Exam #2 Flashcards
(492 cards)
1
Q
the peripheral nervous system is comprised of both the ______ division and the ____ division
A
afferent, efferent
2
Q
the afferent division of the peripheral nervous system contains ___ stimuli and ____ stimuli
A
sensory, visceral
3
Q
the efferent division of the peripheral nervous system is comprised of the _____ nervous system and the ____ nervous system
A
somatic, autonomic
4
Q
the somatic nervous system controls _____ neurons, which controls ______
A
motor, skeletal
5
Q
the autonomic nervous system has 2 branches, what are they?
A
sympathetic and parasympathetic
6
Q
both the sympathetic and the parasympathetic nervous systems control _____ muscle, _____ muscle, and ____
A
smooth, cardiac, glands
7
Q
the autonomic nervous system innervates organs whose functions are not usually what?
A
under voluntary control
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
9
Q
sensory information from the autonomic nervous system may be processed within which 3 structures
A
- hypothalamus
- limbic system
- spinal cord
10
Q
what are the 2 effectors of the autonomic nervous system
A
visceral organs and blood vessels (also glands)
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
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
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)
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)
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
16
Q
what is a ganglion
A
a mass or a group of neuronal cell bodies that form a knot-like mass of tissue
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
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
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
20
Q
in the sympathetic division of the autonomic nervous system, preganglionic fibers release _____ whereas most postganglionic fibers release _____
A
acetylcholine (ACh), norepinephrine (NE)
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
22
Q
sympathetic neurons secrete ___% epinephrine and ___% norepinephrine
A
85, 15
23
Q
in the parasympathetic division of the autonomic nervous system, fibers originate from the _____
A
cranial and sacral areas of the CNS
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
25
in the parasympathetic division of the autonomic nervous system, the preganglionic fibers release ____ whereas the postganglionic fibers release ____
both acetylcholine (ACh)
26
both in the sympathetic and parasympathetic nervous systems does each postganglionic neuron receive synapses from many preganglionic cells (convergence)
True or False?
true
27
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?
false, this only happens in the SNS, the rate of the PNS is 1:4 (lower than SNS)
28
the sympathetic nervous system tends to respond as a unit
True or False?
true
29
the parasympathetic nervous system tends to respond as a unit
true or false?
false, in the parasympathetic nervous system, things like heart rate can be regulated independently of gut or liver, there's enough individual control
30
4 of the cranial nerves have parasympathetic function, which are they?
- 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
31
what are some characteristics of the vagus nerve?
- 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
32
the ____ nerve carries sensory information from most of the viscera
vagus
33
what is the reflex arc of the vagus nerve?
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
34
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
nicotinic, muscarinic
*in the parasympathetic division, sometimes the receptors between the postganglionic cell and target cell are nicotinic
35
which tends to have longer lasting effects: the sympathetic branch of the autonomic nervous system or the parasympathetic branch
sympathetic branch
36
why does the sympathetic nervous system tend to have a longer lasting effect than the parasympathetic nervous system?
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)
37
which receptors can we find on the target organs of the sympathetic nervous system (NE)?
(hint: "p-dibi")
- a1 receptors (phospholipase c)
- a2 (decreae cAMP)
- B1 (increase cAMP)
- B2 (both increase and decrease cAMP)
- B3 (increase cAMP)
38
which receptors can we find on target organs in the parasympathetic nervous system (ACh)?
-nicotinic AChR (ligand gated ion channel)
- muscarinic AChR (GPCR):
- M1 (phospholipase c)
- M2 (decrease cAMP)
- M3 (phospholipase c)
39
the sympathetic nervous system activates the ______ to release massive amounts of _____. This second messenger signalling often affects what?
adrenal medulla, epinephrine, ion channels
40
what are the effects of the sympathetic nervous system stimulation on the heart?
increased rate, increased force of contraction (of whole heart)
41
what are the effects of the parasympathetic nervous system stimulation on the heart?
decreased rate, decreased force of contraction (of atria only)
42
what are the effects of the sympathetic nervous system stimulation on the eye?
dilation of pupil
43
what are the effects of the parasympathetic nervous system stimulation on the eye?
constriction of pupil
44
what are the effects of the sympathetic nervous system stimulation on the exocrine pancreas?
inhibition of pancreatic exocrine secretion
45
what are the effects of the parasympathetic nervous system stimulation on the exocrine pancreas?
stimulation of pancreatic exocrine secretion (important for digestion)
46
what are the effects of the sympathetic nervous system stimulation on the salivary glands?
stimulation of small volume of thick saliva rich in mucus
47
what are the effects of the parasympathetic nervous system activation on the salivary glands?
stimulation of large volume of watery saliva rich in enzymes
48
the exocrine pancreas produces which enzymes?
trypsin, pancreatic lipase, and pancreatic amylase
49
what is dual innervation?
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)
50
the effects of dual innervation are usually antagonistic
True or False?
false, the effects can be antagonistic or complimentary
51
what are some examples of the antagonistic functions of dual innervation?
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
52
give examples of the complimentary functions of dual innervation
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)
53
not all target organs are subject to dual innervation. Which target organs are only innervated by the sympathetic branch?
adrenal medulla, sweat glands, smooth muscle of most blood vessels
54
what are the central nervous system centres that contribute to autonomic regulation?
- 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)
55
look at figs. 12.3, 12.4, 12.5, 12.8, 12.9, 12.10
page #?
| -somewhere between 371-394 or 378-398
56
what are the 3 types of muscle?
- 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)
57
which of the 3 types of muscle is multinucleated?
skeletal muscle
58
which of the 3 muscle types is not striated?
smooth muscle
59
which of the 3 types of muscle is stacked end to end?
cardiac muscle
60
which of the 3 types of muscle is compared to an intercalated disc?
cardiac muscle
61
controlled muscle contraction allows for 3 things, what are these things?
- 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
62
skeletal muscle is controlled by which division of the nervous system? (central or peripheral)
CNS
63
the neurons in skeletal muscle have a cell body in the motor cortex synapse on motor neurons in the _____
spinal cord
64
skeletal muscle: motor neurons with cell bodies in the spinal cord send axons to synapse onto _____
muscle cells (nerve muscle synapse is called a neuromuscular junction (NMJ)
65
the group of muscle cells controlled by a motor neuron is a _____
motor unit
66
___% of axons cross through the medullary pyramids
95
67
in mammals, each muscle cell receives how many synapses?
only one
68
muscles that require fine control have very ______ convergence
ex: muscles of the eye
little
69
muscles that don't require fine control can have very _____ convergence
ex: rectus femoris
high
70
in mammals, inhibitory synapses on muscle cells are quite frequent
true or false?
false, in mammals, inhibitory synapses on muscle cells do not exist
71
what is the size comparison of an neuromuscular junction synapse (NMJ) compared to a central synapse?
NMJ = 1000 um (squared)
central synapse = 0.05 um (squared)
72
why is the NMJ such a huge synapse?
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)
73
what is the structure of a skeletal muscle?
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
74
what is the fluid inside the T-tubules of a skeletal muscle cell?
ECF
75
the T-tubules are a continuation of what?
the cell membrane has holes that lead to the T-tubules
76
the sarcoplasmic reticulum is full of what?
Ca++
77
what determines the length of one sarcomere
from z disc to z disc
78
what is the name of the line in the center of the sarcomere
m-line
79
what is the a-band in a sarcomere
sits between the z discs
80
what is a z disk in a sarcomere
sits between a-bands
81
the thick filaments are in the _____ of a sarcomere and the thin filaments are _____
middle, towards the edges
82
what are the 3 components of the myofibril
actin, myosin, and titin
83
what is the major component of a thick filament?
myosin
84
myosin
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
85
what is the orientation of the heads and tails of a myosin molecule?
tails are oriented towards the center of the filament and globular heads protrude outward at regular intervals
86
which part of the myosin filament forms cross bridges between thick and thin filaments?
myosin heads
87
myosin has two important sites that are critical to contractile process, what are they?
- an actin binding site
| - a myosin ATPase
88
what is a cross bridge in muscle fiber contractile unit
cross bridge refers to the interaction between myosin and actin molecules (the interaction itself is called a cross bridge)
89
the thick filaments of a muscle contractile unit are made of _____, whereas the thin filaments are made of ____
myosin; actin, tropomyosin, troponin, nebulin, titin
90
primary structural component of thin filaments
actin
91
what are the spherical monomers that assemble into long chains in the actin chain
g-actin monomers
92
each actin molecule has a special binding site for attachment with the _____
myosin head
93
the binding of a myosin head to an actin monomer results in what?
contraction of the muscle fiber
| -this interaction is key to produce movement
94
topomyosin
- regulatory protein
- thread-like molecules alongside the groove of the actin spiral
- tropomyosin covers the myosin binding sites
95
which regulatory protein covers the myosin binding sites on the actin molecules?
tropomyosin
96
troponin is made of 3 polypeptide units, what do they bind to?
- one binds to tropomyosin
- one binds to actin
- one binds with Ca++
97
what effects do Ca++ levels have on the effects of troponin on tropomyosin?
- 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
98
describe the action of troponin on muscle contraction
- 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
99
titin
- structural protein
- giant elastic protein (one of the biggest in mammalian genome)
- joins m-lines to z-lines at opposite ends of the sarcomere
100
what are the 2 important roles of titin?
- help stabilize position of thick filaments in relation to thin filaments
- improves muscle's elasticity
101
nebulin
aligns actin filaments
102
the muscle ______ when actin and myosin slide past each other
shortens
103
when a muscle contracts, the A-band gets smaller along with the length of the filaments
true or false?
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
104
what structures shorten when a muscle contracts?
the H-zone and the I-band both shorten
105
what is the role of Ca++ in a muscle cell to be able to generate tension?
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
106
what initiates the contraction of a muscle cell?
Ca++
107
in its relaxed state, the myosin head is ______, and ______ partially blocks the binding site on actin, myosin is weakly bound to actin
cocked, tropomyosin
108
power stroke
cross bridge bends, pulling thin myofilament inward
109
the phase of muscle cell contraction where the cross bridge detaches at the end of the power stroke and returns to its original conformation
detachment
110
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
c, d, a, b
111
actin and myosin contract along with the contraction of a muscle cell
true or false?
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
112
what is a motor protein?
a protein that hydrolyzes ATP to convert chemical energy to carry out mechanical work
ex: myosin
113
look at fig 12.9 and remember cycle
p.?
114
explain the 4 steps of the contraction cycle of a muscle cell
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
115
the sarcoplasmic reticulum is closely related to the T-tubules and has a high [ ] of Ca++
true or false?
true
116
how does the sarcoplasmic reticulum have such a high [ ] of Ca++?
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++]
117
T-tubules run ______ from the surface of the muscle cell membrane into central portions of the muscle fiber
perpendicular
118
T-tubules are aligned on the edges of the ____-band
A
| thick filaments, myosin
119
an action potential on the surface of a membrane also invade T-tubules
true or false?
true
120
what is the effect of the spread of an action potential down a T-tubule on the sarcoplasmic reticulum?
- 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
121
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
directly, indirectly, foot
122
the opening of the ryanodine receptor on the sarcoplasmic reticulum allows a massive flood of Ca++ into the cytoplasm via _____
because of the [ ] gradient
123
what are the two purposes of the voltage gated Ca++ channel (dihydropyridine receptor) in the T-tubules?
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)
124
thinking about what we've learned in the whole semester, explain the process of initiation of muscle action potential and excitation contraction coupling
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
125
rigor mortis
- 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
126
explain the process that leads to the relaxation of a muscle
- 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)
127
what is myasthenia gravis
- 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
128
what are common symptoms of myasthenia gravis?
- 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
129
what are some treatments for myasthenia gravis?
- 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)
130
what are the contraction-relaxation steps that require ATP
- 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
131
what are the 3 energy sources for muscle contraction?
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)
132
creatine phosphate
- 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)
133
how does creatine phosphate work?
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
134
oxidative phosphorylation
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
135
glycolysis
- 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
136
what causes muscle fatigue?
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***
137
the action potential and the contraction of a skeletal muscle happen almost simultaneously
true or false?
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)
138
the total amount of tension generate by s skeletal muscle is dependent on the _____ of the motor neuron
firing frequency
-can be single twitch or summation
139
what is the difference between unfused tetanus and complete tetanus in a skeletal muscle?
complete tetanus is not able to generate the peak amount of tension that the unfused tetanus can reach
140
in _____ tetanus, fatigue causes the muscle to lose tension despite continuing stimuli
complete
141
what are 2 different views on what leads a muscle to reach its peak amount of tension?
- 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
142
takes several AP to cause generation of maximal tension
true or false
true
143
if there is less overlap between the thick and thin filaments, what effects does this have on a muscle's ability to generate tension?
this reduces the number of possible interaction sites, lessening tension
144
by providing more overlap between the thick and thin filaments, what effects does this have on a muscle's ability to generate tension?
- 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
145
what are the 3 types of motor units found in most mammals
- slow twitch oxidative (red muscle)
- fast twitch oxidative-glycolytic (red muscle)
- fast twitch glycolytic (white muscle)
146
in turkey, muscle fiber groups are ____, whereas in mammals, muscle fiber groups are _____
together, interspersed
147
slow twitch oxidative motor unit (slow fatigue resistant)
- 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
148
fast twitch oxidative-glycolytic (fast fatigue resistant)
- generate a lot of tension, moderately fast
- somewhat resistant to fatigue
- moderate number of mitochondria
- fibres are larger than slow twitch muscles
149
fast twitch glycolytic (fast fatiguable)
- white muscle
- generate the most tension
- fatigue rapidly
- few mitochondria (anaerobic catabolism)
- fibres are larger than slow twitch
150
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
25, 50
151
one muscle may have many motor units of different fiber types
true or false?
true
152
what are the first motor units recruited?
- 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
153
what are the 2nd motor units recruited?
- motor units that include fast fatigue resistant fibres
| - these motor neurons are slightly larger
154
what are the 3rd and last motor units recruited?
- fast fatiguable (=fast twitch glycolytic, white muscle)
| - the largest motor unit, includes most fibres
155
what is the size principle in the recruitment of motor units?
slow twitch is activated first (smallest), then fast fatigue resistant, then fast fatigable (largest)
156
one motor neuron can innervate more than one type of muscle
true or false?
false
157
general characteristics of cardiac muscle cells
- interconnected by intercalated discs and form functional syncytia
- within intercalated discs there are two kinds of membrane junctions (desmosomes and gap junctions)
158
what are the 3 types of cardiac muscle cells
1) myocardial autorhythmic cells
2) myocardial contractile cells (working cells)
3) conducting cells
159
cardiac muscle: myocardial autorhythmic cells
- initiate and maintain electrical activity in the heart (generate their own action potentials without electrical stimulus)
- do not contract
- have gap junctions
160
cardiac muscle: myocardial contractile cells (working cells)
- 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
161
cardiac muscle: conducting cells
- carry electrical signals from the pacemakers to the contractile cells
- gap junctions
162
where does the cardiac impulse originate?
at the SA node (sinal atrial node)
163
explain the process of electrical conduction in the heart
- 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
164
what kind of cells initiate action potentials in cardiac cells?
autorhythmic cells
165
what is the resting membrane potential of a cardiac muscle cell?
there is no real resting membrane potential, it is rather a spontaneous conduction of action potentials by the autorhythmic cells
166
what is the pacemaker potential
membrane slowly depolarizes "drifts" to threshold, initiate action potential, membrane repolarizes to -60 mV (cardiac cell)
167
autorhythmic cells: I(f)
a Na+ current
168
autorhythmic cells: ICa(T)
fast calcium current
169
autorhythmic cells: ICa(L)
slow Ca++ current
170
in a skeletal muscle cell, ____ flows inside the cell during an action potential, in a cardiac muscle cell, ____ is used instead
Na+, Ca++
171
explain the steps of an action potential in contractile cells of a cardiac muscle
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)
172
why is the repolarization phase of cardiac contraction cells so long?
- plateau is primarily due to the activation of slow L-type Ca++ channels
- this long action potential ensures adequate ejection of blood
173
how does the long action potential of contractile cells avoid tetanus?
long AP causes long refractory period and long contraction
| -this refractory period overlaps the tension curve
174
refractory period of skeletal vs cardiac muscle cell
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
175
excitation-contraction coupling in cardiac contractile cells
-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
176
smooth muscle
- 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
177
what is the speed of contraction of smooth muscle relative to other muscle types?
contracts and relaxes much more slowly
178
what is the energy expenditure of a smooth muscle relative to other muscles?
uses less energy skeletal or cardiac muscle
179
_____ muscle sustains contraction for extended periods of time
smooth
180
_____ muscles are the slowest to contract and to relax
smooth (and then skeletal and then cardiac)
181
what are the 3 ways we can classify smooth muscle?
- 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)
182
phasic smooth muscles can either be ______ (ex: esophagus) or can work in cycles between _____ and ______ (ex: intestine)
relaxed, contraction, relaxation
183
tonic smooth muscles can either be contracted and release when needed (ex: sphincter) , or can ________ as needed (vascular smooth muscle)
vary as needed, but contraction is always happening
184
smooth muscle classification: communication with neighbouring cells
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)
185
smooth muscle is arranged in sarcomeres
true or false?
false
186
what kind of signal is needed to initiate contraction of a smooth muscle cell?
electrical, chemical, or both
187
smooth muscle cells are controlled by the ____ nervou system
autonomic
188
smooth muscle cells have very specialized receptor regions on their post-synaptic membranes
true or false?
false, smooth muscle cells lack specialized receptor regions, they have neurotransmitter receptors dispersed all over the cell membrane
189
in smooth muscle ____ is from the extracellular fluid and sarcoplasmic reticulum
Ca++
190
in smooth muscle, ____ initiates a cascade ending with phosphorylation of myosin light chain and activation of myosin ATPase
Ca++
| this is different from the role Ca++ plays in generating tension in skeletal and cardiac muscle
191
in smooth muscle, _______ filaments and protein ______ form a cytoskeleton
intermediate, dense bodies
192
in smooth muscle, what attaches to the dense bodies of the muscle cell?
actin
193
in smooth muscle cells, each myosin molecule is surrounded by ______
actin filaments
194
how do T-tubules differ in smooth muscle?
-there are no T-tubules, but there are caveolae (small invaginations in the cell)
195
in smooth muscle, sarcoplasmic reticulum is more organized
true or false?
false, SR varies and is less organized
196
actin is more plentiful in which type of muscle?
muscle that is not striated (smooth muscle)
197
troponin is found in all types of muscle cells
true or false?
false, there is no troponin in smooth muscle
198
is there more or less myosin found in smooth muscle?
less myosin
- myosin filaments are longer
- entire surface of filament is covered with myosin heads
199
there is _____ cytoskeleton in smooth muscle
additional (intermediate filaments and dense bodies)
200
myosin pulls actin molecules in opposite directions to generate tension in which type of muscle cell?
smooth muscle
201
what is the biggest difference in the myosin of smooth muscle comapred to the myosin in other muscle?
myosin light chains: play a key role in regulating activity of myosin and its ability to bind with actin
202
smooth muscle contraction
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
smooth muscle relaxation
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
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
decrease, increase
205
changes in phosphatase activity alter ______ responses to Ca++
myosin's
206
smooth muscle contraction: store-operated Ca++ channels
- 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
smooth muscle contraction: membrane channels
- activated by depolarization or stretch
- causes an increase in intracellular Ca++
- leads to muscle contraction
208
smooth muscle contraction: membrane receptors
- 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
what are the 3 different channels (smooth muscle) that can be activated in sarcoplasmic Ca++ release
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
what are the 3 types of channels on smooth muscle that allow calcium entry into the cells
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
many ______ muscles are controlled by both sympathetic and parasympathetic neurons
smooth
212
hormones and paracrines can cause ______ muscle contraction
smooth
213
_____ constricts smooth muscle of airways (asthma)
histamine
214
_____ relaxes smooth muscle of blood vessels (male sexual response, exploited by viagra, cialis)
nitric oxide
215
smooth muscle contraction: electromechanical coupling
- contraction caused by electrical signaling or mechanical signaling
- contraction dependent on changes in membrane potential
216
smooth muscle contraction: pharmacomechanical coupling
- contraction caused by chemical signaling
| - no changes in membrane potnetial required
217
______ potentials fire actoin potnetials whent hey reach threshold (smooth muscle) (in the GI tract)
slow wave
218
_____ potentials always depolarize to threshold (smooth muscle) (in the GI tract)
pacemaker
219
_______ occurs when chemical signals change muscle tension through signal transduction pathways with little or no change in membrane potential
pharmacomechanical coupling
220
comapare the internal muscle structure of all three types of muscles
- skeletal: t-tubules and sarcoplasmic reticulum
- smooth muscle: no t-tubules; sarcoplasmic reticulum
- cardiac: t-tubules and sarcoplasmic reticulum
221
compare the structures that control movement of each type os muscles
- 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
compare the initiation of contraction of each muscle type
- skeletal: requires ACh from motor neuron
- smooth: stretch, chemical signals. can be autorhythmic
- cardiac: autorhythmic
223
poison
a substance that can cause illness or death when introduced into an organism
224
toxin
a substance produced in an organism that can cause illness or death when introduced into an organism
225
venom
toxin which is typically injected into an animal by another
226
which deadly substance is found in puffer fish? what organ does it affect?
- TTX
| - gonads, liver (by affecting voltage gated Na+ channels)
227
what was the role of TTX in the movie Serpent and the Rainbow?
-a witch doctor could create and maintain zombies using TTX and extract from Datura plant (contains hallucinogens like scopolamine and other alkaloids
228
curare in 1596
- "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
what are the medical uses for TTX?
- 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
what is curare? what does it do?
- 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
how do we use curare in modern medicine?
- 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
what is the active ingredient in pot? what is its role in plants?
- tetrahydrocannabinol (THC)
| - assumed to be a protective chemical in plants
233
is THC hydrophilic or hydrophobic?
THC is very lipid soluble, so very hydrophobic or lipophilic
| -this is what makes THC so available to your nervous system
234
the endocannabanoid system
- 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
explain the physiological process of the effects of THC on the nervous system
- 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
why is THC associated with the munchies?
-one of the specific effects of THC is to allow an increase in neuronal activity in hypothalamic areas that regulate appetite
237
how was the exploration of cannabanoids related to weight loss remedies?
- 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
what is botox
- 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
how does botox work?
- 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
cone snail toxin
- 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
explain the physiological process of cone snail toxin on the nervous system
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
what are some medical uses for cone snail toxin?
- 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
what is the main difference in TTX, botox, curare, and cone snail toxin?
-they all cause paralysis but by blocking different receptors
- TTX = Na+ receptors
- curare = ACh receptors
- botox= degrading proteins
- cone snail toxin = Ca++ receptors
244
endocrinology as a science
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
what did Ernest Starling deduct in regard to endocrinology and its relationship with pharmacology?
- endocrinology is the basis of pharmacology
| - cannot design drugs without understanding how natural substances work
246
more than one hormone can be produced in one endocrine gland
true or false
true
247
one hormone can only be secreted by one tissue
true or false?
false, more than one tissue secretes the same hormone
248
there is usually just one single target cell type for a single hormone
true or false?
false, more than one target cell type for a single hormone
249
a single target cell can be influenced by more than one hormone
true or false?
true
250
hormones are blood borne
true or false
true, but they are also neuronally derived (so false)
251
some hormones are excreted from tissues that have other _____
functions
252
chemical classification: structure, solubility, secretion, transport, and source of peptides
- structure: chains of amino acids (3-500+)
- solubility: hydrophilic
- secretion: exocytosis
- transport: free active peptide or precursor
- source: pituitary, pancreas, GI tract, etc
253
chemical classification: structure, solubility, secretion, transport, and source of amino acid derivatives
- 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
chemical classification: structure, solubility, secretion, transport, and source of steroids
- structure: cholesterol derivative
- solubility: hydrophobic
- secretion: diffusion
- transport: most bound to carrier proteins
- source: adrenal and sex steroids
255
_____ compounds are typically bound to carrier proteins to facilitate delivery
hydrophobic
256
______ compounds are not always bound to carrier proteins but they can be. Why?
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
hormone processing
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
what are the 7 post-translational modifications of peptide hormones
1) peptide cleavage
2) glycosylation
3) phosphorylation
4) sulfation
5) amidation
6) acetylation
7) subunit aggregation
259
examples of peptide cleavage
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
feedback control
this is predominantly negative, i.e. output counteracts input, and is frequently seen in the trophic hormones
-feedback can also be positive
261
thyroid stimulating hormone release from the anterior pituitary is an example of what type of feedback?
negative
262
neuroendocrine reflexes
combination of neural and hormonal processes, not the same as neuromodulation
-ex: knee jerk
263
neuromodulation
suite of neurons that regulate a variety of different behaviours
- sleep wake cycle
- arousal
- reward centers
264
hormone release: rhythyms
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
hormone delivery to the target site: carrier proteins
give examples of specific carreirs
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
how do carrier proteins help facilitate delivery of hormones to the target site?
- 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
which is faster, genomic or non-genomic responses?
genomic is much faster, these bind to nuclear receptors and cause transcriptional changes
268
hormone activation
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
the length of time for hormone half life follows the general pattern:
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
3 methods of hormone inactivation
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
endocrine dysfunction: hyposecretion
primary or secondary, usually result in atrophy of the endocrine gland and normally treated through replacement therapy
272
endocrine dysfunction: hypersecretion
primary or secondary, usually the result of a benign tumour (adenoma), normally treated through inhibition
273
what is atrophy?
when the gland has shrunk, not capable of producing sufficient amounts of the hormone
274
what is primary dysfunction? (endocrine dysfunction)
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
CRH is released from the _____
hypothalamus
276
ACTH is released from the _____
anterior pituitary
277
cortisol is released from the _______
adrenal cortex
278
what does the HPA axis stand for
hypothalamic pituitary adrenal complex
279
explain the HPA axis in simple terms
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
how would an injection of cortisol effect the HPA axis?
an injection of cortisol will inhibit release of CRH from the hypothalamus and ACTH from the anterior pituitary
281
endocrine dysfunction: target cell
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
what are the 3 main factors that contribute to endocrine dysfunction?
- hyposecretion
- hypersecretion
- target cell dysfunctions
283
response at target cell: up and down regulation
receptors at the target cell are themselves regulated in response to hormone levels influencing abundance and affinity
284
measurement of binding kinetics for hormone/receptor complexes relies heavily on ___?
the chemical law of mass action
285
according to the law of mass action, if Kd is high, binding affinity is ?
low
286
do all hormone receptor complexes adhere to the law of mass action?
- 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
response at target cell: permissiveness
one hormone cannot fully exert its effect without the other being present - dual action required
288
response at target cell: synergism:
the combined effect is greater than the sum of the parts
289
what does the combination of glucagon, epinephrine, and cortisol do to the glucose levels in the blood?
increase significantly (over 250 mg/dl)
290
what does the combination of glucagon and epinephrine do to the glucose levels in the blood?
slightly increases, not as much as the combination of glucagon, epinephrine, and cortisol
291
response at target cell: antagonism
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
membrane bound hormone receptors
- 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
nuclear hormone receptors
most lipophilic hormones act through nuclear receptors and many genes will have responsive elements
294
explain the process of carrier protein binding to a nuclear receptor
- 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
what is another name for posterior pituitary
neurohypophysis, pars nervosa
296
what is another name for anterior pituitary
adenohypophysis, pars distalis
297
as a foetus, how many parts do we have to the pituitary gland?
3
298
posterior pituitary
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
which hormones are released from the posterior pituitary?
oxytocin and vasopressin (predominantly but not always)
300
what are the abreviations for oxytocin and vasopressin?
oxytocin = OT and vasopressin = AVP
301
precursor peptides for OT and AVP (neurophysins) are produced int he _____
hypothalamus
302
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
neurohypophysis
303
reduced ECFV (extracellular fluid volume) increases plasma osmolarity which increases osmoreceptor activity which increases which hormone from the posterior pituitary?
vasopressin release
304
reduced ECFV (extracellular fluid volume) decreases left atrial volume which decreases arterial blood pressure which increases which hormone in the posterior pituitary?
vasopressin release
305
what two things can lead to an increase in vasopressin release from the posterior pituitary? What is the consequence of this?
increase osmoreceptor activity or decreased arterial blood flow
- increased H2O reabsorption in renal tubules
- vasoconstriction of vascular smooth muscle
306
vasopressin is an anti-diuretic hormone (reduction in urine flow rate or production)
true or false?
true
307
which two situations cause an increase in oxytocin release?
birth canal distension and infant suckling
308
birth canal distension causing an increase in oxytocin release is what kind of feedback loop?
positive - as the birth canal distends, more oxytocin is released until the baby is born
309
what is the effect of an increase in oxytocin release due to infant suckling?
increase in uterine muscle (myometrium) contraction during parturition, increase in milk ejection from breast
310
what are 3 behavioural aspects of oxytocin?
- 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
what are 3 behavioural aspects of vasopressin release?
- 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
hormones released from the anterior pituitary go through the ______
blood supply
313
what are the hormones that are released from the anterior pituitary
ACTH, TSH, FSH, LH, PRL, GH
314
adenohypophysial cells (anterior pituitary)
histological and cytological methods have provided definitive evidence on the cellular source for each hormone released from the adenohypophysis
315
which hormone from the anterior pituitary is a corticotroph
ACTH
316
which hormone from the anterior pituitary is a thyrotroph
TSH
317
which hormones from the anterior pituitary are gonadotrophs
FHS and LH
318
which hornome from the anterior pituitary is a lactotroph
PRL
319
which hormone from the anterior pituitary is a somatotroph
GH
320
hormones synthesized and released from the anterior pituitary are under the control of ______ hormones that can be stimulatory or inhibitory
hypophysiotrophic
321
name each hypophysiotropic hormone from the anterior pituitary and their associated pituitary hormone along with the final hormone produced
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
what does a release of TSH do to the body
-hypothalamic pituitary TSH axis
anterior pituitary releases TSH, stimulates the thyroid gland, releases T3 and T4, affects metabolic rate
323
what does the release of ACTH do to the body
-hypothalamic pituitary ACTH axis
anterior pituitary releases ACTH, stimulates adrenal cortex, release of cortisol, affects metabolic actions
324
what does the release of prolactin do to the body
dopamine stimulates release of prolactin from the anterior pituitary, stimulates mammary glands, breast growth and secretion
325
what does a release in growth hormone do to the body
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
what does the release of LH and FSH do to the body
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
we have TSH, ACTH, LH and FSH, prolactin, and GH. Which of these are under stimulating control? which are not?
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
structural characterisation of adenohypophysial hormones: GH family; growth hormone is well conserved, however there are many different variants of _____
prolactin
329
structural characterisation of adenohypophysial hormones: GH family; what are 3 different variations of prolactin
mammalian prolactin (normal), cleaved prolactin, spliced variant (deletion)
330
structural characterisation of adenohypophysial hormones: glycoprotein family
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
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?
alpha stays the same, beta varies
332
Pars intermedia
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
alphaMSH is derived from what? (what is the precursor?)
POMC
334
POMc is a precursor for which hormones?
ACTH, lipoprotein, beta endorphin
| -ACTH can split into alpha MSH (leads to melanin synthesis, immune response, decreased food intake)
335
which enxyme cleaves POMC to create the molecules that it serves as a precursor for?
proconvertase
336
normal growth means:
1) protein, fat, and cartilage synthesis
2) cell proliferation (hyperplasia and hypertrophy)
3) bone lenghtening (increased extracellular matrix)
337
normal growth is influenced by:
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
where do we find most of the calcium in our body?
in our bones
339
growth rate
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
____% of brain growth appears in the first two years of life
70
341
growth hormone (GH) production is stilumated by _____ and inhibited by ______
GHRH, GHIH (somatostatin)
342
GH is a ____ amino acid long polypeptide produced in somatotrophs
191
343
____ is the most abundant adenohypophysial hormone (4-10% of the wet weight of the gland approx 5-10mg)
GH
344
spontaneous secretion of GH over a 24 hour period usually peaks in the first ____ minutes of sleep
90
345
GH is transported in _____ attached to one or more _____ (even tho it's hydrophilic)
plasma, binding proteins
346
the somatomedin hypothesis
"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
where does the somatomedin hypothesis come from ?
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
insulin and IGF receptors
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
IGF's
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
what is a bone
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
the ______ is the mature bone shaft with the _____ at either end. In a growing bone the epiphysis is separated from the diaphysis by the ______
disphysis, epiphysis, epiphyseal plate
352
where does growth happen in a bone?
epiphyseal plate
353
bone growth (width)
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
bone growth (length)
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
the dual-effector theory
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
where does abnormal bone growth happen?
-can happen in a variety of regions where lesions occur (increase or decrease in growth hormone)
357
abnormal bone growth: lesion in anterior pituitary
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
abnormal bone growth: lesion in the liver
- 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
abnormal bone growth: lesion at the end organ
- 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
____ - involved in energy homeostasis. hypothyroidism = reduced growth, largely permissive
thyroid hormones (TH)
361
_____ - 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)
insulin
362
_____ 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)
androgens and estrogens
363
_____ - belongs to the GH family and influences mammary gland growth as well as aspects of the immune system
prolactin
364
______ - belongs to the GH family and influences neonatal development, metarnal glucose and amino acid supply. Peaks around mid pregnancy until full term
placental lactogen
365
____ - nerve growth factors (NGF's) - peripheral neurons, often used as therapeutic when people have neurodegenerative diseases such as alzheimer's
neurotropic factors
366
______ - red blood cell growth factor - released from kidneys, greater oxygen carrying capacity from more red blood cells
erythropoietin
367
______ - vascular injury repair but also involved in the development of artherosclerosis - how blood vessels mature
platelet derived growth factors
368
______ - enhances proliferation of epidermis, gut lining, pulmonary lining - epidermal growth factor released from cows saliva, promotes growth of plant
epidermal growth factors
369
_____ angiogenesis - fibroblast growth factors (growth of blood vessels) - transforming growth factors
tumour derived growth factors
370
what is the most tightly regulated ion in circulation?
Ca++
371
___% 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++
99, 0.9, 0.1
372
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
60
373
neuromuscular excitability - reduced calcium leads to _____ muscle contraction and high levels lead to _____ muscular contraction
tetanic, reduced
374
stimulus secretion coupling
many cells will require calcium to enter the cell to stimulate the secretion of a given substance
375
why regulate calcium? (5 reasons)
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
to maintain Ca++ balance, dietary intake should ___ Ca++ loss in the urine and feces
equal
377
bone is a living tissue that is packed with _____ crystals between a collagen matrix
hydroxyapatite
378
regulation of calcium always impacts phosphate concentrations
true or false?
true
379
what provides strength to bones?
Ca++ and phosphate hydroxyapatite crystals
-if we get crystallization of these at the wrong places it can cause things like kidney stones
380
bone remodelling
remodelling requires deposition and resorbtion
- osteocytes
- osteoblasts
- osteoclasts
381
osteocytes
mature bone cells
| -have Ca++ pumps on cell membrane
382
osteoblasts
bone builders responsible for depositing the collagen matrix
383
osteoclasts
bone breakers
- decrease the pH of the environment, crystlas are more likely to dissolve
- carbonic anhydrase drives the reaction
384
what are the 2 places we can get Ca++ from the bony matrix?
- 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
hormones involved in Ca++ regulation: parathyroid hormone
- 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
hormones involved in Ca++ regulation: vitamin D3
- cholecalciferol
| - needs to be converted to 1.25 - (OH) - vitamin D3 (calcitriol)
387
hormones involved in the regulation of Ca++: calcitonin
- the ONLY hypocalcaemic hormone
- decreases Ca++ levels in the body
- as Ca++ goes up, calcitonin goes up and vice versa
388
what is parathyroid hormones effect on bone
1) fast homeostatic regulation of Ca++ from bone fluid space
| 2) slower balancing of total body Ca++ from resorptive processes
389
partahyroid hormone (PTH) _____ calcium and ____ phosphate reabsorption in the kidneys
increases, decreases
390
parathyroid hormone (PTH)'s effect on intestines
actions are indirect through stimulation of vitamin D3 production
391
vitamin D
- 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
target site for vitamin D3
the gut is probably the best documented area of vitamin D3 action, where both fast and slow components are initiated
393
what is the concentration of Ca++ in the lumen
approx 1 mM
394
is the concentration of calcium higher in the lumen or in the cytosol
way higher in the lumen
395
____ and _____ are carrier proteins inside cells that Ca++ binds to to keep constant concentration
calbindin and calmodulin
-vitamin D initiates response, vitamin D defficiency can cause low [ ] of Ca++
396
ECaC
epithelial Ca++ channel = gate keeper of passive movement of Ca++ from outside to inside the cell
397
what are different modes of transport of Ca++ into our out of cells?
- 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
regulation of vitamin D with PTH: hypocalcaemic event
- 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
regulation of vitamin D with PTH: hypocalcaemic event
- 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
calcitonin
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
when plasma Ca++ concentrations go up, this stimulates the _____ gland ___ cells and causes an increase in _____ which lowers the plasma Ca++ concentration
thyroid, C, calcitonin
402
when plasma Ca++ concentrations go up, this stimulates the _____ gland ___ cells and causes an increase in _____ which lowers the plasma Ca++ concentration
thyroid, C, calcitonin
403
osteoblasts are derived from ____ in the bone marrow and osteoclasts are derived from ____ in the bone marrow
stromal cells, macrophages
404
osteoblasts are derived from ____ in the bone marrow and osteoclasts are derived from ____ in the bone marrow
stromal cells, macrophages
405
osteoblasts and its precursor cells produce two main messengers, what are they?
RANKL (receptor activator of NFkB ligand) and osteopritegerin
406
____ stimulates the production of osteoprotegerin
estradiol
407
why aren't men subject to high risk of osteoporosis like women?
- 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
thyroid hormones (T3 and T4)
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
thyroid hormones (T3 and T4)
tetraiodothyronine (T4) and triiodothyronine (T3) are both derived from thyroglogulin and synthesized in the follicular cells and the colloid of the thyroid gland
410
a lot of energy is required to synthesize T3 and T4, because oft his, tyrosines are subject to recycling
true or false?
true
411
what are 4 actions of thyroid hormones?
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
thyroid hormone abnormalities
- 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
hypothyroidism (3 different causes)
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
hyperthyroidism (3 causes)
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
possible symptoms of hypothyroidism
- 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
possible symptoms of hyperthyroidism
- 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
melatonin
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
what is the link between the pineal gland and the optic tract?
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
there is an inhibition of the pineal gland during _____
phosphotase (light)
420
reproduction follows cycles, so there is a link between _____, sex hormones, and reproduction
melatonin
421
the adrenal gland sits on top of which structure?
kidney
422
the adrenal gland has three layers to its cortex, what aret hese layers and which steroids do they each produce
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
adrenal hormones
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
cholesterol as a precursor for steroid synthesis
- 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
three main "parent" molecules of cholesterol
C21 - pregane (base of progesterone)
C19 - androstane (bases of androgens)
C18 - estrane (base of estrogens)
426
adrenocorticosteroids
1) gluticocorticoids: corticosteron - precursor for cortisol
| 2) mineralocorticoids - aldosterone (precursor is corticosterone)
427
sex steroids
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
mineralcorticoid
- 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
why are estrogens considered female sex steroids and androgens considered male sex steroids?
-in females, there's a higher concentration of estrogen and in males more androgens
430
dehydroepiandrosterone (DHEA)
- 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
adrenogenital syndrome
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
glucocorticoid release
- 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
what are the direct action of glucocorticoids
- 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
what are the permissive actions of glucocorticoids
-vascular collapse during stressful events in the absense of glucocorticoids
435
what are the anti-inflammatory and immunosuppresive actions of glucocorticoids
- 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
cortisol hypersecretion
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
cortisol hyposecretion
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
general adaptation to stress: primary alarm response
- catecholamine surge into the system
- increase in BMR
- increase in blood flow to required organs
- hepatic glycogenolysis
-mobilizing energy reserves immediately
439
general adaptation to stress: secondary resistance response
- described actions of cortisol on metabolism
- continued mobilization of glucose for central organs
- continued breakdown of alternative energy stores (lipids and proteins)
440
general adaptation to stress: tertiary exhaustion response
- 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
the adrenal medulla
-essentially acts as an extension of the sympathetic nervous system
442
catecholamine release from the adrenal medulla is largely under the control of the ____
SNS
443
both catecholamines are sotred in ____ granules
chromaffin
444
both catecholamines are the active ligands in the adrenergic system and they will bind to one of the 4 adrenergic receptors, what are they?
alpha 1 and 2, beta 1 and 2
445
physiological effect of epinephrine
- 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
adrenoceptors: alpha 1
- most sympathetic target cells
- ligand affinity is higher in norepinephrine than epinephrine
- 2nd messenger = PLC
- ex: generalized anterior vasoconstriction
447
adrenoceptors: alpha 2
- digestive system
- ligand affinity higher in norepinephrine than epinephrine
- 2nd messenger: decreased cAMP
- ex: decreased motility in digestive tract
448
adrenoceptors: beta 1
- heart and kidney
- ligand affinity is equal in epineprhine and norepinephrine
- 2nd messenger: increase in cAMP
- ex: inotropic and chronotropic actions
449
adrenoceptors: beta 2
- 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
adrenoceptors: beta 3
- adipose tissue
- ligand affinity is higher in norepinephrine than epinephrine
- 2nd messenger = increase in cAMP
- ex: mobilises lipids for subsequent catabolism
451
all adrenoreceptors are g-protein coupled receptors
true or false?
true
452
epinephrine reversal
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
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
hypothalamus, anterior pituitary, adrenal cortex
454
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).
sympathetic nervous system, epinephrine, arteriolar smooth muscle
455
islets of langerhans and pancreatic hormones
- 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
amylin
- released with insulin following a meal
| - slows down the appearance of glucose in blood
457
somatostatin
- 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
pancreatic polypeptide
- 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
explain the glucose activation of insulin secretion from pancreatic beta cells after an increase in extracellular glucose
- 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
fuel metabolism: fuel
carbohydrates, fats, proteins
461
fuel metabolism: metabolism
a generalist term for the chemical reactions that occur in the body
462
fuel metabolism: anabolism
the required energy input (ATP) and is the synthesis of larger macromolecules either for function or energy storage
463
fuel metabolism: catabolism
- breakdown of macromolecules
- ex: hydrolysisL glycogen broken down to glucose
- ex: oxidation: glucose broken down to ATP
464
the balance between anabolism and catabolism is not always straight forward. what are some exceptions?
- growth periods
- short and long term "gaps" in food intake
- absorptive (fed) and post-absorptive (fasted) states
465
what causes glucose levels to go up?
- glucose absorption from digestive tract
- hepatic glucose production
a) glycongenolysis
b) gluconeogenesis
466
what causes glucose levels to go down?
- transport of glucose into the cells
a) energy production
b) energy storage
- urinary excretion of glucose
467
proinsulin is made of what
C-peptide (connecting peptide) and insulin (A chain and B chain)
468
insulin - carbohydrates : facilitates glucose transport
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
in the absense of insulin, there are no ____ transporter in the membrane
GLUT-4
470
in the fed state, insulin signals the cell to insert ____ transporters into the membrane, allowing glucose to enter the cell
GLUT-4
471
in the fasted state, the hepatocyte makes glucose and transports itout into the blood, using ____ transporters
GLUT-2
472
in the fed state, the glucose concentration gradient ______ and glucose enters the hepatocyte
reverses
473
insulin - carbohydrates: inhibits glycogenolysis in the liver
- favoring carbohydrate storage
| - hypoglycemic hormone = job to ensure that there is sufficient energy stored in your system
474
insulin - carbohydrates: inhibits gluconeogenesis
-reduces circulating amino acids
475
insulins action on fat
- 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
insulins action on protein
- promotes amino acid uptake
- stimulates protein synthesis
- inhibits protein degradation
477
insulin as the ONLY hypoglycemic hormone
- 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
diabetes mellitus
-likely the most common endocrine disorder in the western world, literally means "honey running through"
479
type 1 insulin-dependent diabetes
lack of insulin secretion
| -normally seen in children and represents a small proportion of diabetics (normally genetically based)
480
type 2 or non-insulin-dependent diabetes
lack of insulin sensitivity
| -the most common form and invariably seen alongside obesity (80-90%)
481
insulin deficiency can cause what 6 things?
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
explain the process of an increase in hepatic glucose output due to insulin deficiency
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
explain the process of a decrease in glucose uptake by cells due to insulin deficiency
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
explain the process of a decrease in triglyceride synthesis or lipolysis due to an insulin deficiency
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
explain the process of a decrease in amino acid uptake by cells due to a deficiency of insulin
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
explain the process of an increase in protein degradation due to insulin deficiency
this can cause an increase in blood amino acids (and following symptoms) or muscle wasting which leads to weight loss
487
what is glucagon's relationship with blood glucose levels
there is a negative relationship b etween blood glucose levels and glucagon
488
what is glucagon's relationship with carbohydrates
carbohydrates stimulate hepatic glycogenolysis and gluconeogenesis (promoting the liberation of glucose into the circulation)
489
what is fats relationship with glucagon
- 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
what are proteins relationship with glucagon
-glucagon promotes hepatic protein catabolism (trying to liberate energy sources)
491
glucagon acts in the opposite way as insulin
true or false?
true
492
feasting and fasting actions of insulin and glucagon
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
