Systemic Response to Injury Flashcards
Identifiable source of microbial insult
Infection
SIRS
Two or more of following criteria are met:
- Temperature
≥38°C (100.4°F) or≤36°C (96.8°F) - Heart rate
≥90 beats per minute - Respiratory rate
≥20 breaths per minute
or Paco2 ≤ 32 mmHg or mechanical ventilation
- Abnormal white blood cell count
(≥12,000/μL or ≤4000/μL or ≥10%immature band forms)
Identifiable source of infection + SIRS
Sepsis
Sepsis + organ dysfunction
Severe Sepsis
Sepsis + cardiovascular collapse (requiring vasopressor support)
Septic shock
Traumatic injury results in complex neuroendocrine signaling from the brain.
The two principle neuroendocrine pathways that orchestrate the host response are the
hypothalamic-pituitary-adrenal (HPA) axis,
-which results in the release of glucocorticoid hormones,
and the sympathetic nervous system,
-which results in release of the catecholamines, epinephrine (EPI), and norepinephrine (EPI).
Following injury, corticotrophin-releasing hormone (CRH) is secreted from the
paraventricular nucleus (PVN) of the hypothalamus
ACTH acts on the _____________ to synthesize and secrete glucocorticoids (Fig. 2-3).
Cortisol is the major glucocorticoid in humans and is essential for survival during significant physiologic stress.
zona fasciculate of the adrenal glands
activated in response to stress and tissue hypoxiaby hypoxia-inducible factor 1α (HIF1A)
phenylethanolamine N-methyltransferase (PNMT) transcription
Aldosterone is a mineralocorticoid released by the
zona glomerulosa of the adrenal cortex
It is a mechanism by which ERdistress signals are sent to the nucleus to modulate transcriptionin an attempt to restore homeostasis.
Unfolded protein response (UPR)
a way of disposing of damaged organelles and debris aggregates that are too large to be managed by proteosomal degradation.
“macroautophagy” (autophagy)
An energy-dependent, organized mechanism for clearing senescent or dysfunctional cells, including macrophages, neutrophils, and lymphocytes, without promoting an inflammatory response.
Apoptosis
Apoptosis proceeds primarily through two pathways:
the extrinsic pathway and the intrinsic pathway.
This pathway is activated through the binding of death receptors
Extrinsic pathway
Apoptosis proceeds primarily through two pathways:
the extrinsic pathway and the intrinsic pathway.
This pathway is activated through protein mediators
Intrinsic pathway
refers to the premature uncontrolled death ofcells in living tissue typically caused by accidental exposure to external factors, such as ischemia, inflammation or trauma, which result in extreme cellular stress.
Cellular necrosis
form of regulated cell death that is dependent on the activity of the proinflammatory caspase enzymes associated with the inflammasome
Pyroptosis
a potent inflammatory mediator that is rapidly mobilized inresponse to stressors such as injury and infection.
It is primarily synthesized by immune cells, such as macrophages, dendritic cells, and T lymphocytes
TNFa
Among earliest responders after injury; half-life <20 min; activates TNFreceptors 1 and 2; induces significant shock and catabolism
TNFa
Induces fevers through prostaglandin activity in anterior hypothalamus; promotes β-endorphin release from pituitary;
half-life <6 min
IL-1
IL-1 α and IL-1 β
Promotes lymphocyte proliferation,
immunoglobulin production,
gut barrier integrity; half-life <10 min;
attenuated production after major blood loss leads to immunocompromise; regulates lymphocyte apoptosis
IL-2
Elicited by virtually all immunogenic cells; long half-life; circulating levels proportional to injury severity;
prolongs activated neutrophil survival
IL-6
levels elevated in sepsis, particularly gram-positive infections;
high levels found in cardiac deaths
IL-18
Induces “sickness behavior”
HMGB1
The major precursor of ________ is the omega-6(n-6) polyunsaturated fatty acid (PUFA) linolenic acid
arachidonic acid
Eicosanoids generated from AA include
prostaglandins,thromboxanes, and leukotrienes.
Serotonin is a monoamine neurotransmitter (5-hydroxytryptamine; 5-HT) derived from
tryptophan
are among the first responders to sites ofinfection and injury and as such are potent mediators of acuteinflammation
Neutrophils (PMNs)
main effector cells that sense and respond to “danger signals,”primarily through mechanisms that include phagocytosis of cellular debris, release of inflammatory mediators, and recruitment of additional immune cells to injury sites.
monocytes/macrophages
are the most important antigen-presenting cells (APCs) for initiating T-cell responses against protein antigens
Dendritic cells
was initially known as endothelium-derivedrelaxing factor due to its effect on vascular smooth muscle.
Nitric oxide (NO)
To maintain basal metabolic needs (i.e., at rest and fasting), a normal healthy adult requires approximately
22 to 25 kcal/kg per day
