Human Physiology and Pathophysiology (Lecture) - MODULE 6

Blood  Able to readily squeeze through

capillaries
Blood  Lack nuclei and mitochondria

 Connective tissue Red Blood Cell Counts

 Transports vital substances
 RBC counts are the number of RBCs in a
 Maintains stability of interstitial fluid
cubic millimeter or microliter of blood
 Distributes heat
 It may vary depending on age and health
Blood cells  Typical ranges include
o 4,600,000 – 6,200,000 in males
 Form mostly in red bone marrow and o 4,200,000 – 5,400,000 in adult
are: females
o Red blood cells (RBCs) o 4,500,000 – 5,100,000 in
o White blood cells (WBCs) children
o Platelets (cell fragments)  RBC counts reflect blood’s oxygen
The amount of blood varies with body carrying capacity
size, changes in fluid concentration, changes in Red Blood Cell Production and Its Control
electrolyte concentration and amount of adipose
tissue. Blood is about 8% of body weight. Adult  Low blood oxygen causes the kidneys
blood volume is about 5 liters. and the liver to release erythropoietin
(EPO) which stimulates RBC production
 This is a negative feedback mechanism
=  Within a few days many new blood cells
appear in the circulating blood

Remember:

 Each hemoglobin protein is made up

subunits called hemes, which are what
give blood its red color. More specifically,
the hemes can bind iron molecules and
these iron molecules bind oxygen.
 The blood cells are red because of the
interaction between iron and oxygen.
BLOOD CELLS
HEMOGLOBIN
 Originate in red marrow from
 Tetrametric, two alpha chains and two
hemocytoblasts or hematopoietic stem
beta chains
cells
 Binds a total of 4 oxygen molecules
 Stem cells can then:
 Carries O2 from lungs to tissues
o Give rise to more stem cells
o Specialize or differentiate  Cooperative binding of O2
 Required to increase the solubility of O2
Characteristics of Red Blood Cells in blood

 Erythrocytes Derivatives of Hemoglobin

 Biconcave discs
 Oxyhemoglobin (oxyHb) = Hb with O2
 One-third hemoglobin or:
 Deoxyhemoglobin (deoxyHb) Hb without
o Oxyhemoglobin
O2
o Deoxyhemoglobin

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Human Physiology and Pathophysiology (Lecture) - MODULE 6
 Methemoglobin (metHb) contains Fe3+ 2. Macrophages in the spleen and liver
instead of Fe2+ in heme groups phagocytize damaged RBC
 Carbonylhemoglobin (HbCO) CO binds 3. Hemoglobin from the RBC is decomposed into
to Fe2+ in heme in case of CO poisoning heme and globin.
or smoking. CO has 200x higher affinity 4. Heme is decomposed into iron and biliverdin
to Fe2+ than O2. 5. Iron is made available for reuse in the
 Carbaminohemoglobin (HbCO2) – Co2 is synthesis of new hemoglobin or is stored in the
non-covalently bound to globin chain of liver as ferritin.
Hb. HbCO2 transports CO2 in blood 6. Some biliverdin is converted into bilirubin.
(about 23%) 7. Biliverdin and bilirubin are excreted in bile as
 Glycohemoglobin (HbA1c) is formed bile pigments.
spontaneously by nonenzymatic reaction 8. The globin is broken down into amino acids
with GIc. People with DM have more metabolized by macrophages or released into the
HbA1c than normal (>7%). Measurement blood.
of blood HbA1C is useful to get info
about long-term control of glycemia. WHITE BLOOD CELLS
Dietary Factors Affecting Red Blood Cell
Production Types
 Leukocytes
 Vitamin B12 and folic acid are necessary  Protect against disease
o They are required for DNA  WBC hormones are interleukins and
synthesis, making them colony-stimulating factors which
necessary for the growth and stimulate development
division of all cells  There are five types of WBCs in two
 Iron is also necessary categories
o It is required for hemoglobin o Granulocytes
synthesis  Neutrophils
 Eosinophils
Dietary Factors affecting RBC Production
 Basophils
Substance Source Function
o Agranulocytes
Vitamin B12 Absorbed from DNA synthesis
requires small intestine  Lymphocytes
intrinsic factor  Monocytes
for absorption
via SI TYPES OF ANEMIA
Iron Absorbed from Hemoglobin Type Cause Defect
small synthesis Aplastic Toxic Damaged
intestine; anemia chemicals, bone marrow
conserved radiation
during RBC Hemolytic Toxic RBC
destruction anemia chemicals destroyed
and made
Iron deficiency Dietary lack of Hemoglobin
available for
anemia iron deficient
reuse
Pernicious Inability to Excess of
Folic acid Absorbed from DNA synthesis anemia absorb vitamin immature cells
small intestine
B12
Sickle cell Defective RBC
Major Events in RBC Destruction disease gene abnormally
1. Squeezing through the capillaries of active shaped
tissues damages RBC Thalassemia Defective Hemoglobin
gene deficient; RBC
short-lived

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Human Physiology and Pathophysiology (Lecture) - MODULE 6
Neutrophils  T cells and B cells
 Light purple granules in acid-base o Both important in immunity
(neutral) stain  B cells produce antibodies
 Lobed nucleus  25% - 33% of leukocytes
 Other names
o Segs
o Polymorphonuclear leukocyte Functions of White Blood Cells
o Bands (young neutrophils)  Protect against infection
 First to arrive at infections  These leukocytes can squeeze between
 Phagocytic the cells of a capillary wall and enter the
 54% - 62% of leukocytes tissue space outside the blood vessel
 Elevated in bacterial infections (called diapedesis)

Eosinophils White Blood Cell Counts

 Deep red granules in acid stain  A procedure used to count number of
 Bi-lobed nucleus WBCs per cubic millimeter of blood
o Typically 5,000 – 10, 000 per
 Moderate allergic reactions cubic millimeter of blood
 Defend against parasitic worm  Leukopenia
infestations o Low WBC count (below 5,000)
 1%-3% of leukocytes o Typhoid fever, flu, measles,
 Elevated in parasitic worm infections and mumps, chicken pox, AIDS
allergic reactions  Leukocytosis
o High WBC count (above 10,
Basophils 000)
 Deep blue granules in basic stain o Acute infections, vigorous
 Release histamine exercise, great loss of body
fluids.
 Release heparin
 Differential WBC count
 Less than 1% of leukocytes
o Lists percentages of types of
 Similar to eosinophils in size and shape
leukocytes
of nuclei
o May change in particular
diseases
Monocytes
 Largest of all blood cells
ABNORMAL WBC NUMBERS
 Spherical, kidney-shaped,oval or lobed
WBC Population Illness
nuclei Change
Elevated lymphocytes Hairy cell leukemia,
whooping cough,
 May leave bloodstream to become mononucleosis
macrophages Elevated eosinophils Tapeworm infestation,
 3%-9% of leukocytes hookworm infestation.
Allergic reactions
 Phagocytize bacteria, dead cells, and
Elevated monocytes Typhoid fever, malaria,
other debris tuberculosis
Elevated neutrophils Bacterial infections
Lymphocytes Too few helper T cells AIDS
 Slightly larger than RBC (lymphocytes)
 Large spherical nucleus surrounded by
thin rim of cytoplasm

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 Human Physiology and Pathophysiology (Lecture) - MODULE 6
Gases and Nutrients
 The most important blood gases”
BLOOD PLATELETS o Oxygen
o Carbon dioxide
 Thrombocytes  Plasma nutrients include:
 They are called fragments of o Amino acids
o Simple sugars
megakaryocytes
o Nucleotides
 They lack a nucleus and are roughly half o Lipids
the size of a RBC  Fats (triglycerides)
 There are approximately 130,000 –  Phospholipids
360,000 per cubic millimeter of blood  Cholesterol
 They help repair damaged blood vessels
Nonprotein Nitrogenous Substances
by sticking to broken surfaces
 These are molecules containing nitrogen
but are not proteins
BLOOD PLASMA  In plasma they include:
 Straw colored o Urea – product of protein
 The liquid portion of blood catabolism; about 50% of
nonprotein nitrogenous
 55% of blood volume
substances
 92% water
o Uric acid – product of nucleic
 Function includes transporting nutrients, acid catabolism
gases, and vitamins o Amino acids – product of protein
 Helps regulate fluid and electrolyte catabolism
balance and maintain Ph o Creatine – stores phosphates
o Creatinine – product of creatine
These are the most abundant dissolved metabolism
substances (solutes) in plasma o BUN – blood urea nitrogen;
indicates health of kidney
PLASMA PROTEINS
Protein Percentage Origin Function Plasma Electrolytes
of Total  Plasma contains a variety of these ions
Albumin 60% Liver Helps maintain called electrolytes
colloid osmotic  They are absorbed from the intestine or
pressure released as by-products of cellular
Globulin 36% metabolism
Alpha Liver Transport  They include:
globulins lipids and fat- o Sodium (most abundant with
soluble chloride)
vitamins o Potassium
Beta Liver Transport o Calcium
globulins lipids and fat- o Magnesium
soluble o Chloride (most abundant with
vitamins sodium)
Gamma Lymphatic Constitute the o Bicarbonate
globulins tissues antibodies of o Phosphate
immunity o Sulfate
Fibrinogen 4% Liver Plays a key
role in blood Hemostasis
coagulation  Refers to the stoppage of bleeding
 Actions that limit or prevent blood loss
include:
o Blood vessel spasm
o Platelet plug information
o Blood coagulation

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 Human Physiology and Pathophysiology (Lecture) - MODULE 6
Blood Vessel Spasm  A number of events occur that includes
 Triggered by pain receptors, platelet factor VII, factor X, factor V, factor IV,
release, or serotonin and factor II (prothrombin)
 Smooth muscle in blood vessel contracts  Triggered when blood contacts damaged
blood vessel walls or tissues
Platelet plug formation  This is an example of a positive feedback
 Triggered by exposure of platelets to mechanism
collagen
 Platelets adhere to rough surface to form Intrinsic clotting mechanism
a plug  Chemical inside blood triggers blood
coagulation
1. break in vessel wall  Triggered by Hageman factor XII (found
2. blood escaping through break inside blood)
3. platelets adhere to each other to end of broken  Factor XII activates factor XI which
vessel, and to exposed collagen activates IX which joins with factor VIII to
4. platelet plug helps control blood loss activate factor X
 Triggered when blood contacts a foreign
Blood Coagulation surface
 Triggered by cellular damage and blood
contact with foreign surfaces BLOOD COAGULATION
 A blood clot forms Steps Extrinsic Intrinsic
 This is a: Clotting Clotting
o Hemostatic mechanism Mechanism Mechanism
o Causes the formation of a blood Trigger Damage to Blood contacts
clot via a series of reactions vessel or foreign
which activates the next in a tissue surface
cascade Initiation Tissue Hageman
o Occurs extrinsically or thromboplastin factor
intrinsically
Series of Prothrombin Prothrombin
reactions activator activator
HEMOSTATIC MECHANISMS involving
Mechanism Stimulus Effect several
Blood vessel Direct stimulus to Smooth muscles in clotting factors
spasm vessel wall or to vessel wall contract and calcium
pain receptors; reflexly; ions lead to
platelets release vasoconstriction the production
serotonin, a helps maintain of:
vasoconstrictor prolonged vessel Prothrombin Prothrombin to Prothrombin to
spasm activator and thrombin thrombin
Platelet plug Exposure of Platelets adhere to calcium ions
formation platelets to rough rough surfaces and cause the
surfaces or to to each other, conversion of
collagen of forming a plug Thrombin Fibrinogen to Fibrinogen to
connective tissue causes fibrin fibrin
Blood Cellular damage Blood clot forms as a fragmentation,
coagulation and blood contact result of a series of then joining of;
with foreign reactions,
surfaces activate terminating in the
factors that favor conversion of
coagulation fibrinogen into fibrin.

Extrinsic Clotting Mechanism

 Chemical outside of blood vessel triggers
blood coagulation
 Triggered by tissue thromboplastin
(factor III) (not found in blood)

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Human Physiology and Pathophysiology (Lecture) - MODULE 6
CLOTTING FACTORS Prevention of Coagulation
Clotting Factor Source Mechanism(s)  The smooth lining of blood vessels
I (fibrinogen) Synthesized Extrinsic and discourages the accumulation of
in liver intrinsic platelets and clotting factors
II Synthesized Extrinsic and  As a clot forms fibrin absorb thrombin
(prothrombin) in liver, intrinsic and prevents the clotting reaction from
requires spreading
vitamin K  Anti-thrombin inactivates additional
III (tissue Damaged Extrinsic thrombin by binding to it and blocking its
thromboplastin) tissue action on fibrinogen
IV (calcium Diet, bone Extrinsic and  Some cells such as basophils and mast
ions) intrinsic cells secrete heparin (an anticoagulant)
V Synthesized Extrinsic and
(proaccelerin) in liver, intrinsic Factors that Inhibit Blood Clot-Formation
released by Factor Action Factor Action
platelets Smooth Prevents Antithrombin Interferes with
VII (serum Synthesized Extrinsic lining of activation of in plasma the action of
prothrombin in liver, blood intrinsic blood thrombin
conversion requires vessel clotting
accelator) vitamin K mechanism
VIII Released by Intrinsic Prostacyclin Inhibits Heparin Interferes with
(antihemophilic platelets and adherence of from mast the formation
factor) endothelial platelets to cells and of
cells blood vessel basophils prothrombin
IX (plasma Synthesized Intrinsic wall activator
thromboplastin in liver, Fibrin Absorbs
component) requires threads thrombin
vitamin K
X (stuart-power Synthesized Extrinsic and Blood Groups and Transfusions
factor) in liver, intrinsic
requires  In 1910, identification of the ABO blood
vitamin K antigen gene explained the observed
XI (plasma Synthesized Intrinsic blood type incompatibilities
thromboplastin in liver  Today there are 31 different genes
antecedent) known to contribute to the surface
XII (Hageman Synthesized Intrinsic features of RBCs determining
factor) in liver compatibility between blood types
XIII (fibrin- Synthesized Extrinsic and
stabilizing in liver, intrinsic Antigens and Antibodies
factor) released by  Agglutination – clumping of red blood
platelets cells in response to a reaction between
an antibody and an antigen
Fate of Blood Clots  Antigens – a chemical that stimulates
cells to produce antibodies
 After a blood clot forms it retracts and  Antibodies – a protein that reacts against
pulls the edges of a broken blood vessel a specific antigen
together while squeezing the fluid serum
from the clot ABO Blood Group
 Platelet-derived growth factor stimulates  Based on the presence or absence of
smooth muscle cells and fibroblasts to two major antigens on red blood cell
repair damaged blood vessel walls membranes
 Plasmin digests the blood clots o Antigen A
 A thrombus is an abnormal blood clot o Antigen B
 An embolus is a blood clot moving
through the blood vessels

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Human Physiology and Pathophysiology (Lecture) - MODULE 6
Blood Type Antigen Antibody
A A Anti-B
B B Anti-A
AB A and B Neither anti-A
nor anti-B
O Neither A nor Both anti-A
B and anti-B

Blood Type Preferred Permissible

of Recipient Blood Type Blood Type
of Donor of Donor (In
an Extreme
Emergency)
A A O
B B O
AB AB A, B, O
O O No alternate
types

Rh Blood Group
 The Rh blood group was named for the
rhesus monkey
 The group includes several Rh antigens
or factors
 Rh positive – presence of antigen D or
other Rh antigens on the red blood cell
membranes
 Rh negative – lack of these antigens
 The seriousness of the Rh blood group is
evident in a fetus that develops the
condition erythroblastosis fetalis or
hemolytic disease of the newborn

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