Respiratory Flashcards
Nasal vestibule
Area just inside the nostril leading to nasal cavity
Defence to particulates in the vestibule
Hairs that catch large particulates
Turbinates of the nose
Outpouching of bone associated with epithelium in the vestibules of the nose to increase SA of nasal cavity to air condition
The paranasal sinuses and their role
Small hollow spaces in the bones around the nose
Frontal (lower forehead)
Maxillary (cheekbones)
Ethmoid (beside the upper nose)
Sphenoid (behind the nose)
All of which are paired
They’re evaginations of mucous membrane from the nasal cavity
They humidify air and resonate sound
Frontal sinuses
Within the frontal bone and the pair is separated by a midline septum
Found above orbit and across superciliary arch (where the eyebrows are found)
Nerve Supply of Frontal Sinuses
Ophthalmic division of V nerve (trigeminal nerve)
Maxillary Sinuses
Located within body of the maxilla
Pyramidal shape
Lateral wall of the nose is it’s base and it’s apex is the zygomatic process of the maxilla
Floor-alveolar process
Roof - floor of orbit
Maxillary sinuses open into the …. via the …
Open into the middle meatus
Via the hiatus semilunaris
Ethmoid Sinuses
Aero like appearance (labyrinthine structure)
Between the eyes
Ethmoid sinuses drain by the … into the …
Semilunar hiatus
Middle Meatus
What are meatuses of the nasal cavity?
Spaces created by the turbinates
What is the nerve supply of the Ethmoid Sinuses?
Ophthalmic and maxillary divisions of the V (trigeminal) nerve
Sphenoid Sinuses
Inferior to pituitary fossa and optic canal
Medial to cavernous sinus
Sphenoid sinuses empty into the…
Sphenoethmoidal recess
Nerve supply of sphenoid sinuses
ophthalmic divisions of the V (trigeminal) nerve
Eustachian tube
Connects middle ear to nasopharynx aerating middle ear system by clearing mucus into the nasopharynx
Folds of oropharynx
Palatoglossal then palatopharyngeal arches (on superior wall and into lateral walls)
Palatine tonsils on lateral walls
Larynx valvular function
Prevents liquid and food entering the lung
Single laryngeal cartilages
Epiglottis x1
Thyroid x1
Cricoid x1
Double laryngeal cartilages
Cuneiform x2
Corniculate x2
Arytenoid x2
Palpable slit in larynx is called…
The Cricothyroid Ligament
Access to trachea below level of blockage that doesn’t require you to go through bone (in an emergency)
Larynx innervation
By 2 branches of the Vagus Nerve:
Superior Laryngeal Nerve: Divides into internal branch which supplies sensation, and external branch which provides motor supply to cricothyroid muscle
Recurrent Laryngeal Nerve:
Provides motor supply to all muscles except the cricothyroid muscle (there is a R and L RLN)
Course of the Left RLN
Lateral to arch of aorta, loops under aorta, ascends between oesophagus and trachea
Approximate minute ventilation (air going in and out of lungs per minute)
5 litres
Carina
Bifurcation of the the trachea at the Sternal angle
What joins the incomplete C-ring cartilage of the trachea?
Trachealis muscle
What lines the internal trachea surface?
Ciliated, columnar, pseudostratified epithelium (goblet cells present)
Sensory Innervation of Trachea
Recurrent Laryngeal Nerve
Arterial Supply of Trachea
Inferior Thyroid Artery
Venous Drainage of Trachea
Brachiocephalic, accessory hemiazygos veins and azygos vein
Position of heart towards left of chest has what effect at the bifurcation point of the L and R main bronchus?
The R main bronchus is more vertically disposed, the L is more bent
Length of R and L main bronchi
R - 1-2.5cm (related to pulmonary artery)
L - 5cm (related to aortic arch)
Main Bronchi Bifurcate into…
Lobal Bronchi (3 for R lung: Upper, Middle, Lower and 2 for L: Upper (and lingula the remnant of middle), Lower)
Segmental bronchi divide into…
Terminal bronchioles into respiratory bronchioles
Acinus
Distal to terminal bronchiole comprising alveolar ducts, alveolar sacs and alveoli
Alveoli connected by pores of Kohn
Pleura
2 main layers of mesodermal origin
Parietal (has pain sensation) - attached to chest wall
Visceral (only has autonomic sensation)- attached to lung
Why is inflammation a “double-edged sword”?
It’s our defence against infection BUT many of us die of diseases caused by inflammatory processes
How is inflammation initiated?
In the tissues by epithelial production of H2O2 and release of cellular contents (provides stimulus for production of cytokines which recruit inflammatory cells)
How is inflammation amplified?
Tissue resident macrophages (alveolar macrophages in lungs) which coordinate what’s coming into the lung with rest of immune system (prevent large influx of neutrophils)
Toll-like (TLRs) and Nod-like (NLRs) receptors role and difference (innate response)
They’re signalling receptors in immune response
Toll-like receptors found on membrane (recognise common molecular patterns in pathogens)
Nod-like are found in cell cytoplasm
Endocytic/Phagocytic receptors (innate response)
Recognise common things on bacteria and engage in phagocytosis
PAMPs and DAMPs
Pathogen-associated molecular patterns
Damage-associated molecular patterns
Establishment of alveolar macrophages in the lung
Initial wave of foetal macrophages which are replaced by circulating foetal monocytes which colonise the lung and become tissue-resident alveolar macrophages (once exhausted by fighting infection, they are removed from lung and replaced by new monocyte-derived alveolar macrophages)
Macrophage plasticity
Macrophages can change behaviour to suit environment
During inflammation - host defence phenotype (activate immune system)
Post inflammation - Tissue-repair phenotype
Proportions of neutrophil location
Half free flowing in blood
Half adhere to endothelium in lungs and rest of body
What happens to neutrophils during resolution of inflammation? (after pathogen has been cleared)
They apoptose and are engulfed by macrophages and removed
Things receptors on neutrophils can recognise
-Bacterial structures
(cell walls, lipids,
peptides)
-Host mediators
(cytokines)
-Host opsonins
-Host adhesion
molecules (allow them
to stick to vessel walls)
Activation of neutrophils
By signalling transduction pathways (so neutrophils know the scale of the threat)
Adhesion of neutrophils to endothelium
Margination (initial contact by receptors called selectins on endothelium and neutrophils which interact)
Adhesion (firm adhesion and flattening of the neutrophil by receptors called integrins)
Neutrophils then migrate across endothelium into tissues
Neutrophil phagocytosis
Membrane pinching and invagination forming a phagosome
Which fuses with granules forming a phagolysosome
NAPDH Oxidase
An enzyme complex that exists on the membrane of a phagosome in a neutrophil which generates a ROS (toxic to bacteria)
Neutrophil apoptosis (post-inflammation)
Neutrophil advertises that it’s apoptopic using cell surface molecules which is recognised and engulfed by macrophages (changes macrophage role from attack to restoration of normal tissue function)
Nasopharynx lined by…
Pseudostratified columnar epithelium with goblet cells (respiratory epithelium)
Inferior portion of pharynx lined by…
Stratified squamous epithelium
Trachea lined by…
Pseudostratified columnar epithelium with goblet cells (respiratory epithelium)
Epithelium goes from … to … in the finer bronchioles and then down to … in the alveoli
Columnar -> Cuboidal -> Squamous
Molecules in epithelium of respiratory tract that are secreted to play a role in passive host defence
Antiproteases
Anti-fungal peptides
Anti-microbial peptides
Antiviral proteins
Opsins
AT1 cells vs AT2 cells
AT1 - cover >95% of alveolar surface and are essential for air-blood barrier function of lungs
AT2 - Produce host defence proteins to protect alveolar space
(AT2 cells can also differentiate into AT1 cells)
Mucus in respiratory tract
Produced by goblet cells and submucosal glands
Contain water, carbohydrates, lipids and proteins
Removes foreign material and reduces fluid loss (reduces evaporation across respiratory epithelium)
Mucociliary Escalator
Rhythmic beating of ciliated cells in respiratory epithelium moving mucus from the lower respiratory tract into the pharynx
Cough as a non-immune defence
Expulsive reflux protecting lungs from foreign bodies (involuntary or voluntary) (irritation in lower respiratory tract)
Sneeze as a non-immune defence
Involuntary expulsion of air (irritation in upper respiratory tract)
Following injury to airway apithelium…
Basal cell layer is a stem/progenitor cell pool that can migrate to the surface that proliferate and redifferentiate
Mucus plugs
Prevent airflow through airways
What innervates the diaphragm?
C3, C4, C5 (phrenic nerve)
Sensory afferents leave via Vagus (X) nerve
Dead space in ventilation
Volume of air not contributing to ventilation
Anatomical - 150mls
Alveolar - 25mls
(175mls total)
So breathing in 500mls, only 350mls enters alveoli
Bronchial Circulation
Arteries arise from descending Aorta
Bronchial veins drain into SVC
Systemic Pressure - 120mm/80mm
Pulmonary Circulation
L and R Pulmonary Arteries
Lower pressure - 24mm/10mm
Broncho-vascular bundle
Pulmonary artery and bronchus run alongside each other (artery not running alongside a vein)
Normal PaCO2
4-6kPa
Alveolar Gas Equation
PAO2 = PaO2 - PaCO2/R
Normal pH of arterial blood
7.4 (7.36-7.44)
Carbonic acid / bicarbonate buffers to control pH
CO2 + H2O <-(carbonic anhydrase)-> H2CO3 + H+ + HCO3-
CO2 under respiratory control (rapid)
HCO3- under renal control (less rapid)
Response to respiratory acidosis
Often caused by reduced alveolar ventilation (CO2 build up)
This is corrected by reducing CO2 back down again or increasing HCO3-
Respiratory acidosis (hypoventilation)
Increased PaCO2, decreased pH, mild increased HCO3-
Respiratory alkalosis (hyperventilation)
Decreased PaCO2, increased pH, mild decreased HCO3-
Metabolic acidosis
Reduced HCO3- and decreased pH
Metabolic alkalosis
Increased HCO3- and increased pH
FEV1
Forced Expiratory Volume in 1 second (normal if above 80% of predicted value)
FVC
Forced Vital Capacity (normal if above 80% of predicted value)
PEF
Peak Expiratory Flow (rate)
Single measure of the highest flow during expiration (very effort dependent) (measured using peak flow meter)
Measuring lung volume by gas dilution
Measures air in lungs + all communicating airways
Gas breathed in from box
Change in conc once the gas is returned to box is a result of the distribution relative to the volume of the airways
(areas of lungs blocked by cysts etc. can’t be considered)
Airways restriction if…
FVC is below 80% of predicted value
Airways obstruction if…
FEV1/FVC is <0.70
Alveolar ventilation is inversely proportional to…
PaCO2 (low alveolar ventilation = build up of CO2)
Locations of centre in brain that control basic breathing rhythm
Pons - pneumotaxic centre and apneustic centre
Medulla - dorsal respiratory group (DRG) and ventral respiratory group (VRG)
Difference between DRG and VRG
DRG - primarily inspiration focused
VRG - primarily expiration focused
Expiration muscle activity
1st part - passive elastic recoil of thoracic wall + some contraction of inspiration muscle to slow down expiration
2nd part - Expiration muscle contraction
Central chemoreceptors sensitive to CO2
Located in brainstem and pontomedullary junction but not the DRG/VRG complex
They’re sensitive to PaCO2 perfusing the brain
PaCO2 diffuses into the CSF shifting equation to make more H+ which binds to a chemoreceptor increasing the stimulus to breathe
Why do central chemoreceptors go off PaCO2 and not [H+]?
The blood brain barrier is impermeable to H+ and HCO3- (at cerebral capillaries)
Peripheral Chemoreceptors (responsible for all response to hypoxia due to reduced PaO2 but also respond partly to PaCO2) location and afferents
Carotid bodies - at bifurcation of common carotid, IX cranial nerve afferents
Aortic bodies - ascending aorta, vagus (X) nerve afferents
(fire in response to hypoxia to increase PAO2)
Response to PaCO2 comes from…
60% central chemoreceptors
40% peripheral chemoreceptors
Pulmonary CO
4.5-8L/min
2 differences between pulmonary and systemic arteries
Thicker walls in systemic
More significant muscularization in systemic
Pressure in a vessel =
CO x Resistance
Pressure in pulmonary circulation =
mPAP - PAWP (pulmonary arterial pressure, left atrial pressure)
(= CO x PVR)
V/Q mismatch explained
Due to gravity, perfusion is greater in the lower parts of the lung resulting in a lower V/Q ratio resulting in lower oxygen saturation of Hb (ventilation is the limiting factor so could be caused by other things like pulmonary oedema)
Measuring exhaled nitric oxide (eNO)
Simple machines that measure nitric oxide in exhaled breathe
Measured in ppb
Normal = <25ppb
High (>50ppb) = eosinophilic airways inflammation (so could potentially indicate asthma)
Cystic fibrosis inheritance
1:25 are carriers so 1:2500 births have CF
What does the CFTR protein channel do?
Transport protein on membrane of epithelial cells that transport Cl- in and out (mutation = disregulated epithelial fluid transport)
80% of cases - Lung and GI
15% - just lung
1 atmosphere of pressure is equivalent to…
1 bar - 1000 millibars
760 mmHg / torr
10m sea water
101.3 kPa
Boyle’s Law
At constant temperature, absolute pressure of a fixed mass of gas is inversely proportional to its volume
P1V1 = P2V2
Dalton’s Law
Total exerted by a mixture of gases is equal to the sum of the pressures that would be exerted by each of the gases if it alone occupied the total volume
PiGas =
Patm x FiGas
PAO2 =
PiO2 - PaCO2/R
Death zone for breathing
Above 8000m it’s difficult to sustain life without supplemental O2
R = Respiratory Quotient =
Normally 0.8 (drops closer to 0.7 with a fat rich diet)
Pressure at top of everest (8848m)
33.5kPa
Approximate alveolar oxygen pressure difference
1kPa higher in alveoli
Normal blood pH
7.36-7.44
Normal PaCO2
4.5-6kPa
Normal PaO2
10.5-13.5kPa
Normal response to hypoxia
Increased ventilation
CO2 drops (alkalosis)
Tachycardia
In response to falling, PaO2, peripheral chemoreceptors…
Fire (carotid and aortic bodies) activating increased ventilation reducing PaCO2
4 stages of lung development
Embryonic (0-5 weeks)
Pseudoglandular (5-17 weeks)
Cannalicular (16-25 weeks)
Alveolar (25 weeks - term)
Embryonic stage of lung development
Lungs derived from foregut
They’re an outpouching of the oesophagus
Pseudoglandular stage of lung development
Angiogenesis
Mucous glands form
Lungs full of fluid at this point
Pseudoglandular stage of lung development
Angiogenesis
Mucous glands form
Lungs full of fluid at this point
Cannalicular stage of lung development
Vascularisation (formation of capillary bed)
Respiratory bronchioles, alveolar ducts, terminal sacs
Alveolar stage of lung development
Type 1 and 2 pneumocytes
Alveolar sacs
Changes in alveoli from birth to 3-5 years
Thinning alveolar membrane and interstitium (increased alveolar complexity)
Systemic vessels vasoconstrictors and vasodilators
Vasoconstrictor - O2
Vasodilator - hypoxia/acidosis/CO2
Pulmonary vessels vasoconstrictors and vasodilators
Vasoconstrictors - hypoxia/acidosis/CO2
Vasodilator - O2
Physiology of foetal circulation
Shunting of blood from R->L
High pulmonary vascular resistance (hypoxia)
Low systemic resistance (placenta)
What occurs in alveoli of a foetus?
Foetal airways distended with fluid through active pumping in
Role of ductus venosus
Shunt allowing oxygenated blood in umbilical vein to bypass the liver to the IVC (as blood is oxygenated in placenta)
Shunts about 30% of umbilical blood directly to IVC
Shunts of blood in foetus heart
Ductus arteriosus (between pulmonary trunk and arch of aorta)
Foramen ovale (between the 2 atria)
Fate of ductus arteriosus after birth
Muscular wall contracts to close after birth (mediated by bradykinin) becoming ligamentum arteriosum
Adaptive changes of circulation at birth
Fluid squeezed out of lungs through birth process (tight gap)
Adrenaline stress = increased surfactant release
Gas is inhaled = O2 vasodilates pulmonary arteries, pulmonary vascular resistance falls, RA pressure falls = closed foramen ovale
Umbilical arteries constrict
Ductus arteriosus constricts
Change in pressures pre and post birth
Pre birth - Pulmonary artery (pulmonary) higher
Post birth - Aorta (systemic) higher
Laplace’s Law
P = 2T / r
Surfactant is…
A phospholipid formed by type 2 pneumocytes
Abolishes surface tension
Dramatic increase 2 weeks before birth (so premature babies are deficient)
Regulation of airways tone (diameter) controlled by…
ANS - Contractile signals cause increased intracellular Ca in smooth muscle activating actin-myosin contraction
Smooth muscle can tighten up due to inflammation
Parasmypathetic bronchoconstriction
Vagus nerve neurons terminate in parasympathetic ganglia in airway cell
Short post-synaptic nerve fibres reach muscle releasing ACh which acts on muscarinic receptors (M3) on muscle cells
Stimulates airway smooth muscle contraction
Sympathetic bronchodilation
Nerve fibres release noradrenaline activating alpha/beta adrenergic receptors
Activation of beta2 receptors on airway smooth muscle causes muscle relaxation
Phagocytes vs Lymphocytes
Phagocytes - (monocytes and neutrophils) phagocytose
Lymphocytes - make and release antibodies and kill diseased cells
Antibodies
Produced by B-lymphocytes (plasma cells)
Neutralise/elimijate pathogens
