Download MBBS (Bachelor of Medicine, Bachelor of Surgery) General Surgery PPT 5 Homeostasis Lecture Notes
HOMEOSTASIS
Concepts of Homeostasis
? Claude Bernard:
? Stability of the "milieu int?rieur" is the primary condition for freedom and independence of
existence.
? i.e. body systems act to maintain internal constancy.
? Walter Cannon:
? Term "Homeostasis".
? Coordinated physiological process which maintains most of the steady states of the organism.
? i.e. complex homeostatic responses involving the brain, nerves, heart, lungs, kidneys and spleen
work to maintain body constancy.
? Responses to injury are beneficial to the host and al ow healing/survival.
Concepts of Homeostasis......
? Classical homeostatic control system:
? Signal detector
? Processor
? Effector
? Negative feedback loop
? Open loop system:
? Also referred to as non-feedback system
? Type of continuous control system in which the output has no influence or effect on the control
action of the input signal.
? Only with medical/surgical resolution of the primary abnormality results in classical homeostasis.
Concepts of Homeostasis......
? Elective surgical practice:
? Reduce the need for a homeostatic response by minimizing the primary insult
? e.g. minimal access surgery and `stress-free' perioperative care.
? Emergency surgery:
? Presence of tissue trauma/ sepsis/ hypovolaemia often compounds the primary problem.
? It requires:
? To augment artificial y homeostatic responses (e.g. resuscitation)
? And to close the `open' loop by intervening to resolve the primary insult (e.g. surgical treatment of major abdominal sepsis)
? And provide organ support (critical care)
? While the patient comes back to a situation in which homeostasis can achieve a return to normality.
Graded Nature of the Injury Response
? Response to injury:
? More severe the injury- Greater the response.
? Applies to Physiological/ Metabolic/ Immunological changes.
? Following elective surgery of intermediate severity-
? Changes may be a transient and modest.
? Mild rise in temp./ heart rate/ respiratory rate/ energy expenditure and white cel count.
? Following major trauma/sepsis-
? Changes are accentuated.
? Resulting in SIRS/ hyper metabolism/ marked catabolism/ shock and even multiple organ dysfunction (MODS).
? Genetic variability plays a key role in determining the intensity of the inflammatory response.
Graded Nature of the Injury Response....
Response to injury:
Hypermetabolism and increased nitrogen excretion are closely related to the magnitude of the initial injury and show a gradedresponse.
Graded Nature of the Injury Response....
? Immunological sequelae of major injury:
? Evolve from a Pro-inflammatory State
? Driven primarily by the innate immune system (macrophages, neutrophils, dendritic cel s).
? Finally- Compensatory Anti-Inflammatory Response Syndrome (CARS)
? Characterized by suppressed immunity- diminished resistance to infection.
? Patients who develop infective complications-
? CARS leads to ongoing systemic inflammation/ acute phase response and continued
catabolism.
Mediators of the Metabolic Response to
Injury
? `Classical Neuroendocrine
Pathways' of the stress
response consist of:
? Afferent nociceptive neurons
? Spinal cord
? Thalamus
? Hypothalamus
? and pituitary
Mediators of the Metabolic Response to
Injury.....
? Corticotrophin- Releasing Factor (CRF)- released from the hypothalamus
? Increases ACTH release- from the anterior pituitary.
? ACTH acts on the adrenals- increase the secretion of cortisol.
? Hypothalamic activation of the Sympathetic Nervous System-
? Release of Adrenaline and Glucagon.
? Intravenous infusion of a cocktail of these `counter-regulatory' hormones (glucagon,
glucocorticoids and catecholamine)-
? Results in many aspects of the metabolic response.
Mediators of the Metabolic Response to
Injury....
? Other mediators:
? Alterations in insulin release and sensitivity.
? Hypersecretion of prolactin and growth hormone (GH) in the presence of low circulatory
insulin-like growth factor-1 (IGF-1).
? Inactivation of peripheral thyroid hormones and gonadal function.
Neuroendocrine response to injury/critical
il ness
? Neuroendocrine response to severe injury/critical il ness is biphasic:
? Acute phase:
? Actively secreting pituitary and elevated counter-regulatory hormones (cortisol, glucagon,
adrenaline).
? Changes are thought to be beneficial for short term survival.
? Chronic phase:
? Hypothalamic suppression and low serum levels of the respective target organ hormones.
? Changes contribute to chronic wasting.
Immunological changes to injury/critical
il ness
? Innate immune system (principally macrophages) interacts in a complex manner with the
adaptive immune system (T cells, B cells):
? Also affects the metabolic response to injury.
? Pro-inflammatory cytokines (IL-1/ TNF/ IL-6 and IL-8):
? Produced within the first 24 hours of injury.
? Act directly on the Hypothalamus-
? Cause pyrexia.
? Augment the hypothalamic stress response.
? Act directly on skeletal muscle- induce proteolysis.
? Act on liver- Induce acute phase protein production.
? A complex role in the development of peripheral insulin resistance.
Immunological changes to injury/critical
il ness.....
? Endogenous Cytokine Antagonists enter the circulation:
? Within hours of the Upregulation of Pro-inflammatory Cytokines.
? e.g. interleukin-1 receptor antagonist [IL-1Ra] and TNF-soluble receptors [TNF-sR-55 and 75].
? Act to control the pro-inflammatory response.
? A complex adaptive changes includes:
? Development of a Th2-type counter-inflammatory response.
? Regulated by IL-4, -5, -9 and -13 and transforming growth factor beta [TGF].
? If accentuated and prolonged in critical illness- characterized as the CARS.
? Results in immunosuppression- increased susceptibility to nosocomial infection.
Immunological changes to injury/critical
il ness....
? Duration and magnitude of acute inflammation as wel as the return to
homeostasis are influenced by-
? Specialized proresolving mediators (SPM)- include essential fatty acid-derived
lipoxins, resolvins, protectins and maresins.
? Uptake and clearance- of apoptotic polymorphonuclear neutrophils and microbial
particles
? Reduce- proinflammatory cytokines and lipid mediators
? Enhance the removal of cel ular debris.
Immunological changes to injury/critical
il ness.....
? Systemic inflammatory response syndrome following major injury:
? Is driven initially by proinflammatory cytokines (e.g. IL-1, IL-6 and TNF).
? Is fol owed rapidly by increased plasma levels of cytokine antagonists and
soluble receptors (e.g. IL-1Ra, TNF-sR).
? If prolonged or excessive may evolve into a counterinflammatory response
syndrome.
The `Ebb and Flow ' model of metabolic
response
? Natural physiological response to injury includes:
? Immobility/rest
? Anorexia
? Catabolism
? Sir David Cuthbertson divided the metabolic response to injury:
? Into `ebb' and `flow' phases
Ebb phase
? Begins at the time of injury and lasts for approximately 24?48 hours.
? Characterized by-
? hypovolemia/ decreased BMR/ reduced cardiac output/ hypothermia and lactic acidosis.
? Predominant hormones regulating the ebb phase- catecholamines/ cortisol/ aldosterone.
? Magnitude of response depends on:
? Degree of blood loss.
? Stimulation of somatic afferent nerves at the site of injury.
? Main physiological role of the ebb phase:
? Conserve both circulating volume and energy stores for recovery and repair.
Flow phase
? Following resuscitation, ebb phase evolves into a hypermetabolic flow phase.
? This phase involves:
? Mobilization of body energy stores- for recovery and repair
? and subsequent replacement of lost or damaged tissue.
? Characterized by:
? Tissue edema (from vasodilatation and increased capil ary leakage)
? Increased basal metabolic rate (hyper metabolism)/ Increased cardiac output
? Raised body temperature/Leukocytosis
? Increased oxygen consumption
? And increased gluconeogenesis.
Flow phase.......
? Flow phase may be subdivided into:
? Catabolic phase
? lasting approximately 3?10 days.
? Increased production of counter-regulatory hormones (catecholamines, cortisol, insulin and glucagon) and
inflammatory cytokines(e.g. IL-1, IL-6 and TNF).
? Significant fat and protein mobilization- significant weight loss and increased urinary nitrogen excretion.
? Increased production of insulin- associated with significant insulin resistance and poor glycemic control.
? Increased risk of complications- further aggravate the neuroendocrine and inflammatory stress responses and creates
a vicious catabolic cycle.
? Anabolic phase
? may last for weeks if extensive recovery and repair are required fol owing serious injury.
Key Catabolic Elements of the Flow Phase
? During the response to injury, not al tissues are catabolic.
? Essence of coordinated response is-
? Reprioritise limited resources away from peripheral tissues towards key viscera and wound.
Key Catabolic Elements of the Flow Phase
? Hypermetabolism:
? Caused by an acceleration of energy-dependent metabolic cycles.
? limited in modern practice on account of elements of routine critical care.
? Skeletal muscle wasting:
? Provides amino acids for the metabolic support of central organs/tissues.
? Mediated at a molecular level- by activation of the ubiquitin?proteasome pathway.
? Can result in-
? Immobility
? Contribute to hypostatic pneumonia
? If prolonged and excessive- leads to death
Key Catabolic Elements of the Flow Phase
? Hepatic acute phase response:
? Represents a reprioritisation of body protein metabolism towards the liver and is characterised by:
? Positive reactants (e.g. CRP): plasma concentration
? Negative reactants (e.g. albumin): plasma concentration
? Insulin resistance
? Fol owing surgery or trauma- hyperglycemia develops as a result of
? Increased glucose production
? Combined with decreased glucose uptake in peripheral tissues.
? Decreased glucose uptake is a result of insulin resistance which is transiently induced.
CHANGES IN BODY COMPOSITION FOLLOWING
INJURY
? Catabolism:
? Decrease in fat mass and
skeletal muscle mass
? Body weight may
paradoxical y increase
? Expansion of extracellular
fluid space
Avoidable factors that compound the
response to injury
? Continuing haemorrhage
? Hypothermia
? Tissue oedema
? Tissue underperfusion
? Starvation
? Immobility
This post was last modified on 07 April 2022