wk 2 GI and Liver - part 1 Flashcards

1
Q

liver segments

A
  • 8
  • Each has own supply from portal vein and hepatic artery
  • Each has branch of bile duct draining it
  • Each has segment of hepatic vein draining back into IVC
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2
Q

liver microanatomy

A
  • Hepatic globules each with own supply of hepatic artery, portal vein and bile duct
  • Draining into branch of hepatic vein
  • Hexagonal shaped segments
  • Central vein draining away in the middle
  • In between portal triads in Sinusoids are where functions of liver performed
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3
Q

hepatic sinusoid

A
  • Portal triad at one side
  • Portal venous blood and oxygenated blood mix and travel along sinusoid towards central vein
  • Sinusoid lined by liver sinusoidal endothelial cells
    o These maintain blood cells in sinusoid
    o Allow passage of metabolites, plasma proteins, lipid proteins, viruses etc into space of Diss
    o Hepatocytes then maintain homeostasis, sustaining nutrients, secrete bile and detoxify drugs in space of Disse
    o As blood passes along sinusoid metabolic functions of hepatocytes change (in part due to change in oxygenation as you move down this gradient
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4
Q

liver functions

A
  • Nutrient metabolism
  • Drug Metabolism
  • Protein synthesis
  • Secretion
  • Storage
  • Immunological function
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5
Q

glucose metabolism during fasting

A
  • Dec. insulin and inc. glucagon leading to normoglycaemia

o Glycogen breakdown in periportal hepatocytes
 Major glucose store in body

o Gluconeogenesis from
 Lactate, pyruvate, amino acids, glycerol

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6
Q

glucose metabolism during feeding

A
  • Inc. insulin and dec. glucagon leading to hepatic glucose uptake
    o Glycogen deposition in hepatocytes
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7
Q

lipid metabolism

A
  • Bile digests lipids in the gut -> Chylomicrons -> liver

- Chylomicrons metabolised by lipoprotein lipase -> cholesterol, phospholipids, triglycerides and free fatty

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8
Q

protein metabolism

A
  • Amino acid is absorbed from the small intestine
    o Hepatocytes metabolise proteins via the Krebs or citric acid cycle
    o -> hormones, neurotransmitters, plasma proteins, nucleotides (purine and pyrimidine)
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9
Q

ammonia

A
  • Absorbed from the gut but also synthesised in the liver
    o Detoxified in the liver by conversion to urea by the Krebs cycle
    o By product of digestion
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10
Q

albumin

A
  • Albumin
  • 10-12g/day and 55% of circulating protein
  • Transport proteins
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11
Q

bile

A

600ml/day made up of
o Bile acids primary (made in liver) and secondary (absorbed)

Allow digestion of dietary fats through emulsification

whats in bile?
BILE ACIDS
o Phospholipids
o Cholesterol
o Conjugated drugs
o Electrolytes – Na+, Cl-, HCO3- and copper
o Bilirubin
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12
Q

bilirubin

A
  • Heme is breakdown product of red blood cells
  • In spleen heme broken down to biliverdin -> unconjugated bilirubin
  • Transported down by albumin to liver where its conjugated and made soluble
  • Then excreted in bile going into deudenum
  • Conjugated bilirubin converted to urobilinogen

o Some converted into stercobilin -> gives stools brown colour
o some reabsorbed
o Some absorbed into blood and is excreted in urine
 Kidneys convert from urobilinogen to urobilin
 And excreted in the urine (giving yellow hue)

  • When you get bile duct obstruction you get pale stools this is due to the fact bilirubin is needed to give stools brown colour
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13
Q

vitamin storage

A
  • A,D and B12 are stored in large amounts
  • Small amounts of vit K and folate are rapidly depleted with decreased liver function
  • Metabolises cholecalciferol vitamin D3 -> activated 25-(OH) vitamin D
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14
Q

mineral storage

A
  • Iron stored in ferritin and haemosiderin

- Copper (can be affected by Wilson’s disease = excess levels of copper)

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15
Q

immune functions of the liver

A
  • ‘firewall” filtering all blood from gut
  • Kupffer cells phagocytose pathogens from gut
  • Supply of important chemokines
    o Interleukins
    o Tumour necrosis factor
  • Priming t cell repsonses
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16
Q

definition of liver cirrhosis

A
  • Development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury
  • > portal hypertension and end stage liver disease
  • 4000 deaths/ year due to cirrhosis
  • > 700 transplants
  • Increase in mortality overtime
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17
Q

causes of cirrhosis

A
- Viral infection 
o	Hep N and C
- Alcohol
- Non-alcohol steato-hepatitis
- Autoimmune disorders
o	AIH
- Cholestatic liver disease
o	PBC and PSC
- Metabolic causes
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18
Q

pathology of cirrhosis

A
  • Chronic injury
  • Overtime damage
  • Loss of pancrine cells and angiogenesis
  • Depends on genetics, alcohol, obesity
  • Fibrosis in reversible as you can remove the underlying cause

o However, if underlying cause cont. u get loss of architecture, loss of function, no hepatocyte regeneration -> cirrhosis
o Outcome is liver transplantation
o Once you have cirrhosis once you remove the underlying cause it doesn’t heal
o Once have cirrhosis at risk of hepatocellular carcinoma

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19
Q

hepatocyte injury results in…

A
  • Apoptosis and necrosis of hepatocytes
  • Recruitment of macrophages
  • Activation of macrophages and hepatic stellate cells
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20
Q

fibrosis

A
  • Inflammatory response leads to secretion of pro-inflammatory and pro-fibrotic mediators
  • Trans differentiation of stellate cells into myofibroblasts
  • These lead to matrix synthesis with a-SMA and collagen 1 – matrix deposition
  • Reduction in matrix degradation
  • If remove cause of injury you get dec. prod. Of pro-inflammatory cytokines
    o Leads to matrix degradation loss of myofibroblasts too
    o Progression of fibrosis
21
Q

stellate cells

A
  • Important in gen of fibrosis and cirrhosis
  • Activation of stellate cell + portal/ perivascular fibroblasts = myofibroblast
  • Myofibroblasts lead to inc. collagen synthesis + dec. in matrix metalloproteases
  • Collagen accumulation and organ failure
22
Q

consequence of inc. sinusoidal resistance

A

-Portal hypertension
o Portosystemic collaterals
 Meaning blood can pass from portosystemic to systemic system without going through the liver

• Eg ammonia doesn’t get de-toxified by liver can go to BBB causing cephalopathy

23
Q

varices

A

 Extra blood vessels around oesophagus and stomach and spleen
 Can lead to bleeding

  • caused by portal hypertension as blood can’t flow through normal route and so creates an alternative
  • bad because blood isn’t filtered by liver
24
Q

angiogenesis

A

 Inc portosystemic collaterals

 Inc. Porto venous blood inflow more hypertension

25
splanchnic vasodilation
```  hypotension  relative decreased in effective volume  vasoconstriction  activation. Of reno-angiotensin aldosterone system • surge in water retention • increase fluid vol. • ascites • increased CO • increased venous blood flow – inc. portohypertension ```
26
physical signs of chronic liver disease
Liver in cirrhosis can be small or large - In advanced - small due to high level of scarring Splenomegaly - Due to portal hypertension - Feeds back through splenic vein leading to hypertrophy of spleen Loss of body hair - Due to effects on hormones Spider Naevi - Due to angiogenic factors released Neurological effects - Due to ammonia bypass in liver Ascites - Due to portal hypertension - Fluid retention
27
how to diagnose fibrosis/ cirrhosis
Liver biopsy - Gold standard, quantative - Sampling error (may underscore if chose wrong place), morbidity Serum markers - Widely available, non-invasive - Nonspecific, grey zone for intermediate fibrosis - Can tell if someone cirrhotic but hard to tell if fibrotic Elastography - Non-invasive, fast and user-friendly, validated in chronic hepatitis - Cost, confounding factors - Hard to get reading in obese patients
28
serum markers in liver cirrhosis
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) -> inc. PT - In cirrhosis associated with more advanced disease BILIRUBIN - Increased in end stage cirrhosis due to decreased clearance PLATELETS - Decreased in cirrhosis - Splenomegaly -> inc. consumption - Decreased thrombopoietin produced by cirrhotic liver
29
fibroscans
- Works because liver should be like jelly/elastic - As more fibrotic liver becomes more solid - Probe measures the stiffness of liver by sending impulses through liver - Diff. scores suggest different types of liver cirrhosis and idea of extent of fibrosis
30
child-pugh score
- Assess risk of mortality after deciding patients cirrhotic
31
jaundice
- Yellowish pigmentation of the skin, membranes and sclera (conjunctival membrane) - Jaundice (jaune) = yellow - Visible at bilirubin level >35umol/L
32
types of jaundice
- Pre-hepatic (before liver) - Hepatic (in liver) - Post hepatic (consequence of something outside the liver)
33
pre-hepatic jaundice
- Eg Haemolysis - More bilirubin into system at very beginning - Too much unconjugated bilirubin for liver to conjugate it all - As water insoluble, does not enter urine
34
hepatic jaundice
- Mixed type of jaundice as… - Liver can’t uptake unconjugated bilirubin and can’t conjugate bilirubin normally ``` Caused by… Hepatocyte damage due to… - Cirrhosis - Viruses – hepatitis, CMV - Drugs – paracetamol - Alcohol - Sepsis - Right heart failure ```
35
post-hepatic jaundice
- Blockage type cause after liver - Bilirubin still conjugated and so water soluble - Some water-soluble bilirubin leaks out into blood stream and is excreted by kidney - Makes urine really dark - Bilirubin not getting in poo – poo really pale - ITCHY – due to bile salts not getting through normally and therefore in skin ``` Caused by… Classifications -> - Within the lumen eg gallstones - Within the wall eg tumours - External compression eg pancreas cancer (squishing bile duct) ```
36
obstructive jaundice - malignancy
- hilar cholangiocarcinoma - hilar lymphadenopathy - distal cholangiocarcinoma - ampullary tumours - pancreatic tumours
37
whipples
- Operation for obstructive cancers at bottom - Distal cholangiocarcinoma’s - Ampullary tumours - Pancreatic tumours Take out… - Gallbladder - Distal bile duct - Duodenum - Stomach - Pulling up jugular lens and stitching it back together
38
ERCP - endoscopic retrograde cholangiopancreatography
- A camera you swallow down - Goes through the stomach into duodenum - End of it looks straight at ampulla - Put down wires into bottom of bile duct - Take samples of cancer for lab - Put in stents that go through the cancer and give pathway for bile to drain - This helps with symptoms they get from jaundice - Can also do this for benign disease - Eg gallstones
39
features of obstructive jaundice
PALE STOOLS, DARK URINE, ITCH
40
obstructive jaundice on examination
- Peripheral stigmata of liver disease... - Finger clubbing - palmar erythema (red palms) - dupuytren’s contracture (palmar thickens, fingers bending over) - sclera for jaundice - virchow’s node (lump in neck – sign of cancer) - spider naevi (capillaries in skin – press them disappear and come back when release) - gynecomastia - hepatomegaly - splenomegaly (portal hypertension) - ascites - palpable gall bladder
41
investigation for obstructive jaundice
haematology - FBC, if anaemic consider cancer - Abnormal clotting in liver disease - LFTs – raised bilirubin Looking at patterns of liver test (not definitive) - If ALP> ALT/AST = obstructive picture - ALT/AST >ALP, liver disease Liver screening Ultrasound – gallstone, CBD dilatation, liver/ pancreas mass - If blockage look for ducts in liver (if they’re blown up its post-hepatic due to high pressure) CT abdomen with contrast, MRI/BRCP - Good for showing cancers - MRI is best test for seeing there’s stones in bile duct itself Tissue biopsy if above unclear
42
management of jaundice
Depends on underlying condition - Treat symptoms - Analgesia - IVI - Antibiotics if septic - Vit K and chlorphenamine Treat underlying cause - Pre-hepatic -> stop haemolytic process - Hepatic -> anti-virals, prevent deterioration of cirrhosis eg alcohol, drugs - Obstructive – ERCP/stenting, surgery, palliative care
43
gall stones basic anatomy
- Gall bladder drains by cystic duct into common bile duct down the way - Drains upwards after cystic duct joins drains via common hepatic duct - Divides into left and right branches - Right into anterior and posterior - Common hepatic artery comes from the coeliac trunk - Cystic artery (artery to the gall bladder) comes from right hepatic artery - Head of pancreas down low at head of pancreas and the ampulla - Ligament between the liver and the duodenum - Bile duct - Hepatic artery - Portal vein
44
incidence of gallstones
- 10 to 20% of adults - 80% asymptomatic - Females 2:1 ratio to males - Fair, fat, fertile, forty
45
types of gallstones
mixed gallstones -> most common pure cholesterol gall stones haemolysis/ haemolytic anaemia -> made of unconjugated bilirubin
46
clinical presentation of gall stones
- Right upper quadrant pain or epigastric pain - Colicky (get better then worse) or constant - Dyspepsia, nausea, vomiting - Can be mistaken for acid reflux
47
gall stones symptoms
Biliary colic - Most common - Pain gets worse then better - Stones are floating around – sometimes balls get trapped = pain Acute cholecystitis - Inflammation and sometimes infection - Pain starts as colicky but becomes more constant - Temperature due to inflammation - Treat with antibiotics - Sometimes emergency operation Obstructive jaundice - If galls tones get out of gall bladder - Into the bile duct - Causing jaundice - ERCP – try to drag stone out into duodenum Acute pancreatitis - Gall stone falls out of gall bladder - Causes pressure change in pancreatic duct as it goes down - Irritation and inflammation of the pancreas
48
management of gall stones
- Analgesia - Antibiotics - percutaneous drainage - ERCP - Surgery
49
alcohol unit
1 unit = 10ml or 8g of pure alcohol 1 unit processed in one hour ABV = % alcohol of total liquid volume Units = ABV% x volume (in litres) (of drink consumed