2 Etiopathogenesis

Transcript

Coming on to lesson two here i’m in last class we have dealt about the what is the definition, what is what are all the causes, or the conditions that are predisposing to the post hypophosphatemia and the occurrence of the postparturient haemoglobinuria. Now in this class we will see something about what is the pathogenesis?

How postparturient haemoglobinuria is occurring due to hypophosphatemia or other conditioning factors. Etiopathogenesis, as I told you, too many causes are there for Etiopathogenesis of postparturient hemoglobinuria. In case of mammalian red blood cells or dependent on the glucose pathway as the main source of energy in order to maintain the viable structure and function and So, I will deal about this in the next slide. Now coming to how I have given a flow chart showing how this will lead to the pathogenesis of the condition. So the slide is showing about the oxygens that are present in the feed and so how it is going to cause the postparturient Hemoglobinuria. So, oxidants in the feed it will cause the denaturation of the red blood cell skeletal proteins. This will lead to the denaturation of the Hemoglobin. And, the next important thing is heavy drainage of the phosphorus in lactating animals, and also the low phosphorous diet. Both these will lead to hypophosphatemia which in turn is going to cause a oxidative stress in erythrocyte cell wall. So, this will lead to the peroxidation of the phospholipid on erythrocyte lipid bilayer. So, all these and again the third causes Hypocuprosis or Molybdenosis excess of molybdenum or lower level of copper.

This will lead to see, copper as you all know copper is essential for the or it is a cofactor, or it is a important component of certain enzymes like ceruloplasmin and superoxide dismutase. These two are important as an antioxidant factor. Okay so, alteration of this or if there is a copper deficiency this will lead to alteration of the activities of the biological antioxidants like superoxide dismutase and ceruloplasmin. This will result in weakening of the so any antioxidant pathway is affected this will result in weakening of the biological antioxidant system of the erythrocytes will be affected. All this will lead to peroxidation of the Phospholipid, phospholipids of erythrocytes lipid bilayer.

So, this is going to cause the decreased deformability of the red blood cell in micro circulation which will lead to the rupture of the erythrocytes, and that is going to be the release of haemoglobin which will result in the postpartum haemoglobinuria. This is one Etiopathogenesis.

We will see the next flow chart that is showing the another Etiopathogenesis. Here, as I told you the phosphorus deficiency it will lead to hypophosphatemia in detail. I will tell in the next slide how it is causing. So, you see the flow chart. So, hypophosphatemia will be there. This will lead to an impairment of the glycolytic pathway of red blood cells. So, there will be depletion of the ATP synthesis. This depletion of ATP or decrease in the ATP is going to cause the haemoglobinuria in two ways. One is it will lower the glutathione enzyme and also nucleotide sorry nicotinamide Dinucleotide, adenosine phosphate or nicotinamide Adenosine, dinucleotide that combine with the hydrogen ion. This will lead to oxidative stress and further this will cause the intravascular hemolysis. The second way how the depletion of the ATP is going to affect the or it is going to cause the postparturient haemoglobinuria. It is going to make the RBC’s prone for hemolysis because ATP synthesis is decreased so, there will be a decrease in the energy source to maintain the normal function and viability of the red blood cells. So, this will lead to the erythrocytes will become more fragile and there will be a rupture of the erythrocytes releasing the hemoglobin. So, erythrocyte is more prone for hemolysis there will be haemoglobinuria and further haemoglobinuria will be there.

This is one of the flowcharts that is showing the how the haemoglobinuria is going to occur due to copper deficiency. So, reduced activity so, once there is going to be a copper deficiency there is going to be a reduced activity of the copper containing enzymes, like superoxide dismutase. This enzymes are most important because they provide protection against the oxidative stress for the erythrocytes. So, once there is going to be a copper deficiency, there is going to be a oxidative injury to RBC. This will lead to the hemolysis and subsequent haemoglobinuria will be there.

And, next slide we will we are going to see the actual pathogenesis. As I told mammalian red blood cells, it all depends on the glucose metabolism in order to maintain the normal or viable function on the structure. So, it is highly vulnerable to factors that causes the or it impasse the glycolytic pathway. So, what happens is whenever there is a hypophosphatemia there is a decrease in the red blood cell glycolysis which will result in the decrease in the ATP synthesis. So, this abnormal concentration of the atp synthesis is going to alter the normal function and structure of the red blood cell, and there will be a loss of normal deformability, and there will be an increase in the fragility of the red blood cells. And so, this will lead to hemolysis so, there is a release of haemoglobin causing the haemoglobinuria.

Another one, is haemoglobinemia and hemoglobinuria will be the subsequent result of this fragility and hemolysis. And, next thing is the changes, the most important point that is to be remembered in this postparturient haemoglobinuria is changes that are occurring in the red blood cells are irreversible so, and also the lifespan of this red blood cells will be diminished because they are unable to regain its normal or regain its original structure and function. And, the second reason as I told copper and selenium this also plays an important role in the postparturient haemoglobinuria because it provides some protection against the effects of orally ingested hemolytic agents that are present in the cruciferous plants. So, the clinical findings are those of the Hemolytic anemia and death is mainly due to anemic anoxia in postparturient haemoglobinuria. So, in this class we have seen about how individual factors or how individual causes are causing the or leading to the postparturient haemoglobinuria. In the next class we will see something about related to the clinical findings and clinical pathology.

How are we going to diagnose the postparturient haemoglobinuria?