Lecture 34: CSF

Question 1

What are the 2 ‘spaces’ between the meninges?

Answer 1

• 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).

Question 2

What are the two ‘types’ of meninges?

Answer 2

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.

Question 3

What is CBF?

Answer 3

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

Question 4

Where is the CSF produced?

Answer 4

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).

Question 5

Describe the Choroid Plexus Structure

Answer 5

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

Question 6

Total CSF volume is usually _______\_

The CSF volume in ventricles is __________\_

Answer 6

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.

Question 7

Describe how CSF are produced

Answer 7

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

Question 8

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

Answer 8

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.

Question 9

Describe the direction of flow of the CSF

Answer 9

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).

Question 10

Describe where/how the CSF are absorbed

Answer 10

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.

Question 11

Label 1 and 5

Answer 11

1) Third ventricle
5) Posterior horn of lateral ventricles

Question 12

What is the turnover rate of CsF

Answer 12

3-4x per day

(600ml/day 0.35ml/min)

Question 13

Most of the CSF is in the….

Answer 13

Subarachnoid space

Question 14

What are Arachnoid villi?

Answer 14

• 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

Question 15

CSF absorption is proportional to ___________\_

Answer 15

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.

Question 16

How can a sample of CSF be obtained?

Answer 16

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.

Question 17

Which lumbar space do you obtain the CSF from?

Answer 17

L3/4 intervertebral space

Question 18

What is the normal CSF composition (KNOW THE NUMBERS)

Answer 18

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)

Question 19

How much glucose should there be in CSF?

Answer 19

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

Question 20

How much WBC should be in the CSF?

Answer 20

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

Question 21

How much protein is there in the CSF?

Answer 21

Protein <0.45g/l

Question 22

How does the CSF change in Meningitis?

Answer 22

• ↑ 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)

Question 23

How does the CSF change in Subarachnoid Haemorrahge?

Answer 23

• ↑ 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)

Question 24

CSF has…

↑ white blood cells (mostly polymorphs)

↑ protein

± ↓ glucose

What do they have?

Answer 24

Meningitis

Question 25

CSF shows.. ↑ red blood cells “xanthochromia” (yellow discolouration due to red cell breakdown products) What does this person have?

Answer 25

Subarachnoid haemorrhage

Question 26

What are the functions of CSF?

Answer 26

* _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)

Question 27

What are the functions of the Blood-brain barrier?

Answer 27

**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

Question 28

What does the Blood Brain Barrier consist of?

Answer 28

* specialised endothelial cells * thick basement membranes * astrocytic processes on capillaries

Question 29

Compare the systemic and brain capillaries

Answer 29

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.

Question 30

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

Answer 30

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**

Question 31

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

Answer 31

* _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).

Question 32

What are the 5 ways the BBB can be disrupted?

Answer 32

BBB can be disrupted in several ways: 1. _Disruption of **tight junctions**_, leading to passage of molecules between cells. 2. _Disruption (proteolysis) of **basement membrane**s_, e.g. inflammatory response in meningitis can cause BBB breakdown, so white cells and protein appear in CSF. 3. _Disruption of endothelial cell-a**strocyte 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!).*

Question 33

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

Answer 33

* 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

Question 34

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

Answer 34

**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.

Question 35

Normal CSF pressure (in adults) is _\_\_\_\_\_\_\_\_\_\_\__

Answer 35

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.

Question 36

Describe the Intracranial pressure (ICP) Mono-Kellie doctrine

Answer 36

* _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).

Question 37

What do we need to know about the intracranial pressure?

Answer 37

* Measurement * Maintenance of normal intracranial pressure * Failure of compensatory mechanisms * Cerebral herniations * Systemic factors affecting intracranial pressure

Question 38

What are the compensatory mechanisms if ICP increases

Answer 38

­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

Question 39

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

Answer 39

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 volum**e caused by: * (1) obstruction of cerebral venous outflow, * (2) loss of cerebrovascular autoregulation.

Question 40

What is the word for "­CSF volume in intracranial cavity"

Answer 40

(hydrocephalus)

Question 41

What are the Cushing's Triad signs and mechanisms

Answer 41

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.

Question 42

Decribe Cerebral herniations

Answer 42

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.

Question 43

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

Answer 43

**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_.

Question 44

Describe the midline shift

Answer 44

**_Midline shift:_** displacement of _one cerebral hemisphere across midline_ -\> compress _midline diencephalic structures_

Question 45

Describe the **_Transtentorial herniation_**

Answer 45

**_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._

Question 46

Describe the Tonsillar herniation

Answer 46

**_Tonsillar herniation:_** herniation of _inferior cerebellum_ (cerebellar tonsils) from posterior fossa into spinal canal -\> _compress underlying medulla_ (cause _Crushing’s triad)_.

Question 47

Where's the tentorial notch?

Answer 47

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

Question 48

Describe Cerebrovascular Autoregulation

Answer 48

**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)*

Question 49

What is the normal Cerebral perfusion pressure?

Answer 49

CPP (60-150mmHg). CPP = MAP – ICP

Question 50

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

Answer 50

**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. **↑P_aCO₂** → cerebral vasodilatation → ↑CBF → ↑ICP (greater effect) 6. **↓P_aO₂** → arteriolar dilatation → ↑CBF → ↑ICP (less effect) 7. **↑temperature** (up to 42°C) → ↑CBF → ↑ICP

Question 51

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).

Answer 51

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

Question 52

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)_

Answer 52

* Meningitis until proven otherwise * Lumbar puncture investigation (high WBC, high protein, low/no glucose)

Question 53

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

Answer 53

* [Subarachnoid haemorrhage](https://www.coursebuilder.cad.auckland.ac.nz/flexicourses/1884/publish/1/8_1.html)