Why is assessing the health of the liver important?
- Health of the liver is important for:
1. Prognosis: important that pts and families know and understand severity/prognosis
2. Operative risk: pt survival of certain elective sxs may be affected by degree of liver func, helping guide tx decisions/risk assessment
3. Eligibility for transplantation: have to be sick enough they would live longer with a transplant than without one
- REMEMBER: the liver can regenerate
What is the best biochemical (or other) test of liver disease?
- No easy measure of hepatic clearance or function
- No highly sensitive or specific test for underlying liver disease
- Liver is a silent organ associated with often non-specific symptoms (such as fatigue)
- All biochemical tests have limitations in predicting function and prognosis
1. Symptoms, physical findings, and lab work have limitations in liver disease assessment
What are some of the complications of liver disease (4)?
- Synthetic impairment: like est. function of a factory
2. Clotting factors
- Cholestasis: impairment of bile flow
- DEC clearance: bilirubin
1. Few clinically useful hepatic clearance tests (Lidocaine): partially due to wide bell-shaped curves in healthy and unhealthy livers
- Portal HTN: portal blood shunted around liver and not processed by it, leading to complications
What do LFT's measure?
- Often biochem measures of hepatocellular injury or death, or impairment of bile flow (i.e., ALT, AST, alk phos)
What are the true liver "function" tests?
- Those that measure clearance (bilirubin) or synthetic activity (albumin)
Provide examples of liver chemistries that detect injury, measure clearance, and test synthetic capacity.
- DETECT INJURY: aminotransferases (ALT, AST) & alkaline phosphatase
- MEASURE CLEARANCE: bilirubin, ammonia (can build up in the blood due to cirrhosis, and cause neurological effects)
- SYNTHETIC CAPACITY: albumin, clotting factors made by the liver (simple blood test for evaluation of liver function)
1. Cholesterol: LATE COMPLICATION of severe dysfunction -> don’t depend on this one; not a great indicator of prognosis
What do aminotransferases measure? Which is more specific for liver injury?
- Aspartate aminotransferase (AST)
- Alanine aminotransferase (ALT)
- INC associated with cell injury or death
1. AST elevation also INC with muscle injury
2. ALT more specific for liver injury
- Marked elevations assoc w/1o hepatocellular injury
What does alk phos measure? In what benign conditions can it be elevated?
- Enzyme derived from bile ducts and correlates with intrahepatic and extra-hepatic injury or obstruction
1. Hard to tell if it is in tiny branches or the trunk: need imaging
- Level associated with INC synthesis -> INC when bile NOT flowing through bile ducts
1. Can be high in pregnancy, growing children, teenagers
- Three important iso-enzymes: gut, liver, bone
What dose cholylglycine measure?
- Serum bile salt
- Correlates with degree of cholestasis, intrahepatic or extra-hepatic obstruction to bile flow
- Cholestasis = impairment of biliary flow
What does GGT measure? Clinical utility?
- Gamma glutamyl transferase/transpeptidase (GGT): enzyme in many tissues, including biliary ductules
- INC with cholestasis, biliary obstruction
1. Also INC with induction by many chemicals, ie Phenytoin (Dilantin: anti-convulsant) and ethanol
- So many meds and chemicals induce GGT that it is LIMITED CLINICAL UTILITY: not a great test
- Isolated GGT elevation is often due to medications or ethanol, rather than liver injury
What do you see here?
What does bilirubin measure? Benign elevation?
- Level represents a balance between input and hepatic removal -> imperfect measure of hepatic clearance and excretory function
1. Some pts w/cirrhosis have normal bilirubin, but when high, it is important
- INC with impaired clearance by the liver or w/intra-hepatic and extra-hepatic obstruction
- Helps advise for prognosis, operative risk, and transplantation
- BENIGN ELEVATION (2-3 range): Gilbert’s syndrome (not that uncommon) -> transport problem, often when fasting (jaundiced post-call, for example)
What does ammonia measure?
- Estimate of nitrogenous waste
- Detoxified in liver by the urea cycle and glutamine synthetase reaction
1. In chronic liver disease, DEC function and porto-systemic shunts around the liver
- Often, but not perfect correlation with hepatic encephalopathy: loss of brain function when a damaged liver doesn't remove toxins from the blood
What are the most important synthetic function tests?
- Prothrombin time (PT): prolonged when clotting factors I, II, V, VII, X deficient (VIII not made by liver)
1. Prolonged when Vit. K deficient
2. Correlates well w/hepatic synthetic func
- International standardized ratio (INR)
- Albumin: 1/2-life about 20d, hepatic synthesis
1. Rapidly changed w/acute illness, malnutrition (which many of these pts have), but still a good test
How could this have been prevented?
- Pt should have received IV injection (instead of IM)
1. Bruise from injection
- Delayed prothrombin time (PT)
What happened here?
- Pt. bled into thigh after arterial blood-gas because delayed PT
What are the components of the Child Pugh score (table)?
- 1 is normal bilirubin and normal PT/INR
- Encephalopathy: ammonia
- Combo of measurements to assess how things are working: least is 5 and most is 15 -> higher = worse prognosis
1. Grade A: 5-6
2. Grade B: 7-9
3. Grade C: 10-15
- Probably don't need to know all of these details...
What are the parameters of the Model of End Stage Liver Disease? What is it used for?
- INR: standardized measure of prothrombin time (PT), hepatic synthetic function
- Creatinine: when this goes up, things aren’t looking good in regards to prognosis -> DEC muscle mass due to malnutrition (leading to low creatinine), so if HIGH = poor prognosis
- This msmt gives you a feel for 3-6-mo prognosis; MELD of 25-30 not good for those who want to make it to the next year
1. Has to be 15 to get on transplant list: this # is what determines priority
- MEMORIZE THIS
What can you conclude from all of this?
- Biochemical tests can give estimates of hepatocellular injury, cholestasis and function
1. No perfect test; all have limitations
2. No accurate hepatic clearance test
- Improved measures of staging pts and estimating prognosis and surgical mortality
2. MELD: has to be 15 to get on transplant list (this is what gives priority on this list)
What is going on here?
- Variceal bleeding: endoscopy of distal esophagus with massive amt of blood flowing
- Distended vein bleeding as aggressively as arterial hemorrhage, but with no pulsation (like a garden hose)
- People can rapidly bleed to death with variceal bleeding: engorged, distended veins
1. Most feared complication of portal HTN
What is the breakdown of blood flow to the liver?
- 30% hepatic artery
- 70% portal vein:
1. Splenic vein
2. Splanchnic circulation
How can cirrhosis cause portal HTN?
- Pressure = flow x resistance
1. Resistance to flow + INC flow = INC pressure in the portal vein
- Cirrhosis INC pressure in the veins going to, and around the liver by INC resistance
1. Fibrosis (scarring) w/distortion of vasculature
2. Live usually like a sponge, but sinusoids (low resistance to flow) changed to capillaries (higher resistance): CAPILLARIZATION
- INC blood flow to stomach and intestines
What is the pathogenesis of chronic portal HTN?
- Pressure in portal vein – pressure in hepatic vein is the gradient: cirrhosis INC this gradient, leading to shunting around liver
1. Portosystemic shunting: shunts around the liver to the heart -> goal of the RBC
- Chemicals (vasoactive peptides) in splanchnic blood supply get in systemic system (like glucagon, a vasodilator) b/c no longer filtered by the liver
1. Really 2 circulations: systemic and portal/splanchnic
- Peripheral artery dilation: systolic BP may be 98 or 100 -> arteries to stomach and intestines dilated, so less resistance to flow in splanchnic arteries, leading to INC splanchnic blood flow, creating the problem
What collateral veinous systems become congested in portal hypertension?
- Venous collaterals form from distal esophagus (azygous system) to rectum
1. Hemorrhoids: esp. after delivering babies (bothersome, but small; can get massive)
- ANTERIOR collaterals via umbilical vein: re-canalization of venous channels in navel, flowing on anterior abdominal wall back to the heart
- POSTERIOR collaterals via retroperitoneal veins, splenorenal shunts -> these collaterals exist, but we don't use them; if splenic v. under high pressure, spleen enlarges/distend, collaterals will form/open
1. Splenic vein is portal
2. Renal is systemic
-NOTE: blood will go the way of least resistance
What are varices?
- Torturous venous collaterals under high pressure underneath esophageal mucosa
- 50% of newly diagnosed cirrhotics
- INC up to 8%/year, and 32% bleed within 2 yrs
- Major cause of death: when these bust, it is a medical emergency
1. Tell pts: if you vomit blood, or have melena, come to ER immediately
What are 2 complications of liver injury that make varices especially dangerous?
- High-pressure bleeding
- THROMBOCYTOPENIA: blood has trouble leaving the spleen, so PLT’s get caught here and don’t last as long
1. Normal PLT count: 100,000-150,000
- COAGULOPATHY: synthetic impairment of clotting factors -> lower production in cirrhosis (INR is a measure of liver function)
- IMAGE: blood in distal esophagus right at GE junc; high pressure from distended vein to stomach
What do you see here?
- Esophageal varices at GE junction; black is the stomach
1. PLASMA coming out: hardly any circulating red cells b/c Hct so low
- This happened b/c pt could not get adequately transfused due to Ab’s to blood donations
- NOTE: when a liver pt vomits blood, take it SERIOUSLY
What is going on here?
- Tx for esophageal varices: suctioning up vein, and putting rubber band on it endoscopically (banding)
What do you see here?
- Portal hypertensive gastropathy: chronic source of bleeding (sometimes rapid bleeding)
- Congestion of stomach mucosa that gives mosaic pattern: portal HTN
1. Blood congesting submucosal area
- May experience bleeding from the stomach, which may uncommonly manifest itself in vomiting blood or melena
1. Similar pattern to GAVE, but in the whole stomach, whereas GAVE tends to be in antrum/lower stomach
What is this?
- Portal hypertensive gastropathy: blood oozing from congested mucosa in body, antrum -> multiple punctate bleeding spots
- Steady oozing of inside lining of the stomach