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pathology > Red Blood Cell Disorders > Flashcards

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
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2
Q

Stimuli that repress O2 release?

A

Increased oxygen content; PV

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3
Q

Extra renal sources of EPO?

A

RCC and HCC ectopically

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4
Q

How is corrected reticulocyte count measured?

A

Actual HCT/45* reticulocyte count

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5
Q

> 3% corrected erythropoiesis as an indicator?

A

Good bone marrow response to anaemia; effective erythropoiesis

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6
Q

Reticulocyte count correction for polychromasia?

A

Original correction/2

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7
Q

Sites for EMH?

A

Liver, spleen

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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

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9
Q

Hematopoiesis sites in fetus?

A

Yolk sac–> liver–> bone marrow in 5th/6th month of gestation

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10
Q

Parameters decreased in anaemia?

A

Hb, Hct, RBC concentration

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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

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12
Q

Conditions with increased vs. decreased MCHC?

A

Decreased->microcytic anaemia

Increased->spherocytosis

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13
Q

Increased RDW?

A

Iron deficiency anaemia

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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

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15
Q

Primary pathway of ATP production in RBCs?

A

Anaerobic glycolysis->lactic acid->to liver converted to glucose via gluconeogenesis

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16
Q

Function of Cori cycle?

A

Glucose from liver derived from lactic acid produced by RBC–>to RBC–>synthesis of ATP

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17
Q

Function of pentose phosphate pathway by RBCs?

A

Synthesizes glutathione

GSH converts H2O2 to H2O[prevents destruction] ; neutralises acetaminophen free radicals

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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

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19
Q

Function of luebering-rapoport pathway used by mature RBCs?

A

Synthesizes 2,3 BPG–> shifts OBC to right–>release of oxygen

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20
Q

Normal lifespan of RBCs?

A

110-120 days in peripheral blood

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21
Q

How are platelets formed?

A

Stem cell–>pluripotent cells–>myeloid progenitor–>megakaryocyte–>cytoplasmic budding from megakaryocyte

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22
Q

Which blood components have HLA antigens?

A

Platelets and RBCs

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23
Q

Ferritin vs. hemosiderin?

A

Ferritin-soluble iron-binding storage protein

Hemosiderin-insoluble degradation product of ferritin in lysosomes

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24
Q

Synthesis of ferritin?

A

Bone marrow macrophages/hepatocytes

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25
Q

Decrease in serum ferritin?

A

Iron deficiency anaemia

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26
Q

Increase in serum ferritin?

A

ACD- increased IL-6 during inflammation stimulates ferritin production
Iron overload disease

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27
Q

Conditions with decreased serum iron?

A

Iron deficiency

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28
Q

Conditions with increased serum iron?

A

Iron overload diseases-sideroblastic anaemia and hemochromatosis

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29
Q

Serum iron vs. serum total iron binding capacity vs. iron saturation?

A

Serum iron-iron bound to transferrin

TIBC-concentration of transferrin

Iron saturation-% of binding sites on transferrin occupied by iron

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30
Q

Measure iron saturation? And normal values?

A

= serum iron/TIBC* 100

33%

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31
Q

Types of normal haemoglobin detected on Hb electrophoresis?

A

HbA=97%
HbA2=2%
HbF=1%

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32
Q

Source of transferrin iron?

A

Macrophage and duodenum

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33
Q

Why does achlorhydria decrease availability of iron for absorption?

A

Gastric acid frees elemental iron from heme and non heme products

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34
Q

Absorption of iron from a plant source vs. meat?

A

Plant source: Fe3+ cannot be absorbed directly; meat: Fe2+ can be absorbed directly into duodenum

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35
Q

Mechanism of regulation of iron absorption?

A

Iron bound to transferrin–> HFE protein product + transferrin receptors differentiate sensor cells into mature enterocytes

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36
Q

Name the master iron regulatory hormone?

A

Hepicidin

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37
Q

How does Hepicidin regulate absorption and release of iron?

A

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

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38
Q

Hepicidin is decreased in which conditions?

A

Normal menstrual cycle
Pregnancy and lactation
Any anaemia

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39
Q

Factor required for production of RBC in BM?

A

EPO synthesised in renal cortex by interstitial cells of peritubular capillary bed

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40
Q

Most common cause of iron deficiency anaemia in adult male?

A

PUD–>blood loss

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41
Q

MCC of iron deficiency anaemia in females

A

Pregnancy and lactation–>increased utilisation

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42
Q

MCC of iron deficiency anaemia in children?

A

Decreased intake

43
Q

MCC of iron deficiency anaemia in elderly?

A

Colon cancer/polyps–>blood loss

44
Q

Which parasitic infestation causes iron deficiency anaemia?

A

Hookworm infestation

45
Q

Clinical findings in chronic iron deficiency anaemia?

A 
1.Esophageal web [Plummer-Vinson syndrome]- dysphasia for solids not
Liquids 
2. Achlorhydria
3. Glossitis and angular cheilosis 
4. Koilonychia
46
Q

Anaemia with MCV>100micronm3

A

Megaloblastic anaemia= folic acid deficiency and B12 deficiency

Non megaloblastic anaemia

47
Q

Aetiology of anaemia in chronic diseases?

A
  1. Chronic inflammation- RA, TB, Crohn’s disease
  2. Malignancy
  3. alcoholism
48
Q

Type of inheritance in thalassemia?

A

Autosomal recessive disorders

49
Q

Geographical predisposition to alpha thalassemia vs. beta thalassemia?

A

Alpha- southeast Asians and blacks

Beta-Greeks, blacks and Italians

50
Q

Pathogenesis of alpha thalassemia vs. beta thalassemia?

A

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
Q

Depending on # of genes deleted classify alpha thalassemia?

A

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
Q

Hb electrophoresis detects which alpha thalassemia?

A

HbH and Hb Bart

53
Q

Specific findings in peripheral blood smear in beta thal minor?

A

Target cells and teardrop cells [damage to RBC membrane from removal of excess globin chains by macrophages]

54
Q

Hb electrophoresis findings in Beta thalassemia minor?

A

HbA decreased, HbA2 and HbF increased

55
Q

Specific peripheral blood smear findings in beta thalassemia major?

A

Howell jolly bodies, reticulocytes, tear drop cells, nucleated cells

Increased RDW

56
Q

Findings in Hb electrophoresis in beta thalassemia major?

A

No synthesis of HbA, increased HbA2 and HbF

57
Q

Features of extramedullary hematopoiesis?

A

Hepatosplenomegaly; hair on end appearance of skull x Ray due to expansion of bone marrow

58
Q

Aetiology of sideroblastic anaemia?

A

Chronic alcoholism
B6 deficiency
X linked recessive
Lead poisoning

59
Q

Why are ringed sideroblasts present in sideroblastic anaemia?

A

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
Q

Mechanism of sideroblastic anaemia development in chronic alcoholism?

A

Alcohol is a mitochondrial toxin–>damages heme bio synthetic pathway

61
Q

Mechanism of sideroblastic anaemia in pyridoxine deficiency?

A

Cofactor for aminolevulinic synthase

[INH therapy->pyridoxine deficiency]

62
Q

Sources of lead poisoning?

A

Pica for lead based paints, pottery glazes, battery/ammunition factory, radiator repair mechanics, jewellery, plumbing, toys

Maggi ;)

63
Q

Mechanism of sideroblastic anaemia in lead poisoning?

A

Denatures enzymes;

  1. Ferrochelatase-Fe cannot bind with protoporphyrin
  2. ALA dehydrase
  3. Ribonuclease
64
Q

Mechanism of coarse basophilic stippling in sideroblastic anaemia due to lead poisoning?

A

Ribosomes cannot be degraded and persist in RBC due to denaturation of ribonuclease

65
Q

Clinical findings in lead poisoning?

A

Encephalopathy-cerebral edema & papilledema
Growth retardation-children
Peripheral neuropathy-adults
Nephrotoxic damage

66
Q

Best confirmatory test for lead poisoning?

A

Whole blood and urine lead levels

67
Q

Specific syndrome caused by tubular damage due to lead?

A

Fanconi syndrome–> Proximal renal tubular acidosis; phosphaturia; aminoaciduria; glucosuria

68
Q

Factor required for absorption of B12?

A

IF from parietal cell

69
Q

Mechanism of removal of B12 from food?

A

Parietal gastric cells–>HCL–>pepsin activation–>free B12

70
Q

Mechanism of protection of free B12 from acid in stomach?

A

R binders bind to B12 [R binders from salivary glands]

71
Q

Site of absorption of B12 in intestine?

A

Ileum

72
Q

B12 stores in the liver last for how long?

A

6-9 year supply

73
Q

Most common cause of B12 deficiency?

A

Pernicious anaemia–> autoimmune destruction of parietal cells

74
Q

Parasitic infestation that leads to B12 deficiency?

A

Fish tapeworm-absorb >80% of b12

75
Q

Antibodies formed that are specific to PA?

A

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
Q

Associated diseases with PA?

A

H. Pylori;

Other autoimmune diseases-DM, graves and Addison

77
Q

Clinical findings with B12 deficiency?

A

Glossitis

Neurological diseases

78
Q

Neurological symptoms characteristic of B12 deficiency?

A
  1. Peripheral neuropathy with sensorimotor dysfunction
  2. Demyelination of spinal cord-posterior column, lateral corticospinal and dorsal spinocerebellar
  3. Dementia
79
Q

Mechanism of neurological deficits in B12 deficiency?

A

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
Q

Specific findings in peripheral blood smear of B12 deficiency?

A

Pancytopenia, oval macrocytes and hyper segmented neutrophils

81
Q

Specific bone marrow aspiration findings in B12 deficiency anaemia?

A

Megaloblastic nucleated cells with open chromatin

82
Q

Specific test (outdated) for B12 deficiency?

A

Schilling test

83
Q

Specific lab findings in serum in B12 deficiency?

A

Increased homocysteine, methylmalonic acid and decreased B12

84
Q

Specific lab findings in folic acid deficiency?

A

RBC folic acid and serum folic acid decreased

85
Q

Form of folic acid present in plant and animal proteins?

A

Polyglutamate

86
Q

Mechanism of folic acid deficiency with phenytoin?

A

Inhibits intestinal conjugase that converts Polyglutamate to mono glutamate in intestine

87
Q

Form of folic acid absorbed in jejunum?

A

Mono glutamate

88
Q

Mechanism of folic acid deficiency with alcohol and OCPs?

A

Block absorption of mono glutamate

89
Q

Stores of folic acid in liver last for?

A

3-4 months

90
Q

Mechanism of folic acid deficiency with methotrexate/trimethoprim-sulfamethoxazole?

A

Inhibit dihydrofolate reductase

91
Q

Mechanism of folic acid deficiency with 5-fluorouracil?

A

Inhibits thymidylate synthase

92
Q

Mechanism of delayed nuclear maturation vs. normal cytoplasmic maturation in megaloblastic anaemia?

A

Impaired DNA synthesis->blocks cell division in rapidly dividing cells–>large nucleated hematopoietic cells with open chromatin

Normal RNA and protein synthesis

93
Q

Most common cause of elevated homocysteine levels [atherogenic factor]?

A

Folic acid deficiency

94
Q

Clinical findings with B12 deficiency?

A

Glossitis

Neurological diseases

95
Q

Neurological symptoms characteristic of B12 deficiency?

A
  1. Peripheral neuropathy with sensorimotor dysfunction
  2. Demyelination of spinal cord-posterior column, lateral corticospinal and dorsal spinocerebellar
  3. Dementia
96
Q

Specific findings in peripheral blood smear of B12 deficiency?

A

Pancytopenia, oval macrocytes and hyper segmented neutrophils

97
Q

Specific bone marrow aspiration findings in B12 deficiency anaemia?

A

Megaloblastic nucleated cells with open chromatin

98
Q

Specific test (outdated) for B12 deficiency?

A

Schilling test

99
Q

Specific lab findings in serum in B12 deficiency?

A

Increased homocysteine, methylmalonic acid and decreased B12

100
Q

Specific lab findings in folic acid deficiency?

A

RBC folic acid and serum folic acid decreased

101
Q

Form of folic acid absorbed in jejunum?

A

Mono glutamate

102
Q

Mechanism of folic acid deficiency with alcohol and OCPs?

A

Block absorption of mono glutamate

103
Q

Stores of folic acid in liver last for?

A

3-4 months

pathology (6 decks)

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