University of Jordan 1

BODY FLUIDS &

BLOOD
Tortora,
Ebaa M Alzayadneh, DDS, PhD
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Body Fluid Compartments

40%

20%
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Source of daily water

normal conditions
 Renal excretion of water is regulated
Route ml/day Water Normal Hot Prolonge
loss temp. weather d
exercise
Water intake
Fluid 1200 Insensible
In food 1000 loss
Metabolic product 300 Skin 350 350 350
Total 2500 Lungs 350 250 650
Sweat 100 1400 5000
Water output Feces 200 200 200
Insensible 700 Urine 1500 1200 500
Sweat 100
Feces 200 Total loss 2500 3400 6700
Urine 1500 Intake 2500 3400 6700
Total 2500
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Regulation of water gain (Intake)

Metabolic water volume : depends on level of aerobic
cellular respiration (ATP demand).

Mainly; water intake (drinking): Thirst center in the

hypothalamus
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Regulation of water and solute loss

Although loss of water by sweat and exhalation is
increased during exercise, elimination of excess water
and solutes is mainly controlled by urine output.

The main factor that determines body fluids volume is the

extent of urinary NaCl loss (Water follows solutes).

Variable NaCl intake- variable urinary NaCl loss to

maintain homeostasis.
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Regulation of water and solute loss

increased NaCl intake leads to increased blood volume by
increased water movement from intracellular to ICF.
The three most important hormones that regulate Na and
Cl excretion are Angiotensin II, Aldosterone and ANP.
Ang II : increases NaCl reabsorption in the kidney, water
follows.
Aldosterone: increases NaCl reabsorption in the kidney,
water follows.
ANP: decreases NaCl and water reabsorption; thus
decreases blood volume.
The main hormone that regulate water loss is antidiuretic
hormone (ADH) which decreases water loss from kidney.
Distribution of some cations and anions
in extracellular and intracellular fluid
Cations/ ECF ICF
Anions 280-295
mOsm/kgH2
O

Na+ 145 mEq/L 12 mEq/L

K+ 4 150
Ca++ 5 0.001
Cl- 105 5
HCO3- 25 12
Inorganic 2 100
phosphate
(Pi)+
pH 7.4 7.1
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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
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Osmosis
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Electrolytes in body fluids

Ions form when electrolytes dissolve and dissociate

Functions of electrolytes
Control osmosis of water between body fluid compartments
Help maintain the acid-base balance
Carry electrical current
Serve as cofactors
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Differences between plasma and

interstitial fluids
Chief difference between the two ECF
compartments (plasma and interstitial fluid) is
that plasma contains many more protein
anions.
Largely responsible for blood colloid
osmotic (oncotic) pressure
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ICF differs considerably from ECF

ECF most abundant cation is Na+, anion is Cl-

ICF most abundant cation is K+, anions are mostly
proteins and phosphates (HPO42-)
Na+ /K+ ATPase pumps play major role in keeping K+
high inside cells and Na+ high outside cell
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Blood
Liquid connective tissue
38C, alkaline pH 7.4, 5 L,
3 general functions
1. Transportation
Gases, nutrients, hormones, waste products
2. Regulation
pH, body temperature, osmotic pressure
3. Protection
Clotting, white blood cells, proteins
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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
Hematocrit : percentage of total blood volume
occupied by RBCs, 40-50%, Males>females ?
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Formed Elements of Blood

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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 hematopoiesis : the process of
formed blood cells development
Red bone marrow is the primary site ( after birth)
Pluripotent stem cells have the ability to develop
into many different types of cells
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Formation of Blood Cells

Stem cells in bone marrow
Reproduce themselves
Proliferate and differentiate
progenitor cells: some myeloid stem cells differentiate to this cell
type. Cannot be distinguished microscopically- CFU (E, Meg, GM)
precursor cells (blasts): other myeloid and lymphoid directly diff.
to this type. Can be differentiated microscopically. Develop finally to
the actual blood cells.
Cells enter blood stream through sinusoids
Formed elements do not divide once they leave red bone
marrow, Except lymphocytes
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Formation of Blood Cells

Pluripotent stem cells are divided:
1. Myeloid stem cells
Give rise to red blood cells, platelets, monocytes, neutrophils,
eosinophils and basophils
2. Lymphoid stem cells give rise to
Lymphocytes
Hemopoietic growth factors regulate differentiation and proliferation
of progentitor cells
Erythropoietin (EPO) by the kidney RBCs precursors
Thrombopoietin (TPO) by liver platelets from
megacaryocytes
Cytokines: Colony-stimulating factors (CSFs) and interleukins
WBCs
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Red Blood Cells/ Erythrocytes

Contain oxygen-carrying protein hemoglobin
Production = destruction with about (2 million new
RBCs per second)
Biconcave disc increases surface area
(diffusion)
Strong, flexible plasma membrane-squeeze
Glycolipids in plasma membrane responsible for
ABO and Rh blood groups
Lack nucleus and other organelles
No mitochondria doesnt use up any oxygen
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Hemoglobin
280 million molecule / RBC
A. Globin : 4 polypeptide chains
B. Heme in each of 4 chains
C. Iron (Fe+2) in each heme ion : combine reversibly with
one oxygen molecule ( total O2 in one hemoglobin=4)
Also transports 23% of total carbon dioxide (the rest
dissolved)
Combines with amino acids of globin
Nitric oxide (NO) binds to hemoglobin
Releases NO causing vasodilation to improve blood
flow and oxygen delivery
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Shapes of RBC and Hemoglobin

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Red Blood Cells

RBC life cycle
Live only about 120 days (wear and tear)
It Cannot synthesize new components; no nucleus; fragile
Ruptured red blood cells removed from circulation and
destroyed by fixed phagocytic macrophages in spleen and
liver
Breakdown products are recycled
Globins amino acids reused
Iron reused
Non-iron heme ends up as a yellow pigment (urobilin) in
urine or brown pigment (stercobilin) in feces
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Formation and Destruction of RBCs

Circulation for about
120 days

3 7

Amino Reused for

protein synthesis Fe3+ Transferrin
Globin acids
4 6
5
Fe3+
2 Heme Ferritin Fe3+
Transferrin +
Bilirubin Globin
9 +
Biliverdin Bilirubin Liver Vitamin B12
1 Red blood cell 11
10 +
death and Erythopoietin
Small
phagocytosis
Kidney intestine
Bilirubin
8 Erythropoiesis in
13 12 red bone marrow
Urobilin
Macrophage in Urobilinogen Bacteria Key:
spleen, liver, or
in blood
red bone marrow Stercobilin
Large 14
intestine in bile
Urine Feces
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Erythropoiesis
Starts in red bone marrow with
proerythroblast that devides

Cell near the end of development

ejects nucleus to become a
reticulocyte, bypass to blood

Develop into mature RBC within 1-2

days

Negative feedback balances

production with destruction

Hypoxia stimulates release of

erythropoietin
Reticulocytes count indicates
rate of erythropoiesis
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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

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Types of White Blood Cells

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Functions of WBCs
Usually live a few days
Except for lymphocytes live for months or years
Far less numerous than RBCs
Leukocytosis (high)is a normal protective response to
invaders, strenuous exercise, anesthesia and surgery
Leukopenia is never beneficial (low), chemotherapy or
radiation
General function to combat invaders by phagocytosis or
immune responses
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Emigration of WBCs
Many WBCs leave the
bloodstream( emigration)
Emigration (formerly diapedesis)
Roll along endothelium
Stick to Integrins and then
squeeze between endothelial cells
Precise signals vary for different
types of WBCs (chemotaxis)
Monocytes and granulocytes
never go back to blood stream, but
lymphocytes go back and forth
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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
White blood cells have major histocompatibility
(MHC) antigens (cell markers), however, RBCs
lack MHC but have ABO blood group antigens.
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WBCs
Basophils 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
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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
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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
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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
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Hemostasis
Sequence of responses that stops bleeding
3 mechanisms reduce blood loss
1. 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)
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Platelet Plug
Formation
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Blood Clotting
3. 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
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3 Stages of Clotting

1. 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
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3 Stages of Clotting
1. 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
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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
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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
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Dissolution of Clots: hemostatic

control
Dissolution of clot is called fibrinolysis
plasminogen to plasmin
mediated by activated factor XII, tPA, and thrombin
Plasmin is an enzyme that digests the fibrin.
Clot dissolution occurs.
prostacyclin opposes thromboxane A2 and inhibit platelet
adhesion and release.
Anticoagulants:
Heparin: by mast cells and basophils
Activates antithrombin III.
Warfarin (Coumarin): slower than heparin
Antagonist of vitamin K and thus .
EDTA : in labs, Ca++ chelator
Aspirin: blocks synthesis of thromboxane A2
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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
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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
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Antigens and Antibodies of ABO Blood

Types
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Hemolytic Disease

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 Solution: Should inject
Anti Rh antibodies after
Affect is on second
each delivery
Rh+ baby
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Rh Factor

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 or HDN:
Rh- mother produces antibodies, which cross placenta.
Hemolysis of Rh+ RBCs in the fetus.
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Typing Blood
Single drops of blood are
mixed with different antisera
Agglutination with an antisera
indicates the presence of that
antigen on the RBC
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RBC Antigens and Blood Typing (continued)

Each person inherits 2 genes that control the

production of ABO groups.

Type A: Type AB:

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

one parent and O gene from the

other parent.
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Transfusion Reactions
If blood types do not match,
the recipients antibodies Insert fig. 13.6
attach to donors RBCs and
agglutinate, hemolyze.
Type O:
Universal donor:
Lack A and B antigens.
Recipients antibodies
cannot agglutinate the
donors RBCs.
Type AB:
Universal recipient:
Lack the anti-A and anti-
B antibodies.
Cannot agglutinate donors
RBCs.
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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.
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Blood Clotting (continued)

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.
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Blood Clotting (continued)

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.