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94 Cards in this Set

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What are the components of the CBC (complete blood count)?
-hemoglobin (Hb)
-hematocrit (Hct)
-MCV (mean corpuscular volume)
-MCHC (mean corpuscular Hb concentration)
-RDW (red cell distribution width)
-total white cells
Definition of anemia.
A reduction of the whole blood hemoglobin concentration below the reference range for age and sex.
Hemoglobin in CBC
-Hb concentration in whole blood in g/dL
-normal: male 14-17; female 12-15
Hematocrit in CBC
-(PCV=packed cell volume)
-volume of RBC's per volume of whole blood
-measured as %
normal: male 41-50%, female 36-44%
-general rule: Hct = 3xHb
MCV in CBC
-Mean Corpuscular Volume
-average volume/size of each RBC
-helps classify anemia into microcytic, normocytic, macrocytic
MCHC in CBC
-Mean Corpuscular Hemoglobin Concentration
-average Hb concentration in EACH RBC
-reported as g/dL
-(one of the least important)
-can give an idea of how red the center of the RBC is
What in the CBC is low in Iron Deficiency?
MCHC
What in the CBC is high in Spherocytosis?
MCHC
What conditions have a low and high MCHC in the CBC?
low MCHC: iron deficiency
high MCHC: sphreocytosis
RDW in CBC
-Red Cell Distribution
-reflects VARIATION IN SIZE of RBC
-only important to know that it is INCREASED in iron deficiency anemia
What component of the CBC is increased in Iron Deficiency Anemia?
RDW
What is erythropoeisis and what does it depend on?
-production of RBCs in bone marrow
-depends on erythropoieten (EPO) from the kidneys
What are some stimuli for EPO to be released?
-hypoxemia
-low Hb
-left-shifted O2 binding curve
-high altitude
-anything that causes low O2 in tissues
What are markers of erythropoeisis?
reticulocytes
What are reticulocytes?
non-nucleated RBC precursor still containing some ribosomal RNA
What is the reticulocyte index and what does a high or a low RI indicate?
RI = reticulocyte count (%) x (pt's Hct/normal Hct(45))
-corrects for already low RBC levels = corrected reticulocyte count
-high RI - appropriate bone marrow response to anemia (hemolytic anemia, hemorrhage)
-high RI - inappropriate marrow response to anemia (Fe deficiency, aplastic anemia, B12/folate deficiency, other marrow defects)
What are some microcytic anemias and what are they caused by?
-iron deficiency
-anemia of chronic disease (ACD)
-thalassemia (alpha and beta)
-sideroblastic anemia

-various defects in the synthesis of Hb
Irony Deficiency anemia
-microcytic anemia
-most common type of anemia
-decreased synthesis of HEME secondary to LOW IRON STORES
What are some causes of low iron stores leading to iron deficiency anemia?
-blood loss (GI - NSAID use or GU - women of reproductive age)
-increased utilization - pregnancy, lactation, children
-decreased intake - infants (breast milkd) and children
-decreased absorption - celiac sprue
What are the lab values with iron deficiency anemia?
decreased MCV, Fe, Fe Sat%, Ferritin
increased TIBC, RDW
What does SERUM FERRITIN measure?
-FERRITIN is the primary soluble iron storage protein - binds to Fe
-serum levels correlate with levels stored by macrophages in bone marrow
What does SERUM IRON measure?
-represents iron BOUND TO TRANSFERRIN, an iron binding protein made in liver
What does TIBC measure?
-serum Total Iron Binding Capacity
-correlates with concentration of TRANSFERRIN
-reflection of how much transferrin is unbound
What does Iron % saturation measure?
-Transferrin Saturation %
-represents % binding sites on transferrin occupied by iron
-simply (serum iron/TIBC) x 100
What is RDW?
-red cell distribution width
What are some Clinical Symptoms of Iron deficient anemia and how do you treat it?
common: fatigue, pallor, history of menorrhagia, melena (black tarry stools), GI upset, peptic ulcer disease risk factors (NSAID use)
rare: glossitis (inflammation of tongue), spoon like nails (koilonychia)
-treat underlying cause
-give oral iron (ferrous sulfate)
What are the possible causes of Anemia of Chronic Disease?
-microcytic anemia - decreased synthesis of HEME
-causes: chronic inflammatory conditions, malignancy, alcoholism, hospitalized patients
What is the pathogenesis of Anemia of Chronic Disease?
-hepcidin, an acute phase reactant, is released by the liver, enters cells and prevents the release of iron to transferrin, therefore FERRITIN SYNTHESIS and MARROW MACROPHAGE IRON STORES are INCREASED (the body is 'saving' iron inappropriately)
What are the important Lab values of Anemia of Chronic Disease.
decreased MCV, Fe, TIBC, Fe Sat%, RI
increased ferritin
What lab values differ in Iron Deficiency anemia and Anemia of Chronic Disease?
TIBC increased in Iron Deficiency Anemia and decreased in Anemia of Chronic Disease.
FERRITIN decreased in Iron Deficiency Anemia and increased in Anemia of Chronic Disease
-SOLUBLE TRANSFERRIN RECEPTORS - elevated in iron deficiency anemia
Thalassemias
-autosomal recessive disorders
-microcytic anemia
-QUANTITATIVE defects in GLOBIN chains
-2 types - alpha and beta
Alpha-thalassemia
-microcytic anemia
-Southeast Asian/African American
-DECREASE in ALPHA-GLOBIN CHAIN SYNTHESIS due to GENE DELETIONS (4 genes in control of alpha chains)
-1 gene deleted: silent carrier
-2 gene deleted: alpha-thal trait, mild
-3 gene deleted: HbH - severe hemolytic anemia, HbH ->Heinz bodies
-4 genes deleted: Hb Bart - incompatible with life
How do Heinz Bodies form?
-oxidation of iron from ferrous to ferric form leads to denature Hb precipitation and damage to RBC membrane. - leads to formation of bite cells
-HbH (3 gene deletions of alpha-globin chain) is unstable and precipitates to form Heinz Bodies
bBeta-thalassemia
-most common thalassemias
-Greeks, Italians (Mediteranean), African Americans
-DECREASE in BETA-GLOBIN chain SYNTHESIS due to SPLICING DEFECTS or NONSENSE MUTATION
-may be fully absent or partially defective: B-Thal minor (B/B-) - not tx; B-Thal major (BO/BO) - severe, need transfusion w/ Fe chelating to prevent Fe overload
-Basophilic Stippling - precipitation of globin chains (similar to Heinz bodies)
Macrocytic Anemias
B12 deficiency
folate deficiency
What is the mechanism for B12 and folate deficiency?
-block in cell division --> delayed nuclear maturation (condensation)
-cytoplasm grows via RNA which is not affected, so cytoplasm continues to expand
-results is large cells
-IMPAIRED DNA SYNTHESIS (B12 and folate needed to convert homocysteine to methionine by methionine synthetase and B12 needed to convert MMA/MMCoA to succinyl CoA by MMCoA mutase)
How does B12 normally work?
B12 binds to intrinsic factor (IF) released by parietal cells in the stomach and is then reabsorbed in the terminal ileum
what are some causes of B12 deficiency?
-decreased intake: pure vegan diet
-malabsorption: pernicious anemia (autoimmune destruction of parietal cells -> atrophic gastritis and achlorhydia) or Chron's Disease or Celiac Disease (involving the distal ileum)
What do the cells look like in B12 deficiency?
RBCs - ovaloctyes - large oval-shaped
PMNs - hypersegmented
Clinical features of B12 deficiency
-signs/symptoms of anemia
-achlorhydia and atrophic gastritis in pernicious anemia - autoimmune destruction; associated with vitiligo (autoimmune phenomenon where desructtion of melanocytes were they lose pigment), diabetes, etc
-smooth tongue - swelling of tongue (glossitis)
-neuro defects due to buildup of MMA: dementia, SACD, irreversible in some cases
SACD
-Subacute Combined Degeneration
-deterioration of both the posterior (vibration, proprioception) and lateral columns of the spinal cord; affects both sensory and motor tracts
vitiligo
autoimmune phenomenon causing destruction of melanocytes where they lose pigment
B12 deficiency Lab features
decreased B12, may have pancytopenia, hypersegmented PMNs (>5 lobes), increased ovalocytes, increased MCV, increased homocysteine, increased MMA (more specific than B12 and homocysteine)
-positive Schilling Test
pancytopenia
decrease in all components of CBC (DNA impairment affects WBC and platelets too)
folate deficiency causes
-decreased intake: malnutrition, chronic alcoholics, goats milk
-malabsorption - celiac disease
-drugs - 5-FU, methotrexate (DHF reducatse inhibition)
-increased utilization - pregnancy/lacation, malignancy
where is folate absorbed?
jejunum and proximal ileum
How long do folate body stores last?
3 months
How long do B12 body stores last/
3 years
Folate deficiency's labs and clinical
similar to B12 except:
-no neuro defects
-normal MMA levels
-may 'mask' B12 deficiency in elderly (difference in body storage supply)
-neural tube defects
Treatment of B12/Folate deficiency
-give IV or oral B12 (cyanocobalamin) depending on severity
-give oral Folic Acid
-treat underlying cause of deficiency
-send to neurologist if B12 deficient
aplastic anemia
-normocytic, RI<3%, decrease in marrow production
-failure or destruction of multipotent myeloid (in marrow) stem cells leading to inadequate production or release of differentiated cell lines
causes of aplastic anemia
-50-70% idiopathic
-DRUGS - most common known cause
-autoimmune
-viral infections
-toxic chemicals
-radiation
-thymoma assocation
Aplastic anemia clinical/lab findings and treatment
-fatigue, malaise, fever, mucosal bleeding, petechiae
-pancytopenia (decreased WBC, platelets, Hb/Hct, RI)
-HYPOcellular bone marrow with FATTY infiltrate
-tx: remove offending agnets, give immunosuppressants, G-CSF, GM-CSF, BMT
hemolysis
destruction of RBCs
-due to intrinsic defects (ex: bad membrane) or extrinsic factors (ex: mechanic valve or antibodies)
-may occur directly in BV (contents spill into blood) or in extravascular sites (liver, spleen)
General lab findings associated with hemolysis
-increased urine Hb
-increased serum lactate dehydrogenase (LDH is abundant in RBCs) - intravascular
-increased unconjugated bilirubin -> jaundice
-decreased serum Hb/Hct
-decreased serum haptoglobin - intravascular (binds up the free serum Hb)
-increased RI b/c cells being destroyed
What does haptoglobin do?
binds Hb in serum
schistocytes
fragments of RBCs chewed up
sphereocytes
membrane defect
What are these?
schistocytes
What does this depict?
spherocytes
Hereditary Spherocytosis
-autosomal dominant normocytic anemia w/ RI > 3% - marrow working fine
-defect of RBC membrane:
-ANKYRIN, BAND2, SPECTRIN, BAND3 defects in
-increased membrane permeability = osmotic fragility
-SPLEEN sees this as a bad thing and TARGETS the RBCs for DESTRUCTION by macrophages -> this extravascular hemolysis leads to SPLENOMEGALY
Hereditary Spherocytosis Labs/Clinical and treatment
-decreased Hb/Hct, increased MCHC, RDW, bilirubin, RI
-anemia, jaundice, splenomegaly
-tx: supportive, RBC transfusion, TAKE OUT the SPLEEN after age 6 (sphreocytes still seen in blodd, but Howell-Jolly bodies now present)
What are these called and what are they?
Howell-Jolly bodies
-these are RBCs with DNA fragments that are normally filtered out by the SPLEEN...think spleen or no spleen with HJ
Sickle Cell Anemia features
-most common hemoglobinopathy in African Americans
-normocytic anemia
-autosomal recessive (HbAS - sickle cell trait - no anemia/carrier; HbSS - sickle cell anemia - homozygous)
-protective against P. Falciparum malaria
Pathogenesis of Sickle Cell Anemia
missense mutation: substitution of Val for Glu at 6th position of beta-globin chain
-causes 'sickling' via LOW OXYGEN
Describe sickling.
-HbS molecules aggregate and polymerize -> RBCs assume 'sickle' shape and become rigid -> VESSELS are OCCLUSION and spleen overwhelmed with filtering -> SPLENOMEGALY (large spleen) -> AUTOINFARCTION (smaller spleen)
What are the major precipitators of sickling?
-acidosis (right shift in O2-Hb curve - less oxygenated Hb)
-volume depletion - increased deoxygenated Hb concentration
-hypoxemia (less oxygenated Hb)
LOW OXYGEN CAUSES SICKLING
Clinical Features of sickle cell anemia
-anemia, pallor, jaundice (hemolysis), lethargy, bone pain
-DACTYLITIS - painful swelling of hands/feet due to bone infarct (most common presentaiton in infants)
-ACUTE CHEST SYNDROME
-SPLENIC DYSFUNCTION - enlraged in childhood -> fibroses and shrinkage by adult; HJ bodies on peripheral smear; increased susceptibility to encapsulated bacteria (N. meningititis, H. influenzae, and S pneumoniae) -vaccines
-Renal dysfunction
-PRIAPISM - painful, persistent erection
-SALMONELLA OSTEOMYELITIS
acute chest syndrome
-clinical feature of sickle cell anemia
-vaso-occlusion of pulmonary capillaries
-chest pain, lung infiltrates, hypoxemia
-most common cause of death in adults with sickle cell anemia
Sickle Cell Anemia Diagnosis and Treatment
-CBC: anemia, RI > 3%
-peripheral smear: sickle cells, target cells and HJ bodies
-Hb electrophoresis to detect HbAS, HbSS
HPLC, new born screening
-tx: ANALGESIA, HYDRATION, OXYGEN, +/- antibiotics, HYDROXYUREA (increases production of HbF (fetal Hb is protective)), blood transfusion as needed, splenectomy as needed, BMT
What disease does this show?
sickle cell anemia
What are the normocytic anemias?
-low RI - defective bone marrow production: hemolytic anemias: aplastic anemia
-high RI - hereditary spherocytosis, sickle cell anemia
Normal CBC values
-WBC - 5,000-10,000/uL
-Hb - 12-17g/dL
-Hct - 37-50%
-platelets - 150,000-350,000/uL
-normal BM biopsy - low power
~40-60% of BM area is made up of FAT (% increases with age)
-variety of cell populations
-normocellular BM aspirate - high power
-mixed cellularity
-arrows indicate maturing forms of granulocytes (neutrophils, eosinophils, basophils) - HETEROGENEOUS POPULATION OF CELL TYPES
1) granulocytes - pink granular cytoplasm, multi-lobed nucleus
2) dense round cells at 7:30 are erythroid precursors
3) large cells are lymphocyte precursors
4) no megakaryocytes seen in this image
What are the three main external sources that can cause DNA damage leading to neoplasia?
chemicals, radiation, viruses
Where do mutations occur that lead to the possible development of neoplasia?
-activation of growth-promoting PROTO-ONCOGENES
-inactivation of TUMOR SUPPRESSOR genes
-alterations of genes that regulate APOPTOSIS
What is an "initiated cell?"
-A cell that expresses altered gene products and loss of regulatory gene products (expresses activated oncogenes or inactivated tumor suppressor genes)
-susceptible to clonal expansion and is able to acquire new mutations that can give rise to malignancy (could take many years)
-not malignant or neoplastic, just 'changed from normal'
Where do CCS drugs act and with what are they most effective?
-Cell Cycle Specific (phase specific)
-work on rapidly dividing cells
-most effective in hematologic and solid tumors with HIGH GROWTH FRACTION
Where do CCNS drugs act and with what are they most effective?
-Cell Cycle Non-Specific
-act on dividing as well as resting cells (G0 state)
-effective in LOW GROWTH FRACTION, as well as HIGH GROWTH FRACTION solid tumors
What is growth fraction?
the ratio of proliferating cells to cells in G0 (resting phase where cell is NOT dividing).
-high growth fraction - tissue with a large % of proliferating cells and few cells in G0
-low growth fraction - tissue composed mostly of cells in G0
What are some examples of CCS drug types?
-antimetabolites
-vinca alkaloids
-etoposide
-bleomycin peptide antibiotics
What are some examples of CCNS drug types?
-alkylating agents
-antibiotics
-cisplatin
-nitrosoureas
What is significant about the growth fraction and DNA index with regard to chemo?
The higher the growth fraction and higher DNA index (amount of cells in S phase), the more chemosensitive the tumors will be.
What types of tumors are chemosensitive vs nonchemosensitive?
-chemosensitive - embryonal and malignant lymphomas (rapidly dividing, responsive to CCS and CCNS)
-nonchemosensitive - adenocarcinomas (low growth fraction, only responsive to CCNS)
What is the Log-Kill Hypothesis?
-chemotherapeutic agents follow FIRST ORDER KINETICS
-a CONSTANT % or fraction of cells are killed rather than a constant number of cells, following each does of chemotherapy
Palliative chemotherapy
-INFREQUENT scheduling of LOW DOSE treatment with a LATE start
-prolongs survival but DOES NOT CURE the patient
Curative Chemotherapy (disseminated cancer)
-INCREASED FREQUENCY of treatment, with ADEQUATE DOSING, and an EARLIER START
Curative chemotherapy (solid tumor)
-early SURGICAL REMOVAL of the primary tumor decreases the tumor burden
-chemotherapy will remove persistent secondary tumors, and the total duration of therapy is increased as compared to chemo alone
-cuts down on the rounds of chemo
What are the advantages of Combination Chemotherapy?
-decreased risk of drug resistance
-increased cancer cell kill due to different mechanisms of action of the drugs
-reduced injury to normal cells by use of drugs with different toxicities
What are some mechanisms that cells become resistant to chemo drugs?
-altered affinity of target enzyme
-DNA repair mechanisms
-excessive degradation of drug
-altered DRUG TRANSPORT
What is the classic example of antineoplastic drug resistance?
P-glycoprotein
-ATP-binding cassette (ABC) trasnsporter
-encoded by MDR1gene (Multi Drug Resistance)
-INCREASED EFFLUX of selected antineoplastic DRUG
What are some of the toxicities of antineoplastic drugs?
-bone marrow - thrombocytopenia, anemia, leukopenia
-GI - oral or intestinal ulcers
-hair follicles - alopecia
-gonads - menstrual irregularities (incl. premature menarche), impaired spermatogenesis
-wounds - impaired healing
-fetus - teratogenic
What are the neoplastic treatment modalities?
surgery, radiotherapy - for local disease
chemotherapy - systemic spread of disease