[B] 1.11 Autointoxication Flashcards
Autotoxication AKA =
Autotoxaemia
Define autointoxication
- Poisoning of the body with endogen toxins
- Toxins are produced during the process in different diseases
Causes of autointoxication
- Normal metabolism gets stuck - accumulation of metabolites
- Normal metabolites not excreted
- Abnormal metabolism
- Decreased function of an organ
- Histolysis/heterolysis by gangrene
- Enterogenic autointoxication
- Absorbed metabolites from special cases
Diabetic autointoxication
- “Diabetic toxins”: Ketone bodies
- Ketone bodies produced during:
- Fasting
- Carb. restrictive diets
- Starvation
- Prolonged exercise
- Type-1 diabetes mellitus
List the ketone bodies
- Acetoacetate
- B-hydroxybutyrate
- Acetone
Ketosis
Metabolic state where most of the body’s energy comes from ketone bodies in the blood
Diabetic ketoacidosis (DKA) symptoms
- Nausea + vomiting
- Thirst + excessive urine production
- Abdominal pain
- Dehydration
- Tachycardia
- Low BP
- Cerebral oedema
What is shown?
Pancreas fibrosis
List the pathological findings from diabetic autointoxication
- Pancreas fibrosis
- Lipidosis in the liver
- Brain oedema
What is shown?
Lipidosis of the liver
What is shown?
Brain oedema
Retention autointoxication
- Develops with excretory organs
- Accompanied by a delay in metabolic product removal
- Kidney failure = Uraemia
- Uricosis
- Icterus (hepatopathy)
Uraemic autointoxication is characterised by…
Retention of various solutes that would normally be excreted by the kidneys
List some uremic toxins/retention solutes
- Creatine
- Creatinine
- Urea
- Uric acid
List the classifications of uremic toxins
- Low-molecular-weight water-soluble uremic toxins
- Protein-bound solutes
- Middle-molecular-weight molecules
Complications of uremic toxins
- Seizure, coma, cardiac arrest, death
- Spontaneous bleeding
- Subdural hematoma
- Electrolyte abnormalities (hyperkalaemia, metabolic acidosis)
What is shown?
Uremia (Kidney fibrosis, Dog)
Hepatic autointoxication examples
- Hepatitis
- Hepatosis
- Tumour
- Fibrosis
- Cirrhosis
Hepatosis
Degeneration of the liver
Hepatic fibrosis
Necrosis, scar formation
Cirrhosis
- Generalised formation of scar tissue associated with liver cell nercrosis
- Ineffective regenerative liver cell nodules
Give the effect of cirrhosis
- Retention of the bilirubin
- Decreased detoxification of the GI toxins (enterogen autointoxication)
Impaired hepatic detoxification refers to…
- Decreased phase I and/or phase II enzyme activity
- Levels of hepatic detoxification enzymes decreased
Phase one of detoxification consists of…
- Oxidation
- Reduction
- Hydrolysis
Phase I detoxification is catalysed by enzymes referred to as…
Cytochrome P450 enzyme group/Mixed Function Oxidase enzymes (MFO)
- Located in the membrane of the liver
Phase II of detoxification
Conjugation pathway
- Liver cells at substances to a toxic chemical/drug
- Renders the chemical less harmful
- Excreted from the body via bile/urine
Toxic effect of bilirubin
Inhibition of :
- Enzyme systems
- Cell regulatory reactions
Toxic effect of bilirubin in the brain
- If serum bilirubin > albumin binding capacity
- Bilirubin → CNS
- Permanent neurological damage/death
Bilirubin encephalopathy with kernicterus
Kernicterus: Etymology
“Yellow Kern”
Refers to an anatomic diagnosis made at autopsy
BIND
Bilirubin-induced neurologic dysfunction
- Clinical signs associated with bilirubin toxicity
Give some clinical signs associated with BIND
- Hypotonia → Hypertonia
- Opisthotonus
- Retrocollis
Impaired hepatic detoxification can result from…
- Exposure to food additives/solvents/pesticides/heavy metals
- Viral infections
- Restricted bile flow
- Old age
- Affects phase I enzymes
- Decreased blood flow to liver
Hepatic autointoxication - Complications
- Presence of chronic fatigue
- Depression
- Headaches, digestive disturbances
- Mental confusion
- Mental ilness
Histolysis by gangrene =
Putrid intoxication
Gangrene
A variety of necrosis
(Ichorous inflammation)
Give the varieties of gangrene
- Dry
- Wet
- Gas
- Internal
Dry gangrene
- Develops in ischemic tissue - Low blood supply
- ↓ Oxygen = limited putrefaction/bacterial growth
- The affected part is dry and shrunken
- Leads to autoamputation of affected area
Wet/infected gangrene
- Thriving bacteria
- Poor prognosis
- Free communication between: Infected fluid ⇔ circulation
- Can lead to sepsis
In wet gangrene, the tissue is affected by…
Saprogenic microorganisms
Causes tissues to swell and emit a smell
Give the fate of the toxins produced by the wet gangrene bacteria
- Necrotoxins are absorbed
- The systemic manifestation of sepsis
- Death
Describe clinical signs of wet gangrene
Affected part:
- Edematous
- Soft
- Putrid
- Rotten
- Dark
What is Porphyria/porphyrias?
A group of rare diseases in which porphyrins accumulate with high metabolism
Enterogenic autointoxication, enterotoxaemia
Absorbed decomposition products from GI system
E.g Grass fever; Grass sickness: C. botulinum
Intestinal autointoxication/Toxic colon
- Colon’s main role is toxin elimination via faeces
- Faecal toxins: Indol, skatol, phenol, urobilin
- Constipation → Intestinal autointoxication
Absorbed metabolites from special cases: Examples
- Arrodated stomach
- Ruptures
- Perforations
Autotoxaemia example
DIC (Disseminated intravascular coagulopathy)
