Nursing English Homework
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Hematologyygjg1.pptxHematopoietic Function
Blood Composition
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Summary of Blood Cells
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Hematopoiesis
Stimulus for RBC
Hypoxemia and blood loss as stimuli
Stimulus for WBC
Infection and inflammation
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RBC Hemoglobin Synthesis
Dietary iron is absorbed in the intestine epithelial cells, enter the circulation, and combine with transferrin
From plasma , iron is stored as Ferritin
Iron in the hemoglobin compartment is recycled
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Erythropoiesis
Red cells are produced in the red bone marrow after birth.
Until 5 years of age, almost all bones produce red cells to meet growth needs; after 5 years, bone marrow activity gradually declines.
After 20 years, red cell production takes place mainly in the membranous bones of the vertebrae, sternum, ribs, and pelvis.
With this reduction in activity, the red bone marrow is replaced with fatty yellow bone marrow.
Red cell Production
Erythroblasts are continuously being formed from the pluripotent stem cells in the bone marrow.
They move through a series of divisions to develop into mature red blood cells.
Normoblast to reticulocyte, the red blood cell accumulates hemoglobin as the nucleus condenses and is lost.
The red cell loses its mitochondria and ribosomes.
Red Blood Cells are derived from precursor cells called erythroblasts
During the transformation from normoblast to reticulocyte, the red blood cells accumulate hemoglobin as the nucleus condenses and is finally lost.
Maturation from reticulocyte to erythrocyte takes approximately 24 to 48 hours
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Function of the Red Blood Cell
Transportation of oxygen to the tissues
Hemoglobin binds some carbon dioxide and carries it from the tissues to the lungs.
The hemoglobin molecule is composed of two pairs of structurally different polypeptide chains.
Each of the four polypeptide chains consists of a globin (protein) portion and a heme unit, which surrounds an atom of iron that binds oxygen.
Each molecule of hemoglobin can carry four molecules of oxygen.
Life Span-4 months (120 days)
Aged Red Blood Cell:
Dec metabolic activity
Decline enzyme activity
Decrease adenosine triphosphate (ATP)
Cell membrane fragility-causing red cell to self –destruct
Amino acid from the globin chain and iron from the heme units are salvaged and reused
Bilirubin is conjugated in the liver with glucuronide
Red Cell Destruction
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Bilirubin
The heme unit is converted to bilirubin.
Bilirubin is insoluble in plasma and attaches to plasma proteins for transport.
Unconjugated
Removed from the blood by the liver and conjugated with glucuronide to render it water soluble
Conjugated
Question
Bilirubin is an important indicator of which of the following:
A. Rate of RBC production
B. Rate of hemoglobin production
C. Rate of RBC breakdown
D. Rate of hemoglobin oxidation
Laboratory Tests
Red blood cell count (RBC)
Measures the total number of red blood cells in 1 mm3 of blood
Percentage of reticulocytes (normally approximately 1%)
Provides an index of the rate of red cell production
Hemoglobin (grams per 100 mL of blood)
Measures the hemoglobin content of the blood
Hematocrit
Measures the volume of red cell mass in 100 mL of plasma volume
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Laboratory Tests
Mean Corpuscular Volume (MCV) (85-100fL)
Volume or size of the red cells (microcytic, normocytic, macrocytic)
Mean Corpuscular Hemoglobin Concentration (MCHC) (31-35 g/dL)
Concentration of hemoglobin (account for color) in each cell. (normochromic or hypochromic)
Mean Cell Hemoglobin (MCH) (27-34 pg/cell)
Mass of the red cell (less useful)
Hemostasis
Hemostasis: derives from the Greek meaning “The stoppage of blood flow”
Regulated by activators and inhibitors that maintain blood fluidity
Disorders of hemostasis:
1. Inappropriate formation of clots within the vascular system (thrombus).
2. Failure of blood to clot in response to an appropriate stimulus (bleeding).
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Hemostasis
Three Stages
Vascular Constriction
Formation of the Platelet Plug
Blood Coagulation
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Steps of Hemostasis
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Vascular Constriction
Vessel spasm constricts the vessel and reduces blood flow
Transient- minutes to hours
Vessel spasm is initiated by endothelial injury
Release endothelin-smooth muscle contraction
Vessel narrow-less bleeding
Local nervous reflexes and local humoral factors such as Thromboxane (TXA2) contribute to the vasoconstriction.
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Formation of Platelet Plug
Release of Thromboxane A2- a major enzymatic product of platelet activation, which cause vessel wall contraction
Von Willebrand is secreted by endothelial cells and binds to expose collagen fiber to the wound surface
Platelet through the interaction with bound Von Willebrand factor (Platelet adhesion)
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vWF released from the endothelium, binds to platelets receptors
Platelets adhere to the collagen fibers on the damaged vessel wall
Platelets become activated and release ADP and Thromboxane (TXA2)
ADP and TXA2 increase platelet aggregation
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Blood Clotting (Coagulation)
Coagulation cascades from Fibrin which wraps and strengthens platelet plug.
Form a “clot” or “Thrombus”
Involves a number of plasma proteins called “Clotting Factors”
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Requirements for Blood Clotting Process
Presence of platelets produced in the bone marrow
Von Willebrand factor generated by the vessel endothelium
Clotting factors synthesized in the liver using vitamin K
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Clotting Cascades
Terminal Steps in both pathways are the same:
Activation of factor X
Prothrombin activator converts prothrombin to thrombin
This interaction causes conversion of fibrinogen in fibrin stands that create the insoluble blood clot.
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Primary vs Secondary Hemostasis
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Regulation of Blood Coagulation
Antithrombin III inactivates coagulation factors and neutralizes thrombin
When antithrombin III is complexed with naturally occurring heparin, its action is accelerated, and provides protection against uncontrolled thrombus formation on the endothelial surface.
Protein C, a plasma protein, acts as an anticoagulant by inactivating factors V and VIII.
Protein S, another plasma protein, accelerates the action of protein C.
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Clot Retraction
20-60 minutes after clot formation
“Squeezing” serum from clot to bring edges of the broken blood vessel together
Clot shrink
Clot Dissolution
Plasma protein Plasminogen is trapped in the clot
Tissue Plasminogen Activator (tPA) is released from uninjured cells
tPA converts inactive Plasminogen to active “Plasmin” , which dissolves fibrin and allows platelet plug to dissolve.
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Summary Slide of Cascades
Hypercoagulability States
Increase the risk of clot formation in the arterial or venous circulations
Arterial thrombi are associated with conditions that produce turbulent blood flow and platelet adherence.
Venous thrombi are associated with conditions that cause stasis of blood flow with increased concentrations of coagulation factors.
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Hypercoagulability Associated with Increased Platelet Function
Atherosclerosis
Diabetes Mellitus
Smoking
Hyperlipidemia
Vessel Damage
Platelet Adherence
Thrombosis
Atherosclerotic plaques disturb blood flow, causing endothelial damage and promoting platelet adherence.
Smoking, elevated levels of blood lipids and cholesterol, hemodynamic stress, and diabetes mellitus predispose to vessel damage, platelet adherence, and eventual thrombosis.
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Hypercoagulability Associated with Increased Clotting Activity
Primary (Genetic) vs Secondary (Acquired)
Pregnancy, post-partum
Use of oral contraceptives
Postsurgical state
Immobility
Malignant disease
Congestive Heart Failure
Tissue Injury
Stasis of the Blood
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Virchow’s Triad
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Thrombocytosis
Platelet count: 150,000-400,000
Thrombocytosis:
Reactive (Secondary): due to other conditions
Essential Process (Primary): bone marrow disorder of the hematopoietic stem cells
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Negative Feedback Mechanism
Thrombopoietin-key hormone in the regulation of Megakaryocyte and platelet formation
In Plasma
Attached to receptors of platelets
Unbound-promote megakaryocyte proliferation
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Reactive (Secondary Thrombocytosis)
A disease state that stimulates thrombopoietin production
Common Causes (tissue damage)
Surgery
Infection
Cancer
Clinical Manifestations
Those of underlying disease
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Bleeding Disorders
Platelets Defects
Coagulation Defects
Platelet Defects
Thrombocytopenia
Circulating platelets < 150,000/ul
Causes
Decreased in platelet production
Aplastic anemia
Leukemia
Radiation therapy and some drugs (sulfa)
Increased sequestration in the spleen
Decreased platelet survival
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Immune Thrombocytopenic Purpura (ITP)
Autoimmune disorder
Platelet antibody formation and excess destruction of platelets
Primary or Idiopathic
Secondary—due to an underlying disorder
AIDS
SLE
Chronic Lymphocytic Leukemia
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Pathophysiology of ITP
Acute Vs Chronic
Acute ITP
Occurs in young children
Usually follows a viral infection
Sudden onset of petechiae
Self-limited disorder requiring no treatment
Chronic ITP
Occurs in adults
Insidious onset
Rarely follows a viral infection
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Immune Thrombocytopenic Purpura
Clinical Manifestations
Hx of bruising
Bleeding from gums
Epistaxis
Melena
Splenic enlargement may occur
Diagnosis
Severe Thrombocytopenia, platelets count<20,000
Exclusion of other causes
Test for platelet-bound antibodies (not specific)
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Thrombotic Thrombocytopenic Purpura
Rare disorder
Introduction of platelet-aggregating substances into the circulation
Deficiency of an enzyme (designated ADAMTS 13)
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Diseases of Coagulation or Hemostasis
Causes
Inherited disease
Von Willebrand Disease
Hemophilia A
Defective synthesis
Usually after injury or trauma
Liver cirrhosis
Increased consumptions of clotting factors
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Von Willebrand Disease
Most common hereditary bleeding disorder
Defects involving the factor VIII and vWF complex
Deficient (Type 1 and 3) or defective (Type 2) vWF
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Von Willebrand Disease
Clinical Manifestations
Epistaxis
GI bleed
Excessive menstrual flow
Bruising
Treatment
Replacement of vWF and Factor VIII
Desmopression acetate (DDAVP)
Stimulates release of vWF by endothelial cells.
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Hemophilia A
X-linked recessive disorder
Primarily affects males
Mutation in the factor VIII gene
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Disseminated Intravascular Coagulation (DIC)
Is considered an “acquired bleeding disorder”
Is not a disease entity but an event that can accompany various disease processes
Is an alteration in the blood clotting mechanism: abnormal acceleration of the coagulation cascade, resulting in thrombosis
As a result of the depletion of clotting factors, hemorrhage occurs simultaneously
Is a Paradoxical Clinical Presentation “clotting and hemorrhage”
Pathophysiology
In DIC, a systemic activation of the coagulation system simultaneously leads to thrombus formation (compromising blood supply to various organs) and exhaustion of platelets and coagulation factors (results in hemorrhage). This is a disruption of body homeostasis.
DIC Pathophysiology
Thrombosis-brief period of hypercoagulability
Coagulation cascade initiated-fibrin formation
Microthrombi deposit throughout the microcirculation
Fibrin deposits results in tissue ischemia, hypoxia, and necrosis
Multi-organ dysfunction
Fibrinolysis-period of hypocoagulability
Activates the complement system
Byproducts if fibrinolysis (fibrin/fibrin degradation products) interfere with platelets aggregation, fibrin polymerization and thrombin activity
Leads to Hemorrhage
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Pathologic Pathways
Extrinsic (endothelial)
Shock or trauma
Infections
Obstetric complications (eclampsia, placenta abruptio)
Malignancies
Intrinsic (blood vessel)
Infectious vasculitis
Vascular disorders
Intravascular hemolysis (hemolytic transfusion reactions)
Pancreatitis
Liver disease
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DIC Diagnostic Findings
Test
Platelet count
Fibrin degradation product (FDP)
Factor assay
Prothrombin time (PT)
Activated PTT
Thrombin time
Fibrinogen
D-dimer
Antithrombin
Abnormality
Decreased
Increased
Decreased
Prolonged
Prolonged
Prolonged
Decreased
Increased
Decreased
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Disorders of White Blood Cells
Leukocytes
Trigger inflammatory process and combat infections
Normal white blood cell (WBC) levels
5,000 to 10,000 cells/mL of blood
Leukocytosis vs. leukocytopenia
Most leukocyte disorders originate from deficiencies of leukocytes
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Neutrophils (1 of 2)
First responders to infection or inflammation
Neutrophilia (granulocytosis)
Increased number of neutrophils
Effect of too many immature cells: leukemoid reaction
Neutropenia
Decreased number of neutrophils
Decreased ability to fight infections
Multiple causes
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Neutrophils (2 of 2)
Clinical manifestations
Signs and symptoms of bacterial and fungal infections
Respiratory tract most common infection site
Diagnosis
Serum neutrophil levels
Determination of cause of neutropenia/neutrophilia
Treatment
Dependent on diagnosis
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Eosinophils and Basophils
Eosinophils
Control and augment inflammatory response
High with parasitic infections
Basophils
Release histamine and mediators
Basophilia can occur during hypersensitivity reactions
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Lymphocytes and Monocytes
Lymphocytes
Key cell involved in immune response
Lymphocytosis and lymphocytopenia can occur
Monocytes
Repeated low counts may signal bone marrow failure or leukemia
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Disorders of Red Blood Cells
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RBC Lab Values
Anemia
An abnormally low number of circulating red blood cells or level of hemoglobin, or both
Results in diminished oxygen-carrying capacity
Causes
Excessive loss or destruction of red blood cells
Deficient red blood cell production because of a lack of nutritional elements or bone marrow failure
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Classification of Anemia by MCV
Manifestations of Anemia
Impaired oxygen transport with the resulting compensatory mechanisms
Reduction in red cell indices and hemoglobin levels
Signs and symptoms associated with the pathologic process that is causing the anemia
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Sign and Symptoms
Tissue Hypoxia:
Fatigue, weakness, dyspnea, angina
Redistribution of the blood from cutaneous tissues or a lack of hemoglobin
Pallor of skin, mucous membranes. conjunctiva
Body Compensation
Tachycardia trying to increase cardiac output
Accelerated Erythropoiesis
Bone pain and sternal tenderness
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Sign and Symptoms
Hemolytic Anemias
Jaundice caused by increased levels of bilirubin
Aplastic Anemia
Petechiae and purpura are the result of reduced platelet function
Minute hemorrhagic spot and purplish area of the skin caused by small vessel bleeding
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Hemolytic Anemias
Occurs as a modification of the RBC structure and or life cycle.
Life cycle or Normal 90-120 days RBC life span may be shortened by a variety of disorders (ex. hemolysis) resulting in anemia if the bone marrow is unable to replace adequately the prematurely destroyed cells.
Hemolytic Anemia
Characterized by:
The premature destruction of red blood cells
The retention in the body of iron and the other products of hemoglobin destruction
An increase in erythropoiesis
Inherited vs Acquired
Intrinsic (Inherited) include defects of the red cell membrane.
Extrinsic (Acquired) caused by agents external to the red blood cell such as drugs, toxins, antibodies.
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Hemolytic Anemia
Inherited:
Sickle Cell Anemia
Thalassemia
Sickle Cells Disease
Affects 0.1-0.2% of Black Americans.
10% carry the “trait”
Two Forms:
Homozygous Form:
2 effected hemoglobin genes
80-95% of HgB is altered
Heterozygous Trait:
One abnormal HgB gene
40% of HgB is altered
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Sickle Cell Anemia
Most often affect people of African descent but also found in people of Mediterranean, Indian and Middle Eastern origin.
SCD Affects approx. 1-500 births (Blacks).
Results from a “point mutation” in the β-chain of hemoglobin.
Valine replaces glutamic acid
When Deoxygenated, the abnormal HgS aggregates and polymerizes to form a “gel”.
Distorts or “sickles” the RBC
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Factors that Exacerbate Sickling
Cold
Stress
Physical Exertion
Dehydration
Illness
?
Pain from vessel occlusion and hypoxia
Jaundice-hyperbilirubinemia-breakdown products of hemoglobin
Chest Syndrome: Atypical pneumonia resulting from pulmonary infarction
Sickle Cell Anemia
Diagnosis
Newborn screenings
Cord blood or heel stick samples are subhected to electrophoresis to separate the HbF from the small amount of HgA and HbS.
Treatment
Avoid stress
Prophylactic AB’s
Full immunizations
Chronic transfusions
Hydroxyurea:
Decreases synthesis of HbS.
Reduces pain
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Thalassemia
Genetic defect that results in defective synthesis of α or β chains of HgB.
α-Thalassemia
Asian populations
β – Thalassemia (Mediterranean)
Italy, Greece…Cooley’s anemia
Factors that Contribute to the Anemia in Thalasemia:
Reduce hemoglobin synthesis (hypochromic, microcytic)
Accumulation of the unaffected chain interferes with normal cell maturation and contributes to membrane changes that lead to hemolysis and anemia
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α-Thalassemia
Two pairs of genes control synthesis of the α-chain…
Severity depend upon the number of defective genes.
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Alpha-Thalassemia’s
“Alpha Trait”
1 defective gene
Asymptomatic
“Alpha Thalassemia minor”
Two defective genes
Mild hemolytic anemia
Hemoglobin H Disease”
Three defective genes
Chronic moderate hemolytic anemia
“Alpha-Thalassemia major”
All four alpha genes are defective
Fatal
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β-Thalassemia
More common than alpha form.
Results from multiple point mutations in the β-globin gene causing s defect in the β-chain synthesis
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β-Thalassemia
Thalassemia Minor:
1 defective gene
Mild-moderate anemia
Asymptomatic unless stressed
Thalassemia Major:
2 defective genes
Severe anemia
Chronic blood transfusions are needed
Massively increased erythropoiesis
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Anemia of Deficient Red cell Production
Iron Deficiency Anemia
Megaloblastic Anemia
Vitamin B12 Deficiency
Folic Acid Deficiency
Aplastic Anemia
Chronic Disease Anemia
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Dietary Deficiencies
Iron-Deficiency Anemia:
How does iron deficiency cause anemia? What patients are at the greatest risk for iron deficiency??
Folic Acid:
Necessary for RBC DNA synthesis & RBC maturation
May be deficient in ______, cancer
Vitamin B12 Deficiency:
Necessary for RBC DNA synthesis & RBC maturation
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Iron Deficiency Anemia
Most common cause of anemia
Results from dietary deficiency, loss of iron through bleeding, or increase demand
A decreased of iron leads to decreased hemoglobin synthesis and consequent impairment of oxygen delivery
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Nutritional Iron Balance
Intake
Dietary iron intake
Medicinal iron
Red cell transfusions
Injection of iron complexes
Excretion
Gastrointestinal bleeding
Menses
Other forms of bleeding
Iron Absorption
Dietary iron content is closely related to total caloric intake (approximately 6 mg of elemental iron per 1000 calories)
Average iron intake in an adult male is 15 mg/d with 6% absorption; average female, the daily intake is 11 mg/d with 12% absorption
Vegetarians are at an additional disadvantage because certain foodstuffs that include phytates and phosphates reduce iron absorption by about 50%
Takes place in the mucosa of the proximal small intestine
Absorption increase to 20% in iron-deficient persons
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Causes of Iron Deficiency
Increased demand for iron and/or hematopoiesis
Rapid growth in infancy or adolescence
Pregnancy
Erythropoietin therapy
Increased iron loss
Chronic blood loss
Menses
Acute blood loss
Blood donation
Phlebotomy as treatment for polycythemia vera
Decreased iron intake or absorption
Inadequate diet
Malabsorption from disease (sprue, Crohn's disease)
Malabsorption from surgery (post-gastrectomy)
Acute or chronic inflammation
Labs
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Treatment of Iron Deficiency
Oral Iron Therapy (Mild cases)
Ferrous sulfate
Ferrous fumarate
Ferrous gluconate
Parenteral Iron (Severe cases)
Blood Transfusion for life-threatening bleeding!!!
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B12 Deficiency (Macrocytic Anemia)
Due to impaired DNA synthesis
Causes
Inadequate intake (vegetarians)-rare
Malabsorption
Defective release of cobalamin from food
Partial gastrectomy
Inadequate production of intrinsic factors (IF)
Pernicious anemia; total gastrectomy
Disorders of Terminal Ileum
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Clinical Manifestations Vitamin B12 Deficiency
Hematologic
Macrocytic Anemia
Gastrointestinal
Glossitis
Anorexia
Diarrhea
Neurologic (found in 3/4th of individuals with pernicious anemia)
Numbness and paresthesia in the extremities, Weakness, Ataxia
Disturbances of mentation
Mild irritability and forgetfulness to severe dementia or frank psychosis.
Demyelination, Axonal degeneration, and then Neuronal death
Last stage is irreversible
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Pernicious Anemia
Most common cause of cobalamin deficiency
Caused by the absence of IF
Atrophy of the mucosa
Autoimmune destruction of parietal cells
Seen in individuals of northern European descent and African Americans
Men and women are equally affected
Disease of the elderly, the average patient presenting near age 60
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Diagnosis of Vitamin B12 Deficiency
Macrocytosis (MCV > 115
Peripheral blood smear
Cobalamin levels
Homocysteine levels -Increased
Methylmalonic acid (MMA) – increased
Antibody testing – Anti IF
Schilling Test – old replaced with newer labs!
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Treatment of Vitamin B12 Deficiency
Replacement therapy
Parenteral treatment given weekly intramuscularly for 8 weeks, followed by intramuscularly every month for the rest of the patient's life.
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Folate Deficiency
More often malnourished than those with cobalamin deficiency
Gastrointestinal manifestations
More widespread and more severe than those of pernicious anemia
Diarrhea is often present
Cheilosis
Glossitis
Neurologic abnormalities do not occur
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Stages of folate deficiency
Negative folate balance (decreased serum folate)
Decreased RBC folate levels and hypersegmented neutrophils
Macroovalocytes (oval shaped erythrocyte), increased MCV, and decreased hemoglobin
Diagnosis of folate deficiency
Peripheral blood and bone marrow biopsy look exactly like B12 deficiency
Plasma folate <3 ng/ml—fluctuates with recent dietary intake
RBC folate—more reliable of tissue stores <140 ng/ml
MMA is normal, homocysteine is increased.
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Treatment of folate deficiency
Oral replacement therapy
Folate prophylaxis
Women planning pregnancy are advised to take 400 g folic acid daily before conception and until 12 weeks of pregnancy to prevent neural-tube defects (5 mg/day for women with a previous affected pregnancy)
Folate fortification of cereal grains at 1·4 mg/kg has been made mandatory in the USA as an additional method of improving the folate status of the population.
Prophylactic folate is also recommended in other states of increased demand such as long-term hemodialysis and chronic hemolytic disorders
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Aplastic Anemia
Disorder of the bone marrow stem cells that results in a reduction of:
Red Blood Cells
White Blood Cells
Platelets
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Bone Marrow
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Aplastic Anemia
Causes
High dose of radiation
Chemical
Toxins
Chemotherapy
Infections
Mononucleosis
AIDS
Treatment
Bone marrow transplantation
Peripheral blood transplantation
Hematopoietic stimulants
Immunosuppressive therapy
Antibiotics
