Cell injury and death in thrombosis

Cell Injury & Death, Thrombosis & Embolism, Cell Function in relation to Inflammation, Causes & Course of Inflammation

The human body may pose natural responses to external and internal influences, such as trauma, infection, poisoning, and loss of blood flow, autoimmunity, or errors of development. Pathology is looking at the way in which the body's responses to injury, while evolved to protect health, can also contribute in some ways to disease processes. Human cells may respond to injury and stress by specific mechanisms and may result in CELL INJURY or CELL DEATH. Please describe cell injury and cell death respectively.

Cellular injury occurs when a cell is unable to maintain its steady state or homeostasis. Normal and healthy cells live in a state of equilibrium with their external environment and this helps them to perform their routine functions. When the cell is unable to maintain its homeostasis in the event of an injurious stimuli, then the cells die or recover. Some examples of stimuli that can interfere with the normal functioning of the cell include exposure to toxins, lack of oxygen or hypoxia, infections, immunologic reactions and lack of proper nutrition.

The exact nature of the cellular injury including its severity is determined by the type of cell and the stimuli that is affecting it. Also, the overall state of health and the nutritional intake of individuals vary and this has an impact in the degree of severity of the cells. In general, cellular injury can be broadly classified into three kinds and they are Hypoxic injury, chemical injury and injury due to the presence of free radicals. Cobb, Hotchkiss, Karl & Butchman (1996) further explain the causes of cell injury as:

Physical

Ionizing Radiation

Temperature

Mechanical Trauma

Biological

Enzymes

Cytokines

Viral infections

Cell mediation

Chemical

Drugs

Posions

Critical Substrate Deficiency

Oxygen

Glucose

Hypoxic Injury

One of the most common forms of cellular injury is the Hypoxic injury and it occurs because of decreased levels of oxygen to the cells. There are many reasons for this decrease and this includes reduced levels of oxygen in the air, slower or reduced production of red blood cells and compromised respiratory system. Ischemia is a common cause of hypoxia and it occurs because the flow of blood in the arteries is blocked by blood clots. It can also be caused due to respiratory failures and the inability of the blood to carry oxygen due to diseases such as anemia.

Free Radicals

Free radicals are those atoms with an odd number of electrons and this makes them unstable and highly reactive. They are formed when the oxygen in the air reacts to certain drugs, toxins or molecules. They result in a chain reaction due to interactions with stable molecules such as protein, lipids and nucleic acids which are the core substance of cells. These reactions can lead to alterations in the DNA protein of the cells as well as the polypeptide proteins and in turn this will cause cell injury.

Chemical Injury

The third form of cell injury is through chemicals that enter the human body and react with the plasma membrane of the cells thereby increasing their ability to permeate through the membrane. This increases the toxicity and it can also combine with organic chemicals to become free radicals. As a result, the cells are damaged.

Other reasons

Besides the above three reasons, the cells can also be injured due to pathological organisms that thrive in the human body and constantly look for ways and means to multiply. It is also caused by external injuries, inflammation, genetic factors, poor nutrition and extreme changes in external environment such as increased heat.

Cell Death

Irreversible cell injury is cell death and it can be broadly divided into Necrosis and Apoptosis. Necrosis is cell death that occurs due to an external stimuli like the presence of bacteria, fungi and other foreign substances whereas Apoptosis is the body's natural way of eliminating unwanted body cells. Necrosis is detrimental to the body and can even cause death, but Apoptosis is beneficial to the body because it removes the unwanted cells and boosts the growth of new cells in its place. Both these two kinds send different chemical signals to the immune system so that there is no accumulation of dead tissue near the area of cell death. Another difference is that in necrosis, the area of cell death is not a pleasant sight and in many cases, it has to be removed surgically. On the other hand, Apoptosis affects single cells that are widely scattered and so it is difficult for humans to even identify the cells that have been removed.

Necrosis can be broadly divided into seven types. The first type is the coagulative necrosis that occurs due to lack of oxygen and it primarily occurs in kidneys, heart and adrenal glands. The cell outline may be visible through a microscope and the tissues in the region are swollen. It is not caused by any other trauma or toxins and the cell death is only due to hypoxia. The blood vessels in the region fail to provide the required levels of oxygen and other nutrients to the cell and this results in the death of the cell. In this form of necrosis, the tissue architecture is not affected.

The second type is the liquefactive necrosis that mostly occurs in the brain and the brain cells that contain enzymes and liquids that results in the formation of pus and cysts. It can also be caused due to bacterial or fungal infections. In this kind of necrosis, the affected cell is consumed by the enzymes in the process of hydrolysis. After the cell is digested by these enzymes, in its area appears a lesion with pus. The white blood cells clean the affected area and it results in the formation of liquid fluids that leave a gap. This commonly occurs in the central nervous system and the lungs.

In Caseous Necrosis, the cells disintegrate and is typically caused by fungi such as tuberculosis. It is a combination of coagulative and liquefactive necrosis. Fatty necrosis occurs as a result of disintegration due to fatty enzymes called lipases and this is common in breasts and pancreas. Fibrinoid necrosis is caused by the presence of fiber-like protein substances in arterial walls. Hemorrhagic necrosis is due to blockage in the venal drainage of an organ and finally gangrenous necrosis occurs to hypoxia that is caused due to blockages in lower limbs.

Question 2: Please mention the differences between thrombosis and embolism

Answer:

Thrombosis is the blockage of a blood vessel by clots or thrombus. "A thrombus is formed from fibrin and blood elements called platelets deposited on the inner surface of the vessel. A thrombus may form in an artery damaged by arteriosclerosis, or in a vein when a person is immobilized for a long time" (Funk & Wagnalls New World Encyclopedia, 2009). The conditions that can lead to the development of thrombus are injury, infections, low blood pressure, inflammation and intimal irritation. The primary reason for the development of thrombus in veins is inflammation while in arteries, it is the anatomic changes that occur inside it. The development of thrombus may happen in a single area or it can spread to other parts too.

Embolism, on the other hand, is the obstruction caused by an embolus or a mass substance that can be a solid, liquid or gas. An embolus can be a gas bubble, a thrombus that has moved from its location, bacteria, cholesterol, fat, pus, tissue, hair or any other foreign substance. This embolus moves from one vessel to another and finally it gets stuck in a vessel that is too small for it to move through. In arterial embolism, the embolus attaches itself to the artery and blocks the flow of blood to other organs and in this case, the embolus is most likely to be a blood clot. In pulmonary embolism, this embolus occurs in the veins while an air embolus is likely to occur after a major injury when some large veins open. Cancer cells are also an embolus that can create havoc in the human body.

The primary difference between a thrombus and embolus is that the thrombus is stationary and it sits inside a vein while an embolus is in motion and constantly moves through veins until it gets to a vein that is too small. Also, a thrombus is a blood clot while an embolus can be any foreign substance. Another difference is that thrombosis usually occurs in the heart or any part of the circulatory system while embolism can occur in any part of the body.

Question 3: Describe the functions of the following cells in relation to inflammation. 1. Eosinophils 2. Basophils 3. Neutrophils 4. Monocyte 5. Lymphocyte 6. Erythrocytes (RBC)

Answer:

Eosinophils - Eosinophils are white blood cells and they are an integral part of the immunity system. They play a vital role in fighting infections, allergies and parasites. Acute inflammation causes numerous changes in these white blood cells. "The initial response to acute inflammation includes a rapid drop in numbers of circulating eosinophils, a rapid accumulation of eosinophils at the periphery of the inflammation site and an inhibition of egress of eosinophils from the bone marrow" (Bass, 1976, p.870).

Basophils- Basophils are one of the least common granulocytes and they make their appearance during certain inflammation, especially those that deal will allergies. They have two main functions during inflammation. The heparin substance found in basophils reduces blood clotting while vasodilator histamine in basophils increases blood flow to the tissues and organs.

Neutrophils -- Neutrophils are the most common white blood cells found in the human body and they are present in large numbers at the site of an inflammation. It produces destructive oxidizing agents that can convert dioxygen into hydrogen peroxide and in the process, they kill the bacteria or fungi that is causing the inflammation. They are a kind of phagocytes and have the ability to ingest any other cells. In the process of ingestion, they die and this makes their life a short-lived one. They have a life-span of four to ten hours when it is not in use and dies immediately after ingesting another cell. However, they are constantly produced and this makes the most abundant member of the human immune system. Besides ingesting bacteria, they also release a string of fibers called the neutrophil extracellular trap and this helps to trap the microbes or other particles present around the cell. This ensures that the entire region around the cell is cleaned by one neutrophil.

Monocyte -- Monocyte is a white blood cell that works to produce more macrophages and dendritic cells in human beings. During inflammation, they rush to the site and multiply into macrophages and dendritic cells that can fight the inflammation.

Lymphocyte -- Lymphocytes are a kind of white blood cells that play an active role in fighting inflammation along with the macrophages produced by monocytes. It produces limited amounts of secreted molecules such as interferon and they are also involved in cell to cell interactions. (Ross, 1994). There are three major kinds of lymphocytes and they are T cells, B cells and natural killer cells. The natural killer cells play a role in protecting the body from tumors by identifying these cells and releasing the cytotoxic granules that kill the affected cells. The Thymus (T cells) and Bone (B cells) identify the foreign particles and create a response that is specifically aimed to destroy these substances.

Erythrocytes -- Erythrocytes are the red blood cells in humans and they play a vital role in providing oxygen to the tissues. So, they provide the necessary oxygen at the site of inflammation to help the other cells to recover.

Question 4: Inflammation is the response of vascular tissues to harmful stimuli and also the protective attempt to remove them. Please describe the causes and course of inflammation.

Answer:

Inflammation is the biological process by which the body's white blood cells fight against infections and foreign substances such as bacteria and fungi. It is a protective response to external stimuli and when it occurs, the white blood cells rush to the site to fight the harmful stimuli. An inflammatory process begins when the tissue is damaged or malfunctioning due a variety of reasons other than injury, infection and foreign substances. This response is triggered by the body when it senses any malfunctioning or imbalance in homeostasis. Though these are of lower magnitude than an injury or infection, the body responds to it. In the case of tissue malfunctioning, the local WBCs present in the tissue fight the inflammation while larger problems such as injury require a more extensive response as mentioned below. (Medzhitov, 2008).