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134 Cards in this Set

  • Front
  • Back
Function of Red Blood Cells
Transport of Hemoglobin
and along with it, oxygen
Contain carbonic anhydrase – which
catalyses CO2 and H2O to form H2CO3
Hb is a good acid-base buffer –
as is any protein
40 women
~34 gm/100 ml red cells
15-16 (male) gm Hb/100 ml blood
13-14 (female) gm Hb/100 ml blood
Oxygen carrying capacity:
gm Hg/100 ml blood * 1.34 ml O2/gm Hb
~21 ml O2/ 100 ml blood for men
~19 ml O2/ 100 ml blood for women
Normal Values
WBC count x 103 ~7.8 ± 3
RBC count x 106 ~5.4 male/mm3
(higher at altitude) x 106 ~4.8 female/mm3
Hemoglobin 16 gm Hb/100ml cells - male
14 “ “ female
hematocrit 47 ± 5 male
42 ± 5 female
RBC indices
MCV ~90 cubic microns
MCH 32 gm/10ml of cells

Platelet count x 103 140-440
Regulation of Red Cell Mass
Balance between production and destruction
~ 1% produced/day ~ 1% destroyed/day
Produced in bone marrow
sternum, pelvis, vertebrae, ribs in adults (flat bones)
Production regulated by erythropoietin
Sites Of Hemopoietic Activity
RBC production
Total RBC mass in circulation must:
1. supply an adequate # of cells to provide O2
2. control the # of cells so as not to impede flow
Erythropoietin is released from kidney in response to low renal oxygenation. (it’s a glycoprotein)

Stimulates stem cells to form pronormoblasts

Promotes release of reticulocytes

Red cell production increases within 24 hours

Erythropoietin life span is 4-12 hours

Increase in red cell number in 5 days

Folic acid and B12 are essential for the maturation of RBCs. Failure to absorb B12 is pernicious anemia. (intrinsic factor from the gastric glands of the stomach wall binds B12, protects it from acidic denaturation in the stomach and allows its absorption through the gut wall). No stomach wall, no B12 absorption.
Biconcave discs
~7.7 um in diameter
Cell membrane is a bag that can deform and resume its original shape
Excess of cell membrane relative to its contents, the membrane doesn’t stretch much when the cell distorts and therefore doesn’t rupture as easily as any other cell would.
Any drop in tissue O2 levels will cause an increase in RBC production,
if EPO is present in circulation

90% EPO produced in peritubular interstitial cells of the kidney

Also produced in the liver ~10%

No preformed stores of erythropoietin

High hematocrit suppresses erythropoietin production
but does not abolish it

Erythropoietin is always present in the plasma

In individuals with damaged or removed kidneys,
EPO drops and anemia increases
Hb formation begins in the proerythroblasts
Subunit Hb chains are alpha, beta, gamma, and delta – each has a slightly different a.a. sequence
In adults, Hb has two alphas and two betas, each on associated with a heme group.
Each heme binds one molecule of O2 loosely
Different types of Hb have different affinities for O2.
Sickle cell has an a.a. mis-read in the beta chains and exposed to low O2, it forms crystals – distorting shape, affecting circulation, causing hemolysis and anemia

Our hbg is 2 alphas and 2 beta

Sicke cell helps fight malaria, but not the other way around.
Destruction of Red Blood Cells
< 100 days survival hemolysis
Decrease in enzyme activity, ATP levels, and MCH
Decreased deformability (spherocytosis)
Binding by IgG
Ingested by macrophage in spleen
extravascular hemolysis
Iron release to transferrin
Hemoglobin excreted as bilirubin

120 day life

The iron gets recycled to transferrin…then reused or excreted can be stored by hemociterin
Iron Metabolism
Fe important for Hb, myoglobin, cytochrome, several oxidative enzymes
7 mg/1000 calories ~ 10% absorbed, 1-1.5 mg/day
absorption enhanced by meat, poultry, fish
inhibited by carbonates, tannate (tea), oxalate (spinach, rhubarb), phosphates (vegetables), clay
duodenum and upper jejunum major site absorption
HCl promotes absorption
loss 1 mg/day males average
menstruating women additional 14 mg/period loss

Odd turds d/t weird bilirubin, biliverdin
Iron Transport and Storage
Transferrin in plasma
Two iron binding sites
Responsible for pink color of plasma
1/3 of sites are occupied, TIBC = 300 ug/ml, 30% saturation, 100 ug/ml
Ferritin in cellular cytoplasm
30% of total iron
Hemosiderin collects in cells
Water insoluble
Blood loss anemia – Hct is normal
Aplastic anemia – bone marrow failure – no cells
Megaloblastic anemia – deficiency of B12, folate or intrinsic factor – cells grow too big and don’t function well
Hemolytic anemia – fragile RBCs, sickle cell, Rh response in pregnancy, some microorganisms, rough sample handling

Anemia is failure of blood to carry oxygen
Reticulocyte Index
Retic = relative percent of cells that are reticulocytes
Need to correct to get absolute percentage

RI= Retic (%) * Hc(patients)/Hc (normal)
Bone marrow failure, renal disease, hemolytic anemia
macrocytic, normochromic
microcytic, hypochromic
iron deficiency, chronmic disease

Aplastic anemia
Drugs - chemotherapy, antibiotics, antidepressants, ethanol
Chemicals - benzene
Immune suppression of stem cell
Malignancy (non-hematopoietic tumors and transformation of hematopoietic stem cells)

Aplastic Anemia decrease in all cells RBC, WBC ,platelets
Primary is idiopathic 40-70~ of total

Reduced erythropoietin response
Acute inflammatory state
acute, chronic bacterial infections
Renal Disease
Hypometabolic state
protein deprivation
endocrine deficiency
Maturation defects
South European, African, Asian
defect in hemoglobin synthesis
microcytic, hypochromic
transfusions, folic acid
Megaloblastic Anemias
Large fragile red blood cells
Impaired DNA synthesis
Increased utilization
Folic Acid Deficiency
Inadequate diet, Dialysis, cirrhosis, vegetarian
Impaired absorption
Folate very heat labile
Vitamin B12 Deficiency
Inadequate diet
Impaired absorption
Intrinsic factor (glycoprotein secreted by gastic parietal cells)
(Pernicious anemia)

Increased MCV increased MCH
Folate and B12 are required for DNA synthesis
Folic acid green leafy vegetables, dairy products 3-6 months stored
B12 diet not a problem 3-6 years
B12 not in fruits and vegetables
Absorbed in ileum after binds to intrinsic factor
Prenicious anemia (lack intrinsic factor)
mucosal damage, endocrine, immune, partial excision of stomach.
Hemolytic, Blood Loss
Sickle cell (hemoglobin)
Spherocytosis (membrane)
Microangiopathic hemolytic anemia
Immune responses, mismatch typing

Sickle cell become ridig, rupture
spherocytosis membrane defect that decreased lipid content, impaired flexibility
2o Caused by tissue hypoxia – whatever the reason – up to 30% h in RBCs
Vera – blasts don’t respond to high RBC levels and continue making all formed elements
Three Pathophysiological Categories of Polycythemia
Relative Polycythemia (Red Blood Cell Mass Normal, Plasma Volume Decreased)
Secondary Polycythemia (Red Blood Cell Mass Increased)
Polycythemia vera (Red Blood Cell Mass Increased)
Mechanical & chemical resistance of the body to infection
Gut---Mucous, acid, normal gut flora and fast transit time

Lung--ciliary elevator

Also – intact, acidic, dry surface skin
Leukocytes / White Blood Cells
Granulocytes (65%)
neutrophils, eosinophils, basophils
formed in bone marrow
Monocytes (5%)
tissue macrophages
formed in bone marrow
Lymphocytes (30%)
formed in lymph tissue
Leukocytes Classification
Granulocytes Non- Granulocytes
Neutrophils - Monocytes
Eosinophils - Lymphocytes
Polymorphonuclear Mononuclear
Neutrophils - Monocytes
Eosinophils - Lymphocytes
Phagocytes Non-phagocytes
Neutrophils, monocytes - Lymphocytes
Macrophages, eosinophils - Basophils
Phagocytic Cells
Polymorphonuclear Neutrophils
non-dividing, short-lived
dominant number in bloodstream
long-lived cells
do not circulate
present in tissue, particularly in lungs,
spleen, liver, lymph nodes
tissue macrophage system

Neutrophils 9-10 days

5-7 days in maturation and storage, 2-3 days in bone marrow
~ 2% of total white blood cells
active against parasites, skin diseases, chronic infections
phagocytic and immunomodulatory, decrease inflammation
– long term
~ 0.5% of total white blood cells
basophils similar to mast cells
release primarily histamine, some bradykinin
release due to binding of IgE
Monocyte-Macrophage System
Monos and Macs phagocytize: large quantities of bacteria, viruses, necrotic tissue, and any foreign particle
Monocytes precursors of osteoclasts
Atherosclerosis (foam cells are macrophages)
Responsible for fever - along with other molecules
Tissue macrophages
macrophages of lymph system
alveolar macrophages
Kupffer cells in the liver
macrophages of the spleen and bone marrow

Monocytes formed from same cells as neutrophils
liver phagocytic cells?
phagocytic cells only in blood
Actions of Phagocytic Cells (which live weeks to months, in and out of circulation)
1. Margination
2. Diapedesis
3. Ameboid Motion
4. Chemotaxis
5. Phagocytosis
Antigenic microbe activates binding molecules on the endothelial wall of the cap. Allowing for margination, diapedesis, and chemotaxis
Antigen-any protein anywhere--generates and antibody response (implies it’s not a native protien

The markers on cells are called Major Histocompatiboility Comple (MHC)

All of your cells are genetically marked cells-1.2 from mom and 1/2 from dad. Up to about 14 months you can add protiens and they become ‘yours’ after that, it’s a no go

340-360 different one in humans-possible there fore there are billions of possible combinations. Your cell can recognize your cells…..and the fact that other cells are not yours.

HLA- human leukocyte antigens can ‘flash a badge that say’s I’m OK’ These are MHC’s that apple to white cells.
Neutrophilic (or macropage) response to antigen- first line of defense
ER makes lysosomes

Neutrophils ingest, macros grab hold and squirt--affects cell neighborhood. neutros have a grater change of being killed offf.
An antigen is a
protien that can induce
an immune response when introduced into
an immunocompetent host and that can react
with the antibody produced from that response


Most antigens have variety of antigenic determinants
Agglutination process needed to remove antigens from circulation
Must have both antibdy and atigen for agglutyination
adaptive (specific immunity)
involved B cell stimulation to produce specific antibodies
first neutrophill, then monocytes, thenm t-lunpohocytes

[troop surge]
Monocytes become macrophages

T’s and b’s

T’s don’t make antibodies
B’s make them
B-lympho.s stimulated to become plasma cells and memory cells
Plasma and memory cells are still B’s

Parts of the B clone become memory cells and don’t produce antibody, but maintain the genes that are effective against that group of antigen.
The rest of the B clone become plasma cells and produce specific effective, antibody
One pathogen has many different surface antigens – each of which can stimulate different B-cell responses
Complement attatchment-will be destroyed.
Serum electrophoresis. A=albumin, and the others in order of size and charge. Immunoglobulins are all gamma
Our immunologic antibodies/antigens are gammaglobulin,
main form of antibodies in circulation
productin increased after i mmunizatin,
secreted during secondary response
main antibody in external secretions
saliva, mother's mimlk
responsibloe for allergy sx in allergic reactions, hypersenstivity
function as antigen receptors on lymphocyute surface prior to immunization.

secreteed during primary response
Function as antigen recptors on lypmphocyte surface prior to immunization.

other functions unknown
Memory B Cells--- stronger antigen binding
Memory T-cells--- production of cytokines

Tolerance to self-antigens
1) do not generate receptors to self antigens
2) learn not to respond to self antigens ******
kill self-reacive lymphocytes
inactivate lymphocytes

Tolerance to self antigen someties breaks down
Autoimmune diseases
antigen B is product of secondary response (40-45 days)
Complement System
Series of ~ 20 proteins
Activated by microorganisms
Will coat the microorganisms

Adherence reactions
phagocytic cells have receptors for C3
Biological active fragments
produce reactive oxygen intermediates
Membrane lesions
Activate mast cells

Inactivated---specific inhibitory proteins

if complement doesn’t bind quickly then ecome inactivated

Complement marks antigen for explosion and is ever present in the plasma
Antibody attaches to bad guy. Complement (a protein) attaches to antibody. C4 complement splits and attaches to bad guy membrane. Other “C” operatives rendezvous at C4 and set up a pore (cell explosive device) on the perimeter boundary of the target. Cell lysis by influx of surrounding water. The whole process is “opsonization’.
Porforins-they bore a pore in the cell membrane
fucntions of complement activation?
1. lysis
2. chemotaxix
3. opsonization
An antigen will stimulate both B & T cell production, and the presence of Ts further stimulates Bs specific for more antigens on the bad guy surface
Killer T’s are destryed by HIV. (all t’s are susceptible to HIV)

bacterial infection=granulocyte response

Lymphos are more viral
Crude amount of exposure will determine if the infection is clinical or sub-clinical, or fatal, along with the magnitude of the immune response
With vaccination, we try to present the attenuated (slowed down) version.

The vaccine gets rid of the DNA, but retains the outer structure, per se. The antigen cannot replicate.

The release of IG’s after a vaccination cause the HA, etc ……
B cells are made in burst cells (bone)
humoral immunity (secretes antibodies)
memory cells, plasma cells
receptors present
low in blood
10-15% of lyphocytes
transfromed to plasma cells
secretes antibodies
T’s programmed in Thymus
cell mediated immunity
cytotoxic, helper cells
no surface antibodies
long life spam
lots in blood and lymph
transfromed to activated lymphocytes
secretes lymphokines
Antigen presenting dendritic cells carry antigen to lymphoid organs for the programming of T cells
Interaction between helper Ts, Bs and antigen presenting dendritic cells
Act over a short range

Interact with another cell in body
Can kill or signal other cell

Only recognize antigen when presented
on surface of target cell

Interleukin is very effective against viruses……in prostaglandin case

Cytotoxic Cells
kill infected cells

Helper Cells (two types)
activate macrophages and B-cells

Suppressor Cells
regulate activity
present foreign peptides to cytotoxic cells

present foreign peptides to helper cells

MHC-I on all cells because cytotoxic cells must act against all cells

MHC-II on B cells, macrophages, dendritic, and antigen presenting cells.

Have CD4 and CD8 to help binding

CD4 helper bind MHC-II
CD8 cytotoxic cell bind MHC-I

CD8 on cytotoxic t cells
CD4 on helper cells

Cytotoxic cell recognize viral particles
Infected cells are all nucleated cells
antigen presenting cells are B-Cells and macrophages
Cytotoxic cells focus attack on cells that make foreign antigens (menace)
helper t-cells focue help on cells that take up foreign antigens (essential for immune response)
Helper T-cells
Helper T-Cells stimulate macrophages and B-cells
Helper T-Cells recognize foreign antigen bound to
MHC-II proteins on surface of antigen-presenting cells
Two signals are required for activation of Helper T-Cells
Cytotoxic T-cells
Pore forming protein
Cytotoxic T-Cells recognize viral protein fragments on
surface of infected cells.

Cytotoxic T-Cells induce infected cells to kill themselves
Bind to infected cells
Induce cell death
Punch holes in cell membrane
Natural Killer
destroy virus-infected cells
do not express antigen specific receptors
cells with low levels of MHC I
induce cells to undergo apoptosis
Make interleukins
Helper Ts


Interleuikin in a product of helper T’s
1. Vasodilation
2. Increased capillary permeability
3. Clotting of interstitial fluid
4. Swelling of tissue
5. Pain
Substances involved
bradykinin, histamine, serotonin,
complement, coagulation factors, lymphokines-
interleukins from Helper Ts
“Walling off” effect of inflammation

5 cardinal signs of inflammation

Cell-mediated Response to Inflammation
1. Tissue macrophages
already present in tissue
2. Neutrophil invasion
margination, diapedesis, chemotaxis
stimulation of bone marrow to release stored leukocytes, 4-5 hours
3. Macrophage proliferation
invasion by circulating monocytes (several hours to increase size)
4. Stimulation of granulocyte and monocyte production
growth factors produced by tissue macrophages:
Granulocyte colony stimulating factor GCSF
Interleukins IL (several flavors)
Monocyte colony stimulating factor MCSF
Tumor necrosis factor TNF
and many more….
Neutropenia: decreased number of neutrophils
Decreased production
Increased neutrophil destruction (chronic infections)

Agranulocytosis: severe neutropenia due to production failure
due to irradiation, exposure to chemicals, drugs,
bone marrow failure

Decrease production
inherited stem cell disorders
chemical toxicity

Increased destruction
immune mechanisms
Killer T contacting a cancer cell. It looks for specific cancer cell antigens on the cell surface and….
Releases lymphokines that destroy the cancer cell
Hypersensitivity to some antigenic protein
Immediate hyper – abnormal B response – releases high levels of IgE
Allergic rhinitis, conjunctivitis, asthma, dermatitis, urticaria, hives.
Immediate and treated with antihistamines
Delayed – abnormal T cell response
Hours to days
Treat with cortisone
IgE and Histamine Release
IgE binds to mast cells release histamine and other agents which activae eosinophils.

Histamine help increase premeability,
activation of complement
allergic reaction
first B, IgE,

then T and cell mediated
autoimmune diseases

sympathetic opthalmia
autoimmune diseases
autoimmune diseases
TSH receptor protiens
autoimmune diseases
thrombocytopenici purpura
I, rH and other on RBC surface
autoimmune diseases
myesthenia Gravis
ACH receptors
autoimmune diseases

rhematic fever
autoimmune diseases

autoimmune diseases

autoimmune diseases

DNA, RNA, nucleprotien
autoimmune diseases
DM -1
beta cells-pancreatic islet
autoimmune diseases

myelin shealth components
Reverse transcriber-go make DNA

More Americans have died from AIDS than died in both World Wars
40 million world wide are infected
Aids has a latency period of ~ 8 years
Intracellular – so most immune response mechanisms don’t work
Virus is specific for killing WBCs particularly T cells
Drugs that are effective block reverse transcriptase and block viral particle attachment in the first place
Lymphocytic leukemia – cancerous production of lymphoid cells. In any lymph tissue like nodes or lymphocytic tissue in gut
Myelogenous leukemia – cancerous production of bone marrow stem cells. They circulate anywhere and begin making inappropriate WBCs. Cells usually bizarre and undifferentiated.
Common symptoms of both are: infection, anemia, bleeding disorders. Starves out normal cell growth
Blood Groups
Red blood cell surface antigens: glycolipids or glycoproteins

A-B-O System
antigens: surface antigens (A,B)
genes (A, B, O)
inherited (two surface chromosomes
also present on all cells in the body
antibody in plasma: gamma globulins, anti-A, anti-B, IgM, IgG
geno OO
no atigen
anti-a, anti B antibodies
geno OA or AA
antigen A
anti-b antibody
geno OB or BB
antigen B
anti-a antibody
geno AB
antigen AB
no antibodies
Hemophillia A (factor 8-ahf)
recessive on X
delayed formation of fibrin
von willibrands (factor 8-vwf)
dominant train on autosomal
impaired ability of platelets to adhere to collagen in sunendothelial connective tissue
hemophilia B (factor 9)

aka x-mas tree disease
recessive on X

delayed formation of fibrin
inhibits protaglandin production resulting in a defective platelet release reaction
inactivates vik K
inhibits activity of thrombin
combines with ca++ and thus inhibits the activity of many clotting factors
Rhesus System
antigens on RBCs: 6 rhesus factors (C, D, E, c, d, e)
inherited as triplets
CDE, CDe, Cde, CdE, cDE, cDe, cde
antigen D =Rhesus positive

antibody in plasma: do not occur spontaneously, only after
exposure to Rh antigens

Rh+ blood into Rh negative person:
sensitization to further Rh+ transfusion

If severe transfusions from 26th wek to delivery
Prevention administer anti Rh antibodies immediately after delivery, amniocentesis
Hemolytic Disease of the Newborn or
Erythroblastosis fetalis
Fetal blood enters maternal circulation

Rh positive fetus and a Rh negative mother
Anti-D antigens form in mother
More critical with 2nd Rh positive child
Treatment- injection of IgG anti-D into
mother after delivery to
destroy fetal RBCs in mom
O mother and A or B fetus
IgG anti-A and anti-B cross placenta
very mild effects
Transfusion Reaction
Transfusion reaction due to agglutination of donor blood

Agglutination of red blood cells due to antigen-antibody reaction
Activation of complement system

Agglutination destroyed by white cells, with hemoglobin
released into plasma

Shock, chills, fever, shortness of breath, renal shutdown

Activation of complement
ABO activation is immediate

Delayed due to Rh
HLA System ----- surface antigens >100
on all nucleated cells

Rejection ---- mainly due to activation of T-cells

Suppressive therapy---- inhibit immune response

glucocorticoids-- limits movement of granulocytes into tissue
and suppresses lymphoid tissue growth
azathioprine - inhibits the functioning lymphocytes – toxic to lymph tissue
cyclosporine --- inhibits T-cell formation
Hemostasis, Coagulation
1. Vascular Spasm

2. Platelet plug

3. Formation of clot
Formed in bone marrow, 150-350,000 /µl
Sequestered in spleen (30%)
2-4 μm in diameter, life span 8-12 days, no nucleus

Active cytoplasm
adhere to collagen in damaged tissue
actin + myosin – able to contract
enzyme synthesis + storage of calcium
synthesis & release of prostaglandins (Thromboxane A2)
dense granules containing ADP and ATP
α-granules (fibrinogen, PDGF, vWF, fibronectin)
fibrin stabilizing factor
Activators of platelets
Collagen and microfibrillar proteins
ADP released from damaged RBCs and activated platelets
Thromboxane from activated platelets
Platelet activating factor from basophils
Epinephrine (stress)
Vessel injury or atherosclerotic plaque rupture
subendothelial protein layer exposed
platelets bind to subendothelial vWF, and collagen via
surface glycoproteins.
platelets swell
release platelet agonists from granules
generate thrombin
activation of new platelets
crosslinking of platelet aggregate by surface glycoprotein
contractile elements pull fibrin threads
Leukotrienes (chemoattractants)
Thromboxane (release more granules)
Release of thrombospondin (stabilizes platelet-fibrin)
Release of PDGF (stimulates smooth muscle proliferation)
(platelet dependant growth factor)
Release of ADP (attracts more platelets)
All cells produce prostaglandins
Leukotrienes and prostaglandins are autocrine regulators
PGE2 – vasodilation – redness and swelling of inflammation
PGF2alpha – bronchiolar constriction
TXA2 – produced by platelets – vasoconstriction and platelet aggregation
PGI2 (prostacyclin) - produced by endothelial cells- inhibit aggregation and vasodilates vessels
Promote most aspects of the inflammatory process – including pain and fever
Big role in repro – ovulation, corpus luteum formation, labor, cramps, bloating..
Produced by stomach and intestinal walls where they inhibit secretion of HCl. High aspirin = peptic ulcers
Opposing prostaglandins in bronchiolar smooth MM response
Opposing Prostaglandins in circ. System
PGE2 causes ductus arteriosus to remain open in the fetus.
Prostaglandins in/ from the kidneys cause increased renal blood flow and increased excretiion of water & electrolytes
Extrinsic Pathway
Damaged vascular wall
Release of tissue thromboplastin – Factor III (it’s mostly phospholipids from the damaged cell membrane)
VII, X and Ca++
V and Ca++
Prothrombin is II
Fibrinogen is I
Ca++ is IV
Intrinsic Pathway
Blood cells damaged or in contact with an unusual surface
XII and damaged platelets
XI and IX
IX, VII, and phospholipids activates X
X, V and down through the common pathway
converted to fibrin
converted to thrombin
tissue thromboplastin
Ca ions
no longer referenced

the same as 5
antihemophillic factor
plasma thromboplastin component (xmass tree factor)
stuart-power factor
plasma thromboplastin antecedent
hageman factor
fibrin stabilizing factor
Polymerization catalyzed by Factor XIIIa
XIIIa crosslinks fibronectin
Fibronectin promotes in growth fibroblasts
XIIIa crosslinks a2-antiplasmin
a2-antiplasmin protects from plasmin

Clots dissolove because plasmin (digests the fibrin in clots)
Conversion of prothrombin into thrombin
prothrombin (factor II) --- formed in the liver
and requires Vitamin K
Split in two thrombin --- proteolytic enzyme
a) acts on fibrinogen b) stimulates fibrin stabilizing factor
c) acts on prothrombin + clotting factors (positive feedback)
Conversion of fibrinogen into fibrin threads
fibrin is split into fibrin monomers
b) automatic polymerization into long fibrin threads (weak)
c.) fibrin stabilization (strong bonds requires Factor XIII)
Formation of Prothrombin Activator
I. Extrinsic pathway
tissue trauma tissue thromboplastin (+VII) X activation
Rapid and explosive in nature (15 seconds)

II. Intrinsic pathway
blood cell trauma, contact with collagen or activated platelets
XII XI IX (+VIII) X activation
slower (2-6 minutes) many components (cascade)

Common pathway
Xa combined with V and platelet phospholipids (PF3) + Ca++
prothrombin activator: prothrombin thrombin fibrinogen
Intravascular Anticoagulants
I. Endothelial Cells – negatively charged
smooth surface + glycocalyx
II. Antithrombin action of FIBRIN (absorbs thrombin)
and keeps the clot local
III. Antithrombin III (alpha-globulin, combines with heparin)
in circulation. Antithrombin deactivates thrombin
IV. Heparin: conjugated polysaccharide, negative charge
little action unless combined with antithrombin III
Increases effect of antithrombin
Fibrinolytic System
Plasminogen = circulating globulin
Plasmin = proteolytic enzyme, similar to trypsin
digest fibrin threads, fibrinogen, and other clotting factors Significance: removal of tiny little clots
Plasminogen activators:
Tissue Plasminogen Activator (TPA), urokinase, streptokinase
released from damaged tissue after a few days
converts plasminogen into plasmin after the clot has resolved
begins to break down fibrin
Coagulation Defects
I. Vitamin C deficiency
lack of stable collagen (elderly, alcoholics)
II. Hepatic failure
almost all clotting factors are made in the liver
III. Vitamin K deficiency
required for II (prothrombin), VII, IX, and X production
fat malabsorption - and along with it, fat soluble Vit. K
IV. Hemophilia
Factor VIII (hemophilia A 1/10,000), 85% of cases
Factor IX (hemophilia B 1/100,000)
chromosome X
V. Thrombocytopenia – lack of platelets usu. below 50,000/ul
bleeding small capillaries and blood vessels
mucosal, skin
low number of platelets
ITP- autoimmune (common) - idiopathic thrombocytopenia
VI. Disseminated Intravascular Clotting - DIC
abnormal bleeding and clot formation
critically ill patients
coagulation and clot lysis in uncontrolled manner
due to massive tissue damage &
depletion of clotting factors
Defective Coagulation
Thromboembolic conditions
clots from: 1. roughened vasc surfaces or
2. slow moving blood - stasis
venous thrombosis, pulmonary embolism (rt)
clots in the arts (lft) to brain, kidneys
artificial heart valves, by-pass surgery
long-term bed immobilization
Treatment for coag
HEPARIN — immediate anticoagulation
Lasts 1.5 – 4 hours

COUMARINS — compete with Vitamin K, 2-4 days to act
Blocks formation of VII, IX and X
reverse with Vitamin K
Collection tube anticoagulation
HEPARIN - promotes anti thrombin in the blood
used in hemodialysis
heart-lung machine
“bind” calcium which is required for clotting
oxalates - chelate Ca++ out of blood
citrates – deionize Ca++ - so it no longer works in the cascade
Blood Coagulation Tests
Platelet count
150,000-300,000/ µl is normal
thrombocytopenia - aplastic anemia, autoimmune
platelet function - myeloproliferative, uremia,
drugs (aspirin, antibiotics), von Willebrand Disease
Bleeding Time
time for skin wound to stop bleeding