Metabolic/Immunologic background and clinical priorities Flashcards
Stages in critical illness
primary insult -> hypermetabolic inflammatory catabolic state (hyper-metabolism, anorexia, catabolism -> neuroendocrine/cytokine mediated) -> may lead to sepsis/recovery/death
Homeostasis in simple fasting
glycogen and protein are mobilized to provide glucose -> ketogenesis and ketosis increases and glucose needs fall -> metabolic rate slows -> energy needs fall -> protein and energy conservation
Homeostasis in severe stress
glycogen and protein mobilized for glucose and acute phase reactants -> less or no ketogenesis and ketosis (gluconeogenesis from protein remains high) -> metabolic rate rises -> energy needs increase -> accelerated protein and energy depletion
Systemic responses that increase in hypermetabolic, inflammatory catabolic state
metabolic rate, body temp, water retention, CO, blood volume, tissue perfusion, free radical production, NO production
Skeletal muscle responses that increase in hypermetabolic, inflammatory catabolic state
net proteolysis and amino acid oxidation
Liver responses that increase in the hypermetabolic, inflammatory catabolic state
AA oxidation/N excretion, acute phase protein synthesis, gluconeogenesis, Cori cycle
Adipose responses that increase in the hypermetabolic, inflammatory, catabolic state
lipolysis/TG turnover
Reductions in the hypermetabolic, inflammatory, catabolic state (negative acute phase reactants -> not just a protein deficiency)
production of plasma albumin in the liver, production f plasma IGF-1
Systemic inflammatory response syndrome (SIRS)
term used to described hyper-inflammatory state (unstable state) -> 2 or more symptoms: temp > 38 or < 36, heart rate > 90, respiratory rate > 20, leukocytes >12000 or < 4000 -> can lead to sepsis or CARS (mortality risk is 10%)
Compensatory Anti-inflammatory response syndrome (CARS)
term used to describe an immunosuppressed state (unstable state) -> can lead to sepsis
Sepsis
identifiable pathogens in system -> SIRS with assumed or certain infection, mortality risk is 20% -> leads to multi organ failure (20-40% risk of mortality) and eventually shock and death
Septic shock
metabolic acidosis and refractory hypotension due to MOF and severe sepsis -> 40-80% mortality risk
Neuroendocrine/cytokine response to stress
stress activates hypothalamus directly and the hypothalamus, pituitary and adrenal cortex via local reactions to stress (mediator release, recruitment of cells, wound healing)
Hypothalamus
stimulates SNS acting on cardiovascular/pulmonary system, GIT, adrenal medulla, pancreas, kidney and stimulates pituitary and adrenal cortex
Pituitary
increased counter regulatory catabolic hormones: adrenalin, glucagon, cortisol and GH
Adrenal cortex
reduced anabolic hormones, insulin-resistance: reduced IGF1, T3
Neuroendocrine response
increased catabolic hormones and reduced anabolic hormones
Immuno-cytokine response
pro-inflammatory mediators: TNF-alpha, IL-1b, IL6, IL8, PGE2, NO, ROS
SIRS
influenced by immuno-cytokine response and neuroendocrine response -> systemic catabolic response in muscle and adipose, acute phase response in the liver
Critical illness
an unstable state with failed homeostasis, increased energy expenditure and tissue catabolism -> sepsis and death are potential outcomes
Intestinal barrier
mechanical (healthy enterocyte, tight junction, cell turnover, normal motility), bacteriological (aerobic and anaerobic micro-organisms), chemical (gastric acidity, salivary lysozyme, lactoferrin, mucus secretion, bile salts), local immunological (GALT, intra-epithelial lymphocytes, submucosal aggregates, Peyer’s patches, mesenteric LN, secretory IgA), systemic immunological (circulatory lymphocytes, hepatic Kupffer cells)
Compromised gut barrier -> endotoxins
leads to systemic inflammatory response -> release of cytokines (IL-1, IL-6, TNF, PAF, etc), MOF, activation of complement (C3A, C3B, C3C, C3D), decreased splanchnic flow, catabolic hormones (catecholamines), acute phase proteins, release of arachidonic acid metabolites (PGE2, thromboxane, leukotrienes) -> leads to sepsis
Mesenteric LN
diagnostic of compromised gut barrier
Problems due to compromised gut barrier (translocation)
increased intestinal permeability (lack of oral feeding), decreased host immune defense (CARS), increased bacteria due to bacterial overgrowth
Nutritional support of immune barrier function
TPN (total parental nutrition - intravenous), EN (enteral/oral feeding) -> feeding by whatever means in an ICU reduces mortality by 70% -> best is TPN for most of energy but minimal enteral nutrition should be maintained whenever possible -> sufficient EN to stimulate CCK/gut trophic factors and maintain immune function
Bowel rest
delay in EN -> increases the risk of systemic infection by 66% (EN is better than TPN),
TPN (intravenous)
fails to enable proper maintenance of the guy immune system -> fails to provide adequate nutrition to the enterocyte -> PN associated with increase in infectious complications
Nutrients
must provide for systemic metabolic support, GI support and immune system support -> can influence outcome by decreasing the duration and consequences of hypermetabolic phase, decreasing the occurrence of sepsis and improving recovery from sepsis
Intestinal barrier function
crucial to survival and failure can result in sepsis
Paraenteral nutrition
may be inadequate may be inadequate and enteral nutrition is needed to support immune barrier function
