Clinical Course of Diseases

• The lecture discusses the Clinical Course of diseases, stages of diseases, epidemiology and cellular adaptation, injury, and death.

Clinical Course

• Describes the evolution and behavior of a disease over time, which can be acute, subacute, or chronic.
• Acute diseases are relatively severe but self-limiting, appearing suddenly and worsening rapidly.
• Chronic diseases are continuous, long-term processes with possible exacerbation (aggravation of symptoms) or remission (decrease in severity and symptoms). They develop gradually and worsen over an extended time.
• Subacute diseases fall between acute and chronic, being neither as severe as acute nor as prolonged as chronic.
• Clinical courses can be divided, according to infectious disease severity, into clinical, preclinical, subclinical, healthy/passive carrier status, and active carrier stages.
• In the clinical disease stage, the disease manifests with signs and symptoms.
• The preclinical stage involves no clinically evident signs or symptoms, but the disease is destined to progress to clinical disease and can be transmitted.
• Subclinical diseases are not clinically apparent, are not destined to become clinically apparent, and may remain latent.
• Healthy or passive carrier status refers to individuals harboring an organism without infection, antibody response, or clinical manifestations.
• Active carriers are infected individuals who can transmit the disease, regardless of exhibiting signs and symptoms.
• Remission is when a person with cancer is in remission, and relapse refers to when the person's cancer comes back.

Epidemiology

• Epidemiology is the study of disease occurrence in populations and the extent of infectious disease spread.
• It also involves studying risk factors for multifactorial diseases like heart disease and cancer.
• Epidemiology looks for patterns among affected people, such as age, race, or lifestyle.
• Incidence: The number of new cases arising in a population in a specific time.
• Prevalence: The number of people (new and pre-existing) in a population with a particular disease at a specific point in time.
• An epidemiologist studies the epidemiology.
• Epidemiology focuses on studying infectious diseases but also all diseases in general but was previously focused on studying infectious diseases because that use to the more common.
• Risk factors like smoking and alcohol can cause diseases like heart disease and cancer.
• Epidemiology studies the relationship between patients lifestyles, ages, and diseases.

Morbidity vs. Mortality

• Morbidity statistics provide information about the functional effects/clinical course of a disease on a person's life over time.
• Mortality statistics provide the number of deaths in a certain disease during a specific period.
• The epidemiologist determines if a death is related to a disease.
• Morbidity means how much a disease affects people’s lives even if they don’t die from it.
• Mortality means how many people die from a disease in as specific population in a specific time.
• An example is someone with COVID symptoms that passes away after being hit by a car is not considered as mortality related to COVID due to the time that has passed being too length.

Cellular Adaptations and Responses to Stress

• Pathophysiology bridges basic sciences (chemistry, biology, anatomy, and physiology) with clinical medicine (diagnosis and treatment).
• Cells try to maintain a steady state called homeostasis.
• Cells encountering stresses or stimuli can undergo adaptive changes for survival and function, or undergo cell injury.

Types of Cellular Responses

• Adaptation: The reversible and adaptive response of cells to normal stimuli
• Cell Injury: Occurs when cells are unable to adapt to continuous stress
• Reversible: Mild and transient damage to the cells if they can adapt
• Irreversible: when stresses and stimuli are severe and progressive, the cell cannot adapt
• Necrosis: always pathologic; cell death that involves the structural breakdown of cells and tissues ( cellular auto digestion)
• Apoptosis: Can be physiologic or pathologic; programmed cell death
• It is important to know that The keyword between necrosis and apoptosis is programmed

Factors Influencing Adaptive or Injurious Changes

• Not solely dependent on stress nature and severity, but also other variables such as:

• Blood supply

• Cellular metabolism

• Nutritional status

• Cells adapt to demands by changing size (atrophy, hypertrophy), number (hyperplasia), and form (metaplasia).

• Irreversible or Reversible changes may or may not depend on the nature and severity of the stress but depends on other variables.

• Variables that can affect those changes are:

• Blood Supply - how much blood supply is reaching the cell

• Cellular metabolism - how does a cell produce energy

• Nutritional Status - If the cell is receiving enough nutrition

Homeostasis vs. Hemostasis

• Homeostasis maintains a steady state.
• Hemostasis includes hemoglobin, which carries blood.

Coronary Arteries and Fibrosis

• Coronary arteries surround and provide blood to the heart.
• Blockage leads to ischemia and then hypoxia.
• Fibrosis may insulate electrical wires by impeding transfer of electricity throughout the heart causing heart failure.

Physiological vs. Pathological Adaptations

• Physiological adaptations are responses to normal stimulation by hormones or chemical mediators, such as hormone-induced breast and uterus enlargement in pregnancy.
• Pathological adaptations are responses to stress that allow cells to modulate structure and function to escape injury.
• Physiological Adaptations are the normal adaptations of the cells.
• Pathological Adaptations are not normal or natural adaptations.
• Examples of Physiological Adaptations include pregnancy due to hormones or the thymus gland getting smaller with age, called atrophy.

Hypertrophy

• Hypertrophy increases cell and organ size, occurring in cells with limited division capacity like skeletal and cardiac muscle.
• Can be physiologic (e.g., uterus during pregnancy, weightlifters' muscles) or pathologic (due to disease).
• Pathologic hypertrophy is adaptive (e.g., myocardial hypertrophy due to hypertension) or compensatory (e.g., nephrectomy).
• It increases functional demand or is caused by growth factors or hormonal stimulation.
• An example of the body compensating with it already has problems is the heart muscle thickening due to high blood pressure.
• Compensatory hypertrophy means that the body is going to try and make up for failing systems, cells, or organs.

Hyperplasia

• Hyperplasia refers to increase in cell number in an organ or tissue.
• It occurs in tissues capable of mitotic division, such as the epidermis, intestinal epithelium, and glandular tissue.
• It may occur concurrently with hypertrophy and often responds to the same stimuli.
• It can be physiologic or pathological and the body does this thing so that is cant adapt to certain symptoms.
• Hyperplasia is a increase in the total replication of cells in general
• Hypertrophy is mostly focused on the replication of cells that can not replicate

Types of Physiological Hyperplasia

• Hormonal: proliferation of glandular epithelium in the female breast at puberty and during pregnancy, and uterine enlargements during pregnancy that results from estrogen stimulation).
• Compensatory: residual tissue grows after removal or loss of part of an organ (e.g. Liver).
• Pathologic hyperplasia is caused by excessive hormonal or growth factor stimulation.
• In endometrial hyperplasia cause abnormal menstrual bleeding.
• The hyperplastic process remains controlled process (differs from cancer), if the signals that initiate it stop, the hyperplasia disappears.
• A Key word for what to focus on that is different between physiological hyperplasia and cancer is that physiological stays as a controlled process
• Controlled process means that the body is controlling how the cells function compared to cancerous cell which do not know how or when to stop
• Examples would be when there is not enough of certain tissue, for example if someone is missing a organ, cells will replicate to attempt to compensate.

Skin Warts

• Skin warts are caused by a virus and cause raised skin.
• Possible treatments include asprin to dry them out.
• Also known as keratolytic

Atrophy

• Atrophy is cell shrinkage due to loss of cell substance, decreasing organ size.
• Atrophied cells have diminished function but are not dead.
• The atrophy has the person is still alive and well with the cells shrinking, they are still working less and less.
• Causes of atrophy include:
• Decreased workload (e.g., immobilization of limbs).
• Loss of innervation (e.g., paralyzed limbs).
• Diminished blood supply (ischemia).
• Inadequate nutrition (malnutrition).
• Loss of endocrine stimulation (e.g. menopause)
• Aging
• The mechanisms of atrophy consist of a combination of decreased protein synthesis and increased protein degradation in cells in addition to stimulation of autophagy ("self-eating") process.
• The mechanisms start decreasing the amount of protein they can eat while also simultaneously creating a simulation where they eat more protein. Examples.
• A broken leg and no muscle movement.
• Not eating enough causing the cells to go away and degrade.
• Getting older can cause cells to be injured in process and go away

Autophagy

• The cells are eating their nutrients just to sustain themselves.

Metaplasia

• Metaplasia is a reversible change in which one adult cell type is replaced by another adult cell type that have better ability to withstand the adverse environment.
• Metaplasia is thought to arise by reprogramming of stem cells to differentiate along a new pathway to produce the new more resistant type of cells.
• It occurs in response to chronic irritation and inflammation.
• Metaplastic cells have survival advantages, but lack some the specialized functions of the normal cells.
• Under prolonged effects of the stressful agent the metaplastic cells may be transformed to cancer cells
• Metaplasia cells are changing in terms of cell type but this is because the cells are adapting due to some type of outer stress.
• An example of this is a smokers' trachea and bronchi are lined by stratified squamous epithelial cells instead of normal columnar epithelial cells so that it can better adapt without damaging the lungs.
• Examples of how cells are able to transform.
• Changing how much cells are going back and forth.
• Changing the different properties so they can transfer easier.
• Changing the general makeup so that they cause the intended consequences.
• It is important to think of cellular cells changing so that they can best affect the external symptoms
• Cilia which is located in bronchioles produces mucous that helps capture the harmful toxins. Smoker causes a change to the shape of the cell which results in higher chances of not being able to push as much waste outside of the lungs.