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# Oxygen at the tissue level: interstitial and cellular PO₂

- Mechanism
- Exam priority: medium

Oxygen steps down from blood to tissue fluid to cells. Mitochondria need very little, so cells usually burn O₂ as fast as they need energy.

Updated Nov 13, 2026

Also called: Tissue PO₂, Critical mitochondrial PO₂, Supply-dependent O₂ consumption

## Key points

- Interstitial PO₂ ≈ 40 mmHg and intracellular PO₂ ≈ 5–40 mmHg (average about 23); mitochondria need only about 1–3 mmHg.
- More blood flow raises tissue PO₂ (never above arterial PO₂); more metabolism lowers it.
- Hemoglobin buffers tissue PO₂: its steep unloading curve keeps tissue PO₂ in a narrow range despite wide changes in alveolar PO₂.
- Normally O₂ use is ADP-limited: it follows the cell's energy demand, not the O₂ supply.
- Below a critical O₂ delivery, consumption becomes supply-dependent: extraction is maxed out, ATP falls and lactate rises.

## What it is

Oxygen leaves capillaries by diffusion, down a pressure gradient from blood (about 95 mmHg arterial) to interstitial fluid (about 40 mmHg) to cell interior (about 5–40 mmHg). Tissue PO₂ is a balance between delivery by blood flow and use by metabolism. Because mitochondria work at a PO₂ of only a few mmHg, O₂ use is normally set by energy demand (ADP), and only becomes limited by supply when delivery falls very low.

## How it works, step by step

- Arterial blood enters capillaries at PO₂ ≈ 95 mmHg; O₂ diffuses out toward the lower interstitial PO₂.
- By the venous end, capillary PO₂ has fallen to about 40 mmHg, close to interstitial PO₂.
- From interstitial fluid O₂ diffuses into cells, where its PO₂ falls further with distance from the capillary.
- Inside the cell, cytochrome c oxidase binds O₂ so avidly that the reaction runs at full speed above about 1 mmHg.
- So, with enough O₂, the rate of use depends on ADP: work makes ADP, ADP speeds oxidative phosphorylation.
- As tissue PO₂ falls, hemoglobin unloads more O₂ for a small drop in PO₂, which holds tissue PO₂ up.
- If delivery keeps falling (shock, severe anemia), extraction reaches its limit; mitochondrial PO₂ drops below critical and anaerobic glycolysis makes lactate.

### Oxygen–hemoglobin dissociation curve

**P50** 26.8 mmHg **Arterial blood** 97 % **Mixed venous blood** 75 % **O₂ given up to the tissues** 23 %

Normal curve. Tap a point (arterial, venous or P50) or move a control.

- Current curve
- Normal curve (pH 7.40 · 37 °C)
- Arterial blood (PO₂ 100)
- Mixed venous blood (PO₂ 40)
- O₂ given up to the tissues

Between 40 and 20 mmHg the curve is steep: a small fall in tissue PO₂ releases a lot of O₂.

## Equations

**O₂ consumption (Fick)**VO2 = Q × (CaO2 − CvO2)

**VO 2**
O₂ consumption, mL/min

**Q**
blood flow

**CaO 2 − CvO 2**
arteriovenous O₂ content difference

Whole body at rest ≈ 250 mL/min; flow and extraction trade off.

**O₂ extraction ratio**O2ER = VO2 / DO2 ≈ (SaO2 − SvO2) / SaO2

**DO 2**
O₂ delivery = Q × CaO₂

≈ 25% at rest; when it nears its maximum, use becomes supply-dependent.

## O₂ partial pressures along the path (approximate, at rest)

| Parameter | Value | Note |
| --- | --- | --- |
| Arterial blood | ≈ 95 mmHg | |
| Venous end of capillary | ≈ 40 mmHg | |
| Interstitial fluid | ≈ 40 mmHg | lower in active tissue |
| Inside cells | ≈ 5–40 mmHg | average ≈ 23 mmHg |
| Critical mitochondrial PO₂ | ≈ 1–3 mmHg | |
| Resting extraction ratio | ≈ 25% | |

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

## Regulation

- *+* **Higher blood flow**: Raises tissue PO₂, up to the arterial value.
- *−* **Higher metabolic rate**: Lowers tissue PO₂ and raises extraction.
- *+* **Right shift of the O₂–Hb curve (acid, CO₂, heat, 2,3-BPG)**: More O₂ unloaded at the same PO₂.
- *−* **Edema and longer diffusion distance**: Lowers PO₂ in cells far from capillaries.

## Clinical notes

- Rising lactate in sepsis or shock signals that some tissues have passed from ADP-limited to supply-limited O₂ use (or have impaired O₂ use).
- A low mixed venous saturation means tissues are extracting more because delivery is falling behind demand.
- Edema lengthens diffusion distance, one reason swollen tissue heals poorly.

## Memory aid

Mitochondria are sippers, not gulpers: they need only a few mmHg, and drink as fast as ADP orders.

## Test yourself

Think of the answer, then tap the question to see it.

## What normally limits the rate of O₂ use by cells when intracellular PO₂ is above a few mmHg?

The concentration of ADP: cells use O₂ in proportion to the energy they spend (ADP-limited), not in proportion to supply.

## What happens to tissue PO₂ when blood flow to a muscle doubles at constant metabolism?

It rises toward, but never above, arterial PO₂, because more O₂ arrives per minute than the same metabolism removes.

## How does hemoglobin act as a tissue O₂ buffer?

On the steep part of its curve, a small fall in tissue PO₂ releases a large amount of O₂, so tissue PO₂ stays in a narrow range even when supply or demand changes.

## Why does lactate rise when O₂ delivery falls below a critical level?

Extraction is already maximal, so mitochondrial PO₂ falls below the critical level, oxidative phosphorylation slows and cells turn to anaerobic glycolysis, making lactate.

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## Connections

## Related topics 4

- [Oxygen content, delivery and extraction](https://durgical.com/en/physiology/oxygen-content-delivery-and-extraction/)
- [Oxygen transport and the dissociation curve](https://durgical.com/en/physiology/oxygen-transport-and-the-dissociation-curve/)
- [Local and humoral control of blood flow](https://durgical.com/en/physiology/local-and-humoral-control-of-blood-flow/)
- [Exercise and training physiology](https://durgical.com/en/physiology/exercise-and-training-physiology/)

## Related conditions 3

- [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/)
- [Sepsis and septic shock](https://durgical.com/en/conditions/sepsis-and-septic-shock/)
- [Hypovolaemic shock](https://durgical.com/en/conditions/hypovolaemic-shock/)

## In Biochemistry 2

- [Cytochrome c oxidase (complex IV)](https://durgical.com/en/biochemistry/enzymes/cytochrome-c-oxidase/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [Lactic acidosis: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000391.htm) (MedlinePlus, US National Library of Medicine, 2025); [Lactate Test: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/lactic-acid-test/) (MedlinePlus, US National Library of Medicine, 2025); [Hypovolemia and Hypovolemic Shock](https://www.ncbi.nlm.nih.gov/books/NBK513297/) (StatPearls (NCBI Bookshelf), 2025).

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