Perinatal Asphyxia and Infection Flashcards
Hypoxia-Ischaemia at birth
Infants need resuscitations at birth
–> may have absent HR< infant not breathing
–> may require airway, respiratory and haemodynamic support
Infant subsequently encephalopathic
Hypoxia-ischaemia warnings
Decreased foetal warnings
Sentinel events- placental abruption, uterine rupture, cord prolapse
HI Preserved blood supply
CNS
Myocardium
Adrenals
HI Vulnerable blood supply
Kidneys
GI tract
Liver
Muscle
Encephalopathy in newborn
Abnormal neurologic function + consciousness level
Abnormalities of tone and reflexes
Autonomic dysfunction
Seizures
Sarnat study of perinatal asphyxia
Stage 1- less than 24 hrs, hyperalertness, uninhibited Moro and stretch reflexes, symp. effects and normal EEG
Stage 2- obtundation, hypotonia, multifocal seizures, EEG periodic pattern sometimes preceded by continuous delta activity
Stage 3- stuporous, flaccid and brain stem + autonomic functions suppressed
Foetal/perinatal hypoxia +/or ischaemic cerebral insult
Leads to primary neuronal injury Primary energy failure Derangement of cellular function Secondary energy failure Secondary neuronal injury, further necrosis and apoptosis
Energy consequences Hypoxia-Ischaemia
Phosphorus spectra normal first few hours after resuscitation
12-24 hours- progressive decline in PCr/Pi ratio
Delayed ATP decline
Secondary energy failure
Acute hypoxia ischaemia –> reperfusion (after resuscitation) –> secondary energy failure (several hours after reperfusion)
Cerebral Hypoxic-Ischaemic injury
Primary neuronal death
Resuscitation – Reperfusion, Oxygenation
Cerebrovascular dysfunction Glutamate release Free radicals Calcium entry Apoptosis
Secondary neuronal death
Mechanisms of brain injury in Hypoxia-Ischaemia
Glucose + O2 deprivation Energy depletion – decreased ATP Glutamate receptor activation Accumulation of intracellular Ca Free radicals – NO, superoxide, Fe, H2O2, Lipid peroxidation Oligodendroglial death Apoptosis
Neuroprotection targets
Decreased energy depletion
Glutamate
Inhibition of leukocyte/microglial/cytokine effects
Blockade of downstream intracellular events
Decreased energy depletion
Glucose
Hypothermia
Barbiturates
Glutamate
Inhibit glutamate release (Ca channel blockers, magnesium, adenosine, hypothermia)
Fix glutamate uptake impairment - hypothermia
Glutamate receptor blockade- magnesium
Blockade of downstream intracellular events
Hypothermia Free radical synthesis inhibitors (allopurinol, magnesium) Free radical scavengers (Vit E) NOS inhibitors Anti-apoptotic agents