Blood

BLOOD

CIRCULATORY SYSTEM
* BLOOD
* HEART
* BLOOD VESSELS

FUNCTIONS OF BLOOD
* TRANSPORT
* PROTECTION
* REGULATION

TRANSPORT
* OXYGEN (O2)
* CARBON DIOXIDE (CO2)
* NUTRIENTS
* WASTES
* HORMONES
PROTECTION
* IMMUNE SYSTEM
o WHITE BLOOD CELLS
o ANTIBODIES
* CLOTTING SYSTEM
o PLATELETS
o FIBRINOGEN / FIBRIN

REGULATION
* BODY TEMPERATURE
* pH
* WATER BALANCE
* ELECTROLYTE BALANCE

BLOOD COMPOSITION
BLOOD IS COMPRISED OF TWO MAIN COMPONENTS:
* PLASMA
* FORMED ELEMENTS
THESE COMPONENTS CAN BE SEPARATED BY CENTRIFUGATION
THE FRACTION OF THE BLOOD VOLUME COMPRISED OF RED BLOOD CELLS IS TERMED THE HEMATOCRIT

PLASMA COMPOSITION
* WATER (~90%)
* SOLUTES (~10%)
o PROTEINS (~8%)
o OTHER COMPOUNDS (~2%)
+ NUTRIENTS
+ GASES
+ WASTES
+ HORMONES
+ ELECTROLYTES

PLASMA PROTEINS
* MOST ABUNDANT PLASMA SOLUTE
* LIVER CAN PRODUCE 4 GRAMS OF PLASMA PROTEINS PER HOUR
* THREE MAJOR CATEGORIES
o ALBUMINS
o GLOBULINS
o FIBRINOGEN
ALBUMINS
* ~60% OF PLASMA PROTEINS
* SMALL
* TRANSPORT LIPIDS, HORMONES, CALCIUM, ETC.
* BUFFER BLOOD pH
* CONTRIBUTE TO VISCOSITY & OSMOLARITY
* INFLUENCE BLOOD PRESSURE, BLOOD FLOW, AND FLUID BALANCE

GLOBULINS
* ~36% OF PLASMA PROTEINS
* THREE SUBCLASSES
o ALPHA (a)
o BETA (b)
o GAMMA (g)
* ALPHA (a)
o VARIOUS FUNCTIONS, ESPECIALLY TRANSPORT
* BETA (b)
o VARIOUS FUNCTIONS, ESPECIALLY TRANSPORT
* GAMMA (g)
o COMPONENTS OF IMMUNE SYSTEM
o PRODUCED BY PLASMA CELLS, WHICH ARE DESCENDED FROM WHITE BLOOD CELLS

FIBRINOGEN
* ~4% OF PLASMA PROTEINS
* PRECURSOR OF FIBRIN
* INVOLVED IN BLOOD CLOTTING

PLASMA: NUTRIENTS
* SUGARS
* AMINO ACIDS
* FATS
* CHOLESTEROL
* PHOSPHOLIPIDS
* VITAMINS
* MINERALS

PLASMA: GASES
* OXYGEN (O2)
o REQUIRED FOR CELLULAR RESPIRATION
* CARBON DIOXIDE (CO2)
o PRODUCT OF CELLULAR RESPIRATION
* NITROGEN (N2)
o USUALLY PHYSIOLOGICALLY UNIMPORTANT
o WHY DO YOU THINK IT IS THERE?

PLASMA: WASTES
NITROGENOUS WASTES
* PRODUCTS OF CATABOLISM
o (ESP: AMINO ACID CATABOLISM)
* MOST ABUNDANT IS UREA
* REMOVED FROM BLOOD BY KIDNEYS
* EXCRETED THROUGH URINE
* RATE OF REMOVAL BALANCES RATE OF PRODUCTION

PLASMA: ELECTROLYTES
* SODIUM (Na+)
* CALCIUM (Ca2+)
* POTASSIUM (K+)
* MAGNESIUM (Mg2+)
* CHLORIDE (Cl-)
* BICARBONATE (HCO3-)
* PHOSPHATE (HPO42-)
* SULFATE (SO42-)
* VARIOUS IONS
* SODIUM IS THE MOST PREVALENT
* INCREASE BLOOD OSMOLARITY
o AFFECT BLOOD VOLUME
o AFFECT BLOOD PRESSURE

FORMED ELEMENTS
* ERYTHROCYTES (RED BLOOD CELLS)
* LEUKOCYTES (WHITE BLOOD CELLS)
* PLATELETS (CELL FRAGMENTS)

ERYTHROCYTE FUNCTIONS
* CARRY O2 FROM LUNGS TO CELLS
* CARRY CO2 FROM CELLS TO LUNGS
* HOW DO O2 AND CO2 RELATE TO THE FUNCTIONS OF A CELL?

ERYTHROCYTE QUANTITIES
* MEN: 4.6 – 6.2 MILLION/mL IN
o HEMATOCRIT 42 – 52 (% RBCs)
* WOMEN: 4.2 – 5.4 MILLION/mL
o HEMATOCRIT 37 – 48 (% RBCs)
* GENDER DIFFERENCES BASED ON:
o ANDROGENS INCREASE NUMBER
o MENSTRUAL LOSS DECREASES NUMBER
o BODY FAT (INVERSE RELATIONSHIP)
o FASTER CLOTTING IN MEN

ERYTHROCYTE STRUCTURE
* DISC SHAPED
* BICONCAVE
* 7.5 MICROMETER (mm) DIAMETER
* 2 MICROMETERS (mm) THICK

ERYTHROCYTE STRUCTURE
PLASMA MEMBRANE
* PHOSPHOLIPID BILAYER
* GLYCOPROTEINS, GLYCOLIPIDS
o DETERMINE BLOOD TYPE
* ACTIN AND SPECTRIN ON INNER SURFACE
o RESILIENCE / DURABILITY / PLIABILITY
* HIGH SURFACE AREA:VOLUME RATIO
o RESULT OF BICONCAVE SHAPE
o INCREASES RATE OF GAS DIFFUSION INTO AND OUT OF CELLS

ERYTHROCYTE STRUCTURE
CYTOPLASM
* LACKS ORGANELLES
o ESP: LACKS MITOCHONDRIA, NUCLEUS
o WHY IS THIS IMPORTANT?
o CANNOT REPAIR
o LIMITED LIFESPAN (~120 DAYS)
o CANNOT DIVIDE
o NEW CELLS FORMED IN BONE MARROW
* HEMOGLOBIN
o RED PIGMENT
o HIGH CONCENTRATION (33%)
o 280 MILLION MOLECULES PER CELL
o CARRIES MOST OF THE O2
o CARRIES SOME OF THE CO2
o PROTEIN & NON-PROTEIN COMPONENTS

HEMOGLOBIN
PROTEIN COMPONENT
* 4 POLYPEPTIDES (HETEROTETRAMER)
o 2 a-GLOBIN PROTEINS
o 2 b-GLOBIN PROTEINS
NON-PROTEIN COMPONENT
* 4 HEME GROUPS
o PORPHYRIN RING AND IRON ION
o IRON ION WITHIN HEME BINDS TO O2

ABO BLOOD TYPES
* DETERMINED BY SURFACE ANTIGENS
o GLYCOLIPIDS AND GLCOPROTEINS
+ (SUGARS ON CELL SURFACE)
o GENETICALLY DETERMINED
o RECOGNIZED BY ANTIBODIES
o INDIVIDUALS POSSESS ANTIBODIES TO ANTIGENS THEY THEMSELVES DO NOT POSSESS
o RECOGNITION OF THESE ANTIGENS BY ANTIBODIES CAUSES CELL CLUMPING
* DETERMINED BY GENE “I”
* THREE ALLELES
o IA
o IB
o i
* IA AND IB ARE CODOMINANT
* i IS RECESSIVE TO IA AND IB
* THREE ALLELES OF “I” GENE
* INDIVIDUALS POSSESS TWO COPIES
* FOUR BLOOD TYPES
o A GENOTYPE IAIA OR IAi
o B GENOTYPE IBIB OR IBi
o AB GENOTYPE IAIB
o O GENOTYPE ii

ANTIBODIES TO A AND B ANTIGENS
* APPEAR SHORTLY AFTER BIRTH
* PRESENT FOR ENTIRE LIFE
* PRODUCED IN RESPONSE TO SIMILAR ANTIGENS ON INTESTINAL BACTERIA
* CROSS-REACT WITH A AND B ANTIGENS
* TERMED “ANTI-A” AND “ANTI-B”
* CAUSE OF TRANSFUSION REACTIONS

Rh BLOOD TYPES
* DETERMINED BY SURFACE ANTIGENS
* UNRELATED TO ABO BLOOD TYPE
* GENETICALLY DETERMINED
* ALLELES OF THREE GENES
o C, c, D, d, E, e
o DD, Dd ARE Rh+
o dd MAY BE Rh-, DEPENDING ON ALLELES OF OTHER GENES
* ANTI-D ANTIBODIES NOT NORMALLY PRESENT
o PRESENT ONLY IN Rh- EXPOSED TO Rh+
o FIRST EXPOSURE NOT PROBLEMATIC
o SECOND EXPOSURE PROBLEMATIC
o TRANSFUSION / PREGNANCY
* IMMUNE RESPONSE PREVENTABLE
o RhoGAM (Rh IMMUNE GLOBULIN)

OTHER BLOOD GROUPS
* > 100 OTHER BLOOD GROUPS
* USEFUL IN GENETIC / BIOCHEMICAL TESTING
* RARELY CAUSE TRANSFUSION REACTIONS

ERYTHROCYTE DISORDERS
ANEMIA
* ERYTHROCYTE DEFICIENCY, OR
* HEMOGLOBIN DEFICIENCY
* THREE CLASSES
o INADEQUATE SYNTHESIS
o BLEEDING
o RBC DESTRUCTION
* CONSEQUENCES
o OXYGEN DEPRIVATION (HYPOXIA)
+ SHORTNESS OF BREATH
o REDUCED BLOOD OSMOLARITY
+ WATER RETENTION IN TISSUES (EDEMA)
o REDUCED BLOOD VISCOSITY
+ HEART BEATS FASTER
+ CARDIAC FAILURE
SICKLE-CELL ANEMIA
* ~0.25% OF AFRICAN AMERICANS
* GENETICALLY DETERMINED
* ABERRANT b-GLOBIN ALLELE (HbS)
o SINGLE AMINO ACID SUBSTITUTION
o GLUTAMIC ACID (HbA)  VALINE (HbS)
* CELLS SICKLE UNDER LOW OXYGEN
* MULTIPLE DELETERIOUS EFFECTS

* WHY IS THE FREQUENCY SO HIGH?
o MALARIA PREVALENT IN AFRICA
o Plasmodium PARASITE LIVES IN RBCs
o SURVIVES POORLY IN CELLS WITH HbS
o INDIVIDUALS WITH HbS LESS LIKELY TO DIE (HETEROZYGOTES MOST FIT)
o THUS, HbS PROVIDES PROTECTION

LEUKOCYTES
* 5,000 – 10,000 CELLS/mL
* FIVE TYPES:
o NEUTROPHILS 60 – 70 % 9 – 12 mM
o LYMPHOCYTES 25 – 33% 5 – 8 mM (most)
o MONOCYTES 3 – 8 % 12 – 15 mM
o EOSINOPHILS 2 – 4% 10 – 14 mM
o BASOPHILS <0.5 – 1% 8 – 10 mM
* GRANULOCYTES
o NEUTROPHILS
o EOSINOPHILS
o BASOPHILS
* AGRANULOCYTES
o LYMPHOCYTES
o MONOCYTES
LEUKOCYTES
NEUTROPHILS
* HIGHLY MOBILE
* INCREASE IN RESPONSE TO BACTERIAL INFECTIONS
* KILLS BACTERIA
o PHAGOCYTOSIS
o CHEMICALLY (BURST LYSOSOMES)

EOSINOPHILS
* INCREASE WITH ALLERGIES
* INCREASE WITH PARASITIC INFECTIONS
* PHAGOCYTOSIS
o ANTIGEN / ANTIBODY COMPLEXES
o ALLERGENS
* HYDROLYTIC ENZYME RELEASE
o RESPONSE TO HOOKWORM, TAPEWORM, ETC.
o TOO LARGE TO PHAGOCYTIZE
BASOPHILS
* GENERALLY NOT PHAGOCYTIC
* AID OTHER LEUKOCYTES
o RELEASE HISTAMINE
+ INCREASE BLOOD FLOW TO AREA
o RELEASE HEPARIN
+ INHIBIT CLOTTING
LYMPHOCYTES
* INCREASE IN IMMUNE RESPONSE
* SEVERAL SUBCLASSES
* VARIOUS IMMUNE FUNCTIONS
o ESP: SECRETE ANTIBODIES

MONOCYTES
* DIFFERENTIATE INTO MACROPHAGES
* PHAGOCYTOSIS OF PATHOGENS
* PHAGOCYTOSIS OF DEBRIS
* PRESENT ANTIGENS TO OTHER CELLS OF IMMUNE SYSTEM
PLATELETS
* 130,000 – 400,000 / mL
* NOT CELLS
o FRAGMENTS OF MEGAKARYOCYTES
o SMALL (2 – 4 mM DIAMETER)
* POSSESS VARIOUS ORGANELLES
* PSEUDOPODS
o AMOEBOID MOVEMENT
o PHAGOCYTOSIS
PLATELET FUNCTIONS
* SECRETE CLOTTING FACTORS
* SECRETE VASOCONSTRICTORS
* FORM TEMPORARY PLATELET PLUGS
* DISSOLVE OLD BLOOD CLOTS
* PHAGOCYTOSIS OF BACTERIA
* SECRETE CHEMICALS TO ATTRACT LEUKOCYTES TO SITES OF INFLAMMATION
* SECRETE GROWTH FACTORS

CONTROL OF BLEEDING
HEMOSTASIS
* VASCULAR SPASM
* PLATELET PLUG FORMATION
* COAGULATION
VASCULAR SPASM
* CONSTRICTION OF BROKEN VESSEL
* IMMEDIATE PROTECTION AGAINST BLEEDING
* MULTIPLE TRIGGERS
TRIGGERS OF VASCULAR SPASM
* PAIN RECEPTORS  NERVES  BLOOD VESSELS CONSTRICT
* SMOOTH MUSCLE OF BLOOD VESSELS CONSTRICT
* PLATELETS RELEASE SEROTONIN (CHEMICAL VASOCONSTRICTOR)
PLATELET PLUG FORMATION
* BLOOD VESSEL BROKEN
* COLLAGEN FIBERS EXPOSED
* PLATELETS BIND TO COLLAGE FIBERS
o FORM PSEUDOPODS
o ATTACH TO VESSEL AND OTHER PLATELETS
o CONTRACT AND PULL WALLS TOGETHER
o DEGRANULATION
PLATELET PLUG FORMATION
* DEGRANULATION
o RELEASE OF COMPOUNDS TO
+ VASOCONSTRICT
+ ATTRACT PLATELETS
+ STIMULATE DEGRANULATION
+ PROMOTE AGGREGATION
o POSITIVE FEEDBACK
CONTROL OF BLEEDING
* COAGULATION (CLOTTING)
* MOST EFFECTIVE DEFENSE
* FIBRINOGEN  FIBRIN  POLYMER
* TWO REACTION PATHWAYS
o EXTRINSIC MECHANISM
+ CLOTTING FACTORS FROM DAMAGED BLOOD VESSEL
o INTRINSIC MECHANISM
+ CLOTTING FACTORS FROM BLOOD
CLOTTING FACTORS
* PROCOAGULANTS
* PROTEINS PRODUCED IN LIVER
* INACTIVE  ACTIVE
o EACH ACTIVATES THE NEXT
o REACTION CASCADE
o AMPLIFICATION AT EACH STEP
o POSITIVE FEEDBACK INVOLVED
* CLOT RETRACTION
o CLOT FORMED
o PLATELETS ADHERE TO FIBRIN
o PLATELETS CONTRACT
o PULLS EDGES OF BROKEN VESSEL TOGETHER
* PLATELETS SECRETE PDGF
o PLATELET-DERIVED GROWTH FACTOR
o STIMULATES MITOSIS
* FIBROBLASTS INVADE AND PRODUCE CONNECTIVE TISSUE

CLOT DISSOLUTION
* FIBRINOLYSIS
* MULTIPLE STEPS
* POSITIVE FEEDBACK
* SIMILAR, IN REVERSE
PREVENTION OF COAGULATION
* PLATELET REPULSION
* DILUTION AND BLOOD MOVEMENT
* ANTICOAGULANTS
o ANTITHROMBIN (LIVER)
o HEPARIN (BASOPHILS)

COAGULATION DISORDERS
HEMOPHILIA

* DEFICIENCY IN A CLOTTING FACTOR
* CASCADE DISRUPTED
* CLOTTING DEFICIENCY
COAGULATION DISORDERS
HEMOPHILIA A
COAGULATION DISORDERS
HEMOPHILIA B
BLOOD CELL PRODUCTION
STEM CELLS
* PLURIPOTENT CELLS
o UNDIFFERENTIATED CELLS
o ABLE TO DIVIDE AND DIFFERENTIATE INTO MULTIPLE TYPES OF CELLS
o NOT ALL ARE “TOTIPOTENT”
o (NOT FULLY DIFFERENTIATED)
o E.G., HEMOCYTOBLASTS (BLOOD)
o E.G., EMBRYONIC STEM CELLS
* YOLK SAC
o EARLIEST HEMOPOIETIC TISSUE
o PRODUCES STEM CELLS
o COLONIZE OTHER ORGANS
+ BONE, LIVER, SPLEEN, THYMUS, ETC
o LIVER STOPS HEMOPOIESIS AT BIRTH
o SPLEEN STOPS ERYTHROPOIESIS SHORTLY AFTER BIRTH
* MYELOID HEMOPOIESIS
o OCCURS IN BONE MARROW
o FORMS ALL SEVEN FORMED ELEMENTS
* LYMPHOID HEMOPOIESIS
o OCCURS IN SEVERAL ORGANS
+ THYMUS, TONSILS, LYMPH NODES, SPLEEN, INTESTINES, ETC.
o PRODUCES LYMPHOCYTES
HEMOCYTOBLASTS
* STEM CELLS
* PLURIPOTENT
* DIFFERENTIATE INTO ALL FORMED ELEMENTS
o ERYTHROPOIESIS
o LEUKOPOIESIS
o THROMBOPOIESIS

ERYTHROCYTE PRODUCTION
ERYTHROPOIESIS
ERYTHROCYTE PRODUCTION
ERYTHROPOIESIS
ERYTHROCYTE HOMEOSTASIS
IRON METABOLISM
ERYTHROCYTE DEATH
HEMOLYSIS
* IRON
* PORPHYRIN RING
LEUKOCYTE PRODUCTION
LEUKOPOIESIS
PLATELET PRODUCTION
THROMBOPOIESIS
PLATELET PRODUCTION

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