Transcript Altered Hematologic Function: Erythrocytes Physical Characteristics of Blood • Heavier, thicker, and 3-4 X more viscous than water • 38o C (100.4oF) • pH :

Altered Hematologic Function:
Erythrocytes
Physical Characteristics of Blood
• 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
• 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 %
Other components of plasma
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Nutrients
Hormones
Electrolytes
Waste products
Dissolved gases
Formed elements
• Three types:
Erythrocytes – red blood cells- RBC’s
Leukocytes – white blood cells – WBC’s
Thrombocytes – platelets – cell fragments
Hemopoiesis (Hematopoiesis)
• 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)
• Most abundant blood cell type
• Transport gases
• Shape is important
– Large surface to volume ratio
– Reversible deformability – can change shape
• 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
• Cytoplasm is mostly hemoglobin (lacks
organelles)
• 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
• If there is a problem with any part of the
molecule it may not be functional.
RBC breakdown
• 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
• Usually eliminated in bile.
• 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
• Anemia is the inability of the blood to
carry sufficient oxygen to the body.
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low #’s of RBCs
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lack of hemoglobin
Cinical Manifestations
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Pallor
Fatigue
Pallor
Weakness; exercise intolerance
Dyspnea
Syncope (fainting) and dizziness
Angina
Tachycardia (increased heart rate)
Organ dysfunctions
Classification of Anemias
• 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.
• Additional terms:
– Anisocytosis – various sizes
– Poikilocytosis – various shapes
Macrocytic / Megaloblastic Anemia
• 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.
• These anemias are the result of:
– Ineffective DNA synthesis
• Commonly due to folate and B12
(cobalamin) deficiencies – malabsorption or
malnutrition
• These cells die prematurely, decreasing the
numbers of RBC’s in circulation
– DNA synthesis is blocked or delayed, but RNA
replication and protein synthesis are normal.
Pernicious Anemia
• Common megaloblastic anemia
• Caused by a Vitamin B12 deficiency
• Pernicious means highly injurious or
destructive – this condition was once fatal
• 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 PA , 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
• 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, us. due to heart failure
Folate deficiency anemias
• 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
• Folate deficiency is more common than
B12 deficiency , esp. in alcoholics and
those who are malnourished because of
fad 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
• 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
• Most common type of anemia throughout the
world.
• High risk:
– Individuals living in poverty
– Females of childbearing age
– Children
• Common causes
– Insufficient iron intake
– Chronic blood loss – even 2- 4 ml/ day
– In men –gastrointestinal bleeding
– In women – profuse menstruation, pregnancy
• 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:
• 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
• Stop blood loss
• Iron replacement therapy
Sideroblastic Anemia
• Due to inefficient iron uptake, resulting in
abnormal hemoglobin synthesis
• Characterized by the presence of ringed
sideroblasts in the bone marrow – red
cells containing iron granules that have not
been synthesized into hemoglobin, but
instead are arranged in a circle around the
nucleus.
http://sickle.bwh.harvard.edu/sideroblast.jpg
• Can be acquired or hereditary
• Acquired SA is the most common
– May be idiopathic or associated with other
disorders
– Reversible - secondary to alcoholism, drug
reactions, copper deficiency and hypothermia
• Hereditary SA –rare, almost always in
males – probably X-linked recessive gene.
Clinical manifestations
• Along with cardiovascular and respiratory
manifestations of anemia, may also show
signs of iron overload (hemosiderosis)
– Enlargement of spleen and liver
– Bronze tint to skin
– Heart rhythm disturbances
– Impaired growth and development in young
children
Treatment
• Drug therapy – pyridoxine
• Iron overload requires repeated blood
removal – phlebotomies
• Iron chelating agents in anemic individuals
who require transfusions
Normocytic –Normochromic
Anemias
• RBC’s are normal in size and hemoglobin
content, but are too few in number.
• Less common than the macrocytic and
microcytic anemias
• Several types that do not have anything
else in common:
– Aplastic
– Posthemorrhagic
– Hemolytic
– Sickle cell
– Anemia of chronic inflammation
Aplastic anemia
• 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
• 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
• 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:
• 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.
• 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 life-threatening
ischemic organ damage.
http://www.sunyniagara.cc.ny.us/val/sicklecellhigh.html
• 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.
• 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.
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.
http://www.nlm.nih.gov/medlineplus/ency/imagepages/1498.htm
Myeloproliferative Disorders
• 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
• 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
• 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
• Reduce blood volume by phlebotomy –
300-500 ml.
• Treat underlying condition - Stop smoking
• Radioactive phosphorus injections
• Prevent thrombosis