CARDIOVASCULAR SYSTEM

Clarence L. Nuval, RMT, MD

CARDIOVASCULAR SYSTEM
Three interrelated components:
• Blood
• Heart
• Blood vessels

Three general functions:

• Transportation
• Regulation
• Protection
BLOOD
• Constitutes 20% of
extracellular fluid
• Two components:
• Blood plasma (55%)
• Formed elements (45%)
• Red blood cells (99%)
• White blood cells and
platelets (1%)
BLOOD PLASMA
• Straw-colored liquid that is about 91.5% water and 8.5% solutes
• Consists of plasma proteins (7%)
• Albumin
• Globulin
• Fibrinogen
• Immunoglobulins (or antibodies)
• Also consists of other solutes (1.5%)
• Plasma that lacks coagulation factors is called serum.
FORMED ELEMENTS
Three principal components:
• Red blood cells
• Transport oxygen to body cells and deliver carbon dioxide to
the lungs for excretion
• White blood cells
• Protect from pathogens and other foreign substances
• Platelets
• Promote blood clotting
• Blood cell fragments
FORMED ELEMENTS
HEMOPOIESIS / HEMATOPOIESIS
• The process by which formed elements of blood develop
• Organs involved:
• Before birth (3rd week of gestation)
• Yolk sac of an embryo
• Yolk sac phase
• During fetal life
• Liver, spleen, thymus, lymph node
• Hepatic phase
• Last three months before birth, after birth and throughout life
• Red bone marrow
• Bone marrow phase
RED BLOOD CELLS
RED BLOOD CELLS / ERYTHROCYTES
• Biconcave discs with a
diameter of 7-8 um
• Lack a nucleus and other
organelles
• Contain oxygen-carrying
protein called hemoglobin
• Highly specialised for oxygen
transport
• Life span: 120 days
• “Histologic ruler”
RED BLOOD CELLS / ERYTHROCYTES
The shape of RBCs is maintained by membrane proteins
• Integral membrane proteins
• Glycophorins
• Band 3 proteins

• Peripheral membrane proteins

• Spectrin
• Actin
• Adducin
• Tropomyosin
• Ankyrin
• Band 4.1 protein, band 4.2 protein, band 4.9 protein
RED BLOOD CELLS / ERYTHROCYTES
• Any defect in the expression of genes encoding these cytoskeleton
proteins can result in abnormally shaped and fragile erythrocytes
• E.g. hereditary spherocytosis
• Caused by a primary defect in spectrin gene expression that
results in spherical erythrocytes
• E.g. hereditary elliptocytosis
• Caused by a deficiency in band 4.1 proteins that results in
elliptical erythrocytes
• In both conditions, RBCs are unable to adapt to changes in the
environment, which results in premature destruction of cells or
hemolysis.
RED BLOOD CELLS / ERYTHROCYTES
HEREDITARY HEREDITARY
SPHEROCYTOSIS ELLIPTOCYTOSIS
HEMOGLOBIN
• Protein specialised for
transport of oxygen and
carbon dioxide
• Consists of heme and globin
• Has an iron ion at the center
of each heme ring, which
combines with oxygen
reversibly
BLOOD SMEAR
ABO BLOOD GROUP SYSTEM
• The classification of human blood based on the inherited properties
of RBCs
• Determined by the presence or absence of antigens on the surface of
the cells, which are glycoproteins and glycolipids
• Four primary blood groups:
• Type A
• Type B
• Type AB
• Type O
ABO BLOOD GROUP SYSTEM
• All humans have enzymes that catalyze the synthesis of the O
antigen.
• Individuals with A, B, and AB blood groups have additional enzymes.
• Type A – has N-acetylgalactosaminetransferase
• Type B – has galactose transferase
• Type AB – express both enzymes
• Type O – lack both enzymes
ABO BLOOD GROUP SYSTEM
• Individuals with type A blood group have A antigens and anti-B
antibodies.
• Individuals with type B blood group have B antigens and anti-A
antibodies.
• Individuals with type AB blood group have A and B antigens but do
not have antibodies directed against these antigens.
• Individuals with type O blood group do not have A and B antigens,
but instead, have anti-A and anti-B antibodies.

Antibodies cannot co-exist with their corresponding antigens.

Otherwise, antibodies would attack these antigens present on the cells,
eventually destroying the cells.
RH BLOOD GROUP SYSTEM
• The classification of human blood based on the presence of Rhesus
(Rh) antigen on the surface of the RBCs

• Rh-positive
• Have Rh antigens on the surface
• May receive Rh-positive or Rh-negative blood
• Rh-negative
• Do not have Rh antigens on the surface
• May receive only Rh-negative blood
• As medical technologists, a few of our tasks include blood typing
and crossmatching in the laboratory.

• Blood typing
• A test used to determine an individual’s blood type
• Done prior to crossmatching
• Crossmatching
• A test done prior to blood transfusion, to determine if the donor’s
blood is compatible with the blood of an intended recipient
BLOOD TYPING
• In blood typing, we use three reagents:
• Anti-A serum
• Anti-B serum
• Anti-D serum

• Interpretation of results:
• Agglutination = POSITIVE
• No agglutination = NEGATIVE
BLOOD TYPING
• Anti-A serum produces agglutination with type A blood group, and type AB
blood group together with Anti-B serum.
• Anti-B serum produces agglutination with type B blood group, and type AB
blood group together with Anti-A serum.
• Anti-D serum produces agglutination with Rh positive blood.

• Filipinos normally have either “A +”, “B+”,

“AB+”, or “O +” blood type.

• To remember the reagents:

• “Blue Angel, Yellow Bird”
• Anti-A serum contains a blue dye
• Anti-B serum contains a yellow dye
CONTROL ANTI-A ANTI-B ANTI-D

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RBC LIFE CYCLE
ERYTHROPOIESIS
• Production of RBCs
• Begins with a precursor cell
called proerythroblast
• All cells (beginning with
proerythroblast) contain
nuclei, until the near end of
the development. Upon
ejection of nucleus, the first
anucleate cell from this line is
now called reticulocyte.
ERYTHROPOIESIS
• The reticulocyte is the first
anucleate cell in the
formation of RBCs, however,
it still contains other
organelles such as the
mitochondria, ribosomes and
ER.
• In 1-2 days after release from
the bone marrow,
reticulocytes develop into
matures erythrocytes.
ERYTHROPOIESIS
• Normally, erythropoiesis and
RBC destruction occur at the
same pace.
• If destruction > formation =
responds by speeding up
erythropoiesis
• Hypoxia is the main stimulus
• Stimulates kidney to
release erythropoietin
• Erythropoietin then
stimulates bone marrow
to produce RBCs
WHITE BLOOD CELLS
WHITE BLOOD CELLS

GRANULOCYTES AGRANULOCYTES
• Neutrophil • Lymphocyte
• Eosinophil • Monocyte
• Basophil
WHITE BLOOD CELLS
• Both granulocytes and agranulocytes contain granules, but
granulocytes possess obvious, specifically stained granules in the
cytoplasm

• Basic dyes stain nuclei, granules of basophils and the RNA of the
cytoplasm.
• Acidic dyes stain the RBCs and granules of eosinophils.
WHITE BLOOD CELLS

Neutrophils
• Polymorphonuclear neutrophils (PMNs)
• Most numerous WBCs; most common granulocytes
• Readily identified by their multilobal nucleus; usually 2-4 lobes
• Leave the circulation and migrate to their site of action in the
connective tissue
WHITE BLOOD CELLS

Eosinophils
• Named for the large, eosinophilic, refractile granules in their
cytoplasm
• Typically bilobed nuclei
• Has granules containing histaminase
• Associated with allergic reactions, parasitic infection and chronic
inflammation
WHITE BLOOD CELLS

Basophils
• Named for the numerous large granules in their cytoplasm that stain
with basic dyes
• Least numerous of the WBC
• Has granules containing histamine, leukotrienes, heparin, and
heparan sulfate
• Responsible for severe vascular disturbances associated with
hypersensitivity reactions and anaphylaxis
WHITE BLOOD CELLS

Lymphocytes
• Main functional cells of the lymphatic or immune system
• Most common agranulocytes
• Three functionally distinct types:
• T lymphocytes – differentiate in the thymus
• B lymphocytes – differentiate in the bone marrow
• Natural killer (NK) cells
WHITE BLOOD CELLS
T cells/lymphocytes
• Involved in cell-mediated immunity
• Characterised by presence of T-cell receptors (TCRs)
• Also express CD (cluster of differentiation) markers, that serve
as the cells’ IDs
TYPES OF T CELLS/LYMPHOCYTES
Helper CD4+ T cells
• Only recognise antigens bound to MHC (major histocompatibility
complex) class II
• Critical for induction of an immune response to a foreign antigen

Cytotoxic CD8+ T cells

• Only recognise antigens bound to MHC (major histocompatibility
complex) class I
• Primary effector cells in cell-mediated immunity
TYPES OF T CELLS/LYMPHOCYTES
Regulatory (suppressor) T cells
• Functionally suppress an immune response to foreign and self-
antigen by influencing the activity of other cells in the immune
system

Delta T cells
• Possess a distinct TCR on their surface
• Also known as intraepithelial lymphocytes
• Exist in the skin and mucosa of internal organs
• First line of defense against invading organisms
WHITE BLOOD CELLS
B cells/lymphocytes
• Involved in antibody production
• Differentiate into plasma cells and synthesize antibodies
• Express IgM, IgD and MHC class II
WHITE BLOOD CELLS
NK cells
• Programmed to kill virus-infected cells and tumor cells
• Also secrete interferon-gamma, an antiviral agent
WHITE BLOOD CELLS

Monocytes
• Precursors of the cells of the mononuclear phagocytic system
• Largest of the WBCs
• Typical kidney-shaped nuclei
• Remain in blood for only about 3 days
• Transform into macrophages in target tissues
• Function as antigen-presenting cells in the immune system
LEUKOCYTE MIGRATION / DIAPEDESIS
• Migration of leukocytes
through blood vessels, to site
of target tissue
• Mediated by adhesion
molecules and chemokines
• Selectins – mediate initial
rolling interactions
• Integrins – mediate firm
adhesion
LEUKOCYTE MIGRATION / DIAPEDESIS
Steps:
• In the lumen
• Margination
• Rolling
• Adhesion/sticking
• Across the endothelium
• Squeezing
• In the tissues
• Chemotaxis – movement
along a chemical gradient
PLATELET
PLATELETS / THROMBOCYTES
• Small, membrane-bounded, anucleate cytoplasmic fragments derived
from megakaryocytes
• Function in continuous surveillance of blood vessels, clot formation
and repair of inured tissues
• Life span: 10 days
• Has granules containing serotonin, ADP and thromboxane A2
HEMOSTASIS
• A sequence of responses that stops bleeding and prevents
hemorrhage

• Three mechanisms reduce blood loss:

• Vascular spasm
• Platelet plug formation
• Blood clotting
VASCULAR SPASM
• When damaged, smooth muscles of blood vessels contract
immediately.
• In effect, it reduces blood loss.
PLATELET PLUG
FORMATION
1. Platelet adhesion – platelets
initially adhere to area of
damage in the endothelium

2. Platelet release reaction –

platelets become activated and
start to release their contents,
which play a role in further
vasoconstriction

3. Platelet aggregation – the

gathering of platelets that later
form a mass called platelet
plug
BLOOD CLOTTING / COAGULATION
• A series of chemical reactions that culminates in the formation of
fibrin threads
• Involves clotting factors (Factors I-XIII; no Factor VI)
• Two pathways:
• Intrinsic pathway
• Extrinsic pathway
• (Common pathway)

• Excessive clotting  THROMBOSIS

COAGULATION FACTORS
COAGULATION CASCADE

INTRINSIC PATHWAY EXTRINSIC PATHWAY

• Tissue damage not needed • Tissue damage needed for
for cascade to commence cascade to commence
through this pathway through this pathway

• Factors XII  XI  IX  VIII • Factor III  common pathway

 common pathway
COAGULATION
CASCADE

COMMON PATHWAY
• Factors X  V  II  I
• THROMBIN
• Activated form of
PROTHROMBIN (Factor II)
• Accelerates formation of
prothrombinase, which
accelerates production of
thrombin
• Activates platelets
CLOT RETRACTION
• Consolidation or tightening of the fibrin clot
• Depends on an adequate number of platelets in the clot and other
clotting factors
FIBRINOLYSIS
• Dissolution of a clot
MEDICAL CORRELATES
ANEMIA
• A condition in which the oxygen-carrying capacity of blood is
reduced
• Characterised by reduced number of RBCs or a decreased amount of
hemoglobin in blood
ANEMIA
Causes:
• Inadequate absorption of iron, excessive loss of iron, increased
iron requirement, or insufficient intake of iron
• Inadequate intake of vitamin B12 or folic acid
• Insufficient hemopoiesis
• Excessive loss of RBCs
• Premature rupture of RBC plasma membrane
• Deficient synthesis of hemoglobin
• Destruction of red bone marrow
SICKLE CELL DISEASE
• A condition where RBCs contain Hb-S (instead of the normal Hb-A1)
• Forms long, stiff, rodlike structures that bend the erythrocyte into a
sickle shape
• Die in about 10-20 days
• Manifest with shortness of breath, fatigue, paleness, delayed growth
and development, and jaundice (in rapid breakdown of RBCs)
• May have painful episodes due to deficient oxygen in body organs
• Any activity that reduces the amount of oxygen in the blood may
produce a sickle cell crisis
• I.e. worsening of anemia, abdominal pain, pain in long bones,
fever, shortness of breath
SICKLE CELL DISEASE
• Sickle cell genes are found primarily among populations that live in
the malaria belt around the world, including parts of Mediterranean
Europe, sub-Saharan Africa and tropical Asia.

• Question: How is having sickle cell disease beneficial in individuals

with malaria?
HEMOPHILIA
• An inherited deficiency of clotting in which bleeding may occur
spontaneously or after only minor trauma
• The oldest known hereditary bleeding disorder
• Referred to as “the royal disease,” after Queen Victoria’s sons were
affected with it
• Characterised by subcutaneous and intramuscular hemorrhaging,
nosebleeds, hematuria (blood in urine), and hemarthroses
(hemorrhages in joints) that produces pain and tissue damage

• Hemophilia A – deficiency / absence of Factor VIII

• Hemophilia B – deficiency / absence of Factor IX
LEUKEMIA
• A group of red bone marrow cancers in which abnormal white blood
cells multiply uncontrollably
• Accumulation of cancerous white blood cells interferes with
production of normal red blood cells, white blood cells and platelets
• Hence, patients with leukemia may manifest with anemia (most
common), infection and excessive clotting
• Also, “B cell symptoms” = fever, night sweats, weight loss
• May be acute or chronic
• May be lymphoblastic (derived from lymphoid stem cells) or
myelogenous (derived from myeloid stem cells)