Liver & Friends Flashcards
1
Q
What pathways can alcohol take once in the hepatocytes?
A
1.Involves enzyme alcohol dehydrogenase (ADH). Happens in the cytosol
2.Involves catalase in peroxisomes
3.Alcohol is converted by enzyme Cytochrome P450 2E1
=all pathways lead to the conversion of alcohol to acetaldehyde
2
Q
Why is there an increase of NADH in the hepatocytes if someone drinks excessive amount of alcohol and what is the consequence of this
A
Once ADH enzyme is used to convert alcohol, it needs NAD+. This is then converted to NADH
As NADH levels increase, NAD+ levels decrease.
Effects:
1.Higher NADH levels tell cell to start producing more fatty acids
2.Lower NAD+ levels result in less fatty acid oxidation
=More fat production in the liver
3
Q
What is excessive fat in the liver also known as
A
Fatty change/fatty liver
The liver becomes large, heavy, greasy, tender. Also yellowish in appearence due to fat deposits (Steatosis)
Other symptoms are not present
4
Q
When alcohol dehydrogenase is converted to acetaldehyde what does it produce.
A
Reactive oxygen species e.g:
Hydrogen peroxide
Hydroxyl radical
Superoxide anion
Can react with DNA + proteins damaging cells
5
Q
How are acetaldehyde adducts created?
A
Acetaldehyde binds to macromolecules, enzymes, cell membrane forming acetaldehyde adducts, inhibitng the cell.
6
Q
What happens when acetaldehyde adducts are formed
A
Immune system recognises acetaldehyde adducts as foreign.
This means that hepatocytes get destroyed via neutrophil infiltration
Cells become inflamed and damged, patients have developed alcoholic hepatits
7
Q
Histological appearence in a patient developing alcoholic hepatitis
A
Formation of mallory bodies: damaged intermediate filaments located in the cytoplasm
8
Q
What can you find in someone with alcoholic liver disease
A
Perivenular fibrosis: Scar tissue around central veins
Hepatomegaly: Causing pain and enzymes to leak out (ALT,AST). More AST in hepatatis. Elevated ALP + GGT.
Neutrophilic leukocytosis
Thrombocyopenia
Hypoglycaemia
9
Q
Treatment for alcoholic liver disease
A
Stop alcohol consumption
Corticosteroids: suppress immune system
10
Q
Complications of alcohol-induced liver disease
A
Cirrhosis
Liver Failure
11
Q
Diagnosis for alcohol-induced liver disease
A
Ultrasound
CT scan
MRI
Liver Function test
12
Q
What is non-alcoholic fatty liver disease
A
Spectrum of diseases
13
Q
What causes non-alcoholic fatty liver disease
A
Results from fat deposition in the
14
Q
Who is affected by non-alcoholic fatty liver disease
A
Affects individuals with metabolic syndrome with 3 of 5 folowing diagnoses:
Obesity
Hypertension
Diabetes
Hypertriglyceridemia
Hyperlipidemia
15
Q
What plays an important role in the development of non-alcoholic fatty liver disease
A
Insulin Resistance
16
Q
Appearence of a fatty liver
A
Widespread steatosis
-Liver appears large
-Soft
-Yellow
-Greasy
17
Q
Pathology of non-alcoholic fatty liver disease
A
18
Q
Histological appearence of pateint with non-alcoholic fatty liver disease
A
Bloating/Dying hepatocytes
Mallory-Denk Bodies: tangles of intermediate filaments
19
Q
How does fibrosis in the liver occur
A
Chronic steatohepatitis can cause stellate cells to lay down fibrotic tissue
20
Q
What does fibrosis lead to?
A
Cirrhosis
21
Q
Symptoms of non-alcoholic liver disease
A
+Because hepatocytes are being destroyed there can be an increase in liver enzymes:
Aspartate transaminase (AST)
Alanine transaminase (ALT)
Can also get increased ALT & sometimes AST
22
Q
Diff of liver enzyme levels in non-alcoholic fatty liver disease vs. alcoholic fatty liver disease
A
23
Q
Diagnosis of non-alcoholic fatty liver disease
A
24
Q
Treatment for non-alcoholic fatty liver disease
A
25
Progression of non-alcoholic fatty liver disease
26
What is hepatitis
Inflammation of the liver
27
Lifecycle of Hepatitis A virus
Hepatitis A virus binds to receptors on hepatocytes and Kupffer cells entering via endocytosis.
The virus reproduces and exits via exocytosis
After exiting the cell the viral particles are secreted into bile and excreted via GI tract
Cells are recruited to liver. (See pic)
Immune cells are secreted against virus. B cells create IgM & IgG antibodies
28
What is the result of Hepatits A viral infection?
Liver Damage
29
On a biopsy what would liver damage look like
Ballooning hepatocytes
Councilman Bodies
Monocyte infiltration
30
Life cycle of hepatitis E
Life cycle unknown
Thought to be similar to Hepatitis A
31
What patients with Hepatitis E develop chronic disease
Immunocomprimised patients esp.Organ Transplant
32
Complications of hepatitis E
33
How long does infection of hepatitis A & E last
Last 2-4 weeks
Most infected individual recover
34
Diagnosis of Hepatitis A & E infection
35
Treatment for Hepatitis A & E
36
Prevention of Hepatitis A & E infection
37
What virus is Hep B virus
Hepadnavirus (DNA virus)
38
What virus is Hep D virus
Deltavirus (RNA virus)
*Needs Hep B to replicate*
39
What are sources of Hep B virus
*Blood*
Milk
Amniotic fluid
Vaginal secretions
Semen
40
Routes of transmission for the Hep B virus
Birth, placenta barrier
41
How is a Hep D virus disease only caused?
Active Hep B infection
42
Hep B virus summary
43
Hep D virus summary
44
Hep C virus summary
45
Hep A & E virus summary
46
What is autoimmune hepatitis
Resulting inflammation of liver tissue, because they're being attacked by your own immune cells
47
Causes of autoimmune hepatitis
Unknown
Environmental triggers
Genetic predisposition: young women. F:M = 4:1
48
Other associations of Autoimmune hepatitis
Hashimoto's thyroiditis
Graves' Disease
49
Symptoms of Autoimmune hepatitis
50
Types of autoimmune hepatitis and diagnosis for them
51
Treatment for autoimmune hepatitis
52
What is liver cirrhosis
When the liver becomes seriously scarred + damaged to the point where it's no longer reversible, at which point it becomes fibrotic. This is known as cirrhoisis
53
What is liver cirrhosis referred to as
"End-stage" liver damage
54
What are classic signs of cirrhosis
regenerative nodules
fibrosis
55
What cells mediate fibrosis
stellate cells
56
Complications of liver cirrhosis 1
Portal hypertension
Ascites
Congestive Splenomegaly
Hepatorenal failure
Coma
Asterixis
57
Complications of liver cirrhosis (2)
58
Symptoms of liver cirrhosis
*Jaundice*
59
Diagnosis of liver cirrhosis
60
Treatment of liver cirrhosis
Liver transplant
Treat underlying cause
61
What is acute liver failure/fulminant hepatic failure
When the liver loses function rapidly in some days/weeks
62
Complications of liver failure
Oedema
Jaundice
Coagulopathy
Encephalopathy
63
What causes acute liver failure
Due to extensive damge to liver cells
Can include:
1.Taking too much paracetemol
2.Usage of prescription medication: antibiotics, NSAIDs
3.Infected by hepatitis A,B,E
4.Epstein-Barr, Herpes simplex viruses, cytomegalovirus
5.Autoimmune disease
6.Fatty liver
7.Wlson's disease
8.Budd Chiari-syndrome
64
Symptoms of acute liver failure
1.Nausea & vomiting
2.Jaundice
3.Sleepiness
4.Pain in upper right abdomen
5.Tremors
6.Confusion
7.Abdominal swelling
8.Yellowing of the eyes
9.Skin become tender
65
Diagnosis of liver failure
CT scan
Ultrasound
MRI
66
Treatment for acute liver failure
Liver transplant
Medications to reverse poisoning
67
Causes of chronic liver failure
Alcoholic liver Disease
Viral Hepatitis
NASH
68
What is jaundice?
Yellowing of the skin and conjuctiva. Jaundice is caused by elevated serum bilirubin levels.
Jaundice is only detected when serum bilirubin levels are greater than 2mg/dL
69
What is the earliest sign of jaundice and increased bilirubin in blood
1.Looking at sclera of eyes
2.Looking at skin
70
What are two types of disorders that have increased unconjugated bilirubin and similar presentation of jaundice
Extravascular haemolytic anaemia
Ineffective haematopoesis
71
Breakdown of Hb
1.Blood cells near end of lifespan (120 days) are phagocytosed by macrophages in the reticuloendothelial system
2. Haemglobin if broken down into heme and globin. Globin is further broken down into amino acids. Heme is broken down into iron and protoporphyrin.
3. Protoporphyrin is converted into UCB
4.Albumin binds to UCB (lipid soluble) and taken up by hepatocytes
5.UCB is conjugated by enzyme uridine glucuronyl transferase (UGT) into conjugated bilirubin.
6.Conjugated bilirubin is secreted out the bile canaliculi where it drains into the bile ducts and sent to gallbladder for storage as bile
7.When food is ingested, the gallbladder secretes bile and CB, it moves through the common bile duct to the duodenum of the small intestine and is converted to urobiliongen (UBG) by intestinal microbes in the gut. Urobilinogen is reduced to stercobilin which is excreted. Urobilinogen is recycled into blood and spontaneously oxidise into urobilin and excreted or goes back to liver
72
Disorders with increased UCB
1.Physiologic jaundice of the newborn. Treatment: phototherapy
2.Dyserythropoesis
3.Extravascular haemolysis
4.intravascular haemolysis
5.Extravasation
6.Medications
Genetic defects:
2.Gilbert's syndrome
3.Crigler Najjar syndrome
73
Disorders associated with increased CB
Intrahapatic causes:
Viral hepatitis
Alcoholic hepatitis
Non-alcoholic sigatohepatitis
drugs & toxins
sepsis
TPN
Post operative patients
Post hepatic causes:
Gall bladder carcinoma
Cholelithcasis
Parasites
Lymphoma
Pancreatic tumour
ERCP
74
Jaundice with increased CB & UCB
Viral hepatitis
75
Investigations for jaundice
Initial Investigations:
Liver Function Test: Bilirubin, Albumin
INR
Jaundice with UCB:
LFT is not deranged. Consider haemolytic screen:
FBC
Blood Film
Reticulocytes
Haptoglobin
LDH
Coombs test
Jaundice with CB intrahepatic:
AST & ALT elevated
If liver injury hepatitis screen
Jaundice with CB obstructive:
ALP is elevated
Need imaging
76
In obstructive jaundice where would gallstones be located?
In the common bile duct.
77
What is pre-hepatic jaundice?
When a condition or infection speeds up the breakdown of red blood cells. This causes bilirubin levels in the blood to increase, triggering jaundice.
78
What conditions can cause pre-hepatic jaundice?
Malaria, sickle-cell anaemia, thalassaemia.
79
What is intra-hepatic jaundice?
When there is a problem in the liver – for example, damage due to infection or alcohol, this disrupts the liver’s ability to process bilirubin.
80
What can cause intra-hepatic jaundice?
HepatitisA/B/C, alcoholic liver disease, Gilbert’s syndrome, drug misuse.
81
What is Gilbert’s syndrome?
A genetic syndrome where the liver has problems breaking down bilirubin at a normal rate. The conjugated bilirubin is normal but the unconjugated bilirubin levels will be elevated.
82
What is post-hepatic jaundice?
When the bile duct system is damaged, inflamed or obstructed, which results in the gallbladder being unable to move bile into the digestive system.
83
What can cause post-hepatic jaundice?
Gall stones, pancreatic cancer, gallbladder cancer, pancreatitis
84
What is Wernicke's encephalopathy
Acute and reversible encephalopathy due to deficiency of thiamine (Vitamin B1)
85
Risk Factors of Wernicke's encephalopathy
Patients with poor nutritional absorption, intake or loss
1. Chronic alcoholism
2. Anorexia nervosa
3. Hyperemesis
4. Prolonged fasting/starvation
5. GI surgery
6. Systemic malignancy
7. Transplantation
8. AIDS
86
Symptoms of Wernicke's Encephalopathy (WE)
Triad of Symtpoms (CAN)
**C**onfusion (Encephalopathy): Profound disorientation, indifference, inattentiveness
**A**taxia: Stance and gait, polyneuropathy, cerebellar involvement
Oculomotor dysfunction **N**ystagmus:
Other:
Coma
Hypotension
Hypothermia
87
Treatment for Wernicke's Encephalopathy
IV thiamine
DO NOT administer glucose BEFORE thiamine can worsen WE
88
Complication of Wernicke's encephalopathy
Korsakoff's syndrome: chronic condition that is a consequence of Wernicke's encephalopathy
89
What is Korsakoff's syndrome
chronic condition that is a consequence of Wernicke's encephalopathy.
Neurological Disorder with a thiamine deficiency
90
Symptoms of Korsakoff syndrome
Amnesia
Confabulation
91
What are examples of bilary tract diseases
Biliary colic
Cholecystitis
Ascending cholangitis
92
When does bilary colic ("gallbladder attack") happen
When gallstones get lodged in the bile ducts causing temporary severe abdominal pain
Usually after a fatty meal
93
Risk Factors for developing gallstone
4 F's
Female sex
Age- Forty
Obesity- Fat
Pregnancy - Fertile
94
Clinical Presentation of biliary colic
95
Complication of biliary colic
If gallstone stays in the cystic duct for longer stretches, can lead to acute cholecystitis or inflammation
Can also lead to fever
96
Diagnosis of biliary colic
Based on recurrent symptoms
Confirmed by ultrasound
97
Treatment for biliary colic
Manage pain & other symptoms
Cholecystectomy
98
What is cholecystitis
Inflammation of the gallbladder because of an obstruction of the cystic duct by a gallstone
Most common complication of cholelithiasis (formation of stones in the gallbladder)
99
Define the following terms:
1.Cholelithiasis
2.Choleoocholithiasis
1.Cholelithiasis: Formation of stone in the gallbladder
2.Choleoocholithiasis: Formation of stone in common bile duct
100
What is the difference between the bilary tract diseases:
1.Biliary Colic
2.Acute cholecystitis
3.Cholangitis
1.Biliary Colic: temporary obstruction of the gallstone at the neck of the gallbladder
2.Acute cholecystitis: Gallstone stuck at the cystic duct causing inflammation of the gallbladder
3.Cholangitis: Complication of gallstones where infection develops in the common bile duct. This is life threatening
101
Signs and synptoms of acute cholecystitis
Fever
Nausea
Vomiting
RUQ pain
Pain which may radiate to right side
102
Examination of acute cholecystitis
Postive Murphy's sign
103
What is Murphy's sign
Where a hand is placed at the mid-inferior border of the liver.
The patient is then asked to take a deep breath in. The diahragm lowers during inspiration and with the hand being placed where it is this will irritate the gallbladder as the diaphtagm pushes the gallbladder down.
104
Diff between bilary tract diseases regarding: Pain, Fever, Jaundice
105
Complications of acute cholecystitis
Gallbladder Carcinoid
Chronic cholecystitis
Mucocele
Empyema
Mirizzi's syndrome
Perforation
Gallstone ileus at the terminal ileum
Pancreatitis
Bile backflow -> Obstructive Jaundice
106
What is Courvoisier's Law
Presence of enlarged gallbladder and painless jaundice is u likely due to gallstones rather carcinoma of the head of the pancreas
107
Investigations for acute cholecystitis
Ultrasound is diagnostic
108
Management for acute cholecystitis
Surgery is only done for symptomatic patients
Nill by mouth, IV antibiotic and pain relief is given before surgery
Surgery: Laprocopic cholecystectomy -> Open cholecystectomy
109
Chronic cholecystitis vs Acute Cholecystitis
Acute: Stone lodged in cystic duct/common bile duct -> acute inflammation. 90% is resolved within 1 month
Chronic: Obstruction of cystic duct -> inflammation of gallbladder wall. Constant state of inflammation
110
What is the result of chronic inflammation in chronic cholecystits
Changes gallbladder wall
gallbladder is sensitive -> Pain after meals
Pain is felt in RUQ and right scapula and shoulder
111
Complication of chronic cholecystitis
Porcelain gallbladder
Increase risk of gallbladder cancer
112
Treatment for chronic cholecystitis
Cholecystectomy
113
What is ascending cholangitis?
Acute infection of the bile duct caused by intestinal bacteria ascending from the duodenum
114
Why does flow of bile become blocked in ascending cholangitis
Choledocholithiasis
Stricture
115
Complications of ascending cholangitis
Septic shock
116
Signs and symptoms of Ascending cholangitis
Charcot's triad: RUQ pain, jaundice, fever/chills
Reynold's pentad: Charcot's triad + hypotension/shock, altered consciousness
117
Diagnosis for ascending cholangitis
Blood tests: evidence of infection, jaundice or shock
Medical Imaging: ultrasound, endoscopic retrograde cholangiopancreatography (ERCP)
118
Treatment for ascending cholangitis
119
What are cholestatic liver diseases
Primary sclerosing cholangitis
Primary biliary cholangitis
=both lead to cirrhosis and liver failure
120
What is primary sclerosing cholangitis
Chronic, progressive condition characterised by inflammation and scarring of intrahepatic + extrahepatic bile ducts
121
What is a charactersitc feature in the appearence of bile ducts in primary sclerosing cholangitis
Beads on a string appearance.
This is due to some parts of being unaffected
122
Significance of primary sclerosing cholangitis
Prevalence 6/100,000
2:1 Male to Female
30-40 age peak
80% also affected by IBD (UC)
123
Pathophisiology of primary sclerosing cholangitis
124
Prognosis of primary sclerosing cholangitis
15 years from diagnosis
125
Complications of primary sclerosing cholangitis
1. Cholangiocarcinoma (1/5)
2. Hepatocellular carcinoma
3. Gallbladder malignancy
4. Colorectal cancer
5. Pancreatic cancer
126
Signs and symptoms of primary sclerosing cholangitis
127
Diagnosis of primary sclerosing cholangitis
128
Treatment of primary sclerosing cholangitis
129
What is primary biliary cholangitis
Chronic, progressive autoimmune condition leading to destruction of small intrahepatic bile ducts
130
Significance of primary biliary cholangitis
Prevalence 35/100,000
9:1 Female to male
131
Pathogenesis of primary biliary cholangitis
True autoimmune condition
-F>M
-Association with coeliac's, Sjogren syndrome, thyroiditis
132
Prognosis of primary biliary cholangitis
Slow progression/remission in some cases
Average survival 15-20y from diagnosis
133
What are the complications of primary biliary cholangitis
1.Hepatocellular carcinoma
2.Osteoporosis
134
Signs and symptoms primary biliary cholangitis
135
Diagnosis of primary biliary cholangtitis
136
Treatment of primary biliary cholangitis
137
What is acute pancreatitis
Acute inflammation of the pancreas
10-25% mortality
138
Functions of the pancreas
Endocrine (release into blood)
-Insulin
-Glucagon
-Somatostatin
Exocrine (Secretion via duct)
-Pancreatic Juice: Bicarbonate - neutralises acid. Digestive enzymes - trypsinogen , elastase, lipase, amylase
139
Pathophisiology of acute pancreatitis
Early Activation -> Inflammation -> Oedema -> Vascular Compromise -> Ischaemia -> Necrosis
1) Mild/Interstitial pancreatitis: Inflammation due to cell injury
2) Severe/necrotising pancreatitis: Predominantly necrosis
140
Acute pancreatitis causes
I - idipoathic
G - gallstones (Most common)
E - ethanol (alcohol)
T - trauma
S - steroids
M - microbiological (Mumps, hepatitis, TB)
A - Autoimmune
S - scorpion stings
H - Hypercalcemia, hypertrigylceridemia
E - ERCP, emboli
D- Drugs: Diuretics, gliptins, opiates, VPA, oestrogen
141
Signs and symptoms of acute pancreatitis
1. Abdominal Pain: Epigastric with back radiation. "Band Like"
2. Nausea + Vomiting
3. Fever
4. Loss of appetite
5. Features of Gallstone disease
142
Physical examination in acute pancreatitis
1. Epigastric tenderness
-Rebound tenderness
-Guarding
2. Distension
3. Cullens/Gray Turner signs
-retroperitoneal haemorrhage
Secondary manifestations
Hypovolemia/shock
ARDS
DIC
Multiorgan failure
143
Diagnosis of acute pancreatitis
2/3 of:
1.Abdominal pain
2.Elevated lipase/amylase
3. Indicative imaging findings:
-US/CT
-Imaging more reliable after 48 hours
Other investigations:
Deranged liver function tests
Hypocalcemia - Fat necrosis -> Free fatty acid release -> Bind calcium
Hyperglycemia
144
What is used to predict the severity of pancreatitis
Glasgow Imrie Score: (PANCREAS)
145
What is used to predict the severity of pancreatitis
Glasgow Imrie Score: (PANCREAS)
146
Treatment of acute pancreatitis
Surgery is indicated in some cases:
1. Infected Pancreatic necrosis
2. Non resolving pancreatic pseudocyst
3. Abscess
4. Obstruction
5. Vascular complications
6. Diagnostic uncertainty
147
What is chronic pancreatitis
Persistent, chronic inflammation of pancreas due to autodigestion -> irreversible injury of exocrine, endocrine pancreas
This leads to pancreatic insufficiency & difficulty producing hormones like insulin
148
Causes of chronic pancreatitis
149
Complications of chronic pancreatits
Pancreatic pseudocyst
Ascites
Pancreatic insufficiency
Diabetes Mellitus
Vitamins (ADEK) deficiency
Pancreatic cancer
150
Signs and symptoms of chronic pancreatitis
Severe abdominal pain radiating to back
Nausea
Vomiting
Weight loss
Steatorrhoea
Oedema due to malabsorption
151
Diagnosis of chronic pancreatitis
CT scan
Ultrasound
ERCP/MRCP
Mildly elevated serum amylase,alkaline, phosphatase, bilirubin
152
Treatment for chronic pancreatitis
153
What is ascites?
Abnormal build up of fluid in the peritoneal cavity. Specific 25ml <=
154
What is ascitic fluid made up of
Proteins (Albumin)
Lipids
Bile Acids
WBCs
155
What is SAAG
Serum Ascites Albumin Gradient (SAAG)
Test where we compare the albumin conc in the ascitic fluid with the albumin conc in the serum of the patient
SAAG = Serum Albumin conc - Ascites Albumin conc
High SAAG: >=1.1mg/dL
Low SAAG: <=1.1mg/dL
Useful as it shows whats occuring with the Starling forces bewtween the ascitic fluid and the serum. It shows us whether the imbalance is due to hydrostatic pressure imbalance or oncotic pressure imbalance which are caused by different pathophisiology.
156
Ascites pathophisiology
Ascites with a high serum ascites albumin gradient tells us that fluid is being pushed out of circulation causing an increase in the conc of albumin in the serum because albumin is normally too large to pass through the peritoneum. While the conc in the ascitic fluid is low. Therefore this is a hydrostatic pressure imbalance
Ascites with low serum ascites gradient. Conc of albumin in the ascitic fluid and in serum are similar meaning that the peritoeum is more permeable than usual allowing albumin to pass through. This is an oncotic pressure imbalance
157
Signs and symptoms of ascites
158
Diagnosis of ascites
159
Treatment for ascites
160
What is hepatic encephalopathy
Decline in brain function that occurs as a result of liver failure
161
Pathophisiology of hepatic encephalopathy?
162
What are the causes of hepatic encephalopathy
163
What are the stages of hepatic encephalopathy
West Haven criteria
164
What are the signs and symptoms of hepatic encephalopathy
165
Diagnosis of hepatic encephalopathy
166
Treatment of hepatic encephalopathy
*Depends on type of hepatic encephalopathy*
Grade 3/4 -> Airway protection due to loss of gag reflex
Type A (Acute) : Even Grades 1/2 may require a liver transplant
Type B (Shuntig) : Often resolves spontaneously. Lactulose, rifaximin, vancomycin
Type C (chronic) : Find underlying cause. Often infection
167
What is portal hypertension
Elevated bp in the portal system
Portal hypertension = 5mmHg MORE than inferior vena cava
Normal Range: 5-10 mmHg
168
Causes of portal hypertension
Portal hypertension happens when blood flow from the portal system to inferior vena cava meets resistance
Can be broken down into:
1.Prehepatic
2.Intrahepatic
3.Posthepatic
169
Prehepatic portal hypertension causes
Portal vein thrombosis
Splenic vein thrombosis
AV malformation
Splenomegaly
170
Intrahepatic causes of portal hypertension
Cirrhosis: Alcohol, viral hepatitis, metabolic (Haemachromatosis, Wilson's NAFLD/NASH)
Primary sclerosing cholangitis
Schistosomiasis
Nodular regenerative hyperplasia
171
Posthepatic causes of portal hypertension
IVC obstruction
Right sided heart failure
Budd Chiari syndrome
172
Signs and symptoms of portal hypertension
173
Complications of portal hypertension
1.Variceal Rupture - bleeding
2.Hepatic encephalopathy
3.Ascites
- Spontaneous bacterial peritonitis
- Hepatorenal syndrome
174
Diagnosis of portal hypertension
175
Treatment for portal hypertension
1. Treat underlying cause
2.Reduce portal pressure
-Transjugular intrahepatic portosystemic shunt (TIPS)
3. Prevent complications
-Bleeding: beta blockers, nitrates, terlipressin. Variceal ligation
-Hepatic encephalopathy
-Ascites: Symptatic relief, salt reduction, diuretics, paracentesis
176
What is spontaneous bacterial peritonitis
Ascitic fluid infection
Most common bacterial infection in patients with cirrhosis
Has poor prognosis if missed
177
Clinical presentation of spontaneous bacterial peritonitis (FBI)
Fever
Belly Pain
Increasing Ascites
178
Pathogenesis of spontaneous bacterial peritonitis
Spread of intestinal bacteria into the portal circulation and then ascitic fluid
Most common pathogen is E.Coli
Liver cirrhosis predisposes people to bacterial translocation due to:
1. Bacterial overgrowth
2. Intestinal permeability
3. Acquired Immune deficiency
179
Risk Factors for Spontaneous Bacterial Peritonitis
Varices
Advanced cirrhosis
Prior SBP
Malnutrition
Usage of proton pump inhibitor
180
Investigations for spontaneous bacterial peritonitis
181
Diagnosis of spontaneous bacterial peritonitis
+ SAAG score
182
Management of spontaneous bacterial peritonitis
Ceftriaxone
Albumin
Trimethoprim
183
Metabolic liver disease examples
* Haemochromatosis
* Wilson’s disease
* Alpha 1 antitrypsin deficiency
184
What is haemochromatosis
metabolic disorder where the body absorbs too much iron in the body - iron overload
185
Pathology & Cause of haemochromatosis
186
Types of haemochromatosis
1.Primary (hereditary: autosomal recessive)
2.Secondary (not genetic):
Multiple blood transfusions
Chronic haemolytic anaemias
Excessive iron intake
187
Complications of haemochromatosis
188
Signs and symtpoms of haemochromatosis
189
Diagnosis of haemochromatosis
Lab Results:
High levels of serum iron
Elevated ferritin
High transferrin saturation
Decreased total iron binding capacity
Liver Biopsy
190
Treatment of haemochromatosis
Deferoxamine
Surgery: Advanced liver damage -> transplantation
Phlebotomy
191
What is Wilson's disease
Wilson's disease or hepatolenticular degeneration is a rare autosomal recessive inherited disorder of copper metabolism characterised by excessive deposition of copper in the liver, brain and other tissues
192
Pathogenesis of Wilson's disease
The transport of copper by the P-type ATPase is defective due to one of several mutations (>300 identified) occurring within the ATP7B gene
This gene has been mapped to chromosome 13q14.3
Intestinal copper absorption and transport into the liver are intact, whilst incorporation into caeruloplasmin and excretion into bile are impaired
193
Diagnostic tests of Wilson's disease
194
Management of Wilson's disease
195
Clinical Features of Wilsons disease
196
What is alpha-1 antitrypsin deficiency (liver)
Genetic condition where the alpha-1 antitrypsin gene is defective
197
Clinical presentation of alpha-1 antitrypsin deficiency
198
Dignosis of alpha-a antitrypsin deficiency
Cirrhosis
-Liver Ultrasound
-Liver biopsy: Period Acid Schiif (PAS+). Diastase Resistant
199
Treatment for alpha-1 antitrypsin deficiency
Augmentation therapy
-IV infusion of normal A1AT protein
Slows or halts progression of disease
Standard treatments for cirrhosis
200
Pathology of alpha 1 antitrypsin deficiency
Misfolded alpha 1 antitrypsin builds up, killing hepatocytes and leading to cirrhosis
201
Hepatobiliary cancers examples
Pancreatic cancer (including Courvoisier’s sign)
Hepatocellular carcinoma
Cholangiocarcinoma
202
Pathology and causes of pancreatic cancer
Highly lethal malignancy of exocrine pancreas
Usually unresectable at presentation
203
Risk Factors for pancreatic cancer
204
Symptoms of pancreatic cancer
205
Diagnosis of pancreatic cancer
Medical imaging + biopsy confrim diagnosis
Staging depends on: Size & location
1. less than 2cm
2. greater than 2cm
3. grown into neighbouring tissue
4. metastatic ~ spreads through blood & lymph
206
Treatment for pancreatic cancer
207
Pathology and causes of hepatocellular carcinoma
Hepatic malignancy commonly disagnosed in presence of chronic liver disease
208
Signs and symptoms of hepatocellular carcinoma
209
Risk Factors for developing hepatocellular carcinomas
210
Complications of hepatocellular carcinoma
Paraneoplastic syndrome
Extrahepatic metastasis
211
Hepatocellular carcinoma aetiology
212
Diagnosis for hepatocellular carcinoma
Ultrasound with biopsy, CT scan, MDCT, arteriography, portography, MRI:
Tumour visulaisation, histopathological analysis, grading, TNM staging, potential for resection
MRI angiography
Elevated alpha-fetoprotein (most common serum marker)
213
Treatment for hepatocellular carcinoma
214
Pathology and causes of cholangiocarcinoma
215
Types of cholangiocarcinoma
216
Risk Factors for cholangiocarcinoma
Primary:
Existing liver/gallstone disease, PSC, chronic liver disease
Congenital abnormalities of biliary tree
Genetic disorders
Obesity
Liver Fluke infection
Increasing age
217
Signs and symptoms of cholangiocarcinoma
Abdominal pain
Fatigue
Unintended weight loss
Intensely itchy skin
Jaundice
Changes in colour of stool/urine
218
Diagnosis of cholangiocarcinoma
219
Treatment for cholangiocarcinoma
220
Paracetemol toxicity pharmacology
221
Clinical Presentation of paracetemol toxicity
222
Treatment for paracetemol overdose
223
Diagnosis of paracetemol overdose
+ bilirubin, lipase
- PTT, INR
+BUN, creatinine, ammonia
-Glucose
224
What is Gilbert's syndrome
Benign, genetic condition involving recurrent episodes of jaundice.
It is an unconjugated hyperbilirubinemia
225
Causes of Gilbert syndrome
Autosomal dominant/recessive condition
-70% of cases caused by mutation in UGT gene
Caused by a mild decrease in activity of UDP
226
Clinical Presentation of Gilbert syndrome
227
Treatment and Diagnosis for Gilbert syndrome
228
Diif types of hernias
* Inguinal
* Femoral
* Umbilical
* Incisional
* Epigastric
* Hiatal
229
Inguinal hernias
INGUINAL HERNIA
Protrusion of abdo contents through inguinal canal
Patho
Both direct/indirect present above + medial to pubic tubercle (mostly)
- Direct – 20%, medial to inferior epigastric artery, enters inguinal canal through weakness in posterior wall, rarely strangulates
- Indirect – 80%, lateral to inferior epigastric artery, enters inguinal canal through deep inguinal ring, can strangulate
RFs (risk factors)
Male, chronic cough, heavy lifting, past abdo surgery
Px
Swelling in groin/scrotum
Maybe painful – ‘dragging’ sensation (pain tends to indicate strangulation)
Impulse – swelling increase on coughing
May be reducible
Ix
Clinical dx
Imaging if in doubt (USS/CT/MRI)
Mx
If small, reassure
Surgery (if strangulated, urgent referral)
Truss
230
Femoral hernia
FEMORAL HERNIA
Bowel comes through femoral canal
Patho
Likely to be irreducible and strangulate – due to rigidity of canal’s borders
Px
Mass in upper medial thigh
Neck of hernia inferior and lateral to pubic tubercle (inguinal hernias are superior and medial to this point)
May be cough impulse
Ix
Clinical dx
Imaging if in doubt (USS/CT/MRI)
Mx
Surgical repair
231
Umbilical hernia
At umbilicus
232
Hiatal hernia
HIATUS HERNIA
Herniation of stomach through oesophageal aperture of diaphragm
Patho
- Sliding – (80%), GOJ (gastroesophageal junction) and part of stomach slides up into chest, acid reflux often, LOS (lower oesophageal sphincter) less competent
- Rolling – (20%), GOJ remains in abdo, part of fundus rolls up through hiatus, LOS intact, reflux uncommon
RFs
Obesity, female, pregnancy, ascites, advanced age, skeletal deformities (scoliosis, kyphosis)
Px
Heartburn, especially on lying/bending
GORD
Dysphagia
Ix
CXR
Barium swallow – dx
Upper GI endoscopy if indicated
Oesophageal manometry (mostly used when surgery is being considered)
Mx
Lose weight
PPI
Surgery to prevent strangulation – indications: therapeutic regimes not working, resp complications of reflux, eg asthma
233
Incisional hernias
Tissues or organs protrude through the site of an incision or a scar, which has caused a weakness in the underlying muscle.
234
Epigastric hernias
through linea alba above umbilicus
235
What is the treatment for hernias
Surgery
