Normal physiology Flashcards
TLC = RV + ____
VC
TLC = FRC + ____ + _____
Vt + IRV = IC
Main inspiratory muscles appart from diaphragm
Intercostals:
- External intercostals
- Parasternal intercostals
Accessory muscles:
- Scalenes
- Sternocleidomastoids
- Trapezius
Expiratory muscles during exercise
Abnominal muscles
- Rectus abdominis
- Transverse abdominis
- Internal /external obliques
Thoracic muscles
- Internal intercostals
- Innermost intercostals
4 Methods for measurement of lung volume
- Spirometry
- Gas dilution
- Plethysmography (body box)
- Radiographic techniques
Flow-volume curve axes
X axis = volume
Y axis = flow (liters /second)
It is the derivative of the volume-time curve .
Gas dilution equation used
C1V1 = C2V2
Where:
C1 = concentration of He before dilution
V1 = volume of He before dilution
C2 = concentration of He after diluation
V2 = V1 + (what we’re looking for)
Is plethysmography more accurate than He dilution?
Yes.
Mechanism of plethysmography
Breathe out at FRC, then shutter closes. Patient breathes in against the closed shutter, leading to a change in pressure and volume in the thorax, which is calculated by a pressure transducer.
3 determinants of lung volume
- Pulmonary compliance
- Chest wall compliance
- Respiratory muscles
Transpulmonary pressure equation
Pressure at the airway opening - pressure in the pleural space
Transpulmonary pressure is used as a measure of the _______ of the lungs and airways.
Elastic recoil
What device do we use to find out the pleural pressure?
Esophageal balloon
What is the compliance difference between inspiration and expiration called, and what is it due to?
Is pressure required higher or lower during inspiration?
Hysteresis.
It is due to the lungs being more difficult to open during inspiration because of the coat of surfactant. Compliance is lower for inspiration than for expiration.
3 determinants of lung compliance
- Tissue forces (lung)
- Surface tension
- Chest wall
Does emphysema increase or reduce the forces related to the elastin-collagen-proteoglycan network of lung tissue?
REDUCE (increased compliance)
What is pulmonary surfactant?
Small layer of phospholipids in the alveoli which decreases surface tension.
Does pressure in an alveoli increase or decrease with size of alveoli?
It decreases with a larger alveoli (inversely proportional).
Does fibrosis increase or reduce compliance?
Reduce (increase forces related to the tissues).
2 vital properties of pulmonary surfactant
- Lower surface tension (increasing compliance of the lungs)
- Promote alveolar stability (reducing chances of collapse of alveoli)
Why is FRC the state of equilibrium of the pulmonary system?
Because the inward pressure of the tissue to collapse equilibrates with the outward pressure of the chest wall to expand.
What is the resting state of the chest wall?
At about 60-80% of TLC. However, in that case, the respiratory system has a tendency to collapse due to the lung tissue who has pressure inwards.
What happens at RV in terms of chest wall and elastic recoil?
Outward elastic recoil of the chest wall is stronger than the inward elastic recoil of the pulmonary tissue.
What are the determinants of RV?
- Limits of the chest wall (youth)
- Premature airway closure (older adults = loss of elastic recoil)
- Limit of expiratory force
Are lower zones of the lung more or less compliant than higher zones?
More compliant (smaller resting volumes and more easily ventilated).
In what types of airways has are we most likely to have laminar vs turbulent flow?
Laminar = peripheral airways (smaller)
Turbulent = main airways (larger)
Relationship between driving pressure and flow in turbulent flow
Driving pressure is proportional to the square of the flow.
This means that to have a same flow rate as in the laminar flow, we need more pressure.
What is the most efficient type of flow?
Laminar.
What is the name of the flow that occurs when it is perfectly laminar?
Poiseuille flow.
Relationship between driving pressure and flow in laminar flow
Directly proportional
If the flow rate in a tube is high by default, which type of flow is most likely to occur?
Turbulent flow
During laminar flow, the driving pressure needed to generate a given amount of flow varies __________ with the tube length and __________ with the _________ of the tube radius
Directly
Inversely ; fourth power
if the airway radius is halved, by how much must be the driving pressure increased to maintain the flow rate in laminar flow?
16-fold increase
Turbulent flow is most likely to occur when flow rate is _____ and tube diameter is ____.
High
Large
What does a high Reynold’s number tell us?
A higher likelihood for turbulent flow.
What is the relationship between gas density and flow type?
Higher gas density = more likelihood for turbulent flow.
What is a use of Helium related to its low gas density?
To convert turbulent flow into laminar flow in patients with upper airway obstruction.
Resistance increases or decreases with length of tube?
Increases.
True or False? Tubes connected in series have a greater total resistance than tubes connected in parallel.
TRUE!
True or False (exam question)? The dichotomous branching arrangement of the airways (tubes connected in parallel) allows for a lower total airway resistance despite the fact that the individual airways are getting smaller.
True. This is because, although each individual airway gets smaller, the total cross-sectional area of all the airways increases, reducing overall resistance.
Does lung resistance increase or decrease as we breathe in? Why?
Decrease. That is because airways are pulled open by
- Alveolar attachments on the membranous bronchioles
- Effect of negative intrathoracic pressure on the airways
How to calculate total airways resistance?
P mouth - P alveoli = Raw
Which type of resistance has the most important effect on total pulmonary resistance?
Airway resistance.
Tissue resistance has a small effect. It refers to the loss of energy as tissue molecules move past each other with changes in lung volume.
What does maximal expiratory flow depend on? (3 things)
- Airway resistance
- Elastic recoil of the lungs
- Expiratory muscle strength
What is flow limitation?
The fact that, no matter how hard we push with our muscles during expiration, the flow will remain the same past a certain point. It refers to the effort independent region of the flow-volume curve.
What is flow limitation due to?
Equal pressure points, aka choke points.
Increase in alveolar pressure is proportional to increase in pressure at the equal pressure point.
What is flow determined by, in the effort-independent portion of the flow-volume curve?
- Elastic recoil of the lungs
- Resistance of the airways
FEV1/FVC ratio in obstructive disease
Decreased (< 0.7)
FEV1/FVC ratio in restrictive disease
Same or increased
Tell me about the PEF, FEV1, FEV1/FVC, TLC and RV in emphysema (obstructive disease)
PEF = reduced
FEV1 = reduced
FVC = same
FEV1/FVC = decreased (< 0.7)
TLC = increased
RV = increased
In emphysema, there is both loss of elastic recoil and increase airway resistance because tissue is not properly hold up the airways, leading to decreased radius and increased resistance.
We see a scoop curve.
Tell me about the PEF, FEV1, FEV1/FVC, TLC and RV in fibrosis (restrictive disease)
PEF = reduced
FEV1 = reduced or same
FVC = reduced
FEV1/FVC = increased or same
TLC = decreased
RV = decreased
We see a snappy curve.
Increased elastic recoil of the lungs, but decreased compliance makes it harder to inflate them to high TLCs.
Tell me about the PEF, FEV1, FEV1/FVC, TLC and RV in chest wall disease.
PEF = reduced
FVC = reduced
TLC = decreased
RV = variable
How many times do the airways branch, from the trachea? How many of these generations are part of the conducting, and how many of the respiratory zones?
23 times.
First 16 = conducting zone
After 16th generation = respiratory zone
What is the typical tidal volume at rest vs during exercise?
500 mL
3L+ during exercise
Volume of normal anatomical dead space
150 mL
Equation for volume of fresh gas reaching the respiratory zone each minute
Va = (Vt - Vd) x f
Dead space equation
Physiological dead space = anatomical dead space + alveolar dead space
When does alveolar dead space occur?
In disease processes, when there is no blood flow to the alveoli despite good ventilation.
What is the water vapor pressure at body temperature?
47 mm Hg
What happens in terms of pH when the alveolar ventilation is too low?
Increased CO2 = increased H+ = respiratory acidosis
Do changes in HCO3- occur more rapidly or slowly than changes in CO2 levels?
More slowly.
Increased [HCO3-]impact on pH
Higher pH = metabolic alkalosis
Is the interpleural pressure more or less negative at the bottom of the lungs as compared to the apex?
Less negative. This leads to an easier expansion of the bottom of the lungs as compared to the apex.
Example of disease leading to a deformed chest wall
kyphoscoliosis
What are the two types of respiratory failure?
Type 1: Decreased PaO2
Type 2: Increased PaCO2, due to inadequate alveolar ventilation.
How many pulmonary veins are there?
4
Hyperinflation leads to inspiratory muscle dysfunction. How?
Because if the lung volume is greatly increased (emphysema), the diaphragm is flattened/shortened all the time. Muscles that are shortened do not contract efficiently.
Where do the bronchial veins drain into?
The left atrium, directly. Deoxygenated blood mixes with oxygenated blood, creating a small “shunt”.
3 functions of the bronchial circulation
- Nutrition of bronchial tree
- Maintenance of temperature and humidity of airway wall
- Provides blood elements (white cells) for inflammation and repair
True or false? The pulmonary and systemic circulations carry the same flow (cardiac output) at any one time.
True. They are in series.
Is the blood pressure higher in the systemic or in the pulmonary arteries?
In the systemic arteries.
Also, the walls are much thinner in the pulmonary arteries. They are low resistance vessels.
Resistance is the ________ _________ of flow.
Resistance is the energy cost of flow.
What is the energy cost of flow in the pulmonary vasculature?
The pulmonary vascular resistance (PVR).
In which circulation is the resistance lower?
In the pulmonary circulation.
Explain the relationship between flow, pressure and resistance in the pulmonary circulation.
For increasing of flow rates, decreasing amounts of pressures are required. This is because resistance decreases are flow rate increases. The body lowers resistance of vessels to allow increased circulation and to meet the demands of tissues.
Why is PVR lower at higher flows?
- Vascular distension
- Vascular recruitment
Alveolar vessels (septal capillaries) get (smaller or bigger) with increasing lung volumes?
Smaller.
Extra-alveolar vessels get (smaller or bigger) with increasing lung volumes?
Bigger. These vessels are held open by radial traction arising from elastic attachments to surrounding lung tissue, which expand the vessels under high alveolar volume.
Is there more blood flow at the top or at the bottom of the lung?
At the bottom. It follows gravity.
Zone 1 of the lung relationship between PA, Pa and Pv
PA >Pa> Pv.
There is little or no blood flow.
Healthy lungs have very little Zone 1.
Zone 2 of the lung relationship between PA, Pa and Pv
Pa >PA >Pv.
“Waterfall” condition.
Flow depends on the difference in pressure between the artery and the alveole.
Zone 3 of the lung relationship between PA, Pa and Pv
Pa >Pv >PA.
Flow depends on the pressure gradient between artery and vein.
What is pulmonary vasoconstriction?
Constriction of vessels in diseased regions to divert blood flow towards regions of better ventilation.
Pulmonary vessels constrict with hypoxia (low PaO2) and is accentuated by low pH.
The opposite thing happens in systemic vessels.
What substance causes pulmonary vasodilation?
Nitric oxide.
What is the net effect of hydrostatic pressure vs oncotic pressure in the capillaries?
A small gradient of pressure moves fluid out of the capillaries and into the interstitial space.
Most of this fluid is carried away by the lymphatics and a small amount crosses into the alveolar space where this fluid evaporates.
How does interstitial pulmonary edema form?
When the capacity of lymphatics to handle fluid leaking into the interstitium is saturated.
How does alveolar pulmonary edema form?
If interstitial pressure rises sufficiently from a present edema to rupture the alveolar epithelial membranes, then the alveoli flood. This is airspace disease.
How does alveolar pleural effusion form?
Accumulation of liquid in the interstitium when the lymphatics are saturated and can’t act as a pump.
Units of gas content
Litres /L
What is Henry’s law?
Gases dissolve in liquids by amounts that are in direct proportion to their partial pressures.
The partial pressures of the gas inside the liquid and outside of it equilibrate.
P = kC
Volume of O2 dissolved in the blood for each mm Hg PO2.
0.003 mL O2 / 100 mL of blood
Characteristics of Hb
- 4 polypeptide chains
- Each chain has a heme group containing Fe
- 1 O2 molecule can bind /heme group
What is the Hb binding capacity constant?
1.39 mL / g
Meaning that 1g of Hb can bind 1.39 mL of O2.
Equation of O2 bound to Hb
= Hb binding capacity x Saturation of Hb in O2 x [Hb]
Why is CO poisonous?
It has the same binding sites on Hb as O2, but a much higher affinity (>200x). This means that CO will combine with Hb at much lower partial pressures.
CO binding to Hb shifts the HbO2 curve to the _____.
LEFT.
3 ways to carry CO2 in the blood
- dissolved (5-10%)
- plasma bicarbonate (70-80%)
- carbino compound (HbCO2) (5-10%)
What enzyme facilitates the reaction converting CO2 and H2O to HCO3- and H+?
Carbonic anhydrase
What is the chloride shift?
The exchange of HCO3- to enter the plasma for Cl- to enter the RBC via an ion transporter on the RBC membrane.
Nearly all HCO3- is made in the RBC.
True or False? CO2 content in blood is linear to CO2 partial pressure.
True.
What do shifts to the left vs shifts to the right mean in terms of the HbO2 dissociation curve?
Left: makes it more difficult to unbind O2 (bigger drops in O2 pressure are needed).
Right: makes it easier to unbind O2.
What makes the O2 dissociation curve shift to the left?
Decreased temperature
Increased pH
Decreased CO2
Decreased 2,3 PDG
What makes the O2 dissociation curve shift to the right?
Increased temperature
Decreased pH
Increased CO2
Increased 2,3 PDG
What is the Haldane effect?
Increased loading of CO2 on deoxygenated Hb (= increased CO2 carrying capacity of the blood)
What is diffusion proportional and inversely proportional to?
Proportional: area, solubility, pressure gradient
Inversely proportional: molecular weight, thickness
How much time do the RBCs spend in pulmonary capillaries? How long does it take for blood PO2 to equilibrate with alveolar PO2 at rest ?
0.75s
0.25s
Between CO and O2, which is diffusion limited and which is perfusion limited?
O2 is perfusion limited
CO is diffusion limited
How do we measure diffusing capacity?
Using CO.
Single breath method.
Normal diffusing capacity is about 25 mL / min /mm Hg
What can decrease DLCO?
Emphysema
Interstitial lung disease
Pulmonary vascular disease
Anemia
What can increase DLCO?
Increased pulmonary capillary blood volume
Pulmonary hemorrage
Polycythemia
Asthma
Where is the respiratory pacemaker located?
In the pre-Botzinger complex, in the medulla. Opioids and fentanyl act directly on this structure to modulate breathing pattern.
What is the parafacial respiratory group also called? What is the role of this structure?
It is also called the retrotrapezoid nucleus. Its role is to sense CO2 levels. It is closely located to the pre-Botz complex.
What is the main sensor for O2 levels? What is its structure?
The carotid body.
Innervated by the carotid sinus nerve (branch of the vagus nerve) which projects into dorsal respiratory group.
Structure:
Type 1 = Glomus cells
Type 2 = Sustentacular cells
NF = Fibres of carotid sinus nerve
Describe the mechanism through which Glomus cells react when sensing low O2 levels.
Hypoxia = Ca2+ current in the glomus cell = depolarization = dorsal respiratory group stimulation.
This is because HO-2 is inhibited, so no CO is produced, so CSE produces H2S, which blocks K+ channels and allows Ca2+ inward current.
How are CO2 levels detected in the brain?
CO2 diffuses across the blood-brain barrier into the cerebrospinal fluid and converts to H+ + HCO3-. Elevated H+ levels activate the central chemoreceptor.
This is sensed at the RTN.
What is the ventilatory pattern response to hypoxia?
Rapid, shallow breathing. More increase in frequency than in tidal volume.
This minimizes the O2 cost of breathing.
What is the ventilatory pattern response to hypercapnea?
Deep, slow breathing. More increase in tidal volume than frequency.
This minimizes the dead space ventilation to optimize CO2 elimination.
Where do the afferents from the lungs and airways come into, to modulate breathing?
They are innervated by the vagus nerve (cranial nerve X), and come into the dorsal respiratory group.
Name two mechanoreceptors for breathing
Pulmonary stretch receptors
Juxtacapillary receptors
They are all vagal afferents.
What is the role of vagal afferent feedback?
To terminate inspiratory drive.
Name some chest wall mechanoreceptors for breathing feedback (3).
- Muscle spindles
- Golgi tendon organs
- Proprioreceptors
How do the upper airways provide feedback to the breathing center?
Through the glossopharyngeal IX nerve. They provide information about pressure and flow to central controller.
What is hyperventilation?
Reduced PaCO2
What is hypoventilation?
Increased PaCO2
What are eucapnic levels?
35-45 mm Hg
Name 5 causes of hyperventilation
- Metabolic (acidosis, liver disease, hyperthyroidism)
- Drugs
- CNS
- Lung disease (asthma, fibrosis, pulmonary edema, PE)
- Psychogenic
Name 5 causes of hypoventilation
- Metabolic (alkalosis, hypothyroidism)
- Drugs
- CNS
- Respiratory pump (neuromuscular disease, chest wall abnormalities)
- Parenchymal lung disease
What is Ondine’s curse?
Congenital Central Hypoventilation Syndrome.
Shown to be due to polyalanine repeat mutations in Phox2b. This mutation is primarily expressed in the cells of the ventral medullary surface (RTN).
This showed that RTN is the main site for CO2 sensitivity.
Why can PaCO2 worsen upon high FiO2 administration?
- High FiO2 blunts hypoxic ventilatory drive
- High FiO2 reaches even poorly ventilated alveoli, undoing hypoxic pulmonary vasoconstriction.
- Haldane effect
Why is PAO2 lower than PiO2?
Because PAO2 reflects a balance between the rate of delivery of O2 to the alveoli and the rate of O2 uptake by alveolar capillary blood.
What is the A-a difference?
It is a measure of gas exchange efficacy.
Normally, very small (5-10 mm Hg).
5 causes of hypoxemia
- Shunt
- Diffusion limitation
- Low V/Q
- Decreased PiO2
- Hypoventilation
When blood with low O2 content mixes with blood with high O2 content, the PO2 of the resulting mixture is…
Disproportionately pulled down by the blood that has low PO2.
How does V/Q vary from the top to the bottom of the lungs?
Both perfusion and ventilation are affected by gravity: both lower at the top and higher at the bottom. However, blood flow increases more as we go down the lung than the increase in perfusion.
Hence, the ventilation perfusion ratio decreases as we move down the lung.
There is v/q mismatch (normal) all throughout the lungs.
What are the two extremes of V/Q mismatch?
- Shunt = no ventilation. V/Q = 0. The arterial blood = venous blood in terms of O2 content.
- Dead space = no perfusion. V/Q = infinity.
2 types of shunt
- Pulmonary shunt
- Extra-pulmonary shunt: blood that bypasses the pulmonary circulation altogether.
Name 2 normal extra-pulmonary shunts
- Thesebian veins
- Bronchial circulation
