Red Blood Cell Disorders Flashcards
1
Q
Stimuli for EPO release?
A
Hypoxemia; severe anaemia; high altitude; decreased O2 saturation; left shifted O2 binding curve
2
Q
Stimuli that repress O2 release?
A
Increased oxygen content; PV
3
Q
Extra renal sources of EPO?
A
RCC and HCC ectopically
4
Q
How is corrected reticulocyte count measured?
A
Actual HCT/45* reticulocyte count
5
Q
> 3% corrected erythropoiesis as an indicator?
A
Good bone marrow response to anaemia; effective erythropoiesis
6
Q
Reticulocyte count correction for polychromasia?
A
Original correction/2
7
Q
Sites for EMH?
A
Liver, spleen
8
Q
Conditions wherein EMH occurs?
A
Intrinsic bone marrow disease- myelofibrosis
Accelerated erythropoiesis-expansion of bone marrow cavity-sickle cell anaemia, thalassemia beta major
9
Q
Hematopoiesis sites in fetus?
A
Yolk sac–> liver–> bone marrow in 5th/6th month of gestation
10
Q
Parameters decreased in anaemia?
A
Hb, Hct, RBC concentration
11
Q
General clinical findings in anaemia?
A
Pallor of skin, conjunctiva, palmar creases;
Pulmonary valve flow murmur;
Fatigue, dyspnea with exertion;
High output cardiac failure->decreased viscosity
12
Q
Conditions with increased vs. decreased MCHC?
A
Decreased->microcytic anaemia
Increased->spherocytosis
13
Q
Increased RDW?
A
Iron deficiency anaemia
14
Q
No citric acid cycle/beta oxidation of fatty acids/production of ketone bodies due to lack of which organelle in mature RBC?
A
Mitochondria;
Also lack nucleus
15
Q
Primary pathway of ATP production in RBCs?
A
Anaerobic glycolysis->lactic acid->to liver converted to glucose via gluconeogenesis
16
Q
Function of Cori cycle?
A
Glucose from liver derived from lactic acid produced by RBC–>to RBC–>synthesis of ATP
17
Q
Function of pentose phosphate pathway by RBCs?
A
Synthesizes glutathione
GSH converts H2O2 to H2O[prevents destruction] ; neutralises acetaminophen free radicals
18
Q
Function of methemoglobin reductase pathway in mature RBC?
A
Heme iron is in ferric form cannot bond to O2;
Reductase system converts it back to ferrous form
19
Q
Function of luebering-rapoport pathway used by mature RBCs?
A
Synthesizes 2,3 BPG–> shifts OBC to right–>release of oxygen
20
Q
Normal lifespan of RBCs?
A
110-120 days in peripheral blood
21
Q
How are platelets formed?
A
Stem cell–>pluripotent cells–>myeloid progenitor–>megakaryocyte–>cytoplasmic budding from megakaryocyte
22
Q
Which blood components have HLA antigens?
A
Platelets and RBCs
23
Q
Ferritin vs. hemosiderin?
A
Ferritin-soluble iron-binding storage protein
Hemosiderin-insoluble degradation product of ferritin in lysosomes
24
Q
Synthesis of ferritin?
A
Bone marrow macrophages/hepatocytes
25
Decrease in serum ferritin?
Iron deficiency anaemia
26
Increase in serum ferritin?
ACD- increased IL-6 during inflammation stimulates ferritin production
Iron overload disease
27
Conditions with decreased serum iron?
Iron deficiency
28
Conditions with increased serum iron?
Iron overload diseases-sideroblastic anaemia and hemochromatosis
29
Serum iron vs. serum total iron binding capacity vs. iron saturation?
Serum iron-iron bound to transferrin
TIBC-concentration of transferrin
Iron saturation-% of binding sites on transferrin occupied by iron
30
Measure iron saturation? And normal values?
= serum iron/TIBC* 100
33%
31
Types of normal haemoglobin detected on Hb electrophoresis?
HbA=97%
HbA2=2%
HbF=1%
32
Source of transferrin iron?
Macrophage and duodenum
33
Why does achlorhydria decrease availability of iron for absorption?
Gastric acid frees elemental iron from heme and non heme products
34
Absorption of iron from a plant source vs. meat?
Plant source: Fe3+ cannot be absorbed directly; meat: Fe2+ can be absorbed directly into duodenum
35
Mechanism of regulation of iron absorption?
Iron bound to transferrin--> HFE protein product + transferrin receptors differentiate sensor cells into mature enterocytes
36
Name the master iron regulatory hormone?
Hepicidin
37
How does Hepicidin regulate absorption and release of iron?
Increased transferrin bound iron->increased HFE->increased Hepicidin->decreases absorption of iron and release of iron from bone macrophages
Decreased transferrin bound iron-> decreased Hepicidin
38
Hepicidin is decreased in which conditions?
Normal menstrual cycle
Pregnancy and lactation
Any anaemia
39
Factor required for production of RBC in BM?
EPO synthesised in renal cortex by interstitial cells of peritubular capillary bed
40
Most common cause of iron deficiency anaemia in adult male?
PUD-->blood loss
41
MCC of iron deficiency anaemia in females
Pregnancy and lactation-->increased utilisation
42
MCC of iron deficiency anaemia in children?
Decreased intake
43
MCC of iron deficiency anaemia in elderly?
Colon cancer/polyps-->blood loss
44
Which parasitic infestation causes iron deficiency anaemia?
Hookworm infestation
45
Clinical findings in chronic iron deficiency anaemia?
```
1.Esophageal web [Plummer-Vinson syndrome]- dysphasia for solids not
Liquids
2. Achlorhydria
3. Glossitis and angular cheilosis
4. Koilonychia
```
46
Anaemia with MCV>100micronm3
Megaloblastic anaemia= folic acid deficiency and B12 deficiency
Non megaloblastic anaemia
47
Aetiology of anaemia in chronic diseases?
1. Chronic inflammation- RA, TB, Crohn's disease
2. Malignancy
3. alcoholism
48
Type of inheritance in thalassemia?
Autosomal recessive disorders
49
Geographical predisposition to alpha thalassemia vs. beta thalassemia?
Alpha- southeast Asians and blacks
Beta-Greeks, blacks and Italians
50
Pathogenesis of alpha thalassemia vs. beta thalassemia?
Alpha thalassemia-Gene deletions-4 genes control alpha chain
Beta thalassemia- splicing defect/nonsense mutation with formation of stop codon->premature termination of beta globin chain synthesis
51
Depending on # of genes deleted classify alpha thalassemia?
Silent carrier-1
Alpha thalassemia trait-2 [mild anaemia]
HbH-3 [severe haemolytic anaemia due to phagocytosis of beta inclusions in RBCs]
Hb Bart-4 [incompatible with life]
52
Hb electrophoresis detects which alpha thalassemia?
HbH and Hb Bart
53
Specific findings in peripheral blood smear in beta thal minor?
Target cells and teardrop cells [damage to RBC membrane from removal of excess globin chains by macrophages]
54
Hb electrophoresis findings in Beta thalassemia minor?
HbA decreased, HbA2 and HbF increased
55
Specific peripheral blood smear findings in beta thalassemia major?
Howell jolly bodies, reticulocytes, tear drop cells, nucleated cells
Increased RDW
56
Findings in Hb electrophoresis in beta thalassemia major?
No synthesis of HbA, increased HbA2 and HbF
57
Features of extramedullary hematopoiesis?
Hepatosplenomegaly; hair on end appearance of skull x Ray due to expansion of bone marrow
58
Aetiology of sideroblastic anaemia?
Chronic alcoholism
B6 deficiency
X linked recessive
Lead poisoning
59
Why are ringed sideroblasts present in sideroblastic anaemia?
Sideroblastic anaemia- defect in heme synthesis in mitochondria of developing RBCs
[BM ASPIRATE]
Defective Heme-->negative feedback on delta-aminolevulinic acid synthase blocked-->iron accumulates in mitochondria-->ringed sideroblasts
60
Mechanism of sideroblastic anaemia development in chronic alcoholism?
Alcohol is a mitochondrial toxin-->damages heme bio synthetic pathway
61
Mechanism of sideroblastic anaemia in pyridoxine deficiency?
Cofactor for aminolevulinic synthase
[INH therapy->pyridoxine deficiency]
62
Sources of lead poisoning?
Pica for lead based paints, pottery glazes, battery/ammunition factory, radiator repair mechanics, jewellery, plumbing, toys
Maggi ;)
63
Mechanism of sideroblastic anaemia in lead poisoning?
Denatures enzymes;
1. Ferrochelatase-Fe cannot bind with protoporphyrin
2. ALA dehydrase
3. Ribonuclease
64
Mechanism of coarse basophilic stippling in sideroblastic anaemia due to lead poisoning?
Ribosomes cannot be degraded and persist in RBC due to denaturation of ribonuclease
65
Clinical findings in lead poisoning?
Encephalopathy-cerebral edema & papilledema
Growth retardation-children
Peripheral neuropathy-adults
Nephrotoxic damage
66
Best confirmatory test for lead poisoning?
Whole blood and urine lead levels
67
Specific syndrome caused by tubular damage due to lead?
Fanconi syndrome--> Proximal renal tubular acidosis; phosphaturia; aminoaciduria; glucosuria
68
Factor required for absorption of B12?
IF from parietal cell
69
Mechanism of removal of B12 from food?
Parietal gastric cells-->HCL-->pepsin activation-->free B12
70
Mechanism of protection of free B12 from acid in stomach?
R binders bind to B12 [R binders from salivary glands]
71
Site of absorption of B12 in intestine?
Ileum
72
B12 stores in the liver last for how long?
6-9 year supply
73
Most common cause of B12 deficiency?
Pernicious anaemia--> autoimmune destruction of parietal cells
74
Parasitic infestation that leads to B12 deficiency?
Fish tapeworm-absorb >80% of b12
75
Antibodies formed that are specific to PA?
Antibodies directed against proton pump in parietal cells;
Antibodies that block binding of B12 to intrinsic factor;
Antibodies that block absorption of IF-B12 in ileum
76
Associated diseases with PA?
H. Pylori;
| Other autoimmune diseases-DM, graves and Addison
77
Clinical findings with B12 deficiency?
Glossitis
| Neurological diseases
78
Neurological symptoms characteristic of B12 deficiency?
1. Peripheral neuropathy with sensorimotor dysfunction
2. Demyelination of spinal cord-posterior column, lateral corticospinal and dorsal spinocerebellar
3. Dementia
79
Mechanism of neurological deficits in B12 deficiency?
B12 is a cofactor in conversion of methylmalonyl CoA to succinyl CoA;
B12 deficiency--> increased methylmalonyl CoA and propionyl CoA-->propionyl CoA replaces acetylene CoA in neuronal mem-->demyelination
80
Specific findings in peripheral blood smear of B12 deficiency?
Pancytopenia, oval macrocytes and hyper segmented neutrophils
81
Specific bone marrow aspiration findings in B12 deficiency anaemia?
Megaloblastic nucleated cells with open chromatin
82
Specific test (outdated) for B12 deficiency?
Schilling test
83
Specific lab findings in serum in B12 deficiency?
Increased homocysteine, methylmalonic acid and decreased B12
84
Specific lab findings in folic acid deficiency?
RBC folic acid and serum folic acid decreased
85
Form of folic acid present in plant and animal proteins?
Polyglutamate
86
Mechanism of folic acid deficiency with phenytoin?
Inhibits intestinal conjugase that converts Polyglutamate to mono glutamate in intestine
87
Form of folic acid absorbed in jejunum?
Mono glutamate
88
Mechanism of folic acid deficiency with alcohol and OCPs?
Block absorption of mono glutamate
89
Stores of folic acid in liver last for?
3-4 months
90
Mechanism of folic acid deficiency with methotrexate/trimethoprim-sulfamethoxazole?
Inhibit dihydrofolate reductase
91
Mechanism of folic acid deficiency with 5-fluorouracil?
Inhibits thymidylate synthase
92
Mechanism of delayed nuclear maturation vs. normal cytoplasmic maturation in megaloblastic anaemia?
Impaired DNA synthesis->blocks cell division in rapidly dividing cells-->large nucleated hematopoietic cells with open chromatin
Normal RNA and protein synthesis
93
Most common cause of elevated homocysteine levels [atherogenic factor]?
Folic acid deficiency
94
Clinical findings with B12 deficiency?
Glossitis
| Neurological diseases
95
Neurological symptoms characteristic of B12 deficiency?
1. Peripheral neuropathy with sensorimotor dysfunction
2. Demyelination of spinal cord-posterior column, lateral corticospinal and dorsal spinocerebellar
3. Dementia
96
Specific findings in peripheral blood smear of B12 deficiency?
Pancytopenia, oval macrocytes and hyper segmented neutrophils
97
Specific bone marrow aspiration findings in B12 deficiency anaemia?
Megaloblastic nucleated cells with open chromatin
98
Specific test (outdated) for B12 deficiency?
Schilling test
99
Specific lab findings in serum in B12 deficiency?
Increased homocysteine, methylmalonic acid and decreased B12
100
Specific lab findings in folic acid deficiency?
RBC folic acid and serum folic acid decreased
101
Form of folic acid absorbed in jejunum?
Mono glutamate
102
Mechanism of folic acid deficiency with alcohol and OCPs?
Block absorption of mono glutamate
103
Stores of folic acid in liver last for?
3-4 months
