Transcript Ch 19 Student_CirBloodx

Chapter 19
The Blood
18-1
Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Introduction
Human body – a multicellular structure
• All cells must have nutrients and eliminate waste products
• Body fluids help in connecting cells
– Intracellular fluid: cytoplasm
– Extracellular fluid: interstitial fluid, blood plasma, lymph, CSF
• Two major networks connect cells:
– Circulatory system (cardiovascular)
– Lymphatic system
Circulatory system (cardiovascular)
• Consists of the heart, blood vessels and blood
– Cardiovascular system heart and blood vessels only
• Hematology – the study of blood
• Functions of circulatory system
– Transport- O2, CO2, nutrients, wastes, hormones, and stem cells
– Protection- inflammation, spread of infection, destroy
microorganisms and cancer cells, neutralize toxins, and initiates
clotting to prevent blood loss
– Regulation - fluid balance, stabilizes pH of ECF, produces ion
balance (Ca+, K+, Na+) and temperature control, absorbs and
neutralizes acids (ie: lactic acid)
Blood
Blood is a liquid connective tissue consisting of cells and extracellular
matrix (whole blood)
• Plasma – matrix of blood (55%)
– a clear, light yellow fluid
• Suspended formed elements – blood cells (red and white) / cell
fragments (platelets) (45%). Termed formed because they are
enclosed in a membrane, visible with microscope, have definite
structure
• Volume in average human body: 4-6 liters
- males 5-6 liters 1.5 gallons [testosterone increases production]
- females 4-5 liters 1.2 gallons
- Viscosity: 4.5 – 5.5 - resistance of a fluid to flow
- Water has a viscosity of 1- blood has 4.5 - 5.5x greater “thickness”
than water; 5x “stickier”, 5x more cohesive
- Higher the viscosity ; slower the flow – greater resistance to flow
- Temperature: 38°C or 100.4°F
- pH: 7.35 – 7.4 slightly basic
- Osmotic concentration: the measure of solute concentration;
dissolved particles that cannot pass through the blood vessel wall
- Too high = elevated BP
Too low= decreased BP, edema
> holds excess fluid
> less solutes to maintain fluid levels
Withdrawing Blood
– Venipuncture: from a vein
• closer to surface, thinner walls,
lower BP, smoother flow
– Finger-stick: from a fingertip,
ear lobe, heel
• small amount required
– Arterial stick: from an artery
• for monitoring oxygenation
• High pressure
• Radial (wrist) or brachial arteries
(elbow)
• Needle phobia is a defined
medical condition that affects
between 20 - 23 % of the
population to such an extent that it
may cause them to avoid needed
medical care.
Bevel edge creates
a sharp pointed tip
allowing the needle
to easily penetrate
the skin
18-4
Components and Properties of Blood
• 7 kinds of formed elements
– erythrocytes - red blood
cells (RBCs)
• Ratio: 1000 RBCs to
every 1 WBC
– platelets
• cell fragments from
special cell in bone
marrow
– leukocytes - white blood cells (WBCs)
• 5 leukocyte types divided into 2 categories:
• granulocytes (with granules- contain enzymes)
– neutrophils, eosinophils, basophils
• agranulocytes (without granules)
– lymphocytes, monocytes
18-5
Formed Elements of Blood
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Monocyte
Small
lymphocyte
Neutrophil
Platelets
Eosinophil
Small
lymphocyte
Erythrocyte
Young (band)
neutrophil
Neutrophil
Monocyte
Large
lymphocyte
Neutrophil
Basophil
18-6
Separating Plasma From Formed Elements
CENTRIFUGE
separates plasma
from formed
elements
HEMATOCRIT - % of blood volume
comprised of RED BLOOD CELLS
(RBC)
• erythrocytes are heaviest; settle first
– 37% to 52% of total volume
– Males: 40-54 – androgens stimulate
higher RBC production
– Females: 37-47
• white blood cells and platelets
– 1% total volume
– buffy coat
• plasma
– 47% - 63% of total volume
– complex mixture of water, proteins,
nutrients (fatty acids, amino acids,
glucose, iron, cholesterol, vitamins),
electrolytes, nitrogenous wastes
(urea), hormones, and gases
Plasma and Plasma Proteins
> Plasma – (47%-63% of blood volume) liquid portion of blood; Consists of
92% water; difference between plasma and surrounding interstitial fluid is
the level of gases and the types and concentration of some blood proteins.
5xs MORE PROTEIN in plasma than interstitial fluid
– serum – identical to plasma except for the absence of fibrinogen
> Plasma proteins account for 7% of plasma; 90% formed in the liver
1. ALBUMINS – smallest and most abundant (60%)
• contributes to viscosity / osmolarity, affects BP, flow and fluid balance
• Transport H2O-insoluble substances – fats, hormones [testosterone,
cortisol, T3, T4]
2. GLOBULINS - made by liver and WBC (35%); higher molecular
weight and greater water solubility than albumins
• Gamma (antibodies), complement - immune system functions
• Alpha – transport hemoglobin, ceruloplasmin (enzyme), prothrombin
• Metalloproteins – transport minerals: transferrin-iron
• Lipoprotein transport fats/lipids (chylomicron)
• Hormone-binding: thyroid-binding, transcortin (ACTH)
• Steroid-binding transport water-insoluble sterols (hormones)
3. FIBRINOGEN (4%)
• precursor of fibrin threads that help form blood clots
> Other elements contribute to the remaining 1% = electrolytes, nutrients,
waste products (bilirubin, urea, CO2, ammonia)
Albumin binds to such chemicals as the antibody tetracycline to
transport throughout the body.
https://www.aasv.org/shap/issues/v6n5/v6n5p189f9.jpg
18-9
Hemopoiesis/Hematopoiesis
• The formation of blood, especially its formed elements
• Adult production of 400 BILLION platelets, 200 BILLION RBCs
and 10 BILLION WBCs EVERY DAY!
• Hemopoietic tissues produce blood cells
– In developing embryos, blood formation and the production of
stem cells occurs in the yolk sac. As development progresses,
hemopoeisis also occurs in the spleen, liver, and lymph nodes.
– The liver stops producing blood cells at or soon following birth.
– Maturation, activation, and some proliferation of lymphoid cells
continues in secondary lymphoid organs (spleen, thymus, and
lymph nodes).
– Once bone marrow develops, it forms the majority of the blood
cells.
– red bone marrow in adults limited to the skull, vertebrae, ribs,
sternum, part of pelvic girdle, the proximal heads of the femur
and humerus
– red bone marrow can be found in most all children bones
• Chemotherapy destroys stem cells leading to low blood production;
growth factors generally given following treatment to stimulate cell
synthesis
yolk sac
produces stem
cells for first
blood cells
http://blueridgeobg.com/images/uterus2.jpg
18-11
Hematopoiesis
Hemopoiesis
(Blood Formation)
2 types of pluripotent stem cells (plurimus =very many / potens=having
power). Also called hemocytoblasts or hemopoietic stem cells
• Myeloid stem cells (BONE MARROW)
RBC, platelets, and 4 out of the 5 WBC (eosinophils, basophils,
neutrophils, monocytes)
• Lymphoid stem cells (LYMPHATIC ORGANS)
Remaining WBC (lymphocytes)
Blood formation stimulated by:
• Hormones: (testosterone, erythropoietin-[RBC] and thrombopoietin
[platelets])
• Vitamins B6, B12, folic acid; Minerals – iron
Erythrocytes
1. 99% of the formed elements
2. 4.8 – 5.4 million RBC / cu mm of blood*
3. Biconcave; No nucleus- no protein
synthesis or mitosis
4. Lack mitochondria – produce ATP by
anaerobic respiration (glycolysis) glucose absorbed from plasma
5. Loss of organelles increases surface
area allowing for higher diffusion rate
of gases and other substances
6. Cytoskeletal proteins provide flexibility
and enable cells to stack on top of one
another to squeeze through small
capillaries walls
7. Cytoplasm has red protein –
hemoglobin
8. Plasma membrane has ABO and Rh
antigens/markers- for blood typing
9. Transport gases: most O2 (98.5%);
some CO2 (23%)
* 0.000033814 fluid oz = 1cu/mm
Erythropoiesis: RBC Production
1. 3 million RBCs produced “PER SECOND!!”
2. Average lifespan = 120 days
3. Development takes 3-5 days
4. Pluripotent stem cells give rise to erythrocyte colony forming unit
with receptors for erythropoietin (EPO) HORMONE from kidneys
 EPO stimulates CFU to synthesize erythroblasts
 Erythroblasts stimulate internal synthesis of hemoglobin (Hb)
5. When level of hemoglobin inside “forming RBC” reaches 34%
 nucleus is ejected; an indention forms
 Cell becomes a reticulocyte
• ½ to 1½ % of circulating RBCs are reticulocytes
6. Reticulocytes migrate from bone marrow to enter the blood
 Circulate for 1-2 days and increase their hemoglobin content with
what remains of their ribosomes (“protein factories”)
7. Mature erythrocytes are formed
Contain
receptors for
erythropoietin
EPO stimulates RBC ejects Reticulocytes
most
erythroblasts
migrate to
organelles;
synthesis;
blood; become
now a
Erythroblasts reticulocyte
mature
stimulate
erythrocytes
immature
RBC
hemoglobin
production
18-16
Erythrocytes
HEMOGLOBIN (Hb)
• 280 million/per each RBC [WOW!]
• Hb molecule structure consists of:
– Four (4) polypeptide globins (protein).
– Non-protein pigment molecules – Fe (iron)
attached to each heme
• O2 (98%) binds to Fe of Hb in the lungs 
oxyhemoglobin; insoluble in plasma; binding
capacity with hydrogen in water is weak.
• CO2 (23%) binds to globins of hemoglobin in
the tissues  carbaminohemoglobin; 77% in
plasma; CO2 soluble; strong binding capacity
with hydrogen in water
• Vitamin B12 B6 and folic acid
– Provides rapid cell division and DNA
synthesis to form RBC; stimulate enzymes
that synthesize heme component of
hemoglobin
• Vitamin C and copper - cofactors for
enzymes synthesizing hemoglobin
• Copper transported in blood by alpha
• Infants: 14-20 g/100ml blood
globulin component of the enzyme,
• Adult Females:12-16g/100 ml
ceruloplasmin, that converts iron to a
• Adult Males: 14-18g/100ml
form that will bind with hemoglobin.
IRON
• lost daily through
urine, feces, and
bleeding
• dietary iron: ferric
(Fe3+) and ferrous
(Fe2+)
– stomach acid
converts Fe3+ to
absorbable Fe2+
http://fgamedia.org/faculty/cholcroft/Bio45/Bio45_Images/TraceMineralsUnit/IronAbsTrans.jpg
• Transferrin controls the level of free iron in biological fluids; absorbs
and binds iron in the blood and transports it to bone marrow, liver,
muscles, and other tissues [carries 2 Fe3+ molecules]
• RBCs absorb transferrin and amino acids from bone marrow to
produce hemoglobin
• Excess iron is stored as ferritin and hemosiderin. Iron storage in
hemosiderin is not readily available to cells. Can result in iron
overload = a condition known as hemosiderosis
http://fgamedia.org/faculty/cholcroft/Bio45/Bio45_Images/TraceMineralsUnit/IronAbsTrans.jpg
18-19
Carbon Monoxide Poisoning
CO binds to oxygen sites on
Hb BLOCKING ability
of RBC to transport
O2 to cells.
http://kidneyinthenews.files.wordpress.com/2008/0
3/19443.jpg
http://image1.masterfile.com/em_w/03/34/82/861-03348241w.jpg
18-20
Erythrocytes Conditions
CBC: Complete Blood Count
– Blood sample is tested to determine the number of RBC and all the
types of WBC
Hematocrit: Normal % of RBC in blood
40-54% in males
38-46% in females
Polycethmia: hematocrit > 55%
- Increased RBC count  increased blood viscosity  increased BP
 increased chances of thrombosis and hemorrhage
Hypoxia: oxygen deficiency > 40%
- Due to decreased oxygen in the atmosphere, decreased number of RBC,
lack of blood circulation
Blood doping: Increases RBC count in the blood.
(+) Provides more oxygen to the muscles  better performance.
(–) Increases blood viscosity  increases load on heart
1) injecting previously stored RBC
2) blood transfusion from another person
3) EPO injections
Erythrocytes- Anemia
Anemia defined as Insufficient RBCs or hemoglobin
• Hematocrit below 35%  insufficient hemoglobin
• Iron-deficiency anemia – insufficient iron
• Pernicious anemia – due to lack of intrinsic
factor needed for absorption of vitamin B12 in
stomach….B12 necessary for RBC production
• Hemorrhagic anemia – due to excessive bleeding
• Hemolytic anemia – due to lysis (rupture) of RBC
caused by parasites, toxins, antibodies, or hemoglobin defects
• Aplastic anemia – due to lack of red bone marrow
activity caused by radiation or chemotherapy, or toxins
• Sickle cell anemia
– genetic disorder- that modifies the structure of Hb (HbS)
• mutation of Hb gene forms defective Hb molecule
• The mutated form of Hb produces crystals inside RBC
• RBC become sickle shaped incapable of transporting O2
• Misshaped RBC clogs blood capillaries
• Agglutination causes intense pain in O2 starved tissues
• Multiple symptoms -kidney/heart failure, stroke, paralysis
 Circulate for about 120 days
 Worn out RBC are phagocytized
by macrophages in spleen, liver
and bone marrow
 cell membranes are recycled 
hemoglobin degenerates:
1. globin protein  broken down
into amino acids -RECYCLED
to form new proteins
2. Heme (iron) breakdown:
• Fe (iron) is transported by
transferrin to bone marrow
where it is stored, recycled to
form new Hemoglobin, or
excreted
• Pigment converted by liver
to form bilirubin and urobilin
 form bile- excreted into
feces and urine
 Jaundice = inability of liver
to breakdown bilirubin
RBC Breakdown/
Transport/Storage
/ urine
18-24
Jaundice
Older children and adult therapy
for jaundice would depend on
what the underlying cause is for
the condition. (ie: gallstones)
Babies with jaundice are sometimes
treated with fluorescent light called
phototherapy. Bilirubin deposits in
the fatty tissue under the skin causing
the skin and whites of the eyes to
appear yellow. The skin absorbs the
light converting the bilirubin into
products that can be eliminated in the
stool and urine. The treatment is
usually done in a hospital but can be
done at home with proper equipment.
Blood Antigens
Antigens – cell markers/receptor
 complex protein molecules ON SURFACE
OF CELL MEMBRANE that are unique to the
individual. Used to provoke an immune
response
 distinguishes self from foreign
 foreign antigens markers generate an immune
response
 RBC antigens (complex protein molecules on
surface of cell membrane) are called
agglutinogens –they are the basis for blood
typing
 Two types of agglutinogens - antigen A and B
 type A person has A antigens
 type B person has B antigens
 type AB has both A and B antigens
 rarest - type AB
 type O person has neither antigen
 most common - type O
18-26
http://legacy.owensboro.kctcs.edu/gcaplan/anat2/histology/Image326.gif
18-27
http://smithlhhsb122.wikispaces.com/file/view/11-8_bloodtypes.png/473780846/404x304/11-8_bloodtypes.png
18-28
Blood Antibodies
Antibodies (agglutinins - produce agglutination); Anti-A; Anti-B
– appear 2-8 mos. after birth; reach maximum concentration at age 10
– antibody-A and/or antibody-B (both or none) PRESENT IN THE
BLOOD PLASMA NOT ON THE CELLS
– do not form antibodies against your own antigens
– Made of proteins (gamma globulins) secreted by plasma cells
– participates in immune response to foreign matter
– bind to antigens and mark them for destruction
– forms antigen-antibody complexes
• Specific interactions between antigens and antibodies are the
result of BLOOD TYPES. The ABO blood types are determined by
presence or absence of antigens (agglutinogens) on RBCs.
• Antibodies recognize and bind to specific antigens  cause
clumping of cells  AGGLUTINATION
• Blood transfusion require compatibility between PLASMA antibody
proteins and RBC- erythrocytes. Currently thirty-three (33) human
blood group systems define distinctive antigens/markers on blood
cells. We will discuss 2 of those systems; ABO and Rh.
• Cross-matching: mix donor and recipient blood for compatibility
using commercially available specific agglutinins or antibodies
18-29
“Antigen”
•
•
•
•
Blood type A has antibody B (anti-B) in its plasma
Blood type B has antibody A (anti-A) in its plasma
Blood type AB has NO antibodies in its plasma
Blood type O has both antibody A (anti-A) and antibody B (anti-B)
in its plasma
18-30
ABO Blood Typing
ANTIBODIES
Anti A
Antibodies attack and
agglutinate foreign antigens
Anti B
• Antibodies called agglutinins found
IN PLASMA are anti-A and anti-B
Type A
• What blood type is anti-A going to
agglutinate?(A) What blood type is
anti-B going to agglutinate? (B)
Type AB
• AB blood type has neither A or B
antibodies or it would continually clot
itself. If you add antibodies to AB
blood it will clot.
Type O
• O Blood type has both antibodies
and can only receive O type blood.
Type B
18-32
https://www.softchalk.com/lessonchallenge09/lesson/ImmuneSystems/Blood_009006.jpg
Agglutination of Erythrocytes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
“Foreign”
RBC cell with
antigen marker
(agglutinogens)
Antibodies
(agglutinins)
that recognize
foreign cells
and clump them
together
18-33
Agglutination
1. antibody molecule binding to
foreign antigens
2. causes clumping of red blood
cells
3. each antibody can attach to
SEVERAL foreign antigens
on several different RBCs at
the same time
4. responsible for mismatched
transfusion reaction
5. agglutinated RBCs block small
blood vessels, hemolyze, and
release their hemoglobin over
the next few hours or days
 Hb blocks kidney tubules
and causes acute renal
failure
Blood from
type A donor
Type B
(anti-A)
recipient
Donor RBCs
agglutinated by
recipient plasma
Agglutinated RBCs
block small vessels
18-34
Rh (Rhesus) Blood Group System
• Two types: Rh+ and Rh• Rh antigen (ANTIGEN D) “present” on RBC of Rh+
blood type
 (+) sign is an indication that antigen marker is
“PRESENT” on RBC
• Rh antigen is “ABSENT” on Rh- blood type
 (-) is indication that antigen marker is NOT present
on RBC
• Anti-D antibody will be produced if a person with Rhblood is given a transfusion of Rh+ blood
– RESULT: the person starts making Rh antibody (anti-D).
– Anti-D is ONLY present in Rh negative blood
Blood Groups
Rh Factor
• First pregnancy Rh- mother
is carrying Rh+ fetus  if
mixing of blood occurs at
birth, mother's body starts
making Rh antibodies
• During 2nd pregnancy if the fetus is Rh+ mother’s Rh antibodies cross
placenta  agglutinate fetal RBC  hemolysis (Rhesus Disease Rh)  fetal death
• RhoGAM, RHO (D) Immune Globulin (antibody) shot is given to the
mother to prevent miscarriage or harm to the fetus  antibody binds to
FETAL RBC that may have entered the mother  removes it from body
before mother makes Rh antibody. Tricks the mother’s body
– The mother’s body detects the RHO D antibodies, and reacts as though
her own immune system had already taken action against the “foreign”
Rh-positive RBCs cells.With the widespread use of the injection Rh
disease of the fetus and newborn have almost disappeared.
– RhoGAM is usually not administered until the 28th week of
pregnancy, and then again within 72 hours after delivery.
Universal Donors and Recipients
• universal donor
– Type O negative (–) most common blood type
– lacks Red Blood Cell antigens so recipient’s
antibodies will not agglutinate
– donor’s plasma (anti-A and anti-B) antibodies are in
low enough volume that they do not usually cause
not a problem
• may give packed cells (minimal plasma)
• universal recipient
– Type AB – rarest blood type
– lacks plasma antibodies; no anti- A or B; can
receive A, B, AB, O
18-37
Leukocytes- White Blood Cells
1. Migrate in and out of the
blood
2. Mostly found in connective
tissues and lymphoid
organs
• Less than 1% of the
formed elements
• 5,000 – 10,000 WBC / cu
mm of blood
• Conspicuous nucleus
• DO NOT HAVE
HEMOGLOBIN
• Plasma membrane has
histocompatibility antigens
– used to match cells,
tissues and organs
during donation
procedures
• Protect the body from
infections
• A Differential Blood
Count determines the % of
the 5 times of WBC types
Types of Leukocytes
• Granulocytes- Specific granules that contain enzymes or
chemicals for DEFENSE against pathogens and stain
conspicuously distinguishing each cell from others
– neutrophils (60-70%)
• barely-visible granules in cytoplasm; 3 to 5 lobed nucleus
– eosinophils (2- 4%)
• large rosy-orange granules; bilobed nucleus
– basophils (<1%)
• large, abundant, violet granules (obscure a large S-shaped
nucleus)
• Agranulocytes - Non-specific granules (lysosomes containing
enzymes in the cytoplasm) are inconspicuous to the light
microscope and have relatively clear looking cytoplasm.
– lymphocytes (25-33%) [B and T]
• variable amounts of bluish cytoplasm (scanty to abundant);
ovoid/round, uniform dark violet nucleus
– monocytes (3-8%)
• largest WBC; ovoid, kidney or horseshoe shaped nucleus
Formed Elements of Blood
18-40
Granulocyte Functions
• neutrophils - increased numbers in BACTERIAL INFECTIONS
– Active phagocytosis of bacteria
– release antimicrobial chemicals
• eosinophils - increased numbers in PARASITIC INFECTIONS,
collagen diseases, ALLERGIES, diseases of spleen and CNS
– phagocytosis of antigen-antibody complexes, allergens, and
inflammatory chemicals
– release enzymes to destroy large parasites = tapeworms, round
worms
– Not abundant in blood; found in mucus membranes of the
respiratory, digestive, and urinary tracts
• basophils - stimulate ALLERGIC REACTIONS; increased numbers in
chicken pox, sinusitis, diabetes
– secrete histamine (vasodilator) – widens blood vessels and
speeds flow of blood to an injured area
– secrete heparin (anticoagulant –blood thinner) – promotes the
mobility of other WBCs in the area by preventing blood clotting
– Stimulates the release of neutrophils and eosinophils to sites of
infection
– Become modified Mast Cells present in connective tissue
Agranulocyte Functions
• lymphocytes - increased numbers in diverse infections and
immune responses
– Two types “T” and “B”(antibodies)
– destroy cells (cancer, foreign, and virally infected cells)
– “present” antigens of pathogens to activate other immune cells
– coordinate actions of other immune cells
– secrete antibodies and provide immune memory
• monocytes - increased numbers in viral infections and
inflammation [no antibody for viral infection]
– leave bloodstream and transform into macrophages inside
tissues
• phagocytize pathogens and debris
• “present” antigens to activate other immune cells - antigen
presenting cells (APCs) “= chops” up pathogen and
displays it on the surface to alert the presence of foreign
substances
Leukocyte Life Cycle
• Leukopoiesis – production of white blood cells in red bone marrow and
lymphoid tissue (spleen, thymus, lymph nodes)
• Hemopoietic pluripotent stem cells in red bone marrow divide to form
– Myeloid stem cells (4 of the 5 WBC and the platelets)
• myeloblasts – form neutrophils, eosinophils, basophils
• monoblasts - form monocytes
• megakaryoblast -Platelets
– Lymphoid stem cells (1 type of WBC)
• lymphoblasts give rise to all forms of lymphocytes- T and B cells
– T lymphocytes complete development in thymus
• Red bone marrow stores and releases neutrophils, eosinophils, basophils
and monocytes; lymphocytes begin development in red bone marrow;
some mature there others migrate to thymus for maturation
• WBCs blood activity
– granulocytes (N-E-B) leave in 8 hours and live 5 days longer
– monocytes leave in 20 hours, transform into macrophages and live for
several years
– lymphocytes provide long-term immunity (decades) being continuously
recycled from blood to tissue fluid to lymph and back to the blood
18-43
Disorders
Leukocytosis (“cyto”=cell “sis”= process): when leukocyte number
increases ABOVE 10,000/cu mm of blood
– causes: infection, allergy and disease
Leukopenia (“penia”=deficiency): when leukocyte number decreases
BELOW 5,000/cu mm of blood
– Caused by: radiation, poisons, infectious disease (flu, measles, mumps)
– Primary effect of leukopenia is elevated risk of infection
Leukemia (“emia”= blood condition): CANCER OF LEUKOCYTES
– accumulation of immature (acute) or mature leukocytes (chronic)large amounts spill into blood replacing RBC, platelets, granulocytes.
Reduces competency of immune system to infection
– myeloid leukemia – uncontrolled granulocyte (N,E,B) monocyte,
production
– lymphoid leukemia - uncontrolled lymphocytes, crowd normal cells
• acute leukemia – appears suddenly, progresses rapidly, death
within months unless treated. Early detection can prolong life,
better prognosis due to increase in more effective therapy
• chronic leukemia –undetected for months, slow progression,
survival time three years
• Opportunistic infections – pathogenic organisms develop that would not
usually mount an infection in a healthy immunocompetent individual
– Decrease RBC = anemia; Decrease platelets= hemorrhage
Normal and Leukemic Blood
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Platelets
Monocyte
Neutrophils
Lymphocyte
Erythrocytes
(a)
(b)
75 µm
© Ed Reschke
18-46
Platelets
 Thrombocytes- platelets - small cytoplasmic fragments of
megakaryocytes
 normal platelet count - 250,000 – 400,000 platelets/L
1. secrete vasoconstrictors that help reduce blood loss
2. stick together to form platelet plugs to seal small breaks
3. secrete clotting factors
4. attract neutrophils and monocytes to sites of inflammation
5. phagocytize and destroy bacteria
6. Secrete growth factors to stimulate
fibroblasts to maintain and repair blood
vessels
 Circulate for 5-9 days in the blood stream
Thrombocytosis: when # of platelets goes UP  excessive clots
formation
Thrombocytopenia: when # of platelets goes DOWN  excessive
internal bleeding
18-47
Platelet
Formation:
Thrombopoiesis
 pluripotent cells divide to form proerythroblast, myeloblast,
monoblast, lymphoblast and megakaryoblast
 megakaryoblast duplicates its DNA repeatedly without dividing
forming a megakaryocyte
 megakaryocyte sprouts long tendrils called proplatelets that
protrude into the endothelium of blood capillaries
 the moving flow of blood breaks off the proplatelets which break
into platelets that travel through the blood
18-48
Hemostasis: Cessation of bleeding
• Prevents hemorrhage (loss of a large amount of blood)
• Steps involved
1. vascular spasm
2. platelet plug formation
3. coagulation = blood clotting
• Requires Calcium and Vitamin K (necessary for
synthesis of 4 clotting factors).
(a) Vascular spasm
(b) Platelet plug formation
(c)
Coagulation
Hemostasis - Vascular spasm
 Immediate protection for blood loss.
 Lasts approx. 30 minutes following injury
• Contraction of smooth muscle in the wall
of the blood vessels REDUCES
DIAMETER OF THE VESSEL at the site
of the injury and decreases blood flow
– Endothelial cells lining blood vessel
RELEASE chemical factors, ADP, local
hormones, and endothelins that
stimulate smooth muscle
contraction.
• Chemicals also facilitate formation
of platelet plug
– Endothelial plasma membranes
become “sticky”; attach to one another
across the breach sealing off blood
flow; also helps to provides attachment
site for platelets.
• Allows time for other two clotting pathways
to initiate
Hemostasis –Platelet Plug
Platelets detect damaged or punctured cells within a blood vessel.
1. Blood in motion does not clot due to the presence of
“PROSTACYCLIN” (platelet repellent). If it were not present and
the blood flow stopped, clotting would begin immediately.
2. The damage to the vessel wall disrupts the prostacyclin and
allows nearby platelets to adhere to any open surface. Once
attached to the wall, A) the platelets grow tendrils
(pseudopods) which B) bind to one another and CONTRACTdrawing the walls of the vessel together (platelet adhesion).
3. As the PLATELETS join, they RELEASE GRANULES
(degranulation) containing ADP, clotting and growth factors,
to increase blood synthesis and to seal the damaged area.
 The granules also release chemicals to attract other platelets. This
helps to make the platelet clot more effective; ADP plays a role in
drawing nearby platelets to those adhering to the vessel wall
4. The endothelial cells have become sticky. This “stickiness”
enables the platelets to fully seal any damage in the blood
vessel, and the plug is complete (platelet aggregation).
ADP attracts
free platelets to
those fixed to
vessel wall
Platelets grow
pseudopods;
adhere to one
another, draw
broken vessel
walls together
18-52
http://dc120.4shared.com/doc/CugMQMrP/preview_html_m758138cd.jpg
Platelet Plug
Formation
18-53
Hemostasis – Coagulation –Most Effective
Goal of clotting is to convert plasma protein fibrinogen into fibrinsticky protein that adheres to the vessel wall. Involves over 30
chemical reactions. Occurs within 30 seconds after injury
a
CLOT: a soft mass of protein fibers and blood cells
Substances needed for clot formation:
Ca2+, enzymes from liver, chemicals released by
platelets, chemicals released by damaged cells
Vitamin K: made by intestinal bacteria
Initially two pathways:
> Intrinsic pathway (contact activation pathway)
> Extrinsic pathway (tissue factor pathway)
– Primary pathway for the initiation of coagulation
Common pathway
Both form a common pathway
1. Prothrombinase and Ca2+ convert prothrombin  thrombin
2. Thrombin and Ca2+ convert soluble fibrinogen  insoluble fibrin fibers
3. Fibrin fibers trap blood cells  a soft mass –clot is formed
18-55
Hemostasis – EXTRINSIC pathway
Triggered by tissue damage OUTSIDE OF THE BLOOD VESSEL. Acts to
clot blood that has escaped from the vessel into the tissues; clotting factors
(proteins produced by the liver) come from damaged vessel and tissue
It was previously thought that the coagulation cascade consisted of two
pathways of EQUAL importance joined to a common pathway. It is now
known that the PRIMARY pathway for the initiation of blood coagulation is
the tissue factor or EXTRINSIC PATHWAY
• The pathways are a series of reactions, where a zymogen (inactive enzyme
precursor) are activated to catalyze the next reaction in the cascade,
ultimately resulting in cross-linked fibrin.
• Rapid process….takes place within seconds. Once one factor is activated it
will stimulate the activation of the next
• Initiated by releases of tissue factor thromboplastin (factor III) from
damaged tissue combines with factor VII and Ca2+ to activate factor X
factor X  prothrombinase is formed
COMMON PATH: Prothrombinase and Ca2+convert prothrombin  thrombin
> Thrombin and Ca2+ convert soluble fibrinogen  insoluble fibrin fibers.
> Fibrin fibers trap blood cells  a soft mass – clot formed
Good Animation:
http://www.youtube.com/watch
?v=036GFPRH5-w
18-57
Hemostasis – INTRINSIC pathway
Triggered by elements that lie
within the BLOOD ITSELF. More
complex slower process….takes place
within minutes
Damaged endothelial lining of blood
vessels  platelets come in contact with
collagen fibers in the basement
membrane  platelets are damaged and
release  factors –XII, X, phospholipids
and Ca2+  activated X, factor V and Ca2+
combine  prothrombinase is formed
COMMON PATH: Then prothrombinase
and Ca2+ convert prothrombin  thrombin.
Thrombin and Ca2+ convert soluble
fibrinogen  insoluble fibrin fibers.
Fibrin fibers trap blood cells  a soft
mass –clot is formed
Clot retraction, repair of the blood vessel and fibrinolysis
Clot temporarily seals the blood vessel platelets pull on the fibrin fibers
causing the clot to retract and pull the edges closer; endothelial cells and
fibroblasts divide to heal the blood vessel.
• An outside clot  dries  forms a scab; as tissue heals, scab fall off
Fibrinolysis
• Thrombus (clot) inside blood vessel slowly dissolves through
fibrinolysis- fibrin degeneration.
– inactive liver plasma enzyme –plasminogen converted to the active
enzyme = PLASMIN (fibrin dissolving enzyme) that dissolves the clot
– Fibrinolytic agents such as Streptokinase increases plasmin formation
• Thrombolytic agents: chemicals that dissolve entire thrombus unlike
fibrinolytic agents such as plasmin which focus on dissolving fibrin.
• Anticoagulants: chemicals that PREVENT clot formation by reducing
the “stickiness” of the blood.
• Heparin (interferes with prothrombin activation) released by
white blood cells - basophils
• Warfarin (medication known as Coumadin) inhibits processing
of vitamin K
• Vitamin C-prevents platelet aggregation; lowers plasma
fibrinogen levels –alternative to aspirin
http://www.thrombosisadviser.com/html/images/library/haemostasis/fibrinolysis-clot-formation-PU.jpg
Fibrinolysis
http://img.tfd.com/mk/F/X2604-F-10.png
Hemostasis – Blood clotting Issues
Thrombosis: Abnormal clotting of blood inside an unbroken
blood vessel
Thrombus: (clot) can grow large enough to obstruct vessel –most
often occurs in veins where blood flow is slower and thrombin less
diluted; common in legs of inactive persons
Stasis: slower blood flow --- can cause thrombosis
Embolus: a traveling clot
A clot can detach  travel to other body parts  cause ischemia
(insufficient blood flow) and necrosis  leading to multisystem organ
failure
 Pulmonary embolism: an embolus lodged in lungs
: blockage of blood circulation in lungs
: detected by breathing difficulties
Infarction (tissue death) may occur if clot blocks blood supply to
an organ (MI or stroke)
Stroke: cause by embolus in blood vessel going to the brain
Hemophilia: genetic disorder of clotting deficiency- sex-linked (X
chromosome)
: due to absence of clotting factors (generally factors VIII and IX)
: treated with infusion of factors