CM100 Integrated Basic Sciences Physiology PDF

CM100: Integrated Basic Sciences PHYSIOLOGY: The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism Dr. Rolan Lyndon Osi...

CM100: Integrated Basic Sciences PHYSIOLOGY: The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism Dr. Rolan Lyndon Osial, MD, FPNA | September 11, 2024 1:30pm - 4:00pm TOPICS A. Learning Objectives The Autonomic Nervous System B. The Autonomic Nervous System General Organization of the Autonomic General Organization of the Autonomic Nervous System Nervous System Physiologic Anatomy of the Sympathetic ANS activated mainly by centers in the: Nervous System ○ Spinal cord Preganglionic and Postganglionic ○ brain stem Sympathetic Neurons ○ hypothalamus Physiological Anatomy of the Portions of cerebral cortex (especially in the Parasympathetic Nervous System limbic system) Basic Characteristics of Sympathetic and ○ may transmit signals to the lower Parasympathetic Function centers Mechanisms of Transmitter Secretion ○ influence autonomic control and Removal at Postganglionic Endings ANS operates via visceral reflexes Receptors on the Effector Organ ○ Visceral reflexes - subconscious Two Principal Types of Acetylcholine sensory signals from visceral organs → Receptor the autonomic ganglia, brain stem or Alpha and Beta Adrenergic Receptors hypothalamus → return subconscious Excitatory and Inhibitory Actions of reflex responses directly back to the Sympathetic and Parasympathetic visceral organs to control their activities Stimulation ○ Note: involuntary reflexes involved in GI and urinal function C. The Adrenal Medulla Efferent autonomic signals transmitted to Function of the Adrenal Medulla various organs of the body via 2 major Relation of Stimulus Rate to Sympathetic subdivisions: and Parasympathetic Effects ○ Sympathetic nervous system Sympathetic and Parasympathetic ○ Parasympathetic nervous system “Tone” Note: Controls the visceral functions of the body: Selective Stimulation of Target Organs ○ Arterial pressure by Sympathetic and Parasympathetic ○ GI motility/secretion Systems by “Mass Discharge” ○ Urinary bladder emptying Medullary, Pontine, and Mesencephalic ○ Sweating Control of the Autonomic Nervous ○ Body temperature System ○ Metabolic Rate D. Review Questions E. References Physiologic Anatomy of the Sympathetic F. Appendix Nervous System Shown in Figure 1.: LEARNING OBJECTIVES ○ One of the two paravertebral THE MEDICAL STUDENTS ARE EXPECTED TO MEET THE STANDARD sympathetic chains of ganglia LEARNING OBJECTIVES OF THIS SUBJECT: interconnected with spinal nerves of the 1. DESCRIBE THE ROLES OF THE SYMPATHETIC AND vertebral column PARASYMPATHETIC DIVISIONS OF THE AUTONOMIC NERVOUS ○ Prevertebral/peripheral ganglia SYSTEM. (Celiac, superior mesenteric, 2. DESCRIBE THE PHYSIOLOGICAL CHANGES THAT OCCUR WHEN aorticorenal, inferior mesenteric, THE SYMPATHETIC NERVOUS SYSTEM IS ACTIVATED, hypogastric) INCLUDING EFFECTS ON HEART RATE, BLOOD PRESSURE, ○ Nerves extending from ganglia to AND PUPIL DILATION. different internal organs 3. DESCRIBE THE MECHANISMS REGULATING CEREBRAL BLOOD FLOW, INCLUDING THE ROLES OF CARBON DIOXIDE, OXYGEN, ○ Sympathetic nerve fibers originating in AND BLOOD PRESSURE. spinal cord with spinal nerves between 4. DESCRIBE THE STRUCTURE AND FUNCTION OF THE T1 and L2 pass into the sympathetic BLOOD-BRAIN BARRIER. chain then tissues and organs 5. EXPLAIN THE FUNCTIONS OF CSF, INCLUDING ITS ROLE IN stimulated by sympathetic nerves CUSHIONING AND WASTE REMOVAL. PREPARED BY C.L. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. ESCOTE, 1 J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 then peripheral sympathetic ganglion ○ Postganglionic neurons - originates in either one of the sympathetic chain ganglia OR one of the peripheral sympathetic ganglia Postganglionic fibers travel to destinations from either sources Note: Adrenal medulla is a type of postganglionic tissue and secretes epinephrine → norepinephrine Skeletal motor pathway - only composed of single neuron Note: Spinal origin exits via spinal nerves → paravertebral (side of spinal cord) ○ From chain: → to prevertebral ganglia (away from spinal cord) Sympathetic Nerve Fibers in the Skeletal Nerves Postganglionic fibers may base from sympathetic chain into spinal nerves via gray rami at all levels Small type C fibers Extend to all parts of the body via the skeletal nerves Controls blood vessels, sweat glands, piloerector muscles of hairs About 8% of fibers in average skeletal nerve are sympathetic fibers Segmental Distribution of the Sympathetic Nerve Fibers Sympathetic fibers from the spinal cord segments are distributed based on their Figure 1. Sympathetic Nervous System (Peripheral) origin: ○ T1 fibers: Supply the head and neck. ○ T2 to T6 fibers: Primarily supply the thorax Preganglionic and Postganglionic ○ T7 to T11 fibers: Innervate the Sympathetic Neurons abdomen. Sympathetic pathways - composed of 2 ○ T12 to L2 fibers: Innervate the legs. neurons: Distribution of sympathetic nerves to each ○ Postganglionic neurons organ determined partly by locus in the Preganglionic neurons - cell body lies in embryo from which the organ originated intermediolateral horn of spinal cord ○ Heart with sympathetic nerve fibers from fiber passes through ventral neck portion due to originating in the root of the cord and into neck of the embryo before translocating corresponding spinal nerve into thorax passess through white ramus ○ Abdominal organs receive most of into ganglia of sympathetic sympathetic innervations from lower chain thoracic spinal cord segments Fibers can take 3 courses: synapse with postganglionic Special Sympathetic Nerve Endings in the sympathetic neurons in Adrenal Medullae ganglion they enter Passing of sympathetic nerve fibers without pass up or downward in synapsing from intermediolateral horn of spinal chain and synapse in cord other ganglia of chain Through sympathetic chains then splanchnic pass through variable nerves then into 2 adrenal medullae distances , through End on modified neuronal cells secreting sympathetic nerves, epinephrine and norepinephrine into bloodstream PREPARED BY C.J. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. 2 ESCOTE, J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 Derived from nervous tissue and is actually Preganglionic fibers pass to the controlled postganglionic neurons organ, except for a few cranial parasympathetic nerves. Physiological Anatomy of the Postganglionic neurons are located in the Parasympathetic Nervous System organ's wall. Short postganglionic fibers innervate organ tissues. Parasympathetic postganglionic neurons' location differs from sympathetic ganglia's, as cell bodies are usually in the sympathetic chain or other abdominal ganglia. Basic Characteristics of Sympathetic and Parasympathetic Function Cholinergic and Adrenergic Fibers - Secretion of Acetylcholine or Norepinephrine Cholinergic - secretes acetylcholine ○ All preganglionic neurons in both the SNS and PSNS ○ All postganglionic neurons of PSNS ○ Postganglionic SNS to sweat glands ○ Acetylcholine is called parasympathetic transmitter Adrenergic - secretes norepinephrine ○ Almost all postganglionic neurons of the SNS ○ norepinephrine is called a sympathetic transmitter Mechanisms of Transmitter Secretion and Removal at Postganglionic Endings Secretion of Acetylcholine and Norepinephrine by Postganglionic Nerve Endings Nerve fibers touch the effector cells of the Figure 2. The Parasympathetic Nervous System organs that they innervate or terminate in the connective tissue adjacent to them and usually Note: Vagus nerves will send fibers away from have bulbous enlargements called varicosities head Transmitter vesicles of acetylcholine or Parasympathetic fibers leave CNS via CN III, norepinephrine are synthesized and stored in VII, IX, X; these varicosities ○ Note: S2 - S4 spinal nerves Action potential increases the permeability of the 75% all parasympathetic nerve fibers are in fiber membrane to calcium ions causing the vagus nerves (CN X) terminals or the varicosities to empty their ○ Supplies parasympathetic nerves to contents to the exterior and release the heart, lungs, esophagus, stomach, small transmitters they store. intestine, proximal half of colon, liver, gallbladder, pancreas, kidneys, upper Synthesis of Acetylcholine, Its Destruction portion of uterus After Secretion, and Its Duration of Action CN III → pupillary sphincter and ciliary muscles of eye CN VII → lacrimal, nasal, submandibular glands and fibers from CN VIII to parotid gland Sacral parasympathetic fibers in pelvic nerves at S2 and S3 levels → colon, rectum, urinary Cholinergic nerve endings secrete acetylcholine bladder and lower portion of ureters; also sends and it only persists for a few seconds signals to external genitalia It is then split by acetylcholinesterase bound by collagen and glycosaminoglycans in the local connective tissue into acetate ion and choline Preganglionic and postganglionic The choline formed is transported back into the parasympathetic neurons terminal nerve ending and is used in the Both systems have preganglionic and synthesis of new acetylcholine postganglionic neurons. PREPARED BY C.J. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. 3 ESCOTE, J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 Synthesis of Norepinephrine, Its Removal, Two Principal Types of Acetylcholine and Its Duration of Action Receptor Muscarinic and Nicotinic Receptors Begins in axoplasm of terminal nerve endings of Muscarine (from toadstools) - only activates adrenergic fibers, completed in secretory muscarinic receptors vesicles ○ G proteins as signal mechanism ○ Found in all effector cells stimulated by postganglionic cholinergic neurons of the SNS or PSNS Nicotine - only activates nicotinic receptors ○ Ligand-gated ion channels ○ Found in autonomic ganglia at the Extra step in adrenal medulla synapses between preganglionic and postganglionic neurons of SNS and Three ways norepinephrine is removed from the PSNS secretory site ○ Present in neuromuscular junctions in 1. 50-80% of secreted norepinephrine is skeletal muscle reuptaken into the adrenergic nerve Acetylcholine - activates both receptors endings through active transport 2. Diffusion into surrounding fluids and into Alpha and Beta Adrenergic Receptors the blood 3. Small amounts are destroyed by enzymes such as monoamine oxidase in nerve endings and catechol-O-methyltransferase in tissues (liver) When secreted directly into tissues, norepinephrine is active for only a few seconds but when in blood, it can remain active for 10 to 30 seconds Receptors on the Effector Organ Receptors are membrane bound prosthetic group to a protein molecule that causes conformational change to the protein molecule when bound to a transmitter Beta-receptors also use G proteins for signalling through: Norepinephrine excites mainly alpha receptors but excites the beta receptors to a lesser extent Epinephrine excites both types of receptors Excitation or Inhibition of the Effector Cell by approximately equally Changing Its Membrane Permeability Opening or closing of ion channels Excitatory and Inhibitory Actions of Opening of Sodium and Calcium ion channels Sympathetic and Parasympathetic allows influx of said ions and depolarizes the cell Stimulation membrane which excites the cell Opening of Potassium channels allows the diffusion of potassium ions outside of the cell which inhibits the cell as it creates hyper negativity inside the cell Receptor Action by Altering Intracellular “Second Messenger” Enzymes Activates or inactivate an enzyme inside the cell, usually through attaching to a receptor protein protruding to the inside of the cell Binding of norepinephrine increases the activity of the enzyme adenylyl cyclase on the inside of the cell which forms cyclic adenosine monophosphate (cAMP) cAMP then initiates many different intracellular processes PREPARED BY C.J. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. 4 ESCOTE, J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 can cause vasodilation in some cases via beta adrenergic action. b. Parasympathetic: Little effect on blood vessels. 7. Arterial Pressure a. Sympathetic: Increases blood propulsion and peripheral resistance, raising pressure. b. Parasympathetic: Decreases heart rate, causing slight drop in pressure. 8. Other Functions a. Sympathetic: Inhibits ducts (liver, This table lists effects on different visceral functions of gallbladder, bronchi) and increases the body caused by stimulating either the metabolic functions like glucose release, parasympathetic nerves or the sympathetic nerves. glycogenolysis, muscle strength, and basal metabolic rate. Sympathetic and parasympathetic stimulation b. Parasympathetic: Excites ducts (liver, can cause excitatory or inhibitory effects, gallbladder, bronchi) and assists in depending on the organ. sexual function. These systems often act reciprocally, meaning when one excites, the other inhibits. Most organs are dominantly controlled by either The Adrenal Medulla the sympathetic or parasympathetic system. There’s no universal rule for predicting whether Function of the Adrenal Medulla stimulation will excite or inhibit an organ. Sympathetic Stimulation To understand these systems, it's important to learn their specific effects on each organ. Sympathetic Stimulation causes the adrenal medullae to release epinephrine (80%) and norepinephrine Effects of Sympathetic and Parasympathetic (20%) into the blood, affecting all body tissues. Stimulation on Specific Organs Effects on Organs: 1. Eyes ○ Norepinephrine: a. Sympathetic: Dilates pupil (contracts Constricts most blood vessels, meridional fibers). increases heart activity, inhibits b. Parasympathetic: Constricts pupil gastrointestinal tract, dilates (contracts circular muscle) and controls pupils. lens focusing for near vision. similar effects to direct SNS 2. Glands stimulation a. Parasympathetic: Stimulates nasal, Greater vasoconstriction lacrimal, salivary, and upper (greater effect on total gastrointestinal glands to secrete watery peripheral resistance and Blood fluid. pressure) b. Sympathetic: Causes concentrated ○ Epinephrine: enzyme-rich secretions and Strong cardiac stimulation due vasoconstriction, reducing gland to beta receptor activation; secretion. Stimulates sweat glands Greater cardiac stimulation (cholinergic fibers). (greater effect on cardiac 3. Apocrine Glands (Axilla) output) a. Sympathetic: Stimulates secretion of Weaker vasoconstriction in thick, odoriferous fluid; no muscles, leading to less parasympathetic effect. increase in total peripheral 4. Gastrointestinal System resistance. a. Parasympathetic: Increases peristalsis Metabolic Effects: and relaxes sphincters, enhancing ○ Epinephrine has a 5-10x greater motility and gland secretion. metabolic effect than norepinephrine. b. Sympathetic: Inhibits peristalsis, (100% increase in the metabolic rate) increases sphincter tone, slows ○ Increases overall metabolic rate, propulsion, may reduce secretion. glycogenolysis, and glucose release. 5. Heart Prolonged Effects: a. Sympathetic: Increases heart rate and ○ Hormonal effects last 2-4 minutes, contraction strength. much longer than direct sympathetic b. Parasympathetic: Decreases heart rate stimulation. and contraction strength. Dual Stimulation Mechanism: 6. Blood Vessels ○ Organs are stimulated both by direct a. Sympathetic: Constricts vessels sympathetic nerves and hormones (mainly abdominal viscera and skin); PREPARED BY C.J. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. 5 ESCOTE, J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 from the adrenal medullae, providing Purpose of tone: Tone allows the nervous system to redundancy. either increase or decrease the activity of organs. ○ Loss of one system can be compensated by the other. ❖ Example (Sympathetic tone) Additional Benefit: Sympathetic tone keeps systemic ○ Epinephrine and norepinephrine can arterioles constricted to half their stimulate cells not directly innervated diameter. by sympathetic fibers, increasing Increased stimulation leads to more metabolic rates body-wide. constriction. Adrenal Medulla Support the SNS Function Decreased stimulation leads to ○ SNS – 2 ways (direct by sympathetic vasodilation. nerves, indirectly by the Adrenal Without a sympathetic tone, only medullary hormones) vasoconstriction could occur. ○ Dual mechanism provides safety factor ❖ Example (Parasympathetic tone) ○ Capability of NE and Epinephrine to Parasympathetic tone in the stimulate structures not innervated by gastrointestinal tract is essential for direct stimulation of sympathetic fibers normal function. (e.g. metabolic rate of all cells) Removal of parasympathetic supply Autonomic Reflexes (e.g., cutting the vagus nerve) causes ○ Baroreceptor reflex severe gastric and intestinal inactivity, Stretch receptors (ICA bulb and leading to constipation. Arch of Aorta) The brain can adjust parasympathetic Inhibits sympathetic impulse tone to increase or decrease and excites the PSNS gastrointestinal activity. Decrease in BP Basal Secretion: ○ Gastrointestinal Autonomic reflex Epinephrine: 0.2ug/kg/min Smell/sight of food/ presence of Norepinephrine: 0.05ug/kg/min food in the mouth Secretory glands Tone Caused by Basal Secretion of Salivary Epinephrine and Norepinephrine by the Digestive juices ○ Defecation Adrenal Medullae ○ Gastrocolic / Gastroduodenal / Duodenocolic Reflexes The adrenal medullae normally secrete about ○ Other Reflexes: 0.2 µg/kg/min of epinephrine and 0.05 µg/kg/min Micturation (bladder stretch) of norepinephrine. Sexual reflexes These levels help maintain near-normal blood pressure even if direct sympathetic pathways to Relation of Stimulus Rate to Sympathetic and the cardiovascular system are removed. This shows that sympathetic tone comes not Parasympathetic Effects only from direct nerve stimulation but also from The autonomic nervous system differs from the skeletal basal hormone secretion. nervous system in terms of the frequency of nerve stimulation required for activation. Effect of Loss of Sympathetic or Low stimulation frequency is sufficient for full Parasympathetic Tone after Denervation activation of the autonomic nervous system (ANS). When a sympathetic or parasympathetic nerve Sympathetic and parasympathetic nerves is cut, the organ it innervates loses its tone require only a few discharges every few Example: Cutting sympathetic nerves causes seconds to maintain normal function. vasodilation in blood vessels in seconds Full activation of ANS occurs at 10-20 Over time, intrinsic tone in smooth muscles impulses/sec, compared to 50-500+ compensates for this loss, restoring normal impulses/sec for the skeletal nervous system. vasoconstriction through chemical adaptations, not nerve signals Sympathetic and Parasympathetic “Tone” In other organs, similar intrinsic compensation occurs, returning function to normal basal level Sympathetic and parasympathetic tone - both In a parasympathetic system, compensation systems are continually active and have baseline activity may take longer, sometimes, months. levels known as tone Example: After cardiac vagotomy (cutting the parasympathetic nerve in the heart, the heart Continuous activity of the ANS rate can rise to 160 beats per minute in a dog and remain elevated for months. 1 impulse every few seconds Full activation 10-20 times/sec PREPARED BY C.J. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. 6 ESCOTE, J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 Leads to the alarm or stress response, affecting the entire body. Isolated Portions of the Sympathetic Nervous System Heat regulation. Sympathetic control over sweating and skin blood flow occurs without affecting other organs. “Local reflexes”. ○ caused by sensory afferent fibers ○ Example: Heating a skin area leads to vasodilation and enhanced sweating; cooling causes the opposite (vasoconstriction, reduced sweating). Gastrointestinal reflexes ○ Sympathetic reflexes controlling gut Baseline blood flow: At the start, the blood flow in the function often bypass the spinal cord. arm is around 200 mL/min (considered normal). ○ Nerve pathways pass from the gut to the paravertebral ganglia and back, Effect of test dose of norepinephrine (before influencing motor or secretory activity. sympathectomy): - Administering norepinephrine causes a small drop in blood flow, indicating The Parasympathetic System Usually Causes vasoconstriction, but the effect is Specific Localized Responses. minimal. Stellate ganglionectomy (sympathectomy): Parasympathetic System Control - After the stellate ganglion (a part of the Highly specific functions sympathetic nervous system) is ○ Cardiovascular reflexes removed at around 2 weeks, the blood act on the heart only to increase flow increases significantly, reaching or decrease its rate of beating over 400 mL/min. with little direct effect on its Post-sympathectomy adaptation: force of contraction - Following sympathectomy, there is a ○ Glandular secretion gradual decline in blood flow over mouth glands time, but it stabilizes above normal stomach glands levels after a few weeks, showing an ○ Rectal emptying reflex initial vasodilation followed by partial does not affect other parts of recovery. the bowel to a major extent. Supersensitization: - At around 5 weeks, the same dose of Allied Parasympathetic Functions norepinephrine is given again, and it salivary secretion can occur independently of causes a dramatic reduction in blood gastric secretion, and pancreatic secretion flow compared to the frequently occurs at the same time. pre-sympathectomy response. rectal emptying reflex often initiates a urinary - This demonstrates supersensitization, bladder emptying reflex where the blood vessels become more The bladder emptying reflex can help initiate sensitive to norepinephrine following the rectal emptying. loss of sympathetic tone. “Alarm” or “Stress” Response of the Sympathetic Nervous System Overall effect: Sympathectomy initially increases blood When large portions of the sympathetic nervous system flow due to loss of sympathetic control, but over time, discharge at the same time—that is, a mass vessels regain tone through other mechanisms, and they discharge—this action increases the ability of the body become highly sensitive to norepinephrine. to perform vigorous muscle activity in many ways, as summarized in the following list: Selective Stimulation of Target Organs by Increased arterial pressure Sympathetic and Parasympathetic Systems Increased blood flow to active muscles by “Mass Discharge” concurrent with decreased blood flow to organs such as the gastrointestinal tract and the The Sympathetic System Sometimes kidneys that are not needed for rapid motor activity Responds by Mass Discharge Increased rates of cellular metabolism Mass Discharge throughout the body Simultaneous activation of nearly all portions Increased blood glucose concentration of the sympathetic nervous system. Increased glycolysis in the liver and in muscle Occurs during fright or severe pain (e.g., due Increased muscle strength to hypothalamus activation). Increased mental activity PREPARED BY C.J. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. 7 ESCOTE, J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 Increased rate of blood coagulation Some of the most important factors controlled in Sympathetic System the brain stem are: The sum of these effects permits a person to ○ Arterial pressure perform far more strenuous physical activity ○ Heart rate than would otherwise be possible. ○ Respiratory rate Mental or physical stress can excite the sympathetic system. Control of Brain Stem Autonomic Centers by The purpose of the sympathetic system is to Higher Areas provide extra activation of the body in states of stress, called the sympathetic stress Signals from the hypothalamus and even from response. the cerebrum can affect activities of almost all the brainstem autonomic control centers. Activation in Emotional States Example The sympathetic system is especially strongly ○ posterior hypothalamus—can activate activated in many emotional states. the medullary cardiovascular control Example: centers strongly enough to increase ○ In the state of rage, which is elicited to a arterial pressure to more than twice great extent by stimulating the normal hypothalamus, signals are transmitted ○ Other hypothalamic centers control downward through the reticular Body temperature formation of the brain stem and into the Salivation and spinal cord to cause massive gastrointestinal activity sympathetic discharge. Bladder emptying behavioral responses are mediated through the Sympathetic Alarm Reaction following the fight-or-flight reaction because an animal ○ hypothalamus in this state decides almost instantly whether to ○ reticular areas of the brain stem stand and fight or to run. ○ autonomic nervous system The sympathetic alarm reaction makes the animal’s subsequent activities vigorous. Medullary, Pontine, and Mesencephalic Control of the Autonomic Nervous System Many neuronal areas in the brain stem reticular substance and along the course of the tractus solitarius of the medulla, pons, and mesencephalon, as well as in many special nuclei (Figure 61-6), control different autonomic functions, such as: ○ Arterial pressure ○ Heart rate ○ Glandular secretion in the gastrointestinal tract ○ Gastrointestinal peristalsis ○ Degree of contraction of the urinary bladder Figure 61-6. Autonomic control areas in the brain stem and hypothalamus. PREPARED BY C.J. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. 8 ESCOTE, J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 and potential mechanisms for blood flow CEREBRAL BLOOD FLOW, CEREBROSPINAL regulation by astrocytes. FLUID, AND BRAIN METABOLISM ○ The pial arteries lie on the glia limitans, and the penetrating arteries are Cerebral Blood Flow surrounded by astrocyte foot processes. ○ The astrocytes also have fine processes that are closely associated with synapses. Virchow-Robin Space ○ Between pia mater and pial arteries ○ An extension of the subarachnoid space Regulation of Cerebral Blood Flow Normal Blood Flow ○ 50-65ml/100g of brain tissue per minute ○ 750-900ml/min (15% of cardiac output) Cerebral blood flow is highly related to tissue metabolism. Blood flow of the brain is supplied by four large Factors believed to contribute to cerebral arteries – two carotid and two vertebral blood flow regulation arteries – that merge to form the circle of ○ CO2 concentration Willis at the base of the brain. ○ Hydrogen ion +(H) concentration ○ Internal carotid artery (right and left) ○ O2 concentration ○ Middle cerebral artery ○ Substances released from astrocytes ○ Basilar artery The arteries arising from the circle of Willis Regulation of Cerebral Blood Flow travel along the brain surface and give rise to CO2 or H+ concentration pial arteries, which branch out into smaller vessels called penetrating arteries and arterioles. ○ If there is a blockage (stenosis or occlusion) in one part of a vessel within the circle of Willis, blood flow from other arteries can reroute to compensate. Increase in CO2 concentration in the arterial blood perfusing the brain greatly increases cerebral blood flow ○ Image above: A 70% increase in arterial blood pressure of CO2 (pCO2) approximately doubles cerebral blood flow. CO2 + H2O → HCO2 + H(+) ○ CO2 is believed to increase cerebral blood flow by combining first with water in the body fluids to form carbonic acid, with subsequent dissociation of this acid to form H+. H(+) then causes vasodilation of the cerebral vessels The penetrating vessels dive down into the brain ○ The dilation is almost directly tissue, giving rise to intracerebral arterioles, proportional to the increase in H+ which eventually branch into capillaries where concentration up to a blood flow limit of exchange among the blood and the tissues of about twice normal O2, nutrients, carbon dioxide (CO2), and Other substances that increase acidity of the metabolites occurs. brain tissue and therefore increase H+ Relation of astrocytes with the intracerebral concentration will likewise increase cerebral arterioles blood flow ○ The image above illustrates the ○ Lactic acid architecture of cerebral blood vessels ○ Pyruvic acid PREPARED BY C.J. AYCOCHO, I.V. AREVALO, C.S. AVES, A.H., AYANA, T.K., BENGUET, M.J., BURZON, A., CALLO, R., DE JESUS, B. DUMAS, M.S., EBONITE, H.G., EMBUDO, L.F. 9 ESCOTE, J.A., FURIO, A.R.G., GOMEZ. (YL1-A3)  The Autonomic Nervous System and the Adrenal Medulla; Cerebral Blood Flow, Cerebrospinal Fluid, and Brain Metabolism – Week 2 ○ Any other pacific material formed by most synapses and large foot processes that tissue metabolism are closely opposed to the vascular wall. Excitatory neurons produce Glutamate → Importance of Blood Flow Control by CO2 and increased intracellular Ca ion inside Astrocytes H+ → vasodilation of blood vessels Vasodilation is mediated by several Increased H+ concentration greatly depresses vasoactive metabolites released from neuronal activity astrocytes. Increased H+ concentration also elicits ○ Mediator from astrocyte to blood vessel increased blood flow, which in turn carries H+, – not yet clear (potentially: nitric oxide, CO2, and other acid-forming substances away metabolites of arachidonic acid, from the brain tissue potassium ions, adenosine, and other Loss of CO2 removes carbonic acid from the substances generated by astrocytes in tissues → reduces the H+ concentration back response to stimulation of adjacent toward normal. excitatory neurons) Maintains a constant H+ concentration in the cerebral fluids → maintains a normal, constant Cerebral Blood Flow Autoregulation level of neuronal activity Regulation of Cerebral Blood Flow Oxygen Concentration 3.5 (±0.2) ml of O2/100g of brain tissue / min → rate of O2 utilization ○ If brain blood flow becomes insufficient to supply O2, the O2 deficiency almost immediately causes vasodilation, returning the brain blood flow and transporting O2 to the cerebral tissues to near normal. 35-40 mmHg pO2 normal range ○