CNS Flashcards
Where in the brain does the hypothalamus lie?
Below the thalamus and ventrolaterally to the third ventricle.
From which embryological region of the brain does the hypothalamus develop from?
Diencephalon - prosencephalon
What proportion of the human brain mass does the hypothalamus occupy?
<1%
Name the four main anatomical regions of the hypothalamus. (x4)
- Caudal region = mammillary group
- Intermediate region = tuberal group
- Rostral region = chiasmatic group
- Supraoptic
- Preoptic
What makes up the mamillary group?
Mammillary bodies and posterior hypothalamic nuclei. MV are two rounded projections serving as a relay station for reflexes related to the sense of smell.
Describe the tuberal group.
The widest part, including the:
- Dorsomedial (DMH)
- Ventromedial (VMH)
- Lateral (LHA)
- Arcuate (ARC) nuclei
- Ventral extension forming the infundibulum, encircled by the median eminence (ME), distally expands to form the neural lobe of the hypophysis (pituitary gland).
Describe the Superoptic region.
Lies superior to the optic chiasm and contains:
- paraventricular (PVN),
- supraoptic (SON),
- anterior (AHN) and
- suprachiasmatic (SCN) nuclei
Axons from the PVN and SON form the HP tract, extending through the infundibulum to the posterior lobe of the pituitary.
Describe the preoptic region of the hypothalamus.
Anterior to the SON, regulates certain autonomic activities. It contains the medial and lateral preoptic nuclei and rostral periventricular nucleus (the thin region immediately adjacent to the third ventricular wall).
Where is the rostral perioptic nucleus found?
A thin region immediately adjacent to the third ventricular wall
What are the main functions of the hypothalamus?
- Control of the ANS - GI, bladder and heart rate
- Production of relseasing hormones, ADH and oxytocin
- Regulation of emotion and behaviour
- Regulation of hunger and thirst
- Control of body temperature
- Regulation of circadian rhythms and states of consciousness
What effect does stimulation of the posterior and lateral hypothalamus have on the ANS?
Increases arterial pressure and heart rate
Describe the different areas at which the hypothalamus releases hormones into the pituitary.
- Diffuses into portal system (x2 capillary beds) and deposited into the anterior pituitary
- Diffusing into the capillary plexus of the infundibular process posterior pituitary (neurohypophysis) - axons from SON and PVN
What afferent and efferent signals are processed and sent out by the:
- Mesencephalon
- Telencephalon
- Diencephalon
- Mesencephalon: Efferents backward and downward to the midbrain, reticular areas of the brainstem (RF)
- Telencephalon: Afferents from rhinencephalon, amygdala and globus pallidus of the basal ganglia; Efferents upward to the anterior thalamus and limbic portions of the cerebral cortex
- Diencephalon: Afferents from various thalamic nuclei; Efferents to the infundibulum
Stimulation of these areas of the hypothalamus can cause what changes in emotion and behaviour?
- LHA
- VMH
- Periventricular
- Most anterior and posterior most portions
- LHA - thirst and eating, increased general activity levels leading to overt rage and fighting.
- VMH - satiety, decreased eating and tranquillity.
- Periventricular region - leads to fear and punishment reactions.
- Anterior and posterior - stimulate sexual drive.
How does the hypothalamus control thirst?
Specific cells in the thirst centre of the LHA are stimulated by rising osmotic pressure of the extracellular fluid (ECF; fluid electrolytes here become too concentrated), causing the sensation of thirst.
Explain how the hypothalamus regulates circadian rhythm.
The SCN establishes patterns of awakening and sleep that occur on a circadian schedule (cycle of about 24 hours). It receives input from the eyes (retina) and sends output to other hypothalamic nuclei, the reticular formation [RF in the ascending reticular activating system (ARAS)], and pineal gland.
Name the sensory tract of the CNS associated with pain perception.
Spinothalamic
Name the sensory tracts of the CNS and what they are sensory for.
Where does wach tract decussate?
- Dorsal column - touch and pressure - decussates at midbrain
- Spinothalamic - pain - decussates at the level of the spinal cord
Name the three types of deep (true) pain.
- Chemical
- Mechanical
- Temperature
- Heat >45oC
- Cold <xoc></xoc>
Which type of sensory receptors are responsible for picking up and transmitting pain signals?
Name four subtypes.
Free Nerve endings
- A alpha
- A beta
- A delta
- C-fibres
Order the subtypes of free nerve endings in order of how fast they can transmit signals.
Which type is unmyelinated?
- A alpha - 72-120 m/s
- A beta - 36 - 72 m/s
- A delta - 4 - 36 m/s
- C-fibres - 0.4 - 2 m/s - unmyelinated
What is the role of inflammatory mediators in pain perception?
Inflammatory mediators are released from damaged tissue and can stimulate nociceptors directly.
Or they can also cause primary sensitisation by reducing the activation threshold of nociceptors so that the stimulation required to cause activation is less.
This type of nociceptor is lightly myelinated and responds to mechanical and thermal stimuli. They carry rapid, sharp pain and are responsible for the initial reflex response to acute pain.
A delta
This type of nociceptor is highly myelinated and has a low activation threshold, usually responding to light touch and transmiting nonnoxious stimuli.
A beta
This type of nociceptor is polymodal, responding to chemical, mechanical and thermal stimuli. Its activation leads to slow, burning pain.
C-fibres
Histologically the Dorsal Horn is divided into ten layers called….?
Rexed Laminae
Which layers of the Rexed Laminae do the pain pathways transmit to?
1 and 2
The Ventrolateral tract is made up of which two pain processing tracts?
Spinothalamic and Spinoreticular
Describe the root of the spinothalamic and spinoreticular tracts of the CNS.
- Spinothalamic - Decussates in SC, travels to the thalamus with a projection to the periaqueductal grey matter of midbrain.
- Spinoreticular - Decussates in SC, travels to the thalamus with a projection to the reticular formation.
Match the spinal tract with the type of pain signals it transmits:
- Spinothalamic
- Spinoreticular
- Pinprick
- True pain
Spinothalamic - Pinprick
Spinoreticular - True pain - most primitive tract
Which sensory tract, not found in humans, is sensory for touch, pain and “fleas”
Describe its route in the CNS.
Spinocervical
Decussates from the lateral cervical nucleus at the level of C2 and travels via the medial lemniscus to the thalamus.
What number of neurones are found in the sensory tracts of the CNS?
Three
Pain Gate Theory.
Explain
The idea that a non-noxious stimuli can be inhibitor to a noxious one when they are applied at the same time.
Technically - By activating Aβ fibres with tactile, non-noxious stimuli inhibitory interneurones in the dorsal horn are activated leading to inhibition of pain signals transmitted via C fibres
Think two people trying to get through a door at the same time.
Describe descending inhibition of pain pathways.
Periaquaductal grey matter and rostral ventromedial medulla contain lots of opioid and opioid receptors. Their decending pathways project into the dorsal horn and inhibit pain transmission.
They use serotonin and noradrenaline as NT.
Describe visceral pain stimuli.
(x4)
- Smooth muscle distension/ contraction
- Stretching of the organ capsule
- Ischaemia and necrosis
- Inflammatory mediators
What is referred pain?
Referred pain is pain experienced at a site distant from source of the pain.
It is due to the convergence of different afferents on to the same dorsal horn neurones in the spinal cord.
Allodynia
Pain due to a stimulus that does not normally provoke pain
Hyperalgesia
Increased pain from a stimulus that normally provokes pain
Describe the Lewvis triple response.
- Pain/itch
- Oedema
- Flare
Caused by somatic pain stimulation, histamine release from mast cells and the release of other inflammatory mediators in response to a noxious stimuli
What is meant by negative, neutral and positive energy balance?
Negative - less energy in than needed - weight loss
Neutral - balanced
Positive - more energy in than needed - weight gain
Outline the mechanism of action of Benzodiazapines
Name two drugs from this class
Potentiate the effects of GABA-gated chloride channels.
- Diazepam
- Midazolam
What are the pharmacokinetic features of Diazepam?
(ADME)
What are the side effects of its use?
- A – Dissolved in Propylene glycol and Na benzoate for injection. Very lipid soluble – poor IM absorption, rapid BBB crossing.
- D – Highly albumin bound (85%)
- M – Liver (one product is oxazepam – an appetite stimulant)
- E - Renal
Retrograde amnesia, Hepatic disease, Behavioural changes
How is Midazolam distributed in the body at acidic and alkaline pH?
Complete ADME for this drug.
Acidic = water soluble
Alkaline (ie in the body) it is lipid soluble and therefore crosses the BBB/ cell membranes easily.
- A – IM or IV
- D – Depends on pH.
- M – Cytochrome P450 - Hepatic
- E - Renal
Name a Benzadiazepine antagonist.
Flumazenil
Outline the mechanism of action of alpha-2 agonist sedatives.
Name three drugs from this class.
Agonist a2 receptors at presynaptic membranes reducing firing at Neurokinin post synaptic membranes by Substance P. Also facilitates glycine in the spinal cord.
- Xylazine
- Detomidine
- Medetomidine
Describe a side effect for each of these alpha-2 agonists:
- Xylazine
- Detomidine
- Medetomidine
- X - Cardio vascular suppression – some lack of selectivity at high doses
- D - Piloerection, penile prolapse, salvation, muscle tremors
- M - Alpha agonist effects
Acepromazine is a drug from which sedative class?
What is its MOA?
Phenothiazines
MOA - Block dopamine d2, a1 adrenergic and serotonergic receptors + others. D2 receptors found extensively in reticular formation
Which of these sedative classes has analgesic properties as well as sedation?
- Benzodiazapines
- alpha2 agonists
- Phenothiazines
Alpha2 agonists
Also butyrophenones (azaperone)
How do Butyrophenones act as antiemetics?
Blocking dopamine stimulation of the Chemoreceptor Trigger Zone which stimulates the vomit centre of the medulla.
The CTZ detects negative substances in the blood stimulating vommitting
What type of receptors are targetted by Local Anaesthetics?
What effects do LA’s have on these receptors?
Local anaesthetics are sodium channel blockers.
This short acting barbiturate should never be administered IM.
What is it used for?
PK data?
Pentobarbitone
- A – Oral, IV
- D - up to 50% protein bound
- M – Hepatic
- E – Renal
Side effects - narcotic excitement & agonal breathing
A long acting barbiturate used in the control of seisures.
PK Data
Side effects
Phenobarbitone
- A – Oral, IM, IV
- D - up to 50% protein bound
- M – Hepatic
- E – Renal and faecal
Side effects = sedation, respiratory depression, ataxia, PU/PD, polyphagia,
PK data for Thiopentone
(ADME)
- A – IV – painful;
- D – Very lipid soluble – causes unconsciousness in 30 – 45 secs. Rapid distribution throughout the body (5-10 minutes = offset). Redistributed to fat.
- M – Hepatic
- E – Renal
Name a non-barbiturate anaethetic agent.
Describe its method of action.
Propofol
- Potentiates GABAa receptors
- Sodium channel blocker
- Endocanabinoid agonist
What are the potential side effects of Ketamine.
- Retrograde amnesia,
- CV depression
- Respiratory depression
- Abnormal behaviour after recovery
- Muscle tension – must use with relaxation sedative (a2 agonists)
- Hypersalvation
- superficial sleep
- Raised intraoccular pressure
Name two neuroactive steroids and differentiate between their methods of action.
- Alfaxalone - Potentiates the effects of GABA at GABAa channels.
- Ketamine - Antagonist of glutamate at NMDA channels. Antagonist of mu opioid receptors and agonist of delta and kappa receptors
PK data for Ketamine
- A – IV, IM, oral and topical absorption due to it being lipid and water soluble. Undergoes first-pass metabolism with oral administration.
- M – Hepatic
- E – Metabolites are renally excreted
Which side effects of Halothane lead to the reduction in its use as a maintenance agent?
Teratogenic
Cerebellum circuitury
Deep cerebellar nuclei - inhibited by purkinje cells and stimulated by climbing fibres.
Parallel fibres - stimulated by mossy fibres
