Biology of Disease

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Biology of DiseaseBiology of Disease

CH0576

Respiratory Disorders I

Dr Suad Awads.awad@northumbria.ac.ukRoom A305 Ellison’s- Ext 3816

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* Identify lung volumes & capacities

Lecture Objectives

* Explain effect of relevant pressures in pulmonary ventilation

* Discuss causes and consequence of Pneumothorax

* Explain the aetiology of obstructive lung disease

* Explain the basis of pulmonary compliance

* Discuss causes and pathological features of Asthma

* Discribe pathological features ofRespiratory Distress Syndrome

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* Spirometry: Lung Volumes & Capacities

Lecture Outline

* Pneumothorax

* Resistance to Airflow

* Chronic Obstructive Lung Diseases: Asthma

* Pulmonary Compliance: Respiratory Distress Syndrome

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Lung Volumes & Capacities

Classic Spirometer

Fig 26-1A- Boron

Spirometry: Measure air

entering or leaving lung

Change in Lung Volume

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Lung Volumes & Capacities

Fig 26-1B- Boron

TV= Tidal volumeIRV= Inspiratory Reserve

Volume

ERV= Expiratory ReserveVolume

RV= Residual Volume Air remaining in lung after max exp effort

RV= Can not be measured by a Spirometer

Max volume expired at end of quiet expiration

Max volume inhaled at end of quiet inspiration

Inspiration: Upward deflection,

Expiration: Downward deflection

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Lung Volumes & Capacities

Fig 26-1B- Boron

TLC= Total Lung CapacitySum of all 4 volumes

FRC= Functional Residual capacity

Sum of ERV + RVAir remaining after

quiet expiration

IC= Inspiratory CapacitySum of IRV + TV max inspired volume after a quiet expiration

VC= Vital CapacitySum of IRV + TV + ERV max inspired achievable tidal volume

Any capacity that includes the RV can not be measured

by a Spirometer

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Lung Volumes & Capacities

Fig 26-1B- Boron

FEV1

Forced Expiratory Volume in One Second

~ 80% VC in Healthy Young Adults

Affected in Pulmonary Disorders with increased

Airway resistance Eg Asthma

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Lung Volumes & Capacities

Volumes & Capacities Typical Ranges (L)

IRV (Inspiratory Reserve Volume) 1.9- 2.5

TV (Tidal Volume) 0.4- 0.5

ERV (Expiratory Reserve Volume) 1.1- 1.5

RV (Residual Volume) 1.5- 1.9

TLC (Total Lung Capacity) 4.9- 6.4

IC (Inspiratory Capacity) 2.3- 3.0

FRC (Functional Residual Capacity) 2.6- 3.4

VC (Vital Capacity) 3.4- 4.5

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Spirometry: FEV1/VC ratio

• FEV1 This is the forced expiratory volume in one second. It reflects airway narrowing and is

relatively independent of effort

• FVC = the forced vital capacity Normally FEV1 = 70%-80% of the FVC

FEV1 and FVC used to differentiate betweenObstructive and Restrictive patterns of lung disease

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Peak Flow Metre• Peak Expiratory Flow Rate (PEFR) is defined as the highest air flow (Vol/time) achieved at the mouth during a forced expiration

• It is a measure of the existence and severity of airflow obstruction

• The PEFR obtained by a patient is compared to that of a normative standard (use height, age, gender). It is calculated as % of the expected PEFR.

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Peak Flow Meter

Measured by modern Spirometry: Next Lecture

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FRCFunctional Residual Capacity

Determined by the lung and chest wall elastic recoils

Volume of air remaining in the lungs at the end of a quiet expiration

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Factors affecting Ispiratory & Expiratory Reserve Volumes

* Current Volume

* Lung Compliance

* Muscle Strength

* Comfort

* Posture

A measure of how easy to inflate the lungs

The greater the current volume, the less are the reserve volumes

Problems with innervation - muscle weakness

Pain (injury) limit desire or ability to make insp efforts

Recumbent position = IRV falls- Difficult for diaphragm to move abdominal contents

* Flexibility of SkeletonArthritis, Kyphoscoliosis = Reduce IRV

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Important Pressures in Pulmonary Important Pressures in Pulmonary VentilationVentilation

* Atmospheric Pressure - Barometric pressure

* Intra-alveolar Pressure - Pressure within the alveoli Fluctuates during breathing cycle: -ve inspiration, +ve expiration

* Intrapleural Pressure - Pressure inside the thoracic cavity

Less than Barometric P (-ve)

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Pneumothorax• Occurs when the Intrapleural Pressure

equilibrates with atmospheric P.As a result lungs collapse - inherent elastic recoil

• Traumatic Pneumothorax - caused by the chest wall being punctured

• Spontaneous Pneumothorax - 1. Due to a hole in the wall of the lung 2. Congenital defect in connective tissue in alveolar wall

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Traumatic

Spontaneous

COLLAPSED LUNG

Pneumothorax

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Pneumothorax

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Factors Influencing Airflow ThroughFactors Influencing Airflow Through the Lungthe Lung

Airflow (F) depends on: 1. Pressure Gradient P- Difference between atmospheric pressure and intra-alveolar pressure.

2. Resistance of Airways (R)- Determined by the radii of the airways

F is inversely related to R F = P/R

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Resistance to AirflowResistance to Airflow

F = P/R • Main determinant of resistance to airflow (R) is the RADIUS of the conducting airways • In the healthy lung the radius is relatively large and so R is low

• The airways normally offer such a low resistance that only small pressure gradients are needed for adequate airflow into the lung

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Adjustment of Airway SizeAdjustment of Airway Size

• Normally modest changes in airway size, to meet the body’s needs, are achieved through the AUTONOMIC nervous system

• In quiet respiration Parasympathetic stimulation promotes bronchiolar smooth muscle contraction causing Bronchoconstriction Maintains muscle tone in airways

• Sympathetic stimulation brings about Bronchodilation by bronchiolar smooth muscle, Decreasing airway resistance during exercise, fight or flight situations

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Pulmonary Diseases Associated Pulmonary Diseases Associated with Narrowing of the Airwayswith Narrowing of the Airways

• Increased Resistance is an extremely important impediment to airflow when airways become narrowed due to disease:

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

• COPD is a group of lung diseases including - Chronic Bronchitis, Asthma and Emphysema

• COPD is characterised by Increased Airway Resistance

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Chronic Obstructive Pulmonary DiseaseChronic Obstructive Pulmonary Disease

* Sufferers have to work harder to breathe

• F = P/RWhen resistance is increased, a larger pressure gradient is needed to maintain a normal airflow.e.g. If resistance is doubled by narrowing of airway lumens, P must be doubled through increased respiratory muscle workload

• Expiration is more difficult to accomplish than inspiration giving rise to the characteristic ‘WHEEZE’ as air is forced out of narrow airway

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Chronic Obstructive Lung Diseases (COPDs)

• Group of diseases in which there is a chronic limitation to airflow

• Flow is reduced for one of two reasons:

1. Narrowing of the Airways causing increased resistance - Asthma, Chronic Bronchitis 2. Loss of Elastic Recoil - Reduction in the outflow pressure - Emphysema

Aetiology:

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Asthma• Asthma is the Greek word for ‘Breathless’ or ‘to breathe opened mouthed’

• It is caused by Chronic Inflammatory Responses in the airways

• This leads to REVERSIBLE airway obstruction.

• It is characterised by breathlessness and wheezing

caused by generalised narrowing of intrapulmonary airways

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Causes of Asthma

Asthma is a heterogeneous disease triggered by a variety of inciting agents (Genetic + Environ)

• Extrinsic Factors Caused by Type I hypersensitivity reactions on exposure to extrinsic allergen (pollen, perfume,

dust mite, others?)

• Intrinsic Factors Non-immune trigger mechanism e.g. hormonal, stress, exercise

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AsthmaThere are three main features of asthma:

Remember: (F = P/R)

1. Muscle Spasm – Bronchospasm (Narrowing of airway lumen- increased airway R)

2. Mucus Plugging- (air trapping in distal bronchioles- increased RV, and relevant volume & capacities; eg? )

3. Mucosal Oedema- (Narrowing of lumen- increased R- increased pressure- increased work for respiratory muscles)

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Pathological Features of Asthma

* Mucosal Oedema- Inflammatory cell infiltration (Eosinophils 5%-50%)

- Basement membrane thickening

- Goblet cell and submucosal gland hyperplasia- Hypertrophy and hyperplasia of the smooth muscle in the bronchial wall

These events lead to - Airway Obstruction Bronchial Muscle Constriction Airway Congestion

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Early phase

response in asthma

SM spasm followed By inflammation

Histamine inducesSM contractionThrough H1 Rs

Lamina propria

Dust mite, pollenOther??

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Late phase response in asthma

Eosinophill Infiltration, (MBP, ECP)

Loss of Epithelial Cells

Increased mucussecretion

SM Hypersensitivity

(histamine),Infiltration ofBasophils & Neutrophils

Edema

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Pathological Features of Asthma

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Bronchioles in AsthmaBronchioles in Asthma

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Features of Asthma in Status Asthmatics

• Lungs are Overdistended - Due to trapped air• May be small areas of Atelectasis• The most striking feature is the blocking of bronchi and bronchioles with thick mucus plugs

• The mucus plugs contain - Whorls of shed epithelium - Eosinophils - Charcot - Leyden Crystals

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Charcot Leyden CrystalsCharcot Leyden Crystals

Crystallised LysophospolipaseEnzyme produced

By Eosinophils

Up to 50 mlength

Normally colourlessStains reddish by

trichrome

Indicative of a disease involving eosinophilic inflammation& proliferation

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Asthma - Clinical Course

• Severe Dyspnoea with wheezing

• Hyperinflation of lungs, with air trapped distal to the bronchi which are constricted and full of mucus (which volumes & capacities are affected?)

• This leads to Hypercapnia, acidosis and hypoxia

• Asthma tends to be severely debilitating rather than lethal

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COMPLIANCECOMPLIANCE• A factor influencing the pressure gradient P in the lung is the ELASTIC behaviour of the lung

• This affects alveolar and lung volume, and therefore the pressure gradient needed to inflate lung

• COMPLIANCE refers to how much effort is required to stretch or distend the lungs

• Specifically Compliance is a measure of the change in lung volume due to a given change in transmural pressure (The Force That Stretches the Lung)

C = V/ P

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COMPLIANCECOMPLIANCE

• A HIGHLY compliant lung stretches further for a given increase in pressure than does a LESS compliant lung (eg inflating a very flexible Vs stiff balloon)

• A LESS compliant lung will require MORE Effort (P) to produce a given degree of inflation

• A POORLY compliant lung is referred to as a ‘STIFF LUNG’

• Compliance is reduced in pulmonary diseases e.g. FIBROSIS of the lung

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Factors Affecting Pulmonary ComplianceFactors Affecting Pulmonary Compliance

Pulmonary compliance depends on various factors:

1. Highly Elastic Connective Tissue

2. Alveolar Surface Tension:- due to a

thin liquid film lining each alveolus.

It resists any force that increases

surface area (thus OPPOSES expansion)

3. Pulmonary Surfactant:- Surface Active Agent - detergent !

produced by TYPE II alveolar cells, decreases surface

tension (70 dynes/cm Vs 25 dynes/cm)

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Pulmonary CompliancePulmonary Compliance

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Effect of Pulmonary SurfactantEffect of Pulmonary Surfactant

• It REDUCES the surface tension and contributes to lung stability

• It acts by interspersing water molecules lining the alveolus, which reduces surface tension

Benefits of Reducing Surface Tension:

a) Increases pulmonary compliance - thus reducing the effort needed to inflate the lungs

b) It stabilises the alveoli so they do not collapse at end of expiration

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Newborn Respiratory Distress SyndromeNewborn Respiratory Distress Syndrome

• Surfactant produced by 34th wk gestation * Premature infants- Deficiency in lung surfactant

leads to Newborn Respiratory Distress Syndrome

• Very strenuous inspiratory efforts are required to overcome the high surface tension in the alveoli The lungs are Poorly Compliant

• It may require transmural pressure gradients of 20-30 mm Hg (normally 4-6 mm Hg) to overcome the tendency of the lungs to collapse

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NEWBORN RDS

• The problem is compounded as the newborn’s muscles are still very weak

• Deficiency in surfactant leads to alveolar instability and severe respiratory failure

• Life threatening condition

• Newborn RDS can be treated by: a) Artificially increasing atmospheric pressure b) Treating with exogenous surfactant

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Useful Textbooks

Rhoades & Bell, 3rd ed. Medical Physiology: Principles of Clinical Medicine. LWW

Boron & Boulpeap, 2nd ed. Medical Physiology: Saunders