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Biochem 6200 > Calcium and hard tissue > Flashcards

Calcium and hard tissue Flashcards

1
Q

Calcium and hard tissue

A
  1. If it is in the Text and in the Notes it is Important. - probably review the slides for this one.
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2
Q

Bone is a

A

structural material

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3
Q

What is the Mineral Component of bone

A

Mineral Content Provides Stiffness and
Hardness to Bone and Teeth

Bone is Composed of: —  Collagen
—  Hydroxyapatite (Ca10[PO4]6[OH]2)
¢  Bone is a Composite ¢  50-60% of
Hydroxyapatite Plates
Fig 1-13 From Ten Cate’s Oral Histology, Sixth Edition
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4
Q

What is the Primary Protein Component of bone?

A

collagen

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5
Q

Enamel

A

¢ Matrix is Amelogenin ¢ Hydroxyapatite 90%

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6
Q

Dentin

A

¢ Matrix is Collagen (I) ¢ Hydroxyapatite 67%

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7
Q

WHY are bones a COMPOSITE STRUCTURE?

A

Composites can Combine Best of Two Materials
¢ Collagen is Tough but Not Strong
¢ Hydroxyapatite is Strong but Not Tough — Not Tough = Brittle, like glass
¢ Mineralized Tissue is Both Strong and Tough
¢ Structural Integrity of Bone is Dependent on the Interaction of Collagen and Hydroxyapatite

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8
Q

SOME DIFFERENCES BETWEEN BONE AND TEETH

A 
¢  Bone Has a Lower Mineral Content
¢  Bone is Maintained, Enamel is Not Maintained —  Bone Can Heal
—  Enamel Cannot Heal – Can Remineralize
—  Dentin Has a Limited Capacity to Heal
¢  Bone is Vascularized
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9
Q

PROCESS OF MINERALIZATION

A

Vesicles Containing a Saturated Solution of HA ¢ Initiates Crystallization and Rupture Vesicle
¢ Osteoblasts Excrete Matrix Proteins
¢ Pyrophosphate can Block Mineralization
¢ Alkaline Phosphatase Degrades Pyrophosphate

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10
Q

REMODELING CYCLE

A

¢ Bone is Dynamic Structure
¢ Constantly Building and Resorbing Bone
¢ Many Factors Will Influence Balance — Serum Calcium
— Hormones
— Cytokines

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11
Q

CELLS INVOLVED IN REMODELING

A

§ Osteoblasts Build Bone
§ Osteoclasts Resorb Bone
§ Osteoblasts and Osteoclasts are from Different Lineages

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12
Q

How do the Remodeling Cycle and Serum Calcium Levels Affect one Another?

A

Decrease in bone mass = increase in serum Ca, and vice versa. Increase in serum Ca leads to bone synthesis, and the other end leads to bone resorption.

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13
Q

Promote Resorption

A

IL-1, IL-6 and TNF

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14
Q

Inhibit Resorption

A

Calcium
¢ Estrogens
¢ Calcitonin
¢ Tumor Growth Factor-β ¢ IL-17

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15
Q

Osteoblasts and Osteoclasts are from

A

Different Lineages

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16
Q

OSTEOCLAST ACTIVATION

A

Rank connects to RankL to break down, Osteoprogenerin to inhibit.

RankL leads to formation of:
Lysosomal Enzymes Collagenases Cathepsins
Acidic pH

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17
Q

BYPRODUCTS of osteoclasts

A 
Calcium
¢  Collagen Peptides or Fragments
¢  Pyridinoline Crosslink
Fragments ¢  Telopeptides NTX and
CTX

Can Detect Byproducts in Serum and Urine
¢ Hydroxyproline

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18
Q

Osteoblast activation

A

cAMP Vitamin D TGF-β IGF-1 PDGF — RankL is attached for activation.

When activated forms: Collagen I, Alkaline Phosphatase, Osteocalcin, Fibronectin Bone Sialoprotein, Osteopontin

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19
Q

RankL

A

Osteoblast surface protein. Activates osteoclasts.

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20
Q

CALCIUM METABOLISM

A

Bone is a Calcium Store

¢ Hormonal Control of Calcium Homeostasis ¢ Vitamin D Plays an Important Role

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21
Q

DISTRIBUTION OF CALCIUM

A

99% of Calcium is contained in Mineralized
Tissue
¢ Remaining 1% is circulated in a Bound or Ionic Form

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22
Q

SERUM CALCIUM

A

¢ Ionized Calcium 50%
¢ Protein Bound Calcium 40% — Bound to Albumin
¢ Citrate or Phosphate Bound Calcium 10%

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23
Q

MEASURING SERUM CALCIUM LEVELS

A

Most Tests Measure Total Calcium
¢ Ionic Calcium is Physiologically Active
¢ Ionic Levels not Affected by Albumin Bound Calcium
¢ Decrease in Albumin can be From Liver Disease, Malnutrition.
¢ Need a Correction Factor to Determine Total Calcium Levels

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24
Q

HORMONAL CONTROL OF CALCIUM

A

¢ Parathyroid Hormone is the Primary Regulator
of Calcium Levels
¢ 84 Amino acid Protein Synthesized by the Parathyroid Gland
¢ Triggers an Increase in Serum Calcium
¢ Production is Stimulated by Low Plasma Calcium

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25
Q

CALCIUM SENSING RECEPTORS

A

¢ Found on Several Cell Types
¢ Parathyroid Gland: Parathyroid Hormone
¢ Thyroid C-Cells: Calcitonin
¢ Kidney Tubules: Regulates Calcium Excretion

26
Q

OTHER HORMONES THAT REGULATE CALCIUM

A

Calcitonin inhibits Bone Resorption
¢ 32 Amino acid Protein Produced by C-Cells
¢ Other Hormones: — Thyroid Hormone
— Estrogen and Testosterone
— Insulin Like Growth Factors (IGF-1 and IGF-2)

27
Q

ABSORBED AND EXCRETED CALCIUM

A

Calcium is Absorbed in the Small Intestine — Active Transport Regulated by Vitamin D
— Transport Based on Relative Serum/Gut Levels
¢ Calcium is Excreted in Urine and Feces
— Kidneys are Regulated by PTH
— Large Intestine Levels Governed by Small Intestine

28
Q

VITAMIN D

A

Vitamin D plays and Important Role in Calcium
Regulation
¢ Increases Serum Calcium
¢ Vitamin D increases Gut Adsorption of Calcium
¢ Vitamin D increase Bone Adsorption

29
Q

VITAMIN D SYNTHESIS

A

Precursor Synthesized in Skin
¢ Stored in Liver
¢ Converted to Active Form in the Kidney ¢ 1α hydroxylase is Point of Regulation

30
Q

1α-HYDROXYLASE STIMULATION

A

Parathyroid Hormone ¢ Low Calcium
¢ Low Vitamin D
¢ Calcitonin

31
Q

1α-HYDROXYLASE INHIBITION

A

Low Parathyroid Hormone
¢ High Serum Calcium
¢ High Vitamin D
¢ 24-Hydroxylase can Inactivate Liver Precursor 25-hydroxycholecalciferol

32
Q

Calcium is Important for:

A

Clotting, Muscle Contraction, Cardiovascular Function

33
Q

Serum Calcium Levels Trigger

A

Production of

Regulatory Hormones

34
Q

DISORDERS OF CALCIUM AND BONE

A

Hypercalcemia
¢ Hypocalcemia
¢ Metabolic Disorders of The Bone

35
Q

HYPERCALCEMIA – EXCESS CALCIUM

A 
Common Causes
¢  Primary Hyperparathyroidism
¢  Malignant Disease
¢  Iatrogenic Vitamin D
Uncommon Causes
¢  Thyrotoxicosis
¢  Multiple Myeloma ¢  Sarcoidosis
¢  Renal Failure
¢  Drug Induced —  Lithium
—  Thiazide Diuretics
¢  Familial Hypocalciuric Hypercalcemia
36
Q

HYPERPARATHYROIDISM (HPT)

A

Increase in Production of Parathyroid Hormone
¢ Diagnosed By ‘bone, stones and abdominal groans
¢ 80-85% are caused by an Adenoma
¢ Occurs in 1-500 to 1-1000 in Population
¢ Intact Parathyroid Hormone is an indication of HPT

37
Q

EFFECT ON BONE - HPT

A

HPT increases Bone remodeling
¢ Results in Osteopenia
¢ Six Months After Surgery Most but not all Bone Density back to Normal

38
Q

HYPERCALCEMIA ASSOCIATED WITH MALIGNANCY (HCM)

A

Primary Cause of Hypercalcemia from Parathyroid Hormone-Related Protein (PTHrP)
¢ PTHrP has Sequence Homology with PTH
— Hypophosphatemia, Phosphaturia, Increased Renal
Calcium Resorption, Osteoclast Activation
¢ PTHrP Produced by Tumors
¢ Common Tumors: Breast, Lung, Kidney other Solid Tumors
¢ Less Common Tumors: Hematologic, Gastrointestinal, Head and Neck

39
Q

HCM FROM BONE TUMOR OR METASASES

A

¢ Locally Active
¢ Alters RANKL/Osteoprogenerin (OPG) Balance
¢ Produces Cytokines and Growth Factors

40
Q

SYMPTOMS AND TREATMENT 0 HCM

A 
Dehydration
¢  Vomiting
¢  Reduced Renal Perfusion
¢  Treatment with Bisphosphonates
¢  Bisphosphonates Inhibit Osteoclast Activity
41
Q

SIDE EFFECTS OF BISPHOSPHONATES

A

Drug against hypercalcemia:

Inhibit Remodeling ¢  Osteonecrosis in
¢  Slow Fracture Healing
¢  Brittle Bones
¢  Long Half-Time are Incorporated in Bone
Mandible
¢  Typified by Oral Lesions
42
Q

VITAMIN D - Hypercalcemia

A

Vitamin D is the Third Leading Cause of
Hypercalcemia
¢ Normally Obvious Cause
¢ Also Measure Levels Vitamin D3, Vitamin D2 and 1,25(OH)2D3

43
Q

HYPOCALCEMIA

A

Drop in Serum Albumin (Adjusted Calcium
Levels)
¢ Changes in Ionized Calcium from pH Change

44
Q

SYMPTOMS OF HYPOCALCEMIA

A

Neuromuscular Irritability ¢ Chveostek’s Sign
¢ Trousseau’s Sign
¢ Numbness
¢ Tingling ¢ Cramps ¢ Tetany ¢ Seizures

45
Q

HYPOPARATHYROIDISM - cause

A

Usually a Result of a Damaged Parathroid Gland — Surgery
— Tumor
— Thyroid Disease
— Parathroid Disease

46
Q

PTH RESISTANCE

A 
¢  Increase in PTH ¢  Hypomagnesemia
¢  End Organ Resistance ¢  Need Magnesium for to PTH PTH to Bind to
¢  Usually Genetic Defect
—  G-protein
Secretory Granules
47
Q

ABNORMAL METABOLISM OF VITAMIN D

A

Vitamin D Deficiency
— Reduced Exposure to Sunlight — Poor Dietary Intake
— Malabsorption
¢ Tissue Resistance to Vitamin D
¢ Also a Result of Clinical Conditions — Liver Disease
— Renal Failure

48
Q

METABOLIC BONE DISEASE

A

Osteoporosis

¢ Paget’s Disease ¢ Osteomalacia

49
Q

OSTEOMALACIA

A

Defects in Hydroxyapatite Formation ¢ Due to Vitamin D Deficiency
¢ Rickets

50
Q

RICKETS

A 
Noted During the Industrial
Revolution
¢  Lack of Sunlight Because of Pollution and Narrow Alley’s
¢  Inhibited Vitamin D Metabolism
¢  Bone and Muscle Weakness
¢  Skeletal Deformity – Large
Head, Spinal Curvature
¢  Cod Liver Oil
51
Q

Rickets diagnoses

A

Rickets can be Difficult to Diagnose from
Skeletons
— Bone Remodels
— Only Sever Cases are Obvious
¢ Dentin Would have ‘Gaps’ Due to Rickets
— Interglobular Dentin
— Observed in Animals and Some Human Cases of Vitamin D Deficiency
— Dentin Does Not Remodel
¢ Examine Skeletal Remains vs. Healthy Adults

52
Q

OSTEOPOROSIS

A

Loss of Mineral Density with Age – Peak Density
at 30
¢ Increase Risk of Fracture
¢ Relative Rates of Bone Synthesis and Resorption Change

53
Q

TREATMENTS FOR OSTEOPOROSIS

A

Estrogen (Hormone Replacement Therapy) ¢ Bisphosphonates
¢ Calcitonin
¢ PTH(1-34 Amino Acid Sequence)

54
Q

PAGET’S DISEASE

A 
Large Numerous multinucleate Osteoclasts
¢  Large Number of Osteoblasts
¢  Increase in Alkaline Phosphatase
¢  Large Misshapen Bones
¢  Less Dense, Brittle
¢  High Serum Content of Hydroxyproline, Pyridinolines and Telopeptides
55
Q

Paget’s Disease cause/treatment

A 
Cause is Unknown —  Genetic?
—  Early Childhood Viral Infection?
¢  Most Common in Europe, Australia and New
Zeeland
¢  Some are Asymptomatic
¢  Treatments:
—  Bisphosphonates —  Calcitonin
56
Q

SPACE TRAVEL

A

Microgravity is known to have a profound effect
on Bone Density and Calcium Metabolism
¢ 1% Bone Mass is Lost Per Month of Space Travel
¢ Roughly the same as bed rest or 1 Year of Osteoporosis
¢ Mission to Mars Could Result in 50% Bone Mass Loss

57
Q

Unloading of Bone Result in a

A

Decrease of Bone Synthesis while Maintaining Same Level of Bone Degradation.
¢ Serum Calcium Levels Increase.
¢ Decrease in PTH

58
Q

CONSEQUENCES of being in space

A

Gut absorption of Calcium is Decreased
¢ Increase in Serum Calcium does not Result in New Bone Formation
¢ Body is Metabolizing Bone as its Primary Calcium Source Rather than the Diet

59
Q

EXTENSIVE EXERCISE AND BONE LOSS

A

For Competitive Cyclists Bone Density Decrease
was observed after nine months of training
¢ Even after a three month rest period the Bone Density did not Return.

60
Q

POTENTIAL REASONS for bone loss from exercise

A

(1) an increase in PTH, possibly consequent to a decrease in serum calcium during exercise as a result of excess dermal calcium loss
¢ (2) insufficient energy availability during periods of heavy training and competing
¢ (3) suppression of sex hormones
¢ (4) an increase in stress hormones and pro-
inflammatory cytokines
¢ (5) self-imposed restriction on weight bearing activities in favor of cycling.

Biochem 6200 (18 decks)

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