Pathophysiology - Exam 1

Pathology

The study of disease and focuses on both structural and functional changes

What are the different subspecialies of pathology?

Anatomic, surgical, and clinical

Anatomic pathology

examination of organs and tissues (e.g., autopsies)

Surgical pathology

Analysis of tissue samples from living patients

Clinical pathology

Evaluation of specimens such as blood or urine

Pathophysiology

The study of abnormal functioning of diseased organs. It directly applies medical procedures and patient care, focusing on progression of disease and clinical manifestation

disease

any structural or functional change that disrupts homeostasis and harms the body

principle of cellular pathology

all diseases originate at the cellular level, progressing to tissue and organ injury

Allopathic medicine / biomedicine / western medicine

standard modern medical practice

Pathogenesis

the sequence of events leading from structural or functional abnormalities to clinical manifestations, beginning at the cellular, biochemical, and molecular levels.

Different cause classification of diseases - Etiology (cause of disease)

• Identifiable - a specific cause is known, such as a pathogen.

• Multifactorial - multiple causes (e.g., genetic predisposition + environmental trigger).

• Idiopathic - cause unknown.

Etiology (Cause of Disease)

1. Genetic – inherited defects in structure or function

2. Developmental (congenital) - disorders prevent at birth due to abnormal intrauterine environment (ex. fetal alcohol syndrome)

3. Acquired - develops later in life. Causes may be:

   1. Exogenous (external) - infections, trauma, burns, radiation, chemicals, poor nutrition

   2. Endogenous (internal) - vascular, immunologic, or metabolic disorderes

Nosocomial disease

infection acquired in a healthcare setting.

Iatrogenic disease

caused by medical treatment.

Idiopathic disease

unknown cause.

Morphologic changes

structural abnormalities (gross or microscopic). These are central to diagnosis but have limitations since different diseases can appear similar.

Functional changes

abnormal function without visible structural lesions (common in early disease stages)

Clinical Manifestations

• Signs - objective findings (fever, abnormal pulse, pallor).
• Symptoms - subjective complaints (pain, dizziness, itching).
• Syndrome - a set of signs and symptoms that occur together.
• Findings - results from lab tests, imaging, or surgery

Timing of Disease

• Acute - rapid onset, short duration (e.g., flu, measles).
• Chronic - long duration, often progressive (e.g., arthritis, hypertension).
• Insidious - gradual, subtle onset.
• Terminal - inevitably results in death

States of Disease

• Preclinical - not yet apparent but will progress.
• Clinical - signs and symptoms evident.
• Carrier - harbors pathogen without being ill but can transmit disease

Outcomes

• Complication - secondary condition (e.g., kidney failure from diabetes).
• Sequela - long-term consequence (e.g., paralysis after polio).
• Mortality - measure of death due to disease.
• Morbidity - measure of disability.

Epidemiology

Study of disease occurrence in human populations

• Prevalence - total number of cases at a given time (useful for chronic diseases).

• Incidence - number of new cases over a period (useful for acute diseases).

• Risk factors - conditions that increase likelihood of disease.

• Cohort - group of individuals sharing a risk factor

Patient Evaluation

1. History of Present Illness – severity, onset, character of symptoms.

2. Medical History – past conditions that may affect current illness.

3. Family History – inherited risk factors.

4. Social History – occupation, habits, lifestyle, cultural context.

5. Review of Systems – additional symptoms not previously mentioned.

Physical Examination

Systematic assessment, correlating findings with history.

Differential Diagnosis

• Consideration of multiple possible diseases.

• Narrowed by lab tests, imaging, and specialist consultation.

Diagnostic Testing

• Screening tests - detect disease early.

• Laboratory tests - urinalysis, blood work, cultures, cytology.

• Imaging - CT, MRI, ultrasound, nuclear medicine.

• PCR testing - detects genetic material (e.g., viral infections).

• Biopsy - tissue analysis for definitive diagnosis.

Diagnosis

Based on history, physical exam, and test results.

Provisional diagnosis

initial conclusion when definitive diagnosis is uncertain.

Specific treatment

targets the disease directly.

Symptomatic treatment

relieves symptoms, improves comfort.

Prognosis

• Predicted course and outcome of the disease:

  • Chances of recovery

  • Potential for permanent impairment

  • Probability of survival

• Follow-up - monitoring progress

Evidence-Based Practice

The use of the best available research evidence, combined with clinical expertise and patient
values, in making decisions about patient care.

What are cellular adaptations and why are they important?

Adaptations are reversible responses that allow the cell to achieve a new steady state, enabling it to continue functioning despite stress.

What kinds of stimuli can trigger cellular adaptations?

Adaptations occur in response to normal physiologic stimuli (e.g., pregnancy) or pathologic stimuli (e.g., disease or injury).

What types of changes do cells undergo during adaptation?

Cells undergo functional and structural changes that help them survive and maintain function under stress.

What happens if the stress causing adaptation is removed?

The cell can return to its original state and recover.

What occurs if a cell cannot adapt to stress?

Cellular injury results, which can lead to either irreversible injury (cell death) or reversible injury if the stress is removed quickly enough and does not exceed the cell’s recovery capacity.

What are adaptive responses in cells?

They are mechanisms that enable the cell to cope with injury.

At what level do adaptive responses promote cellular changes?

They occur through changes in function at the level of the gene.

Can all cells adapt equally to stress or injury?

No, not all cells can adapt — some cells are more vulnerable than others.

Alternative Metabolism

Cell’s ability to employ alternative metabolic pathways to adjust to certain conditions

• Ex.

  • In hypoxic situations, cell adapts by switching to glycolysis (anaerobic respiration) to make ATP

  • Breaking down proteins and fats for energy if glucose levels are low

Organelle Changes

Ability of organelles to respond to changes in the cellular environment

• Ex.

  • Smooth Endoplasmic Reticulum (SER)

    • Increased synthesis of SER and associated enzymes when exposed to toxic
      chemicals

    • Enhances drug metabolism

    • Can lead to drug resistance

  • Mitochondria

    • Increase in number within skeletal muscle when energy demand rises

What are the different cellular responses to stress?

• Atrophy

• Hypertrophy

• Hyperplasia

• Metaplasia

• Dysplasia

What is hypertrophy and when does it occur?

Hypertrophy is the process of cell enlargement that occurs in response to increased demands and/or hormone signaling.

What causes the enlargement of cells during hypertrophy?

Enlargement is due to an increase in protein synthesis.

What happens to the functional components of the cell during hypertrophy?

There is an increase in the functional components of the cell.

How does hypertrophy improve the cell’s capacity?

The cell makes more enzymes and ATP, which increases its functional capacity.

What is an example of physiologic hypertrophy?

Muscle enlargement after weightlifting.

What is an example of pathologic hypertrophy?

Cardiac hypertrophy caused by hypertension.

What is hyperplasia and how does it occur?

Hyperplasia is the formation of new cells by mitosis in response to a stimulus.

In what types of tissues can hyperplasia occur?

It can only occur in tissues with cells capable of performing mitosis. (neurons and cardiac myocytes cannot)

How is hyperplasia related to hypertrophy?

• Hyperplasia frequently occurs together with hypertrophy.

  • Cells capable of division may undergo both hypertrophy and hyperplasia.

  • Cells with limited capacity to divide (e.g., cardiac or skeletal muscle) undergo hypertrophy only.

What are examples of physiologic hyperplasia?

• Uterus during pregnancy

• Compensatory hyperplasia after liver lobe removal

• Liver regeneration

What are examples of pathologic hyperplasia?

Overstimulation of hormones or growth factors.

Why is hyperplasia clinically significant in some cases?

Hyperplasia can predispose to neoplasia — for example, endometrial hyperplasia can lead to endometrial cancer.

How do cells that are capable of division respond to st

Cells that can divide respond to stress by undergoing hypertrophy (increasing in size) and hyperplasia (increasing in number).

How do cells with limited ability to divide, such as cardiac or skeletal muscle, respond to stress?

Cells with little capacity to divide, like cardiac or skeletal muscle cells, respond to stress mainly by hypertrophy, meaning they grow in size but not in number.

What is atrophy and what causes it?

Atrophy is the shrinking of the cell caused by factors that reduce the demand or adverse environmental conditions.

How do cells adapt when demand is reduced?

Cells adapt by gradually shutting down their specialized functions, decreasing protein synthesis, and reverting to a low level of activity that sustains only basic needs of the cell.

What happens to organelles during atrophy?

Organelle numbers are decreased by degrading them with lysosomal enzymes through autophagosomes.

What are the different types of pathologic atrophy?

• Disuse atrophy

  • Caused by reduced workload

• Decrease in nervous input

  • Ex. skeletal muscle without nervous stimulation

• Decrease in hormonal simulation

  • Seen in hormone responsive tissue

• Decrease in blood supply (ischemia)

  • Decreased oxygen and nutrients to the cell

  • May progress to irreversible injury and cell death

• Inadequate nutrition

  • Cachexia - Muscle wasting from loss of protein

  • Pathologic state of weight loss and anorexia

  • Seen in chronic infection and neoplasia

• Pressure atrophy

  • Shrinking of cels from long term application of pressure

What is metaplasia and what causes it?

Metaplasia is the conversion of one cell type to another, usually a more resistant type, resulting from chronic irritation or inflammation.

How does metaplasia occur, and what are its limits?

Metaplasia does not occur from a change in already differentiated cells but from the “reprogramming” of stem cells. The new cell type stays within the boundary of the original tissue type—for example, epithelial cells becoming a different epithelial cell.

What are the functional consequences of metaplasia?

Metaplasia usually leads to reduced function of the cell and an increased propensity to form neoplasia.

What is dysplasia and how are the cells characterized?

Dysplasia is when cells are disorganized and variable in size and shape, also called pleomorphic cells.

Under what conditions is dysplasia usually seen, and is it reversible?

Dysplasia is usually seen in epithelial tissue with severe, chronic irritation. It can be reversible, but less so than metaplasia.

Give an example of dysplasia and explain its significance.

An example is chronic bronchitis due to cigarette smoking. Dysplasia may precede tumors, making it precancerous.

What factors help determine cellular response?

• Specific stress

• Causative agent

• Duration, intensity

• number of exposures to it

• The type of cell ability to regenerate

What are the different causes of cell injury?

• Chemical agents and drugs

• Physical agents

• Biologic Agents

How can the immune system contribute to cell injury? (chemical agents and infectious drugs)

Immunologic reactions such as autoimmune diseases and hypersensitivity reactions can cause cell injury.

How do genetic and nutritional factors cause cell injury? (chemical agents and infectious drugs)

Genetic derangements and nutritional excess or deficiency, such as iron deficiency leading to anemia, can result in cell injury.

What are some examples of physical agents?

• Mechanical trauma

• Temperature extremes

• Atmospheric pressure changes

• Electrical shock

What are some examples of chemical agents and drugs?

• Glucose and ion imbalances

• Hyponatremia - cell swells

• Poisons - dose/time dependent

• Trace amounts of arsenic or cyanide can cause damage in minutes

• Environmental pollutants or alcohol - can take longer times

What are examples of biologic agents?

• Parasites

• Fungi

• Bacteria

• Viruses

• Prions

What is the most common cause of cell injury, and what does it do to the cell?

The most common cause of cell injury is hypoxia. It deprives the cell of oxygen, which interrupts oxidative metabolism and ATP generation

What is a key result of hypoxic cell injury?

Hypoxic cell injury leads to acute cellular swelling (edema).

How does the length of hypoxia affect cell injury?

The longer hypoxia lasts, the greater the chance of irreversible injury.

Which cells are most vulnerable to hypoxia, and why?

Cells with high metabolic demand—such as those in the heart, brain, and kidney—are most susceptible.

How soon can permanent brain damage occur after oxygen deprivation?

Permanent brain damage can occur within 4–6 minutes of oxygen deprivation.

How does reduced oxygen affect ATP production in the cell?

Reduced oxygen leads to decreased ATP synthesis, causing the cell to switch to anaerobic metabolism, which produces less ATP, increases lactic acid, and lowers pH.

What are the effects of low pH on the cell?

Low pH causes membrane damage and reduces cell size and function.

How does decreased ATP affect ion balance, and what structural changes result?

Decreased ATP causes failure of the Na⁺/K⁺ pump, leading to sodium and water influx, cell swelling, and vacuole formation as the ER membrane surrounds the water, making the cell appear paler.

Under what condition is hypoxic cell injury reversible?

Hypoxic cell injury is reversible if oxygen is restored in time.

What are the possible outcomes of hypoxic cell injury?

The outcomes are either adaptation or death, depending on the severity of the injury.

How do narrowed and occluded arteries differ in their effects on cells?

if an artery narrows, blood supply decreases and atrophy occurs. If an artery occludes, it leads to cell injury and death.

What is necrosis?

The structural changes that occur following cell death

How does the immune system respond to necrosis?

Necrosis triggers white blood cells to invade the area and digest debris through phagocytosis.

What local effects result from necrosis?

Necrosis causes local inflammation and cell death.

How are necrotic cell contents cleared, and what follows this process?

Cell contents are broken down by endogenous lysosomal enzymes and enzymes from invading cells. The debris is removed, and healing begins.

How is cell membrane damage detected clinically?

When the cell membrane is damaged, intracellular proteins leak into the blood, which can be measured to detect tissue-specific cell death.

What is an example of this clinical application of cell death detection?

troponin, a component of the contractile system in muscle tissue, escapes and can
be detected in blood-indicates Myocardial injury

What are the different types of necrosis tissue?

• Coagulative

• Liquefaction

• Caseous

What happens to the architecture of dead tissue in coagulative necrosis?

The architecture of dead tissue is preserved for days, and the tissue has a firm texture.

What type of injury is coagulative necrosis most characteristic of?

It is characteristic of hypoxic injury.

What is the most common cause of coagulative necrosis, and what tissue is the exception?

The most common cause is ischemia from vessel obstruction, with the brain being the exception.

What is an infarct, and how does its pattern form?

An infarct is a localized area of coagulative necrosis, and its pattern corresponds to the arterial blood supply.

What happens to tissue in liquefaction necrosis?

There is rapid breakdown of tissue without coagulation, and the tissue becomes a liquid mass.

Where is liquefaction necrosis commonly seen after an ischemic event?

It is common in brain tissue post-ischemic event.

How does liquefaction necrosis differ from coagulative necrosis?

Unlike coagulative necrosis, the tissue does not maintain structure but breaks down into a liquid mass.

Besides ischemic injury, what else can cause liquefaction necrosis?

It can also be seen in some bacterial infections.