1.3 about 28 minDeep Learning viewL1 p.9–17

Hypoxia, ischemia and oxygen delivery

Oxygen travels from inspired air to the alveolus, into arterial blood, onto hemoglobin, through tissue blood flow and into the mitochondrion. Each disorder in this section breaks the chain at a different link.

Hypoxia, anoxia, hypoxemia, ischemia

L1 p.9

  • Hypoxia

    Meaning
    Too little oxygen at the tissue level, from any cause
    Example
    Anemia, CO poisoning, lung disease, ischemia

  • Anoxia

    Meaning
    Complete absence of oxygen
    Example
    Cardiac arrest; strangulation

  • Hypoxemia

    Meaning
    Low arterial oxygen tension (PaO₂) on a blood gas; clinically significant below about 60 mm Hg, with SaO₂ below about 90%
    Example
    Pneumonia, high altitude, hypoventilation

  • Ischemia

    Meaning
    Reduced arterial inflow (or impaired venous outflow) to a tissue
    Example
    Coronary thrombosis, cerebral embolism

Find where oxygen fails

L1 p.9–15

Follow one oxygen molecule. Its inspired pressure (PIO₂) depends on the oxygen fraction of air and on barometric pressure. In the alveolus, water vapour and carbon dioxide dilute it to the alveolar pressure (PAO₂). It diffuses into capillary blood, where it sets the arterial pressure (PaO₂), the driving pressure, not the amount carried.

Most oxygen rides on hemoglobin. SaO₂ is the percentage of hemoglobin's binding sites that carry oxygen; it depends on PaO₂ and on hemoglobin working normally. The arterial oxygen content is roughly 1.34 × Hb × SaO₂ plus a small dissolved fraction (0.003 × PaO₂): halve the hemoglobin and you halve the content even with a perfect PaO₂ and SaO₂. Delivery to a tissue is content multiplied by blood flow. Finally the tissue must unload the oxygen and the mitochondria must use it at cytochrome oxidase.

Interactive model

0 of 7 located

High altitude. A trekker at 5,000 m with a normal heart and lungs. Tap the link where oxygen's journey fails.

Five of the seven scenarios have a normal PaO₂: tissue hypoxia does not require hypoxemia.

Oxygen's journey has six links. Hypoxemia breaks one of the first two; anemia, CO and methemoglobinemia break the hemoglobin links; ischemia breaks flow; cyanide breaks use.L1 p.9–15

Five causes of hypoxemia

L1 p.10

  • Low inspired oxygen

    Mechanism
    PIO₂ falls, so PAO₂ and PaO₂ fall with it
    Examples
    High altitude; breathing a low-oxygen mixture
    Alveolar–arterial (A–a) gradient
    Normal

  • Hypoventilation

    Mechanism
    Too little fresh air reaches alveoli; rising alveolar CO₂ displaces O₂
    Examples
    Opioid or sedative overdose, brainstem depression, neuromuscular weakness
    Alveolar–arterial (A–a) gradient
    Normal (PaCO₂ high)

  • Ventilation–perfusion (V/Q) mismatch

    Mechanism
    Some units get blood but too little air (low V/Q); others air without blood (high V/Q)
    Examples
    COPD, asthma, pneumonia, pulmonary embolism
    Alveolar–arterial (A–a) gradient
    Increased

  • Diffusion impairment

    Mechanism
    Thickened alveolar–capillary barrier slows oxygen transfer
    Examples
    Interstitial fibrosis (worse with exercise)
    Alveolar–arterial (A–a) gradient
    Increased

  • Right-to-left shunt

    Mechanism
    Blood reaches the arterial side without meeting ventilated alveoli
    Examples
    Cyanotic congenital heart disease (tetralogy of Fallot); intrapulmonary: atelectasis, consolidation, diffuse alveolar damage (RDS/ARDS)
    Alveolar–arterial (A–a) gradient
    Increased

Three ways ventilation and perfusion can fail to match

Poorly ventilated alveoli (low V/Q)

  • Partly blocked airways: asthma, COPD, mucus
  • Blood leaves these units under-oxygenated
  • Some air still arrives, so extra oxygen raises their PAO₂

Poorly perfused alveoli (high V/Q)

  • Pulmonary embolism blocks flow to ventilated alveoli
  • Their ventilation is wasted (dead space), which by itself does not lower PaO₂
  • Hypoxemia arises because blood is diverted to the rest of the lung, creating low-V/Q areas, and from some shunting

Blood bypassing ventilation (shunt, V/Q = 0)

  • Atelectasis or consolidation: perfused but airless alveoli
  • Intracardiac right-to-left shunt
  • Shunted blood never meets the inspired oxygen

Who responds to supplemental oxygen

L1 p.10

Giving oxygen raises the oxygen pressure only in alveoli that receive air. Whether that helps depends on where the chain is broken. These are mechanism comparisons, not treatment rules: the size of the response varies with severity and with how much of the lung is affected.

  • Low inspired oxygen

    Response of PaO₂ to more inspired oxygen
    Corrects
    Why
    The problem was the oxygen in the air

  • Hypoventilation

    Response of PaO₂ to more inspired oxygen
    Improves PaO₂, but CO₂ retention persists
    Why
    Ventilation, not oxygen, must be restored to clear CO₂

  • Low V/Q and diffusion impairment

    Response of PaO₂ to more inspired oxygen
    Improves well
    Why
    Some air reaches the affected units, and the higher pressure drives more oxygen across

  • Large shunt

    Response of PaO₂ to more inspired oxygen
    Improves little
    Why
    Shunted blood never meets alveolar gas; normal units are already nearly saturated and cannot compensate. The slide's example: diffuse bilateral disease such as RDS

  • Anemia, CO, methemoglobinemia, cyanide

    Response of PaO₂ to more inspired oxygen
    PaO₂ rises, content barely changes
    Why
    The defect is in hemoglobin or in use, and dissolved oxygen adds little. In CO poisoning high-flow or hyperbaric oxygen is still given, because it shortens carboxyhemoglobin's half-life

Adapting to high altitude

L1 p.11

Air at altitude still contains about 21% oxygen, but barometric pressure is lower, so inspired, alveolar and arterial PO₂ all fall with a normal A–a gradient. The body adapts in stages, as the lecture's diagram shows:

  • Ventilation ↑ (hypoxic drive)

    Effect
    Raises PAO₂; lowers PaCO₂ (respiratory alkalosis, later compensated by the kidney)
    Timing
    Minutes to days

  • Erythropoietin ↑ from the kidney

    Effect
    More red cells: hemoglobin and hematocrit rise, so content rises
    Timing
    Days to weeks

  • 2,3-BPG ↑ in red cells

    Effect
    Shifts the dissociation curve right (higher P50), easing unloading in tissues
    Timing
    Hours to days

  • Hypoxic pulmonary vasoconstriction

    Effect
    Pulmonary artery pressure rises; chronically, right ventricular hypertrophy
    Timing
    Persists while hypoxic

When the blood carries or releases too little

L1 p.12–14

Where the process failsL1 p.12–15

  • Hypoxemia (lung disease)

    PaO₂
    ↓
    Hemoglobin amount or function
    Normal
    Tissue oxygen use
    Normal when oxygen arrives
    Key clue
    Low PaO₂ and SaO₂

  • Anemia

    PaO₂
    Normal
    Hemoglobin amount or function
    Amount ↓; SaO₂ normal; content ↓
    Tissue oxygen use
    Normal
    Key clue
    Pallor, fatigue; low hemoglobin

  • Methemoglobinemia

    PaO₂
    Normal
    Hemoglobin amount or function
    Function ↓: Fe³⁺ cannot bind O₂; remaining hemes hold O₂ more tightly (impaired unloading); true SaO₂ ↓
    Tissue oxygen use
    Normal
    Key clue
    Cyanosis unresponsive to oxygen; chocolate-brown blood; pulse oximeter reads about 85%

  • Carbon monoxide

    PaO₂
    Normal
    Hemoglobin amount or function
    Function ↓: carboxyhemoglobin; curve shifts left; true SaO₂ ↓
    Tissue oxygen use
    Also ↓: CO binds cytochrome oxidase
    Key clue
    Headache first; pulse oximeter falsely normal

  • Cyanide

    PaO₂
    Normal
    Hemoglobin amount or function
    Normal; SaO₂ normal
    Tissue oxygen use
    Use ↓↓: cytochrome oxidase blocked
    Key clue
    Severe lactic acidosis; oxygen-rich venous blood

  • Ischemia

    PaO₂
    Normal
    Hemoglobin amount or function
    Normal
    Tissue oxygen use
    Falls because nothing arrives
    Key clue
    Territory of an occluded vessel

True SaO₂ means saturation measured by co-oximetry. Standard pulse oximeters cannot distinguish carboxyhemoglobin from oxyhemoglobin and misread methemoglobin.

Methemoglobinemia in more detailMore detail

Hemoglobin's iron must be ferrous (Fe²⁺) to bind oxygen. Oxidant stress converts it to ferric (Fe³⁺), forming methemoglobin, which cannot carry oxygen. The remaining normal hemes in the same molecule hold their oxygen more tightly, so unloading in tissues is also impaired. Common causes are dapsone, local anaesthetics such as benzocaine, and nitrites from food or contaminated well water. PaO₂ is normal; true SaO₂ falls.

The lecture links symptoms to rising levels: cyanosis appears first, then headache, anxiety, dyspnea and tachycardia, and at high levels confusion, lethargy and lactic acidosis as tissues turn to anaerobic glycolysis.

Carbon monoxide in more detailMore detail

CO comes from incomplete combustion: car exhaust, smoke inhalation, wood stoves, generators run indoors and blocked heater vents, typically in the cold months. Hemoglobin binds CO far more avidly than oxygen, forming carboxyhemoglobin, which lowers oxygen content and shifts the curve left so less oxygen is released. CO also binds cytochrome oxidase and myoglobin. PaO₂ stays normal and a pulse oximeter reads falsely normal.

Headache is the first symptom, then dizziness, dyspnea, seizures and coma. The brain is the target: the globus pallidus and cerebral white matter are injured by hypoxia combined with CO-triggered inflammation and lipid peroxidation, and globus pallidus lesions can become necrotic and cavitate over days to weeks. Delayed neurologic deficits (memory problems, apathy) appear in a substantial minority of survivors. Rhabdomyolysis can occur.

Teaching schematic

deep white matterglobus pallidusSchematic coronal section · not to scale
Carbon monoxide injury targets the globus pallidus and cerebral white matter. Schematic coronal section.L1 p.13–14

Cyanide: delivered but not used

L1 p.15

Cyanide poisoning most often comes from smoke in house fires, as burning plastics, foams, wool and silk release hydrogen cyanide. Other sources are prolonged nitroprusside infusion, amygdalin in apricot, peach and plum kernels and bitter almonds, industrial exposure and deliberate ingestion.

Cyanide binds the ferric iron of cytochrome c oxidase (complex IV) and halts electron transport. Oxygen arrives normally (PaO₂ and SaO₂ are normal) but cannot be used, so tissues extract less of it and venous blood stays oxygen-rich. ATP falls, glycolysis surges and a severe lactic acidosis develops. The organs with the highest oxygen use fail first: the brain (confusion, seizures, coma) and the heart (arrhythmias, cardiovascular collapse).

Tissues that suffer first

L1 p.16

When oxygen delivery falls throughout the body (shock, cardiac arrest, severe hypotension), injury is not evenly spread. Cells with the highest demand and the most precarious supply die first. These patterns appear repeatedly in cases.

  • Neurons: hippocampal CA1 (Sommer sector), cerebellar Purkinje cells, cortical layers 3, 5 and 6

    Why it is vulnerable
    Very high energy demand; almost no glycogen reserve
    What you see
    Red, shrunken neurons; laminar necrosis of the cortex

  • Watershed zones

    Why it is vulnerable
    Border zones between two arterial territories (for example ACA and MCA in the brain; the splenic flexure of the colon) receive the least pressure when flow falls
    What you see
    Strips of infarction at territory borders after hypotension

  • Subendocardial myocardium

    Why it is vulnerable
    Farthest from epicardial coronary arteries and compressed during systole
    What you see
    Subendocardial infarction after hypotension or severe coronary narrowing

  • Centrilobular hepatocytes (zone 3)

    Why it is vulnerable
    Last to receive blood after periportal hepatocytes have extracted oxygen
    What you see
    Centrilobular necrosis in shock or heart failure

  • Kidney: proximal tubule straight segment (S3) and medullary thick ascending limb

    Why it is vulnerable
    High transport work in a region where oxygen tension is low
    What you see
    Acute tubular injury (necrosis) after hypoperfusion

The slide lists “renal cortex and medulla”; the table names the specific segments that are most vulnerable.

Knowledge check · 1.3

Answer, read why, and try again whenever you like. Answers are kept in both study modes.

0 of 5 correct
  1. Q1Oxygen content in anemiaL1 p.12

    A woman with heavy menstrual bleeding has hemoglobin 7 g/dL, PaO₂ 95 mm Hg and SaO₂ 98%.

    What is reduced?

  2. Q2Carbon monoxideL1 p.12–13

    A family runs a gasoline generator in their garage during a winter storm. Several members develop headaches and dizziness. Pulse oximetry reads 99% in each.

    Which statement is correct?

  3. Q3MethemoglobinemiaL1 p.12

    After benzocaine spray before endoscopy, a patient becomes cyanotic. Arterial blood is chocolate-brown, PaO₂ is normal, and pulse oximetry stays near 85% despite supplemental oxygen.

    What is the mechanism?

  4. Q4Shunt and supplemental oxygenL1 p.10

    After abdominal surgery, a patient's entire left lower lobe collapses. He remains hypoxemic on high-flow oxygen.

    Why does oxygen help so little?

  5. Q5Tissues vulnerable to hypoxiaL1 p.16

    After an episode of profound hypotension, which region of the liver is most likely necrotic?

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