Intro to Anemia Flashcards by Meghan May

What is anemia?

Decreased circulating RBC mass–>

decreased hemoglobin concentration of blood–>

decreaed O2 carrying capacity of blood–>

decreaesd O2 delivery to tissues

How well did you know this?

Not at all

Perfectly

Compensatory mechanism in anemia

Increased red cell production
Increased 2,3-DPG
Shunting of blood from non-vital to vital areas
Increased cardiac output
Increased pulmonary function

How well did you know this?

Not at all

Perfectly

What causes a right shift or for O2 to offload faster?

Decreased pH, increaed H+

increased BPG

increased temp

How well did you know this?

Not at all

Perfectly

Weakness, malaise, easy fatigability are dt:

Marrow expansion with potential bony abnormalities dt:

Pallor:

Tachycardia; cardiac ischemia:

Dysnpea on exertion:

Tissue hypoxia

Increased RBC production

Shunting of blood

Increased CO

increaed pulmon fnx

How well did you know this?

Not at all

Perfectly

• Anemia is not a disease, it is a symptom ofother diseases thus:

• All anemias need to be explained

How well did you know this?

Not at all

Perfectly

Three functional classes of anemia

Functional Classification of Anemia
• Blood Loss
• Decreased Production
• Accelerated Destruction

How well did you know this?

Not at all

Perfectly

Iron deficiency–early
Thalassemia trait
(Anemia of chronic disease)*
Some hemoglobinopathies

examples of

Microcytic , normochormic anemia

How well did you know this?

Not at all

Perfectly

Iron deficiency
Thalassemia trait
Sideroblastic anemia
(Anemia of chronic disease)*

examples of:

Microcytic, hypochromic anemia

How well did you know this?

Not at all

Perfectly

How well did you know this?

Not at all

Perfectly

– B12 and folate deficiency
– Liver disease
– Myelodysplastic syndromes
– Blood loss**
– Hemolysis**
– Some drugs

all cause:

MACROcytic anemia

How well did you know this?

Not at all

Perfectly

– Anemia of chronic disease
– Anemia of renal failure
– Marrow infiltration
– Aplastic anemia
– Blood loss**
– Hemolysis**

examples of:

Normochromic/Normocytic

How well did you know this?

Not at all

Perfectly

Key considerations when investigating anemia:

Clinical history
Physical exam
Complete blood count (CBC)
Reticulocyte count
Examination of peripheral blood smear
Specific diagnostic tests

How well did you know this?

Not at all

Perfectly

– Most important parameter for assessment of O2
-carrying capacity of blood

• Hemoglobin concentration (Hb; g/dL or g/L)
– Hemoglobin in lysed sample reacted with proprietaryreagents
– Resulting complexes measured spectraphotometrically

How well did you know this?

Not at all

Perfectly

What does Hematocrit (Hct; %) measure?

– Packed cell volume (percentage of blood volume
comprised by RBCs)
• Centrifugation (old method)
• Currently calculated as MCV x RBC

How well did you know this?

Not at all

Perfectly

Hematocrit is usually ____ hemoglobin–does not add
independent information in vast majority of cases

3 times

How well did you know this?

Not at all

Perfectly

– Direct measure of # of RBCs per unit volume
– Generally correlates well with Hb and hematocrit,
adds little independent information

Red blood cell count (RBC; # x 109/L)

How well did you know this?

Not at all

Perfectly

– Measured directly based on either electrical
impedence or light scatter
– Very useful in the differential diagnosis of anemia
(e.g., microcytic, normocytic, and macrocytic anemias)

• Mean cellular (corpuscular) volume (MCV; fL)

How well did you know this?

Not at all

Perfectly

Pt comes in with Microcytic anemia, what is on your DDx?

Iron deficiency
Thalassemia
Anemia of chronic disease

How well did you know this?

Not at all

Perfectly

Patient comes in with Macrocytic anemia, what is on your DDx?

• Megaloblastic (impaired DNA synthesis)
– B12 and folate deficiency
– Some drugs
– Myelodysplastic syndromes
• Non-megaloblastic (other mechanisms)
– Reticulocytosis
– Liver disease
– Hypothyroidism
– Some drugs

How well did you know this?

Not at all

Perfectly

Causes of Megaloblastic anemia

type of MACROcytic anemia:

(impaired DNA synthesis)
– B12 and folate deficiency
– Some drugs
– Myelodysplastic syndromes

How well did you know this?

Not at all

Perfectly

Causes of non-megaloblastic Macrocytic anemia:

– Reticulocytosis
– Liver disease
– Hypothyroidism
– Some drugs

How well did you know this?

Not at all

Perfectly

– Measure of average amount of hemoglobin per RBC
– Calculated as Hb/RBC
– High correlation with MCV

Mean corpuscular hemoglobin (MCH; pg)

How well did you know this?

Not at all

Perfectly

– Measure of “chromicity” of RBCs
– Calculated as Hb/(MCVxRBC)

How well did you know this?

Not at all

Perfectly

Mean corpuscular hemoglobin concentration (MCHC; g/dL)

How well did you know this?

Not at all

Perfectly

MCHC is: –\_\_\_\_ in hypochromic anemias –\_\_\_\_\_\_ in a few “hyperchromic” states (e.g., hereditary spherocytosis, hemoglobin CC disease

Decreased Increased

– Measure of variability of red cell volume Useful for the separation of anisocytotic anemias (e.g., Fe deficiency) from non-anisocytotic anemias (e.g., anemia of chronic disease

Red cell distribution width (RDW)

Poikilocytosis refers to:

reb blood cell shape

Descirbe the abnormal RBC and when we see it in pts

Spherocytes Round, Smaller Diameter, More densely staining, Lack of central palllor ## Footnote **hereditary spherocytosis, autoimmune hemolytic anemia**

Describe cell and when we see it:

Target cells Examples: Liver dz, splenectomy, hemoglobinopathies

Describe cell and when we see it:

Elliptocytes (ovalocytes) Examples: Hereditary elliptocytosis, megaloblastic anemia, iron deficiency, myelofibrosis

Describe the cell and when we see it:

Teardrop cells Examples: Megaloblastic anemia, myelofibrosis, extramedullary hematopoiesis

Describe cell and when we see it

Fragments (schistocytes) Examples: TTP, DIC, HUS malignant hypertension

Describe Cell and when we see it

“Bite” cells Example: Oxidant hemolysis (e.g., G6PD deficiency)

* Red cell size variability = * Average red cell size =

(anisocytosis) | (microcytosis, macrocytosis)

Hemoglobinization can be normal or too little (below is normal)

(hypochromia, normochromia)

What's with these weird cells in the PB smear?

Polychromasia: presence of reticulocytes = larger cells that look purple, sign of increased reticulocytes

What the fudge are those things?

Howell-Jolly Bodies (nuclear fragments) Examples: Splenectomy, megaloblastic anemia

What are those little nugglets? why are they in there?

Pappenheimer bodies (iron granules) Examples: Splenectomy, iron overload

It looks like that poor cell has the chicken pox, whaaaaa?

Basophilic stippling (coarse)~ defect of hemoglobin synthesis Examples: Thalassemias, MDS, lead poisoning

What is that? Why? Why is it there, WHY?

what is it called when RBC stack like coins and why does this occur?

Rouleaux Decreased repulsive forces between RBCs Examples: Increased serum proteins (Ig, fibrinogen)

Why do RBC clump up in this image?

Agglutination Examples: IgM RBC antibodies (cold agglutinins) that are xlinking

Anemia of Blood Loss--Acute What happens initially? When do we see signs of anemia?

* Initially no anemia by CBC parameters despite decrease in blood volume * Anemia develops as tissue fluid enters vascular space to restore blood volume, producing dilution of cellular elements

In anemia of acute blood loss: Reticulocyte count increases after \_\_\_\_days and peaks after \_\_\_\_\_

2-3 7-10 days

Anemia of Blood Loss--Chronic • No anemia initially because: • *Slight reticulocytosis*

marrow is able to compensate

In anemia of chronic blood loss, what occurs eventually?

• Eventual development of iron deficiency with resultant iron deficiency anemia

Sites of RBC production – Embryo: \_\_\_\_ – Fetus (3 months gestation until birth): – Shortly after birth through adult life:

Yolk sac Liver BM

How is RBC production regulated in terms of oxygen delivery and EPO?

– Decreased oxygen delivery induces the production of **erythropoietin by kidney** – Erythropoietin causes p**roliferation and differentiation** of _committed progenitor cells_ (EPO--\>CFU-E to inducte Erythroblasts to become RBC)

Normoblastic Maturation • Normoblasts (nucleated RBC precursors) obtain iron from _______ for hemoglobin synthesis

plasma transferrin

Up to _____ produced from each pronormoblast (earliest morphologically recognizable erythroid precursor)

16 reticulocytes \*\*• Roughly equal numbers of reticulocytes and normoblasts in marrow

As we go vrom Stemcell to RBC in the normoblastic maturation, what happens to Hemoglobin and RNA?

Hemoglobin INCREASES RNA DECREAES \*cells shrink and will lose nucleus

What is pictured below?

pronormoblast (earliest morphologically recognizable erythroid precursor) very roud regular nuclei with concentric ring of cytoplasm \*\*\*basophilic normoblasts are more basophilc and look simular

Admix of RNA and proteins, just note polychromatophilcl and basophilic thing

look at picture before

Earliest anucleate erythroid form • Larger than mature RBCs • Contain residual RNA which gives cytoplasm a blue tinge on routinely stained blood smears (polychromasia)

Reticulocytes

How long to reticulocytes reside in marrow and what do they do there?

Stay in marrow for 1 to 2 days synthesizing hemoglobin before being released into circulation

Reticulocytes: • Normally circulate for approximately \_\_\_\_before losing residual ribosomes, mitochondria, and other organelles to becoming \_\_\_\_\_\_\_ • Normally \_\_% of peripheral erythrocytes

one day , mature erythrocytes 1%

How can we detect reticulocytes? • Used as measure of marrow RBC production – Cleaves anemias broadly into those with decreased red cell production and those with adequate marrow response to blood loss or increased RBC destruction

Can be detected using RNA stains to obtain a “reticulocyte count” – Expressed as % of total RBCs

Used as measure of marrow RBC production – Cleaves anemias broadly into those with decreased red cell production and those with adequate marrow response to blood loss or increased RBC destruction

Reticulocytes

The Reticulocyte Count • Problem: • Solution: Corrected reticulocyte percentage – Retic% x (patient HCT/45) • Better Solution:

Reticulocyte % varies depending on total RBC count Absolute reticulocyte count

Decreased RBC Production leads to what 3 problems

• Ineffective erythropoieis • Decreased RBC precursors (marrow failure) • Anemia of chronic disease (anemia of inflammation)

Decreased red cell production despite increased RBC precursors in marrow • Characterized by **defects in maturation**

Ineffective Erythropoiesis

Three examples of Ineffective erythropoiesis

– Iron deficiency (cytoplasmic maturation defect) – Megaloblastic anemia (nuclear maturation defect) – Myelodysplastic disorders

Features of Ineffecitve Erythropoiesis: Ineffective Erythropoiesis: General Features • Prominent\_\_\_\_\_\_ abnormalities of erythrocytes due to disordered mutation •\_\_\_\_\_\_ of erythroid precursors in marrow • Decreased\_\_\_\_\_ count despite increased erythroid mass in marrow

morphologic Dysmaturation reticulocyte

Proliferation Defect characterized by an absolute decrease in the marrow mass of erythroid precursors

Decreased RBC precursors

Cause of absolute decrease in the marrow mass of erythroid precursors seen in Decreased RBC Precursors

– Decreased erythroid progenitors available for RBC production or – Decreased proliferative capacity of numerically adequate erythroid progenitor

– Usually normochromic/normocytic – Usually little anisopoikilocytosis (compared to maturation defects/ineffective erythropoiesis) – Decreased reticulocyte counts

General features of Decreased RBC precursors:

Decreased RBC Precursors • Stem cell defects with adequate erythropoietin: 3 causes

Red cell aplasia (pure) vs. pan-aplasia (aplastic anemia) – Congenital – Acquired

Diamond-Blackfan syndrome (pure red cell aplasia) • Fanconi’s anemia (pan-aplasia) both examples of:

congenital Stem cell defects with adequte erythropoietin (see decreased RBCs)

In Decreased RBC precursors we can see marrow replacement caused by what?

– Leukemias/lymphomas – Metastatic carcinoma – Fibrosis – Storage disease

Decreased EPO could case decreased RBC precursors, when would we see that?

Anemia of renal failure

* Inflammatory block in erythropoiesis * Thought to be mediated by IL-1, TNF-alpha, and IFN gamma * Probably multiple mechanisms

Anemia of Chronic Disease

General properties of RBCs

• **Biconcave disc** – 7.5-8.7 m in diameter – Average volume of 90 fl **• Special membrane structure which provides durability, flexibility, and tensile strength** – Can swell to a _volume of 150 fl_ – Can get through a _2.8 m diameter capillary_ – Springs back to original shape after distortion

Key in RBC membrane cytoskeleton

ankyrin Beta spectrin Alpha spectrin \*\*\*RBC should be able to do red cell

Accelerated RBC Destruction (Hemolysis) • Red cells normally circulate for ~120 days • Increased destruction results in

increased marrow production – 8 times normal in ideal circumstances • Enough iron • Enough folate • Otherwise good health

• When rate of destruction exceeds bone marrow’s ability to compensate,\_\_\_\_\_ develops – we see a new steady state at \_\_\_\_\_

anemia lower hemoglobin level

Predominates in most forms of hemolytic anemia • Final common pathway: Decreased RBC deformability

Extravascular Hemolysis

What results from decreased RBC deformability seen in Extravascular hemolysis?

– Rigid, non-deformable cells have trouble traversing narrow slits between splenic cords and sinusoids – Cells are damaged further with prolonged exposure to splenic cordal environment – Damaged cells phagocytized by cordal macrophages

What is the fate of Hemoglobin in the Intravascular pathway?

Hemoglobin + Haptoglobin --\> to the liver 1/2 = 10-30 mins

What is the fate of Hemoglobin in the extravascular pathway?

taken up by splenic macrophage and combines with lysosome--\> get lipid + protein + heme breakdown

Heme --\> Biliveridin how? Biliveriden --\> Bilirubin how?

via Heme oxygenase Biliveridin Reductase

Features of Hemolysis * \_\_\_\_\_ indirect bili from heme metabolism * \_\_\_\_\_ LDH released from destroyed RBCs * \_\_\_\_\_ haptoglobin

Increased Increased Decreased

Features of hemolysis: • Splenomegaly in ____ cases • Bony abnormalities in _____ hemolytic anemias

chronic severe chronic