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90 Cards in this Set

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What is anemia
Reduction in blood oxygen transport capacity, usally due to reduced circulating red blood cell mass. Reflected by low hematocrit and hemoglobin concentration
In most anemia, what does increased erythropoietin production induce
Erythroid marrow hyperplasia
What does anemia from acute blood loss reflect
Loss of blood volume (may lead to shock and death). After 4-5 days increased erythropeoietin leads to compensatory increases in marrow production (reticulocytosis)
What does anemia from chronic blood loss reflect
Results when iron reserves are depleted-iron deficiency anemia. With iron replenishment, increased marrow production (reticulocytosis) appears in several days
What are hemolytic anemias characterized by
Premature red blood cell destruction, accumulation of hemoglobin catabolites (bilirubin), and markedly increased erythropoieses with asociated reticulocytosis
What is intravascular hemolysis
Red blood cells are damaged by mechanical injury (microangiopathic hemolytic anemia) or complement (mismatched blood transfusion). Patients exhibit hemoglobinemia; hemoglobinuria; hemosiderinuria; jaundice; reduced serum haptoglobin
What is extravascular hemolysis
Occurs in mononuclear phagocytes of spleen. Predisposing factors include red blood cell membrane injury, reduced deformability, or opsonization. Manifestations are similar to intravascular hemolysis but without hemoglobinemia and hemoglobinuria
What is hereditary spherocytosis
Autosomal dominant disorder in which red blood cell cytoskeletal membrane protein defects render reythrocytes spheroidal, less deformable, and vulnerable to splenic sequestration and destruction
What is the pathophysiology of spherocytosis
Defects in several different membrane skeletal proteins can cause HS; leads to deficiencies in spectrin.
What are the characteristics of spectrin-deficient red blood cells
They have unstable membranes and lose fragments. They have diminished membrane flezibility and are trapped and destroyed in the splenic cords
What is the morphology of Hereditary spherocytosis
Spherocytic red blood cells appear small and lack central pallor. Marked congestion and prominent erythrophagocytosis in the splenic cords of Billroth. Bone marrow exhibits normoblastic hyperplasia
What are the clinical features of hereditary spherocytosis
Anemia, moderate splenomegaly, and jaundice are characteristic. Infections can trigger hemolytic crisis (massice hemolysis) or aplastic crisis (suppression of erythropoiesis by parvovirus). Gallstones develop from chronic byperbilirubinemia. Mean cell hemoglobin concentration is increased
What is glucose-6-phosphate dehydrogenase (G6PD)
An enzyme in the hexose monophosphate shunt that produces reduced glutathione, which protects the red blood cells from oxidative injury
In G6PD deficient red blood cells, what does the altered hemoglobin precipitate as
Heinz bodies, which attach to the inner cell membrane, reduce deformability, and increase susceptibility to splenic macrophage destruction. Cause both intravascular and extravascular hemolysis
Which G6PD deficiencies lead to clinically significant hemolysis
G6PD A- (10% American blacks) and G6PD Mediterranean
What is sickle cell disease
A hereditary hemoglobinopathy resulting from substitution of valine for glutamic acid, transforming Hemoglobin A to mutant S. 8% of American blacks are heterozygous
What is the sickling phenomenon
Deoxygenated HbS undergoes aggregation and polymerization into long, stiff chains that deform red blood cells
What factors influence sickling of red blood cells in Sickle Cell disease
The amount of HbS and its interaction with other hemoglobin chains in the cells. Beta-globin chains like HbF (weak interaction with HbS) and HbC (strong interaction with HbS) also influence sickling
The mean corpuscular hemoglobin concentration (MCHC). Dehydration increases MCHC, facilitating sickling
Capillary bed transit times. Usually significant deoxygenation cannot occur
What are the consequences of sickling in sickle cell disease
Chronic hemolysis--membranes become irreversibly damaged
Microvascular occlusion--hypoxia and infarction result
What is the morphology in sickle cell disease
Spleen is enlarged in early childhood. Progressive scarring and shrinkage of spleen (autosplenectomy)
Bone marrow shows normoblastic hyperplasia
Microvascular occlusions
What are the clinical features of sickle cell disease
Chronic hemolytic anemia (with chronic hyperbilirubinemia and gallstones)
Vaso-occlusive crises that present as painful episodes of ischemic necrosis
Apastic crisis due to transient suppression of erythropoiese triggered by parvovirus infection. Folate deficiency due to increased requirements
Progressive splenic fibrosis and impairment of the alternate complement pathway
What are Thalassemia syndrome
A heterogenous group of mendelian disorders characterized by defects that lead to reduced synthesis of alpha or Beta globin chains. Beta by one gene on 11, alpha by two on 16
How are beta thalassemias classified
Beta0 total absence of beta globin chains
Beta+ reduced Beta globin sysnthesis
What do the consequences of diminished synthesis of one globin chain in Thalassemia derive from
Low intracellular hemoglobin (hypochromia) and a relative excess of the other chain
What is the pathophysiology of Beta Thalassemia
Decreased Beta globin synthesis leads to excess unbound alpha chains which form aggregates that damage the cell membrane. Precursors are destroyed in the marrow or red blood cells are removed in the spleen. Marked compensatory expansion of the erythropoietic marrow. Excessive absorption of dietary iron
What is the pathophysiology of alpha thalassemia
Imbalanced synthesis ofalpha and non alpha chains. Free Beta chains for unstable tetramers that damage red blood cells and their precursors
How is Beta Thalassemia classified
Major: Homozygotes have severe, transfusion dependent anemia. Marked anisocytosis. Affects Mediterranean, Africa, Southeast Asia
Minor: Heterozygotes are asyptomatic
Intermedia: Features and severity and between the other two forms
How is alpha Thalessemia classified
Related to the number of genes deleted
Silent carrier: Single deletion, asymptomatic
Alpha-Thalassemia trait: Two gene deletions. Comparable to Beta Thalassemia minor
Hemoglobin H disease: Deletion of three alpha genes. Resembles Beta Thalassemia intermedia
Hydrops fetalis: Deletion of all four genes. Not compatible with life
What is paroxysmal nocturnal hemoglobinuria
Rare disorder characterized by chronic intravascular hemolysis. Acquired (not inherited) membrane defect. Increased sensitivity to complement-mediated lysis of RBCs. Deficiency of GPI. RBCs are hypersensitive to complement, Granulocytes, and platelet GPI proteins are predisposed to thrombosis
What is hemolysis in immunohemolytic anemias due to
Anti-red cell antibodies. Direct Coombs test is used
What is warm antibody hemolytic anemia
Idiopathic 60%. IgG anti-red blood cell coats the RBCs. Do not fix complement, but act as opsonins. Splenomegaly is characteristic.
Two models: Hapten (Antibody with drug) and Autoantibody (Drugs produce antibodies)
What is cold agglutinin immune hemolytic anemia
Anemia is caused by IgM antibodies that agglutinate red blood cells at low temperatures
Acute hemolysis occurs after infection from Mycoplasm pneumonia and Epstein Barr virus
Chronic hemolysis occurs with lymphoproliferative disorders or is idiopathic. RBC agglutiion and complement fixation below 30C
What is cold hemolysin hemolytic anemia
Occurs in paroxysmal cold hemoglobinuria and manifests as acute intermittent massive intravascular hemolysis after exposure to cold. IgG autoantibodies (Donath-Lansteiner) against P blood group antigen. Complement fixation and low temperatures, hemolysis upon rewarming. Mainly after infections from Mycoplasma pneumonia, measles, mumps, influenza
What results from significant trauma to red blood cells
Fragmentation and intravascular hemolysis. Can be from Prosthetic heart valves with turbulen flow and shear forces, or diffuse narrowing of the microvasculature owing to fibrin deposistion (DIC)
What my impaired red blood cell production be due to
Various disorders, including deficiency of a vital nutrient (Iron, vitamin B12, folate) or stem cell failure
What are megaloblastic anemias commonly due to
Deficiency of vitamin B12 or folate
What is the morphology of megaloblastic anemia
Abnormally large erythroid precursors (megaloblasts) in which nuclear maturation lags behind cytoplasmic maturation
Ineffective erythropoiesis with compensatory megaloblastic hyperplasia
Prominent anisocytosis
Abnormal granulopoiesis with giant metamyelocytes
What is the pathophysiology of Megaloblastic anemia
Deficiency of vitamin B12 or folate resulting in deranged or inadequate DNA synthesis, but normal RNA and protein synthesis. Cytoplasmic maturation is ahead of nuclear maturation. B12 and folate deficiency affects all rapidly dividing cells
What is the mechanism of B12 absorption
B12 ultimately comes from dietary animal products. Peptidic digestion releases B12, where it is bound by R binders. B12 is released in the duodenum and binds to Intrinsic Factor (IF). IF-B12 binds to receptors in the ileum. B12 complexes with transcobalamin II and is transported to tissue
What are several causes of impaired absorption of B12
Achlorhydria (elderly people): impairs vitamin B12 release from the R protein bound form
Pernicious anemia
Resection of the distal ileum
Increased requirements
What is pernicious anemia likely due to
Autoimmune response to gastric parietal cells resulting in chronic atropic gastritis and deficient IF production.
Type I antibodies block binding of B12 to IF
Type II prevent IF-B12 from binding to the ileal receptor
What is the morphology of pernicious anemia
Bone marrow: megaloblastic erythroid hyperplasia
Alimentary canal: atrophic glossitis (shiny tongue); absence of parietal cells
CNS: Lesions found in 75%, demyelination of doral and lateral cord tracts
What are the clinical features of pernicious anemia
Insidious, symptoms apear at 40-60 due to anemia and posterolateral spinal tract involvement
What are the characteristics of Anemia of Folate deficiency
Folate deficiency induces a megaloblastic anemia clinicall and hematologically indistinguishable from that seen with B12 deficiency, except that gastric atrophy and neurologic changes do not occur. Deficiency can result from inadequate intake, malabsorption syndrome, increased demand, and administration of folate antagonists
What are some general characteristics of iron metabolism
Duodenum is the primary site of absorption. Heme iron is directly absorbed, non-heme iron must be reduce to ferrous iron by cytochrome B and transported in by DMT1. Basolateral transport involves ferriportin, plasma transport involves transferrin. Excess iron is bound to ferritin and excreted in the feces
What is the etiology of iron defeficient anemia
Negative iron balance and consequent anemia can result from low dietary intake, malabsorption, excessive demand, and chronic blood loss
What is the most important cause of iron deficiency anemia in the Western world
Chronic blood loss
What are the clincal features of iron deficient anemia
Peripheral blood: Red blood cells are pale, small and cariable in shape
Marrow: Mild hyperplasia of normoblasts, but loss of sideroblasts and stainable iron in marrow macrophages
Other organs: Plummer-Vinson triad of hypochromic microcytic aemia, atrophic glossitis, esophageal webs
Describe anemia of chronic disease
Anemia is common in the setting of diverse chronic inflmmatory mediactors (TNF-alpha and IL-1), which increases the release of hepcidin from the liver Hepcidin blocks ferroportin activity on macrophages, so iron is sequestered away from erythroid progenators. Serum iron is low, but ferritin levels are high. Inflammatory mediators also reduce erythropoietin production. Anemia is normocytic/normochromic or microcytic/hypochromic
How is aplastic anemia characterized
Failure or suppression of multipotent myeloid stem cells. Neutrophenia, anemai, and thrombocytopenia result
What is the etiology of Aplastic anemia
Idiopathic 65%; Myelotoxic drugs or chemicals; dose related (benzene, alkylating agents, vincristine or busulfan); idiosyncratic (chloramphenicol, chlorpromazine, streptomycin); Hepatitis (non A, B, C, G)
What is the pathogenesis of aplastic anemia
Stem cell alterations may be due to environmental insults, drug exposure, or infections. Idiopathic may be due to primary defect in the number or function of stem cells, or suppression of altered stem cells by T cell mediated mechanisms
What is the morphology of Aplastic anemia
Hypocellular marrow (replacement by fat cells), with secondary effects due to granulocytopenia (infections) and thrombocytopenia
What are the clinical features of aplastic anemia
Insidious with symptoms related to loss of red blood cells, neutrophils, and platelets. Splenomegaly is absent. Bone marrow transplantation or immunosuppression is required
What is pure red blood cell aplasia
A form of marrow failure due to absence of red blood cell precursors. May appear acutely and transiently in chronic hemolytic states due to parvovirus infection (aplastic crisis)
What is myelophthisic anemia
Space-occupying lesions that destroy or distort the marrow architecture depress productive capacity; associated with pancytopenia and white and red blood cell precursors in peripheral blood. Metastatic cancer is the most common cause
What is anemia of diffuse liver disease primarily due to
Bone marrow failure, exacerbated by variceal bleeding or folated deficiency
What is polycythemia
Relative or absolute increase in the concentration of red blood cells in the peripheral blood. Relative may be due to decreased plasma volumes. Absolute may be due to primary (myeloid neoplasm polycythemia vera) or secondary (increased erythropoietin for physiologic or pathophysiologic sources)
What are some cuases of hemorrhagic diatheses
Increased blood vessel fragility, platelet disorders, coagulation defects, or some combo.
What are some characteristics of increased vascular fragility in bleeding disorders
Relatively common but usually do not cause serious bleeding. Petechial and purpuric hemorrhages. Caused by infections, drug reactions, poor vascular support (Ehlers-Danlos or scurvy), and Henoch Schonlein purpura (systemic hypersensitibity reaction of unknown cause)
What is thrombocytopenia
Decrease in platelet number characterized principally by petechial bleeding, most often from small vessels of skin and mucous membranes. Must be severe before bleeding become clinically evident
What are the main causes of Thrombocytopenia
Decreased production: ineffective megakaryopoiesis or generalized marrow disease
Decreased survival: immune-mediated platelet destruction with marrow hyperplasia. Drug induced (quinine, heparin) or consumption (DIC hemolytic uremic syndrome)
Sequestration: Retained in red pulp of spleen
Dilution: Massive whole blood transfusions
What is immune thrombocytopenia purpura
Two forms of antibody mediated platelet destruction
Acute: Self limited after viral infection of rubella, cytomegalovirus, hepatitis, monomucleosis
Chronic: Platelet autoantibodies against IIb/IIIA or Ib/IX. Splenectomy benefits 75-80%
What are the clinical features of immune thrombocytopenia purpura
Women of childbearing age; long history of bruising or nosebleeds, but can be sudden onset. Subarachnoid or intracerebral hemorrhage is rare but serious
What is the morphology of immune thrombocytopenia purpura
Spleen is normal size but shows sinusoidal congestion and prominent germinal centers. Bone marrow megakaryocyte numbers are increased
What are the characteristics of drug-induced thrombocytopenia
Many drugs can act as hapten or participatin in the formation of immune complexes that deposit on platelet membranes. Drug induced antibodies cause removal of platelets via the reticuloendothelial system and result in bleedin gsymptoms. Withdrawal of the offending drug leads to clinical improvement
What are the characteristics of Thrombotic Thrombocytopenic purpura and hemolytic uremic syndrome
Related disorders within the spectrum of thrombotic microangiopathies characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, transient neurological deficits (TTP), or renal failure (HUS). Usually due to widespread hyaline microthrombi in arterioles and capillaries composed of platelets and fibrin
What is the pathophysiology of Thrombotic thrombocytopenic purpura
Deficiencies in ADAMTS13, a serum metalloprotease that limits the size of von Willebrand factor. In its absence, high molecular weight vWF promotes platelet aggregation throughout the microcirculation
What is the pathophysiology of Hemolytic Uremic Syndrome
Follows gastrointestinal infections with verotoxin-producing E. coli. Injures endothelial cells and promotes dysregulated platelet activation and aggregation
What is the epidemiology of Thrombotic thrombocyopenic purpura and hemolytic uremic syndrome
TTP affects women; HUS affects children and the elderly during food poisoning outbreaks
How are hemorrhagic disorders related to defective platelet function characterized
Prolonged bleeding time in association with normal platelet count
What are common congenital disorders of hemorrhagic disorders related to defective platelet functions
Defective platelet adhesion: Bernard-Soulier syndrome caused by deficient GbIb/IX, the receptor for vWF
Defective platelet aggregation: Thrombasthenia caused by deficient GpIIb/GpIIIa, which is involved in binding fibrinogen
Disorders of platelet secretion: Initial aggregation with collage or ADP is normal, but subsequent platelet responses are impaired (secretion of prostaglandins and granule-bound ADP)
What acquired disorders are clinically significant in hemorrhagic disorders related to defective platelet functions
Aspirin ingestion: Suppresses the synthesis of thromboxane A2, necessary for platelet aggregation
Uremia: Defects in platelet function
How does bleeding in patients with clotting factor abnormalities differ from that encountered in patients with platelet deficiencies
Spontaneous appearance of petechiae or purpura is uncommon; instead, there will be large ecchymoses or hematomas after injury or prolonged bleeding after laceration or surgery
Bleeding into gastrointestinal and urinary tracts and weight-bearing joints is common
What are acquired deficiencies of clotting abnormalities associated with
Multiple clotting abnormalities. Vitamin K deficiency causes depresses synthesis of factors II, VII, IX, and X and protein C. Parenchymal liver disease causes hemorrhagic disease
What do hereditary deficiencies of clotting abnormalities typically affect
A single clotting factor. The most common factors are Hemophilia and von Willebrand disease
What is one component required for factor X activation in the intrinsic coagulation pathway
Factor VIII procoagulant protein. Deficiency causes classic hemophilia A
What are the categories of von Willebrand disease
Type 1 and 3: reduced levels of vWF. 1 is dominant and most common, quite mild. 3 is severe but uncommon recessive
Type 2: dominant, caused by reduced amount of the intermediate and large vWF multimers
Why are levels of factor VIII often reduced in von Willebrand disease
vWF stabilizes factor VIII in circulation. Reflected by prolonged bleeding time despite normal platelet numbers and prolonged partial thromboplastin time
How does von Willebrand disease most often present
Spontaneous bleeding from mucous membrane, excessive bleeding from wounds, and menorrhagia. Except for type 3, factor VIII levels are only modestly depressed. Symptoms of hemophilia, such as bleeding into the joints, are uncommon
What is factor VIII deficiency
Hemophilia A. X-linked recessive, reduced amount of active factor VIII. Clinical features only seen in severe deficiency. Post traumatic bleeding may be excessive. Associated with:
Massive hemorrhage after trauma
Spontaneous hemorrhages in joints
Absence of petechiae
Prolonged partial thromboplastin time and normal bleeding time. Treat with replacement therapy
What are the categories of von Willebrand disease
Type 1 and 3: reduced levels of vWF. 1 is dominant and most common, quite mild. 3 is severe but uncommon recessive
Type 2: dominant caused by reduced amount of the intermediate and large vWF multimers
What is Factor IX deficiency
Hemophilia B or Christmas disease, X-linked recessive. Clinically indistinguishable from Hemophilia A
What is Disseminated intravascular coagulation
Acute, subacute, or chronic thrombohemorrhagic disorder occuring as a secondary complication in a variety of diseases. Characterized by activatino of the coagulation sequence, leading to microthrombi throughout the microcirculation. Consumption of platelets, fibrin, and coagulation factors, leading to activation of fibrinolytic mechanisms
How may Disseminated intravascular coagualtion present
Signs and symptoms relating to infarction caused by microthrombi
Hemorrhagic diathesis result from activation of fibrinolytic mechanisms and depletion of elements required for hemostasis
What is the pathogenesis of Disseminated intravascular coagulation
Triggered by release of tissue factor or thromboplastic substances into the circulation, and widespread endothelial circulation
What sources can tissue factor or thromboplastic substances released into the circulation be derived from in DIC
Placenta, granules of leukemic cells, mucus release from adenocarcinomas, bacterial endotoxins activating release of IL-1 and TNF-alpha
How does endothelial injury initiate DIC
It causes tissue factor release from endothelial cells, promoting platelet aggregation, and by activating the intrinsic coagulatino pathway by exposing subendothelial connective tissue
What is the morphology of DIC
Microthrombi, with infarctions and hemorrhages, found in:
Kidneys, Lungs, Brain, Adrenals, and Placenta
What are the clinical features of DIC
50% in obstetric patients, 30% with carcinomatosis. Sepsis and trauma for the rest. Onset can be fulminant or insidious.
Microangiopathic hemolytic anemia resulting from widespread microvascular occlusion
Respiratory symptoms
Neurologic signs and symptoms, including convulsions and coma
Oliguria and acute renal failure
Circulatory failure and shock