Lab 8 Flashcards
Icreased parasympathomimetic effect
Neostigminum methylsulphuricum, physostigminum (Stigmosan inj.):
Local effect:
- increased smooth muscle contraction (increased peristalsis, and secretory function)
– increased intestinal metabolism causes increased gas formation and gas accumulation cranially from the effect
Systemic effect:
- Increased parasymathomimetic and acetylcholine effects – increased muscular (smooth muscle and striated also) irritability (i.e. treatment of myasthenia gravis)
Increased parasympatholytic effect
Atropinum-sulphuricum, N-butil scopolamine-bromide (Buscopan inj.)
Local effects: relaxing intestinal muscles (decreased peristalsis) and decreasing secretory function.
Systemic effect: decreased parasympathetic tone.
These parasympatholytic drugs should not be used in veterinary practice for the treatment of gastrointestinal hypermotility, and hypersecretion (for example in case of enteritis) due to the danger of intestinal bacterial overgrowth and absorption of toxic materials.
Increased sympathomimetic effect
Adrenalin (epinephrine)
Local effect: relaxing intestinal muscles, paralytic ileus.
Systemic effect: adrenaline is a stress mediator.
Increased sympathetic tone is generally caused by increased endogenous adrenalin production due to stress or pain (the consequence can be intestinal or ruminal atonia or even paralytic ileus). Adrenalin injection can save life! It is used for the treatment of severe anaphylactic shock, and for resuscitation in case of asystole to restart heart muscle contractions.
Local and general consequences of ileus
- Intestinal spasm onto the irritant (foreign body)
- water influx into the lumen of intestines
- aboraly from the foreign body intestines are empty, walls are attached to each other
- vessels of the intestinal wall are compressed at the site of ileus
- stasis (stagnant hypoxia) develops behind the block of the venous flow, and lack of blood (ischaemic hypoxia) after the block of arterial flow
- Local anaerobic glycolysis and local lactic acidosis at the site of ileus which leads to tissue necrosis and inflammatory process locally.
- Fluid accumulates in the intestine proximally from the block
- some water is filtrated through the vessels and can get into the abdominal cavity, causing ascites, septic peritonitis
- Some water is vomitted due to antiperistalsis or reflux
- Due to accumulation of the intestinal content, bacterial overgrowth develop. Gram -: endotoxins. Gram+: exotoxins
- Bacterial toxins and metabolic products cause further water influx into the intestinal lumen, aggravating dehydration
- metabolic products of bacteria and the increased metabolism of the intetinal wall cause increased gas accumulation in the loops proximally from the site of ileus
- intestinal damage can cause haemorrhage in the lumen, can lead to blood loss
- the patients du not eat: painfull abdominal cavity so there is stress and adrenalin effect. Due to adrenalin there is intestinal atonia and there is no stimulus for emptying the gall bladder - bad!
- in some chronic cases pancreatitis and liver damage may develop
- water loss due to profuse vomiting and water influx into the intestinal lumen cause haemoconcentration and hypovolemia, poor tissue perfusion and general anaerobic glycolysis and lactic acid production, and sometimes hypovolemic shock
- as a consequence of dehydration, GFR will decrease, decreased renal function (oliguria, prerenal azothemia may develop)
- hypokalaemia; cause muscle weakness, also in the resp. muscles which can lead to hypoxia and even death. Ventilatory failure, hyperkapnia, hypoxaemia will develop. May cause respiratory acidosis
- due to dehydration, metabolic and respiratory acidosis may develop, hypokalaemia, endotoxaemia and bacteriaemi causes shock, death.
-
Some clinical signs and complications of pancreatitis:
anorexia, depression, sevre abdominal pain (at the apigastrium), severe vomitting, exsiccocis, sometimes diarrhea, signs of heart failure, vasculitis, kidney failure, liver failure, dyspnoe, sometimes anemia and/or icterus, sometimes signs of peritonitis, paralytic ileus, septicaemia, DIC, multiorgan failure, abscess formation in the pancreas.
Haematological analysis of pancreatitis
polycythaemia (due to dehydration)
degradation of red blood cells (membrane damage due to high activated enzyme level in the blood, schysiscytosis, acanthocytosis)
anaemia (in chronic sever cases)
leukocytosis (or leukopenia in case of abscess)
neutrophilia (or -penia), left shift
leukemoid reaction
determination of pancreatic enzymes in the plasma
alpha-amylase activity
lipase activity
phospholipase-a2 activity
trypsinogene - /trypsine/ concentration (RIA or ELISA methods)
elastase concentration (RIA or ELISA methods)
Best is: pancreas specific lipase (PSL) (ELISA method)
Determinations of substrates in the plasma:
glucose concentration (IDDM)
concentration of electrolytes (Na+ , K+ , Cl- ) (alteration of isoosmosis, -ionia as a consequence)
alpha2-macroglobulin concentration (it can be decreased because this protein is able to bind to active pancreatic enzymes and deactivate them)
alpha1-antitrypsine concentration (it can also be decreased because of the intensive utilisation, as it is an antiprotease which defends the plasma from trypsine and other proteases)
triacylglycerol concentration (due to increased lipase activation, and/or IDDM)
Ca2+ concentration (Ca2+ can be depleted into the necrotised fat of the pancreas forming “soaps”, “liponecrosis pancreatica”)
kidney, liver parameters and total protein, albumin concentration should be measured in order to diagnose the effects of the complications.
Methods to measure alpha-amylase activity
Startch digestion test:
- Stain is absorbed to starch.
- In slightly alkalytic environment alpha-amylase in plasma sample digests starch to diglycerids during the incubation period and stain becomes free in the reagent.
- More stain gets free when alpha-amlyase is increased in the plasma sample.
p-nitrophenol method:
- p-nitrophenol is bound to oligosacharides.
- Alpha-amylase splits oligosacharides to smaller parts (disacharids, monosacharids).
- The reagent contains alphaglucoxidase and glucose will be produced as an end product.
- The oligosacharide bound pnitrofenol becomes free in the reagent. The increased intesitiy of yellow p-nitrofenol is proportional with amylase activity.
Increased alpha-amylase activity is found in the following cases:
- acute pancreatitis
- (acute, subacute) kidney failure: any kidney failure
- FIP (feline infectious peritonitis), and other immune-mediated diseases (macroamylasaemia),
- lymphoma, myeloma (macroamylasaemia),
- diabetes mellitus (macroamylasaemia),
- ileus, gastric or intestinal perforation
- parotitis,
- chronic enteritis.
determination of lipase activity
Turbidimetric method
- Most commonly used method done by spectrophotometer. Reagent contains triolein (lipid). Plasma lipase splits triolein to monoacylglycerols, which leads to decreased turbidity of the reagent. The decrease of the turbidity within a period of time is proportional with the lipase activity.
Increased lipase activity is found in case of:
- acute pancreatitis
- acute, subacute kidney failure
- ileus, gastric or intestinal perforation
- chronic enteritis.
How to determine Trypsine
TLI (Trypsine like immunoreativity)
TLI is a species specific parameter, which can be determined by RIA-method (radioimmunassay).
- Feature is that antibodies are produced against one part of trypsinogen (its hapten is common with trypsine’s). Antibodies marked by radioisotopes are bound to trypsinogen (trypsine) of the sample.
- The marked antibody-trypsinogen (trypsine) cause increased radioactivity that can be measured by specific analyser. Not only RIA, but also ELISA methods are available to determine TLI
Function of trypsinogen
Normally tripsinogen goes to the duodenum and is activated by enterokinase to be trypsine and is present in the plasma in a small proportion.
In case of pancreatitis more trypsinogen or active trypsine can get into the blood stream and the concentration will be 15 times more than the normal value (2,5-5 µg/l).
How is EPI developed
EPI is developed due to chronic necrotic or atrophic damage (caused by chronic inflammation, fibrosis, etc…) to the pancreas, or sometimes it is an inherited disease (pancreatic acinar atrophy=PAA, mostly in german shepherd dogs)..
