Ok let us now talk about Pathology. Previously, we already discussed on the basic pathology of anemias, but today we gonna talk about specific pathology for Hemolytic Anemias.
There are several types of hemolytic anemias which we gonna discuss in detail in separate post, but for the time being let us take it as a whole.
Below is the list of the most commonly occurring hemolytic anemias with its causes:
1) Heriditary Spherocytosis
+Deformed structure of erythrocytes
-85% autosomal dominant trait
-25% autosomal recessive (often severe case)
2) Sickle Cell Anemia
+Deformed structure of Beta globin chain
+Missense mutation (point mutation), SUBSTITUTION (glutamic acid to valine)
+Replacement of HBA1 to HBS
-Homozygous leads to 100% of HBS replacement
-Heterozygous leads to 50% of HBS replacement
+Co-dominant autosomal genetic disorder
+Due to gene DELETION which leads to frameshift mutation
-Beta thalassemia (chromosome 16)
+Homozygous – Major thalassemia
+Compound heterozygous – intermediate thalassemia
+Heterozygous – trait, asymptomatic
-Alpha thalassemia (chromosome 11)
a) –/– – Hydrops fetalis; fatal in utero
b) –/-a – moderately severe
c) –/aa – alpha thalassemia trait
d) –a/aa – silent carrier, asymptomatic
4) Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
+Defective in G6PD gene at the X chromosome
+Less activity of G6PD
+Red cells vulnerable towards oxidant/free radicals
Like we all agreed, this post will solely discuss on hemolytic anemias as whole. So, let us talk about the general pathogenesis of hemolytic anemias
Hemolytic anemias have 3 major fates that all of them will undergo along the course of the diseases, which are
1) Increased rate of hemolysis
2) Increased compensatory erythropoeisis leads to reticulocytosis (accumulation of reticulocytes in the peripheral blood)
3) Accumulation of by products of hemolysis especially iron
Due to its deformed structure, RBCs of hemolytic anemias are considered to be some kind of foreign bodies. Therefore, there are highly susceptible towards degradation by macrophage – specifically Kupffer cell of the liver and Splenic macrophage of the spleen.
RBCs that already been degraded by macrophage will be change into Heme (iron) and globin (protein, in this case). Heme will eventually turn into bilirubin which will be excreted through bile meanwhile protein will be recycled back.
Due to extensive extravascular hemolysis, bile excretion couldn’t take pace and due to that, bilirubin starts to accumulate in tissues. Increased level of bilirubin (hyperbilirubinemia) will eventually lead to jaundice and it is most prominently seen at the sclera (scleral jaundice).
At the same time, iron is also retained in the body, but when the rate of hemolysis is progressively high, erythropoeisis couldn’t take pace and due to that iron starts to overload. Accumulation of iron (hemosiderosis) will eventually lead to tissue damage (hemochromatosis). The most severely affected organs are the heart and pancreas.
Now, we can see that hemolytic anemias always lead to increased of hemolysis. But the body must do something to it, isn’t it? So, the body starts to release more erythropoietin from the peritubular capillary endothelial cells of the kidney in order to increase the rate of erythropoeisis.
Increased in erythropoeisis will lead to hyperplasia of the erythroid tissue in the red marrow. Therefore, red marrow starts to expand, and eventually compresses the bone and lead to bone deformity. But, it must be clear, compensatory mechanism has its own limit; once it has reached its limit, extramedullary (outside the bone) erythropoeisis will take part.
Extramedullary erythropoeisis involves the reticuloendothelial system – liver and spleen. Those two organs start to increase its activity. We can see that the liver and spleen already do two tasks; hemolysis and erythropoeisis simultaneously. What will happen then? Both organs will start to enlarge. This is called hepatosplenomegaly.
That is pretty much about the general ideas on hemolytic anemias. In next posts, we will discuss in more detail about different types of hemolytic anemia individually.
With that, thank you =)