PHRM3550 Liver

What are the key partakers that can be used to assess liver disease?

ALT

AST

ratio indicates injury

What is portal hypertension?

alters hepatic blood flow

can be induced by cirrhosis

How does portal pressure work normally?

low pressure venous capillary bed in the parenchyma and functional zones of the kidney

bathes cells in blood and lets it percolate

Mechanism of portal hypertension

elevation in venous bp

results in blood bypassing liver and going back into the systemic circulation

What is caused by portal hypertension?

loss of protective and clearance function

abnormalities in renal salt and water

increase in risk of GI hemorrhage

blood from Gi is filtered less effectively

Symptoms of Liver Failure

yellowing of eyes and skin (jaundice)

itching

fatigue

loss of appetite

GI bleeding

encephalopathy

What is encephalopathy?

altered mental status due to liver failure

from failure of liver to clear poisons

malabsorption of vitamins

associated with coagulopathy

What is the manifestation of an issue with diminished energy generation and substrate conversion?

intermediary metabolism of carbohydrates is altered

alteration in lipid metabolism

change in protein metabolism

What is the manifestation of alterations in intermediary metabolism?

hypoglycemia from decrease in liver mass

hyperglycemia from portal-to-systemic shunting and decrease in post-prandial extraction of glucose

What is the manifestation of alterations in lipid metabolism?

fatty liver

dysfunction in lipoprotein function

change in bile flow

What does a dysfunction in lipoprotein function lead to?

deposition of cholesterol and triglyceride

What effect does a change in bile flow have?

from destruction of bile ducts

leads to decrease in lipid clearance

hyperlipidemia and xanthoma's

Xanthoma's

collection of cholesterol

can show up on skin

associated with hyperlipidemia

What does a change in protein metabolism cause?

altered mental status from decrease in amino acid metabolism

alteration in protein concentration and oncotic pressure

What does an alteration in protein concentration and oncotic pressure cause?

water retention

induce hepatic encephalopathy

alterations in ammonia

What does loss of solubilization and storage functions cause?

cholestasis

cholesterol issues

hemolysis

What is disordered secretion?

buildup of cholesterol and failure of bile secretion

Causes of disordered secretion

obstruction from formation of gallstones

leads to cholestasis

What is cholestasis?

condition where bile is blocked and doesnt flow from liver to duodenum

happens with little change in AST/ALT

Manifestations of cholestasis

cant solubilize lipids and fats

malabsorption of cholesterol and other fats

bile salts build up and are toxic

causes gallstones and jaundice

What is jaundice?

aka icterus

accumulation of bilirubin in ECF

What are the symptoms of jaundice?

urine is dark in color

yellowing of body parts like eyes and skin

What does a decrease in bile lead to?

deposition of cholesterol in skin

xanthoma and itching

How does hepatic disease affect the clearance functions?

altered metabolisms of ammonia

altered hormone clearance-> more hormones in body

altered sodium and water balance

cant clear bacteria and endotoxins

How does a liver disease affect clearance of bacteria and endotoxins?

usually cleared by Kupffer cells

can lead to severe systemic infection (sepsis)

How does liver disease affect metabolism of ammonia?

liver cant detoxify ammonia to urea

leads to hepatic encephalopathy

What increases ammonia?

increased protein intake

GI bleeding

systemic inflammation in response to infection

How does liver disease affect sodium and water balance?

often develop concurrent renal issues from difficulty excreting water

leads to hepato-renal failure

What is acute hepatitis?

liver inflammation of an abrupt onset characterized by liver cell death

What are the common causes of acute hepatitis?

viruses

all produce similar illness

isoniazid

ethanol

What is the clinical presentation of hepatitis?

variable

can be asymptomatic

sometimes only verified by clinical tests (AST/ALT)

cholestasis

hepatocyte necrosis

Symptoms of acute hepatitis

fatigue

weight loss

vomiting

right upper quadrant pain

jaundice

fever

splenomegaly

ascites

What causes cholestasis?

caused by obstruction, malignancy, metabolic disorders

What causes viral hepatitis?

Hep A

Hep B

Hep c

Hep D

Hep E

What is Hep A?

directly kills hepatocytes

induces immune response

spread through fecal-oral

usually mild in comparison to other viruses

can cause massive hepatocellular necrosis

What is Hep B?

transmitted by several routes

doesn't kill cells

most cases asymptomatic

How is Hep B transmitted?

sexual contact

contact with infected blood

bodily fluids

What does Hep B do to cells?

doesnt kill

infects

cells die from immune response

What are the symptoms/presentation of Hep B?

mild disease progression

excessive immune response may lead to failure

What is Hep C?

similar to Hep B but much greater proportion of cases progress to chronic hepatitis

How is Hep C transmitted?

blood

bodily fluid

needles

sexual intercourse

How is Hep C worse than Hep B?

causes more life-threatening consequences

higher incidence of end-stage liver disease

most common cause for liver transplantation

What is Hep D?

needs Hep B to work

much worse than Hep B

How does Hep D work?

risk factor for Hep D is Hep B

vaccination against Hep B protects against Hep D

What are the high risk groups for Hep D?

Hep B infected

injection drug users

hemophiliacs

What is Hep E?

unclassified RNA virus

spread via fecal-oral

may be cause of idiopathic hepatitis

What is toxic hepatitis?

acute hepatitis mostly caused by drugs

responsible for most cases of acute

incidence has been rising (acetaminophen most common)

What drugs cause acute toxic liver failure?

bromfenac

acetaminophen

troglitazone sulfate

HMG-CoA reductase (statins)

What are the signs of viral hepatitis?

cryoglobulinemia

What is cryoglobulinemia?

blood contains large amounts of protein called cryoglobulin

proteins become insoluble at low temps

precipitates block vessels and causes splotches

typically with Hep C

How does ethanol cause alcohol hepatitis?

causes indirect and direct injury

gets oxidized to acetaldehyde and then acetate

alters generation of NADH and ATP levels

What does ethanol-induced liver injury lead to?

fatty acid synthesis

fat accumulation

hypoglycemia

What role does acetaldehyde play in alcoholic hepatitis?

from oxidation of ethanol

interacts with enzymes

causes direct toxicity

What is chronic hepatitis?

inflammatory disease of the liver lasting for more than 6 months

What are the characteristics of chronic hepatitis?

cell necrosis

inflammation

persist for at least 6 months

What are the causes of chronic hepatitis?

viral infections

drugs and toxins

genetic

metabolic disorders

autoimmune disorders

What are the symptoms of chronic hepatitis?

fatigue

malaise

low grade fever

mild intermittent jaundice

mild hepatosplenomegaly

cirrhosis

variceal bleeding

coagulopathy

encephalopathy

ascites

What drugs cause chronic hepatitis?

ethanol

isoniazid

acetaminophen

What are the metabolic disorders that cause chronic hepatitis?

alpha 1 anti-trypsin deficiency

Wilsons disease

immune-mediated

What is the pathogenesis of chronic viral hepatitis?

viruses

prolonged exposure to drugs/toxins

immune response is inadequate to clear

person becomes chronic carrier

viral DNA is integrated into genome

What is the most common cause of chronic liver disease in USA?

chronic viral hepatitis

What causes alcoholic chronic hepatitis?

repeated episodes of acute injury

results in necrosis, fibrosis, and regeneration

leads to cirrhosis

What is non-alcoholic fatty liver disease?

caused by obesity

chronic

manifests as hepatics steatosis

What is the most common disease in western and industrialized world?

non-alcoholic fatty liver disease

What risk factors are strongly associated with non-alcoholic fatty liver disease?

obesity

dyslipidemia

insulin resistant type 2 diabetes

What can non-alcoholic fatty liver disease progress to?

cirrhosis

hepatocellular carcinoma

end-stage-liver disease

What are the clinical manifestations of mild chronic hepatitis?

asymptomatic

anorexia

malaise

fatigue

hepatic symptoms

jaundice

palmar erythema

spider telangiectasia

What symptoms are not present in mild chronic hepatitis?

cirrhosis

portal hypertension

What are the clinical manifestations of severe chronic hepatitis?

variable presentation

cirrhosis

variceal bleeding

encephalopathy

coagulopathy

hypersplenism

ascites

What is cirrhosis?

condition in which liver doesnt function properly due to long term damage

irreversible distortion of normal liver architecture and function

usually slowly progressing over years

What are the characteristics of cirrhosis?

hepatic injury

fibrosis

nodular regeneration

What is the clinical presentation of cirrhosis?

result of hepatocellular dysfunction

portal hypertension

not all pt will develop life-threatening illness

40% diagnosed on autopsy

What is the etiology of cirrhosis?

chronic and progressive

alcohol is most common in US

What causes cirrhosis in other countries?

infectious agents

Hep B

Hep C

chronic biliary obstruction

drugs

What is hepatic fibrosis?

mechanism of cirrhosis

occurs in 3 situations

secondary to inflammation and subsequent activation of immune response

part of wound healing process

What does hepatic fibrosis happen in response to?

agents that induce primary fibrogenesis

Hep B

carbon tetrachloride

What causes alcohol-induced cirrhosis?

chronic alcohol abuse

formation of acetaldehyde that interacts with cellular proteins

What are the clinical manifestations of cirrhosis?

fatigue

loss of vigor

weight loss

GI symptoms like vomiting, jaundice, and tender hepatomegaly

What are the extrahepatic syndromes associated with cirrhosis?

palmar erythema

spider angiomas

parotid and lacrimal enlargement

muscle wasting

gynecomastia

testicular atrophy

menstral irregularities

What is ascites?

fluid in peritoneal cavity leads to an increase in abdominal girth

associated with poor long-term survival in cirrhosis patients

What is the relationship between hepatocellular carcinoma and cirrhosis?

cirrhosis is present in majority of HCC cases

HCC risk increases in cirrhosis pts

Hep B accounts for 50% of all HCC