Pathophysiology and Cell injury

Pathophysiology and Cell injury

Pathophysiology versus pathology
While both terms indicate the study of disease, the term pathology is a broader term dealing with all aspects of a disease. This study is valuable for a physician or a pathologist who is also interested in the macro and microscopic characteristics of tissues and organs. On the other hand, in pathophysiology the focus is on the abnormal function of diseased organs, with application to diagnostic procedures leading patient care. Healthcare professionals are more concerned with pathophysiology when dealing with patients.

Disease and aetiology
The study of the cause of disease is called aetiology. Aetiology is the preferred spelling in some countries, including the UK, whereas ‘etiology’ without an ‘a’ is used in the USA. The word ‘aetiology’ comes from the Greek aitia, causea•›+a•›logos, discourse.

Diseases are described as genetic, congenital or acquired.
Genetic
In a disease where the cause is genetic, the person may have a defective gene that causes the disease. These defective genes are often passed on to children by parents. These abnormalities can range from a small mutation in a single gene to the addition or subtraction of an entire chromosome or set of chromosomes. Some genetic diseases are called Mendelian disorders (Figure 1.1); they are caused by mutations that occur in the DNA sequence of a single gene. These are usually rare diseases; some examples are Huntington’s disease and cystic fibrosis. Many genetic diseases are multifactorial – they are caused by mutations in several genes, compounded by environmental factors. Some examples of these are heart disease, cancer and diabetes.

Congenital
In congenital disease, the genetic information is intact; however, problems with the intrauterine environment may result in congenital disorder. For example, cystic fibrosis is a genetic disorder, whereas foetal alcohol syndrome results from the mother’s alcohol intake during pregnancy. This results in congenital abnormalities
in a child who is genetically normal (Figure 1.2).

Acquired
In this type of disease, the person develops the disease after birth as a result of direct or indirect contact with another person or the environment. Examples include tuberculosis, emphysema, chicken pox or acquired heart diseases.

Signs and symptoms
A symptom is generally subjective, while a sign is objective. Any objective evidence of a disease, such as blood in the stool or a skin rash, is a sign – it can be recognized by the doctor, nurse, family members and the patient. However, stomachache, lower?back pain, fatigue, for example, can only be detected or sensed by the patient – others only know about it if the patient tells them. For example, pain can either be acute or chronic. An example of acute pain is abdominal pain, which is sudden and may last only a few hours or longer. Common chronic pain complaints include headache, low back pain, cancer pain, arthritis pain, neurogenic pain (pain resulting from damage to the peripheral nerves or to the A?central nervous system itself), psychogenic pain (pain not due to past disease or injury or any visible sign of damage inside or A?outside the nervous system).

Pathogenesis
In assessing a patient’s signs and symptoms, conclusions can often be drawn about the pattern and development of a disease, in other words its pathogenesis. A typical pathogenesis involves kinds of tissue damage which produces certain effects. The progress of the disease can produce signs and symptoms throughout the course of the disease. Another aspect of pathogenesis is the time over which the A?disease develops. Some may be acute, while others are chronic. Acute conditions have a rapid onset with short duration, while chronic conditions last for a longer period which could be from months to years.

Investigations and diagnosis
In order to make a diagnosis, it may be necessary to carry out some investigations to confirm the diagnosis. Some of the investigations may be invasive, while others are not invasive. These may include blood test, CT scans, chest X?rays, endoscopy and many more. Diagnosis is identification of a condition, disease, disorder or problem by systematic analysis of the background or history, examination of the signs or symptoms, evaluation of the research or test results, and investigation of the assumed or probable causes. It is from the diagnosis that care or treatment is prescribed.

Treatment
Once a diagnosis is confirmed then the treatment can proceed.
The treatment is either medical or nursing treatment. The aim of
the treatment of a disease is to achieve a cure or minimize the
patient’s signs and symptoms to a degree where the patient can
function near normality.

Prognosis
Prognosis is a prediction of the chance of recovery or survival from a disease. Most doctors give a prognosis based on statistics of how a disease acts in studies on the general population. Prognosis can vary depending on several factors, such as the stage of disease at diagnosis, type of disease and even gender for A example cancer. Many factors can influence the prognosis of a patient with A cancer. Among the most important are the type and location of the cancer, the stage of the disease (the extent to which the cancer has spread in the body) and how quickly the cancer is likely to grow and spread. Other factors that affect prognosis include the biological and genetic properties of the cancer cells (biomarkers), the patient’s age and overall general health, and the extent to which the patient’s cancer responds to treatment.









Cell injury
The term ‘cell injury’ is used to indicate a state in which the capacity for physiological adaptation is exceeded by excessive stimuli, or when the cell is no longer capable to adapt without suffering some form of damage. Cell injury may be reversible or irreversible. Cell injury and cell death often result from exposure to toxic chemicals, infections and hypoxia.

Toxic chemicals
Chemical injury begins with the interaction between toxic chemicals and the plasma membrane. Many classes of toxic chemicals are capable of inducing acute cell injury followed by death. These include anoxia and ischaemia and their chemical analogues such as: potassium cyanide; chemical carcinogens, which form electrophiles that covalently bind to proteins in nucleic acids; oxidant chemicals, resulting in free radical formation and oxidant injury; activation of complement; and a variety of calcium ionophores. Cell death is also an important component of chemical carcinogenesis; many complete chemical carcinogens, at carcinogenic doses, produce acute necrosis and inflammation, followed by regeneration and preneoplasia.

Infections
Viruses induce cellular changes by two general mechanisms: (1) cytolytic and cytopathic viruses cause various degrees of A cellular injury and cell death, (2) oncogenic viruses stimulate host cell to proliferate and may induce tumours. Bacteria are relatively complex, single?celled creatures with a rigid wall and a thin, rubbery membrane surrounding the fluid inside the cell. They can reproduce on their own. Fossilized records show that bacteria have existed for about 3.5 billion years, and bacteria can survive in different environments, including extreme heat and cold, radioactive waste and the human body. Most bacteria are harmless, and some actually help by digesting food, destroying disease?causing microbes, fighting cancer cells and providing essential nutrients.

Hypoxia
Hypoxia is a deficiency of oxygen, which causes cell injury by reducing aerobic oxidative respiration. Hypoxia is an extremely important and common cause of cell injury and cell death. Causes of hypoxia include reduced blood flow, inadequate oxygenation of the blood due to cardiorespiratory failure and decreased oxygen?carrying capacity of the blood, as in anaemia or carbon monoxide poisoning (producing a stable carbon monoxyhaemoglobin that blocks oxygen carriage) or after severe blood loss. Depending on the severity of the hypoxic state, cells may adapt, undergo injury or die.

Adaptation
Cells adapt to the environment to escape and protect themselves from injury. Cellular adaptations are common and a central part of many disease states. The most significant adaptive states include atrophy, hypertrophy, hyperplasia and metaplasia.

Atrophy
Atrophy is a decrease or shrinkage in cell size caused by loss of subcellular organelles and substances (Figure 2.2). Atrophy can affect any, but it is most common in skeletal muscles, the heart, sex organs and the brain. However, physiological atrophy occurs in some glands. For example, the thymus gland undergoes physiological atrophy during childhood.

Hypertrophy
This is an increase in the size of the cells, thus enlarging the size of the organ (Figure 2.3). This can affect any cell but the cells of the heart, kidneys and skeletal muscles.

Hyperplasia
Hyperplasia is increased cell production in a normal tissue or organ. Hyperplasia may be a sign of abnormal or precancerous changes. This is called pathological hyperplasia. Hyperplasia may be harmless and occur on a particular tissue. An example of a normal hyperplastic response would be the growth and multiplication of milk?secreting glandular cells in the breast as a response to pregnancy, thus preparing for future breast?feeding.

Metaplasia
This is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus. An example of metaplasia is the replacement of normal columnar ciliated epithelial cells of the bronchial lining by striated squamous epithelial cells.
Cells that die due to necrosis do not follow the apoptotic signal transduction pathway, but rather various receptors are activated that result in the loss of cell membrane integrity and an uncontrolled release of products of cell death into the intracellular space. This initiates an inflammatory response in the surrounding tissue.
Nearby phagocytes are prevented from locating and engulfing the dead cells. The result is a build?up of dead tissue and cell debris at, or near, the site of the cell death.

Cell death
Cell death eventually leads to necrosis of the cell. It occurs when there is not enough blood flowing to the tissue, whether from injury, radiation, or chemicals. Necrosis is not reversible. One common type of necrosis is gangrene, which is often caused by damage from cold. There are many types of necrosis, as it can affect many areas of the body, including bone, skin, organs and other tissues.

Apoptosis
Apoptosis is derived from the Greek words apo, meaning away from, and ptosis, meaning to fall. The term ‘falling away from’ is derived from the fact that, during this type of prelethal change, the cells shrink and undergo marked blebbing at the periphery. The blebs then detach and float away. It is sometimes referred to as programmed cell death and, indeed, the process of apoptosis follows a controlled, predictable routine. However, it is normal for many cells to die of apoptosis as the nervous system forms; it is part of constructing appropriate connections. Apoptosis occurs in a variety of cell types following various types of toxic injury. It is especially prominent in lymphocytes, where it is the predominant mechanism for turnover of lymphocyte clones. The resulting fragments produce the basophilic bodies seen within macrophages in lymph nodes. In other organs, apoptosis typically occurs in single cells, which are rapidly cleared away before and following death by phagocytosis of the fragments by adjacent parenchymal cells or by macrophages. Apoptosis occurring
in single cells with subsequent phagocytosis typically does not result in inflammation. Prior to death, apoptotic cells show a very dense cytosol with normal or condensed mitochondria. The endoplasmic reticulum (ER) is normal or only slightly dilated.