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306 Cards in this Set
- Front
- Back
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3 types of lab tests
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1. Screening
2. Diagnostic 3. Monitoring |
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SDM lab tests
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Screening = asymptomatic, find new dz
Diagnostic = assist d/dx Monitoring = monitor progress of known/eval. progress of disease |
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Variables that affect lab results (4)
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Biologic
Pre-analytic Analytic Post-analytic |
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BPAP variables
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Biologic variable = the person (race, etc.)
PRE analytic variable = lifestyle (diet, etc.) Analytic variable = physical test (bad lab tech or equipment) POST analytic variable = results & diagnosis (transcribe & interpret) |
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Sensitivity means
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TRUE rate
* the ability to detect the truth (a disease when the disease is actually there) |
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rate of true positives in a population
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sensitivity
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False negative
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the test missed the disease when it was ACTUALLY THERE
(sensitivity problem = worst result is a false negative) |
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Specificity
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The results are negative in a patient that does not have the disease.
Don't know if this is trustworthy method. |
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False positive
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The patient doesn't have the disease, but the TEST SAYS THEY DO.
Specificity problem |
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Most COMMON test to eval. CIRCULATING BLOOD CELLS
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CBC
(C.irculating B.lood C.ells) |
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In a CBC (circulating blood cell test), automated instruments perform ___________ of the RBCs, WBCs and _________.
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quantization
platelets |
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2 main RBC measurements found in a CBC are __________ & __________
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Hemoglobin & Hematocrit
H & H |
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Blood to be run through CBC test is collected in a ____________-capped tube, inverted 4-5x and properly labeled with 4 pieces of info. Why this tube?
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LAVENDER
*because lavender cap tube has ANTI-coagulant |
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Hematocrit
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the % of blood volume occupied by RBC's [per unit blood]
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MCV
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Mean Corpuscular Volume = SIZE of RBC in a blood schmear
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schmear
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blood smear with NY accent
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NORMOcytic
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normal sized RBC
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MICROcytic
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small sized RBC
*usually due to LOW hemoglobin production |
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MACROcytic
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LARGE sized RBC
*usually means defect in maturation of RBC |
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MCH
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Mean Corpuscular HEMOGLOBIN = WEIGHT
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Average concentration of Hgb in average RBC
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MCHC
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Norm-o-chromic
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boring
normal in color RBC's so MCH (weight of hemoglobin) normal |
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Hypochromic
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pale, wilting violet RBCs.
Appear lighter in color w/ an increased area of CENTRAL PALLOR (uh, especially pale doughnut hole) *MCH (weight of hemoglobin missing so...) low |
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HYPERchromic
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crazy red RBC - no doughnut hole. Totally filled in with red. Red plate. Hyperchromic RBC is RED.
*MCH (weight of hemoglobin) above normal |
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RDW
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Red-cell Distribution Width
*UNIFORMITY of size and shape - there are NO units. CHANGE means UP. |
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What 2 vitamin deficiencies cause MACROCYTIC anemia?
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B9 & B12
(folate and cyancobalamin) |
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How to confirm CBC w/ differential?
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Peripheral smear
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Tests to detect Iron DEFICIENCY & SEVERITY
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IRON
FERRITIN TIBC |
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Fe down
TIBC up Ferritin down ESR, Ca, K = normal |
Not much iron bound (too many empty chairs, as per TIBC)
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With this descriptor, CHANGE means UP. It has no units.
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Red cell Distribution WIDTH (Uniformity of shape/size)
[+] RDW means a Change has occurred. This parameter is EITHER the same or changed to positive, never negative because that would mean 'reverting back to a former condition/time travel.' |
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Poikilocytosis
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Variations in the SHAPE of a red blood cell as viewed in a peripheral smear/microscope
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Different shapes of red blood cells in poikilocytosis
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Ovalocytes
Elliptocytes Sphereocytes Target cells Sickle cells |
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The cellular formation, proliferation, differentiation and finally maturation of blood cells
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Hematopoiesis
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Organs of hematopoiesis
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Spleen, lymph nodes, thymus, bone marrow, liver, RES
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Anisocytosis
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variations in the size of RBC's due to PATHOLOGY
*reflected in the MCV |
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difference between poikilocytosis and anisocytosis?
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poikilocytosis is size under a microscope/peripheral smear
anisocytosis is size due to pathology reflected in MCV |
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Normally, only ________ RBC's are released into the blood.
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MATURE
*when reticulocytes (immature RBC) are high in #, there is a problem |
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Process by which early erythroid precursor cells differentiate to become mature RBC's
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ERYTHROPOIESIS
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Erythropoiesis is regulated by _______. Why would this hormone be released?
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erythropoietin (kidney - EPO)
*released when body hypoxic [high altitude] |
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RBC maturation depends on _________ & _________ for DNA synthesis, maturation of nucleus and finally, division.
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B12 & Folate
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RETICULOCYTES
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slightly larger than mature RBC
the immature form of an RBC Increased EPO >> means increased RBC production and more retuclocytes ***MOST RELIABLE measure of RBC production |
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immature red blood cells, typically composing about 1% of the red cells in the human body. Develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells.
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RETICULOCYTES Like mature red blood cells, reticulocytes do not have a cell nucleus. They are called reticulocytes because of a reticular (mesh-like) network of ribosomal RNA that becomes visible under a microscope with certain stains such as new methylene blue.
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What is the connection b/w MARROW response and RETICULOCYTES?
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Marrow will force immature cells into circulation due to ANEMIA.
Reticulocyte count should be high if sys responding correctly to anemia. If reticulocyte normal DESPITE anemia, then marrow is NOT responding OR anemia is in EARLY stage. |
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Describe a MATURE erythrocyte
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FLEXIBLE & DE-FORMABLE for passage through microcirculation
Must have a normal intact MEMBRANE for survival/function |
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Oxygen-carrying protein in RBC's
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Hemoglobin
*low levels mean anemia |
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SYMPTOMS (subjective) of IRON DEFICIENCY anemia [12]
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Shortness of breath / Weakness / Fatigue / Faintness / Lethargy / Headaches / Pica (extreme) / Sore tongue / Palpitations / Paresthesias / Concave or spoon shaped nails / Chronic gastritis
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SIGNS (objective) of iron deficiency anemia [8]
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Pallor (skin and conjunctiva)
Cardiac fcn abnormalities Jaundice (hemolytic anemia) Fingernail deformities Tongue signs Tachycardia Neurologic findings |
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Severe anemia could give chest __________, _________ or ____________
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pain, angina or heart attack
*severe reduction of oxygen capacity can cause hypoxia and cause infarction w/o atherosclerosis relationship |
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Having both _________ & __________ doubles your chances of a heart attack.
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atherosclerosis & anemia
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Generally describe pernicious anemia presentation
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Thin to anorexic patient with unexplained wight loss has glossitis, constipation OR several BM's daily and feels heart is 'fluttering.' Patient has flatulence and bloated feeling. Has trouble breathing (dyspnea, tachypnea d/t congestive heart fail in severe case) and suffers from paresthesia/weakness/clumsiness or unsteadiness.
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Pernicious anemia presentation clinical:
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Weight loss of 10-15 lbs in 50%
Anorexia Glossitis, beefy tongue, burning sore tongue 50% Constipation or constant bm's Nausea, vomiting, pyrosis, farting and fullness Urinary retention, impaired micturition d/t SC damage UTI's Paresthesias - glove n stocking, common in patients taking folic acid/folate Tachycardia, flow murmurs Dyspnea, tachypnea + CHF in severe pernicious anemia |
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Presentation of IRON deficiency anemia patient
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PICA (extreme)
Sore tongue Concave or spoon shaped nails Chronic gastritis |
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Sickle cell anemia patient presentation
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Abdominal pain
Bone pain most common in sickle cell crisis due to INFARCTS |
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Symptoms of LEAD poisoning
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Abdominal pain
Brain sx in children Peripheral nerve or cord sx in adults |
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What two anemias cause abdominal pain?
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Lead poisoning and sickle cell anemia
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Signs of lead poisoning
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X-ray
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Likely lab results of anemia:
1. Is there anemia? 2. What morphology (type)? 3. Cause of anemia? |
1. H & H low
2. MCV, MCH, RDW 3. Blood tests specific to certain anemias; CBC gives guidance to find cause |
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Describe CHRONIC blood loss anemia
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Blood loss in small amounts over time
MOST COMMON from GIT First normochromic + normocytic, then gruadually microcytic + hypochromic as Iron stores depleted |
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MOST common CAUSE of anemia
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IRON DEFICIENCY!!
*Normochromic, normocytic becomes hypochromic, microcytic (small and pale) **Decreased MCV & MCH but increased RDW d/t changes in size and shape {poikilocytosis + anisocytosis = elliptocytes} |
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What is the cardinal sign of megaloblastic anemia?
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Pancytopenia due to B12 or Folic acid deficiency
Megaloblasts are RBC precursors in MARROW (vs. blood which would be microcytic) |
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What do I mean by Megaloblastic RBC precursors in the MARROW?
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Megaloblastic refers to RBC precursors in the marrow that has an odd SEIVE-LIKE appearance of the NUCLEAR CHROMATIN
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Megaloblastic cells usually appear __________
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MACROcytic (big = mega!)
*major ABNORMALITY is the diminished capacity to synthesize DNA but RNA synth less affected so cells just grow and grow cytoplasm until MEGAsized! |
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Describe the cells of MEGAloblastic anemia
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MACROCYTIC
Enlargement of rapidly proliferating cells = PANCYTOPENIA MARROW - sieve like nuclear chromatin Unchecked cell growth - CAN'T synthesize DNA RNA less impeded so cytoplasm grows and grows, ENLARGES CELLS ****B12 or FOLIC ACID DEFICIENCY almost always**** |
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stab cells
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analagous to reticulocytes on a CBC
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Describe sickle cell anemia
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Substitution of VALINE for GLUTAMIC ACID on the B chain transforms
Hgb A into Hgb S** RBCs more prone to trauma due to rigidity Decreased OXYGEN TENSION causes Hgb cells to CRYSTALIZE and PRECIPITATE out, CAUSING SICKLING (shape) of the cell |
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Along with SEVERE pain, ________ & _______ may occur in sickle cell anemia.
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Hemolysis & Vaso-occulusion
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Condition which may cause severe pain, hemolysis and vaso-occlusion; ISCHEMIA and INFARCTION to vital organs.
Which organs? What disease? |
Sickle cell anemia
Kidney, spleen, brain [plugged capillaries ->>INFARCT] |
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THALASSEMIAs
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a group of inherited MICROCYTIC anemias characterized by defective Hgb synthesis...
usually deletion of genes controlling the alpha or beta globulin chain |
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Cancers usually result in ___-cytic cells
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MACRO
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Regarding thalassemias, the globulin chains controlled by defective Hgb synthesis which deletes genes controlling alpha/beta globulins are formed BUT?
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the RATE of sythesis is decreased.
[usually mild; exertion can give fatigue] |
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Target cells are called
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CODOcytes
*Hemoglobin-C dz |
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Target cells (codocytes) are often seen in ?
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HEMOGLOBIN - C disease
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3 types of Thalassemias
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BETA
MAJOR [COOLEY'S] MINOR |
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BETA Thalassemia
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B-chain production DECREASED, structural genes present but mRNA not produced efficiently nor degraded fast enough.
***MOST COMMON thalassemia - seen in MEDITERRANEAN peeps [mid eastern, too] |
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Thalassemia MAJOR= no hemoglobin A
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COOLEY'S deadly- ANISOCYTOSIS (size), POIKILOCYTOSIS (shape), HEINZ BODIES (blue stained knob)
HOMOzygous; anemia is severe w/ JAUNDICE, FAILURE TO THRIVE, and survival DEPENDENT ON TRANSFUSION |
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Thalassemia MInOR
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Heterozygous and usually ASYMPTOMATIC
Mild MICROCYTIC anemia NORM >>DEcreased Hgb w/ RBC's normal to ELEVATED |
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Heinz body is one of many types of ______________________
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INCLUSION BODIES
*precipitates |
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test for abnormal hemoglobin
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ELECTROPHORESIS
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Thalassemia Major Hbg problem?
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no Hgb A (adults)
all Hgb F (embryonic) |
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The RBC actively uses ATP to maintain the ________of the cell membrane.
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FLEXIBILITY
*in Hemolytic anemia, we are missing enzymes that make ATP, so we cannot keep membranes flexible |
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G6PdH deficiency
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hemolytic anemia
Usually asymptomatic and normal CBC except when hemolysis induced. HEINZ bodies show up (infection, fava beans) 'favism' JAUNDICE appearance DUE TO BILIRUBIN released from lysed RBC |
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PYRUVATE KINASE deficiency
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Hemolytic anemia
Exacerbated by acute illness, viral infection, pregnancy TYPICAL hemolytic lab presentation |
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a group of disorders whose common feature is the presence of ANTIBODIES to antigens on RBC
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AUTOIMMUNE HEMOLYTIC anemia
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WARM autoimmune hemolytic anemia
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Autoantibodies bind to RBC;s optimally at 37 deg. cel.
Antibodies are most often IgG SLE and other immune disorders/ CLL, malignancies |
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COLD autoimmunie hemolytic anemia
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Autoantibodies bind to RBC w/ greater affinity at less than 37 deg.
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TEst used to detect DRUG INDUCED hemolytic anemia
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DIRECT & INDIRECT COOMB'S TEST
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Cell has BASOPHILIC STIPPLED appearance
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blue polka dots = LEAD POISONOING
*anemia due to toxic hemolysis |
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too many RBC's
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POLYCYTHEMIA
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Myeloproliferative disorder that behaves almost like a cancer/neoplasm...marrow pumping out ALL THREE CELL LINES
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POLYCYTHEMIA VERA [PRIMARY]:
myeloproliferative absolute increase in all cell types (RBCs, WBCs, and platelets) Occurs later in life (40-60 yo) 3 major criteria: splenomegaly, normal O2 saturation, Increased red cell MASS |
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Low EPO levels, bone marrow hypERcellular
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Polycythemia VERA [primary]
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Is polycythemia vera chronic, acute? Patient presentation?
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CHRONIC
CARDIAC & THROMBOSIS complications Myelofibrosis may develop + leukemia [viscous blood w/o transfusions - heart works too hard b/c has to pump too hard] |
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ABSOLUTE polycythemia
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SECONDARY
due to HYPOXIA Mediated by EPO - ie, mountain climbing response Elevated RBC's, Hemoglobing, Hematocrit, BUT... WBC's and PLATELETS are NORMAL |
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Most common RBC disorder
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ANEMIA
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definition of anemia
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reduction in RBC, hemoglobin concentration or hematocrit
reduction in H & H and RBC (ie, pathologic decrease like bleeding to death) |
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Humans need to be above ___________ platelets
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100,000
~avg is 150,000 |
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If platelet count below 50,000, then patient will
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bleed to death during surgery
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If platelet count below 20,000, then patient will
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spontaneously bleed
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The differential count is the total # of WBC that is broken down into 3 types (BEN). If elevated, then bad.
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PMN's
(Basophils, Eosinophils, Neutrophils = granulocytes!) |
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Broad descriptions of 3 types of anemias
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Leaking
Not making them Crushing/breaking them |
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Jaundice only applies to _________ anemia because of bilirubin.
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hemolytic
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When the patient begins to be anemic, the body may respond by increasing the number of ___________
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RETICULOCYTES
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Describe chronic blood loss anemia
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Normochromic & normocytic
then... Hypochromic and microcytic (Fe deficiency) |
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Test for chronic blood loss anemia
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OCCULT blood found via GUAIAC test
*commercially called the Hemoccult - tests for Hgb in stool. Blue poo means blood. |
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Where is iron stored?
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Liver
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Most common cause of anemia
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IRON deficency anemia
WHEN FULLY DEVELOPED, there is insufficient iron for normal Hgb production. MICROCYTIC, HYPOCHROMIC |
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5 mechanisms of iron deficiency
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1. DIET (all carbs, no protein)
2. insufficient Fe ABSORPTION 3. insufficient transport via TRANSFERRIN 4. abnormal LOSS of iron 5. increased iron REQUIREMENT [preg] |
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most common causes of Iron deficiency
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GI or vaginal bleeding in women
GI bleed in men |
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Treatment of IRON deficiency anemia
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Oral iron
Correction of MALabsorption Correction of BLEEDING |
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Iron deficiency could not only be from GI or vaginal bleeding but also from __________
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PARASITES!
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GOLD lab analysis:
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Hemoglobin
~transferrin and Beta-globulin regulates ~High transferrin levels mean body can fight infection ~Determine BOTH iron transferrin & TIBC levels to d/dx b/w anemias ~INCREASED= hemolytic dz, acute liver problems ~DECREASED= Fe+ deficiency anemia, chronic blood loss [GI] |
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Measuring Fe+ is measuring the amt of ________ iron to _________
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iron BOUND to TRANSFERRIN
*never measures free iron; too hard |
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Carrier protein of Fe+
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TRANSFERRIN
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The liver secretes _________, which combines with Fe+ to form _________, the iron transport protein.
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apotransferrin (liver)
TRANSFERRIN [iron tranny] |
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Lab results:
Is there anemia? |
H & H is down
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Lab results:
What morphology/form/type of anemia? |
MCV, MCH, RDW
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Lab results:
What is the cause of the anemia? |
Use specific blood tests. CBC guides you to find the cause.
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CF- IRON deficiency anemia
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parasthesia
chronic gastritis angular stomatitis pica koilonychia [club or spoon] |
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TIBC
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Total Iron Binding Capacity
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Iron level [serum] high, then TIBC level is ____
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low.
Usually. May still be normal b/c body using STORED iron. Takes awhile. *TIBC is total iron binding capacity so will be high because all empty seats in stadium [all the iron is out in the parking lot/blood serum] |
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Iron deficiency lab results
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low MCV ~ low MCH
high RDW due to size and shape changes such as anisocytosis and poikilocytosis - eliptocytes *RETICULOCYTES are usually normal in beginning of Fe+ def. Hypochromic, microcytic, RDW changes |
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TEST for the cause of iron deficiency anemia (2)
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1. SERUM IRON [sIron] decreased
2. TOTAL IRON BINDING CAPACITY [TIBC] increased *Serum iron measures Fe bound to transferrin, reflecting RATE of Fe+ delivery to tissues **TIBC measures amt of TRANSFERRIN. Number of Fe+ binding sites increases as iron decreases (empty seats) |
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Where is iron in the body? 3 places
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Bound to Ferratin
Hemoglobin Ionic (small, insignificant amt) |
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Why may TIBC still register 'normal' when underlying iron deficiency exists?
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Body is using stored iron
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Transferrin & pregnancy...
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increased during 1st trimester due to estrogens
iron increases with transferrin but then... transferrin decreases 3rd trimester back to normal HOWEVER iron use increases due to fetus parasite Woman can appear iron def. but not anemic, as her H&H remain w/in normal limits |
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a pregnant woman can give a false negative iron deficiency result because?
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based on normal H&H levels she appears okay but without a TIBC test to monitor transferrin, which has probably dropped if she's in 3rd tri, she is masking anemia
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Negative acute phase reactant protein
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TRANSFERRIN
*decreases in acute diseases, or severe chronic diseases. TIBC % of available binding sites for iron can appear low or low-normal but actually be OUTRIGHT DOWNRIGHT LOW! *Do not confuse the amount of tranferrin with the binding capacity |
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Tumors that like the posterior elements of the spine (ie, pedicles)?
*Yes, this is a bone and joint imaging question but you need to know it anyway |
ABC/GCT/OB/OCh/OO
'flavor burst tumor' of center lucent nidus <1cm surrounded by sclerosis, ie, osteoid osteoma OO |
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Equation which demonstrates how well the transferrin saturated [amt of USEFUL iron/bound to transferrin]
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TS: Transferrin Saturation
*% Transferrin = sIron / TIBC *This test determines ALTERED transferrin levels |
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MOST USEFUL TEST in the evaluation of Fe+ status in body
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sFerritin [Serum Ferritin]
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Used in conjunction with sIron and TIBC to give idea of true iron status
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sFerritin
[serum Ferritin] |
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sFerritin is sensitive and a decrease can be seen in early iron deficiency anemia before there is evidence of reduced _________.
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H&H
sFerritin is directly related to total body iron stores MOST USEFUL test for iron status = reveals 1st clinical change in iron, as in HOW MUCH of the STORE has been used? |
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TS
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Transferrin Saturation
Shows what % of iron is BOUND to transferrin |
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TIBC
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Total Iron Binding Capacity
Measures specific number of available iron binding sites on transferrin. This number INCREASES as the iron level decreases (empty seats available, measured by TIBC) |
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sIron
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serum Iron
reflects RATE of iron DELIVERY to tissues by measuring iron bound to transferrin. Drops w/ reduction in stores. |
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Coomb's test
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test to detect, directly or indirectly, DRUG-INDUCED HEMOLYSIS
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test to detect, directly or indirectly, DRUG-INDUCED HEMOLYSIS
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Coomb's test
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Main storage form of iron
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ferritin
(iron + apoferritin = ferritin) |
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Why would intestinal absorption of Fe+ change?
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The body is saturated with Fe+.
Fe+ joins apoferritin = FERRITIN Maximum saturation of ferritin causes rate of Fe+ absorption at intestine level to DROP |
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Test for patient with restless leg syndrome
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sFerritin [serum ferritin for anemia]
*The MOST COMMONLY associated med condition of RLS is iron deficiency ~ 20% of all cases |
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Macrocytosis means
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large RBCs.
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Megaloblastic refers to
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RBC PRE-cursors in the MARROW that have an odd, sieve-like appearance of the nuclear chromatin.
*remember that megaloblastic anemic cells have diminished DNA ability - the sieve appearance will be the detail you need on the test. Megaloblastic is often confused w/ macrocytic anemia. Megaloblastic are macrocytic SIZE, but macrocytic anemia takes place in the blood while mega is in the marrow. |
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*remember that megaloblastic anemic cells have diminished DNA ability - the sieve appearance will be the detail you need on the test. Megaloblastic is often confused w/ macrocytic anemia. Megaloblastic are macrocytic in SIZE {MacroCYTOSIS}, but macrocytic anemia takes place in the _______while mega is in the ________.
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macrocytic = blood
megaloblastic = marrow where cells are in macrocytosis state of enlargement |
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Most common causes of MACROcytic ANEMIA
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*NOT macrocytosis - that's megaloblastic anemia in the marrow
Most common causes of Macrocytic anemia = B12 & Folate deficiency |
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Besides B12 and Folate deficiency, other common causes of MACROCYTIC anemia?
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DRUGS
CHRONIC LIVER DZ Hypothyroid Multiple Myeloma Myeloproliferative dz [leukemia/mylofibrosis] |
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Name the common causes of enlarged RBC's in the blood
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MACROCYTIC anemia:
B12 and folate deficiency (MC) Hypothyroid Multiple myeloma Myeloproliferative dz like leukemia or myelofibrosis Drugs Chronic Liver dz |
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Specific KINDS of macrocytic anemias
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FOLATE
FACTOR DEFICIENCY - B12 {pernicious anemia} *think megaloblastic madness! |
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Describe Folate deficiency anemia
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>Megaloblastic in blood b/c macrocytic
>Impaired DNA synth in RBC precursors b/c megaloblastic seive-like chromatin >Hypersegmented neutrophils >Large platelets >all cells are affected = PANCYTOPENIA |
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Describe the neutrophils of Folate deficiency anemia
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HYPERsegmented (recognize on slide)
White cell granulocyte neutrophil w/ normally segmented nucleii that has become HYPERsegmented! |
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Mechanisms of FOLATE deficiency (who gets it?)
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NON-eater ALCOHOLICS
PREGO using excess folate CRAP CELLS = decreased reticulocytes so healthy cells not being made SERUM FOLATE decreased because ABSORPTION decreased INHIBITED folate synthesis RBC folate decreased - storage folate...there is a certain amt of folate stored in RBCs; this is an accurate measure of folate in body DIALYSIS patients |
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LAB results of FOLATE deficiency
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MACROCYTIC anemia:
MCV elevated (ie, "macro" means size/Volume increase) Hypersegmented neutrophils on slide + MacroOVALOcytes Reticulocytes down (old crap cells only- no healthy cells being produced) Serum folate reduced RBC folate reduced (stores depleted) |
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If person has not suddenly increased or decreased folate [ie, pregnancy], then what is best measure of folate status?
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SERUM folate
*if intake has changed, then RBC stored folate level [erythrocyte folate] is better reflection of stored folate |
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Folate deficiency is one kind of macrocytic anemia. What is the other kind?
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FACTOR deficiency - B12 pernicious anemia
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Regarding B12 factor deficiency anemia, what should be investigated regardless of clinical anemia development?
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MCV - if your RBC's have increased in size, then they need investigation.
MCV may increase long before actual anemia shows up. |
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Tests for Factor B12 deficiency
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1. Serum B12 assay
2. Marrow examination 3. Schilling test for malabsorption |
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Serum B12 is tested and marrow is tested for factor B12 deficiency anemia. Why marrow?
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B12 is necessary for all 3 cell types (platelets, WBC's and RBC's)
If all are affected, then B12 is the culprit |
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Serum B12, Marrow exam for 3 cell type affects, and ____________ test for __________ are the tests for macrocytic Factor B12 deficiency.
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SCHILLING test for B12 malabsorption.
Will tell you if there is malabsorption and why. |
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Schilling test depends on first part without __________, then second part adding ___________.
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part I - NO Intrinsic Factor
part II - add Intrinsic Factor *IF is a glycoprotein made by parietal cells in stomach. Vitamin B12 binds w/ proteins in gastric juice, then dissociates from them in terminal ileum. There it binds w/ IF to enter portal/liver circulation. |
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Describe Schilling test part I
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Part I [no IF's, and's or but's]:
Tagged oral B12 swallowed. Injection of nonisotopic (non radioactive/non tagged) B12 next, saturating binding sites. If tagged B12 was absorbed in gut, then it's secreted in urine. Measure radioactivity of urine tagged B12. NORMAL = minimum amt. of tagged B12 appears in urine ABnormal = person w/ malabsorption will have LESS THAN minimum amt in urine, meaning tagged B12 was NOT absorbed in the gut due to several things, including lack of Intrinsic Factor. *end of part I Schilling test for malabsorption B12 |
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Why injection of nonisiotopic B12 in Schilling part I?
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The injection saturates the tissue B12 binding sites and causes some portion of the oral TAGGED B12 to be flushed into the urine if it was originally absorbed in the gut. This would be a normal finding - some minimal amt of radioactive tagged B12 in the urine if person does not have a malabsorption problem. If patient has no tagged in urine, then malabsorption problem so little to none is found in urine. If this happens, then Schilling part II!
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Schilling part II for B12 malabsorption
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Person's urine had little or none radioactive tagged B12 in urine during part I...
Repeat test but add INTRINSIC FACTOR to TAGGED radioactive ORAL B12. If from pernicous/B12 anemia, then tagged B12 should be normal portion in urine because the addition of IF made absorption suddenly possible in the gut. (Remember B12 binds w/ IF in terminal ileum, if it was absorbed to begin with, and binds to IF so can enter portal circulation). If pernicous/B12 anemia is not cause of problem, then investigate further. |
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In Schilling test part II, if the patient does not have pernicious anemia, what was the test end result?
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The addition of IF in part II made no difference (still no tagged B12 in urine), so other tests must be done.
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Normo-normo lab results?
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Anemia of chronic dz
Hemolytic dz We don't know... Look at platelet count at 136k = sorta low ALL 3 cell lines affected = look at DIFFERENTIAL to see some sort of neoplastic process going on *SOMETHING WRONG WITH THE MARROW is a good guess, vs. factor B12/iron/folate. Only one that would affect all three cell lines is B12. Macrocytosis but the MCV is not elevated (meaning size is okay so not factor def) |
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Differential count tells us
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how many WHITE cells (BEN) of each
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Cells start as undifferentiated stem and specialize. Just like the reticulocyte is the teen step before the RBC, the BAND cell is also called a STAB cell. The band cell is an intermediate _________
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granulocyte
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Immature granulocytes are called?
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Stab/Band cells
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In blood, all have mature reticulocytes but nothing less mature than a ________ cells.
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Band/Stab
*no metamyelocyte, myelocyte, promyelocte, myeloblasts are NOT present |
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A large ______ cell count or any of its precursors (myelocyte, metamyelocyte, etc.,) it is called a SHIFT TO THE LEFT.
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band
or even one precursor means a SHIFT TO THE LEFT |
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SHIFT TO THE LEFT is so named because
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we read left to right.
Cell development is always mapped from left to right. Anything immature is reading left. Mature is reading right. |
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If BAND cells are significantly increased, then 2:
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1. INFECTION
2. NEOPLASM |
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If precursors are present in peripheral blood, then 1
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NEOPLASM only
*most likely some sort of leukemia |
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You can see BAND cells w/in the blood in a certain range but when you see excess or ______________, you got a problem!
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precursors to band/stab cells
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Segs
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Segmented cells:
NEUTROPHILS/POLYMORPHONUCLEOCYTE/GRANULOCYTE = segs |
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Where do Segs live?
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Marrow
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Function of neutrophils
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Spread out to tissues
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Once PMNs leave circulation, they never
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return. They are out on patrol forever.
*****Know this***** |
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What stimulates eosinophils?
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Allergies and parasites
(and septicemia, according to Morrocan study) |
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Basophils function in __________ reactions
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hypersensitivity
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Monocytes
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precursors to tissue macrophages that are tissue scavengers (hunter/killers that break up debris)
This is why there are few in circulation because they don't hang out in blood circulation - they are in the tissues hunting |
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Tissue macrophages
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can proliferate, tag, kill, hunt within the tissues
*APC = Antigen Presenting Cell to T-lymphocytes |
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Lymphocytes
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B cells [bone maturation]
T cells (thymus maturation) *go to lymph tissues. CAN GO BACK AND FORTH BETWEEN TISSUES AND BLOOD. They are the only ones that have gills and lungs. |
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Helper cells vs. Killer cells
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Both T cells
CD4 helper CD8 killer [cytotoxic/suppressive] |
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leukocytosis vs. leukopenia
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WBC up, WBC down
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Differential count
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The # of each cell type is expressed as a % of the total number of cells counted.
100 is our base. |
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Absolute Concentration
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when evaluating a sample for a differential count, only absolute concentrations should be used:
AC - Total WBC x % of cell type = the # of that particular cell type |
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On page 10 of lab results, notice differential is listed as how many NLMEB's. Absolute concentrations are listed. How do I know if one of my NLMEB's is out of whack or is an artifact of counting?
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(WBC #) 6.0 x .445 (Neutrophils @ 44.5%) = 2.7 absolute neutrophils
IF the absolute concentration is WITHIN normal limits, there is NO abnormality. |
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When you look at WBC count down, you don't know which is down until you look at the _____________
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differential
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FELTY'S syndrome
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rare form of rheumatoid arthritis
*granulomatous disease. White cell count get so depressed it's like having AIDS. |
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Neutropenia
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a DECREASE in the number of ABSOLUTE circulating neutrophils
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Neutrophilia
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an increase in the ABSOLUTE # of circulating neutrophils = acute bacterial infection
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LEUKEMOID REACTION
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WBC ct greater than 50k/mm3 so wayyyyyy up. A differential WBC count of GREATER THAN 5%
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What is the LIMIT of stab cells?
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5%
If there are ANY precursors, then shift to the left. IF stab over 5%, then shift to left. |
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***Absolute increase in lymphocytes, is an ______________differential.
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inverted
more lymphocytes than PMNs/neutrophils****VIRAL infection |
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Classic example of ATYPICAL LYMPHOCYTE
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mononucleosis
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Leukemia (part II boards) Basic 2 types w/ subtypes and description
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Malignancy of MARROW
ACUTE & CHRONIC |
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Which cells are haywire in leukemia?
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MYELOGENOUS leukemia is wonky BEN cells (granulocytes)
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Lymphocytic leukemia involves
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lymphocytes!
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ACUTE leukemia types
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1. Acute Lymphoblastic
2. Acute MYELOblastic *cells in acute leukemia are blastic |
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In acute leukemia, the marrow is cranking out the earliest of immature forms....____________
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myeloblasts (wayyyy left -earliest precursor)
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Important diagnostic criterion for acute LYMPHOblastic leukemia
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% of blasts found in the bone marrow is 30% or more
*BONE PAIN is signal! |
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Where is bone pain w/ acute lymphoblastic leukemia?
What are growing pains like? |
LONG bone pain
d/dx for exclusion of GROWING PAINS: Typically pre-pubescent or adolescent. Typically bilateral lower extremity, night time, easily relieved by aspirin or acetominaphen, asymptomatic during day. No fever, no weird vitals. |
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ALL
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Acute Lymphoblastic Leukemia (ALL)
Proliferation of lymphocytes Peak in 2-10, then older to middle age adults *Marrow and Smear [AUER rods] |
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Inclusion bodies of ALL
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Auer rods of ALL
*clear streak through a blastic cell suggests myelogenous vs. lymphoblastic leukemia |
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How to test ALL
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marrow and smear, look for Auer rods
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CHRONIC LEUKEMIA
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2 types:
Chronic Myelocytic/Myelogenous Leukemia (CML) adults Chronic Lymphocytic Leukemia (CLL) |
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CML lab
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WBC skyrockets in PERIPHERAL BLOOD, rather than marrow
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CLL
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mature but not normal mature cells that go into cells and cannot make Plasma cells, ergo cannot make ANTIBODIES so susceptible to every damn thing
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CLL die of infections because
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they can't make plasma cells so can't make antibodies
*indolent dz/ lazy dz because it's slow kill |
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CLL has ________ cells, whereas ALL has Auer rods.
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SMUDGE cells
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_____might increase long before anemia appears
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MCV
*just like ferritin with iron deficiency anemia |
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reveals all three cell types are affected
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Bone marrow exam
WBC, platelets and RBC = PANCYTOPENIA |
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test to detect B12 malabsorption
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Schilling test {after serum B12 test}
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If the INTRINSIC FACTOR makes no difference in the patient's urine, then
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the patient does not have pernicious anemia and there is another reason for the malabsorption
i.e. small bowel...Crohn's dz, celiac sprue (Schilling part II) |
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ATROPHIC GASTRITIS
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multiple cells in stomach atrophy due to age (G-cells, parietal cells that make IF) therefore we get decreased to none level of IF and...
***develop B12/pernicous anemia due to no IF Anyone can develop atrophic gastritis |
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Intrinsic factor is a ___________ made by _________cells in the stomach. It is required for _____ absorption.
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IF:
glycoprotein parietal cells in stomach B12 absorption B12 binds with proteins in gastric juice, dissociates from them in terminal ilieum and binds with B12 instead to enter the PORTAL circulation. |
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Term used to cover any number of different types of B12 malabsorption syndromes, including but not limited to lack of or dysfunction of INTRINSIC FACTOR.
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PERNICIOUS ANEMIA [B12]
*pernicious and B12 deficient are not necessarily synonyms but are used as such in the literature |
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Causes of PERNICIOUS anemia
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Inadequate dietary intake (vegetarians)
Atrophic gastritis (aging cells stop making IF in stomach) Gastroectomy Ingestion of caustic substances (burn) Functionally ABNORMAL IF |
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Pernicous anemia/B12 causes:
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ANTIBODIES to IF
[autoimmunity] Inadequate PROTEOLYSIS of dietary B12/cobalamin Insufficient PANCREATIC PROTEASE [pancreatitis, Zollinger-Ellison syndrome] BACTERIAL OVERGROWTH intestine [blind loop syn, diverticulitis] Disorders of ILEAL MUCOSA [resection, ileitis, Crohn's, sprue, lymphoma, amyloidosis, absent IF receptor, ~Imerslund-Grasbeck syn~, drugs] |
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The adult form of pernicous anemia is most common in what ethnicities?
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Celtic {English, Scottish, Irish}
& Scandinavians |
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B12 deficiency anemia occurs more frequently in _______ of English, Scandinavian or African descent.
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females
but there is an EQUAL GENDER DISTRIBUTION IN THE U.S. [can occur in all ethnic groups] |
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CLASSIC B12 deficiency TRIAD:
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WEAKNESS
SORE TONGUE PARESTHESIA |
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Usually medical attention is sought for something else and B12 deficiency anemia is discovered when ____ is high.
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MCV
[classic triad of weakness, sore tongue and paresthesias are not usually chief complaint] |
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General findings of B12 anemia
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Weight loss of 10-15 lbs in 50% of patients
Anorexia - most patients Low grade fever - 1/3 of patients |
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B12 anemia is often well tolerated despite patients having ____________levels in the mid-teens.
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hemocrit
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Describe heart of B12 deficiency anemic
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Cardiac output [CO] INCREASED in hematocrits less than 20%
Heart rate is ACCELERATED/ TACHYCARDIA CHF and CORONARY INSUFFICIENCY usually only occur if pre-existing heart dz |
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GI findings of B12 deficiency anemic
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SMOOTH TONGUE = glossitis w/ loss o papillae along edges of tongue
Painful, SORE TONGUE = beefy red patches on dorsum of tongue BURNING/SORENESS mouth or tongue CHANGES IN TASTE, LOSS OF APPETITE [anorexia] CONSTIPATION = semisolid bowel movements daily NAUSEA, VOMITING, PYROSIS [heartburn], FLATULENCE, SENSE OF FULLNESS Abdominal pain of rigidity |
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Pyrosis
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heartburn assoc. w/ B12 deficiency
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Genitourinary sys findings of B12 deficiency anemic
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Urinary RETENTION = impaired micturition (can't pee) - may be SC damage predisposing patient to UTI's
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Nervous system findings of B12 deficiency anemia
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PARESTHESIA [numbness, tingling]
WEAKNESS CLUMSINESS UNSTEADY GAIT |
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Of all the megaloblastic disorders, only ______________ causes neurological deficits.
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B12 deficiency anemia
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Why does clumsiness & unsteady gait of B12 deficiency become worse in a dark room?
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proprioreception affected = LOSS due to myelin degeneration of dorsal columns and cerebral cortex. B12 def. anemia is a combined systems disease!
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Neurological sx and findings may be absent even in the presence of B12 def. anemia. Why?
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Masked by folate intake.
*pt taking lots of folate can get under the radar |
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Type of paresthesias in B12 def. anemia?
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glove and stocking (like Guillan-Barre )
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Older patients w/ B12 def. anemia may present with sx of ?
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dementia/Alzheimer's, personality changes, memory loss, irritability
'megaloblastic madness' |
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APPEARANCE of person w/ B12 def. anemia
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LEMON-YELLOW, WAXY PALLOR
PREMATURELY WHITENED HAIR |
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CARDIOVASCULAR B12 def. anemia sx
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TACHYCARDIA w/ flow MURMURS
dyspnea, tachypnea & evidence of heart failure |
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Mental state and vision/hearing of B12 def. anemia
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Abnormal mental state, w/ loss of vision/hearing such as RETINAL hemorrhages and exudates
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Organs of B12 def. anemia
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Liver = HEPATOMEGALY
Spleen = SPLENOMEGALY - can feel tip of spleen |
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Remember, only one anemia causes nervous sys. changes
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B12 anemia
So with recent loss of mental capacities, somnolence, dementia, pyschosis, depression = suspect B12! |
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Combined systems disease
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Glove and stocking paresthesia
Difficultly w/ gait, balance Loss of position sense in second toe Loss of vibration detection for 256Hz, but not 128 Hz fork = can lead to SPASTIC ATAXIA from cord demyelinization if left untreated |
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Earliest signs of posterolateral columns disease
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Loss of position sense in 2nd toe and inability to detect vibration of 256 Hz fork, but no 128 Hz fork.
*demyelination of dorsal and lateral columns due to B12 deficiency anemia can lead to spastic ataxia if untreated. |
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Two causes of megaloblastic anemia which must be differentiated?
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Folate & B12 deficiency
Folate masking B12 deficiency is d/dx for megaloblastic anemias |
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The therapeutic use of folate can mask B12 deficiency because
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If pharma folate taken, it skips the B12 step where B12 is involved in making folate de novo.
We won't know the status of our B12 if folate is delivered to the body from outside. |
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The chemicals B12 acts on to make folate are involved in the production of?
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DNA and RNA
The folate dose allows the RNA development to continue (hence megaloblastic) and corrects the morphology of the cell in B12 anemia, but there simply isn't enough B12 to properly function. Neurologic damage occurs. |
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CHRONIC DISEASES that have associated anemias:
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Chronic infections
Rheumatoid arthritis Autoimmune disorders {SLE} Malignancies |
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Patients w/ pernicious anemia have, in addition to lemon-yellow waxy pallor and premature whitening of hair, a frame that is ?
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flabby, bulky and generally incongruent w/ severe anemia and weakness
(white people) |
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APLASTIC anemia
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PANCYTOPENIA [decrease in all three cell types = WBC, RBC, platelets]
*associated w/ HYPOcellularity of bone MARROW. Fewer colony-forming units, decreased pluripotent stem cells. Once this craps out, may not self-correct |
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Anemia of CHRONIC disease is a RBC _____________ disorder, meaning not enough red blood cells are produced, due to a resistance to _____________ and defects in mobilization of Fe from macrophages to _________, resulting in sequestration of the Fe in macrophages.
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HYPOPROLIFERATIVE RBC
ERYTHROPOIETIN resistance TRANSFERRIN |
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Anemia of chronic illness is usually mild and overshadowed by some godawful disease. The appearance of cells is __________ & __________
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Normochromic & Normocytic [may be microcytic]
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Iron sequestering in macrophages
Hypoproliferative RBCs due to EPO resistance |
Chronic illness anemias also have low serum iron [sIron], low/normal TIBC, lower SATURATION of iron
but... NORMAL FERRITIN (storage iron) |
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Low serum iron
Low/normal TIBC Low % saturation of iron Low H & H |
CHRONIC:
Reticuloctyes NORMAL Ferritin NORMAL MCH, MCV, MCHC NORMAL |
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Cause of anemia of RENAL INSUFFICIENCY
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defective EPO production
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Because free Fe+ is toxic and microbes love iron, as well as iron promoting malignant cell growth, the theory of tx for anemia of chronic disease?
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Leave it alone. It might be adaptive.
Higher mortality rate in patients treated w/ erythropoietin. |
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Nomorchromic Normocytic Anemia with INCREASED reticuloctyes
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Normo-normo, RETICULOCYTE INCREASED
Early hemolytic disease Acute blood loss Chronic blood loss - ie, alcoholism, GI problems. Test w/ guaiac screen. |
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Normochromic Normocytic anemia with NORMAL reticuloctyes
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Malignancy
Myeloma Chronic dz Refractory anemia |
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Aplastic anemia is defined as __________. It is associated w/ hypOcellularity of ____________.
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PANCYTOPENIA
hypOcellularity of bone MARROW = APLASTIC ANEMIA |
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Normochromic normocytic anemia w/ NORMAL reticuloctyes is due to malignancy, myeloma, chronic dz, or refractory anemia. LAB?
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DECREASED H&H
Unchanged WINTROBE indices |
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How does APLASTIC pancytopenia compare to B12 pancytopenia?
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same
Both affect all 3 cell types [WBC, RBC, Platelet] and w/ B12 you aren't making enough cells so hypocellularity of bone marrow. Results in disruption of all 3 cell lines. |
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APLASTIC anemia may be acute and fulminating, leading to death or it may be
|
insidious and chronic.
Aplastic anemia may be acute or chronic. 50% of case due to BONE MARROW DAMAGE FROM RADIATION, DRUGS/CHEMICALS [Benzene]. 50% are idiopathic! |
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Lab findings for Aplastic anemia
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Decreased RETICULOCYTES and ALL 3 CELL LINES due to PANCYTOPENIA
HYPOCELLULAR BONE MARROW in biopsy |
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HEMOLYTIC anemia RETICULOCYTES
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INCREASED!
*body says to make more RBC's because they are being lysed |
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HEMOLYTIC anemia patient will have JAUNDICE because
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RBC's are breaking down, bilirubin leaks out
DIRECT & INDIRECT bilirubin so patient has JAUNDICE |
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HEMOLYTIC anemia patient will demonstrate the presence of _______ at 3-5x normal range
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LDH
*Lactate DeHydrogenase |
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HEMOLYTIC anemia patient:
serum __________ DECREASES urine __________ INCREASES serum ______ MAY increase |
serum HAPTOGLOBIN decreases
while... urine UROBILINOGEN increases and serum IRON MAY increase |
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HAP is up
URO is down IRON may increase |
HEMOLYTIC anemia
*do a hemoglobin electrophoresis & guaiac test for occult blood in stool |
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Rh factor anemia
|
a form of hemolytic anemia
(Rh isoimmunization is a genetic mismatch) |
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Haptoglobin test
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Haptoglobin testing is used primarily to help detect and evaluate hemolytic anemia and to distinguish it from anemia due to other causes; however, it cannot be used to diagnose the cause of the hemolysis.
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When is haptoglobin test ordered?
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The haptoglobin test is ordered when you have symptoms and signs of anemia, such as paleness and weakness, along with findings suggestive of hemolytic anemia, such as jaundice and dark urine.
*The doctor may also order the test in conjunction with a total or indirect bilirubin test. |
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What does a decreased haptoglobin level mean?
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When haptoglobin levels are decreased, along with an increased reticulocyte count and a decreased RBC count, hemoglobin, and hematocrit, then it is likely that you have some degree of hemolytic anemia.
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If haptoglobin is normal and reticulocyte count is increased?
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If the haptoglobin is normal and the reticulocyte count is increased, then RBC destruction may be occurring in organs such as the spleen and liver. Because the freed hemoglobin is not released into the bloodstream, the haptoglobin is not consumed and so is normal.
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What if haptoglobin and reticulocyte levels are normal?
|
If the haptoglobin concentrations are normal and the reticulocyte count is not increased, then it is likely that the anemia present is not due to RBC breakdown.
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Haptoglobin is considered an “acute-phase” protein; this means that it will be elevated in many inflammatory diseases, such as ulcerative colitis, acute rheumatic disease, heart attack, and severe infection. This can complicate the interpretation of the haptoglobin results. Haptoglobin testing is not generally used to help diagnose or monitor these conditions.
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Haptoglobin levels may be affected by massive blood loss and by conditions associated with kidney dysfunction, as well as liver disease.
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What does haptoglobin do?
|
Haptoglobin combines with free plasma hemoglobin, preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin, while making the hemoglobin accessible to degradative enzymes.
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Hereditary SPHEROCYTOSIS [wiki]
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Hereditary spherocytosis is a genetically-transmitted (autosomal dominant) form of spherocytosis, an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped (Donut-Shaped), and therefore more prone to hemolysis.
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hereditary SPHEROCYTOSIS
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Defect in RBC MEMBRANE PROTEIN composition that causes small, donut shaped cells w/ HIGH concentrations of Hgb. They are less flexible, hence break easily in water. Destroyed by spleen.
Increased HEMOGLOBIN concentration means MCH up (weight) & MCHC up (concentration). **the cells are small spheres w/ the SAME amount of Hgb! |
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the spleen's hemolysis results in observational symptoms of fatigue, pallor, and jaundice.
The spleen's hemolysis results directly in varying degrees of anemia and hyperbilirubinemia, which in turn result in symptoms of fatigue, pallor, and jaundice. |
Hereditary spherocytosis
spleen destroys inflexible little suckers that have the Hgb level of normal sized cells |
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Describe a patient w/ hereditary spherocytosis
|
Fatigue, pallor, and jaundice ~ Chronic symptoms include anemia, increased blood viscosity, and splenomegaly, a potentially life-threatening enlargement of the spleen due to its increased activity. Furthermore, the detritus of the broken-down blood cells—unconjugated or indirect bilirubin--accumulates in the gallbladder, and can cause pigmented gallstones or "sludge" to develop. I
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Describe smear appearance of hereditary spherocytosis (hemolytic anemia subtype)
|
In a peripheral blood smear, the abnormally small red blood cells lacking the central pallor as seen in non-hereditary spherocytosis is typically more marked in hereditary spherocytosis.
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Hereditary ELLIPTOCYTOSIS
|
Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the sufferer's erythrocytes (i.e. red blood cells) are elliptical rather than the typical biconcave disc shape. It is one of many red-cell membrane defects. In its severe forms, this disorder predisposes to haemolytic anaemia. In camelids, elliptocytosis is normal.
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Because it can confer resistance to malaria, some subtypes of hereditary elliptocytosis are significantly more prevalent in regions where malaria is endemic
|
A clinically significant haemolytic anaemia occurs only in 5-10% of sufferers, with a strong bias towards those with more severe subtypes of the disorder.
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These mutations have a common end result; they destabilise the cytoskeletal scaffold of cells. This stability is especially important in erythrocytes as they are constantly under the influence of deforming shear forces. As disc-shaped erythrocytes pass through capillaries, which can be 2-3 micrometres wide, they are forced to assume an elliptical shape in order to fit through. Normally, this deformation lasts only as long as a cell is present in a capillary, but in hereditary elliptocytosis the instability of the cytoskeleton means that erythrocytes deformed by passing through a capillary are forever rendered elliptical.
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These elliptical cells are taken up by the spleen and removed from circulation when they are younger than they would normally be, meaning that the erythrocytes of people with hereditary elliptocytosis have a shorter than average life-span (a normal person's erythrocytes average 120 days or more).
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Because the spleen breaks down old and worn-out blood cells, those individuals with more severe forms of hereditary ______________ can have a splenomegaly, which causes a worsening of the signs and symptoms of their anaemia.
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elliptocytosis
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an anemia (of macrocytic classification) that results from inhibition of DNA synthesis in red blood cell production
|
Megaloblastic anemia
|
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|
a condition where the body converts iron into unused ferrin, causing a drop in hemoglobin production, and as a result; decreased red blood cell production and count. This is caused by a natural defense mechanism initiated by an inflammatory response in response to the underlying chronic disease.
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ACD
Anemia of Chronic Disease |
|
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Beta-thalassemia
|
autosomal dominant blood condition that results in the reduction of hemoglobin production. The cause for the disorder is related to a genetic mutation of the HBB gene. This gene is responsible for providing the instructions to produce beta-globin; one of the major components of hemoglobin. The two classification types of beta thalassemia are thalassemia major (also known as Cooley's anemia) and thalassemia intermedia
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A type of hemolytic anemia where hemoglobinuria results in the morning
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PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PNH: (also known as Marchiafava-Micheli syndrome) is a rare, acquired anemia of hematopoietic stem cell disorder = Pancytopenia where RBC's are unusually sensitive to COMPLEMENT FIXATION causing LYSIS
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genetic disease with an incidence of 1 per 350,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa
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FANCONI anemia
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Hemolytic paroxysmal nocturnal hemoglobinuria
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HEMATOPOIETIC STEM CELL PROBLEM, not an RBC membrane disorder like elliptocytosis or spherocytosis.
Bone MARROW makes all 3 cell types BAD = PANCYTOPENIA COMPLIMENT-FIXATION sensitive RBC's lyse easily BLOOD IN URINE in morning = hemoglobinuria, often 1st sign |
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LAB for HPNH
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~low hemoglobin
~raised lactate dehydrogenase ~raised reticulocytes (trying to ~replace destroyed ones) ~raised bilirubin (breakdown product of Hgb) ~decreased levels of haptoglobin *coomb's test negative b/c hemolysis not caused by antibodies but by stem cell disorder |
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Types of hemoglobinopathies that are hemolytic due to a disorder in the formation of the Hgb itself:
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1. Sickle cell anemia
2. Thalassemia a. Major/Cooley's b. Beta thalassemia c. Minor thalassemia |
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The sickling occurs because of a mutation in the haemoglobin gene. Life expectancy is shortened, with studies reporting an average life expectancy of 42 in males and 48 in females.
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Hemolytic SICKLE CELL anemia
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Hemoglobinopathy
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Hemolysis due to Hb disorder
(sickle cell and thalassemias) *Structure of 1 of 4 types of globin chains formed is abnormal, usually d/t substitution of a single a.a. *derived by ELECTROPHORESIS = positions of migration on cellulose acetate gel |
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Sickle cells are?
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rigid and shaped like sickles, hence get caught in vessels and promote thrombii - severe pain, infarction, ischemia from plugged capillaries in vital organs of kidney, spleen and brain.
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Why does the cell go sickle?
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Decreased oxygen tension causes Hgb to crystalize and precipitate out, causing sickling of cell. Makes cell rigid and trauma drama prone.
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Patient presentation during a sickling crisis
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BONE pain (ischemia)
ABDOMINAL pain (secondary) |
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genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin. This can cause the formation of abnormal hemoglobin molecules, thus causing anemia
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Thalassemia
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Thalassemia is a group of inherited ________ anemias, characterized by defective ____ synthesis.
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MICROCYTIC
HEMOGLOBIN *deletion of genes controlling Alpha or Beta globin chain. Rate of synthesis is decreased so person FATIGUED. |
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Hemolysis due to ENZYME DEFECTS
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1. Pyruvate kinase deficiency
2. Glucose-6-Phosphate dehydrogenase |
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the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.
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Erythrocytes manufacture ATP through glycolysis. A deficiency in pyruvate kinase, the enzyme that potentiates the last step of glycolysis (phosphoenolpyruvate converted to pyruvate), results in red blood cells (RBCs) with decreased energy.
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Pyruvate kinase deficiency
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RBC's use ATP to maintain flexibility of membrane and ATP synthesis requires several enzymes. When pyruvate kinase is missing from glycolysis step, a CHRONIC HEMOLYSIS develops. EXACERBATED by pregnancy, viral infections and acute illness.
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HEMOLYTIC labs (all)
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1. increased reticulocytes (d/t increased RBC production in the face of hemolysis)
2. decreased haptoglobulin 3. increased bilirubin 4. increased LDH |
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a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. ________deficiency is the most common human enzyme defect. Individuals with the disease may exhibit nonimmune hemolytic anemia in response to a number of causes, most commonly infection or exposure to certain medications or chemicals
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G6PD hemolytic anemia
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G6PD hemolytic anemia
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G6PD is part of monophosphate shunt. ASYMPTOMATIC w/ NORMAL CBC unless illness induced.
FAVISM = Hannibal Lector likes VICINE, ISOURAMIL and CONVICINE HEINZ BODIES present [inclusion bodies] |
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the most common feature of AUTOIMMUNE hemolytic anemias
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presence of AUTO-ANTIBODIES TO ANTIGENS ON RBC'S
[body attacks its own RBC's] |
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The binding capacity is the
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number of open binding sites on any transferrin molecule. If there are more sites open, the capacity goes up. So with a normal amount of transferrin molecules, the more iron saturation, the less capacity and vice versa.
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what happens if something lowers the number of transferrin molecules but iron saturation remains normal?
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As the transferrin protein goes down, the capacity goes down, not because there are fewer binding sites available on any given transferrin molecule, but because the number of molecules is reduced. Serum iron then can look low when in fact there is plenty of iron, but less iron carrier.
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Think of it like one of those trucks that carry cars. The truck is the transferrin molecule and the cars it carries are iron. Fewer cars on the truck, more capacity for cars. Fewer trucks on the road, lesser carrying capacity – not for lack of cars, but for lack of trucks.
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Fewer trucks on the road, lesser carrying capacity – not for lack of cars, but for lack of trucks.
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