Blood

Blood The only fluid tissue in the human body Classified as a connective tissue Components of blood

1) Living cells called ________________ Erythrocytes red blood cells

transports oxygen and carbon dioxide Leukocytes white blood cells

defend body against pathogens Platelets cell fragments formed

from megakaryocytes, important in blood clotting

2) Non-living matrix: plasma is the fluid and solutes

Bukar Alibeformed elements

Blood Hematocrit and Beyond When blood is centrifuged

Erythrocytes sink to the bottom (45% of blood, a percentage known as the hematocrit)

Buffy coat contains leukocytes and platelets (less than 1% of blood), the buffy coat is a thin, whitish layer between the erythrocytes and plasma

__________rises to the top (55% of blood)

Average blood volume Women = 5.0 L Men = 5.5 L

Bukar AlibePlasma

kwashiorkor

280-300 milliosmoles per liter (we will use 300 mOsm/L)

Physical Characteristics of Blood Blood is used as a vehicle of transport Color range

Oxygen-rich blood is scarlet red Oxygen-poor blood is dull red

pH between 7.357.45 (________) Blood temperature is slightly higher than body temperature at 38

(100.4F), it transfers heat throughout the body

Blood Plasma is ~90% Water 6-8% proteins which: increase osmotic pressure, buffer H+, increase

blood viscosity, provide fuel during starvation 3 Major Classes of Plasma Proteins (synthesized in liver, except some

globulins synthesized by lymphocytes) Albumins: Major contributor to plasma oncotic osmotic pressure

and act as carriers Globulins: Carriers, Clotting factors, Precursor proteins

(angiotensinogen), Immunoglobulins Fibrinogen: Blood Clotting

Nutrients: glucose, amino acids, lipids, vitamins Wastes: urea, bilirubin, creatinine Gases (dissolved): oxygen, carbon dioxide Hormones Electrolytes (aka _____________)

Relatively high concentrations of Na+ and Cl- Relatively low concentrations of H+, HCO3-, K+, and Ca2+

Ringers Solution A solution of distilled water containing electrolytes and compounds

so that the same concentrations as their occurrence in body fluids. This solution is iso-osmotic to our blood and tissues Why? 280-300 milliosmoles per liter (we will use __________ mOsm/L) Blood and tissue osmolarity must be equal to prevent net movement of fluids

tissue tissue blood blood

Osmosis Water (solvent) diffuses down its concentration gradient

The Link Between Water and Salt Solutes in the body include

electrolytes like sodium, potassium, and calcium ions

Changes in electrolyte balance causes water to move from one compartment to another which alters blood volume and blood pressure and can impair the activity of cells

Water moves from low [solute] to high [solute]=high [solvent] to low [solvent]

Pure water has ______ solute present Water reabsorption follows solute

reabsorption

More solvent

Less solvent

Blood Plasma

Acidosis: blood becomes too acidic (less than 7.35) Alkalosis: blood becomes too basic (greater than 7.45) In each scenario, the respiratory system and kidneys help

restore blood _________ to normal Carbon dioxide can dissolve in water (blood plasma) and

form carbonic acid

CO2 + H2O H2CO3 (carbonic acid) H+ + HCO3- (bicarbonate)

Im an acid!

Acid-Base Balance Normal pH of arterial blood = 7.4

pH < 7.35 = ___________ pH > 7.45 = alkalosis

Most ions originate as by-products of cellular metabolism Complications with acid-base

disturbance Conformation change in protein

structure Changes in excitability of

neurons Changes in balance of other ions Cardiac arrhythmias Vasodilation/vasoconstriction

Acids and Bases

Acids are proton (H+) donors Strong acids dissociate completely and liberate all

of their H+ in water Weak acids, such as carbonic acid, dissociate only

partially Bases are proton (H+) acceptors

Strong bases dissociate easily in water and tie up H+ Weak bases, such as bicarbonate ion and ammonia,

are slower to accept H+

Cellular or Formed Elements

Erythrocytes: Red blood cells (RBCs)

Leukocytes: _________ blood cells (WBCs)

Platelets (cell fragments)

Multipotent stem cell

Bukar Alibewhite

Developmental Aspects of Blood Cells

Sites of blood cell formation The fetal liver and spleen are early sites of

blood cell formation Bone marrow takes over hematopoiesis by

the seventh month Fetal hemoglobin differs from hemoglobin

produced after birth, fetal hemoglobin has a gamma subunit in place of the beta subunit and ______________ affinity for oxygen

Physiologic jaundice results when the liver cannot rid the body of hemoglobin

breakdown products fast enough

Bukar AlibeHIGHER

Erythrocytes

Erythrocytes (red blood cells or RBCs) Main function is to carry oxygen Anatomy of circulating erythrocytes

biconcave disk: large surface area which favors diffusion

Essentially bags of hemoglobin Anucleate (no nucleus) Contain very few organelles No _________________ Use anaerobic glycolysis

5-6 billion RBCs per ml of blood Flexible membrane Also function to maintain osmolarity and

blood/plasma pH

Bukar Alibemitochondria

Hemoglobin in RBCs Hb binds strongly (but reversibly) to oxygen 98.5% oxygen bound to Hb and 1.5% dissolved

in plasma Each hemoglobin molecule has four oxygen

binding sites Globin + 4 heme groups = 4 polypeptides and

_______________ = iron-containing group Iron-containing protein Can also bind to CO2 and H+

Bukar AlibeHEME

Formation of Erythrocytes

Mature RBCs are unable to divide, grow, or synthesize proteins Wear out in 100 to 120 days When worn out, RBCs are eliminated by phagocytes in the spleen or

liver Lost cells are replaced by division of hemocytoblasts in the red bone

marrow __________________ is a component of hemoglobin Normal hemoglobin content of blood

Men: 13 18 gram /dL Women: 12 16 gram /dL

Control of Erythrocyte Production Rate is controlled by a hormone (________________) Kidneys produce most erythropoietin as a response to reduced oxygen levels in the blood (sensed by chemoreceptors) Homeostasis is maintained by negative feedback from blood oxygen levels

Control of Erythrocyte Production

Reduced O2 levels in blood-sensed by chemoreceptors

Stimulus: Decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2 Increased

O2- carrying ability of blood

Kidney releases erythropoietin Enhanced

erythropoiesis Red bone marrow

More RBCs

Normal blood oxygen levels 100 mmHg

Erythropoietin stimulates

60 mmHg

Anemia: Decrease in the oxygen-carrying capacity of blood

Dietary anemia Iron: iron-deficiency anemia Pernicious: lack of Vitamin B12

Hemorrhagic anemia: bleeding Hemolytic anemia

Malaria or Sickle cell anemia Aplastic anemia: bone marrow

defect ________ anemia: kidney disease

Anemia

Leukocytes (white blood cells) Leukocytes (white blood cells or

WBCs) Crucial in the bodys defense

against disease These are complete cells, with a

nucleus and organelles Able to move into and out of blood

vessels (diapedesis) Can move by ____________

motion though tissues Can respond to chemicals released

by damaged tissues (cytokines) 4,000 to 11,000 WBC per cubic

millimeter (microliter) of blood

Bukar Alibeamebolic

Types of Leukocytes Two Major Classes of Leukocytes Granulocytes Granules in their cytoplasm can be stained Possess lobed nuclei Include 1)neutrophils, 2)eosinophils, and 3)basophils

Agranulocytes Lack visible cytoplasmic granules Nuclei are spherical, oval, or kidney-shaped Include:

1)lymphocytes 2)_________________

Abundance of Leukocytes List of the WBCs from most to

least abundant Neutrophils Lymphocytes Monocytes Eosinophils Basophils

Easy way to remember this list Never Let Monkeys Eat Bananas

Granulocyte: Neutrophils Neutrophils are multilobed nucleus with fine granules 40-70% of leukocytes in blood Phagocytes at active sites of infection Secretes ____________________ Circulate in blood 7-10 hours Migrate to tissues for a few days Increase in number during infections

Granulocyte: Eosinophils 1-4% of leukocytes Large brick-red cytoplasmic granules Phagocytes (but ___________ main mechanism of action) Defend against parasitic invaders (e.g. worms) Granules contain toxic molecules that attack parasites

Granulocyte: Basophils

Agranulocytes: Monocytes become Macrophages

4-8% of leukocytes __________________ New monocytes circulate in blood for

a few hours then Migrate to tissues macrophages Wandering macrophages Fixed macrophages

Agranulocytes: Lymphocytes 20-45% of WBCs 3 types of Lymphocytes ____ lymphocytes (B cells) T lymphocytes (T cells) Null cells (also called

natural killer or NK cells)

Lymphocytes: B Cells B cells associated with antibodies 2 major classes of B cells:

1)effector B cells become plasma cells and secrete antibodies

2) __________________ B cell contacts antigen then

become a plasma cell Plasma cell secretes antibodies

(immunoglobulins) Antibodies mark invaders (called

antigens) for destruction Anti=antibody and

Gen=generator

Bukar AlibeMEMORY CELLS

Lymphocytes: T Cells Helper T Cells secrete cytokines that enhance activity of B cells and

other T cells enhances activity of macrophages and NK cells Cytotoxic T Cells kill virus-infected cells, abnormal cells, and bacteria,

Secretory products form pores in target cell membrane, Kills cells by lysis

Memory T cells used for ______________________ infection Suppressor (regulatory) T Cells secrete cytokines that suppress activity

of B cells and other T cells and used to end an immune response

Lymphocytes: Natural Killer Cells (Null Cells)

Recognize abnormal or infected cells cause lysis by secreting ____________

Can attack virus-infected cells without identifying virus Early defense against viral infections Cause lysis

Fast acting early immune response

MHC=major histocompatibility complex

(a) Inhibitory NK cell receptors recognize self MHC class I and restrain NK cell activation.

(b) When unimpeded by the inhibitory receptors, binding of NK cell activation receptors to their ligands on target cells results in NK cell stimulation.

Leukocyte Issues Abnormal numbers of leukocytes

Leukocytosis WBC count above 11,000 leukocytes/mm3 Generally indicates an infection

____________ Abnormally low leukocyte level Commonly caused by certain drugs such as corticosteroids

and anticancer agents Leukemia occurs when bone marrow becomes cancerous, turns out excess WBC

Platelets Platelets (a.k.a. thrombocytes)

Derived from ruptured multinucleate cells ( ___________________)

Needed for the clotting process Normal platelet count = 300,000/mm3(l)

Characteristics of Formed Elements of the Blood

Characteristics of Formed Elements of the Blood

Hematopoiesis Blood cell formation Occurs in red bone marrow All blood cells are derived from

a common stem cell (hemocytoblast)

Hemocytoblast differentiation Lymphoid stem (lymphoblast)

cell produces lymphocytes Myeloid stem (____________)

cell produces all other formed elements

Erythrocyte synthesis stimulated by erythropoietin secreted from kidneys under conditions of low oxygen levels in blood flowing to kidneys

monocyte

Formation of White Blood Cells and Platelets

Controlled by hormones Colony stimulating factors (CSFs) and _____________

prompt bone marrow to generate leukocytes Thrombopoietin stimulates production of platelets

Hemostasis Stoppage of bleeding resulting from a break in a blood vessel Hemostasis involves three phases 1) Vascular _________________ Vasoconstriction causes blood vessel to

spasm Spasms narrow the blood vessel,

decreasing blood loss 2) Platelet plug formation Collagen fibers are exposed by a break

in a blood vessel a platelets become sticky and cling to fibers

Anchored platelets release chemicals to attract more platelets

Platelets pile up to form a platelet plug 3) Coagulation (blood clotting)

Bukar AlibeSPASMS

Platelet Components

Platelet Plug needed for formation of a blood clot Colorless Cell fragments

no _______________ has organelles & granules

100,000 500,000 / mL blood

Dam

aged

tiss

ue

Hea

lthy

tissu

e

Bukar AlibeNUCLEUS

Preventing the Spread of Plug Chemicals that prevent platelet aggregation: Prostacyclin (PGI2) - produced in healthy endothelial cells Nitric oxide released by healthy endothelial cells ______ is an integral membrane protein that keeps ADP levels low 5 factors that activate a platelet plug are highlighted

Bukar AlibeCD39

Aspirin Prevents_____________________activation Inhibits the activation of thromboxane A2

Bukar AlibePLATELET

Hemostasis Coagulation

Injured tissues release tissue factor (TF) PF3 (a phospholipid) interacts with TF, blood protein clotting

factors, and calcium ions to trigger a clotting cascade Prothrombin activator converts prothrombin to thrombin (an

enzyme) Thrombin joins fibrinogen proteins into hair-like molecules of

insoluble fibrin Fibrin forms a meshwork

(the basis for a clot) Blood usually clots within

3 to 6 minutes The clot remains as

endothelium ____________ The clot is broken down

after tissue repair

Bukar AlibeREGENERATES

Intrinsic and Extrinsic Coagulation Pathways

Intrinsic Pathway trigger = exposed collagen

Extrinsic Pathway Requires Tissue Factor III

Role of Thrombin in Blood Clotting

Clot Formation

Fibrinogen

Fibrin (mesh)

(Fibrin clot = blood clot)

Plasminogen

Plasmin

Dissolves Clot

Dissolving a Clot

Requires another cascade initiated by exposure of collagen

plasminogen activators

Undesirable Clotting Thrombus

A clot in an unbroken blood vessel Can be deadly in areas like the

heart or brain __________________

A thrombus that breaks away and floats freely in the bloodstream

Can later clog vessels in critical areas such as the brain

Bukar AlibeEMBOLUS

Role of Coagulation Factors in Clot Formation Disorders

Hemophilia: a group of genetic disorders caused by deficiency of gene for specific coagulation factors

Von Willebrands disease: reduced levels of vWf and decreases platelet plug formation

Vitamin K deficiencies cause decreased synthesis of clotting factors

_______________________ Platelet deficiency Even normal movements can cause

bleeding from small blood vessels that require platelets for clotting

Bukar AlibeTHROMBOCYTOPENIA

Blood Groups and Transfusions

Large __________________ of blood have serious consequences Loss of 1530% causes weakness Loss of over 30% causes shock, which can be fatal

Transfusions are the only way to replace blood quickly Transfused blood must be of the same or compatible blood group(s)

Bukar AlibeLOSSES

Human Blood Groups Blood contains genetically

determined proteins _______________(a substance the

body recognizes as foreign) may be attacked by the immune system

Antibodies are the recognizers that attack foreign cells

Blood is typed by using antibodies that will cause blood with certain proteins to clump (agglutination)

There are over 30 common red blood cell antigens

The most vigorous transfusion reactions are caused by ABO and Rh blood group antigens

Bukar AlibeANTIGENS

ABO Blood Groups

AB+

O-

ABO Blood Groups Blood type AB can receive A, B, AB, and O

blood, so AB+ is the universal recipient Blood type B can receive B

and O blood Blood type A can receive

A and O blood Blood type O can receive O blood, so O- is the universal donor Blood types: A, B, AB, O Due to antigens on surface of RBCs Type ___ A antigens, anti-B antibodies Type B B antigens, anti-A antibodies Type AB A and B antigens, no A or B

antibodies Type O no modified antigens, anti-A and

anti B antibodies

Bukar AlibeA

Blood Typing Blood samples are mixed with anti-A

and anti-B serum ______________ or no agglutination

leads to determining blood type Typing for ABO and Rh factors is

done in the same manner Cross matchingtesting for

agglutination of donor RBCs by the recipients serum, and vice versa

Bukar AlibeAGGLUTINATION

Rh Blood Groups

Named because of the presence or absence of one of eight Rh antigens (agglutinogen D) that was originally defined in Rhesus monkeys Most Americans are Rh+ (Rh positive) Problems can occur in mixing Rh+ blood into a body with

Rh (Rh________________) blood

Bukar AlibeNEGATIVE

Rh Dangers During Pregnancy: Erythroblastosis fetalis, Rhesus disease

The mismatch of an Rh mother carrying an Rh+ baby can cause problems for the unborn child The first pregnancy usually proceeds without problems The immune system is sensitized after the first pregnancy In a second pregnancy, the mothers immune system produces

antibodies to attack the Rh+ blood (hemolytic disease of the newborn)

Danger occurs only when the mother is Rh and the father is Rh+, and the child inherits the Rh+ factor

A R_____________ shot can prevent formation of anti-Rh+ antibodies in mothers blood-it binds to the

Rh antigen on 1st babys fetal blood, so mom never has an immune response

fetal rhogam

Bukar AlibehoGAM