Chapter 5 Flashcards

Question

What are the normal types of hemoglobin?

Answer 1

HbF (a2Y2), HbA (a2b2), and HBA2 (a2delta2)

Answer 2

usually due to gene deletion; normally, 4 alpha genes are present on **chromosome 16** One gene deleted= asymptomatic Two genes deleted= mild anemia with elevaed RBC count; cis deletion is associated with an icnreased risk of severe thalassemia in offspring (seen in Asians); trans deletions seen in Africans Three genes deleted= severe anemia; B chains form tetramers (HbH) that damage RBCs; HbH seen on electrophoresis 4. Four genes deleted= lethal in utero due to hydrops fetalis; y chains form tetramers (Hb barts)

Answer 3

usually due to gene mutations (point mutations in promoter or splicing sites); seen in African and Mediterranean deescent pts. There are two B genes present on **chromosome 11** and mutations result in absent (B^o) or diminished (B⁺) production of the B-globin chain

Answer 4

Mildest form of disease and is usually asymptomatic with an increased RBC count will see microcytic, hypochromic RBCs and **target cells** on blood smear

Answer 5

slightly decreased HbA with increased HBA2 (5%, normal 2.5%) and HbF (2%, normal 1%)

Answer 6

most severe forms of disease and present with severe anemia a few months after birth there is high HbF (a2y2) at birth and is temporarily protective

Answer 7

Unpaired a chains precipitate and damage RBC membranes, resulting in ineffective eryhtrooiesis and extravascular hemolysis (removal or circulating RBCs by the spleen) Massive erythroid hyperplasia ensues resulting in expansion of hematopoiesis into the skill (resulting in **crewcut appearance-** below) and facial bones (leading to chipmunk facies), as well as extramedullary hematopoiesis wth HSM, and risk of aplastic crisis with parvovirus B19 infection

Answer 8

major tranfusions often needed leading to a risk of secondary hemochromatosis

Answer 9

HBA2 and HbF with little to no HbA

Answer 10

vitB12 or folate deficiency (megaloblastic anemia)

Answer 11

synthesis of DNA precursors- folate circulates as methyl THF and removal of the methyl roup and tranfer to vitB12 allows for participation in synthesis of DNA precursors vitB12 then transfers the methyl group to homocysteine, producing methionine

Answer 12

Impaired division and enlargemnt of RBC precursors leads to megaloblastic anemia and impaired division of grnaulocytes leads to hypersegmented neutrophils

Answer 13

Gained in diet from green veggies and fruits and absorbed in the jejunum. Folate deficiencies only take months to develop as body stores are minimal

Answer 14

poor diet (e.g. alcoholics and elderly), increased demand (e.g. pregnancy, cancer, and hemolytic anemias) and folate antagonist use (methotrextate, etc.)

Answer 15

macrocytic RBCs and hypersgemented neutrophis (5+ lobes) Glossitis decreased serum folate and increased serum homocysteiene (risk of thrombosis) normal methylmalonic acid

Answer 16

Gained in diet in animal proteins. Salivary gland enzymes such as amylase liberate vitB12 which is then bound by R-binder (also from the salivary gland) and carried through the stomach Pancreatic proteases in the duodenum detach vitB12 from R-binder and vitB12 binds to intrinsic factor from gastric parietal cells in the small bowel. The B12-IF complex is absorbed in the ileum

Answer 17

Pernicious anemia (autoimmune destruction of parietal cells) Pancreatic insufficiency and damage to the terminal ileum (Crohn disease and Diphyllobothrium latum)

Answer 18

Macrocytic RBCs with hypersgemented neutrophils Glossitis Subacute combined degeneration of the spinal cord (dorsal columns and coritcopsinal tracts) decreased serum B12 elevated homocysteine and methylmalonic acid

Answer 19

vitB12 is a cofactor for the conversion of methylmalonic acid to succinyl CoA and its deficiency results in increased levels of methelmalonic acid, which impairs spinal cord myelinization resultin in poor proprioception and vibratory sensation and spastic paresis

Answer 20

increased peripheral destruction or underproduction (reitculocyte count helps to distinguish these)

Answer 21

Young RBCs are released from the bone marrow and ID'd on a blood smear as larger cells with a bluish cytoplasm due to residual RNA NOTE: The normal reticulocyte count is 1-2% and the normal RBC life-span is 120 days and each day roughyl 1-25 are removed from circulatio and replaced by reitculocytes

Answer 22

by multiplying RC \* HCt/45 Corrected count 3+% indicated good marrow response and sugegst peripheral destruction while corrected RC of less than 3% indicates underproduction due to marrow issues

Answer 23

divided into extravascular and intravascular hemolysis- both result in anemia with an appropriate marrow response

Answer 24

This involves RBC destruction by the RES (macrophages of the spleen, liver, and lymph nodes). In this system, macrophages consume RBCs and break down hemoglobin (globin to AAs, heme to iron and protoporphyrin (iron is recycled and protoporphryin is bronw down into unconjugated bilirubin, which is bound to serum albumin and delivered to the liver for conjugation andexcretion into bile)

Answer 25

Anemia with splenomgealy, jaundice due to unconjugated bilrubin, and increased risk for bilirubin gallstones marrow hyperplasia with corrected reticulocyte count of 3+%

Answer 26

Involves destruction of RBCs within vessels with findings of hemoglobinemia, hemoglinuri, hemosiderinuria, and decreased serum haptoglobin

Answer 27

Renal tubular cells pick up some of the hemoglobin that is filtered into the urine and break it down into iron, which accumulates as hemosiderin; tubular cells are eventually shed resulting in hemosideruria

Answer 28

1) Hereditary spherocytosis 2) Sickle cell anemia 3) hemoglobin C

Answer 29

inherited defect in RBC cytoskeleton-membrane tethering proteins such as ankyrin, spectrin, or band 3. This causes membrane blebs to form and bleb over time, resulting in a round instead of disc shaped RBC and these spherocytes are les able to maneuver through splenic sinusoids and are consumed by splenic macrophages, resulting in anemia

Answer 30

Spherocytes with loss of central pallor Elevated RDW and MCHC Splenomegaly, jaundice with uncnjugated bilirubin, and risk for bilirubin gallstones Risk of aplastic crisis with parvovirus B19

Answer 31

**osmotic fragility test,** which reveals increased spherocyte fragility in hypotonic solution

Answer 32

splenectomy- anemia resolves by spheroytes persist and Howell-Jolly bodies (fragments of nuclear materal) emerge on blood smear

Answer 33

AR mutation in B chain of hemoglobin due to a single AA change from glutamic acid (hydrophilic) to valine (hydrophobic)- gene carried by 10% of AA due to malaria protection Sickle cell disease arises when two abnormal B genes are present; resulting in 90% of HbS in RBCs

Answer 34

It polymerizes when deoxygenated and the polymers aggregate into needle-like structures, resulting in sickle cells (increased sickling with hypoxemia, dehydration, and acidosis)

Answer 35

Hydroxyurea, which increases protective HbF (which is fetal and protective for the first few months of life)

Answer 36

cells continuously sickle and de-sckle passing through microciruclation reustin in complications related to RBC membrane damage including: 1. Extravascular hemolysis-RES removes RBCs with damaged mebranes, leading to anemia, jaundice with unconjugated hyperbilirubinemia, and increased risk for bilirubin gallstones 2. Intravascular hemolysis 3. Masive erythroif hyperplasia resultin expansion of hematopoiesis into the skull (crewcut) and chipmunk facies, extramedullary hematopoiesis with HSM, and risk of aplastic crisis with B19

Answer 37

1. Dactylitis- swollen hands and feet due to vaso-occlusive infarcts in bones (common presenting sign in infants) 2. Autosplenectomy- fibrotic spleen 3. Acute chest syndrome- vaso-occlusion in pulmonary microcirculation presenting with chest pain, SOB, and lung infiltrates (common cause of death in adult pts.) 4. Pain crises 5. Renal paillary necrosis-resulting in gross heamturia and proteinuria

Answer 38

Risk of infection with encapsulated organisms such as N. meningitidis, S. pneumo, and H. influenzae (most common cause of death in children) Risk of Salmonella paratyphi osteomyelitis Howell-Jolly bodies on blood smear

Answer 39

The presence of one mutated and one normal B chain resulting in less than 50% HbS in RBCs (HbA is slightly more efficiently produced than HbS) These pts are generally asymptomatic with no anemia; RBCs with less than 50% HbS do not sickle in viva except in the renal medulla due to extreme hypoxia and hypertonicity, which results in microinfarction leading to microscopic hematura and eventually decreased ability to concentrate urine

Answer 40

Sickle cells and target cells on blood smear in SCD but not in sickle cell trait Metabilsufite screen causes cells with any amount of HbS to sickle; positive in both disease and trait Hb electrophoresis confirms the presence and amount of HbS (Disease = 90% HbS, 8% HbF, 2% HbA2 (no HbA); Trait= 55% HbA, 42% HbS, 2% HbA2)

Answer 41

AR mutation in the B chain of hemoglobin where the normal glutamic acid is replaced by lysine (less common than SCD) Present with mild anemia due to extravascular hemolysis Characteristic HbC crystials in RBCs in blood smear

Answer 42

1) Paroxysmal nocturnal hemoglobinuria (PNH) 2) G6PD deficiency 3) Immune hemolytic anemia 4) Microangiopathic hemolytic anemia 5) Malaria

Answer 43

acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylionsoital (GPI) which renders cells suceptible to destruction by complement- note that red cells coexist with complement, and decay accelerating factor (DAF) on the surface of blood cells protects against complement-mediated damage by inhibiting C3 convertase. DAF is secured by GPI, an anchoring glycolipid, and the absence of GPI= absence of DAF

Answer 44

Intravascular hemolysis occurs episodically, often at night during sleep because at night mild respiratory acidosis develops with shallow breathing and activates complement, causing RBCs, WBCs, and platelets to be lysed. This intravascular hemolysis leads to hemoglobinemia and hemoglobinuria (especailly in the morning) and hemosiderinuria seen days after hemolysis.

Answer 45

Sucrose test (confirmed via the acidified serum test or flow cytometry to detect lack of CD55 (DAF) on blood cells

Answer 46

thrombosis of the hepatic, portal, or cerebral veins (destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis) complications include iron defic. anemia (due to chronic loss of hemoglobin in the urine) and acute myeloid leukemia (AML) in 10% of pts.

Answer 47

**X-linked recessive disorder** resulting in reduced half-life of G6PD, rendering cells suceptible to oxidative stresses because glutathionine normally neutralizes hydrogen peroxide, but becomes oxidized in the process, and NAPDH, a byproduct of G6PD, is needed to regenerate reduced glutathionine (this leads to intravascular hemolysis)

Answer 48

1. African variant- mildly reduced half life of g6PD leading to mild intravascular hemolysis with oxidative stress 2. Mediterranean variant marked by markedly reduced half-life of G6PD leading to severe hemolysis

Answer 49

Oxidative stress precipitates Hb as Heinz bodies (below) (especially in the setting of infections, drugs including primaquine, sulfa drugs, and dapsone, and fava beans)

Answer 50

the spleen removes them resulting in bite cells

Answer 51

IV hemolysis hemoglobinuria and back pain hours after exposure to oxidative stress

Answer 52

Heinz prep used to screen and enzyme studies to confirm

Answer 53

Antibody mediated (IgG or IgM) destruction of RBCs

Answer 54

-mainly involves extravascular hemolysis in which IgG binds RBCs in the relatively warm temps of the central body (warm agglutinin) and the membrane of these AB-bound RBCs are consumed by splenic macrophages resulting in **spherocytes**

Answer 55

SLE (most common cause), CLL, and drugs like penicillin and cephalosporins Drugs may attach to the RBC membrane with sequent binding of Ab to the complex

Answer 56

Mainly involves intravascular hemolysis in which IgM binds to RBCs and fixes complement in the relatively cold temps of the extremities RBCs inactivate complement, but the residual C3b serves as an opsonin for splenic macrophages resulting in **spherocytes**

Answer 57

M. pneumoniae and infectius mono

Answer 58

Coombs test (direct or indirect)

Answer 59

Confirms the presence of Ab or complement coated RBCs. When anti-IgG/complement is added to the pts. RBCs, agglutination occurs if RBCs are already coated with IgG or complement.

Answer 60

Anti-IgG and test RBCs are mixed with the pt. serum and agglutination occurs if serum Abs are present

Answer 61

Intravascular hemolysis that results from vascular pathology; RBCs are destroyed as they pass through the circulation Occurs with microthombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, and aortic stenosis; when presnet, microthrombi produce schistocytes on blood smear

Answer 62

Infection of RBCs and liver with Plasmodium; transmitted by the female Anopheles mosquit RBCs rupture as part of the Plasmodium life-cycle, resultin intravascular hemolysis and cyclical fever

Answer 63

P. falciparum- daily fever P. vivax and ovale- Fever every other day

Answer 64

Decreased production of RBCs by the bone marrow characterized by low corrected RC

Answer 65

1. Parvovirus B19 2. Aplastic anemia 3. Myelophthisic processes

Answer 66

It infects progenitor red cells and temporarily halts erythropoiesis leading to significant anemia tx is supportive

Answer 67

Damage to hematopoietic stem cells resulting in pancytopenia with low RC Biopsy reveals an empty, fatty marrow (below)

Answer 68

Cessation of caustive drugs and supportive care with transfusions and marro-stimulatin factors such as EPO, GM-CSF, and G-CSF Immunosuppression may be helpful as some idiopathic cases are due to abnormal T-cell activation with release of cytokines

Answer 69

Pathologic process (e.g. cancer) that replaces bone marrow resulting in pancytopenia