B33 - Autointoxication

Question 1

What is autointoxication?

Answer 1

Also called autotoxaemia.
It is poisoning of the body by toxic substances that are produced within it, a self-poisoning.
It is an endogenous toxicosis.
There are 7 different types of autointoxication

Question 2

Name some general causes for autointoxication:

Answer 2

1. Retention of metabolic waste due to organ failure e.g., uremia in kidney failure, where nitrogenous wastes accumulate

2. Bacterial toxins from the gut in older pathology texts, autointoxication was linked to “self-poisoning” from intestinal putrefaction

3. Liver failure: where detoxification of ammonia and other metabolites is impaired

Question 3

Name the different autointoxications:

VERY IMPORTANT !!

Answer 3

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

Question 4

What is Disorder of intermedier metabolism autointoxication?

Answer 4

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

Question 5

Give an example of Disorder of intermedier metabolism autointoxication

Answer 5

Ketosis

Question 6

What is ketosis

Answer 6

The body breaks down too much fat, leading to excessive accumulation of ketone bodies (acetone, acetoacetate, and β-hydroxybutyrate)

Caused by:

• Energy demand is higher than glucose supply and the body uses fat instead.
• Fat is transported to the liver for energy production
• Glucose is low, so liver cannot metabolise properly, so the fats are converted into ketone bodies.
• The ketone bodies accumulated in the blood, urine, milk
• Leading to metabolic acidosis and toxicity

Question 7

Clinical signs of Disorder of intermedier metabolism autointoxication

Answer 7

• Nausea and vomiting
• Thirst
• Excessive urine production
• Abdominal pain
• Dehydration
• Tachycardia
• Cerebral oedema, causing headache.

Question 8

What is Retention autointoxication?

Answer 8

Normally excreted metabolic waste products accumulate in the body due to impaired elimination.Failure to excrete normal metabolic products results so they accumulate in the blood and tissues and act as toxins.

Caused by:

• Kidney dysfunction
• Liver dysfunction

Question 9

Give an example of Retention autointoxication

Answer 9

Uremic autointoxication

Question 10

What is uremic autointoxication?

Answer 10

Metabolic build up of Creatine, Urea and Uric acid.
Due to:

• kidney failure

Question 11

Consequences of Uremic autointoxication

Answer 11

1. Spontaneous bleeding/Vascular damage: The blood vessels are very sensitive to toxicosis. We see haemorrhages

2. Later, the uremia affects the circulatory system: Electrolyte abnormalities cause heart muscle damage, and the innervation of the heart is affected.
3. Multiorgan failure is the result !!:Due to the toxic build-up in the bloodstream

Question 12

What is hepatic autointoxication?

Answer 12

Liver fails to detoxidy or excrete toxins, leading to accumulation on blood and tissues.

Normally, the liver handles the metabolic waste through 2 phases:
1. Functionalization
2. conjugation

Question 13

What is phase I in regards to hepatic autointoxication

Answer 13

Modify toxins or metabolites to make them more chemically reactive, through oxidation, reduction and hydrolysis.
Mainly performed by cytochrome P450 enzymes in the liver.

• Result: Toxin becomes slightly more polar but may still be toxic

Question 14

What is phase II in regards to hepatic autointoxication

Answer 14

Make the reactive molecules water-soluble so they can be excreted, through conjugation with molecules and forming non-toxic and excretable compounds.

• Result: Metabolites are readily excreted in urine or bile

Question 15

Causes for hepatic autointoxication

Answer 15

- Infection: There is hepatitis
- Posining: A degeneration
- Mechanical effects: Such as tumours or biliary effects
- Severe liver disease: cirrhosis, hepatitis, massive hepatocellular necrosis.
- Obstruction of bile flow: cholestasis, bile duct obstruction.
- Metabolic defects: inborn errors of metabolism affecting the liver’s detoxification pathways.

Usually, these causes are mixed together. There is an intoxication of the deterioration of the hepatic tissue due to the toxic effect will induce inflammation, and inflammation will result in some sort of deterioration.

Question 16

Pathologcal findings in case of hepatic autointoxication

Answer 16

- Fibrosis:
- Cirrhosis: Necrosis and regeneration, and repair. Exclusive for the liver tissue.
- Generalised and systemic consequences:
1. Bilirubin-retention
2. Gastro-enterogen autointoxication
3. Ammonia toxicosis
4. Hepatic encephalopathy

Question 17

Give an example of hepatic autointoxication

Answer 17

Bilirubin accumulation

Question 18

What is Bilirubin accumulation?

Answer 18

Bilirubin is a product of hemoglobin breakdwon and is accumulated when:

• Excess production
• Impaired hepatic uptake
• Obsturction of bile flow

Question 19

What can accumulation of bilirubin cause?

Answer 19

BIND = Bilirubin-Induced Nerulogical Dysfunction

• A bilirubin accumulation in the brain
• Bilirubin build up crosses the BBB and is deposited in the neurons in the brain, causing neurotoxicity

Question 20

What is Putrid autointoxication?

Answer 20

Caused by the absorption of toxic products from decomposing or necrotic tissues, often in the presence of bacterial infection.

Sometimes called:

• septicaemic autointoxication
• gangrenous autointoxication

Question 21

What can cause Putrid autointoxication?

Answer 21

Wet gangrene and dry gangrene

Question 22

What is dry gangrene?

Answer 22

Tissue necrosis characterized by dry, shrunken, and dark-reddish-black tissue due to ischemia

With time, the lesions separate from the body, causing autoamputation.

• Usually seen in the distal parts.

Question 23

What is wet gangrene?

Answer 23

Severe form of tissue necrosis characterized by moist, soft, and foul-smelling tissue, usually due to bacterial infection combined with impaired blood flow
- Poor prognosis, due to the failure of separating the rotting tissue from the healthy

Question 24

What is Abnormal metabolism autointoxication

Answer 24

A self-poisoning caused by metabolic disturbances that lead to the accumulation of toxic substances within the body.

Question 25

Example of **Abnormal metabolism autointoxication**

Answer 25

**Porphyria**

Question 26

What is porphyria

Answer 26

Group of metabolic disorders caused by defective enzymes in the heme biosynthesis pathway, leading to accumulation of porphyrins or their precursors, which act as endogenous toxins Caused by: - Normally **protoporphyrin isomer type III** is produced, but this is blocked. - **Protoporphyrin isomer type I** isomer is produced, causing failure of heme confersion and accumulation of heme in blood, tissue and urine ## Footnote ***Porphyria is mainly due to genetic disorders.***

Question 27

What is **Enterogenic autointoxication**?

Answer 27

Self-poisoning that originates from the intestines, where toxins produced by gut bacteria are absorbed into the bloodstream. - Normally the liver detoxifies them, but with excess production, toxins enter the systemic circulation

Question 28

Infections/diseases prediposing to **Enterogenic autointoxication**

Answer 28

**- Clostridium perfringens:** Causes the infectious necrotic enteritis of piglets and chickens, due to intestinal overgrowth and toxin absorption. **- Clostridium botulinum:** Causes equine grass sickness, which is an acute, often fatal disease of horses caused by toxins affecting the autonomic nervous system, particularly the enteric nervous system

Question 29

What is **Resorption autointoxication**?

Answer 29

Self-poisoning that occurs when toxic substances produced within the body are absorbed into the bloodstream, overwhelming the body’s detoxification or excretion systems.

Question 30

Complications of any of the autointoxications

Answer 30

All of the types can result in several lesions: - Parenchymal organs are affected badly - Hepatoptahy - Vasculitis - Encepahopathy - **!! DIC (Disseminated Intravascular Coagulopathy) will always occur in the end !!**

Question 31

What is DIC?

Answer 31

**Disseminated Intravascular Coagulation** Formation of microthrombi, which consumes the platelets and blood clotting factors. - Resulting in a high risk of widespread bleeding.