[1.1] Hematopoietic System

Covers intro to disorders in erythrocytes.

What are the functions of blood?

Transports oxygen, nutrients, carbon dioxide, etc., regulates homeostasis, and protects against blood loss and disease

What are the two components of blood?

Plasma and formed elements

What is plasma?

The fluid component of blood.

What does phagocytic mean?

The ability to eat or envelop and digest other cells or other foreign substances.

What percentage of our body weight contains whole blood?

8%

Around 55% of centrifuged blood contains what?

Plasma, a clear serous fluid.

What is the major component of plasma?

Water, making up about 91.5%.

What is the primary blood plasma protein in plasma?

Albumin

Remaining 45% of centrifuged blood acounts for what?

Formed elements

What is the major component of the formed elements?

RBCs

WBCs are primarily composed of what?

Neutrophils

What does the upper layer contain?

Plasma

What is the middle layer commonly called?

Buffy coat

What does the buffy coat correspond to?

Platelets and WBCs

What is the most gravity dependent portion of the tube in centrifuged blood?

RBCs

What do you call the fluid portion collected from whole blood, which is frozen within 8 hours of collection?

Fresh Flozen Plasma

How is fresh frozen plasma useful in a clinical setting?

Used for patients who have problems with coagulation through prevention and stopping of bleeding.

What is plasma exchange?

Transfer of plasma to another patient

What does plasma contain that is important for its clotting function?

Clotting factors

What is a cryoprecipitate?

A concentrated plasma product obtained by centrifuging thawed FFP to collect insoluble precipitate.

What are the components of cryoprecipitates?

Fibrinogen, clotting factors VIII and XIII, von Willebrand Factor, and fibronectin

What are cryoprecipitates used for?

Specific cases of coagulopathies and prevention or stopping of bleeding in low fibrinogen cases.

In what cases do patients also receive plasma alongside blood transfusion and why?

In cases of unclear bleeding, to ensure that they are receiving clotting factors.

What are the three formed elements?

RBCs (erythrocytes), WBCs (leukocytes), Platelets, (thrombocytes)

What is hematopoiesis?

The process of producing blood cells and forming formed elements.

What is a multipotent / pluripotent stem cell?

Stem cell responsible for the production of a cell.

What type of cells do multipotent cells differentiate into?

Lymphoid stem cell and myeloid stem cell

Where does the lymphoid stem cell start its development and where does it mature?

Starts development in: red bone marrow

Matures in: lymphatic tissue

What types of lymphocytes do lymphoid stem cells give rise to?

1. T lymphocyte (T cell)

2. B lymphocyte (B cell)

3. Natural Killer (NK cell)

Where is the myeloid stem cell found and where does it mature?

Found and matures in the red bone marrow.

Myeloid stem cells differentiate into?

RBCs, platelets, granulocytes and monocytes

What are the three types of granulocytes that myeloid stem cells give rise to?

1. Eosinophil aka acidophil

2. Basophil

3. Neutrophil

When does a monocyte become a macrophage?

When it enters the peripheral or interstitial area outside of BVs.

What are progenitor cells?

The intermediate differentiation of the myeloid stem cells.

What are the three types of progenitor cells, and which blood cells do they give rise to?

1. CFU-E - gives rise to RBCs

2. CFU-Meg - megakaryocyte → platelets

3. CFU-GM - granulocytes and macrophage

What is a precursor?

Immature forms of cells, usually identified by the suffix “-blast.”

What does it mean if an RBC still contains a nucleus when viewed under the miroscope?

A sign of disease, entails that the majority of the RBCs are still immature.

What are the three approved/recognized indications of stem cell therapy in the country?

1. Hematopoietic stem cell transplantation

2. Cornel resurfacing with limbal stem cells

3. Skin regeneration with epidermal stem cells

In what cases do doctors perform hematopoietic stem cell transplantation, and why?

The therapy is applied to patients with certain types of blood cancers that require killing off the bone marrow to make up for the loss.

In what cases do doctors perform corneal resurfacing with limbal stem cells, and why?

The therapy is applied to patients with damaged corneas since the cornea is avascular and cannot repair itself.

In what cases do doctors perform skin regeneration with epidermal stem cell, and why?

The therapy is applied to patients with permanent skin damage and the epidermal stem cells can be used for skin regeneration.

Enumerate the 4 hospitals in the Phillipines that can do stem cell therapy.

1. Makati Medical Center (MMC)

2. The Medical City (TMC)

3. National Kidney and Transplant Institute (NKTI)

4. Lung Center of the Philippines (LCP)

Qualifications to administer stem cell therapy?

1. PRC Board of Medicine 2nd Position Paper on Stem Cell Therapy & Related Concerns

2. For Bone Marrow Transplantation - diplomates & fellows of the PhilSHBT & PhilSPH

3. For corneal resurfacing w/ limbal stem cells - diplomates & fellows of the PhilAO

The differentiation of stem cells into the formed elements are facilitated by which proteins?

Growth factors and cytokines

What process does erythropoietin stimulate?

Erythropoiesis (RBC formation)

What process does thrombopoietin stimulate?

Thrombopoiesis (platelet formation)

What is the appearance of erythrocytes?

Biconcave disc and have an area of central clearing

Requirements for RBC production

1. Ferric ion (Fe³⁺)

2. Globin

3. Cobalamin (Vit B₁₂)

4. Erythropoietin

Lifespan of blood in the body?

120 days (approx. 3-4 months)

In the RBC life cycle, what role do macrophages play?

Remove and break down old RBC through phagocytosis and recycles it into useful components.

In the RBC life cycle, what are the products of RBC breakdown by macrophages?

Heme and globin

In the RBC life cycle, what happens to the globin component?

Further digested into amino acids and reused for protein synthesis.

In the RBC life cycle, what happens to the heme component?

Digested into biliverdin and ferric cation

In the RBC life cycle, what happens to the ferric cation?

Carried in circulation by a protein called transferrin.

In the RBC life cycle, what happens to biliverdin?

Converts into bilirubin and is excreted through the liver into the small intestine. It then becomes urobilinogen via bacteria. It is absorbed by the kidney and excreted into the urine OR becomes stercobilin.

In the RBC life cycle, what role does the liver play?

Produces a substance called hepcidin.

What is the function of hepcidin?

Blocks ferriportin, allowing the exit of ferric ions from the cells AND blocks conversion of ferrous (Fe²⁺) → ferric (Fe³⁺) ions.

Enumerate the components of hemoglobin.

4 heme rings and 4 globin chains

What are the normal hemoglobin values in males and females?

Male - 13-18 g/dL (130-180 g/L)

Female - 12-16 g/dL (120-160 g/L)

What determines the different types of hemoglobin?

The types of globin chains that make up hemoglobin.

What are the different types of hemoglobin, ranked from most to least common?

1. Type A₁ (95-98%)

2. Type A₂ (2-3%)

3. Type F (Fetal, <1%)

Enumerate the globin chains present in each type of hemoglobin.

1. Type A₁ - 2 alpha and 2 beta chains

2. Type A₂ - 2 alpha and 2 delta chains

3. Type F - 2 alpha and 2 gamma chains

Why does Type F have higher affinity to oxygen?

Since the fetus acquires its oxygen from the mother, a higher affinity to oxygen is required so it can extract oxygen from the mother’s blood across the placenta.

Each globin chain contains what?

Heme ring

In what form is the iron in heme found?

Ferrous form (Fe²⁺)

How many oxygen molecules can one ferrous iron (Fe²⁺) atom in heme bind?

1 molecule of O₂

What are the required materials for the synthesis of heme?

1. Glycine

2. Succinly CoA

3. Fe²⁺

What is methemoglobinemia?

A condition in which hemoglobin iron is oxidized from Fe²⁺ to Fe³⁺, causing high oxygen binding affinity without releasing oxygen to tissues.

What is the characteristic symptom of methemoglobinemia?

Bluish skin color

What are thalassemias?

A group of genetic disorders characterized by deficient or absent alpha or beta chains.

When viewed under the microscope, what do the RBCs of patients with thalassemia look like?

Microcytic and hypochromic

What are the characteristic symptoms of thalassemias?

• Anemia

• Hemolytic complications

• Iron overload

• Pulmonary changes

• Thrombosis

What is sickle cell disease?

It is a genetic condition affecting the hemoglobin. The normal hemoglobin A1C becomes hemoglobin S, which is an abnormal form of hemoglobin.

What is the pathophysiology of sickle cell disease?

Abnormal HbS polymerizes upon deoxygenation. The stiff RBCs adapt to the characteristic sickle-shaped cell.

What are the characteristic symptoms of sickle cell disease?

• Hemolytic anemia

• Vasculopathy (ex. ischemic stroke, pulmonary HTN, priapism)

• Vaso-occlusion – vaso-occlusive pain crises (e.g. chest)

What is anemia?

Deficiency in the oxygen-carrying capacity of blood, which is commonly a result of decreased RBC or hemoglobin.

When viewed under the microscope, what do the RBCs of patients with iron-deficiency anemia look like?

Microcytic and hypochromic

What are the causes of iron-deficiency anemia?

• Inadequate iron intake

• Increased iron requirements

• Blood loss

How is iron-deficiency anemia diagnosed?

↓ Transferrin saturation (TSAT) – indicates the available plasma Fe for tissues

↓ Ferritin – indicates iron stores

When viewed under the microscope, what do the RBCs of patients with pernicious anemia look like?

Macrocytic, megaloblastic

What causes pernicious anemia?

Deficiency of intrinsic factor for Vit. B₁₂ absorption

What is another condition in which RBCs appear megaloblastic?

Folate deficiency

What is hemolytic anemia?

Premature rupturing of RBCs

What are the causes of hemolytic anemia?

• Sickle cell anemia

• Hemolytic disease of the newborn

• G6PD deficiency

How can G6PD deficiency cause hemolytic anemia?

Subjecting the patients to oxidative stress such as reckless administration of medicine can lead to hemolytic anemia.

Describe the process of hemolytic disease of the newborn.

An Rh-negative mother carries an Rh-positive baby. Once the mother is exposed to the blood of the fetus, the mother will develop Rh antibodies in the first pregnancy.

In a second pregnancy, the already abundant antibodies will attack the Rh-positive fetus.

What is polycythemia?

A blood disorder where you have too many RBCs (erythrocytosis).

What does the RBC count measure?

Parameter that measures the number of RBCs, including as well its characteristics.

What does the hematocrit measure?

Parameter that measures the %RBCs in blood

What does the reticulocyte count measure?

% of reticulocytes (immature form of RBCs) in blood

What does the Mean Corpuscular Volume (MCV) measure?

The average RBC size

What is the formula for MCV?

$$MCV=\frac{Hct\%\cdot10}{RBCcount\left(\frac{\operatorname{mi}llions}{\operatorname{mm}^3}\right)^{}}$$

What does the Mean Cell Hemoglobin (MCH) measure?

Amount of $\frac{Hgb}{RBC}$ on average

What does the Mean Corpuscular Hemoglobin Concentration (MCHC) measure?

Hemoglobin per volume of RBCs

What does Erythrocyte Sedimentation Rate (ESR) measure?

Sedimentation rate (mm/hr) of RBCs when put in a vertical tube.

How can the slow sedimentation rate of RBCs be sped up?

Through the promotion of RBC aggregation into heavier clusters via plasma proteins such as fibrinogen and immunoglobins.

What is the normal value range of the reticulocyte count?

0.5%-1.5% of the total RBC count

What is the normal value range of MCV?

80-100 fL

What is the normal value range of MCH?

27-31 picograms/cell

What is the normal value of MCHC?

32-36 g/dL