 Congenital adrenal hyperplasia results because of the deficiency of enzymes which are required in the synthesis pathway of various adrenal cortical hormones. So this flowchart shows the pathway of the synthesis of the various adrenal cortical hormones. Fundamentally there are three pathways going on. See the first one here is for the synthesis of the mineralocorticoid that is the aldosterone. Second one is showing the pathway for the synthesis of the glucocorticoids and here the last one is showing the synthesis of the adrenal androgens. Now for understanding congenital adrenal hyperplasia some basics you should get here first. First thing is that if there is a deficiency of any enzyme say suppose there is deficiency of this enzyme then the forward reactions will not be able to proceed and the hormone which is synthesized in the forward reaction will not be synthesized. Secondly the back products will accumulate because they are not able to undergo the process. Also because of the deficiency of these hormones the negative feedback which operates that is the glucocorticoid inhibiting the release of CRH from hypothalamus and ACTH from pituitary. This will not be operative because the end products are not being synthesized isn't it? So more of this ACTH and CRH will be synthesized which will act on this pathway and hence there will be more and more accumulation of the back products. So one is accumulation of the back product that the forward synthesis of the hormone is not taking place and secondly because of the increase in the stimulating hormones due to the loss of the negative feedback these back products will further accumulate. So due to the accumulation of the back products actually the pathway can proceed in other directions. You see in the first two reactions actually these initial products that is the pregneralon and progesterone are actually moving horizontally also. So this is basically synthesizing the cortisol and also the androgens. Similarly the 17-hydroxy-pregneralon and 17-hydroxy-progesterone is also being used for the synthesis of cortisol as well as for the synthesis of the adrenal androgens. So two things forward reaction doesn't take place. Second the backward products accumulate which are diverted to the synthesis of the other hormones. So with these fundamentals let us see what are the various enzyme deficiencies which can cause congenital adrenal hyperglacia. Okay first let's see the most important one and that is the deficiency of 21 hydroxylation. So 21 hydroxylase is deficient. So we look at the pathway and see what can be the problems. By the way I have already explained the pathway and how to remember that in another video. I have given the link for that in the description section below. You can check that out also. Anyway so we were talking about that 21 hydroxylase deficiency. Okay one thing here that physiology books have mentioned this enzyme as 21 beta hydroxylase but other books have mentioned it as 21 alpha hydroxylase. But doesn't matter we will remember it as 21 hydroxylase deficiency. So what is going to happen is that you see that this 21 beta hydroxylase is required both for the synthesis of mineralocorticoid as well as the glucocorticoids. So these forward reactions will not be able to proceed. So obviously the deficiency will cause decrease in the glucocorticoids as well as decrease in the mineralocorticoids. In addition these packed products are going to accumulate and obviously they will be diverted for the synthesis of the adrenal androgens because these two pathways are blocked they cannot proceed further. Hence there will be increase in the adrenal androgens. So how do these patients present basically we are saying that it is a congenital deficiency of the enzyme. So obviously in severe form it is present in children. So how do these children present? See because of the increase in the adrenal androgens females will have amdiguus genitalia. So in any case of female with amdiguus genitalia it is very important that we suspect the congenital adrenal hyperplasia and that too 21 hydroxylase deficiency because it is the most common one. Secondly because of the deficiency of mineralocorticoids whose main function is to absorb salt from the kidneys and if salt is absorbed water follows that. So basically salt and water absorption occurs in kidney by aldosterone or mineralocorticoid. So there is salt wasting. So there is a loss of salt in urine and along with that there is loss of water also. So obviously that can cause polyuria that is increased frequency of urination and due to excess loss of water the patient can land into circulatory shock. So it is very important to identify this problem in early stage. Then glucocorticoid deficiency also lead to inability to maintain growth or loss of weight will occur. So what we call as failure to thrive. In addition because of the loss of the negative feedback we said that there will be increase in the release of the ACTH and along with that melanocytostimulative hormone is also released which causes hyperpigmentation. So these patients will have hyperpigmentation. So these are the various clinical features of 21 hydroxylase deficiency and we can very well understand it if we know the basic physiology which is operating. Moreover the diagnosis of 21 alpha hydroxylase deficiency also depends on checking the levels of 17 hydroxy progesterone in blood. So since the pathway is blocked this chemical accumulates in blood and its levels can increase up to 1000 to 2000 times than normal. Okay just last point we will make about 21 hydroxylase deficiency because we have covered so much. We should also know about the morphological changes which can occur. See because of the increase in ACTH this increased ACTH will act on the adrenal cortex and this will lead to proliferation of the adrenal cortical cells leading to hyperplastic adrenals that is the size of the adrenal gland will increase because of the increase in the number of the cells and since it is the cortical hormone so there will be widening of the cortex because this ACTH acts on the adrenal cortex. So these are the morphological features which occur in the adrenal that is the reason that it is known as congenital adrenal hyperplasia which is occurring due to the deficiency of the enzyme. Okay so now let's go to other enzyme deficiencies which are less important but may occur and hope after knowing this you will be easily able to tell what will be the features in other kind of deficiencies. So next deficiency which we'll see is a deficiency of 11 beta hydroxylase. So this enzyme you see is required here in the pathway so obviously these steps will not occur and there will be deficiency of the glucocorticoids so let's write it glucocorticoids will be less and logically mineralocorticoids will also be less but what happens is this product 11 deoxy corticosterone also has lot of mineralocorticoid activity. So because of the accumulation of this product actually what we get is features of increase in mineralocorticoid. So the patient will present with hypertension actually because there will be more salt and water absorption which will lead to hypertension and what about androgens? Yes again because of the accumulation of the back prototypes androgens will be increasing. So here again there will be increase in the androgens. So see these enzyme deficiencies which lead to increase in the androgens which lead to ambiguous genitalia in females and if the enzyme deficiency is less severe then it also manifests in males as a precocious puberty little later in life. So these are also known as androgenital syndromes okay fine. Now let's see what is the third enzyme deficiency. Let's talk about deficiency of enzyme 17 alpha hydroxylase. So if this enzyme is deficient you can see that it will not affect this pathway it will go on and there will be increase in the synthesis of the aldosterone because the entire prognome will be used in the synthesis of the aldosterone. But these two pathways will be affected because the precursors will not proceed in these directions. So what we will see here is again decrease in the synthesis of the glucocorticoids increase in the synthesis of the mineralocorticoids and androgens in this case will be less not more okay. Final enzyme deficiency which we will we will see is this enzyme 3 beta hydroxy steroid dehydrogenase. Now you see this enzyme is required across pathways in all the three pathways it is required. So basically these will be deficient but you see the first pathway it can go uncontrolled and there will be synthesis of excess dehydro epiandroosterone. So what we are seeing here again with the deficiency of 3 beta hydroxy steroid dehydrogenase is there is deficiency of glucocorticoid there is deficiency of mineralocorticoid and there are increased androgens in this case basically here also I should have used green because of increased. Anyways I think you must have got the point. Okay just to summarize how to remember all this basically you see in all types of deficiencies glucocorticoids are decreasing in all these types of deficiencies. Mineralocorticoids they are decreasing into and increasing into in 11 and 17 hydroxylation deficiency they are increasing. So I remember it like this I just write this 11 and 17 and mineralocorticoid increases. So in 11 and 17 hydroxylase deficiency mineralocorticoids will increase and the rest it will decrease and androgens you see they are increasing in all except 17 hydroxylase deficiency. So that's the way to remember it glucocorticoids decrease in all deficiency in 11 and 17 hydroxylase deficiency mineralocorticoid increase in the other two they decrease and androgens decrease in 17 hydroxylase deficiency but increase in all three and if you understand it by the means of pathway then it will be much easier to remember also. Okay everyone so that was about congenital adrenal hyperplasia. I hope you have understood that why adrenal hyperplasia is going to occur because of increase in ACTH. Hopefully you have understood what will be the clinical features depending on the increase or the decrease in the various types of hormones. Well thanks for watching the video. 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