Untitled

• Disease is a deviation in "normal" health.

Infectious vs. Non-Infectious

• Infectious diseases are caused by pathogens.
• Non-infectious diseases are not caused by pathogens.
• Idiopathic diseases have an unknown cause.
• Iatrogenic diseases arise from the treatment of another disease, like drugs with side effects.

Acute vs. Chronic

• Acute diseases are short term, go away quickly.
• Chronic diseases are long term, last a lifetime, and develop slower.

Diagnosis vs. Prognosis

• Diagnosis occurs before treatment and focuses on the past.
• Prognosis is future-focused and follows treatment.

Remission vs. Exacerbation

• Remission means the disease is gone for a short or long term.
• Exacerbation means the disease is worsening.
• Complications are problems that arise during treatment.
• Sequelae are complications that occur because of treatment, like a scar.
• Predisposing (Risk) Factors make someone more susceptible to a diseases; such as smokers and lung cancer.
• Clinical Manifestations are signs vs symptoms.

Signs vs. Symptoms

• Signs are objective, like a fever or rash.
• Symptoms are subjective, like pain or a stomach ache.

Local vs. Systemic

• Local affects one part of the body.
• Systemic affects 2 or more parts of the body.

Epithelial vs. Connective Tissues

• Epithelial tissues have cells packed closely together with not much space between cells.
• Connective tissues have cells spread farther apart with more space in between cells such as blood, bones, tendons and ligaments.
• Cells in the body may be normal, injured, or adapted.
• Adapted cells have not suffered injury but accommodate to the body and goes back to normal when done.

Cellular Adaptation - Atrophy

• Atrophy is a decrease in cell size.

Cellular Adaptation - Physiologic vs. Pathologic Atrophy

• Physiologic atrophy is not part of a disease process; such as the thymus.
• Pathologic atrophy is part of a disease process.
• Disuse Atrophy happens using muscle tissue because of lack of use.

Cellular Adaptation - Hypertrophy

• Hypertrophy is an increase in cell size.
• Physiologic hypertrophy
• Pathologic hypertrophy

Cellular Adaptation - Hyperplasia

• Hyperplasia is an increase in cell number.
• Physiologic hyperplasia
• Pathologic hyperplasia
• Compensatory Hyperplasia: an organ / tissue size or cell number changes to compensate for loss / damage of another tissue.
• Hormonal Hyperplasia: excessive growth of cells due to hormonal imbalance.
• Metaplasia = Cellular replacement; using a less mature cell which is reversible, and it is a normal process.
• Dysplasia is abnormal changes in cells:
  • Atypical hyperplasia is an abnormal increase in cell number
  • Neoplasia is uncontrolled, abnormal growth of cells
  • Cancer

Cellular Adaptation - Causes

• Increase or decrease in workload and blood supply
• Changes in nutrition and hormones such as hormone concentrations
• Nervous system stimulation, or lack thereof
• Causes may be direct or indirect and normal or part of a disease process (physiologic versus pathologic).

Cellular Injury

• There are reversible and Irreversible Injuries.
• Reversible Injuries can go back to normal with or without injury.
• Irreversible Injuries cannot go back to normal.
• The "point of no return" for injured cell = the cell is unable to return to normal and necrosis occurs.

Features of Injured Cells

• Severe drop in ATP production
• Water flows into cell en masse causing extensive vacuolation, especially in mitochondria.
• Oncosis (a.k.a. hydropic degeneration):
  • Cells store water and compartmentalize it, but try to get it out of cell
• High Ca2+ infiltration into the cell
• Accumulation of oxygen-derived free radicals
  • Antioxidant vitamins prevent this from occurring

Cellular Injury - Causes

• Hypoxia: insufficient oxygen to cells
• Anoxia: a cell completely lacks oxygen
• Usually results from ischemia: blood deprivation to tissue
• May result from asphyxial injury to tissues due to physical pressure
• Reperfusion injury may also occur when a tissue deprived of oxygen is flooded with oxygen again= excess free radical concentrations.

Cellular Injury - Free Radical Damage

• Atom(s) with unpaired electrons
• Reactive Oxygen Species (ROS): toxic oxygen free radicals
• Oxidative Stress: tissue injured due to overflow of oxygen
  • e.g. O2¯, OH, H2O2
• Chemical Injury: toxic chemical agents (xenobiotics) molecule that is not found in nature
  • Cyanide
  • Lead, CO, ethanol, drugs
  • Cyanosis occurs with skin turns blue due to oxygen deprivation.
• Infectious/Inflammatory Injury
  • Pathogens: Parasites that feeds off of host & harms the host
• Traumatic Injury
  • Blunt Force Injury: does not penetrate tissue (punch, kick).
  • Sharp force Injury: punctures tissue (knife).

Manifestations of Cellular Injury (Infiltrations)

• Water (vacuolation): cell takes water & stores it in vacuoles, so cell does not become too diluted.
• Lipids (fatty change): lipid build up in cells.
• Carbohydrates (glycogen accumulation): polymer of glucose.
• Proteins (melanin, hemoproteins, etc.).
• Calcium
  • Dystrophic Calcification: follows tissue injury since it happens following tissue damage.
  • Metastatic Calcification: calcification comes first, thus damaging tissue.
• Uric Acid (hyperuricemia, can lead to gout): too much uric acid in the bloodstream.

Cellular Death

• Necrosis is cellular changes that happen after death.
  • Autolysis: Diseased cell dies and bursts:
    • Check troponin levels to see if someone had heart attack.
  • Pyknosis: cell & its nucleus shrinks up but does not burst; sometimes, nucleus might lyse without the rest of cell.
  • Karyolysis is the dissolution of chromatin in a dying cell structure while Karyorrhexis is the breaking down of of a nucleus of a dying cell with its fragments.

Types of Necrosis

• Coagulative Necrosis (infarct): tissue dies in part or in whole.
• Liquefactive Necrosis: tissue dies & becomes liquified.
• Caseous Necrosis: cheese-like and happens because of infectious disease.
• Fat Necrosis (saponification): soap-like fat accumulation in tissues.
• Gangrenous Necrosis happens because of interruption in blood supply, with the tissue beginning of turn black.
  • Gas gangrene means bacteria build up because of lack/interruption in blood supply.
• Apoptosis is cellular "suicide" which initiates a self-destruct program and may happen in normal and diseased tissues.
  • Nucleus + cytoplasm shrink and results in fragmentation of a cell.

Inflammation and Wound Healing - First Line of Defense

• Non-specific defense that is not subject to activation/deactivation.
• Skin, chemical barriers: such as stomach acid, genes, microbiome creating a barrier of defense, and normal flora antagonizes pathogens.

Inflammation and Wound Healing - Second Line of Defense

• Non-specific defense that is activated as needed.
• Interferons, complement proteins.

Inflammation and Wound Healing - Third Line of Defense

• This is involved in specific immunity with B & T cells.
• Vaccines.
• Inflammation is a non-specific, localized response to injury = Redness, Swelling, Heat, Pain, and Loss of function.
• Acute versus Chronic Inflammation
• Acute inflammation
• Chronic inflammation

Exudate: Fluid that infiltrates area of inflammation

• Serous exudate: clear and water-like
• Fibrinous exudate: cloudy since it contains fibrinogen
• Purulent exudate (abscess): pus-like because it is made off bacteria
• Hemorrhagic exudate
• Granulomas is when the body tried to encapsulate so it does not spread largely due to degranulation of mast cells of basophils and neutrophils.
• Immediate response chemicals:
  • Histamine
  • Many WBC chemotactic factors attracting WBC to the area of the body where they are needed
• Long-term response chemicals:
  • Prostaglandins: Maintain inflammation for as long as needed.
  • Leukotrienes = lipid that don't start inflammation; interact W/ nervous system; send pain signals.
  • Aspirin.

Complement System

• Proteins in the blood that help the body fight infection.
• B cells makes antibodies used to defend the body against invaders.
• Clotting system is for hemophilia and platelets and prevents bleeding when a blood vessel is injured.

Three Main Phases Following Tissue Injury

• (1) Vasodilation (and ↑ tissue permeability)
  • Blood vessel diameter + In influx of exudate causes the increase of blood flow but the flow rate decreases because the tissue becomes more permeable to fluid.
• (2) Phagocyte migration/phagocytosis
  • Chemotaxis: when something is chemically attracted to something
  • Margination: WBC stick themselves to vessel walls
  • Diapedesis: Squeeze in between cells to get to area.
• (3) Repair of damaged tissues
  • Regeneration and Repair:
    • Regeneration: Minimal tissue damage; tissue can regenerate back to original structure & function
    • Repair: Tissue might not be made to what it was, resulting in the development of scar tissue.

Healing of Wound

• Reconstructive = Replace cells & Rebuilds tissue.
• Maturation = Restoring the Function; Body starts to adopt the function of cells around it
• Primary versus Secondary Intention = how you classify healing on wounds
  • Primary Intention = Tissue likely to regenerate
  • Secondary Intention = Tissue likely to to be replaced and repaired

Dysfunctions in Inflammation and Wound Healing

• Hypovolemia means vessel constriction; body constricts blood cells to stop you from losing too much blood.
  • Spleen releases reserve of cells.
• Excess bleeding = slower repair times
• Defects in collagen synthesis (in repair phases) due to excessive formation of collagen result in:
  • Hypertrophic scarring
  • Keloid formation: synthesis of collagen & fibers is excessive: more common on dark skin people
  • Genetic collagen synthesis defects: healing time is slow
• Dehiscence is the reopening of sutured wounds.
• Wound contracture is excessive contraction.

Immunodeficiency

• It is a defect in self-defense mechanism(s).
• There are primary versus secondary immunodeficiency.
  • Primary (Congenital) Immunodeficiency: where you are born with defect (usually genetic) = B-cells (e.g. agammaglobulinemia) and/or T-cells.
    • SCIDS is a Severe combined immunodeficiencies with rare genetic disorders that causes problems within the immune system
  • Secondary Immunodeficiency: where you contract after birth.
    • Nutritional, Iatrogenic, Trauma, Stress, and Infection disease such as HIV → AIDS.
• Treatments for Immunodeficiency: IVIg (and CPT), Stem cell/bone marrow grafts, and Gene therapy

Hypersensitivity

• Exaggerated response to (foreign/benign substance) that results in - Immediate versus Delayed Hypersensitivity:
  • Immediate = Comes on right away
  • Delayed = Takes weeks or days for symptoms to happen
  • Anaphylaxis = Histamine is dumped; causing vasodilation (swelling).
• Cutaneous Versus Systemic Anaphylaxis:
  • Cutaneous = Localized / Smaller reaction
  • Systemic = Severe / All over whole-body reaction = Impacts organs.
• Three Main Types:
  • (1) Allergy = Body responds to allergens that reacts in the body by a release of histamine.
• Neoantigens : foreign proteins that are absent in normal Tissues
  • (2) Autoimmunity = Immune system target itself (no tolerance) due to a Clonal deletion didn’t happen and Immune system targets self material that closely resemble foreign material
  • (3) Alloimmunity = Response from Grafted tissues:
    • Autograft (NO alloimmune response): graft from SELF
    • Isograft (NO alloimmune response): graft from identical twin
    • Allograft: graft from same-origin Species
    • Xenograft: graft from different-species.
• Acute rejection = Happens faster, over days/weeks;
• Chronic rejection happens over more time, usually several weeks to months
• Hyperacute Rejection = Transplant rejection over hours / Minutes.

Four Mechanisms of Hypersensitivity

• Type I Hypersensitivity: A food Allergy.
  • IgE causes most cell degranulation to release histamine.
  • Urticarial with a wheal and flare reaction.
• Atopy: (genetic predisposition) some people more prone to allergies than others.
• Desensitization for prevention via:
  • Blocking Antibiotics: IgG class and that keeps antigen away from IgE
• Type II Hypersensitivity is rejecting a grafted organ or a blood transplant that results in:
  • Antibodies Binds To Tissue-Specific Antigens: where Body sees as non-self.
  • Hemolytic Disease: Mom Rh (-) + Baby Rh (+).
• Type III Hypersensitivity is used to fight Autoimmume Disease(like raynauds) by getting tissue Destroyed because Antigens gets stuck, Ab-Ag deposit= Serum Sickness,
  • Immune type reaction that occurs after receiving Injection or Medication.
• Neutrophils : Try to Digest. Results in complex = Leakage.
• Arthus Reaction: person is reexposed to an antigen that they previously have been sensitized To Raynaud Phenomenon: decrease bloodFlow to extremities

Immune Responses

• Cryoglobulins are Proteins in Blood That Precipitate when Exposed to Cold.
• Type IV (Delayed) = T-Cells (No ANTIBODIES) = Reaction delayed : poison ivy, cheap jewelry, graft/tumor rejection and contact dermatitis are good examples.
• Neoplasm (Neoplasia:) is when cells look dysplastic with unusual sizes and unusual shapes.

In-Situ Vs Invasive Neoplasm

• In-Situ Neoplasm is related to skin cancer / Abnormalities that are contained and havent spread whereas Invasive Neoplasm are that which invades surrounding tissue.
• Preceded by cellular dysplasia which causes cells don’t look nirmal because they are abnormal and divided

Mitotic Index

• Cells have a high(er) Mitotic Index; and that’s the rate cells can divide through mitosis.
• Benign versus Malignant Tumour: the first on non-cancerous and doesn’t spread (Beter prognosis, and hogs nutrition/blood from the body) whilst Malignant does = Higher Mitotic index

Metastisis, Extravasation Vs Tumers

• Metastasis where the tumor is fragmenting and traveling to blood and Lymph. Extravasation is when this tumor has a chance To grow Branches To Spread.
• Capsule= layer of tissue that keeps Tumor contained (mostly Bening Tumors)
• Difference of cells through metabolic pathways.
• TUMOR-MANY TYPES
  • Carcinoma (Epithelial tissue derived)(most Tumors). Carcinoma (in situ): non-invasive (skin cancer Tumors).
  • Adenocarcinoma (Gland/Duct tissue)
• can effect the rest of Body with hormone concentrations
• Sarcoma (connective tissue derived) = BONE (OSTEOSARCOMA) Lymphoma = (Lymphatic system)
• Leukemia= (Bone marrow blood) Teratoma= ( Germ cell)( Teeth)

Clinical staging

• zero= no cancer
• Stage 2= Local/Invasive
• Stage 3(C)=To Regional area
• Stage 4D distance cite
• TNM (T= degree of cancer spread)

Tumor-markers

• Found on cell membrane-Cell Used for Screen Diagnosis of Tumor

Cancer Genetic Basis

"Multi-Hit Hypothesis": Older cells are more prone to replication because they replicate more

• Genetic factors: Mutations in DNA Clonal Proliferation = Competitively Advantage Inappropiate signalling
  Apoptosis pathways = “cell immortality” Cells secrete Angiogenic factors which make make more cells
• Internal Protection For Cancer: antiogengnes (suppressors) Metasis, no longet depend on another Fragments and goes thru other cells
• T Cells: can fight cell antigen