hello everybody and welcome to pathophysiology alterations in self functions here are your out objectives outcomes and your outline and before we begin talking about the abnormalities or alterations that occur in cell functioning we want to take a side trip and re-review the metabolic pathway the normal actions of the cell so if you need to pause the recording and get the metabolic pathway concept map now imagine that you have a pie in front of you and that you then eat a slice of the pie what's going to happen to the glucose in your bloodstream and if you thought to yourself well i'm going to have a transient increase in my blood glucose level you'd be correct transient increase in glucose will be known as transient and hyperglycemia whether permanent transient will stimulate the release of the release of insulin hormone from the pancreatic beta cells so what does insulin do well insulin is a key that unlocks the cell and allows glucose to enter the cell so this is where we are right here is that glucose enters the cell and once glucose is entered into the cell then the cell will break that glucose down in a bunch of steps known as glycolysis now after glycolysis occurs then pyruvate two molecules of pyruvate or pyruvic acid is formed as well as nadh two molecules of nadh and then two molecules of atp and we know that atp is essentially the energy or what i call the gasoline that keeps this engine running keeps the body engine running now when there is oxygen present because that's normal when oxygen is present those pyruvate molecules then move into the mitochondria and the krebs cycle begins and yes there's a bunch of chemicals and stuff that are involved in the krebs cycle but the net process of the krebs cycle gives us a gain of eight more nadh molecules and two more ad atp molecules now with the addition of all of this nadh the nadh is another energy or power pack that is like an electric switch that allows the electron transport chain to work or to function and i think of the elextron transport chain as kind of like an assembly line in a factory so nadh turns on the switch to the conveyor belt that allows the factory to then begin making a lot more atp and in fact with the electron transport chain we have 34 more molecules of atp that are produced giving us a total of 38 molecules of atp and so this is very important for you to understand that essentially the cell is busy busy all the time manufacturing atp or the energy packs that are responsible for working all of the different metabolic things in the body and so when we talk about disorders and diseases that cause cellular level disruption we are really talking about the fact that the cell is unable to make enough atp so that the body cannot do and the cell cannot do its job now you might think okay well so what but put a name to that cell what if i told you that with some kind of illness the heart cell is now disrupted and unable to make enough atp to make the heart work so maybe that will bring a little bit more of a criticalness to your mind that you know what we need ourselves to function and work and do the jobs that they're supposed to now some of the causes of cellular intracellular problems can occur with hypoxia nutritional problems electrolytes or other solute problems acid-base imbalances and fluid distribution and so notice that these little lightning bolts are on that concept map so we can show you where in that concept map will a disruption occur when these items occur so let's look first at hypoxia and we want to define what hypoxia is because again medical terminology is such an important aspect in this course for you to understand the language what is hypoxia well it means it's a decrease in oxygen at the cellular cellular level don't get that confused with hypoxemia which simply means that there's less oxygen in the blood hypoxia decrease oxygen at the cellular level and pretty much in most of this course we do talk about that there's always a spectrum from a little bit of cellular hypoxia to a lot of cellular hypoxia but what happens when hypoxia occur if there is hypoxia in other words whenever there is no oxygen available at the cellular level then this whole piece that's right down here can't occur the only thing that the cell can do without oxygen is perform glycolysis glycolysis and notice that what is formed with glycolysis these were the three items that were formed when glycolysis occurs again understand the terms aerobic means with oxygen so with oxygen the cell can do all of these things but anaerobic means the cell can only produce or only perform glycolysis now it's a good thing that the cell can do glycolysis because we do net two molecules of atp but if i said to you i need you to drive 700 miles and i'm only going to give you two gallons of gas what would you tell me that was crazy there's no way that that is not enough gasoline and it is not enough atp from glycolysis to man or make that machine function the cell cannot work very well with only two molecules of atp so the negative side is because there's not enough atp but also if you go back to your map you'll see that what happens with glycolysis is that pyruvate or pyruvic acid is going to accumulate and if all the cell does is glycolysis over and over and over and over and that pyruvic acid is not kind of shifted into the krebs cycle then a lot of pyruvic acid is going to accumulate and this is going to cause acidosis now we're going to take a side trip to ensure that we're all on the same page of what we mean by acidosis and so when we talk about ph and whether a substance is acidotic and versus alkalotic we know that there is a ph range from 0 to 14 with zero being very acidotic and 14 being very alkalotic so you would think that the ph in our body would be somewhere smack dab in the middle at 7. well probably you know that the normal body of ph number is between 7.35 to 45 which means it's slightly tipped in the alkalotic zone well why would that be well because every cellular metabolism process really results in acids being formed and so it's kind of like an extra added insurance where we're slightly tipped in the alkalotic range now notice that the ph of 7.34 to 45 is the normal range and that you need to have this range memorized hopefully that's easy you already knew that number you're ahead of the game so let's go back to what we were talking about and that is hypoxity and it's hypoxia and it's with results on cellular metabolism we know that with hypoxia that we are the cell is only going to be able to do glycolysis and therefore a lot of pyruvic acid is going to accumulate and therefore the ph will be tipped down into acidosis and think back to basic concepts that we've already addressed and that is that acidosis or an a ph that's in the acidotic range is not the best environment for ourselves to work in and they're not going to be happy about living and working in an acidotic environment here's the other problem or the other sequela or consequence of two little atp what is most of the atp used for the atp that is produced by the cell is mostly used to work or man the sodium and potassium pump and the sodium and potassium pump is used because sodium is very sneaky and it wants to constantly go into the cell and the cell doesn't want that much sodium in there so it kind of shifts it out and so atp the majority of it is used to push that sodium back out of the cell and to bring in potassium and the reason why the sodium and potassium pump is so important is it ensures that the normal electrical cell membrane remains in its zone remains where it should be now if you think about the resting membrane potential in other words what is the electrical cell membrane status that helps the cell go to work right what is it is it normally negative or positive and hopefully you said to yourself well of course it's normally negative and what will happen without enough atp is the sodium and potassium pump gets whack-a-doodle and therefore there is a non-normal resting membrane potential that is present and therefore the cell will not work as well as it should now we're going to move on to the next problem that can occur and that's nutritional alterations there are two important categories of nutrition that we're going to address in this course and that is having enough glucose and having enough vitamins we think of glucose as being the major substance you've already talked about the fact that atp is made when glucose is broken down so it is the most important substance that the cell needs to do its job in making atps but the vitamins are also very important and we know that nadh was mentioned as being like the light switch that turns on the electron transport chain and so we know that n the n in nadh is niacin or vitamin b3 so when we don't have enough of the vitamins then problems can occur too but let's first talk about the most important substance and that's glucose and we're going to go back to that imaginary pie that's in front of us and we know that if we eat a slice of that pie our blood glucose level is going to go up in a transient state of hyperglycemia hyperglycemia will trigger pancreas to make and secrete insulin insulin is that key that unlocks the cell wall or membrane and allows glucose to enter now if we decide to eat the entire pie instead of just a slice the cells are still not going to need more glucose and they are not little piggies and they don't take more glucose than what's needed which means all of that excess glucose that we've eaten because we ate the whole pie is going to be circulating around and insulin is also responsible for directing that excess glucose to be stored and the excess glucose is stored as glycogen in the liver and the production or the making or forming of glycogen is called glycogenesis glycogenesis means creation creation of glycogen now these are known as the regulatory processes that insulin is responsible in other words the building up because the regulatory process of insulin is to allow glucose to enter the cell and make lots of atp and also to create stored glucose within the form of glycogen in a process of glycogenesis now let's talk about a scenario where you got up today and you were busy got up late and so you decided not to eat breakfast and you then ran to wherever your workplace that means that your body is moving but there is no glucose that's available to ensure that your cells are doing their job and so when there is not enough glucose that's available then you're going to enter a state of hypoglycemia your blood sugar will become a little bit low when hypoglycemia occurs then the body does what's known as secretion of the counter regulatory hormones in other words hypoglycemia stimulates the release of four counter regulatory hormones these are also known as the stress hormones because your body has to do a lot of work all the time even when you're sleeping atp has got to be made and so it is very stressful when there is not an energy source such as glucose so the counter regulatory hormones consist of epinephrine cortisol notice that epinephrine is from the adrenal gland cortisol is from the adrenal cortex epinephrine is from the adrenal medulla growth hormone as from the pituitary and then glucagon is from the pancreas and we talk about these or these hormones are referred to as the counter regulatory hormones because they do a lot of breaking down of substances now what do these counter regulatory hormones do well one of their jobs is to send a signal or an alarm in these days we talk about that as being hangry that's the individual that's a little irritable they may be sweaty they may be gripey but they're definitely hungry and these are hormones counter-regulatory hormones are sent to send a signal for you to eat if you ignore the signal and you don't eat then the next step in a back-up plan of the regulatory hormone glucagon put a circle around that students always forget glucagon's job but glucagon glucagon is stimulates the conversion of stored glycogen to glucose so that's why we have that glycogen that's there it is our stored glucose now this process the breakdown of glycogen to allow for glucose to be re-released is known as glycogenolis and of course if you're from texas is lactogenolasis and when glycogen is broken down then this results in a higher blood sugar and then the hypoglycemia will be corrected now are these processes the counter regulatory processes are they abnormal and the answer is no they're there for a reason to kind of provide that backup plan unless you haven't eaten because of course you know even when you're sleeping your heart's gotta beat your lungs gotta move your brains gotta do its functions and so atp and that energy from glucose is needed at all times now let's say that glucose is unavailable or it can't get into the cell and participate then glycogen eliases if it's exhausted a person's store of glycogen let me explain what i mean by this every one of us can store glycogen but glycogen is like a gas tank it the liver will only store so much of it and then there is some of it that will then be if there's still excess glucose then it will be shoved into fats and so whenever there is not a ready supply of glucose and then the glycogen stores as the counter regulatory process of glucagon has gotten rid of exhausted or utilized all of the glycogen stores that were available then what happens next is fats and protein may be broken down and when fats and protein are utilized for our energy source this is known as gluconeogenesis in other words the creation of energy from an alternate source and so that is the source of fats and proteins so when glucose is not available then the body must revert to other sources of energy and that's fats and proteins now again this is a good thing because we know that these alternate energy sources of fats and proteins provide the energy that our body needs but the bo the problem is is the breakdown byproduct of fats and protein is known as ketones now ketones is kind of a nickname or a short name their real name is keto acids and again if we are doing a lot of gluconeogenesis breaking down a lot of fat and protein then you're going to make a lot more keto acids and of course what can occur is the ph can dip down and then your patient will go into a state of acidosis the other sequela of gluconeogenesis and the use of proteins and fats is that the brain cannot use keto acids the brain has to have glucose for energy and the brain is so efficient in using glucose the brain doesn't need insulin to get its glucose most brain cells can just suck that glucose right out of the blood the problem is is that with acidosis then every cell is going to have a problem functioning so there is a clinical note about this that whenever individuals come in and they're confused or they're fuzzy or they're dull witted the nurse is always going to a check for the blood glucose level because the brain is so reliant on glucose for energy it cannot use keto acid so or ketones so here we go our summary where we are so far is glycogenolysis and gluconeogenesis are considered to be normal counter regulatory processes and they are triggered or they kind of begin whenever the counter-regulatory hormones are released counter-retort counter-regulatory hormones are released when hypoglycemia is present now let's talk about the abnormal issues that can arise in other words disease processes that can occur that really interfere with the body's efficiency in using these backup plans for energy and one of those is glycogen storage disease now there's quite a few glycogen storage diseases and all of them have two considerations or or two problems they either have one of two problems they either have and cause an abnormality in glycogenesis that is the process of creating and storing glycogen or they have a problem in the ability to break down the glycogen the glycogenolysis process and as i said there are 12 glycogen storage diseases and we're going to talk about one of them specifically and that's mccartel's disease which is probably one of the best glycogen storage diseases to have if you have to have one now what is mccartney's disease well it's an autosomal recessive disease so therefore it's transmitted in genetic single gene disorder in which the normal ability to break down muscle glycogen is diminished so what this means is is that yes their liver is the major storage facility for glycogen but your muscles your muscles also have the ability to store some glycogen and the cardinals disease is very specific in that you cannot break down that muscle glycogen so in other words an individual who has mcardle's disease if they're running from a bear or they're running a marathon in other words they're doing a lot of strenuous physical activity then they could experience weakness and cramps during the exercise because they lack the ability to get more glucose from that muscle glycogen there is also another glucose disease and that is type 1 diabetes mellitus now i understand that diabetes is kind of um very common or somewhat common and it's mentioned in the news but you must be aware that we are talking very specifically about type 1 diabetes and we'll go into diabetes in more day detail but for right now we're just going to scratch the surface of what diabetes mellitus is diabetes mellitus occurs when an individual does not make any insulin as in no insulin and without insulin blood glucose levels will increase in other words as we talked about this course we're going to say black and white scenario yesterday your patient was producing insulin today your patient has diabetes mellitus type 1 and they're not producing any insulin so when they eat their breakfast their blood sugar is going to increase and there's no insulin so the blood sugar does not temporarily increase it stays elevated they have a chronic constant hyperglycemia then they eat lunch they have even greater blood glucose level and then they eat dinner and they have a greater blood glucose level and on and on and on because without insulin glucose is not able to get into the cell and the cells are going yo where's the glucose here for me to make atp and because there is no glucose in the cell because there is no insulin then the individual cells all of the cells will have to revert to another or the alternate energy source which happens to be fats or proteins so the individual without insulin and without the ability to get glucose and to the cell will have markedly elevated blood glucose and sustained gluconeogenesis which is why the type 1 diabetic in other words the individual that is that is newly diagnosed or newly has no insulin can be quite thin because of that breakdown of fat and muscle because of sustained gluconeogenesis now what is going to happen as a sequela are a result of all of this gluconeogenesis well we know that keto acids are produced and they're going to provide some energy but their problem is is sustained gluconeogenesis will cause ketone over accumulation and the fancy term for ketone accumulation in the blood is hyperketonemia now how do you the nurse know or how can you identify that hyperketonemia is present well of course if the person is in the hospital and they have a blood test done you're gonna see high serum ketones or hyperketonemia on the lab values but they and they will also have a blood test to measure the ph of their blood and they will see that the ph is decreased or low and then if it's a result of ketones we will specifically call it ketoacidosis because the ph decrease is a result of ketoacid accumulation the urine can be tested and there will be ketonuria so this means that ketones will spill into the urine and then they will have what's known as acetone breath so again this is kind of the body's way to shove some of that acid and get rid of it out of the body through the respiratory tract acetone breath smells like an individual who is chewing some kind of sweet gum such as juicy fruit so chew a pack or chew a few sticks of juicy fruit and then breathe on a family member and that's acetone breath now let's talk about the other disorders or the other things that can cause metabolic pathway disruptions and we've already talked about glucose but we have mentioned in already previously mentioned that the vitamins are very very important for to ensure that the metabolic pathway is manned you can see again that niacin or b3 is a key ingredient in nadh and then there's other places where other vitamins are very important and so we're going to kind of go through the ones that you need to know now vitamin deficiencies don't occur very often in countries where there is an adequate food source i mean if you look at a candy bar and it's vitamin fortamide fortified so in the u.s for the most part vitamin deficiencies don't usually occur and as a nurse vitamin deficiencies are probably most often seen in individuals who are alcoholic in other words an individual who doesn't eat well and just drinks their meals with alcohol so if you want uh to team up with the chemist chemist try and and make vitamin fortified alcohol you make a million bucks and then you can go to nursing school for the fun of it so your alcoholic who has a very poor diet is unable to get usually iron and is so they're usually iron deficient and they usually are not able to get their b vitamins such as thiamin and niacin and the others now if an individual has iron deficiency for whatever reason of course we were using alcohol individual as our example they can develop an iron deficiency anemia because iron is very important in the formation of red blood cells and again if your individual if you have a patient who is diagnosed with anemia what signs and symptoms might you think that they have and of course we know that they have they will show signs and symptoms of weakness shortness of breath and fatigue another vitamin deficiency that is that can occur is that of thiamin now thiamin is a very important vitamin for the proper functioning of neurologic cells thiamine is also known as b1 and when individuals have a vitamin b1 or thiamin deficiency the illness is called beriberi and the signs and symptoms are usually show up as neurologic problems now because it's not often in the united states that we see individuals with beriberi but we do see some individuals who have a history of alcoholism that will come in with a thiamin deficiency that is specifically related to alcoholism and when the thiamin deficiency is specifically re related to thy to alcoholism then they change the name of the problem and it's known as wernicke corsicos syndrome so again this is a problem that occurs when your alcoholic patient is vitamin deficiency specifically thiamin deficient what signs and symptoms will you expect to see in an individual with wenaki korsakov syndrome well they will have memory loss they will have ataxia which is the fancy word for staggering uncoordinated gait and they can have eye movement issue this is kind of your pictorial reminder for the signs and symptoms of wernicke corsicoff in addition uh thiamin deficiencies and or b12 deficiencies can also cause paresthesia now paresthesia is noted as pins and needles so if you sit while you're listening to this recording if you put your foot underneath your booty and you sit on it for long enough and then you put your foot back down you'll get that kind of pins and needles feeling that prickly kind of feeling and that's what's known as paresthesia so paresthesias can occur with either thiamine or b12 deficiency so that's how important your vitamins are to the pathway now let's talk about some other items that can cause vitamin deficiencies there are certain drugs not just street drugs or recreational drugs but even some of this as some prescription drugs such as birth control pills these drugs any drug can upset or interfere with vitamin absorption so some individuals can be vitamin deficient from these problems those of us that like our caffeine my diet coke is a constant companion the diet coke or a can and caffeine can interfere with vitamin absorption from the foods that we eat and then there are some poisons such as cyanide that can interfere in the metabolic pathway now you might be thinking cyanide where the heck did this come from and why are you mentioning it well cyanide is actually a not uncommon problem in individuals with metabolic problems because cyanide is a chemical that is found in quite a few different substances you can see the list here it's found in some drugs and it is found in insecticides and individuals can buy these items and then it's kind of something that's used to kill somebody you don't like um i've usually just about on a yearly basis or maybe every few years you'll read about someone that has been feeding their loved ones cyanide they put it in sugar and then that individual puts the cyanide lace sugar in their coffee or tea or wherever and then they slowly over time develop cyanide poisoning and it is considered to be a bioterrorism drug because the signs and symptoms are kind of vague as the individual goes along and they can include a range from headache to death so i'm not going to ask you these specific signs and symptoms so how is it that cyanide prevents or disrupts the metabolic pathway well what happens with cyanide is it inhibits inhibits cytochrome oxidase so when you look on your concept map you can see that cytochrome oxidase is very important in the electron transport chain so in the electron transport chain if it doesn't work then you're not going to make or your patient's not going to make that big mother load of atp so they're not going to be able to make enough atp and so therefore your cell is not going to make enough atp to do its functions that it needs to do i'm kind of summarized the list of the g words these are all the g words that you need to know glucose glycolysis and so on and so on if you have any doubts as to their definition you can either email your instruction or look them up if you have any questions be sure again to email your instructor and then you can stop the recording and we will move to another recording for part two