Physiology Flashcards
Where is CSF produced and how often is it replaced daily?
Produced by secretory epithelium of the choroid plexus in the ventricles
Amounts to ~150ml volume that is replaced 3-4x daily
CSF is mainly composed of…?
Water
What are the 3 major functions of CSF?
- Mechanical: protection of the brain
- Homeostatic: pH affects pulmonary ventilation and cerebral blood flow
- Circulation: exchanges water, amino acids and ions between the brain and blood while removing metabolic waste
How is a CSF sample taken?
By lumbar puncture at the L3/4 or L4/5 IV disc level
as the spinal cord ends at L2 so any higher could risk damaging it
Describe a normal CSF sample
Clear/colourless
Contains little protein (15-45mg/dl)
Contains little Igs (1-5 cells/ml)
The brain ventricles and the spinal canal develop from the X at around week Y of embryonic development
X - neural tube/canal
Y - week 4
Embryology: how is the choroid plexus formed?
- Developing arteries invaginate the roof of the ventricle to form the choroid fissure
- Involuted ependymal cells and the vessels enlarge into villi that form the choroid plexus
Describe the structure of a choroid plexus
- Highly vascularised
- Contains an inner blood capillary
- Outer layer of ependymal cells joined by tight junctions
CSF is secreted by the ependymal cells from their basolateral/apical end?
Apical
CSF secretion involves the transport of ions from blood and out of the ependymal cells. What ions are taken in from the blood? In exchange for?
Na+ and Cl- are taken in from the blood in exchange for HCO3- and H+
H2O follows Na+ drags water into the cells by osmosis
Na+, Cl- and H2O are secreted by the ependymal cells in the CSF
Describe relative concentrations of... -K+ -Na+ -Cl- -Glucose -Protein ... in the CSF in comparison to plasma concentrations
Lower concentrations of K+, glucose and protein
Higher concentrations of Na+ and Cl-
The production of CSF is a passive process as it does not require energy. T/F?
False
It is an active secretory process as active transport channels are required to move Na+ and Cl- out of the ependymal cells
Which active transporter is largely responsible for movement of Na+ and Cl- out of the ependymal cells?
The Na+/Cl-/K+ transporter
What are the 4 ventricles of the brain?
Right lateral ventricle
Left lateral ventricle
(Midline) 3rd ventricle
(Midline) 4th ventricle
Name the structure that connects…
- Lateral ventricles to the 3rd ventricle
- 3rd ventricle to the 4th ventricle
- Lateral ventricles to the 3rd ventricle: Foramen of Munro
- 3rd ventricle to the 4th ventricle: Cerebral aqueduct
Describe the circulation of CSF from the ventricles the the subarachnoid space
- CSF is produced by the choroid plexus in the left and right lateral ventricles
- It flows through the foramen of Munro and into the 3rd ventricle
- It joins CSF produced by the choroid plexus in the 3rd ventricle
- CSF flows through the cerebral aqueduct to the 4th ventricle
- It joins CSF produced by the choroid plexus in the 4th ventricle
- A small amount of CSF enters the central spinal canal to cushion the spinal cord but the majority moves into the subarachnoid space
- CSF circulates in the subarachnoid space and is reabsorbed into the dural venous sinuses via the arachnoid granulations into the dura mater
Name the 2 foramen that allow the fourth ventricle to communicate with the subarachnoid space
Foramen Magendie
Foramen Luschka
The blood-CSF barrier prevents free exchange of material between the blood and CSF. Exchange can only occur at…?
Arachnoid granulations in the dural venous sinuses (/superior sagittal sinus (SSS))
The blood-brain barrier prevents free exchange between the blood and the brain tissue. Describe the structure of the blood brain barrier (3)
- Endothelial cells surrounding blood capillaries
- Basal membrane of the endothelial cells
- Astrocyte end feet which hold the endothelial cells in tight apposition (in addition to tight junctions)
State one advantage and one disadvantage of the blood brain barrier
Adv: protects the brain from infections and toxins
Disadv: is the main obstacle for drug delivery to the CNS
List 4 pathologies which can affect the ventricles
- Tumours
- Ventricular haemorrhage (accumulation of blood in the ventricles)
- Hydrocephalus (accumulation of CSF in the ventricles or around the brain)
- Idiopathic intracranial hypertension (increased CSF pressure but no imaging features of hydrocephalus)
How does hydrocephalus appear on imaging?
The ventricles are enlarged due to an imbalance in production and clearance of CSF
What optic pathology can hydrocephalus cause?
Papilloedema (due to increased intracranial pressure)
What is papilloedema?
Swelling of the optic nerve/disc
What is the function of aqueous humor in the anterior segment of the eye?
It is a specialised fluid which nourishes the lens and inner surface of the cornea in the anterior segment of the eye
Describe production and circulation of aqueous humor in the anterior segment of the eye
- Ciliary processes in the ciliary body secrete aqueous humor into the posterior chamber
- Aqueous nourishes the lens then passes through the pupil into the anterior chamber
- It nourishes the internal surface of the cornea
- Aqueous is reabsorbed by the scleral venous sinus/trabecular meshwork/Canal of Schlemm at the iridocorneal angle
What are the 2 types of epithelium cells in the ciliary body?
Pigmented ciliary epithelial cells (PE)
Non-pigmented ciliary epithelial cells (NPE)
How are PE and NPE cells organised to form the ciliary epithelium?
- Inner layer of PE cells are in communication with the blood in the ciliary body
- Outer layer of NPE cells secrete aqueous into the anterior segment
Aqueous secretion involves the transport of ions from blood and out of the NPE cells. What ions are taken in from the blood? In exchange for?
Na+ and Cl- are taken in from the blood by PE cells in exchange for HCO3- and H+
H2O follows Na+ drags water into the cells by osmosis
Na+, Cl- and H2O diffuse into the NPE cells and are secreted into the anterior segment of the eye as aqueous humor
Why is the enzyme carbonic anhydrase (CA) important for aqueous humor production?
CA catalyses the formation of HCO3- and H+ which are exchanged for the intake of Na+ and Cl- into the PE cells
When might carbonic anhydrase inhibitors be used in medicine?
To reduce ocular pressure in glaucoma (as reduced CA will reduce production of aqueous humor)
What causes glaucoma?
Raised intraocular pressure due to an imbalance between the rate of aqueous humor secretion and reabsorption
Each eye is divided into a nasal and a temporal retina. What structure divides the retina in half in this way?
The fovea
centre of the macula, area with greatest density of cones and most acute vision
Which 2 hemiretina pick up images in the left visual field?
What about the right?
Left visual field: left nasal and right temporal retina
Right visual field: right nasal and left temporal retina
Signals from the (temporal/nasal) hemiretina cross over at the optic chiasma to form a left and right optic tract which allow the left and right visual fields to reach the left and right primary visual cortexes separately
Nasal
Light from the right visual field is processed in the upper/lower/left/right primary visual cortex?
Light from the lower visual field is processed in the upper/lower/left/right primary visual cortex?
Light from the RIGHT visual field is processed in the LEFT primary visual cortex?
Light from the LOWER visual field is processed in the UPPER primary visual cortex?
Which ganglion is involved in the visual pathway?
Lateral geniculate nucleus (LGN)
In the primary visual cortex, at what layer are eye specific inputs segregated?
Layer 4C
Each visual cortex receives input from the left and the right eye (as the nasal signals cross sides in the optic chiasma). What is meant by ocular dominance columns? How do they relate to the journey of the signal from the optic chiasma to the visual cortex?
Ocular dominance columns: inputs from each eye remain separate as they travel towards the visual cortex
Eye specific inputs remain in their separate ocular dominance columns until they reach layer 4C of the visual cortex, where they segregate. Subsequent layers of the visual cortex receive inputs from both eyes
How do ocular dominance columns develop?
- During infancy, an axon from both eyes is in contact with a cell in layer 4C of the visual cortex
- One of the axons will dominate and so the other gradually retracts
- This forms the ocular dominance columns
Why can a problem in one eye (monocular deprivation) during infancy result in inability of the brain to process signals from that eye even once the problem is fixed?
- During infancy, an axon from both eyes is in contact with a cell in layer 4C of the visual cortex
- One of the axons will dominate and so the other gradually retracts
- In monocular deprivation, the axon from the non-affected eye will always be the dominant one
- Axons from the affected eye will retract
- Once the problem is fixed, signals will not be processed from the bad eye because there are no axon connections between it and the visual cortex
When tracing single neurons in the lateral geniculate nucleus, describe how the neurons appear different in an eye affected by monocular deprivation vs the normal eye
The neuron from the deprived eye will have less axon branches
What is amblyopia?
Disorder of vision in one eye caused by impaired development of vision in early infancy e.g., due to monocular deprivation
List 2 conditions which can cause amblyopia if they are not corrected in infancy
Congenital cataract
Strabismus (wandering eye)
The retina has many layers but we just need to know 4. What are these?
- Photoreceptors
- Bipolar cells
- Ganglion cells
- Ganglion cell axons
Light coming into the eye must first pass through the ganglion axon, ganglion cell, and bipolar cell layers before reaching the photoreceptors. T/F?
True
The photoreceptor layer then sends the signals back to the bipolar cells
Name and describe 2 interneurons involved in signal processing in the retina
Horizontal cells:
- Receive input from photoreceptors
- Project to other photoreceptors and bipolar cells
Amacrine cells:
- Receive input from bipolar cells
- Project to other bipolar cells, other amacrine cells, and ganglion cells
What is the general function of a photoreceptor?
Name the two types
To convert electromagnetic radiation into neural signals (i.e., phototransduction)
Two types: rods and cones
What are the 3 main regions of the photoreceptor cell?
- Outer segment formed by membranous discs containing photopigment (longer in rods)
- Inner segment containing the cell body
- Synaptic terminals which release the neurotransmitter glutamate onto bipolar cells
Photoreceptors have a more depolarised resting membrane potential (Vm) than other neurons. What is the Vm of a photoreceptor?
~ -20mV
other neurons is ~ -70mV
Why is a photoreceptor’s Vm more positive than other neurons?
Due to the ‘dark current’
What is meant by the ‘dark current’?
In the dark, cGMP-gated Na+ channels are open
Na+ influx and K+ efflux are balanced and so Vm sits at ~20mV between their resting potentials
What happens to Vm when the photoreceptor is exposed to light?
The cGMP-gated Na+ channel closes and the membrane hyperpolarises (i.e., becomes more negative) because K+ efflux now exceeds Na+ influx
It is like a current is turned off
Hyperpolarisation of one photoreceptor can lead to hyperpolarisation of its neighbouring photoreceptors. T/F?
False
Hyperpolarisation is local and graded, so each photoreceptor responds independently
What is rhodopsin?
A visual pigment G-protein coupled receptor found in the membrane discs of the outer segment of rod cells
It is formed by retinal (a vitamin A derivative) and opsin (the actual GPCR)
How does light cause cGMP-gated Na+ channels to close in rod cells?
- Light activates rhodopsin (11-cis-retinal + opsin)
- This converts 11-cis-retinal to all-trans-retinal
- All-trans-retinal activates the G-protein transducin
- Transducin activates cGMP phosphodiesterase
- PDE hydrolyses cGMP which reduces its concentration
- Reduced cGMP concentration results in closure of Na+ channels
Describe amplification of cGMP-gated Na+ channel closure
1 opsin activates 1000 transducin G-proteins to activate a PDE
1 PDE hydrolyses 1000 cGMPs
=> large amplification process
Photoreceptors provide a steady release of the neurotransmitter glutamate to bipolar cells. Is more glutamate released in the dark or the light?
More glutamate is released in the dark as the cell is more depolarised
Visual acuity (i.e., sharpness of vision) is largely determined by what factor?
By photoreceptor spacing
Photoreceptors which are more spaced out increase acuity of vision. T/F?
False
Larger spaces between photoreceptors = less acuity
Photoreceptors closer together = higher acuity
Compare rods and cones in terms of…
- Spacing
- Acuity
- Sensitivity
- Colour vision
Rods:
- Spaced further apart => lower acuity (blurrier vision)
- Higher sensitivity (but can see in the dark)
- Don’t see colour (they don’t need to in the dark)
Cones
- Closer together => higher acuity (sharper vision)
- Lower sensitivity (but can’t see well in the dark)
- Chromatic
Why do rods have a higher sensitivity than cones?
They allow us to see in the dark whereas cones can allow us to see in the light
Rods allow for better dark vision due to their position in the retina. Describe the distribution of rods and cones in the retina
Rods: found around the periphery of the retina
Cones: most concentrated in the fovea and macula in the centre of the retina
Photoreceptors are activated by visible light wavelengths in the electromagnetic spectrum. What wavelengths are detected by... -Blue cones -Green cones -Red cones -Rods ?
- Blue cones: short wavelengths: 380-550 nm
- Green cones: medium wavelengths: 450-650 nm
- Red cones: long wavelengths: 500-700 nm
- Rods: long wavelengths: 400-630 nm
