Path: Hemodynamics 3 & 4

Question 1

_______ is a state of systemic (total body) hypoperfusion, a state of cardiovascular collapse.

Answer 1

Shock

Question 2

Shock is caused by 3 things, commonly. List them, please.

Answer 2

(1) decreased circulating blood volume (hypovolemic)
(2) decreased cardiac output (cardiogenic)
(3) sepsis

Question 3

Decreased circulating blood volume is known as _______ shock and can be due to bleeding or fluid loss from ________, ________ or ____________.

Answer 3

hypovolemic shock; vomiting, diarrhea or extensive burns

Question 4

Decreased cardiac output is called ________ shock and this can be due to myocardial infarction, but it can also be due to cardiac __________ messing up the signaling mechanism for an otherwise adequate pump, ______________ obstructing the output of the right heart or _____________ squeezing the cardiac filling chambers, obstructing filling (“cardiac tamponade”).

Answer 4

cardiogenic shock; arrythmia; pulmonary embolism; hemopericardium

Question 5

Septic shock and its associations such as anaphylaxis, all feature widespread _______, which maldistributes the available blood volume diffusely throughout the body in too many places, returning too little to the heart and lungs to oxygenate and pump it to where it is needed.

Answer 5

vasodilation

Question 6

Is there a threshold blood pressure that can define a state of shock?

Answer 6

No. Blood pressure low enough to cause shock in one pt may be normal for another.

Question 7

Shock is a constellation of signs and symptoms of total body ________.

Answer 7

hypoperfusion

Question 8

One of the earliest symptoms of shock is _______ .

Answer 8

Agitation. A patient with early shock typically becomes irritable, nervous and fidgety, with anxiety. (no, this is not specific to shock)

Question 9

Patients in _________ or _________ shock have a weak, rapid (“thready”) pulse and cool, clammy, sometimes cyanotic skin.

Answer 9

hypovolemic or cardiogenic shock

Question 10

Patients in septic shock have ______, ______ skin.

Answer 10

warm, flushed skin

Question 11

T/F: patients in all forms of shock have decreased urine output.

Answer 11

True

Question 12

Are vital signs safe indicators of shock of any kind? Why or why not?

Answer 12

No. The vital signs are late responders to shock, especially in young people. By the time the heart rate is clearly abnormal (over 100/minute, in an adult) and especially by the time the blood pressure is clearly abnormal (below 90 mm Hg systolic or 40 mm Hg lower than usual), considerable injury to cells and tissue has already occurred.

Question 13

T/F: It is characteristic of young people with shock to compensate better and longer than old people.

Answer 13

True. Young people with shock commonly have deceptively normal vital signs and physiologic functioning until they abruptly reach the limits of their ability to compensate. Then they crash suddenly and profoundly and, frequently, irretrievably.

Question 14

Cardiac tamponade is characterized by a triad of:

Answer 14

shock, distant heart sounds, and jugular venous distension

Question 15

T/F: septic shock is due to vasoConstriction Decreasing the capacitance of the vascular system so much that the amount of blood pooled in the Core leaves too little returning to the Extremities for adequate perfusion of the body as a whole.

Answer 15

False. Due to vasoDilation Increasing the capacitance of the vascular system so much that the amount of blood pooled in the Periphery leaves too little returning to the Heart for adequate perfusion of the body as a whole.

Question 16

_________ shock is a form of vasogenic shock with vasodilation due to spinal cord injury or spinal anesthesia causing acute loss of sympathetic nervous system maintenance of a normal level of vasoconstriction.

Answer 16

Neurogenic shock

Question 17

Trauma patients, especially those with long bone fractures, can have shock that is partly hemorrhagic and partly more like ______ shock due to increased production of proinflammatory cytokines such as:

Answer 17

septic; TNF, IL-1 and IL-6

Question 18

______ shock is the most common of the three major types, at least in surgery and trauma pts.

Answer 18

Hypovolemic

Question 19

How much blood loss (in %) causes signs and symptoms of hypovolemic shock?

Answer 19

25-30% is threshold for shock
25 for older ppl. 30 for younger ppl
loss of 35-45% of a person’s blood causes life-threatening shock. (is treatable)

Question 20

What is the % loss of blood that is commonly regarded as the dividing line between lethal and non-lethal hemorrhage?

Answer 20

50%

Question 21

Are the % cut-offs for blood loss universal?

Answer 21

No. An unhealthy person may die from a blood loss of much less than 50%, especially a person with heart disease.

Question 22

The consensus definition of sepsis is the ______________ due to infection, proven or highly suspected.

Answer 22

systemic inflammatory response syndrome (SIRS)

Question 23

SIRS requires meeting 2 or more of the following criteria:

Answer 23

1- fever (>38C) or hypothermia (90/bpm)
3- tachypnea (RR >20/min)
4- leukocytosis (WBC > 12,000/cu mm) or leukopenia (WBC < 4,000/cu mm) or bandemia (>10% bands)

Question 24

Name and describe the two critical subsets of sepsis.

Answer 24

Severe sepsis- sepsis with acute organ dysfunction

septic shock- sepsis with refractory arterial hypotension

Question 25

Define acute organ dysfunction. You got this.

Answer 25

Malfunction such that a person cannot maintain homeostasis without intervention. Examples include acute alteration in mental status, oliguria (low urine output) or lactic acidosis.

Question 26

Septic shock has a consensus definition of sepsis-induced hypotension with systolic blood pressure less than _________mm Hg or _______mm Hg lower than baseline, refractory to adequate fluid resuscitation, together with acute organ dysfunction.

Answer 26

90 mm Hg or >40 mm Hg

Question 27

Normalization of blood pressure with ___________ suggests that shock is hypovolemic rather than septic.

Answer 27

fluid resuscitation

Question 28

The majority of pts with sepsis have positive or negative blood cultures?

Answer 28

Negative

Question 29

Do the majority of pts with Septic Shock have positive or negative blood cultures?

Answer 29

Positive

Question 30

Babies routinely have resting heart rates well above ___/minute and normal range for their white blood cell counts is up to ______/cu mm.

Answer 30

90bpm; 18,000/cu mm

Question 31

Sepsis causes phospholipase A2 in the cell membranes of platelets, endothelial cells, neutrophils, monocytes and other cells to generate acetyl glycerol ether phosphocholine, better known as _________.

Answer 31

platelet activating factor (PAF)

Question 32

T/F: PAF is between 100 and 1000 times more potent than histamine in inducing vasodilation and increased vascular permeability.

Answer 32

True

Question 33

What is PAF's impact on platelets?

Answer 33

It activates platelets and promotes platelet aggregation.

Question 34

Describe PAF's role in the killing of microbial pathogens as they relate to leukocyte migration and effector function.

Answer 34

PAF promotes leukocyte adhesion to endothelial cells, chemotaxis, degranulation and the oxidative burst that enables microbial killing in leukocytes.

Question 35

Let's play "Do You Remember from Block 1?" Activation of the complement cascade yields C3a and C5a, which (increase/decrease?) vascular permeability and cause (vasodilation/vasoconstriction?) by inducing _______ cells to release histamine.

Answer 35

increase vascular permeability; vasodilation; mast cells

Question 36

Let's play "Do You Remember from Block 1?" If microbial antigens are presented in conjunction with CD3 on the T cell surface and with costimulatory molecules, CD4-positive effector T-cells secrete ____________ that activates phagocytic cells to kill intracellular bacteria, and upregulate their own expression of CD40 ligand, which binds to ______ on the antigen presenting cells, which releases ______ and sustains the expression of costimulatory molecules.

Answer 36

interferon-gamma; CD40; IL-12

Question 37

List the prostaglandins cause vasoDilation.

Answer 37

PGI2, PGD2, PGE1/E2

Question 38

Which prostaglandins cause increased vascular permeability?

Answer 38

PGD2 and PGE2

Question 39

NO is a long or short acting vasoDilator?

Answer 39

Short

Question 40

Describe how NO is used to fight microbial infections.

Answer 40

It is a vasoDilator, increasing blood flow and thus infection fighting cell and molecule arrival to site of infection. It is also produced by activated macrophages and neutrophils, killing microbes by combining with reactive oxygen species.

Question 41

T/F: high amounts of ROS and RNS are not damaging to endothelial cells.

Answer 41

False. Extracellular release of larger amounts of reactive nitrogen species and reactive oxygen species into the bloodstream is damaging to endothelial cells. This damage increases vascular permeability. Increased vascular permeability allows fluid to leak out of the blood into inflamed tissues, decreasing the circulating blood volume.

Question 42

How is clotting factor XII (aka Hageman factor) activated?

Answer 42

Exposure of clotting factor XII (Hageman factor) to activated platelets, basement membrane or collagen activates it.

Question 43

What happens when you activate Hageman factor?

Answer 43

Activated Hageman factor (XIIa), in turn, activates blood clotting, kallikrein* and with that, the kinin cascade**, and via both the clotting and kinin cascades, the fibrinolytic system and the complement cascade. * Plasma kallikrein liberates kinins (bradykinin and kallidin) from the kininogens,[3][4] peptides responsible for the regulation of blood pressure and activation of inflammation. * *kinin system is a poorly understood hormonal system with limited available research. It consists of blood proteins that play a role in inflammation, blood pressure control, coagulation and pain. Its important mediators bradykinin and kallidin are vasodilators and act on many cell types.

Question 44

What role does activated factor X have within the clotting system?

Answer 44

Factor X causes increased vascular permeability and leukocyte emigration from blood vessels. It also converts Prothrombin to Thrombin, right?

Question 45

The fibrinopeptides generated by thrombin increase or decrease vascular permeability?

Answer 45

fibrinopeptides increase vascular permeability

Question 46

Who converts fibrinogen into fibrin?

Answer 46

Thrombin

Question 47

T/F: the fibrinopeptides generated by thrombin are chemotactic for leukocytes.

Answer 47

True

Question 48

T/F: Fibrin cleaves C5 to release C5a, linking clotting and the complement cascade.

Answer 48

False. Thrombin does this.

Question 49

Sepsis causes Increased ______________, which indirectly promotes clotting by inhibiting fibrinolysis.

Answer 49

plasminogen activator inhibitor-1

Question 50

Sepsis results in Decreased ________, _________ and protein ___, all indirectly promoting clotting by decreasing fibrinolysis.

Answer 50

tissue factor pathway inhibitor; thrombomodulin; protein C

Question 51

T/F: sepsis is complicated by DIC in up to 50% of septic pts.

Answer 51

True

Question 52

Just as blood clotting has a counter-regulatory fibrinolytic system, inflammation has a counter-regulatory anti-inflammatory system. Briefly summarize a few of these mechanisms and then explain what happens when the momentum swings too far in the "counter-regulatory" direction.

Answer 52

- Lipoxins inhibit neutrophil adhesion to endothelial cells and chemotaxis. - C1 inhibitor and factor H serve to counter-regulate the pro-inflammatory effects of complement activation. - Activated macrophages secrete IL-10, whose major function is to down-regulate the responses of activated macrophages, calming themselves down. - Soluble tumor necrosis factor receptor (sTNFR) serves to block TNF. Counter-regulatory mechanisms lead to apoptosis of CD4 and CD8 lymphocytes, apoptosis of gastro-intestinal epithelial cells and expression of ligands for inhibitory receptors on lung epithelial cells. These counter-regulatory mechanisms cause immunosuppression. The result is opportunistic infections, reactivation of latent infections and gastro-intestinal hemorrhage.

Question 53

What is compensatory anti-inflammatory response syndrome (CARS)?

Answer 53

The extreme end of the anti-inflammatory spectrum

Question 54

What is mixed antagonistic response syndrome (MARS)?

Answer 54

When pts swing back and forth between a pro-inflamatory and compensatory anti-inflammatory response syndrome.

Question 55

List the 3 targeted therapies against cytokines that block TNF-alpha used to treat autoimmunity.

Answer 55

Infliximab, etanercept, and adalimumab (Humira)

Question 56

Name the targeted therapy against cytokine IL-6 receptors used to treat autoimmunity.

Answer 56

Tocilizumab

Question 57

Explain how superantigens work.

Answer 57

Superantigens are molecules that promote T lymphocyte mitosis in a nonspecific way, bypassing antigen receptor specificity. The toxic shock syndrome toxin-1 (TSST-1), for instance, covers half of the flanking MHC alpha-helices of HLA-DR1, allowing it to bind to any T-cell receptor with a V-beta 2 segment, activating 5-20% of T cell clones instead of the 0.001% activated with normal antigen processing. These numerous clones of activated lymphocytes release mass quantities of cytokines, such as IL-1 and TNF, creating a cytokine storm leading to the systemic inflammatory response syndrome. The result is the toxic shock syndrome.

Question 58

The toxic shock syndrome is due to a nonspecific immunologic over-reaction to a secreted bacterial product, an _______, produced by staph or strep.

Answer 58

exotoxin

Question 59

Severe sepsis or SIRS is defined as sepsis or SIRS with ________________.

Answer 59

acute organ dysfunction

Question 60

The three stages of shock are:

Answer 60

1) non-progressive, with reflex compensatory mechanisms that maintain perfusion of vital organs 2) progressive, with manifestations of decompensating organ function 3) irreversible, with resultant death even if the cause of shock is reversed.

Question 61

Describe the compensatory mechanisms for shock.

Answer 61

Sympathetic nervous system responses (vasoConstriction, increase HR), fluid shifts within the body (move H2O from extravascular compartment into blood, kidneys stop making urine, perfuse only vital organs) and neuroendocrine (increase HR, release epi/norepi, vasopressin-adrenal, renin-renal) stress responses.

Question 62

Why does lactic acidosis occur in progressive stages of shock?

Answer 62

As the body begins shutting down blood supply to non-essential organs, these organs (such as extremity muscles) have to begin anaerobic metabolism. The product of this is lactic acid, which is released into the blood stream and causes lactic acidosis.

Question 63

T/F: septic shock has a point of no return after which nothing will save a person's life. Including returning perfusion to organs.

Answer 63

True

Question 64

What, actually, are "red neurons"?

Answer 64

Neurons begin dying as soon as 4 minutes after losing their blood supply. Starting approximately 12 hours after they die, dead neurons develop condensed cytoplasm rendered hypereosinophilic by the denatured, closely packed cytoplasmic proteins. These are referred to as “red neurons”.

Question 65

The nuclei of dead neurons are hypereosinophilic or hyperbasophilic?

Answer 65

hyperbasophilic

Question 66

The body's compensatory mechanism of shutting off perfusion of the bowel can convert hypovolemic shock into ______ shock.

Answer 66

septic

Question 67

The serosal surface of ischemic bowel takes on a __________ appearance

Answer 67

dusky (dark red)

Question 68

The only way to cure septic shock from ischemic bowel is to __________ it.

Answer 68

surgically resect (remove)

Question 69

T/F: acute kidney injury caused by shock is reversible.

Answer 69

True

Question 70

Describe the gross pathology of acute kidney injury (AKI).

Answer 70

Swollen kidney with pale cortex and congested medulla..

Question 71

Histologically, where is the greatest hit to kidneys in acute kidney injury (AKI)? Describe this microscopic manifestation.

Answer 71

Renal tubules. Manifested by attenuation an loss of proximal tubule epithelial cell brush borders, then epithelial cell swelling and vacuolization, and finally epithelial cell necrosis and sloughing into the tubular lumen. In addition, there may be tubular obstruction by casts of eosinophilic hyaline material, principally Tamm-Horsfall protein, which is a urinary glycoprotein normally secreted by particular portions of the tubules. If shock (or trauma causing shock) has resulted in rhabdomyolysis (skeletal muscle breakdown), there may also be an element of tubular obstruction by myoglobin casts. AKI is also associated with leukocytes in the vasa recta

Question 72

Describe shock's gross and histological effect on the adrenal glands.

Answer 72

Progress from cortical lipid depletion to necrosis and hemorrhage. Resting adrenal cortical cells normally have abundant clear cytoplasm on routine H&E stain, cleared of cholesterol, the precursor for cortisol, aldosterone and the other steroid adrenal hormones. Shock stimulates the adrenal cortical cells to deplete their cholesterol making these stress hormones, which are then secreted into the bloodstream. With progressive shock, adrenal cells die and this adrenal necrosis is frequently accompanied by hemorrhage.

Question 73

What is Waterhouse-Friderichsen syndrome?

Answer 73

Septic shock, especially when due to Neisseria meningitidis infection in children, can lead to massive adrenal hemorrhage and necrosis, obliterating the important adrenal contribution to counteracting shock.

Question 74

Describe the gross pathological impact of shock on the liver.

Answer 74

Nutmeg liver* spanning multiple lobules. *hemorrhagic necrosis spanning multiple lobules alternating with steatotic areas

Question 75

Vulnerability of hepatocytes to ischemia is directly proportional to their proximity to the hepatic __________ veins.

Answer 75

lobular central veins

Question 76

Describe the gross pathological impact of shock on the lungs.

Answer 76

Shock lung is typically enlarged and transformed from an air-filled pink-grey sponge into a firm, solidified, edematous, congested, beefy red organ.

Question 77

Describe the microscopic pathological impact of shock on the lungs.

Answer 77

Microscopically, perhaps the earliest finding is increased numbers of neutrophils in the capillaries in the septa (walls) between alveoli.

Question 78

Shock's effect on the lungs: As soon as half an hour after the lung insult, pulmonary alveolar macrophages produce increased amounts of ___________, which is a strong neutrophil chemotactic and activating agent.

Answer 78

interleukin-8 (IL-8)

Question 79

In relation to shock's effect on the lungs: Release of IL-8 and such proinflammatory cytokines as ______ and _____ activates endothelial cells and leads to sequestration of neutrophils in small pulmonary blood vessels.

Answer 79

TNF and IL-1

Question 80

Shock's impact on the lungs: Neutrophils activated by ____ and ______ upregulate their expression of adhesion molecules that bind to receptors on activated endothelial cells.

Answer 80

IL-8 and TNF

Question 81

Shock's impact on the lungs: Activated neutrophils release a variety of substances, including: (4 things) that damage the alveolar epithelial cells and increase the permeability of the barrier between the airspaces and the bloodstream.

Answer 81

oxidants, proteases, platelet activating factor and leukotrienes

Question 82

Shock's impact on the lungs: With severe injury, breakdown of the ______________ allows whole blood to leak into the alveoli. With less severe (more typical) injury, the alveolar edema fluid condenses into ____________ membranes lining the airspaces.

Answer 82

alveolar-capillary barrier; eosinophilic hyaline

Question 83

Acute lung injury is associated with pulmonary infiltrates on CXR. In severe cases, CXR show complete dense opacification of the lungs referred to as "_______" of the lungs.

Answer 83

"white-out"

Question 84

The ____________ is the severe end of a spectrum with acute lung injury.

Answer 84

acute respiratory distress syndrome (ARDS)

Question 85

What is the consensus definition of ARDS?

Answer 85

The consensus definition of ARDS is an acute condition characterized by bilateral pulmonary infiltrates and severe hypoxemia in the absence of evidence for cardiogenic pulmonary edema.

Question 86

If a person in shock sustains a subendocardial myocardial infarction, but is successfully resuscitated, they tend to have a circumferential infarct involving the anterior left ventricle (name the artery), lateral left ventricle (name the artery) and posterior left ventricle (name the artery).

Answer 86

left anterior descending coronary artery; left circumflex coronary artery; right coronary artery

Question 87

Compare and contrast the contraction band form of necrosis in cardiomyocytes with coagulation necrosis

Answer 87

In contrast to coagulation necrosis of the myocytes, which produces diffusely dense hypereosinophilia of the cytoplasm, contraction band necrosis features transverse bands of dense eosinophilic hypercontracted sarcomeres separated by relatively cleared spaces of cytoplasm.

Question 88

It is thought that what causes the hypercontraction of sarcomeres in contraction band necrosis?

Answer 88

The hypercontraction of the sarcomeres is thought to be due to the influx of calcium brought in by reperfusion, causing the sarcomeres to make one last extreme contraction from which they cannot relax since they have no energy source.