FISIOLOGI

TULANG
 Primary Functions the Skeletal System
1. Support.
• The skeletal system provides structural support for the
entire body.
• Individual bones or groups of bones provide a framework for
the attachment of soft tissues and organs.

2. Storage of Minerals and Lipids.

• Minerals are inorganic ions that contribute to the osmotic
concentration of body fluids.
• Minerals participate in various physiological processes, and
several are important as enzyme cofactors.
• Calcium is the most abundant mineral in the human body.
• The calcium salts of bone are a valuable mineral reserve that
maintains normal concentrations of calcium and phosphate
ions in body fluids.
• The bones store energy reserves as
Martini lipids in
Fundamentals areas
of Anatomy andfilled with
Physiology 9e, 2012
 Primary Functions the Skeletal System
3. Blood Cell Production.
• Red blood cells, white blood cells, and other blood elements are
produced in red bone marrow, which fills the internal cavities of
many bones.

4. Protection.
• Many soft tissues and organs are surrounded by skeletal
structures.
• The ribs protect the heart and lungs, the skull encloses the
brain, the vertebrae shield the spinal cord, and the pelvis
cradles digestive and reproductive organs.

5. Leverage.
• Many bones function as levers that can change the magnitude
and direction of the forces generated by skeletal muscles.
• The movements produced range from the precise motion of a
Martini Fundamentals of Anatomy and Physiology 9e, 2012
fingertip to changes in the position of the entire body.
 Bone Structure
• The diaphysis is connected to each epiphysis at
a narrow zone known as the metaphysis
• The wall of the diaphysis consists of a layer of
compact bone, or dense bone.
• Compact bone, which is relatively solid, forms
a sturdy protective layer that surrounds a
central space called the medullary cavity.
• The epiphyses consist largely of spongy bone,
also called cancellous or trabecular bone.
• Spongy bone consists of an open network of
struts and plates that resembles latticework
with a thin covering, or cortex, of compact bone.
This superficial layer covering spongy bone
is also known as cortical bone.

Martini Fundamentals of Anatomy and

Physiology 9e, 2012
 Bone

Compact bone
• Outer layer of bone, surrounding trabecular bone
& bone marrow cavity
• Much denser, less active metabolically
• Compose 75% of bone in the body
• Nutrients are provided via Haversian canals blood
vessels
• Collagen arrangement around Haversian canals 
osteon cylinders (Haversian system)

Trabecular bone
• Spongy bone: bone spicules separated by spaces
• Compose 25% of bone in the body
• Nutrients diffuse from bone ECF
 Bone
Organic matrix
• 30% content of compact bone
• Collagen fibers: 90-95%
 Fibers extend primarily along the lines of tensional force; give the
powerful tensile strength
• Homogeneous gelatinous medium – ground substance: 5-10%
 Extracellular fluids + proteoglycans (chondroitin sulfate & hyaluronic
acid)
 Help control the deposition of calcium salts

Bone salts
• 70% content of compact bone
• Crystalline salts (principally calcium & phosphate): hydroxyapatite, Ca/P
ratio: 1.3-2.0; long, flat shaped crystal plates; compressional strength
• Mg, Na, K, carbonate

Bone cells
• Osteoblasts, Osteocytes, Osteoclasts
 Bone cells

·Osteoblasts
 Bone forming cells
 Derived from bone marrow cell precursors
 Secrete large quantities of type I collagen + other matrix
proteins
 Secrete growth factors IGF-1, secrete cytokines IL-1, IL-6
 Receptors for PTH, DHC, estrogens
 Differentiate into osteocytes

·Osteocytes
 Rounded cells surrounded by bone matrix
 Send long processes:
 into the canaliculi, contact and form ‘tight junctions’
with processes of other osteocytes, ramify throughout
the bone
 Bone cells

·Osteoclasts
Derived from hematopoietic stem cells through monocytes

 Erode and resorb previously formed bone:

 proton pump  acidify the matrix ( pH 4) 
dissolves hiydroxyapatite  calcium and
phosphate ion
 acid proteases dissolve collagen  amino acids
 shallow depression in the bone – bone-
resorbing compartment
FIGURE 26-1  Bone cells and their interrelated activities. Hormones, cytokines, growth
factors, and signal-transducing molecules are key in their formation and maturation, and
allow communication between osteoblasts and osteoclasts. Bone resorption and formation
in remodeling are coupled processes that are controlled by systemic factors and local
cytokines, some of which are deposited in the bone matrix. BMP, bone morphogenic protein;
LRP5/6, LDL receptor related proteins 5 and 6.
 Paracrine molecular mechanisms
that regulate osteoclast formation
and function.
 Osteoclasts are derived from the
same stem cells that produce
macrophages.
 Osteoblast/stromal cell membrane-
associated RANK ligand (RANKL)
binds to its receptor RANK located
on the cell surface of osteoclast
precursors. This interaction in the
background of macrophage colony-
stimulating factor (M-CSF) causes
the precursor cells to produce
functional osteoclasts.
 Stromal cells also secrete
osteoprotegerin (OPG) which acts as
a decoy receptor for RANKL,
preventing it from binding the RANK
receptor on osteoclast precursors.
Consequently OPG prevents bone
resorption by inhibiting osteoclast
differentiation.
Figure 19-22 Role
of osteoblasts in
governing osteoclast
development and
activity.

Sherwood Human
Physiology From Cells to
Systems 9e, 2016
 Figure 19-22
Role of osteoblasts in
governing osteoclast
development and
activity.

Sherwood Human
Physiology From Cells to
Systems 9e, 2016
 Osteoblast – Osteoclast Communication

osteoblast (&
(& osteoblast
osteoblast precursors)
precursors)

estrogens
estrogens + -- glucocorticoids
glucocorticoids + -- estrogens
PTH
osteoprotegerin
osteoprotegerin (OPG)
(OPG) OPG-ligand
free-floating
free-floating decoy
decoy receptor
receptor (RANK
(RANK ligand)

osteoclast
osteoclast precursors
precursors osteoclast
osteoclast +
RANK
RANK receptor
receptor RANK
RANK receptor
receptor
+
osteoclast
osteoclast activity
activity

RANK
RANK ligand
ligand bone resorption
(osteoblast)
(osteoblast) +
PTH,
PTH, DHC
DHC (vit
(vit D
D33),
), IL
IL 1-
1- 44 -- 6-11-17,
6-11-17, TNF-alfa
TNF-alfa
 Bone Formation & Resorption

Bone
B is constantly being resorbed and formed

Modelling
o Processes involved in formation of the skeleton

o Most active during childhood and adolescence

Ceases at maturity (age 18-20 yrs)

o Long bones increase in diameter, change shape and develop a

marrow cavity related to stresses and strains imposed on skeleton
by gravity and other factors

o Bone strength adjustment to heavy loads /mechanical forces 

changes in bone shapes and thickness  bone rearrangement for
proper support
 Bone Formation & Resorption

Bone
Bone is
is constantly
constantly being
being resorbed
resorbed and
and formed
formed

Remodelling
Remodelling

 Processes
Processes occurring
occurring at
at bone
bone surfaces
surfaces before
before and
and after
after adult
adult
development
development toto maintain
maintain the
the structural
structural integrity
integrity of
of the
the bone
bone
that
that continues
continues throughout adult life

 No
No net
net gain or loss of skeletal mass after
after longitudinal growth
growth
has
has ceased.
ceased. Bone
Bone resorption
resorption equally
equally balanced
balanced byby bone
bone
formation
formation in
in a healthy
healthy skeleton
skeleton

 Local
Local process:
process: bone-remodeling
bone-remodeling units 
 osteoclasts
osteoclasts resorb
resorb
bone,
bone, osteoblasts
osteoblasts form new bone

 100
100 day
day cycle
cycle (3-4
(3-4 months;
months; 33 weeks
weeks resorption
resorption by
by
osteoclasts,
osteoclasts, deposition
deposition afterwards
afterwards by
by osteoblasts)
osteoblasts)
 Bone Formation & Resorption

Equilibrium Between Bone Deposition and Absorption

oIn growing bones, the rate of bone deposition exceeds that of
bone absorption
oThe epiphyses of long bones fuse  growth ceases  maximal
height achieved (20-21 yrs)  peak bone mass age (35 yrs): the
rate of bone deposition and bone absorption are equal /
constant total bone mass / plateau
oAfter 35 yrs: the rate of bone absorption exceeds that of bone
deposition  osteopenia  osteoporosis
o
 Bone Formation & Resorption

Repair of a fracture

 Maximal activation of all periosteal and intraosseous

osteoblasts at the fracture site

 Immediate formation of immense number of osteoblasts 

development of large bulge of new organic matrix followed
by calcium salts deposition  callus formation; then
reshaped into appropriate structure within months
Mechanisms of Bone Growth
Silverthorn Human Physiology 5th ed, 2010
 Growth In Thickness

• Growth in thickness of bone is achieved by adding new bone on top of the outer
surface of existing bone.

• This growth is produced by osteoblasts within the periosteum, a connective

tissue sheath that covers the outer bone.

• As osteoblast activity deposits new bone on the external surface, other cells
within the bone, the osteoclasts (“bone breakers”), dissolve the bony tissue on
the inner surface next to the marrow cavity.

• In this way, the marrow cavity enlarges to keep pace with the increased
circumference of the bone shaft.
Sherwood Human
Physiology From Cells to
Systems 9e, 2016
 Growth In Length

• Growth in length of long bones is accomplished by a different mechanism.

• Bones lengthen as a result of activity of the cartilage cells, or chondrocytes, in
the epiphyseal plates.
• During growth, cartilage cells on the outer edge of the plate next to the epiphysis
divide and multiply.
• As new chondrocytes are formed on the epiphyseal border, the older cartilage
cells toward the diaphyseal border are enlarging.
• This combination of proliferation of new cartilage cells and hypertrophy of
maturing chondrocytes temporarily widens the epiphyseal plate.
• This thickening of the intervening cartilaginous plate pushes the bony epiphysis
farther away from the diaphysis.
Sherwood Human
Physiology From Cells to
Systems 9e, 2016
 Growth In Length

• Soon the matrix surrounding the oldest hypertrophied cartilage becomes calcified.

• Because cartilage lacks its own capillary network, the survival of cartilage cells depends on
diffusion of nutrients and O2 through the matrix, a process prevented by the deposition of
calcium salts. As a result, the old nutrient-deprived cartilage cells on the diaphyseal border
die.

• As osteoclasts clear away dead chondrocytes and the calcified matrix that imprisoned them,
the area is invaded by osteoblasts, which swarm upward from the diaphysis, trailing their
capillary supply with them.

• These new tenants lay down bone around the persisting remnants of disintegrating
cartilage until bone entirely replaces the inner region of cartilage on the diaphyseal side of
the plate. Sherwood Human
Physiology From Cells to
Systems 9e, 2016
 Growth In Length

• When this ossification (“bone formation”) is complete, the bone on

the diaphyseal side has lengthened and the epiphyseal plate has
returned to its original thickness.

• The cartilage that bone has replaced on the diaphyseal end of the plate
is as thick as the new cartilage on the epiphyseal end of the plate.

• Thus, bone growth is made possible by the growth and death of

cartilage, which acts like a “spacer” to push the epiphysis farther out
while it provides a framework for future bone formationon the end of
the diaphysis Sherwood Human
Physiology From Cells to
Systems 9e, 2016
 Rangkuman Bone Growth

During growth

Epiphyseal plate

 Plate of actively proliferating cartilage

 Separates epiphyses of long bones from its shaft
 Lays down new bone on the end of the shaft, finely balanced cycle of cartilage
growth, matrix formation and calcification of cartilage

 Its width is proportionate to the rate of growth, affected by hormones, most

markedly by GH and IGF-1

 Linear bone growth ceases after the epiphyses unite with the shaft of the bone
(epiphysial closure):
> Cartilage cells stop proliferating, hypertrophic  vascularization, ossification.
> Epiphysial closure of bones is an orderly temporal sequence  “bone age” can be
determined by x ray
 Bone Growth
Fetal development
Enchondral bone formation
• Most of the bones
• Modeled in cartilage transformed into bone /
ossification

Intramembranous bone formation

• Clavicles, mandibles, bones of the skull
• Mesenchymal cells form bones
 Osteoporosis
• A decrease in bone density resulting from reduced deposition of the
bone’s organic matrix (see the accompanying figure),
• The condition is especially prevalent among women following menopause
(permanent cessation of menstruation), owing to the marked drop in
bone-preserving estrogen.
• 30% of postmenopausal women have osteoporosis. Following menopause,
women start losing 1% or more bone density each year.
• Skeletons of elderly women are typically only 50% to 80% as dense as at
their peak at about age 35, whereas elderly men’s skeletons retain 80% to
90% of their youthful density.
• Similar to estrogen, testosterone also helps preserve bone density, but
unlike women’s programmed withdrawal of estrogen at menopause, men
do not experience a similar built-in loss of testosterone secretion
Sherwood Human
Physiology From Cells to
Systems 9e, 2016
 Osteoporosis
• Osteoporosis is responsible for the greater incidence of bone fractures
among women older than age 50 years than among the population at large.

• One in three women with osteoporosis ends up with a fractured bone, most
commonly of the hip or spine, which may lead to permanent disability or
even death.

• Because bone mass is reduced, osteoporotic bones are more brittle and
more susceptible to fracture in response to a fall, blow, or lifting action that
normally would not strain stronger bones.

• For every 10% loss of bone mass, the risk of fracture doubles.

• Half of all American women have spinal pain and deformity by age 75.
Sherwood Human
Physiology From Cells to
Systems 9e, 2016
FIGURE 26-9  Pathophysiology of postmenopausal and senile
osteoporosis
Robbins & Cotran Pathologic Basis of Disease 8 th ed,
 Sherwood Human
Comparison of normal and osteoporotic bone. Note the reduced Physiology From
Cells to Systems
density of osteoporotic trabecular bone compared to normal
9e, 2016
trabecular bone.
FIGURE 26-10  Osteoporotic vertebral body (right) shortened by
compression fractures compared with a normal vertebral body. Note that the
osteoporotic vertebra has a characteristic loss of horizontal trabeculae and
thickened vertical trabeculae.
Robbins & Cotran Pathologic Basis of Disease 8 th ed,
2010