Lecture 34: CSF Flashcards

1
Q

What are the 2 ‘spaces’ between the meninges?

A
  • Subdural space (thin) lies between dura and arachnoid mater.

Subarachnoid space lies between arachnoid and pia mater, contains CSF, (veins) and arteries, prone to infection (menigitis).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the two ‘types’ of meninges?

A

There are two types of meninges:

  • Dura mater (pachymeninges): a thick, rigid membrane surrounding brain and spinal cord.
  • Cranial dura consists of two layers including a thick periosteal layer and an inner meningeal layer. The two layers are ordinarily adherent, but they split to form venous sinuses.
  • The falx (between heimsphere) and tentorium (between middle cranial fossa separate temporal lobe and cerebellum) are formed by reduplication of the inner meningeal layer.
  • The inner layer of dura extends into the spinal canal where it surrounds the spinal cord and forms the lumbar theca sac.
  • Leptomeninges: consist of two structurally similar layers, include arachnoid (outer layer) and pia (inner layer).
  • Arachnoid is a thin layer of connective tissue that encloses the CSF in the subarachnoid space.
  • Pia is adherent to the surface of the brain and spinal cord.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is CBF?

A

The cerebrospinal fluid (CSF) is the fluid located in ventricles and subarachnoid space around brain and spinal cord.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where is the CSF produced?

A

Most of the CSF is formed by choroid plexus, mainly in the lateral ventricles.

A small amount of CSF is produced directly from the interstitial fluid of the brain by bulk flow along perivascular spaces and along axon tracts.

This involves two processes in series

  • (a) Ultrafiltration across choroidal capillary wall, which depends on hydrostatic pressure in the capillaries;
  • (b) Active secretion by choroidal epithelium (endothelial and epithelial cells of choroid plexus have specific transport systems for a variety of compounds including ions, vitamins, nucleosides, purines, glucose and amino acids).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the Choroid Plexus Structure

A

Fenestrated capillary network surrounded by a single r_ow of epithelial cells_ (part of the blood brain barrier)

Choroid plexus epithelial cells

  • tight junctions between cells
  • contain numerous vesicles, lysosomes
  • ventricular surface of epithelial cells has a brush border of microvilli
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Total CSF volume is usually _______\_

The CSF volume in ventricles is __________\_

A

Total CSF volume is usually ~150ml (can vary from 140 to 270ml in adults). Total CSF volume gradually increases with ­ age.

The CSF volume in ventricles is 12-25ml.

  • Most of the CSF (125ml) is in the subarachnoid space, of which 30-45 ml are in lumbar theca sac.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe how CSF are produced

A

Most of the CSF is formed by choroid plexus, mainly in the lateral ventricles.

This involves two processes in series

(a) Ultrafiltration across choroidal capillary wall (fenestrated), which depends on hydrostatic pressure in the capillaries;
* Fluid is pushed out into the interstitial space from the capillaries
(b) Active secretion by choroidal epithelium (endothelial and epithelial cells of choroid plexus have specific transport systems for a variety of compounds including ions, vitamins, nucleosides, purines, glucose and amino acids).
* The fluid needs to be actively secereted to become the CSF(found outside of the choroidal epithelium) because of the tight junctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

The flow of CSF from ventricles is fascilitated by …….

A

The flow of CSF from ventricles is facilitated by:

  • Hydrostatic pressure created by CSF production in the choroid plexus (major);
  • Arterial pulsations inside cranial cavity;
  • Directional beating of the ependymal cilia.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the direction of flow of the CSF

A

CSF flow follows the following route:

  1. lateral ventricles
  2. via interventricular foramina (foramina of Monro**) ®
  3. third ventricle (midline) ®
  4. via cerebral (Sylvian) aqueduct ®
  5. fourth ventricle ®
  6. via 1 midline foramen (foramen of Magendie) & 2 lateral foramina (foramina of Luschka) ®
  7. subarachnoid space (subarachnoid cisterns surrounding brainstem & subarachnoid space overlying spinal cord surface and brain convexities) ® Virchow-Robin (perivascular) spaces (in depths of cerebral cortex).
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe where/how the CSF are absorbed

A

CSF returns to the vascular system by entering the dural venous sinuses via arachnoid granulations.[2] These are outpouchings of the arachnoid mater into the venous sinuses around the brain, with valves to ensure one-way drainage.

The major route of CSF absorption is via the small arachnoid villi and the larger arachnoid granulations.

The arachnoid villi are herniations of arachnoid membrane through dura mater into lumen of superior sagittal sinus and other cerebral veins.

  • CSF absorption depends on hydrostatic pressure in
  • subarachnoid space
  • CSF absorption is not regulated by any transport process
    • CSF absorption occurs by unidirectional bulk flow.
    • Arachnoid villi act as one-way valves (allow CSF flow into veins), which are kept open (and dependent) by hydrostatic pressure in subarachnoid space.

CSF absorption is not regulated by any transport process.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Label 1 and 5

A

1) Third ventricle
5) Posterior horn of lateral ventricles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the turnover rate of CsF

A

3-4x per day

(600ml/day 0.35ml/min)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Most of the CSF is in the….

A

Subarachnoid space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are Arachnoid villi?

A
  • herniations of arachnoid mater through dura mater into lumen of superior sagittal sinus
  • absorb CSF by unidirectional “bulk flow”
  • function as one-way valves that allow flow of CSF into veins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CSF absorption is proportional to ___________\_

A

CSF absorption is proportional to CSF pressure (65-250 mmH2O).

Therefore, huge increase in CSF production is required to raise intracranial pressure to a level at which production greatly exceeds CSF absorption.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How can a sample of CSF be obtained?

A

A sample of CSF can be obtained from subarachnoid space in lumbar theca sac by lumbar puncture.

  • _Lumbar puncture i_s usually performed using local anaesthesia with patient lying in the left lateral recumbent position (back in a straight line) with their neck, trunk, hips and knees flexed.
  • The needle is inserted into L3/4 intervertebral space. When needle is in subarachnoid space, CSF pressure can be measured with a manometer and a sample of CSF can be removed for laboratory analysis.

CSF sample is most commonly examined for presence of cells (leukocytes, erythrocytes, tumour cells), concentrations of protein and glucose are measured. If infection is suspected (e.g. meningitis), CSF can be cultured. A variety of other tests can be done for special indications.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Which lumbar space do you obtain the CSF from?

A

L3/4 intervertebral space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the normal CSF composition (KNOW THE NUMBERS)

A

Normal cerebrospinal fluid appears clear and colourless:

  • White blood cells <5x106/L (no polymorphs)
  • No neutrophils
  • No red blood cells
  • Protein <0.45g/l
  • Glucose >2.5mmol/l (depends on blood glucose and rate of brain glucose metabolism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How much glucose should there be in CSF?

A

Glucose >2.5mmol/l (depends on blood glucose and rate of brain glucose metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How much WBC should be in the CSF?

A

White blood cells <5x106/L (no polymorphs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How much protein is there in the CSF?

A

Protein <0.45g/l

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does the CSF change in Meningitis?

A
  • ↑ white blood cells (mostly polymorphs)
  • ↑ protein
  • ± ↓ glucose

Normal cerebrospinal fluid appears clear and colourless:

  • White blood cells <5x106/L (no polymorphs)
  • No neutrophils
  • No red blood cells
  • Protein <0.45g/l
  • Glucose >2.5mmol/l (depends on blood glucose and rate of brain glucose metabolism)
23
Q

How does the CSF change in Subarachnoid Haemorrahge?

A
  • ↑ red blood cells
  • “xanthochromia” (yellow discolouration due to red cell breakdown products)

Normal CSF composition (know numbers!)

Normal cerebrospinal fluid appears clear and colourless:

  • White blood cells <5x106/L (no polymorphs)
  • No neutrophils
  • No red blood cells
  • Protein <0.45g/l
  • Glucose >2.5mmol/l (depends on blood glucose and rate of brain glucose metabolism)
24
Q

CSF has…

↑ white blood cells (mostly polymorphs)

↑ protein

± ↓ glucose

What do they have?

A

Meningitis

25
Q

CSF shows..

↑ red blood cells

“xanthochromia” (yellow discolouration due to red cell breakdown products)

What does this person have?

A

Subarachnoid haemorrhage

26
Q

What are the functions of CSF?

A
  • Homeostasis (maintains constant environment for neurons and glia). (it i part of the blood-brain barrier)
    • Blood-brain and blood-CSF barriers preserve homeostasis of the central nervous system by facilitating entry of essential metabolites and removing or excluding toxic or unnecessary metabolites and substances.
  • Mechanical protection for brain. CSF cushions brain from impact within skull vault during movement and external trauma.
  • Counters sudden increases in intracranial pressure. A sudden increase in intracranial pressure forces CSF from the intracranial cavity into spinal canal, which helps to restore intracranial pressure to normal. (e.g. when you cough)
27
Q

What are the functions of the Blood-brain barrier?

A

Functions of Blood-Brain Barrier

Blood brain barrier and blood CSF barrier preserve homeostasis of neurons and glia. These barriers have three functions:

  1. Regulation of ionic balance in the brain
  2. Facilitates selective transport of essential substrates/metabolites (e.g. oxygen, glucose) across endothelial cells into the brain
  3. Barrier against the entry of potentially harmful molecules.
  4. Therefore many metabolites needed by
    brain need to be “selectively”
    transported across the endothelial cells
28
Q

What does the Blood Brain Barrier consist of?

A
  • specialised endothelial cells
  • thick basement membranes
  • astrocytic processes on capillaries
29
Q

Compare the systemic and brain capillaries

A

Endothelial cells in blood brain barrier (CNS) differ from endothelial cells in other organs in several ways:

  • Absence of fenestrations and presence of tight junctions, which limits movement of even small molecules between cells and effectively separates plasma from brain extracellular fluid.
  • Brain specialized endothelial cells have fewer pinocytotic vesicles, thicker basement membranes and more mitochondria (reflecting higher metabolic rate required for active transport systems)
  • Astrocytic foot processes are closely apposed to the abluminal walls of capillaries and have an important role in regulation of ions and volume of the brain.

Blood-CSF barrier is located in the choroid plexus and the meninges. Unlike the capillaries that form the blood brain barrier, the endothelial cells in the choroid plexus are fenestrated, but the barrier is provided by tight junctions between the epithelial cells of the choroid plexus. The epithelial cells in the choroid plexus have many mitochondria.

30
Q

Describe the Transport across the Blood-brain and Blood-CSF barriers

A

There are different mode of transport across BBB, which include:

  • Diffusion (lipid soluble substances such as O2, CO2, alcohol)
  • Active transport (glucose, some a_mino acids_, vitamins, nucleosides)
  • Ion channels
31
Q

What are some factors affecting the pasage of molecules across the BBB

A
  • Molecular weight (size): most small molecules can cross the blood-brain barrier.
  • Lipid solubility: lipid-soluble compounds (e.g. O2, CO2 and lipid soluble drugs) cross BBB readily.
  • Ionisation (electrical charge) at physiological pH.
  • Protein binding: restricts entry into the brain and the CSF.
  • Specific transport system in endothelial cells of some substances (ions, glucose, some amino acids, vitamins and peptides):
  • facilitated diffusion (energy-independent);
  • active transport (energy dependent).
32
Q

What are the 5 ways the BBB can be disrupted?

A

BBB can be disrupted in several ways:

  1. Disruption of tight junctions, leading to passage of molecules between cells.
  2. Disruption (proteolysis) of basement membranes, e.g. inflammatory response in meningitis can cause BBB breakdown, so white cells and protein appear in CSF.
  3. Disruption of endothelial cell-astrocyte interactions.
  4. Altered function of specific transporter mechanisms.
  5. New blood vessels lacking BBB features, e.g. brain tumours have abnormal leaky capillaries, accumulates interstitial fluid (oedema) increases ICP and cause even death (actually due to oedema!).
33
Q

What are some disorders that affect the blood-brain barrier?

A
  • Brain tumours
    • abnormal blood vessels
    • vessels can be “leaky”
    • interstitial fluid accumulates (oedema)
  • Meningitis
    • inflammatory response causes BBB breakdown
    • white cells and protein in the CSF
34
Q

In terms of the intracranial pressure, describe the Measurement of the intracranial pressure

A

1. Measurement of Intracranial Pressure

Normal CSF pressure (in adults) is 65-195mmCSF (or mmH2O), or 5-15mmHg. It is measured by:

  1. Lumbar puncture (patient lying flat on left lateral position)
  2. Intracranial pressure monitoring devices: inserted into a lateral ventricle, or the epidural space.

In the setting of transtentorial herniation, an increase in lumbar CSF pressure lags behind intracranial pressure.

  • Lumbar puncture is a less useful method of measuring intracranial pressure and it’s potentially dangerous.
  • Intracranial pressure monitoring device is safer method.
35
Q

Normal CSF pressure (in adults) is __________\_

A

Normal CSF pressure (in adults) is 65-195mmCSF (or mmH2O), or 5-15mmHg. It is measured by:

  1. Lumbar puncture (patient lying flat on left lateral position)
  2. Intracranial pressure monitoring devices: inserted into a lateral ventricle, or the epidural space.
36
Q

Describe the Intracranial pressure (ICP) Mono-Kellie doctrine

A
  • Three components of the intracranial contents:
    • brain 1300-1500 mL
    • blood 75 mL
    • CSF 75 mL
  • Intracranial volume fixed (by skull)
  • ↑ volume of one component must be accompanied by decrease in another; if not, _ICP increases (_Monro-Kellie doctrine).
37
Q

What do we need to know about the intracranial pressure?

A
  • Measurement
  • Maintenance of normal intracranial pressure
  • Failure of compensatory mechanisms
  • Cerebral herniations
  • Systemic factors affecting intracranial pressure
38
Q

What are the compensatory mechanisms if ICP increases

A

­volume of brain tissue (e.g. tumour, haemorrhage, or brain oedema), ­CSF volume in intracranial cavity, or ­intracranial blood volume can be compensated for by the following mechanisms

  1. CSF displaced into spinal canal
  2. Cerebral veins collapse/compress
  3. Increase in CSF absorption
  4. Lumbosacral dura distensible
39
Q

What are some causes of increased intracranial pressure? (+ failure of compensatory mechanisms)

A

If there is ­volume of one or more components of intracranial cavity and compensatory mechanisms are overwhelmed, ICP rises. ICP rise may be caused by:

  • ­Volume of brain tissue by:
    • (1) space-occupying lesion (e.g. tumour, haemorrhage);
    • (2) ­Increased water content of brain (oedema).
  • ­CSF volume in intracranial cavity (hydrocephalus) by:
    • (1) Obstruction of CSF flow (obstructive hydrocephalus);
    • (2) DecreasedCSF absorption (communicating hydrocephalus);
    • (3) ­Increased CSF production by choroid plexus papilloma (rare).
  • ­Cerebral blood volume caused by:
    • (1) obstruction of cerebral venous outflow,
    • (2) loss of cerebrovascular autoregulation.
40
Q

What is the word for “­CSF volume in intracranial cavity”

A

(hydrocephalus)

41
Q

What are the Cushing’s Triad signs and mechanisms

A

Cushing’s Triad is a set of three primary signs that often indicate an increase in intracranial pressure (ICP).

Cushing’s triad:

(1) arterial hypertension;
(2) slow heart rate;
(3) slow respiratory rate.

Mechanism:

(1) reduction in blood flow to medulla;
(2) direct distortion of medulla.

42
Q

Decribe Cerebral herniations

A

If compensatory mechanisms fail to control ICP, brain tissue may be displaced:

  • From one compartment of intracranial cavity to another,
  • Or through foramen magnum into upper spinal canal.

These displacements are called cerebral herniations. Herniation of brain tissue can cause compression of part of brain and adjacent structures (cranial nerves and blood vessels), which in turn, causes secondary damage.

43
Q

What are the most important forms (3) and less common forms of cerebral herniation?

A

The most important forms of cerebral herniation are:

  1. Midline shift: displacement of one cerebral hemisphere across midline -> compress midline diencephalic structures
  2. Transtentorial herniation: herniation of medial temporal lobe through tentorial notch -> compress upper midbrain (containing reticular activating system, abnormal cause drowsiness), oculomotor nerves (dilated pupils), posterior cerebral artery.
  3. Tonsillar herniation: herniation of inferior cerebellum (cerebellar tonsils) from posterior fossa into spinal canal ® compress underlying medulla (cause Crushing’s triad).

Less common forms of herniation are:

  1. Subfalcine herniation: herniation of cingulate gyrus beneath falx cerebri;
  2. Upward herniation: herniation of superior cerebellum through tentorial notch.
44
Q

Describe the midline shift

A

Midline shift:

displacement of one cerebral hemisphere across midline -> compress midline diencephalic structures

45
Q

Describe the Transtentorial herniation

A

Transtentorial herniation:

herniation of medial temporal lobe through tentorial notch ->

  1. c_ompress upper midbrain_ (containing reticular activating system, abnormal cause drowsiness),
  2. oculomotor nerves (III) (dilated pupils),
  3. posterior cerebral artery.
46
Q

Describe the Tonsillar herniation

A

Tonsillar herniation:

herniation of inferior cerebellum (cerebellar tonsils) from posterior fossa into spinal canal -> compress underlying medulla (cause Crushing’s triad).

47
Q

Where’s the tentorial notch?

A

Transtentorial herniation: herniation of medial
temporal lobe through tentorial notch →
compression of midbrain, oculomotor nerve, posterior
cerebral artery

48
Q

Describe Cerebrovascular Autoregulation

A

Cerebral perfusion pressure (CPP) is determined by difference between mean arterial blood pressure (MAP) and i_ntracranial pressure (ICP)_:

CPP = MAP – ICP

In normal circumstances, cerebrovascular autoregulation maintains constant cerebral blood flow over a wide range of CPP (60-150mmHg). Cerebral blood vessels regulate blood supply to different parts of brain in direct response to metabolic demands for oxygen and glucose (i.e. neuronal activity).

  • Vasoactive factors released by neurons mediate constriction and dilatation of small cerebral arteries.
  • Direct innervation of cerebral blood vessels and astrocyte foot processes also may play a role in autoregulation.

If there is loss of cerebral autoregulation (e.g. cerebral infarct, tumours), _cerebral blood flow (_and cerebral blood volume) is proportional (vary passively) to arterial blood pressure. Important to maintain BP (avoid BP sudden drop) in strokes to avoid further infarct! (because cerebral blood flow will drop too)

49
Q

What is the normal Cerebral perfusion pressure?

A

CPP (60-150mmHg).

CPP = MAP – ICP

50
Q

What are the Systemic Factors that Affect Intracranial Pressure (ICP) (7)

A

Systemic Factors that Affect Intracranial Pressure (ICP)

  1. arterial blood pressure (constant ICP over normal range) But not so important because of the cerebrovascular autoregulation
  2. ↑venous pressure → ↑ICP
  3. ↑intrathoracic pressure → ↓venous return → ↑venous pressure → ↑ICP
  4. Posture: lying posture → ↑venous pressure → ↑ICP
  5. ↑PaCO2 → cerebral vasodilatation → ↑CBF → ↑ICP (greater effect)
  6. ↓PaO2 → arteriolar dilatation → ↑CBF → ↑ICP (less effect)
  7. ↑temperature (up to 42°C) → ↑CBF → ↑ICP
51
Q

Diagnose

A 28 year old man presents following a motor vehicle crash in which he was an unrestrained driver. Following a lucid interval, he is unresponsive on arrival to the ED. He has a dilated right pupil (transtentorial herniation?) and his best motor response is abnormal flexion to painful stimulus. His blood pressure starts to rise and heart rate begins to fall (Crushing’s triad due to ­ICP).

A

Extradural haematoma (acute bleeding of middle meningeal artery over the dura).- due to skull fracture

52
Q

Diagnose

A 17 year old NZ European man presents with a severe headache and a fever. He was well yesterday and played football after school. On examination he is sleepy, febrile, tachycardic and has neck stiffness (key sign of meningitis and SAH)

A
  • Meningitis until proven otherwise
  • Lumbar puncture investigation (high WBC, high protein, low/no glucose)
53
Q

Diagnose8

A 45 year old woman presents to the ED with the worst headache of her life. She was sitting at home watching the TV and the headache came ‘out of the blue’. She is now in the resuscitation room and finds the light very uncomfortable. Her blood pressure is 180/120