Pathology of atherosclerosis

2021-01-28 12:00 AM

Stage two, plain plaque appears. Middle thick plaque with necrotic areas in a fibrous shell. Necrotic areas contain a lot of fatty acids and cholesterol

Outline

 The World Health Organization defines: “Atherosclerosis is a combination of changes in the endothelial structure of the large and medium arteries, including local accumulation of lipids, glucides complexes., blood and blood products, fibrous tissue and acid deposits, these phenomena with alterations in the middle layer.

In general, atherosclerosis is a fibrosis of the artery wall consisting of the medium and large arteries. The main manifestation is the deposition of fat and cell membranes in the inner lining of the artery wall called plaque.

Atherosclerosis has been discovered in the Egyptian conventions from 50 years BC. Atherosclerosis causes 2 dangerous complications: myocardial infarction and stroke. In industrialized countries, 50% of deaths are due to cardiovascular disease, of which atherosclerosis accounts for 50%. In the United States, there are 88% of atherosclerosis in the US, in the elderly, no one does not have atherosclerosis. The disease is still found in young people, however. More than 300 American soldiers, on average, 22 years old, died in the Korean war, with an autopsy showing that 77% had atherosclerosis with a degree of more or less. In our country, there is no data on the entire population.

Causes and mechanisms of pathogenesis

Mechanism of pathogenesis

Recalling the artery structure:

The arterial wall is composed of 3 concentric layers from inside to outside as follows:

The inner layer or the endothelium: There is only a single layer made up of endothelial cells in the cell less low space and separated from the mesentery by the inner elastic layer.

The middle layer or the mesenchymal layer is made up of smooth muscle cells, collagen and elastin fibres, bounded by the outer layer of elasticity.

The outer layer of the outer layer or the outer lining is the connective tissue layer that feeds the blood vessels.

The process of developing atherosclerosis

Atherosclerosis is caused by thickening of artery walls consisting of a network of fibrous tissue surrounded by a layer of fat originating from the lower endothelium of the inner sac. Atherosclerotic atherosclerosis occurs mainly in the major arteries (abdominal, coronary, pelvic, carotid and descending), especially in the vortex regions such as bends or splits.

Atherosclerosis emerged years later with mechanisms that are gradually becoming better known today:

The first phase due to local hemodynamic disorder (vortex phenomenon) changes the normal structure of the inner layer. Lesions to appear earliest are fat-free edema, later appear fat-eating cells in the form of granular cells, clustered under the endothelial cells. At this stage, the vessel wall is disturbed, facilitating lipid deposition. This is followed by the formation of fat streaks on the endothelial surface.

Stage two, plain plaque appears. Middle thick plaque with necrotic areas in a fibrous shell. Necrotic areas contain a lot of fatty acids and cholesterol. The plaque progresses very quickly, causing the artery to narrow.

The final stage is the transformation into plaque-causing complications clogging the artery aperture and ischemic stroke. The main phenomenon of this development is the ulcer of the inner lining, which means the endothelium is torn, blood will flow in through the ulcer creating a blood clot. The tear of the endothelium causes the stickiness of the platelets, the origin of the embolism, and forms a clot, a blockage that covers the ulcer. This is the beginning of the complications later on. The plaques grow more and more, the calcium plaques stick together, the more plaque develops, causing the arteries to clog.

The hypothesis of atherosclerosis

There are many theories mentioned but not completely clear.

Arterial wall injury response hypothesis: The endothelium suffers from various damage such as chronic high cholesterol or injury, drugs, bacteria, allergic immunity, autoimmune. When the endothelium is damaged, it causes the single cell to attach to the endothelium, move through the endothelium and turn into macrophages. The macrophages are capable of capturing lipid particles, specially modified LDL. The presence of macrophages increases endothelial damage.

Cell Hypothesis: The infiltration of the artery wall of mononuclear leukocytes loses the ability of phagocytosis to damage or stimulate the growth of smooth muscle cells, macrophages, connective organizations, development of lesions the injury thereby causes atherosclerosis as stated in the injury theory.

Mitochondrial hypothesis: The mitochondrial enzymes in the vascular wall that can cause fat degeneration and accumulation in smooth muscle cells are the cholesterol ester hydrolase enzyme.

Monoclonal Theory: At the endothelial injury, the isozyme produces forms that stimulate the development of smooth muscle cells of the vascular wall like benign tumours, followed by atheroma.

The hypothesis of hyperlipidemia: This is the most widely accepted hypothesis because:

May cause atherosclerosis in the arterial test with a diet high in fat and cholesterol.

People with high blood lipid levels are more likely to have atherosclerosis than normal people, the structural component of atherosclerotic membranes is mainly lipid.

In addition, many authors also present new hypotheses about atherogenic mechanism related to the role of infection such as Helicobacter pylori, Chlamydia pneumonia, Cytomegalovirus.

Risk factors for atherosclerosis

Hyperlipidemia: Most epidemiological studies confirm that hypercholesterolemia is a major risk of atherosclerosis and a cause of anaemia. The risk, however, depends on the type of cholesterol-carrying lipoprotein. LDL Cholesterol plays an important role in atherosclerosis. It can be said that any increase in LDL cholesterol levels in the blood is at risk of causing atherosclerosis. Lipoprotein (a) or Lp (a) is also a high-risk factor in excess of 0.3 g / l.

Chylomicron appears to be of little significance in causing atherosclerosis partly because it is present both under physiological conditions, in part, it is rare to see an increase in atherosclerosis in parallel with an increase in chylomicrons.

HDL Cholesterol in contrast is a high anti-atherosclerotic factor because they transport cholesterol back to the liver in the condition where the artery wall has excess cholesterol, so it is also known as the good cholesterol.

 

Other risk factors:

THA: The YTNC is very high, especially for the brain blood vessels. High HA increases smooth muscle cell proliferation, thickens arterial mesothelium and increases elastin, colloid and glycosaminoglycans. The pressure exerted by high HA also easily ruptures atheroma as well as increases the endothelial permeability of cholesterol.

Smoking: also, the main risk factor, the risk of coronary artery doubles in smokers, especially those who smoke 40 cigarettes/day.

Diabetes: is the cause of lipid disorders, so it is easy to cause atherosclerosis.

Obesity, lack of activity.

Stress.

Birth control pills.

Classification of lesions according to the pathophysiology

According to artery damage

Grade I: Endothelial dysfunction. This damage is associated with high cholesterol and risk factors.

Grade 2: Endothelium. Associated with dyslipidemia, tobacco, diabetes.

Grade 3: Affects the whole central, fibrous plaque can progress heavily causing cracking. Associated with dyslipidemia, high blood pressure and genetics.

According to Stary's atherosclerosis progression

Stary 1: Only macrophages contain many lipid particles.

Stary 2: Fat strip appears.

Stary 3: Lipids appear outside the endothelial cells.

Stary 4: Deposition of many extracellular lipids.

Stary 5: T flavour atherosclerosis. Smooth muscle cells move and proliferate in the membrane.

Stary 6: Lesions with blood clots or bleeding.

Stary 7: T flavour calcification. Calcium deposition replaces calcified lipids and cell debris.

Stary 8: Some lesion sites are replaced by colloid to form fibrosis lesions.

Symptom

Clinical symptom progression usually goes through 3 stages:

Potential stage: No clinical manifestations

Clinical stage: There are typical symptoms of organ anaemia

Complicated stage organs caused by ischemia. Symptoms usually depend on the organs damaged.

Aortic atherosclerosis

Commonly seen in order is the aortic root, the thoracic aorta, the abdominal aorta is the place where the pelvic artery is divided.

Angina if there is coronary atherosclerosis.

If damage to aorta: clinical symptoms are symptoms of aortic valve stenosis or aortic stenosis or a combination.

Aortic dissection: if severe with angina state, it is easy to confuse myocardial infarction but does not respond to coronary vasodilators except for Morphine.

Abdominal atherosclerosis

The first stage is mild, only gastrointestinal disturbances, then abdominal pain at night, after meals.

Severe or severe stenosis: may cause bleeding or perforation of the stomach, gangrene of the mesenteric lining, intestines.

An examination can detect dilated aorta and severe complications in rupture causing abdominal bleeding, death.

Diagnosis requires a combination of ultrasound, Doppler ultrasound and especially aortic scan

stomach.

Cerebral atherosclerosis

Early manifestation is the state of anaemia with sagging, tinnitus, memory disorders, forgetfulness; later confusion, unable to concentrate, insomnia. Serious complications are cerebral embolism causing paralysis, speech disorder, consciousness disorder or, worse, coma.

Coronary atherosclerosis

With manifestations of chronic or acute coronary failure such as myocardial infarction

Renal atherosclerosis

Chronic kidney anaemia causes fibrosis, hypertension due to narrow renal artery. Confirming the diagnosis should be based on urine tests, ultrasound, kidney angiography or kidney biopsy.

Atherosclerosis of the lower extremities

Damage to most arteries except the instep artery is less common. Symptoms of anemia are common with cold legs, pain intermittent, BP difference or failure to capture the embolism side. Complications can later cause necrosis. Diagnosis should be based on Doppler ultrasound, angiography.

Classification of atherosclerosis according to Fontaine has 4 stages:

Stage 1: No clinical symptoms

Stage 2: There are two levels of pain:

2a: Walking diameter of over 100m.

2b: Walking diameter is less than 100m.

Stage 3: Intermittent pain that occurs at rest.

Stage 4: Necrosis of the extremities.

Atherosclerosis elsewhere

Temporal artery: Causes headaches such as Horton or Migraine disease.

Basal artery: Causes visual disturbances

Mach action to lower pituitary cerebral suture: Causes diabetes insipidus

Pancreatic artery: Causes diabetes

Diagnose

Diagnosis is based on many controls and the results of the subclinical survey do not have a clear standard. May:

Functional disorders caused by organ or peripheral ischemia.

Presence of risk factors.

Peripheral artery condition.

Test results: fundoscopy, bilan lipid test, contrast angiography, doppler ultrasound.

Treatment

The principles of treatment

There are 3 main purposes

Treat the main risk factors: lipid disorders, diabetes mellitus, hypertension, and tobacco use before symptoms (primary prevention) or symptoms (secondary prevention).

Treatment of primary and secondary atherosclerosis complications (anti-platelet agglutination treatment)

Specific treatment of lesions: Some risks of parallel combination need treatment such as: hormone replacement therapy in perimenopause, diet in obesity, increased physical activity

Specific treatment

Change in risk factors (YTNC):

Some of the YTNCs of atherosclerosis can work to prevent the progression or gradually reduce atherosclerosis: Stop smoking, control BP, stabilize blood sugar, avoid alcohol too much, exercise regularly. control of dyslipidemia is the most frequent. Many studies have shown that treatment has the ability to significantly reduce cardiovascular complications, but has little effect on minimizing atherosclerosis.

ACE inhibitors and beta-blockers:

Many studies show that these two drugs can reduce the risk of heart attack and ischemic heart disease in general. For example, ACE inhibitors decreased by 14 to 28% of cardiovascular events; Beta-blockers reduce mortality after myocardial infarction by 20%, infarction recurrence by 25% and sudden death by 30%.

Treatment of hyperlipidemia:

Treatment of atherosclerosis is a comprehensive treatment that includes a variety of internal and surgical measures, but one of the primary goals is still a regression of atherosclerosis with lipid deposition, a reduction in lipoprotein components. harmful blood.

Classification of hyperlipidemia according to Frederickson. Is the most common classification, classics. There are 5 possible:

Type 1: Increase mainly chylomicron, billion TG / CT> 2.5.

Type 2: Divided into 2 bodies: type IIa: increase LDL-C with billion TC / TG> 2.5 and type IIb: increase both LDL-C and HDL-C, billion TG / TC or TC / TG ​​<2.5.

Type 3: Uncommon, increase IDL-C, billion TG / TC <2.5.

Type 4: Increase VLDL-C, billion TG / TC> 2.5

Type 5: Rarely, increased both chylomicron and VLDL-C.

In the upper body to be treated are IIa, IIb and IV due to the high risk of atherosclerosis.

Lipid-lowering drugs

Consists of 4 main groups:

Group 1: are substances that capture bile salts. The main effect is to reduce LDL-C. These are ion exchange resins that bind to bile salts in the small intestine disrupting the circulation of bile salts in the hepatobiliary cycle and stimulate the conversion of cholesterol to bile salts in the liver. This stimulates the formation of LDL receptors thereby reducing serum LDL. Leading the group is cholestyramine (Questran), reducing cholesterol 15-30% and triglycerides from 5-15% with a dose of 4-16 g / day. Colestipol dose 5-20 g / day. Side effects: constipation, bloating, nausea.

Group 2: Fibrates have the effect of increasing lipoprotein lipase activity, increasing the degeneration of VLDL-C and IDL-C, thereby reducing triglycerides. The advantage is that HDL -C increases with the use of fibrate. Side effects include digestive disorders, increased gallstones. Common drugs like fenofibrate (Lipanthyl) reduce CT (15-30%) and TG (15-30%), dose from 100-300mg / day. Gemfibrozil 600 mgx 2 times / day or Clofibrate 500mg x 2-3 times / day.

Group 3: Having nicotinic acid and derivatives. Effective when using high doses. Effectively reduces the formation of VLDL in the liver thereby reducing HDL. Nicotinic acid reduces CT (5-15%) and TG (15-30%) and increases both HDL-C. A common drug is probucol (Lurselle) dose of 0.3-0.6g / day. Side effects: flushing, hyperglycemia, hyperuricemia, digestive disorders, liver toxicity. Need to monitor liver function during treatment. Facial flushing can be controlled with aspirin.

Group 4: L are statins, reduce CT> 30-50% and TG 15-50%. This is a group of drugs that have a strong effect on lowering blood cholesterol. The mechanism of action is inhibition of the enzyme HMG CoE reductase, which inhibits the metabolism of intracellular cholesterol. Inhibition of this process will increase LDL receptor synthesis, thereby lowering serum cholesterol. Common drugs are Fluvastatin 20-40mg / day, Lovastatin 10-80mg / day, Pravastatin 10-40mg / day, Simvastatin 5-40mg / day. Side effects include indigestion, constipation, abdominal pain, cramps, and possibly liver toxicity, so liver enzymes should be monitored.

The choice of drugs

It should be based on an increase in lipid composition primarily.

If CT increases: The priority is the resins, the statins, and the fibrates or nicotinic acid. Can combine resin with statin or resin with nicotinic acid

If TG is increased: The priority is fibrates and then nicotinic acid. Can combine fibrate and resin or nicotinic acid and resin

If both CT and TG increase: Priority is fibrate then stanine, nicotinic acid. Resin can be combined with nicotinic acid or fibrate with resin or resin with statin.

The treatment of hyperlipidemia usually takes many months and years and the high cost of side effects should be considered. In addition to treating risk factors, it is very important to use the drug to reach the standard level such as CT must be reduced below 200mg% and or the TG is below 200mg%.

Antioxidants

As vitamins A, C, E, fish liver oil.

Vasodilators:

Papaverine 0.04g X 2-4 tablets / day, Hydergine 3-6mg / day, Tegretol 100mgX 3-6 tablets / day. There are also many similar preparations that can be applied Vastarel, Fonzylane, Praxilene, Torrential, Sermion, Trivastal, Cervoxan.

Surgical treatment

Surgical removal of a blockage or balloon artery angioplasty with stent placement, a bridge over the shortcut.

Prevent blood clots

A blood clot forms on the atherosclerotic plaque causing rapid disease progression and complications such as coronary artery disease. Aspirin is effective in preventing recurrence of acute MI, 100 mg/day alone or in combination with dipyridamole (Persantine) 75-150 mg/day.

Preventive

Divide into 2 levels of redundancy, primary and secondary.

Primary prophylaxis:

For early prophylaxis even at birth:

Ensure a breast milk diet, avoid foods that increase lipids such as sugars and starches.

Reduce salt in your diet to reduce high blood pressure. Ensure a diet rich in fruits and vegetables, and eat plenty of fresh fish. No smoking.

There is an exercise regime to prevent obesity. Exercise according to the level of exercise has anti-increased lipoprotein ​​harmful effects.

Birth planning to avoid gaining weight after giving birth.

Secondary backup:

For patients with atherosclerosis complications.

Actively treat the causes or risk factors for disease such as tobacco, diabetes, high blood pressure. Reduce stress, increase physical activity.

Monitor and treat complications at regular monitoring centres to avoid relapses.