PHRM3520 Liver and Pancreas

What is the largest single organ?

Liver

What are the four vital functions of the liver?

synthesis

storage

metabolism

clearance

What does the liver synthesize?

proteins like albumin

clotting factors

What does the liver store?

absorbs carbohydrates from gut and stores as glycogen

What does the liver metabolize?

lipids and lipoproteins to form cholesterol

excess amino acids and processes byproducts

What are the byproducts of amino acid breakdown?

ammonia

urea

What does the liver clear from the body?

detox and excretion of endogenous (sex hormones) and exogeneous substances (drugs, toxins)

What are the LFTs?

AST and ALT

ALP

bilirubin

albumin

What tests reflect liver injury?

aspartate aminotransferase and alanine aminotransferase

What are the two main categories of liver tests?

cholestatic

hepatocellular

What are cholestatic tests?

measure abnormal excretory function

biliary disorders

What do hepatocellular tests measure?

inflammation and damage to hepatocytes

What lab tests for the liver measure protein synthesis?

albumin

prealbumin

PT/INR

What lab tests measure cholestasis?

bilirubin

ALP

5'-nucleotidase

GGT

What lab tests measure detoxification?

ammonia

Measurement of albumin, prealbumin, PT, and INR provide what?

a direct reflection of synthetic liver function

Why can the synthetic liver function tests not be used to detect mild to moderate liver damage?

liver has enormous reserve and will continue to synthesize normal amounts of protein despite significant damage

What causes inadequate synthetic function of the liver?

cirrhosis

What is cirrhosis?

irreversible scarring of the liver

12th leading cause of mortality

caused by alcohol abuse, inflammation, or massive liver damage

What is the normal range for albumin?

4-5 g/dL

What is the function of albumin?

maintains plasma oncotic pressure and binding/transport of hormones, anions, drugs, and fatty acids

What is the half-life of serum albumin?

20 days

reduced in chronic synthetic dysfunction

What causes less albumin?

systemic inflammation liver produces less albumin

common in critically ill patients

What happens in hyperalbuminemia?

asymptomatic

seen in dehydration/anabolic steroid use

What happens in hypoalbuminemia?

asymptomatic until levels low (<2-2.5 g/dL)

symptoms include peripheral edema, ascites, pulmonary edema

What does hypoalbuminemia affect?

interpretation of total serum calcium and concentrations of highly protein bound drugs like phenytoin

What is the normal range for prealbumin?

17-34 mg/dL

What is the serum half-life of prealbumin?

2 days

more rapidly responsive

smaller body pool

What affects prealbumin levels?

less affected by liver disease or hydration state

more sensitive to protein nutrition

Prealbumin is the best lab test to assess:

nutritional status

commonly used in pts receiving TPN or tube feeding

What is the normal range for PT?

12.7-15.4 sec

What is the normal range for INR?

0.9-1.1 sec

What leads to increased PT/INR?

coagulation deficit

prolonged reaction times

synthetic dysfunction/vit K deficiency

decreased activated clotting factors

How does liver play a role in clotting?

required for synthesis of clotting factors except factor VIII

these require activation with Vit K

T/F Prolonged PT/INR is specific to liver disease

F

If prolonged PT normalizes after Vitamin K given, what is the cause?

malabsorption

malnutrition

warfarin

antibiotics

What is the cause if the PT remains prolonged after Vitamin K?

liver failure

inherited clotting factor deficiency

What is the purpose of getting PT/INR in liver disease?

prognostic data

major liver failure (>80% loss) can cause clotting abnormalities

How quickly does PT respond to changes in hepatic function?

within 24hrs

may be elevated long before other signs of liver failure

can normalize before clinical improvement

What is cholestasis?

deficiency of excretory function in liver

How are bile and liver related?

bile secreted by hepatocytes into larger bile ducts, and empties into duodenum

large lipophilic drugs and toxins are secreted into bile and eliminated fecally

bile also dissolves and absorbs fat-soluble vitamins and nutrients

What are the fat soluble vitamins?

ADEK

What causes intrahepatic cholestasis?

interference with bile secretion

micro and macro scopic bile ducts

What causes extrahepatic cholestasis?

obstruction of large bile duct, usually from stones

What substances accumulate in cholestatic liver disease?

increased bilirubin (jaundice)

increased bile salts (pruritus)

increased deposits of lipids in skin (xanthomas)

T/F Excretory LFTs can not distinguish between intra and extrahepatic cholestasis

T

What are the excretory LFTs?

alkaline phosphatase

5'-nucleotidase

Gamma-glutamyl transpeptidase

bilirubin

What is the normal range of alkaline phosphatase?

33-96 units/L

What is ALP?

group of isoenzymes with unknown function

most in serum comes from liver and bone

What leads to increased ALP?

bile accumulation, increased synthesis, leaks into bloodstream

How long does ALP stay increased after removing bile accumulation?

2-4 weeks

What is the cause of 4x normal concentration of ALP?

cholestasis

Paget disease

infiltrative liver disease

What is the cause of 3x normal ALP or less?

all types of liver disease

What is the normal range for GGT?

9-58 units/L

What is the normal range for 5'-nucleotidase?

0-11 units/L

What is the most common cause of increased 5'-nucleotidase?

hepatic disease

response profile similar to ALP

What is GGT?

biliary excretory enzyme

rarely elevated in conditions other than liver disease

What is the ratio for GGT/ALP that suggests alcohol abuse?

>2.5

How fast does GGT decrease after alcohol intake stops?

concentrations decrease by 50% 2 weeks after stopping

What is the most sensitive test for cholestatic disorders?

GGT

lacks specificity

What does slightly elevated ALP, normal GGT, and normal ALT/AST mean?

pregnancy

non-liver causes

What does moderate ALP elevation, markedly elevated GGT and normal ALT/AST mean?

cholestatic syndrome

What does mild elevation of ALP, mildly elevated GGT and markedly elevated ALT/AST?

hepatocellular disease

What is the normal range for bilirubin?

total=0.3-1.3 mg/dL

indirect=0.2-0.9 mg/dL

direct=0.1-0.4 mg/dL

What is the function of bilirubin?

indirect binds to albumin

conjugated into water-soluble form (direct)

breakdown of heme pigments from erythrocytes

How is bilirubin excreted?

into bile

eliminated thru feces

Why is shit brown?

bilirubin and breakdown products make brown pigment

What does elevated bilirubin cause?

jaundice and icterus

icterus visible when bilirubin >2-4 mg/dL

What causes indirect hyperbilirubinemia?

increased breakdown of rbs or reduced hepatic conversion to direct bilirubin

What are the most common causes of indirect hyperbilirubinemia?

hemolysis

Gilbert syndrome

Crigler-Najjar syndrome

drugs like probenecid and rifampin

What causes direct hyperbilirubinemia?

hepatic or biliary tract disease interfering with secretion of bilirubin from hepatocytes or clearance of bile from liver

When would direct hyperbilirubinemia be markedly elevated?

only in pts with decreased renal function

What can cause injury to hepatocytes?

toxin and drug metabolism

metabolic disorders

infectious agents

What is hepatitis?

histologic pattern of inflammation of hepatocytes

clinical syndrome due to diffuse liver inflammation

What is the normal range for AST?

12-38 units/L

What is the normal range for ALT?

7-41 units/L

Where are AST and ALT located?

inside hepatocytes

released into bloodstream in greater quantities in hepatocellular damage

What are the characteristics of the ALT/AST tests?

very sensitive

may increase even with minor hepatocyte damage

nonspecific

What are the half-lives of AST and ALT?

AST=17h

ALT=47h

What are extremely high AST/ALT associated with?

>1000 IU/L

viral acute hepatitis

severe drug or toxic reactions

ischemic hepatitis

What is the typical ALT/AST ratio?

>2:1

can help diagnose alcoholic hepatitis

Where is AST specifically located?

cardiac muscle

skeletal muscle

brain

lungs

intestines

What does elevated AST without elevated ALT mean?

cardiac or muscle disorder

What is hepatic encephalopathy?

progressive condition associated with accumulation of unprocessed nitrogenous waste

can occur in acute or chronic liver failure

involves diffuse metabolic dysfunction of brain

What is the clinical presentation of hepatic encephalopathy?

mild altered mental status

coma and death

What is the normal ammonia range?

19-60 mcg/dL

levels dont correlate well with hepatic encephalopathy in chronic liver failure

How does ammonia cause hepatic encephalopathy?

liver removes most of ammonia in first-pass

in liver failure ammonia avoids first-pass and gives immediate access to brain

What is the function of the pancreas?

exocrine and endocrine

aids in digestion of proteins, fats, and carbs

produces hormones like insulin and glucagon

What is pancreatic insufficiency associated with?

malabsorption of nutrients

leads to weight loss and severe diarrhea

How much pancreas needs to be destroyed before diabetes or insufficiency develops?

over 90%

large reserve capacity

What is pancreatitis?

inflammation of pancreas

most common disease of pancreas

increasing incidence

What is the clinical presentation of pancreatitis?

severe midepigastric abdominal pain, often radiates to the back

continuous pain

n/v

Most cases of pancreatitis caused by?

gallstones and alcohol

sometimes medications

What lab tests do we do for pancreatitis?

amylase

lipase

What is the normal range for amylase?

20-96 units/L

low sensitivity

What does amylase do?

breaks down starch into individual glucose molecules

mostly originates from pancreas and salivary glands

What is the serum half-life of amylase?

1-2 hrs

concentrations rise within 2-6hrs after onset of pancreatitis

peak at 12-30hrs

What is the relationship between amylase and pancreatitis?

doesnt correlate with disease severity or prognosis

higher amylase indicates greater likelihood of pancreatitis

What can cause artificially low amylase level?

>800 mg/dL

hypertriglyceridemia

What is the normal range for lipase?

4-43 units/mL