Pathophysiology of liver disease

Question 1

liver func

Answer 1

1. helpbreak down food > convert into energy and mainatin good balance of glucose levels in blood
2. processes waste ammonia&raquo_space; urea
3. help right infec.
4. create proteins that are responsible for blood clotting (coagulation cascade)
5. help body process meds and alcohol

Question 2

explain liver disease

Answer 2

• 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)

Question 3

different causes of scar tissue

Answer 3

1.metabolic associated fatty liver disease,

2. Alcohol FLD,
3. viral infections
4. autoimmune liver disease

Question 4

normal liver look

Answer 4

red

Question 5

progress from normal liver to a fatty liver; what will it look like?

Answer 5

• greasy
  -larger
  -harder
  -white dropplets (fat droplets/ VENULES) - fat deposits get bigger - nucleus gets pushed out of the membrane (atoptosis)

can become cancerous

Question 6

fatty liver disease = progression

how is it causes

Answer 6

1. “first hit”
2. then multiple hits (interlocking processes):
   - lipotoxicity
   - immune activation
   - role of microbiom in background

Question 7

what is metabolic syndrome?

Answer 7

3-5 conditions

obesity
diabetes
hyperlipidaemia
HTN

REVERSIBLE

Question 8

Imbalance between what in the liver?

Answer 8

• imbalanace between the fatty acids IN and OUT of liver
• uptake of fatty acids + fatty acid synthesis

Question 9

^ FA synthesis

Answer 9

^ uptake FFA
dec of FA oxidation
dec lipolysis
dec secretion of FA fro lipoproteins

Question 10

steatosis

Answer 10

cause fat droplets to from withing hepatocytes

^ synthesis & uptake FFA

dec FA oxidation
dec secretion of FA for lipoproteins

Question 11

insulin RESISTANCE caused

Answer 11

the gain and loss of fat in teh liver
^of triglycerides
^ in FA

Question 12

STEATOHEPATITIS - non alcoholic steatohepatitis (metabolic consiquences)

Answer 12

• build up of lipid droplets
• toxic fatty acid metabolites
• ^ in oxidative stress

Question 13

What happens when processing alcohol?

Answer 13

^ amount of reactive oxygen species in liver =- ^ oxidative stress

unbalanced diet/ not enough antioxidants = excess iun the oxitative stress > take part in cell death

Question 14

charicteristics of STEATOHEPATITIS (NASH):

Answer 14

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

Question 15

Metabolic basis of NAFLD pathogenesis

Answer 15

alter artitecture of liver

Question 16

Metabolic basis of NAFLD pathogenesis - cirrhosis

Answer 16

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 )

Question 17

Alcoholic fatty liver disease

Answer 17

• 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

Question 18

definition of chronic heavy drinking

Answer 18

daily (amount and length) 40-80g a day men/ 20-40g a day women = for 10 years

Question 19

cirrhosis stage - symptom?

Answer 19

can be tender

shrinkage

bruising easily - break down clotting factors

blood in stool

(sometimes no symptoms)

Question 20

non -alcoholic liver disease

Answer 20

• 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

Question 21

what happens in alcoholic liver disease:

Answer 21

^ acetyl CoA -= ^ FA
^ NADH = dec in metabolism ^ FA
dec NAD+ - dec FA oxidation
dec synthesis of lipoproteins
^ peripheral lipolysis

Question 22

Non-alcoholic liver disease

Answer 22

• ^ dietary fats, ^ fructose intake
• ^ hepatic lipase uptake FFA
  ^ storage of FFA and TG
  dec secretion of lipoproteins
  dc FA secretion

Question 23

Metabolic consequences of heavy ethanol consumption

Answer 23

↑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

Question 24

Metabolic consequences of fructose consumption

Answer 24

Insulin resistance ↑ lipogenesis ↑ oxidative stress and inflammation and is often potentiated by genetic and gut microbiome dysfunction

Question 25

What rae the Harmful effects of acetaldehyde on ALD?

Answer 25

The liver metabolizes ethanol:
Alcohol dehydrogenase (ADH)
Cytochrome p450
Catalase in peroxisomes

Question 26

hypothyroidism

Answer 26

dec in FT4/FT3
^ TSH

Question 27

what does hypothyroidism cause?

Answer 27

^ 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