• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/121

Click to flip

121 Cards in this Set

  • Front
  • Back
Q: What is the most common nutritional disorder in the world?
-iron deficiency is a common form of anemia and probably the most common nutritional disorder in the world
-most common in North American and European women of child bearing age as a result of bleeding
-6 – 8 x higher in countries where little meat is eaten
Q: What is the normal total body iron content?
-2+ grams in females, 2-6 grams in males
Q: What percent of the iron ingested is functional?
-80% of iron is functional, hemoglobin contains about 70% of body iron, iron also found in myoglobin, and iron containing enzymes (e.g., catalase and cytochromes), 15% - 20% is storage iron (hemosiderin, ferritin)
-1 gram of hemoglobin contains about 3.4 mg of iron
Q: What is the average intake and loss of iron daily?
-intake about 10-15 mg/day, about 10% of which is absorbed (mostly in duodenum, some in jejunum
-males/non-menstruating females lose approx. 1 mg/day, menstruating females lose about approx. 2 mg/day (40-60 mL during normal period)
Q: What happens with iron loss INC?
-if lose > 80 mL/period then you eventually develop iron deficiency
Q: What does transferrin do?
-is an iron binding protein (beta-globulin) that transports iron in plasma, responsible for delivering iron to immature erythroid cells
Q: What are hemosiderin granules?
-aggregate masses of iron stored in cells
-hemosiderosis- innocuous excess iron accumulation in organs, e.g., the liver and spleen
Q: What does ferritin do?
-a protein and iron complex (apoferritin is the protein portion) found in many tissues, is the major tissue protein for iron stores, minute amounts of ferritin are normally found in plasma
-serum levels are a good indicator of body iron stores (exceptions - not reliable in patients with liver disease, inflammatory states, (infections and non-infections) and malignancies)
Q: What are the levels of ferritin that lead to diagnosing iron deficiency or overload?
-iron deficiency - serum ferritin is < 12 g/liter
-iron overload - values of 5,000 g/liter are possible
-each microg/liter of ferritin in plasma indicates about 10 mg of stored iron
Q: What are the three pools of iron compartments in the body?
-metabolic, storage and transit pool
Q: Describe the metabolic pool of iron.
-include iron hemoglobin, myoglobin, electron transport chain, proteins, and enzymes, most metabolic iron regenerated through RBC turnover
Q: Describe the storage pool of iron.
-major stores are found in hepatocytes and macrophages, iron is found complexed to apoferritin (a 450 - kDa protein that binds up to 4,500 iron atoms)
-body stores vary from children, males and females
-children and adolescence need iron for growth and storage is virtually absent
-adult males have iron stores that INC slowly (elderly is borderline toxic)
-women have minimal stores during child-bearing years (post-menopausal INC to parallel those of men)
Q: Describe the transit pool of iron.
-includes transferrin
-transferrin has two iron-binding sites, is a 80 kDa protein, turns over iron approx. 10 times/day, and iron delivery is mediated by transferring receptor
Q: Describe the mechanism of iron uptake by a cell.
-there are transferrin receptors (TfR) on cell surface that is necessary for iron uptake, TfR binds plasma transferrin with preference for diferric transferrin
-the TfR-transferrin complex is internalized via endocytosis, endosome has lower pH which causes detachment of iron, iron escapes into cytosol and TfR-transferrin complex recycles to cell surface (apo-transferrin is released and another diferric transferrin binds)
Q: What does the uptake of iron by the cell depend on?
1) concentration and percent saturation of transferrin
2) number of TfR’s on cell surface
Q: Describe the mechanism of ferritin and TfR production.
-is depedent on iron in cytosol
-involves specific mRNA sequences (Iron - Responsive Element = IRE) that binds to Iron Binding Protein (IBP) which has a greater affinity for IBP in absence of iron
-ferritin production: IBP binds to IRE of ferritin mRNA and inhibits translation, thus, when cellular iron concentration is low, more IBP binds and suppresses ferritin production
-TfR production: IBP binds to IRE of TfR mRNA which leads to stabilization of mRNA, thus, low cellular iron concentration leads to increased TfR production
Q: Describe the levels of serum iron.
-may be decreased in severe chronic disease states (e.g., malignancy, uremia, cirrhosis and chronic infection)
-usually higher in morning, subject to considerable diurnal variation
Q: What are the normal serum iron levels?
- in men: 120 microg/dl
-women: 100 microg/dl
-normal individuals have transferrin that is about one-third saturated with iron
Q: What is total iron binding capacity of serum?
-approximately 300-350 microg/dl (frequently decreased with chronic illnesses and infections, neoplasms and arthritis)
Q: What are some differential diagnoses for hypochromic anemias?
1. Iron deficiency (DEC serum iron, DEC serum ferritin, and INC TIBC)
2. Anemia of Chronic disease (DEC serum iron, normal serum ferritin, DEC TIBC)
3. Thalassemia (normal serum iron, normal serum ferritin, normal TIBC)
Q: Why is iron low during an infection or chronic disease?
-when have a infection or chronic disease, want iron low because infection needs iron to survive, want low free iron and don’t want iron to be transported (DEC serum iron and TIBC)
Q: What are some causes of iron deficiency?
-low dietary intake (common in infants, greatest need in first year of life, premature baby deprived of 3-4 mg/day, INC incidence in infants consuming only cow’s milk)
-poor absorption (after gastrectomy or in patient with malabsorption disease, prolonged achlorhydria, surgery, etc.)
-excessive demand (pregnancy)
-chronic blood loss (the most common cause of iron deficiency in the western world, e.g., peptic ulcer disease, carcinoma, hemorrhoids, menses, hemosiderinuria, hemoglobinuria, etc.)
Q: What are the characteristics of hypochromia in iron deficiency anemia?
-significant hypochromia does not ordinarily develop until the bone marrow iron stores are depleted, early-on the anemia may be normochromic and normocytic, pass through a dimorphic phase of two RBC populations
Q: What happens to leukocytes during iron-deficiency anemia?
-WBCs and platelts in peripheral blood are not affected
-thrombocytosis often occurs
-retic count may be normal but usually DEC
Q: Describe the morphology of the bone marrow in a patient with iron-deficiency anemia?
-scanty, frayed, cytoplasm in later stage normoblasts w/ absent iron stores in bone marrow (Prussian Blue stain)
Q: With low levels of iron in iron-deficiency anemia, what can a depletion in iron containing enzymes cause?
-alopecia, koilonychias (spoon-shaped nails that are thin and ragged), atrophic glossitis, atrophy of gastric mucosa, malabsorption problems and pica
Q: What happens to the blood indices in iron-deficient anemic patients?
-MCV, MCH and MCHC may all be decreased by the time anemia appears, but not always
-MCV (45-67% of patients), MCH (80% of patients) and MCHC (20-80% of patients)
Q: From a nutritional standpoint discuss the relevance of iron in anemia.
-most diets in western world have adequate amounts. Exception = infants have increased requirements, especially from 3-4 months of age.
-considerable iron can come from cooking in iron pots
Q: What is hemochromatosis?
-iron overload syndrome with associated parenchymal cell damage (Prussian blue stain)
Q: What foods are high and low in iron?
-high in muscle, liver, soybeans, low in eggs, leafy vegetables, fish
Q: What may cause Pearl-iron deficiency anemia?
-Pearl - Iron deficiency anemia of unknown etiology in adult males or postmenopausal women (in the western world) should be considered to be caused by GI blood loss until proven otherwise!
Q: What are the sequence of events that leads to the development of iron-deficiency anemia?
1. iron depletion stage (iron is mobilized from stores, storage iron DEC, plasma ferritin DEC and plasma IBC (transferrin) INC
2. iron deficient erythropoiesis (when iron stores are depleted, plasma iron levels fall, saturation of transferrin falls below 15%, free red cell protoporphyrin INC and % of sideroblasts DEC in bone marrow)
3. iron deficiency anemia stage (anemia becomes detectable, gradually becomes microcytic, finally both microcytic and hypochromic)
4. anemia does not develop until bone marrow Fe stores are depleted (wehre they become microcytic and hypochromic-last thing we see)
Q: What is the treatment plan for iron deficiency?
-oral or parenteral (size of tablets is a compromise between what is needed and tolerated (about 1 in 10 get significant gastric or intestinal irritation))
-satisfactory response to oral medication - increase of 2 grams of hemoglobin after a 3 week trial
-6 months of oral medication are usually required to correct the anemia and replenish the iron stores
Q: In iron-deficient anemia, how are the RBCs classified?
-microcytic, hypochromic
Q: What are the components of the iron panel?
-serum iron, TIBC, serum ferratin and transferrin saturation
Q: How will the iron panel appear in patients with iron-deficiency anemia?
-DEC serum iron, INC TIBC, DEC serum ferratin, DEC transferrin saturation
Q: Why is TIBC INC in anemia?
-TIBC is a true measure of serum transferrin, which is elevated in these patients because liver makes more of transferrin to try to pick up more iron
Q: What does serum ferritin measure?
-is a measure of iron stores in the tissues because there is a certain percentage of iron that leaks out of these patients each day, proportional to amount of iron in tissues. Pick this test if can only pick one. Serum ferritin is affected by infections, inflammation, and neoplastic disease, so can lead to inaccuracies, these will lead to elevated serum ferratin levels.
Q: Why is serum ferittin level normal in some patients with anemia?
-If someone with anemia is not showing the microcytic, hypochromic, their serum ferratin may be elevated enough that it is up to the normal range (due to fever), but they are still anemic, so be careful.
Q: In what form of Fe is iron absorbed?
-iron is absorbed in the ferrous (2+) state
Q: What is atrophic gastris?
-pt produces no acid due to destruction of parietal cells, become iron deficient, because iron can’t be made in the reduced state so there is no iron absorption
Q: What is the differential diagnosis for microcytic, hypochromic anemia?
-think of 2 diseases, iron deficiency or thalassemia
Q: How can iron deficiency and thalassamia be differentiated from each other?
-These can be differentiated through an iron panel (which is for iron deficient people) and see serum ferritin test, RDW is also elevated in iron deficiency but normal in thalassemia (problem in Hb synthesis)
-Patients that have thalassemias have other ways to diagnose (say through Hb electrophoresis)
-In Iron deficiency, most patients will come in with normachromic normacytic pattern, only when they are depleted of iron, will they show hypochromic and microcytic pattern.
Q: What stain is used to measure iron?
-Prussian blue, all blue deposits is where iron is
Q: What are some characteristics associated with iron overload?
-hemachromatosis, hemosiderosis, see lots of blue
Q: What are some characteristics associated with iron deficiency?
-there are no blue residues, microcytic and hypochromic
Q: When analyzing anemia, what are the steps involved in classifying the anemia?
-First must look at red cell morphology, hct and Hb, then can classify what type of anemia patient has based on the morphology of the red cells
-Then look at MCV and MCHC: size of red cell and amount of Hb in them
-RDW will give anisocytosis or not
-Finally look at platelets (normal is 150,000 – 400,000), Iron deficiency pts usually have thrombocytosis (increase in platelets). This is an indicator of iron deficiency because patients with thalassemia do not have thrombocytosis.
Q: What should be done if someone is suspected of being iron deficient but cannot afford iron panel?
-look at conjunctiva mucous membrane (sclera of eye), most people look pale, give a blous of iron and check on her in a week, to see if she’s made progress, do H&H, retic count (to see if bone marrow is responding)
Q: What is the pathophysiology of megaloblastic anemia?
-anemia of ineffective erythropoiesis with impaired DNA synthesis, have bone marrow erythroid hyperplasia and a DEC retic count
-red cells are macrocytic, increased N/C ratio, prone to intramedullary hemolysis (elevated indirect bilirubin (ineffective erythropoiesis) and elevated LDH)
Q: What are the main causes of megaloblastic anemia?
-B12 deficiency or folic acid deficiency
-both are coenzymes in the pathway for DNA synthesis, deficiencies of either result in deranged or inadequate DNA synthesis, synthesis of RNA is unaffected therefore, cytoplasm develops normally
Q: Describe the morphology of peripheral blood in megaloblastic anemia.
-peripheral blood RBCs are normochromic, have marked anisocytosis and poikilocytosis (with MCV > 1003), and many macro-ovalocytes
-decreased reticulocyte count
-with severe disease nucleated RBCs appear
-neutrophils are large (macropolys), some are hypersegmented, often mild neutropenia
-thrombocytopenia common
Q: Describe the bone marrow morphology in megaloblastic anemia.
-usually hypercellular
-megaloblastic changes include (1) nuclear-cytoplasmic asynchronism or dissociation, (2) nucleus remains large and relatively immature, and (3) cytoplasm matures at normal rate
-granulocytes have (1) nuclear asynchrony, (2) “giant” metamyelocytes and band forms, and (3) hypersegmented PMNs
-megakaryocytes may be large or multi-lobulated
-M/E ratio is flattened or even reversed
Q: What are some causes of vitamin B12 deficiency?
-decreased intake due to (1) poor diet (rare) or (2) impaired absorption due to (intrinsic factor deficiency, pernicious anemia, total gastrectomy, malabsorption states (tropical and nontropical sprue), diffuse intestinal disease (regional ileitis), malignancies, e.g. lymphomas, fish tapeworm (Diphyllabothrium latum), chronic pancreatic disease, bacterial overgrowth
-increased demand due to (1) disseminated CA or (2) pregnancy
Q: What are some causes of folic acid deficiency?
-inadequate intake due to (1) inadequate diet – alcoholism, (2) impaired absorption – malabsorption, or (3) overcooking vegetables
-increased requirement due to (1) pregnancy, (2) infancy, or (3) markedly increased hematopoiesis
-impaired utilization due to folic acid antagonists (e.g. methotrexate)
Q: What diseases occur when a patient is unresponsibe to B12 or folic acid?
-unexplained disorders-pyridoxine-responsive megaloblastic anemia
-neoplastic (erythema myelosis)
Q: Describe some general information concerning pernicious anemia.
-due to chronic atrophic gastritis with failure of intrinsic factor production
-juvenile PA, not well understood, similar to adult form but onset in 20’s
Q: Describe vitamin B12?
-contains cobalt atom and a corrin ring (similar to porphyrin ring), cannot be synthesized in human body
Q: What are the diet and requirements for vitamin B12?
-normal diets contain large amounts, only 2-3 ug required per day, total body pool is ordinarily 2-5 mg and several years are required to deplete normal reserves
Q: What is transcobalamin II?
-it is a plasma transport protein that delivers vitamin B12 to liver and other cells of body
Q: What two reactions in man are known to need vitamin B12?
-cofactor in conversion of homocysteine to methionine
-formation of succinyl coenzyme A
Q: Describe intrinsic factor (IF) and what it does?
-secreted by parietal cells in fundus of stomach (along with HCl)
-combines with ingested B12 to form a stable complex (which resists peptic digestion)
-mechanism of absorption (in ileum) is still unknown
Q: Describe the epidemiology of pernicious anemia.
-more common in Scandinavian, English and Irish descent (up to 0.2% of this population), slightly more common in males, more common after age 50
Q: Describe the pathophysiology of congenital pernicious anemia.
-is autosomal recessive
-total absence of intrinsic factor (IF) and normal secretion of other gastric juices, there are no antibodies to IF or parietal cells
Q: Describe the pathophysiology of the immunologic (autoimmune) form of pernicious anemia.
-there antibodies to parietal cells and IF
-cell mediated immunity is activated and include (1) lymphocytotoxic antibodies in one-third of patients, (2) CD4/CD8 ratio increased, and/or (3) Ts cells decreased
-chronic atrophic gastritis
Q: What is the clinical manifestation of pernicious anemia?
-insidious onset
-anemia and related symptoms including weakness, fatigue, and lightheadedness, severe anemia can lead to congestive heart failure
-type of hemolytic anemia (ineffective erythropoiesis) can lead to jaundice
-complaints of loss of appetite are common
-glossitis (50%)
-neurologic manifestations (subacute combined degeneration of spinal cord)
Q: Describe the neurologicals manifestations associated with pernicious anemia.
-degeneration involving the posterior and lateral columns of the spinal cord
Q: What are the laboratory findings associated with pernicious anemia?
-CBC-anemia with elevated MCV and macrocytes and hypersegmented PMN’s
-serum Vitamin B12 levels
-10-50% of patients exhibit iron deficiency anemia
-bone marrow
Q: What Abs are synthesized in gastric mucosa in patients with pernicious anemia?
-Blocking antibody - blocks B12-IF binding (75% of patients)
-Binding antibody – interferes with B12-IF complex binding to ileal receptor (50% of patient
-Parietal canalicular antibody - less specific - found in 85-90%, but also in 50% of patients with atrophic gastritis not associated with pernicious anemia
Q: What is the Schilling Test?
-measures amount of radioactive B12 in a 24 hour urine (definite test)
-procedure:
(1) orally - give a small dose of radioactive B12
(2) two hours later, inject a large “flushing” dose of nonradioactive B12
(3) normal individuals will excrete  7% or more of the radioactive dose in the urine in 24 hours (patients lacking intrinsic factor do not absorb the B12 well and excrete < 7%)
-it is necessary to REPEAT the test giving intrinsic factor (porcine) orally along with the small dose of radioactive B12, if the patient has PA (and, therefore, lacks intrinsic factor) the result will be normal on the repeat test)
-if results are still abnormal, some other cause for the malabsorption must be sought, e.g., sprue, etc
Q: What does the validity of the test results show?
-validity of test result depends on good renal function and proper collection
Q: What is the treatment for PA?
-parenteral vitamin B12 q 1-3 months
Q: What is the function of folic acid?
-acts as an intermediary in transfer of one-carbon atom unit (formyl or methyl groups)
-needed for DNA synthesis
-plentiful in raw foods (eggs, milk, leafy vegetables), destroyed by cooking
-common type of deficiency
Q: What are the major causes of deficiency?
-decreased intake due to inadequate diet (alcoholics, indigents and elderly), is the most common cause
-decreased absorption (sprue, intestinal lymphoma)
-increased requirement (pregnancy, infancy, metastatic carcinoma)
-impaired utilization - particularly from antimetabolites used in cancer chemotherapy <methotrexate is a folate antagonist>
-alcohol also blocks the delivery of liver folate stores to the bone marrow
Q: What is the clinical manifestations of folic acid deficiency?
-same as Vitamin B12 deficiency but lacks neurologic changes, although dementia and depression have been reported, there are neural tube defects in fetus as well
Q: What are the laboratory findings for folic acid deficiency?
-CBC shows anemia with high MCV and macrocytes and hypersegmented PMN’s
-folate levels, use red cell to meausre (more stable
Q: What role does pernicious anemia have on vita B12 deficiency?
-PA can cause vita B12 deficiency, is autoimmune disease in which antibodies are formed against parietal cells so cannot make intrinsic factor (IF). IF comes from parietal cells of stomach along with HCl
Q: Describe immunofluroescent assay.
-can show the Ab bound to the parietal cell. Use an Ab bound to a fluorescent dye as a marker against human IgG
-Direct test: take a cell (biopsy material) and add the flor labeled anti-human IgG antibody. Wherever human cells have an antibody, the anti-IgG will bind and fluoresce -> one step -> looking for cells already coated with ab
-Indirect test: ANA (anti-nuclear-antibody), have a target cell, add patient’s serum to this and allow it to bind and then add the flor labeled antibody -> looking for ab in patient’s serum
Q: Describe achlorhydria.
-not making HCl, person becomes iron deficient, this occurs in pernicious anemia because parietal cells are targeted
-This gives a MCV in normal range and RDW elevated -> have big and small cells, see macro, micro, and normacytic cells
Q: What are some other causes of vita B12 deficiency?
-rarely due to diet, GI diseases like Crohn’s disease (ileitis), diseases of small intestine and ileum, tapeworms, bacterial overgrowth (Whipple disease), pancreatic insufficiency, terminal ileum resection
Q: What role does pancreatic insufficiency have on vita B12 deficiency?
-Normally, when ingest food, salivary glands produce an R protein that binds to B12 to make it resistant to the acid in the stomach -> goes to the small intestine -> pancreatic enzymes break off the R protein so B12 can bind to intrinsic factor and get absorbed. Thus pancreatic insufficiency leads to nonabsorption of B12.
Q: What does B12 deficiency lead to?
-Big cells due to asynchronous growth, delay of DNA synthesis in nucleus of red cells and cytoplasm has RNA and ribosomes, growing at a normal rate. Nuclear growth slows down, cytoplasm is maturing faster, thus asynchrony -> results in cells getting bigger, waiting for nucleus to mature
Q: In B12 deficiency, what does the bone marrow aspiration show?
-In bone marrow aspiration, cell is in prorubriocyte stage, cytoplasm large and dark because making Hb, leads to asynchrous development
Q: What are the cell characteristics in B12 deficiency?
-Cells have pink cytoplasm, but a non-condensed nucleus -> so get macrocytosis
-Both RBC and WBC are large, ANY nucleated cell is larger than it should be
Q: Which is more common, folate or B12 deficiency and why?
-folate more common than B12 deficiency because the body stores for Vit B12 are such that it takes a year for you to become deficient, whereas stores for folate are less so can become deficient in a couple of months
-the most common macrocytic anemia is megaloblastic anemia due to folate deficiency
Q: Why are the cells in the bloodstream of patients with megaloblastic anemia macrocytic?
-Macrocytes in the blood stream due to asynchronous development of blood cells, nucleus grows slower than cytoplasm due to deficiency in Vit B12 and folate defect in DNA synthesis. Second symptom is homocyst levels increase.
Q: Why is homocysteinuria bad?
-have increase in homeocys which is a risk factor for venous thrombosis and cardiovascular disease in large quantities
Q: What is on the differential diagnosis with a patient who has macrocytic anemia?
-B12 deficiency
-Folate deficiency, pernicious anemia
-Liver disease: patients produce a lot of cholesterol that binds to RBCs making them bigger in appearance
-Reactive reticulocytosis (so many reticulocytes, shift cells), these can all show an increase in the MCV, appearing macrocytic, CBC comments will say presence of polychromatophilic cells (multiple colors)
Q: What should patients with macrocytic anemia be tested for?
-serum B12-Can be equivocal, so give patient B12 (viscous injection) and follow up in 7-10 days, then perform H&H or retic count (but only if there was a previous baseline). If H&H goes up, probably had B12 deficiency, but can’t be completely sure, will have to run a Schilling test to make sure and see where the problem actually was (IF, pancreatic, etc).
-serum folate- Since it is the most common cause, run this one first (Serum folate levels change more than RBC folate level, i.e. eating salad before test, so not correlated with the blood, best to do both RBC and serum folate levels)
Q: What is methyl-THF and methyl-THF trap?
-5-methyl-THF is made from serine and glycine by removing a methyl group, there can be a m-THF trap in which m-THF accumulates. Dimethyl THF leads to falsely elevated folate in the serum.
Q: What can cause methyl-THF trap?
-In reaction of homocysteine -> methionine, 5-methyl THF donates a methyl group, B12 is required. Without B12, get an accumulation of homocyteine AND methyl-THF trap! (Also involved in succinyl CoA)
Q: How does methylTHF trap show up in laboratory tests?
-Low red cell folate and elevated serum folate indicates methylTHF trap
Q: What is the difference between folate deficiency anemia and B12 deficiency anemia?
-Only difference between this and B12/pernicious anemia is that if it becomes severe enough, B12 can lead to neurological problems, resulting in demyelination of the posterior/lateral columns, get tingling/numbness of the extremities, psych problems, etc.
-make sure diagnosis for folate def. is really folate def. and not B12, because can lead to neurological damage
Q: If someone is diagnosed with B12 deficiency, and three months later they come back and look at the smear and they have macrocytes again, showing macrocytic anemia. Why does this occur?
-This occurs because when turn the red cells on, they go at max and use all the folate, so pt must supplement the folate from diet, or they may become deficient again, this occurs in someone who was treated for B12 deficiency. (RBC lifespan is 120 days.)
Q: What type of colon cancer is most responsible for blood loss?
-left sided colon cancer, napkin ring lesion, get stenosis of that lesion, right side is more hemorrhaging and blood loss, that is the tendency
Q: In what conditions is bone marrow non-functioning?
-myelofibrosis, myelometaplasia
-in this situations, you get INC CO, INC respiratory rate, INC erythroipoietin
-leads to extramedullary hematopoeisis (spleen and liver) and eventually splenomegaly and hepatomealy
Q: Why would end-stage renal function lead to anemia?
-DEC erythropoietin production
Q: Why are child-bearing age women susceptible to iron deficiency anemia?
-if they have prolonged menstrual cycles, can become iron deficient if lose enough blood (the population is most iron deficienct-women in there 20s or 30s)
Q: Why do long-distant runners have iron deficiency problems?
-have a tendency to hemorrhage because of length of exercise and distance of exercise (due to pounding of trauma)
Q: In patients with iron deficiency, what is the order of things seen during examination?
-DEC in serum iron, then DEC serum ferritin and then change morphology (hypochromic, microcytic)
Q: What are the components fo the iron panel?
-serum iron, serum ferritin, TIBC and % saturation
-serum ferritin is the best test (if only order one, then this is the one to order), levels of serum ferritin mimic the amount of iron being stored
-if serum ferritin is normal, then iron stores are normal, then not iron deficient, can therefore be anemia of chronic disease, iron is sequestered by macrophages and does not get into mature RBCs, there serum ferritin tends to be in the normal range, have DEC amounts of transferrin
Q: Describe hemachromatosis.
-will get into more detail
-condition inherited or acquired, absorb more iron (maybe 10-20X) than normal, body doesn’t get rid of iron very well, body hangs onto iron very easily
-macrophages take up iron and store it
-over a long period of time the amount of iron that is around will surpass the engulfing capacity of the macrophage and is now stored in parenchymal cells, can’t package it so try to start to metabolize it making free radicals killing the cells
-over time, if sufficient cells are dead that portion of the organ dies (liver, pancrease, heart)
Q: Describe the absorption of iron and its maintenance in reduced form.
-in GI tract as ferrous 2+ form, in order to keep Fe in the 2+ state, need an acidic environment (like stomach and HCl from parietal cells)
-in pernicious anemia, there is no HCl (destruction of parietal cells) so there is an iron deficiency (as well as a B12 deficiency)
Q: What is the differential for patients with microcytic, hypochromic anemia?
-iron deficiency, thalasseia, lead poisoning, anemia of chronic disease, sideroblastic anemia
Q: How is the iron difficiency differentiated from the differential for microcytic, hypochromic anemia
-thromobocytosis in patients who have iron deficiency
-also have pica (appetite for food without nutritional value, dirt)
Q: What conditions can cause an elevation in serum ferritin?
-inflammation, infection and malignancies, considered by soma positive acute phase protein
Q: What is a positive acute phase protein?
-an example would be C-reactive protein (CRP)
-a non-specific indiator of inflammation and infection (are elevated in instances of inflammation and infection)
-CRP hangs around until the cause of the response is accurately treated
-serrum ferritin is also considered an acute phase protein so may go up with inflammation and infection (don’t waste your time running a serum ferritin with someone who has pneumonia)
Q: Why does chronic pancreatitis cause B12 deficiency?
-can’t release R factor because don’t secrete pancreatic enzymes
Q: Why does B12 deficiency lead to macrocytic cells?
-B12 is needed for the synthesis of thymidine, have problems with DNA synthesis but not protein, so nucleus is smaller than cytoplasm
Q: How does B12 deficiency lead to neurological problems?
-need B12 for methyl-malonyl -> succinyl CoA, end result is abnormal lipid metabolism and formation and demyelination of spinal tract (particularly the lateral tracts)
Q: what happens with LDH in hemolytic anemia?
-elevated LDH 1 and depression in 2 (1, 2 LDH flip), never run LDH on hemolyze serum because get 1,2 LDH flip
Q: Describe haptoglobin.
-protein that binds to free Hb, free Hb is toxic to cells in the kidney, produced by the liver, haptoglobin-Hb complex is taken back to liver
-individuals with hemolytic anemia have a DEC in haptoglobin, but INC in haptoglobin-Hb test
Q: What is the iron distribution in the normal body?
-approximately 80% of the functional iron is founding hemoglobin, myoglbin and iron-containing enzymes such as catalase and the cytochromes contain the rest
-the storage pool represented by hemosiderin and ferritin contains approx. 15% to 20% of the total body iron
Q: Where in the body is ferritn located?
-ferritin is found in all tissues but particularly in liver, spleen, bone marrow and skeletal muscles
-in the liver most ferritin is stored within the parenchymal cells, in other tissues it is mainly in the mononuclear phagocytic cells
Q: Describe the binding capacity of transferrin.
-synthesized in the liver
-about 33% saturated with iron, yielding serum iron levels that average 120 ug/dL and 100 ug/dL in women, so TIBC is 300-350 ug/dL
Q: How does chronic blood loss lead to iron deficiency anemia?
-most common cause of iron deficiency in the Western world, if bleeding occurs into tissues or cavities of the body, the heme iron can be totally recovered and recycled
-external hemorrhage as from GI tract (due to peptic ulcers, hemorrhagic gastritis, gastric carcinoma, colonic carcinoma, hemorrhoids), urinary tract (renal, pelvic or bladder turmors) or genital tract (menorrhagia, uterine cancer) deplete iron reserves
Q: Describe anemia of chronic disease.
-impaired red cell production associated with chronic diseases, most common cause of anemia among hospitalized patients in the US
-assocaited with reduced erythroid proliferation and impaired iron utilization so mimics iron deficiency
Q: What are the common features characterzing anemia of chronic disease?
-low serum iron and reduced total iron-binding capacity in association with abundant stored iron in the mononuclear phagocytic cells
Q: Describe the pathophysiology of anemia of chronic disease.
-erythropoietin levels are low due to generation of IL-1, TNF and interferon-gamma, these are made by the underlying chronic inflammatory or neoplastic disease
-these cytokines also release hepcidin which inhibits the release of iron from the storage pool
Q: Why is vitamin B12 and folic acid important for the body?
-they are coenzymes required for synthesis of thymidine, a deficiency results in defective nuclear maturation due to deranged or inadequate DNA synthesis with an attendant delay or block in cell division
-does not affect RNA and protein synthesis so cytoplasmic maturation proceeds in advance of nuclear maturation (nuclear/cytoplasmic asynchrony)
Q: Describe the steps involved in the absorption of vitamin B12.
-free B12 in the stomach binds to R-binders, in the duodenum, R-B12 complexes are broken down by the action of pancreatic proteases and release B12 with can then associate with intrinsic factor (which was made in the stomach by parietal cells
-IF-B12 is transported to the ileum where it is endocytosed, B12 then binds to transcobalamin II (carrier protein) that delivers B12 to liver and other cells
Q: What lab criteria are needed for diagnosing iron deficiency erythropoiesis?
1. DEC serum iron
2. normal to INC TIBC
3. DEC serum ferritin
4. DEC transferrin saturation
5. INC free RBC protoporphyrin