10/20- Review of Liver Histology, Physiology, and Disease Presentation Flashcards
What are the major functions of the liver?
- Maintains metabolic homeostasis by integrating carbohydrate, lipid, and protein metabolism
- Supplies massive amounts of energy
- Exocrine gland: source of bile salts for fat absorption, including fat-soluble Vitamins A, D, K, E
- Endocrine gland: hydroxylation of Vitamin D
- Biosynthesis of most plasma proteins, albumin, lipoproteins, transferrin, Vitamin K-dependent clotting factors, other coagulation proteins such as protein S and protein C
- Hepatic biotransformation: converts hydrophobic substances to water-soluble products which excreted in bile or urine
- Detoxification of lipid-soluble endogenous waste products and xenobiotic pollutants -> excretion into bile
- Clears and metabolizes bacterial products from gut (e.g. ammonia, endotoxins)
- Phagocytosis of particulate matter by reticuloendothelial cells (e.g. Ag-Ab complexes, bacteria)
- Reservoir in blood volume regulation
What are the different cell types of the liver?
- Hepatocytes (60-65% total number, 90% total mass)
- Kupffer cells (10%)
- Sinusoidal endothelial cells (16%)
- Hepatocyte stellate cells (Parasinusoidal or Ito cells)
- Biliary epithelial cells
- Canals of Hering
- Ductules (cholangioles)
- Fibroblasts
- Stem cells
Describe the circulation of the liver
- Gets 1/4 of the CO (1.5 L/min)
- 30-45% of hepatic blood flow is arterial while most (60-70%) is portal venous
- Arterial flow is higher pressure (99 mmHg) and more oxygenated (18 mL/dL)
- Portal venous flow is lower pressure (5-10mmHg, 14 mL/dL)
- Central venous pressure is 2-3 mmHg
- Enterohepatic circulation
Describe lymph flow and the liver
- 0.5-1L/day of lymph
- Largest single source of lymphatic flow at any given time (15-20% of body total)
What is enterohepatic circulation?
- Bile salts and some urobilinogen reabsorbed from ileum and colon into portal circulation
- Re-excreted by liver, 15-30 g/day
Describe structure of hepatic lobules
Need more…
- Endothelial cells but no tight junctions
- Sinusoidal space with Kuppfer cells
- Space of Disse
Describe structure of acinus of Rappaport
- Hepatic a and portal vein with bile duct on periphery - Zone 1 is closest to blood supply
- Zone 3 is closer to terminal hepatic vein in the center of the acinus
Describe flow of bile and blood through the acinus
- Portal triad on periphery; blood flow moves from zone 1 ->3 toward periphery and central vein
- Bile flows inside -> out via the bile ductule to the bile duct and portal triad
What are clinical presentations of acute liver disease?
- Asymptomatic
- Malaise, fatigue
- Nausea, vomiting, anorexia
- Fever
- Localized tenderness
- Scleral icterus, jaundice
- Dark urine, pale stools
- Bleeding
- Seizures, coma
- Hepatic encephalopathy
- Renal failure
What are clinical presentations of chronic liver disease?
- Any symptoms or signs of acute liver disease
- Bleeding or thrombotic complications
- Small firm liver (cirrhosis) or hepatomegaly (fat or tumor infiltration)
- Splenomegaly
- Ascites
- Spontaneous bacterial peritonitis
- Abdominal collateral vessels
- Esophageal and gastric varices
- Spider angiomata on palms
- Gynecomastia
- Testicular atrophy
- Decreased libido
- Pruritus
- Xanthomas
- Glucose intolerance
- Amino aciduria
- Vitamin deficiencies
- GI: ulcers, diarrhea, steatorrhea
- Anemia: Iron and folate deficiency
- Muscle wasting, secondary to impaired protein synthesis
What are the patterns of liver injury?
- Necrosis
- Degeneration
- Inflammation
- Regeneration
- Fibrosis
- Kupffer cell hyperplasia, hypertrophy
- Cholestasis
- Steatosis
In liver injury, what are the different variations as to the extent of necrosis?
- Associated conditions
- Focal Apoptosis: programmed cell death
- Hepatocytolysis: lytic necrosis, hepatocytes swell and rupture
- Zonal: region of lobule, e.g. zone 3
- Submassive: entire lobules
- Massive: most of liver
- Bridging: links 2 adjacent structures
- Interface hepatitis: piecemeal necrosis along limiting plate
What is seen here?
Apoptosis
- Programmed cell death
What is seen here?
Hepatocytolysis
- Lytic necrosis
- Hepatocytes swell and rupture
What is seen here?
Interface hepatitis
- Piecemeal necrosis along limiting plate
What is seen here?
Zonal necrosis
- Necrosis of a region of lobule, here zone 3
- Can happen if someone is severely hypotensive (e.g. after surgery)
What is seen here?
Submassive necrosis
- Entire lobules
What is seen here?
Massive necrosis - Most of liver
What are the different patterns of livery injury in terms of degeneration?
Degeneration = step short of necrosis
- Ballooning
- Feathery
What is ballooning degeneration
- Caused by
- Cellular swelling with damage
- Damage from toxic or immunologic insults, e.g. acute viral hepatitis, steatohepatitis
What is feathery degeneration?
- Caused by
- Chronic cholestasis
- Diffuse foamy appearance of swollen hepatocytes
What are the different types of liver injury in terms of inflammation?
- Chronic
- Acute
- Granulomatous
Describe regeneration following liver injury
- Hepatocytes can proliferate in response to resection or cell death
- Proliferation quiescent under normal conditions
- Regenerative capacity of mature hepatocytes is demonstrated after partial hepatectomy
- Regeneration occurs in all but the most fulminant hepatic diseases
- Bile ductules serve as reserve for restitution of severe injury
- Possible role of stem cells
- 2-4 stem cells identified in donor liver per 30K-50K hepatocytes
Abnormal regeneration of liver may cause what?
Fibrosis/cirrhosis
What is cholestasis?
Impairment of bile flow and failure to secrete constituents of bile
- Bile is the primary path for eliminating bilirubin, excess cholesterol (free and bile salts), and xenobiotics which are not water soluble
- Thus, there is retention in blood of all elements of bile (bilirubin, bile salts, cholesterol…)
- Cholestasis does NOT = conjugated hyperbilirubinemia
What are the main categories of cholestasis causes?
- Intrahepatic
- Large duct obstruction
Specifics of cholestasis etiology:
- Intrahepatic
- Large duct obstruction
Intrahepatic
- Hepatocellular dysfunction
- Hepatitis
- Drugs
- Obstruction: small ducts
- Cirrhosis
- Primary biliary cirrhosis
Large duct obstruction
- Extrahepatic bile duct
- CBD stricture
- Stones
- Flukes
- Cancer
- Large intrahepatic duct
Presentation of cholestasis due to intrahepatic vs. large duct obstruction?
- Overlap in morphologic changes between diseases with bile duct obstruction and those in which cholestasis purely hepatocellular in origin
- Features of nonobstructive cholestasis also seen in obstructive cholestasis
- Pathologists look for additional obstructive changes to support large duct obstruction
- Large duct obstruction and other etiologies of cholestasis can also result in seeing canalicular and intracellular cholestasis
What are histological features of large duct obstruction causing cholestasis?
- Neutrophils in interlobular bile ducts
- Portal edema and ductular reaction
- Bile plugs in interlobular bile ducts
- Bile lakes and infarcts
What are histological features of large duct obstruction causing chronic cholestasis?
- Bile plugs in ducts and ductules
- Ductal and ductular proliferation
- Portal fibrosis
Chronic cholestasis can result in what changes (any etiology)?
- Feathery degeneration
- Copper storage, periportal. Not all increased copper is Wilson’s disease
- Mallory-Denk bodies (Mallory hyaline): not restricted to alcoholic liver disease
- May or may not see increased bile pigment
What is Steatosis? - Types - Subtypes
Accumulation of TG fat droplets in hepatocytes
- Macrovascular
- Large droplet type, single large droplet of fat that displaces nucleus
- Small droplet type
- Microvascular
- Multiple small droplets that don’t displace the hepatocyte nucleus
T/F: The normal liver stores fat
False
Describe lipid biosynthesis in normal liver
The liver:
- Maintains cell membranes
- Supports hepatic bile secretion
- Key factor in assembly of VLDL which exported from liver into circulation
