Homeostasis & Controls

• Successful compensation– Homeostasis

reestablished

• Failure to compensate– Pathophysiology

• Illness• Death

Figure 1-5: Homeostasis

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

Signal Pathways

• Signal molecule (ligand)

• Receptor

• Intracellular signal

• Target protein

• Response

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.

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 feedbackcircuits.

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

Feedback Loops

Negative Feedback Controls: Long & Short Loop Reflexes

Figure 7-14: Negative feedback loops in the

hypothalamic anterior pituitary pathway

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.

The responsiveness of a target cell can also vary by regulating the number of

hormone-specific receptors.

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

Modulation of Target Cell Sensitivity

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

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

Acromegaly Cause: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 height2) Significantly enlarged hands and feet3) Change in appearance of face4) Headaches5) Visual problems 6) Can also lead to heart disease, respiratory disease, arthritis or diabetes.Called “Gigantism” in children

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.

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

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

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

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.

Endemic GoiterIodine deficiency – no TH synthesis – no feedback - ↑TSH

Cretinism (↓TH) Myxedema (↓TH)

Congenital hypothyroidism Adult hypothyroidism

Grave’s Disease• Autoimmune disorder – body makes

antibodies to thyroid-stimulating hormone receptor (TSHR)

• Results in absence of negative feedback and hyperthyroidism.

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

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.

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

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)

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

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 -