Physiology of the Adrenal Glands and Pancreas 114

1
Physiology of the Adrenal Glands and Pancreas 1/14

• Review of the autonomic nervous system (please
  review CH 15 on your own)
• What are the two faces of the adrenal gland?
  Cortex and Medulla
• What are the Hormones of Cortex?
• What are the Hormones of Medulla?
• What are some pharmacological applications?
• What is the function of the pancreas?
• What is are the two types of diabetes mellitus?

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Next Week we will have 5 pt pre-lab quizzes
EXAMPLE Lab 2 5 point pre-lab quiz- Choose the
best answer 1) True or False We will measure the
ventricular volume of the heart in todays
lab. 2) Which of the following is a preserved
heart we will study in todays laboratory
activity? a) Pig b) Cow c) Sheep d)
Dog e) Plastic model 3) True or False The
pig heart is quite different from the human heart
anatomically. 4) We will NOT identify arteries
and veins using which of the following? a)
Preserved Cat b) Cadaver c) Torso
model d) Microscope e) All the
above will be used 5) True or False The
structures of the electrical conduction system
are easily identified on the models, preserved
hearts and fresh hearts, any of which may be used
for the lab exam.
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What is the function of the autonomic nervous
system? (Please review the Autonomic Nervous
System CH 15)

• Two ANS branches the parasympathetic NS (PNS)
  used during relaxation and the sympathetic NS
  (SNS) used during stress
• Parasympathetic NS prepares body for functions
  that occur during the relaxed state (i.e. after a
  meal).
• Effects limited to cell at synaptic ending
• Acetylcholine (ACH) uses nicotinic then
  muscarinic receptors for ACH which is RAPIDLY
  destroyed at synapse
• Time of effect is very brief (msec)
• Sympathetic NS Prepares the body to FIGHT or Run
  Away!
• Two catecholamines epinephrine/norepinephrine
• released at a synapse NT or released into blood
  (endocrine)
• Catecholamines are destroyed much more slowly
  than ACH
• Why is time to effect longer? (msec, seconds,
  minutes or more) VIP SNS can also turn off
  the PNS!

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The adrenal glands are located superior to the
kidneys and help manage STRESS. The adrenal
gland has two parts an outer cortex makes
steroid-based hormones and an inner medulla makes
water soluble catecholamines (SNS). All these
endocrine hormones are delivered to body by the
blood stream!
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Why is it so important that the medulla be so
vascular in terms of the time needed to generate
a physiological response to EPI and NE? The
cortical regions take more time to produce their
steroids and secrete their hormones slightly less
rapidly. What would happen to your stress
response time if you had poor adrenal gland
circulation?
EPI/NE ?DHEA/Sex Steroids ?Glucocorticoids?Mineral
ocorticoids What hormones are produced in what
parts of adrenal gland?
6
The Fight or Flight response works because
exocytosis dumps Epinephrine and Norepinephrine
into the blood or into a synapse. What are the
structures of EPI and NE? How do drugs that look
like these catecholamines work?
7
NE and EPI specifically bind to adrenergic
receptors! How do you fine-tune adrenergic
effects in the body? Are all adrenergic receptors
alike?

• There are at least 5 different types of
  adrenergic receptor each receptor gives a
  different effect!
• Heart ?Force of Contraction Beta 1 ( adenylyl
  cyclase)
• Lung ?Bronchodilation Beta 2 ( adenylyl
  cyclase)
• Fat ?Energy release via Beta 3 ( adenylyl
  cyclase)
• Vasoconstriction/?Heart Rate Alpha 1
  (phospholipase C)
• Inhibition (IPSP?intracellular K) Alpha
  2(-adenylyl cyclase)
• Important Can you still name a function for each
  receptor subtype? (Good T.Q.)

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Why can a single hormone affect different cells
very differently? Why can the effect of a
hormone on a cell change over time?

• 1) What if a one heart cell has many alpha-1
  receptors and another has very few? Will all
  heart cells and people respond the same?
• 2) What if the cells of the lung begin to express
  fewer beta-2 receptors? Will your albuterol
  inhaler still prevent asthma?
• 3) How does each mechanism support a different
  part of fight or flight?
• 4) Why might it be useful to tailor a response
  (drug) so just one receptor type is activated?

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THE ADRENAL MEDULLA CONTAINS A LARGE NUMBER OF
CELLS THAT RELEASE EPI/NE INTO THE BLOOD (INSTEAD
OF A SYNAPSE) so the catecholamines are delivered
to the entire body!

• Sympathetic Nervous System has two ways to
  deliver info
• 1) Preganglionic axons innervate postganglionic
  cell that releases EPI/NE into a specific synapse
  on a specific target cell in a specific tissue.
• 2) Preganglionic axons innervate postganglionic
  cells of the adrenal medulla that store EPI/NE in
  vesicles. Exocytosis is used to secrete NE and
  EPI into interstitial fluids followed by
  diffusion through fenestrations to blood. Epi/Ne
  diffuses from blood through interstitium to
  target adrenergic receptors located on platelets,
  endothelial cells, or cells in tissues (i.e.
  heart)).
• THESE ARE TWO REDUNDANT DELIVERY METHODS!
• Why is redundancy important to cardiac function
  if you have a transplanted heart!
• Adrenergic receptors on target cells are very
  selective and only accept EPI or NE!

10
Many common drugs have their effect because they
look like (mimic) the catecholamines.

• Allergies Alpha-1 is used to dry up mucus
  membranes during stress, therefore you take
  phenylephrine as a decongestant!
• High Blood Pressure Alpha-1 increases heart rate
  and causes vasoconstriction.
• You may take the drug Prazosin to block the
  receptor so EPI/NE cannot activate PL-C.
• High Blood Pressure Beta-1 increases the force
  of contraction and can cause high blood pressure.
• The drug Atenolol fills the Beta-1 receptor so
  EPI/NE cannot activate adenyl-cyclase
• Asthma Beta-2 promotes promotes bronchodilation
• The drug Albuterol looks like EPI to
  preferenentially to Beta-2 receptors and turns
  Adenylyl cyclase on in only these cells
  (bronchodilation?you can breath again)
• CNS Inhibition Yohimbine prevents Alpha-2
  receptor activation, changing membrane potential
  of target cells. (Sex Begins Again)

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Because steroids are lipid-based it is difficult
to store them. As a result the cells of the
adrenal cortex produce and secrete their steroid
hormones when stimulated. Production takes time.
Therefore, the steroid response time is slower
than for catecholamines.
EPI/NE ?DHEA/Sex Steroids ?Glucocorticoids?Mineral
ocorticoids What hormones are produced in what
parts of adrenal gland?
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THE ADRENAL CORTEX SECRETES GLUCOCORTICOIDS,
MINERALOCORTICOIDS AND STEROIDS INTO THE BLOOD.

• The 3 Cortical Layers of adrenal cortex are
  distinguished by their secretions of
  cholesterol-based endocrine hormones
• 1) Inner-Zona Reticularis Anabolic and Sex
  Steroids
• Creates a pre-hormone called Dehydroepandrosterone
  (DHEA) for production of testosterone/estradiol
• Changes muscle development/personality
• Most testosterone/estradiol produced in gonads
• 2) Middle-Zona FascicularisGlucocorticoids-
  Cortisol
• Change carbohydrate metabolism blood glucose
• Catabolism of glycogen and protein
• Suppression of Immune system and Inflammation
• 3) Outer-Zona GlomerulosaMineralocorticoids-
  Aldosterone
• Change sodium reabsorption/ blood pressure

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The adrenal cortex handles stress primarily by
making cortisol , aldosterone, and DHEA which
becomes testosterone and its product estradiol.
Most DHEA is converted in the gonads.
DHEA
Prednisone and Dexamethasone are drugs that look
like cortisol and have anti-inflammatory effects
in the body just like cortisol.
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What are the stages of stress and adaptation to
stress? What is our health outcome if we are at
ant one stage?

• Stage 1 The Alarm Reaction
• Stage 2 The Stage of Resistance
• Stage 3 The Stage of Exhaustion
• How does this apply to you when a mugger jumps
  from around a corner?
• How does this apply to a soldier who has been in
  the field under fire for two months and come home
  on leave?
• How does this apply to a loved one who is finally
  succumbing to cancer?
• Why is it clinically important to consider the
  stage of stress that a person is experiencing?

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THE PANCREAS SERVES AS BOTH AN ENDOCRINE and an
EXOCRINE GLAND. IT RESPONDS TO THE GLUCOSE
NEEDS OF THE BODY AND ITS FEEDING STATUS.

• Exocrine secretions include digestive enzymes
  sent to duodenummore next week
• 3 Endocrine SecretionsInsulin Glucagon
  Somatostatin Islet of Langerhans Beta Cells
  Alpha Cells Delta cells
• Three Levels of Importance
• 1) Insulin Universal Well-Fed signalTyrosine
  Kinase Stimulates glucose uptake into cells as
  well as TG/glycogen/protein synthesisGROWTH
• 2) Glucagon Universal Starvation
  signalcAMP Stimulates Protein,TG and
  Glycogen breakdown
• 3) Somatostatin released following feeding and
  inhibits BOTH glucagon and insulin release?Feed
  Back!

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?Insulin ?Glucagon ?Somatostatin
?Digestive Enzymes and Bicarbonate
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Beta Cell Insulin production and release is
tightly regulated! Only a tiny part of the
original pro-hormone is used to make the active
hormone! The active hormone (insulin) is stored
in secretory vesicles until release (exocytosis)
is initiated by a calcium influx into the cell,
this permits insulin secretion out of the cell to
blood.
Disulfide bonds between two cysteines in peptide
sequence
ACTIVE HORMONE
Inactive Hormone or Zymogen
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Insulin creates its effect by stimulating a
Tyrosine Kinase.
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The two types of diabetes mellitus are
characterized by pathogenically high blood
glucose due different causes.

• Type I or Juvenile onset Characterized by a
  lack of (or insufficient) insulin secretion after
  a meal
• Type II or Adult Onset Characterized by the
  inability of cells in the body to response to
  insulin released from the pancreas. Insulin
  produced but does not function properly at target
  cells.
• These two diseases are very different and cause
  very different problems.