Patofysiologi. Benvävnad/Leder

Transcription

1 Patofysiologi Benvävnad/Leder

2 Factors That Affect Bone Growth 1. Minerals 2. Vitamins 3. Hormones 4. Exercise

3 Factors That Affect Bone Growth Calcium Phosphorus Magnesium Boron Manganese Minerals Makes bone matrix hard Hypocalcemia: low blood calcium levels. Hypercalcemia: high blood calcium levels. Makes bone matrix hard Deficiency inhibits osteoblasts May inhibit calcium loss, increase levels of estrogens Inhibits formation of new bone tissue

4 Factors That Affect Bone Growth Vitamins Vitamin A Controls activity, distribution, and coordination of osteoblasts/osteoclasts Vitamin B12May inhibit osteoblast activity Vitamin C Helps maintain bone matrix, deficiency leads to decreased collagen production which inhibits bone growth and repair Vitamin D (scury) disorder due to a lack of Vitamin C (Calcitriol) Helps build bone by increasing calcium absorption. Deficiencies result in Rickets in children

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6 Factors That Affect Bone Growth Hormones Human Growth Hormone Promotes general growth of all body tissue and normal growth in children Insulin-like Growth Factor Stimulates uptake of amino acids and protein synthesis Insulin Thyroid Hormones Estrogen and Testosterone Promotes normal bone growth and maturity Promotes normal bone growth and maturity Increases osteogenesisat puberty and is responsible for gender differences of skeletons

7 Bone Fractures Terms: Closed/Open Partial/Complete Displaced/Nondisplaced Simple/Compound Other Fractures: Spiral Transverse Longitudinal Pathologic

8 Bone fractures are very painful!

9 Types of Fractures Simple - bone breaks cleanly and does not penetrate the skin. Compound (open) - broken ends of bone protrude through soft tissues and the skin. Comminuted - bone breaks into many fragments. Compression - bone is crushed. Depressed - broken portion is pressed inward. Impacted - broken ends are forced into each other. Spiral - ragged break caused by excessive twisting force. Greenstick - Bone breaks incompletely.

10 Vertebral fractures Advanced Osteoporosis and 'Dowager's Hump' Loss of height Spine deformity Often severe pain, Loss of mobility

11 Subluxation: an incomplete or partialdislocationof a joint or organ. Luxation: a complete dislocation of A joint or organ.

12 Bone Fracture Repair

13 Steps in Fracture Repair 1. Formation of a fracture hematoma Immediately after the fracture, there is a sharp fracture line with associated soft tissue swelling. At the fracture Site, there is abundant hematoma with beginning fibroblastic penetration.

14 Steps in Fracture Repair 2. Fibrocartilaginous Callus Formation At 2 weeks there is much visible callus. There is also bone resorptionand osteoporosis, There has been migration of chondroblasts into the area and cartilage is beginning to cover the ends of the fracture. New osteoustissue is produced enchondrally.

15 Bone Fracture Repair

16 Steps in Fracture Repair 3. Bony Callus Formation At 2 months, bony callus with sharp margins bridges the fracture and the fracture line itself begins to disappear.

17 Steps in Fracture Repair 4. Bone Remodeling At 5-6 months, the marrow cavity is continuous and the compact bone of the diaphysis has been reformed.

18 Bone Disorders Osteopenia: refersto bonemineral density(bmd) that is lowerthannormal peakbmd butnot lowenoughto be classified as osteoporosis Osteoporosis:Loss of both bone salts and collagen fibers. Increased osteoclast activity and decreased osteoblast activity Risk Factors: European/Asian ancestry Family history Small body build Inactive lifestyle Cigarette smoking More than two drinks per day

19 Defining Osteoporosis systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk True Definition: bone with lower density and higher fracture risk WHO: utilizes Bone Mineral Density as definition (T score <-2.5); surrogate marker

20 Osteoporosis Mechanisms causing osteoporosis Imbalance between rate of resorptionand formation Types of osteoporosis Type I Type II Secondary

21 Osteoporosis -types Postmenopausal osteoporosis (type I) Caused by lack of estrogen Causes PTH to overstimulate osteoclasts Excessive loss of trabecular bone Age-associated osteoporosis (type II) Bone loss due to increased bone turnover Malabsorption Mineral and vitamin deficiency

22 Menopausal Osteoporosis Reduced bone mineral mass Normal mineral to matrix ratio. Estrogen deficiency The resorption cavities go a little deeper and resorption lasts a little longer, and the bone formation increases but doesn't quite match the higher resorption rate.

23 Secondary osteoporosis

24 Steroid Induced osteoporosis Corticosteroids increase the bone resorption rate and depth, similar to menopause. The steroids block action of osteoblasts, so the bone formation does not increase.

25 Osteoporosis Most common bone disease Bones lose mass & become brittle due to loss of both organic matrix & minerals risk of fracture of hip, wrist & vertebral column lead to fatal complications such as pneumonia widow s (dowager s) hump is deformed spine Postmenopausal white women at greatest risk by age 70, average loss is 30% of bone mass ERT (EstrogenReplacementTerapy)slows its progress, but best treatment is prevention -- exercise & calcium intake (1000 mg/day) between ages 25 and 40 25

26 Osteoporosis 2 Estrogen maintains density in both sexes (inhibits resorption) testes and adrenals produce estrogen in men rapid loss after menopause Treatment ERT slows bone resorption, but increases risk breast cancer, stroke and heart disease PTH (ParaThyreoideaHormon) slows bone loss if given daily injection Forteoincreases density by 10% in 1 year may promote bone cancer best treatment is prevention --exercise and calcium intake (1000 mg/day) between ages 25 and 40 26

27 Spinal Osteoporosis 27

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29 Bone Disorders Osteomalacia: Loss of bone salts but not collagen due to poor diet, decreased absorption of calcium, and vitamin D deficiency. Calcium is not deposited in the bones. Bones become brittle. Basically a demineralization of bone Example: Ricketsin young children Bones become soft. Bowing of the bones, and other deformities occur.

30 Osteomalacia Reduced mineralization of bone matrix due to calcium deficiency. Calcium deficiency Osteomalacia results when the osteoid does not have mineral.

31 Introduction Osteomalacia is known as the softening of bones due to insufficient vitamin D, or problems with the break down of this vitamin. This disease is also known as rickets in children.bones with osteomalacia have sufficient amounts of collagen which gives the bones their structure, but they lack calcium. The softness of the bones is more likely to cause bow and fractures.

32 Causes/Rick Factors The most common cause of osteomalacia is a deficiency of vitamin D. Vitamin D insufficiency can cause osteomalacia because vitamin D facilitates calcium absorption and other minerals in the gastrointestinal tract necessary for bone building. Lack of vitamin D, calcium and other minerals aren t absorbed efficiently, so they are not available for mineralization in the bone building process. This then result in soft bones. Insufficient sunlight exposure Sunlight makes vitamin D in your skin. Therefore osteomalacia can develop in people who spend little time in the sunlight, Insufficient vitamin D intake A diet low in vitamin D is the most common cause seen worldwide. Certain Surgeries The removal of part or all of your stomach known as gastrectomy, can lead to this disease because the stomach breaks down foods to release vitamin D and other materials, bypassing your small intestine can lead to osteomalacia. Chronic pancreatitis Pancreatitis is the long-standing inflammation of your pancreas, an organ that makes digestive enzymes and hormones Chronic sprue In this autoimmune disorder, Damaged intestinal lining doesn t absorb nutrients, such as vitamin D, as well as a healthy one would.

33 Bone Disorders Paget s Disease: Abnormal bone remodeling resulting in irregular thickening and thinning of bone through remodeling Osteomyelitis: Infection of bone most commonly by Staphylococcus aureus Osteogenicsarcoma: Bone cancer that affects osteoblasts at the metaphyses of long bones. Most common in teenagers

34 Bone pathologies Primary bone cancer: the cancer started in the bone. Metastatic or secondary bone cancer: did not start in the bone but has spread to the bone from other organs. E.g. when lung cancer spreads to the bones.

35 Primary bone cancer Osteosarcoma: cancerous tumour of the bone itself, and it is the most common primary bone cancer. Chondrosarcoma: cancer of cartilage cells and the second most common primary bone cancer. After age 20, the risk of developing chondrosarcoma continues to rise until reaching about 75 years.

36 Secondary bone cancers Lymphoma: Non-Hodgkin lymphomas generally develop in lymph nodes but sometimes start in the bone. Primary non-hodgkin lymphoma, multiple sites in the body are usually involved. Multiple myeloma: Although multiple myeloma almost always starts in bones, do not consider this a bone cancer because it develops from the plasma cells of the bone marrow

37 Arthritis: Bone Disorders Osteoarthritis: DJD degenerative joint disease Inflammatory Joint Disease: Rheumatoid arthritis: Initially may be caused by transient infection that results in autoimmune attacks against collagen in the bones at joints. Gouty Arthritis: Build-up of uric acid in the joints due to metabolic problems with handling the amino acid cystine.

38 Bone Disorders Infectious arthritis: Lymes disease

39 Infection

40 Rheumatoid arthritis (RA) Systemic disease of joints. Inflammatory condition. Idiopathic disease that involves immune-mediated mediated destruction of joints. Acute inflammation: excessive production of synovial fluid, increased blood flow, neutrophil, pain, swelling and joint stiffness.

41 RA, Etiology Probable background genetic susceptibility (multiple genes/risk factors involved) Concordance rates 15-30% identical twins times more prevalent in Women>Men Likely environmental triggers in people with genetic susceptibility Not seen until late 18th century in Europe

42 Genetic Risk Factors Family history Female Sex Specific genes: HLA-DR4

43 What is the cause of this disease? The exact cause of RA is unknown. Suspected causes are: Bacterial Infection Genetic Marker Stress Viral Infection Environmental Triggers Tobacco, Caffeine

44 How does the immune system play a role in this disease In RA, for some unknown reason, the immune system considers its own joint tissues foreign. White blood cells that normally protect the body, migrate to the joint cavity. Synoviumbecomes inflammedand fluid, causing synovitis. Lymphocytes, Macrophages, continue to enter the joint cavity and multiply, differentiate, and release inflammatory mediators, cytokines, leukotrienes, and prostaglandins.

45 Within weeks the synovium becomes thickened. The mass of synovial tissue that spreads over the top of cartlidge in a rheumatoid joint is called a pannus, made of white blood cells: macrophages, B&T Cells, neutrophils, plasma cells, NK cells, and T Helper cells.

46 These cells produce the Rheumatoid Factor, prostaglandins, cytokines and other mediators. Over time, the chemicals from the cells Over time, the chemicals from the cells damage cartilage, ligaments, tendons, and bone.

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48 Comparison of normal joint and rheumatoid arthritic joint

49 Symmetric polyarthritis RA, Clinical Features How to Differentiate from other Osteoarthritis Usually small-medium joints are involved Generally chronic disease (20% acute onset) Often leads to erosive, deforming, and disabling disease 20% have extra- articular manifestations

50 Gout

51 Definition Gout is a heterogeneous disorder that results in the deposition of uric acid salts and crystals in and around joints and soft tissues or crystallization of uric acid in the urinary tract. Uric acid is the normal end product of the degradation of purinecompounds. Major route of disposal is renal excretion Humans lack the enzyme uricaseto break down uric acid into more soluble form. Metabolic Disorder underlying gout is hyperuricemia. Defined as 2 SD above mean usually 7.0 mg/dl. This concentration is about the limit of solubility for (monosodium urate) MSU in plasma. At higher levels, the MSU is more likely to precipitate in tissues.

52 Epidemiology Most common of microcrystalline arthropathy. Incidence has increased significantly over the past few decades. Affects about 2.1million worldwide Peak incidence occurs in the fifth decade, but can occur at any age Gout is 5X more common in males than pre-menopausal females; incidence in women increases after menopause. After age 60, the incidence in women approaches the rate in men.

53 Classification of Hyperuricemia Uric acid overproduction Accounts for 10% of hyperuricemia Defined as 800mg of uric acid excreted Acquired disorders Excessive cell turnover rates such as Paget s disease, hemolytic anemias Genetic disorders: derangements in mechanisms that regulate purine neucleotide synthesis. Uric acid underexcretion Accounts for >90% of hyperuricemia Diminished tubular secretory rate, increased tubular reabsorption, diminished uric acid filtration Drugs, other systemic disease that predispose people to renal insufficiency

54 Predisposing Factors Heredity Drug usage Renal failure Hematologic Disease Trauma Alcohol use Psoriasis Poisoning Obesity Hypertension Organ transplantation Surgery

55 Pathogenesis of Gouty Inflammation Urate crystals stimulate the release of numerous inflammatory mediators in synovial cells and phagocytes The influx of neutrophils is an important event for developing acute crystal induced synovitis Chronic gouty inflammation associated with cytokine driven synovial proliferation, cartilage loss and bone erosion

56 Presenting Symptoms Systemic: fever rare but patients may have fever, chills and malaise Musculoskeletal: Acute onset of monoarticular joint pain. First MTP most common. Usually affected in 90% of patients with gout. Other joints knees, foot and ankles. Less common in upper extremities Postulated that decreased solubility of MSU at lower temperatures of peripheral structures such as toe and ear Skin: warmth, erythema and tenseness of skin overlying joint. May have pruritus GU: Renal colic with renal calculi formation in patients with hyperuricemia

57 Definitive diagnosis only possible by aspirating and inspecting synovial fluid and demonstrating crystals Polarized microscopy, the crystals appear as bright crystals that are yellow Diagnosis

58 Synovial Fluid Findings Needle shaped crystals of monosodium urate monohydrate that have been engulfed by neutrophils

59 Gout Gout is defined as a peripheral arthritis resulting from the deposition of sodium urate crystals in one or more joints.

60 Pathophysiology Primary gout: Overproducers: 10% Under-excretors: 90% Secondary gout: Excess nucleoprotein turnover (lymphoma, leukemia) Increased cell proliferation/death (psoriasis) Rare genetic disorder Lesch-Nyan Syndrome pharmaceuticals

61 Signs and Symptoms Acute attack: Over hours frequently nocturnal Excruciating pain Swelling, redness and tenderness Podagra: 1 st MTP classic presentation May effect knees, wrist, elbow, and rarely SI and hips. Chronic: Destructive tophacous Much greater chance if untreated Rarely presents as a chronic

62 Systemic Lupus Erythematosis Systemic Disorder, involving multiple organs in multiple ways Women:Men= 9:1 Peak Age of Onset 20 s & 30 s Incidence has tripled since 1970 s to 5.56/100,000 population

63 Systemic Lupus Erythematosus

64 What Causes SLE Cause is unknown Possible factors Genetic Environmental

65 What Happens? Loss of self-non-self recognition Diversification of antigen-driven responses Hyperactivity of T & B Cells Formation of immune complexes Type III hypersensitivity reaction

66 Osteoarthritis