Connective tissue, as the name implies, is a term given to several different tissues of the body that serve to connect, support and help bind other tissues in the body. Connective tissue can further be broken down into three categories: loose connective tissue, dense connective tissue, and specialized connective tissue. Loose connective tissue works to hold organs in place and is made up of extracellular matrix and collagenous, elastic and reticular fibers. Dense connective tissue is what makes up tendons and ligaments and consist of a higher density of collagen fibers. Examples of specialized connective tissues are adipose tissue, cartilage, bone, blood, and lymph.
Loose and dense connective tissue are made up of the following three fibers: collagen fibers, reticular fibers, and elastin fibers.
Collagen fibers are made up of closely packed thin collagen fibrils that run a wavy course in tissues. These parallel fibrils are bundles with flexible proteoglycans to offer an essential mechanical property. They offer flexible but powerful resistance to pulling force. Specifically, in loose connective tissue, collagen runs in a parallel course and then joins to form a larger bundle. They split from each other and join back together at varying locations creating a three-dimensional meshwork. Dense connective tissue such as ligaments and tendons are compromised mainly of densely packed collagen fibers.
Reticular fibers, also called argyrophilic fibers, have a restricted abundance in the human body. They are primarily present in basement epithelial tissue, adipose cells, Schwann and muscle cells, lymphoid tissue and endothelium of hepatic sinusoids. Under microscopy, these reticular fibers are fine, dark fibrils that are continuous with the college fibers described above. The arrangement of these fibers forms a network that underlies the basal lamina layer. There is a firm attachment of these fibers to the basal lamina that indicates that, along with the collagen fibers, these fibers create a functional and structural unit that serves to support tissues. The loose arrangement of these fibers also provides space for molecular movement within the extracellular fluid.
The last component to discuss is elastin fibers. These fibers have the characteristic property of elastic recoil. Typically, in loose connective tissue, elastin is a loose network. Their organization and distribution depend on the type of tissue. Concentric elastin fibers are present in the vascular wall to help maintain uniform blood pressure. Fibers are also present in distensible and contractible organs such as the lungs and urinary bladder.
Connective tissue arises from the somatic mesoderm. Inductive signals from nearby sclerotome and myotome cause an upregulation expression of a key transcription factor in tenogenic and ligamentogenic differentiation called scleraxis. Several fibroblast factors as well as transforming growth factor-beta have involvement in regulating tendon development. Tendon progenitor cells begin to lay down collagenous fibrils, and these fibrils grow in different directions and beginning to form the tendon fascicle. Tendon fibroblasts reside between collagen fibers. A connective tissue layer called the epitenon surrounds these tendon fascicles to form the complete tendon tissue.
Different types of connective tissue have a variable blood supply. Tendons and ligaments, in particular, appear partially avascular. They are compromised mainly of densely packed collagen fibers which undergo no metabolic activity and don’t require a blood supply. There are living cells hidden within these collagen fibers which require blood supply; however, their volume is minimal as compared to the tendons as a whole.
All peripheral nerve fibers consist of three connective tissue layers which serve as a protective connective sheath. Epineurium is the outer most layer of dense connective tissue that encloses the entire peripheral nerve. Within the epineurium, there are several nerve fascicles which are individually enclosed by the perineum. These fascicles are made up of myelinated individual nerve fibers that are surrounded by endoneurium.
Individual muscles cells are grouped together to form a fiber. These fibers are further bundled together to form a fascicle, and several of these fascicles get further grouped together to create the entire muscle. Connective tissue exists between every muscle cell, fiber, and fascicle. At a molecular level, each muscle cell is connected to other muscle cells by a collagenous basement membrane called an endomysium. The fascicles are surrounded by perimysium which further connects to the epimysium which encompasses the entire skeletal muscle and is continuous with the tendon. The collagenous network beginning at the level of the endomysium is continuous with the perimysium and the tendon, which allows for an effective and powerful muscle contraction.
The following are a pair of examples of clinically significant connective tissue conditions:
Mixed Connective Tissue Disease
Mixed connective tissue disease (MCTD) is an autoimmune connective tissue disorder characterized by an autoantibody to ribonucleoprotein (RNP). It presents clinically as SLE, systemic sclerosis, and polymyositis. Diagnostic criteria are based on anti-RNP serology with myositis or synovitis plus two of the following: edema of hands, Raynaud’s phenomenon, sclerodactyly/acrosclerosis. Pulmonary symptoms are prevalent in patients with MCTD. Patients may complain of cough, dyspnea or pleuritic chest pain. Pulmonary hypertension is the most severe pulmonary consequence and often leads to premature death.
Rotator Cuff Injury
The rotator cuff is comprised of four tendons localized in the shoulder region. These tendons originate from the following muscles: subscapularis, supraspinatus, infraspinatus, and teres minor. Rotator cuff injuries can present as debilitating pain, reduced shoulder movement and function, and shoulder weakness. Treatment is started initially with physical therapy and corticosteroid injections. Surgical techniques are also available for patients that have failed conservative therapy; however, research has demonstrated an equivocal benefit with the surgical approach. Patients with rotator cuff tendon injuries are at increased risk for repeated tears through their lifetime.
|||Ushiki T, Collagen fibers, reticular fibers and elastic fibers. A comprehensive understanding from a morphological viewpoint. Archives of histology and cytology. 2002 Jun; [PubMed PMID: 12164335]|
|||Yang G,Rothrauff BB,Tuan RS, Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth defects research. Part C, Embryo today : reviews. 2013 Sep; [PubMed PMID: 24078497]|
|||EDWARDS DA, The blood supply and lymphatic drainage of tendons. Journal of anatomy. 1946 Jul; [PubMed PMID: 20996686]|
|||Liu Q,Wang X,Yi S, Pathophysiological Changes of Physical Barriers of Peripheral Nerves After Injury. Frontiers in neuroscience. 2018; [PubMed PMID: 30210280]|
|||Light N,Champion AE, Characterization of muscle epimysium, perimysium and endomysium collagens. The Biochemical journal. 1984 May 1; [PubMed PMID: 6743238]|
|||Pepmueller PH, Undifferentiated Connective Tissue Disease, Mixed Connective Tissue Disease, and Overlap Syndromes in Rheumatology. Missouri medicine. 2016 Mar-Apr; [PubMed PMID: 27311225]|