33B. Autointoxication ✅

Question 1

Definition of autointoxication

Answer 1

Endogenic toxicosis = self-poisoning
Internal source is causing a poisoning

Question 2

7 types of autointoxication

Answer 2

1. Disorder of intermedier metabolism
2. Retention autointoxication
3. Hepatic autointoxication
4. Putrid autointoxication
5. Abnormal direction of metabolism
6. Enterogenic autointoxication
7. Resorption autointoxication

Question 3

/1. Disorder of intermedier metabolism as type of autointoxication

Answer 3

The transformation of a substance at a certain step of the intermediate metabolism gets stuck

No pathological pathway !

Question 4

Diabetic autointoxication. Ketosis

Answer 4

• “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)

Question 5

Diabetic autointoxication (ketosis). Symptoms

Answer 5

• 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

Question 6

Answer 6

Pancreas fibrosis in dog
Diabetic autointoxification

• pancreas isn’t smooth, looks granulated

Question 7

/2. Retention autointoxication. Meaning. Examples

Answer 7

The end products of normal metabolism are not excreted

Uremia. Uricosis. Icterus

Question 8

Retention autointoxication. Uremia. Definition

Answer 8

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)

Question 9

Complications of uremia

Answer 9

• vascular damage -> haemorrhages, edemas
• electrolyte abnormalities
• renal osteodystrophy
• multiorgan failure

Question 10

Symptoms (and pathological lesions) of uremia

Answer 10

• 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)

Question 11

?

Answer 11

Uricosis in birds

Question 12

?

Answer 12

Granulomas in uricosis
Uric acid crystals act as foreign body —> granulomas

Question 13

?

Answer 13

Uricosis.
Uric acid crystals act as foreign body —> granulomas

Question 14

/3. Hepatic autointoxication

Answer 14

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

Question 15

Liver detoxification pathways

Answer 15

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

Question 16

Toxic effect of bilirubin

Answer 16

• 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

Question 17

BIND - ?

Answer 17

Bilirubin-induced neurologic dysfunction

Question 18

/4. Putrid autointoxication

Answer 18

hystolyses produces toxin protein derivates (neurin, muscarin, mydatoxin = ptomains. Gangrene (tissue level). Inflammation + gangrene —> ichorous inflammation
—> sapraemia

Question 19

2 major types of gangrenes

Answer 19

Dry gangrene and wet gangrene

Question 20

Dry gangrene

Answer 20

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

Question 21

Histology of gangrena

Answer 21

• shrunk cells
• hyperchromativ necked (kariopycnosis)
• cells are integral
• lack of autolysis, heterolysis

Question 22

Wet gangrene

Answer 22

• 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

Question 23

/5. Abnormal metabolism

Answer 23

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)

Question 24

/6. Enterogenic autointoxication, enterotoxaemia

Answer 24

Bacterial toxins produced inside the intestines cause an intoxication

Toxins were not just swallowed, but produced inside of the guts!!!

Question 25

Examples of Enterogenic autointoxication, enterotoxaemia

Answer 25

- 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*

Question 26

Toxic colon

Answer 26

- 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

Question 27

/7. Resorption autointoxication

Answer 27

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

Question 28

Morphological complications of the autointoxication

Answer 28

- 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

Question 29

What’s the connection to autointoxication?

Answer 29

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)

Question 30

DIC