44- Carbon Dioxide Transport In Blood

define hypoxia

decrease in arterial PO2

5 ways an animal can become hypoxic

1. low inspired O2

2. hypoventilation

3. diffusion limitation

4. V/Q mismatch (ventilation - perfusion inequality)

5. right to left shunt 

describe 1. low inspired O2

• Cause: Reduced barometric pressure or low fraction of O₂ in inspired air.

• Effect: ↓ PAO₂ → ↓ PaO₂.

• A–a gradient: Normal (no ventilation-perfusion mismatch)

describe 2. hypoventilation

• Cause: CNS depression (anesthesia, drug overdose), airway obstruction, or neuromuscular disease.

• Effect: ↓ alveolar ventilation → ↑ PaCO₂ and ↓ PAO₂ → ↓ PaO₂.

  • A–a gradient: Normal (problem is global ventilation, not diffusion).

describe 3. diffusion limitation

• Cause: Thickened alveolar membrane (fibrosis, edema) or short capillary transit time (exercise).

• Effect: O₂ fails to equilibrate across the alveolar-capillary membrane.

• A–a gradient: Increased.

describe 4. V/Q mismatch (ventilation - perfusion inequality)

• Cause: Some lung regions are under-ventilated or under-perfused (e.g., asthma, pneumonia, COPD).

• Effect: Low V/Q regions dominate → mixed arterial blood has lower O₂.

• A–a gradient: Increased (most common cause of hypoxemia clinically).

describe 5. R to L shunt

• Cause: Blood bypasses ventilated alveoli (congenital heart defects, collapsed alveoli).

• Effect: Venous blood mixes with oxygenated blood → ↓ PaO₂ that cannot be fully corrected by O₂ therapy.

• A–a gradient: Markedly increased.

describe the A-a gradient

difference between the PO₂ of alveolar gas (PAO₂) and the PO₂ of arterial blood (PaO₂).

= PAo2 - PaO2

• tells you how well oxygen is transferring from alveoli → blood.

🔸 Normal = global ventilation problem (like hypoventilation)
🔸 Increased = local gas exchange problem (like V/Q mismatch, diffusion defect, or shunt)

ventilation/perfusion at the top (apex) of lungs

high

ventilation/perfusion at base (bottom) of lungs

low

describe zone 1 of lungs (dead space like)

Pressures: PA > Pa > Pv
Blood flow: Almost none – capillaries collapse
Ventilation: Low but still occurs
V/Q ratio: Very high (> 1)
Gas: ↑ PO₂ ↓ PCO₂
Notes: Seen at the top of upright lungs or when pulmonary pressure is low.

describe zone II - mid-lung (waterfall zone)

Pressures: Pa > PA > Pv
Blood flow: Intermittent – depends on Pa vs PA
Ventilation: Moderate
V/Q ratio: ≈ 1 (ideal gas exchange)
Gas: Normal alveolar values (PO₂ ≈ 100 mm Hg, PCO₂ ≈ 40 mm Hg)

describe zone III - base (shunt like)

Pressures: Pa > Pv > PA
Blood flow: Continuous – highest perfusion
Ventilation: High, but not as high as perfusion
V/Q ratio: Low (< 1)
Gas: ↓ PO₂ ↑ PCO₂
Notes: Gravity effect → most gas exchange occurs here.

overall describe the 3 lung zones

Apex → High V/Q → Dead-space-like
Middle → Normal V/Q ≈ 1
Base → Low V/Q → Shunt-like

describe HPV

When alveolar PO₂ (PAO₂) falls below about 70 mm Hg, the small pulmonary arterioles constrict.
This response is called hypoxic pulmonary vasoconstriction (HPV)

describe the 2 steps of HPV

1. Low PAO₂ causes depolarization of pulmonary vascular smooth muscle cells, which opens voltage-gated Ca²⁺ channels.

2. Ca²⁺ enters the cell, increasing intracellular Ca²⁺ and leading to smooth muscle contraction and vasoconstriction

is HPV unique to lungs

yes, in systemic tissues, hypoxia causes vasodilation, not constriction

purpose of HPV

HPV functions to match ventilation and perfusion (V/Q matching):

Blood is diverted away from poorly ventilated (hypoxic) alveoli toward better ventilated regions, optimizing gas exchange

role of Nitric oxide in HPV

• NO is an endothelial-derived relaxing factor, synthesized from L-arginine via nitric oxide synthase (NOS).

• NO activates guanylyl cyclase → cGMP production → smooth muscle relaxation.

When NOS is inhibited, HPV becomes stronger; conversely, inhaled NO blunts or reverses HPV

localized HPV

redirects blood flow away from diseased or fluid-filled alveoli.

global HPV

occurs when the entire lung is hypoxic (e.g., high altitude, low inspired O₂) → increases pulmonary vascular resistance and pulmonary arterial pressure.

describe chronic hypoxia and HPV

prolonged vasoconstriction leads to right ventricular hypertrophy from increased afterload

overall describe HPV and its effects

HPV is a protective mechanism that shunts blood from hypoxic alveoli, improving overall O₂ exchange.
NO normally relaxes pulmonary vessels; when its effect is reduced, hypoxic vasoconstriction strengthens

effect of low inspired O2 on pulmonary circulation like with high altitude

• barometric pressure drops, so the PO₂ of inspired air (PIO₂) and alveolar PO₂ (PAO₂) both decrease

• triggers hypoxic pulmonary vasoconstriction (HPV) throughout the entire lung (since all alveoli are hypoxic)

result of HPV from low inspired O2

• Increased pulmonary vascular resistance (PVR)

• Increased pulmonary arterial pressure (pulmonary hypertension)

• Right ventricular strain (from pumping against higher resistance)

how does high altitude disease occur with hypoxia

with continuing exposure to hypoxia,

• Thickening (hypertrophy) of smooth muscle in pulmonary arterioles

• Right ventricular hypertrophy (cor pulmonale) from sustained pressure overload

• Possible pulmonary edema due to capillary leakage from elevated pressures

describe low inspired O2 and chronic exposure as a whole

Low inspired O₂ at altitude causes global alveolar hypoxia → pulmonary vasoconstriction → pulmonary hypertension.
Chronic exposure can lead to right heart hypertrophy and high-altitude pulmonary disease, though long-term adaptation (hyperventilation and ↑ RBCs) helps maintain tissue oxygenation

describe the basic V/Q concept

Basic concept

• V = ventilation (airflow)

• Q = perfusion (blood flow)

• The V/Q ratio determines how efficiently O₂ and CO₂ are exchanged.

• In an ideal lung, V/Q = 0.8 (normal overall ratio).

Because of gravity, ventilation and perfusion are not uniform throughout the lung.

lung ventilation/blow flow areas

• Apex: efficient ventilation but little blood flow → resembles dead space.

• Base: good blood flow but less ventilation per unit → resembles a physiologic shunt.

• Middle zone: best overall gas exchange.

how do quadrupeds differ in their V/Q distribution

gravity acts along the dorsoventral axis (back to belly), not top to bottom.

• Dorsal (upper/back) regions: better ventilation relative to perfusion → higher V/Q.

• Ventral (lower/belly) regions: better perfusion → lower V/Q.

compare humans v quadrupeds V/Q

In humans: highest at the apex, lowest at the base.
In quadrupeds: highest dorsally, lowest ventrally.
This distribution maintains efficient gas exchange across the lung.

zone 1 - apex

• Ventilation ≫ Perfusion

• PO₂ ≈ 130 mm Hg ↑ (high)

• PCO₂ ≈ 28 mm Hg ↓ (low)

  • “Dead-space–like” — alveoli well ventilated, poorly perfused.

zone 2-  middle ( normal V/Q = 1)

• Ventilation ≈ Perfusion

• PO₂ ≈ 100 mm Hg

• PCO₂ ≈ 40 mm Hg

• Ideal gas exchange — balanced air & blood flow.

zone 3- Base (low V/Q = 0.6)

• Perfusion ≫ Ventilation

• PO₂ ≈ 89 mm Hg ↓ (lower)

• PCO₂ ≈ 42 mm Hg ↑ (higher)

• “Shunt-like” — blood flow high, ventilation relatively low.

zone 1 dorsal in quadrupeds

V/Q ≈ 3.0 (high)

• Ventilation ≫ Perfusion

• PO₂ ≈ 130 mm Hg, PCO₂ ≈ 28 mm Hg

• Dead-space–like: alveoli are well ventilated but underperfused.
  🐾 In quadrupeds:

Dorsal (upper/back) lung regions = relatively less perfusion due to gravity → higher V/Q, higher PO₂, lower PCO₂

zone 2- mid lung quadrupeds

V/Q ≈ 1.0 (ideal)

• Ventilation ≈ Perfusion

• PO₂ ≈ 100 mm Hg, PCO₂ ≈ 40 mm Hg

• Best gas exchange efficiency.
  🐾 In quadrupeds:

Mid-dorsal areas = balanced ventilation & perfusion, most efficient O₂/CO₂ exchange (similar to Zone II in upright humans)

zone 3- ventral quadrupeds

V/Q ≈ 0.6 (low)

• Perfusion ≫ Ventilation

• PO₂ ≈ 89 mm Hg, PCO₂ ≈ 42 mm Hg

• Shunt-like: blood flow high, ventilation proportionally lower.
  🐾 In quadrupeds:

Ventral (lower/belly-side) lung regions = gravity causes more blood pooling → lower V/Q, lower PO₂, higher PCO₂.