Normal Physiology Flashcards
What are the 3 main functions of the lungs?
Oxygenate pulmonary arterial blood
Remove CO2 from blood
Maintain acid-base balance
What is the most plentiful acid in the body?
CO2
What is the body’s rate of consumption of O2 and production of CO2 at rest (BMR)?
Uses 250mL/min O2
Produces 200mL/min CO2
What is the body’s rate of consumption of O2 and production of CO2 during exercise?
Uses >4000mL/min 02
Produces >4000mL/min CO2
Is oxygen carriage adequate to meet metabolic needs at rest and during exercise? How?
At rest, the total blood O2 content is ~200mL/L of blood, which with a resting CO of 5L/min results in a tissue oxygen delivery of ~1000mL/min
This is 4x the O2 requirement (250mL/min) of tissues at rest, which ensures that tissue oxygen delivery can be increased to 4000mL/min (as required in exercise) with only a 4x increase in CO
List 4 factors tissue oxygen supply is dependent on
PaO2
[Hb]
CO
Local tissue factors (e.g. temperature, pH, tissue vascularity, tissue pO2)
How many molecules of O2 can Hb bind?
Up to 4
How is Hb saturation calculated?
Hb saturation = (O2 combined with Hb/O2 capacity) x 100
What is the driving pressure for O2 binding to Hb?
Concentration of O2 dissolved in plasma (PaO2 or PvO2)
Amount of O2 that binds is proportional but not linear (due to changes in the conformational state and therefore affinity of O2 binding that occurs in Hb)
What are the 3 forms in which CO2 is transported and the relative proportions of each?
Dissolved - 10%
Attached to proteins (including Hb) as carbamino compounds - 30%
Bicarbonate - 60%
How is bicarbonate produced from CO2?
CO2 + H20 > H2CO3 > HCO3- + H+
In RBCs under the action of carbonic anhydrase
List 4 important characteristics of the A-C membrane that make it ideal for gas exchange (thickness, SA, alveolar and capillary volume)
Thin
Large SA
Alveolar volume 3-6L
Capillary volume 80mL (higher with increased CO)
Describe the partial pressures of O2 and CO2 during gas exchange at the lungs and in the tissues
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What is Fick’s law?
Equation used to calculate the rate of diffusion of a gas
Takes into account SA and thickness of membrane, difference in partial pressures, and the solubility and MW of the gas being exchanged
What determines the difference in diffusion rate between CO2 and O2?
CO2 is much more soluble than O2
What is the diffusion rate of CO2 compared with O2?
Diffusion rate of CO is 20x that of O2
How fast does diffusion of O2 occur?
Fast - in 0.25 seconds
What is the significance of the speed of diffusion of O2?
At rest, blood spends 0.75 secs in the capillary, but spends 0.25 secs in the capillary during exercise
Diffusion occurs in 0.25 secs so that O2 transfer is not limited
What is the limiting factor in O2 diffusion?
Perfusion
When is gas exchange most efficient?
When ventilation and perfusion are matched (V/Q = 1)
How is V/Q assessed clinically?
Ventilation scan: radioactive, non-absorbable particles are inhaled
Perfusion scan: radioactive particles are injected into a systemic vein and lodge in the small pulmonary arterioles
The 2 are compared
When does diffusion limitation occur for CO2?
Only with very severe abnormalities of the A-C membrane (or during exercise with less severe disease)
What generally causes an elevated PaCO2?
Inadequate alveolar ventilation (which decreases the partial pressure gradient for exchange)
What are the 4 components of the upper airway?
Nose
Mouth
Pharynx
Larynx
List 3 important characteristics of the trachea and main bronchi which aid lung function
Cartiginous support
Ciliated columnar epithelium
Mucociliary escalator
How many generations of airways are there (formed by branching of bronchi and bronchioles)? What is the significance of this?
22-23
Large increase in SA for gas exchange
Which of the 23 branchings are strictly conductive and which have alveoli in the walls?
First 17 are conductive
Last 6 contain alveoli
What respiratory muscles are used in normal inspiration and expiration?
Diaphragm and external intercostals (contraction causes inspiration, relaxation causes passive expiration)
What respiratory muscles are used in active expiration?
Internal intercostals and abdominal muscles
What are the accessory muscles of respiration?
Sternocleidomastoid and scalenes
What is the pleural space?
A (normally) potential space between the lungs and the chest wall
How does inspiration work?
Contraction of the diaphragm increases longitudinal and lateral dimensions of the thorax
Contraction of external intercostals increases the AP diameter of the thorax
This generates negative intrapleural pressure and sucks air into the lungs
Which nerves innervate the muscles of inspiration?
Diaphragm by phrenic nerve
External intercostals by intercostal nerves
What changes occur with very active inspiration?
Accessory inspiratory muscles raise the sternum and elevate the first 2 ribs to enlarge the upper thorax, generating a greater negative intrapleural pressure to increase inspiration
What pushes air out in normal expiration?
Inspiratory muscles relax and the elastic recoil of the lungs generates a positive intrapulmonary pressure, pushing air out
Describe the patterns of lung volumes during breathing
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TLC - total lung capacity, ~5.7L
RV - residual volume, volume left in lungs at maximum exhalation, ~1.2L
FVC - vital capacity, volume of air exhaled from TLC to RV, ~4.5L
TV - tidal volume, volume of any breath, 0.5L at rest
FEV1 - forced expiratory volume in 1 second, ~70-80% of FVC
FRC - functional residual capacity, volume remaining after passive exhalation (balance between elastic lung recoil and chest wall), ~2.2L
What are the 2 forces that must be overcome to achieve inspiration?
Resistive
Elastic
Describe airway resistance through the generations of bronchi
Maximum airway resistance in the segmental bronchi
Low resistance in the small airways because of the very large number of small airways (can be increased in disease that reduces their diameter or number)
What determines the elastic properties of lungs?
Their compliance (change in volume relative to change in pressure)
What is respiratory distress?
Increased work of breathing
What factors might increase elastic work of breathing vs. resistive work of breathing?
Elastic WOB: increased with decrease compliance
Resistive WOB: increased with obstruction of airways
Where are the central chemoreceptors located and what do they respond to?
On ventral medulla, surrounded by CSF
Respond to CSF [H+] (reflects CO2 in cerebral capillaries)
What receptors in the lung and other body sites can respond to stimuli to alter respiration?
Pulmonary stretch receptors Irritant receptors J receptors Upper airway receptors Joint and muscle receptors Nociceptors
What is the effect of temperature, pH and 2,3-BPG on the oxygen saturation curve
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What accounts for the difference in SBP during inspiration compared with expiration?
Decreased intra-alveolar and intrapleural pressure during inspiration causes decreased return of blood to the left side of the heart, resulting in a lower SBP during inspiration
What is the Alveolar-arterial (A-a) gradient for oxygen? How is it calculated?
Measure of the overall efficiency of gas exchange against all A-C units
Can measure PaO2 but PAO2 is estimated using the ideal gas equation (PAO2 = PiO2 - PACO2/RG, where PiO2 = 150, RQ = 0.8, and PaCO2 = PACO2)
A-a gradient = PAO2 - PaO2
What is the normal range for the A-a gradient?
<15-30
What are the applications of the A-a gradient in diagnosing pathology?
If the A-a gradient is high, this demonstrates the patient is hypoxaemic due to a gas exchange abnormality
What changes occur to the pulmonary circulation with exercise?
Pulmonary artery pressure (PAP) does not rise during exercise due to dilation and recruitment of pulmonary vessels
What is the normal pulmonary artery and capillary pressure?
Low pressure system
PAP: 25/8mmHg (mean of 15mmHg)
Capillaries: 12-8mmHg (from arterial to venous end)
What are the 3 factors determining fluid movement across the pulmonary capillaries?
Hydrostatic pressure inside and outside the capillary (Pc and Pi; usually Pc>Pi)
Oncotic pressure inside and outside the capillary (Oc and Oi; usually Oc>Oi)
Permeability of the capillary
What is the normal lymphatic flow in the lung? What is the significance of this?
~20mL/hr
If there is more fluid than this in the interstitial space, it will not be able to be cleared and will accumulate and eventually flow over into the alveoli
Describe the permability of the capillary endothelium compared with the alveolar epithelium
Capillary endothelium: highly permeable to water, ions and small molecules (not protein)
Alveolar epithelium: not permeable, actively pumps water into interstitial spaces
What are the 5 components of the A-C membrane?
Layer of surfactant Type 1 alveolar cell Basement membrane (can be 2 BMs with intervening CT) Vascular endothelial cell Plasma
How is movement of fluid between alveoli and interstitium prevented?
Tight junctions
Surfactant
What prevents collapse of alveoli?
Surfactant reduces surface tension
What is surfactant?
Group of closely related phospholipids
Which cells secrete surfactant?
Type II pneumocytes
What are the functions of surfactant?
Prevents collapse of alveoli
Increases lung compliance
Helps to keep alveoli dry
What is the role of the conducting respiratory system?
Carries and humidifies air
Describe the characteristics of respiratory epithelium
Pseudostratified ciliated columnar epithelium
What cell types are found in the respiratory epithelium and what are their roles?
Ciliated columnar cells: move mucus
Goblet cells: secrete mucus
Basal (stem) cells: in base of epithelium, renew epithelium
What are the 3 layers of the trachea and what are their relative compositions?
Mucosa: respiratory epithelium and lamina propria
Submucosa: glands and CT
Adventitia: cartilage and outer CT
Contrast the cartilage structure in the trachea with that of the bronchi
Trachea: C-shaped cartilage bridged by smooth muscle posteriorly
Bronchi: plates of cartilage
Where is the smooth muscle in the bronchus?
Boundary between the lamina propria and submucosa
What is the distinguishing feature of a bronchiole?
Lacks cartilage
What changes occur over the length of the bronchioles?
Respiratory epithelium loses goblet cells and ciliated columnar cells, gains Clara cells
Why do ciliated cells extended further down into the bronchioles than goblet cells?
To pick up any deeper mucus
Describe the structure of the bronchioles
Varying proportions of ciliated epithelium and goblet cells
Radial CT
Smooth muscle
What are Clara cells? What is their role?
Columnar to cuboidal cells with short microvilli Secrete surfactant (detergent-like glycoprotein)
Describe the structure of the terminal bronchioles
Cuboidal epithelium with some cilia
Clara cells
1 or 2 layers of smooth muscle
What is the epithelium of the respiratory bronchiole?
Cuboidal to squamous
Describe the structure of the alveolus
Simple squamous epithelium
Walls contain many pulmonary capillaries
Connected to other alveoli by pores
What is the role of the interalveolar pores?
Allow air to equilibrate
Describe the structure of the interalveolar septa and how this relates to function
Contains reticular and elastin fibres
Elastin keeps alveoli from collapsing
What are type I pneumocytes? What is the role of type I pneumocytes and what are their characteristic features?
Simple squamous epithelium
Forms the majority (95%) of SA of alveoli and acts as the exchange surface
Tight junctions to limit ECF leakage and prominent basal lamina
What are type II pneumocytes? What is the role of type II pneumocytes and what are their characteristic features?
Cuboidal cells often found in the angle between alveoli
Secrete surfactant-containing lamellar bodies and also act as local SC to produce type I and II pneumocytes
Short microvilli and lamellar bodies
What is the fate of the interalveolar macrophages?
Migrate up airways to be carried off by mucociliary escalator
Some macrophages take up residence in interalveolar septum
Describe the structure of the pleura
Simple squamous mesothelium supported by basal lamina and fibrous CT
Serous fluid in space potential space between visceral and parietal pleura provides lubrication
What is the significance of the pleural space in lung pathology?
Lymphatics drain here (can drain bacteria, cause pleuritis, or cancer cells)
