2/15 - Erythrocyte Enzyme Deficiencies & Hereditary Spherocytosis And Pathology Of Anemia

Front 1

Anemai with elevated reticulocytes tell you that the problem does not stem from the ____

Back 1

bone marrow

(bone marrow is normally producing RBC @ ^ rate but somethings is destroying the RBCs)

Front 2

Evidence of hemolysis

Back 2

Jaundice (skin & sclera)

Pallor (bc anemic)

Dark urine (Hb & hemosiderin in urine)

^ Reticulocytes

^ LDH (enzyme present in RBCs)

^ indirect/unconjugated bilirubin (bc ^ breakdown of heme, liver is overwhelmed)

Front 3

Name the 4 morphological hallmarks of Hemolysis

Back 3

1)Polychromasia - immature cell showing tha tBM is working harder; larger than RBC & bluish in color

2)Spherocytes - more round (not biconcave), more Hb crammed into a small space -> darker appearance; classic for autoimmune hemolytic anemia & hereditary spherocytosis

3)Schistocyte - fragmented cells that are ripped apart in circulation; fibrin deposition in small BV, sharp edges; seen in microangiopathic hemolytic anemias, heart valves, DIC

4)Nucleated RBC - easily recognizable; suggests that BM is working hard

Front 4

RBC sole source of energy?

Back 4

Glycolysis - remember RBC lack mitochondrea

also NO NUCLEUS or RIBOSOMES - do not make protein, just carry O2 and Hb

Front 5

What does RBC need ATP for (6)?

Back 5

1) Na/K pumps
2) Ca pumps
3) Needs energy to maintain biconcave disc shape
4)Regulation of phospholipid in bilipid membrane so that negative are insede and positive outside (prevents coagulation)
5)Reducing equivalents - keep reduced glutathione to prevent oxygen damage
6)Keep sulfhydryl groups present (maintain ferrous form)

Front 6

Through what biochemical pathway does RBC get its reducing equivalents (GSH)?

Back 6

Hexose monophosphate shunt

10% of glucose goes through (90% through glycolysis)

Front 7

Key enzyme in Hexose monophosphate shunt?

Back 7

Glucose-6-phosphate dehydrogenase (G6PD)

G6PD converts NADP+->NADPH; Glutathione reductase then uses this NADPH to make glutathione

ABSOLUTELY have to have this and Hexose monophosphate shunt to keep RBC healthy

Front 8

T/F G6PD Deficiency is mostly suffered by men?

T/F G6PD Deficiency is a chronic hemolytic anemia?

Back 8

T, X-linked dz

F, just episodic hemolysis..there is a Shortened RCB survival, in general affected people have a normal Hb and normal life

Front 9

G6PD Def can cause what in neonatal period?

Back 9

Common cuse of neonatal Kernicterus and Jaundice (lead to mental retardation)

Front 10

T/F Old cells have more G6PD than young cells?

Back 10

**F, young cells usualy have more G6PD ("important test point")**

degree of deficiency of old cells PREDICTS the severity of anemia

Front 11

Describe the mechanism of hemolysis by G6PD Def

Back 11

Oxidants can damage any protein with sulfhydryl group, particularly Hb b/c it ahs oxygen & is easily damaged when not much glutathione around

Denatured, oxidized Hb can precipitate and form HEINZ BODIES

Front 12

Heinz bodies affects of RBC (2)?

Back 12

1) very toxic to cell; adhere to RBC membreane making it stiffer and more difficult to transverse microcirculation and spleen

2)easily lysed -> v RBC survival (frank hemolysis)

Front 13

T/F Neonatal jaundic enot actually a hemolytic problem?

Back 13

T, G6PD Def comvined iwth Gilbert's disease (deficiency of bilirubin conjugation enzyme) can result in very high bilirubin levels and may -> kernicterus -> mental retardation

Front 14

Phagocytosed Heinz bodies called?

Back 14

Bite cells, usually formed in spleen

Both 1)Bite Cells & 2)Heinz bodies used for diagnosis of G6PD deficiency

Front 15

T/F ther is no clinical significance wtih G6PD A+

Back 15

T, normal G6PD activity, just migrates differently on electrophoresis gel

Front 16

Normal type of G6PD is?

Back 16

G6PD B (bulk of world's population

Front 17

MC form of G6PDD in america

Back 17

G6PD A-

Moderate to severe hemolysis w/ stress

Cells decay faster so there are more cells w/ v G6PD

Esp larger % in blackies ;)

Front 18

One benefit seen by ALL G6PD genetic defects?

Back 18

Malaria resistance

Front 19

Southeast Asian form of G6PD defect?

Back 19

G6PD Canton

Front 20

More severe type of G6PD defect?

Back 20

G6PD B-

Sever hemolysis after stress

Lower activity level, decays even faster (bc less cellular protective effects)

Can be associate with favism (damn you fava beans!!)

Front 21

Give some examples of oxidant drugs

Back 21

Antimalarias - primaquin, chlorquin

Sulfa drugs - sulfonylamide

Nitrofurantoin


All make you esp vulnerable when suffering from G6PDD

Front 22

Clinical Presentation of G6PDD

Back 22

1)Acute hemolysis of oxidant stress (ie Infections, Diabetic ketoacidosis, Surgery, Oxidant drugs)

2)Appropriate ethnic or gender backgound

3)Jaundice, pallor, dark urine

Front 23

T/F Onset of G6PDD is usually gradual

Back 23

F, onset usually SUDDEN (hours to days after insult)

many times presents with BACK Pain and RETROPERITONEAL symptoms

Front 24

Something to beware when using enzyme assay to maeasure NAPDH production to test G6PDD

Back 24

NAPDH production may be NORMAL during ACUTE G6PDD episode (false negative!)

Front 25

2nd MC hemolyic RBC enzyme disorder but much less common than G6PDD? Mech?

Back 25

PK deficiency

v ATP -> cannot mantain gradients -> water loss -> cell SHRINKS and becomes RIGID

Cells cannot traverse spleen or microciculation, resulting in CHRONIC hemolysis

Front 26

Clinical Features of PK Def?

Back 26

Homozygotes are anemic and jaundiced at birth

Bc of ongoing meolysis, prone to bilirubin GALLSTONES and SPLENOMEGALY bc the spleen is full of dead and dying RBCs

usually heterozygous & heterozygots are asymptomatic

LIFELONG transfusion requirements

Front 27

Biochemical deficiency that is involved in the breakdown of RNA @ reticulocyte stage and congenital ongoing hemolysis?

Back 27

Pyrimidine 5'-nucleotidase deficiency

causes damage to RBC membrane and thus congenital ongoing hemoysis

Also seen in LEAD poisoning & THALASSEMIAS

Front 28

The process of maturation fo a mature RBC from a erythroblast takes place ____ until the reticulocyte stage, and then goes to the ____ ?

Back 28

first BM, the to peripheral blood

lose organells and nuclear material & gain Hb with RBC maturation

Front 29

How can you tell the maturity of a RBC through histology?

Back 29

by the nuclear material that it contains (the more the less mature)

Front 30

RBC takes how long for maturation?

Back 30

8-12 days

Front 31

MC form of anemia?

Back 31

Hemorrhage

Front 32

Rapid Hemorrhage defined as

Back 32

loss of more than 20% of blood volume in less than 1 hour

caused by: extravasularly by trauma & intravascularly by G6PD Def & acquired hemolytic anemia

Front 33

Patient can tolerate up to ___% loss of blood volume as long as it is not acute.

Compensatory mechs?

Back 33

70% volume tolerance by:

1)^ BP, HR, CO
2)shuntivnng of blood from peripherial system
3)increased 2,3-DPG levels

Front 34

End form of all anemias lead to?

Back 34

Tissue anoxia and/or cell death

Front 35

Describe stages of incerased RBC destruction continuum

Back 35

Anemia -> Hemoglobinuria/emia -> Jaundice (from excess Hb)-> Cholelithiasis (gall stones; trying to excrete excess bilirubin) -> Aplastic anemia -> Hemolytic crisis

Front 36

What enzyme is markedly elevaed in MEGALOBLASTIC anemia vs other types

Back 36

Serum LDH increases a lot

Front 37

Again, the 4 distinctive cell signs on blood smear indicating severe hemolysis?

Back 37

Polychormasia, Spherocytes, Schistocytes (Fragmented cells) & Nucleated RBCs

Front 38

Conplications of ^ RBC sequestration (vaso-occlusion)

Back 38

1)Autosplenectomy

2)Renal papillary necrosis - from distal capillary beds clogged

3)Dactylitis (abnormal growth of digits)

4)Sequestration crisis (v ability to oxyginate -> Acute splenic & pulmonary crisis (both often seen with Sickle Cell Dz)

5)Leg ulcers

Front 39

Abnormal growth/assymetry of digits due to the inability to oxygenate the tissues

Back 39

Dactylitis

Front 40

4 Manifestations for Erythroid Hyperplasia?

Back 40

1)Hypercellular marrow (>95% cellularity; normal cellularty for an adult is 100 minus age)

2)Extramedullary hematopoisesis (can occur in spleen, liver, etc)

3)Expansion of marrow space

4)Bone "mass' formation and deformities

Front 41

Intravascular or Extravascular hemolysis leads to what 3 things?

Back 41

1)System iron overload

2)Renal Failure

3)Liver/congestive Heart failure (tiger striping of heart due to lipid accumulation)

Front 42

A Sickle Cell Dz patient with watch will show severe cytopenia, anemia & hypocellular bone marrow with GIATN ERYTHROID PRECURSORS

Back 42

Parvo virus

Front 43

A clonal red cell abnormality that has proteins that are susceptible to complement destruction called?

Back 43

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Front 44

In Sickle Cell Dz, osteomyelitis is classically caused by what?

Back 44

Salmonella

Front 45

Bone marrow is devoid of hematopoietic elements called?

Back 45

Aplastic anemia

Front 46

Large Erythroid precursors think..

Back 46

Parvo virus

Front 47

Reticulocyte normally spends _____ in BM and _____ in peripheral blood b/f teh rest of the nuclear materials are excluded?

Difference in crisis?

Back 47

one & one

in crisis, reticulocytes shift from the BM into the blood and maturation time in blood increases to 1.5-2.5 days, depending on severity of anemia

Front 48

Reticulocyte Production Index (RPI) formula:

Back 48

RPI = (Hct/45) * Reticulocyte%/Correction factor