Liver Flashcards
What is the liver?
The liver is a peritoneal organ positioned in the right upper quadrant of the abdomen. It is the largest visceral structure in the abdominal cavity, the largest gland in the human body and the second largest organ.
Liver Physiology
- Vascular function for storage and filtration of blood
- Metabolic and storage functions
o Synthesis and metabolism - Carbohydrates: The liver plays a central role in maintaining blood glucose levels. Following consumption of food, excess glucose can be stored within the liver as glycogen. This is stimulated by insulin release; glycogen is stored in the liver; participates in gluconeogenesis
- Fats: fatty acids- lipogenesis – lipolysis
- Proteins (proteins, clotting factors, angiotensin etc)
- Vitamins (A, D, E,K, B12, iron): The liver is important in the metabolic activation of Vitamin D
- Deactivation “waste” (toxic amino-acids, ammonia)
- Secretory functions
o Bile
o Bilirubin - Iron levels within the body need to be tightly regulated. Therefore, excess amounts must be stored in places such as the liver. Most iron within cells is stored in ferritin, a protein produced by the liver. All cell types within the liver can store iron however the majority is stored within hepatocytes.
Liver physiology in pregnancy
- Increased liver metabolism hence why different medication need to be altered
- Changes in liver enzymes
o Significant increase in alkaline phosphatase (2-4 fold) – placental production increase with each trimester
o Decrease in upper limit of the normal range for alanine transferase or aminotransferase (ALT or SGPT), aspartamine transaminase (AST), SGOT (Serum glutamic oxaloacetic transaminase) - Changes in protein concentration
o Decrease in total serum protein concentration (20-40% fall in serum albumin) - dilution due to increase of total blood volume
o Rise in fibrinogen, transferrin, caeruloplasmin, other specific binding proteins ie TBG and CBG
Investigations in liver disease
- Liver function tests (LFTs)
- Glucose
- FBC: Plts
- Clotting studies
- Hepatitis screen
- Auto-antibody screen
- Liver ultrasound
Liver disease
- Pre-pregnancy liver disease
o Hepatitis
o Chronic liver disease: could be related to alcohol
o Liver transplant
- Pregnancy related liver disease
o Obstetric cholestasis
o Pre-eclampsia
o Liver capsule haematoma
o HELLP syndrome
o Acute fatty liver of pregnancy
Intrahepatic Cholestasis of pregnancy
- Most common pregnancy-specific liver condition
- Generally, cholestasis can be of: obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications
- Cholestasis is the term used to characterise the disruption and reduction of the bile products from the liver and its flow to the intestine.
- Fetal risks may include spontaneous preterm birth, iatrogenic preterm birth and fetal death
- Maternal morbidity associated with sleep deprivation and malaise from itching
Bile acids
- Synthesised in the liver
- In the small intestine, bile acids emulsify dietary fats, lipids and fat-soluble vitamins
- Acting via a number of receptor-controlled pathways that impact cholesterol, lipid and carbohydrate homeostasis as well as the immune system
- Bile acids are extremely cytotoxic at low concentrations
- The liver takes up approximately 95% of bile acids with the remaining 5% lost in faeces
Aetiology of ICP
It is asserted that ICP pathogenesis involves a predisposition to the cholestatic effect of the increased circulating oestrogens and progesterones
Genetic factors
Hormones
Environment
Genetics aetiology
35% of patients with positive family history and 12% of parous sisters are affected (autosomal dominant sex-limited inheritance). No distinct male phenotype has been identified, although
related individuals often have gallstones.
• mutations of some of the hepatobiliary transporters (ABCB4, ABCB11). There appears to be variable severity of cholestasis in association with different homozygous and heterozygous mutations When mutations of these genes were identified, ICP occurred more frequently than expected.
• single nucleotide polymorphisms (SNPs), but this is not considered a mutation, just a variant of a peptide, so causing a smaller degree of risk
• These transporter
• Link to GDM and PET
Hormones aetiology
- With respect to ICP, serum levels of oestrogen and progesterone are highest during the third trimester when the disease usually presents a cholestatic effect of oestrogen administration, with effects seen on transporter expression and localization; FXR pathway can be directly inhibited by 17-estradiol-activated oestrogen receptor resulting in an inhibition of the transcription of ABCB11
- Elevated oestrogens are associated with significant impairment in suphation capacity (sulphation of bile acids is important in attenuating their cholestatic potential)
- COC pill may precipitate a similar syndrome (exogenous oestrogens) 15% (Williamson et al. 2004)
- A number of progesterone metabolites have been identified as capable of cross-talk with bile acid signalling pathways, thus having an impact on the cholestatic phenotype
- Progesterone metabolites impact hepatocellular bile acid influx by competitively inhibiting NTCP, and to reduce BSEP-mediated efflux.
- Certain metabolites also act as partial agonists of FXR, contributing to the cholestatic phenotype by desensitising FXR-regulated pathways
- Specific metabolites may serve as early predictive biomarkers as they are elevated prior to increased serum bile acids
Environment aetiology
• Winter has been associated with higher incidence of ICP (gut microbiome-low levels of vit D: vit D levels are associated with ICP and its degree of severity.
ICP increases the risk of
A spectrum of biliary disease that includes:
- Low phospholipid gallstones
- Recurrent ICP
- Biliary sludge
- Contraceptive-induced cholestasis (CIC)
- Non-alcoholic Cirrhosis
- Chronic hepatitis in later life (Non A; Non B Hepatitis)
- Type 2 diabetes
- Cardiovascular disease
- Cancer (biliary tree) – but very small risk
Symptoms of ICP
- Pruritus (typically from 28 weeks of pregnancy, often nocturnal)
- Dark urine: raised bilirubin
- Pale stools (steatorrhea)
- Jaundice (less commonly)
- Right Upper Quadrant (RUQ) Pain
- Urinary Tract infections?
diagnosis of ICP
- Initially by exclusion of other causes of pruritus
o Autoimmune hepatitis, Primary Biliary Cholangitis (PBS)
o EBV, CMV
o Gallstones
o Other dermatological conditions
o Concomitant existence with other diseases - Deranged liver function
o Raised serum bile acids (>10 or 14 mol/l)
o Raised ALT and AST (use pregnancy range)
o 5–10% have raised bilirubin - Liver scan
Maternal risks
- ? Vitamin K deficiency (malabsorption of fat soluble vitamins)
- ? Postpartum haemorrhage
- Increase in IOL
- High CS rates (10-36%)
- Sleep deprivation
- Mental health
