B.Pharm sem-I

1.  Students should not use this presentation for
study or any type of examination.
 Students should refer books prescribed in the
syllabus.

2. The Cardiovascular System:
The Blood

3. Blood is a specialized bodily fluid (technically a tissue).
In vertebrates it is composed of blood cells suspended in a
liquid called blood plasma.
Plasma, which comprises 55% of blood fluid, is mostly
water (90% by volume), and contains dissolved proteins,
glucose, mineral ions, hormones, carbon dioxide (plasma
being the main medium for excretory product
transportation), platelets and blood cells themselves.
The blood cells present in blood are mainly red blood cells
(also called RBCs or erythrocytes) and white blood cells,
including leukocytes and platelets (also called
thrombocytes)

5. Blood
 Liquid connective tissue
 3 general functions
1. Transportation
 Gases, nutrients, hormones, waste products
2. Regulation
 pH, body temperature, osmotic pressure
3. Protection
 Clotting, white blood cells, proteins

6. 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

8. Formed Elements of Blood

9. 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
 Red bone marrow primary site

10. 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

11. 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

12. Shapes of RBC and Hemoglobin

13. 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 bilirubin and
biliverdin

14. Formation and Destruction of RBC’s

15. Red blood cell
death and
phagocytosis
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
1
Globin
Red blood cell
death and
phagocytosis
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Heme
2
1
Amino
acids
Reused for
protein synthesis
Globin
Red blood cell
death and
phagocytosis
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Heme
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Heme
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Liver
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme
5
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme
6
5
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+
Globin
+
Vitamin B12
+
Erythopoietin
Key:
in blood
in bile
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme Fe3+
7
6
5
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Circulation for about
120 days
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+
Globin
+
Vitamin B12
+
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme Fe3+
8
7
6
5
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Circulation for about
120 days
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+
Globin
+
Vitamin B12
+
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme
Biliverdin Bilirubin
Fe3+
9
8
7
6
5
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Circulation for about
120 days
Bilirubin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+
Globin
+
Vitamin B12
+
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme
Biliverdin Bilirubin
Fe3+
10
9
8
7
6
5
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Stercobilin
Bilirubin
Urobilinogen
Feces
Small
intestine
Circulation for about
120 days
Bacteria
Bilirubin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+
Globin
+
Vitamin B12
+
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Heme
Biliverdin Bilirubin
Fe3+
12
11
10
9
8
7
6
5
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Urine
Stercobilin
Bilirubin
Urobilinogen
Feces
Small
intestine
Circulation for about
120 days
Bacteria
Bilirubin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+
Globin
+
Vitamin B12
+
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Kidney
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Urobilin
Heme
Biliverdin Bilirubin
Fe3+
13 12
11
10
9
8
7
6
5
4
3
2
1
Amino
acids
Reused for
protein synthesis
Globin
Urine
Stercobilin
Bilirubin
Urobilinogen
Feces
Large
intestine
Small
intestine
Circulation for about
120 days
Bacteria
Bilirubin
Red blood cell
death and
phagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+
Globin
+
Vitamin B12
+
Erythopoietin
Key:
in blood
in bile
Erythropoiesis in
red bone marrow
Kidney
Macrophage in
spleen, liver, or
red bone marrow
Ferritin
Urobilin
Heme
Biliverdin Bilirubin
Fe3+
14
13 12
11
10
9
8
7
6
5
4
3
2
1

16. Copyright 2009, John Wiley & Sons, Inc.
Anemia is defined as a below-normal plasma hemoglobin
concentration resulting from a decreased number of circulating red
blood cells or an abnormally low total hemoglobin content per unit
of blood volume

17. Copyright 2009, John Wiley & Sons, Inc.
Haematinics -Thesea re substancesr equired in the formation of blood,
and are used for treatment of anaemias.
Causes of anaemia-
(a) Blood loss (acute or chronic)
(b) Impaired red cell formation due to:
. Deficiency of essential factors, i.e. iron, vitamin B12folic acid.
erythropoietin deficiency.

18. Copyright 2009, John Wiley & Sons, Inc.
A. Iron
Iron is stored in intestinal mucosal cells as ferritin (an iron-protein
complex) until needed by the body.
Iron deficiency results from acute or chronic blood loss.
Supplementation with ferrous sulfate is required to correct the
deficiency.
B. Folic acid
The primary use of folic acid is in treating deficiency states that arise
from inadequate levels of the vitamin.
Folate deficiency may be caused by 1) increased demand (for
example, pregnancy and lactation), 2) poor absorption
caused by pathology of the small intestine, 3) alcoholism,

19. Copyright 2009, John Wiley & Sons, Inc.
C. Cyanocobalamin (vitamin B12)
Deficiencies of vitamin B12 can result from either low dietary levels
or, more commonly, poor absorption of the vitamin due to the failure
of gastric parietal cells to produce intrinsic factor (as in pernicious
anemia) or a loss of activity of the receptor needed for intestinal
uptake of the vitamin.
Erythropoietin normally made by the kidney, that regulates red
blood cell proliferation and differentiation in bone marrow.
Human erythropoietin, produced by recombinant DNA
technology, is effective in the treatment of anemia caused by end-
stage renal disease, anemia associated with
human immunodeficiency virus infection, and anemia in some
cancer patients. Darbepoetin

20. 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

21. 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

22. Types of White Blood Cells

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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)

31. Platelet Plug Formation

32. 1
Red blood cell
Platelet
Collagen fibers
and damaged
endothelium
Platelet adhesion
1
1
2
Red blood cell
Platelet
Collagen fibers
and damaged
endothelium
Liberated ADP,
serotonin, and
thromboxane A2
Platelet adhesion
1
Platelet release reaction
2
1
2
3
Red blood cell
Platelet
Collagen fibers
and damaged
endothelium
Liberated ADP,
serotonin, and
thromboxane A2
Platelet plug
Platelet adhesion
1
Platelet release reaction
2
Platelet aggregation
3

33. 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

34. 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

35. Tissue trauma
Tissue
factor
(TF)
Blood trauma
Damaged
endothelial cells
expose collagen
fibers
(a) Extrinsic pathway (b) Intrinsic pathway
Activated XII
Ca2+
Damaged
platelets
Ca2+
Platelet
phospholipids
Activated X
Activated
platelets
Activated X
PROTHROMBINASE
Ca2+
V
Ca2+
V
1
Tissue trauma
Tissue
factor
(TF)
Blood trauma
Damaged
endothelial cells
expose collagen
fibers
(a) Extrinsic pathway (b) Intrinsic pathway
Activated XII
Ca2+
Damaged
platelets
Ca2+
Platelet
phospholipids
Activated X
Activated
platelets
Activated X
PROTHROMBINASE
Ca2+
V
Ca2+
Prothrombin
(II)
Ca2+
THROMBIN
(c) Common
pathway
V
1
2
+
+
Tissue trauma
Tissue
factor
(TF)
Blood trauma
Damaged
endothelial cells
expose collagen
fibers
(a) Extrinsic pathway (b) Intrinsic pathway
Activated XII
Ca2+
Damaged
platelets
Ca2+
Platelet
phospholipids
Activated X
Activated
platelets
Activated X
PROTHROMBINASE
Ca2+
V
Ca2+
Prothrombin
(II)
Ca2+
THROMBIN
Ca2+
Loose fibrin
threads
STRENGTHENED
FIBRIN THREADS
Activated XIII
Fibrinogen
(I)
XIII
(c) Common
pathway
V
1
2
3
+
+

36. Blood Clotting
 Extrinsic pathway
 Fewer steps than 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

37. 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

38. 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

39. 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

40. Antigens and Antibodies of ABO Blood
Types

41. 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
 Affect is on second Rh+
baby

42. Typing Blood
 Single drops of blood are
mixed with different
antisera
 Agglutination with an
antisera indicates the
presence of that antigen
on the RBC