INCREASED INTRACRANIAL PRESSURE, BLOOD BRAIN BARRIER, AND MENINGEAL IRRITATION

Contents of the Skull

Cerebrospinal Fluid (CSF)

Blood

Brain

CSF color?

Clear, colorless (water-like)

CSF cellular or acellular?

Acellular (0-5 lymphocytes normal)

No substances in CSF not found in ____

No substances in CSF not found in blood 

CSF vs PLASMA

• CSF has higher concentrations of?

• Lower concentrations of?

CSF vs PLASMA

• sodium, chloride, and magnesium 

• potassium, calcium, and glucose, and protein 

Functions of CSF (Skim)

• Cushions and protects CNS 

• Provides mechanical buoyancy and support 

• Reservoir and assist in regulation of contents of skull 

• Nourishes CNS 

• Removes metabolites (CO2, lactate, hydrogen ions) 

• Pathway for pineal gland secretions to reach pituitary gland

State CSF:

• Appearance

• Volume

• Rate of Production

State CSF:

• Appearance : Clear, colorless

• Volume: 150 ml

• Rate of Production: 0.35mL/min

State CSF: (if pabibo ka)

• Pressure (Spinal tap in lateral recumbent position)

• Protein

• Glucose

• “ Chloride

• Cells

State CSF: (if pabibo ka)

• Pressure (Spinal tap in lateral recumbent position) : 60-150mm H2O

• Protein: 15-45 mg/100ml

• Glucose : 0-85 mg/100ml 

  60% of plasma glucose

• Chloride: 720-750 mg/100ml

• Cells: 0-3 or 5 lymphocytes per cubic mm

Average Intracranial Volume

1,700 mL 

Brain Volume

1,200-1,400 mL

CSF Volume

70-160 mL (25 mL in ventricles) 

Blood Volume

150 mL

Average Rate of Formation

21-22 mL/h (0.35 mL/min; 500mL/day)

Bulk volume of CSF is renewed how many times per day?

4-5x/day 

70% of the CSF is formed in the _________ of the ventricles

Choroid plexus

18% of the CSF is formed by?

capillary ultrafiltrate

12% of the CSF is formed by?

metabolic water production based on glucose oxidation 

Villous structures extending  from ventricular surface into CSF

Regulates production and composition of CSF

Choroid Plexus

Part of the choroid plexus that is intact with the CSF

Apical microvilli

___________ surround apical regions of epithelial cells form a barrier to the passive exchange of proteins and hydrophilic solutes between blood and CSF 

Tight junctions

Pressure is highest in the ______ and diminishes successively along the way 

ventricles

what helps the choroid plexus drive fluid centrifugally from ventricles

Arterial pulsations

Passively returned to venous system via?

Arachnoid villi

Arachnoid villa is most numerous in the?

superior sagittal sinus

Sum of volumes of brain, CSF, and intracranial blood is constant, as per what doctrine?

Monroe Kelly Doctrine

_________ stage:
Small increments in brain volume does not immediately raise ICP because of buffering effect of displacement of CSF from the cranial cavity into spinal canal 

To a lesser extent, there is deformation of brain and stretching of falx cerebri and tentorium

Compensated Stage

Symptoms of the compensated phase of increased intracranial pressure:

• headache

• vomiting

• papilledema

  
  

__________ stage:
Mass within one dural compartment leads to displacement or herniation of brain tissue

Decompensated Stage

Increased intracranial pressure during the decompensated stage can cause:

• Reduced volume of intracranial blood in veins and sinuses 

• Slower formation of CSF

Symptoms of the decompensated stage?

• deterioration of consciousness

• Cushing’s triad 

What is the Cushing’s triad

• HTN

• Bradycardia

• Irregular respiration

Causes of Increased ICP (skim):

• Cerebral or extracerebral mass 

  • brain tumor, abscess, hematomas, cerebral infarction with edema

• Generalized brain swelling

  • Hypoxic Ischemic Encephalopathy (HIE), hypertensive encephalopathy

• Increased venous pressure

  • cerebral venous thrombosis, obstruction in jugular veins

• Obstruction to flow and absorption of CSF 

• CSF volume expansion or increased CSF production

  
  

  
  

General symptoms of increased intracerebral pressure (skim)

• Papilledema → swelling of optic disc

• Diplopia with internal squint (lateral rectus palsy secondary to abducens nerve lesion)

• Decreased level of consciousness 

• Bulging fontanel, separation of sutures, rapidly enlarging head (in babies)

Abnormal mass of tissue from excessive, uncontrollable cell division; benign or malignant

Tumors

Localized collection of pus

Abscess

Sac-like pocket of membranous tissue which contains fluid, hair, or other substances

Cysts

Localized collection of blood

Hematoma

Chronic inflammatory lesion characterized by large number of various cell types (macrophages, lymphocytes, fibroblasts, giant cells), some degrading and some repairing tissues 

• I.e. tuberculosis

Granulomas

• Increase in MAP ______ CBF 

• Increase in ICP _______ CBF

• Increase in MAP increases CBF 

• Increase in ICP decreases CBF

2 types of brain barriers:

• Blood-CSF barrier

• Blood brain barrier (BBB)

Selective semipermeable membrane between blood and interstitium of brain, allowing cerebral vessels to regulate molecule and ion movement between blood and brain

Separates CSF and brain from blood

Blood Brain Barrier

Functions of the BBB (skim)

• Maintain homeostatic environment within CNS structures 

• Shield brain from toxic substances 

• Supply brain within nutrients

Lebron big veiny dih to yo crack, name the continuous homogeneous basement membrane that together with the astrocytic processes, separate plasma from the extracellular space within CNS 

Capillary Endothelium but slide it in anyway twin

Capillary endothelium contains_________ which restrict intracellular diffusion of solutes

Tight junctions

True or false:

The size of the molecule is inversely proportionate to its permeability

Yes king

True or false:

The lipid solubility of the molecule is inversely proportionate to its permeability

No king, its directly proportionate

• Gasses and water are _____ permeable 

• Glucose and electrolytes pass more ______

• Almost _________ to plasma proteins and other large, organic molecules 

• Compounds with ________ remain within the circulatory system

• Gasses and water are readily permeable 

• Glucose and electrolytes pass more slowly 

• Almost impermeable to plasma proteins and other large, organic molecules 

• Compounds with MW ≥ 60,000 remain within the circulatory system

Movement of Molecules : Water

Diffusion

Movement of Molecules: extracellular potassium from brain and CSF to plasma against concentration gradient

Active transport (NaK ATPase)

Movement of Molecules :  D-glucose, large amino acids 

Carrier-mediated transport

Lipid soluble molecules bound to ______ do not permeate

protein

Lebron dih to yo crack, what does Dopa Decarboxylase break down to form serotonin?

Just slide that shi in gng

5-hydroxytryptophan

Dopa Decarboxylase breaks down dopamine to form?

L Dopa

Specialized tissues located at strategic positions in the midline ventricular system that are devoid of BBB

Circumventricular Organs (CVOs)

Circumventricular Organs have ________ capillary endotheliums

fenestrated

All CVOs except ________ are unpaired and bear relationship with the _______ and ________

All CVOs except area postrema are unpaired and bear relationship with the diencephalon and 3rd ventricle 

CVO that secretes melatonin

Pineal Body

CVO that regulates water intake

Subfornical Organ

Circulating _________ acts in subfornical organ to increase water intake

angiotensin II

CVO that is also known as the supraoptic crest 

controls vasopressin secretion and thirst

Organum Vasculosum of Lamina Terminalis 

CVO also known as the posterior pituitary gland

Secretes hormones into the blood

Neurohypophysis

CVO located at the medulla

Area postrema

Ventricular enlargement due to obstruction to normal CSF flow

Hydrocephalus

Types of Hydrocephalus:

Overproduction of CSF 

Inadequate absorption

Communicating or Non-obstructive

Types of Hydrocephalus:

Obstruction of CSF flow

Non- communicating or Obstructive

Accumulation of CSF and expansion of ventricles are _________

unidirectional

• Proximal to obstruction ________

• Ventricle _______ to obstruction enlarges the most 

• Proximal to obstruction enlarges

• Ventricle closest to obstruction enlarges the most 

Swelling of brain due to abnormal shifts of water across various comparts

Cerebral Edema

Most common cerebral edema due to disruption of the BBB

Extracellular edema which mainly affects white matter via leakage from capillaries 

Vasogenic Edema

Causes of vasogenic edema:

• Peritumor edema 

• Cerebral abscess 

• Cerebral hemorrhage

Edema that results from the inability to maintain Na-K ATPase pumps which is responsible for high extracellular and low intracellular sodium concentration

Cytotoxic Edema 

In cytotoxic edema there is cellular swelling and a decrease in _____ volume

ECF volume

True or false:
In cytotoxic edema, there is no endothelial dysfunction and does not affect capillary permeability

True

Cytotoxic edema affects which matter of the brain?

Affects gray and white matter

Causes of cytotoxic edema:

• Traumatic brain injury

• Stroke

Results from derangements of osmolarity 

Brain cells pull water from the plasma 

Widespread edema

Osmotic Edema

Causes of Osmotic edema:

• Hyponatremia 

• Diabetic ketoacidosis

Results from outflow of CSF from intraventricular space to the interstitial areas of brain

Interstitial (Hydrocephalic) Edema

In interstitial edema, there is increased pressure in the _________

ventricle

In interstitial edema:
Fluid accumulates in the extracellular space of the ________

Disruption of ___________ lining

• White matter

• ventricular ependymal lining

Interstitial edema is caused by:

• Hydrocephalus

• Meningitis

Pressure from a mass within any one dural compartment causes shifts of herniations of brain tissue to an adjacent compartment with lower pressure (tissue is displaced)

Herniation

Most common brain herniation

Cingulate gyrus is pushed under the falx

Subfalcial (Cingulate/ Subfalcine) Herniation

Subfalcial (Cingulate/ Subfalcine) Herniation is caused by?

Generally caused by unilateral frontal, parietal or temporal lobe disease

Subfalcial herniation causes occlusion of the ________ resulting to a ______ infarct

• ACA

• frontal lobe infarct

Downward displacement of the inferomedial parts of the cerebellar hemisphere (tonsil) through the foramen magnum, dorsolateral to cervical cord 

Preterminal even as brainstem is compressed to clivus

Cerebellar- Foramen Magnum Herniation

Cerebellar- Foramen Magnum Herniation leads to:

respiratory arrest 

In cerebellar-foramen magnum herniation there is an inferior descent of the cerebellar tonsils ______ below the foramen magnum level

>3mm

The line at the level of the foramen magnum is also know as?

McRae line

Superior cerebellar vermis and midbrain are pushed upward compressing the dorsal mesencephalon, adjacent blood vessels and cerebral aqueduct 

Through incisura of the tentorium 

Upward Cerebellar Herniation

Upward cerebellar herniation is caused by?

mass effect in the posterior fossa

Upward cerebellar herniation can cause?

Decerebrate posturing

Downward transtentorial 

Symmetric or severe mass effect resulting in the downward displacement of the thalami and midbrain

Central Transtentorial Herniation

Transtentorial downward 

When expanding lesion forces the medial edge of the temporal lobe to herniate medially and downward over the free tentorial edge into the tentorial notch

Uncal Herniation

Key signs of uncal herniation:

• Ipsilateral fixed, dilated pupil due to ______ compression with or without problems with _____ mobility

• Loss of consciousness due to distortion of _________

• Contralateral hemiparesis due to compression of ________

• Compression of the _____ causing (B) visual field infarction

Key signs of uncal herniation:

• Ipsilateral fixed, dilated pupil due to CNIII compression with or without problems with ocular mobility

• Loss of consciousness due to distortion of ARAS (Ascending reticular activation system)

• Contralateral hemiparesis due to compression of cerebral peduncles

• Compression of the PCA causing (B) visual field infarction

Herniation of brain external to the calvaria through a skull defect 

Herniated tissue is at risk of ischemia and venous infarction

Extracranial or Transcalvarial Herniation

causes of Extracranial or Transcalvarial Herniation

• Trauma

• Post surgical (craniectomy)