STRUCTURE AND FUNCTION OF BONE, JOINTS AND CONNECTIVE TISSUE - PowerPoint Presentation

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STRUCTURE AND FUNCTION OF BONE, JOINTS AND CONNECTIVE TISSUE

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CLASSIFICATION OF JOINTS

Human joints provide the structures by which bones join with one another and may be classified according to the

histologic

features of the union and the range of joint motion. There are three classes of joint design:

(1) synovial or

diarthrodial

joints which articulate with free movement, have a synovial membrane lining the joint cavity, and contain synovial fluid;

(2)

amphiarthroses

, in which adjacent bones are separated by

articular

cartilage or a

fibrocartilage

disk and are bound by firm ligaments permitting limited motion (e.g., pubic

symphysis

,

intervertebral

disks of vertebral bodies, distal

tibiofibular

articulation, and sacroiliac joint articulation with pelvic bones);

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3)

synarthroses

, which are found only in the skull (suture lines) where thin, fibrous tissue separates adjoining cranial plates that interlock to prevent detectable motion before the end of normal growth, yet permit growth in childhood and adolescence.

The synovial joints are classified further according to their shapes, which include

ball-and-socket

(hip),

hinge

(

interphalangeal

), saddle

(first

carpometacarpal

), and

plane

(

patellofemoral

) joints. These configurations reflect the varying functions, as the shapes and sizes of the opposing surfaces determine the direction and extent of motion.

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PRESENTING PROBLEMS IN MUSCULOSKELETAL DISEASE Pain in a single joint

Principal causes of acute

monoarthritis

in a previously normal joint

Septic arthritis

Crystal

synovitis

: gout,

pseudogout

Monoarticular

presentation of

oligo

- or

polyarthritis

Reactive, psoriatic or other

seronegative

spondarthritis

Erythema

nodosum

Rheumatoid arthritis

Juvenile idiopathic arthritis

Trauma: especially if associated with

haemarthrosis

Haemarthrosis

associated with clotting abnormality

Foreign body reaction (e.g. plant thorn)

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Oligoarthritis

Oligoarthritis

affects 2-4 joints or joint groups (the wrist has many joints but counts as a single site).

Causes of inflammatory

oligoarthritis

.

Seronegative

spondyloarthritis

Reactive arthritis

Psoriatic arthritis

Ankylosing

spondylitis

Enteropathic

arthritis

Erythema

nodosum

Juvenile idiopathic arthritis

Oligoarticular

presentation of

polyarthritis

Infection, including

Infective

endocarditis

Neisseria

Mycobacteria

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Causes of poly

arthritis

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A-Rheumatoid arthritis (symmetrical, small and large joints, upper and lower limbs).

B-

Seronegative

psoriatic arthritis (asymmetrical, large > small joints, associated

periarticular

inflammation giving

dactylitis

).

C-

Seronegative

spondyloarthritis

(axial involvement, large > small joints, asymmetrical).

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MATURE ARTICULAR CARTILAGE

Articular

cartilage is a specialized connective tissue that covers the weight-bearing surfaces of

diarthrodial

joints.

The principal functions of cartilage layers covering bone ends are to permit low-friction, high-velocity movement between bones, to absorb the transmitted forces associated with locomotion, and to contribute to joint stability.

Lubrication by synovial fluid provides frictionless movement of the articulating cartilage surfaces.

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Chondrocytes

are the single cellular component of adult hyaline

articular

cartilage and are responsible for synthesizing and maintaining the highly specialized cartilage matrix macromolecules.

The cartilage extracellular matrix is composed of an extensive network of collagen fibrils, which confers tensile strength, and an interlocking mesh of

proteoglycans

, which provides compressive stiffness through the ability to absorb and extrude water.

The cartilage is

avasculare

and

aneural

.

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Numerous other

noncollagenous

proteins also contribute to the unique properties of cartilage ,(Collagens,

Proteoglycans

, Other

Noncollagenous

Proteins (Structural), Or (Regulatory).

Proper distribution and relative composition of these proteins is required for the function of cartilage in protecting the

subchondral

bone from adverse environmental influences.

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As the single cellular component in adult

articular

cartilage,

chondrocytes

are responsible for maintaining the ECM components in a low-turnover state. The composition and organization of matrix macromolecules, unique to this tissue, are determined during

chondrocyte

differentiation in embryonic and postnatal development of cartilage.

Adult

chondrocytes

exist in a hypoxic environment within

articular

cartilage. They are inactive metabolically, partially as a result of an absence of blood vessels and nerves, and display a rounded morphology that reflects their quiescent state.

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Chondrocyte

culture models have been developed with the aim of maintaining differentiated phenotypes, characterized by the major collagen and

proteoglycan

constituents, type II collagen and

aggrecan

.

Chondrocytes

interact with specific ECM components via

integrins

,

annexins

, and CD44 on the cell surface.

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The

subchondral

bone plate beneath the calcified base of

articular

cartilage may have many effects on the cartilage above it. Its stiffness modifies the compressive forces to which

articular

cartilage is subjected, its blood supply may be important in cartilage nutrition ,and its cells may produce peptides that regulate

chondrocyte

function.

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Several studies have suggested that the responses of the

subchondral

bone to mechanical stimulation may transmit signals into the

articular

cartilage.Tidemark

advancement with thickening of the calcified cartilage and thinning of

articular

cartilage is associated with fibrillation of the cartilage surface during aging.

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Condrocyte

only 2%

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SYNOVIAL FLUID AND NUTRITION OF JOINT STRUCTURES

The volume and composition of synovial fluid are determined by the properties of the

synovium

and its vasculature.

Fluid in normal joints is present in small quantities (2.5

mL

in the normal knee) sufficient to coat the synovial surface, but not to separate one surface from the other.

Tendon sheath fluid and synovial fluid are biochemically similar. Both are essential for the nutrition and lubrication of adjacent

avascular

structures, including tendon and

articular

cartilage, and for limiting adhesion formation, maintaining movement.

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The synovial joint is uniquely adapted to responding to environmental and mechanical demands. The synovial lining is composed of two to three cell layers, and there is no basement membrane separating the lining cells from the underlying connective tissue.

The

synovium

produces synovial fluid, which provides nutrition and lubrication to the

avascular

articular

cartilage

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SYSTEMIC REGULATION OF BONE REMODELING

CALCIUM METABOLISM

Calcium is crucial to many processes in the body, including most

signaling

cascades and synaptic

signaling

, creating a requirement for tight control of systemic calcium concentrations. the skeleton is the reservoir for calcium, and bone

remodeling

is one of the processes crucial to calcium regulation. Hormones involved in calcium homeostasis have profound effects on the skeleton.

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Parathyroid hormone

The primary function of PTH is to maintain serum ionized calcium levels within a narrow physiologic range. PTH secretion increases as calcium levels decrease to less than 8 mg/

dL

, controlled by decreased binding of the calcium ion to the calcium receptor on the parathyroid

cell.When

a serum calcium value greater than 10 mg/

dL

accompanies a high level of serum PTH, a diagnosis of hyperparathyroidism can be made. Other circulating factors, such as vitamin D,

tumor

necrosis factor-α, and prostaglandins, also are involved in regulating calcium balance.

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Vitamin D

Vitamin D has effects on bone

remodeling

and calcium homeostasis. A 10-minute exposure of the skin to ultraviolet light from the sun causes endogenous production of sufficient quantities of vitamin D

3

from 7-dehydrocholesterol to allow normal calcium balance. Vitamin D

3

is first

hydroxylated

to 25-hydroxyvitamin D in the liver, followed by 25-hydroxyvitamin D hydroxylation in the kidney. Often referred to as

calcitriol

, the active metabolite, 1,25-dihydroxyvitamin D, stimulates intestinal absorption of calcium, providing the mineral necessary to build bone.

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supraphysiologic

levels induce bone

resorption

by stimulating the differentiation of

osteoclast

precursors.

This occurs through the effect of 1,25-dihydroxyvitamin D of increasing bone

stromal

cell production of M-CSF

and RANKL expression.

Besides the role of vitamin D in ensuring calcium acquisition from the intestine, vitamin D has subtle effects on the formation and

resorption

of bone.

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STIFFNESS

Stiffness is a common complaint among patients with arthritis. What is meant by stiffness varies from patient to patient, however. Some patients may use the term

stiffness

to refer to pain, soreness, weakness, fatigue, or limitation of motion.

Rheumatologists generally use the term

stiffness

to describe discomfort and limitation on attempted movement of joints after a period of inactivity. This “gel” phenomenon occurs usually after an hour or more of inactivity. The duration of stiffness related to inactivity varies, with mild stiffness lasting minutes to severe stiffness lasting hours.

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SYNOVIAL FLUID ANALYSIS

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Example on each class

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Cell Count

The WBC count and differential are among the most valuable diagnostic characteristics of SF. Normal SF contains fewer than 200 cells/mm3.

SF from

noninflammatory

arthropathies

may have WBC counts of up to 2000 cells/mm3 .

Noninfectious

inflammatory

arthropathies

have WBC counts that vary widely, ranging from 2000 to 100,000 cells/mm3 .

Although the autoimmune arthropathies

generally present with WBC counts of 2000 to 30,000 cells/mm3, cell counts of 50,000/mm3 or higher are not unusual in RA.

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Patients with crystal induced arthritis, such as acute gout, usually have WBC counts of greater than 30,000 cells/mm3 and counts of 50,000 to 75,000 cells/mm3 are common.

The closer the WBC count gets to 100,000 cells/mm3, the greater the likelihood of a septic arthritis. Although a rare patient with crystal-induced

arthropathy

, RA, or even a

seronegative

arthropathy

may have a WBC count greater than 100,000 cells/mm3, such patients should be treated empirically for a septic joint until microbiologic data exclude infection.

A WBC count of less than 100,000 cells/mm3 does not preclude the possibility of infection.