Connective Tissue Proper and Cartilage Flashcards
What is the most common principle long-term resident cell of connective tissue?
Fibroblast
What are examples of multiadhesive glycoproteins in the ground substance?
laminin, fibronectin. They are secreted by both epithelial and principal CT cells
What combines to form proteoglycan aggregates?
proteoglycans, which are linear proteins with GAG side chains, giving a bottle-brush appearance. These are linked to a central hyaluronic acid GAG chain via linker proteins
What GAG forms the central GAG of proteoglycan aggregates and why?
Hyaluronic acid - it is longer and more rigid, tends to increase the viscosity of the ground substance. It is a long-chain linear polysaccharide
How do GAGs generally stain, and why?
Basophilic. There are often sulfate residues in GAGs such as chondroitin sulfate and keratan sulfate, which creates a negative charge. This also attracts sodium and ultimately water to the ECM
What are the three major types of fibers found in connective tissues?
Type I collagen, elastic fibers, and reticular fibers (Type III collagen)
What is the primary function of loose connective tissue?
Serves as an anchor for epithelium and area for many cells and monitoring antigen invasion of the epithelium
What is the function of fibroblasts and how are they seen by microscopy?
principle CT cell. They produce an abundant matrix of Type I collagen and elastic fibers. Can be seen by LM as an elongated nucleus and thin or often invisible cytoplasm. Have a variable morphology on TEM and can be seen surrounded by collagen fibrils with a prominent rough ER.
what are fibroblasts derived from?
Mesenchymal cells
What is the function of macrophages and where do they come from?
They are differentiated from monocytes. They are the resident phagocytic cells that ate bacteria or dying cells
How do macrophages appear by microscopy?
By LM, it is difficult to tell unless they have phagocytized something. By TEM, they contain many lysosomes and may have extending pseudopodia for phagocytosis
Where do plasma cells come from and what is their function?
Differentiate from B lymphocytes that circulate the blood. They specialize in secreting a specific immunoglobulin
How do plasma cells look by microscopy?
By LM, they have a basophilic cytoplasm because of the high concentration of rER for antibody production. By both LM and TEM, they can be identified by their “clockface” or “wagon wheel” appearance based on their nuclear marginal heterochromatin
What are the characteristics of an adipocyte?
Large cell that contains a singular triglyceride (fat) inclusion with a thin rim of cytoplasm and glycogen. Nucleus is generally pushed to the side. It is surrounded by an EXTERNAL LAMINA
What are the three functions of adipocytes?
- Energy storage -> triglycerides
- Weight control -> leptin secretion
- Hormonal modification -> secretion of estrogen from precursors
How does an adipocyte look by LM?
They have a washed out appearance. Since the lipid inclusion often washes out, appear to be a singlet ring with eccentrically flattened nucleus
What is the function of mast cells?
They promote inflammation in the presence of specific antigens binding IgE on the surface. They release granules containing heparin, histamine, and tryptase in a calcium-dependent fashion. Heparin prevents clotting and histamines promote inflammatory response.
What are the two distinctive substances produced by mast cells?
- Tryptase - a marker secreted in granules, actually cleaves the influenza virus hemagglutinin
- Leukotrienes - synthesized by plasma membrane after activation, a powerful inflammatory
How can mast cells be identified by LM?
ovoid nucleus with cytoplasm containing basophilic or metachromatic granules (stain different color than die). Granules are often lost in H&E however, because they’re water soluble. they are electron-dense granules by TEM
What can skin mast cell activation cause?
urticaria (hives)
Why is loose connective tissue good to be loose?
Leukocytes (WBCs) and other cells can easily migrate through the matrix from the blood to promote immune response to antigens, parasites, and bacteria that might breach the epithelium
What is the most abundant type of collagen in humans and what are its properties?
Type I collagen. Has high tensile strength but is very flexible
how is procollagen synthesized?
fibroblasts make pre-procollagen, rich in lysine and proline. Hydroxylation of lysine and proline is done by hydroxylases using vitamin C, all in the rough ER. Three of these fibers come together to make procollagen.
how is tropocollagen synthesized?
procollagen is packaged in Golgi and released by constitutive exocytosis. Peptidases associated with the plasma membrane of fibroblasts cleave the ends of procollagen.
How is a collagen fiber completed?
Tropocollagen self-staggers into collagen fibrils of varying diameter depending on the tissue. Fibrils assemble into larger eosinophilic fibers (aggregates) visible in the LM
How can a collagen type I fibril be recognized by TEM?
They have a banded appearance due to tropocollagen, and often appear in bunches because they assemble to fibers.
How can a collagen type I fiber be seen by LM?
They stain red or pink with H&E and have an irregular, unbranched, wavy appearance. With trichrome stains, collagenous fibers always stain BLUE. Useful for distinguishing between collagen and muscle cells
What proteins compose elastic fibers?
Elastin molecules are crosslinked by desmosine and isodesmosine, and the bunches of elastin fibers are kept organized by fibrillin (microfibril)
What stains are used to visualize elastic fibers?
Orcein, resorcin fucshin, aldehyde fucshin, and Verhoeff’s
Not easy to see without these stains because they stain only slightly eosinophilic
What is the function of dense connective tissue?
Contains mostly Type 1 collagen (some elastic) and few cells (mostly fibroblasts). Mechanically links other tissues (tendons, ligaments), or protects / supports other tissues (organ capsule)
how can dense connective tissue be told apart from muscle or peripheral nerve?
If not fixed under tension, they look similar. However, there are much fewer nuclei as collagen fibers staining deeply pink are extracellular. Type 1 collagen tends to all run in the same direction for the most tensile strength
How does dense irregular connective tissue differ and why?
Irregular dense has each subsequent layer running in a slightly oblique direction to resist stress from any direction
What is the function and general makeup of reticular connective tissue?
Made up of reticular fibers (type 3 collagen), provides support around walls of blood vessels, fat cells, nerve fibers, and muscle cells. A delicate meshwork to allow passage of cells and fluid within an organ. There is minimal ground substance
What is the primary structural difference between Type 1 and Type 3 collagen?
Type 1 collagen is wavy and unbranched, whereas Type 3 is branched perfectly like a mesh bag.
What cells produce the reticular connective tissue?
Primarily reticular cells in lymphatic tissues (a fibroblast-like cell), fibroblasts, Schwann cells (nerves), adipocytes, and muscle cells
What forms the stroma (matrix) of the bone marrow, liver, and lymphatic organs (but not the thymus)?
Reticular connective tissue (Type 3 collagen)
How do reticular cells create reticular fibers?
They create Type 3 collagen by the same mechanism fibroblasts create Type 1 collagen. The fibers of Type 3 collagen simply form that branched pattern.
What do Type 3 collagen fibers look like by TEM?
The same as type 1, very hard to distinguish.
How can you recognize reticular fibers by LM?
Type 3 collagen is very argyrophilic (stains well with silver), and is also stained by PAS (stains carbohydrates and collagen is a glycoprotein)
What causes Ehlers-Danlos Type 4?
It is a Type 3 collagen disorder than often leads to rupturing of intestines or aorta since the walls of these structures are reinforced with Type 3 collagen
What are the properties of Elastic connective tissue?
Made up mostly of elastic fibers and principally fibroblasts or smooth muscle cells. Minimal ground substance. Provides stretch and elasticity.
How are elastic connective tissue fibers organized?
Loose branching fibers, or as fenestrated (perforated) laminae or lamellae. Forms elastic laminae (one or more distinct layers) around arteries and large veins
Where can elastic connective tissue be found?
Mixed with loose and dense irregular connective tissue in the skin, as well as walls of arteries and veins
What causes Marfan’s syndrome?
mutation in microfibrillar component of elastic fibers (fibrillin). Can lead to aortic rupture.
What defines adipose connective tissue (white fat)?
Presence of unilocular adipocytes, and many blood vessels to take triglycerides in and out.
What pathway is thought to be involved with obesity in humans?
Leptin-hypothalamus pathway, regulated by adipose connective tissue.
What makes up the extracellular matrix of adipose connective tissue?
reticular fibers (Type 3 collagen) and some type 1, but the ground substance is minimal.
What are the properties and function of mesenchyme connective tissue?
Loose, primitive connective tissue found in the embyro. provides delicate meshwork for passage of cells and fluid within the organ
What are the principle cells and ECm of mesenchymal connective tissue made of?
Mesenchymal cells, which are stellate or spindle-shaped precursors of many connective tissue cells like fibroblasts, bone and blood vessels. ECM is made of Type 3 collagen and abundant ground substance favoring exchange of cells and metabolites with blood vessels for development
What cell type produces Wharton’s jelly and where is it found?
Mesenchymal cells produce it. It is non-compressible connective tissue used in the umbilical cord
What makes up the extracellular matrix of Wharton’s jelly?
Fine fibrillary component (Type 3 and some type 1 collagen). Ground substance is jelly-like and rich in hyaluronic acid (rigid) with a high concentration of sulfated GAGs. Sulfated GAGs draw Na+ which draws water to resist compression
What are the principle cells of brown fat? What is its function?
Multilocular (as opposed to unilocular) adipocytes. There are many fat inclusions and many mitochondria, which make the fat appear brown. Also filled with capillaries. It is an infantile tissue type to protect the newborn against cold -> uncoupling mitochondria to produce thermal energy
What makes up the extracellular matrix of brown fat?
Type 3 collagen fibers. the ground substance is minimal
What defines cartilage?
Flexible tissue that resists compression and provides an organizing framework for other tissues. It is AVASCULAR and ANEURAL, unless these run through on the way to somewhere else
What does hyaline refer to?
The translucent, glassy appearance of something. Especially hyaline cartilage
Where is hyaline cartilage found?
Conducting portions of respiratory pathway, and articular surfaces of bones
What are the primary cells of hyaline cartilage and what do they arise from?
Chondrocytes, which arise from chondroblasts
Where is Type II collagen primary used, and how does it differ majorly from Types I and III?
It is the fibrous component of the extracellular matrix of hyaline cartilage. However, it does not form fibers, just remains as fibrils. Fibrils have the same TEM appearance as Type 1 (and 3)
What is the primary component of hyaline cartilage ground substance?
Aggrecan. It contains high amounts of sulfated GAGs which attracts water and makes it relatively incompressible.
How does hyaline cartilage stain and why?
Very basophilic, because of the negative charges from sulfated GAGs in aggrecan. May even produce metachromatic staining
What are the two layers of the perichondrium?
peri (around), chondrium (cartilage)
- Outer layer contains fibroblasts blending with surrounding connective tissue
- Inner layer contains chondrogenic cells which can differentiate into chondroblasts (happens less in adults)
Around what hyaline cartilage would you not find perichondrium?
Articular cartilages. Explains why joints wear down and osteoarthritis results
What are lacunae?
Spaces where chondrocytes lie within hyaline cartilage.
What are the territorial matrix and interterritorial matrix
Territorial matrix - diffusion of Type 2 collagen and aggrecan from chondrocytes. Stains very blue.
Interterritorial matrix - between these territorial matrices, stains less blue (but still blue because of aggrecan’s sulfated GAGs)
What is appositional growth?
Growth from the outside, as in cartilage growth from the perichondrium
What is interstitial growth?
Growth from the inside. When mitosis of chondrocytes occurs they can create isogenic clusters inside lacunae
Where is elastic cartilage primarily found?
Epiglottis and external ear, auditory canal, and auditory tubes
Elastic cartilage has a perichondrium. How does it differ from hyaline cartilage?
- Chondrocytes are packed much more closely together.
- In addition to type 2 collagen, it is also filled with elastic fibers (produced by chondrocytes) which make it stain with the elastic stains.
Where is fibrocartilage found?
Pubic symphysis, spinal discs, meniscus of knee, temporomandibular and sternoclavicular joints
What is distinctive about fibrocartilage?
- It lacks a perichondrium
- The fibrous component contains large Type 1 collagen fibers (produced by fibroblasts, not the chondrocytes), responsible for eosinophilia in tandem with basophilia created by aggrecan
How does fibrocartilage serve as a strong anchor for bone?
It’s type 1 collagen fibers are continuous with the dense regular connective tissue of ligaments. It is also continuous with one
Why is damaged cartilage not often repaired in adults?
There are relatively few chondrocytes to create type 2 collagen, so it is replaced with Type 1 collagen by fibroblasts (dense connective tissue)
What causes ossification?
When hyaline cartilage ossifies as part of the normal aging process
What tumors can form in cartilage?
Chondromas (benign), or chondrosarcomas (malignant)
What causes osteoarthritis?
Erosion of hyaline cartilage on articular surfaces (since there is no perichondrium to replace it). Cartilage is aneural, and when it is lost, surfaces of bones scraping produces intense pain.
More common in women
