№ 4. Diseases of the Cardiovascular System (Myocardial Infarction. Atherosclerosis).

Diseases of the Heart and Cardiovascular System

Cardiac muscle cells are serviced by a system of coronary arteries. During exercise the flow through these arteries is up to five times normal flow. Blocked flow in coronary arteries can result in death of heart muscle, leading to a heart attack.

Blockage of coronary arteries, shown in Figure 16, is usually the result of gradual buildup of lipids and cholesterol in the inner wall of the coronary artery. Occasional chest pain, angina pectoralis, can result during periods of stress or physical exertion. Angina indicates oxygen demands are greater than capacity to deliver it and that a heart attack may occur in the future. Heart muscle cells that die are not replaced since heart muscle cells do not divide. Heart disease and coronary artery disease are the leading causes of death in the United States.

Hypertension, high blood pressure (the silent killer), occurs when blood pressure is consistently above 140/90. Causes in most cases are unknown, although stress, obesity, high salt intake, and smoking can add to a genetic predisposition. Luckily, when diagnosed, the condition is usually treatable with medicines and diet/exercise.

The Vascular System

Two main routes for circulation are the pulmonary (to and from the lungs) and the systemic (to and from the body). Pulmonary arteries carry blood from the heart to the lungs. In the lungs gas exchange occurs. Pulmonary veins carry blood from lungs to heart. The aorta is the main artery of systemic circuit. The vena cavae are the main veins of the systemic circuit. Coronary arteries deliver oxygenated blood, food, etc. to the heart. Animals often have a portal system, which begins and ends in capillaries, such as between the digestive tract and the liver.

Fish pump blood from the heart to their gills, where gas exchange occurs, and then on to the rest of the body. Mammals pump blood to the lungs for gas exchange, then back to the heart for pumping out to the systemic circulation. Blood flows in only one direction.

Blood

Plasma is the liquid component of the blood. Mammalian blood consists of a liquid (plasma) and a number of cellular and cell fragment components as shown in Figure 21. Plasma is about 60 % of a volume of blood; cells and fragments are 40%. Plasma has 90% water and 10% dissolved materials including proteins, glucose, ions, hormones, and gases. It acts as a buffer, maintaining pH near 7.4. Plasma contains nutrients, wastes, salts, proteins, etc. Proteins in the blood aid in transport of large molecules such as cholesterol.

Red blood cells, also known as erythrocytes, are flattened, doubly concave cells about 7 µm in diameter that carry oxygen associated in the cell’s hemoglobin. Mature erythrocytes lack a nucleus. They are small, 4 to 6 million cells per cubic millimeter of blood, and have 200 million hemoglobin molecules per cell. Humans have a total of 25 trillion red blood cells (about 1/3 of all the cells in the body). Red blood cells are continuously manufactured in red marrow of long bones, ribs, skull, and vertebrae. Life-span of an erythrocyte is only 120 days, after which they are destroyed in liver and spleen. Iron from hemoglobin is recovered and reused by red marrow. The liver degrades the heme units and secretes them as pigment in the bile, responsible for the color of feces. Each second two million red blood cells are produced to replace those thus taken out of circulation.

White blood cells, also known as leukocytes, are larger than erythrocytes, have a nucleus, and lack hemoglobin. They function in the cellular immune response. White blood cells (leukocytes) are less than 1% of the blood’s volume. They are made from stem cells in bone marrow. There are five types of leukocytes, important components of the immune system. Neutrophils enter the tissue fluid by squeezing through capillary walls and phagocytozing foreign substances. Macrophages release white blood cell growth factors, causing a population increase for white blood cells. Lymphocytes fight infection. T-cells attack cells containing viruses. B-cells produce antibodies. Antigen-antibody complexes are phagocytized by a macrophage. White blood cells can squeeze through pores in the capillaries and fight infectious diseases in interstitial areas

Platelets result from cell fragmentation and are involved with clotting, as is shown by Figures 17 and 18. Platelets are cell fragments that bud off megakaryocytes in bone marrow. They carry chemicals essential to blood clotting. Platelets survive for 10 days before being removed by the liver and spleen. There are 150,000 to 300,000 platelets in each milliliter of blood. Platelets stick and adhere to tears in blood vessels; they also release clotting factors. A hemophiliac’s blood cannot clot. Providing correct proteins (clotting factors) has been a common method of treating hemophiliacs. It has also led to HIV transmission due to the use of transfusions and use of contaminated blood products.

The formation and actions of blood clots. Images from Purves et al

 

 

Blood Clot Formation

VIDEO

Diseases of the Cardiovascular System

The Lymphatic System

Water and plasma are forced from the capillaries into intracellular spaces. This interstitial fluid transports materials between cells. Most of this fluid is collected in the capillaries of a secondary circulatory system, the lymphatic system. Fluid in this system is known as lymph.

Lymph flows from small lymph capillaries into lymph vessels that are similar to veins in having valves that prevent backflow. Lymph vessels connect to lymph nodes, lymph organs, or to the cardiovascular system at the thoracic duct and right lymphatic duct.

Lymph nodes are small irregularly shaped masses through which lymph vessels flow. Clusters of nodes occur in the armpits, groin, and neck. Cells of the immune system line channels through the nodes and attack bacteria and viruses traveling in the lymph.

Myocardial infarction. Atherosclerosis. Past Perfect Revision.

Myocardial infarction

The term myocardial infarction is derived from myocardium (the heart muscle) and infarction (tissue death due to oxygen starvation). The phrase “heart attack” is sometimes used incorrectly to describe sudden cardiac death, which may or may not be the result of acute myocardial infarction..Classical symptoms of acute myocardial infarction include chest pain, shortness of breath, nausea, vomiting, palpitations, sweating, and anxiety or a feeling of impending doom. Patients frequently feel suddenly ill. Women often experience different symptoms than men. The most common symptoms of MI in women include shortness of breath, weakness, and fatigue. Approximately one third of all myocardial infarctions are silent, without chest pain or other symptoms.

Immediate treatment for suspected acute myocardial infarction includes oxygen, aspirin, glyceryl trinitrate and pain relief

 The patient will receive a number of diagnostic tests, such as an electrocardiogram (ECG, EKG), a chest X-ray and blood tests to detect elevated creatine kinase or troponin levels (these are chemical markers released by damaged tissues, especially the myocardium). Further treatment may include either medications to break down blood clots that block the blood flow to the heart, or mechanically restoring the flow by dilatation or bypass surgery of the blocked coronary artery. Coronary care unit admission allows rapid and safe treatment of complications such as abnormal heart rhythms.

Epidemiology

Myocardial infarction is a common presentation of ischemic heart disease. The WHO estimated that in 2002, 12.6% of deaths worldwide were from ischemic heart disease. Ischemic heart disease is the leading cause of death in developed countries, but third to AIDS and lower respiratory infections in developing countries.

In the United States, diseases of the heart are the leading cause of death, causing a higher mortality than cancer (malignant neoplasms). Coronary heart disease is responsible for 1 in 5 deaths in the U.S.. Some 7,200,000 men and 6,000,000 women are living with some form of coronary heart disease. 1,200,000 people suffer a (new or recurrent) coronary attack every year, and about 40% of them die as a result of the attack. This means that roughly every 65 seconds, an American dies of a coronary event.

Risk factors

Risk factors for atherosclerosis are generally risk factors for myocardial infarction:

• older age

• male gender

• cigarette smoking

• hypercholesterolemia (more accurately hyperlipoproteinemia, especially high low density lipoprotein and low high density lipoprotein)

• diabetes (with or without insulin resistance)

• high blood pressure

• obesity (defined by a body mass index of more than 30 kg/m2, or alternatively by waist circumference or waist-hip ratio).

Many of these risk factors are modifiable, so many heart attacks can be prevented by maintaining a healthier lifestyle. Physical activity, for example, is associated with a lower risk profile. Non-modifiable risk factors include age, gender, and family history of an early heart attack (before the age of 60), which is thought of as reflecting a genetic predisposition.

Socioeconomic factors such as a shorter education and lower income (particularly in women), and living with a partner may also contribute to the risk of MI. To understand epidemiological study results, it’s important to note that many factors associated with MI mediate their risk via other factors. For example, the effect of education is partially based on its effect on income and marital status.

Women who use combined oral contraceptive pills have a modestly increased risk of myocardial infarction, especially in the presence of other risk factors, such as smoking.

Inflammation is known to be an important step in the process of atherosclerotic plaque formation. C-reactive protein (CRP) is a sensitive but non-specific marker for inflammation. Elevated CRP blood levels, especially measured with high sensitivity assays, can predict the risk of MI, as well as stroke and development of diabetes. Moreover, some drugs for MI might also reduce CRP levels. The use of high sensitivity CRP assays as a means of screening the general population is advised against, but it may be used optionally at the physician’s discretion, in patients who already present with other risk factors or known coronary artery disease. Whether CRP plays a direct role in atherosclerosis remains uncertain.

Inflammation in periodontal disease may be linked coronary heart disease, and since periodontitis is very common, this could have great consequences for public health. Serological studies measuring antibody levels against typical periodontitis-causing bacteria found that such antibodies were more present in subjects with coronary heart disease.  Periodontitis tends to increase blood levels of CRP, fibrinogen and cytokines; thus, periodontitis may mediate its effect on MI risk via other risk factors. Preclinical research suggests that periodontal bacteria can promote aggregation of platelets and promote the formation of foam cells. A role for specific periodontal bacteria has been suggested but remains to be established.

Baldness, hair greying, a diagonal earlobe crease and possibly other skin features are independent risk factors for MI. Their role remains controversial; a common denominator of these signs and the risk of MI is supposed, possibly genetic.

Pathophysiology

Diagram of a myocardial infarction (2) of the tip of the anterior wall of the heart (an apical infarct) after occlusion (1) of a branch of the left coronary artery (LCA), right coronary artery = RCA

A myocardial infarction occurs when an atherosclerotic plaque slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, totally occluding the artery and preventing blood flow downstream.

Acute myocardial infarction is a type of acute coronary syndrome, which is most frequently (but not always) a manifestation of coronary artery disease. The most common triggering event is the disruption of an atherosclerotic plaque in an epicardial coronary artery, which leads to a clotting cascade, sometimes resulting in total occlusion of the artery. Atherosclerosis is the gradual buildup of cholesterol and fibrous tissue in plaques in the wall of arteries (in this case, the coronary arteries), typically over decades. Blood stream column irregularities visible on angiographies reflect artery lumearrowing as a result of decades of advancing atherosclerosis. Plaques can become unstable, rupture, and additionally promote a thrombus (blood clot) that occludes the artery; this can occur in minutes. When a severe enough plaque rupture occurs in the coronary vasculature, it leads to myocardial infarction (necrosis of downstream myocardium).

If impaired blood flow to the heart lasts long enough, it triggers a process called the ischemic cascade; the heart cells die (chiefly through necrosis) and do not grow back. A collagen scar forms in its place. Recent studies indicate that another form a cell death called apoptosis also plays a role in the process of tissue damage subsequent to myocardial infarction. As a result, the patient’s heart can be permanently damaged. This scar tissue also puts the patient at risk for potentially life threatening arrhythmias.

Injured heart tissue conducts electrical impulses more slowly thaormal heart tissue. The difference in conduction velocity between injured and uninjured tissue can trigger re-entry or a feedback loop that is believed to be the cause of many lethal arrhythmias. The most serious of these arrhythmias is ventricular fibrillation (V-Fib/VF), an extremely fast and chaotic heart rhythm that is the leading cause of sudden cardiac death. Another life threatening arrhythmia is ventricular tachycardia (V-Tach/VT), which may or may not cause sudden cardiac death. However, ventricular tachycardia usually results in rapid heart rates that prevent the heart from pumping blood effectively. Cardiac output and blood pressure may fall to dangerous levels, which is particularly bad for the patient experiencing acute myocardial infarction.

The cardiac defibrillator is a device that was specifically designed to terminate these potentially fatal arrhythmias. The device works by delivering an electrical shock to the patient in order to depolarize a critical mass of the heart muscle, in effect “rebooting” the heart. This therapy is time dependent, and the odds of successful defibrillation decline rapidly after the onset of cardiopulmonary arrest.

Triggers

Heart attack rates are higher in association with intense exertion, be it psychological stress or physical exertion, especially if the exertion is more intense than the individual usually performs. Quantitatively, the period of intense exercise and subsequent recovery is associated with about a 6-fold higher myocardial infarction rate (compared with other more relaxed time frames) for people who are physically very fit. For those in poor physical condition, the rate differential is over 35-fold higher. One observed mechanism for this phenomenon is the increased arterial pulse pressure stretching and relaxation of arteries with each heart beat which, as has been observed with intravascular ultrasound, increases mechanical “shear stress” on atheromas and the likelihood of plaque rupture.

Acute severe infection, such as pneumonia, can trigger myocardial infarction. A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.

Classification

Classification of acute coronary syndromes.

Acute myocardial infarction is a type of acute coronary syndrome, which is most frequently (but not always) a manifestation of coronary artery disease. The acute coronary syndromes include ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), and unstable angina (UA).

Depending on the location of the obstruction in the coronary circulation, different zones of the heart can become injured. Using the anatomical terms of location, one can describe anterior, inferior, lateral, apical and septal infarctions (and combinations, such as anteroinferior, anterolateral, and so on). For example, an occlusion of the left anterior descending coronary artery will result in an anterior wall myocardial infarct.

Another distinction is whether a MI is subendocardial, affecting only the inner third to one half of the heart muscle, or transmural, damaging (almost) the entire wall of the heart. The inner part of the heart muscle is more vulnerable to oxygen shortage, because the coronary arteries run inward from the epicardium to the endocardium, and because the blood flow through the heart muscle is hindered by the heart contraction.

The phrases transmural and subendocardial infarction used to be considered synonymous with Q-wave and non-Q-wave myocardial infarction respectively, based on the presence or absence of Q waves on the ECG. It has since been shown that there is no clear correlation between the presence of Q waves with a transmural infarction and the absence of Q waves with a subendocardial infarction, but Q waves are associated with larger infarctions, while the lack of Q waves is associated with smaller infarctions. The presence or absence of Q-waves also has clinical importance, with improved outcomes associated with a lack of Q waves.

The phrase massive attack is not an official medical term.

Symptoms

Rough diagram of pain zones in myocardial infarction (dark red = most typical area, light red = other possible areas, view of the chest).

Back view.

The onset of symptoms in myocardial infarction (MI) is usually gradual, over several minutes, and rarely instantaneous. Chest pain is the most common symptom of acute myocardial infarction and is often described as a sensation of tightness, pressure, or squeezing. Chest pain due to ischemia (a lack of blood and hence oxygen supply) of the heart muscle is termed angina pectoris. Pain radiates most often to the left arm, but may also radiate to the lower jaw, neck, right arm, back, and epigastrium, where it may mimic heartburn. Any group of symptoms compatible with a sudden interruption of the blood flow to the heart are called an acute coronary syndrome. Other conditions such as aortic dissection or pulmonary embolism may present with chest pain and must be considered in the differential diagnosis.

Shortness of breath (dyspnea) occurs when the damage to the heart limits the output of the left ventricle, causing left ventricular failure and consequent pulmonary edema. Other symptoms include diaphoresis (an excessive form of sweating), weakness, light-headedness, nausea, vomiting, and palpitations. Loss of consciousness and even sudden death can occur in myocardial infarctions.

Women often experience markedly different symptoms than men. The most common symptoms of MI in women include dyspnea, weakness, and fatigue. Fatigue, sleep disturbances, and dyspnea have been reported as frequently occurring symptoms which may manifest as long as one month before the actual clinically manifested ischemic event. In women, chest pain may be less predictive of coronary ischemia than in men.

Approximately half of all MI patients have experienced warning symptoms such as chest pain prior to the infarction.

Approximately one third of all myocardial infarctions are silent, without chest pain or other symptoms. These cases can be discovered later on electrocardiograms or at autopsy without a prior history of related complaints. A silent course is more common in the elderly, in patients with diabetes mellitus and after heart transplantation, probably because the donor heart is not connected to nerves of the host. In diabetics, differences in pain threshold, autonomic neuropathy, and psychological factors have been cited as possible explanations for the lack of symptoms.

Diagnosis

The diagnosis of myocardial infarction is made by integrating the history of the presenting illness and physical examination with electrocardiogram findings and cardiac markers (blood tests for heart muscle cell damage). A coronary angiogram allows to visualize narrowings or obstructions on the heart vessels, and therapeutic measures can follow immediately. At autopsy, a pathologist can diagnose a myocardial infarction based on anatomopathological findings.

 

A chest radiograph and routine blood tests may indicate complications or precipitating causes and are often performed on admittance to an emergency department. New regional wall motion abnormalities on an echocardiogram are also suggestive of a myocardial infarction and are sometimes performed in equivocal cases. Technetium and thallium can be used iuclear medicine to visualize areas of reduced blood flow and tissue viability, respectively. Technetium is used in a MUGA scan.

Diagnostic criteria

WHO criteria have classically been used to diagnose MI; a patient is diagnosed with myocardial infarction if two (probable) or three (definite) of the following criteria are satisfied:

1.     Clinical history of ischaemic type chest pain lasting for more than 20 minutes

2.     Changes in serial ECG tracings

3.     Rise and fall of serum cardiac enzymes (biomarkers) such as creatine kinase, troponin I, and lactate dehydrogenase isozymes specific for the heart.

The WHO criteria were refined in 2000 to give more prominence to cardiac biomarkers. According to the new guidelines, a cardiac troponin rise accompanied by either typical symptoms, pathological Q waves, ST elevation or depression or coronary intervention are diagnostic of MI.

Physical examination

The general appearance of patients may vary according to the experienced symptoms; the patient may be comfortable, or restless and in severe distress with an increased respiratory rate. A cool and pale skin is common and points to vasoconstriction. Some patients have low-grade fever (38–39 °C). Blood pressure may be elevated or decreased, and the pulse can be become irregular.

If heart failure ensues, elevated jugular venous pressure and hepatojugular reflux, or swelling of the legs due to peripheral edema may be found on inspection. Rarely, a cardiac bulge with a pace different from the pulse rhythm can be felt on precordial examination. Various abnormalities can be found on auscultation, such as a third and fourth heart sound, systolic murmurs, paradoxical splitting of the second heart sound, a pericardial friction rub and rales over the lung.

12-lead electrocardiogram (ECG) showing acute inferior ST segment elevation MI (STEMI). Note the ST segment elevation in leads II, III, and aVF along with reciprocal ST segment depression in leads I and aVL.

Electrocardiogram

 

The primary purpose of the electrocardiogram is to detect ischemia or acute coronary injury in broad, symptomatic emergency department populations. However, the standard 12 lead ECG has several limitations. An ECG represents a brief sample in time. Because unstable ischemic syndromes have rapidly changing supply versus demand characteristics, a single ECG may not accurately represent the entire picture. It is therefore desirable to obtain serial 12 lead ECGs, particularly if the first ECG is obtained during a pain-free episode. Alternatively, many emergency departments and chest pain centers use computers capable of continuous ST segment monitoring. It should also be appreciated that the standard 12 lead ECG does not directly examine the right ventricle, and does a relatively poor job of examining the posterior basal and lateral walls of the left ventricle. In particular, acute myocardial infarction in the distribution of the circumflex artery is likely to produce a nondiagnostic ECG. The use of non-standard ECG leads like right-sided lead V4R and posterior leads V7, V8, and V9 may improve sensitivity for right ventricular and posterior myocardial infarction. In spite of these limitations, the 12 lead ECG stands at the center of risk stratification for the patient with suspected acute myocardial infarction. Mistakes in interpretation are relatively common, and the failure to identify high risk features has a negative effect on the quality of patient care. The 12 lead ECG is used to classify patients into one of three groups:

1. those with ST segment elevation or new bundle branch block (suspicious for acute injury and a possible candidate for acute reperfusion therapy with thrombolytics or primary PCI),

2. those with ST segment depression or T wave inversion (suspicious for ischemia), and

3. those with a so-called non-diagnostic or normal ECG.

The presence of ST segment elevation distinguishes between:

• STEMI (“ST-Elevation Myocardial Infarction”)

• NSTEMI (“Non-ST-Elevation Myocardial Infarction”) — diagnosed when cardiac enzymes are elevated.

The leads with ST segment elevation help the clinician identify what area of the heart is infarcting. It also enables the clinician to predict the culprit artery:

Cardiac markers

Cardiac markers or cardiac enzymes are proteins from cardiac tissue found in the blood. These proteins are released into the bloodstream when damage to the heart occurs, as in the case of a myocardial infarction. Until the 1980s, the enzymes SGOT and LDH were used to assess cardiac injury. Then it was found that disproportional elevation of the MB subtype of the enzyme creatine kinase (CK) was very specific for myocardial injury. Current guidelines are generally in favor of troponin sub-units I or T, which are very specific for the heart muscle and are thought to rise before permanent injury develops. Elevated troponins in the setting of chest pain may accurately predict a high likelihood of a myocardial infarction in the near future.

The diagnosis of myocardial infarction requires two out of three components (history, ECG, and enzymes). When damage to the heart occurs, levels of cardiac markers rise over time, which is why blood tests for them are taken over a 24 hour period. Because these enzyme levels are not elevated immediately following a heart attack, patients presenting with chest pain are generally treated with the assumption that a myocardial infarction has occurred and then evaluated for a more precise diagnosis.

Angiography

Angiogram of the coronary arteries.

In difficult cases or in situations where intervention to restore blood flow is appropriate, coronary angiography can be performed. A catheter is inserted into an artery (usually the femoral artery) and pushed to the vessels supplying the heart. Obstructed or narrowed arteries can be identified, and angioplasty applied as a therapeutic measure (see below). Angioplasty requires extensive skill, especially in emergency settings, and may not always be available out of hours. It is commonly performed by interventional cardiologists.

Histopathology

Micrograph showing contraction band necrosis, a histopathologic finding of myocardial infarction (heart attack).

Microscopy image (magn. ca 100x, H&E stain) from autopsy specimen of myocardial infarct (7 days post-infarction).

Histopathological examination of the heart may reveal infarction at autopsy. Under the microscope, myocardial infarction presents as a circumscribed area of ischemic, coagulative necrosis (cell death). On gross examination, the infarct is not identifiable within the first 12 hours.

Although earlier changes can be discerned using electron microscopy, one of the earliest changes under a normal microscope are so-called wavy fibers. Subsequently, the myocyte cytoplasm becomes more eosinophilic (pink) and the cells lose their transversal striations, with typical changes and eventually loss of the cell nucleus. The interstitium at the margin of the infarcted area is initially infiltrated with neutrophils, then with lymphocytes and macrophages, who phagocytose (“eat”) the myocyte debris. The necrotic area is surrounded and progressively invaded by granulation tissue, which will replace the infarct with a fibrous (collagenous) scar (which are typical steps in wound healing). The interstitial space (the space between cells outside of blood vessels) may be infiltrated with red blood cells. These features can be recognized in cases where the perfusion was not restored; reperfused infarcts can have other hallmarks, such as contraction band necrosis.

First aid

As myocardial infarction is a common medical emergency, the signs are often part of first aid courses. The emergency action principles also apply in the case of myocardial infarction.

 Immediate care

When symptoms of myocardial infarction occur, people wait on average of 3 hours, instead of doing what is recommended: calling for help immediately. Acting immediately by calling the emergency services can prevent sustained damage to the heart (“time is muscle”).

 

 

Certain positions allow the patient to rest in a position which minimizes breathing difficulties. A half-sitting position with knees bent is often recommended. Access to more oxygen can be given by opening the window and widening the collar for easier breathing.

Aspirin can be given quickly (if the patient is not allergic to aspirin); but taking aspirin before calling the emergency medical services may be associated with unwanted delay. Aspirin has an antiplatelet effect which inhibits formation of further thrombi (blood clots) that clog arteries. Non-enteric coated or soluble preparations are preferred. If chewed or dissolved, respectively, they can be absorbed by the body even quicker. If the patient cannot swallow, the aspirin can be used sublingually. U.S. guidelines recommend a dose of 162 – 325 mg. Australian guidelines recommend a dose of 150 – 300 mg.

Glyceryl trinitrate (nitroglycerin) sublingually (under the tongue) can be given if it has been prescribed for the patient.

If an AED is available the rescuer should immediately bring the AED to the patient’s side and be prepared to follow its instructions should the victim lose consciousness.

If possible the rescuer should obtain basic information from the victim, in case the patient is unable to answer questions once emergency medical technicians arrive (if the patient becomes unconscious). The victim’s name and any information regarding the nature of the victims pain will useful to health care providers. Also the exact time that these symptoms started, what the patient was doing at the onset of symptoms, and anything else that might give clues to the pathology of the chest pain. It is also very important to relay any actions that have been taken, such as the number or dose of aspirin or nitroglycerin given, to the EMS personnel.

Other general first aid principles include monitoring pulse, breathing, level of consciousness and, if possible, the blood pressure of the patient. In case of cardiac arrest, cardiopulmonary resuscitation (CPR) can be administered.

Automatic external defibrillation (AED)

Since the publication of data showing that the availability of automated external defibrillators (AEDs) in public places may significantly increase chances of survival, many of these have been installed in public buildings, public transport facilities, and in non-ambulance emergency vehicles (e.g. police cars and fire engines). AEDs analyze the heart’s rhythm and determine whether the rhythm is amenable to defibrillation (“shockable”), as in ventricular tachycardia and ventricular fibrillation.

Emergency services

Emergency Medical Services (EMS) Systems vary considerably in their ability to evaluate and treat patients with suspected acute myocardial infarction. Some provide as little as first aid and early defibrillation. Others employ highly trained paramedics with sophisticated technology and advanced protocols. Early access to EMS is promoted by a 9-1-1 system currently available to 90% of the population in the United States. Most are capable of providing oxygen, IV access, sublingual nitroglycerine, morphine, and aspirin. Some are capable of providing thrombolytic therapy in the prehospital setting.

With primary PCI emerging as the preferred therapy for ST segment elevation myocardial infarction, EMS can play a key role in reducing door to balloon intervals (the time from presentation to a hospital ER to the restoration of coronary artery blood flow) by performing a 12 lead ECG in the field and using this information to triage the patient to the most appropriate medical facility. In addition, the 12 lead ECG can be transmitted to the receiving hospital, which enables time saving decisions to be made prior to the patient’s arrival. This may include a “cardiac alert” or “STEMI alert” that calls in off duty personnel in areas where the cardiac cath lab is not staffed 24 hours a day. Even in the absence of a formal alerting program, prehospital 12 lead ECGs are independently associated with reduced door to treatment intervals in the emergency department.

Wilderness first aid

In wilderness first aid, a possible heart attack justifies evacuation by the fastest available means, including MEDEVAC, even in the earliest or precursor stages. The patient will rapidly be incapable of further exertion and have to be carried out.

Air travel

Certified personnel traveling by commercial aircraft may be able to assist an MI patient by using the on-board first aid kit, which may contain some cardiac drugs (such as glyceryl trinitrate spray, aspirin, or opioid painkillers) and oxygen. Pilots may divert the flight to land at a nearby airport. Cardiac monitors are being introduced by some airlines, and they can be used by both on-board and ground-based physicians.

Treatment

A heart attack is a medical emergency which demands both immediate attention and activation of the emergency medical services. The ultimate goal of the management in the acute phase of the disease is to salvage as much myocardium as possible and prevent further complications. As time passes, the risk of damage to the heart muscle increases; hence the phrase that in myocardial infarction, “time is muscle”, and time wasted is muscle lost.

The treatments itself may have complications. If attempts to restore the blood flow are initiated after a critical period of only a few hours, the result is reperfusion injury instead of amelioration. Other treatment modalities may also cause complications; the use of antithrombotics for example carries an increased risk of bleeding.

First line

 

Oxygen, aspirin, glyceryl trinitrate (nitroglycerin) and analgesia (usually morphine, hence the popular mnemonic MONA, morphine, oxygen, nitro, aspirin) are administered as soon as possible. In many areas, first responders can be trained to administer these prior to arrival at the hospital.

Of the first line agents, only aspirin has been proven to decrease mortality.

Once the diagnosis of myocardial infarction is confirmed, other pharmacologic agents are often given. These include beta blockers, anticoagulation (typically with heparin), and possibly additional antiplatelet agents such as clopidogrel. These agents are typically not started until the patient is evaluated by an emergency room physician or under the direction of a cardiologist. These agents can be used regardless of the reperfusion strategy that is to be employed. While these agents can decrease mortality in the setting of an acute myocardial infarction, they can lead to complications and potentially death if used in the wrong setting.

Reperfusion

The concept of reperfusion has become so central to the modern treatment of acute myocardial infarction, that we are said to be in the reperfusion era. Patients who present with suspected acute myocardial infarction and ST segment elevation (STEMI) or new bundle branch block on the 12 lead ECG are presumed to have an occlusive thrombosis in an epicardial coronary artery. They are therefore candidates for immediate reperfusion, either with thrombolytic therapy, percutaneous coronary intervention (PCI) or when these therapies are unsuccessful, bypass surgery.

Individuals without ST segment elevation are presumed to be experiencing either unstable angina (UA) or non-ST segment elevation myocardial infarction (NSTEMI). They receive many of the same initial therapies and are often stabilized with antiplatelet drugs and anticoagulated. If their condition remains (hemodynamically) stable, they can be offered either late coronary angiography with subsequent restoration of blood flow (revascularization), or non-invasive stress testing to determine if there is significant ischemia that would benefit from revascularization. If hemodynamic instability develops in individuals with NSTEMIs, they may undergo urgent coronary angiography and subsequent revascularization. The use of thrombolytic agents is contraindicated in this patient subset, however.

The basis for this distinction in treatment regimens is that ST segment elevations on an ECG are typically due to complete occlusion of a coronary artery. On the other hand, in NSTEMIs there is typically a suddearrowing of a coronary artery with preserved (but diminished) flow to the distal myocardium. Anticoagulation and antiplatelet agents are given to prevent the narrowed artery from occluding.

At least 10% of patients with STEMI don’t develop myocardial necrosis (as evidenced by a rise in cardiac markers) and subsequent q waves on EKG after reperfusion therapy. Such a successful restoration of flow to the infarct-related artery during an acute myocardial infarction is known as “aborting” the myocardial infarction. If treated within the hour, about 25% of STEMIs can be aborted.

Thrombolytic therapy

Thrombolytic therapy is indicated for the treatment of STEMI if the drug can be administered within 12 hours of the onset of symptoms, the patient is eligible based on exclusion criteria, and primary PCI is not immediately available. The effectiveness of thombolytic therapy is highest in the first 2 hours. After 12 hours, the risk associated with thrombolytic therapy outweighs any benefit. Because irreversible injury occurs within 2–4 hours of the infarction, there is a limited window of time available for reperfusion to work.

Thrombolytic drugs are contraindicated for the treatment of unstable angina and NSTEMI and for the treatment of individuals with evidence of cardiogenic shock.

Although no perfect thrombolytic agent exists, an ideal thrombolytic drug would lead to rapid reperfusion, have a high sustained patency rate, be specific for recent thrombi, be easily and rapidly administered, create a low risk for intra-cerebral and systemic bleeding, have no antigenicity, adverse hemodynamic effects, or clinically significant drug interactions, and be cost effective. Currently available thrombolytic agents include streptokinase, urokinase, and alteplase (recombinant tissue plasminogen activator, rtPA). More recently, thrombolytic agents similar in structure to rtPA such as reteplase and tenecteplase have been used. These newer agents boast efficacy at least as good as rtPA with significantly easier administration. The thrombolytic agent used in a particular individual is based on institution preference and the age of the patient.

Depending on the thrombolytic agent being used, adjuvant anticoagulation with heparin or low molecular weight heparin may be of benefit. With tPA and related agents (reteplase and tenecteplase), heparin is needed to maintain coronary artery patency. Because of the anticoagulant effect of fibrinogen depletion with streptokinase and urokinase treatment, it is less necessary there.

Thrombolytic therapy to abort a myocardial infarction is not always effective, and has a 10-20% failure rate. In cases of failure of the thrombolytic agent to open the infarct-related coronary artery, the patient is then either treated conservatively with anticoagulants and allowed to “complete the infarction” or percutaneous coronary intervention (PCI, see below) is then performed. Percutaneous coronary intervention in this setting is known as “rescue PCI” or “salvage PCI”. Complications, particularly bleeding, are significantly higher with rescue PCI than with primary PCI due to the action of the thrombolytic agent.

Percutaneous coronary intervention

Thrombus material (in a cup, upper left corner) removed from a coronary artery during a percutaneous coronary intervention to abort a myocardial infarction. Five pieces of thrombus are shown (arrow heads).

Although clinical trials suggest better outcomes compared to thrombolytic therapy, logistic and economic obstacles seem to hinder a more widespread application of percutaneous coronary intervention (PCI) via cardiac catheterization. The use of percutaneous coronary intervention as a therapy to abort a myocardial infarction is known as primary PCI. The goal of primary PCI is to open the artery as soon as possible, and preferably within 90 minutes of the patient presenting to the emergency room. This time is referred to as the door-to-balloon time. Few hospitals can provide PCI within the 90 minute interval.

The current guidelines in the United States restrict primary PCI to hospitals with available emergency bypass surgery as a backup, but this is not the case in other parts of the world.

Primary PCI involves performing a coronary angiogram to determine the anatomical location of the infarcting vessel, followed by balloon angioplasty (and frequently deployment of an intracoronary stent) of the thrombosed arterial segment. In some settings, an extraction catheter may be used to attempt to aspirate (remove) the thrombus prior to balloon angioplasty. While the use of intracoronary stents do not improve the short term outcomes in primary PCI, the use of stents is widespread because of the decreased rates of procedures to treat restenosis compared to balloon angioplasty.

Adjuvent therapy during primary PCI include intravenous heparin, aspirin, and clopidogrel. The use of glycoprotein IIb/IIIa inhibitors are often used in the setting of primary PCI to reduce the risk of ischemic complications during the procedure. Due to the number of antiplatelet agents and anticoagulants used during primary PCI, the risk of bleeding associated with the procedure are higher than during an elective PCI.

Coronary artery bypass surgery

Coronary artery bypass surgery during mobilization (freeing) of the right coronary artery from its surrounding tissue, adipose tissue (yellow). The tube visible at the bottom is the aortic cannula (returns blood from the HLM). The tube above it (obscured by the surgeon on the right) is the venous cannula (receives blood from the body). The patient’s heart is stopped and the aorta is cross-clamped. The patient’s head (not seen) is at the bottom.

Monitoring for arrhythmias

Additional objectives are to prevent life-threatening arrhythmias or conduction disturbances. This requires monitoring in a coronary care unit and protocolised administration of antiarrhythmic agents. Antiarrhythmic agents are typically only given to individuals with life-threatening arrhythmias after a myocardial infarction and not to suppress the ventricular ectopy that is often seen after a myocardial infarction.

Rehabilitation

Cardiac rehabilitation aims to optimize function and quality of life in those afflicted with a heart disease. This can be with the help of a physician, or in the form of a cardiac rehabilitation program.

Physical exercise is an important part of rehabilitation after a myocardial infarction, with beneficial effects on cholesterol levels, blood pressure, weight, stress and mood. Some patients become afraid of exercising because it might trigger another infarct. Patients are stimulated to exercise, and should only avoid certain exerting activities such as shovelling. Local authorities may place limitations on driving motorised vehicles. Some people are afraid to have sex after a heart attack. Most people can resume sexual activities after 3 to 4 weeks. The amount of activity needs to be dosed to the patients possibilities.

Secondary prevention

The risk of a recurrent myocardial infarction decreases with strict blood pressure management and lifestyle changes, chiefly smoking cessation, regular exercise, a sensible diet for patients with heart disease, and limitation of alcohol intake.

Patients are usually commenced on several long-term medications post-MI, with the aim of preventing secondary cardiovascular events such as further myocardial infarctions, congestive heart failure or cerebrovascular accident (CVA). Unless contraindicated, such medications may include:

•        Antiplatelet drug therapy such as aspirin and/or clopidogrel should be continued to reduce the risk of plaque rupture and recurrent myocardial infarction. Aspirin is first-line, owing to its low cost and comparable efficacy, with clopidogrel reserved for patients intolerant of aspirin. The combination of clopidogrel and aspirin may further reduce risk of cardiovascular events, however the risk of hemorrhage is increased.

•        Beta blocker therapy such as metoprolol or carvedilol should be commenced. These have been particularly beneficial in high-risk patients such as those with left ventricular dysfunction and/or continuing cardiac ischaemia. β-Blockers decrease mortality and morbidity. They also improve symptoms of cardiac ischemia in NSTEMI.

•        ACE inhibitor therapy should be commenced 24–48 hours post-MI in hemodynamically-stable patients, particularly in patients with a history of MI, diabetes mellitus, hypertension, anterior location of infarct (as assessed by ECG), and/or evidence of left ventricular dysfunction. ACE inhibitors reduce mortality, the development of heart failure, and decrease ventricular remodelling post-MI.

•        Statin therapy has been shown to reduce mortality and morbidity post-MI. The effects of statins may be more than their LDL lowering effects. The general consensus is that statins have plaque stabilization and multiple other (“pleiotropic”) effects that may prevent myocardial infarction in addition to their effects on blood lipids.

•        The aldosterone antagonist agent eplerenone has been shown to further reduce risk of cardiovascular death post-MI in patients with heart failure and left ventricular dysfunction, when used in conjunction with standard therapies above.

•        Omega-3 fatty acids, commonly found in fish, have been shown to reduce mortality post-MI. While the mechanism by which these fatty acids decrease mortality is unknown, it has been postulated that the survival benefit is due to electrical stabilization and the prevention of ventricular fibrillation. However, further studies in a high-risk subset have not shown a clear-cut decrease in potentially fatal arrhythmias due to omega-3 fatty acids.

New therapies under investigation

Patients who receive stem cell treatment by coronary artery injections of stem cells derived from their own bone marrow after a myocardial infarction (MI) show improvements in left ventricular ejection fraction and end-diastolic volume not seen with placebo. The larger the initial infarct size, the greater the effect of the infusion. Clinical trials of progenitor cell infusion as a treatment approach to ST elevation MI are proceeding.

There are currently 3 biomaterial and tissue engineering approaches for the treatment of MI, but these are in an even earlier stage of medical research, so many questions and issues need to be addressed before they can be applied to patients. The first involves polymeric left ventricular restraints in the prevention of heart failure. The second utilizes in vitro engineered cardiac tissue, which is subsequently implanted in vivo. The final approach entails injecting cells and/or a scaffold into the myocardium to create in situ engineered cardiac tissue.

Complications

Complications may occur immediately following the heart attack (in the acute phase), or may need time to develop (a chronic problem). After an infarction, an obvious complication is a second infarction, which may occur in the domain of another atherosclerotic coronary artery, or in the same zone if there are any live cells left in the infarct.

Congestive heart failure

A myocardial infarction may compromise the function of the heart as a pump for the circulation, a state called heart failure. There are different types of heart failure; left- or right-sided (or bilateral) heart failure may occur depending on the affected part of the heart, and it is a low-output type of failure. If one of the heart valves is affected, this may cause dysfunction, such as mitral regurgitation in the case of left-sided MI. The incidence of heart failure is particularly high in patients with diabetes and requires special management strategies.

Cardiogenic shock

A complication that may occur in the acute setting soon after a myocardial infarction or in the weeks following it is cardiogenic shock. Cardiogenic shock is defined as a hemodynamic state in which the heart cannot produce enough of a cardiac output to supply an adequate amout of oxygenated blood to the tissues of the body.

While the data on performing interventions on individuals with cardiogenic shock is sparse, trial data suggests a long-term mortality benefit in undergoing revascularization if the individual is less than 75 years old and if the onset of the acute myocardial infarction is less than 36 hours and the onset of cardiogenic shock is less than 18 hours. If the patient with cardiogenic shock is not going to be revascularized, aggressive hemodynamic support is warranted, with insertion of an intra-aortic balloon pump if not contraindicated.

Prognosis

The prognosis for patients with myocardial infarction varies greatly, depending on the patient, the condition itself and the given treatment. Using simple variables which are immediately available in the emergency room, patients with a higher risk of adverse outcome can be identified. For example, one study found that 0.4% of patients with a low risk profile had died after 90 days, whereas the mortality rate in high risk patients was 21.1%.

Although studies differ in the identified variables, some of the more reproduced risk stratifiers include age, hemodynamic parameters (such as heart failure, cardiac arrest on admission, systolic blood pressure, or Killip class of two or greater), ST-segment deviation, diabetes, serum creatinine concentration, peripheral vascular disease and elevation of cardiac markers.

Assesment of left ventricular ejection fraction may increase the predictive power of some risk stratification models. The prognostic importance of Q-waves is debated. Prognosis is significantly worsened if a mechanical complication (papillary muscle rupture, myocardial free wall rupture, and so on) were to occur. There is evidence that case fatality of myocardial infarction has been improving over the years in all ethnicities.

Legal implications

At common law, a myocardial infarction is generally a disease, but may sometimes be an injury. This has implications for no-fault insurance schemes such as workers’ compensation. A heart attack is generally not covered, however, it may be a work-related injury if it results, for example, from unusual emotional stress or unusual exertion. Additionally, in some jurisdictions, heart attacks suffered by persons in particular occupations such as police officers may be classified as line-of-duty injuries by statute or policy. In some countries or states, a person who has suffered from a myocardial infarction may be prevented from participating in activity that puts other people’s lives at risk, for example driving a car, taxi or airplane.

In medicine, infarction refers to tissue death (necrosis) caused by an obstruction of the tissue’s blood supply, which leads to a local lack of oxygen.^[The resulting lesion is referred to as an infarct(from the Latin infarctus, “stuffed into”).

 

Micrograph of a pulmonary infarct (right of image) beside relatively normal lung (left of image). H&E stain.

Causes

The supplying artery may be blocked by an obstruction (e.g., an arterial embolus, thrombus, or atherosclerotic plaque), may be mechanically compressed (e.g., tumor, volvulus, or hernia), ruptured by trauma (e.g., atherosclerosis or vasculitides), or vasoconstricted (e.g., cocaine vasoconstriction leading to myocardial infarction).

Hypertension and atherosclerosis are risk factors for both atherosclerotic plaques and thromboembolism. In atherosclerotic formations, a plaque develops under a fibrous cap. When the fibrous cap is degraded by metalloproteinases released from macrophages or by intravascular shear force from blood flow, subendothelial thrombogenic material (extracellular matrix) is exposed to circulating platelets and thrombus formation occurs on the vessel wall occluding blood flow. Occasionally, the plaque may rupture and form an embolus which travels with the blood-flow downstream to where the vessel narrows and eventually clogs the vessel lumen.

Infarctions can also involve mechanical blockage of the blood supply, such as when part of the gut or testicles herniates or becomes involved in a volvulus.

Classification

By histopathology

Infarctions are divided into 2 types according to the amount of blood present:

• White infarctions (anemic infarcts) affect solid organs such as the spleen, heart and kidneys wherein the solidity of the tissue substantially limits the amount of nutrients (blood/oxygen/glucose/fuel) that can flow into the area of ischemic necrosis. Similar occlusion to blood flow and consequent necrosis can occur as a result of severe vasoconstriction as illustrated in severe Raynaud’s phenomenon that can lead to irreversible gangrene.

• Red infarctions (hemorrhagic infarcts), generally affect the lungs or other loose organs (testis, ovary, small intestines). The occlusion consists more of red blood cells and fibrin strands. Characteristics of red infarcts include:

• occlusion of a vein

• loose tissues that allow blood to collect in the infarcted zone

• tissues with a dual circulatory system (lung, small intestines)

• tissues previously congested from sluggish venous outflow

• reperfusion (injury) of previously ischemic tissue that is associated with reperfusion-related diseases such as – Myocardial infarction, stroke (cerebral infarction), shock-resuscitation, replantation surgery, frostbite, burns and organ transplantation.

By localization

• Heart: Myocardial infarction (MI), commonly known as a heart attack, is an infarction of the heart, causing some heart cells to die. This is most commonly due to occlusion (blockage) of a coronary artery following the rupture of a vulnerable atherosclerotic plaque, which is an unstable collection of lipids (fatty acids) and white blood cells (especially macrophages) in the wall of an artery. The resulting ischemia (restriction in blood supply) and oxygen shortage, if left untreated for a sufficient period of time, can cause damage or death of heart muscle tissue (myocardium).

• Brain: Cerebral infarction is the ischemic kind of stroke due to a disturbance in the blood vessels supplying blood to the brain. It can be atherothrombotic or embolic. Stroke caused by cerebral infarction should be distinguished from two other kinds of stroke: cerebral hemorrhage and subarachnoid hemorrhage. Cerebral infarctions vary in their severity with one third of the cases resulting in death.

• Lung: Pulmonary infarction or lung infarction

• Spleen: Splenic infarction occurs when the splenic artery or one of its branches are occluded, for example by a blood clot. Although it can occur asymptomatically, the typical symptom is severe pain in the left upper quadrant of the abdomen, sometimes radiating to the left shoulder. Fever and chills develop in some cases.It has to be differentiated from other causes of acute abdomen.

• Limb: Limb infarction is an infarction of an arm or leg. Causes include arterial embolisms and skeletal muscle infarction as a rare complication of long standing, poorly controlled diabetes mellitus. A major presentation is painful thigh or leg swelling.

• Bone: Infarction of bone results in avascular necrosis. Without blood, the bone tissue dies and the bone collapses. If avascular necrosis involves the bones of a joint, it often leads to destruction of the joint articular surfaces (see osteochondritis dissecans).

• Testicle: an infarction of a testicle may be caused by testicular torsion.

 

Ultrasound of segmental testicular infarction. Infarct area shown as hypoechoic and avascular upper segment of R testis.

• Eye: an infarction can occur to the central retinal artery which supplies the retina causing sudden visual loss.

Associated diseases

Diseases commonly associated with infarctions include:

Peripheral artery occlusive disease (the most severe form of which is gangrene). Peripheral vascular disease (PVD), commonly referred to as peripheral artery disease (PAD) or peripheral artery occlusive disease (PAOD), refers to the obstruction of large arteries not within the coronary, aortic arch vasculature, or brain. PVD can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism, or thrombus formation. It causes either acute or chronic ischemia (lack of blood supply). Often PVD is a term used to refer to atherosclerotic blockages found in the lower extremity.

PVD also includes a subset of diseases classified as microvascular diseases resulting from episodal narrowing of the arteries (Raynaud’s phenomenon), or widening thereof (erythromelalgia), i.e. vascular spasms.

Classification

Peripheral artery occlusive disease is commonly divided in the Fontaine stages, introduced by René Fontaine in 1954 for ischemia:

1.     mild pain when walking (claudication), incomplete blood vessel obstruction;

2.     severe pain when walking relatively short distances (intermittent claudication), pain triggered by walking “after a distance of >150 m in stage IIa and after <150 m in stage II-b”;

3.     pain while resting (rest pain), mostly in the feet, increasing when the limb is raised;

4.     biological tissue loss (gangrene) and difficulty walking.

A more recent classification by Rutherford consists of three grades and six categories:

1.     Mild claudication

2.     Moderate claudication

3.     Severe claudication

4.     Ischemic pain at rest

5.     Minor tissue loss

6.     Major tissue loss

Symptoms

About 20% of patients with mild PAD may be asymptomatic; other symptoms include:

• Claudication – pain, weakness, numbness, or cramping in muscles due to decreased blood flow

• Sores, wounds, or ulcers that heal slowly or not at all

• Noticeable change in color (blueness or paleness) or temperature (coolness) when compared to the other limb (termed unilateral dependent rubor; when both limbs are affected this is termed bilateral dependent rubor)

• Diminished hair and nail growth on affected limb and digits.

Causes

Risk factors contributing to PAD are the same as those for atherosclerosis:

• Smoking – tobacco use in any form is the single most important modifiable cause of PVD internationally. Smokers have up to a tenfold increase in relative risk for PVD in a dose-related effect. Exposure to second-hand smoke from environmental exposure has also been shown to promote changes in blood vessel lining (endothelium) which is a precursor to atherosclerosis.

• Diabetes mellitus – causes between two and four times increased risk of PVD by causing endothelial and smooth muscle cell dysfunction in peripheral arteries. Diabetics account for up to 70% of nontraumatic amputations performed, and a known diabetic who smokes runs an approximately 30% risk of amputation within 5 years.

• Dyslipidemia (high low density lipoprotein [LDL] cholesterol, low high density lipoprotein [HDL] cholesterol) – elevation of total cholesterol, LDL cholesterol, and triglyceride levels each have been correlated with accelerated PAD. Correction of dyslipidemia by diet and/or medication is associated with a major improvement in short-term rates of heart attack and stroke. This benefit is gained even though current evidence does not demonstrate a major reversal of peripheral and/or coronary atherosclerosis.

• Hypertension – elevated blood pressure is correlated with an increase in the risk of developing PAD, as well as in associated coronary and cerebrovascular events (heart attack and stroke).

• Risk of PAD also increases in individuals who are over the age of 50, male, obese, or with a family history of vascular disease, heart attack, or stroke.

• Other risk factors which are being studied include levels of various inflammatory mediators such as C-reactive protein, homocysteine.

Diagnosis

Upon suspicion of PVD, the first-line study is the ankle brachial pressure index (ABPI/ABI). When the blood pressure readings in the ankles is lower than that in the arms, blockages in the arteries which provide blood from the heart to the ankle are suspected. An ABI ratio less than 0.9 is consistent with PVD; values of ABI below 0.8 indicate moderate disease and below 0.5 imply severe ischemic disease, alternatively 0.4 is used as a threshold.

It is possible for conditions which stiffen the vessel walls (such as calcifications that occur in the setting of chronic diabetes) to produce false negatives usually, but not always, indicated by abnormally high ABIs (> 1.3). Such results and suspicions merit further investigation and higher level studies.

If ABIs are abnormal the next step is generally a lower limb doppler ultrasound examination to look at site and extent of atherosclerosis. Other imaging can be performed by angiography,^[1] where a catheter is inserted into the common femoral artery and selectively guided to the artery in question. While injecting a radiodense contrast agent an X-ray is taken. Any flow limiting stenoses found in the x-ray can be identified and treated by atherectomy, angioplasty or stenting.

Modern multislice computerized tomography (CT) scanners provide direct imaging of the arterial system as an alternative to angiography. CT provides complete evaluation of the aorta and lower limb arteries without the need for an angiogram’s arterial injection of contrast agent.

Treatment

Dependent on the severity of the disease, the following steps can be taken:

• Smoking cessation (cigarettes promote PVD and are a risk factor for cardiovascular disease).

• Management of diabetes.

• Management of hypertension.

• Management of cholesterol, and medication with antiplatelet drugs. Medication with aspirin, clopidogrel and statins, which reduce clot formation and cholesterol levels, respectively, can help with disease progression and address the other cardiovascular risks that the patient is likely to have.

• Regular exercise for those with claudication helps open up alternative small vessels (collateral flow) and the limitation in walking often improves. Treadmill exercise (35 to 50 minutes, 3 to 4 times per week) has been reviewed as another treatment with a number of positive outcomes including reduction in cardiovascular events and improved quality of life.

• Cilostazol or pentoxifylline treatment to relieve symptoms of claudication.

Treatment with other drugs or vitamins are unsupported by clinical evidence, “but trials evaluating the effect of folate and vitamin B-12 on hyperhomocysteinaemia, a putative vascular risk factor, are near completion”.

After a trial of the best medical treatment outline above, if symptoms remain unnacceptable, patients may be referred to a vascular or endovascular surgeon; however, “No convincing evidence supports the use of percutaneous balloon angioplasty or stenting in patients with intermittent claudication”.

• Angioplasty (PTA or percutaneous transluminal angioplasty) can be done on solitary lesions in large arteries, such as the femoral artery, but angioplasty may not have sustained benefits.

• Plaque excision, in which the plaque is scraped off of the inside of the vessel wall.

• Occasionally, bypass grafting is needed to circumvent a seriously stenosed area of the arterial vasculature. Generally, the saphenous vein is used, although artificial (Gore-Tex) material is often used for large tracts when the veins are of lesser quality.

• Rarely, sympathectomy is used – removing the nerves that make arteries contract, effectively leading to vasodilatation.

• When gangrene of toes has set in, amputation is often a last resort to stop infected dying tissues from causing septicemia.

• Arterial thrombosis or embolism has a dismal prognosis, but is occasionally treated successfully with thrombolysis.

Guidelines

Several different guideline standards have been developed, including:

• TASC II Guidelines

• ACC/AHA Guidelines

Prognosis

Individuals with PAD have an “exceptionally elevated risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology”; prognosis is correlated with the severity of the PAD as measured by the Ankle brachial pressure index (ABPI). Large-vessel PAD increases mortality from cardiovascular disease significantly. PAD carries a greater than “20% risk of a coronary event in 10 years”.

There is a low risk that an individual with claudication will develop severe ischemia and require amputation, but the risk of death from coronary events is three to four times higher than matched controls without claudication. Of patients with intermittent claudication, only “7% will undergo lower extremity bypass surgery, 4% major amputations, and 16% worsening claudication”, but stroke and heart attack events are elevated, and the “5-year mortality rate is estimated to be 30% (versus 10% in controls)”.

Epidemiology

The prevalence of peripheral vascular disease in the general population is 12–14%, affecting up to 20% of those over 70;^[12] 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Peripheral vascular disease affects 1 in 3 diabetics over the age of 50.

In the USA peripheral arterial disease affects 12–20 percent of Americans age 65 and older. Approximately 10 million Americans have PVD. Despite its prevalence and cardiovascular risk implications, only 25 percent of PAD patients are undergoing treatment.

The incidence of symptomatic PVD increases with age, from about 0.3% per year for men aged 40–55 years to about 1% per year for men aged over 75 years. The prevalence of PVD varies considerably depending on how PAD is defined, and the age of the population being studied. Diagnosis is critical, as people with PAD have a four to five times higher risk of heart attack or stroke.

The Diabetes Control and Complications Trial and U.K. Prospective Diabetes Study trials in people with type 1 and type 2 diabetes, respectively, demonstrated that glycemic control is more strongly associated with microvascular disease than macrovascular disease. It may be that pathologic changes occurring in small vessels are more sensitive to chronically elevated glucose levels than is atherosclerosis occurring in larger arteries.^[13]

Antiphospholipid syndrome. Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS or), often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against β₂ glycoprotein I (a plasma protein without a clear function) that provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, or severe preeclampsia. People without the protein seem to be completely healthy. In particular, the disease is characterised by antibodies against cardiolipin (anti-cardiolipin antibodies) and β₂ glycoprotein I.

The term “primary antiphospholipid syndrome” is used when APS occurs in the absence of any other related disease. APS however also occurs in the context of other autoimmune diseases, such as systemic lupus erythematosus (SLE), in which case the term “secondary antiphospholipid syndrome” is used. In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed “catastrophic antiphospholipid syndrome” (CAPS) and is associated with a high risk of death.

Antiphospholipid syndrome is diagnosed with blood tests. It often requires treatment with anticoagulant medication such as heparin to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. Warfarin/Coumadin is not used during pregnancy because it can cross the placenta, unlike heparin, and is teratogenic.

Signs and symptoms

The presence of antiphospholipid antibodies (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS).

Antiphospholipid syndrome can cause arterial or venous blood clots, in any organ system, or pregnancy-related complications. In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most common arterial event is stroke. In pregnant women affected by APS, miscarriage can occur prior to 20 week of gestation, while pre-eclampsia is reported to occur after that time. Placental infarctions, early deliveries and stillbirth are also reported in women with APS. In some cases, APS seems to be the leading cause of mental and/or development retardation in the newborn, due to an aPL-induced inhibition of trophoblast differentiation. The antiphospholipid syndrome responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.

Other common findings, although not part of the APS classification criteria, are thrombocytopenia, heart valve disease, and livedo reticularis. There are also associations between antiphospholipid antibodies and headaches, migraines, and oscillopsia. Some studies have shown the presence of antiphospholipid antibodies in the blood and spinal fluid of patients with psychological symptoms.

Very few patients with primary APS go on to develop SLE.

Risk factors

Risk factors for developing antiphospholipid syndrome include:

• Primary APS

• genetic marker HLA-DR7

• Secondary APS

• SLE or other autoimmune disorders

• Genetic markers: HLA-B8, HLA-DR2, HLA-DR3

• Race: Blacks, Hispanics, Asians, and Native Americans

Mechanism

Antiphospholipid syndrome is an autoimmune disease, in which “antiphospholipid antibodies” (anticardiolipin antibodies and lupus anticoagulant) react against proteins that bind to anionic phospholipids on plasma membranes. Like many autoimmune diseases, it is more common in women than in men. The exact cause is not known, but activation of the system of coagulation is evident. Clinically important antiphospholipid antibodies (those that arise as a result of the autoimmune process) are associated with thrombosis and vascular disease. The syndrome can be divided into primary (no underlying disease state) and secondary (in association with an underlying disease state) forms.

Anti-ApoH and a subset of anti-cardiolipin antibodies bind to ApoH, which in turn inhibits Protein C, a glycoprotein with regulatory function upon the common pathway of coagulation (by degradating activated factor V).

LAC antibodies bind to prothrombin, thus increasing its cleavage to thrombin, its active form.

In APS there are also antibodies binding to: Protein S, which is a co-factor of protein C. Thus, anti-protein S antibodies decrease protein C efficiency;

Annexin A5, which forms a shield around negatively-charged phospholipid molecules, thus reducing their availability for coagulation. Thus, anti-annexin A5 antibodies increase phospholipid-dependent coagulation steps.

The Lupus anticoagulant antibodies are those that show the closest association with thrombosis, those that target β₂glycoprotein 1 have a greater association with thrombosis than those that target prothrombin. Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (>40 GPLU or MPLU). Patients with both Lupus anticoagulant antibodies and moderate/high titre anticardiolipin antibodies show a greater risk of thrombosis than with one alone.

Diagnosis

Antiphospholipid syndrome is tested for in the laboratory using both liquid phase coagulation assays (lupus anticoagulant) and solid phase ELISA assays (anti-cardiolipin antibodies).

Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Presence of genetic thrombophilia may determine the need for anticoagulation therapy. Thus genetic thrombophilia screening can consist of:

• Further studies for Factor V Leiden variant and the prothrombin G20210A mutation, Factor VIII levels, MTHFR mutation.

• Levels of protein C, free and total protein S, Factor VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1)

The testing of antibodies to the possible individual targets of aPL such as β₂ glycoprotein 1 and antiphosphatidyl serine is currently under debate as testing for anticardiolipin appears to be currently sensitive and specific for diagnosis of APS even though cardiolipin is not considered an in vivo target for antiphospholipid antibodies.

Lupus anticoagulant

This is tested for by using a minimum of two coagulation tests that are phospholipid sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged APTT that does not correct in an 80:20 mixture with normal human plasma (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The APTT (plus 80:20 mix), dilute Russell’s viper venom time (DRVVT), the kaolin clotting time (KCT), dilute thromboplastin time (TDT/DTT) or prothrombin time (using a lupus sensitive thromboplastin) are the principal tests used for the detection of lupus anticoagulant. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion demonstrating persistent positivity to allow a diagnosis of antiphospholipid syndrome. This is to prevent patients with transient positive tests (due to infection etc.) being diagnosed as positive.

Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g.: Factor VIII). This is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. The lupus anticoagulant will inhibit all the contact activation pathway factors (Factor VIII, Factor IX, Factor XI and Factor XII). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iu/dl (35%) whereas a specific factor antibody will rarely give a result higher than 10 iu/dl (10%). Monitoring IV anticoagulant therapy by the APTT ratio is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of Factor Xa by antithrombin in the presence of heparin.

Anticardiolipin antibodies

These can be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test, which screens for the presence of β₂glycoprotein 1 dependent anticardiolipin antibodies (ACA).

A low platelet count and positivity for antibodies against β₂-glycoprotein 1 or phosphatidylserine may also be observed in a positive diagnosis.

Criteria

Classification with APS requires evidence of both one or more specific, documented clinical events (either a vascular thrombosis and/or adverse obstetric event) and the confirmed presence of a repeated aPL. The Sapporo APS classification criteria (1998, published in 1999) were replaced by the Sydney criteria in 2006. Based on the most recent criteria, classification with APS requires one clinical and one laboratory manifestation:

• Clinical:

• A documented episode of arterial, venous, or small vessel thrombosis — other than superficial venous thrombosis — in any tissue or organ by objective validated criteria with no significant evidence of inflammation in the vessel wall, and/or

• 1 or more unexplained deaths of a morphologically normal fetus (documented by ultrasound or direct examination of the fetus) at or beyond the 10th week of gestation and/or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded or at least 1 premature birth of a morphologically normal neonate before the 34th week of gestation due to eclampsia or severe pre-eclampsia according to standard definitions, or recognized features of placental insufficiency plus

• Laboratory:

• Anti-cardiolipin IgG and/or IgM measured by standardized, non-cofactor dependent ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (i.e., > 40 GPL or MPL, or > the 99th percentile) and/or

• Anti-β2 glycoprotein I IgG and/or IgM measured by standardized ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (> the 99th percentile) and/or

• Lupus anticoagulant detected on 2 occasions not less than 12 weeks apart according to the guidelines of the International Society of Thrombosis and Hemostasis.

There are 3 distinct APS disease entities: primary (the absence of any comorbidity), secondary (when there is a pre-existing autoimmune condition, most frequently systemic lupus erythematosus, SLE), and catastrophic (when there is simultaneous multi-organ failure with small vessel occlusion).

According to a 2006 consensus statement, it is advisable to classify APS into one of the following categories for research purposes:

• I: more than one laboratory criterion present in any combination;

• IIa: lupus anticoagulant present alone

• IIb: anti-cardiolipin IgG and/or IgM present alone in medium or high titers

• IIc: anti-β2 glycoprotein I IgG and/or IgM present alone in a titer greater than 99th percentile

The International Consensus Statement is commonly used for Catastrophic APS diagnosis.^[6] Based on this statement, Definite CAPS diagnosis requires:

• a) Vascular thrombosis in three or more organs or tissues and

• b) Development of manifestations simultaneously or in less than a week ‘and

• c) Evidence of small vessel thrombosis in at least one organ or tissue and

• d) Laboratory confirmation of the presence of aPL.

VDRL, which detects antibodies against syphilis, may have a false positive result in aPL-positive patients (aPL bind to the lipids in the test and make it come out positive), although the more specific test for syphilis, FTA-Abs, that use recombinant antigens will not have a false-positive result.

Treatment

Often, this disease is treated by giving aspirin to inhibit platelet activation, and/or warfarin as an anticoagulant. The goal of the prophylactic treatment with warfarin is to maintain the patient’s INR between 2.0 and 3.0. It is not usually done in patients who have had no thrombotic symptoms. During pregnancy, low molecular weight heparin and low-dose aspirin are used instead of warfarin because of warfarin’s teratogenicity. Women with recurrent miscarriage are often advised to take aspirin and to start low molecular weight heparin treatment after missing a menstrual cycle. In refractory cases plasmapheresis may be used.

Prognosis

The long-term prognosis for APS is determined mainly by recurrent thrombosis, which may occur in up to 29% of patients, sometimes despite antithrombotic therapy.

Sepsis. Sepsis (/ˈsɛpsɨs/; from the Greek σῆψις: the state of putrefaction and decay) is a potentially deadly medical

condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) caused by severe infection. Septicemia (also septicaemia or septicæmia [ˌsɛp.tə.ˈsi.miə]) is a related medical term referring to the presence of pathogenic organisms in the bloodstream, leading to sepsis.The term has not been sharply defined. It has been inconsistently used in the past by medical professionals, for example as a synonym of bacteremia, causing some confusion.

Sepsis is caused by the immune system’s response to a serious infection, most commonly bacteria, but also fungi, viruses, and parasites in the blood, urinary tract, lungs, skin, or other tissues. Sepsis can be thought of as falling within a continuum from infection to multiple organ dysfunction syndrome.

Common symptoms of sepsis include those related to a specific infection, but usually accompanied by high fevers, hot, flushed skin, elevated heart rate, hyperventilation, altered mental status, swelling, and low blood pressure. In the very young and elderly, or in people with weakened immune systems, the pattern of symptoms may be atypical, with hypothermia and without an easily localizable infection.  Sepsis causes millions of deaths globally each year.

Sepsis is usually treated with intravenous fluids and antibiotics. If fluid replacement isn’t sufficient to maintain blood pressure, vasopressors can be used. Mechanical ventilation and dialysis may be needed to support the function of the lungs and kidneys, respectively. To guide therapy, a central venous catheter and an arterial catheter may be placed; measurement of other hemodynamic variables (such as cardiac output, mixed venous oxygen saturation or stroke volume variation) may also be used. Sepsis patients require preventive measures for deep vein thrombosis, stress ulcers and pressure ulcers, unless other conditions prevent this. Some might benefit from tight control of blood sugar levels with insulin (targeting stress hyperglycemia). The use of corticosteroids is controversial.^[9] Activated drotrecogin alfa (recombinant activated protein C), originally marketed for severe sepsis, has not been found to be helpful, and has recently been withdrawn from sale.

Signs and symptomsIn addition to symptoms related to the provoking infection, sepsis is frequently associated with either fever or hypothermia, rapid breathing, elevated heart rate, confusion, and edema. Early signs are elevated heart rate, decreased urination, and elevated blood sugar, while signs of established sepsis are confusion, metabolic acidosis with compensatory respiratory alkalosis (which can manifest as faster breathing), low blood pressure, decreased systemic vascular resistance, higher cardiac output, and dysfunctions of blood coagulation.

Sepsis may also lead to a drop in blood pressure, resulting in shock. This may result in light-headedness. Bruising or intense bleeding may also occur.

Cause

The most common primary sources of infection resulting in sepsis are the lungs, the abdomen and the urinary tract. No source is found in one third of cases.The infectious agents are usually bacteria but can also be fungi and viruses. While gram-negative bacteria were previously the most common cause of sepsis, in the last decade, gram-positive bacteria, most commonly staphylococci, are thought to cause more than 50% of cases of sepsis.

Diagnosis

Systemic inflammatory response syndrome
Finding	Value
Temperature	<36 °C (96.8 °F) or >38 °C (100.4 °F)
Heart rate	>90/min
Respiratory rate	>20/min or PaCO2<32 mmHg (4.3 kPa)
WBC	<4×109/L (<4000/mm³), >12×109/L (>12,000/mm³), or 10% bands

In those with sepsis it is recommended that blood cultures be drawn before antibiotics are given.

Definitions

According to the American College of Chest Physicians and the Society of Critical Care Medicine, there are different levels of sepsis:

• Systemic inflammatory response syndrome (SIRS) is the presence of two or more of the following: abnormal body temperature, heart rate, respiratory rate or blood gas, and white blood cell count.

• Sepsis is defined as SIRS in response to an infectious process.

• Severe sepsis is defined as sepsis with sepsis-induced organ dysfunction or tissue hypoperfusion (manifesting as hypotension, elevated lactate, or decreased urine output.

• Septic shock is severe sepsis plus persistently low blood pressure following the administration of intravenous fluids.

Infection

Infection can be suspected or proven (by culture, stain, or polymerase chain reaction (PCR)), or a clinical syndrome pathognomonic for infection. Specific evidence for infection includes WBCs iormally sterile fluid (such as urine or cerebrospinal fluid (CSF)); evidence of a perforated viscus (free air on abdominal x-ray or CT scan; signs of acute peritonitis); abnormal chest x-ray (CXR) consistent with pneumonia (with focal opacification); or petechiae, purpura, or purpura fulminans.

End-organ dysfunction

Examples of end-organ dysfunction include the following:

• Lungs:acute lung injury (ALI) (PaO₂/FiO₂ < 300) or acute respiratory distress syndrome (ARDS) (PaO₂/FiO₂ < 200)

• Brain: encephalopathy symptoms: agitation, confusion, coma; cause: ischemia, hemorrhage, microthrombi, microabscesses, multifocal necrotizing leukoencephalopathy

• Liver: disruption of protein synthetic function: manifests acutely as progressive coagulopathy due to inability to synthesize clotting factors, disruption of metabolic functions: manifests as cessation of bilirubin metabolism, resulting in elevated unconjugated serum bilirubin levels

• Kidney: oliguria and anuria, electrolyte abnormalities, volume overload

• Heart: systolic and diastolic heart failure, likely due to cytokines that depress myocyte function, cellular damage, manifest as a troponin leak (although not necessarily ischemic iature)

More specific definitions of end-organ dysfunction exist for SIRS in pediatrics.^[19]

• Cardiovascular dysfunction (after fluid resuscitation with at least 40 ml/kg of crystalloid)

• hypotension with blood pressure < 5th percentile for age or systolic blood pressure < 2 standard deviations below normal for age, OR

• vasopressor requirement, OR

• two of the following criteria:

• unexplained metabolic acidosis with base deficit > 5 mEq/L

• lactic acidosis: serum lactate 2 times the upper limit of normal

• oliguria (urine output < 0.5 ml/kg/hr)

• prolonged capillary refill > 5 seconds

• core to peripheral temperature difference > 3°C

• Respiratory dysfunction (in the absence of cyanotic heart disease or known chronic lung disease)

• the ratio of the arterial partial-pressure of oxygen to the fraction of oxygen in the gases inspired (PaO₂/FiO₂) < 300 (the definition of acute lung injury), OR

• arterial partial-pressure of carbon dioxide (PaCO₂) > 65 torr (20 mmHg) over baseline PaCO₂ (evidence of hypercapnic respiratory failure), OR

• supplemental oxygen requirement of greater than FiO₂ 0.5 to maintain oxygen saturation ≥ 92%

• Neurologic dysfunction

• Glasgow Coma Score (GCS) ≤ 11, OR

• altered mental status with drop in GCS of 3 or more points in a patient with developmental delay/mental retardation

• Hematologic dysfunction

• platelet count < 80,000/mm³ or 50% drop from maximum in chronically thrombocytopenic patients, OR

• international normalized ratio (INR) > 2

• Disseminated intravascular coagulation

• Renal dysfunction

• serum creatinine ≥ 2 times the upper limit of normal for age or 2-fold increase in baseline creatinine in patients with chronic kidney disease

• Hepatic dysfunction (only applicable to infants > 1 month)

• total serum bilirubin ≥ 4 mg/dl, OR

• alanine aminotransferase (ALT) ≥ 2 times the upper limit of normal

Consensus definitions, however, continue to evolve, with the latest expanding the list of signs and symptoms of sepsis to reflect clinical bedside experience.

Differential diagnosis

The differential diagnosis for sepsis is broad and includes those conditions that can cause the systemic signs of SIRS: alcohol withdrawal, pulmonary embolus, thyrotoxicosis, anaphylaxis, adrenal insufficiency, and neurogenic shock.

Neonatal sepsis

In common clinical usage, neonatal sepsis specifically refers to the presence of a bacterial blood stream infection (BSI), such as meningitis, pneumonia, pyelonephritis, or gastroenteritis, in the setting of fever. Criteria with regards to hemodynamic compromise or respiratory failure are not useful clinically because these symptoms often do not arise ieonates until death is imminent and unpreventable.

Pathophysiology

Sepsis is caused by a combination of factors related to the invading organism(s) and the host (pre-disposing illnesses, genetics, and immune system).

Microbial factors

A bacteria’s capsule (for example, in certain strains of Streptococcus pneumoniae), can allow it to evade phagocytosis, while pili of some strains of E. Coli can allow this bacterium to adhere to the epithelium of the kidneys. Sepsis caused by gram negative bacteria is thought to be largely due to the host’s response to lipopolysaccharides, also called LPS or endotoxin, in the cell wall, while gram positive bacteria are more likely to cause sepsis by their release of exotoxins. Some exotoxins can quickly lead to a rapid release of cytokines by acting as superantigens, which can simultaneously bind MHC and the T-cell receptor.

Host factors

Severe sepsis occurs when sepsis leads to organ dysfunction, such as pulmonary dysfunction, coagulation or other blood abnormalities, decreased urine production, or altered mental status. If the organ dysfunction of severe sepsis is associated with low blood pressure (hypotension), or insufficient blood flow (hypoperfusion) to one or more organs (causing, for example, lactic acidosis), this is septic shock.

Sepsis can lead to multiple organ dysfunction syndrome (MODS) (formerly known as multiple organ failure), and death. Organ dysfunction results from local changes in blood flow, from sepsis-induced hypotension (< 90 mmHg or a reduction of ≥ 40 mmHg from baseline) and from diffuse intravascular coagulation, among other things.

Bacteremia is the presence of viable bacteria in the bloodstream. Likewise, the terms viremia and fungemia simply refer to viruses and fungi in the bloodstream. These terms say nothing about the consequences this has on the body. For example, bacteria can be introduced into the bloodstream during toothbrushing. This form of bacteremia almost never causes problems iormal individuals. However, bacteremia associated with certain dental procedures can cause bacterial infection of the heart valves (known as endocarditis) in high-risk patients. Conversely, a systemic inflammatory response syndrome can occur in patients without the presence of infection, for example in those with burns, polytrauma, or the initial state in pancreatitis and chemical pneumonitis.

Management

The therapy of sepsis rests on intravenous fluids, antibiotics, surgical drainage of infected fluid collections, and appropriate support for organ dysfunction. This may include hemodialysis in kidney failure, mechanical ventilation in pulmonary dysfunction, transfusion of blood products, and drug and fluid therapy for circulatory failure. Ensuring adequate nutrition—preferably by enteral feeding, but if necessary by parenteral nutrition—is important during prolonged illness.

In those with high blood sugar levels, insulin to bring it down to 7.8-10 mmol/L (140-180 mg/dL) is recommended with lower levels potentially worsening outcomes. Medication to prevent deep vein thrombosis and gastric ulcers may also be used.

Antibiotics

In severe sepsis, broad spectrum antibiotics are recommended within 1 hour of making the diagnosis. For every hour delay in the administration there is an associated 6% rise in mortality. Duration of treatment is typically 7-10 days with the type of antibiotic used directed by the results of cultures.

Early goal directed therapy

Early goal directed therapy (EGDT) is an approach to the management of severe sepsis during the initial 6 hours after diagnosis. A step-wise approach should be used, with the physiologic goal of optimizing cardiac preload, afterload, and contractility. It has been found to reduce mortality in those with sepsis.

Urine output is also monitored, with a minimum goal of 0.5 ml/kg/h. In the original trial, mortality was cut from 46.5% to 30.5%. An appropriate decrease in serum lactate however may be equivalent to SvO2 and easier to obtain.

Intravenous fluids

In EGDT, fluids are titrated in response to heart rate, blood pressure, and urine output; restoring large fluid deficits can require 6 to 10L of crystalloids. In cases where a central venous catheter is used to measure blood pressures dynamically, fluids should be administered until the central venous pressure (CVP) reaches 8–12 cm of water (or 10–15 cm of water in mechanically ventilated patients). Once these goals are met, the mixed venous oxygen saturation (SvO2), i.e., the oxygen saturation of venous blood as it returns to the heart as measured at the vena cava, is optimized. If the SvO2 is less than 70%, blood is given to reach a hemoglobin of 10 g/dl and then inotropes are added until the SvO2 is optimized.

Vasopressors

Once the person has been sufficiently fluid resuscitated if the mean arterial pressure is not greater than 65 mmHg vasopressors are recommended. While current recommendations suggest either norepinephrine (noradrenaline) or dopamine,the former appears safer. If a single pressor is not sufficient in improving the blood pressure, epinephrine (adrenaline) may be added in.

Ventilation

Elective tracheal intubation and mechanical ventilation may be performed to reduce oxygen demand if the SvO2 remains low despite optimization of hemodynamics. Etomidate is not recommended as a medication to help with intubation in this situation due to concerns of adrenal insufficiency and increased mortality.

Steroids

The use of steroids in sepsis is controversial.During critical illness, a state of adrenal insufficiency and tissue resistance to corticosteroids may occur. This has been termed critical illness–related corticosteroid insufficiency. Treatment with corticosteroids might be most beneficial in those with septic shock and early severe acute respiratory distress syndrome (ARDS), whereas its role in others such as those with pancreatitis or severe pneumonia is unclear. However, the exact way of determining corticosteroid insufficiency remains problematic. It should be suspected in those poorly responding to resuscitation with fluids and vasopressors. ACTH stimulation testing is not recommended to confirm the diagnosis. The method of cessation of glucocorticoid drugs is variable, and it is unclear whether they should be weaned or simply stopped abruptly.

Activated protein C

Recombinant activated protein C (drotrecogin alpha) was originally introduced for severe sepsis (as identified by a high APACHE II score), where it was thought to confer a survival benefit. However, subsequent studies showed that it increased adverse events and did not decrease mortality. It was removed from sale in 2011.

Neonates

Neonatal sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent. If there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative.

Prognosis

Approximately 20–35% of people with severe sepsis and 30–70% of people with septic shock die. Lactate is a useful method of determining prognosis with those who have a level greater than 4 mmol/L having a mortality of 40% and those with a level of less than 2 mmol/L have a mortality of less than 15%.

There are a number of prognostic stratification systems such as APACHE II and Mortality in Emergency Department Sepsis. APACHE II factors in the person’s age, underlying condition, and various physiologic variables can yield estimates of the risk of dying of severe sepsis. Of the individual covariates, the severity of underlying disease most strongly influences the risk of death. Septic shock is also a strong predictor of short- and long-term mortality. Case-fatality rates are similar for culture-positive and culture-negative severe sepsis. The Mortality in Emergency Department Sepsis (MEDS) score is simpler and useful in the emergency department environment.

Some people may experience severe long-term cognitive decline following an episode of severe sepsis, but the absence of baseline neuropsychological data in most sepsis patients makes the incidence of this difficult to quantify or to study.

Epidemiology

Sepsis causes millions of deaths globally each year. In the United States sepsis affects approximately 3 in 1000 people^[16] and severe sepsis contributes to more than 200,000 deaths per year.  Due to its rarely being reported as a primary diagnosis (often being a complication of cancer or other illnesses), the incidence, mortality, and morbidity rates are likely underestimated. It is the second-leading cause of death ion-coronary intensive care unit (ICU) patients, and the tenth-most-common cause of death overall according to data from the (the first being heart disease). Children under 12 months and elderly have the highest incidence of severe sepsis. It occurs in 1–2% of all hospitalizations and accounts for as much as 25% of ICU bed utilization.

Giant-cell arteritis (GCA). Giant-cell arteritis (GCA or temporal arteritis or cranial arteritis) or Horton disease is an inflammatory disease of blood vessels most commonly involving large and medium arteries of the head, predominantly the branches of the external carotid artery. It is a form of vasculitis.

The name (giant cell arteritis) reflects the type of inflammatory cell involved as seen on a biopsy.

The terms “giant-cell arteritis” and “temporal arteritis” are sometimes used interchangeably, because of the frequent involvement of the temporal artery. However, it can involve other large vessels (such as the aorta in “giant-cell aortitis”). Giant-cell arteritis of the temporal artery is referred to as “temporal arteritis,” and is also known as “cranial arteritis” and “Horton’s disease.”

Signs and symptoms

It is more common in women than in men by a ratio of 2:1 and more common in those of Northern European descent, as well as those residing at higher latitudes. The mean age of onset is >55 years, and it is rare in those less than 55 years of age.

People present with:

• bruits

• fever

• headache

• tenderness and sensitivity on the scalp

• jaw claudication (pain in jaw when chewing)

• tongue claudication (pain in tongue when chewing) and necrosis

• reduced visual acuity (blurred vision)

• acute visual loss (sudden blindness)

• diplopia (double vision)

• acute tinnitus (ringing in the ears)

• polymyalgia rheumatica (in 50%)

The inflammation may affect blood supply to the eye and blurred vision or sudden blindness may occur. In 76% of cases involving the eye, the ophthalmic artery is involved causing arteritic anterior ischemic optic neuropathy. Loss of vision in both eyes may occur very abruptly and this disease is therefore a medical emergency.

Associated conditions

The disorder may coexist (in one quarter of cases) with polymyalgia rheumatica (PMR), which is characterized by sudden onset of pain and stiffness in muscles (pelvis, shoulder) of the body and is seen in the elderly. GCA and PMR are so closely linked that they are often considered to be different manifestations of the same disease process. Other diseases related with temporal arteritis are systemic lupus erythematosus, rheumatoid arthritis, and severe infections.

Giant-cell arteritis can involve branches of the aorta as well leading to aortic aneurysm. For this reason patients should be followed with serial chest X-rays

Diagnosis

Physical exam

• Palpation of the head reveals prominent temporal arteries with or without pulsation.

• The temporal area may be tender.

• Decreased pulses may be found throughout the body

• Evidence of ischemia may be noted on fundal exam.

Laboratory tests

• LFTs, liver function tests, are abnormal particularly raised ALP- alkaline phosphatase

• Erythrocyte sedimentation rate, an inflammatory marker, >60 mm/hour (normal 1–40 mm/hour).

• C-reactive protein, another inflammatory marker, is also commonly elevated.

• Platelets may also be elevated.

Biopsy

Histopathology of giant cell vasculitis in a cerebral artery. Elastica-stain.

The gold standard for diagnosing temporal arteritis is biopsy, which involves removing a small part of the vessel and examining it microscopically for giant cells infiltrating the tissue. Since the blood vessels are involved in a patchy pattern, there may be unaffected areas on the vessel and the biopsy might have been taken from these parts. Unilateral biopsy of a 1.5–3 cm length is 85-90% sensitive (1 cm is the minimum). So, a negative result does not definitely rule out the diagnosis. Thus, currently biopsy is only considered confirmatory for the clinical diagnosis, or one of diagnostic criteria

Imaging studies

Radiological examination of the temporal artery with ultrasound yields a halo sign. Contrast enhanced brain MRI and CT is generally negative in this disorder. Recent studies have shown that 3T MRI using super high resolution imaging and contrast injection caon-invasively diagnose this disorder with high specificity and sensitivity.

Treatment

Corticosteroids, typically high-dose prednisone (1 mg/kg/day), must be started as soon as the diagnosis is suspected (even before the diagnosis is confirmed by biopsy) to prevent irreversible blindness secondary to ophthalmic artery occlusion. Steroids do not prevent the diagnosis from later being confirmed by biopsy, although certain changes in the histology may be observed towards the end of the first week of treatment and are more difficult to identify after a couple of months.^[10] The dose of prednisone is lowered after 2–4 weeks, and slowly tapered over 9–12 months. Tapering may require two or more years. Oral steroids are at least as effective as intravenous steroids,^[11] except in the treatment of acute visual loss where intravenous steroids appear to offer significant benefit over oral steroids.

Hernia. A hernia is the protrusion of an organ or the fascia of an organ through the wall of the cavity that normally contains it.There are different kinds of hernia, each requiring a specific management or treatment. Signs and symptoms

By far the most common hernias develop in the abdomen, when a weakness in the abdominal wall evolves into a localized hole, or “defect”, through which adipose tissue, or abdominal organs covered with peritoneum, may protrude. Another common hernia involves the spinal discs and causes sciatica. A hiatal hernia occurs when the stomach protrudes into the mediastinum through the esophageal opening in the diaphragm.

Hernias may or may not present with either pain at the site, a visible or palpable lump, or in some cases more vague symptoms resulting from pressure on an organ which has become “stuck” in the hernia, sometimes leading to organ dysfunction. Fatty tissue usually enters a hernia first, but it may be followed or accompanied by an organ.

Symptoms may or may not be present in some inguinal hernias, while in some other hernias they are. Symptoms and signs vary depending on the type of hernia. In the case of reducible hernias, a bulge in the groin or in another abdominal area can often be seen and felt. When standing, such a bulge becomes more obvious. Besides the bulge, other symptoms include pain in the groin that may also include a heavy or dragging sensation, and in men, there is sometimes pain and swelling in the scrotum around the testicular area.

Irreducible abdominal hernias or incarcerated hernias may be painful, but their most relevant symptom is that they cannot return to the abdominal cavity when pushed in. They may be chronic, although painless, and can lead to strangulation. Strangulated hernias are always painful and pain is followed by tenderness. Nausea, vomiting, or fever may occur in these cases due to bowel obstruction. Also, the hernia bulge in this case may turn red, purple or dark and pink.

In the diagnosis of abdominal hernias, imaging is the principal means of detecting internal diaphragmatic and other nonpalpable or unsuspected hernias. Multidetector CT (MDCT) can show with precision the anatomic site of the hernia sac, the contents of the sac, and any complications. MDCT also offers clear detail of the abdominal wall allowing wall hernias to be identified accurately.^[4]

Causes

Most of the time, hernias develop when pressure in the compartment of the residing organ is increased, and the boundary is weak or weakened.

• Weakening of containing membranes or muscles is usually congenital (which explains part of the tendency of hernias to run in families), and increases with age (for example, degeneration of the annulus fibrosus of the intervertebral disc), but it may be on the basis of other illnesses, such as Ehlers-Danlos syndrome or Marfan syndrome, stretching of muscles during pregnancy, losing weight in obese people, etc., or because of scars from previous surgery.

• Many conditions chronically increase intra-abdominal pressure, (pregnancy, ascites, COPD, dyschezia, benign prostatic hypertrophy) and hence abdominal hernias are very frequent. Increased intracranial pressure can cause parts of the brain to herniate through narrowed portions of the cranial cavity or through the foramen magnum. Increased pressure on the intervertebral discs, as produced by heavy lifting or lifting with improper technique, increases the risk of herniation.

Causes of hiatal hernia vary depending on each individual. Among the multiple causes, however, are the mechanical causes which include: poison, improper heavy weight lifting, hard coughing bouts, sharp blows to the abdomen, tight clothing and incorrect posture.

Furthermore, conditions that increase the pressure of the abdominal cavity may also cause hernias or worsen the existing ones. Some examples would be: obesity, straining during a bowel movement or urination, chronic lung disease, and also, fluid in the abdominal cavity.

Also, if muscles are weakened due to poor nutrition, smoking, and overexertion, hernias are more likely to occur.

The physiological school of thought contends that in the case of inguinal hernia, the above mentioned are only an anatomical symptom of the underlying physiological cause. They contend that the risk of hernia is due to a physiological difference between patients who suffer hernia and those who do not, namely the presence of aponeurotic extensions from the transversus abdominis aponeurotic arch.^[7]

Diagnosis

Inguinal

By far the most common hernias (up to 75% of all abdominal hernias) are the so-called inguinal hernias. Inguinal hernias are further divided into the more common indirect inguinal hernia (2/3, depicted here), in which the inguinal canal is entered via a congenital weakness at its entrance (the internal inguinal ring), and the direct inguinal hernia type (1/3), where the hernia contents push through a weak spot in the back wall of the inguinal canal. Inguinal hernias are the most common type of hernia in both men and women. In some selected cases, they may require surgery.

Femoral

Main article: femoral hernia

Femoral hernias occur just below the inguinal ligament, when abdominal contents pass into the weak area at the posterior wall of the femoral canal. They can be hard to distinguish from the inguinal type (especially when ascending cephalad): however, they generally appear more rounded, and, in contrast to inguinal hernias, there is a strong female preponderance in femoral hernias. The incidence of strangulation in femoral hernias is high. Repair techniques are similar for femoral and inguinal hernia.

Umbilical

Main article: umbilical hernia

They involve protrusion of intraabdominal contents through a weakness at the site of passage of the umbilical cord through the abdominal wall. These hernias often resolve spontaneously. Umbilical hernias in adults are largely acquired, and are more frequent in obese or pregnant women. Abnormal decussation of fibers at the linea alba may contribute.

Incisional

Main article: incisional hernia

An incisional hernia occurs when the defect is the result of an incompletely healed surgical wound. When these occur in median laparotomy incisions in the linea alba, they are termed ventral hernias. These can be the most frustrating and difficult to treat, as the repair utilizes already attenuated tissue.

Diaphragmatic

Main article: diaphragmatic hernia

 

Higher in the abdomen, an (internal) “diaphragmatic hernia” results when part of the stomach or intestine protrudes into the chest cavity through a defect in the diaphragm.

A hiatus hernia is a particular variant of this type, in which the normal passageway through which the esophagus meets the stomach (esophageal hiatus) serves as a functional “defect”, allowing part of the stomach to (periodically) “herniate” into the chest. Hiatus hernias may be either “sliding“, in which the gastroesophageal junction itself slides through the defect into the chest, or non-sliding (also known as para-esophageal), in which case the junction remains fixed while another portion of the stomach moves up through the defect. Non-sliding or para-esophageal hernias can be dangerous as they may allow the stomach to rotate and obstruct. Repair is usually advised.

A congenital diaphragmatic hernia is a distinct problem, occurring in up to 1 in 2000 births, and requiring pediatric surgery. Intestinal organs may herniate through several parts of the diaphragm, posterolateral (in Bochdalek’s triangle, resulting in Bochdalek’s hernia), or anteromedial-retrosternal (in the cleft of Larrey/Morgagni’s foramen, resulting in Morgagni-Larrey hernia, or Morgagni’s hernia).

Other hernias

Since many organs or parts of organs can herniate through many orifices, it is very difficult to give an exhaustive list of hernias, with all synonyms and eponyms. The above article deals mostly with “visceral hernias”, where the herniating tissue arises within the abdominal cavity. Other hernia types and unusual types of visceral hernias are listed below, in alphabetical order:

• Amyand’s hernia: containing the appendix vermiformis within the hernia sac

• Busse’s Hernia: a testicle within the hernia sac

• Cooper’s hernia: a femoral hernia with two sacs, the first being in the femoral canal, and the second passing through a defect in the superficial fascia and appearing almost immediately beneath the skin.

• Epigastric hernia: a hernia through the linea alba above the umbilicus.

• Hiatal hernia: a hernia due to “short oesophagus” — insufficient elongation — stomach is displaced into the thorax

• Littre’s hernia: a hernia involving a Meckel’s diverticulum. It is named after the French anatomist Alexis Littré (1658–1726).

• Lumbar hernia (Bleichner’s Hernia): a hernia in the lumbar region (not to be confused with a lumbar disc hernia), contains the following entities:

• Petit’s hernia: a hernia through Petit’s triangle (inferior lumbar triangle). It is named after French surgeon Jean Louis Petit (1674–1750).

• Grynfeltt’s hernia: a hernia through Grynfeltt-Lesshaft triangle (superior lumbar triangle). It is named after physician Joseph Grynfeltt (1840–1913).

• Maydl’s hernia: two adjacent loops of small intestine are within a hernial sac with a tight neck. The intervening portion of bowel within the abdomen is deprived of its blood supply and eventually becomes necrotic.

• Morgagni hernia: a type of hernia where abdominal contents pass into the thorax through a weakness in the diaphragm

• Obturator hernia: hernia through obturator canal

• Pantaloon hernia (Saddle Bag hernia): a combined direct and indirect hernia, when the hernial sac protrudes on either side of the inferior epigastric vessels

• Paraesophageal hernia

• Paraumbilical hernia: a type of umbilical hernia occurring in adults

• Perineal hernia: a perineal hernia protrudes through the muscles and fascia of the perineal floor. It may be primary but usually is acquired following perineal prostatectomy, abdominoperineal resection of the rectum, or pelvic exenteration.

• Properitoneal hernia: rare hernia located directly above the peritoneum, for example, when part of an inguinal hernia projects from the deep inguinal ring to the preperitoneal space.

• Richter’s hernia: a hernia involving only one sidewall of the bowel, which can result in bowel strangulation leading to perforation through ischaemia without causing bowel obstruction or any of its warning signs. It is named after German surgeon August Gottlieb Richter (1742–1812).

• Sliding hernia: occurs when an organ drags along part of the peritoneum, or, in other words, the organ is part of the hernia sac. The colon and the urinary bladder are often involved. The term also frequently refers to sliding hernias of the stomach.

• Sciatic hernia: this hernia in the greater sciatic foramen most commonly presents as an uncomfortable mass in the gluteal area. Bowel obstruction may also occur. This type of hernia is only a rare cause of sciatic neuralgia.

• Spigelian hernia, also known as spontaneous lateral ventral hernia

• Sports hernia: a hernia characterized by chronic groin pain in athletes and a dilated superficial inguinal ring.

• Velpeau hernia: a hernia in the groin in front of the femoral blood vessels

Characteristics

Hernias can be classified according to their anatomical location:

Examples include:

• abdominal hernias

• diaphragmatic hernias and hiatal hernias (for example, paraesophageal hernia of the stomach)

• pelvic hernias, for example, obturator hernia

• anal hernias

• hernias of the nucleus pulposus of the intervertebral discs

• intracranial hernias

• Spigelian hernia ^[8]

Each of the above hernias may be characterized by several aspects:

• congenital or acquired: congenital hernias occur prenatally or in the first year(s) of life, and are caused by a congenital defect, whereas acquired hernias develop later on in life. However, this may be on the basis of a locus minoris resistantiae (Lat. place of least resistance) that is congenital, but only becomes symptomatic later in life, when degeneration and increased stress (for example, increased abdominal pressure from coughing in COPD) provoke the hernia.

• complete or incomplete: for example, the stomach may partially or completely herniate into the chest.

• internal or external: external ones herniate to the outside world, whereas internal hernias protrude from their normal compartment to another (for example, mesenteric hernias).

• intraparietal hernia: hernia that does not reach all the way to the subcutis, but only to the musculoaponeurotic layer. An example is a Spigelian hernia. Intraparietal hernias may produce less obvious bulging, and may be less easily detected on clinical examination.

• bilateral: in this case, simultaneous repair may be considered, sometimes even with a giant prosthetic reinforcement.

• irreducible: the hernial contents cannot be returned to their normal site with simple manipulation.

If irreducible, hernias can develop several complications (hence, they can be complicated or uncomplicated):

• strangulation: pressure on the hernial contents may compromise blood supply (especially veins, with their low pressure, are sensitive, and venous congestion often results) and cause ischemia, and later necrosis and gangrene, which may become fatal.

• obstruction: for example, when a part of the bowel herniates, bowel contents cao longer pass the obstruction. This results in cramps, and later on vomiting, ileus, absence of flatus and absence of defecation.

• dysfunction: another complication arises when the herniated organ itself, or surrounding organs, start to malfunction (for example, sliding hernia of the stomach causing heartburn, lumbar disc hernia causing sciatic nerve pain, etc.).

Treatment

For a hernia like inguinal hernia, surgery is no longer recommended in most cases. However, it is in few cases advisable to repair some other kinds of hernias, in order to prevent complications such as organ dysfunction, gangrene and multiple organ dysfunction syndrome. Most abdominal hernias can be surgically repaired, but surgery often has complications, such as chronic groin pain. Time needed for recovery after treatment is greatly reduced if hernias are operated on laparoscopically, the minimally invasive operation most commonly used today. Uncomplicated hernias are principally repaired by pushing back, or “reducing”, the herniated tissue, and then mending the weakness in muscle tissue (an operation called herniorrhaphy). If complications have occurred, the surgeon will check the viability of the herniated organ, and resect it if necessary.

Muscle reinforcement techniques often involve synthetic materials (a mesh prosthesis). The mesh is placed either over the defect (anterior repair) or under the defect (posterior repair). At times staples are used to keep the mesh in place. These mesh repair methods are often called “tension free” repairs because, unlike some suture methods (e.g. Shouldice), muscle is not pulled together under tension. However, this widely used terminology is misleading, as there also exists many tension-free suture methods that do not use mesh (e.g. Desarda, Guarnieri, Lipton-Estrin…).

Evidence suggests that tension-free methods (with or without mesh) often have lower percentage of recurrences and the fastest recovery period compared to tension suture methods. However, among other possible complications, prosthetic mesh usage seems to have a higher incidence of chronic pain and, sometimes, infection.

One study attempted to identify the factors related to mesh infections and found that compromised immune systems (such as diabetes) was a factor. Mesh has also become the subject of recalls and class action lawsuits.

Laparoscopic surgery is also referred to as “minimally invasive” surgery, which requires one or more small incisions for the camera and instruments to be inserted, as opposed to traditional “open” or “microscopic” surgery, which requires an incision large enough for the surgeon’s hands to be inserted into the patient. The term microscopic surgery refers to the magnifying devices used during open surgery.

Many patients are managed through day surgery centers, and are able to return to work within a week or two, while intensive activities are prohibited for a longer period. Patients who have their hernias repaired with mesh often recover in a number of days, though pain can last longer, and often forever. Surgical complications have been estimated to be more than 20 percent. They include chronic pain, surgical site infections, nerve and blood vessel injuries, injury to nearby organs, and hernia recurrence.

Due to surgical risks, mainly chronic pain risk, the use of external devices to maintain reduction of the hernia without repairing the underlying defect (such as hernia trusses, trunks, belts, etc.) are often used. In particular, we can mention uncomplicated incisional hernias that arise shortly after the operation (should only be operated after a few months), or inoperable patients. There have been known cases where hiatal and esophageal hernias have shown signs of improvements after the patient stopped producing stress on the affected area by fasting or parenteral nutrition. It is essential that the hernia not be further irritated by carrying out strenuous labour.

Complications

Complications may arise post-operation, including rejection of the mesh that is used to repair the hernia. In the event of a mesh rejection, the mesh will very likely need to be removed. Mesh rejection can be detected by obvious, sometimes localised swelling and pain around the mesh area. Continuous discharge from the scar is likely for a while after the mesh has been removed.

A surgically treated hernia can lead to complications, while an untreated hernia may be complicated by:

• Inflammation

• Irreducibility

• Obstruction of any lumen, such as bowel obstruction in intestinal hernias

• Strangulation

• Hydrocele of the hernial sac

• Haemorrhage

• Autoimmune problems

• Incarceration, which is where it cannot be reduced, or pushed back into place, at least not without very much external effort. In intestinal hernias, this also substantially increases the risk of bowel obstruction and strangulation.

• Volvulus.

Cardiovascular Diseases Glossary

 

REFERENCES:

1.     Bridget B. Kelly; Institute of Medicine; Fuster, Valentin (2010). Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. Washington, D.C: National Academies Press. ISBN 0-309-14774-3.

2.     Hooper, L; Summerbell, CD; Thompson, R; Sills, D; Roberts, FG; Moore, HJ; Davey Smith, G (2012 May 16). “Reduced or modified dietary fat for preventing cardiovascular disease.“. Cochrane database of systematic reviews (Online) 5: CD002137. doi:10.1002/14651858.CD002137.pub3. PMID 22592684

3.     Mendis, S.; Puska, P.; Norrving, B.(editors) (2011), Global Atlas on cardiovascular disease prevention and control, ISBN 978-92-4-156437-3

4.     Spence JD (2006). “Technology Insight: ultrasound measurement of carotid plaque–patient management, genetic research, and therapy evaluation”. Nat Clin Pract Neurol 2 (11): 611–9. doi:10.1038/ncpneuro0324. PMID 17057748

5.     Venuraju SM, Yerramasu A, Corder R, Lahiri A (May 2010). “Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity”. J. Am. Coll. Cardiol. 55 (19): 2049–61.