Mikroangiopatija

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Mikroangiopatija

Defined as damage to small blood vessels, microangiopathy is observed in various pathologies. It can induce suffering in different organs, with very variable consequences depending on whether it is associated with diabetes (diabetic microangiopathy) or with a thrombotic microangiopathy syndrome. Organ failures (blindness, renal failure, multiple organ damage, etc.) are observed in the most serious cases and in the event of delay or failure of treatment.

What is microangiopathy?

definicija

Microangiopathy is defined as damage to small blood vessels, and more particularly arterioles and arteriolar capillaries that supply organs. It can occur under different conditions:

  • Diabetic microangiopathy is a complication of type 1 or 2 diabetes. The damage to the vessels is usually located in the eye (retinopathy), kidney (nephropathy) or nerve (neuropathy). It can thus cause vision damage up to blindness, kidney failure, or even nerve damage.
  • Thrombotic microangiopathy is a component of a group of diseases in which small vessels are blocked by blood clots (formation of aggregates of blood platelets). It manifests itself in various syndromes associating blood abnormalities (low levels of platelets and red blood cells) and failure of one or more organs such as the kidney, brain, intestines or heart. The most classic forms are thrombotic thrombocytopenic purpura, or Moschowitz syndrome, and hemolytic uremic syndrome. 

uzroci

Dijabetička mikroangiopatija

Diabetic microangiopathy results from chronic hyperglycemia which causes damage to the vessels. These lesions set in late, with the diagnosis often being made after 10 to 20 years of disease progression. They are all the more early when the blood sugar is poorly controlled by drugs (glycated hemoglobin, or HbA1c, too high).

In diabetic retinopathy, excess glucose first leads to localized micro-occlusions of the vessels. Small dilations of the vessels are then created upstream (microaneurysms), leading to small hemorrhages (punctiform retinal hemorrhages). This damage to the blood vessels results in the appearance of poorly irrigated retinal areas, called ischemic areas. At the next stage, new abnormal vessels (neovessels) proliferate on the surface of the retina in an anarchic fashion. In severe forms, this proliferative retinopathy causes blindness.

In diabetic nephropathy, microangiopathy causes lesions in the vessels supplying the glomeruli of the kidney, structures dedicated to filtering blood. Weakened vessel walls and poor irrigation ultimately impair kidney function.

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In diabetic neuropathy, damage to the nerves results from microangiopathy, combined with direct damage to nerve fibers due to excess sugar. They can affect peripheral nerves, which control muscles and transmit sensations, or nerves in the autonomic nervous system that control the functioning of the viscera.

Microangiopathie thrombotique

The term thrombotic microangiopathy designates diseases with very different mechanisms despite their common points, the causes of which are not always known.

Thrombotic Thrombocytopenic Purpura (TTP) most often has an autoimmune origin. The body makes antibodies that block the function of an enzyme called ADAMTS13, which normally prevents the aggregation of platelets in the blood. 

In rarer cases, there is a permanent deficiency of ADAMTS13 linked to hereditary mutations.

The hemolytic uremic syndrome (HUS) results in the vast majority of cases from an infection. The different bacterial strains incriminated secrete a toxin called shigatoxin, which attacks the vessels. But there are also hereditary HUS, linked to cancer, to an HIV infection, to a bone marrow transplant or to the taking of certain drugs, in particular anti-cancer drugs.

dijagnostički

The diagnosis of microangiopathy is primarily based on clinical examination. The doctor may perform various examinations depending on the context of occurrence and the symptoms, for example:

  • fundus or angiography to detect and monitor diabetic retinopathy,
  • determination of micro-albumin in the urine; testing for creatinine in the blood or urine to monitor kidney function,
  • blood count to check for low levels of platelets and red blood cells in the blood,
  • search for infections,
  • imaging (MRI) for brain damage

Zabrinuti ljudi

Diabetic microangiopathies are relatively common. About 30 to 40% of diabetics have retinopathy at different stages, or about a million people in France. It is the leading cause of blindness before the age of 50 in industrialized countries. Diabetes is also the leading cause of end stage renal disease in Europe (12 to 30%), and an increasing number of type 2 diabetics require dialysis treatment.

Thrombotic microangiopathies are much less common:

 
  • The frequency of PPT is estimated at 5 to 10 new cases per million inhabitants per year, with a female predominance (3 women affected for 2 men). Hereditary PTT, which is observed in children and newborns, is a very rare form of thrombotic microangiopathy, with only a few dozen cases identified in France.
  • The frequency of SHUs is of the same order as that of PPT. Children are the main targets of the infections that are responsible for them in France, HUS in adults being more often due to infections contracted during travel (in particular by the agent of dysentria).
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Faktori rizika

The risk of diabetic microangiopathy may be increased by genetic factors. Arterial hypertension, and more generally cardiovascular risk factors (overweight, increased blood lipid levels, smoking), can be aggravating factors.

PPT can be promoted by pregnancy.

Symptoms of microangiopathy

Dijabetička mikroangiopatija

Symptoms of diabetic microangiopathy set in insidiously. The evolution is silent until the appearance of complications:

 
  • vision disturbances linked to retinopathy,
  • fatigue, urinary problems, high blood pressure, weight loss, sleep disturbances, cramps, itching, etc. in case of renal failure,
  • pain, numbness, weakness, burning or tingling sensations for peripheral neuropathies; diabetic foot: infection, ulceration or destruction of the deep tissues of the foot with a high risk of amputation; sexual problems, digestive, urinary or cardiac disorders when neuropathy affects the autonomic nervous system …

Microangiopathie thrombotique

The symptoms are varied, and most often onset.

The collapse of the level of blood platelets (thrombocytopenia) in the PTT causes bleeding, which is expressed by the appearance of red spots (purpura) on the skin.

Anemia associated with low red blood cell count can manifest as severe fatigue and shortness of breath.

 

Organ pain varies widely but is often significant. In severe cases, there may immediately be a drop in vision, impairments in the limbs, neurological (confusion, coma, etc.), cardiac or digestive disorders, etc. Kidney involvement is generally moderate in PTT, but can be severe in HUS. The bacteria responsible for HUS are also the cause of sometimes bloody diarrhea.

Treatments for microangiopathy

Treatment of diabetic microangiopathy

Diabetes medical treatment

The medical treatment of diabetes makes it possible to delay the onset of microangiopathy and to limit the consequences of damage to the vessels. It is based on hygienic and dietary measures (appropriate diet, physical activity, weight loss, avoidance of tobacco, etc.), on monitoring the blood sugar level and on the establishment of an appropriate drug treatment (anti-diabetic drugs or insulin).

Management of diabetic retinopathies

The ophthalmologist may suggest laser photocoagulation treatment targeting the early lesions of the retina to prevent them from progressing.

At a more advanced stage, pan-retinal photocoagulation (PPR) should be considered. The laser treatment then concerns the entire retina, except the macula responsible for central vision.

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In severe forms, surgical treatment is sometimes necessary.

Management of diabetic nephropathies

At the stage of end-stage renal disease, it is necessary to compensate for the dysfunction of the kidneys either by dialysis or by resorting to a renal transplant (transplant).

Management of diabetic neuropathies

Different classes of drugs (antiepileptics, anticonvulsants, tricyclic antidepressants, opioid analgesics) can be used to combat neuropathic pain. Symptomatic treatments will be offered in the event of nausea or vomiting, transit disorders, bladder problems, etc.

Microangiopathie thrombotique

Thrombotic microangiopathy often justifies the establishment of emergency treatment in an intensive care unit. For a long time, the prognosis was rather bleak because there was no suitable treatment and the diagnosis was inefficient. But advances have been made and now allow healing in many cases.

Medical treatment of thrombotic microangiopathy

It is mainly based on plasma exchanges: a machine is used to replace the patient’s plasma with plasma from a voluntary donor. This treatment makes it possible to supply the ADAMTS13 protein which is deficient in the PTT, but also to rid the patient’s blood of autoantibodies (HUS of autoimmune origin) and of proteins which promote the formation of clots.

In children suffering from HUS associated with a shigatoxin, the outcome is often favorable without the need for plasma exchange. In other cases, plasma exchanges should be repeated until the platelet count is normalized. They are rather effective, but can present risks of complications: infections, thromboses, allergic reactions …

They are often associated with other treatments: corticosteroids, antiplatelet drugs, monoclonal antibodies, etc.

Treatment of infections with antibiotics should be individualized.

Management of associated symptoms 

Resuscitation measures may be necessary during emergency hospitalization. The occurrence of neurological or cardiological symptoms is closely monitored.

In the long term, sequelae such as renal failure are sometimes observed, justifying therapeutic management.

Prevent microangiopathy

The normalization of blood sugar and the fight against risk factors is the only prevention of diabetic microangiopathies. It should be combined with regular monitoring of the eyes and kidney function.

Antihypertensive drugs have a protective effect on the kidney. It is also advisable to reduce the intake of dietary protein. Certain drugs that are toxic to the kidney should be avoided.

Prevention of thrombotic microangiopathies is not possible, but regular monitoring may be necessary to avoid relapses, especially in people with TTP.

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