Pathophysiology

• Involves the study of the structural (physical) or functional changes in the body that result from disease processes.

Pathophysiology Structure

• The Adult human is composed of about 75 trillion cells organized to form the tissues, organs and body systems.
• The body's fine performance record is due to its ability to maintain Homeostasis.

Homeostasis

• The maintenance of the stable internal environment.

• In order for an individual to servive, he must be able to adapt/adjust to changes in the internal and external environment.

Homeostatic Mechanisms

• Negative Feedback Mechanism
• Postive Feedback Mechanism

Negative Feedback Mechanism

• Stabilizing
• Example:  Blood sugar

Positive Feedback Mechanism

• Stimulatory (not as common)
• Example:  Blood clotting

Compensatory Mechanisms

• The body is compensating
• Example:  An athlete develops an abnormally high RBC count to meet his increase need for O₂.

Disease

• Sometimes, Homeostatic Mechanisms are unable to restore the steady state.
• The stress (significant changes in the internal or external environment) may lead to a malfunction of the body, which can cause Disease or even Death.

Disease conclusion

• May be defined as a deviation from the person's normal state of health
• Including physical, mental and social well-being
• Described as a disorder in structure, function, or both.

Disease usually invloves changes at a:

1. Organ or System level GROSS (seen by naked eye)
2. Cellular Level Microscopic

• Cells have mechanisms that allow them to adapt to altered conditions in the body
• These adaptations would permit survival and maintenance of function.

Cellular Adaptation

Atrophy

• Definition at a Cellular Level:  Decrease in Size of cells
• Cause: Decrease in Work Load
• Example:  Disuse Atrophy
• Involves skeletal muscles when an extremity is immobilized in a cast for 6 weeks.

Cellular Adaptation

Hypertrophy

• Definition at a Cellular Level: Increase in cell size NOT number
• Cause: Term used to apply to an increase in size to meet increased functional demands.  Organ enlarges when it is required to do extra work.
• Examples:  Muscles of a body builder.  In response  to an increase in work activity the Skeletal Muscle Fiber will increase in size.

Cellular Adaptation

Hyperplasia

• Definition at a Cellular Level: Increased in the number of cells resulting from an increase in Mitosis
• Causes: Compensatory Hyperplasia
• Adaptive mechanism that enables certain organs to regenerate
• May occur to meet incerased demands of the body

Cellular Adaptation

Hyperplasia

Example: Liver

• Even with 70% removal of the Liver, reeneration is complete in a few weeks.
• This would involove "Hyperplasia" of the remaining Hepatocytes.
• Hormonal Hyperplasia
• Estrogen also increase the number of cells
• Example:  Endometrium- prepares the uterus for implantation

Pathological Hyperplasia

• Abnormal Proliferation
• Examples:  Tumor formation
• Endometrial Hyperplasia is the most common example. 
• Causes excessive menstrual bleeding.

Cellular Adaptation

Metaplasia

• Often called Atypical Hyperplasia
• Definition at a Cellular Level:  Refers to Abnormal Changes in the size, shape, and organization of mature cells.
• Cells are abmormal and have LARGER NUCLEI
• These cells can be transformed into malignant cells
  

Cellular Adaptation

Dysplasia

Example: Breast Biopsy

• Data indicates that Atypical Hyperplasia is a strong predictor of Breast Cancer development.
• Dysplasia would indicate a Malignancy; need to remove the tumor.

Cellular Adaptation

Anaplasia

• Refers to cells that are Undifferentiated and demonstrate a variation in nuclei and cell structure
• Basis for a Grading a Tumor
• Associate this term with Malignancies

Cellular Adaptation

Neoplasm

• Definition:  New Growth
• Commonly referred to as a Tumor
• Neoplasia: development of Neoplasms
• Cancer refers to a Malignant Neoplasm

Disease at a Cellular Level

• Sometimes the cell injury can be reversable and allow the cell to repair itself.
• If the damage is intense or prolonged, or depending on the cell type, the injury may result in the cell Death.

Cell Injury

Cellular Deficiency

• Lack of a substance necessary to the cell
• Metabolic Reactions require a great variety of specific chenmicals as well as a general need for energy (ATP).
• Any lack of thses substances interferes with cell function and there for may cause injury.

Cell Injury

Cellular Deficiency Ctd.

• Hypoxic Injury
• Ischemia:  Decreased blood supply to the cells
• Results in insufficient O₂ delivery to those cells (Hypoxia) with a reduction in Cellular Metabolism
• Single most common cause of cellular injury
• Heart attacks and strokes are caused by O₂ and nutrient deficiencies in critical organs.
  

Cell Injury

Cellular Deficiency Ctd...

• Starvation: Involves a lack of dietary energy sources.
• Or the diet may be ample, but it lacks a specific nutrient and cell injury occurs
• Genetic Defects: Many substances in the cell's metabolic pathways are encoded in the Chromosomes.
• Damage to our chromosomes, may result in a decline in the production of specific enzymes and cell formation is comprised by this deficiency.

Cell Injury

Cellular Trauma

• Trauma is Physical Injury
• Inability of the cell to maintain homeostasis in the face of some type of injurious stimuli
• In some cases the physical damage is so great that the cell's integrity is completely lost as its Cell Membrane ruptures and its contents are lost

Physical Agents that Cause Cellular Trauma

Hypothermia

• Extreme cold injures cells as a result of ice crystal formation in the water of the cytoplasm.
• This kind of damage is typical of Frost Bite
  

Physical Agents that Cause Cellular Trauma

Hyperthermia

• Extreme heat damages cells by disrupting and coagulating proteins
• Such denaturing of protiens is characteristic of Burns.

Physical Agents that Cause Cellular Trauma

Radiation

• Disrupts the cell's Nucleic Acids, especially DNA
• X-rays: Leukemia is an occupational hazard for Radiologists.
• Ultraviolet rays from the sun may cause Skin Cancer, especially in fair-skinned people.

Physical Agents that Cause Cellular Trauma

Mechanical Pressure

• Pressure applied to a body surface
• Pressure of a rapidly expanding Tumor can cause injurty to adjacent cells

Physical Agents that Cause Cellular Trauma

Microbiologic Injury

• Infection (definition): Invasion and multiplication of a Pathogen.
• Bacteria can cause physical damage by releasing potent Enzymes that can break up the CT that support the host's cells
• Viruses multiply within cells; they cause rupture of the cell membrane, which releases them to infect other cells

Cell Injury

Cellular Intoxication

• Poisoning: The presence of a substance that interferes with cell function.
• Toxins:
• Biological Toxins: Produced by microorganisms such as Bacteria during an Infection.

Cell Injury

Cellular Intoxication CTD...

• Toxins:
• Nonbiological (Chemical) Toxins:  Damaging effect may be the result of exposure to a substance that is not well tolerated by the body.
• Examples: Carbon Tetrachloride Fumes
• Suicidal Overdose of a Therapeutic Drug

Cell Injury

Cellular Intoxication CTD...

• Genetic Defects:  Inborn errors of Metabolism can lead to abnormal Metabolic Processes (Chemical Reactions).
• This altered Metabolism can lead to toxic accumulations of Lipids or Proteins that destroy the Cells.

Cell Death

• Apoptosis refers to programmed Cell Death; "Cell Suicide".
• A normal occurrence when cells:
• Develop abnormally or have genetic damage.
• Have been produced in excess.
• Are injured or worn out as with age.

Necrosis

• Refers to when a group of cells die in the body.
• Examples:
• Infarction: Term that applies to an area of dead cells resulting from lack of O₂
• Gangrene: Area of vecrotic tissue that has been invaded by Bacteria
  

Necrosis ctd.

• Necrotic Tissue can provide a good medium for microorganisms to grow.
• Time Frame: Specific cells die at different rates

Etiology

• Cause of disease.

Genetic Disease

• Implies a Genetic Basis for the disease.
• A normal Gene may Mutate (change) and become defective.
• More common: Genetic Diseases are transmitted by a Defective Gene from parent to offspring.
• Examples:  Hemophilia, Sickle Cell Anemia, and Color Blindness.

Congenital Disease

• Wide range of severity, from trivial to the fatal
• Birth Defects
• Present at birth or are detected later in infancy or childhood.

Cause of Congenital Defects may be Gentic, Development, or a combination of both

• Developmental: Abnormalities caused from changes in Uterus during Embryonic (first 8 weeks) and Fetal development.
• Example: Maternal Infections during Pregnancy: German Measles (Rubella)
• Use of certain drugs and/or alcohol
• Birth Accident/Injury

Aquired Disease

• Largest category of Etiology
• In these conditions, Genes and Development are normal, but other factors, encourtered later, produce Disease
• Examples: Tuberculosis, AIDS, Emphysema

Idiopathic Disease

• Cause of the Disease is Unknown
• Disease can only be treated symptomatically

Clinical Manifestations

• Clinical evidence or effects of disease
• Signs and Symptoms and Laboratory Abnormalities that are associated with a Disease process.

Sign

• Objective evidence of a disease
• Can See or Measure presence of disease
• Examples:  Rash, fever, BP, Bruise, Swelling

Symptom

• Subjective
• Can't see or measure; Felt by the patient.
• Examples:  Pain, dizziness, nausea.