What is the effect of an increase in CO2 on the brain?
an increase in carbon dioxide concentration in the arterial blood perfusing the brain greatly increases cerebral blood flow
• A 70% increase in arterial P CO2 approximately doubles cerebral blood flow
• CO2 increase cerebral blood flow by combining first with water in the body fluids to form carbonic acid and leads to dissociation of the acid to form H+ ions
o CO2 has an indirect way of increasing cerebral blood flow by making H+ in the blood
What is the effect of an increase in H+ on the brain?
- Dilation is almost directly proportional to the increase in hydrogen ion concentration up to a blood flow limit of about twice normal
- H+ ions are bad because increased concentrations greatly depress neuronal activity
- The body’s mechanism for removal of excess H+ is to increase blood flow which will carry away the excess CO2 which removes carbonic acid from the tissues and this reduces the H+ concentration towards normal
- Used to keep a constant H+ concentration in cerebral fluid and keep a normal level of neuronal activity
What is the effect of an decrease in O2 on the brain?
- If the blood flow to the brain ever becomes insufficient there is immediate vasodilation to return blood and transport of oxygen to cerebral tissues to near normal levels
- Decreases in cerebral tissue PO2 below about 30mmHg (norm 35-40) immediately causes vasodilation and increase if cerebral blood flow
- Important b/c at PO2 levels below 20 the brain becomes deranged and can even cause coma
- Pretty much the brain is touchy when it comes to oxygen levels and only a slight decrease will cause an increase in blood flow
What are teh effects of arterial BP on the brain?
during normal daily activities arterial blood pressure can fluctuate wildly rising to high levels during states of excitement (orgasm) or strenuous activity and falling to low levels during sleep
• Cerebral blood flow is autoregulated extremely well between pressure limits of 60 and 140 mmHg
o Means the arterial pressure can get as low as 60 or as high as 140 without significant changes in cerebral blood flow
• Even in people with hypertension autoreguation still happens with blood pressure between 160 and 180 mmHg
What happens to the blood flow to the brain if the sympathetic system is lesioned?
• Transection of sympathetic nerves or stimulation to them doesn’t effect blood flow to the brain b/c blood flow autoregualtion can override there effects
• When mean arterial pressure rises acutely to an exceptionally high level like during exercise or sex sympathetics are used to constrict the large and intermediate sized brain arteries enough to prevent the high pressure from the smaller brain blood vessels
o Important in preventing vascular hemorrhages into the brain-cerebral strokes
What are the roles of astrocytes?
close coupling between neuronal activity and cerebral blood flow is due in part to substances released by astrocytes which surround blood vessels of the central nervous system
• Are star shaped non neuronal cells that support and protect neurons as well as provide nutrition
• Have numerous projections that make contact with neurons and the surrounding blood vessels providing potential mechanism for nerurovascular communication
• Gray matter astrocytes (protoplasmic astrocytes) extend fine processes that cover most synapses and large foot processes that are closely apposed to the vascular wall
Astrocytes help regulate which ion?
• Electrical stimulation of excitatory glutaminergic neurons leads to increases in intracellular calcium ion concentration in astrocyte foot processes and vasodilation of nearby arterioles
o Stimulation of adjacent excitatory neuron which causes the astrocytes to release a chemical which causes local vasodilation
How does the choroid plexus make CSF?
- The plexus projects into the temporal horn of each lateral ventricle, the posterior portion of the 3rd ventricle and the roof of the 4th ventricle
- Secretion of fluid into the ventricles by the choroid plexus depends on active transport of sodium ions through the epithelial cells lining the outside of the plexus
- The sodium ions in turn pull along large amounts of chloride ions as well b/c of the positive charge of the sodium ion attracts the chloride ions negative charge
- The two ions combined increase the quantity of osmotically active sodium chloride in the CSF which then causes almost immediate osmosis of water through the membrane and this provides the fluid for secretion
- Also glucose is moved into the CSF while potassium and bicarbonate ions are moved out of CSF into capillaries
- This results in CSF having osmotic pressure and sodium ion concentration equal to that of plasma
How do arachnoid vili reabsorb CSF?
- Arachnodial villi are microscopic fingerlike inward projections of the arachnodial membrane through the walls and into the venous sinuses
- A bunch of these villi will form macroscopic structures called arachnodial granulations that can be seen protruding into the sinuses
- Endothelial cells covering the villi have been shown to have vesicular passages directly through the bodies of the cells large enough to allow relatively free flow of CSF, dissolved protein molecules, even large particles as large as red and white blood cells into the venous blood
How is CSF pressure regulated?
- The arachnoidal villi function like valves that allow CSF and its contents to flow readily into the blood of the venous sinuses while not allowing blood to flow backwards in the opposite direction
- Normally the valve action of the villi allows CSF to begin to flow into the blood when CSF is about 1.5 mmHg greater than the pressure of the blood in venous sinuses
- If CSF fluid pressure raises still higher the valves just open wider
- In diseased states the villi sometimes become blocked by large particulate matter, by fibrosis, or by excess of blood cells that have leaked into the CSF
What are the Sx of pappiledema when CSF pressure in increased?
• When CSF system pressure increases it also increases inside the optic nerve sheath
o This pushes fluid first into the optic nerve sheath and then along the spaces between the optic nerve fibers to the interior of the eyeball
o The high pressure decreases outward fluid flow in the optic nerves causing accumulation of excess fluid in the optic disc at the center of the retina
o The pressure in the sheath also impedes flow of blood in the retinal vein thereby increasing the retinal capillary pressure throughout the eye which results in more retinal edema
• Tissues of the optic disc are much more distensible than those of the remainder of the retina so the disc becomes far more edematous than the remainder of the retina and swells into the cavity of the eye
• Swelling of the optic disc can be observed with ophthalmoscope and is called papilledema
What is the fxn of the BBB?
• Blood brain barrier has specific carrier molecules that facilitate transport of hormones such a leptin to specific receptors that control functions such as appetite and sympathetic nervous system activity
• Blood brain barrier is highly permeable to water, carbon dioxide, oxygen, and most lipid soluble substance such as alcohol and anesthetics
• Slightly permeable to electrolytes like sodium, chloride, and potassium
• Totally impermeable to plasma proteins and non-lipid soluble large organic molecules
o Makes it impossible to achieve effective concentrations of these drugs in the brain
• The cause of the low permeability of the blood brain barriers is the manner of the endothelial cells of the brain tissue capillaries are joined to each other
• Joined by tight junctions- the membrane of the adjacent endothelial cells are tightly fused rather than having large slit pores between them as is the case for most capillaries in the body
Sx of brain edema?
• One the most serious complications of abnormal cerebral fluid dynamics
o b/c the brain is encased in the cranial vault accumulation of extra edema fluid compresses the blood vessels often causing seriously decreased blood flow and destruction of brain tissue
• Usual cause of brain edema is either greatly increased capillary pressure or damage to the capillary that makes the wall leaky to fluid
o Common cause is a serious blow to the head leading to brain contusion in which the brain tissues and capillaries are traumatized and capillary fluid leaks into the traumatized tissues
What are the 2 viscious circles to cause braine edema?
- Edema compresses the vasculature and this in turn decreases blood flow and causes brain ischemia. The ischemia in turn causes artery dilation with still further increases capillary pressure. The increase in pressure then causes more edema fluid so the edema become progressively worse
- The decreased cerebral blood flow also decreases oxygen delivery. This increases the permeability of the capillaries allowing still more fluid leakage. It also turns off the sodium pumps of the neuronal tissue cells thus allowing these cells to swell in addition
Tx of brain edema?
o One is to infuse intravenously a concentrated osmotic substance such as mannitol which pulls fluid by osmosis from the brain tissue
o Also can do a ventricular needle puncture of the lateral ventricles
What is the relationship between O2 use and brain metabolism?
- Brain is not capable of anaerobic metabolism meaning it cannot be without oxygen for very long at all
- The high metabolic rate of the neurons depends on second to second delivery of oxygen from the blood
- Sudden cessation of blood flow to the brain or sudden total lack of oxygen in the blood can cause unconsciousness within 5 to 10 seconds
What is the relationship between glucose use and brain metabolism?
- Under normal conditions almost all the energy used by the brain cells is supplied by glucose derived from the blood
- Delivered by minute and second to second from the capillary blood
- Only about a 2 minute supply of glucose normally stored as glycogen in the neruons at a time
- Glucose delivery to neurons is NOT dependent on insulin
What if the pt is hyperglycemic?
- Patients with serious diabetes with essential zero insulin glucose can still diffuse readily into the neurons
- This is most fortunate in preventing loss of mental function in diabetic patients
What if the pt is hypoglycemic?
- Over treated with insulin the blood glucose concentration falls extremely low b/c glucose it taken up into all the cells
- When this happens there isn’t enough glucose left in the blood to supply the neurons properly and mental function becomes seriously deranged leading to coma and even more often mental imbalances and psychotic episodes
