O2 transport and Regulation (Lectures 29,30,31)

Ventilation-Perfusion Matching (V/Q)

Refers to coordination between amount of air (ventilation) reaching the alveoli and the amount of blood (perfusion) flowing

Sequence of oxygen movement

Atmospheric O2

• Affected by altitude, humidity

Alveolar O2

• Affected by lung compliance, airway resistance

Plasma O2

• Affected by factors affecting diffusion (membrane thickness, excess liquid) 

HbO2

• Each step determines next/one way

What is responsible for O2 and CO2 pressure gradients?

Us living and existing is responsible for driving pressure gradients with use of O2 and production of CO2

O2 vs CO2 pressure gradient

• O2 gradient from alveoli to tissue that drives oxygen movement

• CO2 gradient is opposite as higher pressure in tissue and lower in alveoli since CO2 is waste production of metabolism

What enters the pulmonary capillary (conducting airway) and what leaves?

O2 enters

CO2 leaves

What blood comes from right heart and what blood goes to left heart?

Mixed venous blood from right heart (pretty equal PVO2 and PVCO2)

Systematic arterial blood to left heart (PaO2=100, PaCO2=40)

Steps for Gas Exchange

1. Oxygen needs to reach alveoli

2. Oxygen needs to diffuse across

3. Oxygen needs to reach blood

Alveolar Gas Exchange influenced by

1. O2 reaching the alveoli

• Composition of inspired air

• Alveolar ventilation: affected by rate and depth of breathing, airway resistance, lung compliance

2. Gas diffusion between alveoli and blood:

• By surface area

• By diffusion of distance: affected by barrier thickness and amount of fluid

3. Adequate perfusion of alveoli

Total peripheral resistance (TPR) is regulated by arteriolar radius, which is regulated by

1. Local control

2. Reflex control

Local control of arteriolar radius is regulated by

1. Myogenic responses

2. Paracrines

a. Metabolic - O2, CO2

b. Signal molecules - NO

c. Immune cells - Histamine

Reflex control of arteriolar radius is regulated by

1. neural

• Sympathetic on arterioles (norepi on alpha)

2. hormonal

• epi on beta2

• angiotensin II

• ADH (vasopressin)

• ANP

In peripheral and systemic system, local factors of O2 and CO2 affect arterials by:

If low O2 and high CO2 in peripheral tissue = hints at lots of metabolizing

This is sensed by arterioles —> vasodilate —> get more oxygen to supply skeletal muscle

If high O2 and low CO2 in peripheral tissue = hints at low metabolizing

This is sensed by arterioles as body does not want to waste O2 —> vasoconstrict

Goal of systemic and peripheral system managing O2 and CO2 arteriolar radius is to:

Optimize tissue oxygenation

In pulmonary system, local factors of O2 and CO2 affect arterials by:

If low O2 and high CO2 —> pulmonary arterioles vasoconstricts —> why waste in not ventilated area, go to lungs that are well ventilated

If high O2 and low CO2 —> pulmonary arterioles vasodilates —> enough oxygen in body, go divert blood in areas that are oxygen rich

Goal of pulmonary system managing O2 and CO2 arteriolar radius is to:

Optimize gas exchange

Lungs do not want to waste perfusion to poorly ventilated areas

What is ideal ventilation/perfusion matching (V/Q)?

0.8

Avg aleolar ventilation (air flow) = 4 L/min

• Takes into account of dead space

Avg perfusion (blood flow) = 5 L/min

4/5 = 0.8

PAO2 = 

PaO2 =

PAO2 = alveolar oxygen pressure

PaO2 = arterial oxygen pressure

For gas exchange to be effective, what must happen between blood flow and air flow?

For gas exchange to be effective, blood flow (perfusion) must “match” air flow (ventilation

If one alveoli becomes underventilated:

• Decrease in PAO2 and increase in PACO2

• Pulmonary arteriole constricts in hypoxia

• Don’t want to send blood to poor ventilated area —> redirect blood elsewhere

If one alveoli is well ventilated:

• Increase in PAO2 and decrease in PACO2

• Pulmonary arterioles dilate in hypoxia

• Want to send body there to pick up oxygen

Total pulmonary ventilation (TPV) equation

TPV = Respiratory rate (RR) x Tidal volume

Avg RR = 12 - 18 br/min (about 15 br/min)

Avg TV/breath = 500 mL/br

Avg TPV = 6-9 L/min

Low V/Q Defects

• V lower than normal, Q not changing

• Perfusion (Q) is being wasted

• COPD (bronchitis or emphysema), pulmonary edema (liquid in alveoli)

• Body senses low ventilation as O2 is not reaching arterioles

• Means ventilation is issue —> oxygen not able to each alveoli

High V/Q Defects

• V is not changing, Q lower than normal

• Ventilation (V) being wasted

• Emphysema *

• Means perfusion is an issue → oxygen not able to reach blood

V/Q = 0

Shunt: no ventilation

Airwway obstriction, pneumonia

V/Q = infinite 

Q = 0 

Pulmonary embolism: clot from another place in the body which had lodged its way into lungs, capillaries, or bigger vessels 

Dead space

Low Ventilation Disorders:

High ventilation Disorders

Low Ventilation: Airway obstruction, Pneumonia, Obstructive Lung Disorder (Asthma, Bronchitis), Restrictive Lung Disorder

High Ventilation: Emphysema

Low perfusion disorders:

High perfusion disorders:

Low perfusion disorders: low cardiac output, pulmonary embolism

High perfusion disorders: N/A

The lower the V/Q ratio…

the closer the outflowing blood composition gets to mixed venous blood, aka true shunt

The higher the V/Q ratio….

the closer the outflowing blood composition gets to alveolar gas

Gas Composition	Bronchioles	Pulmonary Arterioles	Systemic Arterioles
PCO2 increases
PCO2 decreases
PO2 increases
PO2 decreases

Gas Composition	Bronchioles	Pulmonary Arterioles	Systemic Arterioles
PCO2 increases	Dilate	Constrict	Dilate
PCO2 decreases	Constrict	Dilate	Constrict
PO2 increases	Constrict	Dilate	Constrict
PO2 decreases	Dilate	Constrict	Dilate

O2 diffuses across from ___ into ___ into ___

alveoli —> plasma blood —> RBCs where O2 binds to hemoglobin

Total Blood oxygen (TBO) =

O2 dissolved in plasma (PaO2) about 2% + O2 bound to hemoglobin (HbO2) about 98%

Why does our body use O2 bound to hemoglobin and not dissolved O2?

Oxygen is not very soluble in liquid → poor at delivering good amount of oxygen to tissues

Hemoglobin

• Composed of 4 chains (2 light and 2 heavy)

• Each chain has heme group where oxygen binds to

• One hemoglobin can bind up to 4 oxygen molecules

If you do not have hemoglobin:

rely on dissolved oxygen for means of delivering oxygen to their tissue

• Normal amounts of oxygen reaching alveoli

• Low O2 carrying capacity

Equation of HbO2

• reversible reaction in order to offload oxygen to give to tissues

Relationship between partial pressure of oxygen (PO2) and amount of hemoglobin saturated with oxygen

Directly related

More oxygen around, more hemoglobin that is going to have oxygen bound to it

P₅₀

PO2 that corresponds to 50% saturation of hemoglobin

Does PO2 every reach 100%?

No, max is 98%

The oxygen hemoglobin disassociation curve shows what shape

S shape (sigmoidal) due to cooperative binding

cooperative binding: as more O2 binds to Hb, it increases affinity of Hb to O2

Why is Cooperative binding evolutionary/biologically advantageous and get selected for?

1. Hemoglobin is at 75% saturation when it returns to lungs, posessing the highest affinity to O2 - perfect for O2 binding to Hgb at the lungs

2. When there is less O2 bound, Hgb’s affinity to O2 decreases, so more O2 will unbind

• Perfect for when you need to offload O2 quickly

PO2 of arterial blood

PO2 at mixed venous pressure/at rest

PO2 of arterial blood = 100 mm Hg

PO2 at mixed venous pressure/at rest = 40 mm Hg

Factors changing affinity of Hb

Metabolic byproducts

1. CO2 (byproduct of cellular respiration)

2. pH (H+ byproduct of CO2 breakdown)

3. Temperature (byproduct of muscle movement)

4. 2,3 BPG (byproduct of metabolism)

How to unload O2?

• Decreases Hb affinity to O2 —> right shift

• Running away from tiger aka increased metabolic state where you are using lots of O2

• Increase CO2

• Low pH (increase H+)

• Increase 2,3 BPG

• Area below graph ahs gotten smaller which means less oxygen bound hemoglobin

• Higher PCO2, higher P₅₀

How to tightly bind o2?

• Increase Hb affinity to O2 —> left shift

• Decrease CO2

• Higher pH (decrease H+)

• Decrease temperature

• Decrease 2,3 BPG

• Area below graph has gotten bigger which means more oxygen bound to hemoglobin

• Lower PCO2, lower P₅₀

If you are running away from a tiger, do you want O2 bound more tightly to Hgb?

No, you want it to be loose and unloading oxygen

Effects of anemia

• Reduction in hemoglobin

• Decrease in hemoglobin = decrease in HbO2

• TBO decreased as same PaO2 but HbO2 decrease

You always equilibrate same amount of

oxygen in your plasma (PaO2) even if less more more hemoglobin

Effects of carbon monoxide poisoning 

• Extremely fatal as brain not getting oxygen supplied 

• Displaces oxygen off of iron in heme group

• Binds to heme group with very high affinity (200-300 times more than oxygen)

• Increases affinity of Hb for O2 that is bound

• Shifts curves in both directions

• Influences amount of oxygen bound to hemoglobin

• Sits at 50% saturation

Effects of altitude

At sea level

• PAO2 = 100 mm Hg

• PO2 = 160 mm Hg

• As you get higher in altitude, values declines

• Decreased O2 (dissolved oxygen)

Immediate response to attitude (hypoxia)

• Hyperventilation: chemoreceptor reflex activated at plasma PO2 = 60 mm Hg

• Systemic arteriolar dilation (low O2 thinks metabolizing a lot) and cerebral edema (collection of fluid in brain)

• Increased sympathetic output

• Pulmonary arteriole constriction (hypo ventilated) area) —> HAPE

Long term response to altitude (hypoxia)

• Increased erythropoietin (EPO) —> RBC synthesis (increase RBCs)

• Increase # mitochondria and mitochondria enzymes

• Increased myoglobin (muscle form of Hb)

• Angiogenesis (making more vascular/arterioles)

• Initially decrease in plasma oxygen and increase in Hb

Breathing is dependent on

skeletal muscles which do not contract spontaneously, but rely on somatic motor neuron/pacemakers in RCC in pons and medulla

Influences of rate of breathing

Carotid and aortic chemoreceptors detected by CO2, O2, and H+

• Integrated in medulla and pons

Emotions and voluntary control

Respiratory neurons in medulla

control inspiratory and expiratory muscles

Neurons in the pons

interact with medullary neurons to influence ventilation

DRG (Dorsal Respiratory Group)

• D for Diaphragm and DRG

• In medulla

• Regulates muscles for quiet inspiration

• NTS receives sensory information from peripheral chemo and mechanoreceptors through vagus and glossopharyngeal nerves (X and IX)

• Output from DRG goes via the phrenic nerves to the diaphragm and via intercostal nerves to intercostal muscles

VRG (Ventral Respiratory Group)

• V for VRG and Very forced breathing

• Active during forced inspiration and expiration

• Innervate muscles of larynx, pharynx, and tongue 

• Inappropriate relaxation of muscles constrictive to obstructive sleep apnea 

Pre Botzinger complex

• Part of VRG

• Contains spontaneously firing neurons which are pacemakers in RCC for respiratory rhythm

Medulla vs Pons function for respiration

Medulla: initiates respiration

Pons: modulates respiration

Chemoreceptor reflex function for respiration

modulates respiration

detects CO2, O2, and H+

Peripheral (carotid/aortic) chemoreceptors

• Detects CO2, O2, and H+

Central (medullary) chemoreceptors

Detects only H+ in CSF

Plasma levels of O2 need to be ___ in order to trigger chemoreceptor reflex

below 60 mm Hg

Steps for how chemoreceptors detect hypoxia

1. Low PO2 (PO2 drops below 60 mm Hg)

2. K+ channels close

3. Cell depolarizes

4. Voltage gated Ca2+ channels open

5. Ca2+ floods in

6. Exocytosis of neurotransmitters

7. Activates afferent fibers of CN IX

8. Sends signal to medullary respiratory centers

9. Ventilation increases