2-4-16-Regulation Of Ca And PO4 Metabolism (Lopez) Flashcards
___ is twitching of the facial muscles elicited by tapping on facial n.
Chvostek sign
___ is carpopedal spasm upon inflation of a BP cuff
Trousseau sign
__ is characterized by a decreased QT interval, constipation, lack of appetite, polyuria, polydipsia, muscle weakness, hyporeflexia, lethargy, and coma
Hypercalcemia
___ reduces the activation threshold for Na channels –> easier to evoke an AP (less or no stimulus required to trigger an AP). THis results in increased membrane excitability and can produce numbness and tingling and muscle twitches
Hypocalcemia –> generation of spontaneous AP is the physical basis for hypocalcemic tetany
___ is characterized by decreased membrane excitability and the NS becomes depressed and reflex responses are slowed
Hypercalcemia
During ___, free ionized [Ca] increases because less Ca is bound to albumin
Acidemia –> leads to increased free ionized [Ca]; H+ kicks off the Ca2+ from albumin
During ___, free ionized [Ca] decreases, often accompanied by hypocalcemia
Alkalemia –> decreased ionized [Ca]; Ca stays on albumin since H+ does not displace it
Ca homeostasis is tightly regulated by these 3 organs ___ and these 3 hormones ___
Bones, kidneys, and intestine
PTH, calcitonin, Vit D
___ is an intracellular anion involved in the activation and deactivation of enzymes, as well as a buffer in bone, serum, and urine
PO4–> bone (85%), Plasma (
EC [Pi] is __ related to that of [Ca]
Inversely
The __ cells of the parathyroid glands synthesize and secrete PTH
Chief
What is the main stimulus for secretion of PTH?
Decreased plasma [Ca]
___ is characterized by long-term increased levels of plasma [Ca] and causes decreased synthesis and storage of PTH, increased breakdown of stored PTH and release of inactive PTH fragments into circulation
Chronic hypercalcemia
___ is characterized by long-term decreased plasma [Ca] and causes increased synthesis and storage of PTH, and hyperplasia of parathyroid glands (secondary hyperparathyroidism)
Chronic hypocalcemia
Severe hypomagnesemia can cause what?
Inhibition of PTH synthesis, storage, and secretion –> result of chronic Mg2+ depletion, as in alcoholism
PTH acts via this secondary messenger system___
Adenylate cyclase/cAMP
List the physiological affects of PTH on:
A-bone
B-Kidney
C-Intestine
A-Increased bone resorption
B-Decreased Pi reabsorption (phosphaturia), increased Ca reabsorption, increased urinary cAMP
C-Increased Ca reabsorption (via Vit D)
All will increase plasma [Ca] toward normal
__ promotes mineralization of new bone through its coordinated actions in the regulation of both Ca and Pi plasma concentrations
Vitamin D –> “steroid” hormone
In vitamin D synthesis, 7-dehydrocholesterol is converted to cholecalciferol via UV light. Cholecalciferol is then converted to 25-OH-cholecalciferol in the liver by this enzyme ___
25-hydroxylase
25-OH-cholecalciferol is converted to 1,25-(OH)2-cholecalciferol in the renal PCT by this enzyme ___
1-alpha-hydroxylase (CYP1alpha)
PTH receptors are located on these cells ___
Osteoblasts (not osteoclasts)
What are the short-term actions of PTH on bone?
What are the long-term actions of PTH on bone?
Short-term: Bone formation (via direct action on osteoblast) –> basis for use of intermittent synthetic PTH administration in osteoporosis treatment
Long-term: Increase bone resorption (indirect action on osteoclasts mediated by cytokines released from osteoblast)
___ acts synergistically with PTH to stimulate osteoclast activity and bone resorption
Vitamin D
In the formation and resorption in bone, ___ induces stem cells to differentiate into osteoclast precursors, mononuclear osteoclasts, and finally as mature multinucleated osteoclasts
M-CSF
___ is a cell surface protein produced by osteoblasts, bone lining cells, and apoptotic osteocytes. It is the primary mediator of osteoclast formation
RANKL (Receptor activator for NF-kB ligand)
___ is a cell surface protein receptor on osteoclasts and osteoclast precursors
RANK
___ is a soluble protein produced by osteoblasts, a decoy receptor for RANKL, inhibitor of RANK/RANKL interaction
Osteoprotegerin
Osteoclast formation can occur via this ligand-receptor interaction ____
RANKL-RANK
Osteoprotegerin inhibits
___ increases RANKL and decreased osteoprotegerin
___ increases RANKL
PTH
Vit D
List the MOA of PTH on the kidney, specifically cells of the PCT
PTH binds its receptor on the basolateral membrane –> stimulates a Gs-Adenylate cyclase-cAMP 2nd messenger system –> activates protein kinase –>Phosphorylation–> inhibits Na-PO4 co-transporter to reabsorb both from the lumen (apical membrane)
Inhibition of the Na-PO4 co-transporter on the apical membrane (lumen side) of the cells of the PCT causes ___
Phosphatria (increased excretion of Pi in urine)
What are the actions of Vit D on the kidney?
Stimulates both Ca and Pi reabsorption
In the SI, vitamin D increases Ca and Pi absorption by increasing ___ expression
Calbindin
In the parathyroid gland, Vitamin D directly inhibits ___ expression and directly stimulates ___ expression
PTH gene
CaSR gene
___ decreases blood Ca and Pi concentrations by inhibiting bone resorption. It decreases the activity and number of osteoclasts
Calcitonin –> major stimulus=increased plasma [Ca]
A thyroidectomy will have what effect on calcitonin and Ca metabolism?
A thyroid tumor will have what effect on calcitonin and Ca metabolism?
Thyroidectomy –> decreased calcitonin, no effect on Ca metabolsim
Thyroid tumor –> increased calcitonin, no effect on Ca metabolism
____ stimulates intestinal Ca absorption and renal tubular Ca reabsorption. It is also one of the most potent regulators of osteoblast and osteoclast function (promotes survival of osteoblasts and apoptosis of osteoclasts which favors bone formation)
Estradiol-17b
___ promote bone resorption and renal Ca wasting and inhibit intestinal Ca absorption
Adrenal glucocorticoids (cortisol)
In this disorder, pts excrete excessive amounts of Pi, cAMP, and Ca (Ca-oxalate stones).
Primary hyperparathyroidism –> “stone” “bones” and “groans” ; hypercalciuria (stones), increased bone resorption (bones), constipation (groans)
What is a possible tx for primary hyperparathyroidism?
Parathyroidectomy
List levels of PTH, Ca, Pi, and Vit D in primary hyperparathyroidism:
PTH=increased
Ca=Increased
Pi=Decreased
Vit D=Increased
___ is characterized by increased PTH levels secondary to low [Ca] in blood. The low [Ca] can be caused by renal failure and vit D deficiency
Secondary hyperparathyroidism
List levels of PTH, Ca, Pi, and Vit D in secondary hyperparathyroidism due to Renal failure
PTH=increased
Ca=decreased
Pi=Increased
Vit D=decreased
List levels of PTH, Ca, Pi, and Vit D in secondary hyperparathyroidism due to Vit D deficiency
PTH=Increased
Ca, Pi, Vit D=all decreased
___ can be caused by thyroid and/or parathyroid surgery or can be autoimmune. Most symptoms are associated with decreased Ca which can lead to muscle spasm or cramping, seizures, numbness, tingling, or burning
Hypoparathyroidism –> tx with oral Ca supplement and active form of Vit D
List levels of PTH, Ca, Pi, and Vit D in Hypoparathyroidism
PTH=decreased
Ca=Decreased
Pi=Increased
Vit D=decreased
__ is an inherited autosomal dominant disorder with a defect in Gs protein for both PTH in bone and the kidneys are defective. This leads to development of hypocalcemia and hyperphosphatemia. Phenotype includes short stature, short neck, obesity
Albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)
List levels of PTH, Ca, Pi, and vit D for Albright hereditary Osteodystrophy (pseudohypoparathyroidism type 1a)
PTH=increased
Ca=Decreased
Pi=increased
Vit D=decreased
What are some symptoms of hyperparathyroidism?
Kidney stones Osteoporosis GI disturbances Muscle weakness, Depression Polyuria High serum [Ca], low serum [PO4]
What are some symptoms of hypoparathyroidism?
Tetany, convulsions, parasthesias, muscle cramps Decreased myocardial contractility 1st degree heart block CNS problems-irritability and psychosis Intestinal malabsorption Low serum [Ca]; high serum [PO4]
___ is a disorder characterized by increased PTHrP levels and produces a similar profile to primary hyperparathyroidism such as increased urinary Ca, increased urinary Pi, cAmp as well as increased blood Ca and decreased blood Pi
Humoral hypercalcemia of malignancy
___ is a peptide produced by tumors with close homology in the N-terminal to PTH
PTHrP –> binds and activates same receptor as PTH
What is a tx for humoral hypercalcemia of malignancy?
Furosemide –> inhibits renal Ca reabsorption and increases Ca excretion
Etidronate –> inhibitor bone resorption
List levels of PTH, Ca, Pi, and Vit D for humoral hypercalcemia of malignancy
PTH=decreased
Ca=Increased
Pi=decreased
Vit D=decreased
__ is an autosomal dominant disorder caused by a mutation that inactivates CaSR in parathyroid glands and parallel Ca receptors in the ascending limb of the kidney. It results in decreased urinary Ca excretion (hypocalciuria) and increased serum [Ca] (hypercalcemia)
Familial Hypocalciuric Hypercalcemia (FHH)
List PTH, Serum Ca, Urine Ca, Pi, and Vit levels for FHH
PTH=increased Serum Ca=increased Urine Ca=decreased Pi=N Vit D=N
___ occurs when there is an insufficient amount of Ca and Pi available to mineralize growing bone and characterized by growth failure and skeletal deformities. Most common in children
Rickets
__ is when new bones fail to mineralize and characterized by bending and softening of weight-bearing bones
Osteomalacia
List the deficit in Pseudovitamin D-deficient Rickets of Vitamin D-dependent rickets Type 1
List the deficity in Pseudovitamin D-deficient Rickets or Vitamin D-dependent Rickets Type 2
Type 1–> decreased 1-alpha-hydroxylase
Type 2–> decreased vitamin D receptor
List PTH, Ca, Pi, urine, vit D levels and bone disturbances in the pathophysiology of Vitamin D
PTH=Increased (secondary) Ca=N/decreased Pi=decreased Urine=Increased Pi and increased cAMP Vit D=decreased (primary disturbance) Bone=osteomalacia, increased resorption
List treatments for osteoporosis
Antiresorptive therapy –> biphosphonates, estrogen, Selective estrogen receptor modulators, calcitonin, RANKL inhibitors (Denosumab)
Anabolic therapy –> PTH
__ is characterized by hyperreflexia, spontaneous twitching, muscle cramping, tingling and numbness, as well as + Chvostek sign and + Trousseau sign
Hypocalcemia –> decreased [Ca2+]
