NURS 7110 - Module 6 - Immune System

Innate Immune System (1st & 2nd line of defense)

-Response is non-specific
-Exposure leads to immediate maximal response
-Cell-mediated and humoral components
-No immunological memory

Adaptive (Acquired) Immunity (3rd Line of Defense)

- Pathogen & Antigen Specific Response
-Delay between exposure and maximal response
-Cell-mediated and humoral components
-Exposure leads to immunological memory

First Line of Defense

Physical Barrier
1. Skin
2. Mucus, nasal hairs, coughing, sneezing
3. Tear - antibodies and enzymes
4. Gut flora inhibit growth of pathogens.
5. Urine flow, acidic urine, and immunoglobins stopping bacterial growth.

2nd Line of Defense

Inflammatory Response
- Dilation and permeability of vessels to trap harmful molecules.
-Inflammation eliminates the cause, restore metabolism and functions of the organ to a state of dynamic balance.

3rd Line of Defense

Immune Response
- Acquired immunity, more slowly than inflammatory response and can be induced naturally or by vaccination

2 Essential Components of Immune Response

1. Recognition of the presence of foreign substances
2. Taking action to destroy foreign substances.

Systemic Inflammatory Response Syndrome (SIRS)

-Systemic inflammatory response to a variety of severe clinical insults; with two diagnostic findings. These changes should represent an acute change from baseline and be unexplained by other causes.


SIRS, as defined above, as a result of a confirmed infection

Severe Sepsis

- Associated with organ dysfunction, hypoperfusion, or hypotension. Hypoperfusion and perfusion abnormalities may include are not limited to lactic acidosis, oliguria, or an acute alteration in mental status. Hypoperfusion is defined as a SBP <90 mm Hg or

Septic Shock

Sepsis with hypotension despite adequate fluid resuscitation, plus perfusion abnormalities as above. Patients who are on inotropic support may not be hypotensive when these perfusion abnormalities are measured.

Multiple Organ Disfunction Syndrome

Sepsis with hypotension despite adequate fluid resuscitation, plus perfusion abnormalities as above. Patients who are on inotropic support may not be hypotensive when these perfusion abnormalities are measured.

Non-Infectious Causes of SIRS

pancreatitis, multiple trauma, burns, aspiration, ischaemia, and haemorrhagic shock.

Secondary Mediators of Inflammation: Platelet Activating Factor

Promotes cell adhesion and activation, increases platelet activation, is negatively inotropic and enhances microvascular permeability.

Clinical Manifestations of SIRS

- Body temperature, tachycardia, hyperventilation and alteration in WBC count.
- Sweating, fever, chills, and hypotension.
- Dysfunction is defined as an inability of the organ to maintain homeostasis.
- Important manifestations of MODS in SIRS include a

Pathophysiology of Acute Respiratory Distress Syndrome

- Early ARDS occurs in the first week and its characterized by intense lung inflammation with increased epithelial and endothelial permeability , oedema, inflammatory exudates and cells that ifll air spaces, surfactant dysfunction and atelectasis.
- Late

Tachycardia & SIRS

Raise CO and systemic vasodilation

Hypovolemia & SIRS

due to capillary leak, poor oral intake, and fluid loss due to sweating, tachypnoea, vomiting, or bleeding

Hypotension & SIRS

vasodilation, venous pooling, relative hypovolemia and inability to mount a sufficient increase in CO.

Haematological Dysfunction & SIRS

Anaemia and mild coagulation. Severe cases disseminated intravascular coagulation (DIC) and leukopenia can occur. Coagulopathy is caused by activation of extrinsic pathways and deficiencies in some coagulation.


- Ileus frequently occurs especially when there has been a period of hypoperfusion as in septic shock. Sedatives and opioids contribute to impairment of gut function and normal mucosal structure deteriorates.

Brain & SIRS

Mild confusion is common but significant deterioration in conscious levels can occur

Best Indication of End Organ Perfusion and Function?

Urine Output

CXR & Sepsis Diagnostics

Help to differentiate if the lungs are a site of infection. They give information regarding severity of sepsis and MODS in relation to excessive fluid in the lungs. CXRs are also used to assess the cardiac silhouette for enlargement

12 Lead ECG & Sepsis Diagnostics

Gives baseline information regarding the patient's cardiac rhythm. Can also help to differentiate if the heart is a potential site of infection (peri/endocarditis), as well as give information in relation to severity of sepsis and MODS potentially signify

ABG's & Sepsis Diagnostics

Used to evaluate end organ perfusion to the lungs as well as any acid/base imbalance in relation to poor oxygenation/ventilation, as well as metabolic changes r/t compensation or poor perfusion of the tissues. ABGs are required when an accurate PaCO2 leve

VBG's & Sepsis Diagnostics

Assesses the same information as ABG but is less painful, less invasive and, therefor, less risky. There is a good correlation between pH, HCO3, and base excess of VBGs and ABGs. Making VBGs a preferred diagnostic in the emergency department for metabolic

Blood Cultures x2 & Sepsis Diagnostics

Important to determine if the infection has traveled to the blood stream. Will also help to determine appropriate Antibiotics.

WBC w/ Differentials & Sepsis Diagnostics

- Tells us about the potential for infection by calculating the total number of WBCs; will be elevated in the presence of bacterial infection.
- Neutrophils are elevated in the presence of infection in the first 4-8hours. As the infection progresses in se

Hemoglobin & Sepsis Diagnostics

Assesses the oxygen carrying capacity of the blood and may indicate the need for transfusion if severely depleted.

Coagulation Studies (INR/PTT) & Sepsis Diagnostics

Assess for possible coagulopathies in the presence of severe sepsis that can result in Disseminating Intravascular Coagulation (DIC), a life threatening disease process.

Troponin & Sepsis Diagnostics

Assesses potential damage to the heart muscle due to poor perfusion, decreased oxygen supply and increased demand during severe sepsis

Liver Enzymes & Sepsis Diagnostics

Assesses baseline and potential for sepsis-related organ dysfunction/failure. Enzymes, especially bilirubin will be elevated in the context of poor perfusion and liver dysfunction.

Renal Profile (Creatinine, Urea, Bicarb) & Sepsis Diagnostics

Assesses baseline and potential for sepsis related organ dysfunction/failure. Creatinine will be elevated in the context of poor perfusion and Renal dysfunction

Electrolytes & Sepsis Diagnostics

Assesses baseline and any abnormalities that may need to be corrected. For example, Abdul may have elevated potassium if he is experiencing Renal dysfunction. Other electrolytes that may be added are magnesium, calcium and phosphate, as these are essentia

Lactate & Sepsis Diagnostics

Assesses baseline and any abnormalities that may need to be corrected. For example, Abdul may have elevated potassium if he is experiencing Renal dysfunction. Other electrolytes that may be added are magnesium, calcium and phosphate, as these are essentia

Glucose & Sepsis Diagnostics

May be elevated in the context of inflammatory response and sepsis in relation to stress response and the liver dumping glucose into the blood stream for increased metabolic demands

CRP & Sepsis Diagnostics

Indicator of inflammation in the body. May be in response to an infection.

Fluid Therapy & Severe Sepsis

- Crystalloids should be used as initial fluid of choice in resuscitation of severe sepsis and shock.
- Albumin should be initiated in patients who require substantial amounts of crystalloids.
- Aggressive resuscitation with a minimum of 30 mL/kg

Target MAP

>65 mmHg


Raise MAP to target or decrease norepinephrine. Preferred as is a potent vasoconstrictor without the adverse side effects of tachycardia and other dysrhythmias.


Alternate agent with low risk of tachydysrhythmias and absolute of relative bradycardia


Only where norepinephrine is associated with serious dysrhythmias, CO is known to be high and BP persistently low or as salvage therapy when combined inotrope/vasopressor drugs and low-dose vasopressin have failed to achieve MAP target.


1st choice inotrope to improve CO and tissue perfusion


IV hydrocortisone isn't recommended if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability; only suggested if fluid resuscitation and vasopressor therapy are insufficient. Suggested to administer as a continuous


Host response to the presence of microorganisms or tissue invasion by microorganisms


The presence of microbes in circulating blood

Diagnostic Criteria for SIRS

2 or more of the following:
- Temperature >38 or <36
- HR > 90 bpm
- RR >20 breaths/min OR PaCO2 <32 mm Hg
- WBC count > 12,000 mm3, <4000/mm3 OR > 10% immature (band) forms.

Decreased End Organ Perfusion from Sepsis results from

- Micro thrombi impairs capillary blood flow.
-Hypovolemia - d/t vascular permeability
- Unable to increase CO
-Vascular endothelial cells retract from each other increasing vascular permeability
-Decreased vascular tone
-Fever increases metabolism and ox

Function of Kidneys

1. Maintenance of Body Composition: fluid volume, electrolytes, pH
2. Excretion of metabolic & products and foreign substances: Urea*
3. Production & Secretion of Enzymes & Hormones

Acute Kidney Injuries (AKI)

AKI is an abrupt decrease in kidney function meeting this following criteria:
- Increase serum creatinine (SCr) by 0.3 mg/dL or more within 48 hours.
- Increased in SCr to 1.5 times or more the baseline within 7 days prior.
Decreased urine output to less

Difference of AKI and ARF

AKI is temporary. ARF is still used when kidney injury results in the need for RRT

AKI Risk Factors

- Age 65 or older - With aging, the kidney undergoes structural and functional changes. Renal blood flow decreases by 1% per year after age 30. Decreased abi,ity to excrete a sodium load, decreased ability to conserve water, when the patient is dehydrated

AKI Stages

Stage 1 : SCr 1.5-1.9 times baseline or greater than 0.3mg/dL increase with urine output of less than 0.5 mL/kg/h for 6-12 hours.
- Stage 2 - SCr: 2.0 - 2.0 times baseline and urine output of less than 0.5 mL/kg/h for 12 hrs
- Stage 3: SCr: 3 times baseli

Prerenal AKI

Decreased renal perfusion (hypovolemia, decreased CO, and acute hemorrhage, NSAIDs cause arteriolar vasoconstriction)

Intrarenal AKI

Direct injury to the kidneys (blood vessels, glomeruli or tubules-interstitium) Possible causes - ischemia resulting in prolonged decrease in renal perfusion, nephrotoxins, infections, atheroembolic renal disease, and primary renal disease.

Postrenal AKI

Obstruction of urine outflow by tumors, calculi, neurogenic bladder, or prostate gland enlargement. Causes urine to back up into kidney structures, cause increased pressure, decreased GFR, and kidney injury.

Initial Onset Phase of AKI

Between the injury and by identifying hypotensive episodes, nephrotoxic agents and other risks.

Oliguric Phase

Urine ouput decreases <400 mL/day.
- Last 10-14 days +
-Electrolyte imbalances
-Low urine sodium levels

Diuretic Phase

Urine production increases because the nephrons have regained the ability to excrete urea which draws the fluid across the glomerular membrane. urine output: 1-3L/day
-Acid-Base Balance and Electrolytes normalize.

Recovery Phase

Kidneys regain the ability to manage metabolic waste, BUN, and SCr return to baseline. Takes several weeks and up to a year. Kidneys may never fully recover and mild elevations of BUN and creatinine may continue. Some may progress to CKD and need lifelong

Signs / Symptoms of CKD

Chronic normocytic anemia, hypocalcemia, hyperphosphatemia, and grayish cast to skin colour, in addition to elevated BUN and SCr.

Injuries causing AKI

Acute post-streptococcal glomerulonephritis and E. Coli gastrointestinal infection are examples.

Rhabdomyolysis & AKI

Results from large amounts of myoglobin, which is nephrotoxic, being released from injured skeletal muscle (trauma, muscle overexertion, drug overdose or other injuries). Muscle compression, crush injuries, and prolonged immobility can also trigger myoglo

Signs & Symptoms of Fluid Overload

Hypertension, jugular vein distention, acute weight gain, and peripheral edema. S3 may also be auscultated, pulmonary crackles, dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, ascites, and pericardial and or pleural effusions.

Hyperkalemia & AKI

normal excretion of potassium is impaired. Potassium is released from damaged cells. Metabolic acidosis increases potassium levels as hydrogen ions enter the cells and force potassium out of the cells. Can cause cardiac dysrhythmias, peaked T waves, prolo

Metabolic Acidosis & AKI

H+ secretion is impaired. ABG analysis shows low pH and low bicarbonate. Kussmaul respiration is the body's way of attempting to restore the acid-base balance. S/S: flushed skin, headache, tachycardia, N+V, hypotension, bradycardia, and altered LOC.

Diagnostic Studies of AKI

- Urinalysis - checked for specific gravity, osmolality, and sodium levels. Protein or cells in the urine may indicate intrarenal damage (glomerulonephritis, kidney infection of goodpasture syndrome) Hematuria, pyuria, or urinary crystals may indicate a p

Treatment of Hyperkalemia

- IV insulin- drive potassium into the cells. IV dextrose - prevent hypoglycemia.
- Sodium bicarbonate - drive potassium into the cells and help correct metabolic acidosis. Only a temporary fix, because potassium will eventually shift out of the cells aga

Indications fo RRT

- volume overload, compromised oxygenation, metabolic acidosis, cardiac dysrhythmias, pericarditis, pericardial effusion, and impaired neurological status.