liver Flashcards
Liver Failure: define acute and chronic hepatic failure
acute
- Acute live injury
- with encephalopathy and deranged coagulation (INR > 1.5)
- in a patient with a previously normal liver
- <26 weeks in normal healthy person
chronic
on background of cirrhosis
Liver Failure: aetiology?
- Infection e.g. viral hepatitis B, C.
- Induced e.g. alcohol, drug toxicity,
- Paracetamol - COMMON CAUSE
- Alcohol
- Anti-depressant - Amitriptyline
- NSAIDs
- Ecstasy or cocaine
- Antibiotics - Ciprofloxacin, doxycycline or erythromycin - Inherited e.g. autoimmune.
- Hepatocellular carcinoma
One big complication of liver failure?
and why?
Hepatic Encephalopathy ]
The liver can’t get rid of ammonia and so ammonia crosses the BBB -> cerebral oedema.
Liver Failure: Complications>
- Hepatic encephalopathy.
- Abnormal bleeding.
- Jaundice.
- Ascites.
Liver Failure: management>
- Treat cause
eg paracetamol poisoning - give N-acetyl cysteine
2. Treat complications (Ascites – diuretics, cerebral oedema – mannitol, bleeding – vit K + fresh frozen plasma, encephalopathy – lactulose, sepsis – sepsis 6,antibiotics, hypoglycaemia - dextrose)
- . Mineral supplements e.g. calcium, potassium, phosphate etc.
- Liver transplant.
Liver Failure: signs and symptoms?
Hepatic encephalopathy: so also (altered mood/dyspraxia, liver flap/asterixis)
- Abnormal bleeding (coagulopathy)
- Ascites
- Jaundice
- small liver
- fetor hepaticus (sweet/pear drops and musty breath/urine)
- cerebral oedema
Symptoms:
- Same as acute presentation (malaise, myalgia, fever), restless, altered personality
Alcoholic Liver Disease: Stepwise progression of alcoholic liver disease?
and the Pathophysiology?
- Alcohol related fatty liver: hepatocytes contain triglycerides.
- Alcohol hepatitis.
- Alcoholic cirrhosis: destruction of liver architecture and fibrosis.
healthy liver → simple steatosis (beginning of fatty liver disease) → steatohepatitis (fatty liver disease) → cirrhosis
Alcoholic Liver Disease: histological signs?
Signs and symptoms?
HISTOLOGY
Neutrophils and fat accumulation within hepatocytes.
- Perivenular fibrosis - scar tissue forms around central veins
- Dense cytoplasmic inclusions called Mallory bodies are sometimes seen in hepatocytes and giant mitochondria are also a feature
SIGNS:
vague abdominal signs —> n+v, diarrhoea
- signs: mild jaundice, ascites, hepatomegaly, iron overload
MACROCYTIC ANAEMIA - symptoms: fatigue, malaise, dull RUQ pain
Alcoholic Liver Disease: investigations?
- GGT very raised (gamma-glutamyl transferase)
- AST and ALT may be mildly raised
- ALP (alkaline phosphate) raised
- prothrombin time raised
- low platelet count
- low blood sugar
- FBC – Macrocytic anaemia!!!!
- Liver Biopsy !!!
- Perivenular fibrosis - scar tissue forms around central veins
- Dense cytoplasmic inclusions called Mallory bodies are sometimes seen in hepatocytes and giant mitochondria are also a feature
- ultrasound or CT = fatty infiltration as will liver histology
Alcoholic Liver Disease: management?
- Drinking cessation
- Treat delirium tremens* (withdrawal symptom) **with DIAZEPAM
- IV Thiamine. - to prevent Wernicke-Korsakoff encephalopathy (presents with ataxia, confusion and nystagmus) which occurs from alcohol withdrawal, occurs 6-24 hours after last drink and lasts up to a week
- Diet changes (high in vitamins and proteins) and consider *corticosteroids** for inflammation/to suppress immune system
- Avoid aspirin and NSAIDs
- Liver transplant if very severe
For fatty liver - if pt stops alcohol = fat will disappear and return to normal
Non-alcoholic Liver Disease: define and progression?
Disease due to fat accumulation in the liver and associated with inflammation AND associated w
“metabolic syndromes”
- Steatosis
- Steatohepatitis - baso when you have steatosis and inflammation (NASH) in the absence of alcohol
- Fibrosis
- Cirrhosis - non reversible end stage of progressive chronic liver disease
Non-alcoholic liver disease: aetiology?
Risk factors?
Usually affects individuals with metabolic syndrome: (3/5)
- Type 2 diabetes mellitus.
- Hypertension.
- Obesity.
- Hyperlipidaemia
- Hypertriglyceridaemia
Overweight diabetics with high cholesterol!
RISK FACTORS: inc >50, high BMI, DM, HYN, hyperlipidaemia, excessive soft drinks
Non-alcoholic Liver disease: Pathophysiology w ref to insulin resistance and the diff diseases:
(insulin resistance) = play a role → insulin receptors become less responsive to insulin THUS liver increases fatty acid storage and decreases fatty acid oxidation THUS also decreased secretion of fatty acids into bloodstream and increased synthesis and uptake of fatty acids = steatosis = liver = large, yellow, soft and greasy
= Steatosis!!!!!
Steatohepatitis!!!!
When you have steatosis and inflammation - damage attracts neutrophils to liver (inflammation) = MALLORY bodies!!
Fibrosis:!!
Steatosis and inflammation and fibrosis - baso when stellate cells lay down fibrotic tissue = fibrosis
Baso the stellate cells release cytokines which attract neutrophils and macrophages SO inflammation -> necrosis -> eventual fibrosis
Cirrhosis: see cirrhosis cards
non-alcoholic liver disease: signs and symptoms ?
- even at advanced stages = may be no symptoms
- Often vague symptoms - fatigue, malaise, RUQ discomfort (‘gnawing’)
Once there is significant damage:
- hepatomegaly
- Pain
- Jaundice
- Accumulation of fluid in the peritoneal cavity = ascites
non-alcoholic liver disease: investigations?
Increase in:
- ALT (alanine transaminase)
- AST (aspartate transaminase) SOMETIMES
(In alcoholic - its opp so big rise in AST and less of a rise in ALT)
- ultrasound, MRI, CT scan = look for fatty infiltration
- Biopsy = to diagnose disease - >5% fat content = abnormal
- (raised IgM)
Cirrhosis: define?
Non-reversible
end stage of all progressive chronic liver diseases; which once fully developed is irreversible and may be associated clinically with symptoms and signs of liver failure and portal hypertension
Or
A chronic disease of the liver resulting from necrosis of liver cells followed by fibrosis. The end result is impairment of hepatocyte function and distortion of liver architecture.
Cirrhosis: aetiology
- Alcohol!
- Hepatitis B and C.
- Any chronic liver disease e.g. autoimmune, metabolic, vascular etc.
Cirrhosis: management?
- Deal with the underlying cause e.g. stop drinking alcohol.
- Screening for HCC.
- Consider transplant.
Cirrhosis: complications?
Commonest serious infection in those w cirrhosis = spontaneous bacterial peritonitis!!!!!!!
(can also affect immunocompromised people and those undergoing peritoneal dialysis)
- neoplasia
- ascites
- HCC
- coagulopathy (fall in clotting factors 2,7,9,10)
Cirrhosis: Pathophysiology?
Liver injury causes necrosis and apoptosis, releasing cell contents and reactive oxygen species (ROS)
- This activates hepatic stellate cells and tissue macrophages (Kupffer cells)
- Stellate cells release cytokines that attract neutrophils and macrophages to the liver which results in further inflammation and thus necrosis and eventual fibrosis
- Kupffer cells phagocytose necrotic and apoptotic cells and secrete pro- inflammatory mediators: TGF-beta and PDGF
- → Increased myofibroblasts leads to progressive collagen matrix deposition resulting in fibrosis and scar accumulation in the liver
Chronic Hepatitis: aetiology?
Acute Hepatitis: aetiology?
Non-infective causes of acute and chronic hepatitis??
CHRONIC Infective causes: - 1. Hepatitis B (+/-D). 2. Hepatits C. 3. Hepatitis E.
Non-infective causes:
- Alcohol
- Drugs
- Autoimmune
- Hereditary metabolic
ACUTE: Viral: - Hepatitis A and E • Herpes viruses e.g. EBV (Epstein Barr Virus), CMV (Cytomegalovirus), VZV (Varicella Zoster Virus) Non-viral: • Leptospirosis • Toxoplasmosis • Coxiella (Q fever)
Non-infective causes:
- Alcohol
- Drugs
- Toxins/poisoning
- Pregnancy
- Autoimmune
- Hereditary metabolic
Non-infective causes are baso:
- Alcohol.
- Drugs.
- Toxins.
- Autoimmune.
Acute vs Chronic Hepatitis: define?
Acute:
Acute hepatitis is defined as hepatitis within 6 months of onset
Chronic:
Chronic hepatitis is defined an any hepatitis lasting for 6 months or longer
Acute Hepatitis: symptoms and signs?
- General malaise.
- Myalgia.
- GI upset.
- Abdominal pain.
- Raised AST, ALT.
- +/- jaundice.
- Tender hepatomegaly
- Abdominal pain - particularly in right upper quadrant
Viraemia causes patient to feel unwell, with non-specific symptoms that include nausea, fever, malaise
Hepatitis: (general) causes?
- Viral e.g. A, B, C, D, E.
- Drug induced.
- Alcohol induced.
- Autoimmune.
HAV: define and features?
incubation period?
risk factors?
RNA virus & ACUTE ONLY
Spread via the faeco-oral route
eg contaminated food/water, shellfish
INCUBATION PERIOD
Short incubation period of 2-6 weeks
RISK FACTORS
travellers and food handlers
HAV: investigations?
HAV IgM antibody = ACTIVE INFECTION(non-specific) production is in acute stage
HAV IgG antibody = RECOVERY OR VACCINATION
Raised serum AST or ALT
HAV: management?
- Supportive.
- Monitor liver function to ensure no fulminant hepatic failure.
- Manage close contacts.
HEV: define?
RNA virus
ACUTE HEPATITIS only
Usually self-limiting acute hepatitis: Can cause fulminant hepatitis
FAECAL-ORAL ROUTE (via seafood)
HEV: investigations?
Viral serology: Initially anti-HEV IgM and then anti-HEV IgG.
Serology is similar to Hepatitis A (HEV IgM = ACTIVE INECTION,
HEV IgG = RECOVERY)
Use HEV RNA to detect chronic infection
HEV: management?
- Good food hygiene.
- A vaccine is in development.
NO Vaccine available (only available in china!!!)
Prevention via good sanitation and hygiene
Once you’ve had Hep E then you cannot get infected again - 100% immunity
HBV: define?
DNA virus (it replicates in hepatocytes)!!
& ACUTE + CHRONIC HEPATITIS (chronic in 20% of cases)
HBV: aetiology / transmission?
Blood-borne transmission e.g. IVDU, needle-stick, sexual, MTCT.
HBV is highly infectious!
HBV: investigations?
Viral serology: HBV surface antigen can be detected from 6w - 3m or anti-HBV core IgM after 3 months.
HBV: management?
A - How would you know if an individual had been vaccinated against hepatitis B?
B - How long after infection with hepatitis B virus is anti-HBV core (IgM) present in the serum for?
C = How long after infection with hepatitis B virus is HBsAg present in the serum for?
D = How would you know if someone had acute or chronic HBV infection?
- Supportive.
- Monitor liver function.
- Manage contacts.
- Follow up at 6 months to see if HBV surface Ag has cleared. If present -> chronic hepatitis.
two treatment options for HBV infection.
- Alpha interferon - boosts immune system.
- Antivirals e.g. tenofovir. They inhibit viral replications.
A = If vacced —> They would have anti-HBVs IgG in their serum.
B = Anti-HBV core (IgM) slowly rises from 6 weeks after infection and its serum level peaks at about 4 months.
C = HBsAg will be present in the serum from 6 weeks - 3 months after infection.
D = You would do a follow up appointment at 6 months to see if HBV surface Ag had cleared. If it was still present then the person would have chronic hepatitis.
HDV: define?
Can’t exist wo?
I NCOMPLETE RNA VIRUS & ACUTE + CHRONIC HEPATITIS
-
REQUIRES HBV for assembly
Needs the HBV Sa to protect it
(Can result in HCC!!!!)
HDV: aetiology/transmission?
Blood-borne transmission, particularly IVDU.
HCV: define?
Aetiology/transmission?
- RNA FLAVIVIRUS
- & ACUTE + CHRONIC HEPATITIS
Blood-borne
HCV: risk factors?
- IVDU.
- People who have required blood products e.g. blood transfusion.
- Needle-stick injuries.
- Unprotected sexual intercourse.
- Materno-foetal transmission.
HCV: investigations?
You want to find out if someone has previously been infected with HCV. How could you do this?
Viral serology - HCV RNA tells you if the infection is still present.
HCV RNA:
• Indicates current infection
• Diagnoses acute infection GOLD STANDARD
HCV IgG = NOT DIAGNOSTIC
Ans——> Viral serology - anti-HCV IgM/IgG indicates that someone has either a current infection or a previous infection.
HCV: management?
And prevention?
Lots of new drugs have been developed recently for HCV infection. Direct acting antivirals (DAA) are currently in use e.g. NS5A and NS5B.
Prevention:
- Screen blood products.
- Lifestyle modification.
- Needle exchange.
There is currently no vaccination and previous infection does not confer immunity.
HCV: What percentage of people with acute HCV infection will progress onto chronic infection?
Approximately 70%.
Jaundice: urine/stools/itching/liver tests
in someone w pre-hepatic VS cholestatic (hepatic or post-hepatic) jaundice?
Pre-hepatic: Normal urine Normal stools NO itching Normal liver tests
BUT IN CHOLESTATIC (hepatic/post-hepatic) jaundice: Dark urine Pale stools MAYBE itching ABNORMAL liver tests
Pre-hepatic vs hepatic/post-hepatic jaundice:
Aetiology?
Pre-hepatic:
- Gilberts (deficiency in UDP Glucuronyl Transferase)
- Haemolysis
Hepatic: = baso LIVER DISEASE (see below) 1. Viral hepatitis. 2. Alcoholic hepatitis. 3. Drugs. (Hepatitis) 4. Cirrhosis. Ischaemia Neoplasm Congestion
Post-hepatic: baso BILE DUCT OBSTRUCTION:
- - Gall-stone:
- Bile duct
- Mirizzi syndrome (stone in gallbladder/cystic duct presses on
the common bile duct = jaundice)
- Stricture
- Blocked stent
Jaundice: symptoms?
- Biliary pain.
- Rigors - indicate an obstructive cause.
- Abdomen swelling.
- Weight loss.
Jaundice: define?
Yellow discolouration of the skin due to RAISED SERUM BILIRUBIN
Gallstones: risk factors?
- Female.
- Obese
- Fertile.
smoking
Gallstones: management?
Laproscopic cholecystectomy. - gallbladder removal
For pure or near-pure cholesterol stones = stone dissolution (these can be solubilised by increasing bile salt content of bile)
- Give ORAL URSODEOXYCHOLIC ACID (however these tend to reoccur so surgery is still preferred)
- Can also give cholesterol lowering agents such as statins e.g.
SIMVASTATIN
Shock wave lithotripsy:
- Shock wave directed on to gallbladder stones to turn them into
fragments so that they can be passed
- However the cystic duct requires patency for the fragments to pass
Gallstones: complications?
gb vs bile duct?
IF IN GB AND CYSTIC DUCT 1. Biliary pain./COLIC (- Acute cholecystitis - Empyema - gallbladder fills with pus - Carcinoma - Mirizzi’s syndrome - stone in gallbladder presses on bile duct casing jaundice - **In bile ducts:**)
IF IN BILE DUCTS
- Obstructive jaundice.
- Cholangitis (infection of the biliary tract).
- Pancreatitis.
gb:
- colic
- cholecystitis
- MAYBE obstructive jaundice (mirzzi)
- NO CHOLANGITIS
bile duct:
- colic
- NO cholecystitis
- yes obstructive jaundice
- CHOLANGITIS
- PANCREATITIS
Gallstones: DEFINE and pathophysiology and components of gallstones?
Cholelithiasis is the presence of one or more calculi (gallstones) in the gallbladder.
- Cholesterol.
- Bile pigment.
- Phospholipid.
Gallstones: investigations?
Ultrasound!
ERCP.
Biliary colic: define
The term used for the pain associated with the temporary obstruction of the cystic or common bile duct by a stone migrating from the gall bladder
Gallbladder attack - RUQ pain due to a gall stone blocking the bile duct.
Biliary colic: trigger?
Eating a heavy meal especially one that is high in fat.
(Related with the over-indulgence of fatty food(
Biliary colic vs acute cholecystitis?
Acute cholecystitis has an inflammatory component!
biliary colic has NO INFLAMMATORY RESPONSE -
NO (local peritonitis, fever and raised white blood count)
Biliary colic: symptoms and signs?
- Pain is
1. sudden onset,
2. severe but constant
3. and has a crescendo
characteristic - Most common time for onset of symptoms is mid-evening and usually
lasts till the early hours of the morning - Usually epigastrium pain initially but there may be a right upper
quadrant component- Radiation of pain may occur over the right shoulder and right sub
scapular region
- Radiation of pain may occur over the right shoulder and right sub
- Nausea and vomiting frequently accompany the more severe attacks
Cholecystitis: define?
aetiology?
Inflammation of the gall bladder caused by blockage of the bile duct -> obstruction to bile emptying.
gallstones are responsible for 95% of cases = results in obstruction of gallbladder emptying
Cholecystitis: symptoms?
- continuous epigastric PAIN then PROGRESSES to severe localised RUQ pain. BC of parietal peritoneal involvement
pain associated w tenderness - Fever.
- Raised inflammatory markers.
- NO JAUNDICE!
progressive distension - Obstruction results in an increase of gall bladder glandular secretion leading to progressive distension that, in turn, may compromise the vascular supply to the gall bladder
Cholecystitis: risk factors?
- Obesity.
- Diabetes.
Fat, female, fertile, 40
Cholecystitis: management?
Laparoscopic cholecystectomy.
Ascending cholangitis: define?
Obstruction of biliary tract causing bacterial infection. Regarded as a medical emergency.
Ascending/acute cholangitis is an infection of the biliary tree and most
often occurs secondary to common bile duct obstruction by gallstones
(choledocholithiasis)
Ascending cholangitis: symptoms?
triad?
REYNOLD’S PENTAD
BASO It is a combination of
- Charcot’s triad (right upper quadrant pain, jaundice, and fever) with
- shock (low blood pressure, tachycardia)
- and an altered mental status.
Charcot’s triad:
- Fever.
- RUQ pain.
- JAUNDICE (cholestatic)!Jaundice is cholestatic thus there is dark urine, pale stools and skin may itch
biliary colic
charcot’s triad?
It describes 3 common symptoms of ascending cholangitis:
1. Fever.
- RUQ pain.
- Jaundice (cholestatic)!
Ascending cholangitis: management?
- IV fluid.
- IV antibiotics e.g. cefotaxime and metronidazole. continued after biliary drainage until symptom resolution
- ERCP to remove stone.
- Stenting.
Ascending cholangitis: investigations?
Blood tests:
• Elevated neutrophil count
• Raised ESR and CRP
• Raised serum bilirubin - bile duct obstruction if very high
• Raised serum alkaline phospahtase
• Aminotransferase levels are elevated; ALTs are higher then ASTs
normally
Transabdominal UTRASOUND:
Magnetic resonance cholangiography (MRC):
CT:
Primary Biliary Cholangitis: define?
An autoimmune disease where there is progressive lymphocyte mediated destruction of intra-hepatic bile ducts -> cholestasis -> cirrhosis.
A chronic disorder with progressive destruction of small bile ducts, leading
to cirrhosis
Primary Biliary Cholangitis: epidemiology?
- Females affected more than men. (women aged 40-50 = 90% of pt)!!!!!
- Familial - 10 fold risk increase.
Primary Biliary Cholangitis: pathophysiology?
Lymphocyte mediated attack on bile duct epithelia -> destruction of bile ducts -> cholestasis -> cirrhosis.
Interlobar bile ducts are damaged by CHRONIC AUTOIMMUNE
GRANULOMATOUS INFLAMMATION resulting in cholestasis which may lead
to fibrosis, cirrhosis and portal hypertension
Primary Biliary Cholangitis: symptoms?
why pruritus?
- Itching. Pruritus BC there is a buildup of bilirubin
- Fatigue.
- Dry eyes,
- Joint pains.
- Variceal bleeding.
Asymptomatic patients are discovered on routine examination or screening and may have hepatomegaly, a raised serum alkaline phosphate or anti-
mitochondrial antibodies (AMA)
- Pigmented xanthelasma (yellow fat deposits under skin usually around
eyelids) on eyelids deposits of cholesterol in the creases of the hands may
be seen - steatorrhoea
- malabsorption of fat soluble vitamins
Primary Biliary Cholangitis: management?
Ursodeoxycholic acid; improves liver enzymes; reduces inflammation and portal pressure and therefore the rate of variceal development.
Due to lack of effective medical therapy, primary biliary cirrhosis is a major
indication for LIVER TRANSPLANTATION
Primary Biliary Cholangitis: investigations?
BLOOD TEST 1. Raised IgM. 2. Raised ALP. 3. Positive AMA. (Anti-mitochondrial antibodies (AMAs) - present in 95%, M2 antibody is 98% specific!!!!!!!!!!)
Ultrasound
Liver biopsy
Primary Sclerosing Cholangitis: define?
uncommon chronic liver disease
in which the bile ducts inside and outside the liver progressively decrease in size due to inflammation and scarring (fibrosis).
Primary Sclerosing Cholangitis: pathophysiology?
Inflammation of the bile duct -> strictures and hardening -> progressive obliterating fibrosis of bile duct branches -> cirrhosis -> liver failure.
Primary Sclerosing Cholangitis: symptoms?
- Itching.
- Rigor.
- Pain.
- Jaundice.
75% also have IBD.
Acute Pancreatitis: define:
Syndrome of inflammation of the pancreatic gland initiated by any acute injury
An inflammatory process with release of inflammatory cytokines (TNF alpha, IL-6) and pancreatic enzymes (trypsin, lipase).
Acute Pancreatitis: aetiology?
Name 3 drugs or classes of drugs that can cause acute pancreatitis.
I GET SMASHED:
- I - Idiopathic
- G - Gallstones (majority - 60%)
- E - Ethanol (i.e. alcohol - 30%)
- T - Trauma
- S - Steroids
- M - Mumps
- A - Autoimmune
- S - Scorpion venom
- H - Hyperlipidaemia and (hyper calcaemia)
- E - ERCP (endoscopic retrograde cholangiopancreatography)
- D - Drugs e.g. azathioprine, furosemide (diuretics), corticosteroids,
NSAIDs, ACE inhibitors - Also pregnancy and neoplasia
- NSAIDs.
- Diuretics.
- Steroids.
Acute Pancreatitis: symptoms?
- Severe epigastric pain that radiates to the back. sitting forward may relieve
- Anorexia.
- Nausea, vomiting.
- Signs of septic shock e.g. fever, dehydration, hypotension, tachycardia.!!!
jaundice
- Periumbilical ecchymosis (skin discolouration due to
blood under skin due to bruising) - Cullen’s sign - Left flank bruising (skin discolouration due to blood
under skin due to bruising) - Grey Turner’s sign
How can acute pancreatitis be diagnosed?
2 out of 3 of following
Pancreatitis is diagnosed on the basis of 2 out of 3 of the following:
1. Characteristic severe epigastric pain radiating to the back.
- Raised serum amylase.
- Abdominal CT scan pathology.
Acute Pancreatitis: investigations?
Raised serum amylase
Raised serum lipase
-
Abdominal ultrasound:
- ultrasound of pancreas
The abbreviated glasgow scoring system.
Acute Pancreatitis: management?
- analgesia!!! - eg anti-emetic analgesic IV morphine
BUT!!! Morphine increases sphincter of Oddi pressure and so aggravates pancreatitis. - catheter - to monitor urine output
and ABC approach for shock pt - Drainage of oedematous fluid collections.
- Antibiotics.
- Nutrition. - NIL BY MOUTH - so nasal gastric tube - as less pancreatic enzymes are released so need to support patients nutritionally!)
- Bowel rest.
Acute Pancreatitis: complications?
- Systemic inflammatory response syndrome.
- Multiple organ dysfunction.
- chronic pancreatitis
- pancreatic ascites
- local injury - inflammation can spread locally - acute lung injury AND pancrwatic effusion (a fistula forming between lungs and pancreas
- acute renal failure
- infected pancreatic necrosis)
Chronic Pancreatitis: define
Chronic inflammation of the pancreas leads to irreversible damage.
Chronic Pancreatitis: pathophysiology?
Alcohol -> proteins precipitate in the ductal structure of the pancreas (obstruction of pancreatic ducts) -> thus pancreatic juices start backing up AND inc PA and may distend ducts itself
THEN —> membrane trafficking becomes chaotic - or stimulating inflammation
—>pancreatic fibrosis.
Autoimmune Chronic Pancreatitis: define and investigations?
management?
Chronic pancreatic inflammation which results from an autoimmune process
There are elevated levels of serum gammaglobulins and immunoglobulin G (IgG)
levels - IgG4
It is very steroid responsive. this condition is steroid responsive with glucocorticoid therapy e.g. ORAL
PREDNISOLONE for 4-6 weeks
Chronic Pancreatitis: symptoms?
- Severe abdominal pain.
- Epigastric pain radiating to the back.
- Nausea, vomiting.
- Decreased appetite.
- Exocrine/endocrine dysfunction.
A sign of chronic pancreatitis is exocrine dysfunction. What can be a consequence of this?
A sign of chronic pancreatitis is endocrine dysfunction. What can be a consequence of this?
–
- Malabsorption.
- Weight loss.
- Diarrhoea.
- Steatorrhoea.
Diabetes mellitus.
Chronic Pancreatitis: management?
Opiate e.g. ORAL TRAMADOL - in a controlled environment for severe pain!!!
Alcohol cessation
Diabetes:
• INSULIN
Steatorrhea:
• Pancreatic enzyme supplements
• PPI e.g. LANSOPRAZOLE to help supplement pass stomach
- Duct drainage
- Shock wave lithotripsy to fragment gallstones in the head of pancreas
Portal HTN: define
increased bp in the hepatic portal system >12mmHg
a complication of cirrhosis
Portal HTN: aetiology?
- Cirrhosis and fibrosis (intra-hepatic causes).
- Portal vein thrombosis (pre-hepatic).
- Budd-Chiari (post-hepatic cause).
CIRRHOSIS (80% UK)
- Pre-hepatic:
- Portal vein thrombosis
- Intra-hepatic:
- CIRRHOSIS (80% UK)
- Schistosomiasis (commonest worldwide)
- Sarcoidosis
- Post-hepatic:
- Right heart failure (rare)
- Constrictive pericarditis
- IVC obstruction
portal htn: pathophysiology>
- Portal hypertension can lead to varices. Explain why.
increased bp in the hepatic portal system >12mmHg
can lead to PORTOSYSTEMIC SHUNTS = when blood is diverted away from portal system and backs up into systemic beins
Obstruction to portal blood flow e.g. cirrhosis leads to portal hypertension. Blood is diverted into collaterals e.g. the gastro-oesophageal junction and so causes varices.
Portal HTN: symptoms and signs?
ABCDE ascites bleeding caput medusae (enlarged superficial periumbilical veins) diminished liver function enlarged spleen
Ascites: define
Ascites is the accumulation of free fluid within the peritoneal cavity
that leads to abdominal distension.
Ascites: 4 aetiological reasons?
- low protein = hypoalbuminaemia —> - With less protein e.g. low serum ALBUMIN there is an inability to pull fluid back into the intravascular space
- This fluid then accumulates in the peritoneum - low flow = e.g. cirrhosis, thrombosis, - - Fluid cannot move forwards through system e.g. due to a clot
- Raises pressure in vessels causing fluid to leak out of the vessels
Increased intra-hepatic resistance leads to portal hypertension -> ascites. - Local inflammation e.g. peritonitis. bc it leads to fluid accumulation
- Leaky vessels e.g. imbalance between hydrostatic and oncotic pressures. —> Systemic vasodilation leads to secretion of RAAS, NAd and ADH -> fluid retention.
Ascites: symptoms and signs>Q
- Flank swelling. —> Large distended abdomen -
* *abdominal** swelling may develop over days or weeks - Dull to percuss and shifting dullness.
top 2 but - Respiratory distress and difficulty eating accompany tense ascites
- May be scratch marks on abdomen caused by itching due to jaundice i.e.
liver failure
- Many patients also have peripheral oedema
Ascites: investigations?
- Ultrasound.
2. Ascitic tap.
Ascites: management?
- Restrict sodium.– to help liver and reduce fluid retention (<200mg/day)
- Diuretics.–> Increase renal sodium excretion —Diuretic of choice is an aldosterone antagonist e.g. ORAL SPIRONOLACTONE
since it spares K+ and furosemide - Drainage. —> Drain fluid (paracentesis) - can drain 5 litres at time, used to relieve
symptomatic tense ascites
- Shunts: Transjugular Intrahepatic Portosytemic Shunt (TIPS):
- Used for resistant ascites
- Can be risky
What investigation is it important to do in someone with chronic liver disease and ascites? Explain why it is important.
It is important to do an ascitic tap so you can rule out spontaneous bacterial peritonitis as soon as possible.
Ascites: risk factors?
- High sodium diet
- Hepatocellular carcinoma
- Splanchnic vein thrombosis resulting in portal hypertension
Ascites: pathophysiology?
- Name the 2 main pathophysiological factors that contribute to the formation of ascites.
Poor liver function -> low albumin -> low oncotic pressure -> fluid loss to peritoneal cavity
- High portal venous pressure.2. Low serum albumin.
Hepatic encephalopathy: define and pathopshyiology>?
Hepatic encephalopathy (HE) refers to changes in the brain that occur in patients with advanced, acute (sudden) or chronic (long-term) liver disease. It is one of the major complications of cirrhosis. It can occur suddenly in people with acute liver failure but is more often seen in those with chronic liver disease.
pp
caused by portal htn
decreased blood to liver →
→ less blood detoxification
→ thus build up of toxic metabolites (nitrogenous waste eg ammonia)
→ THUS toxins pass through the BBB = HEPATIC encephalopathy
THIS CAN RESULT IN permanent brain damage as ammonia is neurotoxic to the brain since it halts the Krebs cycle resulting in IRREPARABLE CELL DAMAGE and neural cell DEATH
Also as astrocytes try to clear ammonia (using a process involving the conversion of glutamate to glutamine), the excess glutamine causes an osmotic imbalance and a shift of fluid into these cells hence cerebral oedema - resulting in damage
Peritonitis: define
And aetiology?
The inflammation of the peritoneum
Often due to infection
Aetiology:
1. Bacterial infection due to a perforated organ; spontaneous bacterial peritonitis; infection secondary to peritoneal dialysis.
Eg cirrhosis
- Non-infective causes e.g. bile leak; blood from ruptured ectopic pregnancy.
In general peritonitis tends to be caused mainly by bacteria
Name a bacteria that can cause spontaneous bacterial peritonitis.
- E.coli.
- S.pneumoniae.
the most common organism found on ascitic fluid culture is E. coli
Peritonitis: investigations?
How can spontaneous bacterial peritonitis be diagnosed?
- Blood tests: raised WCC, platelets, CRP, amylase. Reduced blood count.
- CXR: look for air under the diaphragm.
- Abdominal x-ray: look for bowel obstruction.
- CT: can show inflammation, ischaemia or cancer.
- ECG: epigastric pain could be related to the heart.
- B-HCG: a hormone secreted by pregnant ladies.
Blood test—— To monitor/confirm infection - raised white cell count and CRP • Serum amylase to exclude acute pancreatitis
HCG —- to exclude pregnancy
CXR
Abdominal X ray
CT abdomen
——-
By looking for the presence of neutrophils in ascitic fluid.
Peritonitis: symptoms?
- Pain.
- Tenderness.
- Systemic symptoms e.g. nausea, chills, rigor.
- Pain relieved by resting hands on abdomen - thereby stopping movement of peritoneum and thus pain
-
Rigid abdomen
Lying still - people with peritonitis want to stay still
Spontaneous Bacterial Peritonitis: symptoms?
- Dull to percussion.
- Temperature.
- Abdominal pain.
Peritonitis: complications?
- Hypovolaemia.
- Kidney failure.
- Systemic sepsis.
- Paralytic ileus.
- Pulmonary atelectasis (lung collapse).
- Portal pyaemia (pus in the portal vein).
Peritonitis: management?
AND treatment for spontaneous bacterial peritonitis?
- ABC.
- Treat the underlying cause!
- Call a surgeon.
- Set up post-management support.
CEFOTAXIME & METRONIDAZOLE!!!!!!
Oesophageal and portal varices: symptoms of ruptured varices?
- Haematemesis.
- Melaena.
- Abdominal pain.
- Dysphagia.
- Anaemia.
Oesophageal and portal varices: aetiology?
Investigations?
Alcoholism and viral cirrhosis** are some of the leading causes of portal
hypertension
Portal hypertension:
Investigations
Endoscopy to find bleeding source
Oesophageal and portal varices: management ?
Variceal banding - where a band is put around varice using an endoscope, after a few days the banded varix degenerates and falls off leaving a scar - endoscopic therapy - banding
IV TERLIPRESSIN AND IV SOMATOSTATIN!!!!!
Hernia: define?
The abnormal protrusion of an organ into a body cavity it doesn’t normally belong.
Types of hernias / what happens if left untreated?
Reducible hernia:
• Can be pushed back into the abdominal cavity with manual manoeuvring
Irreducible hernia: • Cannot be pushed back into place SO 3: - obstructed - incarcerated - strangulated!!! They can become strangulated and you may not be able to return them into their correct body cavity - irreducible.!@!!!!!!!! BASO IS WHEN Blood supply of the sac is cut off resulting in ischaemia +/- gangrene/perforation of the hernial contents - patent becomes toxic and requires urgent surgery
Hernia: symptoms ?
- Pain
- Palpable lump
(Rarely painful
If painful then indicates STRANGULATION)
Autoimmune hepatitis: management?
- Prednisolone (immunosuppressant)
- Azathioprine to maintain remission
If prednisolone not responded to/ intolerated = ciclosporin (another immunosuppressant)
Autoimmune hepatitis: Key presentations and investigations ?
Presents as hIGH ALT Itchiness Jaundice (yellow skin and eyes) Malaise Anorexia Nausea
raised serum bilirubin,
raised AST,
raised ALT,
raised ALP,
raised IgG,
and a positive ASMA.
Wernicke’s encephalopathy: define and symptoms?
prevention/reversal?
occurs from alcohol withdrawal, occurs 6-24 hours after last drink and lasts up to a week
ataxia, confusion and nystagmus
Opthalmoplegia
IV thiamine
Haemochromatosis: define
baso iron overload
Inherited disorder of iron metabolism in which there is increased intestinal
iron absorption leads to iron deposition in joints, liver, heart, pancreas,
pituitary, adrenals and skin
→ leads to eventual fibrosis and functional organ failure
Haemochromatosis: AETIOLOGY?
HFE gene mutation on chromosome 6, this is an AUTOSOMAL
RECESSIVE gene (i.e. sufferer must be homozygous) - MOST COMMON
CAUSE
- There are other gene mutations responsible and one is AUTOSOMAL
DOMINANT - but not as common, but means sufferer can be
heterozygous - High intake of iron and chelating agents (e.g. ascorbic acid)
- Alcoholics may have iron overload
Haemochromatosis: PP?
What protein is responsible for controlling iron absorption?
HFE gene protein interacts with the transferrin receptor 1, which is a mediator in intestinal iron absorption
—-> Hepatic expression of the hepcidin gene is decreased hepcidin controls iron absorption
Excess iron is then gradually taken up by the liver and other tissue over a long
period
- The iron itself precipitates fibrosis
Uncontrolled intestinal iron absorption leads to deposition in the liver, heart and pancreas -> fibrosis -> organ failure.
Hepcidin.
Levels of this protein are decreased in haemochromatosis.
Haemochromatosis: investigations?
What histological stain can be used for haemochromatosis?
- Raised ferritin. - raised serum iron
- HFE genotyping.
- Liver biopsy.
• Can establish extent of tissue damage and disease severity
MRI:
• Detects iron overload
Perl’s stain.
haemochromatosis: symptoms?
- Hepatomegaly.
- Cardiomegaly.
- Diabetes mellitus.
- Hyperpigmentation of skin.
- Lethargy.
