Metabolic/Immunologic background and clinical priorities

Question 1

Stages in critical illness

Answer 1

primary insult -> hypermetabolic inflammatory catabolic state (hyper-metabolism, anorexia, catabolism -> neuroendocrine/cytokine mediated) -> may lead to sepsis/recovery/death

Question 2

Homeostasis in simple fasting

Answer 2

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

Question 3

Homeostasis in severe stress

Answer 3

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

Question 4

Systemic responses that increase in hypermetabolic, inflammatory catabolic state

Answer 4

metabolic rate, body temp, water retention, CO, blood volume, tissue perfusion, free radical production, NO production

Question 5

Skeletal muscle responses that increase in hypermetabolic, inflammatory catabolic state

Answer 5

net proteolysis and amino acid oxidation

Question 6

Liver responses that increase in the hypermetabolic, inflammatory catabolic state

Answer 6

AA oxidation/N excretion, acute phase protein synthesis, gluconeogenesis, Cori cycle

Question 7

Adipose responses that increase in the hypermetabolic, inflammatory, catabolic state

Answer 7

lipolysis/TG turnover

Question 8

Reductions in the hypermetabolic, inflammatory, catabolic state (negative acute phase reactants -> not just a protein deficiency)

Answer 8

production of plasma albumin in the liver, production f plasma IGF-1

Question 9

Systemic inflammatory response syndrome (SIRS)

Answer 9

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%)

Question 10

Compensatory Anti-inflammatory response syndrome (CARS)

Answer 10

term used to describe an immunosuppressed state (unstable state) -> can lead to sepsis

Question 11

Sepsis

Answer 11

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

Question 12

Septic shock

Answer 12

metabolic acidosis and refractory hypotension due to MOF and severe sepsis -> 40-80% mortality risk

Question 13

Neuroendocrine/cytokine response to stress

Answer 13

stress activates hypothalamus directly and the hypothalamus, pituitary and adrenal cortex via local reactions to stress (mediator release, recruitment of cells, wound healing)

Question 14

Hypothalamus

Answer 14

stimulates SNS acting on cardiovascular/pulmonary system, GIT, adrenal medulla, pancreas, kidney and stimulates pituitary and adrenal cortex

Question 15

Pituitary

Answer 15

increased counter regulatory catabolic hormones: adrenalin, glucagon, cortisol and GH

Question 16

Adrenal cortex

Answer 16

reduced anabolic hormones, insulin-resistance: reduced IGF1, T3

Question 17

Neuroendocrine response

Answer 17

increased catabolic hormones and reduced anabolic hormones

Question 18

Immuno-cytokine response

Answer 18

pro-inflammatory mediators: TNF-alpha, IL-1b, IL6, IL8, PGE2, NO, ROS

Question 19

SIRS

Answer 19

influenced by immuno-cytokine response and neuroendocrine response -> systemic catabolic response in muscle and adipose, acute phase response in the liver

Question 20

Critical illness

Answer 20

an unstable state with failed homeostasis, increased energy expenditure and tissue catabolism -> sepsis and death are potential outcomes

Question 21

Intestinal barrier

Answer 21

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)

Question 22

Compromised gut barrier -> endotoxins

Answer 22

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

Question 23

Mesenteric LN

Answer 23

diagnostic of compromised gut barrier

Question 24

Problems due to compromised gut barrier (translocation)

Answer 24

increased intestinal permeability (lack of oral feeding), decreased host immune defense (CARS), increased bacteria due to bacterial overgrowth

Question 25

Nutritional support of immune barrier function

Answer 25

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

Question 26

Bowel rest

Answer 26

delay in EN -> increases the risk of systemic infection by 66% (EN is better than TPN),

Question 27

TPN (intravenous)

Answer 27

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

Question 28

Nutrients

Answer 28

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

Question 29

Intestinal barrier function

Answer 29

crucial to survival and failure can result in sepsis

Question 30

Paraenteral nutrition

Answer 30

may be inadequate may be inadequate and enteral nutrition is needed to support immune barrier function