# data[].attributes.body
Cholestasis is a condition where bile cannot flow from the liver to the duodenum.

# data[].attributes.body
Cirrhosis is an irreversible distortion of normal liver architecture characterized by hepatic injury,
fibrosis, and nodular regeneration.

# data[].attributes.body
Liver is the largest internal organ and lies in the right hypochondrium.

It has 2 anatomical lobes & 8 segments divided by blood vessels

25% of heart bloods supply goes to the liver

# data[].attributes.body
Portal vein drains most of the GI tract and the spleen and then enters the Liver to give nutrient rich blood.

Hepatic artery is necessary for liver oxygenation and supplies the biliary system.

Liver acinus encompasses the liver tissue that is served by a single terminal branch of the hepatic artery

Zone 1 is best oxygenated & gluconeogenesis & urea

Zone 2

Zone 3 most remote from afferent vessel

Lobule = organization of hepatocytes into the hexagon

around is are the portal triads (made out of bile duct, portal vein, hepatic artery)

# data[].attributes.body
Hepatocytes:

The functional cells of the liver. They are part of the Acinus

apical, basolateral, lateral

Endothelial cells --> make up the walls of the sinusoids

Kupffer cells --> specialized Macrophages

Stellate cells/Lipocytes --> fat-storing cells involved in vitamin A metabolism and lie between hepatocytes and endothelial cells

Space of Disse --> space between sinusoid channels and hepatocytes and it contains a mixture of cell matrix and stellate cells.

# data[].attributes.body
Protein Metabolism

Main site of protein synthesis

Albumin synthesis

Degradation of amino acids --> conversion into urea --> excreted by kidneys

Carbohydrate metabolism

Glucose and blood sugar homeostasis

Storage of glycogen

Can be broken down and stored during fasting

Lipid metabolism

Metabolizes VLDL & HDLs

Cholesterol synthesis

# data[].attributes.body
The liver stores vitamin A, D (also conversion), B12, glycogen

# data[].attributes.headline
Synthesis & Secretion of plasma proteins and hormones

# data[].attributes.subject
Synthesis & Secretion of plasma proteins and hormones

# data[].attributes.body
The liver has important roles in maintaining plasma oncotic pressure (serum albumin), coagulation (clotting factor synthesis and modification), blood pressure (angiotensinogen), growth (insulin-like growth factor-1), and metabolism (steroid and thyroid hormone–binding proteins).

# data[].attributes.body
Kupffer cells

The Kupffer cells have phagocytic and endocytic functions. The liver helps remove bacteria and antigens that breach the defences of the gut to enter the portal blood.

Filtering of blood:

liver breaks down drugs/hormones/alcohol

CYP450 enzymes

# data[].attributes.body
Synthesis ---> transport out of hepatocyte --> bile canaliculus --> biliary tract --> bile duct excretion --> terminal ileum reabsorption

# data[].attributes.body
Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids, and conjugated bilirubin

Bile formation requires the uptake of bile acids and other ions. Bile acids are also synthesized in hepatocytes from cholesterol

Bilirubin is produced mainly from the breakdown of mature red blood cells by Kupffer cells in the liver and reticuloendothelial system

Steps bilirubin secretion:

Reticuloendothelial system uptake of heme

Bilirubin release into plasma & take up by albumin

Reaches the liver à hepatocyte uptake of bilirubin

Hepatocyte conjugates with glucuronic acid --> conjugates secreted into bile

Function of conjugation

Conjugated bilirubin is metabolized and absorbed in the colonic epithelium = enterohepatic circulation!

# data[].attributes.body
Liver function tests

serum albumin and bilirubin

Prothrombin time

Liver biochemistry

Serum bilirubin

serum AST & ALT

Aminotransferases AST & ALT are contained in hepatocytes and leak into the blood when liver cells are damaged

Serum alkaline phosphatase ALP

Viral markers

Urine tests

bilirubin

Imaging techniques

Ultrasound

CT

MRI

X-ray

Upper GI endoscopy

Endoscopic retrograde cholangiopancreatography

Angiography

Liver biopsy

Histological examination of the liver

# data[].attributes.body
a.	Altered carbohydrate & lipid metabolism
b.	Loss of solubilization & storage function
c.	Impaired drug detoxification
d.	Diminished synthesis & secretion of plasma proteins
e.	Na+/water balance

# data[].attributes.body
Acute Liver disease:

May be asymptomatic

Malaise, anorexia, fever, jaundice

Chronic liver disease

Righ hypochondrial pain

abdominal distention

fluid retention

Haematemesis

Breast swelling

# data[].attributes.body
Jaundice (icterus) is detectable clinically when the serum bilirubin is >50 μmol/L (3 mg/dL).

# data[].attributes.body
Can be divided into types:

1. Hemolytic jaundice - due to breakdown of red cells bilirubin production is increased

1. Causes elevated unconjugated bilirubin (because heme, that is produced when RBC breakdown, is needed to make unconjugated bilirubin)

2. No bilirubin in urine

2. Congenital - defects in conjugation or hepatic uptake of bilirubin (Gilbert’s syndrome, Crigler-Najjar syndrome)

1. Causes elevated conjugated and unconjugated bilirubin

2. No bilirubin in urine

3. Gilbert’s syndrome → UDP glucuronyl transferase

3. Cholestatic - duct obstruction (extrahepatic) or failure of bile secretion (intrahepatic)

1. Causes elevated conjugated bilirubin

2. Bilirubin in urine (makes sense because only conjugated bilirubin can be excreted into the urine). Shows you that bilirubin is being formed but can’t be transported into the bile as it should be.

# data[].attributes.body
duct obstruction

# data[].attributes.body
some kind of failure inside the liver

# data[].attributes.body
The accumulation of fluid in the peritoneal cavity, causing abdominal swelling.

# data[].attributes.body
- Due to portal hypertension
- Due to Na/H2O retention. More fluid is retained
- Low serum albumin due to liver function being impaired
-

# data[].attributes.body
Alcohol
Hepatitis
Non alcoholic fatty liver disease
Acute liver injury

# data[].attributes.body
Chronic injury to the liver in inflammation, necrosis, eventually fibrosis.

Fibrosis is initiated by activation of the stellate cells. Stellate cells are activated by many cytokines and their receptors, reactive oxygen intermediates, and other paracrine and autocrine signals.

Stellate cells become swollen and there is upregulation of cytokines, TGFbeta

The characteristic features of cirrhosis are regenerating nodules separated by fibrous septa and loss of the normal lobular architecture within the nodules.

The cell death and cirrhosis will cause the liver to shrink.

# data[].attributes.body
Liver function

albumin and prothrombin time

Biochemistry (raise in ALP)

AST & ALT --> indicate liver damage. AST is the least specific one (also seen in cardiac failure)

ALP

Viral markers

Hyponatraemia

Imaging: ultrasound, CT, endoscopy

Biopsy

# data[].attributes.headline
Excess fat buildup in the liver (with or without alcohol as a cause)

# data[].attributes.subject
Excess fat buildup in the liver (with or without alcohol as a cause)

# data[].attributes.body
Insulin resistance

leads to high levels of glucose. Due to changed metabolism, there is an increase in NADH. This leads to increased fatty acid synthesis

Increase in fat storage & fatty acid oxidation process

Steatosis

Steatohepatitis

# data[].attributes.body
This is a form of chronic liver disease associated with the metabolic syndrome. NAFLD refers to the presence of hepatic steatosis, with or without inflammation and fibrosis, when no other causes of secondary hepatic fat accumulation (e.g., heavy alcohol consumption) are present.

NAFLD is strongly associated with metabolic risk factors such as obesity, dyslipidemia, insulin resistance, and type 2 diabetes mellitus

# data[].attributes.body
Ethanol is metabolized by the liver. The pathways this happens through, can lead to hepatic accumulation of fatty acid.

Genetic predisposition is recognized

Pathology:

Fatty change

o   The metabolism of alcohol produces fat in the liver

o   This is minimal with small amount of alcohol, but with larger amounts the cells become swollen with fat (steatosis)

o   No liver cell damage, fat disappears on stopping alcohol

Alcoholic hepatitis

o   Infiltration by leucocytes and hepatocyte necrosis

Alcoholic cirrhosis

# data[].attributes.body
Imaging
- changed echogenicity
Biopsy
ALT & AST increased

# data[].attributes.body
active lifestyle
Stop drinking

# data[].attributes.body
HAV is most commonly seen.
HDV is a RNA virus that requires HBD to cause infection

# data[].attributes.body
Toxic Hepatitis: Most cases of drug-induced liver injury present as acute hepatitis
Alcoholic Hepatitis: Alcohol consumption is the major cause of the burden of liver disease in Western countries

# data[].attributes.body
The viruses infect the human body by different means of transmission. The Hepatitis viruses have special affinity for liver cells. The viruses infect the hepatocytes. They multiply inside the hepatocyte. Due to this, the antigen structure on the hepatocytes change. This is recognized as foreign and starts to destroy these hepatocytes by self-mediated immune damage. This leads to apoptosis, necrosis & fibrosis.

# data[].attributes.body
Prodromal phase

symptoms due to viraemia (flu like symptoms)

Icteric phase

Due to liver damage

jaundice

dark urine

hepatomegaly

increased AST & ALT

Convalescent phase

recovery phase

symptoms gradually improve

HBV & HCV have potential to become chronic

# data[].attributes.body
Liver biochemistry & viral markers

# data[].attributes.body
Hepatitis usually has spontaneous resolution (HAV & HEV).

# data[].attributes.body
1. increased risk massive GI bleeding
2. Malabsorption of fat
3. Hepatocellular carcinoma
4. Pulmonary complications:

Hepatopulmonary syndrome

Portopulmonary syndrome

Hepatic hydrothorax

5. Portal hypertension
because of fibrosis/scarring, there is more resistance to blood flow. The pressure within the liver increases and therefore there is increased portal blood flow. This contributes to ascites and splenomegaly
6. Altered consciousness due to liver disease. The toxics do not get filtered anymore, so they enter the brain

# data[].attributes.body
A mild liver disorder in which the liver does not properly process bilirubin. Many people never have symptoms. Occasionally a slight yellowish color of the skin or whites of the eyes may occur.

# data[].attributes.body
Bilirubin is insoluble. It needs to be binded to Albumin to transport = unconjugated. This can not be present in bile and not be excreted in urine.

When it is in the liver bilirubin is conjugated to glucaronic acid and can then be binded to bile

# data[].attributes.body
Cholangitis = inflammation of the bile ducts
- most common in middle aged females
- autoimmune conditions which causes obstruction of intrahepatic bile ducts
- leads to scarring

Investigations:
- antibodies
- elevated ALP & bilirubin

Prevalence = 240/1.000.000

# data[].attributes.body
Fibrosing destruction of intra- and extrahepatic bile ducts. Associated with Destructive cholitis.

Usually Asymptomatic (detected by change)

Symptoms: Jaundice

Treatment: transplantation

# data[].attributes.body
Cirrhosis
Persistent symptoms
Severe chronic hepatitis
Only if patients stopped drinking (6 months)

# data[].attributes.body
90% 1 year
70-85% 5 year survival