Ischemia-repurfusion Injuries Of The Appendicular Musculoskeletal System
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Ischemia-repurfusion Injuries Of The Appendicular Musculoskeletal System
Ischemia-reperfusion (IR) tissue injury is the resultant pathology from a combination of factors, including tissue hypoxia, followed by tissue damage associated with re-oxygenation. IR injury contributes to disease and mortality in a variety of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Whether resulting from traumatic vessel disruption, tourniquet application, or shock, the extremity is exposed to an enormous flux in vascular perfusion during a critical period of tissue repair and regeneration. The contribution of this ischemia and subsequent reperfusion on post-traumatic musculoskeletal tissues is unknown; however, it is likely that similar to cardiac and kidney tissue, IR significantly contributes to tissue fibrosis. Definitions * "Ischemia": an inadequate blood supply to an organ or part of the body. * " Reperfusion": the restoration of blood flow to an organ or tissue afte ...
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Tissue Hypoxia
Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either '' generalized'', affecting the whole body, or ''local'', affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.. Hypoxia differs from hypoxemia and anoxemia, in that hypoxia refers to a state in which oxygen present in a tissue or the whole body is insufficient, whereas hypoxemia and anoxemia refer specifically to states that have low or no oxygen in the blood. Hypoxia in which there is complete absence of oxygen supply is referred to as anoxia. Hypoxia can be due to external causes, when the breathing gas is hypoxic, or internal causes, such as reduced effectiveness of gas transfer in the lungs, reduced capacity of the blood to carry oxygen, compromised general ...
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Fasciotomy
Fasciotomy or fasciectomy is a surgical procedure where the fascia is cut to relieve tension or pressure in order to treat the resulting loss of circulation to an area of tissue or muscle. Fasciotomy is a limb-saving procedure when used to treat acute compartment syndrome. It is also sometimes used to treat chronic compartment stress syndrome. The procedure has a very high rate of success, with the most common problem being accidental damage to a nearby nerve. Indications Compartment syndrome is one of the conditions where a fasciotomy may be indicated. People who are likely to have injuries needing a fasciotomy include the following: * Crush injuries * Athletes who have sustained one or more serious impact injuries * People with severe burns * People who are severely overweight * Snakebite victims, but very rarely Complications A delay in performing the procedure can lead to neurovascular complications or lead to the need for amputation of a limb. Complications can also invo ...
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Reperfusion Therapy
Reperfusion therapy is a medical treatment to restore blood flow, either through or around, blocked arteries, typically after a heart attack (myocardial infarction (MI)). Reperfusion therapy includes drugs and surgery. The drugs are thrombolytics and fibrinolytics used in a process called thrombolysis. Surgeries performed may be minimally-invasive endovascular procedures such as a percutaneous coronary intervention (PCI), which involves coronary angioplasty. The angioplasty uses the insertion of a balloon to open up the artery, with the possible additional use of one or more stents. Other surgeries performed are the more invasive bypass surgeries that graft arteries around blockages. If an MI is presented with ECG evidence of an ST elevation known as STEMI, or if a bundle branch block is similarly presented, then reperfusion therapy is necessary. In the absence of an ST elevation, a non-ST elevation MI, known as an NSTEMI, or an unstable angina may be presumed (both of these a ...
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Cardiomyocyte
Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall (the pericardium) and the inner layer (the endocardium), with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix. Cardiac muscle contracts in a similar manner to skeletal muscle, although with some important differences. Electrical stimulation in the form of a cardiac action potential triggers the release of calcium from the cell's internal calcium store, the sarcoplasmic reticulum. The rise in calcium causes the cell's my ...
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Cyclosporine A
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, and in organ transplants to prevent rejection. It is also used as eye drops for keratoconjunctivitis sicca (dry eyes). Common side effects include high blood pressure, headache, kidney problems, increased hair growth, and vomiting. Other severe side effects include an increased risk of infection, liver problems, and an increased risk of lymphoma. Blood levels of the medication should be checked to decrease the risk of side effects. Use during pregnancy may result in preterm birth; however, ciclosporin does not appear to cause birth defects. Ciclosporin is believed to work by decreasing the function of lymphocytes. It does this by forming a complex with cyclophilin to block the phosphatase activity of calcineuri ...
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Cyclophilin D
Peptidylprolyl isomerase D (cyclophilin D), also known as PPID, is an enzyme which in humans is encoded by the ''PPID'' gene on chromosome 4. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to facilitate folding or repair of proteins. In addition, PPID participates in many biological processes, including mitochondrial metabolism, apoptosis, redox, and inflammation, as well as in related diseases and conditions, such as ischemic reperfusion injury, AIDS, and cancer. Structure Like other cyclophilins, PPID forms a β-barrel structure with a hydrophobic core. This β-barrel is composed of eight anti-parallel β-strands and capped by two α-helices at the top and bottom. In addition, the β-turns and loops in the strands contribute to the flexibility of the barrel. PPID in particular is composed of 370 residues and shares structural homology with PPIF, FKBP4, and ...
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Mitochondrial Permeability Transition Pore
The mitochondrial permeability transition pore (mPTP or MPTP; also referred to as PTP, mTP or MTP) is a protein that is formed in the inner membrane of the mitochondria under certain pathological conditions such as traumatic brain injury and stroke. Opening allows increase in the permeability of the mitochondrial membranes to molecules of less than 1500 Daltons in molecular weight. Induction of the permeability transition pore, mitochondrial membrane permeability transition (mPT or MPT), can lead to mitochondrial swelling and cell death through apoptosis or necrosis depending on the particular biological setting. Roles in pathology The MPTP was originally discovered by Haworth and Hunter in 1979 and has been found to be involved in neurodegeneration, hepatotoxicity from Reye-related agents, cardiac necrosis and nervous and muscular dystrophies among other deleterious events inducing cell damage and death. MPT is one of the major causes of cell death in a variety of conditions. ...
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Mitochondrial Matrix
In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions. /sup> The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids. The composition of the matrix based on its structures and contents produce an environment that allows the anabolic and catabolic pathways to proceed favorably for. The electron transport chain and enzymes in the matrix play a large role in the citric acid cycle and oxidative phosphorylation. The citric acid cycle produces NADH and FADH2 through oxidation that will be reduced in oxidative phosphorylation to produce ATP. The cytosolic, in ...
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Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from Cellular respiration, oxidative metabolism causes base damage, as well as DNA damage (naturally occurring), strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O2− (superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the ...
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Cell Therapy
Cell therapy (also called cellular therapy, cell transplantation, or cytotherapy) is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues. Cell therapy originated in the nineteenth century when scientists experimented by injecting animal material in an attempt to prevent and treat illness. Although such attempts produced no positive benefit, further research found in the mid twentieth century that human cells could be used to help prevent the human body rejecting transplanted organs, leading in time to successful bone marrow transplantation as has become common practice in treatment for patients that have compromised bone marrow after disease, infection, radiation or chemotherapy. In recent decades, however, stem cell and cel ...
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O-ring
An O-ring, also known as a packing or a toric joint, is a mechanical gasket in the shape of a torus; it is a loop of elastomer with a round cross-section, designed to be seated in a groove and compressed during assembly between two or more parts, forming a seal at the interface. The O-ring may be used in static applications or in dynamic applications where there is relative motion between the parts and the O-ring. Dynamic examples include rotating pump shafts and hydraulic cylinder pistons. Static applications of O-rings may include fluid or gas sealing applications in which: (1) the O-ring is compressed resulting in zero clearance, (2) the O-ring material is vulcanized solid such that it is impermeable to the fluid or gas, and (3) the O-ring material is resistant to degradation by the fluid or gas. The wide range of potential liquids and gases that need to be sealed has necessitated the development of a wide range of materials. O-rings are one of the most common seals used i ...
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Resuscitative Endovascular Balloon Occlusion Of The Aorta
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive procedure performed during resuscitation of critically injured trauma patients. Originally developed as a less invasive alternative to emergency thoracotomy with aortic cross clamping, REBOA is performed to gain rapid control of non-compressible truncal or junctional hemorrhage. REBOA is performed first by achieving access to the common femoral artery (CFA) and advancing a catheter within the aorta. Upon successful catheter placement, an occluding balloon may be inflated either within the descending thoracic aorta (Zone 1) or infrarenal abdominal aorta (Zone 3). REBOA stanches downstream hemorrhage and improves cardiac index, cerebral perfusion, and coronary perfusion. Although REBOA does not eliminate the need for definitive hemorrhage control, it may serve as a temporizing measure during initial resuscitation. Despite the benefits of REBOA, there are significant local and systemic ischemic ...
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