Histology: Connective Tissue

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Questions and Answers

What is the functional significance of the spatial arrangement of collagen fibrils in dense regular connective tissue, particularly in tendons and ligaments, considering the biomechanical properties arising from this organization?

  • It reduces the tissue's overall tensile strength, but enhances its elasticity, enabling it to withstand frequent deformations.
  • It increases the tissue's compressive strength, allowing it to withstand high impact loads without deformation.
  • It allows for multidirectional resistance to tensile forces, preventing tissue tearing under complex loading conditions.
  • It provides maximal resistance to unidirectional tensile forces along the longitudinal axis, optimizing for efficient force transmission. (correct)

Given the diverse array of collagen types, proteoglycans, and glycoproteins present in the extracellular matrix (ECM) of connective tissues, what biophysical principle governs the self-assembly and hierarchical organization of these components into functional architectures?

  • The principle of 'tensegrity,' wherein a balance of tensile and compressive forces distributed throughout the ECM network dictates its structural integrity and responsiveness to mechanical stimuli. (correct)
  • The principle of 'ablative morphogenesis,' wherein differential degradation of ECM components by matrix metalloproteinases (MMPs) sculpts the tissue architecture.
  • The principle of 'chaotropic scaffolding,' wherein hydrophobic interactions drive the alignment of ECM components along pre-existing cellular templates.
  • The principle of 'stochastic entanglement,' wherein random collisions between ECM components result in the formation of stable, albeit non-specific, cross-links.

How do fibroblasts orchestrate the dynamic remodeling of the extracellular matrix (ECM) during tissue repair, considering the interplay between matrix synthesis, degradation, and cross-linking?

  • By solely relying on mechanical forces transmitted through integrins to rearrange pre-existing ECM fibers without altering their composition.
  • By passively responding to signals from immune cells that dictate the composition and architecture of the newly synthesized ECM.
  • By constitutively secreting a uniform cocktail of matrix metalloproteinases (MMPs) that non-selectively degrade all ECM components.
  • By precisely regulating the expression and activity of matrix metalloproteinases (MMPs) and lysyl oxidases to locally degrade and cross-link ECM components in a spatiotemporally controlled manner. (correct)

In the context of connective tissue extracellular matrix (ECM) organization, what is the critical role of fibronectin in mediating cellular interactions and matrix assembly, considering its multi-domain structure and ligand-binding promiscuity?

<p>Fibronectin acts as a 'molecular Velcro,' bridging cells and other ECM components through its ability to simultaneously bind to integrins, collagens, and glycosaminoglycans, thereby facilitating cell adhesion, migration, and matrix assembly. (B)</p> Signup and view all the answers

How does the interplay between glycosaminoglycans (GAGs), such as hyaluronan and chondroitin sulfate, and proteoglycans influence the hydration and biomechanical properties of connective tissues, considering their distinct chemical structures and water-binding capacities?

<p>GAGs, with their highly negative charge, attract and retain water molecules, creating a hydrated, gel-like matrix that resists compressive forces, while proteoglycans modulate the spacing and organization of collagen fibers within this hydrated environment. (C)</p> Signup and view all the answers

What is the functional relevance of the differential distribution of collagen types (e.g., type I, type II, type III, type IV) in various connective tissues, considering their distinct fibril-forming properties and interactions with other matrix components?

<p>The specific collagen type is dependent on the tissue, e.g. type I provides tensile strength in tendons, type II in cartilage resists compression, with type III providing structural support in highly cellular tissues. (A)</p> Signup and view all the answers

Given the known roles of matrix metalloproteinases (MMPs) in ECM remodeling, how is the activity of these enzymes tightly regulated in vivo to prevent uncontrolled tissue degradation and maintain tissue homeostasis, in light of their destructive potential?

<p>MMPs are synthesized as inactive pro-enzymes (zymogens) that require proteolytic activation, and their activity is further regulated by specific inhibitors (TIMPs) and growth factors, ensuring localized and temporally controlled ECM remodeling. (B)</p> Signup and view all the answers

Considering the complex process of collagen fibrillogenesis, how do post-translational modifications, such as hydroxylation and glycosylation, influence the stability and mechanical properties of collagen fibrils, and what are the enzymatic mechanisms involved?

<p>Hydroxylation of proline residues, catalyzed by prolyl hydroxylases, is essential for stabilizing the collagen triple helix, while glycosylation regulates fibril diameter and interactions with other matrix components. (D)</p> Signup and view all the answers

How do mechanical forces influence fibroblast behavior and ECM remodeling in connective tissues, considering the role of mechanotransduction pathways and the ability of fibroblasts to sense and respond to changes in their mechanical environment?

<p>Mechanical forces, transduced through integrins and other mechanosensors, regulate fibroblast adhesion, migration, proliferation, and ECM synthesis and degradation, thereby orchestrating tissue remodeling in response to mechanical demands. (A)</p> Signup and view all the answers

Given the clinical significance of excessive ECM deposition in fibrotic diseases, what are the key cellular and molecular mechanisms that drive the transition of fibroblasts into myofibroblasts, and how do these cells contribute to tissue stiffening and organ dysfunction?

<p>Myofibroblasts arise through the activation of quiescent fibroblasts by profibrotic cytokines (e.g., TGF-β), leading to increased α-smooth muscle actin (α-SMA) expression, enhanced ECM synthesis, and contractile force generation, resulting in tissue stiffening and organ dysfunction. (D)</p> Signup and view all the answers

Elastin is critical for tissue elasticity, yet its production declines with age. What are the implications of this age-related decline in elastin synthesis on the biomechanical properties of tissues, particularly in blood vessels and skin, and what molecular mechanisms contribute to this phenomenon?

<p>The age-related decline in elastin leads to decreased elasticity and increased stiffness in tissues such as blood vessels and skin, due to reduced tropoelastin synthesis, increased elastin degradation by elastases, and impaired crosslinking of elastin fibers. (D)</p> Signup and view all the answers

How do reticular fibers contribute to the structural organization and function of lymphoid organs and bone marrow, considering their unique composition and interactions with immune cells?

<p>Reticular fibers, composed of type III collagen, form a delicate meshwork that supports immune cells, guides their migration, and facilitates cell-cell interactions within lymphoid organs and bone marrow. (B)</p> Signup and view all the answers

What signaling pathways regulate the synthesis and deposition of basement membrane components, and how do these pathways coordinate the interactions between epithelial cells and the underlying connective tissue stroma?

<p>Signaling pathways, involving growth factors (e.g., TGF-β, VEGF) and integrins, regulate the synthesis and deposition of basement membrane components (e.g., laminin, collagen IV, nidogen) and coordinate epithelial-stromal interactions by modulating cell adhesion, migration, and differentiation. (B)</p> Signup and view all the answers

Given the role of proteoglycans in regulating growth factor availability and signaling, how do specific proteoglycans, such as decorin and perlecan, modulate cellular responses to growth factors in the context of tissue development and repair?

<p>Decorin binds to TGF-β and inhibits its activity, while perlecan sequesters FGFs and presents them to their receptors, thereby modulating cellular responses to these growth factors during development and repair. (C)</p> Signup and view all the answers

What differences exist between the molecular structures of the different glycosaminoglycans (GAGs) and how do these structural differences influence their interactions with other extracellular matrix components?

<p>Different GAGs consist of differing levels of monosaccharides, leading to differences interactions, contributing to different ECM organization. (C)</p> Signup and view all the answers

Considering the diverse functions of glycoproteins in the ECM, what specific roles do tenascins play in regulating cell adhesion, migration, and tissue remodeling, particularly during development and wound healing?

<p>Tenasins, as matricellular proteins, modulate cell adhesion and migration by interacting with integrins and growth factors, and orchestrate tissue remodeling during development and wound healing through their ability to promote both cell adhesion and detachment. (B)</p> Signup and view all the answers

Given the destructive potential of matrix metalloproteinases (MMPs), how do tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity to prevent excessive ECM degradation and maintain tissue homeostasis?

<p>Tissue inhibitors of metalloproteinases (TIMPs) tightly regulate the activity of MMPs by binding to their active sites and non-covalently blocking their activity. (B)</p> Signup and view all the answers

What is the molecular basis for the mechanical properties of elastin, considering its unique amino acid composition and the presence of cross-linking amino acids such as desmosine and isodesmosine?

<p>The mechanical properties are based on the ability of hydrophobic regions that are stretched to allow it to function, and cross-linking amino acids allow them to stretch and relax. (D)</p> Signup and view all the answers

How do the unique structural properties of reticular fibers, characterized by their argyrophilia and association with type III collagen, contribute to their function in supporting hematopoietic and lymphoid tissues?

<p>The unique structural properties with argyrophilia and the association with type III collagen aids in supporting tissues. (B)</p> Signup and view all the answers

What are the key molecular differences between different types of elastic fibers (e.g., oxytalan, elaunin, and mature elastic fibers), and how do these differences relate to their distinct mechanical properties and distribution in various tissues?

<p>Different molecular weight affects the location that the elastic function occurs. (B)</p> Signup and view all the answers

Flashcards

Extracellular Matrix Functions

Provides resistance, elasticity and hydration to tissues; depends on the matrix composition.

Fibroblasts

Synthesize the extracellular matrix

Adipocytes

Stores fat (triglycerides)

Macrophages

Carry out phagocytosis

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Mast Cells

Important in inflammatory responses

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Fibronectin

Attaches basal lamina to the lamina propria.

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Laminins

Major component of the basal lamina.

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Collagen

Most abundant protein in the body.

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Collagen in Bones, Tendons, Ligaments, Skin

Collagen Type I

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Hyaline Cartilage

Collagen Type II

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Elastin Fibers

Small fibers provide elasticity in tissues; main component is tropoelastin.

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Reticular fibers

Provide a supportive framework in organs.

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Proteoglycans & GAGs

Provide resistance and hydration

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GAGs Negative Charges

Allow water molecules to associate strongly; increases hydration.

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Glycoproteins

Adhesion to the matrix; bind cells to the matrix.

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Metalloproteinases

Remodels the matrix

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Loose Connective Tissue

Has fewer collagen fibers and more ground substance.

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Dense Irregular Tissue

Has disorganized fibers

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Dense Regular Tissue

Has organized fibers

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Embryonic Connective Tissue

Found in the embryo and umbilical cord; also known as mesenchyme.

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Study Notes

  • Histology examines connective tissue

Connective Tissue

  • A magistral plan covers loose connective tissues, including adipose, reticular, areolar, and mucous types
  • Includes mesenchymal cells, fibroblasts, unilocular and multilocular adipocytes, macrophages, plasma cells, and mast cells
  • Also includes loose connective tissues of subcutaneous fat

Cells

  • Study of fixed and errant cells

Fixed Cells

  • Fibroblasts synthesize the ECM (extracellular matrix)
  • Cytes are more specialized and do not produce as much extracellular matrix
  • Chondroblasts become chondrocytes, osteoblasts become osteocytes, and cell names change depending on the tissue
  • Adipocytes store fat as triglycerides
  • Macrophages perform phagocytosis
  • Mast cells are important in inflammatory responses

Errant Cells

  • Neutrophils
  • Eosinophils
  • Basophils
  • Lymphocytes
  • Monocytes

Extracellular Matrix Functions

  • Functions include providing tissue properties like resistance, hardness, elasticity, hydration, and optical characteristics, depending on its composition
  • Maintains integrity and provides mechanical properties to tissues
  • Influences cell shape and allows intercellular communication
  • Forms pathways for cell movement and modulates cell differentiation and physiology
  • Sequester growth factors
  • Fibronectin unites cells and aligns them to the EMC

Signals

  • Tissue is stimulated by factors for differentiation, survival, migration, and proliferation

Organization

  • Basal lamina: connects to the lamina propria via proteins anchored to hemidesmosomes
  • Lamina lucida: adheres to the epithelium via integrins and entactin (nidogen)
  • Nidogen mediates lamina and collagen IV union
  • Lamina densa mainly consists of collagen IV
  • Lamina reticularis: fibers consist of collagen III
  • Fibers of collagen
  • Glycoproteins
  • Elastic fibers

Fibers

Collagen

  • Represents 25-30% of body's proteins
  • There are 46 genes and 28 types
  • Provides support to tissues and resists tensile forces
  • Glycine allows for arrangement into left-handed helices
  • Collagen type III is very important
  • Synthesized by reticular cells, fibroblasts, and myofibroblasts
  • Functions in mechanical support against tension and traction
  • Found around nerve tissue, blood vessels, uterus, and intestines
  • Fibers surround adipocytes and are within lymph nodes, myocardium, and liver

Elastin

  • Fibers have the capacity for distension and relaxation
  • Found in tissues requiring these functions and has a net shape
  • Primary component is tropoelastin(90%)
  • Elastic properties come from hydrophobic amino acids
  • Globular and elastic in aquatic environments, as well as stretching under mechanical force
  • Located in the dermis, elastic cartilage, connective tissue of lungs, and concentration reduces over time
  • Can be found in blood vessels, mostly in the aorta
  • Support tissues and regulate growth factor activity, TGF-mediated by fibrillin

Reticular

  • Metallic dye is used
  • Metallic dye is used

Other Components.

  • Proteoglycans consist of polypeptide + glucosaminoglycans (heparan sulfate, chondroitin/dermatan, and queratan)
  • They bind through serine amino acids
  • Examples include agrecan (cartilage), brevican and neurocranin (nervous tissue), versican (connective tissue)
  • SRLP proteoglycans have many leucine repeats and are attached to chondroitin, dermatan sulfate, or queratan sulfate
  • SRLP stabilizes collagen fibers
  • Hydrates and offers resistance in mechanical environments, lubricate, affect cell development, movement, and physiology

-Glicosaminoglicanos

  • Gives resistance to pressure and cushions blows
  • Has more glycosaminicans
  • Non-branching sugar polymers form long chains
  • Negative charges allows water molecules to tightly bind, increasing hydration
  • Provides hydration to the matrix
  • Resists strong pressure and allows material to diffuse throughout cell
  • Hyaluronic acid or hyaluronate associates with collagen or proteoglycans
  • Hyaluronic acid is important where there is cellular proliferation because it eases cellular displacement
  • Important where strong friction happens, as in cartilage

-Glycoproteins

  • Adhere to the extracellular matrix and hold cells to the matrix
  • Fibronectins bind collagen, proteoglycans, glycosaminoglycans, fibrin, heparin, and integrins, and connect cells with the ECM
  • Laminins comprise the main component of the basal lamina, synthesized by epithelial and muscle cells, neurons, and bone marrow cells
  • Tenascins change ECM cohesion by forming bonds with integrins, fibronectins, collagens, and proteoglycans
  • Osteopontin is present in bone and relates to mineralization and bone remodeling and can found in the kidney
  • Fibulin associates with the basal lamina and elastic fibers.

-Metalloproteinases

  • Degrade and Remodel the extracellular matrix produced by fibroblasts, epithelial cells, chondrocytes, osteoclasts, leukocytes, and tumors

Connective Tissue Types

Loose

  • Fewer collagen fibers
  • Found under epithelia with lots of fundamental substance
  • Spaces appear due to cells suspended in water and fixed with ground substance
  • Types include areolar

Dense Irregular

  • Less fundamental substance and fewer cells than loose connective
  • Fibers disorganized
  • Surrounds organs and divides
  • Contains collagen I and III

Dense Regular

  • Fibers are highly organized making it very resistant
  • Found in ligaments and tendons

Embryonic

  • Found in embryos and umbilical cord
  • Called mesenchymal or mucoid connective tissue, as cells go on to become many tissue types

Reticular

  • Reticular cells produce reticular fibers of collagen III
  • Located in lymphatic tissue
  • It is the support (stromal) tissue

Adipose

  • Primarily accumulates triglycerides, either white (unilocular) or brown (multiocular)
  • Cartilage and bone
  • Hylaine collagen type II cartilage is more hydrated, with proteoglycans

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