Blood Composition Blood

Fluid connective tissue Plasma non-living fluid matrix Formed elements living blood "cells" suspended in plasma
Erythrocytes (red blood cells, or RBCs) Leukocytes (white blood cells, or WBCs) Platelets

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Blood Composition Spun tube of blood yields three layers

Plasma on top (~55%) Erythrocytes on bottom (~45%) WBCs and platelets in Buffy coat (< 1%)

Hematocrit
Percent of blood volume that is RBCs 47% 5% for males; 42% 5% for females

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Figure 17.1 The major components of whole blood.

Slide 1

Formed elements Plasma 55% of whole blood Least dense component Buffy coat Leukocytes and platelets <1% of whole blood Erythrocytes 45% of whole blood (hematocrit) Most dense component

1 Withdraw blood and place in tube.

2 Centrifuge the blood sample.

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Physical Characteristics and Volume Sticky, opaque fluid with metallic taste Color varies with O2 content
High O2 - scarlet; Low O2 - dark red

pH 7.357.45 ~8% of body weight Average volume

56 L for males; 45 L for females

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Functions of Blood Functions include

Distributing substances Regulating blood levels of substances Protection

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Distribution Functions Delivering O2 and nutrients to body cells Transporting metabolic wastes to lungs and kidneys for elimination Transporting hormones from endocrine organs to target organs

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Regulation Functions Maintaining body temperature by absorbing and distributing heat Maintaining normal pH using buffers; alkaline reserve of bicarbonate ions Maintaining adequate fluid volume in circulatory system

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Protection Functions Preventing blood loss

Plasma proteins and platelets initiate clot formation

Preventing infection
Antibodies Complement proteins WBCs

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Blood Plasma 90% water Over 100 dissolved solutes

Nutrients, gases, hormones, wastes, proteins, inorganic ions Plasma proteins most abundant solutes
Remain in blood; not taken up by cells Proteins produced mostly by liver 60% albumin; 36% globulins; 4% fibrinogen

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Table 17.1 Composition of Plasma (1 of 2)

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Table 17.1 Composition of Plasma (2 of 2)

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Albumin 60% of plasma protein Functions

Substance carrier Blood buffer Major contributor of plasma osmotic pressure

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Formed Elements Only WBCs are complete cells RBCs have no nuclei or other organelles Platelets are cell fragments Most formed elements survive in bloodstream only few days Most blood cells originate in bone marrow and do not divide

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Figure 17.2 Photomicrograph of a human blood smear stained with Wright's stain.

Platelets

Erythrocytes

Monocyte

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Neutrophils

Lymphocyte

Erythrocytes Biconcave discs, anucleate, essentially no organelles Diameters larger than some capillaries Filled with hemoglobin (Hb) for gas transport Contain plasma membrane protein spectrin and other proteins
Spectrin provides flexibility to change shape

Major factor contributing to blood viscosity

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Figure 17.3 Structure of erythrocytes (red blood cells).

2.5 m

Side view (cut)

7.5 m

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Top view

Erythrocytes Structural characteristics contribute to gas transport

Biconcave shapehuge surface area relative to volume >97% hemoglobin (not counting water) No mitochondria; ATP production anaerobic; do not consume O2 they transport

Superb example of complementarity of structure and function

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Erythrocyte Function RBCs dedicated to respiratory gas transport Hemoglobin binds reversibly with oxygen Normal values
Males - 1318g/100ml; Females - 1216 g/100ml

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Hemoglobin Structure Globin composed of 4 polypeptide chains

Two alpha and two beta chains

Heme pigment bonded to each globin chain

Gives blood red color

Heme's central iron atom binds one O2 Each Hb molecule can transport four O2 Each RBC contains 250 million Hb molecules
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Figure 17.4 Structure of hemoglobin.

Globin chains

Heme group

Globin chains Hemoglobin consists of globin (two alpha and two beta polypeptide chains) and four heme groups. Iron-containing heme pigment.

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Hemoglobin (Hb) O2 loading in lungs

Produces oxyhemoglobin (ruby red)

O2 unloading in tissues
Produces deoxyhemoglobin or reduced hemoglobin (dark red)

CO2 loading in tissues

20% of CO2 in blood binds to Hb carbaminohemoglobin

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Hematopoiesis Blood cell formation in red bone marrow

Composed of reticular connective tissue and blood sinusoids

In adult, found in axial skeleton, girdles, and proximal epiphyses of humerus and femur

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Hematopoiesis Hematopoietic stem cells (Hemocytoblasts)

Give rise to all formed elements Hormones and growth factors push cell toward specific pathway of blood cell development Committed cells cannot change

New blood cells enter blood sinusoids

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Erythropoiesis: Red Blood Cell Production Stages

Myeloid stem cell transformed into proerythroblast In 15 days proerythroblasts develop into basophilic, then polychromatic, then orthochromatic erythroblasts, and then into reticulocytes Reticulocytes enter bloodstream; in 2 days mature RBC

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Erythropoiesis As myeloid stem cell transforms

1. Ribosomes synthesized 2. Hemoglobin synthesized; iron accumulates 3. Ejection of nucleus; formation of reticulocyte (young RBC)

Reticulocyte ribosomes degraded; Then become mature erythrocytes Reticulocyte count indicates rate of RBC formation
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Figure 17.5 Erythropoiesis: formation of red blood cells.

Stem cell

Committed cell

Developmental pathway Phase 1 Ribosome synthesis Phase 2 Hemoglobin accumulation Phase 3 Ejection of nucleus

Hematopoietic stem cell (hemocytoblast)

Proerythroblast

Basophilic erythroblast

Polychromatic erythroblast

Orthochromatic erythroblast

Reticulocyte Erythrocyte

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Regulation of Erythropoiesis Too few RBCs leads to tissue hypoxia Too many RBCs increases blood viscosity > 2 million RBCs made per second Balance between RBC production and destruction depends on
Hormonal controls Adequate supplies of iron, amino acids, and B vitamins

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Hormonal Control of Erythropoiesis Hormone Erythropoietin (EPO)

Direct stimulus for erythropoiesis Always small amount in blood to maintain basal rate
High RBC or O2 levels depress production

Released by kidneys (some from liver) in response to hypoxia

Dialysis patients have low RBC counts

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Hormonal Control of Erythropoiesis Causes of hypoxia

Decreased RBC numbers due to hemorrhage or increased destruction Insufficient hemoglobin per RBC (e.g., iron deficiency) Reduced availability of O2 (e.g., high altitudes)

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Hormonal Control of Erythropoiesis Effects of EPO

Rapid maturation of committed marrow cells Increased circulating reticulocyte count in 1 2 days

Some athletes abuse artificial EPO

Dangerous consequences

Testosterone enhances EPO production, resulting in higher RBC counts in males

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Figure 17.6 Erythropoietin mechanism for regulating erythropoiesis.

Slide 1

Homeostasis: Normal blood oxygen levels 1 Stimulus: Hypoxia (inadequate O2 delivery) due to Decreased RBC count Decreased amount of hemoglobin Decreased availability of O2 2 Kidney (and liver to a smaller extent) releases erythropoietin.

5 O2-carrying ability of blood rises.

4 Enhanced erythropoiesis increases RBC count. 3 Erythropoietin stimulates red bone marrow.

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Dietary Requirements for Erythropoiesis

Nutrientsamino acids, lipids, and carbohydrates Iron
Available from diet 65% in Hb; rest in liver, spleen, and bone marrow Free iron ions toxic
Stored in cells as ferritin and hemosiderin Transported in blood bound to protein transferrin

Vitamin B12 and folic acid necessary for DNA synthesis for rapidly dividing cells (developing RBCs)
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Fate and Destruction of Erythrocytes Life span: 100120 days

No protein synthesis, growth, division

Old RBCs become fragile; Hb begins to degenerate Get trapped in smaller circulatory channels especially in spleen Macrophages engulf dying RBCs in spleen

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Fate and Destruction of Erythrocytes Heme and globin are separated

Iron salvaged for reuse Heme degraded to yellow pigment bilirubin Liver secretes bilirubin (in bile) into intestines
Degraded to pigment urobilinogen Pigment leaves body in feces as stercobilin

Globin metabolized into amino acids

Released into circulation

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Figure 17.7 Life cycle of red blood cells.

1 Low O2 levels in blood stimulate kidneys to produce erythropoietin. 2 Erythropoietin levels rise in blood. 3 Erythropoietin and necessary raw materials in blood promote erythropoiesis in red bone marrow.

Slide 1

4 New erythrocytes enter bloodstream; function about 120 days.

5 Aged and damaged red blood cells are engulfed by macrophages of spleen, liver, and bone marrow; the hemoglobin is broken down. Hemoglobin

Heme

Globin

Bilirubin is picked up by the liver.

Iron is stored as ferritin or hemosiderin.

Amino acids

Iron is bound to transferrin and released to blood from liver as needed for erythropoiesis.

Bilirubin is secreted into intestine in bile where it is metabolized to stercobilin by bacteria.

Circulation

6 Raw materials are made available in blood for erythrocyte synthesis.

Stercobilin is excreted in feces.

Food nutrients (amino acids, Fe, B12, and folic acid) are absorbed from intestine and enter blood.

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Erythrocyte Disorders Anemia

Blood has abnormally low O2-carrying capacity Sign rather than disease itself Blood O2 levels cannot support normal metabolism Accompanied by fatigue, pallor, shortness of breath, and chills

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Causes of Anemia Three groups

Blood loss Low RBC production High RBC destruction

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Causes of Anemia: Blood Loss Hemorrhagic anemia

Blood loss rapid (e.g., stab wound) Treated by blood replacement

Chronic hemorrhagic anemia

Slight but persistent blood loss
Hemorrhoids, bleeding ulcer

Primary problem treated

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Causes of Anemia: Low RBC Production Iron-deficiency anemia

Caused by hemorrhagic anemia, low iron intake, or impaired absorption Microcytic, hypochromic RBCs Iron supplements to treat

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Causes of Anemia: Low RBC Production Pernicious anemia

Autoimmune disease - destroys stomach mucosa Lack of intrinsic factor needed to absorb B12
Deficiency of vitamin B12

RBCs cannot divide macrocytes Treated with B12 injections or nasal gel Also caused by low dietary B12 (vegetarians)

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Causes of Anemia: Low RBC Production Renal anemia

Lack of EPO Often accompanies renal disease Treated with synthetic EPO

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Causes of Anemia: Low RBC Production Aplastic anemia

Destruction or inhibition of red marrow by drugs, chemicals, radiation, viruses Usually cause unknown All cell lines affected
Anemia; clotting and immunity defects

Treated short-term with transfusions; longterm with transplanted stem cells

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Causes of Anemia: High RBC Destruction Hemolytic anemias

Premature RBC lysis Caused by
Hb abnormalities Incompatible transfusions Infections

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Causes of Anemia: High RBC Destruction Usually genetic basis for abnormal Hb Globin abnormal
Fragile RBCs lyse prematurely

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Causes of Anemia: High RBC Destruction Thalassemias

Typically Mediterranean ancestry One globin chain absent or faulty RBCs thin, delicate, deficient in Hb Many subtypes
Severity from mild to severe

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Causes of Anemia: High RBC Destruction Sickle-cell anemia

Hemoglobin S
One amino acid wrong in a globin beta chain

RBCs crescent shaped when unload O2 or blood O2 low RBCs rupture easily and block small vessels
Poor O2 delivery; pain

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Sickle-cell Anemia Black people of African malarial belt and descendants Malaria
Kills 1 million each year

Sickle-cell gene
Two copies Sickle-cell anemia One copy Sickle-cell trait; milder disease; better chance to survive malaria

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Sickle-cell Anemia: Treatments

Acute crisis treated with transfusions; inhaled nitric oxide Preventing sickling
Hydroxyurea induces fetal hemoglobin (which does not sickle) formation Blocking RBC ion channels Stem cell transplants Gene therapy

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Figure 17.8 Sickle-cell anemia.

Val His Leu Thr Pro Glu Glu 1 2 3 4 5 6 7 146 Normal erythrocyte has normal hemoglobin amino acid sequence in the beta chain.

Val His Leu Thr Pro Val Glu 1 2 3 4 5 6 7 146

Sickled erythrocyte results from a single amino acid change in the beta chain of hemoglobin.
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Erythrocyte Disorders Polycythemia vera

Bone marrow cancer excess RBCs Severely increased blood viscosity

Secondary polycythemia
Less O2 available (high altitude) or EPO production increases higher RBC count Blood doping

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Leukocytes Make up <1% of total blood volume

4,800 10,800 WBCs/l blood

Function in defense against disease

Can leave capillaries via diapedesis Move through tissue spaces by ameboid motion and positive chemotaxis

Leukocytosis: WBC count over 11,000/mm3

Normal response to infection
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Leukocytes: Two Categories Granulocytes Visible cytoplasmic granules

Neutrophils, eosinophils, basophils

Agranulocytes No visible cytoplasmic granules

Lymphocytes, monocytes

Decreasing abundance in blood

Never let monkeys eat bananas

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Figure 17.9 Types and relative percentages of leukocytes in normal blood.

Formed elements (not drawn to scale)

Differential WBC count (All total 4800 10,800/ l)

Platelets Granulocytes Neutrophils (5070%) Leukocytes Eosinophils (24%) Basophils (0.51%) Erythrocytes Agranulocytes Lymphocytes (2545%) Monocytes (38%)
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Granulocytes Granulocytes
Larger and shorter-lived than RBCs Lobed nuclei Cytoplasmic granules stain specifically with Wright's stain All phagocytic to some degree

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Neutrophils Most numerous WBCs Also called Polymorphonuclear leukocytes (PMNs or polys) Granules stain lilac; contain hydrolytic enzymes or defensins 3-6 lobes in nucleus; twice size of RBCs Very phagocytic"bacteria slayers"

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Eosinophils Red-staining granules Bilobed nucleus Granules lysosome-like

Release enzymes to digest parasitic worms

Role in allergies and asthma Role in modulating immune response

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Basophils Rarest WBCs Nucleus deep purple with 1-2 constrictions Large, purplish-black (basophilic) granules contain histamine
Histamine: inflammatory chemical that acts as vasodilator to attract WBCs to inflamed sites

Are functionally similar to mast cells

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Figure 17.10a Leukocytes.

Granulocytes

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Neutrophil: Multilobed nucleus, pale red and blue cytoplasmic granules

Figure 17.10b Leukocytes.

Granulocytes

Eosinophil: Bilobed nucleus, red cytoplasmic granules

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Figure 17.10c Leukocytes.

Granulocytes

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Basophil: Bilobed nucleus, purplish-black cytoplasmic granules

Agranulocytes Agranulocytes
Lack visible cytoplasmic granules Have spherical or kidney-shaped nuclei

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Lymphocytes Second most numerous WBC Large, dark-purple, circular nuclei with thin rim of blue cytoplasm Mostly in lymphoid tissue (e.g., lymph nodes, spleen); few circulate in blood Crucial to immunity

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Lymphocytes Two types

T lymphocytes (T cells) act against virusinfected cells and tumor cells B lymphocytes (B cells) give rise to plasma cells, which produce antibodies

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Monocytes Largest leukocytes Abundant pale-blue cytoplasm Dark purple-staining, U- or kidney-shaped nuclei

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Monocytes Leave circulation, enter tissues, and differentiate into macrophages

Actively phagocytic cells; crucial against viruses, intracellular bacterial parasites, and chronic infections

Activate lymphocytes to mount an immune response

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Figure 17.10d Leukocytes.

Agranulocytes

Lymphocyte (small): Large spherical nucleus, thin rim of pale blue cytoplasm
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Figure 17.10e Leukocytes.

Agranulocytes

Monocyte: Kidney-shaped nucleus, abundant pale blue cytoplasm

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Leukopoiesis Production of WBCs

Stimulated by 2 types of chemical messengers from red bone marrow and mature WBCs
Interleukins (e.g., IL-3, IL-5) Colony-stimulating factors (CSFs) named for WBC type they stimulate (e.g., granulocyte-CSF stimulates granulocytes)

All leukocytes originate from hemocytoblasts

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Leukopoiesis Lymphoid stem cells lymphocytes Myeloid stem cells all others Progression of all granulocytes
Myeloblast promyelocyte myelocyte band mature cell

Granulocytes stored in bone marrow 3 times more WBCs produced than RBCs
Shorter life span; die fighting microbes

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Leukopoiesis Progression of agranulocytes differs Monocytes live several months

Share common precursor with neutrophils Monoblast promonocyte monocyte

Lymphocytes live few hours to decades

Lymphoid stem cell T lymphocyte precursors (travel to thymus) and B lymphocyte precursors

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Figure 17.11 Leukocyte formation.

Stem cells Hematopoietic stem cell (hemocytoblast)

Myeloid stem cell

Lymphoid stem cell

Committed cells

Myeloblast

Myeloblast

Myeloblast

Monoblast

B lymphocyte precursor

T lymphocyte precursor

Developmental Promyelocyte pathway

Promyelocyte

Promyelocyte

Promonocyte

Eosinophilic myelocyte

Basophilic myelocyte

Neutrophilic myelocyte

Eosinophilic band cells

Basophilic band cells

Neutrophilic band cells

Granular leukocytes Eosinophils (a) Basophils

Agranular leukocytes Neutrophils (c) Monocytes (d) B lymphocytes T lymphocytes (e) (f)

(b)

Some become

Some become

Some become

Macrophages (tissues) Plasma cells

Effector T cells

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Leukocyte disorders
Leukopenia
Abnormally low WBC countdrug induced

Leukemias all fatal if untreated

Cancer overproduction of abnormal WBCs Named according to abnormal WBC clone involved Myeloid leukemia involves myeloblast descendants Lymphocytic leukemia involves lymphocytes

Acute leukemia derives from stem cells; primarily affects children Chronic leukemia more prevalent in older people
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Leukemia Cancerous leukocytes fill red bone marrow

Other lines crowded out anemia; bleeding

Immature nonfunctional WBCs in bloodstream Death from internal hemorrhage; overwhelming infections Treatments
Irradiation, antileukemic drugs; stem cell transplants
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Infectious Mononucleosis Highly contagious viral disease

Epstein-Barr virus

High numbers atypical agranulocytes Symptoms

Tired, achy, chronic sore throat, low fever

Runs course with rest

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Platelets Cytoplasmic fragments of megakaryocytes Blue-staining outer region; purple granules Granules contain serotonin, Ca2+, enzymes, ADP, and platelet-derived growth factor (PDGF)
Act in clotting process

Normal = 150,000 400,000 platelets /ml of blood

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Platelets Form temporary platelet plug that helps seal breaks in blood vessels Circulating platelets kept inactive and mobile by nitric oxide (NO) and prostacyclin from endothelial cells lining blood vessels Age quickly; degenerate in about 10 days Formation regulated by thrombopoietin Derive from megakaryoblast
Mitosis but no cytokinesis megakaryocyte - large cell with multilobed nucleus
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Figure 17.12 Formation of platelets.

Stem cell

Developmental pathway

Hematopoietic stem cell (hemocytoblast)

Megakaryoblast (stage I megakaryocyte)

Megakaryocyte (stage II/III)

Megakaryocyte (stage IV)

Platelets

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Table 17.2 Summary of Formed Elements of the Blood (1 of 2)

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Table 17.2 Summary of Formed Elements of the Blood (2 of 2)

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Hemostasis Fast series of reactions for stoppage of bleeding Requires clotting factors, and substances released by platelets and injured tissues Three steps
1. Vascular spasm 2. Platelet plug formation 3. Coagulation (blood clotting)
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Hemostasis: Vascular Spasm Vasoconstriction of damaged blood vessel Triggers

Direct injury to vascular smooth muscle Chemicals released by endothelial cells and platelets Pain reflexes

Most effective in smaller blood vessels

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Hemostasis: Platelet Plug Formation Positive feedback cycle Damaged endothelium exposes collagen fibers
Platelets stick to collagen fibers via plasma protein von Willebrand factor Swell, become spiked and sticky, and release chemical messengers
ADP causes more platelets to stick and release their contents Serotonin and thromboxane A2 enhance vascular spasm and platelet aggregation

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Hemostasis: Coagulation Reinforces platelet plug with fibrin threads Blood transformed from liquid to gel Series of reactions using clotting factors (procoagulants)
# I XIII; most plasma proteins Vitamin K needed to synthesize 4 of them

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Figure 17.13 Events of hemostasis.

Slide 1

Step 1 Vascular spasm Smooth muscle contracts, causing vasoconstriction.

Collagen fibers

Step 2 Platelet plug formation Injury to lining of vessel exposes collagen fibers; platelets adhere. Platelets release chemicals that make nearby platelets sticky; platelet plug forms.

Platelets

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Fibrin

Step 3 Coagulation Fibrin forms a mesh that traps red blood cells and platelets, forming the clot.

Coagulation: Overview Three phases of coagulation

Prothrombin activator formed in both intrinsic and extrinsic pathways Prothrombin converted to enzyme thrombin Thrombin catalyzes fibrinogen fibrin

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Coagulation Phase 1: Two Pathways to Prothrombin Activator Initiated by either intrinsic or extrinsic pathway (usually both)
Triggered by tissue-damaging events Involves a series of procoagulants Each pathway cascades toward factor X

Factor X complexes with Ca2+, PF3, and factor V to form prothrombin activator

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Coagulation Phase 1: Two Pathways to Prothrombin Activator Intrinsic pathway

Triggered by negatively charged surfaces (activated platelets, collagen, glass) Uses factors present within blood (intrinsic)

Extrinsic pathway
Triggered by exposure to tissue factor (TF) or factor III (an extrinsic factor) Bypasses several steps of intrinsic pathway, so faster

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Coagulation Phase 2: Pathway to Thrombin Prothrombin activator catalyzes transformation of prothrombin to active enzyme thrombin Once prothrombin activator formed, clot forms in 1015 seconds

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Coagulation Phase 3: Common Pathway to the Fibrin Mesh Thrombin converts soluble fibrinogen to fibrin Fibrin strands form structural basis of clot Fibrin causes plasma to become a gel-like trap for formed elements Thrombin (with Ca2+) activates factor XIII which:
Cross-links fibrin Strengthens and stabilizes clot
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Figure 17.14 The intrinsic and extrinsic pathways of blood clotting (coagulation). (1 of 2)

Phase 1
Intrinsic pathway Vessel endothelium ruptures, exposing underlying tissues (e.g., collagen) Platelets cling and their surfaces provide sites for mobilization of factors XII Ca2+ XIIa XI XIa VIIa IX IXa PF3 released by aggregated platelets Ca2+ VII Extrinsic pathway Tissue cell trauma exposes blood to

Tissue factor (TF)

VIII

VIIIa
IXa/VIIIa complex X Xa Ca2+ PF3 Prothrombin activator
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TF/VIIa complex

Va

Figure 17.14 The intrinsic and extrinsic pathways of blood clotting (coagulation). (2 of 2)

Phase 2
Prothrombin (II) Thrombin (IIa)

Phase 3
Fibrinogen (I) (soluble) Fibrin (insoluble polymer) XIIIa Cross-linked fibrin mesh
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Ca2+
XIII

Figure 17.15 Scanning electron micrograph of erythrocytes trapped in a fibrin mesh.

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Clot Retraction Stabilizes clot Actin and myosin in platelets contract within 3060 minutes Contraction pulls on fibrin strands, squeezing serum from clot Draws ruptured blood vessel edges together

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Vessel Repair Vessel is healing as clot retraction occurs Platelet-derived growth factor (PDGF) stimulates division of smooth muscle cells and fibroblasts to rebuild blood vessel wall Vascular endothelial growth factor (VEGF) stimulates endothelial cells to multiply and restore endothelial lining

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Fibrinolysis Removes unneeded clots after healing Begins within two days; continues for several Plasminogen in clot is converted to plasmin by tissue plasminogen activator (tPA), factor XII and thrombin Plasmin is a fibrin-digesting enzyme

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Factors Limiting Clot Growth or Formation Two mechanisms limit clot size
Swift removal and dilution of clotting factors Inhibition of activated clotting factors

Thrombin bound onto fibrin threads Antithrombin III inactivates unbound thrombin Heparin in basophil and mast cells inhibits thrombin by enhancing antithrombin III

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Factors Preventing Undesirable Clotting Platelet adhesion is prevented by

Smooth endothelium of blood vessels prevents platelets from clinging Antithrombic substances nitric oxide and prostacyclin secreted by endothelial cells Vitamin E quinone acts as potent anticoagulant

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Disorders of Hemostasis Thromboembolic disorders: undesirable clot formation Bleeding disorders: abnormalities that prevent normal clot formation Disseminated intravascular coagulation (DIC)
Involves both types of disorders

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Thromboembolic Conditions Thrombus: clot that develops and persists in unbroken blood vessel
May block circulation leading to tissue death

Embolus: thrombus freely floating in bloodstream Embolism: embolus obstructing a vessel

E.g., pulmonary and cerebral emboli

Risk factors atherosclerosis, inflammation, slowly flowing blood or blood stasis from immobility
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Anticoagulant Drugs Aspirin

Antiprostaglandin that inhibits thromboxane A2

Heparin
Anticoagulant used clinically for pre- and postoperative cardiac care

Warfarin (Coumadin)
Used for those prone to atrial fibrillation Interferes with action of vitamin K

Dabigatran directly inhibits thrombin

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Bleeding Disorders Thrombocytopenia: deficient number of circulating platelets

Petechiae appear due to spontaneous, widespread hemorrhage Due to suppression or destruction of red bone marrow (e.g., malignancy, radiation, drugs) Platelet count <50,000/l is diagnostic Treated with transfusion of concentrated platelets

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Bleeding Disorders Impaired liver function

Inability to synthesize procoagulants Causes include vitamin K deficiency, hepatitis, and cirrhosis Impaired fat absorption and liver disease can also prevent liver from producing bile, impairing fat and vitamin K absorption

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Bleeding Disorders
Hemophilia includes several similar hereditary bleeding disorders
Hemophilia A: most common type (77% of all cases); factor VIII deficiency Hemophilia B: factor IX deficiency Hemophilia C: mild type; factor XI deficiency

Symptoms include prolonged bleeding, especially into joint cavities Treated with plasma transfusions and injection of missing factors
Increased hepatitis and HIV risk
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Disseminated Intravascular Coagulation (DIC) Clotting causes bleeding

Widespread clotting blocks intact blood vessels Severe bleeding occurs because residual blood unable to clot

Occurs as pregnancy complication; in septicemia, or incompatible blood transfusions

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Transfusions Whole-blood transfusions used when blood loss rapid and substantial Packed red cells (plasma and WBCs removed) transfused to restore oxygencarrying capacity Transfusion of incompatible blood can be fatal

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Human Blood Groups

RBC membranes bear 30 types of glycoprotein antigens
Anything perceived as foreign; generates an immune response Promoters of agglutination; called agglutinogens

Mismatched transfused blood perceived as foreign

May be agglutinated and destroyed; can be fatal

Presence or absence of each antigen is used to classify blood cells into different groups

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Blood Groups Antigens of ABO and Rh blood groups cause vigorous transfusion reactions Other blood groups (MNS, Duffy, Kell, and Lewis) usually weak agglutinogens

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ABO Blood Groups Types A, B, AB, and O Based on presence or absence of two agglutinogens (A and B) on surface of RBCs Blood may contain preformed anti-A or anti-B antibodies (agglutinins)
Act against transfused RBCs with ABO antigens not present on recipient's RBCs

Anti-A or anti-B form in blood at about 2 months of age; adult levels by 8-10
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Table 17.4 ABO Blood Groups

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Rh Blood Groups 52 named Rh agglutinogens (Rh factors) C, D, and E are most common Rh+ indicates presence of D antigen
85% Americans Rh+

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Rh Blood Groups Anti-Rh antibodies not spontaneously formed in Rh individuals

Anti-Rh antibodies form if Rh individual receives Rh+ blood, or Rh mom carrying Rh+ fetus

Second exposure to Rh+ blood will result in typical transfusion reaction

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Homeostatic Imbalance: Hemolytic Disease of the Newborn Also called erythroblastosis fetalis
Only occurs in Rh mom with Rh+ fetus

Rh mom exposed to Rh+ blood of fetus during delivery of first baby baby healthy
Mother synthesizes anti-Rh antibodies

Second pregnancy
Mom's anti-Rh antibodies cross placenta and destroy RBCs of Rh+ baby

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Homeostatic Imbalance: Hemolytic Disease of the Newborn Baby treated with prebirth transfusions and exchange transfusions after birth RhoGAM serum containing anti-Rh can prevent Rh mother from becoming sensitized

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Transfusion Reactions Occur if mismatched blood infused Donor's cells

Attacked by recipient's plasma agglutinins Agglutinate and clog small vessels Rupture and release hemoglobin into bloodstream

Result in
Diminished oxygen-carrying capacity Diminished blood flow beyond blocked vessels Hemoglobin in kidney tubules renal failure
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Transfusion Reactions Symptoms

Fever, chills, low blood pressure, rapid heartbeat, nausea, vomiting

Treatment
Preventing kidney damage
Fluids and diuretics to wash out hemoglobin

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Transfusions Type O universal donor

No A or B antigens

Type AB universal recipient

No anti-A or anti-B antibodies

Misleading - other agglutinogens cause transfusion reactions Autologous transfusions

Patient predonates

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