The Endocrine System

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

Hs are “receptor specific”

Magnitude of response is affected by: 1) 2)

Up Regulation & Down Regulation

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

Hypothalamic Control of the Pituitary Gland Fig 16.5

Hypothalamic Control of the Pituitary Gland Fig 16.5

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

Control of ECF Osmolality (and volume) by ADH

Control of ECF Osmolality (and volume) by ADH “Osmolality” is concentration based on # of solutes per Kg of water. normal range = 280-300 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

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

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

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

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

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???

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

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

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

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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

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

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

Effects of Chronic Hyperglycemia

Why is diabetes (and hyperglycemia) so common?

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…

Side by Side Comparison

Control of Blood Glucose Fig 16.19

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)

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…

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)

Q&A – DM, Type 1

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

Diabetes Mellitus – Type 2 (cont’d) The DM Type 2 epidemic In 2010 11% of adults in North America By 2050 28% “ “ “ “ 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

Q&A – DM, type 2

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.

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

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

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

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.

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

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

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

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

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

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

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?

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

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

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

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

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

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)

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

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

Effects of Melatonin on Sleep / Wake Cycle

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