Normal Bone, Joint Histo, Congenital Disorders - Gupta Flashcards
At what decade does bone resorption start to exceed bone formation
4th decade
Bone primarily composed of what 2 components?
- Type 1 collagen (osteoid)
- Hydroxyapatite
Name the 3 cells found in bone?
Osteoblasts, Osteoclasts, Osteocytes
Hydroxyapatite (bone) is main storage of what ions?
Calcium (99%), Phosphorus (85%), Sodium and Magnesium (65%)
% = total of body storage
Osteoblast function?
synthesize bone
Osteoclast function?
Resorb bone
Osteocyte function?
maintain bone
What are howship lacunae?
Pits created by osteoclast activity, indicating bone is undergoing resorption
Osteoclasts are derived from the same stem cells that produce ____?
macrophages
RANK ligand is found on what cells?
Stromal cell/osteoblast
RANK is found on what cells
Osteoclasts precursors
If RANK-ligand and RANK bind, what occurs next?
Osteoclast precursor cells are stimulated to produce NF-kB, causing the osteoclast precursor to differentiate into a active osteoclast
In addition to RANK-ligand, what other stimulatory cytokine is present on osteoblasts? What is its function?
Macropahge colony stimulating factor (M-CSF), similar function as RANK-L/RANK binding, will stimulate NF-kB production by osteoclast
Osteoprotegerin binds with RANK or RANK-Ligand? What happens when it binds?
Osteoprotegerin (OPG) binds with RANK-ligand (on osteoblasts) preventing binding of RANK, thus inhibiting NF-kb production and osteoclast differentiation.
Epiphyseal plate made of what 3 components?
Periosteum, bone marrow, residual cartilage
What are the 2 types of ossification?
Enchondral, Membranous
Which type of ossification occurs at epiphyseal plates?
ANS: Enchondral
Membranous occurs in cranial bones and everywhere there is periosteum
Which type of ossification occurs through a cartilage intermediate step?
Enchondral
Membranous does not require cartilage intermediate step. Cells from the periosteum differentiate into osteoblasts and make bone
Which type of ossification is involved in fracture healing.
Trick question. Both are involved.
What are the 2 types of bone in terms of characteristics? Vague question. I know
Lamellar bone, Woven bone
Which type of bone (lamellar or woven) is produced following a fracture?
Woven bone
Which type of bone (lamellar or woven) is stronger?
Lamellar bone
Describe how woven bone looks?
Coarse with random orientation.
In lamellar bones, what structure(s) run longitudinally, communicating with medullary cavities? Communication via what structure
Osteons (haversian systems) communicate with medullary cavity by volkmann’s canals
Osteogenesis imperfecta is a group of genetic disorders caused by a defect in ?
defect in synthesis of Type 1 collagen
Mode of inheritence in OI?
Autosomal dominant
Mutations underlying OI involve the coding sequences for which chains of Type 1 collagen?
alpha 1 or alpha 2
Besides the bones being affected in OI, what other manifestations are common? Why is this?
Skin, joints, teeth, and eyes are just some areas involved, bc Type I collagen (which is defective in OI) is a major component of extracellular matrix in multiple parts of the body
Blue Sclerae is associated with which type of OI?
Type I
Type I OI. Lifespan?
Normal lifespan
Type 1 OI. Fracture proclivity (likelihood)
Modestly increased until puberty. then it decreases
Type 1 OI. Why the blue sclera?
Decreased collagen content of sclera allows the underlying choroidal veins to be visible
Hearing loss seen in Type 1 O1. Why?
Conduction defects in the middle and inner ear bones
Small, misshapen teeth can be seen in Type 1 OI. Why?
Dentin deficiency
Which OI type is associated with perinatal lethality?
Type II. Uniformly fatal in utero or immediately after birth as a consequence of multiple fractures that occur before birth
What is the most common form of dwarfism?
Achondroplasia
What mental deficits are seen in achondroplasia?
None. Think of tyrion lannister. “A lannister always pays his debts”
Achondroplasia caused by what mutation? Describe what this mutation does?
Activating (point) mutation in fibroblast growth factor receptor-3 (FGFR3)
FGFR3 - typically inhibits cartilage proliferation. In disease, FGFR3 turned on constantly, suppressing cartilage growth
What form of dwarfism is associated with a lethal variant? Why do they die?
Thanatophoric dwarfism, small thorax leads to respiratory complications and death
Mode of inheritance in Achondroplasia?
Autosomal dominant or new spontaneous mutation in 80% of cases
Achondroplasia affects all bones that ___?
develop by echondral ossification. That is why the head is normal size in these patients.
Osteopetrosis is associated with a deficiency in ?
defiency in osteoclast activity/function, causes overgrowth and sclerosis of cortical bone (“too much bone”)
Osteopetrosis is both autosomal dominant and autosomal recessive. Which form is more severe?
Autosomal recessive (more severe) lethal.
Autosomal dominant is considered adult form with mild clinical manifestations.
Osteopetrosis is associated with a deficiency of what enzyme? Consequence of this? What other organ could be affected as a result of this?
Carbonic anhydrase II deficiency = cant form acidic microenvironment needed for bone resorption = can’t break down hydroxyapatite
Renal tubular cells also require CA2. Without it, renal tubular cells cannot acidify urine. ALSO, decreased tubular resoprtion of HCO3-, leading to metabolic acidosis
Metabolic acidosis is associated with which congenital disorder. Why?
Osteopetrosis, Carbonic anhydrase II mutation prevents renal tubular cells from acidifying urine and reabsorping HCO3-, causing metabolic acidosis
Besides renal tubular acidosis, what other clinicial features are associated with osteopetrosis (3)?
- Fractures
- Anemia, thrombocytopenia, and leukopenia (due to loss of medullary cavity), with extra medullary hematopoiesis (such as spleen or liver)
- Hydrocephalus - narrowing of foramen magnum
Definition of rickets?
Accumulation of unmineralized bone matrix
Rickets is associated with a disturbance in ___? What 3 mechanism of disturbance?
Vitamin D. Either defiency of Vit D, abnormal metabolism of Vit D, or calcium deficiency
Vitamin D helps do what in both flat and long bones?
Vit D helps mineralize osteoid matrix and epiphyseal cartilage in both flat and long bones.
Vitamin D also stimulates osteoblasts to synthesize what? What is its purpose?
Stimulates osteoblasts to synthesize osteocalcin, a Ca2+ binding protein involved during bone development
What 4 clinical features can be seen in Rickets?
Pigeon Chest deformity, Rachitic rosary, Frontal bossing, bowing of the legs
Microscopically, what can be seen in rickets?
non-calcified, hypertrophied growth plate, particulary on metaphyseal side. Wide osteoid seams
