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The nervous system controls body functions via ___________, while the endocrine system uses chemical messengers called ___________.
- Impulses and neurotransmitters
- Endocrine hormones
What are examples of neurotransmitters that are also known as neurohormones?
- Vasopressin (ADH)
What is the speed and duration of the effects of endocrine action as compared to that of nervous system action?
- Action is relatively slower.
- Duration is longer.
In endocrine action, the hormone is distributed in blood and binds to ______ target cells.
Growth hormone (GH) secreted by the anterior pituitary gland binding to receptors on bone stimulating growth in children is an example of what kind of action?
In paracrine action, the hormone acts _______ by diffusing from its source to target cells in the ________.
Somatostatin secreted from pancreatic delta cells that inhibit glucagon secretion from pancreatic alpha cells is an example of what kind of action?
In autocrine action, the hormone acts on the _________ that produced it.
Interleukin 2 stimulating the cell that secreted it to proliferate is an example of what kind of action?
What are the three hormone interactions?
- Permissive effect
- Antagonistic effect
- Synergistic effect
In permissive effect, the action of one hormone on a target cell requires a _____ or _______ exposure to a second hormone. In this situation, the ___________ is said to have a permission effect on the __________.
- Second hormone
- First hormone
Epinephrine alone weakly stimulates lipolysis, but when a small quantity of thyroid hormones (T3, T4) are present, epinephrine strongly stimulates lipolysis. What effect is this an example of?
In antagonistic effect, one hormone ______ the action(s) or another hormone.
What is an example of hormones that have an antagonistic effect on each other?
Glucagon and insulin
In synergistic effect, the effect of two hormones acting together is _______ than the effect of each hormone acting alone.
What is an example of hormones that are synergistic to each other?
Estrogen and FSH (stimulate development of oocytes)
_________ involves receptors located on or in target cells that bind hormone.
Circulating hormones are slowly inactivated by the ______ and/or excreted by the ______.
How long do circulating hormones remain in the system? What may cause excess levels to accumulate?
- Minutes to a few hours.
- Kidney or liver function impaired.
What are the three factors that determine the responsiveness of a target cell to a hormone?
- Hormone concentration
- Number of available receptors
- Presence of other hormones
What are the chemical classes of hormones?
Which lipid-soluble hormones are synthesized by the adrenal glands, kidneys, gonads, and contain a four-ring structure synthesized from cholesterol? What are some examples?
- Steroid hormones
- Estrogen, testosterone, cortisol
Which lipid-soluble hormones are synthesized by attachment of iodine to tyrosine?
- Thyroid hormones T3 and T4
- (tyrosine is already lipid soluble but iodination enhances this feature)
Which lipid soluble hormone is synthesized in vascular endothelial cells and neurons, and acts as both a hormone and neurotransmitter?
Name the amines and their derivatives that make up some water soluble hormones.
- Catecholamines (epinephrine, norepinephrine)
- Serotonin and melatonin
Name the peptide water soluble hormones.
- Human growth hormone (hGH)
How are water soluble hormone transported in the body?
In their free (unbound) form in blood.
How are lipid soluble hormones transported in the body?
90-99.9% are transported bound to plasma (transport) proteins (ie. thyroxine-binding globulin).
Lipid soluble hormones bound to plasma proteins are more _________ and easier to transport in blood. These hormones are slowly excreted by the _______.
Lipid soluble hormones, by virute of their mode of transportation, provide a _________.
How do lipid soluble hormones provide a hormone reserve?
As hormone dissociates from its carrier protein, leaves the blood and binds to a target cell, other transport proteins release new free hormone into the blood to replace what was lost.
Why is synthetic thyroid hormone able to be taken orally, while insulin must be injected subcutaneously?
- Synthetic thyroid hormone is lipid soluble and is easily absorbed through the intestinal wall.
- Insulin is water soluble and would be destroyed by digestive enzymes.
Receptors for lipid soluble hormones are located _______ target cells.
Receptors for water soluble hormones are part of the ___________ of target cells.
Plasma membrane (a portion of the protein molecule is exposed on the cell surface).
What term refers to the number of receptors decreasing when a hormone concentration in plasma increases?
Down-regulation (target cell becomes LESS receptive to hormone)
What term refers to the number of receptors increasing when a hormone concentration in plasma decreases?
Up-regulation (target cell becomes MORE receptive to hormone)
What is the mode of action (MOA) for lipid soluble hormones?
They diffuse through cell membranes and combine with intracellular receptors within the cytosol or nucleus causing biochemical/physiologic changes in target cell (alteration of gene expression via synthesis of new mRNA & new proteins).
What is the mode of action (MOA) for water soluble hormones?
- Cannot diffuse through lipid bilayer of cell membranes so they must be "assisted".
- They bind to transmembrane receptors protruding from the cell surface.
- Once the hormone binds it acts as a first messenger.
- This action produces a second messenger (intracellular mediator) inside the cell which produces a cellular response.
A water soluble hormone's action is normally adequate even when the plasma concentration is ____; a single hormone's molecule's effect may be amplified several million-fold due to its initiation of a _________ inside the cell.
What is the most common second messenger for water soluble hormones? Where is it synthesized?
- Cyclic AMP (cAMP)
- Synthesized in the cytosol from ATP via adenylate cyclase found on the inner aspect of a cell membrane.
Name the hormone effects for antidiuretic hormone (ADH), aldosterone, thyroid hormone, catecholamines, anterior pituitary hormones, and thymic hormones.
- ADH: fluid homeostasis
- Aldosterone: electrolyte balance
- Thyroid hormone: temperature regulation, energy balance
- Catecholamines: muscle activity (smooth and cardiac)
- Ant. pituitary hormones: glandular secretion
- Thymic hormones: immune responses
Name the hormones that have effects on growth and development.
- Thyroid hormones
- Sex/anabolic hormones
Name the hormones that have effects on reproductive processes.
Name the hormones that have effects on homeostatic maintenance of cardiac output and BP during stress.
- Angiotensin II
What is the primary homeostatic mechanism within the endocrine system?
Negative feedback (hormones released in short bursts when needed)
A ____ plasma concentration of a _________ stimulates one or more endocrine organs to secrete ____________ in order to ________ the concentration of the _________.
- Circulating hormone
- Activating hormones
- Circulating hormone
- (end result of negative feedback in this case is increased secretion of the circulating hormone/plasma concentration increases)
In negative feedback control of hormone synthesis and secretion, once optimal concentration of previously low ___________ is reached, further secretion of ____________ is _________ until the cycle repeats itself.
- Circulating hormone
- Activating hormone
Positive feedback _______ a hormone's effect(s).
Amplifies (original stimulus is promoted rather than negated; ie. labor)
Simulatory input from the sympathetic nervous system on the adrenal medulla causing epinephrine and norepinephrine secretion is an example of what control factor?
Blood Ca++ concentration regulating parathyroid hormone (PTH) release from the parathyroid glands is an example of what control factor?
What is the overall function of the hypothalamus? Is it a separate organ?
- Controls ANS and is the major link between the nervous system and the endocrine system.
- Is not a separate organ (part of the thalamus).
What does the hypthalamus regulate?
- Sexual behavior
- With pituitary regulates growth, development, metabolism, overall homeostasis.
Where does the hypothalamus receive input from?
- Cerebral cortex, limbic system
- Internal organs and retina (sensory)
Hypothalamic hormones that act on the anterior pituitary gland are synthesized in _________________ near the median eminence and above the optic chiasm.
hypothalamic neurosecretory cells
Hypothalamic hormones that act on the anterior pituitary gland are packaged in ___________ then transported by axons to axon terminals near the superior aspect of the ___________.
- secretory vesicles
Nerve impulses stimulate release of hypothalamic hormones that act on the anterior pituitary gland from axon terminals via _________ from the secretory vesicles.
Hypothalamic hormones that act on the anterior pituitary gland that have been released from axon terminals diffuse into the ______________ (supplied by the superior hypophyseal artery).
primary capillary plexus
Hypothalamic hormones that act on the anterior pituitary gland that have diffused into the primary capillary plexus are then transported by the hypophyseal portal veins to the _____________ of the of hypophyseal portal system (adjacent to anterior pituitary).
secondary capillary plexus
Hypothalamic hormones that act on the anterior pituitary gland that are in the secondary capillary plexus then diffuse into ___________ where they exert their action.
anterior pituitary target cells
Name the hormones that stimulate release of anterior pituitary hormones (hypothalamic releasing hormones).
- GHRH: growth hormone releasing hormone
- TRH: thyrotropin releasing hormone
- CRH: corticotropin releasing hormone
- GnRH: gonadotropin releasing hormone
- PRH: prolactin releasing hormone
Name the hormones that inhibit release of anterior pituitary hormones (hypothalamic inhibiting hormones).
- GHIH: growth hormone inhibiting hormone
- PIH: prolactin inhibiting hormone (AKA dopamine)
Name other hypothalamic hormones other than releasing and inhibiting anterior pituitary hormones.
- Anti-diuretic hormone (ADH): synthesized in neuron cell bodies in supraoptic nuclei
- Oxytocin: synthesized within neuron cell bodies in paraventricular nuclei
Where are anti-diuretic hormone (ADH) and oxytocin transported to and stored? How are they released?
- Posterior pituitary gland.
- Released as needed via neuroendocrine reflexes.
ADH and oxytocin from the posterior pituitary gland are packaged in _________ that move from the supraoptic and paraventricular nuclei down to _________ located within the posterior pituitary gland.
- Secretory vesicles
- Axon terminals
Where do the posterior pituitary gland hormones linger until a nerve impulse triggers their release? How are they released?
- Axon terminals
- Exocytosis from secretory vesicles
The released hormones of the posterior pituitary gland diffuse into the _______________ then are transported away from the posterior pituitary gland to the general blood circulation via the ______________.
- Capillary plexus of the infundibular process
- Posterior hypophyseal veins
Where is the pituitary gland located? How is it connected to the hypothalamus?
- Within the sella turcica of the sphenoid bone.
- Via a stalk called the infundibulum.
What percentage of the pituitary gland is made up by the anterior segment? What is it also known as?
- About 75% of total weight.
- AKA adenohypophysis
What are the 2 components of the anterior pituitary gland?
- Pars distalis: glandular tissue (largest portion)
- Pars tuberalis: covers infundibulum (sheath like)
The anterior pituitary gland produces ___________ from specific cell types with the gland.
Tropic hormones (each exerts its effect on another endocrine gland)
Once anterior pituitary hormones synthesized and released, they pass into the ___________.
secondary capillary plexus
Anterior pituitary hormones in the secondary capillary plexus are transported via the _____________ to the general circulation.
anterior hypophyseal veins
Which anterior pituitary tropic hormone is produced by somatotrophs?
Human growth hormone (hGH)
Which anterior pituitary tropic hormone is produced by lactotrophs?
Which anterior pituitary tropic hormones are produced by corticotrophs?
- Adrenocorticotropic hormone (ACTH)
- Melanocyte-stimulating hormone (MSH)
Which anterior pituitary tropic hormone is produced by thyrotrophs?
Thyroid-stimulating hormone (TSH)
Which anterior pituitary tropic hormones are produced by gonadotrophs?
- Follicle-stimulating hormone (FSH)
- Luteinizing hormone (LH)
Negative feedback from hormones produced by target glands _______ anterior pituitary hormone secretion _______ and _______ secretion of of hypothalamic releasing hormones.
Most hGH effects are indirect via stimulation of _________________ produced in liver, bone, muscle and cartilage.
insulin-like growth factors (IGFs)
What does IGF stimulate in children and adults?
- Child: growth (bone, cartilage, muscle)
- Adult: tissue maintenance, healing, repair
What are the metabolic effects of hGH?
- Increases protein synthesis
- Decreases protein catabolism
- Above result in increased plasma protein concentration
- Increases breakdown of triglycerides
- Decreases glucose uptake by tissue cells, increases lever glycogenolysis (increased plasma glucose concentration)
What is the major regulator of hGH secretion?
Blood glucose concentration
Low blood glucose ______ GHRH secretion and _______ GHIH secretion.
- (hGH secretion increases therefore increasing glucose concentration/high blood glucose has opposite effect)
What are the neural factors that help control hGH secretion?
- Sympathetic nervous system stimulation (stress, strenuous exercise)
- Deep, non-REM sleep
- Both these factors stimulate hGH secretion.
HGH secretion increases under the of which hormones?
HGH secretion decreases when plasma levels of what hormones are low?
T3 and T4
What is the most common etiology for hGH hypersecretion?
Benign pituitary adenoma
What condition is described by hGH hypersecretion in childhood stimulates chondrogenesis in epiphyseal plates resulting in a very tall individual with almost normal body proportions?
Giantism (Gigantism) (childhood hGH hypersecretion)
What condition is described as hGH hypersecretion in adulthood, causing enlargement of internal organs, thickened skin, and bone thickening (enlarged facial features, feet and fingers)?
What can chronically elevated plasma hGH cause?
Pituitary diabetes (pancreatic cells "burn out")
What condition is described as hGH hyposecretion in childhood, causing epiphyseal plates to close before normal height is attained plus the individual retaining childlike features?
What is congenital dwarfism?
Due to a genetic IGF deficiency.
HGH secretion ________ as we age which may cause muscle wasting and fat deposition.
Which hormone controls synthesis and secretion of cortisol and other adrenocorticoids from the adrenal cortex?
ACTH (adrenocorticotropic hormone)
Cortisol secreted from the adrenal cortex exerts ___________ on CRH secretion from the hypothalamus and _____ secretion from the anterior pituitary gland.
What hormone intiates milk synthesis and secretion if the mammary glands are prepared during pregnancy?
What are the hormones that provide permissive action to prolactin to initiate milk synthesis and secretion?
How is the secretion of prolactin (PRL) controlled?
- Prolactin-releasing hormone (PRH)
- Prolactin-inhibiting hormone (PIH) (AKA dopamine)
Dopamine (PIH) produced in the hypothalamus inhibits prolactin secretion in which individuals? Why?
- Normal, non-nursing individuals.
- Because prolactin is secreted continuously unless otherwise inhibited.
Low levels of estrogen and progesterone just prior to menstruation ______ secretion of PIH (dopamine).
Inhibits (stimulating prolactin secretion which probably accounts for breast tenderness)
During the rest of the female cycle once menstruation begins, estrogen secretion ________, PIH (dopamine) secretion ________ and prolactin secretion is _______.
What is the act of nursing believed to do in relation to PIH (dopamine) and prolactin secretion?
It is believed nursing inhibits PIH secretion and stimulates prolactin secretion.
What is the most common cause of prolactin (PRL) hypersecretion? When would you consider this diagnosis?
- Prolactinoma (benign pituitary adenoma)
- Consider this if a non-pregnant, non-lactating female complains of milky breast discharge.
What does decreased circulating plasma estrogen or testosterone concentration stimulate secretion of from the hypothalamus?
GnRH (gonadotropin releasing hormone)
Gonadotropin releasing hormone (GnRH) stimulates secretion of what two sex hormones from the anterior pituitary?
What is the posterior pituitary gland also known as, and what are it's two components?
- AKA neurohypophysis
- 2 parts are: Pars nervosa (bulbar portion), and Infundibulum (stalk)
Where is antidiuretic hormone (ADH) synthesized and stored? What is another name for this hormone?
- Synthesized in the hypothalamus, stored (and secreted) by the posterior pituitary gland.
- AKA vasopressin
The quantity of antidiuretic hormone (ADH) secreted depends on what two factors?
- Blood volume
- Blood osmotic pressure
How does the blood osmotic pressure influence secretion of ADH?
High blood colloid osmotic pressure stimulates osmoreceptors in the hypothalamus which increases synthesis and packaging of ADH into vesicles for transport to the posterior pituitary.
When ADH is release from the __________, it is carried throughout the body via the _________.
- Posterior pituitary gland
What is the action of ADH at it's target tissues?
- Kidneys: increased water reabsorption by tubules
- Sudoriferous (sweat) glands: decreased sweating
- Vascular smooth muscle: arteriolar constriction during significant hemorrhage
What is the effect on ADH secretion by sensory impulses from atrial receptors in response to increased blood volume?
Secretion is inhibited by atrial antriuretic peptide (ANP) released in response to high blood pressure which reduces water load in the circulatory system to compensate.
What is the cause of diabetes insipidous?
Deficiency of circulating ADH
What is the usual cause of diabetes insipidous?
- Trauma to the infundibulum.
- AKA neurogenic or central DI
What is the cause of nephrogenic diabetes insipidous?
ADH receptor defect: renal ADH receptors don't recognize ADH
What are the symptoms of diabetes insipidus (DI)?
What is the hormone that stimulates milk ejection or "let down"? What else does this hormone do?
- Stimulates uterine contractions during labor (and during nursing to expel placenta).
What is the neuro-endocrine reflex stimulated by the action of a nursing infant?
Which gland is butterfly-like, 20-25 grams in size and is the largest of the "pure" endocrine glands?
Describe the location of the thyroid.
- Later lobes (wings) on each side of the trachea project upward to just below the larynx.
- Lobes are connected by an isthmus located anterior to the trachea.
What hormone do the parafollicular cells of the thyroid synthesis?
Describe the blood flow to the thyroid gland.
Extensive blood flow (20-120 ml/min)
What part of the thyroid gland is described as microscopic, spherical sacs? How are they arranged?
- Single layer of follicular cells surrounding a cavity.
What does the cavity of a thyroid follicle contain? What is the primary protein?
- Protein-rich fluid known as colloid.
What are the hormones that the follicles of the thyroid synthesize?
- Thyroxine (T4): principle thyroid hormone
- Triiodothyronine (T3): very small amount synthesized and released (most T3 is synthesized in cells of target organs)
Thyroid follicles actively accumulate _______ from blood and secrete it into the colloid. Within follicles, it is oxidized to ______.
What is iodine attached to?
Tyrosine (amino acid within thyroglobulin)
One iodine + tyrosine =?
Two iodine + tyrosine =?
- Monoiodotyrosine (MIT)
- Diiodotyrosine (DIT)
What modifies the structure of MIT and DIT?
Enzymes within the colloid
What hormones are formed by combining MIT and DIT?
- One MIT + one DIT = triiodothyronine (T3)
- One DIT + one DIT = thyroxine (T4)
- (T3 and T4 remain attached to thyroglobulin w/in the colloid)
How is thyroid hormone synthesized and secreted upon being stimulated by thyroid-stimulating hormone (TSH)?
- Follicle cells take up small amount of colloid via pinocytosis.
- T3 and T4 are hydrolyzed from thyroglobulin and secreted as free hormone into the blood.
- Thyroglobulin remains within the colloid.
More than 99% of T4 and T3 produced in the thyroid gland binds to __________ almost immediately, then it circulates throughout the body. Which of these hormones is secreted in greatest quantity?
- thyroxine-binding globulin
What is the active form of thyroid hormone?
What hormone from the hypothalamus stimulates TSH secretion from the anterior pituitary gland?
TRH (thyroid releasing hormone)
What actions occur within the thyroid gland?
- Thyroid hormone synthesis/secretion
- Follicular cell growth
Circulating T3 and T4 exerts ___________ control on further thyroid hormone synthesis/secretion.
Negative feedback (secretion of TRH and TSH decreases)
What stimulates increased secretion of TRH and TSH?
- Low basal metabolic rate (BMR)
- Exposure to cold climate
What is the approximate supply of thyroid hormone that is stored in the colloid of thyroid follicular cells?
2-3 month supply
What are the activities of thyroid hormone?
- Regulation of metabolic rate and heat production (thyroid hormone increases BMR and O2 consumption at rest for ATP production).
- Stimulates Na/K pumps (use large amount of ATP).
- Calorigenic effects (related to increased ATP use for thermoregulation-survival in cold climate).
- Increased protein synthesis for ATP production.
- Increased cellular uptake of glucose for ATP production.
- Increased lipolysis for ATP production (stimulates excretion of cholesterol in bile).
- Up-regulation of beta adrenergic receptors (enhances action of epinephrine on the heart, increases neuronal activity causing nervousness/tremor).
- Stimulates maturation and development of the nervous system.
- Stimulates body growth by increasing protein synthesis and hGH synthesis and secretion.
What are the etiologies for hypothyroidism?
- Inadequate thyroid hormone synthesis and secretion from thyroid gland.
- Inadequate secretion of TSH from anterior pituitary.
What are the characteristics of myxedema (severe adult hypothyroidism)?
- Edema of facial tissues
- Decreased HR
- Cold intolerance
- Dry hair and skin
- Muscle weakness
- Obesity (uncommon)
What is the cause for endemic goiter?
- Dietary iodine deficiency.
- Inability to utilize iodide.
Lack of negative feedback results in ________ pituitary TSH secretion, stimulating growth of thyroid follicles.
Increased (size of thyroid gland increases significantly)
What is an autoimmune disorder caused by production of thyroid-stimulating immunoglobulin that mimics TSH at TSH receptors, overstimulating the thyroid gland?
What are the clinical signs of Grave's disease?
- Enlarged thyroid (toxic goiter)
- Exophthalmos (caused by retro-orbital edema, not painful)
What are the symptoms and clinical signs of hyperthyroidism?
- Heat intolerance
- Excessive sweating
- Weight loss
- Muscle weakness
- Extreme fatigue w/ occasional inability to sleep
- Elevated heart rate (tachycardia)
- Hand tremor
What are the important roles of blood Ca++?
- Nerve impulse initiation, propagation, synaptic vesicle release.
- Muscle action potentials.
- Blood coagulation.
What are the three factors bone breakdown depend on?
- Ratio of osteoblast to osteoclast activity.
- Intestinal absorption of calcium and phosphate.
- Urinary excretion of calcium and phosphate.
Parathyroid hormone (PTH) ________ blood Ca++ and ________ blood phosphate.
Calcitonin ________ blood Ca++ and phosphate.
Calcitriol ________ blood Ca++ and phosphate.
What are the four small glands partially imbedded in the posterior surface of the thyroid gland? What is the principle cell of these glands also called and what do they secrete?
- Parathyroid glands
- AKA Chief cells
- Secrete PTH
What are the three processes with which PTH increases blood Ca++ levels?
- Increases osteoclast activity.
- Increases renal tubular reabsorption of Ca++ and Mg++
- Stimulates renal synthesis of calcitriol which increases intestinal absorption of Ca++, phosphate, and Mg++
Blood PTH level _______ in response to a ________ level of plasma Ca++ concentration (and vice versa).
What are the normal levels of total plasma Ca++ and normal ionized (free) plasma Ca++?
- Normal total: 9.0-10.5 mg/dL
- Normal ionized: 4.7-5.3 mg/dL
What hormone is produced by the parafollicular (C cells) of the thyroid gland?
How does calcitonin decrease plasma Ca++ and phosphate?
- Inhibits formation and activity of osteoclasts.
- Decreases renal tubular Ca++ reabsorption.
What is required for children to have normal bone formation?
How does the limited physiological role of calcitonin in the adult benefit an individual who has had a total thyroidectomy/the source of calcitonin is removed?
Hypercalcemia does not occur due to a compensatory decrease in PTH secretion.
How is calcitonin secretion controlled/regulated?
- By plasma Ca++ levels.
- **Increases significantly with small increase of Ca++
- **Decreases rapidly when plasma Ca++ decreases
What is the active form of vitamin D? What does it do?
- Calcitriol (1,25 dihydroxycholecalciferol)
- Increases plasma Ca++, phosphate and Mg++
Where is vitamin D converted to its active form?
Liver and kidneys
In vivo formation of calcitriol involves conversion of __________ to __________ in the skin (via UV exposure), followed by liver hydroxylation to _____________, and hydoxylation to the active form in ____________.
- Kidney (this step requires PTH)
What is the primary hormonal effect of calcitriol activity?
Increases intestinal absorption of Ca++, phosphate, Mg++ by stimulating production of calcium biding protein in intestinal epithelial cells at the brush border.
What are the signs and symptoms of hypoparathyroidism (PTH deficiency)?
- Muscle spasms, twitches, and/or tetany
- Possible death if not recognized early
What is the treatment for hypoparathyroidism (PTH deficiency)?
High-dose vitamin D, increased dietary Ca++ intake
How does a parathyroidectomy affect plasma Ca++?
Decreases plasma Ca++ (muscle tetany may occur)
In hypoparathyroidism (PTH deficiency), what happens with the Na+ channels of membranes? What can happen if Ca++ is not given to the patient?
- Na+ channels open even there is very little increase in membrane potential.
- Laryngospasm and death may occur unless Ca++ is given.
What are the signs and symptoms of hyperparathyroidism (increased PTH)?
- Decalcified, weakened, easily-fractured bone.
- Increased risk of kidney stones due to high concentration of calcium and phosphate in urine.
What condition is a result of a long-term childhood dietary vitamin D deficiency causing persistently low plasma Ca++ concentration?
- PTH secretion is significantly increased, parathyroid gland hypertrophy occurs.
What are the signs and symptoms of rickets and how is it treated?
- Bones are soft (demineralized) and deformed.
- Treated with vitamin D, increased dietary Ca++ and phosphate intake.
What is a condition in which bone demineralization and softening occurs due to adult vitamin D deficiency?
Osteomalacia (seldom due to isolated low dietary vitamin D intake)
What are the etiologies of osteomalacia?
- Celiac disease (intestinal malabsorption disorders)
- Inadequate exposure to sunlight
- Renal disease
What condition is described as decreased bone mass, primarily due to loss of organic matrix? What risk increases as a result of this?
- Increases risk of fractures
What are the etiologies of osteoporosis?
- Old age
- Estrogen deficiency (menopause) and testosterone deficiency (in men)
- Lack of exercise, decreased ambulation
- Cushing's syndrome
What is the chance in post-menopausal women as compared to men to develop osteoporosis?
10X higher incidence (main goal is prevention!)
What is the treatment for osteoporosis prevention/reduced progression?
- Ca++ rich diet or supplements
- Weight bearing exercise
What is the condition in which bone demineralization is caused by abnormally increased osteoclast activity? What is the treatment?
- Paget's disease of the bone
- Treated with very large doses of calcitonin
Flattened, pyramidal-shaped glands located superior and adjacent to the kidneys, highly vascular, covered by a capsule.
What is the composition of the adrenal glands?
- Large outer cortex
- Small inner medulla derived from neural crest ectoderm (gives rise to specialized sympathetic ganglia cells called chromaffin cells)
What are the zones of the adrenal cortex?
- 1) zona glomerulosa: produces mineralocorticoids (primarily aldosterone)
- 2) zona fasiculata: largest middle layer, produces glucocorticoids (primarily cortisol)
- 3) zona reticularis: produces small amounts of gonadocorticoids (primarily DHEA), also produces androstenedione, some glucocorticoids, and small amount of estrogen
95% of mineralocorticoid activity in the body is due to ___________.
What does aldosterone do in the body?
- Regulates Na+ and K+ ion homeostasis by increasing renal tubular reabsorption of Na+ (for ECF), and increasing renal tubular epithelial cell secretion of K+.
- Promotes excretion of H+ in urine.
What stimulates secretion of aldosterone by the adrenal cortex?
- Angiotensin II (assists in maintaining/increasing BP by increasing renal reabsorption of Na+)
- Increased plasma K+ concentration also stimulates aldosterone secretion
How is hyperaldosteronsim (Conn's Disease) manifested and what are the signs and symptoms?
- Manifested by hypokalemia.
- Signs and symptoms: severe muscle weakness/paralysis, depressed SA and AV node conduction, hypertension (hypernatremia)
What are the glucocorticoids?
- Cortisol (most abundant, 95% of activity)
What are the effects of cortisol?
- Increases protein catabolism primarily in muscle.
- Stimulates gluconeogenesis from lactate and amino acids increasing blood glucose.
- Stimulates lipolysis.
- Increases resistance to stress (exercise, fasting, fright, etc) by increasing blood glucose and BP.
- Possesses anti-inflammatory properties (decreases mast cell activity, used clinically for treatment of chronic inflammation).
- Immunosuppression (high doses used to prevent transplant rejection).
What are the adverse effects of excess glucocorticoids?
- Decreases connective tissue repair needed for wound healing.
- Decreases resistance to infection (immunosuppression).
- Increases risk for osteopenia or osteoporosis (protein catabolism causes loss of organic bone matrix).
- Possible mental disturbances.
Control of cortisol secretion is accomplished via _____________ to the hypothalamus and pituitary.
What does a decreased circulating level of cortisol stimulate (in sequence)?
- CRH secretion (hypothalamus)
- ACTH secretion (anterior pituitary)
- Cortisol secretion
What can override negative feedback regulation for CRH secretion?
What condition is a result of cortisol and aldosterone hyposecretion?
Addison's Disease (AKA primary adrenocorticoid insufficiency)
What are the etiologies of Addison's disease?
- 1: autoimmune process that that causes adrenal atrophy (most common)
- 2: ACTH receptor blockade
- 3: infection (ie., tuberculosis)
What are the signs and symptoms of decreased cortisol secretion (Addison's disease)?
- Hypoglycemia between meals
- Weight loss
- Muscle weakness
- Inability to resist stress
What are the signs and symptoms of decreased aldosterone secretion (Addison's disease)?
- Hyperkalemia and hyponatremia
- Hypovolemia (dehydration)
- Metabolic acidosis (increased H+ and K+)
- Decreased CO leading to circulatory shock and death (within 2 weeks w/out treatment)
What are the signs and symptoms of increased ACTH secretion (Addison's disease)?
- Skin bronzing/hyperpigmented macules on lips and nipples.
- Lack of negative feedback control of ACTH secretion.
- Markedly increased ACTH secretion associated with increased MSH secretion.
What are the etiologies of Cushing's syndrome?
- 1) most common etiology: ACTH hypersecretion due to ACTH producing tumor in the pituitary gland (AKA Cushing's disease) which stimulates the adrenal glands to secrete excess cortisol
- 2) adrenal adenoma: causes cortisol hypersecretion (ACTH level is decreased)
- 3) high doses of exogenous glucorticoids: "we did it"
What are the signs and symptoms of someone with Cushing's syndrome?
- Buffalo hump (back of neck)
- Pendulous abdomen with striae
- Moon face (edema)
- Increased protein catabolism (muscle wasting)
- Hyperglycemia (adrenal diabetes)
- Poor wound healing
- Susceptibility to infection
- Decreased stress resistance
- Mood swings
What kind of therapies would cause a patient to exhibit signs and symptoms of Cushing's syndrome?
Use of glucocorticoid therapy for asthma, post organ transplant, or chronic inflammatory diseases.
A small quantity of weak _________ are secreted from the adrenal cortex.
- (dihydroepiandrosterone/DHEA secretion stimulated by ACTH)
What is the significance of the weak androgens (gonadocorticoids) secreted by the adrenal glands for males and females?
- Males: little to no significance, testosterone effects predominate
- Females: important in females, particularly post menopausal (DHEA is the ONLY estrogen source post-meno and stimulates the sex drive in females)
What do the gonadocorticoids stimulate in pre-pubertal boys and girls?
- Growth spurt
- Axillary & pubic hair growth
What is the adrenal medulla composed of?
Chromaffin cells (specialized postganglionic sympathetic neurons surrounding blood sinuses)
What do the chromaffin cells of the adrenal medulla secrete?
Catecholamines: epinephrine (80%) and norepinephrine (20%), trace amount of dopamine
What does locally increased cortisol secretion from the adrenal cortex activate in chromaffin cells?
Enzymes that convert norepinephrine to epinephrine.
What nerve fibers stimulate the adrenal medulla to release large quantities of epinephrine and norepinephrine into blood?
Sympathetic nerve fibers
What are the effects of epinephrine?
- Greater beta receptor stimulation of the heart (markedly increases CO, moderately increases BP).
- Greatly increased BMR (up to 100% above normal in some).
What are the effects of norepinephrine?
- Less effect on cardiac stimulation.
- Significantly increased vasoconstriction in muscles (increases systemic vascular resistance better than epinephrine).
What is a chromaffin cell tumor that hypersecretes epinephrine and norepinephrine?
Where do pheochromocytomas often occur?
In the adrenal medulla (but can occur anywhere along sympathetic paraganglia).
Presence of a pheo causes a _____________ reaction.
Prolonged "fight or flight" reaction
What are the signs and symptoms of a pheochromocytoma?
- Increased BP (very labile)
- Increased HR
- Elevated BMR
What are para-aortic bodies that are a common location for pheochromocytomas outside the adrenal medulla?
Organs of Zuckerkandl
What cells make up 99% of pancreatic cells, and produce digestive enzymes that perform exocrine function.
What cells make up 1% of pancreatic cells and produce endocrine hormones.
Islets of Langerhans
Which pancreatic cell secretes glucagon? What does it do?
- Alpha (A cells)
- Increases blood glucose.
What pancreatic cell secretes insulin? What does it do?
- Beta (B cells)-compromise about 70% of pancreatic islet cells.
- Decreases blood glucose.
What pancreatic cell secretes somatostatin (same as GHIH)? What does it do?
- Delta (D cells)
- Inhibits glucagon and insulin secretion and GI activity.
What pancreatic cell secretes pancreatic polypeptide? What does it do?
- F cells
- Inhibits somatostatin secretion, pancreatic enzyme secretion, and gallbladder contraction.
What besides increasing blood glucose does glucagon do?
- Stimulates glycogenolysis & gluconeogenesis in liver.
- Stimulates lipolysis & ketogenesis for production of free fatty acids as non-glucose energy sources.
How is secretion of glucagon controlled?
- Circulating levels of glucose and insulin.
- Low glucose: stimulates glucagon secretion
- Insulin: inhibits glucagon
What besides glucose and insulin levels influence secretion of glucagon?
Secretion is also stimulated by increased sympathetic nervous system activity (exercise, stress).
What is the effect of insulin on high blood glucose concentration?
Decreases blood glucose by increasing glucose uptake by muscle, liver and adipose cells (doorman).
What does insulin do besides decrease high blood glucose levels?
- Increases amino acid uptake and protein synthesis by cells.
- Stimulates glycogenesis in liver and muscle.
- Inhibits glycogenolysis and gluconeogenesis.
What happens to excess glucose once glycogen stores are filled?
Liver converts it to fatty acids and transports them to adipose tissue for storage.
In what ways, besides blood glucose levels and circulating glucagon levels, is insulin secretion controlled?
- Parasympathetic vagal stimulation of the pancreas.
- Glucose-dependent insulinotropic peptide (GIP) which is secreted in response to the presence of glucose in the GI tract (GIP and other GI hormones potentiate the effect that elevated blood glucose has on insulin secretion-increases).
What increases insulin secretion indirectly?
Circulating hGH, CRH, ACTH, and cortisol.
What condition presents with elevated plasma glucose (hyperglycemia), and a metabolism similar to a starving person?
- Diabetes mellitus
- They use lipids and protein and energy sources (primarily type I).
What in addition to hyperglycemia are characteristic of diabetes mellitus?
- Hyperlipidemia (hypercholesterolemia)
- Varying degrees of ketonemia
What are the "three Ps" of diabetes?
- Polyuria: osmotic diuresis
- Polydipsia: increased thirst due to dehydration (decrease in ICF and ECF)
- Polyphagia: excess hunger, usually seen in type I diabetics (due to increase protein catabolism and tissue wasting)
What is the cause of diabetes mellitus type I? What is another name for this condition?
- Deficient insulin production by pancreatic beta cells.
- AKA insulin-dependent diabetes mellitus (IDDM)
What is the pathophysiology for diabetes mellitus type I? What is the treatment?
- Pancreatic beta cells degenerate and fail to produce insulin (autoimmune process/viral infection).
- Insulin replacement therapy required.
What are signs and symptoms of diabetes mellitus type I other than hyperglycemia?
- Muscle wasting (protein catabolism)
- Peripheral neuropathy and autonomic nervous system dysfunction
What is the most common form of diabetes? What is another term for it? When does it generally occur?
- Diabetes mellitus type II
- AKA non-insulin dependent diabetes mellitus (NIDDM)
- Adult onset (usually)
What is the cause for diabetes mellitus type II?
- Insulin receptor insensitivity (insulin resistance) at tissue cells:
- Initially insulin secretion is increased but as disease progresses secretion decreases due to beta cell burnout.
What are the risk factors for diabetes mellitus type II? What are the signs and symptoms?
- Risk: obesity, lack of exercise, genetics
- S/S: similar to type I DM except muscle wasting is uncommon
What is the treatment for diabetes mellitus type II?
- Initially: diet, exercise (decreases insulin resistance at tissue cells)
- Little later: drugs that stimulate insulin secretion (sulfonylureas) and/or decrease insulin resistance (metformin)
- Later: patients may eventually require insulin
Hyperinsulinemia is a _______________ by pancreatic beta cells to the insensitivity of target tissue cells to insulin.
What does insulin insensitivity at tissue cells do?
- Impairs carbohydrate utilization and storage in body cells.
- Increases blood glucose concentration.
Development of insulin resistance and impaired glucose metabolism in type II diabetes is usually a ____________ beginning with weight gain.
What has research found to be a possible mechanism for hyperinsulinism and insulin resistance in type II DM?
- There are fewer insulin receptors in obese individuals, especially in skeletal muscle, the liver, and adipose tissue.
- Research also suggests various substances released from adipose tissue impair insulin receptor function.
What condition is described as having excess circulating insulin which causes a hypoglycemic state that over-excites the CNS.
What are the characteristics of insulin overdose?
- Weakness, anxiety, tremors, sweating (due to epinephrine, glucagon, and hGH secretion).
- Disorientation, convulsions, and coma (the brain is deprived of glucose).
What is the treatment for insulin overdose?
What are the characteristics of an insulinoma? When should this diagnosis be considered?
- It is an adenoma of an islet of Langerhans (10-15% are malginant and can metastasize through the body).
- Consider this in person who were previously healthy and present with significant unexplained hypoglycemia.
What are the signs, symptoms, and treatment of an insulinoma?
Similar to those for insulin overdose.
What is the cause of diabetic ketoacidosis (DKA)? What is another term for this condition?
- Caused by an insulin deficiency.
- AKA diabetic coma
Who can be affected by diabetic ketoacidosis? What are the clinical signs of DKA?
- May occur in diabetics who inject insulin or in an undiagnosed diabetic (usually type I).
- Clinical signs include "ketone breath" and hyperventilation (Kussmaul's respirations) due to ketoacidosis.
What levels of glucose are seen in hyperglycemia? What is the cause of ketonemia (elevated serum acetone)?
- >/= 250 mg/dl
- Elevated levels of hGH, catecholamines, and glucagon increase lipolysis from adipose tissue and increase liver ketone production.
What are the typical blood gas values seen in diabetic ketoacidosis?
- pH: <7.3 (7.4)
- pCO2: >45 (35-45)
- PO2: >80
- BE: base deficit (normal is -2 to +2)
- HCO3: <15 mEq/L (22-26)
What is the pineal gland and where is it located? What happens to this gland in adults?
- Part of the epithalamus
- In the roof of the 3rd ventricle
- Normally atrophies in the adult
What does the pineal gland consist of?
Masses of neuroglia (supporting structure for nervous system tissue) and secretory cells.
What are the secretory cells of the pineal gland and what do they synthesize?
- Melatonin (serotonin derivative)
How is melatonin secreted?
In a diurnal rhythm, increasing at night and decreasing during daylight.
How is the control of melatonin secretion influenced by darkness?
Sympathetic postganglionic fibers from the superior cervical ganglion release norepinephrine at synapses in contact with pinealocytes which secrete melatonin, promoting sleepiness.
What is the correlation between insomnia and melatonin? Is melatonin effective therapy for insomnia and are there any adverse effects?
- It is thought melatonin "sets" the biological clock.
- Deficiency may be one cause of insomnia.
- Melatonin therapy has been effective but may inhibit reproductive function.
What could be the cause of seasonal affective disorder (SAD)? What is a useful treatment for SAD?
- Melatonin overproduction
- Full spectrum, very bright light therapy
What is a bi-lobed organ within the medastimun that is located anterior to the aorta and posterior to the manubruim? What is the difference in this organ between adults and children?
- Large in children, atrophies after puberty.
What hormones does the thymus produce? What do the hormones do?
- Thymopoietin I and II
- Thymic humoral factor
- Thymic factor
- **all stimulate T cell differentiation into "killer", "helper", and "suppressor" cells**
How does the thymus contribute to the immune system?
- It produces T cells for cell mediated immunity.
- **lymphocyte precursors from bone marrow become thymocytes and mature into T cells**