Cardiology - Sepsis Induced Myocardial Dysfunction

Question 1

Which of the following produces interaction between pathogen and the host immune system?

A. Damage Associated Molecular Patterns (DAMPs)
B. Pathogen Associated Molecular Patterns (PAMPs)
C. Interleukins
D. Tumor Necrosis Factors

Answer 1

B. Pathogen Associated Molecular Patterns (PAMPs)

Question 2

What is the host-cell receptor that binds to the PAMPs to produce an immune response?

Answer 2

Toll-like Receptor (TLR)

Question 3

List the assorted inflammatory mediators produced by TLR/PAMP binding?

Answer 3

• Reactive nitrogen/oxygen species
• Superoxide anion
• Nitric oxide

Question 4

What two circulatory dysfunctions are associated with septic shock?

Answer 4

• peripheral vasodilation

- arterial/capillary shunting

Question 5

Explain the “early phase” of septic shock.

Answer 5

This is the “hyper dynamic” or “warm shock” phase. It is characterized by:

• high cardiac output
• low peripheral resistance
• warm extremities

Question 6

Explain the “hypodynamic” or “late phase” of septic shock.

Answer 6

This is the “cold shock” phase. It is characterized by:

• low cardiac output
• poor peripheral perfusion
• cool extremities

Question 7

What is the formula for “cardiac index?”

Answer 7

(LV cardiac output)/Body Surface Area

Question 8

Even with fluid resuscitation and relative hypovolemia, what occurs in the septic patient? Specifically, what occurs with EF and EDV?

Answer 8

There is an increased/normal cardiac index, but they maintain a state of myocardial dysfunction.

These patients present with a low ejection fraction (EF) and a higher end diastolic volume (EDV).
- Recall that EF and EDV are inverse relationships. If less blood is pumped out (low EF), then more blood remains in the heart after diastole (EDF).

Question 9

T/F: Cardiac dysfunction is not associated with increased mortality rates

Answer 9

False. Septic patients with cardiac dysfunction have mortality rates of 70-90% compared to 20% mortality of patients w/o cardiac dysfunction.

Question 10

What specific portion of vascular tissue plays a crucial role in myocardial dysfunction associated with sepsis? Why?

A. Tunica intima (Endothelium)
B. Tunica media
C. Tunica adventitia

Answer 10

A. Endothelium

The endothelium, or tunica intima, plays a pivotal role in the control of peripheral vascular resistance via vasoactive molecules. Specifically, nitric oxide (NO) derived from the endothelium is decreased in sepsis.

This failure to release NO causes vasospasm and increased PVR. These increase the workload on the heart.

Look this up, bcause the explanation doesn’t make sense on p. 3

Question 11

Early sepsis may be considered a form of _____ shock.

A. Hypovolemic
B. Distributive
C. Cardiogenic
D. Obstructive

Answer 11

B. Distributive

Circulatory abnormalities (including vasodilation) occur in early sepsis.

Question 12

T/F: Current research indicates that global ischemia associated with sepsis is the cause of myocardial dysfunction in septic patients.

Answer 12

False

Question 13

Explain what three changes to cardiac microcirculation have been found in dogs with endotoxemia.

Answer 13

• heterogeneous microvascular blood flow
• swollen endothelial cells
• intravascular fibrin distribution

Question 14

______ and ______ may contribute to the pathophysiology of septic cardiomyopathy.

A. Inadequate blood flow; neutrophil deposition
B. Endothelial damage; coagulation induction
C. Adequate oxygen levels; fibrin deposition

Answer 14

B. Endothelial damage; coagulation induction

Question 15

The myocardium may be attenuated at the myocyte by what two mechanisms?

Answer 15

• down-regulation of beta-receptors

- cardiomyocyte damage due to toxins, complement, DAMPs, etc.

Question 16

Myocardial depressant factor is a small peptide responsible for cardiac depression in sepsis. By what mechanism does this occur?

A. Direct damage to cardiomyocyte walls
B. Decrease in myocyte shortening
C. Down regulation of beta-adrenergic receptors

Answer 16

B. Decrease in myocyte shortening

Question 17

TNF-alpha and IL-1beta cause the release of _____, depressing cardiomyocytes in sepsis further.

A. MDF
B. IL-12
C. Nitric oxide

Answer 17

C. Nitric oxide

Question 18

Sepsis induces action of what specific enzyme in the myocardium?

A. NO synthase
B. ATP synthase

Answer 18

A. NO synthase

Question 19

NO synthase induced in the myocardium leads to increase in sarcoplasmic reticulum _______.

A. H+
B. Ca2+
C. Cl-
D. K+

Answer 19

B. Ca2+

As Ca2+ is sequesterd in the SR, there is no Ca2+ release, which reduces myocyte contractility.

Question 20

What cellular organelle is plentiful in myocardial tissue?

A. Mitochondria
B. ATPase
C. Na/KATPase

Answer 20

A. Mitochondria

Question 21

What specific ETC complexes are inhibited in sepsis?

Answer 21

Complexes I + II

Mitochindria fall victim to “mitochondrial edema,” The resulting myocardial dysfunction MAY represent an adaptive mechanism. In other words, low ATP may lead to mitochondrial dysfunction. The myocardium “realizes” there isn’t enough ATP to power normal operations, so it reduces its workload.

Question 22

During sepsis-induced myocardial dysfunction, the mitoch. release what compounds into circulation?

Answer 22

DAMPs
mtROS
mtDNA
cytochrome C

Question 23

This functions to promote phagocytosis after binding antigen.

A. CD84
B. TLR2
C. TLR4
D. eNOS

Answer 23

B. TLR2

Question 24

This functions to promote NF-kB and cytokines production after binding antigen.

A. CD84
B. TLR2
C. TLR4
D. eNOS

Answer 24

C. TLR4

Question 25

Which molecule binds TLR2 and TLR4 to stop ATP production in cardiomyocytes?

Answer 25

Exogenous histones

Question 26

Circulating histones in SIMD corresponds to elevation of what biomarker?

Answer 26

Cardiac troponin (cTnT)

Question 27

Outline the pathology of decreased cardiac contractility in sepsis.

Answer 27

Believed that HMGB1 produces ROS.
This is caused by interaction between HMGB1 and the TLR4.
Furthermore, the Ryanodine-R located on the sarcoplasmic reticulum of cardiomyocytes becomes phosphorylated. Upon Ry-R-Pi binding, SERCA activity decreases.

Calcium leaks into cytosol where it is cytotoxic

Question 28

What is the primary concern/potential problem with EGDT in EMS management of sepsis?

A. Fluid overload/pulmonary edema
B. Hypertension
C. Hyponatremia

Answer 28

A. Fluid overload/pulmonary edema

Question 29

Why is maintenance of adequate perfusion pressure so important in shock?

Answer 29

Normalizing blood pressure allows for more adequate delivery of oxygen to tissue, which prevents further release of DAMPS associated with sepsis/anoxia in tissues.