Download Cell Bio Exam 2 Outline: Lectures 17

Cell Bio Exam 2 Outline: Lectures 17-25
Lecture 17: Anterior Pituitary – GH & Prolactin
 GH (Somatotropin)
o 2 types of receptors on a cell make it well controlled
 GHRH: Gs stimulates
 From nucleus arcuate
 GHIH: GI inhibits
 From periventricular nucleus
o General Info:
 It is a stress hormone that peaks when you sleep, are fasting, stressed, or during
strenuous exercise
 Has pulses & is episodic
 GH is profoundly anabolic (building m.) & partially diabetogenic (decreases
glucose uptake by liver & partially desensitizes glucose receptors)
 Structure of GH is similar to prolactin, hPL, plactenal GH variant
 Increase in prolactin, can have GH effects
o Mechanism:
 Effects primarily to liver  IGF-1
 IGF-1 (peptide hormone) has a carrier (IGF-BP)
 Action of IGF-1: carries out the actions of GH
 IGF-1 can also be called somatomedian b/c mediates actions of GH
 IGF-1 is stimulated  stimulates somatostatin  GHIH 00> modulate GH
secretion
 Effects mediated through binding to a plasma membrane receptor, JAK-STAT
pathway
o Actions of GH:
 Increase height in kids
 Increase Ca++ retention, strengthens & increases mineralization of bone
 Increases m. mass through sarcomere hyperplasia
 Promotes lipolysis and increases lean body mass
 Increases protein synthesis
 Stimulates growth of all internal organs (except brain)
 Role in homeostasis
 Reduces liver uptake of glucose!
 Promotes gluconeogenesis in liver
o Q. What would happen if GH excess? Insulin Resistance
o GH Excess
 Acromegaly if after puberty
 Anterior pituitary adenoma or prolactinoma on CT/MRI
 Visual field defects
 Prominent supraorbital ridge
 Cardiac hypertrophy
 Abnormal glucose tolerance test!
 Spade shaped hands and feet
 Txt: w/somatostatin analogs
o GH Deficiency
 Africa pygmies (probably iodine def.)
 Levi-Lorain dwarfs (low IGF-1)
 Dwarfism
 Panhypopituitarism
o Restricted release of all hypothalamic/pituitary hormones b/c
constricted vasculature of hypothalamic/pituitary axis
 ACTH low = Cortisol low
 FSH/LH low
 If you lack GH  small stature w/normal proportions vs. TH defect w/more
overweight b/c decreased BMR
o GH Secretion Promoted By:
 Low glucose
 Low FFA’s
 Increased arginine (w/infusions)
 Stressful stimuli
 Exercise
 Androgens/estrogens
 Alpha-andrenergic agonists
o GH Inhibited By:
 Glucagon
 Increase in glucose
 FFA’s
 Aging
 Obesity
 Sustained increase in cortisol
 Prolactin
o General Info:
 Produced by anterior pituitary
 Circulates unbound in blood
 Tonically inhibited by dopamine
 Short half-life
 GH can cross-react with prolactin hormone receptors
o PH stimulated by:
 Estrogen, pregnancy
 Sleep
 Stress
 Pt’s w/increased TRH can have increased PH b/c TRH stimulates anterior pituitary
o PH decreased by:
 Dopamine!
 Bromocriptine (dopamine agonist)
 Somatostatin
 Prolactin via negative feedback
o Actions:
 Mammogenesis
 Lactogenesis
 Galactopoeisis
 Prolactin decreases 8-10 weeks post-delivery
o Prolactin Excess:
 Causes: hypothalamic destruction or prolactinoma
 Failure of ovulate & amenorrhea b/c inhibits GnRH secretion
 Can have issues w/fertility w/excess
 Can txt w/bromocriptine (which is a dopamine agonist to tonically inhibit)
Cell Bio Lecture 18: Posterior Pituitary – Oxytocin & ADH
 Oxytocin & ADH have overlapping receptors
 Both made in paraventricular & supraoptic nuclei of hypothalamus


o Transported & stored in posterior pituitary
Q. An 8 yo male is treated w/radiation and has complete loss of pituitary fxn, what would
happen? Absent sexual maturation
ADH
o Supraoptic nuclei is where it is made
o Can be taken nasally, if needed b/c it is only 10 AA long
o Stimulated By:
 Osmoreceptors (stronger stimulation)
 Normal plasma osmolarity: 280-284 mOsm
 At 284 mOsm, ADH begins to be produced to start & reabsorb water so no
dehydration
 At 295 mOsm, thirst is stimulated (1-2% above normal)
 Angiotensin II, which acts on osmoreceptors
 Baroreceptors
 5-10% drop in blood volume (ECF), ADH starts to be produced
 Postural changes via barorecetors
 Stress via endogenous opioids
o Inhibited By:
 Alcohol
 ANP
 ANP is made & secreted by cardiac atrial m. cells in response to increased
central venous pressure or increase in plasma Na+
 Increase GFR (opposite of ADH)
 Decreases Na+ & water reabsorption all along nephron  polyuria
o Actions:
 Water retention
 Acts on kidney to cause decrease in urine flow & increase in urine concentration
 Binds to receptor V2  Activates GS  increase cAMP  activates protein kinase A 
phosphorylates aquaporin channels at lumen of distal convoluted tubule  allow
water to flow into cell to increase water retention
 Constriction of smooth m. via V1 receptor IP3/Ca++ mechanism
 Mesenteric a.
o Mechanism:
 A lot of free water is re-uptaken  urine will be concentrated  tubular fluid will have
higher fluid osmolarity than plasma fluid
 TF can reach 1200 mOsm
 Increase water intake = TF osmolarity will be very dilute & plasma osmolarity will be
around normal 280-284 mOsm
o Syndrome of Inappropriate ADH (SIADH)
 Plasma osmolarity of 260-270 mOsm
 Urine osmolarity of 550 mOsm  concentrating the urine
 Dx:
 ADH related peptide tumor (lung cancer)
 Shouldn’t be concentrating the urine w/low plasma osmolarity of only 270
mOsm
 Low BUN, albumin
 No edema or increase in total body water
o Other Actions of ADH
 Increases mesangial cell contraction


Lowers filtration coefficient of glomerular membrane & thus decreases GFR &
decreases amount filtered by kidney
 In anterior pituitary (via V1 receptor –IP3), ADH can increase ACTH secretion 
Cortisol increased
o Q. Why does alcohol dehydrate you?
 Blocks ADH release
o Disturbances in ADH Regulating Water Balance
 Central diabetes insipidus or Neurogenic DI
 Lack ADH secretion b/c defect in hypothalamus
 Can replace ADH to txt
 Dx:
o Higher than plasma 290 mOsm
o Lower urine osmolarity (not concentrating the urine)
o Water restriction makes WORSE
 Nephrogenic DI
 Resistance to actions of ADH
 CAN’T replace ADH
 Psychogenic DI (primary polydipsia)
 Compulsive water drinker
 Low plasma & urine osmolarity
 Water restriction = txt
Oxytocin
o General Info:
 Oxytocin & ADH have some overlap w/biologic activity
 Only hormone w/true + feedback
o Mechanism:
 Stimulates contraction of uterine myometrium
 Release of OT is a neurohormonal reflex initiated by stretch of the cervix
 Natural labor inducer = UNKNOWN
 OT receptors expressed toward end of pregnancy, so if Ptocin is given during 5 mo of
pregnancy, no contractions will occur
 Causes contraction of breast  milk let down
 Doesn’t produce milk!
Cell Bio Lecture 19 and 20: Adrenal Cortex
 Secretes “GFR” or “the deeper you go, the sweeter it gets”
o Glomerulosa  aldosterone (mineralcorticoids)
 Aldosterons retains Na+
 ALWAYS NECESSARY FOR LIFE
 W/out aldosterone, loss Na+, retain K+ (hyperkalemia  heart problems)
o Fasiculata  cortisol (glucocorticoids)
 Cortisol regulates glucose
 Needed for stress
o Reticularis  DHEA (androgens)
 DHEA regulates libido
 Not necessary for life, weak androgens
 All steroid hormones made from cholesterol
o CYP11A1 is enzyme that cleaves side chain
 Also called:
 Cholesterol side chain cleavage


 Cholesterol desmolase
 P450ssc
 This is the rate limiting step in hormone biosynthesis
 Cholesterol  Pregnenolone
 Pregnenolone doesn’t cause physiological change yet b/c hasn’t bound to a receptor
o General Info:
 Cortisol is negative feedback for ACTH production
 ACTH induces cholesterol desomolase ***the rate-limiting step in hormone production
 W/out cortisol, the other hormones will be produced in excess
 Steroids are synthesized de novo – never stored
 When steroids are bound, they have a longer half-life
 17-hydroxylase not in glomerulsoa layer, so only fasiculata & reticularis layers
can make cortisol
 STAR transports cholesterol into mitochondria
 ACTH activates STAR
Activities of Steroids
o Mineralocorticoids
 Aldosterone = most potent
 Deoxycorticosterone w/1/30 the activity of aldosterone
 Corticosterone w/slight activity
 9 alpha-flourcortisol = synthetic & MORE POTENT
 Cortisol = slight mineralcorticoid activity
o Glucocorticoids
 Cortsiol = most potent
 Corticosterone = slight activity
 Cortisone = nearly as potent as cortisol
 Prednisone = 4x as potent
 Methylprednisone = 5x
 Dexamethasone = 30x
Aldosterone
o Target: Kidney (same target as ADH) cortical collecting tubules/distal tubules
o Increase in ECF volume  increase in BP
o When Na+ is reabsorbed, it is partially exchanged for K+ and H+
o Increased expression of Na/K ATPase pump on serosal (plasma) membrane
o Fine tuning of Na+ for body osmolarity
o Lack of Mineralcorticoids
 Salt wasting  hypotension
 Hyperkalemia (K+ retention)
 Metabolic acidosis (H+ not excreted in urine)
o Excess Mineralcorticoids
 Salt retention  hypertension
 Hypokalemia
 Metabolic alkalosis (H+ is excreted in urine)
o Actions of Aldosterone
 Increase renal Na+ reabsorption in principal cells in distal tubule & CCD
 Increase renal K+ secretion
 Increase H+ secretion in intercalated cells (prevent acidosis)
o W/elevated aldosterone, aldosterone escape will occur & eventually lead to normal ECV &
thus normal mean arterial pressure
 Elevated aldosterone long-term
 However, K+ levels will continue to drop, and become very low

o Aldosterone levels increase w/:
 Angiotensin II (renin stimulated)
 Increase in plasma K+
 Increase in ACTH
o How Renin works to stimulate Aldosterone
 Low pressure or low Na+  renin  cleave angiotensinogen to angiotensin I 
angiotensin I to angiotensin II via ACE in lungs  angiotensin II binds receptors and
induces P450ssc (cholesterol desmolase) & aldosterone synthase in glomerulosa
 Angiotensin II also acts in hypothalamus to increase thirst and AVP (vasopressin/ADH)
 Mesangial cells also contract b/c of Ag II
o Mechanism of Aldosterone
 Bind receptor  induce Na/K ATPase transporter  more K+ in the cell  K+ to the
nephron  K+ excreted
 Also allows for Na/H exchanger to excrete H+ in urine to regulate and prevent
metabolic acidosis
o Counter-Regulatory Hormone = ANP
 Hypervolemia  sensed in atrium of heart  released ANP  ANP binds receptor in
zona glomerulosa  decrease aldosterone production
 ANP can also bind receptors in afferent arterioles in kidney  increase flow & GFR 
decrease reabsorption of Na+ and thus water
 Hypervolemia also sensed in juxaglomerular apparatus to decrease renin  decrease
angiotensin II  down regulating aldosterone
Mechanism of Steroid Formation
Cholesterol
Cholesterol desmolase
17a-hydroxylase
17hydroxyprenenolone
pregnenolone
3Bhydroxysteroid
dehydrogenase
17,20-lyase
17androgesterodione
hydroxyprogesterone
progesterone
21B-hydroxylase
11deoxycorticosterone
11-deoxycortisol
11B-hydroxylase
Aldosterone
synthase
aldosterone
DHEA
3B-hyroxysteroid
dehydrogenase
17a-hydroxylase
corticosterone
17,20-lyase
Cortisol
Disorder:
Addison’s Disease
(primary adrenal
insufficiency)
Cushing’s Syndrome
(primary adrenal
hyperplasia)
Cushing’s Disease
AP-problem-ACTH
(secondary
hypercortisolism)
Conn’s Syndrome
Aldosterone tumor
(primary adrenal
hyperaldosteronism)
21B OHase defect adrenogenital
syndrome (90% will
have this defect)
Feature:
Hypoglycemia, hyperkalemia,
metabolic acidosis,
hyperpigmentation
m. wasting, female virilization
(maybe), central obesity, striae,
hyperglycemia, HTN
ACTH
Increased
Decreased (pt is in
cortisol excess &
cortisol is negative
feedback for
ACTH)
Increased (ACTH
secreting tumor)
Txt
Glucocorticoids
and/or
mineralcorticoids
Ketoconazole,
Metyrapone
Same as Cushing’s Syndrome,
Removal of ACTH
MSH will be elevated (darker
tumor
skin), cortisol elevated (ACTH
high), hyperglycemia
High Na+, HTN, hypokalemia,
No affected by
metabolic alkalosis (H+
increased
excreted), plasma renin low b/c aldosterone
plenty of aldosterone & HTN
Virilization, symptoms of
Increased (b/c no
Replacement of
glucocorticoid/mineralcorticoid cortisol)
glucocorticoids &
loss, Na+ loss (salt wasting) 
aldosterone
hypotensive, K+ retention
(hyperkalemia), H+ retention
(metabolic acidosis). NO
Cortisol  hypoglycemic
11B OHase defect
Symptoms of mineralcorticoid
Increased
Replacement of
excess, glucocorticoid loss, high
glucocortiocoids
DHEA  virilization, 11-DOC
present (has some aldosterone
like activity)  Na+ retention
(HTN), K+ excretion
(hypokalemia), H+ excretion
(metabolic alkalosis). NO
cortisol  hypoglycemia
17 OHase defect
Symptoms of mineralcorticoid
Increased
Replacement of
excess, symptoms of
glucocorticoids &
glucocorticoid deficiency. NO
aldosterone
DHEA  NO VIRILIZIATION.
antagonist
Lots 11-DOC  Na+ retention
(aldosterone is
(HTN), K+ excretion
very high)
(hypokalemia), H+ excretion
(metabolic alkalosis), NO
cortisol  hypoglycemia
Q. With 17a-hydroxylase defect would aldosterone levels be high or low?
Levels of aldosterone would be low, because aldosterone synthase is regulated by angiotensin II.
Angiotensin II is elevated when hypotensive & with this defect, we are HTN b/c 11-DOC is elevated
which leads to elevated Na+ and thus HTN
Q. Adrenal secreting tumor, remove it, and the patient dies 4 days later. What happened?
Removed all the aldosterone (maintains Na+ concentration & secretes K+). Patient died of
hyponatremia or hyperkalemia
Q. 12 yo boy w/BP 160/98, low serum K+, pH 7.67 & eats licorice constantly.
Can act on kidney to increase effects of MC activity and aldosterone like effects
 3B-hydroxysteroid dehydrogenase defect
 Defect will not be compatible w/life
 Partial defect = won’t produce aldosterone or cortisol
 When DHEA is elevated, so will 17-ketone 19-carbon steroids in urine
 Regulation of ACTH Biosynthesis
o Cortisol peaks 8 am, ACTH peaks at 7-8 am  circadian
o CRH = most important mediator of ACTH produced
o Stress induces cortisol
 Cortisol Regulation
o CTH induced by:
 CRH
 Circadian rhythm
 Stress
o Cortisol is negative feedback to ACTH
 Dexamethasone Suppression Test
o Use: Determine defect w/elevated cortisol
o ACTH should go down if given dexamethasone
o Low-dose overnight method, measure at 8 am
 If ACTH is suppressed, we know feedback is working
 If ACTH is not suppressed, do high dose method
o High-dose overnight method
 If have higher set point of ACTH, the high-dose method should cause
suppression of ACTH
 If ACTH is no suppressed with this method, then ACTH secreting tumor
 POMC
o Prohormone of ACTH along w/other products
o Adrenal insufficiency, not producing cortisol, ACTH elevated, POMC also elevated
o POMC is also a prohormone to melanocyte stimulating hormone (MSH)  darker skin
 Biological Actions of Cortisol (Many)
o Anti-insulin (diabetogenic)
 Increase in serum glucose
o Cortisol permits maximum epinephrine & stimulation of lipolysis (mostly in
extremities)
o Reduce bone & connective tissue by inhibiting fibroblast proliferation & collagen
formation
 Cortisol decreases Ca++ reabsorption & intestinal Ca++ absorption
 Can lead to osteoporosis w/excess
o Vascular system – maintain BP:
 Increase myocardial performance
 Decrease production of vasodilator prostaglandins
o CNS effect – decrease REM sleep, can cause insomnia
o Fetal development facilitated by cortisol
 Produce lung surfactant
o Inflammatory & immune responses profoundly influenced by cortisol
Cell Bio Lecture 21 & 22: Adrenal Medulla
o Adrenal Medulla
o Blood flows from capsule to medulla and along the way picks up steroid hormones
o Fxn cells: chromaffin/pheochromocytes
 Loaded w/epinephrine, catecholamines
o Similar to postganglionic sympathetic neuron “fight or flight”
o If you lost your medulla, no real life-threatening effects
o Cortisol is 100x higher in medulla
 Important b/cortisol induces PMNT which converts norepi to epinephrine
 80% epi & 20% norepi
o Secretion & Circulating Catecholamine Levels
o Secretion increases by “emergency” conditions:
 Hypoglycemia
 Hypovolemia
 Hypotension
 Stress or pain
o Rapid (epi)
o Cortisol elevated 30-60 min later
o 4 stress hormones: GH, cortisol, epi, glucagon
o Actions of Catecholamine
o β1: Epinephrine > Norepinephrine
 Increase cardiac contractility (β1)
 Increase heart rate (β1)
o β2: only Epinephrine
 Increase m. relaxation (β2)
 Airway smooth muscle
 Vascular smooth muscle
 Uterine smooth muscle
 Increase arteriolar dilation: decrease BP (β2)
o α: Norepinephrine > Epinephrine
 Increase gluconeogenesis
o α1 receptors:
 Vascular & other smooth m. contraction
 Norepi & epi bind α1 receptors
o α2 receptors:
 Inhibitory, act via inhibitory G-protein  decrease cAMP (opposite effect from β
receptors on intracellular cAMP)
 Norepi & epi bind well to α2
o Heart
 Epinephrine effects on heart
 Epi alone lowers total peripheral resistance via vasodilatory effects
 Stimulates HR via β1
 β2 binding of epi will cause vasodilation, keeping HR pumping
 Increases BP
 Increases CO
 Norepinephrine effects on heart
 Norepi increases total peripheral resistance via α1  causing reflex
bradycardia
 Decreases HR b/c only acts through α1 and β1
 Decreased CO
 Increased BP
o Overall Effects of Norepi/Epi
 Insulin resistance, increasing plasma glucose to supply CNS & for alternate fuels
 Still have glucose to m. b/c m. cells are insulin independent
o Overall Actions of Norepi/Epi
 BMR can increase 7-15% w/epi or Norepi
 Epi stimulates lipolysis via β-activation
 Increase renin release from kidney
 Increase TH secretion & conversion of T4  T3
 Increase β-receptor production, particularly heart
 Greater uterine contractions
o General Info:
o Epi contributes to glucose homeostastis, but is only critical when glucagon absent
o Epi increases by: standing up, exercise, hypoglycemia, smoking
o Most circulating Norepi is derived from “escaped” synaptic NE, NOT MEDULLA
o Half life is very short (1-3 min)
o Most metabolized via COMT & combo of monoamine oxidase & aldehyde oxidase
o Disorders:
o Neuroblastoma = MOST COMMON EXTRACRANIAL SOLID CANCER IN KIDS
 < 2 yo
 Neuroendocrine tumor
 Most frequently originates in adrenal glands
o Pheochromocytoma
 Q. You suspect pheochromocytoma, what do you do?
 24 hr UA
o epi & norepi are met. Quickly & secreted in urine
o VMA test and VMA ratio to metanephrines
 Pure VMA, look at normetephrine = norepi secreting tumor
 VMA ratio to metanephrines = epi secreting tumor
 Q. In a pheochromocytoma, if the prednominat-secreted hormone is
epinephrine, the tumor is most likely where & due to what enzyme?
 Medulla, PMNT is elevated
 Clinical: hot flashes, racing heart, increase BP, adrenal mass
 Usually transient-except for mass
o Epinephrine in Excess
 Increased BP, reflex slowing of HR
 Chronic effect:
 Increased BMR
 Weight loss
 Hyperglycemia
 Dx: NE & E at rest, VMA, metanephrine
 Txt: α-antangoist for BP, β-antagonist for bradycardia
 Definitive = surgical removal of tumor
Cell Bio Lecture 23: Prostaglandins, Eicosanoids, Thromboxanes
o Arachidonic acid is precursor to prostaglandins (PG), thromboxanes (TX), leukotrienes (LT)
o Very short half-life
o Locally acting
o More potent against COX-1 than COX-2
o Sits in membrane until changed to PG, TX, LT
o Corticosteroids (Cortisol, Prednisone, Hydrocortisone) inhibit phospholipase A2
 The 1st step that releases arachidonic acid
 The anti-inflammatory effect
o Thromboxanes (TXA2)
o Produced by platelets (thrombocytes)
o Actions:
 Vasoconstriction
 Increase platelet aggregation & clot formation
o NSAIDs will block this via COX activation
o Prostacyclin (PGI2)
o Produced by vascular endothelial cells
o Actions:
 Inhibit platelet aggregation
 Potent vasodilator used in Raynaud’s, ischemia in limb, & pulm. HTN
o Low dose Aspirin will not affect, but high doses will
o Leukotrienes (LT)
o Produced by leukocytes (WBC)
o LTB4 increases:
 Vascular permeability
 T-cell proliferation
 Leukocyte aggregation
 IFN-y
 IL-1 & IL-2
o LTC4, D4 increases:
 Bronchial constriction (asthma)
 Vascular permeability
 IFN-y
o NSAIDs – can cause GI bleeds b/c inhibits COX-1
o COX-1
 Produces PGE2 (vasodilatory) binds in stomach & decreases gastric acid secretion and
increases gastric mucus secretion (protection)
 COX-1 inhibitor = more acid, less mucus, more GI bleeds
o COX-2 inhibitors
 Reduces risk of peptic ulceration
 COX-2 inhibitors increases risk of atherothrombosis w/2 fold increased risk of MI
 Adverse effect, also possible increased risk of renal failure
o Baby aspirin (acetylsalicylic acid)
o Irreversibly blocks COX activation of platelet for life of platelet
Cell Bio Lecture 24 & 25: Calcium
Disorder
PTH
Serum Ca++
Serum PO4Primary
Increased
Increased
Decreased
Hyperparathyroidism
Primary
Decreased
Decreased
Increased
Hypoparathyroidism
(usually from thyroid
removal)
Renal Failure (similar to Increased
Decreased
Increased
primary
hypoparathyroidism)
Secondary
Increased
Decreased (this is the
Decreased
hyperparathyroidism
cause)
(caused by decrease in
plasma Ca++-Vit D
deficiency)
Secondary
Decreased
Increased (too much
Increased
Hypoparathyroidism
absorption of Ca++)
(increase in plasma Ca++
too much Vit D)
o Vitamin D toxicity causes both elevated plasma Ca++ and elevated plasma phosphate
o This is due to increased Ca++ and Vit. D shutting off PTH secretion (which normally would
increased phosphate loss in urine)
o Lack of Vitamin D causes rickets  growth failure & limb deformities in kids
o Osteomalacia (softening of bones) occurs in adults
o Define: loss of mineralization of the bone matrix collagen, w/out actual loss of the matrix
o Free calcium is regulated mainly by PTH which acts to raise Ca++ by both fast and slow actions
o Fast actions of PTH include increased Ca++ reabsorption in the kidney, inhibition of phosphate and
transfer of free calcium from the interstitial fluid surrounding the bone
o Calcitonin lower plasma calcium by decreasing activity of osteoclasts
o In primary parathyroidism, plasma Ca++ and phosphate change in opposite direction but they
change in the same direction in secondary disorders
o Main circulating form of vitamin D is 25-OH form, but actual physiologic form is 1,25 OH
o Normally, vitamin D promotes bone deposition b/c it increases the plasma levels of both Ca++ and
phosphate
o Vitamin D deficiency is an example of a secondary hyperparathyroidism
o Calcium
o Plays crucial roles in m. contraction, nerve function, and blood coagulation
o Normal levels: 8.5 to 10.5 mg/dl
o Decreased Calcium  increased neuromuscular excitability, tetany, laryngeal spasms,
asphysiation
o Increased Calcium  decreased neuromuscular excitability, bone pain, lethargy, anorexia,
muscle weakness, constipation, calcium stones (stones, bones, and groans)
o Phosphate
o Hyperphosphatemia leads to increased binding of free Ca and thus  decreased free Ca
o PTH
o Negative regulator of PTH is plasma free Calcium
o PTH is tonically inhibited by Calcium
o Major control mechanism of calcium homeostasis
o PTH secreted in response to decreased plasma Ca++ levels
o Excess activity of parathyroid gland causes rapid reabsorption of calcium salts from the bones,
with resultant hypercalcemia in the ECF
o Hypofunction of the parathyroid gland causes hypocalcemia  tetany
o Acts to increase calcium reabsorption in distal tubule but decrease PO4 reabsorption in
proximal tubule
o Vitamin D
o Activated by:
 Low plasma free Ca++
 Low plasma PO4 High PTH
 Low 1,25-OH-D3
o Calcitonin
o Has opposite effect of PTH
o It lowers plasma calcium
o Secreted from thyroid C-cells begins when plasma calcium levels are above 9.5
o Target cell of calcitonin is: osteoclast