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PH-FD01

Cell injury and hypoxia

How oxygen reaches the mitochondria to make ATP, what fails when it does not arrive, and why early hypoxic injury can recover while prolonged injury breaks membranes and kills the cell.

By the end, you can

  • Trace oxygen from the blood to the mitochondria and explain how oxidative phosphorylation makes ATP.
  • Distinguish hypoxia from ischaemia and name the four main ways oxygen delivery or use fails.
  • Explain how falling ATP causes cell swelling, anaerobic glycolysis and acidosis inside the cell.
  • Distinguish reversible from irreversible injury and relate membrane damage to enzymes found in the blood.
  • Explain why reperfusion can add injury and why some tissues are injured sooner than others.
  • Recognise the classic appearances of reversible and irreversible injury, and explain how oxygen, reperfusion, antidotes and lowering demand act on the mechanism.

What it is

Cell injury is damage that disturbs a cell’s structure or function. Its commonest cause is hypoxia, too little oxygen for the cell’s needs. Ischaemia, too little blood flow, causes hypoxia and also stops the delivery of glucose and the removal of waste, so it injures faster. Injury is reversible while the cell can recover once oxygen returns, and irreversible once its mitochondria and membranes are badly damaged.

4 types to tell apart
Hypoxaemic hypoxia
Too little oxygen enters the arterial blood, as in lung disease or at altitude. Arterial oxygen tension and saturation are low.
Anaemic hypoxia
Too little working haemoglobin carries oxygen, as in anaemia or carbon monoxide poisoning. Arterial oxygen tension can be normal.
Ischaemic (circulatory) hypoxia
Blood flow fails, locally (a blocked artery) or everywhere (shock). Waste also builds up, so injury is faster.
Histotoxic hypoxia
Oxygen arrives but the cell cannot use it, because a poison such as cyanide blocks the electron transport chain.

US spelling: ischaemia → ischemia, haemoglobin → hemoglobin, litre → liter.

Normal function

Oxygen, mitochondria and ATP

Oxygen crosses from the alveoli into the blood, where almost all of it binds haemoglobin in red cells. The heart pumps it to the capillaries, where it diffuses through the tissue fluid and the to the . Oxygen delivery depends on two things: how much oxygen each litre of blood carries, and how much blood flows.

In the mitochondrion, the electron transport chain on the passes electrons from food fuels to oxygen, the final acceptor. The energy released pumps protons across the membrane, and ATP synthase uses that gradient to make ATP. With oxygen, one glucose yields about 30 ATP; glycolysis in the cytosol alone yields only 2.

A cell spends its ATP continuously. The sodium–potassium pump keeps sodium out and so controls cell volume; calcium pumps keep cytosolic calcium about ten-thousand-fold lower than outside; and ribosomes use ATP to make proteins. Reserves last only seconds to minutes, so ATP supply must match demand.

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