Liver, Biliary And Pancreatic conditions, Signs, Causes And Differentials Flashcards
What are the two classifications of conjugated hyperbilirubinaemia? (Not unconjugated, which is prehepatic)
Hepatocellular
Obstructive
What are the causes of obstructive jaundice?
Carcinoma of the pancreas head
Cholangiocarcinoma
Gallstones in duct* (or cholangitis/cholecystitis could cause this)
Sclerosing cholangitis
Lymph node metastases
Chronic pancreatitis
*stones in gall bladder cause no obstruction
Why does obstructive jaundice cause prolonged PT and APTT?
Obstruction of flow of bile causes reduced absorption of the fat soluble vitamins: D, E, A, K
Vitamin K is essential for the production of factors 2, 7, 9 and 10
When these factors aren’t produced, the intrinsic and Extrinsic coagulation mechanisms are inhibited, therefore bleeding time goes up
What are the causes of hepatocellular jaundice?
Viral hepatitis
Alcoholic hepatitis
Cirrhosis
Drug induced hepatocellular damage
Non-alcoholic fatty liver disease
Wilson’s disease (excess copper deposition)
Haemochromatosis (iron overload)
Autoimmune hepatitis
What are differentials for Jaundice with abdominal pain?
Cholangitis (RUQ pain + fever)
Pancreatitis (Epigastric pain radiating to back)
Gallstones (RUQ pain + fever)
Or gallstones in the bile duct (Epigastric pain radiating to back)
First thing you should think about in the case of jaundice with no abdominal pain?
Cancer of the pancreas, or liver, or anywhere in the biliary tree
Cholangiocarcinoma
Hepatocellular carcinoma
Hepatoblastoma
Cancer of the head of the pancreas
Signs of hepatobiliarypancreatic cancer?
Unintentional weight loss
Cachexia
Hard lymphadenopathy
Craggy liver edge
What are the four main cancers of the biliary system?
Carcinoma of the head of the pancreas (most common)
Primary hepatocellular carcinoma
Liver cancer as a metastasis
Cholangiocarcinoma
What are the signs of alcohol poisoning?
Confusion
Vomiting
Loss of coordination
Stupor (unresponsive)
Hypothermia
Bradypnoea
Seizures
Cyanosis
What is delirium tremens?
An acute confusional state due to stopping a chronic drinking habit (alcohol withdrawal), the worst presentation of alcohol withdrawal syndrome.
Characterised by signs of overactivity in the SNS.
Caused by abrupt decrease in ethanol level causing an imbalance of excitatory signals in CNS.
The NMDA receptors were upregulated and the GABA receptors downregulated during alcoholism, since alcohol did the work of the inhibitory pathways.
What are the signs of delirium tremens?
Confusion
Tremor
Anxiousness
HTN
Tachycardia
Insomnia
Irritability
Diaphoresis (sweating)
Headache
Hallucination
How long must you have the signs of liver inflammation to be diagnosed with chronic hepatitis?
6 months
What signs are specific to obstructive causes of hyperbilirubinaemia?
Pale stools
(no secretion in to bowel via biliary tree so no urobilinogen formed and so no stercobilogen production)
Dark urine
(increased bilirubin excreted, no urobilinogen)
Itching
(Associated with obstructive jaundice)
What is cirrhosis?
Fibrotic irreversible liver damage with regenerative nodules surrounded by fibrotic proteins.
Activation of stellate cells.
Loss of vitamin A
Production of TGF-Beta
- collagen formation occurs
Scar tissue builds up Compression of sinusoids, portal veins and hepatic arteries - portal hypertension - liver has lost functional units -decreased detoxification ability
What are the signs of acute hepatitis?
Malaise
Jaundice
RUQ pain (inflamed liver presses on Gleason’s capsule)
Severe acute hepatitis:
Confusion
Coagulopathy (increased INR and falling albumin indicates function is failing)
What are the signs of chronic liver disease?
Jaundice
Hepatomegaly
Spider naevi
Palmar erythema
Portal hypertension
In a patient who begins drinking, which disease states can their liver go through before cirrhosis?
Normal liver > Fatty liver > Steatohepatitis > Alcoholic hepatitis > Cirrhosis
Or patient can go directly:
Normal liver > Alcoholic hepatitis > Cirrhosis
What is a fatty liver?
An inflamed liver, due to proinflammatory effects of viruses, drugs, alcohol and other causes.
What is steatohepatitis?
An inflamed liver with fibrous tissue laid down within it. (Like a pre-scar)
What are the symptoms of compensated cirrhosis?
Can be asymptomatic for up to ten years
What are the causes of haemolytic jaundice?
Sickle cell anaemia
Incompatible blood transfusion (immune attack)
Hypersplenism (overactive spleen, not the same as splenomegaly)
Drug reactions
Which liver enzyme is saturated in haemolytic jaundice?
Glucoronyl transferase
Glucoronyl transferase only reaches peak function at 40 weeks gestation.
Which two symptoms distinguishes haemolytic jaundice and obstructive jaundice?
Dark stools and normal urine = Haemolytic
White stools and dark urine = Obstructive
Excess unconjugated bilirubin in serum can’t enter urine unless they are conjugated: unconjugated bilirubin is NOT water soluble.
Dark stools occurs because the GT enzyme is fully saturated due to excess unconjugated bilirubin, therefore max stercobilinogen present.
If obstruction occurs conjugated bilirubin enters blood and darkens urine, but cannot enter intestine to colour stools.
Which will rise in obstructive jaundice: ALP or ALT/AST?
ALP rises (ALT and AST will rise too but less than the rise in ALP)
The cystic/bile ducts are the bigger source of ALP
The liver itself is the biggest source of ALT/AST because they are conjugation enzymes
What is neonatal jaundice?
A very common condition (2/3 of all term babies, and 4/5 of all preterm)
Caused by low GT liver enzyme function.
Glucoronyl transferase only reaches peak function at 40 weeks gestation.
What is kernicterus?
Toxic yellowing of the brain.
Caused by unconjugated bilirubin crossing the BBB.
What signs and symptoms should you look for in a patient presenting with jaundice?
Presence of pain
Duration and any fluctuation
Scratches (itching from hyperbilirubinaemia)
Colour of urine and stools
Weight loss
Troisiers node (left supraclavicular)
Organomegaly
Fever
Spider naevi (oestrogen, non-blanching)
Palmar erythema (oestrogen)
Portal hypertension (Caput medusa, oesophageal/rectal varices)
Ascites (low albumin and portal hypertension)
Flapping tremor (encephalopathy)
Confusion (encephalopathy)
Vomiting (encephalopathy)
Fits (encephalopathy)
In a patient presenting with RUQ pain, which parts of their anatomy could be the cause?
Liver
Diaphragm
Gall bladder
Kidney
Bile duct
Duodenum
Pancreas
What are the differentials for RUQ pain?
Acute pancreatitis
Perforated viscera
Cholangitis/biliary colic
Pyelonephritis/renal colic
Acute mesenteric ischemia (emboli or thrombus)
Pneumonia
MI
What are the causes of hepatic encephalopathy?
Alcohol (binge drinking or quitting drinking)
Opioids
GI haemorrhage (causes increased ammonia production)
Increased protein intake (causes increased ammonia production)
Hypoglycaemia
Renal failure
Infection
Constipation
How is hepatitis A spread?
Faecal-oral spread
Associated with high risk countries and poor hygiene.
How is hepatitis B spread?
Blood
Sex
Maternal transmission
How is hepatitis C spread?
Blood (most common)
Sex
Maternal transmission
What are the risk factors for hepatitis B infection?
IVDU
Medical treatment with contaminated equipment
Maternal infection
Travel to Africa and Asia
What are the risk factors for hepatitis C infection?
IVDU
Medical treatment with unhygienic equipment
Tattoos
Sharing razors or toothbrushes
Who is more likely to develop chronic hepatitis B infection, a newborn or a 5 year old ?
The newborn.
< 1 years old = 90% chance of chronicity
5+ years old = 1-5% chance of chronicity
How is hepatitis E spread?
Faecal-oral route
How is hepatitis A spread?
Faecal-oral spread
Associated with high risk countries and poor hygiene.
How is hepatitis B spread?
Blood
Sex
Maternal transmission
How does hepatitis C normally present?
Asymptomatic (there is no fulminant stage)
Later in life as cirrhosis
What are the portal hypertension signs of cirrhosis?
Most often ASYMPTOMATIC
Portal hypertension:
- Caput medusa
- Ascites
- Piles
- Splenomegaly
- Encephalopathy (less blood through liver means less toxins removed)
- Renal failure (reduced return to kidney meaning RAAS system will constrict eff arteriolar and caused acute kidney injury)
What are the hepatic dysfunction signs of cirrhosis?
Hepatic dysfunction:
1. Jaundice
- Decreased drug metabolism (increased effects)
- Atrophic testes and body hair loss (Decreased hepatic hormone production/metabolism)
- Palmar erythema, Spider naevi and gynaecomastia (increased oestrogen)
- Bruising (coagulopathy)
- Hypoalbuminaemia
- Leukonychia (hypoalbuminaemia)
- Clubbing (any fibrotic change in body does this)
- Dupuytren’s contracture (signs of alcohol excess)
- Xanthelasma (sign of lipid disregulation)
- Hepatomegaly (initially, then in later stages the liver shrinks)
- Asterixis (encephalopathy)
What are the signs of hepatic failure?
Bruising and spontaneous haemorrhaging (Coagulopathy)
Confusion and coma (encephalopathy)
Oedema (hypoalbuminaemia)
Increased sepsis risk (liver lymphoid function is normally very important)
Hypoglycaemia (no glycogen storage in liver)
Spontaneous bacterial peritonitis
What are the signs of alcohol withdrawal syndrome?
AWS, Not delirium tremens
Tachycardia
Hypotension
Tremor
Confusion
Fits
Hallucinations
Nausea and vomiting
What are the signs of delirium tremens?
Severe confusion
Agitation
Irritability
Seizures
Hallucinations
Mood changes (depression, anxiety)
Restlessness
Stupor
Fatigue
Insomnia or fatigue
Sensitivity to light, touch or sound
Body tremors
How long after the final drink do the signs of alcohol withdrawal syndrome (or delirium tremens) begin?
10 to 72 hours after the final drink
What are the infective causes of acute hepatitis?
Hepatitis viruses A, B and E
Epstein-Barr virus
Cytomegalovirus
What are the main lifestyle factors that contribute to acute hepatitis?
Obesity
Diabetes mellitus
Alcohol excess
Which drugs can cause acute hepatitis?
Antiepileptics
Rifampicin (antibiotic)
Flucloxacillin
Methotrexate
Paracetamol (as o/d)
What are the autoimmune causes of acute hepatitis?
Autoimmune hepatitis (a condition where the liver’s own immune system attacks itself)
Primary biliary cholangitis
Primary sclerosing cholangitis
What are the hereditary causes of acute hepatitis?
Hereditary haemachromatosis
Wilson’s disease
Alpha-1 antitrypsin deficiency
How does alcohol cause alcoholic liver disease to occur?
Increased acetaldehyde (causes inflammation)
Upregulates P4502E1 (produces ROS > necrosis)
Increased hepatic macrophage activity (produces ROS > necrosis)
Inhibition of gluconeogenesis by NADH (due to NADH byproduct of ethanol conversion to acetaldehyde), and subsequent fatty acid oxidation, freeing fatty acids that infiltrate the liver
What are the signs of alcoholic liver disease?
Common:
RUQ pain
Hepatomegaly
Haematemesis
Ascites
Weight change
Anorexia
Fatigue
Uncommon:
Melaena
Splenomegaly
Jaundice
Palmar erythema
Asterixis
What is acute pancreatitis?
Sudden inflammation of the pancreas that is self-limiting and reversible.
MOA: zymogen granules activate before exiting the pancreas and autodigest the organ.
What are the risk factors for acute pancreatitis?
Heavy alcohol use
Gallstones
Abdominal trauma
Steroids
Infections
Tumours
High triglycerides
Hypercalcemia
What are the three main causes of acute pancreatitis?
Alcohol (40%)
Gallstones (40%)
Idiopathic
Other: trauma, steroids, mumps, autoimmune, scorpion/spider venom, Hyper-lipidemia/calcemia/parathyroidism, ERCP, drugs
What are the signs of acute pancreatitis?
Sudden epigastric pain radiating to back (can be in hypochondriac regions)
Episodic
Nausea
Vomiting
Tachycardia
What is chronic pancreatitis?
Recurrent/persistent, progressive injury to the pancreas with associated abdominal pain.
MOA: Inflammation causes scarring and loss of pancreas function.
e.g. alcohol damages acinar cells causing inflammation and membrane destruction, leading to pancreatic calcifications
What are the threetypes of chronic pancreatitis according to the Sarles classification?
Obstructive pancreatitis
Inflammatory pancreatitis
Lithogenic or calcifying chronic pancreatitis.
What are the signs of chronic pancreatitis?
Sudden epigastric pain radiating to back (can be in hypochondriac regions)
Episodic
Nausea
Vomiting
Tachycardia
Steatorrhoea
Brittle diabetes
Weight loss
Bloating
What can cause decompensation of a stable liver cirrhosis?
Hypoglycaemia
GI bleed
Infection
Alcoholic binge
What is diabetes mellitus?
Reduction in insulin action sufficient to cause a level of hyperglycaemia that over time, will result in diabetes specific microvascular pathology of the eyes, kidneys and nerves.
Oral glucose test = >11.1 mol/L
Or, Fasting glucose = >7 mol/L
What is non-diabetic hyperglycaemia?
Insulin action is reduced such that blood glucose is raised but not to a level that will cause microvascular damage.
Oral glucose test = 7.8-11.1 mol/L
(AKA: prediabetes, impaired glucose tolerance, impaired fasting glucose)
At what age is diabetes onset most likely type 2 than type 2?
Age 30 (after this, it’s more likely T2)
How does diabetes type 2 originate?
Pretty much it’s fats making the liver and pancreas not store glucose and create insulin at the right moment.
- Positive calorie diet
- Increased VLDL triglycerides
- Storage of fat in liver = Resistence to insulin suppression of hepatic glucose production = increased glucose production
- Deposition of fat in islet cells = affects glucose sensing equipment = Decreased insulin release in response to food
- Increased basal plasma glucose = increased basal insulin release - peaks in prediabetes stage
Other than type 1 and 2, what other types of diabetes mellitus are there?
Maturity onset diabetes mellitus if the youth (MODY)
Exocrine pancreas disease - DM due to pancreatitis
Endocrinopathies - Cushing
Drug induced - antipsychotics and corticosteroids
Post-transplant
Which sensation is lost in peripheral neuropathy before all others?
Vibration
What are the three components of metabolic syndrome?
Central obesity
Diabetes mellitus
Hypertension
What are the signs of diabetic ketoacidosis/hyperosmolar hyperglycaemic state?
(Same signs in both)
Signs of diabetes: polyuria, polyphagia, polydipsia, weight loss, weakness, sunken eyes
Hyperventilation (respiratory compensation)
Nausea and Vomiting
Abdominal pain
Dehydration
Hypotension
Decreased GCS
On investigation: Hyperkalemia Glycosuria (or ketonuria DKA) Leucocytosis Hyperlipidaemia Raised creatinine
How does diabetic ketoacidosis happen? What is the physiological process?
- Decreased insulin means that the catabolic effects of other hormones (glucagon etc) aren’t balanced out
- Therefore glucose levels build even higher but the body cannot use them without insulin.
- The liver begins to break down fats to form free fatty acids, this generates ketones
- Ketones are acidic, so this produces a metabolic acidosis
What are the most common causes of hypoglycaemia?
Insulin
Sulphonylureas
Meglitinides
Less common causes: ExPLAIN
Exogenous drugs (as above) Pituitary insufficiency Liver failure Addison’s disease Islet cell tumours Non-pancreatic neoplasms
What are the signs of hypoglycaemia?
Adrenergic and neuroglycopenic
Adrenergic:
Sweating
Trembling
Hunger
Neuroglycopenic:
Parasthesiae
Blurred vision
Confusion
Hunger is the first sign.
What is Whipple’s triad?
A trio of signs that indicate a hypoglycaemic state is pancreatic in origin.
- Signs of hypoglycaemia
- Plasma glucose is below 3.1mmol/L
- Symptoms improve on giving glucose
What is hypoglycaemia?
Blood glucose <3.1 mol/L
What are the differentials for hyperosmolar hyperglycaemic state (and DKA)?
Lactic acidosis
Starvation ketosis
Alcoholic ketoacidosis
Poisoning
Uraemia acidosis
What are the signs of type 2 diabetes mellitus?
May be Asymptomatic
Hyperglycaemia: (primary cause of signs)
- Polydipsia
- Polyuria
- Nocturia
- Polyphagia
- Fatigue
- Weight loss
- Blurred vision (hyperglycaemia)
Present as an emergency:
Hyperosmolar hyperglycaemic state
- Hyperventilation, altered mental status, tachycardia, dry mucous membranes, hypotension, N&V
Present with complications:
Neuropathy - diabetic foot ulcer Retinopathy - visual field loss, Nephropathy Cellulitis Skin abscess Cystitis Pyelonephritis Vaginal/penile Candida infection ACS Stroke PVD
What are the signs of type one diabetes mellitus?
- Polydipsia
- Polyuria
- Nocturia
- Fatigue
- Weight loss
- Blurred vision
What are the pathological processes that occur in the eye to cause diabetic retinopathy?
Hyperglycemia causes an over saturation of the sorbitol to fructose pathway, depletes NADH necessary to this step.
Increased sorbitol = (impermeable to membrane) causes osmotic damage to retinal cells.
Formation of advanced glycation endproducts (from reaction of glucose with amino acids) damages blood vessels and nerves.
Capillary leakage > intraretinal haemorrhage > oedema > hard exudates, If in macula > loss of central vision
Capillary occlusion > retinal ischemia > angiogenesis > glaucoma/retinal detachment/vitreous fibrosis
What are differentials for pain in the lower limbs?
Peripheral vascular disease - first signs are claudication of the lower limbs
Gout
Osteoarthritis
What is haemachromatosis?
A genetic condition caused by mutation of the haemochromatosis gene HFE.
HFE modulates expression of hepcidin (hepatic iron-regulatory hormone).
Low hepcidin expression occurs, which means:
- duodenal iron absorption is uninhibited
- macrophages continually release iron from erythrophagocytosis (spleen)
This results in elevation in serum iron and transferrin saturation, and deposition of iron in multiple organs; liver, heart, anterior pituitary, pancreas, joints and others.
The iron is an oxidant, which causes fibrosis, and can also cause bronze diabetes (pancreas damage).
Types:
Hereditary - >90% autosomal recessive, white people only
Juvenile - presents in 20/30’s, with cardiomyopathy and hypogonadism
Transferrin receptor 2 - rare
Ferroportin disease -
What are the signs of haemochromatosis?
Fatigue
Weakness
Arthralgia
Hepatomegaly
DM
Impotence (Male)
Skin pigmentation
What is ascending cholangitis?
This is the acute infection of the common bile duct caused by obstruction, most commonly caused by gall stone, this inflammation ascends towards the liver.
What is primary biliary cholangitis?
A chronic autoimmune disease of the small bile ducts within the liver (intrahepatic), causing inflammation and damage.
What is primary sclerosing cholangitis?
An autoimmune inflammation of the medium and large biliary ducts, this affects the area in between the intrahepatic ducts (primary biliary cholangitis)and the large biliary ducts (ascending cholangitis).
What is cholecystitis?
Inflammation of the gall bladder due to gall stone obstruction of the GB or the GB neck.
