10.2.1 CNS Trauma & Head Injury Flashcards
Mechanisms of Primary Injury in TBI
Impact (direct blow to head)
- Extradural, Subdural, Contusion, Intracerebral Hemorrhage, Skull Fracture
Inertial
- Concussion syndromes, Diffuse Axonal Injury
Ischemic / Hypoxic
Mechanisms of Secondary brain insults and what it results in
Systemic
- Arterial hypotension
- Hypoxia
- Hyper-/hypocapnia
- Hyper-/hypoglycemia
- Hyperthermia
- Disturbances of water and electrolyte balance
Intracranial
- Mass lesion
- Brain oedema, hyperemia
- ICP ⇑ , CPP ⇓
- Vasospasms
- Epileptic seizures
- Inflammation
Results in
1. ⬇️ Substrate transport within brain tissue
2. ⬇️ Cerebral blood flow
3. Altered Brain metabolism
=> causes tissue ischaemia
Cerebral ischaemia/insult classification
1. Global
- influence entire brain simultaneously
- result from cardiac arrest
- Hypoxia and ischemia of the brain
- Reduced cerebral blood flow can be due to raised intracranial pressure
2. Focal / local
- affects only area supplied by occluded artery
- Impaired cerebral blood flow or change in the extra-cellular environment due to altered/ damaged tissue
While passive damage is instantaneous, secondary brain insults occur from hours to several days after TBI and significantly alters the prognosis
What happens in secondary brain injury?
- necrosis
- apoptosis
- inflammation
- repair
- remodelling
Major pathway of secondary injury
progression of secondary injury after primary TBI
1. Microvascular stenosis
2. Astrocyte foot process swelling ➡️ breakdown of blood-brain barrier
3. Astrogliosis (proliferation of astrocytes)
4. Glutanate transport reversal
5. Ca2+ / Na+ influx
6. - Cellular depolarization
- Oxidative stress
- excitotoxicity
- mitochondrial dysfunction
- caspase cascade
7. Intra-axonal Ca2+ accumulation
8. Cytoskeletal breakdown ➡️ Axonal disconnection
9. Proinflammatory cytokine release ➡️ inflammation
⬇️ cerebral blood flow causes:
- ischaemic state
- low metabolic state
⬆️ cerebral blood flow
- hyperaemia / luxury perfusion
- causes vasodilatation
- uncontrolled swelling
Below what flow rate does it jeopardize the energy dependent sodium-potassium ATPase pumps and what does it cause?
18ml/100g/min
& it causes membrane failure
What is autoregulation?
Process whereby cerebral perfusion and cerebral blood flow are dissociated.
Normal CPP & CBF = 50ml/100g/min
What areas in the brain are most prone to TBI?
Watershed areas
Monro-Kellie Doctrine
- Establishes a relationship between intracerebral contents and pressure
- v.intracranial (constant) = v.brain + v.CSF + v.blood + v.mass lesion
- pressure is constant until compensatory mechanisms of reduced venous or atrial or CSF volume results in ⬆️ ICP once uncompensatory state is met
Uncompensatory state:
Venous - 75ml
Atrial - 75ml
Intracranial pressure
- After severe head injury, intracranial pressure is elevated in greater than 72%of patients2
- A complex relationship exists between CPP, CBF and ICP,
- ICP > 20mmHg is considered pathological, but must be considered in context
- Elevated ICP is a marker of poor outcome, but has not clearly been established as a causative factor
- After trauma, the parenchymal compartment may undergo an increase in volume due to:
• Oedema (vaso and cytogenic)
• Secondary to physical, ischemic or excitotoxic activity
• Traumatic mass lesions
• Obstruction of CSF flow
• Viscoelastic change (compliance of parenchyma)
Deranged calcium homeostasis and common final pathway as a result of Calcium overload
1. White Matter (Axons)
- Disconnection or secondary axotomy
- Progressive and delayed degenerative process
- Axonal membranes become leaky
2. Grey Matter (Neuronal Cells)
- Excitotoxic cell death
- Initiation of programmed cell death
- Post-synaptic receptor modifications
Common final pathway as a result of Calcium overload
- Early mitochondrial swelling
➡️Membrane depolarisation
➡️ Opening of membrane transition pores
➡️ Release of initiating factors of programmed cell death
- Mitochondrial dysfunction and energy failure
➡️Calcium influx due to ATP pump failing
Calcium influx initiates a destructive cascade
Slide 11
Post-traumatic glucose metabolism
- Initial 30 minutes post-injury glucose utilisation increases, followed by drop that remains persistently low for 5 - 10 days
- Early hyperglycolysis results from disrupted ionic gradients across neuronal cell membranes and activation of energy- dependent ionic pumps
- Evidence shows that there is impairment in oxidative metabolism following trauma, leading to a depletion of ATP with subsequent rise in anaerobic metabolism
➡️Rise in extracellular lactate is thought to be a result of decreased cerebral blood flow in the face of increased energy demand with upto 7x normal lactate concentration
➡️However there is evidence that high lactate levels exist even where blood flow limitations don’t exist - suggests that trauma affects mitochondrial phosphorylation, causing a shift toward anaerobic metabolism - Neuronal dysfunction is thus partly a result of acidosis, but also effected by concurrent membrane damage, ionic flux, disruption of the blood brain barrier and cerebral oedema
