10/20- Review of Liver Histology, Physiology, and Disease Presentation Flashcards
1
Q
What are the major functions of the liver?
A
- 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
2
Q
What are the different cell types of the liver?
A
- 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
3
Q
Describe the circulation of the liver
A
- 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
4
Q
Describe lymph flow and the liver
A
- 0.5-1L/day of lymph
- Largest single source of lymphatic flow at any given time (15-20% of body total)
5
Q
What is enterohepatic circulation?
A
- Bile salts and some urobilinogen reabsorbed from ileum and colon into portal circulation
- Re-excreted by liver, 15-30 g/day
6
Q
Describe structure of hepatic lobules
A
Need more…
- Endothelial cells but no tight junctions
- Sinusoidal space with Kuppfer cells
- Space of Disse
7
Q
Describe structure of acinus of Rappaport
A
- 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
8
Q
Describe flow of bile and blood through the acinus
A
- 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
9
Q
What are clinical presentations of acute liver disease?
A
- Asymptomatic
- Malaise, fatigue
- Nausea, vomiting, anorexia
- Fever
- Localized tenderness
- Scleral icterus, jaundice
- Dark urine, pale stools
- Bleeding
- Seizures, coma
- Hepatic encephalopathy
- Renal failure
10
Q
What are clinical presentations of chronic liver disease?
A
- 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
11
Q
What are the patterns of liver injury?
A
- Necrosis
- Degeneration
- Inflammation
- Regeneration
- Fibrosis
- Kupffer cell hyperplasia, hypertrophy
- Cholestasis
- Steatosis
12
Q
In liver injury, what are the different variations as to the extent of necrosis?
- Associated conditions
A
- 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
13
Q
What is seen here?
A
Apoptosis
- Programmed cell death
14
Q
What is seen here?
A
Hepatocytolysis
- Lytic necrosis
- Hepatocytes swell and rupture
15
Q
What is seen here?
A
Interface hepatitis
- Piecemeal necrosis along limiting plate
16
Q
What is seen here?
A
Zonal necrosis
- Necrosis of a region of lobule, here zone 3
- Can happen if someone is severely hypotensive (e.g. after surgery)
17
Q
What is seen here?
A
Submassive necrosis
- Entire lobules
18
Q
What is seen here?
A
Massive necrosis - Most of liver
20
Q
What is ballooning degeneration
- Caused by
A
- Cellular swelling with damage
- Damage from toxic or immunologic insults, e.g. acute viral hepatitis, steatohepatitis
21
Q
What is feathery degeneration?
- Caused by
A
- Chronic cholestasis
- Diffuse foamy appearance of swollen hepatocytes
28
Q
Presentation of cholestasis due to intrahepatic vs. large duct obstruction?
A
- 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
29
Q
What are histological features of large duct obstruction causing cholestasis?
A
- Neutrophils in interlobular bile ducts
- Portal edema and ductular reaction
- Bile plugs in interlobular bile ducts
- Bile lakes and infarcts
30
Q
What are histological features of large duct obstruction causing chronic cholestasis?
A
- Bile plugs in ducts and ductules
- Ductal and ductular proliferation
- Portal fibrosis
32
Q
What is Steatosis? - Types - Subtypes
A
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
