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Energy Metabolism of the Brain. Cerebrospinal Fluid

Energy Metabolism of the Brain. Cerebrospinal Fluid. František Duška. Overview. Brain metabolism energy metabolism ammonia handling Blood-brain barrier Cerebrospinal fluid. Brain metabolism. (except neurotransmiter metabolism – next lecture) Energy metabolism of the brain

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Energy Metabolism of the Brain. Cerebrospinal Fluid

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  1. Energy Metabolism of the Brain. Cerebrospinal Fluid František Duška

  2. Overview • Brain metabolism • energy metabolism • ammonia handling • Blood-brain barrier • Cerebrospinal fluid

  3. Brain metabolism (except neurotransmiter metabolism – next lecture) Energy metabolism of the brain Ammonia handling

  4. Energy metabolism of the brain • 2% of body weight, 20% of energy expenditure • GLUCOSE is the main fuel • daily consumption 120g • adopted starvation (3 weeks): oxidation of ketones in the brain covers up to 50% of energy

  5. What´s the first thing that happens when you think? • Excitatory firing  Glu uptake by glia  Na+ influx  ATP consumption by Na-K-ATPase  activation of glycolysis  lactate transported to neurons • Local increase in lactate increases blood flow • Excitotoxity = excesive Glu release • epilepsy, traumatic brain injury • Na+ and Ca2+ IC accumulation  swelling

  6. Functional imaging of ther brain • PET = positron emission tomography • 18F-2-deoxy-2-fluoroglucose • taken up by glia, phosphorylated but not further metabolized • active areas of the brain accumulate tracer

  7. Functional imaging: PET

  8. Oxygen uptake • Brain: 20% of whole-body O2 consumption • The most vulnerable to hypoxia • 5 min of VF/arrest may lead to irreversible brain damage • temperature dependent • Clinical use: • jugular venous oxymetry • tissue pO2

  9. Ammonia handling in the brain • NH3 is a waste product of deamination reactions (GlnGlu, Glu2-OG etc.) • Metabolism: • Glutamin synthetase: NH3 + Glu  Gln • Gln is metabolized in the liver/kidneys • Ammonia toxicity: NH3 + 2OG + NADH  Glu + NAD+ • Krebs cycle impairment: 2-OG depletion • Glu excess, excitotoxicity

  10. Ammonia handling • Clinical consequences: liver disease impairs brain function • principle: insufficient urea synthesis NH3 accumulationneurotoxicity • Hepatic encephalopathy: gr.I-IV • Fulminant liver failure (i.e. paracetamol poisoning) threatens live also by ICP

  11. Blood brain barrier

  12. Blood brain barrier • History: • 19th century, Ehrlich: aniline dye i.v. stains all organs except brain • 1960: morphology by electron microscope • Function: • BBB selectivity protects the brain

  13. Blood brain barrier • Morphology: endothelium, BM, astrocyte

  14. Blood brain barrier selectivity • Free permeability (passive diffusion): • small molecules: H2O, O2, CO2, NH3, ethanol • lipid soluble molecules: steroid hormones • Carrier mediated transport: • glucose: GLUT-1 (insulin independent) • amino acids • Pinocytosis

  15. Areas outside BBB • Enables brain to sense and regulate blood composition • Include: • Subfornical organ: osmoreceptors, regulate ADH • OVLT: dtto, thirst • Area postrema: chemoreceptors, vomining center

  16. BBB – clinical significance • CNS infection: • BBB protects against bacteria entry, but also antibodies and antibiotics • Kernikterus: • hyperbilirubinemia damages the brain in neonates but not in adults • Parkinsons disease: • =lack of dopamin in basal ganglia • cannot be treated with dopamin (does not cross BBB), but its precursor L-DOPA is useful

  17. Cerebrospinal fluid Function and circulation Collection and laboratory assessment

  18. Cerebrospinal fluid • Volume = 150 ml, daily production = 500ml • Function: • mechanical protection • distribution of neuroendocrine factors • „volume buffer“: helps to regulate ICP when tissue or intracranial blood volume rises (Monroe-Kelly doctrine: V-CSF+V-blood+V-brain tissue = const.)

  19. CSF normal composition CSF does not contain cells (normal: up to 5 WBC/l)

  20. CSF collection for dg. purposes • Lumbar puncture (rarely suboccipital puncture) • 4 samples (2 ml): • biochemistry: ions, Glc, lac, proteins incl. ELFO • cytology: No of RBC and WBC/l event. incl. differential count • bacteriology: standard culture and/or PCR • 1 backup sample stored at 4°C

  21. CSF in diagnostics • CNS infection • bacterial meningitis: voscous and opalescent CSF, WBC, Glucose,  Lac • viral meningitis: few cells,  protein • Degenerative diseases • oligoclonal bands in multiple sclerosis • others • Hematologic malignancy • leucemic cells infiltrate CNS

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