33B. Autointoxication ✅ Flashcards
Definition of autointoxication
Endogenic toxicosis = self-poisoning
Internal source is causing a poisoning
7 types of autointoxication
- Disorder of intermedier metabolism
- Retention autointoxication
- Hepatic autointoxication
- Putrid autointoxication
- Abnormal direction of metabolism
- Enterogenic autointoxication
- Resorption autointoxication
/1. Disorder of intermedier metabolism as type of autointoxication
The transformation of a substance at a certain step of the intermediate metabolism gets stuck
No pathological pathway !
Diabetic autointoxication. Ketosis
- “diabetic toxins”: ketone bodies are accumulated with a non-treated diabetes mellitus type 1: acetoacetate, beta-hidroxi-butirate, acetone
- prolonged fasting (keto-diet)
- ketone bodies are produced in the mitochondria of the hepatocytes from acetyl-CoA
- result: ketone toxicosis = ketosis
- ketone bodies and unprocessed fatty acids are decreasing the blood pH: ketoacidosis (metabolic acidosis)
Diabetic autointoxication (ketosis). Symptoms
- nausea and vomiting, pronounced thirst, excessive urine production and abdominal pain
- acetone-breath
- dehydration - dry mouth, decreased skin turgor
- tachycardia and low blood pressure
- cerebral edema, which may cause headache, coma, loss of pupillary light reflex and progress to death
Pancreas fibrosis in dog
Diabetic autointoxification
- pancreas isn’t smooth, looks granulated
/2. Retention autointoxication. Meaning. Examples
The end products of normal metabolism are not excreted
Uremia. Uricosis. Icterus
Retention autointoxication. Uremia. Definition
Retention of various solutes that would normally be excreted by the kidneys, mainly
creatine, creatinine, urea, urine acid (birds)
Also hyaluronic acid, guanidine, guanidinoacetate, oxalate, SDMA (symmetrical dimethylarginine)
Complications of uremia
- vascular damage -> haemorrhages, edemas
- electrolyte abnormalities
- renal osteodystrophy
- multiorgan failure
Symptoms (and pathological lesions) of uremia
- commonly in cats: ulcers in the mouth (urea from blood gets excreted to mucous membranes; urea will be broken down by bacteria to ammonia, which will damage mucosal cells -> necrosis on mucosal surface
- damage of stomach mucosa
- uremia encephalopathy (dilated blood vessels, edema)
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Uricosis in birds
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Granulomas in uricosis
Uric acid crystals act as foreign body —> granulomas
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Uricosis.
Uric acid crystals act as foreign body —> granulomas
/3. Hepatic autointoxication
Hepatic parenchyma damaged (infection/poisoning/mechanical effect) —> fibrosis or cirrhosis
Fibrosis is followed by connective tissue proliferation
Cirrhosis = necrosis + regeneration + connective tissue proliferation
Systemic consequences:
- bilirubin retention
- gastro-enterogen autointoxication. Ammonia toxicosis. Hepatoencelopathy
Liver detoxification pathways
Phase 1
- oxidation, reduction and hydrolysis
- cytochrome P450 enzymes or Mixed Function Oxidase (MFO)
- membrane, hepatocyte
- chemical toxins
Phase 2
- conjugation (cystein, glycin, sulfur) to enable water solubility
- bile excretion
- urine excretion
Toxic effect of bilirubin
- bilirubin is toxic in most biological systems tested
- several mechanism have been suggested for this toxic effect, including inhibition of enzyme systems and inhibition of cell regulatory reactions (protein/peptide phosphorylation)
- serum level of unconjugated bilirubin exceeds the albumin binding capacity —> bilirubin diffuses into the CNS —> permanent neurological damage or death
- bilirubin encephalopathy with kernicterus
- bilirubin-induced neurologic dysfunction (BIND): hypotonia, hypertonia, opisthotonus, retrocollis
BIND - ?
Bilirubin-induced neurologic dysfunction
/4. Putrid autointoxication
hystolyses produces toxin protein derivates (neurin, muscarin, mydatoxin = ptomains. Gangrene (tissue level). Inflammation + gangrene —> ichorous inflammation
—> sapraemia
2 major types of gangrenes
Dry gangrene and wet gangrene
Dry gangrene
Dry gangrene (gangrena sicca)
- Form of coagulative necrosis
- Affected part is dry, shrunken and dark reddish-black (because of haemostasis).
- Drying out prevents putrefaction
- With time lesion will separate from the body — autoaputatio
Histology of gangrena
- shrunk cells
- hyperchromativ necked (kariopycnosis)
- cells are integral
- lack of autolysis, heterolysis
Wet gangrene
- damaged tissue can’t dry out
- tissue is infected by saprogenic/saprophytic bacteria (e.g. Clostridium perfrigens or Bacillus fusiforms)
- toxic products formed by bacteria are absorbed, causing systemic manifestation of sepsis
- the affected part is edematous, soft, putrid, rotten and dark
/5. Abnormal metabolism
Porphyria — is a condition when during the production of haemoglobin instead of the normal protoporphyrin 3 isomer the useless and toxic isomer 1 is being produced
(example for abnormal metabolism)
/6. Enterogenic autointoxication, enterotoxaemia
Bacterial toxins produced inside the intestines cause an intoxication
Toxins were not just swallowed, but produced inside of the guts!!!
Examples of Enterogenic autointoxication, enterotoxaemia
- acute bovine pulmonary emphysema and edema (ABPEE)
L-tryptophan -> 3-methylindole - equine grass sickness (Clostridium botulinum?)
- infectious necrotic enteritis of piglets and chickens: Clostridium perfrigens
- rabbits: E.coli, Clostridium perfrigens, Clostridium spiroforme
Toxic colon
- the colon’s function is to prevent the absorption and facilitate the elimination of toxins with the feces
- toxins in the feces: indol, skatol, phenol, methylmercaptan, urobilin, histidine, ammonia, putrescine, neurin, cadaverin, butyric acid, cholin, methylguanidine
- constipation causes intestinal autointoxication/toxic colon
/7. Resorption autointoxication
Rupture, perforation or arrodation of the stomach or intestines will release content to the peritoneum, toxic compounds will be absorbed to the blood stream
Digested food + enzymes + blood + profuse bacterial contamination
Morphological complications of the autointoxication
- main affected organs: liver, myocardium, kidney, brain
- hydronic or vascuolar degeneration: histopathologically large cytoplasm: swelling, enlarged mitochondria
- toxic hepatopathy
- toxic myodegeneration
- toxic nephropathy
- toxic encelopathy
- DIC (disseminated intravascular coagulopathy/microthrombosis) -> vasculitis
What’s the connection to autointoxication?
Haemorrhages are common in case of toxic material going through the body. Mainly haemorrhages happen under serous surfaces and often in the heart (lots of blood + pressure)
DIC
