What Happens When Tissues Do Not Receive Enough Oxygen? Hypoxia Explained
Hypoxia means that the tissues of the body are not getting enough oxygen to meet their needs. Without enough oxygen, cells cannot make the energy they need to work. If the shortage is short and mild, they can cope and recover, but a severe or long-lasting shortage can kill cells and damage organs, especially the brain and heart.
By Chris Morais, MSc, MPhil, PhD
Published
When tissues run short of oxygen, their cells lose most of their energy supply. They switch on a protein called HIF and fall back on breaking down sugar without oxygen, which makes lactic acid. A brief shortage can usually be undone. A severe or long shortage makes cells swell and burst, and can permanently harm the brain and heart.
- What Is Hypoxia?
- What Is the Difference Between Hypoxia and Hypoxemia?
- What Causes Hypoxia?
- How Do Cells Sense Low Oxygen?
- How Do Cells Make Energy When Oxygen Is Low?
- What Happens to Cells During Severe Oxygen Shortage?
- How Does the Body Respond to Low Oxygen?
- What Are the Signs of Hypoxia?
- Which Organs Are Most Sensitive to Low Oxygen?
- Frequently Asked Questions
What Is Hypoxia?
Hypoxia is when the tissues or organs of the body do not have enough oxygen[1]. More exactly, it is a mismatch between the amount of oxygen that reaches the cells and the amount they need[2].
Oxygen enters the body through the lungs. Red blood cells then carry it in the blood to every tissue. Inside each cell, the mitochondria, the cell's energy-making parts, use this oxygen to turn food into energy[3]. You can read more about these parts in What Is a Cell and How Does It Work?
Hypoxia can affect the whole body, as when a person cannot breathe properly. It can also affect one area, such as part of the heart when an artery is blocked. It can come on suddenly, or it can last a long time with milder symptoms[1]. Some tissues can cope with short dips in oxygen, but hypoxia that lasts can cause organ damage[1].
What Is the Difference Between Hypoxia and Hypoxemia?
Hypoxemia means low oxygen in the blood, while hypoxia means low oxygen in the body's tissues[1].
The two often go together. When the blood carries too little oxygen, the tissues cannot get enough either. Doctors call this hypoxemic hypoxia, and it is the most common type of hypoxia[1].
But hypoxia can also happen when the blood has plenty of oxygen. If that blood does not reach a tissue, or if the cells cannot use the oxygen that arrives, the tissue still runs short[1].
This difference shows up in testing. A pulse oximeter, a small sensor placed on a finger, and an arterial blood gas test, which uses blood taken from an artery, both measure oxygen in the blood[1]. A normal blood oxygen result therefore does not always mean that every tissue is getting enough oxygen.
What Causes Hypoxia?
Hypoxia is caused by anything that stops the blood from picking up enough oxygen, carrying it, delivering it to the tissues, or letting cells use it[1]. Doctors group these causes into four main types.
The table below shows the four types of hypoxia, with examples of each[1].
| Type | What goes wrong | Examples |
|---|---|---|
| Hypoxemic | The blood picks up too little oxygen | Lung diseases such as COPD, asthma and pneumonia; sleep apnea; medicines that slow breathing; high altitude |
| Anemic | Too few working red blood cells to carry oxygen | Anemia |
| Circulatory (ischemic) | Oxygen-rich blood does not reach the tissue | Heart failure, a blocked blood vessel, a blood clot |
| Histotoxic | Oxygen reaches the cells, but they cannot use it | Cyanide poisoning |
Circulatory hypoxia is closely linked to ischemia. Ischemia means that blood flow to a tissue is reduced or stopped. It is one cause of hypoxia, but the two words do not mean the same thing. Hypoxia is a shortage of oxygen, whatever the cause. Ischemia is a shortage of blood. The tissue loses its supply of sugar and other nutrients as well as oxygen, and waste is no longer carried away. For this reason, ischemia usually harms tissue faster than low oxygen alone.
How Do Cells Sense Low Oxygen?
Cells sense low oxygen through enzymes that need oxygen to work. When oxygen falls, these enzymes slow down, and a protein called HIF builds up and switches on genes that help the cell survive[2].
The oxygen-sensing enzymes are called prolyl hydroxylases, or PHDs for short. When oxygen levels are normal, PHDs attach a small chemical tag to HIF. This tag marks HIF for destruction, so the cell breaks it down[2].
When oxygen is low, PHDs work less well. Less of the tag is added, and HIF is no longer broken down[2]. It builds up and goes to work. This gives cells a quick, built-in way to tell when oxygen is running short.
What Is HIF?
HIF, short for hypoxia-inducible factor, is a protein that switches on genes when oxygen is low[2]. It is made of two parts, called alpha and beta. The best-studied form is HIF-1[2].
Some of the genes HIF switches on change how the cell makes energy. Two of them, called LDH-A and PDK1, steer the cell's sugar fuel away from the mitochondria and toward a pathway that does not need oxygen and that makes lactic acid[2]. The next section explains this pathway.
Cancer cells use the same HIF system to survive in the low-oxygen parts of a tumor. This is explained in What Is the Tumor Microenvironment and How Does It Help Cancer Grow?
How Do Cells Make Energy When Oxygen Is Low?
When oxygen is low, cells make energy by breaking down sugar without oxygen, which gives them far less energy than normal[3].
Cells run on a fuel molecule called ATP. To make it, a cell first splits glucose (sugar) into a smaller molecule called pyruvate. This step is called glycolysis. It takes place in the fluid of the cell and does not need oxygen[3]. Pyruvate then moves into the mitochondria. There, oxygen is needed at the final step. Without oxygen, this final step stops[3].
The difference in energy is large. With oxygen, a cell can make about 36 ATP from one glucose molecule. Glycolysis on its own gives a net gain of only 2[3]. That is about one-eighteenth as much energy.
This backup system works well only for short periods, from seconds to a few minutes[3]. Muscles use it during hard exercise, when they need energy faster than oxygen can arrive[3]. Red blood cells have no mitochondria, so they rely on it all the time[3].
Cells that need a lot of energy cannot last long on it. In heart muscle cells, glycolysis becomes the only real source of ATP within about 15 to 20 seconds of low oxygen, and it cannot meet their needs[2].
Why Does Lactic Acid Build Up?
Lactic acid builds up because, without oxygen, cells turn pyruvate into lactic acid so that glycolysis can keep going[3]. This step frees up a helper molecule that glycolysis needs in order to continue[3].
In a healthy body, lactic acid passes into the blood and travels to the liver. The liver turns it back into glucose[3]. This is why muscles can make lactic acid during hard exercise and then clear it.
When oxygen stays low, lactic acid collects inside the cells and makes them more acidic[2]. In heart muscle cells, this acid slows glycolysis itself after about 15 to 20 minutes, so even the backup energy supply begins to fail[2].
What Happens to Cells During Severe Oxygen Shortage?
During a severe oxygen shortage, cells run out of energy, take in water and swell, and, if oxygen does not return in time, break open and die[4]. The changes happen in a set order:
- Energy falls. Without oxygen, the cell's energy-making chain cannot make enough ATP[4].
- Pumps fail. Pumps in the cell's outer membrane use ATP to keep the right balance of salts inside and outside the cell. When ATP runs too low, these pumps stop working[4].
- The cell swells. Salt builds up inside the cell, and water follows it in. The cell swells, and small bubbles form on its surface[4].
- Calcium builds up. Calcium collects inside the cell and switches on enzymes that break down its membranes. This sets up a vicious circle in which damage leads to more damage[4]. Low oxygen can also produce harmful, reactive forms of oxygen[4].
- The cell bursts. The outer membrane breaks and the cell's contents spill out[4].
Whether a cell recovers depends on how severe the shortage is and how long it lasts[4]. Early swelling can be undone. If oxygen returns soon, the swelling can go down quickly and the cell can return to normal[4]. Heart muscle cells show how narrow this window can be. They stop contracting within 1 to 2 minutes of hypoxia, but they may not die for another 20 to 30 minutes[2].
If the shortage goes on, the cell reaches a point of no return, marked by severe swelling of its mitochondria[4]. After this point, the cell will die even if oxygen comes back[4]. This type of cell death is called necrosis. It is explained in What Happens When Cells and Tissues Are Damaged?
How Does the Body Respond to Low Oxygen?
The body responds to low oxygen by breathing faster, speeding up the heart, releasing more oxygen to the tissues and, over time, making more red blood cells[1],[5].
- Faster breathing and heartbeat. Fast breathing and a fast heart rate are among the common signs of hypoxia[1]. They bring more air into the lungs and move blood around the body faster.
- Releasing more oxygen. Red blood cells make more of a substance called BPG. It helps hemoglobin, the protein that carries oxygen, let go of its oxygen in the tissues[5].
- Making more red blood cells. Low oxygen in the tissues prompts the kidneys to release a hormone called erythropoietin (EPO). EPO raises the production of red blood cells over time[5].
- Changes inside cells. Cells switch on HIF and shift to making energy without oxygen, as described above[2].
These responses work best when low oxygen is mild and comes on slowly. The heart, for example, can cope with mild hypoxia, such as at high altitude, through these kinds of changes[2]. A sudden, severe shortage leaves no time to adapt.
How Does the Body Adapt to High Altitude?
The body adapts to high altitude by releasing more oxygen to its tissues, concentrating its blood and making more red blood cells. This process is called acclimatization[5].
Air at high altitude still contains 21% oxygen, but the air pressure is lower. As a result, less oxygen passes from the lungs into the blood[5]. At sea level, hemoglobin is about 98% full of oxygen. At 19,000 feet (about 5,800 meters), it is only about 67% full[5].
Even so, the tissues of a person at rest still get enough oxygen. This is because hemoglobin releases a larger share of the oxygen it carries when it reaches the tissues[5].
Over time, the body also makes several changes[5]:
- Red blood cells make more BPG, so more oxygen is released in the tissues.
- The kidneys make more urine. This lowers the amount of fluid in the blood, so the red blood cells become more concentrated.
- The kidneys release more EPO, so more red blood cells are made.
Going up too quickly can cause acute mountain sickness. It can occur from about 2,400 meters (8,000 feet) above sea level. Symptoms include nausea, vomiting, tiredness, lightheadedness, drowsiness, confusion, a faster pulse and nosebleeds[5]. Severe cases can lead to fluid build-up in the lungs or brain. Going down to a lower altitude is the only definite treatment, while climbing slowly and drinking enough fluids help prevent it[5].
What Are the Signs of Hypoxia?
Common signs of hypoxia are restlessness, headache, confusion, anxiety, a fast heart rate, fast breathing and shortness of breath[1]. Severe hypoxia can cause a slow heart rate, extreme restlessness and a bluish color of the skin, lips or nails, called cyanosis[1].
Signs depend on the cause and how quickly the oxygen level falls. Long-lasting hypoxia can cause milder symptoms[1]. Not every breathing problem causes a drop in oxygen[1].
Hypoxia can be life-threatening and needs prompt care[1]. Call your local emergency number or go to the nearest emergency department for severe shortness of breath, confusion, a fast heart rate or breathing rate, or bluish lips, nails or skin. Seek help at once if someone suddenly becomes confused, restless or less alert[1]. Home oxygen readers are not always accurate, so a normal reading should not be used to rule out emergency care[1].
Which Organs Are Most Sensitive to Low Oxygen?
The brain and heart are the organs most sensitive to low oxygen, and damage to them is particularly dangerous[1].
- Brain. Lack of oxygen to the brain is called cerebral hypoxia[1]. Brain cells are very sensitive to oxygen loss. Some begin to die less than 5 minutes after their oxygen supply stops.
- Heart. The heart takes up more oxygen for its weight than any other organ[2]. It cannot make enough energy without oxygen, so it depends on a steady supply[2]. As described above, heart muscle cells stop contracting within 1 to 2 minutes of hypoxia[2].
Some tissues can adjust to short dips in oxygen[1]. Even so, low oxygen that goes on for a long time can harm many organs. In organs scarred by fibrosis, low oxygen in the scarred areas helps keep the scarring going, as explained in What Is Fibrosis and How Does It Damage Organs?
Prompt treatment of hypoxia helps prevent permanent organ damage[1].
Frequently Asked Questions
How is hypoxia treated? Treatment depends on the cause[1]. Ongoing hypoxia can be treated with extra oxygen given through a mask or small tubes in the nose, and severe, sudden hypoxia may need a breathing machine in hospital[1]. Doctors also treat the cause, for example with a CPAP mask for sleep apnea, inhaled steroids for asthma or antibiotics for pneumonia[1].
How do doctors test for hypoxia? Doctors often start with a pulse oximeter, a sensor placed on a finger that measures oxygen in the blood[1]. An arterial blood gas test checks oxygen in blood taken from an artery. A six-minute walk test shows how far a person can walk in six minutes, and imaging such as X-rays or CT scans can help find the cause[1].
Who is most at risk of hypoxia? People with heart or lung diseases, such as COPD, emphysema or asthma, are at higher risk[1]. Infections such as pneumonia, flu and COVID-19 can also raise the risk, and anyone can have trouble breathing at high altitude[1].
Can hypoxia happen during sleep? Yes. Sleep apnea is one cause of hypoxia[1]. In sleep apnea, breathing repeatedly stops or becomes very shallow during sleep. It can be treated with a continuous positive airway pressure (CPAP) mask[1].
Can hypoxia be prevented? The best way to lower the risk is to manage any condition that can lower oxygen levels[1]. Other steps include not smoking, taking prescribed medicines as directed and planning ahead for travel to high altitudes[1].
What is the difference between hypoxia and anoxia? Hypoxia means that tissues receive less oxygen than they need. Anoxia means that they receive no oxygen at all. Anoxia is the most extreme form of oxygen shortage and damages tissue faster.
Morais C. What Happens When Tissues Do Not Receive Enough Oxygen? Hypoxia Explained [Internet]. BiologyWithin.com; 2026 Oct 21. Available from: https://www.biologywithin.com/2026/10/hypoxia-when-tissues-lack-oxygen.html
- Cleveland Clinic. Hypoxia. Cleveland Clinic Health Library.
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