Lecture 3

Question 1

What is thrombopoiesis
What is the normal range for thrombocytes?
How are they produced

Answer 1

Platelets production (Normal range: 150-450 x 109/L)

Formed from Hemocytoblasts stem cells in bone marrow, then move on to become megakaryoblasts and move on to become promegakaryotes and then megakaryocytes and then the megakaryocytes form platelets by endomitotic release or fragmentation.
Megakaryocytes mature by endomitotic synchronous replication
Mature Megakaryocytes are extremely large with a single lobulated nucleus and a low nuclear:cytoplasmic ratio

Endomitotic release is a process in which a cell undergoes chromosome replication without completing mitosis, resulting in a cell with multiple copies of its genome.

Question 2

How many erythrocytes are produced daily?
Explain the process of erythropoiesis
At which stage of erythropoiesis does the cell have a red color when stained and why is it so?
What stage does the cell have a gray blue appearance in the cytoplasm when stained and why is it so?
What stage does the cell have a big nucleus and small cytoplasm?
Which stage is the cell cytoplasm intensely blue or basophilic and why is it so?

At what stage of erythropoiesis does mitosis start and when does it stop?

Which rbcs are not present in normal peripheral blood?
Which types of rbcs in the process of erythropoiesis occurs in the bone marrow and how many days does it take?
Which type of rbcs are seen in the blood and spend 120 days in the blood?
At the end of which stage is the nucleus expelled?
After the nucleus is expelled, what is the name of the cell formed?
When do reticulocytes mature into erythrocytes?
What gives reticulocytes their reticulated appearance?

Answer 2

Nucleated rbcs (precursors of rbcs or normoblasts) are not present in normal peripheral blood.(all normoblasts are nucleated red blood cells, the term “nucleated red blood cells” can also broadly refer to any red blood cell that still retains a nucleus, whether in the bone marrow or (abnormally) in the peripheral blood)

Erythropoiesis- Production of red cells
•About 10 to the power 12 new erythrocytes daily; finely regulated process.

•Mature erythrocytes are derived from stem cells (bone marrow ,BM)
•a series of mitotic divisions and maturation phases

Starts with pronormoblast (proerythroblast)
To form The early (basophilic erythroblast) and then the intermediate phase(polychromatic) which are both seen 60-80% in cell cycle
Then the late (pyknotic red blood cells ) and then reticulocytes and then red blood cells. This is the post mitotic non dividing stage

Erythropoiesis is the process of red blood cell formation. Here is a detailed outline of the stages involved:

1. Pronormoblast (Proerythroblast): This is the earliest recognizable stage in erythropoiesis. The pronormoblast is a large cell with a large nucleus and a small amount of cytoplasm.
2. Basophilic Erythroblast (Early Erythroblast): In this stage, the cell is smaller than the pronormoblast. The cytoplasm is intensely basophilic due to the high content of ribosomal RNA. Basophilic erythroblasts undergo several divisions.
3. Polychromatic Erythroblast (Intermediate Erythroblast): This stage features a mix of ribosomal RNA and hemoglobin, giving the cytoplasm a gray-blue color. These cells are still capable of division and make up about 60-80% of the cell cycle in erythropoiesis.
4. Orthochromatic Erythroblast (Late Erythroblast): The cell is smaller and the nucleus is more condensed (pyknotic). The cytoplasm now contains more hemoglobin, making it more eosinophilic. This is the last stage in which the cell contains a nucleus. At the end of this stage, the nucleus is expelled.
5. Reticulocyte: After the nucleus is expelled, the cell becomes a reticulocyte. Reticulocytes are slightly larger than mature red blood cells and still contain residual RNA, which gives them a reticulated appearance when stained. They represent the post-mitotic, non-dividing stage. (No the post-mitotic, non-dividing stage starts from the orthochromatic or pyknotic stage)
6. Mature Red Blood Cell (Erythrocyte): Reticulocytes mature into erythrocytes as they lose their residual RNA. Mature erythrocytes are biconcave, anucleate cells that function primarily to transport oxygen and carbon dioxide in the blood.

To summarize, erythropoiesis begins with a pronormoblast, progresses through various erythroblast stages (early, intermediate, and late), followed by the reticulocyte stage, and culminates in the formation of mature erythrocytes.

In erythropoiesis:

• Bone Marrow Stages (Approximately 5 Days):
  
  • The process of erythropoiesis from the pronormoblast to the reticulocyte stage occurs in the bone marrow and takes about five days. This includes the stages of pronormoblast (proerythroblast), basophilic erythroblast (early erythroblast), polychromatic erythroblast (intermediate erythroblast), and orthochromatic erythroblast (late erythroblast). Finally, the reticulocytes are released into the bloodstream.
• Lifespan of Mature Red Blood Cells (Approximately 120 Days):
  
  • Once reticulocytes enter the bloodstream, they mature into red blood cells (erythrocytes) within a day or two. Mature erythrocytes then circulate in the bloodstream for about 120 days. After this period, they are typically removed from circulation and broken down by macrophages in the spleen, liver, and bone marrow.

Question 3

What regulates erythropoiesis
What are the three sources of production of the thing that regulates erythropoiesis(we know the kidney is one of them. Mention which part of the kidney)

Answer 3

Erythropoiesis regulation: hormone Erythropoietin (EPO)

•Source of production:
•Peritubular interstitial cells of the kidney (90%), liver and other tissues (10%).

Question 4

The kidneys are the only source of erythropoietin true or false
Which part of the kidneys produce erythropoietin

Answer 4

False

Peritubular interstitial cells of the kidney (90%), liver and other tissues (10%).

Question 5

State the four main factors that promote erythropoiesis and give two examples underneath
Deficiency in any of these can be associated with abnormal Erythropoiesis (anemia)

Answer 5

Minerals/Metals:
•Iron

•Vitamins:
•Vitamin B12
•Folate
•vitamin C

•Amino acids (proteins).

•Hormones:
•Erythropoietin
•Androgens-associated with those with higher muscle mass and males(who have relatively high muscle mass) . The higher the muscle mass, the higher the need for vascularization so there’s a need to form more rbcs to supply this higher muscle mass
•Thyroxine.

Question 6

What is the major site of erythropoietin production in the fetus?
What is the site for erythropoiesis in a 2 year old and what cell type is more common

Answer 6

Erythropoietin (EPO) is primarily produced in the kidneys in adults, but the liver also plays a role in its production, particularly under certain conditions and during different stages of development. Here are the key reasons why EPO is produced in the liver:

1. Primary Site in Fetus: During fetal development, the liver is the main site of erythropoietin production. This is because the fetal kidneys are not yet fully developed and functional in producing EPO. The liver compensates by producing the necessary EPO to stimulate erythropoiesis.
2. Transition to Kidney Production: After birth, the role of EPO production gradually shifts from the liver to the kidneys. By adulthood, the kidneys become the primary site for EPO production, although the liver retains some capacity to produce EPO.

3. Compensatory Mechanism: Under conditions where the kidneys are damaged or their function is impaired (such as in chronic kidney disease), the liver can increase its production of EPO to help compensate for the reduced renal production. This helps to maintain erythropoiesis and prevent anemia.
4. Response to Hypoxia: Both the kidneys and the liver can sense low oxygen levels (hypoxia) in the blood. In response to hypoxia, the liver can upregulate the production of EPO, contributing to the overall erythropoietic response and increasing red blood cell production to enhance oxygen transport.

5. Redundancy and Backup: The production of EPO in both the kidneys and the liver provides a form of physiological redundancy. This ensures that the body can maintain adequate erythropoiesis even if one organ’s ability to produce EPO is compromised.

While the kidneys are the primary site for erythropoietin production in adults, the liver is a crucial site for EPO production during fetal development and acts as a compensatory source under conditions of renal impairment or hypoxia. This dual production system ensures robust regulation of erythropoiesis throughout different stages of life and under varying physiological conditions.

• Location: In a two-year-old, erythropoiesis primarily occurs in the bone marrow. By this age, the majority of red blood cell production has shifted from the liver and spleen (which are active in fetal development) to the bone marrow.

• Cell Type: The most prominent cell type in the bone marrow of a two-year-old is the normoblast (also known as erythroblast). These are the precursor cells that develop into mature red blood cells (RBCs).

• Erythropoiesis Location: Bone marrow.
• Prominent Cell Type: Normoblasts in the bone marrow.

Question 7

Explain the role of thyroxine and androgens in Erythropoiesis

Answer 7

Thyroxine and androgens play significant roles in the regulation of erythropoiesis:

Thyroxine, also known as T4, is a thyroid hormone that has a stimulatory effect on erythropoiesis. Its roles include:

1. Stimulation of Erythropoietin Production: Thyroxine stimulates the production of erythropoietin (EPO) in the kidneys. EPO is a crucial hormone that promotes the differentiation and proliferation of erythroid progenitor cells in the bone marrow.
2. Metabolic Rate and Oxygen Consumption: Thyroxine increases the basal metabolic rate and oxygen consumption in tissues. This creates a higher demand for oxygen transport, thereby stimulating the production of red blood cells to meet this demand.
3. Direct Effects on Bone Marrow: Thyroxine may have direct stimulatory effects on the bone marrow, enhancing the proliferation and maturation of erythroid precursor cells.

Androgens, such as testosterone, also play a critical role in erythropoiesis. Their roles include:

1. Stimulation of Erythropoietin Production: Like thyroxine, androgens can stimulate the production of erythropoietin in the kidneys, promoting erythropoiesis.
2. Direct Stimulatory Effects on Erythroid Progenitor Cells: Androgens can directly stimulate erythroid progenitor cells in the bone marrow, enhancing their proliferation and differentiation into mature red blood cells.
3. Enhanced Iron Utilization: Androgens may improve the efficiency of iron utilization for hemoglobin synthesis, thereby supporting the production of red blood cells.
4. Increased Hemoglobin Levels: Androgens contribute to higher hemoglobin levels and a greater red blood cell mass, which is one reason why men typically have higher hemoglobin levels and red blood cell counts compared to women.

• Thyroxine primarily influences erythropoiesis by increasing erythropoietin production and boosting metabolic rate and oxygen demand, which in turn stimulates red blood cell production.
• Androgens stimulate erythropoiesis both directly by acting on erythroid progenitor cells and indirectly by increasing erythropoietin production and enhancing iron utilization for hemoglobin synthesis.

Question 8

Why do people in high altitudes have higher rbc counts

Answer 8

AT HIGHER ALTITUDES THE LOWER ATMOSPHERIC PRESSHRE RSULTS IN REDUCED OXYGEN AVAILABILITY.
This hypoxia environment stimulates increase EPO PRODUCTION TO PRODUCE MORE RBCS AND ONCREASE OXYGEN TRANSPORT

Question 9

What is the normal rbc shape?
Why is it non nucleated?
What’s its size?
State the components of rbc cytoplasm

1. What is the approximate proportion of hemoglobin in the cytoplasm of a red blood cell?A. One-fourth
   B. One-third
   C. One-half
   D. One-sixth**

Answer 9

Normal red cell
•Shape: a flexible biconcave (thick at the edges,thin at the center) disc
•non-nucleated (more space for Hb)
•For efficient O2 transport.

•Size: 80 – 95fl in volume (MCV)
•lifespan ~ 120 days

•Cytoplasm composition:
•haemoglobin - one-third,
•enzymes, water, solutes, etc - one-third
•Central palor - one-third

1. What is the approximate proportion of hemoglobin in the cytoplasm of a red blood cell?

A. One-fourth
B. One-third
C. One-half
D. One-sixth

Answer: B. One-third

Explanation: Hemoglobin constitutes approximately one-third of the cytoplasm of a red blood cell.

Question 10

What is the morphology of rbcs
When stained, how do matured rbcs look like?
Which part of the rbc retains more of the stain?

Answer 10

Morphology- Stain with Romanowsky (Eosin).
•E.g. Leishman stain
•More stain at periphery cuz the peripheries are thicker than the center so the peripheries will look more reddish than the center

•When stained matured RBC’s
•Cytoplasm appear orange-red or pinkish.
•Central pallor

Question 11

How much of oxygen in the blood does Haemoglobin carry ?
What is the structure of hemoglobin?
Each heme group can bind to how many molecules of oxygen?
What is the structure of HbA ?
What about HbF?
What about HbS?
How does the sickle shape occur?

Answer 11

Haemoglobin (Hb): 4 globin chains and 4 haem groups.
•Hb A: α2β2 polypeptide chains
•Each haem group can bind to one molecule of oxygen.
•Hb carries approximately 97% of the O2 in the blood.

HbF- has two alpha globin chains and 2 gamma globin chains not 2 beta like in HbA

HbF has a higher affinity for oxygen than HbA.

HbS has two alpha globins and two mutated beta globins. It occurs when The mutation in HbS occurs in the beta chain, where a single amino acid substitution takes place: valine replaces glutamic acid at the sixth position of the beta chain.
- The notation for Hemoglobin S is α₂βS₂, indicating its two alpha and two mutant beta globin chains.

1. Sickle Cell Formation:
   
   • Under low oxygen conditions, the mutated beta chains cause the hemoglobin molecules to polymerize and form long, rigid rods.
   • This polymerization leads to the deformation of red blood cells into a sickle or crescent shape, hence the name “sickle cell.”

The polymerization of Hemoglobin S (HbS) leads to the sickle shape of red blood cells through a series of molecular and structural changes. Here’s a detailed explanation of how this process occurs:

1. Amino Acid Substitution:
   
   • The critical mutation in HbS is the substitution of valine for glutamic acid at the sixth position of the beta globin chain (β6 Glu→Val).
   • This substitution changes the surface properties of the hemoglobin molecule, introducing a hydrophobic patch.
2. Polymerization Triggered by Deoxygenation:
   
   • Under low oxygen conditions (deoxygenation), the hydrophobic valine residue on the beta chain becomes exposed.
   • The exposed hydrophobic patch on one HbS molecule can interact with a complementary site on another HbS molecule, leading to aggregation.
   • This aggregation forms long, rigid polymers of deoxygenated HbS.

3. Polymer Fiber Formation:
   
   • The polymerization of HbS molecules results in the formation of long, rigid fibers inside the red blood cell.
   • These fibers align and stack, distorting the shape of the red blood cell from its normal biconcave disc to an elongated, rigid, sickle or crescent shape.
4. Cell Membrane Distortion:
   
   • As the fibers grow, they push against the cell membrane, causing it to protrude and take on the sickle shape.
   • This distortion of the cell membrane reduces the flexibility of the red blood cells, making them less able to pass through small blood vessels.
5. Reversible and Irreversible Sickle Cells:
   
   • Initially, sickling can be reversible if the red blood cells are reoxygenated, causing the HbS polymers to disassemble and the cells to regain their normal shape.
   • However, repeated cycles of sickling and unsickling cause cumulative damage to the cell membrane, eventually leading to the formation of irreversibly sickled cells that remain rigid and deformed

Question 12

What is anemia

What’s the importance of you understanding anaemia classification?

Answer 12

Low level of Hb according to age, sex, …..
•reduced oxygen-carrying capacity.

•Global public health problem

What’s the importance of you understanding anaemia classification?
Accurate diagnosis and effective management of anaemia in patients.

It is not a disease but a symptom of an underlying problem

Question 13

What is the role of Haemoglobin in oxygen transport?
State five common symptoms and clinical manifestations of anemia

Answer 13

RBCs and their function: carrying O2 from the lungs to the body’s tissues.

•Haemoglobin and its role in O2 transport: binds to oxygen and releases it to the tissues.

Symptoms and clinical manifestations:
Fatigue
Shortness of breath
Headache
Dizziness
Exertion so chest pain and shortness of breath

Signs:
Hyperdynamic circulation (murmurs)

Pallor

Question 14

What is the classification of anemia

Answer 14

1.Morphological(FBC(MCV,MCH,etc) and blood film
2.Aetiological-underlying pathological mechanism
3.Patients clinical history -acquired,congenital,acute or chronic

Question 15

What is a male said to be anemic according to his Hb?
What about females?
What three parameters do you focus on concerning the morphological classification of anemia
What do we compare the rbc size to to know if it’s normal size?

Answer 15

Morphological
Male: Hb < 13 g/dL
Female: Hb < 12 g/dL
Pregnant women is about <11.5g/dL
1. Colour
(normochromic, hypochromic(when central pallor of rbc is more than 1/3rd of the whole cell. The normal is, it’s supposed to be 1/3rd not more than 1/3rd)
2. Shape:
(pencil cell(elliptocytes or ovalocytes), target(codocytes), tear drops(dacrocytes)
Can be ball shaped in spherocytosis or have,can have thorn like projections on their surface as seen in acanthocytes or achinocytes,can have a central mouth like or slit like area on the cell membrane as seen in stomatocytes )
3. Size
(normocytic, microcytic, macrocytic): the rbc size is compared to lymphocytes in the blood to know if it’s normocytic,microcytic or macrocytic cuz the rbc size is the same as the size of the nucleus of the lymphocytes

Question 16

Under morphological anemia, What is the MCV and MCH of microcytic hypochromic anemia?
Which diseases can you see this type of anemia in?

Answer 16

MCV <801L
MCH less than 227 pg

Iron deficiency
Thalassaemis
Anaemia of chronic disease (some
Lead poisoning (denatured RNA in red cells)
Sideroblastic anemia (some cases)

An MCV of less than 80 fL indicates microcytic anemia, which means the red blood cells are smaller than normal. The most common causes of microcytic anemia include:

1. Iron Deficiency Anemia:
   
   • The most common cause of microcytic anemia. Inadequate iron levels lead to reduced hemoglobin production, which in turn results in smaller-than-normal red blood cells.
2. Thalassemia:
   
   • A group of inherited blood disorders that affect hemoglobin production. Thalassemia can cause microcytic anemia, as the abnormal hemoglobin formation results in small red blood cells.
3. Anemia of Chronic Disease (Chronic Inflammation):
   
   • In some chronic diseases, inflammation can interfere with iron metabolism and red blood cell production, sometimes leading to microcytic anemia, although it is more commonly normocytic.
4. Sideroblastic Anemia:
   
   • A disorder where the bone marrow produces ringed sideroblasts rather than healthy red blood cells. It can be congenital or acquired (due to factors like alcohol abuse, certain drugs, or lead poisoning) and often results in microcytic anemia.
5. Lead Poisoning:
   
   • Lead interferes with various enzymatic processes involved in heme synthesis, which can lead to microcytic anemia.
6. Copper Deficiency:
   
   • Rarely, copper deficiency can impair iron metabolism and lead to microcytic anemia.

Each of these conditions affects hemoglobin synthesis or red blood cell production, leading to smaller red blood cells and an MCV of less than 80 fL.

Question 17

Under morphological anemia, What is the MCV and MCH of normocytic normochromic anemia?
Which diseases can you see this type of anemia in?

Answer 17

MCV80–100fL
MCH 27-32 pg

Diseases:
Many hemolytic anemia( exmaple is malaria,sickle cell)
Anemia of chronic diseases
After acute blood loss
Renal disease
Mixed deficiencies
Bone marrow failure(example is post chemotherapy,infiltration by carcinoma,etc)

Question 18

Under morphological anemia, What is the MCV and MCH of macrocytic anemia?
Which diseases can you see this type of anemia in?
What is MCH what is Mcv

Answer 18

MCV is more than 95fL

Diseases:
Divided into megaloblastic and non megaloblastic
Megaloblastic: vitamin B 12 or folate deficiency
Non- megaloblastic: alochol, liver disease,myelodysplasia,aplastic anemia,etc

Aplastic anemia typically causes normocytic, normochromic anemia, meaning that the red blood cells are generally of normal size and hemoglobin concentration. However, there can be instances where the anemia appears macrocytic (with a higher MCV) due to the following reasons:

• In aplastic anemia, the bone marrow fails to produce sufficient blood cells, including red blood cells, white blood cells, and platelets. As a compensatory response, the body may release immature red blood cells (reticulocytes) into the bloodstream. Reticulocytes are larger than mature red blood cells, and their presence can increase the overall MCV, making the anemia appear macrocytic.

• Patients with aplastic anemia may develop deficiencies in vitamin B12 or folate due to poor dietary intake or other factors. These deficiencies cause a disruption in DNA synthesis, leading to the production of larger red blood cells (macrocytes). This would result in macrocytic anemia.

• Some treatments for aplastic anemia, such as immunosuppressive therapy, can contribute to macrocytosis. Medications like azathioprine or methotrexate, which are sometimes used in treating aplastic anemia, can cause macrocytic anemia as a side effect.

• Aplastic anemia can be associated with Paroxysmal Nocturnal Hemoglobinuria (PNH), a condition where red blood cells are destroyed prematurely. PNH can also lead to an increase in MCV, contributing to a macrocytic picture in the context of aplastic anemia.

In summary, while aplastic anemia is typically normocytic, it can sometimes present as macrocytic due to the release of larger reticulocytes, associated vitamin deficiencies, treatment effects, or the presence of other related conditions like PNH.

Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH) are two important indices used in blood tests to evaluate red blood cells (RBCs). Here’s a brief overview of each:

• Definition: MCV measures the average volume of a red blood cell.
• Formula: MCV = (Hematocrit / RBC count) × 10
• Normal Range: Typically 80–100 femtoliters (fL).
• Clinical Significance:
  
  • Low MCV (Microcytic Anemia): May indicate iron deficiency anemia, thalassemia, or other conditions that result in smaller-than-normal RBCs.
  • High MCV (Macrocytic Anemia): May suggest vitamin B12 or folate deficiency, liver disease, or other conditions that result in larger-than-normal RBCs.

• Definition: MCH measures the average amount of hemoglobin in a red blood cell.
• Formula: MCH = (Hemoglobin / RBC count) × 10
• Normal Range: Typically 27–32 picograms per cell (pg/cell).
• Clinical Significance:
  
  • Low MCH (Hypochromic Anemia): Often associated with iron deficiency anemia or thalassemia, where RBCs have less hemoglobin than normal.
  • High MCH (Hyperchromic Anemia): Less common but may be seen in conditions with large or abnormally shaped RBCs.

• MCV helps assess the size of RBCs, indicating if they are smaller or larger than normal.
• MCH evaluates the amount of hemoglobin per RBC, providing insights into the RBC’s oxygen-carrying capacity.

Both indices are useful in diagnosing and classifying different types of anemia and other blood disorders.

Question 19

What tests do we do for anemia
What is PCV AND HOW IS IT CALCULATED
What’s the difference between PCV and RBC count

Answer 19

Tests:
Blood film comment
Serum iron studies,Vit b12 and folate levels
Hb electrophoresis (ß-thal)
Patient’s history
FBc (Hb,hematocrit and rbc indices. In health individuals,PCV=Hbx3)

Packed cell volume (PCV), also known as hematocrit (Hct), is a measure in red blood cell (RBC) indices that indicates the proportion of blood made up of red blood cells. It is expressed as a percentage. The PCV is calculated by centrifuging a blood sample to separate the red blood cells from the plasma and other components, allowing for the measurement of the volume occupied by the red blood cells.
So if PCV is 45%, it means 45% of the volume of your blood is occupied by RBCS and the 55% left consists of plasma,wbcs and platelets.
However, if your RBCS count is 5 million cells/micro liter, it means there are 5 million rbcs in ever microliter of your blood
PCV is a key parameter in the complete blood count (CBC) and is used to diagnose and monitor various medical conditions, such as anemia, dehydration, and polycythemia. High PCV levels can indicate dehydration or polycythemia, while low levels can indicate anemia or overhydration.
Imagine you have a centrifuge tube with blood that has been spun down. The red blood cells settle at the bottom, and the plasma (and other components) stays at the top:

• PCV (Volume Fraction): If the total height of the blood in the tube is 100 units, and the red blood cells occupy 45 units of that height, the PCV is 45%. This shows the proportion of the total blood volume that is made up by red blood cells.
• RBC Count (Number of Cells): If you take a small sample (say, 1 microliter) from this tube and count the number of red blood cells in it, and you find there are 5 million cells, this is your RBC count.

Question 20

How is anemia diagnostically evaluated

Answer 20

Medical history and clinical assessment
o Critical role in identifying the underlying cause of anaemia.
• Information about dietary habits, medications, past medical conditions, and family history can provide valuable clues.

Dietary habits: plant based foods and green leafy vegetables helps in erythropoiesis
Pregnancy cravings that involve clay and junk food can cause them to be anemic cuz they aren’t eating well

Medications: side effects of medications can cause hemolysis. Example is sulphuric containing meds to G6PD deficiency people can cause hemolysis

Past med: any condition that causes hemolysis
Family hx- example is sickle cell anemia

Question 21

What is anisocytosis(it’s different from poikilocytosis)

Answer 21

Anisocytosis is a condition in which there is a significant variation in the size of red blood cells (RBCs) within a blood sample. So the RBCS having different sizes.
It is often detected through a blood smear test and quantified by a parameter known as the red cell distribution width (RDW) in a complete blood count (CBC).

Anisocytosis can be associated with several underlying conditions, including:

1. Anemia:
   
   • Iron Deficiency Anemia: Commonly causes microcytic (small) RBCs.
   • Vitamin B12 or Folate Deficiency: Typically leads to macrocytic (large) RBCs.
   • Hemolytic Anemia: RBCs are destroyed faster than they are produced, leading to a mix of cell sizes.
2. Bone Marrow Disorders:
   
   • Conditions such as myelodysplastic syndromes can result in the production of RBCs of various sizes.
3. Recent Blood Transfusion:
   
   • Transfusions can introduce RBCs of different sizes from the donor.
4. Chronic Liver Disease:
   
   • Liver disease can affect the production and lifespan of RBCs, leading to anisocytosis.
5. Thalassemia:
   
   • A genetic disorder affecting hemoglobin production, often resulting in microcytic RBCs.

• Symptoms:
  
  • Symptoms of anisocytosis are often related to the underlying cause. Common symptoms include fatigue, weakness, shortness of breath, and paleness.
• Diagnosis:
  
  • Blood Smear: Microscopic examination of a blood smear can reveal the presence of RBCs of varying sizes.
  • Red Cell Distribution Width (RDW): A high RDW value on a CBC indicates greater variability in RBC size.

Treatment of anisocytosis focuses on addressing the underlying cause:

1. Nutritional Deficiencies: Supplementation with iron, vitamin B12, or folate.
2. Bone Marrow Disorders: Treatment may involve medications, blood transfusions, or bone marrow transplants.
3. Chronic Diseases: Managing the primary condition (e.g., liver disease, thalassemia).

Anisocytosis is characterized by a significant variation in the size of RBCs and is often indicative of an underlying health issue. Diagnosing the root cause is crucial for effective treatment and management of the condition.

Question 22

What is poikilocytosis

Answer 22

Having red blood cells (RBCs) of different shapes is known as poikilocytosis. This condition is characterized by the presence of abnormally shaped RBCs in the blood and is often indicative of an underlying health issue.

Poikilocytosis can be caused by various conditions, including:

1. Nutritional Deficiencies:
   
   • Iron Deficiency Anemia: Can cause irregularly shaped RBCs.
   • Vitamin B12 or Folate Deficiency: Leads to the production of abnormally shaped RBCs.
2. Hemolytic Anemia:
   
   • This condition involves the premature destruction of RBCs, leading to the release of differently shaped cells.
3. Bone Marrow Disorders:
   
   • Myelodysplastic Syndromes: These can lead to the production of abnormal RBCs.
   • Bone Marrow Infiltration: Conditions like leukemia or myelofibrosis can affect the shape of RBCs.
4. Inherited Conditions:
   
   • Sickle Cell Disease: RBCs are crescent or sickle-shaped.
   • Thalassemia: RBCs can appear irregularly shaped.
5. Liver Disease:
   
   • Chronic liver disease can alter the shape of RBCs.
6. Exposure to Toxins or Certain Medications:
   
   • Can cause the production of abnormally shaped RBCs.

Some common types of abnormally shaped RBCs include:

• Sickle Cells: Crescent or sickle-shaped, commonly seen in sickle cell disease.
• Schistocytes: Fragmented RBCs, often seen in conditions like disseminated intravascular coagulation (DIC) and hemolytic uremic syndrome.
• Elliptocytes: Oval or elongated RBCs, seen in hereditary elliptocytosis and some forms of anemia.
• Spherocytes: Sphere-shaped RBCs, often seen in hereditary spherocytosis and autoimmune hemolytic anemia.
• Target Cells: RBCs with a bullseye appearance, seen in liver disease and thalassemia.
• Teardrop Cells (Dacrocytes): Teardrop-shaped RBCs, seen in myelofibrosis and other marrow disorders.

• Blood Smear: A microscopic examination of a blood smear can reveal the presence and types of abnormally shaped RBCs.
• Complete Blood Count (CBC): May show abnormalities in other RBC indices.
• Additional Tests: Depending on the suspected underlying cause, further tests might include bone marrow biopsy, genetic testing, liver function tests, or tests for nutritional deficiencies.

Treatment for poikilocytosis focuses on addressing the underlying cause:

1. Nutritional Deficiencies: Supplementation with iron, vitamin B12, or folate.
2. Bone Marrow Disorders: Treatment may involve medications, blood transfusions, or bone marrow transplants.
3. Inherited Conditions: Management strategies specific to conditions like sickle cell disease or thalassemia.
4. Liver Disease: Managing the primary liver condition.
5. Hemolytic Anemia: Treating the underlying cause of hemolysis.

Poikilocytosis

Question 23

Where are WBCS produced?
State the two main types of WBCS and the normal range for WBCS(take note of the difference between the units for WBC and that for RBC)

Answer 23

WBCs are vital components of the immune system.

Production: in the bone marrow.
Normal leucopoiesis is essential to normal host defense.

Changes in concentration and morphology
often reflect disease processes and toxic challenge (Physiologic)

Abnormalities in production →conditions e.g leukaemia.

Classified into two broad groups:
granulocytes(neutrophils,eosinophils and basophils)
agranulocytes or mononuclear cells (lymphocytes and monocytes)

Normal total wbc counts
Adults: 4.0 – 11.0 x 10 to the power 9/L

RBC unit is 10 to the power 12/L

Question 24

What are the Chief phagocytes in the body

Answer 24

Granulocytes and monocytes

Question 25

How much of WBCS do neutrophils make up ?
How many lobes does the nucleus of a neutrophil have?
What’s the color of the neutrophil?
How many hours does it last in circulation?
What about it in the tissues

Answer 25

25-75% of WBCs
2.0 -7.0 x109/L

Nucleus: has 3 to 5 lobes
Fine reddish to violet granules in cytoplasm

Production
Circulation: 6-12 hours
Tissues: 2-4 days

Question 26

What are the functions of WBCS

Answer 26

Body’s main defense against pyogenic bacterial infections and certain fungi
Mediate acute inflammation
They are the bacteria slayers

Diff between pyogenic and pyrogenic.
Pyogenic:pus
Pyrogenic:high temperature or fever

Peripheral blood neutrophils showing both intra-neutrophilic and extracellular bacteria(arrows). (b) Neutrophil with internalised bacteria (arrow) and toxic changes (hypergranularity and vacuolation).

Question 27

How much of WBCS do eosinophils make up ?
How many lobes does the nucleus of a eosinophil have?
What’s the color ?
Which part of the tissue is it seen more in?
What are the functions of the eosinophils?

Answer 27

1.0 – 6.0% of WBCs
0.02-0.4 x109/L
Bilobed nucleus; large orange-red granules

Production
Tissues>Blood

Functions
Parasites: e.g. Schistosoma (bilharzia), asaris, hookworm
Allergic responses: Hypersensitivity e.g. asthma

Weird weird things start appearing on your skin due to aggregation of rbcs in clusters on the superficial part of the skin

Question 28

How much of WBCS do basiphils make up ?
How many lobes does the nucleus of a basophil have?
How many hours does it last in circulation?
What about it in the tissues
What is its function

Answer 28

0.0 – 1.0 % of WBCs
0.00-0.1x109/L
Bilobed nucleus
f you are given a choice between lymphocyte and basophil and are asked which one has a single-lobed (round) nucleus, you should pick lymphocyte.

Reason:

•	Lymphocytes have a single, round, or slightly oval nucleus that fills most of the cell, which is the classic example of a single-lobed nucleus.
•	Basophils, while they have a bilobed nucleus, may appear to have a single round nucleus due to the dense granules that obscure the lobes. However, their nucleus is anatomically bilobed.

Conclusion:

When distinguishing between the two, lymphocytes are the definitive choice for a cell with a single-lobed (round) nucleus.

Example of MCQ Scenarios:

•	Scenario 1: “What is the anatomical structure of a basophil’s nucleus?”
•	Correct Answer: Bilobed nucleus.
•	Scenario 2: “How does a basophil’s nucleus often appear under a light microscope due to its dense granules?”
•	Correct Answer: Single round nucleus.

Production
Circulation: 8 hours
Tissues especially skin

Functions
Mediate immediate hypersensitivity reactions:asthma, urticaria, anaphylaxis
The above are type I hypersensitivity

Type I hypersensitivity is mediated by IgE antibodies and involves the release of histamine and other mediators from mast cells and basophils.

Question 29

What is the largest leukocyte in peripheral blood?

Answer 29

Monocyte

Question 30

Wh which leukocyte has a kidney shape or horse shoe shaped nucleus?
What’s the color of its cytoplasms?

Answer 30

Usually the largest leucocyte in peripheral blood (12–20 µm).

Nucleus: Kidney shaped/ horseshoe-shaped.

Cytoplasm: abundant, stains grayish-blue

Functions
Scavengers: professional phagocytize pathogens, and dead cell debris
Chronic inflammatory conditions: syphilis, TB; Kill many types of tumour cells

Question 31

General function of lymphocytes
What are the two main types of lymphocytes?
Where do they arise from?
Where do the types of lymphocytes mature in?
State one function of each type of lymphocytes

Answer 31

General function: defend against various infections, esp. viral and chronic infections.

Types:
T cells and B cells
Both arise in Bone marrow

T cells mature in thymus and B cells mature in bone marrow
Function of T cells:
CD8+: CMI against
Intracellular organisms
CD4+: T-cell help for
Antibody production and
generation of CMI(cell mediated immunity)

Function of B cells:
Plasma cells: Humoral immunity by
generation of antibodies