2nd semester Lab Dx Unit 1
Terms
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- Site of iron absorption
- Duodenum
- Cells which regulate iron absorption
-
Mucosal (of duodenum)
if iron deficient iron passed to body, if not it may be sloughed back into gut - 3 stages of iron deficiency disease
-
1 iron dificiency without anemia (limited stores)
2 Iron limited hematopoiesis (production of microcytic cells as body runs out of iron)
3 Iron deficiency anemia - Hypocrhomic anemia: differential diagnosis (7)
-
1 Iron deficiency--95%
2 beta thalassemia trait
3 Sideroblastic anemia
4 Lead poisoning
5 Anemia of chronic disease
6 Alpha thalassemia
7 Hypercuprinemia - Lab Characteristics of beta thalassemia trait (3)
-
1 hypochromic anemia
2 iron studies normal
3 basophilic stippling - Lead poisoning lab characteristics (2)
-
1 hypochromic
2 coarse basophilic stippling - Peripheral smear w/ iron deficiency (5)
-
1 hypochromic
2 anisocytosis
3 poikiliocytosis
4 +/- target cells
5 NO basophilic stippling -
Serum iron vs TIBC in
Iron deficiency -
Iron is low
TIBC is high -
Serum iron vs TIBC in
anemia of chronic disease -
iron is low
TIBC is low - iron deficiency is 95% certain if Fe/TIBC is?
- < 10%
- if Fe/TIBC 10-30%, then
- iron deficiency must be distinguished from anemia of chronic disease
- If ferritin <10, then
- iron deficiency
- If ferritin 10-30, then
- possible iron deficiency
- Clinical features of iron deficiency (4)
-
1 Pallor, conjunctival pallor (not specific--signs of anemia)
2 koilonychias (spoon nails)
3 angular chelosis
4 glossitis - Treatment of iron deficiency
-
Ferrous sulfate 300 mg t.i.d.
--60 mg of elemental iron per pill
--NO enteric coated iron - Duration of iron deficiency treatment
- until hematocrit is normal, then 3-6 months to replete marrow stores
- Treatment of iron deficiency with malabsorptive patients
- IM injection (not IV) of iron
- Conditions with decreased soluble transferrin receptor
-
conditions of erythroid hypoplasia, such as aplastic anemia and red cell aplasia
anemia of chronic disease - conditions with increased soluble transferrin receptor
-
conditions of erythroid hyperplasia, such as chronic hemolytic anemia
in iron deficiency - soluble transferrin receptor use for differential of iron deficiency and anemia of chronic disease
-
increased in iron deficiency
decreased in anemia of chronic disease
--useful when iron, TIBC, and ferritin are borderline -
soluble transferrin receptor/log ferritin
in iron deficiency vs anemia
of chronic disease
(#?) -
iron deficiency: >4
anemia of chronic disease: <1 - screening test for hemochromatosis
-
transferrin saturation
NOTE: high saturation will be seen in aplastic anemia b/c of inability to use iron - Mutations associated with hemochromatosis
-
C282Y, H63D, S65C
NOTE: C282Y +/+ confirms dx - definition of megaloblastic
- increase in early erythroblasts in the bone marrow
- most common causes of macrocytic anemia
-
folate deficiency and B-12 deficiency
NOTE: these two are also megaloblastic b/c they cause slow DNA production and therefore slow maturation - Folate role in DNA synthesis
- methyl donor in thymidine synthesis
- Where is folate absorbed
- the jejunum
- folate body stores vs B12 body stores duration
-
folate lasts few months, B12 for 3 years
Thus, if diet interupted folate defiency first - Drug which causes folate malabsorption
- dilantin (aka phenytoin), anti seizure drug
- Conditions of increased folate need
- pregnancy and hemolytic anemia
- Tests specific for folate deficiency (2)
-
red cell folate
serum folate (not as good, since one meal may raise serum, but not red cell folate) - Blood smear and marrow in folate deficiency
-
smear: macrocytic with hypersegmented neutrophils
megaloblastic marrow - Therapy for folic acid deficiency
- Folic acid 1 to 5 mg/day
- Danger of folic acid replacement therapy w/o B12 evaluation
- Blood counts may correct, but neurologic problems may progress
- Role of B-12
- via role in methionine synthesis, converts methyl-THF to THF
- steps of B12 absorption (3)
-
1 stomach: binds to R factors, protects it from acid degradation.
2 Duodenum: pancreatic enzymes free B12 from R binders, binds to intrinsic factor (from parietal cells)
3 B12-IF absorbed by terminal ileum - Conditions associated with pernicious anemia (5)
-
1 premature gray hair
2 Vitiligo
3 Thyroid disease
4 Hypoparathyroidism
5 Gastric atrophy w/ achlorhydria -
Causes of B12 deficiency
Diet (1) - vegan diet, no eggs, cheese, or meat
-
Causes of B12 deficiency
Gastric (5) -
1 pernicious anemia
2 Decreased IF
3 Atrophic gastritis
4 gastrectomy
5 Zollinger-Ellison (inc acid, no binding to IF) -
Causes of B12 deficiency:
Intestinal (4) -
1 regional enteritis
2 celiac disease
3 pancreatic disease (no enzymes to liberate from R binders)
4 blind loop
--also fish tapeworm, rare - Clinical features of B12 deficiency (5)
-
1 pallor w/ lemon yellow skin (due to hemolysis in marrow)
2 Glossitis (beefy tongue, megaloblastic tongue)
3 paresthesia of hands and feet, position and vibration sense loss
4 combined system disease (demylenization of dorsal and lateral columns)
5 other neuro: somnolence, altered taste and smell, scotomata, dementia - Dx of b12 deficiency based on serum B12
-
<100 diagnostic
100-200 suspicias
>200 normal - test to establish diagnosis and pathophysiology of B12 deficiency
-
Schilling test
Give radioactive B12 by mouth
2 hrs later, give a flushing dose of B12 I.M. (1 mg)
measure urine radioactivity vs feces. If in urine, then it was absorbed.
Repeat with oral intrinsic factor - Therapy for B12 deficiency
- 1000 micrograms/day x 2 weeks, then weekly until hematocrit is normal. Brisk reticulocytosis occurs within a week.
- METHYLMALONIC ACID TEST, why?
- Since B12 is required to convert methylmalonate to succinate, some physicians advocate testing for urine methylmalonic acid as a diagnostic test for B12 deficiency
- MACROCYTIC ANEMIA – the full differential diagnosis(8)
-
1 Folate and B12 deficiency are 95% or more of cases
2 Chemotherapy with antimetabolites
3 Alcohol – even in the absence of folate deficiency
4 Liver disease
5 Hypothyroidism
6 Myelodysplasia (usually a normocytic anemia, can be macrocytic)
7 INCREASED RETICULOCYTES – Each 1% elevation of retics raises the MCV 1 point.
8 Myeloma and dysproteinemias (artefactual). Cells clump together and the machine counts two cells as one. - Differential: anemias of bone marrow failure(6)
-
1 APLASTIC ANEMIA
2 PURE RED CELL APLASIA
3 MYELOFIBROSIS
4 MYELODYSPLASIA
5 MYELOPHTHISIC ANEMIA
6 ANEMIA OF CHRONIC DISEASE - Dx of aplastic anemia
- bone marrow biopsy showing aplasia
- tx of aplastic anemia (2)
-
Immune therapy with anti-lymphocyte serum, cyclosporine, and cortiocosteroids
bone marrow transplant - Pure red cell aplasia dx
-
Low hematocrit
LOW (or zero) reticulocytes
NORMAL wbc and platelets
Marrow: NO red development, everything else normal - Two possible causes and one association of pure red cell anemia
- Cases may be drug related (dilantin), or may occur post infection (with parvovirus) or in association with thymoma.
- Tx of pure red cell aplasia
-
corticosteroids, immunosuppressive therapy
blood transfusions, iron management.
very survivable - myelofibrosis (aka agnogenic myloid metaplasia) dx
-
splenomegaly (can be MASSIVE)
teardrop cells on blood smear give a hint. white count usually normal--can be elevated, resembling CML
biopsy showing fibrosis is diagnostic (aspirate often "dry tap") - types of myelodysplasia with high rate of leukemia development
-
RAEB--refractory anemia with excess blasts
RAEB-T--refractory anemia with excess blasts in transformation - myelodysplasia dx
-
anemia
Pathologic sideroblasts containing more than five iron granules per cell
low reticulocyte count - MYELODYSPLASIA
- group of clonal disorders, present with anemia, half of the patients eventually die of leukemia, others have marrow failure without leukemia at the time of death
- MYELOPHTHISIC ANEMIA
- Anemia due to bone marrow replacement usually by a tumor
-
Diagnosis?
RBC smear: Normal
Marrow: Hypoplasia
WBC: Decreased
Differential: Normal or decreased polys
Platelets: Decreased - Aplastic Anemia
-
RBC smear Normal
Marrow No RBCs
WBC Normal
Differential Normal
Platelets Normal - Pure Red Cell Aplasia
-
RBC smear Teardrops
Marrow Fibrosis
WBC Variable
Differential Normal or increased Myelocytes and other immature WBCs
Platelets Normal or Low - Myelofibrosis
-
RBC smear Normal
Marrow Ineffective RBC Production
WBC Variable, normal or low
Differential Normal, Increased blasts when advanced
Platelets Normal: Decreased in advanced stages - Myelodysplasia
-
RBC smear Nucleated RBCs
Marrow Infiltration by tumor or other process
WBC Variable
Differential Variable: normal or may resemble myelofibrosis (inc myelocytes and other immat. Wbc's)
Platelets Decreased - Myelophtisis
-
RBC smear Normal
Marrow Normal
WBC Normal
Differential Normal
Platelets Normal - Anemia of Chronic Disease
- drug that delays progression of myelodysplasia to acute leukemia
- Vidaza
- Cytogenetics more likely to be abnormal in which two myelodysplasias
- RAEB (Refractory anemia with excess blasts) and RAEB-T (Refractory anemia with excess blasts in transformation)
- subtypes of myelodysplastic syndrome
-
Refractory anemia RA
Refractory anemia with ringed sideroblasts RARS
Refractory anemia with excess blasts RAEB
Refractory anemia with excess blasts in transformation RAEB-T
Chronic myelomonocyctic leukemia CMML - most prominent feature of myelodysplastic syndromes ("often")
- Anemia
- cell lineages involved in myelodysplastic syndromes
- Red cells, granulocytes and platelets are involved
- Therapies that do not work for myelodysplasia
-
13 cis retinoic acid
Corticosteroids
Androgens
Low dose cytosine arabinoside - interpretation of reticulocyte count vis a vis hemolytic anemia
-
increased in hemolytic anemia, does not PROVE hemolysis
Bleeding causes increased reticulocyte count
NOTE: Concommittant problem limiting red cell production (i.e. parvo virus injury of marrow) can lower rets - How do you know if anemia is hemolytic? (5)
-
1 Reticulocyte count is elevated
2 Bilirubin is up and unconjugated
3 LDH (lactic dyhydrogenase) will be elevated
4. HAPTOGLOBIN: down (if intravascular, not spleenic hemolysis)
5. Decreased chromium 51 survival (rarely measured) - Classes of hemolysis (where is the defect?) (4)
-
1 Outside the red cell (IgG "warm", IgM "cold", hypersplenism, other)
2 Membrane defects (spherocytosis)
3 Enzyme defects (90% G6Pd--oxidant sensitive; pyruvate kinase 10%)
4 Abnormal hemoglobin - Dx of immune hemolytic anemia
-
1 Positive Coombs test (direct version)
2 lab determines which type of antibody or complement (IgG warm, IgM cold) - Treatment of warm antibody hemolysis (3)
-
1 corticosteroids. if fails..
2 splenectomy. if fails..
3 immunosuppression - Treatment of cold antibody hemolysis (3)
-
1 keep patient warm, blood products warm
2 Plasmapheresis (b/c IgM intravascular)
3 Cytotoxic therapy
--NO splenectomy or steroids - conditions associated with IgG hemolysis (3)
-
1 systemic lupus
2 chronic lymph leuk
3 lymphoma - conditions assoc with IgM hemolysis (3)
-
1 mycoplasma infection
2 infectious mono
3 Waldenstrom's macroglobunemia - 3 mechs of drug caused hemolytic anemia
-
1.Antibody against a drug which binds to the membrane when present in very high concentration – occurs with high dose pencillin.
2.Neoantigen formation, the antibody is against a drug/membrane complex This is the most common mechanism of drug related hemolytic anemia
3.Aldomet mechanism. Autoimmune hemolytic anemia like idiopathic process occurs. No need for drug to be present. - chinese:spherocytosis
-
çƒå½¢çº¢ç»†èƒžç—‡
qiúxÃng hóngxìbÄo zhèng
"spherical RedCell disease"
spherocytosis - كرية Øمراء كروية
-
Red globule spherical
spherocytosis -
çƒå½¢çº¢ç»†èƒžç—‡
qiúxÃng hóngxìbÄo zhèng -
qiúxíng hóngxìbāo zhèng
"spherical RedCell disease"
spherocytosis - spanish: spherocytosis
- esfirocitosis
- arabic spherocytosis
-
كرية Øمراء كروية
Red globule spherical -
WARM ANTIBODY hemolytic anemia
1 molecule bound to cell?
2 where macrophage binding?
3 which organ injured?
4 Injury extra or intra vasc?
5 Rx? -
1 IgG
2 Macros bind in cords of Billroth in spleen
3 Splenic destruction
4 extravascular
5 Corticosteroids, splenectomy -
COLD ANTIBODY hemolytic anemia
1 molecule bound to cell?
2 where macrophage binding?
3 which organ injured?
4 Injury extra or intra vasc?
5 Rx? -
1 Complement--fixed by transient IgM
2 Liver
3 Hepatic injury
4 Intravascular
5 Keep warm, plasmapheresis, cytoxic chemotherapy - Hereditary spherocytosis most common defect
- spectrin (membrane protein)
- hereditary spherocytosis Rx
- splenectomy
- Diagnosis of Sickle cell
-
Hemoglobin electrophoresis – mostly S, some F, some A2, no A
NOTE: If A is present it is either sickle thalassemia (S>A) or sickle trait (A>S) -
血红蛋白
xuèhóng dà nbái -
xuèhóng dànbái
bloodred eggwhite (protein)
hemoglobin - screening test for sickle cell diesease or trait
- sodium metabisulfite
- Blood smear of thalassemia (5)
-
1 Microcytic anemia
2 hypochromia
3 anisocytosis
4 target cells
5 basophilic stippling
NOTE: basophilic stippling does NOT occur in Fe deficiency - Thal trait vs Fe deficiency
- Iron normal, iron binding normal, Hgb A2 elevated (3.5% vs 2.5%), basophilic stippling
-
è‘¡è„ç³–å…磷酸鹽脫氫酶缺ä¹ç—‡
pútaotáng liù lÃnsuÄnyán tuÅ qÄ«ng méi quÄ“fá-zhèng -
pútaotáng liù lÃnsuÄnyán tuÅ qÄ«ng méi quÄ“fá-zhèng
grape-sugar 6 phosphorous-acid-salt break hydrogen enzyme(ferment) lack-disease
Glucose-6-phosphate dehydrogenase deficiency - ttp, who cares?
-
Without treatment 80% die, with treatment, plasmapheresis,
80-90% are cured. - اÙسْتÙخْراج بلازما
- plasmapheresis
-
血浆å–出法
xuèjiÄng qÇ”chÅ« fÇŽ -
xuèjiÄng qÇ”chÅ« fÇŽ
blood-syrup takeout method
plasmapheresis - Mechanism of PAROXYSMAL COLD HEMOGLOBINURIA
-
in cold, IgG binds to rbc's. when warm, cells lyse.
Coomb's negative for IgG, + for complement.
Cross reactivity w/ syphilis? - erythrocytosis differential
-
pseudoerythrocytosis--low plasma volume
secondary erythrocytosis--"reactive" to erythropoietin--could be physiologic or abnormal
polycythemia vera - abnormal causes of erythropoietin elevation (6)
-
1 renal disease
2 CNS disease
3 liver disease
4 cushings
5 adrenal adenoma
6 uterine fibroids - diagnostic criteria of polycythemia vera
-
Red cell mass (volume) Males >36 ml/kg; Females > 32 ml/kg
Oxygen saturation >92%
bone marrow with trilineage hyperplasia - 3 steps of evaluation of elevated hematocrit
-
1 if hematocrit >60, then not pseudoerythrocytosis. If < 60, start with red cell volume and plasma volume.
2 2ndary erythrocytosis vs. P vera. Test for common 2ndary causes (hypoxia, CO) Perform
A Complete Blood Counts
B Arterial blood gases with CO level
C Bone marrow aspiration and biopsy
3 If no diagnosis, then look for exotic causes:
Perform
A Renal ultrasound
B Pelvic and abdomen CT
C Oxygen dissociation (abnormal hemoglobin)
NOTE: phlebotomy can treat P Vera and 2ndary so not always necessary to definitively diagnose - Treatment of pseudoerythrocytosis
- Volume repletion
- Treatment of secondary erythrocytosis
-
treat underlying disorder (hypoxia, etc)
phlebotomize to hematocrit under 48 - Tx of polycythemia vera
-
Phlebotomy <70
P32 (radioactive phosphorus) for older - A1 and A2 diagnostic criteria of polycythemia vera
-
A1: Raised red cell mass (volume) more than 25% above mean normal predicted value, or hematocrit > 60 in males or > 56 in females
A2: Absence of cause of secondary erythrocytosis - PURE RED CELL APLASIA
- An autoimmune disease in which an antibody to early erythrocytes is present.
-
ANEMIA OF BONE MARROW FAILURE
common lab features -
1 normocytic anemias
2 low reticulocyte count
3 crucial diagnostic test in this situation is the bone marrow aspirate/biopsy - APLASTIC ANEMIA
-
initially thought to represent toxic, irreversible damage to bone marrow stem cells
low hematocrit, platelet, granulocytes
immunosupression often works, so autoimmune - MYELOFIBROSIS
- A clonal myeloproliferative disorder in which a stem cell exists which grows better outside the marrow, in the spleen
- ANEMIA OF CHRONIC DISEASE
-
1 A non-specific term used to describe those cases in which a chronic condition is associated with an anemia for which no specific cause can be found.
2 Inflammation could mute response to erythropoietin - low vs high reticulocyte count in anemic patient. MCV significance
-
If high hemolytic or blood loss
If low, anemia of bone marrow failure--will increase MCV - Tests for iron deficiency
-
1 Peripheral smear--hypochromic w/ anisocytosis and poikilocytosis, NO basophilic stippling
2 Serum iron/serum iron binding capacity. Low for iron deficiency
3 Serum ferritin, proportional to body stores.
4 Bone marrow definitive, but $ and ivasive - most common cause of iron deficiency
- Bleeding is most common cause of this anemia
- what is the biochemical problem of sickle cell anemia
- Amino acid substitution as 6 position of beta chain, glutamine to valine
- Most common anemia(s) with following morphology: macrocytic
- Morphology associated with: Folate deficiency
- Most common anemia(s) with following morphology: Normocytic (w/ low reticulocytes)
- Morphology associated with: Pure red cell aplasia & Myelodysplasia
- Most common anemia(s) with following morphology: Hypochromic
- Morphology associated with: Iron deficiency
- Most common anemia(s) with following morphology: microcytosis
- Morphology associated with: Thalassemia
- Most common anemia(s) with following morphology: Dimorphic micro and macrocytes
- Morphology associated with: sideroblastic anemia
- Most common anemia(s) with following morphology: Schistocytes
- Morphology associated with: Microangiopathic hemolytic anemia
- Most common anemia(s) with following morphology: Target cells
- Morphology associated with: Iron deficiency, splenectomy, thalassemia
- Most common anemia(s) with following morphology: Teardrop cells
- Morphology associated with: Myelofibrosis
- Morphology associated with: Folate deficiency
- Most common anemia(s) with following morphology: macrocytic
- Morphology associated with: Pure red cell aplasia & Myelodysplasia
- Most common anemia(s) with following morphology: Normocytic (w/ low reticulocytes)
- Morphology associated with: Iron deficiency
- Most common anemia(s) with following morphology: Hypochromic
- Morphology associated with: Thalassemia
- Most common anemia(s) with following morphology: microcytosis
- Morphology associated with: sideroblastic anemia
- Most common anemia(s) with following morphology: Dimorphic micro and macrocytes
- Morphology associated with: Microangiopathic hemolytic anemia
- Most common anemia(s) with following morphology: Schistocytes
- Morphology associated with: Iron deficiency, splenectomy, thalassemia
- Most common anemia(s) with following morphology: Target cells
- Morphology associated with: Myelofibrosis
- Most common anemia(s) with following morphology: Teardrop cells