2-4-16-Regulation Of Ca And PO4 Metabolism (Lopez)

Question 1

___ is twitching of the facial muscles elicited by tapping on facial n.

Answer 1

Chvostek sign

Question 2

___ is carpopedal spasm upon inflation of a BP cuff

Answer 2

Trousseau sign

Question 3

__ is characterized by a decreased QT interval, constipation, lack of appetite, polyuria, polydipsia, muscle weakness, hyporeflexia, lethargy, and coma

Answer 3

Hypercalcemia

Question 4

___ 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

Answer 4

Hypocalcemia –> generation of spontaneous AP is the physical basis for hypocalcemic tetany

Question 5

___ is characterized by decreased membrane excitability and the NS becomes depressed and reflex responses are slowed

Answer 5

Hypercalcemia

Question 6

During ___, free ionized [Ca] increases because less Ca is bound to albumin

Answer 6

Acidemia –> leads to increased free ionized [Ca]; H+ kicks off the Ca2+ from albumin

Question 7

During ___, free ionized [Ca] decreases, often accompanied by hypocalcemia

Answer 7

Alkalemia –> decreased ionized [Ca]; Ca stays on albumin since H+ does not displace it

Question 8

Ca homeostasis is tightly regulated by these 3 organs ___ and these 3 hormones ___

Answer 8

Bones, kidneys, and intestine

PTH, calcitonin, Vit D

Question 9

___ is an intracellular anion involved in the activation and deactivation of enzymes, as well as a buffer in bone, serum, and urine

Answer 9

PO4–> bone (85%), Plasma (

Question 10

EC [Pi] is __ related to that of [Ca]

Answer 10

Inversely

Question 11

The __ cells of the parathyroid glands synthesize and secrete PTH

Answer 11

Chief

Question 12

What is the main stimulus for secretion of PTH?

Answer 12

Decreased plasma [Ca]

Question 13

___ 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

Answer 13

Chronic hypercalcemia

Question 14

___ is characterized by long-term decreased plasma [Ca] and causes increased synthesis and storage of PTH, and hyperplasia of parathyroid glands (secondary hyperparathyroidism)

Answer 14

Chronic hypocalcemia

Question 15

Severe hypomagnesemia can cause what?

Answer 15

Inhibition of PTH synthesis, storage, and secretion –> result of chronic Mg2+ depletion, as in alcoholism

Question 16

PTH acts via this secondary messenger system___

Answer 16

Adenylate cyclase/cAMP

Question 17

List the physiological affects of PTH on:

A-bone
B-Kidney
C-Intestine

Answer 17

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

Question 18

__ promotes mineralization of new bone through its coordinated actions in the regulation of both Ca and Pi plasma concentrations

Answer 18

Vitamin D –> “steroid” hormone

Question 19

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 ___

Answer 19

25-hydroxylase

Question 20

25-OH-cholecalciferol is converted to 1,25-(OH)2-cholecalciferol in the renal PCT by this enzyme ___

Answer 20

1-alpha-hydroxylase (CYP1alpha)

Question 21

PTH receptors are located on these cells ___

Answer 21

Osteoblasts (not osteoclasts)

Question 22

What are the short-term actions of PTH on bone?

What are the long-term actions of PTH on bone?

Answer 22

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)

Question 23

___ acts synergistically with PTH to stimulate osteoclast activity and bone resorption

Answer 23

Vitamin D

Question 24

In the formation and resorption in bone, ___ induces stem cells to differentiate into osteoclast precursors, mononuclear osteoclasts, and finally as mature multinucleated osteoclasts

Answer 24

M-CSF

Question 25

___ is a cell surface protein produced by osteoblasts, bone lining cells, and apoptotic osteocytes. It is the primary mediator of osteoclast formation

Answer 25

RANKL (Receptor activator for NF-kB ligand)

Question 26

___ is a cell surface protein receptor on osteoclasts and osteoclast precursors

Answer 26

RANK

Question 27

___ is a soluble protein produced by osteoblasts, a decoy receptor for RANKL, inhibitor of RANK/RANKL interaction

Answer 27

Osteoprotegerin

Question 28

Osteoclast formation can occur via this ligand-receptor interaction ____

Answer 28

RANKL-RANK Osteoprotegerin inhibits

Question 29

___ increases RANKL and decreased osteoprotegerin ___ increases RANKL

Answer 29

PTH Vit D

Question 30

List the MOA of PTH on the kidney, specifically cells of the PCT

Answer 30

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)

Question 31

Inhibition of the Na-PO4 co-transporter on the apical membrane (lumen side) of the cells of the PCT causes ___

Answer 31

Phosphatria (increased excretion of Pi in urine)

Question 32

What are the actions of Vit D on the kidney?

Answer 32

Stimulates both Ca and Pi reabsorption

Question 33

In the SI, vitamin D increases Ca and Pi absorption by increasing ___ expression

Answer 33

Calbindin

Question 34

In the parathyroid gland, Vitamin D directly inhibits ___ expression and directly stimulates ___ expression

Answer 34

PTH gene CaSR gene

Question 35

___ decreases blood Ca and Pi concentrations by inhibiting bone resorption. It decreases the activity and number of osteoclasts

Answer 35

Calcitonin --> major stimulus=increased plasma [Ca]

Question 36

A thyroidectomy will have what effect on calcitonin and Ca metabolism? A thyroid tumor will have what effect on calcitonin and Ca metabolism?

Answer 36

Thyroidectomy --> decreased calcitonin, no effect on Ca metabolsim Thyroid tumor --> increased calcitonin, no effect on Ca metabolism

Question 37

____ 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)

Answer 37

Estradiol-17b

Question 38

___ promote bone resorption and renal Ca wasting and inhibit intestinal Ca absorption

Answer 38

Adrenal glucocorticoids (cortisol)

Question 39

In this disorder, pts excrete excessive amounts of Pi, cAMP, and Ca (Ca-oxalate stones).

Answer 39

Primary hyperparathyroidism --> "stone" "bones" and "groans" ; hypercalciuria (stones), increased bone resorption (bones), constipation (groans)

Question 40

What is a possible tx for primary hyperparathyroidism?

Answer 40

Parathyroidectomy

Question 41

List levels of PTH, Ca, Pi, and Vit D in primary hyperparathyroidism:

Answer 41

PTH=increased Ca=Increased Pi=Decreased Vit D=Increased

Question 42

___ 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

Answer 42

Secondary hyperparathyroidism

Question 43

List levels of PTH, Ca, Pi, and Vit D in secondary hyperparathyroidism due to Renal failure

Answer 43

PTH=increased Ca=decreased Pi=Increased Vit D=decreased

Question 44

List levels of PTH, Ca, Pi, and Vit D in secondary hyperparathyroidism due to Vit D deficiency

Answer 44

PTH=Increased | Ca, Pi, Vit D=all decreased

Question 45

___ 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

Answer 45

Hypoparathyroidism --> tx with oral Ca supplement and active form of Vit D

Question 46

List levels of PTH, Ca, Pi, and Vit D in Hypoparathyroidism

Answer 46

PTH=decreased Ca=Decreased Pi=Increased Vit D=decreased

Question 47

__ 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

Answer 47

Albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)

Question 48

List levels of PTH, Ca, Pi, and vit D for Albright hereditary Osteodystrophy (pseudohypoparathyroidism type 1a)

Answer 48

PTH=increased Ca=Decreased Pi=increased Vit D=decreased

Question 49

What are some symptoms of hyperparathyroidism?

Answer 49

``` Kidney stones Osteoporosis GI disturbances Muscle weakness, Depression Polyuria High serum [Ca], low serum [PO4] ```

Question 50

What are some symptoms of hypoparathyroidism?

Answer 50

``` 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] ```

Question 51

___ 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

Answer 51

Humoral hypercalcemia of malignancy

Question 52

___ is a peptide produced by tumors with close homology in the N-terminal to PTH

Answer 52

PTHrP --> binds and activates same receptor as PTH

Question 53

What is a tx for humoral hypercalcemia of malignancy?

Answer 53

Furosemide --> inhibits renal Ca reabsorption and increases Ca excretion Etidronate --> inhibitor bone resorption

Question 54

List levels of PTH, Ca, Pi, and Vit D for humoral hypercalcemia of malignancy

Answer 54

PTH=decreased Ca=Increased Pi=decreased Vit D=decreased

Question 55

__ 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)

Answer 55

Familial Hypocalciuric Hypercalcemia (FHH)

Question 56

List PTH, Serum Ca, Urine Ca, Pi, and Vit levels for FHH

Answer 56

``` PTH=increased Serum Ca=increased Urine Ca=decreased Pi=N Vit D=N ```

Question 57

___ 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

Answer 57

Rickets

Question 58

__ is when new bones fail to mineralize and characterized by bending and softening of weight-bearing bones

Answer 58

Osteomalacia

Question 59

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

Answer 59

Type 1--> decreased 1-alpha-hydroxylase Type 2--> decreased vitamin D receptor

Question 60

List PTH, Ca, Pi, urine, vit D levels and bone disturbances in the pathophysiology of Vitamin D

Answer 60

``` PTH=Increased (secondary) Ca=N/decreased Pi=decreased Urine=Increased Pi and increased cAMP Vit D=decreased (primary disturbance) Bone=osteomalacia, increased resorption ```

Question 61

List treatments for osteoporosis

Answer 61

Antiresorptive therapy --> biphosphonates, estrogen, Selective estrogen receptor modulators, calcitonin, RANKL inhibitors (Denosumab) Anabolic therapy --> PTH

Question 62

__ is characterized by hyperreflexia, spontaneous twitching, muscle cramping, tingling and numbness, as well as + Chvostek sign and + Trousseau sign

Answer 62

Hypocalcemia --> decreased [Ca2+]