Transcript Physiology of the Adrenal Glands and Pancreas 1/18

Physiology of the Adrenal Glands
and Pancreas 1/11 and 1/13
• Review of the autonomic nervous system (please
review CH 15 on your own)
• We are starting with CH 17, please give it a skim to look at its content
prior to lecture. Lecture tests will cover what is in notes, the textbook
will help you better understand lecture content.
• What are the faces of the adrenal gland?
– Adrenal Cortex-outer and Adrenal Medulla-middle
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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?
Mondays we will have a 5 pt pre-lab quiz for each lab activity. EXAMPLE
for Endocrine Lab (we will not have a pre-lab quiz for lab#1 this week)
Sample Pre-Lab Quiz shown below:
Lab 1 Endocrine System: 5 point pre-lab quiz- Choose the best answer
1) True or False: You will be asked to draw organs and tissues in lab.
2) Which of the following will be used in this lab?
a) Pig pancreas b) Cow adrenal gland c) Sheep ovary e) None of above
3) True or False: Human blood glucose concentration is a function of the
hormone insulin, and blood glucose will be examined using a finger prick
and a hand-held glucose meter.
4) Which will not be directly examined in lab with a microscope?
a)_Adrenal medulla b) Thyroid follicle c) Heart d) Ovarian follicle
5) True or False: In lab we will collect saliva samples to evaluate plasma
cortisol, epinephrine and norepinephrine concentrations.
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!
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!
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Mineralocorticoids
What hormones are produced in what parts of adrenal gland?
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?
NE and EPI specifically bind to adrenergic receptors! How do you finetune 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.)
Why can a single hormone affect different cells very differently?
Why can the effect of a single hormone on a cell change over time?
1) What if one heart cell has many alpha-1 receptors and another has
very few? Will both heart cells, differrent cells, and people
respond the same? So….Why do drug dosages vary????
2) What if the cells of the lung begin to express fewer beta-2
receptors? Will your albuterol inhaler still prevent asthma if used
every day for two weeks?
3) How does each adrenergic receptor sub-type support a different
part of fight or flight in different organs?
4) Why might it be useful to “tailor” a response (drug) so just one
receptor type is activated?
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!
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 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)
Because steroids are lipid-based it is difficult to store them. As a result
the cells of the adrenal cortex synthesize and secrete their steroid
hormones only when stimulated. Production takes time. Therefore, the
steroid response time is slower than for catecholamines.
EPI/NE DHEA/Sex Steroids GlucocorticoidsMineralocorticoids
What hormones are produced in what parts of adrenal gland?
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 Fascicularis:Glucocorticoids- Cortisol
– Change carbohydrate metabolism= +blood glucose
– Catabolism of glycogen and protein
– Suppression of Immune system and Inflammation
• 3) Outer-Zona Glomerulosa:Mineralocorticoids- Aldosterone
– Change sodium reabsorption/ +blood pressure
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 just
like the hormone cortisol.
Cortisone is a drug (cream or shot)
that looks like cortisol (insect bites?)
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 comes 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?
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
duodenum…more next week
• 3 Endocrine Secretions: Insulin Glucagon
Somatostatin
Islet of Langerhans: Beta Cells Alpha Cells Delta cells
• Three Levels of Importance:
• #1) Insulin: Universal Well-Fed signal>>Tyrosine Kinase
Stimulates glucose uptake into cells as well as
TG/glycogen/protein synthesis>>GROWTH
• #2) Glucagon: Universal Starvation signal>>++cAMP
Stimulates Protein,TG and Glycogen breakdown
• #3) Somatostatin: released following feeding and inhibits
BOTH glucagon and insulin releaseFeed Back!
Insulin
Glucagon
Somatostatin
Digestive
Enzymes and
Bicarbonate
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
Insulin creates its effect by stimulating a Tyrosine Kinase.
There are three types of diabetes mellitus that are all
characterized by pathogenically high blood glucose.
Diabetes is the epidemic of our generation! MN and WI counties,
within 25 miles of Winona State University based on 2008 Census data and
the national Type 2 Diabetes estimate of 8.3% affliction. (CDC 2010).
Winona Houston Fillmore Wabasha Buffalo Trempeleau TOTAL
County
13,425 27,754
Population 49,879 19,244 20,838 21,884
153,024
• Type I or Juvenile onset: Characterized by a lack of (or
insufficient) insulin secretion after a meal (no beta cells)
• 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,
eventually results in failure of beta-cells and insulin
dependence
• Gestational Diabetes: Characterized by a transitory insulin
resistance during pregnancy. Aberration of an intent by mom’s
endocrine system so save nutrients for the fetus (poorly understood etiology)
• These three diseases are very different and cause very
different problems.
Current criteria for the diagnosis of diabetes
ADA 2011 Standard of Care, Diabetes Care, 2011:34, S4-S10
Any One of Following Defines Person as Being Clinically Diabetic
• Hemoglobin A1c Glycosylation Value: A1C 6.5%- measures long-term
glycemic control.
• Fasting plasma glucose (FPG) of 126 mg/dl (7.0 mmol/l) or more with
no caloric intake for at least 8 hours
• 2-hour plasma glucose of 200 mg/dl (11.1 mmol/l) or more during an
oral glucose tolerance test (OGTT) with load of 75 glucose in water
• Classic symptoms of hyperglycemia or hyperglycemic crisis, and
random plasma glucose of 200 mg/dl (11.1 mmol/l) or more
• In the absence of unequivocal hyperglycemia, result should be confirmed
by repeat testing.
• Testing for diabetes in asymptomatic (means one need not be aware of
having disease symptoms-potentially silent)