Patho Week 11 (Hematology)

What are hematopoietic stem cells?

Multipotential stem cells that give rise to all the blood cells we know

What are some properties of hematopoietic stem cells?

- Capable of self renewal

- Differentiate into progenitor cell that gives rise to colonies of cells

What do hematopoietic stem cells respond to?

Respond to the need for blood cells with growth factors (based on oxygen concentration, bleedability, clotting ability)

What is the path of creating mature blood cells starting with hematopoietic stem cells?

Hematopoietic stem cell --> progenitor cells --> precursor cells (blasts) --> mature cells

Should we see premature cells in the peripheral blood (what we draw from the vein)?

NO!! If we do see them, we can suspect something is wrong

What are the 2 major subcategories of hematopoietic stem cells?

- Lymphopoietic line (makes our B and T lymphocytes, natural killer cells)

- Multipotential cell line (create granulocytes, monocytes, erythrocytes and thrombocytes)

What are blood cells?

Any of the kinds of cells normally found circulating in the blood, including WBCs, RBCs, and platelets

Maintained within our plasma

What is hematopoiesis?

The production of all types of blood cells including formation, development, and differentiation of blood cells

What is erythropoiesis?

Specifically referring to the production of RBCs

What are the different components of blood?

- RBCs

- WBCs

- Platelets

- Plasma

What are RBCs? What is their role?

Erythrocytes

primary role is oxygen transport throughout the body

Erythrocytes are released from the bone marrow as:

How long do they circulate

Reticulocytes

Circulate for about 1-2 days

What differentiates Mature RBC from Reticulocytes

reticulocytes maintain a nucleus (have larger volume than classic RBC)

What is the average lifespan of an RBC?

120 days

What are white blood cells? What is their function?

Leukocytes, main role is to fight infection and mount the immune response

What are the 5 main types of white blood cells?

- Neutrophils

- Basophils

- Eosinophils

- Lymphocytes

- Monocytes

What are platelets?

- structure

- role

Megakaryocytes, small colorless disk-shaped cell fragment without a nucleus

Have the biggest role in stopping our bleeding, key step in primary hemostasis

Platelet function is .....

Highly dependent on what is happening in the body

How are platelets involved in hemostasis?

Platelets are a key step --> they rush to the sites of vascular injury and adhere to the injured vessel wall with the help of fibrin

What is thrombopoietin (TPO)? What does it do?

Produced by the liver, it is the main signal from our body to tell us to make platelets

Stimulates production and differentiation of platelets

What is hemoglobin?

A red protein transporter of oxygen in the blood

What does hemoglobin need for synthesis

Needs iron for synthesis --> any deficiency in iron will decrease our ability to transport oxygen throughout the body

What is the structure of hemoglobin?

4 subunits (2 alpha globin and 2 beta globin chains matched together in a 1:1 ratio)

- each containing an iron atom bound to a heme group

What is fibrin? What does it do?

Insoluble protein formed from fibrinogen during the clotting of blood

Forms a fibrous mesh that impedes the flow of blood

What are neutrophils? What kind of infections are they involved in?

First line of defense (first cells to the site of infection to begin killing the invading microbes)

Involved in bacterial infections, rheumatologic inflammation

Deficiencies in neutrophils increase the risk of....

bacterial infections!

What are eosinophils? What kind of infections are they involved in?

Implicated in numerous inflammatory processes, especially allergic

Associated with parasitic infections

What kind of WBC do we see with bacterial infections?

Neutrophils

What kind of WBC do we see with parasitic infections?

Eosinophils

What are basophils? What kind of inflammation are they involved in?

Cause allergic symptoms by release of heparin and histamine (promotes blood flow to tissues)

Can also be seen with malignant disorders

What kind of WBCs do we see with allergies?

Eosinophils and basophils

What kind of WBC do we see with malignant disorders?

Basophils

What are monocytes? What is their function?

Immature macrophages that fight off bacteria, viruses, and fungi

Once infection occurs, will mature into macrophage to help eliminate the infection

What are monocytes used for in oncology?

monitor bone marrow response

What are lymphocytes? What kind of infection are they involved in?

Type of WBC that eliminates antigens by releasing antibodies (B cells), cytotoxic granules (T cells) or signaling to other cells (helper T cells)

Associated with viral infections

What kind of WBC do we see in viral infections?

Lymphocytes

What is the difference between B and T lymphocytes?

B lymphocytes produce antibodies

T lymphocytes can either be cytotoxic or signaling cells

B lymphocytes mature in the bone marrow

T lymphocytes mature in the thymus

What are blood cell disorders?

Hematologic conditions in which there's a problem with RBCs, WBCs, or platelets

Can either be benign or malignant (cancerous)

What are the two different RBC disorders?

- Anemia (low level of RBCs)

- Polycythemia (high level of RBCs)

What are the two different platelet disorders?

- Thrombocytopenia (low level of platelets)

- Thrombocytosis (high level of platelets)

What are the two different WBC disorders?

- Leukopenia (low level of WBCs)

- Leukocytosis (high level of WBCs)

What is the most common blood disorder worldwide?

Anemia

Affects about 1/3 of the global population

What is the incidence of iron-deficiency anemia?

About 1 billion people

Anemia is more common in which populations?

- Women (menstruation)

- During pregnancy

- Children as they are developing

- Elderly (poor nutrition)

Which population has the highest incidence of iron-deficiency anemia and why?

Women in menstrual years

Due to menstruation

How does anemia affect the healthcare system and workforce?

Increases costs of medical care

Lowers a person's productivity through a decreased ability to work

What is anemia? How is it diagnosed?

Reduced circulating erythrocyte mass, diagnosed as low Hgb/Hct

What are some causes of anemia?

- Blood loss (hemorrhage)

- Increased destruction (hemolysis)

- Decreased production of RBCs

- Ineffective hematopoiesis

What are some causes of blood loss, and thus anemia?

- Menstruation

- GI bleed

- Surgical hemorrhage

- Postpartum hemorrhage

What happens with chronic anemia

The patient is able to accommodate due to the body adjusting --> do not have anemia symptoms

What are some causes of increased destruction/hemolysis that lead to anemia?

External triggers like the immune system

What are some causes of decreased production of RBCs that lead to anemia?

Issue within the bone marrow, not making as much RBCs are we should

EX. lymphomas, myeloproliferative diseases

What are some causes of ineffective hematopoiesis that lead to anemia?

Some defect within the cell/bone marrow itself, makes it unable to leave bone marrow appropriately

EX. B12 deficiency

Anemia can lead to:

Tissue hypoxia

We are not circulating oxygen to perfuse our organs like we should be

If people are living with anemia and are not hypoxic/super symptomatic, it is because of:

Adaptive measures by the body

EX. Increasing CO, respirations, etc.

What is erythropoietin? What does it stimulate

Hormone secreted by the kidney in response to hypoxia

Stimulates RBC production in the bone marrow

What is hypoxia inducible factor? What does it do?

HIF-2 is a transcription factor that regulates EPO synthesis in the kidney and liver

Plays a critical role in the regulation of intestinal iron uptake

What is hepcidin?What does it do?

Systemic iron-regulatory hormone, key regulator of the entry of iron into the circulation

HUGE factor of anemia regulation (high hepcidin --> lower ability our body has to absorb iron)

What upregulates hepcidin?

Inflammation

More inflammatory entities --> less iron absorption

What is ERFE? What does it do?

Iron-regulatory hormone that acts as an erythroid regulator after hemorrhage

Produced by erythroblasts following blood loss, mediates suppression of hepcidin (allows our body to take up more iron)

What is ERFE produced by and when?

Produced by erythroblasts following blood loss

What is RBC morphology?

Useful diagnostic information regarding the underlying cause of anemia

Can be broken down into 3 main categories:

- Microcytic

- Macrocytic

- Normocytic/abnormal shapes

What characterizes microcytic anemia?

LOW MCV

Mean Corpuscular Volume (MCV)

What characterizes macrocytic anemia?

HIGH MCV

Causes enlarged RBCs, changes the border of RBCs and affects the cytoskeleton

What anemias are microcytic?

- Iron deficiency

- Thalassemia

- Sideroblastic (associated with lead poisoning)

What anemias are macrocytic?

- Folate or B12 deficiency

- Chronic liver disease (ex. cirrhosis)

- Alcohol use

What anemias are normocytic/have abnormal shapes?

- Hereditary spherocytosis

- Sickle cell disease

- Anemia of renal disease

- Hypothyroidism

- Anemia of chronic disease

What is hemoglobin concentration?

Measures the amount of the hemoglobin molecule in a volume of blood

What is hematocrit?

Measures the volume of RBC compared to the total blood volume (RBCs and plasma)

What is the mean corpuscular volume (MCV)?

A measure of the average volume of a RBC

What is the mean corpuscular hemoglobin (MCH)?

Content (weight) of Hb of the average RBC, a reflection of hemoglobin mass inside red cells

Low can be indicative of iron deficiency

What is the red blood cell count?

How many RBCs, an erythrocyte count

What is the reticulocyte index?

How many immature RBCs seen

Generally should see 1-2% circulating in peripheral blood smear

Reticulocyte index can be increased in conditions such as:

Hemolysis

Body is compensating for the RBCs being destroyed by creating more --> will have more immature cells

Reticulocyte index can be decreased in conditions such as:

Bone marrow disease

What 2 tests do we used to determine if someone anemia or not?

Hgb/Hct

What is iron and its role in anemia?

Essential element for blood production in hemoglobin

Needed to form hemoglobin and THUS transport oxygen throughout the body

The liver stores iron as:

Ferritin

What is ferritin?

Total iron storage

Stored in the liver for about 4-6 months

What is the biggest limitation of ferritin?

It is an acute phase reactant (responds to inflammation)

If someone is having some sort of inflammation, they may have a higher ferritin response

What are some testing used for the evaluation of the etiology of anemia?

- Serum iron (measures amount of circulating iron bound to transferrin)

- Serum iron-binding capacity (TIBC, measures the blood's capacity to bind iron with transferrin)

- Transferrin saturation (measures how much transferrin is actually occupied by iron)

- Serum ferritin

- Total body iron stores

What is a normal transferrin saturation?

30%

What transferrin saturation is indicative of iron deficiency anemia?

<20%

What is serum ferritin used to diagnose

iron def anemia

What are some common symptoms of anemia?

Vary depending on the cause, common sx include:

- Fatigue

- Weakness

- Pallor (pale skin)

- Tachycardia or irregular heartbeat

- Shortness of breath (dyspnea)

- Chest pain

- Restless legs

What is a major cause of anemia?

Decreased production of hemoglobin (commonly due to iron deficiency)

What are some causes of decreased production of hemoglobin, that can lead to anemia?

- Decreased hemoglobin synthesis due to iron deficiency

- Anemia of chronic disease (ex. renal failure)

- Stem cell failure (ex. aplastic anemia)

- Myelophthisic anemia

What is myelophthisic anemia? What does it lead to?

Infiltrative process of the bone marrow, typically malignant --> leads to leukoerythroblastosis

What are the examples of myelophthisic anemia

myelofibrosis

hematologic malignancies

metastatic cancer

granulomatous disease

What is leukoerythroblastosis and when can we see it?

Production of immature granulocytes and nucleated erythrocytes due to myelophthisic anemia

When does iron deficiency anemia arise?

When the balance of iron intake, iron stores, and the body's loss of iron are insufficient to fully support production of erythrocytes

Describe iron deficiency anemia based on its RBC morphology.

Microcytic, hypochromic anemia with anisocytosis and poikilocytosis

What is anisocytosis?

Variation in RBC size

What is poikilocytosis?

Variation in RBC shape

Does reticulocytosis occur in iron-deficiency anemia?

No, there is impaired RBC production due to lack of iron --> you don't have the ingredients to make RBCs anyway so cannot have reticulocytes

Iron deficiency has impaired RBC production which causes:

Marrow erythroid hyperplasia

What are some causes of iron-deficiency anemia?

- Increased iron needs (infancy, childhood, pregnancy, lactation)

- Menstrual losses in reproductive age

- In postmenopausal women and men --> tumor or vascular lesions causing blood loss

What are specific signs and sx of blood loss that may be contributing to anemia?

- Rapid blood loss --> fall in BP and dizziness

- Gradual blood loss --> tired, SOB, pale

Anemia due to excessive bleeding results when:

Loss of RBCs exceeds production of new RBCs

What may be needed to determine a non-obvious source of bleeding in a patient you suspect has hemorrhage-induced anemia?

Stool, urine, and imaging tests