LECTURE 1 (Connective Tissue) Flashcards

1
Q

What are the different types of tissue?

A
  • Epithelium Tissue
  • Connective Tissue
  • Muscle Tissue
  • Nervous Tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the functions of the different types of tissues?

A

Epithelium = Lines internal and external surfaces including hollow organs & also forms glands

Connective = Provides support and fills spaces

Muscle Tissue = Produces force and movement

Nervous Tissue = Carries and integrates electrical information

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the properties of connective tissue?

A
  • Provides a matrix that SUPPORTS and CONNECTS tissues and cells
  • Interstitial fluid gives METABOLIC SUPPORT to cells as a medium for diffusion
  • ## Unlike other tissues, consists mainly of ECM (ECM consists of protein fibers like collagen & elastic fibers and ground substance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What does Ground substance consist of?

A
  • Anionic, hydrophobic proteoglycans
  • Glycosaminoglycans
  • Multiadhesive glycoproteins (laminin, fibronectin & integrins)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How does the ECM provide structural support for the cell?

A

Glycoproteins bind to other matrix components and to integrins in cell membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the role of Water in the ECM?

A

Water allows the exchange of nutrients and metabolic waste between cells and the blood supply

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What does the variety of connective tissue types reflect?

A

Structural, functional and pathologic diversity of connective tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where does all connective tissue originate from?

A

EMBRYONIC MESENCHYME which is a tissue developing mainly from the middle layer of the embryo, the MESODERM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are Mesenchymal cells?

A

Undifferentiated cells with a large and prominent euchromatic nuclei and fine chromatin. They are surrounded by an ECM that they produced and that consists largely of a simple ground substance rich in hyaluronan (hyaluronic acid) with very little collagen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What do the large and prominent nuclei in Mesenchyme cells indicate?

A

High levels of synthetic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where do Mesodermal cells migrate?

A

They migrate from their site of origin in the embryo and travel to surround and penetrate developing organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Apart from connective tissue, what does the embryonic mesenchyme include?

A

Stem cells for other tissues (e.g blood, vascular endothelium & muscle)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are properties of Fibroblasts?

A
  • Key cells in connective tissue
  • Originate from mesenchyme cells but found primarily in connective tissue
  • Function as extracellular fibers and in ground substance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the properties of Macrophages, plasma cells and mast cells?

A
  • Originate from hematopoietic stem cells in bone marrow
  • Circulate in blood and function in connective tissue
  • TRANSIENT CELLS (alongside leukocytes) where they perform functions for a SHORT PERIOD then die by APOPTOSIS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the function of Fibroblasts?

A

Fibroblasts synthesise and secrete collagen and elastin as well as GAGs, proteoglycans and multi adhesive glycoproteins that comprise the ground substance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How can you tell what you’re looking at is a Fibroblast?

A
  • Large active nuclei
  • Eosinophilic cytoplasm that tapers off in both directions along the axis of the nucleus “spindle-shaped”
  • Difficult to distinguish in H&E stained sections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do Quiescent and active fibroblasts differ?

A

ACTIVE FIBROBLAST CELLS (“fibroblast”)
- More abundant and irregularly branched cytoplasm
- More Rough endoplasmic reticulum (RER)
- Well developed Golgi apparatus
- Large, euchromatic nucleus and prominent nucleolus

QUISCENT FIBROBLAST CELLS (“fibrocyte”)
- Smaller
- Spindle-shaped with fewer processes
- Less RER
- Darker, heterochromatic nucleus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What happens when fibroblasts are stimulated by growth factors?

A

Cell cycling and mitotic activity resume when the tissue requires additional fibroblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How are fibroblasts involved in wound healing specialised for their function ?

A

They are called MYOFIBROBLASTS

Myofibroblasts have a well-developed CONTRACTILE FUNCTION and are enriched with a form of ACTIN also found in smooth muscle cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the properties of Adipocytes?

A
  • Found in connective tissue
  • Large, mesenchymally derived cells
  • Specialised for CYTOPLASMIC STORAGE OF LIPID as neutral fats or for PRODUCTION OF HEAT
  • Adipose connective tissue (large population of adipocytes) CUSHION and INSULATE the skin and other organs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the properties of Macrophages?

A
  • Abundant at sites of inflammation
  • Highly developed phagocytic activity
  • Specialise in turnover of protein fibers and removal of apoptotic cells, tissue debris and other material
  • Eccentrically (not centre) located, oval or kidney-shaped nucleus
  • Present in connective tissue of most organs
  • Well-developed Golgi complexes and many lysosomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Where are Macrophages derived from?

A

MONOCYTES

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How are Macrophages formed?

A

1) MONOCYTES cross epithelial wall of small venues to enter connective tissue where they DIFFERENTIATE, MATURE, and become MACROPHAGES
2) Monocytes formed in the YOLK SAC during EARLY EMBRYONIC DEVELOPMENT circulate and become resident in developing organs throughout the body forming the MONONUCLEAR PHAGOCYTE SYSTEM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What happens after organ damage?

A
  • Inflammation and tissue repair
  • Macrophages become activated
  • Macrophages increase in number (mainly in connective tissue) by PROLIFERATION and RECRUITING ADDITIONAL MONOCYTES formed in the bone marrow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What does the transformation from monocytes to macrophages in connective tissue involve?

A
  • Increase in cell size
  • Increased protein synthesis
  • Increase in the number of Golgi complexes and lysosomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What else do Macrophages do apart from debris removal?

A

SECRETE GROWTH FACTORS important for tissue repair and in the UPTAKE, PROCESSING and PRESENTATION of antigens for lymphocyte activation

27
Q

What are the properties of Mast cells?

A
  • Oval or irregularly shaped cells of connective tissue
  • Filled with basophilic secretory granules that often obscure the central nucleus
  • Poorly preserved by fixatives
  • Due to high content of ACIDIC RADICALS in their sulphated GAGs they display METACHROMASIA which changed some basic dyes from blue to purple or red
28
Q

What is the function of Mast cells?

A

Locally release many bioactive substances important in the LOCAL INFLAMMATORY RESPONSE, INNATE IMMUNITY and TISSUE REPAIR.

They release substances such as
- Heparin
- Histamine
- Serine Proteases
- Eosinophil and neutrophil chemotactic factors
- Cytokines
- Phospholipid precursors

29
Q

What are Plasma cells?

A

Plasma cells are lymphocyte derived, large, ovoid cells with basophilic cytoplasm. The round nuclei frequently show peripheral clumps of heterochromatin giving the structure a “clock-face” appearance

30
Q

Describe how Leukocytes travel from the blood to connective tissue

A

Derived from circulating blood cells, Leukocytes leave blood by migrating between the ENDOTHELIAL CELLS of VENULES to enter connective tissue. This increases greatly during inflammation.

31
Q

What are the characteristic events of inflammation?

A
  • Increased blood flow
  • Vascular permeability
  • Entry and migration of leukocytes
  • Activation of macrophages for phagocytosis
32
Q

What happens when inflammation begins?

A
  • Local release of chemical mediators from various cells, the ECM and blood plasma proteins
  • Mediators act on local blood vessels, mast cells, macrophages & other cells to induce events characteristic of inflammation
33
Q

What happens to leukocytes after functioning in connective tissue?

A
  • Most undergo APOPTOSIS
  • Some lymphocytes and phagocytic antigen-presenting cells leave the INTERSTITIAL FLUID of CONNECTIVE TISSUE, enter blood or lymph and move to selected LYMPHOID ORGANS
34
Q

What are the fibrous components of connective tissue?

A

Elongated structures formed from proteins that polymerise after secretion from fibroblasts

35
Q

What are the three main types of fibers?

A
  • Collagen
  • Reticular fibers
  • Elastic fibers
36
Q

What is the difference between Collagen & Reticular fibers and Elastic fibers?

A

COLLAGEN and RETRICULAR FIBERS are both formed by proteins of the COLLAGEN family

ELASTIC FIBERS are composed mainly of the protein ELASTIN

37
Q

What are the properties of Collagen?

A
  • Form various extracellular fibers, sheets and networks which are extremely STRONG and RESISTANT to normal shearing and tearing forces
  • Collagen type I, II and III have polypeptide subunits that aggregate to form LARGE FIBRILS clearly visible in the electron & light microscope
38
Q

What are the properties of Collagen?

A
  • Form various extracellular fibers, sheets and networks which are extremely STRONG and RESISTANT to normal shearing and tearing forces
  • Collagen type I, II and III have polypeptide subunits that aggregate to form LARGE FIBRILS clearly visible in the electron & light microscope
  • Collagen type IV are network/sheet-forming collagens that are major STRUCTURAL PROTEINS
39
Q

What are the properties of Collagen type I?

A
  • Most abundant & widely distributed
  • Form large, eosinophilic bundles called COLLAGEN FIBERS (tendons, organs, dermis)
  • Adjacent rodlike collagen subunits which are STAGGERED with SMALL GAPS -> characteristic feature of TRANSVERSE STRIATIONS with a REGULAR PERIODICITY
  • Form large, extremely strong collagen fibers that can be further bundled by linking COLLAGENS and PROTEOGLYCANS
40
Q

What are Linking/anchoring collagens?

A

Short collagens that link fibrillar collagens to one another and to other components of the ECM

[type VII collagen binds type IV collagen and anchors the BASAL LAMINA to underlying RETRICULAR LAMINA in BASEMENT MEMBRANES]

41
Q

Summarise Collagen synthesis

A

Occurs mainly in FIBROBLASTS but occurs in many cell types. The initial PROCOLLAGEN ALPHA CHAINS are polypeptides made in the RER and in the ER three alpha chains are SELECTED, ALIGNED and STABILISED by DISULPHIDE BONDS at their CARBOXYL TERMINALS and folded as a TRIPLE HELIX

42
Q

What is distinguishable about Type II collagen?

A
  • Present in cartilage
  • Occurs as FIBRILS but does not form fibers or bundles
43
Q

What happens when Collagen fill the ECM?

A

Bundles of collagen appear white so is spread on a slide sufficiently thin to let light pass through

44
Q

What happens for Collagen renewal to take place?

A

COLLAGEN DEGRADATION

Degradation is initiated by COLLAGENASES (members of MATRIX METALLOPROTEINASES) which clip collagen fibrils/sheets to make them susceptible to further degradation by non-specific proteases

45
Q

What are the properties of Reticular fibers?

A
  • Found in delicate connective tissue (e.g immune system)
  • Mainly type III Collagen
  • Not visible in H&E preparations
  • Stained black after impregnation with silver salts
  • High content of sugar chains -> Periodic Acid-Schiff positive
46
Q

What are the properties of Elastic Fibers?

A
  • Rubberlike which allow tissues to be STRETCHED, DISTENDED and RETURNED to the original shape
  • Not strongly acidophilic
  • Stain poorly with H&E
  • Stained more darkly than collagen with other stains
  • Elastic fibers are fibrillin -> microfibrils -> cross-linked elastin
  • Secreted from FIBROBLASTS
47
Q

Describe the formation of Elastin

A

1) MICROFIBRILS form FIBRILLIN and various GLYCOPROTEINS
2) Microfibrils act as SCAFFOLDING upon which elastin is deposited
3) Elastin accumulates around the microfibrils (eventually making up most of the elastic fiber) and is responsible for the rubberlike property

48
Q

Which disease results from mutations in the fibrillin genes?

A

MARFAN SYNDROME

A disease characterised by a lack of resistance in tissues rich in elastic fibers. Since the walls in large arteries are rich in elastic component and the BLOOD PRESSURE is high in the AORTA, patients experience ANEURYSMS (aortic swelling)

49
Q

What is the Ground substance of the ECM?

A

A highly hydrated, transparent, complex mixture of Glycosaminoglycans (GAGs), Proteoglycans and Multiadhesive glycoproteins

50
Q

What are the functions of the Ground substance?

A
  • Fills the space between cells and fibers in connective tissue
  • Allows diffusion of small molecules
  • Vicious -> acts as a LUBRICANT and a BARRIER to the penetration of invaders
  • Influence various cellular activities
51
Q

What are Glycosaminoglycans/Mucopolysaccharides?

A

Long polymers of repeating disaccharide units (usually a hexosamine and uronic acid)

52
Q

What is distinguishable about Hayaluronan?

A
  • Largest GAG
  • Long polymer of GLUCOSAMINE-GLUCURONATE
  • Synthesised directly into the ECM by HYALURONAN SYNTHASE located in the cell membrane of many cells
  • Forms a VISCIOUS, PERICELLULAR NETWORK that binds to a lot of water -> allows MOLECULAR DIFFUSION through connective tissue and in LUBRICATING various organs and joint
53
Q

What are the properties of regular GAGs?

A
  • Sulfated
  • Bound to proteins
  • Synthesised in the Golgi apparatus
  • HIGH -VE CHARGE -> extended conformation -> sequester cations as well as water
  • Space-filling, cushioning and lubricant functions
54
Q

What are the properties of Proteoglycans?

A
  • Core protein covalently attached to various sulphated GAGs
  • Synthesised on RER, mature in Golgi apparatus (where GAGs are added) and secreted from cells by exocytosis
  • After secretion, bind to hyaluronan by link proteins
55
Q

What is the link between Embryonic Mesenchyme and tissue growth?

A

Embryonic mesenchyme is rich in hyaluronan and water -> wide spacing of cells and a matrix ideal for CELL MIGRATIONS and growth -> core proteins and GAGs of proteoglycans bind and hide various growth factors -> degradation of these proteoglycans release stored growth factors which help stimulate new cell growth and ECM synthesis

56
Q

What is distinguishable about Multiadhesive glycoproteins?

A

They all have multiple binding sites for cell surface integrins and for other matrix macromolecules

57
Q

What are the properties of Integrins?

A
  • Integral membrane proteins that act as matrix receptors for specific sequences on laminin, fibronectin, collagens and other ECM proteins
  • Heterodimers with two transmembrane polypeptides - alpha and beta chains
  • Great diversity of integrin alpha and beta chains -> allows different specific ECM ligands
58
Q

What is the water in the ground substance of connective tissue also called?

A

Interstitial fluid

59
Q

What is the function of Capillaries in connective tissue?

A

Bring nutrients required by cells and carry away their metabolic waste to the detoxifying and excretory organs (liver & kidneys)

60
Q

Describe how the forced act on the water in capillaries

A

HYDROSTATIC PRESSURE of blood caused by pumping action of the heart forces water OUT across capillary wall. COLLOID OSMOTIC PRESSURE produced by plasma proteins draws water back IN.

61
Q

What is the effect of the ions and low-molecular compounds having similar concentrations inside and outside the blood vessels?

A

The osmotic pressures they exert are approximately EQUAL on either side of the capillaries so cancel each other

62
Q

What happens to the excess water that is pushed out the capillaries?

A

They DO NOT accumulate in connective tissue but drain continuously into LYMPHATIC CAPILLARIES that return it to the blood

63
Q

What is Edema?

A

Excessive accumulation of interstitial fluid in connective tissue

[Water comes from the blood, passing through the capillary walls that become more permeable during inflammation and produces slight swelling]