within the airways
  3. Reduced flow rate throughout the vital capacity  

Precipitants

  1. Occupational sensitises
  2. Non-specific - cold air, exercise, diet, atmospheric pollution/irritants, dust, vapours, fumes, emotion, drugs e.g. NSAIDS
  3. Allergens
  4.  Infections

 Pathology

 Macroscopy (at autopsy)

  1. Overinflatted lungs that do not deflate when the thorax is opened
  2. Widespread plugging of airways with thick mucous 

 Microscopy

  1. Desquamation of the epithelium
  2. Hypertrophy of smooth muscle
  3. Thickening of the basement membrane
  4. Infiltration by oesinophils and inflammatory cells
  5. Hyperplasia of mucosal glands
  6. Goblet cell metaplasia
  7. Curschmann’s spirals – mucosal plugs containing normal or desquamated epithelium forming twisted strips.
  8. Charcot Leyden crystals – sputum containing numerous oesinophils and diamond shaped crystals derived from eosinophils.

CLINICAL FEATURES

Clinical features of asthma vary with age, severity, duration of disease, amount and nature of treatment and presence of complications.

  1. Main Features include – cough, headache, difficulty in breathing, hyperventilation, wheezing and chest pain/tightness
  2. Severe asthma
    1. Inability to complete a sentence in one breath
    2. Respiratory rate > 25 breaths per minute
    3. Tachycardia > 110 (pulsus paradoxicus)
    4. PEFR < 50% of predicted normal best
  3. Life threatening asthma
    1. Silent chest, cyanosis or feeble respiratory effort
    2. Exhaustion, confusion or coma
    3. Bradycardia, hypotension
    4. PEFR < 30%

 DIFFERENTIAL DIAGNOSIS

 Common

  1. Acute bronchiolitis (infections, chemical)
  2. Aspiration (foreign body)
  3. Bronchial stenosis
  4. Cardiac failure
  5. Chronic bronchitis
  6. Cystic fibrosis
  7. Eosinophilic pneumonia

 Uncommon

  1. Airway obstruction due to masses
    1. External compression (thoracic, superior vena cava syndrome, substernal thyroid)
    2. Intrinsic airway – pulmonary lung cancer and metastatic breast cancer
  2. Pulmonary emboli

 INVESTIGATIONS

 1. Lung Function tests – diagnosis of asthma is based on demonstration of a > 15% improvement I FEV1 or PEFR following inhalation of a bronchodilator.

  1. Peak flow charts – take PEFR on walking, middle of the day and before bed. It shows reduced PEFR, MMEFR
  2. Reduced FEV1

Note: FEV1 is reduced in obstructive disease > in restrictive disease

During an asthmatic attack FEV1 is greatly reduced while FVC is increased hence the ration is markedly reduced  

2.      Exercise tolerance

3.      Analysis of arterial gases

Check for the partial pressures of oxygen and carbon dioxide

The normal partial pressure for oxygen PaO2 is over 12 kPa (90 mmHg) and PaCO2 is less than 6.0 kPa (45 mmHg). This is reversed I asthma due to carbon dioxide retention resulting from the physiological valve.

4.    Haemogram - increased haemoglobin, normal WBC (only increase in the presence of an infection), eosinophils > 0.4 x 109/L

 5.      Sputum Examination

  1. Charcot Leyden spirals
  2. Curschmann’s crystals
  3. White blood cells

6.      Bronchial provocation test (is not done if the FEV1 is < 1.5 litres)

7.      Chest X-ray - shows hyperinflation, depressed diaphragm and excludes pneumothorax (a complication)

8.      Skin test

9.      Allergen provocation test

 COMPLICATIONS

  1. Pneumothorax
  2. Pneumomediastinum
  3. Respiratory failure
  4. Heart failure/CCF
  5. Cor Pulmonale
  6. COPD

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Topic 3: RESTRICTIVE PULMONARY DISEASES

Chronic restrictive pulmonary diseases form a large group of diffuse lung diseases.    Restrictive pulmonary diseases is a group of lung diseases that cause reduced compliance of the lungs resulting in difficult to expand with respiration usually because of abnormalities of alveolar walls which are rigid due to oedema or fibrosis (common),

 Acute restrictive lung disease is characterized by oedema and exudation whereas chronic restrictive lung diseases present with inflammation and fibrosis. Chronic restrictive lung disease is characterized by reduced expansion of the lung parenchyma with reduced total lung capacity.

 CLASSIFICATION

 There are three types: -

 1.      Restriction due to chest wall disorders such as: -

  1. Kyphosis
  2. Poliomyelitis
  3. Severe obesity

2.      Pleural diseases (see  later in the unit)

3.      Restriction due to interstitial and infiltrative diseases characterized by non-infectious involvement of interstitial connective tissue of the lung parenchyma. Infiltration denotes radiological appearance of the lungs in chest radiographs.   They include: -

a.       Fibrosing diseases

                                i.      Idiopathic

                              ii.      Interstitial pneumonia

                            iii.      Crytogenic pneumonia

                            iv.      Pneumoconiosis

                              v.      Drug reactions

                            vi.      Radiation pneumonitis

b.      Granulomatous diseases

                                i.      Sarcoidosis

                              ii.      Hypersensitivity pneumonitis

c.       Collagen vascular

d.      Oesinophilic

e.       Smoking related

f.        Others – pulmonary alveolar proteinosis

PATHOGENESIS

Restrictive lung diseases are characterized by damage to the alveolar walls resulting in haemorrhage and high protein exudation into the alveolar producing the hyaline membrane disease; oedema and inflammation of interstitium and fibrosis in the interstitial.

Pathogenesis

CLINICAL FEATURES

  1. Dyspnoea
  2. Tachycardia
  3. End-inspiratory crackles
  4. Cyanosis without wheezing or evidence of airway obstruction
  5. CXR shows diffuse infiltration by small nodules, irregular lines and grand glass shadows
  6. Secondary pulmonary hypertension
  7. Right heart failure
  8. Cor pulmonale
  9. Reduced CO diffusing capacity
  10. Reduced lung volume
  11. Reduced lung compliance

PNEUMOCONIOSIS

Introduction

Pneumoconiosis is a lung disease caused by inhalation of dust (dust diseases/occupational lung disease). The type of disease produced varies according to the nature of the dust causing the problem.

The extent of damage caused by inhaled gases is determined by: -

1.      Size and shape of the particles

2.      Solubility and physiochemical composition

3.      Amount of dust retained in the lungs

4.      Additional effects of other irritants such as tobacco.

5.      Host factors – efficiency in clearing mechanisms and immune status

 Tissue response will include –

 1.      Fibrous nodules e.g. coal-workers pneumonitis and silicosis

2.      Interstitial fibrosis e.g. asbestosis

3.      Hypersensitivity reactions – e.g. in berylliosis

FIBROSING LUNG DISEASE (INTERSTITIAL LUNG DISEASE)

Introduction

Fibrosing lung disease is characterized by chronic inflammation in the walls of the alveoli resulting in progressive diffuse fibrosis in the lung parenchyma. It presents with dyspnoea and dry cough

Cause of Chronic Interstitial Lung Disease

1)      Idiopathic interstitial pneumonitis (interstitial pneumonia)

2)      Connective tissue disease e.g. rheumatoid disease

3)      Drug induced damage e.g. cytotoxics

4)      Atypical pneumonia (Chlamydia, Mycoplasma)

5)      Pneumonia

6)      Extrinsic allergic alveolitis

7)      Sarcoidosis

8)      Radiation damage 

SILICOSIS

Introduction

Silicosis is caused by prolonged exposure to silicon dioxide (silica/quartz). This is common in slate mining, metal foundries, stone masonary, tunnelling, granite quarrying and coal mining.

In silicosis, the lung lesions slowly progress over many years. It damages lung macrophages and if the exposure is chronic thus leads to death of macrophages. There is release of cytokines, which enhance fibrosis. A silicotic lung is susceptible to tuberculosis

Clinical Features

Dyspnoea

Complications

 1.      Obstructive pulmonary disease

2.      pulmonary tuberculosis

3.      rheumatoid arthritis (Caplan’s syndrome)

4.      Cor pulmonale


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Topic 3: RESTRICTIVE PULMONARY DISEASES (CONT')

ASBESTOSIS

Introduction

Asbestosis causes lung and pleural diseases. It produces pleural plaques, pleural effusions, visceral pleural fibrosis, asbestosis (chronic progressive fibrosis of the lung), malignant mesothelioma (a highly malignant lung tumour) and cancer of the lung (bronchogenic carcinoma).

Clinical Features

  1. Insidious onset
  2. Dyspnoea
  3. Cough – dry or productive
  4. Pulmonary hypertension
  5. Cor pulmonale
  6. Various forms of cancer

ADULT ACUTE RESPIRATORY DISTRESS SYNDROME

Introduction

Adult Acute Respiratory Distress Syndrome is a manifestation of diffuse alveolar damage with widespread systemic metabolic derangements. The diagnosis depends on presence of precipitant ARDS, refractory hypoxaemia (PaO2 < 8.0 kPa in > 40% O2), radiological evidence of evolving pulmonary shadowing and clinical signs of lungs being abnormally rigid with low total compliance.

Causes

  1. Major trauma especially associated with increased intracranial pressure
  2. Septicaemia
  3. Pulmonary aspiration of gastric contents
  4. Major burns
  5. Inhalation of toxic fumes or smoke
  6. Near drowning
  7. D.I.C
  8. Massive blood transfusion
  9. Acute pancreatitis
  10. Radiation injury 

Pathogenesis

IMMUNOLOGIC LUNG DISEASE

Immunologic mechanisms play a crucial role in lung disease as outlined in the table below

Pathophysiology of Restrictive Lung Diseases

Disease

Pathogenesis/pathology

Bronchial asthma

Explain

Hypersensitivity (allergic) pneumonitis

ü Immune mediated inflammation of the lung tissues

ü Examples – Farmer’s lung, Bird breeders lung, Malt workers lung, Mushroom workers lung

Pulmonary Eosinophilia

ü Immunological meditated lung diseases characterized by infiltration of the lungs and elevated eosinophil counts e.g. Loeffler’s syndrome 

Good Pastures Syndrome

ü Necrotizing haemorrhagic interstitial pneumonitis

 

VASCULAR COLLAGEN DISEASE

Pathogenesis of Restrictive Lung Disease in Vascular Collagen Disease

Disease

Pathogenesis/pathology

Rheumatoid arthritis

ü Pleural effusion

ü Interstitial pneumonitis

ü Rheumatoid pneumoconiosis

S.L.E

ü Pleurisy

ü Pleural effusion

ü Interstitial pneumonitis

ü Pulmonary haemorrhage

ü Vasculitis



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Topic 3: Summary

In this topic we have covered;

  1. Respiratory failure.
  2. Atelectasis.
  3. Obstructive lung disease (Asthma)
  4. Restrictive lung disease.

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Topic 3: References

  1. Kishasha M (2016). Textbook of human pathology. 1st edition, Acrodile publishers, Nairobi, Kenya.
  2. Harsh M (2014). Textbook of Pathology. 1st edition. New Delhi: Jaypee Brothers, Medical Pub, India
  3. Ngton C, & Muir (2014). Textbook of Pathology. 15th edition, New Delhi. Jaypee Brothers, India

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Topic 4: PULMONARY INFECTIONS (BACTERIAL PNEUMONIA)

 INTRODUCTION

 Respiratory tract infections are more frequent than any other infections. Majority of  the upper respiratory tract infections (URTIs) are caused by viruses (common cold, pharyngitis) while bacterial, viral, mycoplasmal and fungal infections of the lung (pneumonia).Acute and chronic pulmonary infections which are frequent causes of death are common at all ages and occur when normal lung or systemic defence mechanisms are impaired. They are caused by a wide range of microorganisms.

 Pulmonary defence mechanisms consist of nasal, tracheobronmchial and alveolar mechanisms to filter, neutralize and clear inhaled organisms and particles from the lungs. Impairment of the defence mechanisms includes -

  1. Loss or decreased/suppression of cough reflex leading to aspiration e.g. In coma, neuromuscular disorders, anaesthesia, drug effects or chest pain  
  2. Injury to mucociliary apparatus by cigarette smoking and gaseous inhalation, genetic disorders, inhalation of corrosive substances
  3. Decreased phagocytic or bactericidal function of the alveolar macrophages due to smoking, alcohol and oxygen toxicity.
  4. Pulmonary oedema or congestion (congestive cardiac failure)
  5. Accumulation of secretions e.g. Post-operative , cystic fibrosis and bronchial obstruction

 Defective innate immunity (neutrophil and complement defects) and humoral immunodeficiency) result in increased incidence of infections with pyogenic bacteria. Defects in cell mediated immunity lead to increased infections with intracellular microbes e.g. mycobacterium and herpes viruses and Pneumocystis carinni

 DEFINITION

 Pneumonia is inflammation of the lung parenchyma distal to the terminal bronchioles (respiratory bronchiole, alveolar ducts, alveolar sacs and alveoli) characterized by vascular changes and exudation of fluid and cells. The term pneumonia refers to inflammation of the lungs while consolidation (solidification) describes the macroscopic and radiological appearance of the lungs in pneumonia. The inflammation may reach the pleural surface causing irritation and inflammation of the pleura and accumulation of fluid exudate (pleural effusion). The process is influenced by the spongy character of the lung that allows unimpeded spread of the inflammatory exudate filling the alveolar and affected portions of the lung become relatively solid (consolidation).

 PATHOGENESIS

 The normal lung is protected by a number of defence mechanisms at different levels. These mechanisms include nasopharyngeal filtering action, mucociliary action of the lower respiratory airways, phagocytosing alveolar macrophages and immunoglobulins. Failure of the defence mechanisms and presence of predisposing factors result in development of pneumonia. Such situations include -

 a)      Altered consciousness

 Oropharyngeal contents can be aspirated into the lungs in states of unconsciousness e.g. coma, cranial trauma, seizures, cerebro-vascular accidents, drug overdose and alcoholism.

b)      Depressed cough and gag reflexes

 Allows aspiration of gastric contents e.g. in old age, pain from trauma, thoraco-abdominal surgery, neuromuscular disease, malnutrition, kyphoscoliosis, severe obstructive pulmonary disease, endotracheal intubation and tracheostomy

c)      Impaired mucociliary transport

 Impairment or destruction of the mucous-covered ciliated epithelium as in cigarette smoking, respiratory viral infections, immotile cilia syndrome, inhalation of hot or corrosive gases and old age.

d)      Impaired alveolar macrophage function

 Cigarette smoking, hypoxia, starvation, anaemia, pulmonary oedema and viral respiratory infections.

e)      Endobronchial obstruction

 Interferes with effective clearance of the bronchial tree

 Results from tumours, foreign body, cystic fibrosis and chronic bronchitis

f)       Leucocyte dysfunctions

Congenital and acquired immunodeficiency, HIV/AIDS and granulocyte abnormalities.

ROUTES OF INFECTION

The microorganims gain entry into the lungs via: -

  1. 1.      Inhalation of microbes present in the air
  2. 2.      Aspiration – naso and orophartnx
  3. 3.      Haematogenous spread from a distant foci of infection
  4. 4.      Direct spread from an adjacent site of infection

CAUSES OF PNEUMONIA

Type of Pneumonia

Causes

Community acquired acute pneumonia

ü Streptococcus pneumoniae

ü Haemophilus influenzae

ü Moraxella catarrhalis

ü Staphylococcus aureus

ü Legionella pneuomophila

ü Enterobacteriae – (Klebsiella pneumoniae) and Pseudomonas spp 

Community acquired atypical pneumonia

ü Mycoplasma pneuominaie

ü Chlamydia spp (C. pneumoniae, C. psittaci, C. Trachomatis

ü Coxiella burnetti (Q-fever)

ü Virues – Respiratory syncitial virus, parainfluenzae (children), infleunzae A and B (adultrs) adenovirus

Nosocomial pneumonia

ü Gram Negative rods – Enterobacteraie (Klebsiella spp; Serratia marcescens; Escherichia coli) and Pseudomonas

ü Staphylococcus aureus 

Aspiration pneumonia

ü Anaerobic flora (Bacteroids, Fusobacterium) mixed with aerobic bacteria (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus infleunzae, Pseudomonas  aeruginosa)

Chronic pneumonia

ü Nocardia

ü Actinomyces

ü Granulomatous – Mycobacterium tuberculosis and atypical mycobacteria, Histoplasma capsulatum, Blasotmyces dermatitidis

Necrotizing pneumonia and Lung abscess

ü Anaerobic bacteria

ü Staphylococcus aureus

ü Klebsiella pneumoniae

ü Streptococcus pyogenes

Pneumonia in the immunocompromised host

ü Cytomegalovirus

ü Pneumocystis jeroveci

ü  

 

CLASSIFICATION

Classification is based on: -

1.      Aetiologic classification (Microbiological classification)

  1. Bacterial – pneumococci, streptococci, staphylococcus, H. influenzae, Mycobacterium tuberculosis, anaerobic bacteria – bacteroids
  2. Viral – adeno viruses, pircona viruses, rhino viruses, arbo viruses, coxsackie, myxovirus, myxovirus parainfluenzae, respiratory syncitial virus and psittacosis virus
  3. Rickesttsiae – Coxella burnetti
  4. Protozoa - Pneumocystis carinni, Toxoplasma gondii
  5. Mycoplasma – Mycoplasma pneumoniae
  6. Fungal – Candida albicans, Histoplasmosis, Coccidomycosis, Cryptokocosis (Cryptococcus neofomans), Apsergilus fumigutus (aspergillosis, aspergiloma)
  7. Chemical – kerosene, aspiration, lipid pneumonia

2.      Pathologic classification  – how the infection spreads within the lung

  1. Lobar pneumonia
  2. Bronchopneumonia

 3.      Clinical classification – circumstances surrounding development of disease

  1. Community acquired disease
  2. Hospital acquired (nosocomial) infections
  3. Post-operative pneumonia
  4. Aspiration pneumonia
  5. Obstructive pneumonia
  6. Disease acquired in special environments
  7. Disease in immunosuppressed patients

 PREDISPOSING FACTORS

  1. Viral infections
  2. Hospitalization
  3. Cigarette smoking
  4. Alcohol excess
  5. Bronchiectasis
  6. Bronchial obstruction
  7. Immunosuppression
  8. Intravenous drug use
  9. Inhalation

 Bacterial Pneumonia

 Bacterial infection of the lung parenchyma is the most common cause of pneumonia or consolidation of one or both lungs. There are two types of acute bacterial pneumonia- lobar pneumonia and bronchopneumonia, which have distinct aetiologic agents and morphologic changes.

 Lobar Pneumonia

 INTRODUCTION

 Lobar pneumonia is an acute bacterial infection of the lobes of the lungs. It may involve a part of the lobe, the entire lobe or even two lobes of one or both the lungs. Lobar pneumonia is more common in males that females at a ratio of 3:1 or 4:1. It often develops after exposure to cold, chronic alcoholism, excessive smoking just to mention a few. Allergy plays an important role in the aetiology and pathogenesis of lobar pneumonia.

 AETIOLOGY

 It is based on aetiologic microbes and there are four types of lobar pneumonia that is: -

 1.      Pneumococcal pneumoniae (Streptococcus pneumoniae) – 90%of lobar pneumonia and it is mainly a community acquired infection. Beta haemolytic streptococcus  is common in children after measles or influenza infections, severely debilitated, elderly and diabetic patients

 2.      Staphylococcus aureus – haematogenous spread and following viral infection

 3.      Pneumonia by gram negative aerobic bacteria – this is less common. Organisms include: - H. influenzae (common in children less than 3 years old and after a preceding viral infection), Klensiella pneumoniae (Frielander’s bacilli), Pseudomonas aeroginosum, Proteus, Escherichia coli

   PATHOGENESIS

 The microbes gain access to the lungs via several routes because of failure of the lung defence mechanisms and presence of the relevant predisposing factors.

 Invasion of the lungs results in inflammation of the alveolar. There is production of inflammatory exudate, which spreads to the adjacent alveoli via the inter-alveolar pores. The infection spreads throughout the entire lobe and the spread is usually seen on the affected lobe.

 The organisms are destroyed by phagocytosis initially by the neutrophils and later macrophages. The cells are driven by positive chemotaxis and they destroy the pneumoniae organisms by first fixing them to the alveolar wall before they engulf them.

 The alveoli are filled up with the inflammatory exudate with trapped air and then the whole lobe is converted into a solid mass (air free) – a process described as consolidation. The lower lobes are affected most.

 PATHOLOGIC CHANGES

 There are four sequential pathologic phases of lobar pneumonia namely: -

  1. Stage of congestion (Initial stage)
  2. Stage of red hepatisation (early consolidation)
  3. Stage of grey hepatisation (late consolidation)
  4. Resolution

 Congestion (Initial Phase)

 The stage of congestion, which lasts 1 – 2 days, represents the early acute inflammatory response to bacterial infection and is characterized by extreme congestion and excessive serofibrinous exudation.  Results from outpouring of protein-rich exudates into the alveoli. It is usually associated with dramatic onset of increased temperature with chills and rigors

 Macroscopy

  1. Enlarged lobe
  2. Heavy
  3. Dark red
  4. Congested
  5. Cut surface – exudate blood stained frothy fluid

 Microscopy

  1. Typical features of acute inflammation
  2. Dilatation and congestion of capillaries in alveolar walls
  3. Oedema fluid
  4. Few red blood cells and neutrophils
  5. Numerous bacteria

 Red Hepatization

 The stage of red hepatisation lasts from 2nd – 4th day and is characterized by liver-like consistency of the lung on cut section due to massive accumulation of polymorphs in the alveolar spaces.

 Macroscopy

  1. Affected lobe is red, firm and consolidated
  2. Cut surface is airless, pink, dry, granular and has liver like consistency
  3. Accompanied by serofibrinous pleurisy

 Microscopy

  1. Oedema fluid replaced by fibrin strands
  2. Marked cellular exudates – neutrophils and extravasations of red blood cells
  3. Many neutrophils with ingested bacteria
  4. Less prominent alveolar septa due to cellular exudation

 Grey Hepatisation

 Grey hepatisation lasts from the 4th – 8th day. It occurs due to accumulation of fibrin in the lung spaces.

Macroscopy

  1. Lobe is firm and heavy
  2. Cut surface is dry, granular and grey in appearance with a liver like consistency
  3. More friable
  4. Change of colour from red to grey begins at the hilum and spreads towards the periphery
  5. Fibrinous pleurisy is prominent

 Microscopy

  1. Numerous and dense fibrous strands
  2. Reduced neutrophils exudation due to disintegration of neutrophils
  3. Fewer red blood cells
  4. Macrophages begin to appear
  5. Thin clear space separates cellular exudates from the septa walls
  6. Polymorph leucocytes present in large numbers and produce a proteolytic enzyme (substance)
  7. Vessel congestion is reduced in the inter alveolar walls
  8. Exudate in pleural space is partially organized

 Resolution

 Resolution begins on the 8th or 9th day if no chemotherapy is administered and is completed in 1 – 3 weeks. Antibiotic therapy induces resolution on about the 3rd day. Resolution proceeds in a progressive manner.

 Macroscopy

  1. The solid fibrinous constituent is liquefied by enzymatic action restoring normal aeration in the affected lobe
  2. Softening of the lobe begins centrally and spreads to the periphery
  3. Exudates is removed by coughing/expectoration,  phagocytosis and liquefaction
  4. Cut surface is grey-red or dirty brown and frothy and  yellow creamy fluid can be expressed on pressing
  5. Resolution of pleural reaction may undergo organization forming a fibrous obliteration of pleural cavity.

 Microscopy

  1. Macrophages are predominant and have engulfed neutrophils and debris
  2. Reduced neutrophils
  3. Granular and fragmented fibrous strands in alveolar spaces
  4. Engorged alveolar capillaries
  5. Progressive removal of fluid content and cellular exudates by expectoration and lymphatics results in restoration of normal lung parenchyma with aeration

 CLINICAL FEATURES

 1.      Sudden onset

2.      Symptoms

  1. Shaking, chills
  2. Hotness of the body
  3. Malaise
  4. Pleuritic chest pain
  5. Dyspnoea
  6. Cough with expectoration – mucoid, purulent or bloody sputum

 3.      Signs

a.       General – fever, tachycardia, tachypnorea, cyanosis

b.      Respiratory system

 INVESTIGATIONS

 1.      Full haemogram – neutrophils leucocytosis, raised ESR

2.      Positive blood cultures

3.      Sputum examination

4.      Chest X-ray – consolidation

 COMPLICATIONS

 Complications arise as a result of delayed resolution and spread (local and blood)

  1. Organization of exudates - occurs in 30% of the cases and results in lung fibrosis. This post-pneumonic fibrosis is called carnification
  2. Pleural effusion
  3. Empyema
  4. Lung abscess
  5. Emphysema
  6. Retention of sputum causing lobar collapse
  7. Pneomothorax
  8. Thromboembolism
  9. Lobar gangrene
  10. Metastatic infection(bacteraemia)
    1. Pericardium – pericarditis, myocarditis, endocarditis
    2. Otitis media, Mastoiditis
    3. Meningitis
    4. Brain abscess
    5. Purulent arthritis
    6. Peritonitis

11.  Renal failure, Multiple organ failure

 Bronchopneumonia

 INTRODUCTION

 Bronchopneumonia is inflammation of the terminal bronchioles that extends into the surrounding alveoli resulting in patchy consolidation of the lungs. It involves both the right and left lung fields. It is particularly frequent at extremes of life (infancy and old age), chronic debilitating diseases and post operatively. The susceptibility in children is due to poor propulsive power (cough reflex), delicate mucosa and a short wide bronchiole tree.

 PATHOGENESIS

 Organisms gain access to the lungs via the bronchioles tree where they affect the bronchioles of both lungs.

 AETIOLOGY

  1. Staphylococcus
  2. Streptococcus
  3. Pneumococci
  4. Klebsiella pneumoniae
  5. Heamophilus influenzae
  6. Gram negative bacilli – Pseudomonas
  7. Coliform bacteria

PATHOLOGY

 Macroscopy

  1. Patsy areas of red or grey consolidation affecting one or more lobes
  2. Involves the lower zones of the lungs due to gravitation of secretions
  3. Bronchioles are extensively inflamed and filled with inflammatory exudates
  4. Consolidation occurs around the bronchioles
  5. Slight peribronchiole thickening
  6. Cut surface shows patchy consolidated lesions with dry, granular, firm red or grey colour, which are 3 – 4 cm in diameter. They are slightly elevated above the surface and can easily be felt by passing fingertips on the cut surface.

 Microscopy

 1)      Acute bronchiolitis

2)      Suppurative exudates containing chiefly of neutrophils

3)      Thickening of alveolar septa by congested capillaries and leucocyte infiltration

4)      Oedema fluid (less in involved alveolar)

5)      Alveoli around the bronchioles undergo absorption, collapse and further out there is compensatory emphysema

  Differences Between Lobar and Bronchopneumonia 

 Feature

Lobar pneumonia

Broncho pneumonia

Definition

Acute bacterial infection of a part of a lobe of one or both lungs or the entire lobe(s)

Acute bacterial infection of the terminal bronchioles extending in to the adjoining alveoli

Age group

More common in adults

Common at extremes of ages – infants and old age

Predisposing factors

More often affects healthy persons

Pre-existing disease

Common aetiologic agents

Pneumococci, Klebsiella pneumonias, Staphylococcus, Streptococcus

Staphylococcus, Streptococcus, Pseudomonas, Heamophilus infleunzae

Pathologic features

ü Congestion (1-2 days)

ü Early (red hepatisation) 2 – 4 days

ü Late consolidation (grey hepatisation) 4 – 8 days

ü Resolution (1 – 3 weeks)

ü Patchy consolidation

ü Alveolar exudation

Investigations

ü Neutrophil leucocytosis

ü Positive blood culture

ü X-ray shows consolidation

ü Neutrophil leucocytosis

ü Neutrophil leucocytosis

ü X-ray shows spotted focal opacities

Prognosis

Good response to treatment, resolution is common, good prognosis

Variable

Prognosis poor

Complications

ü Pleural effusion

ü Empyema

ü Lung abscess

ü Organization

ü Bronchiectasis

ü Pleural effusion

ü Empyema

ü Lung abscess

ü Organization

 

CLINICAL FEATURES

1.      History of preceding bed-riddance, aspiration of gastric contents and upper respiratory tract illness

2.      as lobar pneumonia

  INVESTIGATIONS

 1.      Chest X-ray – shows mottled, focal opacities in both lungs, chiefly in the lower zones

2.      Total Blood counts

 COMPLICATIONS

 1.      as lobar pneumonia

2.      Bronchiectasis


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Topic 4: PULMONARY INFECTIONS (OTHER PNEUMONIAS)

Aspiration Pneumonia

INTRODUCTION

Aspiration pneumonia is a pulmonary sequelae resulting from the abnormal entry of endogenous secretions or exogenous substances into the lower airways. This occurs because of breakdown in defences that protect the tracheobronchial tree (e.g. glottic closure, cough reflex and cleansing mechanisms of the lower respiratory tract) and pulmonary complications that result from the aspiration event.

PREDISPOSING FACTORS

1.      Altered consciousness

  1. Alcoholism
  2. Seizures
  3. Cerebrovascular accidents
  4. Head trauma
  5. General anaesthesia
  6. Drugs

2.      Dysphagia

a.       Oesophageal disorder- Stricture, neoplasia, diverticula, tracheooesophageal fistula and incompetent cardiac sphincter

b.      Neurological disorder - Parkinson’s disease, Myaethenia gravis, Pseudobulbar palsy

 3.      Mechanical disruption of defence barriers  - nasogastric tube, endotracheal intubation and tracheostomy

 4.      Anatomical abnormalities - tracheo-oesophageal strictures, oesophageal strictures, diverticuli, and gastric outlet obstruction e.g. pyloric stenosis,  Pharyngeal anaesthesia

5.      Protracted vomiting

 CLASSIFICATION    

Aspiration pneumonia refers to three distinctive syndromes based on the character of the inoculation, which defines the pathogenesis of pulmonary complications, clinical presentation and treatment. The three syndromes namely chemical pneumonitis, bacterial infection and mechanical obstruction may overlap.

 CHEMICAL PNEUMONITIS

 Introduction

 Chemical pneumonitis refers to fluids that are inherently toxic to the lower airways and can initiate an inflammatory reaction that is independent of bacterial infection. Examples of such fluids include – acids (e.g. gastric acid – most common), volatile hydrocarbons (gasoline, kerosene and animal fats/milk), mineral oil and alcohol.

 Pathogenesis and Pathology

 Acids induce an inflammatory reaction, which is more pronounced at a pH of less than 2.5. Pathologic changes occur with devastating rapidity. After 48 hours the lung is grossly oedematous and haemorrhagic and shows alveolar consolidation. Resolution begins on the 3rd day and may be complete or result in parenchymal scarring.

 Macroscopy

  1. Atelectasis
  2. Peribronchial haemorrhage
  3. Pulmonary oedema
  4. Degeneration of the bronchial epithelium

 Microscopy

  1. Early necrosis of type I alveolar cells
  2. Fibrin
  3. Polymorphonuclear infiltration
  4. Alveolar type II cells degenerate as type I cells necrose further and detach from the basement membrane
  5. Hyaline membrane formation

 Natural History

 Chemical pneumonitis may take three courses namely: -

  1. Rapid improvement within 4 – 5 days
  2. Initial improvement but new extending infiltrations due to pulmonary super infections
  3. A fulminant course with death occurring shortly after aspiration because of  adult respiratory distress syndrome (ARDS).

 Presentation

  1. History of aspiration
  2. Rapid onset of respiratory distress syndrome with cyanosis, tachycardia and tachypnoea
  3. Bronchospasms
  4. Fever
  5. Chest X-ray shows mottled densities located in one or both lower lobes
  6. Lung function
    1. Reduced lung compliance
    2. Abnormal ventilation-perfusion ration
    3. Reduced diffusing capacity
    4. Reduced PO2
    5. Respiratory alkalosis
    6. Hypoxaemia (due to pulmonary oedema, reduced surfactant activity, reflex airway closure, alveolar haemorrhage and hyaline membrane formation)
  7. Metabolic acidosis
  8. Hypotension - reflex reaction and depletion of intravascular volume due to fluid aggregation within the lungs.
  9. Patients with severe aspiration pneumonia progress into adult respiratory distress syndrome (ARDS).

 BACTERIAL INFECTION

 Introduction

 Bacterial infection is the most common form of aspiration pneumonia. Bacteria such as Streptococcus pneumoniae, Heamophilus influenzae, gram-negative bacilli and Staphylococcus aureus are relatively virulent in lower airways and a small inoculation is all that is required for the infection to take root. These pathogens cause pneumonia by microaspiration (aspiration of small volumes). Diagnosis is suspected when a susceptible host develops fever, purulent sputum and a pulmonary infiltrate in a dependent pulmonary segment. 

 Pathology

 The aspirated inoculum is generally composed of oropharyngeal secretions habouring bacteria from various sources in the upper airway. The infections are polymicrobial flora with the principal pathogens being anaerobic bacteria. Aerobic pathogens are present too while gram-negative bacilli are common in patients with hospital acquired aspiration pneumonia.

 Presentation

 It takes a variety of pathologic forms with the initial lesion is pneumonitis, an inflammatory reaction in the pulmonary parenchyma. After 7 – 14 days from the onset of the initial episode, there is suppuration, lung abscess, necrotizing pneumonia and empyema.

 Anaerobic pneumonitis is one of the few bacterial pneumonias that cause chronic symptoms such as chronic fatigue, malaise, fever, weight loss and anaemia. In acute form there may be multiple pulmonary cavities resulting in pulmonary gangrene or necrotizing pneumonia or very large lung abscesses with life threatening complications.

 MECHANICAL OBSTRUCTION

 Mechanical obstruction is sequelae of aspirating fluids or particulate matter that are not inherently toxic to the lung but can cause airway obstruction or reflex airway closure.

 Fluids

 Fluids that are not inherently toxic to the lungs include saline, barium, water and gastric content with a pH exceeding 2.5.

 Solid Particles

 The effects and severity of mechanical obstruction depends on the size the particle and the level of obstruction. Large objects obstruct the trachea and larynx causing sudden respiratory distress, aphonia, cyanosis and death. It is very common in children during the oral stage. The particles involve the usual objects such as peanuts, vegetable particles, inorganic material, and teeth just to mention a few. The vegetable materials are bad because they swell due to their hydroscopic properties and the undigested cellulose cats as a local irritant causing inflammation.

 Aspiration of a large material causing sudden respiratory distress is referred to as café coronary when one aspirates a big chunk of meat at a restaurant dinner because it resembles the effects of myocardial infarction. On-scene resuscitation is Heimlich manoeuvre. Aspiration of small particles causes less severe process because of partial or complete obstruction of the smaller airways.

 The initial symptom is cough and involvement of major bronchi results in wheeze, dyspnoea, cyanosis, chest pain, vomiting, atelectasis and obstructive emphysema. Bacterial infection mainly by anaerobic bacteria from the oropharynx is a frequent complication of lower airway obstruction that persists for 1 – 2 weeks or more  

Hypostatic Pneumonia

Pneumonia that occurs as a result of collection of oedema fluid and secretions in dependent zones of the lungs. The fluid then gets infected by bacteria from the upper respiratory tract. It is common in severely debilitated, bed-ridden patients, old and feeble and comatose patients.

Nosocomial (Hospital-Acquired) Pneumonia

Introduction

These are hospital-acquired pulmonary infections, acquired in the course of stay in the hospital. Nosocomial pneumonia is a new episode of pneumonia occurring at least 2 days after admission to hospital. It encompasses post-operative and certain forms of aspiration pneumonia. They are common in patients with severe underlying disease, immunosuppression, prolonged antibiotic therapy or invasive devices and procedures e.g. intravenous catheters. They are life-threatening infections.

Organisms

  1. Gram negative rods – Enterobacteriae – Klebsiella., E. coli, Pseudomonas spp, Proteus, Serratia
  2. Staphylococcus aureus
  3. Pneumococcus
  4. Legionella 

Factors Predisposing to Nosocomial Pneumonia

  1. Reduced Host defence
    1. Reduced immune defence (steroid treatment, malignancy, diabetes)
    2. Reduced cough reflex e.g. post operative
    3. Disordered mucociliary clearance e.g. anaesthetic agents
    4. Bulbar or vocal cord palsy
  2. Aspiration of nasopharyngeal or gastric secretions
    1. Immobility
    2. Reduced consciousness
    3. Vomiting, dysphagia, achalasia or severe reflux
    4. Nasogastric intubation
  3. Bacteria introduced into the lower respiratory tract
    1. Endotracheal intubation
    2. Tracheostomy
    3. Infected ventilators/nebulizers/bronchoscopes
    4. Dental or sinus infection
  4. Bacteraemia
    1. Abdominal sepsis
    2. Infected emboli
    3. Intravenous cannula infection

Differential Diagnosis of Pneumonia

  1. Pulmonary infarction
  2. Pulmonary/pleural tuberculosis
  3. Pulmonary oedema
  4. Inflammatory conditions below the diaphragm


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Topic 4: PULMONARY INFECTIONS (LUNG ABSCESS)

Lung abscess is a collection of pus within a destroyed portion of the lung following a pulmonary infection with parenchymal necrosis. Lung abscess is a localized area of necrosis of lung tissue with suppuration that is usually solitary but occasionally multiple in necrotizing pneumonia.  The overlap of aspiration pneumonia, lung abscess and necrotizing pneumonia results in empyema (collection of pus within the pleural cavity).

 CLASSIFICATION

 There are two types of lung abscess namely primary and secondary lung abscess

 Primary lung abscess

 Primary lung abscess develops in a normal lung commonly following aspiration of infected material. It forms single large abscess frequent at the lower part or the apex of the right lobe.

 Secondary lung abscess

 Secondary lung abscess develops as a complication of other lung diseases or from another site. They are mostly small and multiple post-pneumonic or septic emboli.

 PREDISPOSING FACTORS

  1. Pulmonary infections such as bronchitis, bronchopneumonia and lobar pneumonia
  2. Cachexia/emaciation
  3. Malnutrition
  4. Otitis media
  5. Chronic alcoholism
  6. Chronic nephritis
  7. Smoking
  8. Malignancy

 AETIOLOGY

  1. Bacteria - Streptococcus pyogenes (Group A b-haemolytic), Streptococcus pneumonia, Staphylococcus aureus, Anaerobic bacteria, Entero Gram negative bacteria – Klebsiella, Mycobacterium – Mycobacterium tuberculosis, Pseudomonas aeruginossa, Pseudomonas pseudomallaei, Legionella, H. Influenza, Nocardia
  2. Actinomycosis
  3. Fungi – Cryptococcus neoferan, Aspergillus, Histoplasma capsulatum
  4. Parasites – Entamoeba histolytica

 MECHANISM OF INFECTION (PATHOGENESIS)

 A.       Preceding Bacterial Infections (inoculation)

 This follows infection of pre-existing cavities in the lung for example in pneumonia, bronchiectasis and tuberculosis. It is common in debilitated patients with culprit organisms being Strep. pneuminaie; Strep. pyogenes and Staph. aureus  

 B.        Aspiration/inhalation of infected matter

 Aspiration of infected foreign material such as food, decaying teeth, gastric contents, severely infected gingivae and teeth and any necrotic tissue from the mouth and upper respiratory tract (pharynx and larynx and nasopharynx). This commonly affects the right lung (why?)

Aspiration results from reduced level of consciousness and reduced gag reflex as seen in alcoholism, drug addiction, during sleep, general anaesthesia, seizure disorders, neurologic disorders, dysphagia (oesophageal disorders and neurologic disorder), general debility and disruption of mechanical barriers. It affects the lower part of the upper lobe or upper part of the lower lobe.

C.        Bronchial obstruction - Obstruction results in development of an abscess distal to the site of obstruction

D.       Septic emboli - The septic emboli originates from pyaemia, thrombophlebitis and bacterial endocarditis

E.        Miscellaneous

  1. Infection of pulmonary infarcts
  2. Amoebic abscess
  3. Trauma to lung (penetrating chest injuries)
  4. Direct extension from suppuration in the mediastinum, oesophagus; subphrenic region and spine

PATHOPHYSIOLOGY

Inoculation and aspiration provide access of the pathogens to the lung. Inoculation follows periodontal infection while aspiration occurs when conscious level is reduced resulting in an ineffective gag reflex. Alcoholism, drug addiction, general anaesthesia, seizure disorders, sedation, neurological disorders, oesophageal disorders and disruption of mechanical barriers facilitate aspiration of infected foreign material. Pneumonitis/aspiration pneumonia involves dependent pulmonary segments as a result of gravitational flow. 

PATHOLOGY

Macroscopy

  1. Variable size of abscesses
  2. Cavities with poorly ragged walls containing exudate
  3. Acute pneumonic process surrounds the abscess
  4. Fibrous wall develops in chronic structures
  5. Thrombosis of vessels may occur leading to massive ischaemic necrosis (infarction)

Microscopy

  1. Destruction of lung tissue
  2. Suppurative exudate
  3. Lymphocytes, plasma cells and macrophages
  4. Damaged alveolar walls
  5. On chronic states – fibroblastic proliferation

 CLINICAL FEATURES

  1. Fever (high remittent pyrexia)
  2. Malaise
  3. Weight loss
  4. Cough with purulent/putrid expectoration
  5. Chest pain
  6. Haemoptysis
  7. Finger clubbing
  8. Anaemia
  9. Respiratory features depending on state of infection

 DIAGNOSIS

  1. History
  2. Physical examination
  3. Investigations
    1. Chest X-ray – opacity, cavity filled with air-filled level
    2. Cultures – blood, pleural fluid, pus
    3.  Blood counts

SEQUALE OF LUNG ABSCESS

  1. Healing – small abscess
  2. Empyema – subpleural abscess spread
  3. Broncopleural fistula
  4. Haemorrhage – due to erosion of pulmonary blood vessels
  5. Meningitis – blood spread
  6. Cerebral abscess – blood spread

COMPLICATIONS

  1. Pleural effusion
  2. Empyema
  3. Haemorrhage
  4. Septic embolization
  5. Secondary amyloidosis


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Topic 4: PULMONARY INFECTIONS (PULMONARY TB)


Tuberculosis (abbreviated as TB for tubercle bacillus or Tuberculosis) is a common and often deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis.  Tuberculosis usually attacks the lungs (as pulmonary TB) but can also affect the central nervous system, the lymphatic system, the circulatory system, the genitourinary system, the gastrointestinal system, bones, joints, and even the skin. Other mycobacteria such as Mycobacterium bovis, Mycobacterium africanum, Mycobacterium canetti, and Mycobacterium microti also cause tuberculosis, but these species are less

Pulmonary tuberculosis is a chronic communicable lung disease, which is the classical and most common example of chronic infection of the lung. Tuberculosis is made distinctive by a necrotizing (caseating) granulomatous tissue response to seeded organisms (it exhibits a granulomatous inflammation).

EPIDEMIOLOGY

World Health Organization (WHO) estimates that nearly 2 billion people (one third of the world's population) have been exposed to the tuberculosis pathogen and annually, 8 million people become ill with tuberculosis and 2 million people die from the disease worldwide. In 2004, around 14.6 million people had active TB disease with 9 million new cases. Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/.

The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis with the emergence of drug-resistant strains also contributing to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs. The rate at which new TB cases occur varies widely, even in neighboring countries, apparently because of differences in health care systems.

The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults; however, in developed TB is mainly a disease of older people, or of the immunocompromised.

Chest Radiograph in TB

CAUSATIVE AGENT

 The tuberculous bacilli or Koch’s bacilli discovered by Robert Koch in 1882 cause tuberculosis.  Mycobacterium tuberculosis causes tuberculosis in the lungs and other tissues of the human body. The organism is a strict aerobe that thrives best in high oxygen tension areas like the apex of the lung. Mycobacteria are acid-fast, slender rod, aerobic, non-motile, non-capsulated and non-sporing organisms

 Mycobacterium tuberculosis is a species of the genus mycobacterium, family mycobacteriaceae, non-sporulating, aerobic acid-fast rods. They have slow growth with the colonies being opaque, dry, off-white to cream coloured at an optimal temperature of 37oC. Because the tubercle bacillus has a capsule composed of waxes and fatty substances, it is more resistant to destruction than many other organisms.

 TRANSMISSION

Introduction

People suffering from active pulmonary TB cough, sneeze, speak, or spit, expelling infectious aerosol droplets 0.5 to 5 µm in diameter. A single sneeze can release up to 40,000 droplets. Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very low and the inhalation of just a single bacterium can cause a new infection.

People with prolonged, frequent, or intense contact are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis can infect 10–15 other people per year.  Others at risk include people in areas where TB is common, people who inject drugs using unsanitary needles, residents and employees of high-risk congregate settings, medically under-served and low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, patients immunocompromised by conditions such as HIV/AIDS, people who take immunosuppressant drugs, and health care workers serving these high-risk clients.

Transmission can only occur from people with active (not latent) TB and the probability of transmission from one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of exposure, and the virulence of the M. tuberculosis strain.

The chain of transmission can, therefore, be broken by isolating patients with active disease and starting effective anti-tuberculous therapy. After two weeks of such treatment, people with non-resistant active TB generally cease to be contagious. If someone does become infected, then it will take at least 21 days, or three to four weeks, before the newly infected person can transmit the disease to others.  TB can also be transmitted by eating meat infected with TB. Mycobacterium bovis causes TB in cattle. (See details below.)

Modes of transmission

 1.      Inhalation

Majority of patients acquire the infection through inhalation of airborne infected droplets derived from the sputum of an adult with cavitary pulmonary tuberculosis produced by the coughing or sneezing of infected individuals

Can be in fresh cough droplets or in dried sputum

2.      Ingestion

Ingestion from self-swallowing of infected sputum of an open case of pulmonary tuberculosis or ingestion of bovine tubercle bacilli from milk of diseased cows resulting in tonsilar or intestinal tuberculosis.

Ingestion is nowadays rare due to pasteurization of milk

3.      Inoculation

TB organisms may gain entrance into the boy by direct inoculation of organisms through the skin e.g. in laboratory accidents or post mortem examination

4.      Transplacental (rare)

The term infection connotes multiplication of tubercle bacilli in the tissues with the induction of an immunological response. Presence of tubercle bacilli within the body can be detected by tuberculin skin test, demonstrate bacilli or their products in body secretions, or infected tissues.

PREDISPOSING FACTORS

1.      Debilitating or immunosuppressive conditions

  1. Diabetes mellitus
  2. Chronic lung disease
  3. End stage renal disease
  4. HIV/AIDS
  5. Alcoholism
  6. Hodgkin’s disease

2.      Smoking

3.      Inadequate medical care

4.      Poverty

5.      Crowding

6.      Malnutrition

IMMUNOLOGY

Introduction

Immunity in tuberculosis may be either natural or acquired. Acquired immunity is intimately associated with development of allergy (hypersensitivity). Hypersensitivity (allergy) and immunity play as significant role in development of lesion in tuberculosis.

The tubercle bacilli do not produce anti toxins and tissue changes seen in tuberculosis are because of host response to the organism, which leads to development of cell-mediated hypersensitivity (type IV) and immunity. These responses are due to the presence of several lipids such as mycosides and glycoproteins. Myosides are essential for growth and virulence of the organism in the animals and glycosides, which are present in the mycobacterium wall act as adjuvant acting along with tuberculoproteins.

The basic tissue elements responsible for immunity are the macrophages which phagoctose and destroy tubercle bacilli and caseous necrosis in which the bacilli are destroyed in large numbers. This is because the macrophages take part in chemical mechanisms involved in cellular immunity.

Tissue reaction to tubercle bacilli varies in healthy individuals (primary infection) and previous infected individuals (secondary infection). In primary infection, introduction of tubercle bacilli into the skin evokes no visible reaction for 10 – 14 days. After this period, a node develops at the inoculation site. This eventually ulcerates and heals. The regional lymph nodes develop tubercles, which is a manifestation of delayed hypersensitivity reaction. In secondary infection, the tubercle bacilli are injected into the skin and in 1 -2 days the inoculation site is indurated and dark attaining a diameter of one cm. the skin lesion ulcerates and heals quickly and the regional lymph nodes are not affected (Koch’s phenomenon).

Hypersensitivity and immunity responses are initiated by T lymphocytes sensitized against specific antigens in tuberculin. Because of this sensitization, lymphokines are released from T-cells, which induce an increase in microbicidal activity of the macrophages.

Immune properties of the solid caseum are converted suddenly to a highly fertile environment for intense bacterial propagation at the onset of liquefaction characterizing the sequence of pathologic events of progressive clinical pulmonary tuberculosis.

Effectiveness of immune mechanisms that are responsible for bacillary destruction are influenced by: -

  1. Environmental factors
  2. Hereditary factors
  3. Developmental factors – infancy, puberty and senility
  4. Race
  5. Nutrition
  6. Stress
  7. Cellular immunodeficiency
  8. Diabetes
  9. Sarcoidosis

Predominance of immune forces over tubercle bacilli despite liquefaction and spread of the disease allow ultimate and effective containment and destruction of the bacilli.   

 Acquired Immunity and Hypersensitivity

 Hypersensitivity (allergy) and acquired immunity in tuberculosis vary and independent but appear concurrently.

 Acquired Immunity

 Acquired immunity is mediated through cellular and biochemical mechanisms linked with delayed hypersensitivity. The mediation is via small antigen-responsive lymphocytes, which after initial infection with tubercle bacilli become immunologically committed cells.

 Further interaction of sensitized lymphoid cells with bacilli results in formation of potent molecules that cause several important immunologically oriented behaviour of cells in the cellular defence system. The immuno-competent cells initiate an immune respsone, have a long circulating life span, are in constant motion through lymphoid tissue to the blood, and back again.  

 The effector molecules, which are the lymphokines (cytokines) include -

  1. Migration inhibition factor (inhibits migration of macrophages)
  2. Macrophage activating factor (enhance metabolism and functional capacity)
  3. Mitogenic and lymphocyte activating factor (induce blastogenesis and cell division of lymphocytes)
  4. Lymphotoxin (a cytotoxic material)
  5. Chemotaxin factors – attract neutrophils and monocytes

 Artificial Acquired Immunity

 Artificial acquired immunity is induced by vaccination using a live attenuated mycobacterium organism (BCG)

 Natural Immunity

 Rare/varies with race

 Tuberculin (Mantoux) Skin Test

 Intradermal injection of 0.1 mls of tuberculoprotein, purified protein derivative (PPD). A delayed hypersensitivity reaction (DHR) develops in individuals previously infected with tuberculous infection. The reaction is identified as an indurated area of > 15 mm in 72 hours. Patients with disseminated tuberculosis may show negative test due to release of a large amount of tuberculoproteins from the endogenous lesion masking the hypersensitivity test. 

 A positive test indicates a cell mediated hypersensitivity to tubercular antigens but does not distinguish between infection and disease. False positive results occur in atypical mycobacterium infection while false negative test may be associated with sarcoidosis, viral infection, Hodgkin’s disease and fulminant tuberculosis.

 Immunization against Tuberculosis

 This is achieved by injection of attenuated strains of bovine type of tubercle bacilli, Bacilli Calmette Guerin (BCG). Cell mediated immunity with consequent delayed hypersensitivity reaction develops with healing of the lesion. The cell-mediated immunity persists rendering the host tuberlin positive and hence immune.

 PATHOGENESIS

 Introduction

TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within the endosomes of alveolar macrophages. The primary site of infection in the lungs is called the Ghon focus usually located in either the upper part of the lower lobe, or the lower part of the upper lobe. The bacteria are picked up by dendritic cells, which do not allow replication but can transport the bacilli to local (mediastinal) lymph nodes.

Further spread is through the bloodstream to other tissues and organs where secondary TB lesions can develop in other parts of the lung (particularly the apex of the upper lobes), peripheral lymph nodes, kidneys, brain, and bone. All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid.

Classification

Tuberculosis is classified as one of the granulomatous inflammatory conditions in which macrophages, T lymphocytes, B lymphocytes and fibroblasts aggregate to form a granuloma, with lymphocytes surrounding the infected macrophages. The granuloma prevents dissemination of the mycobacteria and provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes (CD4+) secrete cytokines such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected. T lymphocytes (CD8+) can also directly kill infected cells.

Importantly, bacteria are not always eliminated within the granuloma, but can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of cell death, also called necrosis, in the center of tubercles.

If TB bacteria gain entry to the bloodstream from an area of damaged tissue they spread through the body and set up many foci of infection, all appearing as tiny white tubercles in the tissues. This severe form of TB disease is most common in infants and the elderly and is called miliary tuberculosis. Patients with this disseminated TB have a fatality rate of approximately 20%, even with intensive treatment.

In many patients the infection tissue destruction and necrosis are balanced by healing and fibrosis and the affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are joined to the air passages bronchi and this material can be coughed up. It contains living bacteria and can therefore pass on infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.

Lesions in PTB

 The basic types of tissue change in tuberculosis include -

  1. Exudative lesion
  2. Caseation and cavity formation
  3. Tubercle or granuloma formation
  4. Non-specific lesions

 Exudative Lesions

 The lung is the most often site of primary lesion in tuberculosis. The earliest reaction to the tubercle bacilli is a pre-exudative dilatation of alveolar capillaries with moderate swelling of alveolar endothelial cells. The swollen alveolar endothelial cells contain limited numbers of phagocytized tubercle bacilli. The exudative phase follows rapidly and forms three patterns: -

 1.      Fibrinomacrophagic alveolitis

Many tubercle bacilli are seen within the mononuclear macrophages in the alveolar lumen plus fibrin and some extracellular bacilli

Polymorphonuclear cells are seen in the alveoli

The lesion is very prone to caseation

2.      Polymorphonuclear alveolitis

There is predominance of polymorphonuclear cells

Fibrin and oedema are present

A large number of tubercle bacilli are seen through the lesion

The lesion rarely caseates but is prone to liquefaction

Rarely seen in primary tuberculosis

3.      Fibrinous alveolitis

This is not seen in primary infection

Fibrin is present with few or no cellular elements and tubercle bacilli

It is prone to caseation

The polymorphonuclear response is more often provoked when the infection is massive or when host susceptibility is great. The extent and duration of primary exudative response depends on the number of bacilli present, native resistance of the host and onset of hypersensitivity.

During this phase, the alveolar structure is preserved as the bacilli are multiplying. The lesions undergo almost complete resolution and onset of caseous necrosis heralds a change in reaction of the tissues towards the bacilli causing disruption of the alveolar structure and hypersensitivity or allergy producing changes in behaviour and morphology of the infected tissues.

Caseation and Cavity Formation

Caseation is a type of necrosis (flavoured cheese made of sheep or goat’s milk) is characteristic of tuberculosis. The tubercle bacilli reduce in number following their destroyed in the caseum, which is the site of tremendous bacillary destruction. The number of bacilli and the extent of exudation influence the magnitude of necrosis.

Caseation is an expression of hypersensitivity and cellular immunity. The behaviour of the caseum is critical and determines progression of tuberculosis as disease. The caeous (cheesy) material may undergo two processes (1) it may remain solid and undergo localization, resorption, hyaline degeneration, fibrosis and if the necrotic material is large – calcification or ossification (this changes are associated with reduction in the number of tubercle bacilli and eventual sterilization) and (2) may soften and liquefy (less frequent occurrence)

Softening and liquefaction of the caseous material is associated with large areas of caseation, invasion by polymorphonulcear cells and appearance of proteolyic enzymes. Stimulated macrophages play a role in this process as they produce a plasminogen activator (plasmin system). Softening is accompanied by intense multiplication of tubercle bacilli.

The liquefied caseum empties into a bronchus with intralobular dissemination of bacilli into other parts of the lung. The lesion, which has sloughed off its contents into the bronchus, is now a cavity.  Atmospheric oxygen now has access to the lumen of the cavity where bacillary proliferation continues in the necrotic inner zone. A capsule of granulation tissue and fibrous tissue that surrounds the necrotic inner circle contributes to the chronicity of the tuberculous cavity. Without treatment, few cavities heal and remain open sources of multiplying tubercle bacilli.   

Tubercle or Granuloma Formation

Tubercle or granuloma formation may proceed or follow necrosis. Polymorphonuclear and mononuclear macrophages (from blood monocytes and local tissues) appear and continue to phagocytose tubercle bacilli at the periphery of the lesion. This type of inflammatory response that involves chiefly mononuclear cells is described as granulomatous inflammation in contrast to polymorphonuclear response to pyogenic organisms.

The macrophages undergo structural changes because of immune mechanisms. They increase in size, cytoplasm becomes pale and oesinophilic and their nuclei become elongated and vesicular. This makes the macrophages resemble epithelial cells (are then called epitheloid cells).

Macrophages continue entering the tissues from circulating monocytes or local proliferation, undergo changes to form more epitheloid cells, and with time adjacent epitheloid cells aggregate into tight clusters or granulomas. Release of cytokines in response to sensitized CD4+ cells and constituents of the mycobacterium cell wall facilitate formation of granulomas.

Some macrophages divide atypically of may coalesce to form multinucleated giant cells of Langhan’s type. Simultaneous with the cellular reactions, new capillaries, lymphocytes, fibrobroblasts and collagen tissue appear to encircle the entire area of epitheloid cells and caseation appears in the centre enhancing granuolma formation. This forms a hard tubercle. Within 10 – 14 days, the centre of the cellular mass begins to undergo caseation necrosis exhibited by cheesy appearance and high lipid content. This results in formation of the soft tubercle, which is the hallmark of tuberculous lesions.

Caseation necrosis results from interaction of mycobacterium with a activated T cells (CD4+ helper cells and CD8+ suppressor cells) and direct toxicity of mycobacterium on macrophages. The soft tubercle, which is a fully developed granuloma with caesous centre, does not favour rapid proliferation of tubercle bacilli.


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Topic 4: PULMONARY INFECTIONS (PULMONARY TB Cont')

FATE OF GRANULOMA

1.      Cold abscess - Caseous material undergoes liquefaction and extends into surrounding soft tissue discharging content on the surface. It is called a cold abscess because there are no pus cells.

2.      Sinus formation

Sinuses are formed in tissues such as bones, joints, lymph nodes and epididymis

Sinus tracts are lined by tuberculous granulation tissue

3.      Coalesce of adjacent granulomas and progressive fibrosis

4.      Dystrophic calcification

 Non-specific Changes

  1. Inflammatory response
  2. Oedema formation
  3. Cellular reactions
  4. Haemorrhage

 PATTERNS OF PROGRESSION AND DISSEMINATION

 Patterns of progression and dissemination of tuberculosis are -

 1.      Direct extension

 Direct extension depends on population of bacilli, vascularity of tissues involved and susceptibility of the host. If bacterial multiplication and dissemination is rapid, the exudative phase will progress rapidly by direct extension with a similar spread of the exdutaive lesion.

  2.      Ductal or intracanalicular dissemination

 Ductal or intracanalicular dissemination is very important in pulmonary tuberculosis. It occurs in conjunction with liquefaction of the caseum and sloughing off the highly infective material into the bronchi. The sloughed material is carried to other parts of the lung.

Sloughed tubercle bacilli are present in the sputum and are carried to the mucous membranes e.g. the larynx, mouth, pharynx, nose and middle ear. The organisms may be swallowed into the gastrointestinal tract resulting in intestinal tuberculosis or peritoneal abscess and fistula.

3.      Lymphogenous dissemination

The great number of lymphatic channels in the lungs provides many opportunities for dissemination of tubercle bacilli. This type of dissemination is more common and extensive in children.

New lesions are formed along lymph vessels but more conspicuous in lymph nodes. From the lymphatics, the tubercle bacilli gain access into the blood stream. It is responsible for pleural involvement, lesions in the chest wall, spine, small bowel and abdomen.

4.      Haematogenous dissemination

Tubercle bacilli may be carried into the blood stream in various ways such as: -

a.    Rupture of liquefied caseous material into a pulmonary vein

b.    Mediastinal lymph nodes in primary tuberculosis

c.    Caseous foci in extra pulmonary organs

5.      Dissemination in serous cavities

 In the pleural, peritoneal and pericardial cavities the tubercle bacilli may be seeded from a liquefying caseous focus on the surface of an organ or structure that lies in or adjacent to such as a serous space.

 TYPES OF TUBERCULOSIS

 The lung is the main organ affected in tuberculosis. Based on tissue response and age the infection with tubercle bacilli is of two main types: - primary and secondary infection.

 Primary Infection

 Introduction

 Primary pulmonary infection occurs usually in children lacking previous exposure to tubercle bacilli or vaccinated against it. It begins as a single granulomatous lesion called Ghon focus, which is subjacent to the pleura in the inferior upper lobe or superior lower lobe regions.

 Primary or Ghon’s Complex

 Primary complex or Ghon’s complex is the lesion produced at the portal of entry with foci in the draining lymphatic vessels and lymph nodes. Tissues involved are mainly the lungs and hilar lymph nodes. Other tissues that may be involved are the tonsils, cervical lymph nodes, small intestine and mesenteric lymph nodes. Dissemination from primary tuberculosis is high in immunosuppresed hosts as in HIV/AIDS patients.

 The primary complex or Ghon’s complex in the lungs consists of three components: -

  1. Pulmonary component (Ghon focus)
  2. Lymphatic vessel component
  3. Lymph node component (Hilar)

Pulmonary Component (Ghon’s Focus)

The Ghon’s focus is the lesion in the lungs that is a 1 -2 cm diameter solitary area of tuberculous pneumonia located under the pleura in the lower part of the upper lobe. It forms at the subpleural region in the midzone of the lung.

Lymphatic Vessel Component

The lymphatic vessels draining the lung lesion contain phagocytes containing the bacilli. They may develop beaded, military tubercles along the path of hilar lymph node.

Lymph node component

The lymph node component consists of enlarged hilar and tracheo-bronchial lymph nodes in the area drained. The affected lymph nodes are matted and show caseation necrosis.

In case of involvement of the intestines, a small primary focus occurs in the intestine with enlarged mesenteric lymph nodes producing tabes mesenterica. Enlarged and caseous mesenteric lymph nodes may rupture into the peritoneal cavity and cause tuberculous peritonitis.

Course of Primary Infection

  1. Healing – healing takes place with formation of a fibrous scar( fibrosis)
  2. Calcification and ossification
  3. Progressive primary tuberculosis – the primary focus grows and caseous material is disseminated through the bronchi to other  parts of the same lung or the opposite lung
  4. Miliary spread – bacilli enter the circulation via erosion in a blood vessel and spread to various fibres tissues and organs such as the liver, spleen, kidney, brain and bone marrow. This is called primary miliary tuberculosis.
  5. Pleural effusion – inflammatory reaction in the adjacent lung induces development of an effusion in the pleural cavity
  6. Tuberculous empyema – infection may involve the pleura directly from the Ghon’s focus and lead to development of the tubercuolus empyema.
  7. Reactivation of primary tuberculosis – lowered immunity and increased hypersensitivity of the host may result in activation of healed lesions resulting in progressive secondary tuberculosis. This situation is common in children.
  8. Mechanical effects – large granulomas can obstruct the bronchi leading to hypoxia and lung collapse (atelectasis)

 Secondary Infection

 Introduction

 Secondary pulmonary tuberculosis denotes active infection in a previously sensitized individual. It is also called secondary or post primary or re-infection or chronic tuberculosis and most cases represent reactivation of dormant bacilli from primary lesions. It occurs later in life as a reactivation or reinfection.

 Secondary tuberculosis is generally found in the apices of the lungs because of preference of M. tuberculosis for high oxygen tensions. Other sites and tissues include tonsils, pharynx, larynx, small intestine and the skin.

Secondary tuberculosis lesions may progress to cavity fibrocaseous tuberculosis, tuberculous bronchopneumonia or miliary tuberculosis.

 The infection may be acquired from endogenous or exogenous sources. The endogenous sources include reactivation of the dormant primary complex while the exogenous is fresh dose of re-infection by the tubercle bacilli.

 Secondary Pulmonary Tuberculosis

 Lesions in secondary pulmonary tuberculosis usually begin as 1 – 2 cm apical area of consolidation of the lung and with time develop a small area of central caseation necrosis and peripheral fibrosis.

 Secondary pulmonary tuberculosis occurs by haematogenous spread of infection from primary complex to apex of the affected lung where oxygen tension is high and favourable for growth of aerobic tubercle bacilli. HIV /AIDS patients previously exposed to tuberculous infection have a high incidence of reactivation of primary pulmonary tuberculosis with hilar lymph node involvement rather than cavitation and apical lesions in the lungs.  

 Course of Secondary Pulmonary Tuberculosis

 1.      Healing with fibrosis, scarring and calcification

2.      Lesions coalesce to form larger area of  tuberculous pneumonia producing progressive secondary pulmonary tuberculosis with pulmonary and extra-pulmonary involvement such as fibrocaseous tuberculosis, tuberculous caseous pneumonia and miliary tuberculosis

 Fibrocaseous Tuberculosis

 The area of tuberculous pneumonia undergoes massive central necrosis, which may break into a bronchus forming a cavity (cavity or open tuberculosis) or remain as a soft caseous lesion (non-cavity or chronic fibrocaseous tuberculosis).

 The cavity developed forms a favourable environment for proliferation of tubercle bacilli because of the high oxygen tension. The cavity may communicate with the bronchial tree and become the source of spread of the infection (open tuberculosis). Open cases of secondary tuberculosis may implant tuberculous lesions on mucosal linings of air passages resulting in endobronchial and endotracheal tuberculosis.  Ingestion of sputum containing tubercle bacilli produces laryngeal and intestinal tuberculosis.

 PATHOLOGY

 Macroscopy

  1. Cavity is spherical with thick fibrous wall lined by yellowish, caseous necrotic material
  2. Lumen has thrombosed blood vessels
  3. Areas of consolidation surround the lumen
  4. Thickened overlying pleura

 Microscopy

  1. Cavity has oesinophilic, granular, caseous material
  2. Dystrophic calcification
  3. Granulomas made of epitheloid cells
  4. Langhan’s giant cells
  5. Lymphocytes
  6. Central necrosis
  7. Fibrosis of the outer wall of the cavity

 Complications of Cavitations

  1. Aneurysm
  2. Haemoptysis (due to aneurysm)
  3. Bronchopleural fistula
  4. Tuberculous empyema
  5. Thickened pleura with adhesions

 Tuberculous Pneumonia

 Tuberculous pneumonia is an overwhelming infection characterized by extensive tuberculous consolidation of one or more lobes of the lungs. The tuberculous lesion in an individual spreads to the rest of the lung and produces extensive caseous pneumonia. Persons with AIDS and immunocompromised persons are prone to the rapidly progressive infection.

 Macroscopy

The lesions show exudative reaction with oedema, fibrin, polymorphs and monocytes.

Numerous tubercle bacilli in the exudates

 Miliary Tuberculosis

 Miliary tuberculosis develops if a mass of tuberculous inflammatory tissue erodes into a large blood vessel disseminating large numbers of the organisms throughout the body via the blood stream. The term miliary expresses the resemblance of the multiple foci of disseminated tubercles in the liver, spleen, kidney and other tissues to millet seeds.

 The spread is either by entry of infection into the pulmonary vein or pulmonary artery. Spread via the pulmonary vein produces dissemination or isolated organ lesions in different extra-pulmonary sites such as the liver, kidney, spleen, brain and bone marrow. Pulmonary artery dissemination restricts spread of miliary lesions within the lungs.   

 CLINICAL FEATURES

 Clinical features vary depending on the location, extent and type of tuberculous lesions. In a great majority of individuals, primary tuberculosis is symptomless. We shall discuss the secondary pulmonary tuberculosis

 Systemic

  1. Fever,
  2. Night sweats
  3. Fatigue
  4. Weight loss
  5. Loss of appetite
  6. Lymphadenopathy

 Lungs

  1. Productive cough
  2. Haemoptysis
  3. Pleural effusion
  4. Dyspnoea
  5. Orthopnoea
  6. Lung collapse
  7. Monophonic wheeze
  8. Bronchiectasis often in the middle lobe (Brock’s syndrome)
  9. Examination – IPPA

 INVESTIGATIONS AND DIAGNOSIS

  1. History and physical examination
  2. Imaging (Chest X-ray)
  3. Sputum examination
  4. Total blood counts
  5. Fibreoptic bronchoscopy
  6. Biopsies

COMPLICATIONS

  1. Pleurisy
  2. Pneumothorax
  3. Empyema or pyopneumothorax
  4. Tuberculous laryngitis
  5. Tuberculous enteritis
  6. Ischiorectal abscesses
  7. Blood borne dissemination
  8. Respiratory failure
  9. Cardiac failure

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Topic 4: PULMONARY VASCULAR DISEASE

INTRODUCTION

Diseases of the cardiovascular (heart) system affect the lungs and diseases of the lungs affect the heart due to the unique anatomical and functional characteristics of the pulmonary vasculature in which the pressure in the pulmonary arteries is much lower than that in the systemic arteries and that the pulmonary artery is thinner than the systemic arterial system.

The term acute lung injury refers to a number of pulmonary lesions affecting mainly the endothelium and epithelium caused by various factors and affecting the vascular components, which in turn affect the lungs causing injury.

Vascular and haemodynamic diseases of the lung include -

  1. Pulmonary oedema and congestion
  2. Pulmonary hypertension
  3. Pulmonary embolism and infarction
  4. Adult respiratory distress syndrome
  5. Pulmonary vasculitis
  6. Acute interstitial pneumonia

PULMONARY OEDEMA

 INTRODUCTION

 Pulmonary oedema is accumulation of fluid in the lung tissues (pulmonary interstitium) due to an increase fluid in the alveolar wall and if severe affects the alveolar spaces. The main cause is left ventricular failure, which results in increased pressure in the alveolar capillaries.

 Fluid leaks into the pulmonary interstitium causing increased flow of fluid into the pulmonary lymphatics resulting in stiffness of the lungs giving rise to a subjective sensation of dyspnoea. Rupture of the capillaries in the pulmonary system allows leakage of red cells into the interstitium and alveoli. The haemoglobin is phagocytosed by the macrophages, which accumulate the iron pigment and lie in the alveoli and interstitium as the “heart failure cells”.

CAUSES

1)      Haemodynamic disturbances (haemodynamic/cardiogenic oedema)     

a.       Increased hydrostatic pressure (increased pulmonary venous pressure)

Left heart (ventricular) failure – commonest

Volume overload

Pulmonary vein obstruction

b.      Reduced oncotic pressure – less common

Hypoalbuminaemia

Nephrotic syndrome

Liver disease 

Protein losing enteropathy

 c.       Lymphatic obstruction – rare

 2)      Oedema due to micro vascular injury (alveolar injury)

a.       Infections

Pneumonia

Septicaemia

b.      Inhaled gases

Oxygen

Smoke

c.       Liquid aspiration

Gastric contents

Near drowning

d.      Shock

e.       Trauma

f.        Radiation

g.      Transfusion related

 3)      Oedema due to undetermined origin

a.       High altitude

b.      Neutrogena (CNS trauma)

 PATHOGENESIS AND PATHOPHYSIOLOGY

 1)      Haemodynamic

 Increased hydrostatic pressure due to left sided heart failure and congestive cardiac failure results in increased escape of fluid into the lung interstitium. The fluid accumulates initially in the basal regions where the hydrostatic pressure is greater in this region (dependent oedema)

 2)      Microvascular Injury

 Injury to the capillaries of the alveolar septa result in increased permeability of the capillaries facilitating leakage of fluid and proteins into the interstitial spaces and alveolar (in severe situations)

PATHOLOGY

Macroscopy

  1. Wet heavy lungs
  2. Soggy lungs

Microscopy

  1. Engorged alveolar capillaries
  2. Alveolar microhaemorrhages
  3. Haemosiderin-laden macrophages (heart failure cells)
  4. Fibrosis and thickening of alveolar walls

 CLINICAL FEATURES

What are the clinical features?

INVESTIGATIONS

  1. What investigations will be relevant?
  2. What parameters will be significant in these investigations?

 COMPLICATIONS

Ø  Outline the complications stating their pathophysiology and differentiating factors

 PULMONARY HYPERTENSION

 INTRODUCTION

 Pulmonary hypertension (increased pulmonary arterial pressure) is a systolic blood pressure in the pulmonary arterial circulation of > 30 mmHg. The normal pressure in the pulmonary system is 30/15 mmHg and 3 – 8 mmHg in the arteries and veins respectively.

 The most important causes of pulmonary hypertension are COAD, fibrosis of the lungs and chronic pulmonary venous congestion. Pulmonary hypertension causes structural damage to the pulmonary vessels resulting in increased work on the right side of heart and right ventricular failure (Cor pulmonale) 

 CLASSIFICATION

 Can be classified as -

 1)      Primary

2)      Secondary

 PRIMARY (IDIOPATHIC)

 Introduction

 This is uncommon and the causes are unknown.

 Causes

 Suggested causes include – neurohormonal vasoconstrictor mechanism, unrecognized thrombo-embolism or amniotic fluid emboli during pregnancy, collagen vascular disease, veno-oclusive disease and familial occurrence.

 Pathogenesis

 Unknown

 SECONDARY

 This occurs secondary to a lesion recognized in the heart of lungs. It is more common.

 1)      Passive pulmonary hypertension

  1. Commonest
  2. Produced by lesions that increase pressure in the pulmonary veins (pulmonary venous congestion)
    • Mitral valve disease (mitral stenosis)
    • Chronic left ventricular failure – severe systemic hypertension, aortic stenosis and myocardial fibrosis 

 2)      Increased pulmonary blood flow  (hyperkinetic or reactive pulmonary hypertension)

Cardiac shunts – PDA, ASD and VSD

3)      Vaso-occlusive /Mechanical arterial obstruction

a.       Obstruction – block in pulmonary circulation

  1. Multiple emboli/thrombosis
  2. SCD
  3. Schistosomiasis
  4. Foreign body emboli (e.g. in drug addicts)

b.      Obliteration – reduced pulmonary vascular bed by chronic parenchymal lung disease (destruction of lung capillary bed)

  1. Chronic emphysema, Chronic bronchitis
  2. Bronchiectasis, Pulmonary tuberculosis
  3. Pneumoconiosis
  4. Interstitial fibrosis

 c.       Vasoconstrictive  - widespread sustained hypoxia results in vasoconstriction and alveolar  hyperventilation and pulmonary hypertension

  1. High altitude
  2. Pathologic Obesity (Pickwickian syndrome)
  3. Severe hyphoscoliosis
  4. Upper airway disease causing tonsilar hypertrophy

 4)      Idiopathic

PATHOLOGY

Heart

  1. Right ventricular hypertrophy
  2. Right atrial dilatation

Arteries and small pulmonary arteries

  1. Medial hypertrophy
  2. Thickening and reduplication of elastin

 Medium sized arteries

  1. Medial hypertrophy
  2. Intimal thickening
  3. Thickening of elastic
  4. Adventitial fibrosis

 Large arteries

Atheromatous deposits 

CLINICAL FEATURES

Ø  What investigations will be relevant?

Ø  What parameters will be significant in these investigations?

 INVESTIGATIONS

Ø  Outline the complications stating their pathophysiology and differentiating factors

 Adult Respiratory Distress Syndrome (Diffuse Alveolar Damage)

Adult respiratory distress syndrome is also called shock lung, acute alveolar injury, traumatic wet- lungs, post-traumatic insufficiency. ARDS is a syndrome caused by diffuse alveolar capillary damage characterized by rapid onset of severe life threatening respiratory insufficiency, cyanosis and severe arterial hypoxaemia resulting in multiple organ failure. It occurs as a complication of numerous diverse conditions due to injury to the lung and systemic disorders. 

CAUSES

1)      Infections

a.       Sepsis

b.      Diffuse pulmonary infections  - viral pneumonia, military tuberculosis, mycoplasma

c.       Gastric aspiration

2)      Physical injury

a.       Mechanical trauma – head injury

b.      Pulmonary contusions

c.       Near drowning

d.      Fractures with fat embolism

e.       Burns

f.        Ionizing radiations

3)      Inhaled irritants - Oxygen toxicity, Smoke, Metal fumes, War gases, Irritant gases and chemicals

4)      Chemical injuries – Heroin, ASA, Paraquat , Barbiturate overdose

5)      Haematological - Multiple transfusions , D.I.C

6)      Pancreatitis

7)      Uraemia

8)      Cardiopulmonary by-pass

9)      Hypersensitivity reactions

10)  Organic solvents

 PATHOGENESIS

Pathology of ARDS

PATHOLOGY

Injury results in increased vascular permeability (involving mainly type I alveolar) and necrosis that affects both capillary endothelium and alveolar epithelium resulting in intra-alveolar oedema, congestion, fibrin deposition and eventually HYALINE MEMBRANE.

Macroscopy

1)      Stiff, congested and heavy lungs

Microscopy

  1. Interstitial and intra-alveolar oedema
  2. Necrosis of alveolar epithelium
  3. Congestion and intra-alveolar haemorrhage
  4. Fibrosis
  5. Changes as those seen in bronchopneumonia 

CLINICAL FEATURES

  1. Profound dyspnoea
  2. Tachypnoea
  3. Cyanosis
  4. Hypoxaemia
  5. Respiratory distress

 INVESTIGATIONS

  1. Chest X-ray - diffuse bilateral infiltrates
  2. Lung volumes
  3. Blood counts

Ø  Outline the complications stating their pathophysiology and differentiating factors

 

COMPLICATIONS

Outline the complications 


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Topic 4: PULMONARY TUMORS

INTRODUCTION

Lung cancer (carcinoma of the bronchus) is most common cause of death in industrialized countries with a peak incidence of 40 – 70 years (50 – 60 years). A variety of benign and malignant tumours arise in the lungs with the majority (90 – 95%) being malignant. The tumours are largely due to carcinogenic effects of cigarette smoke and industrial carcinogens. The lung is the most common site of metastatic tumours through blood and lymphatic spread.

AETIOLOGY AND PREDISPOSING FACTORS

Is due to occupational and environmental factors

  1. Tobacco smoking
  2. Industrial hazards (Radiation/radioactive material , Asbestosis , Nickel , Chromium, Fe oxides, Coal gas plants , Uranium)
  3. Air pollution – atmospheric pollutants – petrochemical industries
  4. Genetic/familial
  5. Precursor lesions – squamous dysplasia and CIS, atypical adenomatous hyperplasia and diffuse idiopathic pulmonary hyperplasia
  6. Dietary factors – increased incidence in vitamin A deficiency
  7. Chronic scarring – due to chronic inflammatory changes ,old tuberculosis, asbestosis, chronic interstitial fibrosis and old infarcts  

CLASSIFICATION

 A.    PRIMARY TUMOURS

 1)      Epithelial Tumours

a.     Benign tumours – Papilloma, Adenoma

b.    Malignant tumours

                                  i.     Bronchogenic carcinoma - Squamous cells carcinoma (SCC), Adenocarcinoma, Small cell carcinoma , Large cell carcinoma

Adenosquamous carcinoma

                              ii.      Others - Carcinoid tumours , Bronchial gland carcinomas

 2)      Soft Tissue Tumours

a.       Fibroma and Fibrosarcoma

b.      Lipoma

c.       Haemangioma

d.      Lymphangioma

 3)      Pleural Tumours

  1. Benign mesothelioma
  2. Malignant  mesothelioma

 4)      Miscellaneous

a.       Pulmonary blastoma

b.      Malignant melanoma

c.       Malignant lymphoma

 B.     SECONDARY TUMOURS

  1. Kidney
  2. Breast
  3. Testis
  4. G.I.T/bowel
  5. Thyroid
  6. Pancreas 

 C.    TUMOUR LIKE LESSIONS

  1. Harmatomas
  2. Eosinophilic granuloma
  3. Inflammatory pseudotumours

 PATHOLOGY

 The tumour arises from the main bronchus or their large branches (central tumour) or the periphery of the lungs (peripheral tumour)

Macroscopy

  1. Warty mass/irregular
  2. Cauliflower
  3. Mass
  4. Ulcer

Microscopy

What microscopic picture do you expect?

 SPREAD

 1)      Local spread

    1. Through the wall into the surrounding lung tissues and pleural cavity
    2. Peribronchial spread
    3. Direct extension into the pleura and adjacent mediastinal structures  affecting structures such as the superior vena cava (brings about venous congestion in the neck) and nerves – recurrent laryngeal (vocal cord paralysis) and phrenic (paralysis of the diaphragm)
    4. Spread to involve the brachial plexus (produces motor symptoms) and cervical sympathetic chain (produces Horner’s syndrome – Ptosis (drooping eyelid), Enopthalmos (sunken eye), Miosis (small pupil) and Anhydrosis (loss of sweating)

2)      Lymphatic

    1. Ipsilateral and contraleteral hilar and peribronchial lymph nodes 
    2. Metastasis – mediastinal, cervical, supraclavicular, paraortic
    3. Retrograde spread to the abdomen

 3)      Transcoelomic

Spread within the pleural cavity resulting in malignant pleural effusion

 4)      Haematogenous – very common due to invasion of pulmonary veins

 Spreads to the brain, bone (ribs, vertebrae, humeri, femora – pathological fractures), liver, adrenal glands

CLINICAL FEATURES

Clinical features are variable and result from local effects, effects of bronchial obstruction, local and distant metastasis and paraneoplastic effects.

1)      General constitutional

  1. Fever
  2. Weight loss
  3. Anaemia
  4. Jaundice

2)      Local symptoms

  1. Cough
  2. Chest pain
  3. Dyspnoea
  4. Haemoptysis

 Causes of Haemoptysis

 a)      Inflammatory

  1. Bronchiectasis
  2. Bronchitis
  3. Tuberculosis
  4. Lung abscess
  5. Pneumoconiosis

 b)      Neoplastic

  1. Primary and metastatic lung cancer
  2. Bronchial adenoma

 c)      Others

  1. Pulmonary thromboembolism
  2. LVF
  3. Mitral stenosis
  4. Primary pulmonary hypertension
  5. Foreign body
  6. Trauma
  7. Haemorrhagic diathesis

 3)      Bronchial obstruction symptoms

  1. Bronchopneumonia
  2. Lung abscess
  3. Bronchiectasis
  4. Pleural effusion
  5. Productive cough

 4)      Symptoms due to metastasis

  1. Superior vena cava syndrome
  2. Painful bony lesions
  3. Pathological fractures
  4. Paralysis of recurrent laryngeal nerve
  5. Neurologic manifestations
  6. Hepatomegally

 5)      Paraneoplastic – ectopic hormone production

  1. ACTH  adrenal hyperplasia  increased blood cortisol  Cushing syndrome
  2. ADH  water retention  dilutional hyponatraemia
  3. Parathyroid hormone  hypercalcaemia
  4. Calcitonin  hypocalcaemia
  5. Gonadotropins  gynaecomastia

 6)      Other systemic manifestations

  1. Neuromuscular - Myopathy , Peripheral neuropathy
  2. Skeletal - Digital Clubbing, Hypertrophic osteodystrophy
  3. Cutaneous - Acanthosis nigrans
  4. Cardiovascular - Migratory thrombophlebitis  (Trousseaus syndrome)
  5. Haematologic - Abnormalities in coagulation 


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Topic 4: PULMONARY TUMORS (Cont')

COMMON HISTOLOGICAL TYPES OF BRONCHOGENIC CARCINOMA

1)      Squamous cell carcinoma

  1. Most common bronchogenic carcinoma
  2. Derived from metaplastic squamous epithelium
  3. M > F
  4. Strong association with cigarette smoking
  5. Arise in central bronchus (central)
  6. Causes bronchial obstruction
  7. Exhibits rapid spread 

2)      Adenocarcinoma

  1. F > M (commonest bronchogenic carcinoma in women)
  2. Develops as a peripheral tumours (may occur centrally)
  3. Slow growing
  4. Associated with areas of chronic scarring
  5. Weak association with cigarette smoking 
  6. 4 main types – acinar (gland like) occurring in large bronchi, papillary (frond of tumour on thin septa) in the lung periphery, bronchoalveolar (papillary,  cuboidal tall columnar and mucous secreting epithelium) and solid carcinoma (poorly differentiated, lacks acinar, tubes or papillae)

 3)      Small cell carcinoma

  1. Most aggressive and highly malignant tumour arising from the bronchial epithelium
  2. Exhibits rapid growth rate
  3. Early and wide metastasis
  4. Frequently originates in hilar and central
  5. Strong association with smoking
  6. Most associated with ectopic hormone secretions
  7. ü Cell nuclei resemble an aot hence the name oat cells carcinoma

 4)      Large cell carcinoma

  1. Highly malignant poorly differentiated central or peripheral tumour
  2. M > F
  3. Strong association with smoking
  4. Large nuclei, prominent nucleoli, abundant cytoplasm with well-defined boarders
  5. Widely disseminated with poor prognosis

 DIAGNOSIS AND INVESTIGATIONS

 1)      History

2)      High index of suspicion

3)      Physical examination

4)      Investigations

  1. Chest X-ray
  2. Sputum examination
  3. Pleural effusion tap – analysis
  4. Bronchoscopy and biopsy
  5. Blood counts
  6. Liver function tests
  7. Renal function tests

What are the complications of tumours of the lungs?

COMPLICATIONS

STAGING

TNM

Feature

Characteristics

T1

Tumour < 3 cm without pleural or main stem bronchus involvement

T2

Tumour > 3 cm or involvement of main stem bronchus 2 cm from carina, visceral pleural involvement or lobar atelectasis

T3

Tumour with involvement of chest wall (including superior sulcus tumours), diaphragm, mediastinal pleura, pericardium, main stem bronchus 2 cm from carina or entire lung atelectasis 

T4

Tumour with invasion of mediastinum, heart, great vessels, trachea, oesophagus, vertebrae=l body or carina or with a malignant pleural effusion

N0

No demonstrable metastasis to regional lymph nodes

N1

Ipsilateral hilar or peribronchial nodal involvement

N2

Metastasis to ipsilateral mediastinal or subcarinal lymph nodes

N3

Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or contarlateral scalenae or supraclaviclar lymph nodes

M0

No (known) distant metastasis

M1

Distant metastasis

 

 

Stage

Stage Grouping

T

N

M

Ia

T1

N0

M0

Ib

T2

N0

M0

IIa

T1

N1

M0

IIb

T2

N1

M0

T3

N0

M0

IIIa

T-3

N2

M0

T3

N1

M0

IIIb

Any T

N3

M0

T3

N2

M0

T4

Any N

M0

IV

Any T

Any N

M1

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Topic 4: DISORDERS OF PLEURA

 

The two layers of the pleura (visceral and parietal) enclose the pleural cavity containing < 15 mls of clear serous fluid.  The visceral pleura covers the lungs. The pleura is lined by a single layer of flattened mesothelial cells and there is a thin layer of connective tissue underneath.

Fluid is formed under the influence of hydrostatic pressure and osmotic pressures and changes in the permeability of the local vessels and there is constant generation of fluid by the parietal pleura and reabsorption by the visceral pleura surface.

Majority of pleural disorders occur as a complication of other diseases. The most important primary diseases of the pleura are primary intrapleural bacterial infections and primary neoplasms of the pleura.

Diseases of the pleura include -

  1. Inflammations (Pleurisy)
  2. Pleural Effusion
  3. Pneumothorax
  4. Haemothorax
  5. Tumours 

FLUID IN THE PLEURA

Several fluid types can accumulate in the pleural space and if in large amounts result in compression of the lung. These include -

  1. Pus - Empyema due to infection
  2. Blood - Haemothorax due to trauma or surgery
  3. Chyle - Chylothorax due to leakage from the thoracic duct
  4. Fluid effusion (transudate and exudates)
    1. Transudate – low protein fluid due to movement of excess fluid through normal vessel walls as a result of increased hydrostatic pressure as seen in cardiac failure
    2. Exudates -       high protein fluid (with fibrinogen/fibrin) due to movement of fluid through damaged vessel walls commonly due to infarctions, infection or tumours

NOTE: There could be accumulation of air (pneumothorax)

PLEURAL EFFUSION

Pleural effusion is accumulation of fluid in the pleural space. It is a common manifestation of primary and secondary pleural disease. Pleural effusion is a common complication of malignant disease such as breast and lung cancer, lymphoma and other malignancies. 30% of the cases of pleural effusion are secondary to malignant diseases.

 NORMAL PLEURAL PHYSIOLOGY

 The layer between parietal and visceral is a potential spaced (5 mls). The mechanism of fluid production and reabsorption depends on the; -

  1. Capillary permeability
  2. Hydrostatic pressure
  3. Colloid osmotic pressure
  4. Lymphatic drainage

 Parietal pleural transudate 

 In production and absorption of pleural effusion, protein free fluid filters from the systemic capillaries in the parietal pleura into the pleural space and then into the pulmonary capillaries of the visceral pleura largely due to the net result of hydrostatic and osmotic pressures. Lymphatic circulation accounts for reabsorption of 10% of the pleural fluid (important in keeping pleural space protein free). Increase in proteins in the pleural fluid will increase the osmotic pressure resulting in formation of exudates.

PLEURAL EFFUSION – MECHANISM

Pleural effusions develop when normal equilibrium between the four factors affecting pleural fluid physiology is disturbed. Mechanisms producing protein rich effusions in malignant disease involve increased rate of production and/or reduced absorption of pleural fluid.

Pleural tumour may cause capillary damage or may irritate the pleura producing inflammation with the changes resulting in increased permeability and passage of protein molecules and fluid into the pleural space. Tumour spread may cause lymphatic obstruction resulting in reduced absorption of protein-rich pleural fluid. Lymphatic obstruction involving the mediastinal lymph nodes may cause obstruction of the superior vena cava and pericardial invasion resulting in increased systemic and/or pulmonary venous pressure.

Mechanism of Pleural Effusion

Pleural effusion develops because of the following mechanisms

  1. Increased hydrostatic pressure as in congestive cardiac failure
  2. Increased vascular permeability – as in pneumonia
  3. Decreased osmotic/oncotic pressure – as in nephrotic syndrome
  4. Increased intrapleural negative pressure – as in etelectasis
  5. Reduced lymphatic drainiage – as in mediastinal carcinomatosis 

CAUSES OF PLEURAL EFFUSION

TRANSUDATES

Transudates have protein content less than 30 gm per litre and lactic hydrogenese less than 200 i.u per litre. This occur because of reduced osmotic pressure or increased hydrostatic pressure or both.

Causes:

  1. Cardiac Failure
  2. Nephrotic Syndrome
  3. Constrictive pericarditis
  4. Hypothyroidism
  5. Meig’s syndrome (Ovarian tumour producing right-sided pleural effusion)
  6. Cirrhosis
  7. Peritoneal dialysis

EXUDATES

 Exudates have protein content more than 30 gm per litre and lactic hydrogenase more than 200 i.u per litre

 Causes

 1)      Infections

  1. Bacterial infections e.g. pneumonia (Streptococcus pneumoniae, Haemophilus, Klebsiella, Pseudomonas, Bacteroiods)
  2. Tuberculosis
  3. Fungal infections
  4. Viral infections
  5. Parasitic infections

2)      Neoplastic

  1. Metastatic tumours – breast, lungs, lymphoma, ovary, genito-urinary, G.I.T, and melanoma
  2. Mesothelioma (primary tumours)

3)      Pulmonary infarction – thromboembolic disease

 4)      GIT Diseases

    1. Eosophageal perforation
    2. Pancreatic disease
    3. Intra-abdominal abscess
    4. Diaphragmatic hernia
    5. After liver transplant
    6. Subphrenic abscess

5)      Collagen-vascular disease - Rheumatoid pleuritis, S.L.E.

6)      Iatrogenic injury

7)      Drug induced pleural disease – Nitrofurantoin, Bromocriptine

8)      Ovarian hyperstimulation syndrome

9)      Pericardial disease

10)  Radiation therapy

 INFLAMMATORY PLEURAL EFFUSION 

 Introduction

 Inflammation of the pleura results in pleutitis or pleurisy whose effects depend on the characters of the exudates which can be serous, fibrinous, serofibrinous, suppurative/empyema and haemorrhagic

 Causes

 a)      Infection

  1. Usually due to spread from pneumonia and tuberculosis
  2. Following penetrating chest injury e.g. stab wounds

 b)      Auto-immune

    1. Rheumatoid arthritis
    2. S.L.E

 c)      Overlying a pulmonary infarct

 Serous, Fibrinous and Serofibrinous Pleurisy

 This is seen in acute inflammation, which produces exudates. It arises from an infection in the lungs (tuberculosis, pneumonia, pulmonary infarcts, lung abscess and bronchiectasis), collagen disease (rheumatoid arthritis and S.L.E), uraemia, metastatic involvement of the pleura, irradiation of the lungs tumours, systemic infectiosn (typhoid fever).

 This produces chest pain on breathing and a pleural rub due to inflammatory fibrnous exudate. A minimal exudate will be reabsorbed resulting in resolution. Repeated attacks will result in organization forming fibrous adhesions and obliteration of the pleural cavity.

 Suppuration (Empyema Thoracis)

 This purulent pleural exudate results from bacterial and mycotic seeding of the pleural space. Serofibrinous exudate can be converted to suppurative.

 Causes

  1. Direct spread of phonemic infection from the lung
  2. Direct extension of from subdiaphragmatic or liver abscess
  3. Penetrating chest injuries to chest wall
  4. Lymphatic
  5. Haematogenous

 Features

  1. Loculated yellowish-green creamy pus (large volumes)
  2. Empyema eventually replaced by granulation tissue and fibrous tissues 

 Haemorrhagic Pleurisy

 Haemorrhagic pleurisy is characterized by sanguineous inflammatory exudate having inflammatory cells or exfoliated tumour cells.

 Causes

  1. Metastasis (neoplastic)
  2. Bleeding disorders (diathesis)
  3. Rickettsial

 NON- INFLAMMATORY PLEURAL EFFUSION 

 Includes fluid collections in the pleural cavity such as: - hydrothorax, haemothorax and chylothorax.

 Hydrothorax

 Hydrothorax is accumulation of clear, straw-coloured transduate fluid within the pleural cavities. May be limited to part of a pleural cavity by pre-existing pleural adhesions.

 Causes

 1)     CCF

2)     Renal failure

3)     Liver cirrhosis

4)     Meig’s syndrome

5)     Pulmonary oedema

6)     Primary and secondary tumours

Investigations

Chest X-ray

  1. Obliterated costodiaphragmatic angle
  2. Opacities
  3. Tracheal deviation (opposite side)

Haemothorax

 Escape and accumulation of pure blood in the pleural cavity. It may occur as a fatal complication of ruptured aortic aneurysm, trauma to the chest wall and thoracic viscera. If blood is not removed, it becomes organized forming fibrous adhesions resulting in fibrosis and obliteration of the pleural cavity.

 Chylothorax

 This is accumulation of milky fluid of lymphatic origin. It is white due to the presence of fatty acids. It may occur because of thoracic duct trauma or obstruction.

 CLINICAL FEATURES OF PLEURAL EFFUSION 

 The clinical features depend on the rate of accumulation of fluid and its size.

 Symptoms

  1. May be silent
  2. Shortness of breath
  3. Unproductive cough
  4. ± chest pain (often pleuritic)

 Signs

 1)     Signs of pleural effusion

  1. chest movement
  2. chest expansion
  3. Deviated trachea
  4. Breath sounds
  5. Aegophony
  6. Stony dull percussion

 2)     Features of respiratory distress

DIAGNOSIS OF PLEURAL EFFUSION 

Procedure

Features

History

Ø  Shortness of breath

Ø  Pleuritic chest pain

Ø  Unproductive cough

Examination

Ø  ¯ chest movement, ¯ chest expansion

Ø  Deviated trachea, ¯ breath sounds

Ø  Aegophony

Ø  Stony dull percussion

Radiology

Ø  Chest X-ray, Ultrasound

Ø  CT scan

Pleural aspiration

Ø  Gross appearance

Ø  Biochemistry

Ø  Cytology, Microbiology

Pleural biopsy

Ø  Histology

Thoracoscopy

Ø  Gross appearance, Pleural fluid, cytology

Ø  Pleural biopsy

 

INVESTIGATIONS 

1)     Radiology

  1. Chest X-ray – erect – demonstrate pleural effusion, blunting of the costophrenic angle
  2. Ultrasound – distinguishes between pleural thickening and fluid
  3. CT scan – reveals an underlying malignancy

2)     Pleural effusion aspiration

  1. Gross appearance
  2. Biochemistry
  3. Cytology
  4. Microbiology
  5. Histology

3)     Blood counts

4)     Thoracoscopy


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Topic 4: PLEURA -Cont' (THORACIC TRAUMA)

 

Thoracic trauma is an emergency resulting in consequences of hypoxia to the brain and heart, which are rapidly fatal. Such patients often have multiple injuries. The injuries are either blunt or penetrating injuries. Consequences of injury of the thoracic viscera (heart and lungs) are more important and life threatening than injuries of the thoracic skeleton. Hypotension and hypoxia due to cardiorespiratory failure are rapidly fatal.

Blunt Thoracic Trauma

  1. Fracture ribs
  2. Peumothorax
  3. Haemothorax
  4. Sternal fractures
  5.  Diaphragm
  6. Lungs
  7. Mediastinum
  8. Heart

Penetrating Thoracic Trauma

  1. Wounds
  2. Viscera
    1. Lungs
    2. Heart
    3. Oesophagus
    4. Thoraco-abdominal 

BLUNT INJURIES

Fracture Ribs

Fractures of the ribs many be single or multiple usually following severe trauma. May be associated with aortic rupture. It may also result in a flail chest in which fractures of several ribs in two places or a combination of fracture of the ribs and sternum. Paradoxical movement of the flail segments of 12 sqm or more results in respiratory embarrassment. Small areas of flail chest will produce symptoms in older persons with existing respiratory disorder or pathology.

Reduced arterial oxygenation occurs due to pulmonary contusion, pneumonia, respiratory failure and ARDS. Patients with large, free segments, pre-existing respiratory disease or those who develop infection with have poor function.

Haemothorax

Haemothorax is accumulation of pure blood in the pleural cavity. It results from trauma to the chest wall or to the thoracic viscera and rupture of aortic aneurysm. Blood should be removed from the pleural cavity as early as possible otherwise blood will organize to form fibrous adhesions resulting in obliteration of the pleural cavity (fibrothorax).

Sternal Fractures

They are less common and indicate great force applied to the chest wall. Diagnosis is made through palpation and chest radiographs.

Diaphragm

The right hemidiaphragm is well protected by the liver than the left one, which is prone to injury. It usually follows blunt injury and sudden explosive increase in pleuroperitoneal pressure gradient.

Lungs

Deceleration produces differentiated forces across the alveolar capillary membrane producing rupture, which leads to alveolar haemorrhage and oedema. Coexistence shock and pulmonary under perfusion and pulmonary neutrophils sequestration worsening the situation.

Mediastinum

Severe deceleration results in rupture of mediastinal vessels.

Heart

Contusion of the heart may occur with blunt injuries.

PENETRATING INJURIES

Wounds

Skin wound of stab wound is small and clean. High velocity missiles cause a larger exit than entry wounds. Extensive tissue destruction results in delayed primary closure. 

Viscera

1)     Lungs

Ø  Laceration results in haemopneumothorax

2)     Heart

Ø  Penetration of the heart results in cardiac tamponade and precardial wounds

3)     Oesophagus

Ø  Uncommon

Ø  Results in pneumomediastinum, mediastinitis and left hydrothorax

4)     Thoraco-abdominal injuries occur due to: -

Ø  Penetrating would below 4th ICS anteriorly, sixth ICS laterally and eight ICS posteriorly

Ø  Penetration by a missile (bullet wounds)

Pneumothorax

INTRODUCTION  

Pneumothorax is accumulation of air in the pleural cavity. It can be – spontaneous (primary and secondary), traumatic and iatrogenic (therapeutic)

CAUSES

1)     Spontaneous pneumothorax

a.       Primary spontaneous pneumothorax

Ø  Occurs in thin young men due to rupture of congenital sub-pleural apical bleb

b.      Secondary spontaneous pneumothorax

  1. Rupture of emphysematous bulla
  2. Asthma
  3. Rupture of congenital cysts
  4. Pleural malignancy
  5. Cystic fibrosis
  6. Pneumonia
  7. Sarcoidosis
  8. Whooping cough
  9. Tuberculosis
  10. Chronic bronchitis in old patients
  11. Pulmonary infarction
  12. Bronchial cancer

2)     Traumatic pneumothorax

  1. Penetrating chest wounds
  2. Fracture of the ribs
  3. Oesophageal rupture

 3)     Iatrogenic (therapeutic) pneumothorax

  1. Subclavian cannulation
  2. Positive pressure artificial ventilation
  3. Pleural aspiration
  4. Oesophageal rupture during endoscopy
  5. Lung biopsy

 Tension Pneumothorax

 The defect in the lungs may act as a flap-valve and allows entry of air during inspiration but does not permit its escape during expiration resulting in tension pneumothorax. This requires urgent relieve.

EFFECTS

Depends on amount of air collected in the pleural cavity

  1. Small – it is reabsorbed
  2. Large – Dyspnoea, Chest pain , Lung collapse – pulls mediastinum to the unaffected side 
  3. Examination

Identify the Safety Triangle

What investigations will be relevant investigations?

INVESTIGATIONS

Identify thr relevant investigations.

What complications will be seen in such cases?

Tumours of the Pleura

 INTRODUCTION  

 Pleural tumours can be primary or secondary. Secondary metastatic tumours are more common with their primary sites being the lungs and the breast, others include ovarian and G.I.T tumours.

 BENIGN (SOLITARY) MESOTHELIOMA

 This is also called fibroma (fibrous tumour) and it is attached to the pleura by a pedicle.

 Macroscopy

  1. Small – enormous size
  2. Solitary
  3. Circumscribed firm mass
  4. Dense fibrous mass with occasional cysts filled with viscid fluid

 Microscopy

  1. Whorls of reticula and collagen fibres
  2. Rarely malignant

 MALIGNANT (DIFFUSE) MESOTHELIOMA

  1. Arise from visceral or parietal pleura
  2. Rare
  3. Highly malignant
  4. Associated with exposure to asbestosis
  5. Also arise in the peritoneum, pericardium, tunica vaginalis and genital tract

 Gross 

  1. Diffuse
  2. Thick
  3. White fleshy coating over parietal and visceral layers

 Microscopy

  1. Malignant mesothelioma
  2. Features of malignant cells

 Clinical Features

  1. Chest pain
  2. Dyspnoea
  3. Pleural effusion
  4. Infections
  5. Tumour effects

 Spread

 1)     Locally

Ø  Direct to the lungs

Ø  By lymphatics to the hilar and mediastinal lymph nodes

 2)     Distant metastasis -  to the liver 

What investigations will be relevant investigations?

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Topic 4: Summary

In this topic we have covered;
  1. Pneumonias.
  2. Tuberculosis.
  3. Acute respiratory distress syndrome.
  4. Pulmonary tumors.
  5. Pleural effusion.
  6. Thoracic trauma.
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Topic 4: References

  1. Kishasha M (2016). Textbook of human pathology. 1st edition, Acrodile publishers, Nairobi, Kenya.
  2. Harsh M (2014). Textbook of Pathology. 1st edition. New Delhi: Jaypee Brothers, Medical Pub, India
  3. Ngton C, & Muir (2014). Textbook of Pathology. 15th edition, New Delhi. Jaypee Brothers, India
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