Respiratory System Flashcards
Internal respiration
Also called cellular respiration
The utilization of oxygen in the metabolism of organic molecules
External respiration
Exchange of oxygen and CO2 between an organism and the external environment
Functions of the Resp System
Provide O2
Eliminate CO2
Form speech sounds (phonation)
Defend against microbes (host defence)
Trap and dissolve blood clots arising from systemic (usually leg) veins
Modulate concentration of biologically active molecules
What type of epithelium is respiratory epithelium?
Pseudostratified ciliated columnar epithelium
Respiratory epithelium
Pseudostratified ciliated columnar epithelium
Rests on thick basement membrane
Several cell types (columnar, basal, etc)
Ciliated columnar cells are most abundant
Goblet cells and intraepithelial lymphocytes and dendritic cells are also present
Lamina propria is well vascularized
Upper airway
Nose to vocal cords
Humidifies and warms inspired air
Nasal turbinates
Increase surface area in the nose
Superior, middle and inferior ones
Project into the nasal passages from the side wall of the inside of the nose
Olfactory epithelium
Basal cells, supporting cells, olfactory neurons
Lies on the roof of the nose above the top turbinate
To the brain through the cribiform plate in the ethmoid bone
Pseudostratified epithelium
Dendrites of olfactory neurons have cilia with membrane receptors for odor molecules
4 paranasal sinuses and their location
Frontal: above the eyes
Maxillary: under the eyes
Ethmoid: between the eyes
Spheoidal: behind the eyes
Sinuses
Air filled spaces
Lined by ciliated epithelium
Active mucociliary clearance to clear the main nasal passages
Lighten the skull (easier to be upright), provide resonance to the voice
Which sinus has the opening at the top? What problems does this cause?
Maxillary sinus
Mucus can be retained in the sinus
Can result in infection
3 major structures of the larynx
Epiglottis
Arytenoids
Vocal cords
Arytenoids
A pair of small three-sided cartilage structures to which the vocal folds are attached
Extrinsic vs intrinsic muscles of the larynx
Ex: change larynx position in swallowing
In: alter relative position (and tension) of vocal cords in production of sound
How many lobar bronchi are there?
1 for each lobe!
2 on the left, 3 on the right
Right lung sections
Upper, middle and lower lobes
Oblique and horizontal fissue
Left lung sections
Upper and lower lobe
Oblique fissure
Functions of conducting zone
Pathway for air flow
Defends against microbes, toxic chemicals and other foreign material via mucociliary clearance
Warms and moistens air
Phonation (vocal cords)
What do bronchioles lack?
Supporting cartilage and glands
What type of epithelium is present in very small bronchioles?
Simple cuboidal cells with cilia
Terminal bronchiole composition
Only one or two layers of smooth muscle cells surrounded by connective tissue
Epithelium contains ciliated cuboidal cells and many low columnar nonciliated cells
Clara cells
Nonciliateded
Only found towards the periphery
Secrete components of surfactant
Detoxify potentially harmful compounds in the air
Produce secretory component for the transfer of IgA into lumen
Type 1 vs Type 2 epithelial cells
1: squamous for gas exchange
2: make surfactant, rounded shape
3 important parameters for efficient gas exchange in lungs
- Large driving force (partial pressure gradient)
- Large surface area
- Distance needs to be small
Respiratory distress syndrome of the newborn
Type 2 alveolar cells mature at 24 weeks
Babies born before this time do not have enough surfactant to overcome surface tension forces
We have artificial surfactant to give them
What is surfactant made of?
Mixture of phospholipids and proteins, including DPPC
DPPC molecules align themselves on alveolar surface, with hydrophobic portions attracted to each other and hydrophilic portions repelled
2 types of circulation to the lungs
- Pulmonary circulation: from right heart, for gas exchange
2. Bronchial circulation: from aorta and provides nourishment to lung tissue
Pleurisy
Inflammation of the pleura
Often caused by viral infections
Inflammed pleural layers rub against each other resulting in pain
Pleural effusion
Excess of fluid in pleural cavity
Muscles of normal inspiration
External intercostals
Diaphragm
Accessory muscles of inspiration
Sternocleidomastoid
Scalenus
Accessory muscles of expiration
Internal intercostals Abdominal muscles (main): rectus abdominus, internal and external obliques, transversus abdominis
What nerve innervated the diaphragm
Phrenic nerve
Submucosal glands
Contain both serous and mucus cells
Present whenever there is cartilage
Serous cells secrete watery fluid containing anti inflammatory and anti oxidant compounds which helps flush the mucus out of the glands
Volume of the conducting zone and alveolar region
CZ: 150 mL
AR: 2.5-3 L
3 main defence mechanisms to protect airways
- Physical: cough, barrier function, mucociliary clearance
- Chemical: mucus composition and viscosity, antimicrobial peptides
- Cellular: phagocytosis by macrophages, immune response
Carbon monoxide
Largest pollutant by weight
Produced by incomplete combustion of carbon in fuels
Binds to hemoglobin with 200x greater affinity than O2
Evidence that it impairs mental skills
Reduced by catalytic converters
Most dangerous
Colourless, tasteless, no smell
Nitrogen oxides
Produced when fossil fuels are burned at high temperatures in power stations and cars
Causes inflammation of eyes and upper resp tract during smoggy conditions
High concentrations cause acute tracheitis, acute bronchitis, and pulmonary edema
Sulphur oxides
Corrosive, poisonous gases produced when sulfur containing fuels are burned, mainly by power stations
Causes inflammation of mucus membranes, eyes, upper resp tract and bronchial mucosa
Short term exposure to high concentrations causes edema
Cigarette Smoke
Important pollutant because it is inhaled, so [ ] much higher than atmospheric pollutants
Sufficient to impair exercise and mental performance
Smoke contains nicotine, which stimulates the ANS producing tachycardia, hypertension, and sweating
Tar gives cancer
Also higher risk for chronic bronchitis, emphysema, and heart disease
Smoking causes increase in airway resistance
3 ways to clear particles
- Impaction: largest particles fail to turn at the corners of the resp tract - hits wet surface and sticks
- Sedimentation: gradual settling of particles due to their weight. Dominates in small airways
- Diffusion: random movement of particles as result of their continuous bombardment by gas molecules. Only for smallest particles
Cough
Protective reflex to remove foreign material and secretions from the airways
Integral part of host defence mechanisms against inhaled particles and noxious substances
Especially important when other methods of clearance are overwhelmed
Can be excessive in obstructive diseases
Absent at birth
Stimuli trigger specialized cough receptors, located in or under airway epithelium
Functions of tight junctions
Provide structural support
Inhibit movement of materials via paracellular space (barrier function)
Separate apical and basolateral domains (fence function)
2 sources of mucus and 2 layers in mucociliary clearance
Sources: submucosal glands and goblet cells
Layers: gel (top, sticky, more viscous) and sol (less viscous)
Mucociliary clearance
Tips of cilia interact with gel layer to propel the mucus blanket in small peripheral airways and in trachea
End point: pharynx, then swallowed
Primary Ciliary Dyskinesia
Immotile cilia syndrome
Impaired ciliary activity, so incidence of resp infection is high
Usually caused by absence of dynein arms normally found in 9 peripheral microtubular doublets
Missing radial spokes too
Motion is abnormal and not coordinated into metachronal waves
Clinically: bronchitis, rhinitis, sinusitis, otitis media, obstructive lung disease, male sterility
Cystic fibrosis
Defective ionic permeability results in defective mucociliary clearance
Results in repeated bacterial infections
Most common fatal genetic disease in caucasions
Alveolar macrophages
No mucus or cilia in alveoli so particles are engulfed by macrophages
Phagocytose and then migrate to small airways to load on MCC or leave via lymphatics
Contain lysozyme so it can directly kill bacteria
Activity is impaired by cigarette smoke, alcohol, alveolar hypoxia, ozone, radiation
Composition of mucus
Water
High molecular mass cross linked glycoproteins + serum and cellular proteins (ex: albumin, enzymes, and Igs)
DNA present in pathological conditions (from bacteria and host - increases viscosity)
Mucins
Gigantic biopolymers of glycoproteins characterised by presence of one or more large region rich in serine and threonine
Amino acids covalently attached via linkage sugar NAG
Polyanionic
Usually 70%+ carbohydrate
Provide structural framework of defense barrier, prevent barrier dehydration, present carbohydrate sites which pathogens attach to
Also contain antibacterial/viral/fungal agents
Phlegm
Purulent secretion that is a product of airway inflammation
Contains breakdown products of inflammatory and epithelial cells, including DNA and actin fragments, bacteria, cell debris, and mucins
Sputum
When phlegm is expectorated
Antimicrobial peptides
Cationic, so bind to negatively charged prokaryotic cell membranes
Then disrupt cell wall
Action is inhibited by high salt levels or serum proteins
Common bacterial pathogens in lung infections
P. aeruginosa H. influenzae K. pneumoniae Burkhoderia cepacia Staph aureus
Lysozyme
Secreted from epithelial cells and submucosal glands
Induces lysis of gram positive bacteria
Lactoferrin
Activated by inflammatory and infectious stimuli
Sequesters iron from microbes
Pneumoconiosis
Non-neoplastic reaction of the lung to inhaled mineral or organic dust
Fibrosis
Deposition of scar tissue
Non elastic
Lung becomes less compliant so its really hard to breathe in
Coal workers pneumoconiosis
Results in lesions called coal dust macules
Composed of coal laden macrophages within the walls of the respiratory bronchioles and adjacent alveoli
Often emphysema surrounding macule
Acute silicosis
Infiltration of the alveolar walls with plasma cells, lymphocytes and fibroblasts, with some collagen deposition
Alveoli fill with eosinophils
Widening of alveolar walls with collagen and clusters of type 2 cells
Nodules rare
Asbestos
Family of naturally occurring hydrous silicates found in soil
Fibers are either long and curly (serpentine) or straight and rodlike (amphibole)
Heat resistance properties (so used for insulation)
3 health hazards identified
Asbestosis
Diffuse interstitial fibrosis
Asbestos fibers deposit at branch points in the distal airways and alveolar ducts, resulting in an inflammatory cascade of cellular activation, recruitment, and injury
Result is a fibroblast proliferation and extracellular matrix deposition in the interstitial space
Pleural disease from asbestos
May occur after trivial exposure
Most common are pleural plaques (+/- calcification) and pleural thickening (benign)
Changes in pleura result in restrictive type in disease
Malignant mesothelioma may develop
Can develop up to 40 years later
Severe chest pain
Low survival rate
Glutathione
Anti-oxidant
Lots in the sol layer
Reactive Oxidative Species examples
Superoxide anion Nitric oxide Peroxynitrite Hydroxyl radical Hydrogen peroxide
Oxidant stress results in…
Peroxidation of membrane lipids Depletion of nucleotides Rises in intracellular Ca2+ Cytoskeletal disruptions DNA damage Changes in ion channel functioning
Oxidant stress in asthma
More inflammatory cells, and they produce more ROS
Astham attacks are associated with immediate formation of O2-
ROS production by neutrophils correlates with severity of airway hyperresponsiveness
Increased biomarkers of eosinophil activation include release of granule proteins such as EPO and MBP
Superoxide dismutase
Breaks down superoxide radical into H2O2
Obstructive Airway disease and 4 examples
There is an obstruction to airflow leading to increased resistance
Can be in the lumen, in the airway wall, or surrounding the airway
Ex: chronic bronchitis, asthma, emphysema, cystic fibrosis
Restrictive Airway disease and an example
Expansion of the lung is restricted
Can be from alterations in the parenchyma, diseases of the pleura/chest wall/neuromuscular apparatus
Ex: Acute respiratory distress syndrome
Asthma
Characterised by increased responsiveness of the airways to various stimuli Widespread bronchoconstriction Excessive mucus secretion Smooth muscle hypertrophy Chronic inflammation Chest tightening, wheezing and coughing Increasing prevalence
Status asthmaticus
When the medications for asthma stop working
Can no longer relieve bronchoconstriction
Airway hyper-responsiveness definition
The capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in a comparable degree of airway narrowing in health subjects
Methacholine challenge
Given to patient via nebulised spray, and causes bronchoconstriction via muscarinic receptors
Degree of narrowing quantified by spirometry
Asthmatics will react to much lower doses
Bronchodilator administered to assess the degree of reversibility
Airway remodelling in asthma
Structural changes in the epithelium including:
Airway wall thickening, epithelial hypertrophy, goblet cell metaplasia, subepithelial fibrosis, smooth muscle hyperplasia and hypertrophy
Most common treatment for asthma
Short acting beta agonists counteract bronchoconstriction (Ventolin)
Chronic obstructive pulmonary disease
Progressive loss of lung function with airflow obstruction that is not fully reversible with bronchodilators
Airflow obstruction is the result of pulmonary inflammation associated with bronchitis and mucus hypersecretion together with emphysema
Emphysema
The presence of permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls
Destruction of the gas exchange surfaces
Destruction of alveolar walls resulting in enlargement of the air spaces distal to the terminal bronchiole, small airways narrowed and reduced in number
Smoking/air pollution causes, also a1 anti-trypsin deficiency
Centriacinar emphysema
The destruction is limited to the central part of the lobule and the peripheral ducts and alveoli may be fine
Most often found at apex of upper lobe, but spreads downwards as disease progresses
Panacinar emphysema
Distension and destruction of entire lobule
Throughout lung, but more common towards bottom
More effect on lung function (much worse than centriacinar)
Alpha-1 Antitrypsin
A major inhibitor of serine proteases, including neutrophil elastase
Genetic disease
Homozygotes (especially smokers) are likely to develop COPD at an early age
Alpha antitrypsin protein accumulates in the ER of the liver
Sever panacinar emphysema can develop, beginning in lower lobes, by age 40
Chronic bronchitis
Chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of productive chronic cough have been excluded
Excessive mucus production due to hypertrophy of mucus glands in large bronchi
Chronic inflammation in small airways, cellular infiltration and edema
Caused by smoking
Cystic fibrosis
Caused by loss of function mutations in the gene encoding CFTR protein
Deficient epithelial anion (Cl-) permeability
Multiple organs affected
Lung disease currently accounts for most of the morbidity and mortality
CF effects on
- Airways
- Sweat glands
- Pancreas
- Small intestine
- Mucopurulent material, mucus plugging of smaller airways
- Decreased reabsorption of NaCl by water. Impermeable ductal epithelial cells leads to elevated sweat Cl-
- ~95% of patients have some dysfunction. Enzyme insufficieny = malabsorption of fat and protein
- Meconium becomes thickened and congested in ileus (results in blockage)
Symptoms of CF
Persistent cough with productive thick mucus
Wheezing and shortness of breath
Frequent chest infections, which may include pneumonia
Bowel disturbances, such as intestinal obstruction or frequent, oily stools
Weight loss or failure to gain weight despite increased appetite
Salty sweat
Infertility in men and decreased fertility in women
Class2 CFTR mutations
Trafficking defect
CFTR doesn’t go to surface, so it gets retained and degraded in Golgi
Mutation in delta F508
Missense mutations and in-frame deletions
2 main therapeutic strategies for CF
- CFTR potentiators: improve Cl- transport through CFTR
2. CFTR correctors: rescue the trafficking defect
Acute lung injury and acute respiratory distress syndrome
Characterized by acute inflammation that affects gas exchange
Can result from direct pulmonary injury or indirect blood borne insults
Breathlessness and pulmonary edema
Cathelicidins
Only human example is LL-37, 37 amino acids
Similar broad-spectrum activity to defensins, both Gram positive and gram-negative bacteria, plus Candida albicans
Induced by pathogens such as P aeruginosa
Over-expression in mice results in increased protection against bacterial challenge
Chemotactic for neutrophils, monocytes, mast cells and T cells
