Hemodynamics Disorders PDF

HEMODYNAMICS DISORDERS LDCU-BSMLS l GENPATH l TRANSCRIBED BY HAGAR GRACE  Venous end, there is what we...

HEMODYNAMICS DISORDERS LDCU-BSMLS l GENPATH l TRANSCRIBED BY HAGAR GRACE  Venous end, there is what we call oncotic or osmotic pressure that will try to pull water out and into the intravascular compartment So that's the interplay between the hydrostatic pressure and the oncotic pressure and as i mentioned in the capillary level these forces tries to even out, they're about equal 1. Hemodyna,ic Disorders 2. Thromboembolic Disease 3. Shock So our discussion will focus on three aspects:  One is your Hemodynamic Disorders which is the behavior of water across compartments and to a certain extent blood. We have Congestion hyperemia Fluid dynamics is governed by several forces in the blood  The second portion of the topic we'll discuss on vessel wall intravascular volume. To simplify the equation, it is Thromboembolic Disease we all know that in the blood basically the balance between hydrostatic pressure and vessel there is hemostasis and if there is disturbances it oncotic or what we call osmotic pressure may lead to clotting of the blood  And finally the third aspect is the discussion on shock this To simplify the concept it is just basically the pulling and is basically circulatory collapse pushing forces in the blood vessel So what will happen if there is inadequate blood flow to the For example this hydrostatic pressure actually is the pushing different organs of the body? So the topic is divided into five force, it tries to push the water out of the blood vessel so this segments and this particular segment we will discuss on is in the arterial end. On the other hand in the venular end edema, hyperemia, and congestion there is what we call pulling forces so water from the interstitial space are pulled into the intravascular volume and this is called oncotic or osmotic pressure OVERVIEW At the level of the capillaries this hydrostatic and oncotic 1. Edema pressure or what we call pulling and pushing pressures are 2. Hyperemia (Increased flow) even out, they balance each other so, this will enhance the 3. Congestion (Increased backflow) exchange of nutrients oxygen you and carbon monoxide at the 4. Hemorrhage (extravasation) level of the capillaries 5. Hemostasis (keeping blood as fluid) 6. Thrombosis (clotting blood)  Fluid exits the arterial vascular compartment 7. Embolism (downstream travel of a clot) because of hydrostatic pressure pushing it out 8. Infarction (death of tissues w/o blood) 9. Shock (circulatory failure/collapse)  Fluid returns to venous vascular compartment because of oncotic (osmotic) pressure pulling So to give you an overview: back in Edema is the word or the term used to describe an increase of fluid into extracellular compartment so there's an increase in  At the capillary level, the pushing forces are fluid in the extracellular compartment and most likely it is in about equal to the pulling forces the interstitial space REMEMBER: Hyperemia is the term used to describe an increase in blood  Hydrostatic pressure is your pushing pressure and in the flow while congestion on the other hand there is an increase in arterial end it tries to push no water out of the the backflow so hyperemia describes an increase in blood intravascular compartment blood flow in the arteriolar end while congestion describes an increase or there is a increase in the backflow at the venus end All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease Hemorrhage is basically extravasation of blood. It is always  EFFUSIONS, ASCITES, ANASARCA considered abnormal because the circulatory system is closed. So you can only find blood within the intravascular As we all know that 60 of the human body is composed of compartment if it goes out of the intravascular compartment water and two thirds of this is found within the cells. So the that is hemorrhage majority of fluid or water in the human body are actually seen inside the cells. The rest no one third is found outside the cell-- Now, we all know that we have to keep the blood flowing in extracellular the intravascular space or compartment and that's what we call hemostasis So edema occurs when there is a sheath of the water into the interstitial space and there are actually several terminologies Now there are certain conditions that can cause clotting of concerning edema: blood so there is what we call thrombus formation. So we will  so we can have what we call Hydrothorax. So hydro just discuss what are these conditions that will promote means water so water filling in the thoracic cavity is thrombosis called hydrothorax same with hydropericardium so there is water inside the pericardial space or pericardial cavity On the other hand embolos is usually you know when clotted  Effusion is the term given to the accumulation of fluid in blood is detached from the thrombus. From the adhered blood body cavities. So that is the general term of fluid vessel it will detach and travel across the blood vessels it will accumulating in the body cavities essentially be called an embolus however later on you will  Now if that cavity involves the peritoneum you know that realize that clotted blood is not the only one that can behave accumulation of water or fluid for that matter is now as an embolos called ascites so presence of water in the peritoneal cavity is called ascites Infarction is basically death of tissues due to lack of blood. So  A generalized edema you know is called anasarca so here there is what we call hypoxia, in the blood there is there is accumulation of fluid in the soft tissues in the delivery of oxygen so in the absence of adequate blood flow body cavities that is called anasarca, a generalized form there is a decreased delivery of oxygen and this will cause of edema cellular hypoxia. So if the tissues don't have adequate perfusion they will lack oxygen they will eventually cause death to the cells. So that is your infarction And lastly your what we call shock, now this is basically a circulatory collapse in this case there is lack of perfusion to the different organs of the body EDEMA -increased in extracellular fluid. ONLY 4 POSSIBILITIES!!!  Increased Hydrostatic Pressure  Reduced Oncotic Pressure  Lymphatic Obstruction So here we can actually compartmentalize where you find  Sodium/Water Retention water. So in the body water takes up 60 percent of the body weight that is equivalent to about 40 liters in an adult human. now to give you an idea regarding the behavior of water let us Now two-thirds of that that's about 25 liters two-thirds is discuss where you found water in the human body found in the intracellular space so within the cells. WATER One-third is outside the cells and this compartment is further  60% of body subdivided into the  2/3 of body water is INTRA-cellular 1. interstitial space  The rest is INTERSTITIAL 2. intravascular volume  Only 5% is INTRA-vascular As you can see fluid found in plasma or inside blood vessels are  EDEMA is SHIFT to the INTERSTITIAL SPACE the least of the different compartments that's only about three liters of the total 40 liters in the body. Now when you say  HYDRO- edema there might be a fluid coming from the blood vessel  THORAX, -PERICARDIUM, All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease going into the interstitial space or there would be fluid that II. REDUCED PLASMA ONCOTIC PRESSURE goes out of the cell into the interstitial compartment so that is (HYPOPROTEINEMIA) edema  Protein-losing glomerulopathies (nephrotic syndrome)  Liver cirrhosis (ascites)  Malnutrition  Protein-losing gastroenteropathy On the other hand, water will stay more in the interstitial space because they cannot be pulled in so the water cannot be attracted into the blood vessel because of the reduced oncotic pressure. So this is what we call your pulling forces so water from the interstitial space will no longer be pulled into the intravascular compartment because the pulling pressure is quite low Now this oncotic pressure, the pulling forces as we say is actually due to the presence of plasma proteins. So these Okay so another presentation on the relative amount of water plasma proteins are the one that exert this oncotic pressure, it or fluid in the body. will attract water to go inside the blood vessel  So as I mentioned the vast majority are inside the cells that's two thirds. So if you are low in this plasma proteins, the oncotic pressure  One third are found outside the cells so forty percent of will be low so water will tend to stay outside the blood vessel body weight water is found inside the cell they are not pulled in  fifteen percent in the interstitium  and the least amount is found actually in the blood Most important plasma protein is of course your albumin I. INCREASED HYDROSTATIC PRESSURE So any diseases that will cause a reduction of your proteins in  Impaired venous return the blood will cause or will cause or have an effect of low  Congestive heart failure oncotic pressure  Constrictive pericarditis  Venous obstruction or compression So if you have malnutrition, liver cirrhosis or you lose proteins  Thrombosis in the kidney. If you measure your albumin for example or your  External pressure (e.g., mass) total proteins in the blood it will become low because your  Lower extremity inactivity with prolonged kidney is not really filtrating very well. It will lose proteins in dependency the urine  Arteriolar dilation  Heat Same with your protein losing gastroenteropathy you will not  Neurohumoral dysregulation absorb proteins in your intestines. So the end effect here is that you have very low protein levels in the blood. So if you do So again the movement of water is based on the forces. Now a laboratory the effect is hypoprotinemia so in this case anything that would increase the hydrostatic force or your pushing forces will cause an increase of fluid into Albumin is the most abundant protein in the blood the interstitial space. So for example in the inside a blood vessel. Now if there is an increase in hydrostatic pressure it will tend to push water out of the blood vessel so just like in congestive heart failure or in arteriolar dilatation These things know your congestive heart failure, thrombosis, external pressure, arteriolar dilatation, heat, neurohumoral dysregulation will actually tend to increase your hydrostatic pressure so this is your pushing pressure it will promote water out of the blood vessel and into the interstitial space All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease So here as i mentioned in the arteriolar end the pushing forces So this is what happened in elephantiasis will tend to predominate so it will try to push water out of the 1. now we have a worm filarial worm that inhabits your blood vessel lymphatic vessels. The presence of your filaria will cause inflammation In the venous and the pulling forces predominates so the net 2. they will call they will bring in fibrosis effect here is that water from the outside of the blood vessel 3. and it will cause blockage of the lymphatic channel like your interstitial compartment will be pulled in and this 4. so a blockage will cause an increase in pull pushing force pulling forces are governed by the presence of your plasma which will eventually drive water away you know outside proteins. So if you have low plasma proteins, low albumin, this into the interstitial space forces will become weak so it doesn't have enough pulling 5. and even has now manifested as edema power to have water go back inside the blood vessel IV. Sodium [Na+] retention III. LYMPHATIC OBSTRUCTION (LYMPHEDEMA)  Excessive salt intake with renal insufficiency  Inflammatory  Increased tubular reabsorption of sodium  Neoplastic  Renal hypoperfusion→Increased renin-  Post-surgical angiotensin-aldosterone secretion  Post-irradiation The fourth mechanism that will cause edema is sodium. There The third mechanism of edema is lymphatic obstruction so is a dictum in physiology: where sodium goes water follows anything that can block the flow of lymph tissue or lymphatic tissue fluid, flow of tissue fluid inside the lymphatic vessels will In the body the sodium is actually being managed by the cause lymphatic obstruction and the tissue fluid will now go kidney so anything that can cause kidney failure will tilt the out of the lymphatic vessels balance of how we manage sodium so it's no wonder in patients with renal failure they will manifest edema because in So any conditions that will promote this lymphatic obstruction renal failure your tubules can no longer reabsorb sodium will tend to cause edema so whether it's caused by  Inflammation INFLAMMATION  presence of tumors  Acute inflammation  or the lymphatic vessels are destroyed during surgical  Chronic inflammation operation  Angiogenesis  or during radiation therapy So any mass tumor, whatever that can block the vessel you know will cause an increase in the pushing force so this will now cause fluid particularly water out into the blood vessel Now inflammation as I mentioned can cause edema. We have discussed it in our previous topic that inflammation can bring in edema and this is due to the opening of the gaps in the endothelial lining of the blood vessel wall so inflammation will promote edema So this is what happened when you have pneumonia in the lungs so you have now inflammation brought about by the presence of microbes and this will now open up the endothelial lining forming gaps and water will now go out All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease Now of course this type of fluid in inflammation is an exudate Another cause of accumulation of water this time in the because not it is not only water that can go out but includes peritoneal cavity is your portal hypertension cellular substances other plasma proteins can even go out that's why it's called an exudate So in this case there is a built up of pressure in the portal system like what happened in Schistosomiasis. This increase in CHF EDEMA portal hypertension will cause water to get out of the blood  INCREASED VENOUS PRESSURE DUE TO FAILURE vessel and into the peritoneal cavity  DECREASED RENAL PERFUSION, triggering of RENIN- ANGIOTENSION-ALDOSTERONE complex, This is also what happened when there is hypoalbuminia as we resulting ultimately in SODIUM RETENTION all know albumin is the largest constituent of your plasma proteins. A decrease in plasma proteins will skew the balance Another one is when you have congestive heart failure so here towards the less water that is pulled in because albumin is the your heart failed as a pump so what happened there is main plasma proteins which in turn is the one that is increased venous pressure because of the backflow. Now responsible for your oncotic pressures because the heart is not pumping very well so there will be a buildup of uh venous pressure and if you have a left-sided RENAL EDEMA heart failure the build-up will actually occur in the lungs so you  Sodium retention can actually have pulmonary edema in congestive heart failure  Protein Losing Glumerulopathies (Nephrotic Syndrome) Now since uh the heart is not pumping blood very well, the cardiac output is quite low and this will now cause a signal to Another cause manifestation of edema is due to renal causes the organs particularly the kidney. Because of less perfusion so we have your sodium retention. Sodium actually attracts the kidney will perceive this, it is not receiving adequate blood water so where sodium goes water follows. So if your kidneys supply. The kidneys by the way receive 20 percent of the retain sodium, if there is now a abundant sodium in the body cardiac output, if it receives less than 20 it will trigger your in a particular compartment water will go to that Renin-Angiotensin- Aldosterone Axis (RAAS) this will eventually compartment. So if there is a lot of sodium in the blood you cause your kidney to conserve sodium know it will attract water inside the blood vessel so water will pull inside the blood vessel so there's a build up of water in the intravascular space. That's what happened in hypertension because if you notice in persons with high blood pressure, they will reduce the intake of sodium because where sodium goes water follows SUMMARY EDEMA  SUBCUTANEOUS ("PITTING")  "DEPENDENT"  ANASARCA  LEFT vs RIGHT HEART  PERIORBITAL (RENAL)  PULMONARY So here we illustrate that for example you have left-sided  CEREBRAL (closed cavity, no expansion) heart failure there will now be built up of water here in the  HERNIATION of cerebellar tonsils pulmonary veins and this pressure will be transmitted towards  HERNIATION of hippocampal uncus over the lungs. Now because water will build up here and in the tentorium lungs water will tend to go into the alveolar spaces. So we will  HERNIATION, subfalcine now have what we call pulmonary edema. So water will now go to this alveolar spaces filling the alveolar sucks with water. So the edema can be manifested in the subcutaneous tissues So water in the presence of water in the alveolar space will in the dependent areas of the body. So this edema will tend to actually hinder the exchange of gases: oxygen and carbon accumulate in the lower extremities in the feet particularly monoxide that is why pulmonary edema can be manifested as difficulty of breathing So as I mentioned if there is a generalized edema it is called ANASARCA HEPATIC ASCITES  Portal Hypertension  Hypoalbuminemia All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease Okay so we already mentioned edema caused by the kidney So these three areas are very vulnerable for for herniation in abnormalities cerebral edema. If you can see the brain has no adequate space to expand if there is cerebral edema It can accumulate in the lungs if you have congestive heart failure but the most harmful or deadly consequence of edema is in the brain TRANSUDATES VS. EXUDATES The brain is enclosed in a bony cranium so brain is soft Transudate Exudate compared to the skull so if there is edema in the brain there is results from disturbance Exudate results from very little room for expansion it cannot overcome the very of Starling forces damage to the capillary hard skull. So what happened to the soft brain it will now wall cause hernation and this can cause death so cerebral edema is specific gravity < 1.012 specific gravity > 1.012 actually very harmful protein content < 3 g/dl, protein content > 3 g/dl, LDH low LDH high So as i mentioned in hemodynamic disorders The shift of fluid from one compartment to another is a transudate Because this results from the disturbance of the starlings forces. Now you're pulling and pushing forces hydrostatic pressure and oncotic pressure since only fluid will move across compartments there is  no plasma proteins  no cellular material  so it has a very low specific gravity  low protein content So here we can see the pitting edema. When you put pressure  low LDH on the subcutaneous tissue you can actually see the indentation. Now that is what we call pitting edema so there Unlike what happened in inflammation, the edema is due to is a lot of fluid in the interstitial space in the foot so this is a the opening up of the endothelial cells and aside from water independent area there are other things that go out of the blood vessel so your plasma proteins, your blood cells. So it inflammation, the one that cause edema is a an exudate. Unlike in your hemodynamic disorders in edema where it is a transudate HYPEREMIA (CONGESTION) Here is the vulnerable rejoins found or are seen in the brain when there is cerebral edema. 1. So near the cingulate gyrus in the frontal lobe it will cause torsion of the portion of the brain that is what we call herniation 2. Another vulnerable area is in the hippocampus. This one will impinge on the midbrain in the hippocampus 3. and the third one is in the cerebellum where it will So hyperemia in the arteriolar and so this is your small arteries. impinge on the lower brain stem. The lower brainstem An increase in blood flow in the arteriolar end is what we call houses the the area for your respiration All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease hyperemia so increase in the blood flow at the arteriolar end So this is manifested as erythema. This has happened during  exercise  during inflammation  another manifestation is your blushing in embarrassing moments you feel that your face red dense  also at times in when you drink alcohol there is vasodilatation in the blood vessels in your face so there will be redness in your face On the other hand if there is a decrease in the outflow so at the venous end there might be obstruction or blockage there will now be pulling of blood in the venous end so this is what we call congestion and it is not really red or pink color because So in acute passive congestion for example in the lungs. So we the blood here is deoxygenated blood have again fluid in the alveolar spaces if there is a congestion in the lungs it can occur acutely or it can occur chronically So the manifestation here is that it looks like there's cyanosis black blue because the blood that is pulled in the venous end is no longer filled with oxygen so it's a deoxygenized blood Hyperemia arteriolar end; Congestion is at the venus end HYPEREMIA ACTIVE PROCESS CONGESTION PASSIVE PROCESS; Acute or Chronic So since dilatation of your arteries is an active process so that is your hyperemia and since congestion is a a passive process So this can be manifested in an x-ray when there is increase in because only the blood will pull at the venus end there's no the lines not peripheral lines or what we call kelsey's lines and actual dilatation. Dilatation at the venous end is due to the this is a characteristic of your pulmonary edema accumulation of the deoxygenated blood so it's a passive process CONGESTION LUNG Acute Chronic LIVER Acute Chronic CEREBRAL Okay so again congestion can occur in different organs of the body can occur in the lung, the liver, and of course in the brain So if you look at also in the costophrenic angles there might be accumulation of fluid you know and that is your plural effusion All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease Or it can occur there's chronic passive congestion in the lungs when there is a heart failure so the heart failure is a long time As I mentioned in the brain there can be also be congestion coming and this will cause flattening of the gyrus and as I mentioned the harmful effects here if there is cerebral edema is that it And what happened here is that, again the blood will will be prone to herniation which is quite deadly accumulate in the alveolar space because of the increased pressure in the pulmonary vessels the small or the thin walls of the blood vessels in the veins (venular part) will rupture and HEMORRHAGE blood can again squeeze through the alveolar spaces  EXTRAVASATION beyond vessel Now this blood will be taken up by your macrophages that is  “HEMORRHAGIC DIATHESIS” why in a person who died with congestive heart failure when  HEMATOMA (implies MASS effect) you look at the lungs there are so many hemosiderin  “DISSECTION” macrophages that will take up their blood cells so they are  PETECHIAE (1-2mm) (PLATELETS) filled with hemosiderin pigments that is why these  PURPURA 1cm (BRUISE)  HEMO-: -thorax, -pericardium, -peritoneum, HEMARTHROSIS  ACUTE, CHRONIC First of all we discuss on hemorrhage and as I mentioned in the previous segment hemorrhage is abnormal because the circulatory system is supposedly a closed system and blood should not get out of the blood vessel so any extravasation of blood beyond the confines of the blood vessel is called hemorrhage. When this hemorrhage behave as a mass lesion meaning when they occupy space they are technically called hematoma There are a lot of manifestations on hemorrhage:  this very small you know rushes manifestations include Now congestion can also occur in the liver so here in this case your petechiae; very small 1 to 2 mm millimeters if you have a right-sided heart failure blood will pull in the  a little larger than petechiae is your purpura right side of the the heart into your in blood vessels that feed  and large areas with hemorrhage more than one your vena cava and into your liver. So there will now be centimeters is called ecchymoses. So this is what we call congestion in the liver and these are your central veins which bruise. appeared very you know distended with blood  Now finding of blood in the thorax is called hemothorax. So if you look at if you take a sections of that liver you can So this is a distinction from your hydro---hydrothorax actually see the congestion occurring in the central veins of means water; hemo means blood so hemothorax is the liver so this is a passive congestion in the liver accumulation of blood in the thoracic cavity  Similar to those in hemopericardium so again blood in the pericardial space  Or even in the peritoneal space in this case it will be called hemoperitoneum  So blood in the joint spaces is called hemarthrosis All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease Blood may accumulate in an area--acute then there will be; it  epi above the dura will become chronic so there will be a transition on the quality  subdural sub means down or under so under the dura of the blood as we will see Usually the: EVOLUTION of HEMORRHAGE  epidural usually follows skull fracture and  ACUTE CHRONIC  subdural hematoma usually follows close head trauma  PURPLE→ GREEN→ BROWN  Hemoglobin→ Bilibrubin→ HEMOSIDERIN Nevertheless the accumulation of blood may have harmful effects because it will impinge especially in subdural So there is an evolution of hemorrhage. Now from acute to hematoma it will cause a mass effect that can distort the chronic so blood may be manifest as red brown becoming underlying brain green and eventually becoming brown this reflects the pigment that is found in blood HEMATOMA vs. "CLOT"  Pre-mortem clots have texture and usually So from hemoglobin it will be transformed into bilirubin and ADHERE to a vessel wall. eventually become hemosiderin. So this characteristics is  Post-mortem clots have a jelly or chicken fat actually taken seen in forensic medicine when they try to get consistency. the timing of lesion where how many days are the lesion there so this helps in the evolution of hemorrhage through the So what's the difference between hematoma versus clot? change in the type of pigments through time  In a premortem class meaning buhang pa yung tao actually clot is adherent to the blood vessel wall  while clotted blood after death usually are very soft and have a jelly chicken fat consistency HEMOSTASIS  OPPOSITE of THROMBOSIS  PRESERVE LIQUIDITY OF BLOOD  "PLUG" sites of vascular injury THREE COMPONENTS  VASCULAR WALL  PLATELETS  COAGULATION CASCADE Blood can occur anywhere so it can be seen in the skin but, of course it can be seen in the internal organs and the identification that there is bleeding in the organs can be life- One important or fundamental aspect on blood is that it saving if detected early should be in a liquid state Of coursevthere is thrombosis when needed and this thrombose formation is usually needed  when there are vascular injury  and this thrombus is used to plug the blood vessel injury So it is only at this point that presence of thrombus is quite useful. Otherwise blood should be preserved in its liquid state and that is what we call hemostasis To achieve this hemostasis there are three important factors or participants: the vascular wall. the platelets, and coagulation cascade One of the more harmful manifestations of hemorrhage is when it occurs in the head. So we have what we call epidural SEQUENCE of EVENTS following VASCULAR INJURY hematoma or subdural; it depends on the location dura is one  ARTERIOLAR VASOCONSTRICTION of the layers of your meaninges-- covering of your brain  Reflex Neurogenic  Endothelin, from endothelial cells All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease  THROMBOGENIC ECM at injury site IN INJURY  Adhere and activate platelets  Pro-coagulant properties  Platelet aggregation (1° HEMOSTASIS) Normally the endothelium has anti-platelet properties, it has  TISSUE FACTOR released by endothelium, plts. anticoagulant properties, and also fibrinolytic properties  Activates coagulation cascade→ thrombin because as I mentioned these players also have to maintain →fibrin (2° HEMOSTASIS) hemostasis meaning the liquid nature of the blood  FIBRIN polymerizes, TPA limits plug However in injury the endothelium will secrete pro-coagulant properties. Now this pro-coagulant properties will now trigger Following vascular injury; the coagulation cascade which forms thrombin and eventually 1. the blood vessel will react. In this case the first reaction is fibrin your vasoconstriction 2. and the injury will cause exposure to the sub-endothelial matrix and this is what we call this exposure of the sub endothelial matrix is actually thrombogenic. 3. It will cause platelets to activate and adhere to each other so there is now what we call platelet aggregation because the platelets are recruited to plug the damage area 4. This plug is called primary hemostasis. It is considered a soft blood because it is composed mainly of platelets 5. To make this primary plug stronger there the endothelium which is at this point injured and the platelets will now produce what we call tissue factor 6. This tissue factor will now activate the coagulation Here normally, there's an intact blood vessel so blood is in the cascade. This will now result in thrombin formation. usual liquid state and when there is injury the underlying sub 7. This thrombin will up will now go on to form fibrin endothelial matrix will be exposed and the endothelium will 8. and this fibrin polymerizes the platelet plug--makes it now secrete tissue factor which is actually thrombogenic more durable and makes it quite hard 9. Eventually this secondary plug, as we now call it, because ANTI-Platelet PROPERTIES it is acted upon by fibrin make it stronger it will  Protection from the subendothelial ECM eventually lysed so that repair and healing will proceed  Degrades ADP (inhibit aggregation) Again when the blood vessel wall is already repaired, the fibrin ANTI-Coagulant PROPERTIES plug or what you call secondary plug will be lyse. So that's  Membrane HEPARIN-like molecules that's how blood vessels react to vascular injury  Makes THROMBOMODULIN→ Protein-C  TISSUE FACTOR PATHWAY INHIBITOR PLAYERS  Endothelium FIBRINOLYTIC PROPERTIES (TPA)  Platelets  Coagulation “Cascade” Normally the endothelium as I mentioned has anti-platelet properties Now these same players again will now also participate in  so it degrades ADP which inhibits platelet aggregation thrombus formation other than those intended to repair and vascular injury. So in this case this is now pathologic or The endothelium also has anticoagulant properties because it abnormal because the thrombus formation is not in response  secretes heparin like molecule to the blood vessel injury  it secretes tissue factor pathway tissue factor inhibitor  it makes thrombomodulin which is used for synthesis of protein c which is anti-thrombin. Pprotein c has anti- ENDOTHELIUM thrombin properties NORMALLY And of course endothelium also have what we call fibrinolytic  Antiplatelet properties properties  Anticoagulant properties  Fibrinolytic properties All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease PROTHROMBOTIC PROPERTIES and becomes activated and together with your endothelium  Makes vWF, which binds Platelets→Collagen your platelets also produce tissue factor  Makes TISSUE FACTOR (with platelets)  Makes Plasminogen inhibitors However in injury, endothelium will also be prothrombotic. It will produce substances that eventually participates in thrombus formation so the endothelium has a lot of properties Normally it doesn't, it has hemostatic functions but when injured it enhanced formation of thrombus and this is due to the Von Willibrand factor and this Von Willibrand factor actually binds platelets to the sub endothelial matrix The the endothelium also produce a tissue factor together with the platelets which again enhance thrombin formation and of course it also has plasminogen inhibitors So in this case there is vascular injury and this vascular injury So all this makes the endothelium at times of injury pro will now attract the platelets to be activated, they adhere to thrombotic--- it enhanced thrombus formation each other and eventually they will form a plug on the site of the endothelial injury. So this is what we call the primary hemostasis PROTHROMBOTIC PROPERTIES OF ENDOTHELIUM  Activated by Infectious agents  Activated by Hemodynamics PLATELET PHASES  Activated by Plasma  Adhesion  Secretion (I.e., “release” or “activation” or Now this pro-thrombotic properties of the endothelium can be “degranulation”) activated by  Aggregation  infectious agents  disturbances in the blood flow Platelets will adhere to one another, they secrete or release  and of course by plasma okay the substances found in the granules, and they will aggregate or attracted to each other forming a what we call platelet plug So this makes the endothelium a double edged sword again because when these factors: infectious agents, disturbances in PLATELET ADHESION hemodynamics or blood flow, and plasma. Now there are substances this will now enhance thrombus formation which is actually pathologic  Primarily to the subendothelial ECM  Regulated by vWF, which bridges platelet surface receptors to ECM collagen PLATELETS So these steps: the platelet aggregation, segregation, and ALPHA GRANULES adhesion are modulated by several substances  Fibrinogen  Fibronectin For platelet adhesion it is regulated by the Von Willebrand  Factor-V, Factor-VIII factors so this vWF will bridge the receptors in the platelet surface through the extracellular matrix collagen  Platelet factor 4, TGF-beta Now in as I mentioned in the sub endothelial layer this will be DELTA GRANULES (DENSE BODIES) exposed upon injury the vWF will bridge the platelet surface  ADP/ATP, Ca+, Histamine, Serotonin, through this extracellular matrix collagen Epinephrine With endothelium, form Tissue Factor PLATELET SECRETION The second participants are your platelets. So platelets has what we call alpha granules and delta granules, this granules  BOTH granules, αlpha and delta contains a lot of substances that will cause them to adhere  Binding of agonists to platelet surface receptors AND intracellular protein PHOSPHORYLATION All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease Now activate a secretion, it's basically the release of the  Express TISSUE FACTOR substances found in the alpha and delta granules of the  PRIMARY SECONDARY PLUG platelets  STRENGTHENED by FIBRIN PLATELET AGGREGATION  ADP  Thromboxane A2  THROMBIN from coagulation cascade also  FIBRIN further strengthens and hardens and contracts the platelet plug This is followed by platelet aggregation so again this is due to your ADP and your thromboxane a2 so these are substances that will enhance platelet aggregation So this plug, so it will lead to the formation of blood clot which And eventually the platelets together with the endothelium is used to repair the blood vessel wall that is injured will secrete tissue factor. This tissue factor will now stimulate the coagulation cascade which will now form thrombin and Now the same players that participate in hemostasis are also eventually this thrombin will lead to the formation of fibrin the one that participate in thrombus formation not to repair which strengthens this soft platelet plug the injured blood vessel but formation of thrombus which is I emphasize will now be abnormal in a disease condition; pathologic condition because there is blood clot formation COAGULATION CASCADE  INTRINSIC(contact)/EXTRINSIC(Tissue Factor)  Proenzymes→ Enzymes  Prothrombin(II)→Thrombin(lla)  Fibrinogen(1)→Fibrin(la)  Cofactors  Ca++ 1. So here we can see that there is an injury in the blood  Phospholipid (from platelet membranes) vessel wall  Vit-K dep. factors: II, VII, IX, X, Prot. S, C, Z 2. and the platelets are activated to aggregate, adhere to each other The third participant is your coagulation cascade because this 3. and they will now secrete substances that will eventually is the one that will be triggered when there is release of your form a plug. tissue factor 4. So they will aggregate each other and form a plug which is soft plug or what we call primary hemostasis 5. and eventually this plug will become hard or it will be strengthened because the platelet and the endothelial lining will produce tissue factor 6. which will eventually activate the coagulation cascade for formation of thrombin. 7. Thrombin will lead to the formation of fibrin 8. and it is the fibrin that will strengthen the primary platelet plug PLATELET EVENTS  ADHERENCE to ECM  SECRETION of ADP and TXA2  EXPOSE phospholipid complexes All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease So the tissue factor is the one that will trigger the formation of your thrombin and thrombin will now lead to the formation of THROMBOSIS your fibrin. So we all know about the coagulation factor the intrinsic and extrinsic pathways and formation of the thrombin  Pathogenesis and fibrin  Endothelial Injury  Alterations in Flow The one that will enhance the cascade are what we call pro  Hypercoagulability coagulant properties. However there is also actually inhibitors  Morphology in the presence of:  Fate  protein c  Clinical Correlations  protein s  Venous  anti-thrombin  Arterial (Mural)  plasminogen inhibitors that actually inhibit. So in normal body there's a balance of all these things however in a pathologic state there is a balance lost and there might be conditions that lead to thrombus formation COAGULATION TESTS  (a) PTT INTRINSIC  PT (INR) EXTRINSIC  BLEEDING TIME (Platelets) (2-9min)  Platelet count (150,000-400,000/mm3)  Fibrinogen  Factor assays There are laboratory tests that can see if our coagulation system system cascade is functioning very well Thrombosis will occur due to the contributions of these three important things and these are what you call Virchow’s  So your activated protrumbin time checks for your triangle intrinsic pathway.  Your protrumbin time will look at your extrinsic pathway So that's the reason why a person is prone to thrombus  Bleeding time was for once upon a time quite popular; it formation because of this abnormalities contributed by these will check the number of platelets because you can check three factors or these three things: the number of platelet but it's a crude way to measure 1. one is endothelial injury the qualitative aspect of your platelets. Because you can 2. the other one is abnormalities in the flow of blood have an adequate number of platelets but it doesn't 3. and the third one is a hypercoagulability state function very well  but bleeding time there are problems associated with So all these factors will interact with each other and will now bleeding time: uniformity of the procedure cannot be cause an increase in the probability that a formation of this standardized adequately so this bleeding time has been clotting of blood will occur. So these are what we call replaced in modern assays like platelet aggregometry contributors to the abnormal formation of blood clots but not all laboratories are equipped to do platelet aggregometry ENDOTHELIAL "INJURY"  Platelet-count because if you have low number of any perturbation in the dynamic balance of the platelets you cannot form actually a platelet plug so you pro- and antithrombotic effects of endothelium, not will you will be prone to bleeding. only physical "damage"  All we can do fibrinogen assay and individual factor assay so it's it's possible. At this time there are many assays First is your endothelial injury so we all know that that you can assay for vWF, factor VIII, Factor IX, and all endothelium has a pro-coagulant and anti-thrombotic effect other coagulation factors from our last segment. So any disturbances, any imbalance or what we call perturbation of the balance between this pro- coagulant and anti-thrombotic effects of the endothelium will tilt the balance one way or another All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease So it doesn't only mean that there is physical damage to the Another but less common is your deficiency in antithrombin III, endothelium. If there is an imbalance that the pro-coagulant protein C ,and proteinS it's not as common as factor V and effects of your endothelium is quite heavy meaning it will tilt prothrombin the balance to this side because there's an absence of a counter balance from the other side it's between pro And of course any abnormalities in your fibrinolysis which is coagulant and anti-thrombotic effects of the substances that actually very rare. So among these inherited defects in are present in the endothelium coagulation they can be classified into common, rare, and very rare. As i mentioned factor V and prothrombin is or are ABNORMAL FLOW the most common among this inhibited hypercoagulability  NON-LAMINAR FLOW state  TURBULENCE  EDDIES  STASIS  "DISRUPTED" ENDOTHELIUM ALL of these factors may bring platelets into contact with endothelium and/or ECM Stasis, eddies, or any turbulence in the flow of blood will contribute to thrombose formation. So any non-laminar flow of blood will enhance formation of thrombus. In other words any disturbances in the normal streaming of the blood like for example stasis it will slow down, eddies meaning parang whirlpool or any disturbance for that matter. So the flow of blood will become non laminar will actually enhance the formation of thrombus The reason here is that the disruption on the laminar flow of blood will actually bring the platelets into contact with the endothelium and or the extracellular matrix present in the underlying the endothelial lining. So there there will be So where is that factor V and prothrombin? it's actually in the disruption of the endothelium in this case and it will expose last step before formation of thrombin the sub endothelial extracellular matrix wherein there are tissue factors that abounds and we all know that tissue factors So this is your factor V and this is your prothrombin. So can cause your coagulation system to cascade formation of abnormalities in this prothrombin and factor V will cause a your thrombin. So that's the that's the reason why we have to formation of this coagulation cascade keep the flow of blood undisturbed Now your protein c, your protein s, and your anti-thrombin HYPERCOAGULABILITY (INHERITED) are actually inhibitors of your coagulation cascade. So if you  COMMONEST: Factor V and Prothrombin remove the inhibitors there is now a preponderance to have defects this coagulation sequence to proceed and of course the last  Common: Mutation in prothrombin gene, inherited is your fibrinogen which is actually very very rare Mutation in methyltetrahydrofolate gene  Rare: Antithrombin III deficiency, Protein C HYPERCOAGULABILITY (ACQUIRED) deficiency, Protein S deficiency  Prolonged bed rest or immobilization  Very rare: Fibrinolysis defects  Myocardial infarction  Atrial fibrillation There are two forms for this:  Tissue damage (surgery, fracture, burns)  Inherited  Cancer (TROUSSEAU syndrome, i.e., migratory  Acquired thrombophlebitis)  Prosthetic cardiac valves The most common inherited hypercoagulability state meaning  Disseminated intravascular coagulation you are born with it is that you have defect in factorV and  Heparin-induced thrombocytopenia prothrombin. So there's a genetic basis for this a mutation  Antiphospholipid antibody syndrome (lupus perhaps on the prothrombin gene or in your factorV anticoagulant syndrome) All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease Risk for thrombosis: This is a example of a thrombus formation that is obstructive  Cardiomyopathy so it arises from a blood vessel wall that has already have an  Nephrotic syndrome arteromatous block and what is the the remaining lumen is  Pregnancy now occupied by the thrombus. So this is now an obstructive  Oral contraceptive use type of thrombus because the lumen it will compromise the  Sickle cell anemia blood flow because of the absence of the lumen in the blood  Smoking, Obesity vessel. So blood cannot go through cannot pass through. So this is an example of an obstructive form of thrombus Other conditions that cause hypercoaguability state includes cardiomyopathy so there are abnormalities in the heart that FATE OF THROMBI slow down the pumping action of the heart, nephrotic syndrome, pregnancy, use of oral contraceptive pills, sickle cell  PROPAGATION (Downstream) anemia. smoking and obesity are considered risk factors for  EMBOLIZATION thrombus formation  DISSOLUTION  ORGANIZATION  RECANALIZATION MORPHOLOGY Eventually the thrombus may:  ADHERENCE TO VESSEL WALL  Propagate--it will add up more cluttered blood along its  HEART (MURAL) way  ARTERY (OCCLUSIVE/INFARCT)  It may detach so it may become an embolus or it can  VEIN dissolve when there is activation of your fibrinolysis  OBSTRUCTIVE vs. NON-OBSTRUCTIVE  Or it will organize become part of the blood vessel wall  RED, YELLOW, GREY/WHITE  And it can also be recanalized there is formation of small  ACUTE, ORGANIZING, OLD lumen within the thrombus that can make the blood pass through So what does this thrombus uh looks like? So basically thrombus is clotted blood and it adheres to the blood vessel wall and they can be seen:  in the heart  they can be found in the arteries  and they can also be seen in the veins The most important thing to remember that has clinical outcome of a thrombus formation is whether they are obstructive or not So this is an example of propagation that the thrombus add up to its cluttered blood. It will it will fill the lumen and through a segment of the blood vessel; that's propagation so resolution there is the thrombus dissolved and almost get there's no remnantsthat can be seen or it can embolize meaning it will detach from the area of thrombose formation go to other Here is an example of a mural thrombus occurring in the heart organs; it will cause an embolus. As I mentioned it can also and they can be found in the chambers of the heart or it can organize and become part of the wall; it's incorporated into be found in the valves of the heart the blood vessel wall or they can organize but form small areas where blood can pass through so there is recanalization All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease So another microscopic view on the occlusive nature of this platelets, fibrinogen, F-VIII and other consumable thrombus in this case it occurs in the arteries so there is a clotting factors, brain, heart, lungs, kidneys, complete seal off on the blood vessel so blood cannot pass MICROSCOPIC ONLY through anymore. Of course it has a dire consequence to the organ that the blood is supplying There are conditions that we have to watch out like obstetric complications difficult childbirths, advanced malignancy, and of course shock. Disseminated intravascular coagulation is not D.V.T. a primary disease but they are considered complications to this obstretic difficult child birth, in malignancies, and shock.  DEEP (CALF, THIGH, PELVIC) VEIN THROMBOSIS  CHF a huge factor The DIC is a serious condition this is due to consumptive  INACTIVITY!!! coagulopathy and your clotting factors are activated and they  Trauma form thrombus formation in different organs. Because also of  Surgery this consumptive coagulopathy one is also prone to bleeding  Burns so this disseminated intravascular coagulation is quite a  Injury to vessels, serious condition where in bleeding and thrombose formation  Procoagulant substances from tissues are manifested  Reduced t-PA activity In blood vessels like your veins, we have what we call deep EMBOLISM vein thrombosis and this is a quite fairly common occurrence and it is due to inactivity. Usually trauma, surgery, burns, and  Pulmonary there is prolonged immobilization to that lower leg and it will  Systemic (Mural Thrombi and Aneurysms) cause thrombos formation because of the release of pro-  Fat coagulant substances from these injured vessels  Air  Amniotic Fluid ARTERIAL/CARDIAC THROMBI Embolus is any material that can potentially large in the blood vessel and traditionally we think of an embolus as a detached  ACUTE MYOCARDIAL INFARCTION = OLD thrombus. However it turns out that there are other materials ATHEROSCLEROSIS + FRESH THROMBOSIS that can act as an embolus: fat globules, bubbles of air, even amniotic fluid can become an embolus; tumor cells can  ARTERIAL THROMBI also may send fragments become an embolus so it is not only detached cluttered blood DOWNSTREAM, but these fragments may that can act as an embolus contain flecks of PLAQUE also PULMONARY EMBOLISM  LODGING is PROPORTIONAL to the % of cardiac  USUALLY SILENT output the organ receives, i.e., brain, kidneys,  CHEST PAIN, LOW PO2, Shortness of breath spleen, legs, or the diameter of the downstream  Sudden OCCLUSION of >60% of pulmonary vessel vasculature, presents a HIGH risk for sudden death, i.e., acute cor pulmonale, ACUTE right It can also be seen meaning the clotted blood can all be also heart failure be seen in the arteries and in the heart usually in the arteries. They usually are seen in association with an atheromatous Perhaps the most known of this embolism involves the lungs plaque okay so there is prior injury to the endothelium and pulmonary embolism is one of a few cases that can cause because of the presence of this atheromatous plaque. So don't sudden death. It is usually silent, there's no premonition and forget about the Virchow’s triangle that are contributors to you develop chest pain and have shortness of breath and the formation of this blood clots usually the most common source of pulmonary embolism is a thrombus from the deep veins of the legs DISSEMINATED INTRAVASCULAR COAGULATION  "SADDLE" embolism often/usually fatal  PRE vs. POST mortem blood clot:  OBSTETRIC COMPLICATIONS  PRE: Friable, adherent, lines of ZAHN  ADVANCED MALIGNANCY  POST: Current jelly or chicken fat  SHOCK  NOT a primary disease Especially if the embolus is a saddle type of embolus it is  CONSUMPTIVE coagulopathy, e.g., reduced usually fatal and of course we have made a distinction All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease between a blood clot that occurs before death and a blood cut that occurs after death. We all know that the cluttered blood when the patient is still alive is friable but it is adherent to the blood vessel wall. Well in death blood can clot but it is of the soft type with the consistency of a chicken fat or current jelly now it is not adhered to the blood vessel wall. So this blood clots may now go to the other organs because they are detached and in this case of pulmonary embolism they travel from the deep veins of the legs to the lung and it may involve the large blood cells and cause occlude especially along the area where the blood vessels bifurcates and cause significant So this is an example of fat globules and it causes blockage in injury the small blood vessels in the lungs SYSTEMIC EMBOLI  "PARADOXICAL" EMBOLI  80% cardiac; 20% aortic  Embolization lodging site is proportional to the degree of flow (cardiac output) that area or organ gets, i.e., brain, kidneys, legs Embolus can also occur in the systemic like in the arteries and some of the sources of this embolus is your heart that's the most common source of systemic embolus followed by the aorta and these embolus found in the arteries can lodge into the different organs based on the proportional degree of the and here are the squames taken from the fetus and it lodge on flow of the cardiac output. So very vascular organs that again blood vessels of the lungs. So these squames with receive substantial output from the heart-- there is an associated amniotic fluid behave as an embolus increased chance of an embolus so for example the brain receive significant amount of blood coming from the heart so INFARCTION the brain has an increased chance that an embolus will lodge coming from the heart. So patient will manifest like a stroke when these embolus lodge in the smaller vessels in the brain  Defined as an area of necrosis secondary to decreased blood flow OTHER EMBOLI  HEMORRHAGIC vs. ANEMIC  FAT (long bone fractures)  RED vs. WHITE  AIR (SCUBA bends)  END ARTERIES vs. NO END ARTERIES  AMNIOTIC FLUID, very prolonged or difficult  ACUTE--> ORGANIZATION--> FIBROSIS delivery, high mortality The reason why embolus is dangerous is because it can cause As I mentioned earlier it is not only clotted blood that can necrosis so it can block the flow of blood. Embolus may cause occlude or travel through the blood vessels and potentially a decrease in the flow of blood. So it may cause hypoxia to the occlude the bloodstream (flow of the blood) so as i mentioned cells of the organ where the blood supply is compromised  fat especially in long bone fractures may act as an especially if the arteries that supplies the particular area of the embolus organ here are called end arteries (there are no collateral  bubbles of air; that's the reason why deep sea divers are supply of the organ) not advised to arise to the surface of the ocean rapidly because the mixture of gases in the blood may act in INFARCTION FACTORS bubbles may act as an embolus  NATURE of VASCULAR SUPPLY  In childbirth; difficult childbirth there are rare cases  RATE of DEVELOPMENT where in the amniotic fluid you know carrying the  SLOW (BETTER) squames from the baby will penetrate the uterine blood  FAST (WORSE) vessels and lodge into the lungs of the mother and it is  VULNERABILITY to HYPOXIA one of the unfortunate events that cause sudden death.  MYOCYTE vs. FIBROBLAST So it's a obstetric complication and true enough on  CHF vs. NO CHF autopsy you can see the squames that are found in the blood vessels in the lungs of the mother It's the nature of the vascular supply where the presentation can be hemorrhagic or anemic All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease Second is the rate of development of course a fast compromise that the decrease in the blood flow is all abrupt compared to SHOCK those that occur very slowly. So those that are abrupt like what happened in coronary arteries the blockage of the  Pathogenesis coronary arteries of the heart--you can have sudden heart  Cardiac attack if the rate of development of the blockage abruptly  Septic occur at a very fast rate.  Hypovolemic  Morphology Of course the result can also be dependent on the type of cells  Clinical Course there are three cells that are quite vulnerable to hypoxia and these are your: Shock is a very serious condition it is basically manifested as 1. cardiac cells loss of tissue perfusion. So in this case there is a collapse in the 2. renal tubular cells circulatory system such that there is a lack of blood flow to 3. neurons (brain cells) important organs. So this lack of blood flow will cause hypoxia (lack of oxygen) to these organs so what happens the cells So compared to your cartilage, your smooth muscles, your becomes dysfunctional and it could possibly damage the straighted muscles, fibroblasts these three cells are very very organs. As a result it may cause the organ to fail in its function vulnerable to episodes of hypoxia. Hypoxia means decrease oxygen so when there is a compromised blood flow there is Definition: also a corresponding decrease in the supply of oxygen. So this CARDIOVASCULAR COLLAPSE leads now to what we call infarction (death of tissues due to loss of blood supply) Common pathophysiologic features:  INADEQUATE CARDIAC OUTPUT and/or  INADEQUATE BLOOD VOLUME In medical parlance, shock is what we known as cardiovascular collapse. As i mentioned there is inadequate perfusion of the different organs so there is failure of your cardiovascular system and this failure is manifested in two conditions: 1. one is there is inadequate cardiac output meaning the blood is not pumping blood that will satisfy the needs of the different organs So this is an example in the lungs where there is necrosis in a 2. or if the blood there's no problem with the heart particular area supplied by a small blood vessel. So either the pumping the blood there is problem with the blood mechanism it could be a thrombus or an embolus or an volume. So what can the heart pump if there is no blood atherosclerotic plug for example. The thing here is that the or there's blood is not enough because to convey oxygen lumen of the blood vessel is compromised such that there is no and nutrients to the different tissues you need blood as a longer an adequate flow of blood medium. So there should be adequate blood flow otherwise these two features will result in what we call shock GENERAL RESULTS  INADEQUATE TISSUE PERFUSION  CELLULAR HYPOXIA  UN-corrected, a FATAL outcome So the end results of this shock is that there is inadequate tissue perfusion so at the cellular level the cells are deprived of oxygen and because they are deprived of oxygen it depends on the vulnerability of the cell some may be damaged others may die and if is left uncorrected it will cause multiple organ Here is an example of a coronary arteries that cause a damage and might be fatal significant block and it results in the infarction of these heart muscles in the ventricular wall and if you look at under the microscope you can actually see death of these myocytes All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease   PULMONARY EMBOLISM (acute RIGHT heart TYPES OF SHOCK failure or "cor pulmonale")  CARDIOGENIC: (Acute, Chronic Heart Failure) There are many causes of cardiogenic shock:  HYPOVOLEMIC: (Hemorrhage or Leakage)  there is failure of the heart to pump blood; one is of  SEPTIC: ("ENDOTOXIC" shock, #1 killer in ICU) course when the cells of the blood are dying because of  NEUROGENIC: (loss of vascular tone) loss of blood supply that's what happens in myocardial  ANAPHYLACTIC: (IgE mediated systemic infarction. So this is the one of the most common causes vasodilation and increased vascular of cardiogenic shock permeability)  Arrhythmia--there's no adequate cadence of the pumping of the heart because of this arrhythmia; hindi regular ang There are actually several types of shock so one is your cardio contraction ng heart shock and this pertains to the shock caused by the failure of  Cardiac tamponade-- there is an outside force that the heart to pump blood. We only have one heart and if this impinged on the heart that is why the heart cannot heart fails as a pump just like what happened in congestive expand so when it pump it needs space so if there is an heart failure so our peripheral tissues will not receive external force that constrict the pumping action of the adequate blood; if there are blood that can reach the heart, the heart cannot adequately pump blood so that's peripheral tissues it's of low volume no not enough for the what we call cardiac tamponade satisfaction of these peripheral organs. So cardiogenic shock equates to failure of the heart to pump adequate blood So all these conditions lead to failure of the heart to pump adequate blood and that is your cardiogenic shock Hypovolemic shock on the other hand is the result of inadequate blood volume. In our previous segments we know HYPOVOLEMIC shock that water no water about 3 liters of water are found in the  HEMORRHAGE intravascular volume so if there is no adequate amounts of  VOMITING blood how can the blood flow to the different organs if there is  DIARRHEA a very little of blood? so severe hemorrhage especially trauma,.  BURNS Cardiac wound, rupture of aneurysm, aortic dissection so blood escapes from the intravascular space and it can have Hypovolemic shock as I mentioned is inadequate blood volume. serious consequences. So this is what we call hypovolemic So there is a loss of blood that's what happened in massive shock which equates to inadequate blood volume hemorrhage as I mentioned earlier like rupture of aneurysm, trauma, like gunshot injury so the the injury is not repaired as Septic shock is due to massive infection and the underlying soon as so blood will get out of the intravascular compartment pathology here is that there is activation of the inflammatory and it will now cause hypovolemic shock; diarrhea, vomiting, mediators like your cytokines systemically so this will result in and burns actually also cause loss of fluid in the intravascular low blood pressure and low blood pressure will again result to space inadequate flow of blood SEPTIC shock We also have neurogenic shock this is loss of vascular tone  OVERWHELMING INFECTION when all the blood vessels dilate so it will cause blood flow to  "ENDOTOXINS", i.e., LPS (Usually Gm-) the stasis meaning slow down of the blood flow so when there  FUNGAL is slowing down of the blood flow or what we call stasis there  "SUPERANTIGENS", (Superantigens are is inadequate perfusion to the different organs polyclonal T-lymphocyte activators that induce systemic inflammatory cytokine cascades Similarly in anaphylactic shock which is mediated by your IgE similar to those occurring downstream in septic (allergy-hypersensitivity reactions) that is your anaphylactic shock, "toxic shock" antigens by shock and again this cause systemic visodilatation-- slowing Staphyloccoccus aureus are the prime down the flow of blood and there is increased vascular example.) permeability. So blood and water will go out of the intravascular volume so it will further decrease the amount of Septic shock as I mentioned this is caused by overwhelming blood in in the intravascular space. So again it will result in infection; Activation of your mediators of inflammation inadequate perfusion to the peripheral organs systemically so this happens when the microbial agents especially gram-negative bacteria enter the blood. Say CARDIOGENIC shock normally the blood is sterile and when the defense of the host  MYOCARDIAL INFARCTION collapses these microbial agents can penetrate these defenses  VENTRICULAR RUPTURE and it will go through the blood and in the blood it will now  ARRHYTHMIA  CARDIAC TAMPONADE All things work together for good to those who love God- Rom. 8:28 Robbin’s and Cotran Pathologic Basis of Disease activate the mediators of inflammation in a more systemic Shock can be categorized into different stages: manner and this will now cause low blood pressure  the first stage is non-progress progressive so meaning there are compensatory mechanisms that will be SEPTIC shock events* (overwhelming infection) activated to maintain adequate tissue perfusion so for  Peripheral vasodilation example you breathe harder--there's increase in pumping,  Pooling the rate of heart increase-- those are compensatory  Endothelial Activation mechanism just to maintain this adequacy of perfusion of  DIC the different organs. So for example the skin is less vital organs compared to the kidney, to the brain, so most * Think of this as a TOTAL BODY likely they will divert blood from the skin and use that inflammatory response blood to perfuse the more important organs. That is why initially when you have shock, the signs and symptoms Think of septic shock as a total body inflammatory response. includes cold clammy skin because blood is being We probably know that in inflammation, the goal is to localize diverted elsewhere to maintain adequate perfusion in the the injury so what happened if this microbial agents enter the more important organs, bloodstream? so since blood is distributed to the different  Now if these compensatory mechanisms fail it will now parts of the body, inflammation will now be going on enter what we call progressive stage. In this case we now throughout the entire body; that is why septic shock can be have early organ failure; there are actually cells that are considered as a total body inflammatory response and that is quite vulnerable to loss of oxygen. So I repeat that is your: not good because it's very hard to control and there will be  brain cells attendant complications in this type of scenario  your heart cells  and your renal tubular cells ENDOTOXINS So those three cells are very vulnerable to loss of oxygen  Usually Gram-negative bacteria so it will be affected early. So the kidney the brain and the  Degraded bacterial cell wall products heart may be affected if there is a loss of adequate blood  Also called "LPS", because they are Lipo- Poly- supply. At the cellular level, the cells will now shift to an Saccharides anaerobic metabolism since there is lack of oxygen so  Attach to a cell surface antigen known as CD- there is what we call an aerobic mechanism to produce 14 energy and since it is anaerobic there will be build-up of lactic acid. Lactic acid will now cause acidosis and this is This gram-negative bacteria has in its walls called endotoxins manifested in a low ph. That is why when you take your because part of the cell wall are of gram-negative bacteria are ABGs, one of the parameters there is a ph and if there is a your lipopolysaccharides which are actually your endotoxins persistent low ph and because of this loss of adequate and these endotoxins will now elicit an inflammatory response tissue perfusion that can be an early sign that your if you and in this case the response is systemic are in shock that will now be in a progressive state  And this progressive state will now become or will move SEPTIC shock events(linear sequence) on unless corrected into an irreversible stage and  SYSTEMIC VASODILATION (hypotension)→→ irreversible stage no matter how you address the  DECREASE MYCARDIAL CONTRACTILITY→ problem the damage has been done an