anemia2

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) :-

decrease in red cell (RC) production : include
disturbance in proliferation & differentiation of stem cell as in aplastic & pure red cell aplasia .
disturbance in proliferation & maturation of red cells as in dyshaemopoietic anaemia which include :-
Iron deficiency anaemia
Megaloblastic anaemia
Anaemia of chronic infection & systemic illness

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.


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

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 :

dietary deficiency . Seen in elderly & infant
impaired in iron absorption as in malabsorption syndrome ( iron absorbed in duodenum mainly).
chronic blood lose from GIT ( as in hemorrhoid & peptic ulcer)
increase in body demand as in infancy , pregnancy

Haematological finding

complete blood picture :
low Hb , MCV & MCHC .
WBC &platelets are normal
Reticulocyte count is low.
Blood film : hypochromic microcytic RBC
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 .

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:_

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
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 ,
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 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
Blood film morphology : RBCs are normochromic normocytic with anisopikilocytosis , target cell & sickle cell & normoblast .
* Hb electrophoresis : presence of HbS.

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
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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