Inflammation Part 2- Sepsis

Question 1

What type of shock is a septic shock?

Answer 1

distributive shock

Question 2

What is the Inflammatory Response?

Answer 2

inflammation is an attempt by the body to eliminate injurious stimuli & promote healing
- non-specific reaction to stimuli (tissue damage or infective organisms)
-normally helpful but sometimes overreact or underreact (can be seen in sepsis)

Question 3

Sepsis Costs in Canada

Answer 3

much higher than other illnesses
- avg. length of hospital stay is 12 days, vs. 3 days for causes other than sepsis
- patients with sepsis, more commonly admitted to costly intensive care units or ICUs

Age is 1 of the determining factors for incidence of sepsis (very young & very old as most susceptible)

Question 4

Ages that are mostly affected

Answer 4

Neonates: accounts for over 50% of children hospitalized for sepsis
Infants under 2 months: 20%

Largest group hospitalized for sepsis is those over 65 yrs.
- mortality rates rose

Higher in the elderly & immunocompromised

Question 5

What 3 factors contribute to Mortality from Sepsis?

Answer 5

1. Co-morbidities
2. Gender
3. Onset of Sepsis

Question 6

How do co-morbidities contribute to Mortality from sepsis?

Answer 6

mortality rates increase with the number of other physiological derangements

Almost 1/2 of sepsis patients had at least 1 pre-existing condition

Most common comorbidities of sepsis patients in Canada were HIV, cancers, diabetes

Question 7

How does Gender contribute to mortality from sepsis?

Answer 7

Mortality rates were higher in males

31.7 sepsis associated deaths per 100,000 vs. 23.8 deaths per 100,000 in females

Question 8

How does onset of sepsis contribute to mortality from sepsis?

Answer 8

Infections acquired while in the hospital (nosocomial infections) that lead to sepsis, have a higher mortality rate than ion cases where the patient was admitted with sepsis.

Patient whose sepsis occurred after hospital admission had 56& higher odds of dying

Question 9

Why isn’t the Sepsis-3 criteria using SIRS anymore?

Answer 9

No longer uses SIRS (Systemic Inflammatory Response Syndrome)
- described sepsis as an identified/suspected infection, in the presence of 2/more of the following symptoms

• Body temp >38°C or <36°C
• HR >90 beats/min
• RR >20/min (or a PaCO2 of <32 mm Hg)
• WBC count >12,000 mm3 or <4,000 mm3 or >10% bands

> 10% bands indicated body-wide inflammation & may be present instead of Increase or decreased WBC

These markers are still useful for detecting infection but don’t necessarily denote dysregulation of the immune system, or a life-threatening response

SIRS may occur without the presence of infection & some patients admitted to critical care may present with new organ failure & infection but lack the indicators for the sepsis diagnosis

Question 10

What is the new definition of sepsis?

Answer 10

Life-threatening organ dysfunction caused by a dysregulated host response to infection
- the primary cause of death from infection, especially if not recognized & treated promptly

now described by organ dysfunction (assessed by 2 point change in the sepsis-related sequential organ failure score SOFA)
- clients with documented/presumed infection, as organ dysfunction becomes evident, their score would increase

Question 11

What Score do normal healthy individuals get on the SOFA tool?

Answer 11

ZERO

Question 12

What is Septic Shock?

Answer 12

“a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality that with sepsis alone”

In hospital mortality rate for septic shock is greater than 40% & associated with hypotension even with adequate fluid resuscitation

Question 13

Why is the term “sever sepsis” removed from the Sepsis-2 guideline?

Answer 13

because sepsis is a syndrome, it is very heterogenous & affects individuals very differently

Question 14

How to identify Septic Shock in patients?

Answer 14

• Elevated serum lactate levels (>2 mmol/L)
• A need for vasopressor therapy to maintain a minimum mean arterial pressure (MAP) of 65 mmHg (ex: fluid resistant hypotension)

Question 15

What is the qSOFA tool?

Answer 15

Quick SOFA is a new, non-invasive bedside tool that can be used to help identify clients w/ sepsis, if they are experiencing 2 or more of:
1. Systolic BP < 100 mmHg
2. Altered Mentation
3. RR >22/min

if they have 2 out of 3 signs, they are likely to have sepsis

The Glasgow coma scale is used to evaluate mental status a score of < 13= altered mentation
even score < 15 should be evaluated

Question 16

What is PCI?

Answer 16

‘Persistent critical illness’
- those that continue to suffer from organ dysfunction for weeks/months from the initial presentation of sepsis/septic shock (mortality rate of 20-40%)

tends to result in lasting disabilities; cognitive dysfunction, neuropathies, or dysfunctional immune systems

survivors are at high risk for premature death with 5-year mortality rates up to 75%

Question 17

Mitochondrial Dysfunction in Sepsis

Answer 17

previously: sepsis or septic shock was thought to be caused by the lack of perfusion leading to tissue hypoxia & eventual cell death

Now recognized that oxygen may be delivered to the cell, but the cell may be unable to use it efficiently in a condition called= Cytotoxic hypoxia

Lactate may be elevated due to increased glycolysis & inability of the mitochondria to use the lactate
- lactate is also produced under aerobic conditions & is a preferred substrate for the TCA cycle in mitochondria

elevated lactate reduces the ATP produced, leading to energy deficit in cells

As metabolic impairment continues, organ dysfunction occurs, as the # of failing organ systems increases, so does the risk for mortality

Question 18

Hypoxia-induced Metabolic Changes

Answer 18

without oxygen, glycolysis can proceed in the cell’s cytoplasm, but its products, pyruvate & lactate, cannot enter the citric acid cycle within the mitochondrion.

fewer ATP are made by glycolysis, creating an energy deficit, affecting systems such as the sodium-potassium pump

Failure of this pump allows sodium to flow into cell & potassium to leave the cell, upsetting the electrochemical gradient
- gradient is required for action potentials in cells such as neurons & muscle cells so that effects will be evident in the NS & myocardium

These events initiate positive feedback loops that cause greater deterioration of the cell

Ongoing anaerobic metabolism results in an increase in lactate, due to greater production & decrease in use in the mitochondria

The drop in pH is due to protons generated by the hydrolysis of ATP produced by the increased glycolysis

water flows into the cell leading to swelling, cellular membrane disruption, and release of lysosomal contents

Elevations in lactate are now known not to be directly related to acidosis as lactic acid is never produced, only lactate

Glycogen stores are depleted due to reduced nutrient delivery & increased metabolic demands

Protein synthesis is reduced & used of intracellular & plasma proteins for fuel may ensue as nutrients run out

Cellular response to this metabolic stress exacerbates inflammation

Question 19

Interacting Systems Promote Homeostasis

Answer 19

failure of homeostasis is the cause of sepsis, rather than an overwhelming pro-inflammatory response

immune, neural, and neuroendocrine systems cooperate to resolve inflammation by removing threats & repairing damage while returning metabolism & organ function to normal levels

Question 20

How do the Organs promote Homeostasis?

Answer 20

Immune signals that arise in organs travel to the brain along the afferent vagus nerve

Question 21

How do Muscle & Cells promote homeostasis?

Answer 21

Independent of the immune system, sensory nerves surrounding cells detect infection and/or injury & transmit afferent signals to the brain through the dorsal root ganglia & the spinal cord

Question 22

How does the Brain & Efferent pathways promote Homeostasis?

Answer 22

• Sympathetic
• Vagus Nerve

The efferent signals travel through both the sympathetic chain & vagus nerve

Vagal signals act on the adrenal cortex & T-cells in the spleen to release hormones that decrease cytokine expression & release

Sympathetic activation leads to Norepinephrine release, increasing/decreasing cytokine release depending on the type of adrenergic receptor stimulated

Question 23

How does the Neuroendocrine System Promote Homeostasis?

Answer 23

The neuroendocrine system is affected by signals transmitted through the afferent neuronal pathways

cytokines that infiltrate the Blood Brain Barrier as well as cytokines produced by cells of the CNS similarly affect neuroendocrine function

Hormones are subsequently released & affect immune cells such as B-cells, T-cells and macrophages

Question 24

What happens if altered signaling in the 4 pathways that promote homeostasis occurs?

Answer 24

failure to restore homeostasis, which is evident in sepsis, septic shock, and persistent critical illness

Question 25

Immune Cells in Sepsis?

Answer 25

sepsis is pro & anti-inflammatory
- both innate & adaptive immune responses begin to fail, resulting in T-cell exhaustion & the death of many different immune cell types

Metabolic changes associated with sepsis, ultimately result in decreased energy available to individual non-immune cells, drive these cells to prioritize internal homeostasis, causing them to lose their specialization of function & integration within organ systems
- reason for the inability to restore homeostasis

Massive cell death & tissue necrosis is not generally observed on autopsy of septic patients, although loss of immune cells is evident, consistent with the increased apotosis

Question 26

Sepsis & Septic Shock

Answer 26

failure of epithelial & endothelial barriers is a current hypothesis to explain the increased vascular permeability & lack of perfusion observed in clients with sepsis & may also explain why liver enzymes & renal creatinine are able to enter the blood

mechanism by which cytokines & other immune mediators & even immune cells cross the BBB in cases of sepsis

Infection may cause localized organ dysfunction without a systemic response

Question 27

Treatment for Sepsis

Answer 27

Early recognition & treatment are effective ways to deal with sepsis. Better chances of restoring homeostasis & halting the progression to septic shock, organ failure & death

qSOFA tool can help predict risk for mortality & highlight a need for treatment or closer monitoring

Question 28

What is the “Hour-1 Bundle”?

Answer 28

most recent protocol
- measure lactate (remeasure if >2 mmol/L)
- Obtain blood cultures then administer broad spectrum antibiotics
- Administration of fluids (30 mg/kg crystalloids) in the case of hypotension or lactate >4 mmol/L
= saline or Ringer’s lactate (not albumin)
- If hypotension persists, apply vasopressors to maintain MAP >65 mmHg

Question 29

Sepsis Algorithm

Answer 29

Sepsis-3 guideline offers an algorithm for assessing sepsis (qSOFA)

easy way to screen patients at risk for infection at the bedside

Question 30

Consequences of Early Treatment?

Answer 30

The Canadian Institute for Health Information (CIHI) published a report of local success with a bedside rapid response team on the wards that react as soon as the warning signs of sepsis appear

cut down the number of patients who are put into the ICU

experienced fewer cardiac resuscitations in septic patients due to identification & treatment by this team

Question 31

Mechanisms in Sepsis?

Answer 31

now known that immunosuppression can occur simultaneously

predominant new theory of sepsis points to dysfunctional immune & neural systems that result in a failure of homeostasis

research still ongoing to identify not only individual responses that may be prognostic, but also molecular targets for drug development

Hope is to develop specific treatments to augment the supportive measures that are the only course of action at present

Question 32

4 Types of Shock

Answer 32

Cadiogenic
- MI, Arrhythmias, Cardiomyopathy, Severe valve problems, Problems in ventricular flow/filling
- Reduced Stroke Volume (or HR)

Obstructive
- Pulmonary Embolism, Pericardial effusion (tamponade), Tension pneumothorax
- Impaired blood flow

Hypovolemic
- Bleeding (trauma, ulcer), Dehydration (heat shock, diuretics, diarrhea, emesis), burns
- Reduced preload

Distributive
- Sepsis, anaphylaxis, acute brain or spinal cord injury, venoms, overactive thyroid
- low systemic vascular resistance

Question 33

Signs & Symptoms of Shock

Answer 33

Skin:
- Pale
- Clammy
- Cool

Respiratory:
- Rapid breathing
- Shallow respiration

Metabolism:
- Low temperature
- Thirst
- Acidosis
- Low urine output

Neurological:
- Restlessness
- Anxiety
- Lethargy
- Confusion

Cardiovascular:
- Tachycardia
- Thready pulse
- Low cardiac output
- Low BP

Low BP, decrease urine production, poor perfusion leading to acidosis are characteristic of all types of shock

Body temp is decreased in many shocks, but may be increased at the onset of a septic shock (warm & flushed rather than the cool & clammy)

Skin is warm & dry in neurogenic shock, also bradycardia rather than tachycardia

Anaphylactic shock: apprehension, abdominal cramping, coughing, wheezing, appearance of hives

Question 34

What happens in Cardiogenic Shock?

Answer 34

Failure of the heart to pump enough blood to adequately perfuse the tissues, despite ample blood volume= cardiogenic shock is not corrected

often arises as a consequence of MI or severe myocardial ischemia & can be a late-stage result of CAD

The RAAS tries to compensate through fluid retention & vasoconstriction

ADH- is released to increase BV

Adrenal glands release catecholamines to cause vasoconstriction & increase HR (can worsen problem by making heart work harder increasing SVR & preload due to inability to completely empty the ventricle in addition to increased BV)

Pulmonary/ peripheral edema may occur due to fluid overload or mismatched ventricular pumping

myocardial oxygen demands go up due to increased HE & perfusion is impaired due to decreased O2 delivery to myocardium

BP falls due to reduced cardiac output & proper cellular metabolism can’t continue

= dysfunction to heart & other organ systems

Question 35

What happens in Hypovolemic Shock?

Answer 35

caused by any event that reduces fluids such that there is insufficient blood to fill the vascular compartment

may arise as a consequence of hemorrhage, plasma loss due to burns, or massive shift of fluid from the vascular compartment to the extravascular space to replace lost fluids (Ex: excess vomiting or diuresis)

Loss of 10% of blood (volume loss through a blood donation)= not problematic

Amounts above 10%= affect cardiac output & perfusion

Losses of between 35-45% abolish cardiac output & arterial pressure

Blood stored in liver is released into circulatory system & hypothalamus stimulates thirst to increase fluid volume

BP can be maintained by these mechanisms for a short period of time, if vascular volume is not restored, adequate tissue perfusion can’t be maintained & organ dysfunction occurs with possible progression to organ failure.
Similar to compensatory mechanisms of a cardiogenic shock: body retains fluid via the RAAS & release of ADH from pituitary gland & HR is increased

Cardiac contractility is increases, vasoconstriction occurs in extremities to keep vital organs perfused

Question 36

What happens in Neurogenic Shock?

Answer 36

Vasogenic shock, Rarest form of shock & tends to be transitory, a form of distributive shock because there is no loss of fluid, just redistribution that impairs tissue perfusion

occurs when the balance between parasympathetic & sympathetic NS is lost

In addition to spinal cord & brain trauma, can be caused by depressant drugs & anaesthetics, and insufficient delivery of glucose to the brain (may be due to excess insulin)

Widespread vasodilation occurs although there is enough fluid volume, the vascular compartment has expanded, volume is no longer enough

Due to impression of the SNS (one type of shock in which the HR slows instead of escalating, skin remains warm & dry)

Question 37

What happens in Anaphylactic Shock?

Answer 37

results from an overwhelming systemic allergic response & can vary in severity according to the amounts of antigen the patient is exposed to & their sensitivity to the antigen

Vasodilatory substances such as histamine are released in large quantities & increase the capillary permeability & dilates the vessels

can include laryngeal & angioedemas, GI cramps, hives and bronchoconstriction that causes difficulty with breathing

Common antigens: nuts, shellfish, bee stings, drugs such as penicillin

Rapid drop in BP diminishes tissue perfusion & leads to altered mentation

Epinephrine is administered through IM or Iv to cause vascular constriction, reverse airway constriction, curtail mast cell & basophil degranulation, minimize release of histamine & other vasodilatory substances

Due to short half-life of epinephrine, multiple doses may be required

Antihistamines, both short & long-acting may also be required

Individuals with known sensitivities should wear a Medic Alert bracelet & bring a single-dose EpiPen

Question 38

What are the Metabolic Consequences of Shock?

Answer 38

Same for all the shocks, common pathway that leads to organ dysfunction

Switch to anaerobic metabolism results in increase lactate, due to greater production & less utilization

Reduction in efficiency of ATP production & accompanying intracellular consequences of the scarcity in energy

An increase in lactate can occur with metabolic acidosis, but the source of the protons is now known to be separate from the generation of the lactate

hypothesis: protons arise from the hydrolysis that occurs when the ATP produce by glycolysis is utilized

Blood pH drops due to metabolic acidosis which decreases hemoglobin’s affinity for oxygen, aggravating the situation

Delivery of glucose may be decreased by hypoperfusion, but even with adequate blood flow there is evidence of insulin resistance & impaired use of glucose

Uptake of glucose may be reduced due to release of hormones, vasoactive substances & steroid into the blood

Lack of glucose in the cells increase the use of other fuels, lipolysis, glycogenolysis, & gluconeogenesis are all enlisted for energy production

Due to limited supply of glycogen in most cells other than liver & muscles, energy stores are reduced

usage of lipolysis for energy increases the amount of FFA’s & triglycerides in the blood; FFA’s have been found to be cytotoxic, especially to pancreatic beta cells

dysregulations of cellular metabolism can lead to cell death, but gluconeogenesis is the process that can lead to organ failure

use of protein for energy increases amount of urea & toxic ammonia produced, also depletes plasma protein levels allowing movement of more fluid out the vasculature due to lower oncotic pressure

Alanine is generated & once converted to pyruvate can elevate lactate levels

Use of protein from muscles can lead to wasting of skeletal & cardiac fibers & depletion of immunoglobulin proteins can impair immune function= problematic in septic shock

Question 39

What are the treatments for Shock?

Answer 39

successful treatment depends on prompt recognition & rapid intervention

The body’s compensatory mechanisms are usually not enough in reinstating cardiac & vascular balance so pharmacologic treatments must be administered

1. Investigation & discovery of the cause & correction or removal if possible

treatment with fluids such as crystalloids, colloids, or whole blood, if indicated, are used to enhance BV

If vasopressors (to increase BP) or inotropes (to increase myocardial contractility) are needed, they would be administered in the ICU

Patients admitted to the ICU would undergo regular monitoring, usually hourly, to assess effectiveness of these treatments.

Question 40

What is the Pathophysiology of Pancreatitis?

Answer 40

inflammation of the pancreas
- potentially serious condition that may result in hospitalization, organ dysfunction & death

can be acute or chronic, may occur as a mild disease, roughly 20% of patients experience a severe disease course

In addition to its endocrine role releasing the hormones insulin & glucagon into the blood, the primary role of the pancreas is an exocrine gland to deliver digestive enzymes produced in the acinar cells into the duodenum

damage to these cells that is thought to be the cause of pancreatitis

acinar cells generate proteolytic enzymes & amylase, lipases in non-active forms that become activated once they reach the small intestine

because the enzyme trypsin activates the other proteolytic enzymes once cleaved, the acinar cells also secrete a trypsin inhibitor

acinar cell injury leads to activation of trypsin which prematurely activates other enzymes & causes autodigestion of pancreatic tissues

resulting tissue damage provokes inflammation with release of pro-inflammatory cytokines & complement system activation

In more severe cases of pancreatitis the damage is widespread enough to incite systemic inflammation & appearance of SIRS

Shock or other forms of organ dysfunction such as Acute Respiratory Distress syndrome (ARDS) in the lungs or Acute Tubular necrosis (ATN) in the kidneys may occur depending on the severity of the disease process

Large quantity of fluid may migrate to the abdominal cavity & cause a reduction in BV with accompanying hypoperfusion

The lining of the gut becomes dysfunctional due to damage & allows translocation of intestinal bacteria into the blood, resulting in sepsis

Question 41

Most common symptom in pancreatitis?

Answer 41

severe epigastric or mid-abdominal pain, which can radiate to the back & may require narcotics to control

Question 42

Preferred drug for Pancreatitis pain relief?

Answer 42

meperidine hydrochloride or Demerol rather than morphine due to a reduced incidence of spasm in the pancreatic duct sphincter

Question 43

Diagnostic markers for pancreatitis?

Answer 43

Most specific & sensitive: elevated serum lipase level

Serum amylase may be elevated but it is more transient, disappearing upon late presentation

Other inflammatory markers: C-reactive protein (CRP); indicator is also used to evaluate disease severity

Question 44

Common Causes of Pancreatitis?

Answer 44

Most common cause: gallstones, alcohol abuse

Endoscopic Retrograde Cholangiopancreatography (ERCP)- can also irritate the pancreas
- can result in acute pancreatitis, either from mechanical injury of the tissue or due to sensitivity/allergy to the dye

Drug reactions & abdominal trauma can also trigger the condition, as can hypertriglyceridemia

Obesity: can be an increasingly important factor in the prevalence of pancreatitis
- severity increases & # of complications

Question 44

Common Causes of Pancreatitis?

Answer 44

Most common cause: gallstones, alcohol abuse

Endoscopic Retrograde Cholangiopancreatography (ERCP)- can also irritate the pancreas
- can result in acute pancreatitis, either from mechanical injury of the tissue or due to sensitivity/allergy to the dye

Drug reactions & abdominal trauma can also trigger the condition, as can hypertriglyceridemia

Obesity: can be an increasingly important factor in the prevalence of pancreatitis
- severity increases & # of complications

15% are idiopathic cases (unknown cause)

Question 45

What are the treatments for Pancreatitis?

Answer 45

includes pain relief
- in addition to meperidine or morphine, fentanyl is also used for pain relief (especially mild cases since it has less damaging effects on the kidneys than other drugs)

Patients should be NPO to allow pancreas to rest, an NG tube may be used to remove gastric fluids that irritate the condition

Fluids given IV to restore BV & electrolyte balance ( cases of stomach acid removal)

Question 46

What is Somatostatin?

Answer 46

also known as Octreotide
- given IV or subQ as it limits pancreatic secretions, helping the pancreas to rest, aiding healing

Question 47

What scans are used to investigate the cause of Pancreatitis?

Answer 47

-Ultrasound when gallstones are suspected
-CT to scan for the extent of tissue necrosis & accumulation of fluid

Question 48

What is a Cholecystectomy?

Answer 48

Removal of gallstones/ or necrotic tissue removal
- indicated for all patients who have had acute pancreatitis due to gallstones

when possible should be done after recovery, but before discharge from hospital

Question 49

Consequences if gallbladder is not removed if it is the cause of the pancreatitis?

Answer 49

25-30% of cases, pancreatitis will recur within 6-18 weeks if not removed

Gallbladder or bile duct inflammation if not removed, even in mild cases of pancreatitis

Question 50

Treatment of pancreatitis for alcohol-induced cases?

Answer 50

health teaching about the need to discontinue all alcohol use- failure to eliminate alcohol consumption may lead to chronic pancreatitis

Question 51

What supports to give to patients who are NPO due to pancreatitis?

Answer 51

Nutritional support for those who need to be fasted for 7 days or longer

Enteral feeding of patients is preferred to parenteral due to lower risk of infection due to maintenance of the gut barrier

TPN (Total parenteral nutrition)- may be needed if enteral feeding is not well tolerated

Those with mild pancreatitis that resolves in a few days don’t need nutritional supplementation & can resume eating a soft food, low fat diet once pain has subsided

A Cause of pancreatitis in the critically ill receiving parenteral nutrition may be the lipid suspension in the TPN
- may need to be removed & slowly reintroduced as condition resolves