Connective Tissue I

Question 1

Where are connective tissues found?

Answer 1

They are found beneath the basal lamina of epithelial tissue as well as around all other types of tissues like nerves, muscle, blood vessels etc. All tissues are separated from it by basal lamina.

Question 2

What does connective tissue do?

Answer 2

Forms a conduit for and regulates the movements of metabolites, O2. It provides a medium through which cells reside and move, and regulates the movement and phenotypes of the cells that live in it.

Question 3

What is the composition of connective tissue?

Answer 3

Cell and extra cellular matrix. The ECM is composed of proteins and other molecules. The composition of the ECM determines the properties of the connective tissue in that area.

Question 4

What are the two major cell types in connective tissue?

Answer 4

The connective tissue cell family and the connective tissue immigrants.

Question 5

What are the cells of the connective tissue cell family?

Answer 5

They are the cells that actually make the connective tissue itself. All are derived initially from mesenchymal stem cells. The central cell of most connective tissue is the fibroblast, which are fully differentiated and capable of producing the components of the ECM. Fibroblasts are unique in that they can also divide and transform into other cells of the CT family like osteoproginators, adipocytes, smooth muscle, and chondrocytes (cartilage producers).

Question 6

If mesenchymal stem cells persist throughout life, how can the be distinguished from fibroblasts?

Answer 6

Immunohistochemistry or immunofluorescence staining MAY differentiate the cells. Basic staining will not show a difference between the two cell types.

Question 7

Where to connective tissue immigrants come from and what are they?

Answer 7

CT immigrant cells are born in the hematopoietic tissue in the bone marrow by hematopoietic stem cells. These are white blood cells that live in the connective tissue and perform their tasks there.

Question 8

What is unique about the function of white blood cells in the connective tissue?

Answer 8

They are activated in the CT and perform most of their functions there. The use the blood mostly as a transport medium.

Question 9

What are the five WBC types?

Answer 9

Lymphocytes, nutrophils, eosinophils, basophils (mast cells in CT), monocytes (macrophages in CT)

Question 10

In what two immune processes do CT compartments play a role?

Answer 10

Inflammation initiation and execution as well as immune defense.

Question 11

What roles do macrophages play in the ECM?

Answer 11

They phagocytose other cells and the ECM itself. They promote and control angiogenesis and are involved in tissue remodeling/repair. They are also involved in cellular communication and send signals to other cells.

Question 12

Three basic types of collagens.

Answer 12

Fibrilar collagens form long structural cables in CT (Collagen Type I is common). Fibril associated collagens, encoded by different collagen genes, form small connections between fibrilar collagen structures. Network forming collagens form thin sheets and are one of the core elements of basal lamina (Collagen Type IV is common).

Question 13

What cells produce collagen for the ECM?

Answer 13

Fibroblasts produce it in most CT. Osteoblasts produce it in bone, and chondrocytes (chondroblasts) produce it in cartilage.

Question 14

Where does translation of the collagen protein occur within the cell, what is their initial structure, and where are they modified before excretion?

Answer 14

Collagens are secreted proteins, so they are translated into the ER. Collagens are homotrimers, forming triple helices. The golgi apparatus conducts many modifications including lysine and proline hydroxylation before excreting the collagen.

Question 15

What are N-telopeptides?

Answer 15

N-telopeptides are the waste products produced when the N terminus of the collagen fibers are cleaved by proteases in the ECM. They are detectible in blood and urine and high levels of N-telopeptides are indicative of excessive bone turnover.

Question 16

What does proteolytic cleavage of the fibrillar collagen fiber in the ECM enable?

Answer 16

It triggers the capacity of the collagen fibers to link end to end. Covalent bonding between parallel fibers is achieved through another enzyme and allows the thickening of fibers. All of this must occur extracellularly, or else the fibers would coagulate inside the cell.

Question 17

How does vitamin C factor into collagen structure?

Answer 17

Vitamin C is a cofactor for enzymes involved in hydroxylation. Vit C deficiency is scurvy, which is defects in collagen formation.

Question 18

Ehlers-Danos Syndrome

Answer 18

One of many diseases of collagen formation pathway. A complex syndrome with a variety of clinical presentations that result from defects in nearly every step of the collagen production pathway. Gene mutations, hydroxylase mutations, peptidase mutations, and likely others. Disease results in easy bruising, skin disruption, joint pain and over-flexibility, and others.

Question 19

What are elastin fibers?

Answer 19

Elastins are another highly important class of fibrous proteins which are not in the collagen family. They have the property of elastic bands, and can be found in the aorta providing its stretching ability.

Question 20

How is Marfan syndrome related to CT fibers?

Answer 20

Defects in fibrillin, another connective tissue fiber, are the main source of Marfan syndrome and can cause ruptures in the aorta.

Question 21

What is the “ground substance”?

Answer 21

The substance in which the fibers of CT are enmeshed. It is composed of many types of secreted molecules including proteoglycans. Proteoglycans are peptide molecules that have very large carbohydrate structures called Glycosaminoglycans (GAGs) attached to them. GAGs are carbohydrate rich, organic, multi chain molecules. Hyaluronic acid is a secreted GAG without a protein core.

Question 22

What is the electrochemical nature of GAGs and what does this do?

Answer 22

GAGs are negatively charged and attract lots of ions and water, providing hydration. They stick together in the ECM, forming a hydrated gel-like structure through which other cells can migrate. They also bind growth factors that are stem cell regulators which may become activated at other times.

Question 23

What other molecules are secreted into the ECM?

Answer 23

Proteases, other enzymes, growth factors and signaling components, even small RNAs. The ECM is critical to regulation.

Question 24

What is the first phase of the process by which CT functions in would healing?

Answer 24

Inflammation and blood clotting are early responses. Immigrant cells become activated, mast cells are generated secreting histamines and cytokines. Macrophages and lymphocytes also secrete signaling molecules including cytokines. These cytokines (interleukins are a subset) act on blood vessels to increase their permeability and attract more immune cells to resist invading microorganisms.

Question 25

What is the second phase of the process by which CT functions in would healing?

Answer 25

Proliferation. Proliferation means an increase in fibroblast number, and dramatic increase in secretory capacity of fibroblasts. Macrophage migration continues, which increases blood vessel formation.

Question 26

What causes scarring in larger wounds?

Answer 26

If the damage is severe and the basal lamina is greatly disrupted, its developmental information is lost. Fibroblasts will automatically start producing material that will lead to scar formation. Stitching wounds together pulls the epithelial layers close so that the stem cell information and basal lamina information can be closely tied to close the breach and recapitulate the skin morphogenesis.

Question 27

What is the third phase of the process by which CT functions in wound healing?

Answer 27

Remodeling. The phase in which macrophages remove dead debris and cell replace and turn over trying to recapitulate the original structure of the damaged environment.