Anatomy, physiology and pathology of the respiratory system (“but mainly the lungs”)

Dr Andrew Potter

Registrar

Department of Radiation Oncology

Royal Adelaide Hospital

Anatomy

Overview

Consists of nose, pharynx, larynx, trachea, bronchi, lungs

Conducting portion and respiratory portionObtains O2 and eliminates CO2 to external

environmentHelps regulate pH by adjusting rate of

removal of acid-forming CO2

Nose

External portion– Bone and cartilage, covered by skin– Mucous membrane lining– Nostrils, midline septum

Internal portion– Skull cavity inferior to cranium, superior to mouth

• Bounded by ethmoids, maxillae, palatine bone, inferior nasal conchae

– Communicates with pharynx through the choanae– Communicates with paranasal sinuses

• frontal, sphenoid, maxillary, ethmoid

– Openings of naso-lacrimal ducts, Eustachian tubes

Pharynx (throat)

Funnel-shaped tube, ~13cm longStarts at choanae (internal nares) extending

to level of cricoid cartilagePosterior to nasal cavity, oral cavity,

larynxAnterior to cervical vertebral bodiesMuscular wall lined by mucous membrane

Nasopharynx

Uppermost part of pharynxPosterior to nasal cavityExtends to plane of soft palateEustachian tube openings

– Allows air exchange to equalise ear/nose/throat pressures

Pharyngeal tonsils (adenoids) on post wall

Oropharynx

Posterior to oral cavityExtends from soft palate to level of hyoidCommon passage way for air, food, fluid -

communicates with oral cavityPalatine and lingual tonsils

Hypopharynx (laryngopharynx)

Extends downwards from hyoidContinuous with oesophagus (posteriorly)

and larynx (anteriorly)Common passage way for air and food

Larynx (voice box)

Connects pharynx with tracheaEpiglottis

– cartilage valve to separate food and airMidline in neck, anterior to C4-C6Wall consists of 9 pieces of cartilage

– 3 single• Thyroid, epiglottis and cricoid

– 3 paired• Arytenoid, corniculate, cuneiform

Vocal cords - false (ventricular) and true– Vibration of vocal cords results in phonation– Barrier against foreign bodies entering lower respiratory tract

Upper respiratory tract - summary

System of interconnected spacesTransports, filters, humidifies and warms

inspired airReceptors for smell in the nasal cavityParanasal sinuses act as resonating

chambers for speech– Also reduce weight of facial skeleton

Trachea

Tubular air passage way ~12cm long, 2.5cm diameter

Anterior to oesophagusExtends from larynx (cricoid cartilage) to

~T5Bifurcation at T5 (carina) into left and

right main bronchi

Trachea

16-20 incomplete ‘C’-shaped hyaline cartilage rings provide rigidity– Open part of each ring faces posteriorly to

oesophagus– Allows for oesophageal expansion during

swallowingTransverse smooth muscle (trachealis) and

elastic connective tissue attach open ends of cartilage rings

Trachea

Important relations– Anteriorly: thyroid isthmus, inferior thyroid

veins, sternohyoid and sternothyroid muscles, manubrium, thymus remnants

– Laterally: lobe of thyroid, carotid sheath, SVC (right), aortic arch and branches (left),

– Posteriorly: oesophagus, recurrent laryngeal nerves

Trachea

Ciliated pseudo-stratified columnar epithelium

Seromucous glands and ducts– humidify air

Cilia (‘brush border’)– Transport excess mucus,

foreign bodies upwards like an escalator

Primary (main) bronchi

Incomplete cartilage ringsStratified columnar epithelium as in tracheaRight main bronchus

– To right lung

– Shorter, wider and more vertical than left• More prone to foreign bodies lodging

Left main bronchus– To left lung

Secondary (lobar) bronchi

One for each lobe of each lung– 2 on the left

– 3 on the right

Further division into tertiary (segmental) bronchi to supply each segment of each lobe

…progressive branching until reaching bronchioles and finally terminal bronchioles and alveolar ducts

Structural features

Gradual transition from one type of airway to the next

Epithelium– Tall, pseudostratified columnar ciliated

epithelium in larynx and trachea– Simple cuboidal non-ciliated in small airways– Goblet cells (mucus secreting) gradually

disappear

Structural features

Lymphoid aggregates (MALT)– Produces IgA antibodies secreted onto mucosal surface

• protection against invading micro-organisms

Smooth muscle– Lies deep to mucosa (except in trachea)– Becomes increasingly important as airway diameter

decreases– Regulates calibre of airway and hence resistance to air

flow• Sympathetic - muscle relaxation• Parasympathetic - constriction

Structural features

Serous and mucous glands– Progressively less numerous in narrower

airwaysCartilage

– Supporting skeleton for larynx, trachea and bronchi

– Maintains patency during respiration– Gradually diminishes; absent beyond tertiary

bronchi

Lungs - gross anatomy

Paired, cone-shaped organs in thoracic cavitySeparated by heart and other mediastinal

structuresCovered by pleura

– Fibrous membrane with overlying flattened epithelium

– Outer layer - parietal pleura, attached to chest wall

– Inner layer - visceral pleural, attached to lung surface

– Potential space between the two layers (pleural cavity)

• Normally contains small amount of pleural fluid - reduces friction between surfaces during movement of respiration

Lungs - gross anatomy

Extend from diaphragm inferiorly to just above clavicles superiorly

Lies against thoracic cage (pleura, muscles, ribs) anteriorly, laterally and posteriorly

Inferior lung base is concave and fits over convexity of each hemi-diaphragm

Narrow superior apexSurface curved to match curvature of rib cage

Lungs - gross anatomy

Hilum– Medial ‘root’ of the lung– Point at which vessels, airways and lymphatics

enter and exit

Cardiac notch– Lies in medial part of left lung to

accommodate the heart

Lobes and fissures

Lungs divided into lobes by fissures– Both have an oblique fissure extending forwards and

downwards• Separates upper and lower lobes on left• Separates upper, middle and lower lobes on right

– Right lung also has horizontal fissure• Separates upper and middle lobes

Each lobe has its own secondary (lobar) bronchus– Named according to the lobe supplied

Further subdivision of each lobe into segments– …similarly supplied by a tertiary (segmental) bronchus

Lobules

Each segment has multiple small compartments - lobules– Each wrapped in connective tissue– Contains lymphatic vessel, arteriole, venule,

branch from terminal bronchiole– Terminal bronchioles subdivide into

microscopic respiratory bronchioles

Alveoli

Cup-shaped outpouchingsClustered in alveolar sacs

– Resemble microscopic bunches of grapesLined by epitheliumThin elastic basement membraneLined by type I alveolar cells with occasional type II

alveolar cells– Type II cells secrete alveolar fluid and surfactant– Surfactant acts to reduce surface tension of alveolar fluid

(like detergent), helping to keep alveoli from snapping shut

Alveoli

Alveolar macrophages (dust cells)– Phagocytes that remove dust and debris from

alveolar spaces– Derived from peripheral blood monocytes

Alveoli surrounded by capillary network to facilitate gas exchange– Single layer of endothelium and basement

membrane

Alveolar-capillary membrane

Diffusion of gas between air and circulation occurs across alveolar and capillary walls– Type I and II alveolar cells– Epithelial basement membrane beneath alveolar wall– Capillary basement membrane– Capillary endothelium

Total thickness ~0.5µmApprox 300 million alveoli in normal lungResults in large surface area (~70m2) for gas

exchange

Alveoli

Alveoli - micro

Lung - blood supply

Dual supply– Bronchial supply

• Bronchial arteries supply bronchi, airway airway walls and pleura

– Pulmonary supply• Pulmonary arteries enter at hila and branch with airways

• Deoxygenated blood from right ventricle pulmonary trunk left and right pulmonary arteries arterioles capillaries oxygenated blood to venules pulmonary veins left atrium

– Venous return is common (ie. both return via pulmonary veins)

Lymphatics

Lymphatic drainage follows vesselsParabronchial (peribronchial) lymphatics

and nodes hilar nodes mediastinal nodes pre- and para-tracheal nodes supraclavicular nodes

Physiology

Mechanics of breathing

Inspiration - an active process– Diaphragm lowers– Ribs pivot upwards

• Intercostal muscles contract• Action similar to a swinging bucket handle

– Intra-thoracic pressure lowers• Intrapleural pressure is normally 4mmHg lower than atmospheric

pressure, ‘sucking’ the lungs outwards

– Lung expands• As volume increases, pressure decreases - Boyle’s law

– Air flows from higher atmospheric pressure (760mmHg) into low pressure of the lungs (758mmHg)

Mechanics of breathing

Expiration - passive– Inspiratory muscles relax

• Ribs move downwards

• Diaphragm relaxes and its domes rise

– Surface tension of alveolar fluid causes an inward pull

– Elastic recoil of alveolar basement membranes

– Reverse pressure gradient• 762mmHg in lungs, 760mmHg atmospheric

– Gas pushed out

Respiration

External (pulmonary) respiration– exchange of O2 and CO2 between respiratory

surfaces and the blood (breathing)

Internal respiration– exchange of O2 and CO2 between the blood and

cells

Cellular respiration– process by which cells use O2 to produce ATP

External respiration

Exchange of O2 and CO2 between alveoli and blood

Partial pressure of O2 higher in alveoli (105mmHg) than blood (40mmHg) so O2 diffuses into blood

Partial pressure of CO2 higher in blood (45mmHg) than alveoli (40mmHg), so CO2 moves into alveoli in opposite direction and gets exhaled out

GasAtmospheric

airAlveolar air Exhaled air

O2

21%

159 mmHg

14%

104 mmHg

16%

120 mmHg

N2

78%

597 mmHg

75%

569 mmHg

75%

566 mmHg

CO2

0.04%

0.3 mmHg

5%

40 mmHg

4%

27 mmHg

H2O0.5%

4 mmHg

6%

47 mmHg

6%

47 mmHg

Gas partial pressures

Internal respiration

Exchange of O2 and CO2 between blood and tissues

Pressure of O2 higher in blood than tissues so O2 gets release into tissues.

Pressure of CO2 higher in tissue than in blood so CO2 diffused in opposite direction into blood.

CO2 is a waste productO2 is used in cellular respiration

Pulmonary respiration

Internal respiration

Gas transport in blood

Carbon dioxide– 70% as bicarbonate ion (HCO3

-) dissolved in plasma

– 23% bound to hemoglobin

– 7% as CO2 dissolved in plasma

Oxygen– 99% bound to hemoglobin

– 1% as O2 dissolved in plasma

Control of breathing

Respiratory centre in reticular formation of the brain stem– Medullary rhythmicity centre

• Controls basic rhythm of respiration• Inspiratory (predominantly active) and expiratory

(usually inactive in quiet respiration) neurones• Drives muscles of respiration

– Pneumotaxic area• Inhibits inspiratory area

– Apneustic area• Stimulates inspiratory area, prolonging inspiration

Regulation of respiratory centre

Chemical regulation– Most important– Central and peripheral chemoreceptors

– Most important factor is CO2 (and pH) in arterial CO2 causes in acidity of

cerebrospinal fluid (CSF) in CSF acidity is detected by pH sensors in

medulla

• medulla rate and depth of breathing

Regulation of respiratory centre

Cerebral cortex– Voluntary regulation of breathing

Inflation reflex– Stretch receptors in walls of

bronchi/bronchioles

Pathology

Benign pathology

Infective– URTI, pneumonia, bronchitis, bronchiectasis– Bacterial, viral, fungal

Vascular– Pulmonary emboli, vasculitis, pulmonary oedema

Traumatic– Pneumothorax, haemothorax

Inflammatory– Idiopathic pulmonary fibrosis, sarcoidosis

Environmental– Silicosis, asbestosis

Genetic/congenital– Cystic fibrosis

Asthma

Reversible airways obstructionCommon (10% children, 5% adults)Recurrent wheeze and breathlessnessMultiple triggers

– Allergy, infection, cold, exertion, irritation, drugs, occupational exposure

Complex chronic inflammation of bronchial mucosa

Chronic obstructive airways disease (COAD, COPD)

Combination of chronic bronchitis and emphysema– Chronic inflammation of bronchi

• Chronic cough with sputum

– Destruction of normal alveolar structure• Loss of inhibition of proteases (esp. 1-

antitrypsin)• Reduced surface area for gas exchange - fewer,

large dilated air spaces• Relative hypoxia, worse on exertion

Neoplastic diseases of the lung

Common cancerPeak incidence 40-70 years of ageClosely related to cigarette smoking and

industrial carcinogens4 main histological types

– Squamous cell carcinoma (SCC) - 50%– Small cell carcinoma (SCLCa) - 20%– Adenocarcinoma - 20%– Large cell anaplastic carcinoma (LCLCa) - 10%

Neoplastic diseases of the lung

Commonly grouped as small cell (SCLCa) and non-small cell (NSCLCa) based on natural history and response to treatment

70% arise in relation to main bronchi30% arise from peripheral airways or

alveoli

Lung cancer

Squamous cell carcinoma– Arises in metaplastic squamous epithelium that develops to

line airways against chronic exposure to irritants such as smoke

– More common in men but women catching up– Mostly central/close to carina

Adenocarcinoma– Tend to be peripherally located– Less closely associated with smoking– Equal sex distribution– 4 sub-types

• Acinar, papillary, solid, bronchoalveolar

Lung cancer - gross appearance

Central squamous cell carcinoma arising near right main bronchus

Peripheral adenocarcinoma

Lung cancer

Small cell carcinoma– Highly malignant– Centrally located– Rapidly growing– Neuro-endocrine properties and behaviours

• eg. SIADH

– Commonly present with metastatic disease– Often chemo- and radio-sensitive and

responsive but rarely curable

Lung cancer - presentation

Respiratory features– Cough (80%), haemoptysis (70%), dyspnoea (60%), chest

pain (40%), wheeze (15%)Systemic features

– Anorexia, weight loss, malaise70% present with metastatic disease

– Local spread - bronchus, mediastinum– Lymphatic spread - peribronchial, hilar nodes– Trans-coelomic spread - malignant effusion, chest wall

invasion– Haematogenous spread - brain, bone, liver, adrenal glands

Lung cancer - prognosis

Poor 5-year survival– (5-30% depending on type and stage at

presentation)NSCLCa

– 75% inoperable due to age, poor lung function or advanced stage (CT head/chest/abdo, PET, WBBS, mediastinoscopy)

– If inoperable, consider chemo-radiotherapy (radical or palliative depending on stage)

Lung cancer - prognosis

SCLCa– ~30% are ‘limited stage’ (confined to within

an achievable RT field)• Good local control with chemoRT but usually

progress to systemic disease

• Role of PCI

• Median survival 11 months

• 45% 1-year survival

– Extensive stage• Palliation only

Malignant mesothelioma

Primary neoplasm of pleura Closely related to asbestos

exposure Latent period of up to 50 years Chest pain, breathlessness Forms a thick rind around

lung and pericardium Death usually occurs within

10 months No effective treatment RT to prevent spread along

biopsy/drain tracks as needed

Respiratory system - summary

Upper respiratory tract– Series of cavities to filter, warm, humidify and

conduct air to lower respiratory tract

Lower respiratory tract– Trachea, bronchial tree deliver air to alveoli

– Gas exchange within alveoli• Diffusion down partial pressure gradients

– Dual blood supply• Unique features of pulmonary circulation

– Mechanics of breathing

Respiratory system - summary

Lungs– Paired thoracic organs

– Facilitate gas exchange

– Differences between left and right

Pathology– Huge range of benign conditions

– Neoplastic disease• SCLCa

• NSCLCa - SCC, adenoca, LCLCa

• Mesothelioma

• Poor prognosis

“The real reason dinosaurs became extinct…”