Bio 201 Lecture 4 PDF

Bone Growth and Remodeling Ossification continues throughout life with the growth and remodeling of bones Bones grow in two directions – Length – Width 7-1  Bone Elongation Epiphyseal plate—a region of transition from c...

Bone Growth and Remodeling Ossification continues throughout life with the growth and remodeling of bones Bones grow in two directions – Length – Width 7-1  Bone Elongation Epiphyseal plate—a region of transition from cartilage to bone – Functions as growth zone where the bones elongate – Consists of typical hyaline cartilage in the middle – With a transition zone on each side where cartilage is being replaced by bone – Metaphysis is the zone of transition facing the marrow cavity 7-2  X-Ray of Child’s Hand Epiphyseal Plates Diaphysis Epiphysis Epiphyseal plate Metacarpal bone Epiphyseal plates 7-3 Courtesy of Utah Valley Regional Medical Center, Department of Radiology Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Zones of the Metaphysis Zone 1 Zone 5 1 Zone of reserve cartilage Typical histology of resting hyaline cartilage 2 Zone of cell proliferation Multiplying Chondrocytes multiplying and chondrocytes lining up in rows of small flattened lacunae Enlarging chondrocytes 3 Zone of cell hypertrophy Cessation of mitosis; enlargement of chondrocytes and thinning of lacuna walls Breakdown of lacunae 4 Zone of calcification Temporary calcification of cartilage matrix between Calcifying columns of lacunae cartilage 5 Zone of bone deposition Bone Breakdown of lacuna walls, marrow leaving open channels; death of chondrocytes; bone deposition by osteoblasts, Osteoblasts forming trabeculae of spongy bone Osteocytes Trabeculae of spongy bone Victor Eroschenko Figure 7.12 7-4 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Bone Widening and Thickening Interstitial growth—bones increase in length – Bone elongation is really a result of cartilage growth within the epiphyseal plate – Epiphyses close when cartilage is gone—epiphyseal line – Lengthwise growth is finished Occurs at different ages in different bones 7-5  Bone Widening and Thickening Appositional growth—bones increase in width throughout life – Deposition of new bone at the surface – Osteoblasts on deep side of periosteum deposit osteoid tissue Become trapped as tissue calcifies – Lay down matrix in layers parallel to surface Forms circumferential lamellae over surface – Osteoclasts of endosteum enlarge marrow cavity 7-6  Bone Remodeling Bone remodeling occurs throughout life—10% per year – Repairs microfractures, releases minerals into blood, reshapes bones in response to use and disuse – Wolff’s law of bone: architecture of bone determined by mechanical stresses placed on it and bones adapt to withstand those stresses Remodeling is a collaborative and precise action of osteoblasts and osteoclasts Bony processes grow larger in response to mechanical stress 7-7  Dwarfism Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Achondroplastic dwarfism – Long bones stop growing in childhood Normal torso, short limbs – Failure of cartilage growth in metaphysis – Spontaneous mutation produces mutant dominant allele Pituitary dwarfism – Lack of growth hormone – Normal proportions with short stature © The McGraw-Hill Companies, Inc./Joe DeGrandis, photographer 7-8 Figure 7.13  Physiology of Osseous Tissue Expected Learning Outcome – Describe the processes by which minerals are added to and removed from bone tissue. – Describe the role of the bones in regulating blood calcium and phosphate levels. – Name several hormones that regulate bone physiology and describe their effects. 7-9  Physiology of Osseous Tissue A mature bone remains a metabolically active organ – Involved in its own maintenance of growth and remodeling – exchange minerals with tissue fluid Disturbance of calcium homeostasis in skeleton disrupts function of other organ systems – Especially nervous and muscular 7-10  Mineral Deposition and Resorption Mineral deposition (mineralization)—crystallization process in which calcium phosphate and other ions are taken from the blood plasma and deposited in bone tissue – Osteoblasts produce collagen fibers that spiral the length of the osteon – Fibers become encrusted with minerals that harden the matrix Calcium and phosphate (hydroxyapatite) from blood plasma are deposited along the fibers 7-11  Mineral Deposition and Resorption Cont. Calcium and phosphate ion concentration must reach a critical value called the solubility product for crystal formation to occur Most tissues have inhibitors to prevent this so they do not become calcified Osteoblasts neutralize these inhibitors and allow salts to precipitate in the bone matrix First few crystals (seed crystals) attract more calcium and phosphate from solution 7-12  Mineral Deposition and Resorption Abnormal calcification (ectopic ossification) – May occur in lungs, brain, eyes, muscles, tendons, or arteries (arteriosclerosis) – Calculus: calcified mass in an otherwise soft organ such as the lung Mineral resorption—the process of dissolving bone and releasing minerals into the blood – Performed by osteoclasts at the ruffled border – Hydrogen pumps secrete hydrogen into space between the osteoclast and bone surface 7-13  Mineral Deposition and Resorption Cont. – Chloride ions follow by electrical attraction – Hydrochloric acid (pH 4) dissolves bone minerals – Acid phosphatase enzyme digests the collagen Orthodontic appliances (braces) reposition teeth – Tooth moves because osteoclasts dissolve bone ahead of the tooth, where the pressure on the bone is the greatest – Osteoblasts deposit bone more slowly in the low- pressure zone behind the tooth 7-14  Calcium Homeostasis Calcium and phosphate are used for much more than bone structure Phosphate is a component of DNA, RNA, ATP, phospholipids, and pH buffers Calcium needed in neuron communication, muscle contraction, blood clotting, and exocytosis Minerals are deposited in the skeleton and withdrawn when they are needed for other purposes 7-15  Calcium Homeostasis About 1,100 g calcium in adult body – 99% in the skeleton As easily exchangeable calcium ions and more stable hydroxyapatite reserve 18% of adult skeleton exchanged with blood each year Normal calcium concentration in blood plasma is 9.2 to 10.4 mg/dL—45% as Ca2+ can diffuse across capillary walls and affect other tissues; rest in reserve, bound to plasma proteins 7-16  Calcium Homeostasis Hypocalcemia is a blood calcium deficiency. Causes; – Excessive excitability of the nervous system leads to muscle spasm, or tetany (inability of the muscle to relax) – Reason for excessive excitibility: making Na channels more responsive: – Calcium binds the glycoproteins on the cell surface so (+) charge on the outside and (–) charge on the inside – When there is not enough Ca, voltage-gated Na channels open – Na easily get inside the cell and excites nerve and muscle cells. 7-17  Calcium Homeostasis Hypocalcemia cause; – Tetany (inability of the muscle to relax) begins when plasma calcium level falls to 6 mg/dL – One sign, induced by the blood pressure cuff: strong spasmodic flexion of wrist and thumb called: Trousseau – Chvostek’s sign: facial spasm (just 10% so it is not a determining point) 7-18  Calcium Homeostasis Hypocalcemia is a blood calcium deficiency. – At 4 mg/dL; muscles of the larynx contracts tightly, called: Laryngospasm, can cause suffocation. 7-19  Calcium Homeostasis Hypocalcemia caused by, – Vitamin D deficiency – Diarrhea – Thyroid tumors – Underactive parathyroids – Pregnancy and lactation – Accidental removal of parathyroid glands during thyroid surgery 7-20  Calcium Homeostasis Hypercalcemia is excessive blood calcium Causes; – Nerve and muscle cells are less excitable – At 12mg/dL and higher cause emotional disturbance, muscle weakness, slow reflexes and sometimes cardiac arrest. – How? Making Na channels less responsive – Too much Calcium can inhibit the Na channels (inhibit them opening) 7-21  Calcium Homeostasis Calcium homeostasis depends on a balance between dietary intake, urinary and fecal losses, and exchanges between osseous tissue Calcium homeostasis is regulated by three hormones: – Calcitriol, – calcitonin, and – parathyroid hormone 7-22  Calcitriol Synthesis and Action Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 7-dehydrocholesterol Ultraviolet light HO Vitamin D3 (cholecalciferol) CH2 HO Bone resorption Calcidiol Reduced excretion OH of Ca2+ CH2 Calcitriol HO OH Absorption of Ca2+ and CH2 phosphate HO OH Figure 7.14 7-23  Calcitriol Calcitriol—a form of vitamin D produced by the sequential action of the skin, liver, and kidneys Produced by the following process – Epidermal keratinocytes use UV radiation to convert a steroid, 7-dehydrocholesterol to previtamin D3 – Liver adds a hydroxyl group converting it to calcidiol – Kidneys add another hydroxyl group, converting that to calcitriol (most active form of vitamin D); also from fortified milk 7-24  Calcitriol Cont. Calcitriol behaves as a hormone that raises blood calcium concentration – Increases calcium absorption by small intestine – Increases calcium resorption from the skeleton – Promotes kidney reabsorption of calcium ions, so less lost in urine Necessary for bone deposition—need adequate calcium and phosphate Abnormal softness of bones in children (rickets) and in adults (osteomalacia) without adequate vitamin D 7-25  Calcium Homeostasis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Calcium Intake and Excretion Blood Bone Dietary requirement 1,000 mg/day Deposition by Absorption by osteoblasts Digestive tract digestive tract Calcitonin Calcitriol (weak effect) Ca2+ (9.2–10.4 mg/dL) Hydroxyapatite Ca10(PO4)6(OH)2 Kidneys Calcium carbonate Filtration CaCO3 Resorption by by kidneys osteoclasts Calcitriol PTH Reabsorption by kidneys Calcitriol (weak effect) PTH Fecal loss Urinary loss 350 mg/day 650 mg/day Figure 7.15 Calcitriol, calcitonin, and PTH maintain normal blood calcium concentration 7-26  Calcitonin Calcitonin—secreted by C cells (clear cells) of the thyroid gland when calcium concentration rises too high Lowers blood calcium concentration in two ways – Osteoclast inhibition Reduces osteoclast activity as much as 70% Less calcium liberated from bones – Osteoblast stimulation Increases the number and activity of osteoblasts Deposits calcium into the skeleton 7-27  Calcitonin Important in children, weak effect in adults – Osteoclasts more active in children due to faster remodeling and release 5 g or more calcium into blood each day. By inhibiting this activity calcitonin can significantly lower blood ca level in children – In adults, osteoclasts release only about 0.8 gram calcium per day. – Deficiency does not cause disease in adults – But may prevent bone loss in pregnancy and lactating women. 7-28  Parathyroid Hormone Parathyroid hormone (PTH)—secreted by the parathyroid glands which adhere to the posterior surface of thyroid gland PTH released with low calcium blood levels PTH raises blood calcium level by four mechanisms – Binds to receptors on osteoblasts Simulating them to secrete RANKL which raises the osteoclast population 7-29  Parathyroid Hormone Cont. – Promotes calcium reabsorption by the kidneys, less lost in urine – Promotes the final step of calcitriol synthesis in the kidneys, enhancing calcium-raising effect of calcitriol – Inhibits collagen synthesis by osteoblasts, inhibiting bone deposition secretion of low levels of PTH causes bone deposition, and can increase bone mass 7-30  Calcium Homeostasis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood Ca2+ Blood Ca2+ excess returns to normal Calcitonin secretion Reduced Less bone osteoclast resorption activity Increased More bone osteoblast deposition activity (a) Correction for hypercalcemia Figure 7.16a 7-31  Calcium Homeostasis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood Ca2+ Blood Ca2+ deficiency returns to normal Parathyroid hormone secretion Increased More bone osteoclast resorption activity Reduced Less bone osteoblast deposition activity More urinary Prevention of phosphate hydroxyapatite excretion formation Less urinary Conservation Figure 7.16b calcium of calcium excretion 7-32 (b) Correction for hypocalcemia  Phosphate Homeostasis Average adult has 500 to 800 g phosphorus 85% to 90% of phosphate is in the bones Normal plasma concentration is 3.5 to 4.0 mg/dL Occurs in two principal forms – HPO42− and H2PO4− (monohydrogen and dihydrogen phosphate ions) 7-33  Phosphate Homeostasis Phosphate levels are not regulated as tightly as calcium levels – No immediate functional disorders Calcitriol promotes its absorption by small intestine and promotes bone deposition PTH lowers blood phosphate level by promoting its urinary excretion 7-34  Other Factors Affecting Bone At least 20 or more hormones, vitamins, and growth factors affect osseous tissue Bone growth especially rapid in puberty and adolescence – Surges of growth hormone, estrogen, and testosterone occur and promote ossification – These hormones stimulate multiplication of osteogenic cells, matrix deposition by osteoblasts, and chondrocyte multiplication and hypertrophy in metaphyses 7-35  Other Factors Affecting Bone Cont. – Girls grow faster than boys and reach full height earlier Estrogen stronger effect than testosterone on bone growth – Males grow for a longer time and taller Anabolic steroids cause growth to stop – Epiphyseal plate “closes” prematurely – Results in abnormally short adult stature – Drinking more than 3, 12 ounce cola associated with bone loss in women. 7-36  Bone Disorders Expected Learning Outcomes – Name and describe several bone diseases. – Name and describe the types of fractures. – Explain how a fracture is repaired. – Discuss some clinical treatments for fractures and other skeletal disorders. 7-37  Bone Disorders Orthopedics—originated as the name implies, as the treatment of skeletal deformities in children Deals with the prevention and correction of injuries and disorders of bones, joints, and muscles Includes the design of artificial joints and limbs and the treatment of athletic injuries 7-38  Fractures and Their Repair Stress fracture—break caused by abnormal trauma to a bone – Falls, athletics, and military combat Pathological fracture—break in a bone weakened by some other disease – Bone cancer or osteoporosis – Usually caused by stress that would not break a healthy bone Fractures classified by structural characteristics – Direction of fracture line – Break in the skin – Multiple pieces 7-39  Types of Bone Fractures Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1. Simple (closed) fracture 2. Compound (open) fracture Nondisplaced: bone pieces remain in proper alignment Displaced: out of alignment Comminuted: a bone is (a) Nondisplaced (a) Nondisplaced (b) Displaced broken into 3 or more pieces Greenstick: one bone is incompletely broken on one side but merely bent on the opposite side (c) Comminuted (d) Greenstick 7-40 a: Custom Medical Stock Photo, Inc.; c: © Lester V. Bergman/Corbis; d: Custom Medical Stock Photo, Inc.Figure 7.17  Healing of Fractures An uncomplicated fracture heals in about 8 to 12 weeks Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Marrow cavity Fibrocartilage Hard callus Hematoma Soft callus Spongy bone New blood vessels Compact bone 1 Hematoma formation 2 Soft callus formation 3 Hard callus formation 4 Bone remodeling The hematoma is converted Deposition of collagen and Osteoblasts deposit a temporary Small bone fragments are to granulation tissue by invasion fibrocartilage converts granulation bony collar around the fracture to removed by osteoclasts, while of cells and blood capillaries. tissue to a soft callus. unite the broken pieces while osteoblasts deposit spongy ossification occurs. bone and then convert it to compact bone. Figure 7.18 7-41  The Treatment of Fractures Closed reduction—procedure in which the bone fragments are manipulated into their normal positions without surgery Open reduction—involves surgical exposure of the bone and the use of plates, screws, or pins to realign the fragments Cast—normally used to stabilize and immobilize healing bone 7-42  The Treatment of Fractures Traction—used to treat fractures of the femur in children – Aligns bone fragments by overriding force of the strong thigh muscles – Risks long-term confinement to bed – Rarely used for the elderly – Hip fractures are usually pinned in elderly and early ambulation (walking) is encouraged to promote blood circulation and healing Electrical stimulation accelerates repair – Suppresses effects of parathyroid hormone Orthopedics—branch of medicine that deals with prevention and correction of injuries and disorders of the bones, joints, and muscles 7-43 Open Reduction of an Ankle Fracture Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 7.19 7-44 © SIU/Visuals Unlimited; 7.22a: © Michael Klein/Peter Arnold, Inc.  Other Bone Disorders Osteoporosis—the most common bone disease – Severe loss of bone density Bones lose mass and become brittle due to loss of organic matrix and minerals – Affects spongy bone the most since it is the most metabolically active – Subject to pathological fractures of hip, wrist, and vertebral column – Kyphosis (widow’s hump)—deformity of spine due to vertebral bone loss – Complications of loss of mobility are pneumonia and thrombosis 7-45  Osteoporosis Estrogen maintains density in both sexes; inhibits resorption by osteoclasts – Testes and adrenals produce estrogen in men – In women, rapid bone loss after menopause since ovaries cease to secrete estrogen Osteoporosis is common in young female athletes. Why? with low body fat causing them to stop ovulating and ovarian estrogen secretion is low 7-46  Osteoporosis Cont. Treatments – Estrogen replacement therapy (ERT) slows bone resorption, but increases risk of breast cancer, stroke, and heart disease – Drugs Fosamax, Actonel destroy osteoclasts – PTH slows bone loss if given as daily injection – Best treatment is prevention: exercise and a good bone- building diet between ages 25 and 40 7-47  Other Bone Disorders Postmenopausal white women at greatest risk – Begin to lose bone mass as early as age 35 By age 70, average loss is 30% of bone mass – Risk factors: race, age, gender, smoking, diabetes mellitus, diets poor in calcium, protein, vitamins C and D 7-48  Spinal Osteoporosis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (a) (b) a: © Michael Klein/Peter Arnold, Inc.; b: © Dr. P. Marzzi/Photo Researchers, Inc. Figure 7.20 a,b 7-49