Transcript Metabolism of CNS, CSF

Energy Metabolism of the Brain.
Cerebrospinal Fluid
František Duška
Overview
• Brain metabolism
▫ energy metabolism
▫ ammonia handling
• Blood-brain barrier
• Cerebrospinal fluid
(except neurotransmiter metabolism – next lecture)
1. Energy metabolism of the brain
2. Ammonia handling
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
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
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
Functional imaging: PET
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
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
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
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
Blood brain barrier
• Morphology: endothelium, BM, astrocyte
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
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
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
1. Function and circulation
2. Collection and laboratory assessment
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.)
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)
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
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