Hemodynamic Disorders, Thrombosis And Shock - Chapter 4

Front 1

Define:

• Thrombosis

• Embolism

• Infarction

Back 1

• Thrombosis is an inappropriate blood clot.

• Embolism refers to migrating clots (that may be the result of a thrombosis).

• Infarction is an obstruction of blood supply (that may be caused by an embolism).

Front 2

Edema

• Define "edema".

• What is "ascites"?

• What is "anasarca"?

Back 2

• Edema = Increased fluid in the interstitial tissue spaces.

• Ascites = hydroperitoneum = edema of the peritoneum.

• Anasarca = generalized edema
(Gr. ana, throughout + sarx, flash)

Front 3

Generally speaking, what are the causes of edema?

Back 3

• Increased hydrostatic pressure.

• Decreased colloid osmotic
pressure.

• Lymphatic obstruction.

• Sodium (Na+) retention.

• Increased vascular permeability (due to inflammation).

Front 4

Into what categories can edema be subdivided?

Back 4

• Transudate (protein-poor)
-Due to increased hydrostatic
pressure or decreased colloid
osmotic pressure.

• Exudate (protein-rich)
-Increased vascular permeability
(due to inflammation = inflammatory edema)

Front 5

Edema - Increased hydrostatic pressure.

• What can be the cause of LOCAL increase in hydrostatic pressure?

• What can be the cause of SYSTEMIC increase in hydrostatic pressure?

Back 5

• Impaired venous return
Ex. Deep venous thrombosis.

• CHF of right ventricle
1) The backup of venous blood due to right ventricular insufficiency contributes to edema.
2) The reduced perfusion to the kidneys leads to the activation of the renin-angiotensin-aldosterone system. This mechanism increases the intravascular volume. Normally, this is benificial. However, becasue of the CHF the edema is made worse by this mechanism, which is why drugs to avoid this are a part of CHF-treatment.

Front 6

Edema - Reduced plasma osmotic pressure

• What is the main protein responsible for maintaining this pressure?

• What can cause a decrease of this pressure?

• How does this pathological state react to the renin-angiotensin-aldosterone system?

Back 6

• Albumin

• 1) Albumin is inadequatly synthesized
-Liver cirrhosis
-Malnutrition
2) Albumin is lost from circulation
- Nephrotic syndrome

• The renin-angiotensin-aldosterone system will inevitably be activated because fluid will be lost from the vessels to the interstital spaces. As with CHF, edema is exacerbated by secondary salt and fluid retention.

Front 7

Edema - Lymphatic obstruction

• Local or generalized?

• What may cause such an obstruction?

Back 7

• Local usually

• Inflammation -> Fibrosis
• Neoplasms - Breast cancer
• Post op. - Breast cancer lymph node resection
• Irradiation - Breast cancer.

Front 8

Edema - Sodium (Na+) retention

• Why does Na+ retention cause edema?

• Does it affect hydrostatic pressure or colloid osmotic pressure?

Back 8

• Because an increase in Na+ is always accompanied by an increase in water.

• It affects both

Front 9

Where is edema encountered most often?

Back 9

• Subcutaneous tissue

• Lungs

• Brain

Front 10

• What is "dependent edema"?

• Dependent edema is a prominent feature of what pathology?

Back 10

• Edema of the subcutaneous tissue which involves GRAVITY.
- Involves legs when standing
- Involves sacrum when recumbent

• HF of right ventricle.

Front 11

Pulmonary edema

• Commonly seen as a consequence of what pathology?

Back 11

• HF of left ventricle, but also many other pathologies.

Front 12

How dangerous is edema?

Back 12

That depents on the type of edema:

• Subcutanous edema may impair wound healing and the clearance of infection.

• Pulmonary edema may interfere with ventilatory funtion and cause death.

• Brain edema can cause herniation and consequently death.

Front 13

• What do the terms "hypermia" and "congestion" have in common?

• In what fundamental way do the two differ?

Back 13

• They both refer to a local increase of blood in a particular tissue.

• Hyperemia is an active process
• Congestion is a passive process

Front 14

Hyperemia

• How does it occur?

• Give two examples of when it occurs.

• How does such tissue look?

Back 14

• Due to arteriolar dilation.

1) Inflammation
2) Skeletal m. during exercise

• The affected tissue is redder than normal because of engorgement with oxygenated blood.

Front 15

Congestion

• Why does it occur?

• Give two examples of when it occurs.

• How does such tissue look?

• What condition is related to congestion?

Back 15

• Because of impaired venous outflow.

1) HF (systemic)
2) Venous obstruction (local)

• Blue-red colour (cyanosis) because of the accumulation of deoxygenated hemoglobin.

• Edema

Front 16

Under the microscope, what is the difference between acute pulmonary congestion and chronic pulmonary congestion?

Back 16

• Acute
- Alveolar capillaries engorged in blood
- Some edematic alveolar septa

• Chronic
- Alveolar capillaries engorged in blood
- Thickened and fibrotic septa
- Alveoli may contain hemosideren-laden macrophages (heart-failure cells).

Front 17

When does nutmeg liver occur?

Why does nutmeg liver look like it does?

Back 17

Nutmeg liver occurs in chronic hepatic congestion.

The central veins are are grossly red brown and slightly depressed (because of cell loss).
The surrounding areas are uncongested and normal or sometimes laden with fatty cells due to fatty change.

Front 18

Define

• Hematoma

• Petichiae

• Purpura

• Ecchymoses

• Hemothorax, hemopericardium, hemoperitoneum, hemarthrosis.

Back 18

• Hematoma = Any accumulation of blood

• Petichiae = 1-2 mm hemorrhages in skin or mucous membranes or serosal surfaces

• Purpura = 3-5 mm hemorrhages

• Ecchymoses = bruises = 1-2 cm subcutaneous hematomas

• Larger accumulations of blood in those cavities.

Front 19

What can be the cause of petichiae?

Back 19

• Locally increased intravsular pressure
• Low platelet counts (thrombocytopenia)
• Defective platelet funtion.
• Clotting factor deficiencies.

Front 20

What can be the cause of purpura?

Back 20

• The same as for petichiae
• Trauma
• Vasculitis
• Increased vascular fragility

Front 21

How many percent rapid blood loss can a healthy adult sustain without significant impact?

Back 21

20%

If the blood loss is slow, an even larger percentage is possible.

Front 22

The pathologic form of hemostasis is called?

Back 22

Thrombosis.

Front 23

What components are involved in hemostasis?

Back 23

• The vascular wall

• Platelets

• The coagulation cascade

Front 24

What is the first reaction to vessel injury?
- What causes this?

Back 24

Arteriolar vasoconstriction.
- Reflex neurogenic mechanisms
- Endothelin augments the response

Front 25

• What activates platelets?

• What do the platelets do once they are activated?

Back 25

• Exposed subendothelial extracellular matrix. More specifically TISSUE FACTOR = factor III = thromboplastin.

• Shape change
• Release of secretory granules

Front 26

What is the function of platelet secretory granules?

Back 26

To recruit additional platelets, a process referred to as AGGREGATION.

Front 27

At baseline, what role does the endothelium play in hemostasis?

Back 27

• Antiplatelet

• Anticoagulant

• Fibrinolytic properties.

Front 28

What prevents platelets (dormant and activated) from adhering to endothelium?

Back 28

• Intact endothelium: simply providing a barrier between the platelets and the subendothelial ECM.

• PGI2 (prostacyclin)
• NO
- Both are potent vasodilators and inhibitors of platelet aggregation.

• Adenosine diphosphatase: degrades ADP and further inhibits platelet aggregation.

Front 29

What are the anticoagulant effects of endothelium?

Back 29

• Heparin-like molecules
- They are COFACTORS that allow antithrombin III to inactivate thrombin, factor Xa and several other coagulation factors.

• Thrombomodulin
- 1) Binds to thrombin, converting it from a procoagulant to an anticoagulant capable of activation protein C.
2) Protein C inhibits clotting by proteolytic cleavage of factors Va and VIIIa; it requires protein S, synthesized by endothelial cells, as a cofactor.

Front 30

What are the fibrinolytic properties of endothelium?

Back 30

• Tissue plasminogen activator (t-PA)
- Promoting fibrinolytic activity.

Front 31

What are the prothrombic properties of endothelium?

Back 31

• They secrete vWF which is essential for adherence of platelets (through GpIb) to subendothelial collagen.

• Increased production of tissue factor (factor III/thromboplastin) in response to cytokines (TNF and IL-1) and bacterial endotoxin.

• They secrete plasminogen activator inhibitors (PAI's) which depress fibrinolysis.

Front 32

What are the three reactions that platelets undergo upon activation?

Back 32

• Adhesion and shape change

• Secretion

• Aggregation

In that order

Front 33

What does the primary hemostatic plug consist of?

Back 33

Aggregated platelets.

Front 34

What is the most important protein regulating the coagulation process?

Back 34

Thrombin

Front 35

What is the role of thrombin?

Back 35

It converts fibrinogen into fibrin which polymerizes into an insoluble gel.

Front 36

What is the role of factor XIIIa?

Back 36

It creates crosslinks between fibrin polymers, stabilizing the secondary hemostatic plug.

Front 37

• How can the coagulation cascade be subdivided?

• Which pathway is the most physiologically relevant?

• How are the pathways assesed clinically?

Back 37

• Intrinsic pathway
• Extrinsic pathway - most physiologically relevant.

• Prothrombin time (PT)
-Extrinsic pathway
• Partial thromboplastin time (PPT)
-Intrinsic pathway

Front 38

How does the PT assay work?

What is a normal PT value?

Back 38

Phospholipids (because the components of the coagulation cascade are assembled on phospholipids) and tissue factor (factor III/thromboplastin) is added to a patients citrated plasma.
- The sodium citrate chelates any calcium present and prevents spontaneous clotting.

The clotting reaction is started by adding exogenous calcium, and the time taken to fibrin clot formation is recorded.

11-13 sec.

Front 39

How does the PPT assay work?

What is a normal PPT value?

Back 39

An appropriate surface is added.
Phospholipids are added
- To a patients citrated plasma.

Exoogenous calciuim is added and time to clot formation is added.

28-35 sec

Front 40

What three categories of natural anticoagulants function to control clotting?

Back 40

• Antithrombins
• Protein C and S
• Tissue factor pathway inhibitor (TFPI)

Front 41

What enzyme is responsible for the breakdown of fibrin?

Back 41

Plasmin. It also interferes with the polymerization of fibrin.

Front 42

What prevents plasmin from lysing thrombi indiscriminately?

Back 42

Free plasmin rapidly forms a complex with circulating α2-antiplasmin and is inactivated.

Front 43

What are the three main influences on thrombus formation?

What are are they called?

Back 43

• Endothelial injury
• Statis or turbulence of blood flow
• Blood hypercoagulability

• Virchow's triad

Front 44

In which location is thrombus formation largely a function of endothelial injury.

Back 44

Within cardiac chambers
- The blood is already turbulent
- Hypercoagulability may be negated by the short stay.

Front 45

What forms may endothelial injury take?

Back 45

• Mechanical, in which subendothelial ECM is exposed.

• Disturbances in the dynamic balance of prothrombic and antithrombic activities of endothelium.
-Due to hypertension, turbulent flow over scarred valves or bacterial endotoxins.

Front 46

Into what types can hypercoagulability be subdivided?

Back 46

• Primary (genetic)

• Secondary (aquired)

Front 47

What is the characteristic origin of:

• Arterial thrombi?
• Cardiac thrombi?
• Venous thrombi?

Back 47

• Sites of endothelial injury
• Sites of endothelial injury
• Sites of stasis.

Front 48

What clinical significance do "lines of Zahn" posess?

Back 48

Because they only occur in thrombi in the setting of flowing blood, they can help distinguish a antemortem thrombus from a postmortem thrombus.

Front 49

What cardiac pathological states promote thrombi?

Back 49

• Abnormal myocardial contractions
• Endomyocardial injury

Front 50

Compare the occlusiveness, development of and movement of:
• Arterial thrombi
• Venous thrombi

Back 50

• Arterial
- Frequently occlusive
- Produced by platelet and coag. activation
- Retrograde (toward the heart)

• Venous
- 99% occlusive
- Coagulation cascade.
- Anterograde (toward the heart)

Front 51

What are the possible fates of a thrombus?

Back 51

• Propagation
-The trombus accumulates additional platelets and fibrin, causing further obstruction.

• Embolization
- The thrombus, or fragmentsof it, dislodge.

• Dissolution
- Thrombus is removed by fibrinolytic activity.

• Organization and recanalization.

Front 52

Why is the age of a thrombus clinically important?

Back 52

Because young thrombi are more easily lysed.

Therapeutic administration of fibrinolytic agents (e.g. t-PA) is generally only effective within a few hours of thrombus formation.

Front 53

Venous thrombosis

• What is "phlebothrombisis"?

• Where do they normally occur?

• What is their pathogenesis?

• What are the major risk factors?
- What is their mechanism?

Back 53

• Phlebothrobosis = venous thrombosis (Gr. vein)

• In the superficial or deep veins of the leg.

• Statis
• Variety of hypergoagulable states

• Advanced age
• Bed rest
• Immobilization
- The reduced physical activity reduces the milking activity of muscles.

Front 54

Cardiac and atrial thrombosis

• Name a few causes of such thrombi.

Back 54

• Atherosclerosis
- Because it exposes subendothelial ECM and leads to abnormal blood flow.

• MI ---> Dyskinetic myocardial contraction and damage to the endocardium

• Rheumatic heart disease.

Front 55

• Define the word "emobolus".

• 99% of all emboli represent?

• What is the consequence of an embolism?

Back 55

• An emobolus is a detached intravascular solid, liquid or gas that is carried by the blood to a site distant from it's point of origin.

• Part of a dislodged thrombus (thromboembolism)

• Ischemic necrosis (infarction) of downstream tissue.

Front 56

Pulmonary thromboembolism

• What patients are "high risk" patients?

• What is a "paradoxical embolism"?

• 60-80% of pulmonary emboli are...?

• What happens when 60% or more of the pulmonary circulation is obstructed?

Back 56

• Patients who have already suffered from a pulmonary embolism.

• An embolism that has traveled through an interatrial or interventricular defect, thereby entering the systemic circulation.

• Clinically silent because they are small.

• Sudden death, right ventricular failure (cor pulmonale) or cardiocascular collapse.

Front 57

Systemic thromboembolism

• Most arise from...?

• What are the major sites for arteriolar embolization?

Back 57

• Intracardiac mural thrombi.

• Lower extremities (75%)
• Brain (10%)

Front 58

Fat embolism

• Is normally caused by?

• When do symptoms appear?

Back 58

• Fractures of long bones
• Soft tissue trauma.

• Normally 1-3 days after injury.

Front 59

Air embolism

• What are the causes of air emobilisms?

• How much air is required to produce clinical effects?

Back 59

• Obstetric procedures
• Chest wall injury
• Decompression sickness (nitrogen)

• More than 100 mL

Front 60

Amniotic fluid emobolism

• What does the patient face if surviving the initial crisis?

Back 60

• Pulmonary edema

• DIC - due to release of thrombogenic substances from amniotic fluid.

Front 61

Infarction

• Definition.

• Causes?

• Which organs are most likely to suffer infarcts du to venous thrombosis?
-Why?

Back 61

• An area of ISCHEMIC NECROSIS caused by occlusion of either arterial supply tor the venous drainage in a particular tissue.

• 99% are results of thrombotic or embolic events.

• Testis
• Ovary
- Because they only have a single venous outflow channel.

Front 62

How are infarcts morphologically classified?

Back 62

• On their colour (fedlecting the amount of hemorrhage):
- Red (hemorrhagic)
- White (anemic)

• On the presence or absence of microbial infection:
- Septic
- Bland

Front 63

Where do white infarcts normally occur?

Back 63

With arterial occlusions or solid organs:
• Heart
• Spleen
• Kidney
- The solidity of the tissues limits the amount of hemorrhage that can seep into the area of ischemic necrosis from adjoining capillary beds.

Front 64

What shape does an infarct normally have?

Back 64

Wedge-shaped (<) with the occluded vessel at the apex and the periphery of the organ forming the base.

Front 65

How does time affect the colour of infarcted tissue in:

• Solid organs?

• Spongy organs?

Back 65

• The relatively few extravasated RBC's are lysed. Thus, infarcts resulting from arterial occlusions typically become progressively more pale and sharply defined.

• To many RBC's to become pale. However, the tissue becomes browner and firmer, due to accumulation of hemosiderin.

Front 66

Shock

Regardless of underlying pathology, what does it give rise to?

Back 66

• Systemic hypoperfusion with the end results:
- Hypotension
- Impaired tissue perfusion
- Cellular hypoxia

Front 67

Cardiogenic shock

• Results from?
- Which results from?

Back 67

• HF
- MI
- Ventricular arrhythmias
- Extrinsic compression
- Outflow obstruction

Front 68

Hypovolemic shock

• Results from?
- Which results from?

Back 68

• Loss of blood or plasma volume
- Hemorrhage
- Severe burns

Front 69

Septic shock

• Caused by?
- More specifically?

• Results from?

• How widespread must the microbial infection be to induce septic shock.

Back 69

• Microbial infection
- Mostly gram-negative (endotoxic shock)
- Sometimes gram-positive or fungal

• Host innate immune response to infectious organisms.

• Local extravascular infections may be sufficient. Systemic bacteremia need not be present.

Front 70

What are endotoxins?

Back 70

Bacterial wall lipopolysaccharides (LPS).

Front 71

What is the pathogenesis of septic chock?

Back 71

The endotoxins attach to LPS-binding protein, which in turn binds to monocytes, macrophages and neutrophills via CD14 receptors. ->->-> Cytokines are released -> Vasodilation, enothelial injury, activation of the coagulatory system, diminished myocardial contractility.

Front 72

What are the three stages of shock?

Back 72

1) Nonprogressive stage - Reflex compensatory mechanisms are activated and perfusion of vital organs is maintained.

2) Progressive stage - Tissue hypoperfusion and onset of worsening circulatory and metabolic imbalances.

3) Irreversible stage - Even if the hemodynamic defects are corrected, survival is not possible.

Front 73

What symptoms constitute the clinical triad of septic shock?

Back 73

• Hypotension

• DIC

• Metabolic disturbances

Front 74

Why does shock cause pathology?

Back 74

Because of (prolonged) tissue hypoxia.