Peptic Ulcer Disease

Peptic ulcer  :

It is a chronic inflammatory condition involving a group of disorders characterised by ulceration in regions of upper gastrointestinal tract where parietal cells secrete pepsin and hydrochloric acid.

Ulcer is defined as the erosion in the lining of the stomach or duodenum and is caused by the disruptions of the gastric mucosal defense and repair systems. Ulcer in the stomach is called gastric ulcer and in the duodenum is called duodenal ulcer and together peptic ulcer. In clinical practice, peptic ulcer is one of the most prevalent gastrointestinal disorders, commonly occurs in developed countries.Peptic ulcer, also known as PUD or peptic ulcer disease is a break in the lining (mucosa) of the digestive tract produced by digestion of the mucosa by pepsin and acid.

An estimated 15,000 deaths occur each year as a consequence of PUD. In India PUD is common. In Indian pharmaceutical industry, researchers reported that peptic ulcers were been caused by an imbalance between the aggressive factors and a number of known defense mechanisms. Exogenous aggressive factors such as smoke, anti-inflammatory drugs, alcohol, stress, fatty foods and Helicobacter pylori infections triggered tissue necrosis through mucosal ischemia, free radical generation and cessation of nutrient delivery, hydrochloric acid together with pepsin, pancreatic enzymes and bile decreased the defense mechanisms of gastrointestinal mucosa such as the intercellular junctions, local blood flow, mucus/bicarbonate secretion and cellular. Antacids, and antiulcer drugs share 6.2 billion rupees and occupy 4.3% of the market share.

 

Causes of atherosclerosis

Some researchers believe that atherosclerosis may be caused by an
 Infection of the vascular smooth muscle cells; chickens, for example, develop atherosclerosis when infected with the Marek's disease herpesvirus. Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation. Cholesteryl ester accumulation is associated with atherosclerosis.

Also, cytomegalovirus (CMV) infection is associated with cardiovascular diseases.
Linus Pauling's and Matthias Rath's extended theory states that deaths from scurvy in humans during the ice age, when vitamin C (an antioxidant) was scarce, selected for individuals who could repair arteries with a layer of cholesterol provided by lipoprotein(a), a lipoprotein found in vitamin C-deficient species (higher primates and guinea pigs). Pauling and Rath theorised that, although eventually harmful, lipoprotein deposition on artery walls was beneficial to the human species and a "surrogate for ascorbate" in that it kept individuals alive until access to vitamin C allowed arterial damage to be repaired. Atherosclerosis is thus a vitamin-C-deficiency disease.

Diagnosis of atherosclerosis

Over the last couple of decades, methods other than angiography and stress-testing have been increasingly developed as ways to better detect atherosclerotic disease before it becomes symptomatic. These have included both (a) anatomic detection methods and (b) physiologic measurement methods.
Examples of anatomic methods include: (1) coronary calcium scoring by CT, (2) carotid IMT (intimal media thickness) measurement by ultrasound, and (3) intravascular ultrasound (IVUS).
Examples of physiologic methods include: (1) lipoprotein subclass analysis, (2) HbA1c, (3) hs-CRP, and (4) homocysteine.

The example of the metabolic syndrome combines both anatomic (abdominal girth) and physiologic (blood pressure, elevated blood glucose) methods.
Advantages of these two approaches: The anatomic methods directly measure some aspect of the actual atherosclerotic disease process itself, thus offer potential for earlier detection, including before symptoms start, disease staging and tracking of disease progression. The physiologic methods are often less expensive and safer and changing them for the better may slow disease progression, in some cases with marked improvement.

Disadvantages of these two approaches: The anatomic methods are generally more expensive and several are invasive, such as IVUS. The physiologic methods do not quantify the current state of the disease or directly track progression. For both, clinicians and third party payers have been slow to accept the usefulness of these newer approaches.

Diagnosis of Atherosclerosis

Diagnosis

Microphotography of arterial wall with calcified (violet colour) atherosclerotic plaque (haematoxillin & eosin stain)

Areas of severe narrowing, stenosis, detectable by angiography, and to a lesser extent "stress testing" have long been the focus of human diagnostic techniques for cardiovascular disease, in general. However, these methods focus on detecting only severe narrowing, not the underlying atherosclerosis disease. As demonstrated by human clinical studies, most severe events occur in locations with heavy plaque, yet little or no lumen narrowing present before debilitating events suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility and sometimes sudden death.
Plaques that have ruptured are called complicated plaques.

 The extracellular matrix of the lesion breaks, usually at the shoulder of the fibrous cap that separates the lesion from the arterial lumen, exposing thrombogenic material, mainly collagen, and eventually causing thrombus formation. This thrombus will eventually grow and travel downstream until eventually occluding a narrow artery. Once the area is blocked, blood and oxygen will not be able to supply the vessels and will cause death of cells and lead to necrosis and poisoning. Serious complicated plaques can cause death of organ tissues, causing serious complications to that organ system.

Greater than 75% lumen stenosis used to be considered by cardiologists as the hallmark of clinically significant disease because it is typically only at this severity of narrowing of the larger heart arteries that recurring episodes of angina and detectable abnormalities by stress testing methods are seen. However, clinical trials have shown that only about 14% of clinically debilitating events occur at locations with this, or greater severity of stenosis. The majority of events occur due to atheroma plaque rupture at areas without narrowing sufficient enough to produce any angina or stress test abnormalities. Thus, since the later-1990s, greater attention is being focused on the "vulnerable plaque.
Though any artery in the body can be involved, usually only severe narrowing or obstruction of some arteries, those that supply more critically important organs are recognized. Obstruction of arteries supplying the heart muscle result in a heart attack. Obstruction of arteries supplying the brain result in a stroke. These events are life-changing, and often result in irreversible loss of function because lost heart muscle and brain cells do not grow back to any significant extent, typically less than 2%.

Causes of Athersclerosis

Causes:

The main cause of atherosclerosis is yet unknown, but is hypothesized to fundamentally be initiated by
 Inflammatory processes in the cell wall in response to retained low-density lipoprotein (LDL) molecules . Once inside the vessel wall, LDL molecules become susceptible to oxidation by free radicals, and become toxic to the cells. The damage caused by the oxidized LDL molecules triggers a cascade of immune responses which over time can produce an atheroma. The LDL molecule is globular shaped with a hollow core to carry cholesterol throughout the body.

The body's immune system responds to the damage to the artery wall caused by oxidized LDL by sending specialized white blood cells (macrophages and T-lymphocytes) to absorb the oxidized-LDL forming specialized foam cells. These white blood cells are not able to process the oxidized-LDL, and ultimately grow then rupture, depositing a greater amount of oxidized cholesterol into the artery wall. This triggers more white blood cells, continuing the cycle.
Eventually, the artery becomes inflamed. The cholesterol plaque causes the muscle cells to enlarge and form a hard cover over the affected area. This hard cover is what causes a narrowing of the artery, reduces the blood flow and increases blood pressure.

Signs and symptoms of Atherosclerosis

Signs and symptoms

Atherosclerosis typically begins in early adolescence, and is usually found in most major arteries, yet is asymptomatic and not detected by most diagnostic methods during life. Atheroma in arm, or more often in leg arteries, which produces decreased blood flow is called peripheral artery occlusive disease  (PAOD).
According to United States data for the year 2004, for about 65% of men and 47% of women, the first symptom of atherosclerotic cardiovascular disease is heart attack or sudden cardiac death (death within one hour of onset of the symptom).

Most artery flow disrupting events occur at locations with less than 50% lumen narrowing (~20% stenosis is average). The illustration above, like most illustrations of arterial disease, overemphasizes lumen narrowing, as opposed to compensatory external diameter enlargement (at least within smaller arteries, e.g., heart arteries) typical of the atherosclerosis process as it progresses (see Glagov or the ASTEROID trial). The relative
geometry error within the illustration is common to many older illustrations, an error slowly being more commonly recognized within the last decade.
Cardiac stress testing, traditionally the most commonly performed non-invasive testing method for blood flow limitations, in general, detects only lumen narrowing of ~75% or greater, although some physicians claim that nuclear stress methods can detect as little as 50%.




 References:

    Text book of Clinical pharmacy and Therapeutics by Eric T. Herfindal. 

   Text book of Pathophysiology by Dr.S.L.Bodhankar.

Complications of Atherosclerosis

Complications of Atherosclerosis

These complications of advanced atherosclerosis are chronic, slowly progressive and cumulative. Most commonly, soft plaque suddenly ruptures (see vulnerable plaque), causing the formation of a thrombus that will rapidly slow or stop blood flow, leading to death of the tissues fed by the artery in approximately 5 minutes. This catastrophic event is called an infarction.

One of the most common recognized scenarios is called coronary thrombosis of a coronary artery, causing myocardial infarction (a heart attack). The same process in an artery to the brain is commonly called stroke. Another common scenario in very advanced disease is claudication from insufficient blood supply to the legs, typically caused by a combination of both stenosis and aneurysmal segments narrowed with clots.

Atherosclerosis can occur body-wide, in the arteries to the brain, intestines, kidneys, legs, etc. with many infarctions involving only very small amounts of tissue. These are termed "clinically silent" because the person having the infarction does not notice the problem and does not seek medical help, or when they do, physicians do not recognize what has happened.