 Hi, welcome to Physiology Open. In this video we will see the pathophysiology of diabetes mellitus. To understand diabetes mellitus you should know the functions of insulin on metabolism. In brief we will discuss them in this video. For details you can check out the video on functions of insulin, the link for which is given in the description section below. Diabetes mellitus occurs due to deficiency of insulin function which may occur either due to decreased insulin release or due to decrease in its actions on its receptors which we call as insulin resistance. Both decreased insulin release and insulin resistance obviously decrease the effect of insulin on various limbs of metabolism. So let's first see in brief the actions of insulin which are mainly targeted to reduce the concentration of glucose, fatty acids and amino acids in blood during the fed state when their concentration in blood rises. So for this in liver insulin promotes the conversion of glucose to glycogen that is glycogenesis and also two paths that is lipogenesis while insulin prevents the breakdown of glycogen to glucose that is glycogenolysis and synthesis of glucose that is gluconeogenesis It also prevents the beta oxidation of fatty acids so fats are synthesized while their usage as fuel does not occur. In skeletal muscle it promotes utilization of glucose and its conversion to glycogen and in adipose tissue it promotes storage of fats and inhibits lipolysis. In effect utilization of glucose as energy is promoted and that of fats and amino acids is inhibited. Now when there is deficiency of insulin these actions of insulin are effective. So basically storage and utilization of glucose decreases in fed state leading to increase in blood glucose concentration after food that is post-prandial hyperglycemia occurs. Not only that due to continuing glycogenolysis and gluconeogenesis glucose concentration in blood further increases. See this action in liver that is glycogenolysis and gluconeogenesis continues in between meals too that's why continuously glucose is released into blood so even fasting blood glucose concentration is high. Now normally blood glucose filters in nephron but at normal blood glucose concentration that is about 100 milligram per 100 ml of blood all the filtered glucose is reabsorbed into the blood however in state of insulin deficiency due to excess blood glucose concentration the filtered glucose is also high. This exceeds the capacity of nephron of reabsorbed during the glucose that is transport maximum is reached. Above which the nephrons are not able to reabsorbed further glucose and hence glucose starts appearing in urine that is glucose urea occurs. The presence of glucose in nephron acts as a osmotic pull for water preventing the reabsorption of water also from the nephron. So water loss increases causing increase in the volume of urine that is polyuria. Due to increase in water loss from the body and hyperosmolarity of blood due to increased blood glucose concentration water starts moving out of cells. Now this when happens in osmoreceptors thirst centers are activated causing increase in the intake of water that is polydipsia. So till now we discussed physiological basis of certain signs and symptoms of diabetes mellitus that is fasting and post-prandial hyperglycemia, glucose urea, polyuria and polydipsia. Okay let's move further now. We know there also occurs polytagia in diabetes that is excessively eating in diabetes mellitus occurs. Why? Well, hypothalamus has two centers which regulate feeding behavior, satiety center and feeding center. The neurons of satiety center are glucose sensitive and are dependent on insulin for the utilization of glucose. Yeah this is an exception because neurons do not depend on insulin for glucose utilization. So normally when the blood glucose concentration is high as in post-prandial state satiety center neurons are active and inhibit feeding center causing decrease in feeding. However, same does not happen in diabetes because when insulin is deficient the satiety center neurons are not able to utilize glucose and become inactive that they do not inhibit feeding center. Since feeding center is not inhibited the person feel hungry and eats often that is polypagiacus. Now one thing you remember that despite eating more the body is not able to utilize the glucose as fuel that's why diabetes is basically a kind of starvation occurring despite presence of lots of fuel that is in the midst of plenty. Anyways so what happens when body is not utilizing glucose other fuels are rotten. Remember that insulin spares the use of other fuels in fed state right? So in insulin deficiency lipolysis starts in adipose tissue causing release of pre-patiacids in circulation. Thus in diabetes blood pre-patiacid concentration increases, proteolysis also starts. So with increased lipolysis and proteolysis there is weight loss. The pre-patiacids enter liver and undergo beta oxidation leading ultimately to formation of acetyl coenzyme A. This formed acetyl coenzyme A has two pates one either it enters into Krebs cycle and is oxidized to carbon dioxide or second it enters a ketogenesis pathway leading to formation of ketone bodies. When more and more lipolysis occurs as occurs in insulin deficient state more and more acetyl coenzyme A is formed and hence more ketone bodies are formed. Moreover in diabetes most of the acetyl coenzyme A is channeled away from Krebs cycle and is utilized for production of ketone bodies. Some of the ketone bodies are utilized as fuel however when insulin levels are very low or virtually absent as seen in type 1 diabetes mellitus rate of production of ketone bodies is so high compared to the rate of utilization that it decreases blood pH since ketone bodies are acidic. Acid causes metabolic acidosis also known as keto acidosis since ketone bodies are a cause of this metabolic acidosis right. These ketone bodies are also excreted in urine that is ketoneuria occurs. Now since blood pH decreases body starts compensatory mechanisms for excretion of excess acid by increasing respiratory rate and depth. This is known as cosmos breathing or air hunger because respiration is very rapid, deep and laboured as if the person is hungry for air. Some ketone bodies that is acetone is also excreted by breath causing fruity smell of breath. Now this keto acidosis is always accompanied by dehydration. See we have seen previously how diabetes is causing loss of lot of body water. Generally ketone acidosis occurs when insulin levels are very low. In these cases blood glucose concentration is too high causing too much glucoseuria and hence polyuria. So due to dehydration body starts compensatory mechanisms for restoring blood volume. See hypovolemia leads to decreased inner blood flow and hence GFR causing increased tubular normal feedback and hence activation of renin angiotensin aldosterone system. Thus causing hyperaldosteronism. Since function of aldosterone is absorption of sodium and excretion of potassium it leads to increased potassium loss from the body. Now here is a paradox that despite potassium loss from the body we check plasma potassium concentration that may appear to be normal why? First when acidosis occurs what happens is hydrogen ions start entering the cells and this is accompanied by movement of potassium out of the cells thus giving false information about plasma potassium levels. So that was about keto acidosis. Now in type 2 diabetes malitis keto acidosis is not that common since insulin receptor defect starts slowly that is some actions of insulin are preserved. So lipolysis and proteolysis are not that severe thus weight loss is also not that severe. Also since lipolysis is not that much formation of ketone bodies is also less. In contrast another problem may occur in type 2 diabetes that is hyperglycemic hyperosmolar state. In this also there is hyperglycemia causing high serum osmolarity this causes glucoseuria and polyuria and hence depletion of water however keto acidosis is not present. So in summary the clinical features of diabetes are hyperglycemia both fasting and post-prandial glucoseuria, polyuria, polygypsia, polyphagia then rise in free fatty acids concentration in blood, weight loss in type 1 diabetes malitis while in type 2 diabetes malitis there may be normal weight or even weight may be increased since that is a cause of insulin resistance. Now in extreme condition keto acidosis can occur with cosmos breathing or hyperglycemic hyperosmolar state can occur then type 2 diabetes malitis then dehydration and depletion of potassium.