Week 4 - Endocrine Flashcards
insert image pituitary 1
know hormones from pituitary gland and hypothalamus
EXAM* ID: -anterior pituitary -Sella turcica of SPHENOID BONE -Hypothalamus - posterior pituitary
Hypothalamus is located at the
base of the brain and above the pituitary gland.
Environmental factors that stimulate the hypothalamus to secrete hypothalamic releasing and hypothalamic inhibitory hormones are:
Light Temperature Adrenergic and dopaminergic receptors Pain signals Emotions, and Olfactory sensations
the collecting and coordinating center for information and links the central nervous system and endocrine system to the environment
Hypothalamus
** EXAM Hypothalamic hormones (releasing or inhibiting) originate in the ______ and control secretions from the _______.
originate in the: hypothalamus control secretions from the: anterior pituitary
These hormones travel via hypothalamic hypophyseal portal vessels (undiluted by peripheral blood) to interact with cell membrane receptors in the
anterior pituitary.
This increases the intracellular concentrations of calcium ions and ____
cyclic adenosine monophosphate (cAMP)
Pituitary Gland: Lies in the
sella turcica
sella turcica is at the base of
at the base of the brain and is connected to the hypothalamus by the pituitary stalk.
Pituitary gland lies inside or outside the BBB?
outside
the pituitary gland is divided into:
Divided into 1. anterior pituitary (adenohypophysis) and 2. posterior pituitary (neurohypophysis)
Hypothalamic and pituitary secretion is pulsatile rather than tonic and these pulses are superimposed on broader biologic rhythms such as the:
- circadian (which releases adrenocorticotrophic hormone (ACTH), 2. HGH -the sleep entrained release of human growth hormone (HGH) 3. Gonadotropins for the monthly cycle of females
anterior pituitary AKA
adenohypophysis
posterior pituitary AKA:
neurohypophysis
adenohypophysis
anterior pituitary
neurohypophysis
posterior pituitary
hormone released by circadian rhythm:
ACTH (adrenocoritcotrophic hormone)
hormone released during sleep:
HGH human growth hormone
hormones released that regulates female mensuration
gonadotropins
Anterior Pituitary: Synthesizes, stores, and secretes tropic hormones: (6)
- ACTH: polypeptide 2. Prolactin: polypeptide 3. HGH: polypeptide 4. (TSH) Thyroid Stimulating Hormone: glycoprotein 5. (LH) Luteinizing Hormone: glycoprotein 6. (FSH) Follicle stimulating hormone : glycoprotein
Anterior pituitary also secretes beta-lipotropin containing the amino acid sequences of several endorphins
that bind to opioid receptors.
Posterior Pituitary: Stores and secretes two hormones:
- Arginine vasopressin (AVP): Formally known as antidiuretic hormone (ADH) 2. Oxytocin
AVP/ADH and Oxytocin are initially synthesized in the _____ and subsequently transported (via axons) to the ___________.
-hypothalamus -posterior pituitary
HGH - cell type and principal action Tbl 37-2
somatotropes -accelerates body growth; insulin antagonism
Prolactin - cell type and principal action Tbl 37-2
Lactotropes -stimulates secretion of milk and maternal behavior inhibits ovulation
LH - cell type and principal action Tbl 37-2
gonadotropes stimulates ovulation in females testosterone secretion in males
FSH - cell type and principal action Tbl 37-2
gonadotropes - stimulates ovarian follicle growth in females and spermatogenesis in males
ACTH - cell type and principal action Tbl 37-2
Adrenocorticotrophic hormone -corticotropes -stimulates adrenal cortex secretion and growth; steroid production
TSH - cell type and principal action Tbl 37-2
thyrotropes -stimulates thyroid secretion and growth
Beta-lipopropin - cell type and principal action Tbl 37-2
corticotropes -precursor of endorphins
Arginine Vasopressin (AVP) - cell type and principal action Tbl 37-2
supraoptic nuclei -promotes water retention and regulates`
oxytocin - cell type and principal action Tbl 37-2
paraventricular nuclei -causes ejection of milk and uterine contraction
the Most abundant anterior pituitary hormone:
Growth hormone (Somatotropin):
this Stimulates growth of all tissues in the body.
GH
GH’s specific effect is stimulation of
linear bone growth –resulting from GH action on the epiphyseal cartilage plates of long bones.
Specific effect is stimulation of linear bone growth resulting from GH action on the
epiphyseal cartilage plates of long bones.
Excess secretion of GH before epiphyseal closure occurs becomes
gigantism
Excess secretion of GH after epiphyseal closure long bones
-increase in thickness, not length and -called acromegaly
Metabolic Effect of GH:
-Increase rates of protein synthesis (anabolic effect) -Increased mobilization of free fatty acids (ketogenic effect) -Antagonism of insulin action (diabetogenic effect) -Na+ and water retention
STIMULATION of GH results from: Table 37-3
- stress 2. physiologic sleep 3. hypoglycemia 4. decreased free fatty acid 5. increased amino acid 6. fasting 7. estrogens 8. dopamine 9. Alpha adrenergic agonists
INHIBITION of GH results from: table 37-3
- Pregnancy 2. Hyperglycemia 3. Increased free fatty acid 4. Cortisol 5. Obesity 6. Insulin-like growth factor 1 (IGF-1)
PERIOP stress and anxiety evokes the release
of GH
Plasma concentrations of GH characteristically increase during
physiologic sleep
Pregnancy stimulates the release of and
prolactin
dopamine inhibits its release
prolactin
Drugs may influence the secretion of GH, presumably via effects on the
hypothalamus
Large doses of corticosteroids suppress secretion of
GH
Dopaminergic agonists acutely increase the secretion of
GH
Preop anxiety increases plasma level of
prolactin
Prolactin secretion inhibits ovarian function thus may have
lack of ovulation and resulting in infertility
LH and FSH responsible for
pubertal maturation and secretion of steroid sex hormones by gonads of either sex.
ACTH regulates secretions of cortisol and stimulates formation of cholesterol in the
adrenal cortex.
**** the initial building block for corticosteroid synthesis:
Cholesterol
****Corticotropin-releasing hormone and ACTH are high in
am (~ 20 mcg/dL)
****Corticotropin-releasing hormone and ACTH are low in
low (~ 5 mcg/dL) in pm
Surgical incision, reversal of anesthesia, and postop pain stimulate .
ACTH release
Secretion of ACTH responds dramatically to stress under the control of corticotropin-releasing hormone from the: (2)
- hypothalamus, 2. negative feedback mechanism from circulating cortisol
ACTH Absence: The adrenal cortex undergoes
atrophy *Zona glomerulosa where aldosterone is secreted is least affected
***the hallmark of hypopituitarism.
Pallor is
Hyperpigmentation in presence of adrenal insufficiency from primary adrenal gland disease reflects
high concentrations of ACTH in plasma (as the anterior pituitary attempts to stimulate corticosteroid secretion)
high concentrations of ACTH in plasma as the anterior pituitary attempts to stimulate corticosteroid secretion presents as:
Hyperpigmentation from primary adrenal gland disease
Chronic administration of corticosteroids suppresses corticotropin-releasing hormone and leads to
atrophy of the hypothalamic-pituitary axis
**** Stressful events during the periop might evoke life threatening
hypotension
*** to pts considered at risk for suppression of the hypothalamic pituitary axis, what do we need to ensure we do?
administer supplemental exogenous corticosteroids
SNS stimulation and corticosteroids suppresses secretion of ____ and diminish _________.
TSH activity of thyroid gland
Secretion of TSH from the anterior pituitary is under control of ? from?
-thyrotropin-releasing hormone -from the hypothalamus **negative feedback mechanism (depending on the concentration of thyroid hormone circulating in the plasma).
What hormone? Widely distributed in the CNS Potent analeptic (stimulate characteristics) Stimulates respiratory rate Induces tremor Reduces sleep time.
thyrotropin-releasing hormone
Thyrotropin-releasing hormone does:
(STIMULATES) 1.Widely distributed in the CNS 2. Potent analeptic (stimulate characteristics) 3. Stimulates respiratory rate 4. Induces tremor 5. Reduces sleep time.
***Immunoglobulin A binds to
receptor sites on thyroid cells
*** IgA binding mimics effects of
TSH and accounts for hyperthyroidism
patients with hyperthyroidism often have detectable circulating concentrations of:
IgA proteins bound to thyroid cells
***primary hypothyroidism is
- increased [plasma] TSH -indicative of primary defect at the thyroid gland. - In response, the ANTERIOR PITUITARY stimulates release TSH
*** secondary hypothyroidism is:
- low levels of BOTH TSH and Thyroid Hormones -defect at the hypothalamus or anterior pituitary
**Hypothyroidism with increased plasma concentrations of TSH indicates a primary defect at the thyroid gland and an attempt by the anterior pituitary to stimulate hormonal output by releasing TSH. This is known as
primary hypothyroidism
***A defect at the hypothalamus or anterior pituitary is indicated by low concentrations of both TSH and thyroid hormones circulating in plasma and is known as
secondary hypothyroidism
Posterior pituitary supports terminal nerve endings of supraoptic and paraventricular nuclei of hypothalamus. Name Hormones of Posterior pituitary:
- AVP 2. Oxytocin
Arginine Vasopressin (AVP): synthesized in the
in the supraoptic nuclei
Oxytocin synthesized in the
paraventricular nuclei
Both hormones (AVP/oxytocin) are transported in secretory granules along axons from corresponding nuclei in the hypothalamus to the
posterior pituitary -for release when appropriate stimuli arise
Arginine Vasopressin (AVP): Functions include:
1-corticotropin secretion 2-vasoconstriction, 3-water retention
Three subtypes of AVP receptors:
V1, V2, V3
**V1 : Location - Job - Use -
- vascular smooth muscle - stimulation causes vasoconstriction - vasopressor (hypotension, sepsis, cpr) *DDAVP
**** KNOW V2 : Location - Job - Use -
-located on collecting duct cells in kidney - increases REabsorption of water by attaching to receptors on capillary side of epithelial cells lining the: 1.) distal convoluted renal tubules 2.) collecting ducts of the renal medulla
V3 : Location - Job - Use -
- AVP binds to these receptors in the adenohypophysis (anterior pituitary) -release corticotropin, -suggesting that this hormone affects the stress response.
*** Destructions of neurons in or near the supraoptic and paraventricular nuclei of the hypothalamus from pituitary surgery, cerebral ischemia, or malignancy may decrease vasopressin release to
cause central diabetes insipidus **PEE!!!** very dilute
If posterior pituitary alone is damaged, will there still be any secretion of AVP?
the transected fibers of the pituitary stalk can still continue to secrete AVP
Excessive secretion of AVP with subsequent retention of water and dilutional hyponatremia may result from:
1.Head injuries 2.Intracranial tumors 3.Meningitis *** 4.Pulmonary infections
***** Aberrant production of AVP is observed most commonly in pts with what form of cancer ?
- oat cell carcinoma –> in which the tumor itself produces AVP
Secretion of this is stimulated by breast feeding, cervical and vaginal dilation
oxytocin
oxytocin Binds to G proteins on surface of uterine myocytes to trigger the release
of calcium from the sarcoplasmic reticulum, exerting a contracting effect on the pregnant uterus. ** keep in mind this is similar to MOA for MH**
Augments the action potential of the uterine smooth muscle?
oxytocin
Large amounts of oxytocin cause sustained uterine contraction necessary for postpartum
hemostasis
oxytocin has only 0.5% - 1.0% the antidiuretic activity of ___ and can be released __________.
-AVP -abruptly and independently of AVP
pitocin availability and mixing
10units/ml ~ usually mixing 20u/1000ml for C/S
Note the 3 lobes “butterfly”: 1. Pyramidal lobe 2. Left lobe 3. right lobe
thyroid gland Principal hormone secretions are:
- thyroxine (T4) and triiodothyronine (T3).
T4 a prohormone synthesized from
tyrosine —> represents 80% of body’s thyroid hormone production
T3 is 5 times more active than
T4
metabolism of T4 and T3 to inactive compounds is done by? where?
- Two distinct deiodases (an enzyme catalyst) - in the liver, kidneys, and CNS
T3 is produced directly from:
- tyrosine metabolism or from 2. conversion of T4 in peripheral tissues
Half life of T3 and T4 is:
T3 = 1.5 days T4 = 7 days
**Both T3 and T4 are highly bound to
albumin
Thyroid gland also secretes
calcitonin which is important for calcium ion use
**** Thyroid hormones increase O2 consumption in all tissues except for ? What does this mean?
-the brain. -Thus there are minimal changes in anesthetic requirements (MAC) for pts with hyper/hypo thyroid
although thyroid hormones may not impact anesthetic needs, what might it impact?
cardiac O2 consumption
***Earliest clinical manifestations of abnormal thyroid hormone levels are often:
Cardiac changes
***Absent thyroid hormone decreases O2 consumption
40%;
*** Excess of thyroid hormones can expand O2 consumption
as much as 100%
The thyroid receives innervation from the
autonomic nervous system
The thyroid is two lobes connected by
thyroid isthmus
the thyroid is highly _____.
vascular!! *think of bleeding
*** T4 serves principally as a prohormone
for T3
Thyroid hormones exert most if not all of its effects through
control of protein synthesis.
Thyroid hormones activate
DNA transcription process in the cell nucleus to form new cell proteins and enzymes
Been proposed that thyroid hormones modulate conversion of
alpha-adrenergic to beta-adrenergic receptors
Cardiac cholinergic receptors numbers are decreased by thyroid hormones which is consistent with an increase in HR that is out of proportion to .
the increase in C.O
Thyroid hormones accelerate metabolism thus tissues vasodilate and as a result CO often increases. There is no increase in ? why?
SBP because peripheral vasodilation offsets the impact of more blood flow. **think thyroid storm**
calcitonin is a polypeptide hormone secreted by the? it does what? *book
thyroid gland - decreases calcium ion concentration in plasma by weakening activity of osteoclasts and strengthening the actiit of osteoblasts.
Calcitonin works in the early moments after *flood p 739
ingestion of high calcium meals
Total thyroidectomy and subsequent absence of calcintonin does not measurably influence the plasma concentration of calcium, b/c of the *flood p 739
predominance of parathyroid hormone.
PTH and Ca have what kind of relationship?
inverse increase of one , decreases the other
how many parathyroid glands secrete parathyroid hormone (PTH) that regulate plasma concentration of calcium ions?
4
Secretion of PTH is inversely related to
plasma ionized calcium concentration
Small declines in the plasma concentrations of calcium ions stimulate
the release of PTH.
PTH promotes mobilization of bone calcium (osteoclast) by:
- enhances conversion of vitamin D to its active form to increase GI absorption of Ca (active form of vit d 1,25-dihydroxycholecalciferol)
PTH increases renal tubular Ca absorption by:
-inhibiting renal reabsorption of phosphate -to increase Ca and to decrease phosphate concentrations in plasma.
PTH has targeted effects on:
Bones Renal tubules GI
Adrenal cortex: Secretes 3 major classes of corticosteroids
- Mineralocorticoids (aldosterone) 2. Glucocorticoids (cortisol) 3. Androgens
**** the precursor of all corticosteroids:
Cholesterol is
2 important corticosteroids:
Aldosterone (mineralocorticoid) Cortisol (principal glucocorticoid)
Adrenal cortex has 3 zones:
Zona glormerulosa: Zona fasiculata: Zona reticulari **Zona “G.F.R.”
** Zona glormerulosa: secretes
mineralocorticoids
Zona fasiculata: secretes
glucocorticoids
Zona reticularis: secrete
s androgens and estrogens
According to the ADA and WHO diabetes is classified by the underlying disease etiology (types 1 or 2)…. how is DM NOT classified?
-Not classified by age-of-onset (juvenile vs. adult) -not classified by treatment modality (IDM vs NIDM)
Type 1 Diabetes FYI’s:
-Onset younger age than type 2 -Sensitivity to insulin is normal -Lack of insulin may precipitate diabetic ketoacidosis
Pancreatic beta cell dysfunction leads to
type 2 diabetes
Type 2 DM distinguishing features:
- peripheral insulin resistance - pancreatic beta cell dysfunction –> failure to secrete insulin
ratio of type 1 vs type 2 diabetics
1:9
Diabetes can be caused by: including table 38-1 *ppt
-*Gestation -*Exocrine defects in insulin action and beta cell function (pancreatitis, cystic fibrosis) -*Infections (rubella, CMV) -*Uncommon immune-mediated disorders (“stiff man” syndrom, anti insulin receptor antibodies) - Drug induced (glucocorticoids, thyroid hormone, beta-adrenergic agonists) -Genetic defects in pancreatic Beta cell fxn -Genetic defects in insulin action (resistance)
****Most protein used for glucose formation comes from
skeletal muscles
Liver which is insulin deficient uses fatty acids to produce ketones which can serve as an energy source
for skeletal muscle and cardiac muscle.
Production of ketones can lead to
ketoacidosis;
urinary excretion of ketones contributes to
electrolyte depletion especially K+. This hypokalemia may go unnoticed d/t intracellular K+ ions are exchanged for extracellular ions to compensate for the acidosis
Impacts of Hyperglycemia:
-Impairs vasodilation -Induces a chronic proinflammatory, prothrombotic, and proatherogenic state leading to vascular complications -Atherosclerotic vascular, renal and nervous system effects with peripheral vascular disease renal insufficiency and cerebrovascular disease
of the hyperglycemia impairments, the greatest relevance for anesthesia are:
atherosclerotic vascular, renal and nervous system effects w/PVD, renal insufficiency, and cerebrovascular disease.
Symptoms of adverse consequences usually resolve with blood glucose levels less than
200 mg/dL
A1C measures:
long term control of diabetes - 3 month avg -less than 7% are associated with fewer microvascular complications
Type 1 Diabetes: Do not produce
insulin
*** Type 2 Diabetes: Rx insulin when oral glucose regulators fail. Auto antibodies have developed or WHAT have been dysfunctional?
Pancreatic beta cells
Larger doses of insulin last longer and exert a greater net effect than small doses. The number of insulin receptors seems to be inversely r/t
the plasma concentration of insulin
Obesity and type 1 diabetes mellitus are associated with fewer
insulin receptors
Insulin is metabolized in? by?
- kidney and liver -by a proteolytic enzyme
**** what % of insulin reaches the liver through the portal vein and is metabolized in a single passage – FIRST PASS
~ 50%
what effects clearance rate of circulating insulin more ? renal or liver disease?
Renal dysfunction effects clearance rate of circulating insulin more so than liver dysfunction/disease
in renal disease, what do you what to do to your insulin dosing?
decrease it
*** Although it has rapid clearance , IV insulin has a pharmacologic effect that lasts for .
30-60 minutes - because insulin is tightly bound to tissue receptors
***Total units of insulin secretion per day
is ~ 40 units
***Rate of insulin secretion increases ___ after food intake
5-10 fold
***Insulin secreted into the portal venous system in the basal state at a rate
of ~ 1 unit/hour
***SNS and PNS innervate the insulin-producing islet cells to influence : (2)
1.basal rate of hormone secretion as well as 2. response to stress.
***Alpha adrenergic stimulation to insulin basal secretion
decreases basal secretion of insulin
***Beta adrenergic or PNS stimulation to insulin basal secretion:
increases basal secretion of insulin
insulin response to IV Insulin vs oral ingestion - which is greater response to glucose?
Oral -b/c glucose dependent insulinotropic polypeptide is released after oral ingestion of glucose and the pancreatic beta cell response is augmented.
Type 1 diabetes: usually requires 2 daily SQ injections of
intermediate or long acting insulin combined with a rapid acting insulin .
manufactured insulin using recombinant DNA to replace beef and pork insulin resulted in decrease in :
allergies
potency of insulin:
22-26U/mg U-100 (100U/mL) is most common commercial preparation
Sulfonylureas - FYI’s
- can lower BG to hypogylcemic levels - require some beta cell function - not effective in DM1 - Do not give w/know slufa allergy - m/c : Metformin
known for causing vit b12 deficiency:
metformin
*** ~ 20% of pts with Type 2 DM who begin sulfonylurea therapy do not have an adequate hypoglycemic response to maximal doses - this is known as:
(Primary Failure)
***Each year an additional 10 – 15% who responded initially , fail to respond to sulfonylurea therapy
Secondary Failure)
sulfonylurea receptors are found on
pancreatic and cardiac cells
sulfonylureas inhibit adenosine triphosphate sensitive potassium ion channels (sulfonylurea receptor-1) on
pancreatic beta cells
after binding to the pancreatic beta cells, what causes the stimulation of exocytosis/ release of insulin storage granules?
the an influx of Ca+
Oral hypoglycemic are readily absorbed from the
GI tract
Weakly acidic sulfonylureas circulate bound to ____? what %?
protein (primarily albumin) 90-98%.
sulfonylureas are metabolized extensively in the
liver
*** ~ 50% of glyburide is excreted
in feces
***Most common severe complication of sulfonylureas is
hypoglycemia
Greatest risk of hypoglycemia occurs with: why?
glyburide and chlorpropamide drugs with the longest elimination half times
Sulfonylureas can act up to
7 days
**Hypoglycemia from sulfonylureas may be infrequent, it is often more
-prolonged and -more dangerous than hypoglycemia from insulin
how do you tx sulfonylurea induced hypoglycemia?
prolonged infusion of glucose solution
**Risk factors for sulfonylurea induced hypoglycemia:
-Impaired nutrition as in periop period -Older that 60 years -Impaired renal function -Concomitant drug therapy that potentiates sulfonylureas (warfarin, and sulfonamide abx) or those that DECREASE blood glucose such as ETOH and salicylates -Renal dz decreases elimination and active metabolites thus increases chance of hypoglycemia
Renal dz decreases elimination and active metabolites of sulfonylureas thus
increases chance of hypoglycemia
-Concomitant drug therapy of what drugs potentiates sulfonylureas ? or Those that DECREASE blood glucose ?
- warfarin, and sulfonamide abx - such as ETOH and salicylates (decrease blood sugar)
Flood. pg 754-potentiates- phenylbutazone, sulfonamide abx, warfarin.
Sulfonylureas cross the placenta and can produce
fetal hypoglycemia.
can sulfonylureas cross the placenta?
yes
Sulfonylureas close the K-ATP channels and
inhibit ischemic preconditioning, a cardioprotective mechanism.
for renal patients, what oral drugs are preferable? why?
Tolbutamide and Glipizide - only small amounts of drug are excreted unchanged in the urine
what event (type?) has been associate with sulfonylureas,
CV mortality especially those with prior MI
***Sulfonylureas not recommended for pts with liver dysfunction d/t prolongs elimination half time and enhances chance of hypoglycemia except for
acetohexamide
** acetohexamide is the only sulfonylurea recommended for:
for pts with liver dysfunction *it does not increase r/o hypoglycemia
Disulfiram-like reactions and inappropriate secretion of arginine vasopressin hormone that results in hyponatremia are…
are unique side effects of chlorpropamide
** A unique side effect of chlorpropamides
-disulfiram like reactions -inappropriate secretion of AVH —> hyponatremia
Disulfiram (Antabuse) like reactions:
Flushing of skin Tachy Sob n/v Throbbing head ache Visual disturbances Confusion Syncope Circulatory collapse
glucagon is a catabolic hormone acting to mobilize
glucose fatty acids amino acids into the systemic cirulation
principal stimulus for secretion of glucagon is
hypoglycemia
glucagon abruptly increases the blood glucose concentration by stimulating
glycogenolysis in the liver
glucagon activates adenylate cyclase for the subsequent fromation of
cAMP
glucagon undergoes enzymatic degradation to inactive metabolites in the
liver and kidneys and at receptor sites in cell membranes
**the elimination half time of glucagon is
brief: only 3-6 minutes
**the longest acting sulfonylurea is
chlorpropamide ~ 72hr doa
***shortest acting and least potent sulfonylurea is
tolbutamide
**what sulfonylurea is appropriate for a diabetic patient with gout?
actohexamide
while taking chlorpropamide-risk factors for development of hyponatremia include: if all these RF are present, the frequency of hyponatremia increases how much?
- > 60 yrs - female gender - concomitant admin of thiazide diuretics ** THREEfold
like metformin, this type of drug, act in the presnce of insulin and are especially effective in Obese patients
TZDs = thiazolidinediones - tzds tend to decrease triglycerides and increase HDL and LDL levels
Amylin agonists (pancreatic beta cells secrete insulin and amylin) do not alter insulin levels they do
-suppress gastric emptying -inhibit glucagon release -reduce HbA1C levels
