Interstitium

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Interstitium
Anatomical terminology
Three-dimensional schematic of the interstitium, a fluid-filled space supported by a network of collagen Intersticio (organo).jpg
Three-dimensional schematic of the interstitium, a fluid-filled space supported by a network of collagen

The interstitium is a contiguous fluid-filled space existing between a structural barrier, such as a cell membrane or the skin, and internal structures, such as organs, including muscles and the circulatory system. [1] [2] The fluid in this space is called interstitial fluid, comprises water and solutes, and drains into the lymph system. [2] The interstitial compartment is composed of connective and supporting tissues within the body – called the extracellular matrix – that are situated outside the blood and lymphatic vessels and the parenchyma of organs. [2] [3] The role of the interstitium in solute concentration, protein transport and hydrostatic pressure impacts human pathology and physiological responses such as edema, inflammation and shock. [4]

Contents

Structure

The non-fluid parts of the interstitium are predominantly collagen types I, III, and V, elastin, and glycosaminoglycans, such as hyaluronan and proteoglycans that are cross-linked to form a honeycomb-like reticulum. [3] Collagen bundles of the extracellular matrix form scaffolding with a high tensile strength. Interstitial cells (e.g., fibroblasts, dendritic cells, adipocytes, interstitial cells of Cajal and inflammatory cells, such as macrophages and mast cells), serve a variety of structural and immune functions. [3] [4] Fibroblasts synthesize the production of structural molecules as well as enzymes that break down polymeric molecules. [3] Such structural components exist both for the general interstitium of the body, [2] and within individual organs, such as the myocardial interstitium of the heart, [5] the renal interstitium of the kidney, [6] and the pulmonary interstitium of the lung.

The interstitium in the submucosae of visceral organs, the dermis, superficial fascia, and perivascular adventitia are fluid-filled spaces supported by a collagen bundle lattice. Blind end, highly permeable, lymphatic capillaries extend into the interstitium. The fluid spaces communicate with draining lymph nodes, although they do not have lining cells or structures of lymphatic channels. [7] Interstitial fluid entering the lymphatic system becomes lymph, which is transported through lymphatic vessels until it empties into the microcirculation and the venous system. [4]

Functions

The interstitial fluid is a reservoir and transportation system for nutrients and solutes distributing among organs, cells, and capillaries, for signaling molecules communicating between cells, and for antigens and cytokines participating in immune regulation. [2] The structure of the gel reticulum plays a role in the distribution of solutes across the interstitium, as the microstructure of the extracellular matrix in some parts excludes larger molecules (exclusion volume). The density of the collagen matrix fluctuates with the fluid volume of the interstitium. Increasing fluid volume is associated with a decrease in matrix fiber density, and a lower exclusion volume. [8] [3]

The total fluid volume of the interstitium during health is about 20% of body weight, but this space is dynamic and may change in volume and composition during immune responses and in conditions such as cancer, and specifically within the interstitium of tumors. [2] The amount of interstitial fluid varies from about 50% of the tissue weight in skin to about 10% in skeletal muscle. [2] Interstitial fluid pressure is variable, ranging from -1 to -4 mmHg in tissues like the skin, intestine and lungs to 21 to 24 mmHg in the liver, kidney and myocardium. Generally, increasing interstitial volume is associated with increased interstitial pressure and microvascular filtration. [8]

The renal interstitium facilitates solute and water transport between blood and urine in the vascular and tubular elements of the kidneys, and water reabsorption through changes in solute concentrations and hydrostatic gradients. [9] [10] The myocardial interstitium participates in ionic exchanges associated with the spread of electrical events. [11] The pulmonary interstitium allows for fluctuations in lung volume between inspiration and expiration. [12]

The composition and chemical properties of the interstitial fluid vary among organs and undergo changes in chemical composition during normal function, as well as during body growth, conditions of inflammation, and development of diseases, [2] as in heart failure [5] and chronic kidney disease. [6]

Disease

In people with lung diseases, heart disease, cancer, kidney disease, immune disorders, and periodontal disease, the interstitial fluid and lymph system are sites where disease mechanisms may develop. [2] [5] [6] [13] Interstitial fluid flow is associated with the migration of cancer cells to metastatic sites. [2] [14] The enhanced permeability and retention effects refers to increased interstitial flow causing a neutral or reversed pressure differential between blood vessels and healthy tissue, limiting the distribution of intravenous drugs to tumors, which under other circumstances display a high-pressure gradient at their periphery. [14]

Changes in interstitial volume and pressure play critical roles in the onset of conditions like shock and inflammation. [3] [4] During hypovolemic shock, digestive enzymes and inflammatory agents diffuse to the interstitial space, then drain into the mesenteric lymphatic system and enter into circulation, contributing to systemic inflammation. [4] Accumulating fluid in the interstitial space (interstitial edema) is caused by increased microvascular pressure and permeability, a positive feedback loop mechanism resulting in an associated in increasing the rate of microvascular filtration into the interstitial space. [4] Decreased lymphatic drainage due to blockage can compound these effects. Interstitial edema can prevent oxygen diffusion across tissue and in the brain, kidney and intestines lead to the onset of compartment syndrome. [4]

See also

Related Research Articles

<span class="mw-page-title-main">Human body</span> Entire structure of a human being

The human body is the entire structure of a human being. It is composed of many different types of cells that together create tissues and subsequently organs and then organ systems. They ensure homeostasis and the viability of the human body.

<span class="mw-page-title-main">Capillary</span> Smallest type of blood vessel

A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the site of the exchange of many substances from the surrounding interstitial fluid, and they convey blood from the smallest branches of the arteries (arterioles) to those of the veins (venules). Other substances which cross capillaries include water, oxygen, carbon dioxide, urea, glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in microcirculation.

<span class="mw-page-title-main">Edema</span> Accumulation of excess fluid in body tissue

Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area may feel heavy, and joint stiffness. Other symptoms depend on the underlying cause.

<span class="mw-page-title-main">Lymphatic system</span> Organ system in vertebrates complementary to the circulatory system

The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lymphatic tissue and lymph. Lymph is a clear fluid carried by the lymphatic vessels back to the heart for re-circulation. The Latin word for lymph, lympha, refers to the deity of fresh water, "Lympha".

<span class="mw-page-title-main">Extracellular matrix</span> Network of proteins and molecules outside cells that provides structural support for cells

In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.

<span class="mw-page-title-main">Connective tissue</span> Type of biological tissue in animals

Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesoderm, the middle embryonic germ layer. Connective tissue is found in between other tissues everywhere in the body, including the nervous system. The three meninges, membranes that envelop the brain and spinal cord, are composed of connective tissue. Most types of connective tissue consists of three main components: elastic and collagen fibers, ground substance, and cells. Blood, and lymph are classed as specialized fluid connective tissues that do not contain fiber. All are immersed in the body water. The cells of connective tissue include fibroblasts, adipocytes, macrophages, mast cells and leukocytes.

<span class="mw-page-title-main">Body fluid</span> Liquids inside of the body, sometimes excreted or secreted

Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the body of an organism. In lean healthy adult men, the total body water is about 60% (60–67%) of the total body weight; it is usually slightly lower in women (52–55%). The exact percentage of fluid relative to body weight is inversely proportional to the percentage of body fat. A lean 70 kg (150 lb) man, for example, has about 42 (42–47) liters of water in his body.

<span class="mw-page-title-main">Lymph</span> Fluid that circulates throughout the lymphatic system

Lymph is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to be recirculated. At the origin of the fluid-return process, interstitial fluid—the fluid between the cells in all body tissues—enters the lymph capillaries. This lymphatic fluid is then transported via progressively larger lymphatic vessels through lymph nodes, where substances are removed by tissue lymphocytes and circulating lymphocytes are added to the fluid, before emptying ultimately into the right or the left subclavian vein, where it mixes with central venous blood.

<span class="mw-page-title-main">Extracellular fluid</span> Body fluid outside the cells of a multicellular organism

In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 50–60% of total body weight; women and the obese typically have a lower percentage than lean men. Extracellular fluid makes up about one-third of body fluid, the remaining two-thirds is intracellular fluid within cells. The main component of the extracellular fluid is the interstitial fluid that surrounds cells.

<span class="mw-page-title-main">Lymphatic vessel</span> Tubular vessels that are involved in the transport of lymph and lymphocytes

The lymphatic vessels are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessels are lined by endothelial cells, and have a thin layer of smooth muscle, and adventitia that binds the lymph vessels to the surrounding tissue. Lymph vessels are devoted to the propulsion of the lymph from the lymph capillaries, which are mainly concerned with the absorption of interstitial fluid from the tissues. Lymph capillaries are slightly bigger than their counterpart capillaries of the vascular system. Lymph vessels that carry lymph to a lymph node are called afferent lymph vessels, and those that carry it from a lymph node are called efferent lymph vessels, from where the lymph may travel to another lymph node, may be returned to a vein, or may travel to a larger lymph duct. Lymph ducts drain the lymph into one of the subclavian veins and thus return it to general circulation.

<span class="mw-page-title-main">Fibrosis</span> Excess connective tissue in healing

Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue.

The Starling principle holds that extracellular fluid movements between blood and tissues are determined by differences in hydrostatic pressure and colloid osmotic (oncotic) pressure between plasma inside microvessels and interstitial fluid outside them. The Starling Equation, proposed many years after the death of Starling, describes that relationship in mathematical form and can be applied to many biological and non-biological semipermeable membranes. The classic Starling principle and the equation that describes it have in recent years been revised and extended.

<span class="mw-page-title-main">Loose connective tissue</span> Type of connective tissue in animals

Loose connective tissue, also known as areolar tissue, is a cellular connective tissue with thin and relatively sparse collagen fibers. They have a semi-fluid matrix with lesser proportions of fibers. Its ground substance occupies more volume than the fibers do. It has a viscous to gel-like consistency and plays an important role in the diffusion of oxygen and nutrients from the capillaries that course through this connective tissue as well as in the diffusion of carbon dioxide and metabolic wastes back to the vessels. Moreover, loose connective tissue is primarily located beneath the epithelia that cover the body surfaces and line the internal surfaces of the body. It is also associated with the epithelium of glands and surrounds the smallest blood vessels. This tissue is thus the initial site where pathogenic agents, such as bacteria that have breached an epithelial surface, are challenged and destroyed by cells of the immune system.

<span class="mw-page-title-main">Interstitial nephritis</span> Medical condition

Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubules. It is also known as intestinal nephritis because the clinical picture may include mesenteric lymphadenitis in some cases of acute pyelonephritis. More specifically, in case of recurrent urinary tract infection, secondary infection can spread to adjacent intestine. In addition to providing a scaffolding support for the tubular architecture, the interstitium has been shown to participate in the fluid and electrolyte exchange as well as endocrine functions of the kidney.

Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells.

<span class="mw-page-title-main">Lymph capillary</span> Microvessel serving to drain and process extracellular fluid

Lymph capillaries or lymphatic capillaries are tiny, thin-walled microvessels located in the spaces between cells which serve to drain and process extracellular fluid. Upon entering the lumen of a lymphatic capillary, the collected fluid is known as lymph. Each lymphatic capillary carries lymph into a lymphatic vessel, which in turn connects to a lymph node, a small bean-shaped gland that filters and monitors the lymphatic fluid for infections. Lymph is ultimately returned to the venous circulation.

The human body and even its individual body fluids may be conceptually divided into various fluid compartments, which, although not literally anatomic compartments, do represent a real division in terms of how portions of the body's water, solutes, and suspended elements are segregated. The two main fluid compartments are the intracellular and extracellular compartments. The intracellular compartment is the space within the organism's cells; it is separated from the extracellular compartment by cell membranes.

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<span class="mw-page-title-main">Glymphatic system</span> System for waste clearance in the central nervous system of vertebrates

The glymphatic system is a system for waste clearance in the central nervous system (CNS) of vertebrates. According to this model, cerebrospinal fluid (CSF) flows into the paravascular space around cerebral arteries, combining with interstitial fluid (ISF) and parenchymal solutes, and exiting down venous paravascular spaces. The pathway consists of a para-arterial influx route for CSF to enter the brain parenchyma, coupled to a clearance mechanism for the removal of interstitial fluid (ISF) and extracellular solutes from the interstitial compartments of the brain and spinal cord. Exchange of solutes between CSF and ISF is driven primarily by arterial pulsation and regulated during sleep by the expansion and contraction of brain extracellular space. Clearance of soluble proteins, waste products, and excess extracellular fluid is accomplished through convective bulk flow of ISF, facilitated by astrocytic aquaporin 4 (AQP4) water channels.

<span class="mw-page-title-main">Meningeal lymphatic vessels</span>

The meningeal lymphatic vessels are a network of conventional lymphatic vessels located parallel to the dural venous sinuses and middle meningeal arteries of the mammalian central nervous system (CNS). As a part of the lymphatic system, the meningeal lymphatics are responsible for draining immune cells, small molecules, and excess fluid from the CNS into the deep cervical lymph nodes. Cerebrospinal fluid, and interstitial fluid are exchanged, and drained by the meningeal lymphatic vessels.

References

  1. ↑ Bert JL; Pearce RH (1984). The interstitium and microvascular exchange. In: Handbook of Physiology. The Cardiovascular System. Microcirculation (sect. 2; pt. 1; chapt. 12; vol. IV ed.). Bethesda, MD: American Physiological Society. pp. 521–547. ISBN   0-683-07202-1.
  2. 1 2 3 4 5 6 7 8 9 10 Wiig, H; Swartz, M. A (2012). "Interstitial fluid and lymph formation and transport: Physiological regulation and roles in inflammation and cancer". Physiological Reviews. 92 (3): 1005–60. doi:10.1152/physrev.00037.2011. PMID   22811424.
  3. 1 2 3 4 5 6 Scallan J; Huxley VH; Korthuis RJ (2010). The Interstitium. In: Capillary Fluid Exchange: Regulation, Functions, and Pathology. San Rafael, CA: Morgan & Claypool Life Sciences. Archived from the original on 2021-02-08. Retrieved 2018-03-29.
  4. 1 2 3 4 5 6 7 Stewart, Randolph H. (2020-11-05). "A Modern View of the Interstitial Space in Health and Disease". Frontiers in Veterinary Science. 7. doi: 10.3389/fvets.2020.609583 . ISSN   2297-1769. PMC   7674635 . PMID   33251275.
  5. 1 2 3 Eckhouse SR; Spinale FG (2012). "Changes in the myocardial interstitium and contribution to the progression of heart failure". Heart Fail Clin. 8 (1): 7–20. doi:10.1016/j.hfc.2011.08.012. PMC   3227393 . PMID   22108723.
  6. 1 2 3 Zeisberg, M; Kalluri, R (2015). "Physiology of the Renal Interstitium". Clinical Journal of the American Society of Nephrology. 10 (10): 1831–1840. doi:10.2215/CJN.00640114. PMC   4594057 . PMID   25813241.
  7. ↑ Benias, Petros C.; Wells, Rebecca G.; Sackey-Aboagye, Bridget; Klavan, Heather; Reidy, Jason; Buonocore, Darren; Miranda, Markus; Kornacki, Susan; Wayne, Michael (2018-03-27). "Structure and Distribution of an Unrecognized Interstitium in Human Tissues". Scientific Reports. 8 (1): 4947. Bibcode:2018NatSR...8.4947B. doi:10.1038/s41598-018-23062-6. ISSN   2045-2322. PMC   5869738 . PMID   29588511.
  8. 1 2 Stewart, Randolph H. (2020-11-05). "A Modern View of the Interstitial Space in Health and Disease". Frontiers in Veterinary Science. 7. doi: 10.3389/fvets.2020.609583 . ISSN   2297-1769. PMC   7674635 . PMID   33251275.
  9. ↑ Moe, Orson W.; Giebisch, Gerhard H.; Seldin, Donald W. (2009), "Logic of the Kidney", Genetic Diseases of the Kidney, Elsevier, pp. 39–73, doi:10.1016/b978-0-12-449851-8.00003-6, ISBN   978-0-12-449851-8 , retrieved 2024-04-22
  10. ↑ Breshears, Melanie A.; Confer, Anthony W. (2017). The Urinary System. Elsevier. pp. 617–681.e1. doi:10.1016/b978-0-323-35775-3.00011-4. PMC   7271189 .
  11. ↑ Haschek, Wanda M.; Rousseaux, Colin G.; Wallig, Matthew A. (2010), "Cardiovascular and Skeletal Muscle Systems", Fundamentals of Toxicologic Pathology, Elsevier, pp. 319–376, doi:10.1016/b978-0-12-370469-6.00012-x , retrieved 2024-04-22
  12. ↑ Matthes, Stephanie A.; Hadley, Ryan; Roman, Jesse; White, Eric S. (2015). Comparative Biology of the Normal Lung Extracellular Matrix - Chapter 20. Elsevier. pp. 387–402. doi:10.1016/b978-0-12-404577-4.00020-5.
  13. ↑ Berggreen, E; Wiig, H (2014). "Lymphatic function and responses in periodontal disease". Experimental Cell Research. 325 (2): 130–7. doi:10.1016/j.yexcr.2013.12.006. PMID   24503053.
  14. 1 2 Munson, Jennifer; Shieh, Adrian (2014-08-01). "Interstitial fluid flow in cancer: implications for disease progression and treatment". Cancer Management and Research: 317. doi: 10.2147/CMAR.S65444 . ISSN   1179-1322. PMC   4144982 . PMID   25170280.
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