Patho Exam 1 Review

• Pathology:

  • The study (logos) of disease (pathos , suffering).

• Investigation areas:

  • Causes of disease.

  • Level changes:

    • Cell

    • Tissues

    • Organs

  • These changes lead to presenting signs and symptoms.

• Physiology:

• Study of functions of living organisms.

• Pathophysiology:

  • Study of abnormalities in physiological functions.

  • Deals with responses to disruptions in homeostasis.

  • Focuses on common and classic presentations of disorders.

• General Pathology:

  • Cellular and tissue alterations caused by a pathological stimuli.

  • This is the basic, universal reactions that all cells and tissues have when something goes wrong.

  • Focuses on:

    • How all cells respond to injury

    • General processes like:

      • Inflammation

      • Cell injury & death

      • Wound healing

      • Neoplasia (new, abnormal growth)

• Systems Pathology:

  • Reactions and abnormalities of specialized organs.

  • Identify changes in response to injury

  • This is about specific organs or systems (heart, lungs, liver, kidneys) and how they react or fail when injured.

    • Focuses on:

      • Organ-specific diseases

      • Specialized reactions in that organ system

      • Example: heart attack (myocardial infarction), liver cirrhosis, kidney failure

• Etiology:

  • Origin of disease.

  • Underlying causes

  • Modifying factors.

  • Can be genetic or environmental.

• Study of the causes or reasons for the phenomena.

• Identify the causal factor:

  • Idiopathic (unknown cause)

  • Iatrogenic (caused by medical intervention)

  • Causative agent (e.g., bacteria, virus)

• Pathogenesis:

  • Steps in the development of disease.

  • How etiological factors cause:

    • cellular changes

    • molecular changes

    • structural and functional abnormalities characteristic of the disease

    • Development of clinical manifestations

• Clinical manifestations:

  • Observed as signs and symptoms:

    • Signs: Objective changes that a clinician can observe and measure (e.g., fever, rash).

    • Symptoms: Subjective changes in body functions that are not apparent to an observer (e.g., headache, nausea).

    • Syndrome: When etiology of signs/symptoms are not determined.

• Stages and Clinical Course

  • Latent or incubation period:

    • No recognition by patient.

    • Lab tests may detect the disease

  • Prodromal period/Prodrome

    • Appearance of first signs/symptoms (non-specific)

  • Manifest illness/Acute phrase

    • signs/symptoms at greatest severity

  • Subclinical phase:

    • Patient functions normally although disease is well established.

• Acute Condition

  • Severe manifestations for a short time (Hours to a few weeks)

• Chronic Condition

  • Lasts for months to years

  • Acute can become chronic or chronic can become acute

• Course of Diseases:

  • Exacerbations: Sudden increase in severity.

  • Remissions: Decline or abatement in severity.

  • Convalescence: Stage of recovery after disease, injury, or surgery.

  • Sequela: A condition that is the consequence of a previous disease or injury.

• Normal Distribution (bell-shaped curve):

  • 95\% of values fall within a normal range.

  • Estimates of diseases in a normal population are based on this curve.

• Reliability:

  • Ability of a test to give the same result in repeated measurements.

• Validity:

  • Degree to which a measurement reflects the true value of what it intends to measure.

• Predictive Value:

  • Extent to which the test can differentiate between the presence or absence of a condition.

    • Positive predictive value.

    • Negative predictive value.

• Sensitivity:

  • Probability that a test will be positive when applied to a person with a particular condition.

• Specificity:

  • Probability that a test will be negative when applied to a person without a particular condition.

• Epidemiology:

  • Study of patterns of disease.

  • Examines:

    • Occurrence

    • Prevalence

    • Transmission

    • Distribution among population

• Endemic disease:

  • Native to a local region.

  • Always present in a certain population (e.g., malaria).

• Epidemic disease:

  • Outbreak spreading rapidly/extensively through a population.

  • Affecting an atypically large amount of people within a population (e.g., smallpox, typhus).

• Pandemic disease:

  • Worldwide epidemic, spread to large geographic areas (e.g., polio in the 50’s, TB after WWI, AIDS, SARS).

Factors:

• Age: Developmental stages from maturity to post-maturity.

• Ethnic group: Sickle cell anemia vs. pernicious anemia.

  • Sickle cell:

    • Genetic blood disorder

    • Red blood cells = sickle-shaped

    • Causes pain, anemia, infections

  • Pernicious anemia:

    • Vitamin B12 deficiency

    • Body can’t absorb B12 (lack of intrinsic factor)

    • Causes fatigue, pale skin, numbness

• Gender:

  • Women: Endometriosis (uterine tissue outside uterus)

  • Men: Prostatic hyperplasia (enlarged prostate)

• Socioeconomic factors and lifestyle conditions: Obesity vs. malnutrition.

• Geographic location: Malaria, African sleeping sickness.

• Prevention levels:

  • Primary prevention: Preventing the disease to even happen, reducing exposure and lowering risk factors

  • Secondary prevention: Early detection, screening, and management

  • Tertiary prevention: Medical and surgical interventions, rehabilitation, supportive care, attempts to alleviate disability and restore function.

• Necrosis:

  • Cell death caused by external injury

  • Pathological (always bad)

  • Leads to significant tissue damage

  • Examples: burns, infections, lack of blood flow (ischemia)

• Apoptosis

  • Programmed cell death (cell suicide)

  • Controlled by intracellular signals

  • Can be normal (like during development) or pathological

  • No inflammation or tissue damage

• Reversible Cell Injury

  • Results in cellular swelling.

  • Accumulation of excess substances in the cell.

  • Due to cell inability to perform normal metabolic functions.

    • Lack of ATP.

    • Dysfunction of associated metabolic enzymes.

  • If acute stress or injury is removed, the cell returns to its pre-injury state.

• Hydropic Swelling

  • Due to accumulation of water.

  • First manifestation of reversible cell injury.

  • Malfunction of Na+/K+ pumps (lack of ATP).

  • Characterized by large, pale cytoplasm, dilated/swollen organelles.

  • Swelling of the organ is indicated by the suffix -megaly.

• Intercellular Accumulations

  • Can be toxic and provoke an immune response.

  • Occupy space needed for cellular functions.

  • Can be indicators, but not actual cause of injury.

  • Types:

    • Excessive amounts of intracellular substances

      • Lipids (e.g., Tay-Sachs, excess alcohol consumption).

    • Accumulation of abnormal substances produced by the cell due to faulty metabolism

      • Glucose converted to sorbitol then fructose.

    • Pigments or inorganic particles unable to degrade

      • Melanin, mineral dusts.

• Protein Accumulation

  • Cellular stress may lead to accumulation and aggregation of denatured proteins.

  • Abnormally folded intracellular proteins may cause dysfunction or death.

  • Chaperones (heat shock proteins) are responsible for binding and refolding proteins.

  • Ubiquitin targets abnormally folded proteins for degradation.

• Accumulation of Inorganic Particles

  • Can cause chronic inflammation in lungs.

  • Destruction of pulmonary alveoli.

  • Formation of scar tissue.

  • Calcification of heart valves and blood vessels.

  • Example: Accumulation of silicon dust in tissues of the lungs.

Cellular Adaptations

• Responses that allow cells to modulate structure and function.

• May not be beneficial to the cell.

• Common responses:

  • Atrophy: decrease in cell size.

  • Hypertrophy: increase in cell size.

  • Hyperplasia: increase in cell number.

  • Metaplasia: conversion of one cell type to another (potentially reversible).

  • Dysplasia: disorderly growth.

Atrophy

• Shrinkage in cell size by the loss of cell substance.

• Diminished in function, but not dead.

• Causes:

  • Decreased work load.

  • Loss of innervation or endocrine stimulation.

  • Diminished blood supply (ischemia).

  • Inadequate nutrition.

  • Persistent cell injury.

  • Aging.

Mechanisms for Atrophy

• Combination of decreased protein synthesis and increased protein degradation.

• Pathways for protein degradation:

  • Ubiquitin-proteosome pathway.

  • Autophagy.

Hypertrophy

• Increase in cell size resulting in an increase in the size of the organ.

• Increase in cellular content.

• No new cells, just bigger cells.

• Can be physiological:

  • Response to growth factor or hormonal stimulation.

• Or pathological:

  • Enlarged heart due to high blood pressure or aortic valve disease.

Hyperplasia

• Takes place IF the tissue is capable of replication.

• May occur concurrently with hypertrophy.

• Results from increased physiological demands or hormonal stimulation.

  • Demand-induced hyperplasia:

    • Increase in RBC due to high altitude.

  • Hormonal hyperplasia:

    • Increase in estrogen à increase in endometrial cells.

  • Compensatory hyperplasia:

    • Residual tissue grows after removal or loss of part of an organ.

Metaplasia

• Reversible change in which one adult cell type replaces another.

• Usually, the second cell type can tolerate injury better.

• Involves reprogramming of stem cells.

• Example: Metaplasia of normal columnar to squamous epithelium in a bronchus.

Dysplasia

• Disorganized appearance of cells.

• Adaptive effort gone astray.

• Abnormal variations in size, arrangement, and shape.

• Regarded as neoplastic lesions.

• Significant potential to transform into cancer cells.

Irreversible Cell Injury

• Pathologic cellular death occurs when injury is too severe or prolonged.

• Leads to cell death.

• Two processes:

  • Necrosis.

  • Apoptosis.

• Differ in mechanisms, morphology, and roles in disease.

Necrosis vs. Apoptosis

• Necrosis:

  • Consequence of ischemia or toxic injury.

  • Characterized by cell rupture.

  • Contents spill into extracellular fluid, causing inflammation.

• Apoptosis:

  • Does not directly kill the cell but triggers intracellular cascades.

  • Activates cell suicide.

  • Does not rupture.

  • Ingested by neighboring cells.

  • No inflammation.

Necrosis and Intracellular Content Release

• Intracellular content released into the bloodstream.

• Elevated levels of certain proteins/enzymes can indicate the location of damage.

  • Elevated creatine kinase (MB isoenzyme) or cardiac troponin levels indicate myocardial damage.

Four Types of Tissue Necrosis

• Coagulative necrosis.

• Liquefactive necrosis.

• Fat necrosis.

• Caseous necrosis.

• Differ in the type of tissue affected.

Coagulative Necrosis

• Most common type.

• Manifestations are the same regardless of cause.

• Area composed of denatured proteins.

• Generally solid.

• General architecture persevered up to weeks.

• Example: Wedged-shaped kidney infarct.

Liquefactive Necrosis

• Dissolution of dead cells occurs quickly.

• Lysosomal enzymes dissolve tissues.

  • Brain:

    • Rich in degradative enzymes, little supportive connective tissue.

  • Bacterial or fungal infections:

    • Trigger accumulation of localized WBC, resulting in pus.

• Example: Infarct of the brain showing dissolution of tissue.

Fat Necrosis

• Death of adipose tissue.

• Results from trauma or pancreatitis.

  • Liquefy fat cells in the peritoneum.

• Visible white chalky areas.

• Example: Fat necrosis in acute pancreatitis in the mesentery.

Caseous Necrosis

• Cheesy appearance.

• Area is white, soft, and fragile.

• Dead cells walled off by inflammatory WBCs.

• In the center, dead cells lose their structure.

• Example: Tuberculosis of the lung.

Gangrene

• Cell death of a large area of tissue.

• Results from disruption of major blood supply.

• Affects toes, legs, bowels.

• Depending on appearance and subsequent infection:

  • Dry.

  • Wet.

  • Gas.

• May be fatal.

Apoptosis: Controlled Cell Death

• Rate of cell division and cell death are controlled in cells.

• If cells are not needed, cell suicide will occur.

• Activates a cell death pathway.

• Enzymes degrade the cell’s own DNA and proteins.

• Can be physiologic or pathogenic.

• Can be triggered by extrinsic or intrinsic signals.

Mechanisms of Apoptosis: Extrinsic Signals

• Withdrawal of survival signals that normally suppress the pathway.

  • Normal cells rely on environmental signals to stay alive.

  • Removing these signals activates the cell suicide cascade.

• Extracellular signals, such as Fas ligand (FasL).

  • Bind to cell à triggers death cascade through activation of “death receptors”.

  • Leads to DNA degradation and fragmentation of cell.

Mechanisms of Apoptosis: Intrinsic Signals

• Cellular damage causes cells to stall growth and division.

• If damage is too great à cell suicide.

• Mitochondrial damage:

  • Leakage of cytochrome c into the cytoplasm.

  • Activates intrinsic pathway.

  • p53 governs this pathway.

Etiology of Cellular Injury

• Variety of cellular assaults:

  • Lack of oxygen and nutrients.

  • Infection and immune responses.

  • Chemical, physical, and mechanical factors.

• Extent depends on duration and severity of assault and prior condition of cells.

Ischemic and Hypoxic Injury

• Ischemia:

  • Interruption of blood flow.

• Hypoxia:

  • Lack of oxygen resulting in power failure.

• Most common cause of cell injury.

• Allows metabolic wastes to accumulate.

• Deprives cells of nutrients for glycolysis.

• Reperfusion injury.

Nutritional Injury

• Deficiencies or excess amount of nutrients.

• Nutritional imbalances:

  • Deficiencies

    • Iron deficiency affects RBC.

    • Vitamin D deficiency affects bones.

  • Excess

    • Delivery to some cell types and not other cell types

    • Neurons uptake excess glucose.

Infectious and Immunologic Injury

• Bacteria and viruses.

• Either by directly or indirectly triggering an immune response.

Chemical Injury

• Toxic chemicals cause cell injury directly OR.

• Injurious only when metabolized into reactive chemicals in the body.

• Some toxins have an affinity for particular cell types.

  • Carbon monoxide to hemoglobin.

• Some toxins exert a widespread effect.

  • Lead poisoning.

Physical and Mechanical Injury

• Factors:

  • Extremes in temperature.

  • Abrupt changes in atmospheric pressure.

  • Mechanical deformation.

  • Electricity.

  • Ionizing radiation.

Cellular Aging

• Aging and disease are two different processes.

• Progressive decline in proliferative and reparative capacity of cells.

• Exposure to environmental factors.

• Causes:

  • U.V. radiation.

  • Oxidative stress.

  • Errors in replication.

  • Mutations.

  • Cell loss.

  • Accumulated metabolic cell damage.

Somatic Death

• Death of the entire organism.

• No inflammation or immunologic response occurs prior to death.

• General features include cessation of respirations and heartbeat.

• Rigor mortis:

  • ATP \rightarrow actin myosin cross bridging

• Postmortem autolysis:

  • Putrefaction.