Chapter 17 Anatomy and Physiology notes

Blood is an extracellular fluid

Features of blood

1. Transport- gases, nutrients, ions, hormones to promote cellular respitration through veins, arteries, and
capillaries
a. Removes CO2 and metabolic waste from tissues
2. Buffering of pH, temperature, and osmolarity
3. Defense against pathogens and dead/damaged tissues
4. Clotting- of blood to prevent fluid loss through damaged circulatory vessels

Blood is connective tissue

Blood only makes up a small fraction of extracellular fluid

Blood volume- average around 5-6 L in men and 4-5 L in women

Blood consists of plasma and formed elements

 A blood sample consists of 46-63% plasma and 37-54% formed elements

o Plasma- is the liquid fraction of the blood, and is more than 90% water by volume. excellent
temperature buffer. Plasma is best described as a colloid solution
 All ions, including Na+, K+, Cl-, and Ca2+ are found in the plasma fraction of blood.
Bicarbonate (HCO3–) is also found in the plasma, and is an important buffer over the
range of physiological pH. 
 Plasma composition
 Plasma proteins (7%)
o Albumin (60%) prevents welling and shrinkage of cells, osmotic
pressure,; transport lipids, hormones and steroids
 highly abundant plasma proteins produced by the liver.
o Globulin (35%)- transport immunoglobulins (antibodies) and other
globulins, defends the body against foreign pathogens
o Fibrinogen (Clotting factor. 4%)- prevents fluid loss during injury and
is essential for blood clotting
o Regulatory proteins (<1%): enzymes, proenzymes, hormones
o Other solutes (1%)
 Electrolytes- plasma salt
 Organic nutrients-lipids, carbohydrates, and amino acids
 Organic wastes- urea, creatine, bilirubin
o Water (92%)- transports organic and inorganic molecules, formed
elements and heat.
o Formed Elements
 Platelets- fragments of megakaryocytes critical for clotting
 Leukocytes
 Neturophils(50-70%)
 Eosinophils (2-4%)
 Basophils(<1%)
 Lymphocytes (20-30%)
 Monocytes(2-8%)
 Red blood cells (99.9%)
formed elements - All the components of blood not contained within the plasma and are either cells (red and white
blood cells) or cell fragments (platelets).

buffy coat.- whereLeukocytes and thrombocytes are located in a centrifuged blood suspension just below the plasma
in a layer

 In a healthy individual, the buffy coat only takes up a very small volume, since platelets and leukocytes
combined make up only about 5% of the formed element fraction.

Erythrocytes account for 95% of the entire formed element fraction and more than 40% of the volume of whole
blood and almost one third of all of the cells inside your body.

 The packed volume of erythrocytes following centrifugation is known as the hematocrit

o Hematocrit is expressed as the total percentage of blood volume sampled
o Normal hematocrit is 40.7%-50.3% for men and 36.1-44.3% for women, any deviation is usually a
sign of something wrong.
o Can serve as a reference for someone’s capacity to carry oxygen.

Polycythemia- increase in the number of red blood cells

Leukemia- excessively high number of white blood cells

Complete blood count (CBC) is a group of tests that evaluate the cells that circulate in blood, including red blood
cells (RBCs), white blood cells (WBCs), and platelets (PLTs).

 The CBC can evaluate your overall health and detect a variety of diseases and conditions, such
as infections, anemia and leukemia.

Mean Corpuscular Volume (MVC)- measures the average size of your red blood cells

White blood cell (WBC) count is a test that measures the number of white blood cells in your body

Platelet blood count (PLT) is a blood test that measures the average number of platelets in the blood. 

Mean corpuscular hemoglobin concentration (MCHC) It's a measure of the average concentration of hemoglobin
inside a single red blood cell.

Hemoglobin (Hgb) test measures how much hemoglobin your red blood cells contain.

Red blood cell distribution width (RDW) blood test helps measure variation in red blood cell volume and size.

A red blood cell is biconcave, which gives them the inner-tube like appearance where the edges of the cell are
significantly thicker than the center

 This unique shape of red blood cells allows them to bend, fold, and “stack” to prevent blockages in these
tiny vessels. Moreover, the shear stress created by flexing promotes the release of signaling molecules like
ATP, which help to increase the radius of the vessels the cells are traveling through.
 In the orthochromatic erythroblast stage, the cells ejects its organelles and hemoglobin becomes the most
abundant protein in the cell, making it have a biconcave appearance.

Erythropoiesis- production of red blood cells.

 Develops from erythropoietic stem cell to mature red blood cell.

 It is stimulated by decreased O₂ in circulation, which is detected by the kidneys, which then secrete the
hormone erythropoietin.
 Can also be stimulated by testosterone
 Steps:
 1. Hematopoietic stem cell
2. Myeloid stem cell
3. Proerythroblast
4. Basophilic erythroblast
5. Polychromatic erythroblast
6. Orthochromatic erythroblast
7. Reticulocyte
8. Erythrocyte

Hematopoietic stem cells are located inside red bone marrow 

 a hematopoietic stem cell can become either a red blood cell or a white blood cell
 These changes are often induced by hormones and cytokines binding to a specific receptor on the stem cell
membrane.

Reticulocytes are nearly mature erythrocytes released into circulation with a nucleus and it is quickly converted to a
mature erythrocyte by losing the nucleus

 elevated levels of reticulocytes are in response to large blood losses.

 Blood loss results in a greater movement of reticulocytes into blood as a compensatory response.

Anemia- any blood disorder characterized by a failure of the body to maintain an adequate O2 supply to the tissues

 has many potential underlying causes and therefore many subtypes.

Anemia that is specifically due to vitamin B deficiency is known as pernicious anemia, and it is part of a larger
subcategory known as megaloblastic (macrocytic) anemias. 

The MCV of someone afflicted by pernicious anemia would be lower in comparison to someone who received
ample B12.

Hemoglobin is a globular tetrameric protein

 adult hemoglobin is formed from two alpha chains and two beta chains, whereas fetal hemoglobin is
formed from two alpha and two gamma chains(gamma chain eventually becomes beta).
 Fetal hemoglobin has a higher affinity for oxygen
 The ability of each chain to bind O2 comes from the heme group located at the center of its three-
dimensional structure. Each heme group contains an iron (Fe2+) atom that reversibly binds to a single
oxygen atom.

Haldane effect- CO2 binding is favored by deoxyhemoglobin. Hemoglobin bound to CO2 is known

as carbaminohemoglobin. Importantly, CO2 does not bind competitively with O2, since it does not bind to iron.

Bohr effect-the binding of CO2 molecules (or protons that are formed from the dissociation of carbonic acid) to
hemoglobin does promote oxygen release.

iron deficiency anemia- usually occurs when iron loss temporarily exceeds iron intake. reduces the oxygen carrying
capacity of the blood. This form of anemia is quickly corrected by eating iron-rich foods or taking an iron
supplement. MCV low and MCHC low

microcytic anemias- Low presence of hemoglobin, it causes the overall size of the cell to be abnormally small (low
MVC). Thalassemia.
Thalassemia- Mutations in hemoglobin leading to conformational changes in the protein that will impact its ability
to bind and transport oxygen. May occur on either chain (e.g. beta chain thalassemia).

Macrocytic anemia- identified by low hemoglobin but high MCV

Normocytic anemia- Low hemoglobin but normal MCV (might also be present in leukemia though, indicated by
elevated WBC)

Sickle cell disease (SCD) caused by a single point mutation in the beta globin gene, which results in mis-folding of
the beta chain.

 normal adult hemoglobin exists as a monomer, sickle hemoglobin (HbS) polymerizes into rods because of
interactions between the misfolded beta chains.
 these chains become long enough to change the cells from a flexible biconcave shape to a rigid “sickle” or
crescent shape – this makes the cells prone to apoptosis and interferes with O2 unloading by decreasing the
surface to volume ratio.
 Sickled red blood cells also have increased expression of adhesion receptors on their plasma membranes,
which makes them “sticky”. are prone to clogging small vessels, especially during the fight or flight
response.
 Causes the obstruction of blood flow also causes severe pain and increases the risk of stroke.
 In a patient with sickle cell syndrome, the excessive levels of altered and damaged erythrocytes leading to a
physical blockage of capillaries and arterioles in the spleen, leading to reduced oxygen and nutrients to
spleen cells. This ultimately leads to progressive losses of spleen tissue, until the spleen completely dies
and is absorbed. The MRI would reveal the complete lack of the spleen - or asplenic. The spleen is a
primary lymphatic organ and its loss would decrease the ability of the immune system to repel infections by
bacteria and viruses.

When red blood cells reach the end of their lifespan, they are engulfed by macrophages, and hemoglobin is carefully
degraded into its components, which have unique fates:

 Proteins are reduced into their component amino acids. The heme group has a more complex fate, and is
converted into biliverdin and then to bilirubin. As heme is converted, the pigment changes color from red
(heme) to green (biliverdin) to yellow (bilirubin).
 Bilirubin is released by the macrophages into the plasma, and most of it will be transported by albumin to
the liver where it is incorporated into bile.
o In the intestine, gut bacteria further convert bilirubin, resulting in a pigment called stercobilin that
gives excreted feces its characteristic brown color. A small amount of bilirubin is excreted in the
urine, which gives urine its characteristic yellow color.
 The iron liberated from the heme group is recycled back into the bone marrow, the site of erythropoiesis.
When released from macrophages, iron binds to a plasma globulin called transferrin, which transports it
safely through the blood to the bone marrow.
o Excess iron is stored in the tissues in complex with the proteins ferritin and hemosiderin, until it is
needed for erythropoiesis.

Hemolysis is a term used to describe the premature rupturing of erythrocytes. 

Granulocytes, which contain membrane bound cytoplasmic granules that give the cytoplasm a “spotted” appearance.

Agranulocytes, which lack granules in the cytoplasm.

Leukocytes:

 Leukocytes are nucleated, and in some cases bi-lobed nuclei have membrane bound organelles, and lack
hemoglobin.
 Leukocytes move through amoeboid motion, created by extending cytoplasmic projections forward, and
then moving the posterior portion of the cell forward to “catch up”. This creates an inchworm or “ooze”
like movement.
 This movement is the result of chemotaxis, or in response to chemicals released from dying cells, or other
blood cells that serve as an attractant.
 Leukocytes interact with the endothelial cells that form circulatory vessels by forming transient bonds
using adhesion receptors. This is called margination.
 Leukocytes have the unique ability to leave the blood and enter tissues. This process of diapedesis (also
known as extravasation) involves leukocytes becoming thin and elongated to “slip” between adjacent
endothelial cells.
 White blood cells make up less than 1% of the total blood volume.
 Neutrophils (50-70% abundance)
o Granulocyte
o killers of bacteria, their secretory granules contain hydrolytic enzymes and specialized
antimicrobial molecules called defensins (cationic (positively charged) proteins that bind to
microbial cell membranes and create pores, which disrupt the nutrient, ion, and osmotic balance in
the bacterial cell).
o release lysozyme, an enzyme capable of digesting the bacterial cell wall.
o neutrophil secretions mix with components inside bacteria, they generate free radicals and
peroxides that destroy the cell in a process known as oxidative burst.
o In response to an infection, neutrophil levels spike and neutrophils migrate to the infected area to
fight the foreign invader.
o Neutrophils are large and polymorphonuclear (they have a nucleus that typically contains 2–6
lobes).
o Stained purple
 Lymphocytes (25-40% abundance)
o Agranulocyte
o are divided into two subcategories, and both help the immune system to recognize and target
specific pathogens. B-lymphocytes are responsible for producing antibodies; T-lymphocytes help
to defend the body against abnormal, cancerous, and virus-infected cells.
o smallest leukocyte, with most of their cytoplasmic volume being occupied by a single nucleus.
Lymphocytes lack granules, and stain dark blue and purple.
 Monocytes (4-8% abundance)
o Agranulocyte
o defend the body against a wide variety of foreign invaders, including bacteria and viruses.
o They exit the circulation and transform into macrophages, which engulf bacteria
through phagocytosis. also important for activating lymphocytes
o Inflammatory macrophages move through positive chemotaxis toward chemicals released from
damaged cells and help to contain the damage by engulfing cellular debris.
o Non-inflammatory macrophages reside in connective tissue throughout the body and help to
prevent pathogens from entering the bloodstream.
o Monocytes are the largest leukocytes (consistent with their phagocytic function). They have a U-
shaped nucleus that resembles elbow macaroni, lack cytoplasmic granules, and stain dark blue and
purple.
 Eosinophils (2-4% abundance)
o Granulocyte
o secrete four distinct cationic proteins (major basic protein, eosinophil cationic protein, eosinophil
derived neurotoxin, and eosinophil peroxidase)
 eosinophil secretions have very little impact on bacteria but are important for combatting
o
multicellular parasites, including flatworms and roundworms. However, these secretions can also
damage our own body tissues.
o regulate inflammation by secreting enzymes that degrade histamine
o likely explanations for the role that eosinophils play in hypersensitivity reactions including
allergies and asthma.
o Eosinophils are large leukocytes with bi-lobed nuclei, which resemble over-the-ear headphones.
They have very large cytoplasmic granules, and stain bright red with the acidic dye eosin.
 Basophils (<1% abundance)
o Granulocyte
o their secretions do not directly target foreign cells.
o Their granules contain histamine, serotonin, heparin, and prostaglandins, which mediate
inflammation and changes in blood flow.
o Like eosinophils, basophils also play an important part in some allergic responses
including anaphylaxis.
o Basophils have bi-lobed nuclei, contain large cytoplasmic granules, and stain darkly blue with
basic dyes.

Leukopoiesis

formed in bone marrow located in bones in adults and hematopoietic organs in the fetus.

1. Myeloid stem cell

2. Myeloblast
3. Neutrophilic promyelocyte
4. Neutrophilic myelocyte
5. Neutrophilic band cell
6. Neutrophil

Lymphocytes originate from lymphoid stem cells, which arise from hematopoietic stem cells.

 Immature lymphocytes in the bone marrow are referred to as lymphocyte precursor cells.

 B-lymphocytes remain inside the bone marrow to mature (this process is covered in the chapter on the
Immune System).
 T-lymphocytes migrate to the thymus to mature (this process is also covered in the chapter on the Immune
System).

When analyzing the CBC of someone with leukemia

 Blood group
antigens are
inherited in
an autosomal
dominant man
ner, it is
possible to
receive an “A”
allele from
your mother
and a “B”
allele from
your father, or
vice versa.
This means
that you can
have both
antigens.

Individuals
that express
both Antigen
A and Antigen B have blood type “AB”. Only about 5% of the US population has type AB blood.

Individuals that lack both Antigen A and B have blood type “O”. This is the most common blood type about 45% of
the US population has type O blood.

This additional qualifier, positive or negative, provides a classification in the second major blood group, based upon
an antigen known as the Rhesus (commonly abbreviated Rh) factor. Because this trait is inherited independently of
the other blood group antigens, they are not mutually exclusive. This means that:

 An individual with Rh factor has a positive blood type – A positive, B positive, AB positive, or even O
positive (remember that “O” only means an individual is missing A or B antigen). More than 85% of the
population has Rh factor, making it very common.
 An individual without Rh factor has a negative blood type – A negative, B negative, AB negative, or O
negative.

Donor compatibility rules for the ABO system are as follows:

 Individuals with A blood type can donate to individuals with A or AB blood, since these recipients lack
anti-A antibodies.
 Individuals with B blood type can donate to individuals with B or AB blood, since these recipients lack
anti-B antibodies.
 Individuals with AB blood type can donate only to individuals with AB blood, since all other recipient
blood types have either anti-A or anti-B antibodies. 
 Individuals with O blood type can donate to all other blood types, since this donated blood lacks A and B
antigens. For this reason, individuals with type O blood are often referred to as universal donors.

Recipient compatibility rules for the ABO system are as follows:

  Individuals with A blood type can receive blood from individuals with A or O blood, since these recipient
individuals lack anti-A antibodies but have anti-B antibodies.
 Individuals with B blood type can receive blood from individuals with B or O blood, since these recipient
individuals lack anti-B antibodies but have anti-A antibodies.
 Individuals with AB blood type can receive blood from individuals with A, B, or O blood, since these
recipients do not have anti-A or anti-B antibodies. For this reason, people with AB blood type are referred
to as universal recipients.
 Individuals with O blood type can only receive blood from donors with type O blood, since they have anti-
A and anti-B antibodies.

Rhesus factor can also elicit an immune response because individuals with negative blood types can produce
antibodies against Rhesus factor (known as anti-Rh or Anti-D).

 However, unlike anti-A and anti-B antibodies, anti-Rh antibodies are not always present in Rh negative
individuals.
 This is because antibody production requires sensitization (Exposure of the immune system to a foreign
antigen.)

Hemolytic disease of the newborn 

 Rh incompatibility between a mother and her developing fetus because she is Rh negative and carrying a
Rh+ child
 Fetal erythrocytes are normally separated from the mother's circulation by the placenta
 During late pregnancy and child birth, however, fetal erythrocytes may escape into the mother's circulation
and sensitize her immune system to produce anti-Rh+ antibodies.
 Most women do not make anti-Rh before the birth of their first child, but during repeat pregnancies (with
more Rh+ children) maternal antibodies cross the placenta and react with the fetal erythrocytes causing
their destruction and miscarriage.
 The immunoglobulins of anti-Rh antibodies are smaller than anti-A or anti-B antibodies, which is why
hemolytic disease does not occur with ABO incompatibility.
 Mothers are treated by injection with anti-Rh factor antibodies, which will destroy any Rh+ blood cells in
the mother’s circulation before they can “wake” her immune system.
Platelets are the final formed element found in the blood

 platelets are not cells, but actually fragments of a very large cell known as a megakaryocyte that exists in
the bone marrow.
 Megakaryocytes are also derived from myeloid stem cells in response to hormonal signals (e.g.
thrombopoietin), and slowly shed membrane bound fragments (the platelets) as they mature.
 After releasing thousands of platelets, megakaryocytes are engulfed by macrophages and destroyed.
 Platelets coordinate the formation of blood clots, which “patch” damaged vessels until they can be repaired.
This process of stopping blood loss is known as hemostasis.

The three phases of hemostasis are:

1. The Vascular Spasm Phase, which occurs immediately after a vessel is damaged.

a. During the vascular spasm phase, smooth muscle in the vessel constricts to limit blood. This is
initiated by chemical messengers like endothelin, which is released from damaged endothelial
cells.
b. Other released molecules serve as “damage signals” including tissue factor and ADP, which
attract leukocytes, activate platelets, and initiate the process of clot formation.
c. To promote the interaction between these cells and the endothelium, cell to cell adhesion
molecules are upregulated on the endothelial membranes, making them “sticky”.
2. The Platelet Phase begins with the activation of platelets that are arriving at the site of damage and
adhering to the sticky endothelium.
a. Activated platelets are also “sticky” and release chemical messengers including Thomboxane
A2, ADP, Ca2+ ions, and clotting factors. 
 b. These chemical messengers activate more platelets, causing the platelet phase to proceed very
quickly. The major result of the platelet phase is the formation of a platelet plug, which is usually
sufficient to temporarily stop blood loss (assuming there is no major damage to the vessel).
Activated platelets also promote wound healing by releasing platelet derived growth factor, which
stimulates cell division.
3. The Coagulation Phase is the final phase of hemostasis, characterized by reinforcement of the platelet
plug by a web-like protein mesh formed from fibrin. Fibrin is an insoluble protein formed from the soluble
plasma protein fibrinogen. The fibrin entangles platelets, erythrocytes, and leukocytes to “dam” off the site
of damage until it is repaired.
4. Clot Retraction is not a phase per se, but after the fibrin mesh has formed, platelets will begin to contract
in order to make the clot more compact and pull the edges of the wound closer together.

Converting soluble fibrinogen into insoluble fibrin requires catalysis by an enzyme known as thrombin, which is a
clotting factor.

 This means that we are now going to talk about the different pathways (common, extrinsic, and intrinsic)
that lead to the activation of clotting factors. Clotting factors are synthesized in the liver, a process that is
dependent on vitamin K.
 To prevent accidental clot formation, clotting factors are synthesized and circulated as zymogens.