Define connective tissue (as a general tissue type).
Connective tissue connects all the other cells of different tissue types both mechanically and metabolically. They are widely dispersed group ubiquitous throughout the entire body with different form and function. There are relatively few cells with much extracellular matrix between the cells.
List the developmental origin of all connective tissue.
They are all derived from the common origin of embryonic mesenchyme.
List and be able to classify the different types of CT as either CT proper or special CT.
There are three major types of connective tissue. There is embryonic connective tissues which include the mesenchymal connective tissue, consisting of the embryo and fetus. The mucous connective tissue consists of the umbilical cord.
The connective tissue proper is composed of loose (areolar) connective tissue, dense connective tissue, reticular tissue, and adipose tissue. Loose (areolar) connective tissue is the loose packing in most organs and tissues. It surrounds blood vessels. They have enough structure to hold an organ in place but allow movement. Dense connective tissue is made up of dense irregularCT (dermis, organ capsules, periosteum, preichondrium) and dense regular CT. The difference between areolar and dense is the number of extracellular fibers. The difference between irregular and regular is the structure. In dense irregular, interwoven collagen fibers run in all directions to resist weird forces and shear. Dense regular CT is all lined up and ordered. Dense regular CT can be either collagenous (tendons, ligaments, aponeurosis) or elastic (ligamentum nuchae, flaba). In the elastic, there is no collagen and it is much more dense. There are lots of them. Reticular tissue provides delicate support. It consists of lymphatic tissue and the bone marrow. Adipose tissue is found in small clu mps in normal connective tissue in addition to the subcutaneous layers you normally think of.
Specialized connective tissue is very unique due to its form and function. Cartilageis costal cartilage, trachea, pina, epiglottis. Bone as in the skeleton. Blood as in the cardiobascular system and the hematopoietic tissue. Fibrin fibers form blood clots.
List and describe the three major components common to all types of CT (cells, extracellular fibers, and ground substance; the last two make up the extracellular matrix).
Cells are subdivided into “fixed”, “wandering” or associated cells. Fixed cells are responsible for the sythesis and maintenance of the extracellular matrix of the particular connective tissue. Wandering cells are transient cells that migrate into and out of the extracellular matrix of the connective tissue. Associated cells are associated with the blood vessels that are always found surrounded and supported by the connective tissue.
Extracellular fibers include collagen fibers for strength, elastic fibers for stretch and flexibility, and reticular fibers for delicate support.
Ground substance is an amorphous material. It is a clear area that contains interstitial fluid, proteoglycans (complex macromolecules consisting of core protein with glycoaminoglycans (GAG's) attached to it), and glycoproteins (core protein with sugars attached to it, they form adhesion molecules).
Extracellular matrix is composed of the space between the cells. Take all the extracellular fibes and the ground substance. These fill the intercellular space.
List common locations in the body of each type of CT.
found in answer to objective three.
List and describe the three types of fibers in CT (collagen, reticular, and elastin). Classify the fibers according to size, morphology, chemical composition, and function.
Collagen fibers are the most abundant protein in the body. They have high tensile strength, are inelastic, but are flexible. The morphology of collagen is pretty comlicated but it is step by step so stay with it. Fasicles are bundles of fibers usually found in the connective tissue proper. Collagen fiber is straight, unbranched fibrous protein. It is made up of collagen fibrils, which are smaller and has same periodicity. Collagen fibrils are made up of tropocollagen molecules. Tropocollagen consists of three alpha polypeptide chains. They are rich in glycine, proline, hydroxyproline, and hydroxylysine. Hydrogen bonding between hydroxyproline molecules of adjacent polypeoptide chains hold the chains together. These tropocollagen molecules line up end to end and side by side in fibril to form collagen fibrils. The quarter stagger theory accounts for the lining up of the tropocollagen molecules in the fibril to give th fibril its periodicity. Covalent bonding between the hydroxylysine molecules in adjacent tropocollagen molecules hold the collagen fibril together. The most common types are I, II, III, and IV. Type I is for strength (found at dermis, bone, and tendons), type II resists pressure (found in elastic cartilage), type III provides a delicate support meshwork (lymphatic, spleen, cardiovascular network), and type IV provides for attachment filtration (basal lamina). The formation of collagen is a multiple step process that begins with transcription within nucleus. Then the proteins are translated within the rough ER. During translation, the hydroxylation of proline and lysine occurs. This allows the hydrogen bonding between the alpha fibers. Then procollagen is formed in rough ER. The procollagen is secreted via the Golgi apparatus. Procollagen peptidase cleaves the procollagen to form tropocollagen molecules outside the cell membrane. The tropocollagen molecules self assemble to form collagen fibril in the extracellular matrix. Lysyl oxidase covalently links hydroxylysine molecules of adjacent tropocollagen molecules to form insoluble fibrils. Collagen fibers are always turning over and they are broken down by collagenase. The elevated glycine in urine is indicative of collagen disease. Different diseases can result from erros in the collagen formation process. Scurvy is caused by a lack of vitamin C. Vitamin C is a cofactor required for the hydroxylation of proline. The procollagen fibers never maturely form. Ehlers-Danlos, Type VII is due to procollagen peptidase change. The procollagen can't self aggregate so they can never self assemple to form collagen fibril in the extracellular matrix. Diagnostic are hyperflexible joints, dislocations, soft skin.
Reticular fibers have a morphology of small branched fibers forming branched network. They are squiggly. Branching fibers intersect at right angles. They are argyophilic (silver loving) so they stain dark with silver. They provide delicate support and are often with lots of wandering cells. At the EM level, the fibers are composed of thin collagen type III fibrils covered with a sugar coat. Reticular cells wrap each fiber. Collagen cells are secreted in the same way as collagen fibers. They are located in regions with lots of wandering cells such as areolar connective tissue, reticular tissue, lyphatic tissue, liver, and hemopoietic tissue. The function is to provide delicate support. One disease involving reticular fibers is Ehler-Danlos type IV, which is due to a deficiency in type III collagen. This disease can cause aneurysms and intestinal rupture.
Elastic fibers are recognizable by a morphology of Y-branched fibers which form a continuous network within the tissue by fusing with adjacent fibers. They can also be found as sheets or lamella in large blood vessels. These can be stained black. The elastic fibers have two parts visible at the EM level. The amorphous componentconsists of elastin, which is the purified protein of the fiber. There is much glycine (kind of like collagen) but two unique amino acids are involved here: desmosine & isodesmosine. The microfibril component is a different glycoprotein. The function of elastic fibers is to stretch without breaking and spring back to original shape without using any muscle energy. Thesea re found in organs normally subjected to large amounts of strectching and repositioning. Examples include the blood vessels, aorta, lung, skin, ligamentum nuchae, and the uterus. They are formed like collagen. Proelastin is split to tropoelastin at cell membrane to elastic fibers outside the cell. Lysyl oxidase forms covalent cress links between tropoelastin molecules to form elastin in mesh of microfibrils. The elastic fiber system has three types of elastic fibers. Oxytalan fibers consist primarily of microfibrillar component. Eulanin fibers consist of microfibrils and some amorphous elastin. Elastic fibers (are made up of amourphous component and microbfibril component. Those are the ones we see above). Elastase breaks down elastic fibers for continuous turn over. Diseases involving elastic fibers include emphysema, lung dysfunction caused by break down of elastic fibers, and Marfan's Syndrome, caused by poor microfibril formation in elastic fiber-- this causes a weakened elastin. There is a tendency for patients with Marfan's to have ruptured aorta and other blood vessels.
Describe how the precursors of different fibers are secreted by the cell and aggregate to form the fiber outside of the cell. Be able to relate and describe diseases due to improper fiber formation.
Collagen's precursor is tropocollagen. This is made from procollagen outside the cell membrane. Procollagen is cleaved by procollagenpeptidase. The tropocollagen molecules self assemble to form collagen fibril in the extraceullar matrix. These collagen fibrils aggregate using lysyl oxidase, which covalently links hydroxylysine molecules of adjacent tropocollagen molcules to form collagen fibril in the extracellular matrix. Reticular fibers and elastic fibers are formed in similar ways to collagen fibers. They are all assembled outside of the cell. Lysyl oxidase is involved in the cross links to form final product (elastin, tropocollagen into insoluble fibrils)
Scurvy, caused by lack of Vitamin C (a cofactor required for hydroxylation of proline), prevents the protocollagen from even forming. The collagen “melts” and the capillaries break down. Scurvy is bad. Ehlers-Danlos, Type VII is due to procollagen peptidase change. The procollagen can't self aggregate so they never turn to tropocollagen. This is characterized by hyperflexible joints, dislocations, and soft skin. Ehlers-Danlos Type IV is due to a deficiency in type III collagen. This prevents the formation of reticular fibers, which are made up of thin collagen III fibrils covered with a sugar coat. Ehlers-Danlos Type IV clinically can manifest in aneyurysms and intestinal rupture. Emphysema is a lung dysfunction caused by a break down of the elastic fibers. Marfan's Syndrome is caused by poor microfibril formation in elastic fiber. There is a tendency to rupture aorta and other blood vessels due to the weakened elastin in the amorphous component of elastic fibers.
List and describe the components of the amorphous ground substance (water, proteoglycans, and glycoproteins). Relate these substances with their function within connective tissue.
Ground substance has no visible structure. What remains after the cells and extracellular fibers have been removed. There are three separate components that make up the ground substance: proteoglycans, insterstitial fluid, & glycoproteins.
Proteoglycans look a lot like a test tube brush. They have a protein core with glycosoaminoglycans (GAGs) attached. They form porous hydrated gel which is slippery and resists compression. Proteoglycans consist of sulfated and non-sulfated glycosaminoglycans (GAGs). In order to understand proteoglycans, you need to understand GAGs. GAGs are straight molecules of repeating disaccharides. There are six different GAGs. Hyaluronic Acid (HA) is the non-sulfated GAG. Large macromolecule with repeating disaccharides that are straight chains but highly coiled. This is a negatively charged molecule that holds H2O, Na+, and Ca++. Slippery and lubricating, hyaluronic acid has a gel-like consistency that resists compression. There are many channels allowing the diffusion of materials. They form a physical barrier that prevents the migration of bacteria through extracellular matrix. HA inhibits cell adhesion and facilitates cell migration. Higher levels of non-sulfated HA are present during embryogenesis and repair. Pathogens produce hyaluronidase which can digest hyaluronic acid and allows the pathogen to enter the cell. There are five sulfated GAGs. Keratan sulfate is located in the cartilage. Heparan sulfateis located in the basement membrane. Chondroitin-6-sulfate is located in the cartilage, skin, and bone. Chondroitin-4-sulfate is located in the cartilage, skin, and bone too. Dermatan sulfate is located in the dermis.
Proteoglycans can be divided into two types. Free proteoglycans and transmembrane PG's. Aggrecan is a free PG. It is free in the areolar CT matrix. It consists of a core protein with chondroitin sulfate and keratin sulfate attached. Aggrecan Aggregate is HA with hundreds of Aggrecan molecules. It is found in the cartilage matrix and is gel-like and compression resistant. Perlacan is another free proteoglycan (PG) that contains primarily heparin sulfate. It is found in the basal lamina. Syndecan is a transmembrane PG. One end of syndecan is in the cytoplasm and the other end is in the extracellular matrix. It is rich in heparin sulfate and chondroitin sulfate. Heparin sulfate binds to other PG's with heparin sulfate and chondroitin sulfate. Syndecan is not free in extracellular space. Fibroglycan is another transmembrane PG that is rich in heparin sulfate. Fibroglycan binds to three types of collagen and fibronectin.
Glycoproteins are smaller molecules. They consist of a protein core with branched sugars attached. They are adhesion molecules to help hold cells to the EMC. They bind to different GAG's and fibers. The glycoproteins are important for cell motility. Fibronectin is located in the basal lamina. It binds to heparin sulfate and collagen type IV. Fibronectin can be binding to syndecan or Fibroglycan. Laminin is located in the basement membrane. It binds to collagen IV and heparin sulfate. Entactin is located in the basement membrane. Entactin binds to laminin and collagen IV. Tenascin is located in the basement membrane. Tenascin binds to syndycan and fibronectin. Chondronectin is located in the cartilage matrix. Chondronectin binds cell integrin to collagen II. Oseonectin is located in the bone matrix. Osteonectin binds cell integrin to collagen I.
Interstitial fluid is the water found in the extracellular space. It is important in the transport of nutrients and wastes between blood vessels and the parenchyma. The fluid is bound by the proteoglycans and hyaluronic acid. Interstitial fluid is formed from when hydrostatic pressure on arterial end forces fluid out fo the capillary into the extracellular matrix. The fluid circulates through channels in HA & PG's towards the venous end of the capillary. Most fluid re-enters capillary due to higher oncotic pressure (due to loss of fluid) and large albumin molecules still in blood. There is always excess fluid left in the extracellular matrix, this is drained away in the lymphatic capillaries. Production and reabsorption of fluid creates continuous circulation through the exctracellular matrix. Interstitial fluid supplies nutrients and removes wastes from parenchymal cells.
Describe how the components of the extracellular matrix enable it to act as a medium for transfer of nutrients and wastes between the blood stream and any other cells or tissues.
The extracellular fibers doesn'y really play a strong role in the transfer of nutrients and waste. That role is primarily performed by the ground substance. Specifically the interstitial fluid is important in the transport of nutrients and wastes between blood vessels and the parenchyma. Water goes out of the capillary, does not go right back in but goes to the lymphatic system.
Describe the process of edema formation and relate this to the various causes of edema.
Edema is abnormal build up of interstitial fluid in the extracellular matrix. “Pitting edema” is where the push forms a pit. Some of the causes are: blocked lymphatics, blocked venous return, liver disease (albumin is produced by liver and pulls H2O back through the vessel), increased vascular permeability (histamine from mast cells), hypertension, or starvation (lack of plasma proteins). Myxedema is due to over production of GAGs during hypothyroidism.
Describe and understand the components of the basement membrane and relate its structure to its function.
The basement membrane is a light microscope term. The basement membrane functions to connect cells (epithelial, muscle, and nerve cells) to connective tissue. The basement membrane surrounds all cells except connective tissue cells (fixed and wandering) but there is another exception. The basement membrane does surround white adipose cells. At the EM level it is composed of three layers. The lamina lucida is a light layer next to the cell membrane. It contains integrins (from hemidesmisomes), laminin, and entactin. The lamina densa is a dense fuzzy band. The lamina densa contains collagen IV, perlacan (heparan sulfate) and fibronectin. Because of the latter two, glycoproteins bond to these. The lamina densa is negatively charged and acts as a flexible macromolecular filter. The lamina reticularis contains the reticular fibers (collagen III) and also IV and VII of anchoring fibrils. The basal lamina is just the lamina densa. This is in cells that there is a very reduced amount of lamina lucida, where it appears to have just a lamina densa. Most muscle cells look like this. The function of the basal lamina is to hold cells to the surrounding connective tissue and to act as a macromolecular sieve.
List and describe the morphology and function of each cell type normally found in connnective tissue. Classify the cell types as either “fixed”, “wandering”, or “associated.”
Fixed cells synthesize and maintain the extracellular matrix of a particular type of connnective tissue. Fibrocytes are the most common fixed cells of the connective tissue proper. They appear vesicular nuceus with nucleolus (they have hetero and euchromatin). You can't see the cytoplasm and the fibrocyte is a secretory cell (secretes fibers). The fibroblasts is the immature form that can undergo mitosis; the fibrocytes are mature and fully differentiated cells that can no longer divide. Mesenchymal cells look like fibroblasts. They are found in embryonic tissue and are pluripotent. Reticular cells are found in reticular tissue. The processes wrap around reticular fibers and form a cell-lined fiber network. Adipose cells are fixed cells in two different types of fat tissue. White Adipocytes are large and unilocular (single lipid droplet). Fat tissue is lacy and very light staining. They function in lipid storage. Lipid leaves the blood vessel and is broken down by Lipoprotein lipase, on endothelial cells, into free fatty acids and glycerol. The free fatty acids are taken up by adipocytes and complexed with glycerol to form neutral lipids (triglycerides). Stored lipids released by hormone sensitive lipase which breaks down triglycerides into free fatty acids that complex with albumin in blood to be transported around the body. Leptin is a protein produced by adipocytes tat targets the hypothalamus. Leptin decreases food intake and increases energy consumption. Insulin acts on adipocytes to form triglycerides from glucose, increases uptake of glucose and production of lipoprotein lipase. Epinephrine or norepinephrine stimulate hormone sensitive lipase system to mobilize fatty acids. Hypercellular obesity is an increased number of fat cells which is usually due to overfeeding as infant. Hypertrophic obesity is increased size (more lipid) in the same number of fat cells. This is the most common. Brown adipocytes are smaller with numerous mitochondria and are multilocular (numerous droplets of lipid in cytoplasm). They function to generate heat. Thermogenin is a mitochondrial membrane protein that permits the back flow of protons instead of using them for ATP production. Heat production is unique to brown fat and is used in babies to help maintain newborn's body temperature. Chondrocytes are the fixed cells in cartilage. Osteocytes are the fixed cells of bone tissue. Blood cells are the fixed cells of blodd.
Wandering cells are usually associated with the immune system: macrophages, mast cells, and plasma cells. All other leukocytes are also considered wandering cells. Macrophages are part of the mononuclear macrophage system. They are phagocytic cells that arise from monocytes (granulocytic-mononuclear stem cells) in the circulating blood. As the monocyte leaves the blood vessel and enters the extracellular matrix, it becomes a macrophage. The macrophage has different names based on the logan where it is located but they all serve the same function. One can only be sure a cell is a macrophage when it has ingested material such as a vital dye. They are oval, indented nucleus is visible with a vesicular chromatin pattern. The difference between the macrophage and fibroblast chromatin pattern is that the macrophage usually has more condensed chromatin than fibroblast nuclei. Lots of lysosomes are present in the macrophage. Mast cells are granular appearing, oval cells associated with small blood vessels. The nucleus is clear and mostly obscured by granules. The granule contents include mediators of the inflammatory response: heparin, histamine (vasodilator that causes increased vascular permeability and constriction of SMCs of the bronchioles), eosinophilic chemotaxic factor, neutrophilic chemotaxic factor, and also cause the secretion fo leukotrienes (C4 and D4, which have a histamine like effect but are long acting). Other things performed by the mast cells are the release of cytokines which can help identify spot of inflammation. The function of the mast cells is to store mediators fo inflammatory response. They bind IgE to its surface and then interacts with antigens. The first edxposure to antigen causes the formation of IgE's which bind to receptors on the mast cell surface. The second exposure has the antigen bind to IgE on the surface and activates adenyl cyclase. This causes phosphorylation of proteins that release Ca2+ that causes fusion fo granules and release of contents on surface. If too much Ca2+ is released, the patient can go into anaphylactic shock. The location of mast cells is along the capillaries in mucosal membranes in respiratory, digestive, and urinary tracts where antigens can easily enter. This is an example of paracrine secretion (it works locally). Plasma cells are a type of wandering cell with a morphology of an eccentric nucleus (pushed to one side of the cell) and a cartwheel chromatin pattern with hetero and euchromatin. There are lots of RER at the EM level because they produce the antibodies. They are normally found only in connective tissue, not in peripheral blood. They are derived from B-lymphocytes. The function of plasma cells is to produce antibodies.
Associated cells are found in blood vessels that are always surrounded by connective tissue. Endothelial cells are the lining of the blood vessel. Smooth muscle cells surround endothelium and control vessel size. Pericytes are multipotential stem cells for vessel repair and growth.
is a vague question about the amount and type of connective tissue. The big thing is structure determines function.
List the general functions of connective tissue.
CT is involved in support, medium for exchange between blood and tissues, storage, temperature regulation, mechanical protection, defense and repair.
Understand that adipose tissue is a special type of connective tissue. Identify the major cell type found in the two different types of adipose tissue and its function with its specific morphology. Be able to locate the two different types of adipose tissue within the body.
Adipose cells are fixed cells in two different types of fat tissue. White Adipocytes are large and unilocular (single lipid droplet). Fat tissue is lacy and very light staining. They function in lipid storage. Lipid leaves the blood vessel and is broken down by Lipoprotein lipase, on endothelial cells, into free fatty acids and glycerol. The free fatty acids are taken up by adipocytes and complexed with glycerol to form neutral lipids (triglycerides). Stored lipids released by hormone sensitive lipase which breaks down triglycerides into free fatty acids that complex with albumin in blood to be transported around the body. Leptin is a protein produced by adipocytes tat targets the hypothalamus. Leptin decreases food intake and increases energy consumption. Insulin acts on adipocytes to form triglycerides from glucose, increases uptake of glucose and production of lipoprotein lipase. Epinephrine or norepinephrine stimulate hormone sensitive lipase system to mobilize fatty acids. Hypercellular obesity is an increased number of fat cells which is usually due to overfeeding as infant. Hypertrophic obesity is increased size (more lipid) in the same number of fat cells. This is the most common. Brown adipocytes are smaller with numerous mitochondria and are multilocular (numerous droplets of lipid in cytoplasm). They function to generate heat. Thermogenin is a mitochondrial membrane protein that permits the back flow of protons instead of using them for ATP production. Heat production is unique to brown fat and is used in babies to help maintain newborn's body temperature.
Describe and identify the characteristic morphology and function of the specific (indiidual) types of connective tissue.
mucous CT: umbilical cord
mesenchme: embryo and fetus
dense irregular CT: interwoven collagen fibers run in any direction to resist forces and damage
dense regular CT: collagenous and elastic. All lined up and ordered.
elastic CT: uses elastin instead of collagen. Very dense, lots of them. Y-branched morphology. Stains dark in green. Orangish yellow in other stains. Found at blood vessels, aorta, lung, skin, and places that stretch.
reticular CT: branched at right angles. Stains dark in silver. Forms delicate support in areas with lots of wandering cells (areolar CT and reticular tissue).
adipose CT: unilocular or multilocular. Storage of lipids and heat production.