Join Our Telegram Channel at Medico Study (@medicostudy)

MEDICO STUDY
General overview of Anemia

Table of Contents
Anemia .......................................................................................................................................................... 1
Classification ............................................................................................................................................. 1
Morphological classification ..................................................................................................................... 1
Pathophysiologic classification ................................................................................................................. 1
1. Decreased production................................................................................................................... 2
2. Increased destruction (occurring due to hemolysis) .................................................................... 3
Pathophysiology of anemia of chronic disease/inflammation ..................................................................... 6
Join Our Telegram Channel at Medico Study (@medicostudy)
Join Our Telegram Channel at Medico Study (@medicostudy)

Anemia
Is a condition in which the number of red blood cells or the hemoglobin concentration within RBCs is
lower than normal. [WHO]

Is when the hemoglobin/hematocrit level is lower when compared to age & gender defined ranges.

*The above measurements are in g/L; to convert to g/dL, just divide by 10.

* Erythropoiesis requires: -

 Intact (proliferating) BM
 Adequate amount of Erythropoietin (EPO)
 Iron
 Effective maturation of RBCs

Classification
 There are various ways of classifying Anemia.
 Mainly there is morphological and pathophysiologic classification.

Morphological classification
Is based on RBC size, Hemoglobin content and Shape.

 Based on RBC size: Macrocytic vs. microcytic vs. normocytic

 Based on Hemoglobin Content: Hypochromic vs. normochromic
 Based on Shape: Normal or abnormal (spherocytes, sickle shaped…)

Pathophysiologic classification
Is based on the underlying cause for the decrease in the RBCs.

1. Anemia caused by decreased production of RBCs.

2. Anemia caused by increased destruction or loss of RBCs.
2.1. Due to an intra-corpuscular abnormality or
2.2. Due to an extra-corpuscular abnormality
3. Anemia caused by acute blood loss (severe)

1
Join Our Telegram Channel at Medico Study (@medicostudy)

* Intra-corpuscular abnormality: is the consequence of an abnormality in the red cell membrane, an

enzyme, or globin chain (inherited condition)

* Extra-corpuscular abnormality: is secondary to a clinical condition (acquired condition).

*Please take time to review and understand the next table about pathophysiologic classification.

1. Decreased production
As mentioned in the beginning, erythropoiesis/RBC production requires adequate amount of iron, EPO
and intact bone marrow. If any of these are affected, the production of RBCs will be affected.

1.1. Defective precursor proliferation can occur due to

 Iron deficiency anemia
 Anemia of chronic renal failure: which results in decreased EPO production
 Anemia of chronic disease (mechanism to be explained in detail within Bone marrow failure syndrome
the next pages)
 Problems with the bone marrow Is a group of disorders that may
o Bone marrow failure syndromes manifest as single cytopenia (e.g.,
o BM infiltration (leukemia, lymphoma, metastasis and fibrosis) erythroid, myeloid, or
 Aplastic anemia megakaryocytic) or as
pancytopenia.

Can be either inherited or

acquired.

2
Join Our Telegram Channel at Medico Study (@medicostudy)

1.2. Defective Precursor Maturation: Maturation is in both cytoplasm as well as DNA therefore both
could be affected. If the nuclear maturation is affected- DNA synthesis will be affected. If
Cytoplasmic maturation is affected, the hemoglobin production will be affected.

What affects Nuclear Maturation? In Myelodysplastic syndromes,

bone marrow cells display aberrant
- Megaloblastic anemia morphology and maturation
- Myelodysplastic syndrome (dysmyelopoiesis), resulting in
- Chemotherapy ineffective blood cell production.
What affects Cytoplasmic maturation (defective Hgb production)? i.e. Marrow activity is normal but
*Hemoglobin (Hgb) is made of heme and globin. Heme contains iron. produces defective cells.

If any of these are affected, cytoplasmic maturation will be affected.

e.g. -Iron Deficiency Anemia (IDA)

-Heme synthesis defect (e.g. sideroblastic Anemia.)

-Globin synthesis defect (e.g. thalassemia)

2. Increased destruction (occurring due to hemolysis)

Hemolytic anemia can be due to either inherited or acquired conditions.

2.1. Due to Inherited conditions/Intrinsic defect/Intracorpuscular

- Defects of red blood cell membrane (as in hereditary spherocytosis and hereditary
elliptocytosis)
- Defects in hemoglobin production (as in thalassemia, sickle-cell disease)
- Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase [G6PD] deficiency and
pyruvate kinase deficiency[PKD])
- Paroxysmal nocturnal hemoglobinuria (PNH)- is actually acquired (Take a look at the box below
for explanation)

Paroxysmal nocturnal hemoglobinuria (PNH)

- Although not an inherited disease, PNH is a genetic disorder,

known as an acquired genetic disorder.

- What it means by acquired genetic disorder is that –it is

caused by acquired mutations or changes in parts of the
DNA. Such conditions only become heritable for the next
generation if the mutation occurs in the germ line.

- Mechanism: occurs due to the absence of protective

proteins on the RBC’s membrane. As a result, the RBCs will
be destroyed by the complement system. 3
Join Our Telegram Channel at Medico Study (@medicostudy)

2.2. Due to acquired conditions/extrinsic/extra corpuscular

- Immune-mediated causes: could include transient factors as in Mycoplasma pneumoniae

infection (cold agglutinin disease) or permanent factors as in autoimmune diseases like
autoimmune hemolytic anemia- SLE, rheumatoid arthritis, Hodgkin's lymphoma, and chronic
lymphocytic leukemia
- Physical trauma to the RBCs: Low-grade hemolytic anemia occurs in 70% of prosthetic heart
valve recipients and severe hemolytic anemia occurs in 3%
- Certain infections e.g. malaria

- Any of the causes of hyper splenism (increased activity of the spleen), such as portal
hypertension
- Lead poisoning resulting from the environment causes non-immune hemolytic anemia
- Runners can suffer hemolytic anemia owing to the destruction of red blood cells in feet at foot
impact

The next classification is based on morphology: RBC size based on mean corpuscular volume (MCV)

Microcytic Anemia Normocytic Anemia Macrocytic Anemia

To easily memorize -After we diagnose anemia with
causes of microcytic, low Hgb; if one of the RBC
think of the indices i.e. MCV IS normal. Then
cytoplasmic content the functionality of the marrow
of RBC should be checked.
Hgb: - Heme/Fe & -Reticulocytes will be produced
Globin. to replenish the depleted RBCs.
Thus, increased production
*More on Anemia of
indicates compensation for loss.
chronic disease- on
the next pages. -Normal Corrected Reticulocyte
count: 0.5% - 1% or 0.5% -1.5%
As seen in the picture above, macrocytic anemia
can be classified as Megaloblastic or Non-
Megaloblastic. This is differed by Peripheral blood
smear.
In megaloblastic: we see immature large RBCs
which are called megaloblasts. Additionally we see
hyper-segmented neutrophils. Occurs due to B12,
Folate, Drug induced such as Methotrexate/those
that interfere with DNA synthesis.
4
In non-megaloblastic - Mature large RBCs are
seen. Due to Alcohol abuse, hypothyroidism,
Pregnancy
 Join Our Telegram Channel at Medico Study (@medicostudy)

Microcytic Anemia Normocytic Anemia Cont.

Cont.
Other Causes:
Causes:
Early stage of Anemia of chronic disease
Iron deficiency Anemia [includes chronic renal failure] and Iron
deficiency Anemia
Anemia of Chronic
disease

Sideroblastic anemia *Corrected Retic Count is important to

evaluate if the marrow response is adequate
Thalassemia
for the level of anemia.
Lead poisoning
= reticulocyte % × (patient Hct/normal Hct)

Hyper-segmented
neutrophils

Lymphocyte;

The rest are

RBCs

Red blood cells (erythrocytes) are biconcave disks

with a diameter of 7-8 microns, which is similar to
the size of the nucleus of a resting lymphocyte.

5
Join Our Telegram Channel at Medico Study (@medicostudy)

Pathophysiology of anemia of chronic disease/inflammation

(Hepcidin causes increased internalization of ferroportin molecules on cell membranes which prevents
release from iron stores. Inflammatory cytokines also appear to affect other important elements of iron
metabolism, including decreasing ferroportin expression, and probably directly blunting erythropoiesis
by decreasing the ability of the bone marrow to respond to erythropoietin.)

 Slightly shortened RBC survival: due to increased hemophagocytosis by macrophages, occurs in

patients with inflammatory diseases.
 Erythropoiesis is impaired: because of decreases in both erythropoietin (EPO) production and
marrow responsiveness to EPO.
 Iron metabolism is altered due to an increase in hepcidin, which inhibits iron absorption and
recycling at the duodenum/enterocytes, leading to iron sequestration.

----------------------------------------------------------------------------------------------------------------------------------------

For more materials such as this, go to our Telegram channel: - Medico Study (@medicostudy)

Next study material will focus on approach to anemia and Iron deficiency anemia.