APPP Flashcards - Hematopoietic System

What is the normal pH of blood?

7.35 - 7.45

How much blood do people have?

5-6 L in males

4-5 L in females

Makes up 8% of body weight

What are the 3 major functions of blood?

• Transport and distribution

• Regulation and homeostasis

• Protection and repair

How does blood help with transportation and distribution?

• Transports O2 and CO2 (respiration)

• Transports nutrients and hormones

• Pickup cellular and metabolic wastes for removal

How does blood help with regulation and homeostasis?

• Regulates pH

• Regulates body temperature

• Regulates water content of cells

How does blood help with protection and repair?

• Protects against blood loss (hemostasis)

• Protects against infectious agents (inflammation)

• Repairs wound and injury (wound healing)

What is blood made of (percentages)?

55% plasma

45% cellular/formed elements

What makes up blood plasma?

• 90-92% water

• 7% proteins

  • 55% albumin

  • 38% globulins

  • Blood coagulation components

  • Complement proteins and cytokines

• <1% other dissolved materials

  • Gases (N2, O2, CO2)

  • Nutrients

  • Wastes

  • Hormones

What makes up the cellular/formed elements portion of blood?

• Almost 95% erythrocytes (RBCs) that carry O2

• 5% platelets (cell fragments for blood clotting)

• <1% leukocytes (WBCs) responsible for all immune functions

List the formed elements of blood from smallest to largest.

1) Platelets

2) Erythrocytes

3) Reticulocytes

4) Leukocytes

• Lymphocytes

• Neutrophils

• Eosinophils and Basophils

• Monocytes

What size are platelets?

2-4 um

What size are erythrocytes?

~8 um

What size are leukocytes?

9-12 um

List the formed component from largest number to smallest number?

• Erythrocytes

• Platelets

• Reticulocytes

• Neutrophils

• Lymphocytes

• Monocytes

• Eosinophils

• Basophils

What is the lifespan of erythrocytes?

100-120 days

What is the lifespan of platelets?

5-10 days

What is the lifespan of monocytes?

Months

What is the lifespan of lymphocytes?

Hours if inactive. Years if active.

What is the lifespan of neutrophils?

6 hours - a few days

What is the lifespan of eosinophils?

5-10 days

What is the lifespan of basophils?

Few hours - few days

What are erythrocytes?

• Red blood cells.

• Anucleate, acidophilic cell. Also missing other organelles including most mitochondria.

• Biconcave disk for maximum surface area to volume ratio.

• Primarily made of hemoglobin (90-95% dry weight, ~300 million) which allows for the transport of gases.

What is the hematocrit?

% erythrocytes in the whole blood (volume erythrocytes / volume blood).

37-47% for women

42-52% for men

Describe the structure of hemoglobin.

• Made up of 4 protein chains: 2a, 2B

• Each chain carries a heme molecule consisting of a porphyrin ring and a Fe2+ core that acts as the oxygen binding site.

How does oxygen binding to hemoglobin work?

Cooperative binding so that the binding of oxygen in one monomer leads to a conformational change in the other 3 that causes increased O2 affinity.

What influences the O2 binding capacity of hemoglobin?

• Hematocrit: less blood cells means lower capacity

• Other gases: gases bind to O2 binding site, lowering capacity

• RBC diseases: damaged RBCs (like anemia) lowers capacity

What influences the O2 binding affinity of hemoglobin?

• pH and temperature: higher temperature lowers affinity

• 2,3-bisphosphoglycerate: more lowers affinity

• Fetal hemoglobin: δ chain instead of B chain

• RBC diseases

What are the five types and two categories of leukocytes?

• Granulocytes

  • Neutrophil

  • Eosinophil

  • Basophil

• Agranulocytes

  • Monocytes

  • Lymphocytes

What is unique about granulocytes?

• Polynucleated

• Activated through binding of ligands to cell surface receptors (including the toll-like receptors, cytokines, and immunoglobulins.

• Contain cytoplasmic granules of inflammatory cytokines that are released upon activation.

What is unique about neutrophils?

• Mobile first responders

  • Within minutes of insult/injury

  • Follow chemokine gradients

• Amplify inflammatory response

  • Secrete cytokines

  • Recruit and activate other immune cells

• Kill invaders

• Eliminated through apoptosis shortly after activation

What are the 3 ways neutrophils kill invaders?

Phagocytosis: activation by pathogen-associated molecular patterns (PAMPs)

Degranulation: release of soluble anti-microbials and lytic enzymes

Neutrophil Extracellular Traps (NETs): special extracellular matrix

What is unique about eosinophils?

• Attack organisms that are too big for phagocytosis

• Normal range of 100-400K / mL of blood

• Role in asthma and allergies, counts increase with rheumatoid arthritis, Hodgkin’s disease, and Addison’s disease

• Release granule contents

  • Enzymes and cytokines to damage the infectious organism while creating localized tissue damages

  • Interleukins, leukotriene, and PGE2 to amplify immune response

What is eosinophilia?

Having >500K eosinophils / mL of blood

What is unique about basophils?

• Closely related to mast cells

• Release histamine, serotonin, heparin, and several proteases

• Degranulation induced by IgE or IgG

  • FcεRI is the receptor for IgE

• Associated with many allergic conditions

What is unique about agranulocytes?

• No granules

• Single lobe nucleus

What is unique about monocytes?

• Morphology: bigger than all other WBCs, irregular shape, single-lobe nucleus, no cytoplasmic granules

• Migrate out of blood into tissue for local patrol

• These tissue residents are responsible for foreign materials to the immune system

• Types include macrophages and dendritic cells

What is unique about lymphocytes?

• Morphology: single-lobe nucleus, no cytoplasmic granules

• Cytoplasm:nucleus ratio is lower than other WBCs

• Split into 3 types: natural killer cells, T-cells, and B-cells

What is unique about natural killer cells?

• Type of lymphocyte

• Large granular morphology

• Lack antigen specific receptors

• Important roles in tumor surveillance

What is unique about T-cell and B-cells?

• Type of lymphocytes

• Cellular mediators of adaptive (acquired) immunity

  • 2 trillion lymphocytes

  • Activate and respond to innate immunity

  • Specialized and adaptive

• Functions:

  • Eliminates pathogens and infected cells

  • Each lymphocyte clone recognizes only one antigen, as determined by a specific antigen receptor

  • Generate immunological memory

What is the normal range of neutrophils in blood? What affects these levels?

3-7 million cells/mL

Higher with bacterial or fungal infection

What is the normal range of lymphocytes in blood? What affects these levels?

1.5-3 million cells/mL

Higher with viral infections

What is the normal range of monocytes in blood? What affects these levels?

100-700K cells/mL

Higher with fungal or viral infections

What is the normal range of eosinophils in blood? What affects these levels?

100-400K cells/mL

Higher with viral or parasite infections, and allergic reactions

What is the normal range of basophils in blood? What affects these levels?

20-50L cells/mL

Higher with allergic reactions and thyroid diseases

What is unique about platelets?

• Also called thrombocytes

• Originate in the bone marrow as fragments of megakaryocytes

• Have no nucleus but two types of cytoplasmic granules

  • Dense granules contain serotonin and ADP (inflammation factors)

  • Alpha granules contain clotting factors

• Activated release of granule contents by surface receptor binding

• Important functions in

  • Hemostasis, coagulation, and wound healing

  • Innate and acquired immune functions like serotonin storage and release

What is anemia?

• Insufficient number of RBCs (low hematocrit)

• Can be due to:

  • Decreased production: aplastic anemia, iron-deficient anemia

  • Increased turnover: abnormal hemoglobins

    • Alpha and beta thalassemia: defects in the production of the respective hemoglobins

    • Sickle cell anemia: HbS instead of HbA, sickle shape in hypoxic conditions

What is polycythemia?

Overproduction of RBCs (high hematocrit)

Can be due to:

• Increased production: abnormalities in RBC production cause an increase in RBC count

• Secondary polycythemia: factors external to RBC production (hypoxia, sleep apnea, certain tumours) result in polycythemia

What is leukocytosis?

Increased white blood cell count (above normal range), typically due to infection.

What is erythropoiesis? How does it work?

• The production of red blood cells.

• Initiated by low O2

• Kidney senses the drop in O2 concentrations and releases erythropoietin.

• Erythropoietin stimulates RBC production in red marrow.

• Increased O2 reduced erythropoietin production in the kidney (negative feedback system)

How does erythropoietin stimulate RBC production?

• Stimulating the differentiation of erythroid precursor cells

• Iron is needed for heme production

• Immature reticulocytes are released from the bone marrow and mature in blood

• Synthetic versions of erythropoietin are ingested in anemia due to chronic kidney disease

What is thrombopoiesis? How does it work?

• The production of platelets

• Hormonally regulated by thrombopoietin (TPO / megakaryocyte growth and development factor)

• TPO is produced continuously in the liver (main), kidney, and bone marrow

• TPO targets myeloid stem cells, cell develops into megakaryoblast, which develops into megakaryocyte, which is fragmented releasing platelets into the blood

• Negative feedback pathway: TPO is bound to the surface of platelets and destroyed. Free circulating TPO concentration increases with low platelet counts, to induce the production of megakaryocytes in the bone marrow.

What is hemopoiesis? How does it work?

• Production of new blood cells.

• Starts at the bone marrow and is regulated by a vast network of cytokines and growth factors

  • Erythropoietin (EPO)

  • Thrombopoietin (TPO)

  • Granulocyte Colony Stimulating Factor (G-CSF)

  • Granulocyte-Macrophage CSF (GM-CSF)

  • Macrophage CSF (M-CSF)

  • Interleukin-7 (IL7)

• Synthetic versions of growth factors used as clinical therapies

What cells produce erythropoietin? What is its main biological activity? What is a synthetic version?

• Kidney

• Erythrocyte formation

• Epogen

What cells produce thrombopoietin? What is its main biological activity? What is a synthetic version?

• Liver and kidney

• Production of thrombocytes

• None successful

What cells produce granulocyte colony stimulating factor? What is its main biological activity? What is a synthetic version?

• Endothelium and immune cells (macrophage + others)

• Granulocyte production

• Filgrastim

What cells produce granulocyte-macrophage colony stimulating factor? What is its main biological activity? What is a synthetic version?

• Endothelium and immune cells (macrophages, T-cells, others)

• Granulocyte and macrophage production

• Sargramostim

What cells produce macrophage colony stimulating factor? What is its main biological activity? What is a synthetic version?

• Endothelium and macrophages

• Monocytes and macrophage production

• Pre-clinical development

What is the purpose of interleukin-7?

Development of lymphocytes (T-cells and B-cells)