The liver is a wedge-shaped organ that is located underneath the diaphragm in the right upper abdominal quadrant. It is covered by a capsule and connected to surrounding structures via ligaments. The structures are found in a fissure between two of the four liver lobes. The and the provide the liver with a dual blood supply. Microscopically, the liver is divided into lobules, each with a central vein and a . Each portal triad consists of an artery, vein, and bile ductule, and is accompanied by lymphatic vessels and a branch of the vagus nerve. Liver parenchyma consists of hepatocytes and hepatic sinusoids. Hepatic sinusoids drain into the central vein of each lobule. The liver is responsible for energy metabolism, synthesis of various substances (e.g., glucose, ketones, bile acid), glucose homeostasis regulation, nutrient storage, and the clearance/excretion of toxins (e.g., ethanol) and waste products. In fetuses, the liver is the site of erythropoiesis from 6 weeks' gestation until birth. During embryogenesis, the liver originates from the endoderm. The ligamentum teres forms from the obliterated umbilical vein and is located in the free edge of the falciform ligament.
- Largest gland in the body
- Weight: ∼ 1.2–1.5 kg in adults (2.6–3.3 pounds) 
- Consists of four lobes:
- Right (largest)
- Typically divided into 8 segments
- Surrounded by the hepatic capsule (two layers)
- Porta hepatis structures
- Location: under the diaphragm in the right upper abdomen.
- Connects liver to abdominal wall
- Divides liver into right (larger) and left (smaller) lobes
|Vasculature of the liver|
|Type of vessel||Vessels|
- Visceral peritoneum: serosa that covers the liver
- Lobules: Sheets of connective tissue divide the liver into small hexagonal units called lobules. These consist of:
- Mostly consists of hepatocytes
- Contain large amounts of smooth endoplasmic reticulum, which is involved in detoxification
- The basolateral surface of hepatocytes faces the sinusoids. .
- The apical surface of hepatocytes faces the lumen of the bile canaliculi.
- Hepatic sinusoids; are large capillaries lined with highly fenestrated endothelial cells: Blood flows through the sinusoids and empties into the central vein of each lobule.
- Mostly consists of hepatocytes
- Absorption of nutrients from blood and secretion of products synthesized by special carriers into the blood
- Kupffer cells (a type of macrophage) are housed in the sinusoids. These cells phagocytize foreign particles, bacteria, and damaged, old blood cells.
- The plasma-filled space between the sinusoids and hepatocytes is called the perisinusoidal space (of Disse): contains hepatic stellate cells (Ito cells), which store vitamin A and are the main source of extracellular matrix production in liver injury (formation of scar tissue → fibrosis)
- Zone I: The periportal zone
- Zone II: intermediate zone (affected in )
- Zone III: pericentral vein/centrilobular zone
Zone I is first and zone III is last to receive O2.
Zone II is affected in yellow fever.
|Functions of the liver|
|Function||Related biochemical pathways|
|Energy metabolism|| |
|Detoxification and clearance/excretion|| |
Breakdown of ethanol
Oxidation of ethanol to acetaldehyde by alcohol dehydrogenase
- Fomepizole competitively inhibits alcohol dehydrogenase; used in the treatment of methanol and ethylene glycol poisoning to prevent the formation of toxic metabolites 
- Alternatively, ethanol can be given, as it will compete for alcohol dehydrogenase and thereby limit the formation of formaldehyde.
Oxidation of acetaldehyde to acetate by acetaldehyde dehydrogenase
- Disulfiram competitively inhibits acetaldehyde dehydrogenase, which is useful in the treatment of alcohol use disorder: Acetaldehyde builds up quickly after alcohol consumption and causes hangover symptoms, which usually discourages patients from drinking. 
- Other drugs (e.g., metronidazole) have a disulfiram-like effect, which is why the concomitant use of alcohol and antibiotics is not recommended.
- Ligation of acetate and coenzyme A to acetyl-CoA by thiokinase under ATP consumption
When large quantities of alcohol are consumed, acetaldehyde builds up faster than it can be metabolized by acetaldehyde dehydrogenase. Excess acetaldehyde plays a major role in hangover symptoms.
FOMEpizole: For Overdosing on Methanol or Ethylene glycol!
Metabolic consequences of heavy ethanol consumption
- Anion gap metabolic acidosis
- Fasting hypoglycemia
Fasting and starvation
- The main purpose of all the metabolic alterations during fasting and starvation is to provide energy to supply vital organs (e.g., the brain) and cells (especially the RBCs) to guarantee their function and protein preservation
- The metabolic processes during fasting and starvation are primarily regulated by
- The amount of stored substrate (e.g., adipose tissue) determines the survival time.
|Energy sources during fasting and starvation|
|Time||Biochemical reactions and substrates|
|Fasting (in between meals)|
|Starvation days 1–3|| |
|Starvation after day 3|| |
- Hepatic infection
- Hepatic tumors
- Hereditary diseases