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RED BLOOD CELL

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					RED BLOOD CELL DISORDERS

Cell lineage
   - Pluripotent  multipotent (myeloid & lymphoid)
          o Myeloid  RBCs, platelets, neutrophils, basophils, eosinophils,
             monocytes
          o Lymphoid  B & T lymphocytes

Oxygen-Hgb dissociation curve
   -   The amount of oxygen bound to the hemoglobin at any time is related, in
       large part, to the partial pressure of oxygen to which the hemoglobin is
       exposed. In the lungs, at the alveolar-capillary interface, the partial pressure
       of oxygen is typically high, and therefore the oxygen binds readily to
       hemoglobin that is present. As the blood circulates to other body tissue in
       which the partial pressure of oxygen is less, the hemoglobin releases the
       oxygen into the tissue because the hemoglobin cannot maintain its full bound
       capacity of oxygen in the presence of lower oxygen partial pressures.
   -   Effects of 2,3-DPG. 2,3-diphosphoglycerate, or 2,3-DPG, is an
       organophosphate, which are created in erythrocytes during glycolysis. The
       production of 2,3-DPG is likely an important adaptive mechanism, because
       the production increases for several conditions in the presence of diminished
       peripheral tissue O2 availability, such as hypoxemia, chronic lung disease,
       anemia, and congestive heart failure, among others. High levels of 2,3-DPG
       shift the curve to the right, while low levels of 2,3-DPG cause a leftward shift,
       seen in states such as septic shock and hypophosphatemia.
   -   http://www.ventworld.com/resources/oxydisso/dissoc.html#under
       stand

ANEMIA FROM BLOOD LOSS
  - ACUTE
       o Less than 5-7 days
       o N/N, Hct stays the same initially  after 48 hrs, Hct dec due to
         inc in fluid volume faster than inc in RBCs
       o See inc EPO
       o Don’t see an inc retic ct
  - CHRONIC
       o Most commonly due to GI bleeds
       o Leads to IDA with dec Hct
       o Don’t see an inc retic ?????

ANEMIA FROM INCREASED RATE OF DESTRUCTION
  - HEMOLYTIC ANEMIA
       O INTRAVASCULAR
             Causes
                  Mechanical destruction
          Complement induced damage
      Consequences
          Accumulation of Hgb by-products
              o Hemosidinuria
                      Due to iron released from RBCs
              o Hemoglobinuria
                      Due to Hgb released from RBCs
              o Hemoglobinemia
                      Due to Hgb released from RBCs
                      Leads to dec haptoglobin
          Inc er ythropoiesis  inc retics
          Jaundice
              o Due to bilirubin released from RBCs
          Abnormally colored urine
              o Due to hemosidinuria and hemoglobinuria
     Types
          PNH – Paroxysmal Nocturnal Hemoglobinuria
O EXTRAVASCULAR
     Causes
          Defective RBCs
     Consequences
          Inc EPO
              o Due to hypoxia in kidney
          Inc normoblasts
          Inc retics
          Hepatosplenomegaly
              o Due to extramedullary hematopoiesis
          Inc volume of bone marrow
              o Frontal bossing
              o Chipmunk cheeks
          Increased bilirubin
              o Jaundice
              o Pigmented gallstones
          Hemosiderosis
              o Can lead to hemochromatosis
O HEREDITARY SPHEROCYTOSIS
     Causes
          Autosomal dominant defect in spectrin  spherical
            RBCs
     Consequences
          Intravascular & extravascular hemolysis
          Clubbing
          Splenomegaly
          Hemolytic crisis
           Aplastic crisis
O GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY
      Causes
           X-linked deficiency of G6PD
               o G6PD maintains store of reduced glutathione 
                  antioxidant
      Consequences
           Intravascular & extravascular hemolysis
           Free radical damage to RBCs
               o Heinz bodies  bite cells
      Types
           Type A form
               o Still have 10% normal enzyme
               o Hemolytic crisis due to inc free radicals (drugs:
                  primaquinine)
           Mediterranean form
               o Aggravated by infections (ex. hepatitis,
                  pneumonia)
               o Associated with Favism
O SICKLE CELL DISEASE
      Causes
           Point mutation in coding of beta chain  Hgb S
           Low oxygen tension  sickling of RBCs
      Consequences
           Extravascular hemolysis
           Capillary obstruction  microinfarctions
               o Stroke
               o Blindness
               o Lung infarcts  pneumonia
               o Kidney infarcts
               o GI problems
               o Initially splenomegaly due to extravascular
                  hemolysis but eventually microinfarctions 
                  destruction of spleen tissue  small spleen 
                  “autosplenectomy”  osteomyelitis
                  (inflammation of the bone marrow due to
                  staph infection)
               o Damage to bone  infections
           Priapism
           Iron overload  organ problems
           Aplastic crisis
               o Often from parvovirus B-19 infection of
                  marrow
o THALASSEMIA
   -thalassemia
        Causes
             o Deleted genes responsible for integrity of 
                chain of Hgb
                    1 gene deletion = silent carrier
                    2 gene deletions = -thalassemia trait
                    3 gene deletions = -thalassemia
                      (minor)
                          AKA Hgb H disease
                    4 gene deletions = -thalassemia
                      (major)
                          Not compatible with life
                    Will effect
                          Hgb A (2,2)
                          Hgb A2 (2,2)
                    African form due to gene deletion at one
                      locus on both chromosome 16’s
                    Asian form due to gene deletion at two
                      loci on one chromosome 16
             o Too many beta chains produced by comparison
        Consequences
             o Ineffective erythropoiesis
                    Macrophages in bone marrow destroy
                      RBCs before they are released
                    Some RBCs get out and are destroyed by
                      the spleen
                          Splenomegaly leads to
                             sequestering of platelets and
                             neutrophils  pancytopenia
                                o More susceptible to infection
                                o Bleeding problems
             o Microcytic hypochromic anemia
             o Decreased Hgb content  increased surface
                area of membrane to volume ratio  target
                cells
   Beta thalassemia
        Types
             o Major
                    Homoxygotic form
                    50 different mutations
                    AKA Cooley’s Anemia
             o Minor
                    Heterozygotic form
        Presentation
              o Newborns still have hemoglobin F (2 & 2), so
                 -thalassemia will not appear until hemoglobin
                 A appears
          Causes
              o Mutated gene for beta chain of Hgb
                     B0 = mutation causing zero beta chain
                        production
                     B+ = mutation causing decrease in beta
                        chain production
                     B0 / B0 = incompatible with life
                     B+ / B0 = thalassemia major
                     B0 / B OR B+/ B = thalassemia minor
                            AKA thalassemia trait
              o Insufficient beta chains  alpha chains build
                 up in cytoplasm  S/Sx of dz
          Consequences
              o Ineffective erythropoiesis
                     Macrophages in bone marrow destroy
                        RBCs before they are released
                     Some RBCs get out and are destroyed by
                        the spleen
o TRAUMA TO RBCs
     Microangioplastic hemolytic anemia
          Cause
              o Formation of microthrombi (platelet and fibrin
                 aggregates)
              o Associated with
                     DIC
                     TTP
                     HUS
                            Microthrombi  renal failure
          Consequences
              o Jaundice
              o Dark colored urine
                     Hemosiderin
                     Hemoglobin
                     Methemoglobin
              o Low serum haptoglobin
                     Intravascular hemolysis
                     In severe cases of extravascular
                        hemolysis – free Hgb enters blood
                        stream through spleen
              o Hemosiderosis
                        o Methemoglobin – Hgb with ferric iron instead
                           of ferrous iron and it cannot carry oxygen
                                Most in the blood stream, not in the
                                  RBCs
                        o Schistocytes
              Macroangioplastic hemolytic anemia
  -   AUTOIMMUNE HEMOLYTIC ANEMIA
        o Warm Ab type
              Cause
                    IgG Ab to RBCs, platelets, and neutrophils
                    Ab-Ag reactions occur in warmer blood  see
                     hemolysis in blood vessels closer to the core
                    Associated with
                        o CLL
                        o SLE
                        o Ulcerative colitis
                        o Rh factor babies
                                The Abs produced are not just Rh
                                  specific, sometimes they are specific for
                                  other types of cell membrane structures
              Consequence
        o Cold Ab type
              Cause
                    IgM Ab to RBCs
                    Associated with
                        o Non-hodgkins lymphoma
                                Esp elderly
                        o Mycoplasma pneumonia (primary atypical
                           pneumonia)
                                Esp young pts
                        o Infectious mono
                                Esp young pts
              Consequence

ANEMIA FROM IMPAIRED PRODUCTION
  - MEGALOBLASTIC ANEMIA
       o Types
             Vitamin B12 deficiency
                  Cause
                      o Decreased synthesis of purines  decreased
                          DNA synthesis
                      o Low intake (vegan diet)
                      o Crohn’s disease
                      o Chronic pancreatitis
                       R binding protein in the saliva binds to
                        Vit B12  R binding protein protects Vit
                        B12 from destruction by stomach acid 
                        trypsin and chymotrypsin (enzymes
                        produced in pancreas) are needed to
                        digest R binding protein and release Vit
                        B12 for absorption
             o Tape worm
        Consequence
             o See consequences of pernicious anemia
   Pernicious anemia
        Cause
             o Ab to parietal cell or intrinsic factor (IF) 
                 decreased levels of IF  impaired absorption
                 of Vit B12
             o Decreased synthesis of purines  decreased
                 DNA synthesis
        Consequences
             o Neurological abnormalities
                     Loss of myelin in the dorsal columns and
                        the lateral corticospinal tracts
                            Dorsal column = position &
                               vibration
                            Lateral corticospinal tract = motor
                     Symptoms
                            Numbness & tingling
                            Loss of proprioception in the lower
                               extremities
                            Ataxia
                            B/L spastic paralysis – often only in
                               the upper extremities
   Folate deficiency
        Causes
             o Decreased synthesis of purines  decreased
                 DNA synthesis
             o Alcoholism  depletes storage sites
             o Poor diet
             o Folate antagonists
                     Chemotherapy
        Consequence
             o Glossitis
             o Nausea
             o Vomiting
             o Indigestion
                         o Gas
                         o Diarrhea
  -   IRON DEFICIENCY ANEMIA
        o Absorption of Iron
              Heme iron Fe2+ = iron in Hgb and myoglobin
                    25% is absorbed
                    Source = meat
              Non-heme iron Fe3+ = iron in metHgb
                    1% is absorbed
                    Source = vegetables
                    Addition of Vit C increases absorption
        o Cause
              Blood loss
                    GI bleed
                         o Peptic ulcers
                         o Colon CA
                    Severe hemorrhage
                    Excessive menses
              Decreased intake
              Decreased absorption
              Increased demand
                    Pregnancy
                    Lactation
        o Consequence
              Microcytic hypochromic RBCs
              Brittle nails
              Pica
              Headache
              Blue tinge to sclera
  -   APLASTIC ANEMIA
        o Cause
              Disruption of hematopoiesis due to
                    Chemicals
                    Drugs
                    Environmental exposure
                    Virus
                         o Parvovirus
                         o Hep C
        o Consequence
              Pancytopenia
              WBCs and RBCs are larger than normal
              Neutrophils will look old (5-6 lobes)

POLYCYTHEMIA
-   ABSOLUTE = # of RBCs is increased
      o Primary = POLYCYTHEMIA VERA
            Cause
                 Myeloproliferative disorder that affects the trilineage
                   stem cells
                      o Chronic myelogenous leukemia
                      o Primary thrombocythemia
                 EPO is low due to feedback inhibition
            Consequence
                 Hypervolemia  venous collection  cyanosis 
                   organ infarction (brain & heart)
                 Hyperviscosity  hepatic vein thrombosis =
                   extremely fatal
                      o More serious than portal thrombosis b/c liver
                        has collateral blood supply
                 Hyperuricemia
                      o Increased activity in the bone marrow  rapid
                        turnover of cells  death of cells  DNA
                        released  catabolism of purines  excess uric
                        acid
                      o Increased incidence of
                             Kidney stones
                             Gout
                             Kidney damage
                 Histaminemia
                      o Increased basophils  increased release of
                        histamine
                      o Increased risk of peptic ulcers
                      o Itching
                      o Vasodilation
                 Prone to bleeding
                 Bone marrow failure due to excessive myelofibrosis
                    decreased Hct
      o Secondary
            Cause
                 Hypoxia  increased EPO secretion
                      o Low PaO2 (hypoxemia)  Low SaO2 
                        increased kidney production of EPO
                      o Increased altitude
                      o Tetrology of Fallot
                      o Lung disease
                             Asthma
                             Emphysema
                             Chronic bronchitis
                              Black lung disease
                        o CHF
                        o Left shifted oxygen dissociation curve
                              Alkaline conditions
                              Hypothermia
                              Sleep apnea
                              Pickwickian syndrome
                              CO poisoning
                    Tumors  increased EPO secretion
                        o Renal cell carcinoma
              Consequence
                    Same as primary
  -   RELATIVE = plasma volume is decreased  hemoconcentration
        o Cause
              Burns
              Shock
              Dehydration
                    Severe diarrhea
        o Consequence
              ?

BLEEDING DISORDERS
  - VASCULAR FRAGILITY
  - THROMBOCYTOPENIA
       o Isoimmune type
       o ITP
       o TTP
       o TTP-HUS
  - DEFECTIVE BLOOD PLATELETS
  - ABNORMAL CLOTTING FACTORS
       o Hemophilia
       o Von Willebrand
  - DIC
  - THROMBOCYTHEMIA

				
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posted:11/2/2011
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