Liver Pathology I - SRS Flashcards
1
Q
What enters the liver at the porta hepatis?
A
- Portal vein
- hepatic artery
- bile duct
2
Q
Identify the structures shown.
A
3
Q
What is the normal diameter of an anatomic liver lobule?
A
1-2 mm
4
Q
Identify the indicated structures
A
5
Q
What is the space of Disse?
Obstruction here can lead to what?
A
Space between Sinusoids and the hepatocytes.
Contains lymph and interstitial fluid.
Can lead to portal HTN
6
Q
Identify the blanked out structures
A
Top: hepatocyte
Bottom: Bile canaliculi
7
Q
Identify
A
Left: Lumen of the sinusoid
Right: space of disse
8
Q
The endothelial layer is fenestrated and not supported by a basal lamina. What are the hepatocytes directly exposed to?
A
Plasma
9
Q
Where are we here?
A
Lumen of a hepatic sinusoid with the endothelial cell coating, displaying the typical fenestrations arranged as clusters and forming the so-called sieve plates.
10
Q
What cells are found in the cords and sinusoids?
A
Hepatocytes
sinusoidal endothelial cells
kupffer cells
stellate (ito) cells
11
Q
What is the role of the stellate cell?
A
Storage of fat, vitamin (A in particular), fibrous tissue metabolism
12
Q
What makes up the portal triad?
A
Portal vein
hepatic artery
bile duct (and lymphatics)
13
Q
Identify
A
Top: Portal triad
Bottom: Central Vein
14
Q
In the liver acinus, where is the highest oxygen tension?
A
Zone I
15
Q
Identify the indicated structures.
A
Green = Zone I
Orange = Zone II
Red = Zone III
16
Q
From the portal triad, describe the flow of blood.
A
Hits zone one first, highest O2 concentration here.
Goes then to zone II and then Zone III, before finally reaching the central vein to drain.
17
Q
What zone has the lowest O2 concentration?
A
Zone III
18
Q
What is the “supporting structure” for the hepatocytes?
A
Reticulin
19
Q
List as many of the metabolic functions of the liver as you can.
A
- Formation and excretion of bile during bilirubin metabolism
- Regulation of carbohydrate homeostasis
- Lipid synthesis and secretion of plasma lipoproteins
- Control of cholesterol metabolism
- Formation of urea, serum albumin, clotting factors, enzymes, and numerous other proteins
- Metabolism or detoxification of drugs and other foreign substances
20
Q
What are the major causes of liver injury?
A
- Infection
- Immune mediated
- Drug and Toxin
- Metabolic
- Genetic
- Autoimmune cholangiopathy
21
Q
What are two big drug/toxin causes of liver injury?
A
Acetaminophen
Ethanol
22
Q
What are three examples of genetic causes of liver injury?
A
–Hemochromatosis
–Wilson’s disease
–Alpha-1 antitrypsin deficiency
23
Q
What are two examples of autimmune cholangiopathy?
A
–Primary biliary cirrhosis
–Primary sclerosing cholangitis
24
Q
What is the definition of acute liver failure?
A
Evidence of coagulation abnormality and any degree of mental alteration in a patient without pre-existing cirrhosis and with an illness less than 26 weeks duration.
25
Acute Hepatic Failure is onset of liver failure within 26 weeks after onset of new liver disease defined by evidence of impaired liver function with increased PT and encephalopathy.
What amount of hepatocytes must be lost to manifest this way?
What is the mortality rate?
What is the treatment approach?
Caused by: \>80% loss of hepatocytes
Mortality rate: 40-80%
Approach: Hospitalize and consider liver transplantation
26
What does fulminant hepatic failure describe?
used to describe the development of encephalopathy within 8 weeks of the onset of symptoms
27
What are five manifestations of acute liver failure?
1. •Jaundice
2. •Neurologic symptoms
3. •Encephalopathy
4. •Portal hypertension
5. •Hepatorenal syndrome
28
What can the presentation of hepatic encephalopathy look like?
•can range from sleep disturbance --\> lethargy --\> deep somnolence --\> coma
29
What type of neurologic symptoms can acute liver failure cause?
•symptoms can include a asterixis (flapping tremor) and hyperactive reflexes.
30
What is hepatorenal syndrome triggered by?
* thought to be triggered by vasodilation in the splanchnic circulation leading to decreased renal perfusion and glomerular filtration.
31
How do we determine the extent of hepatocyte injury in the lab?
AST, ALT
32
What laboratory tests do we use to identify cholestatic biliary tract dysfunction?
–Serum bilirubin (direct and indirect)
–Alkaline phosphatase
33
What do we use to assess the sythentic capabilities of the liver?
What are the half lives of these things?
–Serum albumin (20 day half life)
–Coagulation factors (5-48 hrs half life)
34
Liver failure may follow acute injury or chronic injury, but may also occur as an acute insult superimposed on an otherwise well-compensated chronic liver disease.
What is the mnemonic for causes of acute liver failure?
–A: Acetaminophen, hepatitis A, autoimmune hepatitis
–B: Hepatitis B
–C: Hepatitis C, cryptogenic
–D: Drugs/toxins, hepatitis D
–E: Hepatitis E, esoteric causes (Wilson disease, Budd-Chiari)
–F: Fatty change of the microvesicular type (fatty liver of pregnancy, valproate, tetracycline, Reye syndrome)
He said he wasn't sure if this would be worth a shit though, so hey, whatever.
35
Liver failure entails what serious and potentially fatal sequelae?
Coagulopathy
encephalopathy
Portal HTN
Esophageal Varices
Hepatorenal syndrome
Portopulmonary HTN
36
What determines the presence of chronic hepatitis?
Persistent liver disease (AKA)
lasting for more than 26 weeks
37
Hepatitis may evolve through fibrosis to what outcomes?
1. •Cirrhosis
2. •Complications of cirrhosis
3. •Hepatocellular carcinoma
38
Acute hepatitis may be clinically asymptomatic with only abnormal LFTs. If symptomatic what can been seen for the following?
1. Constitutional symptoms
2. Physical Findings
3. Rare findings
1. Nonspecific constitutional symptoms
* –Fever
* –Nausea/vomiting
* –Fatigue
2. Physical findings
* –Jaundice
* –Tender liver
* –Altered mental status/coma (hepatic encephalopathy)
* –Bleeding
3. Uncommon
* –Headaches, myalgias, arthritis
* –Rash, urticaria, arthritis
39
Symptoms of acute hepatitis can be proportional to what?
Degree of ALT/AST elevation
40
Describe the AST/ALT levels in chronic liver disease
•Liver injury tests (AST/ALT) tend to be low to moderate but persist for months/years
41
Daily symptoms in chronic liver disease may be mild or even absent. Does regeneration occur?
What happens in the long run?
* Hepatic regeneration occurs but may or may not equal injury
* Long-term: new symptoms may arise due to liver dysfunction and/or as consequences of cirrhosis
42
What are 7 histological manifestations of liver injury?
1. •Inflammation
2. •Hepatocellular injury (reversible)
3. •Necrosis and apotosis (cell death)
4. •Regeneration
5. •Fibrosis
6. •Neoplasia
43
Identify
Top: Portal tract
Left: Sinusoids
Right: Central Vein
44
In chronic liver failure, what inflammatory cells will you see?
Lymphocytes - lots in the portal tract
45
Where are the inflammatory cells in acute hepatitis?
Lobular areas
46
What do you see here?
What are four common causes of this?
Hepatocellular injury with steatosis.
1. non-alcoholic fatty liver
2. alcoholism
3. drugs
4. viruses
47
What is microvesicular steatosis associated with?
Reye syndrome
Tetracycline toxicity
fatty change of pregnancy
48
What is a relatively new group of patients that has a high level of steatosis?
DM II
Obese
Metabolic syndrome
49
What is shown here?
What are three causes?
Microvesicular steatosis
1. Reye syndrome
2. tetracycline toxicity
3. fatty change of pregnancy
50
This slide shows hepatocellular injury. What is indicated by the arrows?
What is this often associated with?
Top two arrows = Ballooning degeneration
Bottom arrow = clumped intermediate filaments-mallory hyaline
ETOH abuse
51
What is shown here?
What do the arrows show?
Acute hepatitis
Top arrow = apoptosis
Bottom arrow = Lobular disarray with mononuclear cell infiltrates
52
What is shown here?
What do the arrows indicate?
What does the arrow head indicate?
hepatocellular biliary injury - cholestasis
Arrows = Intracytoplasmic cholestasis
Arrow head = bile in dilated bile canaliculus
53
How long does it take for macros to clear apoptotic bodies in the liver?
6-8 hours
54
What is shown here?
Hepatocellular biliary injury - cholestasis
Arrow indicates a distended bile canaliculus filled with bilirubin.
55
What do the two sets of arrows indicate?
Top = hepatocyte necrosis with eosinophilic remnants of cords and the occasional pyknotic hepatocyte nuclei.
Bottom = viable hepatocytes
56
What are some causes of acute cellular necrosis in the liver?
Drugs
certain mushrooms
Viral infection
Autoimmune
57
What is this?
What is it indicative of?
Portal inflammation
Chronic viral hepatitis
58
What is shown here?
What is it common in?
What is this previously known as?
* Portal Inflammation with Interface Hepatocyte Injury (Chronic Injury Pattern)
* Interface hepatitis seen in chronic viral hepatitis
* previously known as "piecemeal necrosis"
59
What is shown here?
Cirrhosis - trichrome stain of the liver demonstrates "bridging fibrosis" and completely surrounded nodules
60
What is "bridging fibrosis"?
Fibrosis connecting two or more portal zones
61
Hepatic stellate cells are normally quiescent fat/vitamin A storing cells. In several forms of acute and chronic injury, stellate cells can become activated and transform to what?
Highly fibrogenic myofibroblasts
62
If acute or chronic hepatitis persists, scar deposition begins, often in what place?
Space of Disse
63
What is the major parenchymal source of excess collagen under abnormal conditions?
stellate cells
64
What is shown here?
Cirrhosis with parenchymal extinction
65
What is parenchymal extinction d/t?
Microscopic areas of ischemia after vascular inflammatory injury and occlusion.
66
In addition to the parenchymal extinction what other changes are seen in cirrhosis?
Scarring in areas of hepatocyte dropout and collapse of the lobular unit (PV and CV come close together)
Hepatocyte hyperplasia of viable cells elongate the scars into fibrous septae and bridging fibrosis.
67
What is shown here?
What do the arrows indicate?
What is contained in the structure indicated by the arrows?
1. Cirrhosis
2. Fibrous septa
3. Contains preexisting portal tracts, hepatic veins and condensed stroma
68
What characterizes cirrhosis?
Diffuse nodular regeneration surrounded by dense fibrotic septae with subsequent parenchymal extinction and collapse of liver structures.
69
Cirrhosis is characterized by diffuse nodular regeneration surrounded by dense fibrotic septae with subsequent parenchymal extinction and collapse of liver structures causing pronounced distortion of hepatic vascular architecture which leads to?
Increased resistance to portal blood flow and subsequent portal hypertension.
70
How is cirrhosis classified?
Compensated
Decompensated
71
What is the most common cause of death in compensated cirrhosis?
Cardiovascular disease
(followed by stroke, malignancy, and renal disease)
72
What are the usual causes of death in patients with decompensated cirrhosis?
1. Portal HTN complications
2. Hepatocellular carcinoma
3. sepsis
73
What is a strong prognostic indicator in predicting complications and mortality in patients with both compensated and decompensated cirrhosis?
Hepatic Venous Wedge pressure
74
What is the Child-Turcotte-Pugh classification scheme used for?
Assessment of prognosis of cirrhosis
75
What are the three CTP classes and their associated scores?
A: 5-6 points
B: 7-9 points
C: 10-15 points
76
What are some prehepatic causes of portal HTN?
Portal vein thrombosis
narrowing of the portal vein
77
What are some intrahepatic causes of portal HTN?
What is the most common cause?
Cirrhosis - accounts for most cases of portal HTN
Sinusoidal obstruction
78
What are some posthepatic causes of portal hypertension?
–Severe right-sided heart failure
–Constrictive pericarditis
–Hepatic vein outflow obstruction
79
What are the three mechanisms by which cirrhosis leads to portal HTN?
* Increased resistance to portal flow at the level of the sinusoid
* Compression of the central vein by perivenular fibrosis and parenchymal nodules
* Anastomoses between arterial and portal systems imposing high pressure on a low pressure system
80
What are some clinical consequences of portal HTN?
1. Portosystemic venous shunts
2. Congestive splenomegaly
3. Ascites
4. Hepatic encephalopathy
81
What are four important portacaval anastamoses?
1. Para-umbilical
2. esophageal
3. retroperitoneal
4. Rectal
82
What type of cirrhosis is seen with chronic alcoholism?
Micronodular
83
What type of cirrhosis is commonly seen with hepatitis B or C infection?
Macronodular
84
The development of ascites involves the following components. Describe how each contribute.
1. Sinusoidal hypertension
2. Splanchnic vasodilation and hyperdynamic circulation
3. Decreased plasma oncotic pressure
4. Increased aldosterone
1. Sinusoidal hypertension drives fluid into the space of Disse where lymph flow exceeds thoracic duct capacity
2. Splanchnic vasodilation and hyperdynamic circulation leads to increased perfusion pressure of interstitial capillaries causing fluid extravasation in peritoneum
3. Decreased plasma oncotic pressure - H2O migrates into interstitium
4. Increased aldosterone leads to increased sodium reabsorption and increased intravascular volume
85
What have we here?
Ascites with umbilical hernia from increased abdominal pressure.
86
What are the two chronic liver failure syndromes we covered?
Hepatopulmonary Syndrome
Portopulmonary HTN
87
~30% of patients with cirrhosis get hepatopulmonary syndrome. While the pathogenesis is not known, describe the general mechanism by which this occurs.
1. Intrapulmonary vascular dilation
2. rapid blood flow through pulmonary vasculature
3. poor Hb oxygenation d/t rapid transit
4. hypoxia
88
Potopulmonary hypertension is related to portal HTN and may involve excessive pulmonary vasoconstriction. What are two common complaints a patient with this would likely have?
–Dyspnea on exertion (DOE)
–Clubbing of fingers
89
Chronic hypoxia causes clubbing, what tissues change in the digits?
Is it reversible?
Soft tissue changes have been held responsible for the digital enlargement.
It is reversible.
90
