Liver Flashcards
Functions of liver
• metabolism • immunity • storage • detox • synthesis • catabolism • activation • transport • excretion Miss CATED
Liver metabolic processes
- Carbohydrate
- Lipid
- Protein
Liver Carbohydrate metabolic process
- stores glucose as glycogen
- glycogenolysis in fasting
- gluconeogenesis in fasting
Liver lipid metabolic process
- synthesis of cholesterol
* lipoproteins - VLDL, LDL, HDL
Liver protein metabolic process
- a.a synthesis
* breakdown of a.a to ammonia and then urea for excretion.
Liver detox ammonia
- harmful ammonia to urea.
* major elimination route of nitrogenous waste
Liver detox drugs
- Phase I reactions - CYP450
- Phase 2 reactions - conjugation with other compounds to become more hydrophyllic
- Age, nutrition and genetics influence drug metabolism
Liver Phase 1 detox
CYP450
Liver Phase 2 detox
conjugation w other compounds to become more hydrophyllic eg gluconosyltransferases
Endocrine activities of liver
- modification of some hormones
* major organ for degradation of hormones
Modification of some hormones
- vitD3 to 25-OH vit D3
- Thyroid hormone - convert T4 to more potent T3
- Insulin-like growth factors produced by hepatocytes modify action of growth hormone
Major organ for degradation of hormones
- insulin and glucagon
- oestrogens, glucocorticoids, growth hormone, PTH
- gastrin and other GI hormones (kidney degrades more of these)
Storage in Liver
- fats
- glycogen
- trace elements - Cu,Fe
- vitamins - A,D,K
Synthesis in Liver
- hormones
* plasma proteins
Hormone synthesis in liver
- insulin-like growth factor
* Thrombopoietin - stimulates platelets
Plasma protein synthesis in liver
- Coagulation factors
- transport for cholesterol (lipoproteins)
- transport for steroid and thyroid hormones
- Angiotensinogen - salt conservation
Iron transport and metabolism protein synthesis in liver
Transferrin, heptaglobin, hemopexin, hepcidin
Acute phase protein synthesis in liver
Important in inflammation
Bile acid synthesis in liver
- 1º - cholic acid and chenodeocycholic acid
* 2º - deoxycholic acid and lithocholic acid
1º Bile acid synthesis in the liver
Cholic acid and chenodeoxycholic acid
2º Bile acid synthesis in liver
deoxycholic acid and lithocholic acid
What is bile?
(Aq) alkaline fluid containing: • Bile salts • Cholesterol • Lecithin • Bilirubin
Where bile stored?
Stored & concentrated in gall bladder
Bile secreted by?
liver.
• actively diverted to gallbladder between meals.
After meal, bile enters?
duodenum
Bile salts are?
derivatives of cholesterol
Bile salts - function?
Convert large fat globules into liquid emulsion
Bile salts once function over
Most reabsorbed into blood.
Micelle structure
- Cholesterol center - all lipid soluble
- Hydrophobic core
- Bile salt & lecithin shell -lipid soluble (towards core) & water soluble parts
- Hydrophilic shell
Bile salt structure
- water soluble part
* lipid-soluble part
Excretion of cholesterol and bilirubin
• through bile secretion
What is secreted through bile?
- cholesterol
- water
- electrolytes
- bile acids
- phospholipids
- bilirubin
What is bilirubin
breakdown product of haem from RBC breakdown
Where heme breakdown occurs?
• Macrophages of the reticulo-endothelial system
how bilirubin enter liver ? through which diffusion?
- unconjugated bilirubin transported through blood to liver
- taken up via facilitated diffusion by liver
- conjugated with glucuronic acid
conjugated bilirubin actively secreted into?
bile and then intestine
In intestine, bile?
- glucuronic acid removed by bacteria.
* remaining bilirubin converted to urobilinogen
urobilinogen from intestine then?
- reabsorbed from gut into portal blood.
- some enter enterohepatic urobilinogen cycle
- remainder transported by blood to kidney.
- converted to yellow urobilin and excreted, giving urine yellow colour
Why urine yellow?
- bilirubin converted to urobilinogen in intestine
- urobilinogen transported to kidney via blood
- converted to yellow urobilin and excreted.
Urobilinogen to feces, how?
- oxidised by intestinal bacteria to
* brown stercobilin
Liver diseases
- gallstones
- cirrhosis
- hepatitis
- drug toxicity
- alcohol related
- cancer
- cholangitis
disease where bilirubin cant be metabolised properly
Gilberts disease
Gilberts disease
Inability to metabolise bilirubin properly
inherited Cu overload liver disease
Wilsons disease
Wilsons disease
Cu overload, inherited
Fe overload, inherited Liver disease
Hemochromatosis
Hemochromatosis
Fe overload, inherited
Acute liver disease - classification
- self-limiting
- leads to hepatocyte inflammation/damage
- Severe can lead to liver failure
- usually caused by drugs or viruses
Chronic liver disease - classification
- Inflammation >6months
- leads to permanent damage with structural changes = cirrhosis
- common cause = alcohol abuse
Progression of liver disease
- normal liver
- chronic injury
- inflammation/fatty liver
- early fibrosis 5-50years
- disrupt liver architecture
- Cirrhosis, portal HYP
- hepatocellular carcinoma/liver transplant
Fatty liver is ?
- reversible
* large vacuoles of triglyceride fat accumulate in liver cells via steatosis
Normal liver cell structure
- hepatocyte
- hepatic stellate cells
- sinusoidal endothelial cell
- kupfer cell
- sinusoid lumen with normal resistance to blood flow
Advanced fibrosis liver structure
- Infiltrating lymphocyte
- extracellular matrix proteins
- apoptotic hepatocyte
- activated kupfter cell
- sinusoid lumen with increased resistance to blood flow
normal vs advanced fibrosis liver - Kupffer cell
- normal =
* advanced fibrosis = activated
normal vs advanced fibrosis liver - sinusoid lumen
- normal = normal resistance to blood flow
* advanced = increased resistance
Cause - virus & routes
Hepatitis A - fecal-oral route B - body fluids, mother to baby C - body fluid D - body fluids E - contaminated food & water G - body fluids
Cause - virus & chronic/acute?
Hepatitis A - acute, generally resolves suddenly, vaccine
B - acute to chronic, cirrhosis, cancer, vaccine
C - chronic, possibly to cirrhosis, cancer, no vaccine
D - w. B, needs hepB to survive
E - self limited
G - chronic similar to HCV
Causes - drugs
- overdose paracetamol
- statins
- antibiotics eg amoxicillin, tetracycline
- methotrexate
- herbal remedies eg kava kava
- high dose vitA
- some wild mushrooms
Hepatic encelopathy and ammonia
- normally ammonia from proteins met in liver.
- detox of ammonia cant happen due to portal hypertension
- excess ammonia travel to brain.
- SE: decrease memory, confusion, decreased consciousness
Causes - alchol
- most common cause
- directly toxic to liver cells
- inflammation, lead to fatty liver, to fibrosis
- damage occurs >40g/d in men, >20g in women
- 1 unit = 9g
UK alcohol guidelines
<14 units per week
• spread over 3 days
• no alcohol in pregnancy
Cholestasis is?
- lack of bile
* due to bile duct & hepatocytes
bile duct cholestasis how?
- blocked/obstruction so no outflow
- gallstones
- carcinoma
- cholangitis
Acute Liver disease symptoms
GAJAF • generalised malaise • anorexia • Jaundice - later • asymptomatic - could be • fever
Chronic liver disease symptoms
• fatigue • weight loss • nausea/vomiting • appetite loss • cachexia • abdominal swelling • right upper ab pain, tenderness • jaundice • bleeding from gums/nose & easy bruising could be specific depending on type of disease eg gall stones
cachexia
wasting of muscle in arms & legs
Jaundice - what?
• yellowing skin & mucous membrane/sclera
Sclera
yellowing mucous membrane
jaundice - causes
- haemolysis (haemolytic jaundice)
- heptocellular damage (hepatic jaundice)
- cholestasis (obstructive jaundice)
oesophageal varices is?
- swollen veins is oesophagus
- portal HYP pushes blood into surrounding blood vessels.
- thin walled veins in oesophagus close to surface
- pressure too high = can rupture and bleed
- uncontrolled bleeding to shock to death
ascites
- high pressure inside circulation
- low pressure inside peritoneal cavity
- pressure imbalance
Ascites - causes
- portal HYP
- low plasma albumin
- salt and water retention by kidneys eg secondary hyperaldosteronism
hepatic encephalopathy
- buildup of substances/ammonia crosses BBB
* can be associated with cirrhosis, acute liver failure, portal systemic bypass of liver
hepatic encephalopathy precipitated by
- dehydrated
- hypovolaemia
- GI bleed
- CNS drugs
- alcohol
- increase diet protein
- constipation
hepatic encephalopathy - SE?
- altered mental state,
- fetor hepaticus
- asterixis
- drowsiness
- confusion
- coma
- Wernicke
Anaemia in cirrhosis
- iron homeostasis
- spleen enlarge from portal HYP
- alochol toxic to bone marrow
- reduce clotting factor synthesis
bleeding and bruising in cirrhosis
• reduce clotting factor synthesis
Splenomegaly
enlarging spleen from portal HYP
circulatory changes in liver cirrhosis
- palmar erythema
- spider naevi
- finger clubbing
skin changes in liver cirrhosis
• pruritis
Blood tests for liver disease
- LFTs
- electrolytes
- FBC
- viral screens
- blood clotting
Diagnosis of liver disease
- Blood tests
- medical history
- imaging
- liver biopsy
imagine of liver disease
- ultrasound
- CT scan
- MRI
AST
- role in gluconeogenesis - catalyses
* found in hepatocytes, other tissues
ALT
- role in gluconeogenesis
* specific to liver
ALT & AST levels in liver
- v.high in hepatitis
- high in cholestatic jaundice/cirrhosis
- AST:ALT >2 alcohol injury.
- AST:ALT<1 other liver injuries
AST:ALT
- > 2 alcohol
* <1 other liver injuries
