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Pathology > Chapter 14 - RBCs and Bleeding Disorders > Flashcards

Chapter 14 - RBCs and Bleeding Disorders Flashcards

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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
Complications of sickle cell?
* _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
26
Diagnosis of sickle cell?
Blood smear RBC indices: * decreased Hb * decreased HcT * Normal or reduced MCV
27
Thalassemia syndromes: How are they acquired? What does it result in? What type of anemia?
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)
28
What occurs with the excess free chains in thalassemia syndromes?
They aggregate into insoluble inclusions that cause premature destruction of both erythroblasts and mature RBCs
29
What pathologically occurs in thalassemias?
* 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
What can occur in severe forms of thalassemia?
* Hemosiderosis * Hemochromatosis * Extreme overload * Damages the heart, liver, and pancreas
31
Beta-Thalassemia Major: Genetics? When does it begin to manifest? Hb levels?
Homozygous (for total absence or for severe reduction) Manifests at 6-9 months of age Hb = 3-6g/dL (normal is 15ish)
32
RBC presentation in beta-thalassemia major? (and no.. i dont mean hypochromic microcytic)
* Anisocytosis = variation in size * Poikilocytosis = variation in shape * Target Cells = Hb collects in the center * RBC fragmentation
33
Serum changes in B-thalassemia major? Treatment of B-thalassemia major?
* Elevated reticulocyte count * Elevated HbF Treatment * Transfusions + Iron chelation * Allows life into the 3rd decade * BM or stem cell transplant * Only cure
34
Signs/symptoms of B-thalassemia major?
S/S * Hepatosplenomegaly * Due to extramedullary hematopoiesis and sequestering * Serious hemochromatosis may occur from overload of Fe
35
What is B-thalassemia minor?
More common than major Most persons are heterozygous carriers and asymptomatic Anemia (if present) is very mild
36
How many genes are there normally for alpha-globin?
4
37
What are the four clinical syndromes of alpha thalassemia?
* Silent carrier state * Alpha-thalassemia trait * Hemoglobin H disease * Alpha-thalassemia major
38
In alpha thalassemia, what occurs in the silent carrier state?
Only 1 gene (of 4) is lost --\> asymptomatic
39
What occurs in alpha thalassemia trait? Symptoms?
2 genes are deleted Symptoms are similar to B-thalassemia minor (microcytosis w/ minimal or no signs of anemia)
40
What occurs in Hemoglobin H disease (in alpha thalassemia)?
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
Hemoglobin H disease: High amounts of HbH and low levels of alpha chains leads to? Result of this condition?
* 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
What occurs in alpha-thalassemia major? Signs are similar to what?
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
What is the defect in paroxysmal nocturnal hemoglobinuria?
* 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
Where does the mutation for paroxysmal nocturnal hemoglobinuria occur? How does this present?
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
In immunohemolytic anemia (HA) coombs test? General pathogenesis?
RBCs are coombs test positive Path: increased destruction of Ab-coated RBC from complement/increased phagocytosis
46
Different HA syndromes?
* _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
The most important hemolytic anemias are those associated with what?
Associated with cardiac valve prosthesis and narrowing/obstruction of the microvasculature
48
Hemolysis associated with valve prostheses and narrowing is caused by? What is the result?
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
What are the 2 diseases associated with megaloblastic anemia?
Pernicious Anemia Folate Deficiency Anemia
50
General characteristics of megaloblastic anemia?
* 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
Causes of B12 deficiency? Normal B12 uptake/Metabolism? (long notecard - refresher)
* 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
Pathogenesis of pernicious anemia?
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
Clinical manifestation of pernicious anemia?
* _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
Diagnosis of pernicious anemia?
* 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
Anemia of folate deficiency: What is THF important for? What does deficiency result in? Major causes of folate deficiency?
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
Most common nutritional disorder worldwide?
Iron Deficiency anemia
57
What does iron deficiency involve? What does it result in? Where is iron found within the body?
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
Causes of iron deficiency? Clinical manifestations?
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
Lab findings of iron deficiency?
* _REDUCED_ * Hb, HcT, MCV * Serum iron * _INCREASED_ * Total iron binding capacity
60
What is anemia of chronic disease associated with? Common findings?
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
What does aplastic anemia result from? Associate with? Causes of aplastic anemia?
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
Pathogenesis of aplastic anemia?
Stem cells are altered to express foreign Ags and then be attacked by the immune system
63
Clinical manifestations of aplastic anemia?
* Hypocellular BM and is composed mostly of fat * Granulocytopenia * increased infections * Thrombocytopenia * bleeding disorders RBCs present are normochromic and normocytic
64
What is pure red cell aplasia? Types?
Selective inhibition of erythropoiesis w/ normal granulopoiesis/thrombopoiesis _Primary_: loss of progenitor cells _Secondary_: associated w/ drugs or malignancy
65
What is _myelophthisic anemia_? Result?
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
How does liver disease affect RBCs?
Affects progenitor cells Often assiciated with lipoprotein abnormalities which affect the RBC membrane deformability --\> shortened RBC life span
67
How does chronic renal failure affect erythropoiesis?
Reduced production of EPO
68
What is polycythemia? 2 classifications?
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

Pathology (11 decks)

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