Lecture 1
Study of the human body from molecules and cells to tissues, organs and systems
Homeostasis
• Homeostasis is the regulation of the internal environment of a body. The body operates
within a healthy range. – so that all the cells are able to function and adjust to changes in
the following:
o factors that affect cells (osmolarity, temperature and pH)
o requirements for cells (nutrients, water, oxygen, sodium, calcium and other
inorganic ions)
o signals for communication between cells (hormones, cytokines and other chemicals
cells use to communicate)
• The endocrine system plays an important role in homeostasis because hormones modulate
the activity of cells
• Remember the endocrine system releases hormones in blood. They are ductless organs
The exocrine system releases enzymes in organs through ducts.
• Negative feedback occurs when the response to a stimulus reduces the original stimulus
(Decreases further release of the original hormone. ENOUGH IS ENOUGH)
• Positive feedback occurs when the response to a stimulus increases the original stimulus
(Increases further release of the original hormone.)
Definitions:
• Autocrine Factors → ITSELF
o Secreted or cell surface bound growth factors and cytokines that are expressed by a
cell to act on itself or adjacent cells of the same lineage.
• Paracrine factors → OTHERS LOCALLY
o Secreted or cell surface bound growth factors and cytokines that are expressed by a
cell to act locally within a tissue, frequently affecting only adjacent or nearby cells
• Endocrine factors → DISTANT OTHERS
o Secreted hormones produced in an endocrine organ to have effects on distant
organs
o Effect all target tissues in the body at once.
o Often feedback systems for regulation
o Examples : FSH, estrogen, growth hormone, insulin, PTH, Vitamin D
Role of Autocrine and Paracrine Factors
• Regulate migration, proliferation, differentiation, activity and apoptosis of cells within a
tissue. For example:
o Establish spatial relationships between cells and thus build structure within an organ
o Regulate of cell migration from vasculature as in recruitment of inflammatory cells
o Orchestrate response to hormonal stimuli
o Regulate differentiation of functional cells from stem cells
o Mediate communication between different cell types to enable coordinated
responses
,Autocrine and Paracrine Factor Signalling
• Cytokines and Growth Factors exert their effect on target cells like hormones
• They are in the extracellular space
• Receptor ligand complex activates pathways in the cell that change cell activity and gene
expression.
Paracrine Signalling is for Local Cell Regulation
• Paracrine signals are produced within a tissue to act locally
• Has inhibitory and stimulatory feedback
• Signals for :
o Clot formation → don’t want to bleed out
o Vessel repair
o Macrophage invasion
o Activation of skin repair
Bone
• All bones have thick hard and dense supporting external layer
• However inside that you have the trabecular bone. This is the spongy bone, give tensile
properties. We can jump and not break our legs
• In the Diaphysis- bone marrow is formed
• Metaphysis- is the part of the bone that grows
• Epiphysis- is the end of the long bone
Bone Matrix Composition
• Collagen: gives bone its tensile strength. INORGANIC COMPOUND→ HYDROXYAPATITE
(CACLICUM PHOSPHATE CRYSTALS)
o Type 1
o Lamellar vs woven bone
• Non-collagenous proteins: Ostoeids→ Flexibility
o Alkaline phosphatase
o Proteoglycans
, o Growth factors in bone matrix
• Bone mineral:
o Calcium & phosphate crystals as hydroxyapatite. This give the bone compressive
strength
Inside the bone there is the blood vessel
Bone as a repository for Ca2+
• Calcium is maintained within a very tight range in the plasma: 1.1-1.3mM free Ca2+
• Ca2+ has several physiological functions:
o Signalling molecule within cells, eg exocytosis of secretory vesicles and muscle
contraction
o Aids in holding cells together at tight junctions
o Co-factor in coagulation
o Affects the excitability of neurons by changing sodium permeability at the
membrane
• Bone is controlled by hormones which ultimately control the amount of free calcium
Bone Development & growth
Osteocytes are recruited form peripheral blood monocytes
Osteocytes→ Osteoclasts→ Osteoblasts
Bone resorption by osteoclasts
, Bone Formation
• Osteoblasts: bone forming cells
plump
line bone surfaces
active synthesis of matrix involvement in mineralisation
• Lining cells: flattened osteoblasts lining bone surface
• Osteocytes: osteoblasts embedded in bone matrix
connected by canaliculae involved in sensing mechanical forces
Bone formation by osteoblasts
How do these cells know what to do?
All the formation is induced by autocrine, paracrine and endocrine signals