Exam 3 patho: RBC Disorders

Components of blood (4)

• Leukocytes (WBCs)

• Thrombocytes (platelets)

• Erythrocytes (RBCs)

• Plasma (carries waste that is excreted into the kidneys)

Hematopoietic system

Formation from pluripotent stem cells in BM

Function of hematopoetic system

• Transport CO2, O2, and waste

• Defense against microorganisms

• Perverse integrity of vascular system

All cells of the blood are derived from…

pluripotent stem cells of bone marrow

Progenitor cells and function

Stem cells of BM differentiate into progenitor cells, either lymphoid stem cells or myeloid stem cells

• They are mother cells responsible for the lineage of a particular cell line

Differentiation of blood cells from BM stem cells

Erythrocytes

mature RBCs

Shape of RBC

Biconcave

How many O2 can be carried by hemoglobin?

4

What does O2 bind to on a hemoglobin?

Iron center

Why do people with anemia have pale RBCs?

Bc they have low iron

Folate function in blood

Folate is needed for DNA synthesis and aids in RBC formation

Vitamin B12 function

• DNA synthesis

• Nuclear maturation

• Normal cell division

• Prevents myelin breakdown

Which of the following is responsible for RBC production?

A. Vitamin B12

B. Thrombopoietin

C. EPO

D. Intrinsic factor

C. EPO

Proerythroblasts

Immature precursor cells in the bone marrow that develop into RBCs

Reticulocyte

immature RBC that has just been released from the bone marrow into the bloodstream

What steps occur after the kidneys sense low O2 in the blood stream?

1. Release EPO

2. Tells BM to produce more RBCs

3. Reticulocyte is formed

4. Matures into RBC after 24-48 hours

What does measuring Reticulocyte levels tell you?

The index rate of RBC production

Purpose of iron and vit-B

EPO function

Signals for the BM to produce more RBCs

Where is EPO released from?

Kidneys

Hemoglobin

Oxygen carrying capacity

Hematocrit

% of RBCs in the blood

MCV (Mean Corpuscular Volume)

tells us the size of the cells

• Microcytic

• Macrocytic

MCH (Mean Corpuscular Hemoglobin)

measures the average amount of hemoglobin per RBC

MCHC (Mean Corpuscular Hemoglobin Concentration)

Measures the concentration of hemoglobin in the RBCs

• Helps assess the color of the RBCs

• Hypochromic or normochromic

Common symptoms of anemia

• **Tissue hypoxia

  • Weakness + fatigue bc of decrease O2 delivery to tissues

• Pallor

  • Look at tongue to determine (bc it will look different on everyone)

• Central NS symptoms

  • Dizziness/fainting

Acute Blood Loss Anemia

Loss of blood due to sudden bleeding bc of trauma

What % of volume loss will cause symptoms?

10-20%

Blood volume loss causes a decrease in _____ _____

Venous return

Steps that occur after BV loss, result in decrease in venous return

1. Loss of blood due to trauma

2. BP decreases, CO decreases, and central pressure decreases

3. Kidney senses decreased BP

4. RAAS system activated — conserves salt and H2O

3. SNS nerve activation

4. BVs constrict

To compensate for blood loss from ABLA

SNS activation

Megaloblastic Anemia

large RBCs due to excess cytoplasmic growth, which affects the membranes of the RBCs

• floppy membranes

2 types of megaloblastic anemia

• Pernicious anemia

• Folic acid anemia

Pernicious anemia

Anemia due to vitamin B-12 deficiency

What causes the B12 deficiency in pernicious anemia?

Decreased intrinsic factor

Causes of pernicious anemia

• Gastric/stomach disorders

• Terminal ileum disorder

• Strict vegan diet

Why do gastric/stomach disorders result in pernicious anemia?

Bc parietal cells can’t produce intrinsic factor, therefore it cannot act on B12

Symptoms of terminal ileum disorder

Chronic inflammation of the bowels

• Ex: Crohn’s

Why can terminal ileum disorders result in pernicious anemia?

Inflammation of the bowel makes it difficult to absorb B12

Why can a strict vegan diet result in pernicious anemia?

Avoiding all diary, fish, and meat —

• they are major sources of B12

• super concerned about this

Symptoms of pernicious anemia

• Changes on mucosal cells

  • e.g. could cause diarrhea

• Neurological deficits

  • Issues with vibration sensation

  • Parathesia (numbness in fingers + toes)

    • Due to demyelinisation

Why does parenthesia occur in relation to pernicious anemia?

Because B12 makes up the myelin on neurons, so the lack of myelination will affect the fingers and toes first because they are the farthest from spinal cord (require more neural transmission to get info)

Folic acid anemia

Deficiency in FA, which is required to synthesize hemoglobin

• we keep trying to synthesize RBCs, but they won’t be fully matured

Causes of folic acid anemia

• Dietary deficiency

• Malabsorption (alcohol prevents absorption)

• Drug interactions

• Pregnancy (unable to absorb FA)

  • FA deficiency can result in spinabifida

Symptoms of Folic Acid Anemia

• Usual anemia symptoms

• Mostly the symptoms as B12 deficiency

• No neurological deficits

Iron deficiency anemia

• Low Fe levels caused by:

  • decreased iron intake

  • higher demands of Fe

  • bleeding

Is Iron deficiency anemia is microcytic or macrocytic and normochromic or hypochromic?

Microcytic-hypochromic anemia

Symotoms of iron deficiency anemia

• tongue becomes really smooth

  • Bc of epithelial atrophy on the tongue

• “Spoon shaped” and brittle nails

What will labs show in Iron Deficiency Anemia (for iron, ferritin, HGB, HCT, MCV, and MCHC)?

• Iron: low

• Ferritin: low

• Hemoglobin: low

  • Low bc iron is part of hgb synthesis

• Hematocrit: low

• MCV: low

• MCHC: low

Anemia of Chronic Disease

Due to decreased RBC lifespan and decreased EPO

• Chronic disease may increase inflammation and can decrease EPO production

What can cause the decreased RBC lifespan?

• T-cell activation and production of cytokines

• Altered iron metabolism

• Renal failure patients

• Cancer

Is Anemia of Chronic Disease normochromic or hypochromic, and microcytic or macrocytic?

Normochromic and is a normal size

Reticulocyte count for Anemia of Chronic Disease

• Low Reticulocyte count bc EPO isn’t being produced

Aplastic Anemia

Suppressed BM leads to pancytopenia, and affects the whole body (pluripotent)

Pancytopenia

decreased RBC, WBC, and platelets due to:

• Radiation

• Chemo

• infection

Causes of Aplastic Anemia

• High doses of radiation therapy (XRT)

• Hematopoiesis suppressed by chemicals and toxins

• Infections

• 2/3 of cases are idiopathic — we don’t know why it’s happening

Symptoms of Aplastic Anemia

Treatments for Aplastic Anemia

• Initially require blood transfusions

• BM or stem cell therapy

• Immunosuppressive therapy

Hemolytic anemia

Premature destruction of RBCs

• Hemo- = blood

• -lytic = lysis

Causes of hemolytic anemia

• Hereditary

• Acquired

  • Mechanical trauma (metal replacement valves)

  • Transfusion rxn (mismatch blood)

  • Infections

Symptoms of HA

• Easily fatigued

• Dyspnea

• Increased rate and depth of respiration

• Jaundice

Sickle cell anemia

Inherited disorder of an abnormal hemoglobin

Sickle cell is an inherited _____ trait

Recessive trait

Sickle cell anemia point mutation

Glutamic acid is replaced with valine

What happens when the cells sickle?

Instead of biconcave shape, cells sickle → stick to wall → hemolysis → occlude vessels

Reversible sickle cells

Oxygenated RBCs are normal shaped, but when they are deoxygenated they become sickled. They can return to normal once oxygenated again

• RBCs can become irreversibly sickled

Complications of sickle cell anemia

• vaso-occlusion (wherever there is an occlusion, there will be pain)

• acute chest syndrome

• infections

Triggers for vaso-occlusive pain

• Cold weather

• Stress

• Physical exertion

Acute chest syndrome and triggers

Blocked (occluded) vessels in the lungs due to sickled RBCs, causing vaso-occlusive pain

Why are people with sickle cell anemia prone to infections?

• The spleen helps the body fight off certain bacteria

  • Spleen damage reduces the body's ability to fight off certain bacteria

Polycythemia Vera

Rare blood cancer which BM overproduces RBC, WBC, and platelets

• Opposite of Aplastic Anemia

Complications of Polycythemia Vera

• Splenomegaly (Enlargement of spleen)

• Hypertension (dizziness + headache)

• Viscosity increases — results in venous stasis

Age related issues regarding RBCs

• Anemia common in elderly

• Increases morbidity & mortality if untreated

• Usually asymptomatic in iron deficiency & chronic disease

• Stress bleeding

• RBCs not replaced as quickly

  • # progenitor cells decrease with age

  • Decrease in growth factors stimulating new cells

  • Erythropoietin issues (not as much is released/receptors may not work as well)

___% of people over 80 have anemia, and ___% if you have a chronic illness

• 25% of people >80

• 50% of people >80 and have a chronic illness