Alcohol Related Liver Disease Flashcards
Caoimhe
Functions of Liver (4)
- Metabolism: (of lipids, proteins, hormones, CHOs, drugs, toxins, foreign compounds)
- Synthesis: (of cholesterol, clotting factors, plasma proteins)
- Storage: (of glycogen, vitamins, minerals)
- Metabolism and excretion of bilirubin
4 Stages of ARLD
- Steatosis: fatty build up in liver
- Acute and chronic alcoholic hepatitis
- Fibrosis: any degree of scarring in liver
- Cirrhosis: due to long term damage, extreme scarring, will result in liver failure, irreversible
Why is the liver the major organ target of alcohol induced injury?
Because the liver is the main site of alcohol metabolism
What is steatosis?
Fatty build up in the liver, usually resolves upon cessation of alcohol consumption
What is fibrosis?
Fibrosis describes any degree of scarring in the liver. It can be reversed if aetiological agent is removed.
what is cirrhosis?
More extensive scarring accompanied with regenerative nodules
Pathogenesis of steatosis
- The hepatitis fatty acid (FA) pool is a balance of FA influx from diet, adipose tissue lipolysis, creation of new lipids and disposal of FAs.
- An increased uptake and reduced clearance of FAs leads to accumulation of lipids and development of steatosis.
- Alcohol interferes with lipid metabolism: the breakdown of alcohol by ADH releases NADH causing the cell to inhibit the breakdown of FAs while simultaneously to increase the synthesis of FAs, creating more lipids than needed and leading to a false sense of energy.
ARLD pathogenesis
- ADH pathways overwhelmed so alcohol oxidation by MEOS and catalase increases
- The MEOS and catalase pathways are more likely to produce harmful by-products that contribute to inflammation
ARLD pathogenesis expanded (3)
- Alcohol mediated liver steatosis
-
Inflammatory immune response and oxidative damage
3.Intestinal permeability and consequent intestinal microbiome changes
Intestinal permeability changes lead to an increased risk of ??
Infection (due to bacterial overgrowth) and pro inflammatory changes
ARLD risk factors (5)
- **Increased alcohol consumption
- obesity
- genetics**
- being african/hispanic
- being female
Signs and symptoms (7)
- Abdo pain and tenderness: inflammation of liver due to steatosis
- Dry mouth
- Anaemia: due to liver having an input in iron homeostasis
- Skin colour changes (jaundice in extreme cases): bruising due to lack of clotting factors, low platelet count, TPO synthesised in liver
-
Numbness in extremeties
6.Neurological problems: build up of toxins makes its way to brain - Thrombocytopenia: low platelet count due to TPO (thrombopoetin) being synthesised in liver
Diagnosis- Biochemistry(5)
- Liver panel done to assess liver function
- Liver enzymes AST:ALT ratio greater than 1 an indication of ARLD
- Raised GGT (liver enzyme) linked to ARLD
- Low albumin count in liver disease
- Increase in bilirubin
Diagnosis - Haematology (2)
1. FBC -> PLT levels
2. Clotting screen
3. Serum ferritin (increase with ARLD)
Diagnosis - Histo (1)
- Biopsy
In a biopsy what would you expect to see at steatosis?
Fatty deposits marked by areas of clearing
In a biopsy what would you expect to see at fibrosis?
Collagen deposition (staining changes)
In a biopsy what would you expect to see at cirrhosis?
Collagen deposition and changes to vasculature
Complications of ARLD (3)
- Portal hypertension
- Ascites
- Cancer
Portal Hypertension
What is it?
Increased pressure within the portal venous system
Portal Hypertension
Pathogenesis (4 steps)
- Cirrhosis and scarring of liver -> architectural changes
- Blood forced through smaller blood vessels
- Increased resistance
- Increased blood pressure
Ascites
What is it?
A condition where fluid collects in spaces within the abdo (especially the peritoneal cavity)
Ascites
Pathogenesis
- Portal hypertension and vasodilation combined with:
- Reduced plasma protein synthesis (esp albumin) and therefore reduced oncotic pressure
Ascites
Signs and symptoms (5)
- Abdo swelling
- Abdo discomfort
- Weight gain
- Early satiety
- Shortness of breath
Ascites
Complications (2)
- Abdo infection
- Hernia
Ascites
Treatment (4)
- Reduce alcohol intake
- Reduce salt and fluid intake
- Diuretics
- Fluid drains
Ascites
Diagnosis (2)
- Paracentesis: drain with needle. Sent to Micro to rule out infection and to Histo to rule out cancer.
- Imaging:MRI and CT
Cancer
How is treatment determined
By staging and grading with Barcelona staging
Cancer
Treatment (3)
- If HCC localised: surgical excision
- If cancer throughout liver but has not spread: transplant
- If cancer metastasised: chemo and supportive care
Cancer
Prognosis
- Poor but depends on stage of diagnosis
- Often aggressive due to quick doubling time of hepatocytes
Cancer
Diagnosis (4)
- Signs and symptoms overlap with ARLD
- ABnormal liver function tests and clotting times
- Histology
- Tumour markers: elevated AFP (alpha fetoprotein)
