Amyloidosis

Amyloidosis - usually a general disease characterised by extracellular deposit of the special eosinophilic protein, differing by origin, - an amyloid causing disturbances of function of various organs. The amyloid is a complex glycoproteid in which fibrillar and globular proteins are closely bound to polysaccharides. By means of a submicroscopy and X-ray diffraction methods orderliness of a constitution of an amyloid, presence in it of fibrillar structures are accurately shown. The dimensions of fibrils compound 7,5 - 10 nanometers in a diameter and to 800 nanometers at length. The fibril consists of polypeptide chains with crossbetaconformstion, that defines double refraction at a coloration red, inherent to an amyloid. Except a fibrous protein, the amyloid structure includes other protein - so-called P-component which is identical at all forms of an amyloidosis. Role P-component in amyloidogenesis is obscure. Probably, it is normal serum protein which contacts amyloid fibrils.

Aetiology and pathogenesis. Depending on an aetiology and features of a pathogenesis excrete the idiopathic (primary), got (secondary), hereditary (genetical), local amyloidosis, an amyloidosis at a multiple myeloma and an APUD-amyloidosis. Most often there is a secondary amyloidosis, which by origin comes nearer to nonspecific (in particular immune) to reactions. It educes at a pseudorheumatism, ankylosing spondylitis, a tuberculosis, chronic pyeses - an osteomyelitis, a bronchoectatic disease, is rarer at a lymphogranulomatosis, tumours of a nephros, a lung and other organs, a syphilis, a nonspecific ulcerative colitis, Whipple's disease, a subacute infectious endocarditis, a psoriasis, etc. Casuistry rarely the amyloidosis is observed at diffusive illnesses of a copulative tissue, a sarcoidosis.

Hereditary amyloidosis is usually bound to periodic illness which is transferred on an autosomno-dominant type. At this disease the amyloidosis can be unique implication. There are other forms of a hereditary amyloidosis less often.

Unlike a secondary and hereditary amyloidosis at a primary amyloidosis to establish the cause or hereditary character of disease it is not possible. On structure of an amyloid and character of a lesion of an internals the amyloidosis is close to a primary amyloidosis at a multiple myeloma with which excrete in separate bunch. The aorta, heart, pancreas recently pay attention to amyloidosis development at senile age (especially at persons is more senior 70 - 80 years) when are amazed a brain. Describe new forms of an amyloidosis, in particular an amyloidosis at the patients who are on a chronic hemodialysis, characterised by a destructive arthropathy, a syndrome of the carpal canal and osteal defects. The question on mutual relation between an amyloidosis and an atherosclerosis remains till now open though there are indicatings, that atheromatous changes can promote amyloid deposit.

APUD - An amyloidosis - the special kind of the local endocrine form of an amyloidosis at which formation of the basic component of an amyloid fibril descends from products of vital activity of cells APUD - systems (apudocides) that is characteristic for tumours - apudomas. To APUD - to an amyloidosis carry an amyloidosis of a stroma of a medullary cancer of a thyroid gland, islets of pancreas, an adenoma of epithelial bodies, a pituitary body, and also the isolated senile amyloidosis of auricles.

Recently it is offered to section an amyloidosis on biochemical structure of amyloid fibrils.

An AA amyloid is most often meeting amyloid protein which analogue in Serum is protein SАА. The given type of amyloid protein find at a secondary amyloidosis and an amyloidosis at periodic illness. Its serumal precursor (SАА) is protein which appears in blood serum at an acute inflammation, tumours, pregnancy, rheumatic diseases and other states. It is shown, that protein SАА is synthesised by hepatocytes, the initiator of its synthesis is the interleukine 1.

АF-amyloid tap at hereditary forms of an amyloid polyneuropathy. It is possible to assume, that serumal precursor АF is one of polymorphic forms of normal prealbumin. АL- amyloid consists from Ig and fragments of light chains Ig.

In the eighties at patients, it is long being on a hemodialysis, have started to tap often a syndrome of the carpal canal amyloid deposit in a synovial membrane (An - amyloid) was which cause. The serumal precursor of this type of amyloid protein is β₂ microglobulin.

АS-amyloid is observed at clinically heterogenous bunch of patients of advanced age. The serumal precursor of the given type of amyloid protein is prealbumin.

Clinical picture. Clinical implications of an amyloidosis are various and depend on localisation of amyloid deposits, their prevalence. The localised forms of an amyloidosis, for example a skin amyloidosis, longly proceed asymptomatically, as well as a senile amyloidosis at which amyloid deposits in a brain, pancreas, heart quite often find only on dissecting.

Lesion of nephroses observe usually at a secondary amyloidosis, is rarer at primary and hereditary. The amyloid is postponed in the beginning in a mesangium of glomuluses, then along basal membranes. Gradual diffusion of amyloid deposits and involving to process of a vascular side leads to development of the basic implications amyloidosis of kidneys - an accruing proteinuria with occurrence of a nephrotic syndrome, renal insufficiency, sometimes to an arterial hypertensia. The nephrotic syndrome is observed at 50 - 60 % of patients. Usually it educes gradually after rather long stage of a moderate proteinuria. At some patients appearance of the nephrotic syndrome provoked by an intercurrent infection contamination, refrigerating, a trauma, medicinal materials, bacterination or a basic disease exacerbation, can seem subitaneous.

Long loss of protein by the nephroses, reaching 20 - 40 grammes/days, and also a number of other factors (albuminolysis intensifying in an organism, reduction of an absorption and, hence, the enhanced deducing of proteins through a gastrointestinal tract) lead to development of a hypoalbuminemia and the hydropic syndrome bound to it. A combination of a massive proteinuria to the big edemas - a characteristic clinical sign of an amyloidosis of nephroses. As a rule, edemas educe early and get the widespread and persistent character; they remain appreciable even in the terminal uremic season and differ resistance to diuretics. As implication of the expressed disproteinemia at the majority of patients is noted by the ESR substantial growth, the variated sedimental assays, augmentation of the maintenance of β₂ globulins.

Often tap a nonperishable microhematuria, sometimes a gross hematuria which forces to spend additional inspection for a tumour exception.

The leukocyturia meets quite often and without a concomitant pyelonephritis. The lesion of the canalicular apparatus of nephroses is studied a little.

Amyloid deposit in marrow of nephroses can lead to a nephrogenic diabetes insipidus, disturbance of a reabsorbtion of water in collective tubes, to the canalicular acidosis which is not giving in to correction by bicarbonate. Chronic renal insufficiency at an amyloidosis it is characterised by slowly educing azotemia, it is frequent in a combination to the expressed proteinuria and frequent absence of an arterial hypertensia.

Among other implications of an amyloidosis it is necessary to note a lesion of heart which is especially characteristic for a primary amyloidosis. The basic implications of an amyloidosis of heart - the rhythm and conductivity disturbances, a progressing heart failure, the cardialgias caused, apparently, by a lesion of fine coronary arteries. On electrocardiogram find depression of a voltage of a teeth, infarction-like changes. At an echocardiography tap a sharp thickening and myocardium inspissation, reduction of the dimension of a lumen of a left ventricle. As a result of a lesion of adrenals at an amyloidosis the arterial hypotension educes.

The lesion gastrointestinal tract can show in an initial stage an abdominal distention, appetite depression. The state of patients considerably worsens at development of the sprue leading to a sharp weight loss, changes of a vodno-electrolytic exchange. Sometimes owing to a long diarrhoeia edemas considerably decrease.

The liver and lien amyloidosis usually is not accompanied by essential disturbance of function of these organs, except often found rising of level of an alkaline phosphatase of blood at amyloid deposit in a liver. In 2/3 cases tap liver augmentation, in 1/3 - liens. At an amyloidosis peripheric lymph nodes can be amazed also.

At a pancreas lesion development of a latent diabetes and change of activity of pancreatic enzymes are possible.

The neurologic semiology inherent to separate forms of a hereditary primary amyloidosis, at a secondary amyloidosis can appear in a terminal (uremic) stage of illness.

At an amyloidosis the fibrinosis, a thrombocytosis, an anaemia (are observed also more often at Chronic renal insufficiency or as disease implications at which the amyloidosis has educed), a medullar plasmocytosis, maintenance rising hexosamines and depression of level of calcium of blood.

Diagnosis and Differential diagnosis. The amyloidosis should be suspected in the presence of a nephropathy, a nonperishable serious heart failure, a sprue, a polyneuropathy which it is difficult to explain other causes. Anyway in the presence of a nephrotic syndrome at adults it is necessary, besides a glomerulonephritis, to exclude and an amyloidosis, just as at casual detection Chronic renal insufficiency at usual (or even enlarged) the dimensions of nephroses and the expressed proteinuria. The probability of an amyloidosis is enlarged, if is available gepato - and a splenomegaly.

Authentic method of diagnostics of an amyloidosis is the nephros biopsy. Often enough an amyloid find and at a biopsy of a rectum, a liver, a gum. At the isolated lesion of heart the diagnosis can be put at an endomyocardial biopsy.

Treatment. At a secondary amyloidosis it is referred on basic disease treatment - application of antibiotics or operative treatment at chronic suppurative processes, an oncotomy, etc. Besides, there are the agents, inhibiting amyloidosis development. With definiteness it is possible to speak about positive influence on flow of disease of perennial reception on 100 - 150 gramme of a crude liver daily. At early stages of an amyloidosis of nephroses probably use of preparations 4-Aminoquinoline a number and Unithiolum. There are data on inhibiting influence on development of an amyloidosis of a colchicine which is especially effective at periodic illness. Use also a dimethylsulfoxide.

The question on action not all authors dares at flow of an amyloidosis of glucocorticoids and cytostatics unequivocally, however it is necessary to consider presence of an amyloidosis and nephrotic syndrome especially caused by it more likely as contraindication for such therapy. It is necessary to notice possibility of use of preparations (for example, Melphalanum), some clones of the lymphocytes in particular synthesising light chains of immunoglobulins oppressing function, participating in formation of an amyloid fibril that concerns first of all a primary amyloidosis and an amyloidosis at a multiple myeloma (АL-amyloid).

In the presence of Chronic renal insufficiency, an arterial hypertensia, a sprue, a heart failure spend also symptomatic therapy. At an amyloidosis of nephroses at stage Chronic renal insufficiency application of a hemodialysis and nephros transplantation is possible.