Lecture 24 Flashcards
What are some structures of the hepatobiliary system?
Common bile duct, pancreatic duct, ampulla of vater (hepatopancreatic ampulla), sphincter of oddi
How is the liver connected to the digestive tract?
Two links: portal vein and bile duct
Congestive Heart Failure
- Valves are not present in the inferior vena cava and hepatic veins
- Increase in central venous pressure causes and enlargement of the liver (blood engorgement)
Portal Hypertension
- Obstruction to blood flow in the liver during cirrhosis, together with failure of the hepatocytes to produce plasma proteins (albumin) results in portal hypertension
- Portal hypertension increases the hydrostatic pressure in the portal vein and its intrahepatic branches and fluid accumulates in the peritoneal cavity (ascites)
- Loss of fluid is aggravated by reduced plasma oncotic pressure due to reduction in plasma albumin
- Cirrhosis may develop following chronic hepatitis or alcoholic liver disease
- Splenomegaly
Carcinoma of the Pancreas
Carcinoma of the head of the pancreas (60% of pancreatic tumors) obstructs by compression the outflow of bile through the ampullary region
Explain the structure of the liver.
- Encapsulated, self-contained organ that is loosely attached to adjacent organs
- Largest gland of the human body
- Four poorly defined lobes
- Surrounded by collagen-elastic fiber-containing capsule (of Glisson) and is lined by the peritoneum
What tract is the liver part of and how is it connected?
- Digestive tract
- Connected by the portal veins and biles ducts
What happens with an obstruction of bile ducts?
Jaundice caused by hyperbilirubinemia
Explain the functions of the liver.
- Essential for uptake, processing, and excretion of bilirubin released from aged RBCs (Hyperbilirubinemia)
- Major source of plasma proteins (except immunoglobulins (albumin, coagulation factors))
- Rich in enzymes (released into circulation upon liver injury)
- Removes from circulation, metabolizes, and detoxifies or modifies many drugs, hormones, cytokines
- Certain viruses have exclusive tropism for liver
- Toxic dump
What is a distinct feature of liver cells?
They can regenerate
How is the liver involved in cancer?
It can give rise to tumors, but it is even more often involved by tumor metastases (Hepatocellular carcinoma (Hepatitis B))
What are the causes of liver failure?
Hepatitis (viral and non-viral), cirrhosis, liver cancer
What are the two conditions that occur in liver failure?
Hepatorenal syndrome, hepatic encephalopathy
Zone 1 of the hepatic acinus
- Closer to arterial center
- Highest oxygen saturation, nutrients levels, and metabolic activity
- Hepatocytes here are the first to begin the regenerative process after a partial hepatectomy
- They are also the first to get hit if exposed to a direct toxicant (ex: phosphorus)
Zone 3 of the hepatic acinus
- Most susceptible to ischemia and is the first to undergo necrosis in systemic hypoxia
- Indirect toxicant (ex: substances that become toxic only after being metabolized) mostly damage zone 3 (ex: carbon tetrachloride)
Bile Lakes
Formed by bile killing perivenular cells (zone 3)
What are the three cell types seen in the sinusoid-lining?
- Epithelial cells with thin fenestrated cytoplasm
- Large plump phagocytic cells (Kupffer cells)
- Stellate cells, perisinusoidal cells of Ito, or hepatic lipocytes
Kupffer cells
Large, plump phagocytic cells which are part of monocyte-macrophage defense system and with spleen (participate in removal of spent erythrocytes and other particulate debris from circulation)
Stellate cells
- Aka perisinusoidal cells of Ito or hepatic lipocytes
- Cannot be easily distinguished by light microscopy
- Dual functions: vitamin A storage and production of extracellular matrix and collagen
Space of Disse
Chylomicron remnants (lipoproteins) get processed and cirrhotic changes occur
The liver cell is __________ and has an ________ side, containing the _________________, and a basolateral domain, which abuts the _____________.
Polarized; apical side; biliary canaliculus; sinusoids
What is the function of the sublingual administration?
Venous return from the buccal cavity
What is the function of the rectal administration?
Venous return from the rectum
What does the biochemical properties of a drug determine?
The optimal route of administration
What does the optimal absorption of weak acids/bases depend on?
pH of the GI tract or surrounding environment
What can impact the absorption of drugs?
GI disease
First-pass effect
- Major mechanism that determines the ultimate concentration of a drug in the plasma
- Refers to the combined effect of metabolism by the liver and in the gut
Explain the process of drug absorption for drugs absorbed beyond the oral cavity.
Transported to the liver via the portal vein, where most drugs are metabolized to less active metabolites
Drugs administered sublingually and rectally…
avoid first-pass metabolism in the liver
Does the lymphatic system follow first pass metabolism?
No
When should oral drugs be avoided?
- If the drug causes nausea and vomiting
- If the patient is currently vomiting
- If the patient is unwilling or unable to swallow (child, mentally retarded, unconscious)
- If the drug is destroyed by digestive enzymes (insulin)
- If the drug is not absorbed through the gastric mucosa (aminoglycosides)
- If the drug is rapidly degraded (lidocaine)
