University of Jordan1 Body Fluids & Blood. University of Jordan2.

University of Jordan 1

Body Fluids & Blood





Movement of water between compartments

Normally, cells neither shrink or swell because intracellular and interstitial fluids have the same osmolarity

Increasing osmolarity of interstitial fluid draws water out of cells and cells shrink

Decreasing osmolarity of interstitial fluid causes cells to swell

Changes in osmolarity most often result from changes in Na+ concentration

Water intoxication – drinking water faster than the kidneys can excrete it

Can lead to convulsions, coma or death


Electrolytes in body fluids Ions form when electrolytes dissolve ad dissociate 4 general functions

Control osmosis of water between body fluid compartments

Help maintain the acid-base balance Carry electrical current Serve as cofactors


Concentrations in body fluids

Concentration of ions typically expressed in milliequivalents per liter (mEq/liter)

Na+ or Cl- number of mEq/liter = mmol/literCa2+ or HPO4

2- number of mEq/liter = 2 x mmol/liter

Chief difference between 2 ECF compartments (plasma and interstitial fluid) is plasma contains many more protein anions

Largely responsible for blood colloid osmotic pressure


ICF differs considerably from ECF

ECF most abundant cation is Na+, anion is Cl- ICF most abundant cation is K+, anion are

proteins and phosphates (HPO42-)

Na+ /K+ pumps play major role in keeping K+

high inside cells and Na+ high outside cell


Sodium Na+

Most abundant ion in ECF 90% of extracellular cations Plays pivotal role in fluid and electrolyte balance because it

account for almost half of the osmolarity of ECF Level in blood controlled by

Aldosternone – increases renal reabsorption ADH – if sodium too low, ADH release stops Atrial natriuretic peptide – increases renal excretion


Chloride Cl-

Most prevalent anions in ECF Moves relatively easily between ECF and ICF because most

plasma membranes contain Cl- leakage channels and antiporters

Can help balance levels of anions in different fluids Chloride shift in RBCs

Regulated by ADH – governs extent of water loss in urine Processes that increase or decrease renal reabsorption of Na+

also affect reabsorption of Cl-


Potassium K+

Most abundant cations in ICF Key role in establishing resting membrane

potential in neurons and muscle fibers Also helps maintain normal ICF fluid volume Helps regulate pH of body fluids when

exchanged for H+

Controlled by aldosterone – stimulates principal cells in renal collecting ducts to secrete excess K+


Bicarbonate HCO3-

Second most prevalent extracellular anion Concentration increases in blood passing through systemic

capillaries picking up carbon dioxide Carbon dioxide combines with water to form carbonic

acid which dissociates Drops in pulmonary capillaries when carbon dioxide

exhaled Chloride shift helps maintain correct balance of anions in

ECF and ICF Kidneys are main regulators of blood HCO3

-

Can form and release HCO3- when low or excrete excess


Blood Liquid connective tissue 3 general functions1. Transportation

Gases, nutrients, hormones, waste products

2. Regulation pH, body temperature, osmotic pressure

3. Protection Clotting, white blood cells, proteins


Components of Blood Blood plasma – water liquid extracellular

matrix 91.5% water, 8.5% solutes (primarily proteins) Hepatocytes synthesize most plasma proteins

Albumins, fibrinogen, antibodies Other solutes include electrolytes, nutrients,

enzymes, hormones, gases and waste products Formed elements – cells and cell fragments

Red blood cells (RBCs) White blood cells (WBCs) Platelets



Composition of Blood Plasma:

Straw-colored liquid. Consists of H20 and dissolved solutes.

Ions, metabolites, hormones, antibodies. Na+ is the major solute of the plasma.

Plasma proteins: Constitute 7-9% of plasma.

Albumin: Accounts for 60-80% of plasma proteins. Provides the colloid osmotic pressure needed to draw

H20 from interstitial fluid to capillaries. Maintains blood pressure.


Plasma proteins (continued): Globulins:

a globulin: Transport lipids and fat soluble vitamins.

b globulin: Transport lipids and fat soluble vitamins.

g globulin: Antibodies that function in immunity.

Fibrinogen: Constitutes 4% of plasma proteins. Important clotting factor.

Converted into fibrin during the clotting process.

Composition of the Blood (continued)


Serum: Fluid from clotted blood.

Does not contain fibrinogen.

Plasma volume: Number of regulatory mechanisms in the body maintain

homeostasis of plasma volume. Osmoreceptors. ADH. Renin-angiotensin-aldosterone system.

Composition of the Blood (continued)


Formed Elements of Blood


Formation of Blood Cells Negative feedback systems regulate the total number of RBCs

and platelets in circulation Abundance of WBC types based of response to invading

pathogens or foreign antigens Hemopoiesis or hemotopoiesis Red bone marrow primary site Pluripotent stem cells have the ability to develop into many

different types of cells



Formation of Blood Cells Pluripotent stem cells produce

Myeloid stem cells Give rise to red blood cells, platelets, monocytes, neutrophils,

eosinophils and basophils Lymphoid stem cells give rise to

Lymphocytes Hemopoietic growth factors regulate differentiation and proliferation

Erythropoietin – RBCs Thrombopoietin – platelets Colony-stimulating factors (CSFs) and interleukins – WBCs


Leukopoiesis Cytokines stimulate different types and stages of WBC

production. Multipotent growth factor-1, interleukin-1, and interleukin-

3: Stimulate development of different types of WBC cells.

Granulocyte-colony stimulating factor (G-CSF): Stimulates development of neutrophils.

Granulocyte-monocyte colony stimulating factor (GM-CSF): Simulates development of monocytes and eosinophils.


Erythrocytes Flattened biconcave discs. Provide increased surface area through which gas can

diffuse. Lack nuclei and mitochondria.

Half-life ~ 120 days. Each RBC contains 280 million hemoglobin with 4

heme chains (contain iron). Removed from circulation by phagocytic cells in

liver, spleen, and bone marrow.


Leukocytes Contain nuclei and mitochondria. Move in amoeboid fashion.

Can squeeze through capillary walls (diapedesis). Almost invisible, so named after their staining properties.

Granular leukocytes: Help detoxify foreign substances.

Release heparin. Agranular leukocytes:

Phagocytic. Produce antibodies.


Platelets (thrombocytes)

Smallest of formed elements. Are fragments of megakaryocytes. Lack nuclei.

Capable of amoeboid movement. Important in blood clotting:

Constitute most of the mass of the clot. Release serotonin to vasoconstrict and reduce blood flow

to area. Secrete growth factors:

Maintain the integrity of blood vessel wall. Survive 5-9 days.


Blood Cells and Platelets


Hematopoiesis

Undifferentiated cells gradually differentiate to become stem cells, that form blood cells.

Occurs in myeloid tissue (bone marrow of long bones) and lymphoid tissue.

2 types of hematopoiesis: Erythropoiesis:

Formation of RBCs. Leukopoiesis:

Formation of WBCs.


Erythropoiesis

Active process. 2.5 million RBCs are produced every second.

Primary regulator is erythropoietin. Binds to membrane receptors of cells that will become erythroblasts. Erythroblasts transform into normoblasts. Normoblasts lose their nuclei to become reticulocytes. Reticulocytes change into mature RBCs.

Stimulates cell division. Old RBCs are destroyed in spleen and liver.

Iron recycled back to myeloid tissue to be reused in hemoglobin production. Need iron, vitamin B12 and folic acid for synthesis.


Red Blood Cells/ Erythrocytes Contain oxygen-carrying protein hemoglobin Production = destruction with at least 2 million new RBCs per

second Biconcave disc – increases surface area Strong, flexible plasma membrane Glycolipids in plasma membrane responsible for ABO and Rh

blood groups Lack nucleus and other organelles

No mitochondria – doesn’t use oxygen


Hemoglobin

Globin – 4 polypeptide chains Heme in each of 4 chains Iron ion can combine reversibly with one oxygen molecule Also transports 23% of total carbon dioxide

Combines with amino acids of globin Nitric oxide (NO) binds to hemoglobin

Releases NO causing vasodilation to improve blood flow and oxygen delivery


Shapes of RBC and Hemoglobin


Red Blood Cells RBC life cycle

Live only about 120 days Cannot synthesize new components – no nucleus Ruptured red blood cells removed from circulation and

destroyed by fixed phagocytic macrophages in spleen and liver

Breakdown products recycled Globin’s amino acids reused Iron reused Non-iron heme ends as yellow pigment urobilin in urine

or brown pigment stercobilin in feces


Red blood celldeath andphagocytosis

Key:

in blood

in bile

Macrophage inspleen, liver, orred bone marrow

1

Globin


Key:

in blood

in bile


Heme2

1

Aminoacids

Reused forprotein synthesisGlobin


Key:

in blood

in bile


Heme

3

2

1

Aminoacids



Transferrin

Fe3+

Key:

in blood

in bile


Heme

4

3

2

1

Aminoacids



Transferrin

Fe3+

Liver

Key:

in blood

in bile


FerritinHeme

54

3

2

1

Aminoacids



Transferrin

Fe3+

Fe3+ Transferrin

Liver

Key:

in blood

in bile


FerritinHeme

654

3

2

1

Aminoacids



Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile


FerritinHeme Fe3+

7

654

3

2

1

Aminoacids


Circulation for about120 days


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile

Erythropoiesis inred bone marrow


FerritinHeme Fe3+

8

7

654

3

2

1

Aminoacids




Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile



FerritinHeme

Biliverdin Bilirubin

Fe3+

9

8

7

654

3

2

1

Aminoacids



Bilirubin


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile



FerritinHeme


Fe3+

10

9

8

7

654

3

2

1

Aminoacids


Stercobilin

Bilirubin

Urobilinogen

Feces

Smallintestine


Bacteria

Bilirubin


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile



FerritinHeme


Fe3+

12

1110

9

8

7

654

3

2

1

Aminoacids


Urine

Stercobilin

Bilirubin

Urobilinogen

Feces

Smallintestine


Bacteria

Bilirubin


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile


Kidney


Ferritin

Urobilin

Heme


Fe3+

13 12

1110

9

8

7

654

3

2

1

Aminoacids


Urine

Stercobilin

Bilirubin

Urobilinogen

Feces

Largeintestine

Smallintestine


Bacteria

Bilirubin


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile


Kidney


Ferritin

Urobilin

Heme


Fe3+

14

13 12

1110

9

8

7

654

3

2

1

Formation and Destruction of RBC’s


Erythropoiesis

Starts in red bone marrow with proerythroblast

Cell near the end of development ejects nucleus and becomes a reticulocyte

Develop into mature RBC within 1-2 days

Negative feedback balances production with destruction

Controlled condition is amount of oxygen delivery to tissues

Hypoxia stimulates release of erythropoietin


White Blood Cells/ Leukocytes Have nuclei Do not contain hemoglobin Granular or agranular based on staining highlighting large

conspicuous granules Granular leukocytes

Neutrophils, eosinophils, basophils Agranular leukocytes

Lymphocytes and monocytes


Types of White Blood Cells


Functions of WBCs Usually live a few days Except for lymphocytes – live for months or years Far less numerous than RBCs Leukocytosis is a normal protective response to

invaders, strenuous exercise, anesthesia and surgery

Leukopenia is never beneficial General function to combat invaders by

phagocytosis or immune responses


Emigration of WBCs Many WBCs leave the

bloodstream Emigration (formerly

diapedesis) Roll along endothelium Stick to and then

squeeze between endothelial cells

Precise signals vary for different types of WBCs


WBCs Neutrophils and macrophages are active phagocytes

Attracted by chemotaxis Neutrophils respond most quickly to tissue damage

by bacteria Uses lysozymes, strong oxidants, defensins

Monocytes take longer to arrive but arrive in larger numbers and destroy more microbes Enlarge and differentiate into macrophages


WBCs Basophila leave capillaries and release granules

containing heparin, histamine and serotonin, at sites of inflammation Intensify inflammatory reaction Involved in hypersensitivity reactions (allergies)

Eosinophils leave capillaries and enter tissue fluid Release histaminase, phagocytize antigen-antibody

complexes and effective against certain parasitic worms


Lymphocytes Lymphocytes are the major soldiers of the immune

system B cells – destroying bacteria and inactivating their

toxins T cells – attack viruses, fungi, transplanted cells,

cancer cells and some bacteria Natural Killer (NK) cells – attack a wide variety of

infectious microbes and certain tumor cells


Platelets/ Thrombocytes Myeloid stem cells develop eventually into a

megakaryocyte Splinters into 2000-3000 fragments Each fragment enclosed in a piece of plasma

membrane Disc-shaped with many vesicles but no nucleus Help stop blood loss by forming platelet plug Granules contain blood clot promoting chemicals Short life span – 5-9 days


Stem cell transplants Bone marrow transplant

Recipient's red bone marrow replaced entirely by healthy, noncancerous cells to establish normal blood cell counts

Takes 2-3 weeks to begin producing enough WBCs to fight off infections

Graft-versus-host-disease – transplanted red bone marrow may produce T cells that attack host tissues

Cord-blood transplant Stem cells obtained from umbilical cord shortly before birth Easily collected and can be stored indefinitely Less likely to cause graft-versus-host-disease


Hemostasis Sequence of responses that stops bleeding 3 mechanisms reduce blood loss1. Vascular spasm

Smooth muscle in artery or arteriole walls contracts

2. Platelet plug formation Platelets stick to parts of damaged blood vessel, become

activated and accumulate large numbers

3. Blood clotting (coagulation)


Platelet Plug Formation


Blood Clotting3. Blood clotting

Serum is blood plasma minus clotting proteins

Clotting – series of chemical reactions culminating in formation of fibrin threads

Clotting (coagulation) factors – Ca2+, several inactive enzymes, various molecules associated with platelets or released by damaged tissues


3 Stages of Clotting1. Extrinsic or intrinsic pathways

lead to formation of prothrombinase

2. Prothrombinase converts prothrombin into thrombin

3. Thrombin converts fibrinogen (soluble) into fibrin (insoluble) forming the threads of the clot


Blood Clotting Extrinsic pathway

Fewer steps then intrinsic and occurs rapidly Tissue factor (TF) or thromboplastin leaks into the blood

from cells outside (extrinsic to) blood vessels and initiates formation of prothrombinase

Intrinsic pathway More complex and slower than extrinsic Activators are either in direct contact with blood or

contained within (intrinsic to) the blood Outside tissue damage not needed Also forms prothrombinase


Blood Clotting: Common pathway

Marked by formation of prothrombinase Prothrombinase with Ca2+ catalyzes conversion of

prothrombin to thrombin Thrombin with Ca2+ converts soluble fibrinogen into

insoluble fibrin Thrombin has 2 positive feedback effects

Accelerates formation of prothrombinase Thrombin activates platelets Clot formation remains localized because fibrin absorbs

thrombin and clotting factor concentrations are low


Blood Clotting Function of platelets:

Platelets normally repelled away from endothelial lining by prostacyclin (prostaglandin).

Do not want to clot normal vessels. Damage to the endothelium wall:

Exposes subendothelial tissue to the blood.


Blood Clotting (continued)

Platelet release reaction: Endothelial cells secrete von Willebrand factor to cause

platelets to adhere to collagen. When platelets stick to collagen, they degranulate as

platelet secretory granules: Release ADP, serotonin and thromboxane A2.

Serotonin and thromboxane A2 stimulate vasoconstriction. ADP and thromboxane A2 make other platelets “sticky.”

Platelets adhere to collagen. Stimulates the platelet release reaction.

Produce platelet plug. Strengthened by activation of plasma clotting factors.


Platelet plug strengthened by fibrin. Clot reaction:

Contraction of the platelet mass forms a more compact plug.

Conversion of fibrinogen to fibrin occurs. Conversion of fibrinogen to fibrin:

Intrinsic Pathway: Initiated by exposure of blood to a negatively charged

surface (collagen). This activates factor XII (protease), which activates other

clotting factors. Ca2+ and phospholipids convert prothrombin to thrombin.

Thrombin converts fibrinogen to fibrin. Produces meshwork of insoluble fibrin polymers.




Extrinsic pathway: Thromboplastin is not a part of the blood, so

called extrinsic pathway. Damaged tissue releases thromboplastin.

Thromboplastin initiates a short cut to formation of fibrin.




Dissolution of Clots Activated factor XII converts an inactive molecule into the

active form (kallikrein). Kallikrein converts plasminogen to plasmin.

Plasmin is an enzyme that digests the fibrin. Clot dissolution occurs.

Anticoagulants: Heparin:

Activates antithrombin III. Coumarin:

Inhibits cellular activation of vitamin K.


Blood Groups and Blood Types Agglutinogens – surface of RBCs contain genetically

determined assortment of antigens Blood group – based on presence or absence of

various antigens At least 24 blood groups and more than 100 antigens

ABO and Rh


RBC Antigens and Blood Typing

Each person’s blood type determines which antigens are present on their RBC surface.

Major group of antigens of RBCs is the ABO system:

Type AB:Both A and B antigens present.

Type O:Neither A or B antigens present.

Type A:Only A antigens present.

Type B:Only B antigens present.


RBC Antigens and Blood Typing (continued)

Each person inherits 2 genes that control the production of ABO groups.

Type A:May have inherited A gene from each parent.May have inherited A gene from one parent and O gene from the other.

Type B:May have inherited B gene from each parent.May have inherited B gene from one parent and O gene from the other parent.

Type AB:Inherited the A gene from one parent and the B gene from the other parent.

Type O:Inherited O gene from each parent.


ABO Blood Group Based on A and B antigens Type A blood has only antigen A Type B blood has only antigen B Type AB blood has antigens A and B

Universal recipients – neither anti-A or anti-B antibodies

Type O blood has neither antigen Universal donor

Reason for antibodies presence not clear


Antigens and Antibodies of ABO Blood Types


Rh Factor

Another group of antigens found on RBCs. Rh positive:

Has Rho(D) antigens. Rh negative:

Does not have Rho(D) antigens. Significant when Rh- mother gives birth to Rh+ baby.

At birth, mother may become exposed to Rh+ blood of fetus. Mother at subsequent pregnancies may produce antibodies

against the Rh factor. Erythroblastosis fetalis:

Rh- mother produces antibodies, which cross placenta. Hemolysis of Rh+ RBCs in the fetus.


Rh blood group People whose RBCs

have the Rh antigen are Rh+

People who lack the Rh antigen are Rh-

Normally, blood plasma does not contain anti-RH antibodies

Hemolytic disease of the newborn (HDN) – if blood from Rh+ fetus contacts Rh-mother during birth, anti-Rh antibodies made

Affect is on second Rh+ baby

Hemolytic Disease


Typing Blood Single drops of blood

are mixed with different antisera

Agglutination with an antisera indicates the presence of that antigen on the RBC


Transfusion Reactions

If blood types do not match, the recipient’s antibodies attach to donor’s RBCs and agglutinate.

Type O: Universal donor:

Lack A and B antigens. Recipient’s antibodies

cannot agglutinate the donor’s RBCs.

Type AB: Universal recipient:

Lack the anti-A and anti-B antibodies.

Cannot agglutinate donor’s RBCs.

Insert fig. 13.6


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University of Jordan1 Body Fluids & Blood. University of Jordan2.

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