PATHOLO BASIC MEDICAL PATHOLOGY (LECTURE)
TERM 2, A.Y. 2024-2025 SECOND LONG EXAMINATION
LECTURE 3
THE MUSCULOSKELETAL SYSTEM
Overview on the Musculoskeletal System
Bone
● Calcified connective tissue consisting of osteocytes; 206 in adult human body Bone Matrix seen in Woven and Lamellar Bone
● Extracellular Matrix + Specialized Cells
Cells
1 Osteoprogenitor ● Give rise to osteoblasts
cells
2 Osteoblasts ● Synthesize, transport and assemble matrix
● Respond to calcitonin
Compact/Lamellar Bone Trabecular/Cancellous/Spongy Bone Calcitonin ● Increases calcium in bone
● Decreases calcium in blood
Function of Bone 1. Support 3 Osteocytes ● Maintain calcium-phosphate balance
2. Transmission of forces
3. Protection 4 Osteoclasts ● Respond to parathyroid hormone
4. Homeostasis
5. Hematopoiesis Parathyroid ● Increases calcium in blood
hormone ● Decreases calcium in bone
Forms of Bone Woven Bone ● Physiologic in early life
● Pathologic in adults
● Immature
Lamellar Bone ● Mature
Matrix
● Extracellular component of bone
● Composed of
○ Organic component: Type I Collagen
○ Mineral component
● Produced by osteoblasts
● ‘Hardness’ imparted by calcium hydroxyapatite
(L→R) Osteoblasts lining the rim of bone; Bone remodelling through the action of
Osteoclasts; Normal Adult Bone
BASIC MEDICAL PATHOLOGY (LECTURE) | SECOND LONG EXAMINATION 1
, PATHOLO TERM 2, A.Y. 2024-2025
Parts of a Bone Developmental Disorders of Bone and Cartilage
Diaphysis ● Forms the shaft Diseases caused by / associated with defects in…
● Composed of compact bone
○ Encloses the marrow cavity 1 Defects in Nuclear and Transcriptional Factors
Metaphysis ● Part of diaphysis ● Most common mutations in
● Growth zone ○ The homeobox HOXD13 gene
○ RUNX2 gene
Epiphysis ● Separated from the shaft by the epiphyseal plate ● Congenital absence of a bone
● Composed of spongy bone ● Patients present with
○ Polydactyly – more than 5 fingers
Modeling and Remodeling ○ Syndactyly – wholly or partially fused fingers or toes
○ Aplasia – congenital absence of bone
● Modeling – growth and enlargement of skeleton ○ Craniorachischisis – anencephaly with a contiguous bony defect of the spine
● Remodeling – breakdown and renewal of bone
● Bone Mass
○ Peak: Achieved by early 20s
○ Decreased by 40 years old (Bone Resorption > Bone Formation)
● Nuclear Factor κB (NF – κB) Pathway
○ Activated NF – κB Pathway → Increased osteoclast activity → Bone resorption
○ Overactivation of NF – κB Pathway = Degenerative Bone Disease
2 Defects in Hormones and Signal Transduction
Active growth plate; (1) Reserve Zone, (2) Zone of ● Two main types
Proliferation, (3) Zone of Hypertrophy, (4) Zone of 1. Achondroplasia
Mineralization, (5) Primary Spongiosa ➔ Major cause of dwarfism
➔ Cased by gain-of-function mutations in FGF receptor 3 (FGFR3)
➔ Normally, FGFR3 INHIBITS endochondral growth
➔ Gain-of-function mutation → activated FGFR3 → growth suppression
2. Thanatophoric Dysplasia
➔ Most common lethal form of dwarfism
BASIC MEDICAL PATHOLOGY (LECTURE) | SECOND LONG EXAMINATION 2
TERM 2, A.Y. 2024-2025 SECOND LONG EXAMINATION
LECTURE 3
THE MUSCULOSKELETAL SYSTEM
Overview on the Musculoskeletal System
Bone
● Calcified connective tissue consisting of osteocytes; 206 in adult human body Bone Matrix seen in Woven and Lamellar Bone
● Extracellular Matrix + Specialized Cells
Cells
1 Osteoprogenitor ● Give rise to osteoblasts
cells
2 Osteoblasts ● Synthesize, transport and assemble matrix
● Respond to calcitonin
Compact/Lamellar Bone Trabecular/Cancellous/Spongy Bone Calcitonin ● Increases calcium in bone
● Decreases calcium in blood
Function of Bone 1. Support 3 Osteocytes ● Maintain calcium-phosphate balance
2. Transmission of forces
3. Protection 4 Osteoclasts ● Respond to parathyroid hormone
4. Homeostasis
5. Hematopoiesis Parathyroid ● Increases calcium in blood
hormone ● Decreases calcium in bone
Forms of Bone Woven Bone ● Physiologic in early life
● Pathologic in adults
● Immature
Lamellar Bone ● Mature
Matrix
● Extracellular component of bone
● Composed of
○ Organic component: Type I Collagen
○ Mineral component
● Produced by osteoblasts
● ‘Hardness’ imparted by calcium hydroxyapatite
(L→R) Osteoblasts lining the rim of bone; Bone remodelling through the action of
Osteoclasts; Normal Adult Bone
BASIC MEDICAL PATHOLOGY (LECTURE) | SECOND LONG EXAMINATION 1
, PATHOLO TERM 2, A.Y. 2024-2025
Parts of a Bone Developmental Disorders of Bone and Cartilage
Diaphysis ● Forms the shaft Diseases caused by / associated with defects in…
● Composed of compact bone
○ Encloses the marrow cavity 1 Defects in Nuclear and Transcriptional Factors
Metaphysis ● Part of diaphysis ● Most common mutations in
● Growth zone ○ The homeobox HOXD13 gene
○ RUNX2 gene
Epiphysis ● Separated from the shaft by the epiphyseal plate ● Congenital absence of a bone
● Composed of spongy bone ● Patients present with
○ Polydactyly – more than 5 fingers
Modeling and Remodeling ○ Syndactyly – wholly or partially fused fingers or toes
○ Aplasia – congenital absence of bone
● Modeling – growth and enlargement of skeleton ○ Craniorachischisis – anencephaly with a contiguous bony defect of the spine
● Remodeling – breakdown and renewal of bone
● Bone Mass
○ Peak: Achieved by early 20s
○ Decreased by 40 years old (Bone Resorption > Bone Formation)
● Nuclear Factor κB (NF – κB) Pathway
○ Activated NF – κB Pathway → Increased osteoclast activity → Bone resorption
○ Overactivation of NF – κB Pathway = Degenerative Bone Disease
2 Defects in Hormones and Signal Transduction
Active growth plate; (1) Reserve Zone, (2) Zone of ● Two main types
Proliferation, (3) Zone of Hypertrophy, (4) Zone of 1. Achondroplasia
Mineralization, (5) Primary Spongiosa ➔ Major cause of dwarfism
➔ Cased by gain-of-function mutations in FGF receptor 3 (FGFR3)
➔ Normally, FGFR3 INHIBITS endochondral growth
➔ Gain-of-function mutation → activated FGFR3 → growth suppression
2. Thanatophoric Dysplasia
➔ Most common lethal form of dwarfism
BASIC MEDICAL PATHOLOGY (LECTURE) | SECOND LONG EXAMINATION 2
