1. Capacities+Volumes
1.1. FEV1/FVC
1.1.1. Describes lung function
1.1.2. Lower FEV1[obstructive
1.1.3. Normal or heightened ration= restrictive
1.2. Alveolar Venilation
1.3. Resistance/Compliance
1.3.1. Inversely related
1.3.2. Increase in resistance leads to a decrease in airflow
1.3.2.1. Upper/larger airways set up in parallel (1/R) to decreased resistance
2. Smooth Muscle
2.1. Sympathetic=Gs
2.1.1. Bronchodilation
2.2. Parasympathetic=Gq
2.2.1. Contraction
2.2.1.1. MLCKII->cAMP
3. Diseases/Pathologies
3.1. Obstructive Lung Diseases
3.1.1. Decreased FEV1
3.1.2. Asthma
3.1.3. Cystic fibrosis
3.1.4. Chronic OBstructive Lung Disease (COPD)
3.1.4.1. hyperdevelopment of trapezius, scalenus, and sternomastoid
3.2. Restrictive Lung Diseases
3.2.1. Normal or increased ratio
3.2.2. Pulmonary fibrosis
3.2.3. COVID
3.2.3.1. Silent/happy hypoxia
3.3. Obstructive Sleep Apnea
3.3.1. apnea=periods of ceased breathing
3.3.2. Increased pressure difference in the trachea
3.4. Bronchopulmonary Displasia
4. Anatomy
4.1. Lungs are kept expanded by negative pressure of about -4mmHg
4.1.1. pleural fluid(surfactant)
4.1.1.1. increased amount of surfactant of larger alveoli and decreased surfactant in smaller alveoli
4.1.1.1.1. allows pressure of larger alveoli to equalize with high pressure of smaller alveoli
4.1.1.1.2. a phospholipid that reduces H bonding
4.1.1.2. Decrease in work needed for inspiration
4.1.1.2.1. Decrease in surface tension+decrease in elastic recoil
4.1.2. integrity of pleural cavity
4.2. Important pressures
4.2.1. Atmospheric pressure (PB)
4.2.2. P(alviolar) for equalizing
4.2.3. IntraPULMONARY pressure
4.2.3.1. that determines flow (PB-P(alv)=±1)
4.2.4. IntraPLEURAL
4.2.4.1. keeps lungs from collapsing
4.2.4.2. less negative at top than bottom
4.2.4.2.1. more expansion at base of lung than apex
4.2.4.2.2. better ventilarion at base
4.2.4.2.3. more perfusion
4.3. Air flow
4.3.1. Tidal volume highest during the transition from insp. to exp.
4.3.2. Inspiration
4.3.2.1. decreased thoracic(intrapleural) volume
4.3.2.2. decreased lung(intrapulmonary) pressure
4.3.2.3. Post-inspiratory refracrtory period limits respiration rate
4.3.2.3.1. amplitude of inspiratory excitiation does not increase rate
4.3.3. Expiration
4.3.3.1. decreased thoracic(intrapleural) volume
4.3.3.2. increased lung(intrapulmonary) pressure
4.3.3.3. Forced expiration limited by dynamic airway compression
4.3.3.3.1. peak of expiratory flow is effort dependent
4.4. Positioning
5. Medulla
5.1. Central Pattern Recognition- Medulla and Pons
5.1.1. mechanical input from lung stretch receptors- Sensors
5.1.2. Recieve input from central and peripheral chemoreceptors- Sensors
5.1.3. Pontine Respiratory Group (PRG)/Kölliker-Fuse(KF) region
5.1.3.1. For transition between inspiration and expiration *fine-tuning
5.1.3.1.1. Pneumotaxic Center=promotes rate of expiration and depth of inhilation
5.1.3.1.2. Apneustic Center=stimulation of DRG to inspire
5.1.3.1.3. pneumotaxic and apneustic center communicate through reciprocal inhibition
5.1.3.2. located in the pons
5.1.4. Ventral Respiratory Group (VRG)
5.1.4.1. Expiratory neurons in Rostral and Caudal areas
5.1.4.2. Inspiratory neurons in intermediate area
5.1.4.2.1. These project to Pre-Bötz premotors
5.1.4.3. Contains premotor neurons
5.1.5. Dorsar Respiratory Group (DRG)
5.1.5.1. Contains Inspiratory neurons
5.1.5.2. Processes sensory input from peripheral chemoreceptors, stretch receptors...
5.1.5.3. projects to PRG, VRG, and respiratory motor neurons
5.1.5.4. Phrenic Nerve Activity(PNA) of the diaphragm sychronized with inferior cardiac nerves (ICN and NTS)
5.1.5.4.1. sympathetic correlations between respiratory motor input and cardiac chemo/baro rece[tion
5.1.6. Dorsolatereral Pons is reached by RTN through glutamate signaling
5.1.6.1. Motor response
5.1.7. Pre-Bötzinger Complex/Parafacial respiratory group (pFRG)
5.1.7.1. inspiratory pacemaker neurons that generates rhythm
5.1.7.1.1. rhythm generated by recurrent excitiation (burstlet hypothesis)
5.1.7.2. non-pacemaker cells generate shape and control phases
5.1.7.3. mediates active expiration
5.1.7.4. Amplification of burst activity
5.1.7.4.1. Persistent Na+ current for subthrushold input
5.1.7.4.2. Ca++-activated nonspecific cation current to modulate neuronal input
5.1.8. Postinspiratory complex (PiCo)
5.1.8.1. regulate postinspiratory activity
5.1.8.2. neurons here contribute to arrhythmias
5.2. Central Chemical Regulation(pH)
5.2.1. Retrotrapezoid Nucleus(RTN)
5.2.1.1. TASK-2
5.2.1.1.1. Deletion=decrease in pH sensitivitity
5.2.1.1.2. TWIK-related Acid-Sensitive K+ channels
5.2.1.1.3. inhibition
5.2.1.2. TREK proteins
5.2.1.2.1. TWIK-RElated K+ Channels
5.2.1.2.2. activation
5.2.1.2.3. inhibition
5.2.1.2.4. are the downstream target of hypoxia-activated AMPK in glomus cells
5.2.1.3. KCNQ2
5.2.1.3.1. Serotonin, Ach, NE
5.2.1.3.2. known to limit excitability of chemosensitive neurons
5.2.1.3.3. activation of channels=decrease rate
5.2.1.3.4. inhibition of channels=increase rate
5.2.1.4. Phox2b
5.2.1.4.1. mutations disrupt chemical drive to breath
5.2.1.4.2. GPR4(guanine coupled)for CO2 response
5.2.1.4.3. exposure to CO2 increases cFos expression which normally regulates inflammation
5.2.1.5. P2Y2
5.2.1.5.1. P2Y1 neurons effect breathing through changes in cardiovasculature (arterioles)
5.2.1.5.2. increased expression in smooth muscle
5.2.1.5.3. regulate H+/CO2 vascular reactivity in RTN
5.2.1.6. pH sensitive K+ currents
5.2.1.7. Intrinsically H+/CO2 sensitive
5.2.1.8. project to all levels of resp circuits.
5.2.1.8.1. inhibition decreasing breathing under normal condition (not hypoxic)
5.2.2. Pre-Bòtzinger Complex
5.2.3. Astrocytes
5.2.3.1. effect central pattern control by communicating between neurons through Connexon 26 (cx26)
5.2.3.2. ATP chomosensing between glia and RTN
5.2.3.2.1. H+/CO2 evoked ATP release
5.2.3.2.2. Use of Kir4.1-5.1
5.2.3.2.3. Catecholaminergic/glutamatergic neurons regulate astrocytes
5.2.3.3. P2-R
5.2.3.3.1. when blocked eliminates pH sensing
5.2.3.3.2. Photosensitive
5.2.3.4. glial fibrillary acidic protein (GFAP)
5.2.3.5. MeCP2
5.2.3.5.1. its dysfunction involved in both Retts and breathing patterns
5.2.4. Ventral medullary surface
5.2.4.1. responsive to low pH from increase CO2 and temperature
5.3. Peripheral Chemosensing in the Carotid arteries
5.3.1. responds to low O2
5.3.1.1. leads to neural depression
5.3.2. baroreceptors more responsive to hypoxia if high H+/CO2 in arteries
5.3.2.1. glomus cells in carotid bodies
5.3.2.1.1. active at resting Vm
5.3.2.1.2. voltage independent of IO2
5.3.2.1.3. Ba+ sensitive
5.3.2.2. CN IX
5.3.2.3. CN X
5.3.2.3.1. activation of baroreceptros increase vagal drive to heart
5.3.3. EFFECTS ARE "HYPER"-ADDITIVE
5.3.3.1. independent of H+/CO2 sensing
5.3.3.2. Lead to TREK modulation
5.3.3.3. required use of AMP-activated Protein Kinase (AMPK) to inhibit K+ channels (TREK/TASK)
5.3.4. activation of sympathetic activity
5.3.4.1. control hypertension
5.3.4.2. coupled with protective hypoxia-induced potentiation of breathing
6. PaO2 v. PaCO2 sensing
6.1. Ventilation/Perfusion(V/Q)
6.1.1. Pulmonary Capillaries
6.1.1.1. Angiotensin Converting Enzyme(ACE) is responsivle for regulating blood pressure (volume control
6.1.2. Pressures influencing perfusion
6.1.2.1. P(Alv)
6.1.2.2. P(arteriol)
6.1.2.2.1. Apex
6.1.2.2.2. Middle
6.1.2.2.3. Base
6.1.2.3. P(venuous)
6.1.3. assesses how well V dot and Q dot are matched
6.1.3.1. ratio decreases from apex to base of lung because of increasing blood flow as you go to the bottom of the lung
6.1.3.2. at V/Q=1, gravity and hydrostatic pressure are main factors
6.2. PaO2=vascular control
6.2.1. Control of IK(ir) in vessels
6.2.1.1. Decreased pressure(Hypoxia)= inhibition of channels= increased depolarization
6.2.1.1.1. (hypoxic) Vasoconstriction in lungs
6.2.1.1.2. disruption of oxidative phosphorylation
6.2.1.1.3. Increased production of reactive oxygen species (ROS)
6.2.1.1.4. systemic vasodilation
6.2.1.2. Increased pressure= stimulation of channels= decreased depolarization
6.2.1.2.1. Vasoconstriction
6.2.2. small difference between PO2 and PCO2(maintained by hemoglobin) so their passive diffusions are dependent on surface area and thickness of membranes
6.3. PaCO2=bronchial control
6.3.1. Control of ventilation
6.3.1.1. Increased PaCO2(Hypercapnia)-
6.3.1.1.1. Bronchiodilation
6.3.1.1.2. Systemic vasodilation
6.3.1.2. Decreased PaCO2
6.3.1.2.1. Bronchoconstriction
6.3.2. CO2 is 24x more soluble than O2=better for signalling
6.4. Oxygen-Hemoglobin Dissociation Curve
6.5. Pulmonary Dead space
6.5.1. Anatomical= volume of conducting airways (not including alveoli) ~150mL
6.5.2. Functional/Physiological= all parts of conducting airwways that do not participate in gas exchange
6.5.2.1. volume can increase in deseased states
6.6. Gas trasnfer
6.6.1. Perfusion limitation=limitation by solubility of gas in blood
6.6.2. Diffusion limitation=limitation by solubility of gas through membranes