Liver & Bilary System Dysfunction, Physiology, Lab Values

liver stores

A large volume of blood, varying with activity and arterial/venous pressure, vitamins A, B12, D, E, K, and iron.

what triggers blood release

released in response to hemorrhage or increased tissue oxygen demand (exercise)

liver’s filter functions

Physical filter: Kupffer cells (macrophages), pit cells (tumor defense), and stellate cells trap/break down bacteria and particulates

Biochemical filter: detoxifies blood from the gut (via the portal vein) and metabolizes drugs/hormones

two phases of the liver's biochemical filter

Phase I (cytochrome P450): hepatic enzymes break toxins into inactive, less lipophilic metabolites via oxidation/hydroxylation.

Phase II: esterification. Metabolites from both phases are secreted into bile and blood, then excreted via the GI tract.

carbohydrate metabolism function

Carbs are digested/absorbed in the gut, travel via portal blood to the liver, and are broken into glucose and glycogen

liver's glucose buffer function

The liver buffers blood glucose by storing excess as glycogen and releasing glucose when levels dip (gluconeogenesis converts non-carbs to glucose).

ammonia metabolism in liver

The liver is the only site where ammonia is cleared from the blood by hepatocytes, which convert it to urea via the urea cycle for renal excretion.

• toxic to the CNS, originating mostly from the colon/kidneys and a little from RBC breakdown

alcohol metabolism in liver

Alcohol dehydrogenase converts ethanol to acetaldehyde; at higher ETOH concentrations, cytochrome P450 also oxidizes ethanol, which is responsible for alcohol tolerance.

bilirubin metabolism

Bilirubin forms in tissues from hemoglobin breakdown and circulates bound to albumin as unconjugated/indirect (lipid-soluble) bilirubin.

In the liver it dissociates and becomes conjugated/direct (water-soluble) bilirubin, which is excreted in bile or urine

liver with vitamin D

Synthesizes it into calcitriol, the bioactive form, which regulates calcium and phosphorus levels.

fat metabolism

Dietary fats are absorbed as triglycerides and transported to the liver; hepatic cells hydrolyze them into glycerol and free fatty acids (used for ATP) or release triglycerides for adipose storage.

The liver also synthesizes fats from carbs/protein, plus cholesterol and phospholipids

albumin

The most common plasma protein, derived from cholesterol and synthesized in the liver; responsible for the osmotic pressure of plasma

• low levels cause peripheral edema and ascites

liver function in blood clotting

It's the primary production site for vitamin K-dependent clotting factors (a long, complex process) and also filters activated clotting factors out of the blood.

bile

Made in hepatic cells and drains via bile ducts; consists of bile acids, salts, and pigments.

It aids fat digestion and buffers GI acids.

It's stored in the gallbladder and released into the duodenum, with 700-1200 mL secreted per day.

gallbladder’s role

Stores and concentrates bile, secreting it into the duodenum via the common bile duct.

• not essential for digestion

what triggers gallbladder contraction

The sphincter of Oddi relaxes when food enters the mouth, and fatty acids in the duodenum trigger gallbladder contraction.

AST

normal 8-20

aminotransferase released from damaged hepatic cell

detects hepatic inflammation/injury/necrosis but is also found in skeletal muscle, kidney, brain, pancreas, lungs, and spleen.

ALT

aminotransferase released from damaged hepatic cell

normal 5-35

more liver-specific

ALP (alkaline phosphatase)

A non-specific indicator of liver disease, bone disease, hyperparathyroidism, or liver/bone tumors

normal range 30-85

Isoenzymes can help pinpoint the source

fractionated ALP indicates

elevates specifically with biliary tree injury (liver/gallbladder bile ducts)

LDH (lactate dehydrogenase) indicates

A non-specific liver test since LDH is found throughout the body (normal range 45-90)

the specific isoenzyme LD5 is elevated with specific liver disease

albumin indicates

Synthesized in the liver from cholesterol

low levels alter osmotic pressure in blood vessels, causing peripheral edema and ascites

Normal range: 3.5-5.5

conjugated (direct) bilirubin

normal blood 0.1-0.3, normal urine 0

elevated indicates hepatic jaundice

unconjugated (indirect) bilirubin

normal 0.2-0.8

elevated indicates prehepatic jaundice

total bilirubin

normal 0.1-1

combination of both conjugated and unconjugated

prothrombin time (PT)

The time for blood to clot via the extrinsic pathway, normal 12-15 seconds

Elevated time increases bleeding risk and reflects liver dysfunction, since the liver synthesizes clotting factors

• it can also be elevated from vitamin K deficiency.

partial thromboplastin time (PTT)

Clotting time via the intrinsic pathway (normal 30-40 seconds)

increases with severe liver disease or anticoagulation therapy

jaundice

Not a disease but a symptom of hyperbilirubinemia (total bilirubin >1.2)

Scleral icterus (yellow eyes) appears with total bilirubin >3, and skin involvement appears with >5-6.

prehepatic jaundice

increased hemolysis (malaria, thalassemia, sickle cell, hemolytic anemia)

no bilirubin in urine, elevated total/unconjugated bilirubin

hepatic jaundice

liver dysfunction (hepatitis, cirrhosis, venous congestion)

bilirubin in urine, elevated total/conjugated bilirubin.

post hepatic jaundice

obstruction (gallstones, bile duct obstruction)

bilirubin variable in urine, elevated total/conjugated bilirubin, pale stools.

cholelithiasis

AKA: Gallstone disease

one of the most common GI diseases in the US (~20 million/year affected, more women than men)

about 75% of gallstones are asymptomatic

risk increases with advancing age

cholesterol stones

(80% of cases): cholesterol hyper saturation in bile forms crystals that aggregate

• can relate to bile stasis or a hypoactive gallbladder

black pigment stones

increased unconjugated bilirubin causes bile salts to aggregate

• can relate to bile stasis or a hypoactive gallbladder

biliary colic pain from cholelithiasis

Occurs only when a stone moves toward the duodenum

epigastric/RUQ pain that can radiate to the right shoulder/upper back (T6-9 distribution)

often with nausea/vomiting, frequently postprandial, with pain to palpation and abdominal guarding

cholelithiasis diagnosis

with a posthepatic LFT pattern, RUQ ultrasound/cholecystogram, or MRCP

cholelithiasis treatment

with bile acid drugs (CDCA/UDCA) to dissolve stones, cholecystectomy, ERCP, or diet modification — though 30-50% recur within 5 years.

PT implications for cholelithiasis

Prevention with regular aerobic activity; post-cholecystectomy care to reduce secondary complications of abdominal surgery; and recognizing the symptoms

cholecystitis

A complication of cholelithiasis — inflammation, distention, or infection of the gallbladder from bile duct obstruction

acute cholecystitis

intense pain, similar to but worse than cholelithiasis

chronic cholecystitis

intermittent but persistent irritation and swelling

cholecystitis signs/symptoms

Pain (more intense than cholelithiasis)

fever

leukocytosis (WBC >12,000)

altered LFTs (increased total bilirubin, AST, ALP)

positive Murphy's sign

cholecystitis treatment

analgesics, antibiotics, cholecystectomy/ERCP, and diet modification.

choledocholithiasis

Stones specifically in the common bile duct (can occur without gallbladder stones)

Causes right periscapular pain, severe biliary colic, post hepatic jaundice, nausea/vomiting, and fever

Ultrasound is less sensitive (MRCP preferred); it's the most common cause of pancreatitis

cholangitis

Infection of the gallbladder, commonly from bile outflow obstruction

Charcot’s triad

fever, pain, and jaundice (plus cholelithiasis symptoms)

Reynold’s pentad

high mortality, Charcot's Triad plus hypotension and mental status changes

• staged 1-3, with stage 3 requiring emergent ICU care

hepatitis

Inflammation of the liver (acute or chronic) from viral infection (A-E, G; CMV, HSV, EBV), alcohol, drugs, or autoimmune disease

• clinical manifestations are similar across causes

stages of acute hepatitis

Incubation phase

prodromal (pre-icteric) phase

icteric phase

recovery phase

prodromal phase of hepatitis

Starts about 2 weeks after exposure and ends at jaundice onset

Symptoms include fatigue/malaise, anorexia, nausea/vomiting (often food-triggered), headache, low-grade fever, RUQ pain, and weight loss (2-4 kg)

Infection is highly transmissible during this phase

icteric phase of hepatitis

Marks jaundice onset as hepatocellular destruction and intrahepatic bile stasis cause hepatic jaundice

Features: dark urine, clay-colored stools, fatigue, worsening pain, mild itching, splenomegaly, enlarged posterior cervical nodes, and LFT changes (elevated total/conjugated bilirubin, bilirubin in urine, increased ALT/AST/ALP

recovery phase of hepatitis

Begins with resolution of jaundice and lasts up to 3-4 months

The virus clears, symptoms diminish, appetite returns (though fatigue persists), and LFTs normalize.

May instead progress to chronic hepatitis (most common with Hep B, C, D), defined as persistent symptoms/inflammation after the acute phase.

Hepatitis A

Fecal-oral transmission (contaminated food/water), highly contagious in the 2 weeks before jaundice.

Diagnosed via HAV antibodies

supportive treatment, vaccine available, excellent prognosis.

Hepatitis B

Blood-blood transmission (sex, IVDA, transfusion, 3rd-trimester mother-to-infant).

Diagnosed via HBV antibodies/antigens; treated with antivirals/interferon/supportive care

Vaccine available (required for most hospital personnel).

About 15-30% develop chronic infection; it's the leading cause of fulminant hepatitis and can progress to cirrhosis/hepatocellular cancer.

Hepatitis C

Blood-blood transmission — the most common blood-borne infection.

Patients are commonly asymptomatic; diagnosed via HCV antibodies.

No vaccine exists, but newer antivirals are available (e.g., Harvoni, Epclusa).

About 80% develop chronic infection and can progress to cirrhosis/hepatocellular cancer.

Hepatitis D

only occurs with Hep B antigen present, similar course to A/B (occasionally more severe)

Hepatitis E

fecal-oral, seen in southeast/central Asia, vaccine available, similar to Hep A but more severe (fatal in 20% of pregnant women)

Hepatitis G

rare, blood-to-blood, variable course

fulminant hepatitis

A rapidly progressing liver inflammation leading to hepatic encephalopathy

rare (<1% of acute viral hepatitis); caused by acetaminophen overdose, drug reactions, HAV/HBV, or hepatic ischemia

LFTs are severely elevated; prognosis is poor (80% mortality), usually requiring transplant

stages of hepatic encephalopathy

Stage I: impaired attention, depression, tremor, impaired coordination, personality changes

Stage II: drowsiness, sleep disorders, poor short-term memory, ataxia, slurred speech

Stage III: confusion, somnolence, nystagmus, clonus, muscle rigidity, hypoactive reflexes

Stage IV: comatose, decerebrate posture, no response to stimuli

cirrhosis

An irreversible inflammatory liver disease causing diffuse fibrosis (bands/nodules) that disrupts liver structure/function, obstructing biliary flow and/or blood flow (causing portal HTN and liver hypoxia). Most commonly caused by alcohol and Hepatitis C; develops over years.

lab patterns in cirrhosis

Elevated AST/ALT, low platelet count, low albumin, increased total bilirubin (conjugated > unconjugated), and elevated ALP

Treatment is supportive, eventually requiring transplant; prognosis is poor without one

portal hypertension

Abnormally high pressure in the portal venous system (normal ~3 mmHg; portal HTN >10 mmHg)

intrahepatic portal hypertension

most common — hepatitis/cirrhosis or thrombosis in liver vessels

post-hepatic portal hypertension

hepatic vein thrombosis, right heart failure

pre-hepatic portal hypertension

portal vein thrombosis/stenosis

esophagus, anterior abdominal wall, and rectum

where do collateral vessels form in portal hypertension

why do collateral vessels form in portal hypertension

allow blood to bypass the blocked/stenosed area, though these vessels can become engorged

esophageal varices

Distended collateral veins causing slow chronic bleeding (anemia, melena) or rupture from gastric acid erosion

• 30-60% mortality

splenomegaly & portal hypertension

Enlargement of the spleen

• one of the complications of portal hypertension

what causes ascites

Accumulation of fluid in the peritoneal cavity from liver and/or kidney dysfunction.

Portal HTN increases hydrostatic pressure, forcing fluid into the abdominal 'third space,' worsened by decreased albumin (altering osmotic pressure) — creating a self-perpetuating loop with the kidneys.

ascites symptoms

Abdominal distension/increased girth (up to 10+ liters if severe), increased respiratory rate (impaired diaphragm excursion), peripheral edema, and risk of bacterial peritonitis ('acute abdomen' with fever, chills, increased WBCs)

ascites treatment

Treat the underlying cause, paracentesis (draining fluid — risks include rapid fluid shifts, infection, re-accumulation), diuretics, restricted salt diet, and albumin replenishment

alcohol intake risk for alcoholic hepatitis

Men: 6-8 drinks/day for 5 years.

Women: 3-4 drinks/day for 5 years.

Very reversible if caught early

alcoholic hepatitis

Alcohol metabolism causes fatty infiltration of the liver (mainly from alcohol's metabolites, the most common cause of cirrhosis) and stimulates autoantibodies against hepatic cells, causing inflammation that leads to necrosis or fibrosis. Irreversible 'web-like' scarring is cirrhosis

alcoholic hepatitis signs/symptoms and treatment

Hepatomegaly (palpable), elevated LFTs, anorexia/weight loss/N&V, vitamin deficiencies (e.g., megaloblastic anemia from folate/B12 deficiency), muscle wasting, jaundice, and abdominal pain.

Treatment: abstinence from alcohol and supportive care

liver warning signs by body system

GI: N/V, diarrhea, clay stools, dark urine.

Neurologic: confusion, sleep disturbances, hyperreflexia.

Integument: jaundice, bruising, spider angioma, pruritus, ascites.

Pain: abdominal/epigastric, RUQ, right periscapular/shoulder pain

neurologic PT considerations with liver disease

mental status changes, balance impairment from altered center of gravity (with ascites)

cardiopulmonary PT considerations with liver disease

increased bleeding risk, hypotension, altered respiratory function, aerobic deconditioning; with varices, avoid Valsalva and consider coughing precautions

integumentary PT considerations

increased bruising, positioning for skin integrity

musculoskeletal PT considerations

muscle wasting and deconditioning

liver transplant conditions

End-stage liver failure and hepatocellular cancer

Orthotopic: cadaveric liver transplant (may be split between a child and an adult)

Living related: a living donor's liver lobe replaces the diseased liver (less common in recent years due to donor complications)

Should be monitored immediately post-transplant

Slowly decreasing LFTs indicate a functioning liver

Bile production is watched

PT (prothrombin time) should also trend downward

signs of transplant rejection

A spike in LFTs (PT and bilirubin) post-transplant, plus jaundice and other liver symptoms, from an autoimmune response attacking the new liver, controlled with immunosuppressants.

Rejection can be acute or chronic

PT considerations after liver transplant

Immunosuppression increases infection risk and myopathy risk

watch for post-abdominal-surgery respiratory complications

edema/ascites should downward trend (ensure good skin care)

promote functional mobility to reduce secondary complications, with attention to pain