90

Clinical Application: Hyperparathyroidism

!  Parathyroid adenoma #1 cause !  Serum calcium imbalance

!  Paired, pyramid shaped, on superior surface of kidney

!  Retro-peritoneal

!  2 regions: !  Medulla !  Cortex

!  5 layers

Adrenal Glands (Suprarenal)

adrenal gland

92

Anatomy & Hormones of the adrenal glands

!  2 structurally & functionally distinct areas !  Adrenal cortex

!  Mineralocorticoids affect mineral homeostasis

!  Glucocorticoids affect glucose homeostasis

!  Androgens have masculinzing effects

!  Adrenal medulla !  Modified sympathetic

ganglion of ANS !  Intensifies sympathetic

responses

!  Epinephrine & norepinephrine

93

Describe the function of aldosterone:

!  Aldosterone is the major mineralcorticoid

!  Functions: !  Regulate electrolyte concentration in ECF

!  increase reabsorption of Na+ w/ Cl-, bicarbonate & H2O following it

!  promotes excretion of K+ & H+

!  Secretion regulated by the renin-angiotensin pathway (RAA)

94

Explain the RAA Pathway:

95

Clinical Application: Hyperaldosteronism or Conn Syndrome !  Cause of primary aldosteronism = adrenal adenoma in

80% of patients

!  Sx = HTN, hypokalemia

!  Tx = removal of adenoma !  Corrects HTN & hypokalemia

in most patients

MRI in a patient with Conn syndrome showing a left adrenal

adenoma.

http://www.ispub.com/journal/the_internet_journal_of_surgery/volume_24_number_1_1/article/conn-s-syndrome

96

Describe the function of cortisol:

!  95% of glucocorticoids hormonal activity is due to cortisol

!  Functions !  Help regulate metabolism

!  Protein catabolism & lipolysis

!  Gluconeogenesis

!  nutrients available for ATP production

!  Resistance to stress

!  Anti-inflammatory (Hydrocortisone cream)

!  Immunosuppression (Corticosteroids such as prednisone)

97

Describe how glucocorticoids are regulated:

! Negative feedback

!  Controlled by CRH (corticotropin releasing HM) & ACTH (adrenocorticotropic HM) from anterior pituitary

98

Good Summary

Figure 17.21 pg

683

2 3

1

3

5

4

High doses of cortisol: Increase retention of Na+, H2O

4 5 6

6

7 8

1 2

Stimulation Inhibition

Cortisol

STIMULUS

CONTROL CENTER

The hypothalamus releases corticotropin- releasing hormone (CRH) into the hypothalamo-hypophyseal portal system.

RECEPTOR

Hypothalamus responds to various stimuli.

In response to CRH, the anterior pituitary releases adrenocorticotropic hormone (ACTH).

ACTH stimulates the adrenal cortex to release glucocorticoids (e.g., cortisol) into the blood.

Cortisol stimulates target cells (effectors).

Cortisol levels increase inhibiting release of CRH and ACTH.

NET EFFECT

Increase of all nutrients in the blood.

Cortisol

EFFECTORS: Effectors respond to cortisol in the following ways:

Liver

Stimulation of protein catabolism (occurs in all cells except hepatocytes)

Stimulation of lipolysis Inhibition of lipogenesis

Stimulation of gluconeogenesis (use amino acids and fatty acids)

Adipose connective tissue

All cells

ACTH

CRH

Hypothalamus

Variables that act on the hypothalamus: • Negative feedback by cortisol • Time of day • Stress

Decrease inflammation Suppress the immune system Inhibit connective tissue repair

Cortisol bound by carrier proteins (e.g., CBG)

Amino acids Glucose Amino acids

Glycerol fatty acids

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Fig. 17.22

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Cortisol levels fluctuate throughout the day. Notice that in a normal sleep-wake cycle, peak levels of cortisol correspond to the late stages of a normal sleep cycle. About half of all cortisol release occurs when you are asleep, with cortisol levels peaking right before waking in the morning. This rhythm of release is regulated by light and dark cycles detected by the retina as nerve signals are relayed to the hypothalamus. (Between individuals, there is significant variation in normal levels.)

Perc

ent d

evia

tion

from

the

mea

n

0 0 8

Both emotional stress (e.g., anxiety, anger, fear) and physical stress (e.g., fever, trauma, or intense exercise) increase the release of cortisol.

150

100

50

–50

–100 24 16

Hours

(a)

(b)

Cortisol level is increased by stress.

Cortisol release fluctuates based on the time of day (circadian rhythm).

24 hours

Sleep

101

Clinical Applications: !  Hyperadrenocorticism or

Cushing’s Disease !  Etiology - Usually excess

ACTH due to pituitary tumor

!  Sx

!  Hypocorticism or Addison’s Disease !  Etiology – genetic or

autoimmune

!  Sx

102

Recall the role of androgens: !  DHEA

!  Insignificant in males !  Important in females

!  Libido !  Converted to estrogen

!  Clinical Application: !  Congenital Adrenal Hyperplasia

http://www.dshs.state.tx.us/newborn/cah2.shtm

Page 682

104

Characterize the role of the adrenal medulla:

!  Chromaffin cells secrete epinephrine &

norepinephrine

!  Hormones are sympathomimetic (Mimic SNS

effects)

!  Enhance fight or flight response

105

Characterize the pancreas:

!  Location

!  Consists of acinar & islet cells

!  Both endocrine & exocrine in function

Page 686

107

Endocrine & exocrine

functions of the pancreas:

!  Acinar cells = exocrine

(99% of cells)

!  Pancreatic islets (islets of Langerhans) = endocrine !  Alpha (!) cells - glucagon !  Beta (") cells - insulin !  Delta cells – somatostatin

(aka GIH, Growth Inhibiting Hormone)

!  F cells - pancreatic polypeptide

4

5 2 3 4

1 2 3

Insulin

Pancreas Stimulation Inhibition

NETEFFECT

Decreased blood glucose (fatty acids and amino acids are also decreased in the blood)

CONTROL CENTER

Beta cells within pancreas release insulin.

Beta cells within the pancreas detect an increase in blood glucose levels.

RECEPTOR

Insulin stimulates target cells (effectors).

Insulin Negative feedback Insulin release is inhibited as blood glucose levels decrease to normal.

Insulin

Liver tissue Most cells

Increased uptake of glucose by increasing glucose transport proteins in the plasma membrane

Increased uptake of amino acids, which stimulates protein anabolism

Increased lipogenesis Decreased lipolysis

Increased glycogenesis Decreased glycogenolysis and gluconeogenesis

Adipose connective tissue All cells (especially muscle)

1 STIMULUS

Increase in blood glucose

EFFECTORS: Effectors respond to insulin in the following ways:

Glucose Glucose

Amino acids Fatty acids

5 2 3 4

1 2 Glucagon

STIMULUS

Decrease in blood glucose

Pancreas

CONTROLCENTER

Alpha cells within the pancreas release glucagon.

RECEPTOR

Alpha cells within the pancreas detect a decrease in blood glucose levels.

Gucagon stimulates target cells (effectors).

Glucagon

Increased blood glucose and fatty acid levels (note—no change in amino acids or proteins).

NET EFFECT

Negative feedback Glucagon release is inhibited as blood glucose levels increase to normal.

Glucagon

Adipose connective tissue Liver

Increased glycogenolysis and gluconeogenesis Decreased glycogenesis

Increased lipolysis Decreased lipogenesis

3 Glucose

Glycerol fatty acids

4 EFFECTORS: Effectors respond to glucagon in the following ways:

Stimulation Inhibition

1

110

Serum glucose levels are regulated by glucagon & insulin secretion:

111

Clinical Application: Diabetes Mellitus !  May be caused by too little insulin, resistance to insulin, or both

!  There are three major types of diabetes: !  Type 1 diabetes - usually diagnosed in childhood

!  Body makes little or no insulin

!  Cause - ?? Genetics, viruses, & autoimmunity

!  Type 2 diabetes - more common than type 1 !  Usually occurs in adulthood – linked to obesity lack of exercise

!  Pancreas does not make enough insulin or cells exhibit insulin resistance

!  Gestational diabetes - high blood glucose during pregnancy

!  Hyperglycemia can cause several problems: !  Excessive thirst (polydipsia)

!  Frequent urination (polyuria)

!  Hunger (polyphagia)

!  Fatigue

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113

Gonads produce gametes & hormones: Ovaries

!  Ovaries:

!  Produce estrogen

!  Produce progesterone

!  Estrogen & progesterone along w/ FSH & LH regulate

menstrual cycle, maintain pregnancy, prepare mammary

glands for lactation, maintain female 2o sex characteristics

!  Produce inhibin inhibits FSH secretion

!  Produce relaxin during pregnancy

114

Gonads produce gametes & hormones: Testes

!  Testes

!  Produce testosterone

!  Regulate sperm production

!  Maintains male sexual characteristics

!  Produce inhibin which inhibits FSH

115

Recall the role of follicle stimulating hormone (FSH)

!  “Gonadotropins” = FSH & LH

!  anterior pituitary release FSH

!  initiates formation of follicles

!  stimulates estrogen secretion

!  stimulates sperm production

116

Role of luteinizing hormone (LH)

!  Produced the anterior pituitary

!  In females it induces: !  Ovulation

!  Formation of corpus luteum !  Secretion of progesterone & estrogen

!  In males it: !  stimulates secretion of testosterone

117

Characterize the pineal gland: !  Attached to roof of 3rd ventricle of brain

!  Secretes melatonin !  Maintains Circadian rhythms

!  More melatonin liberated during darkness than light

!  Linked to seasonal affective disorder (SAD)

118

III. The Stress Response ! What is Stress? ! Eustress vs.

Distress ! Body’s

homeostatic mechanisms attempt to counteract stress

Page 685

120

Describe the stress response: !  Stressful conditions can result in the stress response

or general adaptation syndrome (GAS)

!  3 stages: flight-or-fight, resistance reaction, exhaustion

121

1. Alarm (Fight-or-Flight)

!  Initiated by hypothalamic stimulation of sympathetic portion of ANS & adrenal medulla (epinephrine & norepinephrine) !  Nonessential fxns (SLUDD)

inhibited ! decreased blood flow to kidneys ! release of renin ! RAA ! aldosterone ! H2O retention & increased BP

122

123

2. Resistance Reaction

!  Initiated by hypothalamic releasing HM !  corticotropin,

growth hormone & thyrotropin releasing hormones

!  Results !  Allow body to

continue to fight a stressor

124

125

3. Exhaustion !  Effects of prolonged exposure to cortisol & other

resistance reaction HM:

!  Wasting of muscle

!  Immunosuppression

!  Ulceration of GI tract

!  Failure of beta cells

!  Insulin resistance

126

Stress can lead to disease: !  Gastritis, Ulcerative colitis,

IBS, Peptic ulcers

!  Cardiovascular disease

!  Migraines

!  Asthma

!  Increased incidence of

infectious and autoimmune diseases

!  Anxiety / depression

!  Post traumatic stress syndrome

127

IV. Aging and the Endocrine System !  Production of hGH decreases

!  Production of T3/T4 decreases ! increased TSH

!  Thymus atrophies after puberty replaced w/ adipose

!  PTH levels increase (decreased Ca+2 intake), calcitonin levels decrease ! osteoporosis

!  Adrenal glands produce less cortisol & aldosterone

!  Receptor sensitivity to Glc declines

!  insulin secreted more slowly

!  Ovaries no longer respond to gonadotropins