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CLINICAL PATHOLOGY

MODULE 1 CLINICAL PATHOLOGY I

By CAREY FRANCIS OKINDA,

October 2014

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

Topics Hours

1. Introduction – Anatomy, Physiology, Pathology and

Investigations

2

2. Paediatric Lung Diseases 1

3. Disorders of Upper Respiratory Tract 1

4. Respiratory Failure and Lung Collapse (Atelectasis) 1

5. Obstructive and Restrictive Lung Diseases 2

6. Pulmonary Infections 3

7. Pulmonary Vascular Disease and Acute Lung Disease 2

8. The Pleura 2

9. Tumours 1

TOTAL 15

Lesson 1: Introduction to Respiratory System Pathology Learning Outcomes

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

1. Review the anatomy and functions of organs of the respiratory tract

2. Outline conditions and diseases that affect the respiratory system

3. Discuss investigations in respiratory disease

1.0 INTRODUCTION

Respiration is the process by which O2 is transported to and used by cells,

and CO2 produced is eliminated from the body which is a task effectively

carried out by the cooperative work of the respiratory system, red blood

cells and the circulatory system

Oxygenation of blood and elimination of CO2 is called external respiration

while utilization of O2 by cells and production of CO2 by the cell is described as internal respiration or cellular respiration

Most cells in the human body require O2 for survival and to carry out their

functions thus during their normal processes of work they use up O2 and

produce CO2 as a waste product that must be eliminated from the body.

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The normal intake of air is 7 litres/min of which 5 litres is available for

alveolar ventilation.

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 DIVISIONS AND ORGANIZATION

Divided into upper and lower tracts or divisions with 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

The upper respiratory tract comprises of nose, pharynx, nasopharynx,

oropharynx, laryngopharynx, larynx and trachea while the lower

respiratory tract has the bronchial tree and lungs (these are the passages)

Comprises of lungs and respiratory passages (airways), which work in

intimate collaboration with the thoracic cage, respiratory muscles and the

pulmonary circulation. It uses highly effective convective systems of

ventilation and circulation for long distance transport of O2 and CO2 and

uses diffusion exclusively for short distance movements of O2 and CO2

The main components of the respiratory system are: - the air pump,

mechanism for oxygen and carbon dioxide carrying, gas exchange surface,

circulatory system and regulatory mechanisms.

3.0 PHYSIOLOGY RESPIRATORY SYSTEM

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 involves physiological control mechanisms such as acid-base, water and

electrolyte balance, circulation and metabolism. Lungs are structures where

gas exchange between blood and inspired air takes place whereas the

respiratory passages are structures along which air is conveyed to and from

the lungs

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 micturition, 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

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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. Pulmonary capillary endothelial cells secrete angiotensin converting

enzyme (ACE) which activates angiotensin I into angiotensin II

b. Lung tissues synthesize prostaglandins, acetylcholine, bradykinin and

serotonin

4.0 INTRODUCTION TO PATHOLOGY OF THE RESPIRATORY SYSTEM

The prime role of the respiratory system is oxygenation of blood and

removal of carbon dioxide CO2

The function requires that air comes into close approximation with blood

through the anatomical arrangement of the alveoli and blood vessels.

1) Constant inward and outward flow of the enormous air exposes the

respiratory system to infection by both microbes present in inspired air and

by downward spread of bacteria that colonize the nose and throat

2) Inhalation of pollutants such as dust, fumes, smokes increase the incidence

of bronchitis, chronic lung disease and bronchial carcinoma

3) Vascular architecture of the lungs allows passage of blood into the lungs

during each cycle makes the lungs to be vulnerable to effects of

cardiovascular diseases. This is due to disturbance of pulmonary

haemodynamics e.g. pulmonary oedema and on the other hand, lung

diseases interfere with the pulmonary blood flow with noticeable effects on

the heart and systemic circulation because cardiac and pulmonary functions

are closely interdependent.

4) The lung is a frequent victim of malfunction elsewhere for example failure

of the left side of the heart results in pulmonary congestion and oedema,

systemic thrombosis on many occasions causes pulmonary embolism and

the lungs are a common site for secondary tumours.

Main diseases of the airways and the lungs are caused by infection and

inflammation

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.

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5.0 INVESTIGATIONS

1) Chest X-ray

Use the ABCDEFGH mnemonic

Chest X-ray - Systematic Approach

Reading a chest X-ray (CXR) requires a systematic approach.

The "right film for the right patient"

Check that the film bears the patient's name, age or hospital number too

The label may also tell features such as anteroposterior (AP) projection or

supine position

Check the date of the film to ascertain which one you are viewing

Technical details

Check the position of the side marker (left or right) against features such

as the apex of the heart and air bubble in the stomach. A misplaced marker

is more common than dextrocardia or situs inversus.

Most films are a poster anterior (PA) projection. The usual indication for AP

is a patient who is confined to bed.

AP vs PA Views

o Look at the relationship of the scapulae to the lung margins

o A PA view shows the scapulae clear of the lungs whilst in AP projection

they always overlap

o Vertebral endplates are more clearly visible in AP and laminae in PA. This

is important because the heart looks bigger on an AP view.

Lateral films

o A lateral view may have been requested or performed on the initiative

of the radiographer or radiologist. As an X-ray is a two-dimensional

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shadow, a lateral film helps to identify a lesion in 3 dimensions. The usual

indication is to confirm a lesion seen on a PA film.

o The heart lies in the anteroinferior field. Look at the area anterior and

superior to the heart; this should be black because it contains aerated

lung. Similarly, the area posterior to the heart should be black right

down to the hemidiaphragms. The degree of blackness in these two

areas should be similar, so compare one with the other. If the area

anterior and superior to the heart is opacified, it suggests disease in the

anterior mediastinum or upper lobes. If the area posterior to the heart is

opacified there is probably collapse or consolidation in the lower lobes.

The normal posture for films is erect (supine is usually for patients confined

to bed). In an erect film, the gastric air bubble is clearly in the fundus with a

clear fluid level but, if supine, in the antrum. In a supine film, blood will flow

more to the apices of the lungs than when erect.

Rotation should be minimal. This can be assessed by comparing the medial

ends of the clavicles to the margins of the vertebral body at the same level.

Oblique chest films are requested to look for achalasia of the cardia or

fractured ribs.

CXR should be taken with the patient in full inspiration but some people

have difficulty holding full inspiration (except when seeking a small

pneumothorax as this will show best on full expiration) A CXR in full

inspiration should have the diaphragm at the level of the 6th rib anteriorly

and the liver pushes it up a little higher in the right than on the left.

Penetration

o Is affected by both the duration of exposure and the power of the beam

o More kV gives a more penetrating beam

o A poorly penetrated film looks diffusely light (an x-ray is a negative) and

soft tissue structures are readily obscured, especially those behind the

heart

o An over-penetrated film looks diffusely dark and features such as lung

markings are poorly seen. Airway

Trace the lucency from the neck down towards the carina

Should be midline and you should be able to see two bronchi splitting from

it

Bones and soft tissues

Look at the shoulder joint and trace out each rib contour to check for

fractures or other abnormalities such as lytic lesions

Are both breast shadows present

Attention may be merited to apices, periphery of the lungs, under and

behind the hemidiaphragms and behind the heart

Cardiac

Check the cardio-thoracic ratio (CTR)

o The width of the heart should be no more than half the width of the chest

o About a third of the heart should be to the right and two thirds to the left

of centre o Note: the heart looks larger on an AP film and thus you cannot comment

on the presence or absence of cardiomegaly on an AP film.

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Diaphragm (e.g. flat or elevated hemidiaphragm)

Ascertain that the surface of the hemidiaphragms curves downwards, and

that the costophrenic and cardiophrenic angles are not blunted

Blunting suggests an effusion

Extensive effusion or collapse causes an upward curve

Check for free air under the hemidiaphragm - this occurs with perforation

of the bowel but also after laparotomy or laparoscopy

Edges (borders) of the heart

The left border of the heart consists of the left atrium above the left ventricle

The right border is only the right atrium alone and above it is the border of

the superior vena cava. The right ventricle is anterior and so does not have

a border on the PA chest X ray film. It may be visible on a lateral view.

To rule out lingular and left middle lobe pneumonia or infiltrates

Fields (The Lungs)

The pulmonary arteries and veins are lighter and air is black, as it is

radiolucent.

Check both lungs, starting at the apices and working down, comparing left

with right at the same level

The lungs extend behind the heart, so try to look there too

Note the periphery of the lungs - there should be few lung markings here

Disease of the air spaces or interstitium increases opacity

Look for a pneumothorax which shows as a sharp line of the edge of the lung

Gastric Bubble

Check for a lucency in the left upper abdominal quadrant

Hilum

Look at the mediastinal contours, first to the left and then to the right. The

trachea should be central. The aortic arch is the first structure on the left,

followed by the left pulmonary artery. The branches of the pulmonary artery

fan out through the lung.

Instrumentation

Look for obvious unusual opacities such a chest drain, a pacemaker or a

foreign body. This is a two-dimensional picture and so a central opacity may

not be something that was swallowed and is now impacted in the

oesophagus. It might be a metal clip from a bra strap or a hair band on a

plait.

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Interpretation

Abnormal opacities

When observing an abnormal opacity, note:

Size and shape

Number and location

Clarity of structures and their margins

Homogeneity

The common patterns of opacity are:

o Collapse

o Consolidation

o Heart and mediastinum

Collapse and consolidation

Collapse, also called atelectasis, and consolidation are caused by the

presence of fluid instead of air in areas of the lung.

An air bronchogram is where the airway is highlighted against denser

consolidation and vascular patterns become obscured.

Confluent opacification of the hemithorax may be caused by consolidation,

pleural effusion, complete lobar collapse and after a pneumonectomy.

To find consolidation, look for absence or blurring of the border of the heart

or Hemidiaphragm. The lung volume of the affected segment is usually

unaffected.

Collapse of a lobe (atelectasis) may be difficult to see. Look for a shift of the

fissures, crowding of vessels and airways, and possible shadowing caused

by a proximal obstruction like a foreign body or carcinoma.

A small pleural effusion will cause blunting of the costophrenic or

cardiophrenic angles. A larger one will produce an angle that is concave

upwards. A very large one will displace the heart and mediastinum away

from it, whilst collapse draws those structures towards it. Collapse may also

raise the hemidiaphragm

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Heart and mediastinum

The heart and mediastinum are deviated away from a pleural effusion or a

pneumothorax, especially if it is a tension pneumothorax and towards

collapse.

If the heart is enlarged, look for signs of heart failure with an unusually

marked vascular pattern in the upper lobes, wide pulmonary veins and

possible Kerley B lines. These are tiny horizontal lines from the pleural edge

and are typical of fluid overload with fluid collecting in the interstitial space.

If the hilum is enlarged, look for structures at the hilum such as pulmonary

artery, main bronchus and enlarged lymph nodes.

Chest X-ray in children

Identification of the patient are still important

A child, especially if small, is more likely to be unable to comply with

instructions such as keeping still, not rotating and holding deep inspiration

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Technical considerations such as rotation and under or over penetration of

the film still merit attention and they are more likely to be unsatisfactory

A child is more likely to be laid down and have an AP film with the

radiographer trying to catch the picture at full inspiration Assess lung volume

Count down the anterior rib ends to the one that meets the middle of the

hemidiaphragm

A good inspiratory film should have the anterior end of the 5th or 6th rib

meeting the middle of the diaphragm

More than six anterior ribs shows hyperinflation

Fewer than five indicates an expiratory film or underinflation.

Tachypnoea in infants causes trapping of air

Expiration compresses the airways, increasing resistance and, especially

less than 18 months, air enters more easily than it leaves and is trapped,

causing hyperinflation.

Bronchiolitis, heart failure and fluid overload are all causes

With underinflation, the 3rd or 4th anterior rib crosses the diaphragm. This

makes normal lungs appear opaque and a normal heart appears enlarged. Positioning

Sick children, especially if small, may not be cooperative with being

positioned

Check if the anterior ends of the ribs are equal distances from the spine

Rotation to the right makes the heart appear central, and rotation to the left

makes the heart look large and can make the right heart border disappear. Lung density

Divide the lungs into upper, middle, and lower zones and compare the two

sides

Infection can cause consolidation, as in an adult

Collapse implies loss of volume and has various causes

The lung is dense because the air has been lost

In children, the cause is usually in the airway, such as an intraluminal

foreign body or a mucous plug

Complete obstruction of the airway results in reabsorption of air in the

affected lobe or segment

Collapse can also be due to extrinsic compression such as a mediastinal

mass or a pneumothorax.

Differentiating between collapse and consolidation can be difficult or

impossible, as both are denser. Collapse may pull across the mediastinum

and deviate the trachea. This is important, as pneumonia is treated with

antibiotics but collapse may require bronchoscopy to find and remove an

obstruction. Pleural effusion

In children, unilateral effusion usually indicates infection whilst bilateral

effusion occurs with hypoalbuminaemia as in nephrotic syndrome.

Bronchial wall thickening is a common finding on children's X-rays

Look for "tram track" parallel lines around the hilar

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The usual causes are viral infection or asthma but this is a common finding

with cystic fibrosis. Heart and mediastinum

The anterior mediastinum, in front of the heart, contains the thymus gland

It appears largest at about 2 years old but it continues to grow into

adolescence. It grows less fast than the rest of the body and so becomes

relatively smaller

The right lobe of the lung can rest on the horizontal fissure, which is often

called the sail sign.

Assessment of the heart includes assessment of size, shape, position and

pulmonary circulation

The cardiothoracic ratio is usually about 50% but can be more in the first

year of life and a large thymus can make assessment difficult, as will a film

in poor inspiration.

As with adults, one third should be to the left of centre and two thirds to the

right. Assessment of pulmonary circulation can be important in congenital

heart disease but can be very difficult in practice.

2) Bronchoscopy

3) Blood Gas analysis

This is analysis of the oxygen and carbon dioxide levels in the blood

4) Total Blood count

Shows the various red blood cell indices, white blood cells (total and

differential count) and the platelets

5) Sputum Examination

Refer to earlier class

discussions

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6) Blood cultures

Done to determine the microbes present and their sensitivity to various

drug agents (details in microbiology)

7) Peak Expiratory Flow

The purpose is to measure lung function

The patient inhales deeply and exhales hard into a plastic tube in order to

get a reading for how fast the patient is able to exhale successfully

The result of this test is a peak flow number.

8) Spirometry

Is a non-invasive method of lung function testing, which measures the

amount (volume) and/or speed (flow) of air that can be inhaled and

exhaled

A spirometer is a device used

Indications

i) To determine how well the lungs receive, hold, and utilize air

ii) To monitor a lung disease

iii) To monitor the effectiveness of treatment

iv) To determine the severity of a lung disease

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v) To determine whether the lung disease is restrictive (decreased

airflow) or obstructive (disruption of airflow)

After taking a deep breath, a person forcefully breathes out into the

spirometer as completely and forcefully as possible. The spirometer

measures both the amount of air expelled and how quickly the air was

expelled from the lungs. The measurements are recorded by the

spirometer

The normal, healthy values measured by the spirometer for the amount of

air exhaled vary from person to person. The results are compared to the

average expected in someone of the same age, height, sex, and race,

Values below 80 percent of the average, it may be a sign of lung disease or

other airflow obstruction.

9) ECG

10) Ultrasound

11) CT Scan

12) MRI

13) Biopsy

What are the indications of a biopsy?

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Lesson 2: Paediatric Lung Disease Learning Outcomes

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

1. Discuss the developmental anomalies of the respiratory system

2. Describe the causes and effects of acute respiratory distress syndrome

(hyaline membrane 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), bronchogenic cysts; 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 oligohydromnious

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

anencephaly.

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

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5.0 Neonatal Respiratory Distress Syndrome (Hyaline

Membrane Disease) Introduction

Occurs due to deficiency of surfactant and primarily disease of premature

infants

Seen in infants of diabetic mothers (excess insulin production by the foetus

suppresses surfactant production)

Neonates born at the gestation 32 – 36 weeks have 20% mortality while those

at < 28 weeks have 60% mortality

The risk factors include prematurity, diabetic mother, neonatal aspiration

and 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

Diagram 2.1: Pathogenesis of ARDS

ARDS results from widespread acute injury to the alveolar capillary

membrane, which produces high permeability oedema and inhibits

surfactant function (especially fibrin monomers)

Epithelial injury also impairs new surfactant synthesis and inflammation may

exacerbate the injury because of release of oxidants and lysosomal

enzymes from activated leukocytes

Lack of surfactant results in lung collapse with microatelectasis.

Hypoxia causes damage to the alveolar lining cells and pulmonary arterial

constriction resulting in endothelial damage hence plasma leaks into the

alveoli where it is deposited as fibrin (bright pink-stained membrane) and

thus the name hyaline membrane disease. Fibrin reduces gas exchange

further worsening the hypoxic state.

RISK FACTORS

Prematurity (<

36 weeks)

Lung Collapse

Multiple

Pregnancy

Caesarean

Section

Maternal

Diabetes

Amniotic Fluid

aspiration

Low Level surfactant

Hypoxia Pulmonary Vasoconstriction

FIBRIN/HYALINE Membrane

Endothelial Damage Alveolar Lining damage

IMMATURE/DAMAGED TYPE II PNEUMOCYTES

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Lung compliance is decreased because many airspaces contain oedema

(and hence cannot accept air) and because abnormally high surface

tension counteracts the negative intrapleural pressure. Pathology

The lungs: -

1. Have fibrous obliteration of bronchioles

2. Peribronchial fibrosis

3. Overdistended alveolar

Clinical Features

Dyspnoea

Tachypnoea (faster than 60 breaths a minute

Makes a grunting sound when he breathes out

Has respiratory distress (what are the features)

Cyanosis

Crepitations

Diagnosis

1) Blood culture - check for infection

2) Blood gas analysis - check amount of oxygen in blood

3) Chest X-ray

Differential Diagnosis

Complications

1. Intracerebral bleed ( hypoxia related)

2. PDA (failure to close as normal closure is stimulated by oxygenation)

3. Necrotizing enterocolitis ( ischaemic/hypoxic damage of the gut)

4. Bronchopulmonary dysplasia (high pressure ventilation and oxygen toxicity

to alveolar lining cells)

What are the differential diagnoses?

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Lesson 3: Upper Respiratory Tract Disorders Learning Outcomes

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

1. Discuss the pathology of conditions affecting organs of the upper

respiratory tract

A. EPISTAXIS

Epistaxis is common affecting 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. 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 super infection.

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.

Because 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 histopathology includes -

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 because of chronic recurrent inflammation of the nasal

mucosa particularly of allergic aetiology that result in polypoid thickening of

the mucosa. Polyps are rounded or elongated masses that are usually bilateral

with gelatinous consistency and smooth and shiny surface.

Diagram 3.1: Nasal Polyps

D. THE LARYNX AND TRACHEA 1. Acute Laryngitis and Tracheaitis

Acute laryngitis and tracheaitis are common occurrences

Aetiology

1. Viral - Adeno virus;Epstein Barr virus (EBV)

2. Bacteria - Strep. Pneumonia, Strep. Pyogenes, Neisseria catarrhalis,

Heamophilus influenzae and Corynebacterium diptheriae

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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 because of streptococcal infection while Heamophilus

influenza type B usually causes acute epiglottitis, which is a childhood illness.

Chronic Laryngitis

Frequently associated with excessive, smoking, repeated attacks of infection

and atmospheric pollution.

TB 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.

E. UPPER AIRWAY OBSTRUCTION

Upper airway obstruction is one of the most serious emergencies faced by

clinicians

Early diagnosis followed by restoration of airflow is essential to prevent

cardiac arrest or irreversible brain damage that occurs within minutes of

complete airway obstruction

May be functional or anatomic and may develop acutely or subacutely

Occurs at any level of the upper respiratory tract but laryngeal obstruction

has a particular importance because the larynx is the narrowest portion of

the upper airway.

Causes

1) Traumatic causes

Laryngeal stenosis; airway burn; acute laryngeal injury; facial trauma

(mandibular or maxillary fractures); haemorrhage

2) Infections - suppurative parotitis; retropharyngeal abscess; tonsillar

hypertrophy; Ludwig’s angina; epiglottitis; laryngitis.;

Laryngotracheobronchitis (croup); Diphtheria

3) Iatrogenic causes

a) Tracheal stenosis post-tracheostomy

b) Tracheal stenosis post-intubation

c) Mucous ball from transtracheal catheter

4) Foreign bodies

5) Vocal cord paralysis

6) Tumours

a) Laryngeal tumours (benign or malignant)

b) Laryngeal papillomatosis

c) Tracheal stenosis (caused by intrinsic or extrinsic tumours)

7) Angioedema

Page 20 Carey Francis Okinda

a) Anaphylactic reactions

b) Angiotensin-converting enzyme inhibitors Clinical Features

Marked respiratory distress; altered voice; dysphagia; odynophagia; the

hand-to-the-throat choking sign; stridor; facial swelling; prominence of

neck veins; absence of air entry into the chest; tachycardia

In an unconscious or sedated patient, the first sign of airway obstruction

may be inability to ventilate with a bag-valve mask after an attempt to

open the airway with a jaw-thrust maneuver

Asphyxiation progresses; cyanosis; bradycardia; hypotension; irreversible

cardiovascular collapse

Investigations

1) Plain Chest and Neck Radiographs

2) Computed Tomography

3) Spirometry

4) Bronchoscopy

F. 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

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?

7. Management

Page 21 Carey Francis Okinda

Lesson 4: Respiratory Failure & Atelectasis (Lung Collapse)

Learning Outcomes

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

1. Describe the causes of lung collapse

2. Discuss the effects and features of lung collapse

3. Describe causes and effects of lung collapse

4. Discuss the pathophysiology and complications of lung collapse

5. 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

PaCO2 is 4.7kPa – 6.0 kPa (35 – 45 mmHg)

Respiratory failure is defined as when PaO2 falls below 8 kPa (60 mmHg).

Respiratory failure is a syndrome of inadequate gas exchange due to

dysfunction of one or more essential components of the respiratory system

namely chest wall, airways, alveolar–c capillary units, pulmonary

circulation, nerves and CNS/brain Stem

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

3.0 PREDISPOSING FACTORS

1. Infection in the tracheobronchial tree, pneumonia, fever

2. Change in tracheobronchial secretions (increased volume and

viscosity)

3. Bronchospasms

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

Page 22 Carey Francis Okinda

4. Disturbance in ability to clear secretions

5. Drugs – sedatives, narcotics, anaesthetics

6. Oxygen therapy

7. Trauma

8. Cardiovascular disorders

9. Pneumothorax

4.0 CAUSES

1. Extrinsic Lung Disorders

a. Respiratory centre depression e.g. Drug overdose (sedatives,

narcotics); cerebral trauma or infarction; bulbar poliomyelitis and

encephalitis

b. Neuromuscular disorders - cervical cord injury; Guillain-Barre

Syndrome; myasthenia gravis and muscular dystrophy

c. Pleural and chest wall disorders e.g. chest injury (flail chest, rib

fracture); pneumothorax; pleural effusion; kyphoscoliosis (abnormal

lung) and obesity – Pickwickian syndrome

2. Intrinsic Lung Disorders

a. Diffuse obstructive disorders e.g. emphysema and chronic bronchitis

(COPD); asthma and status asthmaticus and cystic fibrosis

b. Diffuse restrictive disorders e.g. Interstitial fibrosis e.g. silica and coal;

pulmonary oedema (cardiogenic, non-cardiogenic e.g. ARDS);

atelectasis ; consolidated pneumonia

c. pulmonary vascular disorders e.g. pulmonary emboli and severe

emphysema

5.0 CLASSIFICATION

1. Type I – Failure of oxygen exchange (PaO2 <60)

2. Type II – Failure to exchange or remove carbon dioxide (PaCO2 >45)

1. Type III – Post operative respiratory failure (both oxygen and

ventilatory failure)

2. Type IV – Shock

5.1. Type I Respiratory Failure

Is a state of hypoxaemia without CO2 retention (blood carbon dioxide

remains within the normal limits)

Failure of oxygen exchange

Pathophysiologic mechanisms of arterial hypoxaemia include

1) Decreased partial pressure of O2 in alveoli

a) Hypoventilation

b) Decreased partial pressure of O2 in the inspired air

c) Underventilated alveoli (areas of low ventilationperfusion)

2) Intrapulmonary shunt (areas of zero ventilation-perfusion)

3) Decreased mixed venous O2 content (low-haemoglobin saturation)

a) Increased metabolic rate

b) Decreased cardiac output

c) Decreased arterial O2 content

Page 23 Carey Francis Okinda

Causes

1. Adult respiratory distress syndrome (ARDS)

2. Asthma

3. Pulmonary oedema

4. Chronic obstructive pulmonary disease (COPD)

5. Interstitial fibrosis

6. Pneumonia

7. Pneumothorax

8. Atelectasis

Diagnosis

1. Arterial blood gases analysis – reduced PaCO2

2. Respiratory function tests – reduced FEVR and FEV1

5.2. Type II Respiratory Failure

Failure to exchange or remove carbon dioxide

A state of decreased PaO2 and increased PaCO2 (> 6.7 kPa/50 mmHg)

Results from alveolar hypoventilation and is commonly from chronic

bronchitis and emphysema

Causes

1) Disorders affecting central ventilatory drive

a) Brain stem infarction or haemorrhage

b) Brain stem compression from supratentorial mass

c) Drug overdose, narcotics, benzodiazepines, anaesthetic agents etc.

2) Disorders affecting signal transmission to the respiratory muscles

a) Myasthenia Gravis

b) Gullain-Barrè syndrome

c) Spinal –Cord injury and Head injury

d) Multiple sclerosis

e) Residual paralysis (Muscle relaxants)

3) Disorders of respiratory muscles or chest-wall

a) Muscular dystrophy

b) Polymyositis

c) Flail Chest

d) Thoracic wall deformities

Mechanism

Reduced alveolar ventilation results in reduced ventilator effort and there is

inability of the alveolar to overcome increased resistance to ventilation.

5.3. Type III Respiratory Failure

Perioperative respiratory failure

Increased atelectasis due to low functional residual capacity (FRC) in the

setting of abnormal abdominal wall mechanics

Page 24 Carey Francis Okinda

Often results in type I or type II respiratory failure and can be enhanced by

anaesthetic or operative technique, posture, incentive spirometry, post-

operative analgesia, attempts to lower intra- abdominal pressure

Causes

1. Inadequate post- operative analgesia, upper abdominal incision

2. Obesity, ascites

3. Pre- operative tobacco smoking

4. Excessive airway secretions

5. Adult ARDS

6. Asthma

7. Chronic obstructive pulmonary disease

5.4. Type IV Respiratory Failure

Describes patients who are intubated and ventilated in the process of

resuscitation for shock

Goal of ventilation is to stabilize gas exchange and to unload

Causes

1. Cardiogenic shock

2. Septic shock

3. Hypovolemic shock

6.0 EFFECTS ON CVS

Chronic respiratory failure has major effects in the cardiovascular system

including pulmonary hypertension and polycythaemia.

Pulmonary Hypertension

Pulmonary vasoconstriction results in increased pulmonary artery pressure

and increased work of the ventricles

The effects are 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.

7.0 FEATURES OF RESPIRATORY FAILURE

Tachycardia, tachypnoea, sweating, inability to speak

Use of accessory muscles of respiration

Pulsus paradoxical and 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

8.0 INVESTIGATIONS

1) Chest x-ray

2) ECG

3) Echocardiogram

Page 25 Carey Francis Okinda

4) Pulmonary function tests

5) Bronchoscopy

6) Blood gas analysis

Collapse of Lung Tissue – Atelectasis 1.0 INTRODUCTION

Lung collapse comprises of atelectasis and acquired collapse

‘Atelectasis’ is a Greek word for imperfect expansion Atelectasis refers to incomplete expansion of the lungs (neonatal

atelectasis) or the collapse of a previously inflated lung (acquired

atelectasis) encountered in adults.

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).

Diagram 4.1: Lung Collapse

2.0 ATELECTASIS (Neonatal)

Atelectasis is incomplete expansion of neonatal lung (failure of lungs to expand

at birth).

Aetiology

1. Failure of the respiratory centre

2. Prematurity – lack of surfactant, immaturity of the respiratory centre

3. Hyaline membrane disease

4. Laryngeal dysfunction

5. Obstruction of airway passages

6. Idiopathic

7. Cerebral damage – depresses respiration

Page 26 Carey Francis Okinda

3.0 ACQUIRED LUNG COLLAPSE

Can occur because of resorption atelectasis, compression atelectasis and

contraction 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

Seen in bronchial asthma, chronic bronchitis, bronchiectasis, post-

operative states and aspiration of foreign bodies

Secretions then replace the air and oedema fluid, which become infected

quite easily resulting suppuration and tissue destruction that results in

irreversible pulmonary fibrosis.

Diagram 3.2: Resorption

Compression Atelectasis

Occurs when pleural cavity is partially or completely filled with fluid

exudates; tumours blood or air e.g. pneumothorax and tension

pneumothorax

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

Page 27 Carey Francis Okinda

Diagram 4.3: Compression Atelectasis

Causes

1. Pleural effusion

2. Haemothorax

3. Empyema

4. Pneumothorax

5. Haemo-pneumothorax

Contraction Atelectasis

Occurs when local or generalized fibrotic changes in the lungs/pleural

cavity prevent full expansion of the lung.

Diagram 4.4: Contraction Atelectasis

CLINICAL TASK

1. What are the clinical features of lung

collapse?

2. What investigations will be important?

3. What are the differentials?

Page 28 Carey Francis Okinda

Left Side Collapse

Upper Lobe Collapsed

Page 29 Carey Francis Okinda

Lesson 5: 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 and emphysema

2. Diagnose bronchial obstruction and emphysema

3. Investigate bronchial obstruction and emphysema

Obstructive Pulmonary Diseases

The bronchi have ciliated mucous secreting cells that defend the airways

and lungs against bacteria and foreign bodies

Chronic irritation of the bronchi leads to hyperplasia and hypertrophy of the

mucous secreting glands and goblet cells

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 bronchial obstruction have limitations of maximal airflow rates

during forced expiration at 1 second (reduced FEV1).

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.

Key aetiological factors in COPD are smoking (major risk), environmental

pollutants (e.g. occupation – mines, dust) andantitrypsin deficiency.

Table 1: Disorders of Airflow Obstruction Clinical

Term

Anatomic

site

Major Pathologic

changes

Aetiology Signs/symptoms

Chronic

Bronchitis

Bronchus Mucous gland

hyperplasia and

hypersecretion

Tobacco smoke

and pollutants

Cough and

sputum

production

Bronchiectasis Bronchus Airway dilatation and

scarring

Persistent or

severe infections

Cough, purulent

sputum and fever

Asthma Bronchus Smooth muscle

hyperplasia, excess

mucous and

inflammation

Immunologic or

undefined causes

Episodic

wheezing, cough

and dyspnoea

Emphysema Acinus Airspace enlargement

and wall destruction

Tobacco smoke Dyspnoea

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

Page 30 Carey Francis Okinda

Secondary bacterial infection ensues producing suppurative bronchitis and

by extension suppurative bronchopneumonia.

1.0 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

2.0 EFFECTS

1. Lung collapse - complete obstruction of the bronchioles leads to absorption

of the air in the alveoli with the alveolar spaces collapsing.

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

EMPHYSEMA

Emphysema is abnormal permanent dilatation/enlargement of airspaces

distal to the terminal bronchiole accompanied by destruction of the

bronchiole walls without fibrosis

It is a constituent of COPD/COAD

Diagram 5.1: Emphysema

Page 31 Carey Francis Okinda

1.0 AETIOLOGY

The main factors are -

1. Smoking – major risk factor that is dose related

2. -antitrypsin deficiency – a protease inhibitor that prevents lung damage

especially in smokers

3. Occupation – dusty environments e.g. coal mines

2.0 PATHOGENESIS

Is due to imbalance between protease and anti-protease activities in the

lung resulting in destruction of the alveolar walls (Anti-protease hypothesis)

o -antitrypsin 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

o Deficiency of-antitrypsin occurs in homozygous states however in

smoking accelerates the damage in heterozygous situations

Smoking

o Reduces anti-elastase and increases elastolytic protease in the lungs due

to oxidants in cigarette smoke which inhibit -antitrypsin and smokers

have increased phagocytes and neutrophils in the lungs

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

Diagram 5.2: Pathogenesis of Emphysema

3.0 PATHOLOGY

Macroscopy

Voluminous pale lungs with dilatation of air spaces

Microscopy

Dilatation of air spaces

Destruction of septal wall resulting in thin walls

Compressed capillaries

Rupture of walls producing honeycombs

Smoking

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

Neutrophils and macrophages

release elastase

Elastases destroy alveolar wall

Emphysema

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

Page 32 Carey Francis Okinda

4.0 CLASSIFICATION

Classification is based on anatomical distribution within the lobule.

a) Centrilobular/centriacinar

b) Panaacinar/panlobular

c) Paraseptal/distal acinar

d) Irregular

4.1. 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).

Distal acinar are spared

Associated with cigarette smoking, chronic bronchitis and inflammation of

distal airways

4.2. Panacinar (Panlobular) Emphysema

Affects all acinar which are uniformly enlarged from the level of the

respiratory bronchioles to the terminal blind alveoli

Associated with 1-antitrypsin deficiency

4.3. 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

4.4. Irregular Emphysema

Acinar irregularly affected

Mainly associated with scarring

Most common form of emphysema

5.0 CLINICAL FEATURES

Cough, expectoration; wheezing; slowly increasing severe exertional

dyspnoea; respiratory distress; chest – barrel shaped; hyper-resonant

percussion note; hyperventilation; tachycardia; patients are “pink puffers” –

they remain well oxygenated and have tachycardia; do not tolerate, hypoxia;

Weight loss

6.0 COMPLICATIONS

1) Cor pulmonale

2) Congestive Cardiac failure

3) Pulmonary hypertension

TASK

Compare and contrast emphysema and

chronic bronchitis.

State the important investigations

Page 33 Carey Francis Okinda

Lesson 6: Bronchiectasis, Bronchitis and Bronchiolitis

Learning Outcomes

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

1. Describe causes and effects of bronchiectasis, bronchitis and bronchiolitis

2. Diagnose bronchiectasis, bronchitis and bronchiolitis

3. Investigate bronchiectasis, bronchitis and bronchiolitis

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 infections

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.

Diagram 6.1: Bronchiectasis

2.0 AETIOLOGY

The main categories: -

1. Pulmonary infection

2. Bronchial obstruction

Page 34 Carey Francis Okinda

3. Associated factors

a. Congenital and hereditary conditions e.g. Cystic fibrosis; Intralobular

sequestration of the lung; Immunodeficiency states; Kartagener’s

syndrome (Bronchiectasis, sinusitis, displacement of viscera (heart) –

immobility of the cilia; Congenital bronchiectasis; atelectasis

b. Post infection conditions e.g. Necrotising pneumonia caused by bacteria

(Myocobacterium tuberculosis, Staphylococcus aureus, Haemophilus

influenza and Pseudomonas), viral (HIV, adenoviruses and influenzae),

fungal (Aspergillus)

c. Bronchial obstruction e.g. tumours, foreign bodies and mucous

impaction

d. Others e.g. Bronchiolitis and bronchopneumonia in childhood;

Rheumatoid arthritis; S.L.E; Inflammatory bowel syndrome; post-

transplant

3.0 PATHOGENESIS

The major factors in the pathogenesis of bronchiectasis are obstruction and

infection.

Diagram 6.2: Pathogenesis of Bronchiectasis

3.1. Obstruction

Obstruction leads to accumulation and stagnation of secretions

Secretion later become infected resulting in an inflammatory reaction that

leads to destruction and weakening of the bronchial walls facilitating

dilatation of the bronchi.

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.

Page 35 Carey Francis Okinda

Cavities formed accommodate a lot of secretion within the bronchi, which

become infected becoming purulent

Without treatment of the infection, the fluid trapped within cavities becomes

infected persistently 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).

Diagram 6.3: Pathogenesis - Obstruction

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.

3.2 Infections

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 that allows accumulation and stagnation of the

secretions that easily become secondarily infected causing further damage

of the bronchial wall. Microorganisms associated with this phenomenon are

bacterial infection with

Mycobacterium tuberculosis, Heamophilus influenzae, Staphylococcus and

fibrosing, suppurative pneumonias and corrosive chemicals. Infection may

be primary infection of secondary to local obstruction and impaired

systemic defence systems.

Repeated infections results in increased damage to the airway walls with

destruction of the supporting smooth muscle and elastic tissues 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)

Page 36 Carey Francis Okinda

Diagram 6.4: Pathogenesis – Infections

4.0 PATHOLOGY

Macroscopy

1. Dilated bronchi with thickened walls

2. Lumen filled with mucous or muco-pus

3. Firbrotic surrounding lung

4. Dilatation Microscopic

1. Epithelium - normal, ulcerated or squamous epithelium

2. Bronchial wall - infiltrated by acute and chronic inflammatory cells,

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

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

What is the relationship

between Bronchiectasis and cystic fibrosis?

Page 37 Carey Francis Okinda

7.0 EFFECTS/COMPLICATIONS

1) Suppuration/empyema

2) Septic emboli (Brain abscess)

3) Pyaemia - brain abscess (metastatic) and meningitis – from involvement

of the pulmonary vein

4) Finger clubbing (Hypertrophic pulmonary osteodystrophy)

5) Pulmonary hypertension

6) Cor pulmonalae

7) Amyloidosis

8) COPD

9) Recurrent pneumonia

10) Respiratory failure

BRONCHITIS

1.0 Acute Bronchitis

This is inflammation of the large and medium bronchi.

1.1. Aetiology

1. Viral - respiratory syncytial virus; rhinovirus; echovirus; parainfluenza types

1, 2 3; Influenza, Herpes viruses, Coxsackie viruses, Corona viruses,

Adenoviruses and Measles

2. Mycoplasma - Candida albicans, Candida tropicalis, Histoplasma capsulatum

and Cryptococcus neoferans

3. Bacteria (secondary infection) - Strep pneumonia, H. Influeanzae, Strep

pyogenes (common in infants, ), Staph aureus (common in infants) and

Salmonella typhi

Diagram 6.5: Bronchitis

Page 38 Carey Francis Okinda

1.2. Pathogenesis

Invasion by microbes 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.

Spread of the inflammatory reaction to involve 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. 1.3. Pathology

Macroscopy

Congested, swollen/oedematous, hyperaemia and tenacious mucous

exudate, sputum – yellow/green

Microscopy

Congested mucosa with infiltration by neutrophils 1.4. Clinical Features

Cough – initially unproductive but later yellow/green sputum.

Wheezes/rhonchi, crepitations

Shortness of breath

Fever

Neutrophilia

2.0 Chronic Bronchitis

2.1. Introduction

Chronic bronchitis is defined clinically as persistent cough with sputum

production on most days for at least 3 months in at least two consecutive

years

It is not primarily an inflammatory condition but consists of metaplastic

changes as a result of chronic irritation of the bronchial epithelium.

2.2. 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 and predispose to acute exacerbations of chronic bronchitis

5. Familial/genetic factors - poorly understood

Page 39 Carey Francis Okinda

2.3. Pathogenesis

Chronic irritation of the bronchial epithelial cells causes hypertrophy and

hyperplasia of the mucous glands leading to excessive secretion of mucous

secretions(more goblet cells than ciliated cells)

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 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.

Diagram 6.6: Evolution of Chronic Bronchitis

2.4. Pathophysiology

Mucous hypersecretion is a physiological response to inhaled irritants

Increased secretion impairs normal clearance

Impaired cilia function and increased accumulation of mucous secretions

Increased susceptibility to acute respiratory infections with bacterial -

suppuration.

2.5. Pathology

Macroscopy

Hyperaemia and oedema of mucous membrane

Mucous secretions and increased size of mucous glands

Plugging of bronchi and bronchioles

Fibrosis and inflammatory changes

Microscopy

Venous congestion

Metaplasia, hypertrophy and dysplasia

Inflammatory cells

Bronchiolar and Bronchial injury

Bronchospasms

Infections Hyper secretion of mucous

Reversible obstruction in bronchioles and small bronchi

Chronic Bronchitis

Continued and repeated infections

Continued and repeated injury (e.g. smoking)

Page 40 Carey Francis Okinda

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.)

2.6. Differential Diagnosis

1. Bronchial asthma

2. Emphysema

3. COPD

4. Bronchiectasis

5. Chronic pulmonary infections

6. Chronic sinusitis with post-nasal drip

2.7. Complications

1. Respiratory failure

2. Emphysema

BRONCHIOLITIS 1.0 INTRODUCTION

Bronchiolitis is inflammation of small, intralobular bronchi and bronchioles

seen in children, old people and debilitated states.

Bronchiolitis is a lower respiratory tract infection usually caused by a virus

and occurs in children younger than two years old

It is fatal as organisms spread to adjacent acini resulting in

bronchopneumonia

It is usually caused by a virus which causes inflammation of the small airways

(bronchioles) partially or completely blocking the airways resulting in

wheezing. Less oxygen enters the lungs, potentially causing a decrease in

the blood level of oxygen.

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).

Breast-feeding is considered protective and should be encouraged. Breast

milk with colostrum rich has high levels of immunoglobulin A (IgA)

Infants are affected most often because of their small airways, high closing

volumes, and insufficient collateral ventilation

2.0 CAUSES

Respiratory syncytial virus (RSV) – most common cause

Human metapneumovirus (hMPV) - second most common cause

Adenovirus - occasionally causes a similar syndrome with a more virulent

course

Parainfluenza virus

Other less common causes include Mycoplasma pneumonia, Enterovirus,

Influenza virus, Rhinovirus, Chlamydophila pneumoniae

Page 41 Carey Francis Okinda

3.0 RISK FACTORS

1. Low birth weight, particularly premature infants

2. Gestational age (independently associated with hospital resource use

and outcome among infants hospitalized for RSV infection)

3. Lower socioeconomic group

4. Crowded living conditions, day-care, or both

5. Parental smoking

6. Chronic lung disease,

7. Severe congenital or acquired neurologic disease

8. Congenital heart disease (CHD) with pulmonary hypertension

9. Congenital or acquired immune deficiency diseases

10. Age less than 3 months

11. Airway anomalies

4.0 PATHOPHYSIOLOGY

Bronchioles are small airways (< 2 mm in diameter), lack cartilage, and

submucosal glands. The terminal bronchiole, a 16th-generation airway, is

the final conducting airway that terminates in the respiratory bronchioles.

The acinus (gas exchange unit) consists of respiratory bronchioles, the

alveolar duct, and alveoli

The bronchiolar lining consists of surfactant-secreting clara cells and

neuroendocrine cells, which are the source of bioactive products such as

somatostatin, endothelin, and serotonin.

Mechanisms

1. Bronchiolar injury and the consequent interplay between inflammatory

and mesenchymal cells can lead to diverse pathologic and clinical

syndromes. Effects of bronchiolar injury include:

a. Increased mucus secretion

b. Bronchial obstruction and constriction

c. Alveolar cell death, mucus debris, viral invasion

d. Air trapping

e. Atelectasis

f. Reduced ventilation that leads to ventilation-perfusion mismatch

g. Laboured breathing

2. Complex immunologic mechanisms - Type 1 allergic reactions mediated

by immunoglobulin E (IgE) may account for some clinically significant

bronchiolitis.

3. Necrosis of the respiratory epithelium and epithelial regeneration with

non-ciliated cells impairs elimination of secretions.

4. Proliferation of goblet cells results in excessive mucus production

5. Cytokines and chemokines - released by infected respiratory epithelial

cells, amplify the immune response

6. Airway obstruction was due to epithelial and inflammatory cell debris

mixed with fibrin, mucus, and oedema fluid but not to bronchial smooth

muscle constriction

Page 42 Carey Francis Okinda

5.0 CLINICAL FEATURES

Symptoms

Early symptoms are those of a viral URTI, including mild rhinorrhoea,

cough and fever. Fever >39°C

Paroxysmal cough and dyspnoea develop within 1-2 days.

Wheeze, cyanosis, vomiting, irritability and poor feeding

Signs

Look for tachypnoea, tachycardia, fever, cyanosis and signs of

dehydration. It is unusual for a child to appear 'toxic' (suggested by

drowsiness, lethargy, pallor, mottled skin)

Mild conjunctivitis, pharyngitis.

Evidence of increased respiratory work: intercostal, subcostal and

supraclavicular recession, nasal flaring.

Widespread fine inspiratory crackles, high-pitched expiratory wheezing

Liver and spleen may be palpable due to hyperinflation of the lungs.

Diagram 6.7: Features of Bronchiolitis

6.0 PATHOLOGY

Virus-induced inflammation of the bronchiolar epithelium, with

hypersecretion of mucus and oedema of the surrounding submucosa

These changes result in formation of mucous plugs obstructing bronchioles

with consequent hyperinflation or collapse of the distal lung tissue

Resistance in small air passages is increased during inspiration and

expiration, but because airway radius is smaller during expiration,

resultant ball valve respiratory obstruction leads to early air trapping and

overinflation

Atelectasis may occur when obstruction becomes complete and trapped

air is absorbed

Page 43 Carey Francis Okinda

Diagnosis and Grading

Feature Mild Moderate Severe

Wheeze

None or end

expiratory

Entire expiration

Inspiratory & Expiratory

Feeding Normal

Less than usual. Frequently

stops feeding.

More than ½ normal feeds.

Not interested.

Gasping / coughing.

Less than ½ normal feeds

Oxygen No oxygen

requirement

May require oxygen Requires oxygen

In

drawing No / mild

in drawing

Intercostal and / or

tracheosternal

Severe with nasal flaring

Behaviour Normal Some/intermittent irritability Irritability and/or lethargy

7.0 DIFFERENTIAL DIAGNOSIS

1. Asthma

2. Bronchitis

3. Pulmonary oedema

4. Foreign body inhalation

5. Pneumonia

6. Aspiration

7. Cystic fibrosis

8. Pneumothorax

8.0 INVESTIGATIONS

1. Pulse oximetry

2. Nasopharyngeal aspirate for viral cultures for RSV, influenza A and B,

parainfluenza and adenovirus

3. CXR

a. Children with a clear clinical diagnosis of bronchiolitis do not require a

chest x-ray.

b. Show signs of hyperinflation, peribronchial thickening, and often-patchy

areas of consolidation and collapse

4. Full Blood Count

5. Electrolytes and renal function

6. Blood and urine culture: consider if pyrexia >38.5°C or the child has a

'toxic' appearance.

7. Arterial blood gases: may be required in the severely ill patients,

especially in those who may need mechanical ventilation.

9.0 COMPLICATIONS

Cyanosis

Dehydration: when the normal water content of the body is reduced

Fatigue: extreme tiredness and a lack of energy

Severe respiratory failure: an inability to breathe unaided

Pneumonia

Atelectasis

Pleural effusion

Page 44 Carey Francis Okinda

Lesson 7: Bronchial Asthma

Learning Outcomes

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

1) Discuss the causes , pathogenesis and pathophysiology of asthma

2) Investigate a patient with asthma

3) 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.

Asthmatic attacks cause shortness of breath and wheezing respirations

because of restricted movement of air through tightly constricted air

passages

Bronchial spasms exert great effect on expiration than inspiration because

the calibre of bronchioles varies with the phase of respiration.

Diagram 7.1: Anatomical Considerations in Asthma

Page 45 Carey Francis Okinda

2.0 AETIOLOGY

Unclear but associations exist with genetic makeup, atopy or allergy and

increased responsiveness of the airways

Precipitants include occupational sensitises, allergens, infections and non-

specific e.g. cold air, exercise, diet, atmospheric pollution/irritants, dust,

vapours, fumes, emotion, drugs e.g. NSAIDS

3.0 AETIOLOGICAL 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

Diagram 7.2: Progression in Asthma

Hypersensitivity

Hypersensitive airway disease

Bronchitis

Asthma (overt)

3.1. Extrinsic (Atopic, Allergic) Asthma

Commonest type of asthma that has a definite cause associated with the

disease as it runs in families and individuals with history of allergy

Individuals may have a history of diseases such as rhinitis, urticaria and

infantile eczema. Atopic or extrinsic asthma begins in childhood and early

adult life

Subjects with extrinsic asthma have increased levels of IgE representing

type I hypersensitivity reaction mechanisms and they do show characteristic

wealing skin reactions to common allergens in the environment.

Pathogenesis

Exposure of pre-sensitized IgE coated mast cells to allergens (antigens)

results in release of chemical mediators in a reaction that first takes place

on the mucosal surface and results in the opening of the intercellular tight

junctions thereby enhancing penetration of the mast cells by antigens to

reach the numerous submuocal mast cells.

Direct stimulation of the subepithelial vagal (parasympathetic) receptors

provokes bronchoconstriction through both central and local reflexes.

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

severe cases).

Mast cells release cytokines, which result in influx of leucocytes (neutrophils, monocytes, lymphocytes, basophils and oesinophils)

which mediate the late phase reaction together with recruited chemotaxic

factors.

Page 46 Carey Francis Okinda

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 7.3: Pathogenesis

3.2. Intrinsic Asthma (Non-atopic)

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 bronchoconstritive leukotrienes.

3.4. Exercise Induced

Is a phenomenon that can occur in isolation or in association with any type

of asthma

Many patients experience airway obstruction, 5 to 20 minutes after

completing the exercise or in the course of it, by a mechanism that seems to

Page 47 Carey Francis Okinda

include the cooling, the relative dryness of the airway secondary to

increased ventilation and loss heat the air.

The precise pathophysiology remains unclear, but may involve heat and

water loss from the airway

The osmotic hypothesis proposes that this water loss leads to dehydration

and hyperosmolarity of the airway surface liquid causing the release of

water from airway cells. This water loss results in cell shrinkage, vascular

leak and the release of mediators, which cause airway smooth muscle

contraction, edema, and bronchoconstriction. This shift in water from the

cells and the subsequent regulatory volume increase most likely involve

alterations in ion channels and signalling pathways

The thermal hypothesis proposes that the rapid rewarming of the airway

following heat loss during exercise is associated with a reactive hyperemia

of the bronchial vasculature, which results in congestion of the vascular bed

and airway obstruction.

3.5. Occupational Asthma

Occupational asthma is stimulated by fumes (epoxy resin, plastics), organic

and chemical dusts (wood, cotton, platinum), gases (toluene), chemicals

(formaldehyde and penicillin products).

4.0 PATHOGENESIS AND PATHOPHYSIOLOGY

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

inflammation and airway obstruction

4.1. Airway Hypersensitivity (hyperesponsiveness)

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

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 and oedema

Following the hypersensitivity reaction and release of mediators of

inflammation, there ensues an inflammatory reaction that results in oedema

formation, bronchoconstriction and hypersecretion of mucous and

accumulation of oesinophils and neutrophils. There is infiltration of the

airways with inflammatory cells, Thelper lymphocytes, oesinophils and mast

cells, which is a common feature in asthma.

Page 48 Carey Francis Okinda

4.3. Airway Obstruction/bronchoconstriction

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. Airway remodelling

In some patients permanent structural changes can occur in the airway

The changes are associated with a progressive loss of lung function that is

not prevented by or fully reversible by current therapy

Airway remodelling involves an activation of many of the structural cells,

with consequent permanent changes in the airway that increase airflow

obstruction and airway responsiveness and render the patient less

responsive to therapy

The changes can include thickening of the sub-basement membrane,

subepithelial fibrosis, airway smooth muscle hypertrophy and hyperplasia,

blood vessel proliferation and dilation, and mucous gland hyperplasia and

hyper secretion

4.5. Cells Involved

Mast Cells

The number is increased in the respiratory epithelium and surface

secretions

They cells generate and release powerful smooth muscle and vasoactive

mediators such as histamine, prostaglandin D2 (PD2) and leukotrienes C4

(LTC4) that cause the immediate asthmatic reaction. Note that 2

adrenoreceptor e.g. salbutamol inhibit release of mediators by the mast

cells.

The Epithelium

Shed during exacerbations of asthma resulting in desquamations, which

increase permeability of the airway to inhaled allergens and exposure of

nerve fibre endings

Desquamated materials from the columnar epithelium can be identified in

the sputum as twisted strips called Curschmann’s spirals

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.

Inflammatory Cells

i). Macrophages and Lymphocytes - are abundant in the mucous membranes

of the airways and alveoli.

ii). Oesinophils - are abundant in bronchial secretions and when activated they

release mediators such as PAF and LTC4, major basic protein (MBP) and

Page 49 Carey Francis Okinda

eosinophil cationic protein (ECP) which are toxic to epithelial cells.

Oedema, vascular congestion and infiltration by oesinophils produce the

Charcot Leyden crystals.

iii). Vascular Epithelium - exhibits congestion, leakage, increased permeability

and contraction. 2 agonists and theophylline can prevent the contraction.

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

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 PATHOLOGY

Macroscopy (at autopsy)

Overinflated lungs that do not deflate when the thorax is opened

Widespread plugging of airways with thick mucous

Diagram 7.4: Pathological Changes in Asthma

Microscopy

Desquamation of the epithelium

Hypertrophy of smooth muscle

Thickening of the basement membrane

Infiltration by oesinophils and inflammatory cells

Page 50 Carey Francis Okinda

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.

6.0 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 (pulsus paradoxicus)

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%

7.0 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

TASK

Outline the clinical classification of asthma stating the main

clinical features

Page 51 Carey Francis Okinda

8.0 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

Diagram 7.5: Lung Volumes

Diagram 7.6: 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 (normal -

oxygen PaO2 is over 12 kPa (90 mmHg) and PaCO2 is less than 6.0 kPa

(45 mmHg). This is reversed in asthma due to carbon dioxide retention

resulting from the physiological valve.

Page 52 Carey Francis Okinda

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

9.0 COMPLICATIONS

1. Pneumothorax

2. Pneumomediastinum

3. Respiratory failure

4. Heart failure/CCF/Cor Pulmonale

5. COPD

6. Pneumonia

7. Lung Collapse

What is the pathophysiology of these complications?

Page 53 Carey Francis Okinda

Lesson 8: 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) Investigate patients with restrictive lung diseases

1.0 INTRODUCTION

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

ARLD is characterized by oedema and exudation

CRLD diseases present with inflammation and fibrosis and 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: - kyphosis, poliomyelitis and

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

3.0 PATHOGENESIS

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 8.1: Pathogenesis of Restrictive Lung Disease

Stimuli Inflammation

Increased accumulation of lymphocytes, macrophages, neutrophils, oesinophils

Widespread destruction - “HONEYCOMB” lung

Alveolitis

Inflammatory destruction of pulmonary parenchyma

Fibrosis

Page 54 Carey Francis Okinda

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/Cor pulmonale

8) Reduced CO diffusing capacity

9) Reduced lung volume

10) Reduced lung compliance

5.0 PNEUMOCONIOSIS

Lung disease caused by inhalation of dust (dust diseases/occupational lung

disease)

Type of disease produced varies according to the nature of the dust causing

the problem

Extent of damage caused by inhaled gases is determined by -

1. Size and shape of the particles

2. Solubility and physiochemical composition

3. Amount of dust retained in the lungs

4. Additional effects of other irritants such as

tobacco.

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

Tissue response will include –

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

2. Interstitial fibrosis e.g. asbestosis

3. Hypersensitivity reactions – e.g. in berylliosis

6.0 FIBROSING LUNG DISEASE (INTERSTITIAL LUNG DISEASE)

Fibrosing lung disease is characterized by chronic inflammation in the walls

of the alveoli resulting in progressive diffuse fibrosis in the lung

parenchyma

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

Find out the inorganic

(mineral dusts) and

organic (biologic) dusts

Page 55 Carey Francis Okinda

7.0 SILICOSIS

Caused by prolonged exposure to silicon dioxide (silica/quartz)

Common in slate mining, metal foundries, stone masonry, tunnelling,

granite quarrying and coal mining

Lung lesions slowly progress over many years

Damages lung macrophages and if the exposure is chronic thus leads to

death of macrophages

There is release of cytokines, which enhance fibrosis. A silicotic lung is

susceptible to tuberculosis

Clinical Features

Dyspnoea

Complications

1. Obstructive pulmonary disease

2. pulmonary tuberculosis

3. rheumatoid arthritis (Caplan’s syndrome)

4. Cor pulmonale

8.0 ASBESTOSIS

Causes lung and pleural diseases

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, cor pulmonale and various forms of cancer

9.0 ADULT ACUTE RESPIRATORY DISTRESS SYNDROME

ARDS is a manifestation of diffuse alveolar damage with widespread

systemic metabolic derangements

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

Page 56 Carey Francis Okinda

8) Massive blood transfusion

9) Acute pancreatitis

10) Radiation injury

Pathogenesis

Diagram 8.2: Pathogenesis of ARDS

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) pneumonitis Immune mediated inflammation of the lung

tissues - 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

Progression to fibrosis of alveoli Restrictive lung disease

“Honeycomb” lung with numerous cysts especially in the lower lobes

Right Ventricular Failure

Pulmonary hypertension

Hypoxia Respiratory failure

Right ventricular hypertrophy

Compare and contrast obstructive and restrictive lung diseases

Page 57 Carey Francis Okinda

Lesson 9: Pulmonary Infections – 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) Investigate pneumonia

1.0 INTRODUCTION

Respiratory tract infections are more frequent than any other infections.

Majority 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

Impairment of the defence mechanisms includes -

1. Loss or decreased/suppression of cough reflex leading to aspiration

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

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 jiroveci

2.0 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

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).

3.0 PREDISPOSING FACTORS

Viral infections, hospitalization, cigarette smoking, alcohol excess,

bronchiectasis, bronchial obstruction, immunosuppression, intravenous

drug use, inhalation, crowding, post operation

How would these factors predispose individuals to pulmonary infections?

Page 58 Carey Francis Okinda

4.0 ROUTES OF INFECTION

1. Inhalation of microbes present in the air

2. Aspiration – naso and oropharynx

3. Haematogenous spread from a distant foci of infection

4. Direct spread from an adjacent site of infection

5.0 PATHOGENESIS

A number of defence mechanisms at different levels normally protects the

lung and failure of the defence mechanisms and presence of predisposing

factors results in development of pneumonia.

Such situations include -

a) Altered consciousness - oropharyngeal contents can be aspirated into

the lungs in states of unconsciousness e.g. coma, cranial trauma,

seizures, cerebro-vascular accidents, drug overdose and alcoholism.

b) Depressed cough and gag reflexes - allows aspiration of gastric contents

e.g. in old age, pain from trauma, thoraco-abdominal surgery,

neuromuscular disease, malnutrition, kyphoscoliosis, severe obstructive

pulmonary disease, endotracheal intubation and tracheostomy

c) Impaired mucociliary transport - impairment or destruction of the

mucous-covered ciliated epithelium as in cigarette smoking, respiratory

viral infections, immotile cilia syndrome, inhalation of hot or corrosive

gases and old age.

d) Impaired alveolar macrophage function - cigarette smoking, hypoxia,

starvation, anaemia, pulmonary oedema and viral respiratory infections.

e) Endobronchial obstruction - interferes with effective clearance of the

bronchial tree

f) Leucocyte dysfunctions - congenital and acquired immunodeficiency,

HIV/AIDS and granulocyte abnormalities.

Page 59 Carey Francis Okinda

6.0 INVESTIGATIONS

1) Chest x-ray PA and lateral view

o Chest radiography may reveal a lobar consolidation (common in typical

pneumonia most commonly in the lower lobes; or it could show bilateral

diffuse interstitial infiltrates and cavitations.

o Used to evaluate for complications of pneumonia like empyema, lung

abscess, pneumothorax etc.

o Gives a clue for suspecting the aetiological agent.

Multi lobar involvement (Bacteraemic pneumococcal)

Pleural effusions (Bacteraemic pneumococcal)

Lymphadenopathy (Mycoplasma infection)

Multilobe involvement, cavitation, or spontaneous pneumothorax

(Staphylococus aureus).

Upper lobe preponderance may denote klebsiella pneumonia.

2) Chest CT (computed tomography) can reveal pneumonia that is not seen

on chest x-ray

3) HIV serology

4) Lung Function Tests

5) Blood picture

o Show a high blood cell count, indicating the presence of bacterial

infection.

o Leucopenia may suggest viral pneumonia.

6) Sputum gram stain and culture

o The presence of > 25 white blood cells and, 10 squamous epithelial

cells per high power field suggests that the sputum is appropriate for

examination.

o Specialized cultures for Mycobacterium sp., Legionella sp., and endemic

fungi may be valuable in the appropriate clinical circumstance. If the

patient is not receiving antibiotics at the time of admission

7) Sputum culture and sensitivity results may be useful

8) Blood culture

9) Urea and electrolytes

10) Blood chemistry

a) Glucose

b) Electrolytes

c) Liver and renal function tests

11) Pulse oximetry

12) Arterial Blood Gases – If oxygen saturation < 90%

13) Serum antibodies - Detection of antibodies to Streptococcus pneumonia,

mycoplasma, chlamydia, adenovirus, influenza A and B viruses,

parainfluenza viruses 1, 2, and 3, and respiratory syncytial virus etc.

14) Polymerase Chain Reaction (PCR) - useful for identifying certain atypical

bacteria strains, including mycoplasma, Chlamydia pneumonia and

Haemophilus influenzae type b. One study found that using a real-time PCR

Page 60 Carey Francis Okinda

test may help quickly diagnose Pneumocystis pneumonia in HIV positive

patients.

15) Urine antigen tests for Legionella pneumophila (Legionnaires’ disease)

and Streptococcus pneumonia may be performed in patients with severe

CAP.

16) Thoracentesis if pleural effusion is significant

a) Pleural fluid thickness > 10 mm thickness in lateral decubitus view.

17) Bronchoscopy – Bronchoalveolar lavage, protected specimen brush

18) Biopsy 7.0 CLASSIFICATION

Basis Types

Aetiologic classification Bacterial; Viral; Rickesttsiae; Protozoa;

Mycoplasma; Fungal; Chemical

Pathologic classification–

how the infection spreads

within the lung

Lobar pneumonia and Bronchopneumonia

Clinical classification –

circumstances surrounding

development of disease

Community acquired disease; Hospital acquired

(nosocomial) infections; Post-operative

pneumonia/hypostatic pneumonia; Aspiration

pneumonia; Obstructive pneumonia; Disease

acquired in special environments; Disease in

immunosuppressed patients

BACTERIAL PNEUMONIA

Most common cause of pneumonia or consolidation of one or both lungs

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

May involve a part of the lobe, the entire lobe or even two lobes of one or

both the lungs

More common in males that females and allergy plays an important role in

the aetiology and pathogenesis of lobar pneumonia.

2.0 Aetiology

1) Pneumococcal pneumoniae (Streptococcus pneumoniae) – 90% of lobar

pneumonia and it is mainly a community acquired infection. Beta haemolytic

streptococcus is common in children after measles or influenza infections,

severely debilitated, elderly and diabetic patients

2) Staphylococcus aureus – haematogenous spread and following viral

infection

3) Pneumonia by gram negative aerobic bacteria – this is less common.

Organisms include: - H. influenzae (common in children less than 3 years old

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and after a preceding viral infection), Klebsiella pneumoniae (Frielander’s

bacilli), Pseudomonas aeroginosum, Proteus, Escherichia coli

3.0 Pathogenesis

Microbes gain access to the lungs via several routes because of failure of

the lung defence mechanisms and presence of the relevant predisposing

factors.

Invasion of the lungs results in inflammation of the alveolar with production

of an 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.

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.

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

Lower lobes affected most

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

Diagram 9.1: Lobar Pneumonia

4.1. Congestion (Initial Phase)

Lasts 1 – 2 days; represents the early acute inflammatory response to

bacterial infection

Characterized by extreme congestion and excessive serofibrinous

exudation which results from outpouring of protein-rich exudates into the

alveoli

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Associated with dramatic onset of increased temperature with chills and

rigors

Cough is first dry and in 1-2 days rusty sputum is expectorated

Macroscopy

o Enlarged lobe, heavy, dark red and congested and cut surface – exudate

blood stained frothy fluid

Microscopy

i) Typical features of acute inflammation

ii) Dilatation and congestion of capillaries in alveolar walls

iii) Oedema fluid

iv) Few red blood cells and neutrophils

v) Numerous bacteria

4.2. Red Hepatization

Lasts from 2nd – 4th day

Characterized by liver-like consistency 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

4.3. Grey Hepatisation

Lasts from the 4th – 8th day

Occurs due to accumulation of fibrin in the lung spaces.

Macroscopy

i) Lobe is firm, heavy and more friable lung

ii) Cut surface is dry, granular and grey in appearance with a liver like

consistency

iii) Fibrinous pleurisy is prominent

Microscopy

i) Numerous and dense fibrous strands

ii) Reduced neutrophils exudation due to disintegration of neutrophils

iii) Fewer red blood cells

iv) Macrophages begin to appear

v) Thin clear space separates cellular exudates from the septa walls

vi) Polymorph leucocytes present in large numbers and produce a

proteolytic enzyme

vii) Vessel congestion is reduced in the inter alveolar walls

viii) Exudate in pleural space is partially organized

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4.4. Resolution

Resolution begins on the 8th or 9th day if no chemotherapy is administered

and is completed in 1 – 3 weeks

Antibiotic therapy induces resolution on about the 3rd day

Proceeds in a progressive manner.

Macroscopy

i) The solid fibrinous constituent is liquefied by enzymatic action restoring

normal aeration in the affected lobe

ii) Softening of the lobe begins centrally and spreads to the periphery

iii) Exudates is removed by coughing/expectoration, phagocytosis and

liquefaction

iv) Cut surface is grey-red or dirty brown and frothy and yellow creamy

fluid can be expressed on pressing

v) Resolution of pleural reaction may undergo organization forming a

fibrous obliteration of pleural cavity.

Microscopy

i) Macrophages are predominant and have engulfed neutrophils and

debris

ii) Reduced neutrophils

iii) Granular and fragmented fibrous strands in alveolar spaces

iv) Engorged alveolar capillaries

v) 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

Stage Symptoms Signs

Congestion

Red hepatisation

Grey hepatisation

Resolution

6.0 Investigations

1) Full haemogram – neutrophils leucocytosis, raised ESR

2) Positive blood cultures

3) Sputum examination

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4) Chest X-ray – consolidation

5) Ultrasound

6) CT scan

7.0 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/Lung abscess

4) Emphysema

5) Lung collapse

6) Pneumothorax

7) Thromboembolism

8) Lobar gangrene

9) Metastatic infection(bacteraemia) - pericardium – pericarditis,

myocarditis, endocarditis; otitis media, mastoiditis; meningitis; brain

abscess; purulent arthritis; peritonitis

10) Multiple organ failure

Bronchopneumonia

Is inflammation of the terminal bronchioles that extends into the surrounding

alveoli resulting in patchy consolidation of the lungs

Involves both the right and left lung fields

Particularly frequent at extremes of life (infancy and old age), chronic

debilitating diseases and post operatively

Susceptibility in children is due to poor propulsive power (cough reflex),

delicate mucosa and a short wide bronchiole tree. 1.0 Aetiology

Staphylococcus, Streptococcus, Pneumococci, Klebsiella pneumonia,

Heamophilus influenza, Gram-negative bacilli – Pseudomonas, Coliform

bacteria

2.0 Pathogenesis

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

the bronchioles of both lungs. 3.0 Pathology

Macroscopy

1) Patchy 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

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above the surface and can easily be felt by passing fingertips on the cut

surface.

Diagram 8.2: Bronchopneumonia

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 Infection of a part of a lobe of

one or both lungs or the

entire lobe(s)

Infection of the terminal bronchioles

extending in to the adjoining alveoli

Age group More common in adults Common at extremes of ages

Predisposing

factors

More often affects healthy

persons

Pre-existing disease

Common

aetiologic

agents

Pneumococci, Klebsiella

pneumonias,

Staphylococcus,

Streptococcus

Staphylococcus, Streptococcus,

Pseudomonas, Heamophilus

infleunzae

Pathologic

features Congestion (1-2 days)

Early (red hepatisation) 2

– 4 days

Late consolidation (grey

hepatisation) 4 – 8 days

Resolution (1 – 3 weeks)

Patchy consolidation

Alveolar exudation

Investigations Neutrophil leucocytosis

Positive blood culture

X-ray shows consolidation

Neutrophil leucocytosis

Neutrophil leucocytosis

X-ray shows spotted focal opacities

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Prognosis Good response to

treatment, resolution is

common, good prognosis

Variable

Prognosis poor

Complications Pleural effusion ,

Empyema, Lung abscess,

Organization

Bronchiectasis, Pleural effusion,

Empyema, Lung abscess,

Organization

4.0 Clinical Features

5.0 Investigations

As lobar pneumonia

6.0 Complications

19) as lobar pneumonia

20) Bronchiectasis

Community Acquired Pneumonia (CAP) 1.0 Introduction

CAP is pneumonia that has been acquired in a community in a patient who

has not been hospitalized within 14 days prior to onset of symptoms or

hospitalized less than 4 days prior to onset of symptoms

One of the most common infectious diseases

Important cause of mortality and morbidity worldwide

2.0 Aetiology

Typical CAP pathogens

Streptococcus pneumonia, Haemophilus influenza, Moraxella catarrhalis;

Staphylococcus aureus, K pneumoniae, and Pseudomonas aeruginosa are not

typical causes of CAP in otherwise healthy hosts.

Other gram-negative pathogens (e.g., Enterobacter species, Serratia

species, Stenotrophomonas maltophilia, Burkholderia cepacia) rarely cause

CAP.

Atypical CAP pathogens

1) Zoonotic atypical CAP pathogens include Chlamydophila (Chlamydia)

psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii

(Q fever).

2) Nonzoonotic atypical CAP pathogens include Legionella species, M

pneumoniae, and Chlamydophila (Chlamydia) pneumoniae. These

organisms account for approximately 15% of all CAP cases.

What are the clinical features of bronchopneumonia?

Page 67 Carey Francis Okinda

3.0 Pathophysiology

Six mechanisms describe the pathophysiology

i) Inhalation of infectious particles

ii) Aspiration of oropharyngeal or gastric contents

iii) Haematogenous deposition

iv) Invasion from infection in contiguous structures

v) Direct inoculation

vi) Reactivation

4.0 Differential Diagnosis

1) Acute bronchitis

2) Myocardial infarction

3) Congestive heart failure and pulmonary oedema

4) Pulmonary fibrosis

5) Sarcoidosis

6) SLE pneumonitis

7) Pulmonary drug hypersensitivity reactions (nitrofurantoin)

8) Drug-induced pulmonary disease

9) Pulmonary embolus or infarction

10) Bronchogenic carcinomas

11) Radiation pneumonitis

12) Lymphomas

13) Tracheobronchitis

5.0 Grading

5.1. CURB-65

CURB score and its modification (CURB-65).

Criteria Score

C Confusion of new onset (mini mental

score<8)

1

U Urea >7 mmol/L 1

R Respiratory rate >30/min 1

Bp <90 mmHg systolic and/or <60 mmHg

diastolic

1

65 yrs Age >65 1

Interpretation

65

years

Risk

group

Mortality Management

0 – 1 1 1.5% Home

2 2 9.2% Admission

3 - 5 3 22% Severe

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5.2. Pneumonia Severity Index (PSI)

1) Criteria

a) General

i) Age in years + 1 point per year

ii) Gender - 10 points for women

iii) Nursing Home resident + 10 points

b) Past medical history

i) Cancer + 30 points

ii) Liver Disease + 20 points

iii) CHF + 10 points

iv) CVA + 10 points

v) Chronic Kidney Disease + 10 points

c) Examination findings

i) Altered Level of Consciousness + 20 points

ii) Breathing Rate >30 rpm + 20 points

iii) Systolic BP <90 mmHg + 20 points

iv) Temperature not 35-40 C + 15 points

v) Heart Rate >125 bpm + 10 points

d) Labs: Arterial Blood Gas (ABG)

i) Arterial pH <7.35 + 30 points

ii) PaO2 <60 mmHg (<90% O2 Sat) + 10 points

e) Labs: Serum Chemistry

i) Serum Sodium <130 mEq/L + 20 points

ii) BUN >64 mg/dl + 20 points

iii) Serum Glucose >250 mg/dl + 10 points

f) Labs: Blood Count

i) Hematocrit <30% + 10 points

g) Chest X-ray

i) Pleural Effusion: + 10 points

2) Scoring

Class Points Mortality

1 0 0.1% (low risk)

2 < 70 0.6% (low risk)

3 71-90 2.8% (low risk)

4 91-130 8.2% (moderate risk)

5 >130 29.2% (high risk)

3) Interpretation

a) Class 1-2: Outpatient management

b) Class 3: Consider short observation hospital stay

c) Class 4-5: Inpatient management

PSI

Minor criteria:

1. Respiratory rate ≥30 breaths/min

2. PaO2/FiO2 ratio ≤ 250

3. Multilobar infiltrates

4. Confusion/disorientation

5. Uraemia (BUN level ≥20mg/dL)

6. Leukopenia (WBC <4000 cells/mm3)

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7. Thrombocytopenia (platelet count <100,000 cells/mm3

8. Hypothermia (core temperature <36oC)

9. Hypotension requiring aggressive fluid Resuscitation

Major criteria

1. Invasive mechanical ventilation

2. Septic shock with the need for vasopressors.

Diagnosis

Admission to ICU is warranted if 1 major or 3 minor criteria are fulfilled

Aspiration Pneumonia 1.0 Introduction

Is a pulmonary squeal resulting from the abnormal entry of endogenous

secretions or exogenous substances into the lower airways

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 - alcoholism; seizures; cerebrovascular accidents;

head trauma; general anaesthesia and 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

Three distinctive syndromes based on inoculation, pathogenesis of

pulmonary complications, clinical presentation and treatment.

These include

i) Chemical pneumonitis

ii) Bacterial infection

iii) Mechanical obstruction

What are the relevant investigations in community acquired pneumonia?

What are the likely findings of such investigations?

Page 70 Carey Francis Okinda

3.1. Chemical Pneumonitis

Fluids inherently toxic to the lower airways and can initiate an inflammatory

reaction that is independent of bacterial infection

Examples of such fluids include – acids (e.g. gastric acid – most common),

volatile hydrocarbons (gasoline, kerosene and animal fats/milk), mineral oil

and alcohol.

Pathogenesis and Pathology

Acids induce an inflammatory reaction (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

i) Atelectasis

ii) Peribronchial haemorrhage

iii) Pulmonary oedema

iv) Degeneration of the bronchial epithelium

Microscopy

i) Early necrosis of type I alveolar cells

ii) Fibrin

iii) Polymorph nuclear infiltration

iv) Alveolar type II cells degenerate as type I cells necrose further and

detach from the basement membrane

v) 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 - reduced lung compliance; abnormal ventilation-perfusion

ration; reduced diffusing capacity; reduced PO2; respiratory alkalosis;

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.

Page 71 Carey Francis Okinda

Patients with severe aspiration pneumonia progress into adult respiratory

distress syndrome (ARDS).

3.2. Bacterial Infection

Most common form of aspiration pneumonia

Bacteria such as Streptococcus pneumoniae, Heamophilus influenzae, gram-

negative bacilli and Staphylococcus aureus are relatively virulent in lower

airways and a small inoculation is all that is required for the infection to take

root

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

Aspirated inoculum is generally composed of oropharyngeal secretions

harbouring bacteria from various sources in the upper airway

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

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.

3.3. Mechanical Obstruction

Is squeal 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

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

Particles involve the usual objects such as peanuts, vegetable particles,

inorganic material, and teeth just to mention a few

Page 72 Carey Francis Okinda

Vegetable materials are bad because they swell due to their hydroscopic

properties and the undigested cellulose cats as a local irritant causing

inflammation.

Hypostatic Pneumonia

Occurs as a result of collection of oedema fluid and secretions in

dependent zones of the lungs

Fluid then gets infected by bacteria from the upper respiratory tract

Common in severely debilitated, bed-ridden patients, old, feeble, and

comatose patients.

Nosocomial (Hospital-Acquired) Pneumonia

Acquired in the course of stay in the hospital. They are life-threatening

infections

Is a new episode of pneumonia occurring at least 2 days after admission to

hospital

Encompasses post-operative and certain forms of aspiration pneumonia.

Common in patients with severe underlying disease, immunosuppression,

prolonged antibiotic therapy or invasive devices and procedures e.g.

intravenous catheters.

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

2. Aspiration of nasopharyngeal or gastric secretions

3. Bacteria introduced into the lower respiratory tract

4. Bacteraemia

Investigations

1) Arterial blood gas analysis

2) Blood cultures

3) Chest x-ray

4) CT scan

5) Complete blood counts (CBC)

6) Pulse oximetry

7) Sputum culture

Which microbes will stand accused in hypostatic pneumonia?

What are the complications of aspiration pneumonia?

Page 73 Carey Francis Okinda

Atypical Pneumonia

Viral Pneumonia & Pneumonia in the Immunocompromised

Individuals

Differential Diagnosis of Pneumonia

1. Pulmonary infarction

2. Pulmonary/pleural tuberculosis

3. Pulmonary oedema

4. Inflammatory conditions below the diaphragm

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?

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?

Page 74 Carey Francis Okinda

Lesson 10: Pulmonary Infections – Lung Abscess

Learning Outcomes

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

1) Identify the causes of lung abscess

2) Discuss predisposing factors

3) Describe the pathology of lung abscess

4) Discuss the investigations in lung abscess

1.0 INTRODUCTION

Is a collection of pus within a destroyed portion of the lung following a

pulmonary infection with parenchymal necrosis

Is a localized area of necrosis of lung tissue with suppuration that is usually

solitary but occasionally multiple in necrotizing pneumonia

Overlap of aspiration pneumonia, lung abscess and necrotizing pneumonia

results in empyema (collection of pus within the pleural cavity).

Necrosis of the pulmonary tissue & formation of cavities containing necrotic

debris or fluid caused by microbial infection

Formation of multiple small (< 2 cm) abscesses is occasionally referred to

as necrotizing pneumonia or lung gangrene

Diagram 10.1: Lung Abscess

2.0 CLASSIFICATION

Classified based on the duration & the likely aetiology.

Duration

Acute abscesses are less than 4-6 weeks old and chronic abscesses are of

longer duration.

Page 75 Carey Francis Okinda

Aetiology

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.

Primary abscess is infectious in origin, caused by aspiration or pneumonia

in the healthy host.

Secondary lung abscess

Develop as a complication of other lung diseases or from another site.

Caused by pre-existing condition (obstruction), spread from an extra-

pulmonary site, bronchiectasis, and an immuno-compromised state.

Mostly small and multiple post-pneumonic or septic emboli.

3.0 PREDISPOSING FACTORS

1. Pulmonary infections e.g. bronchitis, broncho and lobar pneumonia

2. Cachexia/emaciation/Malnutrition

3. Otitis media

4. Chronic alcoholism

5. Chronic nephritis

6. Smoking

7. Malignancy

4.0 AETIOLOGY

Mainly caused by bacteria

About 65% of infections are produced by anaerobes

Causes

1) Bacteria – Streptococcus pyogenes (Group A -haemolytic),

Streptococcus pneumonia, Staphylococcus aureus, Anaerobic bacteria,

Entero Gram negative bacteria – Klebsiella, Mycobacterium –

Mycobacterium tuberculosis, Pseudomonas aeruginossa, Pseudomonas

pseudomallaei, Legionella, H. Influenza, Nocardia

2) Actinomycosis

3) Fungi –Cryptococcus neoferan, Aspergillus, Histoplasma capsulatum

4) Parasites – Entamoeba histolytica

5.0 MECHANISM OF INFECTION (PATHOGENESIS)

A. Preceding Bacterial Infections (inoculation)

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

Page 76 Carey Francis Okinda

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, 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.

Page 77 Carey Francis Okinda

C. Bronchial obstruction - Obstruction results in development of an abscess

distal to the site of obstruction

Diagram 9.3: Sites of Abscess in Bronchial Obstruction

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.

Commonly occurs in patients with a predisposition to gastric content

aspiration due to altered consciousness

Aspiration of gastric contents can also result from dysphagia associated with

neurological or oesophageal disease

Common causes of gastric content aspiration include alcoholic stupor,

seizures, stroke, neurological bulbar dysfunction, drug overdose, and

general anaesthesia. Other causes include dental or oropharyngeal surgery

(especially tonsillectomy in the sitting position) and oesophageal diseases

(stricture, malignancy, and reflux)

Nasogastric and endotracheal tubes that interfere with normal anatomical

barriers predispose to aspiration of oropharyngeal fluid. Aspiration of

contaminated oropharyngeal secretions results in necrotising infection that

follows a segmental distribution limited by the pleura.

Bacterial inoculums from the gingival crevice reaches the lower airways &

infection is initiated coz the bacteria are not cleared by the patient’s host

defense mechanism.

Page 78 Carey Francis Okinda

Abscesses generally develop in the right lung and involve the posterior

segment of the right upper lobe, the superior segment of the lower lobe, or

both. This is due to gravitation of the infectious material from the oropharynx

into these dependent areas.

Initially, the aspirated material settles in the distal bronchial system and

develops into a localized pneumonitis. Within 24-48 hours, a large area of

inflammation results, consisting of exudate, blood, and necrotic lung tissue.

The abscess frequently connects with a bronchus and partially empties

Other mechanisms for lung abscess formation include :

Septic emboli to the lung ,caused by:

1) Bacteraemia.

2) Tricuspid valve endocarditis.

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

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

Page 79 Carey Francis Okinda

10.0 DEFERENTIAL DIAGNOSIS

1) Alcoholism

2) Pleuro-pulmonary empyema.

3) Hydatid Cysts.

4) Lung Cancer.

5) Mycobacterium.

6) Pneumococcal infections.

7) Pneumocystis Carnii pneumonia.

8) Aspiration pneumonia.

9) Bacterial pneumonia.

10) Fungal pneumonia.

11) Pulmonary embolism.

12) Sarcoidosis.

13) T.B

11.0 SQUEAL 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

12.0 INVESTIGATIONS

COMPLICATIONS

1. Pleural effusion

2. Empyema

3. Haemorrhage

4. Septic embolization

5. Secondary amyloidosis

6. Haemoptysis

7. Bronchopleural fistula

8. Brain abscess

What is the pathophysiology of these complications?

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

pneumonia

Page 80 Carey Francis Okinda

Lesson 11: Pulmonary Tuberculosis (PTB)

Learning Outcomes

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

1) Discuss the pathology of pulmonary tuberculosis

2) Describe the clinical presentation of pulmonary tuberculosis

3) Investigate pulmonary tuberculosis

1.0 INTRODUCTION

Tuberculosis (TB) is a multisystemic disease with myriad presentations and

manifestations

Caused mainly Mycobacterium 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

TB is made distinctive by a necrotizing (caseating) granulomatous tissue

response to seeded organisms (it exhibits a granulomatous inflammation).

2.0 CAUSATIVE AGENT

Mycobacterium tuberculosis a strict aerobe bacillus/rod that thrives best

in high oxygen tension areas like the apex of the lung

Are acid-fast, slender rod, aerobic, non-motile, non-capsulated and non-

sporing organisms.

mycobacterium tuberculosis is rapidly killed by exposure to direct sunlight

If it is protected from sunlight, it remains alive and infectious for up to ten

weeks (for example in dried saliva)

Can withstand most disinfectants and often remains in its dormant state

Reproduces itself every 24 to 48 hours.

Mycolic acid sits on the cell wall and protects the bacillus against the body’s

immune response. The mycolic acids are responsible for a particular

characteristic of all mycobacteria, which is used to identify Mycobacterium

tuberculosis in diagnostic tests.

3.0 TRANSMISSION

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

Can only occur from people with active (not latent) TB and the probability

of transmission from one person to another depends upon the number of

infectious droplets expelled by a carrier, the effectiveness of ventilation, the

duration of exposure, and the virulence of the M. tuberculosis strain.

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

Page 81 Carey Francis Okinda

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;

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)

Table 11.1: Factors that Determine Probability of Transmission

Factor Description Examples

Susceptibility Immune status

of the exposed

individual

Infe

cti

ou

sne

ss

Directly

related to the

number of

tubercle bacilli

that he or she

expels into the

air.

Persons who

expel many

tubercle bacilli

are more

infectious than

patients who

expel few or no

bacilli

Clinical [presence of cough ≥ 3 weeks,

respiratory tract disease, especially with

involvement of the larynx (highly

infectious), failure to cover the mouth and

nose when coughing,

Inappropriate/inadequate treatment]

Procedure[undergoing cough-inducing or

aerosol-generating procedures (e.g.,

bronchoscopy, sputum induction,

administration of aerosolized medications],

Radiographic and laboratory [cavitation on

chest radiograph, positive culture for M.

tuberculosis, positive AFB sputum smear

result]

En

vir

on

me

nt

Environmental

factors that

affect the

concentration

of M.

tuberculosis

organisms

Concentration - the more droplet nuclei in

the air, the more probable that M.

tuberculosis will be transmitted

Exposure in small, enclosed spaces

Inadequate local or general ventilation that

results in insufficient dilution or removal of

infectious droplet nuclei

Air ventilation - recirculation of air

containing infectious droplet nuclei

Improper specimen handling procedures

that generate infectious droplet nuclei

Air pressure - positive air pressure in

infectious patient’s room that causes M.

tuberculosis organisms to flow to other

areas

Ex

po

sure

Proximity,

frequency, and

duration of

exposure

Exposure - the longer the duration, the

higher the risk for transmission

Frequency - the more frequent the

exposure, the higher the risk

Proximity - the closer the proximity, the

higher the risk

Page 82 Carey Francis Okinda

4.0 PREDISPOSING/RISK FACTORS

Strong Factors

1. Debilitating or immunosuppressive conditions e.g. Diabetes mellitus,

Chronic lung disease, End stage renal disease, HIV/AIDS, Alcoholism,

Hodgkin’s disease

2. Exposure to infection

3. Malignancy

Weak Factors

Smoking; Inadequate medical care; Poverty; Crowding; Malnutrition;

Occupation; Cultural practices; Age (<5 and > 65 years; Alcoholism; End stage

renal disease (ESRD); IV drug use; High risk concrete setting – slums,

overcrowding, homeless, prisons

5.0 SITES

1) Pulmonary (Lungs) - 85%

2) Extra pulmonary - Mediastinal, retroperitoneal and cervical lymph nodes;

vertebral bodies, adrenals tract

The infected end organs typically have high regional oxygen tension

(kidneys, bones, meninges, eye and choroids, lung apices)

The principal cause of tissue destruction is the organisms’ ability to incite

the intense host immune reaction to antigenic cell wall proteins.

6.0 PATHOGENESIS AND PATHOPHYSIOLOGY

Infection occurs when a person inhales droplet nuclei containing tubercle

bacilli that reach the alveoli of the lungs (droplets are about 1 to 5 microns

in diameter — less than 1/5000 of an inch; can remain suspended in the air

for several hours, depending on the environment

The tubercle bacilli are ingested by alveolar macrophages; the majority of

these bacilli are destroyed or inhibited

Droplet nuclei containing tubercle

bacilli are inhaled, enter the lungs,

and travel to the alveoli

TB infection begins when the mycobacteria reach the pulmonary alveoli,

where they invade and replicate within the endosomes of alveolar

macrophages

Page 83 Carey Francis Okinda

Tubercle bacilli multiply in the

alveoli

TB disease develops when the immune system cannot keep the tubercle

bacilli under control and the bacilli begin to multiply rapidly.

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 forming a Ghon complex

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.

A small number of tubercle bacilli

enter the bloodstream and spread

throughout the body. The tubercle

bacilli may reach any part of the

body, including areas where TB

disease is more likely to develop

(such as the brain, larynx, lymph

node, lung, spine, bone, or kidney).

Within 2-10 weeks, the immune system produces special immune cells

called macrophages that surround the tubercle bacilli. The cells form a hard shell that keeps the bacilli contained and under control (TB

infection)

If the immune system cannot keep the bacilli under control, the bacilli begin to multiply rapidly (TB disease). This process can occur in

different places in the body, such as the lungs, kidneys, brain, or bone

Page 84 Carey Francis Okinda

7.0 IMMUNOLOGY

May be either natural or acquired

Acquired immunity is intimately associated with development of allergy

(hypersensitivity). Hypersensitivity (allergy) and immunity play as

significant role in development of lesion in tuberculosis.

The tubercle bacilli do not produce anti toxins and tissue changes seen in

tuberculosis are because of host response to the organism, which leads to

development of cell-mediated hypersensitivity (type IV) and immunity.

These responses are due to the presence of several lipids such as mycosides

and glycoproteins.

Immune 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.

Effectiveness of immune mechanisms that are responsible for bacillary

destruction are influenced by: -

1) Environmental factors

2) Hereditary factors and race

3) Developmental factors – infancy, puberty and senility

4) Nutrition

5) Stress

6) Cellular immunodeficiency

7) Diabetes

8) Sarcoidosis

Acquired Immunity and Hypersensitivity

Acquired Immunity

Mediated through cellular and biochemical mechanisms linked with

delayed hypersensitivity

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 response, 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)

Page 85 Carey Francis Okinda

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

Induced by vaccination using a live attenuated mycobacterium organism

(BCG)

Natural Immunity - Rare/varies with race

8.0 PATHOLOGY - LESIONS IN PTB

The basic types of tissue change in tuberculosis include -

1) Exudative lesion

2) Proliferative lesions

3) Caseation and cavity formation

4) Tubercle or granuloma formation

1. Exudative Lesions

Predominate when large numbers of bacilli are present and host defences

are weak

Comprise of large aggregates of immature macrophages, neutrophils,

fibrin and caseation necrosis

Without treatment lesion progress and infection spreads

Forms three patterns namely fibrinomacrophagic, polymorphonuclear and

fibrinous alveolitis

2. Proliferative Lesions

Develop when bacillary load is small and host cellular immune responses

Tubercles are compact with activated macrophages admixed and

surrounded by proliferating lymphocytes, plasma cells

Bacillary load remains low

3. Caseation and Cavity Formation

Necrosis produces the caeous (cheesy) material may undergo two

processes

i) 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)

ii) 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. Softening is accompanied by intense multiplication of

tubercle bacilli.

Page 86 Carey Francis Okinda

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 forming a cavity

Tissues within areas of caseation necrosis have high levels of fatty acids, low

pH and low oxygen tension all of which inhibit growth of the tubercle bacilli

Diagram 11.1: Cavity

4. Tubercle or Granuloma Formation

May proceed or follow necrosis

Polymorphonuclear and mononuclear macrophages appear and continue to

phagocytose tubercle bacilli at the periphery of the lesion (granulomatous

inflammation)

Macrophages undergo structural changes (increase in size, cytoplasm

becomes pale and oesinophilic and their nuclei become elongated and

vesicular) making them resemble epithelial cells (are then called epitheloid cells).

Macrophages continue entering the tissues from circulating monocytes or

local proliferation, undergo changes to form more epitheloid cells, and with time adjacent epitheloid cells aggregate into tight clusters or granulomas.

Fate of the granuloma

i) 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.

ii) Sinus formation

iii) Coalesce of adjacent granulomas and progressive fibrosis

iv) Dystrophic calcification

9.0 PATTERNS OF PROGRESSION AND DISSEMINATION

Patterns of progression and dissemination of tuberculosis are -

1. Direct extension

Depends on population of bacilli, vascularity of tissues involved and

susceptibility of the host

Page 87 Carey Francis Okinda

2. Ductal or intra-canalicular dissemination

Ductal or intra-canalicular dissemination is very important in pulmonary

tuberculosis.

Sloughed tubercle bacilli are present in the sputum and are carried to

the mucous membranes e.g. the larynx, mouth, pharynx, nose and

middle ear. The organisms may be swallowed into the gastrointestinal

tract resulting in intestinal tuberculosis or peritoneal abscess and fistula.

3. Lymphogenous dissemination

The great number of lymphatic channels in the lungs provides many

opportunities for dissemination of tubercle bacilli. This type of

dissemination is more common and extensive in children.

4. Haematogenous dissemination

Tubercle bacilli may be carried into the blood stream in various ways

such as rupture of liquefied caseous material into a pulmonary vein,

mediastinal lymph nodes in primary tuberculosis and 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 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

Tuberculous Pneumonia

Is an overwhelming infection characterized by extensive tuberculous

consolidation of one or more lobes of the lungs

The TB 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.

Page 88 Carey Francis Okinda

11.0 DISEASE PROGRESSION – STAGES

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.

11.1. Primary TB Infection

Occurs usually in children lacking previous exposure to tubercle bacilli or

vaccinated against 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

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 immunosuppressed

hosts as in HIV/AIDS patients

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

components: - pulmonary component (Ghon focus), lymphatic vessel

component and lymph node component (Hilar)

Pulmonary Component (Ghon’s Focus)

Lesion in the lungs that is a 1 -2 cm diameter solitary area of tuberculous

pneumonia located under the pleura in the lower part of the upper lobe

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

May develop beaded, military tubercles along the path of hilar lymph node.

Lymph node component

Consists of enlarged hilar and tracheo-bronchial lymph nodes in the area

drained

Affected lymph nodes are matted and show caseation necrosis

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

Page 89 Carey Francis Okinda

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

5. Pleural effusion – inflammatory reaction in the adjacent lung induces

development of an effusion in the pleural cavity

6. Tuberculous empyema – infection may involve the pleura directly from the

Ghon’s focus and lead to development of the tubercuolus empyema.

7. Reactivation of primary tuberculosis – lowered immunity and increased

hypersensitivity of the host may result in activation of healed lesions

resulting in progressive secondary tuberculosis. This situation is common in

children.

8. Mechanical effects – large granulomas can obstruct the bronchi leading to

hypoxia and lung collapse (atelectasis)

Diagram 11.2: Chest Radiograph in PTB

11.2. Secondary TB Infection

Denotes active infection in a previously sensitized individual (also called

secondary or post primary or re-infection or chronic tuberculosis)

Most cases represent reactivation of dormant bacilli from primary lesions

Occurs later in life as a reactivation or reinfection

Page 90 Carey Francis Okinda

Generally found in the apices of the lungs because of preference of M.

tuberculosis for high oxygen tensions.

Other sites and tissues include tonsils, pharynx, larynx, small intestine and

the skin.

Secondary tuberculosis lesions may progress to cavity fibrocaseous

tuberculosis, tuberculous bronchopneumonia or miliary tuberculosis

The infection may be acquired from endogenous or exogenous sources. The

endogenous sources include reactivation of the dormant primary complex

while the exogenous is fresh dose of re-infection by the tubercle bacilli.

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

Diagram 11.3: Primary and secondary TB

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)

Cavity developed forms a favourable environment for proliferation of

tubercle bacilli because of the high oxygen tension

Page 91 Carey Francis Okinda

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.

11.3. 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

13.0 INVESTIGATIONS AND DIAGNOSIS

1. History and physical examination

2. Imaging (Chest X-ray)

3. Sputum examination (parameters?)

4. Total blood counts

5. Fibre optic bronchoscopy

6. Biopsies

7. Tuberculin testing

8. PCR test

9. TB antibody testing

10. Nucleic Acid Amplification Test (NAAT)

11. MRI

12. Serological assays

14.0 COMPLICATIONS

1. Pleurisy

2. Ca bronchus

3. Tuberculous Empyema

4. Dissemination to other organs

5. Tuberculosis laryngitis

6. Cor Pulmonale

7. COAD

8. Amyloidosis

9. Aspergilomas

10. Pulmonaty tuberculoma

11. ARDS

1. Explain the pathophysiology of these

complications.

2. What is miliary tuberculosis?

3. What are the features of miliary TB

4. Explain how tuberculosis affects other

organs in the body (extra-pulmonary tuberculosis).

What are the important

parameters?

What are the differentials of TB?

What are the clinical features of PTB?

Page 92 Carey Francis Okinda

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 and pulmonary hypertension

3) Discuss the pathology of pulmonary embolism and infarction

4) 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

PULMONARY OEDEMA

1.0 INTRODUCTION

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

Main cause is LVF, 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)

a. Increased hydrostatic pressure (increased pulmonary venous pressure)

Left heart (ventricular) failure – commonest; Volume overload;

Pulmonary vein obstruction

b. Reduced oncotic pressure – less common

Page 93 Carey Francis Okinda

Hypoalbuminaemia, Nephrotic syndrome, Liver disease, Protein

losing enteropathy

c. Lymphatic obstruction – rare

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

a. Infections e.g. pneumonia and septicaemia

b. Inhaled gases - oxygen and smoke

c. Liquid aspiration - gastric contents and 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

Microscopy

Engorged alveolar capillaries

Alveolar micro haemorrhages

Haemosiderin-laden macrophages (heart failure cells)

Fibrosis and thickening of alveolar walls

5.0 CLINICAL FEATURES

6.0 INVESTIGATIONS

What are the clinical features?

What investigations will be relevant?

What parameters will be significant in these investigations?

Page 94 Carey Francis Okinda

7.0 COMPLICATIONS

PULMONARY HYPERTENSION 1.0 INTRODUCTION

Is a systolic blood pressure in the pulmonary arterial circulation of > 30

mmHg

Normal pressure in the pulmonary system is 30/15 mmHg and 3 – 8 mmHg

in the arteries and veins respectively.

Most important causes of pulmonary hypertension are COAD, fibrosis of the

lungs and chronic pulmonary venous congestion

Pulmonary hypertension causes structural damage to the pulmonary vessels

resulting in increased work on the right side of heart and right ventricular

failure (Cor pulmonale)

2.0 CLASSIFICATION

Can be classified as primary and secondary

3.0 PRIMARY (IDIOPATHIC)

Introduction

Uncommon and the causes are unknown.

Causes

Suggested causes include – neurohormonal vasoconstrictor mechanism,

unrecognized thrombo-embolism or amniotic fluid emboli during pregnancy,

collagen vascular disease, veno-oclusive disease and familial occurrence.

Pathogenesis - Unknown

4.0 SECONDARY

Occurs secondary to a lesion recognized in the heart of lungs

More common.

1) Passive pulmonary hypertension

Commonest

Produced by lesions that increase pressure in the pulmonary veins

(pulmonary venous congestion) e.g. mitral valve disease (mitral stenosis)

and chronic left ventricular failure – severe systemic hypertension, aortic

stenosis and myocardial fibrosis

2) Increased pulmonary blood flow (hyperkinetic or reactive pulmonary

hypertension) e.g. cardiac shunts – PDA, ASD and VSD

3) Vaso-occlusive /Mechanical arterial obstruction

Outline the complications stating their pathophysiology and differentiating

factors

Page 95 Carey Francis Okinda

a. Obstruction – block in pulmonary circulation e.g. multiple

emboli/thrombosis, SCD, schistosomiasis and foreign body emboli (e.g.

in drug addicts)

b. Obliteration – reduced pulmonary vascular bed by chronic parenchymal

lung disease (destruction of lung capillary bed) e.g. chronic

emphysema, chronic bronchitis, bronchiectasis, pulmonary

tuberculosis, pneumoconiosis and interstitial fibrosis

c. Vasoconstrictive - widespread sustained hypoxia results in

vasoconstriction and alveolar hyperventilation and pulmonary

hypertension e.g. high altitude, pathologic obesity (Pickwickian

syndrome), severe hyphoscoliosis; upper airway disease causing

tonsilar hypertrophy

4) Idiopathic

5.0 PATHOLOGY

Heart

Right ventricular hypertrophy and right atrial dilatation

Arteries and small pulmonary arteries

Medial hypertrophy and thickening and reduplication of elastin

Medium sized arteries

Medial hypertrophy

Intimal thickening

Thickening of elastic

Adventitial fibrosis

Large arteries

Atheromatous deposits

6.0 CLINICAL FEATURES

7.0 INVESTIGATIONS

8.0 COMPLICATIONS

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

What investigations will be relevant? What parameters will be significant in these

investigations?

Outline the complications stating their pathophysiology

and differentiating factors

What are the clinical features?

Page 96 Carey Francis Okinda

hypoxaemia resulting in multiple organ failure. It occurs as a complication of

numerous diverse conditions due to injury to the lung and systemic disorders.

2.0 CAUSES

1) Infections

a. Sepsis and diffuse pulmonary infections - viral pneumonia, military

tuberculosis, mycoplasma

b. Gastric aspiration

2) Physical injury

Mechanical trauma – head injury

Pulmonary contusions, near drowning

Fractures with fat embolism, burns, 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 and uraemia

7) Cardiopulmonary by-pass

8) Hypersensitivity reactions

9) Organic solvents

3.0 PATHOGENESIS

Results from widespread acute injury to the alveolar capillary membrane

producing high permeability oedema and inhibiting surfactant function

(especially fibrin monomers)

Diagram 11.1: Pathogenesis of ARDS

Acute Alveolar Damage

Stiff Lung

RESOLUTION DEATH

By activated macrophages (IL-1, IL-

8 and TNF)

ORGANIZATION

By activated neutrophils (proteases, PAF,

oxidants, leukotriences)

Hyaline membrane

Local tissue damage, Intra-alveolar oedema, Surfactant inactivation

Release of cytokines

Page 97 Carey Francis Okinda

Epithelial injury also impairs new surfactant synthesis and inflammation may

exacerbate the injury because of release of oxidants and lysosomal

enzymes from activated leukocytes

Lung compliance (is decreased because many airspaces contain oedema

(and hence cannot accept air) and because abnormally high surface tension

counteracts the negative intrapleural pressure.

4.0 PATHOLOGY

Injury results in increased vascular permeability (involving mainly type I

alveolar) and necrosis that affects both capillary endothelium and alveolar

epithelium resulting in intra-alveolar oedema, congestion, fibrin deposition and eventually HYALINE MEMBRANE.

Macroscopy

1) Stiff, congested and heavy lungs

Microscopy

1) Interstitial and intra-alveolar oedema

2) Necrosis of alveolar epithelium

3) Congestion and intra-alveolar haemorrhage

4) Fibrosis

5) Changes as those seen in bronchopneumonia

5.0 CLINICAL FEATURES

Profound dyspnoea, tachypnoea, cyanosis, hypoxaemia, respiratory

distress

6.0 INVESTIGATIONS

1) Chest X-ray - diffuse bilateral infiltrates

2) Lung volumes

3) Blood counts

7.0 COMPLICATIONS

PULMONARY EMBOLISM AND INFARCTION

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)

Outline the complications stating their pathophysiology and

differentiating factors

Page 98 Carey Francis Okinda

1.0 PREDISPOSING FACTORS

1) Immobility and bed rest

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

2.0 CAUSES

3.0 TYPES OF EMBOLI

1) Thromboembolism

2) Air

3) Bone marrow

4) Fat

5) Amniotic fluid

6) Foreign body

4.0 PATHOPHYSIOLOGY

Pathophysiologic response and clinical significance depends on extent of

obstruction, number of emboli, and status of the cardiovascular system and

release of vasoactive amines.

5.0 CLINICAL FEATURES

Chest pain, dyspnoea, tachypnoea, fever, cough, haemoptysis, pleural

rub, severe – sudden death

1) What are the causes?

2) What is the pathogenesis of pulmonary embolism?

Page 99 Carey Francis Okinda

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 – atmospheric pollutants – petrochemical industries

4) Genetic/familial

5) Precursor lesions – squamous dysplasia and CIS, atypical adenomatous

hyperplasia and diffuse idiopathic pulmonary hyperplasia

6) Dietary factors – increased incidence in vitamin A deficiency

7) Chronic scarring – due to chronic inflammatory changes ,old tuberculosis,

asbestosis, chronic interstitial fibrosis and old infarcts

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 - Fibroma and Fibrosarcoma, Lipoma, Haemangioma

and Lymphangioma

3) Pleural Tumours - Benign mesothelioma and malignant mesothelioma

4) Miscellaneous - Pulmonary blastoma, Malignant melanoma, Malignant

lymphoma

B. SECONDARY TUMOURS

1) Kidney

2) Breast

Page 100 Carey Francis Okinda

3) Testis

4) G.I.T/bowel

5) Thyroid

6) Pancreas

C. TUMOUR LIKE-LESIONS

1) Harmatomas

2) Eosinophilic granuloma

3) Inflammatory pseudo tumours

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

Microscopy

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

What microscopic picture do you expect?

Page 101 Carey Francis Okinda

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), Exophthalmos (sunken eye), Miosis (small pupil)

and anhydrosis (loss of sweating)

Diagram 13.2: Spread of Tumour

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 - fever, weight loss, anaemia and jaundice

2) Local symptoms

Cough, Chest pain, Dyspnoea

Haemoptysis

i) Inflammatory - bronchiectasis, bronchitis, tuberculosis, lung

abscess and pneumoconiosis

ii) Neoplastic - primary and metastatic lung cancer and bronchial

adenoma

iii) Others - pulmonary thromboembolism, LVF, mitral stenosis,

primary pulmonary hypertension, foreign body, trauma and

haemorrhagic diathesis

Page 102 Carey Francis Okinda

3) Bronchial obstruction symptoms e.g. bronchopneumonia, lung abscess,

bronchiectasis, pleural effusion and productive cough

4) Symptoms due to metastasis e.g. Superior vena cava syndrome; Painful

bony lesions; Pathological fractures; Paralysis of recurrent laryngeal

nerve; Neurologic manifestations; Hepatomegally

5) Paraneoplastic– ectopic hormone production

a. ACTH adrenal hyperplasia increased blood cortisol Cushing

syndrome

b. ADH water retention dilutional hyponatraemia

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, 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

Page 103 Carey Francis Okinda

Most associated with ectopic hormone secretions

Cell nuclei resemble an oat 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

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

What are the complications of tumours of the lungs?

What are the important

parameters in the

investigations?

Page 104 Carey Francis Okinda

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

Page 105 Carey Francis Okinda

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, pneumothorax and 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 with 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.

Diseases of the pleura include - inflammations (pleurisy), pleural effusion,

empyema, pneumothorax, haemothorax and 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 NOTE: There could be accumulation of air [pneumothorax [)

PLEURAL EFFUSION

1.0 INTRODUCTION

Is accumulation of fluid in the pleural space

A common manifestation of primary and secondary pleural disease and

complication of malignant disease (breast, lung, lymphoma and other

malignancies.

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 capillary

Page 106 Carey Francis Okinda

permeability, hydrostatic pressure, colloid osmotic pressure and 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.

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.

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 drainage – as in mediastinalcarcinomatosis

Diagram 14.1: Pleural Effusion

Page 107 Carey Francis Okinda

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

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); Tuberculosis

b. Fungal infections

c. Viral infections

d. 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 - Eosophageal perforation, Pancreatic disease, Intra-

abdominal abscess, Diaphragmatic hernia, After liver transplant and

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

Inflammation of the pleura results in pleutitis or pleurisy whose effects depend on the characters of the exudates which can be serous, fibrinous,

serofibrinous, suppurative/empyema and haemorrhagic

Causes

Page 108 Carey Francis Okinda

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 14.2: Pleural Effusion overlying a pulmonary infarct

Serous, Fibrinous and Serofibrinous Pleurisy

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 infections (typhoid fever).

Produces chest pain on breathing and a pleural rub due to inflammatory

fibrinous 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 14.3: Fibrous Exudate

Page 109 Carey Francis Okinda

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 transudate fluid within

the pleural cavities. May be limited to part of a pleural cavity by pre-existing

pleural adhesions.

Causes

1) CCF

2) Renal failure

3) Liver cirrhosis

4) Meig’s syndrome

5) Pulmonary oedema

6) Primary and secondary tumours

Investigations

Chest X-ray

Obliterated costo-diaphragmatic angle

Opacities

Tracheal deviation (opposite side)

Page 110 Carey Francis Okinda

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 and Stony dull percussion

2) Features of respiratory distress

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) Pleural effusion aspiration - gross appearance, biochemistry, cytology,

microbiology and histology

2) Blood counts

3) Thoracoscopy

4) Radiology

a. Chest X-ray – erect – demonstrate pleural effusion, blunting of the

costophrenic angle

b. Ultrasound – distinguishes between pleural thickening and fluid

Page 111 Carey Francis Okinda

c. CT scan – reveals an underlying malignancy

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.

2.0 MECHANISM OF INJURY

The mechanism of injury may be categorized as low, medium, or high velocity.

Low-velocity injuries include impalement (e.g., knife wounds), which disrupts

only the structures penetrated. Medium-velocity injuries include bullet wounds

from most types of handguns and air-powered pellet guns and are

characterized by much less primary tissue destruction than wounds caused by

high-velocity forces. High-velocity injuries include bullet wounds caused by

rifles and wounds resulting from military weapons.

Blunt Thoracic Trauma

1) Fracture ribs

2) Pneumothorax

3) Haemothorax

4) Sternal fractures

5) Diaphragm

6) Lungs

7) Mediastinum

8) Heart

Penetrating Thoracic Trauma

1) Wounds

2) Viscera e.g. lungs, heart, oesophagus and thoraco-abdominal

Page 112 Carey Francis Okinda

3.0 PATHOPHYSIOLOGY

Chest injury produces many conditions including hemothorax,

hemopneumothorax, pneumothorax, diaphragmatic rupture, open

hemopneumothorax, pulmonary contusion, open pneumothorax, rib fracture,

subcutaneous emphysema, bilateral pneumothorax, open bilateral

hemopneumothorax, pneumomediastinum, thoracic wall lacerations, bilateral

hemopneumothorax, open bilateral pneumothorax, sternal fracture, bilateral

diaphragmatic rupture.

4.0 BLUNT INJURIES

4.1. 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.

4.2. 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).

4.3. Sternal Fractures

They are less common and indicate great force applied to the chest wall.

Diagnosis is made through palpation and chest radiographs.

4.4. 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.

4.5. Lungs

Deceleration produces differentiated forces across the alveolar capillary

membrane producing rupture, which leads to alveolar haemorrhage and

oedema. Coexistence shock and pulmonary under perfusion and pulmonary

neutrophils sequestration worsening the situation.

Page 113 Carey Francis Okinda

4.6. Mediastinum

Severe deceleration results in rupture of mediastinal vessels.

4.7. Heart

Contusion of the heart may occur with blunt injuries.

5.0 PENETRATING INJURIES

5.1. 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.

5.2. 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)

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 and bronchial

cancer

2) Traumatic pneumothorax - penetrating chest wounds, fracture of the ribs

and oesophageal rupture

3) Iatrogenic (therapeutic) pneumothorax

a. Subclavian cannulation

b. Positive pressure artificial ventilation

Page 114 Carey Francis Okinda

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.

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

Page 115 Carey Francis Okinda

Diagram 14.7: Safety Triangle

4.0 INVESTIGATIONS

5.0 COMPLICATIONS

Tumours of the Pleura

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.

1.0 BENIGN (SOLITARY) MESOTHELIOMA

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

a pedicle.

Macroscopy

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

What investigations will be relevant investigations?

What complications will be seen in such cases?

Page 116 Carey Francis Okinda

2.0 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 or/and by lymphatics to the hilar and

mediastinal lymph nodes

2) Distant metastasis - to the liver

3.0 INVESTIGATIONS

4.0 COMPLICATIONS

What investigations will be relevant investigations?

What complications will be seen in such cases?