Quiz 2 Flashcards

1
Q

Nonessential

A
Synthesized in the body; 
Alanine 
Asparagine
Aspartate
Glutamate
Serine
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2
Q

Conditional Essential

A
Synthesis can be limited under special pathophysiological conditions (prematurity of infants or those with severe catabolic distress)
Arginine
Cysteine
Glutamine
Glycine
Proline
Tyrosine
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3
Q

Essential

A
Indispensible aa; can't be synthesized de non so must be supplied by diet
Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Threonine
Tryptophan 
Valine
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4
Q

ketogenic

A

AA that are converted to acetyl CoA or acetoacetate so precursors of FA and ketone bodies

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5
Q

Glucogenic

A

AA converted to precursors for glucose synthesis like alpha ketogluterate, succinyl coA, fumerate, pyruvate, oxaloacetate

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6
Q

Both ketogenic and glucogenic

A

Isoleucine, Phenylalanine, Tyrosine, Tryptophan, Threonine

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7
Q

Stereoisomerism in alpha- AA

A

L and D configurations ; most in nature are L

AA are all chiral except glycine (enantiomers)

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8
Q

Nonpolar, aliphatic R groups

A

Glycine, Alanine, Proline, Valine, Leucine, Isoleucine, Methionine

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9
Q

Aromatic R groups

A

Relatively nonpolar; absorb UV (Tryptophan absorbs most followed by tyrosine the Ph)
Tryptophan, Phenylalanine, Tyrosine

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10
Q

Polar, uncharged R groups

A

Serine, Threonine, Cysteine, Asparagine, Glutamine

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11
Q

Positively Charged R groups

A

Lysine, Arginine, Histidine

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12
Q

Negatively charged R groups

A

Aspartate, Glutamate

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13
Q

Reversible formation of a disulfide bond by the oxidation of 2 cysteine

A

Hair straightening (safer; most representative aa in hair)

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14
Q

Uncommon amino acids/ modifications of aa

A

Hydroxyproline and hydroxylysine found in collagen

Addition of phosphate, methyl, adenosine (reversible)

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15
Q

AA not found in proteins

A

Ornithine (urea cycle, bad breath) and citrulline (byproduct of production of nitric oxide- vasodilator)

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16
Q

Non-ionic or zwitterion forms of AA

A

Zwitterion- neutral molecules with a positive and negative electrical charge though multiple positive and negative charges can be present

a characteristic pH, called the isoelectric point (pI), the negatively and positively charged molecular species are present in equal concentration; characteristic pH at which the net electric charge is zero

Effects of chemical environments on pka

pka -COOH 1.8-2.4 [4.8?]
pka -NH3 8.8-9.7 [10.6]
isoelectric pt: 5.5-6.2

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17
Q

Titration of amino acids

A

pI=1/2 (pka1+pka2) of the pkas closest to each other? (+1, -1)

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18
Q

Proteins are polymers built from aa joined by peptide bonds

A

usually peptides- have ~50 or fewere AA vs proteins (1 or more polypeptide)

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19
Q

Formation of peptide bond by condensation

A

Removal of water (OH from carboxy and H from amine)

AA residues; not rotatable around peptide bond but can rotate around alpha carbon

As increase residues, increase of MW

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20
Q

Conjugated proteins

A

Lipoproteins, Glycoproteins, phosphoproteins, hemoproteins, Flavoproteins, metalloproteins

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21
Q

Levels of structure in proteins

A

Primary (aa string), secondary (alpha helix or beta pleated sheets; H bonds), tertiary (folding; polypeptide chain) quaternary (assembled subunits)

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22
Q

A change of a single aa can alter the function of protein

A

Ex. sickle cell anemia Glu–> Val

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23
Q

Collagen Synthesis

A

Need vitamin C (not enough OH without it- can’t attain full strength)

Hydroxyproline and hydroxylysine found in collagen

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24
Q

Diseases related to collagen

A

Scurvy, Osteogenesis imperfecta, Ehlers- Danlos Syndrome, Spondylopiphyseal Dyplasia

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25
Q

Elastin

A

highly elastic protein in CT; allows many tissues in body to resume their shape after stretching or contracting

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26
Q

Production of most plasma proteins occurs in the LIVER

A

Human serum albumin, osmolyte and carrier protein
α-fetoprotein, the fetal counterpart of serum albumin
Soluble plasma fibronectin, forming a blood clot that stops bleeding
C-reactive protein, opsonin on microbes
Acute phase protein

factors in hemostasis and fibrinolysis, carrier proteins, hormones, prohormones and apolipoproteins

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27
Q

The planar peptide group

A

Carbony O has partial neg. and amide N partial Pos. setting up small eltric dipole. All peptide bonds in proteins occur in trans configuration

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28
Q

alpha helix and beta pleated sheets

A

Alpha helix has cross linked disulfide bonds that make it tough, protective [alpha keratin of hair, feathers, nails]

Beta sheets can be parallel or antiparallel (H bonds are straight); soft/flexible [silk fibroin]

collagen triple helix (high tensile strength, without stretch); collagen of tendons, bone matrix

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29
Q

Pathways that contribute to proteolysis

A

process by which cells control the abundance and folding of the proteome, and consists of a highly interconnected network that integrates the regulation of gene expression, signaling pathways, molecular chaperones and protein degradation systems

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30
Q

Histones

A

Each chromosome consists of a single molecule of DNA complexed with an equal mass of proteins. Collectively the DNA associated with these proteins is called chromatin. Most of these proteins are histone; Have Arg and Lys bind phosphate groups (neg) form nucleosomes

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31
Q

Proteins denature and renature

A

Native state; catalysis active–> (addition of urea and mercaptoethanol) unfolded state, inactive (DISULFIDE cross links reduced to yeild Cys)–> Native, catalytically active state; disulfide cross links correctly reformed

Due to temp, pH

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32
Q

Quaternary structure

A

polypeptide chain (collagen) vs 2 beta and 2 alpha chains in Hemoglobin associated with Iron and Heme

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33
Q

Nervous System

A

Have 100 billion nerve cells (neurons) in human brain with each connected to ~10,000 others= 100 trillion nerve connections

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34
Q

CNS

A

Brain and spinal cord

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35
Q

PNS

A

Somatic (voluntary)

Autonomic (Involuntary)- Sympathetic (fight/flight, epinephrine) vs Parasympathetic (rest/digest, acetylcholine)

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36
Q

Neuron Morphology

A

Cell body (perikaryon, soma; has nucleus; metabolic and synthesis center), axon (myelinated, emerges from axon hillock [final site where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon]), dendrites

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37
Q

Dendrites

A

Typically short, small processes emerging and branching off the cell body; USUALLY COVERED WITH MANY SYNAPSES [PRINCIPAL SIGNAL RECEPTION AND PROCESSING SITE]; large number and extensive arborization of dendrites allows a single neuron to receive and integrate signals from many other nerve cells;

“changes in dendritic spines are of key importance in the constant changes of the neural plasticity that occurs during embryonic brain development and underlies adaptation, learning, and memory postnatally”

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38
Q

Axon

A

Conduct AP from cell body to synaptic terminal (allow rapid communication), most neurons have only one axon, typically longer than its dendrites, axonal processes vary in length and diameter (motor neuron axons innervate the foot muscles have lengths of nearly a meter)
Terminals (Boutons)- activated by transmitter and will shut down release and synthesis of Neurotransmitters

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39
Q

Astrocyte

A

most abundant CNS glial cell; star shaped, uptake of transmitters and potassium, produce growth factors and neuroactive factors, Help form the blood brain barrier, regulates interstitial fluid composition, provides structural support and organization to the CNS, assists with neuronal development, replicates to occupy space of dying neurons

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40
Q

Ependymal Cell

A

CNS glial cell; Epithelial like cells that form a single layer lining the fluid filled lines ventricles of brain and spinal cord, lining the ventircles of the cerebrum, columnar ependymal cells extend cilia and microvilli from the apical surfaces into the ventricles, assists in the production and circulation of cerebrospinal fluid

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41
Q

Microglial

A

CNS glial cell; not interconnected unlike the others, normally rare but common at sites of injury/ neurodegeneration, motile cells, constantly used in immune surveillance of CNS tissues, when activated by products of cell damage or by invading microorganisms, the cells retract their processes, begin phagocytosing the damage or dnager related material and behave as APCs, phagocytic cell that move through CNS, protects the CNS by engulfing infectious agents and other potential harmful substances

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42
Q

Oligodendrocyte

A

CNS glial cell; extend many processes, each of which becomes sheet like and wraps repeatedly around CNS axons, many are needed to cover entire length of axon, during wrapping, most cytoplasm gradually moves out of the growth extension leaving mutliple compacted layers of cell membrane called myelin; myelinates and insulates CNS axons, allows faster AP propagation along axon in CNS (myelin sheath electrically insulates axon and facilitates rapid transmission of nerve impulses)

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43
Q

Schwann Cell (Neurolemmocyte)

A

PNS glial cell; surround and insulate PNS axons and myelinate those having large diameters, allows faster AP propagation along axon in PNS

Schwann cells become aligned along axon and extend a wide cytoplasmic process to encircle it–> the spiral wrapping becomes compacted layers of cell membrane (myelin) as cytoplasm leaves the growing process

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44
Q

Gray vs White matter

A

Within brain and spinal cord, regions with tracts of myelinated axons compromise white matter while regions rich in neuronal perikarya (cell body of neuron with nucleus) and astrocytes compromise gray matter

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45
Q

Cell membrane

A

phospholipid bilayer; amphipathic

palmitate (16, saturated) and oleate (18,cis unsaturated)

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46
Q

unusual cell membrane

A

Archael bacteria (proks with no nucleus) have lipids with ether bonds instead of esters (bacteria/eukarya); opposite stereochemistry, branched chains

Biological membranes need to be fluid to allow proteins to move around and to respond to external deformations and damage. Likewise, they need to be impermeable to protons and other charged ions, to allow formation of EC gradient that powers life [lipids in our cells have these properties but only in a narrow range of temp]

Archael lipids form membranes with these properties over a wide range of temp. from freezing cold to boiling hot

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47
Q

selectively permeable membrane

A

size and charge affect the rate of diffusion: hydrophobic molecules (CO2, O2, N2)> small, uncharged polar molecules (H20, indole, glycerol)>large uncharged polar molecules (glucose, sucrose; can’t passively diffuse)> ions (lowest permeability, cant passively diffuse)

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48
Q

Different Membrane Proteins

A

Integral membrane proteins (embedded within; can’t be easily removed from bilayer without using harsh detergents that destroy it, float freely in bilayer; usually transmembrane- amphipathic)

associated membrane proteins (not directly attached; change in pH, chelating agent, urea, carbonate)

(GPI) anchor membrane proteins (phospholipase C cuts and get protein glycan)

peripheral (amphitropic) membrane proteins (easily separated from bilayer without harming it, less mobile within; biological regulation removes)

Each type of membrane has characteristic (dif composition/ concentration) lipids and proteins; and organelles also have them

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49
Q

Fluid Mosaic Model

A

Two-dimensional liquid in which phospholipid and protein molecules diffuse easily. The original model has been updated to account for membrane domains that restrict the lateral diffusion of membrane components (have special lipids and protein composition- lipid rafts; important for cell-cell signaling, apoptosis, cell division, membrane budding, and cell fusion)

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50
Q

Asymmetric Distribution of phospholipids in plasma membranes

A

lipids are associated differently from inside/outside; some cells on outside have more sphingomyelin receptors; signal transduction on inside

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51
Q

Distribution of Lipids in a typical cell

A

Golgi has different composition than trans goli network than transport vesicle (this one matches plasma membrane)

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52
Q

Transbilayer deposition of glycophorin (membrane spanning protein that carries sugar molecules ) in a RBC

A

N terminus outside and C terminus inside (most common?)

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53
Q

Integral proteins

A
Type 1 (carboxy in, amino out)
Type 2 (amino in, carboxy out)
Type 3
Type 5- transmembrane receptor/like a channel protein
Type 7- single transmembrane
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54
Q

Lipid linked membrane proteins

A

different FA that attach them ex. GPI anchor on C terminus

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55
Q

Membrane Dynamics

A

2 extremes of lipid bilayer: liquid ordered state and liquid disorder state (heat produces thermal motion of side chains)

saturated need more energy to melt (increase melting point= S–>L) as well as longer length [dictate how membrane behave- fluidity]

In order to survive in low temp, need more oleic acid (18:1) than palmitric acid (16:0) to keep membrane fluid

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56
Q

Transbilayer movements require catalysis

A

Uncatalyzed transbilayer (flip flop diffusion)- very slow
Uncatalyzed lateral diffusion (very fast)
Catalyzed transbilayer translocation (ATP)- Flippase (p type ATPase, moves Pe and Ps from outer to cytosolic leaflet), Floppase(ABC transporter, moves phospholipid from cytosolic to outer leaflet)
Scramblase (moves lipids in either direction, toward equilibrium)

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57
Q

Movement of Proteins across membrane

A

plasma membrane is supported by cytoskeleton- assembly/disassembly during fusion

React cell with fluorescent probe to label lipids–> intense laser beam bleaches small area –>with time unbleached phospholipid diffuses into bleached area which shows lipids move in membrane

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58
Q

Membrane Microdomains

A

Lipid rafts are specialized membrane microdomains that compartmentalize cellular processes by serving as organizing centers for the assembly of signaling molecules, influencing membrane fluidity, and membrane protein trafficking, and regulating NT and receptor trafficking

Caveolins are a family of integral membrane proteins that are principal components of caveolar membranes and involved in receptor independent endocytosis. Act as a scaffolding (support) protein within caveolar membrane by compartmentalizing and concentrating signaling molecules; various classes of signaling molecules, including G- protein subunits, receptor and nonreceptor tyrosine kinases, endothelial nitric oxide synthase and small GTPases, bind Cav-1 through its ‘Caveolin scaffolding domain’

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59
Q

Solute Transport Across the Membrane

A

Simple Diffusion-nonpolar compounds only, down concentration gradient (passive)

Facilitated Diffusion- down EC gradient (passive)

Primary active transport- against EC gradient diven by ATP ex. Na/K ATPase

Secondary active transport- against EC, driven by ions moving down its gradient

Ion channel- down EC gradient, may be gated by ligand or ion (passive)

Ionphore- mediated ion transport down EC gradient

Simple diffusion without transporter requires more free energy than diffusion with transporter

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60
Q

CO2 in respiring tissues

A

CO2 produced by catabolism enters RBC–> Bicarbonate dissolves in blood plasma through chloride (goes in)- bicarbonate exchange (goes out)

CO2+ H20–> HCO3- H+ Cl- (carbonic anhydrase)

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61
Q

CO2 in respiring lungs

A

Bicarbonate enters RBC from blood plasma through
chloride (goes out)- bicarbonate exchange (goes in)–> CO2 leaves RBC and is exhaled

HCO3- H+ Cl- –>CO2+ H20 (carbonic anhydrase)

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62
Q

Types of transporters

A

Uniport

Cotransporters (Symport [same direction] or antiport [opposite direction])

ex. On apical membrane (facing intestinal lumen) have microvilli with 2 Na/1 Glucose symporter (drivent by high extracellular Na

On basal surface (facing blood) have 3Na (out)/ 2K (in) ATPase antiport AND have Glucose uniporter GLUT 2 (facilitates downhill efflux)

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63
Q

Membrane Fusion Events

A

Budding of vesicles from Golgi, exocytosis, endocytosis, fusion of endosome and lysosome, viral infection, fusion of sperm and egg, fusion of small vacuoles (plants), separation of 2 plasma membranes at cell division

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64
Q

Nervous System Overview

A

CNS (brain and spinal cord)

PNS (Cranial nerves and spinal nerves)–> somatic (voluntary; conscious) OR ANS (involuntary, subconscious)–> Sympathetic/ Parasympathetic

Neuron cell bodies receive input from dendrites, they send info via axons to other neurons or to target organs, axons degenerate due to damage and injury but can regenerate in the periphery, cell bodies last to die in injury and disease and rarely replaced in CNS

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65
Q

Spinal Cord Function

A

Relays info to and from brain, has local circuits (reflexes) and preserves segmental body plan (trunk/abdomen)

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66
Q

Spinal Cord Location

A

rostral extent- emerges from foramen magnum (hole in base of skull through which spinal cord passes)

caudal extent- ends between L1 and L2 vertebrae

In the developing fetus, L5 spinal cord and L5 nerve root location different because vertebral elements grow faster and further than spinal cord and nerve is dragged down with it (intervertebral foramen) - L5 spinal cord level is ABOVE L5 vertebrae, specifically around T12 /L1 level; cauda equina is around L5 vertebrae/nerve root

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67
Q

Vertebrae

A

Segmental organization of the vertebral column, vertebrae protect the spinal cord and support the body, spinal nerves emerge directly below their corresponding vertebrae, with one exception (don’t worry about coccygeal vertebrae)

C1-7 (transverse foramen), T1-12 (costal facets, spinous process protrudes down), L1-5 (huge body), S1-5 (all fused)

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68
Q

Spinal Cord Organization

A

segmental organization
7 cervical vertebrae, 8 cervical spinal levels, 8 spinal nerves; first spinal nerve emerges above C1 vertebrae, C8 nerve emerges below C7

12 thoracic vertebrae, spinal levels, and thoracic spinal nerves (nerve always emerges below vertebrae) [spinal cord located between T1 and T11 vertebrae)

5 lumbar vertebrae, spinal levels, spinal nerves (nerve always emerges below vertebrae) [spinal cord located between T11 and L1 vertebrae) Different growth IS NOW APPARENT

5 fused Sacral vertebrae, spinal levels, Spinal nerves (nerve always emerges below vertebrae) [spinal cord is located between L1 and L2 vertebrae]

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69
Q

Meninges- 3 CT layers

A

Dura mater (outermost layer, under bone, dense/tough)

Archanoid mater(middle layer, has blood vessels going through, thin; has subarchanoid space which holds CSF)

Pia mater- dentate ligaments (help spinals to sides)

70
Q

Gray matter

A

Has cell bodies

Dorsal horn (sensory neurons- somatic and visceral; secondary sensory neurons)

Lateral horn (motor neurons- visceral)

Ventral horn (motor neurons- somatic)

  1. Thoracic grey matter smaller (not as many neurons in this region because not alot of motor action in trunk; cervical and lumbosacral enlargement)
  2. The colors are reversed on schematic (many stains coat myelin, so white matter is often darker in stained sections)
  3. There is a lot more white matter in the cervical regions (more axons close to CNS ; as get closer to brain, more traffic)
71
Q

White matter

A

myelinated axons; ascending neuronal axons (pain, temp, touch) and descending neuronal axons (pathways for muscle)

Pathway for sensory info from each segmental level to brain, motor information from brain to segmental levels

72
Q

Spinal Nerves

A

Roots- dorsal (has ganglia) and ventral
Trunk- very short
Rami- Dorsal and ventral

73
Q

Roots

A

One way streets

Sensory (dorsal) info towards the spinal cord [AFFERENT]

Motor (ventral) info towards the periphery [EFFERENT]

**Dorsal root ganglia helps with orientation

74
Q

Trunk and Rami

A

2 way traffic
Rami- sensory and motor info

Dorsal rami- shorter one, serve DEEP back muscles and skin on back

Ventral rami- serve body wall and limbs

  • cervical plexus (neck/head)
  • brachial plexus (shoulder/upper limbs)
  • intercostals (easy, segmental body plan, serves trunk)
  • lumbar and sacral plexi (groin and lower limbs)
75
Q

Dermatomes

A

regions of skin that correspond to a given spinal cord level (sensory)

C2-occipital proterbance
C4-collar [spinal cord/nerve level around collar]
C5- shoulder 
C6- thumb
C7- middle finger
C8- pinky
T1- medial elbow [spinal cord/nerve level around first rib]
T4-nipple (teat pore)
T7-xiphoid process
T10- umbilicus (belly button)
76
Q

Myotomes

A

Muscles that correspond to a given spinal cord level (movements)

C5-shoulder abduction
C6- elbow flexion, wrist extension
C7- elbow extension

77
Q

Autonomic Nervous System

A

Sympathetic: fight or flight (smooth muscle of vessels)

Parasympathetic: rest and digest (smooth muscle of digestive system/ visceral organs)

78
Q

ANS 2 neuron pathway

A

CNS [preganglionic neuron]–> autonomic ganglion [post ganglionic neuron]–> target organ

Basis for both S/PS

79
Q

Preganglionic Sympathetics

A

ORIGINATE: T1-L2 spinal cord levels

Preganglionic sympathetics- sympathetic innervation of pupil, heart, bronchial tree, hepatic artery, adrenal medulla, genitals, or sweat glands

80
Q

Preganglionic Parasympathetic

A

ORIGINATE: Brainstem (cranial nerves 3, 7, 9, 10) or S2-4 spinal cord levels

Preganglionic parasympathetics- parasympathetic innervation of the pupil, heart, bronchial tree, stomach, genitals, or bladder

Brainstem- everything except what S2-4 levels innervate
S2-4- hindgut (descending colon to anus), pelvic organs and perinuem

81
Q

Post ganglionic neurons embryo story

A

X section through developing embryo: neural tube, neural crest cells [face; other tissues, BECOME PERIPHERAL NERVE GANGLIA in PNS], somites [muscles], notochord (intervertebral disc, vertebrae body) Dorsal aorta, IVC, gut tube

82
Q

Neural Crest Cells

A

BECOME PERIPHERAL NERVE GANGLIA in PNS
1. Dorsal root ganglia (sensory neurons- somatic and visceral)

NC cell migration
2. In front of notochord
SYMPATHETIC CHAIN with sympathetic ganglia
(Paravertebral ganglia) ; postganglionic sympathetic neurons ; Blood vessels or sweat glands

NC cell migration
3. In front of aorta
PREAORTIC GANGLIA (prevertebral ganglia); postganglionic sympathetic neurons;

NC cell migration
4. Into the viscera
INTRAMURAL GANGLIA
postganglionic parasympathetic neurons; embedded in tissues/target organs

83
Q

Sympathetic pathways

A

Sympathetic ganglion, sympathetic internodal fiber, sympathetic chain,

white ramus communicans (PREGANGLIONIC SYMPATHETICS TRAVELING THE SPINAL CORD AND THE CHAIN),

grey ramus communicans (PRE AND POSTGANGLIONIC SYMPATHETICS TRAVELING TO THE PERIPHERY),

splanchnic nerve (PREGANGLIONIC SYMPATHETICS TRAVELING TO PREAORTIC GANGLIA, INNERVATES GI TRACT)

preaortic ganglion

GO TO APPROPRIATE LEVEL TO SYNAPSE

84
Q

Connective Tissue

A

Loose CT, Dense CT (regular, irregular), Cartilage (hyaline, fibrocartilage, elastic) bone, blood

85
Q

Cartilage

A

Composed of cells (CHONDROCYTES) embedded in jelly-like matrix of ground substance containing various fibrous molecules

STRUCTURALLY DESIGNED TO : withstand tension/compression, provides low friction surface at joints, provide support for soft tissue, provide a framework for long bone osteogenesis (during development)

skeleton initially made of cartilage/fibrous membrane- mostly replaced by bone
- chondroblasts produce new collagen matrix until skeleton stops growing; the few cartilages that remain in adults are found mainly in regions where FLEXIBLE CT is needed

DIFFER FROM BONE:
More flexible, avascular (less blood supply, thus heals very slowly), less organized structure, no nerve fibers, composed of up to 80% water

Nutrients come via diffusion through PERICHONDRIUM
(FIBROUS CT SHEATH; surrounds cartilage and acts like a girdle to resist outward expansion when compressed and CONTAINS: Type 1 collagen (denser, provides structural strength), vascular supply to cartilage, chondrogenic cells (capable of differentiating into chondroblasts [immature] and chondrocytes [mature), not present in all types of cartilage

86
Q

Cartilage of the human skeleton

A
  1. Hyaline 2. Fibrous 3. Elastic

Have same basic structure but differ in cell distribution and/or number, and the type of fibers in the matrix

87
Q

Components of Cartilage

A

CELLS (Immature are chondroblasts which secrete ground substance matrix/fibers and mature are chondrocytes which are less active and enclosed in lacunae)

FIBERS (provide structural support ex:

  • Collagen: strongest (even than steel), thin fibers:Hyaline (finer Type 2 only) , thick fibers:fibrocartilage (Type 1 & 2)
  • Elastic: gives tissue elasticity ex: elastic c.(elastic fibers + Type 2)

GROUND SUBSTANCE: gel like interstitial fluid filling the space between cells; composed of water, glycosaminoglycans, proteoglycans [aggregates of CHONDROITIN SULFATE +hyaluronic acid] , and glycoproteins; The tightly packed and highly charged proteoglycan sulfate groups generate electrostatic repulsion that provides much of the resistance to compression. loss of chondroitin sulfate in cartilage is a major cause of OSTEOARTHRITIS

88
Q

Proteoglycan Repulsion

A

Cartilage is composed of cross linked type II collagen fibers bond to proteoglycan aggregates made up of chondroitin sulfate (forming glycosaminoglycan molecules) linked to hyaluronic acid

Proteoglycan consists of a protein core with one or more negatively charged covalently attached glycosaminoglycan chains

PROTEOGLYCAN REPULSIONS OCCURS BETWEEN ADJACENT NEGATIVELY FIXED CHARGES OF ADJACENT GLYCOSAMINOGLYCAN MOLECULES

89
Q

Hyaline Cartilage ***

A

MOST widespread type of collagen, ABSORBS mild compression, provides SUPPORT, FLEXIBILITY & RESILIENCE. WEAKEST of the 3, resembles frosted glass;

COMPOSITION: has perichondrium, spherical chondrocytes, Type 2 collagen fibers, and no nerves or blood vessels

LOCATION: Articular cartilages (end of most long bones at movable joints), costal cartilages (rib to sternum connection), respiratory cartilages (skeleton of larynx, reinforce respiratory passageway and tracheal rings), and nasal cartilages (support external nose)

In embryo, bone begins as hyaline- ossification occurs as chondroblasts die and replaced by osteoblasts clustered in OSSIFICATION CENTERS. bone formation proceeds from these centers

90
Q

Fibrocartilage **

A

STRONGEST; alternating parallel layers, matrix has ROWS OF CHONDROCYTES, THICK COLLAGEN FIBERS oriented in direction of functional stress

only type that has BOTH Type 1 & 2 collagen fibers (more fibers, fewer cells than others); only type that LACKS perichondrium (SLOWEST to heal)

HIGHLY COMPRESSIBLE- great tensile strength, able to withstand high pressure and high stretch sites

LOCATION: menisci of knee, intervertebral disc, pubic symphysis

91
Q

Elastic Cartilage **

A

resembles hyaline but MORE SPRINGY (intermediate), able to stand up to repeated bending

Has PERICHONDRIUM, chondrocytes are in a threadlike network of ELASTIC FIBERS and Type 2 collagen fibers within the matrix (provides strength, elasticity, and maintains shape)

LOCATION: external ear, epiglottis (covers larynx during swallowing)

92
Q

Axial vs Appendicular

A

Axial- the central axis- skull, ribs, vertebral column, sternum

Appendicular- limbs and girdles (pelvic and pectoral)

93
Q

Functions of Bone **

A
SUPPORT (structural framework for body, attachment for muscles)
PROTECTION (of internal organs)
ASSISTING MOVEMENT (musculoskeletal system)
MINERAL HOMEOSTASIS (store of Ca and Pi)
BLOOD CELL PRODUCTION (hematopoesis in bone marrow)
94
Q

Bone vs Cartilage

A

Both have living cells which occupy lacunae
- Bone (osteocytes) cartilage (chondrocytes)
Both have fibrous CT covering
-bone (periosteum) cartilage(perichondrium)
Bone is HIGH VASCULARIZED unlike cartilage
Bone intracellular matrix has MORE COLLAGEN than cartilage (greater tensile strength, more than steel) heavily MINERALIZED with Ca salts, osteocytes UNABLE DIVIDE hence all bone growth is by APPOSITION (deposition of bone on preexisting surfaces)

95
Q

Adult bone structure **

A

All adult bone is composed of LAMELLAE (layers of mineralized bone matrix that make up mature bone)
they are arranged to for 2 structures:
- COMPACT (cortical) bone- makes outer layer of most bones (regular pattern) ~80% of bone in body
-TRABECULAR (spongy) bone- inside compact (irregular pattern) ~20% of bone in body

Lamellae make osteon with central (Haversian canal) and canaliculi are channels that link lacunae

Protein in bone matrix is over 90% type I collagen, which is also major structural protein in tendons and skin (weight by weight as strong as steel)

96
Q

Bone remodeling **

A

Throughout life bone is constantly being turned, resorbed, and new bone formed

REMODELING STAGES:

  1. bone resorption (breakdown) by osteoclasts (erode and absorb bone)
  2. bone formation b osteoblasts (modified fibroblasts that lay Type i collagen and form new bone matrix (osteoid) at or near where osteoclasts resorbed it

Osteocytes are mature bone cells (from osteoblasts maturing and being surrounded by bone matrix)

97
Q

Osteoclasts

A

Multinucleated cells; Attach to bone via integrins at isolated areas called SEALING ZONES; H dependent ATPases then move from endosomes and acidify the compartment to ~pH 4; the acidic pH dissolves HYDROXYAPATITE and collagen, forming a shallow depression in bone (release of Ca/Pi in blood); the digested products are endocytosed and move across osteoclast by transcytosis, with release into interstitial fluid

98
Q

Hormonal Regulation of Remodeling

A

Parathyroid hormone (PTH) and 1,25 (OH)2 VIt D (activated form) both promote healthy remodeling and maintain bone homeostasis

Direct effects on osteoblasts and osteoclasts (rapid)

indirect effect on osteoid accumulation on osteoclasts is slower (stimulate expression of RANK ligand receptor to activate osteoclasts)

99
Q

Ca and Phosphate Homeostasis Importance **

A

Homeostasis is a property of an organism or system to maintain its parameters within a normal range of values

Ca is a vital 2nd messenger needed for blood coagulation, muscle contraction and nerve function (if too low- cardiac condition- hypocalcemic tentany)

Phosphate homeostasis is also critical to normal body function: part of ATP, biological buffer, protein regulation via phosphorylation and dephosphorylation

100
Q

Bone Ca Homeostasis**

A

Humans contain~ 1100 g (27.5 mol) of Ca about which 99% is stored in bones

Bone is available from 2 reservoir: bone and ECG or glomerular filtrate?

Vast majority of bone Ca is in a stable reservoir that only slowly exchanges with the ECF (accretion/ reabsorbtion)

101
Q

Phosphorous Homeostasis

A

Bone contains 85% of the total body phosphorus

The kidney is the main regulator of the human phosphate homeostasis

102
Q

Hormones that regulate Ca Homeostasis **

A

PARATHYROID HORMONE (PTH)- secreted by CHIEF CELLS of the PARATHYROID GLANDS- mobilize Ca from bone, increases urinary phosphate excretion

1,25 DIHYDROXYCHOLECALCIFEROL is a steroid hormone formed from VIT D IN SKIN (SUN) and successive hydroxylation in the LIVER AND KIDNEYS- INCREASES Ca absorption from the intestine, INCREASES Ca in bone

CALCITONIN, a Ca lowering hormone secreted by the PARAFOLLICULAR CELLS (C- cells) in the THYROID GLAND- inhibits bone resportion (chewing up of bone by osteoclasts)

103
Q

Hormonal regulation of Ca Homeostasis

A

PTH and Calcitonin interact to maintain Ca levels within a narrow range:

PTH increases blood levels of Ca when plasma levels are too low

Calcitonin decreases blood levels of Ca when plasma levels get too high

Regulatory feedback between Vit D and PTH: PTH helps activate Vit D to 1,25 dihydroxycholecalciferol in kidney which can then downregulate PTH release

When Ca is TOO HIGH in plasma, Calcitonin is secreted from parafollicular cells of thyroid to inhibit Ca resorption from bone (inhibits osteoclastic break up)

When Ca decreases in the blood, PTH is secreted by parathyroid and stimulates Ca release from bone into blood, Ca reabsorption in kidney, and activation of Vit D, which further increases Ca reuptake in the intestine, to turn off PTH

104
Q

Sources of VIt D

A

Vit D is a group of closely related sterols produced by the action of UV from the sun on certain provitamins

Can be found in small amounts in fatty fish (herring, mackerel, sardines, and tuna) added to dairy products, juices and cereals

Most vit D (~90% of what body gets) is obtained through exposure to sunlight

1,25 DIHYDROXYCHOLECALCIFEROL aka Calcitriol ACTIVE FORM

105
Q

PTH Effects

A

Increases bone resorption (chewing of bone) and mobilizes Ca to plasma

Increases reabsorption of Ca in the kidney and phosphate excretion in the urine (increasing plasma Ca while lowering plasma phosphate levels; PTH strongly inhibits the transporter mediated reabsorption of Pi in the proximal tubules of kidney)

Increases plasma 1,25 dihydroxycholecalciferol levels, which in turn increases gut Ca absorption. ( Calcitriol [activated vit D] then feedback inhibits PTH release)

106
Q

Calcitonin

A

Secreted by PARAFOLLICULAR CELLS OF THE THYROID

G protein coupled receptors for calcitonin are found in both bones (on osteoclasts) and in the kidneys.

Calcitonin LOWERS Ca levels (opposing effects of PTH): Inhibits Ca absorption in intestines, inhibits osteoclast activity in bones, stimulates osteoblastic activity in bones, inhibits renal tubular cell reabsorption of Ca allowing it to be excreted in the urine

May be used therapeutically for treatment of hypercalcemia or osteoporosis (anti- resorptive meds) thus lowering risk of breaking bones

107
Q

Other hormones that impact Ca metabolism

A

GLUCOCORTICOIDS (steriods like prednisone)- weaken bones/lower plasma Ca levels by inhibiting osteoclast formation and activity

GROWTH HORMONE- increases Ca excretion in the urine, but also increases intestinal absorption of Ca, and this effect may be greater than the effect on excretion, with a resultant positive Ca balance (indirectly stimulates protein synthesis in bone)

ESTROGEN- prevents osteoporosis by inhibiting the stimulatory effects of cytokines on osteoclasts. Also prevents osteoblast apoptosis by blocking osteoblast’s synthesis of interleukin 6 and antagonizing the interleukin 6 receptors.

INSULIN- increases bone formation, and there is significant bone loss in untreated diabetes.

108
Q

Bone disease **

A

Rickets (kids) or Osteomalacia (adults)-Defective bone matrix calcification due to Vit D and/or Ca deficiency
In children this results in weakness and bowing of weight-bearing bones, dental defects and hypocalcemia.
In adults, symptoms include muscle weakness and achy bone pain. (Enamel hypoplasia and incomplete mineralization of teeth on dental exam)
Treatment for osteomalacia involves replenishing low levels of vitamin D and calcium and treating any underlying disorders that may be causing the deficiencies.

Osteopetrosis- Osteoclasts are defective and unable to resorb bone so osteoblasts operate unopposed
Bone density increases and growth becomes distorted (bulbous) with few foramina for nerves to pass through

Osteoperosis- Relative excess of osteoclast function results in loss of bone matrix and high risk of bone fractures
Involutional osteoporosis- as age increases, bone loss increases. Increased dietary intake of Ca and exercise may slow progression
Treatment: Bisphosphonate (alendronate or Fosamax) inhibit osteoclasts, preventing resorbtion and increasing mineral content of bone

109
Q

Bisphosphonate Therapy

A

For osteopetrosis
Bisphosphonate Therapy Associated Osteonecrosis of Jaw (ONJ)- disfiguring jaw condition that includes serious infection and osteopetrosis, an abnormal build up of fragile bone.

Preventative Care Prior to bisphosphonate initiation:
Patients already receiving bisphosphonates should:

110
Q

Electrical Signaling

A

Benefits: Covers long distances with minimal loss of signal, rapid, quickly repeated, information can be conveyed in patterns

Limitations: Binary (all or none), difficulty to modify, energy intensive ( a lot of movement of ions/ concentration gradients), microenvironment dependent

111
Q

Resting Membrane Potential **

A

The potential energy in the electrical gradient formed across the plasma membrane

Basis for neuron electrical activity
Formed by opposition between concentration (move out) electrical gradients (move in)
Separation of charge across the membrane (-) internal membrane (+) external membrane
caused by: 1. formation of a K concentration gradient (high inside cell and low outside cell) 2. Permeability of the membrane to K (forms an electrical gradient by moving out, negative charge inside and positive charge outside)
Presence of different ions increase/decrease the resting membrane potential
Necessary for the AP to occur

112
Q

Ohm’s Law

A

V=IR
V=voltage= potential difference between 2 points [plasma membrane- capacitor]
I= Current= flow of electrical energy between 2 points
R= Resistance- opposition to the flow of electrical energy [ex. ion channels]

we create electrical energy by slow movement of K and separates pos. and neg. charge; potential can be changed

113
Q

Diffusion drives EC equilibrium

A

When the concentration and electrical gradients for an ion are in balance

When concentrations are equal, no net flux of K, no potential energy in system

When concentration on inside is increased, Net flow of K from inside to outside

At electrochemical equilibrium, there is not an electrical potential separation of charge; Flux of K from inside to outside is balanced by the opposing membrane potential V=-58mV

114
Q

Ion transporters and channels maintain resting membrane potential

A

active transporters- actively move selected ions against concentration gradient, create ion concentration gradients Ex Na/K ATPase- establishes Na and K gradients across neuron membrane (uses ATP) moves Na out of neuron and K in, moving against concentration gradients

Ion channels- allow ions to diffuse down their concentration gradient; are selectively permeable to certain ions ex. K, Na, Ca, Cl channels; open and close due to different stimuli

115
Q

The Neuron Membrane at Rest

A

Interior of neuron is negatively charged, the separation and slow flow of K ions across the plasma membrane creates membrane potential (more neg. inside and more pos, ions outside) , Na/K ATPase activity maintains electrochemical gradients, other ions influence membrane potential

Membrane potentials allow neurons electrical activity; separation of ions needed to have an energy store (charge buildup)

116
Q

Nernst Equation

A

Calculate Membrane potential; equilibrium potential of an individual ion

117
Q

Goldman Equation

A

Calculate membrane potential; equilibrium potential of the entire plasma membrane

118
Q

The Neuron Passive Electrical State

A

Cytoplasm is electrically resistant; Neurons electrically inert at rest, passive current rapidly decays over space and time, active current flow allows neuron electrical information transfer

119
Q

Passive Current Flow

A

Current decays, cytoplasmic resistance (to the ions), relative to distance

Actually occurs: axons without channels and cell bodies

120
Q

Active Current Flow

A

Current constant over time, current repropagated, active process, relative to distance

Actually occurs: axons

121
Q

The Action Potential Overview

A
Rapid change in membrane potential (from negative to positive, then back to negative), caused by the sequential opening of Na and K channels in a voltage and time dependent manner; 
requires Na (high outside) and K (high inside) gradients
This is the electrical event that carries information throughout neurons and the nervous system
122
Q

Ion Channels create dynamic potentials

A

Passive movement along concentration gradients

  1. Leakage- small tunnel/pores; establish resting membrane potential; constant ion flow along a gradient
  2. Voltage gated- respond to changes in membrane potential (allow AP to occur)
  3. Ligand Gated- Respond to ligand binding (create a conformational change in channel structure and opens so ions can move) ex. Neurotransmitters, proteins, ions, lipids
  4. Physically Gated- Respond to other physical stimuli(moving or stretching of membrane) Mechanical, temperature, light
123
Q

Transporters create dynamic potentials

A

Active movement of ions and proteins against concentration gradients

  1. ATPase Pumps- use ATP to move one or more substrates
  2. Ion Exchangers- Energy from moving one or more ion(s) along a concentration gradient moves other ion(s) against a gradient, opposite ion direction
  3. Co- transporters- One or more ions moves another ion (one aong and one against), same direction
  4. Multiple Transporter Systems- multiple transporters working together to move a substrate
124
Q

Voltage Gated Ion Channel

A

Physical conformation changes with membrane polarization; time and charge dependent, ions move along their gradients, passive, refractory period (channel closed and can’t open again until changes conformational state)

ex. voltage gated K channel- as internal membrane becomes more pos. changes conformational structure of transporter and allows flow of K

125
Q

Ligand Gated Ion Channel

A

Ligand binding changes the conformation to allow ion movement; diversity of ligand (neurotransmitter, ions, proteins, intracellular signaling proteins, lipids) ions move along concentration gradients, passive, open in presence of sufficient ligand and appropriate environmental state

126
Q

Na/K ATPase pumps

A
  1. Na binding inside of cell 2. Phosphorylation 3. Conformational change causes Na release and K binding outside of cell 4. Dephosphorylation- induced conformational change leads to K release into cell
127
Q

The action potential **

A

NEGATIVE RESTING POTENTIAL

potential changes and once reaches threshold–> depolarization (from negative to very positive) then reverts itself (positive –> more negative than originally) –> goes back to original negative

ex. electrical activity changes state of presynaptic neuron–> release of NT–> carry info to target

  1. Resting Phase (a lot of K in, and a lot of Na out) K moving toward electrochemical equilibrium through LEAKAGE K CHANNELS
  2. Activation Phase (stimulus induced (gated) Na channels open and flow into cell which is negative)
    3 Rising Phase- more Na in and hit threshold potential–> voltage gated ion channels open and massive amount of Na flows in (external becomes negative and internal positive) [OVERSHOOT} K voltage gated channels begin to open
  3. Falling Phase- Voltage gated Na channels close and Voltage gated K channels open (moving along concentration gradient) leave negative inside, K moves toward equilibrium potential (leakage also still open)
  4. Undershoot phase- Refractory period where voltage gated Na channels can’t open and where K voltage gated K channels close [can’t have another AP]
  5. Recovery Phase- Na/K ATPase re-establishes membrane potential and Leak K Channels help re-establish resting potential
128
Q

AP vary across Species

A

Same general shape, but vary in size, width etc.

129
Q

AP are initiated at axon hillock (trigger zone)

A

Where the axon meets the cell body; Na voltage gated channel dense region, relatively low membrane threshold, postsynaptic membrane potentials are summated

AP in cell body are passive–> currents get added up (if pass threshold, create AP)

130
Q

Axonal Conduction of an AP

A

Anterograde (toward presynaptic terminal); undirection

131
Q

Increasing AP Conductance

A
  1. Increase Axon Caliber
    - reduce internal resistance, energy intensive, physically restrictive
  2. Insulate axon- prevent current leakage, requires glial support, oligodendrocytes (CNS) and Schwann cells (PNS)
132
Q

Saltatory Conduction speeds AP velocity

A

due to myelination; electrical signal moves rapidly by jumping between myelination; Node of Ranvier (concentration of Na channels)

unmyelinated= 0.5-10m/s
myelinated= 150 m/s

demyelination- causes MS, stress, oxidative stress, neurons not set up to deal with energy expenditure, and slower signal

133
Q

Neurons Communicate at Synapses to form networks

A

connect to target tissue; AP must be converted to a chemical signal (Nt or neuropeptide)
NS collects info–> sends to CNS–> processing, execution –> AP–> chemical signal at synapse

134
Q

Chemical Synapse Structure

A

Axon, synaptic vesicle pool, Active zone, in presynaptic terminal–> synapse–> postsynaptic terminal

benefit of not being continuous: point where you can modify signal

135
Q

Neurotransmitter

A

Small molecules

  • aa or derivatives, synthesized in the presynaptic terminal, stored in small (clear) synaptic vesicles ( ~40-60nm in size ), released from the presynaptic terminal; cross synapse
    ex. Glutamate (primary excitatory NS), GABA (primary inhibitor NS), ACh (sympathetic NS), Serotonin, Glycine, Norepi, Dopamine, Histamine, Epi

neuropeptides
- proteins (or small peptide chains), synthesized in the cell body, stored in large (dense core) vesicles ~80-150nm in size; released both pre- and post-synaptically, can be released into extracellular environment (affect multiple cells)

136
Q

Synaptic Transmission Overview **

A
  1. AP
  2. Ca2+ depolarization
  3. Ca2+ influx (messenger)
  4. Synaptic vesicle fusion
  5. NT release into synaptic cleft
  6. NT receptor activation (post and presynaptically)
  7. NT reuptake (by adjacent glial cells or neurons)
  8. NT sequestration (put back into synaptic vesicle)/ metabolism (broken up)
137
Q

AP cause presynpatic Ca Influx

A

AP depolarize the presynaptic membrane (becomes positive), Voltage gated Ca channels open, increase intracellular Ca drives vesicle release

In absence of AP, voltage gated channels can be opened by ligand

138
Q

Synaptic Vesicle Resides in 3 Distinct pools

A
  1. Readily releasable pool 2. Recycling pool 3. Reserve pool

Classic model- physical segregation into 3 different pools; active zone (dense in proteins that will pull vesicles to membrane) as pools depleted, reservoir pool

Current model- some vesicles free to move and others are not; set of stages of release as above so we don’t run out

Every neuron in our body is constantly firing at some degree using it in different ways

139
Q

SNARE Complex Proteins allow vesicle release

A

Synpatic vesicles can tether to SNARE, SNAP 25 binds to both Syntaxin on presynaptic plasma membrane and Synaptobrevin on synaptic vesicle membrane

Botox causes change- cleaves SNARE proteins

140
Q

Neurotransmitter Release **

A
  1. vesicle docks
  2. SNARE Complexes form to pull membrane together (Synaptobrevin, Syntaxin, SNAP 25)
  3. Entering Ca2+ binds to synaptotagmin
  4. Ca2+ bound synaptotagmin catalyzes membrane fusion by binding to SNAREs and the plasma membrane
  5. release of NT
141
Q

Models of Membrane Reuptake and Vesicle Reformation

A

Membrane needs to be pulled off to retain size

Classic Synaptic Vesicle Cycle: Endosome–> budding–> Docking–> priming–> fusion (Ca- 1 ms)–> exocytosis (1 min)–> endocytosis (10-20s)–> budding–> endosome

Ultrafast Synaptic Vesicle Cycle [more likely]has to cycle or won't work 
Ultrafast endocytosis (100ms)--> large endocytic vesicle--> synaptic endosome (1 s) --> clathrin coat (3 s)--> synaptic vesicles (5s)--> exocytosis
142
Q

Neurotransmitter Receptor Type

A

Ionotropic (ligand gated ion channels)

Metabotropic (G protein coupled receptor) can affect ionic conduction not just moving ion

143
Q

Ionotropic NT receptor

A

ligand binding opens ion channel, variable selectively for ions, not necessarily unidirectional, directly involved in creating post synaptic electrical current and changing membrane potential, excitatory (depolarizing- Na) or inhibitory (hyperpolarizing (Cl)

FAST (ms)

144
Q

Metabotropic NT Receptor

A

G protein coupled intracellular signals, relatively slow activation time (s), prolonged signal duration, signals modify the activity of ionotropic receptors, ion channels and transporters; signals alter terminal structure and function

145
Q

NT receptor change postsynpatic membrane potential

A

Excitatory Postsynaptic Potential (EPSP)- Depolarization of the postsynaptic membrane through its own cell body ex. Na, Ca

Inhibitory Postsynaptic potential (IPSP)- Hyperpolarization of postsynaptic membrane
ex. influx of Cl, efflux of K

146
Q

Location influences Synaptic Input strength

A

Synapse Location matters; membrane potentials decay, proximity to the trigger zone dictates the relative influence of a synaptic input, decay over space/time

147
Q

Postsynaptic Potential Summation

A

Summation- the total change in membrane potential based on the spatial (location) and temporal (frequency) aggregation of postsynaptic potentials

Sufficient depolarization triggers an AP, axon hillock

signals are summed; pass threshold–> AP (axon)–> second neuron
Inhibitory signal can play a role (subtracted)–> smaller signal that prevent firing to reach axon hillock

148
Q

Neurons create complex networks

A

Neurons organize complex networks and form discrete structures; networks are established early in life, information processing is dictated by network connectivity, brain structure have vast, but specific connectivity, Within structural confines, networks are highly plastic (malleable- can be shaped, changed) throughout life

Cerebral cortex is a large network that gives rise to discrete brain structures that perform function but ALL connected to each other; conductivity is pretty conserved (connections) but broad range of variability in plasticity

149
Q

Networks acquire information, process information and execute behaviors

A

Afferent (internal and external environment)–> sensory receptors, sensory ganglia and nerves –> Brain (analysis and integration of sensory and motor information)–> Visceral (autonomic ganglia and nerves) and Somatic motor systems (motor nerves) –> effectors

150
Q

Neuronal Networks map external and internal environments in the brain **

A

All senses are mapped to discrete regions of the cortex (ex. somatosensory cortex), emotional and abstract (short term memory, emotions, thoughts) states are mapped in deep brain areas, maps are overlaid and compared in association cortices

Senses are segregated but are dependent and interact with each other which leads to decision making and behaviors

151
Q

Simple Networks can perform simple behaviors **

A

Spinal reflexes- sensory and motor loops that function independent of descending brain control

NS is not a summation of reflexes;
descending control (brain has a lot of impact on how these reflexes occur- modified in context of environment);
measure of network health and connectivity (if damage, will not see these reflexes)
Many oral reflexes ex gag reflex

Reflex protect muscles and prevent excessive pulling; can induce this

152
Q

Hebbian Theory

A

Networks change
Neuronal networks undergo activity-dependent plasticity throughout life
Activity drives neural network consolidation, while inactivity leads to decay

Synapse pruning occurs during development (also adult pruning- selecting only important connections- critical period)
Long term potentiation (increase) (LTP) and Long term depression (decrease) (LTD) occur during adulthood: strengthening of connections, number of connections, In depression, inefficiency in info transfer, reduction in connection, higher threshold needed to be passed within network to be passed on to target

153
Q

Changes at Synaptic Terminals drive neuronal plasticity

A

The NS is constantly changing in response to activity and inactivity- whatever you spend your time doing, you will get better at

Increased/decreased synaptic vesicle release, increased/decreased receptor density, changes in receptor sensitivity and conductance, changes in receptor subtype expression, sprouting of new synapses, formation of new connections

ex. muscle memory

154
Q

Touch: The basic somatosensory circuit **

A

3 neurons communicate peripheral sensation to the brain:
1st order: mechanosensory neuron –> brainstem (medulla)
2nd order: Brainstem (medulla) –> thalamus (distribution center of brain) [DECUSSATE- cross the midline at the level of the medulla)
3rd order: Thalamus–> somatosensory cortex

Information is processed contralaterally (opposite side of where it was perceived) within brain [ info at right side of body is perceived on left side of body]

155
Q

The body is segregated into dermatomes

A

Dermatomes are cutaneous division of simal nerve innervation; organized rostrally to caudally , dermatomes overlap, varying degrees of innervation and number of sensory fields (what sit in dermatomes and send info to brain)

156
Q

Sensory field Dermatomes

A

Discrete areas of touch discrimination; sensory fields overlap, size of a field is determined by (the number of neurons innervating a dermatome, the degree of neuronal arborization) highly variable in size

more sensitive more neurons

157
Q

Physical Distortion activates mechanosensory neurons **

A

Mechanosensory neurons are pseudounipolar neurons that detect touch (dendrite to axon tree)
Plasma membrane movement opens Na channels–> electrical signal; AP NOT initiated at cell body; pain (nocioceptors) and temperature neurons (thermoreceptors) have free nerve endings- explicit receptors for particular pain
somatosensory neurons involved in touch are encapsulated by mechanoreceptor cells

158
Q

Mechanoreceptor cells encase mechanosensory nerve endings **

A
  1. Merkel cells (discs)- movement/depression of ridge
  2. Meissner Corpuscle- compression
  3. Ruffini endings- sensation of stretching of skin, sustained pressure, perception of heat
  4. Pacinian Corpuscle- vibration/pressure

Detect and transfer different types of skin distortion information, senstivity, response time, and duration of activation vary, a single neuron innervates a single mechanoreceptor cell type, nocioceptors and thermoreceptors have free nerve endings (temp/pain)

159
Q

Mechanosensation in the face and oral cavity

A

Oral dermatomes and oral somatosensation networks

mouth, head, neck innervated by cranial nerves ex. trigeminal and vagus, facial nerve
Somatosensory cortex is in brain

160
Q

The somatosensory cortex maps the body’s surface

A

Physical representation of peripheral somatosensation (mechanoreceptors, pain, temp); cortical area is dictated by the density of peripheral innervation and extent of synapse formation; Sensory information is passed along:
- secondary somatosensory cortex; associated cortices, premotor cortex (plans activity), limbic cortex ( perceive and respond to emotion) and frontal cortex ( executive function)

Homonculus- represents the number of mechanosensory neurons for certain parts of body (finger neurons have less arborization- closer together)

161
Q

Sensory fields are organized in the Somatosensory cortex

A

Very organized distribution per stimulus coming in

162
Q

The somatosensory cortex is plastic **

A

Cortical regions expand and contract in size (less stimulus for activation, sensitivity, information transfer) use increases connectivity (sensitivity) while disuse decreases connectivity

Neuronal networks are less plastic with age; network perceives world around you-map

163
Q

Pain is not a uniform signal

A
  1. Somatic- pain perceived from peripheral cutaneous perception (thermal, mechanical, chemical- what touches skin)
  2. Visceral- pain perceived from internal organ systems (referred, perceived as peripheral ex. heart attack)
  3. Neuropathic- pain caused by damage to PNS and CNS neurons is perceived as a burning or shocking pain (most of it is peripheral, brain has no pain receptors so no capacity to detect a painful stimlulus)

Pain protects us- stop use of a damaged system, consequence of damage/injury, OR not associated with disorder/infection

164
Q

Pain is perceived by nocioceptors **

A

Nociceptors- neurons with free nerve endings containing receptors that perceive a specific pain stimulus

Thermal nociceptors- temp. extremes (> 45 C or

165
Q

Pain signaling- Initiation

A

Cutaneous nociceptors activated, inflammation releases modulatory signals (prostoglandins, thromboxanes, leuotrines, neuropeptides); inflammatory molecules (drive inflammation, sensitize nociceptors [more sensitive to thermal/mechanical change] , directly activated nociceptors; Non- steroidal inflammatory drugs (NSAIDs) treat somatic pain (aspirin, IBU, acetomenophin); Block COX 1/2 activity (produce prostaglandins, thromboxanes from arachnoid acid )

166
Q

Pain signaling- afferent connections **

A

1st, 2nd and 3rd order neurons; somatosensory cortex destination, first order neurons synapse in the spinal cord, second order neurons decussate (cross) in the spinal cord; pain can be gated (affected within) at the spinal cord

visceral–> perceived by somatic nociceptors (organ referred pain)
pain/touch split which way up spinal cord- can lose perception of touch but not of pain if damage one side

167
Q

Silent Nociceptors refer pain

A

They synapse onto the same second order neurons as peripheral nociceptors ; ex. heart attack- pain on left arm

168
Q

Pain is gated at the spinal cord**

A

Gate theory of pain

Pain is gated and regulated at the level of the spinal cord (hurt knee, then hold it) ; nociceptors and second order connection
peripheral touch inhibits nociceptor, no descending (brain) signaling required, descending signals can influence spinal gating

Descending serotonin neurons activate Enkephalin-releasing interneuron–> neuropeptide–> interact with pre and post–> inhibit perception of pain [brain can send signals that inhibit perception of pain- disrupts first order to second order connection]
sensitive to opioid drugs

169
Q

Opiates

A

Interact with central pain receptors (brain and spinal cord) to block the transmission of nociceptive stimuli to the somatosensory cortex ; cause IPSP-presence of stimulus and reduces perception [plasticity exists- sensitization can occur]
increase sensitivity of terminals- more synaptic vesicles, voltage gated channels; compensation from lack of perception of pain–> when opiate removed, greater sensitivity of pain at second order neuron

170
Q

Drugs can inhibit pain peripherally and centrally**

A
NSAIDs
Prevent pain peripherally- stop nociceptors from perceiving pain, inhibit COX 1/2, reduce the production of pro-inflammatory lipids, reduce inflammation, prevent nociceptor sensitization, common drugs (Acetlysalicylic acid (Aspirin)
Ibuprofen (Advil, Midol)
Acetaminophen (Tylenol)
Naproxen (Aleve)) 

Opiates
Prevent pain centrally- ability to signal to next neuron in chain is blocked, inhibit nociceptor to second order neuron transmission, abuse potential (pleasurable aspect of reward encoded by endogenous opiates), tolerance, scheduled- most pain meds are schedule 2; 1 (high abuse potential, no therapeutic use)-5
Common drugs (Morphine (Avinza, Duramorph)
Oxycodone (Oxycontin)
Fentanyl (Duragesic, Abstral))