Anemia, its classification.

Eosinophils , Neutrophils
Their morphology,
abnormality and role in
injury & Inflammation.

Presented by; Syeda Iqra Ahmad

Presented to; Sir Khalid Abdul
Majeed
• Anemia refers to significant reduction in mass of
RBC,s which retards to oxygen binding capacity
of Hb. Low hematocrit is a subrogate value for
anemia.
• Hb level < 12 g/dl for females and 13g/dl for
males denotes anemia. (WHO)
• Age and Gender Dependent.
• Abundant in children, young women and elder
people mainly due to malnutrition (90%). Up to
1.62 Billion population of world.
• Fatigue
• Dizziness
• Dyspnea
• Pallor of the conjunctivae, face, nail beds and
palmar creases
• Cold skin
• Palpitation to pulmonary edema
• Impairment of congnitive function
• Hematuria (red urine)
Its classification based on three factors
I. Pathogenesis
II. Red cell morphology
III. Clinical presentation
Inadequate production and loss of erythrocytes a
result of bleeding or hemolysis.
Bleeding may be internal or external
Internal Bleeding; erythrocytes are break down
within the body and plasma proteins has not lost
from the body.
External Bleeding; Loss of plasma proteins as
well as erythrocytes
 Hypo-regenerative: When bone marrow production
is decrease as a result of impaired function, decreased
number of precursor cells, reduced bone marrow
infiltration, or lack of nutrients.
Reason ; Alteration of bone marrow progenitor cells,
at any stages of differentiation and maturation. The
impairment of pluripotent stem cells usually produces
pancytopenia (anemia, leukopenia and
thrombocytopenia
• Bone marrow failure caused by stem cell.
Inherited: hereditary dyserythropoiesis
• Acquired: Myelodysplasia
• Bone marrow infiltration
• Solid tumors
• Inflammatory chronic diseases. Microorganisms
Drugs, hypothyroidism, uremia
• Erythropoietic factors deficiency e.g., Iron,
Cobalamin and folate.
• Hormones: erythropoietin, thyroid hormones,
androgens, steroids
 Regenerative: when bone marrow responds
appropriately to a low erythrocyte mass by
increasing production of erythrocytes
Reason;
Increased generation of erythropoietin in
response to decreased hemoglobin conc. and
generally reflects a loss of erythrocytes, due to
bleeding or hemolysis
 Acute or chronic bleeding
 Hemolytic anemia Hereditary
(hemoglobinopathy, enzymopathy, membrane-
cytoskeletal defects)
 Acquired (autoimmune, mechanical
destruction, toxic-metabolic, drugs, infectious,
PNH, hypersplenism)
Normocytic normochromic anemia in which the
circulating red blood cells (RBCs) are the same size
(normocytic) and have a normal red color
(normochromic) up 39% of anemia It is mainly due
to
• Nutritional deficiency e.g., Iron (IDA)
• Renal failure
• Anemia of chronic disorders (ACD)
• Endocrinopathy (myxedema, Addison disease,
hypothyroidism, panhypopituitarism)
• Anemia of liver disease
(Chulilla et al. 2009)
 Nutritional anemia (iron deficiency, cobalamin
y/o folate)
 Anemia of renal insufficiency
 Red cell intrinsic causes: membranopathy,
enzymopathy, hemoglobinopathy
 Red cell extrinsic causes: immune-mediated,
microangiopathic, associated with infection,
chemical agent metabolic ACD Primary bone
marrow disorder
 Macrocytic anemia refers to macrocytosis
(mean corpuscular volume (MCV) greater than
100 fL). up to 1.7% to 3.9%.
Megaloblastic in which abnormal large nucleus is
present due to impaired DNA synthesis from
folate or vitamin B12 deficiencies.
Non-Megaloblastic in which normal nucleus
with large size of RBC,s occurs from multiple
mechanisms (Moore and Adil 2017)
 Drugs (hydroxyurea, zidovudine,
methotrexate)
 Nutritional (vitamin B12 and folate
deficiency)
 Excess alcohol intake, liver disease, smoking
Hypothyroidism, Waldenström’s
macroglobulinemia Copper deficiency, bone
marrow aplasia, erythroblastopenic anemia
 Down syndrome
 Chronic obstructive pulmonary disease
 Microcytic (Hypochromic) anemia refers to
presence of small, often hypochromic, red
blood cells in a peripheral blood smear and is
usually characterized by a low MCV (less than
83 micron, 3%).
Reasons;
Iron deficiency anemia (IDA)
Thalassemia
Anemia of chronic disorders (ACD)
(Akrimi et al. 2013)
 A Type of White blood cell that is an important part
of the immune system and helps the body to fight
against infection.
Function;
 When microorganisms e.g., bacteria , viruses or
other injurious agents enter the body, these are first
immune cells to respond. They travel to the site of
infection, to destroy the microorganisms by
ingesting them and releasing enzymes to kill them.
 Boost the response of other immune cells.
 Also served as granulocyte and a type of phagocyte
1. Hematopoietic stem cells (HSC) forms and formed
multipotent plueoric potential stem cells (MPP)
2. MPPs give rise to lymphoid-primed multipotent
progenitors (LPMP).
3. LPMP differentiate into granulocyte-monocyte
progenitors (GMP).
4. GMP transformed into myeloblasts.

Maturation Myeoblast stages Promyelocyte Myelocyte

Metamyelocyte Band cell Mature neutrophil

~1011 cell per day

• Mature neutrophils 12 to 15 µm and exhibit 3-5
nuclear lobes, while females may display a
'drumstick' that protrudes from the nucleus.
• Neutrophils contain primary and secondary
granules.
• Primary granules are azurophilic (Burgundy-
colour) and contain toxic mediators such as
elastase and myeloperoxidase.
• Secondary granules are pink-staining and contain
proteins such as lactoferrin; these are not usually
visible by light microscopy.
(Rosales 2018)
Normal Neutrophil
Type Features Causes
Hypersegmented Presence of hypersegmented neutrophils, with five or Megaloblastic
Neutrphils more nuclear lobes anemia,
Myelodysplastic
syndrome
Toxic Granulated Increase in the number of large basophilic granules Infection or
Neutrophils within circulating neutrophils. inflammation.

Hypogranular Less granules than normal. Myelodysplastic

Neutrophils syndrome.

Vacuolated Presence of vacuoles within neutrophils on a blood Infection, G-CSF

Neutrophils film is highly suggestive of infection. Acute heavy
alcohol intake

Dohle Bodies Dohle bodies are blue cytoplasmic inclusions seen Stress, Burns,
Neutrophils within neutrophils. These inclusions are remnants of Trauma
the rough endoplasmic reticulum
Type Features Causes

Neutrophilia Presence of increased circulating neutrophils, pyogenic infection,

and is a common finding in the full blood post-surgical state
count of acutely unwell patients. Inflammation,
Long-term smoking,
Acute stress ,
Myeloproliferative
disorders,
Corticosteroids
Neutropaenia Reduced circulating neutrophils. viral infection, Dietary
deficiency mainly
B12 and folate
deficiency
Infection; Antimicrobial functions of neutrophils
 Phagocytosis,
 Degranulation,
 Release of nuclear material in the form of neutrophil
extracellular traps (NETs)
Inflammation ; neutrophils regulate inflammation by
increasing cytokines and immune response. Recent research
indicates that they also provoked other neighboring cells to
produce cytokines as well as modulation of immune system
by promoting macrophages long-term immunity
(Rosales 2018)
 Major effector cells in the immune system
 Activated cells that defend the body
from bacteria, viruses, parasites, and
other pathogens.
 Produced in bone marrow & then transported
everywhere in body but mainly found in digestive
and respiratory system.
 Usually stay for 8- 12 days but their half life is 4.5
to 8 hrs.
Their ranged from 0.5 to 1 % of blood cells.
 Formed in bone marrow.
 SCF, IL-3, IL-4, GM-CSF and CCL11, IL-5
and CCL11 converts HPS converts into
eosinophils by differentiation, maturation and
release of Eosinophils from the bone marrow
into the bloodstream.
 CCR3, the receptor for CCL11 are receptors
of eosinophils for cytokines, chemokines and
lipid mediators for inflammation.
• A membrane that surrounds the cell
cytoplasm.
• Approximately 8ũ in diameter.
• A liquid inside the cells that surrounds the
granules
• Around 200 microscopic granules that
release substances such as cytotoxins,
which kill unwanted cells
• A nucleus with 2 lobes (bilobed)
• Their concentration increases during
asthma in allergic reactions of in body.
( https://www.medicalnewstoday.com/articles/311601)
Eosinophils exhibit their biological activity
mainly by cytotoxic mediators such as
a. Type 1 & type 2 cytokines,
b. Chemokines ,
c. Lipid mediators
d. Acute inflammatory cytokines.
Eosinophils have ability to repair muscle damage as
regeneration.
 Muscle injury can be healed by resident
fibrocyte-adipocyte progenitors (FAPs).
 Angiogenesis by the production of pre-formed
pro-angiogenic mediators, among others the
vascular endothelial growth factor (VEGF).
 Eosinophil-derived IL-4 is also required for
liver regeneration
 Eosinophils confer protection following
myocardial infarction
(Lombardi et al. 2022)
Eosinophilia high level of eosinophils in the blood or body
tissues. This is not a disease but a sign that another health
problem is present.
Reasons;
 Parasitic, bacterial, fungal, or viral infections
 Leukemia, cancerous tumors
 Eosinophilic granuloma a benign tumor on the bone
 Allergies, upper respiratory diseases
 Asthma and eosinophilic asthma
 Immune-mediated diseases, such as systemic sclerosis and
primary biliary cirrhosis
Sensitivity to certain drugs, such as antibiotics
Eosinopenia: very low levels of eosinophils,
although there is no specific range.
 Allergy occurs when a person reacts to substances in the
environment that are harmless to most people.
Allergens; Substances caused allergy found in dust mites, pets,
pollen, insects, ticks, moulds, foods and some medications.
Mechanism;
o When the allergen (such as pollen) enters the body, it triggers
an antibody response.
o The antibodies attach themselves to mast cells.
o When the pollen comes into contact with the antibodies, the
mast cells respond by releasing histamine.
o When the release of histamine is due to an allergen, the
resulting inflammation (redness and swelling) is irritating and
uncomfortable.
 Infection occurs when a microorganis enters a
person’s body and causes harm. The effects of
infections occur due to the immune system’s attempt
to get rid of the invading organism.
Types;
I. Viral infections.
II. Bacterial infections
III. Fungal infection
IV. Protozoal infection
V. Helminthes infection
• Viruses are tiny, range from 20 to 400 nm in diameter
particles and appears as crystals outside the leaving
body due to lack of its own self sufficiency.
• These are simple packets of nucleic acid, either DNA or
RNA, surrounded by a protein shell and sometimes fatty
material
• It enters a host cell and go into action, hijacking the
cell’s metabolic machinery to produce copies of itself
that may burst out of infected cells to produce infection.
Diseases; Common cold, measles, chicken pox, genital
herpes, influenza, AIDS and SARS
• Bacteria are 10 to 100 times larger than viruses and are
self-sufficient
• Most bacteria carry a single circular molecule of DNA,
which encodes the essential genes for reproduction and
other cellular functions
• They reproduce by dividing into two cells, a process
called binary fission. Their offspring are identical,
essentially clones with the exact same genetic material
and their high population cause infection.
Infectious Disease; Strep throat, tuberculosis, staph skin
infections, urinary tract and bloodstream infections.
Fungal Infection;
Spore-forming organisms that range from bread mold to
ringworm to deadly histoplasmosis.
Protozoal infection;
Agents behind malaria mainly by Plasmodium
falciparum and dysentery caused by Entamoeba
histolytica.
Helminthes infection;
Parasitic worms like those that cause trichinosis,
hookworm, and schistosomiasis.
(Drexler 2014)
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Abnormal Morphologic Shapes of The Erythrocytes upon the Different Types of Anemia.
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3. Drexler M. 2014. What you need to know about infectious disease.
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5. Lombardi C, Berti A, Cottini M. 2022. The emerging roles of eosinophils: implications for
the targeted treatment of eosinophilic-associated inflammatory conditions. Current
research in immunology. 3: 42-53.
6. Moore CA, Adil A. 2017. Macrocytic Anemia.
7. Rosales C. 2018. Neutrophil: a cell with many roles in inflammation or several cell types?
Frontiers in physiology. 9: 324475.
8. Tvedten H. 2022. Classification and laboratory evaluation of anemia. Schalm's veterinary
hematology. 198-208.
9. Yilmaz G, Shaikh H. 2023. Normochromic Normocytic Anemia. StatPearls Publishing,
Treasure Island (FL).
10. https://www.allergy.org.au/patients/about-allergy/what-is-allergy
11. https://www.medicalnewstoday.com/articles/311601(Lombardi et al. 2022)
12. https://medschool.co/tests/blood-film/neutrophil-morphology