Endocrine Flashcards
Negative Feedback
- probably the most important monitoring system to see if we have enough
- can only say we don’t need it anymore; it cannot help an organ that is over producing
Example: Low TSH but high T3 & T4
when we have decreases or increases in both, then we have a problem and we must determine the problem
(possible adenoma or hypothalmic issue)
TRH is the mothership messenger that tells the anterior pituitary which says, OK, we need to send messengers to the thyroid because we don’t have enough, then TSH goes out; TSH is underboss: is is the messenger that goes to the thyroid that ways we need more T3 or T4;
They thyroid is the metabolic gas pedal we have increased metabolic activity, AA, etc with Less, we have let up in the gas pedal
Negative Feedback
Thyroid: They hypothalmus releases thyrotropin releasing hormone TRH. TRH causes the release of TSH (thyrotropin). TSH released from the anterior pituitary targets the thyroid gland and stimulates the release of T4 and some T3. Most of T3 is converted in teh periphery. So when there is low circulating thyroid hormones, we would expect that if the negative feedback loop is working, that there would be a high level of TSH in the blood but a low actual thyroid hormone
Hormone effects:
direct effects
&
permissive effects
hormone regulation
up-regulation
down regulation
Direct Effects
I am releasing a hormone and it is going to have “THIS” activity
-Ex: T4 increases metabolic activity in a lot of things
Perissive effects
Ex: cortisol sensitizes the tissue to epinephrine and norepinephrine
-giving a medication will: more sensitive to
and will make things more potent because of the potentiation of things
UP REGULATION
- low numbers of hormones increase the number of receptors per cell
- Lipid controlling drugs work this way:
if only a little bt, receptors will up regulate because the body needs it
-initially sweep a lot of cholesterol out of the system and the liver freaks out because it needs cholesterol to make bile and hormones, especially gonadal hormones and it aus I ned more cholesterol and I don’thave it; so it upregulates hepatocytes that pull LDL out of the system, and with lipid-controlling meds the liver never catches up so the amount of availability on the system is way down because the lier is pulling it out to create what it needs
Down Regulation
High concentrations decrease the number of receptors
- when there are too many hormones in concentration, we have down regulation to say we don’t need anymore and the hormones float out in circulation
- EX: insulin sensitivity:
whenever there are a loss of hormones floating around, either the upper end or too many, cells begin to say “I don’t need that much” ad they down regulate the receptors and it leaves more of that hormone out in circulation just sitting wround. Because a person is diabetic, he has a very high circulating level of glucose, there is a ton if gluose, there is a ton of insulin and hyperinsulinemia makes the tissues sy”Woah, I don’t need that much”, so the tissues actually become less sensitive to the insulin and glusoce molecule together and they take up less of it which exacerbates the problem; we know that people who have diabetes, their insulin sensitivity is a pajor part of the problem
Hypothyroidism
expected:
High TSH, low T3 and T4
Hyperthyroidism
Low TSH, High T3 and T4
Hypothalmic Pituuitary axis
They Hypothalmic-Pituitary axis is the basis for the neuro-endocrine system. They hypothatmus and the pituitary make up the basis for this system, which includes the feedback mechanisms. When the hypothalmus targets the pituitary with particular releasing factors, it causes the release of others that then target distant organs. When those distant organs relese their hormones, catecholamine and other substances, therei presence in the blood or their actions provide negative feedbck reducing subsequent messengers and secretion. This is the Basis for HPA.
Hypothalmic -Pituitary Axis
reason why many of the decadron-type drugs for 54321
-y giving ehn a glucocorticoid, creating a false negative feedback loop (exogenous); hypothalmus is saying “I have a lot of cortisol in the system, what do I need to send?”
ACTH
They Hypothalmus
Pituitary
and target hormones
AXIS
Goes down in line:
Hypothalmus to pituitary to target hormones
Posterior Pituitary
(neurohpyohysys)
stores and releases oxytocin and ADH
(both produced in they hypothalmus and stored in the posterior pituitary)
Anterior Pituitary
(adenohypophysis)
stores multiple hormones including the trophic hormones
Any hormones labeled trophic or tropic:
targets another endocrin hormone
b endorphins
these hormones form a complex with other substances (they are ligands) to bind with other opiod receptors
b lipotropin
Melanocyte stimulating hormone (MSH)
stimulate the production and release of skin pigments from the melanocytes
FSH
stimulates egg maturation and sperm production. When low in women, it tends to cause amenorrhea. If low in men, loss of facial hair, decreaed libido and erectile dysfunction
Prolactin
(luteotrophic hormone…VERY close to lutotropic)
Doesn’t have a known particular releasing factor, but it does have an inhibiting factor in the hypothalmus (most likely dopamine)
It is presumed that there is a releasing factor, but it hasn’t been isolated. Prolactin is also produced in other tissues in the body. Stiulates lactation and normal sexual function.
Supresses ovaian function
Lutenizing hormone (LH)
Lutotropin
- increases the production and release of teroid hormones. -Surge in women releasing egg at ovulation
- defiency in women may cuse wt gain, heavy period, insomnia, irritibility
low in men-reduced testosterone
Growth Hormone (GH)
(somatotropin)
Bone and muscle growth, release of insulin-like factors from the liver
Adrenocorticotrophic hormone (ACTH)
The “Stress” messenger: stimulated the release of glucocorticoids (cortison which increases protein and CHO metabolism, increes anti-inflammatory factors and causes gluconeogenesis (the reason BS elevated when on steroids) and mineralocorticoid (aldosterone) and causes reabsorption of sodium
Hyper/hypo thyroidism
Primary:
dysfunction or disease of the thyroid gland
Hyper/hypo thyroidism
Thyrotoxicisis aka hyperthyroidism
Graves Disease
Most common cause of hypothyroidism
Pretibial myxedema
- auto-immune driven
- body creates antibodies to thyroid itself; diseases they thyroid and creates an over production of thyroid)
Hyperthyroidism resulting from nodular thyroid disease
Goiter
Secondary
alteration if pituitary TSH production
Primary Hypothyroidism
Subacute thyroiditis (DeQervain’s thyroiditis)=uncommon
-painful, fever, inflammation, they look systemically ill
-
Autoimmune thyroiditis
Hashimotos, chronic lymphocytic thyroiditis)
Hashimotos’s is the most common cause of hypothyroidism in the USA
-immune driven that almost always follows a viral infection
Painless thyroiditis
Pathology says its viral (similar to hashimoto) BUT they are inflammatory with systemic symptomatology
Postpartum Thyroiditis
Immune complexes attack thyroid for a short period of time
usually resolves on their own
Myxedema Coma
Long-standing hypothyroidism that has been untreated
Both are disorders of the posterior pituitary
SIADH
-Ectopic Secretion of ADH is the most common cause (too much ADH); will hold onto water
also common after surgery
For Diagnosis: normal adrenal and thyroid function must exsist
- Clinical Manifetations
- r/t enhanced renal water retention
- hyponatremia (almost all cases = dilutional hyponatremia)
Hypoosmolarity/hyperosmolarity
- little solute being diluted by all the water
- specific gravity would be HIGH because the urine in concentrated
K+ is generally unaffected
-N/V, anorexia are symptoms that will develop when fluid retention occurs
Diabetes Insipidious
- insufficient of lack of ADH (dumping water without regard to how much fluid is on board)
- polyuria and polydipsia
- partial or total inability to concentrate the urine
Specific gravity of the urine would be very low; because a lot of water beingpumped through kidneys
Neurogenic
Insufficient amounts of ADH
May result from head trauma
water deprivation does not help
Nephrogenic
inadequate response to ADH
Hormones released
ACTH
TSH (THYROTROPIN)
GRH OR GRF (SOMATOTROPIN)
B-LIPOPROTEIN
Prolactin (no known releasing factor/dopamine is antagonist)
Leutinizing hormone
FSH
B-endorphins
Posterior Pituitary Hormones
- these hormones are produced in the hypothalmus and stored in the posterior pituitary until the appropriate signals tell them to release
- Hormones STORED:
ASH and OXYTOCIN
- HORMONES RELEASED:
- ADH (formerly called vasopressin)
- controls plasma osmolality
1-strikes VI receptors in the periphery, causing vaso constriction because it releases calcium; calcium is important in any type of contraction becaue it binds to troponin and tropamycin which allows actin and mysin, which shorten and contraction occurs
- 2- acts on V2 receptors in renal tubules: causes renal tubule to hold on to sodium, and wehre salt goes, wa-wa goes
- OXYTOCIN- uterine contractions and milk ejection in lactating women/let down
- Prolactin causes the production of milk
- reduces the brains responsiveness to stressful stimuli, especially in the pregnant and postpartum states
-pituitary is vascular and therefore vilnerable to ischemia and infarction
Hypopituitarism
Pituitary infarction
- sheehan syndrome
- hemorrhage
- shock
Others: Head trauma, infections and tumors (post-partum hemorrhage is an example)
Panhypopituitarism: all hormones are absent
ACTH defiency
TSH defiency
FSH and LH defieciency
GH deficiency
(-no feedback looping is working at al, electrolyte imbalances, malaise, muslce weakness:major endocrinopathies)
Hyperpituitarism
Commonly due to a benign, slow-growing pituitary adenoma
-Manifestations:
Headache and fatigue
visual changes
hyposecretions or hyper secretions of neighboring anterior pituitary hormones
Hypersecretion of growth Hormone
ACROMEGALY
hypersecretion of GH during adulthood
- slowly progressive
- Mortality: cardiac hypertrophy, HTN, athersclerosis, Type II leading to coronary artery disease
- malignancies are common
Clinical manifestations of acromegaly
connection tissue proliferation
- enlarged tongue, interstitial edema, increase in the size and function of sebaceous and sweat glands, coarse skin and body hair
- Bony proliferation: large joint arthropathy
- periosteal vertebral growth
- Kyphosis
- enlargement of facial bones and hands and feet
- protrusion of lower jaw and forehead
- need for increasingly large sizes of shoes, hats, rings and gloves
Giantism
GH hypersecretion in children and adolescents
Hypersecretion of prolactin
- caused by prolactinomas
- most common hormonally active pituitary tumor
- in females, increased levels of prolactin causes amenorrhea, galactorrhea, hirsutism and osteopenia
- in males, increased levels of prolactin cause hypoginadism, erictile dysfunction, impaired libido, oligospermia, and diminished ejaculate volume
Causes:
primary adrenal insufficiency (addison disease)
Secondary: inadequate stimulatin of the adrenal glands by ACTH or a primary inability of the adrenals to produce and secrete the adrenocortical hormones
Cushing;s Disease
Causes: excessive anterior pituitary secretion of ACTH
Cushing Syndrome: excessive level of cortisol, regardless of cause
Clinical Manifestations of Cushing’s
weight gain is the most common
accumulation of adipose tissue in the trunk, facial and ervical areas
(truncal obesity, moon face, buffalo hump)
transient weight gain from Na and water retention may be present
- Glucose inolerance
- ,etabolic syndome with abdominal obesity, HTN, glucose intolerance and dyslipidemia is a common complication
50% experience an alteration in mentl status
-Women may experience increased hair growth and oligomenorrhea
Addison’s Disease
Cause: Primary adrenal insufficiency
adrenocortical hypofunction
Clinical manifestations of Addison’s
result from hypocortisolism and hypoaldosteronism
-weakness and easy fatigability
hyperpigmentation and vitiligo
hypoglycemia
as condition progresses=anorexia, n/v. diarrhea
greatest concern is hypotension that can progress to complete vascular collapse and shock
disturbances in mood and motvation are common
-women may lose axilarru and pubic hair
Causes of hyperfunction of the adrenal medulla
caused by tumors fromthe chromaffin cells of the adrenal medulla
- pheochromocytomas (tachycardia, HTN, palpitations, A-Fib)
- secrete catecholamines on a continious or episodic basis
SXS
R/t chronic affects of catecholamine secretion
HTN most commoon sign (r/t increased pvr)
(HTN may be sustained or paroxysmal)
diaphoresos, tachycardia, palpitations and severe headache
causes
acute complications:
Acute compliations of DM: -hypoglycemia
-DKA
*insulin deficiency
*decreased glucose use, ketosis, metabolic acidosis, osmotic diuresis
*usually treated with Type I
*illness, trauma, surgery, emotions
*total body (not serum) potassium defiency
cerebral edema, especially in children
Hyperosmolar hyperglycemic nonketotic syndrome
usually associated with type 2
higher glucose
less ketosis
severe dehydration and potassium deficit
greater fluid loss
Chronic complications of DM
Hyperglycemia and nonenzymatic glycosylation
hyperglycemia and polyol pathway
-sorbitol and fructose increase intracellular osmotic pressure (attracts water leading to cell imjury cecause increased tonicity sucks fluid in)
Evident in Kinase C
-enzyme inappropriately activated by hyperglycemia
_RBC’s, eyes, kidneys can utilize sugar without insulin
MICROvascular disease:
Retinopathy
diabetic nephropathy
Lab Values
Type I DM
2 Types: Immune and non-immune
Demonstrates pancreatic atrophy and loss of beta cells
=macrophages, T & B Lymphocytes, and natural killer cells are present
genetic susceptibility
15% of family memner with DM type I will have it
environmental factors
immunolocigallu mediated destruction of beta cells
Clnical manifestations of type I DM
hyperglycemia
- 80-90% of the function of insulin secreting beta cells in the islet of Langerhans is lost
- polydipsia, polyuria, polyphagia, weight loss an fatigue
Type 2 DM
dysfunction of the pancreas
affects adults and children
genetic environmental interaction
increased insulin resistance
decreased secretion of insulin
metabolic syndrome
Treatment: exercise, treatment of obesity, medication
manifestations:
recurrent infections, vision problems, neuropathy
Hypoglycemia
Hypo SXS
cold, clammy skin
tremblinig or nervousness
loss of motor coordination and function
irritabilty or confusion
blurred vision
headache
-nausea/stomach pain
fainting/unconsciousness
Hyperglycemic
SXS
increased thirst and urination
sweet odor to breath
fatigue
agitation and confusion
high levels of ketones in the urine
weight loss
DKA
insulin deficiency
decreased glucose use, ketosis, metabolic acidosis, osmotic diuresis
usually treated with type I
illness, trauma surgery, emotions
Total body (not serum) potassium deficiency
cerebral edema, especially in children
HHNK
hyperosmolor hyperglycemic nonketotic syndrome
usually associated with type II
higher glucose
less ketosis
severe dehydration and potasium deficit
greater fluid loss
Difference with DKA and HHNK
patient with HHNK will have sufficient insulin to take care of enough glucose getting in the tissues and to suppress lipolysis (breakdown of fat)=get hyperglycemia dn superdehrdrated; no ketosis and usually not acidoic
DKA: Uses fat as a source, does have metabolic acidosis, do become ketotic
-CMP-High CO2 and a large anion gap; tells you that there are other anions that are NOT being accounted for
CO2 is really a measure of Bicarn
-bicarb+dissolved CO2+carbonic acid; 95% bicarb
Macro-vascular changes in DM
coronory artery disease (most common ause of death in personw with type 2 and prevalence increases with duration of the disease)
- Stroke
- peripheral arterial disease
Micro-vascular complications with DM
retinopathy
diabetic nephropathy
Insulin
regulated by chemical, hormonal, neural mechanisms
- synthesized from proinsulin
- cleaved into c peptide and insulin
- can check c peptide levels and get an accurate measure of insulin levels
- Secretion promoted by increased blood glucose levels
- Purpose of insulin as intracellular transport mechansim
- facillitates intracellular transport of K+
- facilitates the rate of glucose uptake into body’s cells
- sensitivity of the insulin receptor is key in maintaining normal cellular function (insulin resistance)
- electrolytes that insulin transports
- facilitates intracellular transport of K+
