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Flashcards in Nervous System Deck (86):
1

The creation of peptide hormones
4 steps

mRNA binds AAs into a Preprohormone
Signal sequence removed -> inactive pro hormone
Pro hormone excreted in vesicles, enzymes cut into active peptides
Exocytosis into blood

2

Peptide hormone post translational processing
3

PreproTRH has 6 copies of active hormone
Peptide chain of insulin folds back with the help of disulphide bonds.
Pro hormone -> insulin and C peptide

3

Peptide hormone receptors

Peptide hormones are lipophillic
Binds to g coupled receptors
Activate adenylyl cyclase -> cAMP -> kinases

4

3 types of hormone interactions

Synergistic: combined is greater than individual
Permissive: one hormone required for another to work
Antagonistic: hormones have opposing effects

5

Mechanism of steroid hormones
3

Receptor hormone complex binds to DNA and activates or represses
Translation makes new proteins
Some also bind to G proteins to generate second messengers

6

Mechanism of amine hormones

Derived from modifying amino acid by modifying side groups
Catecholamines- modified tyrosine. Bind to g coupled -> exocytosis
Thyroid- 2 tyrosines and iodine. Act in nucleus. Precursors -> diffusion

7

The simple reflex of parathyroid hormone

Low plasma Ca2+ stimulates the parathyroid endocrine cell gp coupled
Parathyroid hormone released
Travels to kidney and bones
Bone and Lindsey resorption of calcium
Production of calciferol -> intestinal absorption

8

The complex reflex of the hypothalamic pituitary pathway

Anterior pituitary -> 6 hormones -> tropic hormones control other endocrine glands
Posterior-> oxytocin and ADH storage and release

9

Hypothalamic hypophyseal postal system
3

Hypothalamic neurons synthesise tropic hormones and release them into portal system capillaries
Portal vessels -> anterior pituitary
Endocrine cells release hormones into second set of capillaries for distribution to the body

10

Hypothalamic long feedback loop

Last hormone in pathway feeds back to suppress its trophic hormones

11

Hypothalamic short feedback loop

Pituitary hormones feedback to decrease secretion by hypothalamus

12

The 3 basic causes of endocrine disorders

Hormone excess- exaggerated response, gigantism, Graves' disease
Hormone deficiency- lower response, addisons, hashimotos
Defects in hormone response- altered response, hyperinsulinemia

13

Growth hormone pathway 3
Disorders 2

GHRH from hypothalamus via hyposeal capillaries
GHRH release GH from anterior pituitary, converted to IGF by liver
GHIH inhibits release from hypothalamus
Growth hormone and insulin like growth factor act on tyrosine kinases
Bone and tissue- occurs at epiphyseal plate
Increase in blood glucose and cartilage growth
Deficiency- GH/GHRH or receptors. Pituitary dwarfism
Excess- pituitary tumour, gigantism and acromegaly

14

Endocrine control of calcium balance
6

Calcium 0.9% intracellular
Calcium-phosphate crystals stored on collagen fibres
Endogenous precursors + sunlight -> vitamin D
Vitamin D -> 25-hydroxycholecalciferol in liver
-> calcitriol in the kidney, released calcium from bone
Negative feedback from high calcium levels

15

Parathyroid hormone 4
Inhibitory transmitter 2

Peptide hormone
Acts on g coupled receptors
Depolarises membrane of postsynaptic
-> excitatory postsynaptic potential and action potential

Hyperpolarises membrane
Inhibitory post synaptic potential

16

ACH metabolism
3

Choline + Acetyl CoA by cholineacetyltransferase
Degraded by acetylcholinesterase -> acetic acid + choline on postsynaptic membrane and extra cellular space

17

Mechanism of neurotransmitter release
4

Action potential depolarises the nerve terminal
Ca 2+ enters presynaptic
Binds to regulatory proteins and causes exocytosis
Neurotransmitter binds, exciting/inhibiting post synaptic

18

Electrical synapses
3

Passes directly through gap junctions
Docking of two hemichannels
Each hemichannel = 6 connexin/innexin

19

Classical neurotransmitters
3

ACH
Biogenic amines: noradrenaline, dopamine, serotonin, histamine
Amino acids: glutamate, GABA, glycine

20

Peptide neurotransmitters
2

Substance P
Opioids (endorphins, enkephalins)

21

Unconventional neurotransmitters
3

NO
ATP
Cannabinoids

22

Mechanism of an action potential
5

Depolarising stimulus
Na+ entry, more depolarisation
NA+ close, K+ open
Cell hyperpolarisation due to K+ loss
Channels close, resting potential

23

The 3 types of membrane channels

Voltage gated
Chemically gated
Mechanically gated

24

Graded potentials
5

Amplitude is proportional to stimulus strength
Densities and cell bodies
Lose strength with distance, due to current leak
Two potentials can summate
If reach supra threshold -> action potential

25

Action potential

All or none
Strength/duration due to frequency of action potentials
Axon hillock, no reduction in strength with distance
No summation due to refractory period
Can affect degradation enzymes and reuptake to prolong

26

Protective structures of the CNS
3

Cranium bones interconnected by immovable fibrous joints
Vertebrae are separated by intervertebral disks
Nerves of PNS enter and leave in spaces between vertebrae

27

The meninges
5

Dura mater
Arachnoid membrane
Subarachnoid space (contains CSF)
Pia mater (on brain surface)
Physical and chemical protection

28

Fluid compartments of the CNS
5

Volume of cranium 1L cells + 0.4L fluid
150 blood, 300 CSF
1st 2nd 3rd 4th CSF filled ventricles
CSF produced by choroid plexus- blood filtrate with cells removed, changed ionic composition and little protein

29

Nicotinic ACH receptor
3

Ionotropic receptor- fast time scale
Nicotine is an agonist
Open ions channels

30

Muscarinic ACH receptor
4

Metabotrophic receptor / g coupled
Muscadine is an agonist
M1, M3, M5 - activate phospholipase C -> DAG + IP3 messengers
M2, M4 - inhibit adenylate cyclase, reduces cAMP

31

Adrenergic receptor subtypes (noradrenaline receptor)
3

a1 - phospholipase C -> DAG and IP3
a2 - inhibits adenylate cyclase -> less cAMP
B1-B3 - activates adenylate cyclase

32

Inactivation of neurotransmitter
Affected by therapeutic drugs

Enzymatic degradation in the synaptic cleft
Reuptake into nerve terminal or glia -> enzymes
No uptake for ACH

Activity of enzymes
Affect reuptake
Mimicking /blocking action on receptor

33

Blood brain barrier
3

Absent in hypothalamus to allows hormone flow
Capillary endothelial cells have right junctions so use membrane transporters
Astrocytes surround capillaries and induce tight junction formation

34

Telencephalon

Cerebrum divided into left and right connected by corpus callosum
4- frontal (motor), parietal (sensory), temporal (audio), occipital (vision)
Basal ganglia- movement

Limbic system (memory and learning)
Hippocampus
Amygdala
Cingulate gyrus

35

Diencephalon

Thalamus- relays sensory
Hypothalamus- homeostasis and hormones of pituitary
Pineal gland- secrete melatonin, circadian rhythms

36

Mesencephalon

Superior and inferior colliculi- eye movement, auditory and visual
Substantial nigra and red nuclei- skeletal movement

37

Mentencephalon

Cerebellum- posture and balance
Pons- relay for cerebral cortex and cerebellum, breathing

38

Myelencephalon

Medulla oblongata- cerebral cortex -> spinal cord, breathing, swallowing

39

The spinal cord

Sensory nerves have cell bodies in dorsal root
Motor neurons have cell bodies in ventral horn -> ventral root

40

The efferent PNS

Somatic motor- efferent motor neurons project and control skeletal movement
Autonomic- inner ate smooth muscle and organs

41

The Afferent PNS

Carry information to the CNS from sensory receptors in organs

42

Somatic motor pathway

Have cell bodies in the ventral horn
Run from spinal cord to muscle
May innervate more than one muscle cell (several motor units)
ACH -> nACH receptors

43

Neuromuscular junction

Each Nicotinic ACH receptor binds 2ACH
Allows Na to enter the cell
Starts muscle contraction

44

Sympathetic pathway

Short preganglionic neuron
ACH -> nACH
Postganglionic releases noradrenaline to adrenaline receptor

45

Parasympathetic pathway

Long preganglionic neuron
ACH -> nACH
ACH released at Postganglionic -> muscarinic ACH receptor

46

Alzheimer's
Cause
Biochem
Treatment

Mutations in APP and presenillin, environment, other

a,b,y secretases cleave APP. Presenillin needed for y Secretase
AB42 fragments are toxic to neurons -> b-amyloid deposits
Neurofibrillary tangles of hyper phosphorylated tau -> helical filaments

Acetylcholinesterase inhibitors- prolong ACH
Possible Secretase inhibitors

47

Parkinson's
Causes
Pathology
Treatment

MPTP- oxidised to MPP+ which inhibits mitochondrial function
Genetics- SNCA gene -> alpha synuclein (never terminal protein). PARK2 -> Parkin (ubiquitin pathway, removes proteins).

Appearance of Lewy bodies (toxic alpha synuclein)
Degeneration of dopaminergic neurons of nigrostriatal pathway

L-DOPA to raise dopamine level (precursor)
Deep brain stimulation- electrodes

48

Pathology of MS
Causes of MS
Diagnosis
Treatment

Lesions -> scleroses in myelin sheaths of CNS
Loss of myelin

Infection- Epstein Barr virus, measles, herpes, pneumonia
Immune- molecular mimicry, antibodies against myelin
Genetics- 50 susceptibility genes, MHC genes

Hot bath
Nerve conduction
lumbar puncture
MRI

B-interferons

49

Relapsing remitting MS

Alternating illness and recovery, no deterioration

50

Secondary progressive MS

Deterioration, fewer remissions and incomplete recovery

51

Progressive relapsing MS

Alternating relapse and remission, progressive deterioration

52

Primary progressive MS

Progressive from the onset of the disease, no remission
10-15%

53

Guillian barre syndrome

Autoimmune
Antibodies attack myelin sheath
Complete recovery possible
Affects somatic motor, sensory neurons, autonomic neuron

54

Charcot Marie tooth disease

Inherited demyelinating disease
Weakness of foot and hand muscles
Reduced pain perception

Autosomal- PMP-22 (myelin maintainance) rarely Po (myelin compaction)

CMTX- connexin 32 gene causes faulty gap junctions, lack of nutrients to inner myelin layers

55

Myasthenia gravis

Antibodies attack nACH
Increases rate of receptor degradation
Postsynaptic defect

56

Lambert eaton myasthenia

Antibodies attack Ca channel in presynaptic
Reduces ACH release
Maybe cancer associated
Presynaptic defect

57

Congenital myasthenic syndromes

Autosomal recessive
Mutations in nACH receptor
CMSEA- episodic apnea. Mutation in choline acetylttransferase lack of ACH.

End plate ACHase deficiency- ACH not degraded

58

Depression
Treatment

Imbalances in central monoaminergic and cholinergic pathways in the limbic system
Lower activity with noradrenaline, dopamine and serotonin
Overactivity of ACH
Genes encoding synaptic proteins

MAOs- prevent breakdown of monoamines
SSRIs- block reuptake of serotonin

59

The 5 special senses

Vision
Hearing
Equilibrium
Taste
Smell

60

The 4 somatic senses

Touch/ pressure
Pain
Temperature
Proprioreception

61

Sensory transduction

Sensory -> electrical signals
Membrane potential change = generator potential (receptor and sensory) receptor potential (receptor distinct from sensory)

62

The sensory pathways

Enter spinal cord or brain stem (primary)
Ascending -> sensory cortex (2nd, 3rd)
All except olfactory pass through thalamus before cerebral cortex
All processed in different regions of sensory cortex

63

What the CNS needs to know about the sensory stimulus
5

Modality- nature I.e. Sound or light
Intensity and duration- pattern of action potentials
Location- timing of activation, topographic map, mechanoreceptors
Sensation- recognition of event
Perception- interpretation of event

64

Nociception

Mechanical, thermal, chemical stimulus
Fast pain- small myelinated, 12-30m/sec a-delta fibres (sharp)
Slow pain- unmyelinated C fibres, 0.5-2m/sec (dull)

Periphery -> spinal cord and thalamus -> somatosensory complex

65

Gating theory of pain

No pain- inhibitory interneuron stops C fibre contacting sensory neuron
Strong pain- inhibition blocked, C fibre activated and transmits
Modulation- stimulators and inhibitory signals together
Non painful by a-beta fibres (rubbing pain)
Therefore decreased painfulness

66

Gustation
Stimulus
Receptor
Neural pathway

Stimulus- sweet, bitter
Receptor- taste buds on toungue, epiglottis, soft palate
Pathway- primary -> medulla (processing) -> thalamus -> gustatory cortex (parietal lobe)

67

Taste bud sensory receptors

50-150 taste receptor cells, with support cells
Tastants are dissolved in saliva and mucus of mouth
Dissolved ligand bind to microvilli

68

Taste transduction 5

Ligand activate g coupled receptors
Intracellular signalling pathways activated
Ca2+ increases due to release and depolarisation, channels opened
Neurotransmitter released -> primary sensory neuron
Action potential

69

Olfaction

Odour stimulus
G coupled protein receptors on primary sensory neurons
Primary sensory -> olfactory bulb -> olfactory cortex

70

Pupillary light reflex

Constricted pupil reduced light
Dilated pupil increased light

71

Accomodation reflex

Flat lens - distant, ciliary relaxed, zonulas contract
Round lens - near, ciliary contract

72

Lens shape and refraction of light

Perpendicular- no refraction
Convex- focussed to a point
Concave- scattered
Parallel in distant, oblique in close
Decline with age

73

Long and short sightedness

Myopia (near)- focus point before retina
Hyperopia (far)- focus point after retina

74

Cataracts

Breakdown of the lens fibre structure, reduced vision/blindness
Mutations in crystallin prevent folding -> aggregation
Connexin mutations disrupt gap junctions disrupts ionic composition

Diabetes- galactose diffusion from plasma to the lens increases osmolarity and swelling and disruption of the lens structure

75

Visual pigments
Rod and cone cells

11-cis-retinal
Rods- rhodopsin (retinal + opsin)
Cones- blue, red and green opsin (colour blindness)

76

Photo transduction in rods

Inactive rhodopsin in dark, high cGMP, K+ open
Light activates rhodopsin -> opsin and retinal
Opsin decrease cGMP, closes CNG channels
Cell hyper polarised
Less neurotransmitter released
Recovery phase

77

Retinitis pigmentosa

1/3500
Pigment from degenerating rods is scavenged by retinal pigment epithelium -> excessive pigmentation
Loss of peripheral vision due to rode degeneration
Cones in fovea unaffected

Mutations in RHO gene (rod opsin)
Genes for photoreceptor development and maintainance

78

Macular degeneration

Age related -50+
Under 50= macular dystrophy
Dry form- macula and fovea destroyed
Wet from- growth of new blood vessels form choroid -> retina
Central vision reduced but no blindness
20+ genes

79

Structure of the cochlea

Scala vestibuli and scala tympani contain perilymph, similar to extra cellular fluid
Scala media (outer membrane of scala) contains endolymph, similar to intracellular fluid

80

Organ of corti

Between scalar tympani and vestibuli
Basilar membrane with hair cells above
Topped with tectorial membrane

81

Sound transduction mechanism

Sound waves funnelled to tympanic membrane
Vibrations transferred to malleus -> incus -> stapes
Stapes -> oval window -> cochlea
Fluid displacement in cochlea causes basilar membrane and hair cells to vibrate
Hair cells bend backwards or forwards against the tectorial membrane

82

Hair cells

Tips of stereocillia contain mechanical K channels
Stimulators- K open, depolarisation -> action potential in sensory
Destimulatory- hyperpolarisation, no action potential

83

Auditory pathway

Primary hair cells -> cochlear nuclei in medulla
Medulla -> pons -> midbrain -> thalamus
Pons split into ipsilateral and contralateral so that each side of the brain receives info from both ears
Thalamus-> temporal lob of cerebral cortex
Loudness and duration by action potentials
Pitch- vibration of basilar membrane, sloped thickness

84

Hearing loss
3 types

Conductive- external and middle ear impaired. Wax, infection, bones
Sensorineural- inner ear (hair cell degeneration) loud noise, genes.
Connexin 26 mutation- cannot recycle K+
Central- neural pathways damaged. Uncommon.

85

Cells of the PNS
2

Schwann cells- produce myelin, secrete neurotrophic factors
Satellite cells- form capsules around cell bodies in ganglia (clusters of cell bodies outside CNS)

86

Cells of the CNS

Oligodendrochtes- myelinates multiple axons at a time
Microglia- macrophage type cells
Astrocytes- secrete neurotrophic factors, take up neurotransmitters water and ions, provide substrates for ATP production, blood brain barrier
Ependymal cells- layer of epithelial that lines ventricles. Produce CSF. Some act as stem cells.