Introduction to Pathophysiology and Cellular Basis of Disease Part 3

Normal Function of the Nervous System ● Major Divisions of the CNS ○ Spinal cord ○ Brain stem - medulla, oblongata, pons, and midbrain ■ Responsible for autonomic response (heartbeat, brain, lung) ○ Cerebellum ■ LEARNED motor movements - movements we don’t have to think about anymore to carry out ○ Diencephalon - thalamus, hypothalamus ■ Body temp, appetite, sexual reproduction function, part of the LIMBIC system (emotion) ○ Cerebrum - left and right cerebral hemispheres, basal ganglia, hippocampus, and amygdala ■ Cognition, executive function ● Brain anatomy ○ Lobes of Cerebral Cortex ○ ○ ● Internal components of brain ○ Somatosensory map ○ ■ ■ ● Aka somatotopic map People who are blind → brain plasticity makes touch stronger connection Language Circuit ○ ■ ■ ■ Wernicke’s area - processes auditory input for language (important for understanding speech) ● CREATES MEANING (emotional/cognitive content) Angular gyrus - part of temporal lobe. Combines AUDITORY and OTHER SENSES from the somatosensory cortex, visual cortex, primary auditory area and FEEDS INTO WERNICKE’S AREA Broca’s area - receives input FROM WERNICKE’S and produces intelligible speech. Lies NEAR PRIMARY MOTOR AREA that controls tongue movements that form words ● Language is developed on LEFT SIDE of brain for most people ● ● ● RIGHT SIDE = idiosyncratic understanding of things. Obscure, weird meaning of things ● Relationship BTWN WERNICKE AND BROCA = BIDIRECTIONAL ■ Receptive aphasia - language is NONSENSE, bc ability to understand is damaged ■ Expressive aphasia - language is BROKEN. Injury in broca. CAN UNDERSTAND, CANNOT EXPRESS (verbally or write it out) ■ STROKE - damage to either 3 on LEFT SIDE usually Brodmann’s brain - very specific reference points that locate brain activity to body function CNS Anatomy ○ Glial cells - NON-NEURONAL supportive cells of the nervous system (two types of cells in brain: neuronal and glial cells) ■ Astrocytes - part of BBB. surround capillaries in brain and create physical barrier that regulates what crosses ■ Oligodendrocytes - provide myelination to axons within CNS ■ Ependymal cells - type of epithelial cell that forms walls of cerebral ventricle membrane ○ Meninges and Ependymal Cells ■ Meninges - three membranes that line the skull (dura matter, arachnoid membrane, pia matter) ● ○ ■ By layers: ■ 1. Cranial skull - protects brain matter ■ 2. Dura matter ■ 2a. Superior sagittal sinus - veins go through ■ 3. Arachnoid membrane ■ 4. Subarachnoid membrane - filled with blood vessels and CSF (yellow color) Ependymal cells ● ○ type of epithelial cell that forms walls of cerebral ventricle membrane ○ Cerebral ventricles - cavities WITHIN brain ■ Function: produce/secrete CSF → fluid filled ventricles = keeps brain buoyant and cushioned ● Ventricles of the Brain ■ ■ Ventricular system ● 4 ventricles ALL CONNECTED ○ Right lateral ventricle (purple. Located cerebral hemi) ○ Left lateral ventricle (green. Located cerebral hemi) ○ 3rd ventricle (located in diencephalon) ○ 4th ventricle (located in hindbrain) ● Choroid plexus - produces CSF Kidney of brain. Takes blood, filters it out and produces CSF → CSF moves through ventricles, all the way to cerebral spinal canal Cerebrospinal fluid (CSF) - fluid occupying ventricular system ● Composition of CSF compared to plasma ■ → GOAL: REDUCE/regulate EXCITABILITY. Decrease chance of firing AP. reduce seizure potential ○ Sodium: less Na in CSF (153 vs 147) ○ Potassium: way less K in CSF (4.7 vs 2.9) ■ Decreased CSF concentration = K in plasma move out → takes positive charge with it → LOWERS membrane potential (more negative) ○ Magnesium: more Mg in CSF (0.6 vs 1.1) ■ Extracellular magnesium interact with sodium channels → decreases permeability. Reduce excit ■ Magnesium in cardiac pts ● Low mapnesium related to HTN (smooth muscles in blood vessels TIGHT→ BP incre ○ If you increase Mg = dec HTN ○ Amino acids: way less in CSF (2.6 vs 0.7) ■ Amino acids = neurotransmitters. No NT = no AP ○ Proteins: way less in CSF (7 vs 0.03) CSF circulation - GOAL: keep CSF at optimal concentration of O2/CO2, ion, glucose, everything brain needs ● There is a choroid plexus associated with each ventricle ○ CSF produced, goes through all ventricles and EXITS AT 2 CHANNELS: ■ MEDIAN and RIGHT LATERAL APERTURE ■ Channels connect to SUBARACHNOID SPACE (SS) ● CSF travels to SS and into ARACHNOID GRANULATION (AG) ○ CSF gets drained into sagittal vein/sinus. Leaves brain into general circulation ○ ■ ■ ● ● Blood Brain Barrier (BBB) ○ 2 fluids in CNS (CSF and brain extracellular fluid: BECF) ■ Production of BECF → done by BBB filtering plasma at MICROCIRCULATION ○ BBB = 3 layers ■ 1. Tight junction (brain capillary endothelial cells) ● Protein adhesion that joins individual endothelial cells together. Ensures everything goes through 2 layers of endothelial cells ○ Water and O2/CO2 = moves freely through ○ LIPIDS = moves freely. Sedating drugs can pass BBB ○ Sodium = channel ○ Glucose = facilitated transporter ■ 2. Basement membrane ■ 3. Endfeet - ASTROCYTES ● 2 more membranes to cross to get to BECF ○ ■ LEAKY REGIONS of BBB - Circumventricular Organs ■ Locations of easy access to cross into BBB ■ Median eminence, posterior pituitary, OVLT, subfornical organ, subcommissural organ, pineal gland, area postrema ● Ex. median eminence (located close to hypothalamus) ○ Infection (pneumonia) → release of cytokines → to induce fever, binds to median eminence ● CNS Systems using modulatory NT ○ Patterns of synaptic connections (cell to cell ratio. # of cells that originating message to # of receiving cells) ■ Spatially focused: low ratio between 1st to 2nd order and so forth ● Connection good at TASK ORIENTED THINGS (ex.motor respon) ■ Widely divergent: few cells to multiple other cells/regions of brain ● Controls OVERALL LEVELS OF EXCITABILITY of large/multiple areas of brain ○ COMPLEX BEHAVIOR/TRAITS ■ Ex. sleep/wake cycle, attention ● Neurotransmitter systems (4 systems: NE, Serotonin, Dop, ACh) ○ Norepinephrine System ■ LOCUS COERULEUS - region where NE system originates ● Makes WIDESPREAD PROJECTIONS to diff regions of brain ■ Behaviors influenced: ● SLEEP/WAKE CYCLE ○ Circadian patterns of attentiveness, water agitation regulated by this system ● ATTENTION ○ How many things can you focus on ■ Ex. stratten - drug for ADHD. acts on this system ○ Regulated by a lot of INHIBITION ■ Function of neo/prefrontal cortex ● Inhibits things so you focus on important details ■ Function of amygdala (fear) ● Determines WHAT to focus on (danger related) ■ Function of hippocampus ● Short term memory ● MOOD (not directly influenced by NE) ○ Indirectly affects mood by interacting with serotonin system ○ Serotonin System ■ RAPHE NUCLEI - region where Serotonin system originates (brainstem) ● Serotonergic cells that make WIDESPREAD PROJ to diff regions ○ Many of same NE regions are affected by serotonin system ■ Behaviors influenced:(remember ecstasy. Floods serotonin throughout brain. Prevents reuptake. Also causes reuptake transporters to act in reverse and dump out serotonin to synapse. EFFECTS = MOOD (euphoria), AWAKE, MOTOR RESTLESSNESS (dance 5/6hrs straight), HYPERTHERMIA) ○ ○ ● SLEEP/WAKE CYCLE ● MOOD ● TEMPERATURE CONTROL ● MOTOR EXCITATION Dopamine System → FOR TEST, REMEMBER SPECIFIC NAMES OF CIRCUIT AREAS ■ Far less global than the NE or serotonin system or ACh ■ 2 KEY CIRCUITS ● 1) SUBSTANTIA NIGRA (black substance bc how it stains) origin ○ A part of BASAL GANGLIA (one of 3 brain regions involved in motor movements) → project to caudate nucleus and putamen (also in basal ganglia) ○ Behavior: ■ Help modify or adjust VOLUNTARY motor movements ● If overstimulated → motor restlessness ● 2) reward pathway ○ VENTRAL TEGMENTAL AREA (VTA) → projects to: ■ PREFRONTAL CORTEX ■ NUCLEUS ACCUMBENS ■ Behavior: ■ Any time you do or experience something that brings you pleasure and makes you want to do it again ● Ex. eating good food, sex, tv shows anything highly stimulating ● Drugs are high potential for abuse because causes compulsion to continue doing related activity ■ Drives motivation to do anything, however small events Acetylcholine ■ 3 regions where it originates (no need to memorize) ● Pontomesencephalotegmental complex ● Nucleus basalis ● Septal nuclei ■ Project WIDELY throughout brain ■ Behaviors: ● SLEEP/WAKE ● Also mad as a hatter - ACh toxicity ○ Shows that ACh plays role in COGNITIVE PROCESSING (perceive and think) ■ If we block ACh = cause delirium