31: Infection, inflammation, and cirrhosis of the liver

the liver is the __________ internal organ

largest

what quadrant is the liver in

RUQ

The livers synthesizes and secretes

bile for fat digestion into the hepatic duct

hepatic duct and pancreatic duct > bile duct > bile to intestines

hepatocytes

functional cells of the liver

Kupffer cells

specific macrophages of the liver that detoxify

Portal triad

lobules (each with a branch of arterial and venous blood vessel) and a portion of a bile duct

liver physiology- 8

1. digestion

2. bilirubin metabolism

3. fat and protein metabolism

4. carbohydrate metabolism

5. Hematologic role

6. endocrine role

7. detoxification

8. other functions

digestion from the liver

Bile salt secretion aid in fat digestion in the small intestine

bile

yellow/green alkaline fluid formed in hepatocytes and some stored in gallbladder for later use. Other bile continues to ileum & colon for excretion.

enterohepatic recycling

Some bile is reabsorbed from ileum into the portal vein, return to liver

bilirubin metabolism

•Bilirubin – from breakdown of RBCs 

•Unconjugated (free/indirect) bilirubin 

•Conjugated/Direct bilirubin

conjugated bilirubin

this is what we need to excrete bilirubin- it makes it water soluble

fat metabolism

•Bile breaks down Fats>Triglycerides>Reenter liver by portal vein

•Liver is a major producer of cholesterol

protein metabolism

•Produces most of the body's albumin

Deamination 

- Breakdown of protein removes nitrogen & converts to ammonia which enters bloodstream integrates with urea & excretes in urine

carb metabolism

glycogenesis

glycogenolysis

gluconeogenesis

glycogenesis

process of storing glucose as glycogen

glycogenolysis

body needs energy and glycogen is broken down

gluconeogenesis

body’s storage of glucose is inadequate

liver converts amino acids and glycerol into glucose

hematologic role

•Synthesizes Fibrinogen & coagulation factors I, II, VI, IX, and X for clotting.

•Prothrombin is produced by the liver with Vitamin K & Bile

•*Without any of these high risk of bleeding!

endocrine role

•Regulation of fat & protein metabolism

•Glucagon – formed in pancreas – acts in liver to stimulate glycogenolysis & gluconeogenesis

detoxification

•Substance ingested>absorbed in GI system>portal vein>LIVER

biotransformation and first pass effect

•substances broken down by the liver into detoxified metabolites before reaching the systemic circulation.

cytochrome P450 system

•enzymes that affect amount of drugs that reach blood stream.

other liver functions

•Stores Vitamins A,D, B12, iron-rich Ferritin, Copper 

•Thrombopoietin – regulates production of platelets

•Angiotensinogen (RAAS)

•Immune protection – immunoglobulins & B lymphocytes

3 causes of liver dysfunction

1.Cholestasis – bile flow obstruction

2.Hepatocellular injury – caused by inflammation

Mixture

main symptom of liver disease

jaundice

hyperbilirubinemia

icterus

high amount of bilirubin in blood stream

causes of hyperbilirubinemia and jaundice

1.Excessive RBC Hemolysis (prehepatic jaundice)

2.Hepatocellular injury (intrahepatic jaundice)

3.Bile duct obstruction (post hepatic jaundice) 

hepatocyte inflammation and infection is most often caused by

viruses, drugs/toxic substances, and/or alcohol use

viral hepatitis causes

hepatitis A,B,C,D,E

CMV

EBV

viral hepatitis

Inflammation of the liver with acute infection leads to increased WBC, increased permeability of hepatocytes cell membranes

>6 months/chronic inflammation increases risk of hepatocellular cancer

toxic hepatitis causes

Acetaminophen***

Alcohol***

Steatosis***

• Infiltration of fat in the liver (characteristic of alcohol abuse)

hepatocyte inflammation and infection

NAFLD (nonalcoholic fatty liver disease) & NASH (nonalcoholic steatosis)

• Etiology unclear

• Typical comorbidities: obesity, hypertriglyceridemia, or diabetes

• Liver becomes infiltrated with fat & fibrotic tissue

bile duct obstruction

blockage of any duct that carries bile from liver to SI

cholestasis

back up of bile

most common cause of bile duct obstruction

gallstones

changes in bowel habit with liver disease

steatorrhea- white color

some other signs of liver disease

Jaundice

Dark urine

pruritis

ascites- shifting dullness

sclera is a yellow color

skin changes

what skin changes will you see with liver disease

spider angioma

caput medusa over abdomen

lab tests that diagnose liver disease

Liver enzymes: ALT, AST

ALK Phos, Direct & Indirect Bilirubin, Albumin, Prothrombin levels, Ammonia levels, Hepatitis Serology Panel

gold standard for diagnosis of stages & severity of liver disease

liver biopsy

hepatitis agents

A, B, C, D, E

CMV

EBV

nonviral hepatitis

toxic chemical or drugs

causes for Hep A

ingestion of contaminated food or water

fecal oral route

risk factors of Hep A

weak immune system

unsanitary conditions

institutionalization

foreign travel to countries

illicit parenteral drug use

patho of hep A

•HAV viral replication occur in hepatocytes

•Viral RNA is converted into DNA by polymerase enzymes

•Viral proteins are made

•Viral particles excreted in feces

•After exposure IgM can be detected in blood

•After acute illness, IgG remains & creates immunity

Hep A s/s

•Flulike symptoms

•Hepatomegaly, Jaundice, Abdominal pain

•Dark urine, pruritus, Pale stool (steatorrhea)

•Smokers lose taste for tobacco 

Diagnosis of Hep A

•Liver enzymes (rise after first 4 weeks)

•Diagnosis usually based on antibodies IgM anti-HAV & IgG

Treatment for HAV

•Supportive: rest, good nutrition

•Avoid alcohol, acetaminophen

•HAV vaccine

•Close contacts can receive HAV Ig

Hep B causes

blood products and sexual contact

risk factors of Hep B

•African Americans, Cocaine use, High # sexual partners and/or unprotected sex, STI, HIV +, Handling blood products, IV drug use, MSM, Household contact with someone with HBV, Hemodialysis 

Hep B patho

•HBV produces viral proteins in the hepatocyte. It does not kill the cell but the immune system attacks when viral antigens are encountered.

• CD4 & CD8 cells respond to antigens on the cell surface.

•Chronic disease may lead to cirrhosis & hepatocellular carcinoma (HCC)

Hep B 4 stages

incubation

inflammatory reaction

immune reaction

antibodies produced

incubation period of Hep B

no s/s but can be passed to others.2-4 weeks

inflammatory reaction

flu like symptoms and jaundice

antigens/

HBV DNA detectable

LFT rise

3-4 weeks

immune reaction

immune system reacts

viral replication slows

HBV DNA lower/ undetectable

LFT decrease

stage 4

virus cannot be detected and antibodies produced

Hep B s/s

•Flulike symptoms, anorexia, RUQ/Epigastric pain

•Jaundice, Pruritus, Dark urine, light colored stools

•Hepatomegaly, splenomegaly, lymphadenopathy, spider angiogma, palmar erythema

•Severe cases: hepatic encephalopathy

diagnosis of Hep B- main one

presence of HBsAg in blood

what else is diagnostic for Hep B

IgG and IgM

increased liver enzymes and bilirubin levels

decreased albumin, PT, and co ag factors

what is key for preventing HBV

HBV vaccine

Hep C causes

blood and can mutate

risk factors of Hep C

•IVDA, Healthcare Providers, Nosocomial, Tattooing, Sharing razors, Acupuncture, HIV

patho of Hep C

•HCV incubation period 2 weeks – 8 months

•RNA polymerase, enzyme for HCV replication allows for inaccurate copying of the virus – this causes mutations.

•Strong response by cytotoxic T lymphocytes & helper T cells

•Acute Hepatitis C becomes chronic in 70%

Hep C s/s

•Flulike illness

•Jaundice, Anorexia, Weight loss

•Hepatomegaly, Splenomegaly, RUQ pain

•Dark urine, Steatorrhea

main diagnosis of Hep C

immunoblot assay

treatment of Hep C

antiviral meds

there is no vaccine

hep d

Defective RNA virus requires helper function of HBV for its replication, expression & duration

Parental drug use or sexual contact

Hep E

uSimilar to HAV, oral-fecal route

Chronic hepatitis

more than 6 months

chronic hepatitis increases risk of

cirrhosis

cancer of the liver

autoimmune hepatitis/ idiopathic hepatitis

No virus or toxic agents

Cell mediated attack of hepatic tissue

Responds well to immunosuppressive agents

NAFLD

nonalcoholic fatty liver disease

NAFLD is one of the most common causes of

chronic liver disease

NAFLD etiology

unknown but hepatocytes accumulate triglycerides

risk factors of NAFLD

obesity

metabolic syndrome

DM

protein malnutrition

NAFLD drugs and disease

•Drugs: Tamoxifen, Methotrexate

•Diseases: Wilson Disease, Glycogen storage disease, galactosemia

patho of NAFLD

•Insulin normally enhances free fatty acid storage in adipose tissue

•In insulin resistance fat storage is shifted to nonadipose tissues, like the liver.

•STEATOSIS* – abnormal accumulation of lipids within a cell

NAFLD 2 hits

2hits: 

•1 – macro vesicular steatosis causes problems with uptake, synthesis, degradation, & secretion of fatty acids

•2 - Free radicals are released after mitochondrial damage causing second hit

NAFLD s/s

•Mild – no symptoms

•Fatigue, weakness, RUQ pain, spiderlike blood vessels, jaundice, ascites, ankle edema, mental confusion

diagnosis of NAFLD

liver biopsy

best treatment for NAFLD

weight loss

alcoholic liver disease etiology

•Risk depends on the amount of alcohol used

alcoholic liver disease patho

•Alcohol is toxic to hepatocytes

•Repeat damage leads to alcoholic liver disease

•Initial cellular change – Steatosis*

•Chronic alcohol inhibits oxidation of fatty acids in the liver

•Fat accumulates & disrupts organelles

•Disrupted mitochondria releases free radicals, leads to inflammation

•50% of alcoholic hepatitis progress to alcholic liver disease & cirrhosis

•Poor prognosis

Alcohol liver disease s/s Mild

•RUQ pain, nausea, malaise, low grade fever, jaundice, dark urine, Hepatomegaly with tenderness

alcohol liver disease severe

•hepatic encephalopathy, coagulation dysfunction, Jaundice, GI bleeding (hematemesis), Esophageal varices, Ascites

diagnosis of alcoholic liver disease

liver biopsy

elevated AST and ALT - alot

hyper- triglycerides, cholesterol, bilirubin

hypo-albumin

nutrition treatment for alcohol liver disease

•High protein, low fat, low sodium (unless encephalopathy)

•Vitamins: folate, thiamine, vitamin K

third most common cause of death

cirrhosis

main cause of cirrhosis

HCV

what other 2 things put you at risk for cirrhosis

alcoholic liver disease and NAFLD

cirrhosis causes the liver to undergo

structural changes and fail to function

stellate cells

compromise extracellular matrix of liver - becomes stimulated

how do stellate cells mess with the liver

•Create collagenous fibrous tissue – impairs hepatocytes

•Constrictive effect of portal venous system

•Increases liver density & changes liver (scared and misshapen)

portal hypertension - change in cirrhosis

•Increased resistance in portal vein

•Drains venous circulation of GI sytem

•In Cirrhosis – creates collateral branches to decrease pressure

•Progression causes backup of pressure. Veins become visible – Caput Medusa

decreased detoxification capacity - change in cirrhosis

•Drugs may accumulate to toxic levels

•Nitrogenous wastes accumulate> High Ammonia levels > Encephalopathy

decreased bile synthesis - change in cirrhosis

•Poor fat digestion – Steatorrhea

•Decreased stores of fat soluble vitamins (A,D,E,K)

decreased albumin synthesis - cirrhosis change

•Nutritional deficiency

•Decreased colloid oncotic pressure – causes ascites. Also, can cause pulmonary edema, pulmonary effusions

hyperbilirubinemia - changes in cirrhosis

•Causes Jaundice

•Kernicterus – Bilirubin Encephalopathy