NEU Flashcards
Define:
Ataxia?
Proprioception?
Ataxia= A loss of control of bodily movements Proprioception= perception or awareness of the position and movement of the body
See spinal imaging analysis sheet
Example of spinal imaging
Main components of an intervertebral disc?
Centre: Nucleus pulposus
Around the outside: Fibrous ring
LABEL vertebra: Cranial articular facet? Dorsal spinous process? Caudal articular facet Intervertebral foramen? Nerve root outflow Transverse process? Part removed during facetectomy?
SEE image 1
SEE image 2
Labelled diagram of vertebral column?
SEE image 3
SEE image 4
Schematic of NS?
SEE image 5
Difference between somatic and autonomic NS?
Somatic NS= under voluntary control (cell bodies within CNS)
Autonomic NS= NOT under voluntary control
Components of CNS?
Brain
Spinal cord
Components of PNS?
Cranial nerves
Spinal nerves
Trunks of autonomous nerves
Enteric nervous system
(NOTE: PNS= projections out from CNS, everything that attached onto CNS)
Diagram of CNS and PNS positions?
SEE image 6
Components of nerve tissue?
Nerve cells (neurones) Supporting cells (glia cells/neuroglia)
NOTE: nerve cells produce network of interconnecting fibres which conduct within NS
BRAIN:
Grey and white matter?
GREY MATTER (around periphery, cell bodies):
- Perikarya of neurons (either superficial -> cortex OR embedded in white matter -> nuclei)
- Glial cells (produce myelin in white matter)
- Neuropil (felt of axonic, dendritic and glial processes)
WHITE MATTER (in centre, axons):
- Many myelinated processes
- Glia cells (produce myelin in white matter)
NOTE: perikaryon= neuron cell body
NOTE: glial cells have many processes and may line other structures e.g. blood vessels- SEE IMAGE 10
SEE IMAGE 7
SEE IMAGE 8
SEE IMAGE 9
SPINAL CORD:
Grey and white matter?
GREY MATTER (butterfly-shaped centre)
WHITE MATTER (on outside)
PNS
What are cranial nerves?
12 pairs of nerves Originate from brain, exit from brainstem
Cranium has got in the way of their segmentation
Label: front to back
Arranged in phylogenetic order: e.g. olfaction= c.n.I- reflects evolution of CNS (Olfactory nerve is at front of brain as sense of smell is first useful sense for unicellular organism THEN optic nerve to allow vision (first few nerves are in phylogenetic order) THEN movement of jaw THEN gill flap movement etc.)
SEE IMAGE 12
3 groups of cranial nerves:
- Purely sensory
- Purely motor
- Mixed
PNS
What are spinal nerves?
Nerves emerging from spinal cord
Come out between vertebrae through foramina
Connect CNS and rest of body
Explain fore/hind limb plexus?
Ventral branches of spinal nerves form plexus- innervation of limbs
Forelimb: brachial plexus
Hindlimb: lumbosacral plexus
NOTE:
Radial nerve is made up of components from C7 C8 and T1- mix of nerves which come out of brachial plexus to make up components of the major nerves
SEE IMAGE 13
PNS
Where are perikarya located?
In ganglia (groups of perikarya outside the CNS, inside PNS) In CNS (voluntary control) (in nuclei of cranial nerves or in ventral and lateral horn of the spinal cord)
SEE IMAGE 14
What are ganglia?
> Group of perikarya OUTSIDE of CNS, INSIDE of PNS > Can be site for: - Synapses (GVE - autonomic NS) - Cell bodies (general afferent) - General swapping of nerve fibres
NOTE: Exception= part of Vth cr.n. which has some of its sensory cell bodies in a nucleus rather than a PNS ganglion
OR
> Cyst filled with synovial fluid
SEE IMAGE 15
COMPLETE
27 and 28
Difference between cranial and spinal nerves?
Cranial:
Mostly with specialised functions
(Optic nerve- has only sensory fibres, hypoglossal nerve- only motor)
Spinal:
Mostly mixed fibres (motor AND sensory fibres)
2 parts of autonomous NS?
Complementary systems
1.) Sympathetic NS:
> THORACOLUMBAR= First neuron located in thoracolumbar spinal cord
> Sympathetic ganglia are either paravertebral (sympathetic chain) or prevertebral (celiac ganglion, cran. & caud. mesenteric ganglia, medulla of adrenal glands)
> Functions:
- Vasoconstriction= diverts blood away from GI tract/skin
- Increase blood flow to skeletal muscle
- Bronchiole dilation in lungs= greater oxygen exchange
- Increase HR/cardiac muscle contractility= mechanism for increase blood flow to skeletal muscles
- Pupil dilation/lens relaxation= more light enters eye
2.) Parasympathetic NS:
> CRANIO-SACRAL=
First neuron located in brainstem OR sacral spinal cord
> Nearer effector organ- tends to have ganglia at effector organs
> Functions:
- Blood vessel dilation leading to GI tract= increase bloodflow for digestion as (metabolic demands placed on body by gut) AND accelerates peristalsis
- Constricts bronchiolar diameter when oxygen demand decreases
- Constricts pupil/lens
- Genital erection
Functions of the NS?
1.) Uptake of information=
> From OUTSIDE:
- eyes/nose etc.
> From INSIDE:
- Proprioception (receptors in muscles/tendons)
- Enteroception (intestines etc.)
2.) Transport of information=
> Afferent fibres (periphery -> CNS)
> Efferent fibres (CNS -> periphery)
(NOTE: many different pathways within CNS)
3.) Processing of information
> Simple: reflex
> Most processing is more complex: behaviour
> Storage of info.: memory
NOTE: somatic= go to muscles, visceral= go to visceral (the gut)
Where are perikarya found?
Grey matter
Within ganglia
Functions of the NS?
1.) Uptake of information=
> From OUTSIDE:
- eyes/nose etc.
> From INSIDE:
- Proprioception (receptors in muscles/tendons)
- Enteroception (intestines etc.)
2.) Transport of information=
> Afferent fibres (periphery -> CNS)
> Efferent fibres (CNS -> periphery)
(NOTE: many different pathways within CNS)
3.) Processing of information
> Simple: reflex
> Most processing is more complex: behaviour
> Storage of info.: memory
NOTE: somatic= go to muscles, visceral= go to visceral (the gut)
NOTE: Cranial nerves may have 1/2/3 divisions of information whereas peripheral nerves may have 5/6/7
Structural divisions of the NS?
- PNS
Cranial nerves, spinal nerves - CNS
Brain, spinal cord
SEE IMAGE 16 - ENS
Controls rhythmic activity of GIT
Modified by autonomic NS
What are the groups of spinal nerves?
How are nerves named?
NOTE: in brackets= numbers of pairs in dogs
> Cervical (8)
- Due to C1 roots exiting through the atlas
- Means that C7 vertebra has C8 roots caudally.
> Thoracic (13)
- Labelled by the vertebra cranial to the root
Lumbar (7)
> Sacral (3)
> Caudal (c.4)
Naming:
Nerve is named by vertebra behind it EXCEPT for cervical region as C1 has 2 sets of routes
When do spinal nerves become part of the PNS?
Once spinal nerves have left the vertebral column, they are the PNS
COMPLETE
Typical components of spinal nerves?
Dorsal and ventral rootlets Dorsal and ventral rami Dorsal root ganglion Sympathetic ganglion SEE IMAGE 17
Neuroanatomy intro. SLIDES TO COMPLETE: 27 28 31 33 34 36 37 38 39
COMPLETE
Structural divisions of the NS?
- PNS
Cranial nerves, spinal nerves - CNS
Brain, spinal cord
SEE IMAGE 16 - ENS
Controls rhythmic activity of GIT
Modified by autonomic NS
SEE IMAGE 25
Spinal nerve components:
Explain the roots of spinal nerves?
(Dorsal and ventral- made from several rootlets)
> DORSAL
- Afferent
- Larger
- Contain dorsal root ganglion
> VENTRAL
- Efferent
NOTE: Unite near intervertebral foramen to make spinal nerve
SEE IMAGE 19
Spinal nerve components:
Explain the roots of spinal nerves?
(Dorsal and ventral- made from several rootlets)
> DORSAL
- Afferent
- Larger
- Contain dorsal root ganglion
> VENTRAL
- Efferent
NOTE: Roots unite near intervertebral foramen to make spinal nerve which branches into rami just outside intervertebral foramen
SEE IMAGE 19
Spinal nerve components:
Rami (branches)
Spinal nerve branched into rami just outside intervertebral foramen
DORSAL ramus: to ‘dorsal’ part of body
VENTRAL ramus: to ‘ventral’ part of body incl. limbs
Ventral= larger Both mixed (afferent and efferent)
SEE IMAGE 19
Spinal cord termination: Dog? Cat? Horse? Cattle?
What happens after spinal cord termination?
What is the space around nerves called?
Dog: L6/7
Cat: S3
Horse: S1
Cattle: L7
After this, the cauda equina fills the vertebral canal.
Space around the nerves= epidural space (LINK: epidural anaesthesia)
NOTE: outside spinal cord BUT inside bony spinal section
Where do cervical nerves exit?
How is this different to more caudal nerves?
What is the cauda equina?
What is the filum terminale?
Cervical nn: exit near intervertebral foramina
More caudal nn: have to travel down spinal canal before exiting.
(The bony column grows faster than the spinal cord)
Cauda equina:
Cauda equina region of spinal cord exits AS vertebral column is linger than spinal cord
After spinal cord ends, emergent spinal nerves travel down spinal canal as a group before emerging from their respective intervertebral foraminae
Bony part grows faster than spinal cord and as bone grows, drags nerves with it and so travel down inside of bony canal until they reach their exit through the foramina
e.g. follow 7: comes out earlier where spinal cord stops and then goes back in and exits further down where it should’ve exited= cauda equina forms as lots of nerve are doing this
Filum terminale:
End of meninges, continues into first few caudal vertebrae
Anchors bottom part of spinal cord
(‘Just a membrane part’)
NOTE:
Spinal cord segments are named by the foramen they exit from
SEE IMAGE 20
3 main sections of brain?
Cerebrum
Cerebellum
Brainstem
SEE IMAGE 21
More neurones in cerebellum or cerebrum?
More neurones in cerebellum than in cerebrum- relative size does not necessarily relate to number of neurones contained here
Main structures in brain cross-section?
Corpus callosum (only in mammals) Pituitary gland Inter-thalamic adhesion Pons (this is directly attached to pons) Medulla SEE DIAGRAM 22
Purpose of folds within the brain?
Increase brain SA
Fibre content of cranial nerves?
Mixed fibre content for different cranial nerves:
Motor (III, IV, V3, VI, VII, IX, X, XI, XII)
Sensory (I, II, V1, V2, V3, VII, VIII, IX, X)
Autonomic (PSNS: III, VII, IX, X)
(NOTE: there are variations, so this is a basic list)
Arranged segmentally, but constraints of the skull means the resultant physical pattern masks this
Cranial nerve function?
SEE IMAGE 23
ENS:
What is the smooth muscle of the GIT controlled by?
2 local nerve plexi control smooth muscle of GIT:
Meissner’s plexus: in submucosa
Auerbach’s plexus: between smooth mm layers
Operte autonomously: controls motility, local hormone reflexes
Modified by: autonomic NS
ENS:
Cross-section of gut schema?
SEE IMAGE 24
General neural structure:
Neurons?
Nueoglia?
Insulation?
Neurons= The actual conducting cells (functional units of NS) Neuroglia= Supporting/maintaining cells (outnumber neurons by 10:1) Insulation= Via lipid sheaths around inflow/outflow
Connective tissue in CNS?
No connective tissue in CNS:
- No obvious boundaries
- Blood vessels supported by neuroglia
(NOTE: connective tissue sheaths in PNS)
(NOTE: Nerves in the body are thicker than where they originated)
2 main types of neuroglial cells?
1.) MICROGLIA
> Specialised macrophages
> Mobile
> Control inflammation
2.) MACROGLIA > Oligodendrocytes - Insulators in CNS (learn) > Schwann cells - Insulators in PNS (learn) > Astrocytes - Control local environment of CNS > Satellite cells - Similar role to astrocytes > Ependymal cells - Make CSF and form blood-CSF barrier > Radial glia - Progenitor cells > Enteric glia - Found in GIT ganglia
Oligodendrocytes= 1 big cell and wrap around multiple cells and Schwann cells= long hotdog with multiple pieces of bread with nodes of ranvier being the spaces between these buns
Neurons: general structure?
COMPLETE SLIDE 9 NOTES SECTION
Large cells
Cell body (soma, perikaryon)
Processes (include one axon and one or more dendrites)
SEE IMAGE 26
3 main types of neuronal junctions?
- ) Synapses:
- Neuron-to-neuron
- Excitatory or inhibitory
- Only in grey matter - ) Neuromuscular junctions:
- Neuron-to-muscle cells
- Always excitatory in case of skeletal muscle - ) Neuroglandular junctions:
- Neuron-to-glandular cells
- Most secretory glands
SEE IMAGE 27
Polarity of neurones?
UNIPOLAR neurons
- (Pseudo-) unipolar- 1 process leaves cell body, then splits into 2:
- Structurally: resemble axons
- Functionally: 1 acts as axon, 1 acts as dendrite
- characteristic of general sensory neurons
- Cell bodies often grouped together in ganglia (collection of nerve cell bodies in PNS)
- Sensory neurones
BIPOLAR neurons
- 1 axon, 1 dendrite
- Fairly uncommon, mainly special sensory pathways (vision, taste, hearing, balance)
MULTIPOLAR neurons
- 1 axon, multiple dendrites
- Most numerous type
- Groups of such nerve cell bodies in CNS are termed nuclei
- Motor neurones
- Inter-neurones
Structural types of neurons?
AFFERENT (sensory):
Convey information towards CNS (i.e. info. is coming in)
EFFERENT (motor):
Convey information away from CNS
What are interneurons?
= association neurons
- Connect/associate 1 point with another in CNS BUT never leaves CNS
- Most numerous type of neuron
(e.g. link sensory and motor neurons together)
Divisions of NS 2 SLIDES TO COMPLETE: 5 6 8 10 13 14
COMPLETE
Functional components of PNS:
- ) Sensory?
- ) Motor?
1.) SENSORY: > GENERAL= - Somatic pain, temperature, touch (GSA) - Kinaethesia, proprioception (GSA) - Visceral sensation inc baroreceptors (GVA) > SPECIAL= - Vision & hearing (SSA) - Balance (SSA) - Taste & olfaction (SVA)
2.) MOTOR:
> GENERAL SKELETAL MUSCLES=
- Somatic efferent (GSE) – muscles of “somatic origin”
> GENERAL VISCERAL MUSCLES=
- *Autonomic - smooth muscle, cardiac muscle, glandular tissue (GVE)
> SPECIAL VISCERAL EFFERENT=
- Muscles derived from pharyngeal arches (SVE).
Composition of cranial nerves?
Cranial nerves:
General somatic afferent (GSA)
General visceral afferent (GVA)
Special somatic afferent (SSA)
Special visceral afferent (SVA)
General somatic efferent (GSE)
General visceral efferent (GVE)
Special visceral efferent (SVE)
What is the autonomic nervous system (ANS)?
= part of the PNS supplying efferent (motor) fibres to “visceral structures” i.e. GVE fibres
- Controls: intrinsic rhythms e.g. Cardic, Enteric
- Control centres in the CNS (medulla)
- Sympathetic
- Parasympathetic
(NOTE: Parasympathetic= controlled in different sections (e.g. heartrate and bladder are controlled independently (as organs usually) BUT sympathetic= controlled all as one (body ‘wakes up’)
Neurons: general structure?
COMPLETE SLIDE 9 NOTES SECTION
> Large cells
3 main regions:
a.) Cell body (soma, perikaryon)= receptive area
- Nutritional centre & large molecules production, impulse transmission
b.) 1 axon (process 1)
- Surrounded by Schwann cells
- Conduct impulse away from the cell body to axon terminals (transmission area)
c.) 1 or more dendrites (process 2.)= receptive area
- Receptive area for impulse transmission
SEE IMAGE 26 (2 parts)
What is the autonomic nervous system (ANS)?
= part of the PNS supplying efferent (motor) fibres to “visceral structures” i.e. GVE fibres
> CONTROLS: intrinsic rhythms e.g. Enteric
- Control centres in the CNS (medulla)
> SYMPATHETIC AND PARASYMPATHETIC (Opposite effects, but work in harmony not pure antagonism):
- Sympathetic=
* Spinal outflow T1 to L3
* General increase in alert state: Fear, flee, fright, fun & frolic
* Widespread effects
- Parasympathetic=
* Outflow in cr.n. 3,7,9,10 and sacral nn.
* Local control of action e.g.: Urination, salivary glands, GIT, heart rate.
.
(NOTE: Parasympathetic= controlled in different sections (e.g. heartrate and bladder are controlled independently (as organs usually) BUT sympathetic= controlled all as one (body ‘wakes up’)
SEE IMAGE 29
What 2 principal types of cells are the CNS and PNS composed of?
1.) Neurons
Produce and transmit the nerve impulse Present in the nerves
2.) Supporting cells Aid/assist the function of neurons
5-10 times more abundant than neurons especially in the brain
How are neurons classified by STRUCTURE?
= neurons are classified by structure: based on number of processes that extend from cell body
UNIPOLAR neurons
- (Pseudo-) unipolar- 1 process leaves cell body, then splits into 2 to cell body:
- Structurally: resemble axons
- Functionally: 1 acts as axon, 1 acts as dendrite
- characteristic of general sensory neurons
- Cell bodies often grouped together in ganglia (collection of nerve cell bodies in PNS)
- (Sensory neurons- One of the branched process receive sensory stimuli → nerve impulse delivering the signal to the CNS)
BIPOLAR neurons
- 1 axon, 1 dendrite
- Fairly uncommon, mainly special sensory pathways (vision, taste, hearing, balance)
- Found in retina, inner ear, brain (olfaction area only)
MULTIPOLAR neurons
- 1 axon, multiple dendrites
- Most common type
- Groups of such nerve cell bodies in CNS are termed nuclei
- May have different structure/shape based on their location in either the CNS or the PNS e.g. Pyramidal Cells (Cortex)
- (Motor neurons)
SEE IMAGE 28 (2 parts)
What are interneurons?
= association neurons
- Connect/associate 1 point with another in CNS BUT never leaves CNS
- Most numerous type of neuron
(e.g. link sensory and motor neurons together)
Cellular components in NS: nerve
Composition of nerves?
Composition of nerve fibres?
Nerve is composed of: Several bundles of nerve axons (nerve fibres) held together by connective tissue
Most nerves contain sensory AND motor fibres
Nerve fibre is composed of:
a. ) EPINEURIUM=
- Outermost, protective layer (strength)
- Consists of dense connective tissue, rich in collagen fibres
b. ) PERINEURIUM
- Surrounds each individual fascicle
- It is an epithelial layer that isolates bundle of axons from surrounding connective tissue
- Encloses fluid-filled space between perineurium and underlying nerve axons
- Connective tissue within perineural sheath= endoneurium
c. ) ENDONEURIUM
- Includes seams of loose connective tissue to provide pathways for small arterioles, venules and axons
SEE IMAGE 30
Where are NT’s/proteins proteins synthesised and how are they transported?
> Synthesised in cell body (Nissl bodies)
Transported via:
- Axoplasmic flow= contractions that push cytoplasm from axon hillock to nerve endings
- Axonal forward/retrograde transport= to/from nerve endings (via microtubules and kinesins, viruses & bacteria infecting the CNS take this route)
Neurons:
Axoplasm?
Axolemma?
Neurolemma?
Axoplasm= axon’s cytoplasm
Axolemma= axon’s membrane
Neurolemma= outer most layer of nerves fibres in the PNS. It is a cytoplasmic layer of Schwann cells that surround the multiple wrapping of myelin.
Neurons:
Axoplasm?
Axolemma?
Neurolemma?
Axoplasm= axon’s cytoplasm
Axolemma= axon’s membrane
Neurolemma= outer most layer of nerves fibres in the PNS. It is a cytoplasmic layer of Schwann cells that surround the multiple wrapping of myelin
How are neurons classified by FUNCTION?
SENSORY (AFFERENT) NEURONS:
Conduct impulses from sensory receptors INTO CNS
ASSOCIATION (INTERNEURONS):
Located in the CNS and serve the associative or integrative functions of the nervous system. They bridge sensory & motor neurons.
MOTOR (EFFERENT) NEURONS:
Conduct impulses OUT OF the CNS to effectors smooth m., cardiac m., skeletal m. & glands
How are neurons classified by FUNCTION?
SENSORY (AFFERENT) NEURONS:
- Conduct impulses from sensory receptors INTO CNS
- Mechano/chemo/thermo/ photo/electro/magneto/noci -ceptor (see other flaschard)
- SEE IMAGE 31
ASSOCIATION (INTERNEURONS):
- Located in the CNS
- Associative or integrative functions of the nervous system
- They bridge sensory & motor neurons:
Provide direct (reflex arcs) or indirect (via brain structures) connections between motor and sensory neurons AND between themselves
- Switch on or off the signal that is coming from outside
- SEE IMAGE 32
MOTOR (EFFERENT) NEURONS:
- Conduct impulses OUT OF the CNS to effectors smooth m., cardiac m., skeletal m. & glands
- Somatic motor neurons= reflex and voluntary control of skeletal muscle
- Autonomic motor neurons= innervate involuntary effectors smooth/cardiac m. & glands. The cell bodies are outside the CNS regrouped in ganglia. Autonomic neurons are also subdivided into sympathetic and parasympathetic (= autonomic NS)
Different types of sensory (afferent) neurons?
MECHANORECEPTOR:
Inner ear, muscles, tendons, large blood vessels & heart
CHEMORECEPTOR:
Mouth, nose, large blood vessels, brain
THERMORECEPTOR:
Skin and brain
PHOTORECEPTOR:
Eye
ELECTRORECEPTOR:
Skin (fish)
MAGNETORECEPTOR:
Eye (seems to be a kind of modified photoreceptor)
NOCIRECEPTOR:
Most parts of the body (sense the pain)
Which Supporting (glial) cells are in:
PNS?
CNS?
PNS:
Schwann cells
Satellite cells
CNS: Oligodendrocytes Astrocytes Microglia Ependymal cells
Explain supporting cells in PNS?
> SCHWANN CELLS:
- Schwann cells form myelin sheath around axons
- Each Schwann cell wrap ~1mm along the axon. Ranvier nodes between Schwann cells
- Myelin= electrical insulation and increases speed of impulse conduction (saltation). Allows impulse propagation over large distance without dissipation
> SATELLITE CELLS:
- Support functions (homeostasis) of neurons within the sensory and autonomic ganglia
- Can control the micro-environment of neurons
SEE IMAGE 32
Comparative speed of conduction:
Motor/sensory neurons?
Preganglionic?
Postganglionic?
Preganglionic= Fastest
Motor/sensory neurons= Middle
Postganglionic= Slowest
NOTE: axon diameter increase= increase conduction speed
What are ganglia?
Aggregations of neuron cell bodies outside of the CNS
These cell bodies are associated with pseudo-unipolar (somatic sensory) neurons and are located within dorsal root ganglions
The ganglion cells have centrally-located nuclei and a surrounding capsule, which consists of an inner portion of satellite cells
= Clusters of cells involved in autonomic nervous system
Explain supporting cells in CNS?
> OLIGODENDROCYTES:
- Form myelin sheath around axons
- Oligodendrocytes → white matter
- Cell bodies & dendrites → grey matter
> ASTROCYTES (filter everything travelling into nervous system):
- Help to form junction between capillaries and neurons
- They have processes that terminate in end-feet surrounding the capillaries of the CNS. The feet are involved in the formation of tight junctions between epithelial cells in capillaries
- Maintain ionic environment (have ion channels): buffer blood ionic concentration
- Take up some neurotransmitters released from the axon terminal of neurons and deliver them to neurons for re-use
- Involved in blood-brain barrier (NOTE: capillaries in brain only have tight junctions, NO gaps)
- Transform glucose from blood into lactate (lactic acid) which is released to neurons as energetic source for ATP production
> MICROGLIA:
- Phagocytose pathogens and cellular debris (immune system of brain/spinal cord)
- Relatively small, changing shape, oblong nuclei
- Found in all regions of brain/spinal cord
- Mobile in brain and multiply when brain is damaged
- In healthy CNS: microglia processes constantly sample environment (neurons, other supporting cells and blood vessels)
> EPENDYMAL CELLS:
- Line cavities (ventricles and central canal of spine) of CNS
- Produce CSF in ventricles by filtering blood from capillaries (Ependymal cells regulate glucose, amino acids (Cf. NTs) & ions level)
- Beat their cilia to help circulate the CSF (good circulation of CSF is crucial for nourishment of CNS)
Difference between oligodendrocytes and Schwann cells?
Schwann cells wrap 1 single axon, oligodendrocytes wrap several axons
BUT
They have similar properties with regard to nerve impulse (AP)
Function of CSF?
= liquid surrounding brain and spinal cord and fills spaces in them Supports brain
Lubricant
Maintains pressure in skull
Cushions shocks
Good circulation of CSF = crucial for nourishment of CNS
How is a signal transmitted between 2 neurons?
What is a synapse?
From presynaptic to postsynaptic cell via synaptic junction
Synapses= means the specific cellular areas participating in the nerve impulse transmission
SEE IMAGE 33 (2 parts)
Brain orientation terminology?
SEE IMAGE 34
Features of the brain: Sulcrus? White matter? Grey matter? Cerebral cortex (grey matter)? Gyrus? Fissure?
Gyrus= a ridge or fold between two clefts on the cerebral surface in the brain Sulcus= a shallower groove that surrounds a gyrus Fissure= a large furrow that divides the brain into lobes and also into the two hemispheres as the longitudinal fissure
SEE IMAGE 35
Structures of the brain: Right cerebral hemisphere Venous sinus Arachnoid villus Cerebellum Subarachnoid space Central canal 4th ventricle Aqueduct 3rd ventricle ?
SEE IMAGE 36
Development of the brain?
What are the main sections of the brain?
SEE IMAGE 37
Main sections of the brain=
Fore, mid and hind brain
Anatomical subdivisions of the brain?
SEE IMAGE 38
Are brain stem/hindbrain anatomical/functional divisions?
Brain stem= a functional division
Hindbrain= an anatomical division
What does the brainstem consist of?
Medulla oblongata
Pons
Midbrain/mesencephalon
SEE IMAGE 39
Slide 12
ECHO
Slide 14
COMPLETE
Brainstem- Medulla oblongata and pons:
Functions?
> Location of important regulatory centres:
-Respiratory
-Blood pressure
-Heart rate
Several cranial nerves emerge and have their nuclei here, many functions e.g. hearing, balance, swallowing, mimic musculature, masticatory musculature, salivation, parasympathetic
What does the hindbrain consist of?
Medulla oblongata
Pons
Cerebellum
What does the hindbrain consist of?
Medulla oblongata
Pons
Cerebellum
Brainstem- Mesencephalon/midbrain:
Parts of the midbrain?
- Tectum (four colliculi)
- Tegmentum (several nuclei)
- Crus cerebri (crura cerebri)
- Aqueductus mesencephali
NOTE: Colliculi= important in reflexes
Brainstem- Mesencephalon/midbrain:
Functions?
- Optic reflexes (rostral colliculi)
- Regulation of motor functions (head)
- Eye movement (visual reflexes)
- Arousal
What does the forebrain consist of?
TELENCEPHALON- hemispheres
(Cerebral cortex, basal ganglia, limbic system)
DIENCEPHALON- part of brain between the hemispheres
(Thalamus, hypothalamus, epithalamus)
SEE IMAGE 40
What is the diencephalon made up of?
Thalamus
Epithalamus
Hypothalamus: around 3rd ventricle
SEE IMAGE 41
What is the diencephalon made up of?
Function of these areas?
> Thalamus=
- Relay station for sensory info.
> Epithalamus
> Hypothalamus: around 3rd ventricle=
- Hormonal regulation
- Reproduction
- Appetite
- Flight/Fight
- Stress
SEE IMAGE 41
Interbrain
COMPLETE
Slide 22
What is the telencephalon made up of?
= cortex AND subcortical structures
> Cortex (divides into 3 types of cortex):
- Neocortex
- Archicortex
- Paleocortex
> Subcortical:
- e.g. basal ganglia
NOTE: neocortex= what is seen from the outside, subcortical structures are located much deeper in the brain
SEE IMAGE 42
Telencephalon continued
COMPLETE slide 26
TELENCEPHALON:
Function of the 3 layers of cortex?
> Paleocortex (paleopallium)=
Related to olfactory sense
TELENCEPHALON- 3 main types of cortex:
- ) Paleocortex (Palleopallium):
- What is it made up of?
- What is it’s function? - ) Archicortex
- What is it made up of?
- What is it’s function? - ) Neocortex
- What is it made up of?
- What is it’s function?
1.) Paleocortex (paleopallium)=
- Main areas: Olfactory bulb, olfactory tract
rostral commissure, piriform lobe
NOTE: piriform lobe= pear-shaped lob
SEE IMAGE 43 - Function: Related to olfactory sense
2. ) Archicortex (oldest part of the brain)= - Main areas:
Hippocampus and dentate gyrus
SEE IMAGE 44 - Function:
Memory generation- particularly spatial memory
3.) Neocortex (dominant part of cerebral cortex in mammals)=
- Main areas:
Corpus callosum?- check (corpus callosum= major connection between hemispheres)
SEE IMAGE 45
SEE IMAGE 46 - Function:
(Planning of) movement, perception, learning, memory
Slide 28- image
Slide 29- image and echo
Slide 31- image and echo
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s
s
Structure of the cortex?
Functions of the cortex?
Structure: SEE IMAGE …
Functions: Frontal lobe= motor cortex Parietal lobe= sensory cortex Temporal lobe= hearing Occipital lobe= vision
Summary of function: Principal structures= Cerebral cortex Basal ganglia Limbic system Thalamus Hypothalamus Tectum Tegmentum Cerebellum Pons Medulla oblongata Principal functions of these?
Cerebral cortex=
- (planning of) movement, perception, learning
Basal ganglia=
- coordination of movement
Limbic system=
- emotion, learning and memory
Thalamus=
- “switchboard” for neural input
Hypothalamus=
- appetite, reproduction, autonomic responses
Tectum Tegmentum=
- visual reflexes, audition
- sleep, arousal, pain, part of motor system
Cerebellum=
- integration and control of posture and movement
Pons=
- sleep, arousal
Medulla oblongata=
- heart rate, breathing, blood pressure
Structure of the cortex?
Functions of the cortex?
Structure:
SEE IMAGE 47
SEE IMAGE 48 (primary sensory and motor cortex, association cortex)
Functions: Frontal lobe= motor cortex Parietal lobe= sensory cortex Temporal lobe= hearing Occipital lobe= vision
NOTE: Sensory projections end up in visual cortex area
What is the Limbic System?
Not a ‘system’ as such- areas involved in major processes for survival (system involved in basic survival)
Functionally and anatomically connected but NOT all a system together
Hippocampus- involved in memory
Amygdala- involved in emotion e.g. happiness
Main areas invovled: the amygdala, hippocampus, thalamus, hypothalamus, basal ganglia, and cingulate gyrus
SEE IMAGE 49
Gross anatomy and function of the brain SLIDES TO COMPLETE: 12 14 18 22 26 28 29 31
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Gross anatomy and function of the brain SLIDES TO COMPLETE: 12 14 18 22 26 28 29 31
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What is behaviour?
Behavioural level of study?
Behaviour= Behaviour is the interaction between an organism and its environment that is based on the exchange of information between the two
Behavioural level= what you can observe (can also go into the genetic basis of behavior but not necessary yet)
What is ethology?
= Study of animal behaviour, but
also stands for a (sub)discipline in behavioural
sciences
What is anthropromorphism in this context?
Opposing our perception on how an animal works/how animal perceives environment/processors information AND projecting our own interpretation (e.g. how WE would react/think) onto an animal
Apply emotion to an animal
Can be negative BUT could be useful as increasing evidence that animals are cognitive (structures in behaviour which are not too dissimilar to humans)- gives some ideas to then follow up with scientific research
Main components environment can be classified into?
OWN BODY AS ENVIRONMENT
Living and non-living objects
SOCIAL ENVIRONMENT
(CONSPECIFIC)
Input -> Organism -> Output -> Act on environment (all 3 components)
SEE IMAGE 50
What is the three vector model of behaviour?
Input vector -> State vector (organism) -> Output vector
Three vector model of behaviour:
Explain input vector?
INPUT VECTOR=
- Senses and brain work together to interpret information coming from the environment- this complex process= input vector
- E.g. optical illusions: our mind tries to make sense of what we see
Three vector model of behaviour:
INPUT VECTOR: sign stimulus?
How can you predict the sign stimuli?
NOTE: Input is MORE than just light stimulus on retina- it is ALSO the behaviour that modifies the perception
INPUT VECTOR- SIGN STIMULUS=
- Key features of a stimulus that evokes a particular response (usually just small parts of environment- e.g. any trait of animal/plant/object)
- Describes simple features (red feathers) of complex stimulus (male robin) that bring about particular fixed action pattern
- Certain stimuli can induce/release a relatively invariable motor response or a relatively invariable complex motor behaviour
Predicting sign stiumuli: Know what sensory organs are used by an animal and you can predict the sign stimuli: - Visual cues (color, shape, and motion) - Chemical cues (“odor” and taste) - Sounds
EXAMPLE:
A male European robin in breeding condition
will attack a tuft of red feathers
placed in his territory.
NOTE: The fact that some stimuli are „easy“ to be processed („sign stimuli“) is an example how evolution shaped information processing in many species
e.g. larger egg will appear more ‘attractive’ to bird and so it will attempt to brood this instead of its own egg
Three vector model of behaviour:
Explain status vector?
What is neuroethology?
> Relevant status variables:
- Triangle of: Motivation Emotion Memory (Motivation etc..)
> Status variables
- Learning and memory
- Emotion
- Motivation
- Arousal
= processing, storage and modification/alteration of information
(ECHO BEHAVIOUR LECTURE TO UNDERSTAND FURTHER)
> Neuroethology:
Linking behaviour to activity pattern in the brain (e.g. bug detectors in frog are unresponsive to group of dots in field moving but can recognise one dot moving)
Three vector model of behaviour:
Explain output vector?
OUTPUT VECTOR=
- Describes elements of behaviour that are:
- generated by an animal
- accessible through observation
- Expression of particular behaviour can be species-specific
- E.g.: birdsong, locomotor behaviour
Analysing behaviour- Ethogram
Recording methods?
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Slide 51
Slide 52
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Slide 52, 53, 54
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Understanding behaviour:
Tinbergen’s four levels of behavioural explanation (“Four Whys”)?
Why?
Function (what is the behaviour for?)
Evolution (where does the behaviour come from?)
How?
Mechanism (how is the behaviour achieved?)
Development (how does the behaviour develop in ontogeny?)
NOTE: important to answer these questions to fully understand the behaviour
Understanding behaviour:
Different levels of explanation?
- ) Proximate explanations (How?)
- Relate to the mechanisms which bring about the expression of the behaviour:
* Physiology
* Aetiological factors - ) Ultimate explanations (Why?)
- Explain why proximate processes should arise:
* Function
* Adaptiveness
Instinct and drive in behaviour?
Instinct and drive are less relevant
Instinct is more out-dated now
Instinct is not needed and drive is less of a useful explanation
How can behaviour be measured?
Ethogram, spatio-temporal characteristics
Structure of behaviour- time?
Circadian rhythms
Sleep patterns
Structure of behaviour- biological rhythms:
- Definition?
- Chronobiology?
- Example?
Rhythm= a function which oscillates or cycles at a regular frequency
Biological rhythms= overt, measurable activities generated by some internal oscillator (or ‘clock’)
Chronobiology= a field of science that examines periodic (cyclic) phenomena in living organisms and their adaptation to external (environmental) rhythms
Example:
Circadian= A daily rhythmical change in behaviour or in a physiological process, such as sleep (melatonin increases during night-time) (NOTE: usually 24 hour cycle)
Structure of behaviour- biological rhythms:
- Definition?
- Chronobiology?
- Example?
Rhythm= a function which oscillates or cycles at a regular frequency
Biological rhythms= overt, measurable activities generated by some internal oscillator (or ‘clock’)
Chronobiology= a field of science that examines periodic (cyclic) phenomena in living organisms and their adaptation to external (environmental) rhythms
Example:
Circadian= A daily rhythmical change in behaviour or in a physiological process, such as sleep (melatonin increases during night-time) (NOTE: usually 24 hour cycle)
Examples of rhythms:
- Infradian
- Ultradian?
> Infradian:
- Rhythm with a period longer than the period of a circadian rhythm, i.e. with a frequency less than one cycle in 28 hours (cycle with a period which is longer than 24 hours)
- Example: reproduction cycles
- Example: Seasonal- SEE IMAGE 51
> Ultradian:
- Rhythms with period shorter than the period of a circadian rhythm - Example: REM (rapid eye movement) cycle in sleep
Structure of behaviour- time, biological rhythms:
Function of biological rhythms?
Zeitgeber meaning?
Biological clock are internal physical systems that enable organisms to live in harmony with rhythms of nature e.g. day/night/seasonal cycles
= EXTERNAL synchronisation
Circadian systems also maintain temporal organisation of endogenous processes
= INTERNAL synchronisation
Zeitgeber ("time giver", synchronizer)=
any external (exogenous) cue that entrains the internal (endogenous) time keeping system of organisms
Strongest Zeitgeber for plants/animals= light. Other examples= social interactions, pharmacological manipulation and eating/drinking patterns
Zeitgeber -> Entrainment -> Endogenous rhythm
The physiological basis of rhythms: Biological clocks
- Where?
1.) Retina – but no cones and rods required?
A photo pigment present in ganglion cells in the retina whose axons transmit information to the SCN, the thalamus, and the olivary pretectal nucleus
SEE IMAGE 52
2.) Suprachiasmatic nucleus (SCN) A nucleus situated atop the optic chiasm Contains a biological clock that is responsible for organizing many of the body’s circadian rhythms. SEE IMAGE 53 SEE IMAGE 54 (2 parts)
3.) Pineal gland:
Amino acid (tryptophan) derivative
Location= attached to dorsal tectum, immediately behind thalamus
Produces melatonin (hormone) and plays a role in circadian and seasonal rhythms by responding to light:
* More melatonin when dark (night)
* Less melatonin when light (day)
* Melatonin induces sleep (therapy?)- also other mechanisms involved in sleep
SEE IMAGE 55 (2 parts)
Circadian rhythms:
How is melatonin involved in short and long day breeders?
In long day breeders= represses reproduction
e.g. horse, fox, ferret (Spring)
In short day breeders=
stimulates reproduction
e.g. sheep, goat (Autumn)
How does light cause an affect on biological rhythms (i.e. biological clock)?
Light enters eye
Info. (light/dark) transferred from retina to SCN (biological clock)
SCN sends neuronal signals to pineal gland to secrete melatonin (high in dark)
NOTE: Melatonin also appears to be involved in synchronizing circadian rhythms.
Slide 24
ECHO
Summary of circadian rhythms?
Circadian timekeeping is a fundamental property of all higher forms of life
In mammals, the principal circadian mechanism lies in the individual neurones of the suprachiasmatic nucleus
Comparative studies of the clock in mammals and fruit flies have provided a model of autoregulatory feedback to explain its basic properties
The genes encoding this feedback loop, and how they and their protein products respond to synchronising cues, are being characterised
This opens the way for an understanding of how genes regulate a basic aspect of behaviour and what are suitable targets for intervention when this timing mechanism breaks down
Slide 4
EACH SINGLE MUSCLE FIBRE IS INNERVATED BY A SINGLE MOTOR-AXON.
CONTRACTION IS AN ALL OR NOTHING EVENT.
Therefore increased force generation is produced by recruiting more fibres (e.g. more fibres recruited to pick up a table than to pick up a book).
However a single motor-axon can innervate more than one muscle fibre
Axon fires= contraction (ALL OR NOTHING
What is a motor unit
A single α-motor neuron and all of the corresponding muscle fibres it innervates.
Two tissues that inter-dependent
Skeletal muscle MUST have axons going to it to function
SEE IMAGE
Single motorneuron & muscle fibers it innervates
Eye muscles – 1:1 muscle/nerve ratio
Hamstrings – 300:1 muscle/nerve ratio
In some cases thousands of fibres per axon
Most MU’s are quite small which gives gradation- recruit a lot of axons to recruit entire muscle
All fibres in a MU innervated simultaneously,
All same fibre-type.
MU size dictates level of control.
SEE IMAGE
MU properties
IMAGE
Distribution
Glycogen depletion method has shown that fibres belonging to the same MU can extend over a large area
Deep areas of a muscle tend to be redder and superficial areas paler
Can look at MU size by: Innervate specific axons and look at which muscle fibres the glycogen is depleted in
SEE IMAGE
Recruitment
Slow motor units tend to be smaller and during normal exercise tend to be recruited first.
Henneman’s size principle
This can be seen using electromyography (EMGs). During ballistic locomotion (e.g. jumping) faster MUs can be recruited initially (Henneman’s size principle is not used and so all of the fibres can be recruited at the same time) Generally: slow muscle fibres recruited first and then intermediate and then fastest Can look at fibre recruitment using myography
Slide 4
How are muscles innervated?
How is force generation increased?
Each single muscle fibre is innervated by single motor-axon
(However: a single motor-axon can innervate more than one muscle fibre)
Contraction= ALL OR NOTHING EVENT
SO
Recruiting more fibres= increased force generation produced (e.g. more fibres recruited to pick up a table than to pick up a book)
Most MU’s are quite small which gives gradation- recruit a lot of axons to recruit entire muscle
What is a motor unit?
= A single α-motor neuron and all of the corresponding muscle fibres it innervates
Two tissues that inter-dependent
SEE IMAGE 56
(NOTE: Skeletal muscle MUST have axons going to it to function)
All fibres in a MU innervated simultaneously,
All same fibre-type in MU
MU size dictates level of control
SEE IMAGE 57
Eye:
Muscle/nerve ratio?
Hamstrings:
Muscle/nerve ratio?
Eye muscles – 1:1 muscle/nerve ratio
Hamstrings – 300:1 muscle/nerve ratio
NOTE: can be thousands of fibres per axon
Properties of motor units?
SEE IMAGE 58
Explain distribution of MU’s?
How can MU size be examined?
Fibres belonging to the same MU can extend over a large area (Glycogen depletion method has shown this)
Deep areas of a muscle= redder Superficial areas= paler
Can look at MU size by: Innervate specific axons and look at which muscle fibres the glycogen is depleted in
SEE IMAGE 59
How are different motor units recruited during different levels of exercise?
> Slow motor units (usually):
- Smaller
- Recruited first during normal exercise
= Henneman’s size principle (under load, motor units are recruited from smallest to largest)- can see fibre recruitment using EMG’s
> During ballistic locomotion (e.g. jumping):
- Faster MUs can be recruited initially (Henneman’s size principle is not used and so all of the fibres can be recruited at the same time)
Generally: slow muscle fibres recruited first and then intermediate and then fastest
Neuromuscular junction diagram?
Function of calcium in this?
SEE IMAGE 60
SEE IMAGE 63
Level of calcium is usually higher on outside (in extracellular) than on inside SO VGC opens as AP travels down axon, allowing calcium to flood in
In this case it is NOT sarcoplasmic reticulum/sarcolemma. INSTEAD: floods into VGC and into axon and vesicles fuse with presynaptic membrane which releases acetylcholine (through exocytosis) and ach crosses to postsynaptic membrane, causing depolarisation of muscle fibre
SEE IMAGE
Difference between myopathy and neuropathy?
What can be used to distinguish between these? What is this based upon?
Why can it be difficult to distinguish between them?
Difference:
Myopathy= condition which is intrinsic to muscle itself
Neuropathy= intrinsic to nerves supplying the muscle
Used to distinguish between these:
The motor unit action potential (MUAP)
This is based upon size, shape and recruitment pattern.
Can be difficult to distinguish between them because:
they are so inter-connected
(NOTE: Electromyography can be used)
What is Electromyography (EMG)?
How does it work?
What can insertional and spontaneous activity indicate?
= a technique for evaluating properties of muscles at rest and while contracting.
- Electrodes (surface or needle electrodes) detect the electrical potential generated by active muscle cells (activity detected by electrodes as coming from particular muscles)
NOTE: Needle electrode preferable to study MUAPs preferable (goes into muscle tissue itself)
The insertional activity:
provides valuable information about the state of the muscle and its innervating nerve
Abnormal spontaneous activity (e.g. electrical activity being detected even when muscle is not active):
might indicate some nerve or muscle damage
EMGs and disease?
Laryngeal hemiplegia: can be used to detect neuropathy
NOTE: Insertional needle EMG can be used in laryngeal hemiplegia to study state of the myopathy
Cushing’s disease in horses: despite pronounced myopathy there is little change in EMG pattern
Can be used for some condition but not for others
How are muscle length and tension regulated?
How do antagonistic muscles work together?
Animal must be aware of muscle length/tension (automatic process)
Young: muscles and bones can get twisted if they are not aware
Adults: must be aware for coordination
Receptors in muscles:
> Muscle spindle=
- Detect dynamic and static changes in muscle length
- Stretch reflex (stretch on muscle causes reflex contraction)
> Golgi tendon organ (GTO)=
- Monitor tension developed in muscle
- Prevents damage during excessive force generation (stimulation results in reflex relaxation of muscle):
Muscle contraction -> puts tension on tendon -> sends sensory stimulus to spinal cord -> sends signal to muscle -> reduces tension (protects muscle and tendon)
SEE IMAGE 61
NOTE: Awareness of tension= protection mechanism (prevents damage)
SEE IMAGE 32 (relevant again under title ‘receptors in muscle’)
Neural input and output?
SEE IMAGE 62
For 50 muscle spindles, you’ have 100 motor nerve fibres
Muscle spindles are highly innervated compared to extrafusal muscle fibres
Golgi tendon organs have quite strong sensory impact
What is the basic structure of motivated behaviour?
Phase 1- Orientation
Phase II- Oriented
Phase III- Consumption
Flexibility/variability of behaviour decrease from phase I to phase III
Oriented behaviour= have a clue
‘Eating’ is used as an example here but it is not the only one
Travel to New York, hungry, search for cue which indicates a target (flexibility and variability of behaviour is quite high to start with before the cue is found e.g. may swap restaurants before finding mcdonalds BUT these decrease once the cue is found e.g. will go to mcdonalds once you have found it)
Seen in almost any animal
Stuck in hotel room and fixated on mcdonalds, once you get out your flexibility and variability will decrease as this is where you want to go
What is the basic structure of motivated behaviour?
Phase 1- Orientation
Phase II- Oriented
Phase III- Consumption
Flexibility/variability of behaviour decrease from phase I to phase III
EXAMPLE:
Oriented behaviour= have a clue
‘Eating’ is used as an example here but it is not the only one
Travel to New York, hungry, search for cue which indicates a target (flexibility and variability of behaviour is quite high to start with before the cue is found e.g. may swap restaurants before finding mcdonalds BUT these decrease once the cue is found e.g. will go to mcdonalds once you have found it)
Seen in almost any animal
Stuck in hotel room and fixated on mcdonalds, once you get out your flexibility and variability will decrease as this is where you want to go
NOTE:
There is feedback at any stage (feedback used to readjust motivation e.g. something wrong with the food -> go and eat somewhere else)
Motivation definition?
Internal decision-making process by which the animal chooses to perform a particular behaviour
(Chris Barnard)
Drive: Difficulties and Debates?
- No evidence for energy associated with motivational states in the CNS
- Little explanatory power: Saying, an animal feeds because of a hunger drive is circular
- Drives can be subdivided almost endlessly - little explanatory value
- Unitary drives (hunger, thirst) can incorporate a wide range of conditions
- Classical models omit feedback from the consequences of behaviour
- Response to a given drive affect also other aspects of internal state (e.g. feeding – thirst)
Internal stimuli in animal motivation?
Internal stimuli in animal motivation?
Weakness of these explanations?
External cues are particularly important: escape, aggression, predatory responses, exploration
Internal cues are particularly important: reproductive behaviour, ingestive behaviours
HOWEVER: this is a simplification – the contribution of internal and external cues varies: species and motivation dependent with individual differences occurring as well
Wallace Craig: Structure of motivated behaviour?
APPETITIVE:
Various initial motor patterns that bring the animal into a situation where it was likely to encounter a “stimulus”
(As if the animal had an “appetite for the stimulus”)
Phase I: No evidence of “stimulus” (e.g. prey): non-directed
Phase II: Stimulus detected (e.g. sight of prey), eventually capturing prey/ finding food: – directed
Phase III: Consummatory (killing prey, eating)
Phase IV: “Satiation” (=condition of being full to or beyond satisfaction)
CONSUMMATORY:
Stereotyped response to a stimulus
The performance of the behavior satisfies the animal’s “appetite”, the consumption of food satisfies a hunger
SEE IMAGE 64
Benefits of understanding motivation?
> Use motivations when training
> Knowing existing motivations can help
to:
- Facilitate desired behaviour
- Minimise undesired behaviour
Wallace Craig: Structure of motivated behaviour?
APPETITIVE:
Various initial motor patterns that bring the animal into a situation where it was likely to encounter a “stimulus”
(As if the animal had an “appetite for the stimulus”)
Phase I: No evidence of “stimulus” (e.g. prey): non-directed
Phase II: Stimulus detected (e.g. sight of prey), eventually capturing prey/ finding food: – directed
Phase III: Consummatory (killing prey, eating)
Phase IV: “Satiation” (=condition of being full to or beyond satisfaction)
CONSUMMATORY:
Stereotyped response to a stimulus
(The performance of the behaviour satisfies the animal’s “appetite”, e.g. the consumption of food satisfies a hunger)
SEE IMAGE 64
Which theory of motivation replaces previous explanations and why?
Often physiological causes for behaviour BUT precise relationship usually not known- can not assume particular physiological basis for motivation itself
= No direct, linear relationship between motivational state and behaviour
“State-space-approach” as a modern concept of motivation replaces homeostatic model
Homeostasis model of motivation?
Weakness of this model?
Homeostasis (Walter Cannon 1932):
“The coordinated physiological processes which maintain most of the steady states in the organism are so complex and so peculiar to living beings – involving, as they may, the brain and nerves, the heart, lungs, kidneys and spleen, all working cooperatively – that I have suggest a special designation for these states, homeostasis.”
BUT
- Homeostasis is not always a simple feedback process,does not simply imply constancy of the internal environment
- Feeding and drinking occur often in anticipation of physiological changes: Feedforward behaviour occurs, for example, drinking in rats and pigeons before starting to feed or in anticipation of thermally induced dehydration
Motivated behaviour: State space approach (McFarland)?
- Combined physiological and perceptual state (in the brain)= motivational state of the animal (= point in a motivational space)
- Not direct relationship between motivational state and behaviour
- Combines assumptions of homeostatic models with an explicitly functional approach to regulatory systems
Physiological impacts on behaviour BUT the relationship is not known
State-space models (McFarland and Sibly, 1975) represent an animal’s motivational state as an n-dimensional vector resulting from the interaction between internal and external factors (NOTE: motivation is affected by internal and external factors)
SEE IMAGE 65
Hunger as an example for motivational space- The hunger state exists within a
particular motivational space. Can break down hunger into what the hunger is for (i.e. fat/protein etc)
Set-point theory for ingestive behaviour (hunger)?
BUT
How does this explain obesity?
(Body can monitor blood glucose/body fat level)
Set-point theory:
Idea of homeostatic, negative feedback system regulating feeding
Two set points being regulated: Blood glucose (short-term regulation) body fat (long-term regulation)
Weakness of this= how can set point theory explain obesity?
Answer=
A settling point is a stable state caused by a balance of opposing forces, but without any setpoint or error detection (Regulated but at a higher point- set-point changes)
Brain concepts of motivation: The hypothalamic center model of Stellar?
Brain concepts of motivation: Areas involved in stimulating areas for eating in hypothalamus?
Potential consequences of lesion into hypothalamus?
Relationship between homeostatic and reward pathways?
Environment and mind against metabolic homeostasis?
SEE IMAGE 66
SEE IMAGE 67
Lesion into hypothalamus (effectively destroying it)= weight loss
SEE IMAGE 68
Reward pathway- wanting/liking something. In parallel with homeostatic pathway
Homeostatic mechanisms can be over-ridden by other mechanisms (e.g. reward pathway)
SEE IMAGE 69
SEE IMAGE 70
Explanation: Schematic flow diagram showing homeostatic regulatory system on left (dotted lines) and nonhomeostatic factors contributing to food intake and energy balance on right. The homeostatic regulatory system uses various short- and long-term feedback signals (e.g., leptin, CCK, and ghrelin) acting mainly on the brain to initiate adaptive behavioral, autonomic, and endocrine responses.
Labradors and appetite?
A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs
Motivation and emotion:
- ) POSITIVE emotions?
- ) NEGATIVE emotions?
NOTE: emotions can bring a stochastic element to motivated
behaviour
1.) POSITIVE emotions (approach):
> Related to “active” motivation- Facilitation of motivated behaviour
> Unrelated to “active” motivation
Interference with motivated behaviour (–> switch to other motivation?)
- ) NEGATIVE emotions
(aversions) :
> Related to “active” motivation
Interference with motivated behaviour
(–> switch to other motivation?)
> Unrelated to “active” motivation
Interference with motivated behaviour
(–> switch to other motivation?)
SUMMARY:
Positive emotions can facilitate OR interfere with motivational behaviour (e.g. interfere: another positive distraction may stop it from being motivated from the first, such as chasing a cat appearing more desirable than eating their food)
Drive and motivation?
It would seem that there are clear “drives” that motivate an organism to satisfy physiological needs. Such “drives” are referred to as homeostatic motivation. Drive-reduction theory attempted to quantify these drives
However, these do not explain all motivated behaviour. A number of non-homeostatic motivations exist and these may serve the purpose of maintaining arousal levels and filling time
Reflex arc?
SEE IMAGE 71 (2 parts)
Allows for automation of actions (action-reaction)
Basic reflex to maintain limbs in the same/correct posture
If you set muscle at one length then the muscles will try and maintain this length
Innervation of the reflex arc
1.) Type Ia fibres:
- Tend to form:
monosynaptic connection with alpha motor neurones
- (primary) Originate from:
annulospiral endings
-Produce impulses proportional to:
the rate of change of length of the intrafusal muscle fibres
- Produce: dynamic information
1.) Type II fibres:
- Tend to form:
polysynaptic responses
(Polysynaptic responses= more controlled/ coordinated BUT slower)
- (primary) Originate from:
flower spray nerve endings
-Produce impulses proportional to:
the tension within the intrafusal muscle fibres responding to change in length
- Produce: static information
NOTE: Predictable from size and speed of transmission of information
SEE IMAGE 72
What is proprioception?
= perception or awareness of the position and movement of the body
What is proprioception?
= System responsible for detecting changes in the position of the trunk, limbs and head
- Kinaesthesia
- Sense of joint position and movement
General principles of spinal cord organisation?
> Similar fibres arranged in tracts
> Afferent vs efferent regions
- SEE IMAGE 73
> Somatotopic organisation - Spatial orientation from receptor sites retained within fibre orientation within the tracts - Eg gracile and cuneate fasiculi - SEE IMAGE 74 (add in slide 16)
> Fibres run in white matter
- Fibres rarely run for more than 1 segment in grey matter
> Poly-synaptic
- Most pathways are polysynaptic- more than one neurone involved
- No afferent fibres reach the peripheral nerve without synapsing at least once
- Sensory fibres: all sensory information synapses at least once prior to projection into the cerebral cortex or cerebellum
> Decussation
> Sensible nomenclature
Species variations
What is proprioception?
= System responsible for detecting changes in the position of the trunk, limbs and head
- Kinaesthesia
- Sense of joint position and movement
- Can be conscious OR unconscious
General principles of spinal cord organisation?
> Similar fibres arranged in tracts
> Afferent vs efferent regions
- SEE IMAGE 73
> Somatotopic organisation - Spatial orientation from receptor sites retained within fibre orientation within the tracts - Eg gracile and cuneate fasiculi - SEE IMAGE 74 (add in slide 16)
> Fibres run in white matter
- Fibres rarely run for more than 1 segment in grey matter
> Poly-synaptic
- Most pathways are polysynaptic- more than one neurone involved
- No afferent fibres reach the peripheral nerve without synapsing at least once
- Sensory fibres: all sensory information synapses at least once prior to projection into the cerebral cortex or cerebellum
SEE IMAGE 75
> Decussation
> Sensible nomenclature
> Species variations
Reflex arc:
Receptors?
Muscle spindles Golgi tendon organs Joint capsule Ligaments Skin
Impact of cruciate injury/joint replacement on procprioception?
= loss of proprioception
General principles of spinal cord organisation?
> Similar fibres arranged in tracts
> Afferent vs efferent regions
- SEE IMAGE 73
> Somatotopic organisation - Spatial orientation from receptor sites retained within fibre orientation within the tracts - Eg gracile and cuneate fasiculi - SEE IMAGE 74 (add in slide 16)
> Fibres run in white matter
- Fibres rarely run for more than 1 segment in grey matter
> Poly-synaptic
- Most pathways are polysynaptic- more than one neurone involved
- No afferent fibres reach the peripheral nerve without synapsing at least once
- Sensory fibres: all sensory information synapses at least once prior to projection into the cerebral cortex or cerebellum
SEE IMAGE 75
(ALSO see other slides for explanation)
> Decussation
- Tracts passing into the cortex decussate at some stage to project contralaterally (opposite side of body)
- Tracts passing to the cerebellum tend to project ipselaterally (same side of body)
BUT everything that goes to consciousness cross over, things not to consciousness generally don’t
NOTE: some may not follow these roles
> Sensible nomenclature - Examples: * Spinothalamic= spine to thalamus * Spinocerebellar= spine to cerebellum * Rubrospinal= red nucleus (in brain) to spine
> Species variations
- Relative prominence of pyramidal system:
* Man= 30% of total white matter
* Dog= 10% of total white matter
- Sheep pyramidal system does not project beyond C4 segment
- Horse pyramidal system stops at C1
(Pyramidal system allows fine motor control of many muscles at the same time (horse doesn’t really need to move as it only has 1 stump of a digit, dogs have slightly more to be able to move digits))
NOTE: paw placement involves pyramidal AND extrapyramidal
Difference between conscious and unconscious proprioception?
Projection to cerebellum= unconscious
Projection to somesthetic cortex= conscious
Decussation of tracts: everything that goes to consciousness cross over, things not to consciousness generally don’t
Path of signals to coordinate proprioception- conscious and unconscious?
TO COMPLETE slide 29
Explain the Vestibulospinal tract?
> Does not obey all rules:
- Does not decussate
- Projects mainly to alpha motor neurones
- Strongly facilitatory (unlike most things that are inhibitory)
Afferent (sensory) pathways?
Touch, pressure – pass with conscious proprioception in the dorsal funiculus
Pain, temperature and touch – spinothalamic tract
What is the spinothalamic tract?
- Bilateral projection in domestic species
- Primary sensory fibre synapses in multiple segments
- Small fibres (some are unmyelinated)
- Species variation
SEE IMAGE 76
Basic principles of spinal radiography?
- Need atleast 2 orthogonal views
- Need anaesthesia/ at least heavy sedation to allow good positioning
- Need to avoid/consider parallax errors
- Appropriate exposure for region of interest
What are orthogonal views?
2 views at right angles to each other
e.g. Lateral AND ventrodorsal
Spinal cord imaging:
Ventrodorsal or dorsoventral?
Usually VD= better Because: - Vertebrae are closer to imaging plate - No movement blur from movement of chest cavity during respiration - Less magnification
NOTE: always remember marker (Lateral= cranial on left of screen, VD/DV= left of dog on right of screen- e.g. standing up and facing you)
Spinal radiography:
How should the spine be positioned relative to the plate and why?
SHOULD BE:
Straight and parallel to x-ray plate
BECAUSE:
X-rays all parallel to each other and so spine parallel to x-ray plate to allow beams to pass through intervertebral discs parallel to each other (allows comparison of discs)
SHOULD NOT BE:
a.) At oblique angle
BECAUSE:
fewer x-ray beams pass through the intervertebral discs
b.) Kyphosis/scoliosis
BECAUSE:
different information from spine at different points
SEE IMAGE 77 (3 parts)
Basic principles of spinal radiography?
- Need atleast 2 orthogonal views
SEE IMAGE 78 (2 parts) - Need anaesthesia/ at least heavy sedation to allow good positioning
- Need to avoid/consider parallax errors
SEE IMAGE 77 (3 parts) - Appropriate exposure for region of interest
What are orthogonal views?
2 views at right angles to each other
e.g. Lateral AND ventrodorsal
Spinal radiography:
How should the spine be positioned relative to the plate and why?
SHOULD BE:
Straight and parallel to x-ray plate
BECAUSE:
X-rays all parallel to each other and so spine parallel to x-ray plate to allow beams to pass through intervertebral discs parallel to each other (allows comparison of discs)
SHOULD NOT BE:
a.) At oblique angle
BECAUSE:
fewer x-ray beams pass through the intervertebral discs
b.) Kyphosis/scoliosis
BECAUSE:
different information from spine at different points
SEE IMAGE 77 (3 parts)
Spinal imaging:
Padding=
Why and how is padding used?
- Most dogs have wide pelvis/thorax and relatively wide head
- Spine sitting between and usually sags down- SO padding used
- Enables spine to be straightened and line up
- Under head/neck/pelvis/tail (species-variation)
SEE IMAGE 79 (2 parts)
Spinal cord imaging:
Ventrodorsal or dorsoventral?
Usually VD= better Because: - Vertebrae are closer to imaging plate - No movement blur from movement of chest cavity during respiration - Less magnification
NOTE: always remember marker (Lateral= cranial on left on screen, VD/DV= left of dog on right of screen- e.g. standing up and facing you)
Spinal imaging:
Should a radiograph of entire body of small body be taken to investigate the spine?
NOT IDEAL
X-rays generated from tube head as diverging beam (NOT as parallel x-rays)
Means: parallax error at each edge (difficult to interpret spaces between intervertebral discs) so only good quality image at centre of beam
Plate must be centred on x-ray beam and compare information round this centre- may need to take several images
SEE IMAGE 80
SEE IMAGE 81
Spinal radiography:
Axial rotation?
= PREVENT AXIAL ROTATION
Must be perpendicular
Different structures will over-lie each other (oblique view)
NOTE oblique view is sometimes needed
Lateral view: true lateral NOT rotated (difficult to compare 2 sides of vertebrae)
Padding used (stifle and chest- ensure line between sternum an dorsal spinous processes is parallel to x-ray table)
SEE IMAGE 82
What are dynamic views and why are they used?
- Animal must be still (static view) BUT sometimes take dynamic
- May be used in cases of suspected instability
Flexed endotracheal tube on R and head flexed down by 90 degrees
Moving animal creates different imamge
Opening up joint betwee axis and atals (atlantoaxial- peg)
Flexion view shows atlanto-axial instability_ BUT DO NOT force animal too much under anaesthetic as could paralyse the animal
Dynamic views- disarticulation, discolcation, subluxation in atlantoaxial joint in toy breeds
Open up intervertebral foramina between C1 and C2 by using R image (poen up)
BUT care not to traumatise spine using dynamic views (beware of spinal fracture)
Decide if fracture using catogram/dogogram before manipulating
SEE IMAGE 83
Spinal radiography:
Axial rotation?
How to check for axial rotation/lack of?
How to prevent axial rotation?
= PREVENT AXIAL ROTATION
> Checking for lack of axial rotation:
Perpendicular
Truly un-rotated= 2 rib heads overlying and 2 articular facet joints overlying each other (oblique view)
NOTE oblique view is sometimes needed
LOOK FOR: differences in space (e.g. intervertebral discs)- discs vary in size along spine so compare with discs either side of it
Preventing axial rotation:
Padding used- stifle and chest
Ensure line between sternum and dorsal spinous processes is parallel to x-ray table
SEE IMAGE 82
Myelography:
Injection sites for contrast?
1.) CISTERNAL puncture
Flex head down and insert needle between skull and C1 and inject contrast medium which flows down along cord
SEE IMAGE 84
2.) LUMBAR puncture
Inject contrast agent (needle sitting under spinal cord)White= contrast and has highlighted spinal cord9
Between L5 and L6 needle through interarcuate space, contrast mdium injected into subarachnoic space
Medium outlines spinal cord
SEE IMAGE 85
Contrast runs up and down around cord and outlines spinal cord
Can look at shape of spinal cord
Tramlines outline spinal cord to see changes
What are dynamic views?
Why are they used?
Precautions taken when using them?
- Animal must be still (static view) BUT moving animal creates different image
- May be used in cases of suspected instability
Example:
Flexed head downwards by 90 degrees- opens up intervertebral formaina between C1 and C2 (atlantoaxial joint) to show instability of joint
BUT
DO NOT force animal too much under anaesthetic as could paralyse the animal
NOTE: Beware of spinal fractures: use catogram/dogogram to check for fractures before manipulating
Can identify: disarticulation, disclocation, subluxation in atlantoaxial joint (especially in toy breeds)
SEE IMAGE 83 (2 parts)
Spinal imaging:
Explain myelography?
How does it correct a weakness of radiography?
- Contrast opacification of the sub-arachnoid space
- Non-ionic iodinated contrast medium (iodine-based contrast medium used for radiography)
- Put contrast into subarachnoid space (space between dura mater and spinal cord around spinal cord ) at the occipito-atlantal junction or caudal lumbar
Weakness of radiography:
Doesn’t show soft tissue associated with spinal cord and so may not allow diagnosis
Myelography:
Injection sites for contrast?
1.) CISTERNAL puncture
Flex head down and insert needle between skull and C1 and inject contrast medium which flows down along cord
SEE IMAGE 84
2.) LUMBAR puncture Inject contrast agent Between L5 and L6 needle through interarcuate space, contrast mdium injected into subarachnoic space Medium outlines spinal cord SEE IMAGE 85
Contrast runs up/down around cord and outlines spinal cord as tramlines to show shape of it
Myelography;
Sites for lesions (shown by contrast)?
Lesion outside dura mater?
Lesion within CSF space?
How do each of these lesions differ from normal when contrast is injected?
1.) Intramedullary (inside spinal cord)
2.) Extradural (outside dura)
3.) Intradural/ extramedullary (Within dura mater BUT not inside cord)
SEE IMAGE 86
Opacified space around cord so can see lesion within cord make it swell
Lesion outside dura mater= distorts/compresses column
Lesion within CSF space= compress spinal cord AND occlude space around the outside
> Normal= tramlines
Extra-dural (outside dura)= contrast column comes up and deviates around material
Intradural/ extramedullary (within dura but outside spinal cord)= contrast line goes around mass
Intra-medullary (within spinal cord)= spinal cord swells and lose contrast columns around each side (contrast may stop at lesion as it can’t go any further)
SEE IMAGE 87
What is MRI generally used for?
Superior soft tissue detail
MRI best for soft tissue (most of NS)
Alternate contrast studies to myelography?
Weakness of myelography?
What are all of these now generally surpassed by?
1.) Discography=
Direct injection into the intervertebral disc
2.) Epidurography
Opacification of the epidural space
> Weakness of myelography:
- Difficult to do- contrast in right place
- Difficult to interpret
- Abnormal material into subarachnoid space- can be fatal
All now generally surpassed by MRI
What is CT and when is it used?
CT/myelography vs MRI?
= Computed tomography
- Same information as routine radiography but slice detail (can use CT for everything radiography is used for)
- Can be combined with myelography to view details of spinal cord
> CT/myelography vs MRI
+ CT= useful where MRI not feasible (e.g. if metal implants present next to spine)
+ CT= better for viewing osseous structures
- CT and myelography= potentially fatal (unlike MRI)
What can be used in addition to CT to image the spinal cord in more detail?
CT and myelography can be combined= more info about spinal cord than CT by itself
Myelography allows space around spinal cord to be opacified
SEE IMAGE 88 (2 parts)
What is MRI generally used for?
Superior soft tissue detail (most of NS)
MRI conventions?
- Display conventions as for radiography
- Labelling for orientation produced at the time of imaging
MRI:
T1 vs T2?
SEE IMAGE 89
Bone Fat Fluid Soft tissue Gadolinium Pathology SEE IMAGE 90
MRI:
Explain the novel sequences and why they are used?
NOTE: 2 most commonly used outside of T1 and T2
- ) FLAIR=
- Suppresses signal from CSF (think fl is for fluid)
- Useful for lesions adjacent to ventricular structures (suppress signal from fluid within ventricles to see lesions)
- Helps to show up lesions in brain - ) STIR
- Suppresses fat signal
- Nerves in brachial plexus are surrounded by fat so STIR used to suppress fat signals so nerves can be visualised
What positive contrast agent is used in MRI and how does it work?
= Gadolinium
- Effectively high signal (white) on T1 weighted images
- Inject intravenously and goes around venous system (lights up venous blood on T1 images)
- Excluded by the blood brain barrier SO no change in brain)
- High vasculatory= goes white after contrast BUT no change in brain due to blood brain barrier SO if it goes white in brain then shows high vasculatory with no blood brain barrier
NOTE:
Radiography/CT= Looking where there isn’t contrast BUT gadolinium= looking for where there is contrast
What can MRI be used to detail?
DETAIL:
> Site of spinal cord compression
- SEE IMAGE 91
> AND significance of compression
- Spinal cord compressed at 2 sites (2 bulging discs) BUT white over 1 and not the other- T2 and so shows significance of 1 of these compression- oedema within spinal cord where is it white
- SEE IMAGE 92
> Lateralisation (cross-section)
- Need to know which side to make incision for surgery to remove material
- SEE IMAGE 93 (3 parts)
> Fibrocartilagenous embolisation
- High signal predominantly on LHS of spinal cord, discs adjacent to it are fairly normal
- Stroke within spinal cord
- Myelography would only show slight swelling of spinal cord
- SEE IMAGE 94 (2 parts)
> Trauma
- SEE IMAGE 95 (2 parts)
> Neoplasia
- Seen after contrast added, could not see on radiograph
SEE IMAGE 96 (2 parts)
-Tumour on Myelography vs MR (much easier on MR as myelogram is hard to distinguish between tumour and slipped disc in example)
SEE IMAGE 97 (2 parts)
SEE IMAGE 98
> Intraparenchymal neoplasia
- Tumour within spinal cord- MRI allows this to be localised
- Outlined by oedema all around it
- SEE IMAGE 99 (3 parts)
> Discospondylitis
- Infection (abscess) within disc
- Changes within bone also seen (not just soft tissue)
- SEE IMAGE 100 (2 parts)
> Transitional vertebra
- SEE IMAGE 101 (2 parts)
> Midline compression
- Different sites of compression
- Compression of spinal cord- shown by MRI
- SEE IMAGE 102 (4 parts)
> Asymptomatic
- Compression of spinal cord
- SEE IMAGE 103 (2 parts)
Spinal radiography:
What features of vertebrae can be identified on a radiograph?
Intervertebral disc space
Body
Transverse processes/ ribs
Dorsal spinous processes
Articular facettes
Spinal canal
Intervertebral foramina
Area surrounding vertebrae
(NOTE: be SYSTEMATIC= if lame on R forelimb, examine this leg last on a radiograph)
Spinal radiography:
What features of vertebrae can be identified on a radiograph?
Intervertebral disc space
Body
Transverse processes/ ribs
Dorsal spinous processes
Articular facettes
Spinal canal
Intervertebral foramina
Area surrounding vertebrae
(NOTE: be SYSTEMATIC= if lame on R forelimb, examine this leg last on a radiograph)
Ventral spinal/basilar artery?
Ventral spinal artery?
SEE IMAGE 118 (2 parts)
Explain blood supply TO the brain?
> Species variation- clinical relevance e.g. for slaughter
> Ventral
Explain blood supply TO the brain?
> Species variation- clinical relevance e.g. for slaughter
Arterial supply= ventral to brain
> Supplied by 5 main pairs of vessels
1.) ROSTRAL CEREBRAL ARTERIES=
supply the medial aspect of the cerebral hemispheres
2.) MIDDLE CEREBRAL ARTERIES=
supply the lateral and ventrolateral aspects of the cerebral hemispheres
3.) CAUDAL CEREBRAL ARTERIES=
supply the occipital lobes
4.) ROSTRAL CEREBELLAR ARTERIES=
supply the rostral aspects of the cerebellum
5.) CAUDAL CEREBELLAR ARTERIES=
supply the caudal and lateral aspects of the cerebellum
NOTE: all 5 pairs connect by/originate from the circle of WIllis (ventral to brain)
Explain the Circle of Willis?
- Ventral to brain
- Connect arteries supplying brain
- Structure:
- Rostral cerebral artery
- Middle cerebral artery
- Caudal cerebral artery
- Rostral cerebellar A
- Caudal cerebellar A, coming off- Basilar A
SEE IMAGE 119
Explain the Circle of Willis:
- Position?
- Function?
- Structure- blood going away FROM it
- Direction of blood flow?
- Structure- blood SUPPLYING it
- Ventral to brain
- Underneath hypothalamus
- Around pituitary gland
SEE IMAGE 119 - Connect arteries supplying brain
- Structure (blood going away from it):
- Rostral cerebral artery
- Middle cerebral artery
- Caudal cerebral artery
- Rostral cerebellar A
- Caudal cerebellar A, coming off- Basilar A
SEE IMAGE 120 - Direction of blood flow:
- From high to low pressure- either way around the circle
- Different species= different pressures= blood flows in different directions
- NOTE: if high pressure on left and low on right, blood flows on top clockwise, along the bottom anticlockwise
- Structure (blood supplying it):
- Internal carotid A (2)- comes from common carotid, which branches into ext. and int. carotid
- Basilar A- comes from spinal cord, changes name to ventral spinal A as it reach spinal cord
Explain origin of basilar artery?
Basilar artery= supply from spinal cord
As it reaches spinal cord: changes name to ventral spinal artery
Ventral spinal artery: supplied segmentally by vertebral artery- comes up and at every intervertebral foramina, artery comes in and connects to ventral spinal artery
SEE IMAGE 121
Vertebral artery: branch of subclavian artery, runs through vertebral foramina of C1 –C6 (close to bones), dives in at C6/C7 and runs underneath all of these muscles
Clinical implications of species variation of arterial supply to the brain?
Ritual slaughter – transection of external carotid artery and jugular veins
How long does it take for loss of consciousness due to reduced circulation?
May take up to 10 seconds for standing cattle to fall.
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Iliac thrombosis?
Thromboembolic disease affecting the descending aorta/iliac vessels Pain Pallour Paralysis Pulselessness
Clot that occludes descending aorta and … (ECHO)
Easy to diagnose (cold, no pulse and pain in hindlegs)
ECHO
Thrombus (clot) within descending aorta or iliac vessels
Thrombus in descending aorta: Back end of animal= avascular (pain, pallor, paralysis, no pulse in back legs). Back legs normal except no pulse in back legs
Iliac thrombosis (rare In dogs, common in cats)
Fibrocartilagenous embolisation(rare In cats, common in dogs)
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Venous drainage of spinal cord?
Slide 32, 33
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Slide 35
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Slide 39
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Slide 43
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Vasc.
Clinical implications of species variation of arterial supply to the brain?
Ritual slaughter – transection of external carotid artery and jugular veins
May take up to 10 seconds for standing cattle to fall due to reduced circulation
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Fibrocartilagenous embolisation?
SEE IMAGE 131
- Stroke within spinal cord
- Occurs at level of ascending artery OR after it has branched- to 1 side or the other
- Block blood supply to ascending artery= entire centre OR blocked after branching= only 1 side affected (oedema seen in LHS)
- Dog presents: hemiparesis if on one side
- Quick onset
Iliac thrombosis?
- Thromboembolic disease affecting the descending aorta/iliac vessels
- Pain
- Pallour
- Paralysis
- Pulselessness
- Easy to diagnose (cold, no pulse and pain in hindlegs)
- Thrombus (clot) within descending aorta or iliac vessels
- Thrombus in descending aorta: Back end of animal= avascular (pain, pallor, paralysis, no pulse in back legs). Back legs normal except no pulse in back legs
NOTE: Iliac thrombosis (rare In dogs, common in cats) Fibrocartilagenous embolisation (rare In cats, common in dogs)
Venous drainage of brain?
Communicating system of sinuses (instead of veins) > Sinuses: - Thin-walled - Poorly-developed/ absent valves - Bigger than veins
Three groups of sinuses:
Dorsal
Ventral
Connecting
(Connecting sinuses: join the other 2 groups together)
> Brachial plexus:
- Nerves forming the plexus?
- Location of the plexus?
- Nerves leaving the plexus? Nerves to the extrinsic muscles?
SEE IMAGE slide 9
Brachial plexus
Nerve supply from C6 to T2 is generally correct for most animals but natural variation means that this may shift in some people (i.e. may run C5 to T1 in some animals)
Each muscle is composed of series of segments embryologically and so segmental nerve supply (e.g. embryological form of muscle may have 2 segments and so require double innervation- 1 for each segment)- nerve supply to each embryological segment of a muscle
- The nerves forming the plexus=
C6-T2 (ventral rami) - Location=
in axilla
So in close contact with other axillary structures e.g. axillary a. v. and axillary lymph nodes - Main nerves leaving the plexus=
Nerves to extrinsic mm.
Nerves to intrinsic mm.
Extrinsic muscles keep limb attached to thorax
Synsarcosis= purely muscular attachment at a joint
Intrinsic muscles= protractors and retractors
Think of functional group of muscles as this then shows what the nerve supply is
Pectoral nerve supplies:
Pectoral group
Thoracodorsal nerve supplies:
Latissimus dorsi
Long thoracic nerve supplies:
Serratus ventralis thoracis
Lateral thoracic nerve supplies:
Cutaneous trunci
Several pectoral nerves represent several segments
Underlining= to help remember this table
Cutaneous trunci= makes the skin twitch (e.g. to get flies off an animal)- also used neurologically by vets, press gently with ballpoint pen and note reflex response
Suprascapular n. Subscapular nn. Axillary n. Radial n. Musculocutaneous n. Median n. Ulnar n.
Think of medan and ulnar nerves as same nerve, innervate very similar muscles BUT with different origins
(uLna = Lateral)
Venous drainage of the brain:
Describe the dorsal sinuses?
Rostral to caudal=
> Dorsal sagittal sinus:
- In falx cerebri centrally between cerebral cortices then caudally in skull
> Straight sinus:
- Drains great cerebral vein
> 2 transverse sinuses:
- Drains dorsal sagittal sinus
Caudal portion of dorsal sagittal sinus joins up with straight sinus and goes into skull. 2 transverse sinuses run down either side of skull (within skull) at level of junction between cerebellum and cerebral cortices. Caudally= within skull
SEE IMAGE 125
Venous drainage of the brain:
Describe the ventral sinuses?
> Dorsal and ventral petrosal sinuses
- Connect caudally with transverse sinus
> Cavernous sinus - A median connecting pair of sinuses - Sits around pituitary gland - Inside sinus= retus mirabile for arteriole supply, around outside of this= Circle of Willis SEE IMAGE 126
Venous drainage of the brain:
Describe the connecting sinuses?
- Join things up between cerebral and spinal sinuses
- Extracranial connection to maxillary vein- everything drains caudally into maxillary vein
Venous drainage of the brain:
Role of maxillary vein
Dorsal and ventral sinuses run caudally
Join together and drain into maxillary vein
SEE IMAGE 127
How does the venous drainage leave the brain?
- High pressure to low pressure
- Either:
a. ) Connect and leave via maxillary vein
b. ) Go along spinal cord as venous ventral spinal sinuses
Venous drainage of the brain:
Summary diagram?
SEE IMAGE 128
Clinical relevance:
Are you able to ligate the sagittal sinus?
Ligation of sagittal sinus= leads to fatal cerebral oedema
BUT
can ligate 1 transverse sinus (have to operate inside venous sinus and damage in this area could cause large amounts of bleeding)
NOTE: Surgical approach to the pituitary is risky
What is the blood brain barrier?
= selective barrier for exchange of substances between circulating blood (arterial and venous blood) and the parenchyma of the nervous system
Located at capillary level
Not all of brain has intact blood brain barrier
Capillary wall structure of the blood brain barrier?
(Bottom to top) > Lumen of vessel > Endothlium - Tight junctions between endothelial cells (prevent paracellular flux), overlapping endothelium > Basement membrane - Thick > Astrocytes - Put down little processes, astrocytes line whole capillary system within brain > Extracellular space SEE IMAGE 129 SEE IMAGE 132
NOTE: very tight, NOT leaky as elsewhere in body
Which substances are able to/NOT able to cross the blood brain barrier?
Methods of crossing barrier?
> Able to cross:
- Sometimes smaller molecules
- Lipid soluble
> NOT able to cross:
- Large molecules
- Glucose (requires active transport to pass into extracellular fluid/CSF)
> Methods:
- Active transport
- Pinocytosis
- P-glycoprotein pumps actively eject undesired substances.
Which parts of the brain do not have intact blood brain barrier and why?
Not all of the brain has an intact blood brain barrier
- Pituitary gland=
Large organic molecules produced here need to get out into circulation - Choroid Plexus=
Produces CSF
NOTE: both become more white/brighter after staining
SEE IMAGE 130 (6 parts)
Clinical significance of blood brain barrier?
Separation of brain from blood
Large macromolecules and non-lipid soluble drugs will be excluded from the brain
(Barrier to pathogens BUT also barrier to certain drugs used)
Role of the Choroid Plexus?
Produces cerebrospinal fluid
Free
Free
Free
Free
Vascular system SLIDES TO COMPLETE: 13 14 15 16 17 18 19 20 21 22 24 25 26 32 33
Complete these
Neuronal diseases and their causes?
a.) Neuronal diseases:
> Meningitis
= Inflammation of the meninges
> Encephalitis
= Inflammation of the brain
> Meningoencephalitis
= Simultaneous inflammation of the meninges AND the brain
b.) Causes:
Bacteria, viruses, fungi, protozoa, Rickettsia, parasite migrations, chemical agents, and idiopathic or immune-mediated diseases.
What does idiopathic mean?
Disease/condition arising spontaneously or with unknown cause
How can microbial pathogens damage the nervous system?
- ) Invasion and replication in the tissues:
- Direct invasion of peripheral nerves
- From adjacent structures such as from the meninges
- From the blood Haematogenous - ) Inducing an immune response:
- Inflammation of CNS
- Damage caused by local inflammation to the CNS
- Auto-immune response. Human example Guillain–Barré syndrome due to Campylobacter - ) Releasing toxins:
- Block signalling
- Damage specific cells
Neuronal diseases and their causes?
Explain their prevalence?
a.) Neuronal diseases:
> Meningitis
= Inflammation of the meninges
> Encephalitis
= Inflammation of the brain
> Meningoencephalitis
= Simultaneous inflammation of the meninges AND the brain
b.) Causes:
Bacteria, viruses, fungi, protozoa, Rickettsia, parasite migrations, chemical agents, and idiopathic or immune-mediated diseases.
- Prevalence
Fairly uncommon
BBB: nerous tissue is enclosed and CNS is maintained sterile
To cause disease the organisms, toxins need to access the CNS
NOTE: For antibiotics to be effective they need to reach the right concentration in the CNS. Therefore selection on a drug with the relevant destruction can be very important.
Pathogen spread and access to the CNS?
Entry to body -> Spread -> a.) Neurotropic (from peripheral nerves - nerve to nerve)
OR
b.) Neural Abscess
(from a septic focus)
OR
c.) Haematogenous
(via blood)
COMPLETE THIS SLIDE 6
Function of cutaneous trunci?
Cutaneous trunci= Makes the skin twitch (e.g. to get flies off an animal)- also used neurologically by vets, press gently with ballpoint pen and note reflex response
Why does haematogenous spread pose a risk to CNS?
Infectious agents in blood can get deep into tissue
Sticks to blood vessel wall and gets into neurological tissue
How can the blood brain barrier be breached?
NEED TO COMPLETE THIS- ECHO
a. ) Transcellular
- Pathogens bind host cells and invade through the cell (i.e. binds to membrane, uptake into cell)
- Passive or active on the part of the pathogen
- Transcellular common pathogen examples:
* Bacterial= Streptococci, Listeria sp.
* Fungal= Candida (yeast), Cryptococcus (dia-morphihic fungus)
b. ) Paracellular
- Tight junctions dramatically change or new routes open
- Increased pinocytic activity leading to trans-endothlial channels formation or tight junction function can be broken
- Paracellular common pathogen examples:
* Nipah virus (Malaysia-Porcine respiratory and encephalitis syndrome).
* Lyme disease (bacterial) - Borrelia burgodorferi a spirochete.
c.) Intracellular within leucocytes (Torjan horse)
- Requires primary infection
- Spreads where cell goes
- May be refractive to antibody once established (if it spreads cell-to-cell)
- Intracellular transmigration pathogen examples:
Examples intracellular transmigration:
* SIV/ HIV
* Canine distemper
NOTE: In addition to these breaches, overgrowth and necrosis can cause indiscriminate damage to tissue
NOTE: Some organisms can also enter by different routes
SLIDE 13
COMPLETE
Pathogens can trigger inflammation: what are the consequences of this?
NOTE: Non specific inflammation can be caused by attracted leucocytes
Impacts neuronal tissue (can be indirect: pressure from attracted cells)
Clinical signs of CNS infection?
Depression Pyrexia Cervical pain Hyperaesthesia Photophobia Generalized rigidity Seizures Paralysis local and general Ataxia Papilloedema Possible ophthalmic inflammation. Systemic signs. Septic shock and brachycardia.
Try to localise, can be associated with many things
Look at COMBINATION of clinical signs
How can microbiology of CNS be assessed?
Joint-tap- take fluid from joints or CNS
CNS should be maintained sterile- pathogens need to enter CNS to cause dosease
Infection indicators?
Slide 17
Example of pathogens which can infect the CNS?
General specific infection: bacteria in blood impacts across the body
Spread of an organism in blood that starts in sepctic foci in nervous tissue
Example of pathogens which can infect the CNS?
General specific infection: bacteria in blood impacts across the body
Spread of an organism in blood that starts in septic foci in nervous tissue
Examples of pathogens which can infect the CNS?
> Canine distemper
(viraemia/haematogenous/broad infection)
> Listeria
(neurotropic spread-bacterial)
> Rabies
(neurotropic spread-viral)
NOTE: need to know organism, basic details of infection
What is Canine Distemper Virus?
- Infectious disease of dogs and other carnivores
- Pantropic – generalised infection in many organ systems as the receptors are common on many cells
- Spread: close contact or by aerosols infect via URT then go systemic
How is canine distemper virus spread?
- Primary infection site= mucosal surface
- Virus replicates in URT
- Spreads to tonsils and bronchial lymph nodes
- Viral replication leads to lymphocytolysis / leukopenia- Allowing viraemia
- Dissemination to other sites: including GIT, Urinary, and CNS tissue (can cross blood brain barrier)
- NOTE: Can spread neuron to neuron without cytolysis
SEE IMAGE 133
How is Listeria spread?
Listeria attaches to and enters mammalian cells
This attachment induces phagocytosis
Listeria release themselves from the vacuoles with listeriolysin
Move in cells and between cells by nucleating actin
Hence they can spread is neurotropic (nerve cell to nerve cell)
Listeria in ruminants?
Listeria found in the environment.
Outbreaks tend to be seasonal.
They can an replicate in poor quality silages pH above 5.5.
In good quality silage multiplication is inhibited by acid pH
In ruminants may present as encephalitis, abortion, septicaemia, or endophthalmitis
One source of susceptibility is decreased cell-mediated immunity associated with advanced pregnancy
Listeria:
Clinical signs?
Treatment?
Prevention?
Clinical signs (cattle from ocular infection)
Incubation period of neural Listeriosis ranges from 14 to 40 days.
Dullness, circling and tilting of head facial paralysis.
Unilateral facial paralysis can result in drooling and dropping of eyelids and ears.
Treatment
In early stages with antibiotics
Prevention
Do Not feed poor silage to pregnant ruminants.
Do not feed poor quality silage at all?!
Ensure feed method used reduces ocular contact.
Vaccines do NOT work as the pathogen is intracellular
What is Rabies?
RNA virus
Rod shaped
Enveloped
How is rabies spread?
- Variety of reservoirs (most common animal reservoir= bats)
- Present in infected carnivore’s saliva
- Bite proximal leg
- Virus replicates in muscles
- Virus reaches sensory/motor nerve ends
- Binds acetylcholine receptor (or other sensory end receptors)
- Virus enters distal reaches of nerves and begins second stage of infection
- Neuronal infection with centripetal passive movement within axons
(“retrograde axoplasmic flow”) - Reaches CNS (spinal cord initially)
- Virus reaches limbic system of brain and replicates extensively here (leads to the aberrant behaviour) (“furious rabies”)
- Spread continues clinical replication in cortex (“dumb rabies”)- Cell pathology low, but cells all contain virus.
- Centrifugal spread to periphery: organs, salivary glands where virus buds from cytoplasmic membrane different from nerves
Fungi that can cause neurological infection?
> NOTE: fungal infections of CNS= fairly uncommon in dogs/cats (more common in warm, humid conditions)
> Fungi that can cause neurological infection:
Cryptococcus neoformans (dimorphic yeast) Can infect cats carried by pigeons, normally infects when immuno suppressed.
Primary pathogens:
Histoplasma, Blastomyces (Fungi)
[Do Not Occur in the UK]
Opportunistic invaders:
Aspergillus and Penicillium (fungi) Rare often a consequence of discospondylitis or osteomyelitis.
Extension of nasal aspergillosis through the cribriform plate has been observed.
Clinical signs are dependent on lesion location and are often multi-focal.
Pathogen spread and access to the CNS?
Entry to body -> Spread -> a.) Neurotropic (from peripheral nerves - nerve to nerve) - Intra-axonal modes of spread
OR
b.) Neural Abscess
(from a septic focus)
OR
c.) Haematogenous
(via blood)
- Bacteraemia OR viraemia
SEE IMAGE 134
How can the blood brain barrier be breached?
a. ) Transcellular
- Pathogens bind host cells and invade through the cell (i.e. binds to membrane, uptake into cell)
- Passive or active on the part of the pathogen
- Transcellular common pathogen examples:
* Bacterial= Streptococci, Listeria sp.
* Fungal= Candida (yeast), Cryptococcus (dia-morphihic fungus)
b. ) Paracellular
- Tight junctions dramatically change or new routes open
- Increased pinocytic activity leading to trans-endothlial channels formation or tight junction function can be broken
- Paracellular common pathogen examples:
* Nipah virus (Malaysia-Porcine respiratory and encephalitis syndrome).
* Lyme disease (bacterial) - Borrelia burgodorferi a spirochete.
c.) Intracellular within leucocytes (Torjan horse)
- Requires primary infection
- Pathogen inside cell (e.g. macrophage) and so not recognised by host immune system- spreads where cell goes (i.e. migrates through endothelial layers)
- May be refractive to antibody once established (if it spreads cell-to-cell)
- Intracellular transmigration pathogen examples:
Examples intracellular transmigration:
* SIV/ HIV
* Canine distemper
NOTE: In addition to these breaches, overgrowth and necrosis can cause indiscriminate damage to tissue
NOTE: Some organisms can also enter by different routes
How do viruses cause infection?
How do bacteria cause infection?
> Viruses:
- Have host-cell binding proteins that MUST bind to specific receptors on endothelia to progress
- Example: Distemper uses receptors which are on many different types of cells
> Bacteria:
- Surface proteins (Pili or outer-membrane proeteins, OMPs) increase adhesion of bacteria to cells
- The binding MAY trigger specific invasion mechanisms
- Once inside the cell, the intracellular bacteria require a survival mechanism
Pathogens can trigger inflammation: what are the consequences of this?
NOTE: Non specific inflammation can be caused by attracted leucocytes
Impacts neuronal tissue (can be indirect: pressure from attracted cells)
COMPLETE Infection indicators slide
Slide 17
What is Canine Distemper Virus (infection and spread overview)?
Describe Distemper virus? Consequences of being enveloped?
> CDV (infection/spread overview):
- Infectious disease of dogs and other carnivores
- Pantropic – generalised infection in many organ systems as the receptors are common on many cells
- Spread: close contact or by aerosols infect via URT then go systemic
> Distemper virus:
- Pleomorphic, enveloped virus
- Negative sense single stranded RNA
- Attaches to cells using F-protein
- Replication in cytoplasm buds from cells
> As it is enveloped: - Relatively labile: Sensitive to heat, desiccation, lipid solvents and non-ionic detergents and disinfectants SO isolation and disinfection can control outbreaks
- Vaccines: H-protein can be used to induce neutralising antibodies
NOTE: (GENERALLY) enveloped viruses are more labile than non-enveloped- easier to disinfect and persist less well in environment
Canine Distemper: immunity?
> Rate of spread in a patient depends on development of neutralising antibody:
- If neutralising antibody develops after 7-days: PI the virus disappears rapidly from the lymphatic tissues
- If there is no measurable antibody by day 9: the virus spreads throughout body
> Some dogs after apparent recovery can get demyelination developing leading to death (40-60 days after recovery). This is immune mediated
> Rare in responsive dogs prolonged immunity can be life long, although there is old dog encephalitis in cases
> Vaccination is a modified live vaccine. A proportion of dogs not immune after 1 year
(This is EXTRA information)
Infections through peripheral nerves:
- Listeriosis
- Rabies
Agent and susceptible?
ALSO:
- Vomiting and wasting disease
- Aujeszkys disease
> Listeriosis:
- Agent= Listeria monocytogenes
- Susceptible= Sheep, Cattle, Llamas, Goats
> Rabies:
- Agent= Lyssavirus
- Susceptible=Domestic sp. especially canine and feline
Fungi that can cause neurological infection?
> NOTE: fungal infections of CNS= fairly uncommon in dogs/cats (more common in warm, humid conditions)
> Fungi that can cause neurological infection:
Cryptococcus neoformans (dimorphic yeast) Can infect cats carried by pigeons, normally infects when immuno suppressed.
Primary pathogens:
Histoplasma, Blastomyces (Fungi)
[Do Not Occur in the UK]
Opportunistic invaders:
Aspergillus and Penicillium (fungi) Rare often a consequence of discospondylitis or osteomyelitis.
Extension of nasal aspergillosis through the cribriform plate has been observed.
Clinical signs are dependent on lesion location and are often multi-focal.
Focus of fungal infection is respiratory. With some spread to CNS. In case of nasal infection it the spread of severe disease to near-by neurological tissues.
URT: through nose and up through bone to neurological tissue e.g. the brain (top R image)
While infections may be consider lower frequency a number of toxins of algae and fungi do interact with the nervous system
Toxins of the CNS:
Ingestion and infection?
Ingestion
Toxins can be produced in feed and pasture and by microorganisms.
Infection
Toxins can be produced during infections
Toxins can be produced by colonisation of young animals by toxin producing bacteria normally excluded from the intestine.
Can ingest toxins
Infection: organism produces toxins
How does bacteraemia affect the CNS?
- CNS has intricate blood supply
- Infection in capillary spreads and causes abscesses at site of overgrowth
- Can result in non-specific neurological signs
How does viraemia affect the CNS?
- Usually in lymphatic tissue prior to development of viremia
- Viruses only infect tissues where they cells have reports for infection by that virus
How does a neural abscess affect the CNS?
- Local infection and overgrowth of bacteria
- Leads to:
physical damage of local CNS due to compression etc.
OR
spread to CNS tissue and subsequent damage
Intra-axonal modes of transport?
Retrograde and antigrade (up and down)
Listeria (overview):
- General features?
- Zoonoses?
- Main clinical manifestations?
> General features:
- Gram positive, rod, facultative anaerobes, small haemolytic colonies
- Cattle outbreaks: usually associated with silage feeding
- Humans: unpasteurised dairy products and pate
> Zoonoses:
- Source: eating contaminated food
- Can affect: pregnant women, newborns, and adults with weakened immune systems
> Main clinical manifestations:
- Sepsis
- Meningitis (often complicated by encephalitis)
NOTE: Note Listeria will spread in other cells/tissues, not just neuronal, hence a problem with pregnancy
How is Listeria spread?
- Listeria attaches to and enters mammalian cells
- This attachment induces phagocytosis
- Listeria release themselves from the vacuoles with listeriolysin
- Move in cells and between cells by nucleating actin
- Hence they can spread is neurotropic (nerve cell to nerve cell)
Listeriosis in ruminants?
Listeria found in the environment.
Outbreaks tend to be seasonal.
They can an replicate in poor quality silages pH above 5.5.
In good quality silage multiplication is inhibited by acid pH
In ruminants may present as encephalitis, abortion, septicaemia, or endophthalmitis
One source of susceptibility is decreased cell-mediated immunity associated with advanced pregnancy
Listeriosis in ruminants?
Listeria found in the environment (outbreaks tend to be seasonal)
Can replicate in poor quaity silages (pH 5.5
Listeria:
Clinical signs?
Treatment?
Prevention?
> Clinical signs (cattle from ocular infection)
- Dullness, circling and tilting of head facial paralysis
- Unilateral facial paralysis can result in drooling and dropping of eyelids and ears
> Treatment
- In early stages with antibiotics
- NOTE: Vaccines do NOT work as the pathogen is intracellular
> Prevention
- Do not feed poor quality silage (especially NOT to pregnant ruminants)
- Ensure feed method used reduces ocular contact
How is rabies spread?
- Variety of reservoirs (most common animal reservoir= bats)
- Present in infected carnivore’s saliva
- Bite proximal leg
- Virus replicates in muscles
- Virus reaches sensory/motor nerve ends
- Binds acetylcholine receptor (or other sensory end receptors)
- Virus enters distal reaches of nerves and begins second stage of infection
- Neuronal infection with centripetal passive movement within axons
(“retrograde axoplasmic flow”) - Reaches CNS (spinal cord initially)
- Virus reaches limbic system of brain and replicates extensively here (leads to the aberrant behaviour) (“furious rabies”)
- Spread continues clinical replication in cortex (“dumb rabies”)- Cell pathology low, but cells all contain virus.
- Centrifugal spread to periphery: organs, salivary glands where virus buds from cytoplasmic membrane different from nerves
SEE IMAGE 135
What is Rabies?
- RNA virus
- Rod shaped
- Enveloped
- Present in saliva transmitted by biting carnivores
- Causes encephalitis in mammals, invariably fatal
- Mammalian species vary wildly in their susceptibility
- A range of animal reservoirs (Principle reservoir in Europe= red fox, principle reservoir in North America= raccoons, skunks, foxes and bats)
- Most clinical cases due to rabies virus genotpye-1 lyssavirus
- Several species adapted strains of rabies have been described
- A number of other neurotropic Lyssaviruses closely related to rabies virus indistinguishable from rabies
Spare
Spare
Fungi that can cause neurological infection?
COMPLETE THIS
> NOTE: fungal infections of CNS= fairly uncommon in dogs/cats (more common in warm, humid conditions)
> Fungi that can cause neurological infection:
a. ) Cryptococcus neoformans (dimorphic yeast)
- Can infect cats carried by pigeons, normally infects when immuno suppressed.
Primary pathogens:
Histoplasma, Blastomyces (Fungi)
[Do Not Occur in the UK]
Opportunistic invaders:
Aspergillus and Penicillium (fungi) Rare often a consequence of discospondylitis or osteomyelitis.
Extension of nasal aspergillosis through the cribriform plate has been observed.
Clinical signs are dependent on lesion location and are often multi-focal.
Focus of fungal infection is respiratory. With some spread to CNS. In case of nasal infection it the spread of severe disease to near-by neurological tissues.
URT: through nose and up through bone to neurological tissue e.g. the brain (top R image)
While infections may be consider lower frequency a number of toxins of algae and fungi do interact with the nervous system
Toxins of the CNS:
Ingestion and infection?
Toxin producing bacteria?
Toxins produced in symbiotic on pasture?
Toxins produced by plants?
Non-microbial toxins?
> Ingestion=
Toxins can be produced in feed and pasture and by microorganisms
> Infection
- Toxins can be produced during infections
- Toxins can be produced by colonisation of young animals by toxin producing bacteria normally excluded from the intestine
> Toxin producing bacteria (infection and ingestion):
- Tetanus (Clostridium tetani)
- Botulism (Clostridium botulinum)
- Oedema disease (E. coli)
> Toxins produced in symbiotic on pasture:
- Rye grass staggers (Neotyphodium lolii fungal endophyte - New Zealand)
- This occurs sporadically in UK with imported rye grass
> Toxins produced by plants:
- Algae
> Non-microbial toxins:
- Loads (Lead, arsenic, organophosphates)
Overview of Clostridia? (The organism)
- Relatively large, Gram-positive, rods, form endospores.
- Strict anaerobes
- Vegetative cells are killed by exposure to O2
- Spores are able to survive long periods of exposure to air
SEE IMAGE 136
Clostridial neurotoxins?
Two examples of these?
- The toxins are proteins
- Act at low doses (wear gloves)
- Potentially fatal
- ) Tetanus toxin (produced by C. tetani):
- 1 antigenic type
- Synaptic inhibition
- Muscular spasms - ) Botulinum toxin (produced by C. botulinum):
- 7 antigenic types
- Inhibits neuromuscular transmission
- Flaccid paralysis
How does viraemia affect the CNS?
- Usually in lymphatic tissue prior to development of viremia
- Viruses only infect tissues where they cells have reports for infection by that virus
Clostridial neurotoxins?
Two examples of these?
- The toxins are proteins
- Act at low doses (wear gloves)
- Potentially fatal
- ) Tetanus toxin (produced by C. tetani):
- 1 antigenic type
- Synaptic inhibition
- Muscular spasms (spastic paralysis)
- C. tetani toxins produced by organisms replicating locally in tissues or wounds
- Can affect multiple animals
- Toxoinfectious
2.) Botulinum toxin (produced by C. botulinum):
- 7 antigenic types
- Inhibits neuromuscular transmission
- Flaccid paralysis
Infects one animal, unless transmitted
- Intoxication
- C. botulinum toxin produced in decaying organic matter (bodies) and problem is from ingestion
Clostridium neurotoxin: flaccid vs spastic paralysis?
Antitoxins?
- In both cases: toxins bind the somatic and enters nerve terminals
> Flaccid paralysis=
- Botulinum toxin passes into the nerve terminal and interferes with acetylcholine release (irreversible stops vesicle fusion in nerve end)
> Spastic paralysis=
- Tetanus toxin stops inhibitory transmitter binding at synapse so get continuous stimulation
> Antitoxins:
- Antitoxins are available that neutralise circulating toxin
- They are only effective before the toxin has entered the nerve terminals
- Recovery is by axonal sprouting and re-innervation. (Slow)
- A vaccine is available for horses and cattle in endemic areas
NOTE:
- Ascending tetanus is toxin spread from the site of administration along the regional nerve and the anterior roots into the spinal cord
- Descending tetanus is based upon toxin spread by way of circulation
Fungi that can cause neurological infection?
> NOTE: fungal infections of CNS= fairly uncommon in dogs/cats (more common in warm, humid conditions)
> Fungi that can cause neurological infection:
- Cryptococcus neoformans (dimorphic yeast)
Can infect cats carried by pigeons, normally infects when immuno suppressed. - Primary pathogens:
Histoplasma, Blastomyces (Fungi)
[Do Not Occur in the UK] - Opportunistic invaders:
Aspergillus and Penicillium (fungi)
Rare, often a consequence of discospondylitis or osteomyelitis - Extension of nasal aspergillosis through the cribriform plate has been observed
- Clinical signs are dependent on lesion location and are often multi-focal
Focus of fungal infection= respiratory, with some spread to CNS
In nasal infection: it is the spread of severe disease to near-by neurological tissues
URT: through nose and up through bone to neurological tissue e.g. the brain
While infections may be consider lower frequency, a number of toxins of algae and fungi do interact with the nervous system
How does the enteric nervous system fit into the CNS?
SEE IMAGE 137 (2 parts)
NOTE: Enteric nervous system can work independently (e.g. take guts out and they will still function)
Basic plan of mammalian autonomic nervous system?
SEE IMAGE 138
AND printed diagram
NOTE: Innervation by parasympathetic and sympathetic NS to GI tract
Enteric NS:
Development?
- mainly derived from cells of vagal segment of neural crest
- First cranial over
- Subsequent caudal move to populate entire GIT- Ganglia of hindgut receive an additional contribution from the sacral segment of the neural crest
Enteric NS:
General structure?
Ganglia structure?
Nerve plexus structure?
> Intramural (enteric) NS:
- Highly developed
- Largely independent enteric NS in the wall (intramural) of the gastrointestinal tract from the oesophagus to the anus and associated glands
- Consists of:
a. ) Intramural ganglia
b. ) 2 major intramural plexuses
NOTE: exists within walls of gut
> Ganglia
= tightly-packed nerve cell bodies and glial cells
- 2 main types of neurons:
* Type 1- many club-shaped proecces plus a single, long, slender process
SEE IMAGE
type 2: multiaxonal (multipolar), many long, smooth processes
SEE IMAGE
- Glial cells:
* Outnumber neurons, modulating inflammatory responses in the intestine
2 nerve plexus:
2 layers: 1 below mucosa (Meissner) and other between 2 layers of muscles (Auerbach)
Enteric NS:
General structure?
Ganglia structure?
Nerve plexus structure?
> Intramural (enteric) NS:
- Highly developed
- Largely independent enteric NS in the wall (intramural) of the gastrointestinal tract from the oesophagus to the anus and associated glands
- Consists of:
a. ) Intramural ganglia
b. ) 2 major intramural plexuses
NOTE: exists within walls of gut
> Ganglia
= tightly-packed nerve cell bodies and glial cells
- 2 main types of neurons:
* Type 1- many club-shaped proecces plus a single, long, slender process
SEE IMAGE
type 2: multiaxonal (multipolar), many long, smooth processes
SEE IMAGE
- Glial cells:
* Outnumber neurons, modulating inflammatory responses in the intestine
2 nerve plexus:
2 layers: 1 below mucosa (Meissner) and other between 2 layers of muscles (Auerbach)
Submucosal nerve plexus (Meissner plexus)
=>in lamina submucosa
Myenteric nerve plexus (Auerbach plexus)
=>between the two main muscle layers
Enteric NS:
Function?
CONTROLS: MOTILITY
> Motility:
- Tonic inhibition
- Segmental contraction
- Forward propagating contraction
- Backward propagating contraction (e.g. vomiting)
- Sphincteric function
> Motility in intestine:
- Muscle contractions in intestine wall
- Segmentation: Local contractions to mix the contents
- Peristalsis: Wave like contractions along the axis to transport the contents
> Excitatory and inhibitory fibres:
- Excitatory fibres (acetylcholine) project primarily in oral direction
-Inhibitory fibres (nitrous oxide) project primarily in aboral direction
NOTE: this arrangement is involved in the promotion of peristaltic contractions
Enteric NS:
Function?
CONTROLS: MOTILITY
> Motility:
- Tonic inhibition
- Segmental contraction
- Forward propagating contraction
- Backward propagating contraction (e.g. vomiting)
- Sphincteric function
> Motility in intestine:
- Muscle contractions in intestine wall
- Segmentation: Local contractions to mix the contents
- Peristalsis: Wave like contractions along the axis to transport the contents
> Excitatory and inhibitory fibres
(SEE SEPARATE FLASHCARD)
> Interstitial cells of Cajal
(SEE SEPARATE FLASHCARD)
> Peristalsis
(SEE SEPARATE FLASHCARD)
Autonomic innervation of intestine?
- Afferent fibres:Visceral Sensibility = Viscero-afferent fibres
Efferent fibres:Parasympathetic
-> increased motility, digestion
Sympathetic
-> reduced motility
Afferent and efferent fibres in short reflex arcs: Intramural nervous system
Parasympathetic: increase motility
Sympathetic fibres: reduce motility, reduce activity of endo/exo -crine glands in GI tract
Visceral afferent fibres (project from GI tract to the CNS)
Efferent fibres= towards GI tract, away from CNS
Interactions between CNS and ENS?
Motor input from CNS: parasympathetic and sympathetic
Sensory output to the CNS (primary afferent neurons)
Sympathetic impulses?
reduce gut motility
=>reduce glandular secretion
COMPLETE 28
Enteric NS:
a. ) General structure?
b. ) Ganglia structure?
c. ) Nerve plexus structure?
a. ) Intramural (enteric) NS:
- Highly developed
- Largely independent enteric NS in the wall (intramural) of the gastrointestinal tract from the oesophagus to the anus and associated glands
- Consists of:
a. ) Intramural ganglia
b. ) 2 major intramural plexuses
NOTE: exists within walls of gut
b.) Ganglia
= tightly-packed nerve cell bodies and glial cells
- 2 main types of neurons:
* Type 1- many club-shaped proecces plus a single, long, slender process
SEE IMAGE
type 2: multiaxonal (multipolar), many long, smooth processes
SEE IMAGE
- Glial cells:
* Outnumber neurons, modulating inflammatory responses in the intestine
c.) 2 nerve plexus:
- Submucosal nerve plexus (Meissner):
- in lamina submucosa
- best developed in small intestine
- important part in secretory control
- Myenteric nerve plexus (Auerbach):
- between the two main muscle layers
- extends the entire length of the gut
- primarily provides motor innervation to the two muscle layers and secretomotor innervation of the mucosa
ALSO: projections to gallbladder, pancreas, sympathetic ganglia
SEE IMAGE 142
Afferent impulses
-transmitted through pathways parallel to the efferent
Vagal: glucose, amino acids, long chain fatty acids,
Splanchnic: visceral nociception, vomiting reflex
What is Equine dysautonomia?
What is Canine, feline dysautonomia?
Equine dysautonomia:
Grass sickness
-polyneuropathy of the central, autonomous and enteric nervous system
-probably caused by bacterial neurotoxins (Clostridium botulinum?)
-mortality ~ 95%
-mainly in the UK
main symptom: gut paralysis
Canine, feline dysautonomia:
Ileus (a symptom)
- disruption of the normal propulsive ability of the gastrointestinal tract
Examples of clinical situations which include the GI tract
Interactions between CNS and ENS?
- Motor input from CNS (parasympathetic and sympathetic)
- Sensory output to the CNS (primary afferent neurons)
What does the enteric NS get input from?
ADD IMAGE
- CNS (via sympathetic and parasympathetic fibres)
- Local sensory cells in the gut wall
What is the enteric system influenced/innervated by?
COMPLETE THIS
- Post ganglionic sympathetic fibres
- Preganglionic parasympathetic fibres
Sympathetic impulses?
Parasympathetic impulses?
> Sympathetic impulses:
- Reduce gut motility
- Reduce glandular secretion
COMPLETE 28
> Parasympathetic impulses:
- Increase motility
- Increase secretion
- Parasympathetic fibres reach the enteric nervous system directly
Afferent impulses
Afferent impulses:
- transmitted through pathways parallel to the efferent
- Vagal: glucose, amino acids, long chain fatty acids
- Splanchnic: visceral nociception, vomiting reflex
Examples of clinical situations which include the GI tract:
What is Equine dysautonomia?
What is Canine, feline dysautonomia?
> Equine dysautonomia=
Grass sickness:
- Polyneuropathy of the central, autonomous and enteric nervous system
- Probably caused by bacterial neurotoxins (Clostridium botulinum?)
- Main symptom: gut paralysis
Canine, feline dysautonomia:
- Ileus (a symptom)
- Disruption of the normal propulsive ability of the GI tract
Enteric NS:
Development?
- Mainly derived from cells of vagal segment of neural crest
- First cranial over
- Subsequent caudal move to populate entire GIT- Ganglia of hindgut receive an additional contribution from the sacral segment of the neural crest
Enteric NS:
- ) General structure?
- ) Ganglia structure?
- ) Nerve plexus structure?
1.) General structure=
Intramural (enteric) NS:
- Highly developed
- Largely independent enteric NS in the wall (intramural) of the gastrointestinal tract from the oesophagus to the anus and associated glands
- Consists of:
a. ) Intramural ganglia
b. ) 2 major intramural plexuses
NOTE: exists within walls of gut
2.) Ganglia structure=
- Tightly-packed nerve cell bodies and glial cells
> 2 main types of neurons:
* Type 1:
Many club-shaped processes plus a single, long, slender process
SEE IMAGE 139
* Type 2:
Multiaxonal (multipolar), many long, smooth processes
SEE IMAGE 140
- Glial cells:
* Outnumber neurons, modulating inflammatory responses in the intestine
3.) Nerve plexus structure=
2 nerve plexus:
- Submucosal nerve plexus (Meissner):
- in lamina submucosa
- best developed in small intestine
- important part in secretory control
- Myenteric nerve plexus (Auerbach):
- between the two main muscle layers
- extends the entire length of the gut
- primarily provides motor innervation to the two muscle layers and secretomotor innervation of the mucosa
ALSO: projections to gallbladder, pancreas, sympathetic ganglia
SEE IMAGE 142
Examples of neurotransmitters found in the enteric nervous system and their function?
Enteric NS ‘fine-tunes’ control of the enteric NS as regulation of the digestive processes is complex- achieved by complexity of neurotransmitters and neurons
Examples of these:
Acetyl choline
Norepinephrine
Nitric oxide
Explain the interstitial cells of Cajal?
Central to GI motility regulation
- Modified smooth muscle cells
- Pacemaker for gut contraction
- Different frequencies in different parts of GI-tract
- Modulated by nervous and hormonal input
- Amplify neuronal input
NOTE: Pacemaker cells keep the neurons going but this does not necessarily result in contraction- the cells must be stimulated for this to occur
What is peristalsis?
Result of a series of local reflexes: contraction of intestinal muscle “above” intraluminal stimulus and relaxation of muscle “below”
Autonomic innervation of intestine?
> Afferent fibres:
- Visceral Sensibility
= Viscero-afferent fibres
> Efferent fibres: - Parasympathetic = increased motility and digestion - Sympathetic = reduced motility
Afferent and efferent fibres in short reflex arcs: Intramural nervous system
NOTE:
Visceral afferent fibres (project from GI tract to the CNS)
Efferent fibres= towards GI tract, away from CNS
Examples of clinical situations which include the GI tract:
What is Equine dysautonomia?
What is Canine, feline dysautonomia?
> Equine dysautonomia=
Grass sickness:
- Polyneuropathy of the central, autonomous and enteric nervous system
- Probably caused by bacterial neurotoxins (Clostridium botulinum?)
- Main symptom: gut paralysis
Canine, feline dysautonomia:
- Ileus (a symptom)
- Disruption of the normal propulsive ability of the GI tract
Examples of neurotransmitters found in the enteric nervous system and their function?
Enteric NS ‘fine-tunes’ control of the enteric NS as regulation of the digestive processes is complex- achieved by complexity of neurotransmitters and neurons
Examples of these:
Acetyl choline
Norepinephrine
Nitric oxide
Classification of neurons?
SEE IMAGE 143
What does the enteric nervous system control?
Can the enteric nervous system function independently from CNS?
> Controls:
- Motility
- Exocrine/endocrine secretions
- Microcirculation of the gastrointestinal tract
- Regulating immune and inflammatory processes
> Can function independently from the CNS
Fibres in the ENS?
> Excitatory and inhibitory fibres:
- Excitatory fibres (use acetylcholine and/or substance P) project primarily in oral direction
-Inhibitory fibres (use nitrous oxide) project primarily in aboral direction
NOTE: this arrangement is involved in the promotion of peristaltic contractions
SEE IMAGE 141
Intestinal Peristaltic Reflex?
SEE IMAGE 144
NOTE: CNS impacts on all of this and gets information from all of this
CNS gets all information (e.g. smell, taste, HR, etc)
Examples of clinical situations which include the GI tract:
What is Equine dysautonomia?
What is Canine, feline dysautonomia?
> Equine dysautonomia=
Grass sickness:
- Polyneuropathy of the central, autonomous and enteric nervous system
- Probably caused by bacterial neurotoxins (Clostridium botulinum?)
- Main symptom: gut paralysis
Canine, feline dysautonomia:
- Ileus (a symptom)
- Disruption of the normal propulsive ability of the GI tract
Innervation of GI tract?
Innervation of the gastrointestinal tract. The neural plexuses in the gut represent an independently functioning network known as the enteric nervous system, which is connected to the central autonomic neural network in the central nervous system by parasympathetic and sympathetic nerves.
Parasympathetic ganglia are located inside enteric NS
SEE IMAGE 145
What is the enteric system influenced/innervated by?
- Post ganglionic sympathetic fibres
- Preganglionic parasympathetic fibres
SEE IMAGE 146
Sympathetic impulses?
Parasympathetic impulses?
> Sympathetic impulses:
- Reduce gut motility
- Reduce glandular secretion
SEE IMAGE 147
> Parasympathetic impulses:
- Increase motility
- Increase secretion
- Parasympathetic fibres reach the enteric nervous system directly
Where do all of the cranial nerves start?
In the brain
Where do each of the cranial nerves come from?
Cranial nerve:
1 and 2= forebrain
3= midbrian
4-12= pons or medulla
Mesencephalon, Metencephalon and Myelencephalon?
Mesencephalon
Midbrain
Metencephalon
Cerevellum & Pons
Myelencephalon
Medulla oblongata
SEE IMAGE 148
What are the 12 cranial nerves?
12 cranial nerves in order rostrocaudally: I - olfactory nerve II - optic nerve III - oculomotor nerve IV - trochlear nerve V - trigeminal nerve VI - abducens nerve VII - facial nerve VIII - vestibulocochelar n. IX - glossopharyngeal n. X - vagus nerve XI - accessory nerve XII - hypoglossal nerve
What are the 12 cranial nerves?
12 cranial nerves in order rostrocaudally: I - olfactory nerve II - optic nerve III - oculomotor nerve IV - trochlear nerve V - trigeminal nerve VI - abducens nerve VII - facial nerve VIII - vestibulocochelar n. IX - glossopharyngeal n. X - vagus nerve XI - accessory nerve XII - hypoglossal nerve
SEE IMAGE 149
How to cranial nerves leave the brain?
- Must come out of the skull- through foramina
- Individually or in groups
How can the cranial nerves be grouped into 3?
> Special senses Olfactory Optic Vestibulocochlear > Innervation of head muscles Oculomotor Trochlear Abducens Hypoglossal Innervation of structures originating from branchial arches Trigeminal Facial Glossopharyngeal Vagus Accessory
How can the cranial nerves be grouped into 3?
> Special senses:
- Olfactory
- Optic
- Vestibulocochlear
> Innervation of head muscles:
- Oculomotor
- Trochlear
- Abducens
- Hypoglossal
> Innervation of structures originating from branchial arches:
- Trigeminal
- Facial
- Glossopharyngeal
- Vagus
- Accessory
How can the cranial nerves be grouped into 3?
Functional groups
> Special senses:
- Olfactory
- Optic
- Vestibulocochlear
> Innervation of head muscles:
- Oculomotor
- Trochlear
- Abducens
- Hypoglossal
> Innervation of structures originating from branchial arches:
- Trigeminal
- Facial
- Glossopharyngeal
- Vagus
- Accessory
What are structures originating from branchial arches?
Development of somites which are broken down into segments which correspond to regions of spinal cord. These somites go on to form musculature structures so each somite is innervated by specific nerve.
In the head: Muscles either originate from somites or from different embryological structure
From branchial arches: Origin of skeletal musculature structures around the head
Explain olfaction (and gustation?
Gustation= taste
Chemical senses
Chemical substances stimulate special sensory cells, generate AP, impulse transported via sensory afferent fibres to the brain (these fibres run in cranial nerves)
Olfaction: Well-developed in dogs (macrosmatic) Important for orientation in environment Olfactory mucous membrane in the nasal fundus = olfactory region Olfactiory region= - Perforated ehtymoidal bone at front of skull, turbinate structures in front of this - Back portion of nasal cavity - Within this= olfactory epithelium
Olfactory epithelium: see separate flashcard
Describe olfactory epithelium?
NOTE: Olfactory neurosensory cells are supported by supporting cells and basal cells
> Olfactory neurosensory cells - Bulb of dendrite - Dendrite - Axon (olfactory fibre) > Supporting cells > Basal cells
SEE IMAGE
Describe olfactory epithelium?
Describe olfactory cells?
OLFACTORY EPITHELIUM=
> NOTE: Olfactory neurosensory cells are supported by supporting cells and basal cells: > Olfactory neurosensory cells - Bulb of dendrite - Dendrite - Axon (olfactory fibre) > Supporting cells > Basal cells SEE IMAGE 150
OLFACTORY CELLS=
- Nerve cells which are replaced continuously by division of basal cells
- Primary sensory cells
SEE IMAGE 151
What are structures originating from branchial arches?
Development of somites which are broken down into segments which correspond to regions of spinal cord. These somites go on to form musculature structures so each somite is innervated by specific nerve.
In the head: Muscles either originate from somites or from different embryological structure
From branchial arches: Origin of skeletal musculature structures around the head
Explain olfaction (and gustation)?
Gustation= taste
Chemical senses
Chemical substances stimulate special sensory cells, generate AP, impulse transported via sensory afferent fibres to the brain (these fibres run in cranial nerves)
Olfaction: Well-developed in dogs (macrosmatic) Important for orientation in environment Olfactory mucous membrane in the nasal fundus = olfactory region Olfactiory region= - Perforated ehtymoidal bone at front of skull, turbinate structures in front of this - Back portion of nasal cavity - Within this= olfactory epithelium
Olfactory epithelium: see separate flashcard
What are TSEs?
Transmissable Spongiform Encephalopathy (defined by their effect on nervous tissue):
- Nuerodegenerative disease (Chronic progressive infection of NS)
- Caused by prions (Proteinaceous infectious particle, singl proteins with sugar decorations (glycoproteins))
- Long incubation period (years)
SEE IMAGE 152
What causes TSEs?
(‘Unconventional’ disease agents)
Prions=
- Stanley Prusiner’s ‘prion theory’: Derived from native glycoprotein (protein with sugar decorations)
- Resistant to: treatments that selectively destroy DNA/RNA
- Sensitive to: protein-denaturing chemicals
What are prions resistant/sensitive to?
> RESISTANT TO treatments that selectively destroy DNA/RNA:
- Heat 135ºC, 18 min
- UV light
- Ionizing radiation
- DNAse, RNAse
- Zinc catalysed hydrolysis
- Most disinfectants
- Most tissue fixatives
- Some may persist after standard healthcare facility autoclaving conditions (e.g. 121°C for 15 minutes)
- SENSITIVE TO protein-denaturing chemicals:
- Urea
- SDS (chemical)
- Phenol etc
What are TSEs?
Transmissable Spongiform Encephalopathy (defined by their effect on nervous tissue):
- Nuerodegenerative disease (chronic progressive infection of NS)
- Caused by prions (Proteinaceous infectious particle, single proteins with sugar decorations (glycoproteins))
- TSEs such as BSE= zoonotic
- Long incubation period (years)
- Fatal
- TSE agent resistant to disinfection (normal autoclave procedure)
- Incurable to date, no vaccine available
- Vast economical impact
SEE IMAGE 152
What causes TSEs?
(‘Unconventional’ disease agents)
Prions=
- Stanley Prusiner’s ‘prion theory’: Derived from native glycoprotein (protein with sugar decorations)
- Resistant to: treatments that selectively destroy DNA/RNA
- Sensitive to: protein-denaturing chemicals
PrP^c = normal cellular prion protein PrP^Sc = abnormal scrapie prion protein (PrP^BSE)
Rat + inject TSE infected material= clinical signs, death
Rat + inject PrP^c-/- = no clinical signs
-> PrP^c = required for TSEs development
BUT PrP^c = not essential (function so far unknown)
What are prions resistant/sensitive to?
> RESISTANT TO treatments that selectively destroy DNA/RNA:
- Heat 135ºC, 18 min
- UV light
- Ionizing radiation
- DNAse, RNAse
- Zinc catalysed hydrolysis
- Most disinfectants
- Most tissue fixatives
- Some may persist after standard healthcare facility autoclaving conditions (e.g. 121°C for 15 minutes)
- SENSITIVE TO protein-denaturing chemicals:
- Urea
- SDS (chemical)
- Phenol etc
Difference between PrP^c and PrP^Sc?
PrP^c = normal cellular prion protein
- Rich in alpha helices
PrP^Sc = abnormal scrapie prion protein (PrP^BSE)
- Rich in beta sheets
= Different conformation, different sensitivity to proteases
SEE IMAGE 153
NOTE: Tendency to aggregate and now resistant to proteases
What is prion species barrier?
- Not all prion disease easily infect other species- limited by ‘species barrier’
- Depends on differences in the primary structure of prion proteins in the infecting inoculum and the host
- Once species barrier overcome: incubation time decreases, transmissibility increase
- Prion strains
How do animals get infected with PrP^Sc?
ingestion of PrPSc contaminated feeds Meat-and-bone meal prepared from slaughter offal – protein dietary supplement to cattle
- horizontal transmission during perinatal period placental material from scrapie infected ewes may play important role
Milk (scrapie) does not appear to occur in cattle - superficial abrasions
- Environment (saliva, faeces, urine etc)
Stays in environment for a long time
How does PrP^Sc get to the brain?
We don’t know very much
very long incubation time, no acute stage – research difficult
- Information mainly from scrapie in sheep or TSE in mice
Diagram
Proposed routes of transport to CNS?
parasympathetic fibres of vagus nerve
Bypasses spinal cord
Innervates the viscera of head, neck, thorax, abdomen, incl. ileum
Originates in medulla oblongata
(2) Splanchnic nerves/
sympathetic trunk
enteric plexus pre-vertebral ganglia splanchnic nerves sympathetic trunk spinal cord brain
(3) Sympathetic & vagosympathetic trunk sympathetic trunk cervicothoracic ganglion ansa subclavia vagosympathetic trunk brain
What causes TSEs?
(‘Unconventional’ disease agents)
Prions=
- Stanley Prusiner’s ‘prion theory’: Derived from native glycoprotein (protein with sugar decorations)
- Resistant to: treatments that selectively destroy DNA/RNA
- Sensitive to: protein-denaturing chemicals
PrP^c = normal cellular prion protein PrP^Sc = abnormal scrapie prion protein (PrP^BSE)
Rat + inject TSE infected material= clinical signs, death
Rat + inject PrP^c-/- = no clinical signs
-> PrP^C = required for TSEs development
BUT PrP^c = not essential (function so far unknown)
Difference between PrP^c and PrP^Sc?
PrP^C = normal cellular prion protein
- Rich in alpha helices
PrP^Sc = abnormal scrapie prion protein (PrP^BSE)
- Rich in beta sheets
= Different conformation, different sensitivity to proteases
SEE IMAGE 153
NOTE: Tendency to aggregate and now resistant to proteases
What is prion species barrier?
- Not all prion diseases easily infect other species- limited by ‘species barrier’
- Depends on differences in the primary structure of prion proteins in the infecting inoculum and the host
- Once species barrier overcome: incubation time decreases, transmissibility increase
- Prion strains
How do animals get infected with PrP^Sc?
- ) Ingestion of PrP^Sc contaminated feeds
- Meat-and-bone meal prepared from slaughter offal (protein supplement for cattle)
2.) Horizontal transmission during perinatal period (time immediately before/after birth) - Placental material from scrapie infected ewes
- Milk (scrapie)
NOTE: does not appear to occur in cattle
3.) Superficial abrasions?
- ) Environment (bodily fluids etc.)?
- Stays in environment for a long time
How does PrP^Sc get to the brain?
COMPLETE slide 15
- Long incubation time- difficult to research
- Information mainly from scrapie in sheep or TSE in mice
Diagram
Proposed routes of transport to CNS?
1.) Parasympathetic fibres of vagus nerve:
- Bypasses spinal cord
- Innervates the viscera of head, neck, thorax, abdomen, incl. ileum
2.) Splanchnic nerves/ sympathetic trunk:
Enteric plexus -> pre-vertebral ganglia -> splanchnic nerves -> sympathetic trunk -> spinal cord -> brain (Infection spreads very slowly)
3.) Sympathetic and vagosympathetic trunk:
Sympathetic trunk -> cervicothoracic ganglion-> ansa subclavia -> vagosympathetic trunk -> brain
Primary site of pathogenic prions?
= Obex
Caudal part of medulla oblongata (between medulla oblongata and spinal cord)
Is it possible to vaccinate against TSEs:
a. ) PrP^C
b. ) PrP^Sc?
a.) Vaccination against PrP^C:
- Recombinant mouse prion (produced by bacteria) used as a vaccine= delays but does not prevent onset of prion disease in normal mice- optimisation possible
RISK: vaccine itself might cause an autoimmune disease in some people
b. ) Vaccination against PrP^Sc:
- No immune response associated with infection with PrPSc (no protective antibody production)
TSEs:
Diagnosis- live animal?
Changes in behaviour
locomotion
hypersensitivity to touch, sound, visual stimulation
Mild signs may go unnoticed
Signs may be seen in other disease (eg rabies, BVD)
20% of the cattle diagnosed positive by clinical signs turn out to be negative after post mortem examination i.e. are false positives.
Definitive diagnosis only by post mortem testing
costs of screening (cattle, sheep, goat)
TSEs:
Diagnosis- post mortem?
Tests for clinically affected cattle or sheep (Defra)
Histopathology
- post-mortem - brain material preserved in formalin, stained and examined under the microscope for the characteristic appearance of BSE specific changes.
- limitations: - any degree of decomposition before the brain is examined - spongiform appearance is not exclusive to TSEs
A diagnosis of TSE can only be made by demonstrating the presence of prion protein
(1) Transfer of brain extract to permissive experimental animal (susceptible mouse strain Ethical issues long incubation period before diagnosis costs
(2) Specific identification of the PrPSc, the disease specific protein
Interaction of specific antibodies with a disease specific protein PrPSc.
PrPSc is more resistant to degradation by proteases (proteinase K) and can be differentiated from PrPC on this basis.
Limitations does not work on formalin fixed brain samples
(1) Rapid screening test
Protease treatment required prior to tests
PrPC is degraded
PrPSc is partially purified and detected by ELISA using specific antibodies
TSEs:
Post mortem sampling for TSE testing?
Key target sites for diagnosis in TSE:
- nucleus of the solitary tract (A)
nucleus of the spinal tract of the trigeminal nerve (BSE) (B)
- dorsal motor nucleus of the vagus nerve. (scrapie) (C)
TSEs in animals?
BSE
Scrapie
Chronic Wasting Disease (CWD)
Transmissible mink encephalopathy
Feline spongiform encephalopathy
BSE:
Clinical signs?
NOTE: Clinical signs are NOT sufficient to diagnose BSE
Changes in Behaviourincl
Apprehension, nervousness or aggression
Repeated, exaggerated reactions to touch, sound, visual stim.
excessive nose licking
Changes in Posture and Movement
Weakness or high stepping in the legs, particular the hind legs
difficulty in rising, progressing to recumbency (downer cow)
Later Signs
Reduced milk yield
Weight Loss
Death
Cerebella aplasia/hypoplasia (bovine viral diarrhoea/mucosal disease)
Other neurological diseases that show similar clinical signs to BSE include:
● Metabolic, endocrine disorders
(Hypomagnesaemia
Hypocalcaemia
Nervous ketosis)
● Infectious disease(Listeriosis, Rabies)
● Toxic syndromes
(Lead poisoning) ● Rare inherited diseases
What is atypical scrapie?
- Apparently healthy animals, presented with ataxia without evidence of pruritus or wool loss
- Rapid screening ELISAs: positive
- Western blot: low molecular weight fragment
- Immunopathology in rostral areas of the brain incl. cerebellum
- Immunostaining at obex confined to spinal tract nucleus of trigeminal nerve not dorsal motor nucleus of the vagus nerve
- Older animals
What is Chronic Wasting Disease (CWD)?
- Only prion disease known to affect free-ranging wild life
- Free-ragning mule deer, white-tailed deer, Rocky mountain elk
CWD:
Clinical signs?
Changes in Behaviour
incl
Separation from other animals in the herd
Depression or blank facial expression
Changes in Posture and Movement incl Unsteady and poor co-ordination of movement Weakness Paralysis
Later Signs
Weight loss
Death
What are prions resistant/sensitive to?
CHECK autoclaving methods which are effective/not effective?
> RESISTANT TO treatments that selectively destroy DNA/RNA:
- Heat 135ºC, 18 min
- UV light
- Ionizing radiation
- DNAse, RNAse
- Zinc catalysed hydrolysis
- Most disinfectants
- Most tissue fixatives
- Some may persist after standard healthcare facility autoclaving conditions (e.g. 121°C for 15 minutes)
- SENSITIVE TO protein-denaturing chemicals:
- Urea
- SDS (chemical)
- Phenol etc
- High concentrations of sodium hypochlorite
- heated strong solutions of sodium hydroxide
Difference between PrP^c and PrP^Sc?
PrP^C = normal cellular prion protein
- Rich in alpha helices
PrP^Sc = abnormal scrapie prion protein (PrP^BSE)
- Rich in beta sheets
PrPSc is more resistant to degradation by proteases (proteinase K)
= Different conformation, different sensitivity to proteases
SEE IMAGE 153
NOTE: Tendency to aggregate and now resistant to proteases
Proposed mechanism of PrP^Sc accumulation?
COMPLETE SLIDE 12
SEE IMAGE 157
TSEs:
Post mortem sampling for TSE testing?
Key target sites for diagnosis in TSE:
1.) Nucleus of the solitary tract
2.) BSE: Nucleus of the spinal tract of the trigeminal nerve (BSE)
3.) SCRAPIE: Dorsal motor nucleus of the vagus nerve
SEE IMAGE 154
TSEs:
Diagnosis- post mortem?
> Histopathology
a.) post-mortem
a.) BSE: brain material preserved in formalin, stained and examined under microscope
BUT:
- possible decomposition before brain is examined - spongiform appearance is not exclusive to TSEs
TSE only diagnosed if prion presence can be proved:
a.) transfer brain extract to permissive experimental animal
(susceptible mouse strain)
BUT:
- ethical issues
- long incubation period before diagnosis
- costs
b. ) Specific identification of the PrP^Sc (the disease-specific protein)
d. ) PrPSc is more resistant to degradation by proteases (proteinase K) SO differentiated from PrP^C on this basis
i.) Rapid screening test= Protease treatment required prior to tests
PrP^C= degraded
PrP^Sc= partially purified and detected by ELISA using specific antibodies
BUT
- does not work on formalin fixed brain samples
ii.) Western blotting=
Protease treatment required prior to tests
Detects PrP^Sc protein by molecular weight and reaction with specific antibodies
(NOTE: don’t see anything on negative sample)
BUT
- time-consuming
- labour-intensive
- ELISA= much quicker
SEE IMAGE 155
> Immunohistochemistry:
- use specific antibodies
- tes directly on tissue section (no protein purification steps)
> Electron microscopy of Scrapie Associated Fibrils - Can use decomposed samples BUT - expensive - time-consuming - labour- intensive SEE IMAGE 156
How does PrP^Sc get to the brain?
COMPLETE slide 15
- Long incubation time- difficult to research
- Information mainly from scrapie in sheep or TSE in mice
SEE IMAGE 158
BSE:
Current screening process?
Positive rapid test ->
Immunohistochemistry
OR
EM (SAFs) (decomposed samples)
Link between vCJD and BSE?
Epidemiological studies have suggested a link between the 2
- Same geographical areas for both
- Strain-typing studies show they were caused by same strain of agent
- Interspecies transmission of BSE possible
- Bioassays of tissues from cattle with BSE show they are infectious
= Huge economic impact on UK economy
How do SAF effect an animal>
Accumulation of insoluble Scrapie associated fibrils (SAF) in nerve cells
= High concentration of PrPSc ->
Spongiform encephalopathy of the cerebellar cortex ->
Locomotion disturbance & ataxia
Susceptibility to Scrapie?
Goats: All susceptible
Sheep: Depends on genotype (determined from blood sample)
- PrP has 2 alleles (one from each parent)
- 5 different scrapie related alleles in sheep:
ARR
AHQ
ARH
ARQ
VRQ
- Homozygous genotype= same alleles from both parents (e.g. ARR/ARR or AHQ/AHQ)
- Heterozygous genotype= different allele from each parent (e.g. ARR/ARH or ARQ/VRQ)
SO: 15 genotypes
- ARR= not susceptible
- VRQ= are susceptible
Compulsory Scrapie Flocks scheme?
SLIDE 39
Actions taken to reduce Scrapie prevalence?
> Suspect cases of Scrapie:
- Report to AHDO
- VO farm visit
- Slaughter and tests
- Movement restrictions
> Compulsory Scrapie Flocks Scheme (CSFS)
- Flocks with suspected case are automatically registered
- State Veterinary Service VO visit to identify all sheep/goats on holding:
i. ) Cull and destroy carcasses: restock with resistant breeding sheep
ii. ) Genotyping: Retain sheep with resistant genotypes and others culled for food chain if appropriate
Scrapie:
Current screening process?
Positive rapid test ->
Immunochemistry
OR
Electronmicroscopy (SAFs) (decomposed samples)
BOTH ->
PrP genotyping codons 136, 154, 171
CWD:
Clinical signs?
Changes in Behaviour
incl
Separation from other animals in the herd
Depression or blank facial expression
Changes in Posture and Movement incl Unsteady and poor co-ordination of movement Weakness Paralysis
Later Signs
Weight loss
Death
BSE:
Clinical signs?
NOTE: Clinical signs are NOT sufficient to diagnose BSE
> Changes in behaviour:
- Apprehension
- Aggression
- Hypersensitivity to touch, sound, visual stim.
- Excessive nose licking
- Reluctance to turn corners, go through doorways etc.
> Changes in posture and movement:
- Weakness or high stepping in the legs (particularly hind legs)
- Difficulty in rising, progressing to recumbency (downer cow)
> Later Signs:
- Weight Loss
- Reduced milk yield
- Death
> Cerebella aplasia/hypoplasia (bovine viral diarrhoea/mucosal disease)
CWD:
Clinical signs?
> Changes in behaviour:
- Isolation from herd
- Depression or blank facial expression
> Changes in posture and movement:
- Unsteady and poor co-ordination of movement
- Hocks together
- Lowered head
- Weakness
- Paralysis
> Later Signs
- Weight loss
- Death
NOTE: Some animals may not show clinical signs except for acute pneumonia
TSEs:
How can public health risk be reduced?
- TSEs are spread by puncture contact, invasive techniques (e.g. surgery) or ingestion
- They can spread by infecting nerve cell ends and lymph cells
- Estimated survival time in soil: 3 years (+)
Time in the environment: 16+ years? - Autoclaving 134ºC, 18 min, (close to max temp) lab waste incinerated after autoclaving
- High concentrations of sodium hypochlorite or heated strong solutions of sodium hydroxide are reported to be effective
Scrapie:
Animals affected?
Clinical signs?
> Sheep, goats
> Clinical signs:
a. ) Pruritus (irritation)
- Repeated scratching/rubbing against posts etc.
- Leads to excessive wool loss or damage to skin
- Positive scratch response (nibbling/ licking when scratched on back)
b. ) Changes in behaviour
- Increased nervousness
- Excitable
- Agression
- Depression
c. ) Changes in posture/movement (e.g. ataxia)
- Severe incoordination
- Stumbling
- Standing awkwardly
- Weak hind legs
d. ) Later signs:
- Weight loss
- Death
CWD:
Clinical signs?
> Changes in behaviour:
- Isolation from herd
- Depression or blank facial expression
- Increase thirst and urination
- Difficulty swallowing
- Excess salivation
- Pneumonia
> Changes in posture and movement:
- Unsteady and poor co-ordination of movement
- Hocks together
- Lowered head
- Weakness
- Paralysis
> Later Signs
- Weight loss
- Death
NOTE: Some animals may not show clinical signs except for acute pneumonia
Compulsory Scrapie Flocks scheme?
SEE IMAGE 159
What is Chronic Wasting Disease (CWD)?
- Only prion disease known to affect free-ranging wild life
- Free-ragning mule deer, white-tailed deer, Rocky mountain elk
Feline Spongiform Encephalopathy clinical signs?
> Changes in behaviour:
- timidity
- aggression
- hyperaesthesia (sensitivity gen)
- head tremor
- muscle fasciculations (trembling)
- jaw-champing
- drooling/excessive salivation
> Changes in posture and movement:
- staggering or crouching gate
- ataxia
Feline Spongiform Encephalopathy clinical signs?
> Changes in behaviour:
- timidity
- aggression
- hyperaesthesia (sensitivity gen)
- head tremor
- muscle fasciculations (trembling)
- jaw-champing
- drooling/excessive salivation
> Changes in posture and movement:
- staggering or crouching gate
- ataxia
Cerebellum: Location? Major division? Ventricle? Subdivision?
> Location: - In caudal part of cranial cavity - Caudal to the tentorium cerebelli - Dorsal to the 4th ventricle SEE IMAGE 160
> Divisions:
Hindbrain, fourth ventricle, metencephalon
NOTE:
Cerebellum is 1 of the main subdivisions of the brain (cerebrum, cerebellum, brainstem)
Development of the cerebellum?
1.)
Hindbrain: Medulla oblongata, pons, cerebellum
- )
- Paired upgrowth from future pons part of hindbrain
- Fuse into single cerebellum
- Lies dorsal to pons, medulla oblongata and 4th ventricle
- Remains attached to brainstem by 3 paired peduncles (NOT part of brainstem)
How is the cerebllum attached to the brainstem?
NOTE: attached to it but NOT a part of it
```
> 3 pairs of Peduncles:
- Rostral
to midbrain
- Middle
(to pons)
- Caudal
(to medulla obongata)
~~~
Cerebellum:
Adult structure=
> Gross parts?
> Gross parts:
- Vermis
- Hemispheres (2)
- Middle part= vermis, hemispheres seen either side of this
NOTE: Divide does not exist from anatomic point of view
> Lobes:
- Rostral
- Caudal
- Flocculonodular
NOTE: Lobes have a functional relationship
Cerebellum:
Evolutionary divisions?
Archicerebellum: flocculonodular lobe
Paleocerebellum: rostral lobe
Neocerebellum: caudal lobe – largest in highest mammals along with large cerebral hemispheres
Cerebellum: Location? Major division? Ventricle? Subdivision?
> Location: - In caudal part of cranial cavity - Caudal to the tentorium cerebelli (tentorium cereblli seaparates cerebrum and cerebellum) - Dorsal to the 4th ventricle SEE IMAGE 160
> Divisions:
Hindbrain, fourth ventricle, metencephalon
NOTE:
- Cerebellum is 1 of the main subdivisions of the brain (cerebrum, cerebellum, brainstem)
- Has high density of neurones
Development of the cerebellum?
1.)
Hindbrain: Medulla oblongata, pons, cerebellum
2.)
- Paired upgrowth from future pons part of hindbrain
- Fuse into single cerebellum as they meet in the middle, continued growth in dorsal direction
SEE IMAGE 161
- Lies dorsal to pons, medulla oblongata and 4th ventricle (can not see 4th ventricle without removeing cerebellum)
- Remains attached to brainstem by 3 paired peduncles (NOT part of brainstem)
How is the cerebellum attached to the brainstem?
What do these allow?
> Peduncles attach the cerebellum to the brainstem
NOTE: attached to it but NOT a part of it
> Peduncles allow fibres to enter/leave cerebellum
> 3 pairs of Peduncles:
- ) Rostral:
- Attach to midbrain
- Efferent: majority, via thalamus to cerebral cortex
- Afferent: ventral spinocerebellar tract, tectocerebellar
2.) Middle:
- Attach to pons
- Afferent: all, from pons, Corticopontocerebellar
pathway ( =pathway from motor centre in cortex to cerebellum via pons)
- Efferent: NONE
- Well-developed in species with highly-developed motor skills (involved in complex motor function)
- ) Caudal:
- Attach to med. obl.
- Afferent: Present, dorsal spinocerebellar, reticulocerebellar, olivocerebellar, cuneocerebellar, vestibulocerebellar
- Efferent: Present, cerebellovestibular, cerebelloreticular
SEE IMAGE 162 (2 parts)
Summary:
Rostral: Mainly efferent fibres, some afferent fibres
Middle: ONLY afferent fibres
Caudal: afferent AND efferent fibres
Cerebellar development:
Initial zones?
- ) Mantle zone
- Cellular
- Deep
- Gives rise to cerebellar cortex - ) Marginal zone
- Firbous
- Superficial
- Gives rise to white matter
SEE IMAGE 163
LATER:
- Some mantle zone= migrates to surface to become cerebellar cortex
- Remainder= stays deep to form cerebellar nuclei
Cerebellar development:
Initial zones?
- ) Mantle zone
- Cellular
- Deep
- Gives rise to cerebellar cortex - ) Marginal zone
- Firbous
- Superficial
- Gives rise to white matter
SEE IMAGE 163
LATER:
- Some mantle zone= migrates to surface to become cerebellar cortex
- Remainder= stays deep to form cerebellar nuclei
Cerebellar cortex: histology?
1 Pia mater 2 Granular cell layer 3 White matter 4 Molecular layer SEE IMAGE 165
1 Molecular layer 2 Purkinje cell layer 3 Granular cell layer 4 Purkinje cells SEE IMAGE 166
Cerebellar cortex:
Overall structure?
SEE IMAGE 167
- Climbing fibres reaching far into molecular layer
- Mossy fibres synapse first in granule cells layer
- Granule cells into molecular layer
- Afferent fibres travelling into cerebellar
- Output is not directly from cerebellar cortex AS it is relayed via cerebellar nuclei (purkinje cells provide output but synapsed by cerebellar nuclei)
SEE IMAGE 167
Cerebellum:
Adult structure=
> Gross parts?
> Gross parts:
- Vermis
- Hemispheres (2)
- Middle part= vermis, hemispheres seen either side of this
NOTE: Divide does not exist from anatomic point of view (cerebellum seen as 1 structure)
> Lobes:
- Rostral
- Caudal
- Flocculonodular
NOTE: Lobes have a functional relationship
Cerebellum:
Adult structure=
> Gross parts?
> Gross parts: - Vermis - Hemispheres (2) - Middle part= vermis, hemispheres seen either side of this SEE IMAGE 168
NOTE: Divide does not exist from anatomic point of view (cerebellum seen as 1 structure)
> Lobes: - Rostral - Caudal - Flocculonodular SEE IMAGE 169
NOTE: Lobes have a functional relationship
Cerebellum:
Evolutionary divisions?
> Archicerebellum:
- Flocculonodular lobe
- Oldest part of cerebellum
- First in fish
- FUNCTION= Vestibular system: balance, equilibrium
- Purkinje fibres projecting directly to brainstem
> Paleocerebellum:
- Rostral lobe
- First in amphibians
- FUNCTION= major spinocerbebellar afferent tracts terminate here, coordinates truncal and limb movements
> Neocerebellum:
- Caudal lobe
- Largest in highest mammals along with large cerebral hemispheres
- FUNCTION= Input via pons, controls skilled movement
- Input is via middle peduncle
SEE IMAGE 170
Explain cerebellar hypoplasia?
- Diseases associated with cerebellar malfunction
- Very small cerebellum
- Lack of coordination or posture
- Loss of motor function etc.
SEE IMAGE 171
Further notes on embryology
Changes in cell shape and number lead to folding. The neural plate invaginates along its axis to form a neural groove, with neural folds on each side. The neural folds move together and fuse dorsally, turning the fold into the neural tube. The neural tube gives rise to the tissues of the central nervous system – the brain rostrally and the spinal cord caudally. Neuroepithelial cells are bipotential and can form neurons or supporting neuroglial cells.
Some neuroectodermal cells from the lateral edges of the neural plate are not incorporated into the neural tube but persist as ‘neural crest’ cells, dorsal to the neural tube. Neural crest cells separate into left and right columns and have tremendous potential for migration. They give rise to the cells of various ganglia, of the cranial and spinal nerves, and form a wide variety of other structures.
Closure of the neural tube progresses antero-posteriorly. Once the neural tube has closed completely, meninges and vertebral structures develop around it.
Cerebellar afferent fibres?
1.) Proprioceptive input (ipsilateral) from the limbs, body and head:
spinocerebellar, vestibulocerebellar, tectocerebellar pathways
2.) Input about planned motor activity:
a.) Coordination of function (learned, complex, voluntary)from motor cortex (contralateral) originates from cerebrum (via internal capsule), thalamus, midbrain (crus cerebri) and nuclei in pons to middle cerebellar peduncle (corticopontocerebellar pathway)
(Return pathway: Rostral cerebral peduncle)
b) Input relevant to coordination of the extrapyramidal function (semiautomatic movement, posture, locomotion), ), originates from cerebrum, thalamus, midbrain and projecting to the olivary nucleus in the medulla oblongata (via caudal peduncle)
NOTE: Cerebellar needs to know about current motor function before any further motor activity occurs (e.g. to reach something from the desk, you must be aware, first, that you are sitting down)
Explain intracerebellar communication:
Incoming fibres?
Output from cerebellar cortex?
> 2 types of incoming (afferent) fibres entering cerebellum:
- ) Mossy fibres
- Excite granule cells which project to molecular layer and excite Purkinje cells
- Single mossy fibre can excite several granule cells
- Mossy fibres excite stellate cells which inhibit Purkinje cells - ) Climbing fibres
- Excite Purkinje cells (1-to-1)
- Source: Mainly olivary nuclei
BOTH FIBRES EXCITE CEREBELLAR NUCLEI
> Output from cerebellar cortex:
- Cerebellar cortex projects to cerebellar nuclei via Purkinje cell axons:
a.) Hemispheres to lateral nucleus
b.) Paravermis to interposital nucleus
c.) Vermis to fastigial nucleus
SEE IMAGE 172
Exception: Output from archicerebellum (flocculonodular lobe) inhibits vestibular nuclei of the brainstem directly
Cerebellar efferents?
1.) Lateral nucleus to the red nucleus, the reticular formation, the pallidum, and the ventrolateral nucleus of the thalamus
(from here to primary motor cortex)
- ROSTRAL PEDUNCLE
- ) Interposital nucleus to red nucleus and reticular formation
- ROSTRAL PEDUNCLE - ) Fastigial nucleus to vestibular nuclei and reticular formation
- CAUDAL PEDUNCLE
Exception: Output from archicerebellum (flocculonodular lobe) inhibits vestibular nuclei of the brainstem directly
NOTE: Cerebellum does not make contact with any lower motor neurones (those innervating muscles)
SO cerebellum does not induce movement
Cerebellar efferents?
1.) Lateral nucleus to the red nucleus, the reticular formation, the pallidum, and the ventrolateral nucleus of the thalamus
(from here to primary motor cortex)
- ROSTRAL PEDUNCLE
- ) Interposital nucleus to red nucleus and reticular formation
- ROSTRAL PEDUNCLE - ) Fastigial nucleus to vestibular nuclei and reticular formation
- CAUDAL PEDUNCLE
Exception: Output from archicerebellum (flocculonodular lobe) inhibits vestibular nuclei of the brainstem directly
NOTE: Cerebellum does not make contact with any lower motor neurones (those innervating muscles)
SO cerebellum does not induce movement
General function of the cerebellum?
- Controls timing and pattern of muscle activation during movement
- Maintenance of equilibrium (in conjunction with vestibular system)
- Regulates muscle tone: modulates spinal cord/brain stem mechanisms involved in postural control
= Coordinates motor function for posture and movement BUT can not initiate movement
General function of the cerebellum?
- Coordinates movment: Controls timing and pattern of muscle activation during movemen (in agonsit/antagonist muscles)
- Maintenance of equilibrium (in conjunction with vestibular system)
- Regulates muscle tone: modulates spinal cord/brain stem mechanisms involved in postural control (sets appropriate tone in postural muscles on which movement is superimposed)
- It compares input from motor planning centers with subconscious proprioceptive input
= Coordinates motor function for posture and movement BUT can not initiate movement
Dysfunctions of cerebellar?
> Cerebellar lesions can result in either or both of:
- Inadequate processing of incoming proprioceptive information= subconscious proprioceptive deficits
- Inadequate output for modulating motor activity=
motor activity is usually excessive
When does the cerebellum develop in different species?
- Prey species: Cerebellum almost entirely developed in animals that are able to get up and walk straight after birth
- Altricial aniamals (humans/kittens etc.): are unable to do this as their cerebellum undergoes much slower development and isn’t fully developed at this stage
Types of cerebellar dysfunctions?
Vestibocerebellar signs?
Spinocerebellar signs?
Pontocerebellar signs
General symptoms caused by cerebellar dysfunctions?
Types of cerebellar dysfunctions:
> Cerebellar lesions can result in either or both of:
- Inadequate processing of incoming proprioceptive information= subconscious proprioceptive deficits
- Inadequate output for modulating motor activity=
motor activity is usually excessive
Vestibocerebellar signs:
disturbance of equilibrium, swaying posture and wide-based stance
Spinocerebellar signs:
Hypermetria and hypertonus (spasticity), result in exaggeration of spinal reflexes (hopping, wheelbarrowing, hemiwalking)
Pontocerebellar signs:
Loss of harmony and synchrony in movements (dysmetria, overshooting, tremor)
(dysfunction in voluntary movements)
NOTE: Dysmetria consists of hypometria/hypermetria:
Hypometria=
voluntary muscular movements tend to result in the movement of bodily parts short of the intended goal
Hypermetria=
voluntary muscular movements tend to result in the movement of bodily parts beyond the intended goal
> General symptoms caused by cerebellar dysfunction:
- Ataxia= altered direction and extent of voluntary movements. Abnormal gait and uncoordinated movements
- Dysmetria= altered range of motion (usually hypermetria and hypertonus)
- ‘Intention tremor’= oscillating motion (especially head) during movement
- Vestibular signs= nystagmus, head tilt
- NOTW: not paralysis/muscle weakness (it is lack of coordination)
When does the cerebellum develop in different species?
- Prey species: Cerebellum almost entirely developed in animals that are able to get up and walk straight after birth
- Altricial animals (humans/kittens etc.): are unable to do this as their cerebellum undergoes much slower development and isn’t fully developed at this stage
Eye variations between species, human/dog/cat/horse/sheep/ snake/avian/fish:
Cilia?
Shape of pupil?
> Human
- Upper/lower cilia
- Round pupil
> Dog
- Upper cilia
- Round pupil
> Cat
- No lashes (modified guard hairs)
- Vertical slit pupil
> Horse
- Upper cilia, prominent virbrissae
- Horizontal, oval pupil
> Sheep
- Upper cilia
- Horizontal oval pupil
Eye variations between species, human/dog/cat/horse/sheep/ snake/avian:
Cilia?
Shape of pupil?
> Human
- Upper/lower cilia
- Round pupil
> Dog
- Upper cilia
- Round pupil
> Cat
- No lashes (modified guard hairs)
- Vertical slit pupil
> Horse
- Upper cilia, prominent virbrissae
- Horizontal, oval pupil
> Sheep
- Upper cilia
- Horizontal oval pupil
> Snake
- Fused eyelids
- Vertical slit pupil/variable
> Avian (owl)
- Modified feathers instead of cilia
NOTE: horizontal oval pupil allow prey species to see predators
What is heterochromia iridum?
Different iris colour in each eye
What is a fundus?
What is a fundic (tapetal reflex in animals) reflex?
Fundus=
back of eye when viewed with ophthalmoscope
Fundic/tapetal reflex= shine/reflection from fundus (or tapetum). Colour of reflection= colour of fundus
NOTE: this is not a reflex, it is a reflection
What is fundus colour related to?
Pigment: coat colour, iris, fundus
Embryology of the eyes?
- Develos from forebrain (depressions in forebain, where eyes will be, = optic sulci)
- Develops from 3 tissue types:
1. ) Neuroectoderm
2. ) Surface ectoderm
3. ) Mesoderm
Embryology of the eyes?
- Develos from forebrain (depressions in forebain, where eyes will be, = optic sulci)
- Develops from 3 tissue types:
1.) Neuroectoderm
2.) Surface ectoderm
3.) Mesoderm
SEE IMAGE 173
SEE IMAGE 174 (3 parts)
What is optic neuritis?
Inflammation of the optic nerves
Example of it in vivio:(looks blurred/fuzzy)
SEE IMAGE 175
Link between systemic disease and eyes?
Systemic diseases often present in the eyes
Embryology of the eyes?
- Develop from forebrain (depressions in forebain, where eyes will be, = optic sulci)
- Develops from 3 tissue types:
1.) Neuroectoderm
2.) Surface ectoderm
3.) Mesoderm
SEE IMAGE 173
SEE IMAGE 174 (3 parts)
What are the ocular layers (tunics)?
- ) OUTER layer
- Fibrous
- Protection
- Rigidity
* Sclera
* Cornea - ) MIDDLE layer
- Vascular
- Nutrition
* Uveal tract: choroid, ciliary body, iris - ) Inner layer
- Neural
- Allows vision
* Retina
* Optic nerve
SEE IMAGE 178
NOTE: Sclera turns transparent and become cornea at front of eye
What are the ocular layers (tunics)?
- ) OUTER layer
- Fibrous
- Protection
- Rigidity
* Sclera
* Cornea - ) MIDDLE layer
- Vascular
- Nutrition
* Uveal tract: choroid, ciliary body, iris - ) Inner layer
- Neural
- Allows vision
* Retina
* Optic nerve
SEE IMAGE 178
SEE IMAGE 179
NOTE: Sclera turns transparent and become cornea at front of eye
What are the ocular layers (tunics)?
- ) OUTER layer
- Fibrous
- Protection
- Rigidity
* SCLERA
* Cornea - ) MIDDLE layer
- Vascular
- Nutrition
* Uveal tract: CHOROID, ciliary body, iris - ) Inner layer
- Neural
- Allows vision
* RETINA
* Optic nerve
SEE IMAGE 178
SEE IMAGE 179
SEE IMAGE 242
NOTE: Sclera turns transparent and become cornea at front of eye
Eye:
Anterior segment?
Posterior segment?
Anterior segment=
Everything up to and including lens
Posterior segment=
Posterior to lens
Parts of the anterior segment of the eye (canine)?
- Medial/Lateral canthus (corners of eye where eyelids meet) - Conjunctiva (covers sclera) - Limbus (junction between cornea/sclera) - Lower/upper eyelid (cilia only on upper in dogs) - Third eyelid/nictitating membrane (medial corner of eye) - Iris (coloured part) - Pupil (central) SEE IMAGE 183
Parts of the nasolacrimal drainage system (tear drainage system)?
- Upper punctum
(tear duct opening) - Canaliculus
- Lacrimal sac
- Nasolacrimal duct
(tear duct) - To nose, ipsilateral nostril
(Upper/lower cannaliculi join at enlarged section (lacrimal sac which then flows into nasolacrmial duct)
Parts of the nasolacrimal drainage system (tear drainage system)?
- Upper punctum (tear duct opening) - Canaliculus (eye to lacrimal sac) - Lacrimal sac (join canniculi) - Nasolacrimal duct (lacrimal sac to nostril)
Upper/lower cannaliculi join at lacrimal sac (enlarged section) to form nasolacrmial duct which flows into ipsilateral nostril
SEE IMAGE 184
Parts of the posterior segment of the eye (view of fundus)?
- Sclera (around the circumference) - Choroid (lining inside the sclera) - Retina (clear substance, lining inside of globe) - Tapetal fundus (dorsal, reflective area) - Non-tapetal fundus (ventral, non-reflective area) - Optic nerve head/disc
SEE IMAGE 184
Function of the eye?
> VISION
- Collect light from environent and focus it onto photoreceptors in retina
- Phototransduction (convert light to nerve impulse)
How can you measure pressure of the orbit?
- Foot plate rests on cornea
- Sliding metal plunger indents cornea to varying degrees
- Measures degree of indentation which is converted to an IOP
- High number on scale= Low IOP= soft eye = more indentation
- Low number on scale= High IOP= hard eye= less indentation
- Hold ‘holder’ between thumb and finger
- Instrument should be vertical with curved footplate horizontal as it rests on cornea
- Read where needle points on measuring scale
- Use table to convert reading to IOP
SEE IMAGE 181 - Different weights can be placed on instrument to allow cross-reference of values
- The default weight is 5.5g but you can add 7g, 10g and 15g weights
- For example, using the default 5.5g weight, a reading of 5 from the measuring scale will represent an IOP of 17.3
- If you add the 7.5g weight, a reading of 5 from the measuring scale will represent an IOP of 25.8
SEE IMAGE 182
Optics:
Where does refraction occur in the eye?
(Bending of light rays as they travel between different mediums)
> CORNEA:
- Air-cornea interface
(most of the focusing in the eye occurs here)
> Lens
- Aqueous-lens interface
- Len-vitreous interface
SEE IMAGE 186
Ocular histology?
SEE IMAGE 187-195
What is the orbit and what is its purpose?
= Cavity within skull, encloses eye
- Bony cone with soft tissue floor
- Foramina within walls of orbit allow vasculature/innervation to eye
- Two types of orbit:
- Open or incomplete
- Closed or complete
Purpose:
- Protection
- Separated eye from cranial cavity
Compare the two types of orbit?
- ) OPEN (incomplete)
- Lateral wall is soft tissue
- Facilitates wide opening of jaw (catch prey)
- Carnivores (dog, cat) and pig - ) Closed (complete)
- Lateral wall is bone
- Protection for fighting (e.g. mating rituals)
- Herbivores (horse, cow, sheep, goat)
SEE IMAGE 196
How does skull shape influence orbit shape (e.g. between breeds)?
> Pug:
- Shallow orbit
> Labrador
> Rough collie
- Deep set eyes
How does canine skull shape influence orbit shape (e.g. between breeds)?
Feline orbit shape?
> Pug:
- Shallow orbit
> Labrador
> Rough collie
- Deep set eyes
> Feline
- Deep orbits
- Protection
Anatomy of the orbit:
Bones?
Walls?
Medial wall Very thin, underlying ethmoturbinates Floor Part bone, part soft tissue Masticatory muscles (masseter and ptyerygoid muscles) Rostral margin/orbital rim Lateral wall Closed or complete orbits Fusion of zygomatic and frontal bones
Open or incomplete orbits
Lateral orbital ligament
Palpate as taut band in live animal
Facilitates access for biopsy, ultrasound, surgery
Rostral rim: includes frontal, lacrimal and zygomatic bones
Where are the teeth comparative to the orbit?
Relevance of this:
* Complications?
* Benefits?
Access to orbit via oral cavity
Compare the two types of orbit?
- ) OPEN (incomplete)
- Lateral wall is soft tissue (lateral orbital ligament)
- Facilitates wide opening of jaw (catch prey)
- Carnivores (dog, cat) and pig - ) Closed (complete)
- Lateral wall is bone (fusion of zygomatic and frontal bones)
- Protection for fighting (e.g. mating rituals)
- Herbivores (horse, cow, sheep, goat)
SEE IMAGE 196
How does canine skull shape influence orbit shape (e.g. between breeds)?
Feline orbit shape?
> Brachycephalic skull
- Shallow orbit
- Eyes look prominent
- Little protection for eye
- Pug
> Mesaticephalic skull
- Labrador
> Dolichocephalic skull
- Deep set eyes
- Eyes look smaller (less exposed)
- More protection for eyes
- Rough collie
SEE IMAGE 198
> Feline
- Deep orbits
- Protection
- More force needed for eye to prolapse
Anatomy of the orbit:
Bones?
Walls?
- 5-7 bones (species-dependent)
- Soft tissue structures
Medial wall Very thin, underlying ethmoturbinates Floor Part bone, part soft tissue Masticatory muscles (masseter and ptyerygoid muscles) Rostral margin/orbital rim Lateral wall Closed or complete orbits Fusion of zygomatic and frontal bones
Open or incomplete orbits
Lateral orbital ligament
Palpate as taut band in live animal
Facilitates access for biopsy, ultrasound, surgery
Rostral rim: includes frontal, lacrimal and zygomatic bones
Anatomy of the orbit:
Bones?
Walls?
> Bones - 5-7 bones (species-dependent) - Feline orbit: * Maxillary bone * Frontal bone * Lacrimal bone * Ethmoidal bone * Palatine bone * Sphenoid bone * Zygomatic bone SEE IMAGE 197
> Walls:
- Medial wall=
- Very thin
- Underlying ethmoturbinates
- Floor=
- Partly bone/soft tissue
- Masticatory muscles (masseter and ptyerygoid muscles)
- Rostral margin/orbital rim=
- Frontal, lacrimal and zygomatic bones
SEE IMAGE 199 - Lateral wall=
- Closed/Complete OR Open/Incomplete
Soft tissue orbit: extraconal and associated structures?
> Masticatory muscles
- Temporalis m.
- Pterygoid m.
- Masseter m.
> Glands
- Lacrimal gland (dorsolateral)
- Zygomatic salivary gland (ventral)
- NOTE: Problems with salivary glands (glandular issues) may present as eye problems
> Blood vessels/nerves
> Fat and connective tissue
> Nasal cavity
> Oral cavity and teeth roots
> Paranasal sinuses
> Cranial cavity (cranial fossa)
SEE IMAGE 200
Where are the teeth comparative to the orbit?
Relevance of this:
* Complications?
* Benefits?
- Upper teeth roots= very close to orbit
- Rabbits:
Tear duct infection presents as chronic ocular discharge;
often related to dental problem - Tools to extract teeth may slip through soft tissue floor of orbit and into eye
- Access to orbit via oral cavity (e.g. for a biopsy)
Canine paranasal sinuses?
Equine paranasal sinuses?
Canine: - Maxillary gland (just medial to orbit) - Frontal gland (just rostral to orbit) SEE IMAGE 198
Equine: - Conchofrontal sinus- frontal and drsal conchal (rostral/dorsal to orbit) - Caudal maxillary sinus (rostral/ventral to orbit) - Rostral maxillary sinus (rostral to caudal max.) SEE IMAGE 201
Relevance of zygomatic gland to the orbit?
- Major salivary gland
- Sits just below eye
- Inflammation of gland can push up into eye
What impact does jaw movement have on the globe?
Clinical relevance? Examination?
> Open jaw: vertical ramus tilts forwards and presses on back of eye: tumour or similar behind the eye means that pain is caused when jaw is opened and presses against it
> Orbital disease may cause pain during:
- Eating
- Yawning
- Examination of oral cavity (e.g. opening the patient’s mouth)
> Orbital examination:
- View from front AND from above
- Retropulsion
- Oral exam (ask about appetite e.g. soft/hard food)
- General physical exam including regional lymph nodes
Retropulsion?
- Gently press globe backwards
- Equal
- Non-painful
- Limited in brachycephalic breeds and cats (shallow orbit)
Optic foramina?
= pathway for nerves/blood vessels to reach orbit from cranial cavity
- 8 different foramina
> Optic foramen= - Optic nerve - Internal opthalmic artery > Orbital foramen= - Oculomotor nerve - Trochlear nerve - Ophthalmic nerve - Abducens nerve > Round foramen= - Trigeminal 2 > Stylomastoid foramen= - Facial nerve
Eye/orbit vasculature:
- Arterial supply?
- Venous drainage?
1.) Arterial supply
- Main supply for eye: external opthalmic artery (branch of external carotid artery)
- Supply for optic nerve and retina:
internal ophthalmic artery (branch of internal carotid artery)
- Internal ophthalmic artery enters eye with optic nerve and then branches into retinal arteries
2. ) Venous drainage
> 2 routes from orbit into orbital plexus:
- Dorsomedial region of eye
- Ventrolateral region of eye
> 2 routes from orbital plexus:
- Intracranial route=
- Orbital vein via orbital fissure
- Into cavernous sinus on base of skull
- Extracranial route=
- Internal maxillary vein
- External jugular vein via facial veins
Orbital CONE:
Soft tissue?
> Consists of periorbita and endorbita (connective tissue) wrapping around:
- Extraocular muscles (striated)
- Smooth muscle
- Nerves
- Blood vessels
- Fat
Explain the extraocular muscles?
- 7 extraocular muscles
- Attach to sclera
- Separated by fat and facial sheaths
- Form a cone wrapping around optic nerve, cone directed towards optic foramen
SEE IMAGE 203
SEE IMAGE 204 - See flashcard for innervation of extraocular muscles
SEE 2 flaschards
- ) Abnormal eye position terminology?
- ) Abnormal eye size terminology?
> How to differentiate between abnormal position or size?
3.) Abnormal pupil size terminology?
1.) Abnormal eye position
- Exophthalmos=
pushed out
(* Increased size of palpebral fissure
* Normal corneal diameter)
- Enophthalmos=
sunken in
2.) Abnormal eye size
- Microphthalmos=
small
(* Decreased size of palpebral fissure
* Smaller corneal diameter)
- Buphthalmos=
enlarged
OR
- Hydrophthalmos=
enlarged with water
> Differentiation
- Compare eyes (including aerial view)
- Size of palpebral fissure (eyelid opening)
- Position of third eyelid
- Sclera visible?
- Corneal diameter
- Appearance of eye itself
- Abnormal position=
- Eye itself looks normal
- All structures are pushed forwards/ backwards: 3rd eyelid is more prominent
- Abnormal eye size=
- Eye itself looks abnormal
- Reduced corneal diameter
SUMMARY:
Altered eye POSITION= eye looks normal
Altered eye SIZE= eye looks abnormal
NOTE: hydrophthalamus and buphthalamus= enlarged globe. Terms generally inter-changeable
3.) Abnormal pupil size
- Miosis= small pupil
- Mydriasis= dilated pupil
- Aniscocoria= difference in pupil size
Neuro-ophthalmology:
- Nerves involved?
- Nerves not involved?
- Nerves with minor roles?
> Involved:
2, 3, 4, 5, 6, 7, 8
Not involved:
1, 11, 12
Minor role:
- 9 (taste and salivary glands, related to ‘dry eye’ treatment)
- 10 (SNS fibres travel with vagus nerve, forming vago-sympathetic trunk within thorax)
Neuro-ophthalmology tests: Optic nerve (CN 2)?
> Tests of vision:
- Owner’s perception
- Observe in unfamiliar surroundings/obstacle course (patch eyes)
- Blind dogs go upstairs but NOT downstairs
> Neuro-ophthalmic tests:
- Menace response
- Tracking reflex
- Visual placing reflex
- Obstacle course
Explain the pathway for vision (visual pathway)?
- Retinal ganglion cells form optic nerve
- Optic nerve from each eye cross at chiasm and then form optic tract
- Optic tracts ends in brain lateral geniculate nucleus (relay center in the thalamus for the visual pathway) and then in visual cortex
- Ganglion cells in lateral retina stay on same side and don’t cross over
- Ganglion cells from medial retina do cross over
= optic fields overlap
SEE IMAGE 208
Neuro-ophthalmology tests: Optic nerve (CN 2)?
> Tests of vision:
- Owner’s perception
- Observe in unfamiliar surroundings/obstacle course (patch eyes)
- Blind dogs go upstairs but NOT downstairs
Nerves influencing globe and adnexa?
SEE SHEET OF PAPER FOR THIS
Neuro-ophthalmology tests: Explain the menace response: Afferent? Efferent? Areas of the brain involved? Stimulus? Normal response? Problems?
NOTE: response, not reflex- it is a LEARNED RESPONSE
> Afferent path: II
Efferent path: VII
> Involves: Conscious visual pathways Contralateral visual cortex Contralateral motor cortex Ipselateral cerebellar hemisphere
> Stimulus:
Quick, gesture towards each eye in turn
> Normal response:
Facial nerve causes stimulated eye to blink
> Problems:
- Incorrectly performed: * Contralateral eye not covered
- Air currents
- Animal gets ‘bored’
- Learned response (remember age cut-off)
Explain the tracking reflex: Afferent? Efferent? Stimulus? Normal response? Problems?
> Afferent path: II
Efferent path: III, IV, VI, VIII- globe movements
> Stimulus:
Ability to follow object (cotton wool- no smell/sound)
> Normal response:
Follow object when dropped
> Problems:
Unreliable
Explain the visual placing reflex:
Stimulus?
Normal response?
> Stimulus:
Support thorax, bring forelegs towards table top
> Normal response:
Place both forepaws on table before carpi touch surface
Explain pupillary light reflex (PLR): Afferent? Efferent? Stimulus? Normal response? Problems? PLR pathway?
> Afferent path: II
Efferent path: PNS fibres in III to pupillary constrictor muscle
> Stimulus:
light shone in one eye
> Normal response: pupil constricts - Direct PLR= Pupil on same side as light constricts - Indirect/consensual PLR= Contralateral pupil constricts
> Problems:
- False negative=
- Light source not strong enough to elicit PLR
- Animal scared/stressed (High level of SNS tone)
- Age-related atrophy of iris musculature
- Positive PLR is not necessarily consistent with vision
> PLR pathway:
Common pathway with vision fibres initially
and then PLR fibres branch off BEFORE lateral geniculate nucleus (LGN)
SEE IMAGE 205
Compare pathways or vision and PLR?
> VISION pathway:
- 1 cross over of fibres at optic chiasm, fibres then go into lateral geniculate nucleus and then to visual cortex
Right: optic pathway is grey
> BOTH: begin with retina and optic nerve and optic chiasm.
> PLR fibres branch off from visual pathway before visual cortex and go to pretectal nucleus
- Fibres then cross over again and go to PS nucleus of oculomotor nerve
- From here, post ganglionic PS fibres go to iris and make pupil constrict
SO: PS fibres carried in oculomotor nerve synapse in ciliary ganglia (near the back of the eye)
SEE IMAGE 208
Compare PLR and menace pathway?
PLR= reflex
Menace response= complex pathway
Explain dazzle reflex: Afferent? Efferent? Stimulus? Normal response? Problems? Why is it used?
PRIMITIVE, SUBCORTICAL REFLEX (assesses ability to detect light, not necessarily vision)
> Afferent pathway: retina, II, rostral colliculus, subcortical connections
Efferent pathway: VII
> Stimulus: very bright focal light shone into one eye
> Normal response:
- Both eyes blink, possible head withdrawal
- Dazzle reflex can cause animal to blink under GA
> Purpose:
- Can this eye detect light at all (prognosis)?
- Easy to demonstrate difference between normal and abnormal eye to owners
NOTE: +ve dazzle and –ve menace suggest cerebrocortical lesion
Dazzle reflex vs menace response?
> Menace response:
- Involves II and VII
- Cortical (involved visual cortex)
> Dazzle reflex:
- Involves II and VII
- Subcortical (occurs under GA, positive dazzle reflex does not mean eye has vision)
NOTE: +ve dazzle and –ve menace suggest cerebrocortical lesion
Sensory innervation of eye and eyelid?
> Trigeminal nerve: Ophthalmic and maxillary
V1= Opthalmic:
Cornea, medial canthus, nasal mucosa
V2= Maxillary:
Lateral canthus, rest of face
(V3= Mandibular:
Mandibular, lower lip)
What are the standard neuro-ophthalmic tests for vision?
Menace response
Tracking reflex
Visual placing reflex
Obstacle course
NOTE:
Perform neuro-ophthalmic test(s) in apparently NORMAL eye first- Establishes ‘baseline normal’ for that animal
Explain the corneal reflex test? Afferent? Efferent? Stimulus? Normal response? Problems?
> Afferent pathway: Vophth branch
> Efferent pathway: VI and VII
> Stimulus:
Touch cornea gently with wisp of cotton, outside of line of vision
> Normal response: Globe retracted (VI) and blink (VII)
Explain palpebral reflex? Afferent? Efferent? Stimulus? Normal response?
= BLINKING
> Afferent pathway:
V ophth and V max branches
> Efferent pathway:
VII
> Stimulus:
gently touch the medial and lateral canthi
> Normal response: blink (VII)
NOTE:
Can be used at same time as menace response
NOTE:
Test palpebral reflex first (blinking is the positive result for menace response/dazzle reflex so need to know that animal CAN blink i.e. facial nerve is functioning- SO prevents false negatives in these tests)
- For example:
Negative menace response:
* Is eye really blind?
= True negative menace response
* Is eye visual but there is ipsilateral facial nerve paralysis (cannot blink)?
= False negative menace response
Function of cranial nerve 7?
Facial nerve:CN VII
Motor innervation to muscles of facial expression
Efferent pathway for blinking
Orbicularis oculi muscle
(PNS to lacrimal gland)
Tear production
Which muscle is involved in blinking and which nerve innervates this?
- Facial nerve: efferent pathway for blinking
- Innervates orbicularis oculi muscle (involved in blinking)
How is eye movement coordinated?
How is eye movement assessed?
- 7 extraocular muscles, innervated by III, IV, VI, control eye movement
- VIII controls eye position in relation to head position AND co-ordinates III, IV, VI by medial longitudinal fasciculus (MLF)
> Assessment of eye movement:
- General observation from a distance (move in unison, asymmetry of gaze direction at rest)
- Tracking reflex
- Vestibulo-ocular reflex (VOR)
Explain the Vestibulo-ocular reflex (VOR):
Stimulus?
Normal response?
VOR in farm animals?
= ‘Dolls head reflex’ or physiological nystagmus
> Stimulus:
- Change in head position
- Side/side OR up/down
> Normal response:
- Both eyes move together:
- Fast phase in direction of head movement (to see what’s coming)
- Slow phase opposite to direction of head movement (to focus on what they were previously looking at)
> NOTE:
Helpful to observe from above and pull upper eyelids caudally to expose sclera and therefore you can see globe movement
> VOR in farm animas:
- Farm animals’ eyes move in opposite direction to head
- Cattle rolls eye downwards when examined SO move head down to make eye turn upwards
NOTE:
VOR is INDEPENDENT of vision
What is strabismus?
What is nystagmus?
> Strabismus=
- Abnormal globe position, squint
a.) Resting stabismus: present at rest
b.) Positional strabismus:
in response to moving head position, loss of vestibular control over normal eye position
- Most common type: down and out pupil, oculomotor nerve affected
- Look at blood vessel direction in retina to determine if eye is rotated
- Normal for brachycephalic breeds to have divergent strabismus
> Nystagmus=
- Involuntary rapid eye movement
a. ) Pendular nystagmus: - Opsclonus
- Continuous oscillations (no fast/slow phase)
- Not associated with vestibular problem
- Congenital visual deficits
b. ) Jerk nystagmus: - Slow and fast phases
- Vestibular disease
- Spontaneous or positional
- Strabismus and nystagmus are often associated with ocular albinism
Explain the 3 neurone pathway of sympathetic innervation?
> FIRST order neurones:
- Travel down spinal cord in tectotegmental spinal tract
- Synapse in lateral horn of spinal cord grey matter
SECOND order neurones:
- Exit via T1 to T3 nerve roots as ramus communicans (Thoracic limb innervation by brachial plexus C6-T1)
- Form thoracic sympathetic trunk
- Passes beside Vagus n, forming vagosympathetic trunk within carotid sheath
THIRD order neurones
- Pass rostrally
- Synapse in cranial cervical ganglion, beside tympanic bulla
- Pass into cranial cavity with CN V, then exit to orbit to supply eye
SUMMARY:
> FIRST order:
conduct impulses from skin receptors and proprioceptors (periphery) to brainstem/spinal cord THEN
Synapse with second order neurons in brainstem
SECOND order:
Brainstem to thalamus
THIRD order:
Thalamus to primary sensory cortex
Sympathetic nervous system innervation of the eye?
What happens if there is a SNS lesion?
NORMAL SYMPATHETIC SUPPLY > Pupillary dilator m = dilates pupil > Orbital smooth m = tone keeps globe in normal position > Eyelid smooth m = lifts upper eyelid
SNS LESION
> Pupillary dilator m
- can not dilate SO miosis (small pupil)
> Orbital smooth m
- eye sinks within orbit (enophthalmos) SO third eyelid protrusion
> eyelid smooth m
- upper eyelid droops (ptosis) SO small palpebral fissure
(i.e. Everything gets smaller)
What is Horner’s syndrome caused by?
What are the symptoms of this disease- small animal?
What are the symptoms of this disease- large animal?
- Sympathetic nervous system lesion
- Long pathway that can involve:
- Brain
- Neck
- Thorax
- Ear
- Orbit
Small animal symptoms: - Miosis - Enophthalmos - Third eyelid protrusion - Ptosis - Small palpebral fissure (i.e. Everything gets smaller) SEE IMAGE 206
Large animal symptoms:
- Less dramatic than in small animals, ptosis= most obvious clinical sign
- Horse: ipsilateral facial sweating, regional hyperthermia (head, cranial neck)- vasodilation
- Cow/sheep/goat: regional hyperthermia, vascular engorgement of pinna AND ipsilateral dry nose
Function of orbicularis oculi muscle?
- Innervated by: facial nerve
- Encircles eye and causes eyelids to close when it is stimulated by the facial nerve
SEE IMAGE 207
Neuro-ophthalmology
ALL SLIDES ARE COMPLETED
c
Why is learning important and when does it occur?
Learning is not required in constant environment and can be risky under changing conditions (time) - mostly occurs when environment changes between generations, but if conditions remain stable within generation
- can rely on genetics and pass these onto next generation
Learning and memory:
Stages?
Acquisition: registers input into buffer for analysis.
Encoding: processing of incoming information to be stored.
Consolidation: create stronger representation (short-term to long- term).
Storage: result of acquisition and consolidation to create a permanent record.
Retrieval: use of stored information (create representation or perform learned behavior).
Sensory information ->
Short-term memory -> Long-term memory
STM to LTM= consolidation
LTM to STM=
rehearsal
Non-associative learning?
Associative learning?
> Non-associative learning: Habituation, sensitisation
> Associative learning: Classical conditioning, operant conditioning
Learning and memory:
Stages?
> Acquisition=
registers input into buffer for analysis
Encoding=
processing of incoming information to be stored.
Consolidation=
create stronger representation (short-term to long-term
Storage=
result of acquisition and consolidation to create a permanent record
Retrieval=
use of stored information (create representation or perform learned behaviour)
Sensory information ->
Short-term memory -> Long-term memory
STM to LTM= consolidation
LTM to STM=
rehearsal
NOTE: not all items in STM go to LTM
Non-associative learning?
Non-associative learning can either be habituation or sensitisation
> Habituation= Reduction in response to an event
- Stimulus-specific
- Not due to exhaustion (e.g. if you changed the modality, a full response would still be generated)
Sensitisation=
- Increased responsiveness to an event
How is learning classified?
- Non-associative learning (habituation, sensitisation)
- Associative learning (classical conditioning, operant conditioning)
NOTE:
Associative learning is when you learn something new about a new kind of stimulus (that is, an extra stimulus). Non-associative learning is when you’re not pairing a stimulus with a behaviour
Explain habituation?
- Stimulus/situation has no ‘meaning’- not followed by behaviourally relevant consequence
EXAMPLE:
- Put 2 rats into a field
- Rats travel less on the second day
= Repeated exposure caused habituation to the area
What is associative learning?
Learning to make a particular response to a particular stimulus
Includes: classical and operant (instrumental) conditioning
Associative learning:
Explain classical conditioning?
- Stimulus initially produces no response
- This stimulus is followed several times by unconditioned stimulus that produces a response
- Pair an unconditioned stimulus to a conditioned stimulus produces a conditioned response
- Stimulus must be very clear to animal
- Pavlov:
Pair conditioned stimulus (metronome) with food which produces unconditioned response (salivation). Eventually: conditioned stimulus (metronome) produces conditioned response (salivation) which is the same as the unconditioned response (salivation) - Contiguity: stimuli must be paired together- eat food + get sick a few hours later= (wrongly) associate the food with the sickness, despite the two being separated by time
- Can monitor the acquisition of the response (learning) and the extinction (decrease of a response to paired stimuli if this pairing is not maintained)
Classical conditioning:
What is extinction?
- Decline of conditioned response when conditioned stimulus repeatedly occurs without presence of unconditioned stimulus it had been paired with
- NOT forgetting (can reintroduce stimuli- hasn’t forgotten response, just stopped showing it)
Associative learning: Explain operant (instrumental) conditioning?
- Behaviour is followed by consequence, nature of consequence modifies tendency to repeat the behaviour in the future
= effects of particular behaviour increase (reinforce) or decrease (punish) probability of behaviour
> Types of operant conditioning reinforcement schedules: 1.) Continuous= 1 push= 1 reinforcer 2.) Fixed ratio= x pushes= 1 reinforcer 3.) Fixed interval= 10 mins= 1 reinforcer 4.) Variable schedule= x pushes= x reinforcer
> Example
a. ) Reinforcement event that increases future probability of response:
- Rat roams around box and randomly chooses path in Y-shaped box
- Gets food reward
- Increased probability of same response (choose same path)
b. ) Reinforcement event that decreases future probability of response:
- Rat roams around box and chooses path in Y-shaped box
- Punishment: shock
- Shift to different response (choose other path)
Operant conditioning:
Explain reinforcement and punishment?
1.) REINFORCEMENT: (always increases likelihood of behaviour) a.) Positive reinforcement= Add favourable stimulus b.) Negative reinforcement= Remove undesirable stimulus
2.) PUNISHMENT: (always decrease likelihood of behaviour) a.) Positive punishment= Add adverse stimulus b.) Negative punishment= Remove desirable stimulus
Operant conditioning:
Extinction?
- Behaviour (response) that had previously been reinforced is no longer effective
> Example: Skinner’s box:
- Rat pushed=s lever to get reward but stops being rewarded and so stops pushing lever
Difference between classical and operant conditioning?
Classical conditioning involves response that is not under control of organism (Stimulus-stimulus learning)
Operant conditioning involves voluntary, controllable response (Stimulus-response learning)
NOTE: Both often described as SR learning
What other learning processes should you be aware of (other than classical/operant conditioning)?
- ) Imprinting
- Lorenz’s geese
- Phase-sensitive learning
- Occurs in sensitive period during development
- Narrowing of range of stimuli that elicit particular response
- LINK: period of socialisation in dog (week 4-14) - ) Social Learning
- Learning from another member of social group
- Learning about other members of social group to learn about group functioning:
* Improve skills e.g. hunting
* Reduces risks e.g. avoids injury - ) Latent learning
- Learning about characteristics of situation WITHOUT any reinforcer
- i.e. nothing is desirable/harmful but they form memories to learn from
- Not immediately seen in observable changes BUT may be useful a later time
What are memory consolidation phases?
- Short term memory (seconds to hours) - Long term memory (hours to months) - Long-lasting memory (months to lifetime) SEE IMAGE 209
- Must feel an emotion to consolidate a memory (helps learning to occur without the need for repetition)
- Long term memory is still susceptible to change
What is a conditioned emotional response?
A classically conditioned response that occurs
when a neutral stimulus is followed by an aversive stimulus
- Dog goes to vet and has bad experience
- Sight of car next time (conditioned stimulus) may then remind dog of traumatic experience
Conditioning of anxiety – conditioning of context?
Just need to know general concept of this
Conditioning to a tone [conditioned stimulus (CS)] involves projections from the auditory system to the lateral nucleus of the amygdala (LA) and from LA to the central nucleus of the amygdala (CE). In contrast, conditioning to the apparatus and other contextual cues present when the CS and unconditioned stimulus are paired involves the representation of the context by the hippocampus and the communication between the hippocampus and the basal (B) and accessory basal (B) nuclei of the amygdala, which in turn project to CE.
As for tone conditioning, CE controls the expression of the responses.
Stimulus travels to amygdala and makes contact with central amygdala, which causes fear reaction
Hippocampus provides contextual information
SEE IMAGE 210
The nature of learning:
What is the Hebb rule?
Cellular basis of learning involves strengthening of a synapse that is repeatedly active when postsynaptic neuron fires
i.e. neurones that are firing together are wiring together
Explain learning in relation to synaptic plasticity?
1.) Long-term potentiation=
- long-lasting enhancement in communication between neurones that results from stimulating their afferents with high frequency
(LTP)
- High rate of stimulation= produces excitatory post-synaptic potential= depolarises membrane= potentials summate= reach threshold to establish LTP
SEE IMAGE 211
- Occurs when: synapses are active (stimulate axon that forms synapse with neurone) while the postsynaptic membrane is depolarised
SEE IMAGE 212
> Learning and memory:
*Stimulus comes in and causes unconditioned (normal) response
*Conditioned stimulus comes in at same time and weak synaptic tone doesn’t mean anything BUT if it is paired enough then synapse becomes stronger and causes the same response
*Both neurones must be active and postsynaptic neurone needs to be depolarised
> Role of NMDA receptors for LTP:
- NMDA receptor= glutamate (excitatory neurotransmitter) receptor, controls calcium ion channel
- Calcium ion channel usually blocked by magnesium:
* Posysynaptic depolarisation= ejects Mg and frees channel
AND
* Presynaptic glutamate binding postsynaptically to NMDA receptors of dendritic spine
= Ca ions can enter cell
- Ca activates protein kinase (CaM-KII)
- Protein kinase causes insertion of postsynaptic AMPA receptors
- AMPA receptors control sodium channel and produce EPSPs when channel is open
2.) Long-term depresssion=
- weakening of neuronal synpapse which lasts hours/days that results from persistent low frequency synaptic stimulation
(LTD)
- Neurones stimulated with low frequency= may get excitatory postsynaptic potential BUT if very low= contributes to LTD
SEE IMAGE 211
> Oppositng forces- how synaptic plasticity evolves
Learning and memory 1 AND 2
ALL SLIDES ARE COMPLETED
COMPLETED
What are seizures?
Difference between epileptic and non-epileptic seizures?
Seizures= temporary abnormal electro-physiological phenomena of the brain, resulting in abnormal synchronization of electrical neuronal activity
- Excitation outweighs inhibition
- A seizure often has three distinct phases: aura, ictus, and postictal state
> ‘Seizure’ does not imply that the event is epileptic:
- Postictal phase only occurs in epileptic seizure
How can epileptic seizures be classified?
> Focal/partial epileptic seizure
(doesn’t affect whole brain- start in localised brain area)
- Presents with focal motor/autonomic/behavioural signs alone or in combination
> Generalised epileptic seizure
(does affect whole brain- involves cerebral hemispheres from the start)
- Presents as immediate convulsions and loss of consciousness (salivation/defecation/urination often occur during convulsions)
- Focal epileptic seizure may become generalised epileptic seizure: focal seizure with secondary generalisation
What is encephalitis?
Inflammation/infection of the brain
What is paroxysmal depolarising shift (PDS)?
c
What are convulsions?
What are they caused by?
= sudden (often violent) motor activity of cerebral or brainstem origin
- Not all epileptic seizures cause convulsions
- Caused by anything which can lead to an ion imbalance e.g.:
- Alcohol withdrawal
- Tumour
- Trauma
What is epilepsy?
- A GROUP of neurological disorders all of which develop periodic (epileptic) seizures
- Characterised by recurrent episodes of paroxysmal (sudden recurrence or intensification of symptoms) brain dysfunction due to a sudden excessive neuronal discharge
- At least two unprovoked epileptic seizures >24h apart
Do dogs circle towards/away from the side of the brain lesion causing the circling?
Circling= ipsilateral
Proprioception= contralateral
NOTE:
Vestibular dysfunction is always ipsilateral, cerebella dysfunction tends to be contralateral
Seizure= FOREbrain
Canine neurological exam:
4 parts?
> General exam
- History
- Observe animal approaching
- Normal -> Confused/disorientated -> Depressed -> Stuporous -> Comatose
- Weakness (affects coordinarion BUT not strength)/ataxia?
Head and cranial nerves
- Neurological tests e.g. Menace response
- Facial paralysis (symmetry)
Trunk exam
- Identify focal regions of pain
- Panniculus response (pinch skin to stimulate skin twitch)
- Spinal manipulation/palpation
Limb evaluation
Canine neurological exam:
4 parts?
> General exam
- History
- Observe animal approaching
- Normal -> Confused/disorientated -> Depressed -> Stuporous -> Comatose
- Weakness (affects coordinarion BUT not strength)/ataxia?
Head and cranial nerves
- Neurological tests e.g. Menace response
- Facial paralysis (symmetry)
Trunk exam
- Identify focal regions of pain
- Panniculus response (pinch skin to stimulate skin twitch)
- Spinal manipulation/palpation
Limb evaluation
- Need to assess:
* Proprioception (knuckling/paw repositioning)
* Sensation
* Segmental reflexes
* Muscles mass/tone
- Myotatic/ECR reflex (percuss ECR muscle to achieve reflex)
- UMN/LMN (see separate flashcard)
- Squeeze toes (tests sensation and withdrawal strength)
- Perineal refelex (stimulate perineal region to elicit anal sphincter constriction)
Lesion localisation:
Explain upper and lower motor neurone classifications?
UMN:
- Slow muscle atrophy
- High tone
- Increased/normal reflexes
LMN:
- Rapid muscle atrophy
- Low tone
- Reduced reflexes
Canine neurological examination=
4 parts?
> General exam
- History
- Observe animal approaching
- Normal -> Confused/disorientated -> Depressed -> Stuporous -> Comatose
- Weakness (affects coordinarion BUT not strength)/ataxia?
Head and cranial nerves
- Neurological tests e.g. Menace response
- Facial paralysis (symmetry)
Trunk exam
- Identify focal regions of pain
- Panniculus response (pinch skin to stimulate skin twitch)
- Spinal manipulation/palpation
Limb evaluation
- Need to assess:
* Proprioception (knuckling/paw repositioning)
* Sensation
* Segmental reflexes
* Muscles mass/tone
- Myotatic/ECR reflex (percuss ECR muscle to achieve reflex)
- UMN/LMN (see separate flashcard)
- Squeeze toes (tests sensation and withdrawal strength)
- Perineal refelex (stimulate perineal region to elicit anal sphincter constriction)
Anticonvulsant mechanisms?
- ) Alter intrinsic membrane properties
- primarily Na+ channels - ) Increase inhibitory transmitter function
- primarily in the GABA system
- SEE separate flaschard - ) Decrease excitatory transmitter function
- primarily in the glutamate system
NOTE:
Glutamate= excitatory neurotransmitter and binds to receptors, including NMDA and AMPA receptors
GABA= inhibitory neurotransmitter
Anticonvulsants:
How can inhibitory function be increased?
c
Equine neurological exam:
How can each of the cranial nerves be tested?
- ) CN1 (Olfactory)
- Difficult to tell deficit - ) CN2 (Optic)
- Menace response (blink and withdraw head)
- Open palm instead of moving hand towards face, reduces airflow
3.) CN3 (Oculomotor)
- Constrict pupil
AND
4.) CN4 (Trochlear)
AND
6.) CN6 (Abducens)
- Eye moves around in socket
- Moves eye when head moved and then returns to original focus point
- ) CN5 (Trigeminal)
- Sensation of eye and around face - ## ) CN7 (Facial
- ) CN8 (Vestibulocochl.)
- ) CN9 Glossopharyn.)
- ) CN10 (Vagus)
- ) CN11 (Accessory)
- ) CN12 (Hypoglossal)
Equine neurological exam:
How can each of the cranial nerves be tested?
- ) CN1 (Olfactory)
- Difficult to tell deficit - ) CN2 (Optic)
- Menace response (blink and withdraw head)
- Open palm instead of moving hand towards face, reduces airflow
3.) CN3 (Oculomotor)
- Constrict pupil
AND
4.) CN4 (Trochlear)
AND
6.) CN6 (Abducens)
- Eye moves around in socket
- Moves eye when head moved and then returns to original focus point
- ) CN5 (Trigeminal)
- Sensation of eye and around face - ## ) CN7 (Facial
- ) CN8 (Vestibulocochl.)
- ) CN9 Glossopharyn.)
- ) CN10 (Vagus)
- ) CN11 (Accessory)
- ) CN12 (Hypoglossal)
Equine neurological exam:
How can each of the cranial nerves be tested?
- ) CN1 (Olfactory)
- Difficult to tell deficit - ) CN2 (Optic)
- Menace response (blink and withdraw head)
- Open palm instead of moving hand towards face, reduces airflow
3.) CN3 (Oculomotor)
- Constrict pupil
AND
4.) CN4 (Trochlear)
AND
6.) CN6 (Abducens)
- Eye moves around in socket
- Moves eye when head moved and then returns to original focus point
- ) CN5 (Trigeminal)
- Sensation of eye and around face - ) CN7 (Facial
- Facial symmetry (eye level, muzzle)
- Superficial nerve so easily damaged
- Loses tone on side of dysfunctional nerve SO muzzle deviates towards normal side - ) CN8 (Vestibulocochl.)
- Hearing: Loud bang
- Vestibular component: head tilt - ) CN9 (Glossopharyn.)
- Pull tongue out, horse should retract it (tone), check for damage (hard to pull out= good tone)
- Pharynx should allow swallowing - ) CN10 (Vagus)
- Difficult to assess unless obvious abnormalities - ) CN11 (Accessory)
- Check neck masculature tone - ) CN12 (Hypoglossal)
- Chewing/swallowing requires various nerves
- Masculature of tongue
Barbiturates: Mode of action? Metabolised? Half-life? Toxicity? Example?
> Mode of action:
- Bind to GABA receptor-Chloride ion channel complex
= potentiate GABA
> Metabolised by:
Liver, enzyme induction
> Half-life:
Long
> Toxicity:
Sedation, nystagmus, ataxia, polydipsia, polyphagia
Example: = Phenobarbital Dog: first choice drug Cats: THE drug of choice SE: Used if BDZs are inadequate - Least toxic (possibly), least expensive, most used BUT - Can cause liver issues and so requires monitoring
Phenobarbital vs Impitoin:
Phenobarbital is gradually being replaced- Impitoin is cheaper in long-run as liver doesn’t need to be monitored (although more expensive initially)
Benzodiazepines: Mode of action? Metabolised? Toxicity? Examples?
> Mode of action:
- Bind to GABA(small)A receptors
= facilitate endogenous GABA effects
- Also used for sedative-hypnotic, anxiolytic, muscle relaxant, and appetite stimulating effects
> Metabolized by:
the liver, glucuronidated and eliminated in urine
> Limited toxicity: sedation, CV and respiratory depression at high levels
> Examples:
- Diazepam
- SE: Drug of choice in all animals (BUT very short half-life in animals)
- Clonazepam
SE: Used for this
Bromide (K+, Na+ bromide): Mode of action? Half-life? Toxicity? Example?
> Mode of action:
- Competes with Cl- in the Cl- channel
= Distributed through the body like Cl-
> Half-life:
Very long
Dog: 25-46 days, 2-3 months to steady state
> Toxicity:
Gastric irritation, sedation, ataxia
Imepitoin (Pexion):
Mode of action?
> Mode of action:
- Potentiates the amplitude of γ -aminobutyric acid (GABA)-evoked currents by acting at the benzodiazepines(BZD) recognition site of the GABA-A receptor
- In contrast to clinically used BDZ ligands: Imepitoin (Pexion) is a low-affinity partial agonist with low intrinsic activity
Equine neurological exam:
What signs may indicate ataxia in horses?
- Foot placement different each time
- Swaying, unstable, staggering
- Blindfolding: increases ataxia (NOTE: alters gait, even in normal horses)
What are the main classes of antiepileptic drugs for veterinary medicine?
- ) Barbiturates
e. g. phenobarbital - ) Benzodiazepines
e. g. Diazepam, Clonazepam - ) Bromide
e. g. Na/K bromide
4.) Imepitoin (Pexion)
Equine neurological exam:
Observations from a distance?
> Cerebral abnormalities
- Intention tremor (when attempting precise movement)
- Head tilt
> Abnormal wake/sleep patterns
Equine neurological exam:
Assessment at walk?
- Observe walk: WALK- ataxia should be present at this speed
- Turn horse in circles: right turn should cause right leg to cross underneath them (ataxia: find this hard, pivot on hind legs and L over-reaches)- unilateral defects possible SO circle in both directions
Examples of ruminant diseases with neurological presentation?
> MANY, including:
- Milk fever
- Hypomagnesemia
- BSE
How can a neurological exam in farm animals be completed?
> History
- Acute/chronic/trauma?
- Other aniamls in herd with problems?
- Environment
LOCOMOTION > Walk - Circle - Straight line - Backwards
HEAD > Symmetry - Strabsimus - Nystagmus - Facial drooping > Palpebral reflex > Corneal reflex > Vestibular eye drop response - Eye movement when head turned and then return to original position - Observe sclera at same time (should be white) > Menace response > PLR - BUT dark environment not always available - Slows down in hypocalcaemia
ORAL CAVITY
> Oral cavity inspection
- Pull tongue and cow should pull tongue back
- Abnormal= soft, floppy tongue
- Swallow reflex: should swallow once tongue is released
BODY > Panniculus reflex > Perineal reflex > Lift tail - Should feel resistance from cow
In addition, for SHEEP:
> Knuckling reflex (tests proprioception)
- Animal should correct itself when leg is placed on fetlock
> Wheelbarrowing (tests proprioception)
- Lift hind legs slightly and sheep should take several steps (backwards/ forwards/to the side)
- Can also do this in calves
> Pedal withdrawal
- Pinch between claws and animal should withdraw leg
- NOTE: Can perform this in cow IN CRUSH or in calf when calving
Clinical examples of peripheral nerve disorders in cattle?
HINDLIMB
>
FORELIMB
Clinical examples of peripheral nerve disorders in cattle?
HINDLIMB
> Sciatic nerve
- Starts as sciatic nerve and turns into perineal and tibial nerve towards the back
- Lumbosacral plexus consists of lumbar nerves and large foetus may compress these against lumbosacral joint- may damage gluteal or obturator nerve
- Calving may damage this
> Obturator nerve
- May be damaged in calving if calf’s forelimbs are spread out
- Lying down with splayed legs
> Femoral nerve
- Dog- sitting calf, can not sit up
- Common in newly-born calves which have had an assisted calving
FORELIMB
> Suprascapular nerve
> Radial nerve
Where are Schwann cells found?
Where are oligodendrocytes found?
No Schwann cells in CNS
NO oligodendrocytes in PNS
Which cell is a macrophage cell found in the CNS?
Microglia
What are the conglomerations of grey matter deep within the cerebrum and cerebellum called?
Nuclei
What are the conglomerations of grey matter deep within the cerebrum and cerebellum called?
Nuclei
What are the conglomerations of grey matter deep within the cerebrum and cerebellum called?
Nuclei
Structure of the eyelids?
> Eyelid has 3 layers:
- Inner= Conjunctiva
- Middle= Tarsal plate (fibrous for structure)
- Outer= skin
- Leading edge= series of glands (tarsal/meiglobian glands) which form part of tear film
SEE IMAGE 213
Muscles of the eyelid?
SEE IMAGE 214
SEE PAPER FLASHCARD
- When shocked:
Pupils dilate, eyelids retract - Orbicularis oculi = CLOSES eye- anchored laterally to skull to stop muscle of eyelid moving independently
Third eyelid (nictitating membrane)?
- Protective function
- Medial part of anterior orbit
- No skin: folded mucous membrane
- Not in primates
Layer of cartilage- strcutre
Wrapped around cartilage at base= nictitating gland, produces part of tear film
SEE IMAGE
> General anaesthetic:
Globe retracts and third eyelid may flick across and makes it difficult to examine eye
Function of the eyelids?
- Protects eyeball
- Mechanically removes debris
- (Conjunctival surface) produces components of the tear film
- Wipes cornea to distribute tear film
NOTE: Eyelids closed in puppies until 10-14 days (as they are under-developed)
Anatomy and function of the conjunctiva?
Conjunctival surfaces?
= mucous membrane
Monolayer of columnar epithelial cells (goblet cells producing mucin are in this epithelial layer)
Conjunctiva does not cover cornea, globe ‘pokes ‘through
1 Palpebral conjunctive- lines inner surface of upper eyelid
2 Fornix- reflection of 1
Edge of cornea= limbus
Ventral aspect: 1= palpebral conjunctiva
3 anterior surface of third eyelid, 4 posterior surface of third eyelid
5 bulba conjunctiva (eyeball= bulba)
Bulba conjunctiva= relatively avascular
Palprebral conjunctiva= more vascular thatn bulba conjunctiva
Outer non keratinized epithelium with goblet cells
Underlying stroma with lymphocytes and histiocytes
C.A.L.T. is important component of this layer
Deep fibrous layer of connective tissue, nerves and blood vessels- rich vascular supply with lymphatic drainage
Bulbar conjunctiva: That part of the conjunctiva, a clear membrane of the eye, which covers the outer surface of the eye. The other part of the conjunctiva is the palpebral conjunctiva, which lines the inside of the eyelids.
Examination of the eyelids?
Blinking ?
Menace test
Touch medial canthus region
“False blink”- third eyelid movement
Incomplete blink in some brachycephalics
Touch medial canthus region to assess afferent pathway (cranial nerve 5)- tests sensation without touching and potentially damaging the eye
Skin disease ?
Alopecia, dermatitis, crusting, ulceration, chronic pigmentation/thickening
Tear staining?
Normal in some breeds “tear staining syndrome”
Excess lacrimation- painful eye conditions
Epiphora: (non painful) tear overflow
Check for eyelid position
Look for extra hairs, masses, swellings
Meibomian glands
“grey line”
SEE IMAGE on slide 28
Examine palpebral conjunctival surface (look UNDER eyelids)
What is entropion?
= a condition in which the eyelid is rolled inward against the eyeball
Conditions of cilia?
- ) Ectopic cilium
- ) Distichiasis
- ) Trichiasis
Examination of conjunctiva?
Colour – semi-transparent, variable pigment
Compare bulbar conjunctiva to palpebral conjunctiva
Ocular discharge- mucoid, mucopurulent, serous, porphyrin-stained, haemorrhagic
Abnormal colour- jaundice, cyanosis, toxaemia
Swelling- chemosis
Adhesions
Petechiae/ subconjunctival haemorrhage
“Conjunctivitis”- which vessels ?
Yellow- may be jaundice (may be systemic)
Examination of the eyelids?
> Blinking (Facial nerve):
- Menace test
- Touch medial canthus region (Trigeminal nerve, tests sensation without touching/damaging the eye)
NOTE:
- “False blink”- third eyelid movement across eye
- Incomplete blink in some brachycephalics
> Skin disease:
- Alopecia, dermatitis, crusting, ulceration, chronic pigmentation/ thickening
> Tear staining:
- Excess lacrimation- painful eye conditions
- Epiphora: (non painful) tear overflow
NOTE:
- Normal in some breeds (“tear staining syndrome”)
> Other things to check:
- Eyelid position
- Look for extra hairs, masses, swellings
- Meibomian glands
“grey line”
SEE IMAGE 215
- UNDER eyelids: examine palpebral conjunctival surface
> Cilia conditions
- See separate flashcard
Conditions of cilia?
- ) Ectopic cilium
- Eyelash growing abnormally out of meibomian gland and growing through conjunctiva (painful, can cause ulceration) - ) Distichiasis
- Extra row of eyelashes - ) Trichiasis
- Eyelashes grow from upper eyelid but (due to laxity) can touch the globe
SEE IMAGE 216
Anatomy and function of the conjunctiva?
Conjunctival surfaces?
= mucous membrane
Monolayer of columnar epithelial cells (goblet cells producing mucin are in this epithelial layer)
Conjunctiva does not cover cornea, globe ‘pokes ‘through
1 Palpebral conjunctive- lines inner surface of upper eyelid
2 Fornix- reflection of 1
Edge of cornea= limbus
Ventral aspect: 1= palpebral conjunctiva
3 anterior surface of third eyelid, 4 posterior surface of third eyelid
5 bulba conjunctiva (eyeball= bulba)
Bulba conjunctiva= relatively avascular
Palprebral conjunctiva= more vascular thatn bulba conjunctiva (SO more pink)
Bulba: covers anterior surface of globe and ends at limbus, relatviely transparent, avascular
Palpebral: surface of upper and lower lid and outer face of third eyelid, more vascular so more pink
Outer non keratinized epithelium with goblet cells
Underlying stroma with lymphocytes and histiocytes
C.A.L.T. is important component of this layer
Deep fibrous layer of connective tissue, nerves and blood vessels- rich vascular supply with lymphatic drainage
Bulbar conjunctiva: That part of the conjunctiva, a clear membrane of the eye, which covers the outer surface of the eye. The other part of the conjunctiva is the palpebral conjunctiva, which lines the inside of the eyelids.
Conditions of cilia?
- ) Ectopic cilium
- Eyelash growing abnormally out of meibomian gland and growing through conjunctiva (painful, can cause ulceration) - ) Distichiasis
- Extra row of eyelashes - ) Trichiasis
- Eyelashes grow from upper eyelid but (due to laxity) can touch the globe
- ALSO:
Hairy caruncle, hairs turning away from the face
SEE IMAGE 216
Examination of conjunctiva?
> Colour
- Normal: semi-transparent, variable pigment
- Abnormal: jaundice (yellow, may be systemic), cyanosis, toxaemia
> Compare bulbar to palpebral conjunctiva
> Ocular discharge
- Mucoid, mucopurulent, serous, porphyrin-stained, haemorrhagic
> Swelling (= chemosis)
> Adhesions
> Petechiae/ subconjunctival haemorrhage
> “Conjunctivitis”- which vessels ?
> METHODS to examine conjunctiva:
- Cytology
(Inflammation) - Bacteriology
(Infection) - Virology
(Viral infection)
Conditions of the third eyelid?
- Prolapse of nictitating gland (cherry-eyed)
- Scrolling of nictitating gland (third eyelid)- cartilage grow faster than the membrane around it
Conditions of the third eyelid?
- Prolapse of nictitating gland (cherry-eyed)
- Scrolling of nictitating membrane (third eyelid)- cartilage grows faster than the membrane around it
Nasolacrimal system
Drainage of ocular system
Glands producing tears (major galnd= nasolacrmial gladn)
Sits on dorsal art of globe, under conjuntiva
Dorsolateral part of eye (under conjunctiva)- produces major lart of tear film
Within third eyelid:
Gland of third eyelid produces aqueous part of tears (nictitiating gland)
Tarsal produces lipid layer of tear film
Draingage; tear film escapes by evaporation or by entering nasolacrimal duct (lacrimal puncta in upper and loewer lid)- join together and duct enters through orbital bone and ends up in nasal cavity
Third eyelid (nictitating membrane)?
- Protective function
- Medial part of anterior orbit
- No skin: folded mucous membrane
- Not in primates
Layer of cartilage- structure
Wrapped around cartilage at base= nictitating gland, produces part of tear film
SEE IMAGE 217
> General anaesthetic:
Globe retracts and third eyelid may flick across and makes it difficult to examine eye
Anatomy and function of the conjunctiva?
Conjunctival surfaces?
= mucous membrane
Monolayer of columnar epithelial cells (this epithelial layer contains goblet cells which produce mucin)
CONJUNCTIVAL SURFACES=
> Palpebral conjunctiva
Lines inner surface of upper/lower eyelid AND outer face of third eyelid
More vascular than bulba conjunctiva (SO more pink)
> Fornix
Palpebral conjunctiva reflects back on itself
Prevents material entering the orbit
> Anterior surface of third eyelid
> Posterior surface of third eyelid
> Bulba conjunctiva
Covers anterior side of globe and ends at limbus
Relatively avascular (SO relatively transparent)
SEE IMAGE 218
ANATOMY AND FUNCTION OF CONJUNCTIVA
> Outer non keratinized epithelium with goblet cells
> Underlying stroma with lymphocytes and histiocytes (defence mechanism which can react to infection)
> C.A.L.T. (Conjunctiva associated lymphoid tissue) is important component of this layer (immunological response)
> Deep fibrous layer of connective tissue, nerves and blood vessels- rich vascular supply with lymphatic drainage
> PROTECTS eye
SUMMARY:
Bulbar conjunctiva: clear membrane of the eye, which covers the outer surface of the eye
Palpebral conjunctiva, which lines the inside of the eyelids
What is entropion?
= a condition in which the eyelid is rolled inward against the eyeball
NOTE:
‘Diamond eye’ =
- Extreme form of ectropion of lower lateral lid
Explain structure and function of the Nasolacrimal system?
= Drainage of ocular system
- Glands producing tears (major gland= nasolacrimal gland)
Dorsolateral part of eye (under conjunctiva)- produces major part of tear film - Within third eyelid:
Gland of third eyelid produces aqueous part of tears (nictitiating gland) - Tarsal gland (Meibomian gland) produces lipid layer of tear film
- Drainage: tear film escapes by evaporation OR by entering nasolacrimal duct (via lacrimal puncta in upper and lower lid)- duct enters through orbital bone and ends up in nasal cavity
Nasolacrimal examination?
> Identify puncta
> Flush NL duct
- Use fluorescein dye to prove that the nasolacrimal system is patent
> Dacryocystorhinography
Contrast agents and radiography to show whole nasolacrimal system
Eyes in different dog breeds?
Fighting breeds= eyes mostly covered (for protection)
Explain structure and function of the Nasolacrimal system?
= Drainage of ocular system
- Glands producing tears (major gland= lacrimal gland)
Dorsolateral part of eye (under conjunctiva)- produces major part of tear film - Within third eyelid:
Gland of third eyelid produces aqueous part of tears (nictitiating gland) - Tarsal gland (Meibomian gland) produces lipid layer of tear film
- Drainage: tear film escapes by evaporation OR by entering nasolacrimal duct (via lacrimal puncta in upper and lower lid)- duct enters through orbital bone and ends up in nasal cavity
SEE IMAGE 219
What does the tear film consist of and how is this produced?
> Lacrimal gland:
Produces majority of tear film
> Nictitating gland:
Produces aqueous part of tear film
> Meibomian/Tarsal gland:
Produces lipid layer of tear film
SEE IMAGE 219
Structure of the pre-corneal tear film?
L.A.M.E. ->
Lipid- produced by meibomian glands 0.1um
Aqueous 7um thickness (volume = ?)
Mucin- produced by conjunctival goblet cells 0.04um
Epithelium
Function of the pre-corneal tear film?
Extremely smooth optical surface
Nutrition and protection of the cornea
Lipid- ‘oil on water’- stabilises the tear film between the lids
Aqueous components include defence mechanisms e.g. IgA
Mucin binds tear film to epithelium
Cornea is avascular
Lipid- corneal health- oil creates surface tension. Tear film would come over edge of eyelid without it
Examination of the pre-corneal tear film?
Corneal reflection
Schirmer tear test
Tear film break-up time
Looks at quantity of tears being produced by animal= Schirmer
Tear film- checks quality
Corneal reflection- SEE NEXT SLIDE- bright and shiny eyes show that it is healthy
Schrirmer tear-test- small fold created in paper and retract eyelid, place in conjuncgival pocket and leave for a minute- read result which is generated by capillary action
What produces the pre-corneaal tear film?
> Meibomian/Tarsal gland:
Produces lipid layer of tear film
> Nictitating gland:
Produces aqueous part of tear film
> Lacrimal gland:
Produces majority of tear film
SEE IMAGE 219
Adnexa
ALL SLIDES ARE COMPLETED
c
Structure of the pre-corneal tear film?
L.A.M.E.=
> Lipid (outer layer)
- Produced by: meibomian glands
- 0.1um thickness
- Helps to prevent evaporation
> Aqueous (majority)
- Produced by: nictitating gland
- 7um thickness
> Mucin (inner layer)
- Produced by: conjunctival goblet cells
- 0.04um thickens
- Binds tear film to corneal surface (‘glue’)
> Epithelium of cornea
- the 3 layers bind to this
- microvilli increase SA= allows tear film to attach more completely
SEE IMAGE 220
Function of the pre-corneal tear film?
- Smooth optical surface
- Nutrition and protection of the cornea (cornear is avascular)
- Lipid stabilises the tear film between the lids (‘oil on water’ creates surfacee tension to prevent tear film from coming over edge of eyelids)
- Aqueous contains defence mechanisms e.g. IgA
- Mucin binds tear film to epithelium
Examination of the pre-corneal tear film?
Explain the most commonly-used test?
- SCHIRMER TEAR TEST (assesses quantity) - Tear film break-up time (assesses quality) - Corneal reflection (bright/shiny= healthy)
> Most commonly-used test= Schirmer tear test:
- Small fold created in paper
- Retract eyelid and place in conjunctival pocket
- Leave for a minute- read result (mm/min) which is generated by capillary action
Explain the conditions which are associated with abnormal tear production?
> Over-production
a. ) Lacrimation
- Associated with inflammatory condition
b. ) Epiphora
- Associated with eye position
- NOT associated with infection/inflammation
> Under-production
= Keratoconjunctivitis sicca (KCS)
- Dry eye
Explain the structure of the sclera and limbus?
- Opaque sclera is largest portion of the outer coat of the eye
= Composed of collagen/fibroblasts
= gives eyeball its shape - Limbus
= line between cornea and sclera
= source of stem cells (part of corneal repair) - Tenon’s capsule
= thin membrane around eyeball from the optic nerve to the limbus - Episclera
= thin layer of tissue that lies between the conjunctiva and the sclera
Gross anatomy of the cornea?
Microscopic anatomy of the cornea?
GROSS ANATOMY:
> Domed- curvature enable refractive power, allows light to be focused on back of eye (NOT just lens which focuses)
> Made of collagen BUT is transparent
> Herbivores: horizontal corneas
> Land AND water animals: flat corneas, rely more on lens for focusing
MICROSCOPIC ANATOMY: > Outer surface= EPITHELIUM (thinner), stratified squamous epithelium > Basement membrane= Contains hemi-desomosomes > Middle surface= STROMA > Basement membrane (Descemet's layer) > Inner surface= ENDOTHELIUM (thicker)
SEE IMAGE 221
Microanatomy of the corneal epithelium?
SEE IMAGE 226
- Basal part of epithelium= columnar cells layer
- Nerve fibres: within epithelium and anterior stroma= highly-innervated (used for protection as it can become painful)
- Migrating cells: cells change shape and as they form and multiply, daughter cells pushed towards surface and change shape- become wing cells (lose organelles and die)- this constant migration is to prevent bacteria/viruses from adhering to surface of eye
- Microvilli increase SA
- SEE IMAGE 227
Microanatomy of the corneal stroma?
> Fibroblasts and fibrils are arranged in layers, with VERY regular pattern to allow us to see through it (light refracts through), despite being made of collagen
If it becomes disorganized, this is a sign of corneal disease/scarring, gaps may appear
Highly sensitive- protective function
SEE IMAGE 228
Microanatomy of the corneal endothelium?
> Inner surface of cornea is a barrier: allows nutrition, metabolites, oxygen etc. to diffue through but prevents transfer of excessive water (cornea is avascular to allow transparency and must also be slightly dehydrated)
Corneal oedema= excess water enters cornea which makes it cloudy due to causing a disorganized structure
Less restorative function than epithelium
Active transport pumps out water to prevent corneal stroma becoming opaque
SEE IMAGE 229
How can depth of an ulcer be estimated?
36
How can you identify where a lesion is in the eye?
- Superficial vessels crossing limbus
- ‘Tree-roots’ have budded off from capillaries of conjunctival cells and have grown over limbus/corneal cells
- Cover cornea and sclera SO must be more anterior to these structures
SEE IMAGE 230
Explain corneal healing?
1.) Epithelial healing:
- Good restorative abilities
- Epithelialisation:
* Cells divide (mitosis)
* Then cells slide
* Then cells ‘glue’ themselves down across deficit
2.) Stromal healing:
- Rely on fibroplasia (takes time) and vascularisation (blood vessels must grow as part of this healing process)
3.) Endothelial healing:
Poor healing properties
NOTE: Complex interaction of proteases, growth factors, and cytokines Epithelial cells, stromal keratocytes, inflammatory cells and lacrimal glands
What is debridement?
Epithelium starts to detach from surface beneath
SO remove unhealthy epithelium to allow new epithelium to grow
BUT not the only treatment for corneal ulcers (usually associated with deep or infected ulcers)
SEE IMAGE 224
Causes of corneal ulcers?
> Lid lesions > Eyelash lesions > Trauma - Lacerations - Abrasions - Foreign body - Dystrophies/Degenerations - Infections - Keratconjunctivitis sicca (KCS)
How can depth of a corneal ulcer be estimated?
SEE IMAGE 225
> Superficial ulcer=
- Looks less severe
- More painful (majority of nerve fibres are in the anterior part)
> Deep ulcer=
- Less painful
- Greater risk of damaging eye further
NOTE: Descemetocoel= Deep ulcer (in Descemet's membrane) - In danger of rupturing - Emergency
What is debridement?
Epithelium starts to detach from surface beneath
SO remove unhealthy epithelium to allow new epithelium to grow
BUT not the only treatment for corneal ulcers (usually associated with deep or infected ulcers)
SEE IMAGE 224
Lens:
Location?
Features?
> Location:
- Posterior to iris/pupil
- Anterior to vitreous humour
> Features
Tear film and cornea
ALL SLIDES ARE COMPLETED
c
Lens:
Location?
Features?
Gross anatomy?
> Location:
- Posterior to iris/pupil
- Anterior to vitreous humour
> Features:
- Transparent
- Avascular
- Aqueous humour: provides oxygen/ glucose by diffusion
- Vitreous humour: minor role in nutrition
- No nerves (only part of eye not innervated)
- Refractive, biconvex (cornea also helps to focus image)
> Gross anatomy - Lens capsule: * Anterior epithelium * No posterior epithelium * Cortex (outer) * Nucleus (inner)- zones according to age (embryonic on inside) * Lens zonules: suspensory ligaments - Anterior and posterior poles, suture lines SEE IMAGE 231
SUMMARY:
Outer area is called the cortex, inner area is called the nucleus which is subdivided according to age (oldest on the inside)
Explain lens embryology?
- Develops from surface ectoderm
- Lens vesicle thickens and then detaches- forming hollow sphere within developing optic cup
Explain lens fibres?
- Lens grows throughout life, concentric
- New lens fibres form from anterior epithelium at lens equator, these secondary lens fibres wrap around embryonic nucleus (NOTE: No posterior epithelium in adult lens)
SEE IMAGE 232 - Lens is a sphere of monolayer of epithelium
- Epithelial cells elongate on posterior side to form primary lens fibres and fill space to convert hollow sphere into solid sphere- embryonic lens nucleus
- SO no posterior epithelium because it has formed lens nucleus
Clinical relevance of the lens development?
- Lens= viable and active
- Oldest part of lens: Centre (nucleus)
- Newest part of lens: Outer lens (cortex)
- Lens damage may cause cataract
- Early life damage:
cataract formed in part of lens that has already grown (e.g. centre)= tend not to progress, remain static (normal, clear lens fibres formed around this) - later life damage: cataract formed in cortex= tend to be more progressive
Lens:
Suture lines?
- Fibres: thick centres, tapered ends
- Not enough space for fibres to meet in single point SO meet in Y-shape (upright Y in anterior lens, upside-down Y in posterior lens)
Explain lens zonules?
- Ligaments surround and suspend lens 360 degrees, holding it in place
- Originate from: Ciliary body, attach to: lens capsule
SEE IMAGE 233
Blood supply to the lens?
> Adult lens
- Avascular, nutrition from aqueous (majority of supply) and vitreous
(SUMMARY: lens nutrition taken over from primary vitreous by aqueous humour as lens develops)
> Developing
- Extensive vascular network provides nutrition until humour forms later, supply stops as it develops (avasculariy ensures transparent adult lens)
- Divided into anterior and posterior:
a. ) Anterior blood supply: - originates from anterior rim of developing optic cup
- forms pupillary membrane: solid sheet which covers anterior lens, no pupil during development
b. ) Posterior blood supply: - Network of blood vessels within vitreous: called ‘primary vitreous’
- Main blood vessel (hyaloid artery) enters optic cup with optic nerve and branched into network of blood vessels which wrap around back of lens
SEE IMAGE 241
Anterior blood supply:
Normal development?
Abnormal development?
> Normal development:
- Pupillary membrane and blood vessels regress
- PUPIL forms (i.e. a hole within iris)
> Abnormal development:
- INCOMPLETE regression
- Strands of tissue remain on iris and/or span pupil
= Persistent pupillary membrane (PPM)
SEE IMAGE 234
Posterior blood supply:
Normal development?
Abnormal development?
> Normal development:
- Regresses- leaves tiny remnant of artery on back of lens (pig’s tail- generally not visible)
Abnormal development:
- Blood supply in vitreous persists and ‘thickens’
- Forms vascular plaque and possible cataract
- Persistent hyperplastic primary vitreous (PHPV)
SEE IMAGE 235
- Persistent hyaloid artery
SEE IMAGE 243
= appears as cataract OR intraocular haemorrhage
Problems of the lens?
- ) Transparency change:
- Cataract
- Nuclear sclerosis - ) Change in position
NOTE: Use distant ophthalmology to distinguish between nuclear sclerosis and cataract by observing tapetal reflection
Explain lens accommodation?
Explain how age and lens accommodation are related to each other?
ACCOMMODATION:
Accommodation= ability of lens to change thickness and focus for near and far objects
- Lens changes shape to focus eye on near/distant objects
- Close objects: Ciliary body contracts= tension on lens zonules= lens stretched
(Short distance: lens must be fat to bend light rays into image on retina quickly enough) - Distant objects: Ciliary body relaxes= less tension on lens zonules= lens relaxes
AGE AND ACCOMMODATION: > Young lens: - Firm but flexible - Lens nodules easily alter tension on lens SO can easily focus > Older lens - ‘Stiffer’ - Difficult to focus on near objects = presbyopia
Composition of the lens?
- 35% protein (soluble/insoluble proteins)
- 65% water
- Stable composition maintains transparency
- Change in composition= CATARACT develops
Explain glucose metabolism?
- Several pathways
- Most important: ANAEROBIC metabolism
- Aerobic glucose metabolism less important- Citric acid cycle
- Hexose monophosphate shunt
- Sorbitol pathway- Important in diabetes mellitus (see separate flaschard)
> SUMMARY:
Multiple pathways for glucose metabolism in the lens and most is anaerobic
Examination of the lens?
- Dark room
- Peripheral lens covered by iris: Dilate the pupil (tropicamide, Mydriacyl)
- Light source: pen torch, ophthalmoscope- pick up tapetal reflex
- Magnification: Direct ophthalmoscope
SUMMARY:
- Dark room
- Dilate pupil
- Light source
- Magnification
Function of distant direct ophthalmoscopy?
- Compare pupil size/shape
- Identify opacities
NOTE: Cataract blocks tapetal reflection BUT nuclear sclerosis does not
Problems of the lens?
- ) Transparency change:
a. ) Cataract
b. ) Nuclear sclerosis - ) Change in position
NOTE: Use distant ophthalmology to distinguish between nuclear sclerosis and cataract by observing tapetal reflection- cataract blocks fundic reflex, nuclear sclerosis does not
Problems of the lens:
1.) a.) What is cataract?
Causes of this?
Classification of cataract?
= ANY LENS OPACITY
- Part/all of lens becomes more opaque, due to change in normal protein/water ratio
> Causes:
- Hereditary
- Non-hereditary
- Congenital
- Nutritional
- Diabetes mellitus
- Trauma
> Classification:
- Aetiology
- Stage of development
- Age of development
- Position within lens
- Consistency
Problems of the lens:
1.) a.) Stages of development of cataract?
> Incipient - Tapetal reflex: Large > Immature (incomplete) - Tapetal reflex: reduced but still present > Mature (complete) - Tapetal reflex: not present > Hypermature - Tapetal reflex: may be partially restored (due to cataract liquefication and resorption with loss of lens volume and capsule wrinkling and plaques)
SUMMARY:
Can have immature (incomplete, partial fundic reflex) OR mature (complete, no fundic reflex) cataract
SEE IMAGE 236 (2 parts)
Problems of the lens:
2.) Change in position?
> LENS LUXATION - Lens zonules break - Lens starts to ‘wobble’ as zonular attachments loosen a.) Anterior lens luxation Lens drops backwards
Lens blocks flow of aqueous humour
Pressure inside eye increases rapidly causing acute secondary glaucoma
LENS SUBLUXATION
Painful
Problems of the lens:
1.) b.) Explain nuclear sclerosis?
How does this differ in older/younger dogs?
- Lens grows throughout life (secondary fibres added around outside of lens)
- BUT Finite space within eye
- SO compresses nucleus
- Nucleus becomes hard and SCLEROTIC
- Compressed lens fibres refract light rays differently: lens appears ‘milky blue’
- Normal age-related change (due to lens growing throughout life)
= NOT a cataract - BUT causes presbyopia
> YOUNG dog:
- Large nucleus
- Thin cortex
> OLDER dog:
- Compressed nucleus
- Thicker cortex
SEE IMAGE 237
How to determine between cataract and nuclear sclerosis?
> Distant direct ophthalmology to observe tapetal reflection:
- Cataract= blocks tapetal reflection
- Nuclear sclerosis= does NOT block tapetal reflection
Problems of the lens:
2.) Change in position?
> LENS LUXATION - Lens zonules break - Lens starts to ‘wobble’ as zonular attachments loosen - Often causes retinal detachment > Lens subluxation= dislocates out of position (painful- pressure in lens increases) SEE IMAGE 238 > Anterior lens luxation= Lens drops forwards SEE IMAGE 239 > Anterior lens luxation AND glaucoma= - Lens blocks flow of aqueous humour - Pressure inside eye increases - Causes acute secondary glaucoma SEE IMAGE 240 > Anterior lens luxation AND glaucoma treatment: - Emergency treatment to remove luxated lens - Enucleation may be required
How to determine between cataract and nuclear sclerosis?
> Distant direct ophthalmology to observe tapetal reflection:
- Cataract= blocks tapetal reflection
- Nuclear sclerosis= does NOT block tapetal reflection
What are Uveitis and Glaucoma?
What are the symptoms of these?
> Uveitis=
Inflammation of uvea
> Glaucoma=
Increased intraocular pressure which damages the optic nerve
SYMPTOMS:
> Painful, cloudy, red eyes which can become quickly blind
Anatomy of the uveal tract?
- Iris (anterior part of uveal tract)
- Ciliary body
- Choroid
Contains:
- Muscles (aid accommodation)
- Nerves and blood vessels (- Highly vascular/innervated)
- Fibrocytes
- Aelanocytes (melanin= thick/dark, protective function)
- Source of blood products for the eye:
- Erythrocytes, * Leucocytes
- Fibrin
- Antibodies (Blood products: substances going through the body BUT must not enter ocular media/compartments of eye)
NOTE:
- Neuro-retina= transparent layer
- Layer of uveal tract= fusion on mesoderm and neuroectoderm
- Back of iris= double layer (forwards projection of neuro-retina)
Structure of the iris?
What does iris colour depend on?
Function of the iris?
STRUCTURE
- Anterior surface: divided into pupillary zone and ciliary zone
- Anterior border layer (NOT epithelium)
- Stroma and sphincter muscles (contract to constrict pupil)
- Posterior epithelial layer and dilator muscles (double layer at back)
- Surrounds pupil:
- Circular sphincter muscles contract to constrict pupil
- Dilator muscles on edge counteract this by dilating pupil
- Double epithelium right up to pupil (often double-pigmentation around pupil edge)
IRIS COLOUR
- Number of melanocytes
- Thickness of anterior border
FUNCTION
- Controls pupil size: controls amount of light entering eye
- Constriction of pupil: increases depth of focus for near vision
NOTE:
- Constrictor muscles allow wider pupil in dim light and smaller as light gets brighter
- Constrictor muscles run along PS branch of oculomotor nerve (miosis)
- Autonomic nerves involved in dilator function
- SEE separate flashcards for PLR
Pupil shape in different species?
> Dogs: similar to primates
Cat: vertical slit- different shape/arrangement of sphinctor mscles so can see better at night BUT not very good fine-focusing in daytime)
Horse: horizontal slit/dome- better view of landscape
NOTE: Predators have forward-facing eyes but laterally placed eyes of prey allow them to see all around
Structure of the ciliary body?
- Behind the iris route- can not see as clinician
SEE IMAGE 244
Function of the ciliary body?
- Production/ drainage of aqueous humour
- Generates intraocular pressure
- Anchors lens nodules
- Accomodation
- Constitutes blood-aqueous barrier
- Vasculature/ innervation to anterior segment
Structure and function of aqueous humour?
Aqueous production?
Aqueous flow?
> Structure and function=
- Transparent fluid
- Fills: anterior chamber, pupil and posterior chamber
- Ultrafiltrate which resembles plasma
- Much lower concentration of proteins, immunoglobulins, enzymes and lipids
- Supplies avascular lens and cornea with nutrients and removes waste
- Circulates within anterior chamber due to temperature difference between air-cooled cornea and iris
> Aqueous production=
- Ciliary body processes
- Large surface area
- Channels in outer non-pigmented epithelium through which aqueous forms
- 3 methods of transport:
1.) Osmotic diffusion of aqueous humour
2.) Ultrafiltration (due to pressure)
3.) Active transport (ATPase, secretion of Na which then draws water in and is controlled by carbonic anhydrase)
NOTE:
Carbonic anhydrase inhibitor drugs can be used as medical treatments for chronic glaucomas
BUT consider: Reducing aqueous reduces nutritional supply to lens and cornea
SEE IMAGE 245
> Flow of aqueous humour=
Aqueous produced through ciliary epithelium (towards back of eye- posterior chamber). Aqueous is produced, enters posterior chamber and pushes through where zonules are, through pupil, fills anterior chamber and perculates out back on itself through drainage angle (forward extension of ciliary body- at route of iris)
Anatomy of the choroid?
> Choroid= thin but highly metabolically active
- Suprachoroidea
- Large vessels
- Medium vessels
- Tapetum
- Choriocapillaris
- Bruch’s membrane
- Choroid and retina are intimately linked
- Several layers between RPE and sclera
- Tepetum is part of uveal tract (part of the choroid)
- Tepetal tissue helps with sight in the dark
SEE IMAGE 263
Examination of uveal tract- iris and aqueous humour?
- PLR
- Clear anterior chamber
- Bright iris
- Clear optical axis
NOTE: big species-specific differences
NOTE:
Heterochromia=
Different pigmentation colours within iris, usually in animals with differnt spots of fur colour
Ocular nutrition/immunology:
Blood-aqueous barrier to systemic disease
> Blood-aqueous barrier
- Tight junctions between the non pigmented epithelial cells acts as a barrier to free diffusion- prevent antibodies from entering eye
NOTE: Vascular supply within uveal tract is tight: allows oxygen/glucose but not blood to enter eye
> If this barrier breaks down then the protein leaks into the clear ocular media
> Antibodies enter the aqueous and the tissue may be rejected as ‘non self’
Examination of anterior chamber?
Look at eye from all angles
Iris is bowing forwards uniformly and is swollen. Pressure of aqueous pushing forwards
Front chamber is filled with fluid
Slide 37
Examination of uveal tract: signs of uveitis?
> Pain, photophobia, lacrimation, visual impairment
Red eye- conjunctival hyperaemia, ciliary injection
Swollen dull iris, rubeosis iridis, miosis
Aqueous flare, hyopyon, hyphaema
Corneal oedema, vascularisation
Synechiae, secondary glaucoma
Cataract
Retinal detachment, retinal degeneration, optic nerve atrophy
SUMMARY
As eye becomes more damaged, uveal tract may become more dysfunctional and develop a secondary cataract
Explain Glaucoma?
Causes?
Examination for glaucoma?
NOTE:
Uvea and Glaucoma
ALL SLIDES ARE COMPLETED
EXPLANATION: > Intraocular pressure depends on: - Ocular rigidity - Volume of aqueous (= constant production and drainage)
> Increased pressure: damages the optic nerve head SO disrupts microcirculation and axoplasmic flow within retinal ganglion cell axons
> CAUSES:
- Causes of primary glaucoma:
- goniodysgenesis
- myocilin (a protein)
- Causes of secondary glaucoma:
- primary lens luxation
- uveitis
- neoplasia
- intraocular haemorrhage
- pigmentary glaucoma
EXAMINATION:
> ‘Cardinal’ Signs
> Tonometry
- Measures pressure
- Schiotz tonometry has been superseded by applanation/re-bound tonometry
> Gonioscopy
- Looks at drainage angle to see if eye is predisposed to glaucoma
Location of the retina?
- Neural layer (inner)
- Between: vitreous humour (internally) and choroid/sclera (externally)
NOTE: Sclera (outer), choroid (middle), retina (inner) THEN vitreous humour
Explain the fundus and its structures?
Species differences?
= part of posterior section of eye, viewed with ophthalmoscope (NOT necessarily an anatomical structure)
> Structures:
- Optic disc (where optic nerve enters back of eye)
- Tapetal fundus (shiny, dorsal part of eye)
- Non-tapetal fundus
- Retinal vasculature
SEE IMAGE 246
SEE IMAGE 247
> Species differences:
a. ) Holangiotic=
- Retinal blood vessels supply whole retina (extend to edges)
- e.g. dog, cat, cow, sheep, goat
b. ) Paurangiotic=
- retinal blood vessels supply small focal area of retina
e. g. horse
SEE IMAGE 248
Nutrition for the retina?
> 2 sources:
- Retinal blood vessels (from carotid arteries)
- Choroidal blood vessels
NOTE: retina is very metbaolicalyl acatice (high blood supply/oxygen delivary here) SO systemic disease may have ocular signs
EXAMPLE:
High blood pressure may show as haemorrhage in retina/vitreous when viewing fundus
Nutrition for the retina?
> 2 sources:
- Retinal blood vessels (from carotid arteries)
- Choroidal blood vessels
NOTE: retina is very metabolically active (high blood supply/oxygen delivery here) SO systemic disease may have ocular signs
EXAMPLE:
High blood pressure may show as haemorrhage in retina/vitreous when viewing fundus
Structure of tapetum?
Function of tapetum?
> Structure:
- Part of choroid
- Lies behind retina
- Shiny, reflective
> Function:
- Reflects light rays so retina receives light twice (increases visual acuity)
Explain the anatomy of the retina?
> 10 layers > Simplified into 2 layers: 1.) Retinal pigment epithelium (RPE) = 1 layer 2.) Neurosensory layer = 9 layers SEE IMAGE 249
1.) RPE:
SEE separate flashcard for function
2.) Neurosensory retina (the important layers):
- Photoreceptor layer (rod and cones)- next to RPE
- Outer nuclear layer (always widest layer of dots on histology examples)
- Retinal ganglion cells
- Nerve fibre layer
- The other layers are interconnecting neural cells
SEE IMAGE 250
Normal variations of tapetum?
> Consider overall pigment in individual
- Coat colour linked to iris colour
- Iris colour linked to fundus colour
- Fundus colour determined by colour of different layers
- Fundus colour determines fundic reflex colour
> Typical colour combinations:
- Dog, herbivore: strong coat colour, brown iris, overall yellow/green/blue fundus with obvious tapetum
- Cat: strong coat colour, dark yellow iris, overall yellow fundus with obvious tapetum
- Reduced pigment in coat typically associated with blue iris and reddish/brown or red/white appearance of fundus
What colour is choroid in humans?
What colour is fundus in puppies?
Fundus colour in animals with reduced pigment?
Humans:
ALWAYS red
Puppies:
Turquoise
Reduced pigment:
Often different colours of fundus
Tapetal vs non-tapetal retina?
SEE IMAGE 251
Non-tapetal fundus surrounds tapetal fundus
Tapetal= non-pigmented retina Non-tapetal= pigmented retina
Non
Tapetal:
Tapetum is extra layer within coroid
Structure of RPE?
Function of retinal pigment epithelium (RPE)?
> Structure?
Outermost, singl layer of cells
- In front of tapetum
- Pigmented in ventral fundus where tapetum is absent
- Non-pigmented in dorsal fundus where tapetum is present (allows tapetum to be seen)
> Function?
- Retinal integrity and function
- Photoreceptors embedded within RPE- provides rods/cones with nutrition
SEE IMAGE 252
Function of retina?
Describe the photoreceptor layer?
Function of rods and cones?
Phototransduction: Photoreceptors in retina contain visual pigments. Absorb light ray (photoreceptors become hyperpolarised) and converts into nerve impulse which travels through neurosensroy layers to ganglion cells, to nerve axons and up optic nerve to visual cortex
> Phototransduction occurs: light energy converted to nerve impulse
> RODS and CONES: contain visual pigments
- Cones=
* Colour vision
* Visual acuity
- Rods=
* Night vision
NOTE: nuclei of rods and cones: in outer nuclear layer- appears as thick layer of black dots (= rod and cone nuclei)
- SEE IMAGE 250
- Light hits rods/cones = initiates complex series of reactions= generates nerve impulse
Explain ganglion cell layer and nerve fibre layer?
> Ganglion cells form the last layer of neural cells- Lie adjacent to vitreous
- Axons of ganglion cells form nerve fibre layer
- Nerve fibres converge on optic disc, forming the optic nerve
Location of the optic nerve on a view of the fundus?
More ventral than usually shown
Structure of the vitreous humour?
Function of the vitreous humour?
> Structure:
- Gel between lens and retina
- Largest ocular structure
- Avascular and NO innervation
- Transparent
- 99% water, 1% protein/cells
> Function:
- Shock absorber (protects retina)
- Maintains intraocular anatomy
- Removes waste products
Common conditions associated with vitreous humour?
generalised Progressive Retinal Atrophy (gPRA)
Collie Eye Anomaly
Retinal detachment
How does retinal detachment occur?
Clinical signs?
How does it appear on an ultrasound image?
> Retina is only strongly attached:
- Around optic disk
- Ora ciliaris retinae (peripheral retina)
> Detachment occurs between:
- Neurosensory retina
- and RPE
> Clinical signs: - Reduced vision/blindness - Dilated pupils - Blood vessels visible just behind pupil - Grey ‘billowing’ effect NOTE: not painful SEE IMAGE 253
> On an ultrasound image:
- V-shaped (looks like the wings of a bird)
SEE IMAGE 254
Common conditions associated with vitreous humour?
- ) generalised Progressive Retinal Atrophy (gPRA)
- Group of conditions in which photoreceptors (rods and cones) fail to develop normally (dysplasia) or degenerate prematurely (degeneration)
- Gradual loss of vision (typically night vision lost first)
- No treatment
- Fundus view: blood vessels visible AND hyper-reflectivity of tapetum BECAUSE neurosensory retina is thinner ALSO pale optic disc BECAUSE optic nerve atrophy - ) Collie Eye Anomaly (CEA)
- ) Retinal detachment
Common conditions associated with vitreous humour?
- ) generalised Progressive Retinal Atrophy (gPRA)
- Group of conditions in which photoreceptors (rods and cones) fail to develop normally (dysplasia) or degenerate prematurely (degeneration)
- Gradual loss of vision (typically night vision lost first)
- No treatment
- Fundus view: blood vessels visible AND hyper-reflectivity of tapetum BfECAUSE neurosensory retina is thinner ALSO pale optic disc BECAUSE optic nerve atrophy - ) Collie Eye Anomaly (CEA)
- Congential
- Choroidal hypoplasia (choroid doesn’t form properly) seen as ‘pale patch’ dorsolateral to optic disc
- Bilateral but can be very asymmetrical
- Fundus view: thin choroid creates pale patch (whiteness is the sclera)
- Varying effect on vision
- Screen parents before breeding, genetic tests - ) Retinal detachment
- See separate flashcard
Optic nerve:
- Regions?
> 3 regions:
- Intraocular portion (can be directly observed in vivo)
- Retrobulbar portion (in orbit)
- Intracranial portion
NOTE: Optic nerve= afferent pathway to visual cortex
Optic nerve:
- CT scan?
SEE IMAGE 256
Not a straight line- bends, as this allows flexibility for eyeball to move around
How does the optic nerve leave the globe?
- Sclera is tough SO optic nerve passes through lamina cribosa at posterior pole of globe
Sieve-like area in sclera
A weak point, sensitive to increased intraocular pressure (glaucoma)
May be myelinated (dog) or non-myelinated (cat)
Affects appearance of optic disc as seen with ophthalmoscopy
How does the optic nerve leave the globe?
> Sclera is tough SO optic nerve passes through LAMINA CRIBOSA at posterior pole of globe
> Lamina cribosa=
Sieve-like area in sclera
- A weak point, sensitive to increased intraocular pressure (glaucoma) SO glaucoma causes pain and blindness very quickly
- May be myelinated (dog) or non-myelinated (cat)
= Affects appearance of optic disc as seen with ophthalmoscopy
SEE IMAGE 248
NOTE: Extra myelination is a normal variation (shows as big, fluffy disc) – e.g. golden retrievers
SEE IMAGE 255
Fundus variations between breeds?
SEE IMAGE 257 Less pigmented coat= Smaller tapetum Less pigmented choroid Less pigmented RPE
Senses of ear?
Double sense organ=
Auditory: Hearing
Equilibrium: Balance
Parts of the ear- boundaries to each of them?
External ear
Middle ear
Inner ear (contains vestibulocochlear organ)
SEE IMAGE 258
Outer to middle=
Ear drum
Middle to inner=
Tympanic membrane
Vestibulocochlear: vestibular= balance, cochlear= hearing
Parts of the ear- boundaries to each of them?
1.) External ear
2.) Middle ear
3.) Inner ear
SEE IMAGE 258
Structures for hearing= in all parts
Vestibulocochlear organ=
in inner ear
Outer to middle=
Ear drum (tympanic membrane)
Middle to inner=
Oval and roudn windows
Vestibulocochlear: vestibular= balance, cochlear= hearing
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External ear:
What is the pinna moved by?
NOTE: Pinna (usually vertical) runs into external acoustic meatus (usually horizontal)
5 sets of muscles:
- Rostral
- Dorsal
- Caudal
- Ventral
- Intrinsic
External ear: > What is the pinna moved by? > Function? > Parts: - Tragus - External acoustic meatus?
NOTE: Pinna (usually vertical) runs into external acoustic meatus (usually horizontal)
5 sets of muscles: - Rostral - Caudal - Dorsal - Ventral - Intrinsic Innervation: facial nerve
FUNCTION:
- Receives soundwaves and conducts them to tympanic membrane (eardrum)
> Tragus:
- Helps brain to locate origin of the sound
External acoustic meatus (horizontal):
- Cartilaginous tunnel connecting outer ear and tympanic membrane
- Lined with stratified squamous epithelium and contains sebaceous glands which produce earwax
- Epithelial cells in EAM migrate outwards to move debris trapped in cerumen (earwax) out of the EAM
Middle and inner ear:
Location?
Temporal bone structure?
> BOTH enclosed within temporal bone
> Temporal bone is made of 3 bones: 1.) Squamous - Extends into zygomatic arch 2.) Tympanic - Contains middle ear 3.) Petrosal (arrow-head shape) - Contains inner ear - Contains IAM (facial/vestibulocochlear nerves travel through this) - No marrow cavity- prevents resonance/echo SEE IMAGE 259
Middle ear?
AND tympanic cavity?
MIDDLE EAR
- Tympanic cavity within the tympanic bulla
- Three auditory ossicles, two muscles
- Opening of Eustachian tube (auditory tube)- balances pressure between middle ear and back of throat when we swallow
TYMPANIC CAVITY
- Normally air-filled, with epithelial mucosal lining
- Within the tympanic part of the temporal bone
- Contains dorsally the three auricular ossicles
- Middle part includes tympanic membrane in the lateral wall of the cavity and opens into auditory tube
- Ventral part is the tympanic bulla:
- Enhances hearing at low and high frequencies
- Two windows in the medial wall:
1. ) Vestibular (oval) window covered by the stapes
2. ) Cochlear (round) window closed by the secondary tympanic membrane
What is otits media?
Group of inflammatory diseases of middle ear
Tympanic membrane (eardrum):
Structure?
Function?
> Separates external from middle ear
STRUCTURE
> Three layers:
1.) External epithelial lining (ectoderm)
2.) Connective tissue with collagen and elastic fibres & fibrocartilagineous ring (tympanic ring) (mesoderm)
3.) Inner mucous membrane towards tympanic cavity (endoderm)
> Highly vascularised
> Sensory innervation: Facial and vagus nerves
FUNCTION:
- Insertion of malleus (hammer)
- Transmits sound waves from air onto the auditory ossicles
3 middle ear bones:
What are auditory ossicles?
Structure of auditory ossicles?
Function of auditory ossicles?
> Series of three bones in middle ear
STRUCTURE
- Very dense bone (no resonant chambers) BUT light (able to move easily)
SEE IMAGE 260
SEE IMAGE 261
FUNCTION:
> Transmits vibrations from tympanic membrane across the tympanic cavity to the vestibular foramen leading to the inner ear
> Air – bone coupling
> Bone – liquid coupling
> Reduction of sound reflection
> Initiation of a wave in the perilymph of the inner ear
Malleus/incus joint= slightly flexible
Incus/stapes joint= moves easily
Auditory ossicle evolution?
NOT a learning objective (just read through this)
Incus and malleus develop from 1st pharyngeal arch mesoderm (mammals).
Stapes develops from 2nd pharyngeal arch mesoderm (reptiles, mammals).
Incus and malleus is just in mammals (mammals have 3 ear ossicles), stapes is in all species
The mandible is derived from the 1st arch, also the incus and malleus have evolved from 1st arch bones (quadrate & articular) which make up the complex jaw seen in reptiles.
Hence a defining feature of mammals is three ear ossicles.
In reptiles and birds:
columella (=stapes)
extracolumella (inflexible cartilage connection between columella and tympanum)
No tympanic membrane in snakes
Nerves in the middle ear?
SEE IMAGE slide 49
Cr.N.VII
runs through facial canal, which is open to the tympanic cavity
innervates M. stapedius via stapedial n.
Gives off the chorda tympani
Taste to rostral 2/3 or tongue, also heat and mechanoreception.
Joins lingual br. of mandibular n (cr.n.V).
Tympanic nerve (branch of Cr.N. IX)
Parasymp. supply for parotid and zygomatic salivary glands.
Postganglionic sympathetic fibres from cr.cervical ganglion.
Join the ophthalmic nerve for sympathetic supply of the eye.
Damage leads to Horner’s syndrome (dog / cat).
Inflammation in the middle ear can damage these nerves
2 middle ear muscles:
Structure?
Function?
STRUCTURE > Two striated tonic muscles: 1.) Stapedius m. - Attached to stapes 2.) Tensor tympani m. - Attached to malleus SEE IMAGE 262
FUNCTION
> Involved in attenuation of vibrations:
- Loud noise= reflex contraction to protect inner ear (more effective if CONTINUOUS loud noise)
- Blocks animal’s own sound e.g. barking (feed-forward control)
Auditory (Eustachian) Tube:
Structure and function?
Perissodactyls?
Nerves and Arteries Adjacent to the Guttural Pouch?
STRUCTURE AND FUNCTION:
> Connects nasopharynx and ear= air pressure equalisation
- Bulla -> Eustachian tube -> Pharynx
> Usually closed- opens when swallowing= allows air pressure to balance
PERISSODACTYLS:
> Important in perissodactyls
(guttural pouch)
- Bulla -> Eustachian tube -> Guttoral pouch -> Pharynx
(NOTE: no protection between guttoral pouch and vessels connected to it so infections can spread easily)
NERVES/ARTERIES ADJACENT TO GUTTORAL POUCH:
Facial n.(limited contact)
Glossopharyngeal n.
Vagus n.
Accessory spinal n.
Hypoglossal n.
Postganglionic axons from cr.cervical ganglion.
External carotid a.
Internal carotid a.
Ear/hearing:
Reptiles?
Sound in water?
Fish?
REPTILES
All reptiles except snakes:
Middle ear.
Single ossicle (stapes, or columella).
Tympanic membrane may be inside an ear canal.
Snakes:
No middle ear.
Outer end of the columella is attached to the quadrate bone of the jaw.
Able to sense ground vibrations very well.
Deaf to sound in the air.
SOUND IN WATER
Sound reflects off a water-air interface.
Good for detecting fish with swim bladders.
Different water densities can reflect sound.
Problem for sonar in submarines.
Can hide under water layers.
Sound travels well in water.
Whale song can be heard over tens of miles.
FISH
Fish can hear.
Lots of species differences.
The mechanoreceptors of the lateral line are the origin of the mechanoreceptors of the ear – they both measure vibration.
No external or middle ears.
Do have a vestibular (balance) organ that represents their inner ear.
Very primitive cochlea (“lagena”)
They hear via bone vibration:
Lateral lines.
Otoliths.
Swim bladders connected to inner ear via auditory “Weberian” ossicles, derived from vertebrae.
Sharks have a duct from the skin to the inner ear.
Nerves in the middle ear?
SEE IMAGE slide 49
> FACIAL NERVE
- Runs through facial canal, which is open to the tympanic cavity
innervates M. stapedius via stapedial n.
Gives off the chorda tympani
Taste to rostral 2/3 or tongue, also heat and mechanoreception.
Joins lingual br. of mandibular n (cr.n.V).
Tympanic nerve (branch of Cr.N. IX)
Parasymp. supply for parotid and zygomatic salivary glands.
Postganglionic sympathetic fibres from cr.cervical ganglion.
Join the ophthalmic nerve for sympathetic supply of the eye.
Damage leads to Horner’s syndrome (dog / cat).
Inflammation in the middle ear can damage these nerves
Nerves in the middle ear?
SEE IMAGE slide 49
> FACIAL NERVE
- Runs through facial canal, which is open to the tympanic cavity
- Innervates M. stapedius via stapedial n.
- Gives off the chorda tympani
- Taste to rostral 2/3 or tongue, also heat and mechanoreception.
- Joins lingual br. of mandibular n (cr.n.V).
> TYMPANIC NERVE (branch of Cr.N. IX)
- Parasymp. supply for parotid and zygomatic salivary glands.
-
Postganglionic sympathetic fibres from cr.cervical ganglion.
- Join the ophthalmic nerve for sympathetic supply of the eye
- Damage leads to Horner’s syndrome (dog / cat).
NOTE: Inflammation in the middle ear can damage these nerves
VEstiulocochlear organ
Bath duck shape
How is the transformation of sound from air to fluid completed?
The transformation of sound from air to fluid is aided by two facts :
- Tympanic membrane has a greater surface than the oval window
- The hammer is a longer lever than the anvil.
Due to these facts the force at the oval window is ~20x greater that at the tympanic
membrane.
This matches the impedance of air and fluid – fluid needs more force to move it, so the levers of the ossicles multiply the force from tympanic membrane to oval window.
Hair cell structure?
Hairs cells have long cilia projecting from their apex.
A single kinocilium develops first, then moves to edge of the hair cell.
Microvilli on the hair cell develop into stereocilia, using the kinocillium as a guide to their height.
In mammals the kinocilium degenerates once the stereocilia are mature.
Note:
The stepped arrangement of the stereocilia.
The afferent and efferent nerve supply.
Inner AND outer hair cells
Lots of cilia at different heights on the same cell
Can move around but tips are joined by proteins and so must all move together
Afferent AND EFFERENT supply (have a feedback mechanism)
SEE IMAGE slide 16
All hair cells have an internal skeleton of actin filaments.
Stereocilia are stiff and hinge at their connection with the cell membrane.
Prestin is a contractile protein within the cell membrane of outer hair cells.
Movement of stereocilia depolarizes the cell.
Prestin contracts when the cell is depolarized.
Makes the stereocilia move.
Thus bending the stereocilia makes them bend in response = amplification of the movement.
Slide 18
Inner hair cells (IHC):
Afferent innervation, 1 IHC : 10 axons.
Myelinated.
Form radial afferents making up 95% of the neurons.
Go to cochlear nuclei in the medulla.
Efferent* innervation from ipsilateral olivary nuclei.
Outer hair cells (OHC):
Afferent innervation, 10 OHC : 1 axon.
Mainly efferent* innervation from both sides of the olivary nuclei.
These form spiral non-myelinated axons.
OHC are contractile cells which amplify local vibrations**.
Length of cell inversely proportional to the frequency it responds to.
*Efferents change the sensitivity of the hair cells.
**Important for the cochlear amplifier and reverse transduction.
All cell bodies in the spiral ganglion.
Ear and hearing 1
SLIDES TO COMPLETE:
6-12
(Read through these- not on learning objectives)
Complete
Describe vestibular ataxia?
- Asymmetric ataxia
- Resultant from abnormal vestibular function
- Head tilt
- Paw turned over
- Ataxia
NOTE:
Central vestibular problems are worse then peripheral vestibular problems
Peripheral can usually be managed, central are more serious
What are the 2 major components of the vestibular system?
- Peripheral receptor organs
- Central co-ordinating pathways
Vestibular system:
Location?
Inside petrous temporal bone
INNER ear
Function of vestibular system?
BALANCE etc.
NOT hearing
Separate functional units of vestibular system?
1.) Semicircular canals
- Dynamic information
2.) Otolith organs
- Static information
a.) Utricle (horizontal)
b.) Saccule
(vertical)
Explain the separate functional units of vestibular system?
- 3 semi-circular canals (dynamic info.)- each in different orientation (x/y/z axes to follow movement in 3 planes) widen into ampullae- filled with endolymph
- Vestibule connects all ampullae of the semicircular canals
- Inside ampullae= cupula structures which have hair cells which are embedded unto the ampulla organs
- Movement of endolymph inside semi circular canals (in SAME direction as movement of head) causes movement of stereocilia which sends signals to brain about plane of movement
SEE IMAGE 264 - Semicircular canals, one on each side of head- brain matched information from both sides and interprets this (tight left turn: semi-circular canals firing more on LHS then RHS and so brain can rate this and understand that it is movement in left direction)
SEE IMAGE 266
IN ADDITION TO THIS
= Otilith organs
Otilith organs (static info.):
- ) Saccule (vertical info.)
- ) Utricle (horizontal info.)
- Gelatinous mass contains calcium carbonate structures
- Movement of plane causes crystals to move within this which causes hair cells to move
SEE IMAGE 265 - Hair cells act as transducers: mechanoreceptor
- Gentle movement in one direction causes hair cells to move in this direction and distortion of hair cells distorts mechanically gated K+ channels creating depolarisation
- Movement in other direction causes hyperpolarisation of calcium channels
NOTE: longest of the hair cells (kino-cilia) must be disturbed or depolarisation action - Respond to both static and dynamic information
Explain nystagmus?
- Visual cues help to maintain equilibrium
- Mechanism to ensure visual stabilisation during movement
- Eye movement is saccadic (fixation then rapid movement)
Nystagmus= regularsaccadic movement
Explain central pathways?
Explain central projections?
> Central pathways:
- Vestibular cochlear nerve has nuclei which conduct information into brain and then into other parts of the body
- Central pathways take information from these structures and into the brain
- Vestibular cochlear nerve has nuclei which conduct info into brain and then to other parts of body
SEE IMAGE 267
> Central projections:
- From vestibular nuclei in medulla
- Projection from medial geniculate nucleus on both sides which go alongside auditory info (vestibulo-cochlear nerve) and then to cerebral cortex
- Branches to nuclei of CN III, IV and VI
- AND projection going to reticular formation
- Vestibulospinal tract (part of the extrapyramidal system- involuntary movement)
- All info courses ipsilaterally to cerebellum and then into body on ipsilateral side
Explain vestibulospinal tract?
How does information travel from the vestibular system in the inner ear to the limbs?
VS tract takes info through CNS and out into muscles
When pushed: extensors/flexors change to respond appropriately to info coming from VS tract
SEE IMAGE 268
- Information in semi circular canals
T- Travels from vestibular ganglion, leading to vestibular nerve - Goes through lateral vestibular nucleus and into lateral vestibular spinal tract (LVST)
- LVST courses all te way through into lumbar regions
- Allows signals to reach all limb muscles to achieve positional equilibrium
SEE IMAGE 269
Normal function of vestibulospinal system:
Effects when body is pushed?
- Body is pushed
- Vestibulospinal system produces lean AWAY from that side
Cerebellar component of vestibular system?
= Flocculonodular lobe
- Ipse lateral projection with efferent pathway
- Strong cerebellar control of vestibular movements
- Takes info from vestibular system and rates this and connects this to visual information (visual tracking and oculomotor control all linked to vestibular movements)
- ALSO involved in maintaining equilibrium
- Can see vestibular signs with cerebellar disease (e.g. nystagmus) (cross-over of signs) but may show paradoxical head tilt
- Nystagmus
Cerebellar has contralateral control SO head tilt would be on opposite side to dysfunction of cerebellum
Are cerebellar and vestibular system ipselateral or contralareral?
Cerebellar= contralateral control
(head tilt on opposite side to dysfunction of cerebellum)
Vestibular system=
ipsilateral control
NOTE: may only see positional strabismus when head is moved as vestibular system is ipsilateral
