matology lectures

Anemia

Soha Nageb
Lecturer of Internal Medicine
Internal Medicine Department
Faculty of Medicine
MUE
 Table of Content

Introduction Classification of anemia

03 04
Clinical pictures Management

Quiz
Erythrocyte life cycle
• Erythroid precursors develop in bone marrow at rates usually determined
by the requirement for sufficient circulating Hb to oxygenate tissues
adequately.
• Erythroid precursors differentiate sequentially from stem cells to
progenitor cells to erythroblasts to normoblasts in a process requiring
growth factors and cytokines.
• This process of differentiation requires several days.
• Normally, erythroid precursors are released into circulation as reticulocytes.
• Reticulocytes are so called because of the reticular meshwork of rRNA they
harbor.
• They remain in the circulation for approximately 1 day before they mature
into erythrocytes, after the digestion of RNA by reticuloendothelial cells.
• The mature erythrocyte remains in circulation for about 120 days before bein
engulfed and destroyed by phagocytic cells of the reticuloendothelial system
(spleen).
 Function of RBCs
• The function of the RBC is to deliver oxygen from the lungs to the
tissues and carbon dioxide from the tissues to the lungs.
• This is accomplished by using hemoglobin (Hb), a tetramer protein
composed of heme and globin
• Erythrocytes are highly deformable biconcave corpuscles
• Because erythrocytes have no nucleus, they lack a Krebs cycle and rely
on glycolysis via the Embden-Meyerhof and pentose pathways for
energy.
Definition of anemia: Anemia is low hemoglobin concentration either due to low red cell
mass or increased plasma volume(as in pregnancy).
Clinical picture of anemia
 The physiologic response to anemia varies according to acuity and the type of insult.

Gradual onset acute blood loss

allow for compensatory rapid↓ in intravascular volume,
mechanisms hypoxia and hypovolemia,
to take place with little hypotension develop rapidly .
symptoms.
 A- mild anemia
1- easy fatigability, weakness, and tiredness.
2- loss of appetite
General symptoms 3- headache, palpitation

Symptoms
B- severe anemia
1- Syncope, angina
2- Shortness of breath

Specific symptoms:
according to the
etiology of
anemia
 Specific symptoms:
• Carefully obtain a history and perform a physical examination in every patient with anemia,
because the findings usually provide important clues to the underlying disorder.
1-History of present illness:
• analysis of complaint
history of previous prior prescription of
blood studies hematinics

• GIT inquiry: upper GIT complaints that may suggest gastritis, peptic ulcers, hiatal
hernias, lower GIT tarry stools, bleeding per rectum, changes in bowel habits
(neoplasms) of the colon.
• Urinary inquiry: Abnormal urine color can occur in renal and hepatic disease and in
hemolytic anemia.
• General: Changes in body weight and appetite can suggest anemia of chronic disease (infectious, metabolic,
 • Neurological symptoms: as mentioned in folate and B12 deficiency

2- past history: carefully document pregnancies, abortions, and menstrual loss.

3- Family history not only for anemia but also for jaundice, cholelithiasis, splenectomy,
bleeding disorders, and abnormal hemoglobins.

4- Social history: A thorough dietary history is important in a patient who is anemic.

Signs
1- GENERAL EXAMINATION:
• body weight, and height for malnourished or chronic
disease.
• The skin and mucous membranes (pallor, icterus,
spider nevi, petechiae, purpura, ulcerations, palmar
erythema, coarseness of hair, puffiness of the face,
thinning of the lateral aspects of the eyebrows,
• Lymphatic system: examine for palpable enlargement of lymph nodes for evidence of
infection or neoplasia.
• Lower limb: Bilateral edema is useful in disclosing underlying cardiac, renal, or
hepatic disease,
2- Abdominal examination:
• search for hepatomegaly and splenomegaly.
• the size, the tenderness, the firmness, and the presence or the absence of nodules.
3- A rectal and pelvic examination cannot be neglected, because tumor or infection
of these organs can be the cause of anemia.
4- Cardiac examination: cardiomegaly may provide evidence of the duration and the
severity of the anemia, and murmurs may be the first evidence of a bacterial
endocarditis that could explain the etiology of the anemia.
5- Chest examination: exclude chronic diseases
4- Neurologic examination : position sense and vibratory sense, examination of the
 Classification of anemia

1- according to the pathophysiology:

Decrease Increase Blood loss

production destruction • Acute Bleeding
• BM failure • Hemolytic anemia • Chronic bleeding
• Nutritional deficiency • hypersplenism
 Classification of anemia

1- according to the size of red cells:

Microcytic Normocytic Macrocytic

• Iron deficiency anemia • Anemia of chronic disease • Folate and vitamin B12
• Thalasemia • Other hemolytic anemias deficiency (megaloblastic)
• Anemia of chronic • Aplastic anemia • Alcoholic liver disease
disease • Hemolytic anemia??
• Sideroblastic, lead poisoining

Hypothyroidism may present with micro, normo, or macrocytic anemia

.The RI is the reticulocyte count corrected for the degree of anemia in an individual
calculated as follow: normally 1-2%
Microcytic anemia
 Iron deficiency anemia (IDA)-1
CAUSES: most common

INCREASE DEMAND
With Poor diet.
INCREASE LOSS

 Malabsorption (celiac diseases is a

refractory cause of anemia). - Chronic blood loss.
 Parasitic infesation (more in childern) - GIT (peptic ulcer)
 Poverity - Menstrual blood
Signs of IDA

1- koilonychias: (spoon-shaped nails)

2- A glossy tongue: with atrophy of the lingual papillae
Angular stomatitis (fissures at the corners of the -3
mouth
Plummer- vinsons syndrome: dysphagia -4
Pica: eating dirts , clay -5
 Investigation of IDA
For diagnosis For the cause
1- Complete blood count (CBC): Microcytic hypochromic
Low mean corpuscular volume (MCV) Upper endoscopy\ lower colonoscopy -1
Low mean corpuscular hemoglobin concentration (MCHC)
Elevated platelet count (>450,000/µL) in many cases ) 2- Stool analysis parastic infestation
Normal or elevated white blood cell count

2- Peripheral blood smear: Anisocytosis and

poikilocytosis with low reticulocytic index

3- Iron profile:

• Serum iron ↓
• total iron-binding capacity (TIBC) ↑
• serum ferritin ↓
• Serum transferrtin saturation ↓
 Treatment • 3-Pharmacological:
1-Treatment of the cause
• Oral iron
• Ferrous sulphate 200 mg
2- Diet:
• Elevated retics is a sign of good
• Animal proteins versus plant response
• Continue if Hb return normal for at
proteins least 3 months to replenish stores
• Bread, contain iron chelators that markedly • IV Iron
diminish the absorption of the iron supplement • Never needed except:
(phosphates, phytates, carbonates, oxalates, • - Renal failure
tannates). • - Malabsortion
• Educate older individuals on a “tea and toast” diet • - Oral iron intolerance

about the importance of improving their diet

2-Anemia of chronic disease
It is the most commen anemia in hospital patients
Second most common types of anaemia.
Pathogensis:
Hepcidin, an endogenous antimicrobial peptide secreted by the liver regulates the intestinal absorption of dietary
iron, the release of iron from macrophages and the transfer of iron stored in the hepatocytes. Increase in hepcidin
level in the course of inflammatory disease may be a significant mediator of the accompanying anemia

Cytokines, such as interleukins (IL-1 and IL-6) and tumor necrosis factor (TNF-alpha). cause the destruction of
RBC precursors and decrease the number of erythropoietin receptors on progenitor cells.
 Decreased availability of iron

 Relatively decreased levels of erythropoietin

 Mild decrease in the lifespan of RBCs to 70-80 days

causes
Chronic infection: tuberculosis

 Chronic inflammation: rheumatoid arthritis

Chronic organ failure: renal failure

Malignancy
 Investigation of anemia
of chronic disease
For diagnosis For the cause
1- Complete blood count (CBC): normocytic normochromic
Blood sugar level -1
2- Peripheral blood smear: non specific, low reticulocytic
TSH -2
index Renal and Liver finction -3
3- Iron profile: Immunological profile -4
• Serum iron ↓
• total iron-binding capacity (TIBC) ↓
• serum ferritin ↑
Treatment
1) Treatment of underlying causes
2) Erythropoietin
3) IV iron cause raise iron in functional iron deficiency
anemia
4) Inhibitors of hepcidin and inflammatory modultors
Macrocytic anemia
Megaloblastic: a megaloblast is a cell in which •
nuclear maturation is delayed compared with the
cytoplasm. This occurs with B12 and folate
deficiency

Non-megaloblastic: Alcohol excess, •

reticulocytosis (eg in haemolysis), liver disease,
hypothyroidism
 Investigation of
For diagnosis macrocytic anemia
For the cause
1- Complete blood count (CBC): macrocytic anemia
Peripheral blood smear: Hypersegmented neutrophils -2 vitamin B12 -1
red cell folate -2
. in B12 and folate deficieny, Target cells if liver disease
Liver finction -3
Low reticulocytes TSH level -4
bone marrow: megaloblast in b12 or folate -3
deficiency
Specific tests for Pernicious Anemia:
1- Parietal cell antibodies: found in 90% with PA,
2- IF antibodies: specific for PA, but lower
sensitivity.
Investigations

Megaloblastic Non megaloblastic

anemia anemia
• ‫كل حاجه كبيره‬ • Target cells (liver
• Hypersegmented disease)
neutrophils
• Giant platelets
• ‫ وطبعا‬macrocytic
RBCs
 Folate deficiency
Folate Found in green vegetables, nuts, yeast, and liver; it is synthesized by-
gut bacteria. Body stores can last for 4 months. Maternal folate deficiency
.causes fetal neural tube defects
It is absorbed by duodenum/proximal jejunum
:Causes of deficiency
.Poor diet, e.g., poverty, alcoholics, elderly •
Increased demand, e.g., pregnancy or cell turnover (seen in hemolysis, •
malignancy, inflammatory disease, and renal dialysis)
.Malabsorption, eg coeliac disease, tropical sprue •
.Alcohol •
Drugs: anti-epileptics (phenytoin, valproate), methotrexate, trimethoprim •
 Treatment
.Assess for an underlying cause, e.g. poor diet, malabsorption -1
Treat with folic acid 5mg/day PO for 4 months, never -2
without B12 unless the patient is known to have a normal B12
level, as in low B12 states it may precipitate, or worsen,
.subacute combined degeneration of the cord
In pregnancy, prophylactic doses of folate (400mcg/day) are-3
given from conception until at least 12wks; this helps prevent
.spina bifida, as well as anemia
 Vitamin B12 deficency
• Causes of deficiency
Dietary (eg vegans: B12 is found in meat, fish, and -1
.dairy products, but not in plants)
Malabsorption: during digestion, intrinsic factor -2
(IF) in the stomach binds B12, enabling it to be
absorbed in the terminal ileum, (post gastrectomy-
terminal ileum disease, ileal resection, Crohn’s disease,
.bacterial overgrowth, tropical sprue, tapeworms
Autoimmune: atrophic gastritis ---lack of IF -3
.(pernicious anaemia)
Pernicious anaemia (PA)
• This is an autoimmune condition in which atrophic gastritis leads to a lack of IF
secretion from the parietal cells of the stomach. Dietary B12 therefore remains
unbound and consequently cannot be absorbed by the terminal ileum.
• Associations: Other autoimmune diseases thyroid disease (~25%), vitiligo,
addison’s disease, hypoparathyroidism
Carcinoma of stomach is ~3-fold more common in
pernicious anaemia, so upper GI endoscopy is needed
 Specific clinical picture of vitamin B12 deficiency
 General: Symptoms of anaemia, ‘
 Lemon tinge’ to skin due to combination of pallor (anaemia) and mild jaundice (due to haemolysis) due to
ineffective erythropoiesis
 Glossitis (beefy-red sore tongue, angular cheilosis .
 Neuropsychiatric: Irritability, depression, psychosis, dementia.
 Neurological: Paraesthesiae, peripheral neuropathy

subacute combined degeneration of the cord.

• Degeneration of the dorsal columns and the lateral columns of

the spinal cord due to demyelination, leads to paresthesia, weakness, ataxia, and
gait disturbance. In severe untreated cases, it can lead to spasticity and paraplegia.
 :Treatment
.Treat the cause if possible -1
If due to malabsorption, give hydroxocobalamin (B12) 1mg IM alternate days -2
.for 2wks then 1mg IM every 3 months for life
If the cause is dietary, then oral B12 can be given after the initial IM course (50– -3
.150mcg/daily, between meals)
Improvement is indicated by a transient marked reticulocytosis (↑MCV), after -4
4–5 days
 Bone marrow
failure
Infiltration Hematological
by malignancy
malignancy (MPD)
Aplastic
anemia
 Aplastic anemia
Definition: Aplastic anemia is a syndrome of bone marrow failure
characterized by peripheral pancytopenia and marrow hypoplasia
Signs and symptoms of aplastic anemia:
1. Pallor
2. Headache
3. Palpitations, dyspnea Anemia
4. Fatigue
5. Foot swelling
6. Gingival bleeding, petechial rashes thrombocytopenia
7. Overt and/or recurrent infections
leucopenia
8. Oropharyngeal ulcerations
Causes:

Bone marrow in aplastic anemia

Management
• supportive care only (Hematopoietic growth factors )
1. Red cells: blood transfusion, erythropoietin injection
2. Leukocytes: granulocyte colony-stimulating factor (G-CSF)
3. Platelets: either transfusion or growth factor (eltrombopag, filgrastim)

• immunosuppressive therapy
• Hematopoietic cell transplantation.
1- Which one of the following statements regarding red blood cells is false?
A) They are derived from megakaryocytes
B) Production is stimulated by erythropoietin from the kidneys
C) Increased production is associated with increased numbers of circulating
reticulocytes
D) Mature red blood cells have a biconcave disc shape
E) Mature red blood cells do not possess a nucleus or mitochondria
2- Which one of the following conditions is most likely to produce a microcytosis on
blood film examination?
A) Autoimmune haemolytic anaemia
B) Alcohol excess
C) Thalassemia
D) Vitamin B12 deficiency
E) Hypothyroidism

3- All of the following except one are recognised causes of iron deficiency anaemia.
Which is the exception?
A) Pregnancy
B) Coeliac disease
C) Cold agglutinin disease
D) Partial gastrectomy
E) Menorrhagia