PBL 2 Flashcards
what’s the commonest cause of chronic liver disease?
alcohol
whats more of a risk factor for liver disease, binge drinking or daily drinking?
daily drinking
whos more likely to get liver disease, men or women?
women are more likely to get more severe disease e.g. alcoholic liver disease
men are more likely to die from cirrhosis
what are the 3 stages of alcoholic liver disease?
alcoholic fatty liver (steatosis)
alcoholic hepatitis (steatohepatitis)
cirrhosis
outline the pathophysiology of alcoholic steatosis?
alcohol enters hepatocytes
Alcohol dehydrogenase converts alcohol to acetaldehyde and acetaldehyde dehydrogenase converts acetaldehyde to acetate. Both of these mechanisms work by also converting NAD+ to NADH; as NADH levels increase, the cell starts to produce more fatty acids and lower NAD+ levels result in less fatty acid oxidation.
acetaldehyde also promotes production of enzymes involved in fatty acid synthesis and inhibits enzymes involved with fat oxidation. Both of these lead to more fat production in the liver (fatty change / steatosis).
what pathway does chronic alcohol use up-regulate?
whats the effect of this?
which patients is this effect exaggerated in?
the CYP450 2E1 pathway (enzyme involved in ethanol metabolism)
this produces harmful reactive oxygen species which damage protein and DNA
this effect is exaggerated in patients with deficient antioxidants e.g. those who are malnourished
outline the pathophysiology of alcoholic steatohepatitis?
Chronic alcohol exposure activates hepatic macrophages, triggering inflammation
Acetaldehyde can also bind to cellular proteins of the hepatocyte (acetaldehyde adducts). The immune system recognises these as foreign so neutrophils destroy hepatocytes - promoting inflammation.
As cells become inflamed and damaged, it is now referred to as steatohepatitis.
what would you see on histology at alcoholic steatohepatitis stage?
mallory bodies (cytoplasmic hyaline inclusions of hepatocytes)
what would be the symptoms at alcohol steatosis stage?
mostly asymptomatic
how would alcoholic steatohepatitis present?
painful hepatomegaly neutrophil leukocytosis ALT and AST levels raised ALP and GGT elevated thrombocytopenia hypoglycaemia
what is ALT?
alanine transaminase
liver enzyme released into the blood when hepatocytes are damaged
what is AST?
aspartate aminotransferase
liver enzyme released into the blood when hepatocytes are damaged
what is ALP?
Alkaline phosphatase
an enzyme made in liver cells
what is GGT?
gamma-glutamyl transferase
mostly found in the liver
outline the cirrhosis stage of alcoholic hepatitis?
◦ chronic inflammation and subsequent attempts at tissue repair lead to formation of scar tissue. As a result the livers internal structure is disrupted, impairing its functions.
why does cirrhosis cause portal hypertension?
When an obstruction (in this case fibrous tissue) prevents blood flow, venous blood accumulates in the portal system and pressure rises >12mmHg
why can cirrhosis cause hepatic encephalopathy?
As liver functions decline, toxins can build up and reach the general circulation and pass into the brain producing symptoms such as confusion, drowsiness, tremor or even coma
whats the treatment for alcoholic hepatitis?
abstinence
corticosteroids to suppress the immune system
liver transplantation
what is the portal venous system?
the vessels involved in the drainage of the GI tract and spleen into the liver
portal vein, splenic vein and mesenteric vein
what are the 3 connections between the portal venous system and systemic venous system?
oesophagus
superior portion of anal canal
round ligament of liver
what are portosystemic shunts?
when blood is diverted away from the portal system and backs up into systemic veins
Portal hypertension causes less blood to reach the liver. What is the effect of this?
decreased liver function and blood detoxification (presents as jaundice). Build up of toxic metabolites in the blood that can cause hepatic encephalopathy
whats the effect of portosystemic shunts caused by portal hypertension?
oesophageal varices which can rupture and cause haematemesis
haemorrhoids in the rectum which can bleed and present as melena or Hematochezia
caput medusae
what is caput medusae?
a cluster of swollen veins in your abdomen
why can portal hypertension cause caput medusae?
portosystemic shunts cause the round ligament to rechannel so the blood from the portal system passes into the systemic veins of the abdomen which have to dilate
why can portal hypertension lead to anaemia, leukopenia and thrombocytopenia?
blood backs up to the spleen causing congestive splenomegaly which causes hypersplenism, trapping RBC, WBC and platelets
why can portal hypertension cause ascites?
• Endothelial cells lining blood vessels release more NO = peripheral arteries dilate = bp drops = stimulates release of aldosterone which tries to bring bp back up by getting the kidneys to retain more sodium and water = plasma volume expands so much that fluid gets pushed across tissues into the peritoneal cavity
whats an example of a pre-hepatic portal hypertension cause?
portal vein obstruction
whats an example of a intrahepatic portal hypertension cause?
cirrhosis
schistomiasis
sarcoidosis
whats an example of a post-hepatic portal hypertension cause?
right sided heart failure
constrictive pericarditis
budd chiari syndrome
what is Budd chairi syndrome?
a condition in which the hepatic veins are blocked or narrowed by a thrombus. This blockage causes blood to back up into the liver, and as a result, the liver grows larger
what are alcoholics deficient in?
folate vitamin B6 vitamin B1 vitamin A calcium, magnesium, iron and zinc
what are the classical blood work findings in alcoholics?
low RBC, WBC, platelets, albumin, Hb, haematocrit, blood sugar
raised MCV, MCH, AST, ALT, GGT, prothrombin time and activated partial thromboplastin time
what are some social implications of alcohol?
family break up divorce domestic abuse unemployment homelessness financial struggles poor work performance workplace accidents violence traffic fatalaties
what is first pass metabolism?
when a drug is metabolised by the liver before reaching the systemic circulation.
what enzyme is important for drug metabolism?
CYP450
why are highly protein bound drugs like phenytoin and prednisolone so dangerous in patients with severe liver disease?
because the hypoalbuminaemia is associated with reduces protein binding and increased toxicity
why are oral anticoagulant drugs like warfarin sodium so dangerous in patients with severe liver disease?
because the reduced hepatic synthesis of blood clotting factors increases the sensitivity to them
why are NSAIDs and corticosteroids contraindicated in severe liver disease?
they cause fluid retention and so exacerbates oedema and ascites
whats the pathophysiology of acute pancreatitis?
a cause -> pancreatic tissue becomes inflamed which damages the acinar cells so they release their digestive enzymes (proteases, amylase, lipase), resulting in further damage to surrounding structures. Proteases causes damage to cells and vasculature. Destruction from proteases and the inflammatory response can cause leaky blood vessels that can rupture; all the extra fluid causes the capsule of the pancreas to swell. These leaky vessels can cause tissue oedema and inflammation. .
Amylase levels increase in the blood. Lipases increase in the blood and can result in fatty necrosis of the pancreas - these increased lipase levels cause the released fatty acids to bind Ca2+ forming a white precipitate in the necrotic fat - if this is very severe it can cause hypocalcaemia
how does hypocalcaemia present?
with tetany
what is Cullens sign?
bruising around the periumbilical region
what is grey turners sign?
bruising along the flank of the body
what are some outcomes of acute pancreatitis?
chronic pancreatitits pancreatic ascites abscesses pseudocysts diabetes haemorrhage acute respiratory distress syndrome fistula between pancreas and parietal pleura of lungs (pancreatic effusion) acute renal failure death
whats the biggest cause of chronic pancreatitis?
alcohol
whats the pathophysiology of chronic pancreatitis?
acute pancreatitis ongoing leads to atrophy of the acinar tissue and fibrosis (layed down by stellate cells) with relative preservation of islets. Increased concentration of pancreatic juice proteins and increased duct pressure precipitates formation of protein plugs with calcium carbonate, leading to calculi.
why does chronic pancreatitis cause steatorrhoea?
lack of lipases in advanced disease and acinar cells being impaired results in malabsorption of fat
why is diabetes mellitus a long term complication of chronic pancreatitis?
the inflammation destroys alpha and beta pancreatic cells eventually
what is peritonitis?
inflammation of the peritoneum
what is secondary peritonitis?
if there is a cause e.g. ruptured appendix, perforated colon, stomach ulcer
where is the GI tract perforation if paracentesis shows gram negative bacteria in peritonitis?
and gram positive?
distal GI tract
proximal GI tract
what is spontaneous peritonitis?
if infection arises from fluid build up in abdominal cavity e.g. bacterial migration from GI lumen which is more common with ascites/cirrhosis
which microorganisms most commonly cause spontaneous peritonitis?
gram-negative Escherichia coli and Klebsiella pneumoniae and gram-positive Streptococcus pneumoniae
what are risk factors for peritonitis?
previous history of peritonitis, alcohol use, weak immune system, fluid accumulation in abdomen, liver disease
what are symptoms of peritonitis?
fever and chills, abdominal pain and tenderness, abdominal bloating, abdominal distention, nausea, vomiting, diarrhoea, minimal urine output, excessive thirst, fatigue, constipation
rebound tenderness
how do we diagnose peritonitis?
blood tests for high WCC, imaging e.g. xray to check for gastric perforation, peritoneal fluid analysis (paracentesis)
how do we treat peritonitis?
determine underlying cause, antibiotics via IV , surgical treatment to remove infected tissue
what antibiotics are usually given for peritonitis?
beta lactams
cephalosporins
quinolones
what are some complications of peritonitis?
dehydration sepsis multi organ failure hepatic encephalopathy hepatorenal syndrome shock death
what is hepatorenal syndrome?
Impaired kidney function that occurs in individuals with advanced liver disease.
in liver failure/portal hypertension aldosterone tries to raise bp by getting the kidneys to retain Na+ and water = when this happens over a long period of time we get renal vasoconstriction and reduced blood flow = eventually leading to renal failure
