Gastrointestinal Flashcards
What is the effect of increased parasympathetic tone on gastrointestinal contractions?
May cause segmental contractions which inhibit progressive motility.
Increase exocrine gland secretion.
How do you distinguish the small colon on palpation?
Presence of faecal balls and an antimesenteric band that is palpable along the length of this segment if it is impacted.
Which electrolytes are lost in large volumes of gastric reflux or diarrhoea?
Na, K, Ca, Mg and HCO3
What are the potential mechanisms for increased lactate concentration in cases of colic?
- Large colon ischaemia
- Reduced perfusion to peripheral tissue due to hypotensive shock
- Generalised intestinal ischaemia may result in absorption of lactate from the lumen
- Increased blood viscosity reduces perfusion of capillary beds, exacerbating ischaemia and tissue hypoxia.
If oesophageal rupture is suspected or aspiration is a possibility which contrast material should be used for a contrast oesophogram?
Iodinated organic compounds in an aqueous solution should be used instead of barium.
What are the sites for the FLASH U/S examination of the abdomen?
Ventral abdomen, gastric window, spleno-renal window, left middle third of the abdomen, duodenal window, right middle third of the abdomen and thoracic window.
For an oral glucose absorption test, how much glucose is given, at what time point and what level should the peak be in blood glucose be, and what are the different levels of malabsorption cut offs?
1g/kg of d-glucose as a 20% solution in water via NGT
Peak at >85% above baseline glucose between 90-120min
Complete malabsorption is a peak <15% above resting,
Partial malabsorption is between 15-85% above resting.
What are the benefits of a xylose absorption test over a glucose absorption test and how is the protocol different?
d-Xylose absorption is not confounded by hormonal effects of mucosal metabolism of glucose as the glucose absorption test is.
Protocol is: 0.5g/kg d-xylose as a 10% solution; peak is between 60-90min but is a concentration between 20-25mg/dl.
What effects do the normal diet have on results of an oral glucose absorption test or an oral xylose absorption test?
OGAT: higher peaks in horses eating grass/hay compared with concentrates and from those at pasture compared with stabled.
OXAT: higher peaks in horses fed low-energy diet such as alfalfa chaff than those fed high-energy diets such as oat chaff, oats and corn.
List tests for assessing gastric emptying
- Contrast radiography in foals
- Nuclear scintigraphy for liquid or solid phase emptying
- Acetaminophen absorption and measurement in serum
- 13C-octane acid breath test using a labelled test meal and detection of the novel isotope in breath.
List the intestinal barriers against pathological invasion at the varying cellular levels.
Epithelium: tight junctions and mucous layer
Macrophages: resident macrophages in the lamina propria, submucosa and intestinal lymphoid organs are among the first to respond to infection.
Describe the events that lead to intestinal inflammation with epithelial breach.
Breach of the mucosal barrier initiates an inflammatory response through synthesis of pro-inflammatory chemokines (IL8) and cytokine (TNFα, arachidonic acid metabolites) by epithelial cells which then trigger influx of neutrophils and other leucocytes into the tissue.
Mast cells are sentinel cells that sense microbial invasion and release TNFα.
Macrophages within the lamina propria, submucosa and intestinal lymphoid tissue activate CD14 TLR4 complex which initiates transcription of TNFα and IL1β which synergise with LPS to amplify the macrophage response.
Once initiated, TNFα, IL1β and other proinflammatory products of neutrophils, monocytes, mast cells and eithelial cells amplify the inflammatory response, in part through release of nitric oxide and other nitrogen radicals which are microbicidal but also vasoactive.
List the four important changes that occur in the intestinal vasculature in response to inflammation.
- Alteration of blood flow (initially increased, then decreased due to increased viscosity with fluid loss and oedema, increased leucocyte margination, platelet adhesion etc)
- Increased vascular permeability (due to histamine, leucotrienes, prostaglandins and other inflammatory mediators cause endothelial cell contraction, creating leaky gaps)
- Increased adhesiveness of endothelial cells, leucocytes and platelets (cytokines stimulate endothelial cells to express adhesion molecules that support adhesion of leucocytes and platelets.
- Exposure of the basement membrane and activation of the complement, contact and coagulation cascades. (adhesion to the exposed basement membrane enables exposure of neutrophils and platelets to mediators of inflammation which activates the cells to release oxidants and proteases that injure the endothelium and can cause irreparable harm to the microvasculature). Marginated neutrophils begin to transmigrate between endothelial cells and this, if not closely regulated can worsen vascular leakage.
Why is neutrophil depletion considered protective in some models of GIT inflammation?
During the acute response neutrophils are activated to release products that are not only lethal to pathogens and proinflammatory but are also damaging to host cells and tissues.
What are the most potent stimuli for neutrophil activation at the site of inflammation?
Complement (specially C5a), cytokines (TNFa and IL1B), platelet activating factor (PAF), immune complexes and bacterial products
What are the main regulators/stimulators of mast cells?
Complement fragments (C3a, C5a and C4a) Neural pathways which respond to enteric pathogen invasion
What are some important roles of mast cells during intestinal inflammation?
- First line defense at epithelial barriers
- When activated the release histamine, proteases, heparin and cytokines, as well as inflammatory mediators including prostaglandins, PAF and leucotrienes.
- On the vasculature they increase endothelial permeability and cause vasodilation
- Mast cell derived mediated enhance epithelial secretion, including the mast cell protease tryptase which regulates GIT physiologic responses during inflammation, including intercellular junction integrity, motility and pain responses.
- Mast cell products alter intestinal motility, generally increasing it to enable expulsion of intestinal contents.
- Mast cell derived leucotrienes and TNFa have a crucial role in host defence against bacterial pathogens, including neutrophil recruitment, regulating dendritic cells and adaptive immune responses.
- Mast cells are phagocytic and can act as antigen presenting cells.
What is the function of complement fragments?
During activation of the complement cascade, soluble fragments of C3, C5 and C4 (C3a, C5a and C4a) are liberated. These anaphylatoxins are chemotactic for neutrophils, and activate neutrophils and mase cell degranulation as well as stimulating ROS.
What is the basic mechanism behind ischaemia-reperfusion injury?
Reperfusion of ischaemic tissue is associated with platelet and neutrophil clumping in the small vessels of the mucosa which can impede blood flow. Platelets are activated and adhere to exposed basement membrane and activated endothelial cells and provide a surface for leucocyte adhesion. The accumulation of platelets and leucocytes reduces vessel diameter and blood flow while potentiating local coagulation and thrombus formation. Various factors (histamine, leucotrienes, prostaglandins, thromboxane etc) from the activated leucocytes have a role in regulating local perfusion during inflammation. In addition, nitric oxide is a potent regulator of blood flow. However, many of the mediators affecting perfusion also affect endothelial permeability, altering osmotic and hydrostatic balance and tissue oedema, so in extreme cases local and systemic coagulopathies initiated by the vascular injury and absorption of microbial products and inflammatory mediats induce a hypercoaguable state and exacerbate thrombus formation and tissue injury/infarction
How does neutrophil migration damage endothelial and epithelial barriers?
To facilitate neutrophil migration to the site of inflammation they release serine proteases and metalloproteinases to liquefy tissue matrix proteins that make up intercellular junctions. These degradative enzymes are particularly damaging to basement membranes and the cellular barriers of the endothelium. However a similar effect occurs with the epithelium - TNFa and IFNy from activated neutrophils increases the permeability of tight junctions of enterocytes. Subepithelial accumulation of neutrophils can lead to deadhesion of the epithelial cells from the basement membrane and mild to severe ulceration. The end result is PLE and absorption of bacterial cell wall constituents.
What factors are thought to affect motility during diarrhoea?
- Invasive bacteria cause rapid bursts of motor activity in the colon that appear to decrease transit time through the large intestine.
- Absorption of endotoxin and release of inflammatory mediators such as prostaglandins disrupts the motility patterns of the large intestine, resulting in less coordinated contractions.
What are phagocyte derived reactive oxygen metabolites and what effects do they have on tissue?
Phagocytes produces superoxide radicals as a host defense mechanism to kill invading microorganisms. During inappropriate stimulation, as can occur with inflammation, trauma or ischaemia-reperfusion, increased levels of toxic oxygen species are produced causing marked tissue damage. Activated phagocytes secrete peroxidase enzymes into the extracellular space, which catalyse oxidation of Cl to yield HOCl which is 100-1000 times more toxic than O2- and is a non-specific oxidising and chlorinating agent that reacts with amines to form N-chloramines. The end result is marked tissue damage and altered permeability.
In what conditions is the GIT permeability to endotoxin/bacteria increased?
- Strangulating obstruction and bowel infarction
- Inflammation eg enteritis or colitis
- Bacterial overgrowth
- Intraluminal acidosis (eg grain poisoning/overload)
Which cytokines are of interest in the pathogenesis of endotoxaemia?
TNFa, the interleukins, chemokinse and growth factors such as granulocyte-monocyte colony stimulating factor.