Red Blood Cells (Erythrocytes) and Hemoglobin

Red Blood Cells (RBC) aka Erythrocytes

• Biconcave disc shape provides a large surface area for gas exchange.
• Thin-walled to allow diffusion of gases, such as oxygen and carbon dioxide, into and out of the cell for its primary function.
• Flexible to fit through small capillaries.

Hemoglobin (hgb)

• Iron containing protein in the RBC.
• Each hgb can carry 4 oxygen molecules to the tissues.
• Each erythrocyte contains hundreds of millions of hgb proteins.

Erythropoiesis

• The kidney detects low oxygen levels in the blood.
• The kidney releases erythropoietin, a hormone that stimulates the bone marrow to increase the production of RBCs.
• This process is influenced by nutrients (protein, vitamins, and minerals) and hormones (thyroxine, corticosteroids, and testosterone).

A Reticulocyte is born

• Reticulocytes (immature red blood cells) are released into the bloodstream by the bone marrow
• Reticulocytes mature into erythrocytes in about a week.
• Erythrocytes transport oxygen to tissues and transport carbon dioxide back to the lungs.
• Erythrocytes live about 120 days.

Hemolysis (RBC Destruction)

• Old or damaged erythrocytes are taken out of circulation by the spleen.
• Enzymes in the spleen breakdown erythrocytes.
• Iron is released back into the blood stream to make new hemoglobin.
• Heme is broken down to form bilirubin, which is excreted in bile and stool.

What is Anemia?

• Anemia occurs when the body doesn't have enough healthy erythrocytes or hemoglobin, or both.

Risk Factors for Anemia

• Nutritional Deficiencies (Fe, B12, Folate deficiencies).
• Chronic Diseases (kidney disease, liver disease, IBS, autoimmune disorders).
• Medications (chemotherapy, NSAIDs, PPIs).
• Age/Sex (infants, young children, pregnancy, menstruation, elderly).
• Lifestyle (heavy alcohol consumption and smoking).

Lab values: Complete Blood Count (CBC)

• Total red blood cells x 10^6 gives the number of RBCs per liter.
• Hgb provides the amount of Hgb in blood g/dL.
• Hct is packed RBC volume; fraction of the whole blood that consists of RBC.
• MCV is the size of the RBC
• MCH is the mass of the RBC.
• MCHC is the concentration of Hgb (color).
• RBC distribution width measures the variation in RBC size and shape.
• Platelets are cells that assist clotting.
• Reticulocytes are immature RBCs.

Anemia Classifications based on RBC Size (MCV) and Color (MCHC)

• Normocytic normochromic: MCV and MCHC are normal, which can occur with acute blood loss, chronic diseases, and pregnancy.
• Microcytic hypochromic: MCV and MCHC are low; RBCs are small and pale; most common is iron deficiency.
• Megaloblastic normochromic: MCV is high and MCHC is normal; RBCs are large but have normal coloring; common causes are folate deficiency and Vitamin B12 deficiency.

Anemia Classification based on Etiologies

• Hemolytic Anemias are when RBCs are destroyed faster than they can be produced, such as in Sickle Cell anemia, thalassemia, and blood transfusion reactions.
• Hypoproliferative Anemias have decreased production of RBCs by the bone marrow; caused by cancers, pregnancy, iron deficiency, anemia of chronic disease, folate deficiency, and Vitamin B12 deficiency/Pernicious Anemia.

Clinical Manifestations of All Anemias

- Cardiopulmonary symptoms from low oxygen levels.
- Dyspnea, particularly on exertion.
- Weakness.
- Palpitations.
- Dizziness.
- Orthopnea.

• Pallor.
• Increased HR and RR.
• CBC findings: total RBCs, hgb, and hct will be low.
• Symptom severity depends on acuity and severity.

Iron Deficiency Anemia

• Pathophysiology is due to an insufficient iron intake for hemoglobin synthesis.
• This is most common type of anemia.
• Occurs due to bleeding (menstruation, perimenopausal bleeding, frequent pregnancies, or GI bleeding), poor iron absorption (gastric surgery, inflammatory bowel disorders, medications), or inadequate iron intake.

Iron Deficiency Anemia Clinical Manifestations

- typical symptoms of anemia
- Low serum ferritin and iron.
- Elevated TIBC (total iron binding capacity).
- Low hemoglobin, hematocrit, and RBCs.
- Microcytic (low MCV).
- Hypochromic (low MCHC).
- Cheilosis and glossitis.
- Restless leg syndrome (RLS).
- Pica.

Iron Deficiency Anemia Collaborative Care

• Determine and treat cause
• Oral iron supplementation
• IV iron, if needed
• Education
• Prevention
• Nutrition (high iron foods)
• Iron supplementation

Anemia of Chronic Kidney Disease (CKD)

• Caused by a disruption to the production of hormone, erythropoietin.
• Erythropoietin stimulates RBC production in the bone marrow and kidneys respond to low-oxygen levels in the blood.
• CKD impairs oxygen-sensing in kidney, reducing erythropoietin.

Anemia of CKD Clinical Manifestations

- Typical symptoms of anemia, low hemoglobin, hematocrit, and RBCs along with, normocytic (normal MCV) and normochromic (normal MCHC).

Anemia of CKD Collaborative Care

• Administer exogenous erythropoietin (SQ injection).
• Treat nutritionally related anemias with supplements.
• Blood transfusions
• Consult nutritionist and follow up with patient regarding nutrition issues.

Vitamin B12 Deficiency Anemia

• Pathophysiology: B12 is a co-factor for DNA synthesis for cell division and maturation of RBCs in the bone marrow, and myelin synthesis in neurons.
• Humans absorb vitamin B12 from the gut (fish, meat, eggs, and dairy).
• Lack of vitamin B12 results in the body being unable to make mature RBCs, and it allows breakdown of myelin sheaths of some of the body's sensory and motor nerves.
  • Pernicious anemia is due to a lack of intrinsic factor, which is secreted by gastric cells and binds with B12, traveling with it to the ileum where it is absorbed.
  • Commonly due to inadequate dietary intake or faulty absorption in the gut.

Vitamin B12/Pernicious Anemia Clinical Manifestations

- Common anemia symptoms, glossitis/cheilosis, neurological manifestations (confusion, paresthesias, poor balance, abnormal proprioception, depression, and memory loss can mimic dementia).
- Labs show low Hgb and RBCs.
- Megaloblastic and normochromic.
- Low B12 assay level.

Vit B12/Pernicious Anemia Collaborative Care

• B12 supplementation of varying routes and duration based on etiology; injections are necessary to treat Pernicious Anemia.
• Provide nutrition education
• Consider drugs that interfere with B12 absorption (alcohol, Aminosalicylic Acids/antibiotics, anticonvulsants, colchicine, and oral contraceptives).

Folate Deficiency Anemia

• Pathophysiology: Folic acid is absorbed in the gut (leafy greens, legumes, vegetables, fortified grains, and liver) and necessary for synthesis of DNA in RBCs.
• Folate deficiency results in an inabilility to make enough mature RBCs
• B12 needed to convert inactive folic acid to active form.

Folate Deficiency Anemia Clinical Manifestations

- Those common with other anemias
- Cheilosis and glossitis
- Low Hgb and RBCs.
- Megaloblastic (high MCV).
- Normochromic (normal MCHC).

• No neurological symptoms!
  • Common causes include dietary deficiency.
  • Absorption issues like in Celiac Disease.
  • Disorders that increase folic acid requirements (liver disease, chronic hemolytic anemias, and pregnancy).
• Alcohol abuse is the most the most common cause of folate deficiency anemia.

Folate Deficiency Anemia Collaborative Care

• Ensure that coexisting B12 deficiency does not also exist.
• Folic acid supplementation.
• Proper nutrition.
• Alcohol cessation
• Note drugs that interfere with folic acid absorption (alcohol, antibiotics, anti-malarials, methotrexate, estrogens/oral contraceptives, phenobarbital, and phenytoin).

Sickle Cell Anemia

• Sickle Cell Anemia is hemolytic.

Sickle Cell Anemia Pathophysiology

• Inherited genetic mutation causes abnormally shaped hgb.
• The abnormal hgb causes the RBC to change shape and become rigid when exposed to low oxygen levels (sickle.)
• Rigid, deformed RBCs adhere to endothelium and occlude blood flow, resulting in ischemia.
• Increased blood viscosity (thickness) results in slowed blood flow and can contribute to occlusion.
• Cold exposure and vasoconstriction aggravates the sickling process because it slows blood flow.
• Shortened RBC lifespan (10-14 days).

Sickle Cell Anemia Causes

• Autosomal recessive genetic abnormality.
  • Sickle Cell Disease: inherited both autosomal recessive genes from both parents; most severe form of sickle cell anemia.
  • Sickle Cell Trait: inherited one autosomal recessive gene from a parent; usually asymptomatic, just a carrier of the sickle cell gene.
• Prevalent in those of African descent.
• Sickle cell trait started as an adaptive genetic mutation and those with it do not get ill from malaria.

Sickle Cell Anemia Normal vs. Sickled Cells

• Normal RBCs: 120-day life span, normal oxygen carrying capacity, 12-14 g of Hbg per ml, and RBCs destroyed at normal rate.
• Sickled Cells: 10-40-day life span, decreased oxygen carrying capacity, 6-9 g of Hbg per ml, and RBC destroyed at an accelerated rate.

Sickle Cell Anemia Clinical Manifestations

• Common anemia symptoms, pain (often in joints, abdomen, bones and chest), jaundice, fever, delayed wound healing, increased risk of infection/respiratory infections, and sexual dysfunction.

Sickle Cell Crisis: Vasooclusive Disorder

• Severe sickling leads to blockages in micro- and macro-circulation causing tissue hypoxia, inflammation, necrosis, renal failure, blindness, liver damage/failure, stroke, pulmonary infarction, splenic infarction, and myocardial infarction.
  • Acute chest syndrome is the primary cause of death; characterized as a vicious cycle of lung infarction, inflammation, and atelectasis that cause hypoxemia and lead to pulmonary hypertension and right-sided heart failure.
  • Treatment includes support for ventilation/oxygenation (meds), PRBCS, anti-infective agents, and incentive spirometry used during crises.
  • Precipitating factors include increased needed for oxygen/hypoxemia, dehydration, cold environment, infection or environments with increased oxygen tension.

Sickle Cell Anemia Collaborative Care

• Management includes pain, oxygen administration, hydration, and rest can cause sickled cells to return to normal shape.
• Life expectancy, on average is 38 - 40 years.
  • Treatment goals are to prevent crises and minimize complications and organ dysfunction.
• Hydroxyurea increases fetal hemoglobin but is teratogenic and can cause bone marrow suppression.
• Exchange blood transfusion reduces sickled cells temporarily.
• Bone marrow transplant