Respiratory system Flashcards
3 components of the upper respiratory tract
Nasal cavity
Pharynx
Larynx
Functions of nose
- Temperature of inspired air
- Humidity
- Filter function
- defence function; cilia take inhaled particulates backwards to be swallowed
The anterior narea open into the enlarged…
- Vestibule (skin lined, stiff hairs)
- Surface area of the nose (doubled by turbinates)
What do turbinates create?
Superior meatus
Middle meatus
Inferior meatus
Superior meatus
Olfactory epithelium
Cribiform plate
Sphenoid sinus
Middle meatus
Sinus openings
Inferior meatus
Nasolacrimal duct
What are the paranasal sinuses?
Evagination of mucous membrane from the nasal cavity.
Pneumatised areas of the frontal sinus, maxillary sinus, ethmoid sinus and sphenoid bones
How are the paransal sinuses arranged?
In pairs
Frontal sinuses (location and nerve supply)
Frontal sinuses are found within frontal bone and midline septum over the orbit and across superciliary arch.
Nerve supply: opthalmic division of V nerve
Maxillary sinuses (location, shape, structure)
Located within the body of the maxilla.
Pyramidal shape.
Base is lateral wall of the nose, apex is zygomatic process of the maxilla, roof is the floor of the orbit, an floor is the alveolar process.
Open into the middle meatus, sinus drain into nasal cavity through the hiatus semilunaris.
Ethmoid sinuses (location, features and nerve supply)
Between the eyes
Semilunar hiatus of the middle meatus
Labyrinth of air cells
Nerve supply - ophthalmic and maxillary V nerve
Sphenoid sinuses
Medial to the cavernous sinus
Inferior to the optical canal + pituitary gland
Empties into the sphenoethmoidal recess, lateral to the attachment of the nasal septum.
Nerve supply - ophthalmic V.
What is the pharnynx?
Fibromuscular tube lined with epithelium
Which kind of epithelium lines the pharynx?
Squamous and columnar ciliated
with mucuous glands
Nasopharynx is bounded by…
Base of skull Sphenoid rostrum C-spine Posterior nose (choana) Inferiorly at soft palate opens to oropharynx
Components of nasopharynx
Eustachian tube orifices (lateral wall) which supply air to middle ear and thus equalise pressure.
Pharyngeal tonsils on posterior wall.
Oropharynx components and their anatomical positions
Soft palate anteriorly.
Palatine tonsils on the lateral walls; tonsils in-between the palatoglossal walls and palatopharyngeal fold.
Inferior to hyoid bone.
Function of larynx
Valvular functions: prevents lipids and foods from entering lungs
Structure of larynx
Rigid structure with 9 cartilages and multiple muscles.
How are vocal chords changed?
Arytenoid cartilages rotate on the cricoid cartilage to change vocal chords.
What specifically prevents food going down into the lungs
Epiglottis
Main nerves of laryngeal innervation (more detail in further flashcards)
The vagus nerve (X cranial nerve)
Divisions of vagus nerve in laryngeal innervation
Vagus divides into superior laryngeal nerve and recurrent laryngeal nerve.
Superior laryngeal nerve
- source
- where does it go to
Inferior ganglion
Lateral pharyngeal wall, which divides into interal (sensation) and external (cricothyroid muscle)
Recurrent laryngeal nerve
- function
- divisions and the course of each division
Main motor function - all muscles except cricothyroid.
Left RLN: lateral to arch of aorta, loops under aorta, ascends between trachea and oesophagus.
Right LRN: Right subclavian artery, plane between trachea and oesophagus.
3 main components of the lower respiratory tract
1) trachea
2) primary bronchi
3) lungs
Thoracic cage (anatomical stuff)
Sternal angle at level of carina
Manubrium sternal joint = 2nd rib. In the second intercostal in midclavicular line you can stick chest drain.
Trachea features
- Where does it span to and from
- What vertebral level is the division of main left and right bronchi
- Epithelium
Spans down from larynx to the carina; the division oof the main left and right bronci (5th thoracic vertebra, T5)
Pseudostratified, ciliated, columnar epithelium with goblet cells
Semicircular cartilages
What is the name of the division of main left and right bronchi?
Carina
Difference between left and right bronchi?
Right main bronchus is shorter and wider while the left bronchus is longer and narrower. The right bronchus is more vertical compared to the left bronchus.
Lobar bronchi
Right - 3:
- Upper lobe
- Middle lobe
- Lower lobe
Left - 2:
- Upper lobe and lingular
- Lower lobe
Left is smaller due to accomodating the cardiac structures
Segmental branches/bronchi
Right:
upper lobe => apical, anterior, posterior
middle lobe => medial and lateral
Lower lobe => apical, anterior, posterior, medial, lateral
Left:
upper lobe => apico-posterior, anterior
lingular => superior and inferior
Lower => apical, anterior, posterior, lateral
Acinus
The acinus is a small saclike cavity in a gland that is supplied with air from one of the terminal bronchioles. There are ducts (short tubes with multiple alveoli).
Interconnections between alveoli:
pores of Kohn.
Types of cells in alveoli
Type I pneumocytes
Type II pneumocytes
Type I pneumocytes
barrier across which gas exchange occurs
Type II pneumocytes
Surfactant produces.
Surfactant decreases surface tension and keep alveoli open. Regenerate and replace damaged cells.
Other components of alveoli:
- Alveolar macrophages
- Basement membrane
- Interstitial tissue
- Capillary endothelial cell
What does lung innervation supply?
Controls many aspects of function => smooth muscle tone, mucus gland secretion, vascular permability, blood flow
Sympathetic lung innervation results in …
Bronchodilation
Parasympathetic lung innervation result
Bronchoconstriction
Pleura of lungs
2 main layers of mesodermal origin;
- Visceral
- Parietal
Visceral layer
Applied to lung surface
Autonomic innervation
Parietal layer
Applied to internal chest wall
Pain sensation
Pulmonary circulation
Left and right pulmonary arteries run from the right ventricle.
There are 17 orders of branching.
Elastic and non elastic, muscular arteries. Arterioles and capillaries.
How much gas is respiratory pump required to move?
5L/min
Which parts are always involved in the respiratory pump
Bones muscles pleural peripheral nerve airways
Respiratory pump and pressure
Negative intra-alveolar pressure has to be generated to allow inspiration of air. Diaphragm contracts in inspiration, becoming flat and increasing the tidal volume of lung.
Bony thorax function
Bony structure supports respiratory muscles and protects lungs. Helps support rib movement.
Describe the process of inspiration
- The diaphragm contracts causing its dome to move downards thereby enlarging the thorax and increasing its volume
- Simultaneously, activation of the motor neurones in the intercostal nerves to the EXTERNAL intercostal muscles causes them to contract, resulting in an upward and outward movement of the ribs and a further increase in thoracic volume
- As the thorax expands the intrapleural pressure is being lowered and the transpulmonary pressure becomes more POSITIVE, resulting in lung expansion since the force acting to expand the lungs (i.e. transpulmonary pressure) is becoming greater than that of the elastic recoil exerted by the lungs
- The lung expansion results in the alveolar pressure becoming negative which results in an inward airflow
- At the end of inspiration, the chest wall is no longer expanding but has yet to start passive recoil, since lung size is not changing and the glottis is open at this point.
- Alveolar pressure = atmospheric pressure, since the elastic recoil of the lungs has been balanced by the transpulmonary pressure - resulting in no airflow
Describe the process of expiration
- At the end of inspiration, the motor neurones to the diaphragm and external intercostal muscles decrease their firing so these muscles can relax; the diaphragm ascends thereby decreasing thoracic volume
- As they relax, the lungs and chest walls start to passively collapse due to elastic recoil - this is because the muscle relaxation causes the intrapleural pressure to increase, thereby decreasing the transpulmonary pressure so it becomes more negative.
- As the lungs become smaller, air in the alveoli becomes temporarily compressed resulting in an increase in alveolar pressure i.e it becomes more positive and exceeds atmospheric pressure resulting in air flowing outwards
Muscles of inspiration
Diaphragm = 70% of volume change
External intercostals = lift ribs 2-12 and widen thoracic cavity
Scalenes lift ribs 1-2
Pectoralis major lifts ribs 3-5
Sternocleidomastoid elevates the sternum
Nerves involved with the lungs
MOTOR
Diaphragm C3, 4, 5
Thoraco-lumbar nerve roots
SENSORY
- Sensory receptors assessing flow, stretch etc.
- Afferent via vagus (X cranial nerve)
Static lungs
Both chest wall and lungs have elastic properties and a resting unstressed volume.
Changing this volume requires force, and release of this force leads to a return to the resting volume.
What do terminal bronchioles lead to?
Respiratory bronchioles (at the centre of acinus), alveolar ducts and alveoli.
Dead space definition
volume of air not contributing to gas exchange
Pre-inspiration/end expiration volume of air
500mls
How much of 500mls go to blood (in ml)
350
How is alveolar dead space increased?
Very rapid breaths increase DS and under ventilates the alveoli.
Vice versa - big breath hyperventilate and over ventilate alveoli.
How many capillaries per alveolus?
1000 Each RBC (erythrocyte) can come into contact with multiple alveoli.
At what point is Hb fully saturated
At rest 25% of the way through the capillary
What does perfusion of capillaries depend on
Pulmonary artery pressure
Pulmonary venous pressure
Alveolar pressure
Pulmonary vascular resistance
Certain pulmonary arteries have smooth muscle within their walls
Hypoxic pulmonary constriction (which is the opposite from systemic circulation)
Hypoxic pulmonary vasoconstriction
Blood vessels divert blood to the more oxygenated parts of the lungs away from [low O2] areas, or areas with collapsed airways.
PaCO2 definition
arterial CO2
PACO2 definition
alveolar CO2
PaO2 definition
arterial O2
PAO2 definition
alveolar O2
PIO2
Pressure of inspired oxygen
V’A
Alveolar ventilation
V’CO2
CO2 production
HCO3-
bicarbonate
Why are O2/Hb dissociation curves non-linear
More binding of O2 and Hb facilitates further binding due to changes in Hb binding sites.
=> sigmoidal S shape
Alveolar gas equation
PAO2 = PiO2 - PaCO2/R
R = respiratory quotient
Why is the alveolar gas equation important?
Important for patients in the ICU to know how much oxygen to give them.
What is the pressure of inspired O2
21 kPa
What is the atmospheric pressure of O2
100kPa
Causes of hypoxeamia (low blood O2)
Alveolar hypoventilation
Reduced PIO2
V/Q mismatch
Diffusion abnormality
CO2 equation
PaCO2 = k V’CO2/V’A
What shape is CO2/Hb dissociation curve?
Linear
3 ways CO2 is carried
- bound to Hb (approx 23% of CO2)
- dissolved in plasma
- As HCO3- (bicarbonate)
What is PaCO2 directly proportional to? What is it inversely proportional to?
Directly p to amount of CO2 produced
Inversely p to alveolar ventilation
Physiological causes of high [CO2]
V’A reduced
Increased dead space by rapid shallow breathing
Increased dead space by V/Q mismatching
Increased CO2 production
Why is acid-base balance controlled carefully?
Normally body acids and bases are regulated to ensure the pH of the extracellular fluid is within a narrow range to ensure optimal function (e.g. of enzymes)
Normal range of [H+]
34-44nmol/L
optimal = 40nmol/L
Is HCO3- a strong or weak base
weak
Is H2CO3 a strong or weak acid?
Weak
Which is a particularly important buffer in the blood?
Carbonic acid/bicarbonate buffer
CO2 is under predominant ??? control
respiratory
HCO3- is under predominant ??? control
renal
pH of bodily fluids is regulated by three main buffering systems:
- intracellular and extracellular buffers
- the lungs eliminating CO2
- renal HCO3- reabsorption and H+ elimination
Acid continually produced by …
metabolic processes
Carbonic acid equilibrium
CO2 + H2O <=> H2CO3 <=> H+ and HCO3-
Hendersson-Hasselbach equation
pH = 6.1 + log 10 [[HCO3-]/[0.03*PCO2]]
4 main acid-base disorders are:
- Respiratory acidosis
- Respiratory alkalosis
- Metabolic acidosis
- Metabolic alkalosis
Respiratory acidosis
Increased PaCO2
decreased pH
mild increased HCO3-
Respiratory alkalosis
Decreased PaCO2
increased pH
mild decrease HCO3-
can be caused by hyperventilation
Metabolic acidosis
reduced bicarbonate
decreased pH
Metabolic alkalosis
increased bicarbonate
increased pH
acidotic
not enough CO2 removed
Acute inflammation
- Vasodilation leads to excretion of plasma, including antibodies.
- Activation of biochemical cascades e.g. complement and coagulation cascades
- Migration of blood leukocytes into the tissues; mainly neutrophils but also some monocytes.
Double edged sword of inflammation
Inflammation is the body’s defence against infection and a hostile environment. But many of us die of causes caused by inflammatory processes (e.g. pneumonia).
Inflammation-mediated tissue damage in the lung (examples)
COPD (chronic obstructive pulmonary disease).
Acute Respiratory Distress Syndrome.
Brionciesctasis
Interstitial lung disease
Asthma
COPD
Caused by cigarette smoking and fossil fuels.
Casued by the action of neutrophils on the lung: leads to destruction of the alveolar membrane.
Proteases degrade elastase and cause collapse of airways.
Acute respiratory distress syndrome
Respiratory failure
Water and neutrophils fill the alveoli causing lungs to appear more grey on an X-ray.
Any condition that causes inadequate tissue oxygenation may precipitate ARDS e.g. trauma, lung infetion, sepsis, surgery etc.
Pathophysiology of ARDS
- Endothelial leak (leaking to extravasatation of protein and fluid)
- Lungs - reduced compliance makes lungs stuff, increasing shunting.
- Heart - pulmonary hypertension, reduced cardiac output
- Hypoxia
Where is acute inflammation initiated
Initiated in the tissues by epithelial production of hydrogen peroxide when it is damaged. Hydrogen peroxide is natural bleach and attracts neutrophils (haemotaxic effect).
How is the acute inflammation initial response amplified?
Initial response amplified by specialist macrophages.
Specialist macrophages in the acute inflammation response
- Kupffer cells (liver)
- Alveolar macrophages (lungs)
- Histiocytes (skin, bone)
- Dendritic cells
(acute inflammation) Response to pathogens or tissue injury involves the recognitio of:
- PAMPs (pathogen-associated molecular patterns) which recognise pathogens
- DAMPs (damage-associated molecular patterns) which recognise damage
What are pattern recognition receptors (PRRs)
These receptors recognise new pathogens and are involved in signalling and endocytosis.
Examples of Pattern Recognition Receptors (PRRs)
Toll-like Receptors which recognise endogenous mediators of inflammation
Nod-like receptors (NLRs)
Endocytic PRRs
=> mannose receptors
=> glucan receptors
=> scavenger receptors
What are alveolar macrophages similar to cytochemically and morphologically
mature tissue macrophages
Where do alveolar macrophages arise from?
monocytes
foetal macrophages populate lungs to form alveolar macrophages
3 types of macrophages and their function
M1 - host defence; produce Th-cells and NK cells
M2a - tissue repair; stimulating fibroblasts
M2b - resolution - healing, sending away immune cells
Brief overview of neutrophil functions
Identification Activation Adhesion Migration/chemotaxis Phagocytosis Bacterial killing
Neutrophils + activation
Stimulus-response coupling; matching immune response to stimulus.
Allowing phagocytosis of bacteria.
Signal transduction pathway including calcium, protein kinases, phospholipases, G proteins.
Neutrophils and migration
They are able to detect a concentration gradient of bacterial products or chemokines and move along it
Neutrophils + bacterial killing
Lysosomal enzymes in granules (cathepsins, elastase)
Reactive oxygen species
ROS generated by a membrane enzyme complex - the NADPH oxidase
Pack-year
1 pack year = smoking 20 cigarettes per day for 1 year
What is spirometry
A test used to assess how well your lungs work by measuring how much air you inhale, how much you exhale and how quickly you exhale
What is ACOS
Asthma and COPD overlap syndrome
Regulation of airwys smooth muscle tone
Airway smooth muscle is regulated, contracting and relaxing to regulate airway diameter. This is important in diseases such as COPD and asthma.
It is regulated by inflammation and the autonomic
Regulation of airwys smooth muscle tone
Airway smooth muscle is regulated, contracting and relaxing to regulate airway diameter. This is important in diseases such as COPD and asthma.
It is regulated by inflammation and the parasympathetic NS.
Contractile signals cause increase in intracellular calcium in smooth muscle, which activates actin-myosin contraction.
Parasympathetic bronchoconstriction
Vagus nerve neurons terminate in the parasympathetic ganglia in the airway wall. Short post-synaptic nerve fibres reach the muscle and release acetylcholine, which acts on muscarinic receptors of the M3 subtype on the muscle cells. This stimulates airway smooth muscle constriction.
Excessive bronchoconstriction
EB narrows the airway in asthma and in COPD (and other like bronchiectasis).
Therefore, inhibition of the parasympathetic nervous system will be beneficial.
Drug action to inhibit parasympathetic nervous system to prevent excessive bronchoconstriction
Drugs block the M3 rceptor, and are called ANTI-CHOLINERGICS or ANTI-MUSCARINICS.
Short acting: ipratropium bromide (atrovent).
Long acting: LAMAs such as tiotropium, glycopyrrhonium.
Anti-cholinergics
SAMA (short acting muscarinic antagonist)
LAMA (long acting muscarinic antagonist)
Short acting muscarinic antagonists (SAMAs)
Ipratropium bromide exists as an inhaler and can be used as inhaled treatment to relax airways in asthma and COPD.
Its not that effective, and is much less used since LAMAs were invented.
It is still used in high dose in nebulisers as part of acute management of severe asthma and COPD.
Long acting muscarinic antagonists (LAMAs)
Have a long duration of action (many hours), often given once a day.
Increase bronchodilation and relieves breathlessness in asthma and COPD.
Seem to reduce acute attacks as well.
SABAs and LABAs
Short-acting (salbultamol) and long-acting (formoterol, salmeterol)
Acute rescue of bronchoconstriction
Prevention of bronchoconstriction
Reduction in rates of exacerbations
Given with steroids in asthma, often without steroids in COPD.
LABA often given with LAMA in COPD.
Mechanism of action of Beta 2-agonists
B2-aginist attaches to Beta-2 receptors on airway muscle. This has an affect on the G-protein and stimulates adenylyl cyclase which converts ATP into cAMP. Protein kinase is converted to pLA. This all causes RELAXATION of airway smooth muscles.
Adverse effects of B2-agonists
- Raising cAMP may activate Na/K exchange pump driving cellular influx of potassium
- Tachycardia - increased HR
- Hyperglycaemia: loss of insulin sensitivity, increased liver glucose release, OD of salbutamol
- If patients have acute asthma exacerbations give salbutamol nebulisers. Blood test should show low K levels since salbutamol drives potassium into cells. High K - renal failure.
Relieving inflammation may involve ???
Treating infection may involv ???
Preventing excess mucus may involve ???
- steroids
- antibiotics
- LAMAs
Immediate Treatment of an Asthma attack
O2 up to 60% (CO2 retention is not usually a problem)
Salbutamol nebuliser 5mg
Prednisolone 30-60mg
Magnesium or aminophylline IV
Non-respiratory functions of the lungs
Synthesis, activation and inactivation of vasoactive substances, hormones, neuropeptides.
2 types of host lung defence
- intrinsic
- innate
intrinsic host defence
always present Physical and chemical barriers - Apoptosis - Autophagy (removal of cells) - RNA silencing - antiviral proteins
innate host defence
Induced by infection
- interferon
- cytokines
- macrophages
- NK cells
Adaptive immunity
Tailored to a specific pathogen (T cell, B cell)
Molecules secreted from the epithelium during host defence:
- Antiproteinases
- Anti-fungal peptides
- Anti-microbial peptides
- Surfactant -A and -D
What do Surfactant A and D do
Opsonise pathogens for enhanced phagocytosis (bind to the pathogen and make it more visible for immune response)
Cellular physical barrier
Airway epithelium
What do epithelial cells do in the upper respiratory tract?
Epithelial cells secrete granules from secretory cells into the pericellular lining fluid. A mucin layer forms on the apical surface. The secretory components also come from the submucosal gland and move through the duct to the pericellular fluid. Within the specific cell types, specific genes and proteins are produced.
Two types of peripheral lung tissue in the lower tract
Type I: biosynthetic, thin, next to capillaries and allows for gas exchange
Type II: secrete host defence and surfactant which coats the lungs (helps to keep the lungs open due to surface tension)
What kind of epithelium is in bronchus? What other components are there?
Pseudostratified ciliated epithelium Basal cells Goblet cells Submucosal gland and duct Inflammatory cells
What kind of epithelium is in bronchiolus?
Cuboidal ciliated epithelial
Cells in alveoli
Thin layer of tube cells
Type I and II pneumocytes
Type I pneumocytes
Allow for air diffusion by forming the barrier across which gas exchange occurs
thin squamous cells
Type II pneumocytes
innate defence cells and secrete protective molecules - important for surfactant production
What does airway mucus contain?
Airway mucus is a viscoelastic gel containing water, carbohydrates, proteins and lipids
What secretes mucus?
Submucosal glands and the goblet cells of the airway surface epithelium
Two different pathways of a cough as a defence reflex (nerves)
Afferent and efferent
Afferent limb - induces receptors within the sensory distribution of the trigeminal, glossopharyngeal, superior laryngeal and vagus nerves => go TOWARDS the CNS.
Efferent limb - includes the recurrent laryngeal nerve and the spinal nerves => goes AWAY from the CNS.
Infecctions targeting specific airway epithelial cells
Virus target expression of specific proteins. Recovery phase occurs as cell dies as a result. The epithelium can effect a complete repair after injury. The epithelium exhibits a level of functional plasticity. Cells can change phenotypes.
What happens when mucociliary transport is impaired?
Pulmonary diseases
Mucus plug/inflammation =severe disease
Blocking the airway in a patient with severe cystic fibrosis.
Residual volume
The volume of air that remains in the lungs after forced expiration
Total Lung Capacity
Total amount of air in thorax at full inspiration including the air you can’t get rid of at at max expiration
TLC= VC + RV
Inspiratory capacity
Maximum volume of air that can be inhaled following a resting state
IC = IRV + TV
Tidal volume
Amount of air that can be inhaled/exhaled during one respiratory cycle
Inspiratory reserve volume
Amount of air that can be forcibly inhaled after a normal tidal volume.
Expiratory reserve volume
The volume of air that can be exhaled forcibly after exhalation of normal tidal volume.
Vital capacity
The amount of hair exhaled after maximum inhalation
VC = TV + IRV + ERV
Function residual capacity
The amount of air in the lungs at the end of a normal exhalation
FEV1
Forced expiratory volume in 1 second
FVC
Forced vital capacity (total amount of air forced out)
FEF25
Flow at point when 25% of total volume to be exhaled has been exhaled
Peak expiratory flow (rate) - PEF
Single measure of highest flow during expiration. (L/min)
Effort dependent
Measured over time, giving a patient a PEF meter and chart.
Gas Dilution method
Measures of all air in lungs that communicates with the airways including residual.
Does not measure air in non-communicable bullae.
Gas dilution techniques use either:
- close-circuit helium dilution
- open-circuit nitrogen washout.
Usually the patient is connected at the end-tidal position of the spirometer, measuring FRC.
Total body plethysmography
Alternative method of measuring lung volume (Boyle’s Law) including gas trapped in bullae. From theFRC,patient “pants” with an open glottis against a closed shutter to produce changes in the box pressure proportionate to the volume of air in the chest. The volume measured (TGV) represents the lung volume at which the shutter was closed.
DL CO
diffusion capacity of lung for carbon monoxide
Causes of Low DL CO
COPD and emphysema
DLCO is an overall measure of the interaction of …
Alveolar surface area
Alveolar capillary pressure
Physical properties of the alveolar capillary interface
Capillary volume
Hb concentration and the reaction rate of CO and Hb.
COPD is a ? condition
progressive
Symptoms of COPD
Wheeze and shortness of breath on exercise
What is reduced during COPD?
Mid expiratory flows
3 overall phases of embryological development of the respiratory tract
- Conducting airways
- Units for gas exchange
- Blood supply
Stages of pulmonary development
Embryonic Pseudo glandular Canalcular Sacular Alveolar
Order the components of the respiratory system are developed
Bronchi Bronchioles Terminal bronchioles Respiratory broncioles Alveolar ducts Alveolar sac
Development of respiratory diverticulum
By the 5th week the lung buds enlarge to form right and left main bronchi. The oesophagotracheal septum develops and separates the trachea from oesophagus.
Where does the lung bud develop from
the foregut
How does separation of the two lung buds come about?
The fusion of esophagotracheal ridges to form the eosophagotracheal septum.
When the embryo is 5 weeks old, what is identifiable? What do these structures go on to form?
two primary lung buds. The lung buds go on to form their first subdivisions, with 3 lobar buds developing in the right lung bud and 2 lobal buds developing in the left.
What are the lung buds forerunners of?
The right upper, middle and lower lobes and the left upper and lower lobes.
What happens in the 8 week old embryo?
Development progresses as the lobar buds subdivide and form the bronchopulmonary segments.
What are lung buds lined by? How does it develop?
endodermally derived epithelium
What is the innervation of the lungs derived from?
Ectoderm
Which parts of the lungs is the mesoderm an origin
blood vessels
smooth muscle
cartilage
other connective tissue
week 5/6-17
pseudoglandular stage
What is formed during PG stage
Conductive airways are formed by progressive branching. Eventually 16-25 generations of primitive airways are formed.
Under what conditions do endodermal lung bugs undergo branching?
Only if they are exposed to bronchial mesoderm.
What is the rate and extent of branching of endodermal lung buds directly proportional to?
the amount of mesenchyme present
By how many weeks are all bronchial airways formed? What happens after this time in terms of further growth?
16
Further growth occurs by elongation and widening of existing airways
What happens by 13th week in terms of differentiation of the lung epithelium
cilia appear in the promixal airways
What is necessary for epithelial differentiation to occur?
Mesenchyme
week 16-25
Canalicular phase
What has already happened by the canalicular stage?
The gas exchange portion of the lung is formed and vascularised.
By week 20 there is differentiation of the …
type I pneumocyte
Capillaries begin to grow in close proximity to ..?
The distal surface of the alveolar cells
There is the appearance of ??? in type II alveolar cells.
What is the function of them?
lamellar bodies AKA inclusion bodies
Lamellar body is site of surfactant storage, prior to its release into the alveolar space.
What encompasses the period from 26 weeks til term?
The saccular stage / terminal sac
Saccular stage
There is a decrease in interstitial tissue and a thinning of the alveolar walls. As this stage progresses, there are recognizable Type I and Type II cells.
What does the stability of the lung at birth correlate to?
The number of lamellar bodies present
What happens if there is absence of surfactant?
The body can only maintain alveoli in an open state for a very short time.
Features of foetal lungs?
Shunting of blood from right to left
High pulmonary vascular resistance
Tissue resistance
Low systemic resistance
Where does blood travel to to get O2 instead of lungs
placenta
Foetal circulation
1 umbilical vein with oxygenated blood
2 umbilical arteries with deoxygenated blood
3 fetal shunts
3 foetal shunts
Ductus venosus
Foramen ovale
Ductus arteriosus
Ductus venosus
hepatic system
within liver - oxygenated blood from placenta moves through liver to inferior vena cava
Foramen ovale
between right and left atrium
Supplies developing brain, heart and rest of body
Ducus arteriosus
vein connects pulmonary artery to descending aorta
Since blood doesn’t need to go to lungs, some shunts across back into systemic circulation.
What happens with systemic circulation once cord is cut
The pressure in the systematic circulation increases and forms more pressure on the left side, thus closing the shunts in the liver and heart.
What can go wrong with foetal lungs/circulation
Persistant foetal flow circulation/persistent pulmonary hypertension of new born
Right to left shunt => hypoxia => pulmonary hypertension
What does hypoxia in newborn babies lead to?
Blue baby
blood doesnt attract enough oxygen into lungs; high pressure in lungs means there is less oxygenation and baby continues to be blue until intervened.
Fetal airways are distended with …
lung fluid
At the time of birth, what changes with lung fluid
Due to hormones and stress, the lung channels change from mainly secretory to mainly absorptive, so lung fluid is removed.
What is surface tension a measure of?
The force acting to pull a liquids surface molecules together at an air-liquid interface.
Why is surfactant useful for alveoli?
Alveoli are lined with fluid, which theoretically should cause them to collapse, but this doesn’t happen due to surfactant. Surfactant removes surface tension, allowing alveoli to expand. Surfactant allows homogenous aeration and maintenance of functional residual capacity.
Which cells produce surfactant?
Type 2 pneumocytes from 34 weeks gestation, dramatically increase in 2 weeks prior to birth
The first breath
Fluid is squeezed out of lungs by birth process (where lung channels change from secretory to absorptive). Adrenaline and stress cause increased surfactant release. Air is inhaled, and oxygen vasodilates pulmonary arteries, increasing pulmonary blood blow and decreasing resistance. Umbilical arteries constrict and ductus arteriosus constricts.
Antibodies
IgM - tetramers made at beginning of infection. Not specific.
IgGs - very specific. Target single epitopes.
IgE - involved in allergic response and parasites.
IgA - in mucous membrane.
Type 1 IgE hypersensitivty reaction
- Acute Anaphylaxis
- Hayfever
- Asthma
- Immune memory to something causing an allergic response
- Atopy
Definition and examples of atopy
inherited tendency to exaggerate IgE response
e.g. hayfever, eczema, asthma
What are Type 1 reactions driven by?
Histamine; mast cell mediators which release cytokines and tryptase
Which test can show is someone is having an IgE/anaphylaxis reaction
Tryptase test
Different types of reactions within type 1
Local e.g. wheezing
Systemic e.g. anaphylaxis
Diagnosis of Type 1
Skin prick test
Radioallergosorbent test RAST
ImmunoCAP
Type 1 treatment
Prevent exposure
Anti-histamines
Steroids - reducing local inflammation
Desensitisation
Type 2 hypersensitivty reactions
IgG reaction; Ig bound to cell surface antigens
- Transfusion reactions
- Autoimmune disease
Examples of Type 2 hypersensitivity reactions (Goodpasture’s syndrome)
Goodpasture’s syndrome
- follow viral infection
- pulmonary haemorrhage in lung and glomeurulonephritis (renal inflammation of glomeruli)
Treatment: remove antibodies using steroids, cyclophosphamide, plasma exchange
Examples of Type 2 hypersensitivity reactions (Mycoplasma pneumonia)
Mycoplasma pneumonia
- cross reacting immune epitopes; protein on mycoplasma looks like protein on haemoglobin
= Antibodies react with antigen on red blood cells causing agglutination and haemolytic anaemia.
Type 3 hypersensitivity reactions
immune complex disease, activation of complement-IG bound to antigen
Lumps of antibody + target get deposited in the skin, lung, kidneys ect + activate immunity -> tissue damage
(do not get cleared away )
example: farmer’s lung, SLE, Post-streptococcal GN
Type 4 hypersensitivity
T-cell mediated delayed type hypersensitivity
Examples:
- Tuberculosis
- contact dermatitis
- Formation of granulomas of T cells and macrophages (Slow) keeping inflammation away from other tissue.
- Dependent upon activation of T cells
- Widespread granulomas and inflammation affect many organs (lung, eyes, skin, nervous system)
Hypersensitivity drug induced reactions (examples)
Injury, hypersensitivity, haptenization
Breathlessness, cough, fever, chest pain
Respiratory failure
Types of drugs: Amiodarone - lung fibrosis Bleomycin - direct pneumotoxicity Methotrexate NSAIDs
Pathophysiology - cycle
- Respiratory tract infection due to microbial insults/defect in host defence
- Bronchial inflammation
- Respiratory tract damage -> progressive lung disease
Normal vs abnormal CFTR protein
Normal: transports protein on membrane of epithelial cells and moves Cl- ions out of cells
Abnormal: lead to disregulated epithelial fluid transport; does not move Cl- ions out causing mucus to build up outside of cell
Cystic Fibrosis diagnosis
- genetic profile (heel prick test at birth)
- Clinical symptoms (frequent infection, malabsorption, failure to thrive)
- Abnormal salt/Cl- exchange; raised skin salt
- Late diagnosed vs infertility services
Cystic fibrosis symptoms (Respiratory)
- Persistent cough with thick mucus
- Wheezing
- SOB
- Frequent chest infections
- Sinusitis, nasal polyps
Cystic fibrosis symptoms (Digestive)
Bowel disturbances
Weight loss
Obstruction
Constipation
Cystic fiborsis complications
Sinusitis and nasal polyps
Airway obstruction, bronchiectasis, pneumothorax, haemoptysis
Obstructive billiary tract disease
Enzyme insufficiency leading to diabetes
Distal intestinal obstruction syndrome, rectal prolapse
Infertility
CF Treatment
Rescue antibiotics - IV antibiotics
CF Prevention management: Segregation Surveillance - review every 3 months Airway clearance - physio + exercise (remove mucus) Nutrition Psychosocial support
Drugs:
Suppression of chronic infections - antibiotic nebs
Bronchodilation - salbutamol nebs
Anti inflammatory - azithromycin, steroids
Diabetes - insulin
Vaccinations - influenza, pneumococcal
Personalised medicine:
Individual tailored target medicine
Stratified based on predicted response or risk of disease
Genetic information major factor
Allows each patient to benefit from treatment
What does AATD stand for? What is it?
Alpha-1 antitrypsin deficiency
Autosomal recessive genetic disorder with 80 different mutations of the SERPINEA1 gene on C14 chromosome.
Consequences of AATD
Early onset emphysema/bronchiectasis because of unopposed action of neutrophil elastase in lung due to not enough alpha-1 antitrypsin.
Normal blood gas ranges for PaO2, PaCO2 and pH
PaO2 - 10.5-13.5kPa
PaCO2 - 4.5-6.0kPa
pH - 7.36-7.44
Altitude blood gases
PaO 2 - 7 kPa
PaCO 2 - 3 kPa
pH - 7.44
Determinants of PaCO2
PaCO2 directly proportional to 1/alveolar ventilation
PaCO2 = k V’CO2/V’A
Alveolar gas equation
PAO2 = PiO2 - PaCO2/R*
PiO2 = pressure of inspired O2 R = respiratory quotient A = Alveolar a = arterial
Calculating PaO2
- PiGas = Patm x Fi Gas
- PAO 2 = PiO 2 - PaCO 2 / R
- PaO 2 = PAO 2 - (A-aDO 2 )
Why are alveolar and arterial oxygen pp not equal?
Not all of the oxygen enters the blood from the alveoli
Normal response of lungs at altitude? (6)
Hypoxia leads to hyperventilation, which allows for better oxygen absorption at altitude. CO2 levels drop leading to a smaller difference between alveolar and arterial oxygen.
More oxygen is retained.
Minute ventilation is increased, leading to a lowered PaCO2.
Alkalosis intitially
Tachycardia.
What compensates for alkalosis caused by high altitude?
Renal bicarbonate excretion
What is Boyle’s law?
At constant temperature, the absolute pressure of a fixed mass of gas is inversely proportional to its volume.
P1V1 = P2V2
What is Henry’s Law? What is the significance to do w lungs and depth
The amount of gas dissolved in a liquid is directly proprtional to the partial pressure of the gas.
As a result, more gas dissolves into tissues at DEPTH. If ascending rate exceeds the body’s capacity to clear this excess gas; inert bubbles form in the tissues -> decompression illness.
What is Dalton’s Law? What is its significance?
Individual gas pressures add up to total air pressure.
PO2 increases as you descend.
Due to this law, O2/N2 toxicity can occur.
What is ATA? How much is 1 ATA?
atmosphere absolute
1ATA = 100kPa
Every 10m you descend, ATA increases by +1
Pulmonary oxygen toxicity (ATA)
PiO2 > 0.5 ATA
What is inert gas narcosis?
Nitrogen toxicity. N2 is forced into tissue, lung and brain. It worsens with increased pressure. Influencing factory include cold, anxiety, fatigue and drugs.
What is decompression illness?
Delayed ‘dived’ symptoms.
N2 in body tissues and moves into CNS and brain.
Type I - cutaneous
Type II - neurologic
What is an arterial gas embolism (AGE)
If an inexperienced diver takes a deep breath in gas expands rapidly, causing chest to expand and pulmonary veins rip. Air moves to the head and gas enters circulation via torn pulmonary veins.AGE can cause death.
Pulmonary barotrauma
Air leaks into chest Air leaks from burst alveoli: - pneumothorax - pneumomediastinum - subcutaneous emphysema
Asthma
Common chronic inflammatory disease
Characterised by variable and recurring symptoms, reversible airflow obstruction and bronchospasm.
Common symptoms include wheezing, coughing, tight chest and shortness of breath.
Environmental influences (asthma)
- Pollens, fungi, pets, air pollution
- Infectious agents and micro-organisms
- Aero allergen exposure occurs after birth
- Pets
- Air pollution (aggravating lung disease; response to pollutants can be analogous to vieal respones). Air pollution can aggravate pre-existing lung diseases such as COPD.
What is hypersensitivity pneumonitis?
Inflammation of the alveoli caused by hypersensitivity to inhaled dusts. Lungs become inflamed.
Immune complex related disease, where an antigen reacts with an antibody, causing a mornal IgG response.
Different forms of hypersensitivity pneumonitis?
Acute
Sub acute
Chronic
Influences causing hypersensitivity pneumonitis?
Farmers lung
Bird fanciers lung
Metal working gluids
Characteristics of COPD
Chronically poor airflow
Worsens over time
Slow progressive lung disease
FEV1/FVC ratio of COPD
FEV1:FVC < 0.7
Breathing is autonomic. What does this mean?
It is a non-conscious effort. The rate and depth of breathing depends upon cyclical excitation and control of muscles in the upper and lower airway, diaphragm and chest wall.
Overnight breathing
Hypopneic (slow breathing)
6 breaths a minute
Which neurons form the respiratory control centre?
groups of neurons in the PONS and MEDULLA
Respiratory control centre neurons send impulses to the primary respiratory muscles via which 2 nerves?
phrenic
intercostal
Which respiratory group controls expiration
ventral
Which respiratory group controls inspiration
dorsal
Which respiratory group controls the rate and pattern of breathing
pontine
Where are peripheral chemoreceptors found?
Carotid body
Aortic body
What do peripheral chemoreceptors detect large changes in?
pO2
When low levels of oxygen are detected, what happens?
Afferent impulses travel via the glossopharyngeal and vagus nerves to the medulla oblongata and the pons in the brainstem.
Which actions then happen to increase the pO2
The respiratory rate and tidal volume are increased to allow more oxygen to enter the lungs and subsequetly diffuse into the blood. Blood flow is directed towards the kidneys and the brain (as these organs are the most sensitive to hypoxia). Cardiac output is increased in order to maintain blood flow, and therefore oxygen supply to the body’s tissues.
Where are central chemoreceptors?
Central chemoreceptors are located in the medulla oblongata of the brainstem.
What do central chemoreceptors detect?
They detect changes in the arterial partial pressure of carbon dioxide.
When changes are detected, what happens?
central chemo
The receptors send impulses to the respiratory centres in the brainstem that initiate changes in ventilation to restore normal pCO2.
What does the body do restore CO2 levels.
Detection of an increase in pCO2 leads to an increase in ventilation. More CO2 is exhaled so the pCO2 decreases and returns to normal. Detection of a decrease in pCO2 leads to a decrease in ventilation.
What ratio establishes the pH of the CSF
pCO2: [HCO3-]
Which levels remain relatively constant and which change?
HCO3- levels remain relatively constant whereas CO2 freely diffuses across the blood-brain barrier.
What constitutes the blood-brain barrier?
arterial blood supply and the cerebrospinal fluid
When CO2 reacts with H2O what does it produce? What effect does this have on the pH?
Carbonic acid
Lowers the pH
Does a small decrease in pCO2 lead to an increase or decrease in the pH of the CSF?
Increase in the pH, and vice versa is there is a small increase in pCO2, which decreases the pH.
When the pH of the CSF changes, what are the respiratory centres stimulated to do for either an increase or decrease?
Increase in pH = decrease ventilation
Decrease in pH = increase ventilation
What happens if pCO2 levels stay abnormal for a longer period of time? Which disease is this relevant in?
Choroid plexus cells within the blood brain barrier allow HCO3- ions to enter the CSF. Movement of HCO3- ions alters the pH which in turn resets the pCO2 to a different value.
COPD
Centres in the pons and their function
Pneumotaxic centre: reduces respiration rate
Apneustic centre: moderates effect of pneumotaxic centre i.e. moderating amount of lung stretch. Prevents over inflation of lungs.
What does the pons moderate?
natural breathing patterns
Groups in the medulla oblongata? When is each one active?
Dorsal Respiratory Group - predominantly active during inspiration.
Ventral (front) respiratory group - active during both inspiration and expiration.
What do both groups have in common?
Each are bilateral and project into the bulbo-spinal motor neurone pools and interconnect
What is the medulla oblongata in charge of?
Phasic discharge of action potentials
What is the Central Pattern Generator?
Neural network of interneurons.
Where is the CPG located?
Located with in the dorsal and ventral respiratory groups
CPG function
generate repetitive patterns of motor behaviour independent of any sensory input or feedback.
Inspiration (nerves)
Progressive increase in inspiratory muscle activation. DRG + VRG both involved. Lungs fill at a constant rate until the tidal volume is reached. At the end of inspiration, there is a rapid decrease in excitation of the respiratory muscles due to the medulla and pons.
Expiration (nerves)
First part of expiration; active slowing with some inspiratory muscle activity (breaking between late expieration and early inspiration). Increased demand leads to further muscle activity being recruited. Can become active with additional abdominal wall muscle activity.
Afferents of carotid and aortic bodies individually
Carotid = glossopharyngeal nerve Aortic = vagal
Neurotransmitter secretion of peripheral chemoreceptors
When exposed to hypoxia, type I cells release stored neurotransmitters that stimulate the cuplike endings of the carotid sinus nerve. Neurotransmitter secretion during hypoxia sends afference to DRG/VRG Pons to increase ventilation.
3 Lung receptors
Stretch
J
Irritant
Afferent nerves of lung receptors
Vagus nerve
Stretch receptors: location, function and speed
In smooth muscle of conducting airways.
They sense lung volume.
Slow adapting and rapid adapting.
Irritant receptors: location, function and speed
Larynx and pharynx and larger conducting airways.
Receptors for inhaled particles.
Rapidly acting: cough, gasp
J (juxtapulmonary capillary) receptors
Pulmonary + bronchial C fibres
What is the definition of hypoxia?
a deficiency of oxygen at tissue level
What is the most common type of hypoxia?
Hypoxic hypoxia
Hypoxemia - in which the arterial partial pressure of O2 is reduced
What are the most common causes of hypoxia?
- Hypoventilation
- Diffusion impairment
- Shunting
- Ventilation/Perfusion mismatch
What does hypoventilation result in and why does it happen?
Hypoventilation results in an increased arterial partial CO2 pressure. This is because the alveoli fail to ventilate adequately.
Causes:
- muscular weakness (motor neurone disease)
- obesity
- loss of respiratory drive (E.g. if you prevent the brain from accessing the lungs due to morphine for example)
What does diffusion impairment result from? What is it caused by?
Results from thickening of the alveolar membranes or a decrease in their surface area which causes the partial pressure of O2 to decrease and alveolar partial pressure to fail to equilibrate.
Caused by pulmonary oedema, anaemia and interstitial fibrosis between alveoli and capillaries.
What is shunting? Where can it occur?
anatomical abnormality of the cardiovascular system that causes mixed venous blood to bypass ventilated alveoli in passing from the right side of the heart to the left side. This can occur when there is a ventricular septal defect.
It can also be a result of an intrapulmonary defect in which mixed venous blood perfuses unventilated alveoli. This can occur in bronchial arteries.
What is ventilation-perfusion mismatch? What can it be caused by?
Occurs in COPD and many other lung diseases where arterial partial CO2 pressure may be normal or increased, depending on how much ventilation is reflexively stimulated.
Causes:
- pulmonary embolus (blockage of artery in the lung)
- asthma
- pneumonia
- pulmonary oedema
What is hypercapnia
Carbon dioxide retention and an increased arterial partial pressure of CO2.
What is hypercapnia caused by?
hypoventilation (main)
or V/Q mismatch
Oxygen, CO2 and HCO3- in Type 1 respiratory failure
low pO2
low or normal pCO2
normal HCO3-
What are the causes of type 1 respiratory failure? Which is the most common?
pulmonary embolism = most common COPD pneumonia asthma pulmonary oedema high altitude
Oxygen, CO2 and HCO3- in Type 2 respiratory failure?
low pO2
high pCO2
normal HCO3- **
What are causes of type 2 respiratory failure?
hypoventilation opiate overdose severe asthma COPD hypothyroidism muscle disorders drowning
What is different when type 2 is chronic?
high HCO3- because the kidneys make more to buffer the increase in H+
When does type 1 resp failure progress to type 2?
when patient becomes fatigued and respiratory rate decreases, no longer blowing off CO2
Why can you not give high flow O2 to COPD patients?
As their central chemoreceptors will have reset to accommodate increase PaCO2 - oxygen will then cause further reduction as peripheral chemoreceptors are inhibited by increased O2, leading to death from acidosis caused by hypercapnia.
Anaemic hypoxia
not enough Hb to carry O2
Stagnant hypoxia
blood flow to the tissue is too slow
Histotoxic hypoxia
toxic agents prevents cell from using O2
