CH 18. - Blood

Hematology

the study of blood

What were once thought to be transmitted through blood?

Hereditary traits

What type of cells were seen with the first ever microscopes?

Blood cells

4 Humors:

1. blood

2. bile

3. saliva

4. urine

Circulatory System consists of…

consists of the heart, blood vessels, and blood

Cardiovascular System refers only to the. . .

heart and blood vessels

Functions of the Circulatory System:

1. Transport

   • transporting things like O2, CO2, nutrients, wastes, hormones, etc

2. Protection

   • inflammation, limits spread of infection, destroys microorganisms and cancer cells, neutralizes toxins, and initiates clotting

3. Regulation

   • maintains homeostasis through fluid balance, stabilizing pH of ECF, and temp control

Components/Properties of Blood

Blood is a liquid connective tissue made of cells and an extracellular matrix

Includes:

• Plasma

• Formed Elements

*Adults have 4-6 liters of blood

• smaller people have less blood, larger people have more blood

Plasma

the matrix/liquid of blood

• Clear, light yellow fluid

• has very little protein

Formed Elements

blood cells and cell fragments

• includes red blood cells, white blood cells, and platelets

7 Kinds of Formed Elements:

1. Erythrocytes - RBCs

2. Thrombocytes - platelets

3. Neutrophils

4. Eosinophils

5. Basophils

6. Lymphocytes

7. Monocytes

Platelets

Cell fragments from a special cell in bone marrow

Leukocytes

white blood cells

5 leukocyte types divided into 2 categories:

• Granulocytes

• Agranulocytes

Granulocytes

WBCs with granules

Includes:

• Neutrophils

• Eosinophils

• Basophils

Agranulocytes

WBCs without granules

Includes:

• Lymphocytes

• Monocytes

Order of WBCs from most common to least common/abundant:

Never Let Monkeys Eat Bananas

1. Neutrophils

2. Lymphocytes

3. Monocytes

4. Eosinophils

5. Basophils

Hematocrit

measures the ratio of plasma to formed elements

• centrifuges blood to separate components

• Erythrocytes are heaviest and settle first

  • make up 37% to 52% total volume

• White blood cells and platelets make up the middle layer

  • 1% total volume

  • has a buffy coat

• Plasma

  • makes up remainder of volume

    • 47% to 63%

  • Complex mixture of water, proteins, nutrients, electrolytes, nitrogenous wastes, hormones, and gases

Serum in Plasma:

the remaining fluid when blood clots and solids are removed

• Identical to plasma except for the absence of fibrinogen

3 major categories of plasma proteins:

1. Albumins

2. Globulins

3. Fibrinogen

Plasma proteins are formed by the liver

• Except globulins which are produced by plasma cells

Albumin

• smallest and most abundant plasma protein

• Contributes to viscosity and osmolarity

• influences blood pressure, flow, and fluid balance

Globulin

AKA antibodies

• Responsible for the immune response

• Made of alpha, beta, and gamma globulins, which combine to make hemoglobin

• these do not directly target bacteria, they highlight the bacterial cells so white blood cells know what to destroy

• produced by plasma cells

Fibrinogen

Blood clotting protein

• is a precursor protein (almost active protein)

• is one covalent bond from becoming fibrin, which is what we actually use for blood clotting

• can be dissolved in water, while fibrin cannot

Other Components of Blood Plasma:

1. Nitrogenous Compounds

2. Nutrients

3. Gases

4. Electrolytes

Nitrogenous Compounds in Plasma

Includes:

• Free amino acids from dietary protein or tissue breakdown

• Nitrogenous wastes (urea)

  • toxic end products of catabolism

  • usually removed by kidneys and excreted through urine

Nutrients in Plasma

Anything that can be metabolically active

Includes:

• Glucose

• Vitamins

• Fats

• Cholesterol

• Phospholipids

• Minerals

*You need a little bit of these, but not too much

Gases in Plasma

Dissolved O2, CO2, and nitrogen

• CO2 is essential for maintaining blood homeostasis, it is not always a waste product

Electrolytes in Plasma

Sodium (Na+) makes up majority (90%) of cations in plasma

Viscosity

how thick a fluid is / the rate of flow of a fluid

• Whole blood is 4.5 to 5.5 times as viscous as water

• Plasma is 2x as viscous as water

  • Important in circulatory function

• Erythrocytes have the highest influence on blood viscosity

Osmolarity of Blood

the total molarity of the dissolved particles that cannot pass through the blood vessel wall

• osmolarity pulls fluid across membrane

• If too high, blood absorbs too much water, increasing the blood pressure

• If too low, too much water stays in tissue, blood pressure drops, and edema (swelling) occurs

  • hard time retaining fluids

• Optimum osmolarity is achieved by the body’s regulation of sodium ions, proteins, and red blood cells

Hemopoiesis

production of blood (especially its formed elements)

How Blood is Produced (5 ways):

• Hemopoietic Tissues

• Multipotent Stem Cells (hemocytoblasts)

• Colony-Forming Unit

• Myeloid Hemopoiesis

• Lymphoid Hemopoiesis

How Hemopoietic Tissues Produce Blood

Hemopoietic tissues produce blood cells at a very high rate

• Yolk sac stem cells create the first blood cells in utero

• these colonize in fetal bone marrow, liver, spleen, and thymus

  • Liver stops producing blood cells at birth

• Spleen remains involved with lymphocyte production and stores red blood cells

What is the primary site for hemopoiesis in adults?

red bone marrow

Hemocytoblasts / Hemopoietic Stem Cells

Red blood cell builders

• type of multipotent stem cell

Colony-Forming Unit

specialized stem cells that only produce one class of formed element of blood

• divides over and over again to form one kind of blood

Myeloid Hemopoiesis

blood formation in the bone marrow

Lymphoid Hemopoiesis

blood formation in the lymphatic organs

• beyond infancy, this only involves lymphocytes

2 Principal Functions of Erythrocytes:

Gas transport = major function

1. Carry oxygen from lungs to cell tissues

2. Pick up CO2 from tissues, modify it to not carbonate the blood, and bring it to the lungs

   • does NOT transport CO2

Structure of Erythrocytes

• a disc-shaped cell with a thick rim

• loses nearly all of its organelles during development so the cell wont consume O2 and can transport it instead

  • lacks mitocondria

    • uses anerobic fermentation to produce ATP

  • lack of nucleus and DNA

    • NO protein synthesis or mitosis

• concave shape maximizes surface area, which allows for faster rate of diffusion

What is blood type determined by?

surface glycoproteins and glycolipids

Cytoskeleton of Erythrocytes:

spectrin and actin

• give the membrane durability and resilience

• They stretch and bend as they are squeezed through small capillaries

What is the most common dissolved substance in erythrocytes?

Hemoglobin

• 33% of the cytoplasm in RBCs is hemoglobin

• helps deliver O2 to tissues and CO2 to the lungs

Carbonic Anhydrase (CAH) in the Cytoplasm

CAH is the enzyme that turns CO2 into carbonic acid

• important role in blood pH balance and gas transport

• keeps our blood from becoming carbonated

Each hemoglobin (Hb) molecule contains:

• 4 protein chains (globins)

  • adult Hb has 2 alpha and 2 beta chains

  • fetal Hb has 2 alpha and 2 gamma chains bc gamma has a higher affinity for O2

  • globins bind to CO2

• 4 heme groups

Heme Groups

a nonprotein component that binds O2 to Fe at its center

• 4 heme groups = 4 iron molecules in hemoglobin

What is the ratio of globular protein to heme to stored oxygen?

1 globular protein - 1 heme - 1 stored oxygen

What determines that amount of O2 blood can carry?

RBC count and hemoglobin concentration

RBC Hematocrit Men vs. Women:

the percentage of the whole blood volume that is composed of red blood cells

• Men have higher RBC hematocrit, related to testosterone (high skeletal muscle, low adipose) compared to women

• Men typically have higher hemoglobin concentration and RBC count

• too high of a hematocrit causes mini clots and mini heart attacks

Values are lower in women because…

• Androgens stimulate RBC production, which women have less of

• Women have periodic menstrual losses

• Hematocrit is inversely proportional to percentage of body fat, which women have more of

  • Increased androgens correlate to lower body fat percentage

Erythropoiesis

red blood cell production

• 1 million RBCs are produced per second

• we replace our RBCs approx. 3 times a year

• development takes 3-5 days

  • Reduction in cell size, increase in cell number, synthesis of hemoglobin, and loss of nucleus

• the first cell is a colony-forming unit that has receptors for erythropoietin (EPO) from the kidneys

  • erythropoietin triggers erythropoiesis in the body

Iron (Fe)

a key nutritional requirement

• dissolved iron is very metabolically active

• it is lost daily through urine, feces, and bleeding

  • Men 0.9 mg/day and women 1.7 mg/day

• Low absorption rate of iron requires consumption of 5 to 20 mg/day

• to minimize bacteria growing in the blood stream, we have a protein called liver apoferritin that binds to iron to make ferritin so bacteria have a hard time accessing the iron

Steps of Iron Metabolism

1. We ingest iron through our diet

2. stomach acid converts Fe3+ to Fe2+

3. Fe2+ binds to gastroferritin

4. Gastroferritin carries iron to small intestine where it releases the iron

5. iron will be absorbed into blood stream by binding to transferrin

6. goes to the liver for storage

7. can be further processed in the liver

Negative Feedback Loop for Erythrocytes

• a drop happens in RBC count, causing hypoxemia (low O2) to be detected by the kidneys

• the kidney then produces erythropoietin which stimulates bone marrow

• RBC count then increases in 3-4 days

What stimulates an increase in erythropoiesis?

• low levels of O2

• high altitude

• increase in exercise

• loss of lung tissue in emphysema

Where do Erythrocytes rupture?

RBCs rupture (hemolysis) in narrow channels of spleen and liver

9 Steps of Erythrocyte Death and Disposal

1. macrophages in spleen digest ruptured RBC membrane bits and separate the heme from the globin

2. in the small intestine, we ingest and absorb iron and other raw building blocks for erythrocytes

3. these materials enter the blood stream and go into red bone marrow

4. Then, we form erythrocytes, which circulate for 4 months before they die

5. dead ones are filtered out of the blood in the spleen

6. nutrients go back into the bloodstream, but the heme from the iron needs to get processed

7. iron is stored in liver to be reused while the rest of the heme group gets processed into biliverdin (one of the key components of bile)

8. Biliverdin gets converted to bilirubin and is released into bloodstream and filtered through the kidneys

9. some bilirubin will go into the digestive system, where it gets converted to urobilinogen (makes feces brown)

What makes our feces brown?

urobilinogen

Polycythemia

an excess of RBCs

• 2 types: Primary polycythemia and Secondary polycythemia

Primary Polycythemia

aka polycythemia vera

• Cancer (out of control production) of the erythropoietic cell line in red bone marrow

  • diagnosed when individual has a hematocrit of 80% RBC count (RBC count up to 8 million RBCs/μL)

Secondary Polycythemia

excessive RBC production caused by dehydration, emphysema, high altitude, or physical conditioning

• RBC count up to 8 million RBCs/μL

• hard time getting oxygen into blood - emphysema

What is the most common cause of polycythemia?

out of control hemocytoblasts in red bone marrow

Dangers of Polycythemia

• Increased blood volume, pressure, viscosity

  • makes blood more likely to clot

• Can lead to embolism, stroke, or heart failure

3 Causes of Anemia:

1. Inadequate erythropoiesis or hemoglobin synthesis

2. Hemorrhagic anemia from bleeding

3. Hemolytic anemia from destruction of RBC

5 ways inadequate erythropoiesis can happen:

• kidney failure and insufficient erythropoietin

• Iron-deficiency anemia

• Pernicious anemia

• Hypoplastic anemia

• Aplastic anemia

Pernicious Anemia

autoimmune attack of stomach tissue that leads to inadequate Vitamin B12 absorption

Hypoplastic Anemia

slowing of erythropoiesis

Aplastic Anemia

complete cessation of erythropoiesis

What is the most common source of anemia?

Inadequate erythropoiesis

What type of anemia has RBCs that appear hollow or empty?

iron-deficiency anemia

• can make erythrocytes, but have a hard time filling them

3 potential consequences of anemia:

• Tissue hypoxia (low O2) and necrosis

  • Patient is lethargic

  • Shortness of breath upon exertion

  • Life-threatening necrosis of brain, heart, or kidney

• Blood osmolarity is reduced, producing tissue edema (excess fluid/swelling)

• Blood viscosity is low

  • Heart races and pressure drops

  • Cardiac failure may happen

Blood types and transfusion compatibility are determined by. . .

interactions between plasma proteins and erythrocytes

Blood types are based on interactions between . . .

antigens and antibodies

Antigens

Complex molecules on the surface of the cell membrane that activate an immune response

• We have 3 medically important antigens

  • we have over 200, but only 3 are medically important

• They are genetically unique to the individual

• Used to distinguish self from foreign matter

• Foreign antigens generate an immune response

Agglutinogens

antigens on the surface of the RBC that are the basis for blood typing

Antibodies

Proteins (gamma globulins) secreted by plasma cells

• Part of immune response to foreign matter

• You DO NOT form antibodies against your antigens

• Bind to antigens and mark them for destruction

• Forms antigen–antibody complexes

• antibodies do not directly destroy the invader, but will highlight the issue and recruit leukocytes

the immune system should be trained not to be activated by. . .

self-antigens

Agglutinins (antibodies)

antibodies in the plasma that bring about transfusion mismatch

• Found in plasma

• Anti-A, anti-B, & anti-Rh

Clumping (Agglutination)

Process of an antibody molecule binding to antigens

• Erythrocytes are stuck together by antibodies

• Causes clumping of red blood cells

• we don’t clot our blood, we clump our blood

Red Blood Cell Antigens

• antigen A

• antigen B

• antigen Rh(D)

Determined by glycolipids on RBC surface

How is your ABO bloody type determined?

by the presence or absence of antigens on RBCs

Blood type A person has …

Blood type B person has …

Blood type AB has …

Blood type O person has …

• Blood type A person has A antigens

• Blood type B person has B antigens

• Blood type AB has both A and B antigens

• Blood type O person has neither antigen

What are the most common and most rarest blood types?

Most common: type O

Rarest: type AB

______ blood types has Rh antigen, ______ lack Rh antigen.

Positive blood types has Rh antigen, negative lack Rh antigen

How to test blood type:

• use Antibodies anti-A and anti-B and mix with samples of the blood

• You DO NOT form antibodies against your antigens, so your blood will mix with the antibodies and clot if your RBCs have the antigen

Why do we only want to introduce blood that has self-antigens to a patient?

Because otherwise clumping can happen

• Each antibody can attach to several foreign antigens on several different RBCs at the same time

• Responsible for mismatched transfusion reaction

• Agglutinated RBCs block small blood vessels, hemolyze, and release their hemoglobin over the next few hours or days

• Hb blocks kidney tubules and causes acute renal failure

Universal Donor

• Type O-

• No RBC antigens

• Donor’s plasma may have both antibodies against recipient’s RBCs (anti-A, anti-B, anti-Rh)

• May give packed cells (minimal plasma)

  • we separate blood plasma and blood cells to separate antibodies

Universal Recipient

• Type AB+

• Lacks plasma antibodies

  • no anti-A, anti-B, or anti-Rh

If you have A blood type, you will be making ______ anitbodies.

If you have B blood type, you will be making ______ antibodies.

It you have O blood type, you will be making ______ antibodies.

If you have A blood type, you will be making anti-B anitbodies.

If you have B blood type, you will be making anti-A antibodies.

If you have O blood type, you will be making both anti-A and anti-B antibodies.

If you have negative blood type…

you cannot receive positive blood types

If you have positive blood type…

You can receive both positive and negative blood types

Hemolytic Disease of the Newborn

after a - blood type mother gives birth to a + blood type baby, the moms anti-rH antibodies will cross over and attack the babies blood

• will only happen if mom has negative blood type

• can tell if there is hemolytic disease if there is nucleated erythrocytes in the blood stream

• Second pregnancy mother with negative blood type is most likely to develop this disease

How can we help Hemolytic Disease?

We inject the mom (who has - blood type) with anti-rH antibodies bc they will bind to the fetal rH-postive cells and "mask" them, making them invisible to the mother's immune system and stopping the immune response that would otherwise destroy the baby's red blood cells

• If both parents are negative, you dont need to inject anti-rH antibodies bc its impossible to get a + blood baby then

Leukocyte Characteristics

• least abundant formed element

  • 5,000 to 10,000 WBCs/μL

  • if more than that, your body is actively fighting off an infection

• huge nucleus

  • needs one bc it makes a lot of proteins to fight off invaders

• Spend only a few hours in the bloodstream before moving to connective tissue

• Keep their organelles for protein synthesis

• Have granules (membrane-bound organelles)

Granules in Leukocytes

• All WBCs (leukocytes) have lysosomes called nonspecific granules

• Granulocytes (a type of WBC) have specific granules that have enzymes and other chemicals employed in defense against pathogens

Types of Leukocytes:

Granulocytes and Agranulocytes

Granulocytes include:

• Neutrophils

• Eosinophils

• Basophils

Agranulocytes include:

• Lymphocytes

• Monocytes

Neutrophils

fight off bacteria

• makes up 60% to 70% of leukocytes

• have multi lobe nuclei

• the most common leukocyte

• Have barely visible granules in the cytoplasm

• 1.5x diameter of a erythrocyte

Eosinophils

fight off parasitic infections

• make up 2% to 4% of leukocytes

• Have large rosy-orange granules

• has a bilobed nucleus

• Phagocytize (eating) antigen–antibody complexes, allergens, and inflammatory chemicals

• Release enzymes to destroy large parasites

• 4th most common leukocyte

Basophils

involved with allergies

• have purple granules fill cytoplasm

• secretes histamine

  • this causes blood vessels to expand and let more blood flow to an area, causing area to be warm and red (inflammation)

• secretes heparin -

  • this regulates blood clotting so its easier to get white blood cells to infection

  • you want a happy medium of it

Lymphocytes

Destroys human cells (cancer, foreign, and virally infected cells)

• most complicated

• part of our active immune system

  • make our T cells and B Cells

• “Present” antigens to activate other immune cells

• Coordinate actions of other immune cells

• Secrete antibodies and provide immune memory

• look for little sliver of cytoplasm to tell the difference between these and basophils

Monocytes

• increased number of them in viral infections and inflammation

• Very large, 2-3x the diameter of erythrocytes

• have a horseshoe or C-shaped nucleus

• Leave bloodstream and transform into macrophages

  • these go around swallowing things that do not belong there

  • will only swallow if its been covered in antibodies

  • “Present” antigens to activate other immune cells—antigen-presenting cells (APCs)