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?