Blood and Hemopoiesis Flashcards

1
Q

What are the three main components of blood plasma?

A

Making up 55% of blood volume and containing 91% water, the blood plasma is made up of proteins (~8%). They are albumin to carry fatty acids / hemoglobin, antibodies, and clotting proteins (fibrinogen)

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2
Q

What are the formed elements of the blood?

A

erythrocytes, leukocytes, and platelets. They are called this rather than “cells” because some members lack nuclei.

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3
Q

How are blood smears prepared and what do you have to remember?

A

Monolayer of blood is dried and then treated with mixture of basic and acidic dye. Remember that you are looking at an entire cell (whole-mount) not a cross section. For electron micrographs, you’ll just be looking at sections of cells.

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4
Q

What percent of blood is RBCs, and about how long are they? How long do they last in the bloodstream?

A

About 45%, they are about 7 microns. They last about 120 days before being degraded in liver or spleen

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5
Q

What is a reticulocyte?

A

A RBC that still has a stainable rER. An immature blood cell.

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6
Q

What are the two integral membrane families of RBCs?

A

Glycophorins - contains A or B antigens for blood typing (glycosylation)
Band 3 proteins - contain bicarbonate-chloride exchanger exisiting as dimer / tetramer

Both are closely linked to cytoskeleton

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7
Q

Why is Band 3 important?

A

Exchanges bicarbonate of red blood cells in the lungs. Also tethers the bilayer to the cytoskeleton via ankyrin

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8
Q

What are the important peripheral proteins of RBCs?

A

Band 4.1 and ankyrin. They, with some other proteins, link glycophorins and band 3 to the actin cytoskeleton, which allows the RBC to squeeze and be flexible with some elasticity when fitting through capillaries

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9
Q

What proteins recycle the biproducts of RBC degradation?

A

Iron - Transferrin

Heme - Albumin

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10
Q

What is anemia?

A

Loss of RBCs resulting in SOB, fatigue, lethargy (less O2). Can be caused by many factors

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11
Q

What is hereditary spherocytosis?

A

Results from a spectrin defect preventing from binding to band 4.1. RBCs are round and fragile and are thus rapidly degraded by the spleen.

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12
Q

What is sickle cell anemia?

A

Caused by single amino acid mutation of hemoglobin that produces stiff, inflexible RBCs which stick together and make circulation difficult. Patients feel pain and inflammation

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13
Q

What is erythropoietin?

A

A hormone normally secreted by the kidney which upregulates RBC production. Tumors can also cause this. Some athletes use it for performance enhancing drugs

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14
Q

What causes jaundice?

A

Skin and sclera of the eye become yellow when liver cannot degrade bilirubin (complex of heme protein and albumin) into bile

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15
Q

What defines granulocytes?

A

They are named for their dye affinity. BEN: Basophils, eosinophils, and neutrophils. They all have lobulated or irregular single nuclei, and are inactive until they enter the connective tissue by diapedesis (squeeze through the endothelial walls). They only last a few days in the blood and connective tissue, and are ALL granulated and phagocytic.

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16
Q

What are the morphology and function of PMNs (polymorphoneutrophilic leukocytes)

A

Morphology: Slightly larger than RBC, contain a 3-5 lobed singular nucleus. Cytoplasm contains granules with pink dusty background staining.
Function: They are about 60% of the WBCs, acting as first responders, they quickly meet bacterial invaders with pseudopods and store them in phagosomes, sending granules to destroy them (including free radicals and hypochlorite)

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17
Q

What are specific neutrophilic granules and how can they be identified?

A

They are most of the granules of neutrophils, and contain antibacterial proteolytic enzymes (lysozome, lactoferrin). They are smaller and less electron dense than nonspecific granules?

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18
Q

What are nonspecific granules of neutrophils?

A

Also called azurophils, they are just specialized lysosomes. They contain myeloperoxidase (for production of hypochlorite) as well as typical lysosomal enzymes and defensins (antimicrobial peptides). They are larger and can be seen in a blood smear. They fuse with the engulfed phagosome and begin acting with acid hydrolases - acid phosphatase and elastase - when the pH is low enough.

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19
Q

How do PMNs have a paracrine function?

A

Release interleukins to attract more immune cells.

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20
Q

Why do PMNs have glycogen stores?

A

To function anaerobically. They often die when fighting on the front lines and form pus.

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21
Q

What is a band neutrophil?

A

Newly produced PMNs that have elongated, non-segmented nuclei that look like bands.

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22
Q

What is the morphology and function of an eosinophil?

A

~3% of WBCs
Morphology: Usually has 2 (sometimes 3) lobes and stains eosinophilically with cytoplasmic specific granules. The granules appear electron dense and crystalloid. They do also have azurophils
Function: Anti-parasitic (i.e. worm) function. If recruited to the site of basophilic allergic response, eosinophils phagocytize antigen-antibody complexes and release granules to decrease inflammatory response of basophils

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23
Q

What do eosinophilic granules contain?

A

Antiparasitic substances, like major basic protein *=(cationic protein, neurotoxins, peroxidase, etc).
Also contain anti-inflammatories histaminase and arylsulfatase (to counteract leukotrienes). Work to antagonize basophils

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24
Q

What is the morphology of a basophil?

A

Nucleus is typically basophilic but obscured by basophilic granules. They have a poorly lobated or S-shaped basophilic nucleus. Slightly small

25
Q

What is the function of a basophil?

A

They respond to antigenic stimulating by creating an inflammatory response with their granules. Their histamines cause postcapillary venules to become leaky, and dilation of large blood vessels. PMNs are attracted and release further IL’s. Phospholipases can convert arachidonic acids in the plasma membrane to leukotrienes (longer acting inflammation). Basophils can also be phagocytic.

26
Q

What defines agranulocytes?

A

They contain singular, nonlobated nuclei. They lack specific granules, and are only active in specific organs or connective tissues. They are divided into lymphocytes and monocytes.

27
Q

What is the relative frequency and morphology of a lymphocyte?

A

Making up 30% of all WBCs, they tend to be smaller. Their nuclei stain densely and are heterochromatin rich, normally flattened / elliptical nuclei with just a thin rim of basophilic cytoplasm. They contain few organelles, although many contain free ribosomes.

28
Q

What are the classes of lymphocytes along with function?

A

They are derived from lymphoid organs. T cells are involved in cellular immunity and are the most bountiful. B cells are involved in humoral immunity and differentiate into plasma cells to produce Ig’s. T cells can also become natural kill cells and T memory cells.

29
Q

What is the morphology of a monocyte and the relative frequency?

A

They make up about 6% of the WBCs. They have a deeply indented or folded nucleus and are relatively large. Nucleus has a “lacey” or reticulated chromatin pattern. They have a much greater cytoplasm:nucleus ratio than lymphocytes, as well as many lysosomes and organelles for rapid phagocytic activity.

30
Q

What is the function of a monocyte?

A

They are the precursors of phagocytic cells, including macrophages, osteoclasts, Kupffer cells in the liver, and microglia of the brain

31
Q

What are the morphology and two relative regions of platelets (thrombocytes)?

A

They are small, anucleate, biconVEX cell fragments which circulate for 7-10 days. The central region is the granulomere which stains well with basic dye. The peripheral region is the hyalomere (glass-like) which does not stain well. Hyalomere contains the peripheral and structural zone, whereas the granulomere is the organelle zone

32
Q

What are the internal structures in the two relative regions of platelets?

A

Hyalomere - contains glycocalyx, plasma membrane, and microtubule outer circumferential ring.
Granulomere - contains vesicles and organelles important for function, including glycogen, lysosomes, canaliculi, and tubular elements

33
Q

What are the alpha, delta, and gamma granules of platelets?

A

alpha granules - promote platelet aggregation, catalyze fibrinogen to fibrin, and stimulate repair of connective tissue by releasing the mitogen PDGF (platelet derived growth factor)
delta granules - hold adhesion factors to cell walls
gamma granules - hold lysosomal granules to dissolve the clot

34
Q

What are the function of actin and myosin in clot dissolution?

A

Contract the clot by bringing ruptured vessel walls together

35
Q

What is the role of tissue-plasminogen activator in the dissolution of clots?

A

Produced by endothelial cells, it converts plasminogen to plasmin, which is a potent peptidase for dissolving clots.

36
Q

What is thrombocytopenia?

A

An abnormally low platelet count which can lead to spontaneous or unchecked bleeding

37
Q

What is the clinical application of TPA?

A

It is tissue-plasminogen activator, can dissolve clots which can cause myocardial infarction, pulmonary embolisms, strokes, etc. Very good first response for heart-attacks.

38
Q

What is a vascular sinusoid?

A

part of the red marrow, they are located in circulation between arterioles and venules in place of capillaries. They are lined by endothelium with basal lamina. They are lined with reticular cells which send reticular fibers to organize the hemopoietic compartments. Newly formed blood cells displace the reticular cells and basal lamina to pass into sinusoid lumen.

39
Q

What is the function of adventitia?

A

They are the reticular cells, which line the endothelium of vascular sinusoids with sheet-like projections and organize cells.

40
Q

What types of cells can be found in the hemopoietic compartments of vascular sinusoids?

A

developing and mature erythrocytes, mergakaryocytes, macrophages, mast cells, and adipocytes

41
Q

How does the red marrow change throughout life?

A

It naturally contains more adipocytes as one ages. In yellow marrow, adipocytes replace hemopoietic tissue. This predominates in adults but can revert to hemopoietic tissue if needed.

42
Q

What is the progenitor cell of all hemopoiesis? What marker does it express? What are the two main cell lines it gives rise to?

A

pluripotential stem cell (PPSC). Expresses CD34 surface marker. Gives rise to the multipotential myeloid stem cell (CFU-GEMM) and multipotential lymphoid stem cell (CFU-L),

43
Q

What are the cells of the myeloid line?

A

Erythroid, neutrophil / monocyte (CFU-GM), eosinophil, basophil, megakaryocyte

44
Q

What progenitor cell produces two types of cells within the same line?

A

CFU-GM, a cell of the myeloid line. Produces neutrophil (CFU-G), and monocyte (CFU-M). G stands for granulocyte.

45
Q

What cells are produced in the lymphoid line?

A

Distinct CFUs for T cell and B cells

46
Q

How long is RBC production and what triggers it?

A

Kidney releases erythropoietin hormone in response to low blood oxygen levels. Takes about 1 week.

47
Q

What are the stages of erythropoiesis?

A
  1. Pronormoblast - Large blast cell, indistinguishable from others. Multinucleolated with thin basophilic cytoplasm.
  2. Basophilic normoblast - slightly smaller, denser chromatin, thin, deeply basophilic cytoplasm because ribosomes and rough ER produce hemoglobin
  3. Polychromatophilic normoblast - chromatin increasing in density, has checkerboard appearance. Cytoplasm is often turning bluish-gray to a slight pink view.
  4. Orthochromatophilic normoblast - now half the original size, chromatin is condensed or pyknotic. Cytoplasm is eosinophilic and nucleus is extruded at this stage.
  5. Reticulocyte - RBC still has some rough ER / ribosomes remaining that will stain with azure. Occur at less than 2% frequency
48
Q

What is the last stage of mitotic activity of erythropoiesis?

A

Polychromatophilic normoblast -> checkerboard like appearance with neutral cytoplasm, somewhat condensed chromatin

49
Q

At what stage is the nucleus extruded in erythropoiesis? What is this called?

A

Orthochromatophilic normoblast - also just called “normoblast”. This ejection of the nucleus is called pyknosis.

50
Q

What controls granulopoiesis?

A

Colony secreting factors (CSFs) and IL-3 secreted by T lymphocytes.

51
Q

What are the stages of granulopoiesis?

A
  1. Myeloblast - multinucleolated euchromatic basophilic blast cell. Maybe slightly more cytoplasm than pronormoblast. No granules
  2. Promyelocyte - Elliptical euchromatic nucleus, azurophil granules are prominent and all produced at this stage
  3. Myelocyte - chromatin begins to condense and nucleus flattens, fewer azurophils than previous stage because they are diluted by mitoses. Last stage of mitotic activity. Where specific granules are produced?
  4. Metamyelocyte - Nucleus continues to become bean-shaped or indented, more specific granules appear.
  5. Band form - most seen in PMNs, nucleus is elongated and folded but unsegmented.
52
Q

What is the last mitotic stage of granulopoiesis?

A

Myelocyte - the flattened nucleus stage just before metamyelocytes develop and the indentation occurs. Remember that there is a decrease in nonspecific “azurophilic” granules at this stage since they have been diluted by mitosis.

53
Q

What regulates thrombopoiesis?

A

Regulated by thrombopoietin generated in kidneys, as well as GM-CSF (granulocyte macrophage colony secreting factor) and interleukins

54
Q

What are the stages of thrombopoiesis?

A
  1. Megakaryoblast - large basophilic blast cell with nonlobed nucleus. Undergoes endomitoses without karyokinesis or cytokinesis
  2. Megakaryocyte - massive multilobed nucleus with few organelles. Granular nucleus reflecting formation of platelet fields. Cells will form openings with epithelial cells and release platelets directly into sinusoid lumen
55
Q

How does a megakaryoblast become larger?

A

Undergoes endomitosis - cells are doubled but there is no karyokinesis or cytokinesis. This doubles the cell material to make it larger and larger but the nucleus never splits from a single lobated structure

56
Q

What is karyokinesis?

A

Splitting / dividing of replicated nucleus. compare to cytokinesis

57
Q

At what stage of granulopoiesis do the specific granules emergy?

A

Myelocyte stage. This is also the last mitotic stage, when the nucleus is flattened but not indented.

58
Q

What does pyknotic mean?

A

irreversible and incredibly dark condensation chromatin, very basophilic. In orthochromatic normoblasts