Amyloidosis - a disease that has a detrimental effect on your body at the cellular sublayer.In the course of certain reactions in the tissue cells about to pathological protein and slowly, cell by cell, deletes the entire organ structure.
Amyloidosis is dangerous not only for its common manifestations as local lesions.To be precise, amyloidosis affects important functional structures of the body: the liver, heart and kidneys.And as any manifestation of amyloidosis, sooner or later it will end the destruction of the normal structure of the body, then, respectively, in the body there were serious violations of the internal homeostasis.
Amyloidosis in its classification is divided into smaller sub-species.They are usually distinguished by bodies that affects amyloidosis, and because of its appearance.According to the etiology of the existing primary and the secondary amyloidosis.Primary amyloidosis is a disease exclusively associated with gene disorders.It is this type of amyloid
also amyloidosis can be divided into the form on the prevalence of protein deposits in tissues: systemic amyloidosis (generalized) and local.
Localization in the affected organs are the following subtypes: renal amyloidosis, amyloidosis of the liver, cardiac amyloidosis, amyloidosis of the intestine, skin amyloidosis.The most frequently met and hazards of renal amyloidosis, liver and heart.
renal amyloidosis is often a secondary amyloidosis.Also in the kidneys is delayed only one subspecies of amyloid protein - AA amyloid.When renal amyloidosis distinctive feature is that the cells that synthesize the amyloid, are mesangial cells in glomeruli.Besides dramatically increased the amount of protein - the progenitor of AA amyloid in the blood plasma.In turn, the progenitor of amyloid with the blood enters the glomerulus of the kidneys to filter blood.There he is captured by special cells and mesangial cells used for the construction of new structures of amyloid.
Thus, for renal amyloidosis has two mechanisms create abnormal protein directly into kidney structures: changing mesangial cell function and production of amyloid precursor amyloid levels increase in the plasma and maintain them additional mezangiotsitah protein synthesis.As a result, the amount of AA amyloid to be enormous.
Of course, this level of amyloid will not affect the body in a positive way, and even more so in the normal renal function.This amyloid is deposited in the cells, gradually leading to their death and subsequently death of the entire organ.Mesangial cells from amyloid spread, and will hit the cells of the basal membrane, through which the blood tends to filtration through the capillaries, as well as the same basement membrane tubules.
addition of basal membranes another favorite place of amyloid deposits are arterioles.As a result of these actions nephrons (structural units of the kidney) will atrophy and die one by one.In place of the dead bodies will be synthesized connective tissue and the kidney itself, as it were reduced in size (amyloid "wrinkled" kidney).
amyloidosis in the kidneys excrete stage, which simultaneously will coincide with changes in the kidneys, and external clinical processes.These stages are classified from low to high on the development process.
first stage of renal amyloidosis is the latent stage of change.When it gradually fills the amyloid protein pyramid (microstructure of the kidneys), proximal channels and collecting ducts.There still may not experience pronounced insufficiency of renal function, but in the analysis of urine can already be found above normal protein (proteinuria).Its main feature is that it will rise during exercise, and because of the appearance of colds.Plus, in the analysis of urine protein component will be revealed a sharp imbalance between the individual protein fractions.
proteinuric stage events will follow for the next stage of the above renal amyloidosis.When it amyloid will gradually capture glomerular kidney structures.Fill it will be a mesangium, capillary loops and arterioles.It is at this stage of renal amyloidosis sclerosis will begin to develop their individual structures (mostly been above the pyramid).As a result, the neurons begin to shut down and broken blood and lymph flow.This will lead to the beginning of degenerative changes in the kidneys.
In the clinic the patient will appear proteinuria, which, unlike proteinuria latent stage, will be a constant and does not depend on any external conditions.Also proteinuria still easy to find an imbalance of proteins.New manifestations will appearance cylinders (protein casts in the tubules are formed) and a small amount of red blood cells in the urine (hematuria).
On stage nephrotic amount of amyloid lesions in the renal structures continues to increase.It captures most of the glomeruli of the kidney.Continue to appear sleroticheskie defeat kidney medulla.The clinic will appear edema.The peculiarity of these swellings that they do not disappear after the administration of diuretics.All of the above will also be changes in the urine only become massive proteinuria.To edema in patients will be added, and a significant reduction in blood pressure.
and last stage of renal amyloidosis - stage azotemia or uremia (similar to those in patients with renal insufficiency).Amyloid sclerosis affects all layers of the kidney.Most nephrons die and are replaced by connective tissue.In clinical syndromes are all associated with renal insufficiency.Incidentally, renal failure, and is a major cause of death in patients with renal amyloidosis.She threatens them at almost every stage of the disease.In fact, these patients literally every day, sitting on the "powder keg."
At amyloidosis of the heart abnormal protein structures deposited in it.Most often it is deposited in the myocardium, endocardial cells.Also, this protein does not bypass the attention and vessels: it can be deposited in the aorta or coronary vasculature of the heart.The most common cardiac amyloidosis develops in the types of amyloidosis, AL-containing protein.
main mechanisms in amyloidosis of the heart are units in which the synthesis of amyloid AL-structures.Their detailed pathogenesis is written below, but generally speaking, this protein is synthesized in the synthesis due to violations of the right immune cells.This amyloid accumulates in the blood and, apparently, is carried through the bloodstream to organs.Once in the heart, it is deposited primarily in the myocardium, and it accumulates between muscle cells.Incidentally, the constant accumulation of amyloid in the myocardium leads to the fact that its increased weight compresses intramural arteries and arterioles, and causes a lack of nutrition in the heart muscle.
Filled amyloid myocardium becomes very dense, and most importantly, it loses its ability to stretch.As a result of reduced cardiac output, impaired heart function, heart failure develops gradually.
If amyloid is deposited in the main valve near the machine, it will cause a bright clinic valvular.That is, the clinical symptoms of heart amyloidosis depends on the place where deposited amyloid: so for example, if the structure of amyloid appears beside pathways, it shows signs of conduction disturbances, especially the blockade.
cardiac amyloidosis is characterized by slow, long course, its symptoms can develop over a sufficiently long time.The disease manifests itself dramatically after suffering respiratory infections, stress, overexertion.You may see a sharp drop in pressure, severe pain, like stenokardicheskie or will develop syncope.An important feature is also a selective reduction of pressure in the upright position.
If the disease develops slowly, gradually will develop classic symptoms of heart failure: shortness of breath, swelling, enlargement of the liver.Such heart failure hardly responds to treatment with cardiac glycoside.
amyloidosis of the heart is also very often accompanied by pericardial effusions in the bag, as well as the rapid development of ascites.As described above, are shown and irregularities in the conduction system of the heart: blockade, and especially the specific sinus syndrome.This syndrome amyloidosis in patients can lead to sudden cardiac death.
amyloidosis of the liver almost never occurs by itself.Most often it occurs with the same amyloid lesions in other organs: the spleen, kidneys, adrenal glands or intestine.
Rather, it is the cause of immunological disorders or severe purulent infectious and inflammatory diseases.The clearest sign of the manifestation of the disease will increase in the liver and spleen.Very rarely it is accompanied by what a pain symptoms or jaundice.This disease is characterized by worn clinic and slow progression.In the last stages of the disease may develop multiple symptoms of hemorrhagic syndrome.In these patients very quickly reduce the protective function of immunity, and they will be vulnerable to any kind of infections.
also characteristic changes in amyloidosis of the liver exposed skin - it becomes pale and dry.Possible manifestations of portal hypertension and subsequent liver cirrhosis: amyloidosis gradually kills hepatocytes, and are replaced by connective tissue.
The most dangerous complication of these patients will develop liver failure and hepatic encephalopathy.
causes of amyloidosis depends on its subspecies.If the primary amyloidosis, the reason for its occurrence lies exclusively in the genetic code of its own mistakes.This type of amyloidosis is transmitted genetically, there are even entire families where all the members suffer from primary amyloidosis.
secondary amyloidosis, as has been described above, it is a consequence of primary diseases.More often than not lead to the appearance of his rheumatoid arthritis and ankylosing spondylitis.Also at high risk are amyloidosis end UC (ulcerative colitis) and Crohn's disease.High ability to stimulate the development of amyloidosis have lymphoma and Hodgkin's disease.Also, pathological conditions such as chronic suppurative inflammatory diseases and osteomyelitis, too, can easily lead to the first signs of secondary amyloidosis.
Greater risk of developing amyloidosis are also subject to those patients who for some reason are on dialysis system.Most often, of course, is ill with chronic renal failure.This is because a certain protein by dialysis does not pass through the membrane device, it accumulates in the body and gradually accumulates in the cells of the tissue.After a while, this protein will form the basis for amyloidosis.
By amyloidosis can also cause some tumors.It is a cancer of the pancreas, cancer of the thyroid gland, pituitary adenoma and parathyroid glands.The peculiarity of this amyloidosis is that the cancer cells of these organs affects the special system (APUD).As a result of the aggression of cancer cells, these cells are destroyed APUD, and their remains are the basis for the formation of amyloid protein.
But besides the main causes (etiology) amyloidosis, and is also important to know the basic laws and mechanisms that occur in this disease.Please be aware that each type of amyloidosis occurs in its own way.The pathogenesis is assumed to specify the types of amyloidosis on its basic protein.The most important are amyloidosis, containing a protein AA (the one that causes renal amyloidosis described above) and amyloidosis AL with the protein.
Although different proteins, amyloidosis can be isolated and the main stage of the process:
- preparation.At this stage, there is a mutation of cells retikuloendotelioidnoy structure, and there are cells - synthesizers amyloid (amiloidoblasty).It is important to say that each type of amyloid his mother cells (such as macrophages or cells of kidney mesangial)
- Development of the mother cell protein amyloid and the subsequent assembly of its structures
- The final formation of the structure of the pathological protein to which it is connected with special proteinsblood or tissue factors
Interestingly, during this course a little bit similar to a subtype in the course of multiple myeloma.There just is a violation of developing the "right» B-lymphocytes and appear abnormal B-lymphocytes, which are beginning to develop a chain of future amyloid.Only in multiple myeloma the chains called heavy, but here, in amyloidosis, immunoglobulin light chains are synthesized.Then, the chain no longer be converted into normal immunoglobulins, fall and collect some amyloid structure.
is believed that the main cause of this type of amyloidosis is a decrease in T-lymphocytes and thus reduces the number of cells controllers T-suppressors, which can inhibit the abnormal B lymphocytes.Standing synthesize pathological chain also contributes to the fact that the cell - amyloid clone loses its ability to cell death.This type of amyloidosis is considered imunnozavisimym.
AA amyloidosis containing
to this subtype is characterized by the presence of the mother cell, which synthesizes the precursor protein substance SAA.These parent cells are macrophages of the liver, spleen or mesangial cells from renal amyloidosis.In the initial stage the cells intensively synthesized substance.Due to the fact that much of this substance, it is not completely converted into amyloid - amyloid maternal cells collected from separate fragments of the substance.Gradually, during the subsequent stages of the whole substance goes into molecules of amyloid assembly.
In this form of amyloidosis have a certain regularity.First - is that the amount of amyloid is directly dependent on the amount of substance precursor generating the higher its synthesis, the greater will be synthesized and amyloid itself.The second rule is that when AA amyloidosis disturbed relationship between the functional activity of the cells that synthesize amyloid and amyloid-absorbing cells: last function is greatly reduced.This means that there is less disruption of the amyloid protein, and it is deposited in tissues.
Symptoms of amyloidosis depends on the subspecies.For example, when the local amyloidosis are characteristic signs of the functions of individual organs: heart, liver or kidney failure.
also often affected skeletal muscles.Myshtsy increase in its volume, due to amyloid deposits therein.It develops so-called fake malnutrition (psevdogipotrofiya).Furthermore muscles become more dense.
also frequently affected the gastrointestinal tract (e.g., the above-described amyloidosis liver).Also amyloidosis of the liver may be affected muscles of the tongue.At the same time it develops its increase - macroglossia or "big tongue".This symptom develops a quarter of patients with amyloidosis.This is a pretty serious symptom, for a significant increase in the amount of language can cause breathing difficulties.Besides language amyloidosis also likes to hit the esophagus or intestine.With the defeat of the esophagus may develop serious violations, until the complete narrowing of its lumen and the inability to pass on the raw-food chyme.
When intestinal cells are affected, then there are a symptom of how the well-known and diarrhea.In most cases, it appears with amyloidosis of the fact that the amyloid structures located close to the nerve endings of the fibers in the intestine and exert on them a permanent stimulus.If you were impressed by amyloidosis cells of the small intestine, then there will be dysfunction syndrome intestinal absorption.