Hepatic System Part 1

Liver

The largest internal organ. Consists of two main lobes separated by the hepatic vein. Located in the upper right corner of the abdomen.

Hepatic artery

Supplies 25% of the liver's blood flow and provides most of the oxygen required.

Portal vein

Drains most of the GI tract and supplies 75% of the liver's blood supply. Transports recently absorbed material from the intestines to the liver.

Homeostasis

The liver plays a major role in maintaining protein, carbohydrate, and lipid balance in the body.

What does the liver store?

Glycogen, vitamins and iron. Iron is predominantly recycled in the body

Blood cell production and breakdown

liver contains an extensive reticuloendothelial system

First pass metabolism

Liver cells metabolise, detoxify and excrete endogenous and exogenous compounds.

Liver disease diagnosis

Personal and family medical history and food/drink habits considered. Liver function tests, complete blood count tests, imaging scans and sometimes biopsies are done

Jaundice

A symptom of liver disease caused by high bilirubin levels

Functional reserve capacity

The liver has a large capacity to compensate for damage, with liver cancer patients surviving even with up to 95% of their liver removed.

Lifestyle changes to control symptoms of liver disease

Limiting alcohol, maintaining a healthy weight, increasing water intake and dietary fibre, decreasing fat, sugar and salt

Antiviral drugs

Used to treat hepatitis

Steroids

used to reduce liver inflammation

Hepatic portal hypertension

Causes liver damage, varicose veins, haemorrhoids, and oesophageal varices. Treated with blood pressure medication

Hepatitis strains

There are 5 strains (A to E), with hepatitis C being one of the most common

hepatitis C

Acute or chronic. Spread through contact with infected blood. No symptoms in early stages. Can cause permanent liver damage.

major causes of chronic hepatitis

Hepatitis B and C

interferon alfa (currently unlicensed)

Stimulates T cells and other immune cells to attack disease agents. May reduce risk of chronic infection if used to treat acute hepatitis C

ombitasvir with paritaprevir and ritonavir

inhibit wide range of both DNA and RNA viruses

sofosbuvir

inhibits NS5B protein of hepatitis C virus

Fatty liver disease

Can be alcoholic or non-alcoholic. Caused by fat build-up in liver → liver damage, cirrhosis and liver failure if unmanaged.

cirrhosis

degenerative liver disease causing scarring and liver failure

How does pioglitazone help treat advanced liver fibrosis?

Improves tissue sensitivity to insulin

What is pioglitazone?

Synthetic ligand for peroxisome proliferator-activated receptors (PPARs)

What do peroxisome proliferator-activated receptors (PPARs) do?

transcription factors which regulate glucose and lipid metabolism

Autoimmune hepatitis

The immune system attacks the liver, resulting in inflammation.

Primary biliary cirrhosis

Damage to the bile ducts in the liver causes bile build-up, potentially leading to cirrhosis and liver failure.

Primary sclerosing cholangitis

inflammatory condition causing gradual bile duct damage and blockage → liver bile build-up, cirrhosis or liver failure.

Prednisolone to treat autoimmune liver conditions

increases neutrophil concentration and decreases T/B cells, monocytes, eosinophils and basophils. Decreases cytokine release eg IL-2 and TNF-α

azathioprine

immunosuppressive agent which antagonises purine metabolism, inhibiting DNA, RNA and protein synthesis

vitamin E

potent antioxidant taken by patients with advanced liver fibrosis

Liver cancers

Develop in the liver, with hepatocellular carcinoma being the most common type.

secondary liver cancer

cancer which has metastasized to the liver. More common than primary liver cancer

hepatocellular carcinoma

typically develops as several small cancer spots, although it may also start as a single tumour

Monoclonal antibodies

Used for cancer treatment eg ipilimumab and tremelimumab

everolimus

Inhibits mammalian target of rapamycin (mTOR). Used to treat liver cancer

Cholestasis

Impairment of bile formation/flow

symptoms of cholestasis

fatigue, pruritus, dark urine, pale stools, jaundice and signs of fat soluble vitamin deficiencies

colestyramine

bile acid sequestrant used in cholestasis treatment

SSRIs eg sertraline

used to treat pruritus caused by jaundice