Anemia Flashcards
(168 cards)
1
Q
MCV in microcytic anemia
A
Less than 80 μm3
2
Q
MCV in macrocytic anemia
A
Greater than 100 μm3
3
Q
Underlying etiology of microcytic anemia
A
underproduction of Hb causes “extra divisions” in precursors to maintain RBC Hb concentration
4
Q
Underlying etiology of macrocytic anemia
A
Error in DNA synthesis causes “too few divisions” in precursors, which get stuck in G2
5
Q
Underlying etiology of normocytic anemia
A
Destruction (peripheral and/or intravascular), or underproduction
6
Q
Reticulocyte count in normocytic anemias
A
corrected retic >3%: destruction with normal marrow response
corrected retic
7
Q
Cause of iron deficiency anemia in infants
A
Breast feeding
8
Q
Cause of iron deficiency anemia in children
A
poor diet
9
Q
Cause of iron deficiency anemia in adults
A
PUD in males
menorrhagia or pregnancy in females
Malabsorption (e.g. celiac’s)
Gastrectomy
10
Q
Cause of iron deficiency anemia in elderly
A
Colon polyps/carcinoma, hookworm
11
Q
Trace the path of iron from intake to storage (5 steps)
A
1) Intake via heme and non-heme forms
2) Duodenal enterocytes uptake via DMT1
3) Passed through enterocyte cytosol via ferroportin
4) Enters bloodstream attached to transferrin
5) Stored in hepatic and marrow macrophages via ferritin
12
Q
Normal Hb in males
A
13.5 - 17.5
13
Q
Normal Hb in females
A
12.5 - 16.0
14
Q
Stages of iron deficiency, with [Ferritin, TIBC, Serum Fe, %saturation, RBC, and MCV] findings
A
1) Storage is depleted (↓Ferritin, ↑TIBC)
2) Serum is depleted (↓Serum Fe, ↓%saturation)
3) Normocytic anemia (↓RBC, MCV is NL)
4) Microcytic, hypochromic anemia (↓RBC, MCV)
15
Q
Labs in IDA (RBC and serum)
A
1) Microcytic, hypochromic RBCs w/↑RDW
2) ↓Ferritin, ↑TIBC, ↓Serum Fe, ↓%sat, ↑FEP
16
Q
Iron deficiency anemia with esophageal web and atrophic glossitis
A
Plummer-Vinson syndrome
17
Q
MCV in normocytic anemia
A
80 - 100 μm3
18
Q
Lab findings in anemia of chronic disease
A
↑Ferritin, ↓TIBC, ↓Serum Fe, ↓%saturation, ↑FEP
19
Q
Tx of anemia in chronic kidney disease
A
EPO
20
Q
Trace the path of iron from intake to storage (5 steps)
A
1) Intake via heme and non-heme forms
2) Duodenal enterocytes uptake via DMT1
3) Passed through enterocyte cytosol via ferroportin
4) Enters bloodstream attached to transferrin
5) Stored in hepatic and marrow macrophages via ferritin
21
Q
Normal Hb types
A
HbA (α2 β2)
HbA2 (α2 δ2)
HbF (α2 γ2)
22
Q
Why does gastrectomy cause IDA?
A
Higher pH results in higher proportion of Fe+3, which is less readily absorbed
23
Q
Labs in IDA (RBC and serum)
A
1) Microcytic, hypochromic RBCs w/↑RDW
2) ↓Ferritin, ↑TIBC, ↓Serum Fe, ↓%sat, ↑FEP
24
Q
Iron deficiency anemia Tx
A
Ferrous sulfate
25
Iron deficiency anemia Sxs (4)
Fatigue
Conjunctival pallor
Pica
Koilonychia
26
Heme synthesis pathway
```
Succinyl CoA -[ALAS, B6]→
ALA -[ALAD]→
porphobilinogen -[in mitochondrion]→
protoporphyrin + Fe -[ferrocheletase]→
Heme
```
27
General etiology of sideroblastic anemias
Decreased protoporphyrin synthesis → decreased heme synthesis
28
General etiology of iron deficiency anemia
decreased iron intake → decreased heme synthesis
29
Why does sideroblastic anemia present with ringed sideroblasts in marrow?
iron collects in mitochondria, which circle erythroblast nuceus
30
What are the causes of sideroblastic anemia?
```
Congenital ALAS deficiency
Alcoholism (mitochondrial poison)
Lead poisoning (inhibits ALAD and ferrochelatase)
Vitamin B6 deficiency (ALAS cofactor)
```
31
What anti-microbial can cause sideroblastic anemia?
Isoniazid
32
Lab findings in sideroblastic anemia
↑Ferritin, ↓TIBC, ↑Serum Fe, ↑%saturation (iron overload)
33
What is the mechanism by which chronic inflammation causes anemia?
Liver produces hepcidin, which inhibits:
1) Fe inhibits ferroportin @ macrophages and enterocytes
2) EPO production by kidney
34
Viral pathogen associated with severe Sxs in β-thalassemia major
Parvovirus B19 (aplastic crisis)
35
Tx of anemia in chronic kidney disease
EPO
36
General etiology of anemia in thalassemia?
Decreased globin production, due to congenital defects in genes encoding globin subunits
37
Thalassemia carriers are resistant to what infection?
Plasmodium falciparum
38
Thalassemia: Sxs associated with single α deletion
Asymptomatic
39
Thalassemia: Sxs associated with two α deletions
Mild anemia, ↑RBC
40
Agents used to treat lead poisoning
Dimercaprol and EDTA; succimer in kids
41
Hb type seen in α-thalassemia with three deletions
HbH (β4); damages RBC membranes
42
Thalassemia: Sxs associated with four α deletions
Hydrops fetalis, Hb Barts on electrophoresis
43
Hb type seen in α-thalassemia with four deletions
Hb Barts (γ4); damages RBC membranes
44
α deletion most prevalent in Asian populations
Cis deletion
45
General findings in megaloblastic anemia
macrocytic RBCs, hypersegmented PMNs, glossitis
46
Mutations causing β-thalassemia
Point mutations in splicing or promoter sites
47
β alleles
β0 - no production
β+ - reduced production
β - wild type
48
Sxs in β-thalassemia minor
Usually asymptomatic
49
Lab findings in β-thalassemia minor
Microcytic hypochromic anemia with target cells
| Increased HbA2 and HbF
50
Sxs in β-thalassemia major
Severe anemia months after birth
Marrow expansion: "crew cut" skull x-ray, "chipmunk" facies
Extramedullary hematopoiesis: HSM
Chronic transfusions → 2ndary hemochromatosis
51
Lab findings in β-thalassemia major
Microcytic, hypochromic RBCs w/target cells and nucleated RBCs on smear
HbA2 and HbF, little to no HbA
52
Viral pathogen associated with severe Sxs in β-thalassemia major
Parvovirus B19 (aplastic crisis)
53
Mechanism of anemia in β-thalassemia major
Precipitation of unpaired α chains damages membranes, causing ineffective erythropoiesis and extravascular hemolysis
54
Phenotype for HbS/β-thalassemia heterozygote
mild to moderate sickle cell disease
55
"Burton lines"
Lead lines on gingiva
56
Demyelinating damage in B12 deficiency occurs at:
1) Spinocerebellar tract
2) Lateral corticospinal tract
3) Dorsal column
57
Type of anemia seen in lead poisoning
Microcytic sideroblastic anemia
58
Mechanism causing anemia in lead poisoning
Inhibition of ferrochelatase and ALAD causing decreased heme synthesis
59
Agents used to treat lead poisoning
Dimercaprol and EDTA; succimer in kids
60
Treatment for sideroblastic anemia
pyridoxine (B6)
61
Mechanism by which folate and B12 deficiency cause anemia
Folate is demethylated by B12, allowing it to participate in the production of DNA precursors. Deficiency in either inhibits DNA synthesis, which inhibits erythropoiesis
62
PMN findings and their cause in Megaloblastic anemia
Impaired maturation of granulocyte precursors due to deficient DNA synthesis causes hypersegmentation of PMN nuclei.
63
Findings in Diamond-Blackfan anemia
1) ↓Hb, ↑%HbF
2) Short stature
3) Craniofacial abnormalities
4) Triphalangeal thumbs
64
General findings in megaloblastic anemia
macrocytic RBCs, hypersegmented PMNs, glossitis
65
Folate intake and absorption
green vegetables and some fruits; absorbed in jejunum
66
Causes of folate deficiency (4)
Malnutrition (esp. alcoholism)
Malabsorption
Increased requirement (pregnancy, cancer, hemolytic anemia)
Drugs (esp. folate metabolism antagonists, phenytoin)
67
Clinical and lab findings in folate deficiency megaloblastic anemia (4)
1) macrocytic RBCs and hypersegmented PMNs
2) Glossitis
3) ↓ serum folate
4) ↑ homocysteine
68
Findings that differentiate folate deficiency from B12 deficiency
No neuro sxs, normal methylmalonic acid
69
B12 intake and absorption pathway
1) intake via animal proteins
2) Salivary enzymes liberate B12
3) Salivary R-binder binds B12
4) Pancreatic proteases in duodenum liberate B12
5) Intrinsic factor (made by gastric parietal cells) binds B12 in the small bowel
6) IF-B12 complex absorbed in the ileum
70
Cause of pernicious anemia
Anti-gastric parietal cell Abs cause IF deficiency, leading to B12 deficiency
71
Causes of B12 deficiency (5)
1) Pernicious anemia
2) Poor intake (veganism, alcoholism)
3) Malabsorption in terminal ileum
4) Diphyllobothrium latum
5) Gastrectomy
72
Clinical and lab findings in B12 deficiency
1) Macrocytic RBCs and hypersegmented PMNs
2) Glossitis
3) ↓Serum B12
4) ↑ homocysteine
5) ↑methylmalonic acid
6) Subacute degeneration of spinal cord→poor proprioception, poor vibration sensation, spastic paresis
73
Cause of spinal degeneration in B12 deficiency
↑ Methylmalonic acid impairs myelinization
74
Cause of ↑ risk of thrombosis in B12 and B9 deficiency
↑ homocysteine causes IV damage
75
Demyelinating damage in B12 deficiency occurs at:
1) Spinocerebellar tract
2) Lateral corticospinal tract
3) Dorsal column
76
Megaloblastic anemia with orotic acid in urine
Orotic aciduria
77
Tx in hereditary spherocytosis?
Splenectomy
78
Orotic aciduria presentation
Presents in childhood as:
1) Failure to thrive
2) Developmental delay
3) Megaloblastic anemia refractory to B12/B9 supplementation
79
Lab finding differentiating between orotic aciduria and ornithine transcarbamylase deficiency
No hyperammonemia in orotic aciduria
80
Tx in orotic aciduria
UMP
81
Rapid onset of anemia in 1st year of life due to intrinsic defect in erythroid progenitor cells
Diamond-Blackfan anemia
82
Findings in Diamond-Blackfan anemia
1) ↓Hb, ↑%HbF
2) Short stature
3) Craniofacial abnormalities
4) Triphalangeal thumbs
83
Anemia and RBC macrocytosis without hypersegmented PMNs implies
No impairment of DNA synthesis
84
Causes of nonmegaloblastic anemia
Liver disease, alcoholism, 5-FU
85
Appearance of reticulocytes
large RBC with bluish tinge
86
Reticulocyte count in normal marrow response to stress
>3% (corrected)
87
Site of RBC destruction in extravascular hemolysis
Reticuloendothelial macrophages in spleen, liver and lymph nodes
88
Products of RBC destruction by macrophages
1) Globin → amino acids
2) Heme → Fe and protoporphyrin
3) Protoporphyrin → unconjugated bilirubin
89
Excretion of unconjugated bilirubin is accomplished by:
1) Binding to serum albumin and delivery to liver
2) Conjugation to glucaronic acid to make water soluble conjugated bilirubin
3) Excretion of conjugated bilirubin into bile
90
Clinical and lab findings in extravascular hemolysis (4)
1) Anemia w/spherocytes
2) ↑LDH
3) ↑ indirect bili → jaundice and bilirubin gallstones
4) Splenomegaly
91
Clinical and lab findings in intravascular hemolysis (4)
1) Anemia w/schistocytes
2) ↑LDH
3) ↑ serum Hb, ↓ haptoglobin
4) Urine findings: hemoglobinuria, hemosiderinuria, urobilinogen in urine
92
Phenotype in HbC/HbS heterozygotes
Milder sickle cell disease than HbS homozygotes
93
Clinical and lab findings in hereditary spherocytosis (5)
1) Splenomegaly
2) Jaundice, ↑ indirect bili, and bilirubin gallstones
3) ↑LDH
4) Spherocytes, ↑MCHC
5) (+) osmotic fragility test
94
Mechanism by which spherocytes are formed in hereditary spherocytosis
Defective cytoskeleton anchoring proteins → blebbing → loss of membrane
95
Increase risk associated with pathogen in hereditary spherocytosis?
Aplastic crisis w/Parvovirus B19
96
Tx in hereditary spherocytosis?
Splenectomy
97
Presentation of PNH (3)
1) Hemoglobinuria in the morning (mild respiratory acidosis during sleep activates complement)
2) Pancytopenia
3) Venous thrombosis (esp. hepatic, portal, cerebral veins)
98
Labs in PNH (6)
1) Hemoglobinemia
2) Hemoglobinuria
3) Hemosiderinuria (days later)
4) (+) sucrose test and (+) acidified serum test
5) (-) CD55 (DAF) on flow cytometry
6) Coombs (-)
99
Sickle cell trait confers protection against
Plasmodium falciparum
100
Cause of sickling?
Hypoxemia, dehydration or acidemia cause polymerization of HbS
101
Sites of hemolysis in sickle cell anemia, and associated findings?
Extravascular: continuous sickling/unsickling damages RBC membranes, prompting removal at spleen
Associated findings: ↑ unconjugated bili → jaundice, gall stones
Intravascular: RBCs w/damaged membranes dehydrate
Associated findings: target cells, ↓haptoglobin
102
What causes anemia in G6PD deficiency? (4)
Oxidative stress, e.g.
1) Sulfa drugs + dapsone
2) Antimalarials
3) infx
4) fava beans
103
Signs of compensatory hyperhematopoiesis in sickle cell anemia
1) Chipmunk facies
2) "crew cut" skull x-ray
3) hepatomegaly
104
Vaso-occlusive complications in sickle cell anemia (5)
1) Dactylitis (common presenting sign in infants)
2) Acute chest syndrome (pulmonary microocclusion)
3) Sequestration crises and Autosplenectomy w/Howell Jolly bodies → ↑infx by encapsulated organisms (esp. salmonella osteomyelitis)
4) Renal papillary necrosis w/hematuria
5) Pain crisis (e.g. priapism)
105
Signs of acute chest syndrome in sickle cell anemia
Chest pain, SOB, lung infiltrates; most common cause of death in adults w/SSD
Often precipitated by PNA
106
Increased risk associated with viral pathogen in SSD
Aplastic crisis w/Parvovirus B19
107
Diagnosis in sickle cell trait
1) Metabisulfite screen
| 2) Hb electrophoresis
108
Primary site of sx in sickle cell trait
Kidney: hypoxia and hypertonicity in medulla causes sickling → microinfarctions → microscopic hematuria
109
Site of hemolysis in warm AIHA
Splenic macrophages eat IgG coated RBC membrane
110
Clinical and lab findings in HbC disease
1) Mild anemia due to extravascular hemolysis
| 2) HbC crystals in RBCs
111
Causes of warm AIHA (4)
1) SLE
2) CLL
3) α-methyldopa (self-antigen binding IgG)
4) Penicillin, cephalosporins (drug-membrane complex binding IgG)
112
Complications of PNH (3)
1) Hepatic, portal and cerebral venous thrombosis
2) Progression to AML
3) Iron deficiency anemia
113
Presentation of pyruvate kinase deficiency
hemolytic anemia in a newborn
114
Proportion of Hb forms in sickle cell disease and trait
Disease: HbS - 90%; HbF - 8%; HbA2 - 2%
Train: HbA - 55%; HbS - 43%; HbA2 - 2%
115
Defect in paroxysmal nocturnal hemoglobinuria
Acquired mutation in stem cell → loss of GPI anchor for DAF → disinhibition of complement mediated lysis of RBCs
116
Presentation of PNH
1) Hemoglobinuria in the morning (mild respiratory acidosis during sleep activates complement)
2) Pancytopenia
3) Venous thrombosis (esp. hepatic, portal, cerebral veins)
117
Labs in PNH
1) Hemoglobinemia
| 2)
118
Tx in PNH
eculizumab (terminal complement inhibitor)
119
Causes of cold AIHA (3)
1) CLL
2) Mycoplasma pneumoniae
3) Infectious mononucleosis
120
G6PD role in oxidative stress
1) HMP shunt: G6P → G6PD
2) This regenerates NADPH
3) NADPH regenerates GSH
4) GSH inactivates free radicals/ROS
121
What causes anemia in G6PD deficiency?
Oxidative stress, e.g.
1) Sulfa drugs + dapsone
2) Antimalarials
3) infx
4) fava beans
122
G6PD deficiency presentation
Back pain and hemoglobinuria days after oxidative stress
123
Populations with high prevalence of G6PD deficiency
1) African variant: mild reduction in G6PD half life → mild IV hemolysis
2) Mediterranean variant: marked reduction in G6PD half life → marked IV hemolysis
124
What are Heinz bodies?
Oxidative stress → sulfur crosslinking in Hb → Hb precipitation; removal in spleen → bite cells
125
When should enzyme studies by conducted in G6PD deficiency?
Weeks after the resolution of a hemolytic episode
126
Cause of hemolysis in Autoimmune Hemolytic Anemia?
IgG or IgM antibody mediated destruction
127
"Warm agglutinins"
anti-RBC IgG
128
Site of hemolysis in warm AHA
Splenic macrophages eat IgG coated RBC membrane
129
Blood smear in warm AIHA
Spherocytes
130
Causes of warm AIHA
1) SLE
2) CLL
3) α-methyldopa (self-antigen binding IgG)
4) Penicillin, cephalosporins (drug-membrane complex binding IgG)
131
Complications of PNH
1) Hepatic, portal and cerebral venous thrombosis
2) Progression to AML
3) Iron deficiency anemia
132
Etiology of acute chest syndrome in SSD following PNA?
PNA → dilation of pulmonary vessels (↑transit time) + hypoxemia → sickling
133
Tx in warm AIHA
DC causative drug, give steroids and IVIG, splenectomy if refractory
134
Defect in Fanconi anemia
DNA repair defect → marrow failure
135
Site of hemolysis in cold AIHA
Mild complement activation: RBCs inactivate complement, hemolysis @ spleen via C3b opsinization
Extreme complement activation: IV hemolysis
136
Smear in cold AIHA
spherocytes
137
Presentation in cold AIHA
Cold exposure → painful cyanotic fingers and toes
138
Causes of cold AIHA
1) CLL
2) Mycoplasma pneumoniae
3) infectious mononucleosis
139
Diagnostic testing for AIHA
Coombs testing
140
Direct Coombs
Detects Ig/C3b coated RBCs
1) Coombs reagent (anti-Ig/C3b antibodies) added to patient blood
2) Agglutination occurs if RBCs are coated with Ig/C3b
141
Indirect Coombs
Detects anti-RBC antibodies in serum
1) Coombs reagent and test RBCs added to patient serum
2) Agglutination occurs if serum contains anti-RBC antibodies
142
Microangiopathic Hemolytic Anemia pathogenesis
RBCs are mechanically damaged in the circulation
143
Causes of Microangiopathic Hemolytic Anemia (4)
1) TTP, HUS, HELLP
2) Prosthetic valves
3) Aortic stenosis
4) Malignant hypertension
144
Blood smear in Microangiopathic Hemolytic Anemia
Schistocytes
145
Complication of chronic Microangiopathic Hemolytic Anemia
Iron deficiency anemia
146
Pathogenesis of anemia in TTP
anti-ADAMTS13 antibody → ↑vWF multimers → systemic microthrombi
147
Pathogenesis of anemia in HELLP
idiopathic activation of coagulation cascade in pre-ecclampsia → system microthrombi
148
Pathogenesis of anemia in HUS
Infx mediated damage to glomerular endothelium → glomerular microthrombi
149
Infectious agents that directly rupture RBCs
Plasmodium, Babesia
150
Pathogenesis of anemia in renal failure
↓EPO
151
Pathogenesis of anemia in Parvovirus B19 infx
virus infects RBC progenitors, temporarily halting erythropoeisis
152
Tx in aplastic anemia (4)
1) DC causative agents
2) Transfusions and GM-CSF/G-CSF
3) Immunosupression (idiopathic cases may be caused by abnormal T-cell activation)
4) Bone marrow transplant (last resort)
153
Defect in Fanconi anemia
DNA repair
154
Viral agents associated with aplastic anemia (4)
1) Parvovirus B19
2) EBV
3) HIV
4) Hepatitis
155
Labs in aplastic anemia
↓reticulocytes, ↑EPO
156
Sxs in aplastic anemia (4)
1) Fatigue, malaise
2) Pallor
3) Purpura, mucosal bleeding
4) Infection
157
WBC in Cushing's sydrome/corticosteroids
1) Eosinopenia (sequestered in lymph nodes)
2) Leukopenia (apoptosis)
3) Neutrophilia (disadhesion of marginated PMNs)
158
Accumulated substrates in Pb poisoning
protoporphyrin, ALAD
159
Accumulated substrates in Acute intermittent porphyria
porphobilinogen, ALAD, coporphobilinogen (urine)
160
Accumulated substrate in porphyria cutanea tarda
Uroporphyrin
161
Sxs of acute intermittent porphyria
```
4 P's
Painful abdomen
Port-wine colored urine
Polyneuropathy
Psych disturbances
```
162
Cause of acute intermittent porphyria
Defective porphobilinogen deaminase; precipitated by
1) Cytochrome P450 inducers
2) alcohol
3) Starvation
163
Tx of acute intermittent porphyria
Glucose and heme (inhibit ALAS)
164
Defect in porphyria cutanea tarda
Uroporphyrinogen decarboxylase
165
Sx of porphyria cutanea tarda
blistering cutaneous photosensitivity
166
Mechanism of iron poisoning
Peroxidation of membrane lipids → cell death
167
Sxs of iron poisoning
Nausea, vomiting, gastric bleeding, lethargy, GI scarring and obstruction
168
Tx of iron poisoning
Dialysis and chelation therapy
1) IV deferoxamin
2) Oral deferasirox
