Alterations of the Immune/Inflammatory Response Flashcards Preview

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Flashcards in Alterations of the Immune/Inflammatory Response Deck (37)
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1

Inflammation Response

Definition - provides an immediate but nonspecific response to any type of injury to living tissue

 

Characteristics - non-specific means that the inflammation response takes place in the same way no matter what the stimulus is.  Even with a second exposure, this  response occurs in the same way and at the same speed to the same stimulus.

 

Components - mast cells, granulocytes, monocytes/macrophages, endothelium, platelets, fibroblasts, plasma protein systems, mediators

2

Immune Response

Definition - a slower response having the unique charactersitics of memory and specificity

 

Characteristics - memory is the ability to remember previous exposures with specific antigens; the second exposure is not only faster, but stronger.  Specificity is the ability to recognize a particular substance

 

Components -  monocytes/macrophages, lympcytes, mediators

3

Components of the Stress Response

thalamus

hypothalamus

pituitary gland

SNS

adrenal medulla and cortex

mediators

4

Define Infection

a pathological process caused by invasion of the body by pathogenic organisms or potentially pathogenic organisms

5

Define Bacteremia

presence of viable bacteria in the blood; demonstrated by positive blood cultures

6

Systemic Inflammatory Response Syndrome

Definition - Systemic inflammatory response can be triggered by a variety of infectious and non-infectious conditions.  Biochemical features include elevated circulating interleukin 6, procalcitonin, c-reactive protein

Criteria - two or more of the following symptoms: temperature >38.0 or <36.0, heart rate >90 BPM, Respiratory rate >20 breaths per minute, PaCO2 <32mmHg, leukocytosis (WBC count >12,000), leukopenia (WBC <4000), normal WBC count with >10% bands

Triggers - mechanical (surgery, trauma), ischemia (shock, myocardial infarction), chemical (ingestion of toxic substances), microbial (bacterial, viral, fungal & protozoa)

 

7

Define Sepsis

the clinical syndrome defined by the presence of both infection and a systemic inflammatory response

8

Severe Sepsis

Sepsis associated with organ dysfuncton

9

Define Septic Shock

a state of acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes

10

Define Multiple Organ Dysfunction Syndrome

(MODS)

failure of more than one organ in an acutely ill patient such that homeostasis cannot be maintained without intervention

11

Briefly outline the normal response to inflammation

  1. antigen enters the blood stream causing the inflammatory system to release proinflammatory mediators such as TNF, interleukin, chemokines, prostaglandins, and platelet-activating factor to clear antigen and promote recovery of affected tissue
  2. coagulation cascade initiated
  3. maintain this clot, plasminogen activator inhibitor and thrombin activatable fibrinolysis inhibitor are release to suppress fibrinolysis.  this provides the necessary time to destroy the antigen before the clot is lysed
  4. when the antigen is isolated, the proinflammatory mediators attract activated neutrophils, which engulf the antigen
  5. anti-inflammatory markers are released to prevent the proinflammatory response from damaging nromal tissues
  6. the balance of inflammatory and anti-inflammatory mediators restrict the inflammation to the local site of infection

12

How is the inflammatory response altered in sepsis?

  1. the inflammatory response is not localized to the area of infection
  2. in response to infectious pathogens, endothelial cells, epithelial cells, neutrophils, macrophages, and lymphocytes generate and release proinflammatory mediators
  3. cytokines released can also cause widespread vasodilation and activation of coagulation and suppression of fibrinolysis, as well as producing damage to epithelium resulting in leaking capillaries
  4. excess coagulation, exaggerated inflammation, and impaired fibrinolysis associated with the immune response quickly spread beyond the infected area.
  5. these many fibrin clots lead to microvascular hypoperfusion, diminished oxygen delivery, and tissue necrosis.
  6. organ failure follows and the condition progresses to severe sepsis
  7. the procoagulant state results in further endothelial damage, while the vascular damage caused by coagulation leads to the release of more neutrophils and inflammation cytokines
  8. cadiac output may remain normal, or even increase, but at the capillary level, tissue perfusion is impeded and oxygenation is impaire.  Tissue oxygenation is a critical indicator of sepsis that can be detected before organ failures occurs

13

Describe the importance of central venous oxygen saturation and sepsis

  • analyzing blood withdrawn from a CVC placed in the SVC
  • this measurement reflects the oxygen saturation of the blood returning from the upper body
  • severe sepsis results in tissue hypoxia and an imbalance between oxygen delivery and consumption
  • increased oxygen extraction at the tissue level woud reflect a decreased ScvO2
  • the trending of ScvO2 levels provide data on the effectiveness of interventions employed during resuscitation in the setting of severe sepsis

14

How is the patient with severe sepsis identified?

  1. the patient must have an infection or suspected infection
  2. the patient must have 2 or more SIRS criteria
  3. severe sepsis occurs when sepsis is combined with dysfunction of at least 1 organ.  All patients with infections should be closely monitored for the development of severe sepsis.  Important indications of organ dysfunction include altered consciousness, tachypnea, tachycardia, decreased urine output, decreased platelets, and unexplained metabolic acidosis.
  4. when a patient with sepsis fails to respond to fluid rescuscitation and suffers perfusion abnormalities, the patient has developed septic shock
  5. systemic vasodilation, which is demonstrated as low diastolic bloos pressure and systemic vascular resistance leads to severe hypotension.  Afterload of the left ventricle is reduced and the body attempts to maintain perfusion by increasing cardiac output.  Despite this increased cardiac output, body systems remain compromised because a mean arterial pressure of 70mmHg is required to preserve adequate tissue and organ perfusion

15

What are the main components of the management of severe sepsis?

  1. Early goal-directed therapy
    • optimize the balance between oxygen delivery and consumption
    • early initiation of antibiotics for sepsis improves survival, such that every hour of delay results in a worse outcome
    • infusions of colloid or crystalloid, vasoactive agents, and transfusions are used to increase oxygen delivery, with the goal of normalizing SvO2, lactate concentration, base defecit, and pH.
    • the goal is to use plasma volume expansion to resuscitate the microcirculation
    • treatment protocol as per Surviving Sepsis Campaign:
      • central venous pressure 8-12mmHg
      • MAP >65mmHg
      • urine output >0.5cc/kg/hr
      • central venous or mixed venous oxygen saturation >70% or >65% respectively
  2. Fluid Therapy
    • aggressive fluid administration to expand plasma volume, maintain hemodynamic stability, and in turn, optimize perfusiono and oxygen delivery to tissues.
    • there are no firm conclusions with respect to the superiority of colloid (albumin) vs crystalloid (normal saline)
    • pentaspan is not recommended as studies have shown an increased risk of acute kidney injury
    • initial fluid challenges should be at minimum 30cc/kg of crystalloid and should be given as long as hemodynamic improvement is noted
    • septic patients require aggressive, sustained fluid administration due to fluid leakage and maldistribution of blood flow
  3. Vasopressor & Inotropic Therapy
    • goal to increase afterload and improve tissue perfusion
    • norepinephrine is recommended as it increases SAP through stimulation of alpha receptors and subsequently increases vasoconstriction
    • studies snow that patients in septic shock for >24hrs have low endogenous antidiuretic hormone and thus patients may need low dose vasopressin in combination with norepinephrine to increase blood pressure that was unresponsive to adrenergic stimulation alone
  4. Replacement dose corticosteroids
    • if hemodynamic stability is not achieved by fluid and vasopressor/inotropic therapies, hydrocortisone via continuous infusion is recommended
    • appropriate doing of corticosteroid support is thought to enhance vasomotor tone.
    • steroid replacement is required in patients with preexisting adrenal insufficiency
  5. Identify infection and antibiotic regimen
    • pan cultures should be sent to isolate the infectious organism, but broad spectrum antibiotics should be initiated within the first hour of diagnosis of severe sepsis or septic shock.
  6. Supportive measures
    • mechanical ventilation - many patients with sepsis have oxygenation and/or ventilation issues that require mechanical ventilation.  Lung protective measures include lower tidal volumes 6mL/kg and lower peak pressures of <30 cmH2O
    • DVT prophylaxis
    • Stress ulcer prophylaxis - one potential drawback to this therapy is that the increase in stomach pH, bacterial growth, and then aspiration of gastric contents may increase the incidence of patients developing a VAP
    • glucose control via insulin infusion paired with glucose infusion or enteral nutrition

16

Complement cascade as it relates to SIRS and Sepsis Syndrome

  1. Activity
    • produced by macrophages and endothelial cells
    • induction of inflammation
    • mediator between tissue injury and cellular activation such as stimulating neutrophils, chemotaxis, phagocytosis, and aggregation of cells
    • opsonization and lysis of foreign particles and cells
  2. Clinical Response
    • increased vascular permeability, edema, and third spacing
    • decreased SVR, which may be resistant to fluid resuscitation and low dose vasopressor support
    • increased WBCs
    • Increased urinary nitrogen excretion and muscle wasting
    • elevated coagulation lab values

17

Platlet aggregating factor (PAF) as it relates to SIRS and Sepsis Syndrome

  1. Activity
    • produced by platelets, mast cells, basophils, monocytes, macrophages, neutrophils, and damaged endothelium
    • increases adhesion and aggregation of neutrophils and platelets
    • increased vascular permeability
    • negative inotropic effects on the heart
  2. Clinical Response
    • microthrombi, interfering with perfusion
    • third spacing
    • bronchoconstriction, increased pulmonary resistance and wheezes
    • decreased cardiac contractility with decreased cardiac output which is resistant to inotropic therapy

18

Arachidonic acid metabolites as it relates to SIRS and Sepsis Syndrome

  1. Activity
    • produced by cell membrane phospholipids
    • stimulates the release of prostaglandins, thromboxanes, and leukotrienes
  2. Clinical Response
    • pulmonary hypertension which leads to difficulty with oxygenation and ventilation
    • wheezes
    • third spacing and edema
    • decreased with SVR, which may be resistant to fluid resuscitation and low dose vasopressor support

19

Oxygen Free radicals as it relates to SIRS and Sepsis Syndrome

  1. Activity
    • produced by neutrophils, macrophages, oxidative metabolism, and AA metabolism
    • damages cell structure and interferes with cell activities
    • damages endothelium and increases permeability
    • initiates the inflammatory response
  2. Clinical Response
    • third spacing and edema
    • fever
    • microthrombi formation

20

Tumour necrosis factor as it relates to SIRS and Sepsis Syndrome

  1. Activity
    • released by monocytes macrophages
    • stimulates other mediators
    • stimulates immune response
    • endothelial damage
    • induction of fever
    • systemic and local effects
  2. Clinical Response
    • increased vascular permeability, vasodilation, third-spacing
    • hypotension, tachycardia, myocardial depression, tachypnea, hyperglycemia, metabolic acidosis, fever
    • anorexia/wasting

21

Interleukin - 1 as it relates to SIRS and Sepsis Syndrome

  1. Activity
    • released by monocytes, macrophages, and fibroblasts
    • works synergistically with TNF
    • induces inflammation
    • stimulates leukocytes
    • stimulates other mediators
    • procoagulant activity
    • stimulates hematopoesis
    • decreased vascular responsiveness to catecholamines
  2. Clinical Response
    • increased WBC
    • increased urinary nitrogen excretion and muscle wasting
    • elevated coagulation lab values
    • decreased SVR, whichmay be resistant to fluid resuscitation and low dose vasopressor support

22

Interleukin - 6 as it relates to SIRS and Sepsis Syndrome

  1. Activity
    • produced by macrophages, antigen presenting cells, helper T-cells
    • predominantly triggered by TNF, IL - 1 and tissue injury
    • promotion of B cells and differentiation and proliferation of T cells
    • induces inflammation
    • triggers the hypothalamic-pituitary-adrenal axis
  2. Clinical Response
    • decreased SVR, which may be resistant to fluid resuscitation and low dose vasopressor support
    • fever
    • increased neutrophil count

23

Disseminated Intravascular Coagulation

  • an acquired disorder characterized by inappropriate and exaggerated activation of normal blood coagulation, in which there is both thrombosis formation and hemorrhage
  • occurs secondary to a variety of underlying disease processess
  • hypercoagulation, in which fibrin thrombi are formed in the microcirculation of many organs - in an attempt to maintain homeostasis, fibrinolysis occurs in response to excessive clotting and clotting factors are consumed.  This leads to a condition of excessively low clotting factors systemically and hemorrhage
  • can be acute or chronic.
  • chronic DIC is generally a less severe, compensated form of the disorder whereby the liver and bone marrow are not overwhelmed and time allows for replenishment of clotting factors and platelets.  Thrombosis vs bleeding tends to dominate
  • acute DIC is life-threatening with a mortality rate of 50-80%

24

Clinical Conditions Associated with DIC

  • sepsis/severe infection
  • malignancy
  • obstetrics
  • intravascular hemolysis
  • vascular disorders
  • liver disease
  • intravascular prosthetic devices
  • acidosis and alkalosis
  • trauma & burns
  • cardiovascular disease
  • toxins

25

Pathogenesis of DIC

  • disruption of normal coagulation pathways and the processes of fibrinolysis results int he simultaneous occurence of thrombosis and hemorrhage
  • triggers such as severe infection result in the release of TNG and stimulation of the extrinsic coagulation cascade
  • endotoxins also inhibit the activity of protein C- an anticoagulant
  • direct tissue injury, and endothelial cell damage stimulate the intrinsic coagulation pathway
  • once activated, these pathways, in combination with the inflammatory cascade and cytokine release, lead to an increase in circulating procoagulants
  • microthrombi form int he blood vessels and occlude blood flow to tissues and organs
  • the fibrinolytic system attempts to restore balance by breaking down the clots
  • fibrin degredation products (FDP) that result from clot lysis act as anticoagulants
  • these and the depleteion of circulating clotting factors lead to hemorrhage
  • the end result is the perpetuating cycle of excessive clotting and hemorrhage that contributes to pathophysiological imbalance including hypovolemia, hypotension, hypoxia, acidosis, and finally multiple organ dysfunction if the cycle is not interrupted

26

Clinical Manifestations of DIC

  • bleeding
    • petechiae
    • hematuria
    • spontaneous ecchymoses
    • GI hemorrhage
    • hemoptysis
    • bleeding from mucous membranes, venous, and arterial puncture sites or surgical wounds, intracranial hemorrhage
    • multiple organ dysfunction from thrombi in the microcirculation
      • renal
        • proteinuria
        • acute oliguria
        • anuria
      • respiratory
        • acidosis
        • hypoxia
        • dyspnea
      • systemic
        • hypotension
        • coagulation

27

Diagnosis of DIC

  • review of patient history, clinical presentation, and laboratory data
    • DIC is a condition of "consumptive coagulopathy" meaning that clotting factors are being consumed through continuous activation of the clotting cascade.  PTT and INR will be prolonged, platelet counts and fibrinogen levels will be decreased as clots continue to form, and an elevated D-dimer

28

Management of DIC

  1. Prevention
    • prevention of injury and blood loss
    • close monitoring for neurological status (thrombosis or hemorrhage causing alterations in LOC), cardiac function (chest pain, dysrhythmia), pulmonary function (SOB, chest pain, hypoxemia), renal function (oliguria, anuria, increased creatinine), and skin integrity (bruising, hematomas) 
  2. Eliminate Trigger
    • if the trigger cannot be quickly removed, it is difficult to permanently correct the hemostatic defect and further treatment such as volume replacement and strategies to arrest clotting need to be implemented
  3. Stop the Intravascular Clotting Process
    • anticoagulation such as unfractionated heparin used to be used, but it is controversial as it increases the risk of bleeding in DIC
    • antithrombin deficiency may be present in patients with DIC resulting from sepsis, therby negating the effect of heparin
  4. Replace Coagulation Constituents
    • FFP contains the components of coagulation as well as inhibitors
    • cryoprecipitate, containing factors VIII and XIII, fibrinogen, and von Willebrand factor, may also be administered when fibrinogen levels are low
    • Platelet levels may also drop severely necessitating the administration of platelets
  5. Supportive Nursing Care
    • considerations in maintaining circulation and perfusion
    • careful monitoring of vital signs, cardiac output, systemic vascular resistance, oxygen delivery, and oxygen consumption
    • it is critical to avoid any unnecessary bleeding
      • application of pressure dressings to any type of puncture site
      • avoiding any unnecessary punctures
      • careful handling of extremeties and avoiding unnecessary movement

29

Heparin-Associated Thrombocytopenia 

(Type - 1 HIT)

Charactersitics

  • transient, non-immune mediated reaction associated with mild thrombocytopenia
  • occurs in approximately 30% of patients receiving heparin
  • occurs within the first 1 - 4 days of heparin treatment
  • low platelet counts generally return to normal 2-5 days into heparin therapy
  • thrombosis is not associated with HAT
  • discontinuation of heparin is not required

30

Heparin Induced Thrombocytopenia

(Type-2 HIT)

Pathophysiology

  • severe immunologic drug reaction that affects 1 - 3% of patients exposed to standard, unfractionated heparin
  • presents 5 or more days after initiation of heparin but can occur within hours of reexposure if the previous exposure was in the last 3 months
  • causes profound thrombocytopenia and paradoxical thrombosis
  1. platelet factor 4 binds with heparin molecules to form an antigen process
  2. IgG bind to the heparin-PF4 complexes
  3. this interaction results in attachment to platelets and endothelial cells causing platelet activation, aggregation, and the release of thrombin
  4. splenic macrophages attempt to remove the complexes, resulting in thrombocytopenia
  5. once the immune complex is attached to endothelial cell surfaces, tissue factor and other proaggregatory stimuli are released resulting in thrombosis
  6. both arterial and venous thrombosis may develop with type 2 HIT
  7.