1QQ # 2Name on top edge, back side of paperAnswer on blank side of paper.
1. For the negative feedback loop for thermoregulationa) The hypothalmus is an afferent pathwayb) Somatic nerves are the efferent pathway to sweat
glandsc) Skeletal muscle tone would be increased as a
response to a drop in core body temperatured) Peripheral nerves are the afferent pathway that
convey skin temperature informatione) Cutaneous arterioles would dilate in response to a
drop in core body temperature.
Add coversor clothingor enter sleeping bag
Skin tempAnd Core body temp
Detected by thermoreceptors in skin
Activity in sensory nerves
Hypothalamus
Sympathetic nerves
Relax smooth muscle in cutaneous arterioles
Blood flow to skin
Heat loss by conduction & radiation
Somatic nerves
Muscle tone
Heat productionSweat Glands
Sweat production
Evaporative heat loss
Core temp.
Voluntary behaviorsRemove coversTurn on fan, etc via
Heat loss
Cerebral cortex
Conductive heat loss
Radiative heat lossConvective heat loss Central
thermoreceptors
Skeletal Muscles
Somatic nerves
Acclimatization & Feedforward
• Deviations from set point are minimized
• Learned (by experience)
• Anticipates changes of a physiological parameter
• Response begins before there is a change in the physiological variable
• Minimizes fluctuations
• Explain “chills” at onset of a fever
• Explain “sweat” when a fever “breaks”
• How does Tylenol reduce a fever?
To reach new,Higher set point
If setpoint is suddenly reset to a higher temperature, then actual temperature is LESS THAN the new set point, so one feels “cold” and adds clothing, curls up, and shivers. These are “Chills.”If setpoint is reset to a lower temperature or back to normal, then actual temperature is GREATER THAN the new lower set point, so one feels “hot” and removes clothing, fans, and sweats. These are “the sweats” when a fever breaks.
Central &PeripheralThermoreceptorsTylenol and other
non-steroidal anti-inflammatory drugs (NSAIDS) suppress the production of eicosanoids (IL-1, IL-6, etc) so effect of these on the set point in hypothalamus is minimized.
p. 579 Fig 16-18
Increasecell
metabolism
Increase Body Temp.
Failure of 1. Brain function &
2. Heat loss mechanisms
Sympathetic outflow
Blood Pressure
Blood Flow to brain
Disrupted functionof neurons
Cutaneous vasodilation
Heat Stroke
Sweating
Blood volume
Excessive SweatingMassive Cutaneous Vasodilation
Treating Heat Stroke
Positive feedback
• Inherently unstable• Examples of Positive Feedback in Physiology
– Heat stroke– formation of blood clot– menstrual cycling of female sex hormone
concentrations at ovulation– generation of action potentials in nerve fibers– uterine contractions during childbirth
• Each of these examples terminate naturally (self limiting)
Homeostasis is achieved by negative feedback loops: the integrator detects deviations from set point and orchestrates responses produced by effectors that return the parameter toward the set point.
Plasma Glucose Homeostasis
• Glucose metabolism
• Hormonal Control
• Disruptions of glucose homeostasis
• A Case Study
Homeostasis of Plasma Glucose Concentration
• Normal physiological range: 65-100 mg/dl• What is the set point?• Why is too much plasma glucose harmful?• Plasma glucose concentration = glucose entering the
plasma – glucose leaving the plasma• What are the mechanisms that regulate plasma
glucose concentration?• What are the components of the negative feedback
loop:– Glucose receptors?– Afferent pathway?– Integrator?– Efferent pathway(s)?– Effector organ(s)?
Phases:absorptive, post-absorptive, and fasting
Graph your daily caloric intake over a 48 hour period
6am 6am6pm 6pmNoon NoonMN MN
Cal
orie
sco
nsum
ed
6am Noon
PlasmaGlucose
?
?
Overlay absorptive and post-absorptive phases on the graph
Fig. 16.01
=sink
Abs
orpt
ive
Pha
se
Hepatic Portal System
Lipoprotein Lipase
Once inside, glucose is converted to something else, thereby maintaining a concentration gradientfor facilitated diffusion ofglucose into cells.
Islets of Langerhans
Alpha cells secrete glucagonBeta cells secrete insulinDelta cells secrete somatostatin
Route of blood
LiverTypical vasculature: Artery-Arteriole-Capillary-Venule-Vein-Heart
Hepatic portal systemArtery-Arteriole-Capillary-Portal Vessel- Capillary-Venule-Vein-Heart
Fig. 16.02
Post-absorptive phase
Glucose Sparing
Special case: Muscle wasting of starvation
Note: Nervous tissuecan use glucose and ketones
Special term:Glycogenolysis &Gluconeogenesis
Major Points• Absorptive phase lasts ~ 4 hours, cells “burn” glucose.• During absorptive phase, energy needs provided by
recently digested food• During absorptive phase, excess is converted to
stored fuel• During post-absorptive phase, energy need met by
release of stored fuels, most cells “burn” fatty acids, nervous tissue uses glucose and ketones.
• Fasting defined as greater than 12 hours after previous meal (some say 24 hrs)
• Fasting for several days has little effect on plasma glucose levels
The Issues
• How do cells “know” which fuel to “burn?”• How do cells “know” when to synthesize
glycogen or lipids and when to break down glycogen or lipid?
• What is responsible for the transitions from the absorptive and post-absorptive states?
• How does glucose get into “sink” cells?
Fig. 16.07Identify sensors, afferent pathway,integrator,efferent pathway,effectors
How is insulin secretion affected if plasma glucose is lower than set point?
Which cell types have insulin receptors?
Activates some enzymes, inactivates others:see next slide!
GLUT-4
Peptide hormone
Exercise (via an undescribed mechanism) increases the number of glucose transporters in muscle cell membrane
Diabetes mellitus:T1DM =beta cells fail to produce adequate insulin (5%)T2DM = target cells “resistant” (less responsive) to insulin
↑ plasma glucose →↑insulin secretion→↑glucose uptake into cells →↓ plasma glucose
Stimulatory actions of insulin in green
Inhibitory actions of insulin in dashed red
Absorptive Phase
Post-Absorptive Phase
?
The Integrator integrates multiple inputs
Glucose uptake, Storage, Lipogenesis
WHY? FF
FF
Thinking about foodFactors that influence Insulin Secretion
Another hormone that regulates plasma glucose concentration
Glucagon prevails during post-absorptive phase
Transition from absorptive to post-absorptive phase?
Graph your daily caloric intake over a 48 hour period
6am 6am6pm 6pmNoon NoonMN MN
Cal
orie
sco
nsum
ed
6am Noon
PlasmaGlucose
100
65
Overlay INSULIN SECRETION on the graph
Overlay GLUCAGON SECRETION on the graph
Glucose-counterregulatory controls
(oppose effects of insulin)
GlucagonEpinephrineCortisol (permissive effect)Growth hormone (permissive effect)
Fig. 16.10
EPI, yet another horomone inglucose homeostasis, effects opposite of Insulin
Don’t fret about receptors, afferent pathway, and integrator for this feedback loop.
Who Cares?
A Case Study• On our website at• http://webs.wofford.edu/davisgr/bio342/oggt.htm
A Case Study of Glucose Homeostasis A 35 year old male presented with the following complaints: frequent severe headaches upon awakening at 4:30 am, blurred vision, and fatigue due to excessive stress at work. The patient complained of routine 16 hr workdays followed by a midnight snack of breakfast cereal. An OGTT was ordered and provided the following results: During the second hour of the OGTT, the patient exhibited anxiety, paleness, hunger, tremulousness, and cold sweat. No additional tests were ordered. The patient was instructed to replace the midnight snack of cereal with a protein-rich snack.
Oral Glucose Tolerance Test
• Overnight fast, no beverages other than water
• Fasting blood sample• Ingest 75 grams glucose• Blood samples every 0.5
hours for 3-5 hours• Plot plasma glucose
concentration over time• Compare curves Sugar content
of Red Bull?
60
Stress,Emergency (fight or flight)
Effect onBeta cells
Effect on Alpha Cells
The Answer to the Problem?
• Rationale for substituting protein for carbohydrate midnight snack?
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