Transcript Altered Hematologic Function

Altered Hematologic
Function:
Erythrocytes
Physical Characteristics of
Blood
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Heavier, thicker, and 3-4 X more viscous
than water
38o C (100.4oF)
pH : 7.35 – 7.45
4-6 liters in an adult
Varies with electrolyte concentration and
amount of adipose tissue
Blood Volume
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Blood volume is about 8% of body
weight.
1 kg of blood ≈ 1 L of blood
70 kg X 0.08 = 5.6 Kg = 5.6 L
45 % is formed elements
55% plasma
Plasma
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92 % Water
8% Solutes – organic and inorganic
– Plasma proteins – largest proportion of solutes
 Albumins – 58 % of the proteins – maintain
osmotic (oncotic) pressure – hold water in the
blood
 Globulins – 38 % - antibodies synthesized by
plasma cells
 Clotting factors – fibrinogen – 4 % (Serum
without)
Other components of
plasma
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Nutrients
Hormones
Electrolytes
Waste products
Dissolved gases
Formed elements
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Three types:
Erythrocytes – red blood cells- RBC’s
Leukocytes – white blood cells – WBC’s
Thrombocytes – platelets – cell fragments
Hemopoiesis
(Hematopoiesis)
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All blood cells common from a common
stem cell – Hemocytoblast
These are in the bone marrow (red) and
develop into blood cells as needed by the
body
Mitosis is signaled by biochemicals
released from the body →
Stem cell is signaled to differentiate into
the needed type of blood cell
Hematopoiesis / cell breakdown continue
through life.
Erythrocytes (RBC’s)
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Most abundant blood cell type
Transport gases
Shape is important
– Large surface to volume ratio
– Reversible deformability – can change shape
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Development is called erythopoiesis
– Erythropoietin is a hormone produced by the
kidneys in response to low blood oxygen
levels; signals bone marrow to increase RBC
production
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Cytoplasm is mostly hemoglobin (lacks
organelles, no nucleus)
Made up of 4 peptide chains that form
the globin portion and four molecules of
the pigment heme which contains an atom
of iron
– Oxygen binds to iron in heme (also CO)
– 23 % of CO2 is bound to globin portion
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If there is a problem with any part of the
molecule it may not be functional.
RBC breakdown
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Healthy RBC’s live about 120 days; we
break down about 174 million per minute
RBC’s are removed from circulation by the
liver and spleen
Broken down into heme and globin
portions
Globin is broken down into amino acids
Iron is removed from heme and stored or
recycled
Heme is broken down into biliverdin and
then into bilirubin
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Usually eliminated in bile.
If liver insufficiency, bilirubin
accumulates in blood  Jaundice  too
much  kernicterus
To produce more RBC’s, the body needs
sufficient iron and amino acids as well as
the vitamins folate (folic acid) and
vitamin B12
Abnormalities Anemias
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Anemia is the inability of the blood to
carry sufficient oxygen to the body.
low #’s of RBCs
lack of hemoglobin
Clinical Manifestations
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Pallor
Fatigue
Weakness; exercise intolerance
Dyspnea
Syncope (fainting) and dizziness
Angina
Tachycardia (increased heart rate)
Organ dysfunctions
Classification of Anemias
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Identified by their causes or by the
changes that affect the size, shape or
substance of the erythrocyte
Terms that end with –cytic refer to cell
size, and those that end in –chromic
refer to hemoglobin content.
Macrocytic /
Megaloblastic Anemia
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Characterized by abnormally large stem
cells (megaloblasts) in the marrow that
mature into erythrocytes that are
unusually large in size, thickness and
volume. The hemoglobin content is
normal, so these are normochromic
anemias.
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These anemias are the result of:
– Ineffective DNA synthesis
 Commonly due to folate and B12
(cobalamin) deficiencies – mal-absorption
or malnutrition
 These cells die prematurely, decreasing the
numbers of RBC’s in circulation
Pernicious Anemia
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Common megaloblastic anemia
Caused by a Vitamin B12 deficiency
Pernicious means highly injurious or
destructive – this condition was once fatal
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Can be congenital – baby born with a
deficiency in a protein , intrinsic factor,
necessary to absorb B12 from the
stomach
Adult onset – one example is an
autoimmune dysfunction - type A chronic
atrophic gastritis – where there is
destruction of the gastric mucosa
Most commonly affects people over 30
Females are more prone to pernicious
anemia , and black females have an
earlier onset.
Pernicious Anemia is also associated with:
Heavy alcohol consumption
Hot tea
Cigarette smoking
Other autoimmune conditions
Complete or partial removal of the stomach
can cause intrinsic factor deficiency
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Develops slowly – over 20 - 30 years
Usually severe by the time individual seeks
treatment
Early symptoms ignored because they are
nonspecific and vague- infections, mood
swings, and gastrointestinal, cardiac or
kidney ailments.
Usually a degree of neuropathy occurs
Untreated, it is fatal, due to heart
failure
Folate deficiency anemia
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Folic acid also needed for DNA synthesis
Demands are increased in pregnant and
lactating females
Absorbed from small intestine and does
not require any other elements for
absorption.
Folate deficiency is more common than B12
deficiency
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Folate deficiency is more common than B12
deficiency , esp. in alcoholics and those
who are malnourished because of fat diets
or diets low in vegetables.
Estimated that 10 % of North Americans
are folate deficient.
Specific manifestations include cheilosis,
(scales and fissures of the mouth),
inflammation of the mouth, and ulceration
of the buccal mucosa and tongue.
Microcytic – Hypochromic Anemias
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Characterized by abnormally small RBC’s
that contain reduced amounts of
hemoglobin.
Possible causes:
– Disorders of iron metabolism
– Disorders of porphyrin and heme synthesis
– Disorders of globin synthesis
Iron Deficiency Anemia
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Most common type of anemia throughout the
world.
High risk:
– Individuals living in poverty
– Females of childbearing age
– Children
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Common causes
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Insufficient iron intake
Chronic blood loss – even 2- 4 ml/ day
In men –gastrointestinal bleeding
In women – profuse menstruation, pregnancy
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Other causes:
– Use of medications that cause GI bleeding
– Surgical procedures that decrease stomach
acidity, intestinal transit time, and absorption
– Eating disorders such as pica
Clinical manifestations:
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Early symptoms are nonspecific
Later - changes in epithelial tissue:
– Fingernails become brittle and concave
(koilonychia)
– Tongue papillae atrophy and cause soreness,
redness and burning
– Corners of mouth become dry and sore
– Difficulty in swallowing due to web of mucus
and inflammatory cells at opening of
esophagus
Treatment
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Stop blood loss
Iron replacement therapy
Normocytic –
Normochromic Anemias
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RBC’s are normal in size and
hemoglobin content, but are too few
in number.
Less common than the macrocytic and
microcytic anemias
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Several types that do not have anything
else in common:
– Aplastic
– Posthemorrhagic
– Hemolytic
– Sickle cell
– Anemia of chronic inflammation
Aplastic anemia
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Fortunately, this condition is rare; it means the
RBC’s are not being produced. Bone marrow stem
cells are not functioning.
Can result from disorders of the bone marrow,
such as cancer; autoimmune diseases; renal failure
due to lack of erythropoietin; B12 or folate
deficiency; congenital problems; or it may be
induced by radiation, toxins or the use of some
drugs, such as chloramphenicol.
Treatment – treat the underlying disorder, blood
transfusions, and possibly bone marrow transplant
Posthemorrhagic
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Caused by sudden loss of blood.
Can be fatal if loss exceeds 40- 50 %
of plasma volume.
Treatment is to restore blood volume
by intravenous administration of
saline, dextran, albumin, plasma or
whole blood.
Hemolytic Anemia
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Red blood cells are formed, but are
broken down.
May be acquired or hereditary.
Acquired hemolytic anemia is extrinsic,
due to factors outside the red blood cell,
such as an abnormal autoimmune
response that targets red cells, or by
improper matches during transfusions; or
due to infection, systemic diseases, or
drugs or toxins.
Hereditary or intrinsic hemolytic
anemias:
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Sickle cell anemia – due to a change in
one amino acid in each of the beta-chains in
the globin, under conditions of low oxygen
the hemoglobin forms insoluble threads that
change the shape of the erythrocyte into a
crescent. This shape is not as flexible and
tend to be trapped in the capillaries, where
they obstruct blood flow and cause ischemic
injury.
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The life span of a sickled cell is only 20
days rather than 120, and is removed
from circulation by the spleen.
Either mechanism causes a chronic
anemia.
Sickle crisis: episodes of acute sickling
that block blood flow, posing the threat
of widespread and possibly lifethreatening ischemic organ damage.
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This is an inheritable condition.
If a person has only one defective gene, it is
called sickle cell trait, and the person is
essentially normal. This condition tends to
persist because it protects against malaria.
When a cell becomes infected by the parasite,
the cell sickles and is removed from
circulation, preventing reproduction of the
parasite.
Only when a person inherits two defective
genes does sickle cell anemia occur.
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Thalassemia is another hemolytic disorder
where the alpha or beta chains of the globin
are defective, or the beta chain is not
produced. When the beta protein is lacking,
the alpha protein accumulates and causes
destructive membrane effects, causing these
cells to be rapidly removed from the circulation.
Highest incidence in populations around the
Mediterranean and Southeast Asia.
Problem occurs when two defective genes are
inherited; heterozygotes are essentially normal.
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Thalassemia major is an inherited form of
hemolytic anemia, characterized by red
blood cell (hemoglobin) production
abnormalities. This is the most severe
form of anemia, and the oxygen depletion
in the body becomes apparent within the
first 6 months of life. If left untreated,
death usually results within a few years.
Note the small, pale (hypochromic),
abnormally-shaped red blood cells
associated with thalassemia major.
Myeloproliferative Disorders
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The opposite of anemias – here we have too
many RBC’s.
Polycythemia – excessive production of RBC’s
– Primary polycythemia – cause is unknown,
but is in effect, a benign tumor of the
marrow, leading to increased numbers of
stem cells and therefore RBC’s, and
splenomegally.
– Polycythemia vera – rare, mostly
Northern European Jewish males between
60 – 80 yrs.
Secondary Polycythemia
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Due to the overproduction of
erythropoietin caused by hypoxia. This is
more common.
Seen in:
– Persons living at high altitudes
– Smokers
– COPD patients
– Congestive heart failure patients
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Polcythemia leads to :
– Increased blood volume and viscosity
– Congestion of liver and spleen
– Clotting
– Thrombus formation
– (last two may be due increased numbers of
platelets along with the increase in RBC’s due
to bone marrow dysfunction.)
Clinical manifestation of
Polycythemia
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Headache
Dizziness
Weakness
Increased blood pressure
Itching / sweating
Treatment of polycythemia
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Reduce blood volume by phlebotomy –
300-500 ml.
Treat underlying condition - Stop smoking
Radioactive phosphorus injections
Prevent thrombosis