Exam 2: Walenga 1 Flashcards
Blood:
A complex fluid composed of ____& ______
Blood is considered a _______
Humans posses roughly ___ of blood in total
Blood:
A complex fluid composed of 3 cell types and plasma
Blood is considered to be a connective tissue
Humans posses roughly 5L of blood in total
Explain the three different cell types in blood:
What are they called?
Normal number for each?
What is their function?
- Erythrocytes (RBCs)
- most abundant, 5 x 106 / uL
- carry O2 via hemoglobin
- Leukocytes (WBCs)
- 5 x 103 / uL
- mediate immune response to infection and stimulate inflammation
- engulf foreing particles, antibody production
- Platelets or “thrombocytes”
- 250 x 103 / uL
- important in blood coagulation
Explain all of the components of plasma (hint there are three)
Plasma: the liquid portion of blood
Water: solvent for carrying glucose, nutrients, hormones, transporting waste products of metabolism to the kidneys and liver
Electrolytes (Na, K, HCO3, Mg, Cl): osmotic balance, pH buffering
Plasma Proteins: osmotic balance, pH buffering
- albumin
- fibrinogen and coagulation enzymes
Blood Cell Production:
_________ is a continous and highly regulated process of blood cell production that includes cell:
Renewal
Proliferation
Differentiation
Maturation
This process takes place in the ______
All blood cell types originate from a ____
Blood Cell Production:
Hematopoiesis is a continous and highly regulated process of blood cell production that includes cell:
Renewal, proliferation, differentiation, maturation
This process takes place in the bone marrow
All blood cell types originate from a common stem cell production

Explain the 2 WBC stem cell lineages
What are they and what to they become?
Lymphocell line ——–> lymphocytes only
Myeloid progenitor cells —–> Eosinophils, Basophils, Neutrophils, Monocytes

If you see the term ……-blast on the end of a cell type what does that mean?
Lymphoid cell line creates ______ and _____
Megokaryocytes become ________
If you see the term “-blast” it means the cell is still an immature cell, should still be in bone marrow
Lymphoid cell line creates lymphocytes, T cells and B cells
Megokaryocytes become PLATELETS
Blood Cell Maturation:
Differentiation of cell maturity:
Explain what immature cells vs mature cells look like in these various categories:
Cell Size, Cytoplasm Color, Nuclear Content size and color, and nuclear chromatin structure
Differentiation of Cell Maturity (from immature to mature):
- Cell size: from LARGE to small
- Cytoplasm color: from intense BLUE to moderate blue
- Nuclear content size and color: from LARGE to small and from LIGHT to dark
- Nuclear chromatin structure: from light and loose to dark and clumped

Blood Cell Maturation:
Differentiation of cell maturity:
Immature Cells:
- ______ N:C ratio
- _______ are present
Mature Cells:
- ______ N:C ratio
- ______ are defined
- _______ nuclei
Blood Cell Maturation:
Differentiation of cell maturity:
Immature Cells:
- High N:C ratio
- Nucleoli are present
Mature Cells:
- Low N:C ratio
- organelles are defined
- segmented nuclei

Blood Cell Production Stimulation:
______ and other factors stimulate stem cells to produce cell lines via different pathways
Explain what erythropoietin does
GM-CSF stimulates ________ production
Explain what thrombopoietin does
Cytokines and other factors stimulate stem cells to produce cell lines via different pathways
Erhythropoietin, from the kidney, stimulates erythrocyte production via oxygen feedback
GM-CSF stimulates monocyte-macrophage production
Thrombopoietin with other cytokines stimulate megakaryocytes to generate platelets
Explain the function of the following:
Erythropoietin
Thrombopoietin
Erythropoietin, from the kidney, stimulates erythrocyte production via oxygen feedback
Thrombopoietin with other cytokines stimulates megakaryocytes to generate platelets
As blood cells mature, certain morphologic characteristics of maturation allow specific lineages to be recognized:
- _____ in size
- _____ of nucleoli
- _______ of nuclear chromatin
- ________ basophilia (blue color of cytoplasm)
- Organelles become ____
Cytokines and growth factors differentiate stem cells through a multistep process. Cytokines are also necessary to prevent _______
As blood cells mature, certain morphologic characteristics of maturation allow specific lineages to be recognized:
- Decrease in cell size
- Loss of nucleoli
- Condensation of nulear chromatin
- Decreased basophilia (blue color) of cytoplasm
- Organelles become defined
Cytokines and growth factors differentiate stem cells through a multistep process for each cell line.
Megakaryocyte:
- Megakaryocytes are the ______ blood cell in the bone marrow, it is _____nucleated
- _______ are the smalled of the formed elements in blood
- ________, a glycoprotein hormone (produced by the liver and kidney) stimulates the production and differentiation of megakaryocytes
Megakaryocytes:
Megakaryocytes are the largest blood cell in the bone marrow. It is multinucleated
Platelets are the smallest of formed elements in the blood
Thrombopoietin, a glycoprotein hormone (produced by the liver and kidney) stimulates the production and differentiaton of megakaryocytes

Megakaryocytes:
Platelet production: fragments of _____
Platelets are secreted into ____
Do platelets contain a nucleus?
Megakaryocytes:
Platelet production: fragments of the megakaryocyte
Platelets are secreted into the blood ciruclation
Platelets contain NO nucleus in circulation
Clinical hematology Examination of Blood:
What does a CBC look at?
Clinical hematology examination of blood:
A CBC or complete blood cell count:
each cell type is quantified (erythrocytes, leukocytes, platelets)
Hemoglobin and hematocrit are also measured
Red cell parameters are calculated as well

Give the following values:
Normal Levels for Males and Females
Hemoglobin
Hematocrit
Red Cell Count
Normal Levels
Hemoglobin: Males (14-18 g/dL) and Females (12-16 g/dL)
Hematocrit: Males (42-50%) and Females (37-47%)
Red Cell Count: Males (4.6-6 x 106 uL) and Females (4.2-5.4 x 106 uL)

Give the following Normal Values:
Mean Corpuscular Volume (MCV)
Total White Cell Count
Platelets
Mean Corpuscular Volume: 80-100 fL
Total White Cell Count: 4000-11,000/uL (four to eleven thousand per uL)
Platelets: 150k-400k / uL

Give Normal Values for the Following:
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
Remember, total white cell count: 4-11 thousand per uL
Neutrophils: 2500-7500
Lymphocytes: 1500-3500
Monocytes: 200-800
Eosinophils: 60-600
Basophils < 100
This is all PER uL
Remember the plenumonic: nlmeb

Explain what flow cytometry looks at:
It analyzes multiple parameters on _______ from ____ or _____
It looks at ______properties and specific molecules through _______
Discern abnormal populations, cell lineage (leukemia), and clonality
Flow Cytometry:
Analyzes multiple parameters on a large number of cells from blood or bone marrow
It looks at physical properties and specific moleules through monoclonal antibodies
Discern abnormal populations, cell lineage (leukemia), and clonality

Blood Cells Structure and Function:
Erythrocytes (RBCs)
- most ____ cell type in blood
- Carry ____ and _____ to cell and removes ____ such as CO2
Leukocytes (WBCs)
- various cell types
- carry out _____ response, protect the body against infectious disease and foreign invaders
Platelets:
- more numerous than ____ in blood
- Critically important for _____
Blood Cells Structure and Function:
Erythrocytes (RBCs)
- most numerous cell type in the blood
- Carry oxygen and nutrients to cells and removes toxins such as CO2
Leukocytes (WBCs)
- various cell types
- Carry out the immune response; protect the body against infectious disease and foreign invaders
Platelets:
- more numerous than leukocytes in the blood
- Critically important for blood clotting (prevention of blood loss)
Erythrocytes:
________ (shaped) disks
- Increases ____
- Aids in _____ that allows passage through narrow capillaries
Filled with ______ (gives the red color)
_____ are young RBCs that contain some ribosomes and mitochondria
Erythrocytes:
Biconcave shaped discs
- increases Surface Area
- Aids in flexibility that allows passage through narrow capillaries
Filled with hemoglobin (gives the red color)
Reticulocytes are young RBCs that contain some ribosomes and mitochondria
Erythrocytes:
Do RBCs have a nucleus when mature?
RBC average lifespan is approximately _____
Average amount in blood circulation?
Erythrocytes:
RBCs are anuclear when mature
RBC lifespan is 120 days
Average amount in blood circulation is 4 x 106 / uL
Abnormal Red Cell Formation:
What does the terms mean below?
Poikilocytosis
Anisocytosis
Poikilocytosis: Abnormal shape
Anisocytosis: Abnormal volume, diameter

Explain what Hematocrit is
What is the normal hematocrit range?
What are the terms for too high or too low hematocrit
Hematocrit is a measure of how many RBCs are present within the blood
It is given as a percentage (aka what percentage of blood is taken up by RBCs)
Normal Blood: Males (42-52%)
Females (37-47%)
Anemia is low hematocrit, Polycythemia is high hematocrit

Erythrocytes: Hemoglobin
- Hemoglobin is what carries _____
It is a ______ protein composed of __ alpha and __ beta polypeptide subunit
Each alpha and Beta subunit contains a ______ that binds oxygen
There are _____ oxygen binding sites in 1 Hb molecule
Erythrocytes: Hemoglobin
Hemoglobin is what carries oxygen throughout the body
It is a tetrameric protein composed of 2 alpha and 2 beta polypeptide subunits
Each alpha and beta subunit contains a heme-iron complex that binds oxygen
4 oxygen binding sites in 1 Hb molecule

Erythrocytes: Hemoglobin
Heme has ___ at its center
The ___ binds to O2 in the lungs and releases it in the tissues
Hemoglobin:
Heme has iron at its center
The iron binds O2 in the lungs and releases it in the tissues

Leukocytes:
There are 5 different types of leukocytes
What are the types of granulocytes
Monocytes
Lymphocytes
What is the average WBc count in circulating blood
WBCs are the cells of the ______ system
Leukocytes:
There are 5 different types of leukocytes:
- Granulocytes:
- Neutrophils
- Basophils
- Eosinophils
- Monocytes
- Lymphocytes
Average WBC count is 4 x 103 / uL
Leukocytes are the cells of the immune system
Leukocytes: Granulocytes:
- ______ of all the WBCs
- ______ are the most abundant
- _______ and _____ are less abundant
- Nuclei are multi-_____
Cytoplasm contains granules:
Leukocytes:
- Most common of all the WBCs
- Neutrophils are the most abundant
- Eosinophils and basophils are less abundant
- Nuclei are multi-lobed
Cytoplasm contains granules:
- enzymes
- prostaglandins
- Mediators of inflammation
Leukocytes: Granulocytes: Basophils
- Physical appearance?
Function in ________ reactions
Basophils:
Very Dark Blue granules
Function in hypersensitivity reactions
remeber, basophil means blue
when you’re blue you’re hypersensitive

Leukocytes: Granulocytes: Eosinophils:
Physical appearance?
Function in inflammatory response to ____
Involved in _____ reactions
Eosinophils
Large red stained granuels
Function in inflammatory response to parasites
Involved in allergic reactions

Neutrophils:
Comprise the ______ of all cells produced in the bone marrow
Lifespan in blood circulation is about _____
It is the first line of defense against _____
Major function is in ____
Neutrophils:
Comprise the greatest fraction of all cells produced in the bone marrow
Lifespan in blood circulation is about 8 hours
Neutrophils are the first line of defense against bacterial pathogens
Major function is in tissues

Neutrophils:
How do neutrophils function?
What does leukocyte migration mean?
What do granuels contain?
Neutrophils:
Leukocyte migration: neutrophils insert between endothelial cells of a blood vessel wall to reach injury or infection
Granules contain myeloperoxidase that kills bacteria
Neutrophils ingest the ‘dead’ bacteria via phagocytosis

Neutrophils:
Define the term leukopenia
How does leukopenia work with an infection?
Leukopenia: low number of WBCs, results in a higher incidence of bacterial infections
With infection:
Production of neutrophils is upregulated, and blood film will show increased mature neutrophils (neutrophilia)
Increased presence of less mature cells (bands) in circulation (left ward shift)

Fill in the Blank:
A ‘left shift’ is when there is an increased number of ______ in blood circulation
A left shift is when there is an increased bumber of immature leukocytes in blood circulation
happens during leukopenia

Monocytes:
Largest of the WBCs
Lifespan of several months, but only spend ___ in circulation
Reside in tissue where they ________ bacteria
Then ‘present’ component of the bacteria to lymphocytes
Monocytes:
Largest of the WBCs
Lifespan of several months but only spend 3 days in circulation
Reside in tissue where they phagocytize bacteria
Then ‘present’ component of the bacteria to lymphocytes

Lymphocytes:
leave the marrow as precursors and require extramedullary maturation
- _____ and _____ the immune response
- Recognizing ____ vs _____ as vital function
- Increased numbers in circulation with a ____ infection
Lymphocytes:
Leave the marrow as precursors and require extramedullary maturation
- Amplify and refine the immune response
- Recognizing self vs non self is a vital function
- Increased numbers in circulation with a viral infection

Platelets:
Normal Size
Normal Count?
Lifespan in circulation
Daily production of how many?
Platelets:
Normal size: 2-3 um in diameter
Normal Count: 150-450 x 103 /uL
Lifespan in circulation: 7-10 days
Daily production: 1011 platelets
Platelet Structure:
What enables platelet shape change?
What releases substances for platelet function and energy?
What is important for communication w/ the enviornment?
Platelet Structure:
Microtubules and filaments enable platelet shape change
Organelles (dense and alpha) release substances for function and energy
Open canalicular system is important for communication
Also, platelets have a TON OF RECEPTORS

Explain “platelet shape change”
Normally, platelets are in a discoid form
When they are activated they change to spherical shape with extensions in order to increase surface area
This is to facilitate adhesion to a foreign substance

Platelet Structure:
Platelet cytoplasm contains two types of granules that store and secrete coagulation factors and vasoactive molecules
- Alpha/light granules that contain ____ molecules that facilitate platelet ______ (list the molecules)
- Dark granules/dense bodies that contain ____ molecules used by the platelet for ____ (list those molecules)
Platelet Structure:
Platelet cytoplasm contains two types of granules that store and secrete coagulation factors and vasoactive molecules
Alpha/light granuels contain large molecules that facilitate platelet function, and recruit additional platelets to the site of injury (fibrinogen, vWF, FV, FVII, PF4, GF)
Dark granules/dense bodies that contain small molecules used by the platelet for energy: ATP, ADP, serotonin, calcium

The platelet membrane has an array of receptors for adhesion and aggregation and other activation functions
Explain what these key receptors bind to
- Glycoprotein Ia/IIa
- Glycoprotein Ib/IX/X
- Glycoprotein IIb/IIIa
- Glycoprotein Ia/IIa binds to collagen on the endothelial layer of a blood vessel
- Glycoprotein Ib/IX/X binds to VWF
- Glycoprotein IIb/IIIa binds to fibrinogen )on another platelet for aggregation)

What molecule is critical for platelet function?
What are the three major functions of platelets?
Calcium is critical for platelet function
3 Major Function of Platelets:
activation,
adhesion (to a foreign body)
aggregation (with other platelets to form a plug)

Platelets:
_______ is the action of platelets to quickly stop blood loss (body’s first line of defense against bleeding)
Platelets initiate and control ____
Platelets undergo ____ and ____ changes in response to alterations to normal physiology
Platelet functions are integrated with the ____- system of plasma based enzymes
Platelets:
Primary hemostasis is the action of platelets to quickly stop blood loss (body’s first line of defense against bleeding)
Platelets initiate and control hemostasis
Platelets undergo chemical and physical changes in response to alterations to normal physiology
Platelet functions are integrated with the coagulation system of plasma based enzymes
Coagulation System: Secondary Hemostasis
Activation of various coagulation enzymes: convert soluble fibrinogen into insoluble ___
Fibrin forms a ____ ; the fibrin clot provides a ___ that stabilizes the already formed platelet plug
The coagulation cascade is called “secondary hemostasis”
Activation of various coagulation enzyme: convert fibrinogen into soluble fibrin
Fibrin forms a clot: the fibrin clot provides a mesh that stabilizes the already formed platelet plug

Explain the simplified version of the Coagulation cascade

Explain the more fleshed out version of the coagulation cascade
Note, there is a 1000 fold amplification at each step

Which molecule fules the feedback system of the coagulation cascade?
What kind of feed back is it?
THROMBIN feedsback into the coagulation cascade
(positive feedback)
The Coagulation System:
What is the major activator?
What is the primary enzyme?
What are the cofactors?
Which are the inhibitors?
The Coagulation System:
- Major activator is Tissue Factor (TF)
- Primary enzyme is thrombin
Cofactors: Factors V, VIII, Ca2+ and phospholipid
Inhibitors: Antithrombin, TFPI, Protein C, protein S, thromodulin

The coagulation factors are a group of ______ protease enzymes
FV and FVIII serve as _____ to stabilize the protease and increase its activity
_____ and ____ are also cofactors that are required
The coagulation factors are a group of serine protease enzymes
Factor V and VIII act as co-factors to stabilize the protease and increase its activity
Calcium and phospholid are also important cofactors
Most coagulation factors are produced where?
What is the one exception?
What are the factors that are vitamin K dependent?
- they require an addition of a carboxylase group to create a pocket for _____ binding
- this step requires a gamma carboxylase which needs vitamin K for activation
Most of the coagulation factors are produced in the liver, exept factor FVIII is produced in endothelial cells
Vitamin K Dependent: FII (prothrombin), FV, FIX, FX
They require an addition of a carboxylase group to create a pocket for Ca++ binding
________ is the ultimate substrate of the coagulation pathway
_______ is converted to its insoluble form _____ by _____ cleavage
____ is the primary structural protein of the blood clot
Fibrinogen is the ultimate substrate of the coagulation pathway
Fibrinogen is converted to its insoluble form fibrin by thrombin cleavage
Fibrin is the primary structural protein of the blood clot

The final fibrin clot is stabilized by ______
The final fibrin clot is stabilized by Factor XIII
The main enzyme in the fibrinolytic system is _____
The main activators are ____ and _____
_____ converts plasminogen into its more active form ____
_____ then digests its substrates fibrin, fibrinogen, FV, and FVIII
Main enzyme in fibrinolytic system is plasminogen
The main activators are TPA and UPA
TPA converts plasminogen into its more active form plasmin
Plasmin then digests its substrates fibrin, fibrinogen and FV, and FVIII
Fibrin Degradation:
The degradation products are _______ structurally specific to the fibrin molecule
The presence of ______ is a specific indicator that fibrin formation and blood clotting has occured
Fibrin Degradation:
The degradation products are D dimers, strucutrally specific to the fibrin molecule
The presence of D dimers is a specific indicator that fibrin formation and blood clotting has occured