1. The Endocrine System

2. Fig 16.1 Hormones are like… Goal is NOT to control…
Goal is to control…

3. Hs are “receptor specific”

4. Magnitude of response is affected by:1) 2)

5. Up Regulation & Down Regulation

6. Controlling the Release of Hormones
Fig 16.4
also:
Post. Pit.
e.g.
Na+, K+, glucose

7. Hypothalamic Control of the Pituitary Gland
Fig 16.5

8. Hypothalamic Control of the Pituitary Gland
Fig 16.5

9. Fig 16.1 Hormones are like… Goal is NOT to control…
Goal is to control…

10. Control of ECF Osmolality (and volume) by ADH

11. Control of ECF Osmolality (and volume) by ADH
“Osmolality” is concentration based on # of solutes per Kg of water.
normal range = mOsm
Clinical application:
Most lab results on blood do not show osmolality
Na+ is responsible for vast majority of osmolality
Osmolality = 2X sodium conc
E.g.:
Na+ = 135 mEq/L
Na+ = 145 mEq/L
Na+ = 155 mEq/L
Which pt is dehydrated?
ADH is usually released in response to  osmolality but also in response to:
Pain
 BP
Drugs such as nicotine, morphine, barbiturates

12. ADH and Diabetes Fig 16.1 Not diabetes mellitus
But a rare form… diabetes insipidus
Insufficient ADH results in…
1) Excessive diuresis
2) Dehydration
3) Thirst
May be due to…
Tumor of pituitary g.
Head trauma
Radiation damage
Kidneys that don’t respond to ADH
Infection

13. ADH and Alcohol Fig 16.1 Alcohol inhibits release of ADH
So diuresis would …
It’s ironic…
You’re drinking liquids but …
“You pee out more than you drink in”
Results in dehydration

14. ADH
Fig 16.1
Source?
Target?
Effect(s)?
Variable(s) regulated?

15. Control of metabolism by TH (Thyroid H. a.k.a. Thyroxine)
Metabolism is…
Is actually 2 Hs…T3 and T4
Most of T4 is converted to T3 at target tissues.
Source…
Target tissues:
most body cells
except brain, spleen, testes, and uterus
Effects (2)
 basal metabolism (your “idle speed”) which …
Burns Calories
Produces heat
Body temp rises
 # of adrenergic receptors on blood vessels thereby… ________ BP
Fig 16.9

16. Thyroid Disorders Fig 16.10 Grave’s disease = hyperthyroidism
Goiter = hypothyroidism,  TH (thyroxine)
Due to insufficient iodine - an “essential” micronutrient found in…
Iodine is an essential component of TH
Grave’s disease = hyperthyroidism
An autoimmune disorder
antibodies mimic TSH thereby  release of TH (too much)
S&S= metabolism, weight loss,  temp, sweating,  and irregular HR
Possibly exopthalmos
Trtmt= remove portion of thyroid gland by surgery or destroy with radioactive iodine
Colloid precursors accumulate
thus enlargement of gland
Prevention = iodized salt
Trtmt: Synthroid = synthetic TH
TSH – high or low???

17. TH
Fig 16.1
Source?
Target?
Effect(s)?
Variable(s) regulated?

18. Regulation of ECF Ca++ by PTH
Fig 16.12
ECF concentration of Ca++ critical for…
Nerve impulses
Muscle contraction
RMPs
Blood clotting
Bones
Source = parathyroid glands
Targets and effects (3)… 1) 2) 3)
But what if ECF [Ca++] is already too high?
Back off on release of PTH

19. PTH
Fig 16.1
Source?
Target(s)?
Effect(s)?
Variable(s) regulated?

20. Q & A

21. Q & A

22. Q & A

23. Q & A

24. Q&A

25. Blood Glucose Glucose is…
A “simple” carbohydrate. C-C-C-C-C-C a.k.a. “blood sugar.”
Used as a fuel by virtually all body cells to produce _______
Enters muscle and fat cells by facilitated diffusion…
These cells absorb glucose too slowly on their own.
Insulin causes vesicles to implant GLUT4 proteins into cell membrane
rate of G absorption  10X-20X
Exceptions: brain & liver. – do not need insulin to absorb G. (Insulin does encourage liver to convert G to glycogen. Therefore, liver does absorb more G in presence of Insulin but not by transporting it.)
Video;
How insulin works
Muscle/fat cells

26. Set point = 90 mg/dl Normal range (fasting) = 70 – (100-120) mg/dl
Blood Glucose Values
Normal range (fasting) =
70 – ( ) mg/dl
(a.k.a. mg/100ml)
Set point = 90 mg/dl
> 140 mg/dl = hyperglycemia
< 60 mg/dl = hypoglycemia

27. Why be concerned about Hyperglycemia?
Stimulates fat cells to store glucose as fat.
Stimulates appetite
Thus perpetuates obesity epidemic
At values >300 mg/dl
 diuresis (polyuria), dehydration, polydipsia, and polyphagia
**the most common S&S of DM
Proteins are damaged by glycation (glucose binding) resulting in
e.g. Cataracts, retinopathy = #1 cause of blindness in U.S.
e.g. neuropathy – poor sensation …
e.g. arteriosclerosis = poor circulation and slow-to-heal wounds, gangrene, amputations
Ketoacidosis if…
Diabetic coma
Death

29. Effects of Chronic Hyperglycemia

30. Why is diabetes (and hyperglycemia) so common?

31. Why be concerned about Hypoglycemia?
S&S?
Initially: light-headed, LOC, syncope, nausea, sweating, headache, hand tremors, cool pale skin
Later: combativeness, convulsions, unconsciousness
Common cause: misuse of insulin
Some people experience “rebound” hypoglycemia…

33. Side by Side Comparison

34. Control of Blood Glucose
Fig 16.19

35. Diabetes Mellitus (DM)
1 out of every 3 Americans has DM or pre- DM, 105,000,000 people
7th leading cause of death in USA
$280,000,000,000 spent (wasted) annually
Diabetes =
Mellitus =
Two Flavors =
Type 1 (always IDDM)
Type 2 (usually NIDDM but may become IDDM)

36. Diabetes Mellitus – Type 1
Less common - 10% of DM cases
Formerly called “juvenile onset” and IDDM
Usually appears before age 15.
Pancreatic beta cells do not produce insulin. They’ve been destroyed.
Cause: autoimmune destruction of pancreatic cells
Viral (enteroviruses) infection triggers the destruction
Viral markers are so similar to markers on pancreatic cells that antibodies destroy both
Destruction is gradual (months or years)
No insulin produced/released therefore… hyperglycemia…
- When [G] > 300 mg/dl
- Polyuria…
- Polydipsia…
- Polyphagia…

37. Diabetes Mellitus – Type 1 (cont’d)
Possibly results in DKA…
Probable lipidemia & high cholesterol which  risk of …
Atherosclerosis  stroke, heart attack, blindness, kidney failure,
There is a genetic predisposition but…
Trtmt: daily injections of insulin for life
Is therefore IDDM
Injections coordinated with meals and activities
Implantable insulin pumps
Pancreatic beta cell transplants (33% success)

38. Q&A – DM, Type 1

39. Diabetes Mellitus – Type 2
More common - 90% of cases of DM
Formerly called “adult onset” and NIDDM
Pancreatic beta cells do produce insulin but …
# of insulin receptors on muscle and fat (and liver?) is reduced OR…
Receptors have become “insulin resistant”
Either way… rate of glucose uptake into cells is slowed resulting in…
- hyperglycemia
Causes:
Sugary diet and lack of exercise
Carrying too much body fat
Fat cells produce hormone-like compounds (adipokines) that make target cell receptors resistant to insulin
90% of all cases occur in overweight adults and overweight children
Genetics
Results :
hyperglycemia… polyuria… polydipsia… polyphagia…
Possible DKA…
Probable lipidemia & high cholesterol which  risk of …
- Atherosclerosis  stroke, heart attack, blindness, kidney failure

40. Diabetes Mellitus – Type 2 (cont’d)
The DM Type 2 epidemic
In % of adults in North America
By % “ “ “ “
More & more cases ( incidence), and more cases in young children…. …no longer “adult onset.”
Trtmt:
Most cases prevented/controlled by smart food choices and exercise
Meds such as Glucophage, Amaryl, Metformin
Monitor blood sugar with Hb A1c (Glycosylated Hemoglobin)
Possible insulin injections (but still not considered “Type 1”)
-- so IDDM no longer distinguishes Type 1 from Type 2

41. Q&A – DM, type 2

42. Gestational Diabetes Mellitus, GDM
DM associated with pregnancy
Cause:
Elevated levels of estrogen and progesterone make target cells temporarily insulin resistant
Placenta releases insulinase thus accelerating rate of…
Results in temporary, DM Type 2 (usually NIDDM)
Infants often large… (11-13 lbs) and delivered by C-section
Why?
Normal source of insulinase is liver.

43. What if…? 1) You have DM, Type 1
You binge on carbs for several days but do not take your insulin

44. What if…? You have DM, Type 1
You give yourself an insulin injection but do not eat your meal.

45. What if…?
You are not diabetic but you go on a “zero carb” diet

46. What if…?
4. You have DM, Type 2, NIDDM. It’s Thanksgiving, and you have sweet potatoes with brown sugar, pumpkin pie, cherry pie, and lemon meringue pie.

47. What if…?
5) You have a tumor inhibiting release of ADH

48. Control of Blood Glucose by Cortisol
a.k.a. Hydrocortisone
Source: adrenal cortex
Target: many body cells / tissues
Effects:
1) Gluconeogenesis …
2) Lipolysis
3) Proteolysis
4) Vasoconstriction, therefore  BP
5) Anti-inflammatory and therefore anti-immune
Note: Steroid medications mimic some of the effects of cortisol.
Pts. on steroids:
 blood glucose
 Weight gain
 Immune function

49. Q & A

50. Backup of 5 slides on the “What ifs?” Of DM types I & II
These slides have bulleted answers. Slides posted for Students do not.

51. What if…? 1) You have DM, Type 1
You binge on carbs for several days but do not take your insulin
Hyperglycemia, polyuria, polydipsia, polyphagia
possible DKA, pH
Depressed CNS activity, possible Diabetic Coma
Death
Gradual onset

52. What if…? You have DM, Type 1
You give yourself an insulin injection but do not eat your meal.
Hypoglycemia
LOC, shakes, fatigue, nausea, headache, blurred vision, aggressive/combative, syncope
Unconsciousness (may develop very quickly to this)
a.k.a. Insulin shock

53. What if…? You are not diabetic but you go on a “zero carb” diet
Carbs intake  so hypoglycemia
Pancreas releases glucagon
Liver does glycogenolysis & releases G to blood
Insulin release  to “save” G for brain
Skeletal muscle forced to burn FAs. Therefore…
Ketoacidosis. Therefore…
electrolyte imbalances (esp. Na+ and K+) due to being flushed out w ketones
N&V
CNS depression
Coma
Death

54. What if…?
4. You have DM, Type 2. It’s Thanksgiving, and you have sweet potatoes with brown sugar, pumpkin pie, cherry pie, and lemon meringue pie.
Hyperglycemia for 1-2 days
So what?

55. What if…? Pee out lots of dilute urine = Polyuria
5) You have a tumor inhibiting release of ADH
Pee out lots of dilute urine = Polyuria
Blood becomes concentrated = Dehydration
Blood volume is low so BP is low
Thirst increases = Polydipsia
Known as diabetes insipidus

56. Regulation of ECF [K+], [Na+], BV, and BP by Aldosterone
Fig 16.14
Source…
Target...
Effects… next slide

57. 3 effects of aldosterone:
1.)  ECF [K+] and/or [H+] by  secretion of K+ (and H+) at kidneys
2.)  ECF [Na+] by  reabsorption of Na+
Amt. of Na+ in ECF is 1o electrolyte affecting volume of ECF
But… no Na+ receptors/monitors
Na+ and K+ have predictable, inverse relationship …
[K+] is monitored by adrenal cortex…
If [K+] is high then [Na+] _____
If [K+ ] is low then [Na+] _____
Na+ attracts water by osmosis, so…
3.)  BV and BP

58. 3 triggers for the release of aldosterone
Fig 16.15
In order of influence:
#1 – in response to low BP
#2 – in response to high K+
#3 – in response to prolonged stress

59. Cushing’s Syndrome Fig 16.15
Result of excess cortisol (hypercortisolemia)
Usually also comes with excess aldosterone
Therefore excess ______ retained
S&S:
Swollen/puffy “moon face”
“buffalo hump” due to redistribution of fat to upper back
Hyperglycemia (“steroid diabetes”) because cortisol  gluconeogenesis
protein loss from muscle and bone because…
Leads to bone fractures
HTN because…
poor wound healing &  infections because cortisol is anti-inflammatory
Before During
Fig 16.15

60. Cushing’s cont’d
Stretch marks due to redistribution of fat to abdomen
Causes:
#1 use of oral corticosteroid meds
#2 tumor of ant. pit. --  [ACTH]
#3 tumor of ad. cortex --  [cortisol]
#4 cancer of lungs, pancreas, or kidneys --  [ACTH]
Trtmt:
Discontinue the causative med
Surgical removal of cause (tumor)

61. Addison’s Disease
Usually involves  aldosterone and  cortisol (mineralocorticoid) (glucocorticoid)
S&S:
“bronzing” of the skin
Weight loss
Hyponatremia
Hyperkalemia
Dehydration
Low BP
Trtmt:
Corticosteroid meds

62. Response to Short term stress Response to Long term stress
Fig 16.16

63. Effects of Melatonin on Sleep / Wake Cycle

64. Q&A

65. Q & A

66. Q & A

67. Q & A

68. Q & A

69. Q&A

70. Q & A

71. Q & A

72. Q & A