Liver Flashcards
Describe ethanol metabolism
ADH = alcohol dehydrogenase in this case
MEOS = microsomal ethanol oxidising system
Describe paracetamol metabolism
2 pathways:
Phase 1:
- Gluconuride/ Sulfate metabolites
- NAPQI (Toxic)
Phase 2:
- Gluconuride metabolites & sulfate metabolites are excreted renally
- NAPQI is metabolised by Glutathione before it can be excreted renally
In paracetamol overdose, Glutathione is depleted, leading to NAPQI buildup causing hepatocyte necrosis
“Think when hes Naccered”
N-Acetyl-Cystiene (NAC) Rx for overdose binds to NAPQI.
Also increases synthesis and availability of glutathione
Describe the impacts of chronic alcohol consumption
- Upregulation of MEOS system
- Cytochrome p450 enzyme is a component MEOS, and its consumption in ETOH metabolism impacts the bodies ability to metabolise drugs, toxins, fatty acids
Describe net impacts of alcohol metabolism, specifically
via Alcohol DeHydrogenase / ADH - pathway
↓ NAD+ : ↑ NADH
↑ Acetate
Low NAD+ : Prevents fatty acid oxidation, impacts on glycolysis
High NADH: Inhibits lactate conversion to pyruvate (lactic acidosis risk), Inhibits key TCA enzymes thus accumulation acetly-CoA
Describe fatty changes in AUD (Alcohol Use Disorder) livers
- ß-oxidation of fatty acids is inhibited
- acetyl-CoA is a precursor for fatty acid
biosynthesis
Thus triglycerols accumulate in hepatocyte cytoplasm
- Combo ↑ MEOS upregulation, thus ↑ ROS, & ↑ lipid peroxidation -> hepatocellular damage
Describe bilirubin metabolism and excretion
- Macrophages in spleen and bonemarrow phagocytose and degrade erethyrocytes (RBCs)
- Release haemoglobin which is broken down into both: haeme and globin
- Globin - essentially protein, broken down into amino acids and recycled (think globe - round, recycling
- Haeme - Unconjugated Bilirubin and Iron (Fe2+) - Iron stays in circulation and mostly recycled, but unconjugated bilirubin is toxic and must be excreted
- Unconjugated Bilirubin is Hydrophobic thus it is carried in the blood by Albumin protein
- Unconjugated Bilirubin is carried to the liver and conjugated to hydrophilic Glucoronic Acid to make it water soluble
- Conjugated bilirubin is secreted with Bile into the duodenum, passes along digestive tract and is converted by intestinal bacteria to Urobilinogen
-
10-15% of Urobilinogen is reabsorbed by blood in portal system.
~ Half of this involved in Enterohepatic Bilinogen cycle and is resecreted by hepatocytes into bile
~ Remaining half travels to kidneys via blood, is converted to Urobilin and excreted in urine, giving it the distinct yellow colour - 85-90% of remaining Urobilinogin is oxidised by intestinal bacteria to Stercobilin
- Stercobilin is excreted in Feces, giving it brown colour pigment
Kupffer cells are:
Fixed macrophages of the liver
Found in sinusoids
Produced in blood, circulate as monocytes before entering tissue
Mallory bodies are:
Mallory hyaline -> deposits of altered cytoskeletal filaments in damaged hepatocytes
Common in alcoholic steatohepatitis
Rx for Paracetamol overdose
- Activated charcoal - taken within 1 hour
- If paracetamol intake is in excess of 150mg/kg, or 12g -> whichever smaller
- Think - 60kg = 9g, 80kg = 12g
- Acetylcystiene and methionine - protect liver if given within 10-12 hrs of ingestion
- Acetylcystiene effective up to, and maybe > 24hrs
Most common locations of renal stone lodging
- Pelvo-ureteric junction
- Ureter passing over pelvic brim
- Vesicouriteric junction
- PUJ - UJ - VUJ
Most 4 common type of pelvic stones & causes
Calcium oxalate - Hypercalcuria + hyperoxaluria
Uric Acid - Hyperconcentration of urine
Struvite - NH4+ producing bacteria
Cystiene - Congenital
What is the pathophysiology of alcohol abuse leading to cirrhosis?
- High alcohol intake leads to the upregulation of the MEOS pathway
- This leads to an increase in ROS and NADH as metabolites
- ROS increase -> hepatocellular injury
- NADH increase -> inhibition of kreb cycle and lypolysis - leads to fat deposition in liver
- > Steatohepatitis
- Stellate cells consume excess lipids -> this leads to fibrosis
- Scar tissue replaces normal parenchyma, leads to blockage of portal blood flow
Fibrosis -> Sclerosis -> Cirrhosis
Pathophys of hepatic encepalopathy
- Cirrhosis leads to portosystemic shunt
- This leads to insufficient metabolism of NH3
- Increased glutamine and NH3 leads to cerebral oedema, and increased intracranial pressure
- Increased intracranial pressure and an increase of neurotoxins leads to encepalopathy
Causes of hepatomegaly
Massive
- Hepatocellular cancer
- Metasteses
- ALD (alc liver disease) with fatty infiltration
- R heart failure
Mod
- Above
- Haemochromatosis
- Haematological diseases - eg chronic leukaemia, lymphoma
- NAFLD (non alc fatty liver disease) -> 2ndary to diabetes, obesity, toxins
Mild
- Above
- Hepatitis
- Billiary obstruction
- Human immunodeficiency virus (HIV)
Causes of gallbladder enlargement
With jaundice
- Carcinoma head pancreas
- Carcinoma amupulla of vater
- In situ gallstone - common bile duct
Without jaundice
- Mucocele (distended gallbladder filled with mucus or watery content) of GB
- Empyema (pocket of pus) of GB
- Carcinoma of GB - stone hard, irregular swelling
- Acute cholycystitis
Causes of hepatosplenomegaly
- Chronic liver disease with portal hypertension
- Haematological disease (lymphoma, leukaemia, pernicious anaemia, sickle cell anaemia)
- Infection (acute viral hepatitis, infectious mononeucleosis, cytomegalovirus)
- Infiltration (amyloid, sarcoid)
- Connective tissue diseases (systemic lupus, erythematosus)
- Acromegaly
- Thyrotoxicosis
Describe Hep B serology results
Cytochrome P450 enzymes are involved in:
Phase one reactions which are mostly oxidation reactions
Not phase 2 conjugation reactions
The “portal triad” is surrounded by the hepatoduodenal ligament.
What does the triad consist of?
- Hepatic Artery
- Portal Vein
- Bile duct
What do gallstones most likely consist of?
What is the fancy name for them?
Calcium bilirubinate - can less commonly consist of cholesterol or mix
Cholelithiasis - presence of gallstones or any disease caused by them
Explain what is “Fasciola hepatica”
“Common liver fluke” or “sheep liver fluke”
Disease is called “facsciolosis” or “fascioliasis”
Clinical pattern of Hep A
- Faecal oral route
- More common in young children and contacts - parents, teachers etc
- Prodromal (initial onset developing symptoms) - Malaise, flu like symptoms
- Deep jaundice
- Dark urine, pale stools
Describe “Infectious Mononucleosis”
Aka - Glandular fever or “Mono”
Usually caused by Epstein-Barr-Virus (EBV)
Few or no symptoms in children
As adult
- Fever, malaise,
- Swollen lymph nodes in neck
- Tonsils/Fauces swollen and with exudate
- Can have hepatomegaly or splenohepatomegaly - assoc hepatitis
2 major ketone body byproducts of FFA metabolism during hypoglycaemia (or insufficeint insulin)
B-hydroxybutyrate
Aceto-acetate
(both from Acetyl-COA)
Summarise steps - inputs/outputs of ketogenesis
Ketone bodies mostly produced in mitochondria of hepatocytes in response to unavailability of blood glucose due to:
- Insufficient carbohydrate intake
- Periods of fasting/ starvation
- Poorly managed diabetes
