Cerebral Blood Flow and CNS Homeostasis Flashcards
Circle of Willis Source
- Internal Carotid
- Basilar
- Vertebral
Circle of Willis Circulation
- stratified blood flow to limit damage
- little mixing of blood from the 3 major arteries
- blockage of blood flow in Circle causes localized ischemia vs global ischemic event
Sympathetic Innervation of Cerebral Circulation
- NE and NPY released from post-ganglionic pre-synaptic terminal
- alpha 1 adrenergic receptors
- vasoconstriction and increased blood pressure
Parasympathetic Innervation of Cerebral Circulation
- ACH
- VIP and its PHM-27 pre-cursor
- vasodilation of larger blood vessels proximal to heart
Nociceptors
provide sensory innervation of distal blood vessels
Vasodilator Neurotransmitters
- substance P
- neurokinin A
- CGRP
Role of Sensory Innervation of Cerebral Circulation
- regulate sensitivity of brain vessels to painful torsion/manipulation
- reduced CSF volume = heavier brain and pain with motion
- activation of afferents causes vasodilation and increased blood flow to restore normal intracranial volume
Oxygen-Mediated Cerebral Circulation
- flow locally controlled by oxygen consumption
- more metabolically active areas = more O2 consumption and vasodilation for O2 delivery
Autoregulation
brain controls own blood flow which is held constant over range of systemic/mean arterial BP
Mean Arterial BP vs Cerebral Blood Flow
- as MABP increases, cerebral flow increases
- direct relationship until autoregulation
- when autoregulation range is exceeded, direct relationship resumes
Sympathetic Autoregulation
- range of autoregulation is extended to a higher MABP to protect capillaries from damage, esp in BBB
- vasculature will vasoconstrict to protect capillaries in brain, although systemic vascular resistance increases
Intercranial Pressure vs Cerebral Blood Flow
as intercranial pressure increases, venous outflow is obstructed and arterial flow is reduced
Effects on Systemic Blood Pressure
decreased brain perfusion activates CV control in medulla to increase systemic BP drastically ( >200) to try to force veins open for blood entry
Increased Intercranial Pressure
- hydrocephalus: increased CSF volume
- cerebral edema: swelling of brain tissue
- intracranial bleeding: blockage of CSF flow from space-occupying mass
CSF Quantities
- 150 mL in a given moment
- 500 mL / day
- no recirculation
Four Ventricles
- 2 lateral
- Third Ventricle
- Fourth Ventricle
Ventricular System
- Intraventricular Foramen: lateral to third
- Cerebral Aqueduct: third to fourth
- Median Aperture: fourth to cisterna magna
- Lateral Aperture: fourth to arachnoid space
Choroid Plexus
specialized tissue in lateral ventricles producing most CSF, remainder made by tissues lining ventricles and vessels
Passive Filtration of Serum
- first step of CSF production
- dependent on hydrostatic and oncotic pressure
- oncotic pressures cancel
- blood pressure in capillaries > tissue hydrostatic pressure
- fluid moves from vessels to ventricles
- capillary pressure dominates and pushes fluid into ventricle
Hydrostatic Pressure
- pressure in capillary > pressure in ventricle
- pressure in capillary (blood pressure) favors movement out of ventricle
- pressure around capillary (tissue hydrostatic pressure) favors movement into ventricle
Oncotic Pressure
- osmotic pressure
- depends on solute concentration
- inside capillary = pulls fluid into capillary
- surrounds fluid = pulls fluid out of capillary
- equal and opposite at choroid plexus
Modification of Ion Composition
- second step of CSF formation
- HCO3, Cl, and K concentrations controlled by channels in choroid plexus epithelia
- Aquaporin 1 permits water passage
Capillary Hydrostatic Pressure vs Intercranial Pressure
capillary hydrostatic pressure is higher than intercranial pressure would ever reach which drives CSF production
[X] CSF = [X] plasma
- Na (ranges overlap)
- HCO3
[X] CSF > [X] plasma
- Mg: interacts with Ca, added by choroid plexus
- Cl: added by choroid plexus
- CO2: from neuronal metabolism
[X] CSF < [X] plasma
- K: tightly controlled bc changes potential
- Ca: tightly controlled because toxic in high quantities
- Protein
- Glucose: fuel for neurons
CSF Flow
-via ventricular system unidirectionally
-reabsorbed by arachnoid villi
-bulk flow into venous sinuses driven by pressure inside villi
returns to general circulation
CSF Absorption vs Intracranial Pressure
- CSF absorption proportional to intracranial pressure
- no absorption at 68 mm CSF
- normal pressure at 112 mm CSF
- pressure of CSF drives movement into sinuses
- body prevents reabsorption of CSF at low pressures bc movement is not driven
CSF Role
- brain protection and “floatation”
- reduces weight of lipid/myelin rich brain so brain is not subject to motion/shock
Limited Exchange Mechanisms of BBB Capillaries
- tight junctions between endothelial cells
- glial endfeet
Glial Endfeet
- close contact with blood vessels
- cover capillaries
- increase distance over which substance diffuses from blood to CSF to reduce diffusion
Chemical Mechanisms of BBB
lipophilic bilayer membranes to prevent passage of hydrophilic materials in blood
Passive Diffusion of Substances Across BBB
- H2O: via AQP4
- CO2: moves from CSF to capillary for removal
- O2: leave capillaries to neurons
- free steroid hormones
Glut-1 Transporter
- non-insulin dependent transporter of glucose across BBB
- larger transporter on capillaries vs astroglia
Glut-3 Transporter
non-insulin dependent transporter to move glucose into neurons
Na/K/2Cl Transporter
- electroneutral movement of ions from CSF to blood unidirectionally to keep K in CSF low
- expression regulated by endothelin 1 and 2
P-Glycoprotein/MDR-1
- transports drugs that cross BBB back into blood
- binds wide variety of substances with diff structures
Circumventricular Organs
- neural tissue not protected by BBB due to capillaries lacking tight junctions
- Four: Posterior Pituitary, Area Postrema, Organum Vasculosum of Lamina Terminalis, and subfornical organ
Circumventricular Organs: Posterior Pituitary
exposure to plasma blood for hormone release and control
Circumventricular Organs: Area Postrema
- cluster of neurons at surface of brain where fourth ventricle opens
- triggers vomiting in response to chemical detection
Circumventricular Organs: Organum Vasculosum of Lamina Terminalis and Subfornical Organ
control water/thirst/blood volume to regulate blood osmolarity
