GI: Cirrhosis and Portal Hypertension

Symptoms of Portal Vein Thrombosis (3)

1. Acute Onset Abdominal Pain 2. Splenomegaly 3. Upper GI Bleeding

Symptoms of Spontaneous Bacterial Peritonitis (7)

1. Fever 2. Abdominal Pain/Tenderness 3. AMS 4. Acidosis 5. Azotemia 6. Hypothermia 7. Hypotension

What is the gold standard for the diagnosis of cirrhosis?

A liver biopsy is the gold standard for the diagnosis of cirrhosis.

Symptoms of Hyperammonemia (3)

1. Asterixis 2. Confusion 3. Coma

How is hepatic encephalopathy treated? (6)

1. Avoid narcotics. 2. Treat infection. 3. Treat GI bleeds. 4. Correct electrolytes. 5. Lactulose 6. Rifaximin

What are the two pressure responsible for capillary fluid shifts?

1. Capillary Hydrostatic Pressure: The hydrostatic pressure drives fluid out of capillaries and into tissues. 2. Capillary Oncotic Pressure: The oncotic pressure is a result of proteins, such as albumin, pulling water into the capillaries, which resists movement of fluid out of the capillaries.

What are the two types of cirrhosis?

1. Compensated Cirrhosis: Compensated cirrhosis is typically asymptomatic for many years and found incidentally with labs or radiological findings. However, stigmata of chronic liver disease can present as well on astute exam. 2. Decompensated Cirrhosis: Symptoms below!

Spontaneous bacterial peritonitis is most often caused by (2):

1. E. coli. 2. Klebsiella. *rarely Strep or Staph

Symptoms of Cirrhosis (11)

1. Fatigue 2. Nausea 3. Poor Appetite 4. Lower Extremity Edema 5. Easy Bruising 6. Jaundice 7. Pruritus 8. Increasing Abdominal Girth 9. Confusion 10. Sleep Disturbance 11. Vomiting Blood

Causes of cirrhosis include: (10)

1. Hepatitis B. 2. Hepatitis C. 3. alcoholic liver disease. 4. non-alcoholic fatty liver disease. 5. hemochromatosis. 6. Wilson's disease. 7. α1 antitrypsin deficiency. 8. autoimmune liver disease. 9. primary biliary cholangitis. 10. primary biliary sclerosing cholangitis.

Clinical Features of Cirrhosis (9)

1. Hyperammonemia: Hyperammonemia can lead to hepatic encephalopathy. 2. Jaundice: The liver is supposed to metabolize bilirubin. When the liver does not do so, then bilirubin rises in the serum, which leads to jaundice. 3. Hypoglycemia: It is the liver's job to break down glycogen and perform gluconeogenesis. However, without gluconeogenesis, hypoglycemia can occur. 4. Coagulopathy: The liver produces clotting factors, so patients with liver cirrhosis can develop an elevated PT and PTT. 5. Hypoalbuminemia: The liver produces albumin. So, in the setting of cirrhosis, patients can develop hypoalbuminemia, which can cause a low oncotic pressure and develops into ascites and edema. 6. Elevated Estrogen: Normally, the liver removes estrogen from the serum. So, in the setting of cirrhosis, the estrogen level can rise. In men, gynecomastia may result. In both men and women, spider angiomata and palmar erythema can result. 7. Portal Hypertension: Portal hypertension can lead to variceal hemorrhage. 8. Spontaneous Bacterial Peritonitis 9. Hepatorenal Syndrome

How are variceal hemorrhages managed? (7)

1. ICU Admission: The patient may require intubation to protect the airway. 2. Broad Spectrum Antibiotics: These patients are prone to lung infections and SBP. 3. Volume Resuscitation (PRBC) 4. FFP: As cirrhosis increases, PT increases. This increases coagulation proteins to decrease risk of further bleeding. 5. Octreotide Bolus with a Continuous IV Infusion 6. Endoscopic Therapy via Banding or Sclerotherapy 7. If banding fails, then TIPS is performed.

Symptoms of Hepatic Encephalopathy (3)

1. Irritability 2. Comatose State 3. Asterixis

Physical Exam Findings of Cirrhosis

1. Jaundice: Jaundice is only present in decompensated cirrhosis, so cirrhosis can be present without jaundice. Further, jaundice is difficult to detect if bilirubin < 2-3 mg. 2. Hepatomegaly: The liver is classically shrunken. 3. Splenomegaly: Splenomegaly is due to congestion from portal hypertension. 4. Muscle Wasting (Stick Figure): Cirrhosis is a catabolic disease. 5. Spider Angiomata: Spider angiomata and palmar erythema are believed to be the result of altered estrogen metabolism. 6. Palmar Erythema: Spider angiomata and palmar erythema are believed to be the result of altered estrogen metabolism. 7. Gynecomastia: About two-thirds of cirrhotics have gynecomastia. 8. Loss of Chest, Axillary, and Male Pubic Hair Pattern 9. Testicular Atrophy: Testicular atrophy results of impotence and loss of sex drive. Further, alcohol can also contribute to testicular atrophy. 10. Fetor Hepaticus: Fetor hepaticus is a pungent breath smell due to increased dimethylsulfide. 11. Ascites 12. Caput Medusa 13. Venous Hum Epigastrium (Cruveilhier-Baumgarten Murmur): A continuous venous hum over caput medusa. 14. Asterixis: Asterixis is a bilateral, asynchronous flapping of a dorsiflexed hand.

How is cirrhosis diagnosed? (3)

1. Liver Biopsy: A liver biopsy is the gold standard for the diagnosis of cirrhosis. However, it is not required when the diagnosis is clear from the history. The biopsy is only performed when the biopsy changes from management. 2. Imaging (US, CT, or MRI): Imaging may show a small, nodular liver with splenomegaly, ascites, and collaterals; however, ist is not sensitive or specific for diagnosis and is more helpful for detection of hepatocellular carcinoma. 3. Clinical Diagnosis: History, physical exam, and labs can be used to diagnose cirrhosis.

What are the two treatments for hyperammonemia?

1. Low Protein Diet: However, a low protein diet is not recommended for patients with cirrhosis any long because, although it lowers the ammonia level, it leads to malnourishment. 2. Lactulose: Lactulose is a synthetic disaccharide that functions as a laxative. In the colon, it is broken down in the colon by bacteria to fatty acids, which lowers the colonic pH. When the colonic pH is lowered, it favors the formation of NH4+ over NH3. NH4+ is not absorbed and is trapped in the colon. This results in increased bowel movements because lactulose is a laxative, and those bowel movements contain ammonia. Therefore, the plasma ammonia concentration falls.

How are not critically ill patients with hepatorenal syndrome treated? (3)

1. Midodrine 2. Octreotide 3. Albumin * The usual treatment duration is two weeks.

Paracentesis Results of Spontaneous Bacterial Peritonitis ( 3)

1. Monomicrobial 2. Low Colony Count 3. Gut Bacteria Positive Opposite of this is probably a perforated gut.

How are critically ill patients with hepatorenal syndrome treated? (2)

1. NorEpi: NorEpi is used to reverse the vasodilatory causing the kidney injury, attempting to increase MAP by 10 mmHg. 2. Albumin (1 g/kg)

How is portal hypertension managed? (3)

1. Pharmacological Treatments: Octreotide, vasopressin (IV), and non-specific beta blockers (propranolol and carvedilol) constrict the splanchnic arteriolar smooth muscle, which reduces portal inflor and thus portal hypertension. 2. Sodium Restriction 3. Diuretics

What are two causes of new or worsening ascites?

1. Portal Hypertension 2. Malignancy

What are the two types of hepatorenal syndrome?

1. Type I 2. Type II

The diagnostic criteria for hepatorenal syndrome include: (4)

1. a rise in creatinine to >1.5 mg. 2. excluding other causes of renal injury, such as shock, nephrotoxin exposure, urine RBC <50 HPF (glomerulonephritis), and proteinuria <500 mg/day (nephrotic syndrome). 3. normal renal US. 4. no improvement after at least 2 days of holding diuretics and volume expansion with albumin.

In order to monitor for hepatocellular cancer in cirrhosis patients, (2) are performed every six months.

1. alpha fetoprotein. 2. imaging (US).

Complications of cirrhosis include: (6)

1. ascites. 2. variceal hemorrhage. 3. hepatic encephalopathy. 4. hepatorenal syndrome. 5. hepatopulmonary syndrome. 6. hepatocellular cancer.

Precipitants of hepatorenal syndrome include: (4)

1. bacterial infections. 2. spontaneous bacterial peritonitis. 3. GI bleeding. 4. aggressive diuresis.

The model for end-stage liver disease (MELD) score utilizes: (4)

1. bilirubin level. 2. creatinine levels. 3. INR. 4. Na+ > 40 = 71% mortality <9 = 2% mortality

Useful studies for a diagnostic paracentesis include: (3).

1. cell count/differential. 2. albumin. 3. total protein.

Two conditions that cause a decreased SVR in combination with an increased total body water include:

1. cirrhosis. 2. HF.

Causes of hepatorenal syndrome include: (4)

1. cirrhosis. 2. portal hypertension. 3. occasionally with alcoholic hepatitis. 4. occasionally with acute liver failure.

Causes of ascites include: (7)

1. cirrhosis. 2. mixed. 3. heart failure. 4. malignancy. 5. nephrotic. 6. pancreatic. 7. tubercular.

Precipitants of hepatic encephalopathy include: (4).

1. narcotics. 3. infection. 3. GI bleeding. 4. electrolyte abnormalities (particularly, K+).

Internal hemorrhoids are caused by collaterals between the (2).

1. superior rectal veins via the portal system. 2. middle and inferior rectal veins via the IVC.

Risk factors for chronic liver disease include: (5)

1. viral hepatitis risk factors. 2. EtOH abuse. 3. family history. 4. prescription/OTC drug history. 5. metabolic syndrome/BMI.

How can a patient have portal hypertension without cirrhosis of the liver?

A patient can have portal hypertension without cirrhosis of the liver with portal vein thrombosis. This is a rare cause of portal hypertension that presents with a acute onset of abdominal pain with splenomegaly.

What is a potential consequence of gastroesophageal varices?

A potential consequence of gastroesophageal varices is that these varices can lead to upper GI bleeding. Without urgent medical care, these varices have a 50% mortality rate.

What is a spider angiomata?

A spider angiomata is a vascular lesion with a central arteriole with small radiating vessel arms. The distribution is in the trunk, face, and arms.

What is a transjugular intrahepatic portosystemic shunt (TIPS)?

A transjugular intrahepatic portosystemic shunt (TIPS) is a treatment for portal hypertension, refractory ascites, or ruptured varices that involves the creation of a channel in the liver that connects the portal vein to the hepatic vein. This bypases scarred liver.

What is the leading cause of cirrhosis in the US?

Alcohol is the leading cause of cirrhosis in the US.

What causes the ascites seen in cirrhosis?

Ascites is caused by a combination of portal hypertension and decreased albumin.

What is ascites?

Ascites is the accumulation of fluid in the peritoneal cavity. In liver disease, it is caused by a combination of portal hypertension and hypoalbuminemia.

What is the most common complication of cirrhosis?

Ascites is the most common complication of cirrhosis. About a 15% will die within one year of onset of ascites, and about 50% die within five years of onset.

______ is the converging end point for all progressive chronic liver disease.

Cirrhosis

What is cirrhosis?

Cirrhosis is irreversible end-stage liver disease that results from many causes of chronic liver disease, including viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. Cirrhosis is caused by recurring liver injury, repair, regeneration, and eventual scarring.

What is the most common cause of ascites?

Cirrhosis is the most common cause of ascites.

What are esophageal varices?

Esophageal varices are tortuous, engorged vessels that are result of portal hypertension. Most blood from the esophagus drain via the esophageal veins to the SVC. However, a small amount of superficial blood is drained via the left gastric vein to the portal vein. There are collaterals between these two vessels. However, with elevated pressure, the collaterals swell, leading to the development of esophageal varices.

True or False: Fluid restriction is useful in the treatment of ascites.

False

True or False: Portal hypertension is not required for ascites.

False

What is fetor hepaticus?

Fetor hepaticus is a pungent breath smell due to increased dimethylsulfide. Normally, dimethylsulfide is removed from the gut by the liver.

What are gastric varices?

Gastric varices are tortuous, engorged vessels that are result of portal hypertension. The short gastric veins drain blood from the stomach fundus to the left gastric vein and splenic vein, both of which are a part of the portal system. When the portal pressure increases, these vessels can swell, leading to bleeding.

What type of varices are most clinically relevant in cirrhosis?

Gastroesophageal varices are most clinically relevant in cirrhosis.

How does cirrhosis appear grossly?

Grossly, cirrhosis presents as a shrunken liver in which liver tissue has been replaced by fibrosis and nodules. The smoother liver surface is replaced with nodules.

What is hepatic encephalopathy?

Hepatic encephalopathy is a potentially reversible neuropsychiatric abnormality in which there is defect hepatic clearance of nitrogenous metabolites. Ammonia is the most likely mediator.

What is the leading cause of cirrhosis worldwide?

Hepatitis B is the leading cause of cirrhosis worldwide.

What is hepatorenal syndrome?

Hepatorenal syndrome is the development of renal failure in a patient with cirrhosis, portal hypertension, and occasionally with alcoholic hepatitis and acute liver failure.

If the serum ascites albumin gradient (SAAG) < 1.1 g/dL, what does this mean?

If the serum ascites albumin gradient (SAAG) < 1.1 g/dL, then there is a small difference between the serum and ascites albumin, which indicates malignancy. Malignant cells lead to a leaky vasculature that allows fluid and albumin into the peritoneum. As a result, the albumin level is similar between the serum and ascites. Other causes can include TB, fungal peritonitis, peritoneal carcinomatosis, and/or nephrotic syndrome.

If the serum ascites albumin gradient (SAAG) > 1.1 g/dL, what does this mean?

If the serum ascites albumin gradient (SAAG) > 1.1 g/dL, then there is a large difference between the serum and ascites albumin, which indicates portal hypertension, as a high pressure drives fluid into the peritoneum, but the vasculature is intact.

How does cirrhosis cause hypoglycemia?

It is the liver's job to break down glycogen and perform gluconeogenesis. However, without gluconeogenesis, hypoglycemia can occur.

Lab Findings of Cirrhosis AST: ALT: Alkaline Phosphatase: Total Bilirubin: PT: Albumin: Platelets: Red Blood Cells: Hemoglobin: Na+:

Lab Findings of Cirrhosis AST: normal to elevated ALT: normal to elevated Alkaline Phosphatase: normal to elevated Total Bilirubin: normal to elevated, but rises with decompensation PT: elevated Albumin: decreased Platelets: decreased (This is due to splenomegaly.) Red Blood Cells: decreased (Alcohol is a bone marrow suppressant. Upper GI bleeding is common.) Hemoglobin: decreased (Alcohol is a bone marrow suppressant. Upper GI bleeding is common.) Na+: hyponatremia in later stages

How does lactulose treat hyperammonemia?

Lactulose is a synthetic disaccharide that functions as a laxative. In the colon, it is broken down in the colon by bacteria to fatty acids, which lowers the colonic pH. When the colonic pH is lowered, it favors the formation of NH4+ over NH3. NH4+ is not absorbed and is trapped in the colon. This results in increased bowel movements because lactulose is a laxative, and those bowel movements contain ammonia. Therefore, the plasma ammonia concentration falls.

What is the leading cause of abnormal liver enzymes in the US?

Non-alcoholic fatty liver disease is the leading cause of abnormal liver enzymes in the US.

How does cirrhosis lead to elevated estrogen levels?

Normally, the liver removes estrogen from the serum. So, in the setting of cirrhosis, the estrogen level can rise. In men, gynecomastia may result. In both men and women, spider angiomata and palmar erythema can result.

How is spontaneous bacterial peritonitis diagnosed?

Spontaneous bacterial peritonitis is diagnosed via ascitic fluid gram stain, culture, and a PMN count > 250 per cc.

What is palmar erythema?

Palmar erythema is an exaggeration of the normal mottling of the palm on the thenar and hypothenar prominences.

What is the common treatment for spontaneous bacterial peritonitis?

Spontaneous bacterial peritonitis is treated with a third generation cephalosporin (cefotaxime) with albumin if hypotensive.

What is the role of stellate cells in the pathogenesis of cirrhosis?

Stellate cells are perisinusoidal cells that serve as the storage site for retinoids (Vitamin A) under normal conditions. However, these cells are activated in liver disease, leading to the release of TGF-β from these cells. Stellate cells proliferate and produce fibrous tissue, serving as a major contributor to cirrhosis.

What is refractory ascites?

Refractory ascites is ascites unresponsive to Na+ restriction and high dose diuretics (400S/160F) or if ascites recurs rapidly after therapeutic paracentesis.

Serum Ascites Albumin Gradient (SAAG) =

Serum Albumin - Ascites Albumin

What is the drug of choice for ascites?

Spironolactone is the drug of choice for ascites. It is a K+-sparing diuretic that blocks aldosterone in the distal tubule.

What is spontaneous bacterial peritonitis?

Spontaneous bacterial peritonitis is an ascitic fluid infection where bacterial in the gut gain entry into the ascitic fluid without evidence of other intra-abdominal secondary source. SBP is considered when the ascitic fluid absolute PMN > 250 cells/mm3. Without early treatment, it can be fatal.

What is the Child-Pugh classification system?

The Child-Pugh classification system is a points system that uses five variables to predict risk and survival, including encephalopathy, ascites, bilirubin, albumin, and PT. The score ranges from 5 to 15, with 5 or 6 being Class A cirrhosis, 7 to 9 being Class B cirrhosis, and 10 to 15 being Class C cirrhosis.

What is the model for end-stage liver disease (MELD) score?

The MELD score is a scoring system for chronic liver disease or cirrhosis that estimates the three-month mortality from liver disease. It utilizes the bilirubin level, creatinine levels, and INR.

What is the consequence of hypersplenism in portal hypertension?

The consequence of hypersplenism in portal hypertension is that hypersplenism can lead to low platelet counts.

How does cirrhosis cause jaundice?

The liver is supposed to metabolize bilirubin. When the liver does not do so, then bilirubin rises in the serum, which leads to jaundice.

How does cirrhosis cause hypoalbuminemia?

The liver produces albumin. So, in the setting of cirrhosis, patients can develop hypoalbuminemia, which can cause a low oncotic pressure and develops into ascites and edema.

How does cirrhosis cause coagulopathies?

The liver produces clotting factors, so patients with liver cirrhosis can develop an elevated PT and PTT.

What is the serum ascites albumin gradient (SAAG)?

The serum ascites albumin gradient (SAAG) is a test of the ascitic fluid for new onset ascites or worsening ascites from baseline. Serum ascites albumin gradient (SAAG) requires a sample of the ascitic fluid via paracentesis. Then, the serum ascites albumin gradient (SAAG) is determined by serum albumin - ascites albumin.

Describe the portal circulation.

The superior mesenteric vein and the splenic vein combine to form the portal vein. Once in the liver, the portal vein divides into the right portal vein and the left portal vein. These divide into smaller branches, forming portal triads. The portal triads then deliver blood into the hepatic sinusoids, enters the central vein, and enters the hepatic veins. The three hepatic veins deliver blood to the IVC then heart.

What is Type I hepatorenal syndrome?

Type I hepatorenal syndrome occurs when creatinine doubles to > 2.5 mg within two weeks. With type I, most patients are oliguric.

What is Type II hepatorenal syndrome?

Type I hepatorenal syndrome occurs when creatinine doubles to > 2.5 mg within two weeks. With type I, most patients are oliguric; however, impairment is less than Type I hepatorenal syndrome.

How is ascites treated? (6)

Treat the underlying disease if possible first. 1. Sodium Restriction: Sodium restriction (2 g/d) leads to volume contraction, which leads to a decrease in ascites. 2. Spironolactone: Spironolactone is the drug of choice. It is a K+-sparing diuretic that blocks aldosterone in the distal tubule. 3. Loop Diuretics: Loop diuretics are second line treatments if spironolactone is not sufficient. 4. Avoid drugs like NSAIDs and, if possible, ACEi and ARBs. 5. Large Volume Paracentesis: The LLQ is a common location at a 45 degree angle. 6. TIPS

How is refractory ascites treated? (8)

Treat the underlying disease if possible first. 1. Sodium Restriction: Sodium restriction (2 g/d) leads to volume contraction, which leads to a decrease in ascites. 2. Spironolactone: Spironolactone is the drug of choice. It is a K+-sparing diuretic that blocks aldosterone in the distal tubule. 3. Loop Diuretics: Loop diuretics are second line treatments if spironolactone is not sufficient. 4. Avoid drugs like NSAIDs and, if possible, ACEi and ARBs. 6. Midodrine: Midodrine can be add to diuretics, which increases blood pressure, urine volume, and Na+. 6. Large Volume Paracentesis: The LLQ is a common location at a 45 degree angle. Partnered with a 6-8 g albumin infusion, there is improved survival, as a patient can develop post-paracentesis circulatory dysfunction. 7. TIPS 8. Liver Transplant

How does cirrhosis cause portal hypertension?

Under normal conditions, blood flows from the portal vein, through the liver, and into the hepatic vein. Then, blood enters the IVC. With cirrhosis of the liver, there is obstructed flow through the liver due to scarring, resulting in an increased resistance and high pressure in the portal vein. This results in portal hypertension.

What are venous anastomoses or collaterals?

Venous anastomoses are vessels in which high portal pressure open, leading to a connection between the portal and systemic veins. Normally, these vessels are small, collapsed vessels that engorge in portal hypertension.

Explain the hemodynamics of cirrhosis.

With cirrhosis, there is a fall in albumin, which results in a decrease in oncotic pressure. Then, fluid can leak out of the capillaries, which can decrease the effective circulating volume of plasma that perfuses tissues. On the other hand, in cirrhosis, vasodilation plays a major role. Cirrhosis leads to an increase in vasodilators, such as NO. This increase in NO leads to vasodilation, particularly of the splanchnic vessels. This leads to a fall of SVR, resulting in a low BP. This activates the sympathetic nervous system, which increases CO. More importantly, the combination of decline in SVR with the decline in oncotic pressure leads to a decrease in effective circulating volume. So, the body responds as if there is low volume and perfusion. There is an increase in RAAS and ADH activity, which leads to Na+ and water retention and an increase in total body water. This leads to ascites and edema.

A hemodynamic hallmark of liver cirrhosis is ______.

a decrease in SVR

Because of gastroesophageal varices, any patient diagnosed with cirrhosis requires _______.

an upper endoscopy done to look for varices and thereafter periodic surveillance for increase in size

Collaterals at the umbilicus result in ______.

caput medusa

Any patient with new onset ascites must receive a _______.

diagnostic paracentesis

A patient who fails hepatorenal syndrome treatment and are candidates for a liver transplant can be considered for _______.

dialysis

Caput medusae are caused by collaterals between _______.

epigastric veins (via IVC) and paraumbilical veins (via portal system)

Collaterals at the rectum result in ______.

internal hemorrhoids

A MELD score of > 15 is used for ______.

liver transplant evaluation

Any patient with large gastroesophageal varices can be placed on _______ to decrease the risk of bleeding.

non-specific beta blockers

Patients with portal vein thrombosis will have a _________ liver biopsy.

normal

Type I hepatorenal syndrome has a ______ prognosis.

poor

Collaterals at the esophagus result in ______.

upper gastrointestinal bleeding

Collaterals at the stomach result in ______.

upper gastrointestinal bleeding