NURS 2020 Unit 4 Inflammation Immune Disorders Leukemias and Lymphomas PDF

NURS 2020 Advanced Pathophysiology and Microbiology Unit 4 Inflammation, Immune Disorders, Leukemias, and Lymphomas Avinash Thadani, PhD HBNA  Content...

NURS 2020 Advanced Pathophysiology and Microbiology Unit 4 Inflammation, Immune Disorders, Leukemias, and Lymphomas Avinash Thadani, PhD HBNA  Content Inflammation Hypersensitivity reactions Immune Disorders HIV/AIDS Leukemias: ALL, AML, CLL, CML, MM Lymphomas: Hodgkin vs. Non-Hodgkin Readings: Unit 4 Slide deck and the other learning resources posted on the Bb shell 2  Inflammation Inflammation is the body’s response to traumatic, chemical, or infectious insults The inflammatory cascade is a complex process that involves various parts of the immune system, including the innate, humoral, and cellular responses as well as the complement proteins and various cytokines There are numerous inflammatory mediators that are recruited to the site of injury including cytokines and prostaglandins The ultimate goal of inflammation is to promote tissue healing 3  Local Inflammation Inflammation restricted to a specific site of insult Five cardinal clinical manifestations of local inflammation: 1. Redness Most of the inflammatory mediators released promote vasodilation to increase the flow of blood to the area to deliver immune cells, phagocytes, nutrients, and oxygen 2. Heat Increased blood flow as well as increased metabolism 3. Swelling Most inflammatory mediators increase vascular permeability to allow for easier passage of the immune cells from blood to the tissue space 4  Local Inflammation Five cardinal clinical manifestations of local inflammation, cont’d: 4. Pain Swelling increases pressure on the free nerve ending; inflammatory mediators (e.g., prostaglandins) increase the sensitivity of the free nerve endings) 5. Loss of function Temporary loss of function of the affected area (especially in peripheral limbs) 5  Systemic Inflammation Inflammation that is more widespread; can affect an entire organ or the whole body Clinical manifestations depend on the organ(s) affected (e.g., inflammation of the liver or hepatitis will be discussed in the gastrointestinal disorders unit) Often occurs due to a systemic bacterial infection Lab tests for systemic inflammation: ESR (erythrocyte sedimentation rate) useful for serial tracking of systemic inflammation CRP (C-reactive protein) currently preferred test 6  Hypersensitivity Reactions Lytvyn, Y., Qazi, M. A., Li, M., Warmerdam, J. van, Erickson, A., Parker, J., Chang, T., Damian, A., Li, W. W., Singh, A., Baker, B., Huilin Lu, C., & Tan, C. C. (Eds.). (2022). Toronto notes 2022: Comprehensive medical reference and a review for the Medical Council of Canada Qualifying Exam (MCCQE) (38th edition.). Toronto Notes for Medical Students. 7  Hypersensitivity Reactions Lytvyn, Y., Qazi, M. A., Li, M., Warmerdam, J. van, Erickson, A., Parker, J., Chang, T., Damian, A., Li, W. W., Singh, A., Baker, B., Huilin Lu, C., & Tan, C. C. (Eds.). (2022). Toronto notes 2022: Comprehensive medical reference and a review for the Medical Council of Canada Qualifying Exam (MCCQE) (38th edition.). Toronto Notes for Medical Students. 8  Hypersensitivity Reactions Lytvyn, Y., Qazi, M. A., Li, M., Warmerdam, J. van, Erickson, A., Parker, J., Chang, T., Damian, A., Li, W. W., Singh, A., Baker, B., Huilin Lu, C., & Tan, C. C. (Eds.). (2022). Toronto notes 2022: Comprehensive medical reference and a review for the Medical Council of Canada Qualifying Exam (MCCQE) (38th edition.). Toronto Notes for Medical Students. 9  Anaphylaxis Definition: An exaggerated immune-mediated Type I hypersensitivity reaction that leads to systemic histamine release, increased vascular permeability, and vasodilation Etiology: Allergic (re-exposure to an allergen) Pathogenesis: Type I hypersensitivity reaction Most common triggers: foods (e.g., nuts, shellfish, MSG), insect stings, drugs (e.g., penicillin, NSAIDs, ACEI), radiographic contrast media, blood products 10  Anaphylaxis Clinical manifestations: Respiratory distress (e.g., dyspnea, wheeze, stridor, hypoxemia) Hypotension and hypoperfusion leading to end-organ dysfunction (e.g., hypotonia, syncope) Skin-mucosal involvement (e.g., swelling, rash) Persistent GI symptoms (e.g., crampy abdominal pain, vomiting) Anaphylaxis should be suspected if airway, breathing, or circulation compromise is present after exposure to a known allergen 11  HIV and AIDS Etiology: Infection with the HIV-1 retrovirus (less commonly HIV-2); host cell is the CD4 cell (Helper T cell) Risk factors: Unprotected sexual intercourse (especially anal sex), large number of sexual partners, previous or concurrent STI, sharing of IV drug paraphernalia Pathogenesis: As the virus replicates inside the CD4 cell, it eventually causes the destruction of these cell resulting in the drop in the CD4 count. The decline in the CD4 count is directly related to the rise in the severity of the clinical manifestations. 12  HIV and AIDS Clinical manifestations: i. Initial acute infection: Flu like illness (e.g., fever, pharyngitis, lymphadenopathy, rash, myalgias, headache, GI symptoms, oral ulcers, weight loss) 2-6 wk post exposure lasting ~ 2 wk ii. Asymptomatic phase (several years): viral replication (in lymph nodes) and CD4 destruction continues. This phase is generally benign. Eventually progresses to AIDS when CD4 count drops to a sufficient low level. Normal CD4 count in adults: 500-1100 cells/mm3; drops 60-100 cells/mm3 but is variable iii. AIDS: Recurrent, severe, and potentially life-threatening infections (e.g., pneumonia and fungal infections) and opportunistic malignancies (e.g., Kaposi sarcoma). This is an example of secondary immunodeficiency. By 10 yr post-infection, 50% have AIDS, 30% display milder symptoms, and 20% of total WBC differential consists of blasts, this is acute leukemia and is a medical emergency 17  Leukemia vs. Lymphoma Leukemia: Malignant cells arise in bone marrow (BM) that may spread elsewhere (including blood, lymph nodes, lymphoid tissue) Lymphoma: malignant cells arise in lymph nodes and lymphoid tissues that may spread elsewhere (including blood and BM) BUT the hematological malignancy is not solely defined based on where the the malignant cells are found; they are also classified based on the characteristics of the cell (histology, histochemistry, immunotyping, cytogenetics, molecular mutations, etc.) 18  Acute Leukemia Definition (WHO): presence of 20% blast cells or greater in the peripheral blood or BM at presentation Classification: divided into myeloid (acute myeloid leukemia, AML) and lymphoid (acute lymphocytic leukemia, ALL) depending on whether the blasts are myeloblasts or lymphoblasts respectively 19  Classification of Leukemias Lytvyn, Y., Qazi, M. A., Li, M., Warmerdam, J. van, Erickson, A., Parker, J., Chang, T., Damian, A., Li, W. W., Singh, A., Baker, B., Huilin Lu, C., & Tan, C. C. (Eds.). (2022). Toronto notes 2022: Comprehensive medical reference and a review for the Medical Council of Canada Qualifying Exam (MCCQE) (38th edition.). Toronto Notes for Medical Students. 20  Classification of Leukemias MPN: Myeloproliferative Neoplasms Lytvyn, Y., Qazi, M. A., Li, M., Warmerdam, J. van, Erickson, A., Parker, J., Chang, T., Damian, A., Li, W. W., Singh, A., Baker, B., Huilin Lu, C., & Tan, C. C. (Eds.). (2022). Toronto notes 2022: Comprehensive medical reference and a review for the Medical Council of Canada Qualifying Exam (MCCQE) (38th edition.). Toronto Notes for Medical Students. 21  Acute Myeloid Leukemia Definition: rapidly progressive malignancy characterized by failure of myeloid cells to differentiate beyond blast stage Epidemiology: incidence increases with age; median onset is 65 yr; 80% of acute adult leukemias; accounts for ~10% of childhood leukemias Risk factors: male, older age, smoking, obesity, radiation, Down syndrome Pathogenesis: uncontrolled growth of blasts in the marrow leads to: Suppression of normal hematopoietic cells Appearance of blasts in peripheral blood – risk of leukostasis Accumulation of blasts in other sites (e.g., skin, gums) Metabolic consequences (e.g., tumour lysis syndrome) Presence of Auer rods in peripheral blood smear is pathognomonic for AML 22  Acute Myeloid Leukemia Clinical manifestations: Due to BM failure: anemia, thrombocytopenia, neutropenia; leads to increased risk of infections and fever Skeletal pain and bony tenderness (due to accumulation of blasts in BM) Organ infiltration Gingival hypertrophy (dentist may notice first) Hepatosplenomegaly (also present in ALL) Lymphadenopathy (not marked in ALL) Leukostasis: large no. of blasts leads to defective circulation leading to hypoxia and hemorrhage; may causes respiratory distress, CNS bleeding, etc. Tumour lysis syndrome: hyperkalemia 23  Acute Myeloid Leukemia BM aspirate for definitive diagnosis (>20% blast count) Treatment: chemotherapy (rapidly fatal without treatment) Prognosis: Achievement of 1st remission: 70-80% if 60 yr old Median survival is 12 – 24 months 24  Chronic Myeloid Leukemia Definition: increased proliferation of granulocytic cell line without the loss of their capacity to differentiate Epidemiology: occurs in any age group (mostly middle age to elderly) with a median age of 65 yr Pathogenesis: Philadelphia (Ph) chromosome formed; translocation between chromosomes 9 and 22 The c-ABL proto-oncogene is translocated from chromosome 9 to the “breakpoint cluster region” (BCR) of chromosome 22 to produce the BCR- ABL fusion gene, which is a active tyrosine kinase 25  Chronic Myeloid Leukemia 3 clinical phases: Chronic phase: 85% diagnosed here Few blasts (20% blasts reflective of acute leukemia (AML) 26  Chronic Myeloid Leukemia Clinical manifestations: 20-50% are asymptomatic when diagnosed (incidental lab finding) Non-specific symptoms: fatigue, weight loss, malaise, diaphoresis, fever Secondary to splenomegaly: early satiety, LUQ fullness/pain, shoulder tip pain (referred) Anemia Bleeding (secondary to platelet dysfunction) Pruritis (secondary to increased histamine release) 27  Chronic Myeloid Leukemia Treatment: Imatinib inhibit the mutant tyrosine kinase protein produced by the BCR-ABL gene fusion product (Ph+) Prognosis: For those who respond to imatinib, >90% 6 yr overall survival rate For those who don’t respond fully to imatinib: 66% 6 yr overall survival rate May proceed to acute phase (blast crisis) (i.e., AML) 28  Primary vs. Secondary Polycythemia Polycythemia vera is a form of primary polycythemia Secondary polycythemia: Living at high altitudes (low partial pressure of oxygen) Other causes of chronic hypoxemia Smoking Surreptitious use of EPO (e.g., doping) 29  Polycythemia Vera Definition: stem cell disorder characterized by elevated RBC mass (erythrocytosis) with or without WBC or platelet production; Lab tests: Hb elevated, Hct elevated (>49% in men, >48% in women), serum EPO level below normal Clinical manifestations: Secondary to high RBC mass and hyperviscosity: headache, dyspnea, dizziness, tinnitus, HTN Increased risk of thrombosis Splenomegaly, hepatomegaly Facial plethora/ruddy complexion, palms also affected Pruritis, especially after warm bath/shower Treatment: phlebotomy to keep Hct F Clinical manifestations: Bone disease: bony tenderness, pathological fractures; lytic lesions are classical (e.g., in skull, proximal long bones, spine, ribs) due to increased bone resorption Pain (usually back) Anemia (due to BM suppression): fatigue, weakness, pallor 35  Multiple Myeloma Clinical manifestations, cont’d: Bleeding complications (secondary to thrombocytopenia) Weight loss Infections (due to lack of normal B cells) Hypercalcemia (due to increased bone resorption) Renal failure 36  Multiple Myeloma Clinical manifestations acronym: CRAB HyperCalcemia Renal failure Anemia Bony lytic lesions Lab finding: Bence-Jones protein (light chains of the monoclonal antibodies) found in urine Treatment: Autologous stem cell transplant if 70 yr or transplant ineligible Prognosis: median survival 3 – 7 yr 37  CLL vs Multiple Myeloma Lytvyn, Y., Qazi, M. A., Li, M., Warmerdam, J. van, Erickson, A., Parker, J., Chang, T., Damian, A., Li, W. W., Singh, A., Baker, B., Huilin Lu, C., & Tan, C. C. (Eds.). (2022). Toronto notes 2022: Comprehensive medical reference and a review for the Medical Council of Canada Qualifying Exam (MCCQE) (38th edition.). Toronto Notes for Medical Students. 38  Lymphomas Definition: Collection of lymphoid malignancies in which malignant lymphocytes accumulate at lymph nodes and lymphoid tissues Leads to lymphadenopathy, extranodal disease, and constitutional symptoms 39  Hodgkin Lymphoma Definition: malignant proliferation of lymphoid cells with Reed-Sternberg cells (believed to arise from germinal centre B cells) Epidemiology: bimodal distribution with peaks at 20 yr and >50 yr; association with EBV in up to 50% of cases (causal role?) Spread: Starts at a single lymphatic node and spreads to adjacent nodes (i.e., contiguous spread) 40  Hodgkin Lymphoma Clinical manifestations: Asymptomatic lymphadenopathy (70%) Non-tender, rubber consistency; cervical/superclavicular (60-80%), axillary (10-20%), inguinal (6-12%) Splenomegaly (50%) with or without hepatomegaly Mediastinal mass: found on CXR, may be symptomatic (cough) Constitutional symptoms: unintentional weight loss, fever and night sweats (without evidence of infection), extreme fatigue, pruritis 41  Non-Hodgkin Lymphoma (NHL) Definition: malignant proliferation of lymphoid cells of progenitor or mature B- (85%) or T- or NK- (15%) cells WHO classification (of B-cell NHL): Indolent (35-40%) e.g., small lymphocytic lymphoma Aggressive (~50%) e.g., diffuse large B-cell lymphoma Highly aggressive (~5%) e.g., Burkitt’s lymphoma 42  Non-Hodgkin Lymphoma (NHL) Clinical manifestations: Painless lymphadenopathy, usually in more than one lymph node region (i.e., non-contiguous spread) Widespread lymphadenopathy Constitutional symptoms not as common as in Hodgkin lymphoma Pancytopenia (when BM is involved): anemia, neutropenia, thrombocytopenia Hepatosplenomegaly Extranodal involvement: GI tract, testes, bone, kidney 43  Summary Please learn the pathophysiology (etiology, modifiable risk factors, pathogenesis (briefly), and most importantly the clinical manifestations) of the various diseases/disorders/conditions covered in this slide show and listed in the learning outcomes of Unit 4 in the syllabus You will only be assessed on the diseases/disorders/conditions that are listed in the leaning outcomes for Unit 4 Please contact me via email ([email protected]) if you require any clarification/assistance 44  Next Lesson Unit 5 Gastrointestinal Disorders 45