Blood Disorders Flashcards

Question

Ehlers Danlos Syndrome

Answer 1

Autsomal Dominant Six types-Type IV is vascular type Mutation in COL3A1 gene (heterogenous) Leads to think skin, arterial or uterine rupture, small joint hyperextensiblity Gene Abnormalities affect overall synthesis, secretion and synthesizing abnormal collagen III Rupture of large arteries and colon common

Answer 2

Point mutation in B-globin that promotes the polymerization of deoxygenated hemoglobin, leading to red cell distortion, hemolytic anemia and microvascular obstruction B-glboin point mutation from glutamic acid to valine (hydrophobic interaction among Hg molecules) Protects agains falciparum malaria-infected cells increase sickling and get phagocytosed Pathogenesis HbS molecules stack into polymers when deoxygenated creating a viscous gel HbF inhibits polymerization of HbS (infants not symptomatic) Intracellular pH decrease reduces the oxygen affinity increasing the number of deoxygenated HbS and sickling occurs transit time in spleen, bone marrow and inflamed vascular beds is slow making them more prone to sickling and occlusion HbS polymers project from cell cuasing influx of Ca2+ which induces cross linking of membrane porotiesn and activates ion channels causing efflux of K+ and H2O leading to sickling and extravascular hemolysis Morphology: peripheral blood has sickled cells, reticulocytosis and target cells Howell Jolly bodies (small nuclear remnants) present in red cells due to asplenia Bone Marrow hyperplastic for compensation leading to bone resorption and secondary formation resulting in prominent cheekbones and changes in skull (crewcut appearance) Extramedullary hematopoiesis can appear Increased breakdown of RBCs leads to gallstones and hyperbilirubinemia Splenomegaly in early child progresses to autosplenectomy Spleen will appear brown, shrunken and fibrotic after vasocclusive crises Vascular stagnation causes leg ulcers Clinical: hemolyic anemia punctuated by crises vaso-occlusive or pain crises of hypoxic injury commonly in bones, lungs, liver, brain, spleen and penis (erectile dysfunction) Dactylitis of hands and feet Acute chest syndrome (most common form of death-vasocclussive crisis in pulmonary vasculature), avascular necrosis, stroke and blindness can occur Aplastic crises due to parvovirus B19 Impairment of growth, increased susceptibility to infections with encapsulated organisms Renal papillary necrosis-microhematuria Salmonella osteomyelitis (Vi Ag prevents phagocytosis) Diagnosis: clinical, sickled cells, mixing blood sample with oxygen consuming agent (metabisulfite) induces sickling, electrophoresis demonstrates presence of HbS Increased indirect bilirubin, increased LDH, decreased haptoglobin Treatment: inhibitor of DNA synthesis increases red cell HbF levels (hydroxyurea), anti-inflammatory effects-inhibition of leukocyte production Gardos channel blockers

Answer 3

Acquired mutations in the phosphatidyliniositol glycan complementation group A (PIGA) gene an enzyme essential for synthesis of membrane associated complement regulatory proteins PIGA is X linked and susceptible to acquired mutations and inactivation leading to less proteins bound to phospholipid bilayer by glycosylphosphatidylinisoitol (GPI) Causative mutations in Hematopoietic stem cells so RBCs, WBCs, and platelets all affected CD59 most important proteins affected (inhibitor of C3 convertase) RBCs lacking GPI linking factors (for decay accelerating factor) susceptible to lysis or injury by complement leading to intravascular hemolysis by MAC Can lead to iron deficiency Triad of -Coombs test hemolysis, pancytopenia and Thrombosis (hypercoagulability) is leading cause of death mostly venous thrombosis Dark urine in morning Diagnosed by flow cytometry detecting Red cells deficient in GPI linked proteins such as CD59 and CD55 Treatment: eculizumab prevents conversion of C5 to C5a and lowers risk of thrombosis (high cost and increase risk of fatal meningococcal infections) HSC transplantation

Answer 4

Asymptomatic condition in which individuals are heterozygous for HbS

Answer 5

symptomatic sickling disorder caused by HbC increasing HbS tendency to polymerize (lose salt and water and become dehydrated)

Answer 6

Hemolytic anemia caused by Abs that bind to red cells leading to their premature destruction Diagnosis: by direct Coombs antiglobulin test or indirect Coombs antiglobulin test Most common form of immunohemolytic anemia Most commonly IgG Mostly extravascular IgG coated red cells bind to Fc receptors on phagocytes which remove red cell membrane during partial phagocytosis leads to spherocytes which are destroyed by spleen Moderate splenomegaly is seen Antigenic drug induced immunohemolytic anemia follows large IV drug doses occurring 1-2 weeks after therapy is initiated tolerance breaking drugs induced immunohemolytic anemia (methyldopa) induce Abs against Red cell Ags in Rh blood group Also called autoimmune hemolytic anemia due to being assoiciated with SLE, CLL or drugs-a methyldopa treatment: remove drug, immunosuppressive therapy and splenectomy

Answer 7

Hemolytic anemia caused by Abs that bind to red cells leading to their premature destruction Diagnosis: by direct Coombs antiglobulin test or indirect Coombs antiglobulin test Caused by IgM Abs that bind red cells at low temps Occur after infections with mycoplasma pneumonia, EBV, cytomegalovirus, influenza, and HIV-self limited though Chronic cold agglutinin associated with B cell neoplasms,CLL Clinically in cold areas of body:fingers toes and ears Red cells agglutinate and fix complement rapidly leading to opsonization within spleen, liver and bone marrow Vascular obstruction causes pallor, cyanosis and raynaud phenomenom in cold body parts treatment: remove drug, immunosuppressive therapy and splenectomy

Answer 8

Single nucleotide mutation-glutamine to arginine substitution Factor V becomes resistant to cleavage and inactivation by protein C (hypercoagluability) Recurrent DVT prominent association, cerebral vein thrombosis, and recurrent pregnancy loss

Answer 9

intrinsic hemolytic normocytic anemia Abnormalities in hexose monophosphate shunt or glutathione metabolism resulting from deficient enzyme function reducing the ability of red cells to protect themselves against oxidative injuries leading to hemolysis G6PD reduces NADP to NADPH while oxidizing glucose-6-phosphate NADPH converts oxidized glutathione to reduced glutathione protecting against oxidant injury X linked recessive trait (africans, asisans, mediterranean) Associated with hemolysis due to misfolding of a protein-older cells more susceptible Protective against malaria falciparum Episodic (intravascular and extravascular) hemolysis caused by exposures that generate oxidant stress ( sulfa drugs, antimalarials infections, and fava beans) Back pain and hemoglobinuria (purple urine) after stress Oxidant stress causes sulfhydryl groups on globin chains to denature becoming Heinz bodies (cause intravascular hemolysis and bite cells) Recovering phase characterized by reticulocytosis

Answer 10

Abnormally high red cell coutn usually corresponding to increases in hemoglobin level Relative polycythemia: dehydration or stress characterized by hypertension, obesity, and anxiousness Absolute polycythemia: primary due to intrinsic abnormality in hematopoietic precursors Secondary: when RBCs responding to increased erythropoietin Most common cause is polycythemia vera a myeloproliferative disorder associated with mutations leading to erythropoietin-independent growth of red cell progenitors Congenital Causes: inherited Erythropoietin receptor mutations, defects that stabilize HIF-1a affinity (chuvash polycythemia, prolyl hydroxylase mutations) Acquired- Primary: Polycythemia Vera Secondary: Lung Disease, high altitude living, cyanotic heart disease, paraneoplastic

Answer 11

Exposure to A or B like Ags in food, bacteria, viruses or just naturally occurring IgG (normally IgM Ab) to A or B Ag crosses placenta Leading to hemolysis in newborn with Ag to IgG Ab Jaundice in first day of life Can occur in first pregnancy

Answer 12

Rh- mother exposed to RH+ blood of fetus during delivery Develops Anti-Rh IgG Subsequent pregnancies anti Rh IgG crosses placenta leading to hemolytic disease of the newborn Erythroblastosis fetalis: anemia, jaundice, edema (hypoxic liver and cardiac injury) Nucleated erythrocytes and persistent extramedullary hematopoiesis

Answer 13

Lead inhibits ferrochelatase and ALA dehydratase leading to decreased heme synthesis and increased RBC protoporphyrin (lead has strong affinity for sulfydryl groups leading to inhibition) However D-aminolevulinic acid can be formed via succinyl CoA and glycine using pyridoxal phosphate (D ALA increased in urine and blood during poisoning) Lead inhibits rRNA degradation (basophlilic stippling) High risk in old houses with chipped pain, soil, pottery, moonshine Symptoms: weakness, abdominal pain, constipation, lead lines on gingiviae and metaphyses of long bones on X-Ray Encephalopathy and Erythrocyte basophilic sippling, wrist and foot drops Sideroblastic anemia Treat with Dimercaprol and EDTA 1st Succimer chelation for kids

Answer 14

Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) defect in UMP synthase (orotate phosphoribosyl transferase and OMP decarboxylase which catalyze oratate to UMP) AR Children present with megaoblastic anemia that cannot be cured with folate or B12 with failure to thrive No hyperammonemia (vs ornithine transcarbamylase deficiency) Hypersegmented neutrophils, glossitis, orotic acid in urine Treatment: uridine monophosphate (inhibits carbomoyl phosphate synthetase II leading to attenuated orotic acid production) to bypass mutated enzyme

Answer 15

decreased hpatoglobin, increased LDH, schistocytes and Increased reticulocytes on peripheral blood smear Urobilonogen in urine Causes: paroxysmal nocturnal hemoglobinuria, mechanical destruction, microangiopathic hemolytic anemias

Answer 16

Macrophage in spleen clears RBC Spheocytes in peripheral smear Increasd LDH plus increased unconjugated bilirubin which leads to jaundice

Answer 17

AR Intrinsic hemolytic normcytic anemia Extravascular Defect in pyruvate kinase leads to decreased ATP which leads to rigid RBCs Hemolytic anemia in a newborn

Answer 18

May still have renal papillary necrosis and microhematuria Limited ability to concentrate urine Normal peripheral smears (no sickle cells, normal reticulotytes and MCHC) Will still sickle when exposed to sodium metabisulfite

Answer 19

Decreased ability to inactivate factors V and VIII Increased risk of thromobotic skin necrosis with hemorrhage following warfarin administration (hypercoagulable state)

Answer 20

Acute inflammatory response to infection Increase WBC count and Increase neutrophils and neutrophil precursors-band cells increased leukocyte ALP (not in CML)

Answer 21

Decreased plasma volume Normal RBC Mass Normal O2 saturation Normal EPO levels Decreased plasma volume (dehydration, burns, diuertics)

Answer 22

Normal Plasma volume increased RBC mass Decreased O2 saturation Increased EPO levels Lung disease, congenital heart disease, high altitude

Answer 23

Normal plasma volume Increased RBC mass Normal O2 saturation Increased EPO levels RCC, Wilms tumor, cyst, HCC, hydronephrosis Ectopic EPO