Symptom To Diagnosis - Jaundice Flashcards
Is conjugated bilirubin REABSORBED by the intestine?
NO!
Fate of conjugated bilirubin in the intestine:
- Can be excreted unchanged in the stool.
2. Can be converted to Urobilinogen by colonic bacteria.
Fate of urobilinogen that is produced by colonic bacteria.
- Can be reabsorbed, entering portal circulation.
- Some is taken up by the liver and re-excreted into the bile.
- Some bypasses the liver and is excreted by the kidney, thus appearing in the urine in small amounts.
UCB is NOT found in the urine. Why?
Because it is bound to albumin.
1st key point in the DDx of hyperbilirubinemia is?
Determining which kind of bilirubin is elevated.
Dark, tea-colored urine means?
Patient has conjugated Hyperbilirubinemia.
Increased bilirubin production - When?
- Hemolysis.
- Dyserythropoiesis.
- Extravasation of blood into tissues.
Impaired hepatic bilirubin uptake - When?
- Heart failure.
- Sepsis.
- Drugs (rifampin, probenecid, chloramphenicol).
- Fasting.
- Portosystemic shunts.
Impaired bilirubin conjugation - When?
Hereditary: 1. Gilbert syndrome. 2. Crigler-Najjar syndrome. Acquired: 1. Neonates. 2. Hyperthyroidism. 3. Ethinyl estradiol. 4. Liver disease (causes mixed hyperbilirubinemia, usually conjugated). 5. Sepsis.
Most patients with UCBemia have?
- Hemolysis.
- Gilbert syndrome.
- HF.
- Sepsis.
CBemia - etiology if normal liver enzymes:
- Sepsis or systemic infection.
- Rotor syndrome.
- Dubin-Johnson syndrome.
CBemia - Elevated liver enzymes - Transaminases more than ALP - Hepatocellular pattern:
- Acute viral or alcoholic hep.
- Alcoholic or non alcoholic steatohepatitis.
- Chronic hel (viral, alcoholic, autoimmune).
- Cirrhosis of any cause.
- Drugs.
CBemia - Cholestatic pattern:
- Extrahepatic cholestasis.
- Intrahepatic Cholestasis (due to impaired excretion):
- Viral hep.
- Alcoholic hep.
- Cirrhosis.
- Drugs and toxins.
- Sepsis.
- Total Parenteral nutrition.
- post-op jaundice.
- Infiltrative diseases (amyloidosis, lymphoma, Sarco, TB).
- PSC.
- PBC.
AST (SGOT) - Aspect of liver assessed + Origins?
Hepatocyte integrity.
- Liver.
- Heart.
- Kidney.
- Skeletal muscle.
- Brain.
- RBC.
ALT - Aspect of liver assessed + origins:
Hepatocyte integrity + Liver.
ALP - aspect of liver assessed?
Cholestasis.
- Liver.
- Bone.
- Intestine.
- Placenta.
For bilirubin >3 Sens and spec of physical exam is?
Sens - 78.4%.
Spec - 68.8%.
For bilirubin >15, Sens of physical exam is?
96.4%.
Traube space?
6th rib superiorly, midaxillary line laterally, left costal margin inferiorly.
The 2 best historical findings in ascites are:
- Increased abdominal girth (LR+ 4.16, LR- 0.17).
2. Ankle swelling (LR+ 2.8, LR- 0.10).
The 2 best physical exam findings are:
- Fluid wave - LR+ 6, LR- 0.4.
2. Shifting dullness - LR+ 2.7, LR- 0.3.
Ultrasound can detect …mL of ascites.
100
Alcoholic liver disease encompasses a broad spectrum of abnormalities:
Steatosis –> Steatohepatitis –> Cirrhosis.
Steatosis - Textbook presentation:
- Usually asymptomatic.
- Normal/mildly elevated transaminases.
- Hepatomegaly is present in 70% of patients with biopsy proven steatosis.
What is the main problem with steatosis?
- Potentiates liver damage from other insults, such as viral hep or acetaminophen toxicity.
- Promotes obesity-related liver disease.
Steatosis - Reversible?
Yes, but… 1 study found that 18% still progressed to cirrhosis.
Steatosis - Cirrhosis develops in …% who continue to drink.
37%.
Alcoholic steatohepatitis - Textbook presentation.
- Fever.
- Malaise.
- Jaundice.
- Tender hepatomegaly.
Alcoholic steatohepatitis - Found in …-…% of heavy drinkers.
10-35%.
Alcoholic steatohepatitis - 3-month mortality:
15% –> Mild alcoholic hep.
55% –> Severe alcoholic hep.
Mayo End-stage Liver Disease (MELD) score - Components:
- Total bilirubin.
- INR.
- Serum creatinine.
MELD score >11 was found to have a sens of …% and a spec of …% for 30-day mortality.
86%.
82%.
Glasgow Alcoholic Hepatitis Score (GAHS) - Components:
- Age.
- WBC count.
- BUN.
- PT/INR.
- Total bilirubin.
Alcoholic steatohepatitis - Transaminases?
Elevated but generally <6-7 times the upper limit of normal.
Alcoholic steatohepatitis - GGT and ALP:
GGT is often elevated.
GGT/ALP is often >2.5.
Alcoholic steatohepatitis - AST/ALT ratio:
Often, but not always >2. (70-80% of cases).
Alcoholic cirrhosis - Prognosis:
5-yr survival:
90% if the patient becomes abstinent.
70% if patient continues to consume alcohol.
30-50% once complications of cirrhosis appear.
MC presenting complain in pancreatic cancer:
Abdominal pain - 80%.
Jaundice in pancreatic cancer - When the caner is in the body or tail?
Due to liver metastases.
Rare presentation of pancreatic cancer:
- Acute pancreatitis.
- Malabsorption.
- Migratory thrombophlebitis.
- GI bleeding.
CA 19-9 for pancreatic cancer:
37-40 –> Sens 76-90%, spec 68-98%.
100-120 –> Spec 87-100%.
>1.000 –> Spec 94-100%.
Pancreatic cancer prognosis:
If resectable –> 5yr survival is still only 10-25%.
How many pancreatic cancers are resectable?
15%.
Median survival for non resectable pancreatic cancer?
6 months.
When is hepatitis UNLIKELY?
When: 1. Nausea. 2. Anorexia. 3. Malaise. 4. Hepatomegaly. 5. Hepatic tenderness. are absent.
Prevalence of hep A in the US:
20-40%.
Hep A - Symptoms in adults and in children <6.
Symptoms develop in 70% of adults.
<30% of children under 6.
Hep A - Incubation period:
25-30d average. 15-49 range.
Course of Hep A:
Incubation for 25-30d –> prodromal symptoms –> Malaise, fatigue, nausea, vomiting, anorexia, fever, RUQ pain –> 1 week later –> Jaundice.
Hep A - How many patients have jaundice and how many have hepatomegaly?
70% –> Jaundice.
80% –> Hepatomegaly.
Hep A - Uncommon EXTRAHEPATIC manifestations:
- Vasculitis.
- Arthritis.
- Optic neuritis.
- Transverse myelitis.
- Thrombocytopenia.
- Aplastic anemia.
Hep A - Fulminant course is more common in?
- Patients with underlying hep C.
2. 1.1% fatality rate in adults >40.
Hep A - Recovery?
85% fully recover in 3 months, and nearly all by 6 months.
Hep A - Transaminases or bilirubin normalize more rapidly?
Transaminases.
Prevalence of hep B:
0.1-2% (low) in USA, Canada, Western Europe.
3-5% (medium) in mediterranean countries, Japan, Central Asia, Middle East, Latin and South America.
10-20% (high) in Southeast Asia, China, sub-Saharan Africa.
Hep B - Clinical manifestations:
70% –> Have subclinical infection or are anicteric.
30% –> Icteric hep.
Hep B incubation period:
1-4 months.
Transmission of hep B in low prevalence areas:
- Sexual.
- Percutaneous inoculation.
- Needlestick.
- Tattooing.
- Body piercing.
- Contaminated blood transfusion.
Transmission of hep B in medium prevalence areas:
Childhood infections occurs from contaminated household objects, via minor breaks in the skin and mucous.
Transmission of hep B in high prevalence areas:
Primarily perinatal, occurring in 90% of babies born to HBeAg(+) mothers - It can be prevented by neonatal vaccination.
Hep B - Clinical course:
- Fulminant in 0.1-0.5%.
- Transaminases normalize in 1-4 months if acute infection resolves.
- Elevation of ALT for >6months indicates progression to chronic hep.
HBsAg:
- Appears 1-10 weeks after acute exposure.
- Should be present in patients with acute symptoms.
- Should clear in 4-6months.
- LR+ 27, LR- 0.2.
HBsAb:
- Appears after disappearance of HBsAg.
2. Window period of several weeks to months between the disappearance of HBsAg and the appearance of HBsAb.
IgM hep B core antibody (IgM anti HBc):
Appears shortly after HBsAg and is the only marker of acute infection detectable during the “window period”.
LR+ 45.
LR- 0.1.
IgM anti HbC can remain detectable for?
2 years and titer can increase during exacerbation of chronic hep B.
Chronic hep B - Textbook presentation:
Manifestation can range from Asymptomatic, to isolated fatigue, to cirrhosis with portal HTN.
Often NO history of acute hep B.
Risk of progression from acute to chronic hep B varies depending on the host:
- <1% when the acute infection is acquired by an immunocompetent adult.
- 90% when the infection is acquired perinatally.
- 20% when the infection is acquired during childhood.
Chronic hep B - What percentage have extrahepatic findings:
10-20% have extrahepatic findings (Polyarteritis nodosa, glomerular disease).
HBsAg - Detectable or not on chronic hep B?
Generally detectable for life (0.5-2%/year become HBsAg).
Risk factors for progression from chronic hep to cirrhosis:
- Alcohol intake.
- Concurrent hep C or HIV infection.
- High levels of HBV replication.
- HBV genotype C.
Chronic hep B - Screening for HCC?
Screening with US and AFP is recommended every 6-12 months.
True cure in chronic hep B:
Rare 1-5%.
Hep C - Textbook presentation:
Most are ASYMPTOMATIC - Jaundice develops in less than 25%.
When symptomatic –> Similar presentation to those of other viral hep and last 2-12 weeks.
Prevalence of hep C:
20% of acute hep.
1.6% prevalence of infection in the USA.
Perinatal transmission occurs in …-…% of cases.
4.6-10%.
Hep C - Average incubation period:
7-8 weeks.
Hep C - Extrahepatic manifestations:
Found in about 75% of patients.
- Fatigue, Arthralgias, paresthesias, myalgias, Pruritus, sicca syndrome are found in >10%.
- Vasculitis 2o to Cryoglobulinemia –> 1%.
- Cryoglobulinemia is present in about 40%.
- Depression and anxiety are more common than in uninfected persons.
Hep C - How many patients have clear the infection within 6 months?
15-40%.
Percentage of patients who have detectable HCV RNA at 6 months and therefore have chronic hep C.
60-85%.
Chronic hep C - Stages:
5 stages: 0 - No fibrosis. 1 - Fibrous expansion of portal tracts. 2 - Periportal fibrosis. 3 - Bridging fibrosis. 4 - Cirrhosis.
Is there a correlation between ALT levels and liver histology?
No correlation.
Percentage of patients with chronic hep C that progress to at least stage 1 over 5 years?
27-41%.
Cirrhosis in chronic hep C:
Develops in 4-24% of patients after 20 years of infection.
Chronic hep C - Predictors to cirrhosis:
- Liver histology (best predictor).
- Age at infection (>40 years of age –> More progression).
- Duration of infection.
- Consumption of alcohol >50g/d.
- HIV and HBV Coinfection.
- Male sex.
- Higher ALT.
- Baseline fibrosis, and possible Steatosis.
Prevalence of different hep C genotypes:
- 5% –> Genotype 1.
- 5% –> Genotype 2.
- 5% –> Genotype 3.
- 15% –> Genotype 4.
Elevated Transaminases - Non hepatic causes:
- Celiac sprue.
- Inherited disorders of muscle metabolism (only AST).
- Acquired muscle disease (AST only).
- Strenuous exercise (AST only).
Hepatic causes for elevated transaminases:
- Alcohol.
- Medication.
- Chronic hep B and C.
- Non alcoholic fatty liver disease.
- Autoimmune hep.
- Hemochromatosis.
- Wilson.
- Alpha-1 antitrypsin.
NAFLD - Textbook presentation p:
Patients are often asymptomatic but sometimes complain of vague RUQ discomfort.
It is common to identify patients by finding hepatomegaly on exam or asymptomatic transaminase elevation.
NAFLD - Definition:
A spectrum of liver abnormalities all of which include hepatic steatosis in the absence of significant alcohol use.
NAFLD - Stages:
- Steatosis - Fatty liver.
- NASH.
- Cirrhosis.
Prevalence of NAFLD:
20-30% –> in Western adults, with only 2-3% being NASH.
70% –> in diabetics.
91% in obese patients undergoing Bariatric surgery, with 37% being NASH.
MCC of abnormal liver test results in the USA:
NAFLD.
NAFLD - Clinical course:
Most patients with pure Steatosis are stable and do not develop progressive liver disease.
About 12-40% develop NASH with early fibrosis after 8-13 years.
NAFLD - Blood tests:
- Transaminase elevation is usually <4 times normal. AST/ALT ratio is usually less than 1, but not if there is advanced disease.
- Serum ferritin is elevated in 50%.
- Alkaline PHOSPHATASE and GGT are often mildly elevated.
Unconjugated bilirubin binds to?
Albumin.