Case 10 SAP Flashcards
Biliary dyskinesia
problem with emptying gallbladder
Cholelithiasis
gallstones
Biliary colic
sudden pain in RUQ due to gallstones, also known as symptomatic cholelithiasis. Colicky and in waves, typically after eating. Usually from obstruction of cystic duct
Cholecystitis
inflammation of gallbladder likely from obstruction in cystic duct. RUQ pain, positive Murphy’s sign, pain more constant than biliary colic. get fever, nausea etc.
Positive Murphy’s sign
pain on inspiration while palpating gallbladder
Cholangitis
inflammation of any bile duct. can be infective, obstructive, autoimmune, or malignant. Charcot’s triad or Reynold’s pentad (in severe cases)
Charcot’s triad
Cholangitis. RUQ pain, jaundice, fever.
Reynold’s pentad
RUQ pain, jaundice, fever, altered mental status, shock (low BP, tachycardia)
Gallbladder mucocele
dilation of gallbladder due to chronic obstruction of cystic duct
Risk factors for gallstones
Crohn’s, diabetes, diet high in triglycerides and refined carbohydrate, diet low in fibre, female gender, genetic and ethnic factors, increasing age, medications (somatostatin analogue octreotide, glucagon-like peptide-1 analogues, ceftriaxone), non-alcohol related fatty liver disease, obesity, prolonged fasting/weight loss, use of HRT.
Morphology of obstructive gallbladder disease
gallbladder becomes enlarged, distended, and red. Gallbladder walls thicken. Can exude pericholecystic fluid when inflamed. Necrosis from ischaemia can occur. Bile ducts dilated.
Cardinal symptoms of gallbladder disease
RUQ pain, shoulder blade pain, pain after fatty meal, fever, nausea, vomiting, heartburn, indigestion, excessive gas, tenderness in RUQ, Murphy’s sign. If stones in duct: jaundice, dark urine, pale faeces, itching
Cardinal symptoms of pancreatic disease
pain which radiates to the back, jaundice, dark urine and pale stool (cancer), nausea, vomiting, loss of appetite, fever, shock in acute pancreatitis, chronic fatigue, weight loss, diabetes.
Define pancreatitis
Inflammation of the pancreas. can be acute or chronic
describe acute pancreatitis
sudden onset in response to short-term injury leading to autodigestion by its own enzymes. limited impact on secretory function and no gross structural damage
types of acute pancreatitis
mild, moderate, and severe
mortality from severe pancreatitis
50%
describe chronic pancreatitis
chronic fibro-inflammatory disease resulting in progressive and irreversible damage to the pancreatic parenchyma. loss of exocrine and endocrine capacity, although this may take years to develop
Risk factors for acute pancreatitis
I GET SMASHED
Idiopathic
Gallstones
Ethanol
Trauma
Steroids
Malignancy/mumps (infection)
Autoimmune
Scorpion sting
Hypertriglyceridemia/hypercalcaemia
Endoscopic retrograde cholangiopancreatography
Drugs (thiazide diuretics, ACEis, statins etc.)
Top three causes of acute pancreatitis
idiopathic, gallstones, alcohol
Risk factors for chronic pancreatitis
Alcohol in 70-80% cases
Others include smoking, recurrent acute, chronic obstructive cases, genetic abnormalities, metabolic conditions (hypertriglyceridemia and hypercalcaemia)
Pathology of acute pancreatitis
inappropriate release and activation of pancreatic enzymes → damage to pancreatic tissue → acute inflammatory response triggered
What three events cause enzyme release in acute pancreatitis?
Duct obstruction, acinar cell injury, defective intracellular transport
Duct obstruction in acute pancreatitis
accumulation of enzyme rich fluid and increased pressure in interstitium, lipase accumulation leads to local fat necrosis → inflammatory response compromises local blood flow leading to ischaemia of acinar cells resulting in release of digestive enzymes
Acinar cell injury in acute pancreatitis
can cause autodigestion from release and activation of zymogens
Defective enzyme transport within acinar cells in acute pancreatitis
normally the enzymes and hydrolases are transported via different pathways, but in pancreatitis distension of the ducts disrupts membrane trafficking leading to fusion of granules and lysosomes causing digestive enzyme activation
How does repeated acute pancreatitis cause chronic pancreatitis? (LADS)
may lead to ductal dilatation due to high back pressure, stellate cells laying down fibrotic tissue causing ductal stenosis, atrophy of pancreatic tissue, and low flow through the duct facilitating calcium stone formation
How does alcohol cause chronic pancreatitis?
stimulation of acinar cells to release cytokines leading to an immune response, neutrophils release superoxide and proteases acting on pancreatic tissue. reactive oxygen species from oxidative metabolism of alcohol may overwhelm cell defences. Impact on cellular secretion leading to plug formation in the ducts causing an obstruction. Transient contraction of sphincter of Oddi causing duct obstruction
Morphology in mild acute pancreatitis
oedema from vascular permeability, focal areas of fat necrosis
Morphology in severe acute pancreatitis
necrosis of islets, ducts, and acinar cells, vascular injury leading to haemorrhage
Morphology in chronic pancreatitis
atrophy, fibrosis, deformation of large ducts, calcium carbonate deposits
Clinical presentation in acute pancreatitis
severe epigastric pain which can radiate through to the back, associated with nausea and vomiting. Pain relieved by leaning forwards, exacerbated by lying down. Other features include high temperature, tenderness and swelling of the abdomen, and tachycardia.
Clinical features in chronic pancreatitis
repeated episodes of epigastric pain - burning or shooting pain that lasts hours or days. eventually constant mild to moderate pain between bouts of severe pain. advanced - steatorrhea (foul-smelling, oily stools), diabetes, weight loss.
Risks for alcohol-related liver disease
alcohol consumption, drug misuse, overweight/obese, female sex, pre-existing liver condition, and genetics (alcohol dependence and problems processing alcohol often run in families)
Risk factors for non-alcoholic fatty liver disease
type 2 diabetes, insulin resistance, conditions that affect the use of insulin, underactive thyroid, hypertension, high cholesterol, metabolic syndromes, aged over 50, and smoker.
Describe fatty liver disease
build-up of fat inside the hepatocytes that leads to hepatomegaly.
Causes of fatty liver disease
alcoholic liver disease, NAFLD (obesity, type 2 diabetes, hypertension, hypercholesterolaemia), drugs, hep C, nutritional disorders, systemic disorder (IBD etc.), non-insulin related metabolic disorders (Wilson’s disease etc.), and small bowel diverticulosis with bacterial overgrowth
Describe alcoholic hepatitis
acute inflammation of the liver which causes death of hepatocytes and is often followed by permanent scarring
Four steps of NAFLD:
fatty liver (steatosis) –> non-alcoholic steatohepatitis (inflammation) –> fibrosis/cirrhosis –> cirrhosis –> potentially to cancer
Which steps of cirrhosis are reversible?
Fatty liver, inflammation, and fibrosis (with treatment like diet, exercise, weight loss, bariatric surgery)
Non-alcoholic steatohepatitis (NASH) morphology
evidence of cell injury/cytoskeletal disruption, cell death, and accompanying inflammation
NASH histopathology
ballooned hepatocytes – essential finding indicative of microtubular disruption, may contain Mallory-Denk bodies.
Necroinflammation and lobular inflammation from immune response.
Hepatic fibrosis – perivenular/pericellular which may be accompanied by portal and periportal fibrosis
Difference between NASH and NAFLD
NAFLD is just fat with no damage to the liver, NASH has damage to the liver itself
Acute liver failure/fulminant hepatitis
characterised by acute liver injury with hepatic encephalopathy and coagulopathy that occurs <26 weeks of initial liver injury in the absence of pre-existing liver disease
Hyperacute liver failure timescale
<7 days since injury
Acute liver failure timescale
7-21 days after injury
Subacute liver failure timescale
> 21 days and <26 weeks since injury
Causes of acute liver failure
ABCs
A = acetaminophen, hep A, autoimmune hepatitis, adenovirus, amanita phalloides (mushroom poisoning)
B = hep B, Budd-Chari syndrome
C = cryptogenic, hep C, cytomegalovirus
D = hep D, drugs (and toxins)
E = hep E, Epstein-Barr virus
F = fatty infiltration (acute fatty liver of pregnancy, Reye’s syndrome)
G = genetic e.g. Wilson disease
H = ), hypoperfusion (ischaemic hepatitis, sinusoidal obstruction syndrome, sepsis), haemolysis elevated liver enzymes low platelets (HELLP), herpes simplex, heat stroke, hepatectomy, hemophagocytic lymphohistiocytosis
Chronic liver failure
progressive deterioration of liver functions which follows years of insidious progressive liver disease, is most associated with cirrhosis
Acute-on-chronic liver failure
decompensation of the diseased liver by other diseases/conditions that place demands on the liver. In most cases, liver transplantation is the only hope for survival.
Morphology of liver failure
liver is initially enlarged by swelling and oedema related to inflammation, but as parenchyma is destroyed the liver shrinks dramatically. Hepatocellular necrosis
Initial clinical features of liver failure
fatigue, anorexia, nausea, vomiting, and jaundice.
More advanced clinical features of liver failure
coagulopathy, hepatorenal syndrome, portal hypertension
Hepatorenal syndrome
renal failure with liver failure with no cause for kidney failure, decreased urine output, increased BUN and creatinine
Portal hypertension
increase in pressure leading to resistance to portal blood flow, splenomegaly, anaemia, leukopenia, thrombocytopenia, portosystemic shunting, shunting from intestine into general circulation, hepatic encephalopathy, development of collateral channels, caput medusae, oesophageal varices, haemorrhoids, ascites, and spontaneous bacterial peritonitis
Cardinal symptoms of liver disease
abdominal pain, dark urine, pale faeces, pruritus (itch), nausea, vomiting, loss of appetite, chronic fatigue, encephalopathy (confusion)
Cardinal signs of liver disease
jaundice (colour comes from bilirubin), fever, hair loss, as well as compensated or decompensated signs
Signs of compensated liver failure
Xanthelasmas, parotid enlargement, spider naevi, gynaecomastia, small or large liver, splenomegaly, clubbing, duputren’s contracture, xanthomas, scratch marks, testicular atrophy, purpura, pigmented ulcers
Signs of decompensated liver failure
Neurological i.e. disorientation, drowsy –> coma, hepatic flap, fetor hepaticus, ascites, dilated veins on abdomen, oedma
Dupuytren’s contracture
thickening and shortening of palmar fascia that leads to flexion deformities of the fingers. (benediction sign)
Palmar erythema
exaggerations of normal speckled mottling of the palm due to altered sex hormone metabolism leading to hyperoestrogenaemia
Spider naevi
vascular lesions consisting of a central arteriole surrounded by many smaller vessels due to an increase in oestrogen
Hepatic encephalopathy
occurs when toxins that are normally cleared from the body by the liver accumulate in the blood, eventually travelling to the brain. Ranges from subtle behavioural abnormalities, marked confusion and stupor to deep coma and death. Develops over days, weeks to a few months. Neurological signs include rigidity, hyperreflexia, and asterixis.
Precipitations of hepatic encephalopathy
alcohol, excess dietary protein, constipation, GI bleeding, and infection
Define cirrhosis
build-up of scar tissue in the liver that stops it from functioning properly. Insult to the liver can lead to inflammation or death of the hepatocytes. Inflammation then causes death of the hepatocytes and scarring, and the scarring leads to a fibrotic, nodular liver. Death of hepatocytes leads to regeneration of hepatocytes which in turn leads to a fibrotic, nodular liver.
Compensated cirrhosis
fibrosis present but liver functions also present, asymptomatic over many years, or symptoms are non-specific
Decompensated cirrhosis
liver cannot function properly, more severe symptoms like jaundice, ascites, GI bleeding, and hepatic encephalopathy
What can cirrhosis lead to? (Symptoms and diseases)
Portal hypertension, ascites, hypersplenism, oesophageal varices, synthetic dysfunction (coagulopathy, hypoalbuminemia), hepatorenal syndrome, hepatopulmonary syndrome, encephalopathy, hepatocellular carcinoma
Three main morphological features of cirrhosis
bridging fibrous septa, parenchymal nodule formation, disruption of architecture of entire liver
Stages of liver fibrosis histology
1 and 2 around central veins, 3 is bridging fibrosis, 4 is cirrhosis
Most common causes of cirrhosis in developed countries (top 3)
Alcoholic liver disease, fatty liver disease, chronic viral hepatitis (hep C)
Other causes of cirrhosis
autoimmune hepatitis, biliary diseases, genetic and metabolic liver disease, vascular disease, drugs and toxins, systemic diseases, idiopathic causes, developmental abnormalities, and infections
Unusual causes of cirrhosis
hereditary haemochromatosis, alpha-1 antitrypsin deficiency, Wilson’s disease, primary sclerosing cholangitis, and primary biliary cholangitis.
Hereditary haemochromatosis
Iron overload with deposition in liver, pancreas, heart, joints etc. Can cause hepatomegaly
Alpha-1 antitrypsin deficiency (liver)
Pulmonary emphysema and liver disease
Wilson’s disease
copper overload in liver, eye, and brain
Primary sclerosing cholangitis
bile ducts decrease in size due to inflammation and fibrosis, associated with chronic ulcerative colitis
Primary biliary cholangitis
bile ducts become injured, inflamed, and eventually destroyed
Hepatitis
inflammation of the liver
What does hepatitis look like histologically?
Pattern of liver injury characterised by portal and lobular inflammation with or without necrosis, depending on severity
Acute hepatitis
Duration of less than six months. Three possible pathways: resolution, chronic hepatitis, or hepatic failure
Causes of hepatitis
Infection, autoimmune, drug induced liver injury
Hepatotropic hepatitis
Inflammation to the liver only
Causes acute hepatotropic hepatitis
hep A and hep E via oral route
Causes chronic hepatotropic hepatitis
hep B, C, and D via the blood rout
Non-hepatotropic hepatitis
systemic with liver involvement
Causes acute non-hepatotropic hepatitis
Epstein-Barr virus, cytomegalovirus, herpes simplex virus
What test is diagnostic for acute pancreatitis?
Serum amylase or lipase 3x normal upper limit
