Hematopoietic Flashcards
Define: Leukopenia Granulocytopenia Aplastic Anemia Agranulocytosis
Leukopenia - decrease in WBC
Granulocytopenia - low granulocytes
Aplastic Anemia - deficiency in bone marrow maturation of all cell types from stem cells
Agranulocytosis - absence of neutrophils
Neutropenia: cause
Congenital - alloimmune neonatal neutropenia, cyclic neutropenia, kostmann syndrome
Acquired - secondary to lupus, infection, drug related, radiation therapy, hematologic malignancies
Autoimmune - primary is rare
Neoplasms
Neutropenia: mechanisms of symptom production
Because neutrophils are the first line of defence
Skin infection, ulcerative necrotizing lesions of the mouth, infection of the respiratory tract
Neutrophils elaborate proteolytic enzymes to liquefy dead cells
No signs of inflammatory response, fever assumed to be infectious in origin, absence of pus
Infectious Mononucleosis
Self limiting lymphoproliferative disorder caused by Epstein Barr virus
Adolescents and young adults in developed countries
Persists for the life time and invades 90% of people
Spread: oral secretions, close contact, kissing, crowded conditions
Infectious Mononucleosis: Pathogenesis
Virus penetrates nasopharyngeal, oropharengeal, and salivary epithelial cells
Spreads to underlying oropharyngeal lymphoid tissue and B lymphocytes - receptors for EBV
Infection of the B cells may kill the B cell or may incorporate into the genome
Infected cells proliferate in circulation and produce heterophil antibodies
Virus specific T cells appear as large atypical lymphocytes
Healthy persons response is to control viral shedding by limiting th number of affected cells rather than eliminating them
Infected cells disappear after recovery, but virus remains in transformed B cell and is shed in saliva
Infectious Mononucleosis: manifestations
Insidious onset - incubation from time of expose to symptoms is 4-8 weeks Malaise Anorexia Chills Fever Pharyngitis Lymphadenopathy Enlarged lymph nodes Hepatitis and splenomegaly are common Leukocytosis is common
Acute phase is 2-3 weeks
Complications - rupture of spleen, cranial nerve pansies, encephalitis, meningitis, transverse myelitis, guillain barre syndrome
Leukemia
Malignant neoplasms of cells derived from the precursor myeloid or lymphoid tissue cells
Reversal of ratio of RBC to WBC
Immature and poorly differentiated
Longer life span
Proliferate rapidly in the blood stream
Abnormal function
Interfere with normal maturation of cells
Leukemia: Causes
Largely unknown Radiation exposure Benzene Antitumor drugs Post chemotherapy Genetic predisposition - Down syndrome, neruorfibromatosis
Acute Leukemia: manifestations
Cancers of the hematopoietic progenitor cell
Low grade fever Night sweats Weight loss Infections Bleeding and easy bruising Lymphadenopathy Splenomegaly and hepatomegaly Symptoms of depressed bone marrow Leukostasis - high number of circulating leukemic blast cells increasing blood viscosity Hyperuricemia - uric acid accumulation secondary to cell death
Acute Lymphocytic Leukemia
Common form in children
Immature lymphocytes and their progenitors that originate in bone marrow, but infiltrate spleen, lymph nodes, CNS, etc
Most of B cell origin
Over production of abnormal immune cells and decreased production of other cell types
Chromosomal aberrations dysregulate expression and function of factors of normal hematopoietic cell development
Acute Myelocytic Leukemia
Disease of older adults
Pluripotent myeloid stem cells in bone marrow and interfere with maturation of all blood cells
Over production of abnormal erythrocytes and granulocytes with a decrease in production of all other cell types
Associated with acquired genetic alterations inhibiting terminal myeloid differentiation - bone marrow is replaced with undifferentiated blast cells
Leading to anemia, neutropenia, thrombocytopenia
Chronic Leukemia
Affects adults
Insidious onset
Proliferation of more fully differentiated myeloid and lymphoid cells
Chronic Lymphocytic Leukemia
B lymphocyte malignacy
Adults
Minimal symptoms or rapid and fatal
Often asymptomatic Elevated lymphocytes Lymphedema Hepatosplenomegaly Fever Abdominal pain Weight loss Progressive anemia Thrombocytopenia Rapid rise in lymphocyte count Hypogammaglobulinemia - increased susceptibility to infection
Chronic Myelogenous Leukemia
Disorder of pluripotent hematopoietic progenitor cell
Excessive proliferation of marrow granulocytes, erythroid precursors and megakaryocytes
Cytogenetic abnormality - Philadelphia chromosome
Phases:
Chronic - slow with non specific symptoms
Leukocytosis with immature granulocytes in peripheral blood
Anemia and thrombocytopenia develop
Typically asymptomatic with splenomegaly common at dx
Short accelerated - enlargement of spleen and progressive symptoms
Feeling of abdominal fullness and discomfort
Increase in basophils count and immature cells in blood or bone marrow
Low grade fever, night sweats, bone pain, weight loss, bleeding, bruising
6-12 months
Terminal - evolution to acute leukemia
Increasing number of myeloid precursors, blast cells
Constitutional symptoms become more pronounced and splenomegaly increases significantly
Isolated infiltrates can involve skin, lymph nodes, bone, and CNS
Very high blast counts - leukostasis
Median survival 3months
Non-Hodgkin Lymphoma
Originates in lymphatic tissue or nodes (T and B lymphocytes)
Slow growing painless lymphadenopathy
May transform into more aggressive forms of lymphoma or leukemia
Indolent:
Painless; can be isolated or widespread
Involved lymph nodes may present in the retroperiotneum, mesentry, and pelvis
Disseminated at the time of dx and bone marrow involvement is common
Aggressive:
Accompanying constitutional symptoms
Fever, drenching night sweats, weight loss
Increase susceptibility to bacterial, viral, and fungal infections associated with hypogammaglobulinemia and poor humoral antibody response NOT cellular
Hodgkin Lymphoma
Lymph node enlargement above diaphragm Night sweats Pruritus Fever Chills Weight loss Fatigue Anemia Susceptibility to infection
Multiple Myeloma:
Plasma cell dyspraxia in bone marrow and osteolytic bone lesions throughout the body
Main sites are bone and bone marrow
Abnormal proliferation of marrow plasma cells
Activation of osteoclasts leading to bone reabsorption and destruction and prone to infection due to impaired cell production
B cell malignancy of terminal differentiated plasma cells
Multiple Myeloma: manifestations
Bone reabsorption - fractures and hypercalcemia
High concentrations of paraproteins - hyperviscosity of blood
Paraprotiens breakdown into amyloid - HF and nephropathy
Myeloma nephrosis
Normal immunoglobulin depression - bacterial infections
Plasma cell tumors - bone destruction and bone pain
Anemia and suppression of cell production
Symptoms of bone marrow suppression
Weight loss and weakness
Hemostasis and coagulation cascade
- Vessel Spasm
Injury to blood vessel causes vascular smooth muscle contraction to reduce blood flow
Both local and neural reflexes and local humoral factors released from platelets contributing to vasoconstriction - Formation of platelet plug
Von willebrand factor is released from endothelium and bonds to platelet receptor causes adhesion to exposed collagen
Adherence causes activation and release of ADP and TXA2 to attract more platelets leading to aggregation
3.Blood coagulation
Sequential activation of factors in blood
A) intrinsic - initiated by activation of factors XII
B) extrinsic - activated by tissue factor that is exposed on tissue injury
Both pathways lead to activation of factor X and the conversion of prothrombin II to thrombin IIa and the conversion of fibrinogen I into insoluble fibrin Ia
- Clot retraction
Actin and myosin contract pulling platelets and squeezing out plasma causing shrinkage - Clot dissolution or FIbrinolysis
FIbrinolysis
Plasminogen is converted by plasminogen activators into plasmin
Plasmin digest fibrin strands and certain clotting factors
Tissue type plasminogen activator tPA - endothelial cells - active when attached to fibrin
Urokinase type plasminogen activator uPA - present in tissues - activates plasminogen in the fluid phase
Excess circulating plasmin is inactivated by a2-antiplasmin limiting fibrinolytic process to the local clot
Endothelial cells modulate coagulation and anticoagulation by releasing PA inhibitors which block FIbrinolysis and confer overal procoagulation
Coagulation Factors
Vitamin K - synthesized in liver - needed for synthesis of VII IX and X, prothrombin and proteins C and S
Calcium (factor IV) is required in all by the first two steps
Circulate as inactive factors
Hypercoaguability: Increased Platelets (thrombocytosis)
Predisposes to platelet adhesion, formation of platelet clots, and disruption of blood flow
Increase in platelet count, disturbances in blood flow, damage to vascular endothelium, increased sensitivity of platelets to factors that cause adhesion
Reactive disorder - associated with iron deficiency anemia, splenectomy, cancer, chronic inflammatory conditions
Myeloproliferative Disorders - excess platelets that predispose to thrombosis or bleeding when the rapidly produced platelets are defective
Acquired genetic anomaly, polycythemia Vera
Hypercoaguability: Increased Clotting Activity
Thrombus formation due to activation of the coagulation system can result form disorders affecting coagulation
Primary. - mutations in factor V and prothrombin predisposing to venous thrombosis and elevated prothrombin levels
Secondary - Stasi of blood and accumulation of platelets in persons with bedrest, sickle cell disease, oral contraceptives, pregnancy, malignancies
Hypercoaguability: endothelial damage
Hypercoaguability: decreased anticoagulation factors
Platelet adherence due to elevated lipids, smoking
Atherosclerotic plaques disturb blood flow causing endothelial damage and promoting platelet adherence
Hemophilia A
Mutation of factor VIII gene = defective
Bleeding can be spontaneous and severe
Bound to Von Willebrand Factor until an injury damages blood vessels
In response to injury, coagulation factor VIII is activated and separates from vWF
Active factor interacts to turn X into Xa = formation of a stable clot
Thrombocytopenia: manifestations
Decrease in the number of circulating platelets
Spontaneous bleeding
Bruising
Purpura - cutaneous bleeding
Petechiae - pin point hemorrhage
Von Willebrand Disease
Deficiency or defect in vWF = defect in platelet function and coagulation pathway
Alters platelet receptors to stimulate adhesion to collagen and attraction of more platelets = platelet plug
Normal platelet count
Alters platelet receptors to stimulate adhesion to collagen and attraction of more platelet
Vascular Disorder Bleeding
Weak vessel walls or damage to vessel walls leads to
Easy bruising
Petechiae and purpura
Vitamin C deficiency - poor collagen synthesis and failure of capillary beds to be cemented together
Cushing - protein wasting and loss of blood vessel tissue support because of excess cortisol
Acute Disseminated Intravascular Coagulation
Activation of coagulation sequence from other disorder
Massive activation leads to fibrin deposits and thrombus formation
Leading to ischemia, hemolytic anemia from fragmented RBC
Consumption of platelet and coagulation factors and activation of plasminogen
Leads to hemorrhagic diathesis
Trauma, sepsis, cancer, endothelial damages and activation of factor XII (stasis, temperature extremes, virus, infection, immune), reduced antithrombin and protein C
Bleeding and microemboli
Anemia: Causes
Blood loss
Hemolysis
Deficient RBC production - bone marrow deficiency, lack of nutritional elements
Blood Loss Anemia: mechanisms of blood loss and manifestations
Rapid:
Symptoms initially due to loss of intravascular volume, CV collapse, hypoxemia, shock
Fall in RBC count caused by hemodilution resulting from movement of fluid in the vascular compartment
Fatigue, altered mentation, Tachypnea, SOB ,dyspnea, tachycardia, BP changes, chest pain, oliguria, pale cool skin, cyanosis
Slow/Chronic:
Results from deficiency in iron with depleted iron stores
Often due to GI bleeding, mensutral disorders
Doesn’t affect blood volume
Often asymptomatic
Hemolytic Anemia: mechanisms of blood loss and manifestations
Premature destruction, retention of iron and compensatory increase in erythropoiesis
Normocytic and mormochromic
Intrinsic to RBC - sickle cell, thalassemia
External to RBC - toxin, infection, trauma
Destruction in vascular compartment - mechanical injury due to defective valves
Destruction in phagocytic cells of reticuloendothelial system - within phagocytic cells of spleen and liver
Fatigue, dyspnea, signs of impaired oxygen transport, jaundice, pigment gall stones, splenic sequestration
Sickle Cell Anemia
Inherited Abnormal hemoglobin leads to chronic hemolytic anemia, pain, and organ failure
Mutation in the beta chain of the hemoglobin molecule with the abnormal substitution of amino acid
Predisposing factors African Cold Stress Physical exertion Infection Illness causing hypoxia, dehydration, acidosis
Results in::: Chronic hemolytic anemia Blood vessel occlusion Sickle cell crisis Pulmonary infection Cerebral infection Splenic sequestering crisis
Deficient production of RBC: Iron deficiency Anemia
Deficiency leads to increased hemoglobin synthesis
Causes
Dietary deficiency, increased demands (pregnancy), blood loss
Symptoms
Pallor, fatiguability, dyspnea, tachycardia, brittle hair and nails, smooth tongue, sores in corner of mouth, dysphagia, decrease in acid secretion
Pica - abnormal eating of ice, dirt, etc (neurological or chemical imbalance)
Deficient Production of RBC: Megaloblastic Anemia
Deficiencies in vit b12 or folic acid
Causes
Inflammation, neoplasms, gastric issues, dietary deficiency
Vitamin B12 deficiency anemia - pernicious anemia resulting from strophic gastritis: immunologically mediated destruction of gastric mucosa preventing B12 absorption
Folic acid deficiency anemia - megaloblastic RBC changes
Lost in cooking, malnutrition, dietary lack, alcoholism
Relationship of folic acid and vitamin b12 to megaloblastic Anemia
Without vit b12 and folic acid DNA cannot be synthesized and nuclear maturation leading to RBC maturation and division cannot occur
Aplastic Anemia
Causes: Radiation, chemical, toxins Chemo Virus Idiopathic anemia
Chronic Diseases Associated with Anemia
Infections - AIDS, osteomyelitis
Cancers
Autoimmune - RA, LUpus, IBS
Chronic Kidney Disease - erythropoietin deficiency
Polycythemia: manifestations
Abnormally high total RBC count with hematocrit greater than 50%
Related to increases in blood volume and viscosity that lead to HTN and stagnation of blood flow
Polycythemia: relative and absolute
Relative - hematocrit rises because of loss of plasma volume without a corresponding increase in RBC
Water deprivation, excess use of diuretics, GI losses
Absolute - rise in hematocrit due to increase in total RBC mass
Polycythemia: primary vs secondary
Primary - Neoplastic disease of pluripotent stem cells of bone marrow charecteristics by increase in total RBC mass accompanies by elevated WBC and platelet counts
Secondary - results from physiologic increase in the level of erythropoietin compensatory to hypoxia
Living at high altitudes, chronic heart and lung disease, smoking, erythropoietin secreting neoplasms
