Download pathology Anaemia : Reduction in the HB concentration below the

pathology
Anaemia : Reduction in the HB concentration below the lower normal limit & it is
usually accompany by reduction in the red cell count .
Normal Hb : adult ♂ 13 – 18 g\dl
♀ 11.5 – 15 g\dl
Sign & symptom :
All anemia share the same non specific sign & symptoms including pallor of skin &
mucus membrane , shortness of breath , easy fatigability .
Classification : (causes) :1- decrease in red cell (RC) production : include
a- disturbance in proliferation & differentiation of stem cell as in aplastic & pure
red cell aplasia .
b- disturbance in proliferation & maturation of red cells as in dyshaemopoietic
anaemia which include :- Iron deficiency anaemia
- Megaloblastic anaemia
- Anaemia of chronic infection & systemic illness
2ab-
increase in RC destruction (hemolytic anaemia):
intrinsic cause :
hereditary spherocytosis : abnormal cell membrane.
glucose 6- phosphate deficiency anaemia : enzyme deficiency .
haemoglobinopathies : abnormal Hb.
extrinsic : due to antibody form against red cells :
haemolytic disease of newborn
blood transfusion reaction
autoimmune hemolytic anaemia (cold & warm )types.
3- anaemia due to blood loss
- acute : as in massive bleeding
- chronic : as in bleeding haemorrhoid & peptic ulcer
Dyserythropoietic anaemia :
Anaemia that caused by deficiency of one or more substance necessary for normal
cell production as iron-VB12 & folic acid
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Iron deficiency anaema :
It is the commonest type of anaemia .normally 5-10% iron absorbed from
duodenum & jejunum , this rate increase in pregnancy.
Iron absorption increase in citric acid , VC , sugar & decrease with milk , tea &
antiacid.
Causes :
1- dietary deficiency . Seen in elderly & infant
2- impaired in iron absorption as in malabsorption syndrome ( iron absorbed in
duodenum mainly).
3- chronic blood lose from GIT ( as in hemorrhoid & peptic ulcer)
4- increase in body demand as in infancy , pregnancy
Haematological finding
1- complete blood picture :
1- low Hb , MCV & MCHC .
WBC &platelets are normal
Reticulocyte count is low.
Blood film : hypochromic microcytic RBC
2- bone marrow : hyperplastic B.M manifest by increase in the number of
normoblast .
Bruccian blue stain for iron
serum iron & serum ferritin are low & increase in iron binding capacity
Clinical features:
In addition to general feature of anaemia , we have koilonychias (spoon shape
finger nail),reduction in prominence of filiform papillae, recurrent oral
ulceration , angular stomatitis ,& pica .
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Megaloplastic anaemia :_
Disorders characterized by impairment of DNA synthesis & characterized by
retardation of nucleous maturation in relation to cytoplasm maturation of red cells
lead to formation of megaloblast in bone marrow & macrocyte in peripheral blood
&it is caused by lack of folic acid or vB12 .
Causes of VB12 deficiency:_
Normal source of VB12 is animal product only & it need intrinsic factor which is
secreted from parietal cell of stomach for its absorption &it usually absorbed from
the ileum. It is heat stable .
1-dietary deficiency seen in vegetarians ..
2-Impaired in the absorption :
*deficiency of intrinsic factor r seen in autoimmune gastritis ,gastric resection & the
condition called pernicious anaemia .
*malabsorption syndrome affect small intestine.
*ileal resection.
3-increase in the requirement as in pregnancy, hyperthyroidism & in malignancy.
Causes of folate deficiency:_
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Folate present nearly in all food &easily destroy by 10-15 heat , so the best source
of folate is fresh food as in vegetables &fruit.
1-Inadequite intake (chronic alcoholism& elderly).
2-Impaired in absorption :mal absorption syndrome, infiltrative disease of small
intestine as lymphoma.
3_Drug such as phenytoin (which interfere with folate absorption ) & methotrexate
(interfere with folate metabolism).
4_Increase requirement as in pregnancy& metastatic cancer.
Clinical features:
1- General feature of anaemia.
2- sore tongue & cheilosis.
3-sterelity may occur.
3-neurological sign which is seen in B12 deficiency only in the form of symmetrical
numbness , burning of feet or hands follow by unsteady gait.
Laboratory diagnosis :_
CBP
- Hb is low . MCV increase but MCHC is normal.
-WBC & platelet normal at the beginning then they become low.
-Reticylocyte low .
-Blood film:
RBC: large & oval(oval macrocytosis). Occasional megaloblast .
WBC: hyper segmented neutrophile (> than 5 lobes).
-Bone marrow :hypercellular & show megaloblast which is larger than normoblast
which show dissociation in maturation between nucleus& cytoplasm i.e the
nucleous still show fine chromatin in orthochromic normoblast.
-Serum assay of VB12 & folic acid .
-schilling test used to differentiate B 12 deficiency due to intrinsic factor
abnormality or due to mal absorption .
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-:
Aplastic anaemia
Significant reduction in haemopoietic marrow (hypoplasia) or sever reduction
(aplasia) result in decrease in RBC,WBC & platelets causing pancytomia
:
Etiology & classification
1 congenital (fanconi anaemia)
2- Acquired :
viral infection
Drug as chloramphinicol
Idiopathic
Radiation
Clinical features-:
Occur at any age with feature of :
1-.anaemia
2-.hemorrhage from various side(skin gum ,vagina(
3-.Infection of mouth & throat
4-.L.N. ,spleen &liver are not enlarge
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Investigation:.
CBP
HB is decreased
WBC : low
Platelets : low
Reticylocyte is low or zero.
Blood film :
RBC is normochromic normocytic sometimes macrocytic.WBC mature .platelets
reduce in number .
B.M aspirate show dry tap.
B.M. trephine biopsy show hypo cellular B.M due to replacement by fat.
Hemolytic anaemia
Anaemia result from increase in RBC destruction ,
Clinical features
1-.general features of anaemia,
2-family history may be positive.
3.--features of haemolysis-: Mild fluctuating jaundice ,splenomegaly ,urine
turn dark on standing due to excess urobilinogen , pigmented gall stone in some
cases.
Thalassaemia
Inherited anaemia caused by decrease in the synthesis of alpha or Beta chain result in alpha
or Beta thalassemia . It is transmitted as autosomal dominant , The heterozygous form called
thalassemia minor (trait) which is asymptomatic or have mild anaemia, while the
homozygous ( Thalassemia major) associated with sever anaemia.
Pathogenesis ;
B- thalassemia :
It is due to point mutation in beta globin gene responsible for synthesis of B chain , in
homozygous state B0 (complete absence of B chain ) while in heterozygous B+ ( reduction
in B chain) .
Two factors related to pathogenesis of B-thalassemia.
1-reduction in B globin lead to inadequate Hb A formation so RBC become hypochromic ,
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2-Formation of excess alpha globin chain form insoluble aggregation which damage the
cell membrane & make cell susceptible to phagocytosis & premature destruction of RBC as
well as the erythroblast , the later form ineffective erythropoeisis.
Alpha thalassemia :
It is due to deletion of alpha globin gene & since we have 4 gene so we have 4 possibilities:
1- deletion of 1 gene ---asymptomatic.
2-delesion of 2 gene ---present as thalassemia minor .
3-delesion of 3 gene ---result in excess 4 B chains form (HbH) or 4 gamma chains (Hb bart)
both hemoglobin cause hemolytic anaemia but less sever than B thalassemia since they
cause less damage to cell membrane.
4- absence of 4 genes --- intrauterine death.
Clinical features :
Thalassemia minor usually asymptomatic or have mild anaemia .
Thalassemia major usually present early in life with feature of anaemia with growth
retardation & skeletal abnormality due to excess erythropoiesis.
With hepatosplenomegaly due to extramedullary erythropoiesis..
* CBP :
Hb : low
WBC & platelets : normal
Reticulocyte count : increase
Blood film morphology : RBCs are hypochromic microcytic with anisopikilocytosis , target
cell & basophilic stippling & normoblast .
* Hb electrophoresis :
In B thalassemia minor : reduction in HbA & increase in HbA2 (2 alpha chain & 2sigma
chain ) .
in B thalassemia major : absence or marked reduction in Hb A with increase in HbF
In alpha thalassemia
presence of 2-4% of Hb H & the remainder consist of HbA , HbA2 &HbF
Prenatal diagnosis by DNA analysis.
Glucose 6-phosphate dehydrogenase deficiency :
It is due to deficiency of g-6.p.d enzyme which is necessary for production of reduce
glutathione which protect the red cell against oxidative injury .so enzyme deficiency make
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RBC susceptible to oxidative injury lead to denaturation of Hb result in intravascular
hemolysis.
The gene responsible for Glucose 6-phosphate dehydrogenase is located on X chromosome
so the disease is appear in male while the female is carrier .
The disorder produce symptom when the red cell expose to oxidative stress caused by drug
(antimalaria ,sulfonamide , aspirin & VK ), infection & toxin &bean.
Clinical features : it develop 2-3 days after exposure to oxidizing agent & present with dark
urine (Hb in urine)with jaundice
Sickle cell anaemia :
Hereditary anemia characterized by the presence of abnormal Hb (Hb S)
Pathogenesis : mutation in B –globin gene result in replacement of glutamic by valine at
position 6 , so on de-oxygenation Hbs undergo polymerization (crystallization) so the RBC
change from biconcave to sickle shape which is reversible on oxygenation , later it become
irreversible. This result in :
1- Premature destruction in the spleen .
2- sickling cause widespread obstruction in microcirculation causing ischemia mainly in the
spleen , bone & kidney .
Two form of disease are found , Sickle cell anemia which is seen in homozygous , & Sickle
cell trait seen in heterozygous .
Clinical features:
*Disease appear at 6 months when HB F is replaced by Hbs.
*Feature of sever anaemia .
*Evidence of hemolysis as jaundice & hepatospleenomegaly , later on spleen shrink
(autospleenectomy)
*pain crisis due to vaso-occlusive occur at any site but most common in the B.M giving rise
to fat embolism which may complicate by acute chest syndrome or CNS stroke.
* aplastic crisis :sudden & temporary cessation of erythropoiesis which trigger by viral
infection cause worsening of anaemia & absence of reticulocyte ,
Laboratory findings :
* CBP :
Hb : low
WBC & platelets : normal
Reticulocyte count : increase
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Blood film morphology : RBCs are normochromic normocytic with anisopikilocytosis ,
target cell & sickle cell & normoblast .
* Hb electrophoresis : presence of HbS.
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Sickling can be induced by creating state of hypoxia by using Na met bisulfate.
Autoimmune HA :
Group of anaemia due to antibody production against its own RBCS.& it is of 2 types ;
Warm Ab AIHA; in which the AB is of IgG which are active at 37 c .
Pathogenesis is due to opsonization of RBC so RBC lost part of its wall & become spheroid
(acquire spherocytosis) & this enhance its phagocytosis by spleen.
Causes:
*Idiopathic.
*secondary to other disease as SLE ,NHL, CLL & drug as penicillin & methyl dopa.
Clinical feature :
Chronic anaemia with remission & relapse .
Spleenomegaly with jaundice,
Diagnosis:
Anaemia of norm chromic normocytic with spherocytosis & reticylocytosis
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Direct comb test is +ve due to the presence of antibody on the RBC .
Indirect comb test is +ve due to the presence of free Ab in the serum .
Occasional thrombocytopenia,
Cold agglutinin HA :
Antibody of IgM against I A.g on red cell & by presence of C3b hemolysis occur at low
temperature due to opsonization & usually intravascular .
.clinical features :
Chronic anaemia worse due to cold exposure.
Cyanosis of tip of finger , nose
Hemoglobinaemia & hemoglobinuria on exposure to cold.
.
Causes :
Usually idiopathic , could be seen in infectious mononucleosis & Mycoplasma pneumonia.
Polycythaemia:
Increase in circulating RBCs with corresponding increase in Hb concentration.
could be relative as in dehydration of any cause OR absolute which is:
 primary (idiopathic)(polycythemia Vera) increase in red cell mass result from
autonomous proliferation of stem cell associated with normal erythropoietin
level.
 Secondary associated with increase erythropoietin :
_ Physiological(appropriate) as in lung disease, cyanotic heart disease , high
altitude .
-Pathological( in appropriate ) as in renal cell carcinoma & hepatoma.
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