0:00 Hello, in this video we're going to look at ethanol physiology. 0:08 So the physiology of alcohol, how we metabolize it, how we absorb it, etc. 0:13 So we begin with the liver. 0:14 Here is the liver. 0:15 The liver has a portal vein. 0:17 The portal vein essentially is what drains all the GIT stuff into. 0:23 So the GIT veins drains into the portal vein and the portal vein drains into 0:28 the liver. 0:28 And here we have the liver cells, also known as hepatocytes. 0:32 Here is the liver sinusoid. 0:35 And within the area there are also liver macrophages called coopfic cells. 0:40 There are also hepatic stelate cells here, which are normally at rest, they 0:44 stay dormant. 0:46 They're not really active. 0:48 Anyway, that was the liver. 0:52 Here are your intestinal cells, intestinal cells of the stomach and the small 0:57 intestine 0:58 for example. 0:59 And here is the lumen. 1:01 So on these intestinal cells, sorry, there are mucus, and mucus is a barrier. 1:10 It helps to barrier from microbes and stuff like that. 1:14 Now normally reciting on the mucus throughout the gut, throughout our 1:19 gastrointestinal tract, 1:20 there are commensal bacteria, mainly gram-negative bacteria. 1:24 Now commensal bacteria are just bacteria that live there in unison with the 1:30 organism, which 1:30 is us in this case. 1:33 Now ethanol has an impact on gram-negative bacteria, and we will see what 1:40 happens. 1:41 So ethanol, which is alcohol, will be in the lumen when we drink it, right? 1:46 And now chronic alcohol consumption, it causes a few local changes in the 1:51 gastrointestinal 1:51 tract. 1:52 Basically, it actually increases gut permeability and promotes bacterial growth 1:56 , which may lead 1:57 to increase in circulatory lipopolysaccharide. 2:02 Now lipopolysaccharide is an antigen found on these bacteria normally. 2:10 So when you have a lot of growth of these bacteria due to alcohol and the 2:15 increase in 2:16 gut permeability, the lipopolysaccharide of the bacteria can get into 2:21 circulation. 2:21 That's essentially the overall picture. 2:25 So that was the lipopolysaccharide story for now, and we'll get back to it. 2:29 But first, let's go back to the gastrointestinal tract. 2:34 Ethanol, of course, is absorbed in the gastrointestinal tract, mainly in the 2:40 stomach and the small 2:42 intestine. 2:43 Okay, so let us now look at the effects lipopolysaccharide LPS has on our body. 2:49 So LPS travels to the liver. 2:52 Here LPS lipopolysaccharide is recognized by cupfa cells in the liver through 2:58 toluic 2:58 receptors, which are immune cell receptors essentially. 3:02 When cupfa cells recognizes the lipopolysaccharide, it begins to creating cytok 3:07 ines, such as 3:08 TNF-alpha, interleukin-1, interleukin-6, and interleukin-12. 3:14 These cytokines have many effects. 3:17 One of which is recruiting more white blood cells into the area, such as mac 3:25 rophages. 3:26 And thus, you know, attracting macrophages, it promotes an inflammatory 3:31 response. 3:31 The cytokines also stimulate hepatic stelate cells to become activated and to 3:36 secrete interleukin-8, 3:40 an effective chemotactic agent for recruiting, circulating neutrophils, which 3:44 will further 3:45 enhance the inflammatory response. 3:49 So infiltration of neutrophils and macrophages together with hepatic stelate 3:54 cell activation 3:55 leads to inflammation as well as fibrosis. 4:00 The stelate cells, when activated, it actually becomes myofibrosides and begins 4:06 producing 4:07 a lot of collagen, which is the culprit for fibrosis. 4:15 So we just saw the effects lipopolysaccharide has on the body and how 4:20 inflammation leads 4:21 to fibrosis. 4:23 Now let's go to ethanol, which was absorbed into circulation. 4:27 Let us see the biochemical effects ethanol has on the liver. 4:31 So ethanol is absorbed in the portal vein and it travels to the liver, like the 4:37 lipopolysaccharide. 4:39 Let us zoom into one of these hepatic cells and see the metabolism that occurs 4:45 for liver, 4:46 for alcohol. 4:47 So excess consumption of ethanol, we have ethanol moving into the liver cells. 4:52 There are several pathways of ethanol metabolism. 4:57 So we have excess consumption of ethanol. 5:00 Ethanol moves from the outside to the inside of the liver cell. 5:04 Ethanol gets metabolized, converted into acetyl aldehyde and there are two main 5:10 pathways. 5:10 The first one and the main one is done by the enzyme alcohol dehydrogenase, ADH 5:19 . 5:20 And in this reaction, NAD is reduced to NADH. 5:26 The second pathway is through the cytochrome pathway. 5:31 So ethanol is still converted to acetyl aldehyde, but this reaction results in 5:37 the production 5:37 of reactive oxygen species, ROS. 5:42 So therefore, the liver usually uses the alcohol dehydrogenase pathway, 75%, 5:47 compared to the 5:48 cytochrome pathway, 25%. 5:51 Because if we have too much acetyl aldehyde and reactive oxygen species, this 5:58 stuff damages 5:59 our body. 6:00 So for example, it can cause formation of DNA adapts, resulting in mutations, 6:05 which can 6:06 result in some problems. 6:11 But of course, if we have so much ethanol, you can imagine what happens, we 6:16 start using 6:17 the cytochrome pathway, and so we produce a lot of reactive oxygen species. 6:24 Anyway, when we have a lot of acetyl aldehyde, this can also be converted to 6:29 acetate through 6:30 the enzyme acetyl aldehyde dehydrogenase. 6:34 In this reaction, NAD, again, is reduced to NADH. 6:40 So we are producing a lot of NADH when we drink a lot of ethanol. 6:47 Just keep that in mind. 6:48 We have a lot of NADH. 6:51 So acetate can be converted to acyl coa. 6:55 Acyl coa is a main precursor to fatty acid synthesis. 7:00 Now, fatty acid synthesis is actually stimulated when we have a lot of NADH, 7:08 because NADH is 7:10 used in the synthesis of fatty acids. 7:17 So NADH is oxidized to NAD. 7:20 So all the hydrogens are being used to make up the fatty acids. 7:26 So fatty acids, a lot of fatty acids, are being made. 7:29 And also, the fatty acids are being packaged up to triglycerides, triacylglycer 7:34 ides. 7:34 And so NADH also stimulates this reaction. 7:40 When we have a lot of NADH, which we see in excessive alcohol intake, a lot of 7:47 NADH thus 7:48 inhibits fatty acid breakdown. 7:52 So it inhibits triglyceride breakdown to fatty acids. 7:56 And it also inhibits fatty acid breakdown to acyl coa, it inhibits beta 8:03 oxidation. 8:04 Because we don't need any more NADH when we have so much, so it inhibits this 8:11 reaction. 8:13 So I hope that all made sense. 8:14 But in summary, this is the main concept we have to take out of excessive 8:20 alcohol intake. 8:21 When we have excessive alcohol intake, this results in an increase in fatty 8:26 acid synthesis, 8:27 but a decrease in fatty acid oxidation, so fatty acid breakdown. 8:33 When this happens, it basically means that we have a lot of fat in the liver. 8:37 And so this results in steatosis. 8:41 So we have two main things happening, or three. 8:45 We have inflammation, we have fibrosis, and we have steatosis as a result of 8:50 excessive 8:51 alcohol intake. 8:53 And this all results in liver cirrhosis. 8:59 I wrote here liver fibrosis, but it should be liver cirrhosis. 9:02 But same concept. 9:06 Just to finish off this metabolic pathway, when we have glucose, right, so 9:12 glucose gets 9:13 transported into liver cells through the glucose through glycolysis to make py 9:19 ruvate, pyruvate 9:20 or then goes through other pathways. 9:23 But glycolysis actually produces NADH. 9:28 But when we drink a lot of ethanol, we also produce a lot of NADH, right? 9:33 So when we have excessive ethanol consumption, we actually inhibit glycolysis. 9:40 So we inhibit glucose breakdown. 9:43 Similarly, a lot of NADH will inhibit pyruvate conversion to acetyl-CoA. 9:53 So thus, we can cause hypoglycemia, but actually, we don't. 10:01 Excessive ethanol intake causes the person not to be hungry, thus can lead to 10:08 hypoglycemia. 10:10 Glycogen stores are also not being broken down, thus leading to hypoglycemia. 10:16 Just to complete this whole diagram now, excessive ethanol intake not only 10:22 affects the liver, 10:23 but also affects our neurological system. 10:26 So for example, excessive ethanol intake can lead to vitamin B1 deficiency. 10:33 The vitamin B1 is known as thiamine deficiency. 10:36 And thiamine is very important in our, you know, is very important for our body 10:43 because 10:44 thiamine is responsible for a lot of metabolic pathways. 10:48 So thiamine deficiency results in three things. 10:53 So thiamine deficiency can result in a condition known as berry berry. 10:58 Wernicke's enthalopathy, basically neurological pathology, and also course 11:06 cough psychosis. 11:08 And this is essentially memory loss. 11:11 So I hope you enjoyed this video on the physiology of alcohol or alcohol 11:15 physiology. 11:16 Thank you for watching. 11:17 Bye. 11:18 You
