Pathology & Physiology Overview PDF

Etiology: origin or cause of disease Pathogenesis: steps leading to disease Morphology: structural alterations in cells and tissues of body Targets of cell injury: mitochondria, calcium homeostasis disturbances, damage to cellular membranes, damage to DNA Physiological adaptation: response to normal...

Etiology: origin or cause of disease Pathogenesis: steps leading to disease Morphology: structural alterations in cells and tissues of body Targets of cell injury: mitochondria, calcium homeostasis disturbances, damage to cellular membranes, damage to DNA Physiological adaptation: response to normal stimulation by hormone or endogenous chemical mediators Pathologic adaption: response to stress that allow cell to escape injury Hypertrophy: increase in cell size causing increase organ size: LV hypertrophy Atrophy: decrease in size and function of cells: bedridden Hyperplasia: increase in number of cells resulting from an increased rate of cellular division: BPH Metaplasia: reversible change whereby adult cell type is replaced by another: barretts esophagus Necrosis: unregulated, inflammation, energy not required, cytolysis: membranes disrupted Apoptosis: programmed, tightly regulated, condensation- membranes intact, no inflammation, energy required, discrete DNA fragmentation Reactive oxygen intermediates: hydroxyl radical OH- is most damaging Role of NOS: vasodilation, antagonized platelet activation, decreases leukocyte recruitment Oxidative stress/excess free radicals cause: increased production of ROS, ineffective scavenging systems Antioxidants: breakdown-catabolize free rads, block formation of free rads, scavenge free rads, repair damage Propofol: antioxidant properties Desflurane: free oxygen rad released more by des than sevo Sevo: does not induce generation of free rads Isoflurane: pro apoptotic effects; induce generation of amyloid beta protein (alzheimer disease) Acute: fast onset, neutrophil infiltration, mild tissue injury, prominent local and system signs Chronic: slow, monocytes/macrophages/lymphocytes, severe/progressive injury, fewer local/sys signs Leukocyte recruitment: margination/rolling- selectins, adhesion-integrins, transmigration- PECAM and collagenase, chemotaxis- chemokines and cytokines then call the WBC over to site of inflammation Histamine: vasodilation, increase vasc permeability, endothelial activation Serotonin: vasoconstriction and increased vasc permeability Arachidonic acid: 2 pathways: cyclooxygenase pathway COX 1 and 2: inhibited by ASA, NSAIDS, CoX2 inhibitors and steroids, lipoxygenase pathway: inhibited by steroids only Platelet activating factor: inflammatory mediator Cytokines: stimulate growth, differentiation, and function of leukocytes and immune cells, involved in systemic inflammatory response, hypotension-shock and cytokine storm Vasodilation: histamine, prostaglandins, prostacyclin, lipoxins, platelet activating factor Vasoconstriction: serotonin, thromboxane, leukotrienes Free radicals produced from: neutrophils, macrophages, endothelial cells Reversible cell growth: metaplasia and dysplasia Metaplasia: normal cells of one type are replaced by normal cells of another type that are better able to withstand stress Dysplasia: abnormality in maturation of cells within a tissue or irregularly shaped and disorganized cells Irreversible: benign and malignant benign : well-differentiated, normal to hyper, localized and typically encapsulated, press against another structure Malignant: dont respond to normal controls, loss of cell-to-cell adhesion and invasive Insertional mutagenesis: viral genes are incorporated into hosts genome at specific sites and cause cell transformation Doxorubicin: cardiotoxic and may need preop Echo or EKG Bleomycin: pulmonary effects and exacerbated by high O2 so deliver lowest possible FiO2 that is adequate Cisplatin: neurological/nephrotoxic Best approach of neuropathic pain is not opioids but toradol or acupuncture P53 is most common tumor suppressor gene that becomes mutated Function of p53 gene: cell quiescence, cell senescence, cell arrest, stimulate DNA repair pathway, trigger apoptosis Ras protein mutation can not deactivate signal for growth/division voluven/hetastarch is not recommended for HIPEC because it can cause clotting issues 70 =ultra obese CAD and DMII are independent risk factors for obesity Obesity respiratory effects: decreased FRC, ERV, TV and RV remains the same and increased O2 consumption Normal FRC is 35ml/kg and decreased with obesity Normal O2 consumption is 3.5ml/kg/min and increased with obesity Pcikwickian syndrome can develop hypersomnolence and: polycythemia, pulm HTN, RS HF- cor pulmonale Increased neck circumference: single largest predictor of difficult intubation Water soluble drug use lean body weight or adjusted body weight Fat soluble drugs use total body weight Lead body weight drugs: propofol induction, roc/vec, fent/sufent maintenance, remifentanil Total body weight drugs: prop maintenance, suc, cis/atracurium, fent/sufen loading Regional anesthesia is preferred anesthetic in obesity Erythropoiesis: regulates RBC production via feedback system that senses decreased oxygen delivery to kidneys and decreased hgb and increased RBC production Compensatory anemia mech: increase erythropoietin, increased hematopoiesis, blood redistribution from skin/renal to heart/brain, increased HR and CO, fatigue, weakness, dyspnea, tissue hypoxia- with 40% blood volume loss Morphological classifications: based on red cell size and shape MCV normal =90fl microcytic = decreased MCV: iron deficiency and thalassemia macrocytic=increased MCV: pernicious anemia Pernicious anemia: block binding of vitamin b12 to intrinsic factor normocytic = normal MCV: hemolytic anemia, G6PD def, sickle cell anemia, Hemolytic anemia hallmark sign: erythroid hyperplasia and reticulocytosis G^PD def: avoid meds that further depress G6PD which are: iso, sevo, reglan, penicillin, methylene blue Avoid meds that induce methemoglobinemia in G6PD pts: lidocaine, prilocaine, silver nitrate Events that initiate sickle cell anemia to avoid: decreased PaO2, decreased pH, dehydration, cold/stress/exertion/infection Sickle cell disease at increased complications with tourniquets and increase crisis Hemophilia A is factor VIII deficiency Hemo A: prolonged PTT (intrinsic pathway) and normal PT for labs To normalize factor VIII in hemo A: DDAVP 30-90 min prior to surgery Hemophilia B: factor IX deficiency and petechiae is more common Hemo B labs: prolonged PTT and normal PT Prophylaxis for hemo B: recombinant factor IX, Caution with factor IX prothrombin complex concentration for hemo B cause of risk of thromboembolic events Minor surgery: need platelet count 20-30 Major surgery: need 50 for adequate platelet neurosurgical/eye/neuraxial procedures need platelet count 100 or greater Heparin induced thrombocytopenia has type 1-nonimmune and Type 2-immune Type 2 HIT diagnosis: thrombocytopenia, timing of platelet reduction, presence of thrombosis, presence of other causes of thrombocytopenia Avoid prophylactic platelet transfusions with Type 2 HIT because of increased risk of thrombosis Neoplastic: lymphoid neoplasms and myeloid neoplasms Lymphomas and leukemias: uncontrolled proliferation and accumulation of single progenitor cell and decreased proliferation, production, and function of normal hematopoietic cells within bone marrow, gradual stem cell suppression Acute lymphomas or leukemias: undifferentiated or immature cells: cells non functional and onset of disease is abrupt and rapid with poor prognosis Chronic lymphomas and leukemias: cells differentiated, more mature and somewhat functional but do not function normally and slow onset with long duration Hodgkin lymphoma: from EBV infection or immunosuppressed state from germinal center B cells and initial lymph node involvement is above diaphragm and lymph node biopsy is diagnosis and has presence of reed sternberg giant cells Non-hodgkin lymphoma: spread throughout body including bone marrow and involves multiple peripheral nodes, noncontiguous spread and involves mesenteric and waldyer ring Sentinel node: first lymph node to which cancer cells are likely to spread from primary tumor Multiple myeloma: poorly controlled plasma B cells produce M protein and have defective light chain excreted as bence jones proteins that are toxic to renal tubular structures Acute lymphoblastic leukemia: most common cancer in kids, and has pre-B or pre-T cell neoplasms and is aggressive Chronic lymphocytic leukemia/small lymphocytic lymphoma: genetic mutation, neoplasm of mature B cells and most common leukemia in adults with slow progression Acute myelogenous leukemia: accumulation of blasts in marrow that can cause dyspnea on exertion, fatigue, bleeding gums, epistaxis, pallor, headache Chronic myelogenous leukemia: philadelphia chromosome and has BRC-ABL gene that does not inhibit differentiation Intrinsic pathway: activated by factor XII hageman factor by exposure to subendothelial tissue and measured by PTT Extrinsic pathway: factor II tissue factor through injury, PT assay