Cell morphologies and causes

Question 1

Macrocytosis

Answer 1

Definition:
* RBC size > 100 fL (Mean Corpuscular Volume, MCV)

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Common Causes (M/c/c):
* Alcoholism
* Vitamin B12 deficiency
* Folate deficiency
* Myelodysplastic syndrome**

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Uncommon Causes:
* Reiculocytosis
* Liver disease (non-alcoholic or alcoholic)
* Multiple myeloma
* Acute leukemia
* Hypothyroidism

mnemonic- RML Hospital

Question 2

Nucleated RBCs

Answer 2

Key Concept:
* Indicates bone marrow (B.M.) stress or immaturity of RBC production
* B.M. may be:
* Struggling to keep up with losses
* Lacking sufficient resources (e.g. nutritional deficiencies)
* Stimulated erythropoiesis (emergency production)

1. Problem in Production:
   
   • Malignant infiltration of B.M.
   • Anemia
   • Extramedullary hematopoiesis
   • Stimulated erythropoiesis
2. Problem in Maintenance:
   
   • Hypoxia (↑ demand)
   • Nutritional deficiencies
   • Sepsis (↑ demand)
   • Liver disease
3. Decreased Destruction:
   
   • Post-splenectomy
   • Hemolysis

mnemonic- SHAMELS

Question 3

Rouleaux formation

Answer 3

• Stacks of RBCs are formed due to bridging of macromolecules.

Mechanism:
* Bridging occurs between RBCs and macromolecules due to:
* High levels of circulating acute phase proteins
* Increased “stickiness” of RBCs

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Causes:
* Infection
* Inflammation
* Dehydration
* Hyperviscosity
* Malignancy
* Multiple myeloma (paraproteinemia)
* Chronic liver disease
* Autoimmune conditions

MAMC-Malignancy, Autoimmune conditions, Multiple myeloma, CLD

Question 4

Polychromasia

Answer 4

Definition:
* A disorder of erythrocyte maturation.
* Applies only to Giemsa stain.

Staining Characteristics:
* Immature RBCs stain blue-gray due to retained genetic material.
* Mature RBCs stain orange.
* The blue-gray color indicates residual RNA/DNA.
* Serves as a nonspecific marker of bone marrow stress.

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Causes of Polychromasia:

1. Response to Red Cell Loss:
   
   • Hemorrhage
   • Hemolysis
2. Recovery of Marrow Function:
   
   • Iron infusion
   • Vitamin B12 replacement
   • Erythropoietin injection
   • Recovery following chemotherapy
3. Failure of Marrow to Sustain Function:
   
   • Myelofibrosis
4. Failure of RBC Quality Control:
   
   • Postsplenectomy

Question 5

Target cells

Answer 5

Definition:
* RBCs with too much membrane relative to hemoglobin (Hb) content
* Opposite of spherocytes

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Most Common Cause (M/c/c):
* Hemoglobinopathies

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Other Causes:
* Failure to remove abnormal RBCs from circulation:
* Iron deficiency
* Thalassemia
* Sickle cell anemia
* Other hemoglobin disorders
* Splenectomy

Question 6

Dimorphic red cells

Answer 6

• Presence of two morphologically distinct populations of red blood cells (often varying in size or hemoglobin content)
  Causes:
  
  1. Iron deficiency anemia — post iron transfusion
  2. Mixed deficiency anemia — Iron + Vitamin B12/folate deficiency
  3. EPO-induced erythropoiesis
  4. Delayed transfusion reaction*
  5. Myelodysplastic syndromes (MDS)**
  6. Myeloproliferative disorders*
  7. Ribavirin anemia — associated with* ringed sideroblasts

Question 7

Echinocytes

Answer 7

Liver disease
Splenectomy

Question 8

Acanthocytes

Answer 8

Liver dis
splenectomy
Renal failure

Question 9

Tear Drop Cells

Answer 9

Thalassemia
Myelofibrosis
Extramedullary haematopoesis

MET!!

Question 10

Schistiocytes

Answer 10

Fragmented RBCs

Causes:
Mechanical valves
Extracorporeal circuit
TTP/MAHA
DIC

Question 11

Blister Cells

Answer 11

Indicate Oxidative damage
* Dapsone
*Primaquine
*G6PD deficiency

Question 12

Heinz Bodies

Answer 12

Definition:
* Denatured hemoglobin (Hb)
* Marker of oxidative stress

*	Seen in RBC metabolism disorders and hemoglobinopathies
*	Rapidly cleared by splenic macrophages Causes of Heinz Bodies:

I. Oxidative Stress
* Drugs:
* Primaquine
* Quinidine

II. Unstable Hemoglobin
* Methemoglobinemia
* Alpha-thalassemia**
* Chronic liver disease**

III. Deranged RBC Metabolism
* G6PD deficiency
* Dapsone toxicity
* Bactrim (trimethoprim-sulfamethoxazole)

IV. Impaired Red Cell Clearance
* Splenectomy

5 conditions: G6pd def, Meth haemoglobinemia, Thalassemia, splenectomy, Chronic Liver disease
5 Drugs: Methylene Blue, Primaquine, Dapsone, Bactrim, Quinidine.

Question 13

Dohle bodies

Answer 13

• found in Neutrophils
• consist of ER and Ribosomes
  #seen in:
  -Infections
  -Trauma
  -Burns
  -Leukemoid reactions
  -Foll. GCSF

whenever cell turnover increases

Goat BITE

Question 14

Howell Jolly bodies

Answer 14

Erythrocytes with bits of DNA
Causes:
* Splenectomy
* Pernicious anemia
* Macrocytosis(all causes)
*corticosteroids

Question 15

Pappenheimer bodies

Answer 15

Hemosiderin containing granules
Causes:
Sideroblastic anemia
Splenectomy

Question 16

Basophilic stippling

Answer 16

They are altered Ribosomes in cytoplasm
Causes:
-Lead poisoning
-Thalassemia
-Alcohol abuse

Question 17

Leukemoid Reaction

Answer 17

Def:
Hyperproliferation of leukocytes with immature cells released into the bloodstream; WBC count may reach 30,000–50,000/µL.

Common Causes:

=> Infections:
* Pneumonia
* Tuberculosis

=> Inflammation:
* Empyema

=> Metabolic conditions:
* Diabetic ketoacidosis (DKA)

=> Ischemia of large organs:
* Liver
* Bowel
* Kidney

=> Malignancy

=> Drugs:
* Steroids
* ATRA (All-trans retinoic acid)
* G-CSF (Granulocyte-colony stimulating factor)

=> Hematologic conditions:
* Myeloproliferative disorders
* Myeloid leukemia

Question 18

Leukoerythroblastic Picture

Left Shift

Toxic changes

Answer 18

= Definition: Presence of: immature forms of cells of myeloid series
- Granulocytic left shift (immature granulocytes eg- band cells)
-Nucleated red blood cells (RBCs) on the same blood film
=>Causes:
Bone marrow stress:
* Sepsis;Haemorrhage;Haemolysis;severe anemia;Inflammation; G-CSF
* Malignancies: Leukemia; myeloproliferative disorders
* Myelofibrosis
* Myocardial infarction (MI)

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Left Shift
* Indicates immature granulocytes (mostly neutrophils)
* Normal band cells: 2–5%
-Any increase above this = left shift
* Suggests:
- Sepsis
- Inflammation
- burns
- Trauma
-Hemorrhage
-GCSF

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Toxic Changes
≥2 of the following 3:
1. Toxic granules → Indicate immature cells
2. Toxic vacuoles → Suggest phagocytosis
3. Döhle bodies → Remnants of endoplasmic reticulum