1

CVS : Blood

The CVS : Blood

2

Fluids of the Body

• Cells of the body are serviced by 2 fluids

• blood

• composed of plasma and a variety of cells

• transports nutrients and wastes

• interstitial fluid

• bathes the cells of the body

• Nutrients and oxygen diffuse from the blood into the interstitial fluid & then into the cells

• Wastes move in the reverse direction

3

Functions of Blood

• Transportation

• O2, CO2, metabolic wastes, nutrients, heat & hormones

• Regulation

• helps regulate pH through buffers

• helps regulate body temperature

• coolant properties of water

• vasodilatation of surface vessels dump heat

• helps regulate water content of cells by interactions with dissolved ions and proteins

• Protection from disease & loss of blood 4

Physical Characteristics of

Blood

• Thicker (more viscous) than water and flows more slowly than

water

• Temperature of 100.4 degrees F (38 degrees C)

• pH 7.4 (7.35-7.45)

• 8 % of total body weight

• Blood volume

• 5 to 6 liters in average male

• 4 to 5 liters in average female

• hormonal negative feedback systems maintain constant blood volume and osmotic pressure

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COMPONENTS OF BLOOD

• Blood consists of 55% plasma and 45% formed elements

• Blood plasma consists of 91.5% water and 8.5% solutes.

• Principal solutes include proteins (albumins, globulins,

fibrinogen), nutrients, enzymes, hormones, respiratory

gases, electrolytes, and waste products.

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Components of Blood

• Hematocrit ▫ 55% plasma

▫ 45% cells

99% RBCs

< 1% WBCs and platelets

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Blood Plasma • 0ver 90% water

• 7% plasma proteins

• created in liver

• confined to bloodstream

• albumin

• maintain blood osmotic pressure

• globulins (immunoglobulins)

• antibodies bind to foreign substances called antigens

• form antigen-antibody complexes

• fibrinogen

• for clotting

• 2% other substances

• electrolytes, nutrients, hormones, gases, waste products

8

Formed Elements of Blood • Red blood cells ( erythrocytes )

• White blood cells ( leukocytes )

• granular leukocytes

• neutrophils, eosinophils, basophils

• agranular leukocytes

• lymphocytes = T cells, B cells, and natural killer cells

• monocytes

• Platelets (special cell fragments)

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FORMATION OF BLOOD

CELLS

• Blood cells are formed from pluripotent hematopoietic

stem cells

• Bone marrow may be obtained through aspiration or

biopsy. The sample is then sent to pathology for

examination.

• Originating from the pluripotent stem cells are the

myeloid stem cells and lymphoid stem cells.

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Hematocrit • Percentage of blood occupied by cells

• female normal range

• 38 - 46% (average of 42%)

• male normal range

• 40 - 54% (average of 46%)

• testosterone

• Anemia

• not enough RBCs or not enough hemoglobin

• Polycythemia

• too many RBCs (over 65%)

• dehydration, tissue hypoxia, blood doping in athletes

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Formation of Blood Cells

• Most blood cells types need to be continually replaced

• die within hours, days or weeks

• process of blood cells formation is hematopoiesis or

hemopoiesis

• In the embryo

• occurs in yolk sac, liver, spleen, thymus, lymph nodes &

red bone marrow

• In adult

• occurs only in red marrow of flat bones like sternum,

ribs, skull & pelvis and ends of long bones 12

Hematopoiesis

13

Blood Cells • Myeloid stem cells give rise to RBCs, platelets, and all WBCs

except for lymphocytes.

• Lymphoid stem cells give rise to lymphocytes.

• Myeloid stem cells differentiate into progenitor cells or

precursor cells (blast cells) which will develop into the actual

formed elements of blood.

• Lymphoid stem cells differentiate into pre-B and

prothymocytes which develop into B-lymphocytes and T-

lymphocytes, respectively.

• This process of hemopoiesis (or hematopoiesis) is stimulated

by several hematopoietic growth factors. These hematopoietic

growth factors stimulate differentiation and proliferation of the

various blood cells. 14

Stages of Blood Cell Formation • Pluripotent stem cells

• 0.1% of red marrow cells

• replenish themselves as they differentiate into either myeloid or lymphoid stem cells

• Myeloid stem cell line of development continues:

• progenitor cells(colony-forming units) no longer can divide and are specialized to form specific cell types

• example: CFU-E develops eventually into only red blood cells

• next generation is blast cells

• have recognizable histological characteristics

• develop within several divisions into mature cell types

• Lymphoid stem cell line of development

• pre-B cells & prothymocytes finish their development into B & T lymphocytes in the lymphatic tissue after leaving the red marrow

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Hemopoietic Growth Factors

• Regulate differentiation & proliferation

• Erythropoietin (EPO)

• produced by the kidneys increase RBC precursors

• Thrombopoietin (TPO)

• hormone from liver stimulates platelet formation

• Cytokines are local hormones of bone marrow

• produced by some marrow cells to stimulate proliferation in other marrow cells

• colony-stimulating factor (CSF) & interleukin stimulate WBC production

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Hormones

• Erythropoietin increases the number of RBC precursors.

• Thrombopoietin increases the number of platelet

precursors.

• Cytokins (colony-stimulating factors and interleukins)

increase the number of WBC precursors.

• Growth factors, available through recombinant DNA

technology, hold great potential for use in patients who

cannot normally form the blood cells.

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Red Blood Cells or Erythrocytes • Contain oxygen-carrying protein hemoglobin that gives blood its red

color

• 1/3 of cell’s weight is hemoglobin

• Biconcave disk 8 microns in diameter

• increased surface area/volume ratio

• flexible shape for narrow passages

• no nucleus or other organelles

• no cell division or mitochondrial ATP formation

• Normal RBC count

• male 5.4 million/drop ---- female 4.8 million/drop

• new RBCs enter circulation at 2 million/second 18

Hemoglobin

• Globin protein consisting of 4 polypeptide chains

• One heme pigment attached to each polypeptide chain

• each heme contains an iron ion (Fe+2) that can combine

reversibly with one oxygen molecule

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Transport of O2, CO2 and Nitric Oxide

• Each hemoglobin molecule can carry 4 oxygen molecules from

lungs to tissue cells

• Hemoglobin transports 23% of total CO2 waste from tissue cells

to lungs for release

• combines with amino acids in globin portion of Hb

• Hemoglobin transports nitric oxide & super nitric oxide helping to

regulate BP

• Fe ions pick up nitric oxide (NO) & super nitric oxide (SNO) &

transport it to & from the lungs

• NO causing vasoconstriction is released in the lungs

• SNO causing vasodilation is picked up in the lungs 20

RBC Life Cycle

• RBCs live only 120 days

• wear out from bending to fit through capillaries

• no repair possible due to lack of organelles

• Worn out cells removed by fixed macrophages in spleen &

liver

• Breakdown products are recycled

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Recycling of Hemoglobin Components

• In macrophages of liver or spleen

• globin portion broken down into amino acids & recycled

• heme portion split into iron (Fe+3) and biliverdin (green pigment) 22

Fate of Components of Heme • Iron(Fe+3)

• transported in blood attached to transferrin protein

• stored in liver, muscle or spleen

• attached to ferritin or hemosiderin protein

• in bone marrow being used for hemoglobin synthesis

• Biliverdin (green) converted to bilirubin (yellow)

• bilirubin secreted by liver into bile

• converted to urobilinogen then stercobilin (brown pigment in feces) by bacteria of large intestine

• if reabsorbed from intestines into blood is converted to a yellow pigment, urobilin and excreted in urine

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Erythropoiesis: Production of RBCs

• Erythrocyte formation, called erythropoiesis, occurs in adult red

bone marrow of certain bones

• The main stimulus for erythropoiesis is hypoxia

• Proerythroblast starts to produce hemoglobin

• Many steps later, nucleus is ejected & a reticulocyte is formed

▫ orange in color with traces of visible rough ER

• Reticulocytes escape from bone marrow into the blood

• In 1-2 days, they eject the remaining organelles to become a

mature RBC 24

Feedback Control of RBC Production

• Tissue hypoxia (cells not getting enough O2)

▫ high altitude since air has less O2

▫ anemia

RBC production falls below RBC destruction

▫ circulatory problems

• Kidney response to hypoxia

▫ release erythropoietin

▫ speeds up development of proerythroblasts into reticulocytes

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Normal Reticulocyte Count

• Should be .5 to 1.5% of the circulating RBC’s

• Low count in an anemic person might indicate bone marrow

problem

• leukemia, nutritional deficiency or failure of red bone marrow

to respond to erythropoietin stimulation

• High count might indicate recent blood loss or successful iron

therapy

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WHITE BLOOD CELLS

• Leukocytes (white blood cells or WBCs) are nucleated cells and do not contain hemoglobin. Two principal types are granular (neutrophils, eosinophils, basophils) and agranular (lymphocytes and monocytes) ▫ Granular leukocytes include eosinophils, basophils, and

neutrophils based on the straining of the granules.

▫ Agranular leukocytes do not have cytoplasmic granules and include the lymphocytes and monocytes, which differentiate into macrophages (fixed and wandering).

• Leukocytes have surface proteins, as do erythrocytes. They are called major histocompatibility antigens (MHC), are unique for each person (except for identical siblings), and can be used to identify a tissue.

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WBC Physiology • Less numerous than RBCs

• 5000 to 10,000 cells per drop of blood

• 1 WBC for every 700 RBC

• Leukocytosis is a high white blood cell count

• microbes, strenuous exercise, anesthesia or surgery

• Leukopenia is low white blood cell count

• radiation, shock or chemotherapy

• Only 2% of total WBC population is in circulating blood at any

given time

• rest is in lymphatic fluid, skin, lungs, lymph nodes & spleen

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Function of WBCs • Different WBCs combat inflammation and infection in different

ways.

▫ Neutrophils and wandering or fixed macrophages (which

develop from monocytes) do so through phagocytosis.

▫ Eosinophils combat the effects of histamine in allergic

reactions, phagocytize antigen-antibody complexes, and combat

parasitic worms.

▫ Basophils develop into mast cells that liberate heparin,

histamine, and serotonin in allergic reactions that intensify the

inflammatory response.

▫ B lymphocytes, in response to the presence of foreign

substances called antigens, differentiate into tissue plasma cells

that produce antibodies.

▫ T lymphocytes destroy foreign invaders directly.

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Function of WBCs

• WBCs leave the blood stream by emigration

• Some WBCs, particularly neutrophils and macrophages,

are active in phagocytosis.

• The chemical attraction of WBCs to a disease or injury

site is termed chemotaxis.

Principles of Human Anatomy and Physiology, 11e

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WBC examination

• A differential white blood cell count is a diagnostic test in

which specific white blood cells are enumerated. Because

each type of WBC plays a different role, determining the

percentage of each type in the blood assists in diagnosing

the condition.

• Bone marrow transplants may be used to treat several

types of anemia, leukemia, and numerous other blood

disorders.

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Neutrophils (Granulocyte)

• Polymorphonuclear Leukocytes or Polys

• Nuclei = 2 to 5 lobes connected by thin strands

• older cells have more lobes

• young cells called band cells because of horseshoe shaped

nucleus (band)

• Fine, pale lilac practically invisible granules

• Diameter is 10-12 microns

• 60 to 70% of circulating WBCs

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Eosinophils (Granulocyte)

• Nucleus with 2 or 3 lobes connected by a thin strand

• Large, uniform-sized granules stain orange-red with acidic

dyes

• do not obscure the nucleus

• Diameter is 10 to 12 microns

• 2 to 4% of circulating WBCs

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Basophils (Granulocyte)

• Large, dark purple, variable-sized granules stain with basic

dyes

• obscure the nucleus

• Irregular, s-shaped, bilobed nuclei

• Diameter is 8 to 10 microns

• Less than 1% of circulating WBCs

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Lymphocyte (Agranulocyte)

• Dark, oval to round nucleus

• Cytoplasm sky blue in color

• amount varies from rim of blue to normal amount

• Small cells 6 - 9 microns in diameter

• Large cells 10 - 14 microns in diameter

• increase in number during viral infections

• 20 to 25% of circulating WBCs

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Monocyte (Agranulocyte) • Nucleus is kidney or horse-shoe shaped

• Largest WBC in circulating blood

• does not remain in blood long before migrating to the tissues

• differentiate into macrophages

• fixed group found in specific tissues

• alveolar macrophages in lungs

• Kupffer cells in liver

• wandering group gathers at sites of infection

• Diameter is 12 - 20 microns

• Cytoplasm is a foamy blue-gray

• 3 to 8% o circulating WBCs

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Emigration & Phagocytosis in WBCs • WBCs roll along endothelium, stick to it

& squeeze between cells.

• adhesion molecules (selectins) help WBCs stick to endothelium

• displayed near site of injury

• molecules (integrins) found on neutrophils assist in movement through wall

• Neutrophils & macrophages phagocytize bacteria & debris

• chemotaxis of both

• kinins from injury site & toxins

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Neutrophil Function

• Fastest response of all WBC to bacteria

• Direct actions against bacteria

• release lysozymes which destroy/digest bacteria

• release defensin proteins that act like antibiotics & poke holes in

bacterial cell walls destroying them

• release strong oxidants (bleach-like, strong chemicals ) that

destroy bacteria

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Monocyte Function

• Take longer to get to site of infection, but arrive

in larger numbers

• Become wandering macrophages, once they

leave the capillaries

• Destroy microbes and clean up dead tissue

following an infection

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Basophil Function

• Involved in inflammatory and allergy reactions

• Leave capillaries & enter connective tissue as

mast cells

• Release heparin, histamine & serotonin

• heighten the inflammatory response and

account for hypersensitivity (allergic) reaction

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Eosinophil Function

• Leave capillaries to enter tissue fluid

• Release histaminase

• slows down inflammation caused by basophils

• Attack parasitic worms

• Phagocytize antibody-antigen complexes

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Lymphocyte Functions

• B cells

• destroy bacteria and their toxins

• turn into plasma cells that produces antibodies

• T cells

• attack viruses, fungi, transplanted organs, cancer cells & some

bacteria

• Natural killer cells

• attack many different microbes & some tumor cells

• destroy foreign invaders by direct attack

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Complete Blood Count

• Screens for anemia and infection

• Total RBC, WBC & platelet counts; differential WBC;

hematocrit and hemoglobin measurements

• Normal hemoglobin range

• infants have 14 to 20 g/100mL of blood

• adult females have 12 to 16 g/100mL of blood

• adult males have 13.5 to 18g/100mL of blood

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Differential WBC Count

• Detection of changes in numbers of circulating WBCs (percentages

of each type)

• indicates infection, poisoning, leukemia, chemotherapy, parasites

or allergy reaction

• Normal WBC counts

• neutrophils 60-70% (up if bacterial infection)

• lymphocyte 20-25% (up if viral infection)

• monocytes 3 -- 8 % (up if fungal/viral infection)

• eosinophil 2 -- 4 % (up if parasite or allergy reaction)

• basophil <1% (up if allergy reaction or hypothyroid) 44

PLATELETS

• Thrombopoietin stimulates myeloid stem cells to produce platelets.

• Myeloid stem cells develop into megakaryocyte-colony-forming cells

that develop into megakaryoblasts (Figure 19.2).

• Megakaryoblasts transform into megakaryocytes which fragment.

• Each fragment, enclosed by a piece of cell membrane, is a platelet

(thrombocyte).

• Normal blood contains 250,000 to 400,000 platelets/mm3. Platelets

have a life span of only 5 to 9 days; aged and dead platelets are

removed by fixed macrophages in the spleen and liver.

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PLATELETS

• Platelets help stop blood loss from damaged vessels by

forming a platelet plug. Their granules also contain

chemicals that promote blood clotting.

• A complete blood count (CBC) is a test that screens for

anemia and various infections. It usually includes counts

of RBCs, WBCs, and platelets per μL of whole blood;

hematocrit and differential white blood cell count. The

amount of hemoglobin in grams per ml is also

determined.

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Platelet

(Thrombocyte)

Anatomy

• Disc-shaped, 2 - 4 micron cell fragment with no

nucleus

• Normal platelet count is 150,000-400,000/drop of

blood

• Other blood cell counts

• 5 million red & 5-10,000 white blood cells

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Platelets--Life History • Platelets form in bone marrow by following steps:

• myeloid stem cells to megakaryocyte-colony forming

cells to megakaryoblast to megakaryocytes whose cell

fragments form platelets

• Short life span (5 to 9 days in bloodstream)

• formed in bone marrow

• few days in circulating blood

• aged ones removed by fixed macrophages in liver and

spleen

48

HEMOSTASIS • A clot is a gel consisting of a network of insoluble protein

fibers (fibrin) in which formed elements of blood are trapped

• The chemicals involved in clotting are known as coagulation

(clotting) factors; most are in blood plasma, some are released

by platelets, and one is released from damaged tissue cells

• Blood clotting involves a cascade of reactions that may be

divided into three stages: formation of prothrombinase

(prothrombin activator), conversion of prothrombin into

thrombin, and conversion of soluble fibrinogen into insoluble

fibrin 49

HEMOSTASIS

• The clotting cascade can be initiated by either the extrinsic

pathway or the intrinsic pathway.

• Normal coagulation requires vitamin K and also involves clot

retraction (tightening of the clot) and fibrinolysis (dissolution

of the clot).

• The fibrinolytic system dissolves small, inappropriate clots

and clots at a site of damage once the damage is repaired.

• Plasmin (fibrinolysin) can dissolve a clot by digesting fibrin

threads and inactivating substances such as fibrinogen,

prothrombin, and factors V, VIII, and XII.

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Hemostasis

• Stoppage of bleeding in a quick & localized fashion when blood

vessels are damaged

• Prevents hemorrhage (loss of a large amount of blood)

• Methods utilized

• vascular spasm

• platelet plug formation

• blood clotting (coagulation = formation of fibrin threads)

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Vascular Spasm

• Damage to blood vessel produces stimulates pain

receptors

• Reflex contraction of smooth muscle of small blood

vessels

• Can reduce blood loss for several hours until other

mechanisms can take over

• Only for small blood vessel or arteriole

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Platelet Plug Formation • Platelets store a lot of chemicals in granules needed for platelet

plug formation

• alpha granules

• clotting factors

• platelet-derived growth factor

• cause proliferation of vascular endothelial cells, smooth muscle & fibroblasts to repair damaged vessels

• dense granules

• ADP, ATP, Ca+2, serotonin, fibrin-stabilizing factor, & enzymes that produce thromboxane A2

• Steps in the process

• (1) platelet adhesion (2) platelet release reaction (3) platelet aggregation

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Platelet Adhesion

• Platelets stick to exposed collagen underlying

damaged endothelial cells in vessel wall

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Platelet Release Reaction

• Platelets activated by adhesion

• Extend projections to make contact with each other

• Release thromboxane A2 & ADP activating other

platelets

• Serotonin & thromboxane A2 are vasoconstrictors

decreasing blood flow through the injured vessel

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Platelet Aggregation

• Activated platelets stick together and activate new

platelets to form a mass called a platelet plug

• Plug reinforced by fibrin threads formed during

clotting process

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Blood Clotting • Blood drawn from the body thickens into a gel

• gel separates into liquid (serum) and a clot of insoluble fibers (fibrin) in which the cells are trapped

• If clotting occurs in an unbroken vessel is called a thrombosis

• Substances required for clotting are Ca+2, enzymes synthesized by liver cells and substances released by platelets or damaged tissues

• Clotting is a cascade of reactions in which each clotting factor activates the next in a fixed sequence resulting in the formation of fibrin threads

• prothrombinase & Ca+2 convert prothrombin into thrombin

• thrombin converts fibrinogen into fibrin threads

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Overview of the

Clotting Cascade

• Prothrombinase is formed by either

the intrinsic or extrinsic pathway

• Final common pathway produces

fibrin threads

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Extrinsic Pathway

• Damaged tissues leak tissue factor

(thromboplastin) into bloodstream

• Prothrombinase forms in seconds

• In the presence of Ca+2, clotting

factor X combines with V to form

prothrombinase

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Intrinsic Pathway

• Activation occurs

• endothelium is damaged & platelets

come in contact with collagen of

blood vessel wall

• platelets damaged & release

phospholipids

• Requires several minutes for

reaction to occur

• Substances involved: Ca+2 and

clotting factors XII, X and V 60

Final Common Pathway • Prothrombinase and Ca+2

• catalyze the conversion of prothrombin to thrombin

• Thrombin

• in the presence of Ca+2 converts soluble fibrinogen to insoluble fibrin threads

• activates fibrin stabilizing factor XIII

• positive feedback effects of thrombin

• accelerates formation of prothrombinase

• activates platelets to release phospholipids

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Clot Retraction & Blood Vessel

Repair

• Clot plugs ruptured area of blood

vessel

• Platelets pull on fibrin threads

causing clot retraction

• trapped platelets release factor XIII

stabilizing the fibrin threads

• Edges of damaged vessel are pulled

together

• Fibroblasts & endothelial cells repair

the blood vessel

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Role of Vitamin K in Clotting

• Normal clotting requires adequate vitamin K

• fat soluble vitamin absorbed if lipids are present

• absorption slowed if bile release is insufficient

• Required for synthesis of 4 clotting factors by hepatocytes

• factors II (prothrombin), VII, IX and X

• Produced by bacteria in large intestine

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Hemostatic Control Mechanisms • Fibrinolytic system dissolves small, inappropriate clots & clots at a

site of a completed repair

• fibrinolysis is dissolution of a clot

• Inactive plasminogen is incorporated into the clot

• activation occurs because of factor XII and thrombin

• plasminogen becomes plasmin (fibrinolysin) which digests fibrin threads

• Clot formation remains localized

• fibrin absorbs thrombin

• blood disperses clotting factors

• endothelial cells & WBC produce prostacyclin that opposes thromboxane A2 (platelet adhesion & release)

• Anticoagulants present in blood & produced by mast cells

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Intravascular Clotting • Thrombosis

• clot (thrombus) forming in an unbroken blood vessel

• forms on rough inner lining of BV

• if blood flows too slowly (stasis) allowing clotting factors to build up locally & cause coagulation

• may dissolve spontaneously or dislodge & travel

• Embolus

• clot, air bubble or fat from broken bone in the blood

• pulmonary embolus is found in lungs

• Low dose aspirin blocks synthesis of thromboxane A2 & reduces inappropriate clot formation

• strokes, TIAs and myocardial infarctions 65

Anticoagulants and Thrombolytic Agents

• Anticoagulants suppress or prevent blood clotting

▫ heparin

administered during hemodialysis and surgery

▫ warfarin (Coumadin)

antagonist to vitamin K so blocks synthesis of clotting factors

slower than heparin

▫ stored blood in blood banks treated with citrate phosphate dextrose (CPD) that removes Ca+2

• Thrombolytic agents are injected to dissolve clots

▫ directly or indirectly activate plasminogen

▫ streptokinase or tissue plasminogen activator (t-PA)

66

Hemostatic Control

Mechanisms

• Clots are generally localized due to fibrin absorbing thrombin into the clot, clotting factors diffusing through blood, and the production of prostacyclin, a powerful inhibitor of platelet adhesion and release.

• Substances that inhibit coagulation, called anticoagulants, are also present in blood. An example is heparin.

• Patients who are at increased risk of forming blood clots may receive an anticoagulant drug such as heparin or warfarin. To prevent clots in donated blood, a substance that removes Ca+2

such as EDTA or CPD may be added to the blood.

• Despite the anticoagulating and fibrinolytic mechanisms, blood clots sometimes form within the cardiovascular system.

67

HEMOSTASIS

• Clotting in an unbroken blood vessel is called thrombosis.

• A thrombus (clot), bubble of air, fat from broken bones, or piece of debris transported by the bloodstream that moves from its site of origin is called an embolus.

• At low doses aspirin inhibits vasoconstriction and platelet aggregation thereby reducing the chance of thrombus formation. Thrombolytic agents are injected into the body to dissolve clots that have already formed. Streptokinase or tissue plasminogen activator (TPS) are thrombolytic agents.

68

ABO Group

• In the ABO system, agglutinogens (antigens) A and B

determine blood types

• Plasma contains agglutinins (antibodies), designated as a

and b, that react with agglutinogens that are foreign to the

individual.

Principles of Human Anatomy and Physiology, 11e

69

Blood Groups and Blood Types

• RBC surfaces are marked by genetically determined glycoproteins & glycolipids

• agglutinogens or isoantigens

• distinguishes at least 24 different blood groups

• ABO, Rh, Lewis, Kell, Kidd and Duffy systems

70

ABO Blood Groups • Based on 2 glycolipid isoantigens called A and B found on the

surface of RBCs

▫ display only antigen A -- blood type A

▫ display only antigen B -- blood type B

▫ display both antigens A & B -- blood type AB

▫ display neither antigen -- blood type O

• Plasma contains isoantibodies or agglutinins to the A or B antigens

not found in your blood

▫ anti-A antibody reacts with antigen A

▫ anti-B antibody reacts with antigen B

71

RH blood groups

• Antigen was discovered in blood of Rhesus monkey

• People with Rh agglutinogens on RBC surface are Rh+. Normal

plasma contains no anti-Rh antibodies

• Antibodies develop only in Rh- blood type & only with exposure to

the antigen

• transfusion of positive blood

• during a pregnancy with a positive blood type fetus

• Transfusion reaction upon 2nd exposure to the antigen results in

hemolysis of the RBCs in the donated blood 72

Hemolytic Disease of Newborn

• Rh negative mom and Rh+ fetus will have mixing of blood at birth

• Mom's body creates Rh antibodies unless she receives a RhoGam shot soon after first delivery, miscarriage or abortion

• RhoGam binds to loose fetal blood and removes it from body before she reacts

• In 2nd child, hemolytic disease of the newborn may develop causing hemolysis of the fetal RBCs

73

Transfusion and Transfusion Reactions

• Transfer of whole blood, cells or plasma into the bloodstream of

recipient

• used to treat anemia or severe blood loss

• Incompatible blood transfusions

• antigen-antibody complexes form between plasma antibodies

& “foreign proteins” on donated RBC's (agglutination)

• donated RBCs become leaky (complement proteins) & burst

• loose hemoglobin causes kidney damage

• Problems caused by incompatibility between donor’s cells and

recipient’s plasma

• Donor plasma is too diluted to cause problems

74

Universal Donors and Recipients

• People with type AB blood called “universal

recipients” since have no antibodies in plasma

• only true if cross match the blood for other antigens

• People with type O blood cell called “universal

donors” since have no antigens on their cells

• theoretically can be given to anyone

75

Typing and Cross-Matching

Blood for Transfusion

• The Rh and ABO blood groups may be detected by a

simple medical test, blood typing, in which a sample of

blood is mixed with serum containing agglutinins to each

of the major agglutinogens (AB, B, and Rh)

• Typing is the determination of blood types, whereas

cross-matching is the mixing of donor and recipient blood

for compatibility.

76

DISORDERS: HOMEOSTATIC

IMBALANCES

• Anemia

• Sickle-cell

• Hemophilia

• Disseminated intravascular clotting

• Acute leukemia

• Chronic leukemia

77

Anemia = Not Enough RBCs • Symptoms

• oxygen-carrying capacity of blood is reduced

• fatigue, cold intolerance & paleness

• lack of O2 for ATP & heat production

• Types of anemia

• iron-deficiency =lack of absorption or loss of iron

• pernicious = lack of intrinsic factor for B12 absorption

• hemorrhagic = loss of RBCs due to bleeding (ulcer)

• hemolytic = defects in cell membranes cause rupture

• thalassemia = hereditary deficiency of hemoglobin

• aplastic = destruction of bone marrow (radiation/toxins) 78

Sickle-cell Anemia (SCA)

• Genetic defect in hemoglobin molecule (Hb-S) that changes 2 amino

acids

• at low O2 levels, RBC is deformed by changes in hemoglobin molecule within the RBC

• sickle-shaped cells rupture easily = causing anemia & clots

• Found among populations in malaria belt

• Mediterranean Europe, sub-Saharan Africa & Asia

• Person with only one sickle cell gene

• increased resistance to malaria because RBC membranes leak K+ & lowered levels of K+ kill the parasite infecting the red blood cells 79

Hemophilia • Inherited deficiency of clotting factors

• bleeding spontaneously or after minor trauma

• subcutaneous & intramuscular hemorrhaging

• nosebleeds, blood in urine, articular bleeding & pain

• Hemophilia A lacks factor VIII (males only)

• most common

• Hemophilia B lacks factor IX (males only)

• Hemophilia C (males & females)

• less severe because alternate clotting activator exists

• Treatment is transfusions of fresh plasma or concentrates of the missing clotting factor

80

Disseminated Intravascular

Clotting • Life threatening paradoxical presence of blood clotting and

bleeding at the same time throughout the whole body

• so many clotting factors are removed by widespread clotting

that too few remain to permit normal clotting

• Associated with infections, hypoxia, low blood flow rates,

trauma, hypotension & hemolysis

• Clots cause ischemia and necrosis leading to multisystem organ

failure

81

Leukemia

• Acute leukemia

• uncontrolled production of immature leukocytes

• crowding out of normal red bone marrow cells by production of

immature WBC

• prevents production of RBC & platelets

• Chronic leukemia

• accumulation of mature WBC in bloodstream because they do

not die

• classified by type of WBC that is predominant---monocytic,

lymphocytic. 82