Pathogenesis of Perinatal Brain Injury Flashcards
What does perinatal brain injury mean?
Injury to the brain pre, during and post time of birth
What is the incidence of peri-natal brain injury in term babies?
3-4 per 1000 term births result in death or neurological impairment
Whats the incidence of peri-natal brain injuries in preterm babies?
8-13% of all births are preterm
>50% will be brain damaged i.e cerebral palsy, neurological impairment and handicap
What are the types of brain injury in the perterm baby?
Focal cystic necrosis
Non-cystic oligiodendrocyte cell death and diffuse myelonation failure
What is focal cystic necrosis?
Death of all cellular elements resulting in big holes in the brain (severe)
What matter does the brain consist of?
grey = cell bodies and synapses
white matter = axons, myelon, astrocytes
What is Non-cystic oligiodendrocyte cell death and diffuse myelonation failure?
Oligiodendrocytes myelonate axons, therefore the damage occurs in the white matter.
Grey matter and cerebral cortex spared from damage
What does MRI of white matter injury show?
- Decreased white matter volume
- Lesions / cavities in the white matter
- Ventricularomeagly (increased size)
Diffuse occurance
How does white matter damage present on MRI?
Appears more white
How does the size of preterm babies compare to term babies?
Vastly smaller
What sort of brain injuries are term babies susceptible to?
White matter injuries and grey matter injuries as their neurons are more developed
What sort of WMI are term babies suceptible to?
Cystic and diffuse white matter injuries (same as preterm babies)
What sort of GMI are term babies suceptible to?
(preterm dont get this) Widespread grey matter injury - Selective neuronal death (small insult particularly in hippocampus, cortex and striatum) - Laminar cell death (regions) - Focal grey matter lesions
What is one of the main outcomes of WMI?
Cerebral Palsy
How common is CP?
Child 10x more likely to get CP than cancer
One born every 20 mins in USA with CP
What problems are associated with CP?
Arm and leg weakness Abnormal walking if at all Curvature of the spine Swallowing / feeding problems Learning disabilites
Why is when babies get brain injured (perinatal) important?
Determines the cause of brain injury
Potential interventions / treatment stratagies
What are some causes of perinatal brain injury?
Prolonged labor
Cord knots
Occluded cord
BP instability
What is the actual reason for perinatal brain injury?
Hypoxia-ischemia Infection - Maternal/fetal, post natal - cytokine production Accident/trauma Teratogens
What are teratogens?
- Drug use, alcohol, smoking, CO
- Can cause direct effects on the brain and secondary actions on CV system - leading to poor blood flow, oxygenation, nutrient supply (perfusion)
What are some causes of fetal hypoxia ischemia?
Placental abruption Occluded umbilical cord CV instability (BP) Congential heart defects Cardiorespiratory arrest Preterm lung development
What is placental abruption?
- Placental lining is separated from the uterus
- Supply of O2 and nutrients to the fetus is deminished
What is hypoxia, hypoxemia?
Low O2 (PO2) Low blood O2
What does hypoxia result in?
Hypercapnia = respiratory acidosis
Metabolic acidosis - accumulation of lactic acid in the blood due to anaerobic respiration
Describe the fetal hypoxia-ishemica flow diagram
Oxygen / Nutrients are supplied by the mother via placenta and umbilical cord
- Impaired O2 delivery i.e umbilical cord occlusion
Results In:
1) Fetal hypoxia -> Anaerobic metabolism and lactate production -> metabolic acidosis
2) Impaired waste removal -> Accumulation of CO2 -> Respiratory acidosis
Hypoxia and acidosis result in:
- Impaired CV system that leads to reduced brain blood flow (perfusion) , O2 delivery
= Hypoxic ischemia
= Brain injury
What is cellular homeostasis?
Ability of a cell to maintain its normal function over a range of different conditions
- loss of cellular function causes cell damage
What are they key homeostatic mechanisms?
1) ICF/ECF ion gradient
2) Aerobic and anaerobic production of ATP
3) Delivery of O2, nutrients to brain cells
4) Matching of cellular metabolic activity to energy supply
What are some characteristics of a normal cell?
- Membrane potential
- Uses 33% all ATP on Na/K ATPase pump
- Energy failure results in loss of membrane potential and cell damage
- Mitochondria produce ATP
- Brain doesnt store ATP
- Requires glucose in blood
- Cell depolarisation (loss of NaKATPase) can lead to edema
How does BP and brain injury correlate?
If BP is low then brain perfusion is poor, thus low O2 and glucose, Brain cell death increases
What are the fetal responses to maintain brain perfusion during asphyxia?
- Decreased HR
- Peripheral vasoconstriction and redistribution of flow to the important organs, increasing BP and O2/glucose delivery to the brain
What happens to brain perfusion with prolonged asphyxia?
- BP is not sustained despite defenses.
- Blood flow and perfusion is decreased therefore brain damage occurs
How does the brain match its metabolic activity to its energy supply?
- During reduced energy supply, brain tries to reduce activity
- Protective response to prolong time before injury
- In part adenosine mediated as its an inhibitory neurotransmitter (lowers CNS activity)
What are the three types of brain cell death?
necrosis and apoptosis
Also lysis
What is the difference between apoptosis and necrosis?
Necrosis is cell death due to the insult, results in inflammation etc
Apoptosis is programmed cell death and does not result inflammation, cells that are bystanders and not directly influenced by the insult can undergo apoptosis as the brain remodels itself
Why do some brain cells lyse?
cell lysis is caused by oedema = excissive osmosis probably due to cell depolarisation.
How does apoptosis occur?
- Tightly regulated physiological process
- Selective cell death
- No inflammation
- Energy dependent signalling pathway
- Upregulated with injury
What sort of process is brain injury?
It is an evolving one
What are the phases of brain injury evolution?
: Insult - Recovery - Re-organisation
: Primary- Reperfusion + Latent phase and secondary phase - tertiary phase
When does most brain injury occur?
Not in the primary insult phase. Normally during recovery when the brain reperfuses
Primary Phase = necrosis
Recovery and reorganisation = apoptosis
