Unit IV: Connective Tissue Flashcards
Functions of connective tissue
Provide mechanical strength & support for specialized tissues of organs
Conduct & control exchange of nutrients & signaling ligands between cell types of organs
Control behavior & function of cells that contact the ECM including: control of epithelial polarization, guidance of cell migration through ECM, control of cell proliferation & differentiation, defense against infectious agents, control of inflammation and repair due to injury
Core cells of the CT family
Mesenchymal cells Fibroblasts Myofibroblasts Adipocytes Osteoblasts & osteocytes Chondrocytes
Mesenchymal cells
Stem cell precursors to all of the connective tissue family members including osteoprogenitors, fibroblasts, and chondrocytes; primarily function in embryogenesis but small numbers persist into adulthood
Fibroblasts
Secretory engine of connective tissue, can differentiate into diverse cell types, including adipocytes; fibroblast activity is tightly regulated between active (secretory) and resting (G0) states
Connective Tissue “immigrant” cells
White blood cells that are formed in the bone marrow and migrate through the blood to enter the CT:
Lymphocytes Neutrophils, Eosinophils Mast cells (from basophils) Macrophages (from monocytes) Osteoclasts
Functions of Macrophages
- Phagocytosis of cells and ECM - engulf invading microbes, removal of damaged tissue, remodeling of normal tissue
- Promote/control angiogenesis
- Secrete and respond to cellular signals
- Remodel tissue
Wound response (Phase I)
Inflammation and blood clotting; tissue damage releases platelets into the CT, activating a downstream cascade of events including:
Mast cells secrete histamine
Cytokines (i.e. interleukins) cause an increase in capillary permeability to water and cells, promoting migration of immune cells to the damaged tissue
Wound Response (Phase II)
New tissue formation; fibroblasts are stimulated to divide and secrete ECM components, epithelial stem cells divide and differentiate, and macrophages signal angiogenesis
Wound response (Phase III)
Tissue remodeling; excess fibroblasts die by apoptosis, macrophages remove damaged tissue materials
Functions of cartilage
- To provide a resilient but pliable support structure
2. To direct the formation and growth of bone
Formation & growth of cartilage
Mesenchymal cells in connective tissue are stimulated to differentiate into chondrocytes, which secrete ECM and become embedded in lacuna; within the lacuna, chondrocytes divide to form chains of clones which become isolated within their own lacunae, leading to interstitial growth (growth from within)
Cartilage also undergoes appositional growth, “growth from the surface”
Perichondrium
Perichondrium - the connective tissue sheath that surrounds growing cartilage and supplies it with diffusing nutrients
Hyaline Cartilage
Forms the cartilaginous model of the fetal skeleton as well as much of the articular cartilage of joints; ECM is rich in proteoglycans (especially hyaluronic acid) and highly hydrated
Types of cartilage
Hyaline Cartilage - common in joint articulations
Elastic Cartilage - located in the outer ear, epiglottis, etc.
Fibrocartilage - typically found at the junction between bone and tendon
Formation & growth of bone
Mesnechymal stem cells differentiate to give rise to osteoprogenitor cells (bone stem cells), which are restricted to the bone lineage and differentiate into osteoblasts, which are the main secretory cell of bone
Osteoblasts secrete and eventually become encased within bone matrix; within the bony matrix, osteoblasts differentiate into osteocytes, which do not divide or produce matrix
Therefore, bones undergo appositional growth only (no interstitial growth)
Osteocytes
Quiescent cells of the bone matrix that do not divide or secrete materials, but send out processes (canaliculi) that form gap junctions with neighboring osteocytes allowing for direct cell-cell communication
Formation & Function of Osteoclasts
Polyploid cells (multiple nuclei) derived from the hematopoetic lineage via blood monocytes, which function to:
- Degrade cartilage during bone growth
- Continuously & specifically degrade bone matrix
- Promote angiogenesis
- Promote innervation of bone
- Mobilize Calcium - osteoclasts secrete enzymes that liberate calcium from the bony matrix; calcium is endocytosed by the osteoclast and released into the blood by transcytosis
Formation of bony matrix
Osteoblasts initially secrete a soft mixture of proteins and GAGs called osteoid; next, osteoblasts secrete matrix vesicles loaded with calcium and phosphate, which crystallize in the osteoid to form hydroxyapetite (CaPO4), which forms the mineralized substance of bones
Intramembranous Ossification
The process by which flat bones form; groups of mesenchymal cells condense, transform into osteoprogenitors, and differentiate into osteoblasts which secrete osteoid
Endochondral Ossification
The process by which cartilaginous models of long bones are replaced by bony matrix; perichondrium surrounding the cartilaginous model contains mesenchyme cells, which become re-directed to produce osteoprogenitor cells; osteoclasts burrow into the cartilaginous model and stimulate the in-growth of blood vessels, nerves, and osteoblast cells which begin to lay down new bony matrix in the spaces left by osteoclast activity
This process occurs in the center of the diaphysis (the primary ossification center)
How do bones grow?
- Long bones grow by interstitial division of hyaline cartilage within epiphyseal plates; osteoclasts follow the growth of cartilage from within epiphyseal plates to replace cartilage with bony matrix
- Bones grow in thickness by appositional growth at their surfaces
How is bone regulated?
- Short range signals - i.e. Bone Morphogenic Proteins (BMPs) produced in the local bone environment to stimulate chondrogenesis or osteogenesis
- Long range signals - i.e. Parathyroid hormone which stimulates Ca2+ release (bone resorption) and Calcitonin which stimulates Ca2+ uptake into bone (bone formation)
- Mechanical stress
- Neuronal stimulation
Osteon
Refers to a region of bone consisting of a Haversian canal and its surrounding lamellae
Isogenous groups
Refers to groups of chondrocytes located within a lacuna; these cells are clones derived from mitosis
Layers of blood vessels
Tunica intima - a layer of endothelial cells in intimate contact with blood
Tunica Media - Comprised of multiple layers of elastic tissue, smooth muscle, and/or collagen
Tunica Adventitia - Comprised of collagenous tissue; in larger arteries, may also contain associated vessels (vasa vasorum) that supply oxygen and nutrients to the adventitia & media
Elastic Arteries
Aorta & the larger arteries branching from it; intima contains an extra layer of collagen/elastin-rich fibers as well as fibroblasts & myointimal cells; media contains multiple elastic layers with some collagenous fibers and smooth muscle cells sandwiched in between; adventitia contains vasa vasorum
Muscular arteries
Characterized by two, well-defined elastic layers: the inner elastic lamina, between the intima and the media, and the outer elastic lamina, between the media and adventitia
Smaller muscular arteries lose the outer elastic lamina but retain the inner elastic lamina
Arterioles
Contain an inner lining of endothelial cells backed by a thin basal lamina, surrounded by 1-2 layers of smooth muscle cells and an outer layer of collagenous tissue; arterioles are the gatekeepers to local capillary beds and can greatly restrict the flow of blood
Capillary structure & types
Comprised of 1-2 layers of endothelial cells surrounded by pericytes, which are unspecialized “smooth muscle-like” cells; these are surrounded by collagenous fibrils that connect the capillary to adjacent connective tissue
Capillaries may be continuous or fenestrated, with pores in the endothelial cells that allow for bulk flow of plasma past the endothelial boundary (i.e. in the glomerulus)
Venules
Similar in structure to capillaries but endothelium is more sensitive to vasoregulatory substances that control permeability; larger, muscular venules have 1-2 layers of smooth muscle with their media and thin layers of adventitia
Veins
Consist of tunica intima, media comprised of increasing layers of smooth muscle, and progressively thickening adventitia containing vasa vasorum in large veins
Lymph vessels
Begin as small spaces in connective tissues which connect to larger spaces lined by a thin layer of squamous endothelium; as they increase in size, a thin endothelial layer surrounded by loose connective tissue is discernible, with flap-like valves
