RED BLOOD CELLS: �Erythrocytes

01

TABLE OF CONTENTS

Shape of RBCs

Production of RBCs

Regulation of RBCs

Formation of HB, iron metabolism

03

02

04

Maturation of RBCs

Anemias

05

06

Functions of Erythrocytes

• Oxygen Transport: The primary role of red blood cells is to transport hemoglobin, which carries oxygen from the lungs to the body's tissues.
• Carbon Dioxide Transport: They contain carbonic anhydrase, an enzyme that catalyzes the reversible reaction between CO₂ and water to form carbonic acid H₂CO₃.
• Acid-Base Buffer: Hemoglobin within red blood cells acts as an important buffer, helping to maintain the body's pH balance.

SHAPE OF RBCs

1

Shape and Size of Red Blood Cells

Red blood cells are biconcave discs, which gives them a large surface area for oxygen exchange and allows them to be flexible enough to squeeze through narrow capillaries.

​

• Diameter: 7.8 µm

​

• Thickness: 2.5 µm at the thickest point, 1 µm or less at the center

​

• Volume: 90-95 µm³

RBCs and Hemoglobin Concentrations

PRODUCTION OF RBCs

2

Production of RBCs (Erythropoiesis)

The site of red blood cell production changes throughout development:

​

​

• Early Embryo: primitive, nucleated RBCs are produced in the Yolk Sac

​

• Mid-Trimester: mainly the Liver, but reasonable numbers are also produced in the Spleen and Lymph Nodes

​

• Last Month of Gestation & After Birth: Produced exclusively in Bone Marrow

​

Formation of the multiple different blood cells from the original pluripotent hematopoietic stem the bone marrow.

GENESIS �OF �RBCs

Genesis of RBCs

REGULATION OF RBCs

3

Regulation of Red Blood Cell�Production—Role of Erythropoietin

• The total mass of RBCs in the circulatory system is regulated within narrow limits, so that an adequate number of RBCs is always available to provide sufficient transport of oxygen from the lungs to the tissues, yet the cells do not become so numerous that they impede blood flow.

​

• In the normal person, about 90% of all erythropoietin is formed in the kidneys; the remainder is formed mainly in the liver.

• A person is placed in an atmosphere of low oxygen, erythropoietin begins to be formed within minutes to hours, and it reaches maximum production within 24 hours. Yet almost no new RBCs appear in the circulating blood until about 5 days later.

​

​

• The important effect of erythropoietin is to stimulate the production of proerythroblasts from hematopoietic stem cells in the bone marrow

​

Function of the erythropoietin mechanism to increase production of red blood cells when tissue oxygenation decreases.

MATURATION OF RBCs

4

Maturation of Red Blood Cells -�Requirement for Vitamin B12�(Cyanocobalamin) and Folic Acid

• Both of these are essential for the synthesis of DNA, because each in a different way is required for the formation of thymidine triphosphate, one of the essential building blocks of DNA.

​

• Therefore, lack of either vitamin B₁₂ or folic acid causes abnormal and diminished DNA and, consequently, failure of nuclear maturation and cell division.

​

• produce mainly larger than normal red cells called macrocytes, are capable of carrying oxygen normally, but their fragility causes them to have a short life.

FORMATION OF HB, IRON METABOLISM

5

Formation of Hemoglobin

• Synthesis of hemoglobin begins in the proerythroblasts and continues even into the reticulocyte stage of the red blood cells. Therefore, when reticulocytes leave the bone marrow and pass into the bloodstream, they continue to form minute quantities of hemoglobin for another day or so, until they become mature erythrocytes.

Formation of hemoglobin

Combination of Hemoglobin with Oxygen

• Oxygen does not combine with the two positive bonds of the iron in the hemoglobin molecule. Instead, it binds loosely with one of the so-called coordination bonds of the iron atom. This is an extremely loose bond, so that the combination is easily reversible.

​

• Furthermore, the oxygen does not become ionic oxygen but is carried as molecular oxygen (composed of two oxygen atoms) to the tissues

Iron Metabolism

The total quantity of iron in the body averages 4 to 5 grams:

​

• about 65% of which is in the form of hemoglobin.

​

• About 4% is in the form of myoglobin.

​

• 1% is in the form of the various heme compounds that promote intracellular oxidation.

​

• 0.1% is combined with the protein transferrin in the blood plasma.

​

• 15% to 30% is stored for later use, mainly in the reticuloendothelial system and liver parenchymal cells, principally in the form of ferritin.

Iron transport and metabolism

Anemias

6

What is Anemia?

Anemia is a condition characterized by a deficiency of hemoglobin in the blood. This can be due to:

​

• Too few red blood cells.

​

• Too little hemoglobin in the cells.

​

Some types of anemia and their physiologic causes are the following. �

Blood Loss Anemia

• After rapid hemorrhage, the body replaces the fluid portion of the plasma in 1 to 3 days; the red blood cell concentration usually returns to normal within 3 to 6 weeks.

​

• In chronic blood loss, a person frequently cannot absorb enough iron from the intestines to form hemoglobin as rapidly as it is lost. Red cells are then produced that are much smaller than normal and have too little hemoglobin inside them, giving rise to microcytic, hypochromic anemia.

Aplastic Anemia

• Bone marrow aplasia means lack of functioning bone. It can be caused by exposure to high-dose radiation, chemotherapy, or certain toxic chemicals like insecticides.

​

• Some autoimmune disorders, such as lupus, can also trigger it by causing the immune system to attack the bone marrow's stem cells.

​

• In about 50% of cases, the cause is unknown (idiopathic). This is a severe condition that can be fatal if not treated. Treatment options include blood transfusions to temporarily increase red blood cell counts or a bone marrow transplant.

Hemolytic Anemias

• Hereditarily acquired, making the cells fragile, the life span of the fragile red cell is so short that the cells are destroyed faster than they can be formed.

Hemolytic Anemias

• In hereditary spherocytosis, the red cells are very small and spherical rather than being biconcave discs.

​

• These cells cannot withstand compression forces because they do not have the normal loose, baglike cell membrane structure of the biconcave discs.

​

• On passing through the splenic pulp and some other tight vascular beds, they are easily ruptured by even slight compression.

Hemolytic Anemias

• In sickle cell anemia the cells have an abnormal type of hemoglobin called hemoglobin S, containing faulty beta chains in the hemoglobin molecule.

​

• When this hemoglobin is exposed to low concentrations of oxygen, it precipitates into long crystals inside the red blood cell.

​

• These crystals elongate the cell and give it the appearance of a sickle rather than a biconcave disc.

​

• The precipitated hemoglobin also damages the cell membrane, so that the cells become highly fragile.

Hemolytic Anemias

• In C-erythroblastosis fetalis, Rh-positive red blood cells in the fetus are attacked by antibodies from an Rh-negative mother.

​

• These antibodies make the Rh-positive cells fragile, leading to rapid rupture and causing the child to be born with serious anemia

Effects of Anemia on�Function of the Circulatory�System

1. Decreased Blood Viscosity: Blood viscosity may fall to as low as 1.5 times that of water rather than the normal value of about 3.

​

• This decreases the resistance to blood flow in the peripheral blood vessels, so that far greater than normal quantities of blood flow through the tissues and return to the heart, thereby greatly increasing cardiac output

Effects of Anemia on�Function of the Circulatory�System

2. Hypoxia: resulting from diminished transport of oxygen by the blood causes the peripheral tissue blood vessels to dilate, allowing a further increase in the return of blood to the heart and increasing the cardiac output to a still higher level-sometimes three to four times normal.

​

• greatly increased cardiac output, as well as increased pumping workload on the heart.

Effects of Anemia on�Function of the Circulatory�System

3. Increased Risk of Cardiac Failure: During exercise, which greatly increases tissue demand for oxygen, extreme tissue hypoxia results, and acute cardiac failure

Polycythemia�

• Secondary Polycythemia (physiologic polycythemia). Whenever the tissues become hypoxic because of too little oxygen in the breathed air, such as at high altitudes, or because of failure of oxygen delivery to the tissues, such as in cardiac failure, the blood-forming organs automatically produce large quantities of extra red blood cells.

Polycythemia�

• Polycythemia Vera (Erythremia). Caused by a genetic aberration in the hemocytoblastic cells that produce the blood cells.

​

• The blast cells no longer stop producing red cells when too many
• cells are already present.

​

• This causes excess production of red blood cells, It usually causes excess production of white blood cells and platelets as well.

​

• In polycythemia vera, not only does the hematocrit increase, but the total blood volume also increases, on some occasions to almost twice normal

Effects of Polycythemia on Function �of the Circulatory System

1. Increased Blood Viscosity: the entire vascular system becomes intensely engorged. In addition, many blood capillaries become plugged by the viscous blood.

​

• Increased Arterial Pressure: Increase peripheral resistance and, thereby, increase arterial pressure

​

• Cyanosis: blood passes sluggishly through the skin capillaries before entering the venous plexus, a larger than normal quantity of hemoglobin is deoxygenated. The blue color of all this deoxygenated hemoglobin masks the red color of the oxygenated hemoglobin.

​

​

PATIENT 1

A 52-year-old male presents to his general practitioner (GP) complaining of shortness of breath on exertion and fatigue, which has been worsening for the past three months. The patient reveals that his previously uninvestigated heartburn and indigestion have recently become increasingly troublesome, especially at night. This is unrelieved by over-the-counter antacids. The patient also admits to using regular ibuprofen for long-term knee pain. He denies any change in weight, bowel habit, or appetite. The patient does not smoke.

Examination: The patient is afebrile, looks pale. His heart rate is 90, regular rhythm. The GP also notes angular stomatitis. Examinations of his cardio-respiratory and abdominal systems are unremarkable.

​

Laboratory Investigations

​

• Hemoglobin: 10.1 g/dL
• Peripheral Blood Film: Shows microcytic hypochromic cells and pencil-shaped poikilocytes.
• Thyroid Stimulating Hormone (TSH): 2 mIU/L (Reference range: 0.3 – 4.25 mIU/L)

​

​

Iron Profile

​

• Serum Iron: 19 µg/dL (Reference: 55 – 160 µg/dL)
• Serum Ferritin: 10 ng/mL (Reference: 20 – 250 ng/mL)
• Total Iron Binding Capacity (TIBC): 377 µg/dL (Reference: 250 – 370 µg/dL)
• Transferrin Saturation: 10% (Reference: 20 – 50%)

Vitamin Profile

​

• Serum Vitamin B12: 200 pg/mL (Reference: 160 – 950 pg/mL)
• Serum Folate: 5 ng/mL (Reference: 2 – 10 ng/mL)
• RBC Folate: 300 ng/mL (Reference: 140 – 960 ng/mL)

​

​

Urinalysis

​

• Negative for blood, protein, and glucose.

​

​

Stool Examination

• Unremarkable.
• Negative for parasites causing anemia.

Patient Concerns

​

• The patient asked for the cause of anemia and how will be the management?

​

​

Next Steps / Management Plan

​

• The patient was referred to the Gastrointestinal (GIT) Department to identify the underlying cause of iron deficiency.

​

• Investigations requested:
• Upper gastrointestinal endoscopy.
• Helicobacter pylori antigen test in stool.

PATIENT 2

A 3-year-old girl is referred with failure to thrive. She was the first child born to her parents (who are relatives). There was no family history of note. On examination, the girl was pale, slightly icteric, with frontal skull bossing. Pulse was 110/min regular with no obvious added heart sounds. On auscultation the chest was clear. Abdominal examination revealed distension with hepatomegaly 3 cm and splenomegaly 5 cm below the costal margins.

Laboratory Investigations

​

Iron Profile

​

• Serum Iron: 70 µg/dL (Reference: 50 – 120 µg/dL)
• Serum Ferritin: 15 ng/mL (Reference: 7 – 140 ng/mL)
• Total Iron Binding Capacity (TIBC): 280 µg/dL (Reference: 250 – 370 µg/dL)
• Transferrin Saturation: 25% (Reference: 22 – 40%)

​

​

Vitamin Profile

​

• Serum Folate: 4.1 µg/L (Reference: 2 – 15 µg/L)
• Serum Vitamin B12: 270 pg/mL (Reference: 160 – 950 pg/mL)

Renal Function

​

• Sodium: 142 mmol/L (Reference: 135 – 145 mmol/L)
• Potassium: 4.8 mmol/L (Reference: 3.4 – 5.0 mmol/L)
• Creatinine: 0.5 mg/dL (Reference: 0.4 – 1.0 mg/dL)

​

​

Urinalysis

​

• Bilirubin: 38 µmol/L (Reference: 1.5 – 20 µmol/L)
• AST: 65 IU/L (Reference: 10 – 45 IU/L)
• LDH: 1584 U/L (Reference: 200 – 500 U/L)

​

Next Steps

​

• The patient is referred to the hematology clinic to order a red cell transfusion program after performing a confirmatory test (Hemoglobin electrophoresis).

​

​

Family Concerns

​

• The parents were worried about the long-term outcomes and whether it could happen again in the next child?

THANKS!

Presented By:

Mohamed Sayed

CREDITS: This presentation template was created by Slidesgo, including icons by Flaticon, infographics & images by Freepik