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 feedback
circuits.
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
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.
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:
Called “Gigantism” in children
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.
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 Goiter
Iodine deficiency – no TH synthesis – no feedback - ↑TSH
Cretinism (↓TH)
Congenital hypothyroidism
Myxedema (↓TH)
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 -