Alveolar Ventilation and gas exchange

Why is the Total pressure @ lungs is 713 mmHg but the pressure at the atmosphere is 760?

This is because of water vapor. At the lung (wet surface), water vapor exists and displaces the gases. In this example, @ 37 ̊C (body temp), P_H2O = 47; Thus 760-47=713

Given that the partial pressure @ lung surface:

• P_O2 = 149.7

• P_CO2 = 0.28

Explain the Partial Pressures of O2 and CO2 @ Alveolar and why these concentrations are different when Expired (@mouth):

• Alveolar Air: P_O2 = 104 mmHg P_CO2 = 40 mmHg

• Expired Air: P_O2 = 120 mmHg; P_CO2 = 27 mmHg

Alveolar Air:

• P_O2 is lower then atmosphere b/c:

  • Alveolar air is only partially replaced by atmospheric air

  • O2 is constantly diffusing from the alveoli into the blood

• P_CO2 is higher then atmosphere b/c:

  • CO2 is constantly diffusing into the alveoli from the blood

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Expired Air:

• P_O2 is Higher then @ Alveolar Air b/c:

  • Alveolar air is mixed with dead space atmospheric air

  • O2 concentration is higher is atmospheric air than alveolar air

• P_CO2 is Lower then @ Alveolar Air b/c:

  • CO2 concentration is lower in atmospheric air than alveolar air

What determines P_gas in a fluid (ie. blood)?

• Using this logic, why is P_O2 > P_CO2

Henry's law: Pgas (in fluid) = [gas]/solubility

• CO2 is 20X more Soluble then O2; thus will have a lower pressure in fluid.

Describe the change in partial pressure in O2 and CO2 as you go from the mouth (atmosphere) down to the alveolar and explain why this occur.

Mixing of atmospheric air with dead space air and alveolar air creates a fall in PO2 and a rise in PCO2 by the time air reaches the alveoli

1. What is V_E and what is the formula

2. What is V_A and why is it lower then V_E

3. How can you estimate V_A ?

4. What can reduce/enhance V_A

Minute ventilation (V_E):

• Total air volume exchanged (inhaled or exhaled) by the entire lung per minute

• V_E = V_T x f

  • V_T= ml of air per breath

  • f = breaths/min

  • Ex: 500 ml/breath x 15 breaths/min = 7500 ml/min (average 70kg male)

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Alveolar ventilation (V_A):

• total air volume exchanged by the alveoli per minute

• V_A < V_E b/c of Anatomic Dead Space (V_D)

  • Anatomic Dead Space: conducting airways do not contain alveoli and do not participate in gas exchange*

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Estimations:

• V_D is roughly: ~ 1 ml V_D /lb body weight

• V_A = V_T - V_D x f

• Rapid & shallow breathing pattern reduces V_A

• Slow and deep breathing pattern enhances V_A

Compare and Contrast Anatomical/Physiological Dead Space

Anatomical Dead Space: refers to the fact that the conducting portion of the lungs can’t engage in gas exchange;

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Physiological Dead Space: when pulmonary flow to a portion of alveoli is obstructed (Ex: pulmonary embolism) → thus that affected alveoli can’t exchange gas → dead space

1. What factors influences P_AO2

2. What is the formula for P_AO2?

P_AO2 = [O2] entering - [O2] leaving; Determined by:

• inspired oxygen, P_IO2

• alveolar ventilation rate V_A

• PAO2 is directly proportional to PIO2 and VA

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P_AO2 = P_IO2 – P_ACO2/R

• R = respiratory gas quotient (VCO2/VO2)

  • If Carbs: R = 1 b/c tissues produce 1 CO2 for each O2 consumed

  • If Fat: R = 0.70 b/c ~ 16 CO2 are produced for every 23 O2

  • Under normal circumstances R is estimated at 0.8

    • If R > 1; More CO2 is produced then O2 consumed

    • If R < 1; less CO2 is produced then O2 consumed

1. Draw out the graph depicting Alveolar Partial Pressure of O2 and Ventilation Rate given a O2 uptake of 250 vs 1000 ml O2/min

2. Explain the graph

As you can see, there is a direct relationship between ventilation rate and alveolar partial pressure of Oxygen; 

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Also, if you increase the O2 uptake for some reason (in this case,

b/c you’re exercising and need more O2); then you need to increase the ventilation rate in order to get back down to physiological O2 partial pressure. This is b/c w/ more O2 , you need to increase  frequency of ventilation to diffuse more O2 (into blood)

1. What is the formula for P_ACO2?

2. What is  P_ACO2 determined by?

P_ACO2 = VCO2/ VA:

• directly proportional to CO2 production by the tissues

• inversely proportional to VA

  • during ventilation, CO2 leaves lung/alveoli

1. Draw out the graph depicting Alveolar Partial Pressure of CO2 and Ventilation Rate given a CO2 uptake of 200 vs 800 ml O2/min

2. Explain the graph

As you can see, there is an inverse relationship between Partial Pressure of CO2 and Ventilation rate

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Also, the graph is shifted to the right in the presence of more CO2 in the Alveoli/min; This is because ventilation has to increase to match the increased CO2 in the alveoli

1. Describe how metabolism affects O2 and CO2?

2. How can Gas transport imbalances occur?

Metabolism:

• ↑ metabolism → ↑ O2 consumption → ↑O2 delivery

• ↑metabolism → ↑CO2 production → ↑CO2 removal

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Gas transport imbalances:

• amount of O2 and CO2 used and produced by tissues must exactly match the amount of O2 and CO2 that enters and exits the lungs

• Imbalance results from lung disease or exercise

  • ↓Blood [O2] = hypoxemia

  • ↑Blood [CO2] = hypercapnia (acidosis)

Describe the layers that gas has to diffuse through in the respiratory system

Layers of the membrane

• Layer of fluid mostly surfactant

• Alveolar epithelium

• Epithelial basement membrane

• Thin interstitial space between alveoli and capillary

• Capillary basement membrane

• Capillary endothelial membrane

What are three factors that affect equilibration?

• Diffusing properties (Fick’s law)

  • (membrane and gas)

  • Ficks equation in the lung

• Equilibrium time

• Blood carrying properties (ie Hemoglobin)

Describe Fick’s Law

• DeltaP: partial pressure difference of the gas across the membrane

• Area: surface area available for diffusion

• Thickness: thickness of the membrane.

Describe how properties of the membrane varies during respiration cycle

Area/Thickness:

• Inspiration: Stretch maximizes Surface Area and minimizes Thickness

• Vice Versa

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Pressure Gradient:

• @ end of inspiration: influx of air → maximizes PO2 and minimizes PCO2

Why is the equilibrium time for O2 and CO2 same despite O2 having a much steeper pressure gradient?

Although partial pressure differences for CO2 are less, due to its
solubility it diffuses about 20 times more rapidly, therefore, it reaches
equilibrium in the capillary bed at about the same time as O2

Describe the consequences of:

• Hypoventilation

• Hyperventilation

Hypoventilation:

• hypercapnia and can lead to acidemia (↑H+ ion)

Hyperventilation:

• results in hypocapnia and can lead to alkalemia (↓H+ ion)

What are the three forms of O2 in blood? How much O2 is dissolved in plasma?

Forms:

• Dissolved O2

  • 15 mlO2/min

• PO2

• Bound O2

If O2 can travel through any membrane, Why do we need Hb?

This is b/c O2 has low solubility in plasma (15 mlO2/min); In theory, we can/do use this dissolved O2, but the average 70K human needs 250 mlO2/min at rest; Hb solves this.

[REVIEW] Properties of Hb

Differentiate between myo and hemoglobin

Hb:

• restricted to erythrocytes

• heterotetrameric protein

• four O2 binding sites

• O2 transport from lung to tissues

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Mb:

• found in striated and skeletal muscle

• Monomeric – one O2 binding site

• stores O2 in cytoplasm

• delivers O2 to mitochondria on demand

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Note the difference in saturation curves; Hb has a sigmoidal curve b/c of its cooperative characteristics

A person is offering you a can of pure O2, stating that this extra O2 will greatly benefit your body. Why is this BS?

you can have as much O2 as you want, but at some point, Hb will be saturated to 100% and that excess O2 can’t be put to actual use.

List the 4 mechanisms that alters O2 transport

• Blood flow (HR x SV)

• a-v O2 difference

• O2 capacity (Hb content)

  • Anemia: a deficiency of Hb

  • Polycythemia: an increase in Hb

• Shifting of the curve (Bohr effect)

  • Partial pressure of CO2

  • pH or H+

  • Temperature

  • 2,3 diphosphoglycerate (2,3 DPG)

Describe the positive/negative allosteric effector that affects the oxyhemoglobin dissociation curve

Describe the Bohr effect and mechanism

Bohr Effect: decreasing pH → decreaes Hb’s Affinity to O2 (right shift):

• Mechanism:

  • @ lung Alveoli: O2 binding to Hb releases H+

    • This is b/c when O2 binds, Hb transition from Taut (T) → Relaxed (R) state → This releases H+ which used to stabilized the Taut State

    • This H+ then combines w/ HCO3- to make CO2 to be exhaled

  • @ Tissue capillary beds: Increased [H+] → enhances O2 release for aerobic metabolism

Describe the effect of CO2 and mechanism

CO2: decreases affinity of Hb for O2

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Mechanism:

• Increased PCO2 in venous capillaries

  • Hb-NH2 + CO2 ↔ Hb-NH-COO- + H+

    • carbamino-Hb (Hb-NH-COO) decreases O2 affinity

  • CO2 → Lungs as Carbamate + HCO3-

    • erythrocyte carbonic anhydrase → Carbamic Acid (H₂N-COOH) → provides a source of H+ for Bohr Effect → further decreases O2 affinity

• Decreased PCO2 at the lungs

  • CO2 released from N terminus of Hb (increases O2 affinity)

  • Reversal of carbonic anhydrase rxn

1. Describe the effect of 2,3-bisphosphoglycerate and mechanism

2. What happens in hypoxia?

erythrocyte 2,3-BPG is negative allosteric effector of Hb that increases P50 (decreases Hb-O2 affinity)

• without 2,3-BPG, Hb has Mb O2 saturation curve

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Mechanism:

• negatively charged 2,3-BPG binds to central site between B1 and B2 subunits → stabilized T-state → low O2 affinity 

• Increase in P02 → central pocket collapses, releasing 2,3-BPG

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Hypoxia:

• decrease PO2 → increases in 2,3-BPG → stabilizes deoxyHb → more O2 released to hypoxic tissues

Why is carbon monoxide dangerous?

Dangers of CO:

• Affinity:

  • CO can bind to Hb w/ an affinity 250X stronger then O2 → Cooperativity causes other sites to have an even stronger affinity to CO → O2 can’t bind

  • Hb-CO liberates CO very slowly.

  • Makes it Hard for O2 to liberate as well

  • Left-Shift

• Hard to Detect:

  • symptoms of CO poisoning are those of any type of hypoxia, especially headache and nausea

  • oxygen content of blood is greatly reduced but PO2 of the blood may be normal.

    • the normal PO2 → carotid and aortic chemoreceptors does not illicit a respiratory reaction

  • blood is bright red and there are no obvious skin signs of hypoxemia

  • ***Death results when about 70-80% of the circulating hemoglobin is converted to Hb-CO.***

Describe the regulation of Hb Production

Kidney senses local tissue hypoxia → releases erythropoietin (EPO*) → travels to bone marrow → stimulate differentiation of
hemotapoietic stem cells

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*= a peptide hormone that works through tyrosine kinase receptors 

How is CO2 transported?

• Gaseous and dissolved CO2 in plasma

• Carbamino compounds: Hb-NH-COO- + CO2

• Bicarbonate (HCO3-)

Describe the Haldane Effect

O2 bonds Hb at lungs it becomes a stronger acid → Displaces CO2 b/c:

• Acidic Hb has less affinity for CO

• Increased acidity causes release of excess H+ ions which bind with HCO3 → carbonic anhydrase rxn

Describe the steps of gas transfer from tissue to plasma

1. Oxidative metabolism in tissue

   • O2 unloading to meet demand

   • CO2 in tissue moves into plasma

2. Formation of bicarbonate

   • slow in plasma; Fast in RBC via carbonic anhydrase

3. Setting up gradients

   • more HCO3- diffuses out compared to H+

   • sets up an electrical gradient

4. Haldane and Bohr effects

   • formation of carbamino-Hb with continued desaturation of Hb

   • reduced Hb is strong proton acceptor, binds H+
     forming acid Hb

5. Chloride shift

   • to maintain electroneutrality Cl- moves from
     plasma into RBC

   • this results in greater ion concentration within
     RBC therefore H2O also enters RBC

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All steps reversed @ Lung