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dr. Ahmad Fauzi, M. Epid, Sp.OT

Dept. Bedah Div. Orthopaedi dan Traumatologi
Embryogenesis :

1. The embryonic period : fertilization 8 w the body

plan is completed all major organs are established

2. The fetal period

Stem cell

An immature or undifferentiated cell which is capable of producing an

identical daughter cell
Self-renewal - the ability to go through numerous cycles of cell division
while maintaining the undifferentiated state
Potency - the capacity to differentiate into specialized cell types
In the strictest sense, this requires stem cells to be either totipotent or
pluripotent - to be able to give rise to any mature cell type, although
multipotent or unipotent progenitor cells are sometimes referred to as
stem cells
Typically stem cell generates an intermediate cell type or different cell
types prior to achieving a mature differentiated state a precursor or
progenitor cell
Mesenchymal stem cells (MSCs)

Multipotent progenitor cells which are capable of differentiating into several

connective tissue cell types osteocytes, chondrocytes, adipocytes, tenocytes
and myocytes
They can help to form trabecular bone, tendon, articular cartilage, ligaments, and
part of the bone marrow
MSCs are found post-natally in the nonhaemopoietic bone marrow stroma, which
comprises a heterogeneous population of cells including reticular cells, adipocytes,
osteogenic cells, smooth muscle cells, endothelial cells and macrophages
MSCs can also be derived from periosteum, fat and skin multipotent cells
capable of differentiating into cartilage, bone, muscle, tendon, ligament and fat
The mesengenic process. Hypothesized scheme of a multipotent MSC self-renewing and having the capacity to be induced into several
mesenchymal lineage pathways resulting in the formation of definitive tissues such as bone, cartilage, muscle, etc
Cleavage : Creating Multicellurarity

Fertilization cleavage divisions (blastula

In mammals :
1. Relatively slow process
2. Rotational cleavage
3. Asynchrony
4. Produce proteins
5. The compaction phenomenon

Internal cells embryo

External cells trophoblast

The endometrium responds
vascularity and capillary
permeability decidual
mediated by estrogens
The next phase gastrulation
The ball of cells of the blastula turns itself into a
multilayered structure and rearranges to form the 3
embryogenic tissue layers endoderm, ectoderm and
The mechanics of gastrulation in mammals are not well
Early organogenesis in vertebrae development :
neurulation and mesoderm segmentation
During gastrulation, the germ layers (ectoderm, mesoderm, and endoderm)
move to the positions the structure of the adult organism
At the same time, mesoderm
on either side of the middle
breaks up into blocks of cells
to form the somit, a series of
repeated segments along the
axis of the embryo
Conceptual insights of embryogenesis and
early organogenesis

The cells of the body are genetically alike but

phenotypically different

Each cell must act according to the same genetic

instruction, but it must interpret them with regard to time
and space
Pattern formation

Homeotic genes code for proteins called transcription

factors, which control gene expression

The order of homeotic genes on the chromosome

corresponds to their temporal and spatial expression on
the anteroposterior axis of the embryo
Cell differentiation

Differentiation leads to the production of a finite number

of discrete kinds of cells, each with its peculiar repertory of
biochemical activities and possible morphological

The achievement and persistence of the differentiation

state depends on a series of signals that ultimately control
the transcription of specific genes

Morphogenesis relies on a rather restricted number of cellular

activities and encompasses the formation of all tissues and
organs from the first embryonic tissue layers to the finished
limb, spine, or brain

The steps that tell cells who they are and what tissues they
should form take place in the control room

Morphogenesis is then what happens of the factory floor

Developmental anatomy of the nervus

The neural tube CNS

Neural crest peripheral nervous system
Lumbal and sacral nerve roots conus
medullaris cauda equina
Clinical Correlation
- Spina Bifida -
Bone as Structure & Organ

Anatomical structures
Provide rigid framework for the trunk and extremities
Locomotor function
Protect vulnerable viscera
Physiological organ
Hemopoietic tissue (RBC, granular leukocytes, platelets)
Reservoir of Ca, Phosphor, Mg, Na
Embryonic development of Bones
Mesoderm mesenchyme (a diffuse cellular tissue that
pluripotent) differentiates into many connective tissue
such as bone, cartilage, ligament, muscle, tendon, fascia.

Endochondral (primary center) replacement of
cartilage bones
Endochondral ossification (Growth in length):
Articular cartilage (only in short bones)

Epiphyseal plate cartilage

Intramembranous perichondrium becomes
Development of Bone (1)

6th month of embryonic

development resorption
central part of the long bone
results in the formation of
medullary cavity, tubulation
At the time of the birth
distal femoral epiphysis forms
the secondary center of
ossification, provides growth
in the length of the bone
Development of Bone (2)

Short bones (ex. Carpal

bones) are developed by
endochondral ossification
Skull bones & clavicle are
developed by
ossification width
Warning : thalidomide and
rubella infection affect the
bones development.
Epiphyseal Plate (1)

Epiphyseal plate cartilage, provides growth of the

metaphysis and epiphysis, maintain the balance with 2
process :
Interstitial growth of the cartilage plate make bone thicker,
moving away the epiphyseal plate from metaphysis
Calcification death and replacement of cartilage on
metaphyseal through endochondral ossification
Epiphyseal Plate (2)

Zones in epiphyseal
Resting cartilage
Young proliferative cartilage
Maturing cartilage
Calcifying cartilage
Epiphyseal Plate (3)

Hormonal control of the longitudinal bone growth: Growth

Produce insulin-like growth factor in the liver
Sex hormones post-pubertal growth spurt
Glucocorticoid inhibition of growth, ex. Cushing syndrome
As the epiphyseal plate growth farther away, metaphysis
should remodeled continuously through deposition of
osteoblast and osteoclastic resorption
Wolffs Law

Wolffs law (cortical

thickening on the concave
site) :

Positive bone balance

(child, stress) :
deposition > resorption
Negative bone balance
(elderly) :
resorption > deposition
Anatomical &Histological structures of Bone
Bone Maturity
Immature bone :
first type of bone,
never seen under normal
condition after 1 year.
Exception: fracture healing,
reaction to an infection, tumor.
Mature bone :
haversian system/osteon,
permit vascularization.
Cancellous bone has eight
times greater surface area than
cortical bone.
Blood Supply of Bone
In children, fracture heals faster than adult because the
covering periosteum is thick and loosely attached to the
cortex and it produces new bone readily.

Blood supply to the long bone:

Afferent vascular system:
Metaphyseal arteries: 2/3 inner cortex
Periosteal arteries: 1/3 outer cortex
Efferent vascular system: conveys venous blood
Intermediate vascular system: capillary within cortex

Direction of blood flow: centrifugal from medullary cavity to

Biochemistry of Bones
Biochemistry of bones:
Organic substances: 30%
Inorganic substances: 60%
Water: 10%
Organic substances:
Bone cell & matrix (collagen, noncollagen)
Inorganic substances:
phosphorus Na,
Homeostasis of Bone (1)
Enzymes : Bone alkaline phosphatase(produce matrix), produced by
Ca & Phosphorus (Hydroxyapatite crystal) metabolism: regulate by 3
hormones :
Active metabolites of vitamin D
Metabolically active tissues for those hormones :

Total Ca plasma : 9.0 10.4mg/100mL ( Ca2+ , albumin binded)

Pi plasma adult : 3mg/100mL
Pi plasma child : 5mg/100mL
Homeostasis of Bone (2)
PTH actions : Vit D metabolites actions :
secretion stimulated by increase absorption of both
hypocalcemia Ca and Pi from intestine
reabsorps bones and resorps Ca mobilize Ca from bone
from renal tubule elevate Ca plasma
inhibits Pi resorption from renal stimulated by hypoCa,
tubule HypoPi, PTH
stimulate 1,25 (OH)2D

Calcitonin actions :
Produce by thyroid gland
stimulated by hypercalcemia
inhibited by hypocalcemia
decrease bone resorption,
surpress osteoclastic activity
(th/ of Paget disease and
Joint and articular cartilage

Joint = simple junction between 2 / more bones

Classification :
Syndesmosis : bound together by fibrous tissue, e.g. skull
Synchondrosis : bound together by cartilage, e.g. epiphyseal plate
Synostosis : obliteration of joint becomes bony union. Some Syndesmosis and
synchondrosis unite became this
Symphysis : covered by hyaline cartilage & joined by fibrocartilage and strong
fibrous tissue. Ex: intervertebral. Less movement, more stability
Synovial joint : covered by hyaline cartilage, joined by fibrous tissue capsule
enclosing a joint cavity that contains synovial fluid. Free movement, less stability
Once cartilage is damaged, its ability to heal is so limited,
results inevitably in progressive degenerative arthritis
Anatomical structure: Histological structure:
The convex surface always > Has no vessels, nerve
concave, thus provide gliding Matrix consist of 70-80%
motion water, 10-15% collagen, 10-
Articular cartilage has rubber 15% proteoglycan
consistency, also called hyaline Proteoglycan glue collagen
(frosted glass). together
Lubricated by mucin Chondrocytes produce
(hyaluronate) fluid. proteoglycan and collagen,
Synovial membrane respond to active / passive
Menisci motion, substances such as
growth factor, interleukins,
and drugs.
Chondrocytes get nutrient
from synovial fluid.
Bone and cartilage, similarity and differences

Similarity : Differences :
Derived from mesenchym
Have cells embedded in
Collagen type I
lacuna and have matrix
Highly vascular
Matrix are calcified
Collagen type II
Poorly vascular
Structure and function of synovial membrane

Consist of 2 layers : outer, inner Synovial fluid :

Inner layer : produce Dyalisate of plasma
macrophages, hyaluronate Clear, yellowish, vicous fluid
Great surface area (because of Contain glycoprotein and
enormous numbers of villi) lubricant hyaluronic acid
Nourishing and lubricating
Adult : <5mL
Also contain in synovial burse
and tendon sheath
Total cell count < 200/mL,
predominantly MN
macrophages & lymphocytes
No fibrinogen thats way it
wont clot
Active movement of articulated skeleton
Maintaining posture
Basic Property
Isotonic contraction
Isometric contraction
Eccentric contraction
Type of Muscle fiber

Type I Type II
Slow twitch Fast-twitch
Slow oxidative Glycolytic
High repetition For activities that require
Low-load endurance speed and power
activities red fibre
white fibre
Prefer oxidative chain as
main energy source

Composed of dense
connective tissue
abundant in nonextensile
collagen (type I) fibres
known as fibrous connective
Remarkable tensile strength
Thank you
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