Chapter 19 - Blood

Functions of Blood Transportation

Delivery of nutrients, hormones Removal of wastes

Regulation Body temperature pH Fluid volume

Protection Prevent blood loss Prevent infection

Physical Characteristics of Blood A liquid connective tissue A mixture

Formed elements - living blood cells Plasma - fluid matrix

Heavier, thicker, more viscous than water Due to ions, plasma proteins, blood cells Composition and volume regulated by hormones

Temp - 38° C, higher than body temperature pH - 7.4 (ranges from 7.35-7.45) Volume differs between sexes, conditional

Female - average 4-5 L Male - average 5-6 L

Components of Blood

Blood sample Spin it Separates into 2 parts

plasma • straw colored liquid on top• 55% of the volume

formed elements • solid portion on bottom

– red blood cells– buffy coat - white blood cells and platelets

45% of the volume Hematocrit

percentage of formed element in a volume of blood about 45% (higher in males than females)

Components of Blood

Blood Plasma Plasma

92% water 7% proteins 1% other solutes

Proteins important (I ) for osmotic balance Albumin Fibrinogen (blood

clotting) Globulins Regulatory

proteins

Blood Plasma

Other solutes Waste products Nutrients Regulatory

substances Gases Electrolytes

Blood Plasma

Formed elements 99% red blood cells 1% white blood cells

and thrombocytes (platelets)

Formed Elements

Erythrocytes - Red Blood Cell's (RBC’s)

IMPORTANT! Note the differences in relative size and appearance!

Formed Elements

Leukocytes - White Blood Cells Granular

leukocytes (granulocytes)

neutrophils eosinophils basophils

Agranular leukocytes (agranulocytes)

lymphocytes - T cells, B cells

Monocytes Thrombocytes -

platelets

Formed Elements

Blood Components

Hematopoiesis - blood cell formation All blood cells come from pluripotent hematopoietic

stem cells (hemocytoblasts) Reside in red bone marrow Give rise to precursor cells which develop into RBC’s,

WBC’s and thrombocytes

Formation of Blood Cells

Formation of Blood Cells

Erythropoiesis RBC production, specifically Hormonally controlled Three phases

production of ribosomes synthesis of hemoglobin ejection of the nucleus and organelles

Leave bone marrow as reticulocyte Mature in blood to a erythrocyte

Regulation of RBC production Regulated by negative feedback

O2 levels monitored in kidneys hypoxia increases RBC production

Production stimulated by erythropoietin (EPO) from kidneys Numbers

M - 5.4 million RBC’s/L (Testosterone stimulates EPO) F - 4.8 million RBC's/L 2 million cells released into blood/second

Anemia - Low O2 carrying capacity of blood Insufficient # of RBC’s

hemorrhage - loss of RBC’s hemolytic anemia - premature RBC rupture due to transfusion,

disease, genetic problems aplastic anemia

• destruction or inhibition of hematopoietic components in bond marrow

• toxins, drugs or irradiation Decreased hemoglobin content

iron (heme) deficiency insufficient iron due to diet or poor absorption

Formation of Blood Cells

Hematocrit % of blood that is RBC’s M 40-54% (47%), F 38-46% (42%), Why? Indicates RBC production and hydration

state Abnormal Hct?

altitude – hypoxia, increased RBC’s athletes - blood doping anemia – decreased RBC’s dehydration

Formation of Blood Cells

Red Blood Cells (Erythrocytes) RBC’s

99% of formed elements

Function to carry O2 Anatomy

Biconcave disks, 8µm in diameter

No nucleus or metabolic machinery

Filled with hemoglobin (Hgb)

O2 carrying protein synthesized in

cytosol before nucleus lost

33% of cell weight

Red Blood Cells (Erythrocytes) Normal Hgb in blood

Infants 14-20g Hgb/100ml

Adult Male 14-15g Hgb

/100ml Female 12-15g

Hgb /100 ml 1.3 ml O2/g Hgb

RBC’s (Light Microscopy)

RBC Physiology RBC specialized for O2

carrying 280 million Hgb

molecules/cell All internal space

available for O2 carrying - no metabolism

Concave shape Allows higher surface

area/volume ratio increases gas diffusion

Allows passage through capillaries, very flexible

RBC Physiology

RBC Physiology

O2 combines with Hgb in lungs O2 not very soluble in H2O Need something to carry it

Hemoglobin 4 globin (protein) chains - 2 chains, 2 chains 4 non-protein heme pigments Heme pigment has iron ion (Fe²+) that carries 1 O2

Each RBC can carry about 1 billion O2 molecules RBC's carry ¼ CO2 bound to hgb - forms

carbaminohemoglobin

RBC Life Cycle Life span

Only 100-120 days Cells cannot repair damage due to loss of nucleus,

ribosomes Old RBC’s destroyed in liver, spleen

Macrophages eat old RBC's Breakdown products recycled Different pathways for each part of Hgb molecule

globin - AA's used for other protein synthesis heme

• iron portion - Fe2+ recycled• non-iron portion - bilirubin

– released in bile, secreted into blood– bile enters intestine converted to urobilinogen by

bacteria– gives urine/feces color

RBC Life Cycle

Granular Leukocytes

Neutrophil

Eosinophil

Basophil

Neutrophil 60-70% of all WBC’s Anatomy

10-12 µm diameter 2-5 connected nuclear

lobes Fine, pale lilac granules

Physiology Respond first to bacteria

damage by chemotaxis Phagocytosis After engulfing pathogen

release several chemicals

lysozymes strong oxidants defensins

Eosinophil 2-4% of all WBC’s Anatomy

10-12 µm diameter 2-3 connected

nuclear lobes red/orange large,

uniform granules, do not block nucleus

Physiology Exit capillaries, enter

tissue fluid Combat

parasites histamine

Phagocytize antigen-antibody complexes

Basophil 0.5-1% of all WBC’s Anatomy

8-10 µm diameter Bilobed nucleus Large granules round,

blue-black, block nucleus

Physiology Exit caps enter tissue

fluids Release heparin,

histamine, serotonin – stimulate inflammation

Hypersensitivity (allergic) reactions

Agranular Leukocytes

Lymphocyte

Monocyte

Lymphocytes

20-25% of all WBC’s

Anatomy 7-15µm Nucleus dark

stained, round or indented

Cytoplasm sky blue rim around nucleus

Lymphocytes - Physiology

Immune response through lymphocytes responding to antigen

An antigen is: Any chemical substance recognized as foreign

when in body Substance (mainly proteins) that stimulate

immune response

Lymphocytes - Physiology

Two types of lymphocytes B-cells

particularly active in killing bacteria develop into plasma cells to form antibodies

• antigen blockers that create antibody-antigen complex

• complex prevents interactions w/ other body cells

T-cells kill viruses, fungi, transplants, cancer, some

bacteria 3 types of cells

• cytotoxic (killer) T cells - destroy foreign invaders • helper T cells - assist B cells and cytotoxic T cells• memory T cells - immune response memory

Monocytes 3-8% of all WBC’s Anatomy

12-20 µm Indented or kidney-

shaped nucleus (not smooth)

cytoplasm foamy Physiology

Slow to respond but arrive in larger numbers

Enlarge, differentiate into wandering macrophages

Clean up cellular debris, microbes following infection

Leukocyte Life Span and Number Life span determined by foreign invaders!

Ingesting foreign bodies toxic, shortens cell life Healthy WBC's - months/years, generally days During infection may only live hours

fill with toxins may die or burst

Leukocyte Life Span and Number 5,000 - 10,000 WBC’s/mm3 blood

RBC/WBC ratio 700/1 Differential WBC count (We have seen these

before!) Neutrophils 60-70% Lymphocytes 20-25% Monocytes 3-8% Eosinophils 2-4% Basophils 0.5-1%

Leukocyte Disorders Leukopenia

Insufficient WBC production Induced by drugs - glucocorticoids, anti-cancer

drugs Leukemia

Cancer (excess production) of the leukocytes Bone marrow fills with cancerous

(nonfunctional) leukocytes Crowds out other cells types

anemia bleeding

Leukocyte Disorders Generally a

descendent of a single cell Different types of

cells myelocytic

leukemia lymphocytic

leukemia Under different

cancerous conditions acute - if derived

from -blast type cells

chronic - if derived from later stages

1.

2.3.

4.

5.Answers

1. Neutrophil2. Basophil3. Monocyte4. Lymphocyte5. Eosinophil

QUIZ!Identify themarked cells!

Platelets - Thrombocytes Development

Megakaryoblasts shed small fragments

Each fragment has plasma membrane

Anatomy 250,000-

400,000/mm3

No nucleus, disc shaped

2-4 µm diameter w/ many granules

Platelets Physiology

Short life span (5-9 days)

Help plug small holes in vessels

Granules several important functions

alpha granules• clotting factors• platelet derived

growth factor (PDGF)

dense granules - Ca++, ADP, ATP, etc.

Also Thromboxane A2, vasoconstrictors, clot promoting enzymes

Hemostasis

3 mechanisms in stopping bleeding

First - Vascular Spasm Blood vessel constricts when damaged

wall smooth muscle contracts immediately slows flow through vessel reflexive?

Hemostasis Second - Platelet Plug

Formation1) Platelet adhesion

platelets stick to exposed collagen activates platelets

2) Platelet release reaction platelets attach to other platelets release granule contents

(thromboxane A2) promote vasoconstriction, platelet

activation and aggregation

3) Platelet aggregation platelet plug blocks blood loss in small vessels not as good in larger vessels

Hemostasis Third -

Coagulation Gel formation

(clotting) in blood traps formed elements

Thrombosis - clotting in a normal vessel

Hemorrhage - slow clotting leading to a bleed

Hemostasis - Coagulation A complicated

process that works in a positive feedback cascade

3 pathways - extrinsic, intrinsic and common

Pathways involve 12 factors in clot formation

Hemostasis - Coagulation

Overview

Stage 1: Prothrombinase formation Prothrombinase

catalyzes Thrombin formation from Prothrombin

Stage 1 has 2 parts Part 1: Extrinsic

Pathway • Rapid (seconds)• Tissue factor

(TF) enters blood from tissue

• Ultimately activates prothrombinase

Hemostasis - Coagulation

Extrinsic PathwayExtrinsic Pathway Intrinsic PathwayIntrinsic Pathway

Prothrombinase

Stage 1: Prothrombinase formation (cont.) Part 2: Intrinsic

Pathway Slower (minutes) Activators in blood -

damaged red blood or endothelial cells activate clotting

Extrinsic pathway also activates Intrinsic pathway

Ultimately activates prothrombinase

Ca2+ required for activation of both paths!

Hemostasis - Coagulation

Extrinsic PathwayExtrinsic Pathway Intrinsic PathwayIntrinsic Pathway

Prothrombinase

Hemostasis - Coagulation Stage 2 - Common

Pathway Thrombin Formation

requires enzyme Prothrombinase w/ Ca++

catalyzes prothrombin conversion to thrombin

Thrombin accelerates formation of prothrombinase (positive feedback)

Thrombin accelerates platelet activation (positive feedback)

Prothrombinase

CommonPathway

+

2.

+

Hemostasis - Coagulation

Stage 3 - Common Pathway Fibrin formation

activated enzyme thrombin w/ Ca++

catalyzes fibrinogen fibrin

• fibrinogen (soluble)• fibrin (insoluble)

Fibrin Protein threads attach to

vessel surface Absorbs/inactivates 90%

of thrombin, limits clot formation

3.

Overview

Hemostasis - Coagulation

Hemostasis - Coagulation

Clot retraction and repair Clot retraction also known as syneresis Platelets continue to pull on fibrin threads

closing wound Formed elements trapped in fibrin threads,

some serum may leak out Hemostatic control mechanisms

Important that clot formation remains local, not systemic

Several mechanisms work together: fibrin absorbing thrombin removal of local clotting factors - washed away endothelial cells inhibit platelet aggregation

Hemostasis - Coagulation Fibrinolysis - dissolution of a

clot, begins within 2 days Plasminogen trapped in clot Many factors convert

plasminogen into plasmin (fibrinolysin)

thrombin activated factor XII tissue plasminogen activator

(t-PA) Plasmin

Digests fibrin threads Inactivates fibrinogen,

prothrombin, and several clotting factors

Hemostasis - Coagulation Thrombolytic (clot-dissolving) agents that can

be used clinically Chemical substances that activate plasminogen Streptokinase, tissue plasminogen activator (t-

PA)

Anticoagulants present in blood - heparin Produced by mast cells, basophils Used clinically to prevent blood clotting in blood

samples Inhibits thrombin and intrinsic pathway

Hemostasis - Coagulation Other anticoagulants

Warfarin (coumadin) - Vitamin K antagonist slow acting, takes days to start and stop rat poison Vitamin K

• produced by gut bacteria• required for synthesis of factors II (prothrombin), VII, IX,

X

Aspirin blocks platelet aggregation prevents formation of thromboxane A2

CPD (citrate phosphate dextrose) removes Ca2+

Used in blood banks

Hemostasis - Coagulation Intravascular Clotting

Roughened endothelium (atherosclerosis, trauma, infection) or slow blood flow may result in spontaneous clot (thrombus) formation, thrombosis

Thrombus released into blood becomes embolus

pulmonary embolus also may be air or debris

Angioplasty - may trigger thrombus

Blood Types

Agglutinins Naturally occurring antibodies produced in response to the

agglutinogens not present in your blood React in antigen-antibody response to blood not of your type

AB - universal recipients O - universal donors

• ABO blood typing– 2 glycolipid agglutinogens, A + B– one gene from each parent, A, B or O– 6 combinations - AA, AB, AO, BB, BO, OO (no agglutinogens)

• RBC surface has genetically determined antigens, agglutinogens

Blood Types

Blood Types Rh typing - Rhesus monkey

With Rh antigens are Rh+

Without Rh agglutinogens Rh-

normally blood does not contain Rh agglutinins

body only makes agglutinins in response to exposure

Rh sensitivity does not occur until second transfusion

hemolytic disease of the newborn

Blood Types Hemolytic

disease of the newborn