Respiratory System Flashcards
What is the difference between external and internal respiration?
External: O2 and CO2 exchange between lungs and atmosphere, alveoli and blood, blood transport, and between blood and cells
Internal: O2 utilization by mitochondria to regenerate ATP and form CO2
What are the primary functions of the respiratory system?
- Respiration
- Homeostatic regulation of body pH
- Defence against microbes
- Modifies arterial concentration of chemical messengers
- Vocalization
- Sense of smell
What is the pleural sac?
double layered serous membrane that surrounds the heart. includes inner visceral pleura and outer parietal pleura with thin layer of fluid to hold the layers together and lubricate them.
What is the difference between the inner visceral pleura and the outer parietal pleura?
visceral: attached to lung by connective tissue
parietal: attatched to thoracic wall and diaphragm
How many generations of branches are there in the respiratory tract?
around 23 generations of branches, each one narrower, thinner and shorter than the last. Divided into conducting zone and respiratory zone.
What is the conducting zone?
Area of 150mL anatomical dead space where gases are warmed, humidified and transported down pressure gradients. (generation 1-16)
What is the bronchial wall made of?
Smooth muscle, elastic tissue and cartilage and lined by mucus-secreting, ciliated epithelium
What is the respiratory zone?
Area of respiratory tract that holds the post inspiration volume (3,000 mL) where gases move internally by bulk flow and diffusion. (generation 16-alveoli)
What is the structure of the respiratory zone?
Huge, thin surface area for gas exchange richly supplied with capillaries. Lacks cartilage and smooth muscle to allow less hindrance to diffusion, but has elastin fibers.
Why are macrophages in the respiratory zone?
Foreign matter entering the respiratory zone is engulfed and destroyed.
What are the pores of Kohn?
Small openings in the walls of the alveoli in the lungs. They are filled with fluid and connect adjacent alveoli to allow accessibility for exchange
What are alveoli shaped like?
- Polyhedral in shape, 0.25mm diameter.
- Composed of a single layer of flat type 1 cells and interspersed with cuboidal type II cells.
- Connected by elastin fibres
- Attached to capillaries via basement membrane.
What is the difference between type I and type II alveolar cells?
Type I: squamous, where most gas exchange occurs, on top of basement membrane
Type II: secrete surfactant upon stretching (deep breathing), reabsorb Na+ and H2O
What is tidal volume?
volume of air that moves in and out of lungs per breath (500-4,600 mL)
what is inspiratory reserve volume?
maximal air volume that can be inspired FOLLOWING normal inspiration (3,000 mL)
what is expiratory reserve volume?
maximal amount of air that can be expired following a normal expiration (1,000 mL)
What is residual volume?
volume of air in the lungs following a maciximal expiration (1,200 mL)
What is vital capacity?
Maximal volume of air that can be exchanged per breath. Inspiratory reserve - expiratory reserve. (4,600 mL)
What is the difference between minute ventilation and alveolar ventilation?
Minute: volume of air inhaled/exhaled per minute = tidal volume x respiratory rate
Alveolar: volume of air that enters the alveoli per minute = (tidal volume - dead space) x respiratory rate
What is atmospheric pressure?
Pressure of the outside air (760mmHg at sea level)
What is intra-alveolar pressure (Palv)
Pressure within the alveoli (-1 to +1 mmHg at rest)
What is the relationship between Patm and Palv? How does it affect inspiration/expiration volume?
Palv > Patm: expiration
Palv < Patm: inhalation
Insp/exp volume = Patm-Palv / bronchiolar resistance
What is intrapleural pressure?
Pressure within the pleural sacs (-4 to -7 mmHg) that is ALWAYS negative (pulling in rather than pushing) and ALWAYS less than Palv
What is transpulmonary pressure?
Pressure gradient between alveoli and intrapleural sac (Palv-Pip)
What expands the thoracic cavity?
Release of ACh at neuromuscular junctions of the diaphragm and external intercostal muscles
what is the difference between passive and active expiration?
Passive: elastic recoil of lungs and thoracic cage return ribs and diaphragm to original position
Active: contraction of intercostals and abdominal muscles forces air out
What are the steps to inspiration?
- contraction of diaphragm and external intercostals
- chest wall expands
- decreased intrapleural pressure
- Increased transpulmonary pressure (Palv-Pip)
- Decreased Palv
- Increased Patm - Palv
- Air flows into alveoli until Palv = Patm
What are factors affecting pulmonary ventilation?
- lung compliance
- airway resistance
What is lung compliance and how is it calculated?
how easily the lungs expand when exposed to a change in pressure, dependent on stretchability and surface tension within alveoli
CL = ∆ lung volume / ∆Tp
What is fibrotic lung disease and what does it result in?
Chronic inhalation of fine particulate matter deep into the lungs. Results in inflammatory process that builds collagen in lung tissue that. decreases lung compliance, impairing inspiration, and slow diffusive gas exchange.
How does the surface tension at the air-water interface within the alveoli affect lung compliance?
Attractive forces between H2O molecules resist alveolar expansion, increasing work for inspiration. This is avoided with amphipathic phospholipid surfactant that decreases cohesive forces on the alveolar surface, increasing lung compliance.
What is newborn respiratory distress syndrome?
Deficiency of surfactants in premature infants causes lung compliance to decrease, which is treated with artificial ventilation and aerosol administration of artificial surfactant.
What are the passive forces that change airway resistance in a single breath?
Transpulmonary pressure and lateral traction
How does Tp affect airway resistance?
during inhalation, Pi increases, and thus Tp increases, which increases airway radius and decreases resistance.
How does lateral traction affect airway resistance?
small airways are physically connected to surrounding alveolar tissue by elastic connective tissue fibers, so when alveolar sacs expand outward, they pull the small airways more open, decreasing resistance.
What affects bronchial smooth muscle tone?
- Parasympathetic stimulation: release of ACh causes bronchioconstriction
- Paracrine agents: mast-cell histamine release causes contraction of bronchiolar smooth muscle and stimulates mucus secretion
- CO2: high PCO2 = dilation, low PCO2 causes constriction
How does asthma affect airway resistance?
bronchioconstriction and inflammation due to hyper-responsiveness of smooth muscle to irritants
How does emphysema affect airway resistance?
Elastin in lung tissue is degraded, reducing elastic recoil, which causes collapse of alveoli and small airways. Lung compliance increases but impairs expiration by trapping air in lungs. (high residual volume)
How to calculate partial pressure?
Partial pressure = fraction of gas x total pressure
What are the directions O2 and CO2 flow when following partial pressure gradients in the alveoli and pulmonary vein?
O2: 105 mmHg in alveoli > 40 mmHg in pulmonary vein = O2 moves INTO vein
CO2: 40 mmHg in alveoli < 46 mmHg in pulmonary vein = CO2 moves OUT of vein
How is the coupling of ventilation with perfusion regulated?
Increased PCO2: bronchiodilation, pulmonary arteriole constriction, systemic arteriole dilation
Increased PO2: bronchioconstriction, pulmonary arteriole dilation, systemic arteriole constriction
What is hemoglobin’s structure?
Respiratory pigment found INSIDE red blood cells composed of two alpha globin and two beta globin protein chains. Each is bound to a Fe2+ containing heme group for O2 binidng.
What is myoglobin?
Monomeric respiratory pigment that facilitates O2 delivery within skeletal and cardiac muscle
What are the two conformational states of hemoglobin?
Oxyhemoglobin (HbO2): closed/relaxed/high affinity state
Deoxyhemoglobin (dHb): open/tense/low affinity state
Why are relaxed and tense states high and low affinity?
Tense: allosteric effector binding creates salt bridges (H+) that stabilize the protein’s tense state and keep the O2 binding sites shut.
Relaxed: Effector release breaks salt bridges, causing the protein state to relax, revealing the O2 binding sites.
What is cooperative oxygen binding?
Four subunits of hemoglobin are connected in a way that the conformational change in one subunit is rapidly transferred to the other three subunits.
Why is the plateau portion of the oxygen equilibrium curve important?
Spans PO2 in alveoli/pulmonary capillaries; ensures that hemoglobin is >90% saturated over a wide range of PO2 values
Why is the steep portion of the oxygen equilibrium curve important?
Spans PO2 in systemic capillaries; venous blood is saturated creating a large O2 reserve that can be tapped into during exercise
What is P50?
Plasma PO2 at which 50% of hemoglobin molecules are saturated with oxygen (50% T, 50% R state)
What does a low and high P50 mean?
Low: it takes less PO2 for hemoglobin to be saturated (high affinity for O2)
High: it takes more PO2 for hemoglobin to be saturated (low affinity for O2)
What are the allosteric effectors of hemoglobin and how do they work?
H2, DPG, CO2, inorganic ions bind to hemoglobin to stabilize the T-state and increases P50. This shifts OEC to the right, allowing offloading of O2 by lowering affinity.
What is the bohr effect?
surface exposed histidine residues and N terminus of four globin chains can reversibly bind to protons from acidification of CO2. This creates positive charges that form salt bridges with anionic residues, stabilizing T state, increasing blood P50, and decreasing O2 affinity.
Why is the Bohr effect important?
The harder a tissue works (producing more CO2 and H+), the more O2 gets released.
How does DPG act as an allosteric effector?
DPG can form up to five bonds with cationic residues of beta chains (B1Val, B2His, B82Lys, B143His) which strongly stabilizes the T-state, decreases oxygen affinity to promote oxygen offloading.
How does pulmonary disease and anemia affect DPG production?
Chronically undersaturated arterial blood increases DPG production, increasing blood P50 above 28mmHg. This allows more O2 to be extracted from Hb at systemic capillaries with relatively little effect on O2 uptake in the lungs.
How does carbon dioxide act as an allosteric effector?
Carbon dioxide binds to amino group of the 1st residue of each alpha and beta chain, forming a carbamino protein (NHCOO-) which forms salt bridges with cationic residues which stabilizes the T state, unless dominated by DPG.
How do chloride ions act as allosteric effectors?
As pH declines and Hb cavity becomes progressively more cationic, chloride ions can cross bridge certain cationic residues (cation-Cl-cation) and stabilize the T state.
How does temperature affect blood affinity?
Increasing temperature increases free energy that can be used to weaken the Hb-O2 bonds, lower O2 affinity and promote offloading of O2, especially during exercise.
How does exercise affect cardiovascular adjustments and hemoglobin?
CV: increased cardiac output and capillary recruitment at exercising muscles
Hemoglobin:
- increased temp lowers blood affinity
- increased PCO2 and [H+] decrease blood pH and increase bohr effect
- decreased pH creates more binding sites for DPG and Cl-
How does nitric oxide aid O2 delivery?
Hemoglobin facilitates endocrine transport of nitric oxide. When RBC senses low PO2 at working tissues, Hb releases NO to vasodilate the vessel and increase blood flow to allow for more opportunity to offload and deliver oxygen.
How are mitochondrial oxidases in RBCs protected?
oxygenated myoglobin and hemoglobin lower [NO] by converting it to nitrate.
How is fetal hemoglobin different than adult hemoglobin?
Fetal hemoglobin uses gamma globin chains instead of beta, which have 4 out of 8 adult DPG sites uncharged, so only 3 bonds can be made, lowering P50, increasing affinity for O2.
Why is carbon monoxide dangerous?
CO binds to heme groups with 200x higher affinity than O2, lowering blood O2 content at any given PO2, and resisting release.
What are the three forms CO2 takes in the blood?
- dissolved in blood plasma (5-10% during exercise)
- Bound to amino groups of plasma proteins (less than 1% in normal proteins, 5% in hemoglobin)
- Bicarbonate ions catalyzed by carbonic anhydrase (90%)
What is the path of venous CO2 and O2 transport at TISSUES?
- CO2 from tissues enters the RBC via concentration gradient
- CO2 + H2O are turned to HCO3- by carbonic anhydrase
- HCO3- gets transported back to blood in exchange for one Cl- ion, via band 3 antiport exchanger protein
- Cl- is given to oxyhemoglobin (HbO2), assisting DPG in stabilizing T state, offloading oxygen which follow concentration gradient into tissues.
What regulates breathing?
- emotions and voluntary control: send signals to cerebral cortex which sends signals to medulla
- chemoreceptors: peripheral and central, signal to medulla
- muscle and joint receptors: sense exercise, signals to medulla
- pulmonary stretch receptors: senses overinflation of lungs and signals to medulla
How do peripheral chemoreceptors work?
Glomus cells of carotid and aortic bodies are strongly activated when plasma PO2 drops below 60mmHg. They release neurotransmitters onto sensory neurons projecting to the medulla, primarily increasing RATE of ventilation.
How do central chemoreceptors work?
- High CO2 in capillaries cross blood brain barrier and enter cerebrospinal fluid.
- CO2 is converted into bicarbonate and a proton.
- Bicarbonate stays in the CSF, but the protons cross the blood brain barrier and enter the medulla interstitial fluid.
- H+ trigger sensory neurons of the medulla, increasing the depth of ventilation.
