Chem: Section 12- Bone

process in which bone is broken down within the body so it can be replaced by new bone; as bone is broken down, minerals such as calcium and phosphorous are released

bone resorption

What are PTH and calcitonin's effects on bone resorption?

PTH enhances

Calcitonin inhibits

process of forming bone; calcified matrix serves as site of deposition for minerals, which crystalize and develop into woven, compact bone

bone modeling

process that involves formation of bone on surfaces previously containing bone; two phases- breakdown by osteoclasts and rebuilding by osteoblasts

bone remodeling

Where is parathyroid hormone released?

parathyroid glands that are embedded in the thyroid

PTH is secreted in response to hypocalcemia and works to *increase* calcium in the blood. What are the 4 mechanisms of achieving this?

1) bone resorption

2) renal reabsorption

3) increased phosphate excretion

4) activation of vitamin D

What are the 3 forms of PTH that can be found in circulation? Which is the most abundant and active form?

intact PTH

*C-terminal fragments*

N-terminal fragments

How can PTH be measured? (4)

immunoassay, CAP assay, PTHrP assay, direct biopsy

Where is calcitonin secreted?

medullary "C" cells of the thyroid gland

Calcitonin is secreted in response to hypercalcemia and works to *decrease* calcium in the blood. What are the 3 mechanisms of achieving this?

1) inhibits the action of PTH and vitamin D

2) inhibits bone resorption and promotes bone deposition

3) enhances excretion of calcium in the urine

What are the 3 forms of calcium in the body, and which is the biologically active form?

*Free (ionized) calcium is the biologically active form*

Bound to plasma proteins (albumin and other globulins)

Forming complexes with a variety of anions (bicarb, lactate, phosphate, citrate)

What carrier protein is responsible for the majority of calcium binding?

albumin

How do protein levels affect calcium binding?

Need protein for carriers, so an increase in protein results in increased binding and a decrease in protein results in a decrease in binding (no protein to bind to)

How does pH affect calcium binding?

Proteins take on a negative charge when placed in an alkaline environment and calcium binds to negatively charged sited on proteins, so:

alkalosis= increased negative charges= increased binding (decreased free calcium)

acidosis= decreased negative charges= decreased binding (increased free calcium)

What organs are involved in calcium homeostasis?

*skeleton (primary reserve)*

*small intestine (absorption of Ca)*

*kidneys (convert calcidiol to calcitriol, can eliminate or retain Ca)*

skin

liver

parathyroid gland

What are the normal functions of calcium? (6)

muscle contraction, glycogen metabolism, hormone secretion, blood hemostasis (coag cascade), enzyme activation

What are some things that can cause hypercalcemia?

Primary hyperparathyroidism

Malignancy (tumors produce too much)

Sarcoidosis (autoimmune, granuloma)

Hypervitaminosis of vitamin D (ingesting too many vitamin D supplements)

Medications

What are some things that can cause hypocalcemia?

Hypoparathyroidism (from surgery or autoimmune e.g. diabetes Type I, hashimoto's, Addison's)

Pseudohypoparathyroidism (genetic disease associated with a lack of responsiveness to PTH in the target tissue; PTH itself is fine, but not responded to)

Vitamin D deficiency (from malnutrition, decreased exposure to UV light, malabsorption)

Renal-glomerular diseases, esp. Chronic renal failure

Acute pancreatitis

What are the S/S associated with hypercalcemia?

GI symptoms, neurologic changes, production of kidney stones, osteopenia/osteoporosis (too much PTH from a parathyroid tumor, breaks down too much bone trying to raise blood calcium)

What are some S/S associated with hypocalcemia?

tetany, spasms, convulsions, Chvostek sign (tap facial nerve, mouth and lip spasm), carpopedal spasm (hand stiffens in crooked position)

Why is vitamin D important to calcium homestasis?

vitamin D is broken down into calcidiol then *calcitriol* which increases calcium absorption from the intestines and promotes calcium reabsorption in the kidneys

What is the most common method for total calcium testing?

spectrophotometric (colorimetric endpoint)

What specimen must be used for calcium testing?

serum or heparinized plasma

CANNOT used EDTA because it binds calcium

What are some interferences to the measurement of total calcium?

lipemia and hemoglobin (turbidity), total protein (affects binding capacity)

How is free calcium (ionized) measured?

ISE with polyvinyl chloride (PVC) membrane

What are some interferences with ionized calcium measurement?

pH and temperature dependent, some anions can bind calcium away

What are the specimen handling requirements for the measurement of ionized calcium?

must be kept anaerobic, transported on ice, limit tourniquet use, exercise, hyperventilation, fist clenching

**all affect the pH

What is the function of phosphorus?

combines with lipids, proteins, carbohydrates, and other organic substances for a variety of roles, such as: phospholipids, nucleic acids, cellular components, energy storage and exchange

What can cause hyperphosphatemia?

- Chronic renal failure (decreased excretion, so builds up in body)

- Hypoparathyroidism (calcium low, so phosphorus high)

- Increased exogenous intake/increased intestinal absorption (e.g. high protein diet)

What can cause hypophosphatemia?

- Decreased exogenous intake/decreased intestinal absorption (severe malnutrition, absorption issue)

- Hyperparathyroidism (calcium high, so phosphorous low)

- Increased urinary excretion due to high sodium intake, metabolic or respiratory acidosis, or use of diuretics

What is the relationship between calcium and phosphorus?

inverse

What substrates are used in phosphorus testing?

*ammonium molybdate* complexes with phosphorous to form a colorless product measured by spectrophotometry. can also add *molybdenum blue* to measure a colored product

What are some interferences to phosphorus testing?

EDTA, reducing agents affect chromagen stability, hemolysis causes release of phosphorus, lipemia

What are the functions of Magnesium?

membrane stabilization, ion transport regulator, neuromuscular excitability, enzyme activation, contributor to bone mineralization and density

What causes hypermagnesemia?

decreased excretion, increased intake, dehydration, bone metastases

What are the S/S of hypermagnesemia?

decreased BP, bradycardia, skin flushing, increased temperature, nausea, vomiting, weakness, lethargy

What causes hypomagnesemia?

reduced intake, decreased absorption, increased excretion, meds, increased need (pregnancy, lactation)

What are the S/S of hypomagnesemia?

tremors, tetany, paralysis, coma

What substrates are used to measure magnesium?

calmagite or formazen dye forms the colored product

What is the most common method for measuring magnesium? What is the reference method/gold standard?

most common: spectrophotometry

reference method: atomic absorption

What can cause interference with magnesium testing?

anything that causes hemolysis (prolonged tourniquet use, delayed separation of sample) because Mg is found intracellularly in red cells, would cause a false increase

What specimen must be used for magnesium testing?

serum or heparinized plasma

What roles does bone play in our body? (4)

1. mechanical protection

2. direction of motion and facilitating the movement process

3. housing for blood-forming marrow

4. reservoir for mineral ions (Ca, Mg, P)

cells that promote bone resorption

osteoclasts

cells that promote bone formation, synthesize mineral matrix

osteoblasts

most abundant cell in the bone; encased and mature osteoblasts that maintain strength and health of bone

osteocytes

disease associated with defective bone and cartilage mineralization in children and bone mineralization in adults; *abnormal calcification* of bone takes place over surfaces where remodeling has taken place, leading to bone deformation and/or susceptibility to fractures

osteomalacia

What tests are performed to diagnose osteomalacia?

Pyridinoline (PD) and Deoxypyridinoline (DPD), which are both cross-links in skeletal tissue and act as collagen stabilizers

Osteocalcin

marker for bone formation, produced by osteoblasts; should be taken up by the bone in healthy patients, so if it is high in the blood, bone density is low

osteocalcin

progressive systemic skeletal disease, characterized by low bone mass, deterioration of bone tissue, with an increase in bone fragility and susceptibility to fracture

osteoporosis

Osteoporosis is the most prevalent metabolic done disorder in adults. In what areas are fractures most common?

spine, wrists/hands, hips

What are the primary and secondary causes of osteoporosis?

primary: age, menopause

secondary: meds (immunosuppressive, strong corticosteroids leach calcium)

What tests are performed to diagnose osteoporosis?

PTH levels (increased)

25-OH D3 (increased vitamin D)

Bone density scan

disorder caused by a lack of vitamin D, or calcium/phosphate; leads to softening and weakening of the bones, which can cause poor growth and skeletal abnormalities, especially with the legs (bowed)

rickets

What tests are performed to diagnose rickets?

ALP (increased)

serum calcium and phosphorus (decreased)

25-hydroxy D3 aka calcidiol (decreased)

1,25-dihydroxy vitamin D aka calcitriol (decreased)

PTH (increased, trying to increase calcium)

chronic, localized disease characterized by increased bone remodeling, bone hypertrophy, and abnormal bone structure; old bone does not get replaced

Paget's Disease

What are the most affected areas of Paget's disease? What can it progress to?

pelvis, skull, spine, legs

can progress to arthritis or bone tumors

What tests are performed to diagnose Paget's Disease?

ALP (increased)

Procollagen I (PINP) (increased)

group of cancers that include tumors that form in the bones and soft connective tissue

sarcoma

sarcoma most commonly found in adults over the age of 40, mostly affects hip area

Chondrosarcoma

sarcoma found in children and young adults, most affects hip and core area (sternum, ribs, pelvis)

Ewing's sarcoma

sarcoma found in children and young adults, begins in cells that form bone (arms, legs) so often diagnosed during puberty (long bone growth)

Osteosarcoma

What tests are performed to diagnose sarcomas?

any test which would reflect increased bone turnover:

Ca, P, vitamin D, ALP, LD (increased)

Osteocalcin (decreased, all taken up by bone)

What are some risk factors that may lead to reduced bone mass and increased risk of bone fracture?

Decreased bone mass from previous fractures

Advanced age

Family history of bone disease

Body weight less than 127 lbs

Physical inactivity

Inadequate nutrient intake

Long-term glucocorticoid therapy

Cigarette smoking

Excess alcohol ingestion

Medical conditions that cause hormone imbalance: Cushing's, hyperparathyroidism, vitamin D metabolism disorders, hyperthyroidism, certain malignancies

Explain the correlation between procalcitonin levels and sepsis. Is PCT found in healthy patients?

PCT levels increase as sepsis worsens (often a part of a sepsis panel)

PCT should not be found in healthy patients because healthy people because the gene is suppressed in healthy people

The majority of calcium is found in the skeleton, primarily as _______________

hydroxyapatite