Module 2 Respiratory Flashcards
Skull osteology
Ethmoid bone - Superior midline nasal septum
Frontal bone - Front of head
Mandible - Jaw
Maxilla - Lower mouth and Above mouth
Sphenoid bone - Behind the eyes and nose
Nasal bones - Top of nose
Occipital bone - Back of head
Palatine bones - Back of mouth
Parietal bones - Top of head
Temporal bones - Bottom of skull
Vomer - inferior midline nasal septum
Zygomatic bones - outside cheeks
GEM Upper Respiratory Tract - Part 1
Anatomy of the nasal cavities
The anterior openings (the nares) are formed by the two nostrils.
The posterior openings (called the choanae) open into the nasopharynx
The floor of the nasal cavity is formed by the maxillary bone and the palatine bone, which form the hard palate (ie, roof of the oral cavity)
The medial walls are formed by a midline nasal septum made of ethmoid and vomer bone(inferior to ethmoid) (posteriorly) and septal cartilage (anteriorly).
The lateral walls are formed by a number of the bones of the skull, by cartilage and soft tissues.
Three nasal conchae (curled shelves of bone – also called the ‘turbinates’) protrude from lateral walls – superior, middle and inferior.
The conchae create 4 air channels/meatuses, which are contained within the respiratory regions of the nasal cavity.
What is the function of the Conchae/Turbinates?
increase the surface area of contact between tissues of the lateral wall of the nasal cavity and the respired air.
This improves the filtration, heating and humidification of inspired air
What covers the nasal cavity?
thick, vascular, glandular mucosal layer with pseudostratified ciliated columnar respiratory epithelium. This contains erectile tissue with venous sinusoids which will intermittently fill with blood.
What are the paranasal sinuses?
Frontal, Ethmoidal, Maxillary, Sphenoidal
What are the function of the sinuses?
Lighten the weight of the head, humidify and heat inhaled air, increase the resonance of speech.
What can cause the spread of disease from sinuses?
The close anatomical relations of the sinuses to the orbit, the meninges (linings of the brain) and the brain and the thin bony walls do make this possible.
What epithelium lines the sinuses?
Ciliated, mucous secreting respiratory epithelium
How are Pituitary adenomas removed?
Most pituitary tumours can be removed trans-sphenoidally.
The approach is through the sphenoid sinus.
What blood supplies the nasal cavities and the air sinuses
The arterial blood supply to the nasal cavities and paranasal sinuses come from branches of the facial, maxillary and ophthalmic arteries (from the internal and external carotid arteries)
What blood supplies the ethmoidal and frontal sinuses
Branches from the ophthalmic artery (a branch of the ICA) – also supply the ethmoidal and frontal sinuses
What blood supply supplies the lip and anterior nasal cavity?
Branches from the facial artery (a branch of the ECA) – supply lip and anterior nasal cavity
What blood supply supplies the nasal mucosa and also supplies the maxillary and sphenoidal sinuses?
Branches from the maxillary artery (a branch of the ECA) – form the main supply to nasal mucosa and also supplies the maxillary and sphenoidal sinuses
Where is a common site of nose bleeds?
An anastomotic plexus of arteries, lies on the anterior cartilaginous septum – this is a common site for nosebleeds (epistaxis)
Sensory nerve supply to the paranasal air sinuses?
The trigeminal nerve (CN V) is the major general sensory cranial nerve of the head and it has 3 major divisions.
The ophthalmic division provides the sensory supply to the upper part of the face, the maxillary division the middle part and the mandibular division to the lower part of the face.
The frontal sinuses are, therefore, supplied by the ophthalmic (V1) division
The ethmoidal and sphenoidal sinuses and nasal cavity are supplied by both the ophthalmic (V1) and maxillary (V2) divisions
The maxillary sinuses are supplied solely by the maxillary (V2) division
Nerve supply to the nasal cavities
Olfactory nerve (CN I) which is responsible for olfaction (our sense of smell)
The mucous producing cells of the nasal mucosa are supplied by parasympathetic neurons and the smooth muscle walls of blood vessel in the respiratory epithelium are supplied by sympathetic neurons which are both carried in the maxillary (CN V2) division of the trigeminal nerves (CN V).
General sensation - touch, pain and temperature from the nasal mucosa is carried by branches of the ophthalmic (CN V1) and maxillary (CN V2) divisions of the trigeminal nerve (CN V).
Describe apertures in the nasal cavity
Blood vessels, nerves and drainage enter and exit the nasal cavity via apertures in the bones of the skull.
List the main apertures in the nasal cavity
Cribriform plate – fibres of the olfactory nerve (CN I) and the branches from the ophthalmic vessels pass through here
Sphenoid sinus drains into the sphenoethmoidal recess above the superior concha
Maxillary, ethmoidal and frontal sinuses mainly drain into the middle meatus
Maxillary, ethmoidal and frontal sinuses mainly drain into the middle meatus
Why might an infection persist in the maxillary sinus?
The sinuses also drain into the nasal cavity.
All will drain assisted by gravity (except for the maxillary sinuses – this makes these sinuses more prone to infections).
Infections result in swollen mucosa, blocked drainage holes and subsequent pressure (and pain) on the nearby structures.
Explain the patterns of pain referral from the paranasal air sinuses.
Irritation of sensory nerves by inflammatory mediators, pressure changes, and a blocked non-draining sinus may present with pain which is felt away from the site of the actual pathology.
What is Sinusitis?
Pain over the site of an infected sinus is common in sinusitis (inflammation of the lining of the nasal cavity and the sinuses).
The infection may be viral or bacterial.
Symptoms of sinusitis
Nasal blockage, congestion, obstruction—essential for diagnosis
Nasal discharge (anterior rhinorrhoea or post-nasal drip)—essential for diagnosis
Reduced sense of smell (hyposmia)
Describe two pain patterns of sinusitis - referred pain.
The headache may result from frontal sinusitis due to compression/irritation of branches from the ophthalmic (CN V1) division of the trigeminal nerve (CN V).
Toothache may occur with acute maxillary sinusitis due to compression/irritation of branches from the maxillary (CN V2) division of the trigeminal nerve (CN V).
What does the pharynx do?
Conducts air to the larynx, trachea, and lungs
In breathing, air may flow through either the nose or the mouth but it always flows through the pharynx
Directs food to the oesophagus
During swallowing, the pharynx changes from an airway to a food channel
What is the pharynx?
Thepharynxis a Musculo membranous tube - extends from the choanae (posterior openings of the nasal cavity) to the oesophagus, which starts at the cricoid cartilage (vertebral level C6)
What are the subdivisions of the pharynx
Nasopharynx – the nasal cavities open into here
Oropharynx – the oral cavity opens into here
Laryngopharynx – the laryngeal inlet opens into here
What are the muscles of the pharynx and their innervation?
3 circular constrictors
Superior - Vagus
Middle - Vagus
Inferior - Vagus
3 longitudinal elevators
Salpingopharyngeus - Vagus
Palatopharyngeus - Vagus
Stylopharyngeus - Glossopharyngeal
Tensor veli palatini - Mandibular division of trigeminal nerve (CN V3)
Levator veli palatini - Vagus
^^^Two other muscles shown here attach to the soft palate – one tenses the soft palate and one elevates the soft palate.
Structures of the Nasophayrnx
Pharyngotympanic tube (auditory tube)
Salpingopharyngeus, palatopharyngeus, stylopharyngeus muscles
Superior, middle and inferior pharyngeal constrictor muscles
Pharyngeal (adenoid) tonsil
The floor of the nasopharynx (soft palate) can raise and lower
Structures of the Oropharynx
Begins at the pharyngeal isthmus
The posterior tongue forms the anterior oropharynx
Palatoglossal arch
Palatopharyngeal arch
Palatine tonsil
Structures of the Laryngopharynx
The laryngeal inlet opens into the anterior laryngopharynx
Epiglottis
Laryngeal inlet
Opening of oesophagus
Nerve supply to the Pharynx: Sensory
Nasopharynx – the maxillary (V2) division of the trigeminal nerve (CN V)
Oropharynx - glossopharyngeal nerve (CN IX) + Stylopharyngeus muscle
Laryngopharynx – the vagus nerve (CN X) + taste sensation from the pharynx
Motor supply to the pharynx?
Motor supply to the pharynx is mostly by the Vagus nerve (CN X). However, each region of the pharynx has a different sensory innervation
Referred pain from the Pharynx examples
A lesion in the pharynx but the pain may be felt around the external ear.
This happens because part of the skin of the outer ear is supplied by a branch of the Vagus nerve (CN X) (the auricular branch).
The laryngopharynx is also supplied by a branch of the Vagus nerve (CN X) – the superior laryngeal nerve
Sensory neurons from both the vagal nerve branches synapse in the same place in the medulla of the brain – the brain can get ‘confused’ as to where the pain is coming from and interprets that it is coming from a lesion of the skin of the ear rather than from the laryngopharynx.
Loss of the sensory or motor nerve supply to half of the pharynx (e.g. as a result of stroke) results in:
Diminished gag reflex – Due to glossopharyngeal nerve (CN IX) sensory loss & Vagus nerve (CN X) motor loss
Poor swallowing reflex – because of pharyngeal and laryngeal muscle paralysis due to Vagus nerve (CN X) loss
What is the larynx responsible for?
An air passage – part of the respiratory viscera
A sphincter – to prevent aspiration (inhalation) of foods and liquids
An organ of phonation - Production of sounds / voice
Raises intra-abdominal pressure - Valsalva manoeuvre
What is the larynx?
It is a hollow tube formed by a series of nine cartilages interconnected by the ligaments and fibrous membranes.
It moves up and down during swallowing under the action of a number of extrinsic muscles (i.e., the muscles that originate from neighbouring structures and insert into the larynx)
Intrinsic muscles (which have their origin and insertion within larynx) move the vocal folds and modify the laryngeal inlet.
Where is the larynx?
The larynx is suspended from the hyoid bone
Describe the hyoid bone?
The hyoid bone is attached to the:
Floor of the oral cavity above
The larynx below
The pharynx posteriorly
The hyoid bone is suspended from the styloid process of the temporal bone of the skull by the stylohyoid ligament
A number of muscles attach to the hyoid, such as the middle pharyngeal constrictor.
Describe the larynx membranes
The larynx is joined to surrounding structures by a number of membranes:
The thyrohyoid membrane is a broad, fibroelastic membrane attached to the thyroid cartilage and hyoid bone
The cricothyroid membrane attaches to the thyroid and cricoid cartilage and to the vocal processes of the arytenoid cartilages
The upper free margin of the cricothyroid membrane forms the vocal ligaments
Describe the larynx cartilages
The laryngeal skeleton is nine cartilages: the thyroid cartilage, cricoid cartilage, epiglottis, arytenoid cartilages, corniculate cartilages, and cuneiform cartilages.
The first three are unpaired cartilages, and the latter three are paired cartilages.
The thyroid cartilage pivots forward and backwards at the cricoids synovial joints.
What forms the true vocal folds
The vocal ligaments (which are elastic) form the skeleton of the true vocal folds (they extend from the vocal process of the arytenoid cartilage to the thyroid cartilage).
The true vocal folds are formed by the mucosal covering and the underlying vocal ligaments.
The vocal folds can be abducted and adducted by the intrinsic muscles of the larynx.
Moving vocal folds opens and closes the rima glottidis
What is unique about the vocal ligaments?
The vocal ligaments are covered with a non-keratinized, stratified squamous epithelial mucosa (ie NOT the usual respiratory mucosa usually found in the larynx) - this protects the tissue from the effects of the considerable mechanical stresses that act on the surfaces of the vocal folds.
What controls the glottis movements?
The primary muscle which opens the glottis (by Abducting the vocal folds) is the posterior cricoarytenoids – if these are paralysed then asphyxiation can result as the airway will be unable to open!
The Larynx: Motor supply to the intrinsic muscles
Motor supply: All the intrinsic muscles of the larynx are supplied by the Vagus nerve (CN X)
BUT - by the different branches of it.
All the muscles EXCEPT CRICOTHYROID are supplied by the recurrent laryngeal branch of the Vagus nerve (CN X)
At the arch of the aorta (on the left side only) the Vagus nerve (CNX) gives off the recurrent laryngeal branch which then ascends back up the left side of the neck to innervate the intrinsic muscles of the larynx
At the right sub-clavian artery (on the right side only) the Vagus nerve (CN X) gives off the recurrent laryngeal branch which then ascends back up the right side of the neck to innervate the intrinsic muscles of the larynx
Clinical example of the Recurrent Laryngeal Nerve pathology (RLNs)
Tumours of the apex of the right lung (Pancoast Tumours) may compress the right recurrent laryngeal nerve (as it is given off at the sub-clavian artery)
Results in a hoarse voice and right vocal cord palsy
Surgery to the left lung (lobectomy or pneumonectomy) or tumours involving the hilum of the lung may result in injury/compression to the left recurrent laryngeal nerve (as it is given off at the aortic arch)
Results in a hoarse voice and left vocal cord palsy
Bilateral lesions of RLNs:
Thyroid surgery
Cervical spinal surgery
Viral infection
The patient may have a near normal voice because the vocal cords will lie close to the midline (see image)
The voice will be minimally affected
HOWEVER, the airway will be very compromised, because abduction of the vocal cords will not be possible on either side
Patients can present with respiratory distress resulting in hypoxia, respiratory arrest and death!
They may require urgent tracheotomy
Three regions of the temporal bone
Squamous part
Petro-mastoid part
Tympanic part
What are the auditory ossicles? and where are they found?
Malleus, incus, stapes
Middle ear - Found in the petrous portion of the temporal bone
Key features of the the ossicle structures and how they interact.
Malleus - head and handle - head has the incus articulation, handle attaches to tympanic membrane
Incus - Body and long limb - Body has the malleus articulation
Stapes - Base articulates with oval window, head articulates with long limb of incus
state and descrive the type of joint found between the auditory ossicles
Synovial joints:
Outer fibrous articular capsule surrounds the joint
Synovial membrane lines articular capsule
Synovial fluid-filled cavity lies within the joint
Articular (hyaline) cartilage lines articular surfaces
What is Conductive Hearing Loss
When there is a problem conducting sound waves anywhere along the route through the outerear, tympanic membrane or middleearauditory ossicles
State 4 examples of conductive hearing loss
Autoimmune conditions (i.e. rheumatoid arthritis) leading to inflammation of synovial membrane -> joint stiffness and eventually damage
Head trauma can lead to joint dislocation
Repeated acute otitis media -> joint scarring and stiffness
Otitis media with effusion -> mild conductive hearing loss
What are the portions of the external ear
Outer portion: auricle (pinna)
Inner portion: external acoustic meatus (or external auditory canal)
What kind of epithelium in the external ear?
keratinised stratified squamous epithelium
What is the Sensory Innervation to the Pinna:
Cranial nerves
Trigeminal nerve, mandibular division (CN V3) - Anteriorly
Facial nerve (CN VII) - Around concha
Vagus nerve (CN X) - Whole ear
Spinal nerves
Lesser occipital nerve (C2) - Posterior
Greater auricular nerve (C2, C3) - Inferior
How could pain in the external ear be caused by osteoarthritis (degenerative processes) in the neck region
Pain in the external ear may result from compression of one or more of the spinal nerves that supply the ear, as a result of osteoarthritis (degenerative processes) in the neck region
Anatomy, Histology & Nerve Supply of the External Acoustic Meatus
Anatomy:
S- shaped
Histology:
thin, adherent to cartilage and bone
contains ceruminous glands
Nerve Supply:
Cranial nerves V, VII & X
Key observable features of the tympanic membrane
Handle of malleus, Cone of light, Membrane, Incus
What should a healthy tympanic membrane look like?
The healthy tympanic membrane is a pale, grey, ovoid semi-transparent membrane situated obliquely at the end of the bony external auditory canal
The handle of the malleus is seen extending downwards and backwards, ending at the apex of the triangular “cone of reflected light”
The long process of the incus may be seen too
What is the function of the Pharyngotympanic Tube
Connects the middle ear with the nasopharynx.
Equalizes pressure on both sides of the tympanic membrane.
During swallowing the salpingopharyngeus muscle (one of the longitudinal pharyngeal muscles) opens the pharyngeal orifice of the pharyngotympanic tube
CN X (vagus) nerve supply
Allows mucociliary clearance and drainage of the middle ear
Dampens loud sounds (as it is closed at rest – most of it is cartilaginous)
How do infections in the nasopharynx move into the ear?
The mucosa of the pharyngotympanic tube is continuous with the nasopharyngeal mucosae infections from the nasopharynx can track up to the middle ear.
What is acute otitis media?
infection involving the middle ear space and is a common complication of viral respiratory illnesses
Viruses can infect the nasal passages, pharyngotympanic tube, and middle ear, causing inflammation and impairing the mucociliary action and ventilatory function of the pharyngotympanic tube to clear nasopharyngeal flora that enter the middle ear.
A middle ear effusion develops, and nasopharyngeal bacteria contaminate the effusion resulting in a purulent effusion
What is otitis media with effusion? And potential causes of persistent OME.
non-purulent effusion within the middle ear without signs of acute inflammation (also known as ‘glue ear’)
Persistence of OME may occur because of one or more of the following:
Impaired pharyngotympanic/eustachian tube function causing poor aeration of the middle ear
Low-grade viral or bacterial infection
Persistent local inflammatory reaction
Adenoidal infection or hypertrophy
Why are children more susceptible to ear infections?
In children, the pharyngotympanic tube is more horizontal and slightly narrower than in adults - this predisposes them to middle ear infections and the clearance mechanism is not as efficient
What is Sensorineural Hearing Loss
injury or pathology affecting the inner ear structures
Muscles of the middle ear
Tensor tympani muscle – attaches to the malleus and tenses the tympanic membrane when we hear loud noises.
Nerve supply: mandibular (V3) division of the trigeminal nerve (CN V)
Stapedius muscle – attaches to the stapes. It contracts during loud noises and prevents excessive oscillation of the stapes
Nerve supply: facial nerve (CN VII)
Both for acoustic reflex
What is hyperacusis
The experience of inordinate loudness of sound that most people tolerate well, associated with a component of distress. This experience has a physiologic basis - but it also has a psychological component.
Middle ear innervation
Tympanic plexus of nerves:
From glossopharyngeal nerve (CN IX)
Innervates mucous membrane of the middle ear
Sympathetic fibres from the sympathetic chain in the cervical region join this plexus
The plexus sits on the promontory which is formed by the cochlea in the inner ear
Chorda tympani - Facial nerve (CN VII)
Innervates the salivary glands.
Carries taste sensory fibres from the anterior 2/3 of the tongue back to the brain.
Types of upper respiratory viruses
Rhinoviruses (>100 serotypes)
Parainfluenza viruses 1-4
Coronaviruses
RSV
Adenoviruses
Enteroviruses (coxsackie, echo)
What causes Pharyngitis/Tonsillitis
Viruses (adenoviruses)
Bacteria – Strep pyogenes
What is Infectious mononucleosis?
Glandular fever
Constellation of symptoms and signs, not an aetiological diagnosis
Pharyngitis, lymphadenopathy (cervical, generalised), fever, malaise
Atypical mononuclear cells in peripheral blood
Epstein-Barr virus, cytomegalovirus, toxoplasmosis, HIV seroconversion
Lower respiratory tract viruses
Influenza viruses
Respiratory syncytial virus
SARS-CoV-2
Rare:
Varicella zoster virus (adults)
Measles virus (giant cell pneumonia)
Cytomegalovirus (immunocompromised)
SARS and MERS coronaviruses
How are influenzas typed?
TYPES – A, B, or C
On basis of internal proteins NP, matrix
SUBTYPES – A only
On basis of surface proteins, HA, NA
16 HA, 9NA known
Pathogenesis of influenza
Pneumotropic and lytic ie strips off respiratory epithelium
Removes 2 innate defence mechanisms – mucous secreting cells and cilia
Interferon production – circulates in blood (virus doesn’t)
What are potential complications of influenza
Pneumonia
myocarditis
Encephalitis
What is antigenic shift?
Occurs only in influenza A viruses
Genetic reassortment between human and non-human viruses leading to new subtypes
Describe respiratory Syncytial virus epidemiology
Enveloped paramyxovirus
–ve ssRNA encodes 9 polypeptides incl 2 surface proteins F,G
Causes LRTI in infants – bronchiolitis, pneumonia
High hospitalisation rates
Low mortality
Extremely common - global infection by age 2
How many recurrent episodes of upper respiratory tract infections are common in children
Six to eight per year
Risk factors of otitis media with effusion
Exposure to cigarette smoke
Bottle feeding
Older siblings or contact with older children such as in day care
Atopic rhinitis
Cleft palate
Down’s syndrome
Cystic fibrosis
Glue ear
Signs
hearing difficulty (for example, mishearing when not looking at speaker, difficulty in a group, asking for things to be repeated)
poor educational and language progress
When is surgical intervention necessary for otitis media with effusion
Persistent bilateral glue ear documented over 3 months with hearing loss in the better ear of 25-30 dBHL
What is a treatment for otits media with effusion?
A temporary grommet (a tympanostomy tube) is placed in the tympanic membrane.
This ventilates the middle ear, maintains normal middle ear pressures and reduces the risk of fluid building up in the middle ear.
Routine hearing tests for children in the UK
Newborn hearing screening
9months to 2.5 years of age – routine enquires about parental concerns with hearing tests arranged if necessary
4 to 5 years of age – preschool hearing test
typical speech and language development milestones
By 6 months: Turn towards a sound when they hear it
1 year: Listen carefully, and turn to someone talking on the other side of the room.
Babble strings of sounds, like ‘no-no’ and ‘go-go
18 months : Start to understand a few simple words, like ‘drink’, ‘shoe’ and ‘car’. Also simple instructions
2 years: Understand between 200 and 500 words and simple questions and instructions. E.g. ‘where is your shoe?’ and ‘show me your nose’.
3 years: Listen to and remember simple stories with pictures.
Understand longer instructions, such as ‘make teddy jump’ or ‘where’s mummy’s coat?’
Understand simple ‘who’, ‘what’ and ‘where’ questions
Describe the larynx epithelia
Lined by pseudostratified columnar ciliated epithelium, except epiglottis & vocal cords – Stratified Squamous Non Keratinising
Trachea histology
Interior to exterior:
PSCC
Connective tissue
Seromucous acinar glands
Perichondrium
Hyaline cartilage
Horse-shoe shaped rings of cartilage – ends connected posteriorly by the trachealis muscle (smooth)
Bronchi structure
Seromucous glands
Cartilage: complete rings (extrapulmonary)
Cartilage: incomplete rings (intrapulmonary)
Spirally arranged smooth muscle
Bronchioles structure
1mm in diameter
Simple columnar/cuboidal epithelium
NO glands
NO cartilage
Prominent smooth muscle
Gradual decrease in goblet cells & cilia
Alveoli structure
Thin walls lined by simple squamous epithelium
Type I pneumocytes (gas exchange)
Type II pneumocytes (surfactant production) - reduces surface tension, preventing collapse
Capillaries in mid-wall
Elastic and reticular fibres
Alveolar macrophages (no cilia or mucus for defence
Lung (pulmonary) interstitium
Basement membrane and surrounding interstitium, which separates the endothelial cells from the alveolar lining epithelial cells.
Interstitial space (pulmonary interstitium) contains fine elastic fibers, small bundles of collagen plus some fibroblast-like interstitial cells, smooth muscle cells, mast cells, and rare lymphocytes or monocytes.
Describe the alveolar air blood barrier
Endothelium - Fused basement membrane - epithelium
Describe the pleura
2 layers of opposing mesothelium
Visceral pleura
Parietal pleura
Pleural “cavity” in-between
What is the conducting aspect of the respiratory tract?
Trachea > Primary bronchi > Lobar (secondary) bronchi > Segmental (tertiary) bronchi
What is the respiratory aspect of the RT?
Branching of terminal bronchioles to respiratory bronchioles and alveolar sacs
Features of the trachea. Vertebral levels, features, innervation
Trachea starts at cricoid cartilage (C6) is palpable superior to suprasternal notch
Trachea bifurcates at T4 (sternal angle) into right and left main bronchi. Main bronchi enter lung hilum at T5/6 vertebral level
Incomplete ring of hyaline cartilage
Trachealis muscle
Left main bronchus passes under arch of the aorta and is longer and narrower than right. Right is more vertical
Tracheobronchial innervation = vagus nerve (CNX), sympathetic nerves
What is relevant about the bronchial tree surgically?
Each segment is functionally independent - can be surgically resected
Right lung lobes and segments
Superior lobe
Apical segment (1)
Posterior segment (2)
Anterior segment (3)
Middle lobe
Lateral segment (4)
Medial segment (5)
Inferior lobe
Apical segment (6)
Medial basal segment (7)
Anterior basal segment (8)
Lateral basal segment (9)
Posterior basal segment (10)
What segments of the lung are usually affected in supine patients?
Apical basal and posterior basal dependent
Fluid / secretions can collect– postural drainage)
Left lung lobes and segments
Left lung has 9 segments
No middle lobe – lingula instead
Apical and posterior segments of superior lobe may be combined
Inferior lobe – medial basal segment is smaller, shares bronchus with anterior basal segment
What are the fissures of the lungs?
Oblique on both
Horizontal on the right
What is the Hilum? and what is its structure?
Hilum of the lung – connects lung to mediastinal structures
Pulmonary artery
Bronchi
Pulmonary veins
Mediastinal relations of the left lung
Aortic Arch
Cardiac impression
Subclavian artery
Brachiocephalic vein
Stomach (diaphragm)
Mediastinal relations of the right lung
Vena cava S and I
Oesophagus
Azygos vein
Brachiocephalic vein
Liver (diaphragm)
What is the innervation of the diaphragm?
Phrenic nerve - C3,4,5
Major structures passing through the diaphragm (+vertebral levels)
Inferior vena cava (T8 vertebral level)
Oesophagus (T10)
Aorta (T12)
Layers of the intercostal muscles (out to in) and their function
Externals = inspiration
Internals + innermost = expiration
Describe the Neurovascular bundle in costal groove of superior rib
Intercostal vein
artery
nerve
Found superiorly
Collateral branches found inferiorly
What is the External intercostal muscle action on the thoracic cage
Upper ribs = Increase anteroposterior diameter
Lower ribs = Increase transverse diameter
Describe the pleura
Visceral pleura: covers lung
Parietal pleura: covers internal surface of chest wall, mediastinum, diaphragm
Pleural “cavity” in-between
Lined with serous fluid
What is a pneumothorax
collapsed lung
What is the nerve supply of the parietal pleura?
Nerve supply of parietal pleura is the phrenic nerve (C3,4,5) for mediastinal and diaphragmatic pleura
Intercostal nerves for costal pleura
Describe how a collapsed lung could be resolved.
A chest drain is inserted in mid-axilliary line, 5th or 6th IC space, to remove air (point upwards) or fluid (point downwards).
Describe the complications of a tension pneumothorax
In a tension pneumothorax, air that continues to enter the pleural cavity can’t escape. The trachea deviates towards the contralateral side and can form a “valve” that prevents air entering the unaffected lung.
Where are the surface markings of the lung?
Oblique fissure T4 to 6th costal cartilage
Horizontal – follows 4th intercostal space from sternum to meet oblique fissure at 5th rib
Apex is 2 cm above medial 1/3 of clavicle
Cardiac notch of left lung below T4
Where is the Pleural surface exposed?
Exposed above clavicle
Pleura is at 12th rib or lower, exposed here at the renal angle
Describe biology behind a cough
From trachea to alveoli sensitive to irritants.
Afferents utilize primarily CN X (Thevagus nerve).
Process
2.5 L of air rapidly inspired
Epiglottis closes and vocal chords close tightly
muscles of expiration contract forcefully which causes pressure in lungs to rise to 100 mm Hg
Epiglottis and vocal chords open widely which results in explosive outpouring of air to clear larger airways at speeds of 75 – 100 MPH
Sneeze
Associated with nasal passages
Irritation sends signal over CN V (The trigeminal nerve) to the medulla:
Response similar to cough, but in addition uvula is depressed so large amounts of air pass rapidly through the nose to clear nasal passages
What can depress respiratory defence mechanisms
Chronic alcohol is associated with an increase incidence of bacterial infections.
Cigarette smoke and air pollutants is associated with an increase incidence of chronic bronchitis and emphysema.
Occupational irritants is associated with and increased incidence of hyperactive airways or interstitial pulmonary fibrosis
Common cold
Viral disease of the upper respiratory system.
Caused by a variety of viruses;
rhinoviruses and coronaviruses are the most common.
Symptoms are sneezing, runny nose, and congestion.
Viruses prefer a slightly cooler temperature hence the upper respiratory system.
Self-limiting, 7days or so
Sinusitis
Inflammation of the mucosal lining of paranasal sinuses.
Characterised by:
Facial pain
Nasal obstruction
Nasal discharge
Post-nasal drip from sinusitis is irritating to the larynx and may cause a persistent cough.
What bacteria most commonly cause sinusitis
Streptococcus pneumoniae
Haemophilus influenzae
Staphylococcus aureus
Streptococcus pyogenes (Group A) – less common
Otitis externa
Otitis externa
Aka Swimmer’s ear
Outer ear exposed to water lowering acidity
Microbes accumulate and colonise
Bacterial
Staph aureus
Enteric bacteria
Malignant OE in immunocompromised:
Pseudomonas – multi-drug resistant
Fugal
Aspergillus
Candida
Symptoms of malignant otitis media
persistent and foul-smelling yellow or green drainage from the ear
ear pain that gets worse when moving the head
hearing loss
persistent itching in the ear canal
fever
difficulty swallowing
weakness in the facial muscles
loss of voice, or laryngitis
swollen and red skin around the ear
Otitis media pathogens
Haemophilus influenzae
Strep pneumoniae
Moraxella catarrhalis – Gram neg cocci
Also anaerobes such as Prevotella
Pharyngitis, laryngitis, tonsillitis
Most commonly of viral causes
Bacterial – Strep Group A (Strep pyogenes)
Sore throat
Erythema of the pharynx
Often enlargement of the tonsils (Tonsillitis)
Scarlet fever
Caused by Strep pyogenes through inhalation, skin contact or oral route
Leading cause of death in children in the early 20th century
Most commonly affects children between 5 to 15 y.o.
Fever followed by rough red rash over trunk and abdomen then spreads to entire body
Accompanied by pyrexia, lymphadenopathy, aches and nausea
Diphtheria
Caused by Corynebacterium diphtheriae
Gram-positive, rod-shaped bacteria
Irregular, club-shaped or V-shaped arrangements
Toxin induces epithelial necrosis embedded in fibrin and white cell infiltrates forming pseudomembrane in trachea
Can be fatal - multisystem toxaemia and myocarditis
Tracheitis
Rarely occurring in adults, affects primarily infants and children
Symptoms:
Severe coughing
Nasal flaring
Breathing difficulties
Cyanosis
Viral or bacterial
Bacterial causes:
Most common Staph aureus including MRSA
Strep pyogenes
Strep pneumoniae
Haemophilus influenzae
Moraxella catarrhalis
Enteric bacteria
Bronchitis
Symptoms:
coughing up mucus
wheezing
shortness of breath
chest discomfort
Cough lasting few weeks
Primarily viral
Occasionally bacterial
Strep pneumoniae
Haemophilus influenzae Moraxella catarrhalis
Bronchiolitis
Viral causes (RSV – most common, Influenza, parainfluenza, Rhinovirus)
Affecting infants up to 2 y.o.
Preceded by viral URTIs
Cough, wheezing followed by respiratory distress
Pneumonia
Inflammation of the lung affecting primarily the alveoli but also the bronchioles and bronchi
Pathology includes build up of fluid in the form of mucus and / or blood in the alveoli
Symptoms: Productive or dry cough, chest pain, fever, and troubles during breathing
Streptococcus pneumoniae is the most commonly identified bacterial cause of CAP in all age groups worldwide.
Whooping cough - Pertussis
Caused by Gram negative coccobacilli Bordetella pertussis
Re-emergent as a serious respiratory illness affecting infants and children but also occasionally young adults
Toxin similar to cholera toxin
Explosive cough as disease develops into paroxysmal stage (series of consecutive bursts of cough with increasing intensity)
Rapid exhaustion
Cyanosis and Convulsion
Anatomical Dead Space
Morphological
Volume of conducting airways
Air flushed out with each new breath
~ 150ml
Determined by:
Anatomy/radial traction
Subject size and posture,
Size of breath (tidal volume)
Physiological Dead Space
anatomical dead space and alveoli not perfused/diseased
Describe Single breath method
Measures rate of gas transfer across the
Air-blood barrier
patient inhales test gas (with known v. small concentration of CO) and holds breath for 10 sec
Rate of CO disappearance from alveolar air is measured by comparing expired air with inspired air (infrared analyser)
25mL/min/mmHg
What is VQ mismatch
VQ mismatching is the most common cause for a fall in PaO2 in resp. disease
VQ mismatch increases the area that is not used for gas exchange.
PaO2 falls, the PA-PaO2 gradient increases
Breathing rate may increase
Range of pathologies :
Alveolar structural problems
Lack of inspired oxygen
Respiratory failure,
Lack of circulation/ blood flow
Causes of type I respiratory failure
Decreased PaO2
Hypoventilation; Low O2 in inspired air; V/Q mismatch
Decreased mixed venous O2 content
Increased metabolic rate (e.g. fever) ; Decreased cardiac output (cardiac failure); Decreased arterial O2 content (e.g. Diffusion problem?)
Anatomical intrapulmonary shunts
Congenital cardiac lesions (Fallor’s tetralogy) section of lung is unventilated and blood bypasses the lungs
altering bronchiolar and arteriolar radius in response to 02 and CO2 levels
Bronchioles dilate in response to raised PaCO2 (hypercapnia) to improve airflow.
Pulmonary arterioles constrict to low PaO2 (hypoxia) to reduce flow and redirect blood to better perfused areas
O2 carriage in blood
Physically dissolved (1.5%) - 0.3 ml O2/dL blood
Bound to haemoglobin in RBC (98.5%) - each gm of Hb carries 1.34 ml O2 ([Hb] = 15gm /dL)
O2 pressure
(PaO2)
Amount of oxygen dissolved in plasma
= 0.3 ml O2/dL
O2 capacity
Amount of O2 bound to Hb
O2 content
(CaO2)
Amount of O2 bound to Hb + dissolved O2
O2 saturation
The % of available binding sites bound
to O2 . This stays constant with the PaO2.
Methaemoglobin and methhaemoglobinemia
1% of haemoglobin exists in oxidised state (Fe3+) methaemoglobin (Met Hb)
Limited by Methaemoglobin reductase in RBC
Excess Met Hb
Congenital (autosomal recessive, HbM)
Acquired (e.g. nitrates/nitrites)
Blue-ish/brown blood
Factors that reduce Hb-O2 affinity & help O2 unloading to tissues
Acidic pH (Bohr effect)
Increased PaCO2
Raised body temperature
2,3, biphosphoglycerate (2,3 BPG)
Factors that increase Hb-O2 affinity & prevent O2 unloading to tissues
Alkaline pH
Reduced PaCO2
Lowered body temperature
Fetal haemoglobin
Myoglobin
Myoglobin (Mb) shuttles O2 from the cell membrane to the mitochondria
No co-operative binding
Higher affinity for O2 than haemoglobin
Cardiac muscle
Even at low PO2
Allows Mb to store O2
CO2 carriage in blood
In solution in plasma (9% )
Carbamino haemoglobin (13%)
Bicarbonate ion (78%)
Describe how RBC’s react to CO2
Carbonic anhydrase converts CO2 to HCO3-
Diffuses into plasma swapping with Cl-
Oxyhaemoglobin dissociates to release O2 & free Hb so
H+ is buffered in HHb
haemoglobinopathy examples - 5
Mutations can cause methemoglobinemia (HbM) - replacement of histidine makes the heme group inaccessible to methaemoglobin reductase
Spontaneous denaturation of hemoglobin - causes hemolytic anaemias, Insoluble protein aggregates (Heinz bodies)
Mutations can affect oxygen-binding affinity - e.g increased affinity makes it difficult to unload oxygen – polycythaemia and cyanosis
Mutations alter processing or degradation of mRNA or proteolytic degradation of α – or β- chains - Thalassemias
Haemoglobins with reduced water solubility cause sickling disorders - Sickle cell disease is a mutation in which a glutamate residue of the β chain is replaced by valine. This gives abnormal haemoglobin S (HbS) which has decreased water solubility (particularly the deoxy form)
Acidosis
a blood pH below 7.35.
Depresses the CNS through depression of synaptic transmission (coma).
Alkalosis
a blood pH above 7.45.
Overexcitability of the PNS then CNS through facilitation of synaptic transmission (spasms, convulsion & death)
Lines of defence against pH disorders
- Chemical buffers
intracellular and extracellular fractions of a sec - Adjusting ventilation to change PaCO2
restores 50-75% to the way to normal pH
mins - Adjusting renal acid or alkalis excretion
Long term regulation
hrs to days
The Carbonic Acid - Bicarbonate Buffer System
Quantitatively the most important ECF buffer though not the strongest.
Carbonic anhydrase CO2 + H2O H2CO3 ↔ H+ + HCO3-
CO2 is regulated by the lungs
Chemoreceptors
secs
HCO3- & H+ are regulated by the kidneys
H+ excreted
HCO3- reabsorbed or excreted
hours/days
Simplified Henderson-Hasselbach Equation
pH ∝ [HCO3- ] (controlled by the kidneys)/ PCO2 (controlled by the lungs)
BGA motion kf thoughts
Is the pH is normal, high (alkalosis) or low (acidosis)
Is PaCO2 or HCO3- out of their normal range ?
Which of these abnormal results corresponds with acid-base state?
E.g. if the pH is high (alkalosis) this could be due to either a low PCO2 or high HCO3-– which one is seen in the data?
If the PaCO2 level corresponds with the pH, this is a respiratory cause. If the HCO3- is the culprit, it is a non-respiratory cause.
- Look at the other if it is in the normal range, it is not yet compensating for the problem (i.e. an acute case). If it is not in the normal range it is trying to correct the pH change…..
Define Respiratory failure
inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels.
Type 1 respiratory failure
Failure of oxygenation
Hypoxaemia with low or normal CO2
PaO2 < 8 Kpa (<60 mmHg)
i.e. lung failure - usually due to damage to the lung parenchyma, airways or pulmonary vessels. (Eg. Emphysema, ILD, Pneumonia)
Type 2 respiratory failure
Failure of ventilation (hypoxaemia and hypercapnia)
PaO2 < 8 Kpa
PaCO2 > 6 Kpa (>50 mmHg)
i.e. pump failure - failure of respiratory muscles, CNS respiratory drive or nerves connecting the two.
Common causes of T1 Respiratory failure
Acute asthma
Pneumonia
Pulmonary oedema
Pulmonary embolism
Pneumothorax
Common causes of T2 Respiratory failure
COPD
Obesity Hypoventilation Syndrome
Kyphoscoliosis
Neuromuscular weakness (e.g. MND)
Drugs e.g. opiates
ABCDE approach of RF
A - ensure airway patent and protected
fast bleep anaesthetist if airway at risk
B - sit up and give high flow oxygen
C - secure iv access
may need urgent fluid
D - if comatose, think of drug-induced respiratory depression
E- Get senior help
Investigations for respiratory failure:
Bedside tests
Bloods
Basic imaging
Specialist imaging
Physiological tests
Bedside tests
Basic observations – saturations, respiratory rate, BMI
Sputum sample
Urinary antigens for pneumonia
Bloods
FBC, U+E’s, LFT, CRP
Arterial blood gas
Basic imaging
Chest x-ray
Specialist imaging
CT chest
Thoracic ultrasound
Physiological tests
Spirometry
Respiratory muscle strength testing
Overnight oximetry
Pneumonia
Inflammatory reaction of the alveoli and interstitium of the lung usually caused by an infectious agent
Characterised by
Inflammatory exudate in the alveolar space that consolidates
Inflammation of alveolar septa
Pneumonia stages
Neutrophils and fluid in alveoli, congested capillaries
(RED HEPATIZATION)
Organisation: exudates transformed to masses: macrophages and fibroblasts.
Symptoms and treatment of acute bacterial pneumonia
Fever, chills, dyspnoea
Cough with or without sputum (purulent – bacterial, watery – viral)
Crackles on auscultation
Consolidation in radiograph
Diagnosis:
Sputum: Bacteria/virus. Gram staining, bacterial culture (suitable antibiotic)
X-ray
FBC
Treatment: Antibiotic (empirically-can be changed on results)
Causative organism of pneumonia
Bacteria
Gram +ve: S pneumoniae, Staphylococcus aureus
Gram –ve: Haemophilus influenzae , Klebsiella pneumoniae, Legionella pneumophila
Viruses
Mycoplasma: Mycobacterium tuberculosis
Fungi: Pneumocystis jiroveci
Inorganic agents (inhaled dusts or gases)
Effect of alcohol and smoking on pneumonia risk
Alcohol: impairs cough reflex, increased aspiration
Cigarette smoke: reduced mucociliary and macrophage action
Antomical types of pneumonia
Lobar pneumonia: alveoli-alveoli
Organisms access alveoli and rapidly spread via alveolar pores (connect adjacent alveoli)
Adult poor hygiene/malnourished/alcoholic
Bronchopneumonia: Bronchi to alveoli
Organisms colonise bronchi and spread to alveoli
Affected areas consolidated locally –lobules and eventually whole lobes-confluent
Young/elderly/immobile
Immuno compromised patients - peneimonina
Opportunistic infection (organisms that rarely cause disease in normal host)
Bacteria: pyogenic
Viruses: Cytomegalovirus (CMV)
Fungi: Pneumocystis jiroveci
Aspiration pneumonia
Often necrotising, abscess formation in survivors, frequent cause of death
Anaerobic bacteria: oral flora
Aerobic:
S pneumoniae, S aureus, H influenza, Pseudomonas aeruginosa
6 possible outcomes of pneumonia
Resolution: destruction of connective tissue/vasculature minimal/absent. Neutrophils destroy organism, exudate liquified by neutrophil enzymes (fibrin breakdown /phagocytosis of dead cells), this is coughed up/reabsorbed by capillaries/drained in lymph. Epithelial stem cell proliferation and differentiation into type I and II pneumocytes
Organization: scar tissue/fibrosis from destruction of connective tissue. Possible bronchiectasis.
Abscess formation
Empyema
Bacteremia (meningitis/arthritis/infective endocarditis)
Death
What is Obstructive lung disease?
Limitation of airflow due to obstruction causes increased airway resistance
Airway narrowing (asthma), loss of elasticity (emphysema) or increased secretions (bronchitis/asthma)
What is restrictive disease
Restrict normal lung movement during respiration
Reduced expansion of lung parenchyma
Decreased total lung capacity
What is COPD?
Chronic bronchitis and emphysema often co-exist and are called chronic obstructive pulmonary disease (COPD).
Chronic Bronchitis - diagnosis, symptoms, risk factors
Defined clinically rather than morphologically (persistent productive cough for at least 3 consecutive months in at least 2 consecutive years)
Mucus hyper-secretion in large airways (trachea and bronchi) or small airways (bronchiolitis)
Cigarette smoking (most important cause), also common in urban areas
Chronic Bronchitis - Pathophys
3Hs:
Hypertrophy and hyperplasia of mucous glands
Hypersecretion of mucus - increase in goblet cells in the epithelium
Inflammation – T cells, neutrophils and macrophages (no eosinophils – in contrast to asthma)
Chronic bronchiolitis
Small airway disease:
Goblet cell metaplasia
Mucus plugs bronchiolar lumen
Inflammation
Bronchiolar wall fibrosis
Luminal narrowing and airway obstruction
Emphysema
Permanent dilation of respiratory bronchioles and alveoli
Destruction of elastic wall tissue – without significant fibrosis
Loss of elasticity causes difficulty in expiration and loss of surface area as air sacs coalesce
Types of emphysema
Centriacinar (CA) or centrilobular:
Dilated respiratory bronchioles
Most common (x20)
More common in upper lobes
Smoking related
Panacinar (PA) Panlobular:
Dilated alveoli
More common in lower lobes
Hereditary (presents earlier)
presentation of emphysema without bronchitis
Without bronchitis
Dyspnoea, prolonged expiration, barrel chest
Prolonged onset >40 years
Pursed lips
‘Pink puffer’ – dyspnoea & adequate oxygenation of haemoglobin
presentation of emphysema with bronchitis
With bronchitis
Dyspnoea less prominent
Patient retains CO2 – hypoxic and cyanotic
‘Blue bloater’ – cyanotic and tend to be obese
Pathogenesis of emphysema
Normally, anti-protease enzymes, such as α1 anti-trypsin, and anti-oxidants balance enzymes that digest proteins (e.g. elastase), cytokines and oxidants
Cigarette smoke contains abundant reactive oxygen species which cause tissue damage and inactivates anti-proteases.
Inherited Deficiency in α1 anti-trypsin (presents earlier)
Environmental toxins stimulate inflammation -
Neutrophils, macrophages and lymphocytes accumulate - Epithelial injury and ECM proteolysis due to presence of elastases, cytokines and oxidants
Bronchiectasis
Permanent dilation of main bronchi and bronchioles from pulmonary inflammation and scarring due to infection, bronchial obstruction or lung fibrosis.
Airways then dilate, as surrounding scar tissue (fibrosis) contracts
Secondary inflammatory changes, lead to further destruction of airways.
Symptoms are a chronic cough with dyspnoea and production of copious amounts of foul-smelling sputum
Damage to epithelium causes bleeding (haemoptysis)
Clubbing of fingers
Morphology of bronchiectasis
Primarily affects the lower lobes: on both sides. Vertical air passages
Up to 4x expanded
Acute and chronic inflammatory exudate
Epithelial ulceration
Fibrosis of bronchial and bronchiolar walls, peribronchial fibrosis
Causes of bronchiectasis
Obstruction: tumours/foreign bodies/impaction of mucus. Localised to that lung segment. As a complication of asthma/chronic bronchitis
Infection: Necrotising pneumonia esp. with virulent organisms. TB. Mixed flora on culture
Congenital/hereditary:
Cystic fibrosis: Production of abnormally viscoid mucus causes obstruction and predisposes to infection
Immunodeficiency: immunoglobulin deficiencies –predispose to infection
Kartagener syndrome (immotile cilia syndrome) –impaired mucociliary clearance-stagnation of secretions
Bronchiectasis is predisposed by two things
Interference with drainage of bronchial secretions
Recurrent and persistent infection weakening bronchial walls
Acute respiratory distress syndrome-ARDS
Caused by diffuse alveolar damage as a consequence of direct (pneumonia/aspiration of gastric contents) or indirect (sepsis/severe trauma) lung injury.
Acute inflammation of alveoli, heavily involving neutrophils, rapidly damages capillaries and epithelium as a result of diffuse alveolar damage
uncontrolled inflammation
Acute onset of dyspnoea and hypoxaemia due to vascular leakiness and loss of surfactant affecting gaseous exchange and expansion of alveoli
High mortality rate (60%)
Pathophysiology of ARDS
Damage > interstitial edema (60% death) > Type II pneumocyte regeneration and inflammation of interstitium > organisation leading to interstitial fibrosis > 10% survive: 20% joneycomb lung and die
Idiopathic Pulmonary Fibrosis
Chronic Persistent alveolitis: inflammation of alveolar walls and spaces
Stimulated fibroblasts deposit collagen and ECM excessively for an extended time - Patchy interstitial fibrosis that worsens with time
Fibroblastic foci – become more collagenous and less cellular
Causes collapse of alveolar walls and formation of cystic spaces – honeycomb fibrosis/ honeycomb lung
Pneumoconioses examples
Asbestos (asbestosis), silica (silicosis), coal dust (coal workers pneumoconiosis)
What size particles cause damage when inspired
< 0.5 μm: OK.
1-5 μm particles reach distal airways and are phagocytosed by macrophages. If reactive (e.g. crystalline silica) macrophages are stimulated to mediate inflammatory response and fibroblast proliferation.
5-10 μm particles don’t reach distal airways
Astma
Asthma is a chronic inflammation of the airways which results in hyper-responsive airways with episodic, reversible airway narrowing.
Intermittent and reversible airway obstruction
Chronic bronchial inflammation with eosinophils
Bronchial smooth muscle hypertrophy and hyper-reactivity
Asthma presentation
cough
wheezing
shortness of breath
sputum production
nocturnal cough or wheezing
Types of asthma
Atopic/extrisic: 70%. Caused by exposure to environmental allergens (house dust/pollen/animal/ food).
Non-atopic/intrinsic: no obvious external allergen trigger. Cold exposure/exertion/viral inflammation reduces threshold to irritants. Treatment similar to atopic
Early and late asthma
Early reaction:
Bronchoconstriction
Hypersecretion of mucus leading to plugging of airways
Late reaction:
Inflammation – activation of leucocytes
Mucosal oedema and muscle hypertrophy – narrow the lumen
Epithelial cells produce chemokines to attract more TH2 cells and eosinophils
Repeated inflammation leads to airway remodelling
Asthma morphological changes
Excess mucus production by goblet cell and glandular hypertrophy
Bronchial wall oedema due to inflammatory exudate: eosinophil and mast cell accumulation
Smooth muscle hypertrophy and fibrosis
Which type of hypersensitivity are allergies?
Type I
Describe a type I hypersensitivity reaction
Allergen is taken up and presented by APCs.
B cells produce IgE antibodies; which attach to mas cell Fc receptors
Allergen then binds to the mast cells.
Rapid IgE engagement and receptor cross-linking as a trigger.
Rapid degranulation and histamine release = allergic response.
Urticaria
raised redness and irritation termed urticaria (from Urtica, the Latin name for stinging nettles), or more commonly called hives.
Angioedema
Activation of mast cells in deeper subcutaneous tissue can result in a more diffuse swelling termed an angioedema.
Can arise from passage of allergen systemically.
Anaphylactic shock
Extreme cases of type I
Loss of consciousness, hives, swelling of tongue and throat tissues
Requires rapid treatment with epinephrine (adrenaline) to stimulate smooth muscle relaxation, facilitating blood flow and a restoration of blood pressure.
Describe the balance of Th1 and Th2 cells
Th1 produce IFNy which inhibits Th2.
Th2 produce IL10 which inhibits Th1.
1 activate macrophages
2 activate mast, B and eosinophils
Allergy treatment
Anti-histamines available over the counter, block histamine binding to its receptor on vascular endothelium to reduce an inflammatory response.
Application of hydrocortisone cream to suppress/reduce an inflammatory response.
Maintenance of a food diary and specific food avoidance.
Type II hypersensitivity
Binding of small molecules (including drugs) to cell surfaces, producing modified structures that are recognised as foreign by the immune system.
IgG or IgM Abs are directed against cell surface and ECM antigens.
The immune response damages cells and tissues by activating complement and/or by recruiting effector cells such as neutrophils for phagocytosis.
Type III hypersensitivity reactions
Soluble immune complexes of antigen and IgG antibody that do not become cleared by complement binding and phagocytosis mechanisms.
They are then deposited at the walls of small blood vessels triggering a localised immune reaction, complement binding and phagocytosis.
Type IV hypersensitivity reactions
Arise from triggering antigen-specific effector T-cells, rather than the direct engagement with antibodies.
Requires antigen processing and presentation so takes 1-3 days before symptoms become evident, hence also termed delayed-type hypersensitivity.
Dorsal Respiratory Group (DRG)
Extends the length of the medulla
Neurones are located in the nucleus tractus solitarius (NTS) which is the sensory terminal or the vagus and glossopharyngeal nerves that transmits sensory signals from many different receptors to the respiratory centre
Repetitive ‘ramped’ bursts of inspiratory neuronal action potentials for 2 secs on (allowing inspiration) then 3 sec off (allowing expiration)
Allows steady increase in lung volume rather than inspiratory gasps.
The output is to the inspiratory muscles
Ventral Respiratory Group (VRG)
Either side of the medulla and anterior and lateral to the DRG
Located in the nucleus ambiguus and nucleus retroambiguus
Differ from the DRG:
Some neurones in the VRG cause inspiration and some cause expiration
No role in the basic rhythmical oscillations
Inactive in normal, quiet breathing as the DRG is active and the expiration is passive
Involved in active breathing e.g. greater than normal ventilation, and contributes to extra respiratory drive e.g. activity increases with exercise, dyspnoea, lung disease
Basic respiratory rhythm is modified by….
Cerebral cortex - Voluntarily change breathing patterns
Hypothalamus & limbic system – emotional changes
Baroreceptors, Thermoreceptors, mechanoreceptors
e.g. stretch receptors in the walls of the bronchi and bronchioles activate the ‘ inspiratory – off’ switch to stop inspiration when tidal volume increases to approx. 1.5 L (Hering-Breuer inflation reflex)
Chemoreceptors – chemical control
Pneumotaxic centre
Feeds into DRG
Limits inspiration
Controls rate and depth of breathing
The stronger the signal, the shorter the inspiration and faster rate
Apneustic center
Modulates breathing cycle (e.g. no abrupt halt in inspiration).
Where are peripheral chemoreceptors found?
Carotid bodies - exert the predominant, immediate effect on ventilation
5 x as fast as central chemoreceptors
Good for rapid responses e.g. exercise
Aortic bodies - have more effect on the cardiovascular system
Describe peripheral chemoreceptors in the carotid bodies
Bilateral carotid bodies found in the bifurcation of the common carotid arteries alter their nerve firing rate.
Afferent glossopharyngeal nerve transmits to the DRG
Carotid body special features: Small nodules always exposed to arterial blood, receiving a very high blood flow
Type I, glomus cells, are the chemosensitive cells of the carotid bodies – O2 sensitive K+ channels cause depolarisation and neurotransmitter release
Peripheral chemoreceptor sensitivity
Primarily respond to decreased PaO2 - elicit the ventilatory response to hypoxia
Drop in PO2 must be dramatic so do not play role in everyday regulation of ventilation
Sensitive to changes in arterial pH
Increased H+ (acidosis) > decreased H+ (alkalosis)
Sensitive to changes in PaCO2
Elicit initial 20% response to PaCO2 (hypercapnia) only
Central chemoreceptors
Chemosensitive area located bilaterally 0.2 mm beneath the ventral surface of the medulla oblongata - Ventrolateral medulla & the medullary naphe
Insensitive to PaO2
Very sensitive to PaCO2 changes manifested as CSF pH changes
Elicit 80% of the ventilatory change to PaCO2
after the initial peripherally mediated effect
Why could giving oxygen induce a coma
Chronic hypercapnia causes chemoreceptor adaptation & depresses ventilation:
Increased PaCO2 gives resp. acidosis - This lowers the CSF pH, but bicarbonate compensation returns the CSF pH back to normal
The central chemoreceptors are less sensitive to further changes in PaCO2 so minute ventilation depends on the hypoxic drive via the carotid bodies
If pure O2 given – this depresses carotid response reduces hypoxic ventilation drive
What neurotransmitter is released and what receptors are involved at the ganglia and on the target organ in the parasympathetic nervous system?
ACh at nicotinic ACh receptors at the ganglia
ACh at muscarinic ACh receptors on the target
What neurotransmitter is released and what receptors are involved at the ganglia and on the target organ in the sympathetic nervous system?
ACh at nicotinic ACh receptors at the ganglia
Noraadrenaline at adrenergic receptors on the target (ACh at adrenal medulla and sweat glands)
Muscarinic ACh intracellular signalling
ACh binds > Gq activated > PLC activated > Converts PIP2 to IP3 and DAG > IP3 binds IP3 receptor on sarcoplasmic reticulum > Ca2+ release > Contraction via MLCK
Parasympathetic activation causes
Salivation, decreased HR, Bronchoconstriction, Secretion, Increased GI motility, Contraction of detrusor muscle, relaxation of sphincter: micturition
Drugs acting at muscarinic receptors
Agonists: ACh, Muscarine, Pilocarpine
Antagonists: Atropine, Ipratropium, Tiotropium
Atropine, Ipratropium, Tiotropium characteristics for administration
Atropine: Crosses membranes easily
Ipratropium: Fast-acting, Short duration, Charged - don’t cross membranes easily
Tiotropium: Slow acting, Long duration, Charged - don’t cross membranes easily
Actions of atropine
Low dose
Dry mouth
Increases heart rate
Dilation of pupils, blurring of near vision
Reduced peristalsis
Difficulty in micturition
High dose
Acetylcholinesterase
enzyme that breaks down acetylcholine into acetate and choline. The choline is taken up into the presynaptic terminal.
Acetylcholinesterase inhibitors and “antidotes”
neostigmine (used for myasthenia gravis) and poisons (e.g. novichok, Sarin gas, head lice treatments).
Pralidoxime is a drug which can reverse the binding but only if given soon after the irreversible inhibitors.
Relative potency at α-adrenergic receptors
adrenaline > noradrenaline > isoprenaline
Relative potency at B-adrenergic receptors
isoprenaline > adrenaline > noradrenaline
β1-adrenergic receptors
adrenaline = noradrenaline
β2-adrenergic receptors
adrenaline > noradrenaline
What Sympathetic receptors are predominantly found at the:
Heart
Lungs
Gut
Vessels
Heart - B1
Lungs - B2
Gut - A1 and B1
Vessels - A1 (constriction) and B2 (dilation)
Adrenergic control in the heart
β1 receptors are coupled to Gs G protein and increase heart rate and force of contraction of cardiac muscle.
Gs G proteins signal via cAMP but the signalling for changing the heart rate and force of contraction are slightly different…
How do Gs proteins signal
Gs G proteins signal via cAMP
Heart rate is controlled by cAMP activating Na+ ion channels.
Force of contraction is controlled by cAMP induced PKA activating Ca2+ ion channels
How does Adrenaline cause bronchodilation
Adrenalin > B2 receptor > cAMP up > PKA activated > Phosphorylation of MLCK > relaxation
What type of drug could be used for bronchodilation and how is it better than adrenaline
β2 agonist e.g. salbutamol
More resistant to metabolism by monoamine oxidase
More resistant to metabolism by Catechol-O-methyltransferase
Salbutamol vs salmeterol
Salmeterol is longer lasting - 12 hours
Salbutamol 4-6h
Drug interfering with NA reuptake
cocaine and amphetamine are both noradrenaline transporter inhibitors
β2-adrenergic agonists – adverse effects
Tachycardia and arrhythmias
Paradoxical bronchospasm (rare)
Hypokalaemia
Skeletal muscle tremor (most common)
Hypoxaemia
Muscarinic receptor antagonists adverse effects
Dry mouth
Blurred vision
Paradoxical bronchoconstriction
Urinary retention
Methylxanthines: adverse effects
CNS stimulation
Gastrointestinal disturbances
Cardiovascular effects
Hypokalaemia
Omalizumab
an anti-IgE antibody
Corticosteroids adverse reactions
With prolonged high doses:
Adrenal suppression
Osteoporosis
Metabolic effects
Cushing’s syndrome
Suppression of response to infection
GI upset
Hypertension
How can Oropharyngeal candidiases (thrush), Sore throat and a Croaky voice be avoided in inhaler usage
Use a spacer
Asthma treatment
1st choice = β2 adrenergic agonists,
e.g. salbutamol – (SABA) for fast relief
e.g. salmeterol, formoterol – long duration of action (LABA) - for prevention
Combine with anti-inflammatory – e.g. inhaled corticosteroid.
Cys-leukotriene receptor antagonists (e.g. montelukast)
COPD treatment
Muscarinic acetylcholine receptor antagonists used as there is significant cholinergic tone.
Long-acting bronchodilators used
Can combine muscarinic antagonists and β2-agonists
Glucocorticoids generally ineffective
Long-term oxygen therapy
What are eicosanoids?
20 carbon fatty acids (eicosanoic acid = a fatty acid with 20 carbons)
Prostaglandins (PG)
Thromboxanes (TX)
Leukotrienes (LT)
Lipoxins (LX)
Action of eiocosanoids
Stomach - reduce acid secretion and increase mucus and bicarbonate secretion
Kidney - regulates blood flow and renin release
Lungs - bronchoconstriction
Uterus - smooth muscle contraction (synthetic analogue drugs used in induction of labour and termination of pregnancy)
Eye - Regulates intraocular pressure (synthetic analogue drugs used in treatment of glaucoma)
Platelets - Regulates aggregation (some eicosanoids increase and some decrease)
Pro-inflammatory - Vasodilation; increase vascular leakage caused by other mediators weal and flare
Sensitise pain sensory neurons hyperalgesic
Regulate temperature set-point fever
Anti-inflammatory - Decrease lysosomal enzyme release and toxic oxygen metabolites in neutrophils, inhibit release of histamine from mast cells
Where do eicosanoids come from?
Arachidonate is released by a specialized phospholipase A2
Arachidonate is normally part of membrane phospholipids
What can Arachidonic acid become?
12-HETE (chemotaxin)
lipoxins
Prostaglandins and Thromboxane
Leukotrienes
What do leukotrienes cause? (LTC,D,E4)
Bronchoconstriction
Vasodilation (but coronary vasoconstriction)
Increased vascular permeability
↑ Mucus secretion
What is the action of leukotriene (LTB4)
On Neutrophils:
↑ adhesion molecules, ↑ superoxide anions and release of granule enzymes
On Macrophages:
↑ cytokine production,
↑ proliferation
What is the cyclo-oxygenase pathway?
Arachidonic acid > Cyclic peroxidases > Prostaglandins or Thromboxane
What are the types of prostaglandins?
PGF2α - Uterine contraction
PGI2 - Vasodilator, inhibits platelet aggregation, Renin release
PGD2 - Vasodilator, inhibits platelet aggregation, Relaxes gut and uterine muscle
PGE2 - Vasodilator, inhibits platelet aggregation
TXA2 - vasoconstrictor, ↑ platelet aggregation
What can and what happens when you inhibit cyclo-oxygenase?
NSAIDs (Non-Steroidal Anti-Inflammatory Drugs) are inhibitors of COX. e.g. aspirin, ibuprofen.
Vasoconstriction, Decrease in permeability, Desensitise pain fibres, temp. control.
Unwanted effects of inhibiting Cyclo-oxygenase
Stomach:
↓ mucus and bicarbonate secretion;
↑ acid secretion (module 5)
Kidney:
Can get nephrotoxicity (module 7)
Skin rashes – idiosyncratic (see ADRs)
Cardiovascular:
Effects on vasodilation and platelet aggregation (module 3)
Types of cyclo-oxygenase
Cyclo-oxygenase 1 (COX1)
Physiological roles
Stomach
kidney
Constitutive
Cyclo-oxygenase 2 (COX2)
Inflammatory roles
Induced during inflammation
Describe aspirin binding to COX
irreversible binding
On platelets,
Why use corticosteroids to inhibit arachidonic acid formation?
activate lipocortins > inhibit cPLA2
Down-regulate COX-2 synthesis
Many other anti-inflammatory actions
What is compliance?
Extent to which patient behaviour matches prescribers recommendations
What is adherence?
Extent to which patient behaviour matches the agreed recommendations from the prescriber
What is concordance?
Discussion between equals to come to an agreement
Non-adherence is…
Delay in seeking care
Non-participation in health programmes
Breaking an appointment
Failure to follow post-treatment instructions (failure to receive medication, taking incorrect dose or at the wrong time, and stopping treatment early)
Types of non-adherence:
Erratic non-adherence
Intelligent non-adherence
Unwitting non-adherence
Erratic non-adherence: Unintentional, forgetfullness
Intelligent non-adherence: Intentional wise decision
Unwitting non-adherence: Misunderstanding
Factors that influence adherence
Social & economic
Healthcare system
Therapy related
Condition related
Patient related
Health belief model and non-adherence
Perceived susceptibility
Perceived severity
Perceived benefits
Perceived barriers
Cues to action
self-efficacy
What is self efficacy
Confidence in one’s ability to adhere in difficult situations
a) meaningfulness, (b) competence, (c) impact, and (d) self-determination
Specific techniques to improve adherence
Patient education
Medication regimen management
Pharmacist consultation
Cognitive behavioural therapy (CBT)
Financial incentives
How to check for rotation on X rays
Does the thoracic spine align in the centre of the sternum and between the clavicles?
Are the clavicles in the same level? Look for the trachea, which should be in the midline.
How to know if an x-ray is over penetrated or under penetrated?
If under penetrated, the thoracic vertebrae will not be clearly visible.
Over, loss of low density regions
Was an x-ray taken under full inspiration
9 - 10 posterior ribs should be visible in full inspiratory view. When X-ray beams pass through the anterior chest on to the film (AP view), the ribs closer to the film (posterior) are most apparent. A really good film will show anterior ribs too, there should be at least 5 - 6 anterior ribs to qualify as a good inspiratory film.
CT vs MRI
CT
X-rays
Fractures, tumours, cancer, internal bleeding, organs.
Risks: unborn babies, radiation, reaction to dyes
Faster, cheaper
MRI
Radio waves
Soft tissues, joints, brain, heart, soft tissues
reaction to magnets, noisy, claustrophobia
Cant have implants, minute details in soft tissues
What is a V/Q lung scan
V - inhaled technetium
Q - injected technetium
Scanned to image
Ultrasound
Soundwaves reflected by stuctures - bone and gas absorbs all sound. No safety concerns
Positron emission tomography
Positron emitting nuclide taken up by most active tissues
Single photon emission computed tomography
gamma emitting nuclide
What imaging would you use for chest, skull, chest wall, urt
chest - X-ray
skull - CT
chest wall Ultrasound
URT Bronchoscopy
What does consolidation look like on an x-ray
ill defined increased density
What does interstitial damage look like on an x-ray
Fine or coarse reticular opacities or small nodules
What does atelectasis look like on an x-ray
volume loss and increased density
Physical examination findings of pneumothorax
Inspection - breathless, unilateral hyperinflation, pain, laboured breathing
Palpation - deviated trachea away from affected side, decreased expansion on affected side
Percussion - Hollow
Auscultation - Decreased breath sounds on affected side
Physical examination findings of consolidation
Palpation - Increased vibration over affected lobe
Percussion - Dull note
Auscultation - Bronchial breath sounds
Physical examination findings of Pneumonia
Inspection - Fever, breathless
Percussion - Dull note
Auscultation - Bronchial breath sounds
Physical examination findings of COPD
Inspection - Hyperinflation
Percussion - Hyper-resonant
Auscultation - Decreased breath sounds, wheezes, crackles at base
Peak Expiratory Flow (PEF)
Maximal speed of airflow (L/min) as the patient exhales
List all the measurement taken in spirometry
VT = Tidal Volume
IRV = Inspiratory Reserve Volume
ERV= Expiratory Reserve Volume
RV = Residual Volume
VC = Vital Capacity
TLC = Total Lung Capacity
FRC = Functional reserve volume
Inspiratory Capacity = VT + IRV
Functional Residual Capacity = ERV + RV
What is FVC
Maximal amount of air that the patient can forcibly exhale after taking a maximal inhalation
FEV1
Volume exhaled in the first second
Volume-Time graphs in restrictive disease (fev fvc)
A Low FVC
Low FEV1 but proportional
But FEV1 /FVC ratio ≥ 70%
Volume-Time graphs in obstructive disease
FVC nearly normal
FEV1 markedly reduced
The FEV1 / FVC ratio < 70%
In a flow volume loop, how does airflow obstruction appear
Bend in the downward line of inspiration, normal shape of expiration
In a flow volume loop, how does airflow restriction appear
Similar shape, just smaller
In a flow volume loop, how does interstitial lung disease appear
Very narrow graph
What is a paternalistic doctor patient model
Doctor is in charge, less anatomy
What is a informative doctor patient model
Doctor provides the information for decision making
What is a interpretive doctor patient model
Provides information and the rationale
What is a deliberative doctor patient model
Good conversation to determine a plan of action
What does the liver mainly store
Major glycogen reserve
What does adipose tissue mainly store
Stores lipids primarily as triglycerides
What does Skeletal muscle mainly store
Substantial glycogen reserves
Half of all protein in the body
What causes muscle wasting
The difference between nitrogen input into the body (dietary protein) and nitrogen excretion mainly as UREA
Two main pathways of proteolysis
1) lysosome pathway degrades extracellular and cell-surface proteins via endosomes and most proteins via autophagosome (common in starvation)
2) ubiquitin-proteasome pathway degrades proteins from the cytoplasm, nucleus and ER
Describe the lysosome protein degradation pathway
Membrane bound
Have a low pH
Contain multiple proteases:
Cathepsins
cysteine proteases
serine proteases
aspartate (aspartyl) proteases
Describe the ubiquitination pathway
(ubiquitin activating enzyme (E1) -> ubiquitin conjugating enzyme (E2) -> ubiquitin Ligase (E3)) -> ubiquitination of target protein -> proteasome degradation
What ubiquitin ligase is involved in muscle wasting?
With muscle
wasting the E3s: MAFbx (Atrogin 1)
MuRF-1
Describe gluconeogenesis
Glycolysis “in reverse”
addition of aa’s to TCA cycle constituents
Describe aa degradation
Amine group -> Urea
Carbon skeleton -> glucose, CO2 + h20, Acetyl CoA, Ketone bodies
What is urea?
Urea is small, neutral, non-toxic, very water-soluble
Nitrogen excreted as urea
Why have urea?
Ammonium ions are toxic; >1mM causes encephalopathy
How is urea produced?
Aspartate formed via transamination of oxaloacetate
Oxidative deamination of glutamate to alpha-ketoglutarate
Why has TB not been eradicated?
Much of the initial improvement in TB ratesin more developed countries was related to improvements in housing, nutrition and access to treatment, but these issues are still present in many countries that are less developed
Several strains of TB bacteria have developed resistance to 1 or more anti-TB medications, making them much harder to treat
The BCG vaccination is effective against severe forms of the disease, such as TB meningitis in children, but it’s not as effective against all forms of TB
Theglobal epidemic of HIV that began in the 1980s has led to a corresponding epidemic of TB cases because HIV weakens a person’s immune system, making them more likely to develop a TB infection
The rapid growth of international travel has helped the infection to spread
Risk factors of TB
Persons who have been recently infected with TB bacteria
Persons with medical conditions that weaken the immune system
Latent TB Symptoms
No signs or symptoms
Host defences prevent growth of bacteria
Not infectious, cannot pass infection on
Skin or blood test positive
Normal chest X-ray
TB symptoms
Primary infection or activation of latent TB
Signs and symptoms, patient feels sick
Can spread infection
Skin or blood test positive
May have abnormal chest X-ray or sputum sample
Needs treatment
Diagnostic tests for TB
Skin Test
Microbiological sampling
Blood Test
Molecular Testing
Imaging
Skin test for TB
TST – tuberculin skin test
Also called Mantoux test
0.1ml of tuberculin derived protein injected into skin of forearm
Positive test = 5mm or larger
Microbiological Sampling for TB
Sputum analysis (x3)
Slender rods; aerobes
High content of complex lipid- ID by acid fast stains
Growth is slowed by acidic pH, presence of long chain fatty acids, anaerobic conditions
Cultures to check for drug susceptibility
Staining characteristic of mycobacterium
Mycobacteria have the unusual property of retaining basic dyes when treated with acidic solutions.
The most abundant wax,mycolic acid, is an α-alkyl-hydroxy fatty acid covalently linked to the cell wall.
Blood tests for TB
Blood tests - Interferon-Gamma Release Assays (IGRAs)
White blood cells from infected persons release IFN-g upon exposure to antigens derived from M. tuberculosis
Mycobacterium causing TB
tuberculosis, bovis, africanum
Active TB symptoms
A persistentcough
Constant fatigue
Weight loss
Loss of appetite
Fever
Coughing up blood
Night sweats
Reactivated TB symptoms
gradual onset of anorexia, weight loss, fever (low grade, remitting), night sweats
Granulomatous inflammation
A form of chronic inflammation characterised by groups of activated macrophages, T lymphocytes and sometimes necrosis
It is the body’s attempt to section off an offending agent that is difficult to eradicate – the attempt to eradicate is often damaging to healthy tissue
Activated macrophages can begin to resemble epithelial cells – epithelioid cells
Some macrophages fuse together to form Langhans giant cells
Older granulomas have fibroblasts and collagen
Hypoxia causes necrotic core
Granulomatous inflammation in TB
In TB ONLY: caseous necrosis; yellow-white cheese-like (gross) amorphous granular lysed cells with no cell outlines/architecture.
Pathogenesis of TB
Inhaled mycobacteria engulfed by macrophages
Manipulate endosomes (pH and maturation)
Defective phagolysosome formation
Mycobacterial proliferation in macrophages
Mild flu symptoms/ asymptomatic
Cell mediated immune response
Macrophages drain to lymph nodes
Antigens presented to T cells
T cells converted to Th1 cells
Th1 cells activate macrophages (gamma IFN)
Monocytes recruited free radicals and ROS
Epithelioid macrophages
Ghon focus
Primary lesion of granulomatous inflammation
Usually subpleural
Ghon Complex
A Ghon focus & infection of adjacent lymphatics and hilar lymph nodes
When a Ghon’s complex undergoes fibrosis and calcification it is called aRanke complex
TB with cavitation
Once the TB bacilli become reactivated, they rapidly destroy the lung tissue around the granuloma. This causes major damage to the tissue, which gets destroyed
Spread of TB
Caseating tubercle erodes into lung vasculature
Systemic dissemination to any organ via pulmonary vein (commonly liver, kidney, spleen)
If pulmonary artery involved (ie lymph drainage to right heart): miliary TB of lung
Neoplasm
Tumour
Hyperplasia
In these growths, cells have normal appearance but are abnormal in that they contain excessive numbers of cells
Metaplasia
In these growths, normal cells of one differentiated type displaced by another type of differentiated cells that may not normally be present at that specific location
Dysplasia
Dysplastic growths contain cells that are cytologically abnormal:
Tumour suppresor gene example
P53
Oncogene
a cancer-inducing gene - a gene that can transform cells
‘Six’ steps of cancer diagnosis/progression defined at the molecular level:
- Self-sufficiency of growth, e.g. overproducing GFs and/or GFR.
- Do not respond to usual growth inhibitory signals, e.g. at cell cycle checkpoints.
- Evasion of apoptotic mechanisms, e.g. mutation of p53.
- Immortalisation, e.g. loss of telomere shortening after chromosome replication.
- Neoangiogenesis, e.g. overproduction of VEGF to stimulate growth of new blood vessels.
- Invasion and metastasis, e.g. alterations in production of cellular adhesion molecules.
Staging tumours
T0 = breast free of tumour
T1 = lesion <2 cm in size
T2 = lesion 2-5 cm
T3 = skin and/or chest wall involved by invasion
N0 = no axillary nodes involved
N1 = mobile nodes involved
N2 = fixed nodes involved
M0 = no metastases
M1 = demonstrable metastases
MX = suspected metastases
Symptoms of lung cancer
Coughing,
Weight loss,
Shortness of breath,
Chest pain,
Hemoptysis (coughing up blood, or sputum that is streaked with blood), and other non-specific symptoms including: fever, weakness, and lethargy.
Rarely, patients may present with difficulty swallowing or wheezing.
Paraneoplastic syndromes
Most endocrine are related to Small Cell Lung Cancer:
Cushings syndrome (ectopic adrenocorticotropic hormone ACTH)
Inappropriate ADH secretion (low Na)
Hypercalcaemia (PTH) -squamous
Screening Test for Early Detection of Lung Carcinoma
Early CDT-Lung is a blood test enabling the early detection of lung cancer.
Types of lung cancer
Small cell lung cancer - small cell carcinoma
Non-small cell lung cancer - squamous, adenocarcinoma, large cell carcinoma
Small cell lung cancer treatment
Most aggressive
limited - chemo, radiation, prophylactic cranial radiation
extensive - chemo, palliative radiation
Non small cell lung cancer treatment
80% of all lung cancers
Complications of lung cancer
30% presenting with symptoms of metastatic disease eg: fracture (bone), CNS symptoms (brain), jaundice (liver).
Local spread to nodes characterised by clinical syndromes:
SVC syndrome (compression from paratrachial nodes)
Horners syndrome (cervical sympathetic chain) etc.
