Disorders of protein metabolism

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I- GENERAL :

Protein metabolism plays an essential role in the functioning of cells and tissues .The proteins are made within the ribosome from amino acids supplied by food. These proteins are then excreted in the extracellular medium or accumulated in the endoplasmic reticulum. The Golgi apparatus plays a role in the storage, coupling or excretion of these proteins. Protein molecules are either used, be excreted at a rate which varies from one organ to another. A dynamic balance is normally established between the rate of synthesis and protein use. But many pathological conditions can disturb this balance at different levels :

■ Cell : Inhibition of synthesis due tetrachloride. Disturbance of the excretion with abnormal accumulation of proteins in the endoplasmic reticulum which expands causing cell degeneration or cell death.

■ Intercellular : Pathological protein deposits. These deposits realize 3 specific changes of the intercellular environment : L’amylose, the fibrinoid and hyaline.

II- AMYLOSE :

Also called amyloid or amyloid disease, amyloid is a pathological deposit of a homogeneous substance of ivory white color on a fresh member is colored brown by iodine as starch. The term amyloidosis is inappropriate, it is related to its coloration with iodine. Indeed, it is not a carbohydrate poly substance, but a glucoproteique substance with a protein component is greater but its carbohydrate component gives him the analogy with the starch.

1- IN MACROSCOPIE :

Amyloidosis is demonstrated by the reaction MECKEL. It involves applying iodine (lugol) on the cut surface of the fees affected organ : gives A SHADE BROWN MAHOGANY THAT TURNS BLUE-VIOLET, after application of a sulfurized acid solution 10%.

It is situated at the start in the glandular epithelium and endothelium in arterioles, then extends into the intercellular space and the entire thickness of the vascular walls, causing atrophy and loss of tissue.

2- IN OPTICAL MICROSCOPY :

After routine hematoxylin eosin staining, amylose if the color vanes en rose. Other elective colorings are used to highlight amyloidosis :
– RED CONGO : colors it red currant. In light polarized birefringence of amyloid is obtained.
– THE VIOLET Methyl : red purple and performs Metachromasia
– GREEN METHYL : violet coloration.
– LA THIOFLAVINE T : a pale green fluorescence microscopic examination under ultraviolet light.

3- ELECTRONIC MICROSCOPY :

It appears fibrillar structure. It consists of fibrils 7,5 – 10 nm which have jumble.

4- BIOCHEMICAL STRUCTURE :

The amyloid comprises :
– A carbohydrate moiety : 10-15% about.
– A protein fraction, basic, fibrillar structure made of protein fragments related to immunoglobulins. These fibrils are of several types according to their etiologies. Indeed, no one but the amyloids.

5- VARIETY CLINICAL ANATOMY :

A – AMYLOIDOSIS systematized OR WIDESPREAD :

  • PRIMITIVE GENERALIZED AMYLOSIS : (par perturbation immunocytaire). It includes all forms of amyloidosis in which the biochemical structure of amyloid fibrils is composed of light polypeptide chains kappa or lambda immunoglobulin, they say he is AL amyloid. This is the case of amyloid in the plasma cell dyscrasias : multiple myeloma, Disease Waldenstrôme. In this variety the amyloid preferentially localizes in skeletal muscle streak (language), digestive tract, larynx and lung.
  • AMYLOSE WIDESPREAD SECONDARY : This is the most common, is characterized by achieving major hepato-renal-spleno .It is associated with a chronic disease process such as :

– Inflammation granulomateuse (tuberculosis etc.).
– chronic suppurations : chronic osteomyelitis, bronchiectasis suppurative.
– chronic rheumatic inflammation.
– Cancers (rein, stomach, Hodgkin's disease etc.).

In this form, the biochemical composition of the fibrils is different from the previous : Amyloid is called A or AA amyloid.

  • MORPHOLOGICAL ASPECTS :

– LIVER : He rose very firm volume. Its surface is smooth, the cut surface is shiny. Histologiquement, deposits sit between the sinusoid and liver span. The compressed liver cells and whose exchanges are disrupted eventually fade.
– LA RATE : rarely huge, hard or elastic consistency. It has sometimes translucent deposits nodularisés, scattered in the white pulp sometimes a massive infiltration of the red pulp.
– THE KIDNEY : He's fat, blade, closed, cortical shows a yellowish tint. Histologically achieving interested glomerulus.

B- AMYLOIDOSIS LOCALIZED :

very rare form.
Examples :

  • cutaneous lichen amyloidosis or amyloid.
  • Amylose du tract gastro-intestinal.
  • senile amyloidosis (heart, lung, brain : Alzheimer's Disease)
  • Stroma amyloid certain tumors : Medullary thyroid carcinoma.

6- CONSEQUENCES OF Amylose :

The increased volume of deposits and their significance gradually lead to compression and smothering of nearby structures whether or not epithelial. The final stage is the atrophy of the affected organs or leading to impaired function of the affected organ. Reversibility is controversial.

7- OF STUDY :

The biopsy for histological study is an appropriate means for the diagnosis of clinically suspected amyloidosis. The choice of biopsy depends on the clinical and etiological context.

In biopsy secondary generalized amyloidosis puncture the kidney and especially of the liver is indicated. In primitive generalized amyloidosis, or in localized amyloidoses, rectal biopsy or gum is a means of choice and allows diagnosis in 75% of cases.

8- PATHOGENESIS amyloidosis :

Currently amyloidosis are considered to be related to disturbances of innate immune reactions or acquired :

  • In humans, amyloid deposits coincide with either a quantitative disorder (hypo or hyperactivity) with either a qualitative immune system disorder. However, neither the pathogenic mechanism or the cells that produce amyloid fibrils are not currently known with certainty.
  • In animals, it is shown an induction phase dependent T cells that accumulate before and diminish the appearance of the deposit from the moment or amyloidosis settles. Electron microscope, This abnormal protein and its precursor are manufactured by reticulo-histiocytic cell, monocytes, macrophages, histiocytes.

III- OTHER DEPOSITS CONDITIONS :

1- LA SUBSTANCE HYALINE :

It refers to a substance having an aspect FROSTED GLASS macroscopically, and corresponds histologically to anhistes deposits, homogeneous, eosinophils. On distingue :

  • vascular hyaline : interested especially small vessels (ex : Diabetes, lupus erythematosus, HTA benign.
  • hyaline conjunctiva : it is thick and dense collagen which takes a look says hyaline (ex : scar secondary to an inflammatory process, Multiple senile uterus and annexes after menopause).

His demonstrated by optical microscopy based on the same staining of collagen.

It does not take the PAS.

2- LA SUBSTANCE FIBRINOIDE :

It refers to an amorphous structure, eosinophilic, uniform which as its name suggests, has certain morphological characteristics of fibrin. Elle offers an aspect finement filamenteux or nucleus and color in roses take the Eosine, It is NOT positive.

It is observed in various circumstances :

  • In the normal state it is found in the placenta.
  • In the pathological condition is found :

– In the wall of the renal vessels in diabetes,
– In rheumatoid arthritis, in synovial and skin nodules juxtaarticular.
– In some allergic acute inflammations.

Course of Dr N. lemma – Faculty of Constantine