Exam #2 Flashcards

1
Q

the peripheral nervous system is comprised of both the ______ division and the ____ division

A

afferent, efferent

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2
Q

the afferent division of the peripheral nervous system contains ___ stimuli and ____ stimuli

A

sensory, visceral

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3
Q

the efferent division of the peripheral nervous system is comprised of the _____ nervous system and the ____ nervous system

A

somatic, autonomic

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4
Q

the somatic nervous system controls _____ neurons, which controls ______

A

motor, skeletal

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5
Q

the autonomic nervous system has 2 branches, what are they?

A

sympathetic and parasympathetic

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6
Q

both the sympathetic and the parasympathetic nervous systems control _____ muscle, _____ muscle, and ____

A

smooth, cardiac, glands

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7
Q

the autonomic nervous system innervates organs whose functions are not usually what?

A

under voluntary control

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8
Q

why are reflexes important for autonomic control

A
  • may involve sensory info causing changes in autonomic output, in order to return to a setpoint (negative feedback)
  • may elicit feedforward responses
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9
Q

sensory information from the autonomic nervous system may be processed within which 3 structures

A
  • hypothalamus
  • limbic system
  • spinal cord
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10
Q

what are the 2 effectors of the autonomic nervous system

A

visceral organs and blood vessels (also glands)

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11
Q

the actions of the autonomic nervous system require conscious control

True or False?

A

false, its actions are usually involuntary (without conscious intent or awareness)
-although, using biofeedback techniques it may be possible to learn to exert control over the ANS

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12
Q

are there some cases where the autonomic nervous system are activated by conscious control?

A

yes

  • ex: micturation (peeing)
  • the ability to not pee is an activation of the sympathetic branch
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13
Q

most visceral effectors need the ANS to function

True or False?

A

false, most visceral effectors do not need the ANS to function, only adjust their activity to match to body’s needs to maintain homeostasis (heart rate for example)

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14
Q

general autonomic nerve pathwat

A

-extends from CNS to an innervated organ

  • 2-neuron chain
  • preganglionic fiber (synapses with the cell body of second neuron)
  • postganglionic fiber (innervated the effector organ or tissue)
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15
Q

in a general autonomic nerve pathway, the preganglionic fiber has a cell body ______ the CNS, whereas the postganglionic fiber has a cell body ____ the CNS

A

within, outside

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16
Q

what is a ganglion

A

a mass or a group of neuronal cell bodies that form a knot-like mass of tissue

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17
Q

in the sympathetic branch of the autonomic nervous system, cell bodies of the preganglionic fibers originate from where?

A

originate in thoracic and lumbar regions of the spinal cord

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18
Q

in the sympathetic branch of the autonomic nervous system, the preganglionic fibers are ______ relative to the postganglionic fibers which are ____

A

short, long

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19
Q

what are the 3 possible things that axons from the sympathetic branch of the autonomic nervous system do after they exit the spinal cord?

A

1) make a synapse in a sympathetic chain ganglion
2) pass through sympathetic chain ganglia (SCG) and synapse in the adrenal medulla
3) pass through the SCG and synapse in a collateral ganglion

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20
Q

in the sympathetic division of the autonomic nervous system, preganglionic fibers release _____ whereas most postganglionic fibers release _____

A

acetylcholine (ACh), norepinephrine (NE)

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21
Q

it is said that the adrenal medulla is a modified sympathetic ganglion. Why is this?

A

in early development, groups of neurons leave the spinal cord to form postganglionic cells, small group of these instead of becoming postganglionic cells, migrate into and within the adrenal tissue

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22
Q

sympathetic neurons secrete ___% epinephrine and ___% norepinephrine

A

85, 15

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23
Q

in the parasympathetic division of the autonomic nervous system, fibers originate from the _____

A

cranial and sacral areas of the CNS

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24
Q

in the parasympathetic division of the autonomic nervous system, preganglionic fibers are relatively _____ compared to the postganglionic fibers which are ____

A

long, very short

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25
Q

in the parasympathetic division of the autonomic nervous system, the preganglionic fibers release ____ whereas the postganglionic fibers release ____

A

both acetylcholine (ACh)

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26
Q

both in the sympathetic and parasympathetic nervous systems does each postganglionic neuron receive synapses from many preganglionic cells (convergence)

True or False?

A

true

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27
Q

both in sympathetic and parasympathetic divisions of the autonomic nervous system does each preganglionic neuron branch many times to synapse on many different postganglioning neurons at a rate of 1:10 -
1:30 (divergence)

true or false?

A

false, this only happens in the SNS, the rate of the PNS is 1:4 (lower than SNS)

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28
Q

the sympathetic nervous system tends to respond as a unit

True or False?

A

true

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29
Q

the parasympathetic nervous system tends to respond as a unit

true or false?

A

false, in the parasympathetic nervous system, things like heart rate can be regulated independently of gut or liver, there’s enough individual control

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30
Q

4 of the cranial nerves have parasympathetic function, which are they?

A
  • oculomotor nerve: control the lens and the pupil of the eye
  • fascial nerve: tear glands, salivary glands, nasal glands
  • glossopharyngeal nerve: salivary glands
  • vagus nerve: 70-90% of all parasympathetic fibres, innervates the viscera
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31
Q

what are some characteristics of the vagus nerve?

A
  • it’s the 10th cranial nerve
  • vagus = “wandering”, called this because it innervates basically all viscera
  • has many branches
  • innervates all organs except the adrenal medulla and some parts of the colon
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32
Q

the ____ nerve carries sensory information from most of the viscera

A

vagus

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33
Q

what is the reflex arc of the vagus nerve?

A

1) the vagus nerve carries sensory info from most of the viscera. many of these sensory afferents project topographically to the nucleus of the solitary tract (abbreviated to NST or NTS), to the brainstem
2) the sensory info is processed within the NTS.
- the NTS may also project axons to higher parts of the brain, hypothalamus and cortex
3) vagus nerve carries efferent information to regulate organ function

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34
Q

the receptors between the pre and the post ganglionic cells are usually ______ receptors, whereas the receptors between the postganglionic cell and the target cell are usually _____ receptors

A

nicotinic, muscarinic

*in the parasympathetic division, sometimes the receptors between the postganglionic cell and target cell are nicotinic

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35
Q

which tends to have longer lasting effects: the sympathetic branch of the autonomic nervous system or the parasympathetic branch

A

sympathetic branch

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36
Q

why does the sympathetic nervous system tend to have a longer lasting effect than the parasympathetic nervous system?

A

1) achetylcholin is quickly broken down by acetycholinesterase
2) norepinephrine is more persistent than ACh. breakdown mechanisms are slower
- NE is transported back into the neuron
- NE is degraded by COMT or MAO
- NE picked up by the blood (where there are no degradative enzymes)

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37
Q

which receptors can we find on the target organs of the sympathetic nervous system (NE)?
(hint: “p-dibi”)

A
  • a1 receptors (phospholipase c)
  • a2 (decreae cAMP)
  • B1 (increase cAMP)
  • B2 (both increase and decrease cAMP)
  • B3 (increase cAMP)
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38
Q

which receptors can we find on target organs in the parasympathetic nervous system (ACh)?

A

-nicotinic AChR (ligand gated ion channel)

  • muscarinic AChR (GPCR):
  • M1 (phospholipase c)
  • M2 (decrease cAMP)
  • M3 (phospholipase c)
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39
Q

the sympathetic nervous system activates the ______ to release massive amounts of _____. This second messenger signalling often affects what?

A

adrenal medulla, epinephrine, ion channels

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40
Q

what are the effects of the sympathetic nervous system stimulation on the heart?

A

increased rate, increased force of contraction (of whole heart)

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41
Q

what are the effects of the parasympathetic nervous system stimulation on the heart?

A

decreased rate, decreased force of contraction (of atria only)

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42
Q

what are the effects of the sympathetic nervous system stimulation on the eye?

A

dilation of pupil

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43
Q

what are the effects of the parasympathetic nervous system stimulation on the eye?

A

constriction of pupil

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44
Q

what are the effects of the sympathetic nervous system stimulation on the exocrine pancreas?

A

inhibition of pancreatic exocrine secretion

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45
Q

what are the effects of the parasympathetic nervous system stimulation on the exocrine pancreas?

A

stimulation of pancreatic exocrine secretion (important for digestion)

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46
Q

what are the effects of the sympathetic nervous system stimulation on the salivary glands?

A

stimulation of small volume of thick saliva rich in mucus

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47
Q

what are the effects of the parasympathetic nervous system activation on the salivary glands?

A

stimulation of large volume of watery saliva rich in enzymes

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48
Q

the exocrine pancreas produces which enzymes?

A

trypsin, pancreatic lipase, and pancreatic amylase

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49
Q

what is dual innervation?

A

most of your internal organs have dual innervation (input from SNS and PNS)
-this is not always balanced (ex: digestive has much more PNS than SNS)

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50
Q

the effects of dual innervation are usually antagonistic

True or False?

A

false, the effects can be antagonistic or complimentary

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51
Q

what are some examples of the antagonistic functions of dual innervation?

A

the heart is innervated by both SNS and PNS

  • SNS increases heart rate and force of contraction
  • PNS decreases

The iris innervated by both

  • SNS innervated the pupillary dilator
  • PNS innervates the pupillary constrictor
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52
Q

give examples of the complimentary functions of dual innervation

A

activation of SNS and PNS produce similar results

Salivary glands are innervated by both
-both increase saliva production, but different kinds of saliva (SNS stimulated mucus production; PNS stimulates water, enzyme rich saliva)

Male sexual response, PNS responsible for erection, SNS responsible for ejaculation (point and shoot, memory trick)

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53
Q

not all target organs are subject to dual innervation. Which target organs are only innervated by the sympathetic branch?

A

adrenal medulla, sweat glands, smooth muscle of most blood vessels

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54
Q

what are the central nervous system centres that contribute to autonomic regulation?

A
  • limbic system (integration of sensory and emotional response with autonomic output)
  • hypothalamus (major control centre for autonomic output; hunger, thirst, thermoregulation, emotions, and sexuality)
  • brain stem (gives ride to nuclei of cranial nerves that mediate several autonomic responses)
  • spinal cord (autonomic responses as the defecation and micturation reflexes are integrated in the spinal cord)
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55
Q

look at figs. 12.3, 12.4, 12.5, 12.8, 12.9, 12.10

A

page #?

-somewhere between 371-394 or 378-398

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56
Q

what are the 3 types of muscle?

A
  • skeletal muscle (make up muscular system; also diaphragm)
  • cardiac muscle (found only in the heart)
  • smooth muscle (classified in two different ways (striated or unstriated; voluntary or involuntary)
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57
Q

which of the 3 types of muscle is multinucleated?

A

skeletal muscle

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58
Q

which of the 3 muscle types is not striated?

A

smooth muscle

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59
Q

which of the 3 types of muscle is stacked end to end?

A

cardiac muscle

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60
Q

which of the 3 types of muscle is compared to an intercalated disc?

A

cardiac muscle

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61
Q

controlled muscle contraction allows for 3 things, what are these things?

A
  • skeletal muscle allows for the movements of joints, limbs and whole body
  • smooth muscle and cardiac muscle control propulsion of contents through various hollow organs
  • emptying of contents of certain organs to external environment
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62
Q

skeletal muscle is controlled by which division of the nervous system? (central or peripheral)

A

CNS

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63
Q

the neurons in skeletal muscle have a cell body in the motor cortex synapse on motor neurons in the _____

A

spinal cord

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64
Q

skeletal muscle: motor neurons with cell bodies in the spinal cord send axons to synapse onto _____

A

muscle cells (nerve muscle synapse is called a neuromuscular junction (NMJ)

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65
Q

the group of muscle cells controlled by a motor neuron is a _____

A

motor unit

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66
Q

___% of axons cross through the medullary pyramids

A

95

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67
Q

in mammals, each muscle cell receives how many synapses?

A

only one

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68
Q

muscles that require fine control have very ______ convergence
ex: muscles of the eye

A

little

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69
Q

muscles that don’t require fine control can have very _____ convergence
ex: rectus femoris

A

high

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70
Q

in mammals, inhibitory synapses on muscle cells are quite frequent

true or false?

A

false, in mammals, inhibitory synapses on muscle cells do not exist

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71
Q

what is the size comparison of an neuromuscular junction synapse (NMJ) compared to a central synapse?

A

NMJ = 1000 um (squared)

central synapse = 0.05 um (squared)

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72
Q

why is the NMJ such a huge synapse?

A

because the postsynaptic membrane is folded and has a high density of nAChR (niconitic achetylcholine receptors) (hundreds of thousands)
-a.k.a. high density of ligand gated ion channels directly underneath presynaptic terminals

-this causes a massive release of ACh, causes a huge EPSP in the muscle fiber, depolarization will ALWAYS be enough to trigger an action potential (no summation)

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73
Q

what is the structure of a skeletal muscle?

A

muscle consists of a number of muscle fibers lying parallel by connective tissue

one single skeletal muscle is known as a muscle fiber

  • multinucleated
  • large, elongated, and cylindrically shaped
  • fibers usually extend entire length of muscle
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74
Q

what is the fluid inside the T-tubules of a skeletal muscle cell?

A

ECF

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75
Q

the T-tubules are a continuation of what?

A

the cell membrane has holes that lead to the T-tubules

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76
Q

the sarcoplasmic reticulum is full of what?

A

Ca++

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77
Q

what determines the length of one sarcomere

A

from z disc to z disc

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78
Q

what is the name of the line in the center of the sarcomere

A

m-line

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79
Q

what is the a-band in a sarcomere

A

sits between the z discs

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80
Q

what is a z disk in a sarcomere

A

sits between a-bands

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81
Q

the thick filaments are in the _____ of a sarcomere and the thin filaments are _____

A

middle, towards the edges

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82
Q

what are the 3 components of the myofibril

A

actin, myosin, and titin

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83
Q

what is the major component of a thick filament?

A

myosin

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84
Q

myosin

A

protein molecule consisting of two identical subunits shaped like a golf club

  • tail ends are intertwined around each other
  • globular heads project out at one end
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85
Q

what is the orientation of the heads and tails of a myosin molecule?

A

tails are oriented towards the center of the filament and globular heads protrude outward at regular intervals

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86
Q

which part of the myosin filament forms cross bridges between thick and thin filaments?

A

myosin heads

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87
Q

myosin has two important sites that are critical to contractile process, what are they?

A
  • an actin binding site

- a myosin ATPase

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88
Q

what is a cross bridge in muscle fiber contractile unit

A

cross bridge refers to the interaction between myosin and actin molecules (the interaction itself is called a cross bridge)

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89
Q

the thick filaments of a muscle contractile unit are made of _____, whereas the thin filaments are made of ____

A

myosin; actin, tropomyosin, troponin, nebulin, titin

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90
Q

primary structural component of thin filaments

A

actin

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91
Q

what are the spherical monomers that assemble into long chains in the actin chain

A

g-actin monomers

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92
Q

each actin molecule has a special binding site for attachment with the _____

A

myosin head

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93
Q

the binding of a myosin head to an actin monomer results in what?

A

contraction of the muscle fiber

-this interaction is key to produce movement

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94
Q

topomyosin

A
  • regulatory protein
  • thread-like molecules alongside the groove of the actin spiral
  • tropomyosin covers the myosin binding sites
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95
Q

which regulatory protein covers the myosin binding sites on the actin molecules?

A

tropomyosin

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96
Q

troponin is made of 3 polypeptide units, what do they bind to?

A
  • one binds to tropomyosin
  • one binds to actin
  • one binds with Ca++
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97
Q

what effects do Ca++ levels have on the effects of troponin on tropomyosin?

A
  • when there’s a low level of Ca++, troponin stabilizes the action of tropomyosin
  • when there’s lots of Ca++, troponin pulls tropomyosin out of the way so that the myosin binding site is open
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98
Q

describe the action of troponin on muscle contraction

A
  • when not bound to Ca++, troponin stabilizes tropomyosin in blocking position over actin’s cross-bridge binding sites
  • when Ca++ binds to toponin, tropomyosin moves away from blocking position
  • with tropomyosin out of the way, actin and myosin bind, interact at cross-bridges
  • muscle contraction occurs
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99
Q

titin

A
  • structural protein
  • giant elastic protein (one of the biggest in mammalian genome)
  • joins m-lines to z-lines at opposite ends of the sarcomere
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100
Q

what are the 2 important roles of titin?

A
  • help stabilize position of thick filaments in relation to thin filaments
  • improves muscle’s elasticity
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101
Q

nebulin

A

aligns actin filaments

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102
Q

the muscle ______ when actin and myosin slide past each other

A

shortens

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103
Q

when a muscle contracts, the A-band gets smaller along with the length of the filaments

true or false?

A

false,
the size of the A-band never changes length and neither does the length of the thin filaments
-what changes is the amount of overlap between the two

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104
Q

what structures shorten when a muscle contracts?

A

the H-zone and the I-band both shorten

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105
Q

what is the role of Ca++ in a muscle cell to be able to generate tension?

A

1) Ca++ levels increase in the cytosol
2) Ca++ binds to troponin (TN)
3) TN-Ca++ complex pulls tropomyosin away from actin’s myosin-binding site
4) myosin binds strongly to actin and completes power stroke
5) actin filament moves

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106
Q

what initiates the contraction of a muscle cell?

A

Ca++

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107
Q

in its relaxed state, the myosin head is ______, and ______ partially blocks the binding site on actin, myosin is weakly bound to actin

A

cocked, tropomyosin

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108
Q

power stroke

A

cross bridge bends, pulling thin myofilament inward

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109
Q

the phase of muscle cell contraction where the cross bridge detaches at the end of the power stroke and returns to its original conformation

A

detachment

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110
Q

but these in order from first to last (phases of muscle cell contraction)

a) detachment: cross bridge detaches at the end of power stroke and returns to original position
b) binding: cross bridge binds to more distal actin molecule
c) binding: myosin cross bridge binds to actin molecule
d) power stroke: cross bridge bends, pulling thin myofilament inward

A

c, d, a, b

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111
Q

actin and myosin contract along with the contraction of a muscle cell

true or false?

A

false, actin and myosin do not contract

-myosin is properly called a motor protein: a protein that hydrolyzes ATP to convert chemical energy to carry out mechanical work

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112
Q

what is a motor protein?

A

a protein that hydrolyzes ATP to convert chemical energy to carry out mechanical work

ex: myosin

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113
Q

look at fig 12.9 and remember cycle

A

p.?

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114
Q

explain the 4 steps of the contraction cycle of a muscle cell

A

1) ATP binds to myosin. myosin releases actin
2) myosin hydrolyzes ATP. energy from ATP rotates the myosin head to the cocked position. myosin binds weakly to actin
3) power stroke begins when tropomyosin moves off the binding site (there is a rapid increase of intracellular Ca++ at this point)
4) myosin releases ADP at the end of the power stroke

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115
Q

the sarcoplasmic reticulum is closely related to the T-tubules and has a high [ ] of Ca++

true or false?

A

true

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116
Q

how does the sarcoplasmic reticulum have such a high [ ] of Ca++?

A

SR has powerful Ca++ATPase transporter
-uses ATP to pump Ca++ from cytoplasm into SR

SR also has Ca++ binding protein called calquestrin
-help maintain high [Ca++]

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117
Q

T-tubules run ______ from the surface of the muscle cell membrane into central portions of the muscle fiber

A

perpendicular

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118
Q

T-tubules are aligned on the edges of the ____-band

A

A

thick filaments, myosin

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119
Q

an action potential on the surface of a membrane also invade T-tubules

true or false?

A

true

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120
Q

what is the effect of the spread of an action potential down a T-tubule on the sarcoplasmic reticulum?

A
  • the spread of action potential down a T-tubule triggers the release of Ca++ from the sarcoplamic reticulum into the cytosol
  • this rapid increase is what’s responsible for binding of actin and myosin
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121
Q

an action potential in a t-tubule opens the voltage-gated Ca++ channels (dihydropyridine receptor) _____ and opens the ryanodine receptors on the sarcoplasmic reticulum _____. This is because the ____ of the ryanodine receptor is physically attached to the voltage gated Ca++ channel of the t-tubule

A

directly, indirectly, foot

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122
Q

the opening of the ryanodine receptor on the sarcoplasmic reticulum allows a massive flood of Ca++ into the cytoplasm via _____

A

because of the [ ] gradient

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123
Q

what are the two purposes of the voltage gated Ca++ channel (dihydropyridine receptor) in the T-tubules?

A

1) to act as a voltage sensor that can open the ryanodine receptor
2) lets in small amount of Ca++, contributes to the opening of RyR (ryanodine receptor)

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124
Q

thinking about what we’ve learned in the whole semester, explain the process of initiation of muscle action potential and excitation contraction coupling

A

1) an AP invades the presynaptic terminal and causes release of ACh
2) ACh binds to the receptor, allows entry of Na+, causes EPSP large enough to trigger AP
3) the AP invades the T-tubule system
4) the AP causes the DHP (receptors of t-tubules) to open, and in turn, open the RyR channel. this causes a massive release of Ca++, and increase in intercellular Ca++ [ ]
5) Ca++ binds troponin. troponin pulls tropomyosin away from myosin binding site on actin protein
6) power stroke
7) actin filaments slide towards centre of the sarcomere
8) free Ca++ pumped back into SR

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125
Q

rigor mortis

A
  • 3-4 hours after death, peak at 12 hours
  • after deatch, intracellular Ca++ rises (leaks out of SR)
  • Ca++ allows troponin-tropomyosin complex to move aside and allow myosin cross bridges to bind actin
  • but ATP is required to separate myosin from actin, dead cells can’t produce ATP, so once bound, the cross bridge can’t detach
  • rigor mortis subsides when enzymes start to break down myosin heads
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126
Q

explain the process that leads to the relaxation of a muscle

A
  • AP stop ariving at NMJ
  • ACh dissociates from AChR, gets degraded
  • Ca++ ATPase pumps free Ca++ back into SR
  • Ca++ dissociates from troponin, pumped bacj into SR
  • tropomyosin moves back into position, blocking cross bridge binding sites
  • muscle ceases to maintain tension
  • actin and myosin slip past each other (pulled by titin, pulled by antagonistic muscle)
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127
Q

what is myasthenia gravis

A
  • autoimmune disorder
  • antibodies block ACh binding sites on skeletal muscle
  • binding causes damage to tissue of muscle cell
  • not enough ACh is bound to create action potentials anymore
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128
Q

what are common symptoms of myasthenia gravis?

A
  • a drooping eyelid
  • blurred or double vision
  • slurred speech
  • difficulty chewing and swallowing
  • weakness in the arms and legs
  • chronic muscle fatigue
  • difficulty breathing

i.e. muscle weakness

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129
Q

what are some treatments for myasthenia gravis?

A
  • anticholenesterase treatment (drugs that inhibit ACh-esterase within the NMJ)
  • these allow ACh to remain in the NMJ longer
  • ex: pyridostigmine (degraded over 3-6 hours)
  • neostigmine (degrades over 1 hour)

other treatments:

  • immunosuppression
  • surgery (Ex: 10-15% of people with this have tumors, if the tumour is removed, can help symptoms)
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130
Q

what are the contraction-relaxation steps that require ATP

A
  • splitting of ATP by myosin ATPase for power stroke
  • active transport of Ca++ back into SR
  • fuel Na+/K+ ATPase

-so, constant source of energy is needed

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131
Q

what are the 3 energy sources for muscle contraction?

A

1) creatine phosphate: first energy storehouse tapped at onset of contractile activity
2) oxidative phosphorylation: takes place within muscle mitochondria if sufficient O2 is present
3) glycolysis: support anaerobic or high-intensity exercise (last resort)

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132
Q

creatine phosphate

A
  • during times of rest when ATP demand is low, muscle stores energy in the form of creatine phosphate
  • first store of energy tapped to fuel muscle contraction
  • provides 4-5 times the energy of stored ATP
  • limited supply (only a few minutes)
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133
Q

how does creatine phosphate work?

A

at rest, there’s lots of ATP around, creatine takes ATP and phosphate to create creatine phosphate
-good storage place for this high energy bonds

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134
Q

oxidative phosphorylation

A

The process that provides energy during light to moderate exercise

  • uses stores of glycogen in muscle (30 min)
  • good yield of ATP
  • aerobic exercise
  • adequate supply of oxygen

To maintain adequate oxygen

  • increase ventilation
  • increase heart rate and force of contraction
  • dilate skeletal blood vessels
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135
Q

glycolysis

A
  • primary source of ATP when oxygen supply is limited (during intense exercise)
  • rapid supply of ATP (only a few enzymes involved)
  • very low ATP yield (only 2 per glucose molecule; lactic acid, acidifies muscle and contributes to fatigue)
  • duration of anaerobic glycolysis is limited
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136
Q

what causes muscle fatigue?

A

Central fatigue

  • CNS (above psychological aspects; could be decreased output of motor neurons from cortex)
  • psychological

Peripheral fatigue

  • decrease in ACh
  • receptor desensitization
  • changes in RMP (because of extracellular K+)
  • impaired Ca++ release
  • pH
  • others…

the lack of ATP is not thought to be a factor***

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137
Q

the action potential and the contraction of a skeletal muscle happen almost simultaneously

true or false?

A

false, there is a latency period from when the action potential is generated to the time the muscle contracts (approx. 2 ms to generate action potential in motor neuron and skeletal muscle, 10-100 ms to contract muscle)

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138
Q

the total amount of tension generate by s skeletal muscle is dependent on the _____ of the motor neuron

A

firing frequency

-can be single twitch or summation

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139
Q

what is the difference between unfused tetanus and complete tetanus in a skeletal muscle?

A

complete tetanus is not able to generate the peak amount of tension that the unfused tetanus can reach

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140
Q

in _____ tetanus, fatigue causes the muscle to lose tension despite continuing stimuli

A

complete

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141
Q

what are 2 different views on what leads a muscle to reach its peak amount of tension?

A
  • some people think intracellular Ca++ reaches its maximum (saturates) after first action potential (summation and tetanus develop because of sustained elevation of increased Ca++ allows greater exposure of actin bindings sites and therefore maximizes interaction with myosin (effect is time dependent)
  • other people think it takes several APs to increase intracellular Ca++ enough to saturate actin’s myosin binding sites
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142
Q

takes several AP to cause generation of maximal tension

true or false

A

true

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143
Q

if there is less overlap between the thick and thin filaments, what effects does this have on a muscle’s ability to generate tension?

A

this reduces the number of possible interaction sites, lessening tension

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144
Q

by providing more overlap between the thick and thin filaments, what effects does this have on a muscle’s ability to generate tension?

A
  • the muscle fiber is pushed together so much that the myosin is interacting with the z-discs, and actin molecules are overlapping
  • crowding molecules leads to insufficient interaction between binding sites and myosin heads = less tension
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145
Q

what are the 3 types of motor units found in most mammals

A
  • slow twitch oxidative (red muscle)
  • fast twitch oxidative-glycolytic (red muscle)
  • fast twitch glycolytic (white muscle)
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146
Q

in turkey, muscle fiber groups are ____, whereas in mammals, muscle fiber groups are _____

A

together, interspersed

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147
Q

slow twitch oxidative motor unit (slow fatigue resistant)

A
  • small amounts of tension (compared to other two muscle types), slowly
  • capable of generating tension for long periods of time without running down energy stores
  • large number of mitochondria
  • small fibres
  • well vascularized, myoglobin (to facilitate oxygen transfer from blood (presence of myoglobin is what makes the muscle dark
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148
Q

fast twitch oxidative-glycolytic (fast fatigue resistant)

A
  • generate a lot of tension, moderately fast
  • somewhat resistant to fatigue
  • moderate number of mitochondria
  • fibres are larger than slow twitch muscles
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149
Q

fast twitch glycolytic (fast fatiguable)

A
  • white muscle
  • generate the most tension
  • fatigue rapidly
  • few mitochondria (anaerobic catabolism)
  • fibres are larger than slow twitch
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150
Q

both fast twitch muscles are able to generate their maximum amount of tension within ___ ms, while slow twitch muscle are able to generate their max amount of tension within ___ ms

A

25, 50

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151
Q

one muscle may have many motor units of different fiber types

true or false?

A

true

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152
Q

what are the first motor units recruited?

A
  • slow twitch fatigue resistant (red oxidative) (weakest are recruited first)
  • each motor unit has only a few fibres
  • small motor neuron
  • takes much less synaptic input to put these motor neurons to threshold
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153
Q

what are the 2nd motor units recruited?

A
  • motor units that include fast fatigue resistant fibres

- these motor neurons are slightly larger

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154
Q

what are the 3rd and last motor units recruited?

A
  • fast fatiguable (=fast twitch glycolytic, white muscle)

- the largest motor unit, includes most fibres

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155
Q

what is the size principle in the recruitment of motor units?

A

slow twitch is activated first (smallest), then fast fatigue resistant, then fast fatigable (largest)

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156
Q

one motor neuron can innervate more than one type of muscle

true or false?

A

false

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157
Q

general characteristics of cardiac muscle cells

A
  • interconnected by intercalated discs and form functional syncytia
  • within intercalated discs there are two kinds of membrane junctions (desmosomes and gap junctions)
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158
Q

what are the 3 types of cardiac muscle cells

A

1) myocardial autorhythmic cells
2) myocardial contractile cells (working cells)
3) conducting cells

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159
Q

cardiac muscle: myocardial autorhythmic cells

A
  • initiate and maintain electrical activity in the heart (generate their own action potentials without electrical stimulus)
  • do not contract
  • have gap junctions
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160
Q

cardiac muscle: myocardial contractile cells (working cells)

A
  • 99% of cardiac muscle cells
  • contractile, MUSCLE part of the heart, do mechanical work of pumping (either in the ventricle or the atrium)
  • joined electrically by gap junctions
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161
Q

cardiac muscle: conducting cells

A
  • carry electrical signals from the pacemakers to the contractile cells
  • gap junctions
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162
Q

where does the cardiac impulse originate?

A

at the SA node (sinal atrial node)

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163
Q

explain the process of electrical conduction in the heart

A
  • cardiac impluse originates at SA node
  • action potential spreads throughout right and left atria
  • impulse passes from atria into ventricles through AV node (only point of electrical contact between the chambers)
  • action potential briefly delayed at AV node (ensures atrial contraction precedes ventricular contraction to allow complete ventricular filing)
  • impulse travels rapidly down interventricular septum by means of bundle of His
  • impulse rapidly disperses throughout the myocardium by means of Purkinje fibers
  • rest of ventricular cells activated by cell to cell spread of impulse through gap junctions
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164
Q

what kind of cells initiate action potentials in cardiac cells?

A

autorhythmic cells

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165
Q

what is the resting membrane potential of a cardiac muscle cell?

A

there is no real resting membrane potential, it is rather a spontaneous conduction of action potentials by the autorhythmic cells

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166
Q

what is the pacemaker potential

A

membrane slowly depolarizes “drifts” to threshold, initiate action potential, membrane repolarizes to -60 mV (cardiac cell)

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167
Q

autorhythmic cells: I(f)

A

a Na+ current

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168
Q

autorhythmic cells: ICa(T)

A

fast calcium current

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169
Q

autorhythmic cells: ICa(L)

A

slow Ca++ current

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170
Q

in a skeletal muscle cell, ____ flows inside the cell during an action potential, in a cardiac muscle cell, ____ is used instead

A

Na+, Ca++

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171
Q

explain the steps of an action potential in contractile cells of a cardiac muscle

A

0) Na+ channels open slowly
1) Na+ channels inactivate once AP reaches its peak
- rapid depolarization

2) Ca++ channels open; fast K+ channels close
3) Ca++ channels close; slow K+ channels open
- rapid partially early repolarization, prolonged period of slow repolarization (plateau phase)

4) cell goes back to resting membrane potential
- rapid final repolarization phase

**there is no hyperpolarization afterwards

** also, membrane potential is more negative (-80mV)

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172
Q

why is the repolarization phase of cardiac contraction cells so long?

A
  • plateau is primarily due to the activation of slow L-type Ca++ channels
  • this long action potential ensures adequate ejection of blood
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173
Q

how does the long action potential of contractile cells avoid tetanus?

A

long AP causes long refractory period and long contraction

-this refractory period overlaps the tension curve

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174
Q

refractory period of skeletal vs cardiac muscle cell

A

1) skeletal muscle fast twitch fiber: the refractory period is very short compared with the amount of time required for the development of tension
- skeletal muscles that are stimulated repeatedly will exhibit summation and tetanus (unlike cardiac muscle)

2) cardiac muscle fiber: the refractory period lasts almost as long as the entire muscle twitch
- long refractory period in a cardiac muscle prevents tetanus

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175
Q

excitation-contraction coupling in cardiac contractile cells

A

-Ca++ entry through Ca++ channels in T-tubules triggers massive release of Ca++ from SR to RyR (not connected to RyR receptors,
opening of these channels caused by entry of Ca++)
(compared to RyR in skeletal muscle)

  • Ca++ induced Ca++ release leads to cross-bridge cycling and contraction
  • key role for secondary active transport
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176
Q

smooth muscle

A
  • smooth muscle is highly variable
  • must operate over a range of lengths
  • layers may run in several directions (intestine for example, circular and longitudinal smooth muscle)
  • small, spindle shaped cells with one nucleus
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177
Q

what is the speed of contraction of smooth muscle relative to other muscle types?

A

contracts and relaxes much more slowly

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178
Q

what is the energy expenditure of a smooth muscle relative to other muscles?

A

uses less energy skeletal or cardiac muscle

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179
Q

_____ muscle sustains contraction for extended periods of time

A

smooth

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180
Q

_____ muscles are the slowest to contract and to relax

A

smooth (and then skeletal and then cardiac)

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181
Q

what are the 3 ways we can classify smooth muscle?

A
  • by location (vascular, gastrointestinal, urinary, respiratory, reproductive, ocular (this is the most specific classification))
  • by contraction pattern (phasic smooth muscles = contract then relax; tonic smooth muscles = active all the time, gets signals to relax, then contract when signal is gone)
  • by communication with neighbouring cells (single-unit smooth muscle, or visceral smooth muscle = all smooth muscle in that tissue behaves as one; multi unit smooth muscle = each individual smooth muscle cell is innervated and behaves independently from its neighbours)
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182
Q

phasic smooth muscles can either be ______ (ex: esophagus) or can work in cycles between _____ and ______ (ex: intestine)

A

relaxed, contraction, relaxation

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183
Q

tonic smooth muscles can either be contracted and release when needed (ex: sphincter) , or can ________ as needed (vascular smooth muscle)

A

vary as needed, but contraction is always happening

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184
Q

smooth muscle classification: communication with neighbouring cells

A

1) single unit smooth muscle cells are connected by gap junctions, and the cells contract a single unit (not all the muscle cells are directly innervated)
b) multi-unit smooth muscle cells are not electrically linked, and each cell must be stimulated independently (they could behave independently but they probably won’t)

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185
Q

smooth muscle is arranged in sarcomeres

true or false?

A

false

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186
Q

what kind of signal is needed to initiate contraction of a smooth muscle cell?

A

electrical, chemical, or both

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187
Q

smooth muscle cells are controlled by the ____ nervou system

A

autonomic

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188
Q

smooth muscle cells have very specialized receptor regions on their post-synaptic membranes

true or false?

A

false, smooth muscle cells lack specialized receptor regions, they have neurotransmitter receptors dispersed all over the cell membrane

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189
Q

in smooth muscle ____ is from the extracellular fluid and sarcoplasmic reticulum

A

Ca++

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190
Q

in smooth muscle, ____ initiates a cascade ending with phosphorylation of myosin light chain and activation of myosin ATPase

A

Ca++

this is different from the role Ca++ plays in generating tension in skeletal and cardiac muscle

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191
Q

in smooth muscle, _______ filaments and protein ______ form a cytoskeleton

A

intermediate, dense bodies

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192
Q

in smooth muscle, what attaches to the dense bodies of the muscle cell?

A

actin

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193
Q

in smooth muscle cells, each myosin molecule is surrounded by ______

A

actin filaments

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194
Q

how do T-tubules differ in smooth muscle?

A

-there are no T-tubules, but there are caveolae (small invaginations in the cell)

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195
Q

in smooth muscle, sarcoplasmic reticulum is more organized

true or false?

A

false, SR varies and is less organized

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196
Q

actin is more plentiful in which type of muscle?

A

muscle that is not striated (smooth muscle)

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197
Q

troponin is found in all types of muscle cells

true or false?

A

false, there is no troponin in smooth muscle

198
Q

is there more or less myosin found in smooth muscle?

A

less myosin

  • myosin filaments are longer
  • entire surface of filament is covered with myosin heads
199
Q

there is _____ cytoskeleton in smooth muscle

A

additional (intermediate filaments and dense bodies)

200
Q

myosin pulls actin molecules in opposite directions to generate tension in which type of muscle cell?

A

smooth muscle

201
Q

what is the biggest difference in the myosin of smooth muscle comapred to the myosin in other muscle?

A

myosin light chains: play a key role in regulating activity of myosin and its ability to bind with actin

202
Q

smooth muscle contraction

A

1) intracellular Ca++ [ ] increase when Ca++ enters cell and is released from SR
2) Ca++ binds to calmodulin (CaM)
3) Ca++-calmodulin activates myosin light chain kinase (MLCK)
4) MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity (that hydrolyzes ATP and contribute to power stroke)
5) active myosin crossbridges slide along actin and create muscle tension

203
Q

smooth muscle relaxation

A

1) free Ca++ in cytosol decreases when Ca++ is pumped out of the cell or back into the SR
2) Ca++ unbinds from calmodulin, MLCK activity decreases
3) myosin phosphatase removes phosphate from myosin light chains, which decreases myosin ATPase activity
4) less myosin ATPase activity results in decreases muscle tension

204
Q

if you ______ phosphatase, you improve the ability of that muscle cell to generate tension. If you ______ phosphatase activity, even if you have the same amount of Ca++, you can’t generate as much tension

A

decrease, increase

205
Q

changes in phosphatase activity alter ______ responses to Ca++

A

myosin’s

206
Q

smooth muscle contraction: store-operated Ca++ channels

A
  • decreased Ca++ stores in smooth muscle cells can activate these channels
  • these open to allow Ca++ to enter smooth muscle cell, increased Ca++ leads to muscle contraction
207
Q

smooth muscle contraction: membrane channels

A
  • activated by depolarization or stretch
  • causes an increase in intracellular Ca++
  • leads to muscle contraction
208
Q

smooth muscle contraction: membrane receptors

A
  • activated by signal ligands
  • either increases IP3 or activates modulatory pathwats

modulatory pathways:
-alter MLCK or myosin phosphate which leads to muscle contraction (or inhibition of muscle contraction)

Increased IP3:

  • there are IP3 receptors on the SR
  • activates channels on SR
  • Ca++ release which leads to muscle contraction
209
Q

what are the 3 different channels (smooth muscle) that can be activated in sarcoplasmic Ca++ release

A

1) ryanodine receptor (RyR) calcium release channel
- Ca++-induced calcium release (CICR)
2) IP3-receptor channel (DAG or IP3 binding)
3) store operated Ca++ channels (still don’t know exactly how these works, jus that they function physiologically)

210
Q

what are the 3 types of channels on smooth muscle that allow calcium entry into the cells

A

1) voltage gated Ca++ channels (activated by membrane depolarization)
2) ligand gated Ca++ channels, or receptor operated calcium channels (ROCC)
- this channel is selectively permeable to Ca++
3) stretch-activated calcium channel
- open when pressure or other force distorts cell membrane
- known as myogenic contraction (arteries)

211
Q

many ______ muscles are controlled by both sympathetic and parasympathetic neurons

A

smooth

212
Q

hormones and paracrines can cause ______ muscle contraction

A

smooth

213
Q

_____ constricts smooth muscle of airways (asthma)

A

histamine

214
Q

_____ relaxes smooth muscle of blood vessels (male sexual response, exploited by viagra, cialis)

A

nitric oxide

215
Q

smooth muscle contraction: electromechanical coupling

A
  • contraction caused by electrical signaling or mechanical signaling
  • contraction dependent on changes in membrane potential
216
Q

smooth muscle contraction: pharmacomechanical coupling

A
  • contraction caused by chemical signaling

- no changes in membrane potnetial required

217
Q

______ potentials fire actoin potnetials whent hey reach threshold (smooth muscle) (in the GI tract)

A

slow wave

218
Q

_____ potentials always depolarize to threshold (smooth muscle) (in the GI tract)

A

pacemaker

219
Q

_______ occurs when chemical signals change muscle tension through signal transduction pathways with little or no change in membrane potential

A

pharmacomechanical coupling

220
Q

comapare the internal muscle structure of all three types of muscles

A
  • skeletal: t-tubules and sarcoplasmic reticulum
  • smooth muscle: no t-tubules; sarcoplasmic reticulum
  • cardiac: t-tubules and sarcoplasmic reticulum
221
Q

compare the structures that control movement of each type os muscles

A
  • skeletal: Ca++ and troponin, fibers independent of one another
  • smooth: Ca++ and calmodulin; some fibers electrically linked via gap junctions, others independent
  • cardiac: Ca++ and troponin; fibers electrically linked via gap junctions
222
Q

compare the initiation of contraction of each muscle type

A
  • skeletal: requires ACh from motor neuron
  • smooth: stretch, chemical signals. can be autorhythmic
  • cardiac: autorhythmic
223
Q

poison

A

a substance that can cause illness or death when introduced into an organism

224
Q

toxin

A

a substance produced in an organism that can cause illness or death when introduced into an organism

225
Q

venom

A

toxin which is typically injected into an animal by another

226
Q

which deadly substance is found in puffer fish? what organ does it affect?

A
  • TTX

- gonads, liver (by affecting voltage gated Na+ channels)

227
Q

what was the role of TTX in the movie Serpent and the Rainbow?

A

-a witch doctor could create and maintain zombies using TTX and extract from Datura plant (contains hallucinogens like scopolamine and other alkaloids

228
Q

curare in 1596

A
  • “blowgun poison”
  • in 1596 Sir Walter Raleigh talked about poisoned arrows in his book (he was talking about curare)
  • paralytic poison used by natives of South America on arrows and blowgun darts
229
Q

what are the medical uses for TTX?

A
  • blocks voltage-gated Na++ channels, so it does make an effective anaesthetic
  • not membrane permeant, so it cannot be topically applied
  • stable chemical, high affinity, so takes a long time to wash out

-Na+ channel blockers like benzocaine, lidocaine, and cocaine are much more effective and safe anaesthetics

230
Q

what is curare? what does it do?

A
  • blowgun poison is amix of toxic molecules, d-tubocurare is a purified component = curare
  • mechanism of action was discovered in 1934
  • it binds to the AChR at the same position occupied by ACh (competitive antagonist)
  • prevents ACh from causing an EPSP and eliminates subsequent muscle contractions
  • death results from paralysis of diaphragm
231
Q

how do we use curare in modern medicine?

A
  • in 1942 a Canadian Harold Griffith was the first to systematically use curare during surgery
  • several other had experimented with using curare to lower amount of anaesthetic use during surgery (this causes flaccid muscle paralysis, makes wound closure much easier, without it, muscles tense up even if the person is under anaesthetic)
  • today, pancuronium (a safer synthetic analogue of d-tubocurare) us used instead of curare for surgery (and lethal injection)

-even if you give someone a proper dose, you still haven’t knocked them out, they can still feel everything that’s going on

232
Q

what is the active ingredient in pot? what is its role in plants?

A
  • tetrahydrocannabinol (THC)

- assumed to be a protective chemical in plants

233
Q

is THC hydrophilic or hydrophobic?

A

THC is very lipid soluble, so very hydrophobic or lipophilic

-this is what makes THC so available to your nervous system

234
Q

the endocannabanoid system

A
  • THC is an agonist for the endocannabanoid receptors CB1 and CB2
  • CB1 receptors located in cells throughout the CNS, but on presynaptic terminals (this is the most strongly expressed g-protein coupled receptor in the nervous system- it decreases the synthesis of cyclic AMP)
  • CB2 receptors located in cells of the immune system, skeletal muscle
  • the natural ligand is called an endocannabanoid
  • there may be more cannabanoid receptors
235
Q

explain the physiological process of the effects of THC on the nervous system

A
  • glutamate acts via NMDA receptors to increase intracellular Ca++
  • rise in Ca++ causes synthesis and release of endocannabanoids
  • endocannabanoids decrease cAMP, and decrease release of neurotransmitter (usually GABA)
  • THC saturates the system, causes alteration of neurotransmission in many areas of the cortex (there aren’t specific pathways that are being altered, every pathway that uses GABA will be altered)
236
Q

why is THC associated with the munchies?

A

-one of the specific effects of THC is to allow an increase in neuronal activity in hypothalamic areas that regulate appetite

237
Q

how was the exploration of cannabanoids related to weight loss remedies?

A
  • the french pharma company created a marketed Rimonibant: a drug to block the CB1 receptor
  • idea is to use it to inhibit appetite and cause weight loss
  • some people had the opposite effect while using the drug and drugs was not effective enough
238
Q

what is botox

A
  • botox is a purified bacterial toxin: from the bacterium Clostridium botulinum
  • called “sausage poison” because it was often found in improperly handled meat
  • one of the most toxic substances known to mankind (1 gram of the toxin can kill 1-10 million people)
  • in the late 1980’s, doctors used botulinum toxin to treat patients suffering from eye muscle disorders and headaches (by paralyzing muscles in the neck)
239
Q

how does botox work?

A
  • the toxin is taken into nerve terminals by endocytosis (very stable protein, does not get destroyed)
  • once inside the nerve terminal the toxin degrades the proteins that are responsible for releasing synaptic vesicles
  • the protein has a very long half life in the nerve terminals (weeks)
  • stops release of neurotransmitter from synaptic terminals (ACh)
  • causes long-lasting muscle paralysis
240
Q

cone snail toxin

A
  • cone snail toxin is a mixture of hundreds of toxins
  • physiologists and toxicologists have isolated various components (block numerous ion channels and membrane receptors; one specific component blocks specific type of voltage gated Ca++ channels)
241
Q

explain the physiological process of cone snail toxin on the nervous system

A

1) action potential travels down axon, depolarization opens voltage gated Ca++ channels, this allows Ca++ to enter presynaptic terminals
2) Ca++ entry causes some synaptic vesicles to fuse with presynaptic membrane and release their neurotransmitter contents into the synaptic cleft

**BUT, when cone snail toxin is present these Ca++ channels are blocked and Ca++ is no longer released; instant paralysis

242
Q

what are some medical uses for cone snail toxin?

A
  • in particualr, one component binds to a Ca++ channel variant within the spinal cord
  • team discovered that conotoxin is very effective at blocking chronic pain
  • name of drug is ziconotide (annual sales of 15-20 million)
243
Q

what is the main difference in TTX, botox, curare, and cone snail toxin?

A

-they all cause paralysis but by blocking different receptors

  • TTX = Na+ receptors
  • curare = ACh receptors
  • botox= degrading proteins
  • cone snail toxin = Ca++ receptors
244
Q

endocrinology as a science

A

homeostatic control mechanisms -physiological systems need communication and coordination
-ex: metabolism, salt and water balance, temperature, reproduction, growth

began in the early 20th century with two researchers William Bayliss and Ernest Starling
-interested in was the secretion of alkaline juive in the duodenum under nervous or chemical control

245
Q

what did Ernest Starling deduct in regard to endocrinology and its relationship with pharmacology?

A
  • endocrinology is the basis of pharmacology

- cannot design drugs without understanding how natural substances work

246
Q

more than one hormone can be produced in one endocrine gland

true or false

A

true

247
Q

one hormone can only be secreted by one tissue

true or false?

A

false, more than one tissue secretes the same hormone

248
Q

there is usually just one single target cell type for a single hormone

true or false?

A

false, more than one target cell type for a single hormone

249
Q

a single target cell can be influenced by more than one hormone

true or false?

A

true

250
Q

hormones are blood borne

true or false

A

true, but they are also neuronally derived (so false)

251
Q

some hormones are excreted from tissues that have other _____

A

functions

252
Q

chemical classification: structure, solubility, secretion, transport, and source of peptides

A
  • structure: chains of amino acids (3-500+)
  • solubility: hydrophilic
  • secretion: exocytosis
  • transport: free active peptide or precursor
  • source: pituitary, pancreas, GI tract, etc
253
Q

chemical classification: structure, solubility, secretion, transport, and source of amino acid derivatives

A
  • structure: a) catecholamines; b) thyroid hormone; c) melatonin
  • solubility: a) hydrophilic; b) hydrophobic; c) hydrophilic
  • secretion: a) exocytosis; b) endo and exocytosis; c) exocytosis
  • transport: a) 50% to carrier protein; b) most bound to carrier protein; c) 50% bound to carrier protein
  • source: a) adrenal medulla; b) thyroid gland;; c) pineal gland
254
Q

chemical classification: structure, solubility, secretion, transport, and source of steroids

A
  • structure: cholesterol derivative
  • solubility: hydrophobic
  • secretion: diffusion
  • transport: most bound to carrier proteins
  • source: adrenal and sex steroids
255
Q

_____ compounds are typically bound to carrier proteins to facilitate delivery

A

hydrophobic

256
Q

______ compounds are not always bound to carrier proteins but they can be. Why?

A

hydrophilic

  • small molecules may be subject to rapid degradation
  • half life can be very short, may not be effective by the time it reaches target organ
  • half life can be extended with carrier protein
257
Q

hormone processing

A

1) secretion, constituitive = hormone is constantly being released into circulation - regulated = only release when receiving appropriate signal (ex: pancreas and glucose)
2) binding of hormone to carrier protein (free hormones)

3) activation - can be metabolized and activated, or metabolized and inactivated
- execretion

4) inactivation - includes things like conjugation (chemical group is attached to hormone that inactivates or tag it for secretion (ex: sulfation, sulfate group is attached to steroid - this inactivated steroid makes it more water soluble)

258
Q

what are the 7 post-translational modifications of peptide hormones

A

1) peptide cleavage
2) glycosylation
3) phosphorylation
4) sulfation
5) amidation
6) acetylation
7) subunit aggregation

259
Q

examples of peptide cleavage

A

1) prepro TRH has six copies of the 3-amino acid hormone TRH

2) prohormones, such as oplomelanocortin, the prohormones for ACTH, may contain several peptide sequences with biological activity
- this hormone is cleaved into ACTH, lipotropin, endorphin

260
Q

feedback control

A

this is predominantly negative, i.e. output counteracts input, and is frequently seen in the trophic hormones
-feedback can also be positive

261
Q

thyroid stimulating hormone release from the anterior pituitary is an example of what type of feedback?

A

negative

262
Q

neuroendocrine reflexes

A

combination of neural and hormonal processes, not the same as neuromodulation
-ex: knee jerk

263
Q

neuromodulation

A

suite of neurons that regulate a variety of different behaviours

  • sleep wake cycle
  • arousal
  • reward centers
264
Q

hormone release: rhythyms

A

release of hormones is entrained to environmental cycles which vary in interval length and duration

ex: melatonin secretion peaks at night - triggered by darkness - this can adapt when changing time zones
- cortisol secretion has two prominent peaks (%pm and 11am)

265
Q

hormone delivery to the target site: carrier proteins

give examples of specific carreirs

A

can be general or specific to the hormone in question, dictating by binding affinity

ex: corticosteroid binding globulin - corticosteroids; thyroiod hormone binding globulin and transthyretin - thyroid hormones

general carrier: albumin

266
Q

how do carrier proteins help facilitate delivery of hormones to the target site?

A
  • can bind to the surface receptor
  • most of the time they bind to nuclear receptors - cause transcriptional changes, causes a genomic response at the target site (non-genomic response when binding at cell membrane, these are fast)
267
Q

which is faster, genomic or non-genomic responses?

A

genomic is much faster, these bind to nuclear receptors and cause transcriptional changes

268
Q

hormone activation

A

metabolism of the precursor or release from the carrier protein will activate the hormone that will then have a half life in the blood

269
Q

the length of time for hormone half life follows the general pattern:

A

1) single amino acid derivatives: minutes (norepinephrine, serotonin, eponephrine)
2) peptide hormones: minutes-hours (depends on the size of the hormone)
3) steroid hormones: hours (these are lipophilic, harder to destroy - it’s very expensive energy wise to make these hormones which is why they are made to last)

270
Q

3 methods of hormone inactivation

A

1) enzyme degradation: tripsin, pepsin, etc.
- these rapidly degrade hormones
- non specific, meaning they don’t have specific targets

2) hormone receptor complex endocytosis: as long as the hormone is bound to the receptor, the cell continually responds, until the endocytotic process draws the hormone into the cell, the cell no longer responds

3) conjugation: steroids are often conjugated
- sulfation
- attaching chemical groups to the steroid that makes them more water soluble, more prone to be filtered at the kidney and peed out; or tied for further degradation by other enzymes

271
Q

endocrine dysfunction: hyposecretion

A

primary or secondary, usually result in atrophy of the endocrine gland and normally treated through replacement therapy

272
Q

endocrine dysfunction: hypersecretion

A

primary or secondary, usually the result of a benign tumour (adenoma), normally treated through inhibition

273
Q

what is atrophy?

A

when the gland has shrunk, not capable of producing sufficient amounts of the hormone

274
Q

what is primary dysfunction? (endocrine dysfunction)

A

site of synthesis of the active component

  • ex: adrenal cortex not making enough cortisol
  • ex: either the anterior pituitary or hypothalamus, insufficient stimulus to stimulate cortisol release
275
Q

CRH is released from the _____

A

hypothalamus

276
Q

ACTH is released from the _____

A

anterior pituitary

277
Q

cortisol is released from the _______

A

adrenal cortex

278
Q

what does the HPA axis stand for

A

hypothalamic pituitary adrenal complex

279
Q

explain the HPA axis in simple terms

A

CRH is released from the hypothalamus, this targets the anterior pituitary (ACTH is released), this targets the adrenal cortex (cortisol is released into circulation)
-response

280
Q

how would an injection of cortisol effect the HPA axis?

A

an injection of cortisol will inhibit release of CRH from the hypothalamus and ACTH from the anterior pituitary

281
Q

endocrine dysfunction: target cell

A

lack of receptor or biochemical machinery at the target cell

-ex: hyperinsulinemia - type 1 diabetes, dysfunction at target site - inhability to maintain set point

282
Q

what are the 3 main factors that contribute to endocrine dysfunction?

A
  • hyposecretion
  • hypersecretion
  • target cell dysfunctions
283
Q

response at target cell: up and down regulation

A

receptors at the target cell are themselves regulated in response to hormone levels influencing abundance and affinity

284
Q

measurement of binding kinetics for hormone/receptor complexes relies heavily on ___?

A

the chemical law of mass action

285
Q

according to the law of mass action, if Kd is high, binding affinity is ?

A

low

286
Q

do all hormone receptor complexes adhere to the law of mass action?

A
  • non-cooperative = law of mass action upheld
  • positively cooperative = ligand binding increases receptor affinity of vacant receptors (affinity increases)
  • negatively cooperative = ligand binding decreases receptor affinity of vacant receptors (ex: insulin, insulin binds neighbouring receptors are less likely to bind insulin - to make sure there’s not an overwhelming amount of ligand binding)
287
Q

response at target cell: permissiveness

A

one hormone cannot fully exert its effect without the other being present - dual action required

288
Q

response at target cell: synergism:

A

the combined effect is greater than the sum of the parts

289
Q

what does the combination of glucagon, epinephrine, and cortisol do to the glucose levels in the blood?

A

increase significantly (over 250 mg/dl)

290
Q

what does the combination of glucagon and epinephrine do to the glucose levels in the blood?

A

slightly increases, not as much as the combination of glucagon, epinephrine, and cortisol

291
Q

response at target cell: antagonism

A

the actions of one hormone reduces the effectiveness of the second - can be direct or indirect

  • antagonism controls hypersecretion
  • agonism controls hyposecretion (sometimes hypersecretion)
292
Q

membrane bound hormone receptors

A
  • 4 priamry: ligand gated, enzyme linked, guanylyl cyclase and G-protein linked receptors
  • second messenger systems include: adenylate cyclase, guanylate cyclase, and inositol phosphate and diacyl glycerol
293
Q

nuclear hormone receptors

A

most lipophilic hormones act through nuclear receptors and many genes will have responsive elements

294
Q

explain the process of carrier protein binding to a nuclear receptor

A
  • steroid released from carrier protein, binds to cytoplasmic receptor - binds to DNA - conformational changes
  • chaperone proteins: large group = heat chock proteins (HSPs)
  • these protect receptor in cytoplasm
  • steroid receptor is therefore available for steroid to bind to
  • these HSPs increase during stressful periods
295
Q

what is another name for posterior pituitary

A

neurohypophysis, pars nervosa

296
Q

what is another name for anterior pituitary

A

adenohypophysis, pars distalis

297
Q

as a foetus, how many parts do we have to the pituitary gland?

A

3

298
Q

posterior pituitary

A

1) the hypothalamus and posterior pituitary form a neuroendocrine system with cell bodies based in the hypothalamus
2) posterior pituitary hormones synthesized in the hypothalamus
3) cell bodies then extend down the infundibulum and terminate in the posterior pituitary

299
Q

which hormones are released from the posterior pituitary?

A

oxytocin and vasopressin (predominantly but not always)

300
Q

what are the abreviations for oxytocin and vasopressin?

A

oxytocin = OT and vasopressin = AVP

301
Q

precursor peptides for OT and AVP (neurophysins) are produced int he _____

A

hypothalamus

302
Q

AVP and OT neurophysins (precursor for oxytocin and vasopressin) + proteolytic enzymes are packaged in secretory granules and begin to migrate down the axon to the ______ where the nerve terminals are located

A

neurohypophysis

303
Q

reduced ECFV (extracellular fluid volume) increases plasma osmolarity which increases osmoreceptor activity which increases which hormone from the posterior pituitary?

A

vasopressin release

304
Q

reduced ECFV (extracellular fluid volume) decreases left atrial volume which decreases arterial blood pressure which increases which hormone in the posterior pituitary?

A

vasopressin release

305
Q

what two things can lead to an increase in vasopressin release from the posterior pituitary? What is the consequence of this?

A

increase osmoreceptor activity or decreased arterial blood flow

  • increased H2O reabsorption in renal tubules
  • vasoconstriction of vascular smooth muscle
306
Q

vasopressin is an anti-diuretic hormone (reduction in urine flow rate or production)

true or false?

A

true

307
Q

which two situations cause an increase in oxytocin release?

A

birth canal distension and infant suckling

308
Q

birth canal distension causing an increase in oxytocin release is what kind of feedback loop?

A

positive - as the birth canal distends, more oxytocin is released until the baby is born

309
Q

what is the effect of an increase in oxytocin release due to infant suckling?

A

increase in uterine muscle (myometrium) contraction during parturition, increase in milk ejection from breast

310
Q

what are 3 behavioural aspects of oxytocin?

A
  • increases maternal behaviour in rats but estrogens need to be present
  • plasma OT levels increase during sexual arousal in both sexes
  • act as neuromodulators in the brain to influence social recognition, memory, and affiliative behaviours such as “pair bonding” (rodent research)
311
Q

what are 3 behavioural aspects of vasopressin release?

A
  • stimulated release of ACTH that is synergistic with CRH
  • seems to play a greater role in males rather than females in regard to social recognition and consolidation of social memory (rodent research)
  • aggression, courtship, scent making, and learning (rodent research)
312
Q

hormones released from the anterior pituitary go through the ______

A

blood supply

313
Q

what are the hormones that are released from the anterior pituitary

A

ACTH, TSH, FSH, LH, PRL, GH

314
Q

adenohypophysial cells (anterior pituitary)

A

histological and cytological methods have provided definitive evidence on the cellular source for each hormone released from the adenohypophysis

315
Q

which hormone from the anterior pituitary is a corticotroph

A

ACTH

316
Q

which hormone from the anterior pituitary is a thyrotroph

A

TSH

317
Q

which hormones from the anterior pituitary are gonadotrophs

A

FHS and LH

318
Q

which hornome from the anterior pituitary is a lactotroph

A

PRL

319
Q

which hormone from the anterior pituitary is a somatotroph

A

GH

320
Q

hormones synthesized and released from the anterior pituitary are under the control of ______ hormones that can be stimulatory or inhibitory

A

hypophysiotrophic

321
Q

name each hypophysiotropic hormone from the anterior pituitary and their associated pituitary hormone along with the final hormone produced

A

1) TRH; pituitary hormone - thyroid stimulating hormone; final hormone - TH
2) CRH; pituitary hormone - adrenocorticotropic hormone; final hormone - cortisol
3) GnRH; pituitary hormone - follicle stimulating hormone and lieutinising hormone; final hormone - estrogens and androgens
4) GHRH; pituitary hormone - growth hormone; final hormone - GH and IGF’s

322
Q

what does a release of TSH do to the body

A

-hypothalamic pituitary TSH axis

anterior pituitary releases TSH, stimulates the thyroid gland, releases T3 and T4, affects metabolic rate

323
Q

what does the release of ACTH do to the body

A

-hypothalamic pituitary ACTH axis

anterior pituitary releases ACTH, stimulates adrenal cortex, release of cortisol, affects metabolic actions

324
Q

what does the release of prolactin do to the body

A

dopamine stimulates release of prolactin from the anterior pituitary, stimulates mammary glands, breast growth and secretion

325
Q

what does a release in growth hormone do to the body

A

somatostatin stimulates the release of GH from anterior pituitary, targets the liver and/or many tissues, liver releases somatomedins which targets bone and soft tissue; other tissues target metabolic actions

326
Q

what does the release of LH and FSH do to the body

A

LH and FSH are released from the anterior pituitary, target gonads (ovaries and testies), this targets sex hormones (estrogens, progesterone, testosterone), and gamete production (ova and sperm)

327
Q

we have TSH, ACTH, LH and FSH, prolactin, and GH. Which of these are under stimulating control? which are not?

A

stimulating control means that there needs to be a stimulus to activate the release. Inhibitory control means that in order to be released, there needs to be a lack of stimulus

TSH, ACTH, LH and FSH are under stimulating control

GH’s are largely under inhibitory control (same with prolactin)

328
Q

structural characterisation of adenohypophysial hormones: GH family; growth hormone is well conserved, however there are many different variants of _____

A

prolactin

329
Q

structural characterisation of adenohypophysial hormones: GH family; what are 3 different variations of prolactin

A

mammalian prolactin (normal), cleaved prolactin, spliced variant (deletion)

330
Q

structural characterisation of adenohypophysial hormones: glycoprotein family

A

follicle stimulating hormone (FSH), leutinizing hormone (LH), thyroid stimulating hormone (TSH), human chorionic gonadotropin (hCG) - all belong to this group

-each has an alpha and a beta subunit, the amino acid sequence of the alpha subunit is similar between hormones but the beta subunit varies

331
Q

pregnancy tests use the difference in glycoprotein hormones to determine if a female has conceived or not. In these hormones, there are an alpha subunit and a beta subunit, which one differs across the glycoprotein family? which one stays the same?

A

alpha stays the same, beta varies

332
Q

Pars intermedia

A

many animals have an anatomically separate pars intermedia (sits between anterior and posterior pituitary)

  • the predominant endocrine product is alphaMSH development
  • as adults these cells are not anatomically distinct but still synthesize and secrete alphaMSH
333
Q

alphaMSH is derived from what? (what is the precursor?)

A

POMC

334
Q

POMc is a precursor for which hormones?

A

ACTH, lipoprotein, beta endorphin

-ACTH can split into alpha MSH (leads to melanin synthesis, immune response, decreased food intake)

335
Q

which enxyme cleaves POMC to create the molecules that it serves as a precursor for?

A

proconvertase

336
Q

normal growth means:

A

1) protein, fat, and cartilage synthesis
2) cell proliferation (hyperplasia and hypertrophy)
3) bone lenghtening (increased extracellular matrix)

337
Q

normal growth is influenced by:

A

1) genetic resolve
2) diet and nutrient transfer
3) disease and stress (this can be reversed regardless of when this may occur)
4) multiple layers of hormonal control (ex: growth hormones (GH; IGF’s; steroids; TH’s; Ca++ regulation)

338
Q

where do we find most of the calcium in our body?

A

in our bones

339
Q

growth rate

A

neonatal growth under influence of placental hormones growth rate varies throughout life

  • GH levels increase during puberty
  • in males, testicular androgens are very important and increase dramatically during puberty
  • adrenal androgens also increase and may be more important in females
  • testosterone and estrogen both ultimately “put the brakes on”
340
Q

____% of brain growth appears in the first two years of life

A

70

341
Q

growth hormone (GH) production is stilumated by _____ and inhibited by ______

A

GHRH, GHIH (somatostatin)

342
Q

GH is a ____ amino acid long polypeptide produced in somatotrophs

A

191

343
Q

____ is the most abundant adenohypophysial hormone (4-10% of the wet weight of the gland approx 5-10mg)

A

GH

344
Q

spontaneous secretion of GH over a 24 hour period usually peaks in the first ____ minutes of sleep

A

90

345
Q

GH is transported in _____ attached to one or more _____ (even tho it’s hydrophilic)

A

plasma, binding proteins

346
Q

the somatomedin hypothesis

A

“growth hormone does not have direct effect on growth of any given tissue but rather acts indirectly through somatomedins”

  • there are two main somatomedins - insuline like growth factors (IGF) 1 and 2 (I and II)
  • they are 70 and 67 amino acids long respectively and share many similarities with insulin
  • IGF II is 3X more abundant in adult plasma in comparison to IGF I
347
Q

where does the somatomedin hypothesis come from ?

A

Can measure bone growth through the incorporation of sulfate (in petri dish)
-add plasma - bone growth

Hypophysectomised mouse
-add plasma - no growth

Hypophysectomized mouse
-add plasma and GH (growth hormone) - growth occurs

Growth hormone is stimulating the release of an additional factors that causes bone growth
-that’s where this hypothesis comes from

348
Q

insulin and IGF receptors

A

insulin acts through and has highest affinity for its own receptor and vice versa, IGF I can bind to insulin receptors and cause an effect, but insuline tends to not bind to IGF I receptors at all

349
Q

IGF’s

A

circulating levels of IGF A increase massively during pubertal growth spurt but GH increaes moderately by comparison

  • tissue specific regulation of IGF I synthesis (related to the role that IGF is playing in regulating bone growth)
  • GH does not regulate IGF II production to the same extent (during puberty)
  • IGF II is important during fetal development and plays a role in adult growth but not to the same extent as IGF I
350
Q

what is a bone

A

bone is living tissue surrounded by an extracellular organinc matrix with a variety of cell types that have specific roles

  • compact bone is dense and used for support
  • spongy bone or trabecular bone forms a calcified lattice
351
Q

the ______ is the mature bone shaft with the _____ at either end. In a growing bone the epiphysis is separated from the diaphysis by the ______

A

disphysis, epiphysis, epiphyseal plate

352
Q

where does growth happen in a bone?

A

epiphyseal plate

353
Q

bone growth (width)

A

osteoblasts produce enzymes (osteoid) collagen and proteins to provide a framework for hydroxyapatite crystals. they deposit new bone on the outer edges of old bone to increase width. this is a dynamic process
-osteoblasts will ultimately turn into mature bone cells - osteocytes

354
Q

bone growth (length)

A

bone length growth is a different process and is regulated by cartilage cells, chondrocytes, located in the epiphyseal plates
-chondrocytes divide and multiply, lengthening the epiphysis with the older cartilage cells enlarging at the border of the diaphysis

355
Q

the dual-effector theory

A

growth of long bone is under the influence of growth hormone and the insulin like growth factors (IGF)
-in the absense of these hormones, normal bone growth does not occue

356
Q

where does abnormal bone growth happen?

A

-can happen in a variety of regions where lesions occur (increase or decrease in growth hormone)

357
Q

abnormal bone growth: lesion in anterior pituitary

A

reduction in GH, reduction of IGF = reduction of growth = hypopituitary dwarfism - extremely small population, predisposed to a lack of GH production

  • increase of release of GH, increase in IGF from liver, increase in action of IGF’s on somatic tissue (can happen2 times in life = infancy, results in genetic resolve in extremely tall people; can result in big head or big hands; can occur during adulthood (puberty or slightly after) = acromegaly
  • in infants, it’s called gigantism, in adults, it’s called acromegaly
358
Q

abnormal bone growth: lesion in the liver

A
  • liver is less responsive to growth hormone stimulation IGF-I release
  • results in Laron dwarfism
  • there are various forms of this

3 primary effectors of Laron’s Dwarfism:

  • lack of GH receptors at the liver
  • lack of IGF-I responsiveness
  • lack of GH binding carrier proteins (not enough gets to action site)
359
Q

abnormal bone growth: lesion at the end organ

A
  • reduce growth rate
  • not binding properly to end organs
  • receptors for IGF-I for example might have a mutation, lessened affinity, responsiveness is reduced
360
Q

____ - involved in energy homeostasis. hypothyroidism = reduced growth, largely permissive

A

thyroid hormones (TH)

361
Q

_____ - involved in carbohydrate metabolism. Deficiency can block growth and excess can promote growth, potential cross reactivity with IGF receptors (doesn’t tend to bind strongly to these)

A

insulin

362
Q

_____ and ____ - arrest “long-bone” length increase by closure of the epiphyseal plate (at the end of puberty, these should be at steady levels for the next 10-20 years and growth (lengthening) does not occur, only widening or narrowing)

A

androgens and estrogens

363
Q

_____ - belongs to the GH family and influences mammary gland growth as well as aspects of the immune system

A

prolactin

364
Q

______ - belongs to the GH family and influences neonatal development, metarnal glucose and amino acid supply. Peaks around mid pregnancy until full term

A

placental lactogen

365
Q

____ - nerve growth factors (NGF’s) - peripheral neurons, often used as therapeutic when people have neurodegenerative diseases such as alzheimer’s

A

neurotropic factors

366
Q

______ - red blood cell growth factor - released from kidneys, greater oxygen carrying capacity from more red blood cells

A

erythropoietin

367
Q

______ - vascular injury repair but also involved in the development of artherosclerosis - how blood vessels mature

A

platelet derived growth factors

368
Q

______ - enhances proliferation of epidermis, gut lining, pulmonary lining - epidermal growth factor released from cows saliva, promotes growth of plant

A

epidermal growth factors

369
Q

_____ angiogenesis - fibroblast growth factors (growth of blood vessels) - transforming growth factors

A

tumour derived growth factors

370
Q

what is the most tightly regulated ion in circulation?

A

Ca++

371
Q

___% of the bodies calcium is calficied structures, ____% is intracellular ___% exists in the ECF, half of this is bound to proteins or negatively charged ions and the rest is in free form Ca++

A

99, 0.9, 0.1

372
Q

up to ___% of Ca++ ions are bound to proteins so that when blood filters through kidneys, it won’t be lost (peed out), retain a lot of calcium in circulation because of this

A

60

373
Q

neuromuscular excitability - reduced calcium leads to _____ muscle contraction and high levels lead to _____ muscular contraction

A

tetanic, reduced

374
Q

stimulus secretion coupling

A

many cells will require calcium to enter the cell to stimulate the secretion of a given substance

375
Q

why regulate calcium? (5 reasons)

A

1) neuromuscular excitability
2) stimulus-secretion coupling
3) cell to cell integrity or tight junctions
4) cofactor for clotting blood
5) required for structural form of bone and teeth

376
Q

to maintain Ca++ balance, dietary intake should ___ Ca++ loss in the urine and feces

A

equal

377
Q

bone is a living tissue that is packed with _____ crystals between a collagen matrix

A

hydroxyapatite

378
Q

regulation of calcium always impacts phosphate concentrations

true or false?

A

true

379
Q

what provides strength to bones?

A

Ca++ and phosphate hydroxyapatite crystals

-if we get crystallization of these at the wrong places it can cause things like kidney stones

380
Q

bone remodelling

A

remodelling requires deposition and resorbtion

  • osteocytes
  • osteoblasts
  • osteoclasts
381
Q

osteocytes

A

mature bone cells

-have Ca++ pumps on cell membrane

382
Q

osteoblasts

A

bone builders responsible for depositing the collagen matrix

383
Q

osteoclasts

A

bone breakers

  • decrease the pH of the environment, crystlas are more likely to dissolve
  • carbonic anhydrase drives the reaction
384
Q

what are the 2 places we can get Ca++ from the bony matrix?

A
  • can be taken from bone matrix (takes longer cause we need to get calcium from crystals)
  • calcium can be taken from bone fluid space
385
Q

hormones involved in Ca++ regulation: parathyroid hormone

A
  • negative relationship between plasma [ ] and plasma [Ca++] that is extremely sensitive
  • parathyroid hormone is hypercalcaemic
  • primary job is to increase levels of Ca++
  • there is a negative relationship between the two
386
Q

hormones involved in Ca++ regulation: vitamin D3

A
  • cholecalciferol

- needs to be converted to 1.25 - (OH) - vitamin D3 (calcitriol)

387
Q

hormones involved in the regulation of Ca++: calcitonin

A
  • the ONLY hypocalcaemic hormone
  • decreases Ca++ levels in the body
  • as Ca++ goes up, calcitonin goes up and vice versa
388
Q

what is parathyroid hormones effect on bone

A

1) fast homeostatic regulation of Ca++ from bone fluid space

2) slower balancing of total body Ca++ from resorptive processes

389
Q

partahyroid hormone (PTH) _____ calcium and ____ phosphate reabsorption in the kidneys

A

increases, decreases

390
Q

parathyroid hormone (PTH)’s effect on intestines

A

actions are indirect through stimulation of vitamin D3 production

391
Q

vitamin D

A
  • considered by many as a hormone as it can be produced in the skin from 7-dehydrocholesterol
  • two important enzymatic steps that involve the sequential addition of hydroxyl groups onto the backbone of vitamin D
  • activation of 1alpha hydroxylase is the most important step and this enzyme is regulated by PTH
  • NB vitamin D is often considered a steroid therefore where does it at in the target cell? (likely acts in the nucleus, causing transcriptional change)
  • slower than non-genomic response
  • can trigger fast responses
392
Q

target site for vitamin D3

A

the gut is probably the best documented area of vitamin D3 action, where both fast and slow components are initiated

393
Q

what is the concentration of Ca++ in the lumen

A

approx 1 mM

394
Q

is the concentration of calcium higher in the lumen or in the cytosol

A

way higher in the lumen

395
Q

____ and _____ are carrier proteins inside cells that Ca++ binds to to keep constant concentration

A

calbindin and calmodulin

-vitamin D initiates response, vitamin D defficiency can cause low [ ] of Ca++

396
Q

ECaC

A

epithelial Ca++ channel = gate keeper of passive movement of Ca++ from outside to inside the cell

397
Q

what are different modes of transport of Ca++ into our out of cells?

A
  • ECaC = epithelial Ca++ channel
  • Na/Ca exchange
  • PMCA = plasma membrane calcium ATPase
  • vitamin D initiation of calmodulin and calbindin which increases transcription of ECaC
398
Q

regulation of vitamin D with PTH: hypocalcaemic event

A
  • Ca++ is lower than it should be
  • -rapid release of parathyroid hormone
    • TCH is a hypercalcemic hormone (trying to get calcium back to where it should be)
    • translocated to liver
    • attaches to backbone of D3
    • in kidney, 2 groups attached to backbone
    • PTH stimulated synthesis of alpha hydroxylase
    • 2 hormones working to promote an increase in circulating levels of Ca++
    • 2 hormones target 3 main organs (kidney - promotion of Ca++ reabsorption by parathyroid hormone; bone, promotion of calcium an d phosphate dissolution; gut - increase in vitamin D3 = increase in Ca++ uptake throughout the gut)
      • to promote Ca++ reabsorption into the blood, levels go back up to where they should be
        • Ca++ itself is negatively feeding back
        • phosphate as well - reduces the amount of available vitamin D3
399
Q

regulation of vitamin D with PTH: hypocalcaemic event

A
  • Ca++ is lower than it should be
  • -rapid release of parathyroid hormone
    • TCH is a hypercalcemic hormone (trying to get calcium back to where it should be)
    • translocated to liver
    • attaches to backbone of D3
    • in kidney, 2 groups attached to backbone
    • PTH stimulated synthesis of alpha hydroxylase
    • 2 hormones working to promote an increase in circulating levels of Ca++
    • 2 hormones target 3 main organs (kidney - promotion of Ca++ reabsorption by parathyroid hormone; bone, promotion of calcium an d phosphate dissolution; gut - increase in vitamin D3 = increase in Ca++ uptake throughout the gut)
      • to promote Ca++ reabsorption into the blood, levels go back up to where they should be
        • Ca++ itself is negatively feeding back
        • phosphate as well - reduces the amount of available vitamin D3
400
Q

calcitonin

A

not involved in day to day regulation but may be involved during the absorptive state and also during pregnancy
-calcitonin has both hypocalcaemic and hypophosphatemic effects

401
Q

when plasma Ca++ concentrations go up, this stimulates the _____ gland ___ cells and causes an increase in _____ which lowers the plasma Ca++ concentration

A

thyroid, C, calcitonin

402
Q

when plasma Ca++ concentrations go up, this stimulates the _____ gland ___ cells and causes an increase in _____ which lowers the plasma Ca++ concentration

A

thyroid, C, calcitonin

403
Q

osteoblasts are derived from ____ in the bone marrow and osteoclasts are derived from ____ in the bone marrow

A

stromal cells, macrophages

404
Q

osteoblasts are derived from ____ in the bone marrow and osteoclasts are derived from ____ in the bone marrow

A

stromal cells, macrophages

405
Q

osteoblasts and its precursor cells produce two main messengers, what are they?

A

RANKL (receptor activator of NFkB ligand) and osteopritegerin

406
Q

____ stimulates the production of osteoprotegerin

A

estradiol

407
Q

why aren’t men subject to high risk of osteoporosis like women?

A
  • androgen levels don’t tend to decline throughout the male life cycle
  • P450 aromatase is a key enzyme to make estrogen from androgen, this enzyme is always present in men
408
Q

thyroid hormones (T3 and T4)

A

tetraiodothyronine (T4) and triiodothyronine (T3) are both derived from thyroglogulin and synthesized in the follicular cells and the colloid of the thyroid gland

  • involved in the regulation of metabolic rate and are key during development (particularly development of neural tissue)
  • the basic ingredients are the amino acid tyrosine and the element iodine, tyrosine can be made in the body whereas iodine is an essential component of our diet
409
Q

thyroid hormones (T3 and T4)

A

tetraiodothyronine (T4) and triiodothyronine (T3) are both derived from thyroglogulin and synthesized in the follicular cells and the colloid of the thyroid gland

410
Q

a lot of energy is required to synthesize T3 and T4, because oft his, tyrosines are subject to recycling

true or false?

A

true

411
Q

what are 4 actions of thyroid hormones?

A

1) calorigenic: TH is the most important regulator of basal metabolic rate
2) sympathomimetic effect: action is similar to the sympathetic nervous system (increases target response to catecholamines)
3) cardiovascular: largely as a result of the increases in catecholamine receptors and calorigenic effects
4) growth: synergistic actions with both GH and IGF’s, TH is essential for normal growth and neural development

412
Q

thyroid hormone abnormalities

A
  • this is one of the more common endocrine disorders and is very prevalent in young adult women
  • includes both hypothyroidism and hyperthyroidism either of which are characterized by goiter
  • goiter is an over stimulation of the thyroid gland and not necessarily related to the capacity of the gland to synthesize and release TH
  • exophthalmos is a common feature of graves disease which is an autoimmune disease
413
Q

hypothyroidism (3 different causes)

A

cause: primary failure of the thyroid gland = decrease in T3 and T4, increase in TSH: goiter is present
cause: secondary to hypothalamic or anterior pituitary failure = decrease in T3 and T4, decrease in TRH and/or TSH: goiter is not present
cause: lack of dietary iodine = decrease in T3 and T4, increase in TSH: goiter is present

414
Q

hyperthyroidism (3 causes)

A

cause: abnormal presence of long acting thyroid stimulator (LATS) (grave’s disease) = increase in T3 and T4, decrease in TSH: goiter is present
cause: secondary to excess hypothalamic or anterior pituitary secretion = increase in T3 and T4, increase in TRH and/or TSH: goiter is present
cause: hypersecreting thyroid tumour = increase in T3 and T4, decrease in TSH: goiter is not present (occasionally this can cause inflammation of thyroid gland)

415
Q

possible symptoms of hypothyroidism

A
  • low BMR
  • decreased perspiration
  • slow pulse
  • lowered body temperature
  • cold intolerance
  • lethargy, tiredness
  • weight gain
  • loss of hair
  • edema of face and eyelids
  • menstrual irregularities
  • goiter (may or may not be present)
416
Q

possible symptoms of hyperthyroidism

A
  • elevated BMR
  • increase perspiration
  • rapid pulse
  • increase body temperature
  • heat intolerance
  • nervouseness and anxiety
  • weight loss
  • muscle wasting
  • increased appetite
  • exophthalmos (sometimes)
  • goiter (primary or secondary origin)
417
Q

melatonin

A

primary hormone released from the pineal gland and is synthesized from the amino acid tryptophan (acts as a neurotransmitter as well)

  • synthesized and released in a rhythmical fashion that is closely related to circadian rhythms - scotophase (dark) and photophase (light)
  • darkness is a universal stimulation for the synthesis and release of melatonin from the pineal gland suggesting a strong link between the pineal and the optic tract
418
Q

what is the link between the pineal gland and the optic tract?

A

the link comes from the suprachiasmic nucleus (SCN) which is our major biological clock where the interaction between PER genes and CLOCK proteins cycle at a remarkably constant rate that shifts depending on light cues

419
Q

there is an inhibition of the pineal gland during _____

A

phosphotase (light)

420
Q

reproduction follows cycles, so there is a link between _____, sex hormones, and reproduction

A

melatonin

421
Q

the adrenal gland sits on top of which structure?

A

kidney

422
Q

the adrenal gland has three layers to its cortex, what aret hese layers and which steroids do they each produce

A

inner layer: zona reticularis - adrenal androgens (primary = DHEA)

middle layer: zona fasiculata - glutocorticoids (main one that we produce is cortisol)

outer layer: zona glomerulosa - mineralocorticoids (involved in mineral balance, increases in Na+ and K+)

423
Q

adrenal hormones

A

Adrenal steroids released from the adrenal cortex:

  • mineralocorticoids: aldosterone
  • gluticocorticoids: cortisol
  • sex hormones: dehydroepiandrosterone androstenedione (androgens) and estrogens

Catecholamines released from the adrenal medulla:

  • epinephrine (80%)
  • norepinephrine (20%)
424
Q

cholesterol as a precursor for steroid synthesis

A
  • composed of 4 main loops with an extension on loop D
  • P450 side chain cleavage (sits on inner mitochondrial membrane)
  • huge impact on steroid synthesis
425
Q

three main “parent” molecules of cholesterol

A

C21 - pregane (base of progesterone)

C19 - androstane (bases of androgens)

C18 - estrane (base of estrogens)

426
Q

adrenocorticosteroids

A

1) gluticocorticoids: corticosteron - precursor for cortisol

2) mineralocorticoids - aldosterone (precursor is corticosterone)

427
Q

sex steroids

A

1) androgens: DHEA is precursor for androstenedione which is the precursor for testosterone, which is the precursor for DHT
2) estrogens: estrone (made from androstenedione with the help of aromatase), estradiol (made from testosterone with the help of aromatase), estriol (made from estradiol)

428
Q

mineralcorticoid

A
  • aldosterone acts on the distal and collecting tubules of the nephron in the kidney to promote Na+ reabsorption and inhibit K+ reabsorption (there are very few life sustaining hormones but this is one of them, if you lack the ability to synthesize aldosterone you will die)
  • regulates body fluid volume which has implications on the renal and cardiovascular systems
  • secretion is regulated by the renin angiotensin system and also directly by circulating K+ [ ] . aldosterone regulation is largely independent of the pituitary gland
  • hyperaldosteronism can be either primary (Conn’s syndrome) or secondary. symptoms present as hypernatremia, hypokalemia, and usually hypertension
429
Q

why are estrogens considered female sex steroids and androgens considered male sex steroids?

A

-in females, there’s a higher concentration of estrogen and in males more androgens

430
Q

dehydroepiandrosterone (DHEA)

A
  • the adrenal gland produces small amounts of both (estrogens and androgens) as DHEA is an adrenal androgen (in females this is important in directing development, major source of adrenal androgens in females)
  • in males, testosterone overpowers the actions of DHEA, however as females otherwise lack androgens DHEA plaus a role in the pubertal growth spurt, hair growth and the female sex drive
431
Q

adrenogenital syndrome

A

symptoms are dependent on sex and age of hyperactivity onset

  • adult females: masculinisation, facial hair,, deepening of voice, etc.
  • newborn females: psuedohermaphrodism (females with male parts)
  • adult males: no effect
  • pubertal males: precocious pseudopuberty (individual develops secondary sexual characteristics but is not fertile)
432
Q

glucocorticoid release

A
  • triggered by stress or diurnal rhythm
  • targets the hypothalamus which releases CRH
  • CRH targets teha ntrior pituitary which releases ACTH
  • targets adrenal cortex which releases cortisol
  • results in an increase in blood glucose (by stimulating glucogenesis and inhibiting glucose uptake)
  • increase in blood amino acids (by stimulating protein degradation)
  • increase in blood fatty acids (by stimulating lipolysis)
433
Q

what are the direct action of glucocorticoids

A
  • stimulates gluconeogenesis - generation of glucose from non-carbohydrate substrates (amino acids, pyruvates, glycerol)
  • inhibits glucose uptake by many peripheral tissues
  • stimulates protein degradation in muscle
  • stimulated lipolysis, mobilising fatty acids as an alternative energy source
434
Q

what are the permissive actions of glucocorticoids

A

-vascular collapse during stressful events in the absense of glucocorticoids

435
Q

what are the anti-inflammatory and immunosuppresive actions of glucocorticoids

A
  • the anti-inflammatory effects are seen following administration of supra physiologic or pharmacologic levels
  • prevention of leucocytes infiltration into the wound site
  • atrophy of lymphatic system
436
Q

cortisol hypersecretion

A

Cushings syndrome (hypersecretion), caused by:

  • increased amounts of CRG or ACTH
  • adrenal tumours
  • ectopic ACTH release

symptoms include:

  • excess glucose (coining the term adrenal diabetes)
  • fat deposition in the face and abdomen, thin legs and arms
  • facial hair excess
437
Q

cortisol hyposecretion

A

Addison’s disease (hyposecretion)

  • general name for bilateral damage to the adrenals
  • can also be primary or secondary in nature

symptoms include:

  • increased integument pigmentation
  • weakness, weight loss, hypotension, salt craving (because this enhances salt reabsorption) and hypoglycemia
438
Q

general adaptation to stress: primary alarm response

A
  • catecholamine surge into the system
  • increase in BMR
  • increase in blood flow to required organs
  • hepatic glycogenolysis

-mobilizing energy reserves immediately

439
Q

general adaptation to stress: secondary resistance response

A
  • described actions of cortisol on metabolism
  • continued mobilization of glucose for central organs
  • continued breakdown of alternative energy stores (lipids and proteins)
440
Q

general adaptation to stress: tertiary exhaustion response

A
  • muscle wasting, hyperglycemia (diabetes mellitus)
  • atrophy of the immune system
  • vascular derangements

could be maladaptation to exposure of chronic stress
-this stage only comes int play in this situation

441
Q

the adrenal medulla

A

-essentially acts as an extension of the sympathetic nervous system

442
Q

catecholamine release from the adrenal medulla is largely under the control of the ____

A

SNS

443
Q

both catecholamines are sotred in ____ granules

A

chromaffin

444
Q

both catecholamines are the active ligands in the adrenergic system and they will bind to one of the 4 adrenergic receptors, what are they?

A

alpha 1 and 2, beta 1 and 2

445
Q

physiological effect of epinephrine

A
  • rapid mobilization of the bodies energy reserves
  • increase cardiac output and total peripheral resistance
  • increase coronary and skeletal muscle anteriolar dilation
  • reduce gut motility
  • increases glycogenolysis in liver and muscle
  • increased CNS alterness
  • dilates pupils and flattens the lens
  • increases sweating
446
Q

adrenoceptors: alpha 1

A
  • most sympathetic target cells
  • ligand affinity is higher in norepinephrine than epinephrine
  • 2nd messenger = PLC
  • ex: generalized anterior vasoconstriction
447
Q

adrenoceptors: alpha 2

A
  • digestive system
  • ligand affinity higher in norepinephrine than epinephrine
  • 2nd messenger: decreased cAMP
  • ex: decreased motility in digestive tract
448
Q

adrenoceptors: beta 1

A
  • heart and kidney
  • ligand affinity is equal in epineprhine and norepinephrine
  • 2nd messenger: increase in cAMP
  • ex: inotropic and chronotropic actions
449
Q

adrenoceptors: beta 2

A
  • skeletal and smoothe muscle in some blood vessels and organs
  • ligand affinity is higher in epinephrine than norepinephrine
  • 2nd messenger = increase in cAMP
  • ex: glycogen breakdown in skeletal muscle bronchiolar dilation and smooth muscle dilation in blood vessels nin the heart
450
Q

adrenoceptors: beta 3

A
  • adipose tissue
  • ligand affinity is higher in norepinephrine than epinephrine
  • 2nd messenger = increase in cAMP
  • ex: mobilises lipids for subsequent catabolism
451
Q

all adrenoreceptors are g-protein coupled receptors

true or false?

A

true

452
Q

epinephrine reversal

A

epinephrine can bind to different isoforms of the adrenergic receptor, causing completely different response (vasodilation vs vasoconstriction)

  • this is due to numerous agonists/antagonists for adrenoreceptors
  • phenylephrine is an antagonist specific for the alpha adrenoceptor, when it is blocked, epinephrine will bind to the beta receptor and cause the opposite response
453
Q

a stressor targets the ____ which causes an increase in CRH, which then targets the ______ and causes an increase in ACTH (from precursor peptide POMC) which then targets the _____ and releases cortisol

A

hypothalamus, anterior pituitary, adrenal cortex

454
Q

a stressor targets the hypothalamus, which activates the ______. it then stimulates the adrenal medulla which causes an increase in ______. This will target the endocrine pancreas (which increases glucagon release and decreases insulin release) or the ______ (this leads to vasoconstriction, decrease in renal blood flow, and increase in renin, angiotensin, and aldosterone).

A

sympathetic nervous system, epinephrine, arteriolar smooth muscle

455
Q

islets of langerhans and pancreatic hormones

A
  • insulin and amylin: released from beta cells (10:1 ratio)
    0glucagon: released from alpha cells
  • somatostatin: released from D or ? cells (weird s shape thing)
  • pancreatic polypeptides: released from PP or F cells

-all these hormones are involved in regulating fuel metabolism and all act at multiple levels

456
Q

amylin

A
  • released with insulin following a meal

- slows down the appearance of glucose in blood

457
Q

somatostatin

A
  • released in response to increased glucose and amino acid levels
  • D cells are always found in close association with alpha and beta cells (suggests paracrine role for somatostatin, regulating release of insulin and/or glucagon
  • inhibits digestive and absorptive processes
458
Q

pancreatic polypeptide

A
  • dramatic postprandial increase in plasma PP
  • PP levels suppress SST levels and vice cersa
  • D and F cells may be regulating each other (as well as alpha and beta cells)
459
Q

explain the glucose activation of insulin secretion from pancreatic beta cells after an increase in extracellular glucose

A
  • this increase inititaes a series of events within the cell
  • increase in ATP production within beta cells
  • this inhibits K+ATPase channels
  • this changes resting membrane potential
  • results in L-type Ca++ channels opening, allowing Ca++ to flood into the cell
  • Ca++ can do many things as a second messenger (one is to promote exocytocic release)
  • enhances glucose uptake by cells
460
Q

fuel metabolism: fuel

A

carbohydrates, fats, proteins

461
Q

fuel metabolism: metabolism

A

a generalist term for the chemical reactions that occur in the body

462
Q

fuel metabolism: anabolism

A

the required energy input (ATP) and is the synthesis of larger macromolecules either for function or energy storage

463
Q

fuel metabolism: catabolism

A
  • breakdown of macromolecules
  • ex: hydrolysisL glycogen broken down to glucose
  • ex: oxidation: glucose broken down to ATP
464
Q

the balance between anabolism and catabolism is not always straight forward. what are some exceptions?

A
  • growth periods
  • short and long term “gaps” in food intake
  • absorptive (fed) and post-absorptive (fasted) states
465
Q

what causes glucose levels to go up?

A
  • glucose absorption from digestive tract
  • hepatic glucose production
    a) glycongenolysis
    b) gluconeogenesis
466
Q

what causes glucose levels to go down?

A
  • transport of glucose into the cells
    a) energy production
    b) energy storage
  • urinary excretion of glucose
467
Q

proinsulin is made of what

A

C-peptide (connecting peptide) and insulin (A chain and B chain)

468
Q

insulin - carbohydrates : facilitates glucose transport

A

facilitate glucose transport

  • glucose cannot simply diffuse into cells it is transported by a family of proteins known as GLUT or by Na+ glucose co-transport
  • GLUT-4 transports most of the circulating glucose during the absorptive state into skeletal muscle and adipose tissue
  • GLUT-4 are housed in intracellular vesicles and are recruited onto the cell membrane in response to insulin
  • in the post absorptive state glucose is transported out of the hepatocyte by GLUT-2 transporters
  • in the absorptive state insulin facilitates conversion of glucose into glucose 6-phosphate to keep intracellular concentrations low
469
Q

in the absense of insulin, there are no ____ transporter in the membrane

A

GLUT-4

470
Q

in the fed state, insulin signals the cell to insert ____ transporters into the membrane, allowing glucose to enter the cell

A

GLUT-4

471
Q

in the fasted state, the hepatocyte makes glucose and transports itout into the blood, using ____ transporters

A

GLUT-2

472
Q

in the fed state, the glucose concentration gradient ______ and glucose enters the hepatocyte

A

reverses

473
Q

insulin - carbohydrates: inhibits glycogenolysis in the liver

A
  • favoring carbohydrate storage

- hypoglycemic hormone = job to ensure that there is sufficient energy stored in your system

474
Q

insulin - carbohydrates: inhibits gluconeogenesis

A

-reduces circulating amino acids

475
Q

insulins action on fat

A
  • inhibits lipolysis
  • stimulates fatty acid uptake in adipose tissue
  • stimulates glucose uptake and conversion to triglycerides

all of these actions promote removal of fatty acids and glucose from the blood and storage in adipose tissue

476
Q

insulins action on protein

A
  • promotes amino acid uptake
  • stimulates protein synthesis
  • inhibits protein degradation
477
Q

insulin as the ONLY hypoglycemic hormone

A
  • there is a positive relationship between blood glucose and amino acid concentrations and insulin concentration
  • feed forward regulation by glucagon-like peptide-1 and gastric inhibitory peptide (anticipatory response when you’re about to eat)
478
Q

diabetes mellitus

A

-likely the most common endocrine disorder in the western world, literally means “honey running through”

479
Q

type 1 insulin-dependent diabetes

A

lack of insulin secretion

-normally seen in children and represents a small proportion of diabetics (normally genetically based)

480
Q

type 2 or non-insulin-dependent diabetes

A

lack of insulin sensitivity

-the most common form and invariably seen alongside obesity (80-90%)

481
Q

insulin deficiency can cause what 6 things?

A

1) increase in hepatic glucose output
2) decrease in glucose uptake by cells
3) decreased triglyceride synthesis
4) increased lipolysis
5) decreased amino acid uptake by cells
6) increased protein degradation

482
Q

explain the process of an increase in hepatic glucose output due to insulin deficiency

A

this causes hyperglycemia, glucosuria (increase in glucose in urine), osmotic diuresis (peeing a lot, get dehydrated), polyuria, dehydration (which leads to polydipsia or cell shrinkage), decrease in blood volume, peripheral circulatory failure (which leads to renal failure and death)

483
Q

explain the process of a decrease in glucose uptake by cells due to insulin deficiency

A

this causes either hyperglycemia (and following this, all the symptoms associated with this), or intracellular glucose deficiency, which leads to polyphagia (lots of eating)

484
Q

explain the process of a decrease in triglyceride synthesis or lipolysis due to an insulin deficiency

A

this leads to increase in blood fatty acids, alternative energy source utilisation, ketosis (ketone bodies in circulation - sweet smell in breath), metabolic acidosis (which leads to increased ventilation or diabetic coma which can lead to insulin shock), which leads to death

485
Q

explain the process of a decrease in amino acid uptake by cells due to a deficiency of insulin

A

this can cause an increase in blood amino acids, increase in gluconeogenesis, aggravation of hyperglycemia, which leads to the following symptoms associated witht his

486
Q

explain the process of an increase in protein degradation due to insulin deficiency

A

this can cause an increase in blood amino acids (and following symptoms) or muscle wasting which leads to weight loss

487
Q

what is glucagon’s relationship with blood glucose levels

A

there is a negative relationship b etween blood glucose levels and glucagon

488
Q

what is glucagon’s relationship with carbohydrates

A

carbohydrates stimulate hepatic glycogenolysis and gluconeogenesis (promoting the liberation of glucose into the circulation)

489
Q

what is fats relationship with glucagon

A
  • glucagon promotes fat breakdown (lipolysis) and increase release of TG, DG and MG lipase’s from fats
  • inhibits hepatic ketogenesis reducing FFA conversion to ketone bodies
490
Q

what are proteins relationship with glucagon

A

-glucagon promotes hepatic protein catabolism (trying to liberate energy sources)

491
Q

glucagon acts in the opposite way as insulin

true or false?

A

true

492
Q

feasting and fasting actions of insulin and glucagon

A

pancreatic alpha and beta cells respond in the opposite direction to sugars and fats in the blood but in the same direction in response to amino acids

-after eating a high protein meal, there’s an increase in blood amino acid concentration

beta cells: cause a increase in insulin, which promotes cellular uptake and assimilation of amino acids; increase in glucose uptake by cells which causes hypoglycemia; decrease in hepatic glucose output which causes hypoglycemia
(blood glucose remains normal)

alpha cells: cause an increase in glucagon, which causes an increase in hepatic glucose output, which leads to hyperglycemia
(blood glucose remains normal)

the actions of these balance eachother out