Heme Patho pt. I

Hematologic System - functions

1. Delivery of critical substances → for cellular metabolism (oxygen, WBCs, platelets)

2. Removal of waste (creatinine, uric acid, bilirubin, etc.)

3. Defense against pathogens & injury (microorganisms)

4. Maintain acid-base balance (pH levels)

Main cellular components of blood

• 1. Plasma (~55% of blood volume)

  • 91% of plasma is water

• 2. Formed elements (~45% of blood volume)

  • RBCs (~99%) → erythrocytes

  • WBCs (~<1%) → leukocytes

  • Platelets (~<1%) → thrombocytes

1. Plasma

• Complex liquid containing a variety of elements

• Contains plasma proteins → categorized into 3 categories:

  • 1. Albumin → maintains oncotic pressure, transports hormones in drugs

  • 2. Globulins → antibodies

  • 3. Fibrinogen → helps w/ clotting

• Function:

  • Transportation, regulation (BP, pH, temp), & protection (antibodies, defense from microbes, clotting)

2. Formed elements - Erythrocytes

• Aka RBCs

• Most abundant in blood

• Disc shaped & flexible (increases surface area for gas exchange, able to fit in tiny vessels & not clot)

• Responsible for tissue oxygenation & removal of CO₂

• 100-120 day life cycle (created by bone marrow, don’t reproduce)

2. Formed elements - Leukocytes

• Aka WBCs

• Defend against infection, foreign particles, & abnormal cells (cancer)

• Assist w/ tissue repair

• Act in tissues but transported by circulation

• Bigger than RBCs

• Classified by structure (contains or lacks granules):

  • Granulocytes (neutrophiles, basophils, & eosinophils) → has granules

  • Agranulocytes (monocytes, macrophages, & lymphocytes) → lack granules

2. Formed elements - Thrombocytes

• Aka platelets

• Essential for blood coagulation & control of bleeding (1st to arrive to form plug)

• Assist w/ healing

• Aggregate when injury occurs → goes from smooth to growing legs

• Platelets = fragments

• Lifespan ~7-10 days

Lymphoid organs - spleen

• Filters the blood

  • Removes antigens

  • Removes “old” or damaged cells

  • Produces antibodies

  • Stores RBCs & platelets → during injury, spleen sends extra blood to get BP up and profuse organs

    • So ruptured spleen could lead to hemorrhage & death b/c it’s so vascularized

  • Recycles iron

Lymphoid organs - lymph nodes

• Function:

  • Remove pathogens, damaged cells, & cancer cells

  • Returns lymph fluid back to circulation

Lymphoid organs - bone marrow

• Function:

  • Hematopoiesis (creation of new blood cells)

  • Immune support

• Structure:

  • Red (active) marrow:

    • Pelvis, sternum (thymus), mandible, femur, humerus

    • Stem cells live inside red marrow

  • Yellow (inactive) marrow:

    • All other sites

Hematopoiesis

• Process of blood cells production

  • Occurs in bone marrow, liver, & spleen in fetus

  • Occurs in bone marrow (red) after birth

• All cells start out as hematopoietic stem cells (HSCs) → then they eventually become what they’re supposed to be by differentiation

  • Myeloid: RBC, platelets, granulocytes, monocytes

  • Lymphoid: B cells, T cells, NK cells

Hormone of hematopoiesis

• How does the body know how many cells to make? → hormones!

  • 1. Colony-stimuating factors (CSFs): stimulates proliferation of progenitor cells → WBC production

  • 2. Erythropoietin (EPO): produced primarily by the kidney → RBC production

  • 3. Thrombopoietin (TPO): produced in the liver → platelet production

Erythropoiesis

• RBC development

• Begins in bone marrow

  • Starts as progenitor cells → many steps occur → reticulocyte (young RBC) → erythrocytes (adult RBC)

    • Reticulocyte: good indicator of RBC activity (are we making too many? → ex. bleeding leads to elevated # of retics)

• Regulation of RBC production

  • Under control of negative feedback loop w/ erythropoietin (EPO)

  • Conditions such as hypoxia or anemia cause an increase in RBC production

Nutritional requirements for erythropoiesis

• Proteins (amino acids)

• Vitamins (B₁₂. B₆, B₂, E, & C; folic acid; pantothenic acid; niacin)

• Minerals (iron & copper)

Normal destruction of old RBCs

• Old RBCs are fragile & lose flexibility

• Aged RBCs are sequestered & destroyed by macrophages primarily in spleen → destruction occurs in liver if spleen is dysfunctional/absent

• Macrophages digest RBCs & they are excreted from the liver to intestine or bile

Hemoglobin (Hgb)

• Oxygen-carrying protein located within RBCs

• Hbg is made of 4 chains (most often 2 alpha & 2 beta chains)

  • On end of each chain is Heme (blue discs in pic) where 4 O₂ molecules total attach

• Iron is needed to form Hgb & also carry oxygen → low iron results in inability to form Hbg or carry O₂

Iron

• 1/3 of total iron in body is bound to heme (to bond O₂ to hemoglobin)

• Approx. 25mg of iron is needed for RBC production

  • Mostly obtained through recycling of iron (not from diet)

    • Small amount (1mg per day) is needed from dietary sources

  • Pregnant women require more iron (most prenatals include iron)

• Unbound free iron = toxic to human cells → leads to iron overload & liver failure, damage to heart & endocrine disorders

Clotting factors

• Blood clot is a meshwork of protein (fibrin) strands that stabilizes platelet plug

  • Fibrin strands are made by clotting system in 2 pathways:

    • Intrinsic pathway: caused by internal damage to vascular endothelium

    • Extrinsic pathway: caused by external damage of tissue

    • **Both lead to activation of Factor X (10), which leads to clot formation**

Pediatric Heme considerations

• (All marrow of infants at birth = red)

• Blood cell counts are higher than adult levels at birth

  • To prepare for trauma of birth & cutting of umbilical cord (inevitable blood loss)

  • Fetus produces excess erythropoietin to stimulate extra RBC production

Elderly Heme considerations

• Erythrocyte life span is normal but erythrocytes are replaced more slowly (anemia is more likely)

• Bone marrow cells production decreases