1: Blood-Brain Barrier and Formation of CSF Flashcards
Describe factors involved in regulation of regional blood flow. (4 main factors, also define sub-factors)
Gray matter requires tons of blood
Fluctuates little with the cardiac cycle
- **Autoregulation: maintains CBF at constant rate despite variations in MAP
- Low arterial pressures -> dilate, high arterial pressures -> constrict
- Occurs via a myogenic reflex
- Set higher with chronic hypertension - Chemical mechanisms: (2)
- CO2 reactivity: increased CO2 -> vasodilation, decreased CO2 -> vasoconstriction
- Metabolic coupling: CBF is directly correlated to metabolism via local vasoactive metabolites (adenosine, PG, glutamate, NO, etc) - Neuronal control: sympathetic and sensory input
- Blood viscosity: severe dehydration, Hct, RBC aggregation/flexibility, plasma protein concentrations, etc
Locate the anatomical substrate for the blood-brain barrier and describe its significance.
Significance: essential for… (3)
- Regulating movement of substances into/out of brain
- Maintaining homeostatic environment
- Maintaining constant intracranial pressure
Substrate: CNS capillary endothelial cells (5 features)
- Tight junctions between cells
- Few pinocytotic vesicles
- Tons of mitochondria
- CNS vessel-specific enzymes
- *Induced by astrocytic foot processes
List the features of a substance that would promote its ability to cross the blood brain barrier. (6 features)
MOST IMPORTANT: is there a transport system?
Permeability increased by… (5)
- Lipophilicity
- Decreased size
- Decreased polarity
- Decreased charge
- Decreased binding of serum proteins
Define the difference between facilitated diffusion and active transport.
Facilitated diffusion: driven by concentration gradients set up by ion pumps
-Most BBB transport mechanisms are facilitated diffusion
Active transport: driven by use of ATP
List brain regions lacking a blood-brain barrier and discuss the significance of this. (3)
All need direct access to blood stream!
Subfornical organ: detects and regulates osmolarity
Area postrema of brainstem: samples blood, elicits autonomic and vomiting responses
Median eminence: main site of release of hormone inhibiting/releasing factors to anterior pituitary
Locate the blood-CSF barrier and discuss the process of substances crossing this barrier.
No brain-CSF barrier exists
Blood-CSF barrier made of specialized choroid plexus epithelial cells surrounding the choroid plexus capillaries
- Cuboidal
- Microvilli on CSF side
- Tight junctions between cells
- Lots of mitochondria
-> Have many of the same transport mechanisms/requirements as BBB
Compare and contrast the concentration of ions are molecules in the CSF with that of the blood. (5 differences)
CSF has:
- Very little protein (none crosses CP epithelial cells)
- At least 2/3 normal glucose
- Very low K, Ca, Mg
What is the Monro-Kellie doctrine?
Intracranial volume is fixed and equal to brain volume + CSF + blood volume
Any increase in volume of any of the contents in the head will increase intracranial pressure
Define perfusion pressure.
The pressure pushing blood through the brain
Equals MAP minus intracranial pressure
What is the Cushing response?
Markedly elevated blood pressure due to increased intracranial pressure, accompanied by slow HR
Body trying to push blood through the brain
What prevents compounds entering brain regions lacking a blood-brain barrier from diffusing into the rest of the brain/spinal cord?
Tanicytes: specialized glial cells that surround the regions lacking a BBB, preventing diffusion
Describe the course of CSF circulation from the choroid plexus to reabsorption.
Lateral ventricles
- > Intraventricular foramen of Monroe
- > Third ventricle
- > Cerebral aqueduct
- > 4th ventricle
- > Foramina of Luschka and Magendie
- > Subarachnoid space (baths outside of brain and spinal cord)
- > Arachnoid granulations
- > Venous sinuses
What are the arachnoid granulations? How do they perform their function?
Mushrooms of the arachnoid mater that project into sinuses, reabsorb CSF
Form temporary openings that allow bulk transport of CSF into surrounding venous blood
