Gi #21: Cirrhosis Part I

Front 1

What is Cirrhosis?

What are some of the etiologies (there are many...)

Back 1

Final common histologic appearance of liver due to chronic end-stage liver disease.

Etiologies:
Viral (Hep B,C)
NAFLD
Alcoholic Liver Disease
Autoimmune liver disease
Metabolic (A1AT, Cu, Fe)

Front 2

T or F
Diagnosis of cirrhosis requires biopsy of the liver.

T or F
Knowing the etiology of the cirrhosis is important in late stage of disease.

Back 2

False- sometimes, if there is clear evidence (clinical, labs, and macronodules that can be felt on physical exam) don't need to biopsy.

False- in late stage of disease, etiology doesn't change management. But it can early on (can prevent progression)

Front 3

What is the progression of Cirrhosis (i.e. where does it start and where does it reach in most severe phase)?

What is the "limiting plate"?

Back 3

Starts in Portal region --> progress to Periportal region--> goes beyond the limiting plate --> into parenchyma

Limiting plate = ring of hepatocytes abutting the connective tissue of the portal trial

Front 4

What are some physical exam findings suggestive of cirrhosis?

What are some signs of decompensation?

Back 4

- palpable left lobe of liver
- shrunken, small liver; nodular
- Splenomegaly

Decompensation - Jaundice, Ascites, Asterixes (flapping tremor)

Front 5

Name the following signs of chronic liver disease and STAGE 1 Cirrhosis.

Back 5

Spider nevi (that blanch if you press on center), White nails, Palmar erythema (can be seen normally in pregnant women), and Gynecomastia

*note: unclear as to why, but cirrhosis is associated with elevated estrogen levels (there is excess aromatization of Androsteindione to E2 --> testicular atrophy, impotence, gynecomastia).

Front 6

Name the following signs of chronic liver disease and STAGE 2 Cirrhosis. In what kinds of conditions would we see them?

Back 6

Kaiser Fleishcher ring- deposition of copper in Descemet membrane (around cornea) -- Wilson's disease

Xanthelasma or Xanthomas - especially seen in cholestatic disease, ex: Primary Biliary Cholangitis

Front 7

What signs of chronic liver disease are seen here (STAGE 4 cirrhosis)?

Back 7

Caput Medusae (dilated abdominal wall veins), and Ascites. Muscle wasting (from poor nutrition).

Hyperestrogenemia also causes loss of body hair.

*note above: Dupuytren's contractures (of palmar aponeurosis- associated with Stage 3 Cirrhosis)

Front 8

What lab findings are suggestive of cirrhosis?

What imaging studies would you use to test for cirrhosis?

Back 8

LFTs might be elevated (AST/ALT > 1 especially seen in Alcoholic Liver Disease)
- ↓ albumin, ↑ PT/INR, ↑ bilirubin
- Thrombocytopenia (↓ platelet count from splenomegaly)

U/S (fluid in liver), CT belly (shows shrunken liver, enlarged spleen, venous collaterals).
Nuclear studies (show uptake of radiolabled colloid)

Front 9

Which of the following statements are true about cirrhosis?

A. Understanding the etiology of late disease may dramatically alter management
B. Understanding the etiology of early disease may dramatically alter management
C. There is little value to confirming the diagnosis of genetically inherited disease process in late stage disease
D. Most cirrhosis in the US is caused by unknown causes

Back 9

B. Understanding the etiology of early disease may dramatically alter management

*may decrease the progression of disease

Front 10

Which of the following statements about Cirrhosis are true?

A. Cirrhosis can only be diagnosed by liver biopsy
B. Liver function tests can help determine the etiology of cirrhosis
C. Cirrhosis represents a group of physical and laboratory findings that are final pathway for numerous chronic liver diseases
D. Physical findings in cirrhosis are unique to cirrhosis and not seen in other diseases

Back 10

C. Cirrhosis represents a group of physical and laboratory findings that are a final pathway for numerous chronic liver diseases

Front 11

What does the Child-Pugh classification system tell you? What about MELD?

Back 11

Child-Pugh --> gives you 2-year survival scores (based on presence of ascites, encephalopathy, bilirubin, PT (INR), albumin)

MELD --> algorithm that predicts 3 year mortality (uses numbers, bili, INR, creat)

Front 12

Most forms of cirrhosis will eventually progress to HCC (hepatocellular carcinoma) except ______.

What are some complications of portal hypertension?

Back 12

Wilson's disease (doesn't tend to progress to HCC)

Varices (distended veins), Ascites, bacterial peritonitis, Hepatorenal syndrome (HRS), and Hepatopulmonary syndrome

Front 13

What makes up the blood supply TO the liver? What is the pressure of each component of this system?

What three things make up the bile duct? Ischemic insult to the liver will most affect what zone of the liver?

Back 13

Portal vein (2/3rd of inflow, low pressure 7 mmHg), and Hepatic artery (1/3rd of inflow, high pressure 100 mmHg).

Portal triad = Hepatic artery + Portal vein + Bile Duct.
Ischemic injury will affect region near central vein, i.e. Zone 3, (because it is farthest away) from the portal triad.

Front 14

2 Formula's for portal blood flow:

Ohm's law
Poiseuille's law

Back 14

Ohms ΔP = F x R (flow x resistance)

Poiseuille's R = 8nL / πr^4

Front 15

How does portal hypertension develop?

Back 15

1. Increased Resistance to portal flow (fibrosis, active vasoconstriction)

2. Increased inflow from portal veins (splanchnic vasodilation --> low effective blood volume --> activation of Renin/Ag --> plasma volume expansion

Front 16

Portal hypertension is contributed to by which of the following?

A. Decreased resistance to portal flow
B. Hepatic vascular endothelial vasodilation
C. Splanchnic vasoconstriction
D. Increased portal venous inflow

Back 16

D. Increased portal venous inflow

*remember, increased resistance to portal flow, hepatic vascular VASOCONSTRICTION, and splanchnic VASODILATION will lead to increased venous inflow

Front 17

Contributors to decreased effective circulating blood volume in cirrhosis include:

A. Portosystemic shunts
B. Endotoxemia
C. Increased splanchnic and systemic NO synthesis
D. Splanchnic dilation
E. All of the above

Back 17

E. All of the above

Portosystemic shunt, Endotoxemia/Bacteria, Increased splanchnic NO synthesis, splanchnic dilation --> can cause low splenic effective blood volume (leading to volume expansion).

Front 18

Give and example of each of the following:

1. Pre-sinusoidal
2. Sinusoidal
3. Post-sinusoidal
4. Post-hepatic

Back 18

1. Pre-sinusoidal: Extrahepatic = portal vein thrombosis, compression. Intrahepatic = sarcoid, PBC

2. Sinusoidal: cirrhosis, alcoholic hepatitis

3. Post-sinusoidal: Budd Chiari syndrome, VOD (veno-occlusive disease)

4. Post-hepatic: Congestive heart failure, Restrictive cardiomyopathy (R-sided pressure --> back pressure)

Front 19

How do you measure Portal Hypertension (pressure)?

How can you use this to determine if a patient's varices will bleed?

Back 19

Do a wedge pressure (within the hepatic veins)= WHVP
and a Free hepatic venous pressure (i.e. hepatic veins leading to IVC) = FHVP

HVPG (Hepatic venous pressure gradient) = WHVP - FHVP

HVPG >12 = varices may bleed

Front 20

What is the WHVP, FHVP, and HVPG (hepatic venous pressure gradient) in the following types of portal HTN-

Pre-hepatic
Pre-sinusoidal
Sinusoidal
Post-sinusoidal
Post-hepatic

Back 20

Pre-hepatic = all normal
Pre-sinusoidal = all normal
Sinusoidal = ↑ WHVP, normal FHVP, ↑ HVPG
Post-sinusoidal = ↑ WHVP, normal FHVP, ↑ HVPG
Post-hepatic = ↑WHVP, ↑FHVP, normal HVPG (because it cancels out)

Front 21

How does portal HTN lead to the development of varices?

What is the danger of GE (gastroesophageal varices)?

Back 21

Portal HTN --> high volume, and high pressure blood tries to go through past of least resistance.

Flows through portal-systemic collaterals where blood pressure is lowest (may recanalize embryonic veins leading to caput medusae, or cause GE varices).

GE varices can bleed --> mortality

Front 22

What action would be appropriate if you found no evidence of varices on upper endoscopy?

What if someone had a grade I (2nd panel) varices?

Back 22

No varices--> do EGDs every 2-3 years (or ever year if decompensated)

Grade I varices --> Primary prophylaxis (medications such as B-blockers, nitrates)

Front 23

How do meds such as propranolol and nadolol work to treat GE varices?

Back 23

↓ portal pressure --> ↓ variceal wall tension and less likely to bleed

Non-cardiospecific B- blockers --> block splanchinc vasodilation (B2) causing arteriolar vasoconstriction. Decrease portal inflow.

Block cardiac receptors (B1) --> leading to ↓ heart rate and cardiac output. Decrease portal inflow.

Front 24

How do nitrates help in portal hypertension?

What procedure is shown above and for what grade of esophageal varices would it be appropriate?

Back 24

Nitrates- non liver specific VENODILATORS, decrease MAP (can ↑ mortality if used alone)

This is Banding (or endoscoping ligation)- basically chocking the varix with a band till it necroses. Used in Grade 2-3 varices or in case of Acute bleed.

Front 25

What are different procedural (non-pharmacologic) ways that you can treat a bleeding varices?

Back 25

- temporary balloon tamponade (the helmet technique where you blow up balloon and use it to compress vessel in stomach).

- endoscopic sclerotherapy

- esophageal variceal (band) ligation

- Splenorenal shunt (join splenic vein to left renal vein, ↓ pressure in portal system)- controls bleeding in 90% of patients

Front 26

What is TIPSS?

How do somatostatin analogs and Vasopressin help decrease risk of bleeding varices?

Back 26

TIPSS = IR procedure (transjugular intrahepatic photosystemic shunt). Shunt put between hepatic vein and portal vein. ↓ Pressure in portal system.

Somatostatin analog (Octreotide)- inhibit GI hormones (VIP, gastrin, etc.) that normally cause splanchnic vasodilation.

Vasopressin - vasoconstriction (give with NTG because it can constrict the heart blood vessels as well).

Front 27

What do the following endoscopic signs have in common?

Back 27

They are "Red signs" (predictors of variceal bleeding)- ex: Red wale sign, Cherry Red spots, Mamilla sign (platelet plug), and Active bleed

Front 28

Therapy for esophageal varices involves:

A. Agents that increase portal inflow
B. Agents that increase the HVPG
C. Nonselective beta-blockers which lead to splanchnic arteriolar vasoconstriction and decrease in portal inflow
D. Nitrates which increase MAP and portal inflow

Back 28

C. Nonselective beta blockers which lead to splanchnic arteriolar vasoconstriction and decrease portal inflow

Front 29

Therapy of bleeding esophageal varices may include:

A. Balloons which directly compress the blood vessels
B. Octreotide which blocks hormones which cause splanchnic vasoconstriction
C. Vasopressin analogues/vasoconstrictors
D. Endoscopic techniques to stop bleeding
E. All of the above

Back 29

E. All of the above

Front 30

What is this condition? Where in the body is it seen?

Back 30

Gastric antral vascular ectasia (GAVE)- i.e. Watermelon stomach. Dilated blood vessels seen in the stomach.

Can be a result of portal hypertension. Tends to be localized in the ANTRUM of the STOMACH.