Transcript for:
Shock: Cardiovascular Collapse

now today the topic of discussion is shock it is not emotional shock it is cardiovascular shock it's a clinical pathological condition in which cardiovascular system collapses and there is widespread hypoxia to multiple tissues in the body is that right and this condition has very high mortality and if young doctors have good understanding of this topic right they can save more lives so to start the topic with shock first of all we'll talk about the very basic about the cardiovascular system let's suppose this is a cardiovascular system of a healthy person and if this is a cardiovascular system of a healthy person i want to know that what is the cardiac output in a healthy person when he is resting yes mr israel five leaders five letters so cardiac output is excellent five liters per minute in a healthy person who is resting and then another question what is the okay ms yara will tell us what is the volume of blood in a normal healthy person you mean cardiac output and blood volume are equal yes okay i like your confidence so ms jarrah is telling that volume of blood is five liter in a healthy person approximately right so you can see it that your circulatory system has five liter blood and the same amount is passing of the cardiac output every minute now another question is that what is the capacity of cardiovascular system in a normal person yes please capacity of cardiovascular system i am not asking about volume what is the capacity of cardiovascular system it is five liters because in a normal healthy person cardiovascular system is 100 full you can puncture any capillary anywhere or any vessel anywhere blood will come out it means in a normal person the blood volume and blood capacity and capacity of the circulatory system that is equal right it means that in normal person cardiovascular system is 100 full of blood is that right or we can say that in a normal healthy person the volume of the blood and the capacity of the blood they are not having any disparity is that right because uh if they are equal it means all the cardiovascular system will be full so whenever left heart will push the blood to the circulatory system of course venous blood will return back to the right heart is that right now what can produce shock there's so many reasons that different patients undergo shock for different reasons one of the reasons is that problem is disparity between the volume and the capacity there is difference between the or disparity between the volume and the capacity for example if some patient has lost some blood volume let's suppose in this patient there is bleeding or due to any reason he has lost blood out of cardiovascular system right if he has lost the blood now his volume will not be five liter let's suppose volume is 3 liters let's suppose that volume is 3 liters now you see capacity is 5 liter volume is 3 liters so circulatory system is overfilled or under felt it is under filled right and if circulatory system is under filled it cannot mean effective pressures within the circulatory system and if cannot maintain the effective pressures do you think the left heart will pump to the circulatory system if it is under filled attention please will the blood easily return to the heart no when circulating system is not properly filled right for example on the patient my heart pump the blood to the periphery blood will go to the periphery but because volume is less and capacity is more so pressure and circulating system are so low that venous return to heart is less and if volume is less then venous return to the heart is less and cardiac output will drop and eventually if the serious the situation become very serious cardiovascular system will collapse and functioning and cardiovascular system is not functioning well it cannot maintain a circulated system it cannot provide the tissues with the proper oxygen supply and other nutrients and it cannot remove the waste products is that right and wide spread hypoxia will start and will say patient is going to cardiovascular shock as we defined earlier what is shock it is a clinical pathological condition in which in which there is circulatory collapse and that circulatory collapse is resulting in widespread hypoxia and widespread uh deficiency of blood perfusion all over the body is that right now i told you that different patients may have different reasons of having the shock this is one patient we talk about that he lost the volume and because he lost the volume and loss of the volume produced disparity between the volume and the capacity and that produced the reduced venous return and reduce cardiac filling and reduce cardiac output and that will that is taking such patients to the shock this type of shock is called hyper volumic shock limit shock right now we come to another patient talk about another patient this is our second patient let's suppose this patient has normal volume volume is 5 liter normal capacity that capacity is also five letters right it means if volume and capacity disparity is not there they are properly matching volume and capacity but this person has a real trouble with the heart for example he has massive myocardial infarction and due to massive myocardial infarction heart cannot work as a pump now listen if volume and capacity are matching well circulated system has effective circulatory pressures but if your pump fail do you think you can maintain the circulatory perfusion to the different tissues can you maintain the supply of oxygen and other nutrients to the tissues no so it's not enough to have volume and capacity matching of course we need heart also to maintaining good pumping action right in some patients the primary cause of shock is that your heart is feeling as a pump and if there's dangerous reduction and pump function of the heart of course cardiovascular system will collapse and in spite of normal volume and capacity blood will not be circulating in a proper fashion and tissues will not be provided with enough blood enough perfusion enough you can say oxygen and nutrients right and we'll see patient is again going into shock such type of patients where the real problem is with the pump action of the heart right there's pump failure the mechanism here was pump failure right and this was you can say volume failure right and first patient there was volume failure this was the first patient and second patient group of patients in second group of patient we are talking about pump failure right and when there is pump failure what is the result the cardiovascular system cannot maintain its perfume pattern to the all body tissues and patients will go into shock and this shock is called this type of shock is called yes cardiogenic shock cardio genic shocked there is cardiogenic shock now we come to two more situations think of another patient right and in this patient heart is perfectly okay problem is with the capacity due to any reason cardiovascular system capacity dangerously increases now let's suppose heart is perfectly okay the primary problem is that capacity has become supposed capacity has become 8 liters and volume is 5 liters now the volume capacity is more volume is normal it means again there is disparity between the volume and capacity and effective feeling pressures are not maintained can we maintain the venous return no because again peripheral pooling of the blood will be there now compare the case number one and case number three in case number one there was also volume and capacity this disparate difference and case number three also this volume and capacity difference but in case number one there were loss of volume in case number three there was increase in capacity but in both cases circulatory system is not properly full in both cases venous return cannot be maintained in both cases of course secondarily a cardiac output will drop is that right so this type of situation where capacity has become too large and you can say distribution of the blood in the body become pathological distribution of blood and the body becomes pathological because blood is too much distributed in the peripheral tissue peripheral vasculature which is dilated too much if it is so then can you give me some example like this in which cardiovascular especially vascular system dilates too much and blood pools in the paraphrase and then venous return cannot be maintained and patient may go into shock every doctor must know the example every doctor without any exception you would like to tell me something yes madam you have any condition in which suddenly the capacity of vascular system increases dangerously and when capacity increases dangerously the normal volume is not enough to fall blood becomes pulled venous return is not maintained cardiac output drops suddenly and patient can die within short time in front of you please tell me anaphylactic shock in anaphylactic shock what really happens for example pencil in hypersensitivity or if a patient has made ige against a drug and you give that drug intravenously to the patient what will happen to the patient you know if you are allergic to some substance and you have made ige against that then what really happens these are your mast cells you know mass cells are well present around the vascular system write down mast cells are well concentrated even though they are present all over the body even though mass cells are present all over the body but they are specially concentrated around the blood vessels under the skin and mucosal linings and mucosal lining now what really happens that mast cells are having ige antibodies right now let's suppose in this patient this patient has ige antibodies against a venom and if that particular venom enter or that particular substance against which this person has made ige if that substance enter in the body look here that substance will activate the ig e and ige will stimulate the mast cells and mass cell will release many substances and one of those substances is yes what is that histamine and when massive amounts of now listen carefully let's suppose if i have made ige against a particular drug substance and unfortunately you don't do logic test and skin testing you directly infuse that drug into my blood that drug will go bind with the ige immunoglobulins present on the mast cells all over the body and all the muscle cells will release lot of substances one of them is histamine and all this histamine which is released around the blood vessels by the mast cell lead to massive dilatation and blood will be abnormally distributed in the body and will it come back no and will be in a trouble this is just one example right this is usually called enough electric shock but listen there are other examples also because it's a full group is called distributive shock district beautiful shock distribute blood distribution is abnormal the example of anaphylactic shock is just one of the examples of distributive shock anaphylactic shock is just one of the type of distributive shock in which there is again volume and capacity disparity and major reason being that capacity is dangerously increased can you tell me some other condition in which capacity is dangerously increased please tell me neurogenic shock in some conditions if sympathetic nervous system fails for example if someone wants to commit suicide and takes a high dose of sympatholytic drugs sympathetic tone is lost all the blood vessels dangerously dilate and patient will go into neurogenic shock so neurogenic shock is again a type of distributive shock is the right real mechanism is distributive problem okay tell me any other reason of where this distributive shock where cardiovascular system vessel system pathologically expands and blood is lost in the periphery and venous return cannot be maintained cardiac output cannot be maintained there is one condition which is so common so well known we have just talked about anaphylactic shock which is a type of distributive shock then we have talked about neurogenic shock which is again a type of distributed shock can you tell me some other example of distribution please please please tell me septic shock septic shock everyone should know isn't it we are becoming doctors septic shock when the there is some septicemia in your body even a lot of bacteria are there especially ground negative bacteria which release a lot of endotoxins then endotoxin induced cytokines are produced and the that produces massive visibilitation right in septic shock one of the problem is that a lot of blood vessels dilate because in septic shock we'll have a full lecture on septic shock later right i'm just introducing the types of shock we'll discuss in detail septic shock later on right now i'm just telling you what really happens in septic shock that a lot of toxins are present in the blood a lot of bacteria are present in the blood if endotoxins are there right they will damage all the endothelium and activate a lot of white cells and they'll produce a lot of cytokines and these products will produce massive arterial dilatation and endothelial injury so in septic shock all the blood vessels will dilate and there will be increased what capacity with that because endothelial leakiness is also increased in septicemia so even some volume is also lost from the blood to the interstitial area right so we can say that anaphylactic shock or there was neurogenic shock or there was yes septic shock all these are the examples of distributive shock all these are the examples of distribution distributive shock and there are more also we'll talk about that so how many mechanisms of shock now you know number one volume failure hypovolemic shock then we said that pump failure cardiogenic shock then capacity failure pathological increase in capacity and distribution failure so we call it distributive shock any other cause of shocks you can tell me okay we talk about one more patient and now you have to use all the layer of your cerebral cortex to answer this question right in this patient cardiac output is okay heart is okay heart is healthy in this patient i mean myocardial pump function is okay pump pump is capable of doing its function again in this particular patient there's no primarily pump failure because myocardium is healthy and able to pump capacity is normal volume is normal still shock occurs of course it will not fall into any of the first second and third category what could be the now mechanism we have said there are four mechanisms of shock primarily right one mechanism is volume is lost and volume capacity disparity other is capacity is gain again volume capacity disparity difference pump fail so either volume fail or pump fail or capacity fails and then one more type of patient he is in shock cardiovascular system is not working cardiovascular functions are collapsed and arterial profusion to the most of the tissues is not maintaining and patient is having widespread hypoxia and nutrient deficiency at a dangerous level but this patient and had had initially normal pump function he had normal capacity and normal volume what could be the mechanism yes yes anything comes to your mind heart failure if you put heart failure that is cardiogenic shock pump failure isn't it that will fall into this category so it is not hard failure okay i will tell you something if we really put some obstruction to the system even though pump is a pump can work volume is okay capacity is okay but lumen is obstructed in a dangerous way cardiovascular for example pulmonary artery is blocked by a very big ambulance pulmonary thromboembolism have you heard of it this is a massive embolus from deep venous thrombosis a big thrombus has embolized from the deep veins of the leg it is not a rare thing and this get right heart pump this thrombus into pulmonary artery and it blocks the big portion of pulmonary artery now harder the pump is okay volume is okay capacity is okay what do you think the tissues will be well perfused not at all there is obstruction what is there now the problem is obstruction is that right and when there is obstruction we should call this condition obstructive shock we should call this condition obstruct div shop now listen carefully these are just four basic mechanism of shock let me now repeat the basic concept what is shock shock is a clinical pathological condition in which there is in which there is cardiovascular failure this cardiovascular collapse resulting into so poor peripheral perfusion arterial profusion that even tissues are not receiving the minimum amount of nutrients and oxygen for their metabolism that means cardiovascular collapse is leading to generalized generalized hypoprotein in the body what are the four mechanisms look here again if the volume is lost or heart pump function is lost or capacity is dangerously increased and effective pressure in circulating system is lost or there's major obstruction to the cardiovascular flow system we say lumen failure what is there lumen failure lumen failure so there can be volume failure patient number one pump failure patient number two capacity failure patient number three lumen failure of cardiovascular system question number four right now we will talk about the common causes of hypovolemic shock hyperboor limit shock now what could be the common causes of this right now this is the patient in which problem is with the volume the volume of cardiovascular system is reduce volume loss volume loss from cardiovascular system is that right why the volume is dangerously reduced now the simplest cause is hemorrhage the simplest cause must be hemorrhage bleeding hemorrhage we also call it hemorrhagic shock now when we talk about loss of blood or hemorrhagic shock again the blood may be lost from the cardiovascular system but within the body or outside the body so it may be hemorrhage and hemorrhage may be external hemorrhage external hemorrhage or it may be yes internal hemorrhage hemorrhage some people call internal hemorrhage concealed hemorrhage right someone is suppose actively bleeding from the cardiovascular system but if blood is evident outside we call it external hemorrhage or if it is accumulating within our body right and it's not evident outside then we call it internal hemorrhage the example of external hemorrhage may be the classical example is simply like roadside accident right and roadside accidents someone has swear trauma or we can say simply trauma we can write it more trauma right and person is actively bleeding and you can see the blood right or another example is sometimes git bleeding which is heavy bleeding right git blading if heavy bleeding in git and person vomit out of the blood this is called hematomas right or person passing a lot of blood per rectum right if there's bleeding in lower part of the jit right and sometimes the amount of the bleeding will be so much that person may go into shock right then we can come to internal hemorrhages that sometimes bleeding is going on within our body and it is not evident outside the classical example of this is when there is rupture of ectopic pregnancy you know when ectopic pregnancy for example a lady who is having product of conception in a tube flopping tube and then it eventually ruptures she will have heavy bleeding within the peritoneal cavity right so example like this internal hematomas hemothorax hemo thorax or there may be hemoperitoneum right as i told you one of the simple example is ruptured ectopic pregnancy or someone has ruptured aortic aneurysm is that right it's an internal example of internal hemorrhage now but some people they don't lose the whole blood they just lose one of the major component of the blood and then become hypovolemic right for there are conditions in which there is loss of plasma there is loss of plasma loss of plasma can you tell me some conditions there may be massive loss of plasma out of the cardiovascular system and of course cells are left behind so there is humor concentration and hematocrit become high again i am asking you a condition in which some plasma is lost out of cardiovascular system and remaining cells in the cardiovascular system they become too much concentrated and there's a human concentration method goes up classical example is yes burns burns if the extensive burns on the body from the burnt tissues you know a lot of plasma exude out because in burnt tissue there's severe thermal injury and nearby capillaries have severe inter-endothelial gaps formation there's too much endothelial damage and people start oozing out not simple fluid but a lot of plasma outward so patient who are having extensive burns a lot of plasma fluid oozes out of cardiovascular system into burnt tissue right and effective volume has been reduced in cardiovascular system right then there is another condition i am not expecting you to know but if you know it i will be pleasantly surprised there is another condition skin condition in which there is a very swear inflammation of the skin and a lot of you can say plasma is lost into skin layers right and cardiovascular system become deficient in volume so can you tell me the condition okay before you tell me something totally and new that condition is called exfoliative exfoliative dermatitis exfoliative dermatitis right now next next thing which can be lost from cardiovascular system is look in category a we were talking about the whole blood was lost in category b we were talking about the plasma loss right in category c of hypovolemia we will be now discussing loss of fluids and electrolytes loss of fluids and left light out of circulatory system right lot of fluids and electrolyte i think the simplest examples are for example in swear diarrhea of course if person is losing too much fluid and diarrhea how do you define the idea i know everyone knows diarrhea what is how do you really medically define the idea okay how much daily fecal matter you are allowed to produce what i really mean that if fecal matter is more than that will say you have diarrhea because the fecal amount is more than that then either you can say frequency of the defecation will increase and fluidity of the content will increase so how much normally you should produce it is about usually it's around 200 ml and if it is yeah and if you're 250 ml around that if you're more than that we say you are having diarrhea is that right now anyway someone is losing too much fluid for example in cholera person is losing too much fluid and when he try to drink the water he will warm it out right even you can say diarrhea and vomiting okay diarrhea and vomiting right without fluid replacement will lead to sphere losses of volume so this may be diarrhea git losses or there may be vomiting again git losses right or polyurea hyper smaller conditions in hyper smaller conditions there's a heavy loss of volume in the urine right there may be only urea without replacement of the fluids the patient has diarrhea or he has vomiting or he has polyurea is that right and this type of situation is specially seen in diabetic ketoacidosis dka have you heard of decay diabetic ketoacidosis again we'll discuss that topic in medicine very important if you really know the the arrangements in decay and you are capable of correcting it you are capable of saving the life right so hyper smaller conditions like diabetic ketoacidosis or polyuria due to any reason and then of course if you're lost in the desert hot burning blazing sun and you are not having enough water that will lead to severe dehydration also so you can see excessive excessive yes sweating excessive sweating without fluid replacements right this can also lead to fluid and electrolyte losses right so these fluid and electrolyte losses which i have discussed here these are external losses these fluid and electrolyte losses are external losses these are the external losses then fluid and electrolyte balance or you can say fluid may be lost internally there may be internal losses internal losses are actually called third spacing internal losses that within your body fluid and electrolytes are lost rather fluid and electrolytes and massive amounts are trapped within your body and if they are trapped of course they're lost from circulatory system the classical example of this situation is ascites or bowel obstruction this may be asitis or bowel jit obstruction or uranus acute pancreatitis when pancreas becomes purely inflamed then lot of tissue around it also become inflamed and lot of fluid is in that inflamed area a lot of fluid is trapped and the some of the fluid is uh you can say accumulated into smaller sac or bigger sac is that right so in pancreatitis also lot of fluid is trapped pancreatitis of course acute pancreatitis not corona that will lead to formation of pseudocyst within abdomen have you heard of this term and such you know pancreatitis is managed on medical floors or surgical floors this is a medical condition which should be managed on surgical flows because acute pancreatitis will mix like surgical emergency so usually they get admitted into surgical site and if complete serious complications develop then you may need to do surgery right so that is why about pancreatitis acute pancreas swear acute pancreatitis you can write it down it's a medical condition which is usually managed in surgical floors right so these were some important causes of hypovolemic shock what we learned here in category a we were losing the whole blood in category b we were losing just plasma in category c just a part of a plasma fluid and electrolyte which may be lost externally or internally now we will be discussing the main causes of cardiogenic shock cardiogenic shock cardiogenic shock now as i told you in cardiogenic shock the main problem is that their heart is unable to produce enough cardiac output problem is not with the volume or the capacity now we have to see that why heart is unable to produce enough cardiac output right what could be the reason one reason could be like arrhythmias cardiogenic shock one causes and here the point which you have to remember is that arrhythmias e they are braidier than other tachyarrhythmias both can lead to cardiogenic shock i will explain how arrhythmias which may be tachy arrhythmias techie arrhythmias as well as severe breathy arrhythmias ready arrhythmias now the question is that how techy arrhythmia will lead to shock for example we talk about ventricular fibrillation first i have to make a very important concept clear when heart rate increases usually we say cardiac output is equal to heart rate into stroke volume is that right now normally when heart rate is increasing cardiac output is increasing but when heart rate goes beyond a certain limit when heart rate will start going beyond a certain limit cardiac output decreasing why because then stroke volume is dangerously going down the question is that when heart rate becomes really very high why stroke volume dangerously is reducing answer is when heart rate become very far very very fast then naturally cardiac cycle time is reduced for example if i tell you that your heart rate is 220 is that right then how your cardiac output will be less me explain for example your heart is beating at the rate of 72 beats per minute under these circumstances one cardiac cycle time is 0.8 second out of this point eight seconds point three second is for sisterly and point five second is for directly is it clear now it is when your heart rate is supposed 72 and your cardiac cycle time is 0.8 seconds now you imagine your heart rate becomes 3 times more for example your heart rate is 216. your heart rate is 216 ventricular beating is 216 it means cardiac cycle duration is one third rdx cycle duration will become one third it is no more point eight second how much it will become point two six seconds for example now you see cardiac cycle duration has been reduced significantly on at very heart rate but out of this the point which you have to remember is that major changes that systole out of 0.3 second may be now 0.2 second and directly directly which was 0.5 second maybe 0.06 seconds now what did we learn that when heart rate goes steadily increasing it is not the systolic time which rapidly reduces but really reduces its diastolic time diastolic time is the ventricular filling time diastolic time is ventricular filling time so what really happens again let me explain that in the patients when heart rate start going up right beyond a certain limit for example around 180 beats per minute directly start shrinking rapidly and directly become diastolic time becomes so less that ventricle cannot fail if ventricular filling times are dangerously reduced can we maintain the stroke volume so even if heart rate is very high stroke volume is too low and when stroke volume is too low cardiac output drops now let me give you an example that let's suppose if i say your heart rate is very fast it is 200 and stroke volume is only 10 then total cardiac output is 2 000 but normally you have 72 heart rate and about 70 mls stroke volume and it become 5000 ml or you can say 5 liter now it means person with 72 beats per minute and stroke volume of 70 is having cardiac output of 5 liter but the same person when heart rate goes very very fast right heart rate has gone very very rap fast like 200 and stroke volume has dangerously dropped from 70 to 10 then increase in the heart rate is not as much as much there's a dangerous precipitates fall in the stroke volume so in the end cardiac output is dangerously low and this person will go into cardiogenic shock so from today onward you have to remember one thing when heart rate start increasing initially heart rate is increasing but stroke volume is not significantly affected so cardiac output keep on increasing but when heart rate becomes so fast the diastolic time becomes so less that ventricular filling is dangerously impaired and stroke volume dangerously start falling then naturally it further increase in the heart rate will be associated with decreasing cardiac output not increasing cardiac output and if heart rate is really too fast then heart will not pump well and you will end up with cardiogenic shock the classical example here i would like to give is ventricular arrhythmias you know in ventricular arrhythmia what is the cardiac output answer is zero because when ventricular sorry especially ventricular i mean fibrillation corrected in case of ventricular fibrillation right in case of ventricular fibrillation electrical activity of ventricle may be 400 right per minute but heart is beating electrically so fast that mechanically hard cannot work and cardiac will drop to zero so in ventricular fibrillation patient may be pulse less and bp less so when patient becomes pulseless and bp less of course if you don't defibrillate him rapidly he's going to die so what i'm going to say that again let me repeat it that techie arrhythmias can produce cardiogenic shock but you have to remember that slight tachycardias actually increases cardiac output but when tachycardia becomes very fast and diastolic time rapidly reduces and you undergo cardiogenic shock is that clear now we come to brady arrhythmia it's easy to understand the sphere brady arrhythmia why they will take to the you can say cardiac failure or cardiogenic shock again let me repeat it the cardiac output is equal to heart rate into stroke volume is that right now cardiac output if someone has heart rate of only 10 and even if stroke volume is normal like 70 700 ml is extremely low cardiac output normally cardiac output is around 5000 so this is a and calculation which is showing that swear brady arrhythmias in spite of the fact that even if stroke volume is maintained well you will have dangerously low cardiac output and you will go into what problem hydrogenic shock so arrhythmias very severe tachyarrhythmias or very severe bloody arrhythmias both of them can precipitate cardiogenic shock by reducing the cardiac output dangerously low right then we can come to true pump failure right that in the heart problem is not with the rhythm this was cardiogenic shock due to rhythm problem now we are going to talk about cardiogenic shock which is truly due to pump failure pump failure right the classical example of this is massive myocardial infarction massive myocardial infarction massive myocardial infarction when this massive myocardial infarction let's suppose this much area of the myocardium is infected right and it is not contracting can heart maintain cardiac output because stroke volume will be dangerously low and again patient will go into cardiogenic shock right palm failure may be massive myocardial infarction sometimes from failure may be due to severe type of cardiomyopathies cardio myopathies for example dilating cardiomyopathy and dilating cardiomyopathy what really happens that myocardium is left ventricular is dangerously dilated and if left frontal is too much dilated right then it cannot maintain the cardiac output let me explain why if left ventricle is too much dilated is that right now white cardiac output cannot be maintained because the pressure which is generated pressure which is generated to push the blood out the pressure which is generated to produce a stroke volume right is equal to roughly tension by radius i have omitted some part of the equation but pressure is directly proportional to the tension in the wall the tension which is produced in the wall and the radius what really happens that in a very much dilated heart right that whatever tension heart can produce because radius is too big so it cannot produce the pressure let me tell you one simple example that let's suppose normal heart is producing pressure of 120 or pressure of 100 millimeter of mercury right and radius is 5 centimeter square right and maybe then tension is how much it is 500 units so 500 units of tension divided by 5 centimeter is 100 unit of pressure now you imagine that tension is same but it has dilated and if it has dilated now it is post 10 centimeter if it is 10 centimeter the pressure generated are very very less these pressures are not enough to maintain enough cardiac output and that will translate into what that will translate into cardiogenic shock so what i'm trying to explain here that there may be severe rhythm problems techies neosphere or body arrhythmias where both will end up into cardiogenic shock or this pump problem either there is very much dilated heart or there is a non-kinetic you can say hypokinetic heart hypokinetic heart mean heart is not contracting well for example in massive am i you will end up with the cardiogenic shock then another condition is which can lead to cardiogenic shock as sphere valvular failure so where valvular for example regurgitation sphere valvular dysfunction especially regurgitation sphere valvular dysfunction for example we talk about valvular regurgitation again one of the simple example that if there is valve become acutely regurgitant if valve becomes acutely regurgitant right cardiac output cannot be maintained let's talk about mitral valve that here is mitral valve and here are corda tendony and here are muscle papillary muscles now what really happens that if there is and suppose if there's infective endocarditis here and infective vegetation destroy the valve there will be very severe regurgitation so whenever left ventricle will contract right rather than producing stroke volume towards the aorta lot of blood will be regurgitating in reverse direction into atrium right number one number two or another example is that let's suppose the rupture of a pylori muscle in some patient with myocardial infarction a papillary muscle is also damaged there may be rupture of a poly muscle and if there is rupture of papillary muscle right then papillary muscle of course lose their function and whenever left ventricular contract it will be leading to very strong regurgitant current to the atrium so it cannot maintain its stroke volume and cardiac output and that will lead to cardiogenic shock so cardiogenic shock can be produced by very sphere valvular line like mitral valve regurgitation or aortic valve regurgitation regurgitating leans are more prone to produce cardiogenic shock than the stenotic leans then one of the very simple example cardiogenic shock when there is rupture of free wall of the left ventricle or when there is rupture of cardiac septum let's suppose here is your heart and this area is infected this area is infected of course here is your pericardium now what really happens that on third or around the third day of the myocardial infarction lot of neutrophils and macrophages are active within the infarcted tissue and sometimes this neutrophil the macrophage produce so much proteolytic and destructive enzymes that myocardial tissue may be very weak and during a strong system it may rupture and if it ruptures it will throw a lot of blood into which cavity pericardial cavity right and of course it is no more effective pump and the blood which is coming into pericardial cavity right you can say there will be hemopericardium and this pericardium when it become full it will squeeze the heart and heart will lose its function and you will go into swear cardiogenic failure is that right or yes septum and some infection septum is also involved and if septal wall ruptures whenever left ventricle will produce the tension to produce the pressure lot of you can say blood will be effort of the left ventricle will be lost as blood is moving from left to right am i clear so we can say that rupture of ventricular septum or the free wall rupture of rupture of ventricular septum or free wall that will also lead to failure of the ventricle to work right that will lead to cardiogenic shock now we come to distributive shock we have already discussed some component of distributive shock that we discussed that in distributive shock what really happens is that there is pathological and massive dilatation of vascular system and when vascular system is dilated too much right blood is pathologically distributed in the body let me write here distributive distributive shock now in distributive shock what really happens in distributive shock what really happens we have already discussed that blood volume is 5 liter but in distributive shock capacity is dangerously increased right and if vascular system dilate too much you know normally capacity is how much normally five liters and volume is how much five liters but if capacity becomes 15 liter if capacity becomes too much blood will be pulled in the periphery will the blood is properly returned to the heart to be pumped no and that will lead to failure of heart function but we don't call it cardiogenic shock because primary problem is not with the heart primary problem is not with the heart we cannot blame the pump if we don't supply the pump with the fluid now we have to blame the capacity of the peripheral circulatory system this particular cases we have already discussed septic shock okay let me explain under what circumstances you may have now here is your visa motor center right then these are the pathways which are coming down and from here sympathetic neurons are going really ganglionic sympathetic right and then there are post king linear sympathetic fibers now anything which lead to massive anything which lead to massive visual dilatation which will lead to what type of shock distributive shock now let's look at what could be the conditions of such type of shock one cause of this is neurogenic shock neurogenic shock when we say this neurogenic shock it means something wrong with the nervous system and you know one of the major function of the autonomic nervous system is specially sympathetic nervous system is to maintain the tone in vasculature in a normal person arterials and variants are semi-constructed now if there's major sympathetic outflow problem if due to any reason if sympathetic nervous system is not working arteries and veins will pathologically dilate and there will be peripheral pulling now what could be the causes of neurogenic shock number one cause of neurogenic shock may be vasomotor center failure or vasomotor center depression if you are taking some drugs which are cns depressant someone has toxicity of those drugs that will lead to visual motor center failure right or there may be supposed medullary infections or medullary tumors and the medulla and they may damage the vasomotor center or someone has spinal cord damage spinal cord is severely damaged do you think there can be good sympathetic outflow no and if sympathetic outflow fail again the lot of vessels dilate and peripheral cooling of the blood occur or you have given so this is second number one was problem in the middle central sympathetic outflow fails second cause is spinal cord outflow is problem we also call it spinal shock spinal shock then third is ganglion blocker if you give very big to a high dose of ganglion blocker to someone patient will go into shock then nerve ending blocker sympatholytic drugs you know sympatholytic drugs toxicity always lead to a very sphere problem it may be central sympathetic it may be ganglion blockers and here is a mechanism the drugs which block the release of norepinephrine or the fifth mechanism may be the drugs which toxicity of the drug which block the alpha-1 receptors for example someone has taken toxic doses of preservation or treason which alpha one blocker that will lead to the trouble right or anyone who has any other wizard related drug toxicity whether dilator drug toxicity for example hydrolyzing someone has taken you can say toxic doses of hydraulic gene or toxic doses of minoxidil or toxic doses of any other visual relator naturally all the possibilities will be dilated and that may lead to failure of distribution system that whole the distribution system will be pathological blood will be pulled in the paraphrase and it is not returning so under all these circumstances and another then other group of problem is i told i have already told you that in the perivascular connective tissue there are lot of mast cells in the perivascular connective tissue there are lot of mast cells which are loaded with which antibody ig e and if allergic substance enters in your body if you have made an ige against a particular substance write your particular drug and your mast cells are pre-loaded if your mast cells are already loaded with ige then what really happens that that allergic substance will come stimulate the ige ige will stimulate the mass cell and muscle will release massive amount of yes residual dilators like histamine and again they will be shocked and this this type of shock is called not neurogenic shock this type of distributive shock is in a phyllactic shock then another cause of distributive shock is septicemias we have already discussed that in case of septic shock this is also called warm shock because uh peripheral vessels are not constricted they are rather pathologically dilated in septic shock what really happens a lot of bacteria are there or there are lot of toxins especially endotoxins which stimulate the endothelial cells stimulate the white blood cells and a lot of cytokines are produced and all this culminates into production of lot of visual dilators and vessels pathologically dilate and some fluid also oozes out from the vascular system to the interstitial area because due to increased permeability of micro circulation in septic shock plus because most of the vessels are too mutilated so blood is pathologically distributed in the peripheral part and blood cannot return back to the heart is that clear after that we come to right so we were talking about distributive shock which may be septic shock or anaphylactic shock or neurogenic shock or vasodilator drug shock or one more thing acute failure of adrenal gland if there is acute adrenal insufficiency can you tell me a cause of acute adrenal insufficiency can you tell me a cause of acute adrenal insufficiency okay i'll give you a hint in meningococcal in meningococcemia sometimes both adrenal gland undergo hemorrhagic damage you don't know that pathology is not that good in your mind okay you just trust me i'm right that in meningococcal infections especially septicemia these meningococcy may damage your toxins released from them may damage the adrenal cortex and if adrenal cortex is severely damaged and developed hemorrhagic lens right that will produce severe visualization because vasoconstrictor substances are not produced from there and we see there is acute adrenal insufficiency which lead to the shock after that we go to the next category of shock the fourth category we were discussing was we have already discussed hyperbolic shock and its causes then we have discussed cardiogenic shock and its causes after that right now we discussed distributive shock and errors different causes and now we are left with one and that is which type of shock obstructive shock now we are left with obstructive shock in case of obstructive shock what was wrong with the patient that there was some major part to some part of card there was a major obstruction right to the either luminal obstruction or external compression right and that lead to obstructive shock let me give you some examples of structure shock now what really happens in obstructive shock okay you will understand one example is cardiac tamponade very what is cardiac temponade have you heard of this word cardiac temponade what is cardiac tympanide yes this is your heart and this is around it what is this pericardium right now if there's too much too much fluid accumulated in pericardium normally pericardium has clear fluid and small amount less than 30 ml far less than 30 ml even but if you have too much fluid right accumulated in pericardium then heart is into trouble you know what really happens to heart heart becomes something like this and this is the pathological fluid which is accumulating now you see this pathological fluid which is accumulated in peri cardium it is compressing the both ventricles if it is compressing the both ventricle can they fill properly can blood venous blood can the venous blood easily come into right atrium and leave out no even the can properly left ventricle can fill and eject out no so what we say that in case of pericardial effusions if pericardial effusion becomes so much if pericardial effusion becomes so much that you start compressing the compromising the ventricular filling right then patient will have rising jvp because right heart is not accepting the venous return so patient will have rising jvp number two patient will have fallen systemic blood pressure no when right heart is compressed jugular venous pressure will go up when left heart is compressed then systemic blood pressure cannot be maintained so such patients which have massive pericardial effusion fusion if they start developing rising jvp rising jugular venous pressure falling yes blood pressure and distant heart sound distant heart sound the condition is called cardiac temponade temponates so every pericardium refusing is not cardiac tamponade every pericardial effusion is not cardiac typonate cardiac tymponate is said to be present when cardi pericardial effusion is so much that it is compromising the ventricular filling or obstructing the ventricular flow right and leading to progressively rising jvp falling blood pressure and distant heart sound because when you will try to hear it you cannot hear well because there's a lot of pericardium so cardiac temponade is a condition in which cardiovascular system is compressed or heart is compressed so much that its flow is obstructed is there clear and when flow is obstructive then we say there is obstructive shock so one of the example of obstructive shock is cardiac temponade tempo net right one of the cause of obstructive shock is cardiac temponate then another causes tension pneumothorax tension pneumo thorax what is this tension pneumothorax will tell me what really happens in a patient with tension pneumothorax are you going to explain it to me yes yes here where in the pleural cavity let's suppose someone uh start for example someone get an stab injury here knife step here and a flap like entry of the air forms from the atmosphere to the pleural cavity with every inspiration if patient is taking the air in but during expiration he is not throwing the air out then what will really happen that in this person that air is progressively entering air is filling up the pleural cavity and why we call it tension new pneumothorax mean air in the laurel cavity and why you call it tension because air is under tension that during inspiration it enters but during expression it cannot come out and because it is progressively accumulating so lungs will be lungs will be collapsed and even lung may be pushed to the opposite side and here is your cable system now listen carefully that if air keep on accumulating here right look here if lungs are const progressively being pushed to the opposite side that will produce the major kinking did you know bend or kinking in the major venous flow can blood flow properly to the heart no and that will lead to obstructive shock so in tension pneumothorax again let me repeat it what really happens in tension pneumothorax there is some lyon which is acting like a valve and during inspiration air enters into pleural cavity but during expiration air cannot get out so air is progressively accumulated in plural cavity when air is accumulated progressively under tension it keep on pressing the lungs and lungs when they are being pushed from the air in the pleural cavity towards the mediastinum right mediastinum is displaced and major you know venus input system to the heart that is piranha kevin fiorena they are bent or king to kinked too much and you can say cardiovascular flow cannot be maintained from the venous side to the right heart and that will lead to what type of problem obstructive shock so there can be tension pneumothorax there can be pericardial disease like temponade then of course we should not forget one classical example of obstructive shock that is massive pulmonary this has to be massive there is massive pulmonary embolism embolism the classical example of this when there is massive pulmonary embolism is suppose this is the right heart and this is the pulmonary artery outflow now listen if a big from the leg let's suppose from the leg a big thrombus is moving from here and if it gets stuck over here you know from deep venous thrombosis dvt right from the deep veins of the leg a big thrombus moves and passes through the heart and then it is stuck with the major pulmonary tree now heart cannot it is producing so much obstruction the right heart cannot maintain the cardiac output right and there's major obstruction to the cardiovascular flow system so we call it again that this is one more example of obstructive shock this is one more example of obstructive shock then okay one more cause of obstructive shock you will tell me something what is this there's a tumor here this tumor usually forms in the left atrium and in some patients it may block right and if it this tumor which is usually originating within the left atrium if it blocks the mitral valve there will be severe obstruction to the cardiovascular flow system can you tell me the name of the tumor you must have heard of it yes who will tell me the name of the tumor and then i will tell you you will say you heard of it you've heard of atrial maxima or never heard atrial mixo racial maxoma right there will be obstruction sometimes not in all patients of atrial maxima but in some patients with atrial myxoma there may be sphere obstruction and that's where obstruction may lead to obstructive problem right then in the same way there may be left atrial mural thrombus if a very big neural thrombus is formed here and this thrombus may block is the right left atrial left atrial mural thrombus neural thrombus is that right left ritual mural thrombus right so after that we have completed now the causes of common causes of shock right before i really finish the causes i would like to introduce a very unusual type of situation in which there is syn copy you know how you define syn copy send copy sy syn copy yeah it is transient loss of consciousness due to generalized hypoxia to the cerebral cortex this is transient loss of yes transient loss of consciousness due to global hypoxia to the yes cerebral cortex now why is incomplete occur sometimes uh some people think it's shock right actually it is usually vasovagal situation that in some patients suddenly right due to fear or due to prolonged standing or sometimes even during maturation or during sphere bout of cough right or right they develop severe you can say activity of parasympathetic nervous system and the severe vehicle activity and if that vehicle activity leads to inhibition of heart for few seconds and dilatation a lot of vessels so both things are combined there's low cardiac output with vasodilatory system and they become naturally the cardiovascular system cannot maintain the blood flow to the cerebral cortex and they become transiently unconscious is that right okay let's have a break and then we will go to the stages of shock now we will talk about the different stages of shock stages of shock now when we talk about the stages of shock this is let's suppose that you have a patient some patients with a shock die very soon but most of the patient if they are not treated well then they keep on deteriorating progressively but what really happens that in the first stage biological system is you see biological injury is going on and within the body there are there are mechanisms which will compensate and support it the mechanisms which will prevent the deterioration and supports it but if these mechanisms at this stage where different biological mechanisms right they are activated in our body compensatory mechanisms and they are trying to support the cardiovascular system right this stage is called non-progressive non compensated stage company seated non-progressive stage some people also call it a non-progressive compensated stage of shock what really happens in this stage is again listen carefully that for example this person got an injury to explain these stages of shock we are taking an example that there is a roadside accident you reach there you pick up a patient and you put the patient in your car and now you are taking the patient to hospital on the way patient is bleeding right suppose internally right there's some internal injury also and person is bleeding you are unable to stop the bleeding now initially when bleeding is uh he's losing the volume and shock has started there are some biological mechanism which i will discuss into detail they will try to try to help the cardiovascular system to stabilize and patient is even though passing through a stage of shock but he is not deteriorating rapidly so we say shock is there but it is not progressing to deterioration so we call it non-progressive shock not progressing not progressing to deterioration then if for example on the way if you have not reached to hospital in time right then compensation mechanisms start failing and when compensated mechanisms start failing now you see what is happening it is next phase of shock what is happening here patient is progressing towards more deteriorated state and this stage is called this stage is called progressive stage of shock that is called progressive stage of shock progressive progressive stage of shock during this if you reach hospital and provide him appropriate care right appropriate care proper fluids right and in this case patient can be reversed right and patient will come out of shock cardiovascular system will become stable but somewhere i will explain later why somewhere here patient may go now very rapidly patient is deteriorating right and in this case we call it that this is refractory shock this is called directory shock or this is called irreversible chalk this is called refractory shock or irreversible shock refractory because it is reflected to treatment refractory shock or but more commonly it is called irreversible stage of shock irreversible stage now again listen if a person who is bleeding with moderate speed internally right and his biological system has to fight against the deterioration but of course biological system cannot fight forever again i'm repeating the information this roadside accident you took up one patient in your car you're taking the patient to hospital when you are on the way right initially his biological system compensating mechanisms will be activated in his body to stabilize the cardiovascular system and after that if you still not provided the proper treatment then it will start progressingly deteriorating the patient but still during this phase if you go to the hospital get the proper treatment patient will recover but if you still patient does not get the treatment eventually he will enter into a stage of shock in which situation becomes refractory resistant to treatment or even irreversible and then even you bring the best treatment in the world you cannot save the patient now we will discuss one by one different stages of shock first of all we will discuss into detail non-progressive compensated stage right now we are going to talk about non-progressive compensated stage now when we talk about non-progressive compensated stage let's suppose this is a circulatory system of the patient this is a circulating system of the patient here is the patient or injured patient's central nervous system now what really happens number one bleeding is going on here patient is losing the blood right that is the problem i'm right blood is being lost now how the compensation mechanisms will be activated that is what we have to understand right number one you know that in the cardiovascular system there are carotid bodies carotid bodies and aortic bodies which have chemoreceptors plus there are the rotate sinus which has barrel receptor first as soon as blood pressure will fall as if as soon as blood volume is lost what will happen venous return will be decreased when venous return to the heart is decreased naturally cardiac output is decreased and cardiac output is decreased then spirited sinus is less stretched right you know the rotate sinus has barrel receptors which keep on measuring the blood pressure so again bleeding has started venus return to heart is decreased cardiac filling is less cardiac output is less blood pressure is dropping now the slight drop in the blood pressure is sensed by nerve endings in carotid sinus now these nerve endings from the carotid sinus let's suppose these are the nerve endings from the rotate sinus right they will report this information to the central nervous system to medulla their blood pressure is falling right actually listen carefully what really happens that when your blood pressure is high barrel receptor nerve endings are more stretched right when your blood pressure is high their receptor nerve endings are more stretched and they produce more action potential and if they produce more action potential in high blood pressure they keep the vasomotor center suppressed but during the shock reverse happen what happens during the shock blood pressure is falling fall in blood pressure fall in blood pressure reduced stretch of bearer receptor nerve endings nerve endings then reduced action potentials reduced suppression of there is reduced suppression of vaso motor center there is reduced suppression of vasomotor center so with the motor center will fire and with the motor center will fire now you know that sympathetic outflow will occur through a thoracolumbar area the sympathetic neurons right some of the sympathetic neurons they are going to hurt right some of these sympathetic neurons of course through the sympathetic ganglion they are going to vanes some of these sympathetic neurons they are going to supply the smooth muscles on arterial side right some of these sympathetic fibers they will be going to the kidney and juxtaglomerular they will stimulate juxtaglomerular juxtaglomer operators in kidney some of these will stimulate adrenal medulla now what really happens that from these nerve endings the release of norepinephrine and cardiac tissue norepinephrine we know venus smooth muscles norepinephrine on arterial smooth muscle and when juxtapretus is activated this will release renin right in the same way you know sympathetic nervous system also stimulates extra glomerular operators because extra glomerular operators has beta-1 adrenergic receptors plus it will stimulate the adrenal medulla and from the adrenal medulla there is release of what is the release of epinephrine this release of epinephrine so it means that what really happens to this patient that his sympathetic nervous system is activated right again let me repeat what is happening to this person his sympathetic nervous system is one of the early compensating mechanisms which are activated why a sympathetic nervous system is activated there are multiple factors number one baron receptor report that blood pressure is falling so sympathetic nervous system is activated number two horror of the accident produces anxiety and fear that activates the sympathetic nervous system right then if patients see the sphere pain pain will also activate the sympathetic nervous system now let me repeat it again that in a patient who has suffered with injury from higher psychic center right fear and anxiety right these factors will stimulate the from the limbic system emotional centers where they will activate the sympathetic outflow with the motor outflow secondly barrel receptors are reporting blood pressure is falling barrel visor motor system is no more inhibited or released from inhibition number three if patient has broken leg or the sphere pain then ascending pathways of the pain on the way they'll stimulate the reticular formation and also activate the with the motor center so what really happens that psychic psychic fear pain barrel receptor activity all of this is stimulating sympathetic nervous system now it is first biological system which is trying to compensate right to trying to stabilize the cardiovascular system how number one what is happening to the heart the sympathetic nervous system when it is firing on the heart of course and not only neurons are releasing norepinephrine rather from the blood epinephrine is also coming to the heart under the influence of sympathetic nervous system what will happen heart rate will yes now right here the sympathetic nervous system is leading to increased heart rate increased stroke volume even though it increases heart rate which is called positive chronotropic action it increases conduction through ev node you call it positive dromotropic action it increases the automaticity pathological automaticity in the heart which is not good for the patient that is positive bathroom tropic action and of course it increases the contractility of the heart that is positive ionotropic action so all of these sympathetic activity increase the heart rate increase the stroke volume and both of these things increase the cardiac output both of these things try to increase the cardiac output this is number one thing number two thing that sympathetic nervous system will lead to we know constriction sympathetic nervous system is leading to yes we know constriction and when there is veno constriction when you know look here when veins will constrict you know lot of blood is normally pulled in veins about 70 percent of the blood in the body is on the venous side so when sympathetic number system will stimulate the veins we know motor tone will increase when veins will constrict they will squeeze the blood too hard when they will squeeze the blood to the heart cardiac filling will increase preload will increase and diastolic volume will increase frank startling law will be operative again you know veins will constrict push more blood towards the heart right cardiac filling is increased and frank starling law says more you put in the heart more stroke volume is there so we increase venous return will increase interstellar volume and that will be again associated with increasing cardiac output so now you can come to vino construction which is leading to increase pre load and when heart has increased preload that will lead to increased cardiac output right and it means the cardiac output is increased by direct stimulation of hardware sympathetic nervous system and cardiac output is increased by we know motor stimulation and of course you know blood pressure systolic blood pressure depends on cardiac output and diastolic blood pressure depend on systolic blood pressure depend on cardiac output diastolic blood pressure mainly depends on total peripheral resistance so what really happened up to now that cardio stimulation and venous stimulation has increased cardiac output it means these two systems have led to stabilization of systolic blood pressure what has happened these two mechanisms have stabilized the systolic blood pressure is that right now next what is happening there is rtriolo constriction sympathetic nervous system and epinephrine and norepinephrine will produce arteriolo constriction when arterioles are constructed total peripheral resistance is increased again arteriolar constriction arteriolo constriction will lead to yes increase total peripheral resistance increase total peripheral resistance will lead to increased diastolic blood pressure diastolic blood pressure so in short we can say sympathetic overflow by stimulating the vino constriction and increasing cardiac output and directly acting on the heart and creating cardiac output stabilizes the systolic blood pressure and sympathetic nervous system by producing arterial constriction by increasing the total peripheral resistance stimulates uh stabilizes the diastolic blood pressure right so it means normally when you you are going through bleeding process your blood pressure tend to fall blood pressure has a tendency to fall but these compensatory mechanisms are trying to stabilize the systolic and diastolic blood pressure now this is not the only sympathetic activity there are more activities also more compensating mechanisms and what are those mechanisms the other mechanism is one which is sympathetic overflow sympathetic adrenergic system number two number two there is activation of renin angiotensin aldosterone excess now how it is really stimulated let's this is your renal system and naturally blood flow to kidneys decrease is reduced for a few years one more thing which i should have explained and now i'm going to explain sympathetic nervous system is doing one very wonderful thing which i have not mentioned can you tell me sympathetic nervous system in a patient who is undergoing shock does one extremely wonderful thing for the patient which i have not mentioned so can you tell me okay let me tell you the next thing which sympathetic nervous system does is that sympathetic nervous system redistribute the blood from different vascular beds for example that blood flow blood vessels to git blood vessels to git will constrict right blood vessels to kidney will concentrate blood vessels to even more skin to skin will constrict so what really happens in these patients there is these blood vessels will constrict scrutinous blood vessels so planktonic blood vessels will also construct even renal blood vessels will also construct so actually most of the blood vessels will constrict under these circumstances what these blood vessels are doing these vascular beds will constrict so that blood flow to git or to the skin or to liver or other tissues which are not helping in this emergency blood flow to those tissues should be reduced so that the blood which is pushed to the central circulation that should be redistributed to more vital organs that is heart and the brain because sympathetic nervous system does not lead to any significant constriction of cerebral circulation or coronary circulation i've told you previously that cerebral vasculature and coronary vasculature is not under the mercy of sympathetic fluctuations so most of the vascular beds in the body will constrict and the blood will be redistributed in the body and this blood which is saved from other organs is preferentially supplied to the central nervous system and to the heart is that clear now next point which is important is that renin angiotensin aldosterone excess is stimulated now why this axis is stimulated why there is more renin release why there is more renin relays there are two reasons here number one because there is bleeding going on and sympathetic nervous system is activated renal vessels are constructed so blood flow to kidney is reduced in patient with the shock blood flow to kidneys reduce number one due to decreasing blood pressure number two due to compensating mechanisms which are activated they produce intense vasoconstriction of renal vasculature when there is intense with the constriction of renal vasculature that leads to what problem release of renin right so reduce renal perfusion will activate the release of renin and you know renin once it is released from the liver the substance is coming coming which is called in geotensino gen so renin will act on angiotensinogen and when angiotensinogen will pass from pulmonary circulation angiotensinogen first of all listen again renin will come out right under sympathetic stimulation as well as due to hypoperfusion and this renin will convert angiotensinogen into angiotensin one right so what is the main function of the renin it will convert angiotensinogen into introduction one angiotensin one will pass through pulmonary circulation and endothelial cells of pulmonary vasculature have enzyme which is called into tension converting enzyme which will convert angiotensin one into angiotensin to angiotensin two now angiotensin two will do multiple functions what are the functions number one inducing two has receptors in the central nervous system near the hypothalamus there is an area called subfornical area sub fornical area and central nervous system when this area is stimulated by angiotensin ii and this area is stimulated by angiotensin 2 patients will feel thirst so thirst is a compensatory mechanism so that patient should drink water that is why if patient is conscious and of course at this stage if patient is really conscious he will ask for water patient will feel more thirsty number two angiotensin 2 will act on smooth muscles smooth muscles of veins as well as arterial arterioles naturally there will be no construction and yes arterial low constriction you know we know constriction increases venous return to the heart and venous return to the heart will need to increase yes increase and diastolic volume that will increase cardiac output and that will lead to increase again stabilization of systolic blood pressure so it means this is another spot for the systolic blood pressure secondly arterial constriction right that will lead to what increased arterial constriction will need to increase total peripheral resistance and increased total peripheral resistance will increase diastolic blood pressure so what really happens that here angiotensin ii by producing the vino construction and increasing the cardiac output right stabilizes the systolic blood pressure and angiotensin two by arteriolo constriction increasing the total particular resistance stabilizes the diastolic blood pressure so again there is another support to stabilize the patient systolic and diastolic blood pressure plus angiotensin 2 is doing one more function and what is that function angiotensin 2 will act on adrenal cortex you know adrenal cortex has zona glomerulosa it has this is zona glomerulosa which has a receptors for angiotensin ii and under the influence of zona glomerulosa right under the influence of angiotensin 2 zona glomerulosa will be releasing aldosterone it will be releasing aldo sterone right so what is happening that angiotensin ii when it act on adrenal cortex zona glomerulosa zonoglobulosa releases aldosterone and this aldosterone is doing which function it will lead to salt and water retention it will act on the nephron principle cells of the nephron and principle cells of the nephron start retaining what salt and water this salt and water what it is doing the salt and water which is retained salt plus water the increase yes the increase blood volume but remember one thing to activate the aldosterone mediated salt and water retention it takes more than half hour it takes some time right anyway the blood volume will increase then what will happen venus return will increase increased venous return will again lead to increase cardiac output and again support for systolic blood pressure now you see there's so many compensatory mechanisms operating in the patient patient is refusing to die biological system is trying to trying to live trying to stabilize its blood pressure right the methodic nervous system has been activated and number one number two rain in angiotensin aldosterone excess has been activated what three major things sympathetic nervous system did was direct action on the heart and increase cardiac output and we know construction increased cardiac output and when cardiac output is increased sympathetic nervous system stabilizes systolic blood pressure then i said sympathetic nervous system do arteriolar constriction and that arterial construction increase total peripheral resistance and that again leads to what type of thing increased diastolic blood pressure then draining angiotensin aldosterone excess how the system is stimulated number one sympathetic overflow beta 1 receptor on the vitamin receptors on the juxtapatters and release of number two when hyperprofusion of the kidney again release the renin and what is happening that this random convert angiotensin no gene into angiotensin one and which in the lungs get converted into angiotensin two angiotensin two can produce thirst angiotensin two can uh produce their receptor on the smooth muscle the veins as well as arterioles we know constriction right that will lead to increased venous return increase and diastolic volume increased cardiac output again systolic blood pressure stabilization number two articular smooth muscle stimulated arterial constriction increase total peripheral resistance again support to the diastolic blood pressure moreover angiotensin to stimulate the release of aldosterone from zona glomerulosa aldosterone lead to salt and water retention this retained salt and water lead to increased blood volume increased venous return increased cardiac output again stabilizing the what systolic blood pressure right meanwhile from posterior pituitary there will be release of adh the other name for adhs vasopressin so there's the release of adh now this release of adh from the posterior pressure tray right that is serving two purpose number one vasopressin will do arterial constriction when vasopressin or adh and high concentration can stimulate arteriolo constriction total peripheral resistance is increased and which blood pressure is increased diastolic systolic blood pressure is on the cardiac output dependent diastolic blood pressure is on total peripheral distance mainly so adh will do two functions number one articular construction which is good for this patient number two you must be knowing adh work on the last part of nephron and retain water and that water which is retained under the fence of adh right that water also increases blood volume increased venous return increase cardiac output again stabilizing systolic blood pressure so look at the beauty of this that person is bleeding loss of blood is trying to destabilize the systolic and diastolic so look here it is really like this that bleeding is trying to take the things down but these are sympathetic nervous system trying to stabilize it this is the range in angiotensin aldosterone excess trying to stabilize it this is the adhd release which is trying to stabilize it right then not only these sense there is also central ischemic response the central nervous system comes really too schematic that again gives another strong burst of sympathetic outflow right after that one more thing which is important is that something called reverse stress relaxation of circulatory system i will explain what is that this is one of the compensating mechanisms reverse stress relaxation of circulatory system reverse stress relaxation of now first you understand this thing stress relaxation attention place blood vessels are a very strange type of tubes if you increase the volume in the blood vessels right what they happen if you put us increase the blood volume there's more stress on the wall of the vascular system and vascular system relaxes and if you decrease the volume then vascular system shrink it means blood vessels have some myogenic mechanism what is that mechanism myogenic not neurogenic that the smooth muscle tube is such a way that if if you put more blood into some vessel right lumen if there's excessive blood more you stretch more it contracts less less to stretch less it contracts what does it mean that when you put the stress by putting extra volume blood vessels will relax but when blood is being lost the mechanism will be reversed so reversal of the stress relaxation what does it mean that volume is lost for example there was normally five liter volume and there are five liter capacity if one liter is lost then cardiovascular system will reduce its capacity so cardiovascular system has a strange quality that the volume increases slightly accommodate increases this capacity the volume decreases to slight extent it can decrease its capacity so by decreasing the capacity of vascular system right by reverse stress relaxation by decreasing the capacity of muscle system you can say vascular system walls are enveloping around the remaining blood is that right again the advantage of that is to prevent the peripheral pulling to prevent the peripheral pulling so that blood keep on returning to the heart and cardiac output should be maintained well and blood pressure should not fall another attempt by the cardiovascular system to stabilize the blood pressure is it clear or should i repeat it is it clear to you or not not clear it's okay good otherwise you can revise the okay next thing so this is also compensating the loss the blood was being compensated being lost after the body and this is a compensatory mechanism now how many things are fighting in the patient these are the fighting to prevent the sympathetic nervous system radiant angiotensin aldosterone access adh system reverse stress relaxation then one more thing occurs which is very interesting look normally what happens first understand the normal you see if we understand any capillary bed suppose this is a capillary bed in any tissue this is a tissue and this is a capillary bed here is arterial input and here is venous output normally what happened that blood fluid is slightly moving from arterial side of capillary to provide the cells with to provide the cells with oxygen and nutrients and the venous capable is fluid is going back is that right so this is what normally happens there when normal hemodynamics are there that fluid from the arterial side of capillary is coming out adding to the interstitial fluid and this fluid is giving the oxygen and other nutrients to the cells taking the waste products and this fluid is going back is that right now when person is going under shock listen carefully now fluid here is more or less there is less so filter filtration pressure filter out pressure is less and suction pressure is more so most of the capillary beds lose less fluid to intestination and get extra fluid from the interstitium right because under the shock situation from the in the micro circulation pressures have dropped because in the micro circulation hydrostatic pressures have dropped so uh starlings forces which are concerned with the micro circulation they are altered so rather than that equal output and you know equal amount of fluid leaving the micro circulation and entering to micro circulation this is a different situation less fluid is leaving the micro circulation and more fluid is taken up by micro circulation and other attempt by the body to stabilize the blood pressure right of course this is the interstitial fluid which is being shifted to where vascular compartment is that right so micro circulations are sucking the fluid from interstitial area and taking up to the vascular compartment in the same way git water absorption is also increased so you can say the shift fluid shift fluid shift is occurring to this patient fluid shift from interstitial fluid moving towards the vascular fluid am i clear interstitial fluid is shifting to the vascular fluid right so these are some of the compensatory mechanisms which are fighting for the patient and trying to stabilize this blood pressure let's suppose uh you are about 40 kilometers away from the hospital you have taken the patient from there and you have just come for 20 kilometers and during these 20 kilometers person was bleeding so this bleeding was trying to take it down but these compensatory mechanisms were trying to stabilize it so patient does have shock but this shock is not progressing to deterioration this shock is well compensated by the biological compensatory mechanism am i clear to this stage now let's suppose that you are midway to hospital now halfway and there there's a traffic jam now you are in a trouble there's a traffic jam you cannot rush you are doing peeping but people are not understanding that you are having a patient who is shocked and they should give you away and of course you don't have anything like ambulance router or other things right now what happens for significant time compensatory mechanism have operated in such a way that most there was arterial constriction to most of the tissues so most of the tissues were sacrificing their blood flow for the sake of blood flow to heart and to the brain is that right now around this time around this time problem will start right but before i discuss this time this stage i would like up to now what were the clinical features up to now patient was having rapid pulse thready pulse patient was having cold extremities due to vasoconstriction patient was having ashamed gray color is that right up to now patient was looking very very anxious of course you can understand why sympathetic overflow anxiety fear is that right this was all during the compensatory stage in compensated state most of the organs were sacrificing they had intensely reduced blood flow and this sacrifice was to provide more and more blood for heart and brain so that vital organs should remain alive is that right and meanwhile maybe even kidney is at the verge of necrosis but still it is reducing its blood flow because kidney can make urine later on it's a time to keep your heart and brain working now you are in the traffic jam your car is stuck biological compensating mechanisms are not having unlimited energy they also start getting exhausted now bad things will start happening i will tell you what bad things will happen some very bad things will start happening around this time now patient will start deteriorating now components actually what is the bad thing the bad thing is at this moment you're halfway you are in the traffic jam and compensating mechanisms are now failing they are exhausted they are failing now tissues are protesting that we have given enough sacrifice to maintain the blood flow to for cns and to the heart so compensation mechanisms now not working well and now deterioration will start but even if during this stage if you give a good treatment you can save the patient but the problem is that you are stuck in the traffic jam now while you are in the traffic jam we see what happens in the patient body right now i told you that patient compensating mechanisms have done enough sacrifices many tissue has sacrificed and now compensating mechanisms will be blunted and patient will go into progressive stage what really happens in progressive stage let's look at the situation number one thing for a very long time there have been sphere reduction in blood supply to the peripheral tissue i told you most of the peripheral tissue like git liver skin and many other tissues they were they were having vasoconstriction so it means for a very long time this peripheral tissue was having reduced blood flow right naturally they were reduced oxygen supply when they were prolonged reduced oxygen supply to the peripheral tissue naturally the metabolism will alter that these cells in the normally in the presence of oxygen they are capable of breaking the glucose up to pyruvic acid and then if oxygen is available pyruvic acid will go into citric acid cycle and convert into lot of atp now what really happens in this patient as oxygen is not available enough so pyruvic acid will go into yes lactic acid and this lactic acid will come to the circulation and tissue has been most of the vessels in the body during the compensatory stage when they have been constricted then many tissue have been skimming for very long time and because they have been ischemia for very long time for many many tissues these tissues switch their metabolism from aerobic to anaerobic situation and during anaerobic glycolysis there's massive release of lactic acid so what is happening that there is release of lactic acid from those tissues now when release of lactic acid is there lactic acid after the vasodilator lactic acid act as a vasodilator is that right plus lactic acid act as a myocardial depressor plus lactic acid act as a myocardial depressor now when it it is trying to visibility now look at the sympathetic nervous system and angiotensin ii and other compensating mechanisms compensating mechanism for trying to with a construct but now these tissues are very angry they have been giving sacrifice and yet patient is not in hospital and getting good treatment so these tissues start start producing lactic acid lactic acid start producing vasodilation now there will be a fight between vasoconstrictor mechanisms which are compensatory and between the opposite mechanism like vasodilatory mechanism and these visual electrical mechanisms like lactic acid or carbonic acid or carbon dioxide which is being produced by the tissue and not removed from there right so gradually the response of peripheral vasculature to sympathetic constricting effort will reduce so we see at this stage at this stage now tissue will become peripheral vessels will become resistant to the visor pressure action of the compensatory mechanisms and they will start dilating now when they will start dilating it means the blood which was already less in the circulatory system because patient was bleeding so what will happen there will be pooling of the blood blood will pool in the peripheral area when blood will start pulling as vessels are dilating venous return will be less and venous return is less cardiac filling is less cardiac output is less at the top this lactic acid will directly also depress the myocardium right cardiac output will drop due to two reasons number one peripheral visibility peripheral pooling of the blood which has started just now it has reduced the venous return and cardiac output has become less number two that there is myocardial depression started and that is another contributing factor that cardiac output will be less when cardiac output will be less now listen carefully and cardiac output will be less then another trouble will start further hypoxia to the tissue further lactic acid further pooling more reduction in venous return more fallen blood pressure further drop in cardiac output and further lactic acid so a positive vicious cycle will start do you think it's good for patient or bad yeah it's very bad for the patient already he's losing the blood and now blood vessels start dilating then there's another trouble that sometimes is hypoxia is so severe and prolonged that even endothelial cells are hypoxic and injured and when endothelial cells are injured these endothelial cells start producing nitric oxide and this nitric oxide also contribute into further vasodilation plus this nitric oxide also act as myocardial depressant if you think good things are happening to patient or bad now the very bad things happening to the patient right that in the patient's blood lactic acid level is increasing carbonic acid level is increasing nitric oxide levels are increasing all these things the cardio depressant at the same time peripheral vessels are dilating so now cardiovascular system which was previously stabilized by the compensatory mechanism now it is truly destabilized now patient's blood pressure will start falling significantly is that right meanwhile when this mechanism is occurring blood flow which was previously well maintained to central nervous system will it be maintained now for the central nervous system no the central nervous system will not be maintained uh with proper profusion and lot of acid is going to the central nervous system what is happening or carbon dioxide right even visual motor system is itself suppressed where's the motor system is itself suppressed it means sympathetic outflow will reduce it means constructor mechanisms will fail and time is coming when compensating mechanisms are shutting down going down and there's a dietary mechanism and myocardial depressive mechanisms are overwhelmingly active is that right not only this another trouble will start meanwhile and that trouble is that from the git that git when it remain ischemic for long time and git remain is giving for a long time because in early stage of shock they have been very intense ways of construction some planktonic vasoconstriction to jit so what will happen from git swear prolonged ischemia to git may produce necrotic patches and mucous of git when multiple small necrotic areas form git mucosa then bacteria from the git from the broken mucosa will come to the blood and endotoxins and bacteremia and septicemia these problems will start another bad thing happening another bad thing happening right so this patient has severe myocardial depression this patient has visible motor center failure this patient has another treasury look here when endothelial cells were injured i told you number one they will produce nitric oxide which will produce vasodilation number two nitric oxide will produce myocardial suppression presumably another thing when endothelial cells are injured by hypoxia they become more sticky to blood contents right they activate the coagulation mechanisms this is the risk of dic disseminated intravascular coagulation number two that platelet starts taking their micro circulation become fast or slow it becomes slow and sludging in micro circulation occur so it's not acting as a good microcirculation which brings the new nutrients and removes the waste product is that right so what we have learned that lactic acid is more carbonic acid is more arteriolar dietary mechanisms are there visual motor center has flopped myocardial depression is going on git is also releasing different type of toxins to the circulation is that right and last thing that injured endothelium in multiple tissues becomes so much shrunken that fluids start leaking from the inter endothelial gaps so again this is good or bad it's bad is that right so how many bad things happen lactic acid was there carbonic acid was there nitric oxide was there endotoxins were there from git lot of bacteria are there and all these things feel the response of peripheral circulation to the vasoconstrictor mechanisms right cardiodepression is there and progressive cardiodepression and progressive dilatation of peripheral circulation will lead to more and more failure of circulatory system is that right now as patient now his blood pressure is falling even meanwhile uh the acute tubular necrosis may have occurred to the kidney because in the kidney nephrons proximal convoluted tubules need lot of oxygen and when they are they remain ischemic for a long time even renal shut down start right even if still you reach to hospital you can save your patient you should give him blood if you stop the bleeding you replace the volume right you can save your patient right right now you came out of the traffic jam and hospital is now about 15 kilometer away you rush there but patient is somewhere here right now patient is coming down from this stage he is entering into refractory and irreversible stage and you are not yet in hospital what is happening at the stage now i will talk about the next stage and what will happen at that stage we will come to the last stage you are very near to the hospital right but patient is entering into refractive stage or irreversible stage what happens at irreversible stage that all the tissues and cells start committing suicide right life is probably not worth living now for example for a long time up to now by the time patient is at this stage there is severe deficiency of atp if there's sphere deficiency of atp do you think sodium potassium 80 pages which are present on every cell will they be working no when sodium potassium atpases are not working these are sodium potassium atpases when they don't work what will happen sodium will start accumulating in and potassium will start leaking out is it good it is not good right that extra cellular k times will start leaking in like sodium and calcium are more outside the cells so they will start coming in and potassium is more inside the cells it will start leaking out so it means cell membranes in the absence of prolonged absence of atp cannot act as selective barriers and they cannot maintain the calcium and sodium more outside the cells and they cannot maintain more potassium inside the cell so sodium and calcium are coming and this is a sign of injury to the cell and potassium is leaking out this is number one then another trouble which is there is about the lysosomes that let's suppose here's the lysosome prolonged deficiency of atp plus lot of acidosis acidic situation a lot of acid present in blood as well as in the cells because oxygen is not there so electric acid is being formed and even carbon dioxide is not washed away so carbonic acid is also accumulating this will damage deficiency of atp plus excess of protons this will damage the lysosomes so lysosomal enzymes will start leaking within every cell every cell has started committing suicide but remember you are very near to the hospital but in the patient body what's happening from every cell membranes are failing lysosomal membranes are failing and lysosomal enzymes are coming out and these hydrolytic enzymes hydrolases they start damaging the local tissue you can say intracellular structures heavily do you think now the cell is in good shape or bad shape mitochondria meanwhile in most of the tissues my stochastic will fail as power houses and now worst thing is going to happen i told you that atp level is now more or less atp level is less and if atp level is very less rather cell is unable to make atp so it is converting all of its atp into first adp and then into amp and even phosphate is removed from there what is left is adenosine again let me repeat it that atp in the cell has been converted into adp then amp and eventually in adenosine adenosine can very easily come out of cells adenosine and it will go into blood and convert into uric acid and uric acid can never go back to the cells it cannot enter into cell and now you exactly reach to hospital there's a very good intern there patient is of course immediately taken to this and what he will do if he is very wise and if he can do he will stop the bleeding he will stop the bleeding point he will start infusing the colloidal solutions of course best will be if he can get immediately mashed blood if blood is not available he can give albion or he can give gelatin or he can give different type of large molecular weight carbohydrates he start infusing higher molecular weight substances so that osmotic pressure in the blood become high and blood pressure should be maintained even his heroic effort becomes somewhat successful and cardiac function is going on still patient is still alive blood pressure even slightly recovered but even he does the best thing in the world most more chances are patient will not survive you know why because he has gone into advanced stage of irreversible they have been irreversible injury to the cells cell membranes have failed by now all biochemistry is disturbed potassium has gone out of the cells sodium and calcium has come into cell power houses mitochondria have failed lysosomes have released lot of destructive enzymes within the cell and the worst of everything attention plays the worst of everything adenosine has leaked out into uric acid even if you supply the blood flow to the tissues even if you supply the oxygen even if oxygen go inside is there any adb to be converted into atp is there any amp even if there's there's no adenosine so you cannot make amp you cannot make adp you cannot make atp so in this case patient is even though living but they say experienced doctor will say patient has gone to which stage irreversible shock stage he's bound to die recently they started calling the irreversible state with refractive stage because they have saved few patients from this stage so this is very difficult stage to manage because when you give vasoconstrictor substances vessels don't constrict when you give cardio stimulation hard cardiac output and when you make the volume of the lost volume you make it good still cardiac output does not come up they say this stage is refracted to treatment but even at advanced stage of refractory it really becomes truly irreversible and every cell has committed suicide and then you cannot do much so in the last event what really happens that is resistant with the dilation which is not responding to video pressure agents there is severe myocardial depression and every cell is killing itself by releasing mitochondria releasing lysosomal products and by releasing its adenosine and cells become extremely deficient in high energy phosphate reserves is that right i'm sorry you lost your patient but you traveled a lot okay few more things if you do autopsy of this patient what you will find there number one in central nervous system you will find some neurons which are dead in the heart you will find some micro infarct type situation due to prolonged ischemia in the liver you will find that some cells very vanilla cells they have undergo fatty change or they have been necrotic in the kidneys you will find cells in the proximal convoluted tubular area have been the crotech in the adrenal cortex it's very important finding very commonly the austrian usmle about it that adrenal cortex cells which are usually rich in fat globules they will be depleted of fat globules because those cell as a last effort they were trying to convert that fat to con and make more aldosterone or from that fat globules they were trying to make acid cortisol right and other products to fight the stress is that right then in this patient if you study git you will find micro in fart and the git and in some of these patients but more commonly in septic shock patients you find that in the lungs in the lungs lungs micro circulation has been heavily heavily damaged and lungs have become edematous especially in septic shock and we see that this ards adult respiratory distress syndrome so how many tissues central nervous system will have loss of neurons heart will have loss of myocardial cells a liver will have a parasite necrosis a very prominently proximal convoluted tubular cell in the kidney have been necrotic is that right and uh for git illustration that they are you can say from git mucosal necrotic areas are there and adrenal cortex uh adrenal cortical cells fat globules have been deflated in a very special function in the last moment of his life to convert the fat into aldosterone and to convert that fat globules or lipid rich areas into cortisol and attempt to fight with the stress right so now we will be discussing about septic shock septic shock and septic shock is presently the number one cause of death in intensive care units in usa septic shock is presently the number one cause of death in icu patients intensive care units in usa you know how many people die with septic shock every year with the best of the best care only in usa two hundred thousand two hundred thousand people every year die only in usa with the septic shock right and septic shock has mortality somewhere between 25 to 50 percent mortality it's a very high modality and this is all the data from usa not from the third world and the worst of the news is that with all our advances in understanding the organisms and antibiotic and chemotherapy the worst of the news is that septic shock cases are progressively increasing you know why these days septic shock is getting more common day by day because chemotherapy cancer chemotherapy is more commonly used so more people are immunosuppressed because steroids like drug or other immunosuppressive drugs are more commonly used for transplant patient or for the patient with autoimmune diseases right or of course a patient of aids are also increasing in number so what really happens that in this modern era of medical sciences there are more people who are immunocompromised than ever before more people who are living longer more people who are living for long time with diseases there are more people who are taking anti-cancer therapy more people who are taking immunosuppressive for autoimmune diseases a lot of people who are taking immunosuppressive for the transplant reasons so due to all these reasons naturally this big big portion of population which is immunosuppressed right this segment of population is very very vulnerable to more infections and many of these end up with the septic shock right what really happens in before we really go into septic shock i want to know what is the term bacteremia means there is a term called bacteria there's another term called septicemia septacemia you must know what is the difference in bacteremia and certasemia then there is another condition called endotoxemia endotoximiando toxemia right so can you tell me the difference between these terms that first of all you have to tell me what is bacteremia yes what is bacteria [Music] present in the blood and how bacteria is different from septicemia no no look do you think today you got bacteremia did you get today bacteremia did you get daily bacteria answer is yes bacteremia means simply the presence of bacteria in the blood presence of bacteria in the blood venue tooth brush few bacteria do enter in your micro circulation so the git small cracks in the lumen of git are the mucosa of jit with some small bacteria enter into blood right so what really happens that bacterium is one of the common thing you are working in kitchen you get a little cut some bacteria do enter is that right so bacteria is a very common phenomenon that bacteria may jump into your blood but in a person who is these bacteria which regularly keep on entering or coinally keep on entering into your circulation these bacteria caught by your defenses and destroyed so bacteria not very rare is that right it's the some of something common you do shave in the morning and if you cut produce a cut here you get bacteremia is that right septicemia is a very horrible situation bacteremia is something not that dangerous septicemia is a really big problem septicemia means bacteria present in your circulation and they're actively multiplying that bacteria are using your blood as a blood culture right this is a very big difference just bacteria inadvertently enter into your blood and then they are caught and destroyed by your immune system this is called bacteremia but if bacteria enter into your circulation and they just start actively multiplying and damaging the condition is called septacin endotoxemia mean that in your blood lot of endotoxins are present androtoxins are special lipopolysaccharides which are specially present in gram negative bacteria lipopoly saccharide endotoxins are special type of lipopolysaccharide which are present in gram negative bacteria you know the difference in gram negative bacteria and gram positive bacteria gram positive bacteria has inner membrane this is gram positive gram negative bacteria also have inner membrane but the difference is the gram positive have lipid bilayer and outside that it has lot of peptidoglycan layer what is this layer gram positive a very thick layer of peptido glycon right gram negative has gram negative bacteria have very thin layer of peptido glycan and they have additional outer lipid bilayer they have one more lipid layer so gram negative positive have only inner lipid layer and outside they have peptidoglycan gram negative have inner lipid layer and then outer lipid membrane and in between that it has a thin peptidoglycan layer now in gram negative when we say that there are outer lipid layer in this outer lipid layer there are special type of lipid a this is a special type of lipid a and this lipid a has a core carbohydrate it has a core carbohydrate and with that it is having polysaccharide tail again let me show you here there's lipid a this is lipid a right lipid a and with this lipid a there's core sugar and with that it's a long tail of poli saccharide remember in all gram negative in all gram negative organisms lipid a and core protein is same but in different gram negative organisms polysaccharides are different in different gram negative organisms polysaccharides are different so we can say that whole all the structure is called yes endo toxin so endotoxins are mainly present in gram negative bacteria and all the gram negative bacteria have lipid a and core sugar same but from bacteria to bacteria for example salmonella shijayala seresia all of them have androtoxins but their endotoxins have same lipids same core sugar but they are having different polysaccharides is that clear to everyone so you can say polysaccharide is unique to a particular group of gram negative bacteria gram positive bacteria and fungi do not have endotoxins gram positive bacteria and fungi do not have exactly the molecule like gram endotoxins but gram positive have some similar molecules like these are called endotoxin-like molecule androtoxin like molecule but ground gram positive bacteria do not have any true antitoxins is that right it means that what is the difference in endotoxin and exotoxin by the way what is the difference between endotoxin and exotoxin is when a bacterial that produce a touching outside in the blue okay and and the toxin is when a battery [Music] okay let me tell you let me tell you endotoxins are the toxins which are integral component of bacteria write it down endotoxins are the toxins which are the integral component of bacterial structure they are only released they are usually released when bacteria die when bacteria fragment down then endotoxins are released so endotoxins are the toxic substances which are integral component of the outer lipid membrane of gram negative bacteria and they are usually released when bacteria diagram negative bacteria start dying endotoxins are released exotoxins are released by the living bacteria right so endotoxins are the part of bacteria but exotoxins can be released by the bacteria now the point which you remember that exotoxins can be released by gram negative as well as exotoxin can be released by gram positive this is exotoxin exotoxin is the substance bacteria can release when it is living itself right another point which is important let's compare androtoxin and exotoxin number one endotoxins are limited only to gram negative bacteria exotoxins may be in from gram negative or maybe from gram positive number two endotoxins are integral structure of the ground negative bacteria another toxins are not the integral structure they are released by the living bacteria right number three endotoxins all of them work in the same fashion endotoxin come from salmonella or antitoxin come from klebsiella endotoxin come from e coli all the endotoxins damage our body in the same way but exotoxins for different bacteria produce different effects in the body exotoxins from different bacteria produce different effects in the body for example there is exotoxins called coming from the baseless tetanus that produces stretchness but different as a toxin come from the bacillus bottle bottlenum and that produces a disease flaccid paralysis right in the same way that there are some other toxins which which act as enterotoxin and produce diarrhea nausea so what i'm saying that different bacteria produce different types of exotoxins but all the gram-negative bacteria produce same type of antitoxins as far as lipid is concerned because lipid a in all the gram negative bacteria the endotoxin is the same and it is the lipid a which is a more dangerous component which is producing the disease to us so we can say that from three different bacteria if endotoxin enter into three different patients listen we take endotoxins from three different bacterias and inject into three different patients all patients will develop the similar problems with endotoxins but if you take exotoxins from through different type of bacteria injecting different patient they will get different diseases endotoxins act generally exotoxins act specifically for example some exotoxins work only on the nervous system some microtoxins work only in the heart there some extra toxins will damage only the kidney so exotoxins go for a particular target tissue but endotoxins have general effects then another thing very important you already know structure of endotoxin is lipopolysaccharide structure of endotoxin is lipo polysaccharide and structure of exotoxin is usually a protein that is a protein exotoxin is that right it means androtoxins are relatively heat stable but as the toxins are destroyed by the heat because proteins are damaged so we can say endotoxins are heat stable exotoxin the heat labile now we come to the most important difference usually endotoxins do not induce the antibodies if i give you injection of endotoxin you will not make antibodies against endotoxins so our immune system does not protect us against androtoxin if you have a previous attack but against a specific exotoxins usually our immune system make antibodies because exotoxin the proteins and our immune system love to make antibodies against the foreign proteins is that right due to that reason many other toxins can be used as vaccination material if you take an exotoxin and partially alter it partially change the exotoxin in such a way that the other toxin can activate the immune system but cannot produce disease such exotoxin is called toxide what is it called oxide what is toxid exotoxin which is altered in such a way that exotoxin will not produce a disease but still activate the immune system right then it means that if such toxicide is injected into your body you will make antibodies against that substance but if i inject you repeatedly with endotoxin you are not going to build an immune response it has a big significance that if you suffer with one endotoxic attack and you recover you are still vulnerable to another attack in your life but if you get let's suppose uh you suffer with diphtheria and toxin and you survive then you are having immune defense against that am i clear any question here right now it this discussion was just by the way that i wanted to tell you what is endotoxin as a condition when your body has lot of negative organisms and those are gram-negative organisms are dying and when ground negative organisms are dying endotoxins are being released from there from their structure right and [Music] 70 percent of septic shocks are about seventy percent of the septic shock are due to endotoxemia it means that seventy percent of the patient who die with the septic shock they were having gram negative organism is that right because gram negative produce endotoxemia so you know what is bacteremia it is the innocent situation benign situation in which bacteria are just present in your circulation septicemia is a condition in which bacteria are not only present they have beat rather bacteria are beating your defenses and they're multiplying actively into your blood and endotoxemia is a condition where ground negative organism will release a lot of lipopolysaccharides into your circulation am i clear another condition is called piemia i would be impressed if you tell me by emia what is biaemia primia the condition when pus from some area directly enter into circulation we call it piemia what is pimea when passed from some area right enters directly into circulation we call it biamia is that right by any other condition for example you have an abscess here and if obsessed rupture into a small vein and some past center to vein and past globules of moving into blood we say you are suffering with biaemia it's just more dangerous than any of the others yeah it can it can turn up eventually into septicemia when bacteria will start multiplying in the body it's very dangerous there's another condition but that confuses like that empirima have you heard of empima how it is different from others have you heard of it or never on the surgical floors you how empowerment is different from yeah it is infection all of them are infection my friend empima is localized collection of past localized collection of plus plus sorry localized collection of past in an epithelial lined area look here here is your lever and you must be knowing these structures i hope is that right now look here if in the gallbladder lot of pus is collected what is collected lot of bus is collected now this bus which is present in the gallbladder this is called gallbladder empima what is it called gallbladder empima right from sometimes focus of empyema a lot of bacteria enter into your blood and produce septicemia or septic shock okay you must be knowing what is abscess what is the abscess what is the abscess localized collection of pass that is a localized collection of bus right anyway these were just a few terms we were talking about we have already discussed septic shock is a very dangerous situation it is the number one cause of death in ice is used in usa every year more than 200 000 people die simply by a septic shock only in usa right mortality rate in this patient is very high with all the modern management mortality is somewhere between 25 to 50 percent and then i've told you that these patients are day by day increasing because more and more people are immunocompromised these days due to aids and due to chemo cancer chemotherapy or due to immunosuppressive drugs right then i was talking about that and i've already told you that seventy percent of the septic shock are involving endotoxic release now i'll tell you exactly how the endotoxins work are you interested to know how the endotoxins work right how the lipopolysaccharide work because if you know that how the polysaccharides work lipopolysaccharide work then you really know how most of the gram negative bacteria can produce androtoxic shock right so we will talk about now how the endotoxins work look at this bacteria first this is the bacteria this is its inner membrane and this is its outer membrane and this is having peptidoglycan as a sandwich between the inner membrane and the outer membrane so what you call this uh situation is a happy bacteria but if it dies right it will release it what it will be releasing lipopoly saccharides that is lipid a with core sugar with oligosaccharide chain now lipopolysaccharide let's suppose this is a lipopolysaccharide which is released by the bacteria this is a lipopolysaccharide now when these lipopolysaccharide come one of the very important function of lipopolysaccharide is that if they are released into your circulation if these lipopolysaccharides are released into your circulation they will you know bind with special proteins and these proteins are called what are the name of these proteins yes lipopolysaccharide binding binding proteins right you may be thinking why i'm going into this detail there's a very latest trend that they are trying to find the drugs which can neutralize these proteins right or alter this protein anyway lipopoly polysaccharide bind with these proteins and after that they will eventually go and stimulate the endothelial cells they have a capability to stimulate endothelial cell or they can stimulate monocyte macrophage let me tell you if there's one cell here suppose this is a macrophage cell now what these lipopolysaccharide will be doing that this lipopolysaccharide will bind with the special type of receptors on endothelial cell and this special receptor is called a very special receptor right and you know what is the name of this receptor cd14 it's a special type of protein right what really happens that this will be transferred to a particular target cell which may be endothelial cell or which may be a macro phase or monocyte once this reach here now this what is this lipopolysaccharide bind with which molecule cd 40 this will bind with the cd 40. bind with the cd 40 right after once binding with the cd40 what it is doing that there is one more molecule which is called tall like molecule toll like this is called tall like receptors then what really happens after binding here right the cd40 then it will stimulate the tall like receptors right and when it will stimulate the tall like receptor it will give signal to this cell nuclear machinery and within this cell its genes will be activated this genetic material will be activated and it will produce of course messenger rnas and from here it will start releasing lot of dangerous substances and these substances are different type of cytokines these are different types of cytokines right so what did we learn the lipopolysaccharide bind with the its binder protein the reach to the target cell which are usually endothelial cell land what is this funny thing macrophage monocytes there they bind with cd14 again what's the importance of this to learn now they are trying to make some drugs some injections which are just us having soluble 3d protein they are having soluble cd14 if you inject the soluble cd14 look here if you inject the soluble cd410 then this will bind with the soluble 3d protein but soluble 3d proteins are injected from outside so this will become busy with that and it will not have enough concentration to attack our real cell this is one of the pharmacological approach near future may be coming that they are thinking the patient who have endotoxemia they're very high mortality if you inject them with cd14 molecules then lot of androtoxin will bind with cd protein molecule and then they will not go to the uh those 3d proteins which are present on our cells so they cannot activate our cells am i clear then intercepted on the way then look these enter talks so what what really lipopolysaccharide do lipopolysaccharide activate endothelial cells and macrophages is the right monocytes and then these endothelial cells and macrophages they produce lot of what cytokines and these are the cytokines which produce the clinical features which we develop in endo endotoxic shock right these are the cytokines which are elevated in blood in very high concentration and these cytokines basically produce damage to us one more point which is very important that when endotoxins work on the endothelial cells there is endothelial cell activation there is endo cells activation they are activated endothelial cells number one and they will release more nitric oxide and this will lead to strong visa dilation more nitric oxide endothelial cells under the influence of lipopulse endotoxin stimulation will produce lot of nitric oxide so most of the blood vessels will dilate if most of the blood vessels will dilate you know what will happen you will go towards shock if many vessels are pathologically dilated blood will pool into peripheral area you will develop distributive shock is that right plus endothelial cell will shrink and some fluid will be also lost outward so when you have septic shock many many blood vessels are dilated right and those blood vessels which are dilated due to cytokines activity and release of nitric oxide right even these days now there's a modern trend they are trying to build the drug which can neutralize nitric oxide that's the right they are working a lot you know 200 000 people die so they're working a lot to find some way to intercept the function and tragedy induced by the lipopoly saccharide right so what they are thinking that maybe if some drug can be injected and they can neutralize nitric oxide visualization is reduced because in septic shock there's massive vasodilation and blood is distributed in the peripheral part of the body and venous return is reduced cardiac output is reduced of course due to this vasodilation in patient patient of septic shock pulses rapid and bonding not thready weak pulse there's strong pulse and palms are warm but in case of hyperbolic shock due to vasoconstriction body becomes cold hands become cold so face and the hand become cold and clammy in case of hypovolemic shock due to severe visor construction right but in case of septic shock there is severe weather dilatation is that right due to that reason some people call this warm shock what they call it warm chalk number number two many of these patients may have fever also but when i talk about fever you must know every patient with septic shock does not have fever and there is something very surprising that 50 15 15 of the patient with septic shock have hypothermia hypothermia why i'm telling you this thing that don't expect that every person who has septic shock would have high high temperatures the unfortunately there are some people who have even hypothermia i will talk about why because many toxins act on the hypothalamus and disturb their temperature regulation and five percent of patients with septic shock never develop fever they remain normothermic they remain five percent of patients remain normothermic normal temperature fifteen percent of temperature less than normal of course what is left behind eighty percent these eighty percent have fever these eighty percent have fever is that right so these eighty percent have fever now see that this is ground negative organism and when it disintegrates it releases a lot of endotoxins endotoxins bind with lipopolysaccharide binding proteins and eventually they get transferred to the cells which are having 3d protein molecules these cells are monocyte macrophages as well as endothelial cell they bind with cd14 molecules and these lipopolysaccharide activate tall like receptors and this is the surface give signal and under the influence of those signals these cells start producing they start producing cytokines now the different cytokines are produced as a wave first of all this production of interleukin one okay first of all in the blood there is a high level of lipopoly saccharides that is followed by high level of yes place high level of polysaccharide lead to the production of lot of tumor necrotic factor and after some time you'll find there's a high level of interleukin 1 after that you'll find high level of interleukin 6 and 8 then there's a high level of platelet activating factor and nitric oxide so what we really see that in the blood of the patient the digestive which appeared first of all was lipopolysaccharide and lipopolysaccharide when stimulated endothelial cell and especially macrophages the macrophages produce a lot of human necrotic factor in the body tumor necrotic factor activate more macrophages and more endothelial cell and lot of interleukin 1 is released interleukin 1 act on many tissues but low concentration it will act on endothelial cells and endothelial cells will release interleukin 1 8 and 6 and 8 and eventually all the endothelial cell and all the macrophages will start producing very dangerous substances like platelet activating factors so that coagulation system will disturb and they will also produce lot of nitric oxide so there will be massive dilatation in the body so what we really see that lipopolysaccharide lead to release of cascade of cytokines in the blood a lot of cytokines are released in the body now these cytokines when they're present in low concentration low amount they are good for us they help us to kill bacteria but when the cytokines are more then they become dangerous for us now let me tell you how these cytokines are dangerous for us now we'll talk about that what happens when cytokines are in low concentration and eventually what happens when they are in high concentration let's suppose there's a patient here and this is a circulatory system of course now we'll see what are the effects of cytokines in the body here is your patient's pulmonary system and there lies its liver right here is bone marrow house bone marrow house and then of course we should not forget you are something very good and that is called central nervous system having hypothalamus here with interior and which artery now what really happens when bacteria when bacteria are releasing androtoxins and endotoxins are activating the monocytes right as well as these are activating the endothelial cells right in low concentration first i will talk about low concentration what happened that this lead to number one activation of this is neutrophil this is monocyte so activation of activation of neutrophils and monocytes so it means when bacteria come in our body endotoxins they stimulate our white cells and white cells become more active and white cells become more active the addition of bacteria so in small concentration these cytokines are good for us is that right and these lipopolysaccharides lead to the formation of cytokines and cytokines are good for us and of course cytokines activate the endothelial cells and endothelial cell undergo inter endothelial gaps are formed as endothelial cells are activated and that releases antibodies in this area and that releases complements and even in low concentration we can say that cytokines ends in low amount what they are doing the cytokine they are doing following things number one activate white cells neutrogen macros is good or bad number two they activate endothelial cells and endothelial cells produce edema fluid and release the this increased permeability and that leads to you can say release a little bit nitric oxide so locally blood vessels become dilated so that more blood can come into injured area and in the same time they break down c5a and c3a i mean they break down the complement they activate the complement right the cytokines and if complements are fragments c5 and c3 are produced at the site of inflammation and bacteria these complements also help in removal of bacteria is that clear for example c5a can attract more and more neutrophils right and c5a and c3a both can activate mast cells and local inflammation will be produced so up to now it is good so when cytokines in low concentration this is good that they produce local effect and those local effect enhance inflammatory action and enhance the innate you can say immune system and help in elimination of bacteria but when cytokines become moderate concentration when cytokines become moderate concentration now they will start some other things number one cytokines with moderate concentration will move to the liver cytokines with moderate concentration will go to the liver and they will activate the liver cells and liver cells will start producing the proteins which are called acute phase protein acute phase reactants reactants that when these cytokines become more in number right they will go to the liver they will force the level to release certain types of proteins which are called as a group acute phase reactants or acute phase proteins these proteins also help in elimination of bacteria but remember these some of these proteins also contribute in rising esr and some of this protein is called c reactive protein and the protein which is out of this group which is called c reactive protein that is diagnostically used to check that is there an inflammatory condition in the body or not then some of these cytokines will go to the bone marrow and from the bone marrow they will release what neutrophils so patient will develop neutrophilia again it is good for the patient the more neutrophil which was stored in the bone marrow they will be released in the blood and that will lead to better ability of the body to eliminate the bacteria but if and of course we should not forget that some of these cytokines will go to the hypothalamus and they will disturb temperature regulation center and especially interleukin-1 and tumor necrotic factor when they go to hypothalamus they produce locally in the hypothalamus they produce pg e2 and under the influence of pg e2 prostaglandin e2 temperature center is disturbed and fever start again let me tell you if cytokines are no low concentration infection is less you don't get fever but if there's a lot of cytokines then they will go to the hypothalamus especially interleukin-1 and interleukin-1 will bind with hypothalamic cells and those cells will release pg e2 prostaglandin e2 the prostaglandin e2 which is released within the hypothalamus it will change the temperature regulating center and patient will develop fever patient will develop fever right but if cytokines are produced further yes please yeah i just want to know what receptor is okay oh that's very interesting you want to know that which receptor okay which receptor is present in hypothalamus on which interleukin-1 binds answer is that is called interleukin one receptor okay okay look look it is like this interleukin one first step is interleukin one should bind there and interleukin one will lead to the formation of prostaglandin pg e2 pg e2 will change the here pge2 will change the thermostat in the hypothalamus for example it will give the order for shivering so shivering so person will produce more temperature and it will produce cutaneous vasoconstriction so that more temperature is produced but temperature if heat is not lost so patient temperatures start going up am i clear how the fever is produced endoleucine 1 binds to the hypothalamic cell the local cell produce pge2 pge2 can alter the temperature regulating center in such a way that hypothalamus give the order to the body to shiver so there's more heat production and there's less heat loss because there's cutaneous vasoconstriction right so more heat production less heat loss fever will be there am i clear now but in some patient concentration of in some patients concentration of cytokines become very heavy now i'm making them red cytokines become very dangerous when their concentration become very heavy number one cytokines damage the endothelial cells a lot in high concentration internal endothelial gas form lot of nitric oxide is produced a lot of platelet activating factors are produced severe vasodilation occur all over the body and severe vasodilation occur now it's going to be a shock the blood pressure starts falling blood because all the body vessels dilate dangerously so peripheral pooling of the blood occur because blood is abnormally distributed in the body and because blood is too much distributed and the pooled and the peripheral vasculature so effective venous return is not there cardiac output drop and patient goes into shock like situation so now we'll see patient is entering into septic shock right so there is massive visual dilatation and this relation is by the nitric oxide which is produced by the cytokine action and lipopolysaccharide action with that platelet activating factors are also actively released and which produce generalized inflammation wide spread multi organ inflammation because platelet activating factor control every step of acute inflammation literate activating factor can lead to endothelial activation increased permeability platelet activating factor can activate neutrophils and macrophages platelet activating factor can augment almost every step of acute inflammation and nitric oxide leading to massive viso dilatation in the body is that right meanwhile some of these of course many many blood vessels right in which when platelet activating factors are active those blood vessels may undergo a process of dic small blood vessels disseminate intravascular coagulation their coagulation process is activated in massively in all over the body right and that may also what will happen that lot of platelet activating factor and activated endothelial cells they activate the coagulation system now when if i'm the patient all my body coagulation system is activated i say that it's disseminated intravascular coagulation but when coagulation system is activated all the coagulation factors are consumed suddenly plasminogen converts into plasmin and plasma start breaking down the fibrin so all the fibrin which was made due to coagulation all that fibrin breakdown and suddenly in the blood fibrin breakdown product become more and patient develop anticoagulant state so patient passes through two stages first pro coagulant stage and then anticoagulant again listen white supply activation and damage to endothelial cell and lot of platelet activating factor everywhere coagulation process start all the correlation proteins are consumed and a lot of fibrin is produced then anticoagulant system is activated and all the fibrin is broken down into vibrant breakdown products and after that do you think blood has any more available coagulation factors no all the coagulation factors have been consumed that is why other name for dic is coagulation factor consumption coagulopathy so all correlation factors have been consumed and now body does not have antique uh pro coagulant system so persons start bleeding from multiple sites from iv line patient will bleed from wounds you will bleed maybe from nose you will bleed from mouth your blade so some patient will start bleeding from multiple area and we say that they have developed the i say right one more way more thing which happens in this patient is that lot of cytokines activate the endothelial cells in pulmonary circulation you know this is pulmonary circulation endothelial cells and pulmonary circulations are too much activated and injured a lot of neutrophils and macrophages are stuck there and they start damaging the pulmonary structure and lungs develop severe dysfunction and this condition is called yes what is it called ar ds adult respiratory distress syndrome and here was vaso dilation that is why it is warm shock so massive visualization risk of dic and there's a high risk of a rds adult respiratory distress syndrome person dwells we are distressed in respiratory system due to massive damage to micro circulation of the lung as lot of endothelial activation occur in micro circulation lot of neutrophils and macrophages are activated there and the sphere down by two micro circulation of lung as well as alveolar structure right we call this condition and in the end what will happen that very high concentration of cytokines does not only produce visualization you should not forget to mention that very high concentration of cytokines also inhibit act as a cardio suppressant so we can talk about these cytokines in three waves three stages low on low amount of cytokines moderate amount of cytokine then high amount of cytokines again let me repeat in low amount of cytokine just activate local white cells and local endothelial cell and complement activation it is all good to remove the bacteria in moderate amount of cytokines systemic effects start that acute phase reaction proteins are produced from bone marrow what is released neutrophila release and fever starts in very high concentration of endotoxins and very high concentration of uh cytokines then the real problem start that massive production of platelet activating nitric oxide factor and other cytokine massive visibilitation cardiovascular system collapses right high risk of dic and ards is also there so eventually what will happen to these patients when blood pressure will keep on falling is that right and eventually they will die off septic shock but before the death there is because blood is pulled in the peripheral area and blood heart is not receiving any venous return to produce significant cardiac output so multiple organs develop severe ischemia due to hypoperfusion so multi-organ failure start what is the term used multi-organ failure start central nervous system fails liver fails kidneys fail so multi organ failure start one thing which i want to mention more that in some septic shock right this was something about endotoxemia but some gram positive organism and some fungi also have some molecules like endotoxin not exactly androtoxins but some gram positive bacteria and some fungi have similar molecule to endotoxin and they can also produce the effects like this and patient may go into septic shock you know endotoxins are typically produced by gram negative but some gram positive and some fungi do have some molecule which have action like endotoxin but they are not endotoxin structurally not endotoxins so gram positive bacteria and fungi can also produce septic shock like this this is one thing second thing that some bacteria produce a special type of antigen which is called super antigen some bacteria produce a special antigen which is called super antigen what is the function of super antigen super antigen can activate many many group of lymphocytes usually usually a normal antigen activate a one specific type of t cell but super antigen can activate many different type of t cells what really happen that if there is super antigen super antigen will produce super antigen will produce activate lot of macrophages and lot of t cells right because super antigen has a capacity to cross link the macrophage on one side super nitrogen can hold the macrophage on one side hold the t cell on the other side and super activate both of them so what will happen if super antigens are released in my body due to bacteria super antigens will activate lot of macrophages lot of t cells and all the macrophages and t cell will release lot of cytokines and again picture like this can be produced is that right the classical example of this is toxic shock syndrome toxin you know toxic shock syndrome toxin this toxin is produced by this is not endotoxin this is exotoxin toxic shock syndrome toxin is produced by staphylococcus how it was discovered that in america they found there were some young females who died suddenly developed rash and very rapidly they developed these young females develop hypotension and then they died with multi-organ failure they were not understanding what's wrong with them then they came to know these females were using intravaginal tampons and these tampons were having special type of staphylococci which produced toxic shock syndrome toxin and those staphylococcus from the tampons they release lot of toxin in these females blood and these toxic shock syndrome toxin activate lot of endothelial cell activate lot of macrophages because this is super antigen not endothelial cell they produce activate a lot of macrophages lot of lymphocytes when in these females a lot of macrophages are activated a lot of lymphocytes are activated the massive release of cytokines and that will produce rashes and that will produce cardiovascular collapse and multi-organ failure and death is it clear one thing which is important that how do you investigate this patient right again never forget even though these are the patient in shock the peripheries will be cold or warm they will be warm usually but they are not as cold as it happens what hypovolemic shock but still you should remember some of these patients do have hypothermia is that right anyway uh in the bottle investigation what you will do in the libor investigation you will find neutropenia but more commonly neutrophilia right fifty percent of these patients have destruction of platelets so fifty percent of patient and septic shock have thrombocytopenia about three percent of these patients have coagulation abnormalities and now become the most important investigation if you suspect septic shock you have to rush up for the treatment but if possible you must take three blood samples for the culture for three different veins in a very short time you should take three blood samples from three different veins in a very rapid succession in a short time and send it to the laboratory for the culture and then give the anti-microbial cover is it clear will not go to the management of this the management of this will be discussion and medicine classlessness