Gastrointestinal 2 Flashcards
functions of the liver
- Synthesis: Of albumin, growth factors, urea, coagulation factors, complement, c-reactive protein, specific binding proteins (iron, copper, vitamin A). Excretes bilirubin from RBC turnover.
- Storage: Of vitamins, glycogen, and lipids. Controls the absorption and transport of lipids (bile salts and lipoproteins)
- Metabolism: Biotransformation, Metabolizes amino acids, Regulates hormones: insulin, thyroxin, androgen, estrogen.
- Regulates blood glucose.
what characterized non-alcoholic fatty liver disease?
excess lipid accumulation in the liver.
frequency of non-alcoholic liver disease
40% in developed countries
NAFLD is a major complication of ______ and _______
obesity and insulin resistance
what can non-alcoholic fatty liver disease progress to?
- Progresses to NASH – Non-Alcoholic Steatohepatitis
(Now is fat plus inflammation and scarring.) - Cirrhosis (is a non-alcoholic cause of this)
- Which can then cause/develop into liver failure or hepatocellular carcinoma
are there drugs available for NAFLD?
no but it is preventable and partially reversible
components in the pathogenesis of NAFLD?
- Excess fatty acids in liver: from diet + adipose tissue +lipogenesis > metabolism + secretion
- Adipose tissue releases inflammatory adipokines like leptin that promote steatosis and fibrosis.
(Release many pro-inflammatory that have a predominant effect on the liver.) - Liver releases hepatokines that promote lipid accumulation and inflammation.
- Obesity alters intestinal microbiome and increases permeability: bacteria enter portal blood.
- Kupffer cells activate, release cytokines, initiate inflammation.
- Stellate cells activate, initiate fibrosis – so scarring in the liver.
forms of bilirubin
- Bilirubin from normal turnover or RBCs is not water soluble and is bound to albumin for transport.
- Liver conjugates bilirubin to water-soluble glucuronides which are excreted in the bile.
what is jaundice?
- Excess plasma level of either form of bilirubin can lead to tissue deposition: jaundice.
o Yellow sclera is an obvious indicator – useful for someone with dark skin since melanin can mask the yellow in the skin.
when does hemolytic jaundice occur?
- Occurs when there is a lot of bleeding.
- liver overloaded, so excess of unconjugated bilirubin, which is not water soluble.
what happens in extrahepatic biliary obstruction?
- excess of conjugated bilirubin, which is water soluble, so can be excreted in urine.
- Intestinal bacteria normally convert a small fraction of the conjugated bilirubin to a brown pigment; so, obstruction can produce colorless stool – cannot go from the liver to the intestine.
what can cause the obstruction in extrahepatic biliary obstruction?
o Congenital biliary atresia: born with a section that is not open.
o Stone
o Tumor that is compressing it
o Enlargement of a lymph node
therapy for extrahepatic biliary obstruction
- Bile duct obstruction requires surgical correction.
what is gilbert’s syndrome and what is the prevalence?
- intermittent jaundice due to reduced transcription glucuronyl transferase (UGT)
(mutation in the promoter region of the UGT gene. still works but doesn’t work as well – high stress can trigger it.) - Up to 10% of the population,
- symptom onset in early adulthood
o more common in males. - harmless
how does neonatal jaundice occur and what is the therapy?
- newborn often have increased RBC hemolysis + lower synthesis of liver enzymes and albumin (still immature) + immature BBB,
- which allows free bilirubin to enter the brain with deposition in the basal ganglia and neuronal degeneration: Kernicterus.
(Causes neurodegeneration in the basal ganglia – neural necrosis.) - Prevented by treatment with blue light: photoconversion of bilirubin to a soluble derivative.
incubation period for hepatitis?
weeks – months between exposure and illness.
symptoms of viral hepatitis
o symptoms usually include fatigue, weakness, GI problems (nausea, vomiting, diarrhea, loss of appetite)
o may include fever, jaundice, and dark urine.
o B, C, and D can also cause skin rash, weight loss, joint pain, loss of inclination to smoke.
Hepatitis viruses are very small so can squeeze through the ____________
sinusoid in the liver
viral hepatitis is a risk factor for _____
HCC
transmission of hepatitis A
- Transmission fecal-oral.
- Easily crosses intestine, so gets in the blood, liver, bile, and then stool, which can go in the water and contaminate it.
- Common in situations with poor hygiene, easily spread.
progression of hepatitis A
Don’t have the capacity to cause a chronic disease.
therapy for hepatitis A
vaccine for travel
symptoms for hepatitis A
usually mild, usually fatigue, GI problems, fever.
Due to the immune response in the liver but it can be resolved.
transmission of hepatitis B
- Highly contagious; virus in blood and all body fluids
- Major spread through sexual activity.
life cycle and effect of hepatitis B
- Viral reproduction makes new virions plus non-infectious particles with only surface antigens, used as a “decoy” against the immune system.
- Immune response, both innate and adaptive, causes liver injury—immune reaction destroys hepatocytes to stop the spread of the virus.
- 90% of people recover.
what happens when infants get hepatitis B
have lower immune defense and fewer symptoms, but most become carriers.
progression of hepatitis B
- Can cause acute liver failure.
- Chronic infection is a major risk for cirrhosis and liver carcinoma.
- 10% become chronic asymptomatic carriers who spread disease and who often progress to cirrhosis.
- Primary liver disease almost always caused by this virus.
therapy for hepatitis B
- Vaccination is now universal in Canadian children; but infection is still widespread in poor countries.
- 3 injections during 6 months (usually done in grade 4 in Canada)
transmission of hepatitis C
Main route of transmission currently is IV drug use but can also be spread sexually.
progression/life cycle of hepatitis C
- Majority progress to chronic disease with eventual cirrhosis (20% of people with chronic disease will progress) and significant risk of carcinoma.
- Increase in monocytes, fibrosis, and necrosis.
- Virus enters hepatocyte by attachment to CD81 and SRB1 (scavenger receptor) on cell surface, then is endocytosed.
- Virus reproduces in ER of hepatocyte, then attaches to a protective lipoprotein, makes a lipoviralparticle.
- Thought to protect it against immune system.
- Also helps it to easily be transported into the blood.
- It hijacks the hepatocyte synthesis of lipoproteins.
therapy for hepatitis C
- Previous therapy was toxic with low success rate.
- Ability to now cure Hepatitis C (block reproduction) – need for liver transplant shifting to cirrhosis and cancer from NASH instead of Hepatitis C.
transmission of hepatitis D
- Transmitted by bodily fluids.
progression/life cycle of hepatitis D
- Delta virus.
- Requires Hepatitis B to produce the viral envelope.
- Requires its surface envelopes (takes the non-infectious particles).
- Superinfection produces severe symptoms: Causes the most severe chronic hepatitis due to greater immune response, leading to extensive necrosis
therapy for hepatitis D
- No cure.
- Prevention: immunize against hepatitis B
transmission of hepatitis E
- Transmission fecal-oral.
o Epidemics in poor countries – contamination in water.
most common subtypes of hepatitis E
- HEV 1 and 2 subtypes are the most common.
effect of hepatitis E
- Recovery is the major outcome.
- Many are asymptomatic.
- Linked to neurological syndromes in a small fraction of patients.
- High risk in pregnancy: 20-30% death.
- Don’t have the capacity to cause a chronic disease.
what does chole mean?
bile
what does cystis mean?
bladder
what does dochos mean?
duct
what does lithos mean?
stone
what are gallstones and the types?
- Ingredients in bile may precipitate within the gallbladder, producing stones.
- Composed of pigment (bilirubin salts), cholesterol, or a mixture.
- There are two major types: pigment and cholesterol gallstones. (Most are cholesterol (80%))
gallstones are related/caused by ____
low fiber and high fat diet
risks of gallstones
obesity, rapid weight loss, and chronic hemolysis
what causes the pain of gallstones
related to irritation of gallbladder or progression through the bile duct
treatment of gallstones
- often surgical – laparoscopic cholecystectomy (take gallbladder out).
- Another strategy is to try to dissolve the stone with shock waves
potential complications of gallstones
- Acute cholecystitis:
inflammation of gallbladder following obstruction, can cause obstructive jaundice., may be accompanied by infection. Elevated pressure may relocate the stone.
Risk for abscess, perforation, peritonitis. Reversible with surgical correction. - Choledocholithiasis (“bile/duct/stone”): causes cholestasis, (“bile/stops flowing”) and obstructive jaundice.
- Ulceration of gall bladder, fistula to duodenum.
- Pancreatitis, intestinal obstruction
