Red Blood disorders Flashcards
(135 cards)
1
Q
Anemia
A
Decreased in RBC mass
2
Q
Anemia
A
Decreased in RBC mass
3
Q
Anemia in males vs females
A
Males
4
Q
Microcytic anemia
A
MCV
5
Q
Heme
A
Iron and protoporphyrin
6
Q
Hemoglobin made of
A
Hene and globin
7
Q
Microcytic anemia caused by deficiencies in what 4 things
A
Heme, globin, iron, protoporphyrin (sideroblastic anemia)
8
Q
What are the 4 microcytic anemias
A
Iron deficiency anemia
Anemia of chronic dz
Sideroblastic anemia
Thalassemia
9
Q
Anemia in males vs females
A
10
Q
Microcytic anemia
A
MCV
11
Q
Heme
A
Iron and protoporphyrin
12
Q
Hemoglobin made of
A
Hene and globin
13
Q
Microcytic anemia caused by deficiencies in what 4 things
A
Heme, globin, iron, protoporphyrin (sideroblastic anemia)
14
Q
What are the 4 microcytic anemias
A
Iron deficiency anemia
Anemia of chronic dz
Sideroblastic anemia
Thalassemia
15
Q
Iron deficiency anemia
A
Decreased iron = decreased heme = decreased Hb = microcytic anemia
16
Q
How is iron absorbed
A
Heme/non-heme forms
Duodenum
Enterocytes have DMT1 transporters
(heme form more readily absorbed) and transport iron across cell membrane into blood via ferroportin
Transferrin stores iron in blood & delivers it to liver & bone marrow macrophages for storage
Stored intracellularly bound to ferritin
17
Q
Lab iron status measurements
A
Serum iron
TIBC
% saturation
Serum ferritin
18
Q
Iron in body
A
Iron in blood bound to transferrin
Every 3 transferrin - 1 will be carrying iron
In macrophages iron bound to ferritin
19
Q
Serum iron
A
Iron in blood
20
Q
Transferrin molecules
A
TIBC - total iron binding capacity
21
Q
% saturation
A
How many transferring bound to iron
22
Q
Serum ferritin
A
How much iron present in liver and bone marrow macrophages
23
Q
Dietary deficiency or blood loss
A
Breast feeding infants
Poor diet in children
Adults: PUD - males, pregnancy/menorrhagia (females)
Elderly - Western world - colon polyps, carcinoma vs developing world - hook worm (necator and ancylostoma)
24
Q
Other causes of iron deficiency
A
malnutrition
malabsorption (acid aids in iron absorption)
gastrectomy
25
Fe2+ or Fe3+ absorbed by body?
Fe2+ goes into the body and acid keeps it the Fe2+ state.
26
Stages of iron deficiency
Storage iron depleted (ferritin) - TIBC will go up
Serum iron depleted
Normocytic anemia
Microcytic, hypochromic anemia
27
If ferritin is down - liver and macrophages will pump out more transferring molecules out to find iron
Ferritin down
| TIBC will go up
28
What type of anemia is in the very early stage of iron deficiency?
Normocytic anemia
29
Lab findings of microcytic anemia
MCV
30
Tx of microcytic anemia
ferrous sulfate
31
Plummer-Vinson syndrome
Iron deficiency anemia with esophageal web/atrophic glossitis
Anemia, dysphagia, beefy-red tongue
32
Anemia of chronic disease
Chronic inflammation/cancer
Most common anemia in hospitalized patients
33
ACD anemia
increase in acute phase reactants - Hepcidin which locks iron in storage sites so it can't be used
Limits iron transfer from macrophages to erythroid precursors
Hepcidin Suppresses EPO production
34
Lab findings in ACD
Increases ferritin, Decreased TIBC
Decreased serum, decreased % saturation
Increased FEP (not a problem with protoporphyrin)
35
Tx of ACD
Addressing underlying cause
| Exogenous epo - especially cancer patients
36
Sideroblastic anemia due to
defective protoporphyrin synthesis - resulting in low heme - low Hb - microcytic anemia
37
Protoporphyrin synthesized via series of reactions
Final reaction attaches protoprphyrin to iron to make heme (7-8 reactions)
(ferrochelotase)
*Occurs in mitochondria
38
Steps of protoporphyrin production
```
Succinyl CoA converted to aminolevulinic acid by Aminolevulinic acid synthetase
S CoA (ALAS) ALA (rate limiting step) - VIT B6 is cofactor
```
ALA to prophobilinogen by Aminolevulinic acid dehydrogenase
ALA (ALAD) Prophobilinogen
Final reaction - protoporphyrin + iron = heme by ferrocheletase in mitochondria
39
Iron transferred to precursor
Iron from bone marrow macrophages to erythoblasts - iron and protoporphyin meet in macrophage to make heme
40
What happens if protoporphyrin is deficient?
Iron gets trapped in mitochondria
| Iron laden mitochondria form ring around nucleus of erythroid precursors - cells called sideroblasts
41
What stain marks iron?
prussian blue stain
42
What enzyme is involved most commonly in congenital sideroblastic anemia?
ALAS (rate limiting enzyme)
43
Common causes of acquired sideroblastic anemia?
```
Alcoholism (mito poisoning)
Lead poisoning (LAD/ferrochelatase)
Vit B6 deficiency (for ALAS) - common in isoniazid deficiency
```
44
Lab findings in sideroblastic anemia
Iron overloaded state
increased ferritin, decreased TIBC
Increased serum iron, increased % saturation
Iron - damages cells/death by free radicals - so iron leaks out and bone marrow eats iron, some can leak into blood
45
Thalassemia
decreased synthesis of globin chains - decreasing Hb
Thalasemmia is decrease in synthesis!
Inherited mutation
46
What kind of malaria are people with thalassemia protected against?
Plasmodium falciparum malaria
47
What are the three normal types of Hb?
HbF (alpha2,gamma2)
HbA (alpha2,beta2)
HbA2 (alpha2,delta2)
alpha common - most important in all globin chains
48
How many copies of alpha allele?
4 on chromosome 16
49
Alpha thalassemia - is due to
Gene deletion
50
What happens when one alpha is deleted?
Asymptomatic
51
What happens when 2 alpha genes are deleted?
Mild anemia with slightly increased RBC count
52
What are the possibilities for 2 alpha gene deletions
Cis - worse than trans - increased risk of severe thalassemia in offspring (seen in Asians)
Trans - one deletion of gene on each chromosome (Africa)
53
What about when 3 alpha genes are deleted?
Severe anemia
| Beta chains form tetramers (HbH) that damage RBCs
54
What is HbH
beta chain tetramer
55
What happens when 4 alpha genes deleted?
Lethal in utero - hydrops fetalis
Gamma chains form tetramers (Hb Barts) that damage RBCs
Hb Barts seen on electrophoresis
56
Beta thalassemia due to
Gene mutations
2 genes present on chromosome 11
Mutations in absent (Betanull) or diminished (Beta+) production of beta globin chain
57
Mildest form of beta thalassemia
B/B+
Beta thalassemia minor
Usually asymptomatic with increased RBC count
Microcytic, hypochromic RBCs and target cells on smear
Increased HbA2
58
Target cell
decreased cytoplasm or increased membrane
59
Most severe form of beta thalassemia
Beta(null)/Beta(null) - beta thalassemia major
Severe anemia few months after birth
HbF (alpha2gamma2) at birth is temporarily protective
form alpha tetramers that damage RBC - ineffective erythropoiesis/extravascular hemolysis
60
Beta thalassemia - massive erythroid hyperplasia
Expansion of hematopoeisis into marrow of skull/facial bones
(EPO released by kidney) - skull - crew cut appearnace on x-ray, facial bones thickened "chipmunk like face"
Extramedullary hematopoiesis with HSM
Risk of aplastic crisis with parvovirus B19
61
Tx for beta thalassemia
Chronic transfusion
At risk for secondary hemochromatosis
62
Beta thalassemia blood smear
Microcytis, hypochromic target cells, nucleated RBC
63
Beta thalassemia
No HbA
Increased HbA2 and HbF
64
Macrocytic anemia
MCV>100
larger than normal
d/t most commonly - folate/VitB12 deficiency
one less division than normal (DNA precursor deficiency)
65
THF
comes in and quickly gets mehtylated - VIT B12 takes methyl group
VIT B12 passes methyl group to homocysteine and becomes methionine - transfers methyl groups
66
Lack of VIT B12 or folate
```
Megaloblastic anemia
Hypersegmented neutrophils (greater than 5 lobes)
Megaloblastic change in all rapidly dividing epithelial cells
```
67
Other causes of macrocytic anemia
Alcoholism
Liver dz
Drugs (5-FU)
68
Where is folate absorbed?
Jejunum
69
Folate deficiency
```
poor diet (minimal stores) - alcoholics, elderly
Increased demand (pregnancy, cancer, hemolytic anemia)
Folate antagonists (MTX)
```
70
Lab findings of macrocytic anemia
```
Macrocytic RBC and hypersegmented neutrophils
Glossitis
Decreased serum folate
Increased serum homocysteine
Normal methylmalonic acid
```
71
B12
complexed to animal derived proteins
Cleaved then bound to R-binder from salivary gland
Then goes to small bowel - R binder cleaved by pancreatic proteases
VITB12 bound by IF (parietal cells of stomach) and absorbed by ileum
72
Most common cause of B12 deficiency
AI destruction of parietal cells leading to intrinsic factor deficiency
73
Parietal cell
proton pumps
pink - upon staining
Pernicious anemia
"P"
74
Other causes of VIT B12 deficiency
```
Pancreatic insufficiency (can't cleave from R-binder)
Damage to terminal ileum d/t Chron's dz or diphyllobthrium latum
Dietary deficiency (rare execpt in vegans)
```
75
Clincal findngs B12 deficiency
Macrocytic anemia with hypersegmented neutrophils
Glossitis
Subacute combinded degeneration of spinal cord (from methylmalonic acid building up - can't be converted to succinyl-CoA - builds up in myelin)
76
Lab findings in B12 deficiency anemia
Decreased serum vit B12
Increased serum homocysteine
Increased methylmalonic acid (can't be converted to succinyl CoA)
77
Normocytic anemia definition/cause
RBC are normal size but decreased amount
d/t peripheral destruction or underproduction
78
How do you determine normocytic anemia is peripheral destruction or underproduction
Reticulocyte count - young RBC from bone marrow
Bluish cytoplasm from residual RNA
79
Reticulocyte count falsely elevated in
macrocytic anemia
Decreased in total RBC falsely elevated % reticulocytes
80
Corrected reticulocyte count
Multiply reticulocyte count by Hct/45
>3% = good marrow response and suggests peripheral destruction
81
Extravascular hemolysis invovles RBC destruction by
RE system: macrophages of spleen, liver, lymph nodes - break down Hb
82
Break down of Hb
Globin - amino acids
Heme - iron and protoporphyrin
Protoporphyrin - unconjugated bilirubin
83
Clinical findings of extravascular hemolysis
Anemia with splenomegaly
Jaundice - unconjugated bilirubin
Increased risk for bilirubin gallstones
Marrow hyperplasia w/ corrected reticulocyte count >3%
84
Intravascular hemolysis and findings
Hb binds haptoglobin - (complex) - so free haptoglobin levels decrease
Hemoglobinemia
Hemoglobinuria
Hemosiderinuria
Decreased serum haptoglobin
85
Normocytic anemia with predominant extravascular hemolysis
Hereditary spherocytosis
Sickle cell anemia
Hemoglobin C
86
Hereditary spherocytosis
Inherited defect in RBC cytoskeleton membrane tethering proteins
*ankryin, spectrin, band 3.1
Membrane blebs formed and lost over time - so cells round
87
Spherocytes less able to maneuver thru
splenic sinuses so they're consumed
88
Clinical and lab findings hereditary spherocytosis
Spherocytes w/ loss of central pallor
Increased RDW
Increased MCHC
Splenomegaly, jaudice w/ unconjugated bilirubin - increased risk for bilirubin gallstones
Increased risk for aplastic crisis (parvo B19) - erythroid precursor
89
Dx of hereditary spherocytosis
osmotic fragility test: increased spherocyte fragility in hypotonic soln
90
Tx of hereditary spherocytosis
Splenectomy - anemia resolves but spherocytes persist
Howell Jolly bodies
91
Sickle Cell anemia
AR mutation in Beta chain in hemoglobin
Glutamic acid (hydrophilic) replaced with valine (hydrophobic)
92
What malaria is protected against in SCD?
Falciparum malaria
93
Sickle cell dz vs trait
SCD:
2 abnormal beta genes present
>90% HbS in RBC
SCT:
one mutated and one normal beta chain
94
HbS polymerizes when
deoxygenated
Aggregates into needle like structures resulting in Sickle cells
(hypoxemia, dehydrogration, acidosis)
95
Protective factor against sickling
HbF
| Tx: hydroxyurea increases levels of HbF
96
Extravascular hemolysis symptoms SCD
Anemia
Jaundice with unconjugated hyperbilirubinemia
Increased risk for bilirubin gallstones
97
Intravascular hemolysis with SCD
decreased haptoglobin
Target cells on blood smear
98
SCD - massive erythroid hyperplasia
Expansion of hematopoiesis into skull/facial bones
Extramedullary hematopoiesis with hepatomegaly
Aplastic anemia crisis (Parvo B19)
99
Dactylitis
Common in infants
| Swollen hands/feet d/t vao-occlusive infarct of bone (irreversible sickling)
100
Autosplenectomy
Irreversible sickling
Increased risk of infection with encapsulated organisms (most common cause of death in children)
Increased risk of salmonella osteomyelitis
Howell Jolly bodies
101
What is the most common cause of death in children w/ SCD?
Encapsulated organsims
102
Acute chest syndrome
Vaso-occlusive in pulm microcirculation
Chest pain, SOB, lung infiltrates, often precipitated by pneumonia
Most common cause od death in adults (SCD)
103
Most common cause of death in adults w/ SCD?
Acute chest syndrome
104
Pain crisis in SCD
vaso-occlusion crisis
105
Renal papillary necrosis
Gross hematuria and proteinuria
Vaso-occlusive crisis
106
Sickle cell trait
One normal beta gene
One mutated beta gene
HbA and HbS
More HbA than HbS
50% S to sickle so these patients asymptomatic
107
Sickle cell trait doesn't sickle except for...
Renal medulla
Extreme hypoxia and hypertonicity cause sickling
Microinfarctions that lead to microscopic hematuria and decreased ability to conc urine
108
Sickle cell trait
Metabisulfite screen: causes HbS to sickle
No sickle cell dz or target cells
109
HbC
Ar - Beta chain
Glutamic acid replaced by lysine
Less common than SCD
Mild anemia d/t extravascular hemolysis
HbC crystals
110
Normocytic anemia with predominant intravascular hemolysis
Paroxysmal nocturnal hemoglobinuria (PNH)
G6PD deficiency
Immune Hemolytic anemia
Microangiopathic hemolytic anemia
Malaria
111
Paroxysmal nocturnal hemoglobinuria (PNH)
DAF on surface
MIRL on surface
by GPI anchoring protein in normal cells *acquired defect in myeloid stem cell so GPI not present
In PNH - no GPI so no DAF/MIRL so susceptible to complement (intravascular hemolysis at night)
Retain carbon dioxide causing acidosis activating complement when we sleep
Dark urine in morning
112
Intravascular hemolysis - PNH
Hemoglobinermia
Hemoglobinuria
Hemosiderinuria seen days after hemolysis
113
Screen for PNH
Sucrose test
Confirmatory test: acidified serum test of flow cytometry to detect lack of CD55 (DAF)
114
Most common cause of death in PNH
Thrombosis
Platelet fragments activated coagulation cascade - hepatic, portal, cerebral veins
115
Complications of PHN
Iron deficiency Anemia
| Myeloid stem cell mutation - can result in AML
116
G6PD deficiency
X linked R
Cells susceptible to oxidative stress (glutathione antioxidant neutralizes H2O2 + GSH - GS-SG) - needs to get back to GSH by NADPH which is produced by G6PD
If no G6PH - don't make reduced glutathione so increased oxidative stress to red blood cells
117
2 major variants G6PD variants
African - mildly reduced half like g6pD
Mediterranean variant - markedly reduced half life G6PD
118
G6PD deficiency protective against
Falciparum malaria
119
What are the oxidative stress inducers of Heinz bodies
Infections, drugs, (primaquine, sulfa drugs, dapsone, fava beans)
120
Screen for G6PD deficiency
Heinz prep - do this after resolved acute hemolytic episode resolved
121
What mediates extravascular hemolysis
| Immune mediated anemia
Immune mediated anemia
IgG (extravascular hemolysis - warm) or IgM (intravascular - cold)
Results in spherocytes
122
Immune mediated anemia associated with
SLE, CLL,certain drugs
123
TX: immune mediated anemia
Cessation of offending drug
IVIG
Steroid
Splenectomy
124
IgM mediated intravascular hemolysis (immune mediated anemia) associated with what to infections
Mycoplasma pneumoniae
| Infectious mono
125
What test to dx IHA
Direct/Indirect coombs test
Direct: do I have RBC already bound by IgG - anti IgG added
Indirect: Does pt have antibodies in the serum?
126
Microangiopathic hemolytic anemia
Intravascular hemolysis from vascular pathology
Iron deficiency anemia occurs with chronic hemolysis
Occurs with mircothrombi: TTP-HUS, DIC, HELLP
microthrombi, prosthetic heart valves, aortic stenosis (calcified valves crushes RBC)
127
Malaria causes hemolysis
Transmitted by Anopheles mosquito
Infection of RBCs and liver plasmodium
128
RBC ruptures as part of plasmodium life cycle
Intravascular hemolysis and cyclical fever
129
Fever cycle P falciuparum
daily
130
Fever cycle P vivax and ovale
Fever every other day
131
Anemia d/t underproduction
Decreased production of RBC by bone marrow
Low corrected RC
Microcytic and marcocytic anemia
Renal failure
Damage to bone marrow precursor cells
132
Parvo virus
Temporary halts erythropoiesis
Significant anemia in preexisting marrow stress
Tx; supportive
133
Aplastic anemia
Damage to HSC
Pancytopenia w/ low RC
Drugs/chemicals, viral, AI damage
Biopsy reveals empty, fatty marrow
134
TX aplastic anemia
```
Cessation of causative drugs
Transfusions
Marrow stimulating factors (EPO, GM-CST, G-CSF)
Immunosuppression
BMT (last resport)
```
135
Myelophthisic process
pathologic process replaces bone marrow
Pancytopenia
