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Flashcards in Hematopoietic Deck (41)
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Aplastic Anemia

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



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
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



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
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
Bleeding and easy bruising
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
Minimal symptoms or rapid and fatal

Often asymptomatic
Elevated lymphocytes
Abdominal pain
Weight loss
Progressive anemia
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

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

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

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
Weight loss
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

1. 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

2. 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

4. Clot retraction
Actin and myosin contract pulling platelets and squeezing out plasma causing shrinkage

5. Clot dissolution or 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
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
Deficient RBC production - bone marrow deficiency, lack of nutritional elements


Blood Loss Anemia: mechanisms of blood loss and manifestations

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

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
Physical exertion
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

Dietary deficiency, increased demands (pregnancy), blood loss

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

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

Radiation, chemical, toxins
Idiopathic anemia


Chronic Diseases Associated with Anemia

Infections - AIDS, osteomyelitis
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