Lec 1 y 2 Bone Metabolism & Healing - olgun
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| What are the three bone cell types? | Osteoblasts, Osteoclasts, Osteocytes
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| What are Osteoblasts? | Bone cells that promote bone formation
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| What are Osteoclasts? | Bone cells that break down and reabsorb portions of the bone for release into systemic circulation
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| What are hydroxyapatite crystals? | It is the mineralized connective tissue in bone. It is formed by osteoblasts, that deposit a matrix of Type-I collagen and also release calcium, magnesium, and phosphate ions that combine chemically into the crystalline mineral hydroxyapatite
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| What is cortical bone? | cortical bone forms the cortex, or outer shell, of most bones. It is a dense bone whose anatomical functional unit is the osteon.
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| What is an osteon? | osteons consist of concentric layers, or lamellae, of compact bone tissue that surround a central canal, the Haversian canal. In the canal is the bone's nerve and blood supply. Osteoblasts form the lamellae from the most external inward toward the canal
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| What is trabecular bone? | Also called spongy bone, this is the type of tissue found in the medulla (center) of bones
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| What are the types of protein in bond? | proteogylcans, glycoproteins, & collagen (specifically Type I collagen)
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| What are the two ways our bones are developed? | Endochondral ossification and Intramembraneous Ossification
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| What is Intramembraneous Ossification? | Formation of bone tissue directly from connective tissue without a preliminary cartilage stage. Bones formed in this way include the skull and clavicles
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| What is Endochondral ossification? | The conversion of cartilage into bone. Most bones of the body are formed in this way
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| What are the four steps in intramembraneous ossification? | osteoblasts form a ossification center bone matrix is secreted within fibrous membrane Woven bone and periosteum form Bone collar of compact bone forms and red marrow appears
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| What is the periosteum? | a membrane that lines the outer surface of all bones
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| What is the red marrow? | the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells
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| What are the three types of cartilage? | Hyaline cartilage, Fiberous cartilage, Elastic cartilage
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| What is Hyaline cartilage? | hard material rich in Type 2 collagen & proteoglycan. It covers the end of bone to form the smooth articular surface of joints. found in the ear, larynx and between ribs and sternum. Bones use a hyaline cartilage intermediate in Endochondral ossification
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| What are the three sections of a long bone? | Epiphysis, Metaphysis, Diaphysis
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| What is the Epiphyseal Plate | epiphyseal plate is a hyaline cartilage plate in the metaphysis at each end of a long bone. The plate is found in children endochondral oss. is responsible for initial bone development via cartilage epiphyseal plates r responsible for longitudinal growth
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| What is a lamella? | Each of the concentric rings of an osteon, called lamella, is a layer of bone matrix in which the collagen fibers and mineral crystals align and run in a single direction
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| Why do fibers of adjacent lamella run in roughly opposite direction ? | Because it is optimal for withstanding torsion stresses, and inhibits crack propagation
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| What is a Lacuna? | a small space containing an osteocyte in bone or chondrocyte in cartilage
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| What are Haversian canals (1), which direction do they run (2)? | a series of tubes around narrow channels formed by lamellae. They are arranged in parallel to the long axis of the bone. The Haversian canals surround blood vessels and nerve cells in the bone and communicate with osteocytes in lacunae through canaliculi
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| What is the name of the canals that run perpendicular to Haversian canals? | Volkmann's canal
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| How are nutrients passed from one osteocyte to the next? | Within the canaliculi, the extensions of neighboring osteocytes touch each other and form gap junctions Gap junctions allow nutrients diffusing from the capillaries to cross these junctions
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| What do canaliculi connect | osteocytes
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| Do osteons exists within trabeculae? | No
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| What is the endosteum? | The endosteum (plural endostea) is a thin layer of connective tissue which lines the surface of the bony tissue that forms the medullary cavity of long bones where the trabecular bone is
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| What are the four defining characteristics of compact bone (Cortical Bone) | -External layer -Arranged in osteons -Lamellae are found around periphery and between osteons -Central canals connected to each other by perforating canals
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| What are the five defining characteristics of Trabecular Bone (spongy bone) | -No osteons -Arranged in trabeculae -Major type of tissue in short, flat, irregular bones -Much lighter than compact bone -Supports red bone marrow
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| What are the major roles of Parathyroid Hormone (PTH)in bone metabolism? | PTH helps to increase systemic Ca -converts Vitamin D to its active form -induces osteoblasts to secret M-CSF which helps to transform osteoclast precursors into osteoclasts -stimulate osteoblasts to release RANK & IL 6
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| What is the role of Vitamin D in bone metabolism | Vitamin D increases systemic Ca by: -increasing absorption of Ca in the GI -Increase Ca reabsorption in the kidney -Increases PTH affinity for osteoblasts while down regulating gene expression of PTH
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| What is the function of M-CSF | mononuclear phagocyte colony-stimulating factor (M-CSF) helps to mature stem cells into osteoclast precursors
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| What does Interleukin-6 do in bone metabolism? | Activates Osteoclasts to break down an absorb bone tissue
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| What does RANK ligand do in bone metabolism? | Activates Osteoclasts to break down an absorb bone tissue
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| Are Osteoblasts multinucleated? | No, but mature Osteoclasts are.
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| What is the role of Glucocorticoids in bone metabolism? | Glucocorticoids increase the production of RANK ligand by osteoblastic cells but decrease the production of osteoprotegerin(OPG). The net result is that more free RANK ligand is available to bind to RANK and thus promote bone loss
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| What is the role of osteoprotegerin (OPG) in bone metabolism? | OPG binds to RANK preventing it from inducing osteoclasts, and consequently reducing bone breakdown.
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| What disease forms when you have a mutation or loss of the RANK ligand gene? | osteopetrosis (excessive bone density) because of the loss of osteoclasts
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| What disease forms when you have a mutation or loss of the osteoprotegerin (OPG) gene? | osteoporosis (reduced bone density) because of a high nuber of overly active osteoclasts
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| What disease forms if you have a deficiency of carbonic anhydrase enzyme in your osteoclasts? | osteopetrosis
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| What does calcitonin do to osteoclasts? | It activates a cascade within the cell that inhibits bone reabsorption (downregulates the osteoclasts) - it works against the effects of the PTH hormone
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| CFU-GM is a pregenitor cell for what type of cell? | osteoclasts
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| CFU-F is a pregenitor cell for what type of cell? | osteoblasts
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| After osteoclasts have resorbed old bone, osteoblasts come in to fill the empty space left by the osteoclasts. What do they fill the cavity with initially that will eventually become mineralized and become bone? | osteoid
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| What two control groups regulate bone remodeling? | 1 - hormonal mechanisms maintain the calcium homeostasis in the blood; 2 - mechanical and gravitational forces acting on the skeleton
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| Woven bone in adults indicates what (two possibilities) | 1) Early in fracture repair or 2) bone forming tumors --- woven bone forms rapidly and is always pathogenic if found in the adult skeleton.
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| What are the four stages of bone healing? Which stage is the longest? | 1) Fracture hematoma, 2) Granulation tissue, 3) Bony callus formation, 4) Remodeling --- Steps 1-3 happen over 8-12 weeks, remodeling occurs over the next 6 months
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| What area is hematogenous osteomyelitis most likely to occur? | the metaphyseal area of the long bones because of the unique vascular supply in this region
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| What is type 1 osteoporosis? Does it effect males, females, or both? | Type 1 primary osteoporosis is due to an absolute increase in osteoclast activity. The increased number of osteoclasts that appears in the early postmenopausal skeleton is the direct result of estrogen withdrawal. Thus, it is only found in women.
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| What is type 2 osteoporosis? Does it effect males, females, or both? | Type 2 osteoporosis reflects decreased osteoblast activity. Happens in elderly people of both sexes.
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| What is osteomalacia? What deficiency is it associated with? | Osteomalacia is characterized by inadequate mineralization of bone matrix. It is associated with vitamin D deficiency, which reduces the rate of absorption of calcium across the lining of the intestines (this is called rickets in children)
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| A patient with bones that have an excessive amount of bone matrix and are brittle is most likely what disease? | osteopetrosis
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| What is scurvy? | Scurvy is characterized by the inability of osteoblasts to manufacture normal amounts of bone matrix (collagen). It is asscociated with hypovitaminosis C.
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| What is the range of normal blood calcium? What two hormones regulate intestinal absorption of calcium? | 8.5-10.5 mg/dL; Vitamin D and PTH
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| What hormone is the primary hormone that protects against hypocalcemia and acts on the bone, kidneys, and indirectly to the intestines? | PTH
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| When blood calcium is low PTH is secreted. Why is it that Vitamin D negatively inhibits PTH transcription when it also trying to increase blood calcium? | the negative vitamin D effect is a control mechanism so there isnt an overshoot of calcium increase.
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| What is the active form of vitamin D? | 1,25-dihydroxyvitamin D
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| What is vitamin D primarily bound to in the blood which transports the vitamin D and provides a reservoir of vitamin D that protects against Vitamin D deficiency? | vitamin D-binding protein (DBP)
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| Explain briefly how PTH effects the small intestine and bone. | Small intestine - no direct action; Bone - promotes osteoblastic growth and survival, regulates M-CSF, RANKL, and OPG production by osteoblasts
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| Explain briefly how PTH effects the kidneys and parathyroid gland. | Kidney - stimulates 1-alpha hydroxylase activity, stimulates calcium reabsorption and inhibits phosphorous reabsorption; Parathyroid Gland - No direct action
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| Explain briefly how active vitamin D effects the small intestine and bone. | Small intestine - increases calcium absorption by increasing TRPV channels, calbindin-D and PMCA expression - marginally increases Phosphorous absorption; Bone - sensitizes osteoblasts to PTH and regulates osteoid production and calcification
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| Explain briefly how active vitamin D effects the kidneys and parathyroid gland. | Kidney - minimal actions of calcium reabsorption, but promotes phosphorous reabsorption; Parathyroid gland - directly inhibits PTH gene expression and directly stimulates CaSR gene expression
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| What happens in primary hyperparathyroidism? | adenoma on parathyroid gland causes excessive production of PTH, resulting in hypercalcemia (but low serum Phosphorous) - kidney stones and phosphaturia are common, as well as decreased neurmuscular excitability and eventually osteoporosis
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