MUSCULOSKELETAL SYSTEM AND LABORATORY DIAGNOSIS

Dr. Arief Indra Sanjaya, SpPK

Structure and function of bone

Main function of the bony skeleton Structural support Protection of internal organs Hematopoiesis Metabolic (reservoir of calcium)

Cell types in bone

Osteoblasts

Mononuclear cells derived from bone marrow stromal cell Synthesize bone matrix Osteoblast that have become trapped within the bone trabeculae and have ceased to synthesize bone matrix Multinucleated and are derived from mononuclear phagocyte system Responsible for bone resorption

Osteocytes

Osteoclasts

Picture bone composition

Bone biochemistry

Bone is constantly remodelled and reformed by Bone Remodelling Unit

Osteoclastic bone resorption Osteoblastic synthesis of organic matrix Mineralization of the matrix

Important factors: Calcium, Phosphate, Parathyroid hormone, Alkaline phosphatase, Magnesium

Calcium

Function:

Regulation of cell function in determining activity of enzymes Activates contraction of myosin fibril in muscle Control secretion of several endocrine glands eg: parathyroid glands, thyroid C cells, pancreatic beta cells

Calcium

Requirements depend on: age, growth, pregnancy and lactation Plasma calcium concentration is controlled by:

Parathyroid hormone (PTH) Calcitonin 1,25 dihydroxycholecalciferol (DHCC)

Factors affecting absorption of dietery calcium: gut pH, fat absorption, Ca/phosphate ratio, oxalates

Phosphate

Intracellularly:

Integral component of phospholipid and phosphoproteins Inorganic phosphate (small fraction but important) high-energy transfer reaction

Extracellularly: hydroxyapatite In the plasma/serum most phosphate is inorganic

Parathyroid hormone (PTH)

Produced by parathyroid glands Its release is stimulated by:

Hypocalcemia, hypomagnesaemia, prostaglandin, cathecolamine, hydroxy vitamin D metabolites Enhancing bone resorption Enhancing reabsorption of calcium

Maintain plasma calcium homeostasis by:

Alkaline phosphatase

The reachest sources of alkaline phosphatase:

Osteoblasts in bone Bile canaliculi in the liver Small intestinal epithelium Placenta Proximal tubule in kidney Breast in lactation

Function: phosphate transport across cell membranes

Magnesium

Kidney is principal organ of Mg homeostasis 60% reabsorption occurs in the thick ascending loop of Henle and 20-30% in the proximal tubule No hormones or factors are involved in the control of renal handling

Congenital Desease of Bone

Achondroplasia

Autosomal dominanb Shortening of limbs Autosomal pattern Defective synthesis of collagen by fibroblasts and osteoid bu osteoclasts Bone fragility, hernia, blue sclera and thin skin Very rare, two forms Mild autosomal dominant Lethal autosomal receive

Osteogenesis imperfecta (brittle bone disease)

Osteopetrosis (marble bone disease)

Metabolic bone disease

Osteoporosis Rickets and osteomalacia Renal osteodystrophy Bone lesions in primary hyperparathyroidism Pagets disease of bone (osteitis deformans)

Picture mechanisms of bone mass regulation

Osteoporosis

Decreased bone mass with a normal ratio of mineral to organic matrix Result from imbalance between bone production by osteoblasts and bone resorption by osteoclasts Normal feature of ageing seen in elderly patients Other causes of generalized osteoporosis: endocrine disease, liver disease Localized osteoporosis: immobilization, pagets disease & infiltration of bone by tumour

Rickets and osteomalacia

Deficient mineralization of the organic bone matrix; the amount of bone is normal Rickets occurs in children, osteomalacia in adult Etiology:

Vit D deficiency Renal disease Anticonvulsant therapy

Pagets disease of bone (osteitis deformans)

Unknown etiology Increased osteoclastic and osteoblastic activity May be asymptomatic Disease activity is best assessed by:

increase serum alkaline phosphatase Increase hydroxyproline Serum calcium and phosphate usually normal

Bone infections

Acute osteomyelitis

Most common cause: Staphylococcus aureus Hot, painful bony lession with fever Culture from bone biopsy Follow inadequately treated acuted disease or indolent infection (eg: tuberculosis)

Chronic osteomyelitis

Bone tumors

Primary bone tumours are rare neoplasms Diagnosis: combination from

Clinical history & examination X-ray Histophatology Laboratory examination: PTH, alkaline phosphatase level, white cell count, etc.

Commonest metastases from primary sites: breast, thyroid, bronchus, kidney

Joint structure

Joint may be freely mobile, permit slight movement or fixed and rigid Synovial membrane is lined by two types of cell: type A are phagocytic and type B are fibroblastic and secrete hyaluronic acid and other proteins of synovial fluid

Synovial fluid

= joint fluid Ultrafiltrate of the plasma across the synovial membrant into which a mocopolysaccharide containing hyaluronic acid & small amount of protein is secreted by the cell of the synovial membrant Supply the nutrients to the cartilage & act as a lubicant to the surface of the frequently moving joints

Picture joint

Specimen collection

Normal: <3,5 mL Arthrocentecis 3 tubes:

1. sterile heparinized for microbiology 2. anticoagulated for hematology 3. non anticoagulated for other test

Examination & report macroscopic

Appearance

Normal: clear & pale yellow Deeper yellow: inflammation Greenish tinge: bacterial infection Blood: hemorrhagic arthritis ec. traumatic aspiration Turbid: cell count elevated Milky: presents of crystals

macroscopic

Viscosity

Polymerization of hyaluronic acid Arthritis affects production & polymerization viscosity of fluid

String test

Normal: 4-6 cm Bedside test

macroscopic

Mucin clot test

Measure the degree of hyaluronate polymerization Synovial fluid + 2-5% acetic acid sol. solid clot surrounded by clear fluid Report: good (solid clot) Fair (soft clot) Poor (friable clot) Very poor (no clot)

Classification & pathologic significance of joint disorders

Group classification Pathologic significance

I. Noninflammatory II. Inflammatory

III. Septic IV. Crystal induced V. Hemorrhagic

Degenerative joint disorders Immunologic problems, including RA & SLE Microbial infection Gout Pseudogout Traumatic injury Coagulation deficiencies

Microscopic

Cell count

WBC count: immediately

Decrease rapidly after 1 hour !

Normal: < 200 cells/uL Methodology:

Improved Neubauer Counting chamber

Normal saline as a diluent

Microscopic

Differential count

Thinly smeared Wright stainted slide Normal: PMN < 25% MN: lymphocytes, monocytes, macrophages, synovial tissue cells PMN: septic condition Lymphocyte predominance: nonseptic imflamation

Microscopic

Crystal identification

Soon after the fluid is colected because temperature & pH will affect crystal solubility Monosodium urate (uric acid) gout Calcium pyrophosphate pseudogout Cholesterol crystal Crystals of apatite

Chemistry

Value of chemistry test = its value in serum Glucose: Inflammatory disorders Septic disorders Total protein normal: < 3 g/dL

: inflammatory & hemorrhagic disorders

uric acid: gout

Microbiology

Identify the organisms causing septic inflammation Bacterial inflammation are most frequent Gram staint Culture

Serology

Autoimmune disease

Rheumatoid arthritis Systemic Lupus Erythematosus

As a confirmatory measure in cases that are difficult to diagnose

Summary laboratory findings in joint disorders

Group classification Laboratory findings I. Noninflammatory Clear, yellow fluid Good viscosity WBCs < 2000, neutrophils < 30% Normal glukose Cloudy, yellow fluid Poor viscosity WBCs 2000-5000, neutrophils > 50% Decrease glukose Possible autoantibodies + Cloudy, yellow-green fluid Poor viscosity WBCs 10.000-200.000, neutrophils > 90% Decreased glucose Positive culture & Gram staint

II. Inflammatory

III. Septic

Summary laboratory findings in joint disorders

Group classification Laboratory findings IV. Crystal induced Cloudy or milky fluid Poor viscosity WBCs up to 50.000, neutrophils < 90% Decrease glucose Elevated uric acid Crystals + Cloudy, red fluid Poor viscosity WBCs < 5.000, neutrophils < 50% Normal glucose RBCs present

V. Hemorrhagic