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
Describe Hep B serology results
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
