📖 Table Mentioned: Table 40.1

• Alveolar air does not have the same gas composition as atmospheric air.
• This difference occurs because of several reasons:
• First: With each breath, only part of the alveolar air is replaced by fresh atmospheric air.
• Second: Oxygen (O₂) is continuously absorbed from the alveoli into the pulmonary blood.
• Third: Carbon dioxide (CO₂) is continuously diffusing from the pulmonary blood into the alveoli.
• Fourth: The dry atmospheric air becomes humidified as it passes through the respiratory tract before reaching the alveoli.

KEY CONCEPT

• Alveolar air is different from atmospheric air.
• The four main reasons are:
  • Only partial replacement of alveolar air with each breath.
  • Continuous absorption of O₂ into the blood.
  • Continuous diffusion of CO₂ from blood into the alveoli.
  • Humidification of inspired air before it reaches the alveoli.

Air Is Humidified in the Respiratory Passages

📖 Table Mentioned: Table 40.1

• Atmospheric air is composed mainly of nitrogen (N₂) and oxygen (O₂).
• Atmospheric air normally contains almost no carbon dioxide (CO₂) and very little water vapor.
• As soon as atmospheric air enters the respiratory passages, it comes in contact with the moist fluid covering the respiratory surfaces.
• Before reaching the alveoli, the inspired air becomes almost completely humidified.
• At the normal body temperature of 37°C, the partial pressure of water vapor (PH₂O) is 47 mm Hg.
• Therefore, the partial pressure of water vapor in alveolar air is always 47 mm Hg.
• The total pressure inside the alveoli remains equal to atmospheric pressure (760 mm Hg at sea level).
• Since the total pressure cannot increase above 760 mm Hg, the added water vapor occupies part of this total pressure.
• As a result, the partial pressures of the other gases decrease (become diluted).

Effect of Humidification

• Oxygen (O₂) partial pressure:
  • Atmospheric air = 159 mm Hg
  • Humidified air = 149 mm Hg
• Nitrogen (N₂) partial pressure:
  • Atmospheric air = 597 mm Hg
  • Humidified air = 563 mm Hg

KEY CONCEPT

• Inspired air becomes almost completely humidified before reaching the alveoli.
• PH₂O at 37°C = 47 mm Hg.
• Water vapor dilutes the partial pressures of oxygen and nitrogen because the total alveolar pressure remains 760 mm Hg.
• Humidification decreases O₂ from 159 → 149 mm Hg and N₂ from 597 → 563 mm Hg.

Alveolar Air Is Slowly Renewed By Atmospheric Air

📖 Figures Mentioned: Figure 40.2 and Figure 40.3
📖 Table Mentioned: Table 40.1

• The functional residual capacity (FRC) is the volume of air remaining in the lungs after a normal expiration.
• In an average adult man, the FRC is about 2300 mL.
• During a normal inspiration, only 350 mL of fresh atmospheric air reaches the alveoli.
• During normal expiration, the same 350 mL of old alveolar air leaves the lungs.
• Therefore, only about one-seventh (350 mL out of 2300 mL) of the alveolar air is replaced with each normal breath.
• Because only a small portion is replaced each time, many breaths are needed to replace most of the alveolar air.
• Figure 40.2 shows that alveolar air is renewed slowly.
• Even after 16 breaths, some of the original gas still remains inside the alveoli.
• Figure 40.3 shows how quickly excess gas is removed from the alveoli at different ventilation rates.
• With normal alveolar ventilation, about 50% of the excess gas is removed in 17 seconds.
• If alveolar ventilation is half of normal, 50% of the excess gas is removed in 34 seconds.
• If alveolar ventilation is twice normal, 50% of the excess gas is removed in about 8 seconds.

KEY CONCEPT

• FRC = 2300 mL in an average adult man.
• Only 350 mL of fresh air enters the alveoli with each normal breath.
• Only 1/7 of alveolar air is replaced per breath, so alveolar air is renewed slowly.
• Higher alveolar ventilation removes gases faster, while lower ventilation removes gases more slowly.
• Half of the excess gas is removed in:
  • 17 seconds → Normal ventilation
  • 34 seconds → Half-normal ventilation
  • 8 seconds → Double-normal ventilation

Figure 40.2 – Expiration of a Gas From an Alveolus With Successive Breaths

Super Easy Concept

What does this figure show?

This figure explains why alveolar air is replaced slowly, not all at once.

Each red dot = gas molecule (air inside the alveolus).

Step-by-Step Understanding

Before Breathing

• The alveolus is completely filled with gas molecules.

🫁 Think of it as a balloon full of air.

After 1st Breath

• Only some old gas leaves.
• Fresh air enters and mixes with the remaining old air.

➡️ Most old gas is still present.

After 2nd Breath

• More old gas leaves.
• More fresh air enters.

➡️ But a lot of old gas still remains.

After 3rd & 4th Breaths

• Old gas continues to decrease gradually.
• Fresh air continues to replace it.

➡️ Replacement is slow and gradual.

After 8th Breath

• Only a small amount of the original gas remains.

After 12th Breath

• Very little of the original gas is left.

After 16th Breath

• Almost all of the original gas has been replaced.

✅ The alveolus now contains mostly fresh air, but this happened gradually over many breaths.

Why Doesn’t All the Air Leave in One Breath?

Because after a normal expiration:

• About 2300 mL of air remains in the lungs (Functional Residual Capacity, FRC).
• During each normal breath, only about 350 mL of fresh air reaches the alveoli.

So,

350 mL is much smaller than 2300 mL.

➡️ Therefore, each breath replaces only a small portion of alveolar air.

Simple Analogy

Imagine a bucket containing blue-colored water.

Instead of emptying the bucket completely:

• Remove only one cup of blue water.
• Add one cup of clear water.
• Mix it.

Repeat this many times.

The water becomes clearer gradually, not instantly.

🫁 Alveolar air behaves in exactly the same way.

Why Is Slow Replacement Important?

If alveolar air were replaced completely with every breath:

• Oxygen level would rise and fall suddenly.
• Carbon dioxide level would change abruptly.

Instead, slow replacement:

• Keeps oxygen levels stable
• Keeps carbon dioxide levels stable
• Allows continuous gas exchange, even between breaths

Exam Concept (One Line)

Alveolar air is renewed gradually because only a small amount of fresh air enters the alveoli with each normal breath while a large volume of air remains in the lungs (functional residual capacity).

Ultra-Short Revision

• 🫁 Alveolus always contains residual air
• 🌬️ Each breath replaces only a small part
• 🔄 Old and fresh air mix together
• ⏳ Complete replacement requires many breaths (about 16 in this illustration)
• ✅ This maintains stable O₂ and CO₂ levels for continuous gas exchange.

This graph (Guyton Physiology Fig. 40.3) is one of the most important concepts in respiratory physiology. It explains how fast an unwanted (excess) gas is washed out from the alveoli at different rates of alveolar ventilation.

Figure 40.3: Rate of Removal of Excess Gas from Alveoli

Step 1: Understand the Axes First

Y-Axis (Vertical)

Concentration of Gas (% of Original Concentration)

• At the beginning = 100%
• Means all excess gas is still present.
• As time passes, gas leaves the alveoli.
• Therefore concentration decreases.

Example

Suppose a patient inhales 100 molecules of anesthetic gas.

Time	Gas Remaining
Beginning	100%
Later	80%
Later	50%
Later	20%
End	Almost 0%

So,

Higher point = More gas remaining

Lower point = Less gas remaining

X-Axis (Horizontal)

Time (Seconds)

Shows how much time has passed.

Starts at

0 sec → 10 sec → 20 sec → 30 sec → 40 sec → 50 sec → 60 sec

As time increases,
the lungs continue removing excess gas.

Why Does the Curve Start at 100%?

At time zero,

The lungs have 100% of the excess gas.

Nothing has been removed yet.

So every curve begins at

100%

Why Do All Curves Go Down?

Because the lungs are constantly removing gas.

Each breath replaces old alveolar air with fresh air.

Old gas leaves.
Fresh air enters.

Therefore,

Gas concentration continuously falls.

Why Are the Curves Curved Instead of Straight?

This is the most important concept.

Imagine a bucket containing 100 marbles.

Each minute you remove 20% of the marbles remaining, not a fixed number.

First minute

100 → remove 20

Left = 80

Second minute

Remove 20% of 80

Remove 16

Left = 64

Third minute

Remove 20% of 64

Remove about 13

Left = 51

Notice:

At first,
gas disappears very quickly.

Later,
less gas remains,
so removal becomes slower.

Therefore,

The graph becomes a curve, not a straight line.

This is called exponential decay (washout).

There Are Three Different Curves

Each curve represents a different amount of alveolar ventilation.

① Middle Red Line = Normal Alveolar Ventilation

This is the normal healthy person’s breathing.

Normal breathing removes gas at a normal rate.

What happens?

0 sec

100%

↓

10 sec

Around 60%

↓

20 sec

Around 40%

↓

40 sec

Around 20%

↓

60 sec

Around 10%

Gas gradually disappears.

Concept

Normal breathing removes excess gas steadily.

Neither very fast nor very slow.

② Upper Blue Dashed Line = Half-Normal Alveolar Ventilation

This means

The person is breathing only half as much as normal.

Examples

• Respiratory depression
• Opioid overdose
• Sleeping deeply
• COPD
• Neuromuscular weakness
• Severe chest pain causing shallow breathing

What happens?

Fresh air enters slowly.

Old gas remains inside.

Therefore,

Gas removal becomes slow.

Observe the graph.

After 20 seconds,

Normal ventilation

≈40%

Half ventilation

≈60%

Much more gas is still inside.

Even after 60 seconds,

Nearly 30% of gas remains.

Easy Memory

Small ventilation

↓

Less fresh air

↓

Less washing

↓

Gas stays longer

Think of washing dirty clothes.

Using little water,

Dirt stays.

Exactly the same.

③ Lower Blue Dashed Line = Double-Normal Alveolar Ventilation

Now the person is breathing twice as much as normal.

Examples

Fresh air enters rapidly.

Old gas leaves rapidly.

Gas concentration falls very quickly.

Observe the graph.

Within about

20 seconds,

Only around 15–20% remains.

By

50–60 seconds,

Almost all gas has disappeared.

Easy Memory

Large ventilation

↓

More fresh air

↓

Better washing

↓

Gas disappears quickly

Imagine cleaning a dirty room.

One cleaner

↓

Room cleans slowly.

Five cleaners

↓

Room becomes clean rapidly.

Compare All Three Lines Together

Curve	Breathing	Gas Removal	Gas Remaining After 60 sec
Upper Blue	Half normal	Slowest	Highest (~30%)
Red	Normal	Moderate	Moderate (~10%)
Lower Blue	Double normal	Fastest	Almost 0%

Why Does More Ventilation Remove Gas Faster?

Every breath replaces some alveolar air.

Suppose

Normal breathing

Removes 350 mL old air each breath.

If breathing doubles,

Twice as much old air leaves every minute.

Therefore,

Excess gas is washed away much faster.

Clinical Correlation

During General Anesthesia

The anesthetic gas must leave the lungs after surgery.

If the patient breathes deeply,

Anesthetic leaves faster.

Recovery is quicker.

COPD Patient

Ventilation is reduced.

Gas removal becomes slow.

CO₂ accumulates.

Recovery is slower.

Exercise

Breathing increases.

Extra CO₂ produced by muscles is removed rapidly.

Hyperventilation

Extra CO₂ is washed out quickly.

Blood CO₂ falls.

This can cause dizziness and tingling due to respiratory alkalosis.

The Main Physiological Principle

The rate of removal (washout) of gas from the alveoli is directly proportional to alveolar ventilation.

• Higher alveolar ventilation → Faster gas removal
• Normal alveolar ventilation → Normal gas removal
• Lower alveolar ventilation → Slower gas removal

Super Easy Exam Memory Trick

Imagine three rooms filled with smoke:

• Room 1 (Half ventilation): Small fan → Smoke leaves slowly → Smoke stays longer.
• Room 2 (Normal ventilation): Normal fan → Smoke leaves at a normal rate.
• Room 3 (Double ventilation): Powerful fan → Smoke disappears very quickly.

Replace:

• Smoke = Excess gas in alveoli
• Fan = Alveolar ventilation

The stronger the “fan” (ventilation), the faster the excess gas is washed out of the alveoli. This is exactly what each curve in Figure 40.3 demonstrates.

Slow Replacement of Alveolar Air Helps Stabilize Respiratory Control

• Alveolar air is replaced slowly, not all at once.
• This slow replacement helps keep breathing under stable control.
• It prevents sudden changes in the levels of oxygen (O₂) and carbon dioxide (CO₂) in the blood.
• As a result, the respiratory control system works more smoothly and steadily.
• If breathing stops for a short time, slow air replacement helps reduce sudden changes in:
  • Oxygen (O₂) levels
  • Carbon dioxide (CO₂) levels
  • Blood pH (acid-base balance)
• This helps protect the body’s tissues from large fluctuations in gases and pH.

KEY CONCEPT

• Slow replacement of alveolar air acts as a buffer, keeping blood O₂, CO₂, and pH more stable and making respiratory control smoother and more stable.

Oxygen Concentration and Partial Pressure in Alveoli

• Oxygen (O₂) is continuously moving from the alveoli into the blood.
• At the same time, fresh oxygen is continuously entering the alveoli during breathing.
• If the blood absorbs oxygen more quickly, the oxygen concentration in the alveoli decreases.
• If more fresh oxygen enters the alveoli through breathing, the oxygen concentration in the alveoli increases.
• Therefore, the oxygen concentration and oxygen partial pressure (PO₂) in the alveoli depend on:
  • Rate of oxygen absorption into the blood
  • Rate of fresh oxygen entering the lungs through ventilation

Fig. 40.4

• Fig. 40.4 shows how alveolar ventilation and oxygen absorption into the blood affect alveolar PO₂.
• One curve shows oxygen absorption at 250 mL/min.
• The other curve shows oxygen absorption at 1000 mL/min.
• At a normal ventilation rate of 4.2 L/min and an oxygen consumption of 250 mL/min, the normal operating point is Point A.
• During moderate exercise, oxygen absorption increases to 1000 mL/min.
• To keep alveolar PO₂ at the normal value of 104 mm Hg, alveolar ventilation must increase 4 times.
• Even a very large increase in alveolar ventilation cannot raise alveolar PO₂ above 149 mm Hg when breathing normal air at sea level.
• This is because 149 mm Hg is the highest possible PO₂ in humidified air at sea level.
• If a person breathes oxygen-rich gas with a PO₂ higher than 149 mm Hg, alveolar PO₂ can rise closer to those higher values when ventilation is high.

KEY CONCEPT

• Alveolar PO₂ is controlled by the balance between oxygen entering the alveoli through ventilation and oxygen leaving the alveoli to enter the blood. More oxygen absorption lowers alveolar PO₂, while increased ventilation raises it.

This is one of the highest-yield physiology graphs from Guyton Physiology (Fig. 40.4). It explains how alveolar ventilation affects alveolar oxygen partial pressure (PAO₂) and why oxygen consumption changes the shape of the curve.

Let’s understand every axis, line, point, and concept in the easiest way.

Figure 40.4: Effect of Alveolar Ventilation on Alveolar PO₂

Step 1: Understand the Axes

X-Axis (Horizontal)

Alveolar Ventilation (L/min)

This means how much fresh air reaches the alveoli every minute.

Examples:

• 0 L/min = No breathing
• 5 L/min = Normal alveolar ventilation
• 20 L/min = Deep/rapid breathing
• 40 L/min = Maximum ventilation

👉 As you move to the right, ventilation increases.

Y-Axis (Vertical)

Alveolar Partial Pressure of Oxygen (PAO₂) (mmHg)

This tells us how much oxygen is present inside the alveoli.

Higher value = More oxygen available for diffusion into blood.

Lower value = Less oxygen available.

Why Does the Graph Start at (0,0)?

At 0 L/min, there is no breathing.

No fresh oxygen enters the lungs.

Meanwhile, blood continues to absorb oxygen from the alveoli.

Eventually:

• Alveolar oxygen becomes 0 mmHg.
• Therefore, the graph starts at 0,0.

What Do the Two Curves Represent?

The two curves show different rates of oxygen consumption by the body.

🔴 Red Curve = Oxygen Consumption = 250 mL O₂/min

This is the normal resting oxygen consumption of a healthy adult.

At rest:

• Body needs about 250 mL oxygen per minute.
• Blood removes oxygen from alveoli at this rate.

This is the normal physiological condition.

🔵 Blue Dashed Curve = Oxygen Consumption = 1000 mL O₂/min

This represents very high oxygen consumption, such as:

• Heavy exercise
• Running
• Severe fever
• Hyperthyroidism
• Strenuous physical work

Here, tissues extract oxygen from the blood four times faster than at rest.

Understanding the Red Curve (250 mL/min)

Imagine you’re filling a bucket with water while someone is taking water out slowly.

• Fresh oxygen enters through breathing.
• Blood removes oxygen at 250 mL/min.

As ventilation increases:

• More fresh oxygen enters.
• PAO₂ rises rapidly.

Initially, even a small increase in ventilation causes a big rise in PAO₂.

Later, the curve flattens because PAO₂ is approaching its maximum possible value.

Why Does the Red Curve Flatten?

Air entering the lungs contains oxygen with a PO₂ of about 149 mmHg (humidified inspired air).

Alveolar PO₂ cannot exceed the oxygen pressure of inspired air.

So no matter how much you hyperventilate, PAO₂ approaches this limit but cannot go beyond it.

This is why the graph becomes nearly horizontal.

Dashed Horizontal Line at ~149 mmHg

Upper limit at maximum ventilation

This represents the highest possible alveolar PO₂.

Even with extremely fast breathing:

• You cannot exceed inspired oxygen pressure.
• Therefore, the curve approaches this ceiling.

Think of it like filling a glass:

Once full, adding more water won’t increase the level.

Understanding the Blue Dashed Curve (1000 mL/min)

Now imagine the body is exercising.

Blood removes oxygen four times faster.

Fresh oxygen enters, but oxygen is also being consumed much more rapidly.

Therefore:

• PAO₂ stays lower at the same ventilation.

Example:

At 10 L/min ventilation:

• Red curve ≈ 125 mmHg.
• Blue curve ≈ 70 mmHg.

Same breathing, but much more oxygen is being used.

Why Is the Blue Curve Lower?

Because oxygen is disappearing from the alveoli faster.

It’s like pouring water into a bucket while someone is draining it much faster.

Even if you pour quickly, the level stays lower.

Point A (Black Dot)

This is the normal operating point.

At Point A:

• Alveolar ventilation ≈ 4–5 L/min.
• Oxygen consumption = 250 mL/min.
• PAO₂ ≈ 104 mmHg.

This represents a healthy person:

• Breathing normally.
• Resting.
• Normal metabolism.

This is the body’s usual state.

Dashed Horizontal Line at ~104 mmHg

Normal alveolar PO₂

This is the normal oxygen pressure inside alveoli under resting conditions.

Why not 149 mmHg?

Because oxygen is continuously leaving the alveoli and entering the blood.

So alveolar PO₂ is always lower than inspired PO₂.

Why Does Increasing Ventilation Raise PAO₂?

Every breath brings fresh oxygen into the alveoli.

More ventilation means:

• More fresh oxygen enters.
• Oxygen removed by blood is replaced faster.
• PAO₂ increases.

Why Doesn’t PAO₂ Increase Forever?

Fresh inspired air contains a limited amount of oxygen.

Its maximum PO₂ is about 149 mmHg.

You cannot increase alveolar PO₂ above the oxygen content of inspired air (unless you breathe oxygen-enriched gas).

Compare the Two Curves

Feature	🔴 Red Curve	🔵 Blue Curve
Oxygen consumption	250 mL/min	1000 mL/min
Physiological state	Rest	Heavy exercise
Oxygen removed from alveoli	Normal	Very high
PAO₂ at the same ventilation	Higher	Lower
Ventilation needed to reach PAO₂ ≈104 mmHg	~4–5 L/min	~18–20 L/min

Everyday Analogy

Imagine a water tank:

• Tap = Breathing (alveolar ventilation).
• Drain = Oxygen uptake by blood.

Situation 1 (Red Curve)

The drain is small.

The tank fills easily.

Water level (PAO₂) rises quickly.

Situation 2 (Blue Curve)

The drain is very large.

Water leaves rapidly.

You must open the tap much more to maintain the same water level.

This is exactly what happens during heavy exercise.

Clinical Correlation

1. Exercise

During exercise:

• Oxygen consumption increases to around 1000 mL/min or more.
• If ventilation also increases appropriately, PAO₂ remains near normal.
• If ventilation fails to increase, PAO₂ falls.

2. Respiratory Depression

If ventilation decreases:

• Less oxygen enters the alveoli.
• PAO₂ falls.
• Blood oxygen decreases (hypoxemia).

3. High Metabolic States

In conditions like:

• Fever
• Hyperthyroidism
• Sepsis

Oxygen consumption increases.

Without increased ventilation, alveolar PO₂ decreases.

High-Yield MBBS Exam Points

• Normal oxygen consumption at rest = 250 mL/min.
• Normal alveolar ventilation = about 4–5 L/min.
• Normal alveolar PO₂ ≈ 104 mmHg (Point A).
• Maximum possible alveolar PO₂ ≈ 149 mmHg (breathing room air).
• Increasing alveolar ventilation raises PAO₂.
• Increasing oxygen consumption lowers PAO₂ unless ventilation also increases.

Super Easy Memory Trick

Think of the alveoli as a water tank:

• 🚰 Tap = Alveolar ventilation (fresh oxygen entering).
• 🚿 Drain = Oxygen uptake by blood.
• 💧 Water level = Alveolar PO₂.
• Open the tap more (↑ ventilation) → Water level rises (↑ PAO₂).
• Open the drain more (↑ oxygen consumption) → Water level falls (↓ PAO₂).
• To keep the water level normal during exercise, you must open the tap wider—this is why ventilation increases during exercise.

CO₂ Concentration and Partial Pressure in Alveoli

• Carbon dioxide (CO₂) is continuously produced by the body’s tissues.
• CO₂ is carried by the blood to the alveoli.
• CO₂ is continuously removed from the alveoli during ventilation (breathing).
• Under normal steady conditions:
  • CO₂ produced by the tissues = CO₂ removed through the lungs.

Fig. 40.5

• Fig. 40.5 shows how alveolar ventilation and CO₂ excretion affect alveolar PCO₂.
• One curve represents a normal CO₂ excretion rate of 200 mL/min.
• The other curve represents a higher CO₂ excretion rate of 800 mL/min.
• At a normal alveolar ventilation of 4.2 L/min, the normal operating point is Point A.
• At Point A, the normal alveolar PCO₂ is 40 mm Hg.
• If CO₂ production and excretion increase from 200 mL/min to 800 mL/min (4 times higher), alveolar PCO₂ also increases proportionally.
• If alveolar ventilation increases, alveolar PCO₂ decreases.
• If alveolar ventilation decreases, alveolar PCO₂ increases.
• Therefore, the concentrations and partial pressures of both O₂ and CO₂ in the alveoli depend on:
  • Rate of gas absorption or excretion
  • Amount of alveolar ventilation

KEY CONCEPT

• Alveolar PCO₂ is directly proportional to CO₂ production and inversely proportional to alveolar ventilation. More CO₂ production raises PCO₂, while more ventilation lowers PCO₂.

This is Figure 40.5 from Guyton Physiology, and it is the opposite concept of Figure 40.4.

• Figure 40.4: More ventilation → Higher PO₂
• Figure 40.5: More ventilation → Lower PCO₂

This is one of the most frequently tested MBBS physiology concepts.

Figure 40.5: Effect of Alveolar Ventilation on Alveolar PCO₂

The One-Line Concept

Alveolar PCO₂ is directly proportional to CO₂ production and inversely proportional to alveolar ventilation.

Mathematically:$$\boxed{\text{Alveolar PCO₂} \propto \frac{\text{CO₂ production}}{\text{Alveolar ventilation}}}$$Alveolar PCO₂∝Alveolar ventilationCO₂ production​​

This means:

• ↑ CO₂ production → ↑ PCO₂
• ↑ Alveolar ventilation → ↓ PCO₂

Step 1: Understand the Axes

X-Axis (Horizontal)

Alveolar Ventilation (L/min)

This means:

Fresh air reaching the alveoli every minute.

Examples

• 0 L/min = No breathing
• 5 L/min = Normal breathing
• 20 L/min = Deep breathing
• 40 L/min = Maximum ventilation

👉 Moving right means more breathing.

Y-Axis (Vertical)

Alveolar Partial Pressure of CO₂ (PACO₂)

This tells us

How much carbon dioxide is present inside the alveoli.

Higher value

↓

More CO₂ trapped

Lower value

↓

Less CO₂ remaining

Why Does the Graph Start Very High?

Imagine

You suddenly stop breathing.

No fresh air enters.

No CO₂ leaves.

But the body keeps producing CO₂.

Blood continuously delivers CO₂ into the alveoli.

Therefore

CO₂ accumulates rapidly.

Hence,

PCO₂ becomes very high.

Why Do Both Curves Go Down?

As ventilation increases,

Fresh air enters.

Old CO₂-rich air leaves.

Therefore,

CO₂ concentration inside alveoli decreases.

More ventilation

↓

More CO₂ washed out

↓

Lower alveolar PCO₂

Understanding the Two Curves

The curves represent two different rates of CO₂ production by the body.

🔴 Red Curve = CO₂ Production = 200 mL/min

This is the normal resting CO₂ production.

A healthy adult produces approximately:

200 mL CO₂ per minute

This is the normal resting condition.

What Happens?

At low ventilation

↓

CO₂ accumulates.

As ventilation increases

↓

CO₂ is removed rapidly.

Eventually,

PCO₂ becomes quite low.

Observe the graph.

At

5 L/min ventilation

↓

PCO₂ ≈40 mmHg

Normal value.

At

20–40 L/min

↓

PCO₂ becomes very low

Around 10–15 mmHg.

Easy Concept

Normal CO₂ production

Normal breathing

=

Normal alveolar PCO₂

🔵 Blue Dashed Curve = CO₂ Production = 800 mL/min

This represents

Very high metabolic activity.

Examples

• Heavy exercise
• Running
• Fever
• Hyperthyroidism
• Severe muscle activity

The body now produces

800 mL CO₂/min

which is

4 times normal.

What Happens?

Blood delivers much more CO₂ into the alveoli.

Even if breathing is increased,

CO₂ is entering the alveoli very rapidly.

Therefore

PCO₂ stays higher.

Observe the graph.

At

10 L/min ventilation

Red curve

≈15 mmHg

Blue curve

≈70 mmHg

Same ventilation

↓

Much higher CO₂ production

↓

Higher alveolar PCO₂.

Why Is the Blue Curve Higher?

Imagine

You have

A room filling with smoke.

One small fire

↓

Little smoke.

Large fire

↓

Huge amount of smoke.

Even with the same fan,

The room stays smokier.

Exactly the same.

The fire

=

CO₂ production

The fan

=

Ventilation

Point A (Black Dot)

Point A represents

The normal operating point.

At Point A

Alveolar ventilation

≈4–5 L/min

CO₂ production

≈200 mL/min

Alveolar PCO₂

≈40 mmHg

This is a healthy resting adult.

Dashed Horizontal Line (40 mmHg)

This line represents

Normal alveolar PCO₂

Normal value

≈40 mmHg

Remember

Alveolar PCO₂

≈

Arterial PCO₂

≈40 mmHg

This is a favorite MBBS viva question.

Why Does More Ventilation Lower CO₂?

Every breath removes CO₂.

If breathing doubles,

Twice as much CO₂ leaves the lungs every minute.

Therefore

CO₂ cannot accumulate.

Hence

PCO₂ falls.

Why Is the Curve So Steep Initially?

Look carefully.

Going from

2 L/min

↓

5 L/min

causes a huge fall in PCO₂.

Later,

Increasing ventilation

from

30

↓

40 L/min

causes only a small fall.

Why?

Because most CO₂ has already been washed out.

Removing the remaining small amount makes little difference.

Compare Both Curves

Feature	🔴 Red Curve	🔵 Blue Curve
CO₂ production	200 mL/min	800 mL/min
Physiological state	Rest	Heavy exercise
CO₂ entering alveoli	Normal	Very high
Alveolar PCO₂ at same ventilation	Lower	Higher
Ventilation needed to maintain PCO₂ ≈40 mmHg	~4–5 L/min	~18–20 L/min

Compare Figure 40.4 and Figure 40.5

Feature	Figure 40.4 (PO₂)	Figure 40.5 (PCO₂)
Gas	Oxygen	Carbon dioxide
Increasing ventilation	↑ PO₂	↓ PCO₂
High metabolism	↓ PO₂	↑ PCO₂
Normal value	PAO₂ ≈104 mmHg	PACO₂ ≈40 mmHg
Curve shape	Rises then plateaus	Falls rapidly then plateaus

Clinical Correlation

1. Hyperventilation

Examples

• Anxiety
• Panic attack
• Mechanical overventilation

Effects

↑ Ventilation

↓

More CO₂ removed

↓

↓ PACO₂

↓

Respiratory alkalosis

Symptoms

• Dizziness
• Tingling
• Lightheadedness

2. Hypoventilation

Examples

• COPD
• Opioid overdose
• Neuromuscular disease

Effects

↓

Less CO₂ removal

↓

↑ PACO₂

↓

Respiratory acidosis

3. Exercise

During exercise

CO₂ production increases greatly.

To maintain normal PACO₂,

Ventilation also increases proportionally.

This is why healthy people exercising hard usually keep their arterial and alveolar PCO₂ close to 40 mmHg despite producing much more CO₂.

High-Yield MBBS Exam Points

• Normal CO₂ production = 200 mL/min.
• Heavy exercise can increase CO₂ production to about 800 mL/min or more.
• Normal alveolar ventilation = about 4–5 L/min.
• Normal alveolar PCO₂ ≈ 40 mmHg (Point A).
• Increasing alveolar ventilation lowers alveolar PCO₂.
• Increasing CO₂ production raises alveolar PCO₂ unless ventilation increases proportionally.
• Alveolar PCO₂ is approximately equal to arterial PCO₂ under normal conditions.

Super Easy Memory Trick

Imagine the alveoli as a room:

• 🔥 Fire = Body producing CO₂
• 🌬️ Exhaust fan = Alveolar ventilation
• 🌫️ Smoke = CO₂ inside the alveoli (PACO₂)
• Small fire + normal fan → Little smoke (normal PACO₂ ≈ 40 mmHg).
• Big fire + same fan → Room fills with smoke (↑ PACO₂).
• Turn the fan faster (↑ ventilation) → Smoke is removed quickly (↓ PACO₂).

Final Rule to Never Forget

• Oxygen behaves like filling a tank: More ventilation → Higher PAO₂.
• Carbon dioxide behaves like emptying waste: More ventilation → Lower PACO₂.

This opposite relationship between PO₂ and PCO₂ with alveolar ventilation is the key physiological message of Figures 40.4 and 40.5.

Expired Air Is a Combination of Dead Space Air and Alveolar Air

• Expired air is made up of:
  • Dead space air
  • Alveolar air
• The final composition of expired air depends on:
  • The amount of dead space air
  • The amount of alveolar air

Fig. 40.6

• Fig. 40.6 shows how the O₂ and CO₂ partial pressures change during expiration.
• The first part of expired air comes from the respiratory passageways.
• This first part is dead space air.
• Dead space air has the same composition as humidified inspired air.
• As expiration continues, more alveolar air mixes with the dead space air.
• Gradually, all the dead space air is expelled.
• At the end of expiration, only alveolar air is expired.
• To collect a sample of alveolar air:
  • Ask the person to exhale forcefully.
  • Collect the last part of the expired air.
  • This ensures that the dead space air has already been removed.
• Normal expired air contains both dead space air and alveolar air.
• Therefore, its gas concentrations and partial pressures are between those of alveolar air and humidified atmospheric air.

KEY CONCEPT

• Expired air is a mixture of dead space air and alveolar air. Early expired air is mainly dead space air, while the last part of expiration is pure alveolar air.

This is Figure 40.6 from Guyton Physiology, and it explains why the composition of expired air changes during one normal expiration.

Core Concept:
Expired air is NOT pure alveolar air.
It is a mixture of dead space air and alveolar air.

This graph explains exactly which air comes out first, which comes out later, and why the PO₂ and PCO₂ change during expiration.

Step 1: Understand the Axes

X-Axis (Horizontal)

Air Expired (milliliters)

This shows how much air has come out of the lungs during one expiration.

Starts from

• 0 mL → Beginning of expiration
• 100 mL
• 200 mL
• 500 mL → End of expiration

👉 As you move to the right, more air has been exhaled.

Y-Axis (Vertical)

Partial Pressure (mmHg)

Shows the partial pressure of

• Oxygen (PO₂) (Red line)
• Carbon dioxide (PCO₂) (Blue line)

First Understand Where the Air Comes From

At the end of inspiration, the respiratory tract contains two different types of air.

Mouth
 │
Trachea
 │
Bronchi
 │
Bronchioles
 │
Alveoli

The air inside the lungs is divided into:

1. Conducting Airways (Dead Space)

Contains

Fresh inspired air

No gas exchange occurs here.

2. Alveoli

Contains

Alveolar air

Gas exchange has already occurred.

Therefore,

At the beginning of expiration,

Air does NOT come from alveoli first.

It comes from the conducting airways first.

This is the entire idea of the graph.

The Three Shaded Regions

The graph is divided into three regions, each representing a different type of expired air.

🟦 Region 1 (Dark Blue Shaded Area)

Dead Space Air

Approximately

0–150 mL

This is the first air that comes out during expiration.

Where does this air come from?

From

• Nose
• Pharynx
• Trachea
• Bronchi

These conducting airways do not exchange gases with blood.

Therefore, this air is almost identical to inspired air.Oxygen in Dead Space Air (Red Line)

Look at the red line.

It starts around

150 mmHg

Why?

Because dead space air is fresh atmospheric air.

Inspired humidified air has:

PO₂ ≈150 mmHg

So,

The first expired air contains a high oxygen concentration.

Carbon Dioxide in Dead Space Air (Blue Line)

Look at the blue line.

It is almost

0 mmHg

Why?

Because inspired air contains almost no CO₂.

No gas exchange occurred in dead space.

Therefore,

CO₂ remains almost zero.

Summary of Region 1

Gas	Value
PO₂	High (~150 mmHg)
PCO₂	Very low (~0 mmHg)

This air has not participated in gas exchange.

🟦 Region 2 (Light Blue Shaded Area)

Mixture of Dead Space Air + Alveolar Air

Approximately

150–250 mL

Now something important happens.

Dead space air has already left.

Alveolar air begins reaching the mouth.

But initially,

Both types of air mix together.

What Happens to PO₂? (Red Line)

Observe the red line.

It begins to fall.

Why?

Because

Dead space air

↓

High oxygen

mixes with

Alveolar air

↓

Lower oxygen

The mixture has an intermediate oxygen level.

Therefore,

PO₂ gradually decreases.

What Happens to PCO₂? (Blue Line)

Look carefully.

It begins rising.

Why?

Dead space air

↓

Almost no CO₂

mixes with

Alveolar air

↓

High CO₂

Therefore,

The mixed air has increasing CO₂.

Hence,

The blue curve rises.

Why Are These Curves Smooth?

Because mixing is gradual.

It is not like switching on a light.

Initially,

Mostly dead space air.

Then,

Increasing alveolar air.

Finally,

Pure alveolar air.

Therefore,

The change is gradual.

Summary of Region 2

Gas	What Happens?	Why?
PO₂	Falls gradually	More alveolar air enters the expired air
PCO₂	Rises gradually	Increasing amount of alveolar air contains more CO₂

⬜ Region 3 (White Area)

Pure Alveolar Air

Approximately

After 250 mL

Now

Almost all dead space air has already been expelled.

Only alveolar air remains.

Oxygen (Red Line)

Observe the graph.

It becomes flat around

100 mmHg

Why?

This is the normal alveolar PO₂.

Pure alveolar air has

PO₂ ≈100–104 mmHg

No more dead space air is mixing.

Therefore,

The value becomes constant.

Carbon Dioxide (Blue Line)

Observe the blue line.

It becomes flat around

40 mmHg

Why?

Pure alveolar air contains

PCO₂ ≈40 mmHg

Again,

No dead space air is left.

So the value remains constant.

Summary of Region 3

Gas	Value
PO₂	≈100 mmHg
PCO₂	≈40 mmHg

This represents true alveolar air.

Understanding the Red Line (PO₂)

Let’s follow it step by step.

Beginning

Dead space air

↓

PO₂ ≈150 mmHg

↓

Fresh inspired air

Middle

Mixing begins

↓

PO₂ falls gradually

End

Pure alveolar air

↓

PO₂ ≈100 mmHgnderstanding the Blue Line (PCO₂)

Beginning

Dead space air

↓

PCO₂ ≈0 mmHg

↓

Almost no CO₂

Middle

Mixing begins

↓

PCO₂ rises

End

Pure alveolar air

↓

PCO₂ ≈40 mmHg

Why Does Dead Space Air Come Out First?

Imagine a drinking straw attached to a balloon.

Mouth
  │
 Straw
  │
 Balloon

• Straw = Conducting airways (dead space)
• Balloon = Alveoli

When you squeeze the balloon:

• The air already inside the straw comes out first.
• Only after the straw empties does balloon air come out.

Exactly the same happens in the lungs.

Why Is This Clinically Important?

If you collect the very first expired air, it does not represent alveolar gas.

To estimate alveolar gases accurately, clinicians analyze the end-expiratory air (end-tidal gas), because it comes from the alveoli and reflects:

• End-tidal CO₂ (ETCO₂) ≈ alveolar PCO₂.
• End-expiratory O₂ ≈ alveolar PO₂.

Complete Summary Table

Region	Air Coming Out	PO₂	PCO₂	Reason
1. Dark blue	Dead space air only	≈150 mmHg	≈0 mmHg	Fresh inspired air, no gas exchange
2. Light blue	Mixture of dead space + alveolar air	Falls from 150 → 100 mmHg	Rises from 0 → 40 mmHg	Progressive mixing of the two air types
3. White	Pure alveolar air	≈100 mmHg	≈40 mmHg	Air has fully participated in gas exchange

High-Yield MBBS Viva Points

• Expired air is a mixture of dead space air and alveolar air.
• The first expired air comes from the anatomical dead space.
• Dead space air has PO₂ ≈150 mmHg and PCO₂ ≈0 mmHg because no gas exchange occurs there.
• During the middle of expiration, dead space air mixes with alveolar air, producing gradual changes in PO₂ and PCO₂.
• The last part of expiration is pure alveolar air with PO₂ ≈100 mmHg and PCO₂ ≈40 mmHg.
• End-expiratory (end-tidal) gas best represents alveolar gas composition.

Super Easy Memory Trick

Imagine a pipe connected to a water tank:

• Pipe = Dead space (conducting airways)
• Water tank = Alveoli

When you open the valve:

1. Water already in the pipe comes out first → Dead space air (high O₂, almost no CO₂).
2. Pipe water mixes with tank water → Mixed air (O₂ falls, CO₂ rises).
3. Only tank water comes out → Pure alveolar air (PO₂ ≈100 mmHg, PCO₂ ≈40 mmHg).

Think: Pipe first, then mixture, then tank — this sequence exactly matches the three shaded regions in Figure 40.6.