7. RBC Pathology Flashcards
What is a reduction of the total circulating red cell mass below normal limits, decreased O2 carrying capacity = tissue hypoxia, patients are pale, weak, and easily fatigued with malaise, mild dyspnea, dx via hematocrit (ratio of packed RBC to total blood volume) or hemoglobin?
Anemia
Microcytic normochromic = disorder of hemoglobin synthesis mostly due to iron deficieny
Normocytic normochromic = diverse things
and what is generally due to impaired maturation of RBC precursors in the bone marrow?
Macrocytic Anemia
Mean cell volume MCV= average volume of a red cell expressed in femtoliters (80-100)
Mean cell hemoglobin = avg content of hemoglobin per red cell expressed in picograms
Mean cell hemoglobin concentration MCHC= avg concentration of hemoglobin in a given volume of red cells (both two above change color of RBC)
What is the coefficient of variation of red cell volume, elevated implying the marrow is pumping out reticulocytes and is a reactive phenomenon observed in states of anemia with functioning marrow?
Red Cell Distribution Width
hematocrit / 3 = hemoglobin
Anemia is associated with paleness, weakness, malaise, easy fatigability, lowered oxygen content of the circulating blood leads to dyspnea on mild exertion DOE and or shortness of breath, chronic hypoxia may result in fatty change of the liver myocardium and?
kidney
Acute blood loss due to intravascular volume loss, if massive leads to CV collapse, shock and death, is NC/NC anemia, see decreased hematocrit and low oxygenation- EPO is released from kidneys, HCT is NOT useful during acute blood loss because is relative concentration of red cells, not the total red cell mass. reticulocytes are produced in 5 days, MCC of acute blood loss is?
Trauma
What type of blood loss shows anemia only if the rate of loss exceeds the marrow regenerative capacity or when iron reserves are depleted, male and posmenopausal women with thisv should assume to be COLON cancer until proven otherwise?
Chronic blood loss
What anemia shows red cell life span of less than 120 days, elevated EPO levels, accumulation of hemoglobin degradation products (unconjugated bilirubin), there are inc erythroid precursors in marrow d/t inc epo production, prominent reticulocytosis in PB, hemosiderosis, extramed hematopoiesis if severe and chronically may lead to elevated bilirubin in bile and pigment gallstones?
Hemolytic Anemia
Extravascular hemolysis occurs in the mo of the spleen, predisposed by RBC membrane injury, reduced deformability or opsonization, clinically see anemia, splenomegaly, jaundice, decreased haptoglobin (protein that binds to Hgb in plasma to kill RBC), usually treated by doing what?
Spleenectomy! becuase rbc damage occurs here
Intravascular hemolysis is RBC rupture due to mechanical injury, complement fixation, intracellular parasites or extracellular toxins, see anemia, hemoglobinemia, hemoglobinuria, hemosiderinuria, jaundice, NO splenomegaly, renal hemosiderosis due to iron accum, excess unconj bilirubin, free hemoglin oxidized to methemoglobin when what is deplete, which is MARKEDLY decrased in this?
Haptoglobin (low haptoglobin = hemolysis)
**MC hemolysis
What is an inherited disorder due to intrinsic defects of the red cell membrane skeleton, RBCs become spheroid, less deformable and more vulnerable to splenic sequestration and destruction, mainly extravasc hemolysis, northern europe, AD, mutation in ankyrin, band 3, band 4.2 causing reduced stability of lipid bylayer and loss of membrane fragments occurs as RBCs age- become spheroid and trapped in spleen and destroyed by mo after 10 days?
Hereditary Spherocytosis
Hereditary Spherocytosis is asso with small dark staining (hyperchromic) red cells lacking the central zone of pallor, splenomegaly and cholelithiasis in 50% of patients due to pigment stones, see inc RDW and MHCH, pt present with anemia, splenomegaly and jaundice, inc risk of asplastic crisis due to parvo19 since it stops hematopoiesis for a few weeks, low RBC levels, tx is what, which will resolve the anemia but howell jolly bodies residual RNA remain?
Splenectomy - spherocytes persist- no anemia
What is an enzyme in hexose monophosphate shunt, normally reduces NADP to NADPH, which reduces RBC glutathione and protects against oxidative stress due to fava beans, antimalaria drugs (quinidine, primaquine, chloroquine) sulfonamides, nitrofurantoins, infection inflammation?
Glucose 6 Phosphate Dehydrogenase G6PD
Glucose 6 Phosphate Dehydrogenase G6PD is prominent in AA and less severe, see episodic hemolysis due to oxidative stress, causes hemoglobin sulfhydryl crosslinking and protein denaturation, cross linking of reactive sulfhydryl groups on globin chains become denatured and form membrane bound precipitates called heinz bodies (dark inclusions visible with crystal violet)- when mo remove these inclusions they create BITE cells or become spherocytic, what is the inheritance?
X Linked Recessive
- hemolysis is greater in mediterranean variant
- anemia, hemoglobinemia, hemoglobinuria
NOTE HbA = a2b2 HbA2= a2b2 (high is B thalassemia minor/trait) HbC HbF= a2gamma2 (high HbF is B-thalassemia major) HbH= B4 HbS= a2bs2 (sickle cell trait) Hemoglobin Barts= gamma4
Usually
HbA is NL
no HbS/C/F/A2 in normal adults
at birth gamma/alpha chains are high
after birth gamma drops, beta rises, a stays high
What is hereditary hemoglobinopathy due to a point mutation which provides PROTECTION agains v. faciparum malaria, intracellular parasites consume O2, and decrease pH, promoting sickling and distorted cells and cleared more rapidly by phagocytes keeping parasite loads down?
Sickle Cell Trait (HbS/A, a2bs2)
What is hereditary hemoglobinopathy due to a point mutation in the 6th position conferring a glutamate to valine substitution in B-globin that promotes polymerization of deoxygenated hemoglobin, leading to red cell distortion, hemolytic anemia, microvascular obstruction, ischemic tissue damage, note heterozygotes are only affected in settings of profound hypoxia?
Sickle Cell Anemia/Disease (HbS/S, Bs2/Bs2)
*HbF is protective- give hydroxyurea
Sickle Cell Anemia/Disease (HbS/S, Bs2/Bs2) forms sickle shape, rate and degree depends on interactions iwht other types of hemoglobbin in the cell, HbA interferes with the polymerization of the HbS, dec MCHC levels causes a milder disease due to intracellular hydration, decreased pH increases sickling, slow transit through cap beds increases sicking- which are found most commonly in the bone marrow, inflamed tissues and?
spleen
What disease is 1 of each mutant gene, heterozygotes with RBCs that lose salt and water = dehydration, [Hb] is then increased and there is a tendency for polymerization, glutamic acid to lysine, Crystals are seen on blood smear, is a more mild than sickle cell disease?
HbSC Disease
crystalline form HbSC- symptomic compared to HbCC
Sickle Cell on peripheral blood shows sickled cells, reticulocytosis, and target cells due to RBC dehydration, along with anisocytosis and poikilocytosis, complications include autosplenectomy due to trapping of RBCs in cords and sinuses causing infarction and fibrosis, see expansion of marrow causing prominent cheekbones and changes in skull that resemble crewcut, facial bones known as?
chipmunk facies
*pigmented galllstones
Sickle Cell Anemia/Disease causes severe hemolytic anemia associted with hyperbilirubinemia, sickled cells, vasoocclusive crises are most imp complication due to episodes of hypoxic injury and infarction causing pain, no predisposing cause IDd, occurs in bones, lungs liver brain spleen penis, WHAT is MC in children and often difficult to distinguish from osteomyelitis?>
Painful Bone Crises
vasoocclusion in bones leads to swollen hands feet - **African american infants 6months = dactylitis = hand foot syndrome
Sickle Cell Anemia/Disease is assoc with what which is vaso crisis of lungs, assoc with fever cough chest pain and pulm infiltrates, MCC of death in adult pts with sickle cell anemia***, causes vasodilation, slowing blood flow which increases dehydration, acidemia, and deoxygenation creasting a cycle, may require transfusion or fatal?
Acute Chest Syndrome
Sickle Cell Anemia/Disease is assoc with priapism, sequestration crisis (death), hyposthenuria which is hypertonicity of renal medulla leading to inability to concentrate urine, stroke, retinopathy due to vascular occlusion, increased infection with encapsulated organisms, and aplastic crises with what is common where there is infection of RBC progenitor which causes a transient cessation of erythropoiesis and worsening of anemia?
Parvovirus 19*
Sickle Cell Anemia/Disease is dx based on clincal sx and labs testing of hemoglobin, metabisulfite screen +++ in both disease and trait, prenatal amniocentesis or chorionic bx, 90% live to 20, 50% to 50+, tx with hydroxyurea and HSC transplant, WHAT is the MCC of death in children with sickle cell anemia causing septicemia and meningitis, vaccinating can dec risk?
Haemophilus Influenza (has capsule!)
What is a group of disorders due to inherited mutations that decrease synthesis of either the a-globin or b-globin chains that compose adult HbA (a2b2), there are 2aglobin genes (4alleles) on chr 16, and 1b globin gene (2 alleles) on chr 11, causes anemia, tissue hypoxia, RBC hemolysis due imbalance of globin chain synthesis - anemia due to dec. RBC production and dec RBC lifespan**?
Thalassemia
What type of Thalassemia is due to dysregulation of B globin chains, see microcytic hypochromic RBCS with subnormal O2 transport capacity, RBC diminished due to imbalance of a/b globin synthesis, causes RBC microcytosis, ineffective erythropoiesis*, excessive iron absorption, anemia because HgA1 (a2b2) produced insufficiently = ineffective erythro?
B-Thalassemia
anemia is not via hemolysis
B0 Thalassemia is absent synthesis of B globin chain, MC mutation is chain terminator creating premature stop cocdons, B+Thalassemia is reduced synthesis of Bglobin chain d/t splicing mutation, without these leads to unpaire achains that precipitate in RBC precursors causing insoluble inclusions, when lack erythropoeisis see suppressed hepcidin which regulates iron, so commonly with see secondary?
hemochromatosis (inc abs iron from gut with dec hepcidin)
note: hereditary/primary you see increased ferritin which is storage form of iron*
in B-Thalassemia you see anisocytosis (variable RBC size), poikilocytosis (variable shape), hypochromic, target cells, fragmented RBCs, massive erythroid hyperplasia, iron overload with hemosiderosis and secondary hemocromatosis, affecting heart liver and pancrease, what is see which is an indicator of toxic injury to RBCs?
Basophilic Stippling
What type of B-thalassemia is asso with homozygous BThalassemia (B0B0/B+B+/B0B+), have a severe transfusion dependent anemia beginning at 6-9months, commonly in mediterranean countries,africa and SE Asia, see *HIGH HbF, see hepatosplenomegaly due to extravasc hemolysis, massive erythroid hyperplasia of skull and face, tx requires chronic transfusions - survive to 30s?
B-Thalassemia Major with HIGH HbF
What B-Thalassemia is in heterozygous alleles suchs as B+/Bwildtype or Bwildtype/B0, much more common, mild asymptomatic, microcytic hypochromic, basophilic stippling and target cells, mild erythroid hyperplasia, can be mistaken for iron deficiency anemia in pregnancy, see increased HbA2, normal HbF?
B-Thalassemia Minor/Trait
*Note: BThalassemia due to point mutations that lead to defects in transcritpion, splicing, or translation of B globin mRNA
a-Thalassemia are inherited gene deletions leading to absent or reduced synthesis of a-globin chains, infants: unpaired y-globin chains form tetramers called hemoglobin barts, Adults: unpaired B-globin for tetramers called HbH, B and Y chains are more soluble than a-globulin chains and for more stable homotetramers leadins to hemolysis and ineffective erythropoiesis which are ?
less severe than in B thalassemia
***Gene deletion is MCC of a-Thalassemia
There are 4 alleles on chr 16 for a-globin, 1 allele deleted is asymptomatic, 2 deleted is mild anemia with inc RBC count- Cis deletion = asian-symptomatic, trans deletion = african american-asx,]-> this is known as a-thalassemia trait which is clinically similar to bthalassemia minor, 3 deletions causes severe anemia = HbH tetramers, and 4 alleles deleted causes hemoglobin barts and what occurs in utero?
LETHAL in utero = hydrops fetalis
HbH disease is 3 deletions of aglobin genes, MC in asians, form tetramers of Bglobin chains called HbH, has extreme increased affinity for O2 — tissue hypoxia disproportionate to the level of Hb (not useful for O2 delivery to tissue), Hbh is prone to oxidation leading to precipitation and intracellular inclusions promoting RBC sequestration and phagocytosis in the spleen, does not require transfusion and resemble what disease?
B-Thalassemia intermedia
What occurs due to 4 mutations of aglobulin leading to tetramers of GAMMAglobin called hemoglobin barts in the fetus- greatly increased affinity for O2 causing tissue hypoxia, fetal distress during 3rd trimester, see severe pallor, generalized edema, massive hepatosplenomegaly?
Hydrops Fetalis
What is an acquired mutation of phosphatidylinositol glycan complementation group A gene PIGA, enzyme essential for synthesis of certain membrane associated complement regulatory proteins, with it absent causes cells susceptible to destruction by complement, X-linked mutation subject to lionization, it is the ONLY hemolytic anemia caused by an acquire genetic defect?
Paroxysmal Nocturnal Hemoglobinuria PNH
Paroxysmal Nocturnal Hemoglobinuria PNH is deficient in CD55 DAF, CD59 membrane inhibitor or reactive lysis, clinically RBC prone to lysis by complement caused by C5-9 MAC, 25% show paroxysmal and nocturnal- shallow nighttime breathing leads to resp acidosis and activates complement, TYPICAL is chornic hemolysis, heme iron is lost in urine, 10% develop AML or myelodysplastic syndrome, dx via flow cytometry detection of RBCs deficient in GPI linked proteins (CD59), MCC of death is WHAT?
Venous Thrombosis of hepatic, portal or cerebral veins
*tx with eculizumab (prevents C5 conversion to c5a)
What anemias are due to antibodies bound to RBCs causing their premature destruction (hemolytic/ autoimmune**), diagnosed via prsence of abs and complement on RBCs, direct coombs test: RBCs are mixed with donor serum-screen, agglutinations means pt has RBCs coated with antibodies, indirect coombs test- pt serum mixed with donor RBCs- agglutination means patient has antibodies to pts RBCs?
Immunohemolytic Anemias IHAs
