Disorders of Red Blood Cells Flashcards
(132 cards)
1
Q
How do you differentiate iron deficiency microcytic anemia from thalassemia microcytic anemia?
A
Look at the Rbc Distribution Width (RDW)
- Iron deficiency will have a High RDW
- Thalassemia will have a low RDW
2
Q
In the presence of an anemia what can the reticulocyte count indicate?
A
In the presence of anemia a…
High count = over production or loss of storage of RBCs
Low Count = Impaired production (bone marrow destruction)
3
Q
What are Howell Jolly bodies and what is it associated with?
A
- Nuclear remnants
- Indicative of asplenia or severe anemia
4
Q
What are targets in RBCs and what is it associated with?
A
1) Concentrations of hemoglobin
2) Assoc. with Hemoglobin C disease, Asplenia, Liver disease, Thalassemia
think: HALT said the hunter to his target
5
Q
What are Heinz bodies and what are they associated with?
A
- Large, blue intracytoplasmic inclusions attached to inner cell membrane that consists of precipitated hemoglobin
- Assoc. with G6PD, thalassemia, and Oxidant drugs (Primaquine and Dapsone)
6
Q
What enzyme is inhibited by lead poisoning?
A
Ferrochelatase, ALA dehydratase, and pyrmidine 5-nucleotidase
7
Q
When looking at a Red Cell Histogram what does a left shift indicate? Right?
A
Left = microcytic red cells Right= macrocytic red cell
8
Q
How are reticulocytes identified?
A
Polychromasia. Granular netowrk of polyribosomes/rough ER that clump and are observed with staining.
9
Q
Name the different cell types in erythropoiesis.
A
1) Proerythroblast
2) Basophilic erythroblast
3) Polychromatophilic erythroblast
4) Orthochromatophilic erythroblast
5) Reticulocyte
6) Erythrocyte
10
Q
What is the difference between an orthophilic erythroblast and a reticulocyte?
A
Reticulocyte does not have a nucleus and has polychromasia
11
Q
How long does it take for the body to respond to decreased rbcs due to anemia/blood loss?
A
7 days. It takes 5 days for maturation from stem cell to reticulocyte
12
Q
What are the effects of massive bone marrow proliferation due to untreated anemia?
A
1) Expansion of the medulla
2) Thinning of the cortical bone
3) Resporption of cancellous bone
4) Secondary Bone Formation (prominent cheekbones and skull changes)
13
Q
What is an infectious cause for pure red cell aplasia?
A
Parvovirus
14
Q
What is the cause of basophilic stippling?
A
1) Thalassemia
2) Anemia of chronic disease
3) Lead poisoning
15
Q
How can you differentiate sideroblastic anemia from other forms of microcytic hypochromic anemias?
A
Sideroblastic anemia has a high serum iron level due to the fact that this disease is caused by heme synthesis problems
16
Q
What metabolites are high in a pt. with lead poisoning?
A
1) ALA increased in urine
2) Protoporphyrin IX in blood
17
Q
Causes of macrocytosis anemia?
A
1) Rapid RBC turnover (increased reticulocytes)
2) Chronic alcoholism
3) Megaloblastic anemia
4) Orotic aciduria
18
Q
What lab value do you use to confirm B12 deficiency?
A
Serum Homocysteine or methylmalonic acid (should be elevated)
19
Q
What does hemoglobin in the urine, decreased haptoglobin, and increased bilirubin indicate?
A
Intravascular hemolysis
20
Q
What is a positive Coomb’s test indicative of?
A
Autoimmune hemolytic anemia
21
Q
How can you differentiate extravascular from intravascular hemolysis?
A
1) Intravascular will have hemoglobinemia, hemoglobinuria, and hemosiderinuria.
2) Jaundice is found in both
3) Increased erythropoietin
22
Q
Autosomal dominant disease of rbc that is due to an insufficiency of membrane skeletal proteins which results in a lack of deformability resulting in hemolysis
A
Hereditary Spherocytosis
23
Q
What proteins are affected in hereditary spherocytosis?
A
1) Spectrin
2) Ankyrin
3) Band 3
24
Q
What is the primary cause of hemolysis in hereditary spherocytosis?
A
The spleen. Cell are not able to pass through the cords of Billroth
25
What is the most likely cause of aplastic crises in a pt. with Hereditary Spherocytosis?
Parvovirus infection. This occurs because virus targets erthroprogenitor cells. Leads to decreased erythropoeisis which is constantly required for HS
26
What reaction is glucose 6 phosphate dehydrogenase involved with?
Reaction: Glucose 6 phosphate --> 6-phosphogluconate
Reduces NADP --> NADPH
27
What X linked disease results in episodic hemolysis due to a misfolding of an important protein involved with glutathione pathway which releives oxidative stress?
Glucose 6 phosphate dehydrogenase deficiency
28
What is the cause of episodic hemolysis in G6PD deficiency? What initiates this?
Oxidative stress
1) Infections
2) Typhoid fever
3) Oxidant drugs (sulfonamides, anti-malarials)
4) Fava beans
29
How do Heinz bodies form in G6PD deficiency?
The increased in oxidative stress results in the crosslinking of sulfhydrl groups which precipitate at the membrane resulting in dark inclusions known as Heinz bodies
30
Why is episodic hemolysis observed in G6PD deficiency?
1) Because hemolysis only occurs in older rbcs
Older cells = decreased enzymes (do not produce)
Younger cells= normal amount of enzymes
31
What autosomal recessive disease results in chronic hemolysis due to a defect in a protein involved with the conversion of phosphoenol pyruvate to pyruvate?
Pyruvate Kinase Deficiency
32
Why does Pyruvate kinase deficiency cause hemolysis?
The absence of the conversion of phosphoenol pyruvate to pyruvate results in a decrease in ATP.
Decreased ATP leads to loss of membrane integrity
33
What are Schistocytes and what are they associated with?
1) Fragmented RBCs due to mechanical trauma
| 2) Associated with Stenotic valve, DIC, TTP/HUS
34
Why do children have skull deformities with chronic untreated anemia and adults do not?
Children already have hematopoeisis going on throughout body so it must expand in the skull. Adults just turn on hematopoeisis within the long bones
35
What are causes of hypochromic microcytic polychrmoasia anemia?
1) Beta Thalassemia
| 2) Treated iron deficiency
36
What is the mutation that causes sickle cell anema (HbS)?
1) Point mutation of the 6th codon in the beta globin 2) Results in replacement of glutamate with valine
37
What is the mutation found in HbC?
1) Point mutation of the 6th codon in the beta globin
2) Results in replacement of glutamate with lysine
3) Increases sickling in sickle cell trait
38
How does the Sickle shape form in Sickle cell anemia?
When HbS becomes deoxygenated it results in polymerization and aggregation that causes the cytoplasm to become viscous. Together these cause a sickle shape
39
What four factors influence sickling of rbcs?
1) Interaction with other hemoglobin
2) Intracellular pH
3) Mean cell hemoglobin concentration
4) Transit time through microvascular beds
40
What determines the severity of chronic hemolysis in Sickle cell anemia?
1) The percentage of irreversibly sickled cells
41
What is the difference in where spherocytes and sickle cells are captured in the spleen?
1) Spherocytes = cords of Billroth
| 2) Sickle cells = cords and sinusoids
42
How does autosplenectomy, a common occurnence in Sickle cell patients, occur?
1) It occurs by chronic erythrostasis that leads to splenic infarction, fibrosis, and progressive shrinkage
43
Clinical features of Sickle cell disease
1) Severe hemolytic anemia
2) Vaso-occlusive (pain) crises - common in bone, brain, liver, lungs, spleen
3) Sequestration crises (in children with intact spleens)- causes massive splenomegally
4) Aplastic crises - occurs with Parvovirus infx
5) Chronic hypoxia- results in impaired growth and development
6) Hyposthenuria (unable to concentrate urine)
7) Increased susceptibility to encapsulated organisms
8) Gall stones
44
What is used to treat Sickle cell anemia and why?
1) Hydroxyurea
2) Inhibits DNA synthesis resulting in an increase in HbF and an anti-inflammatory effect due to a decrease in wbc production
45
What is the cause of ineffective erythropoeisis in beta thalaseemia?
1) The accumulation of alpha globins results in membrane damage causing ineffective erythropoeisis
46
What are the complications of ineffective hematopoiesis for those with severe beta thalassemia?
1) It causes extramedullary hematopoiesis
2) Also leads to increase in absorption of dietary iron leading to iron overload
3) Iron overload complicates blood transfusions
47
What are the two clinical syndromes of beta thalassemia?
1) Beta thalassemia major - requires blood transfusions, generally homozygous, results in severe ineffective hematopoeisis; HbF major
2) Beta thalassemia minor - usually asymptomatic or mild anemia; generally heterozygous; HbA2 major
48
What are the four clinical syndromes of alpha thalassemia?
1) Silent Carrier State (1 deletion)
2) Alpha Thalassemia trait (2 deletions)
3) Hemoglobbin H Disease (3 deletions)
4) Hydrops fetalis (4 deletions)
49
What type of tetramers form in Hemoglobin H disease?
HbH - tetramer of beta globin; high affinity for oxygen; forms with deletion of 3 alpha genes
50
What type of tetramers form in Hydrops fetalis?
Bart's hemoglobin- tetramer of gamma globin; deletion of all four alpha genes
51
What is Hemoglobin SC disease?
It is a combination of HbS and HbC that increases sickling
52
What disease is due to an X linked, acquired, mutation that results in increased complement mediated RBC lysis?
Paroxysmal Nocturnal Hemoglobinuria (PNH)
53
What does phosphatidylinositol glycan complementation group A (PIGA) gene found defective in paroxysmal nocturnal hemoglobinuria encode?
PIGA encodes cell surface proteins for rbcs
1) CD55
2) CD59 (inhibitor of C3 convertase)
3) C8 binding protien
54
What diseases cause spherocytes?
1) Hereditary spherocytosis
2) Immunohemolytic anemia
3) Pyruvate kinase deficiency
4) Anything that causes partial damage to membrane
55
What are the causes of secondary Warm Antibody type of Autoimmune hemolytic anemia?
1) Predispositions (SLE or lymphoid neoplasm)
2) Drug exposure (Antigenic drugs-binds to surface proteins and is identified by Ig or Tolerance breaking drugs- cause creation of Ig against RBC antigen)
56
What are the different types of Autoimmune Hemolytic Anemia?
1) Warm Antibody Type (IgG)- assoc. drugs/predisposition; extravascular hemolysis
think: Warm is GGGGreat!
2) Cold Agglutinin Type (IgM)- assoc. infx (CMV, EBV, Mycoplasma, HIV); Reynauds phenomenon, intravasucar hemolysis
think: Cold ice cream yuMMM!
57
What are the microangiopathic disorders that can cause hemolytic anemia?
1) Disseminated Intravascular Coagulation (DIC)
2) Thrombotic thrombocytopenic purpura (TTP)
3) Hemolytic Uremic Syndrome (HUS)
4) Maligant Hypertension
58
What causes hemolytic uremic syndrome? What is characteristic histology finding?
1) Infection of Enterhemorrhagic E. coli that results in endothelial injury
2) Schistocytes
59
What causes Thrombotic Thrombocytopenic purppura (TTP)?
A dysregulation of vWF (involved with clotting) due to a deficiency in ADAMTS13
60
What two interactions are B12 involved in? What metabolites accumulate in B12 deficiency?
1) Homocysteine --> Methionine (results in THF)
2) Methylmalonyl CoA --> Succinyl CoA
3) Homocysteine and Methylmalonyl
61
How do neurological complications of B12 deficiency occur?
1) Neurological complications are due to an accumulation of abnormal fatty acids
2) Fatty acids accumulate due to the accumulation of methylmalonyl acid that builds up
62
What are the three antibodies observed in Pernicious Anemia?
1) Type I (blocks binding of B12 to intrinsic factor)
2) Type II (blocks binding of intrinsic factor/B12 complex to the ileal receptor)
3) Type III (targets the parietal cells by recognizing the subunits of the gastric protein pumps)
63
What drives Pernicious anemia?
1) Autoimmune attack that is T cell driven on the gastric mucosa
64
What are the clinical findings of a pt. with Pernicious Anemia?
1) Gastric atrophy along with intestinalization (metaplasia parietal to goblet)
2) Glazed and beefy tongue
3) Megaloblastic rbcs
4) Demylation of the lateral and dorsal tracts of the spinal cord (causes sensory ataxia and spastic paraparesis)
65
How do you differentiate megaloblastic anemia caused by folate deficiency or B12 deficiency?
1) Folate = low folate, High homocysteine, normal methylmalonic acid, no neurological problems
2) B12 = low B12, high homocysteine, high methylmalonic acid, neurological problems (ascending and descending demyelination)
66
What are causes of folate deficiency?
1) Inadequate intake
2) Increased requirement (pregnancy, cancer, hemolytic anemia)
3) Impaired utilization (inhibition of enzymes)
67
What are causes of B12 deficiency?
1) Pernicious anemia
2) Ileum resection
3) Absence of pancreatic enzymes
4) Achlorydia
5) Crohn's disease
6) Diphyllobothrium latum (tape worm)
68
What is iron deficiency in adult men and postmenopausal women until proven otherwise?
Chronic blood loss in the gastrointestinal tract
69
What are the causes of iron deficiency?
1) Inadequate amount in diet
2) Impaired absorption
3) Increased requirement (pregnancy)
4) Chronic blood loss
70
What does the bone marrow look like in a pt. with iron deficiency?
When using a prussian stain there is NO evidence of iron present within the macrophages
71
What is Plummer- Vinson syndrome
1) Iron deficiency
2) Esophageal webs
3) Glossitis
72
What are specific causes of aplastic anemia?
1) Idiopathic
2) Chemical agents (alkylating, antimetabolite, benzene, chloramphenicol)
3) Whole body irradiation
4) Viral infection (CMV, HIV, EBV, Herpes Zoster)
5) Inherited (Fanconi anemia and telomerase defects)
73
What is the difference between relative and absolute polycythemia?
1) Relative - decreased plasma volume, increased hemoconcentration
2) Absolute - increase of red cell mass
74
What is the cause of a myelophthisic anemia?
Bone occupying lesions due to metastatic cancer, granulomatous disease, or myeloproliferative disease.
75
What are causes of relative polycythemia?
1) Dehydration
| 2) Gaisbock (stress) syndrome - obese, anxious, hypertensive
76
What are causes of absolute polycythemia?
1) Primary - intrinsic defect in the hematopoietic precursors
2) Secondary - response to increased levels of erythropoeitin
77
Causes of absolute secondary polycythemia?
1) Compensatory response to lung dx., high altitude
2) Paraneoplastic
3) Hemoglobinopathies
4) Inherited defects that stabilize HIF-1alplha
78
What cytokine is associated with anemia of chronic disease? What does it result in?
1) IL-6
2) Increased Hepcidin --> decreased Ferroportin
3) Decreased Ferroportin results in Iron remaining in macrophages and intestinal wall cells
4) Low erythropoeitin due to high Hepcidin
79
What are the causes of anemia of chronic disease?
1) Chronic infection (osteomyelitis, neoplasm, chronic immune disorder)
2) Neoplasm
3) Chronic immune disorder
80
What is hypersplenism and why does it occur?
1) Syndrome that produces anemia, thrombocytopenia, and leukopenia alone or in combination
2) Splenomegaly causing prolonged exposure of components to macrophages in the spleen
81
What are causes of congestive splenomegally? (3 total)
1) Intrahepatic disorders (cirrhosis, shistosomiasis)
2) Systemic venous congestion (right heart failure)
3) Obstruction of the extrahepatic/splenic veins (tumors)
82
What are factors that predispose spleens to rupture?
1) Malaria
2) Infectious mononucleosis
3) Typhoid fever
4) Lymphoid neoplasms
83
What causes dacryocytes?
1) Dacryocytes = tear drop shaped cells
| 2) Primary myelofibrosis
84
What are the general causes of microcytic anemia? What are the 4 causes?
1) Decreased iron and decreased globin
| 2) Iron deficiency, sideroblastic anemia, thalassemia, and anemia of chronic disease
85
What are the phases of iron deficiency?
1) Decreased storage (low Ferritin/High Total Iron Binding capacity = increased transferrin)
2) Decreased serum (low serum iron and low transferrin saturation)
3) normocytic anemia
4) microcytic, hypochromic anemia
86
Bite cells
G6PD deficiency (x linked)
87
Ringed sideroblasts
1) Siderolbastic anemia
| 2) Excess iron in mitochondria
88
Absent beta chain
Beta thalasemia major
89
What is commonly observed as a complication to beta thalassemia major?
1) Secondary hemochromatosis due to chronic requirement of blood transfusions
90
Pt. presents with lines on gingivae and on long bones via xray; encephalopathy; erythrocyte basophilic stippling; abdominal colic, Wrist and foot drop
Lead poisoning
91
Tx for lead poisoning
Dimercapol and EDTA
92
Defect in heme sythesis due to defect in ALA synthase or reversible causes such as alcohol, lead and isoniazid
Sideroblastic anemia
93
What causes reversible sideroblastic anema?
1) Lead
2) Alcohol
3) INH (causing B6 deficiency)
94
What are iron study findings for sideroblastic anemia?
1) Increased Iron
2) Normal TIBC
3) Increased ferritin
95
Defect in UMP synthase that results in megaloblastic anema as well as increased orotic acid
Orotic aciduria
96
How do you differentiate OTC deficiency from orotic aciduria?
OTC has hyperammonemia; orotic aciduria does not
97
What would iron studies for a pt. with anemia of chronic disease come back as?
1) Decreased Iron, Decreased TIBC, Increased Ferritin
98
Normocytic hemolytic intrinsic causes
1) Hereditary spherocytosis (extravascular hemolysis)
2) G6PD deficiency (extravascular hemolysis)
3) Pyruvate kinase (Extravascular hemolysis)
4) Paroxysmal nocturnal hemoglobinuria
5) HbC disease
6) Sickle cell diseae
99
Glutamate --> valine in position 6 of Beta globulin gene
Sickle cell
100
Glutamate --> Lysine in position 6 of beta globulin gene
HbC
101
Normocytic hemolytic extrinsic causes
1) Autoimmune
2) Microangiopathic (TPP, DIC, HUS, SLE, malignant HTN)
3) Macroangiopathic (valve or aortic stenosis)
102
What is a direct coombs test? indirect?
1) Direct = anti-Ig antibody added to pt. blood; RBCs agglutinate if covered with Ig
2) Indirect = normal RBCs are added to pt. blood;
103
What is the cause of acute intermittent porphyria and what substrate builds up?
1) Defective porphobilinogen deaminase
| 2) Porphobilinogen
104
Pt. presents with painful abdomen, red urine, polyneuropathy, psychological disturbances and may have been precipitated by drugs
Acute intermittent porphyria
105
Defect in porphobilinogen deaminase
acute intermittent porphyria
106
What is the cause of porphyria cutanea tarda and what substrate builds up?
1) Uroporphyrinogen decarboxylase
| 2) Urophorphyrin
107
Pt. presents with blistering cutaneous photosensitivity, tea colored urine. Most common porphyria
Porphyria cutanea tarda
108
Defect in uroporphryinogen decarboxylase
Porphyria cutanea tarda
109
What is the inheritance pattern of sickle cell anema
autosomal recessive
110
What is the serum protein that binds to free hemoglobin and promotes its uptake in the reticuloendothelial system found in an intravascular hemolysis?
Haptoglobin
111
What is the result of a transfer of glutamate to valine in the 6th position of chromosome 11? What does this amino acid substitution result in?
1) Sickle cell anemia
2) Results in a not charged valine increasing the aggregation of heme in an deoxygenated state due to the beta chain fitting into an alpha chain of another hemoglobin
112
What is the reticulocyte index in a pt. whose bone marrow is responding to excessive RBC destruction
2%
113
What is the cause of intravascular hemolysis due to a transfusion? extravascular?
1) ABO (very severe)
| 2) Minor antigen ( less severe and has a delayed response)
114
What must you check in order to determine a hemolytic anemia?
1) Haptoglobin
2) LDH
3) Bilirubin levels
115
What are the causes of normocytic anemia?
1) Renal disease (decreased erythropoetin)
2) Aplastic anemia
3) Bone marrow fibrosis
4) Tumor
5) Anemia of chronic disease
116
Elderly with anemia: you should think...
Colon cancer
117
What should be given with an oral dose of iron?
Vitamin C (orange juice, ect)
118
What does the RDW measure?
1) Measures the variation in RBC size
119
What you observe in electrophoresis of a thalassemia?
General decrease in all proteins (due to alpha globin's importance in all forms of heme)
120
What is the genotype of Cooley's anemia?
1) Homozygous mutation of beta globin gene on chromosome 11
121
What pop. is assoc. with Cooley's anemia?
Mediterranean
122
What does skull Xray with "Crew cut" appearance indicate with a microcytic anemia?
Cooley's anemia
123
How is thalssemia treated and what are the complications of this treatment?
1) Blood transfusions to replete hemoglobin
| 2) Secondary hemochromotosis leading to CHF
124
What drug is used along with transfusions for thalassemia pt.?
Desferrioxamine (chelating agent that eliminates excess iron)
125
What symptoms should you look for in a pt. with aplastic anemia?
1) Fatigue, pallor
| 2) Easy bruising and petechiae
126
What are the extrinsic causes of hemolyitc anemia?
1) Mechanical stress
2) Drugs
3) Autoimmune
127
What are the intrinsic causes of hemolytic anemia?
Think: what does an rbc consist of... membrane, hemoglobin, and enzymes
1) Sickle cell
2) Hb H disease
3) Hereditary Spherocytosis
4) Paroxysmal nocturnal hemoglobinuria
5) G6PD deficiency
6) Pyruvate kinase deficiency
128
What is required for diagnosis of sickle cell disease, beside presence of anemia and peripheral smear?
1) Need hemoglobin electrophoresis
129
How do you treat a pt. with sickle cell anema?
1) Advise staying away from elevation, dehydration, and treating infections quickly
130
What is the best treatment for hereditary spherocytosis?
1) Splenectomy
| 2) Prophylactic treatments to prevent infection by encapsulated organisms
131
What drugs induce hemolysis in pt. with G6PD deficiency
think: hemolysis IS PAIN
1) INH
2) Sulfa drugs
3) Primaquine
4) Aspirin
5) Ibuprofen
6) Nitrofuratoin
132
What is used to treat paroxysmal nocturnal hemoglobinuria?
1) Glucocorticosteroids
| 2) Bone marrow transplant
