Regulation of Calcium and Phosphate Homeostasis II

Question 1

E2 and the anabolic androgens (testosterone and dihydrotestosterone) stimulate bone growth and increase and/or maintain

Answer 1

Bone density

Question 2

Exerts a number of effects that collectively affect Ca2+ and PO4 homeostasis to maintain bone density

Answer 2

Estrogen

Question 3

Stimulates the expression of VDR in the duodenum and may also directly increase Ca2+ absorption

Answer 3

E2

Question 4

What is the predominant ER receptor in humans?

Answer 4

ER-alpha

Question 5

Estrogen receptors are expressed by

Answer 5

Growth plate chondrocytes

Question 6

Acts in a biphasic manner to first stimulate longitudinal bone growth, but then over time induces epiphyseal closure, thus terminating longitudinal growth

Answer 6

ER

Question 7

In osteocytes, E2 blocks apoptosis and stimulates the secretion of

Answer 7

TGFB

Question 8

Blocks osteoclast differentiation

Answer 8

TGFB

Question 9

Impairs osteoclast differentiation and RANKL synthesis

Answer 9

Estrogen

Question 10

Which three things does estrogen promote in bones?

Answer 10

1. ) Osteoclast apoptosis
2. ) Osteoblast proliferation
3. ) Osteoprotegerin production

Question 11

Collectively, these actions support the maintenance of bone density by thwarting

Answer 11

Osteoclast-mediated reabsorption

Question 12

Is by and large sequestered to the epiphyseal chondrocytes, growth plate cartilage, osteocytes, and osteoblasts

Answer 12

Androgen Receptor (AR) expression

Question 13

Men with total E2 deficiency due to mutations in either ERa or CYP19 exhibit severe

-Despite normal testosterone levels

Answer 13

Osteopenia

Question 14

Thus, we may not receive a direct effect on bone growth from

Answer 14

AR expression

Question 15

Aromatase, i.e. the enzyme which aromatizes testosterone into E2

Answer 15

CYP19

Question 16

We can treat these men with osteopenia in order to induce epiphyseal closure and longitudinal bone growth by giving them

Answer 16

Exogenous Estrogen

Question 17

Since the predominant circulating anabolic androgen, testosterone, can be aromatized into E2 by a variety of tissues, the anabolic effects of androgens in bone are possibly due to

Answer 17

E2

Question 18

The best indicator of fracture risk in aging men

Answer 18

E2

Question 19

21-carbon steroids produced by the adrenal cortex

-produced in zona fasciculata and zona reticularis

Answer 19

Glucocorticoids

Question 20

In the context of bone, function to enhance reabsorption

Answer 20

Glucocorticoids

Question 21

Thus, prolonged glucocorticoid excess can result in

Answer 21

Glucocorticoid-induced osteoporosis

Question 22

Glucocorticoid-induced osteoporosis can lead to the development of

Answer 22

Osteonecrosis

Question 23

The rapid focal deterioration of bone, often occuring within the femoral head

Answer 23

Osteonecrosis

Question 24

Has complex effects in bone, involving both direct (via effects within osteoblasts, osteoclasts, and osteocytes), as well as indirect mechanisms within the kidneys and the small intestine where Ca2+ reabsorption and absorption, respectively, are impaired

Answer 24

Glucocorticoids

Question 25

Impede skeletal muscle function by increasing catabolism

Answer 25

Glucocorticoids

Question 26

Muscle wasting and the deleterious effects within bone can be exacerbated by the inhibitory effect of glucocorticoids on

Answer 26

Gonadal estrogen and androgen production

Question 27

Osteoblasts, osteoclasts, and osteocytes all express

Answer 27

Glucocorticoid receptors

Question 28

Within osteoblasts and osteocytes, glucocorticoids upregulate

Answer 28

Apoptosis

Question 29

Actually extend the life of osteoclasts

Answer 29

Glucocorticoids

Question 30

The production of RANKL is promoted by

Answer 30

Glucocorticoids

Question 31

The production of RANKL is promoted by glucocorticoids, thereby increasing the ratio of RANKL:osteoprotegerin; a mechanism that promotes

Answer 31

Osteoclast-mediated bone reabsorption

Question 32

Predominantly synthesized by the liver in response to GH

Answer 32

IGF-I

Question 33

However, it has been shown that IGF-I is also synthesized in

Answer 33

Osteocytes and chondrocytes

Question 34

Postnatally and through adolescence, GH and IGF-1 together stimulate

Answer 34

Longitudinal bone growth

Question 35

In long bones, exerts mitogenic effects in chondrocytes within the epiphyseal cartilages (epiphyseal lengthening) concomitant with stimulating local IGF-1 expression

Answer 35

GH

Question 36

Due to their anabolic effects, GH and IGF-I can also regulate modeling and remodeling of

Answer 36

Trabecular and cortical bone

Question 37

Note that the anabolic effects of GH depend on

Answer 37

IGF-I

Question 38

Osteoblast activity is upregulated by

Answer 38

GH

Question 39

GH promotes osteoblasts to express

Answer 39

IGF-I

Question 40

The expression of IGF-I in osteoblasts is also stimulated by

Answer 40

PTH and E2

Question 41

IGF-I expression is reduced by

Answer 41

Glucocorticoids

Question 42

In children, hypothyroidism is associated with

Answer 42

Blunted growth

Question 43

Has been shown to increase the activity of both osteoblasts and osteoclasts

Answer 43

Thyroid Hormone

Question 44

In adult hyperthyroidism, an upregulation in bone mineralization is in fact linked with increased

Answer 44

Reabsorption

Question 45

A wasting of the bone matrix that is associated with the age dependent drop in E2, and perhaps androgen, production that occurs in older men and women

Answer 45

Osteoporosis

Question 46

In women, the loss of ovarian function that defines menopause results in a profound decline in bioavailable

Answer 46

E2

Question 47

The hallmark sign of osteoporosis is the demineralization of bone leading to decreased bone density in the

Answer 47

Spine, hip, pelvis, and/or wrist

Question 48

Serum Ca2+, PO4, and PTH generally remain normal in

Answer 48

Osteoporosis

Question 49

Increases bone mineral density and thus exerts anti-osteoporotic effects in properly nourished post menopausal women

Answer 49

Estrogen Replacement Therapy (ERT)

Question 50

Commonly prescribed for osteoporosis

Answer 50

Bisphosphonates

Question 51

Act to prevent bone absorption by impairing osteoclast activity and accelerating osteoclast apoptosis

Answer 51

Bisphosphonates

Question 52

Another treatment treatment for osteoporosis is

Answer 52

Selective Estrogen Receptor Modulators (SERM)

Question 53

A SERM which functions as an E2 agonist in bone, while antagonizing E2 in breast and uterine tissue

Answer 53

Raloxiphene

Question 54

A human monoclonal antibody against RANKL that is used to treat osteoporosis

Answer 54

Denosumab

Question 55

The third most common endocrine disorder

Answer 55

Primary hyperparathyroidism

Question 56

Approximately 75-80% of the time, results from a single parathyroid adenoma causing hypersecretion of PTH from parathyroid glands

Answer 56

Primary hyperparathyroidism

Question 57

Elevated PTH results in

Answer 57

Hypercalcemia

Question 58

In severe cases of hyperparathyroidism, we see loss of cortical bone and deposition of

Answer 58

Trabecular bone

Question 59

The chief complaint in symptomatic hyperparathyroid patients is usually bone pain and

Answer 59

Arthralgias

Question 60

More frequent in those over 50 years of age and is 3x more common in women

Answer 60

Hyperparathyroidism

Question 61

If present, symptoms from pathologic hypercalcemia only appear at serum levels greater than

Answer 61

12 mg/dL

Question 62

In an electrocardiogram, hypercalcemia will show as a

Answer 62

Shortened QT

Question 63

During phase 2 depolarization (i.e. the plateau phase; of the cardiac myocyte action potential, calcium slowly enters the cell. The duration of phase 2 is directly correlated with the duration of the

Answer 63

ST segment

Question 64

When the extracellular Ca2+ levels are elevated, the Type L channels become -activate and inactivate more frequently

Answer 64

Irritated

Question 65

Although rare with hypercalcemia, disruption of cardiac electrical activity can lead to serious

Answer 65

Arrythmias

Question 66

With regard to skeletal muscle, experimental evidence has shown that excess extracellular Ca2+ raises the membrane potential necessary to open the motor neuron voltage-gated Na+ channels, thus inducing

Answer 66

Hypoexciteability

Question 67

Patients with hypercalcemia due to primary hyperparathyroidism have increased renal excretion of

Answer 67

Ca2+ and PO4

Question 68

The hypercalciuria predisposes the formation of

Answer 68

Kidney stones

Question 69

Also, the abnormal increase in Ca2+ concentration within the forming urine can induce aberrant CaSR activity which can lead to a form of

Answer 69

Ca2+ Dependent nephrogenic diabetes insipidus

Question 70

The most common cause of true hypocalcemia is the loss of calcitriol synthesis that results from the advanced stages of

Answer 70

Chronic kidney disease

Question 71

Signs and symptoms of this condition are associated with the increase in nerve and muscle excitability that accompanies

Answer 71

Hypocalcemia

Question 72

It appears that extracellular Ca2+ aids in somehow stabilizing membrane Na+ channels within

Answer 72

Skeletal muscle and neurons

Question 73

With low extracellular Ca2+, membrane permeability to Na+ is increased and the result is

Answer 73

Hyperexciteability

Question 74

If severe enough, hypocalcemia can impair ventricular conductivity and ventricular myocyte contractility and is shown on an ECG as

Answer 74

Prolonged QT interval

Question 75

Skeletal muscle cramping and/or tetany, and perioral and distal extremity paresthesias can occur with

Answer 75

Hypocalcemia

Question 76

There are two signs that can be used in the diagnosis of hypocalcemia. The first is

Answer 76

Trousseau's sign

Question 77

Shows as a carpal spasm due to the loss in brachial artery circulation that occurs upon inflation of a BP cuff above systolic BP

Answer 77

Trousseau's sign

Question 78

Approximately what percent of patients with hypocalcemia will show Trousseau's sign?

Answer 78

94%

Question 79

The second test for hypocalcemia is known as

Answer 79

Chvostek's sign

Question 80

This is observed as ipsilateral facial muscle contraction when the facial nerve is tapped anterior to the ear

Answer 80

Chvostek's sign

Question 81

Which test has a higher specificity, Trousseau's or Chvostek's?

Answer 81

Trousseau's

Question 82

Hyperphosphatemia is indicated by serum PO4 above

Answer 82

5mg/dL

Question 83

Most often due to acute and chronic renal failure, when GFR falls under 30 mL/min

Answer 83

Hyperphosphatemia

Question 84

Abnormally elevated PO4 tends to precipitate

Answer 84

Ca2+

Question 85

Tends to precipitate Ca2+, impairs calcitriol synthesis, and impedes PTH mediated bone resorption

Answer 85

Abnormally elevated PO4

Question 86

Thus, the signs and symptoms of hyperphosphatemia are actually attributed to the ensuing

Answer 86

Hypocalcemia

Question 87

If prolonged, hyperphosphatemia and the associated Ca2+ imbalances can progress to the formation of metastatic calcifications which tend to develop within the vascular walls, ventricular myocardium, as well as

Answer 87

Atrial and mitral valves

Question 88

The most common etiology of hypophosphatemia is due to an increase in PO4 excretion that accompanies

Answer 88

Hyperparathyroidism

Question 89

During severe hypophosphatemia (≤1 mg/dl), the affinity of hemoglobin for O2 is increased due to a decrease in

Answer 89

2,3 DPG

Question 90

Since O2 cannot be effectively offloaded to tissues, | skeletal muscle cell weakness and sometimes skeletal muscle necrosis can occur. This necrosis is also known as

Answer 90

Rhabdomyolysis

Question 91

A condition of childhood calcitriol deficiency or resistance prior to epiphyseal plate closure

Answer 91

Rickets

Question 92

The adult form of Rickets is called

Answer 92

Osteomalacia

Question 93

The calcitriol deficiency induces increased PTH-dependent elimination of PO4 in the urine, and the inability to absorb

Answer 93

Dietary Ca2+

Question 94

SIgns and symptoms of Rickets/osteomalacia would then include bone pain and tenderness, diminished bone density/mineralization, as well as

Answer 94

Hypophosphatemia, hypocalcemia, and hypocalciuria

Question 95

If this condition is not corrected, we can see severe bone weakening and

Answer 95

Tetanic respiratory failure