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Pathology > Chapter 14 - RBCs and Bleeding Disorders > Flashcards

Chapter 14 - RBCs and Bleeding Disorders Flashcards

1
Q

Normal development of Blood cells from utero to maturity?

A

4th month - hematopoiesis begins

Birth - all of the marrow in the skeleton is active (red marrow)

18 years old - active marrow only in vertebrae, ribs, sternum, skull, pelvis, and the proximal epiphyseal regions of the humerus and femur

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2
Q

Common origin of all cells?

What does it give rise to?

A

Pluripotent hematopoietic stem cell

Gives rise to 2 progenitors: the lymphoid and myeloid stem cells

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3
Q

What do the lymphoid and myeloid stem cells give rise to?

A

hmm.. easier with a picture. take what you wnat from itttt :-P

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4
Q

Review of red cell indicies:

Mean corpuscular (cell) volume (MCV)?

Hb?

Mean corpuscular Hemoglobin (MCH)?

MCH concentration (MCHC)?

Red cell distribution widtch (RDW)?

A

MCV = measures RBC size; most important for classification of anemia

Hb = most useful measure of O2 carrying capacity (+HcT)

MCH = avg mass of Hb in an individual RBC

MCHC = Measure of the [Hb] in cells

RDW = provides a measure of the anisocytosis (variation in RBC size)

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5
Q

3 classifications of anemias?

A
  • Blood loss
    • From acute (trauma) or chronic (GI lesion) bleeding
  • Increased rate of destruction
    • Intrinsic (hereditary/acquired)
    • Extrinsic (Ab-mediated/mechanical/infection/chemical)
  • Impaired production
    • Stemm cell issue/reduced Hb synthesis
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6
Q

Common clinical manifestations?

A

Pallor of skin/mucosa (hypotension, weakness, dyspnea on exertion)

Anoxia may cause fatty change in the liver, myocardium, and kidney

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7
Q

In anemia of blood loss (acute) what can happen if bleeding is internal?

Immediately after recovery of blood loss what occurs?

A

Iron in Hb can be recovered

Leukocytosis: from mobilization of granulocytes from storage

Thombocytosis: from increased platelet production

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8
Q

Major common features of Hemolytic anermias?

A
  • Shortened RBC life span
  • Elevated EPO
    • Extramedullary hematopoesis in liver/spleen/nodes
  • Accumulation of Hb catabolic products
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9
Q

What can cause intravascular hemolysis in hemolytic anemias?

A
  • Mechanical injury
    • From defective valves
    • Thrombi in microcirculation
  • Ab/Complement-mediated lysis
  • Infection
    • Malaria
  • Toxins
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10
Q

Clinical findins of intravascular hemolysis?

A
  • Hemoglobinemia/Hemoglobinuria
  • Jaundice
  • Hemosiderinuria
  • Decreased free haptoglobin in the serum
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11
Q

Where does extravascular (most common) hemolysis occur?

When does extravascular hemolysis occur?

A

Occurs within the mononuclear phagocyte system (in spleen)

It occurs when RBCs are:

Tagged for removal (normal) or

Have reduced deformability (sequestration in the spleen - can cause splenomegaly)

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12
Q

What is hereditary spherocytosis?

A

The most common HA resulting from a red cell membrane defect inherited mostly AD.

The deficiency is in membrane-associated skeletal proteins (spectrin/ankyrin) necessary to stabilize the PM

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13
Q

2 types and causes of crisis in hereditary spherocytosis?

A

Aplastic crisis: Parvovirus (kills RBC progenitors)

Hemolytic crisis: EBV mono (increased splenic congestion)

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14
Q

Most common enzymatic disorder of RBCs associated with HA?

A

G6P dehydrogenase deficiency

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15
Q

What occurs with G6PD deficiency?

Inheritance?

A

Reduced ability of RBCs to eliminate toxic oxidants –> increased hemolysis. Most commonly from a failure to convert oxidized glutathione to reduced glutathione

X-linked recessive

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16
Q

In G6PD deficiency when does RBC hemolysis occur?

A

Occurs after exposure to oxidant stress associated with:

Certain drugs (aspirin/antimalarials)

Certain foods (fava beans)

ROS generated by leukocytes in the course of infections

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17
Q

Mechanism basics of hemolysis associated with G6PD deficiency?

A

Oxidation of sulfhydryl groups on globins –>

globins denature and form Heinz bodies –>

Membrane damage

(Heinz Bod = membrane bound precipitates)

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18
Q
A
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19
Q

Symptoms of G6PD deficiency?

A
  • Anemia
  • Hemoglobinemia
  • Hemoglobinuria

(recovery associated with reticulocytosis)

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20
Q

What is sickle cell disease? What is it characterized by?

A

Hereditary hemoglobinopathy

Characterized by pdtn of defective Hb - HbS

(Normal = HbA (alpha2beta2) with a small amount of HbA2 (alpha2delta2) and HbF (alpha2gamma2)

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21
Q

What specific malaria does sickle cell protect against?

Pathogenesis?

A

Plasmodium Falciparum

Deoxygenation results in aggregation of HbS into needle-like fibers that cause RBC distortion

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22
Q

Most important factor that affects the extent of sickling?

A

Amount of HbS and its interactions with other Hb chains*

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23
Q

What is HbC? HbSC?

A

Another mutated Hb.

Individuals with HbSC have a mild form of sickle cell because HbC forms less damaging polymers when it complexes with HbS

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24
Q

Where does most sickling occur?

Pathologic manifestation?

A

Most occurs where there is stasis and in the BM

Path:

Disease is dominated by chronic hemolysis/ischmic damage from vessel occlusion.

BM: compensatory hyperplasia.

Splenic infarcts destroy the spleen eventually

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25
Q

Complications of sickle cell?

A
  • Vaso-occlusive (pain) crisis:
    • Due to infarction/hypoxic injury
  • Sequestration crisis:
    • Common in kids w/ intact spleen
    • Rapid splenomegaly from massive sequestration
  • Aplastic crisis
    • EPO completely stops due to Parvovirus B19
  • Chronic hypoxia
    • As per ush - impaired growth/development
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26
Q

Diagnosis of sickle cell?

A

Blood smear

RBC indices:

  • decreased Hb
  • decreased HcT
  • Normal or reduced MCV
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27
Q

Thalassemia syndromes:

How are they acquired? What does it result in?

What type of anemia?

A

Thalassemia syndromes:

Inherited disorders resulting in decreased production of alpha/beta-globin chain of HbA

HYPOCHROMIC MICROCYTIC ANEMIA (think youll remember this now?! jeebus. im only going to tell you once. So learn it from this single flashcard)

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28
Q

What occurs with the excess free chains in thalassemia syndromes?

A

They aggregate into insoluble inclusions that cause premature destruction of both erythroblasts and mature RBCs

29
Q

What pathologically occurs in thalassemias?

A
  • Decreased O2 transport capacity
  • Free alpha chains precipitate and form insoluble inclusions
    • This damages membranes and results in ineffective EPO
  • Compensatory erythroid hyperplasia
  • Extramedullary hematopoesis
    • In the liver, spleen, and nodes
30
Q

What can occur in severe forms of thalassemia?

A
  • Hemosiderosis
  • Hemochromatosis
    • Extreme overload
    • Damages the heart, liver, and pancreas
31
Q

Beta-Thalassemia Major:

Genetics?

When does it begin to manifest?

Hb levels?

A

Homozygous (for total absence or for severe reduction)

Manifests at 6-9 months of age

Hb = 3-6g/dL (normal is 15ish)

32
Q

RBC presentation in beta-thalassemia major? (and no.. i dont mean hypochromic microcytic)

A
  • Anisocytosis = variation in size
  • Poikilocytosis = variation in shape
  • Target Cells = Hb collects in the center
  • RBC fragmentation
33
Q

Serum changes in B-thalassemia major?

Treatment of B-thalassemia major?

A
  • Elevated reticulocyte count
  • Elevated HbF

Treatment

  • Transfusions + Iron chelation
    • Allows life into the 3rd decade
  • BM or stem cell transplant
    • Only cure
34
Q

Signs/symptoms of B-thalassemia major?

A

S/S

  • Hepatosplenomegaly
    • Due to extramedullary hematopoiesis and sequestering
  • Serious hemochromatosis may occur from overload of Fe
35
Q

What is B-thalassemia minor?

A

More common than major

Most persons are heterozygous carriers and asymptomatic

Anemia (if present) is very mild

36
Q

How many genes are there normally for alpha-globin?

A

4

37
Q

What are the four clinical syndromes of alpha thalassemia?

A
  • Silent carrier state
  • Alpha-thalassemia trait
  • Hemoglobin H disease
  • Alpha-thalassemia major
38
Q

In alpha thalassemia, what occurs in the silent carrier state?

A

Only 1 gene (of 4) is lost –> asymptomatic

39
Q

What occurs in alpha thalassemia trait?

Symptoms?

A

2 genes are deleted

Symptoms are similar to B-thalassemia minor (microcytosis w/ minimal or no signs of anemia)

40
Q

What occurs in Hemoglobin H disease (in alpha thalassemia)?

A

3 genes are deleted –> very reduced alpha chains and the occurance of HbH (B-tetramers) that have a high affinity for O2 and are not useful for exchange

41
Q

Hemoglobin H disease:

High amounts of HbH and low levels of alpha chains leads to?

Result of this condition?

A
  • High HbH/low alpha-chain
    • Tissue hypoxia
    • Inclusions in older RBCs due to oxidation
  • Results in a moderately severe anemia resembling B-thalassemia intermedia
    • MAY require periodic blood transfusions
42
Q

What occurs in alpha-thalassemia major?

Signs are similar to what?

A

All 4 genes are deleted

Gamma tetramers form but deliver no oxygen to tissues

Without intrauterine transfusions, fetal death is ineviable and the pallor/hepatosplenomegaly/edema is similar to erythroblastosis fetalis

43
Q

What is the defect in paroxysmal nocturnal hemoglobinuria?

A
  • Defect in CD59
    • Normally this blocks binding of C9 - prevents MAC-mediated lysis
  • Defect in CD55/DAF
    • Normally this accelerates the decay of C3 and C5

Thus - defective cells are very sensitive to compliment mediated lysis

44
Q

Where does the mutation for paroxysmal nocturnal hemoglobinuria occur?

How does this present?

A

Mutation occurs in pluripotent stem cells

Presentation

  • chronic intermittent intravascular hemolysis
  • Iron deficiency
  • Hemosiderinuria
  • Pancytopenia
  • Some platelets are also defective and prone to thrombosis
45
Q

In immunohemolytic anemia (HA) coombs test?

General pathogenesis?

A

RBCs are coombs test positive

Path: increased destruction of Ab-coated RBC from complement/increased phagocytosis

46
Q

Different HA syndromes?

A
  • Warm = most common; IgG
  • Idiopathic = smears w/ spherocytes and reticulocytes
    • Moderate splenomegaly and BM hyperplasia
  • Secondary HA = occurs in cancer and some AI disease
  • Drug induced HA
  • Cold Agglutinin HA = IgM
    • Common in mycoplasma/EBV/CMV/HIV/FLU
  • Cold Hemolysin HA = acute, intermittent intravascular hemolysis after exposure to cold
    • anti-RBC IgG and complement following infections
47
Q

The most important hemolytic anemias are those associated with what?

A

Associated with cardiac valve prosthesis and narrowing/obstruction of the microvasculature

48
Q

Hemolysis associated with valve prostheses and narrowing is caused by?

What is the result?

A

Shear stress produced by turbulent blood flow, abnormal pressure gradients, and/or stress of forcing RBCs through narrow vessels

(is this what its like to force a baby out??)

The result is microangiopathic hemolytic anemia commonly associated with DIC

49
Q

What are the 2 diseases associated with megaloblastic anemia?

A

Pernicious Anemia

Folate Deficiency Anemia

50
Q

General characteristics of megaloblastic anemia?

A
  • Pancytopenia w/ abnormally large cells (defective maturation)
  • RBC anisocytosis, macrocytic, oval, and hyper or normochromic
  • Increased MCV
  • Some RBCs are nucleated w/ basophilic stippling
  • Hypercellular BM
    • Megaloblasts w/ basophilic cytoplasm and fine nuclear chromatin
51
Q

Causes of B12 deficiency?

Normal B12 uptake/Metabolism?

(long notecard - refresher)

A
  • Causes of deficiency
    • Decreased intake, impaired absorption, increased requirement (preggers), parasites
  • Normal process:
    • Needed for methionine and DNA synthesis
    • B12 freed from BProteins by pepsin –> binds cobalophin –> released by proteases in the duodenum –> binds IF —> Taken up in the ileum –> binds transcobalamin and is secreted into the plasma –> delivered to liver
52
Q

Pathogenesis of pernicious anemia?

A

Autoimmune destruction of gastric mucosa –> atrophic gastritis and a lack of B12 absorption

Gastritis from inflammatory infiltrate (T cells/marophages/plasma cells)

Anti-IF Abs: one blocks binding of B12 to IF and another blocks binding of IF-B12 to ileal cells

53
Q

Clinical manifestation of pernicious anemia?

A
  • Megaloplastic anemia
    • _​_leukopenia, thrombocytopenia, and mild jaundice
  • Gastritis w/ mucosal atrophy and intestinal metaplasia
    • Increased incidence of gastric cancer
  • CNS defect in myelin synthesis in dorsal/lateral spine
    • Spastic paraparesis/sensory ataxia/Parasthesia
  • Increased risk of osteoporosis
  • Increased homocysteine
    • Atherosclerosis and thrombosis
54
Q

Diagnosis of pernicious anemia?

A
  • Macrocytosis and hypersegmented neutrophils
  • B12/folate serum levels are below normal
  • Elevated serum homocysteine
  • Abs to IF
  • Schilling test
    • measures impaired absorption of radioactive B12 corrected by administration of IF
55
Q

Anemia of folate deficiency:

What is THF important for?

What does deficiency result in?

Major causes of folate deficiency?

A

Derivatives of THF are important for purine synthesis and the conversion of homocysteine to methionine

Deficiency results in megaloblastic anemia like B12 def. but w/o CNS manifestations

Causes:

  • Grossly inadequate diet
  • Increased requirement (pregnancy/infancy)
  • Impaired metabolism
56
Q

Most common nutritional disorder worldwide?

A

Iron Deficiency anemia

57
Q

What does iron deficiency involve? What does it result in?

Where is iron found within the body?

A

Deficiency involves depletion of all iron stores w/o adequate uptake of iron resulting in microcytic hypochromic anemia

Iron:

  • 80% of functional = Hb (rest of functional in myoglobin/enz)
  • Some is stored as ferritin and hemosiderin
    • Hemosiderin in iron overloaded cells
  • Small amounts in circulation
58
Q

Causes of iron deficiency?

Clinical manifestations?

A

Deficiency due to diet or increased requirement

Most common cause of iron deficiency in developed countries if chronic blood loss.

Clinical:

  • Pallor
  • Glossitis (inflammed tongue - hawt)
  • Angular stomatitis (erosions at corners of mouth)
  • Atrophy of gastric mucosa
59
Q

Lab findings of iron deficiency?

A
  • REDUCED
    • Hb, HcT, MCV
    • Serum iron
  • INCREASED
    • Total iron binding capacity
60
Q

What is anemia of chronic disease associated with?

Common findings?

A

Associated with: chronic microbial infections, AI disorder, cancer

Common findings:

  • Low serum iron, increased serum ferritin, and reduced total iron binding capacity
    • Imply inhibition of the transfer from storage to precursor
  • Proinflammatory cytokines
    • Inhibits EPO production by the kidneys and the release of stored iron
61
Q

What does aplastic anemia result from? Associate with?

Causes of aplastic anemia?

A

Results from marrow failure and is associated with pancytopenia

Causes

  • idiopathic
  • Chemicals - dose or not-dose related
  • Physical agents - irradiation
  • Viruses - Parvovirus B19/CMV/EBV/VZV
  • Inherited - Fanconi anemia
62
Q

Pathogenesis of aplastic anemia?

A

Stem cells are altered to express foreign Ags and then be attacked by the immune system

63
Q

Clinical manifestations of aplastic anemia?

A
  • Hypocellular BM and is composed mostly of fat
  • Granulocytopenia
    • increased infections
  • Thrombocytopenia
    • bleeding disorders

RBCs present are normochromic and normocytic

64
Q

What is pure red cell aplasia?

Types?

A

Selective inhibition of erythropoiesis w/ normal granulopoiesis/thrombopoiesis

Primary: loss of progenitor cells

Secondary: associated w/ drugs or malignancy

65
Q

What is myelophthisic anemia? Result?

A

BM failure caused by replacement of the marrow (often by a malignant neoplasm)

Causes a reactive fibrosis and distortion of the marrow w/ a release of immature cells causing leukoerythroblastosis

66
Q

How does liver disease affect RBCs?

A

Affects progenitor cells

Often assiciated with lipoprotein abnormalities which affect the RBC membrane deformability –> shortened RBC life span

67
Q

How does chronic renal failure affect erythropoiesis?

A

Reduced production of EPO

68
Q

What is polycythemia?

2 classifications?

A

Abnormally high RBC count, hematocrit, and/or Hb concentration

  • Relative/apparent polycythemia
    • Associated w/ decreased plasma volume common with dehydration (from vomitting/diarrhea/burns etc)
  • Absolute/true polycythemia
    • Primary - neoplasm polycythemia vera
    • Secondary - increased EPO further classified:
      • Hypoxia driven: seen in COPD (appropriate absolute polycythemia)
      • Hypoxia independent: seen in EPO sec. tumor
69
Q
A

Pathology (11 decks)

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