APPP 09: Hematopoietic Systems Flashcards
What is the normal pH of blood?
7.35-7.45
How much blood do we have?
8% body weight
- 5-6 L in males
- 4-5 L in females
What are the 3 major functions of blood?
- transportation and distribution
- regulation and homeostasis
- protection and repair
What is the ‘transportation and distribution’ function of blood? (3)
- transports O2 and CO2 (respiration)
- transports nutrients and hormones
- pickup cellular and metabolic wastes for removal
What is the ‘regulation and homeostasis’ function of blood? (3)
- regulates pH
- regulates body temperature
- regulates water content of cells
What is the ‘protection and repair’ function of blood? (3)
- protects against blood loss (hemostasis)
- protects against infectious agents (inflammation)
- repairs wound and injury (wound healing)
What are the 2 components of blood?
- 45% formed elements (cellular elements)
- 55% plasma (fluid part)
What are the 3 formed elements?
- 5% platelets
- 95% red blood cells (erythrocytes)
- < 1% white blood cells (leukocytes)
What are the 5 types of white blood cells?
- neutrophils
- eosinophils
- basophils
- monocytes
- lymphocytes
What are the 6 components of plasma?
- electrolytes
- 90-92% water
- 7% proteins
- wastes
- nutrients/vitamins/hormones
- gases
What are the 4 proteins in plasma?
- 55% albumins
- 38% globulins
- fibrinogen (blood coagulation component)
- complement proteins and cytokines
What are the 3 gases in plasma?
- N2
- O2
- CO2
What are platelets?
cell fragments that are used for blood clotting
What are the 3 types of granulocytes?
- neutrophils
- eosinophils
- basophils
What is fibrinogen?
clotting factor
What do red blood cells (erythrocytes) do?
carry oxygen in the blood
What are the 3 types of globulins?
- alpha
- beta
- gamma
What do white blood cells (leukocytes) do?
responsible for all immune functions in fighting infections, tissue repair, and wound healing
What do alpha globulins do?
transport lipids/metals
What do beta globulins do?
transport hormones/vitamins
What do gamma globulins do?
immunoglobulins – antibodies
Ranking of red blood cells and white blood cells by number (highest to lowest).
- erythrocytes
- platelets
- reticulocytes
- neutrophils
- lymphocytes
- monocytes
- eosinophils
- basophils
Ranking of red blood cells and white blood cells by size (largest to smallest).
*(white blood cells > red blood cells > platelets)
- monocytes
- eosinophils, basophils
- neutrophils
- lymphocytes
- reticulocytes
- erythrocytes
- platelets
What are reticulocytes?
immature RBCs released by the bone marrow that mature into final RNC after 1-2 days in the peripheral circulation
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 to years
- immune memory
What is the lifespan of neutrophils?
- 6 hours to a few days
- 1-5 days
What is the lifespan of eosinophils?
5-10 days
What is the lifespan of basophil?
a few hours to a few days
Describe the structure of erythrocytes (RBCs).
- anucleate, acidophilic cell
- also loses other organelles including most of its mitochondria
- biconcave disk (to achieve a maximum SA to cytoplasmic V ratio
- made up with hemoglobin for gas transport
What is hematocrit?
% erythrocytes in whole blood (total volume of erythrocytes relative to total volume of whole blood)
- 37-47% for women
- 42-52% for men
What is hemoglobin?
iron-carrying pigment
- normal range is age and sex-dependent
How many hemoglobins are there per RBC?
around 300 million – with a capacity to carry over 1 billion O2 molecules
Describe the structure of hemoglobin.
- made up of 4 protein helixes (2 alpha and 2 beta globin chains)
- each globin chain carries a heme molecule (porphyrin ring and Fe2+ core)
- 4 sites for cooperative binding of O2
What is cooperative binding?
oxygen binds to the heme molecule of hemoglobin in one monomer, which induces a conformational change in the other three molecules, leading to increase O2 affinity
What are the 3 factors that affect O2 binding capacity?
- hematocrit
- other gases (CO2 and CO)
- RBC diseases
What are the 4 factors that affect O2 binding affinity?
- pH and temperature
- 2,3-biphosphoglycerate
- fetal hemoglobin (δ chain instead of β chain)
- RBC diseases
Describe the process of erythropoeisis.
hormonally regulated by a negative loop
- initiated by low O2 in the body (reduced O2 carrying capacity of the blood) – ie. hypoxia, decreased O2 availability in blood, increased O2 demand from tissues, etc.
- kidneys sense the drop in [oxygen] and release the hormone erythropoietin
- erythropoietin stimulates RBC production in bone marrow – differentiation of erythroid precursor cells, iron needed for heme production, immature reticulocytes are released from bone marrow and mature in peripheral blood
- increased O2 reduces erythropoietin production in kidney (negative feedback)
What are synthetic versions of erythropoietin (ie. EPOGEN) indicated in?
anemia – due to chronic kidney diseases
What are the 2 types of erythrocyte disorders?
- anemia
- polycythemia
What is anemia?
insufficient number of RBC (low hematocrits)
- decrease production of RBC – aplastic anemia, iron-deficient anemia
- increase turnover of RBC – abnormal hemoglobins
What is alpha and beta thalassemias?
defects in the production of the respective hemoglobins
What is sickle cell anemia?
- HbS instead of HbA
- sickle shape in hypoxic conditions
What is polycythemia?
overproduction of RBC (high hematocrits)
- increase production of RBC – abnormalities in RBC production cause an increase in red cell count
What is secondary polycythemia?
polycythemia as a result of factors external to RBC production (ie. hypoxia, sleep apnea, certain tumours)
What are the 2 types of agranulocytes?
- lymphocyte
- monocyte
Do granulocytes have a nucleus?
yes – polynucleated (more than one nucleus)
What are granulocytes activated through?
binding of ligands to cell surface receptors (including toll-like, cytokines and immunoglobulins)
- ready to detect cues in the environment
What is released once granulocytes are activated?
cytoplasmic granules of inflammatory cytokines
- contain different cytotoxic molecules
What is the most common/abundant white blood cell?
neutrophils
What are neutrophils?
mobile first responders to injury/danger
- within minutes of insult/injury
- follow chemokine gradients
What do neutrophils do?
amplify response with cytokines
- secrete cytokines
- recruit and activate other immune cells
How are neutrophils eliminated?
through apoptosis – shortly afeter activation
What are the 3 killing mechanisms of neutrophils?
- phagocytosis
- degranulation (cytotoxic molecules)
- neutrophil extracellular traps (NETs)
What is phagocytosis?
activation by pathogen-associated molecular patterns (PAMPS)
What is degranulation?
release of soluble anti-microbials and lytic enzymes
What are neutrophil extracellular traps (NETs)?
special extracellular matrix
How many eosinophils are in the blood?
- 100-400/ul (100-400k/mL) blood
- counts increase with disease association – asthma and allergies, rheumatoid arthritis, Hodgkin’s disease and Addison’s disease
What are the 2 functions of eosinophils?
release granule contents, including:
- release enzymes and cytokines to damage the infectious organism while creating localized tissue damage
- amplify the immune responses with the release of interleukins, leukotrienes, and PGE2
What do eosinophils attack?
organisms that are too big for phagocytosis
How many eosinophilia are in the blood?
500k eosinophils/mL of blood
What cells are basophils closely related to?
mast cells
What are both basophils and mast cells associated with?
many allergic conditions
Basophils
- histamine
- serotonin
- heparin
- several proteases
- degranulation induced by IgE or IgG
Do agranulocytes have a nucleus?
yes – single nucleus
Describe the morphology of monocytes.
- bigger than all other WBC
- irregular shape
- single-lobe nucleus
- no cytoplasmic granules
Describe the morphology of lymphocytes.
- single-lobe nuclues
- no cytoplasmic granules
- cytoplasm to nucleus ratio is lower than other WBC (cytoplasmic component limit)
What do monocytes do?
can migrate out of blood circulation and reside in tissue for local patrol
- these tissue residents are responsible for presenting foreign materials to the immune systems
What are the 2 types of monocytes?
- macrophages
- dendritic cells
What are the 2 types of lymphocytes?
- natural killer cells
- T-lymphocytes and B-lymphocytes
What are natural killer cells?
- contain large granules
- lack antigen specific receptors
- roles in tumour surveillance
What are T-lymphocytes and B-lymphocytes?
cellular mediators of adaptive (acquired) immunity
- activate and respond to innate immunity – cytotoxic, specificity, generates memory, adaptable
What are the functions of T-lymphocytes and B-lymphocytes?
- eliminates pathogens and infected cells
- each lymphocyte clone recognizes only one antigen, as determined by specific antigen receptor
- generates immunological memory
What is the normal range of neutrophils in whole blood, and what makes the count higher?
- 3-7 million cells/ml
- higher with bacterial, fungal infection
What is the normal range of lymphocytes in whole blood, and what makes the count higher?
- 1.5-3 million cells/ml
- higher with viral infection
What is the normal range of monocytes in whole blood, and what makes the count higher?
- 100-700k cells/ml
- higher with fungal/viral infections
What is the normal range of eosinophils in whole blood, and what makes the count higher?
- 100-400k cells/ml
- higher with viral, parasite infections, and allergic reactions
What is the normal range of basophils in whole blood, and what makes the count higher?
- 20-50k cells/ml
- higher with allergic reactions and thyroid diseases
What are the 2 functions of thrombocytes (platelets)
- hemostasis
- participation in innate and acquired immune functions – ie. serotonin storage and release
Where do platelets originate?
in bone marrow, as fragments of megakaryocytes
Describe the morphology of platelets.
- no nucleus
- different types of cytoplasmic granules – dense granules, alpha granules
What do dense granules contain?
- serotonin
- ADP
What do alpha granules contain?
clotting factors
What activates the release of granule contents in platelets?
surface receptor binding
Describe the process of thrombopoiesis.
hormonally regulated by thrombopoietin (TPO or megakaryocyte growth and development factor)
- TPO is produced continuously by the liver (main), kidney, and bone marrow
- negative feedback pathway – TPO is bound to the surface of platelets and destroyes, then free circulating TPO concentration increases with low platelet counts to induce the production by megakaryocytes in bone marrow
Describe the process of hematopoiesis.
- mature blood cells have short lifespan and constant renewal is necessary
- hematopoiesis starts in the bone marrow
- hematopoiesis regulated by a vast network of cytokines and growth factors
- synthetic versions of growth factors used as clinical therapies
