What is blood?
Formed elements (cells) + plasma
What is plasma?
Water, proteins, and solutes.
What are the major proteins in plasma?
Fibrinogen, albumin, and globulins
How many erythrocytes are in the peripheral blood of an individual?
What percent of total blood volume do red cells comprise?
Describe the shape, size, and staining of erythrocytes.
Biconcave cell with no nucleus or organelles
7-8 micrometers in diameter
What fraction of the RBC mass is hemoglobin?
What is the life span of an RBC?
120 days (approx.)
Where are red cells destroyed?
Spleen, liver, and bone marrow
What are reticulocytes?
New RBC’s from bone marrow - they complete hemoglobin synthesis and mature 1-2 days after entering circulation
What is and what causes sickle cell anemia?
Genetic alteration in the hemoglobin beta-chain. Single amino acid substitution - valine (nonpolar, hydrophobic) is substituted for glutamic acid (polar, charged, acidic). The altered hemoglobin (HbS) has different biochemical and physiological properties that produce sickling of RBC’s. Hb denatures and clusters band 3 protein, ankyrin, and spectrin.
What is the genetic defect in sickle cell anemia?
Single amino acid substitution in the hemoglobin beta-chain. Glutamic acid –> valine
Which proteins are denatured and clustered by Hb in sickle cell anemia?
band 3 protein, spectrin, and ankyrin
What systemic problems do sickled blood cells cause?
- Deformed cells have difficulty in passing through the splenic sinuses, and are trapped and removed by macrophages
- Sickle cells can adhere to capillary endothelial cells and occlude vessels
- Spleen of patients with sickle cell anemia enlarged by the sequestering of the sickle cells in the cords and sinuses
- Individuals with sickle cell disease have a shortened life span
What is hereditary spherocytosis?
- Inherited disorder
- Defects in RBC membrane (specifically membrane spectrin’s association with ankyrin and actin, which helps produce RBC biconcave shape and allows cells to change shape)
- Results in spheroidal, less deformable cells.
- These RBCs are susceptible to destruction by spleen macrophages.
What causes spherocytosis?
- Spherocytosis patients have a spectrin deficiency (only have 60-90% of the spectrin of normal individuals)
- Some spherocytosis patients have an ankyrin mutation
Why does it matter if RBCs are spheroidal?
- They are less deformable
- Their inability to alter shape results in sequestration in the splenic cords and failure to pass into splenic sinuses
- This enables destruction by splenic macrophages
- Patients then have anemia and splenomegaly (enlarged spleen)
What happens on the blood smears of spherocytosis patients?
Spherocytosis RBCs lack central pale zone in blood smears
Describe the relationship between actin, ankyrin, spectrin, and band 3 protein.
Band 3 is an integral membrane protein.
Ankyrin binds to the intracellular part of ankyrin and anchors spectrin dimers to band 3 protein.
Actin is also associated with spectrin.
What are platelets?
Cell fragments 2-5 micrometers in diameter, derived from megakaryocytes.
- Large bone marrow cell
- Megakaryocyte has platelet demarcation channels derived from the plasma membrane and continuous with the extracellular space.
What is the function of platelets?
Help with blood clotting, clot retraction, and clot dissolution. Also a source of vasoactive compounds (thromboxane A2) - derived via cyclooxygenase metabolism
What sorts of things do platelets contain?
- Alpha granules: lysosomal in character
- Dense core granules: contain serotonin, ADP, ATP, and calcium
- Numerous cytoplasmic microtubules
What happens upon activation of platelets?
Platelets change from discoid shape to a more flattened appearance with extensive ruffling of cell membrane (associated with rearrangements of cytoskeleton), microtubule redistribution, and rapid polymerization of actin into microfilaments
What are neutrophils?
Granulocytes (9-12 micrometers in diameter), with a 3 lobed nucleus (up to 5 lobes as the cell matures). First phagocytic cell to appear during inflammation.
Do neutrophils undergo mitosis?
No - terminally differentiated
What types of granules do neutrophils contain?
- Specific granules: small, with alkaline phosphatase and phagocytins (antibacterial proteins)
- Azurophilic granules: larger, with myeloperoxidase and lysozomal enzymes
What percent of white cells in blood are comprised of neutrophils?
Describe immature neutrophils (name, nucleus, lifespan).
Also called Stab/band cells. Have a horseshoe shaped nucleus. Live 6-10 hours in blood and 2-3 days in tissue.
What are basophils?
Granulocytes (10-12 micrometers in diameter) with a lobed nucleus (hard to see in blood smears).
Are basophils common in blood?
No, they occur in low numbers in blood.
What kind of granules do basophils contain?
Large basophilic granules that have hydrolytic enzymes, histamine, heparan sulfate proteoglycan, and slow reacting substance. Secrete eosinophil chemotactic factor.
What percent of white cells in blood are comprised of basophils?
0.5 - 2%