Exam 2: Walenga 1

Question 1

Blood:

A complex fluid composed of ____& ______

Blood is considered a _______

Humans posses roughly ___ of blood in total

Answer 1

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

Question 2

Explain the three different cell types in blood:

What are they called?

Normal number for each?

What is their function?

Answer 2

1. Erythrocytes (RBCs)

• most abundant, 5 x 10⁶ / uL
• carry O2 via hemoglobin

2. Leukocytes (WBCs)

• 5 x 10³ / uL
• mediate immune response to infection and stimulate inflammation
• engulf foreing particles, antibody production

3. Platelets or “thrombocytes”

• 250 x 10³ / uL
• important in blood coagulation

Question 3

Explain all of the components of plasma (hint there are three)

Answer 3

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

Question 4

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 ____

Answer 4

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

Question 5

Explain the 2 WBC stem cell lineages

What are they and what to they become?

Answer 5

Lymphocell line ——–> lymphocytes only

Myeloid progenitor cells —–> Eosinophils, Basophils, Neutrophils, Monocytes

Question 6

If you see the term ……-blast on the end of a cell type what does that mean?

Lymphoid cell line creates ______ and _____

Megokaryocytes become ________

Answer 6

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

Question 7

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

Answer 7

Differentiation of Cell Maturity (from immature to mature):

1. Cell size: from LARGE to small
2. Cytoplasm color: from intense BLUE to moderate blue
3. Nuclear content size and color: from LARGE to small and from LIGHT to dark
4. Nuclear chromatin structure: from light and loose to dark and clumped

Question 8

Blood Cell Maturation:

Differentiation of cell maturity:

Immature Cells:

• ______ N:C ratio
• _______ are present

Mature Cells:

• ______ N:C ratio
• ______ are defined
  
  • _______ nuclei

Answer 8

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

Question 9

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

Answer 9

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

Question 10

Explain the function of the following:

Erythropoietin

Thrombopoietin

Answer 10

Erythropoietin, from the kidney, stimulates erythrocyte production via oxygen feedback

Thrombopoietin with other cytokines stimulates megakaryocytes to generate platelets

Question 11

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 _______

Answer 11

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.

Question 12

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

Answer 12

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

Question 13

Megakaryocytes:

Platelet production: fragments of _____

Platelets are secreted into ____

Do platelets contain a nucleus?

Answer 13

Megakaryocytes:

Platelet production: fragments of the megakaryocyte

Platelets are secreted into the blood ciruclation

Platelets contain NO nucleus in circulation

Question 14

Clinical hematology Examination of Blood:

What does a CBC look at?

Answer 14

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

Question 15

Give the following values:
Normal Levels for Males and Females

Hemoglobin

Hematocrit

Red Cell Count

Answer 15

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)

Question 16

Give the following Normal Values:

Mean Corpuscular Volume (MCV)

Total White Cell Count

Platelets

Answer 16

Mean Corpuscular Volume: 80-100 fL

Total White Cell Count: 4000-11,000/uL (four to eleven thousand per uL)

Platelets: 150k-400k / uL

Question 17

Give Normal Values for the Following:

Neutrophils

Lymphocytes

Monocytes

Eosinophils

Basophils

Answer 17

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

Question 18

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

Answer 18

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

Question 19

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 _____

Answer 19

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)

Question 20

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

Answer 20

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

Question 21

Erythrocytes:

Do RBCs have a nucleus when mature?

RBC average lifespan is approximately _____

Average amount in blood circulation?

Answer 21

Erythrocytes:
RBCs are anuclear when mature

RBC lifespan is 120 days

Average amount in blood circulation is 4 x 10⁶ / uL

Question 22

Abnormal Red Cell Formation:

What does the terms mean below?

Poikilocytosis

Anisocytosis

Answer 22

Poikilocytosis: Abnormal shape

Anisocytosis: Abnormal volume, diameter

Question 23

Explain what Hematocrit is

What is the normal hematocrit range?

What are the terms for too high or too low hematocrit

Answer 23

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

Question 24

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

Answer 24

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

Question 25

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

Answer 25

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

Question 26

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

Answer 26

Leukocytes: There are 5 different types of leukocytes: - Granulocytes: * 1. Neutrophils * 2. Basophils * 3. Eosinophils 4. Monocytes 5. Lymphocytes Average WBC count is 4 x 10³ / uL Leukocytes are the cells of the immune system

Question 27

Leukocytes: Granulocytes: - ______ of all the WBCs - ______ are the most abundant - _______ and _____ are less abundant - Nuclei are multi-\_\_\_\_\_ Cytoplasm contains granules: * * *

Answer 27

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

Question 28

Leukocytes: Granulocytes: **Basophils** - Physical appearance? Function in ________ reactions

Answer 28

Basophils: Very Dark Blue granules Function in **hypersensitivity reactions** remeber, basophil means blue when you're blue you're hypersensitive

Question 29

Leukocytes: Granulocytes: Eosinophils: Physical appearance? Function in inflammatory response to \_\_\_\_ Involved in _____ reactions

Answer 29

Eosinophils Large red stained granuels Function in inflammatory **response to parasites** Involved in **allergic reactions**

Question 30

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 \_\_\_\_

Answer 30

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

Question 31

Neutrophils: How do neutrophils function? What does leukocyte migration mean? What do granuels contain?

Answer 31

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**

Question 32

Neutrophils: Define the term leukopenia How does leukopenia work with an infection?

Answer 32

**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**)

Question 33

# Fill in the Blank: A 'left shift' is when there is an increased number of ______ in blood circulation

Answer 33

A left shift is when there is an increased bumber of immature leukocytes in blood circulation happens during leukopenia

Question 34

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

Answer 34

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

Question 35

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

Answer 35

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**

Question 36

Platelets: Normal Size Normal Count? Lifespan in circulation Daily production of how many?

Answer 36

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

Question 37

Platelet Structure: What enables platelet shape change? What releases substances for platelet function and energy? What is important for communication w/ the enviornment?

Answer 37

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

Question 38

Explain "platelet shape change"

Answer 38

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

Question 39

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)

Answer 39

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

Question 40

The platelet membrane has an array of receptors for adhesion and aggregation and other activation functions Explain what these key receptors bind to 1. Glycoprotein Ia/IIa 2. Glycoprotein Ib/IX/X 3. Glycoprotein IIb/IIIa

Answer 40

1. Glycoprotein Ia/IIa binds to collagen on the endothelial layer of a blood vessel 2. Glycoprotein Ib/IX/X binds to VWF 3. Glycoprotein IIb/IIIa binds to fibrinogen )on another platelet for aggregation)

Question 41

What molecule is critical for platelet function? What are the three major functions of platelets?

Answer 41

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)

Question 42

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

Answer 42

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

Question 43

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

Answer 43

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

Question 44

Explain the simplified version of the Coagulation cascade

Answer 44

Question 45

Explain the more fleshed out version of the coagulation cascade

Answer 45

Note, there is a 1000 fold amplification at each step

Question 46

Which molecule fules the feedback system of the coagulation cascade? What kind of feed back is it?

Answer 46

THROMBIN feedsback into the coagulation cascade (positive feedback)

Question 47

The Coagulation System: What is the major activator? What is the primary enzyme? What are the cofactors? Which are the inhibitors?

Answer 47

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

Question 48

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

Answer 48

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

Question 49

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

Answer 49

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

Question 50

\_\_\_\_\_\_\_\_ 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

Answer 50

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

Question 51

The final fibrin clot is stabilized by \_\_\_\_\_\_

Answer 51

The final fibrin clot is stabilized by Factor XIII

Question 52

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

Answer 52

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

Question 53

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

Answer 53

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