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Gastrointestinal > Introduction to the Liver and Cirrhosis > Flashcards

Introduction to the Liver and Cirrhosis Flashcards

1
Q

What are the roles of the liver?

A

-Important metabolic role
-Detoxifies metabolites from the gut (all blood from gut passes through portal vein)
-Synthesis of digestive enzymes
-Production of a variety of proteins
-Storing nutrients
=80% portal vein (30% 02)
=20% hepatic artery (70% O2)

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2
Q

What does each segment of the liver have?

A

8 segments, each has:

  • Supply from portal vein
  • Hepatic artery
  • Branch of bile duct
  • Segment of hepatic vein back into IVC
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3
Q

What are hepatic lobules?

A 
Each segment
-Hepatic lobules
=Hepatic artery
=Portal vein
=Bile duct
=Drains into branch of hepatic vein
-Hexagonal shape, each corner has above
-Central vein in middle draining away
-Functions occur along sinusoids
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4
Q

Describe the hepatic sinusoid

A

-Portal triad
=Portal venous and oxygenated blood mixes
=Liver sinusoidal endothelial cells, allows passage of molecules into Space of Disse (metabolites, plasma proteins, drugs, lipoproteins)
=Hepatocytes= homeostasis
-As blood passes on, metabolic functions change (change in oxygenation)

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5
Q

What are the Liver functions?

A
  • Nutrient metabolism
  • Drug Metabolism
  • Protein synthesis
  • Secretion
  • Storage
  • Immunological function
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6
Q

Describe glucose metabolism during fasting

A

↓ insulin and ↑ glucagon → normoglycemia
-Glycogen breakdown in periportal hepatocytes
=Major glucose store in body
-Gluconeogenesis from:
=Lactate, pyruvate, amino acids and glycerol

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7
Q

Describe glucose metabolism during feeding

A

↑ insulin and ↓ glucagon → hepatic glucose uptake

-Glycogen deposition in hepatocytes

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8
Q

Describe lipid metabolism

A

-Bile digests lipids in the gut → chylomicrons → liver
-Chylomicrons metabolised by lipoprotein lipase → Cholesterol, phospholipids, triglycerides and free fatty acids
=Chylomicrons travel in lymphatics to liver

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9
Q

Describe the endogenous pathway (LDL)

A
  • VLDL synthesised by liver, fatty acids leaved off= IDL (reuptake via remnant receptor)= more fatty acids cleaved off= LDL (reuptake via LDL receptor
  • A residual fraction of LDLs bind to low affinity scavenger receptors on macrophages and are phagocytised
  • Foam cells, deposit in atherosclerotic plaques
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10
Q

Describe the Reverse Transport Pathway (HDL)

A
  • HDL synthesised by liver

- Picks up cholesterol in tissues and delivers to tissues that need it or to other lipoproteins

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11
Q

Describe the exogenous pathway (chylomicrons)

A
  • Dietary triglycerides, phospholipids and cholesterol absorbed into enterocytes of the small bowel
  • Fatty acids cleaved off
  • Reuptake via remnant receptor
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12
Q

Describe protein metabolism

A

Amino acids are absorbed from the small intestine
-Hepatocytes metabolise proteins via the Krebs or citric acid cycle
→ Hormones, neurotransmitters, plasma proteins, nucleotides (Purine and Pirimidine)

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13
Q

How is ammonia formed?

A

Absorbed from the gut (formed from bacteria so by product of digestion) but also synthesized in the liver
-Detoxified in theliverby conversion to urea by the Krebs cycle.
HEPATIC ENCEPHALOPATHY IF TOO HIGH

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14
Q

What are the 3 phases of drug metabolism?

A

-1= Oxidation, reduction and hydrolysis (new compound can have similar or different activity to parent compound; it can be converted from active to relatively inactive compound or vice versa): CYP450 enzyme in the ER
CYP1, CYP2, CYP3 and CYP3A4
-2= Conjugation in cytoplasm of hepatocytes:
→ soluble: glucuronic acid, sulphate, acetate, glycine, glutathione
=Attachment of ionised groups to drug, increases water solubility allowing excretion in bile and urine
-3= Secretion into the bile
=Excretion is mediated by ATP

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15
Q

What proteins are synthesised?

A

-Albumin
=10-12g/day and 55% of circulating protein
=enables unconjugated insoluble materials to be transported in blood
-Transport proteins
=Caeruoplasmin and Transferrin (transport of iron and copper)
-Ferritin (iron storage)
-Protease inhibitors
=ɑ1 antitrypsin
-CRP (evidence in inflammation and infection)
-AFP (screening in chronic liver disease, carcinomas secrete)
-Complement
-Coagulation factors
=Fibrinogen, II, V, VII, IX and X
=Elevated prothrombin times suggest not able to make them/ normalised doesn’t affect how probe to bleeding a patient is

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16
Q

Describe Bile secretion

A

600ml/day made up of:
-Bile acids primary (made in liver) and secondary (absorbed)
=Allow digestion of dietary fats through emulsification
-Phospholipids
-Cholesterol
-Conjugated drugs
-Electrolytes: Na+, Cl-, HCO3- and copper
-Bilirubin (also conjugated in liver)

17
Q

What is Bilirubin?

A

-Breakdown product of RBCs (Haem)
=RBCs spleen to biliverdin; to unconjugated bilirubin
-Bound to albumin for delivery to liver
-Bilirubin conjugated in liver with glucuronic acid to make soluble
=Bile secreted in small intestine; most absorbed through TI (duodenum)
=Conjugated bilirubin is not absorbed but bile is deconjugated in small bowel and colon (more hydrophobic)
=Converted to urobilinogen then some into Stercobilin (brown colour), some reabsorbed and excreted in urine as urobilin
=Colon bacteria breakdown

18
Q

What vitamins are stored in the liver?

A
  • Vitamin A, D and B12 are stored in large amounts
  • Small amounts of Vitamin K and folate are rapidly depleted with decreased dietary intake
  • Metabolises cholecalciferol vitamin D3 → activated 25-(OH) vitamin D
19
Q

What minerals are stored in the liver?

A
  • Iron stored in ferritin and haemosiderin

- Copper (affected to Wilson’s disease)

20
Q

Describe the Immunological function of the liver

A

-“firewall” filtering all blood from gut
-Kupffer cells phagocytose pathogens from gut
-Supply of important chemokines:
=Interleukins
=Tumour necrosis factor
-Priming T cell responses

21
Q

What is Liver cirrhosis?

A

Development ofregenerative nodules surrounded by fibrous bandsin response to chronic liver injury
→ portal hypertension and end stage liver disease.
4000 deaths/year due to cirrhosis
>700 transplants

22
Q

What are the causes of liver cirrhosis?

A 
-Viral infection
=Hepatitis B and C
-Alcohol
-Non Alcoholic Steato-Hepatitis
-Autoimmune disorders
=AIH
-Cholestatic liver disease
=PBC and PSC
-Metabolic causes

Fibrosis renders the liver more resistant to subsequent acute injury and that type 1 collagen, which predominates in the fibrotic scar, protects hepatocytes against various toxic stimuli

23
Q

Describe the pathology of cirrhosis

A
  • Chronic injury
  • Over time= inflammation, damage, matrix deposition, loss of parenchymal cells, angiogenesis= early fibrosis
  • Progression depends on genetics and epigenetic markers, co-factors like obesity and alcohol
  • Fibrosis reversible= remove underlying cause, anti-fibrotic drug or cell therapy
  • Disrupted architecture, loss of function, aberrant hepatocyte regeneration= cirrhosis, liver transplantation as permanent
  • Increased of hepatocellular carcinoma
24
Q

Describe hepatocyte injury

A

-Hepatocyte injury
=Apoptosis and necrosis
=Recruitment of activated macrophages
=Activation of hepatic stellate cells

25
Q

Describe the process of fibrosis

A

-Dying hepatocytes and phagocytosis
=Secretion of pro-inflammatory and pro-fibrotic mediators
=Trans-differentiation of stellate cells into activated myofibroblasts
=Matrix synthesis with collagen 1 so matrix deposition
=Reduction in matrix degradation

Removal of cause:
=Decreased production of pro-inflammatory cytokines
=Reduction of matrix metalloproteases
=Reduction in loss of myofibroblasts

26
Q

Describe Stellate cells

A

-Important in generation of fibrosis
-Activation of quiescent stellate cells/ portal or perivascular fibroblasts into myofibroblast
=Increased collagen synthesis
=Decrease production of MMP
so collagen accumulation and organ failure

27
Q

What is the sequelae of collagen deposition?

A
  • Myofibroblasts = 10x increase type 1 and 3 fibrillar collagen
  • Decrease metabolite and O2 exchange across Space of Disse= hepatocyte dysfunction
  • Increase angiogenesis, sinusoidal remodelling
  • Increase sinusoidal resistance and portal hypertension
28
Q

What are the consequences of increased sinusoidal resistance?

A

-Portal hypertension
-Systemic effects
=Portosystemic collaterals form so blood can pass from portal circulation to systemic circulation without passing through liver
–Ammonia not detoxification- BBB- encephalopathy
–Varices (extra blood vessels that form around oesophagus, stomach and duodenum= bleeding)
=Angiogenesis- increase portal venous inflow to exacerbate hypertension
-Splanchnic vasodilation= hypotension reduced in effective volume= neurohumoral activation and vasoconstriction and Angiotensin and aldosterone= sodium and water retention increases volume (ascites)= increased cardiac output

29
Q

What are the general signs of chronic liver disease?

A
  • Jaundice
  • Fever
  • Loss of body hair (hormones)
30
Q

What are the signs of compensated chronic liver disease?

A
  • Parotid enlargement
  • Spider naevi (released angiogenesis factors)
  • Xanthelasma
  • Gynaecomastia
  • Small (scarring) or large liver
  • Splenomegaly (portal hypertension)
  • Testicular atrophy (hormones)
  • Clubbing
  • Dupuytren’s contracture
31
Q

What are the signs of decompensated chronic liver disease?

A
  • Disorientation (ammonia bypass)
  • Drowsy/ coma
  • Hepatic flap
  • Fetor hepaticus
  • Ascites (portal hypertension, increased water tension)
  • Dilated veins on abdomen
  • Oedema
32
Q

How do we diagnose fibrosis/ cirrhosis?

A

-Liver biopsy
=Gold standard, quantitative
=Sampling error, morbidity
-Serum markers
=Widely available, non-invasive
=Nonspecific, gray zone for intermediate fibrosis
-Elastography
=Non-invasive, fast and user friendly, validated in chronic hepatitis
=Cost, confounding factors (body habitus) like obesity

33
Q

What are the possible results of a biopsy?

A
  • No fibrosis, Ishak stage= 0, METAVIR= F0
  • Fibrous expansion of some portal areas +/- short fibrous septa, IS= 1, F1
  • Fibrous expansion of most portal areas +/- short fibrous septa, IS 2, F2
  • Fibrous expansion of most portal areas with occasional porto-portal bridging, 3, F2
  • Fibrous expansion of portal areas with marked porto-portal bridging and porto-central, 4, F3
  • Marked bridging P-P and P-C with occasional nodule, 5, F3
  • Nodular cirrhosis, 6, F4
34
Q

What are the serum markers?

A

-Albumin
=Decreases in end-stage liver disease due to decreased synthesis
=T1/2: 20 days therefore useful in cirrhosis
-Prothrombin time
=Decreased synthesis of clotting factors (I, II, V, VII, X) →↑ PT
=In cirrhosis associated with more advanced disease
-Bilirubin
=Increased in end stage cirrhosis due to decreased clearance
-Platelets
=Decreased in cirrhosis
=Splenomegaly (portal hypertension) →↑ consumption
=Decreased Thrombopoietin production by cirrhotic liver

35
Q

What is the purpose of composite scores?

A
  • Used to assess risk of patients of having advanced cirrhosis
  • Triaging
  • Screening tests
36
Q

What is Fibroscan?

A
  • Liver should be like jelly, elastic
  • More fibrosis= less elastic= more solid= probe measure through vibrations
  • Liver stiffness
  • METAVIR scores
  • Varies depending on type of aetiology
  • Non invasive measure
37
Q

What is the Child-Pugh Score?

A

Assess risk and mortality

  • Bilirubin, serum albumin, INR, Ascites, Hepatic encephalopathy
  • Class A, B, C with different survival rates

Gastrointestinal (48 decks)

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