Liver disease Flashcards
What is the pathogenesis of ascites and how it develops?
Portal hypertension can cause arterial vasodilation of the splanchnic circulation via increased levels of circulating vasodilators (eg, nitric oxide). This, in turn, can result in hypotension, renal hypoperfusion/dysfunction, and ascites (eg, abdominal distension)
What does SAAG stand for?
Serum-Ascites Albumin Gradient.
What is the clinical significance of SAAG?
SAAG helps differentiate portal hypertension-related ascites (transudate) from non-portal hypertension-related ascites (exudate).
How is SAAG calculated?
SAAG = Serum Albumin - Ascitic Fluid Albumin.
What does a SAAG greater or equal to 1.1 g/dL indicate?
Indicates portal hypertension as the cause of ascites.
What does a SAAG <1.1 g/dL indicate?
Indicates non-portal hypertension causes of ascites, such as malignancy or infection.
What are the common causes of high SAAG (≥1.1 g/dL)?
- Cirrhosis
- Heart Failure
- Budd-Chiari Syndrome
- Alcoholic Hepatitis
- Portal Vein Thrombosis
Why does cirrhosis cause high SAAG ascites?
Portal hypertension increases hydrostatic pressure, leading to ascites formation.
Why does heart failure cause high SAAG ascites?
Increased central venous pressure and hepatic congestion raise hydrostatic pressure.
Why does Budd-Chiari Syndrome cause high SAAG ascites?
Budd-Chiari syndrome (BCS) causes high SAAG ascites (≥1.1 g/dL) due to hepatic venous outflow obstruction, which leads to increased sinusoidal hydrostatic pressure and forces protein-poor fluid into the peritoneal cavity while keeping albumin in the bloodstream.
Why does Portal Vein Thrombosis cause high SAAG ascites?
Portal vein thrombosis (PVT) causes high SAAG ascites (≥1.1 g/dL) due to increased hydrostatic pressure in the portal venous system. This pressure forces protein-poor fluid into the peritoneal cavity, while albumin remains in the serum, resulting in a high SAAG.
A 25-year-old man is seen in the emergency department for evaluation of abdominal pain. For the past five days, the patient has had a dull ache in the right upper quadrant that does not change with position or eating. The patient has been drinking 13 beers per day for the past three months and his last drink was two days ago. Temperature is 37.0 °C (98.6 °F), pulse is 126/min, blood pressure is 155/98 mmHg, and SpOz is 100% on room air. On physical examination, the patient is tremulous and anxious. Bloodwork is obtained and results are shown below. Abdominal ultrasound shows increased echogenicity and surface nodularity of the liver with patent venous flow into the liver. The gallbladder and pancreas are not well-visualized due to overlying bowel gas. Which of the following is the most likely diagnosis?
A) Portal vein thrombosis
B) Alcohol-induced cirrhosis
C) Acute cholecystitis
D) Alcohol-induced pancreatitis
E) Alcohol-induced hepatitis
Alcohol-induced hepatitis can manifest in patients with alcohol use disorder as RUQ abdominal pain, elevated transaminases, elevated bilirubin, and elevated prothrombin time (or INR). Careful history and physical examination can help differentiate alcohol-induced hepatitis from other alcohol-induced or hepatobiliary pathologies. This patient with alcohol use disorder presents with RUQ abdominal pain, elevated transaminases, elevated bilirubin, and elevated prothrombin time, indicating alcohol-induced hepatitis. Alcohol use disorder can cause hepatitis (such as in this patient), cirrhosis (with chronic long-term use), and pancreatitis. The patient’s history can generally differentiate between these three etiologies. Alcohol-induced hepatitis (and sometimes cirrhosis) will typically cause RUQ pain that does not change with eating or position. Pancreatitis can cause RUQ or LUQ pain but classically causes epigastric pain that worsens with eating and with lying down. Older age and a longstanding history of alcohol use increases the likelihood of cirrhosis. Younger patients or those with shorter duration of alcohol use are more likely to have hepatitis or pancreatitis. Nausea, vomiting, and weight loss can be common features due to the underlying alcohol use disorder. Patients with any of these three pathologies may also present with alcohol withdrawal symptoms. Physical examination in alcohol-induced hepatitis and alcohol-induced pancreatitis may be similar; however, tenderness to palpation is more likely to be in the epigastric region with pancreatitis. Patients with hepatitis may have scleral icterus or jaundice which would not be present with pancreatitis. Patients may also show signs of alcohol withdrawal including tremulousness, anxiety/agitation, confusion, and hallucinations. Patients with severe alcohol-induced hepatitis may also have asterixis. Patients with cirrhosis will often have other physical examination stigmata of cirrhosis such as ascites, gynecomastia, palmar erythema, and spider angiomata.
What are the common causes of low SAAG (<1.1 g/dL)?
- Peritoneal Carcinomatosis
- Peritoneal Tuberculosis
- Pancreatitis
- Nephrotic Syndrome
- Serositis
A 56-year-old woman presents to the primary care clinic due to weight gain and constipation. She has no significant past medical history and does not drink alcohol or use tobacco products. The patient has gained 5 kg (11 lbs) in the last month and feels very bloated. She has also experienced mild lower abdominal pain. The patient was previously having daily bowel movements and is now only having two bowel movements per week. There is no associated hematochezia, melena, rectal pain, or tenesmus. Past medical history is unremarkable. On physical examination, the patient’s abdomen is distended and a fluid wave is present. There is mild abdominal tenderness to palpation diffusely. Paracentesis is performed and shows a serum-ascites albumin gradient (SAAG) of 0.8. Which of the following tests will most likely provide this patient’s diagnosis?
A) Transthoracic echocardiogram
B) Ascites fluid cell count
C) Liver biopsy
D) Ascites fluid cytology
E) Serum lipase
The serum-ascites albumin gradient (SAAG) is helpful for differentiating between various causes of ascites. SAAG ≥1.1 indicates portal hypertension-related causes (e.g. cirrhosis, spontaneous bacterial peritonitis) and SAAG <1.1 indicates other causes (e.g. malignancy, secondary infection, nephrotic syndrome). Ascites fluid cytology and cell count are useful as well to narrow down the diagnosis. Ascites can occur from intra-abdominal diseases or systemic diseases. The clinical history and physical examination can often tease out the cause. However, paracentesis with ascites fluid analysis provides additional information and is sometimes required to make a diagnosis. The serum-ascites albumin gradient (SAAG) can be used to distinguish between portal hypertension-related causes and other causes of ascites. It is calculated by subtracting ascites albumin concentration from serum albumin concentration. SAAG ≥1.1 indicates that there is mostly fluid (and not much protein) “leaking out” into the ascites and indicates portal hypertension-related causes. In contrast, a SAAG <1.1 implies there is much more albumin “leaking out” into the ascites fluid and is somewhat analogous to exudative pleural effusions (i.e. infection and malignancy are high on the differential diagnosis). SAAG <1.1 indicates causes not related to portal hypertension, such as peritoneal carcinomatosis which is likely in this case, nephrotic syndrome, and secondary (not spontaneous) bacterial peritonitis (e.g. peritoneal dialysis catheter infection). If an ascites fluid cell count shows ≥250 PMN/mm3, this finding is diagnostic of spontaneous bacterial peritonitis. Elevated ascites fluid amylase may indicate acute pancreatitis. Ascites fluid cytology may diagnose peritoneal carcinomatosis. This patient’s presentation is concerning for malignancy, possibly ovarian cancer, which is challenging to detect early. Patients may actually present with weight gain and increased abdominal girth (rather than weight loss) due to significant accumulation of ascites.
Why does malignancy cause low SAAG ascites?
Increased capillary permeability allows high-protein fluid to leak into the peritoneal cavity.
Why does peritoneal tuberculosis cause low SAAG ascites?
Granulomatous inflammation increases protein concentration in ascitic fluid.
Why does nephrotic syndrome cause low SAAG ascites?
Severe hypoalbuminemia reduces oncotic pressure, causing fluid leakage without portal hypertension.
How does SAAG help differentiate cirrhotic ascites from malignancy-related ascites?
Cirrhotic ascites has SAAG greater than 1.1 g/dL (portal hypertension), while malignancy-related ascites has SAAG <1.1 g/dL (non-portal hypertension).
What ascitic fluid findings suggest spontaneous bacterial peritonitis (SBP)?
Neutrophils >250 cells/mm³, positive culture (most commonly E. coli), and SAAG greater than 1.1 g/dL.
When are steroids used in liver failure?
- Steroids are only useful if there’s no active infection or gastrointestinal bleeding
- Severe Alcoholic Hepatitis (Maddrey Discriminant Function ≥32 or MELD >20)
- Autoimmune-mediated hepatocyte destruction
A 54-year-old man is seen in the emergency department for evaluation of abdominal pain and black stool for the past six days. The patient normally drinks 11 beers per day, but his last drink was five days ago due to abdominal pain. The patient is prescribed omeprazole for peptic ulcer disease but does not take this medication. Temperature is 37.2 °C (99.0 °F), pulse is 90/min, blood pressure is 122/81 mmHg, and SpOz is 100% on room air. On physical examination, the patient has normal mentation and no asterixis. There is mild epigastric and right upper quadrant tenderness to palpation. Digital rectal examination shows black stool in the rectal vault without hematochezia. Hemoglobin is 11.1 g/dL, AST is 175 U/L and ALT is 90 U/L. The patient’s Maddrey discriminant function is calculated as 39. Which of the following is the best next step in management?
Patients with alcohol-induced hepatitis should have their Maddrey discriminant function and/or MELD score calculated to assess severity. Patients with DF >32 or MELD >20 should receive (methyl)prednisolone, or pentoxifylline if corticosteroids are contraindicated. This patient with alcohol use disorder presents with right upper quadrant abdominal pain, elevated transaminases, and a severely elevated Maddrey discriminant function, indicating alcohol-induced hepatitis. This patient has known peptic ulcer disease which is likely causing a subacute or chronic upper GI bleed, complicating management of the hepatitis. After diagnosing alcohol-induced hepatitis, the next step is to calculate the Maddrey discriminant function (DF or Maddrey score) which uses total bilirubin and prothrombin time (PT) to calculate a number. If that number is >32, it indicates advanced liver injury and inpatient treatment should be started with intravenous steroids or pentoxifylline if steroids are contraindicated (active GI bleed). The MELD (model for end-stage liver disease) score can also be used, and it uses sodium, creatinine, total bilirubin, and INR. A MELD score >20 indicates advanced injury and the need for treatment. Patients with DF ≤32 and/or MELD less than 20 should receive supportive care without steroids or pentoxifylline. Prednisone is converted to prednisolone in the liver, so patients with alcohol-induced hepatitis should be treated with (methyl)prednisolone rather than prednisone as this conversion may be impaired. In patients with contraindications to corticosteroids (e.g., active Gl bleed, active infection), pentoxifylline should be given instead. In patients receiving treatment, the Lille score should be calculated after several days of treatment to determine response to treatment and whether or not patients should stay on the treatment. The underlying alcohol use disorder must always be addressed in patients with alcohol-induced hepatitis.
What is the pathophysiology of hepatorenal syndrome (HRS)?
HRS is caused by splanchnic vasodilation due to advanced cirrhosis, leading to renal hypoperfusion. In response, the renin-angiotensin-aldosterone system (RAAS) is activated, causing overwhelming renal vasoconstriction, which leads to acute kidney injury (AKI). It is a functional renal failure with no intrinsic kidney damage.
What are the clinical findings in hepatorenal syndrome?
1) Severe liver disease (e.g., cirrhosis, portal hypertension, ascites).
2) AKI with very low urine sodium (<10 mEq/L).
3) Bland urinalysis (no casts, protein, or blood).
4) No improvement with IV fluids (unlike prerenal azotemia).
Why is intravascular volume expansion with albumin the first step in suspected hepatorenal syndrome?
IV Albumin + Terlipressin (or Midodrine/Octreotide/Norepinephrine) is needed because HRS mimics prerenal azotemia, so volume expansion is needed to confirm the diagnosis. Failure to improve renal function with albumin infusion supports HRS. It also helps restore effective circulatory volume and temporarily improves renal perfusion.
What are the diagnostic criteria for hepatorenal syndrome (HRS)?
1) Cirrhosis with ascites.
2) Serum creatinine >1.5 mg/dL (progressive kidney failure).
3) No response to IV fluids (albumin challenge).
4) No other identifiable cause of renal failure (e.g., shock, nephrotoxic drugs, intrinsic kidney disease).
How is HRS differentiated from other causes of AKI in cirrhosis?
- HRS: Very low urine sodium (<10 mEq/L), bland urine, no response to fluids.
- Prerenal AKI: Improves with IV fluids, high BUN/Cr ratio.
- Acute tubular necrosis (ATN): Muddy brown casts, FeNa >2%.
- Glomerulonephritis: RBC casts, proteinuria.
What are the key treatments for hepatorenal syndrome?
1) IV albumin + splanchnic vasoconstrictors (terlipressin, norepinephrine, midodrine, octreotide).
2) Definitive treatment: Liver transplantation.
3) Avoid diuretics, NSAIDs, and nephrotoxic drugs.
What is the role of vasoconstrictors in HRS?
Splanchnic vasoconstrictors (terlipressin, norepinephrine, midodrine, octreotide) help counteract the excessive vasodilation seen in HRS, improving renal perfusion and function.
Why are diuretics avoided in hepatorenal syndrome?
Diuretics worsen intravascular volume depletion and can further exacerbate renal failure in HRS.
What is the only curative treatment for HRS?
Liver transplantation is the definitive treatment, as it reverses the underlying cirrhosis and restores normal renal function.
What laboratory finding is characteristic of HRS?
Very low urine sodium (<10 mEq/L) due to extreme renal sodium retention.
Which conditions commonly precipitate hepatorenal syndrome?
Spontaneous bacterial peritonitis (SBP), gastrointestinal bleeding, severe infections, excessive diuretic use.
