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Respiratory System General Introduction - Pathology (view source)
Revision as of 15:34, 31 July 2008
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|backcolour = D1EEEE
|linkpage =Cardiorespiratory System - Pathology
|linktext =Cardiorespiratory System
|maplink = Cardiorespiratory System (Content Map) - Pathology
|pagetype =Pathology
|sublink1=Respiratory System - Pathology
|subtext1=RESPIRATORY SYSTEM
}}
<br>
==Invasion of respiratory system==
*The most common respiratory diseases seen in domestic animals are those caused by microbiological agents (particularly viruses, bacteria and mycoplasma), parasites, secondary neoplasia and cardiovascular abnormalities.
*There are three main routes of invasion into the respiratory tract: - AEROGENOUS (via airways), HAEMATOGENOUS (via blood), TRANSCOELOMIC (direct).
===Aerogenous===
*Infection reaches the lung as inhaled droplets or larger food particles or fluid
*Particles > 10um will usually be deposited above the larynx
*Many smaller particles will also interact with the mucosa of the nasal cavity and nasopharynx
*Hence many viral and bacterial diseases initially replicate in the epithelium and lymphoid tissue of the upper respiratory tract - before either spreading systemically or being redistributed to the lower respiratory tract
*As particle size decreases, aerodynamic properties increase hence an increased proportion of particles will pass down the respiratory tract
*Irritant/ infectious particles that are ~ 1-2 um in size will deposit mostly at the bronchiolar-alveolar junction
*Due to mechanics of air flow in this area:
**Total air space area suddenly increases -> air stream velocity rapidly drops -> time for particles to settle by gravity
***Major reason why the bronchiolar-alveolar junction is vulnerable to damage caused by inhaled irritants
===Haematogenous===
*Distribution tends to be to '''caudal lobes'''
*But all lobes are affected when number of particles is high
*There is no orientation on the airways
===Transcoelomic===
*Infection via extension from pleura or mediastinum, or traumatic penetration from chest wall (e.g. bite), diaphragm (e.g. [[Forestomach - Inflammation#Traumatic Reticulitis|bovine traumatic reticulitis]]) or oesophagus (e.g. foreign body).
==[[General Pathology - Healing and Repair#Repair in the Respiratory Tract|Repair in the respiratory tract]]==
==Functional anatomy==
===Mucosa===
*Mucosal epithelium
**Nares and epiglottis- stratified squamous
**Nasal cavity, paranasal sinuses, larynx, trachea - pseudostratified, columnar, cilliated, olfactory
*Submucosa
**Submucosal glands
**Lymphoid tissue
*Blood vessels, lymphatics and nerves
**Very rich blood supply to nasal mucosa
===Nasal chambers and turbinates===
*Scrolls of turbinate bone - increase surface area
*Arrangements vary with species
*Remove particels above 10-20um in size
*Humidifies and warms incoming air
*Detects noxious irritants
===Nasal septum===
*Full length of nasal chamber in horses
**2 openings into pharynx
*Partial length in other species
**Single opening into pharynx
===Sinuses===
*Size, arrangement and number vary with species
*Poorly developed in carnivores
**Poor communication of frontal sinus in cats with nasal cavity
***Predisposed to frontal sinus bacterial infections
**Maxillary sinus opening very large - 'maxillary recess'
***Maxillary sinus infections very uncommon in carnivores
**Highly developed in [[Hindgut Fermenters - Horse - Anatomy & Physiology|horses]]
**Slit-like, high openings in horses
**Predisposed to bacterial infections
**Cheek teeth embedded within the maxillary sinuses
**Maxillary sinusitis secondary to tooth root abscesses
===Nasopharynx===
*Ciliated pseudostratified epithelium
*Many lymphoid nodules in submucosa
===Larynx===
*Epiglottis prevents entry of food into the trachea
===Guttural pouch===
*Horses
**Diverticulaof the eustachian tubes with thin slit-like openings (ostia) at the rostroventral aspect into the pharynx
**Ostia open during geglutition
**Mucous secretions drain out of the pouch when the horse lowers its head
**Each pouch is divided into lateral and medial compartments by the stylohyoid bone
**Medial compartment bordered by:
***Internal carotid artery
***Cranial sympathetic nerves
***Cranial cervical ganglion
***Cranial nerves: glossopharyngeal (IX), vagus (X), accessory (XII) and hypoglossal (XII)
**Lateral compartment bordered by:
***External carotid and maxillary arteries
***Cranial nerve: facial (VII)
**Lined by respiratory epithelium
===Larynx===
*Stratified squamous epithelium and ciliated respiratory epithelium
*Supported by cartilage
===Trachea===
[[Image:Trachea epithelium.jpg|right|thumb|100px|<small><center>Epithelium of trachea (Courtesy of RVC Histology Images)</center></small>]]
*Most domestic animals - pseudostratified epithelium, ciliated, non-ciliated and mucous cells
===Bronchi===
[[Image:Bronchus.jpg|right|thumb|100px|<small><center>Bronchus (Courtesy of RVC Histology Images)</center></small>]]
*Cartilage, smooth muscle seromucous glands, and ciliated epithelium with goblet cells.
*Defence mechanisms therefore are the same as the URT mucosa but also include:
**Coughing
**Bronchial associated lymphoid tissue (BALT) covered by M cells (microfold cells) where there is professional APC and lymphocytes trafficking.
===Bronchioles===
[[Image:Bronchus, bronchiole, blood vessel.jpg|right|thumb|100px|<small><center>Bronchus, bronchiole, blood vessel (Courtesy of RVC Histology Images)</center></small>]]
*The bronchioles form a transition zone between the airway conducting system and the alveoli (gas-exchange region).
*A number of anatomical features of the bronchioles render them vulnerable to insult.
**Diminished mucociliary defences due to:
**No goblet cells in the mucosal epithelium
**No submucosal seromucous glands (except in the cat)
**Smaller and fewer cilia present on the respiratory epithelium
**No supporting cartilage rings
**Clara cells (non-cilliated columnar epithelial cells) are present that are metabolically active (rich in cytochrome p450 enzymes ie: just like the liver), with a role in bioactivation or detoxification of metabolites/drugs.
**Can produce reactive metabolites that result in further pulmonary damage eg: fog fever in cattle
**Alveolar macrophages and neutrophils accumulate at the terminal bronchioles
**Activation during inflammation and may result in release of free radicals, resulting in oxidative damage to adjacent bronchiolar cells.
*More prone to obstruction than bronchi when inflamed
===Lungs===
[[Image:Lung scanning electron micrograph.jpg|right|thumb|100px|<small><center>Sheep lung - scanning electron micrograph (Courtesy of RVC Histology Images)</center></small>]]
[[Image:Alveoli.jpg|right|thumb|100px|<small><center>Alveoli (Courtesy of RVC Histology Images)</center></small>]]
*The lung receives half of the cardiac output and must rapidly exchange gases with this large blood volume through a vast alveolar membranous surface
*This makes the lung vulnerable to circulatory disturbances, most notably [[Lungs - circulatory#Pulmonary oedema|pulmonary oedema]]
*Normally, mechanisms are in place to protect the lung from the entry of circulatory fluid into alveolar spaces
**Alveolar epithelium and its intercellular junctions are highly impermeable to fluid and seal off alveolar spaces
**Interstitium of alveolar septa is at lower pressure than intra-alveolar pressure
**Interstitial pressure becomes increasingly sub-atmospheric (negative) toward the fascia surrounding vessels and airways and towards the pulmonary hilus
*The net effect is that liquid moves from the alveolar interstitum towards lymphatics in the fascia and then the hilus of the lung and mediastinum
===Pleural membranes===
*Lined with [[Mesothelial cells|mesothelial cells]]
==Defense mechanisms==
===Particle deposition===
*Coiled nature of turbinates promotes turbulent airflow and impaction of large particles >10 μm in diameter onto the nasal mucosa
===Mucociliary escalator===
*Extends from terminal bronchioles to larynx
*Cilia on the respiratory epithelium beat in a co-ordinated manner
**Cilia beat in a caudal direction in nasal cavity
**Cilia beat in a cranial direction in trachea and lower airways
**Mucus is swallowed when it reaches the nasopharynx
**Constant movement reduces chances that pathogens can adhere to the respiratory epithelium
===Mucus===
*Produced by the goblet cells of the respiratory epithelium and the submucosal glands with contribution from lacrimal glands draining into the nose
*Traps particles for transportation away and subsequent swallowing
*Physical barrier against mucosal damage
*Prevents dessication of the mucosal epithelium
*Contains antimicrobial substances
*Immunoglobulin - IgA
**IgA produced by mucosal plasma cells
**IgA can attach to specific pathogen antigens (viruses, bacteria) trapping them in the mucus for clearance
*Lysosyme
**Direct action on bacterial cell walls
**Lactoferrin
***Inhibits bacterial growth as sequesters iron, an essential co-factor for many bacteria
*This mucous blanket is contributed to by the secretions of the Clara cells in the terminal and respiratory bronchioles
*Also contained in these secretions in the respiratory tract are: IgA, IgG, and Interferon
*At all levels of the tract, and especially at bifurcations, there are subepithelial leukocytes which have the potential to develop into lymphoid follicles under a persistent antigenic challenge
===Alveolar macrophages===
[[Image:Alveolar macrophages.jpg|right|thumb|100px|<small><center>Alveolar macrophages (Courtesy of RVC Histology Images)</center></small>]]
*Phagocytes resident within the alveolus
*There is normally one sentinel macrophage per alveolus and they ingest particles which reach the alveolus
*When activated by such irritants, they have increased phagocytic and bactericidal capability and are able to recruit further [[Macrophages - Anatomy & Physiology|macrophages]] ([[Monocytes - Anatomy & Physiology|monocytes]] from the blood), and also to attract [[Neutrophils - Anatomy & Physiology|neutrophils]] and other [[Leukocytes - Anatomy & Physiology|leukocytes]] to the site
*Removal of phagocytosed irritants may be via the mucociliary escalator or carried to the interstitium for sequestration in the connective tissue
===Commensal bacteria===
*The normal bacterial flora of the nasal cavity, pharynx, larynx and proximal portion of the trachea compete with potentially pathogenic bacteria and help to prevent their colonisation (competitive exclusion).
*The airway environment distal to the mid-portion of the trachea is effectively sterile.
*Gram positive bacteria
===Reflexes===
*Sneezing
*Coughing
|backcolour = D1EEEE
|linkpage =Cardiorespiratory System - Pathology
|linktext =Cardiorespiratory System
|maplink = Cardiorespiratory System (Content Map) - Pathology
|pagetype =Pathology
|sublink1=Respiratory System - Pathology
|subtext1=RESPIRATORY SYSTEM
}}
<br>
==Invasion of respiratory system==
*The most common respiratory diseases seen in domestic animals are those caused by microbiological agents (particularly viruses, bacteria and mycoplasma), parasites, secondary neoplasia and cardiovascular abnormalities.
*There are three main routes of invasion into the respiratory tract: - AEROGENOUS (via airways), HAEMATOGENOUS (via blood), TRANSCOELOMIC (direct).
===Aerogenous===
*Infection reaches the lung as inhaled droplets or larger food particles or fluid
*Particles > 10um will usually be deposited above the larynx
*Many smaller particles will also interact with the mucosa of the nasal cavity and nasopharynx
*Hence many viral and bacterial diseases initially replicate in the epithelium and lymphoid tissue of the upper respiratory tract - before either spreading systemically or being redistributed to the lower respiratory tract
*As particle size decreases, aerodynamic properties increase hence an increased proportion of particles will pass down the respiratory tract
*Irritant/ infectious particles that are ~ 1-2 um in size will deposit mostly at the bronchiolar-alveolar junction
*Due to mechanics of air flow in this area:
**Total air space area suddenly increases -> air stream velocity rapidly drops -> time for particles to settle by gravity
***Major reason why the bronchiolar-alveolar junction is vulnerable to damage caused by inhaled irritants
===Haematogenous===
*Distribution tends to be to '''caudal lobes'''
*But all lobes are affected when number of particles is high
*There is no orientation on the airways
===Transcoelomic===
*Infection via extension from pleura or mediastinum, or traumatic penetration from chest wall (e.g. bite), diaphragm (e.g. [[Forestomach - Inflammation#Traumatic Reticulitis|bovine traumatic reticulitis]]) or oesophagus (e.g. foreign body).
==[[General Pathology - Healing and Repair#Repair in the Respiratory Tract|Repair in the respiratory tract]]==
==Functional anatomy==
===Mucosa===
*Mucosal epithelium
**Nares and epiglottis- stratified squamous
**Nasal cavity, paranasal sinuses, larynx, trachea - pseudostratified, columnar, cilliated, olfactory
*Submucosa
**Submucosal glands
**Lymphoid tissue
*Blood vessels, lymphatics and nerves
**Very rich blood supply to nasal mucosa
===Nasal chambers and turbinates===
*Scrolls of turbinate bone - increase surface area
*Arrangements vary with species
*Remove particels above 10-20um in size
*Humidifies and warms incoming air
*Detects noxious irritants
===Nasal septum===
*Full length of nasal chamber in horses
**2 openings into pharynx
*Partial length in other species
**Single opening into pharynx
===Sinuses===
*Size, arrangement and number vary with species
*Poorly developed in carnivores
**Poor communication of frontal sinus in cats with nasal cavity
***Predisposed to frontal sinus bacterial infections
**Maxillary sinus opening very large - 'maxillary recess'
***Maxillary sinus infections very uncommon in carnivores
**Highly developed in [[Hindgut Fermenters - Horse - Anatomy & Physiology|horses]]
**Slit-like, high openings in horses
**Predisposed to bacterial infections
**Cheek teeth embedded within the maxillary sinuses
**Maxillary sinusitis secondary to tooth root abscesses
===Nasopharynx===
*Ciliated pseudostratified epithelium
*Many lymphoid nodules in submucosa
===Larynx===
*Epiglottis prevents entry of food into the trachea
===Guttural pouch===
*Horses
**Diverticulaof the eustachian tubes with thin slit-like openings (ostia) at the rostroventral aspect into the pharynx
**Ostia open during geglutition
**Mucous secretions drain out of the pouch when the horse lowers its head
**Each pouch is divided into lateral and medial compartments by the stylohyoid bone
**Medial compartment bordered by:
***Internal carotid artery
***Cranial sympathetic nerves
***Cranial cervical ganglion
***Cranial nerves: glossopharyngeal (IX), vagus (X), accessory (XII) and hypoglossal (XII)
**Lateral compartment bordered by:
***External carotid and maxillary arteries
***Cranial nerve: facial (VII)
**Lined by respiratory epithelium
===Larynx===
*Stratified squamous epithelium and ciliated respiratory epithelium
*Supported by cartilage
===Trachea===
[[Image:Trachea epithelium.jpg|right|thumb|100px|<small><center>Epithelium of trachea (Courtesy of RVC Histology Images)</center></small>]]
*Most domestic animals - pseudostratified epithelium, ciliated, non-ciliated and mucous cells
===Bronchi===
[[Image:Bronchus.jpg|right|thumb|100px|<small><center>Bronchus (Courtesy of RVC Histology Images)</center></small>]]
*Cartilage, smooth muscle seromucous glands, and ciliated epithelium with goblet cells.
*Defence mechanisms therefore are the same as the URT mucosa but also include:
**Coughing
**Bronchial associated lymphoid tissue (BALT) covered by M cells (microfold cells) where there is professional APC and lymphocytes trafficking.
===Bronchioles===
[[Image:Bronchus, bronchiole, blood vessel.jpg|right|thumb|100px|<small><center>Bronchus, bronchiole, blood vessel (Courtesy of RVC Histology Images)</center></small>]]
*The bronchioles form a transition zone between the airway conducting system and the alveoli (gas-exchange region).
*A number of anatomical features of the bronchioles render them vulnerable to insult.
**Diminished mucociliary defences due to:
**No goblet cells in the mucosal epithelium
**No submucosal seromucous glands (except in the cat)
**Smaller and fewer cilia present on the respiratory epithelium
**No supporting cartilage rings
**Clara cells (non-cilliated columnar epithelial cells) are present that are metabolically active (rich in cytochrome p450 enzymes ie: just like the liver), with a role in bioactivation or detoxification of metabolites/drugs.
**Can produce reactive metabolites that result in further pulmonary damage eg: fog fever in cattle
**Alveolar macrophages and neutrophils accumulate at the terminal bronchioles
**Activation during inflammation and may result in release of free radicals, resulting in oxidative damage to adjacent bronchiolar cells.
*More prone to obstruction than bronchi when inflamed
===Lungs===
[[Image:Lung scanning electron micrograph.jpg|right|thumb|100px|<small><center>Sheep lung - scanning electron micrograph (Courtesy of RVC Histology Images)</center></small>]]
[[Image:Alveoli.jpg|right|thumb|100px|<small><center>Alveoli (Courtesy of RVC Histology Images)</center></small>]]
*The lung receives half of the cardiac output and must rapidly exchange gases with this large blood volume through a vast alveolar membranous surface
*This makes the lung vulnerable to circulatory disturbances, most notably [[Lungs - circulatory#Pulmonary oedema|pulmonary oedema]]
*Normally, mechanisms are in place to protect the lung from the entry of circulatory fluid into alveolar spaces
**Alveolar epithelium and its intercellular junctions are highly impermeable to fluid and seal off alveolar spaces
**Interstitium of alveolar septa is at lower pressure than intra-alveolar pressure
**Interstitial pressure becomes increasingly sub-atmospheric (negative) toward the fascia surrounding vessels and airways and towards the pulmonary hilus
*The net effect is that liquid moves from the alveolar interstitum towards lymphatics in the fascia and then the hilus of the lung and mediastinum
===Pleural membranes===
*Lined with [[Mesothelial cells|mesothelial cells]]
==Defense mechanisms==
===Particle deposition===
*Coiled nature of turbinates promotes turbulent airflow and impaction of large particles >10 μm in diameter onto the nasal mucosa
===Mucociliary escalator===
*Extends from terminal bronchioles to larynx
*Cilia on the respiratory epithelium beat in a co-ordinated manner
**Cilia beat in a caudal direction in nasal cavity
**Cilia beat in a cranial direction in trachea and lower airways
**Mucus is swallowed when it reaches the nasopharynx
**Constant movement reduces chances that pathogens can adhere to the respiratory epithelium
===Mucus===
*Produced by the goblet cells of the respiratory epithelium and the submucosal glands with contribution from lacrimal glands draining into the nose
*Traps particles for transportation away and subsequent swallowing
*Physical barrier against mucosal damage
*Prevents dessication of the mucosal epithelium
*Contains antimicrobial substances
*Immunoglobulin - IgA
**IgA produced by mucosal plasma cells
**IgA can attach to specific pathogen antigens (viruses, bacteria) trapping them in the mucus for clearance
*Lysosyme
**Direct action on bacterial cell walls
**Lactoferrin
***Inhibits bacterial growth as sequesters iron, an essential co-factor for many bacteria
*This mucous blanket is contributed to by the secretions of the Clara cells in the terminal and respiratory bronchioles
*Also contained in these secretions in the respiratory tract are: IgA, IgG, and Interferon
*At all levels of the tract, and especially at bifurcations, there are subepithelial leukocytes which have the potential to develop into lymphoid follicles under a persistent antigenic challenge
===Alveolar macrophages===
[[Image:Alveolar macrophages.jpg|right|thumb|100px|<small><center>Alveolar macrophages (Courtesy of RVC Histology Images)</center></small>]]
*Phagocytes resident within the alveolus
*There is normally one sentinel macrophage per alveolus and they ingest particles which reach the alveolus
*When activated by such irritants, they have increased phagocytic and bactericidal capability and are able to recruit further [[Macrophages - Anatomy & Physiology|macrophages]] ([[Monocytes - Anatomy & Physiology|monocytes]] from the blood), and also to attract [[Neutrophils - Anatomy & Physiology|neutrophils]] and other [[Leukocytes - Anatomy & Physiology|leukocytes]] to the site
*Removal of phagocytosed irritants may be via the mucociliary escalator or carried to the interstitium for sequestration in the connective tissue
===Commensal bacteria===
*The normal bacterial flora of the nasal cavity, pharynx, larynx and proximal portion of the trachea compete with potentially pathogenic bacteria and help to prevent their colonisation (competitive exclusion).
*The airway environment distal to the mid-portion of the trachea is effectively sterile.
*Gram positive bacteria
===Reflexes===
*Sneezing
*Coughing