Chapter 18

Cardiovascular System: Blood

Hematology

Cells immersed in body fluids:

Blood

Plasma
Formed elements (cells)

Interstitial fluid

Functions of Blood

Transportation

Regulation

Body pH
body temp
Fluid balance

H2O content of cells

BP

http://encarta.msn.com/media_461557603_761578429_-1_1/Lymphocyte.html

Protection

Blood loss
Immunity
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Physical Characteristics of Blood

Components of Blood

Centrifuge

Components of Blood

Components of
Blood: Plasma

>90% water
~7% proteins: albumin,
fibrinogen, globulins
(immunoglobulins)
~2% other solutes:
electrolytes, nutrients, gases,
hormones, wastes

Common Electrolytes in Plasma

Common Nutrients in Plasma

Components of Blood:
Formed Elements

RBC (erythrocyte)
WBC (leukocyte)

Granular leukocytes

Agranular leukocytes

lymphocyte = T, B
& NK cell, monocyte

Platelet
(thrombocyte)

Blood Smear

neutrophil,
eosinophil, basophil

megakaryocyte

Stages of
Hematopoiesis
--Pluripotent
hematopoietic stem
cell=hemocytoblast
--Myeloid stem cells
-Erythroblast
reticulocyte RBC

-Megakaryoblast
megakaryocyte
proplatelet platelet
-Granulocytes (PMN,
basophil, eosinophil)
-Monocyte
macrophage

--Lymphoid stem cells

-T, B & NK cells

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Thrombopoiesis

11

Hemopoietic Growth Factors

Regulate
differentiation &
proliferation

Erythropoietin (EPO)
Thrombopoietin
(TPO)
Cytokines

colony-stimulating
factor (CSF)
interleukin (IL)

Recombinant DNA
advances

Growth factor
production
12

Red Blood Cells or Erythrocytes

Biconcave disk

Increases surface area:volume ratio

Spectrin flexible protein

Anucleate amitotic

Shape of a RBC
13

Hemoglobin: Structure & Fxn

Globin protein consists of 4 polypeptides (22)

1 heme attached to each polypeptide heme contains iron

binds 1 oxygen

Oxyhemoglobin

Deoxyhemoglobin

Carbaminohemoglobin

Myoglobin

14

HgB: Blood Pressure Regulation?

HgB helps regulate nitric oxide (NO)

When released NO induces vasodilation

NO released from endothelial cells

15

Clinical Application: Abnormal HgB

Sickle-cell anemia

Defective HgB gene (HbS)

RBCs become sickle-shaped
in low oxygen situations
Cause anemia, ischemia &
infarction
http://www.nlm.nih.gov/medlineplus/ency/imagepages/1223.htm

16

Formation and Destruction of RBCs: Recycling of HgB

Circulation for about
120 days

3
Reused for
protein synthesis

Amino
acids

Globin

Fe3+

Fe3+ Transferrin

2 Heme

Fe3+

Ferritin
Transferrin
Bilirubin

9
1 Red blood cell

Biliverdin

Bilirubin

11

10

death and
phagocytosis

Small
intestine

Kidney

13

12

Urobilin

Macrophage in
spleen, liver, or
red bone marrow

Bilirubin

Urobilinogen
Stercobilin

Urine

Liver

Feces

+
Globin
+
Vitamin B12
+
Erythopoietin

8 Erythropoiesis in
red bone marrow

Bacteria

Key:
in blood

Large 14
intestine

in bile

17

Formation
and
Destruction
of RBCs:
Recycling of
HgB

18

Erythropoiesis: Production of RBC

Requires protein, lipids, CHO, iron, vB12, folic acid
Three phases in developmental pathway

Reticulocyte Erythrocyte

Reticulocyte count = Diagnostic test

19

Total Erythrocytes (RBC)

Circulating
erythrocytes

# remains constant
Normal RBC count

male 5.4 million/drop

female 4.8
million/drop

Reticulocytes

http://www.nlm.nih.gov/medlineplus/ency/imagepages/1491.htm

Should be ~1% of
circulating RBCs

20

Hematocrit
% blood occupied by RBC

female normal range - 38 - 46%

male normal range - 40 - 54%

21

Erythropoietin Mechanism
Start
Normal blood oxygen levels

Increases
O2-carrying
ability of blood

Stimulus: Hypoxia due to

decreased RBC count,
decreased availability of O2
to blood, or increased
tissue demands for O2

Reduces O2
levels in blood

Enhanced
erythropoiesis
increases RBC
count

Erythropoietin
stimulates red
bone marrow

Kidney (and liver to a

smaller extent) releases
erythropoietin

22

Erythropoietin Mechanism

23

Erythrocyte Disorders
Polycythemia

Compensatory smokers
Relative dehydration
Erythrocytosis EPO high
Induced polycythemia

- Blood doping
recEPO or injecting previously stored RBCs before an
athletic event

more cells available to deliver oxygen to tissues

ii. Dangerous

increases blood viscosity

forces heart to work harder

banned by Olympic committee

i.

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Anemia: Low O2 -carrying capacity

General signs/Sx

Types of anemia:

Hemorrhagic anemia

Hemolytic anemia

Aplastic anemia

Iron-deficiency anemia

Pernicious anemia

Sickle-cell anemia

Fig 1. Normal bone marrow. 30-70% of

marrow space consists of hematopoeitic
cells w/ remainder being fat.

Fig 2. Patient's bone marrow

biopsy w/ almost no
identifiable hematopoeisis.
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White Blood Cells/ Leukocytes

Complete blood cells

Usually live a few days

Far less numerous than

RBCs

Except for lymphocytes

live for months or
years

Leukocytosis
Leukopenia
28

Leukocyte
Functions:
Inflammation &
fight infection

Emigration
Chemotaxis
Diapedesis

Adhesion
molecules
(Selectins &
integrins)

29

Classification of Leukocytes
Granulocytes

neutrophils, eosinophils, basophils,

dendritic cells

Agranulocytes

monocytes (m) or lymphocytes

http://encarta.msn.com/media_461557603_761578429_-1_1/Lymphocyte.html

30

Neutrophils: Polymorphonuclear leukocytes

Aka: PMN, Segs,
Polys

60-70% of circulating
WBCs
Multi-lobed nuclei
Granules = peroxidases,
hydrolytic enz &
defensins
Band (shift)

http://cal.vet.upenn.edu/histo/mammalblood/felbandneutbas.htm

Functions target
bacteria

Lysozymes
Defensin proteins
Strong oxidants
Phagocytosis

http://www.physioweb.org/blood_cells.html

31

Eosinophils (Granulocyte)
http://greenfield.fortunecity.com/rattler/46/blood.htm

~1-4% circulating WBC

Nucleus w/ 2-3 lobes

Large, uniform-sized
granules stain orangered w/ acidic dyes

Functions

Release histaminase

Phagocytize Ab-Ag
complexes

Attack parasitic worms

http://www.physioweb.org/blood_cells.html

32

Basophils (Granulocyte)
< 1% of circulating WBC

Large, dark purple, variablesized granules

Histamine
Irregular, s-shaped, bilobed
nuclei

Functions

Leave capillaries & enter CT

Release heparin, histamine &
serotonin
Intensify the inflammatory &
allergy rxn

Involved with hypersensitivity rxns

33

Identify these cells:

RBC
Eosinophil

PMN

Basophil
34

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Monocyte (Agranulocyte)
3-8% of circulating WBCs
Physical features

U or kidney shaped nucleus

Migratory

Differentiate into macrophage (m)

http://www.physioweb.org/blood_cells.html

Fixed m
Free (wandering) m

Phagocytes

Antigen presenting cell (APC) via

MHC (major histocompatibility
complex)

36

Lymphocyte (Agranulocyte)
General features

~25% of circulating
WBCs
Dark, oval to round
nucleus

Types of lymphocytes

NK cells (Innate)

Viral infected & tumor

cells

http://greenfield.fortunecity.com/rattler/46/blood.htm

B cells (plasma)

Make antibody to
antigens

T cells

virus, fungi, cancer,

some bacteria,
transplants

http://www.phototakeusa.com/results.asp?txtkeys=Dennis+Kunkel

37

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Clinical Application: Leukemia

Acute leukemia

uncontrolled
production of
immature leukocytes

Chronic leukemia

accumulation of
mature WBC in
bloodstream because
they do not die

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Bone Marrow Transplant

Procedure

donor match (MHC)

destroy sick bone marrow
IV transfer of healthy bone
marrow

Risky business!

Tx used for leukemia,

sickle-cell, breast, ovarian
or testicular cancer,
lymphoma or aplastic
anemia

Regimen-related toxicities
Infection
Graft versus host
40

Another option?
Cord blood transplant

More Tolerant Matching

More Quickly Available
Less Graft-Versus-Host
Disease
Stem cells taken from
umbilical cord & frozen painless

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