03-25 CBF and BBB

Question 1

OBJECTIVE: Locate the anatomical substrate for the BBB and describe its significance

Answer 1

The BBB is formed by the endothelium of cerebral capillaries that specialize when induced to do so by astroglia. It is important for maintaining a highly regulated aqeous environment for the neurons.

Question 2

OBJECTIVE: List the features of a substance that would promote its ability to cross the BBB

Answer 2

Substance that pass through the BBB easily are:

• small
• non-polar
• not protein-bound
• lipid soluble

Question 3

OBJECTIVE: List the areas of the brain without a blood-brain barrier and discuss the rationale for these areas to lack such a barrier.

Answer 3

Areas without a BBB include those for sensing blood conditions (e.g. subfornical organ and the area postream of the brain stem which controls vomiting) and those involved in hormone level sensing and release (e.g. infundibulum of the hypothalamus and anterior pituitary)

Question 4

OBJECTIVE: Describe how the areas of the brain without a BBB are isolated from those having such a barrier.

Answer 4

specialized glial cells call tanicytes separate these areas from the rest of the brain

Question 5

OBJECTIVE: Locate the blood-CSF barrier. Discuss the process of substances crossing the barrier.

Answer 5

The blood CSF barrier is located at the level of the epithelium in the choroid plexus. Substances that want to pass from the blood to the CSF can only do so through specialized transporters, many of whom couple nutrient transport with transport of ions down their concentration gradient.

Question 6

OBJECTIVE: Compare and contrast the concentration of ions and molecules in the CSF with that of the blood.

Answer 6

He stressed the bolded ones.

• SAME: Osmolarity, Na+ same
• CSF has more:
  
  • water (99% vs. 93%)
  • Cl- (119mEq/L vs. 102)
• CSF has more:
  
  • protein BIG TIME (35 mg/dL vs. 7000 mg/dL)
  • glucose (~60 mg/dL)
  • Ca2+ (2.1 vs. 4.8 mEq/L)
  • Mg2+ (0.3 vs. 1.7 mEq/L)
  • K+ (2.8 vs. 4.5 mEq/L)
  • H+ (pH = 7.3 vs. 7.41)

Question 7

VOCAB: autoregulation

Answer 7

ability of the brain to maintain a constant internal blood pressure regardless of the MAP

• map possible by myoepithelia cells in the precapillary arterioles which constrict in response to stretch
• has limits: MAP of 70-160 mmHg
  
  • this range can be reset in the setting of chronic HTN

Question 8

VOCAB: Blood-brain barrier

Answer 8

specialized epithelium in brain capillaries that have:

• no fenestrations
• tight junctions between cells
• few pinocytotic vesicles
• high metab. activity due to increased active transport

Question 9

VOCAB: Blood-CSF barrier

Answer 9

made possible by the epithelium of the choroid plexus (i.e. not the capillaries running through the choroid plexus which are fenestrated, etc.); have tight junctions, few pinocytotic vesicles and lots of active transporters

Question 10

STUDY Q?: Why is acute hypotension potentially more dagerous in patients with chronic HTN?

Answer 10

Because the auto-regulation can be re-set to this higher MAP maximums meaning autoregulation will now fail at a higher minimum (the whole range that autoregulation works shifts to the right)

Question 11

STUDY Q?: Why was hyperventilation utilized acutely in pts w/ severe head trauma and increased ICP? Why is this practice potentially harmful?

Answer 11

Because low CO₂ levels cause vasoconstriction and decrease ICP. This can happen to such an extent, however, that resistance to CBF is increased to the point of causing ischemia.

Question 12

STUDY Q?: Why do tumors enchance with contrast administration? What causes the edema surrounding malignant brain tumors?

Answer 12

Tumors enhance with contrast administration because they originate outside of the BBB or they have compromised the BBB.

Edema surrounding malignant tumors is likely due to vasoactive and endothelial-destroying substances secreted by the tumors (per Wikipedia)

Question 13

STUDY Q?: Why does choroid plexus enchance on imaging studies after IV contrast administration?

Answer 13

Because the choroid plexus has normal capillaries (i.e. is outside of the BBB)

Question 14

STUDY Q?: How could you get good brain concentration of chemotherapeutic agents that do not cross the BBB?

Answer 14

• Inject directly into the CSF
  
  • LP, ventricular catheter
• Use Intra-arterial osmotic agents or other vasoactive agents to temporarily open the BBB
  
  • (e.g. mannitol, adenosine, leukotrienes, interstitial radiation)
• take advantage of pathological weakening of BBB?
  
  • Penicillin in bacterial meningitis, e.g. (on slide)

Question 15

STUDY Q?: What would it tell you if an area of the brain showed accumulation of IV-injected contrast on a CT scan or MRI?

Answer 15

That would show that such an area is outside the confines of the BBB.

Question 16

What is the Monro-Kellie doctrine?

Answer 16

Brain is box with finite volume

volume = CSF + brain tissue + blood volume

brain swelling, masses, bleeding also take up space

Question 17

What is Cushing’s reflex?

Answer 17

Increased ICP presents as:

• Increased BP
• Decreased HR

Question 18

Is metabolic actiivity higher in grey or white matter?

Answer 18

Twice as high in grey matter than white matter.

Question 19

How does CSF flow?

Answer 19

lateral ventricles -> foramen of Monroe -> 3rd ventricle -> cerebral aqueduct -> 4th ventricle -> surrounding of brain and spinal cord

reabsorbed by arachnoid granulations