Transcript Bone Stuff - Bedford Public Schools

Part 3:
Bone Pathology
Bone Topics to Look Into
•Rickets and Vitamin D
•Dwarfism achondroplasia
•rheumatoid arthritis
•arthritis
•tendonitis
•bone marrow
•bone grafts
•bone marrow transplants
•fossil arthritis dinosaurs
•mummy X-rays
•tooth development
•tooth decay
•Neurofibromatosis “Elephant Man”
•bone cancer
•multiple myoloma
•fractures and treatment
•hip replacement
•osteoporosis
•bone mass
•thalidomide
•teratogens
Congenital Malformations: Pie Chart
albinism- autosomal recessive trait resulting in lack of pigment in skin, hair and retina.
amelogenesis imperfecta- hypocalcification leads to soft enamal on teeth. Yellow dentine is visible through the thin layer of enamal.
angiomas- vascular disorder resulting in excessive vascularisation.
dentinogenesis imperfecta-odontoblasts fail to differentiate. Enamal of teeth wears excessively.
enamal hypoplasia- environmental facors affecting ameloblast formation of enamal on teeth.
gynecomastia- stimulation by maternal sex hormones leads to excessive development of newborn male mammary glands.
ichthyosis- excessive keratinization disorder.
http://anatomy.med.unsw.edu.au/cbl/embryo/Notes/skin2.htm#abnormal
Rickets and Vitamin D
http://georgia.ncl.ac.uk/VitaminD/vitaminD.html
Bone Growth and Development and Vitamin D
When crystals of hydroxyapatite (a complex of calcium, hydroxyl and phosphate ions) are laid
down between collagen fibres, bone calcification occurs. These ions in bone are in dynamic
equilibrium with ions present in the bloodstream, an equilibrium which is regulated by
Vitamin D and by two peptide hormones, Parathyroid Hormone (PTH) and calcitonin. As late
as the 1930s and 1940s, when the role of dietary Vitamin D in normal bone growth and
development was not recognised, rickets was an all too common feature of community life,
particularly in areas with little sun exposure.
The role of Vitamin D is largely played at the site of the mucosal cells of the intestine, where
it stimulates calcium absorption and retrieval to the blood stream from food passing through
the gut, as well as in the proximal tubules of the kidney, where it promotes re-absorption of
phosphate which would otherwise be excreted in urine.
The constant turnover (dynamic equilibrium) of the ions of bone crystal between those in the
bloodstream and those stored in bone itself, is an important feature both in formation and in
repair of bone. Three types of cells work together in this process: osteoblasts, osteocytes,
osteoclasts. The osteoblasts synthesis the matrix upon which bone crystals are laid down; the
osteocytes interlink this matrix with long filaments; the osteoclasts, which sit on the surface of
bone crystals, are important in maintaining calcium and phosphate ion equilibrium with the
blood stream.
(it goes on…)
http://georgia.ncl.ac.uk/VitaminD/BoneGD.html
Neurofibromatosis
Joseph Merrick the “Elephant Man” Suffered from Either
Nuerofibromatosis or Proteus Syndrome
http://nfinc.org/noele.html
http://www.jsitton.pwp.blueyonder.co.uk/elephantman/elephant_man.htm
Proteus Syndrome: http://dermis.net/doia/diagnose.asp?zugr=d&lang=e&diagnr=9940&topic=t
Effects of Neurofibromatosis type 1 (NF-1)
Neurofibromatosis type 1 (NF-1) is an autosomal dominant
genetic disorder that causes tumors to grow on the covering
of the nerves anywhere in the body at any time. The disorder
affects 1 in 3,000 males and females of all races and ethnic
groups. The NF-1 gene is located on chromosome 17.
http://nfinc.org/nfbody1.html
Effects of Neurofibromatosis type 2 (NF-2)
Neurofibromatosis type 2 (NF-2) is an autosomal dominant
genetic disorder that causes tumors to form on the nerves
of the central nervous system, in the brain, and on the spine.
It affects one in 33,000-40,000 males and females of all
races and ethnic groups. The NF-2 gene is located on
chromosome 22.
http://nfinc.org/nfbody2.html
Teratogen and Thalidomide
Teratogen
A teratogen, also referred to as a teratogenic agent, is an environmental agent that can
cause abnormalities in a developing organism, resulting in either fetal death or congenital
abnormality. The human fetus is separated from the mother by the placental barrier, but
the barrier is imperfect and permits a number of chemical and infectious agents to pass to
the fetus. Well-known teratogens include (but are not limited to) alcohol, vitamin A and
retinoic acid in excessive doses, the rubella virus, the syphilis bacterium, and high levels
of ionizing radiation. In the 1960s, it was discovered that the tranquilizer thalidomide had
serious side effects when taken during pregnancy. Although thalidomide was never sold
legally in the United States, it was available elsewhere in the world and prescribed freely
during the 1940s and 1960s. It was later shown to induce birth defects, especially severe
limb abnormalities known as phocomelia, in children whose mothers took the drug.
http://www.findarticles.com/cf_dls/g2602/0005/2602000523/p1/article.jhtml
What is Thalidomide
Thalidomide is a drug that was introduced on to the market on October 1, 1957
in West Germany. Thalidomide soon became a drug prescribed to pregnant
women to combat symptoms associated with morning sickness. When taken
during the first trimester of pregnancy, Thalidomide prevented the proper
growth of the foetus resulting in horrific birth defects in thousands of children
around the world. These children were born in the late 1950's and early 1960's
and became known as "Thalidomide babies". See What Is Thalidomide for
more information.
http://www.ogopogo.com/thalidomide/english/index.htm
Effects of Thalidomide
•When Thalidomide was taken during pregnancy (particularly during a
specific window of time in the first trimester), it caused startling birth
malformations, and death to babies. Any part of the foetus that was in
development at the time of ingestion could be affected.
•For those babies who survived, birth defects included: deafness,
blindness, disfigurement, cleft palate, many other internal disabilities,
and of course the disabilities most associated with Thalidomide:
phocomelia.
http://www.ogopogo.com/thalidomide/english/wit.html
History of Thalidomide
Thalidomide was synthesized in West Germany in 1953 by Chemie
Grünenthal. It was marketed (available to patients) from October 1, 1957
(West Germany) into the early 1960's. Thalidomide was present in at least
46 countries under many different brand names. (See The many faces of
Thalidomide for a partial list of those names.)
Thalidomide became available in "sample tablet form" in Canada in late
1959. It was licensed for prescription use on April 1, 1961. Although
Thalidomide was withdrawn from the West German and United Kingdom
markets by December 2, 1961, it remained legally available in Canada until
March 2, 1962, a full three months later. Incredulously Thalidomide was still
available in some Canadian pharmacies until mid-May 1962.
http://www.ogopogo.com/thalidomide/english/wit.html
The pattern of thalidomide defects
The pattern of thalidomide defects
Thalidomide is associated in the public mind with limb defects, and these certainly account
for the majority of cases. However, almost any organ of the body would be affected. The
second major group of defects involves the ears, the eyes, and the nerve supplies to the face,
the eye muscles, and the lacrimal (tear) glands. Internal defects commonly affected the heart,
the kidneys and urinary tract, the alimentary tract, and the genital tract, and none was unique
to thalidomide. The early mortality rate among ‘thalidomide babies’ was about 40%, largely as
a result of serious internal malformations. Consequently, internal defects are much less
common among survivors than they were among the whole group at birth.
Most of the serious internal defects caused problems at or soon after birth which either
required treatment or led to death. Some defects of the kidneys and female genital tract which
can only be shown by special tests did not become apparent until many years after birth. It is
possible that there are still undetected internal problems in people aged 30 years or more, but
as time passes it becomes increasingly unlikely that any such hidden defects will cause
significant problems. They will therefore play little part in the diagnosis of thalidomide
damage in the future.
A small but important group of thalidomide related problems includes conditions which are
not present at birth but develop later. Abnormalities of the spine were recognized early, and of
the knees rather later. Other bones/joints may also be affected. It is to be expected that the
thalidomide damaged people will be prone to the same ills as beset the rest of the population.
A causal connection with thalidomide would be suggested if a particular disease was more
common among the thalidomide population than among the general population from which
they came, or if the disease presented at an unusual age or in an unusual way.
http://www.ogopogo.com/thalidomide/english/smithell.htm
THALIDOMIDE SURVIVORS TODAY
Giselle Cole now champions the cause for thalidomade victims.
http://www.tv.cbc.ca/witness/thalidomide/extratoday.htm
Thalidomide Children
The most common deformity suffered by children whose mothers took
thalidomide was stunted or missing arms and legs (DPA/Archive Photos)
http://more.abcnews.go.com/sections/living/thalidbkgd/
X-Rays of Shortened Limbs
Fig. 1. Photographic reproduction of a tracing of the upper
extremity roentgenograms of four patients with Thalidomide
related anomalies of the upper extremities (see Table I).
http://www.jacpoc.oandp.com/library/1994_02_051.asp
Rheumatoid Arthritis
A joint is where two bones meet to allow movement of body parts. Arthritis means joint inflammation. The joint
inflammation of rheumatoid arthritis causes swelling, pain, stiffness, and redness in the joints. The inflammation of
rheumatoid disease can also occur in tissues around the joints, such as the tendons, ligaments, and muscles. In some
patients with rheumatoid arthritis, chronic inflammation leads to the destruction of the cartilage, bone and ligaments
causing deformity of the joints.
http://www.medicinenet.com/Rheumatoid_Arthritis/page1.htm
Rheumatoid Arthritis in the Hand
The attack on a joint by the disease usually begins with the synovium. Early in the disease, edema begins to be seen in cells in
the synovium and multiplication of synovial lining cells occur. As the disease progresses, the synovium may grow
considerably larger eventually forming tissue called pannus. Pannus can be considered the most destructive element
affecting joints in the patient with rheumatoid arthritis. Pannus can attack articular cartilage and destroy it. Further,
pannus can destroy the soft subchondral bone once the protective articular cartilage is gone. The synovial fluid secreted by
the synovium is thought to serve two main purposes, lubrication of the joint and provision of nutrients to the avascular
articular cartilage. In this disease process, an interaction between antibodies and antigens occurs, and causes alterations in
the composition of the synovial fluid. Ultimately, digestants are formed in the fluid which attack the surrounding tissue. Once
the composition of this fluid is altered, it is less able to perform the normal functions noted above, and more likely to become
destructive.
http://www.duq.edu/PT/RA/EffectsOnJoints.html#Effects
Rheumatoid arthritis is an autoimmune disease
Rheumatoid arthritis is an autoimmune disease which causes chronic
inflammation of the joints. Rheumatoid arthritis can also cause
inflammation of the tissue around the joints, as well as other organs in the
body. Autoimmune diseases are illnesses which occur when the body tissues
are mistakenly attacked by its own immune system. The immune system is
a complex organization of cells and antibodies designed normally to "seek
and destroy" invaders of the body, particularly infections. Patients with
these diseases have antibodies in their blood which target their own body
tissues, where they can be associated with inflammation. Because it can
affect multiple other organs of the body, rheumatoid arthritis is referred to
as a systemic illness and is sometimes called rheumatoid disease.
http://www.medicinenet.com/Rheumatoid_Arthritis/page1.htm
Severe Rheumatoid Arthritis of the Hand
http://www.duq.edu/PT/RA/EffectsOnJoints.html#Effects
Severe Hand Deformity fromRheumatoid Arthritis
This deformity of the hand is due to rheumatoid arthritis (RA). This autoimmune disease leads to synovial proliferation and joint
destruction, typically in a symmetrical pattern involving small joints of hands and feet, followed by wrists, ankles, elbows, and knees.
Rheumatoid factor can be identified serologically in most, but not all, RA patients.
http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONE043.html
Dwarism and Achondroplasia
Achondroplasia is the most common form of disproportionate short stature.[1] The diagnosis is based on very
specific features on the radiographs, which include a contracted base of the skull, a square shape to the pelvis with
a small sacrosciatic notch, short pedicles of the vertebrae, rhizomelic (proximal) shortening of the long bones,
trident hands, a normal length trunk, proximal femoral radiolucency, and, by mid-childhood, a characteristic
chevron shape of the distal femoral epiphysis. Hypochondroplasia and thanatophoric dysplasia are part of the
differential diagnosis, but achondroplasia can be distinguished from these because the changes in
hypochondroplasia are milder and the changes in thanatophoric dysplasia are much more severe and invariably
lethal. Achondroplasia is an autosomal dominant disorder, but approximately 75% of cases represent new
dominant mutations. The gene for achondroplasia has recently been found. Achondroplasia is due to a change in
the genetic information for fibroblast growth factor receptor 3.[2,3] Almost all of the mutations have been found to
occur in exactly the same spot. Now that the gene has been found and the mutation known, potential therapies and
diagnostic methodologies are likely to be developed. A great deal is known about the natural history of the
disorder that can be shared with the family. The average adult height in achondroplasia is about 4 ft for both men
and women ( Fig 1, Fig 2, Fig 3, Fig 4, Fig 5, and Fig 6).[4] Other features include disproportionate short stature,
with shortening of the proximal segment of the limbs, a prominent forehead, a flattened midface, and an averagesized trunk. The head usually appears relatively large compared with the body. The most common complication,
occurring in adulthood, is related to lumbosacral spinal stenosis with compression of the spinal cord or nerve
roots.[5,6] This complication is usually treatable by surgical decompression, if diagnosed at an early stage.
Children affected with achondroplasia frequently have delayed motor milestones, otitis media, and bowing of
the knees ( Fig 7).[7] Occasionally in infancy or early childhood there is symptomatic airway obstruction,
development of thoracolumbar kyphosis, symptomatic hydrocephalus, or symptomatic upper cord compression.
Most individuals with achondroplasia are of normal intelligence and are able to lead independent and productive
lives.[8] Because of their disproportionate short stature, however, a number of psychosocial problems can arise.
Families can benefit from anticipatory guidance and the opportunity to learn from other families with children of
disproportionate short stature.
http://www.aap.org/policy/00696.html
Autosomal Dominant Inheritance
in Acondroplasia
As discussed above, conditions due to autosomal dominant conditions result from an
individual carrying one changed gene. Examples of autosomal dominant forms of
dwarfism include achondroplasia and hypochondroplasia. A person with
achondroplasia for example, has a 50% or 1 in 2 chance of passing the gene on to
his/her offspring.
Clues that geneticists use when looking at pedigrees to determine autosomal dominant
inheritance include the following facts:
1.
Autosomal dominant conditions are seen in every generation (vertical pattern).
2.
Males and females have the condition with equal frequency and severity.
3.
Unaffected individuals do not have children with the condition.
4.
Each child of an affected individual has a 50% chance of being affected, regardless of
sex or birth order.
5.
Homozygotes for autosomal dominant conditions (individuals with two changed genes)
have a more severe form of the disease. An example of this is the "double-dominant"
form of achondroplasia that can occur when two people with achondroplasia have
children (see below).
Autosomal Dominant Pedigree
http://www.hopkinsmedicine.org/greenberg.center/tutorial.htm#autodom
Autosomal Dominant Pedigree
http://www.hopkinsmedicine.org/greenberg.center/tutorial.htm#autodom
Key to Pedigree Symbols
Greenberg Center for Skeletal Dysplasias
http://www.hopkinsmedicine.org/greenberg.center/key.htm
Type II Collagen Conditions
Hypochondrogenesis, SED, SEMD, Kniest Syndrome
I. Introduction
Collagen is a protein that is a component of bone, cartilage, and
connective tissue. Several skeletal dysplasias (dwarfing conditions)
are due to changes in a protein called type II collagen. These include:
•hypochondrogenesis
•spondyloepiphyseal dysplasia congenita (SEDc)
•spondyloepimetaphyseal dysplasia, Strudwick (SEMD)
•Kniest dysplasia
Type 2 collagen is the major collagen of the nucleus pulposa (a
component of the spine), cartilage, and vitreous (a component of the
eye), All of these conditions therefore have common clinical and
radiographic findings including spinal changes resulting in a shorttrunked form of dwarfism, myopia, and retinal degeneration.
http://www.hopkinsmedicine.org/greenberg.center/SED.htm
Scoliosis
http://members.tripod.com/my_back/scoliosis/index.html
Gout: Xray of Foot
Chronic gout leads to deposion of urates into a chalky mass known as a "tophus". Such tophi can destroy the joint and
adjacent bone as seen here radiographically in sequential radiographs of the same foot (the patient did not have two right
feet). In most, but not all, cases there is hyperuricemia.
http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONE062.html
Sickle Cell Anemia
Sickle cells are red blood cells that have become crescent shaped. When a person with sickle cell anemia is
exposed to dehydration, infection, or low oxygen supply, their fragile red blood cells form liquid crystals and assume
a crescent shape causing red cell destruction and thickening of the blood. Since the life span of the red blood cell is
shortened, there is a temporary depression of red cell production in the bone marrow, and a subsequent fall in
hemoglobin (and therefore the resultant anemia).
http://www.wadsworth.org/chemheme/heme/microscope/sicklecell.htm
Sickle Cells - Another Picture
Severe cickling in sickle cell anemia
http://www.mcl.tulane.edu/classware/pathology/Krause/AbnormalRBC/AbnormalRBC.html
Plasma Cell Leukemia
A plasma cell is a mature B lymphocyte that is specialized for antibody (immunoglobulin) production. Plasma cells
are rarely found in the peripheral blood. They comprise from 0.2% to 2.8% of the bone marrow white cell count.
Mature plasma cells are often oval or fan shaped, measuring 8-15 µm. The nucleus is eccentric and oval in shape.
The nucleus to cytoplasm ratio is typically 2:1 to 1:1. The nucleus may be bilobed or multilobed, especially in
patients with lymphoid blood dyscrasias. The perinuclear zone is very distinct, appearing white in the deeply
basophilic cytoplasm. Nuclear chromatin is condensed and very patchy, appearing as dark blocks on a reddishpurple background. The cytoplasm stains deep blue to gray blue, depending on the stain and the ribosomal content
of the individual cell. Plasma cells are seen in multiple myeloma, plasma cell leukemia, Waldenström's
macroglobulinemia, and MGUS (monoclonal gammopathy of uncertain significance. The cells depicted in this image
are from a patient with plasma cell leukemia.
http://www.wadsworth.org/chemheme/heme/microscope/plasmacell.htm
Osteomyelitis
This is chronic osteomyelitis. Note the fibrosis of the marrow space accompanied by chronic inflammatory
cells. There can be bone destruction with remodelling. Osteomyelitis is very difficult to treat.
http://www-medlib.med.utah.edu/WebPath/BONEHTML/BONE016.html