Literature Review

Question 1

Fresh frozen plasma components

Answer 1

Separated from whole blood and frozen w/in 8 hours
Coagulation factors
Antithrombin
Fibrinogen
Albumi
Alpha-macroglobulins
Stored for up to 1 year when frozen at -20 to -30
evidence it can be refrozen w/in 1 hour of thawing and retain its hemostatic protein activity

Question 2

Frozen plasma definition and components

Answer 2

Plasma that is separated from whole blood but not frozen w/in 8 hours or that has been frozen w/in 8 hours but stored for more than 1 year up to 4 years.

Factors: II, VII, IX, X and albumin

Question 3

Define TRALI and 2 subsets

Answer 3

Transfusion-associated acute lung injury

(1) antibody mediated (transfusion of human leukocyte or neutrophil antibodies and subsequent reaction)
(2) non antibody mediated (accumulation of pro inflammatory mediators during storage of blood products)

Question 4

Describe the classic coagulation pathway

Answer 4

Intrinsic - 12, 11, 9, 8 (localized w/in the blood)
initiated through contact activation of factor XII on negatively charged surfaces

Extrinsic - includes TF and VIIa (localized outside of the blood)

Common - 10, 5, 2, 1 (Factor 10 leads to the activation of prothrombin (II) –> thrombin (IIa) –> fibrinogen (I) –> fibrin (Ia)

Question 5

Describe the cell-based coagulation system

Answer 5

= coagulation occurs in distinct and overlapping phases and requires 2 main cell types: (1) TF-bearing cell (2) platelet.

3 phase: Initiation, amplification, and propagation

Question 6

Describe the initiation phase of the cell-based coagulation system

Answer 6

Injury occurs and blood is exposed to a TF-bearing cell, causing VII to become activated –> results in the production of a small amount of IXa and thrombin that diffuses from the surface of the TF-bearing cell to the platelet.

Question 7

Describe the amplification phase of the cell-based coagulation system.

Answer 7

The small amount of thrombin from the initiation phase activates platelets, releasing vWF and leading to the generation of activated forms of factors (V, VIII, and XI).

Question 8

Describe the propagation phase of the cell-based coagulation system.

Answer 8

Enzymes activated during earlier phases assemble on the procoagulant surface of the activated platelet to form intrinsic tense, which leads to factor Xa generation on the platelet surface and a burst of thrombin generation directly on the platelet that results in fibrin formation.

Question 9

Define INR

Answer 9

International normalized ratio
= Patient PT / mean normal PT

Normal = 0.8 to 1.2, with > 1.5 suggestive of hypocoagulability

Question 10

How is a pro inflammatory state procoagulant?

Answer 10

Inflammation results in pro inflammatory cytokine release, leads to activation of mononuclear cells and endothelial cells.

–> cells produce TF, which initiates coagulation.

+ downregulation of proteins and endothelial cell disruption causes impairment of anticoagulant mechanisms (antithrombin, proteins C, S and TFPI)

Question 11

Mechanism of antithrombin?

Answer 11

Inhibits thrombin and factor Xa

Question 12

Mechanism of activated protein C and S

Answer 12

Degrades cofactors Va and VIIIa

Question 13

Mechanism of TFPI

Answer 13

forms a complex with factors Xa and VIIIa to inhibit coagulation induced by TF

Question 14

List the chemical components of hydroxyethyl starch

Answer 14

Molecular weight
C2/C6 ratio
Raw material
Concentration
MS

Question 15

What makes up hydroxyethyl starch?

Answer 15

Maize and potato starches

Question 16

What are the components of maize and potato in HES?

Answer 16

Maize- 95% amylopectin

Potato - 80% amylopectin and 20% amylose

Question 17

What are the properties of hetastarch compared to vetstarch?

Answer 17

Hetastarch: Concentration 6%, Mw/MS: 600/0.7; maize; 0.9% NaCl; C2:C6 ratio 5:1

Vetstarch: 6%, Mw/MS: 130/0.5; maize, 0.9% NaCl; C2:C6 9:1

Question 18

What is the difference in the 1-3 generations of HES?

Answer 18

1st generation MW > 400
2nd generation: MW 200-400
3rd generation: Mw < 200
*moderateion 3rd generation molecules are characterized by a lower Mw with a narrower range in an attempt to reduce adverse effects and improve pharmacokinetics.

Question 19

Describe the C2/C6 ratio

Answer 19

Natural amylopectin is chemically modified by hydroxyethylation at the glucose subunits C2, C3, or C6 to increase solubility and inhibit degradation by alpha amylase. Average number of hydroxyethyl residues per glucose subunit defines the MS, which higher substitution associated with delayed enzymatic degradation.

Question 20

Define the glycocalyx

Answer 20

Web of membrane bound proteoglycans and glycoproteins that carry a negatively charged side chains, which covers the entire endothelial surface.

Question 21

How does hypervolemia affect the glycocalyx?

Answer 21

Leads to degradation of the glycocalyx. w/ acute hypervoleumia atrial natriuretic peptide is secreted which causes rapid shedding of the glycalyx with subsequent increase in permeability.

Question 22

Is HES anti-inflammatory or pro-inflammatory?

Answer 22

Anti-inflammatory

Decrease in activity of inflammatory cells (decreased activation, migration, adhesion of leukocytes)

Question 23

What molecules effect plasma COP?

Answer 23

Albumin (mainly), globulin, fibrinogen

Question 24

Does hypoalbuminemia cause both peripheral and pulmonary edema?

Answer 24

Causes peripheral rather than pulmonary edema

Question 25

Side effects of HES?

Answer 25

``` Coagulopathies Acute kidney injury Tissue accumulation Anaphylactic reactions Prutitis ```

Question 26

Why is albumin better at generating an improved effect on COP compared to hetastarch?

Answer 26

Albumin is believed to hook into the glycocalyx **it's likely that maintaining an adequate intravascular volume is not really a matter of an adequate COP, rather the health of the glycocalyz**

Question 27

What is the COP paradox?

Answer 27

The ability of albumin (and other colloids) to "seal" the vascular endothelium and reduce extravasation independent of its effect on COP

Question 28

Mechanism of coagulopathy with HES?

Answer 28

(1) dilutional coagulopathy (decreased [ ] of f VIII/vWF complex (2) coating of platelets with HES --> decreased expression and activation of the surface receptor GPIIb IIIa, which binds vWF and fibrinogen and plays a key role in platelet adhesion and aggregation (3) reduced clot firmness due to decreased interaction between activated factor XIII and fibrin

Question 29

How does the C2/C6 ratio affect HES degradation?

Answer 29

High C2/C6 ratio and high MW will delay enzymatic degradation **increase intravascular HES accumulation and result in increased coagulation impairment and plasma viscosity**

Question 30

Define osmotic nephrosis

Answer 30

Histomorphological pattern w/ vacuolization and swelling of the renal proximal tubular epithelial cells (distal tubules and collecting ducts are usually not affected)

Question 31

How is HES degradaded?

Answer 31

alpha amylase degardes | lost in the urine

Question 32

Old/new definitions of sepsis?

Answer 32

Old sepsis = SIRS + bacteria New sepsis = includes tissue hypo perfusion Septic shock = septic patients with circulatory failure despite adequate volume resuscitation

Question 33

What are the recommended choices of vasopressors with septic shock?

Answer 33

Norepinephrine recommended first **can add epinephrine as an additional agent Vasopression can be added to reduce NE dose used or to aid in increasing BP to target; but not to be used as the initial vasopressor **Dopamine is not recommended except in highly selected circumstances**

Question 34

Alpha-adrenergic agonists MOA

Answer 34

Increase vascular tone | May decrease CO and regional blood flow

Question 35

Beta-adrenergic agonists MOA

Answer 35

Maintain CO via positive inotropic and chronotropic effects also have deleterious effects such as increased cellular metabolism and immunosuppression

Question 36

Vasopressin MOA

Answer 36

Synthesized in the hypothalamus and transported to the pituitary gland for storage. Released in response to a decrease in blood pressure, decreased intravascular volume, increased osmolality. Causes constriction of vascular smooth muscle by directly activating the V1 receptors, which leads to an increase in intracellular calcium via the phosphatidylinositol-bisphosphonate cascade.

Question 37

List the subtype vasopressin receptors - location and function

Answer 37

V1 (G protein coupled) - vascular smooth muscle, platelet, liver myometrium, kidney, brain. Causes vasoconstriction, platelet aggregation, glycogenolysis, uterine contraction, efferent arteriolar constriction. V2 (G protein coupled, cAMP) - kidney collecting ducts and vascular endothelium --> insertion of aquoporin-2 channels and release of vWF and factor VIII V3 (G protein-coupled) - located in the brain. Fx,: stress adaption, cognitive function, regulation of social behavior .

Question 38

What is the MOA that vasopressin uses to cause constriction of vascular smooth muscle

Answer 38

Directly activates V1 receptors Leads to an increase in intracellular calcium via the phosphatidylinositol-bisphosphonate cascade.

Question 39

Results of the VASST trial (vasopressin and septic shock trial)

Answer 39

Vasopressin might have decreased mortality when compared to NE in septic shock patients. Low-dose vasopressin plus corticosteroid therapy significantly improved 28-day mortality compared to NE plus corticosteroid therapy.

Question 40

How is D-lactate formed?

Answer 40

Glyoxalase pathway -OR- produced by commensal bacteria in th mammalian gastrointestinal tract and absorbed into circulation

Question 41

Describe glycolysis

Answer 41

Biochemical cascade, by which one 6-carbon glucose molecule is broken down into two 3-carbon molecules of pyruvate, 2 molecules of ATP, and 2 molecules of NADPH Pyruvate is transported into the mitochondrion - undergoes decarboxylation to produce acetyl-CoA (irreversible). Acetyl-CoA then proceeds through the TCA cycle to produce CO2, NADH, and FADH2 When glycolysis, the TCA cycle, and the ETC are combined the oxidation of one molecule of glucose produces about 36 molecules of ATP

Question 42

What effect does lactate have in regards to the Stewart physicochemical approach?

Answer 42

Lactate is a strong anion and has acidifying effects in manner similar to chloride Increase in lactate causes a decrease in SID **and decreasing SID results in a proportionate increase in H+ and therefore acidosis (in accordance w/ the law of electroneutrality)**

Question 43

What does the quantitative approach say about acid-base?

Answer 43

For ever 1 mmol/L increase in lactate, SBE will decrease by 1 unit

Question 44

What is the most reliable place to measure tissue oxygen saturation?

Answer 44

Sartorius

Question 45

What is total hemoglobin index?

Answer 45

Indicator of signal strength and is reported as a unites number between 1 and 99 THI is NOT a measurement of blood hemoglobin - it measures the amount of intravascular hemoglobin, intramuscular myoglobin, melanin, a nd mitochondrial cytochrome c oxidase