Learn more about Pathophysiology
In this module, you will learn more about
- Useful terminology
- The response of cells to stressors: normal versus aberrant behaviour
- Inflammation
- Necrosis
- National Health Priority Areas (NHPAs)
Learn even more: See Chemistry and Cells
1 Useful terminology
Here are some frequently-used terms you should know. Starting with the most obvious :)
What does the term ‘pathophysiology’ mean?
Physiological processes within the body are the normal processes that lead to normal function.
These may alter with age and you will see diagnostic reports that state a measured deviation from normal is ‘physiological for age’.
For example, a computer tomography (CT) report notes, in a person of 95 years, that the ‘brain demonstrates atrophy physiological for age’. The report is clearly indicating the CT shows changes. But without any indication of declining cognition, this recognition of atrophy acknowledges that it may not be abnormal for this particular person.
Another example can be seen in athletes where their training can result in lowered heart rates, below the average person's because of increased aerobic capacity. Low HR and BP is physiologically normal for them, but not normal for an average person whose regular exercise routine does not include competition-level regimes.
In contrast, ‘pathophysiology’ is the study of abnormal or disordered processes that lead to disease. Homeostasis has been disrupted in some way. If the body is unable to compensate and return to normal function then damage will result.
These may alter with age and you will see diagnostic reports that state a measured deviation from normal is ‘physiological for age’.
For example, a computer tomography (CT) report notes, in a person of 95 years, that the ‘brain demonstrates atrophy physiological for age’. The report is clearly indicating the CT shows changes. But without any indication of declining cognition, this recognition of atrophy acknowledges that it may not be abnormal for this particular person.
Another example can be seen in athletes where their training can result in lowered heart rates, below the average person's because of increased aerobic capacity. Low HR and BP is physiologically normal for them, but not normal for an average person whose regular exercise routine does not include competition-level regimes.
In contrast, ‘pathophysiology’ is the study of abnormal or disordered processes that lead to disease. Homeostasis has been disrupted in some way. If the body is unable to compensate and return to normal function then damage will result.
Aetiology
This is the identified cause of disease or aberrant function. You will see this word spelt ‘etiology’ as well.
Epidemiology
The best description is that used by the World Health Organisation: “… the study of the distribution and determinants of health-related states or events (including disease), and the application of this study to the control of diseases and other health problems.”
Manifestations
This term refers to the patient’s presentation characteristics due to a pathological process.
For example, a bacterial infection will induce the manifestations of fever, chills, and fatigue and may or may not include nausea, vomiting or diarrhoea.
Knowing the pathogenesis of a disease can assist in predicting the manifestations of the disease and so helps the process of differential diagnosis.
For example, a bacterial infection will induce the manifestations of fever, chills, and fatigue and may or may not include nausea, vomiting or diarrhoea.
Knowing the pathogenesis of a disease can assist in predicting the manifestations of the disease and so helps the process of differential diagnosis.
Morbidity rate
The morbidity rate is relative to the incidence rate of a disease in a population. It is scaled to the size of a specific population.
Mortality rate
The mortality rate indicates the number of deaths within a population. It is scaled to the size of the specific population.
Pathogenesis
The description of the process, from the initial onset of disrupted physiology to the presentation of signs (objective measures such as blood pressure) and symptoms (subjective measures such as levels of pain), that are characteristic of a disease process.
Understanding the pathogenesis of a disease can help avoid the learning of great long lists of signs of symptoms for specific diseases because the process will help indicate what you would expect to see in a person with a particular problem.
Understanding the pathogenesis of a disease can help avoid the learning of great long lists of signs of symptoms for specific diseases because the process will help indicate what you would expect to see in a person with a particular problem.
Syndrome
A collection of signs and symptoms that are often found together without a clearly-associated pathogenesis.
For example, polycystic ovarian syndrome where ovarian cysts are only one sign of the disease process and the aetiology is not fully understood. Abnormal androgen levels are associated with the syndrome but the exact mechanisms of why and how have yet to be fully explained.
Another example is metabolic syndrome, a cluster of conditions that include increased blood pressure, increased waistline body fat, increased blood sugar and abnormal blood lipids. This syndrome is linked to the incidence of diabetes and cardiovascular diseases.
For example, polycystic ovarian syndrome where ovarian cysts are only one sign of the disease process and the aetiology is not fully understood. Abnormal androgen levels are associated with the syndrome but the exact mechanisms of why and how have yet to be fully explained.
Another example is metabolic syndrome, a cluster of conditions that include increased blood pressure, increased waistline body fat, increased blood sugar and abnormal blood lipids. This syndrome is linked to the incidence of diabetes and cardiovascular diseases.
2 The response of cells to stressors: normal versus aberrant behaviour
The cells and tissues of the body are dynamically functioning – something that is easy to forget when we are trying to simplify body processes in order to understand them.
We also need to broaden our understanding of the term ‘stress’ to include not only emotional stress but physical and chemical stress.
Stressors include anything that forces the body to adapt to its presence.
If undertaking physical exercise, then exercise is the stressor with the heart, lungs and skeletal muscles all endeavouring to compensate. The resultant changes are related to the increased workload and cell functions.
If we overindulge in alcoholic beverages then the stressor is the alcohol and the liver attempts to remove the toxin. Any excess it cannot remove damages liver cells which the body will attempt to replace.
We also need to broaden our understanding of the term ‘stress’ to include not only emotional stress but physical and chemical stress.
Stressors include anything that forces the body to adapt to its presence.
If undertaking physical exercise, then exercise is the stressor with the heart, lungs and skeletal muscles all endeavouring to compensate. The resultant changes are related to the increased workload and cell functions.
If we overindulge in alcoholic beverages then the stressor is the alcohol and the liver attempts to remove the toxin. Any excess it cannot remove damages liver cells which the body will attempt to replace.
Normal physiological responses
Normal adaptive cellular responses occur as controlled responses to stimuli. Once the stimulus is removed then the adaptive process ceases.
Hypertrophy
Hypertrophy is the term that describes the enlargement of a cell.
As cells within a group of cells enlarge, then so does the tissue it belongs to.
For example, skeletal muscle cells will enlarge in response to weight lifting as a result of the increased workload. The muscles consequently enlarge too. This is the normal response to the stressor - exercise.
As cells within a group of cells enlarge, then so does the tissue it belongs to.
For example, skeletal muscle cells will enlarge in response to weight lifting as a result of the increased workload. The muscles consequently enlarge too. This is the normal response to the stressor - exercise.
Atrophy
Atrophy is the term that describes cell shrinkage and consequently tissue shrinkage.
Skeletal muscles that are not used atrophy in response to lack of workload. Lack of nutrition leads to atrophy as cells decrease their size and energy usage. These examples are reversible.
Reproductive organ atrophy results from decreased endocrine stimulation and is most evident in women at menopause. This is a normal process related to aging.
Skeletal muscles that are not used atrophy in response to lack of workload. Lack of nutrition leads to atrophy as cells decrease their size and energy usage. These examples are reversible.
Reproductive organ atrophy results from decreased endocrine stimulation and is most evident in women at menopause. This is a normal process related to aging.
Hyperplasia
Hyperplasia is the term used to describe an increasing number of cells. This can be a normal response.
For example, hyperplasia occurs as a normal response to hormone changes related to oestrogen cycling and result in increased uterine endometrium cells as well as breast changes during pregnancy. Hypertrophy and hyperplasia often occur together, such as in pregnancy when eostrogen results in both uterine enlargement and cell number increases.
Another example is hepatic cell replacement to regenerate the liver following surgery, or the process of tissue healing as a result of trauma where cells must be replaced.
For example, hyperplasia occurs as a normal response to hormone changes related to oestrogen cycling and result in increased uterine endometrium cells as well as breast changes during pregnancy. Hypertrophy and hyperplasia often occur together, such as in pregnancy when eostrogen results in both uterine enlargement and cell number increases.
Another example is hepatic cell replacement to regenerate the liver following surgery, or the process of tissue healing as a result of trauma where cells must be replaced.
Intercellular accumulations
Cellular accumulations are the result of buildup of substances within cells that the cell cannot immediately use or eliminate.
An example of a normal cellular accumulation is melatonin in response to increased sun exposure. Lipids, carbohydrates and proteins are also stored for future use by the body.
Some cellular accumulations are deliberate such as in tattoos.
Cellular accumulations are the result of buildup of substances within cells that the cell cannot immediately use or eliminate.
An example of a normal cellular accumulation is melatonin in response to increased sun exposure. Lipids, carbohydrates and proteins are also stored for future use by the body.
Some cellular accumulations are deliberate such as in tattoos.
Aberrant responses
Abnormal responses are essentially maladaptive responses to a stressor where the body is unable to return to homeostasis. For example, chronic inflammation leads to constant release of growth factors resulting in increased cell division. Disease processes with related chronic inflammation have been associated with cancer.
Hypertrophy
Hypertrophy, as a pathological condition, can arise as compensatory process.
For example, valvular heart disease can cause obstruction to the blood flow through the chambers of the heart increasing the heart workload and resulting in thickening of the cardiac muscle as the cells enlarge.
Increased blood pressure can impact in the same way.
For example, valvular heart disease can cause obstruction to the blood flow through the chambers of the heart increasing the heart workload and resulting in thickening of the cardiac muscle as the cells enlarge.
Increased blood pressure can impact in the same way.
Atrophy
Atrophy of cells can occur as the result of a disease process such as Alzheimer’s disease that results in dementia. The brain atrophy that occurs is excessive and is not reversible. Ischaemia or lack of blood flow can also result in cell and tissue atrophy due to decreased capacity for cellular function.
Hyperplasia
Hyperplasia as a pathologic process is usually the result of abnormal hormonal stimulation or excess growth factor release.
Viruses can result in excess tissue by triggering growth factor production, for example, warts.
Hormone excess can be the result of an adenoma, for example a thyroid adenoma (a benign tumor), that results in an overproduction of thyroid hormone. This production is not under the control of the hypothalamus-pituitary-gland axis (HPA) feedback loop.
Viruses can result in excess tissue by triggering growth factor production, for example, warts.
Hormone excess can be the result of an adenoma, for example a thyroid adenoma (a benign tumor), that results in an overproduction of thyroid hormone. This production is not under the control of the hypothalamus-pituitary-gland axis (HPA) feedback loop.
Metaplasia
Metaplasia describes where an epithelial cell type is replaced by another epithelial cell type not normally found in a particular location.
An example is the replacement of ciliated epithelia cells with squamous (flat) epithelial cells. Ciliated epithelia cells line the bronchi and provide the mechanism for removal of mucous trapped microbes and foreign particles from the airways. These cells use the cilia (hair like structures) to transport the mucous to the mouth. Cigarette smoking is a known cause for metaplasia. The loss of the cilia reduces the capacity of the lungs to remove microbes and foreign particulates which increases the risk for lung infection.
An example is the replacement of ciliated epithelia cells with squamous (flat) epithelial cells. Ciliated epithelia cells line the bronchi and provide the mechanism for removal of mucous trapped microbes and foreign particles from the airways. These cells use the cilia (hair like structures) to transport the mucous to the mouth. Cigarette smoking is a known cause for metaplasia. The loss of the cilia reduces the capacity of the lungs to remove microbes and foreign particulates which increases the risk for lung infection.
Dysplasia
Dysplasia describes the loss of the normal shape and size of cells such that they no longer resemble the original cell structure. Dysplasia is reversible. It is considered the precursor to malignant (cancer) cell changes.
An example is the change seen in cervical cell smears that may or may not progress to cervical cancer (The PAP test). A test result that indicates dysplastic cell changes results in increased monitoring in order to detect the malignant cells at the earliest point in time for treatment.
An example is the change seen in cervical cell smears that may or may not progress to cervical cancer (The PAP test). A test result that indicates dysplastic cell changes results in increased monitoring in order to detect the malignant cells at the earliest point in time for treatment.
Intercellular accumulations
Notice the colour of the sclera of the eye in this patient with cholangitis jaundice.
Cellular accumulations can become pathological or be indicators of a pathological process occurring. Bilirubin accumulation leading to the sign of jaundice (yellowing of the skin) is an example of accumulation as an indicator of an aberrant process. It can occur when there is a decreased capacity for its removal as a result of liver disease, or when hepatic cells are overloaded due to increased red blood cell destruction. Other examples include excess lipid accumulation in the liver and abnormal protein accumulation in nerve cells.
Calcification is categorized as either dystrophic or metastatic. Dystrophic calcification occurs in injured tissue and is the result of deposition of calcium phosphate crystals which can be seen, for example, in atherosclerotic plaque, damaged heart valves and healed tuberculosis (TB) lesions. Metastatic calcification occurs as a result of increased plasma calcium levels with the calcium depositing into normal tissues. Hypercalcaemia (excess blood calcium) can result from excessive vitamin D intake, loss of calcium from bone due to bone metastasies or Paget’s disease (calcium reabsorption), renal failure and extended immobilization. Calcification of the heart valves can simply be the effect of aging due to deposition of plasma calcium on the valves over time.
Cellular accumulations can become pathological or be indicators of a pathological process occurring. Bilirubin accumulation leading to the sign of jaundice (yellowing of the skin) is an example of accumulation as an indicator of an aberrant process. It can occur when there is a decreased capacity for its removal as a result of liver disease, or when hepatic cells are overloaded due to increased red blood cell destruction. Other examples include excess lipid accumulation in the liver and abnormal protein accumulation in nerve cells.
Calcification is categorized as either dystrophic or metastatic. Dystrophic calcification occurs in injured tissue and is the result of deposition of calcium phosphate crystals which can be seen, for example, in atherosclerotic plaque, damaged heart valves and healed tuberculosis (TB) lesions. Metastatic calcification occurs as a result of increased plasma calcium levels with the calcium depositing into normal tissues. Hypercalcaemia (excess blood calcium) can result from excessive vitamin D intake, loss of calcium from bone due to bone metastasies or Paget’s disease (calcium reabsorption), renal failure and extended immobilization. Calcification of the heart valves can simply be the effect of aging due to deposition of plasma calcium on the valves over time.
3 Inflammation
Inflammation is the process of the body responding to cellular and tissue injury. It can be categorised as acute or chronic.
The cardinal signs of inflammation are: redness, swelling, heat, pain and loss of function.
Cells, when damaged, release arachidonic acid. Cyclo-oxygenase converts this to prostaglandin. Prostaglandins have three actions:
This response accounts for the signs of oedema (tissue swelling), pain and the systemic effect of raised temperature (heat).
Increased blood flow to the site also adds to the localised rise in tissue temperature (heat) and the redness of the damaged area.
Cell membrane damage also triggers mast cells (stationary immune response cells similar to basophils) to release histamine. Histamine increases blood flow to the site and vessel permeability contributing to the oedema, redness and heat.
Tissue damage also causes the release of platelet activating factor enabling the clotting sequence to seal the wound site (‘haemostasis’ means to ‘stop flow of blood’).
Cells, when damaged, release arachidonic acid. Cyclo-oxygenase converts this to prostaglandin. Prostaglandins have three actions:
- induce the hypothalamus to increase the body temperature set-point
- sensitise the nociceptors (pain receptors) to increase messages to the nervous system indicating damage and to generate pain, and
- increase the vessel permeability allowing white blood cells and fluid into the damaged site
This response accounts for the signs of oedema (tissue swelling), pain and the systemic effect of raised temperature (heat).
Increased blood flow to the site also adds to the localised rise in tissue temperature (heat) and the redness of the damaged area.
Cell membrane damage also triggers mast cells (stationary immune response cells similar to basophils) to release histamine. Histamine increases blood flow to the site and vessel permeability contributing to the oedema, redness and heat.
Tissue damage also causes the release of platelet activating factor enabling the clotting sequence to seal the wound site (‘haemostasis’ means to ‘stop flow of blood’).
The timeline for inflammation and healing
The inflammatory response results in the release of chemicals that act as growth factors stimulating cells to divide in order that damaged cells are replaced.
In acute inflammation the process resolves in either healing of the damaged site without scar tissue, or in fibrosis and scarring.
However, in chronic inflammation the acute process becomes self-perpetuating and can last from months to years. This can lead to excessive fibrosis and scar tissue formation.
In acute inflammation the process resolves in either healing of the damaged site without scar tissue, or in fibrosis and scarring.
However, in chronic inflammation the acute process becomes self-perpetuating and can last from months to years. This can lead to excessive fibrosis and scar tissue formation.
4 Necrosis
Necrosis is cell death as the result of trauma, ischaemia or hypoxia.
Apoptosis is the term used to describe programmed cell death. It does not generate an inflammatory response. It occurs to remove old cells allowing space for the replacements. It occurs as part of healing and is possibly most apparent in the development of the embryo.
In contrast, necrosis is cell death as the result of trauma, ischaemia or hypoxia. Necrosis is irreversible. The dead cells release their components and enzymes which then effect nearby cells inducing an inflammatory response. Necrosis can be categorised as:
In contrast, necrosis is cell death as the result of trauma, ischaemia or hypoxia. Necrosis is irreversible. The dead cells release their components and enzymes which then effect nearby cells inducing an inflammatory response. Necrosis can be categorised as:
- Coagulative necrosis, which results from acid denaturing of proteins in response to severe ischaemia and infarction;
- Liquifactive necrosis, which results from cell death release of cellular enzymes;
- Caseous necrosis, which is the result of both liquifactive and coagulative processes where the dead cells persist indefinitely. It is seen in tuberculosis granulomas;
- Fat necrosis, which is the result of lipase releasing fatty acids from adipose tissue that then combine with minerals to form a type of soap; and,
- Gangrene necrosis, which occurs as the result of arterial blood flow obstruction leading to large areas of tissue hypoxia. In dry gangrene the tissues dry out and shrink, whereas in wet gangrene white blood cell invasion leads to liquifactive necrosis. Gas gangrene results from infection with Clostridium spp. usually following trauma. The bacteria release toxins that digest the cell membranes of infected tissue.
5 National Health Priority Areas (NHPAs)
The National Health Priority Areas are identified areas that significantly contribute to Australia’s disease burden and health costs.
They are economically important as they may diminish the capacity to work and engage with community making them also important on a social level.
The potential negative impact on an individual’s capacity to live a life well is not only critical to one’s mental health, but also to community wellness.
The NHPAs agreed by the Australian Health Ministers’ Advisory Council are:
They are economically important as they may diminish the capacity to work and engage with community making them also important on a social level.
The potential negative impact on an individual’s capacity to live a life well is not only critical to one’s mental health, but also to community wellness.
The NHPAs agreed by the Australian Health Ministers’ Advisory Council are:
- Cancer control
- Cardiovascular health
- Injury prevention and control
- Mental health
- Diabetes mellitus
- Asthma
- Arthritis and musculoskeletal conditions
- Obesity
- Dementia