In one breath
Hypoxia means the tissues are short of O₂, either because too little reaches them or because they cannot use what arrives. It comes in four types, named after the link in the O₂ chain that fails: the arterial PO₂ (hypoxic), the Hb that carries O₂ (anemic), the blood flow (stagnant) or the cell’s own use of O₂ (histotoxic). Only hypoxic hypoxia lowers PaO₂, and only histotoxic hypoxia leaves the venous PO₂ high. The brain suffers first: mild hypoxia mimics drunkenness, and a sudden severe fall knocks a person out in about 15 seconds.
Builds on: Oxygen transport · Oxygen–hemoglobin dissociation curve · Ventilation–perfusion ratio · Leads to: Oxygen therapy · Asphyxia, hypercapnia and hypocapnia
What hypoxia is
Hypoxia is a deficiency of O₂ at the tissue level. It arises in one of two ways:
- the supply of O₂ to the tissue falls, or
- the tissue cannot use the O₂ that reaches it.
Four types
| Type | What fails | PaO₂ |
|---|---|---|
| Hypoxic | O₂ getting into arterial blood | Low |
| Anemic | Hb available to carry O₂ | Normal |
| Stagnant | Blood flow to the tissue | Normal |
| Histotoxic | The cell’s use of O₂ | Normal |
- Worth knowing, though not in your pages: cyanosis needs plenty of reduced Hb in the capillaries. So it is seen in hypoxic and stagnant hypoxia, but not in CO poisoning (COHb is cherry red), and seldom in severe anemia or histotoxic hypoxia.
Hypoxic hypoxia
Definition: hypoxia caused by a low PO₂ in arterial blood.
Mechanism: with less O₂ pressure in the arterial blood, less O₂ reaches the tissues. The fault lies either in the air breathed, which holds too little O₂, or in a disease of the respiratory apparatus that stops enough O₂ getting in.
Causes:
- Low inspired PO₂: high altitude, closed chambers.
- Hypoventilation: airway obstruction, paralysed respiratory muscles, a depressed respiratory centre, scoliosis.
- Diffusion defect: pulmonary edema, pulmonary fibrosis, lung collapse.
- Ventilation–perfusion mismatch, where blood perfuses poorly ventilated alveoli: large A-V shunts, atelectasis, lung collapse, cyanotic congenital heart disease.
Causes 2–4 lie in the breathing apparatus itself, so together they are called respiratory hypoxia.
| Rapid ascent to | What happens |
|---|---|
| 3000 m (10,000 ft) | Alveolar PO₂ falls to about 60 mmHg: hypoxia begins |
| Above 5000 m (15,000 ft) | Severe hypoxic symptoms |
How the body copes with altitude is on Acclimatization to high altitude and High altitude illness. Shunts and mismatch are explained on Ventilation–perfusion ratio.
Anemic hypoxia
Definition: PaO₂ is normal, but there is not enough usable Hb to carry the O₂.
Conditions:
- anemia (a low Hb concentration)
- carbon monoxide poisoning
- altered Hb, such as methemoglobin
Mechanism:
- The inspired PO₂ and the lung’s diffusing capacity are both normal, so PaO₂ is normal. Delivery falls only because too little Hb is free to carry the O₂.
- In mild to moderate anemia, tissue supply usually holds up, because red-cell 2,3-DPG rises at the same time and helps Hb unload O₂ (see Oxygen–hemoglobin dissociation curve).
- These patients still become severely hypoxic on exercise, when their limited delivery cannot keep up.
Carbon monoxide poisoning
- CO binds Hb about 210 times more avidly than O₂ does, forming carboxyhemoglobin (COHb), also called carbomonoxyhemoglobin.
- CO leaves COHb very slowly, so those binding sites stay closed to O₂.
- The Hb concentration is normal, yet the Hb cannot deliver O₂. That is why CO poisoning counts as anemic hypoxia.
- For whatever oxyhemoglobin is left, the dissociation curve shifts left, so even that O₂ is given up less readily.
CO poisoning is not hypoxic hypoxia
The air breathed and the lungs are normal, so PaO₂ stays normal. What fails is Hb that is present but taken up by CO. The cherry-red colour of COHb, and why the usual warning signs go missing, are on Oxygen–hemoglobin dissociation curve.
Stagnant hypoxia
Other names: hypoperfusion hypoxia, sometimes ischemic hypoxia, and circulatory hypoxia.
Definition: hypoxia caused by reduced blood flow to the tissues, so that the blood stagnates in them.
Mechanism:
- The arterial blood has a normal O₂ content. The tissue goes short because that blood moves through it too slowly.
- Flow falls either because cardiac output falls or because some other cause cuts the flow.
- If the stagnation is chronic or complete, lactate builds up. The local acidosis it causes inhibits cell metabolism.
Seen in:
- heart failure
- shock
- vascular obstruction, which makes a single organ hypoxic
Histotoxic hypoxia
Definition: the O₂ supply is normal, but the tissue cannot use the O₂.
- Because the O₂ is not taken up, the venous PO₂ stays high. This is the signature of the type.
- It usually follows poisoning of the tissue by cyanide or a similar poison.
Mechanism, by cause:
| Cause | What it blocks |
|---|---|
| Cyanide | Cytochrome oxidase, so tissue oxidation stops |
| Severe diphtheria | Synthesis of one of the cytochromes |
Treating cyanide poisoning, as your book gives it:
- Methylene blue or nitrites produce methemoglobin.
- Methemoglobin takes up cyanide to form cyanmethemoglobin, which is not toxic.
- Hyperbaric O₂ also helps.
Methylene blue: out of date
Your book pairs methylene blue with the nitrites. Nitrites, which it also names, are the safe example of a MetHb former in an exam answer. Worth knowing, though not in your pages: methylene blue is today the treatment for methemoglobinemia, since it turns MetHb back into Hb, and it is not a standard cyanide antidote. Nitrites are given with sodium thiosulfate, which turns cyanide into the far less toxic thiocyanate, and hydroxocobalamin, which binds cyanide directly, is now widely used.
Effects of hypoxia
- Hypoxia hits the CNS hardest, above all the higher centres.
- How it shows depends on its severity, duration and type.
Acute and subacute hypoxia
- It looks like acute alcoholism. The leading signs are impaired judgment and motor incoordination.
- If it lasts longer: fatigue, drowsiness, nausea, headache, hyperventilation and dyspnea, apathy, poor attention, slow reactions, less capacity for work, confusion and disorientation.
- Severe hypoxia raises the blood pressure (hypertension).
- Long and severe hypoxia depresses the brainstem, and the patient dies of respiratory failure.
Acid–base changes:
| What happens | Result |
|---|---|
| More anaerobic glycolysis, so more lactic acid | Metabolic acidosis |
| Chemoreceptors drive hyperventilation | Respiratory alkalosis |
| The two together | Serum HCO₃⁻ falls |
Effects on cells: HIFs
- Hypoxia produces hypoxia-inducible factors (HIFs), transcription factors built of α and β subunits.
- When tissue O₂ is adequate, the α subunits are cleared from the cell quickly.
- In hypoxia, α and β dimerize. The α–β dimer switches on the genes for erythropoietin and angiogenic factors.
- This is one reason hypoxic tissue grows new vessels (angiogenesis, or neovascularization).
Effects on the brain
Brain tissue is extremely sensitive to hypoxia. When the inspired PO₂ falls suddenly below 20 mmHg:
| Outcome | Time |
|---|---|
| Consciousness lost | About 15 s |
| Death, if it continues | 4–5 min |
- The typical setting is a sudden loss of cabin pressure in an aircraft flying above 16,000 m.
- Milder hypoxia gives drunk-like symptoms: disorientation, impaired judgment, headache, drowsiness.
Chronic hypoxia
- Polycythemia, because erythropoietin output rises.
- Local hypoxic vasodilation, which increases blood flow to the tissue.
Applied: hypoxia that does good
Because hypoxia drives erythropoietin, your book points out that mild physiological hypoxia, such as a stay at high altitude, can sometimes be good for health (see Acclimatization to high altitude).
Draw it: where each type breaks the O₂ chain
Draw four boxes left to right, joined by arrows: “inspired air and alveoli”, “Hb in arterial blood”, “blood flow to tissue”, “mitochondria (cytochrome oxidase)”. Under each box write the type that fails there: hypoxic, anemic, stagnant, histotoxic. Below that add the PaO₂ (low, normal, normal, normal) and one example each (altitude, CO, shock, cyanide).
Exam-answer skeleton: "Define hypoxia; classify it and describe each type" (long essay)
- Definition: O₂ deficiency at the tissue level, from poor supply or failed use.
- The four types and the link each breaks, in a table with PaO₂.
- Hypoxic: low PaO₂; the four causes with examples; the altitude figures; causes 2–4 as respiratory hypoxia.
- Anemic: normal PaO₂ but too little usable Hb; anemia, 2,3-DPG and exercise; CO poisoning (210 times, COHb, left shift).
- Stagnant: normal arterial O₂ content but slow flow; heart failure, shock, vascular obstruction; lactate acidosis.
- Histotoxic: normal supply, high venous PO₂; cyanide on cytochrome oxidase, diphtheria; treatment.
- Effects: CNS first and drunk-like; acid–base changes; HIFs; the brain’s 15 s and 4–5 min; chronic polycythemia and vasodilation.
- A note on O₂ therapy in each type and on 100% O₂ toxicity (see Oxygen therapy).
Asked in exams
- Hypoxia and its types: Jul 2010, 4 marks · Jul 2011, 10 marks · Nov 2013, 2 marks · Nov 2017, 2 marks · Apr 2021, 3 marks · Apr 2021, 4 marks
- Hypoxic hypoxia: Jan 2023, MCQ
- Anemic hypoxia, including CO poisoning: Dec 2015, 4 marks · Jan/Feb 2022, MCQ
- Stagnant hypoxia: Sep/Oct 2019, 2 marks · Apr 2023, MCQ