205 NS - Biochemistry Flashcards
What does bloody CSF indicate?
Traumatic lumbar puncture
Subarachnoid haemorrhage
What does turbid/milky CSF indicate?
Presence of cells
Presence of microbes
Increased protein level
Presence of lipids (milky)
Where should lumbar puncture be done?
L3/L4 space or L4/L5 space
- because spinal cord ends at L2, avoid puncturing it
What can CSF analysis indicate?
CNS infections Demyelinating diseases CNS malignancy Hemorrhage in CNS Autoimmune disorders
How long should CSF analysis be done within?
Within 1 hour after sample collected
What does [glucose] in CSF depend on?
[glucose] in blood
rate of glucose transport into the CSF (efficiency of GLUT)
Metabolic rate of CNS
What is the glucose gradient along the neuraxis?
[Glucose] decreases from ventricular to lumbar fluid
What’s the function of CSF?
Protection
Buoyancy
Excretion of waste products
Regulation of cranial content volume
Excitatory neurotransmitters
Leads to depolarization
Glutamate
Aspartate
Serotonin
ATP
Inhibitory neurotransmitter
Leads to hyperpolarization
Glycine
GABA
Synthesis of acetylcholine
Choline + acetyl-CoA
Metabolism of acetylcholine
After released into synaptic cleft by exocytosis, hydrolyzed by acetylcholinesterase (AChE)
2 major constellations of cholinergic neurons
Basal forebrain constellation (sleep & wakefulness)
Dorsolateral pontine tegmental constellation (memory & learning)
What receptors mediate sympathetic effects?
Adrenergic
Exception: sweat gland (muscarinic)
What receptors mediate parasympathetic effects?
Muscarinic
Myasthenia Gravis
Autoimmune disorder
Leads to skeletal muscle weakness due to the development of autoantibody against AChR at NMJ
Synthesis of glutamate
Glutamine is synthesized to glutamate by glutamine synthetase (GS)
Metabolism of glutamate
Glutamate is broken down to glutamine by glutaminase (GA)
Excitotoxicity
Prolonged stimulation of neurons by excitatory a.p. results in neuronal death or injury
Synthesis of GABA (γ-aminobutyric acid)
Glutamate is synthesized to GABA by glutamic acid decarboxylase (GAD)
Metabolism of GABA (γ-aminobutyric acid)
After release, GABA is taken up into presynaptic terminal & glia
GABA is converted to glutamate by mitochondrial GABA transaminase (GABA-T)
What leads to epilepsy?
Lack of GABA in certain parts of brain
Which vitamin does glutamic acid decarboxylase (GAD) require?
Vitamin B6
Synthesis of catecholamines
Tyrosine → L-DOPA → dopamine
dopamine → norepinephrine
norepinephrine → epinephrine
Synthesis of dopamine
- Tyrosine enters neuron by active transport
- Tyrosine converted into DOPA by tyrosine hydroxylase
- DOPA converted to dopamine by DOPA decarboxylase
Metabolism of dopamine
Reuptake
Destroyed by COMT (catechol-O-methyltransferase) & MAO (monoamine oxidase)
What is used as index of function of dopaminergic neurons?
Homovanillic acid (HVA)
- because it’s a major metabolite that is produced by action of MAO and COMT on dopamine
Where are dopaminergic neurons located in the brain? (3)
Substantia nigra - coordination of movement, degeneration associated w Parkinson’s
Ventral tegmental area - pleasure & reward; motivation & emotion
Hypothalamic arcuate nucleus - regulate secretion of prolactin & maternal behavior
What causes schizophrenia?
Too much dopamine
What causes Parkinson’s disease?
Too little dopamine
Schizophrenia vs Parkinson’s disease
Schizophrenia - too much dopamine
Parkinson’s - too little dopamine
Cocaine drug addiction
The ventral tegmental area to limbic structures involve emotional reinforcement & motivation
Cocaine binds to dopamine transporter & blocks reuptake of dopamine → increased extracellular level of dopamine
Synthesis of norepinephrine
Dopamine β-hydroxylase (DBH) converts dopamine → norepinephrine
Synthesis of epinephrine
Phenylethanolamine N-Methyltransferase (PNMT) converts norepinephrine → epinephrine
Metabolism of norepinephrine & epinephrine
Same as dopamine:
Reuptake
Destroyed by COMT (catechol-O-methyltransferase) & MAO (monoamine oxidase)
Norepinephrine is involved in?
Sleep & wakefulness, attention, feeding behaviour
Mania
Too much norepinephrine
Depression
Too little norepinephrine
Norepinephrine & epinephrine are neurotransmitters of ______ system.
sympathetic
Synthesis of serotonin
- Tryptophan enters brain by active uptake
- Hydroxylated by tryptophan hydroxylase → 5-hydroxytryptophan
- Decarboxylated by aromatic a.a. decarboxylase → serotonin
Metabolism of serotonin
After release, serotonin reuptake by serotonin transporter or MAO
Serotonergic neurons
Raphe nuclei of medulla, pons, upper brainstem
- regulation of pain, mood, sleep
How does endorphin act as analgesic?
Endorphins are released by pituitary gland & hypothalamus to block pain perception
It binds to opiate receptors located on presynaptic membrane & block release of substance P - neurotransmitter involved in pain responses
Subarachnoid haemorrhage
Characterized by bleeding & pooling of blood between the innermost 2 membranes (arachnoid membrane & the pia mater)
Occur when bridging blood vessels/dural sinuses rupture
Most common cause of subarachnoid haemorrhage
Aneurysm
- when walls of blood vessels are weakened & dilates
What does fibrin clot in CSF sample indicate?
Protein level very high
How to differentiate bloody CSF sample of traumatic lumbar function of subarachnoid hemorrhage?
After centrifugation, observe supernatant
Clear → blood contamination
Yellowish → subarachnoid haemorrhage
