{"id":5,"date":"2023-05-23T17:08:05","date_gmt":"2023-05-23T21:08:05","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?p=5"},"modified":"2026-06-04T21:57:52","modified_gmt":"2026-06-05T01:57:52","slug":"introduction-to-pathophysiology","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/introduction-to-pathophysiology\/","title":{"raw":"Section 1: Key Terminology","rendered":"Section 1: Key Terminology"},"content":{"raw":"\"Staff<\/a>\r\n\r\n \r\n\r\nThis chapter introduces the foundational<\/span>\u00a0<\/span>vocabulary<\/strong>\u00a0used in<\/span>\u00a0pathophysiology,<\/span>\u00a0along with an overview of <\/span>cellular responses<\/span><\/strong> to <\/span>stress, <\/span><\/strong>injury, and aging<\/strong>.<\/span>\r\n
<\/div>\r\n

The 'P' Words:\u00a0 Pathology, Pathophysiology, Pathogen, and Pathogenesis.<\/strong><\/span><\/h3>\r\nPathology<\/strong>\u00a0is<\/span> the study of a cell or tissue changes due to disease.\u00a0 The word breaks down neatly;\u00a0 pathos<\/strong> (Greek for disease or pain) + -ology<\/strong> (the study of).\r\n\r\nBuilding on this, physiology<\/strong> is the study of the function of a particular structure within the human body, and anatomy is the study of a particular structure.\u00a0 Combining these concepts, pathophysiology<\/strong> refers to the study of abnormalities in the function of a particular structure of the human body as a result of disease.<\/span>\r\n\r\nA <\/span>pathogen<\/span><\/strong>\u00a0is <\/span>any microorganism that<\/span>\u00a0causes disease - this could be a bacterium,<\/span> virus, fungi (e.g., yeast),<\/span> helminth (parasitic worm), or protozoa.<\/span>\r\n\r\nPathogenesis.<\/strong><\/span> refers to the mechanism of disease and all the steps that unfold as a disease progresses.\u00a0 Breaking down the word:\u00a0 pathos-<\/strong> ('suffering') +<\/span>\u00a0genesis<\/strong> ('creation of').\u00a0 Pathogenesis includes all events occurring<\/span> at the cellular, molecular, organ, and organ system level.\u00a0 \u00a0<\/span>\r\n\r\nFinally, a lesion<\/strong> is defined<\/span>\u00a0as the anatomic abnormality of a disease - i<\/span>t might be an open wound,<\/span>\u00a0tissue damaged by a pathogen, a broken bone, or<\/span>\u00a0a cancerous growth.<\/span>\r\n\r\n[caption id=\"attachment_2299\" align=\"alignnone\" width=\"200\"]\"\"<\/a> Ancient Romans often dedicated votive objects to specific gods associated with healing in the hopes of recovery. These objects were in the form or representation of the affected body part and would be left at the temple of a god.
This torso was created in the image of a man's torso, dissected so that the internal organs could be seen, and was probably dedicated to heal someone suffering from internal disease or injury. Made c. 200 BCE - 200 CE, most likely in Isola Farnese, Italy. The piece is now part of the collection of the Science Museum in London, UK.[\/caption]\r\n\r\n
<\/div>\r\n\r\n[caption id=\"attachment_160\" align=\"alignnone\" width=\"260\"]\"\"<\/a> A fresco depicting the Greco-Roman mythology of Iapyx (the healer) removing an arrowhead from the Trojan hero Aeneas' thigh. Venus stands over while beside Aeneas stands his young son Ascanius. 1st century CE (between 45 and 79 CE), from Pompeii. (Naples National Archaeological Museum)<\/em>.[\/caption]\r\n

What is Disease?\u00a0 What is Considered Healthy?<\/strong><\/span><\/h3>\r\n

To understand disease<\/strong>, we must first understand what is considered healthy.<\/strong>\u00a0 Disease is most often accompanied by indicators that signal that something is negatively affecting normal physiology, either temporarily or permanently.<\/span><\/p>\r\n

Normal physiology is understood through the concept of a normal range<\/strong> - a set of physiological measurements conducive to organ and tissue homeostasis<\/strong> and physical wellbeing.\u00a0 Homeostasis (from Greek<\/span> 'homoiosis' meaning 'same' and stasis<\/strong> meaning 'standing'') refers to the relatively stable internal environment that allows for optimal functioning of all of the tissues, organs, and organ systems.<\/p>\r\n

Examples of body measurements with normal ranges include:\u00a0 blood pressure, heart rate, body temperature, water and electrolyte levels, oxygen, carbon dioxide and pH levels, nutritional compounds (e.g., amino acids), waste compounds (e.g., urea), and hormones.\u00a0 It is important to note that these ranges differ by individual factors.<\/p>\r\n\r\n

\r\n

Example:\u00a0 Heart Rate and Its Many Influences<\/strong><\/p>\r\n\r\n<\/header>\r\n

\r\n\r\nHeart rate is a good example of how normal ranges depend on context.\u00a0 Heart rate typically varies depending on: body size, biological sex, age, body composition, fitness level, exertion level<\/strong> (rest vs. exercise), and lifestyle<\/strong> (e.g., smokers tend to have higher resting heart rates).\r\n\r\nFor instance, in comparison to age-matched males, females<\/strong> tend to have higher heart rates during rest and exercise.\u00a0 This is thought to be due to females having smaller<\/strong> heart sizes in proportion to stature as well as differences in body composition.\r\n\r\nLikewise, infants<\/strong> have smaller hearts and higher heart rates than children, who have smaller hearts and higher heart rates than adults.\r\n\r\nSimilarly, trained athletes<\/strong> typically have lower resting heart rates<\/strong> than sedentary individuals, often due to the impact of training on heart size and strength.\r\n\r\n<\/div>\r\n<\/div>\r\n\r\n[caption id=\"attachment_2209\" align=\"alignnone\" width=\"300\"]\"Example<\/a> Example of nutritional deficiency: Hyperpigmentation of knuckles, along with other parts of the extremities, is characteristic of vitamin B12 deficiency.[\/caption]\r\n

How does Disease affect Homeostasis?<\/strong><\/span><\/h3>\r\n

When disease<\/span> negatively affects the functioning of cells, tissues, organs, or organ systems, homeostasis<\/strong> can be disrupted.\u00a0 If cells, tissues, and\/or organs cannot maintain homeostasis\u00a0<\/span>over time, more cells throughout the body become affected, slow in function, and may eventually die. <\/span><\/p>\r\n

It is worth clarifying that not all difference from the \"average\" represent disease.\u00a0 For example, a person born blind or with a hearing impairment is not usually experiencing a disease - these differences do not negatively impact organ function or cellular homeostasis.\u00a0 When we speak of disease<\/strong>, disorder<\/strong> or pathophysiology,<\/strong> we are referring to conditions that<\/span>\u00a0affect cellular homeostasis<\/strong><\/span>\u00a0in a negative way.<\/span><\/p>\r\n\r\n

Circadian Rhythm and the Expected Fluctuations in Physiological Measurements<\/span><\/strong><\/h3>\r\n

Health care professionals must account for normal expected daily fluctuations<\/strong> in physiological measurements. When you sleep, your body temperature drops by approximately 1\u00baC.\u00a0 Two key hormones govern the daily cycle:<\/span><\/p>\r\n \r\n\r\n \r\n\r\n\r\n\r\n\r\n
Cortisol<\/strong> (the waking hormone)<\/span><\/td>\r\nProduced by the adrenal cortex.\u00a0 Plasma levels rise in the morning thought to induce wakefulness and alertness.<\/td>\r\n<\/tr>\r\n
Melatonin<\/strong> (the sleeping hormone)<\/span><\/td>\r\nSecreted by the pineal gland.\u00a0 Plasma levels rise in the evening response to darkness, inducing sleepiness and maintaining the daily circadian rhythm.<\/strong><\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n \r\n\r\n[caption id=\"attachment_181\" align=\"alignnone\" width=\"300\"]\"\"<\/a> The normal synchronous relationships between sleep and daytime-activity and cortisol.
Hickie, I, Naismith, S., Robillard, R, Scott, E, Hermens, D. (2013). BMC medicine. 11. 79. 10.1186\/1741-7015-11-79<\/em>.[\/caption]\r\n

Disease, Disorder, and Syndrome - What is the Difference?<\/strong><\/span><\/h3>\r\nThese three terms are sometimes used interchangeably, but they have distinct meanings:<\/span>\r\n\r\n\r\n\r\n\r\n\r\n
Disease<\/strong><\/span><\/td>\r\nA physiological or biological ailment either an underlying cause that may result in anatomical changes that are temporary or permanent.\u00a0<\/span><\/td>\r\n<\/tr>\r\n
Disorder<\/strong><\/span><\/td>\r\nAs defined by the National Institutes of Health (NIH):\u00a0 a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.<\/td>\r\n<\/tr>\r\n
Syndrome<\/strong><\/span><\/td>\r\nA cluster of various signs and symptoms that can vary over time and together suggest the presence of - or increased risk for - a particular disease.<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n \r\n\r\n[caption id=\"attachment_188\" align=\"alignnone\" width=\"291\"]\"\"<\/a> Woodcutting of a plague-stricken man lying in bed, attended by three physicians. From the Pestbuch, a 16th Century CE medical treatise by Hieronymous Brunschwig (c. 1450-1512 CE). (Courtesy of the Historical Medical Library of The College of Physicians of Philadelphia)[\/caption]\r\n

Terms to Describe Duration,<\/span> Severity, and Stages of Disease<\/strong><\/span><\/h3>\r\nSeveral important terms convey how quickly a disease develops, how severe it is, and how it progresses over time:<\/span>\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n
Acute Onset<\/strong><\/span><\/td>\r\nSudden onset with severe symptoms.<\/td>\r\n<\/tr>\r\n
Insidious Onset<\/strong><\/span><\/td>\r\nGradual onset with mild symptoms that become more pronounced over time.<\/td>\r\n<\/tr>\r\n
Acute Illness<\/strong><\/span><\/td>\r\nA sudden, severe, and typically short-term illness.<\/td>\r\n<\/tr>\r\n
Chronic Illness<\/strong><\/span><\/td>\r\nAn illness lasting longer than 3 months, often starting with mild symptoms.<\/td>\r\n<\/tr>\r\n
Remission<\/strong><\/span><\/td>\r\nA period within a chronic illness when the person recovers somewhat and feels better.<\/td>\r\n<\/tr>\r\n
Relapse<\/strong><\/span><\/td>\r\nA period within a chronic illness when the disease worsens.<\/td>\r\n<\/tr>\r\n
Subacute<\/strong><\/span><\/td>\r\nNot as severe as acute illness and shorter than a chronic illness (sub- = below\/less)<\/td>\r\n<\/tr>\r\n
Subclinical<\/strong><\/span><\/td>\r\nEarly stage of disease in which no signs or symptoms are present; detectable only by sensitive and specific tests (e.g., imagining, or lab tests)<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n
\r\n

\r\nA Note on Chronic Pain<\/strong><\/p>\r\n\r\n<\/header>\r\n

\r\n\r\nCurrent literature suggests that chronic pain<\/strong> is not always proportional to biological or physiological damage.\u00a0 In some cases, damage exists without pain; in others, pain persists after the damage has been resolved.\u00a0 Many internal and external factors contribute to chronic pain and treatment is therefore highly individualized, potentially involving physical rehabilitation, lifestyle strategies, and therapeutic counselling.\r\n\r\n<\/div>\r\n<\/div>\r\n

Latent Stage, Incubation Stage and Prodromal<\/span> Period<\/span><\/strong>\u00a0<\/span><\/strong><\/span><\/h3>\r\n

These terms are closely related and are often confused.\u00a0 The key is to distinguish between infections and non-infectious scenarios, and to understand what each stage begins and ends with.<\/span><\/p>\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n
Subclinical<\/strong><\/span><\/td>\r\nNo signs or symptoms; disease is present but undetectable by routine exam<\/td>\r\n<\/tr>\r\n
Incubation Stage<\/strong><\/span><\/td>\r\nApplies only to infectious disease<\/strong>.\u00a0 Begins when the pathogen enters the body; end with signs and symptoms<\/strong> develop.<\/td>\r\n<\/tr>\r\n
Latent Stage of Infectious Disease<\/strong><\/span><\/td>\r\nBegins when a pathogen enters the body; ends when the person becomes infectious (contagious)<\/strong>.\u00a0 Most often overlaps with the incubation stage.<\/td>\r\n<\/tr>\r\n
Latent Stage of Non-Infectious Disease<\/strong><\/span><\/td>\r\nBegins with the start of the disease (e.g., the first cancerous cell); ends when the disease becomes detectable by testing<\/strong>.<\/td>\r\n<\/tr>\r\n
Prodromal<\/strong><\/span><\/td>\r\nThe first time<\/strong> that signs or symptoms of illness are noticed (e.g., a scratchy throat at teh onset of a cold or flu).<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n \r\n\r\n[caption id=\"attachment_5727\" align=\"alignnone\" width=\"300\"]\"Graph<\/a> Four Stages of Infection: All infections (localize and systemic) go through four stages. The first stage known as the Incubation Period begins when a pathogen enters the body and ends when a person begins to show signs and symptoms. The incubation period typically lasts 1-3 days and is characterized by pathogen amplification (by multiplying) and spread to affect many cells. The incubation period often overlaps with the Latent Period, which also begins once the pathogen has successfully adhered to host cells. Latency is said to end when the person becomes infectious and is capable of spreading the pathogen to other hosts. The next stage is the Prodromal Stage which is characterized by the initial appearance of mild or vague symptoms. The third stage is termed Illness and is when a person experiences signs and symptoms related to the damage being caused by the pathogen along with the effects of the immune system's response. The period of Convalescence is characterized by healing and recovery and coincide with the diminishment of pathogen particle numbers in the body as well as the fading out of signs and symptoms.[\/caption]\r\n\r\n
\r\n

Real-World Application:\u00a0 COVID-19 and Silent Spreaders<\/strong><\/p>\r\n\r\n<\/header>\r\n

\r\n\r\nStudies of SARS-CoV-2 (COVID-19) viral infections revealed an important distinction.\u00a0 While the incubation stage<\/strong> often directly overlaps with the latent stage<\/strong> of an infection, it was found that with COVID-19, the infectious stage can occur before<\/strong> signs and symptoms develop.\u00a0 This means the latent stage can end<\/strong> and the infectious stage can begin while a person still appears healthy - a phenomenon known as 'silent spreading'.<\/strong>\u00a0 This differs from most respiratory infections such as colds and flu, where the infectious stage coincides with the appearance of symptoms like a runny nose and coughing.\r\n\r\n<\/div>\r\n<\/div>\r\n\r\n[caption id=\"attachment_2200\" align=\"alignnone\" width=\"300\"]\"Example<\/a> Mary Mallon, nicknamed \"Typhoid Mary\", worked as a household cook for several New York families between 1897 and 1907. She was an asymptomatic \"silent\" carrier of Salmonella typhi, the pathogenic bacterium that causes typhoid fever. Due to her subclinical infection (an infection that caused few\/no signs), she infamously infected up to fifty-seven people, leading to three confirmed deaths. In the middle of this time period, she was forced into quarantine at Riverside Hospital and upon release was not permitted to return to cooking as a career - a promise which she did not adhere to resulting in twenty-five of the cases and two of the deaths. Her case continues to raise ethical questions about the protection of individual liberty, the safe-guarding of public health, and the treatment of infected individuals in both the courts and in public media. Salmonella typhi can cause a persistent subclinical infection of the gallbladder and exhibits fecal-oral transmission. This case also illustrates the importance of access to modern indoor plumbing, clean water and sanitation. (New York American (1909)).[\/caption]\r\n

The Four Stages of Infection<\/strong><\/span><\/h3>\r\nAll infections - localized and systemic - progress through four stages:\r\n\r\n\r\n\r\n\r\n\r\n\r\n
Incubation Period<\/strong><\/span><\/td>\r\nBegins when a pathogen enters the body; ends when signs and symptoms appear.\u00a0 Typically lasts 1-3 days; characterized by pathogen amplification and spread.\u00a0 Often overlaps with the Latent Period.<\/td>\r\n<\/tr>\r\n
Prodromal Stage<\/strong><\/span><\/td>\r\nCharacterized by the initial appearance of mild or vague symptoms.<\/td>\r\n<\/tr>\r\n
Illness<\/strong><\/span><\/td>\r\nThe person experiences signs and symptoms related to damage caused by the pathogen and the immune system's response.<\/td>\r\n<\/tr>\r\n
Convalescence<\/strong><\/span><\/td>\r\nRecovery and healing, coinciding with diminishing pathogen numbers and the fading of signs and symptoms.<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n

Local vs. Systemic:\u00a0 Where Does is Affect the Body?<\/strong><\/span><\/h3>\r\n\r\n\r\n\r\n\r\n
Local<\/strong><\/span><\/td>\r\nOnly a specific, discrete area of the body<\/strong> is affected (e.g., a localized wound or infection).<\/td>\r\n<\/tr>\r\n
Systemic<\/strong><\/span><\/td>\r\nThe illness affects the whole body<\/strong> (e.g., a fever or hypertension, which affects blood pressure throughout the entire body).\u00a0 A fever that heats up the whole body is another example.<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n

Complication, Sequelae, and Convalescence<\/strong><\/span><\/h3>\r\nAs a disease progresses, additional complications may arise.\u00a0 It is important to distinguish between a complication and a sequela:\r\n\r\n\r\n\r\n\r\n\r\n
Complication<\/strong><\/span><\/td>\r\nThe development of further negative conditions<\/strong> arising from the original illness (e.g., a heart attack results in the formation of a blood clot that travels to an organ depriving it of blood flow).<\/td>\r\n<\/tr>\r\n
Sequelae<\/strong><\/span><\/td>\r\nPermanent or long-term impairment<\/strong> resulting from a disease or complication - from the Latin word sequi,<\/strong> meaning 'follow' (e.g., kidney failure following poorly managed diabetes; or paralysis following a stroke).<\/td>\r\n<\/tr>\r\n
Convalescence<\/strong><\/span><\/td>\r\nThe period of recovery<\/strong>, which may involve rehabilitation exercises, speech therapy, improved mobility strategies, or other lifestyle changes.<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n
\r\n

Examples of Sequelae<\/strong><\/p>\r\n\r\n<\/header>\r\n

\r\n\r\nChronic Example - Diabetes:<\/strong>\u00a0 If diabetes is poorly managed over time, permanent biological damage can accumulate in blood vessels throughout the body.\u00a0 Common complications of vascular damage include chronic kidney disease, which may lead to kidney failure, requiring dialysis and placement on a transplant waiting list.\u00a0 Kidney failure<\/strong> in this context is a sequela<\/strong> of diabetes.\r\n\r\nAcute Example - Stroke (CVA, cerebrovascular accident):\u00a0<\/strong> A stroke affecting the left cerebral hemisphere in the frontal lobe may result in paralysis on the right side of the body.\u00a0 Some recovery is possible depending on stroke severity and treatment, but some paralysis<\/strong> is often permanent - this is a sequela.<\/strong>\r\n\r\nMental Health Example - PTSD:\u00a0<\/strong> Post-Traumatic Stress Disorder (PTSD) can develop following trauma (e.g., soldiers returning from war).\u00a0 If it becomes a long-term or permanent mental health impairment, it is considered a sequela of the trauma.\u00a0 Encouragingly, individualized and emerging treatments offer pathways to recovery.\r\n\r\n<\/div>\r\n<\/div>\r\n \r\n\r\n[caption id=\"attachment_2202\" align=\"alignnone\" width=\"300\"]\"Example<\/a> Convalescence is the period following illness, injury, or surgery during which the body recovers and may require changes in lifestyle. During convalescence following a total knee replacement, patients are encouraged to walk to aid in the healing process.[\/caption]\r\n\r\n \r\n

[h5p id=\"12\"]<\/p>\r\n[h5p id=\"16\"]","rendered":"

\"Staff<\/a><\/p>\n

 <\/p>\n

This chapter introduces the foundational<\/span>\u00a0<\/span>vocabulary<\/strong>\u00a0used in<\/span>\u00a0pathophysiology,<\/span>\u00a0along with an overview of <\/span>cellular responses<\/span><\/strong> to <\/span>stress, <\/span><\/strong>injury, and aging<\/strong>.<\/span><\/p>\n

<\/div>\n

The ‘P’ Words:\u00a0 Pathology, Pathophysiology, Pathogen, and Pathogenesis.<\/strong><\/span><\/h3>\n

Pathology<\/strong>\u00a0is<\/span> the study of a cell or tissue changes due to disease.\u00a0 The word breaks down neatly;\u00a0 pathos<\/strong> (Greek for disease or pain) + -ology<\/strong> (the study of).<\/p>\n

Building on this, physiology<\/strong> is the study of the function of a particular structure within the human body, and anatomy is the study of a particular structure.\u00a0 Combining these concepts, pathophysiology<\/strong> refers to the study of abnormalities in the function of a particular structure of the human body as a result of disease.<\/span><\/p>\n

A <\/span>pathogen<\/span><\/strong>\u00a0is <\/span>any microorganism that<\/span>\u00a0causes disease – this could be a bacterium,<\/span> virus, fungi (e.g., yeast),<\/span> helminth (parasitic worm), or protozoa.<\/span><\/p>\n

Pathogenesis.<\/strong><\/span> refers to the mechanism of disease and all the steps that unfold as a disease progresses.\u00a0 Breaking down the word:\u00a0 pathos-<\/strong> (‘suffering’) +<\/span>\u00a0genesis<\/strong> (‘creation of’).\u00a0 Pathogenesis includes all events occurring<\/span> at the cellular, molecular, organ, and organ system level.\u00a0 \u00a0<\/span><\/p>\n

Finally, a lesion<\/strong> is defined<\/span>\u00a0as the anatomic abnormality of a disease – i<\/span>t might be an open wound,<\/span>\u00a0tissue damaged by a pathogen, a broken bone, or<\/span>\u00a0a cancerous growth.<\/span><\/p>\n

\"\"<\/a>
Ancient Romans often dedicated votive objects to specific gods associated with healing in the hopes of recovery. These objects were in the form or representation of the affected body part and would be left at the temple of a god.
This torso was created in the image of a man’s torso, dissected so that the internal organs could be seen, and was probably dedicated to heal someone suffering from internal disease or injury. Made c. 200 BCE – 200 CE, most likely in Isola Farnese, Italy. The piece is now part of the collection of the Science Museum in London, UK.<\/figcaption><\/figure>\n
<\/div>\n
\"\"<\/a>
A fresco depicting the Greco-Roman mythology of Iapyx (the healer) removing an arrowhead from the Trojan hero Aeneas’ thigh. Venus stands over while beside Aeneas stands his young son Ascanius. 1st century CE (between 45 and 79 CE), from Pompeii. (Naples National Archaeological Museum)<\/em>.<\/figcaption><\/figure>\n

What is Disease?\u00a0 What is Considered Healthy?<\/strong><\/span><\/h3>\n

To understand disease<\/strong>, we must first understand what is considered healthy.<\/strong>\u00a0 Disease is most often accompanied by indicators that signal that something is negatively affecting normal physiology, either temporarily or permanently.<\/span><\/p>\n

Normal physiology is understood through the concept of a normal range<\/strong> – a set of physiological measurements conducive to organ and tissue homeostasis<\/strong> and physical wellbeing.\u00a0 Homeostasis (from Greek<\/span> ‘homoiosis’ meaning ‘same’ and stasis<\/strong> meaning ‘standing”) refers to the relatively stable internal environment that allows for optimal functioning of all of the tissues, organs, and organ systems.<\/p>\n

Examples of body measurements with normal ranges include:\u00a0 blood pressure, heart rate, body temperature, water and electrolyte levels, oxygen, carbon dioxide and pH levels, nutritional compounds (e.g., amino acids), waste compounds (e.g., urea), and hormones.\u00a0 It is important to note that these ranges differ by individual factors.<\/p>\n

\n
\n

Example:\u00a0 Heart Rate and Its Many Influences<\/strong><\/p>\n<\/header>\n

\n

Heart rate is a good example of how normal ranges depend on context.\u00a0 Heart rate typically varies depending on: body size, biological sex, age, body composition, fitness level, exertion level<\/strong> (rest vs. exercise), and lifestyle<\/strong> (e.g., smokers tend to have higher resting heart rates).<\/p>\n

For instance, in comparison to age-matched males, females<\/strong> tend to have higher heart rates during rest and exercise.\u00a0 This is thought to be due to females having smaller<\/strong> heart sizes in proportion to stature as well as differences in body composition.<\/p>\n

Likewise, infants<\/strong> have smaller hearts and higher heart rates than children, who have smaller hearts and higher heart rates than adults.<\/p>\n

Similarly, trained athletes<\/strong> typically have lower resting heart rates<\/strong> than sedentary individuals, often due to the impact of training on heart size and strength.<\/p>\n<\/div>\n<\/div>\n

\"Example<\/a>
Example of nutritional deficiency: Hyperpigmentation of knuckles, along with other parts of the extremities, is characteristic of vitamin B12 deficiency.<\/figcaption><\/figure>\n

How does Disease affect Homeostasis?<\/strong><\/span><\/h3>\n

When disease<\/span> negatively affects the functioning of cells, tissues, organs, or organ systems, homeostasis<\/strong> can be disrupted.\u00a0 If cells, tissues, and\/or organs cannot maintain homeostasis\u00a0<\/span>over time, more cells throughout the body become affected, slow in function, and may eventually die. <\/span><\/p>\n

It is worth clarifying that not all difference from the “average” represent disease.\u00a0 For example, a person born blind or with a hearing impairment is not usually experiencing a disease – these differences do not negatively impact organ function or cellular homeostasis.\u00a0 When we speak of disease<\/strong>, disorder<\/strong> or pathophysiology,<\/strong> we are referring to conditions that<\/span>\u00a0affect cellular homeostasis<\/strong><\/span>\u00a0in a negative way.<\/span><\/p>\n

Circadian Rhythm and the Expected Fluctuations in Physiological Measurements<\/span><\/strong><\/h3>\n

Health care professionals must account for normal expected daily fluctuations<\/strong> in physiological measurements. When you sleep, your body temperature drops by approximately 1\u00baC.\u00a0 Two key hormones govern the daily cycle:<\/span><\/p>\n

 <\/p>\n

 <\/p>\n\n\n\n\n
Cortisol<\/strong> (the waking hormone)<\/span><\/td>\nProduced by the adrenal cortex.\u00a0 Plasma levels rise in the morning thought to induce wakefulness and alertness.<\/td>\n<\/tr>\n
Melatonin<\/strong> (the sleeping hormone)<\/span><\/td>\nSecreted by the pineal gland.\u00a0 Plasma levels rise in the evening response to darkness, inducing sleepiness and maintaining the daily circadian rhythm.<\/strong><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

\"\"<\/a>
The normal synchronous relationships between sleep and daytime-activity and cortisol.
Hickie, I, Naismith, S., Robillard, R, Scott, E, Hermens, D. (2013). BMC medicine. 11. 79. 10.1186\/1741-7015-11-79<\/em>.<\/figcaption><\/figure>\n

Disease, Disorder, and Syndrome – What is the Difference?<\/strong><\/span><\/h3>\n

These three terms are sometimes used interchangeably, but they have distinct meanings:<\/span><\/p>\n\n\n\n\n\n
Disease<\/strong><\/span><\/td>\nA physiological or biological ailment either an underlying cause that may result in anatomical changes that are temporary or permanent.\u00a0<\/span><\/td>\n<\/tr>\n
Disorder<\/strong><\/span><\/td>\nAs defined by the National Institutes of Health (NIH):\u00a0 a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.<\/td>\n<\/tr>\n
Syndrome<\/strong><\/span><\/td>\nA cluster of various signs and symptoms that can vary over time and together suggest the presence of – or increased risk for – a particular disease.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

\"\"<\/a>
Woodcutting of a plague-stricken man lying in bed, attended by three physicians. From the Pestbuch, a 16th Century CE medical treatise by Hieronymous Brunschwig (c. 1450-1512 CE). (Courtesy of the Historical Medical Library of The College of Physicians of Philadelphia)<\/figcaption><\/figure>\n

Terms to Describe Duration,<\/span> Severity, and Stages of Disease<\/strong><\/span><\/h3>\n

Several important terms convey how quickly a disease develops, how severe it is, and how it progresses over time:<\/span><\/p>\n\n\n\n\n\n\n\n\n\n\n
Acute Onset<\/strong><\/span><\/td>\nSudden onset with severe symptoms.<\/td>\n<\/tr>\n
Insidious Onset<\/strong><\/span><\/td>\nGradual onset with mild symptoms that become more pronounced over time.<\/td>\n<\/tr>\n
Acute Illness<\/strong><\/span><\/td>\nA sudden, severe, and typically short-term illness.<\/td>\n<\/tr>\n
Chronic Illness<\/strong><\/span><\/td>\nAn illness lasting longer than 3 months, often starting with mild symptoms.<\/td>\n<\/tr>\n
Remission<\/strong><\/span><\/td>\nA period within a chronic illness when the person recovers somewhat and feels better.<\/td>\n<\/tr>\n
Relapse<\/strong><\/span><\/td>\nA period within a chronic illness when the disease worsens.<\/td>\n<\/tr>\n
Subacute<\/strong><\/span><\/td>\nNot as severe as acute illness and shorter than a chronic illness (sub- = below\/less)<\/td>\n<\/tr>\n
Subclinical<\/strong><\/span><\/td>\nEarly stage of disease in which no signs or symptoms are present; detectable only by sensitive and specific tests (e.g., imagining, or lab tests)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
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\nA Note on Chronic Pain<\/strong><\/p>\n<\/header>\n

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Current literature suggests that chronic pain<\/strong> is not always proportional to biological or physiological damage.\u00a0 In some cases, damage exists without pain; in others, pain persists after the damage has been resolved.\u00a0 Many internal and external factors contribute to chronic pain and treatment is therefore highly individualized, potentially involving physical rehabilitation, lifestyle strategies, and therapeutic counselling.<\/p>\n<\/div>\n<\/div>\n

Latent Stage, Incubation Stage and Prodromal<\/span> Period<\/span><\/strong>\u00a0<\/span><\/strong><\/span><\/h3>\n

These terms are closely related and are often confused.\u00a0 The key is to distinguish between infections and non-infectious scenarios, and to understand what each stage begins and ends with.<\/span><\/p>\n\n\n\n\n\n\n\n
Subclinical<\/strong><\/span><\/td>\nNo signs or symptoms; disease is present but undetectable by routine exam<\/td>\n<\/tr>\n
Incubation Stage<\/strong><\/span><\/td>\nApplies only to infectious disease<\/strong>.\u00a0 Begins when the pathogen enters the body; end with signs and symptoms<\/strong> develop.<\/td>\n<\/tr>\n
Latent Stage of Infectious Disease<\/strong><\/span><\/td>\nBegins when a pathogen enters the body; ends when the person becomes infectious (contagious)<\/strong>.\u00a0 Most often overlaps with the incubation stage.<\/td>\n<\/tr>\n
Latent Stage of Non-Infectious Disease<\/strong><\/span><\/td>\nBegins with the start of the disease (e.g., the first cancerous cell); ends when the disease becomes detectable by testing<\/strong>.<\/td>\n<\/tr>\n
Prodromal<\/strong><\/span><\/td>\nThe first time<\/strong> that signs or symptoms of illness are noticed (e.g., a scratchy throat at teh onset of a cold or flu).<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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\"Graph<\/a>
Four Stages of Infection: All infections (localize and systemic) go through four stages. The first stage known as the Incubation Period begins when a pathogen enters the body and ends when a person begins to show signs and symptoms. The incubation period typically lasts 1-3 days and is characterized by pathogen amplification (by multiplying) and spread to affect many cells. The incubation period often overlaps with the Latent Period, which also begins once the pathogen has successfully adhered to host cells. Latency is said to end when the person becomes infectious and is capable of spreading the pathogen to other hosts. The next stage is the Prodromal Stage which is characterized by the initial appearance of mild or vague symptoms. The third stage is termed Illness and is when a person experiences signs and symptoms related to the damage being caused by the pathogen along with the effects of the immune system’s response. The period of Convalescence is characterized by healing and recovery and coincide with the diminishment of pathogen particle numbers in the body as well as the fading out of signs and symptoms.<\/figcaption><\/figure>\n
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Real-World Application:\u00a0 COVID-19 and Silent Spreaders<\/strong><\/p>\n<\/header>\n

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Studies of SARS-CoV-2 (COVID-19) viral infections revealed an important distinction.\u00a0 While the incubation stage<\/strong> often directly overlaps with the latent stage<\/strong> of an infection, it was found that with COVID-19, the infectious stage can occur before<\/strong> signs and symptoms develop.\u00a0 This means the latent stage can end<\/strong> and the infectious stage can begin while a person still appears healthy – a phenomenon known as ‘silent spreading’.<\/strong>\u00a0 This differs from most respiratory infections such as colds and flu, where the infectious stage coincides with the appearance of symptoms like a runny nose and coughing.<\/p>\n<\/div>\n<\/div>\n

\"Example<\/a>
Mary Mallon, nicknamed “Typhoid Mary”, worked as a household cook for several New York families between 1897 and 1907. She was an asymptomatic “silent” carrier of Salmonella typhi, the pathogenic bacterium that causes typhoid fever. Due to her subclinical infection (an infection that caused few\/no signs), she infamously infected up to fifty-seven people, leading to three confirmed deaths. In the middle of this time period, she was forced into quarantine at Riverside Hospital and upon release was not permitted to return to cooking as a career – a promise which she did not adhere to resulting in twenty-five of the cases and two of the deaths. Her case continues to raise ethical questions about the protection of individual liberty, the safe-guarding of public health, and the treatment of infected individuals in both the courts and in public media. Salmonella typhi can cause a persistent subclinical infection of the gallbladder and exhibits fecal-oral transmission. This case also illustrates the importance of access to modern indoor plumbing, clean water and sanitation. (New York American (1909)).<\/figcaption><\/figure>\n

The Four Stages of Infection<\/strong><\/span><\/h3>\n

All infections – localized and systemic – progress through four stages:<\/p>\n\n\n\n\n\n\n
Incubation Period<\/strong><\/span><\/td>\nBegins when a pathogen enters the body; ends when signs and symptoms appear.\u00a0 Typically lasts 1-3 days; characterized by pathogen amplification and spread.\u00a0 Often overlaps with the Latent Period.<\/td>\n<\/tr>\n
Prodromal Stage<\/strong><\/span><\/td>\nCharacterized by the initial appearance of mild or vague symptoms.<\/td>\n<\/tr>\n
Illness<\/strong><\/span><\/td>\nThe person experiences signs and symptoms related to damage caused by the pathogen and the immune system’s response.<\/td>\n<\/tr>\n
Convalescence<\/strong><\/span><\/td>\nRecovery and healing, coinciding with diminishing pathogen numbers and the fading of signs and symptoms.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Local vs. Systemic:\u00a0 Where Does is Affect the Body?<\/strong><\/span><\/h3>\n\n\n\n\n
Local<\/strong><\/span><\/td>\nOnly a specific, discrete area of the body<\/strong> is affected (e.g., a localized wound or infection).<\/td>\n<\/tr>\n
Systemic<\/strong><\/span><\/td>\nThe illness affects the whole body<\/strong> (e.g., a fever or hypertension, which affects blood pressure throughout the entire body).\u00a0 A fever that heats up the whole body is another example.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Complication, Sequelae, and Convalescence<\/strong><\/span><\/h3>\n

As a disease progresses, additional complications may arise.\u00a0 It is important to distinguish between a complication and a sequela:<\/p>\n\n\n\n\n\n
Complication<\/strong><\/span><\/td>\nThe development of further negative conditions<\/strong> arising from the original illness (e.g., a heart attack results in the formation of a blood clot that travels to an organ depriving it of blood flow).<\/td>\n<\/tr>\n
Sequelae<\/strong><\/span><\/td>\nPermanent or long-term impairment<\/strong> resulting from a disease or complication – from the Latin word sequi,<\/strong> meaning ‘follow’ (e.g., kidney failure following poorly managed diabetes; or paralysis following a stroke).<\/td>\n<\/tr>\n
Convalescence<\/strong><\/span><\/td>\nThe period of recovery<\/strong>, which may involve rehabilitation exercises, speech therapy, improved mobility strategies, or other lifestyle changes.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
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Examples of Sequelae<\/strong><\/p>\n<\/header>\n

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Chronic Example – Diabetes:<\/strong>\u00a0 If diabetes is poorly managed over time, permanent biological damage can accumulate in blood vessels throughout the body.\u00a0 Common complications of vascular damage include chronic kidney disease, which may lead to kidney failure, requiring dialysis and placement on a transplant waiting list.\u00a0 Kidney failure<\/strong> in this context is a sequela<\/strong> of diabetes.<\/p>\n

Acute Example – Stroke (CVA, cerebrovascular accident):\u00a0<\/strong> A stroke affecting the left cerebral hemisphere in the frontal lobe may result in paralysis on the right side of the body.\u00a0 Some recovery is possible depending on stroke severity and treatment, but some paralysis<\/strong> is often permanent – this is a sequela.<\/strong><\/p>\n

Mental Health Example – PTSD:\u00a0<\/strong> Post-Traumatic Stress Disorder (PTSD) can develop following trauma (e.g., soldiers returning from war).\u00a0 If it becomes a long-term or permanent mental health impairment, it is considered a sequela of the trauma.\u00a0 Encouragingly, individualized and emerging treatments offer pathways to recovery.<\/p>\n<\/div>\n<\/div>\n

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\"Example<\/a>
Convalescence is the period following illness, injury, or surgery during which the body recovers and may require changes in lifestyle. During convalescence following a total knee replacement, patients are encouraged to walk to aid in the healing process.<\/figcaption><\/figure>\n

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