Homeostasis

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Homeostasis Controls

• Successful compensation
• Homeostasis reestablished
• Failure to compensate
• Pathophysiology
• Illness
• Death

Figure 1-5 Homeostasis
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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.

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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.
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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

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

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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

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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 glands 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
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 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
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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.

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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 ? FFAs 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

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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

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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.
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Endemic Goiter
Iodine deficiency no TH synthesis no feedback
- ?TSH
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Cretinism (?TH)
Myxedema (?TH)
Congenital hypothyroidism
Adult hypothyroidism
22
Graves 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 Ca2
• renal calculi

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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.

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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

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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)

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Addisons 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

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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 Graves disease (autoimmune
  thyroid)
• Up-regulation -