Block 2: Histo 9/7, 9/9 - Bc & Hemtopoiesis I, Ii

Front 1

About how many liters of blood are in the body?

Back 1

4L

Front 2

What are the main components of blood?

Back 2

Cellular elements (10%) and plasma (90%)

Front 3

What is blood suspended in?

Back 3

Plasma

Front 4

When blood is collected in a RED top tube, what layers form?

Back 4

Red top has no anti-coagulant factor so:

Serum layer (liquid portion)
Blood Clot layer (blood cells and clotting factors)

Front 5

When blood is collected in a PURPLE top tube, what layers form?

Back 5

Anticoagulant factor present

Plasma layer: albumin, fibrinogen, immunoglobulins, lipoproteins, hormones, vitamins, salts (about 55%)

Buffy coat: leukocytes and platelets (about 1%)

Red blood cells: about 45%

Front 6

What is a hematocrit?

Back 6

volume of RBC's (higher in men because of testosterone)

Front 7

What does it mean when something is eosinophilic?

Back 7

Loves eosin (pink)
Eosin is acidic so binds basic things
Something eosinophilic must be basic!

Front 8

Why are red blood cells anucleated?

Back 8

Makes room for hemoglobin

Front 9

Why would a biconcave shape be favorable for RBC's?

Back 9

RBC's main role is to transport O2
A biconcave shape increases the SA/Volume ratio which allows Hg to be closer to the surface of the cell
Less distance to traverse for O2 difusion

Also allows cells to be flexible when traveling through vessels

Front 10

Describe the subatomic structure of hemoglobin. How does nomenclature vary based on whether RBC's are in the lungs or in tissues?

Back 10

Globular protein with 4 porphyrin rings with central iron atom = Heme groups (bind O2 in lungs-->oxyhemoglobin; binds CO2 in tissue-->carbaminohemoglobin)

4 globin chains: 2 alpha, 2 beta

Hemoglobin = heme + globin chains

Front 11

How does the number of WBC's compare to the number of RBC's?

Back 11

RBCs>>>>>>WBC's
~5 million ~5 thousand

Front 12

Why are WBC's considered transient?

Back 12

Not meant to stay in vasculature like RBC's are

Front 13

What are the two main categories of leukocytes? How would you differentiate between the two under a microscope?

Back 13

Granulocytes: polymorphonuclear cells (multi-lobed nucleus, but appears multiple nuclei)

Agranulocytes (mononuclear): one nucleus

Front 14

What is the order of abundance of WBC's?

Back 14

Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils

Front 15

What category of WBC do neutrophils fall under? How would you identify them under the microscope? What's their function?

Back 15

Polymorphonuclear (granular)
AKA SEGS, POLYS

Granules are "neutral" in color

Hallmark feature = 2-5 lobes in nucleus with mixed granularity

Function: phagocytosis and bacterial killing.

Upon activation, enter tissues, ingest, destroy, die (1-2 day lifespan). AKA PUS

Front 16

When are neutrophils most useful?

Back 16

For acute inflammation, ex; 48 hours after MI, polys flood into dead tissue to clean up mess

Front 17

How would you identify an eosinophil under the microscope? How long are they in circulation? What function do eosinophils play in the body?

Back 17

bi-lobed nucleus, eosin loving granules (pink) bc of MAJOR BASIC PROTEIN

Are in circulation for 2-8 hours before migrating to skin, lungs, GI tract

Phagocytosis and killing of protozoa and paraistes
Moderation of hypersensitivity allergy reactions (ex: dampening down allergic reaction in nasal mucosa or in response to adverse drug reaction)

Front 18

How would you identify a basophil under the microscope? What is their function?

Back 18

Tons of granules, can't see nucleus.

Hallmark = large metachromatic granules (purplish) that obscure irregularly-lobed nucleus

Function: exposure to allergen-->degranulation (anaphylaxis, bronchoconstriction, hives)

Front 19

What granules do basophils contain and what color do they stain?

Back 19

Heparin sulfate
Histamine
Leukotrine 3

Stain blue (basophilic, love base, blue)

Front 20

How would you identify lymphocytes under the microscope? What category of WBC do they fall under? How long are they in circulation?

Back 20

Mononuclear cells with spherical nucleus (sometimes have an indentation)

Chromatin staining is INTENSE, very scant cytoplasm (thin rim) around nucleus

Live hours to years

Front 21

How are lymphocytes different from all other WBC's?

Back 21

It's the only type that will recirculate. Goes to tissue and back to blood stream.

Front 22

What is the function of lymphocytes?

Back 22

Increase in response to viral function;

Also responsible for generating specific immune responses to specific antigens

they're the main functional cells of the immune system (B & T cells are main types)

Front 23

Briefly describe where lymphocytes are produced and mature.

Back 23

Produced in marrow
B cells mature in BM
T cells mature in Thymus
Once mature, they go to periphery

Front 24

What leukocyte would be present in chronic inflammation?

Back 24

Lymphocytes

Front 25

How would you identify a monocyte under the microscope? What is their function?

Back 25

These are least easy to ID

They are BIG, have an indented, kidney shaped nucleus and eccentrically placed

Cytoplasm is blue-grey and can have very fine granules (lysosomes)

Fn: Monocytes enter CT where they become macrophages and phagocytose, produce cytokines, antigen presentation

Front 26

What is the medical term for platelets? Do they have a nucleus? What cells do they originate from? What is their function? Lifespan?

Back 26

Thrombocytes
Anucleate
Originate from megakaryocytes (giant polyploid cells)
Fn: Promoting blood clotting
Live 7-10 Days

Front 27

What platelet granules are necessary for clotting?

Back 27

Alpha Granules
-Adhesive proteins (fibrinogen, vWF)
-Growth modulators (PGDF, TGF)
-Coagulation factors

Front 28

What changes do platelets undergo upon activation?

Back 28

MT's contract to form pseudopods, granules release contents via open canalicular system

Front 29

What is anemia? What does it results in?

Back 29

Low RBC count, decreased capacity to carry O2 (decreased Hg)

Front 30

What is polycythemia? What can cause it?Also known as?

Back 30

High RBC; AKA erythrocytosis

Can be due to low O2 tension in high altitudes (increases RBC production)

Front 31

What is iron deficiency anemia? How would you identify this disorder under the microscope?

Back 31

Decrease in number of RBC's because of low iron (due to bleeding or increased need)

RBC's become microcytic (small) and HYPOCHROMIC (RBCs are paler bc of decreased Hg)

Front 32

Describe the genetic mechanism behind sickle cell anemia.

Back 32

Single point mutation in beta-globulin gene changes glutamate to valine.

This forms HbS which polymerizes and decreases cell's flexibility in navigating BV's. Last only 10-20 days. Marrow can't make new RBCs fast enough to replace them.

Front 33

How do the clinical manifestations of carbon monoxide poisoning come about?

Back 33

CO binds to Hb 200x more tightly than oxygen
Patient presents with cherry-red skin because of color of CO-Hb complex

Front 34

Draw the membrane proteins responsible to RBC shape.

Back 34

Front 35

What is the most common form of anemia?

Back 35

Iron deficiency anemia

Front 36

Describe the molecular mechanism and clinical manifestations of hereditary spherocytosis.

Back 36

Defect or deficiency of spectrin protein
Causes spheroidal RBCs more vulnerable to destruction by spleen (get stuck in vasculature)
Results in anemia!
Some get splenectomy to tx

Front 37

What four blood antigen combinations give rise to blood types?

Back 37

A antigen
A and B antigen
B antigen
No antigen (O)

Front 38

Where does erythropoiesis occur? What happens from here? How do RBCl precursors differ from mature RBC's?

Back 38

bone marrow
mature for 5-7 days, enter periphery for 120 days, killed by reticuloendothelial cells of spleen

precursors are nucleated

Front 39

What type of cell do all hematopoeitic cells originate from?

Back 39

pluropotent hematopoietic stem cells in BM

Front 40

Where is bone marrow found? What does it consist of?

Back 40

Between trabeculae and in cavities

Consists of
Hematopoietic cords (bunches)
Stroma (reticular cells + fibers, matrix, sinusoids)

Front 41

What is yellow marrow?

Back 41

Fat in marrow; when need less marrow, replace with fat

Front 42

How do the sites of blood formation differ by age?

Back 42

In embryo, BC's arise from yolk sac mesoderm
Mid-gestation: liver and spleen are hematopoietic organs, but some hematopoiesis occurs in BM
From birth to old age, BM is primary hematopoietic organ with shift toward axial skeleton

Front 43

When looking at a bone marrow biopsy, how would you determine whether percent cellularity was abnormal?

Back 43

Normal cellularity = 100-age
Babies about 100% cellular
Old: ~20% cellular

Front 44

What do myeloid progentior cells give rise to?

Back 44

Granulocytes, Monocytes/macophages, platelets, and erythrocytes.

Front 45

What cells do lymphocytes arise from?

Back 45

Lymphoid Progenitor Cell

Front 46

What cell to lymphoid stem cells and myeloid stem cells arise from?

Back 46

Hematopoietic Stem Cell

Front 47

What role do stromal cells and GF's play in hematopoiesis? What are the clinical applications of this? Provide examples, include where GF's are manufactured.

Back 47

Stromal cells and GF's facilitate differentiation and proliefation of hematopoietic lineages.

Can use these GF's in clinic:
G-CSF (Granulocyte Colony Stimulating Factor): stimulates formation of granulocytes

GM-CSF: stimulates production of granulocytes and macrophages

M-CSF: macrophage formation

IL-3 (Interleukin): ALL myeloid cells

ALL ABOVE MADE BY STROMA

EPO (erythropoeitin): stimulates RBC formation (made in kidney)

Front 48

Describe the stages (and location) of eryhtroctye maturation. How long does this take?

Back 48

BM:
Proerthroblast
Basophilic erythroblast (busy making Hg-->blue: lots of polyribs)
Polychromatophilic erythroblast (multiple colors; losing polyribs)
Orthochromatophilic erythroblast ("correct" color; have enough Hg, start to lose nucleus)

LOSE NUCLEUS (macrophage eats extruded nuclei)
ENTER CIRCULATION AS
Reticulocyte (immature: lacks pallar)
Erythrocyte (mature)

Takes about a week.

Front 49

What is a Howell-Jolly body? When does it occur? Clinical effects?

Back 49

Nuclear fragment
Occurs if RBC leaves BM and has nuclear remnant; spleen would destroy
Most often seen post-splenectomy
Causes no problems

Front 50

Describe the nucleation of reticulocytes. How long do they exist? What occurs over this period?

Back 50

Anucleate
Mature over 2-3 days to become RBC's
Lose mitochondria, ribosomes, cytoplasmic enzymes

Front 51

What's another term for erythroblast?

Back 51

Normoblast

Front 52

What is the overall trend in RBC maturation?

Back 52

large, pale nucleus to dark, small nucleus to loss of nucleus
Increase in cytoplasm, gradual decrease in cytoplasm
cytoplasm from intense blue (lots of RNA) to gray (mix of RNA and Hg) to red (full of Hg, no RNA)

Front 53

What are azurophilic granules?

Back 53

Primary granules (lysosomes) that appear early in granulocyte development
THey're non-specific; have stuff that's found in lysosomes (lysozyme, myeolperoxidase, collegenase, acid phosphatase)

Side note:
Following are specific to neutrophils:
lactoferrin
lysozyme
collagenase
alkaline phosphatase
antibacterial proteins

Front 54

Generally describe granulocyte stages of development.

Back 54

Myeloblast-->Promyelocyte-->Myelocyte-->Specific dev't

Front 55

Describe the stages of granulocytopoiesis.

Back 55

Myeblast
Promyelocyte
Myelocyte (speckled granules)
NO MORE MITOSIS

Metamyelocyte (kidney shaped nuc)
Band (in blood)
Seg (in blood)

Front 56

What is the overall trend of granulocytopoiesis?

Back 56

dark, segmented nucleus, increasing cytoplasm
no granules to primary granules to specific granules

Front 57

Describe the stages of eospinophil development.

Back 57

Eosinophilic myeloblast
Eosinophilic promyelocyte
Eosinophilic myelocyte
Eosinophilic metamyelocyte
Mature eosinophil

Front 58

Describe the different pools of WBC's.

Back 58

Precursor pool - progenitor and precursor cells
Storage pool - immature (band) and mature cells hanging around (released in times of stress)
In periphery:
Marginating pool (WBCs hanging around BV walls)
Released into Circulating Pool
Tissue pool (death by apoptosis)

Front 59

Describe the location and maturation of lymphocytes.

Back 59

Produced in Marrow, originate from Lymphoid Stem cell (which came from hematopoietic stem cell)
Migrate to various areas:
B cells to mature in marrow
T cells to mature in thymus

Once mature, migrate to peripheral lymphoid tissues
ONLY TYPE OF WBC TO RECIRCULATE

Front 60

Describe the origin and development of platelets.

Back 60

Megakaryocytes (largest cells in BM) produce platelets by cytoplasmic fragmentation

Front 61

What is pancytopenia? How can it be caused? How would this be visible on a bone marrow aspirate?

Back 61

Low blood cell counts (RBC, WBC, platelets, Hg)
Could lack hematopoietic cells (aplastic anemia)
Could have acute leukemia (100% cellularity, i.e., 100% immature cells)

If see blast cells on peripheral smear, BM is spitting out immature cells. BAD! Leukemia!

Front 62

In a WBC differential, what is a left shift?

Back 62

Increase in bands (immaturity)