Selection of NSAID

Mild/Moderate Pain• Paracetemol
• Low dose Ibuprofen
Post op. or short lasting pain• Ketorolac, diclofenac
Musculoskeletal pain• Paracetemol
• Ibuprofen, naproxen, ketoprofen
RA,AS,Acute gout, Acute Rh. fever• Naproxen, piroxicam
• Indomethacin, high dose aspirin
GI irritation• Paracetemol
• Cox-2 inhibitors
H/O HS reaction to NSAIDs• Paracetemol/
• Cox-2 inhibitors
Paediatric pt.• Paracetemol, Ibuprofen & naproxen
Pregnancy• Paracetemol
Selection of NSAID

Dentowesome 2020|@drmehnaz 🖊

Anatomic Divisions and Terms

The 206 bones of the body divide into two major groups

  • Axial bones – comprise the vertical axis of the skeleton; 80 bones.
  • Appendicular bones – bones that append (aka attach) to the axial skeleton; 126 bones.

Anatomical position

  • The vertebral column is vertical, the arms are extended with palms facing anteriorly, and the legs are extended with toes pointing anteriorly (towards the front of the body).

Axial skeleton

Skull

  • Encloses and protects brain

Hyoid bone

  • U-shaped bone; muscles of speech and swallowing attach to the hyoid bone

Vertebral column

Bones of the spine, terminates in the sacrum

Thoracic cage

  • Sternum – breast bone
  • Ribs – form the lateral walls of the thoracic cage

Appendicular skeleton

Pectoral girdle

  • Comprises the scapula (aka shoulder blade), which articulates with the humerus; and, the clavicle, which articulates with the sternum and scapula

Arm

  • The humerus articulates with the scapula

Forearm

  • The radius (laterally)
  • The ulna (medially)

Hand

  • Carpals (wrist)
  • Metacarpals (palm)
  • Phalanges (fingers)

Pelvic girdle

  • Bilateral os coxa bones (aka hip bone), articulate with the sacrum posteriorly

Thigh

  • Femur (aka thigh bone) articulates with the lateral side of the coxal bone; it is the longest and strongest bone in the body

Leg

  • Fibula, laterally; very slim, attachment site for muscles
  • Tibia, medially (“shin” bone); thick, weight-bearing bone of the leg

Kneecap

  • Patella; encased within tendons that pass over the knee, so is a sesamoid bone

Foot

  • Tarsals (ankle)
  • Metatarsals (foot base)
  • Phalanges (toes)

Directional nomenclature

Proximal

  • Closer to the center of the body or limb attachment

Distal

  • Further from the center of the body or limb attachment

Contralateral

  • On opposite sides of the body

Ipsilateral

  • On same side of the body

Intermediate

  • A structure between two others

Superior

  • Towards the top of the head

Inferior

  • Towards the feet

Medial

  • Towards the midline of the body

Lateral

  • Away from the midline of the body

Sagittal plane

  • Divides body into right and left sides

Transverse plane

  • Divides body into superior and inferior divisions

Superficial

  • Structure that is close to the surface of the body

Deep

  • A structure that is near the center of the body

Bone Functions and Features

Skeletal system

  • Comprises bones, their membranous linings, and cartilage.
  • Bones are living organs; they comprise connective tissue, nervous tissue, and epithelium.

Key features of bones:

  • Crest — a narrow ridge
  • Tubercle — a small irregular projection
  • Tuberosity — a large raised, roughened bony region.
  • Spine — a sharp raised projection
  • Notch — an indentation in bone
  • Trochanters — large irregular projections
  • Line or linea — a long narrow ridge
  • Head — an enlarged region of bone
  • Fovea — a small pit
  • Condyles — rounded ends or projections of bone
  • Epicondyle — a projection above a condyle (epi = on or above)
  • Facets — smooth articular surfaces
  • Meatus — a tubular passage
  • Fossa — shallow depression
  • Groove — a long narrow depression
  • Sinus — a hollow cavity within a bone
  • Process — a bony projection
  • Fissure — a long narrow opening
  • Foramen — a round opening in the bone through which nerves or blood vessels traverse
  • Ramus — an extension of bone

Functions

  • Features that serve as projections that form joints:
    Head (femur, rib)
    Condyle (femur)
    Facet (rib)
    Ramus (skull)
  • Features that serve as projections that attach muscle/ligaments:
    Tuberosity (os coxa)
    Tubercle (os coxa)
    Crest (os coxa)
    Spine (os coxa)
    Trochanter (femur)
    Line (linea) (femur)
    Epicondyle (femur)
    Process (skull)
  • Features that serve as depressions or openings:
    Meatus (skull)
    Sinus (skull)
    Fossa (skull)
    Groove or sulcus (skull)
    Fissure (skull)
    Foramen (skull)
    Notch (os coxa, skull)
    Fontanel (membranous covering; not shown)
    Fovea (small depression; not shown)

6 Key Functions of Bone:

  • Support: Forms the framework for physical form; attachment sites for muscles and connective tissues.
  • Movement: Acts as a series of levers when muscles contract to allow movement of body.
  • Protection: Protects vital organs from injury. For example: the skull protects the brain and the thoracic cage protects the heart and lungs.
  • Mineral storage: Provides a reservoir for calcium and phosphorus.
  • Blood cell production: Hematopoiesis occurs in red bone marrow.
  • Energy storage: Lipids are stored in adipose cells of yellow marrow.

Cartilage – Biology and Development

Key points:

  • Cartilage is connective tissue with a semi-solid extracellular matrix that comprises collagen fibers and ground substance, which provides both support and protection for other body tissues.
  • Three types covered here: hyaline, fibrous, and elastic.

Hyaline cartilage

  • Most abundant type of cartilage in the body.
  • Hyaline cartilage forms most of the fetal skeleton and is important in endochondral bone growth until the end of adolescence.
  • In the adult, it persists in the nose, trachea, and larynx, thorax, and also covers the articular surfaces of long bones (where it has no perichondrium).
  • Degeneration and calcification of hyaline cartilage may either be physiologic or pathologic. It is physiologic in the case of endochondral bone formation but it is pathologic in the case of osteoarthritis, which leads to pain and restricted joint movement. There are other forms of arthritis, such as rheumatoid arthritis, which is an inflammatory form of arthritis in which the immune system aggressively attacks the cartilage, bone, and synovial membranes of the joints
  • Calcification (the processes by which cartilage is replaced by osseous tissue) is common in hyaline cartilage, but very rare in elastic or fibrous cartilages.

Hyaline Cartilage Layers:

  • Perichondrium, outer surface
  • Matrix

Perichondrium

  • Comprises inner and outer layers (although in slow-growing or inactive perichondrium, it is not always possible to visually distinguish two separate layers).
  • Inner layer is the chondrogenic (aka cellular) layer; it comprises chondrogenic cells.
  • Outer layer it he fibrous layer; it comprises Type I collagen fibers, blood vessels, which supply nutrients to the cartilage below, and, fibroblasts, which are thought to produce collagen fibers and/or chondroblasts (although intertextual variation exists regarding this point).

Matrix

  • Appears glass-like under the microscope.
  • Is basophilic and stains purple on H & E section
  • Contains territorial matrixes that comprise the proteoglycan-rich, dark staining area around the lacunae.
  • Ground substance of the matrix, which is gel-like, comprises the following components:
    Proteoglycan aggregates, which are bound to collagen fibrils, and which provide a semi-solid structure to cartilage,
    Chondronectin, which adheres collagen fibers to chondrocytes, and,
    Itercellular Water, which is 60-80% of net weight of the cartilage (varies by location).
  • Matrix comprises type II collagen fibers, which are invisible in standard histologic preparations.
  • Houses lacunae, which are spaces in the matrix.
  • Inside the lacunae are the chondrocytes, which are mature cartilage cells that generate and maintain the matrix.
  • Chondroblasts are derived from chondrogenic cells, and eventually mature into chondrocytes.
  • Clusters of chondrocytes are called isogenous groups.
  • Interterritorial matrix outside of the isogenic groups; it stains lightly.

Elastic Cartilage

  • Also known as yellow fibrocartilage.
  • Shares many similarities to hyaline cartilage (for instance, it also has perichondrium and contains invisible type II collagen fibers within the matrix).
  • Helpful distinguishing feature of elastic cartilage are its interwoven elastic fibers, which provide flexibility.
  • Elastic cartilage provides flexibility and resistance to permanent deformation.
  • Present in the external ear, the auditory (Eustachian) tube, and the epiglottis.

Fibrous Cartilage

  • Also shares many similarities with hyaline cartilage
  • Two helpful distinguishing features are its lack of perichondrium and its rows of chondrocytes that have type I and type II fibers in between them.
  • The bundles of type 1 and type II collagen fibers provide strength and durability for shock absorption.
  • The matrix is dense and contains relatively little ground substance.
  • The type of joint and person’s age determine the relative proportions of these two collagen fiber types within the fibrous cartilage.
  • NO perichondrium is present in fibrous cartilage.
  • Fibrous cartilage is found, most notably, in intervertebral discs, pubic symphysis, menisci of the knee, and tendons where properties of stress resistance are particularly important.

Formation and Growth of Cartilage

  • Two types of growth:
    Interstitial and appositional growth; both types occur simultaneously during early development; the relative rate of each type of growth determines the shape and structure of the cartilage.

Interstitial growth:

  • Interstitial growth occurs during early stages of cartilage formation, and in the growth plates and articular cartilages of growing long bones.
  • Cells divide within matrix to produce daughter cells that secrete their own matrix.

Appositional growth

  • New matrix forms at the periphery of the cartilage.
  • Chondrogenic cells in perichondrium differentiate to become chondroblasts
  • Chondroblasts secrete new matrix, eventually become chondrocytes.
  • Older chondrocytes remain active and maintain matrix.

Clincal Correlation:

Hyaline cartilage that has been only nominally damaged can slowly repair itself via appositional growth, but severely damaged cartilage is often replaced by tougher, more fibrous connective tissue.

Lastly, let’s address specific hormones that impact the growth of hyaline cartilage.
Denote that the following hormonal substances stimulate cartilage histogenesis: thyroxine, testosterone, and somatotropin.
Denote that the following hormonal substances inhibit cartilage histogenesis: cortisone, hydrocortisone, and estradiol.
For reference, consider how the following nutritional states affect bone growth:
Hypovitaminosis A diminishes the thickness of epiphyseal plates; decrease in growth rate.
Hypervitaminosis A accelerates ossification of epiphyseal plates; short stature (dwarfism).
Hypovitaminosis C inhibits matrix production and distorts cartilage columns in epiphyseal plates (bones are weak, repair of fractures obstructed; scurvy develops)
Hypovitaminosis D inhibits calcification of matrix, causing softening of the bones (osteomalacia); in children, growing bones become bowed (rickets)

Bone Growth

BONE GROWTH

  • Bone growth at the epiphyseal growth plate is endochondral (aka interstitial) is linear.
  • Bone growth that is periosteal (aka appositional) is via thickening (widening).

ENDOCHONDRAL OSSIFICATION

Hyaline cartilaginous model (template).

  • The diaphysis is the shaft.
  • The epiphyses are the articulating ends of the long bone.
  • The metaphyses separate the diaphysis and epiphysis.
  • The medullary cavity forms as the primary ossification center, degenerates, cavitates and remodels via interstitial growth. Endochondrium delineates it – which forms a layer of lamellar bone and osteoprogenitor cells.
  • The marrow cavity is filled with hematopoetic marrow (which comprises red and white blood cell precursors)
  • Vasculature invades the cavity to fill it with marrow.

EPIPHYSEAL GROWTH PLATE

Reserve zone

  • Filled with typical fetal hyaline cartilage cells, responsible for growth in length – these cells “lead the growth pack,” in essence.

Proliferative zone

  • Filled with chrondrocytes that proliferate but do NOT hypertrophy, regulated by Indian hedgehog – this prevents the growth plates from inactivating until puberty when the child reaches full growth the growth plates degenerate to epiphyseal lines.

Hypertrophic zone

  • Filled with hypertrophic chondrocytes (we can identify their nuclei and lipid droplets) – they undergo apoptotic enlargement and are the future site of ossification (bony matrix extension).
  • They mineralize the surrounding cartilage, attract vasculature via VEGF (vascular endothelial growth factor), and that vasculature then recruits chondroclasts to degrade the carilage and form osteoblasts, which secrete the osteoid (bony matrix).

Vascular Invasion.

HISTOLOGICAL SLIDE

From epiphysis to diaphysis, we label the…

  • Reserve zone (filled with fetal hyaline cartilage cells)
  • Proliferative zone (filled with mitotically active chondrocytes)
  • Hypertrophic zone (which undergo apoptotic enlargement)
  • Zone of vascular invasion (which provides the osteoprogenitor cells for bone proliferation).

PERIOSTEAL (APPOSITIONAL) GROWTH

From central to external…

  • The hematopoetic marrow of the marrow cavity.
  • The endosteum, which delineates the marrow cavity, itself.
    -The endosteum comprises the inner circumferential lamellae, which distinguishes this inner bony layer from the compact bone external to it.
    -The osteoprogenitor cells that line the endosteum and form the lamellae that derive the spongy bone that form the trabecular meshwork of the primary ossification center.
  • External to the endosteum, lies layer of compact bone, which, namely, comprises osteons that encompasses circular layers of lamellae around a Haversian (aka central) canal.
  • We show, for reference, an osteocyte trapped between lamellae.
  • A collagenous layer of periosteum surrounds the compact bone.
  • Periosteum divides into an outer, collagenous layer, and inner, osteogenic layer.
  • Osteoblasts from the periosteum create new osteons along the longitudinal grooves and ridges within what is referred to as the outer circumferential lamellae: it forms concentric osteons (with Haversian canals), and it also forms interstitial lamellae, which fill the spaces between osteons.
  • The inner circumferential lamellae thickens, as well.

HISTOLOGICAL SLIDE: BONE MATRIX

From marrow to periosteum, label the…

  • Hematopoetic marrow
  • Inner circumferential lamellae
  • Osteon within the compact bone (indicate its Haversian canal).
  • Periosteum external to the compact bone.
  • An osteon in the process of being formed – In time, bone matrix will be released and the deep pink of the bony matrix would be observed as this region of growth takes on a biology of bone matrix.

BONE MATRIX

  • principal inorganic substance (mineral) is hydroxyapatite, which is hydroxylated calcium/phosphate. Other constituents include magnesium, potassium, sodium, bicarbonate, and citrate.
    The principal organic substances are collagen type 1 fibers and ground substance.

Bone Histology

HISTOLOGY OF BONE

GROSS STRUCTURE

  • The diaphysis is the shaft and notably comprises the marrow cavity.
  • The metaphyses comprises spongy bone.
  • The epiphyses, which are the ends – the sites of articulation.

The epiphyseal line (the ultimate regression of the growth plate) separates the epiphysis and metaphysis.

COLLAGENOUS STRUCTURES

  • Articular cartilage are derived from hyaline cartilage, at its ends.
  • Periosteum, along the shaft, is derived from a condensation of outer connective tissue. It comprises an external layer of collagens fibers and vasculature and an internal layer of osteoprogenitor cells.
  • Endosteum, centrally, is derived from derived from a condensation of inner connective tissue and helps separate the marrow cavity, internally, from the compact bony matrix that encapsulates it. It comprises an inner circumferential lamellae and osteoprogenitor cells.

MARROW CAVITY

  • Filled with hematopoetic marrow (red blood cell and white blood cell precursors) and fatty marrow (adipose tissue).

We learn about hematopoetic marrow further elsewhere. It comprises stem cells, which can self-renew, committed precursor cells, and cells that are in the process of maturation.

BONE TISSUES

  • The medullary cavity comprises spongy bone.
  • The outer layers of the diaphysis comprises compact bone.

MICROSCOPIC STRUCTURE OF BONE (ALONG THE DIAPHYSIS)

The periosteum.

  • Internal to it, lie columns of compact bone, called osteons.
  • Centrally, within the osteons, run the Haversian (aka central) canals, in parallel.
  • Volkman’s (aka perforating) canals run in perpendicular to them.
  • These canal systems form channels for the neurovasculature.
  • The osteon comprises concentric rings of lamellae – the bone connective tissue.
  • Osteocytes are a mature form of osteoblast (the bone-producing cells) within the bony matrix; they are concentrically arranged in between the circles of lamellae. They lie within lacunae (cavities) that interconnect via canaliculi (which are spindly, like spider legs) and through which the osteocytic cytoplasmic cell processes connect for the transportation of nutrients and waste.
  • The outer layer forms the cement line.
  • Interstitial lamella lie in between the osteons, which comprises remnants of partially resorbed osteons.
  • Sharpey’s fibers are collagenous fibers that anchor the periosteum to the outer lamellae.

Endosteum

  • Lies internal to the compact bone. It comprises:
    -An inner-circumferential lamellae
    -Osteoprogenitor cells
  • Spongy bone lies internal to the endosteum and comprises a network of lamellae that do NOT form the Haversian channels and osteons found in compact bone.

HISTOLOGICAL SLIDES

Compact bone

  • Osteon
  • Haversian (aka central) canal
  • Interstitial lamella
  • Osteocyte within a lacuna

Osteon (at higher resolution)

  • Concentric pattern of lamellae (the bony layer).
  • External to this lamella, show a lacuna.
  • Canaliculi radiate from it
  • Haversian canal
  • Edge of a Volkman’s canal, which perforates it perpendicularly.

Marrow cavity

  • Inner circumferential lamellae of the endosteum
  • Hematopoetic marrow
  • Fatty marrow, which increases with age
  • Vascular sinusoid