內(nèi)容教程22貧血kev

1、Nutritional AnemiasJeffrey J. Pu, MD, Ph.D., November 17, 2015 no conflicts to disclose mended Readings“Orange book, 2nd edition” p 120-122DiPiro et al. Pharmacotherapy: A Pathophysiologic Approach, chapter entitled “Anemias”O(jiān)bjectivesDescribe features and pharmacologic manag

2、ement of the 3 most common nutritional anemias, including correction by nutritional and pharmacologic means Identify the correct dietary supplement for a given set of lab valuesDescribe the role and risks of erythropoietins as pharmacologic agentsApply the pharmacologic principles discussed to a giv

3、en clinical caseTerminologyHemoglobin (ug/dL)Amount of hemoglobin per volume of whole bloodProvides a rough estimate of the oxygen-carrying capacity of bloodIf reduced, may be due to (a) a decrease in total RBCs (made or lost) or (b) less Hgb being carried per RBCHematocrit (Hct) (%)Volume of RBCs p

4、er unit volumeRoughly 3 times the hemoglobin value Alterations may occur with abnormal cell shape or size; reduction in RBC number; increased plasma volume RBC (million/mm3) number of RBCs per unit of bloodReticulocytes 0.5-1.5% of erythrocytes MCV (mean corpuscular volume) (fL)Hct RBCIf larger than

5、 normal = macrocytic anemiaIf less than normal = microcytic anemiaTerminology, continuedTransferrin transport protein that carries iron to bone marrowTIBC (total iron binding capacity) Iron deficiency anemia is characterized by a high TIBCFerritin the storage form of ironWhen low, indicative of iron

6、 deficiency anemia Serum iron (ug/dL) FolateVitamin B12Case one “Ive been feeling terrible for a while and I cant remember anything.” A 74 year old male presents to the Veterans Affairs Medical Center for a routine check-up. He has been feeling weak and lightheaded. He complains of being clumsy and

7、having a feeling of pins and needles in his feet and hands. Meds: omeprazole, glipizide, metformin, pravastatin, quinapril, pseudoephedrine, warfarin.CBC Results Hgb 11.3 g/dL (13.5-17.5)Hct 33.5% (41-53)MCV 98 um3 (80-100)Iron 85 mcg/dL (50-160)Folate 2.2 ng/mL (1.8-16)B12 97 pg/mL (100-900)Signs a

8、nd Symptoms of B12 deficiencyLaboratory:Macrocytic RBCsMCV may be elevatedDecreased vitamin B12Symptoms: triad- weakness, sore tongue, paraesthesiasOther symptoms: nausea, anorexia, ataxia, dementia, personality changes, impaired memory, weakness, loss of dexterityB12Naturally-occurring B12 comes in

9、 a variety of formsFound only in tissues of animals that have obtained the vitamin from synthesis by their intestinal flora and in foods that have been fermented by B12-producing bacteriaLiver is the richest sourceMuscle meats, eggs, fish, milk, yogurt; fortified breakfast cereals are also good sour

10、cesB12Vitamin B12 (cobalamin)Essential for many cellular functionsFolic acid metabolismNecessary for conversion to tetrahydrofolateB12 deficiency can cause a secondary folate deficiency by folate “trapping”Fat and carbohydrate metabolismConversion of Methyl Malonyl CoA to Succinyl CoA Protein synthe

11、sisConversion homocysteine into methionineDNA synthesisThymidylate synthesis is impaired with UTP accumulating and mis-incorporated into DNACell replication B12 deficiency causes failure of cell division in all replicating cells, (i.e., most apparent in hematopoietic and mucosal cells)Faulty cell di

12、vision and impaired cell maturation defects lead to megaloblastic cellsVitamin B12 (cobalamin)Adequate B12 Depends Upon:Dietary intakeAcid-pepsin liberating B12 from dietary proteinsPancreatic proteases Parietal cell secretion of intrinsic factor (IF)Cobalamin-IF receptors in ileumCauses of B12 Defi

13、ciencyInadequate intake strict vegetarians Foods of animal origin are primary dietary source (meat, eggs, fish, milk)Average diet contains 5-30 mcg/day. The RDA is 2 mcg/day.Gastric or Small Bowel Disease removal of bowel, gastric body atrophy, lack of intrinsic factorDrugs that interfere with B12 a

14、bsorption/utilization: examples: metformin, colchicine, prolonged use of antacid therapyIdentifying B12 DeficiencyRegular screenings important for those over 50 yearsSerum B12 levelsNormal 150-750 pg/mlElevated methyl malonyl CoA (MMA) levelsElevated homocysteine levelsLow hematocritMCV 100 fLOval m

15、acrocytesAnti-IF antibodiesAnti-parietal cell antibodiesSchilling TestTreating B12 Deficiencies: Cyanocobalamin, HydroxycobalaminIM B12 replacement (1 mg)Daily for 3-7 daysWeekly for 4 weeksMonthly for lifeOral B12 replacement (1-2 mg daily)For those with increased requirements/nutritional deficiti.

16、e., Pregnancy, thyrotoxicosis, hemorrhage, malignancy, renal/liver disease Colchicine, metforminIntranasal Gel/Spray (Nasocobal)Side effects of B12 TherapyHypokalemiaHyperuricemiaRebound thrombocytosisSodium retentionAssessing ResponseImproved strength, well-being, might be evident within 24 hoursRe

17、ticulocytosis is evident in 2-5 daysHemoglobin rises in 1 weekMMA and homocysteine levels begin to decrease in 1-2 weeksNeuropsychiatric issues may require 6 months or longer of treatmentCase one “Ive been feeling terrible for a while and I cant remember anything.” A 74 year old male presents to the

18、 Veterans Affairs Medical Center for a routine check-up. He has been feeling weak and lightheaded. He complains of being clumsy and having a feeling of pins and needles in his feet and hands. Meds: omeprazole, glipizide, metformin, pravastatin, quinapril, pseudoephedrine, warfarin.Case Two“I have be

19、en irritable, tired, and restless lately”. KJ is a 73 yo man with a long history of bipolar disorder. He states he has been waking up frequently at night. He has had visual hallucinations and a racing heart. He drinks a six-pack of beer every evening. Meds: HCTZ, loratadine, docusate, tamsulosin, di

20、valproex, cholestyramine.CBC results Hgb 12.8 g/dL (13.5-17.5)Hct 38.4% (41-53)MCV 102.4um3 (80-100)Iron 67 mcg/dL (50-160)Folate 0.8 ng/mL (1.8-16)B12 331 pg/mL (100-900)Signs and Symptoms of Folate DeficiencyMCV100 fLMacrocytosisLow serum folic acidSymptomsPaleFatiguedTachycardiaMuscle weaknessIrr

21、itableRestlessDepressedDementiaFolic AcidAdult daily requirements: 200-400 ug/dayFolate stores in body (5 mg) are low and depleted in a few months with no dietary intake1999 all North American flour & cereal grains began to be supplemented Folate deficiency has fallen to 10%)Black or Dark stoolsCons

22、tipationHeart burn/stomach upset/cramping or pain, GI irritation, NauseaManaging OverdoseIpecac GI lavageSystemic chelation with deferoxamineResponse to TherapyReticulocytosis in 3-10 daysRise in Hgb within 2-3 weeksWhos most at risk for IDA?Premature infantsPregnant/lactating womenAdolescents durin

23、g growth spurtsAdults with slow GI bleedsPost gastric bypass surgery Case threeA 47 yo WF presents with complaints of “belly pain and tiredness all the time”. She had been taking Aleve 1 tablet twice daily for 7 months for knee osteoarthritis. Because of increasing pain, she increased the dose to 2 tablets three times daily about 2 months ago and added acetaminophen. Four years ago, she was diagnosed with PUD and she has been taking Ra