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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
CALCIUM SENSING RECEPTORS
¢ Found on Several Cell Types ¢ Parathyroid Gland: Parathyroid Hormone ¢ Thyroid C-Cells: Calcitonin ¢ Kidney Tubules: Regulates Calcium Excretion
26
OTHER HORMONES THAT REGULATE CALCIUM
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
ABSORBED AND EXCRETED CALCIUM
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
VITAMIN D
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
VITAMIN D SYNTHESIS
Precursor Synthesized in Skin ¢ Stored in Liver ¢ Converted to Active Form in the Kidney ¢ 1α hydroxylase is Point of Regulation
30
1α-HYDROXYLASE STIMULATION
Parathyroid Hormone ¢ Low Calcium ¢ Low Vitamin D ¢ Calcitonin
31
1α-HYDROXYLASE INHIBITION
Low Parathyroid Hormone ¢ High Serum Calcium ¢ High Vitamin D ¢ 24-Hydroxylase can Inactivate Liver Precursor 25-hydroxycholecalciferol
32
Calcium is Important for:
Clotting, Muscle Contraction, Cardiovascular Function
33
Serum Calcium Levels Trigger
Production of | Regulatory Hormones
34
DISORDERS OF CALCIUM AND BONE
Hypercalcemia ¢ Hypocalcemia ¢ Metabolic Disorders of The Bone
35
HYPERCALCEMIA – EXCESS CALCIUM
``` 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
HYPERPARATHYROIDISM (HPT)
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
EFFECT ON BONE - HPT
HPT increases Bone remodeling ¢ Results in Osteopenia ¢ Six Months After Surgery Most but not all Bone Density back to Normal
38
HYPERCALCEMIA ASSOCIATED WITH MALIGNANCY (HCM)
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
HCM FROM BONE TUMOR OR METASASES
¢ Locally Active ¢ Alters RANKL/Osteoprogenerin (OPG) Balance ¢ Produces Cytokines and Growth Factors
40
SYMPTOMS AND TREATMENT 0 HCM
``` Dehydration ¢ Vomiting ¢ Reduced Renal Perfusion ¢ Treatment with Bisphosphonates ¢ Bisphosphonates Inhibit Osteoclast Activity ```
41
SIDE EFFECTS OF BISPHOSPHONATES
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
VITAMIN D - Hypercalcemia
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
HYPOCALCEMIA
Drop in Serum Albumin (Adjusted Calcium Levels) ¢ Changes in Ionized Calcium from pH Change
44
SYMPTOMS OF HYPOCALCEMIA
Neuromuscular Irritability ¢ Chveostek’s Sign ¢ Trousseau’s Sign ¢ Numbness ¢ Tingling ¢ Cramps ¢ Tetany ¢ Seizures
45
HYPOPARATHYROIDISM - cause
Usually a Result of a Damaged Parathroid Gland — Surgery — Tumor — Thyroid Disease — Parathroid Disease
46
PTH RESISTANCE
``` ¢ Increase in PTH ¢ Hypomagnesemia ¢ End Organ Resistance ¢ Need Magnesium for to PTH PTH to Bind to ¢ Usually Genetic Defect — G-protein Secretory Granules ```
47
ABNORMAL METABOLISM OF VITAMIN D
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
METABOLIC BONE DISEASE
Osteoporosis | ¢ Paget’s Disease ¢ Osteomalacia
49
OSTEOMALACIA
Defects in Hydroxyapatite Formation ¢ Due to Vitamin D Deficiency ¢ Rickets
50
RICKETS
``` 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
Rickets diagnoses
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
OSTEOPOROSIS
Loss of Mineral Density with Age – Peak Density at 30 ¢ Increase Risk of Fracture ¢ Relative Rates of Bone Synthesis and Resorption Change
53
TREATMENTS FOR OSTEOPOROSIS
Estrogen (Hormone Replacement Therapy) ¢ Bisphosphonates ¢ Calcitonin ¢ PTH(1-34 Amino Acid Sequence)
54
PAGET’S DISEASE
``` 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
Paget's Disease cause/treatment
``` Cause is Unknown — Genetic? — Early Childhood Viral Infection? ¢ Most Common in Europe, Australia and New Zeeland ¢ Some are Asymptomatic ¢ Treatments: — Bisphosphonates — Calcitonin ```
56
SPACE TRAVEL
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
Unloading of Bone Result in a
Decrease of Bone Synthesis while Maintaining Same Level of Bone Degradation. ¢ Serum Calcium Levels Increase. ¢ Decrease in PTH
58
CONSEQUENCES of being in space
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
EXTENSIVE EXERCISE AND BONE LOSS
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
POTENTIAL REASONS for bone loss from exercise
(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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