1. Homeostasis & Controls
Successful compensation
Homeostasis reestablished
Failure to compensate
Pathophysiology
Illness
Death
Figure 1-5: Homeostasis

2. Regulation of hormone secretion
Sensing and signaling: a biological need is sensed, the endocrine system sends out a signal to a target cell whose action addresses the biological need. Key features of this stimulus response system are:
·        receipt of stimulus
·        synthesis and secretion of hormone
·        delivery of hormone to target cell
·        evoking target cell response
·        degradation of hormone

3. Signal Pathways Signal molecule (ligand) Receptor Intracellular signal
Target protein
Response

4. Target tissue response will generally be determined by two factors:
Plasma Concentrations
Normally, the greater the concentration, the greater the response (up to receptor saturation).
• The number of cell membrane receptors
More receptors obviously result in a greater response.

5. Control of Endocrine Activity
Concentration of hormone in blood and extracellular fluid.
Almost inevitably, disease results when hormone concentrations are either too high or too low, and precise control over circulating concentrations of hormones is therefore crucial.
Control of hormone concentration:
Synthesis and secretion of hormones are the most
highly regulated aspect of endocrine control. Such
control is mediated by positive and negative feedback
circuits.

6. Negative Feedback
Negative feedback is the primary mechanism through which your endocrine system maintains homeostasis
Secretion of a specific hormone is turned on or off by specific physiological changes (similar to a thermostat)
EXAMPLE: plasma glucose levels and insulin response

7. Feedback Loops

8. Negative Feedback Controls: Long & Short Loop Reflexes
Figure 7-14: Negative feedback loops in the hypothalamic anterior pituitary pathway

9. The responsiveness of a target cell can
also vary by regulating the number of
hormone-specific receptors.
Receptor numbers are usually increased when hormone secretion is low and decreased when hormone secretion is high.
Also, some hormonal responses are increased or decreased by the presence of other (different) hormones.

10. Number of Receptors
Down-regulation: is the decrease of hormone receptors which decreases the sensitivity to that hormone
Up-regulation: is the increase in the number of receptors which causes the cell to be more sensitive to a particular hormone

11. Modulation of Target Cell Sensitivity

12. Endocrine Disorders
Variations in hormone concentration and target cell sensitivity have noticeable effects on the body
Hyposecretion – inadequate hormone release
tumor or lesion destroys gland
head trauma affects pituitary gland’s ability to secrete ADH
diabetes insipidus = chronic polyuria
Hypersecretion – excessive hormone release
tumors or autoimmune disorder
toxic goiter (graves disease) – antibodies mimic effect of TSH on the thyroid

13. Pituitary Disorders Hypersecretion of growth hormones acromegaly
thickening of the bones and soft tissues
problems in childhood or adolescence
gigantism if oversecretion
dwarfism if hyposecretion

14. Acromegaly Called “Gigantism” in children Cause: Symptoms:
Abnormally high amounts of human growth hormone (HGH) from pituitary. Most common cause is a benign tumor in the pituitary.
Symptoms:
1) Rapid growth in height
2) Significantly enlarged hands
and feet
3) Change in appearance of face
4) Headaches
5) Visual problems
6) Can also lead to heart disease,
respiratory disease, arthritis or
diabetes.
Called “Gigantism” in children

15. The endocrine system controls fuel metabolism.
Metabolism is all of the chemical reactions within the cells of the body.
Anabolism is the synthesis of larger organic molecules.
Catabolism is the breakdown of large molecules.
Normally the rates of anabolism and catabolism are in balance in the adult.
Nutrients from meals must be stored and released between meals.
The brain needs a constant supply of glucose.
It cannot store glycogen.

16. Types of Diabetes Mellitus (Pancreatic Disorder)
Type I (IDDM) - 10% of cases - hyposecretion
some cases have autoimmune destruction of  cells, diagnosed about age 12
treated with diet, exercise, monitoring of blood glucose and periodic injections of insulin or insulin pump
Type II (NIDDM) - 90%
- signal transduction pathway
insulin resistance
failure of target cells to respond to insulin
3 major risk factors are heredity, age (40+) and obesity
treated with weight loss program of diet and exercise,
oral medications improve insulin secretion or target cell sensitivity

17. Pathology of Diabetes
Acute pathology: cells cannot absorb glucose, rely on fat and proteins (weight loss + weakness)
fat catabolism  FFA’s in blood and ketone bodies
ketonuria promotes osmotic diuresis, loss of Na+ + K+
ketoacidosis occurs as ketones  blood pH
if continued causes dyspnea and eventually diabetic coma
Chronic pathology
chronic hyperglycemia leads to neuropathy and cardiovascular damage from atherosclerosis
retina and kidneys (common in type I), atherosclerosis leading to heart failure (common in type II), and gangrene

18. Hyperinsulinism
From excess insulin injection or pancreatic islet tumor
Causes hypoglycemia, weakness and hunger
triggers secretion of epinephrine, GH and glucagon
side effects: anxiety, sweating and  HR
Insulin shock
uncorrected hyperinsulinism with disorientation, convulsions or unconsciousness

19. Thyroid Gland Disorders
Congenital hypothyroidism ( TH)
infant suffers abnormal bone development, thickened facial features, low temperature, lethargy, brain damage, cretinism in children
Myxedema (adult hypothyroidism,  TH)
low metabolic rate, sluggishness, sleepiness, weight gain, constipation, dry skin and hair, cold sensitivity,  blood pressure and tissue swelling
Endemic goiter (goiter = enlarged thyroid gland)
dietary iodine deficiency, no TH, no - feedback,  TSH
Toxic goiter (Graves disease)
antibodies mimic TSH, TH, exophthalmos
• Hyperthyroidism causes an
- elevated metabolic rate, high heart rate and exophthalmos
(bug eyes), and usually weight loss.

20. Endemic Goiter
Iodine deficiency – no TH synthesis – no feedback - ↑TSH

21. Myxedema (↓TH) Cretinism (↓TH) Congenital hypothyroidism
Adult hypothyroidism

22. Grave’s Disease
Autoimmune disorder – body makes antibodies to thyroid-stimulating hormone receptor (TSHR)
Results in absence of negative feedback and hyperthyroidism.

23. Parathyroid Disorders
Hypoparathyroid
surgical excision during thyroid surgery
hypocalcemia
fatal tetany 3-4 days
Hyperparathyroid = excess PTH secretion
tumor in gland
causes soft, fragile and deformed bones
 blood Ca+2
renal calculi

24. The endocrine system controls calcium metabolism.
Calcium homeostasis involves immediate adjustments to control calcium in the blood.
The parathyroid hormone (PTH) raises the level of calcium in the blood. (from the bones)
Too much bone loss (release) can weaken bones. (causing Osteoporosis).
The thyroid gland secretes Calcitonin.
It causes bones to absorb calcium from the blood.

25. Calcium disorders can arise.
Hypercalcemia can occur by excess PTH secretion. This reduces the excitability of muscle and nervous tissue. Cardiac disturbances can occur.
Other effects are the thinning of bones and the development of kidney stones.
PTH hyposecretion leads to hypocalcemia. This increases neuromuscular excitability

26. Adrenal Disorders Cushing syndrome is excess cortical secretion
causes hyperglycemia, hypertension, weakness, edema
muscle and bone loss occurs with protein catabolism
buffalo hump & moon face = fat deposition between shoulders or in face
Adrenogenital syndrome (AGS)
adrenal androgen hypersecretion accompanies Cushing syndrome
causes enlargement of external sexual organs in children & early onset of puberty
masculinizing effects on women (deeper voice & beard growth)

27. Addison’s Disease Cause:
Severe or total deficiency of adrenal cortical hormones – primarily cortisol and aldosterone.
Due to destruction of adrenal cortex (autoimmune).
• Symptoms:
Fatigue, weakness in muscles, loss of appetite, weight loss.
Blood pressure is low → lightheadedness.
Irritability and depression.
Loss of cortisol → increase in ACTH → darkening of the skin.
Addisonian Crisis – caused by increase in stress

30. Summary Responsiveness of target cell to hormone depends on:
- Plasma concentrations
*Feedback mechanisms
- hypo- and hyper-secretion of hormone (ex: thyroid)
- Number of receptors
*Down-regulation
- desensitization – prolonged exposure of high levels of hormone
-example: Grave’s disease (autoimmune – thyroid)
*Up-regulation -