1QQ # 2

1. 1QQ # 2 Name on top edge, back side of paper Answer on blank side of paper. • For the negative feedback loop for thermoregulation • The hypothalmus is an afferent pathway • Somatic nerves are the efferent pathway to sweat glands • Skeletal muscle tone would be increased as a response to a drop in core body temperature • Peripheral nerves are the afferent pathway that convey skin temperature information • Cutaneous arterioles would dilate in response to a drop in core body temperature.

2. Convective heat loss Conductive heat loss Skin temp Radiative heat loss Detected by thermoreceptors in skin Hypothalamus Heat loss Sympathetic nerves Sweat Glands Muscle tone Heat production Relax smooth muscle in cutaneous arterioles Activity in sensory nerves Blood flow to skin Sweat production Evaporative heat loss And Core body temp Heat loss by conduction & radiation Core temp. Add coversor clothingor enter sleeping bag Central thermoreceptors Cerebral cortex Somatic nerves Voluntary behaviors Remove coversTurn on fan, etc via Somatic nerves Skeletal Muscles

3. 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

4. Central &PeripheralThermoreceptors p. 579 Fig 16-18 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.” • Explain “chills” at onset of a fever • Explain “sweat” when a fever “breaks” • How does Tylenol reduce a fever? Tylenol 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. 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. To reach new, Higher set point

5. Blood Pressure Blood Flow to brain Cutaneous vasodilation Disrupted functionof neurons Sympathetic outflow Sweating Heat Stroke Massive Cutaneous Vasodilation Excessive Sweating Blood volume Treating Heat Stroke

6. 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.

7. Plasma Glucose Homeostasis • Glucose metabolism • Hormonal Control • Disruptions of glucose homeostasis • A Case Study

8. 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

9. Graph your daily caloric intake over a 48 hour period PlasmaGlucose ? ? Calories consumed 6am Noon 6am 6am Noon MN Noon MN 6pm 6pm Overlay absorptive and post-absorptive phases on the graph

10. =sink Fig. 16.01 Lipoprotein Lipase Absorptive Phase Hepatic Portal System Once inside, glucose is converted to something else, thereby maintaining a concentration gradientfor facilitated diffusion ofglucose into cells.

11. Islets of Langerhans Typical vasculature: Artery-Arteriole-Capillary-Venule-Vein-Heart Liver Alpha cells secrete glucagon Beta cells secrete insulin Delta cells secrete somatostatin Hepatic portal system Route of blood Artery-Arteriole-Capillary-Portal Vessel- Capillary-Venule-Vein-Heart

12. Fig. 16.02 Special case: Muscle wasting of starvation Glucose Sparing Special term: Glycogenolysis &Gluconeogenesis Post-absorptive phase Note: Nervous tissuecan use glucose and ketones

13. 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

14. 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?

15. Fig. 16.07 Identify 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?

16. Activates some enzymes, inactivates others:see next slide! Exercise (via an undescribed mechanism) increases the number of glucose transporters in muscle cell membrane Peptide hormone GLUT-4 ↑ plasma glucose →↑insulin secretion→↑glucose uptake into cells →↓ plasma glucose Diabetes mellitus: T1DM =beta cells fail to produce adequate insulin (5%) T2DM = target cells “resistant” (less responsive) to insulin

17. Stimulatory actions of insulin in green Inhibitory actions of insulin in dashed red

18. Absorptive Phase Post-Absorptive Phase

19. ? Thinking about food Factors that influence Insulin Secretion FF FF WHY? Glucose uptake, Storage, Lipogenesis The Integrator integrates multiple inputs

20. Another hormone that regulates plasma glucose concentration Glucagon prevails during post-absorptive phase Transition from absorptive to post-absorptive phase?

21. Graph your daily caloric intake over a 48 hour period PlasmaGlucose 100 65 Calories consumed 6am Noon 6am 6am Noon MN Noon MN 6pm 6pm Overlay INSULIN SECRETION on the graph Overlay GLUCAGON SECRETION on the graph

22. Glucose-counterregulatory controls (oppose effects of insulin) Glucagon Epinephrine Cortisol (permissive effect) Growth hormone (permissive effect)

23. Fig. 16.10 Don’t fret about receptors, afferent pathway, and integrator for this feedback loop. EPI, yet another horomone inglucose homeostasis, effects opposite of Insulin

24. Who Cares?

25. 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.

26. 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?

27. 60 Hypoglycemia

28. Stress,Emergency (fight or flight) Effect on Alpha Cells Effect on Beta cells

29. The Answer to the Problem? • Rationale for substituting protein for carbohydrate midnight snack?