CMS 251

CLINICAL PATHOLOGY
MODULE 1 CLINICAL PATHOLOGY I
By

NYAGA JOSPHAT MUTUNGI,

Senior Lecturer

Sept/October/NOVEMBER 2018, 2017/2018 ACADEMIC YEAR

Unit 2: The Respiratory System

UNIT OBJECTIVES

1. Describe congenital anomalies of the respiratory tract

2. Describe the aetiology, pathophysiology, pathology, features and complications of disorders of
the respiratory system
3. Explain the investigations in respiratory disorders

UNIT OUTLINE

1. Introduction and Paediatric Lung Diseases

2. Disorders of Upper Respiratory Tract
3. Respiratory Failure
4. Lung Collapse (Atelectasis)
5. Obstructive Lung Disease
6. Restrictive Lung Disease
7. Pulmonary Infections
8. Pulmonary Vascular Disease and Acute Lung Disease
9. Tumours of the Lungs
10. Disorders of the Pleura and Mediastinum

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Lesson 1: Introduction and Paediatric Lung Diseases

Learning Outcomes

At the end of the lesson, the leaner should be able to -

1. Briefly describe the anatomy of the respiratory tract

2. Outline the functions of organs of the respiratory tract
3. Outline conditions and diseases that affect the respiratory system
4. Discuss the developmental anomalies of the respiratory system
5. Describe the causes and effects of acute respiratory distress syndrome (hyaline
membrane disease)

General Introduction

1.0 INTRODUCTION

Respiration is the process by which O 2 is transported to and used by cells, and

CO2produced is eliminatedfrom 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 CO2is calledexternal 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 O 2for survival and to carry out their
functions. During their normal processes of work the cells use up O 2 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.

2.0 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

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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.

3.0 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

a. Nose
b. Pharynx
c. Nasopharynx,
d. Oropharynx
e. Laryngopharynx
f. Larynx
g. Trachea

2) Lower Respiratory Tract

a. Bronchial tree
b. Lungs

Diagram 1.1: Parts of Respiratory System

4.0 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

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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.

5.0 FUNCTIONS

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
a. Endothelial cells of the pulmonary capillaries secrete angiotensin converting
enzyme (ACE) which activates angiotensin I into angiotensin II
b. Lung tissues synthesize prostaglandins, acetylcholine, bradykinin and serotonin

6.0 INTRODUCTION 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 lungsallows 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.

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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.

7.0 CONDITIONS OF RESPIRATORY SYSTEM

1. Congenital Disorders
2. Paediatric lung disease - Hyaline membrane diseases (RDS)
3. The Upper Respiratory Tract
a. Inflammatory conditions - Coryza, Rhinitis, Sinusitis, Pharyngitis , Laryngitis,
Epistaxis
b. 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
a. Pneumonias
1. Bacterial (Lobar pneumonia, Bronchopneumonia, Staphylococcal pneumonia,
Klebsiella pneumonia)
2. Viral
3. Mycoplasmal
4. PCP
5. Atypical
6. Aspiration
7. Hypostatic
b. Fungal infections
c. Lung abscess
d. Empyema
e. Pulmonary tuberculosis
f. Pulmonary infections in HIV/AIDS
8. Restrictive Pulmonary Disease
a. Immunological pulmonary disease - Bronchial asthma, Allergic pneumonitis and
Good Pasture’s Syndrome
b. Pneumoconiosis
c. Collagen – Vascular disease
d. Pulmonary Fibrosis
9. Pulmonary vascular disease
a. ARDS
b. Pulmonary hypertension
c. Pulmonary oedema
10. Acute Lung Injury
11. Drug and toxin injury of the lungs
12. Tumours
13. Pleura
a. Pleural effusion
b. Pneumothorax
c. Tumours

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PAEDIATRIC LUNG DISEASE

Developmental Abnormalities

Developmental defects of the lungs include agenesis or hypoplasia of both lungs, one lung
or single lobe; tracheal and bronchial anomalies – atresia, stenosis and tracheobronchial
fistula; vascular anomalies; congenital lobar over-inflation (emphysema),
broncogeniccysts ; congenital airway malformation and pulmonary sequestrations

1.0 PULMONARY HYPOPLASIA

 Incomplete development of both lungs resulting in reduced weight, volume and acini
compared to body weight and gestational age
 Lung smaller than normal
 Incidence 10%
 Associated with other congenital abnormalities and lung compression by abnormal
masses and oligohydramnious
 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.

2.0 BRONCHIAL ATRESIA

 Results in severe narrowing of the bronchus

3.0 BRONCHOGENIC SEQUESTRATION

 Cysts attached to the trachea

 Represent accessory bronchial buds

4.0 BRONCHOPULMONARY SEQUESTRATION

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

Neonatal Respiratory Distress Syndrome (Hyaline

Membrane Disease)

Introduction

 Due to deficiency of surfactant (

 Primarily disease of premature infants
 Seen in infants of diabetic mothers (excess insulin production by the foetus suppresses
surfactant production)

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 Gestation 32 – 36 weeks 20% mortality
 < 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
constrictionresulting 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.

Diagram1.2: Pathogenesis of ARDS

RISK FACTORS

Pathology

The lungs: -

1. Have fibrous obliteration of bronchioles

2. Peribronchial fibrosis
3. Overdistended alveolar

Clinical Features

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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:

 Breathes faster than 60 breaths a minute

 Makes a grunting sound when he breathes out
 Has respiratory distress (what are the features)
 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 andoxygen toxicity to alveolar
lining cells)

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Lesson 2: Upper Respiratory Tract Disorders

Learning Outcomes

At the end of the lesson, the leaner should be able to -

1. Discuss conditions affecting organs of the upper respiratory tract

A. 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
a. Idiopathic (85%)
b. Trauma – nose pricking, fractures
c. Inflammation – rhinitis, sinusitis
d. Iatrogenic – nasal sprays, surgery
e. Hereditary – Hereditary haemorrhagic telangiectasis
f. Neoplasms – carcinoma, juvenile angiofibroma
2. Systemic
a. Anticoagulants – warfarin, NSAIDS
b. Hypertension
c. Blood dyscrasias – leukaemia
d. Hereditary coagulopathies – haemophilia

B. 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

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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.

Acute Rhinitis

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

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.

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.

3. 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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C. THE PHARYNX

1. Acute Nasopharyngitis

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

The histopathologyincludes -

 Hyperaemia
 Oedema
 Hyperactive mucosal glands
 Increased mucosal secretions
 Neutrophil polymorphs – usually sparse in viral infections but increase with secondary
bacterial infections
 Superficial destruction of ciliated epithelium
 Swollen/enlarged/distended mucosal glands

2. 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.

D. THE LARYNX AND TRACHEA

1. Acute Laryngitis and Tracheaitis

Acute laryngitis and tracheaitis are common occurrences

Aetiology

1. Viral
a. Adeno virus
b. Epstein Barr virus (EBV)

2. Bacteria
a. Strep. pneumoniae
b. Strep. pyogenes
c. Neisseria catarrhalis
d. Heamophilusinfluenzae
e. Corynebacteriumdiptheriae

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

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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?

E. 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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Lesson 3: Respiratory Failure & Atelectasis(Lung
Collapse)
Learning Outcomes
At the end of the lesson, the learner should be able to -
1. Discuss the causes and effects of respiratory failure
2. Discuss the pathophysiology of respiratory failure
3. Investigate a patient with respiratory failure
4. Describe the causes of lung collapse
5. Discuss the effects and features of lung collapse
6. Define lung collapse/atelectasis
7. Describe causes and effects of lung collapse
8. Discuss the pathophysiology and complications of lung collapse
9. Investigate a patient with lung collapse

Respiratory Failure

1.0 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 PaCO 2 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. PaO 2< 8.0 kPa (60
mmHg) or PaCO2> 7 kPa (55 mmHg).

2.0 MECHANISMS OF ARTERIAL HYPOXAEMIA

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

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

3.0 CAUSES

1. Extrinsic Lung Disorders

a. Respiratory centre depression
i. Drug overdose (sedatives, narcotics)
ii. Cerebral trauma or infarction
iii. Bulbar poliomyelitis

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 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

4.0 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

5.0 CLASSIFICATION

1. Type I – “Acute hypoxaemic” respiratory failure

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2. Type II – “Ventilatory failure” respiratory failure

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6.0 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 – Fibrosingalveolitis, Sarcoidosis, allergic alveolitis, asbestosis

Diagnosis

1. Arterial blood gases analysis – reduced PaCO2

2. Respiratory function tests – reduced FEVR and FEV1

7.0 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. GulleinBarre 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.

8.0 EFFECTS ON CVS

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

Pulmonary Hypertension

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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.

9.0 FEATURES OF RESPIRATORY FAILURE

 Tachycardia
 Tachypnoea
 Sweating
 Use of accessory muscles of respiration
 Pulsusparadoxical
 Inability to speak
 Paradoxical respiration (abdominal and thoracic components move in opposite
directions)
 Asynchronous respiration (discrepancy in the rate of movement of the abdominal and
thoracic components)
 Respiratory alternans
TASK
1. Explain the pathophysiology of the features above.
2. What investigations will be useful in a patient with respiratory failure?
3. Regarding the investigations in (2) above, state the important clinical parameters that will
be useful in making the diagnosis.

Collapse of Lung Tissue – Atelectasis

1.0 INTRODUCTION

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).

2.0 ATELECTASIS (Neonatal)

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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

3.0 ACQUIRED LUNG COLLAPSE

Can occur becauseofresorption atelectasis, compression atelectasis and contraction

atelectasis

Diagram 3.1: 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 [Link] then replace the air and oedema

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fluid, which become infected quite easily resulting suppuration and tissue destruction that
results in irreversible pulmonary fibrosis.

Diagram 3.2: 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
Diagram 3.3: Compression Atelectasis

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

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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

Contraction Atelectasis

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

Diagram 3.4: 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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Lesson 4: Bronchial Obstruction and Emphysema

Learning Outcomes

At the end of the lesson, the learner should be able to -

1. Describe causes and effects of bronchial obstruction

2. Describe causes and effects of emphysema
3. Diagnose bronchial obstruction and emphysema
4. Describe causes and effects of bronchiectasis
5. Diagnose bronchial obstruction, emphysema and bronchiectasis

Introduction - Obstructive Pulmonary Diseases

1.0 INTRODUCTION

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).

Table 1: Disorders of Airflow Obstruction

Clinical Term Anatomic Major Pathologic Aetiology Signs/symptoms
site changes
Chronic Bronchus Mucous gland Tobacco smoke Cough and sputum
Bronchitis hyperplasia and and pollutants production
hypersecretion
Bronchiectasis Bronchus Airway dilatation Persistent or Cough, purulent
and scarring severe sputum and fever
infections
Asthma Bronchus Smooth muscle Immunologic Episodic
hyperplasia, or undefined wheezing, cough
excess mucous causes and dyspnoea
and inflammation
Emphysema Acinus Airspace Tobacco smoke Dyspnoea
enlargement and
wall destruction

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

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COPD in some patients. The key aetiological factors in COPD are smoking (major risk),
environmental pollutants (e.g. occupation – mines, dust) and 1-antitrypsin deficiency.

Bronchial Obstruction

1.0 INTRODUCTION

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.

2.0 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

Diagram 4.1: Bronchial Obstruction

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3.0 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
 Explain the pathophysiology of the effects above.
 What investigations will be relevant in such patients

EMPHYSEMA

1.0 INTRODUCTION

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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

Diagram 4.2: Emphysema

2.0 AETIOLOGY

The main factors are -

1. Smoking – major risk factor that is dose related

2. 1-antitrypsin deficiency – a protease inhibitor that prevents lung damage especially in
smokers
3. Occupation – dustyenvironmente.g. coal mines

3.0 PATHOGENESIS

 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
 -1-antitrypsin (-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
 Deficiency of -1-antitrypsin occurs in homozygous states however in smoking
accelerates the damage in heterozygous situations
 Smoking
 Reduces anti-elastase and increases elastolytic protease in the lungs due to oxidants
in cigarette smoke which inhibit 1-antitrypsin
 Smokers have increased phagocytes and neutrophils in the lungs

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 After the damage the pressure inspired air expands the damaged portion into an
emphysematous space
 With continued enlargement more pressure is required to cause further dilatation
resulting in increased dilatation and damage
 Coughing in chronic bronchitis aggravates the situation

Diagram4.2: Pathogenesis of Emphysema

Smoking

4.0 PATHOLOGY

Macroscopy

 Voluminous pale lungs

 Dilatation of air spaces

Microscopy

 Dilatation of air spaces

 Destruction of septal wall resulting in thin walls
 Compressed capillaries
 Rupture of walls producing honeycombs

5.0 CLASSIFICATION

Classification is based on anatomical distribution within the lobule.

a) Centrilobular/centriacinar
b) Panaacinar/panlobular
c) Paraseptal/distal acinar
d) Irregular

5.1. Centrilobular/Centriacinar

 Predominant in male smokers and chronic bronchitis

 Central or proximal parts of the acinar are involved
 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).

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 Distal acinar are spared
 Associated with cigarette smoking, chronic bronchitis and inflammation of distal
airways

5.2. Panacinar (Panlobular) Emphysema

 Affects all acinar

 Acinar uniformly enlarged from the level of the respiratory bronvhioles to the terminal
blind alveoli
 Associated with 1-antitrypsin deficiency

5.3. Distal Cinar (Paraseptal) Emphysema

 affects distal portion of the acinus

 proximal portions of the acinus are spared
 usually due to infections accompanied by inflammatory changes and fibrosis

5.4. Irregular Emphysema

 Acinar irregularly affected

 Mainly associated with scarring
 Most common form of emphysema

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Diagram 4.3: Types of Emphysema

6.0 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

7.0 COMPLICATIONS
1) Corpulomonale TASK
2) Congestive Cardiac failure
3) Pulmonary hypertension  Compare and contrast emphysema and
chronic bronchitis.
8.0 CAUSES OF DEATH  State the important investigations

1) Respiratoryacidosis
2) Coma
3) Right sidedheartfailure
4) Massive lung collapse due to pneumothorax

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Lesson 5: Bronchiectasis and Bronchitis

Learning Outcomes

At the end of the lesson, the learner should be able to -

1. Describe causes and effects of bronchiectasis

2. Diagnose bronchial obstruction, emphysema and bronchiectasis

1.0 INTRODUCTION
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 [Link] 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.

2.0 AETIOLOGY

There are two 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,
Heamophilusinfluenzae, 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.

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Associated Conditions

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

congenital factors

1. Congenital and hereditary conditions

a. Cystic fibrosis
b. Intralobular sequestration of the lung
c. Immunodeficiency states
d. Kartagener’s syndrome ((Bronchiectasis, sinusitis, displacement of viscera (heart) –
immobility of the cilia
e. Congenital bronchiectasis
f. Atelectasis

2. Post infection conditions

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

3. Bronchial obstruction
a. Tumours
b. Foreign bodies
c. Mucous impaction

4. Others
a. Bronchiolitis and bronchopneumonia in childhood
b. Rheumatoid arthritis
c. S.L.E
d. Inflammatory bowel syndrome
e. Post-transplant

3.0 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

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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.

Diagram 5.1: 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)

Diagram 5.2: Pathogenesis – Infections

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4.0 PATHOLOGY

Macroscopy What is the relationship

between Bronchiectasis and
1. Dilated bronchi with thickened walls cystic fibrosis
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
 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

5.0 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

6.0 DIAGNOSIS

1. Bronchophony
2. Bronchoscopy

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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

7.0 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. Corpulmonalae
6. Amyloidosis
7. COPD
8. Recurrent pneumonia

BRONCHITIS

Acute Bronchitis

This is inflammation of the large and medium bronchi.

Aetiology

1. Viral
a. Respiratory syncytial virus f. Herpes viruses
b. Rhinovirus g. Coxsackie viruses
c. Echovirus h. Corona viruses
d. Parainfluenza types 1, 2 3 i. Adenoviruses
e. Influenza j. Measles

2. Mycoplasma - Candida albicans, Candida tropicalis, Histoplasmacapsulatum 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

 Invasion by virus leads to inflammatory reaction by the bronchial epithelium

 There is activation of the mucous and serous glands leading to production of mucous
secretions that cause crackles on auscultation.

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 The ciliated epithelium aids in pushing the exudate upwards preventing spread into the
bronchioles.
 Spread of the inflammatory reaction to involve the bronchioles in debilitated subjects
results in bronchiolitis and bronchopneumonia which is fatal.
 Because of inflammatory oedema there is reduction in lumen size resulting in wheezing
and rhonchi.

Pathology

Macroscopy

 Congested
 Swollen/oedematous
 Hyperaemia
 Tenacious mucous exudate
 Sputum – yellow/green

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Microscopy
 Congested mucosa
 Infiltration by neutrophils

Clinical Features
 Cough – initially unproductive but later yellow/green sputum.
 Wheezes/rhonchi
 Crepitations
 Shortness of breath
 Fever
 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

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Diagram5.3: Evolution of Chronic Bronchitis

Bronchiolar and
Bronchial injury

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
 Hyperaemia and oedema of mucous membrane
 Mucous secretions
 Increased size of mucous glands
 Plugging of bronchi and bronchioles
 Fibrosis
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 Inflammatory changes

Microscopy

 Venous congestion
 Metaplasia
 Hypertrophy
 Dysplasia
 Inflammatory cells
 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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Lesson 6: Bronchial Asthma

Learning Outcomes

At the end of the lesson, the learner should be able to: -

1) Describe the causes of asthma

2) Describe the pathogenesis and pathophysiology of asthma
3) Investigate a patient with asthma
4) Discuss complications of asthma

1.0 INTRODUCTION
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.

2.0 AETIOLOGY

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

3.0 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

3.1. 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.

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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-sensitizedIgE 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 ofbronchoconstriction,
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.

Diagram 6.1: Progression in Asthma

Hypersensitivity

Hypersensitive airway disease

Bronchitis

Asthma (overt)

3.2. 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.

3.3. 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 bronchoconstritiveleukotrienes.

3.4. Occupational Asthma

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

4.0 PATHOGENESIS

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

Inflammation and Airway obstruction

4.1. 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.

4.2. 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, T helper lymphocytes, oesinophils and
mast cells, which is a common feature in asthma.

4.3. 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

4.4. 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 D 2 (PD2) and leukotrienesC4 (LTC4) that
cause the immediate asthmatic reaction. Note that 2adrenoreceptor e.g. salbutamol
inhibit release of mediators by the mast cells.

4.5. The Epithelium

Following the inflammatory reaction, epithelial cells shed during exacerbations of
asthma results in desquamations, which increase permeability of the airway to inhaled
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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.

4.6. 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  and 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.

5.0 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 -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. 2 agonists and theophylline can prevent the contraction.

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6.0 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)

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

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

7.0 CLINICAL FEATURES

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

 Main Features include – cough, headache, difficulty in breathing, hyperventilation,

wheezing and chest pain/tightness

 Severe asthma
o Inability to complete a sentence in one breath
o Respiratory rate > 25 breaths per minute
o Tachycardia > 110 (pulsusparadoxicus)
o PEFR< 50% of predicted normal best
 Life threatening asthma
o Silent chest, cyanosis or feeble respiratory effort
o Exhaustion, confusion or coma
o Bradycardia, hypotension
o PEFR< 30%

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8.0 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
a. External compression (thoracic, superior vena cava syndrome, substernal
thyroid)
b. Intrinsic airway – pulmonary lung cancer and metastatic breast cancer
2. Pulmonary emboli

9.0 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.
 Peak flow charts – take PEFR on walking, middle of the day and before bed. It
shows reduced PEFR, MMEFR
 Reduced FEV1

Diagram6.2: Lung Volumes

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Diagram6.3: FEV

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

FEV1 x 100/sec (the normal ratio is 80 – 97%)

FVC

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 PaO 2 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
 Charcot Leyden spirals
 Curschmann’s crystals
 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

10.0 COMPLICATIONS
1.
What is the pathophysiology of
these
complications?

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2. Pneumothorax
3. Pneumomediastinum
4. Respiratory failure
5. Heart failure/CCF
6. CorPulmonale
7. COPD

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Lesson 7: Restrictive Pulmonary Diseases

Leaning Outcomes

At the end of the lesson, the learner should be able to: -

1) Classify restrictive diseases of the lungs

2) Describe the pathogenesis and pathology of restrictive lung diseases
3) Explain the features and complications
4) Investigate patients with restrictive lung diseases

1.0 INTRODUCTION

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 [Link]
restrictive lung disease is characterized by reduced expansion of the lung parenchyma
with reduced total lung capacity.

2.0 CLASSIFICATION

There are three types: -

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

a. Kyphosis
b. Poliomyelitis
c. 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
3.0 PATHOGENESIS

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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.

Diagram 7.1: Pathogenesis of Restrictive Lung Disease

Stimuli

4.0 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) Corpulmonale
9) Reduced CO diffusing capacity
10) Reduced lung volume
11) Reduced lung compliance

5.0 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. Find out the
inorganic (mineral
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(biologic) dusts
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

6.0 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

7.0 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. Corpulmonale

8.0 ASBESTOSIS

Introduction
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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

 Insidious onset
 Dyspnoea
 Cough – dry or productive
 Pulmonary hypertension
 Corpulmonale
 Various forms of cancer

9.0 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(Disaminated intraverscular coagulation)
8) Massive blood transfusion
9) Acute pancreatitis
10) Radiation injury

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Pathogenesis

Diagram 7.2: Pathogenesis of ARDS

Progression to fibrosis of alveoli

10.0 IMMUNOLOGIC LUNG DISEASE

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

Table 1: Pathophysiology of Restrictive Lung Diseases

Disease Pathogenesis/pathology
Bronchial asthma Explain
Hypersensitivity (allergic)  Immune mediated inflammation of the lung tissues
pneumonitis  Examples – Farmer’s lung, Bird breeders lung, Malt
workers lung, Mushroom workers lung
Pulmonary Eosinophilia  Immunological meditated lung diseases characterized
by infiltration of the lungs and elevated eosinophil
counts e.g. Loeffler’s syndrome
Good Pastures Syndrome  Necrotizing haemorrhagic interstitial pneumonitis

11.0 VASCULAR COLLAGEN DISEASE

Table 2: Pathogenesis of Restrictive Lung Disease in Vascular Collagen Disease

Disease Pathogenesis/pathology
Rheumatoid arthritis  Pleural effusion
 Interstitial pneumonitis
 Rheumatoid pneumoconiosis
S.L.E  Pleurisy
 Pleural effusion
 Interstitial pneumonitis
 Pulmonary haemorrhage
 Vasculitis

Compare and contrast obstructive and restrictive lung diseases

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Lesson 8: Pulmonary Infections 1 – Bacterial
Pneumonia

Learning Outcomes

1) Identify causes of pulmonary infections

2) Discus predisposing factors to pulmonary infections
3) Describe the pathology of different types of pneumonia
4) Compare and contrast bronchopneumonia and lobar pneumonia
5) Investigate patients with pulmonary infections
6) Discuss complications of pulmonary infections

1.0 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

1.0 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).
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2.0 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 [Link] 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.

3.0 ROUTES OF INFECTION

The microorganims gain entry into the lungs via: -

1. Inhalation of microbes present in the air

2. Aspiration – naso and orophartnx
3. Haematogenous spread from a distant foci of infection
4. Direct spread from an adjacent site of infection

4.0 CAUSES OF PNEUMONIA

Table 1: Causes of Pneumonia

Type of Pneumonia Causes
Community acquired acute  Streptococcus pneumoniae
pneumonia  Haemophilusinfluenzae
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  Moraxella catarrhalis
 Staphylococcus aureus
 Legionella pneuomophila
 Enterobacteriae – (Klebsiellapneumoniae) and
Pseudomonas spp
Community acquired  Mycoplasma pneuominaie
atypical pneumonia  Chlamydia spp (C. pneumoniae, C. psittaci, C.
Trachomatis
 Coxiella burnetti (Q-fever)
 Virues – Respiratory syncitial virus,
parainfluenzae (children), infleunzae A and B
(adultrs) adenovirus
Nosocomial pneumonia  Gram Negative rods – Enterobacteraie
(Klebsiellaspp; Serratiamarcescens; Escherichia
coli) and Pseudomonas
 Staphylococcus aureus
Aspiration pneumonia  Anaerobic flora (Bacteroids, Fusobacterium)
mixed with aerobic bacteria (Streptococcus
pneumoniae, Staphylococcus aureus,
Haemophilusinfleunzae, Pseudomonas
aeruginosa)
Chronic pneumonia  Nocardia
 Actinomyces
 Granulomatous – Mycobacterium tuberculosis
and atypical mycobacteria,
Histoplasmacapsulatum, Blasotmycesdermatitidis
Necrotizing pneumonia and  Anaerobic bacteria
Lung abscess  Staphylococcus aureus
 Klebsiellapneumoniae
 Streptococcus pyogenes
Pneumonia in the  Cytomegalovirus
immunocompromised host  Pneumocystis jeroveci


5.0 CLASSIFICATION

Classification is based on: -

1. Aetiologic classification (Microbiological classification)

a. Bacterial – pneumococci, streptococci, staphylococcus, H. influenzae,
Mycobacterium tuberculosis, anaerobic bacteria – bacteroids
b. Viral – adeno viruses, pircona viruses, rhino viruses, arbo viruses, coxsackie,
myxovirus, myxovirusparainfluenzae, respiratory syncitial virus and psittacosis
virus
c. Rickesttsiae – Coxellaburnetti
d. Protozoa - Pneumocystis carinni, Toxoplasma gondii
e. Mycoplasma – Mycoplasma pneumoniae
f. Fungal – Candida albicans, Histoplasmosis, Coccidomycosis, Cryptokocosis
(Cryptococcus neofomans), Apsergilusfumigutus (aspergillosis, aspergiloma)
g. Chemical – kerosene, aspiration, lipid pneumonia

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2. Pathologic classification – how the infection spreads within the lung
a. Lobar pneumonia
b. Bronchopneumonia

3. Clinical classification – circumstances surrounding development of disease

a. Community acquired disease
b. Hospital acquired (nosocomial) infections
c. Post-operative pneumonia
d. Aspiration pneumonia
e. Obstructive pneumonia
f. Disease acquired in special environments
g. Disease in immunosuppressed patients

6.0 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

1.0 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.

2.0 AETIOLOGY

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

1. Pneumococcal pneumoniae (Streptococcuspneumoniae) – 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

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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), Klensiellapneumoniae (Frielander’s bacilli),
Pseudomonas aeroginosum, Proteus, Escherichia coli

3.0 PATHOGENESIS

The microbes gain access to the lungs via several routesbecause 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.

Diagram 81: Lobar Pneumonia

4.0 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
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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

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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 3 rd 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

5.0 CLINICAL FEATURES

1. Sudden onset
2. Symptoms
 Shaking, chills
 Hotness of the body
 Malaise
 Pleuritic chest pain
 Dyspnoea
 Cough with expectoration – mucoid, purulent or bloody sputum

3. Signs
a. General – fever, tachycardia, tachypnorea, cyanosis
b. Respiratory system

6.0 INVESTIGATIONS

1. Full haemogram – neutrophils leucocytosis, raised ESR

2. Positive blood cultures
3. Sputum examination
4. Chest X-ray – consolidation
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7.0 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)
a. Pericardium – pericarditis, myocarditis, endocarditis
b. Otitis media, Mastoiditis
c. Meningitis
d. Brain abscess
e. Purulent arthritis
f. Peritonitis
11. Renal failure, Multiple organ failure

Bronchopneumonia

1.0 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.

2.0 PATHOGENESIS

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

Diagram 8.2: Bronchopneumonia

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3.0 AETIOLOGY

1. Staphylococcus
2. Streptococcus
3. Pneumococci
4. Klebsiellapneumoniae
5. Heamophilusinfluenzae
6. Gram negative bacilli – Pseudomonas
7. Coliform bacteria

4.0 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

Table 2: Differences Between Lobar and Bronchopneumonia

Feature Lobar pneumonia Broncho pneumonia
Definition Acute bacterial infection of a part of a lobe Acute bacterial infection of the
of one or both lungs or the entire lobe(s) terminal bronchioles extending in to
the adjoining alveoli
Age group More common in adults Common at extremes of ages –
infants and old age
Predisposing More often affects healthy persons Pre-existing disease
factors
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Common Pneumococci, Klebsiella pneumonias, Staphylococcus, Streptococcus,
aetiologic agents Staphylococcus, Streptococcus Pseudomonas,
Heamophilusinfleunzae
Pathologic  Congestion (1-2 days)  Patchy consolidation
features
 Early (red hepatisation) 2 – 4 days  Alveolar exudation
 Late consolidation (grey hepatisation)
4 – 8 days
 Resolution (1 – 3 weeks)
Investigations  Neutrophil leucocytosis  Neutrophil leucocytosis
 Positive blood culture  Neutrophil leucocytosis
 X-ray shows consolidation  X-ray shows spotted focal
opacities
Prognosis Good response to treatment, resolution is Variable
common, good prognosis Prognosis poor
Complications  Pleural effusion  Bronchiectasis
 Empyema  Pleural effusion
 Lung abscess  Empyema
 Organization  Lung abscess
 Organization

5.0 CLINICAL FEATURES

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

6.0 INVESTIGATIONS
1. Chest X-ray – shows mottled, focal opacities in both lungs, chiefly in the lower
zones
2. Total Blood counts

7.0 COMPLICATIONS

1. as lobar pneumonia
2. Bronchiectasis

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Lesson 9: Pulmonary Infections 2 – Other Types of
Pneumonia

Aspiration Pneumonia

1.0 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.

2.0 PREDISPOSING FACTORS

1. Altered consciousness
a. Alcoholism
b. Seizures
c. Cerebrovascular accidents
d. Head trauma
e. General anaesthesia
f. 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

3.0 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.

3.1. 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.

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

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3.2. BACTERIAL INFECTION
Introduction
Bacterial infection is the most common form of aspiration pneumonia. Bacteria such as
Streptococcuspneumoniae, Heamophilusinfluenzae, gram-negative bacilli and
Staphylococcusaureus 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.

3.3. 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.

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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
What are the complications of aspiration pneumonia?

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 Which microbes will stand accused in hypostatic pneumonia?

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
a. Reduced immune defence (steroid treatment, malignancy, diabetes)
b. Reduced cough reflex e.g. post operative
c. Disordered mucociliary clearance e.g. anaesthetic agents
d. Bulbar or vocal cord palsy
2. Aspiration of nasopharyngeal or gastric secretions
a. Immobility
b. Reduced consciousness
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 c. Vomiting, dysphagia, achalasia or severe reflux
d. Nasogastric intubation

3. Bacteria introduced into the lower respiratory tract

a. Endotracheal intubation
b. Tracheostomy
c. Infected ventilators/nebulizers/bronchoscopes
d. Dental or sinus infection

4. Bacteraemia
a. Abdominal sepsis
b. Infected emboli
c. Intravenous cannula infection

Atypical STUDY QUESTIONS

Pneumonia 1. What are causes of atypical pneumonia?
2. What are the predisposing factors?
3. What investigations will be relevant?
4. What are the complications of atypical pneumonia?

STUDY QUESTIONS

In pulmonary disease in HIV infection, viral pneumonia and

chronic pneumonia

1. Which microorganisms are responsible?

2. What are the clinical features?
3. What is the pathophysiology?
4. What are the predisposing factors?
5. What are the complications?

Differential Diagnosis of Pneumonia

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

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Lesson10: Pulmonary Infections 3– Lung Abscess

1.0 INTRODUCTION

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).

2.0 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.

3.0 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

4.0 AETIOLOGY

1. Bacteria - Streptococcuspyogenes (Group A -haemolytic),

Streptococcuspneumonia, Staphylococcusaureus, Anaerobic bacteria, Entero Gram
negative bacteria – Klebsiella, Mycobacterium – Mycobacterium tuberculosis,
Pseudomonasaeruginossa, Pseudomonaspseudomallaei, Legionella, H. Influenza,
Nocardia
2. Actinomycosis
3. Fungi –Cryptococcus neoferan, Aspergillus, Histoplasmacapsulatum
4. Parasites – Entamoebahistolytica

5.0 MECHANISM OF INFECTION (PATHOGENESIS)

A. Preceding Bacterial Infections (inoculation)

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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

Diagram 10.1: Sites of Abscess in Bacterial Infections

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?)

Diagram 10.2: Sites of Abscess following Aspiration/inhalation

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

Diagram 10.3: Sites of Abscess in Bronchial Obstruction

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

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

6.0 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.

7.0 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

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8.0 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

9.0 DIAGNOSIS

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

10.0 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

11.0 INVESTIGATIONS

STUDY QUESTIONS

1) What investigations would be important in a patient with lung abscess?

2) State the important parameters in the investigations above
3) Outline important features in the history of a patient with pneumonia
4) Discuss physical examination findings in a patient with severe penumonia

12.0 STUDY QUESTIONS

1. What is the pathophysiology of these

complications

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

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Lesson 11: Pulmonary Tuberculosis

Learning Outcomes

At the end of the lesson, the learner should be able to: -

1) Discuss the pathology of lung abscess

2) Discuss the pathology of tuberculosis

Pulmonary Tuberculosis

1.0 INTRODUCTION

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).

2.0 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 [Link] 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.

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Diagram 11.1: Chest Radiograph in PTB

3.0 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.

4.0 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) TBand the
probability of transmission from one person to another depends upon the number of
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infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of
exposure, and the virulence of the M. tuberculosisstrain.

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

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.

5.0 PREDISPOSING FACTORS

1. Debilitating or immunosuppressive conditions

a) Diabetes mellitus
b) Chronic lung disease
c) End stage renal disease
d) HIV/AIDS
e) Alcoholism
f) Hodgkin’s disease
2. Smoking
3. Inadequate medical care
4. Poverty
5. Crowding
6. Malnutrition

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6.0 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 [Link] 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.
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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.

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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.

7.0 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.
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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 [Link] exudative phase follows rapidly
and forms three patterns: -

1. Fibrinomacrophagicalveolitis
 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. Polymorphonuclearalveolitis
 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. Fibrinousalveolitis
 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.

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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 [Link] 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 [Link]
forms a hard [Link] 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
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macrophages. The soft tubercle, which is a fully developed granuloma with caesous
centre, does not favour rapid proliferation of tubercle bacilli.

8.0 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

9.0 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.

Diagram 11.2: Spread of PTB

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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.

10.0 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.

10.1. 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)

Diagram 11.3: Primary Complex

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Pulmonary Component (Ghon’s Focus)

The Ghon’s focus is the lesion in the lungs thatis 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 tabesmesenterica. 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.

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8. Mechanical effects – large granulomas can obstruct the bronchi leading to hypoxia
and lung collapse (atelectasis)

10.2. 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.

Diagram 11.4: Lesions in Secondary Infection

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.
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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, tuberculouscaseous 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.

11.0 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

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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.

12.0 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
 Fever,
 Night sweats
 Fatigue
 Weight loss
 Loss of appetite
 Lymphadenopathy

 Lungs
 Productive cough
 Haemoptysis
 Pleural effusion
 Dyspnoea
 Orthopnoea
 Lung collapse
 Monophonic wheeze
 Bronchiectasis often in the middle lobe (Brock’s syndrome)
 Examination –IPPA

13.0 INVESTIGATIONS AND DIAGNOSIS

1. History and physical examination

What are the important parameters in these
2. Imaging (Chest X-ray)
investigations?
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3. Sputum examination
4. Total blood counts
5. Fibreoptic bronchoscopy
6. Biopsies

14.0 CAUSES OF DEATH

STUDY Q

1. What are the causes of death in PTB?

15.0 DIFFERENTIAL DIAGNOSIS STUDY Q

1. What are the differential diagnoses?

16.0 COMPLICATIONS

1. Pleurisy STUDY Qs
2. Pneumothorax
3. Empyema or pyopneumothorax 1. Explain the pathophysiology of these
4. Tuberculous laryngitis complications.
5. Tuberculous enteritis 2. What is miliary tuberculosis?
6. Ischiorectal abscesses 3. What are the features of miliary TB
7. Blood borne dissemination 4. Explain how tuberculosis affects other organs
8. Respiratory failure in the body (extra-pulmonary tuberculosis).
9. Cardiac failure

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Lesson 12: Pulmonary Vascular Disease and Acute
Lung Injury

Learning Outcomes

At the end of the lesson, the learner should be able to -

1) Discuss the causes of pulmonary vascular disease

2) Discuss the pathology of pulmonary oedema
3) Discuss the pathology of pulmonary hypertension
4) Discuss the pathology of pulmonary embolism and infarction
5) Discuss the pathology of pulmonary respiratory distress syndrome

1.0 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

1.0 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”.
2.0 CAUSES

1) Haemodynamic disturbances (haemodynamic/cardiogenic oedema)

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 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)

3.0 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)
4.0 PATHOLOGY

Macroscopy

 Wet heavy lungs

 Soggy lungs

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Microscopy

 Engorged alveolar capillaries

 Alveolar microhaemorrhages
 Haemosiderin-laden macrophages (heart failure cells)
 Fibrosis and thickening of alveolar walls

5.0 CLINICAL FEATURES

 What are the clinical features?

6.0 INVESTIGATIONS
 What investigations will be relevant?
 What parameters will be significant in these investigations?

7.0 COMPLICATIONS
 Outline the complications stating their pathophysiology and
differentiating factors

PULMONARY HYPERTENSION

1.0 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(chronic obstructive

airway disease), 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 (Corpulmonale)

2.0 CLASSIFICATION

Can be classified as -

1) Primary
2) Secondary

3.0 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.
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Pathogenesis
 Unknown

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

1) Passive pulmonary hypertension

 Commonest
 Produced by lesions that increase pressure in the pulmonary veins (pulmonary
venous congestion)
o Mitral valve disease (mitral stenosis)
o 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
 Multiple emboli/thrombosis
 SCD
 Schistosomiasis
 Foreign body emboli (e.g. in drug addicts)
b. Obliteration – reduced pulmonary vascular bed by chronic parenchymal lung
disease (destruction of lung capillary bed)
 Chronic emphysema, Chronic bronchitis
 Bronchiectasis, Pulmonary tuberculosis
 Pneumoconiosis
 Interstitial fibrosis
c. Vasoconstrictive - widespread sustained hypoxia results in vasoconstriction and
alveolar hyperventilation and pulmonary hypertension
 High altitude
 Pathologic Obesity (Pickwickian syndrome)
 Severe hyphoscoliosis
 Upper airway disease causing tonsilar hypertrophy

4) Idiopathic
5.0 PATHOLOGY

Heart

 Right ventricular hypertrophy

 Right atrial dilatation

Arteries and small pulmonary arteries

 Medial hypertrophy
 Thickening and reduplication of elastin

Medium sized arteries

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 Medial hypertrophy
 Intimal thickening
 Thickening of elastic
 Adventitial fibrosis

Large arteries

 Atheromatous deposits
What are the clinical features?
6.0 CLINICAL FEATURES

 What investigations will be relevant?

7.0 INVESTIGATIONS  What parameters will be significant in these
investigations?

 Outline the complications stating their

8.0 COMPLICATIONS pathophysiology and differentiating factors

Adult Respiratory Distress Syndrome (Diffuse

Alveolar Damage)

1.0 INTRODUCTION

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.

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2.0 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

3.0 PATHOGENESIS

Diagram 8.1: Pathogenesis of ARDS

Acute Alveolar Damage

4.0 PATHOLOGY

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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

5.0 CLINICAL FEATURES

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

6.0 INVESTIGATIONS

1) Chest X-ray - diffuse bilateral infiltrates

2) Lung volumes
3) Blood counts

7.0 COMPLICATIONS  Outline the complications stating their

pathophysiology and differentiating factors

PULMONARY EMBOLISM AND INFARCTION

1.0 INTRODUCTION

Most emboli arise from deep leg veins (calf, popliteal, femoral and iliac veins) and
passes in the venous circulation into the right heart and to the pulmonary arteries.
Pulmonary embolism is a common preventable condition that can cause arterial
occlusion resulting in infarction.

There are two main consequences of embolization to the pulmonary arterial tree –
increased pulmonary arterial pressure (affects right heart) and ischaemia of the lungs. If
60% of pulmonary vasculature is blocked suddenly (massive pulmonary embolism), the
heart cannot pump blood (cardiovascular collapse) through the lungs causing sudden
death. Blockage of middle-sized arteries results in major pulmonary embolism. 80% of
the cases result in small emboli (minor pulmonary embolism)

2.0 PREDISPOSING FACTORS

1) Immobility and bed rest

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2) Post operative period
3) Pregnancy and post partum
4) Oral contraceptive therapies with high oestrogen preparations
5) Nephrotic syndrome
6) Severe burns
7) Trauma
8) Cardiac failure

3.0 CAUSES 1) What are the causes?

2) What is the pathogenesis of pulmonary embolism?

4.0 TYPES OF EMBOLI

1) Thromboembolism
2) Air
3) Bone marrow
4) Fat
5) Amniotic fluid
6) Foreign body
5.0 PATHOPHYSIOLOGY

Pathophysiologic response and clinical significance depends on extent of obstruction,

number of emboli, status of the cardiovascular system and release of vasoactive
amines(histamine or cerotenin).

6.0 CLINICAL FEATURES

1) Chest pain
2) Dyspnoea
3) Tachypnoea
4) Fever
5) Cough
6) Haemoptysis
7) Pleural rub
8) Severe – sudden death

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Lesson 13: Tumours of the Lungs

Learning Outcomes

At the end of the lesson, the learner should be able to: -

1) Classify tumours of the lungs

2) Discuss the pathology of tumours of the lungs
3) Diagnose tumours of the lungs

1.0 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.

2.0 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 – atmosphericpollutants – 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

3.0 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
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 a. Benign mesothelioma
b. 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 LIKELESSIONS

1) Harmatomas
2) Eosinophilic granuloma
3) Inflammatory pseudotumours

4.0 PATHOLOGY

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

Diagram 13.1: Sites of Tumour Origin

Macroscopy

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

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Microscopy

What microscopic picture do you expect?

5.0 SPREAD

1) Local spread

 Through the wall into the surrounding lung tissues and pleural cavity
 Peribronchial spread
 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)
 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)

Diagram 13.2: Spread of Tumour

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2) Lymphatic
 Ipsilateral and contraleteralhilar and peribronchial lymph nodes
 Metastasis – mediastinal, cervical, supraclavicular, paraortic
 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

6.0 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
a. Fever
b. Weight loss
c. Anaemia
d. Jaundice

2) Local symptoms
a. Cough
b. Chest pain
c. Dyspnoea
d. Haemoptysis

Causes of Haemoptysis

a) Inflammatory
 Bronchiectasis
 Bronchitis
 Tuberculosis
 Lung abscess
 Pneumoconiosis

b) Neoplastic
 Primary and metastatic lung cancer
 Bronchial adenoma

c) Others
 Pulmonary thromboembolism
 LVF
 Mitral stenosis
 Primary pulmonary hypertension
 Foreign body
 Trauma
 Haemorrhagic diathesis

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3) Bronchial obstruction symptoms
a. Bronchopneumonia
b. Lung abscess
c. Bronchiectasis
d. Pleural effusion
e. Productive cough

4) Symptoms due to metastasis

a. Superior vena cava syndrome
b. Painful bony lesions
c. Pathological fractures
d. Paralysis of recurrent laryngeal nerve
e. Neurologic manifestations
f. Hepatomegally

5) Paraneoplastic– ectopic hormone production

a. ACTH  adrenal hyperplasia  increased blood cortisol  Cushing syndrome
b. ADH water retention dilutionalhyponatraemia
c. Parathyroid hormone hypercalcaemia
d. Calcitonin  hypocalcaemia
e. Gonadotropins gynaecomastia

6) Other systemic manifestations

a. Neuromuscular - Myopathy , Peripheral neuropathy
b. Skeletal - Digital Clubbing, Hypertrophic osteodystrophy
c. Cutaneous - Acanthosisnigrans
d. Cardiovascular - Migratory thrombophlebitis (Trousseaus syndrome)
e. Haematologic- Abnormalities in coagulation

7.0 COMMON HISTOLOGICAL TYPES OF BRONCHOGENIC

CARCINOMA

1) Squamous cell carcinoma

 Most common bronchogenic carcinoma

 Derived from metaplastic squamous epithelium
 M>F
 Strong association with cigarette smoking
 Arise in central bronchus (central)
 Causes bronchial obstruction
 Exhibits rapid spread

2) Adenocarcinoma

 F > M (commonest bronchogenic carcinoma in women)

 Develops as a peripheral tumours (may occur centrally)
 Slow growing
 Associated with areas of chronic scarring
 Weak association with cigarette smoking
 4 main types – acinar (gland like) occurring in large bronchi, papillary (frond of
tumour on thin septa) in the lung periphery, bronchoalveolar (papillary,

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 cuboidal tall columnar and mucous secreting epithelium) and solid carcinoma
(poorly differentiated, lacks acinar, tubes or papillae)

3) Small cell carcinoma

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

4) Large cell carcinoma

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

8.0 DIAGNOSIS AND INVESTIGATIONS

1) History
2) High index of suspicion
3) Physical examination
4) Investigations
a. Chest X-ray
b. Sputum examination
c. Pleural effusion tap – analysis
d. Bronchoscopy and biopsy
e. Blood counts
f. Liver function tests
g. Renal function tests

9.0 COMPLICATIONS What are the complications of tumours of the lungs?

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10.0 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 Ipsilateralhilar or peribronchial nodal involvement
N2 Metastasis to ipsilateralmediastinal or subcarinal lymph nodes
N3 Metastasis to contralateral mediastinal or hilar lymph nodes, ipsilateral or
contarlateralscalenae 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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Lesson 14: Disorders of the Pleura and
Mediastinum

Learning Outcomes

At the end of the lesson, the learner should be able to: -

1) Outline disorders of the pleura

2) Discuss the pathology of pleural effusion
3) Discuss the pathology of pneumothorax
4) Discuss the pathology of chest injury

DISORDERS OF THE PLEURA

1.0 INTRODUCTION

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

2.0 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)
 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
 Exudates - high protein fluid (with fibrinogen/fibrin) due to movement of
fluid through damaged vessel walls commonly due to infarctions,
infection or tumours
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NOTE: There could be accumulation of air (pneumothorax)

PLEURAL EFFUSION

1.0 INTRODUCTION

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.

2.0 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.

Diagram 14.1: Formation of Pleural Fluid

3.0 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.

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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.

3.1. 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 mediastinalcarcinomatosis

Diagram 14.2: Pleural Effusion

4.0 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

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

Causes
1) Infections
a. Bacterial infections e.g. pneumonia (Streptococcus pneumoniae, Haemophilus,
Klebsiella, Pseudomonas, Bacteroiods)
b. Tuberculosis
c. Fungal infections
d. Viral infections
e. Parasitic infections
2) Neoplastic
a. Metastatic tumours – breast, lungs, lymphoma, ovary, genito-urinary, G.I.T, and
melanoma
b. Mesothelioma (primary tumours)
3) Pulmonary infarction – thromboembolic disease

4) GIT Diseases
a. Eosophageal perforation
b. Pancreatic disease
c. Intra-abdominal abscess
d. Diaphragmatic hernia
e. After liver transplant
f. Subphrenic abscess
5) Collagen-vasculardisease - Rheumatoidpleuritis, S.L.E.
6) Iatrogenic injury
7) Drug induced pleural disease – Nitrofurantoin, Bromocriptine
8) Ovarian hyperstimulation syndrome
9) Pericardial disease
10) Radiation therapy

5.0 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

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Causes

a) Infection
 Usually due to spread from pneumonia and tuberculosis
 Following penetrating chest injury e.g. stab wounds

b) Auto-immune
 Rheumatoid arthritis
 S.L.E

c) Overlying a pulmonary infarct

Diagram 14.3: Pleural Effusion 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.

Diagram 14.4: Fibrous Exudate

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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

 Loculated yellowish-green creamy pus (large volumes)

 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

6.0 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

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Investigations

Chest X-ray
 Obliterated costodiaphragmatic angle
 Opacities
 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.

7.0 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

  chest movement
  chest expansion
 Deviated trachea
  breath sounds
 Aegophony
 Stony dull percussion

2) Features of respiratory distress

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8.0 DIAGNOSIS OF PLEURAL EFFUSION

Procedure Features
History  Shortness of breath
 Pleuritic chest pain
 Unproductive cough
Examination   chest movement,  chest expansion
 Deviated trachea,  breath sounds
 Aegophony
 Stony dull percussion
Radiology  Chest X-ray, Ultrasound
 CT scan
Pleural aspiration  Gross appearance
 Biochemistry
 Cytology, Microbiology
Pleural biopsy  Histology
Thoracoscopy  Gross appearance, Pleural fluid, cytology
 Pleural biopsy
9.0 INVESTIGATIONS

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

2) Pleural effusion aspiration

a. Gross appearance
b. Biochemistry
c. Cytology
d. Microbiology
e. Histology
3) Blood counts
4) Thoracoscopy

THORACIC TRAUMA

1.0 INTRODUCTION

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
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3) Haemothorax
4) Sternal fractures
5) Diaphragm
6) Lungs
7) Mediastinum
8) Heart

Penetrating Thoracic Trauma

1) Wounds
2) Viscera
a. Lungs
b. Heart
c. Oesophagus
d. Thoraco-abdominal

2.0 BLUNT INJURIES

2.1. 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.

2.2. 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).

2.3. Sternal Fractures

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

2.4. 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.

2.5. Lungs

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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.

2.6. Mediastinum

Severe deceleration results in rupture of mediastinal vessels.

2.7. Heart

Contusion of the heart may occur with blunt injuries.

3.0 PENETRATING INJURIES

3.1. 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.

3.2. Viscera
1) Lungs
 Laceration results in haemopneumothorax

2) Heart
 Penetration of the heart results in cardiac tamponade and precardial wounds

3) Oesophagus
 Uncommon
 Results in pneumomediastinum, mediastinitis and left hydrothorax

4) Thoraco-abdominal injuries occur due to: -

 Penetrating would below 4th ICS anteriorly, sixth ICS laterally and eight ICS
posteriorly
 Penetration by a missile (bullet wounds)

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Pneumothorax

1.0 INTRODUCTION

Pneumothorax is accumulation of air in the pleural cavity. It can be – spontaneous

(primary and secondary), traumatic and iatrogenic (therapeutic)

2.0 CAUSES

1) Spontaneous pneumothorax
a. Primary spontaneous pneumothorax
 Occurs in thin young men due to rupture of congenital sub-pleural apical
bleb

b. Secondary spontaneous pneumothorax

 Rupture of emphysematous bulla
 Asthma
 Rupture of congenital cysts
 Pleural malignancy
 Cystic fibrosis
 Pneumonia
 Sarcoidosis
 Whooping cough
 Tuberculosis
 Chronic bronchitis in old patients
 Pulmonary infarction
 Bronchial cancer

2) Traumatic pneumothorax
a. Penetrating chest wounds
b. Fracture of the ribs
c. Oesophageal rupture

3) Iatrogenic (therapeutic) pneumothorax

a. Subclaviancannulation
b. Positive pressure artificial ventilation
c. Pleural aspiration
d. Oesophageal rupture during endoscopy
e. 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.

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Diagram 14.5: Tension Pneumothorax

Diagram 14.6: Mediastinal Shift due to Tension Pneumothorax

3.0 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
Diagram 14.7: Safety Triangle

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4.0 INVESTIGATIONS What investigations will be relevant investigations?

5.0 COMPLICATIONS What complications will be seen in such cases?

Tumours of the Pleura

1.0 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.

2.0 BENIGN (SOLITARY) MESOTHELIOMA

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

Macroscopy

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 Small – enormous size
 Solitary
 Circumscribed firm mass
 Dense fibrous mass with occasional cysts filled with viscid fluid

Microscopy

 Whorls of reticula and collagen fibres

 Rarely malignant

3.0 MALIGNANT (DIFFUSE) MESOTHELIOMA

 Arise from visceral or parietal pleura

 Rare
 Highly malignant
 Associated with exposure to asbestosis
 Also arise in the peritoneum, pericardium, tunica vaginalis and genital tract

Gross

 Diffuse
 Thick
 White fleshy coating over parietal and visceral layers

Microscopy

 Malignant mesothelioma
 Features of malignant cells

Clinical Features

 Chest pain
 Dyspnoea
 Pleural effusion
 Infections
 Tumour effects

Spread

1) Locally
 Direct to the lungs
 By lymphatics to the hilar and mediastinal lymph nodes

2) Distant metastasis - to the liver

4.0 INVESTIGATIONS What investigations will be relevant investigations?

5.0 COMPLICATIONS
What complications will be seen in such cases?

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