Anemia

Muhammad Dimas Y2008730091

Pembimbing : dr. Camelia Khairun Nissa Sp.PDStase Interna BLUD Sekarwangi Cibadak-Sukabumi

Definition of anemiaAnemia: A reduction in red cell mass O2-carrying capacity It is expressed in terms of reduction in the concentration of Hb (or RBC or Hct%) compared to values obtained from a reference population.(2 SD below normal)

Reference values (I) ParameterFemale MaleRBC (x1012/L)4.8+0.65.4+0.9Hb (g/dL)14+216+2Htc (%)42+547+5

Reference values (II)Ret (% / n)0.5-2.5 / 50-100x109/LMCV (fl)90+7MCH (pg)29+2MCHc (g/dL)34+2RDW (%)11.5-14.5

50 100200flRBC

%

ReticulocyteNormal RangesMale: % 0.8 - 2.5Female: % 0.8 - 4.1Corrected Rtc: Patient Hb/Normal Hb x Rtc %Reticulocytosis: > 100.000 /mm3

Definition of anemiaHb level of a patient which is below the normal ranges of that age and sex. For adults:WHO criteria define anemia as hemoglobin level lower than 12 g/dL in women and 13 g/dL in men But: The reference values for red cells ,Hb or Hct may difer according to sex/ageRaceAltitudeSocioeconomical changesStudy/reference etc

BEUTLER andWAALEN BLOOD, 1 MARCH 2006 VOLUME 107, NUMBER 5

WBC: x10E3/mm3 Hb:g/dLAge and blood count changes

ageWBCNeutrophylsEos.BasoLenfoMonoHb12 mo6-17.51.5-8.50.05-0.70-0.204-10.50.05-1.111.1-14.14 y5.5-151.5-8.50.02-0.650-0.202-80-0.811.2-14.36 y5-14.51.5-80-0.650-0.201.5-70-0.811.4-14.510 y4.5-131.8-80-0.600-0.201.5-6.50-0.811.8-1521 y4.5-111.8-7.70-0.450-0.201-4.80-0.8E: 16K: 14

!!!!!Plasma volume changes have to be considered before determining a diagnosis of anemia .Volume contraction:Underestimation of anemiaVolume overload: Underestimation of Hb level

Volume changes/acute bleeding and anemia normalHct (a/b%):NormalDehydration Hct:IncreasedAcute blood loss(early) Hct:unchangedChronic anemia Hct: Low12345Increased plasma volume Hct: Lowba

!!!!!A normal Hb in a patient in whom an elevated Hb level is expected may represent anemia .(eg:COPD + Hb:N)

!!!!!!Different red cell measures of the same patient may give discordant values in special conditions. (eg:Thalassemia trait)Eg: Low Hb, high RBC, low MCV Hb: 10 g/dL (anemia) RBC: 6.5 million/mm3 (erythrocytosis) MVC : 70 fL

!!!!Anemia is rarely a disease by itself,It is mostly a manifestation or consequence of an underlying (genetic or acquired) disease.The finding of anemia has to start attempts to disclose an underlying disease . What is the cause of anemia ?

Anemia leads to two symptom complexes;Tissue hypoxiaFatigue,dyspnea on exertion etcCompensatory attemptsTachycardia,hyperventilation etc

The amount of O2 necessary to support life is : 250 ml/min O2 carrying capacity of normal blood:1.34 ml/g-Hb (200 ml/L-blood)Cardiac output: 5000 ml/minO2 delivery to tissues : 1000 ml/min

Reduced levels of Hb results with reduced oxygen delivery to tissues , leading to tissue hypoxia.The symptoms and findings of anemia concern many different systems/organs due to the widespread nature of hypoxia.

The most pronounced effects and symptoms derive from skeletal muscles, heart,and central nervous system (due to their greater oxygen demand and compensatory actions).What is the mechanism underlying compensatory mechanisms ?

Hypoxia-Inducible Transcription Factor 1

A DNA binding proteinRegulated by the O2 tensionRegulates genes that promote cell survival under hypoxic conditionsUp-reg. EPO gene Up-reg.Glycolytic enzyme genesUp-reg. AngiogenesisRespiratory controlEnergy metabolism

EPO producing cellsHIF-1Muscle heart liver kidneyCarotid bodyGlomus cellsAll cells Vasc. endotheliumErythropoiesisAngiogenesis and vascular toneEnergy metabolismDecreased O2 consumptionIron metabolismRespirationEPO

Compensating mechanisms in anemia:The release of oxygen to the tissues is increased (reduced oxygen affinity of Hb)

Compensating mechanisms in anemia

The rate of blood circulation and cardiac output increases.An increase in plasma volume maintains total blood volume in normal or near normal ranges.Redistribution of blood flow.

Different patients may have different severity of symptoms even for the same level of Hb.The severity of the symptoms of anemia are related to;The severity of anemiaThe age,CVS,pulmonary status etc of the patientThe rate of the development of anemiaGradual orRapid onset

Clinical symptoms and findings of anemia (1)The symptoms and findings are related to anemia itself or to the underlying disease that causes anemia .The symptoms and findings related to anemia itself will be mentioned during this course.

Clinical symptoms and findings of anemia (2)Fatigue, weaknessTiredness, lassitude, reduced exercise tolerenceGeneralized muscular weaknessPallor /skin or mucous membranesSkin color may change due to other reasons;eg :Blood flow of skin, subcutaneous fluid , pigment changes

Pallor (paleness):Look atMucous membranes of mouth and pharynxConjunctivae,lips, nail beds,palmsCreases of the palms lose their pink colour when the Hb < 7g/dLIn pernicious anemia there is a lemon yellow pallor.Pallor + mild scleral icterus suggests hemolytic anemia.Pallor+ petechiae suggests severe bone marrow failure

Some other skin/mucosal changesPremature graying of hair:pern.anemiaHair loss and fragility + spooning of the nails:iron deficiencyChronic leg ulcers:Sickle cell or other hemolytic anemiaGlossitis/burning sense :Pern. anemia, iron deficiency(rare)Chelitis(angular stomatitis):iron def.Siideropenic dysphagia: iron def.Painful ulcerative mouth lesions: aplastic anemia/leukemia

Clinical symptoms and findings of anemia (3)Cardiovascular System(1)Palpitation and dyspnea (during activity)Angina pectorisClaudicatio intermittansMurmurs: Mid systolic (rarely diastolic) , mainly pulmonary valvular or apical or over major peripheral arteries or jugulary veins

Clinical symptoms and findings of anemia (3) Cardiovascular System(2)High output state: Collapsing pulse, high pulse pressureCardiomegalyCongestive failureIschemic ECG changes

Clinical symptoms and findings of anemia (4)Central nervous systemHeadacheFaintnessGiddinessTinnitusDecreased concentration abilityDrowsiness,decreased muscle strengthClouding of consciousnessSymptoms are more prominent in older patientsParesthesias:Vitamin B12 deficiency (or other).

Clinical symptoms and findings of anemia (5)Reproductive systemMenstrual changes:Amenorrhea ,Menorrhagia(mostly a cause of anemia)Loss of libido

Clinical symptoms and findings of anemia (6)Gastrointestinal system(these symptoms may indicate underlying disorder that might indeed be a cause of anemia)AnorexiaFlatulenceNauseaConstipation Weight loss

These should remind GIS disease as a cause of anemia (eg:a bleeding lesion-ulcer/malignancy etc)

Clinical symptoms and findings of anemia (7)Ocular Fundi:Pale and sometimesHemorrhagesPapillaedema

Clinical symptoms and findings of anemia (8)Renal Changes Slight proteinuriaConcentrating defectsFurther reduction of renal function in patients with previous renal impairment(Renal failure itself is a cause of anemia!!!!)Pyrexia: Due to a hypermetabolic state or other underlying disease (which may be a cause of anemia)

Some Other examples for history and physical examinationThe duration of symptoms (acute/insidious)Bleeding ? Nose/skin/urine/mens/stool etcFamily historyAnemia, gall stones and splenectomyBleeding disorderOccupation, hobbies,dietary history,alcohol or drug use,travel history etc (toxic/infectious contacts)Ask for skin and hair/nail changes

Some Other examples for history and physical examinationPain / mass / fever/systemic overview for an underlying diseaseRenal/endocrine/liver disease orChronic infection/malignancy/imflamatory conditionParasitisPregnanciesParesthesias ,walking difficultySternal or other bone tendernessSplenomegaly, hepatomegalyLymphadenomegaly

Diagnosis and investigation:Is the patient anemic?What is the type of anemia?What is the cause of anemia?

Classification of anemiaMorphologicNormocytic: MCV= 80-100fLMacrocytic: MCV > 100 fLMicrocytic : MCV < 80 fLPathogenic (underlying mechanism)Blood loss (bleeding)Decreased RBC productionIncreased RBC destruction/pooling

Normocytic AnemiasAcute post-hemorrhagic anemiaHemolytic anemia (except thalassemia and some other Hb disorders)Aplastic anemiaPure red cell aplasiaBone marrow infiltrationEndocrin diseasesRenal failureLiver diseaseChronic disease anemiaProtein malnutritionHypovitaminosis C

Microcytic anemiasIron deficiency anemiaThalassemiaSideroblastic anemiaLead poisoningAnemia of chronic diseases (some cases)

Macrocytic anemiasMegaloblastic

Non-megaloblastic

Megaloblastic Macrocytic AnemiasVit B12 deficiencyFolic acid deficiencyOther.

Non-megaloblastic Macrocytic AnemiasAnemia of acute bleedingHemolytic anemiasLeukemias (esp: acute)Myelodysplastic syndromesLiver disease

Aplastic anemiaDiseases infiltrative to the bone marrowAlcoholismHypothyroidismScurvy

Pathogenic classification(Causes of anemia)Relative (increased plasma volume)Decreased RBC productionBlood lossAnemia due to acute bleedingIncreased RBC destruction

Pathogenic classification (Causes of anemia)Decreased RBC productionDecreased Hb productionDefective DNA synthesisStem cell defectsPluripotent stem cellErythroid stem cell(progenitors)Other less defined reasonsBlood lossAnemia due to acute bleedingIncreased RBC destructionRelative(increased plasma volume)

Decreased Hb productionIron deficiency anemiaThalassemiaSideroblastic anemiaLead poisoning

Defective DNA synthesis

Vit B12 deficiencyFolic acid deficiencyOther.

Pluripotent stem cell defectsAplastic anemiaLeukemia or myelodysplastic syndromes

Defective erythroid stem cellPure red cell aplasiaAnemia of chronic renal failureEndocrin disease anemiaCongenital dyserythropoetic anemias

Decreased RBC production due to multipl or undefined mechanismsAnemia of chronic diseasesBone marrow infiltrationAnemia due to nutritional defects

Anemias caused by increased RBC destruction (hemolytic anemias) Can be classified as;Hemolysis due to intracorpuscular defectsHemolysis due to extracorpuscular defectsOrHereditary hemolytic diseasesAcquired hem. diseasesOrIntravascular hemolysisExtravascular hemolysis etc.

A Very Simple Classification of Hemolytic Anemias

Is the patient anemic ?RBC countHB levelHct levelVolume status

What is the type of anemia?History and physical exam.RBC,HB,Hct ,MCV, MCH,RDWRed cell morphology ( peripheral smear)Reticulocyte countIncresed ? Other Lab. investigations

Lab. investigation of anemia(1)

WBC count and differentialPlatelet count and morphologyESRBiochemistry, special tests and othersBone marrow exam.(only when indicated)

Lab. investigation of anemia(2)Serum values ofIronTIBCFerritinBilirubinsProteins / electrophoresisLDHVit B12 and /or Folic acid(None of these tests are routine screening tests)

Lab. Investigation of Anemia(3)Red cell enzymesHb F,A2,Hb electrophoresisCoombs testsLiver, renal, endocrin functional testsUrinalysisHemosiderinOccult GIS bleeding / parasites etc(tests should be chosen individually-do not order routinly )

Investigation of a microcytic hypochromic anemiaBlood FilmSerum IronSerum iron high Serum iron normal/high Serum iron low

Marrow for iron Hemoglobin studies Ferritin level Low Normal / High

Sideroblastic anemia Thalassemia ron deficiency Anemia of Abnormal Hb chronic disease

Investigation of a normocytic, normochromic anemia

Reticulocyte countRetic. normal / low Retic. high Bone marrow morphology hemolysis acute blood loss

NormalAbnormal Hypoplastic infiltration dysplastic Secondary anemia eg. Inflammation aplastic anemia leukemia myelodysplasia liver disease myelofibrosis Renal failure metastases endocrine failure

response to anemia treatment

Macrocytic anemia (MCV: high)

Blood filmReticulocyte count

Retic. HighRetic. Normal/lowBone marrow Non-megaloblasticMegaloblasticAcute blood loss orHemolytic anemianormoblasticdysplastic(MDS)folate or B12 levels(Other macrocytic anemias)folate Vit B12 deficiency deficiencyTreatment response

Daftar Pustakarepository.usu.ac.id/bitstream/123456789/21220/4/Chapter%20II.pdf(Universitas Sumatra Utara)www.kalbemed.com/.../04_194cme-pendekatan%20klinis%20dan%20di...pdf(IDI).

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