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Energy Metabolism of the Brain. Cerebrospinal Fluid
František Duška
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Overview Brain metabolism Blood-brain barrier Cerebrospinal fluid
energy metabolism ammonia handling Blood-brain barrier Cerebrospinal fluid
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Brain metabolism (except neurotransmiter metabolism – next lecture)
Energy metabolism of the brain Ammonia handling
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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
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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
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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
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Functional imaging: PET
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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
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Ammonia handling in the brain
NH3 is a waste product of deamination reactions (GlnGlu, Glu2-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
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Ammonia handling Clinical consequences: liver disease impairs brain function principle: insufficient urea synthesis NH3 accumulationneurotoxicity Hepatic encephalopathy: gr.I-IV Fulminant liver failure (i.e. paracetamol poisoning) threatens live also by ICP
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Blood brain barrier
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Blood brain barrier History: Function:
19th century, Ehrlich: aniline dye i.v. stains all organs except brain 1960: morphology by electron microscope Function: BBB selectivity protects the brain
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Blood brain barrier Morphology: endothelium, BM, astrocyte
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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
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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
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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
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Cerebrospinal fluid Function and circulation
Collection and laboratory assessment
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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.)
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CSF normal composition
Metabolite CSF Serum Na+ 154 mM 140 mM Cl- 122 mM 103 mM HCO3- 22 mM 24mM Glucose 3,3 mM 5 mM Lactate 1.6 mM 1 mM Protein 0,35 g/l 70 g/l IgG 0,0018 g/l 12g/l CSF does not contain cells (normal: up to 5 WBC/l)
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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
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CSF in diagnostics CNS infection Degenerative diseases
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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