State endocrine glands and their functions.
Characteristics of hormones & hormone transport
1. Control - HPA
3. Patterns of secretion, metabolism, elimination
4. Receptor binding - attraction & attachment
5. Effect on target cells, tissues, organs
Discuss hypothalamic-pituitary system
Provides neuronal control for this important segment of the endocrine system
Produces "releasing/inhibitory" hormones and tropic hormones.
Discuss pituitary gland function & disorders
What is a negative feedback loop?
The way that most hormone levesl in the blood are recognized w/in the hypothalamus & pituitary.
Like a temperature thermostat.
Describe the role of the neuroendocrine system in the stress response
Define anabolism & catabolism
Discuss growth hormone function and disorders
Protein hormone that's released in a diurnal pattern (over 24 hrs).
~70% is released in a burst 1-4 hours after onset of sleep.
GH increases protein synthesis in all body cells, esp. muscle cells.
Discuss growth hormone function and disorders
Compare & contrast Type 1 & Type 2 Diabetes, and gestational diabetes.
Recognize short-term and long term complications of diabetes.
Compare & Contrast Adrenal & Thyroid disorders
What are hormones?
Chemical substances, formed in a tissue or organ that stimulate or inhibit the growth/function of other tissues/organs.
T/F: hormones can be made of carbohydrates.
True. They can vary in composition from single amino acid, to a complex of proteins, carbs or lipids.
6 regulatory functions of homrones
1. energy metabolism
2. growth & development
3. muscle/fat distribution
4. fluid/electrolyte balance
5. sexual development
What is the endocrine system?
A collective group of tissues capable of secreting hormones.
T/F: neurons can release hormones.
True. Neurons & tumor cells can release hormones.
T/F: neurotransmitters like epinephrine, dopamine, serotonin & norepinephrine cannot be categorized as hormones.
False... kinda. They are chemical messengers and they stimulate a response, so they act as hormones do.
Which body systems/functions are integrated into regulatory processes?
What are the 5 factors that characterize hormones?
1. control - hypothalamic-pituitary axis
2. feedback - loops
3. patterns - seen in secretion, metabolism, elmination
4. receptor binding
What aspect of the hypothalamic-pituitary axis (HPA) initiates hormone secretion?
The hypothalamus initiates secretion from its anterior & posterior lobes.
Initiation & regulation of many hormones relies on the HPA.
What are the 2 pathways that hypothalamus-generated travel?
1. through nerve axons to the posterior pituitary. ex - ADH & oxytocin
2. through blood vessels to the anterior pituitary.
Also, some hypothalamic neurons secrete releasing/inhibiting substances through the hypophyseal portal system (blood vessels) to stimulate the anterior pituitary.
hormones that act on anterior pituitary
2. growth hormone-releasing hormone (GHRH)
3. thyrotropin-releasing hormone (TRH)
4. Corticotropin-releasing hormone (CRH)
5. Gonadotropin-releasing hormone (GnRH)
6. Somatostatin (inhibiting)
7. Dopamine (inhibiting)
Volcy: GH, prolactin, TSH, ACTH, FSH, LH
T/F: some hormones are secreted directly from the pituitary w/o stimulation from the hypothalamus.
True. ex - melanocyte-stimulating hormone.
What inputs does the hypothalamus receive to regulate body functions?
2. chemical mediators
What impacts the negative feedback mechanism?
Environmental & body temp
Some hormones are also affected by the presence of the substances they regulate.
What is a positive feedback loop?
Presence of the hormone stimulates increased production of the hormone until the cycle is interrupted.
T/F: many hormones exhibit a predictable pattern of secretion
True. Ex - sex hormones that regulate the menstrual cycle, or GH that increases during sleep and decreases during waking hours.
How is the accumulation of hormones prevented?
Inactivation & elimination.
What is a common mechanisms for inactivation?
Enzymes break down the hormone after attaching to the cell receptor & exerting an effect.
Or in the liver.
How are hormones eliminated?
Through urine or w/ bile (via feces)
How many receptors can cells have?
What is the benefit of receptor binding?
Allows hormones to act selectively on certain cells.
How do autoimmune conditions impact receptor binding?
They reduce the number of receptors.
What is affinity regulated by?
Body fluid pH
What are the 5 major pathways that mediate cell-to-cell communication with respect to hormones?
What is the endocrine pathway?
Hormones are produced in a cell, secreted, and travel through the vascular system to distant cells to exert an effect.
What is the paracrine pathway?
Hormoens are produced in a cell, secreted to nearby cells to exert an effect.
What is the autocrine pathway?
Same as paracrine, except the receptor cell is capable of producing the hormone.
What is the synaptic pathway?
Hormones are produced w/in the neuron, then travel along axon to the synapse. Once released into synapse, they're taken up by a nearby neuron to exert an effect.
What is the neuroendocrine pathway?
Hormones are produced in a neuron, then they travel along the axon to the synapse where they are released and taken up into the vascular system to distant cells to exert an effect.
What is stress?
reactions of the body to forces of a deleterious nature that disturb homeostasis.
What is a stressor?
Any endogenous or exogenous force that causes stress.
What does homeostasis rely on?
The ability to respond adequately to stress. Too little and the body can't defend against the stressor. Too much can lead to the destruciton of body tissue over time.
What 4 CNS structures play a role in the stress response?
How does the brainstem contribute to the stress response?
Coordinates the autonomic nervous system, the cerebral cortex, the limbic system, & the hypothalamus. Produces norepinephrine to enable a quick defense against stressor.
What does the autonomic nervous system do in the presence of a stressor?
Increases heart rate, BP, respiratory rate, pupil dilation & sweating.
Blood flow to the muscles, heart & lungs increases (prep for "fight or flight").
Gastric perfusion & motility decrease.
Why can stress lead to ulcers in the GI tract?
Altered blood flow, decreased oxygenation to tissues & prolonged cortisol exposure can cause ulcers.
How does the cerebral cortex contribute to the stress response?
Coordinates cognitive aspects like focus, planning, attention & persistence.
How does the limbic system contribute to the stress response?
Coordinates emotional aspects like fear, anxiety, anger & excitement. Stimulates reticular activating system.
How does the thalamus contribute to the stress response?
Coordinates sensory input related to stressor.
How does the hypothalamus contribute to the stress response?
Coordinates secretion of releasing hormones to initiate endocrine response; regulates autonomic nervous system response.
How does the reticular activating system contribute to the stress response?
Increases alertness and muscle tension & contributes to stimulation of the autonomic nervous system response.
What begins the endocrine aspect of the neuroendocrine response?
Corticotropin-releasing hormone (CRH) from the hypothalamus & catecholamines from the sympathetic nervous system & adrenal glands. (p. 291)
What is general adaptation syndrome?
Used to describe the neuroendocrine response to a stressor & the corresponding physiologic changes.
What are the 3 stages of GAS?
1. alarm stage
2. resistance stage
3. exhaustion stage
What happens in the alarm stage of GAS?
Preparation stage. Catecholamines & cortisol are released in response to stimulation of the sympathetic nervous system, the hypothalamic-pituitary axis & the adrenal glands.
aka FIGHT OR FLIGHT
T/F: in long-term stress situations, the response may resolve within the alarm stage.
False, only in short-term or mild situations.
Which hormones are suppressed during the alarm stage? Why?
Growth, thyroid & reproductive.
Conserve energy needed to fend off the stressor.
T/F: Antidiuretic hormones is increased during the alarm stage to maintain BP.
T. Perfusion to vital tissues is important.
What happens in the resistance stage of GAS?
In the presence of persistent stress, there is decreased levels of cortisol via negative feedback mechanisms.
Thyroid, growth & reproductive hormones continue to be suppressed. Can impact linear growth, metabolism & reproduction.
Antidiueretic hormone elevation can cause hypertension.
What happens in the exhaustion stage of GAS?
Energy is depleted and tissues degenerate.
T/F: prolonged hypercortisolism exerts no negative effects.
False; leads to impairment of inflammatory & immune responses, tissue breakdown & glucose intolerance.
Why do functional deficits arise the presence of altered hormone function?
impairment of the endocrine gland
lack of hormone synthesis
excessive hormone synthesis
impaired receptor binding
impaired feedback mechanisms
altered cellular response to the hormone
How do hormone malfunctions manifest?
inadequate or excessive production, composition, secretion, receptor binding, uptake, metabolism, or elimination of hormones.
What is hypopituitarism?
A generic term indicating decreased secretion of 1 or more pituitary hormones.
What is hyperpituitarism?
Excess of pituitary hormone secretion.
What is panhypopituitarism?
Deficiency of all anterior pituitary hormones.
What is the range of clinical manifestations seen when the pituitary is damaged?
Loss of thyroid, adrenal & reproductive function, as well as growth problems.
What 11 things can cause impairment of the endocrine glands?
What factors effect receptor binding disorders?
1. decreased # of receptors
2. lack of receptor sensitivity to the hormone
3. presence of antibodies that block receptor sites or occupy the receptor site & mimic the hormone.
4. presence of tumor cells w/ receptor activity that deprive the unaffected cells of the hormone.
What do intracellular disorders involve? What is their usual cause?
Malfunction of the inner mechanisms of the cell. Baton gets dropped once it reaches the cell.
Cause: impaired enzyme or protein production/usage.
At what points along the hypothalamic-pituitary axis can feedback mechanisms fail?
Any point - the secreting gland, the receptors, or target tissues.
T/F: impairment of feedback mechanisms may be a problem of ectopically produced hormone.
Most common ectopically produced hormones are ADH & ACTH.
What is another word for the metabolism of hormones?
What 9 problems can alter hormone function?
T/F: hypopituitarism has a rapid onset.
False. It comes on gradually; clinical manifestations aren't evident until most of the gland has been destroyed.
What are the general manifestations of hypopituitarism?
T/F: urine hormone levels are collected over a 24-hour period.
True, b/c secretion rates can fluctuate over time.
What serum levels can provide indirect info on hormone function?
How are hormone elevations treated?
Remove tumor that is secreting ectopic hormone
Remove all/part of the corresponding endocrine gland
Administer meds that block the effects of the hormone.
How are low hormone levels treated?
Exogenous administration of the specific hormone for the rest of the lifetime.
What is SIADH?
Syndrome of inappropriate antidiuretic hormone. Excessive production & release of ADH, despite changes in serum osmolality & blood volume.
What can transietly increase ADH levels?
stressful stimuli - trauma, exposure to temp extremes, pain conditions, surgery, infection
What is the most common cause of SIADH?
Tumor secretion of ectopic ADH.
How does ADH promote water retention?
Increases the permeability of the nephrons in the kidneys.
Where does body water initially accumulate?
Intracellularly. The CNS is very sensitive to these changes. This is why edema or fluid overload in the vascular system leading to heart failure is uncommon.
What are the clinical manifestations of SIADH?
They're all related to hypotonic hyponatremia.
Once sodium drops to 115-120 mEQ/L:
decreased & concentrated urine output
Once sodium drops to 110 mEq/L:
What are the diagnostic criteria for SIADH?
1. hyponatremia (less than 135 mEq/L)
2. hypotonicity (plasma osmolality less than 280 mOsm/kg)
3. decreased urine volume
4. highly concentrated urine w/ high sodium content.
5. absence of renal, adrenal, thyroid abnormalities.
What is DI?
Diabetes insipidus. Insufficient ADH results in an inability to concentrate or retain water.
What are the 3 major causes of DI?
1. Insufficient production of ADH by the hypothalamus, or ineffective section by the posterior pituitary.
2. Inadequate kidney response to the presence of ADH (aka nephrogenic DI)
3. Ingestion of extremely large volumes of fluids & decreasing ADH levels (water intoxication can be attributed to psychiatric disturbance)
What is the most common specific cause of DI?
Impairment of hypothalamic osmoreceptors after trauma or surgery to a region at/near the hypothalamus.
When is neophrogenic DI most commonly observed?
Chronic renal insufficiency
disease of renal tubules
Rarely it's inherited as an x-linked disorder.
What are the clinical manifestations of DI?
Polyuria and excessive thirst.
Urine is highly dilute w/ low specific gravity.
Serum hyperosmolality & severe dehydration, due to loss of fluids.
Shock and death (if untreated)
How is diagnosis determined?
Careful pt history & physical examination.
dehydration, bladder enlargement, urine specific gravity of 1.005 or less, urine osmolality of 200 mOsm/kg or less
What is hyperthyroidism? What causes it?
State of excessive thyroid hormone.
Results from excessive stimulation of the thyroid gland, disease of the thyroid gland, excess production of TSH by a pituitary adenoma.
In thyroid-sensitive individuals, cough expectorants, health food supplements containing seaweek, iodinated contrast dyes can induce hyperthyroidism.
What is Graves's disease?
Most common cause of hyperthyroidism, most common autoimmune disease in the US.
IgG antibodies bind to the TSH receptor on thyroid cells and stimulate excessive thyroid hormone secretion >> thyroid gland undergoes hyperplasia.
What is thyrotoxicosis?
Presence of excessive thyroid hormone, as in Graves's disease.
T/F: chronic thyrotoxicosis can result in hypothyroidism.
True. It leads to progressive thyroid failure.
What is thyrotoxic crisis?
"thyroid storm" Sudden, severe worsening of hyperthyroidism that may result in death.
What are the clinical manifestations of Graves's disease?
Most are related to enlargement of thyroid & excessive metabolic rate.
irregular menstrual cycle
What is a goiter? What does it occur?
Enlarged thyroid. B/c of follicular epithelial cell hyperplasia.
What is exopthalmos?
Protrusion of the eyeballs, a characteristic finding of Graves's disease. It usually persists despite treatment.
T/F: Men are 7-10x more likely to develop Graves's disease than women.
False. Women are 7-10x more likely.
What are the diagnostic criteria for Graves's disease?
Lab tests - TSH, T3 & T4
Free thyroxine level & increased uptake of radioactive iodine by the thyroid gland confirm the diagnosis.
How is Graves's disease treated?
Destruction of all/part of gland w/ radiactive iodine
Surgical removal of all/part of gland.
What is hypothyroidism? What are the 2 kinds?
Deficient thyroid hormone.
Congeital or acquired.
What is lacking in congenital hypothyroidism?
Lack of thyroid gland development
Lack of appropriate synthesis of thyroid hormone
Problems w/ TSH secretion
T/F: it's apparent immediately after birth that a baby has congenital hypothyroidism.
False; T4 crosses the placenta.
What is cretinism?
Mental retardation & impaired growth resulting from hypothyroidism in the infant.
What 3 things can result in acquired hypothyroidism?
1. deficient thyroid hormone synthesis
2. destruction of the thyroid gland
3. impaired TSH/TRH secretion
What are the common causes of hypothyroidism?
1. autoimmunity (autoimmune processes attack the thyroid gland or block TSH)
2. iodine deficiency
3. surgical removal of or radiation therapy to the thyroid
4. meds that destroy the thyroid
5. genetic defects
What are the clinical manifestations of hypothyroidism?
Goiter - gland enlarges in an effort to increase function.
What is myxedema?
Unique characteristic finding of hypothyroidism. Protein-carb complexes accumulate in the extracellular matrix, drawing water into the tissues >> boggy, nonpitting, edematous tissues, esp on face, mucous membranes, hands & feet.
What are the diagnostic criteria of hypothyroidism?
Labs - TSH, free T4, T3 & T4 uptake, thyroid autoantibodies, antithyroglobulin.
How is hypothyroidism treated?
Lifelong replacement therapy.
What is Cushing syndrome?
A condition of excess glucocorticoids secreted from the adrenal cortex.
What do glucocorticoids contribute to?
Metabolic function, inflammatory/immune resonses, stress response.
What are the causes of Cushing syndrome?
1. Long-term administration of exogenous glucocorticoids
2. Tumors of pituitary, adrenals, or distant sites (ectopic hormones secreted)
What are the clinical manifestations of Cushing syndrome?
Metabolic alterations; obesity of trunk, face "moon face", and upper back "buffalo hump"
Suppression of inflammation or immunity
Impaired stress response
What are the diagnostic criteria for Cushing syndrome?
Cortisol levels in 24-hour urine
Imaging studies to detect tumors.
How is Cushing syndrome treated?
Remove excess cortisol secretion
Taper exogenous glucocorticoid meds
Surgically remove tumors, or chemo or radiation.
What is Addison Disease?
Autoimmune destruction of the adrenal cortex. Adrenal gland can't produce glucocorticoids, mineralcorticoids or androgens. Results in increased ACTH levels (trying to stimulate secretion of these hormones)
What are the manifestations of Addison disease?
Darker skin pigmentation (high ACTH)
Glucocorticoid deficiency > hypoglycemia, weakness, poor stress response, fatigue, anorexia, n/v, weight loss, personality changes.
Mineralcorticoid deficiency > dehydration, hyponatremia, hyperkalemia, hypotension, weakness, fatigue, shock
What are the diagnostic criteria of Addison disease?
Serum corticosteroid levels that remain depressed even after administration of ACTH.
What are the 3 categories of hormones?
1. Protein - large molecules; bind to receptors present on outside of target cells
2. Steroid - cholesterol based & lipid soluble; cross cell membrane & bind to receptors inside cell
3. Amino acid - bound to carrier proteins; bind to cell membrane, activate a second messenger.
How are hormones transported?
Either free/unbound or attached to a transport carrier.
Unbound: Peptide & protein hormones
Carried by protein: steroid & thyroid hormones. Synthesized in liver.
T/F: drugs that compete with the hormonal binding element will increase hormone activity.
Ex - ASA competes w/ thyroid hormone for binding sites. A pt w/ hyperthyroid will increase T3 level if given ASA.
What is the brain of the brain called?
Where does the hypothalamus receive info from?
The CNS & PNS.
What statuses does the hypothalamus regulate?
T/F: The hypothalamus gets input from most of the other body hormones.
T/F: In the hypothalamic-pituitary system, ultimate determination of whether a hormone gets released is under the control of the pituitary.
False: the hypothalamus.
What are 4 releasing hormones?
1. Growth hormone releasing hormone (GHRH)
2. Thyrotropin releasing hormone (TRH)
3. Corticotropin releasing hormone (CRH)
4. Gonadotropin releasing hormone (GnRH)
What does FSH and LH stimulate?
What does TSH stimulate?
What does ACTH stimulate?
What controls GH release?
What stimulates GH secretion? What inhibits it?
Stimulates: hypoglycemia, fasting, starvation, stress. GHRH.
Inhibits: elevated glucose levels, free fatty acid release, obesity, cortisol. Somatostatin.
What hormones act on the posterior pituitary?
Volcy: ADH, oxytocin
What regulates pituitary hormone secretion?
Level of circulating hormone produced by the target gland.
Cells in the hypothalamus keep tabs on these levels.
The hypothalamus makes _____ _____ which are sent to the _____ pituitary, which then releases _____ hormones into systemic circulation
Releasing hormones; anterior; tropic
Releasing hormones come from the _____ and trophic hormones come from the _______.
The ____ and the ____ act as sensors that are constantly gauging levels of hormones in the body.
T/F: both T3 and T4 exert positive feedback on the hypothalamus.
False; both exert negative feedback.
Where is T4 converted to T3?
In the body tissues. It's inactive until it gets converted.
T3 stimulates ________.
T3 and T4 are both carried by ________.
T/F: the target cells of thyroid hormone are almost all the cells of the body.
How does thyroid hormone stimulate the metabolic rate of its target cells?
Increases the metabolism of protein, fat & carbs
If the primary effect of thyroid hormone is to stimulate metabolic rate, what is the secondary effect?
Stimulate the rate of the sodium-potassium pump in the target cells. Both functions increase energy utilization of cells >> thus increasing basic metabolic rate (BMR), burning kcals & increasing heat production.
_____ hormone is essential for normal growth & development of all body cells AND is required for the function of growth hormone.
What does increased responsiveness of target cells to catecholamines (that thyroid hormone is responsible for) induce?
Increased heart rate, emotional responsiveness, rate of depolarization of skeletal muscle (thus, + speed of skeletal muscle contractions)
What are the 3 types of hormone disorders?
Primary - abnormality in the gland; Secondary - abnormality in stimulation from the pituitary; Tertiary - abnormality in stimulation from the hypothalamus.
In panhypopituitarism the ____ lobe fails to secret all hormones.
What is a deficiency of growth hormone that causes retarded growth & development?
What are 3 pituitary gland disorders?
Panhypopituitarism, pituitary dwarfism, diabetes insipidus
According to Volcy, what causes diabetes inspidus?
A pituitary tumor
What are all of the HPA secretion & feedback mechanisms?
____ reactions use energy to build/synthesize. ___ reactions break down substances to release energy.
____, and ____ aid in anabolism.
Insulin, anabolic steroids
____, ____ and ____ aid in catabolism
Glucagon, epinephrine, cortisol
What are the 3 major adrenal cortical hormones?
Cortisol, testosterone, aldosterone
What are the 3 main actions of cortisol?
1. + plasma proteins; 2. -immune/inflammatory systems; 3. +catabolism (muscle breakdown, +free fatty acids, +blood glucose, +SNS response)
What hormone disorder can cause visual disturbances from tumor encroachment in optic chiasm?
Growth hormone overproduction resulting from pituitary adenoma.
What can cause prolactin overproduction? What does it cause?
Small pituitary adenoma or other conditions that affect the function of the hypothalamus. It results in amenorrhea and galactorrhea (milk secretion from non-pregnant breasts)
How does GH lead to increased circulating blood glucose?
Insensitivity to insulin; cells don't carry glucose intracellularly
Cardiac hypertrophy, hypertension, and diabetes mellitus are common complications of ___________
What is a functional vs. non-functional pituitary tumor?
Functional tumors produce hormones that cause clinical manifestations; non-functional tumors don't produce hormones, but exert other effects.
Overproduction of ____ results in glucose intolerance.
How are is altered hormone function most commonly manifested?
Altered growth, reproductive function or metabolism/energy level
How is altered hormone function detected?
H&P, labs (serum & urine), imaging studies, genetic testing
How does SIADH contribute to altered cell function?
Promotes excessive water retention in the cell, which alters function.
If a pt has low T3 levels, high TSH levels and normal TRH levels, where is the problem?
The cause of _____ is unknown
T/F: hypothyroidism can only be acquired.
False; it's acquired or congenital.
What 3 things can hypothyroidism result from?
Deficient synthesis of TH; destruction of thyroid gland; impaired secretion of TSH or TRH.
What are 4 common causes of hypothyroidism?
Autoimmunity, genetic defects, injury to gland, iodine deficiency.