بسم الله الرحمن الرحیم. Аnemia – pathologic state,accompanied by decrease in...
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Transcript of بسم الله الرحمن الرحیم. Аnemia – pathologic state,accompanied by decrease in...
بسم الله الرحمن الرحیم
Аnemia – pathologic state,accompanied by decrease in the level of hemoglobin and the quantity of erythrocytes per unit of volume of the blood.
Erythrocytes - less informative index Erythrocytes - less informative index of anemia than the level of of anemia than the level of hemoglobin therefore, in the hemoglobin therefore, in the general practice the basic criterion general practice the basic criterion of severity is precisely Hb: of severity is precisely Hb:
Light degree of anemia - Hb 110-90 Light degree of anemia - Hb 110-90 g / l, g / l,
The average degree of severity - The average degree of severity - Hb 90-70 g / l, Hb 90-70 g / l,
Severe anemia - Hb below 70 g / Severe anemia - Hb below 70 g / literliter
Laboratory Definition of AnemiaLaboratory Definition of Anemia
Hgb:Hgb: Women: <12.0Women: <12.0 Men: < 13.5Men: < 13.5
Hct:Hct: Women: < 36Women: < 36 Men: <41Men: <41
RBC Life CycleRBC Life Cycle
In the bone marrow, erythropoietin enhances In the bone marrow, erythropoietin enhances the growth of differentiation of burst forming the growth of differentiation of burst forming units-erythroid (BFU-E) and colony forming units-erythroid (BFU-E) and colony forming units-erythroid (CFU-E) into reticulocytes.units-erythroid (CFU-E) into reticulocytes.
Reticulocyte spends three days maturing in Reticulocyte spends three days maturing in the marrow, and then one day maturing in the marrow, and then one day maturing in the peripheral blood.the peripheral blood.
A mature Red Blood Cell circulates in the A mature Red Blood Cell circulates in the peripheral blood for 100 to 120 days.peripheral blood for 100 to 120 days.
Under steady state conditions, the rate of Under steady state conditions, the rate of RBC production equals the rate of RBC loss.RBC production equals the rate of RBC loss.
Erythropoetin roleErythropoetin role
Classification of AnemiaClassification of Anemia I. Anemias resulting from acute blood loss I. Anemias resulting from acute blood loss II. Anemias resulting from a deficit of erythropoesis II. Anemias resulting from a deficit of erythropoesis
1) At the expense of maturation (mainly microcyte): 1) At the expense of maturation (mainly microcyte):
violation of absorption and utilization of iron (iron) violation of absorption and utilization of iron (iron)
violation of transportation of iron (atransferrinemia) violation of transportation of iron (atransferrinemia)
violation of recycling iron (thalassemia, violation of recycling iron (thalassemia, sideroblastic anemia ) sideroblastic anemia )
violation of reutilization of iron (anemia of chronic violation of reutilization of iron (anemia of chronic disease);disease);
AnemiaAnemia ( (continuedcontinued))
2) At the expense of differentiation 2) At the expense of differentiation (essentially normal): (essentially normal):
aplastic anemia (congenital and aplastic anemia (congenital and acquired) acquired)
3) At the expense of proliferation 3) At the expense of proliferation (mainly macrocytes) (mainly macrocytes)
B12-DEFICIENCY anemia B12-DEFICIENCY anemia
Folic-DEFICIENCY anemia.Folic-DEFICIENCY anemia.
AnemiaAnemia ( (continuedcontinued)) Anemias resulting from increased Anemias resulting from increased
destruction of erythroid series cells - destruction of erythroid series cells - haemolytic: haemolytic:
1) caused by internal defects of 1) caused by internal defects of erythrocytes erythrocytes membranopathy, enzimopathy, membranopathy, enzimopathy, haemoglobinopathies; haemoglobinopathies;
2) the external (extracllular) effects: 2) the external (extracllular) effects: autoimmune, traumatic, etc. autoimmune, traumatic, etc.
Classification D. Nathan, F. Oski, 2003, (book «Anemias Classification D. Nathan, F. Oski, 2003, (book «Anemias in children», NA Finogenova et al, 2004.): in children», NA Finogenova et al, 2004.):
The clinical value of bloodThe clinical value of blood
AutomaticAutomaticalal
CountingCounting
Units Units
Measure-Measure-mentment
Normal Normal LevelLevel
Short Short FormForm
HGB- Hemoglobin
G/Liter 120-160 HbHb
RBC - erythrocyte
1210 /L
3,9-5,9 ErEr
HCT -Hematocryte
%% 36,0-48,0 HtHt
MCV- average volume of erythrocyte
31 micron = 1 - femtoliter (fl)
80 - 9580 - 95
MCH – the average content of Hb in erythrocyte
Pikogram1 г =1012pikograms
27,0-31,02
Colour Index (0,85-1,0)
MCHC – average concentration of Hb in erythrocyte
G/dl или g %, less g/l
32,0-36,0
RDW – width of the distribution curve of erythrocyte by volume
%% 11,5-14,5 anisocytosis
Measurements of AnemiaMeasurements of Anemia HemoglobinHemoglobin = grams of hemoglobin per 100 = grams of hemoglobin per 100
mL of whole blood (g/dL)mL of whole blood (g/dL) HematocritHematocrit = percent of a sample of whole = percent of a sample of whole
blood occupied by intact red blood cellsblood occupied by intact red blood cells RBCRBC = millions of red blood cells per microL of = millions of red blood cells per microL of
whole bloodwhole blood MCVMCV = Mean corpuscular volume = Mean corpuscular volume
If > 100If > 100 → → Macrocytic anemiaMacrocytic anemia If 80 – 100 → If 80 – 100 → Normocytic anemiaNormocytic anemia If < 80If < 80 → → Microcytic anemiaMicrocytic anemia
RDW RDW = Red blood cell distribution width= Red blood cell distribution width = (Standard deviation of red cell = (Standard deviation of red cell
volume ÷ mean cell volume) × 100 volume ÷ mean cell volume) × 100 Normal value is 11-15%Normal value is 11-15% If elevated, suggests large variability in If elevated, suggests large variability in
sizes of RBCssizes of RBCs
Anemia due to Anemia due to Decreased Decreased Response to ErythropoietinResponse to Erythropoietin
Iron-DeficiencyIron-Deficiency Vitamin B12 DeficiencyVitamin B12 Deficiency Folate DeficiencyFolate Deficiency Anemia of Chronic DiseaseAnemia of Chronic Disease
Iron DeficiencyIron Deficiency Can result from:Can result from:
Pregnancy/lactationPregnancy/lactation Normal growthNormal growth Blood lossBlood loss Intravascular hemolysisIntravascular hemolysis Gastric bypassGastric bypass MalabsorptionMalabsorption
Iron is absorbed in proximal small bowel; Iron is absorbed in proximal small bowel; decreased abosrption in celiac disease, decreased abosrption in celiac disease, inflammatory bowel diseaseinflammatory bowel disease
May manifest as PICAMay manifest as PICA Tendency to eat ice, clay, starch, crunchy Tendency to eat ice, clay, starch, crunchy
materialsmaterials May have pallor, koilonychia of the nails, May have pallor, koilonychia of the nails,
beeturiabeeturia Peripheral smear shows Peripheral smear shows microcytic, microcytic,
hypochromic red cells with marked hypochromic red cells with marked anisopoikilocytosisanisopoikilocytosis..
Iron Deficiency Anemia - koilonychiaIron Deficiency Anemia - koilonychia
IroIron in n in
the the BoBodydy
Serum TransferrinSerum Transferrin((Beta-globulinBeta-globulin).).
Main function - transport of absorbed iron in the depot Main function - transport of absorbed iron in the depot (liver, spleen), into the medullary erythroid (liver, spleen), into the medullary erythroid predecessors and into the reticulocytes. predecessors and into the reticulocytes.
Basic place of synthesis - liver. Basic place of synthesis - liver. An increase in the content of transferrin with lowering An increase in the content of transferrin with lowering
in the level of iron of serum is characteristic for the in the level of iron of serum is characteristic for the iron-deficiency state. iron-deficiency state.
A decrease in the level of transferrin can be with the A decrease in the level of transferrin can be with the damage of the liver (different genesis) and with the damage of the liver (different genesis) and with the loss of protein (for example, in nephrotic syndrome). loss of protein (for example, in nephrotic syndrome).
The level of transferrin is increased in the last term of The level of transferrin is increased in the last term of pregnancy. pregnancy.
TransferrinTransferrinLIMITATION The concentration of TF is subjected to the The concentration of TF is subjected to the
daily variations daily variations Acute inflammation contributes to lowering Acute inflammation contributes to lowering
the TF levelthe TF levelCLINICAL SIGNIFICANCE Basic clinical index for the differentiation Basic clinical index for the differentiation
between the iron-deficiency ([TF]↑) and between the iron-deficiency ([TF]↑) and hemolytic anemia ([TF]↓) hemolytic anemia ([TF]↓)
More precise index than total iron binding More precise index than total iron binding capacity capacity
After the liberation of iron from the After the liberation of iron from the complex, TF ion of Fe3+ must be restored complex, TF ion of Fe3+ must be restored into Fe2+ into Fe2+
FerritinFerritin water-soluble complex of iron water-soluble complex of iron
hydroxide with the protein hydroxide with the protein apoferritin.apoferritin.
It is located in cells of the liver, It is located in cells of the liver, spleen, bone marrow, in the spleen, bone marrow, in the reticulocytes. reticulocytes.
Ferritin is the basic protein in Ferritin is the basic protein in human which deposits iron and human which deposits iron and concentration of ferritin in the concentration of ferritin in the serum reflects the reserve of iron serum reflects the reserve of iron in the organism. in the organism.
Iron Deficiency Anemia – Lab Iron Deficiency Anemia – Lab FindingsFindings
Serum IronSerum Iron LOWLOW (< 50 micrograms/dL) (< 50 micrograms/dL)
Total Iron Binding Capacity (TIBC)Total Iron Binding Capacity (TIBC) HIGHHIGH ( > 360 micrograms/dL) ( > 360 micrograms/dL)
Serum FerritinSerum Ferritin LOWLOW (< 20 nanograms/mL) (< 20 nanograms/mL) Can be “falsely”normal in inflammatory Can be “falsely”normal in inflammatory
statesstates
Treatment of Iron Deficiency AnemiaTreatment of Iron Deficiency Anemia
Oral iron saltsOral iron salts Ferrous sulfate – 325 mg(50 mg Ferrous sulfate – 325 mg(50 mg
absorption)absorption) Side effects: constipation, black stools, Side effects: constipation, black stools,
positive hemmoccult testpositive hemmoccult test Vitamin C can facilitate iron absorption.Vitamin C can facilitate iron absorption.
Treatment of Iron Deficiency Treatment of Iron Deficiency AnemiaAnemia
Diet: meat, liver, yeast, fishDiet: meat, liver, yeast, fish Oral preparations: recovery rate Hb Oral preparations: recovery rate Hb
does not differ from parenteral does not differ from parenteral introduction, side effects are less, introduction, side effects are less, excessive introduction does not lead excessive introduction does not lead to hemosiderosis. to hemosiderosis.
- Dosage : 1 hour prior to the meal- Dosage : 1 hour prior to the meal
in the evening time (absorption in the evening time (absorption increase in the second-half of a day) increase in the second-half of a day)
Possibilities : dark colour of stool and Possibilities : dark colour of stool and transitory dyspeptic disorders (nausea, transitory dyspeptic disorders (nausea, diarrhea or watery stool) diarrhea or watery stool)
Check analysis of the blood: in 7-10 days – Check analysis of the blood: in 7-10 days – reticulocyte reaction; 4 weeks - increase Hb reticulocyte reaction; 4 weeks - increase Hb and Htand Ht
- Iron tolerance test(2 tablet-2 h-100 micro/dl- Iron tolerance test(2 tablet-2 h-100 micro/dl
During the normalization of the indices of the During the normalization of the indices of the blood – reduce the dose of preparationblood – reduce the dose of preparation
Parenteral Introduction of IronParenteral Introduction of Iron
in exceptional casesin exceptional cases in severe iron deficiency anemiain severe iron deficiency anemia intolerance of oral preparations (after repeated intolerance of oral preparations (after repeated
replacement and reduction in the dose)replacement and reduction in the dose) diseases of gastro-intestinal tractdiseases of gastro-intestinal tract syndrome of the disrupted intestinal absorbtionsyndrome of the disrupted intestinal absorbtion after the extensive resection of the small after the extensive resection of the small
intestineintestine continuous blood losscontinuous blood loss
Complications of Parenteral Complications of Parenteral IntroductionIntroduction
Local reactions (pains, phlebitis)Local reactions (pains, phlebitis) General reactions (anaphylaxis, fever, General reactions (anaphylaxis, fever,
head and articulate pains, vomiting, head and articulate pains, vomiting, rash, bronchospasm). rash, bronchospasm).
Preparations: Preparations: Venofer - for the intravenous Venofer - for the intravenous
introduction,introduction,Maltofer, Ferrum-Lek - intramuscularMaltofer, Ferrum-Lek - intramuscular
Overdose of IronOverdose of Iron
In the first 6-8 hours - epigastral pains, In the first 6-8 hours - epigastral pains, nausea, vomiting (including with the blood), nausea, vomiting (including with the blood), diarrhea, pallor, sleepiness, acrocyanosis)diarrhea, pallor, sleepiness, acrocyanosis)
For 12-24 hours - metabolic acidosis, For 12-24 hours - metabolic acidosis, leukocytosis, there can be spasms, coma, leukocytosis, there can be spasms, coma, after 2-4 days - necroses of the liver and after 2-4 days - necroses of the liver and kidneys.kidneys.
Treatment: emetic means, stomach Treatment: emetic means, stomach lavage, the method of milk with the egg lavage, the method of milk with the egg white, Deferoksamin, Desferal, symptomatic white, Deferoksamin, Desferal, symptomatic therapy. therapy.
Iron Overload SyndromeIron Overload Syndrome Human does not have special mechanism of the Human does not have special mechanism of the
excretion of iron! Its excessive introduction leads to excretion of iron! Its excessive introduction leads to hemosiderosis. Clinical manifestations: Gradual hemosiderosis. Clinical manifestations: Gradual increase of the dimensions of the liver, spleen, increase of the dimensions of the liver, spleen, cardiopathy, suprarenal insufficiency, diabetes cardiopathy, suprarenal insufficiency, diabetes mellitusmellitus
Laboratory signs: Laboratory signs:
Increase in serum iron (more than 30 mmol/liter), Increase in serum iron (more than 30 mmol/liter), percentage of saturation transferrin by iron it is percentage of saturation transferrin by iron it is more than 50%, ferritin of serum it is more than more than 50%, ferritin of serum it is more than 1000 ng/ml1000 ng/ml
Megaloblastic AnemiaMegaloblastic Anemia
A subclass of macrocytic anemia A subclass of macrocytic anemia
(under morphologic classification)(under morphologic classification)
OrOr A subclass of anemias due to A subclass of anemias due to
defective DNA synthesis defective DNA synthesis
(pathogenetic classification)(pathogenetic classification)
Vit.B12Vit.B12
Average diet contains Average diet contains 5 – 305 – 30 g Vit. Bg Vit. B1212 dailydaily
The amount of Vit. BThe amount of Vit. B12 12 in the body is about in the body is about 2 – 52 – 5 mg. mg.
Most of it is in the liver. Most of it is in the liver. The store is sufficient for The store is sufficient for 3-63-6 years in case years in case
of impaired absorbtion.of impaired absorbtion. The storage form is mainly The storage form is mainly
adenosylcobalamin. adenosylcobalamin.
stomach
Enterohepatic circulation
Ileum cells
Pancreas enzymes
Parietal cell
Duodenum and jejunum
B12 in diet R-Binder
R - B12
R- B12
B12 B12
IF B12
TC II
B12
İleum
IF
IF - B12
Functions of Vit.BFunctions of Vit.B1212
2- 2-
Methyl FHMethyl FH44 FHFH44
HomocysteinHomocystein MethioninMethionin SAMSAM
BB1122
Methionin synthase
Vit.B12Vit.B12
Food sources rich in Vit.B12Food sources rich in Vit.B12 LiverLiver KidneyKidney MuscleMuscle EggEgg Milk ,Cheese and other diary productsMilk ,Cheese and other diary products SeafoodSeafood
Folic acidFolic acidDaily requirementsDaily requirements
AgeAge
0 - 10 0 - 10 3.63.6g /kg g /kg > 10 > 10 33g /kgg /kg Pregnants Pregnants 500 500 g g Lactation +100 Lactation +100 g g
Diet contains 100 - 500 Diet contains 100 - 500 g folate/dayg folate/day..
Folate absorbtionFolate absorbtion
Mainly jejunum. Mainly jejunum.
In the form of monoglutamate . In the form of monoglutamate .
Methyltetrahydrofolate monoglutamate Methyltetrahydrofolate monoglutamate is is
the form it is found in serumthe form it is found in serum . .
Folate levels:Folate levels:
Normal rangesNormal ranges Serum:Serum: 6 – 21 6 – 21 g/L g/L (RBC volume) (RBC volume)
Red cell: Red cell: 160 – 640 160 – 640 g/L g/L (RBC volume)(RBC volume)
Folate deficiencyFolate deficiency Serum folate : Serum folate : <4<4g /L g /L Red cell folate: Red cell folate: <140<140g /Lg /L
Folate storesFolate stores
Total body folate:Total body folate: 5 – 20 mg 5 – 20 mg
Storage place :Storage place : LiverLiver
Storage form: Storage form: Methyl-Methyl-FHFH44
polyglutamatepolyglutamate
Dihydrofolate
THFA
Methylene
THFA
Deoxyuridilate Thymidilate DNA-thymine
Methyl THFA
Homocystein
Methyonine
B12
Dihydrofolate reductaseserine
glycine
Thymidylate synthase
Tissues or organs other than bone Tissues or organs other than bone marrow are also affectedmarrow are also affected
Skin,GIS, female genital system mucosal Skin,GIS, female genital system mucosal epitheliumepithelium
Congenital abn.(neural tube defects)Congenital abn.(neural tube defects) Neurologic changesNeurologic changes(Vit.B(Vit.B1212 deficiency) deficiency)
Peripheral neuropathyPeripheral neuropathy Subacute combined degeneration of spinal cordSubacute combined degeneration of spinal cord Cerebral -Mental changesCerebral -Mental changes
HyperhomocysteinemiaHyperhomocysteinemia
Clinical findings(1)Clinical findings(1) Anemia:Anemia:
Symptoms of anemia + palor+slight icterusSymptoms of anemia + palor+slight icterus
Glossitis :Glossitis :
Sore tongue, poor taste sensation, painSore tongue, poor taste sensation, pain
Papill. atrophy-beefy tonguePapill. atrophy-beefy tongue
RBC Indexes:RBC Indexes:
MCVMCV MCHMCH RDWRDW
Biochemical findingsBiochemical findings
LDHLDH ( LDH -1> LDH - 2)( LDH -1> LDH - 2) Bilirubin(indirect) Bilirubin(indirect) Ferritin and serum iron Ferritin and serum iron Haptoglobin Haptoglobin
Criteria of Effective TreatmentCriteria of Effective Treatment
Subjective improvement during the first Subjective improvement during the first days of treatment;days of treatment;
Reticulocytosis, maximally expressed (to Reticulocytosis, maximally expressed (to 20%) on 5-720%) on 5-7thth day of treatment; day of treatment;
Increase in hemoglobin and number of Increase in hemoglobin and number of erythrocytes, beginning from the 2nd erythrocytes, beginning from the 2nd week of treatment; week of treatment;
The normalization of the blood index, The normalization of the blood index, number of leukocytes and thrombocytes number of leukocytes and thrombocytes in 3-4 weeks of treatment. in 3-4 weeks of treatment.
AnemiaAnemiaCase Study #1Case Study #1
A 72 year A 72 year old male old male has the CBC has the CBC findings findings shown. shown. Peripheral Peripheral RBCs are RBCs are hypochromihypochromic & c & microcytic.microcytic.
AnemiaAnemiaCase Study #2Case Study #2
A 48 year old male A 48 year old male has become has become progressively progressively more fatigued at more fatigued at the end of the day. the end of the day. This has been This has been going on for going on for months. In the months. In the past month he has past month he has noted paresthesias noted paresthesias with numbness in with numbness in his feet. A CBC his feet. A CBC demonstrates the demonstrates the findings shown.findings shown.
Case #3Case #3
Labs:Labs: Hgb: 5.1 g/dLHgb: 5.1 g/dL MCV: 112MCV: 112 RDW: 21%RDW: 21% Platelets: 109Platelets: 109 WBC: 4.6WBC: 4.6
Case #3Case #3 Which of the following blood levels Which of the following blood levels
are most likely in this patient?are most likely in this patient?
Vitamin B12
Folate Methylmalonic Acid
Homocysteine
(A) Low Normal High High
(B) Low Normal Normal High
(C) Normal Low High Normal
(D) Normal Low Normal High
(D) Normal Normal Normal Normal