Questions and Answers
What is the primary host cell infected by the HIV-1 retrovirus?
Which of the following symptoms is commonly associated with the initial acute HIV infection?
What is the normal CD4 count range in adults?
Which diagnostic test is specifically used to measure the level of a marker for inflammation?
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What does the Erythrocyte Sedimentation Rate (ESR) test assess?
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The presence of which antibodies does the ANA test detect?
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What type of immune responses are involved in the inflammatory cascade?
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What is one characteristic of local inflammation?
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Which of the following is NOT a cardinal clinical manifestation of local inflammation?
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What is the primary mechanism behind the redness observed in inflammation?
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Which factor is likely to delay the healing process?
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What type of hypersensitivity response involves IgE and is commonly associated with allergic reactions?
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In which type of healing are wound edges brought together directly?
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Which of the following is classified as a secondary immunodeficiency?
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Which autoimmune disease results in the immune system attacking the thyroid gland?
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What distinguishes Type 4 hypersensitivity from the other types?
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Which condition is associated with a higher risk of developing multiple sclerosis?
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What is the primary impact of malnutrition on the immune response?
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What role do inflammatory mediators play in the swelling of tissues during inflammation?
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Which of the following factors does NOT impair the immune response?
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What is the primary characteristic of polycythemia vera?
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Which symptom is most commonly associated with polycythemia vera?
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What is the recommended treatment approach for managing polycythemia vera?
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Which laboratory finding is typically low in patients with polycythemia vera?
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What is a common complication associated with polycythemia vera?
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What primarily characterizes Acute Lymphoblastic Leukemia (ALL)?
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Which factor is NOT a risk for Acute Myeloid Leukemia (AML)?
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What is a common consequence of bone marrow failure in AML?
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Which symptom is least likely to be an early presenting symptom of ALL?
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What is the significance of Auer rods in a peripheral blood smear?
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Which of these statements accurately reflects the natural history of ALL?
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Which of the following is a common complication of elevated blast levels in AML?
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Which of the following clinical manifestations is common in both ALL and AML?
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What is a definitive diagnostic procedure for confirming tumour lysis syndrome?
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Which chromosome translocation results in the formation of the Philadelphia chromosome associated with Chronic Myeloid Leukemia?
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What is a common symptom associated with Plasma Cell Myeloma?
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Which of the following is part of the clinical manifestations acronym CRAB associated with Multiple Myeloma?
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What is the main characteristic of Hodgkin Disease?
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Which type of lymphoma is associated with a bimodal age distribution?
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Which of the following symptoms is a characteristic of Non-Hodgkin Lymphoma?
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What is a common treatment for Chronic Myeloid Leukemia that targets the mutant tyrosine kinase?
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What physiological change is most associated with plasma cell proliferation in Multiple Myeloma?
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What event is closely monitored for patients with a risk of progressing to Acute Myeloid Leukemia from Chronic Myeloid Leukemia?
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Study Notes
Inflammatory Response
- Inflammation occurs in response to traumatic, chemical, or infectious insults.
- The inflammatory cascade involves innate, humoral, and cellular immune responses, complemented by cytokines and proteins.
- Cytokines and prostaglandins are key inflammatory mediators recruited to injury sites.
- inflammation aims to promote tissue healing.
Diagnostic Tests for Inflammatory and Immune Responses
- CBC (Complete Blood Count): Assesses general blood health; identifies infections and immune responses.
- CRP (C-Reactive Protein): Measures inflammation; used to diagnose and monitor inflammation levels.
- ESR (Erythrocyte Sedimentation Rate): Assesses red blood cell settling; helps diagnose inflammatory diseases.
- ANA (Antinuclear Antibody): Detects autoimmune antibodies; used for diagnosing autoimmune conditions like lupus.
- Immunoglobulin Levels: Measures antibody levels; evaluates immune function and deficiencies.
Local and Systemic Manifestations of Inflammation
Local Inflammation
- Restricted to a specific insult site with five cardinal manifestations:
- Redness: Vasodilation increases blood flow to the affected area.
- Heat: Result of increased blood flow and metabolism.
- Swelling: Enhanced vascular permeability allows immune cell passage.
- Pain: Swelling exerts pressure on nerves; mediators heighten sensitivity.
- Loss of Function: Temporary impairment occurs, especially in limbs.
Systemic Inflammation
- Widespread effect, potentially impacting entire organs or the body.
- Clinical manifestations vary based on affected organs (e.g., hepatitis in the liver).
- Systemic infections often cause widespread inflammation.
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Lab tests:
- ESR for tracking systemic inflammation.
- CRP as a preferred testing method.
Healing Process
- First Intention: Wound edges are approximated directly leading to minimal inflammation and scarring (e.g., surgical incisions).
- Second Intention: Wound is left open to heal naturally, resulting in more inflammation and granulation tissue (e.g., large wounds).
Factors That Delay Healing
- Infection: Heightens inflammation, delaying healing.
- Poor Circulation: Reduces oxygen and nutrient delivery.
- Diabetes: Impairs tissue repair mechanisms.
- Malnutrition: Insufficient nutrients hinder recovery.
- Smoking: Diminishes blood flow.
- Chronic Diseases: Adversely affects healing capacity.
- Medications: Some treatments can impede healing.
- Age: Slower healing process associated with older age.
- Mechanical Stress: Disrupts repair processes.
- Underlying Conditions: Can negatively influence healing efforts.
Types of Hypersensitivity Responses
- Type 1 (IgE Mediated): Reacts to freely moving antigens; involves histamine release causing allergic reactions (examples: allergic asthma, anaphylaxis).
- Type 2 (Cytotoxic): Involves antibodies reacting to fixed antigens causing cell destruction (examples: transfusion reactions).
- Type 3 (Immune Complex): Formed by immune complexes causing inflammation (examples: post-streptococcal glomerulonephritis).
- Type 4 (Delayed): Mediated by T-helper cells and cytokine release causing a delayed immune response (examples: contact dermatitis, type 1 diabetes).
- Sensitization is required for Type 1 and Type 4 responses.
Factors Impairing Immune Response
- Chronic Diseases: Immunity reduced by conditions like diabetes and cancer.
- Malnutrition: Essential nutrients are vital for immunity; deficiencies harm response.
- Stress: Chronic stress suppresses immune function.
- Medications: Immunosuppressants diminish immune capacity.
- Aging: Older individuals typically face weaker immune responses.
- Infections: Some directly compromise immune functionality.
- Lifestyle Factors: Poor sleep, excessive alcohol, and smoking weaken the immune system.
Autoimmune Conditions
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SLE (Systemic Lupus Erythematosus): Autoimmune disease affecting multiple organs; symptoms include fatigue, joint pain, and a butterfly-shaped facial rash; influenced by genetics and environment.
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MS (Multiple Sclerosis): Autoimmune attack on myelin in brain and spinal cord; symptoms include movement and vision issues; linked to Epstein-Barr Virus (EBV).
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Hashimoto's Thyroiditis: An autoimmune disorder causing hypothyroidism; presents with fatigue and weight gain; treatment involves hormone replacement.
Immunodeficiencies
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Primary Immunodeficiencies: Genetic or congenital conditions present at birth, caused by genetic mutations (examples: SCID, CVID, XLA).
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Secondary Immunodeficiencies: Acquired conditions caused by infections or therapies (examples: HIV/AIDS, steroid therapy).
HIV and AIDS
- Etiology: Caused by HIV-1 (or HIV-2); primarily infects CD4 T-helper cells.
- Risk Factors: Unprotected sex, multiple partners, STIs, sharing IV drug equipment.
- Pathogenesis: HIV reduces CD4 count, correlating with clinical manifestations.
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Clinical Manifestations:
- Acute Infection: Flu-like symptoms appear 2-6 weeks post-exposure.
- Asymptomatic Phase: Lasts years; ongoing viral replication leads to gradual CD4 decline.
- AIDS: Characterized by severe infections and malignancies; impacts immune function significantly.
- CD4 Count: Normal range is 500-1100 cells/mm³; drops of 60-100 cells/mm³ indicate disease progression.
- Treatment: Aimed at managing viral load and preventing opportunistic infections.
Polycythemia Overview
- Polycythemia vera is a primary polycythemia stemming from a stem cell disorder.
- Characterized by elevated red blood cell (RBC) mass, also known as erythrocytosis.
- May occur with or without an increase in white blood cells (WBC) or platelets.
Primary Polycythemia (Polycythemia Vera)
- Definition: Rare blood disorder resulting from excessive red blood cell production by the bone marrow.
- Blood Characteristics: Leads to hyperviscosity, an increase in blood thickness.
- Cause: Arises from a stem cell disorder related to bone marrow dysfunction.
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Symptoms:
- Headaches and dizziness.
- Shortness of breath and itchiness, particularly after warm baths.
- Splenomegaly (enlargement of the spleen) and hepatomegaly (enlargement of the liver).
- Flushed complexion and reddened palms.
- Increased risk of thrombosis (blood clots).
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Diagnostic Tests:
- High RBC count, hemoglobin, and hematocrit levels (greater than 49% in men, greater than 48% in women).
- Typically low erythropoietin (EPO) levels.
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Treatment Options:
- Phlebotomy is used to reduce RBC count and manage hematocrit levels.
Leukemias
Acute Lymphoblastic Leukemia (ALL)
- Malignant disease of the bone marrow, involving early lymphoid precursors.
- Occurs primarily in children; 75% of cases are pediatric.
- Characterized by accumulation of malignant mature B cells in blood, bone marrow, lymph nodes, and spleen.
- Typically indolent with most cases showing slow progression; a minority may be aggressive.
- Median survival is approximately 9 years, with significant variation.
- Symptoms include asymptomatic presentations (25%), constitutional symptoms (e.g., weight loss, fever, fatigue), and lymphadenopathy (50-90%).
Acute Myeloid Leukemia (AML)
- Rapidly progressive malignancy marked by failure of myeloid cells to differentiate.
- Most common in older adults; median age at diagnosis is 65 years.
- Major risk factors include male gender, older age, smoking, obesity, and genetic conditions like Down syndrome.
- Pathogenesis involves uncontrolled growth of blasts in marrow, leading to peripheral blood blast appearance and multiple complications.
- Presence of Auer rods is pathognomonic for AML.
- Clinical issues stem from bone marrow failure, including anemia, thrombocytopenia, and increased infection risk.
- Diagnosis relies on a bone marrow aspirate revealing over 20% blast count.
- Treatment is primarily chemotherapy; survival rates vary based on response to initial treatment.
Chronic Myeloid Leukemia (CML)
- Defined by increased proliferation of granulocytic cell lines while retaining differentiation ability.
- Median age of diagnosis is 65 years; can occur across all age groups.
- Associated with the Philadelphia chromosome (Ph), resulting from a translocation between chromosomes 9 and 22, producing the BCR-ABL fusion gene.
- Often diagnosed in the chronic phase (85% of cases).
- Symptoms can be mild; may include fatigue, weight loss, and splenomegaly.
- Treated with Imatinib, which targets the BCR-ABL tyrosine kinase.
- Prognosis is favorable for those responding to treatment, with >90% six-year survival rate.
Plasma Cell Myeloma (Multiple Myeloma)
- Characterized by malignant proliferation of plasma cells producing monoclonal immunoglobulin leading to organ dysfunction.
- Median age of diagnosis is 68; more common in males.
- Clinical manifestations include bone disease with lytic lesions, anemia, bleeding complications, weight loss, infections, and hypercalcemia.
- Key renal finding includes Bence-Jones protein in urine.
- Treatment may involve autologous stem cell transplant for eligible patients.
- Median survival is between 3 to 7 years.
Hodgkin Disease/Lymphoma
- Malignant proliferation of lymphoid cells characterized by Reed-Sternberg cells.
- Bimodal incidence peaks at ages 20 and over 50; association with Epstein-Barr Virus in many cases.
- Starts in one lymph node, spreads contiguously to adjacent nodes.
- Symptoms include asymptomatic lymphadenopathy, splenomegaly, and constitutional symptoms like weight loss and fever.
Non-Hodgkin Lymphoma
- Involves malignant proliferation of lymphoid cells from progenitor, mature B cells (85%), T cells, or NK cells (15%).
- Classified into indolent, aggressive, and highly aggressive types.
- Symptoms typically involve painless lymphadenopathy and may include involvement in multiple regions.
- B-symptoms (fever, weight loss, night sweats) correlate with a worse prognosis and indicate more severe disease.
- Pancytopenia can occur when bone marrow is involved, alongside hepatosplenomegaly and potential extranodal disease spread.
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