Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
82 Cards in this Set
- Front
- Back
|
How many % of world population are anemic?
|
30%
|
|
|
Anemia definition and cut off?
|
Anemia is reduction in total RBC mass; can be due to lower hematocrit, Hb level or RBC number. Lower than 2SD considered anemic (F: Hb<12g/dL, Hct <36%; M: Hb<13.5g/dL, Hct<41%)
|
|
|
RBC diameter, int/ext factors needed for survival?
|
RBC 8um cross (about Lymp Nuc size) but squeezable; Int: need to maintain shape and osmolarity; Ext: need to to avoid circulating factors (AB, toxin), spleenic destruction, vascular destruction.
|
|
|
Hemoglobin structure & Fe state for O2 binding? Saturation curve change for high altitude?
|
Hb is made of 2 alfa, 2beta chains; need Ferrous for O2 binding; curve shifts right for low oxygen.
|
|
|
What are the five metabolic processes in RBC?
|
The five metabolic processes in RBCs are: Glycolysis, Pentose shunt, Glutathione reduction, Ion pump, Methemoglobin Fe reduction.
|
|
|
What are the five possible physiological process that can causes of Anemia?
|
The four processes are kidney disorder, EPO unable to stimulate BM, decreased production or release from BM, short RBC survial, loss of RBC via bleeding
|
|
|
Reticulocyte morphology, stain?
|
Reticulocytes are slightly larger and bluer, they can still synthesize some Hb; supervital stain stains them.
|
|
|
What's the normal reticulocyte count? What's the corrected count?
|
Normal Recticulocyte count is 0.5-2%; correct by RecCountx(sample Hct/Normal Hct)
|
|
|
What 4 things can causes diminished production to give anemia?
|
Diminished production anemia can be caused by: Lacking Fe, folate, B12; MW can't use Fe (chronic disease); lacking EPO (kidney disease); Hypoplastic/aplastic marrow
|
|
|
Finidings and mechanisms of Marrow Hypoplasia or aplasia anemia?
|
In BM hypoplasia/aplasia, BW has low cellularity and low WBC & RBC level; often stem cell disorder or idiopathic.
|
|
|
What are the approximate cut off lines for mild, moderate and severe anemia?
|
Mild anemia Hb>10mg; Moderate anema Hb:8-10; Severe Hb<8mg
|
|
|
How does conjunctiva change in anemic patients?
|
Anemic conjunctiva is more pale.
|
|
|
What are the normla values for MCV and RDW?
|
MCH: 80-100fL; RDW: 11.5-14.5
|
|
|
What the difference between leptocytes and hypochromasia? Basophilic stippling vs Pappenheimer bodies?
|
Leptocytes shows a buldge in the midde of RBC (increased membrane to Hb ratio); hypochromasia just has a bigger center concavity. Basophilic stippling is more diffused than Pappenheimer bodies.
|
|
|
What are the 4 possible differentials for microcytic anemia? What are other diagnostic features of these?
|
Microcytic anemia: Fe deficiency (hypochromasia), thalassemia (hypo, poly, B stippling), sideroblastic anemia (hypo & B stippling), chronic disease/inflammation anemia.
|
|
|
What are the 5 possible differentials for normocytic anemia?
|
Normocytic anemia: Sickle cell, hemolytic anemia (microspherocytes), blood loss, chronic disease, mild Fe deficiency
|
|
|
What are the 3 possible differentials for macrocytic anemia? What other feature often accompnay macrocytic anemia? How can the different types of macrocytic anemia be distinguished?
|
Macrocytic anemia: B12 deficiency, folate deficiency, myelodysplastic syndrome; high RWD often seen as well; hypersegmented PMN indicates megaloblastic anemia.
|
|
|
What are the morphological features of hemolytic anemia?
|
Hemolytic anemia features microspherocytes and polychromatic RBCs (which reflects compensation for increased RBC destruction).
|
|
|
Fe anemics
|
|
|
|
What the normal total body iron amount and where are they distributed? What's the normal daily intake and loss?
|
Normal body iron: 45mg/kg M, 35 mg/kg F; usually 70% Fe in Hb, 20% in storage; daily intake and loss about 1mg
|
|
|
Describe the pathway of Fe from food to Hb?
|
Enterocytes absorb Ferrous Fe via DMT1 (dival metal transporter); it can stored in Ferritin or exported as Ferroportin; in plasma Fe binds to Transferrin, which is taken by TFNR on erythroblast and clathrin pit. Ferrous Fe is then released.
|
|
|
How does Iron Response Protein function in the body?
|
Iron Response Protein (IRP) downregulates Ferritin protein and upregulates Transferrin at LOW Fe condition; it does the opposite at High Fe ocndition.
|
|
|
What are the 2 big categories and 5 subtypes of Fe deficiency in human?
|
Fe decifiency can be due to either inadequate supply (Poor nutriton, absorption problem) OR Increased demand (blood loss, growth, pregnancy)
|
|
|
Who are susceptible to Fe nutritional defiency? How can Fe uptake be increased?
|
Young child, teens, extreme dieters and low SES are prone to nutritional Fe deficiency; Fe absorption can be increased by using animal instead fo plant hemes and ascorbic acid (VitC)
|
|
|
Who are at risk for decreased gut Fe absorption of Fe?
|
Tea/coffee/bran consumers, those with disrupted GI tube (Crohn's, Celiac disease) and those with achlorhydria at susceptible to decreased gut Fe absorption.
|
|
|
What are two chronic hemoglobinuria illnesses that can contribute to blood loss anemia?
|
Mechanical heart valve and Paroxymal nocturnal hemoglobinuria both contribute to blood loss.
|
|
|
What are some signs and symptoms of iron deficiency?
|
Iron deficiency symptoms: Pallor, weakness, fatigue, headache, irritability, palpitations, pagophagia, koilonychia, blue sclera, beeturia, angular stomatitis
|
|
|
What are the three stages of Iron deficiency and what are the features of each?
|
Reduced iron storage (low marrow iron and ferritin); Depleted iron storage (low TIBC, low plasma Fe, low transferrin saturation, hi soluable TFNR); Iron deficiency anemia (low Hb, low MCV)
|
|
|
What are lab features of Fe decifient anemia (Hb, RBC, MCV, RWD, Reticu, Platelet)?
|
Fe deficiency shows: low Hb, low RBC, low MCV, High RWD (new and old mix), low Retic, low Platelet.
|
|
|
What are 6 biochemcial lab features of Fe deficient anemia?
|
Fe deficiency biochem evals show: low serum Fe, low Ferritin, low TFN saturation, high TIBC, high serum TFNR, high free erythrocyte protoporphyrin.
|
|
|
What are possible treatments for Fe deficiency?
|
Oral: oral ferrous sulfate, or slow release (less GI problem, but $$ and below duodenum release); Parenteral: for poor adherence, possible analphylaxis; RBC transfusion: only if immediate HF danger or bleeding.
|
|
|
What the response time for Fe treatment?
|
After Fe therapy, reticulocyte rises after 3-4 days and peaks at 5-7 days; Hb rises 0.25-0.4/day.
|
|
|
What are some non-hematological effects of Fe deficiency?
|
non-hematological effects of Fe deficiency include: GI (gastritis, achlorhydria, malabsorption), developmental changes, impaired immunity, low work performance and developmental effects.
|
|
|
What are the hematological features of anemia of chronic inflammation (In term of smear, reticulocyte and Ferritin)?
|
anemia of chronic inflammation shows micro/normocytic RBC, mild to moderate anemia and normal or low reticulocyte count. Ferritin count normal or increased (as opposed to Fe deficiency anemia).
|
|
|
What are the 3 primary pathophysiological features of anemia of chronic inflammation?
|
Anemia of chronic inflammation: Transfer of RES/enterocyte Fe to transferrin is defective; low Epo production/response; reduced RBC life span.
|
|
|
Where is Hepcidin made? What induces/inhibits its expression?
|
Hepcidin is made in liver and is induced by high Fe and Inflammaion; reduced by EPO drive, hypoxia and Fe deficiency.
|
|
|
What is the role of Hepcidin in iron metabolism?
|
Hepcidin can cause ferroportin degradation hence reduced Fe release from RES and enterocytes.
|
|
|
Megaloblastic anemia
|
|
|
|
What typically happens to N/C ratio as cells mature? What's one anemia where this feature is not observed? What's another feature of this types of anemia?
|
N/C ratio typically decreases as nuclei condenses in maturing cells; in megaloblastic anemia N/C ratio may fail to decrease, in addition, the PMNs may become hypersegmented.
|
|
|
What are 5 causes of megaloblastic anemia?
|
The five causes are: folate deficiency, cobalamin deficiency, acute megaloblastic anemia, drugs, and in born errors.
|
|
|
What biochemical step does Vit B12 catalyze? Why does it affect nuclei but not transcription?
|
Vit B12 (Cobalamin) is cofactor of MTHFR, which catalyzes changing methy-THF + homocysteine to THF + methionine; this pathway will eventually be used to turn dUMP to dTMP; hence only DNA (need Thymidine) will be affected.
|
|
|
How is Vit B12 absorbed by the body?
|
Parital cells in stomach produces Intrinsic Factor and R-binder, which better binds B12; in Duodenum and Jejunum pancreatic enzyme inactives R-binder so IF binds B-12; in Ileum IF-B12 is uptaken by Transcobalamin II. TCII brings B12 to liver and systemically.
|
|
|
What are three types of impaired absorption causes of Cobalamin deficiency:
|
Gastric cause (Pernicious anemia, gastrectomy, Zollinger-Ellison Syndrome); Intestinal causes (Crohn's disease, Blind loop syndrome (bacteria steals B12), Fish tapeoworm); Pancreatic insufficiency (no R-binder inactivation)
|
|
|
What is Schillings test?
|
Schillings Test is when radioactive Cobalamin is given to meglaoblastic anemia patients along with IF/Antibiotic/pancreatic extract/ovalbumen; urine radioactivity is used depend on the other factor given to indicate if Cobalamin is successfully absorbed.
|
|
|
What type of disease is pernicious anemia? What other disease can it associate with?
|
Pernicious anemia is an autoimmune disease and can coexist with other autoimmune diabetes such as thyroid disease and ulcerative colitis.
|
|
|
What are the signs and symptoms of megaloplastic anemia?
|
Megaloblastic anemia signs include: Tiredness, pallor, jaundice, CHF, epithelia lesions (tongue, mucosa, cervial lesions), infections and bleeding.
|
|
|
What types of abnormalities in Cobalamin defiency is irreversible? What are its features?
|
Combined system disease is a demylination disease that can cause: paresthesia of hands and foot, spastic ataxia, somnolence and megaloblastic madness.
|
|
|
How to treat Cobalamin defiency? How not to treat?
|
Cobalamin deficiency can be helped with B12, which shows reticulocytosis in 3-5 days; DON'T transfuse (causes hypervolemic HF); treating with folate may mask neurological problems.
|
|
|
How is Pernicious Anemia treated?
|
Pernicious anemia is treated by IM B12 injection, starting with 1g/day for 1-2wks and gradually waned to 1g/mth for life.
|
|
|
What are some general causes of folate deficiency?
|
Folate deficiency can be caused by: decreased uptake: poor nutrition, impaired absortion (sprue) or increased demands: pregnancy, increased cell turnover (hemolytic anemia)
|
|
|
What is the cause of acute megaloblastic anemia?
|
Acute Megaloblastic anemia is caused by Nitric Oxide exposure, which blocks MTHFR activity.
|
|
|
What are some of the drugs that can causes megaloblastic anemia?
|
The drugs that can cause megaloblastic anemia include: Dihydrofolate Reductase Inhibitors (Trimethoprim), Antimetabolites, Inhibitors of Deoxyribonucleotide synthesis, Anticonvulsants, OCP.
|
|
|
|
|
|
|
Hemoglobinopathy
|
|
|
|
What are the alpha/beta like genes and where are they located?
|
Alpha like (Chr 16): Zeta, alpha1, alpha2; Beta like (Chr 11): Epsilon, gamaG, gamaA, delta, beta
|
|
|
What are the compositions of embryonic, fetal and adult hemoglobins?
|
Embryonic (zeta2epsilon2), fetal (alpha2gama2), adult (a2b2, a2delta2)
|
|
|
For alpha and beta genes, what are more common, deletion or mutation?
|
For alpha deletion more common than mutation, for Beta mutation more common than deletion.
|
|
|
What are the types and symptoms of alpha gene deficiency?
|
Most trait (2-3 copies) normal, with slight hypochromatic microcytic anemia. Some (1 alpha) shows Hb H (beta4 don't release O2) shows moderate to severe hypochromic microcytic anemia.
|
|
|
What population has trans alpha thalasemia trait? Why is it important to know?
|
Most US blacks have trans, henc the chance of hydrops fetalis is low.
|
|
|
What types of beta thalasemias are there?
|
b/b0 or b/b+ are minor (5-7% Hb A2, microcytic); b+/b0 or b+/b+ are intermedia (micrcytic, Hb A2); b0/b0 is major (Cooley's, microcytic, Hb F, Hb A2)
|
|
|
What is the pathophysiology of alpha thalasemia? What medical treatment is actually harmful?
|
Alpha thalassemia creates Hb H, causing erythroid destruction both in BM and vasculature; mild anemia and ineffective hematopoesis results; hypoxic tissue cause EPO induced recticulocytosis; Transfusion with iron often causes Fe overload.
|
|
|
What is the pathophysiology of beta thalasemia?
|
in beta thalassemia, excessive alpha chians precipitate (Heinz bodies); causing severe anemia and massive extramedulllary hematopoesis (BM & spleen); recticulocytosis also exists.
|
|
|
Therapy for thalassemia?
|
PRBC transfusion, but risking infection and iron overload. Desferioxamine to remove Fe. BMT, hydrea to induce Fetal globin.
|
|
|
How are sickle cell trait differ from sickle cell disease?
|
Trait has BetaABetaS (AS) whereas disease has BetaSBetaS (SC) Hb.
|
|
|
Pathophysiology of the BetaS in sickle cell disease?
|
In BetaS, a point mutation causes Glu-Val change; deoxyed SC cause Val to bind in hydrophobic pocket and polymerize; repeated polymerization will cause permanent damage.
|
|
|
What are the hematological findings in Sickle cell syndromes?
|
In SS, 90% HbS, 10% HbF; in AS: 60% HbA, 40% S, if more A then alpha thalassemia, if less than beta thalassemia.
|
|
|
What are the four general pathological factors that contribute to Sickle Cell disease?
|
Sickle Cell: Rheology, RBC dehydration, Cellular adhesion, reduced NO
|
|
|
What are the acute life threatening complications of sickle cell? What is the spleen like in sickle cell disease?
|
Sickle cell complications include: acute chest syndrome, splenic sequestration crisis (fatal anemia), aplastic crisis (recticulocytopenia usualy due to parovirus), painful crisis. Sickle cell splenn is very small due to infarction.
|
|
|
What are some treatments for sickle cells?
|
Acute treat insulting factor, chronically throught BMT or hydrea induciton of fetal hemoglobin.
|
|
|
Leukocyte migration
|
|
|
|
What are various cell adhesion molecules and some general features?
|
Cadeherin (Ca+ homophilic, tissue architecture), Igs, selectins (only vascular cells, bind carbohydrates), integrins (alpha/beta heterodimers).
|
|
|
What molecules mediate the capture, slow and fast rolling of leukocytes? When are they made?
|
L-selectin on Leuko mediate capture and fast rolling; P-selectin on Endothelia cell mediate capture and fast rolling (stored); E-selectin on Endothelia then ends it by slow rolling (de novo synthesis)
|
|
|
What molecular changes occur in leukocyte activation? What about adhesion?
|
In leukocyte activation, beta2 integrin expression occurs (E-selectin induced), L selectin is shed and cell commits to leaving circulation. Integrin and Ig superfamily members play a part in adhesion.
|
|
|
Leukocyte adhesion deficiency I and II?
|
Type I lacks beta2 integrin, type II lacks E and P selectin.
|
|
|
Hemolytic anemia
|
|
|
|
Why is plasma yellow in color?
|
Plasma is yellow because bilirubin binds to albumin.
|
|
|
How is basophilic stippling different from Howell Jolly bodies? Heinz bodies?
|
Basophilic stipping areribo RNA while Howell Jolly are DNA. Heinz bodies is Hb precipitate (beta thala or G6PD deficiency)
|
|
|
What proteins in the blood bind to free Hb or heme?
|
Haptoglobin binds Hb; Hemopexin and albumin bind heme.
|
|
|
What are some lab evidences for hemolysis?
|
Hemolysis: increased retic count, increase bilirubin, decreased haptoglobin, marrow erythroid hyperplasia, decreased Cr51 RBC survival. Spherocytes if immune due to RES taking bites out of the RBC.
|
|
|
How are direct and indirect Coomb's test performed?
|
Direct coombs test for AB already bound to RBC; patient RBC is incubated with anti-Fc AB; clumping can occur; Indirect tests for serum anti-RBC AB, patient serum is incubated with test RBC first, then anti-Ig AB are added.
|
|
|
Cold reactive antibodies, features, tests and disease?
|
Cold reactivea antibodies are IgM that only binds when cold; can cause hemolysis in vivo due to complement fixation; Coomb's test for AB negative but positive to complement. Found in mycoplasma pneumonia and cold agglutinin disease.
|
|
|
G6PD deficiency mechanism, triggers and consequences?
|
G6PD deficiency is often triggered by infection or drugs (Primaquine for malaria), causing self-limiting hemolysis; can result in chronic non-spherocytic anemia; Heinz bodies are seen.
|
