Topics A16-21 - Hemodynamic Disorders: Shock, Edema, Thrombosis, DIC, Embolism, Hemorrhages Flashcards Preview

Y Pathology I (Dustin) > Topics A16-21 - Hemodynamic Disorders: Shock, Edema, Thrombosis, DIC, Embolism, Hemorrhages > Flashcards

Flashcards in Topics A16-21 - Hemodynamic Disorders: Shock, Edema, Thrombosis, DIC, Embolism, Hemorrhages Deck (69):
1

Shock definition and some general features

Systemic hypoperfusion, with noted hypoxia, hypotension, and poor removal of waste products. Starts as reversible shock, but eventually becomes irreversible.

It is the final common pathway of many lethal events.

2

What are 3 causes of cardiogenic shock?

1. Pump failure: no proper contractility. Caused by arrhythmias or AMI

2. Diastolic failure: example is cardiac tamponade (bleeding inside pericardial sac -> compresses right side of heart and prevents it from filling in diastole)

3. Outflow failure: for example with pulmonary embolism, right side cannot push past it

3

What are two causes of hypovolemic shock?

1. Bleeding: severe hemorrhage is the classic hypovolemic shock, the basis for most concepts of shock. Physiologists killed so many dogs for this

2. Loss of plasma: for example burning leads to extravasation of plasma. Also severe dehydration.

4

Anaphylactic shock is described in what type of hypersensitive reaction?

Why (very generally) does shock occur here?

HS type I.

Shock occurs because an allergic reaction causes massive histamine release from mast cells and eosinophils, which causes far too much peripheral vasodilation for the body to maintain a healthy blood pressure. This will be in later topics, that's it for here

5

Why does spinal cord injury cause shock? What type of shock is this?

It's called Neurogenic Shock

Occurs because neural tone is necessary to contract peripheral blood vessels. Injury removes this neural tone, and so massive vasodilation occurs.

6

What is the most important shock today? - Why?

Septic shock, because of major risks for hospital-acquired infection and the many immuno-compromised patients (on steroids, chemotherapy, AIDS, etc...)

Robbins says it's the #1 cause of mortality in intensive care units and has a 20-25% mortality rate

7

What pathogenic molecules are normally in the background of septic shock?

PAMPs like LPS (from Gram neg bacteria). It's detected by macrophage PRRs, and macrophages initiate a cytokine storm that causes the major problems of septic shock

8

What are some important molecules that are released in the cytokine storm related to septic shock? (there are 5 that Matolcsy listed)

IL-1
TNF alpha
PDGF
ROS
Prostaglandins

(Others: IL-6, IL-8, NO, PAF, complement activation, goes on and on and on)

9

What are the 3 major consequences of cytokine storm that occur in septic shock?

1. Increased thrombosis, causing DIC (disseminated intravascular coagulation)

2. Increased permeability: edema and hypovolemia

3. Vasodilation: causes hypotension (key feature of shock)

10

What do inflammatory cytokines of the cytokine storm do to the endothelium?

Inflammatory cytokines loosen endothelial tight junctions. The junctions then become leaky, causing fluid to flow out and edema to form.

11

How is metabolism altered during septic shock?

Release of insulin is decreased and peripheral insulin resistance increases, causing the blood glucose level to increase. This provides more fuel for bacteria and helps them proliferate.

Hyperglycemia also decreases neutrophil activity

12

What are 4 major organs effects during multiorgan failure?

1. Bowel becomes leaky with hypoxia, allowing intestinal bacteria to enter circulation

2. Lung: capillary endothelial cells are leaky, causing hyaline membrane disease and ARDS (adult respiratory distress syndrome)

3. Kidney: blood flow is shut off to it, vasoconstricted so blood flows elsewhere. Low urine output, poor filtration, build up of toxic metabolites in kidney, and acute tubular necrosis (ATN)

4. Heart: reduced contractility

13

What is the first of 3 stages of shock? (the Matolcsy classification, it's probably different in the books)

1. Initial progressive stage: most people just call this reversible shock. The shock is under control, compensatory mechanisms like increased sympathetic tone, renin-angiotensin system, etc help keep blood pressure relatively normal.

14

What is the 2nd of 3 stages of shock?

Progressive stage: shock begins to be out of control. Widespread hypoxia occurs. Anaerobic glycolsis causes lactic acidosis, low pH. All generates failure of peripheral circulation

15

What is the final stage in the 3 stages of shock?

Irreversible stage: damage is so severe that even if you were able to restore full hemodynamic function, the person would still die. Enzyme leakage has destroyed too much tissue, renal failure due to tubular necrosis, ischemic bowel has let bacteria into the circulation, etc.

16

What percentage of the body weight is water?
What amount of that is in the intracellular vs extracellular space?

60% BW is water
2/3 intracellular
1/3 extracellular (mostly in interstitial space)

17

What is the difference between transudate and exudate?

Transudate: low-protein fluid (specific gravity <1.012). Occurs with volume or pressure overload or reduced plasma protein content

Exudate: protein-rich fluid (sp. gravity >1.012). Related to inflammation and increased vascular permeability

18

Why does liver failure cause general edema (not just from portal system backup)

What other organ problem may cause the same problem?

The damaged liver has low protein output, especially of albumin, meaning that the blood has reduced colloid osmotic pressure that pulls fluid back from the extravascular space.

Nephrotic syndrome may cause the same problem because the glomerular capillary wall is leaky and loses albumin in the urine

19

Edema can develop from increased hydrostatic pressure in either systemic or local ways. How?

Local: impaired venous return, like a deep vein thrombosis, means hydrostatic pressure builds up backwards in the leg and forces more transudate out of the capillaries

Systemic: increased venous pressure, such in heart failure lowering the return of blood back to the heart. Blood builds up in veins and backwards pressure increases (both pulmonary edema and peripheral edema develop)

20

What are 3 possible pathological causes of pulmonary edema, excluding inflammation? What's the most common one?

1. Reduced osmotic pressure
2. Lymph vessel occlusion
3. Increased venous hydrostatic pressure - this is the most common one, occurs with left-sided heart failure

21

How does pulmonary edema appear in autopsy?

Lungs are heavy due to increased fluid. Consistency is firm yet elastic. Large amounts of bubbly/frothy fluid can be pressed out of a cut surface

22

How does sodium retention relate to edema?

Sodium retention leads to water retention, which increases hydrostatic pressure due to expansion of intravascular volume.

The plasma will also have reduced osmotic pressure.

23

What are 6 mechanisms of edema?

1. Increased intravascular hydrostatic pressure
2. Decreased colloid osmotic pressure in vessels
3. Increased tissue colloid osmotic pressure
4. Decreased lymph drainage
5. Increased capillary permeability
6. Sodium and water retention

24

What are 3 causes of generalized edema?

1. Hypoalbuminemia

2. Right-sided heart failure

3. Rh incompatibility: hydrops in fetus. All organs and interstitium take up fluid

25

What are the 3 stages of nutmeg liver? (Another apparent Matolcsy favorite question)

1. Dilated central veins

2. Congestion -> hypoxia -> yellowish hepatocytes

3. Later: "confluence" occurs where hepatocytes and liver plates are necrotized

26

What is a fancypants patho term for "congestion," like when blood accumulates in a region?

Passive hyperemia

27

What are some generalized forms of congestion / passive hyperemia? (5 are listed, do what you can)

1. Right-sided heart failure
2. Hepatosplenomegaly
3. Congestive gastritis, duodenitis
4. Nutmeg liver
5. Dilated stellate veins

28

What are 3 localized forms of congestion / passive hyperemia?

1. Venous thrombosis

2. Venous compression

3. Torsion, as in testicular

29

What are 5 consequences of chronic congestion?

1. Organ enlargement
2. Induration: tissue becomes firm, also brown due to macrophages eating hemosiderin
3. Atrophy
4. Necrosis
5. Edema

30

What are 6 causes of localized edema?

1. Disturbed venous outflow, e.g. thrombus

2. Disturbed lymph circulation

3. Inflammation

4. Allergy

5. Hypoxia

6. Cerebral space-occupying lesions (perifocal edema)

31

What are 4 general steps of hemostasis?

1. Vascular injury -> endothelin release -> vasoconstriction

2. Primary hemostasis: platelets aggregate

3. Secondary hemostasis: coagulation cascade starts, fibrin polymerizes

4. Antithrombotic mechanisms (tPA, thrombomodulin, etc) regulate the size of the clot

32

What is Virchow's triad?

Determinants for pathological hemostasis

1. Endothelial injury
2. Altered flow
3. Hypercoagulability

33

What are the two types of endothelial injury?

1. Denuding: detachment of endothelial cells. Prediposes thrombosis. Smoking or sepsis may cause.

2. Non-denuding: from hypercholesterolemia etc, produces atherosclerosis

34

What is the consequence of endothelial injury in regards to clotting?

Contact between clotting factors and tissue factor/collagen -> coagulation cascade

Also, endothelial cells normally produce anticoagulant factors like PGI2 and NO; this production is disrupted

35

What two types of abnormal blood flow can lead to thrombosis? What situations do these occur in?

1. Turbulent: occurs where vessels branch, during aneurysms, and in ulcerated atherosclerotic plaques

2. Stasis: occurs in lower vessels with low activity (like deep veins of leg), during atrial dilation/ fibrillation, and hyperviscous syndromes (sickle cell, polycythemia)

36

Why does static blood flow lead to increased risk of blood clots?

Platelets are normally in the center of blood flow, but in static blood the platelets get close to the endothelium, which means more time and exposure to react with thrombogenic substances.

Also, there is less washout of activated clotting factors, and impedes the inflow of clotting inhibitors.

37

What is the difference between primary and secondary hypercoagulability? What are some examples of primary hypercoagulability causes?

Primary hypercoagulability is from genetic mutation causes, secondary is basically any other cause/ acquired

Examples of primary: Factor V Leiden, or prothrombin/antithrombin III mutations

38

What are some examples of things that cause secondary hypercoagulability? (5 listed)

1. Oral contraceptives

2. Disseminated cancers

3. The usual: Age, Smoking, Obesity, Sedentary Lifestyle

4. Heparin-induced thrombocytopenic syndrome (HIT): treatment with unfractionated heparin

5. Antiphospholipid antibody syndrome

39

What are 5 morphological forms of a thrombus?

1. White thrombus / sedimentation thrombus (arterial)

2. Red thrombus / Stagnation thrombus (venous)

3. Composite thrombus

4. Laminated thrombus

5. DIC: disseminated intravascular coagulation

40

What is a composite thrombus?

Head is white, but tail is red. White head is initiated by arterial endothelial injury, but red tail develops behind it with whole blood coagulating

41

What is a laminated thrombus? When does it occur?

Happens during an aneurysm. There is an outpouching of the vessel, making an endothelial origin of white thrombus. Then a white line forms, then red lines, then white again. Called Zahn lines

42

What are 3 ways that a thrombus can be classified based on location?

1. Mural thrombus: in the heart, mostly in the atrium

2. Arterial: whiter than venous due to predominating platelets. Based on atherosclerotic plaque.

3. Venous: mostly red because the vein is precipitated with blood.

43

Which direction to thrombi tend to grow?

Towards the heart, so arterial thrombi grow backwards / retrograde, and venous thrombi grow forwards / anterograde

44

What are thrombi on heart valves called? What causes them?

Vegetations.

May be from bacteria or fungal blood infections

45

What can cause mural thrombi?

1. Atrial fibrillation
2. Mitral stenosis
3. Post-MI aneurysm in ventricles
4. Endocarditis
5. Vegetations

46

How do post-mortem blood clots appear, in contrast to a thrombus?

Post-mortem clots are shiny, soft, gelatinous. Have 2 layers: RBCs on bottom and yellow-white serum on top

Thrombi are usually more homogenous, brownish-red, firmer due to fibrin formation, and surface isn't shiny. They usually attach to the vessel wall.

47

What is the fate of a thrombus? 5 things, essential to know them all

1. Growth/propagation
2. Dissolution/lysis
3. Organization: thrombus embeds in wall, fibroblasts and macropages grow into it, forms a sclerotic plaque
4. Recanalization: becomes partially organized and new blood vessels form through it, restore circulation
5. Embolization

48

What is a pyle thrombosis? (pronounced poo-leh)

Thrombosis in the portal circulation. May be due to liver cirrhosis

49

What are the 2 major consequences of DIC?

What is the mortality?

1. Clots form in small vessels, causing ischemia/necrosis to organs that are highly capillarized (brain, lung, kidney are most affected)

2. All the coagulation factors are getting used up and so the patient starts to bleed, from gums and nose at first.

75-80% mortality

50

What are 4 causes of DIC?

1. Obstetric diseases: mostly from dead fetus causing clotting factors to get into circulation (amniotic fluid embolism)

2. Infection: sepsis. Bacteria over-activate coagulation system

3. Neoplasms: may have procoagulant effects, like acute promyelocytic leukemia involving release of neutrophil granules

4. Trauma: squeezing coagulation into circulation (severe burns, extensive surgery)

51

What stain is used for DIC?

PTAH

52

What are the major locations of thrombi that are at risk for embolizing?

1. Deep veins of leg
2. Auricles: left auricle in A-fib and right auricle in IV drug users.
3. Periprostatic veins
4. Perimetrial veins

53

6 notable types of embolism

1. Pulmonary embolism
2. Systemic embolism
3. Fat embolism
4. Gas embolism
5. Amniotic fluid embolism
6. Tumor cell embolism

54

What are the 4 different classifications of pulmonary embolism? (4th one is tricky)

1. Total: obstruction of pulmonary trunk, rapid death from complete occlusion

2. Subtotal: obstruction of one lung. Survival depends on function of other lung

3. Partial: obstruction goes to small arteries, may cause hemorrhagic infarct

4. Paradox: There is communication btwn atria (foramen ovale). Thrombus moves from left atrium to the right, and into pulmonary circuit

55

What sites are most commonly affected by systemic embolism?

Where do these systemic emboli usually originate from?

-75% go to lower extremities
-10% go to CNS (cause stroke)
-Rest go to intestines, kidneys, spleen, etc.

Systemic emobli usually originate from mural thrombi, such as in A-fib

56

Why does fat embolism occur?

Soft tissue crush injuries or ruptures of bone marrow (or a poorly-placed intramuscular injection) -> fat globules released

Fat doesn't dissolve in blood, so can occlude areas. Free fatty acids are toxic for endothelial cells.

57

What are the two main causes of gas embolism?

1. Decompression sickness: occurs with divers. Under pressure, nitrogen dissolves into the blood, then the person ascends too quickly and the nitrogens bubble -> gas emboli

2. Some surgeries, especially operation of thyroid. Neck veins have negative pressure and may suck air into them. Brain surgery is a similar risk

58

What are 3 forms of decompression sickness?

1. The Bends: just muscle and joint pain

2. The Chokes: more severe, has the pain + dyspnea

3. Caisson disease: chronic form of the bends from repeated diving. Multifocal ischemic necrosis in the heads of the femur, tibia, and humerus

59

How can amniotic fluid emboli occur?

Compression during delivery -> exposure

Amniotic fluid has fetal squamous cells, loaded with tissue thromboplastin, and that gets into maternal circulation causing major thrombogenic response. May cause PE (pulm embolism), CVA (stroke), DIC

60

How do tumor cells cause embolism?

Neoplastic tissue erodes the walls of tissue and it gets into the circulation, has thrombogenic properties

61

What are the 3 major types of bleeding? (note this is only lecture, not in book)

1. Hemorrhagia per rhexin: rupture of vessel

2. Hemorrhagia per arrosionem: vessel is eroded from the outside

3. Hemorrhagia per diapedesis: slow leakage from capillary system where RBCs escape. Related to petechiae and purpura.

62

What are 4 important examples of hemorrhagia per rhexin mentioned in lecture?

1. Apoplexia: small vessel rupture in brain. Charcot-Bouchard (micro)aneurysm is most common cause, normally of lenticulostriate vessels to basal ganglia

2. Epidural hematoma: rupture of middle meningeal artery.

3. Aortic dissection: bleeding into tunica media

4. Rupture of esophageal varices: due to portal hypertension, massive GI bleeding

63

Which population are especially prone to getting epidural hematomas?

What is the normal course of events for this type of bleeding

Alcoholics, as they lose their defending reflexes when they fall

Normal course: person falls and hits head. They have an initial blackout phase of going unconscious, then come back awake with a "lucidum intervallum." Then the bleeding pushes the brain, compressing the cerebellum in the foramen magnum and they lose consciousness again, possibly dying

64

What are 2 examples of hemorrhagia per arrosionem?

1. Chronic gastric ulcers: if erosion reaches vessel, it causes bleeding

2. Tumor arroda (erosion from tumor) - same idea, but the growing tumor disrupts vessel

65

What are the 3 classifications of hemorrhagia per diapedesis?

1. Thrombopathies: related to low platelet count

2. Coagulopathies: low/defective clotting factors

3. Vasculopathies: vessels become more leaky

66

What are 5 examples of thrombopathy-induced hemorrhagia per diapedesis mentioned in lecture?

1. Acute leukemia: no megakaryocytes -> no platelets

2. Aplastic anemia (pretty sure it's the same idea)

3. ITP: Immune thrombocytopenia - antibodies against platelets

4. Hypersplenium / splenomegaly: too many platelets are stuck in spleen

5. Infection: infectious diseases destroy platelets

67

What are 3 examples of coagulopathy-related hemorrhagia per diapedesis?

1. Hepatic cirrhosis: damaged liver cannot produce as many coagulation factors

2. DIC: coagulation factors used up

3. Hemophilia: hereditary disorder of coagulation factors

68

What are 4 examples of vasculopathy-related hemorrhagia per diapedesis?

1. Hypoxia: endothelial cells damaged, RBC's leak. In CO poisoning, get petechiae in the brain

2. Vitamin C insufficiency (Scurvy) - vitC used for collagen formation in vessels

3. Infectious agents: toxins from infection may damage endothelial cells

4. Vasculitis

69

What does slow bleeding cause as a general symptom?

What does massive bleeding in tissues cause as a general symptom?

Slow bleeding -> iron deficient anemia (drains iron stores, cannot replenish RBCs)

Massive bleeding in tissues -> prehepatic jaundice via hemolysis. Hemosiderin accumulates, hyperbilirubinemia and pigment gallstones are also related

Decks in Y Pathology I (Dustin) Class (20):