Respiratory System

• the epithelium
• mostly what's described

• includes structures that carry air to & from sites of gas exchange while warming, moistening, & cleansing it
• no gas exchange takes place IN the conducting portion because the walls of the structures are too thick

nasal cavity → nasopharynx → larynx → trachea → (intrapulmonary) bronchi → bronchioles → terminal bronchioles

• the epithelium that covers the surfaces of the conducting portion of the respiratory tract
• it's a pseudostratified, ciliated, columnar epithelium with goblet cells
• very deep in the lung this epithelium will no longer be ciliated

where gas exchange takes place, specifically in the thin-walled alveoli

order: respiratory bronchioles → alveolar ducts → alveolar sac → alveoli

• type I pneumocytes
• type II pneumocytes
• alveolar macrophages

• not a huge region, comprises part of the upper lateral wall & septum of the nose
• is pseudostratified 
• has stem cells (basal cells) that sit on the basal lamina
• bipolar neurons (olfactory cells) pass through the basal lamina
• they have cilia at the top of the epithelium that's bathed in serous fluid from Bowman's glands

• bipolar neurons with modified, non-motile cilia present at knob-like endings
• receptors for odorants are present on the surface of the CILIA - such cells turn over constantly (unusual for CNS)

• odors/molecules have to dissolve in the fluid from the Bowman's glands at the surface of the epithelium
• they then bind to odorant binding proteins
• the compound then binds to receptors on the olfactory cell (bipolar neuron) cilia

• CN I (cranial nerve I)
• any cells associated with these olfactory cell axons are Schwann cells (because they're part of the peripheral nervous system)

• because they divide / turn over (@ ~the same rate as skin, olfactory epithelium)
• the capacity is diminished in Parkinson's & Alzheimer's - patient early on complain of anosmia

• olfactory epith. is quite thick (especially compared to respiratory epithelium)
• upper most nuclei belong to the sustentacular (supportive) cells
• nuclei right along the basement membrane = basal cells
• all other nuclei in the middle belong to the bipolar neurons
• can see nerve bundles with the nuclei of associated Schwann cells
• everything else below = Bowman's glands

• can see pseudostratified, columnar epithelial cells
• can see the cilia at the top
• dark line under cilia = basal bodies; anchor them & organelles from which they develop
• also see goblet cells
• no respiration takes place where there is respiratory epithelium (too thick for gas exchange)

it isn't present on villi

• goblet cells visualized in respiratory epithelium
• goblet cells don't have cilia b/c they open up & exocytose their contents (mucus granules

• made lots of products, eg. NTs like catecholamine, serotonin, hormones like calcitonin
• are part of the DNES (diffuse neuroendocrine system)
• can't be observed using H&E

• muco-cilliary 'escalator' doesn't work well
• CFTR is located ~ where the basal bodies are (found at the apical end of ciliated cells, not goblet cells)
• when CFTR doesn't properly transport Cl-, Cl- can't exit the cell, meaning Na+ stays in the cell to maintain electroneutrality, & WATER also goes into the cell FROM the mucus
• this dehydrates the mucus making it THICK
• thick mucus is hard for cilia to move, so pathogens that'd normally be cleared won't be

• this portion of conducting pathway isn't covered by respiratory epithelium
• - larynx contains stratified squamous epithelium (SSNKE)
• contains vocal chords & vocalis muscle that controls the vocal chords
• several cartilages (most hyaline, a few elastic) anchor the vocalis muscle

• directs food away from the airway during swallowing
• has non-keratinized stratified epithelium on its superior surface and has respiratory epithelium on its inferior surface
• lamina propria contains some seromucous glands + an elastic cartilage plate

• consists of:
• vestibular folds (false vocal cords) - respiratory epith.
• true vocal cords - stratified squamous epith, control phonation
• each true vocal cord has a large elastic fiber bundle, vocal ligament, & a parallel SKELETAL muscle bundle, the vocalis muscle

long tube extending from the larynx down to the point where it bifurcates into the 2 main-stem bronchi

• sits anterior to the esophagus
• lined by Respiratory (Conducting) Epithelium [pseudostratified ciliated columnar w/ goblet cells]
• Lamina Propria is the next layer after epithelium; it contains elastic fibers
• there is NO muscularis mucosa proximal to the lamina propria in the trachea
• instead there's Adventitia with Hyaline Cartilage that's C-shaped
• Trachealis Muscle connects the 2 ends of the C-shaped Hyaline Cartilage Adventitia
• 

1. to contract when you cough & generate a lot of intrathoracic pressure that causes the trachea to expand (this muscle prevents over-expansion)

2. it allows the esophagus to expand into the trachea when you're swallowing something

it gets transformed into bone tissue

• Mucosa (innermost layer, closest to lumen):
• - covered by respiratory epithelium
• - has a PROMINENT basement membrane
• - & underlying lamina propria

• Submucosa:
• - contains MANY mixed seromucous glands
• - is separated from mucosa by a layer of elastic fibers

*there is no muscularis mucosa separating the mucosa & submucosa in the trachea

• they're not - they're histologically identical to the trachea
• can identify changes once you get into the lung proper

• the RIGHT one
• because the right primary bronchus is wider, shorter & more VERTICAL than the left, & it makes a smaller angle with the axis of the trachea than the left (more room for things to enter)

• Intra-anything means it's actually in the substance of the lungs
• everything before/outside of the lungs = extra pulmonary (trachea + main bronchi)

• cartilage in the intra-pulmonary areas won't be C-shaped like it was extra-pulmonarily
• instead it'll exist as 'plates' in the aventitia

• cartilaginous airways that arise from subdivisions of the primary bronchi via branching
• intrapulmonary bronchi themselves divide to give rise to lobar & segmental bronchi
• as bronchial diameter ↓ → thickness & complexity of the wall ↓

• prominent muscularis mucosa (folds - also characteristic of bronchioles & larger bronchi due to preparation)
• hyaline cartilage plates
• 
• *anytime you see hyaline cartilage in the adventitia in any level, the passageway is an intrapulmonary bronchus
• (once the plates disappear the passageway is called a bronchiole)

• the thick smooth muscle of intrapulmonary bronchi
• histamine release from mast cells due to an allergic reaction causes constriction of the smooth muscle layer, narrowing the passageway

• a passageway is by definition a bronchiole if it lacks hyaline cartilage in its adventitia
• 
• still too thick for gas exchange
• are typically 1mm or less
• has no glands in the submucosa, lacks cartilage altogether 
• contains only a few goblet cells
• epithelium is no longer really pseudostratified, mostly cuboidal at this point; most nuclei lie basally & a clear apical cytoplasm can be seen
• a muscularis mucosa is present

• non-ciliated, dome-shaped apex, with the ultrastructure of a protein secreting cell
• 1. make surfactant so bronchioles don't collapse in on themselves
• 2. act as progenitor stem cells of the bronchiole epithelium during regeneration & repair
• 3. protect against inflammation & oxidative stress

proteins - such as CC16 - can be measured & if present in serum are indicative of epithelial damage in the lung

• you know a bronchiole is terminal because the region downstream has out-pouchings known as alveoli
• you can't differentiate a terminal from standard bronchiole via cross-section only 
• is the smallest, last portion of the conducting pathway
• the epithelium contains Club cells & some cuboidal ciliated cells (to remove any mucous which might move this far)
• muscular layer is made up of an incomplete circular layer of smooth muscle
• each terminal bronchiole divides into 2 or more respiratory bronchioles
• 

• Respiratory Bronchiole
• once you get passed the terminal bronchiole you can have regions with thin walls (alveoli, where gas exchange occurs) & thick walls (conducting)
• 

• make up the first part of the respiratory portion
• has a cuboidal epithelium (with ciliated cells, goblet cells & clara/club cells) is similar to that of a terminal bronchiole BUT the wall is interrupted by alveoli
• 
• can see smooth muscle (conducting) & out-pocketing (alveoli that contain capillaries in their walls for gas exchange)

• alveoli increase in number
• goblet cells disappear
• frequency of ciliated cells decreases

• lies downstream of respiratory bronchioles
• entire wall is composed of alveoli out-pocketings (thin not thick wall with no smooth muscle)
• ANY place along the duct is thin enough to have gas exchange
• 

• where the alveolar ducts end
• multiple alveoli wrapped in elastic fibers

• surfactant, which reduces the surface tension of surface membranes 
• surfactant is amphipathic: made up of lipids [dipalmitoylphosphatidylcholine, DPPC] & proteins [surfactant protein A - D]
• it also makes lungs more compliant

type II pneumocyte

• non-functional lungs is a big problem for premature infants because surfactant production starts at 6 months in the fetus
• RDS may occur in premature babies that have insufficient surfactant
• can treat with corticosteroids to ↑ surfactant or just give exogenous surfactant

type I pneumocyte: stretch a lot; gas exchange takes place over them

type II pneumocyte: cover a smaller SA than type I; usually found in alveoli corners

Macrophages (Dust cells)

• in the middle of alveolar cell walls (septa)
• the barrier for gas exchange is between capillary endothelium & type I pneumocytes
• gas must traverse both cells + their shared basement membrane for exchange

• take up inhaled molecules via pinocytosis
• can then be transported through to capillary endothelial cells & subsequently transported through the blood
• 

chunkier, have microvilli extending out



contain lamellar bodies* in cytoplasm that contain surfactant (are lipid rich)



histologically type II cells/lamellar bodies look like little clearings

• type II can divide
• type I cannot
• renewal of type I pneumocytes requires proliferation of type II cells

• small pores that may interrupt alveolar septum & connect one alveolus to another
• they equalize pressure & allow collateral air flow
• are important when small airways are blocked
• can also play a role in the spread of infection from one alveolus to another

• Veins bring blood back to the heart (usually deoxygenated)
• Arteries pump blood away from the heart (usually oxygenated)

1. Pulmonary Arteries: carry deoxygenated blood from the heart/pulmonary trunk; run with conducting airways (share adventitia); are a thin walled low pressure/resistance system that end as capillary networks (for gas exchange)

2. Pulmonary Veins: carry oxygenated blood back to the heart; usually run by themselves in the substance of the lung, aren't connected to the conducting airway (separated by a sea of alveoli)

• the bronchiole tree
• 

• pulmonary veins
• carrying oxygenated blood in isolation (sea of alveoli) back to the heart

Bronchial Arteries & Veins

• arteries are small, branch directly off the aorta & supply the bronchiole tree itself
• 
• have no function in gas exchange, just supply the lung organ