Basic Pathology of Anemia |Pathology|

Hi there! =)
I’m thinking of discussing on Anemias today. Ok, here I just would like to do somekind of introduction towards Anemias. More or less, I will try to discuss on definition, basic pathogenesis, classifications, outcomes or perhaps some medical terms that we really need to know along the way.
Ok, guys, let us get into medical adventure of anemias lol (it’s not funny? Ok fine! -____-“)

Definition
(Kumar, et al: Robbins Basic Pathology. Red cell disorders 12:422, 2007)

1) Reduction in oxygen carrying capacity of blood
2) characterized by reduction in the total circulating red cell mass to below the normal range

Basic Pathogenesis
Anemia can be due to
1) Excessive bleeding (heamorrhage). Such as trauma

2) Increased in RBC destruction. Such as heamolytic anemias

3) Decreased in RBC production. Such as Iron Defeciency anemia.

Those are the most common causes of anemias. It is important to know the reasons (factors) that lead to anemia cause it is the basis of classification of anemia. Remember, good classification leads to better diagnosis, good diagnosis will give a good treatment. Doctor who gives good treatment is simply a good doctor =)

Ok, let us take anemias as whole, cause there are countless types of anemias since some of anemias are due to genetic disorders.
There are few basic classifications of anemias based on different approaches

1) Classification of anemias based on pathogenesis
a) Heamolytic anemia ( increased destruction)
  -Membrane abnormalities
Spherocytosis
-Enzymes deficiencies
G6PD
-Disorder in heamoglobin synthesis
Thalassemia (Deficient globin synthesis)
Sickled cell anemia (Unstable heamoglobin)

b) Impaired Production
   -Disturbance in proliferation and maturation of erythroblast
Megaloblastic anemia
-Defective heme synthesis
Iron deficiency anemia
-Defective globin synthesis
Thalassemias

2) Classification based on morphology
There are few terminologies which need to be understood in the morphology of red cells in anemias

a) Cell size
    Normocytic (normal)
-hereditary spherocytosis
-sickle cell
Macrocytic (large)
-megaloblastic anemia
Microcytic (small)
-iron deficiency anemia
-thalassemia
b) Degree of hemoglobinization
    Normochromic (normal)
-Hemolytic anemia
Hypochromic (pale)
-Iron deficiency anemia

That is a handful of list isn’t it? Nevermind, we can take it one step at a time.

The immediate body response towards anemias are
-Dyspnea
-Organ failure (severe)
-Hypovolumic shock (severe)

Ok, we know that anemia has a marked decreased in oxygen carrying capacity.
The reduction in oxygen number blood somehow triggers the increase in erythropoeitin (hormone controlling the erythropoeisis) secretion by KIDNEY.
This will lead to these consequent events :-

1) Compensatory erythropoesis in the red bone marrow which leads to erythroid precursor hyperplasia

2) In further extent or chronic condition, erythropoesis can even happen outside the red marrow; this is called as extramedullary erythropoesis.

3) Because of the increased of RBC production, erythroblast couldn’t even have time to mature and they tend to exit the red marrow and enters the peripheral blood. The increased number of reticulocytes (immature RBC) in peripheral blood is called as RETICULOCYTOSIS.

4) Too many activity that should be done by the red marrow makes it to try to compensate its workload by expanding its volume. This leads to red marrow expansion which eventually defects the shape of a bone. But remember, it can only expand its volume towards some extent, if it has reached its limit, extramedullary erythropoesis will take part.

5) If the anemia is a hemolytic anemia, there is increased in the destruction of red cells. And destruction of red cells mostly happens outside the blood vessels (extravascular hemolysis). Now, it has already involved the reticuloendothelial system (consists of liver and spleen). Try to imagine, when there are extramedullary erythropoesis and extravascular hemolysis happened simultaneously at liver and spleen, doesn’t it increase the workload of both organs? These extensive activities will finally lead to Hepatosplenomegaly (enlargement of liver and spleen)

6) Also, when there is increased in hemolysis, it will lead to the accumulation of iron in the blood and tissue. Accumulation of iron in tissue (hemosiderosis) will eventually leads to the destruction of tissue (hemochromatosis). It will ultimately lead to endocrine failure (usually pancrease and liver) and heart failure.

Those are the generalised pathogenesis of anemias.

Ok, that was a long and mouthful explanation lol. Now I would like to list down terms that we really need to know :-

Mean Corpuscular Volume – average VOLUME of heamoglobin in a red cell

Mean Corpuscular Hemoglobin – average MASS of heamoglobin in a red cell

Mean Corpuscular Heamoglobin Concentration – average CONCENTRATION of hemoglobin in a given volume of red cells

Erythropoesis – process of formation of erythrocytes (RBC) in the red marrow of a bone (long bone in children while flat bone in adults)

Erythropoetin – hormone releases by peritubular capillary endothelial cells of the KIDNEY to regulate erythropoesis

Extramedullary erythropoesis – erythropoesis that happens outside the medulla of bone, usually at the reticuloendothelial system (liver and spleen)

Hemolysis – process of destruction of RBCs which usually happens at the liver and spleen and done by mononuclear phagocytic cells; Kupffer cells in the liver and splenic macrophage in the spleen.

Hepatosplenomegaly – enlargement of liver and spleen due to compensatory mechanism

Hemosiderosis – accumulation of iron in tissue without presenting any tissue damage

Hemochromatosis – accumulation of iron in tissue with marked tissue damage

Those are pretty much about the general ideas on anemias. We will discuss extensively on different types of anemia individually, so we would have a better sight about this common disease.
Hope this article will help you in any way, and not to forget, please read more, cause the only way for you to understand medicine is through reading. Thank you so much and goodluck! =)

Why we cannot give Bacteriocidal and Bacteriostatic antibiotics together? |Pharmacology|

Ok, now let us take a little bit of time to squeeze our head and try to figure out the answer- Why we cannot give bacteriocidal and bacteriostatic antibiotics together?

Let us do some quick revision on the fundemental knowledge of antimicrobial therapy

Bacteriostatic – These agents do not kill the bacteria but rather stopping it from replicating to produce more progeny bacteria such as by interrupting protein sythesis
Example :-
Choramphenicol
Tetracycline
Macrolides

Bacteriocidal – These agents can simply kill the bacteria by disrupting the intergrity of cell wall; peptidoglycan
Example :-
Penicillin
Cephalosporin
Carbapenem
Monobactam
Glucopeptide

Lets see, what if I give Tetracycline (bacteriostatic) together with Penicillin (bacteriocidal)? What will happen? Are they synergizing each other, or antagonizing each other?
Ok, let us take one step at a time; we try to enumerate the mechanism of action of Tetracycline and Penicillin separately

Tetracycline
1) It acts by inhibiting 50S ribosomal subunit and inhibiting the binding of tRNA to the A site on the 30s ribosomal subunit.

2) As we all clear, protein synthesis is crucial for cell to replicate as it needs to double it’s cellular components in order to divide into 2 progeny cells.

3) When protein synthesis is halted, cell doesn’t have enough protein to get ready for replication. Thus, it wont divide

4) So, the bacteria remains dormant and eventually weakens and make it easy to be destroyed by immune cells.

Penicillin
1) I do realize that we all know that there are extensive subgroup of penicillin such as methicillin, amoxycillin and etc, but let us take it as a whole.

2) It acts by inhibiting the cross linking of nascent (NEW) peptidoglycan through binding to Penicillin Binding Protein (PBP).

3) It must be clear that cross linking only happens when there is a NEWLY synthesized peptidogycan

4) Ting Tong! Ok, lets see, peptidoglycan can only be synthesized when the cell is starting to replicate. Of course it needs new peptidoglycan, cause it needs to divide into two, remember? If not, there wont be enough peptidoglycan for the cell to give rise to 2 progeny cells

Ok, now let us get back to our 1 billion dollar question – Why we cannot give bacteriostatic together with bacteriocidal antibiotics?

If you give Tetracycline, it will eventually stop bacterial replication.
Without replication, there will be no synthesis of new peptidoglycans.

Without new peptidoglycans, there will be no cross linking.

Without cross linking, Penicillin couldn’t elicit its response.

So, we can see there is an antagonism happening between Tetracycline and Penicillin.
Different author has different opinion, but most of them believed that Tetracycline reduces Penicillin action into half.
Therefore, Tetracycline and Penicillin are said to be antagonizing with each other.

In what condition does antibiotics give synergistic effect between each other?

Let me put it in a simple way, synergism only happens when we give two antibiotics which have different mechanism of actions but lead to same final result.
Let me give a very popular example of synergism in antibiotic therapy = Bactrim® (Sulfamethoxazole plus Trimethoprim)

1) Both Sulfamethoxazole and Trimethoprim are folate synthesis inhibitor

2) Sulmathoxazole is a false substrate of Dihydropteroate Synthatase. It acts by competitivey inhibiting the enzyme. Inhibition of this enzyme will reduce the production of Dihydrofolate Reductase which is essential in synthesizing Tetrahydrofolic Acid.

3) Trimethoprim on the other hand, inhibits the Dihydrofolate Reductase itself. Thus inhibits the production of Tetrahydrofolic Acid.

4) So, we get it now! Both antibiotics will ultimately reduce the production of Tetrahydrofolic Acid. It must be clear that bacteria cannot take folic acid from the environment, it solely depends in de novo folic acid. Inhibition of production in Tetrahydrofolic Acid will stop replication cause folic acid is precursor to DNA nucleosides. Eventually bacteria will starve and unable to replicate.

5) See, both inhibit different enzymes but ultimately leads to same final result which is the reduction in production of Tetrahydrofolate Acid.

6) Bactrim® successfully use in the treatment of
Respiratory tract infection
Urinary tract infection
Gastrointestinal tract infection

Thats all from me for today, hope it helps you people =) Goodluck by the way