Pathophysiology of liver disease Flashcards
liver func
- helpbreak down food > convert into energy and mainatin good balance of glucose levels in blood
- processes waste ammonia»_space; urea
- help right infec.
- create proteins that are responsible for blood clotting (coagulation cascade)
- help body process meds and alcohol
explain liver disease
- build up of scar tissue = damage
- scaring in liver forms irregular bumps that replace smooth liver tissue = liver becomes harder
- scar tissue changes liver’s shape (changes how liver works)
different causes of scar tissue
1.metabolic associated fatty liver disease,
- Alcohol FLD,
- viral infections
- autoimmune liver disease
normal liver look
red
progress from normal liver to a fatty liver; what will it look like?
- greasy
-larger
-harder
-white dropplets (fat droplets/ VENULES) - fat deposits get bigger - nucleus gets pushed out of the membrane (atoptosis)
can become cancerous
fatty liver disease = progression
how is it causes
- “first hit”
- then multiple hits (interlocking processes):
- lipotoxicity
- immune activation
- role of microbiom in background
what is metabolic syndrome?
3-5 conditions
obesity
diabetes
hyperlipidaemia
HTN
REVERSIBLE
Imbalance between what in the liver?
- imbalanace between the fatty acids IN and OUT of liver
- uptake of fatty acids + fatty acid synthesis
^ FA synthesis
^ uptake FFA
dec of FA oxidation
dec lipolysis
dec secretion of FA fro lipoproteins
steatosis
cause fat droplets to from withing hepatocytes
^ synthesis & uptake FFA
dec FA oxidation
dec secretion of FA for lipoproteins
insulin RESISTANCE caused
the gain and loss of fat in teh liver
^of triglycerides
^ in FA
STEATOHEPATITIS - non alcoholic steatohepatitis (metabolic consiquences)
- build up of lipid droplets
- toxic fatty acid metabolites
- ^ in oxidative stress
What happens when processing alcohol?
^ amount of reactive oxygen species in liver =- ^ oxidative stress
unbalanced diet/ not enough antioxidants = excess iun the oxitative stress > take part in cell death
charicteristics of STEATOHEPATITIS (NASH):
hepatocytes are vulnerable to degradation
FA with double bond in carbon chain bind reactive oxygen species which causes damage to lipid membranes e.g. mitochondria
→ inflammation and cell death
Metabolic basis of NAFLD pathogenesis
alter artitecture of liver
Metabolic basis of NAFLD pathogenesis - cirrhosis
scaring beyond repair
having endoplas. reticulum stress
damage atracts neutrophils - stellate cells - activated - lay down fibrotic tissues = SCARRING
(info; can lead to the most common type of cancer = HEPATOCELLULAR CARCINOMA )
Alcoholic fatty liver disease
- 3 million deaths per yr
- have chronic heavy drinking
- no specific lab tests to be done to find it
- liver biopsy - hostory of alcohol abuse
definition of chronic heavy drinking
daily (amount and length) 40-80g a day men/ 20-40g a day women = for 10 years
cirrhosis stage - symptom?
can be tender
shrinkage
bruising easily - break down clotting factors
blood in stool
(sometimes no symptoms)
non -alcoholic liver disease
- NAFLD common causes of chrinci liver dis.
- assoc w obeisty, dyslipidemia and type 2 diabetes mellitus
- diagnosis of NAFLD hepatic steatosis
- liufestyle mods
- no licensed drug treatments
- BUT use of PIOGLITAZONE oir VITAMIN E may be considered for some patients
what happens in alcoholic liver disease:
^ acetyl CoA -= ^ FA
^ NADH = dec in metabolism ^ FA
dec NAD+ - dec FA oxidation
dec synthesis of lipoproteins
^ peripheral lipolysis
Non-alcoholic liver disease
- ^ dietary fats, ^ fructose intake
- ^ hepatic lipase uptake FFA
^ storage of FFA and TG
dec secretion of lipoproteins
dc FA secretion
Metabolic consequences of heavy ethanol consumption
↑Acetaldehyde ↑ reactive oxygen species
Excess NADH result in:
Anion gap metabolic acidosis
Lactic acidosis
Ketoacidosis
Fasting hypoglycemia
impaired gluconeogenesis
inhibition of TCA cycle
Hepatosteatosis
STOP DRINKING
Metabolic consequences of fructose consumption
Insulin resistance ↑ lipogenesis ↑ oxidative stress and inflammation and is often potentiated by genetic and gut microbiome dysfunction
What rae the Harmful effects of acetaldehyde on ALD?
The liver metabolizes ethanol:
Alcohol dehydrogenase (ADH)
Cytochrome p450
Catalase in peroxisomes
hypothyroidism
dec in FT4/FT3
^ TSH
what does hypothyroidism cause?
^ lipolysis
dec triglycerides clearance
hepatic accumulation of triglycerides
insulin resistance
lopogenesis
storage of free fatty acids in liver
^ TBF and leptin
dec of mitochondrial turnover
dec adiponectin hepatic inflammation and fibrosis
dec of bile acid flow
