02/12/2016

General functions:
Buffers pH
L evels Temperature
BLOOD PHYSIOLOGY O2 transport
Osmosis
Defense
Angelie Antoinette Montines, PTRP

Blood Components: RED BLOOD CELLS

2.FORMED ELEMENTS (45%) - Erythrocyte
1. PLASMA (55%) - RBC - Erythropoiesis
- Water (90%) - WBC ** Hematocrit (Hct) ?
Normal: 40-45%
- Erythropoietin
- Electrolytes - Platelets
- Nutrients - Albumin
Structure:
- Fibrinogen
- Gamma 3. BUFFY COAT (<1%) 1. Biconcave
Globulin
- Leukocyte s 2. Pliable
- Platelets 3. Lacks a nucleus and organelles

Shape and Size RED BLOOD CELLS

“PoBRE”
• Biconcave discs Functions: Formation:
- Transport O2
• Diameter: 7.5 micrometers - Lifespan:
- Acid – base buffer - Important for maturation:
• Thickness: 1.9 micrometer Normal values: - Vit B12
• Center: 1 micrometer - M: 5.2 m (5.2 – 6.5m) - Folic acid
- Deficiency?
- F: 4.7m (4.7 – 5.5m) - Death:
Production: - Graveyard:
- embryo: - iron?
- Hgb?
- Middle trimester (AOG):
- After birth: Q: What regulates the number
of RBC the most?

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Maturation of RBC Role of Erythropoietin (EPO)

• Folic Acid • Formed in the kidneys; the remainder formed mainly in the liver
• Vit B 12 (Cyanocobalamin) • Tissue oxygenation is the most essential regulator of erythopoiesis.
- deficiency: failure of nuclear maturation and cell division • Conditions that can cause quantity of oxygen to decrease: anemia,
- Failure to proliferate and production of macrocytes (Maturation failure) very high altitude, cardiac failure, lung diseases.
- Malabsorption of Vit B12 • Formed in what organ?
- Deficiency of Folic Acid • Important effect is to stimulate production of proerythroblasts from
hemapoietic stem cells.

IRON METABOLISM Transport and Storage of Iron

• Important in the formation of hgb • Iron  absorbed from SI  combines with blood plasma with a beta
• Total quantity of iron in the body: 4 gms globulin, apotransferrin  transferrin  plasma
• Transferrin binds with receptors in the cell membranes of
erythroblasts in the bone marrow  ingested into the erythroblast
(endocytosis)
• Lack of transferrin  failure to transport iron  HYPOCHROMIC
ANEMIA (few RBCs with very little hgb)
• Dead and destroyed RBCs  hgb is released  iron is liberated 
stored or reused

Lifespan and Destruction Pathologies:

• RBC normally circulate ~120 days before being destroyed
Overproduction: Underproduction:
• Cytoplasmic enzymes 1.POLYCYTHEMIA VERA 1.ANEMIA
• Pliability (ERYTHREMIA) 1.BLOOD LOSS ANEMIA
• Membrane transport
2.SECONDARY POLYCYTHEMIA 2.APLASTIC ANEMIA
• Ferrous state
(PHYSIOLOGIC) 3.SICKLE CELL ANEMIA
• Prevent oxidation
2.NUTRITIONAL ANEMIA
• Spleen (3micrometers) - self-destruct 1.Fe – DEFICIENCY ANEMIA
2.PERNICIOUS ANEMIA
3.FOLIC ACID ANEMIA

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Hematopoiesis
• Blood formation
• Occurs in bone marrow of axial skeleton, girdles and proximal
epiphyses of humerus and femur
• Hematocytoblast (Pluripotent Hematopoietic Stem Cell)
• Give rise to all formed elements
• Hormones and growth factors push the cell to a specific pathway of blood cell
development

WHITE BLOOD CELLS

“Never Eat Banana, (you’ll) Look-like Monkey”

Granular Agranular
1.Neutrophils – most abundant 1.Lymphocytes – “memory cells”
- lifespan: 2.Monocytes
2.Eosinophils - parasitic infection - mature:
3.Basophils – allergic reactions - lifespan:
- common with most cells in CT
- Have cytoplasmic granules
Normal:
5,000 – 10,000
4,800 – 10,800
(7,000)

• FUNCTIONS:
1. Inflammatory reaction Lifespan of WBCs
• GRANULOCYTES:
2. Immune response – 4-8 hrs in the blood
– 4-5 days in the tis s ues
– Serious tis s ue infection  life is s hortened to only a few hours

• MONOCYTES
1. INFLAMMATORY REACTION – 10-20 hours in the blood before wandering
– In the tis s ues  s well  macrophages  can lives for months or years unles s des troyed during phagocytos is
- Neutrophils, macrophages • LYMPHOCYTES
a. Stimulus: tissue injury (or foreign bacteria) – Circulate along the lymph from the lymph nodes
– Few hrs  tis s ues by diapedes is  re-enter the lymph  blood  again and again
– Life s pan of months to years

• PLATELETS
– Totally replaced approximately once every 10 days
– 30,000 platelets are formed each day/ microliter of blood
b. Lines of defense (4)

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Defensive Properties of Neutrophils and

Monocytes-Macrophages Diapedesis
• Squeeze through the pores of the blood vessels
• NEUTROPHILS
– Attacks and destroys bacteria and viruses
• MONOCYTES
– Immature cells that have very little ability to fight infectious agents
– Once in the tissues  swell  macrophages  extremely capable of combating
disease agents

Ameboid motion Chemotaxis

• Can move at velocities as great as 40µm/min
• Chemical substances in the tissues causing both neutrophils and
macrophages to move toward the source of chemical
• Inflammation  dozen different products are formed  chemotaxis
• These includes:
– Bacterial toxins
– Degenerative products of inflamed tissues
– Reaction products caused of complement complex
– Reaction products caused by clotting in the inflamed area

PHAGOCYTOSIS
• Most important function of neutrophils and macrophages
• Phagocytes must be selective
• Selective procedures:
• Surface of particle is rough
• No protective coats, strongly electrically charged
• Specific means of recognizing certain foreign materials (immune system)

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Phagocytosis by Neutrophils Phagocytosis by Macrophages

• Attaches 1 stto the particle • Phagocytize as many as 100
• Projects pseudopodia in all bacteria
directions around the particle, • Can engulf much larger
meeting each other on the opposite particles, even RBCs or
side and fuse  enclosed chamber malarial parasites
• Chamber invaginates to the inside of • Can extrude the residual
the cavity  phagocytic vesicle products and often survive
(phagosome) many more months
• Can phagocytize 5-20 bacteria

• Enzymatic Digestion of the Phagocytized Particles MONOCYTE-MACROPHAGE SYSTEM AND THE

• Lysosomes fuses with phagocytic vesicles
• Dumping of many digestive enzymes and bacterial agents into the vesicles 
RETICULOENDOTHELIAL SYSTEM
Digestive vesicle

• Macrophages are mobile cells that are capable of

wandering through the tissues
• Macrophages may become attached to the tissues and
remains attached for months or perhaps even years unless
they are called to perform specific protective functions
• (+) Stimulation  break away from their attachments 
mobile  chemotaxis

Pathologies PLATELETS
1. LEUKEMIA – bone marrow produces very few WBC • Normal: 150 – 450,000/mm
2. LEUKOPENIA • Thrombocyte
1. LYMPHOCYTIC LEUKEMIA • Structures: a. fatty
2. MYELOGENOUS LEUKEMIA b. sticky
c. contractile (actin & myosin)

• Function: clot
thrombocytosis
thrombocytopenia (any viral infection)

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Formation CLOTTING FACTORS:

“Father Please Tell Cupid Love Should Always Be Sweet, Caring and Devoted F.”
(1)stimulus: 1. FIBRINOGEN 8. A
2. PROTHROMBIN 9. B
3. THROMBOPLASTIN 10.STUART
4. CALCIUM 11.C
(2)Prothrombin activator 5. LABILE 12.D (HAGEMAN)
7. STABLE 13.FIBRIN

Pathologies INNATE IMMUNITY

1. THROMBOCYTOPENIA - platelet count • General process of resisting almost all types of organisms or toxins.
• Eg. Epistaxis, petechiae, ecchymosis, melena Includes the following;
• Causes: cancer, dengue, vit K deficiency
• Phagocytosis of bacteria and other invaders by WBCs and cells of the tissue
2. THROMBOSIS - platelet count macrophage system
• Causes: immobilization, atherosclerosis • Destruction by the acid secretions of the stomach and by the digestive
• Clotting of BV  thrombus  embolus enzymes of organisms swallowed into the stomach
3. HEMOPHILIA • Resistance of the skin to invasion by the organisms
• “Bleeder’s Dse • Presence in the blood of certain chemical compounds that attach to foreign
• M>F; X- linked recessive organisms or toxins and destroy them
• A. Hemophilia A
• B. Hemophilia B
• C. Hemophilia C

ACQUIRED IMMUNITY TWO BASIC TYPES OF ACQUIRED IMMUNITY

• Extremely powerful specific immunity against individual invading • HUMORAL IMMUNITY OR B CELL IMMUNITY
agents • Body develops circulating antibodies
• Forms antibodies and activated lymphocytes that attack and destroy • CELL MEDIATED IMMUNITY OR T CELL IMMUNITY
the specific organisms or toxins • Formation of large numbers of activated lymphocytes

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ROLE OF LYMPHOCYTES IN ACQUIRED

ANTIGENS IMMUNITY
• Foreign organism or toxin • Lymphocytes are located in the lymph nodes and in
• Proteins or large special lymphoid tissues such as spleen, submucosal
polysaccharides areas of GIT and bone marrow
• Initiates acquired • Lymphoid tissues are distributed in the body to
immunity intercept the invading organisms or toxins before they
can spread too widely.

• B lymphocytes enlarge 
HUMORAL IMMUNITY AND THE ANTIBODIES Lymphoblast
• Further differentiates to
plasmoblasts, which are
• FORMATION OF ANTIBODIES BY PLASMA CELLS the precursors of plasma
• Prior to exposure to antigens, the clones of B lymphocytes remains dormant cells
in the lymphoid tissue • Mature plasma cells
• Upon entry of the foreign antigen, the lymphoid tissue macrophages produces gamma
phagocytize the antigens and presents it to the adjacent B lymphocytes globulins antibodies at a
• Antigen is also presented to the T cells, and activated “helper T cells” also rapid rate (2000
contributes to the activation of B lymphocytes molecules/second for
each plasma cell)
• Antibodies are secreted
into the lymph and are
carried to the circulating
blood

• FORMATION OF MEMORY CELLS

• Subsequent exposure to the same antigen will cause a
Classes of Antibodies
much more rapid and much more potent antibody
response • IgM, IgG, IgA, IgD, and IgE
• Primary response: First exposure to a specific antigen • Ig = Immunoglobulin
• Secondary response: occurs after the second exposure to
the same antigen
• More potent, and forms antibodies for many months

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Mechanisms of Actions of Antibodies TYPES OF T CELLS AND THEIR FUNCTIONS

• 2 Different ways to protect the body: • HELPER T CELLS
• Direct attack on the invader • Most numerous
• Ways to inactivate the invading agent: • Major regulator of virtually all immune functions
• Agglutination: Bound together into a clump • Forms a series of protein mediators, called lymphokines that acts on the other
• Precipitation: Antigen and antibody becomes so large that it is rendered insoluble and
precipitates cells of the immune system and bone marrow cells
• Neutralization: Antibodies cover the toxic sites of the antigenic agent • Interleukin 2-6, GM-Colony stimulating factor, Interferon-ý
• Lysis: Attack membranes of cellular agents and causing rupture to the cell
• Activation of the complement system
• Amplifies effects of antibody attack

• CYTOTOXIC T CELLS • SUPPRESSOR T CELLS

• Direct attack cell • Capable of suppressing the
• Capable of killing functions of both cytotoxic and
microorganisms and at helper T cells
times even some of the • Regulates the activities of the other
body’s own cells cells, keeping them from causing
• “Killer cells” excessive immune reactions that
• Also plays an important role might be severely damaging to the
in destroying cancer cells, body
heart transplant cells, or • Plays an important role in limiting
other types of cells that are the ability of the immune system to
“foreign” to the persons’ attack a person’s own body tissues
own body called immune tolerance
• Regulatory T cells: Helper and
Suppressor T cells

TOLERANCE OF THE ACQUIRED IMMUNE Role of Suppressor T cells in the Development

SYSTEM TO ONE’S OWN TISSUES of Tolerance
• Immune mechanisms normally “recognizes” a person’s own tissues as • In cases of autoimmune reaction:
being completely distinctive from those of invaders, and his immune • Suppressor T cells functions to counteract the effects of autoimmune
system forms very few antibodies or activated T cells against his own antibodies as well as sensitized helper T cells and sensitized cytotoxic T cells,
antigens thus blocking the immune attack on the tissue
• Not entirely clear
• Self-tolerance to the body’s own tissues

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Failure of the Tolerance Mechanism –
Autoimmune Disease
• Loss of immune tolerance to their own tissues
• Occurs to a greater extent the older a person becomes
• Occurs after destruction of some of the body’s tissues, which releases
considerable quantities of antigens that circulate in the body
• Some of these antigens seem to combine with other proteins, such as
bacteria or viruses to form a new type of antigen that can then cause
immunity
• Then activated T cells and antibodies attack the bodys’ own tissues
Vaccination
• Used to cause acquired immunity against specific diseases
• Injecting dead organisms that are no longer capable of
causing disease but which still have their chemical
antigens
• Immunity can also be achieved against toxins that have
been treated with chemicals so that their toxic nature has
been destroyed even though their antigens for causing
immunity are still intact
• A person can be vaccinated by injection with live
organisms that have been “attenuated”
• Grown in special culture media or have been passed through a
series of animals until they have been mutated enough that they
will not cause disease but do still carry the specific antigens
ALLERGY
• ALLERGY THAT OCCURS IN NORMAL PEOPLE: DELAYED -REACTION
ALLERGY
• Causes skin eruptions in response to certain drugs or chemicals (cosmetics
and household chemicals, to which the skin is often exposed)
• Caused by activated T cells
• Upon repeated exposure it causes the formation of activated helper and
cytotoxic T cells
• Elicits a cell-mediated immunity
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• Examples of Autoimmune diseases:
• Rheumatic fever: Bone becomes immunized against tissues
in the joints and heart, especially the heart valves,
following exposure to a specific type of streptococcal toxin
• Glomerulonephritis: person becomes immunized against
the basement membranes of glomeruli
• Myasthenia gravis: immunity develops against the
acetylcholine receptor proteins of NMJ causing paralysis
• Lupus erythematosus: person becomes immunized against
many different body tissues at the same time
Passive Immunity
• Transfusion of antibodies or lymphocytes to confer
immunity
• ALLERGIES IN THE “ALLERGIC” PERSON
• Atopic Allergy
• Caused by non-ordinary response of the immune system
• Genetically passed on from parent to child
• Presence of large IgE antibodies (reagins or sensitizing
antibodies)
• Allergen: antigen that reacts specifically with a specific type
of IgE reagin antibody
• IgE attaches to mast cells and basophils
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• Substances released: • ANAPHYLAXIS

• Histamine • Widespread allergic reaction throughout the vascular
• Slow-reacting substance of anaphylaxis system and in closely associated tissues
• Eosinophil chemotactic substance • Histamine: causes widespread peripheral vasodilation as
• Heparin well as increased permeability of the capillaries and
• Protease marked loss of plasma from the circulation
• Neutrophil chemotactic substance • Patients dies of circulatory shock within a few minutes
• Platelet activating factors
• Slow-reacting substance: causes spasm of the smooth
• These substances causes: muscle of the bronchioles, eliciting an asthma-like attack
• Dilation of local blood vessels and sometimes causing death by suffocation
• Attraction of eosinophils and neutrophils
• Damage to the local tissues by protease
• Increased permeability of the capillaries
• Loss of fluid into the tissues
• Contraction of local smooth muscle cells

• URTICARIA • HAY FEVER (Allergic Rhinitis)

• Results from antigen entering specific skin areas and
causing localized anaphylactoid reactions
• Histamine causes:
• Vasodilation  red flare
• Increased local permeability of the capillaries that leads to local
circumscribed areas of swelling of the skin (hives)
• ASTHMA
• Allergen-reagin reaction occurs in the nose
• Histamine causes local vascular dilatation with increased
capillary pressure, and increased capillary permeability
• Causes rapid fluid leakage into the tissues of the nose  swelling
of the nasal linings with increased secretions
• Occurs in the bronchioles of the lungs
• Releases slow-reacting substance of anaphylaxis causing
spasm of the bronchial smooth muscle
• Person has difficulty in breathing

BLOOD GROUPS; TRANSFUSION; TISSUE AND ORGAN

TRANSPLANTATION
O-A-B BLOOD GROUPS
BLOOD GROUPS; TRANSFUSION; • THE A AND B ANTIGENS – AGGLUTINOGENS
• Type A and type B occurs on the surfaces of the RBCs in a large
TISSUE AND ORGAN proportion of the population
• Strong antibodies that react specifically with either the type A or
TRANSPLANTATION type B antigen
• Antibodies bind with the red cell antigens to cause agglutination
of the red cells
• Type A and B antigens  Agglutinogens
• Plasma antibodies  Agglutinins

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The 4 Major O-A-B Blood types

• No antigen A and B = Type O (47%)
• (+) A agglutinogen = Type A (41%)
• (+) B agglutinogen = Type B (9%)
• Both A and B agglutinogen = Type AB (3%)

BLOOD TYPE AGGLUTINOGENS AGGLUTININS

O none Anti A and anti-B
A A Anti-B
B B Anti-A
AB A and B none

The Agglutination Process in Transfusion

Reactions Rh BLOOD TYPES
• Major difference between O-A-B system and Rh
• When blood are mismatched, the red cells agglutinate system is the following:
by the following processes: • O-A-B system: The agglutinins responsible for causing
• Agglutinins attach themselves to the RBCs transfusion reaction develop spontaneously
• A single agglutinin can attach to 2 or more different RBCs at the • Rh system: Spontaneous agglutinins almost never occur
same time • Person must first be massively exposed to an Rh antigen before
• Causing the cells to clump enough agglutinins to cause a significant transfusion reaction will
develop
• Clumps plug the small blood vessels
• WBCs and reticuloendothelial system destroys the agglutinated
cells, releasing hgb into the plasma
• Hemolysis of red cells
• Antibodies cause lysis of the RBCs by activating the complement
system which releases proteolytic enzymes that rupture the cell
membranes

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“Rh Positive” and “Rh Negative” Persons • Whites:

• Rh (+): 85%
• Rh (-): 15%
• 6 Common types of Rh antigens, each of which is called Rh factor
• American Blacks:
• C, D, E, c, d, e • Rh (+) 95%
• Type D antigen is widely prevalent in the population • African Blacks:
• More antigenic than the other Rh antigens • Rh (+) 100%
• (+) D antigen = Rh +
• (-) D antigen = Rh-
• Other Rh antigens can still cause transfusion reactions, though usually milder

• EFFECT OF THE MOTHER’S ANTIBODIES ON THE FETUS

ERYTHROBLASTOSIS FETALIS
• Characterized by progressive agglutination and subsequent
phagocytosis of RBCs in fetus or newborns
• Mother is Rh (-), Father is Rh (+)
• The baby has inherited the Rh (+) antigen from the father
• Mother has developed anti-Rh agglutinins that diffuse through the
placenta into the fetus to cause RBC agglutination
• Anti-Rh antibodies have formed in the mother, then diffuse
slowly through the placental membrane into the fetus’
blood
• Causing agglutination of the fetus’ blood
• Agglutinated RBCs subsequently hemolyze releasing hgb
into the blood
• Macrophages convert hgb into bilirubin  jaundice of the
skin

• CLINICAL PICTURE OF ERYTHROBLASTOSIS • TREATMENT OF THE ERYTHROBLASTOTIC BABY

• (+) Jaundice • Replace the newborn infant’s blood with Rh negative blood
• Anemic at birth • 400 ml of Rh(-) blood is infused, while baby’s own blood is
being removed (Exchange transfusion)
• Anti-Rh agglutinins from the mother circulates in the baby’s
blood for 1-2 months after birth, destroying more and • Keeps bilirubin low, to prevent kernicterus
more RBCs
• The liver and spleen become enlarged (hepatomegaly and
splenomegaly)
• Very rapid production of cells, in early forms 
erythroblastosis fetalis
• Severe anemia is usually the cause of death
• (+) Survive: mental impairment or damage to the motor
areas of the brain due to kernicterus

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TRANSFUSION REACTIONS RESULTING FROM • ACUTE KIDNEY SHUTDOWN FOLLOWING

MISMATCHED BLOOD TYPES
• A transfusion reaction is to occur in which the RBCs of
the donor blood are agglutinated
• Very rare that the transfused blood causes
agglutination of the recipients cells for the following
reasons;
• The plasma portion of the donor blood becomes diluted by
the plasma of the recipient
• On the other hand, the infused blood does not dilute
the agglutinins in the recipient’s plasma to a major
extent
• Therefore, the recipient’s agglutinins can still agglutinate
the donor cells
TRANSFUSION REACTIONS
• Begins within a few minutes to a few hours and continue
until the person dies of renal failure
• Causes:
• Antigen-antibody reaction releases toxic substances causing renal
vasoconstriction
• Loss of circulating red cells along with production of toxic
substances from the hemolyzed cells and from the immune
reaction often causes circulatory shock
• Very low BP, decreased renal blood flow and urine output
• Total amount of free hemoglobin in the circulating blood, causing
it to precipitate and block many kidney tubules

TRANSPLANTATION OF TISSUES AND ORGANS

• ISOGRAFT: From 1 identical twin to another
• ALLOGRAFT: Transplant from 1 human being to another or from any
animal to another animal of the same specie
• XENOGRAFT: transplant from a lower animal to a human being or
from an animal of one species to one another species

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