Neurological system Flashcards
Which cells form the BBB in the CNS?
Astrocytes
Which cells perform a phagocytic role in the CNS?
Microglia
Which cells produce myelin in the CNS?
Oligodendrocytes
Blood flow to the brain is via which 2 main arteries?
Internal carotid
Vertebral arteries
How many % of cardiac output does the brain receive?
10-15%
What 3 mechanisms control cerebral blood flow?
Autoregulation: Myogenic, metabolic
Neural
Local
What does autoregulation mean?
The brain maintaining about the same blood flow over a wide range of BPs
How does MYOGENIC autoregulation occur?
When cerebral blood vessels constrict/dilate to maintain adequate cerebral perfusion
BP rise = constrict
BP drop = dilate
Range of autoregulation of cerebral perfusion pressure (CPP)
60-160 mmHg
What happens at the extreme ends of CPP range?
50mmHg: cerebral blood vessels fail to maintain flow
150-160mmHg: fail to regulate flow, become abnormally permeable and causing cerebral oedema
Equation for cerebral perfusion pressure (CPP)
CPP = MAP - ICP
What happens when CPP falls <50mmHg?
Cerebral ischaemia
What happens when CPP falls <30mmHg?
Death
Factors impairing myogenic autoregulation
Ischaemia/hypoxia Trauma Cerebral haemorrhage Tumour Infection
How does METABOLIC autoregulation of cerebral blood flow (CBF) occur?
Increased brain activity = decreased PaO2 and increased PCO2 = local vasodilatation of cerebral blood vessels and increased perfusion
How does LOCAL autoregulation of CBF occur?
Changes in arterial PaO2 and CO2
Increase in CO2 = increase in CSF due to cerebral vasodilatation
Effect of changes in PaO2 not as marked - hypoxia only has a significant effect when it falls <8kPa
Factors affecting cerebral vessel response to PaO2 and PaCO2
Head injury
Cerebral haemorrhage
Shock
Hypoxia
Why is maintaining a low to normal PaCO2 level important in head injury patients?
To prevent increases in ICP due to cerebral vasodilatation
Where does CSF lie?
In subarachnoid space
Total CSF volume in brain
130-150mL (40mL in cerebral ventricles, 100mL around spinal cord)
Rate of CSF production
500mL per day
Normal CSF pressure
~0.5-1 kPa OR
10-15 mmHg
What produces CSF?
Ependymal cells in choroid plexus in the lateral, third and fourth ventricles (70%)
Blood vessels (30%)
Pathway of CSF flow within the CNS
Lateral ventricles –> interventricular foramina (of Munro) –> third ventricle –> cerebral aqueduct (of Sylvius) –> fourth ventricle –> foramen of Luschka (lateral) and Magendie (midline) –> subarachnoid space
What reabsorbs CSF back into the circulation?
Arachnoid villi/granulations –> project and drain into superior sagittal sinus
(small amt can be absorbed by spinal villi)
Composition of CSF
Glucose: 50-80mg/dl
Protein: 15-40 mg/dl
White blood cells: 0-3 cells/mm3
Red blood cells: NONE
Examples of focal and diffuse SOLs
Focal = tumour, aneurysm, blood/haematoma, granuloma, tuberculoma, cyst, abscess
Diffuse = vasodilatation, oedema
Consequences of intracranial SOLs
Raised ICP
Intracranial shift and herniation
Hydrocephalus
What is pressure within the cranium governed by?
The Monroe-Kelly doctrine = considers skull as a rigid closed box with brain, blood and CSF as only contents
Hence, ICP = V(csf) + V(brain) + V(blood)
Increases in mass can be accommodated by loss of CSF. Once a critical point is reached (usually 100-120ml of CSF lost) there can be no further compensation and ICP rises sharply.
Next step: pressure will begin to = MAP + neuronal death + herniation
Normal ICP in supine position
0-10mmHg (passmed: 7-15mmHg)
Consequences of raised ICP
Hydrocephalus
Cerebral ischaemia (any rise in ICP will eventually exceed autoregulation)
Brain shift and herniation
Systemic effects (thought to be due to autonomic imbalance, hypothalamic overactivity due to compression and ischaemia of vasomotor area)
Types of herniation
Transtentorial (lesion within 1 hemisphere causes herniation of medial part of temporal lobe over tentorium cerebelli)
Tonsillar (lesion in posterior fossa, lowest part of cerebellum pushes down into foramen magnum and compresses medulla)
Subfalcine (lesion in 1 hemisphere leads to herniation of cingulate gyrus under falx cerebri)
Diencephalic = coning (generalised brain swelling causing midbrain to herniate through the tentorium)
Systemic effects of raised ICP
Cushing’s reflex = decreased RR, bradycardia, HTN
Cushing’s ulcers
Neurogenic pulmonary oedema
Preterminal events = bilateral pupil constriction followed by dilation, tachycardia, decreased RR, hypotension
Clinical features of raised ICP
Headache
N+V
Papilloedema
Decreased consciousness
Clinical features of cerebral herniation
Transtentorial:
Oculomotor nerve compression = ipsilateral pupil dilation
Cerebral peduncles = contralateral hemiparesis
PCA = cortical blindness
Cerebral aqueduct = hydrocephalus
Tonsillar:
Compression of cardio/resp centres in medulla = death
Subfalcine: ACA = infarction
All types:
Reticular activating system = coma
Distortion of midbrain and tearing of vessels = death
What type of molecules can pass freely across the BBB into the interstitial space of the brain?
Lipid-soluble molecules
What does the BBB prevent?
Free movement of ions into the brain
Release of neurotransmitters from neurons into the peripheral circulation
What is the BBB formed by?
Structure of capillary endothelium with very tight cell-to-cell junctions
as opposed to the freely permeable fenestrated capillaries found in other tissues
End-feet of astrocytes also cover the basement membrane
Areas of the BBB containing fenestrated capillaries
Areas in the midline including:
3rd and 4th ventricles = allow drugs and noxious chemicals to trigger the chemoreceptor trigger zone in the floor of the 4th ventricle, which in turn triggers the vomiting centre. Angiotensin II also passes to the vasomotor centre in this region to increase sympathetic outflow and causes vasoconstriction of peripheral vessels
Posterior lobe of pituitary = allow release of ADH and oxytocin into circulation
Hypothalamus = allow release of releasing/inhibitory hormones into the portal-hypophyseal tract
Specific functions of BBB
Tight junctions restrict penetration of water-soluble substances
Lipid-soluble molecules e.g. CO2, O2, hormones, anaesthetics, alcohol can pass freely across
Endothelium has TRANSPORT PROTEINS (CARRIERS) for nutrients e.g. sugars, amino acids
Certain proteins e.g. insulin, albumin, may be transported by endocytosis and transcytosis
Preconditions for Dx of brainstem death
4 preconditions: Must be in a COMA Must be a KNOWN CAUSE for coma Cause must known to be IRREVERSIBLE Must be dependent on VENTILATOR
Exclusion criteria for Dx of brainstem death
No residual drug effects from narcotics, hypnotics, tranquilisers, muscle relaxants, alcohol, illicit drugs
Core body temp must be >35 deg
No circulatory, metabolic or endocrine abnormality disturbance that may contribute to the coma
Brainstem death tests
No direct/consensual pupillary response to light (CN 2-3)
Absent corneal reflex (CN 5 and 7)
No motor response in the CN distribution to stimuli in any somatic area (e.g. supraorbital or nailbed pressure leading to grimace)
No gag reflex (CN 9-10)
No cough reflex (CN 9-10)
No vestibulo-ocular reflex (CN 3, 6, 8)
Apnoea test
Must be done by 2 doctors (1 must be consultant) on 2 occasions, with >5 years’ experience and must be competent in the field (e.g. neuro/ITU), must not be part of transplant team
Types of nerve fibres
A-alpha A-beta A-gamma A-delta B C
Features of A-alpha fibre
Function = motor proprioception
Conduction velocity = 100m/s
Diameter = 15-20 micrometre
Features of A-delta fibre
Myelinated
Function = PAIN (initial sharp), temperature, touch
Conduction velocity = 20m/s
Diameter = 2-5 micrometre
Features of A-beta fibre
Function = touch, pressure
Conduction velocity = 50m/s
Diameter = 5-10 micrometre
Features of A-gamma fibre
“high intensity mechanical stimuli”
Function = motor proprioception
Conduction velocity = 30m/s
Diameter = 3-6 micrometre
Features of B fibre
Function = autonomic
Conduction velocity = 10m/s
Diameter = 3 micrometre
Features of C fibre
Unmyelinated "high intensity mechanothermal stimuli" Function = PAIN (dull, longer-lasting) Conduction velocity = 1m/s Diameter = 0.5-1 micrometre
Main types of neurotransmitters
Acetylcholine (excitatory)
Amines: catecholamines, 5-hydroxytryptamine (serotonin), histamine
Amino acids: glycine (inhibitory), glutamate (can be converted to GABA, excitatory or inhibitory), aspartate (excitatory)
Peptides: substance P (involved in pain transmission), endorphins (inhibit pain pathways)
Which amino acid are catecholamines formed from?
Tyrosine
Which enzymes degrade catecholamines?
Monoamine oxidase = breaks down NT taken up by PREsynaptic neuron
Catechol-O-methyl transferase = break down NT take up by POSTsynaptic neuron
Types of pain
Nociceptive (somatic, visceral) - common in surg pt
Referred - common in surg pt
Neuropathic
Psychogenic
Stages of pain transmission
Transduction
Transmission
Modulation
Perception
Inflammatory substances released after tissue damage
Prostaglandins Histamine Serotonin Bradykinin Substance P
Where do A-delta and C fibres synapse in the spinal cord?
Lamina I and III in the dorsal horn
What does the ‘gate control theory’ of Melzack and Wall in the modulation of pain propose?
That pain impulses received in the dorsal horn can be modulated by other descending spinal inputs
E.g. inhibitory inputs from periaqueductal gray matter and nucleus raphe magnus (both release serotonin) + locus coeruleus (release NA)
Plus release of naturally occurring enkephalins and endorphins
Effects of inadequate analgesia in surgical patients
Resp: increased chest wall splinting, reduced tidal volume, vital capacity and functional residual capacity, difficulty coughing, retention of secretions causing atelectasis and pneumonia
CV: increased HR and BP
Immobilisation, increased risk of VTE
Ileus
Urinary retention
Stress response
Psychological stress
Roles of different analgesic drugs at different stages of pain transmission
Transduction: paracetamol, NSAIDs
Transmission: LA, TENS
Modulation: opioids
MoA of paracetamol and NSAIDs
Inhibit prostaglandin production
Prostaglandin involved in sensitising nociceptive receptors in injured tissues to the effects of nociceptive compounds e.g. bradykinin, substance P
MoA of LA
Prevent conduction of APs in A-delta and C fibres
MoA of TENS
Stimulate A-beta fibres to inhibit pain transmission to higher centres
MoA of opioids
Bind to mu receptors in higher centres e.g. periaqueductal gray matter and nucleus raphe magnus = stimulate descending inhibitory inputs to pain perception
Bind to mu receptors in dorsal horn
Inhibit substance P release
Where do the preganglionic neurons of the parasympathetic nervous system lie?
In cranial nerve nuclei within the brainstem
Which CNs is parasympathetic output derived from?
CN 3, 7, 9, 10 Oculomotor Facial Glossopharyngeal Vagus
Which ganglia does the PNS feed into before being distributed to the structures it innervates?
CN III –> ciliary ganglion
CN VII –> sphenopalatine + submandibular ganglion
CN IX –> otic ganglion
S2-4 –> pelvic splanchnic nerve –> pelvic ganglion
Where do the preganglionic neurons of the sympathetic nervous system lie?
In the lateral horn of spinal grey matter
Where do the cell bodies of the postganglionic neurons of the sympathetic nervous system lie?
Either in the sympathetic chain OR
In a named plexus along the aorta (coeliac, superior and inferior mesenteric)
Management of patient with head injury transferred to ITU and acute rise in ICP
- Position the pt head up 30deg to improve venous drainage
(remove spinal collar only if safe) - Sedate the pt with propofol/thiopental (decrease cerebral metabolism)
- Hyperventilation
- Treat with IV mannitol (reduce brain water and volume)
- Induce hypothermia may be protective
- Contact neurosurgical team = may advise re-scaning of pt to identify reason for deterioration
- Surgical options = CSF drainage, haematoma evacuation, craniectomy, lobectomy
Why is paracetamol an effective analgesic and anti-pyretic but has poor anti-inflammatory action?
It inhibits COX-3 in the CNS causing analgesia
Little effect on COX-1 and 2 hence poor anti-inflammatory (which NSAIDs inhibit)
