RBC Disorder Associations Flashcards
1
Q
MICROCYTIC anemia is ALWAYS due to DECREASED HGB production. What are the 4 types of MICROCYTIC anemia? What is deficient in each of these?
A
- Fe-DEFICIENCY ANEMIA - Fe
- ANEMIA OF CHRONIC DISEASE - Fe
- SIDEROBLASTIC ANEMIA - Protoporphyrin
- THALASSEMIA - Globin
2
Q
What is the most common type of anemia?
A
Fe-DEFICIENCY ANEMIA
3
Q
What is the most common cause of middle-aged MALE Fe-deficiency anemia?
A
PEPTIC ULCER DISEASE
4
Q
What are the two hookworm species that can cause Fe-deficiency anemia in the elderly population of developing countries?
A
ANCYLOSTOMA + NECATOR
5
Q
What is the most common cause of Fe-deficiency anemia in the elderly population of the western world?
A
COLON POLYPS/CARCINOMA
6
Q
In the EARLY Stage of Fe-Deficiency anemia, is the anemia MICROCYTIC, NORMOCYTIC, or MACROCYTIC?
A
NORMOCYTIC ANEMIA
Bone marrow makes the sacrifice in NUMBER (DECREASED NUMBER) for normal-sized RBCs
7
Q
KOILONYCHIA
A
Spoon-shaped nails
8
Q
Which anemia presents with koilychia + pica?
A
Fe-DEFICIENCY ANEMIA
9
Q
Which anemia presents with HIGH FREE ERYTHROCYYTE PROTOPORPHYRIN (FEP)?
A
Fe-DEFICIENCY ANEMIA
ANEMIA OF CHRONIC DISEASE
Both resulting in LOW Fe
10
Q
What is the most commonly associated syndrome with Fe Deficiency Anemia?
A
PLUMMER VINSON SYNDROME
11
Q
ANEMIA + ESOPHAGEAL WEBS (Resulting in dysphagia) + ATROPHIC GLOSSITIS (resulting in beefy-red tongue)
A
PLUMMER VINSON DYNROME
12
Q
What is the most common type of anemia in HOSPITALIZED pts?
A
Anemia of CHRONIC DISEASE (chronic inflammation OR cancer)
13
Q
What is the one main difference of lab values between Fe-DEFICIENCY ANEMIA and ANEMIA of CHRONIC DISEASE?
A
FE-DEFICIENCY ANEMIA: Low serum FER/High TIBC - Storage Fe will be used since there is low Fe in the blood
ANEMIA OF CHRONIC DISEASE: High serum FER/Low TIBC - Chronic disease -> Release of Hepcidin (acute phase reactant) -> Sequesters Fe in storage sites
14
Q
What is the first step of protorpophyrin synthesis? What is the required co-factor? Why is this step important kinetically?
A
SuccinylCoA -> ALA (aminolevulinic acid)
Enz: ALA Synthase
Co-factor: VitB6
Rate-limiting step
15
Q
Where does the last step of protoporphyrin (PP) synthesis occur? Which enzyme combines PP with Fe to form heme?
A
Mitochondria
FERROCHELATASE
16
Q
In SIDEROBLASTIC ANEMIA, where does the Fe accumulate? What histological cell in the bone marrow confirms this finding of sideroblastic anemia?
A
MITOCHONDRIA
Ringed sideroblasts - Fe accumulation in mitochondria** surrounding nucleus of erythroblasts in a ring pattern
17
Q
SIDEROBLASTIC ANEMIA can be a side effect of taking which drug?
A
ISONIAZID Treatment for TB - Pts taking INH can become VitB6 deficient -> Important co-factor for the ALAS -> Protoporphyrin deficient -> SIDEROBLASTIC ANEMIA
18
Q
Which disease has the same laboratory findings as sideroblastic anemia? How would you characterize the state for both of these conditions?
A
HEMACHROMATOSIS
Both FE-OVERLOADED STATE: High FER/Low TIBC + High serum Fe/High % saturation
19
Q
What is the most common CONGENITAL cause of SIDEROBLASTIC ANEMIA?
A
ALAS Deficiency - Rate limiting step enzyme
20
Q
Which 3 poisonings can result in ACQUIRED SIDEROBLASTIC ANEMIA?
A
ALCOHOL - Mitochondrial damage
LEAD - Denatures ALAD, FERROCHELATASE
ISONIAZID (INH) - Reduces VitB6 (co-factor of ALAS)
21
Q
What explains the high genetic frequency and thus prevalence of THALASSEMIA?
A
Inherited mutation offers protection against PLASMODIUM FALCIPARUM MALARIA
22
Q
What is the most common inherited mutation of ALPHA THALASSEMIA? What is the most common inherited mutation of BETA THALASSEMIA? What chromosomes do each of these alleles lie?
A
ALPHA - GENE DELETION CHROM 16
BETA - GENE MUTATION CHROM 11
23
Q
What are the two types of 2 gene deletions of ALPHA THALASSEMIA? Which has a worse clinical picture?
A
- CIS-DELETION - Both alleles on 1 copy of Chrom 16 are lost
- TRANS-DELETION - One allele from each copy of Chrom 16 is lost
CIS-DELETION = Worse clinical picture
24
Q
Which population is cis-deletion ALPHA THALASSEMIA more prevalent in? Which population is trans-deletion ALPHA THALASSEMIA more prevalent in?
A
CIS-DELETION: Asia - Believed to explain the higher rate of spontaneous abortions in Asia
TRANS-DELETION: Africa
25
How does one confirm a 3-gene deletion ALPHA THALASSEMIA?
HbH (beta4 tetramer) can be detected via ELECTROPHORESIS
IN UTERO: 3-gene alpha chain deletion is SUFFICIENT
POST-BIRTH: HbH: beta dimer (beta2) can't bind to alpha dimer (alpha2) -> beta2 binds to another beta2 -> beta4
26
How does one confirm 4-gene deletion ALPHA THALASSEMIA?
Hb Barts (gamma4) can be seen on electrophoresis
IN UTERO: Lethal (Hydrops fetalis) - Formation of GAMMA4 (Hb Barts) - Gamma dimer (Gamma2) does not have alpha2 dimer to bind with -> Binds with another gamma2 -> Gamma tetramer
27
What is the key finding on electrophoresis of BETA THALASSEMIA MINOR (b/b+)?
ISOLATED INCREASE in HbA2 (alpha2delta2)
28
What is the most mild form of beta thalassemia? What is the most severe form of beta thalassemia?
BETA THALASSEMIA MINOR (b/b+) - most mild
| BETA THALASSEMIA MAJOR (bo/bo) - most severe
29
In managing BETA THALASSEMIA MAJOR, chronic transfusions are often given. What is a complication that the pt is at risk for in receiving this treatment?
SECONDARY HEMOCHROMATOSIS - Every time pt is getting transfusion, he/she receives bag of Fe as well as RBC -> Excess Fe builds up in tissue as body has no physiological means of eliminating Fe
30
Crewcut appearance on X-ray + Chipmunk-face are indicative of __?
BETA THALASSEMIA MAJOR or SICKLE CELL ANEMIA - Due to expansion of hematopoiesis in skull (crewcut) + facial bones by massive erythroid hyperplasia due to severe anemia
31
BETA THALASSEMIA MAJOR, HEREDITARY SPHEROCYTOSIS, and SICKLE CELL ANEMIA pts are at risk of APLASTIC CRISIS with which type of infection?
PARVOVIRUS B19 infection inhibits erythroid precursors from producing mature RBC for 1-2wks
32
What are the three complications of BETA THALASSEMIA MAJOR and SICKLE CELL ANEMIA
1. Hematopoiesis in skull + facial bones
2. Extramedullary hematopoiesis in spleen -> HEPATOSPLENOMEGALY (beta thalassemia), HEPATOMEGALY (sickle cell, since sickle cell pts generally don't have a spleen)
3. Risk of APLASTIC CRISIS with Parvovirus B19 infection
33
Blood Smear: MICROCYTIC, HYPOCHROMIC RBC + TARGET CELLS + NUCLEATED RBC.
Which RBC disorder am I?
BETA THALASSEMIA MAJOR (bo/bo)
Not beta thalassemia minor (b/b+) - microcytic hypochromic RBC + target cells. Anemia is not severe enough. In beta thalassemia major, anemia is SEVERE to a point that massive erythroid hyperplasia occurs -> expansion of hematopoiesis (particularly erythropoiesis) in the skull, facial bones, spleen -> some nucleated RBC escape
34
What is the isolated key finding of BETA THALASSEMIA MAJOR on electrophoresis?
```
LITTLE or NO HbA (alpha2beta2)
INCREASED HbA2 (alpha2delta2), HbF (alpha2,gamma2)
```
35
Why do RETICULOCYTES have slightly bluish cytoplasm?
Reticulocytes = BABY RBC (larger in size with bluish cytoplasm)
RESIDUAL RNA within cytoplasm
36
What lab data does one use to distinguish between normocytic anemia due to PERIPHERAL RBC DESTRUCTION (i.e. HEMOLYSIS) and normocytic anemia due to BONE MARROW UNDERPRODUCTION?
RETICULOCYTE COUNT (RC) - Normally 1-2%
*RC>3% - GOOD BONE MARROW RESPONSE (Bone marrow is able to respond by increasing RC to try to make up for the loss of RBC) + PERIPHERAL RBC PRODUCTION (Intravascular OR extravascular)
RC
37
Where do you see bone marrow hyperplasia with RETICULOCYTE COUNT (adjusted) >3%? Normocytic anemia due to EXTRAVASCULAR HEMOLYSIS or INTRAVASCULAR HEMOLYSIS?
BOTH
RETICULOCYTE COUNT (adjusted)>3% for both since RBC destruction is occurring peripheral to the bone marrow with a good bone marrow response
38
Which hemolytic normocytic anemia do you see ANEMIA with SPLENOMEGALY and JAUNDICE? Intravascular or extravascular? Explain why.
EXTRAVASCULAR
SPLENOMEGALY - Extravascular hemolysis (Splenic macrophages are consuming the RBC) -> Splenic hypertrophy = SPLENOMEGALY
JAUNDICE = Buildup of serum INDIRECT/UNCONJUGATED Bilirubin (breakdown product of protoporphyrin from HGB breakdown after splenic macrophages consume the RBC). Liver can not keep up in its conjugation rate of the indirect bilirubin bec so many RBC are being lysed
39
Which hemolytic normocytic anemia do you see ANEMIA with an INCREASED RISK of BILIRUBIN GALLSTONES? Intravascular or extravascular? Explain why.
Extravascular
Buildup of INDIRECT/UNCONJUGATED Bilirubin in the bloodstream -> Eventually gets conjugated in the liver -> Dumped into the bile in the gallbladder.
Supersaturation of BILIRUBIN in the bile = BILIRUBIN GALLSTONES
40
What is the first change in clinical lab data when assessing for normocytic anemia with INTRAVASCULAR hemolysis?
DECREASED HAPTOGLOBIN - HGB leaks out from RBC and gets immediately picked up by serum haptoglobin -> Delivered to the spleen for recycling of Fe and HGB
41
What are the significant urinalysis values in determining normocytic anemia with INTRAVASCULAR HEMOLYSIS? (Hint: 1 first, followed by another a few days later)
1. First, HEMOGLOBINURIA - HGB leaked from the RBC into the blood -> Leaks into the urine
2. Few days later, HEMOSIDERINURIA - Some of the H2O-soluble HGB is picked up by renal tubular cells -> Broken down -> Fe accumulates into HEMOSIDERIN -> Sloughed off tubular cells -> hemosiderinuria
42
Name the 3 main NORMOCYTIC ANEMIAS with PREDOMINANT EXTRAVASCULAR HEMOLYSIS.
1. HEREDITARY SPHEROCYTOSIS
2. SICKLE CELL ANEMIA - E6V: Autosomal recessive
3. HGB C - E6K (HB C HAS LYSSSSSINE): Autosomal recessive
43
What is the inherited defect in HEREDITARY SPHEROCYTOSIS?
Defect in RBC cytoskeletal-membrane tethering proteins
44
What are the most common RBC cytoskeletal-membrane tethering proteins that maintain its BICONCAVE shape? (3)
'ABS-Shape'
1. ANKYRIN
2. BAND 3.1
3. SPECTRIN
45
DDx of having INCREASED MCHC (Mean corpuscular HGB Concentration). Describe the mechanism of which MCHC is increased.
1. HEREDITARY SPHEROCYTOSIS
2. AUTOIMMUNE ANEMIA
As the cell is shrinking down, cytoplasm remains about the same. Apparent [HGB] INCREASES
46
Which 3 anemias have the complication of increased risk of APLASTIC CRISIS with PARVOVIRUS B19 Infection of erythroid precursors?
1. BETA THALASSEMIA MAJOR
2. HEREDITARY SPHEROCYTOSIS
3. SICKLE CELL DISEASE
47
What is the diagnostic test for HEREDITARY SPHEROCYTOSIS?
OSMOTIC FRAGILITY TEST on HYPOTONIC SOLN
Normal RBC (YES BICONCAVE CENTER): Fairly resistant to hypotonic solution -> Water entering the RBC -> Biconcave center has room for it to expand without bursting
SPHEROCYTE (NO BICONCAVE CENTER): Increased fragility (bursting) to hypotonic solution
48
What is the Tx for HEREDITARY SPHEROCYTOSIS?
SPLENECTOMY - Resolves anemia since splenic macrophages can no longer consume the spherocytes
49
Will the spherocytes disappear when pts with HEREDITARY SPHEROCYTOSIS receive a splenectomy?
NO
Because the inherited defect of cytoskeletal-membrane proteins still exist -> Membrane blebs will still form outside the RBC -> Other macrophages in the RES other the spleen (liver, lymph node) will consume the blebs -> Spherocytes will still form
50
What histological finding will be seen in pts with hereditary spherocytosis receive a splenectomy?
HOWELL-JOLLY BODIES on blood smear
No spleen, Can NO longer get rid of nuclear fragment that accidentally remained in the RBC
51
What lab findings will confirm HEREDITARY SPHEROCYTOSIS? (Hint: RDW and MCHC, Blood smear)
Blood Smear: Spherocytes with NO central pallor (loss of biconcave center)
INCREASED RDW - Continual membrane bleb loss, young spherocytes will have the least membrane loss = bigger, older spherocytes will have the most membrane loss = smallest
INCREASED MCHC - Cell shrinkage without any change in cytoplasm -> Increased apparent [HGB]
52
What is the inheritance pattern of sickle cell disease? What is the mutation?
AUTOSOMAL RECESSIVE
| E6V: Glu (Hydrophilic) -> Val (Hydrophobic)
53
What 3 conditions of stress increase the risk of sickling?
HYPOXIA, ACIDOSIS, DEHYDRATION
54
What is a protective factor against sickling?
HbF
55
Why does sickle cell not manifest itself until 6mo of age?
Bec HbF is the predominant HGB being produced until 6mo and will offer a protective role
56
What is the medication given to pts with Sickle cell disease? What is its mechanism?
HYDROXYUREA - Increases HbF
57
What is the most common presenting sign of sickle cell disease in infants >6mo old?
DACTYLITIS (Vaso-occlusive infarct of the bone due to irreversible sickling)
Swelling of the hands and feet
58
What is the most common cause of death in sickle cell children?
INCREASED RISK OF INFECTION by encapsulated organisms [haemophilus + strep pneumo] after autosplenectomy (vaso-occlusive crisis in spleen due to irreversible sickling)
59
What is the most common cause of death in sickle cell adults?
ACUTE CHEST SYNDROME:
Pneumonia -> Decreased SVR and pulmonary circulation vasodilation -> Increased RBC transit time under stress -> Increased sickling -> Acute chest syndrome
60
What is the most common cause of osteomyelitis? What is the most common cause of osteomyelitis in sickle cell disease pts?
S. AUREUS
| Salmonella paratyphi - sickle cell disease
61
Ddx of HOWELL-JOLLY BODIES (in context of anemias) on blood smear:
HOWELL JOLLY BODIES = SPLENIC DYSFUNCTION OR SPLENECTOMY
1. post-splenectomy pts with HEREDITARY SPHEROCYTOSIS
2. AUTOSPLENECTOMY vaso-occlusive crisis of the spleen due to irreversible sickling in SICKLE CELL DISEASE
62
How does sickle cell vaso-occlusive crises from irreversible sickling impact the kidney?
Vaso-occlusive crisis of the kidney -> RENAL PAPILLARY NECROSIS - Gross hematuria + proteinuria
63
Will there be any change in serum HAPTOGLOBIN with sickle cell disease?
YES, DECREASED SERUM HAPTOGLOBIN
Sickle cell disease is predominantly EXTRAVASCULAR HEMOLYSIS (continuous sickling and de-sickling as it continues through micro-circulation) BUT surviving RBC can also lyse within BV (INTRAVASCULAR HEMOLYSIS)
64
What two types of cells will be seen in the blood smear of SICKLE CELL DISEASE?
1. TARGET CELLS - As RBC begins to dehydrate, cytoplasm decreases -> Membranes outfold -> Bleb full of HGB form in the biconcave center
2. SICKLE CELLS - Polymerization of HbS
65
Will SICKLE CELL DISEASE or SICKLE CELL TRAIT or both have a POSITIVE METABISULFATE screen?
METABISULFATE - Detects the presence of ANY amt of HbS by inducing cells to sickle
BOTH will have a positive metabisulfate screen
66
What are the findings of HGB electrophoresis for sickle cell disease?
92% HbS (>90%HbS with 2 abnormal beta genes)
8% HbF, 2% HbA2
ZERO HbA
67
What are the findings of HGB electrophoresis for sickle cell trait?
55% HbA (normal) NO sickle cell since that's only seen with >50%HbS
43% HbS, 2% HbA2
68
Pts with the sickle cell trait will generally be ASYMPTOMATIC except for which area of the body? What is their first presenting Sx and the presenting Sx thereafter?
RENAL MEDULLA: Hypertonicity + extreme hypoxia cause sickling -> Micro-infarctions ->
FIRST: Microscopic hematuria
EVENTUALLY: Decreased ability to concentrate the urine
69
What is HEMOGLOBIN C DISORDER?
Autosomal recessive mutation (E6K) that results in mild anemia due to extravascular hemolysis
70
What histological feature is seen on the blood smear for pts with HGB C DISORDER?
HGB C crystals
| Rectangular crystal
71
Is PAROXYSMAL NOCTURNAL HEMOGLOBINURIA inherited or acquired?
ACQUIRED mutation in MYELOID STEM CELL
72
What do pts with PNH lack on the surface of RBC, WBC, and platelets? What is its normal mechanism of action?
GPI - Anchors DAF (CD55, which accelerates decay of C3 convertase complement) + MIRL (CD59, Membrane inhibitor of reactive lysis)
73
What is the main stimulus for HEMOGLOBINURIA in PNH?
During sleep, everyone's breathing becomes slightly shallow -> Respiratory acidosis -> Activates complement cascade
*Sucrose can also activate complement cascade (used as diagnostic test)*
PNH: NO GPI -> No anchoring of DAF and MIRL on RBC -> INTRAVASCULAR HEMOLYSIS -> HGB leaks into urine -> dark urine in the morning (HEMOGLOBINURIA)
74
What is the main cause of death in pts with PNH?
THROMBOSIS in hepatic/portal/cerebral veins
Due to complement-mediated damage of platelets (NO GPI in MYELOID STEM CELL= NO DAF = No inactivation of complement) -> Fragments of destroyed platelets -> Activate coag cascading
75
What are the two possible complications of PNH?
1. FE-DEFICIENCY ANEMIA: Constant intravascular hemolysis -> Loss of HGB containing Fe into the urine
2. ACUTE MYELOGENOUS LEUKEMIA (AML): Very easy to acquire another mutation in the myeloid stem cell
76
Is G6PD Deficiency inherited or acquired?
INHERITED X-linked recessive
77
What are the two variants of G6PD DEFICIENCY?
1. AFRICAN VARIANT - Mildly reduced half-life of G6PD -> Mild Intravascular hemolysis with oxidative stress
2. MEDITERRANEAN VARIANT - Markedly reduced half-life of G6PD -> Severe intravascular hemolysis with oxidative stres
78
Hemoglobinuria + Bite cells + Heinz bodies + Back pain
| What am I?
HEMOGLOBINURIA - Automatically think intravascular hemolysis
G6PD DEFICIENCY ANEMIA with predominant intravascular hemolysis
79
What is the confirmatory study for G6PD Deficiency Anemia? Is it time-sensitive?
ENZYME STUDY
Yes, it is time sensitive - Have to do the study AFTER the acute intravascular hemolytic episode resolves bec. if it were conducted during the episode, dead RBC most likely have the deficiency of G6PD whereas the live RBC survived due to a reduced half-life of G6PD sufficient enough to survive the oxidative stress-mediated intravascular hemolysis
80
What is the most common cause of IMMUNE HEMOLYTIC ANEMIA (specifically IgG-mediated)?
SLE - Production of Abs against RBC, platelets, WBC
81
What leukemia and drugs is Ig-G mediated IMMUNE HEMOLYTIC ANEMIA associated with?
1. CLL
| 2. Drugs - e.g. penicillin, L-methyldopa
82
Which Ab in IMMUNE HEMOLYTIC ANEMIA mediates EXTRAVASCULAR HEMOLYSIS? Which Ab in IMMUNE HEMOLYTIC ANEMIA mediates INTRAVASCULAR HEMOLYSIS?
IgG = EXTRAVASCULAR (WARM Agglutinin - binds RBC in Warmer temperatures)
IgM = INTRAVASCULAR (COLD Agglutinin - binds RBC in colder temperatures [e.g. fingers/toes])
83
What two disease states is strongly associated with IgM-mediated IMMUNE HEMOLYTIC ANEMIA?
1. MYCOPLASMA PNEUMONIAE INFECTION
| 2. INFECTIOUS MONONUCLEOSIS
84
DDx of SPHEROCYTES on blood smear
1. HEREDITARY SPHEROCYTOSIS
| 2. Ig-G MEDIATED IMMUNE HEMOLYTIC ANEMIA
85
What are the 5 NORMOCYTIC ANEMIAS WITH PREDOMINANT INTRAVASCULAR HEMOLYSIS?
1. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
2. GLUCOSE 6 PHOSPHATE DEHYDROGENASE DEFICIENCY
3. IMMUNE HEMOLYTIC ANEMIA
4. MICROANGIOPATHIC HEMOLYTIC ANEMIA
5. MALARIA
86
What is malaria? How is it transmitted?
RBC and liver infection by PLASMODIUM species.
Transmitted by ANOPHELES female mosquito
87
What is the predominant defining feature of malaria depending on the plasmodium species?
CYCLICAL FEVER - Each time the RBC rupture, correlated with Plasmodium life cycle -> Intravascular hemolysis
88
How frequent is the fever in P. falciparum-infected malaria
DAILY
89
How frequent are the fevers in P. ovale and P. vivax-infected malaria?
EVERY OTHER DAY
90
Name the 3 classes of etiologies for NORMOCYTIC ANEMIA due to UNDERPRODUCTION?
1. Any MICROCYTIC or MACROCYTIC anemia
2. RENAL FAILURE - Loss of EPO production
3. Damage to bone marrow precursor cells
91
What is the pathologic process that displaces bone marrow hematopoiesis and result in PANCYTOPENIA?
MYELOPHTHISIC PROCESS
92
What does APLASTIC ANEMIA look like on biopsy?
EMPTY MARROW with FAT ADIPOCYTES and no hematopoietic elements
93
When there is anemia of chronic disease (e.g. autoimmune disease, cancer, endocarditis), which acute phase reactant is released from the liver? What are its 2 effects?
HEPCIDIN
1. Sequesters away Fe in storage sites (macrophages and liver)
2. Suppresses EPO production to prevent further RBC production
94
What treatment may work for cancer pts who have microcytic anemia?
EXOGENOUS EPO
Since the production of EPO was suppressed by HEPCIDIN
95
In SIDEROBLASTIC ANEMIA, how does lead poisoning cause it?
Lead can denature ALAD and FERROCHETALASE - two enzymes required in the pathway of protoporphyrin production
96
Name the two MEGALOBLASTIC MACROCYTIC ANEMIAS
FOLATE DEFICIENCY
| VitB12 DEFICIENCY
97
Where is folate obtained from and where is it absorbed?
DIET (green vegetables/fruits)
| Absorbed in the JEJUNUM
98
Which drug can result in FOLATE DEFICIENCY MACROCYTIC MEGALOBLASTIC ANEMIA?
METHOTREXATE - INHIBITS DHF REDUCTASE and thus inhibits THF (folate) production required for THYMIDYLATE SYNTHASE's conversion of dUMP to dTMP -> Cell can no longer divide -> 1 less division = MACROCYTIC ANEMIA
99
How does one differentiate in lab findings between FOLATE DEFICIENCY and VITB12 DEFICIENY?
FOLATE DEFICIENCY = Normal methylmalonic acid = Byproduct of FATTY ACID OXIDAITON
VITB12 DEFICIENCY = ELEVATED methylmalonic acid since VitB12 is required for the conversion of MeMalonic acid -> SuccinylCoA
100
Will hypersegmented neutrophils and megaloblastic changes in other rapidly dividing cells be presented in MACROCYTIC anemia due to alcoholism, liver disease, and drugs (5-FU)?
NO - Because these macrocytic anemias are NOT megaloblastic like Folate/VitB12 deficiencies.
101
Which MACROCYTIC anemia develops first with regards to time scale and thus more common? FOLATE or VITB12 Deficiency anemia?
FOLATE DEFICIENCY occurs within first within MONTHS bec body stores are MINIMAL
VitB12 DEFICIENCY occurs within YEARS bec of LARGE HEPATIC VitB12 STORES
102
Where is VitB12 absorbed?
TERMINAL ILEUM
103
What is the most common cause of VitB12 Deficiency?
PERNICIOUS ANEMIA - Autoimmune destruction of stomach parietal cells -> Decreased IF production -> Decreased absorption of VitB12 in the ILEUM
104
PANCREATIC INSUFFICIENCY is a cause of which type of anemia? How?
VITB12 DEFICIENCY MACROCYTIC MEGALOBLASTIC ANEMIA
DECREASED PANCREATIC PROTEASES -> Decreased cleavage of VitB12 from R binder protein in the SMALL INTESTINE or VitB12 to bind to Intrinsic factor for absorption
105
What diseases can cause damage to the terminal ileum and thus cause VITB12 DEFICIENCY MACROCYTIC MEGALOBLASTIC ANEMIA?
```
CROHN'S DISEASE
DIPHYLLOBOTHRIUM LATUM (Fish tapeworm infection)
```
106
How common is dietary VitB12 Deficiency? In which population will its prevalence be higher?
VERY RARE bec of the LARGE HEPATIC VITB12 STORES
Mostly prevalent in vegans - no animal proteins are consumed
107
What are two clinical presentation sx of VitB12 Deficiency MEGALOBLASTIC MACROCYTIC ANEMIA?
1. Glossitis - Same as FOLATE DEFICIENCY
2. Subacute combined degeneration of spinal cord - Due to elevated METHYLMALONIC ACID in myelin of
Dorsal columns: POOR PROPRIOCEPTION + VIBRATION
LCST: SPASTIC PARESIS
108
What are the CONGENITAL causes of APLASTIC ANEMIA associated + PANCYTOPENIA (Bone marrow failure)?
1. FANCONI ANEMIA
| 2. DYSKERATOSIS CONGENITA
109
LAB DATA: THROMBOCYTOPENIA, ANEMIA (i.e. PANCYTOPENIA due to bone marrow failure)
Clinical Triad: Nail dystrophy + Leukoplakia + Skin hyper-pigmentation
("reticular/mottled rash")
What congenital cause of aplastic anemia am I?
DYSKERATOSIS CONGENITA
110
What is the key feature with regards to biomolecular mechanism of DYSKERATOSIS CONGENITA? Do I have an INCREASED/DECREASED/NEUTRAL risk of cancer with this congenital cause of aplastic anemia?
DISRUPTION of TELOMERE MAINTENANCE
INCREASED risk of cancer
111
What is the congenital cause of APLASTIC ANEMIA associated with PANCYTOPENIA (bone marrow failure) due to a DNA REPAIR DEFECT?
FANCONI ANEMIA
112
APLASTIC ANEMIA + HIGH INCIDENCE of progression to AML + SHORT STATURE + PANCYTOPENIA
What congenital syndrome associated with bone marrow failure am I?
FANCONI ANEMIA
113
Which drugs may be the cause of ACQUIRED APLASTIC ANEMIA?
1. CHLORAMPHENICOL - Previously used as a Tx for neisseria meningitidis
2. BENZENE
114
What viruses may cause APLASTIC ANEMIA?
PARVOVIRUS B19 infection of erythroid precursors
| DNA viruses - CMV, EBV, Hep B/C/D, HIV
115
Which anemia may be an acquired cause an APLASTIC CRISIS?
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA - acquired mutation in myeloid stem cell
116
Which drug can cause MACROCYTIC, but NOT megaloblastic anemia?
5-FU
Will show MCV >100, but no hypersegmented neutrophils or megaloblastic change in rapidly dividing intestinal epithelial cells
117
Which drug can cause MACROCYTIC MEGALOBLASTIC ANEMIA?
METHOTREXATE
Inhibits DHF Reductase - Reduces FOLATE levels (THF) -> FOLATE DEFICIENCY
MACROOVALOCYTE, HYPERSEGMENTED NEUTROPHIL, INTESTINAL EPITHELIAL HYPERPLASIA (megaloblastic change)
118
What is the theoretical definition of ANEMIA? What are used as surrogate markers? Why are they called "Surrogate"
ANEMIA = Decrease in RBC mass
| Surrogate markers = HGB, HCT, RBC Ct = Surrogate bec they're concentration dependent
119
There are two major instances when HGB, HCT become POOR surrogates of RBC mass (hypoxia). Name them and how the values change. [HINT: Think 1 female repro, 1 emergency]
PREGNANCY: Normal RBC mass, but overall volume increases
Decreased HGB, HCT as overall volume dilutes it
Can see MACROCYTIC ANEMIA (MCV>100) due to folate deficiency - increased demand by baby
CARDIOGENIC SHOCK (GUN SHOT WOUND):
At first, BOTH RBC and fluid are being lost - Will present as NORMAL HGB, HCT
After hydration, Dilution of remaining RBC - Will present as Decreased HGB, HCT
120
What is the Tx of FE-DEFICIENCY ANEMIA? What is the Tx of ANEMIA OF CHRONIC DISEASE?
FE-DEFICIENCY ANEMIA: Exogenous Ferrous sulfate (Fe2+) and the underlying cause (e.g. colonic polyps/colonic carcinoma/peptic ulcer disease)
ANEMIA OF CHRONIC DISEASE: Exogenous EPO (especially cancer pts will have suppressed EPO by HEPCIDIN)
121
What is the difference between THALASSEMIA and SICKLE CELL ANEMIA?
THALASSEMIA = Decreased globin SYNTHESIS -> Resulting in Low HGB = Anemia
SICKLE CELL ANEMIA = Mutational abnormality in globin chain POST-synthesis = Anemia
122
What is the difference between MEGALOBLASTIC MACROCYTIC ANEMIA and MACROOVALOCYTIC ANEMIA? Name the main etiologies for each.
MEGALOBLASTIC ANEMIA: MACRO-OVALOCYTE (MCV>100) + Megaloblastic change to rapidly dividing cells (e.g. intestinal epithelial cells) + Hypersegmented neutrophils (>5 lobes)
Causes: VITB12/FOLATE deficiency -> Decreased THF required for DNA precursor synthesis necessary for a RBC division -> 1 less division = Macrocytic anemia
MACRO-OVALOCYTIC ANEMIA: MACRO-OVALOCYTE (MCV>100) only
Causes: ALCOHOLISM, LIVER FAILURE, DRUGS (5-FU)
123
* *UW:
1. ANEMIA due to defective mRNA Tx, processing, and translation = ?
2. ANEMIA due to reduction of membrane cytoskeleton and stability = ?
3. ANEMIA due to DNA synthesis defects = ?
4. ANEMIA due to impaired intracellular oxidant detox = ?
1. BETA THALASSEMIA MINOR: Pre-full synthesis of beta-globin in mRNA processing
2. BETA THALASSEMIA MAJOR: Pre-full synthesis of beta-globin -> alpha4 tetramers -> Precipitate within RBC and affect membrane stability
3. MEGALOBLASTIC ANEMIA (VitB12, folate deficiency)
4. G6PD deficiency normocytic anemia with predominant intravascular hemolysis
