Hypoxia: inadequate oxygenation of tissues (cf shock)

Oxygen required for

• Oxidative phosphorylation (mitochondrial electron transport system)
• Last reaction is oxgen to receive electron
• Forms ATP for energy

Oxygen Content

Haemoglobin x Oxygen % saturation + Partial pressure of arterial oxygen (amount dissolved in plasma)

4 Haem groups (Fe 2+): carries 8 atoms of oxygen
Oxygen saturation = amount attached to haem molecule

Oxygen flow: alveoli, interface, dissolves in plasma, diffuses through RBC membrane, attaches to Hb groups.

Partial pressure of oxygen

Ischaemia: Decrease in arterial blood flow

Causes of ischaemia:
Thrombosis - blocks arterial blood flow
Decrease in cardiac output (hypovolaemia, shock)
Hypoxaemia: a process that leads to hypoxia (cf acidaemia and acidosis)

Dalton's Law: partial pressure of gases must equal 760mmHg.

If PO2 goes up, PCO2 must go down and vice versa

Causes of tissue hypoxia: 

1. Ventilation defects: produce shunt

• Interpulmonary shunting - eg ARDS

2. Perfusion defects: produce increased dead space

• Pulmonary embolus 

3. Diffusion defect

• Sarcoidosis causing fibrosis
• Pulmonary oedema / heart failure (J-reflex innervated by 10th nerve - causes dyspnoea; unable to take full breath)

4. Haemoglobin disorders

• Anaemia
• Carbon monoxide poisoning - 240 times more affinity for displacement (treated with 100% oxygen); commonest symptom is headache
• Methaemoglobinaemia (Fe 3+ on haem group - oxygen unable to bind to it): red cells have a methaemoglobin reductase system to prevent this occuring - prevalent in oxidising agents (nitrates, sulphur drugs like dhapsone).  Treatment is vitamin C (reducing agent), methylene blue.

Haemoglobin right shift (Bohr effect): DPG, acidosis, temperature, high altitude - meaning Hb has less affinity for O2 therefore releases oxygen to tissues. 

5. Oxidative pathway problems

• Cytochrome oxidase pathway (Carbon monoxide blocks this pathway, cyanide)
• Mitochondrial uncoupling of mitochondrial membranes - uncoupling agents dinitrophenol, alcohol, salicylates - causes

Consequence of Tissue Hypoxia

• Decreased ATP
• Anaerobic glycolysis - produces lactic acid (from pyruvate, due to an increase in NADH) - produces 2ATP per glucose
• Leads to increased anion gap
• Increased acid in cell denatures the inherent proteins and enzymes (causes coagulation necrosis - cell is unable to autodigest itself from the denatured enzymes)
• Failure of all ATP-ase pumps - leads to cellular swelling (failure to remove Na); Ca-ATPase leads to calcium entering cells and activates enzymes

Free radicals

• Compound containing unpaired electron in outer orbit
• Highly reactive and destructive capacity
• Oxygen free radicals (super-oxide free radicals, retrolentinal, bronchopulmonary fibrodysplasia)
• Hydroxyl free radicals ('OH): causes cancer associated with radiotherapy
• Iron overload free radicals