blood dr. anderson gcit. components of blood functions distribution of materials to the tissues in...

Blood

Dr. AndersonGCIT

Components of Blood• Functions

• Distribution of materials to the tissues in the body• o2/co2 transport• hormones• nutrients• metabolic wastes

• Regulation• solute concentration• body temperature• pH Balance• Fluid volume (water concentration)

• Protection• clotting• immune response

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

blood volume)• Mostly water• Salts• Hormones• Sugar• Proteins and amino acids

• Formed elements (cells)• Leukocytes – White blood cells (1% of blood volume)• Erythrocytes – Red blood cells (~44% of blood

volume)• Platelets – help in forming clots

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• Cations – Na+, K+, Mg+, Ca+

• Anions – Cl-, PO4-, SO4

-, CO3-

•Respiratory Gases• CO2, O2

Formed Elements• Erythrocytes – Red Blood Cells (RBC’s)

• Biconcave cells• NO Nucleus!• Mostly composed of hemoglobin molecules• They do NOT use O2 for respiration (use anaerobic

respiration instead)

• Why are all of these things adaptive??

Hemoglobin• Quaternary protein molecule made

of two functional parts

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

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

Sickle Cell Anemia• In sickle-cell anemia, 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

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

Will we lose our appendix through evolution- and why?

Anemia• A decrease in the capacity of the blood to carry oxygen to the tissues• Leads to general fatigue and malaise• Increased cardiac output

• What factors can cause anemia?

1. Lack of Iron (nutrition)

2. Hemoglobin production (nutrition)

3. Hemorrhage/ disease

Leukocytes• Specifically engage different invaders of the body

(pathogen types)• Divided into granulocytes and agranulocytes due to

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

“grainy” appearance• Agranulocytes – few or no organelles

Specific Jobs of Leukocytes - Granulocytes

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

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

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

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• Destroy infected 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 phagocytose bacteria and other invading pathogens

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

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

010002000300040005000600070008000

Differential WBC Count

NormalInfectedCe

lls/u

l

What type of infection does this person have?

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

Origins - Erythropoiesis•Blood cells are made from stem cells 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

Dr. A

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 “non-self” organisms/chemicals• Antigens on bacteria, fungi, protozoans, other pathogens

• People with different blood types have 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

YAnti-A

Anti-B

YAnti-A AND Anti-B

None

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” 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

• 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

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 factors

• Platelets stick tenaciously to the collagen exposed in damaged blood vessels• A large protein (von Willebrand factor) links platelets at the plug to each other

and to the collagen in the vessel wall• ADP and serotonin release 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 smooth muscle

and endothelial cells that repair the damaged vessel

• An activated enzyme (plasmin) 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• Thrombocytopenia – 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?