Blood

Dr. Robert AndersonRowan University

Components of Blood• Functions

• Distribution of materials to the tissues in the body• _________________• _________________• __________________• __________________

• Regulation• ___________________• ___________________• ___________________• __________________________

• Protection• ______________• __________________

Blood Components• Plasma – liquid component of blood (55% of

blood volume)• ______________• ______________• ______________• ______________• Proteins and amino acids

• Formed elements (cells)• _______________ – White blood cells (~1% of

blood volume)• _______________ – Red blood cells (~44% of

blood volume)• ___________ – help in forming clots

water

sugar

saltshormones

Leukocytes

Erythrocytes

Thrombocytes

Plasma• 90% water

• Solutes• Proteins – transport proteins (chaperones)• Enzymes• Antibodies• Fibrinogen (forms fibrin to clot blood after

injury)

• The proper chemical balance of plasma is essential for tissue function!• Examples?

Metabolites in Plasma

• Cellular Metabolites (Nitrogen containing compounds)• Urea, uric acid, creatine, ammonia (NH3)

• Electrolytes• _________ – Na+, K+, Mg+, Ca+

• __________ – Cl-, PO4-, SO4

-, CO3-

•Respiratory Gases• _____,_______

CationsAnions

O2 CO2

Formed Elements

• Erythrocytes – Red Blood Cells (RBC’s)

• ____________ cells• NO Nucleus!• Mostly composed of _____________ molecules• They do NOT use O2 for respiration (use

_________________________ instead)

• Why are all of these things adaptive??

Lactic Acid Fermentation

Hemoglobin

Biconcave

Hemoglobin

• Quaternary protein molecule made of two functional parts

• _________ – proteins wound together (4 total) to hold heme molecule

• _________ – molecule that hold Iron atoms (Fe) which have a high affinity for O2

• How does this relate to the Central Dogma of Biology?

Two

Heme

Sickle Cell Anemia

• In ______________________, globin proteins are not formed correctly, making O2 transport difficult

• Low O2 content changes the cell to be sickle-shaped (no longer biconcave)

• This causes “traffic jams” in the bloodstream, leading to clots

Sickle Cell anemia

How can Sickle Cell be Beneficial?• Mendelian pattern of inheritance (SSA is recessive)

• BB – no allele for SSA• Bb – carrier for SSA (mildly expressed)• bb – two alleles for SSA (full phenotype)

B bBb

B BBb

B Bbb

Malaria• Mosquito-borne parasite that enters

and develops in red blood cells• Over 500 million malaria infections

annually with ~ 5 million deaths

• Malaria trophozoites (feeding stage) develop in red blood cells• Cause lysis when emerging from cell

• Cell “sickling” makes blood cells more resistant to parasite attack!

Anopheles mosquito (vector for Malaria)

Diseases Change our Gene Pool!

Prevalence Map – Sickle Cell Anemia

Prevalence Map – Malaria

Anemia• A decrease in _____________________________________________• Leads to general fatigue and malaise• Increased cardiac output

• What factors can cause anemia?

1. __________________

2. _________________________

3. _____________/____________

Blood hemoglobin

Poor diet

Globin mutation (ineffective protein)

Injury hemorrhage

Leukocytes

• Specifically engage different invaders of the body (pathogen types)• Divided into granulocytes and agranulocytes due to

their appearance under the microscope • _______________ – many stained organelles giving them a

“grainy” appearance• _______________ – few or no organelles

granulocytes

agranulocytes

Specific Jobs of Leukocytes - Granulocytes

• ____________ – produce histamine leading to inflammatory response• Rarest population

• _____________ – phagocytose bacteria and viruses• 3-6 nuclear lobes

• _____________ – lead attack against parasitic worms• Bilobed nucleus• Also phagocytose bacteria

Basophils

Neutrophils

Eosinophils

Specific Jobs of Leukocytes - Lymphocytes

• Lymphocytes – produce antibodies against specific invaders• B lymphocytes – produce antibodies to pathogens• T lymphocytes

• produce cytokines that direct immune response (CD4 cells)

• Destroy infected cells (CD8 cells)

• These cells are the heart of adaptive immunity, as they and their clones will “remember” the antibodies they produced

Specific Jobs of Leukocytes - Monocytes

• Monocytes – function to ___________ bacteria and other invading pathogens

• Will mature into macrophages which can leave the blood vessels and enter tissues where pathogens frequently enter (_____________)

phagocytize

diapedesis

Phagocytosis

•WBC’s (Macrophages, eosinophils and neutrophils) surround and engulf pathogens

•WBC then adheres to the pathogen via binding of cell membrane components

• This process can be facilitated by opsonization- antibodies or other proteins (complement) mark the pathogen for death by sticking to it

Opsonization

WBC

Germ

Antibodies and protein “markers” from host

• Once adherence is complete, pathogens are engulfed via endocytosis, which forms a phagosome

• The contents of the phagosome are then digested by merging with a lysosome (vesicle in the cell containing digestive enzymes)

Phagocytosis

Phagocytosis

Differential Hemocyte Count

• Depending on the pathogen, infection will cause changes in the proportion of WBC’s in the blood

Neutrophils

Eosinophils

Basophils

Lymphocyt

es

Monocytes

0

1000

2000

3000

4000

5000

6000

7000

8000

Differential WBC Count

NormalInfectedCe

lls/u

l

What type of infection does this person have?

1/7 of the Human population suffers from worm infections – WHY?

Origins - Erythropoiesis

•Blood cells are made from stem cells (Hemocytoblasts) in the bone marrow and differentiate into:

• Erythrocytes• Leukocytes•Platelets

All red blood cells develop from undifferentiated stem cells in the red bone marrow

(Notice the ejection of the nucleus)

White Blood cells also develop from undifferentiated stem cells in the red bone marrow

Platelets

• Essential for blood clotting

• Form from a megakaryocyte that breaks off bits of its cytoplasm and membrane

•Cytoplasmic “chunks” enter blood stream and form platelets

Blood Typing

Erythrocytes• Antigens (Agglutinogens) – surface glycoproteins that

are inherently different between blood types (4 types)

“A” Antigen

“B” Antigen

Type A Type B

Type AB Type O

Antibodies• Proteins that are created by the immune system to

recognize “__________” organisms/chemicals• Antigens on bacteria, fungi, protozoans, other pathogens

or other molecules

• People with different blood types can develop antibodies that will attack “non-self” antigens erythrocytes

Blood Types and Antibodies

Type B

Type A

Type AB

Antigens Antibodies

Type O

Blood Type

Type A

Type B

Type O

Type AB

Y_________

__________

Y________AND __________

_________

Y

YWhat happens if blood types are mixed in a transfusion?

Antigen + Complementary Antibody

Type A erythrocyte

“Anti – A” antibody =

This results in “agglutination”, or the sticking together of hemocytes to their complement antibodies, causing blood cells to

stick together and clump

Y YY

• In addition to the glycoproteins that equate to blood type (A,B) the “Rh” glycoprotein can be either present or absent• People that are “Rh negative” can have the antibodies

to the Rh antigen

• This is what is represented by the + or – in blood types; (e.g. O+ = O blood type with RH factor (antigen), and therefore no antibodies to Rh)

Rh Factor

Rh Factor and Adaptive Immunity• The immune system has a memory, after exposure to

an antigen, your body will “remember” what antibodies to make to attack that antigen

• This becomes a problem in women that are Rh-negative, and are pregnant with an Rh positive baby

• Why?

• After a first pregnancy, blood from the baby can “mix” with blood from the mother during labor, C-section, even abortion

• If the baby is Rh+ and the mother Rh-, the mother’s body will produce antibodies to Rh

• Future pregnancies could be at risk, therefore, immune modulators must be administered (RhoGam)

Rh Factor and Adaptive Immunity

Blood Typing Practice

• Go here to get practice performing transfusions in the context of blood type

• Be sure to ask yourself WHY the outcomes happen in the different scenarios

• http://www.nobelprize.org/educational/medicine/bloodtypinggame/game/index.html

Clotting (Hemostasis)

• A coordinated series of events to stop the flow (loss) of blood

1. Vascular spasm2. Platelet plug formation3. Coagulation

Vascular Spasm• Upon damage, the vessel responsible for

the loss of blood will constrict (vasoconstriction)

• This is due to: • Damage to smooth muscle lining the vessel• Pain receptor stimulation• Chemicals released by platelets and epithelial

cells lining the vessel

Platelet Plug Formation

• Platelets will clump together due to several clotting factors

• Platelets stick tenaciously to the ___________ exposed in damaged blood vessels• A large protein (__________________) links platelets at the plug to each other

and to the collagen in the vessel wall• ADP and serotonin released from platelets also increase the platelet aggregation

to form a clot

Coagulation

• The release of clotting factors changes prothrombin (a plasma protein) into thrombin (an enzyme)

• Thrombin catalyzes fibrinogen (also present in plasma) into fibrin – a molecular polymer that creates a mesh to trap RBC’s and platelets

Fibrin mesh Red Blood Cell

Clot Retraction• Platelets contain actin and myosin that will

contract the clot (increases in density)

• Platelet derived growth factor (PDGF)• Stimulates the growth of

________________and _________________that repair the damaged vessel

• An activated enzyme (______________) eventually breaks down the fibrin after being activated by factors derived from endothelial cells surrounding the clot

Normal Clot Retraction

Abnormal Clot Retraction

Clotting Issues• Embolism – clot breaks from vessel wall

and moves through the blood vessels

• How can this be a problem?

• Clots can be broken up via anticoagulants (aspirin, warfarin, heparin) which inhibits clotting factors

Bleeding Disorders

• _________________ – low platelet count • How can this happen?

• Hemophilia – genetic disorder (Mendelian) that results in low/no production of clotting factors (proteins) • How can this be treated? Potential

problems of treatment?

• Leukemia – excessive production of leukocytes (non-functional)