PATHO 370 - Pathophysiology Study Guide Complete 2023

PATHO 370 - Pathophysiology Study Guide Complete 2023. Intro to Pathophysiology Pathophysiology ● Pathophysiology - Deranged function in an individual or an organ due to a disease Etiology Classifications ○ Idiopathic - Cause is unknown ○ Iatrogenic - Cause results from unintended or unwanted medical treatment ● Risk Factor: The chances of you getting something ○ A factor that when present increases the likelihood of disease Stages and Clinical Course ● Latent Period ○ From Exposure of tissue to the injurious agent and first appearance of signs and/or symptoms ● Prodromal period ○ First signs and/or symptoms appear indicating the onset of disease ● Acute phase ○ Disease/illness reaches its full intensity Stages and Clinical Course ● Exacerbation ○ A sudden increase in severity of disease or signs or symptoms ● Remission ○ Decrease in severity, signs, or symptoms; may indicate the disease is cured ● Convalescence ○ Stage of recovery after a disease, injury, or surgical procedure ● Sequela ○ Subsequent pathologic condition resulting from an illness ■ Ex. You fall take blunt force trauma to the head end up with brain fog ■ Sequela of having brain damage = brain fog Levels of Prevention ● Primary ○ Altering susceptibility or reducing exposure for susceptible persons ○ Avoidance and Vaccination ● Secondary ○ Early detection, screening, and management of disease ○ Annual physicals, mole checks, mammograms ● Tertiary ○ Rehabilitation, supportive care, reducing disability, and restoring effective functioning ○ You’ve already had it, treating you trying to reduce the effects Chapter 2: Homeostasis, Allostasis, and Adaptive Responses to Stressors Homeostasis is stability ● A state in which all systems are in balance; Equilibrium ● An ideal “set point” despite alterations within the body Allostasis ● Ability to adapt to changes and maintain an internal environment to support these changes, for the purpose of survival and well being Stress ● Physical, chemical, or emotional factor resulting in the tension of body or mind ● Not all Stress is harmful General Adaptation Syndrome (GAS) (Selye) ● 3 stages ○ Alarm - fight or flight as a response to stressful stimulus; Homeostasis is thrown off ○ Resistance/ Adaptation - In the resistance alarm stage was survived and we went back to homeo. Adaptation we have now learned to cope with a new balance; Resist having alarm response OR adapt ■ Lifting weights causing an increase in muscle this is adaptation/resistance ○ Exhaustion - No longer able to return to homeo or allostasis. Wear and Tear; Disease sets in ■ Physical degradation of your body, emotional toll that high stress takes ● Allostatic overload: inadequate adaptation mechanisms or excessive allostatic load; results in inability to maintain homeostasis Neurohormonal Mediators of Stress and Adaptation - Secreted by Adrenal Glands Catecholamines ● Sympathetico-adrenal system response mediates the fight-or-flight response ● Examples ○ Norepinephrine and epinephrine Norepinephrine ● Constricts blood vessels and raises blood pressure ● Increases heart rate ● Reduces gastric secretions ● Increases night and far vision Epinephrine ● Increases the release of glucose from the liver (glycogenolysis) and elevates blood glucose levels ● Increase heart rate ● Bronchodilation ● Increase blood sugar ● Increase blood pressure Adrenocortical Steroids ● May synergize or antagonize effects of catecholamines ● Examples ○ Cortisol and aldosterone Cortisol ● Primary glucocorticoid ● Affects protein metabolism, converts it to glucose, under high stress converts glucose to fat ● Increases blood sugar ● Promotes appetite and food-seeking behaviors ● Has anti-inflammatory effects Aldosterone ● Primary mineralocorticoid ● Promotes reabsorption of sodium and water ● Increases blood pressure Endorphins and Enkephalins ● Endogenous opioids (body’s natural pain relievers) ○ Raise pain threshold Immune Cytokines - Adrenal Gland ● Secreted by macrophages during stress response ○ Enhance immune system response ● Example ○ Interleukin-1 → From Macrophages: Tells macrophages to be alert Chapter 4 Cell Injury, Aging, and Death Reversible Cell Injury: Can be changed back to healthy cells 1. Hydropic Cell Injury ○ Sodium Potassium pump malfunctions (lack of ATP). ○ Excess Sodium inside the cell leads to excess water inside the cell. ■ Where Sodium Goes Water Follows ■ Where Sodium Goes Potassium Leaves ○ The cell swells. 2. Intracellular lipid accumulation. ○ Ex: Fatty Liver Disease. ■ Caused by Alcohol ● Liver is too busy breaking down alcohol that it can't break down fat from food so it stores the fat in the liver for later. But then later you eat more food so it breaks down the new fat and the old fat stays sitting in the liver ● Old fat forms scar tissue around the liver ■ Also caused by High fructose corn syrup in sodas 3. Accumulation of Exogenous (from the outside) or Endogenesis (made inside the cell) particles indicate poor cellular metabolism. ○ Improperly folded proteins are another product that can accumulate inside cells. ○ They are handled by Chaperone proteins to refold protein. ○ If Chaperone fails then another protein called Ubiquitin breaks apart the protein. ■ UBiquitin - Break down proteins Adaptation - If Cells are put under a demand they will adapt to try to handle that demand ● Atrophy ○ Decreased size. (disuse, starvation, ischemia, and denervation) ■ Things are wasting away ● Hypertrophy ○ Increase in size to increase demand (work). Increase in protein content. ● Hyperplasia ○ Increase in number of cells. Same Size ■ Most benign tumors are hyperplasia ● Metaplasia ○ Change from one type of cell to another. ■ Ex- Cigarette smoke causes glandular epithelium to be replaced with squamous epithelium. (bronchial epithelium) → Its Normally Columnar Shaped ● Dysplasia ○ Disorganized cells –greater risk of becoming cancerous. Irreversible Cell Injury ● Necrosis –Death Types of necrosis ● Coagulative necrosis ○ Ischemia kills cells but the proteins inside the cells survive and clump together and become solid. → Ischemia: Couldn’t get blood supply there is no oxygen ● Liquefactive necrosis ○ Cells die quickly and release enzymes which denature cells. → More common in Brain like stroke ● Caseous necrosis ○ In lungs from TB looks like cottage cheese. ● Gangrene necrosis ○ Large area suffers ischemia. Cells die with no immune response leads to infection and death. Apoptosis ● Programmed death of a cell. Cell Injury ● Etiology – lack of oxygen Ischemia or Hypoxia. ● Nutritional –Vitamins and minerals: Needed for cells to survive ● Infection ● Chemicals –Poisons Aging ● Cells replicate throughout our life. ● With each chromosomal replication Telomeres get shorter. ● Telomeres are like the hourglass timer. When they get to short cells no longer go through mitosis and die. Chapter 7 Neoplasia Neoplasia: ● Means “new growth” ● Implies abnormality of cellular growth/tumor ● Malignant neoplasm is cancer. ● Benign growth is generally easily cured. ● Cancer is associated with altered expression of cellular genes. Benign vs. Malignant Growth ● Malignant Tumor ○ Can kill host if untreated ○ Confirmed by invasive or metastasizing nature → It moves ○ It’s Lacking Tissue-specific differentiation (does not closely resemble tissue type of origin) ■ Greater degree of anaplasia indicates aggressive malignancy. ● Anaplasia: It didn’t grow up, it didn’t differentiate ○ Grows rapidly and metastasizes ○ May initiate tumor vessel growth ○ Frequently necrotic ○ Dysfunctional ● Benign Tumor: ○ Does not have potential to kill host, but may be life-threatening because of its location ○ Many are encapsulated The Malignant Phenotype (Cont.) ● Antisocial behaviors include: ○ Genetically unstable and evolve by accumulating new mutations at a much faster rate than normal cells ■ Always changing and mutating Two types of carcinogens (Cancer causing chemical) ○ Initiator (causes genetic damage) ■ Initiates the problem ○ Promoter (promotes tumor growth) ■ Keeps the problem going Genetic Mechanisms of Cancer: ● Carcinogen ○ Potential cancer-causing agent ○ Initiator and Promoter ● Proto-oncogene ○ Enhance growth-producing pathways ○ Induces growth ● Oncogene ○ Proto-oncogene in its mutant overactive form ○ Does all the replicating ○ The proto-oncogene that got mutated that is causing the cancer to keep growing ● Tumor suppressor gene: Suppress expression of that gene ○ Inhibits cell proliferation ○ Cancers may arise when tumor suppressor gene function is lost or abnormally inhibited. ○ Regulates stuff; makes sure that things are going right From Proto-Oncogene to Oncogene: ● Proto-oncogenes → Makes oncogenes show ○ Become activated oncogenes when mutations alter their activity so that proliferation-promoting signals are generated inappropriately ○ Oncogenes introduced to host cell by retrovirus ○ Proto-oncogene within a cell suffers a mutagenic event. ○ DNA sequence may be lost/damaged and allows proto-oncogene to become abnormally active. ○ Error in chromosome replication causes extra copies of proto-oncogene in the genome. ● Retrovirus ○ HIV ■ Kaposi’s sarcoma ○ Epstein–Barr virus ■ Burkitt lymphoma ○ Human T-lymphocyte virus type 1 ■ Adult T-cell leukemia/lymphoma Chapter 10 - Alterations in Immune Function Immune System ● Defends body against invasion or infection by antigens ● Patrols for and destroys abnormal or damaged cells. What is an Antigen? ● An Identifying protein on outside of cell ● Like a tattoo for a gang member ● Body must be able to recognize tattoos from people that are not part of own gang Autoimmunity Possible Theories ● Antigenic mimicry theory ○ Self/foreign antigens made of same materials, so small alterations in self tissue lead to attack ■ Where healthy and foregin antigens are confused ● Release of sequestered antigens theory ○ Self antigens hidden (sequestered) with lymphocytes during fetal development ○ Women get the RhoGAM shot to protect their second child ○ The shot contains antibodies (collected from plasma donors) that stop your immune system from reacting to your baby's Rh positive blood cells. ● T-cell theories: T- Cells: Control immune response; produced in bone marrow, then go to thymus gland ○ Thymus gland defects ○ Decreased suppressor T-cell function ○ Altered T helper cell function ● B-cell theories: The T-cells tell the B cells to stop or go ○ B cells lose their responsiveness to suppressor T-cell signals. ○ Overactivation of B cells ● Mast cell theory : Mast cells are for allergies ○ Cytokines are released causing activation of other cells. Autoimmunity Treatment ● Individualized immunosuppressive therapy ○ Corticosteroids (Bring down inflammatory response) and cytotoxins (Kill WBC’s) ○ Tumor necrosis factor inhibitors and immunomodulators: Try to bring down immune response ○ Therapeutic plasmapheresis: For severe cases ■ Take Blood out → Filter plasma→ Take out antigens → Then put blood back in All these treatments are meant to bring down your bodies immune response so your body doesn’t attack itself Hypersensitivity: An overreaction → Going to be an allergy ● Hypersensitivity types I, II, and III ○ Mediated by antibodies produced by B lymphocytes (B cells) ● Hypersensitivity type IV ○ Mediated by T cells ■ The only one that involves t cells Type I Hypersensitivity ● Pathogenesis ○ IgE is the principle mediating antibody. ○ Think Allergies ○ Epipen → Epinephrine: Is a bronchodilator, opens airways to breathe Type II Hypersensitivity ● Also known as tissue-specific, cytotoxic, or cytolytic hypersensitivity ● Think tissue rejection Donor Type III Hypersensitivity: More than one body system ● Body's own antibodies attach to antigen. (Normal). This complex is not cleared up by Phagocytes (not normal), instead they embed in body tissue. This causes chronic inflammation of the tissue. Ex: Systemic Lupus Erythema. ○ Connective tissue disorders affected Type IV Hypersensitivity ● T-Cell mediated response. Helper T- Cell falsely recognizes antigen as foreign mounts response. ● No B-Cell involvement What is a Plasma Cell? ● An activated B-Cell differentiated to fight infections → It produces immunoglobulins Chapter 11 Malignant Disorders of White Blood Cells (Leukemias) Malignant Disorders of White Blood Cells ● Leukemia, lymphoma, and plasma cell myeloma (multiple myeloma)—common neoplastic disorders of the bone marrow and lymphoid tissues ● Leukemias—circulating tumors that primarily involve blood and bone marrow ○ Affects the Leukocytes a.k.a. White Blood Cells ○ White Blood Cells are: Granulocytes (Neutrophil, eosinophil, and basophil), B (lymphocyte) Cells, T (lymphocyte) Cells, Natural Killer Cells, and macrophages ● Lymphoma—tends to localize in lymph tissues; is often disseminated to other sites at diagnosis ○ Affects the T-Cells and B Cells ● Plasma cell myeloma (Multiple Myeloma)—malignant transformation of B-cell plasma cells; likes to form localized tumors in bony structures ○ Multiple myeloma holes in the bone caused by plasma cells What is a Neoplasm? ● a new and abnormal growth of tissue in some part of the body Hematology ● During Hematopoiesis a bone marrow stem cell differentiates into a Myeloid stem cell or a Lymphoid Stem Cell. ● Myeloid Stem Cells – become either a RBC, Platelet, or a White Blood Cell ● Lymphoid Stem Cells – become either a T lymphocyte or a B lymphocyte. ● Leukemia produces an Abnormal WBC or Lymphocyte. ○ Crowds out other blood cells. ● Possible causes ○ Viruses ○ Radiation exposure ○ Chemical exposure (slight) ○ Reduction or alteration in normal hematopoiesis (is making blood cells) ○ Some genetic diseases Diagnosis of Hematologic Neoplasms: Signs and Symptoms of Blood Disorders/Cancers ● Most Common Clinical Manifestations ○ Leukopenia – decrease in leukocytes ■ Lymphadenopathy: Problem in lymph nodes ■ Joint swelling and pain: Because cancer is growing in bone marrow it puts pressure in bone marrow ■ Weight loss ■ Anorexia ■ Hepatomegaly: Enlarged Liver ■ Splenomegaly: Enlarged Spleen because there's a lot of lymphoid tissue in spleen ○ Anemia – decrease in RBC (Not enough Oxygen) ■ Pallor: Color of skin light + Washed Out ■ Fatigue ■ Malaise: Feeling sick ■ Shortness of breath ■ Decreased activity tolerance ○ Thrombocytopenia: Issue in forming blood clots so you bleed a lot ■ Penia = not enough ■ Low Platelet count ■ Petechiae: pinpoint, round spots that appear on the skin as a result of bleeding ■ Easy bruising ■ Bleeding gums ■ Occult hematuria: Blood in Urine only visible through microscope ■ Retinal hemorrhages: disorder of the eye in which bleeding occurs in the retina Myeloid Neoplasms → Myeloid = not in lymph nodes ● A rapid increase in stem cells or transformation of them occurs in the bone marrow; stem cells are now abnormal Lymphoid Neoplasms ● Include malignant transformations of B, T, and Natural killer cells ● Leukemia—when present in blood/marrow ● Lymphoma—when localized in lymphoid tissues ○ T cells or B Cells usually Plasma Cell Myeloma - (Multiple Myeloma) ● Pathogenesis and Clinical Manifestations ○ Also known as multiple myeloma ○ Malignant disorder of mature, antibody-secreting B lymphocytes (plasma cells) ○ Occurs exclusively in adults ○ 50% - will have Renal (Kidney) Insufficiency. ○ Holes in Bone X Ray Hodgkin Disease ● If Reed-Sternberg Cells are Present: It’s Hodgkins ○ If they are not present its non-Hodgkin’s Chapter 13 Alterations in Oxygen Transport Function of Blood ● Maintain body ph 7.35 – 7.45 ○ Kidney and Lung maintain Blood pH ● Prevents blood loss (platelets) ● Moves Oxygen to cells takes Carbon Dioxide from cells (Red Blood Cells). ● Fight Infections (White Blood Cells) ● Plasma Proteins from Liver –Albumin, Globulins, Fibrinogen. ● Not enough albumin = liver damage Red Blood Cells (Erythrocytes) ● Most abundant blood cell ● Transport oxygen to tissues ● Remove carbon dioxide from the tissues ○ Because Co2 buildup leads to acidity in blood ● No Nucleus: Because they’re disposable ● 120 day lifespan. When destroyed Iron is Recycled into new RBC’s. Porphyrin gets converted to Bilirubin. Bilirubin goes to the liver and becomes Bile. ○ Bile: Used to emulsify fat so we get fat from diet into system ○ Bile made in liver stored in gallbladder ● Oxygen attaches to Hemoglobin (appx: 270 million in one RBC) at lungs. (oxyhemoglobin – bright red) Arteries ● Levels of oxygen in blood controls production of red blood cells. Hemoglobin Synthesis 1. Low level of oxygen concentration in blood. 2. Kidneys release Erythropoietin (hormone) into the bloodstream. a. So if you have renal disease you can become anemic 3. Erythropoietin stimulates bone marrow to produce more Red Blood Cells. 4. When blood oxygen levels have increased enough then Erythropoietin stops and RBC manufacturing slows. Structure and Function of Red Blood Cells ● Nutritional Requirements for Erythropoiesis ○ Requires adequate amounts of iron, protein, vitamins, and minerals ■ Folate and B12 deficiencies lead to impaired DNA synthesis in erythroid cells because the vitamins are coenzymes of key reactions in cellular metabolism. ● Absorption of B12 requires intrinsic factors. ○ Pernicious Anemia = Lack of intrinsic factor Gas Transport and Acid-Base Balance ● Carbon Dioxide Transport ○ RBCs contain the enzyme carbonic anhydrase. ■ Greatly increases conversion of CO2 and water into HCO3− and H+ at the tissue level. More H+ equals more Acidic. ■ In the lungs, the reaction proceeds in reverse, producing CO2 and water, removing H+. Lowers Acidity. ○ 7.35-7.45 the pH that our blood wants to be at ○ We breathe because we need to get rid of Co2. When we hold our breath the blood gets acidic. When you hyperventilate your blowing out too much Co2, you faint, then cellular respiration kicks in and your Co2 levels go back up Anemia ● Anemia is a deficit of red cells. ○ Low oxygen-carrying capacity leads to hypoxia. ● Opposite of anemia: polycythemia ○ Excess of red cells ○ Increases blood viscosity and volume Anemia Related to Decreased Red Cell Production