Altered Hematologic Function: Erythrocytes

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Altered Hematologic FunctionErythrocytes
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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

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Blood Volume

• 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

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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 (Serum
  without)

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Other components of plasma

• Nutrients
• Hormones
• Electrolytes
• Waste products
• Dissolved gases

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Formed elements

• Three types
• Erythrocytes red blood cells- RBCs
• Leukocytes white blood cells WBCs
• Thrombocytes platelets cell fragments

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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.

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Erythrocytes (RBCs)

• 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

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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
• If there is a problem with any part of the
  molecule it may not be functional.

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RBC breakdown

• Healthy RBCs live about 120 days we break down
  about 174 million per minute
• RBCs 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 RBCs, the body needs sufficient
  iron and amino acids as well as the vitamins
  folate (folic acid) and vitamin B12

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Abnormalities Anemias

• Anemia is the inability of the blood to carry
  sufficient oxygen to the body.
• low s of RBCs
• lack of hemoglobin

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Clinical Manifestations

• Pallor
• Fatigue
• Weakness exercise intolerance
• Dyspnea
• Syncope (fainting) and dizziness
• Angina
• Tachycardia (increased heart rate)
• Organ dysfunctions

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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.

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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.

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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 RBCs in circulation

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Pernicious Anemia

• 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.

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• 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

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Folate deficiency anemia

• 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.

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Microcytic Hypochromic Anemias

• Characterized by abnormally small RBCs that
  contain reduced amounts of hemoglobin.
• Possible causes
• Disorders of iron metabolism
• Disorders of porphyrin and heme synthesis
• Disorders of globin synthesis

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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

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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

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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

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Treatment

• Stop blood loss
• Iron replacement therapy

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Normocytic Normochromic Anemias

• RBCs 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

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Aplastic anemia

• Fortunately, this condition is rare it means the
  RBCs 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

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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.

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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.

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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.

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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 life-threatening 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.

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Myeloproliferative Disorders

• The opposite of anemias here we have too many
  RBCs.
• Polycythemia excessive production of RBCs
• Primary polycythemia cause is unknown, but is
  in effect, a benign tumor of the marrow, leading
  to increased numbers of stem cells and therefore
  RBCs, and splenomegally.
• Polycythemia vera rare, mostly Northern
  European Jewish males between 60 80 yrs.

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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

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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 RBCs due to
  bone marrow dysfunction.)

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Clinical manifestation of Polycythemia

• Headache
• Dizziness
• Weakness
• Increased blood pressure
• Itching / sweating

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Treatment of polycythemia

• Reduce blood volume by phlebotomy 300-500 ml.
• Treat underlying condition - Stop smoking
• Radioactive phosphorus injections
• Prevent thrombosis