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Energy Metabolism of the Brain. Cerebrospinal Fluid

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Presentation on theme: "Energy Metabolism of the Brain. Cerebrospinal Fluid"— Presentation transcript:

1 Energy Metabolism of the Brain. Cerebrospinal Fluid
František Duška

2 Overview Brain metabolism Blood-brain barrier Cerebrospinal fluid
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

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6 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

7 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

8 Functional imaging: PET

9 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

10 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

11 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

12 Blood brain barrier

13 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

14 Blood brain barrier Morphology: endothelium, BM, astrocyte

15 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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17 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

18 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

19 Cerebrospinal fluid Function and circulation
Collection and laboratory assessment

20 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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22 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)

23 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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25 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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