1
Q
how is bilirubin produced?
A
- by product of haeme metabolism.
- generated by senescent RBC’s in spleen.
2
Q
what is unconjugated bilirubin initially bound to?
A
albumin
3
Q
why does the liver conjugate bilirubin?
A
helps to solubilise it
4
Q
what is a pre-hepatic, hepatic and post-hepatic cause of elevated bilirubin levels?
A
pre: haemolysis
hepatic: parenchymal damage
post: obstructive
5
Q
what can a high AST/ALT ratio point towards?
A
alcoholic liver disease
6
Q
what could elevated levels of alkaline phosphatase (ALP) indicate?
A
elevated with obstruction or liver infiltration
7
Q
What could elevated levels of Gamma GT indicate?
A
alcohol use
NSAID use
8
Q
what is an albumin level test important for? and what could low levels suggest?
A
- important for synthetic function of liver.
- chronic liver disease.
- kidney disorders and malnutrition.
9
Q
describe the importance of prothrombin time test?
what does it test?
A
- extremely important test for liver function.
- tells degree of liver dysfunction.
- used to calculate scores to decide stage of liver disease, who needs a liver transplant and who gets a liver transplant.
- tests how long for a clot to form in a blood sample.
10
Q
what do creatinine tests help to determine?
A
- essentially kidney function.
- determines survival from liver disease.
- critical assessment for need for transplant.
11
Q
why do we do a platelet count test?
A
- liver is an important source of thrombopoietin.
- cirrhosis results in splenomegaly.
- platelets low in cirrhotic subjects as a result of hypersplenism.
- indirect marker of portal hypertension.
12
Q
when is jaundice detectable?
A
when total plasma bilirubin levels exceed 34 micromol/L
13
Q
what are history clues for pre-hepatic jaundice?
A
- history of anaemia (fatigue, dyspnoea, chest pain).
- acholuric jaundice. (no yellowing of urine)
14
Q
what are history and visual clues for hepatic jaundice?
A
- risk factors for liver disease (IVDU, drug intake).
- decompensation (ascites, variceal bleed, encephalopathy).
15
Q
what are history clues for post-hepatic jaundice?
A
- abdominal pain.
- cholestasis (pruritus (itchiness), pale stools, high coloured urine).
16
Q
what are clinical examination clues for pre-hepatic jaundice?
A
- pallor.
- splenomegaly.
17
Q
what are examination clues for hepatic-jaundice that can be seen from inspection?
A
- stigmata of CLD (spider naevi, gynaecomastia).
- ascites.
- flapping tremor.
18
Q
what is an examination clues for post-hepatic jaundice?
A
palpable gall bladder (Courvoisier’s sign).
19
Q
Del
A
Del
20
Q
what is the most important imaging test used in investigation of jaundice?
A
Ultrasound
21
Q
what does ERCP do?
A
radiological imagine of biliary tree performed endoscopically to get to ampulla of vater and x -rays to see biliary tree.
22
Q
when is ERCP used?
A
can spot obstructions:
- dilated biliary tree (+/- stones or tumour).
- acute gallstone pancreatitis.
- post op biliary complications.
can be used surgically:
- can also perform stenting of biliary tract obstruction whilst using ERCP.
- stone retrival > basket
- sphincterotomy
23
Q
when is endoscopic ultrasound used for the biliary tree?
A
- characterising pancreatic masses.
- staging of tumours.
- fine needle aspirate (FNA) of tumours and cysts.
- excluding biliary microcalculi
24
Q
what is the importance of a liver biopsy?
A
- important for definitive diagnosis or certain conditions e.g. autoimmune hepatitis.
- important to confirm diagnosis e.g. primary biliary cholangitis, drug-induced liver injury.
- important for staging of severity e.g. alcoholic hepatitis, non-alcoholic fatty liver disease.
25
when is liver disease considered chronic?
if it persists beyond 6 months.
26
what is the clinical presentation of compensated chronic liver disease?
asymptomatic stage. Compensated patients do not have ascites, variceal hemorrhage, hepatic encephalopathy, or jaundice.
- routinely detected on screening tests.
- abnormality of liver function tests.
27
what is the clinical presentation of decompensated chronic liver disease?
- ascites
- hepatorenal syndrome
- variceal bleeding
- hepatic encephalopathy
- hepatocellular carcinoma potentially.
28
what is ascites?
the abnormal accumulation of fluid within the peritoneal cavity.
- typically associated with liver disease > cirrhosis.
29
investigations for ascites
- ascitic tap (paracentesis) > content of ascitic fluid.
initial evaluation:
- protein & albumin concentration.
- cell count and differential.
- SAAG.
30
describe the serum ascites albumin gradient (SAAG) calculation
- can help to determine cause of ascites.
- IT IS CALCULATED BY SUBTRACTING THE ALBUMIN CONCENTRATION OF THE ASCITIC FLUID FROM THE SERUM ALBUMIN CONCENTRATION.
31
what does a high SAAG (>1.1g/dl) suggest?
- portal hypertension.
- CHF (congestive heart failure)
- constrictive pericarditis.
- Budd Chiarri.
- Myxedema.
- Massive liver metastases.
32
what does a low SAAG (<1.1 g/dl) suggest?
- indicates non-portal hypertension and suggests a peritoneal cause of ascites.
33
treatment for ascites?
diuretics
large volume paracentesis
TIPS
aquaretics
liver transplantation
34
describe hepatorenal syndrome
Hepatorenal syndrome (HRS) is a multiorgan condition of acute kidney injury seen in those with advanced liver disease. Patients with this condition present with signs and symptoms of liver failure as well as decreased urination as they become oliguric
35
what is hepatic encephalopathy?
confusion due to liver disease
36
what is the most common cause of liver cancer?
hepatocellular carcinoma
37
presentation of hepatocellular carcinoma?
- decompensation of liver disease.
- abdominal mass.
- abdominal pain.
- weight loss.
- bleeding from tumour
38
what is uses in the diagnosis of hepatocellular carcinoma?
tumour markers: AFP. (alpha fetoprotein)
radiological tests:
- US.
- CT scan.
- MRI.
- liver biopsy perfomed very rarely.
39
list the treatment options for hepatocellular carcinoma
- Hepatic resection
- Liver transplantation
- Chemotherapy
- Locally ablative treatments
>Alcohol injection
>Radiofrequency ablation
- Sorafenib (Tyrosinase kinase inhibitor)
- Hormonal therapy: Tamoxifen
40
which types of hepatitis are enteric viruses?
A and E
41
which types of hepatitis are parenteral viruses?
B, C and D
42
which types of hepatitis cause self limiting, acute infections?
A & E
43
which types of hepatitis cause chronic disease?
B, C & D
44
how many people die each yer from causes of viral hepatitis?
approx 1 million
45
what groups of pple should be immunised for hepatitis A virus?
- travellers
- patient with chronic liver disease
- IVDU (especially with HCV or HBV)
- haemophiliacs
- occupational exposure (lab workers)
- men who have sex with men.
46
what does the presence of IgM anti-HBc antibodies indicate?
acute hepatitis B infection
47
what does the presence of IgG anti-HBc antibodies indicate?
chronic infection/exposure
48
what does the presence of anti-HBe antibodies indicate?
inactive virus
49
what does the presence of HBsAg in the blood indicate?
presence of hepatitis B virus
50
what is the natural history of chronic hepatitis B?
- no further progression, not all patients have progressive disease.
OR
- cirrhosis which can cause hepatocellular carcinoma and end-stage liver disease.
51
what are the treatment options for hepatitis B virus?
- pegylated interferon alfa-2a is the first line therapy.
- oral antiviral drugs such as entecavir and tenofovir.
52
what is the most common cause of acute hepatitis in Grampian?
hepatitis E
53
Non-alcoholic fatty liver disease is an umbrella term encompassing which three entities?
- simple steatosis (fat build up in liver cells)
- non-alcoholic steatohepatitis (NASH).
- fibrosis and cirrhosis.
54
what are risk factors for NAFLD?
modifiable and non-modifiable
- diabetes mellitus.
- obesity.
- hypertiglyceridemia.
- hypertension.
- age
- ethnicity (e.g. hispanics)
- genetic factors e.g., PNPLA3 gene
55
what is the treatment for NAFLD?
- lifestyle changes (diet, exercise).
- insulin sensitizers e.g. metformin.
- glucagon-like peptide 1 (GLP-1) analogues e.g. liraglutide.
- obeticholic acid
- vitamin E
- weight reduction surgery
56
what are three autoimmune liver diseases?
autoimmune hepatitis
primary biliary cholangitis
primary sclerosing cholangitis
57
what is a long-term drug is used in the treatment of autoimmune hepatitis?
azathioprine
58
what antibody is elevated in autoimmune hepatitis?
IgG
59
What antibodies are elevated in primary biliary cholangitis?
IgM
anti-mitochondrial antibodies
60
pharmacological treatment of primary biliary cholangitis?
ursodeoxycholic acid (UDCA) to slow disease progression
61
primary sclerosing cholangitis is positive for what antibodies?
anti-smooth muscle and antinuclear antibodies and myeloperoxidase antineutrophil cytoplasmic antibody (ANCA)
62
treatment for primary sclerosing cholangitis
- biliary stents via ERCP.
- liver transplant
63
what changes occur to the liver with alcoholism?
- steatosis (fatty liver)
- steatohepatitis (fatty liver with inflammation)
- neutrophil infiltration
- fibrosis, cirrhosis
64
what are signs of chronic liver disease?
-spider naevi
-palmar erythema
- gynaecomastia
- loss of axillary and pubic hair
- ascites
- encephalopathy
- jaundice
- muscle wasting
65
what imaging would be performed when investigating alcoholic liver disease?
US
66
how is hepatic encephalopathy graded?
1-4
1- mild confusion
4- coma
67
what can cause hepatic encephalopathy as a result of liver failure?
infection
drugs
constipation
GI bleed
electrolyte disturbance
68
what is the treatment for hepatic encephalopathy?
- bowel clear out, lactulose, enemas.
- antibiotics
- supportive: ITU, airway support, nasogastric tube for meds
69
what conditions can alcoholism cause that are liver related?
encephalopathy
spontaneous bacterial peritonitis
alcoholic hepatitis
fatty liver disease
70
what are signs and symptoms of spontaneous bacterial peritonitis?
- abdominal pain
- fever, rigors
- renal impairment
- signs of sepsis: tachycardia, temperature
71
investigation for spontaneous bacterial peritonitis?
ascitic tap (paracentesis)
- fluid protein and glucose levels
- cultures
- white cell count
72
whats the treatment for spontaneous bacterial peritonitis?
IV antibiotics
ascitic fluid drainage
IV albumin infusion (20% ALBA)
73
what is the presentation of alcoholic hepatitis?
- jaundice
- encephalopathy
- infection common
- decompensated hepatic function
-> low albumin and raised prothrombin time/INR
74
what is used for the diagnosis of alcoholic hepatitis?
- raised bilirubin
- raised GGT and AlkP
- alcohol history
- exclude other causes
75
when are steroids indicated in the treatment of alcoholic hepatitis?
only if grading severe
Glasgow alcoholic hepatitis score >9
76
treatment of alcoholic hepatits may include
supportive treatment
steroids
nutrition
77
what is the length range of the colon?
1.5-1.8 metres?
78
what muscle layer of the large intestine is incomplete?
longitudinal muscle layer
79
what mucus secreting cells are present in large numbers in the large intestine? and why is this?
goblet cells
secrete mucus > lubrication for movement of faeces
80
the external anal sphincter is composed of which muscle type?
skeletal muscle
81
how does the colon produce solid faecal pellets?
actively transports sodium from lumen into blood > osmotic absorption of water > dehydration of chyme > solid faecal pellets
82
what important process occurs in the colon?
bacterial fermentation of undigested carbohydrates
83
what are the products of bacterial fermentation of undigested carbs?
- short chain fatty acids
- vitamin K (important for blood clotting).
- gas - nitrogen, CO2, hydrogen, methane, hydrogen sulphide.
84
what maintains faecal continence?
anus closed by internal anal sphincter (smooth muscle under automatic control) and external anal sphincter (skeletal muscle under voluntary control).
85
describe the process of defaecation
following a meal:
- wave of intense contraction (mass movement contraction) from colon > rectum.
- distension of rectal wall produced by mass movement of faecal material into rectum > mechanoreceptors > defaecation reflex > urge to defaecate.
86
explain the defaecation reflex
Under parasympathetic control - via splanchnic nerves:
- contraction of rectum
- relaxation of internal and contraction of external anal sphincters.
- increased peristaltic activity in colon.
- increased pressure on external anal sphincter > relaxes under voluntary control > expulsion of faeces.
87
what symptoms are associated with constipation?
headaches
nausea
loss of appetite
abdominal distension
88
what is diarrhoea?
too frequent passage of faeces which are too liquid
89
what are some causes of diarrhoea?
pathogenic bacteria
protozoans
viruses
toxins
food
90
what are examples of enterotoxigenis bacteria?
Vibrio cholerae
E. coli
91
how do enterotoxigenic bacteria cause diarrhoea?
- produce protein enterotoxins which maximally turn on intestinal chloride secretion from crypt cells > increased H2O secretion.
- elevate intracellular second messengers: cAMP, cGMP, calcium.
- H2O secretion swamps absorptive capacity of villus cells > profuse watery diarrhoea.
92
do enterotoxins damage villus cells?
no
93
what is the treatment for secretory diarrhoea?
- give sodium/glucose solution > drive H2O absorption > rehydration.
- wash away infection.
- oral rehydration therapy (ORS).
94
where does gastric acid neutralisation, digestion and iron absorption take place?
duodenum
95
where does 95% of nutrient absorption take place?
jejunum
96
how is the absorptive surface area of the small intestine enhanced?
circular folds (plicae)
villi
microvilli
97
what is the function of a crypt cell in the small intestine?
secretes Cl and water
98
how much water does the small intestine secrete daily?
1500ml H2O per day
99
what causes the small intestine to secrete water?
water is secreted passively (osmotically) as a consequence of active secretion of chloride into intestinal lumen.
100
why is H2O secretion important for a normal digestive process?
- maintains lumenal contents in liquid state.
- promotes mixing of nutrients with digestive enzymes.
- aids nutrient presentation to absorbing surface.
- dilutes and washes away potentially injurious substances.
101
what is the function of segmentation contractions?
provides thorough mixing of contents with digestive enzymes and brings chyme into contact with absorbing surface.
102
does the frequency of segmentation contraction decrease or increase moving down intestine > rectum?
decrease
103
what initiates segmentation contractions? like what cells in what tissue?
depolarisation generated by pacemaker cells in longitudinal muscle layer
104
following the absorption of nutrients, what movement stops and what starts?
segmentation stops, peristalsis starts
105
what is the migrating motility complex (MMC)?
pattern of peristaltic activity travelling down small intestines (starts in gastric antrum).
- as one MMC ends (terminal ileum) another begins.
106
what causes cessation of MMC and initiation of segmentation contractions~?
arrival of food in stomach.
107
what is the function of MMC?
move undigested material into large intestine
limit bacterial colonisation of small intestine
108
what hormone is involved in initiation of MMC?
motilin
109
what neurones mediate peristalsis?
myenteric plexus
110
explain the gastroileal reflex
gastric emptying > segmentation activity in ileum:
- opening of ileocaecal valve (sphincter).
- entry of chyme into large intestine.
- distension of colon.
- reflex contraction of ileocaecal sphincter (prevents backflow into small intestine).
111
what surgery is used to remove gall stones?
cholecystectomies
112
what is the composition of gallstones?
main types are gallstones:
- pigment (<10%).
- cholesterol (90%).
- mixed.
113
what are risk factors for developing gallstones?
fair, fat, female, forty
- obesity.
- female sex.
- diabetes.
- family history.
- chronic loss of bile salts.
- oral contraceptive pill.
- pregnancy.
- rapid weight change.
- chronic haemolysis.
- increasing age.
114
what is the clinical presentation of gallstones?
- can be asymptomatic.
- dyspeptic symptoms.
- biliary colic.
- acute cholecystitis.
- empyema.
- perforation.
- jaundice.
- gallstone ileus.
115
what is choledocho-lithiasis?
the presence of at least one gall stone in the common bile duct.
116
what are investigation of gallstones?
- basic blood panel: raised LFTs and C-reactive protein.
- EUS > first-line
- CT scan
- MRCP
- ERCP > used for therapeutic intervention.
117
management of gallstones?
biliary drainage: via ERCP, PTC, or surgical means.
- cholecystectomy.
118
what is cholangiocarcinoma?
cancer of the bile ducts
can be intrahepatic, hilar or extrahepatic
119
what is the only curative option for intrahepatic cholangiocarcinoma?
surgery
120
presentation of cholangiocarcinoma?
jaundice
weight loss
abdominal pain
itchiness
121
what are surgical options for ampullary tumours?
endoscopic excision
trans-duodenal excision
pancreatico-duodenectomy
122
What symptoms are suggestive of chronic pancreatitis?
- chronic or recurrent upper abdominal pain
- acute pancreatitis
- recurrent acute pancreatitis
- diabetes
- exocrine insufficiency
123
what are investigations in chronic pancreatitis?
- contrast enhanced CT
- MRI with MRCP
- EUS
124
what is the non-surgical management of chronic pancreatitis?
- well-balanced diet
- non-opioid analgesics
- trial of antioxidants and pancreatic enzymes
- cessation of alcohol and tobacco use
125
describe the process of endoscopic therapy in the treatment of pancreatic ductal obstructions in patients with CP
- widening of papillary orifice
- balloon dilation for pancreatic duct stricture/basket removal of pancreatic ductal stones.
- stent placement within pancreatic duct.
126
describe the surgical management of pancreatic duct obstructions in patients with CP
local head excavation with lateral pancreaticjejunostomy:
- pancreatic head excavation and pancreatotomy for surgical emoval of pancreatic ductal stones.
- side to side anastomosis of pancreas and jejunum.
- pancreatic secretions flow directly into jejunum.
127
what imaging is used to investigate pancreatic cysts?
CT
MRI
MRCP
128
what imaging is superior in diagnosing pancreatic cysts?
contrast-enhanced EUS
129
del
del
130
what is the aetiology of chronic pancreatitis?
- chronic alcohol excess (80%) of cases.
- genetic factors: cystic fibrosis.
- obstructive causes: pancreatic cancer.
- metabolic causes: elevated triglycerides.
131
what are signs and symptoms of chronic pancreatitis?
- epigastric pain which is typically exacerbated after eating fatty food and relieved by sitting forward.
- symptoms of exocrine dysfunction, such as malabsorption and steatorrhoea.
- symptoms of endocrine dysfunction, such as diabetes mellitus > thirst and polyuria.
- epigastric tenderness and signs of chronic liver disease > alcohol as a cause.
132
what are the complications of chronic pancreatitis?
Complications of chronic pancreatitis can be local (such as pseudocyst or pancreatic cancer) or systemic (endocrine dysfunction leading to diabetes mellitus, or exocrine dysfunction leading to malabsorption and steatorrhoea).
133
what are the non-specific symptoms that early stage pancreatic cancer often presents with?
malaise
abdominal pain
nausea
weight loss
134
what are the signs and symptoms of advanced pancreatic cancer?
- obstructive jaundice (painful).
- diabetes mellitus.
- pancreatitis, exocrine dysfunction with steatorrhoea (fatty faeces).
- paraneoplastic syndromes.
- disseminated intravascular coagulation.
- ascites.
- portal hypertension.
135
what is the common surgical procedure for tumours in the head of the pancreas called? (curative resection)
Kausch-Whipple procedure (radical pancreaticoduodenectomy)
136
what are the palliative options in pancreatic cancer?
- endoscopic stent insertion into the common bile duct.
- palliative surgery if endoscopic stent insertion fails.
- chemotherapy.
- radiotherapy.
137
del
del
138
what is the aetiology of acute pancreatitis? USE GET SMASHED mnemonic
- gallstones (most common ww)
- ethanol (most common europe)
- trauma
- steroids
- Mumps
- autoimmune disease (SLE)
- scorpion bite
- hypercalcaemia, hypertriglycerideaemia, hypothermia.
- ERCP
- drugs
139
signs and symptoms of acute pancreatitis?
abdominal pain
nausea
vomiting
collapse
pyrexia
dehydration
abdominal tenderness
circulatory failure
140
what are the diagnostic investigations in acute pancreatitis?
- FBC, urea and electrolytes.
- LFTs
- lipase and amylase.
141
what imaging investigations can be used to help identify causes of acute pancreatitis?
- US abdomen > gallstones.
- MRCP > obstructive pancreatitis.
- ERCP > can also be therapeutic.
- CT > identify complications at later stage.
142
del
del
143
what are the signs and symptoms of alcohol withdrawal syndrome?
Sweating
Tachycardia
Hypertension
Anxiety
Headache
Insomnia
Visual hallucinations
Weakness
Nausea
Retching
Vomiting
Seizures
144
what are the three main reasons Ascites develops?
- portal hypertension
- low serum albumin causing reduced plasma oncotic pressure.
- hypoperfusion of the kidneys leading to activation of the renin-angiotensin system leading to salt and water retention.
145
what is one of the main complications of ascites?
spontaneous bacterial peritonitis
146
how is spontaneous bacterial peritonitis diagnosed?
ascitic tap > culture > raised neutrophil level
147
how would you expect transferrin and ferritin levels to be effected by iron deficiency? explain your answer
- high transferrin, low ferritin.
- in iron deficiency the liver increases production of transferrin to increase iron uptake and maintain iron homeostasis.
- ferritin acts as an iron store so decreases when there is low iron levels in the blood.
148
for which conditions might CREON and pancreatin prescribed?
cystic fibrosis
pancreatic cancer
chronic pancreatitis
149
what is used to diagnose Crohn's disease?
endoscopy
