Unit IV: Connective Tissue

Question 1

Functions of connective tissue

Answer 1

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

Question 2

Core cells of the CT family

Answer 2

Mesenchymal cells 
Fibroblasts 
Myofibroblasts
Adipocytes 
Osteoblasts & osteocytes
Chondrocytes

Question 3

Mesenchymal cells

Answer 3

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

Question 4

Fibroblasts

Answer 4

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

Question 5

Connective Tissue “immigrant” cells

Answer 5

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

Question 6

Functions of Macrophages

Answer 6

1. Phagocytosis of cells and ECM - engulf invading microbes, removal of damaged tissue, remodeling of normal tissue
2. Promote/control angiogenesis
3. Secrete and respond to cellular signals
4. Remodel tissue

Question 7

Wound response (Phase I)

Answer 7

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

Question 8

Wound Response (Phase II)

Answer 8

New tissue formation; fibroblasts are stimulated to divide and secrete ECM components, epithelial stem cells divide and differentiate, and macrophages signal angiogenesis

Question 9

Wound response (Phase III)

Answer 9

Tissue remodeling; excess fibroblasts die by apoptosis, macrophages remove damaged tissue materials

Question 10

Functions of cartilage

Answer 10

1. To provide a resilient but pliable support structure

2. To direct the formation and growth of bone

Question 11

Formation & growth of cartilage

Answer 11

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”

Question 12

Perichondrium

Answer 12

Perichondrium - the connective tissue sheath that surrounds growing cartilage and supplies it with diffusing nutrients

Question 13

Hyaline Cartilage

Answer 13

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

Question 14

Types of cartilage

Answer 14

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

Question 15

Formation & growth of bone

Answer 15

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)

Question 16

Osteocytes

Answer 16

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

Question 17

Formation & Function of Osteoclasts

Answer 17

Polyploid cells (multiple nuclei) derived from the hematopoetic lineage via blood monocytes, which function to:

1. Degrade cartilage during bone growth
2. Continuously & specifically degrade bone matrix
3. Promote angiogenesis
4. Promote innervation of bone
5. 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

Question 18

Formation of bony matrix

Answer 18

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

Question 19

Intramembranous Ossification

Answer 19

The process by which flat bones form; groups of mesenchymal cells condense, transform into osteoprogenitors, and differentiate into osteoblasts which secrete osteoid

Question 20

Endochondral Ossification

Answer 20

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)

Question 21

How do bones grow?

Answer 21

1. 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
2. Bones grow in thickness by appositional growth at their surfaces

Question 22

How is bone regulated?

Answer 22

1. Short range signals - i.e. Bone Morphogenic Proteins (BMPs) produced in the local bone environment to stimulate chondrogenesis or osteogenesis
2. Long range signals - i.e. Parathyroid hormone which stimulates Ca2+ release (bone resorption) and Calcitonin which stimulates Ca2+ uptake into bone (bone formation)
3. Mechanical stress
4. Neuronal stimulation

Question 23

Osteon

Answer 23

Refers to a region of bone consisting of a Haversian canal and its surrounding lamellae

Question 24

Isogenous groups

Answer 24

Refers to groups of chondrocytes located within a lacuna; these cells are clones derived from mitosis

Question 25

Layers of blood vessels

Answer 25

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

Question 26

Elastic Arteries

Answer 26

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

Question 27

Muscular arteries

Answer 27

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

Question 28

Arterioles

Answer 28

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

Question 29

Capillary structure & types

Answer 29

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)

Question 30

Venules

Answer 30

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

Question 31

Veins

Answer 31

Consist of tunica intima, media comprised of increasing layers of smooth muscle, and progressively thickening adventitia containing vasa vasorum in large veins

Question 32

Lymph vessels

Answer 32

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