Week 4: Body energy homeostasis Flashcards
(92 cards)
1
Q
Give the overview of how humans maintain their body temperature within the optimal range.
A
Are endotherms - so able to generate own heat by metabolism
Can then stabilise core temperature by loss or gain of heat by exchange with the environment.
Are homeotherms - so remain at a relatively constant body temperature goal range
2
Q
How does heat production compare to heat dissipation in humans?
A
Equal
3
Q
How do humans generate their own heat? (endotherm)
A
Sum of all metabolic processes release heat (exothermic)
Increasing metabolic rate releases heat
Increasing activity = increases heat generation by ATP hydrolysis
Which in turn increases the rate of ATP production
4
Q
What are the two different differentiations of temperature in the human body?
A
Core temperature
Peripheral temperature
5
Q
What are the features of humans core body temperature?
A
Kept within tightly regulated limits (presever metabolism of brain, heart and organs)
Prioritised maintenance over peripheral temperature
Consists of major thoracic and abdominal organs and brain
2/3 of body heat content
6
Q
What are the features of humans peripheral core body temperature?
A
Peripheral temp can vary widely
Includes the skin, extremities of body (limbs) and subcutaneous tissue
1/3 of body heat content
Is less important in maintenance than core body temp
7
Q
What is the target range for core body temperature?
A
36.6 to 37.4 degrees
8
Q
What is the target range for peripheral body temperature?
A
30-32 degrees
9
Q
What mechanism allows there to be a difference between core and peripheral body temperature?
A
Vasoconstriction and/or vasodilation of blood vessels
10
Q
What factors contribute to heat production in a human?
A
Basal metabolic rate
Skeletal muscle activity
Metabolic factors
Thyroid disease
Medications
Convulsions
Fever
Environmental heat
Menopause
11
Q
What does basal metabolism contribute to heat production?
A
Is overall exothermic
Contributes 100kcal/hour - this would raise temperature by one degree per hour if there was no dissipation mechanism
12
Q
How does skeletal muscle activity contribute to heat production?
A
ATP hydrolysis releases heat
Can raise heat by 20 fold
13
Q
What are the different ways in which the CNS can influence body temperature?
A
Shivering thermogenesis
Non-shivering thermogenesis
Metabolic Control
Vasomotor control
Sweating control
14
Q
What are the different ways that heat can be carried from the core to the skin?
A
By blood (greater in vasodilation)
By fixed tissue conductance (this is minimal)
15
Q
What are the different ways that heat is lost from the skin to the ambient environment?
A
Evaporation _ by sweat
Radiation
Convection
Conduction
16
Q
What is conduction as a method of heat loss?
A
Transfer of heat by direct contact
Minimal in air by significant in water
17
Q
What is convection as a method of heat transfer?
A
Transfer of heat by air circulating the body
Varies with wind velocity
18
Q
What is radiation as a method of heat transfer?
A
Transfer of heat via electro-magnetic waves
Bidirectional - gain or loose heat
Can result in heat gain
19
Q
What is evaporation as a method of heat transfer?
A
Transfer of feat via conversion of liquid to gas
Evaporation of 1cc of sweat consumes 0.58kcal
Dominant mechanism of heat loss in hot environments
20
Q
What makes up the central thermoregulatory network?
A
Afferent neurons that realy info from the peripheral and core thermoreceptors
Thermal afferent pathway within the CNS
Thermoregulatory integration centre in the preoptic anterior hypothalamus
Efferent pathway providing autonomic and somatomotor inputs to effectors
Thermal effectors that control heat transfer to the environment and heat production in the body.
21
Q
What is the passive poikilothermic system in humans?
A
How the circulatory system and laws of physics determine heat transfer between the environment and core body temperature.
Is superimposed on by the central thermoregulatory network
22
Q
How might acclimatisation occur to a hot temperature?
A
Requires repeated exposure to same temperature
- increased sweat volume and decrease Na conc
- increased plasma volume and cardiac stoke volume
23
Q
How might acclimatisation occur to a cold temperature?
A
Requires repeated exposure to the same temperature
- increased body hair
- decreased sweat volume
- decreased plasma volume and cardiac stroke output
24
Q
What class of receptors is considered thermosensitive?
A
TRP channel members
Different receptors detect different temperatures from freezing cold (cold-pain) to burning hot (heat-pain)
25
What is the role of TRMP8 receptor?
Expressed on cutaneous afferent neurons are skin cold receptors - function demonstrated in dorsal root ganglia and trigeminal ganglia
Peak activation at 25 degrees, but ranges from 7 to 42 degrees.
Is known as the menthol receptor - stimulated by mint
26
What is the TRPV3 and TRPV4 receptor?
Found in keratinocytes when activates triggers paracrine signals that are responsible for skin warmth sensation and activate melanin production.
Activate from 30 to 50 degrees peak activation at 42 degrees.
27
What is the TRPM2 receptor?
Expressed in neurons in the pre-optic area of the hypothalamus act as central warm sensation neurons.
28
What receptors detects cold-pain?
TRPA1
29
What receptor detects heat-pain?
TRPV1 and TRVP2
also called the capsaicin receptor ( activated by capsaicin component in chilli)
30
What are the two different classes of thermosensory neurons found in the periphery?
What are there characteristic features?
1.Activated by innocuous warmth (34 to 42 degrees)
2.Activated by innocuous cold (14 to 30 degrees)
Both have cell bodies in the trigeminal ganglion (if innervating head and face) or cell bodies in the dorsal root ganglion for rest of body.
Are pseudounipolar - one axon projecting to skin or visceral, other to the ganglion
31
What are the different types of input for the thermoregulatory system?
Afferent sensory neurones that detect temperature in the periphery
Sensory neurons located within the brain that detect the temperature of the hypothalamus
32
What areas in the brain are associated with temperature discrimination?
Insula cortex
Somatosensory cortex
Ventral posterior thalamus
33
What parts of the brain are involved in temperature homeostasis?
POA - preoptic area of the hypothalamus
LPB - lateral parabrachial nucleus
Spinal Trigeminal Nucleus
34
What external factors can cause the body to increase in temperature?
Environmental thermal changes influence skin temperature, recognised by TRP channel family receptors and sends afferents to the POA
Infection triggers the immune response causes the release of pyrogenes which act on the POA
35
What internal factors influence body temperature?
Brain temperature
Spinal cord temperature
Visceral temperature
Detected by TRP channel family receptors and relayed to the POA by afferent neurons
36
What is the function of the POA in thermoregulation?
Integration of different afferent signals, central and peripheral.
To determine the most appropriate efferent signal in order to keep body temperature within the optimal range.
37
What are the different efferent signals that can be triggered by the POA to increase body temperature?
Sympathetic nervous system - BAT thermogenesis, cutaneous vasomotion, tachycardia (more blood to the skin)
Somatic - shivering thermogenesis
38
What is the response to cold to reduce convection?
1. Wearing clothes to trap a layer of air close to skin to reduce heat loss
2. Piloerection
39
What is the mechanism of piloerection?
Sympathetic stimulation of the alpha 1 adrenoreceptor triggers contraction of the arrector pili smooth muscle cells.
This causes the hair shaft to change from a shallow angle to something closer the 90 degrees
This traps air closer to the skin - reducing convection
Also causes slight elevations (goose bumps) on the skin
40
How do we reduce heat lost by radiation?
Cold environment is recognised by skin thermoreceptors.
Cold core body temperature and above are realyed to the anterior hypothalamus, specifically the POA.
This triggers sympathetic vasconstriction of cutaneous arterioles reducing blood flow to the skin.
This keeps hot blood away from the skin surface reduce lost by radiation, also cools the skin reducing sweating so less loss by evaporation
The cold also increases the affinity of adrenoreceptors.
41
What is apical skin?
Feature related to thermogenesis
Thick skin found in the palmar surface of the hand, the face and plantar surface of the foot. (extremities)
Has capillaries connecting the arteriole and venule
Also has a arteriovenous anastomosis (glomus body) which acts as shunt to move more blood between arteriole and venule as very low resistance pathway.
This has a high smooth muscle content under sympathetic control, allows greater control over heat lost by radiation
42
What is non-apical skin?
Feature related to thermogenesis
Skin that covers the majority of the body
Only has capillaries linking the arteriole and venule, these are under sympathetic control
43
How is the arteriovenous anastamosis (glomus body) control in order to regulate body temperature?
In cold environment - high basal sympathtic tone keep vasoconstricted reduce blood flow to the skin.
In hot environment - sympathetic tone decreases, vasodilation can occur, increase blood flow to the skin
This influence the rate at which heat is lost from the skin by convection
44
What are the different ways that vasomotor responses can be mediated to control body temperature?
Directly from the POA projecting into the Raphe Pallidus Nucleus and adjacent RVLM (rostral ventrolateral medulla)
Indirect pathway - from the VTA or the PAG (rostro-ventrolateral periaqueduct gray) to the RPA and the RVLM
45
What are the brain and peripheral regions involved in the efferent signals to cause vasoconstriction of blood vessels in the skin?
Direct or indirect pathways project onto the RPA and neighbouring RVLM in the brainstem.
Sends projections to the IML of the spinal cord
This regulates sympathetic outflow by sending projection to the sympathetic gandlion
The postganglionic fibre is a cutaneous vasoconstrictor neuron that acts on vascular smooth muscle.
46
What is the hunting reaction in the skin?
Blood vessels in the skin will oscilllate between cold induced vasodilation and vasoconstriction in order to prevent extensive damage to body tissue.
47
What is reactive hyperaemia?
Vasodilation in response to a period of ischemia - as seen in the Hunting reaction
48
What is the mechanism of the Hunting reaction?
Cold temperture detected - vasocontriction of cutaneous blood vessels in order to reduce blood flow to the skin, hence reducing heat loss.
Vasoconstriction causes ischemia in tissues, this causes anaerobic respiration.
The metabolites of anerobic respiration triggers upstream vasodilation to restore blood flow (this is reactive hyperaemia)
This allows the removal of anaerobic metabolites, once removed vasodilation quickly stops and vasoconstriction returns
49
What is raynauds syndrome/phenomenon?
An exaggerated response to the cold temperature or emotional stress
Present as pallor (constriction of blood flow), cyanosis (tissue hypoxia) or rubor (reperfusion)
50
What causes raynauds syndrome?
Preference for vasoconstriction over vasodilation
Increases reactivity of alpha 2 adrenorecptors in smooth muscle and increased endothelin-1 production from endothelial cells
Decreases vasodilatory peptides from sensory afferents and decrease NO release from endothelial cells.
Tendency for vasoconstriction response
51
Describe the progression of presentation of raynaud syndrome?
White digits - vasoconstriction - lack of blood flow to digits
Blue digits - cyanosis - partial vasoconstriction results in some return of blood flow, but low in oxygen
Red digits - vasodilation - return of blood flow.
52
What are the symptoms and causes of raynauds syndrome?
Sudden onset of cold digits and shpary demarcated colour changes
Can be primary or secondary to illness such as Lupus or systemic sclerosis
53
What is the treatment for raynauds syndrome?
Calcium channel blockers
Sildenafil (viagra ) vasodilatory drug
54
What are the obligatory methods of energy expenditure in a human?
All tissue: Standard metabolic rate - including sleeping and arousa themogenesis
All tissue: Diet induced thermogenesis
Skeletal muscle: Physical activity
55
What is the mediator of sleeping thermogenesis?
Thyroid
56
What is the mediator of arousal thermosgenesis?
Cortisol
57
What is the mediator of diet induced thermogenesis?
Insulin
58
What is the main mediator of physical activity in skeletal muscle?
Acetylcholine
59
What are the faculative (optional) components of energy expenditure in humans?
Skeletal muscle: regulated by Ach
- shicering thermogenesis
- voluntary active thermogenesis (exercise)
- non-excrsise activity thermogenesis (fidgeting)
Other tissue:
- non shivering thermogenesis
- diet induce thermogenesis
60
What regulates cold induced non-shivering thermogenesis?
Brown adipose tissue - SNS noradrenalin and thyroid
61
What regulates diet induced thermogenesis 2?
SNS noradrenaline (NOT insulin as in diet induced thermogenesis 1)
62
What is shivering thermogenesis?
Rapid and repeated skeletal muscle contraction at a frequency of 8-10 Hz.
increased body heat up to 5 fold
increase skeletal muscle tone
63
What is the mechanism behind shiviering thermogenesis?
Shaking possibly from increased activation of y motor neurons.
This triggers unstable activation of the muscle spindle reflex lead to rapid deactvation/activation cycle.
Cold receptors activated in the skin, activation of thermoregulatory cool afferent, relayed to POA in the brain. causes GABA release.
Perception of coolness in the neocortex also relays to the thalamus leading to activation of thermoregulatory cool afferent.
Disinhibited cold defense efferent relays to brain stem, which transfers the signal to spinal cord, which activates shivering by Ach releasing efferent from the ventral horn
**.
64
What is non-shivering thermogenesis?
Use of brown adipose tissue found surrounding the main arteries supplying the brain, heart and other major organs.
uses lipolysis to generate heat.
Mostly occurs in interscapular region where it is highly innervated by sympathetic nerves.
65
What is the mechanism of non-shivering thermogenesis?
Noradrenaline causes the breakdown of fatty acids in lipid droplets.
Release of fatty acids from brown adipose tissue causes uncoupling of the electron transport chain, by allowing H+ to leak through the UCPI receptor (rather than ATPsynthase) into the mitochondrial matrix (known as mitochondrial leak)
Short circuiting the elctron transport chain allos release of energy stored in H+ gradient as heat.
66
What is the neural mechansim behind non-shivering (BAT) thermogenesis?
Different regions in the brain detect cold temperature such as POA and PAG then send signal to RPA
Descending signals (premotor neurons) leave the brain from the PRA to the IML. Release glutamate or seratonin.
IML projects a preganglion fibre to the sympathetic gangline
That then sends a post-ganglioninc sympathetic output neuron to the brown adipose tissue, where it releases norepinephrine
67
How can skeletal muscle contribute to non-shivering thermogenesis?
Actions of SLN (sarcolipin)
Uncouples Ca2+ transport by the SERCA pump from ATPhydrolysis - allows ATP hydrolysis to occur without Ca2+ transport
Ca2+ independent ATP hydrolysis is dissipated as heat.
68
What are the different regions in the brain involved in non-shivering thermogenesis?
POA projects neurons directly onto the RPA and indirectly to the DMH which then signals to the RPA.
LH (hunger centre) signals directly to the RPA.
PAG signals directly to the RPA
RPA projects neuron out to the IML in the spinal cord
69
What can the POA trigger in response to low body temperature/cooling?
Vasoconstriction of cutaneous blood vessel to reduce blood flow to the skin
Descreased sweat command
Increased shivering and non Shiah Erin g thermogenesis and piloerection (indirectly by dorsalmedial hypothalamus)
70
What can the DMH (dorsomedial hypothalmus) trigger in response to cooling/low body temperature?
Shiver command
BAT thermogenesis command.
71
What are the behavioural changes associated with cooling/decreased body temperature?
Increases appetite
Increased physical activity
Curled up body position
72
What hormones control basal metabolic rate?
Thyroid hormones - can increase and decrease basal metabolic rate in response to temperature changes.
73
Describe how pre-cursors for T3 and T4 are produced in the thyroid gland?
1. TSH increases Na+/I- symport on the basolateral membrane of follicular cell - causes iodide trapping
2. Iodide is transported into lumen by pendrin transporter
3. TSH binds to TSH-R stimulates Thyroglobin production in the follicular cell ER and secreted into the lumen
4. apical membrane bound DUOX2 produces H2O2.
5. Iodide is oxidise by thyroid peroxidase (TPO) to iodine (H2O2 acts as electron acceptor)
6. TPO catalysed iodination of thyroglobin in the follicular lumen, forming MIT or DIT
74
Describe how thyroid hormone pre-cursors are converted to T3 and T4?
Undergo coupling
Two DIT molecules combine to form T4
One MIT and one DIT molecule combine to form T3
This process is known as conjugation
75
How are thyroid hormones secreted from the thyroid? Detailed mechanism
TSH triggers endocytosis of iodinated thyrogobin into the follicular cell cytoplasm.
Undergo proteolysis (break peptide bond) to form T3 and T4
TSH stimulates secretion of T4 and T3 into circulation by facilitated diffusion.
Finally TSH stimulates growth factor effect causing hyperplasia within the thyroid gland
76
What is the importance of the Hypothalamus- pituitary Thyroid axis in regulating body temperature?
Exposure to cold
Receptors in hypothalamus detect change
Trigger secretion of TRH
Triggers the anterior pituitary gland to secrete TSH
Stimulates the thyroid gland to produce T3 and T4, secrete into blood and grow and develop
Elevated T3 increases basal metabolic rate
Increased levels of T3 and T4 how a negative feedback effect on the hypothalamus and thyroid gland.
77
What are the effects of thyroid hormone on the target cell?
T3 and T4 are mainly carried in the plasma in association with thyroxine binding globing (TBG).
When T3 or T4 reach the cell membrane can diffuse directly across (if free) or are transported by carrier proteins (MCT8)
Once in the cell, most T4 is converted to T3 by deiodinase enzyme which removes the iodine.
Binds to nuclear receptors thyroid hormone receptor.
The activated receptor forms a heterodimer with retinoid X receptor then binds to the thyroid response element on DNA.
This alters gene expression/conversion to mRNA.
78
How can the effect of thyroid hormones be inactivated once in the cell?
5'/3' deiodinase activity is restricited by low calorie intake - low basal metabolic rate in starvation.
Deiodinase can also inactivate T4 to reverse T3 by removing a different iodine (closest to the carboxyl group).
79
What are some of the genes that thyroid hormones can control?
Na-K pump
Gluconeogenic enzymes
Respiratory enzymes
Myosin heavy chain
Beta-adrenergic receptors
Many more
80
How are thyroid hormones able to increase body temperature?
Increase basal metabolic rate by triggering futile cycles, as cycles are futile they have no tangible effect so can continue until plentiful heat is generated.
81
Give examples of the futile cycles that thyroid hormones are able to stimulate.
Na+/K+ ATPase activity and Na+ leak back into the cell cytoplasm
Lipogenesis and lipolysis
Protein synthesis and proteolysis
All three of these cycles generate heat.
82
What is the effect of thyroid hormones in brown adipose tissue?
Increase expression of UCP1 in brown adipose tissue - increases heat generation as more uncoupling of H+ transport with ATPsynthase.
83
What is the effeect of thyroid hormone in the heart, skeletal muscle and adipose tissue?
Increased expression of beta adrenoreceptors
Increased sensitivity to catecholamines (adrenaline)
Increased liberation of metabolites and increased supply of these and O2 to tissues to sustain faster metabolic rate.
84
What is the response to heat in non-apical skin?
Heat detected by POA, PAG and VTA which really signals to the RPA and neighbouring RVLM.
Project neurons to the IML in the spinal cord
Projects sympathetic efferent to the sympathetic ganglion
Post-ganglionic neuron acts sweat gland, ACh releases causes sweating.
Sweat gland releases Bradykinin which acts on vascular smooth muscle as a vasodilator.
This causes heat loss by evaporation and radiation.
85
Give an overview of apocrine sweat glands?
Few in number and large in diameter
Ducts empty into hair follicles
No role in temperature regulation in humans, may act as a source of pheromones
86
Give an overview of the role of eccrine sweat glands.
Numerous and small in diameter
Essential role in temperature regulation
Ach released from sympathetic neruones causes sweating through a Ca2+ dependent stimulation of Cl- secretion from coil cells
87
What is the mechanism of sweat secretion from eccrine glands?
NKCC transporter on the basolateral membrane - influx of K+, Na+ and Cl- in the cytoplasm
Na+ K+ ATPase increases K+ content further
K+ leaks out of basolateral membrane
Cl- moves out the apical membrane into the lumen by ion channels.
This encourages the move of Na+ into the lumen down an electrochemical gradient, water follows forming sweat secretions
Some of sweat secretions may be reabosbred through ENaC and CFTR in the duct cells closer to the surface.
88
What is the neural circuit underpinning sweating in the body?
POA detects rise in temperature
Projects to the RVMM
Porjects pre-motor neurons to the spinal cord IML
IML projects preganglion neurons to the sympathetic ganglion
Post ganglioninc fibres (sympathetic output neuron) projects to the sweat gland and releases Ach to trigger sweating.
89
Describe the mechanism underpinning fever?
Immune response to foreign substance - often a pathogen.
Activated innate immune cells release cytokines can trigger an acute phase response including fever production.
Cytokines such as IL-1beta act as endogenous pyrogens in a signalling cascade, that causes peripheral organs (mainly the liver) and the centrL CNS to produce PGE2
PGE2 inhibits warmth-sensitive neurons and activates thermal effectors (vasomotor), heat retention and heat production (shivering, non shivering) .
Results in a raised core body temperature.
Think of as regulated hyerpthermia
90
What is the acute phase response in fever?
Cytokines produced in the immune response stimulate endothelial cells in the OVLT area of the brain - cause to release PGE2
PGE2 acts on the hypothalamus - brings about changes related to fever.
91
How does menopause cause hot flushes?
Decreased ostrogen levels results in increased Nueokinin B production in KNDy neurons in the arcuate nucleus.
This binds to NK3 receptors on the medial Pre-optic nucleus.
This activates an efferent neural pathway that increases heat defence effectors and heat production methods.
92
What medication can be used to reduce hot flushes in menapause?
NK3Receptors antagonists
