25. What is aldosterone and why do we need it?

709
Aldosterone is the most potent of the naturally occurring mineralocorticoids and
acts to conserve sodium by increasing the activity of the sodium pump of the
epithelial cells in the nephron.
The initial stages of aldosterone synthesis occur in the zona fasciculata and zona
reticularis. The final conversion occurs in the zona glomerulosa.
Aldosterone synthesis and secretion are regulated primarily by the renin-
angiotensin-aldosterone system.
o The renin-angiotensin system is activated by:
Na+ and water depletion
increased K+ levels
diminished effective blood volume
Angiotensin II is primary stimulant of aldosterone synthesis and secretion.
However Na+ and K+ levels may directly affect aldosterone secretion
When Na+ and K+ levels are WNL approx. 50- 250mg of aldosterone is secreted
daily.
o Of the secreted aldosterone 50-75% binds to plasma proteins
Aldosterone is degraded in the liver and is excreted by the kidney.
Aldosterone maintains extracellular volume by acting on distal
nephron epithelial cells to increase Na+ reabsorption and K+ and
hydrogen excretion.
o This renal effect takes 90 minutes to 6 hours
Other effects include:
o enhancement of cardiac muscle contraction, stimulation of ectopic
ventricular activity through 2ndary cardiac pacemakers in the ventricle,
stiffening of blood vessels with increased vascular resistance, and decreased
fibrinolysis.
Pathologically elevated levels of aldosterone implicated in myocardial changes
associated with heart failure.
26. What is the role of calcitonin? Pg 702
Produced by the thyroid by the parafollicular cells (C cells)
Calcitonin is also called thyrocalcitonin
acts to lower serum calcium levels by inhibition of bone-resorbing
osteoclasts.
o High levels of calcitonin are required for these effects
deficiencies of calcitonin do not lead to hypocalcemia.
o The metabolic consequences of calcitonin deficiency or excess do not
appear to be significant in humans.
Calcitonin is used to treat:
o Osteoporosis
o Osteoarthritis
o Paget bone disease
o Hypercalcemia
o osteogenesis imperfecta
o metastatic cancer of the bone
Precursor molecule to calcitonin procalcitonin is a stress hormone that is elevated
in infectious and inflammatory disorders and its measurement can aid in the dx of
these serious diseases.
Table 12-6 pg 701 Thyroid gland hormones and their regulation and functions
o Calcitonin
 Regulation
Elevated serum calcium-major stimulant for calcitonin
o Other stimulants
Gastrin
Calcium rich foods (regardless of serum Ca
levels
Pregnancy
Lowered serum calcium-suppresses calcitonin
release
Functions
Lowers serum calcium by opposing bone-resorbing effects of
PTH, prostaglandins and calciferols by inhibiting osteoclastic
activity
Lowers serum phosphate levels
May also decrease calcium and phosphorus absorption in the
GI tract

27. What is oxytocin? How does it relate to the pituitary gland? Pg 696,698, 699
Oxytocin is a polypeptide hormone of the posterior pituitary gland.
Oxytocin is synthesized in the hypothalamic neurons (supraoptic and
paraventricular nuclei)
Oxytocin travel to the posterior pituitary by way of the hypothalamohypophysial
nerve tract.
Is stored and secreted by the posterior pituitary gland
o Oxytocin travel to the posterior pituitary by way of the
hypothalamohypophysial nerve tract.
The release of oxytocin is mediated by cholinergic and adrenergic
neurotransmitters. Major stimulus to release is glutamate.

Oxytocin is responsible:
o for contraction of the uterus
In response to distention of the uterus, oxytocin stimulate
contractions and functions near end of labor to enhance the
effectiveness of contractions, promote delivery of placenta and
stimulate postpartum uterine contractions, thereby preventing
excessive bleeding.

o milk rejection in lactating women

Stimulated by sucking, oxytocin binds to its receptors on
myoepithelial cells in the mammary tissues and cause contraction of
the these cells. This results in increased intramammary pressure and
milk expression (let down reflex)
o may affect sperm motility in men.
Oxytocin implicated in behavior responses in women and has been suggested that it
plays a role in the brains responsiveness to stressful stimuli, especially in the
pregnant and postpartum states.
May have a potential role in the treatment of maternal child neglect and a variety of
anxiety disorders is being explored
28. Understand the role of insulin, how does insulin affect potassium.
The beta cells of the pancreas synthesize insulin from the precursor proinsulin.
o Proninsulin is composed of an A peptide and B peptide connected by a C
peptide and 2 disulfide bonds
o C peptide is cleaved by proteolytic enzymes leaving the bonded A and B
peptide chain that becomes insulin
Insulin circulates freely in the plasma and is not bound to a carrier.
Secretion of insulin is regulated by chemical, hormonal, and neural control.
o It is promoted when blood levels of glucose, amino acids (arginine and
lysine) and GI hormones (glucagon, gastrin, cholecystokinin, secretin)
increase and when the beta cells are stimulated parasympathetically.
o Insulin secretion diminishes in response to low blood levels of glucose
(hypoglycemia), high levels of insulin (through negative feedback to beta
cells), and sympathetic stimulation of the alpha cells in the islets.
Prostaglandin also inhibits insulin secretion.
Insulin facilitates the rate of glucose uptake into many cells within the body.
o At the target cell, insulin binds with an enzyme-linked plasma membrane
receptor
o Insulin receptor binding sends a cascade of signals to activate glucose
transporters (GLUT 4) for entry into the cell
GLUT 4 is stored in cellular vesicles until activated by the insulin
receptor and is then translocated to the cell surface where it
facilitates the diffusion of glucose into the cell
See figure 21-15 on pg 705
Sensitivity of the insulin receptor is key component in maintaining normal cellular
function, and insulin resistance has been implicated in numerous cardiovascular
diseases, including HTN and DM.
o Adipocytes release a number of hormones that are altered in obesity and
have an important effect on insulin sensitivity.
Insulin is an anabolic hormone that promotes not only the uptake of glucose but
synthesis of proteins, carbs, lipids and nucleic acids. It Functions mainly in the
liver, muscle and adipose tissue.
o Net effect of insulin in these tissues is to stimulate protein and fat synthesis
and decease blood glucose level
o See table 21-7 pg 705
The brain, RBC, kidney and lens of the eye do not require insulin for glucose
transport
Insulin also facilitates the intracellular transport of K+, phosphate, and magnesium.
(p. 706)
Insulin is metabolized in the liver and kidney by enzymes that split the disulfide
bond.
o Very little is excreted unchanged in the urine

29. What is the role of TSH? Where is it secreted? Know the negative feedback loop
(Table 216 and p. 700-701)
TSH is a glycoprotein hormone synthesized and stored within the anterior pituitary.
Once TSH is secreted by the anterior pituitary, it circulates to bind with TSH
receptors sites located on the plasma membrane of the thyroid follicular cells
The effects of TSH on the thyroid include:
o immediate increase in the release of stored thyroid hormone
 o increase in iodide uptake and oxidation
o increase in thyroid hormone synthesis
o increase in the synthesis and secretion of prostaglandins by the thyroid.
TSH is important in stimulating the growth and maintenance of the thyroid gland b
stimulating thyrocyte hypertrophy and hyperplasia and decreasing apoptosis.
T3 and T4 levels and controlled by TSH
o See table 21-6 pg 701
Regulation of thyroid hormone secretion
o Regulated through a negative feedback loop involving the hypothalamus,
the anterior pituitary and the thyroid gland
o Thyroid stimulating hormone (TSH) secretion from the anterior pituitary is
stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus.
Secretion of TSH stimulates the synthesis and secretion of Thyroid
hormones. Increasing levels of T4 (thyroxine) and T3 (triiodothyronine)
then generate negative feedback on the pituitary and hypothalamus to
inhibit TRH and TSH synthesis.
See figure 21-2 on pg 691
Negative feed-back is possible at 3 levels
Target organ (ultrashort feedback)
Anterior pituitary target (short feedback)
Hypothalamus (long feedback)

30. Understand the roles of epinephrine and norepinephrine. Pg 710

Chromaffin cells (pheochromocytes) are the cells of the adrenal medulla.
The major products stored and secreted by these cells are catecholamines
epinephrine (adrenaline) and norepinephrine which are synthesized from the amino
acid phenlalinerine
 o Only 30% of circulating epinephrine comes from adrenal medulla, the other
70% is released from nerve terminals.
o Medulla is only minor source of norepinephrine.
Adrenal catecholamines are stored in secretory granules within Chromaffin cells.
o Physiologic stress to the body (trauma, hypoxia, hypoglycemia, etc) triggers
release of adrenal catecholamines through acetylcholine, which depolarizes
the chromaffin cells.
o Depolarization causes release of epinephrine and norepinephrine into
bloodstream therefore; catecholamines from the adrenal medulla are
hormones and not neurotransmitters.
o Secretion of adrenal catecholamines also increased by ACTH and the
glucocorticoids.
o Once catecholamines are released they stay in the plasma for only seconds
to minutes, then are rapidly removed from the plasma by being taken up by
neurons for storage in new cytoplasmic granules or they may be
metabolically inactived and secreted in the urine
Catecholamines have diverse effects on the entire body, their release and the
bodys response have been characterized as fight or flight
In general, metabolic effects promote hyperglycemia through variety of
mechanisms (book says to see chapter 11) (table 11-2 on pg 345)
o Norepinephrine
Raises BP by constricting the peripheral vessles
Dilates the pupils of the eye
Causes piloerection
Increases sweat gland action in the armpits and palms
o Epinephrine
Has greater influence on the cardiac action (inotropic and
chronotropic)
Vasodilation occurs
Metabolic regulation occurs, increasing the glucose level
Tabl 11-2 on pg 345- Physiological effects of catecholamines
o Brain
Increased blood, increased glucose metabolism
o Cardiovascular system
Increased HR and force of contraction
Peripheral vasoconstriction
o Pulmonary system
Bronchodilation
o Skeletal muscle
Increased gylcogenolysis
Increased contraction
Increased dilation of muscle vasculature
Decreased glucose uptake and utilization (decreases insulin release)
o Liver
Increased glucose production
Increased glycogenolysis
o Adipose tissue
Increased lipolysis
Decreased glucose uptake
o Skin
Decreased blood flow
 o GI and genitourinary tracts
Decreased smooth muscle contraction
Increased renin release
Increased gastrointestinal sphincter tone
o Lymphoid tissue
Acute and chronic stress inhibits several components of innate
immunity, particularly decreasing the number of natural killer cells
o Macrophages
Inhibit and stimulate macrophapge activity depends on availability
of type 1/ proinflammatory cytokines, presence or absence of
antigenic stressors, and peripheral corticotropin-releasing hormone
Catecholamines exert their biological effects after binding to a plasma membrane
receptor
o A1, A2, B1, B2, B3
o See table 15-7 on pg 475 for greater detail