Pathology - S2B3 - Liver 1

Front 1

Explain how the Liver is attached to the GI tract

Back 1

-Liver is connected to the Duodenum by the extrahepatic bile ducts
-Hepatic ducts drain the bile from the liver, forming the Common Bile Duct
-Common Bile Duct is laterally attached to the Gall Bladder by the Cystic Duct
-terminal portion of the Common Bile Duct passes thru the head of the pancreas & prior to entering the duodenum is confluent with the Main Pancreatic Duct at the Papilla of Vater

Front 2

Describe the blood supply of the Liver

Back 2

Liver had DUAL blood supply
-2/3 arrives from the Portal Vein
-1/3 arrives from the Hepatic Artery

Front 3

Describe how blood flows through the liver

Back 3

1. Portal Vein and Hepatic Artery form several branches which terminate in the Portal Tracts
2. Portal Vein & Hepatic Artery empty blood into Sinusoids of the Hepatic Acinus
3. Sinusoidal blood drains into the Terminal Hepatic Venule
4. Terminal Hepatic Venule -> Hepatic Vein -> IVC

Front 4

What comprises the Portal Tract?

Back 4

1. Bile Ducts

2. Portal Vein

3. Hepatic Artery

Front 5

Describe the Sinusoids of the Liver

Back 5

-Modified capillaries that form the vascular spaces of the Acinus
-Fenestrated Endothelial Cells = lined with a discontinuous basement membrane that separates the lumen from the perisinusoidal Space of Disse

Front 6

Describe Kupffer Cells

Back 6

-fixed Macrophages located in the spaces of Disse
-phagocytic & participate in the uptake of particulate material from circulation (ie - take up fragments of destroyed RBC's in hemolytic anemia)

Front 7

Describe liver Stellate Cells (Ito cells or Lipocytes)

Back 7

Fat-storing mesenchymal cells known to be an important storage site for Vitamin A
-in Cirrhosis they transform into collagen-producing myofibroblasts

Front 8

Left = Portal Tract

Right = Terminal Hepatic Venule (Central Vein)

Back 8

What is shown at the left?

Right?

Front 9

What is the "Limiting Plate"?

Back 9

Interface between the connective tissue of the Portal Tracts and the periportal Hepatocytes

Front 10

Describe Bile Canaliculi

Back 10

Bile-filled narrow spaces formed between adjacent hepatocytes

Front 11

Fill in the blanks

Back 11

-

Front 12

What % of Cardiac Output does the Liver receive?

Back 12

25%

*Hepatic Artery brings in 30-40% of blood
*Portal Vein brings in 60-70%

Front 13

Describe the "Hepatic Lobule"

Back 13

Liver cells are arranged around the Terminal Hepatic Venule (Central Vein)

Front 14

Describe the "Hepatic Acinus"

Back 14

Portal Tracts are the centers of the functional hepatic units
-blood enters into the center of the unit & flows toward the periphery to finally reach the THV

Front 15

Describe what happens in Cholestasis

Back 15

Bile Canaliculi become dilated

Front 16

Discuss the Metabolic functions of the Liver

Back 16

Hepatocytes process almost all nutrients entering the body thru the GI tract
-Carbohydrate, Amino acid, & fat metabolism

Front 17

Discuss the Secretory function of the Liver

Back 17

Synthesizes almost all blood plasma proteins, lipoproteins, and glycoproteins

Front 18

Discuss the Storage function of the Liver

Back 18

-Store energy and metabolites, predominately in the form of lipids and carbohydrates
-Store Vitamins (folic acid, B12, vitamin A), Oligominerals (Copper & Iron)

Front 19

Discuss the Excretory function of the Liver

Back 19

Excretes Bile, Bilirubin, & lipids (cholesterol) into the GI tract

Front 20

Which LFT's are used to assess the Hepatic Secretory function?

Back 20

1. Serum Albumin = synthesized constantly & has half-life of ~ 3 wks = takes time to develop Hypoalbuminemia

2. Coagulation proteins = use Prothrombin Time (PT) to assess liver fxn loss

Front 21

Which LFT's are used to assess the Excretory functions of the Liver?

Back 21

1. Bilirubin = conjugated bilirubin that cannot be excreted into the Intestine accumulates in the blood and can be measured as Direct Bilirubin

2. Alkaline Phosphatase = found along the liver cell membrane lining the intercellular canaliculi

3. Gamma-glutamyl transpeptidase = primarily a hepatic enzyme (vs. Alk Phos) = marker of liver cell injury (esp. alcohol-induced injury)

Front 22

What are elevated levels of Alkaline Phosphatase typical of?

Back 22

Obstructive Jaundice

*Alk Phos is found along the liver cell membrane lining the Intercellular Canaliculi

Front 23

What lab tests are used to assess Liver Cell injury?

Back 23

1. Aspartate Amino-transferase (AST)

2. Alanine Amino-transferase (ALT)

**cytoplasmic enzymes released into circulation upon liver cell injury
**not liver specific but liver is major source of these plasma enzymes

Front 24

What are the 3 most common causes of Fatty Liver?

Back 24

1. Obesity
2. Diabetes
3. Alcohol

Front 25

List some reversible changes that occur in Liver injury

Back 25

1. Hydropic change
2. Ballooning & feathery degeneration

Front 26

What is glycogen accumulation in the Liver most commonly due to?

Back 26

Diabetes

Front 27

What would cause Hemosiderin accumulation in the Liver?

Back 27

Hemochromatosis

Multiple blood transfusions

Front 28

What is Centrolobular Necrosis?

Back 28

necrosis in Zone 3 = part furthest away from Portal Tract but close to the Terminal Hepatic Venule = last part to receive blood

Front 29

Macrovesicular Fatty Liver
-Fatty change due to Chronic Alcoholism
-Mallory Hyaline is also present

Back 29

What is seen here?

Front 30

Alcohol-induced hepatitis
-fatty change
-focal liver cell necrosis
-infiltrates of neutrophils
-Mallory Hyaline

Back 30

What is seen here?

Front 31

Viral Hepatitis
-Apoptotic cells = Councilman bodies
-Lymphocyte infiltration

Back 31

What is seen here?

Front 32

Viral Hepatitis
-Vacuolar degeneration
-Councilman body
-inflammatory lymphocytes

Back 32

What is seen here?

Front 33

List the signs & symptoms of Liver Disease

Back 33

Constitutional (nonspecific)
1. Anorexia
2. Nausea
3. Weight loss

Jaundice
-dark urine
-Acholic (pale) stools

Bleeding
-hematemesis (blood in vomit)
-Hematochezia (blood in stool)

Hormonal problems
-amenorrhea, gynecomastia, impotence, spider nevi, palmar erythema

Front 34

What are the 3 possible signs of Portal HTN?

Back 34

1. Esophageal varices

2. Hemorrhoids

3. Caput Medusa

Front 35

What are the 3 consequences of Portal Hypertension

Back 35

1. Ascites = accumulation of serous fluid in abdominal cavity

2. Generalized edema = Anasarca

3. Hemorrhoids, Caput Medusa, Esophageal Varices

Front 36

Discuss the Pathogenesis of Ascites in Cirrhosis

Back 36

1. Portal HTN = increased hydrostatic pressure leads to transudation of fluid into abdominal cavity

2. Hypoalbuminemia = liver cannot produce adequate albumin

3. Lymphatic Overflow

4. Hyperaldosteronism = aldosterone is released in response to volume regulatory sensors = conserves Na+ & H2O = water overflows into abdominal cavity

Front 37

What are the signs & symptoms of Biliary disease?

Back 37

1. Subcostal & RUQ pain

2. Biliary colic & fever

3. Jaundice

4. Murphy sign = tender gallbladder on taking deep breath

5. Courvoisier sign = palpable distended gallbladder

Front 38

What are the 3 forms of Jaundice?

Back 38

1. Hemolytic

2. Hepatocellular

3. Obstructive

Front 39

Define Jaundice

Back 39

yellow discoloration of the skin, sclera (icterus) & mucous membranes due to increased levels of BILIRUBIN in circulation

Front 40

Describe how Bilirubin is formed

Back 40

1. release of Heme from RBC
2. Heme -> Biliverdin -> Bilirubin (macrophage in spleen & liver)
3. Bilirubin is bound to Albumin = Unconjugated or Indirect Bilirubin
4. Conjugation of Bilirubin to Glucuronic Acid by UGT in Hepatocytes
5. Excretion of water-soluble Bilirubin Glucuronides = Conjugated or Direct Bilirubin
6. Deconjugation of some Direct Bilirubin by intestinal bacteria to Urobilinogen = 80% is excreted in feces together with Conjugated Bilirubin
7. Recirculation of Urobilinogen in Enterohepatic cycle; small amount is excreted in urine

Front 41

What enzyme performs Bilirubin conjugation?

Back 41

Uridine Diphosphate-Glucuronosyl Transferase (UGT1A1)

Front 42

What 2 things would cause increased production of Bilirubin?

Back 42

1. Hemolysis

2. Hematomas

Front 43

What syndrome has reduced hepatic uptake of Bilirubin?

Back 43

Gilbert Syndrome

Front 44

What conditions have reduced conjugation of Bilirubin resulting in Jaundice?

Back 44

1. Physiologic in Neonates
2. Gilbert Syndrome (some)
3. Crigler-Najjar Syndrome (deficiency of Glucuronosyl Transferase)
4. Hepatitis (viral or drug-induced)

Front 45

What conditions have reduced excretion of Bilirubin leading to Jaundice?

Back 45

1. Dubin-Johnson syndrome
2. Rotor syndrome
3. Hepatitis (viral or drug-induced)

**result in Conjugated Hyperbilirubinemia

Front 46

List 6 causes of Extrahepatic Bile Duct Obstruction resulting in Jaundice

Back 46

1. Gallstones
2. Tumors of the Common Bile Duct, Ampulla of Vater, Head of pancreas
3. Primary Sclerosing Cholangitis
4. Strictures due to Surgery
5. Congenital Atresia
5. Parasites = Liver flukes, Ascaris

Front 47

Define Cholestasis

Back 47

condition where Bile cannot flow from the Liver to the Duodenum

Front 48

What are the signs & symptoms of Cholestasis?

Back 48

1. Jaundice due to Conjugated Bilirubin
2. Pruritis = due to bile acids circulating in the blood
3. Xanthomas = due to cholesterol that is normally excreted in Bile, are taken up by Macrophages
4. Acholic stools (pale stools) = due to absence of bile excretion
5. Dark urine = due to Bilirubin
6. Malabsorption, steatorrhea, Vitamin deficiency (DAKE vitamins)

Front 49

What lab findings are consistent with Cholestasis?

Back 49

1. increased CONJUGATED Bilirutin

2. increased Alkaline PHosphatase

3. increased GGT

Front 50

What are the liver biopsy findings consistent with Obstructive Jaundice?

Back 50

1. Bile plugs in Intercellular Canaliculi
2. Bile accumulation in Liver cells -> feathery degenaration -> Bile lakes -> Bile infarcts
3. Uptake of bile by Kupffer cells
4. Bile duct proliferation
5. Portal fibrosis -> Portal-Portal bridging fibrosis -> biliary cirrhosis

Front 51

Obstructive Jaundice
-bile is present in Intercellular Canaliculi

Back 51

What is this showing?