Quiz Questions 2 Flashcards
(17 cards)
Elemental iron is usually absorbed via the proximal small bowel. First the ferric (Fe+3) form of iron must be converted the ferrous (Fe+2) form of iron. This conversion is helped along by the presence of an acidic milieu. An enzyme ferrireductase located in the brush border of the intestine, also converts the ferric to ferrous iron, which allows it to bind to its transporter protein within the intestinal cell membrane. The transfer of iron across the intestinal cell membrane is facilitated by DMT-1 (divalent metal transporter protein) and then iron is transported in the plasma by the carrier protein transferrin (2 iron molecule are carried on each transferrin molecule).
True or False. A patient undergoing total gastrectomy is expected to have normal iron absorption.
false
The pH of the proximal small bowel is largely dependent upon the dumping of gastric acid through the pyloric valve into the duodenum. It is this gastric acid which lowers the pH and facilitates the reduction of Fe+3 to Fe+2. If the stomach is removed, no gastric acid is available to lower the pH of the proximal small bowel and as a consequence iron is not absorbed normally. In this setting treating the patient with ascorbic acid will often permit medicinal iron to be absorbed in quantities high adequate to replace depleted iron stores. If this is not successful, patients may require parental iron replacement.
Normal RBCs survive in the circulation for approximately 100-120 days. During the time a RBC circulates it is repeatedly passing through the sinusoids of the spleen and liver and bone marrow traversing the endothelium.
True or False. In a fashion similar to platelets, normal RBCs are removed from the circulation randomly. This removal is dependent primarily upon the frequency that a RBC interacts with the endothelial cell surface and the macrophage.
false
Normal RBCs survive in the circulation for approximately 100-120 days. During the time a RBC circulates it is repeatedly passing through the sinusoids of the spleen and liver and bone marrow traversing the endothelium. Normal RBCs are removed from the circulation according to their age. Aged (senescent) RBCs are not able to protect themselves from oxidative stress and are preferentially removed from the circulation. The RBCs are removed by tissue macrophages (also called reticulo-endothelial cells). As RBCs age they accumulate IgG immunoglobulin on their surface. In the presence of membrane-bound IgG, the RBC becomes vulnerable to scavenging by the macrophages.
Causes of Non-immunologically mediated hemolysis include disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), vasculitis (eclampsia, autoimmune), and march hemoglobinuria/Marathoners hemolysis.
True or False. The hallmark of non-immune mediated hemolysis in a peripheral blood smear is the occurrence of spherocytes because the mechanism of their formation is similar as that seen in cold hemolytic anemia.
false
It is characterized by the presence of schistocytes caused by the shearing of RBCs and fibrin consumption within small blood vessels, over intravascular devices like heart valves or ventricular assist devices, and due to pressure from bone of the feet when running.
Immune hemolytic anemias can be categorizes according to their reactivity by temperature. Cold reactive antibodies are antibodies which bind to the RBC surface and activate complement at temperatures below body temperature.
True or False. A characteristic of cold reactive antibody mediated hemolysis is the presence of spherocytes in the peripheral blood smear.
false
Warm IgG-mediated immune hemolysis is characterized by the presence of spherocytes in the peripheral blood. The spherocytes are formed are present because the RBCs loose a portion of their membranes as the antibody and/or complement coated RBC is assaulted by macrophages in the sinusoids of the RES. Cold-reactive hemolysis is characterized by red cell agglutination on a peripheral blood smear. It usually caused by cold-reactive IgM that fixes complement on the red cell surface and lysis the RBC in the blood vessel. The IgM is often directed against the I antigen. In the setting cold reactive hemolysis the determination of “cold agglutinin titers are often useful. Cold agglutinin titers reflect the ability of the cold reactive antibody to cause RBCs to agglutinate at temperatures below body temperature. The titer is the maximum dilution of plasma in which agglutination can still occur. In general, cold agglutinin titers greater than 1:64 are abnormal.
Tests that infer a hemolytic process to be immune-mediated include the direct (direct antiglobulin test; DAT) and indirect Coombs’ (indirect antiglobulin test; IDAT) test. In the direct Coombs’ test, washed human RBCs are incubated with rabbit anti-human IgG or rabbit anti-complement antibodies (Coombs’ reagent) and the degree of visible RBC agglutination graded by the laboratory technician. The indirect Coombs’ test is done by incubating normal RBCs to patient serum, adding a Coombs’ reagent, and grading the degree of agglutination observed. In contrast to the direct tests, which detect IgG or C3d on the red cell surface, this test detects target protein in the patient serum. Unlike the direct Coombs’ test, the indirect test is only rarely used to diagnose a medical condition. More often, it is used to determine whether a person might have a reaction to a blood transfusion.
True or False. The grading of the degree of RBC agglutination in the direct Coombs’ test of great clinical importance, since the clinician can infer from these results that the immune hemolytic episode can be expected to be severe and difficult to treat.
false
The degree of agglutination does not correlate with the severity of hemolysis nor the response to appropriate intervention.
Hemolytic anemia can be categorized as being either intravascular or extravascular. During intravascular hemolysis RBCs are destroyed within the lumen of blood vessels; in this setting, free Hb is released into the plasma, bound by haptoglobin, the haptoglobin-Hb complex is removed by the reticuloendothelial system, and non-bound Hb excreted in the urine.
True or False. In contrast, during extravascular hemolysis the RBC is removed by the spleen. For this reason, the haptoglobin is never decreased during intravascular hemolysis and, therefore, a decrease in haptoglobin concentrations can be used to reliably tell the difference between intravascular and extravascular hemolysis.
false
The haptoglobin in commonly depressed in both intravascular and extravascular hemolysis, therefore, the finding of a decreased haptoglobin cannot be used to reliably differentiate between intravascular and extravascular hemolysis. During a brisk intravascular, partial phagocytosis of RBCS and inability of the liver to appropriately process the Hb load may result in “leakage” of free Hb back into the plasma resulting in the decrease in haptoglobin via the formation and removal of haptoglobin-Hb complexes.
Compared to other types of anemia, hemolytic anemia is relatively unusual. It is important to remember that often hemolytic anemias occur in combination with other forms of anemia (e.g. warm autoimmune hemolytic anemia + anemic of chronic disease). The presence of hemolytic anemia should always be suspected if a patient has unexplained jaundice (especially if it is predominantly due to unconjugated bilirubin) or unexplained drop in the Hb concentration (but always remember that the removal of senescent RBCs is accelerated during infection, fever, or inflammation) or an elevated reticulocyte count (without evidence of blood loss or recent re-establishment of adequate nutritional status).
True or False. A common way of inferring the presence of hemolytic anemia is to evaluate the LDH and haptoglobin. If the LDH and haptoglobin are both elevated in the absence of other explanations there is a reasonable indication that hemolysis is occurring.
false
The presence of hemolytic anemia should always be suspected if a patient has unexplained jaundice (especially if it is predominantly due to unconjugated bilirubin) or unexplained drop in the Hb concentration (but always remember that the removal of senescent RBCs is accelerated during infection, fever, or inflammation) or an elevated reticulocyte count (without evidence of blood loss or recent re-establishment of adequate nutritional status). When hemolysis is present the LDH (a ubiquitous intracellular enzyme) and the total in indirect bilirubin are usually elevated. Haptoglobin binds Hb that is free in plasma. The reticuloendothelial system removes the haptoglobin-hemoglobin complex from the body. A decrease in haptoglobin supports a diagnosis of hemolytic anemia, especially when correlated with a decreased RBC count, Hemoglobin, and Hematocrit, and also an increased reticulocyte count. The combination of a decreased haptoglobin and elevated LDH are highly specific (95%) and sensitive (95%) for the presence of hemolysis. If only one of the haptoglobin is low or the LDH elevated the sensitivity and specificity declines to 50%, respectively. If both tests are normal, there is
Cold reactive hemolysis is characterized by red cell agglutination on a peripheral blood smear. It is usually caused by the reactivity of a cold-reactive IgM antibody to a RBC surface antigen. The IgM, being a large antibody, tends to cause the complement fixation process to progress to “completion” in which the terminal attack complex of complement is able to violate the cell membrane resulting to intravascular hemolysis.
True or False. The treatment of choice for cold reactive hemolysis is the ablation of the spleen by either splenectomy or embolization of the spleen. In this way, less RBCs are removed from the circulation and the survival of RBCs is increased to acceptable levels.
false
Since cold reactive IgM antibodies cause intravascular hemolysis rather than extravascular hemolysis, ablation of the spleen is ineffective. Likewise, the use of corticosteroids (it is postulated that a mechanism of their action may be inhibition of phagocytosis) are not effective. Recent evidence indicates that the anti-CD20 monoclonal antibody rituximab may be useful for the treatment of this disorder, if the avoidance of cold exposure is not successful and the disorder is severe enough to warrant this level of intervention.
The term “thermal amplitude” refers to the variation in reactivity according to temperature of some antibodies with their targets on RBCs. This is of clinical importance, since the thermal amplitude can be important when patients undergo surgical procedures requiring cardioplegia (where the heart surgery is done while the heart is stopped and under cold conditions) or receiving non-warmed intravenous infusions of blood products or solutions. Also, patient with cold agglutinins may be hemolyzed when they are exposed to cold ambient temperatures.
True or False. It may be important to keep a patient with cold agglutinin disease at a temperature less than the thermal amplitude.
false
Since Cold reactive IgM binds to RBCs at temps less than body temperature, once bound they cause the incomplete or complete fixation of complement. As the temperature rises the IgM may elute from the RBC and complement fixation is not completed and no hemolysis occurs. Thermal amplitude refers to the highest temperature in which RBC agglutination, hemolysis or antibody binding is detected. Patients should be kept at a temperature > the thermal amplitude. This is particularly critical during cardioplegic surgery where ambient temperatures in the OR are kept below normal body temperature.
Thalassemias are quantitative deficiencies of either the alpha or beta chains of the hemoglobin molecule. The most severe form of beta-thalassemia (which can be caused by >150 different mutations) is characterized by extra-medullary hematopoiesis, chronic hemolysis, iron overload with iron deposition, and splenomegaly.
True or False
true
The imbalance of globin chain production causes decreased Hb amount in each RBC. The excessive production of one globin chain results in its precipitation in the RBC leading to damage to the RBC precursors and circulating cells, intra- and extravascular hemolysis and ineffective erythropoiesis.
Hydroxyurea is a chemotherapy agent usually used to treat hematological malignancies which reduces the number of painful episodes and the rate of other complications associated with sickle cell disease. Hydroxyurea does protect the body from the damaging effects of sickled RBCs primarily by transforming endothelial cells in such a way that the sickled RBCs no longer adhere to their surface and vaso-occlusion no longer occurs.
True or False
false
Hydroxyurea (and other drugs which are not practical to use in the sickle cell population) has the capacity of increasing fetal Hb (Hb F) production. This increase in Hb F concentration in each RBC prevents the sickling of the RBC, increases blood flow through the capillaries, and prevents vaso-occlusion. Increased Hb F results in an increase of RBC survival from 15-30 days (in patients with Hb SS) to 60-90 days (when the Hb in the RBCs become HbSS/HbF). A normal RBC lives about 90-120 days in the circulation.
The osmotic fragility test is diagnostic of hereditary spherocytosis.
True or False
false
Hereditary spherocytosis (HS) is a congenital disorder of autosomal inheritance. Patients typically present with chronic, compensated hemolysis, pigmented gallstones, and splenomegaly. Examination of the peripheral blood smear shows the presence of spherocytes. This disorder has a clinical course similar to that of hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HP). All of these disorders have defects in the cytoskeleton of the RBC which allow the affected RBCs to take on the shape of spherocyties (HS), elliptocytes (HE) or strange shaped cells (HP). The defective RBCs are removed in the spleen and for this reason, in severe cases; splenectomy may be effective in reducing hemolysis and its complications. Red cell aplasia may occur secondary to folate deficiency or parvovirus B19 infection. The osmotic fragility test detects the ease in which RBCs are lysed in increasingly dilute aliquots of NaCl solution. Spherocytes from any cause (e.g. warm auto-immune hemolytic anemia) are detected by the osmotic fragility. For this reason, this test is not diagnostic of HS. An abnormal osmotic fragility test must be interpreted in the clinical context of the patient.
Sickle cell disease (SCD) is characterized by homozygous HbS (sickle cell anemia) or coinheritance of HbS with other Hb abnormalities (most commonly HbSC or S/beta thalassemia). The hallmark features of SCD are chronic hemolysis and episodic vaso-occlusion, acute vaso-occlusive pain crises, acute chest syndrome, acute on chronic anemia, and splenomegaly.
True or False
false
The chronic hemolysis and episodic veno-occlusion of sickle cell disease is characterized by adhesion of sickle reticulocytes to post-capillary venules, hypoxia, sickling of the RBC, ischemia, necrosis, and end-organ damage. The acute vaso-occlusive pain crises (which are the hallmark of the disease) are characterized by intense, unpredictable acute pain in bones and joints and are treated with parenteral opiates and other supportive measures. The acute chest syndrome is an acute lung injury syndrome likely caused by fat embolism from the bone marrow, infection or intrapulmonary sickling and presents like pneumonia. It is treated with transfusion, antibiotics and other supportive measures. Patients may develop aplastic crises from parvovirus B19 infection in childhood and develop acute anemia from bone marrow suppression together with chronic anemia. Splenic infarction in childhood (due vaso-occlusive disease) leads to a small atrophic and non-functioning spleen (autosplenectomy) in almost all patients with HbSS. This causes a susceptibility to pneumococcal sepsis and sepsis from other encapsulated organisms. Thus, splenomegaly is not a hallmark of the disease. Exceptions are patients with HbSS and HPFH or patients with compound heterozygosity for HbS and other hemoglobins (such as HbC or beta thalassemia). These patients may retain their spleen throughout adulthood and even suffer from splenomegaly.
Paroxysmal hemoglobinuria is a hereditary disease characterized by episodes of extra-vascular hemolysis and hemoglobinuria.
True or False
false
Paroxysmal hemoglobinuria (PNH) is an acquired disorder in which the phosphatidylinositol glycan (PIG) linkages for key cell surface proteins are missing from the cell surface. Among the proteins usually attached to the PIG linkages are CD55 and CD59 which normally prevent complement mediated hemolysis. In the absence of CD55 and CD59, the affected RBCs undergo complement-mediated intravascular hemolysis characterized by hemoglobinuria, a predisposition to venous and arterial thrombosis, renal failure, and profound fatigue. The diagnosis is made by doing a flow cytometric analysis of the patient’s peripheral blood for the absence of CD55 and CD59 on RBCs, granulocytes, and monocytes.
Hemoglobin switching refers to the change in globin chain production from the neonatal period to postnatal period. This change consists of the “switching” in production of the alpha and beta chains in the postnatal period with the alpha chain replacing the beta chain in adult hemoglobin.
True or False
false
The term “Hb switching” refers to the substitution of the gamma globin chain found in fetal Hb (alpha2, gamma2) by the beta chain found in adult Hb (alpha2, beta2). Typically, gamma chain production begins to decrease and beta chain production begins to increase at about 30 weeks of gestation. 2-3 months after birth beta chain production supercedes that of the gamma chain and adult Hb begins to replace fetal Hb. This is an important phenomenon since diseases which affect the beta globin chain (eg sickle cell) may not be evident at birth.
Hemoglobinopathies are qualitative disorders of portions of the hemoglobin molecule due to amino acid substitutions causing a structurally abnormal globin and may be either congenital or acquired. Acquired forms of hemoglobinopathies include the following: methemoglobin, sulfhemoglobin, and carboxyhemoglobin.
True or False
true
Hemoglobinopathies are due to amino acid substitutions causing a structurally abnormal globin (e.g. HbS, HbE, HbC, HbG-Philadelphia, HbD, HbO-Arabia. Interactions among thalassemias and hemoglobinopathies are common (e.g. HbS and HbC). Some congenital hemoglobinopathies are characterized by an altered affinity for oxygen (e.g. M Hb). Acquired hemoglobinopathies associated with altered affinity for oxygen include methemoglobin, sulfhemoglobin, and carboxyhemoglobin.
The most common enzymatic defect of the red blood cell associated with hemolysis is G6PD deficiency.
True or False
true
G6PD deficiency is the most common enzymatic defect. G6PD deficient RBCs cannot generate adequate NADPH and reduced glutathione and are sensitive to oxidative stress resulting in hemolysis and bite cell formation. The hemolytic episode is commonly triggered by medications or fava bean ingestion. The diagnosis is made by measuring G6PD enzyme levels after cessation of an acute hemolytic episode, since reticulocytes have a higher enzyme level and reticulocytosis (a characteristic of hemolysis) may confound the diagnosis. Treatment for G6PD is the avoidance of precipitating causes. The second most common enzyme deficiency associated with hemolysis is Pyruvate Kinase (PK) deficiency.
