Endocrine 1

The endocrine and central nervous system (CNS) integrate to control and direct the body's metabolic make-up and maintain homeostasis. This system consist of a complex organization of specialized cell clusters or glands. These glands collect, produce, and secrete hormones. This special chemical substance or hormone circulates through-out the body maintaining equilibrium and regulating growth and development.





Hypothalamus

The Hypothalamus is the hub of integration for the endocrine and autonomic (involuntary) nervous center. This gland of importance regulates the endocrine glands by neural and hormonal pathways.

Posterior Pituitary & "H"

"H" links the neural pathways to the posterior pituitary. This neural stimulation causes the posterior pituitary to secrete 2 hormones:
*Anti-diuretic Hormone (when secreted-body retains fluid)
*Oxytocin (in labor-stimulates uterine contraction, while breast-feeding- stimulates the "let down reflex." )

In addition, "H" regulates the level of secretion of effector hormones from the posterior pituitary:
*Growth hormones (GH)
*Prolactin

Anterior Pituitary & "H"

"H" maintains hormonal control over the anterior pituitary gland by allowing an increase or decrease of hormones. This form of gate keeping helps "H" regulate the activity of the anterior pituitary gland to secrete 4 types of trophic hormones:
* Adrenocorticotropic hormone (ACTH)
* Thyroid-stimulating hormone (TSH)
*Luteinizing hormone
* Follicle-stimulating hormone

Archer, E., Berger, N., Clark, S., Daack-Hirsh, S., Fedorov, E., Lemonde, M., Lewis, G., Luft, K., McGuire, M., Tilghman, J., & Walsh, C., (2006) Pathophysiology made incredibly easy. Ambler, PA. Lippincott, Williams, & Wilkins.

Characteristics of hormone regulation:

Control:
the hypothalamic-pituitary axis regulates many hormones

Feedback:
hormones function within feedback loops

Pattern:
hormones exhibit patterns of secretions, metabolism, and elimination

Receptor binding:
hormone attraction and attachment to cells essential to exert and effect

Braun, C., & Anderson, C.,(2007). Pathophysiology-Functional Alterations in Human Health. Philadelphia, PA, Lippincott, Williams, & Wilkins.


Regulation of Hormone Release:

In order to continue on in a state of homeostasis, the body responds to the ever-changing hormonal levels by performance of the negative or positive feedback system. This feedback system is an accurate, or detailed form of measurement and control of the cellular surroundings.


Negative Feedback Loop

• most common
• occurs before increasing hormone volume nullifies the beginning stages of hormone level changes.

The interaction between the hypothalamus and pituitary (hypothalamic-pituitary axis) is a negative feedback control system. The hypothalamus receives input from virtually all other areas of the CNS and uses it to provide input to the pituitary. In response, the pituitary releases various hormones that stimulate certain endocrine glands throughout the body. Changes in circulating levels of hormones produced by these endocrine glands are detected by the hypothalamus, which then increases or decreases its stimulation of the pituitary to maintain homeostasis.

Negative Feedback Loop





From Simple:
Simple feedback occurs when the level of one substance regulates secretions of hormones (simple loop). For example, a low serum calcium level stimulates the parathyroid gland to release parathyroid hormone (PTH). PTH, in turn promotes resorption of calcium. A high serum calcium level inhibits PTH secretions.

To Complex:
When the hypothalamus receives feedback from target glands, the mechanism is more complicated (complex loop) Complex feedback occurs through an axis established between the hypothalamus, pituitary gland and target organ. For example, secretion of the hypothalamic corticotropin-releasing hormone stimulates the release of pituitary corticotropin, which in turn stimulates cortisol secretion by the adrenal gland (target organ). A rise in serum cortisol levels inhibits corticotropin secretion by decreasing corticotropin-releasing hormone.

Above 2 paragraphs:
Archer, E., Berger, N., Clark, S., Daack-Hirsh, S., Fedorov, E., Lemonde, M., Lewis, G., Luft, K., McGuire, M., Tilghman, J., & Walsh, C., (2006) Pathophysiology made incredibly easy. Ambler, PA. Lippincott, Williams, & Wilkins.

See Figure 17-2 & 3


Positive Feedback Loop

• Rare in endocrine system
• occurs when hormone secretions continues to generate added hormone production.

Hypothalamic-Pituitary System

Stimulating Factors

Endocrine Glands

Eptopic production of Hormones-----Hormones-----Feedback Loop

Tissue Receptors

Intracellular Communication

Cell Responses

Heuther, S. (2000) Understanding Pathophysiology Online. Retrieved January 1, 2008 from http://evolvels.elsevier.com/section/default.asp?id=0334%5F

Endocrine Dysfunction

The above glands and hormones function in a complicated manner with feedback loops that assess the level of hormones within the body's system and will increase or decrease the amount necessary for the body to maintain a state of homeostasis. This delicate balance of the hormonal regulation may display dysfunction by:

1)Over- or under stimulation by the hypothalamic pituitary system

2)Primary dysfunction of the gland itself resulting in over- or underproduction of hormone

3)Altered rate of degradation of the hormone

4)Altered responsiveness of the tissues to hormones

5)Ectopic production of hormone


To assist in identifying a complex endocrine system dysfunction, one must be aware of the basic hormonal abnormalities. The ever-changing increasing and decreasing levels of hormones throughout the body result from various causes. Endocrine dysfunction is diagnosed by the failure to produce adequate or over produce a hormone for synthesis or release within the body. Once the hormone is released, possibility of alterations in rate, amount, and activity may change the response the hormone receives once it reaches the target organ. These cell-tissue responses have been identified as receptor-associated and intracellular alterations

Failure of the Tissue Responses

Tissues can fail to respond to hormonal stimulation because of two major types of cellular dysfunction:

Receptor-associated disorders:

Cells that are responsive to hormones have surface or cytoplasmic receptors that bind to a hormone and initiate message delivery to the nucleus.
Defects in these receptors may involve a decrease in the number of receptors or may be the result of molecular changes in receptor structure that alter the sensitivity of the receptor to hormonal binding.
In some instances, antibodies to receptors can block hormone binding and thus decrease or inappropriately increase receptor function.
In some cancer cells, an increase in receptors for growth-inducing hormones may increase cell division and tumor growth.

Intracellular disorders:

Once hormone binding has occurred, cellular response to that hormone is dependent on message delivery to the nucleus of the cell.
This message is delivered by a variety of “second messengers” such as cyclic AMP. In some disorders, this second messenger is not adequately stimulated by receptor binding. In cancer, there may be an exaggerated second messenger response that contributes to nuclear activation and tumor growth.

Last 2 paragraphs taken from:
Heuther, S. (2000) Understanding Pathophysiology Online. Retrieved
January 1, 2008 from http://evolvels.elsevier.com/section/default.asp?id=0334%5F


The above dysfunctions must be recognized by alterations in feedback systems of the endocrine system .

The endocrine system coordinates functioning between different organs through hormones, which are released into the bloodstream from specific types of cells within endocrine (ductless) glands. Once in circulation, hormones affect function of the target tissue. Some hormones exert an effect on cells of the organ from which they were released (paracrine effect), some even on the same cell type (autocrine effect). Hormones can be peptides of various sizes, steroids (derived from cholesterol), or amino acid derivatives.

Hormones bind selectively to receptors located inside or on the surface of target cells. Receptors inside cells interact with hormones that regulate gene function (eg, corticosteroids, vitamin D, thyroid hormone). Receptors on the cell surface bind with hormones that regulate enzyme activity or affect ion channels (eg, growth hormone, thyrotropin
Above 2 paragraphs from:
Merck Manual, (2005). Introduction: Principles of Endocrinology. Retrieved January 1, 2008, from http://www.merck.com/mmpe/sec12/ch150/ch150a.html


There are 9 endocrine glands. They are as follows:

1.Anterior Pituitary
2.Posterior Pituitary
3.Thyroid
4.Parathyroid
5.Pancreas
6.Adrenal Cortex
7.Adrenal Medulla
8.Testes
9.Ovaries

and the Pineal Gland.

Each of these 9 glands collect, produce and secrete one or more hormones as needed.


Gland

1.Ant. Pituitary
1.Thyroid Stimulating Hormone
Target Organ: Thyroid Gland
2.Adrenocorticotropic Hormone (ACTH)
Target Organ: Adrenal Cortex
3.Follicle Stimulating Hormone (FSH)
Target Organ: Reproductive Organs
4.Luteinizing Hormone (LH)
Target Organ: Reproductive Organs
5.Prolactin
6.Growth Hormone (Somatotropic)
Target Organ: Bone, Muscle, Organs and other Tissue
7.Melanocyte Stimulating Hormone (MSH)

2.Post. Pituitary
1.Oxytocin
Target Organ: Uterine & Breast
2.Antidiuretic Hormone (ADH) (vasopressin)
Target Organ: Kidney

3.Thyroid Hormone
1.Thyroxine (T4) & Triiodothyronine (T3)
Target Organ: Multiple Targets
2.Calcitonin

4.Parathyroid
1.Parathyroid Hormone (PTH)
Target Organ: Bone, Blood

5.Pancreas
1.Insulin
Target Organ: Blood Glucose
2.Amylin
3.Glucagon
Target Organ: Blood Glucose
4.Somatostatin

5.Adrenal Cortex
1.Glucocorticoids
1.Cortisol
Target Organ: Multiple Targets
2.Mineralocoids
1.Aldosterone
Target Organ: Kidney
3.Adrenal
1.Estrogens & Androgens

6.Adrenal Medulla
1.Epinephrine (adrenaline)
2.Nor-epinephrine
Target Organ: Sympathetic Nervous System

7.Testes
1.Testosterone
Target organ: Reproductive organs

8.Ovaries
1.Estrogen
Target Organ: Reproductive Organs
2.Progesterone
Target Organ: Reproductive Organs

and Pineal
-Melatonin


Hormone Communication

Hormones travel and influence distant tissues and organs throughout the body via the circulatory system, portal pathways or local cells. There are 5 routes of cell-to-cell communication that the endocrine system utilizes to mediate cell to hormone responses.

1.Endocrine: cells produce and secrete hormones that travel withing the bloodstream to a target organ.

2.Paracrine: cells produce and secrete hormones to local cells. These hormones carry the correct receptor and produce and effect on the system. However, the receptor cell is unable to produce the hormone due to activity on different neighboring cells.

3.Autocrine: same as pancrine except the receptor cell is able to produce the hormone, and acts on like cells.

4.Synaptic: hormones are produced within the neuron, moves along the axon to the synaptic point where it is released. The hormone is then carried away by the co-synaptic axon that has the correct receptors and influences the body's reactions.

5.Neuroendocrine: same as above, except after the synaptic action is carried into the circulatory system to distant cells that have the correct receptors and provide and influence throughout the body.

Braun, C., & Anderson, C.,(2007). Pathophysiology-Functional Alterations in Human Health. Philadelphia, PA, Lippincott, Williams, & Wilkins.

Hormone Receptors: water-soluble & some steroid hormones located in plasma membrane of cells.

Signals/Communication:

Simple Explanation:
A hormone that is secreted into the bloodstream and travels to the target organ is called: 1st-messenger. Each hormones (chemical transmitter) carries identification or a chemical message that interacts with the receptor on the cell. For example, the hormone is the key that is inserted into the receptor cell lock in the plasma membrane. The key insertion into the lock triggers a signal that generates a 2nd messenger within the target cell that activates the cytoplasm and nucleus into a mode recognition and mediates the effect of the hormone on the target cell. Thus, the 2nd messengers control the actions and products of a particular cell.

Huether, S., & McCance, K., Understanding Pathophysiology. (2000). (3rd ed) St. Louis, MO. Lippincott, Williams, & Wilkins.




Hormone Transportation
Hormones are transported throughout the body via the circulatory system.

Water Soluble

Protein (peptide) hormones, such as:

• insulin
• pituitary
• hypothalamic
• PTH
• circulates free forms (unbound)
• Have 1/2-life of seconds to minutes due to--exposure to catabolizing enzymes
• Mediate short-acting responses
• Bind to cell surfaces
• Only free hormones can signal a target cell
  

Lipid Soluble

Hormones:

• cortisol
• adrenal
• androgens
• estrogens
• Circulates in bound form-bound to a carrier or transport protein
• Remain in bloodstream for hours to days
• Mediate rapid and long-acting responses
• Bind to plasma membrane receptors or diffuse through cellular plasma membrane & bind to cytosolic or nuclear receptors.
  

Huether, S., & McCance, K., Understanding Pathophysiology. (2000). (3rd ed.) St. Louis, MO. Lippincott, Williams, & Wilkins

Hormonal Rhythms

Circadian
Pulsatile
Diurnial
Infradian

Huether, S., & McCance, K., Understanding Pathophysiology. (2000). (3rd ed.) St. Louis, MO. Lippincott, Williams, & Wilkins.




Diseases of the Endocrine System

Alterations of the endocrine system are due to the inadequate release of hormone activity. Disorders may be cause dysfunction of the anterior or posterior pituitary or both.

Diseases to be Discussed:

Syndrome of Inappropriate Antidiuetic Hormone (SIADH)
Diabeties Insipidis or Diabetes Mellitus
Pituitary Adenomas
Acromegaly
Prolactinoma
Graves Disease
Factitious Hyperthroidism
Thyroid Storm
Primary & Secondary Hypothyroidism
Thyroid Carcinoma
Primary Hyperparathyroidism
Cushing
Primary & Secondary Hyperaldosteronism
Addison Disease
Pheochromocytoma

Syndrome of Inappropriate Antidiuretic Hormone (SIAH)

1.Life-threatening (disturbs fluid-electrolyte balance).

2.Occurs when an increase of antidiuretic hormone secretions are stimulated by stimuli that increases extracellular fluid osmolarity and decreased extracellular fluid volume; reflects hypotension.

3.SIADH is common complication of surgery (pituitary surgery) critical illness, small cell cancer of the lung, or from brain injury.

4.As a side effect of certain drugs such as anesthetics and opiates.

5.May develop in children during acute phase of meningitis.

6.PROGNOSIS—varies with degree of illness and speed of disease development.

1.Usual resolves w/i 3 days of effective treatment.


SIADH results in:

• renal retention of water without salt
• thus intravascular solutes are diluted.

How does this happen?

In the presence of excessive ADH
Excessive H2O reabsorption from the distal convoluted tubule and collecting ducts causes hyponatremia & normal to sl. increased of extracellular fluid vol.

Causes:

1.Oat Cell CA of the lungs (secretes excessive ADH)
2.Pancreatic or prostate CA
3.Hodgkin's disease
4.CNS disorders
5.Pulmonary disorders
6.Certain drugs
7.Thymonas
8.Myxedema
9.Psychosis

Signs & Symptoms:

1.Fatigue-lethargy-anorexia--thirst--1st s/s
2.Vomiting
3.Intestinal cramping
4.Wt gain
5.Edema
6.Water retention
7.Decreased urine o/p
8.Restlessness
9.Confusion
10.Headache
11.Irritability
12.Seizures
13.Coma
14.Decreased deep tendon reflexes

Pathophysiology Made Visual (2008) Endocrine System. Philadelphia, PA, Lippincott, Williams, & Wilkins.

Diabeties Insipidis or Diabetes Mellitis

Type 1 Type 2
Age of onset Childhood onset Adult onset (usually)

Frequency 10% of all cases of DM 90% of all cases of DM

Gender Male = female Female > male

Race Whites at greatest risk Native Americans, Hispanics,
blacks at greatest risk

Body weight Normal or underweight Overweight

Etiology Autoimmune + genetic causes
Environment (diet) + genetic causes

Pathophysiology Islet cell antibodies with decreased
or absent insulin production
Insulin resistance with increased
hepatic production of glucose


Symptoms Symptoms: polydipsia, polyuria, polyphagia,
fatigue, visual changes,increased infections,
paresthesias
Same as for type 1

Complications Vascular disease, renal disease, heart disease,
neurologic disease, eye disease, infection, ketoacidosis
Same as Type 1 except Ketoacidosis is rare
(hyperosmolar nonacidotic disease may occur)

Laboratory Hyperglycemia, increased hemoglobin A1C, islet cell
antibodies, low or absent insulin levels
Hyperglycemia, increased hemoglobin A1C, increased or normal insulin

Treatment Insulin, meal planning Diet, weight loss, exercise, hypoglycemic agents,
insulin only as last resort
2005 Elsevier Inc.