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Alimentary system > The Liver > Flashcards

The Liver Flashcards

1
Q

Why do we need to know about the liver

A

Liver disease affects 2 million people in the UK and the incidence is increasing

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2
Q

Describe the statistics associated with liver disease

A

Accounts for >1million hospital admissions each year
11,575 people died from liver disease in 2009 (9,231 in 2001)
~ 1 in 50 all deaths
1 in 10 deaths of people in their 40’s are due to liver disease
70% die in hospital

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3
Q

Where is the Liver found

A

Most of the liver is found in the URQ, some in the ULQ
Protected by the abdominal tissue and thoracic wall
Sits nicely in the diaphragm

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4
Q

Anteriorly, how many lobes does the liver have

A

The liver can be split into two lobes (right and left), which are separated by the falciform ligament.
Right lobe is larger
Gall bladder sits in right lobe

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5
Q

What is the falciform ligament also known as

A

Ligamentum teres
Joins form coronary ligament (right lobe)
and left triangular ligament (left lobe)

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6
Q

What is the role of the ligaments

A

Attach the liver to parts of the body

Falciform ligament attaches the liver to the diaphragm

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7
Q

Posteriorly, what other lobes are seen

A

Quadrate lobe- below hilus

Caudate lobe- between hilus and left hepatic vein

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8
Q

What is found in the hilus of the liver

A

Hepatic portal vein
Hepatic artery proper
Common bile duct
Gall bladder

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9
Q

Describe a Lap cholecyetectomy

A

Lap cholecyetectomy: gallbladder in junction of segments 4 and 5

Calot’s triangle bound by the cystic duct, bile duct and cytic artery. It is this triangular space which is dissected in a cholectystcomy to identify a window to safely expose the gallbladder

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10
Q

Describe Couinaud classification of the Liver

A

8 functionally independent segments
Centrally: portal vein, hepatic artery and bile duct
Peripherally: hepatic vein

Each segment can be resected without damaging those remaining as they all have their own blood supply and venous drainage

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11
Q

Describe the location of the lobes

A

Caudate lobe
Lateral to falciform ligament and superior to portal venous supply
Lateral to falciform ligament and inferior to portal venous supply
Medial to falciform ligament
Medial and inferior right hemisphere
Posterior portion of right hemisphere
Above 6
Above 5 (medial and superior right hemisphere)

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12
Q

Describe the venous drainage of the lobes

A

Each subsection drains into its own vein, with those subsequently draining into the left, middle and right hepatic veins before joining the vena cava

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13
Q

Describe the blood supply to the liver

A

Rich blood supply- 25% of resting cardiac output

Dual blood supply:
20% arterial blood from the hepatic artery (left and right branches)
80% venous blood draining from the gut through the hepatic portal vein (HPV)

Blood from the liver drains into the inferior vena cava via the hepatic vein

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14
Q

What does the dual blood supply to the liver reflect

A

The liver receives a dual blood supply, which reflects its important metabolic, secretary and immunological functions. The main perfusing vessels are the hepatic artery (blood from heart) and hepatic portal vein (blood from the gut).

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15
Q

Describe hepatic lobules

A

Structural unit of liver that is roughly hexagonal in shape
Each corner consists of a portal triad that links with 3 adjacent lobules
At the centre of each lobule is a central vein which collects blood from the hepatic sinusoids to return it to the systemic venous system via the hepatic veins]
Within the lobule, there are rows of hepatocytes, with each hepatocyte having a sinusoid-facing side and a bile-canaliculi- facing side

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16
Q

What does the portal triad consist of

A 
Portal tracts are composed of:
an arteriole
a branch of the portal vein
a bile duct
with blood flowing inwards and bile flowing outwards
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17
Q

Describe the role of the hepatic portal vein

A

This blood vessel is carrying mixed venous blood directly from the G.I organs and spleen
Therefore, it is rich in raw nutrients, bacteria, toxins and waste products (from the spleen)
The hepatocytes can process nutrients, detoxify the blood and excrete waste before the blood returns to the systemic circulation

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18
Q

Describe the role of the hepatic artery

A

brings some oxygen-rich blood to liver tissue to support high energy demand of hepatocytes (fuses with portal vein to form sinusoids)

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19
Q

Describe the role of the bile duct

A

bile produced by hepatocytes drains into tiny canals (bile canaliculi) which coalesce with cholangiocyte-lined bile ducts located around lobules

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20
Q

What is key to remember about blood supply to the liver

A

It is mixed- and so is poorly oxygenated

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21
Q

What does the liver have roles in

A

Digestion, biosynthesis, energy metabolism, storage, degradation and detoxification

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22
Q

List the cell types found in the liver

A 
Hepatocytes
c.80%
Endothelial cells
Lining blood vessels and sinusoids
Cholangiocytes (aka bile duct epithelial cells)
Lining biliary structures
Kupffer cells
Fixed phagocytes (liver macrophages)
Hepatic stellate cells
Vitamin A storage cells (Ito cells), may be activated to a fibrogenic myofibroblastic phenotype
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23
Q

Describe the endothelial cells in the Liver

A

have no basement membrane, with many fenestrations and a discontinuous endothelium to become very leaky to allow transfer of lipids/proteins/carbs
Found between hepatocytes and space of disse and lining the hepatic sinusoids

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24
Q

Describe the kuppfer cells

A

sinusoidal macrophages that are stellate shaped and attached to endothelial cells to eliminate and detoxify substances arriving into liver from portal circulation
15% of liver population
Attach to endothelial cells lining the hepatic sinusoids

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25
Q

Describe the stellate cells

A

exist in quiescent state to store VItA in liver cytosolic droplets, becoming activated in response to liver damage; proliferate and deposit collagen in the extracellular matrix
they are chemotactic too
perisinusoidal (attach to endothelial cells in space of disse)

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26
Q

Describe hepatocytes

A

approx. 80% liver mass, cuboid cells that synthesise albumin, clotting products and bile salts while receiving nutrients and metabolising drugs

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27
Q

Describe cholangiocytes

A

secrete bicarbonates and water to form bile

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28
Q

What is meant by the space of disse

A

region of free space between capillaries and hepatocytes

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29
Q

How are hepatocytes arranged in the liver

A

Cords (sheets) of hepatocytes

Radiating from a central vein.

80% of the liver mass.

30
Q

What is meant by the hepatic acinus

A

functional unit of liver tissue that is harder to define; consists of two adjacent sixths of a lobule that share two portal triads and extend as far into the lobule as the central veins

31
Q

Describe the inter lobule structure

A

One portal triad sits at the junction between 3 lobules

32
Q

Summarise the different zones of the acinus

A

The terminal acinus is centred on the the portal tract and each hepatic acinus is centred on the line connecting two portal triads

It is the elliptical shaped appearance of the histological appearance and is demarcated by zone:

  1. Periportal
  2. Transition zone
  3. Pericentral

Unit of hepatocytes divided into zones dependent on proximity to arterial blood supply

33
Q

Describe the relations of the bile canaliculus

A

Canaliculus interface between sinusoids (sinusoidal faces) and hepatocytes (lateral faces)

34
Q

Describe the 3 zone model of the acinus

A

blood received from vessels at A and drains to B, so those in zone one receive early exposure to toxins, but also most oxygen; Zone 1 = high toxin risk but also high oxygen supply; Zone 2 = medium toxin risk and medium oxygen supply; Zone 3 = low toxin risk but also low oxygen supply
Portal triad is at A

35
Q

Describe the histology of the endothelial cells

A

nuclei red and flat

36
Q

Describe the histology of the kupffer cells

A

cytoplasm blue

nuclei red

37
Q

Describe the histology of hepatocytes

A

nuclei red and round

38
Q

What does the activation of hepatic stellate cells lead to

A

Vitamin A storage
Activation = ECM production (fibrogenesis)
has a role in liver cirrhosis
activated by pro-inflammatory environments

39
Q

What are the other roles of Kupffer cells

A

Phagocytosis (inc. RBC breakdown)
Secretion of cytokines that promote HSC Activation - proliferation, contraction and fibrogenesis
remove bilirubin from RBCs
important physiologically but can be pathological

40
Q

Summarise the metabolism of carbohydrates

A

Important to control blood glucose (endocrine course)
After a meal, blood glucose  and is taken up by tissues
Stored as glycogen mainly in muscle and liver
Breakdown liver glycogen maintains blood glucose concentration between meals (muscle cannot release glucose back into blood)
24h fast will exhaust liver glycogen (80g

41
Q

Describe gluconeogenesis

A

Muscles: glucose enters muscles and is used for glycolysis to produce pyruvate; either used to produce Acetyl CoA for TCA or undergoes fermentation to lactate
Hepatocytes: lactate travels to liver and is converted to pyruvate using lactate dehydrogenase; 6 ATP are invested in gluconeogenesis to produce glucose

42
Q

When can gluconeogenesis take place

A

During muscle contractions, ATP is constantly being used to supply energy and more ATP is produced to replenish supplies. If muscular activity continues, the availability of oxygen for use at the end of the electron transport chain becomes the limiting factor and the cells soon exhaust their supplies of oxygen. When this happens, the citric acid cycle is inhibited and causes pyruvic acid to accumulate.
However, glycolysis continues even under anaerobic conditions even though the citric acid cycle works only under aerobic conditions.

43
Q

What is meant by hitting the wall

A

loss of glycogen stores

44
Q

Describe protein metabolism

A

Metabolism of proteins: important to produce plasma proteins
Muscles: in fasted state, break down amino acids
Hepatocytes: use amino acids to produce proteins such as plasma proteins, clotting factors and lipoproteins; also perform transamination reactions to produce amino acids not found in diet e.g. Alanine and alpha-ketoglutarate converted to pyruvate and glutamate and deaminations

45
Q

Describe the synthesis of non-essential amino acids

A

Synthesis of dietary “non-essential” amino acids. Start with appropriate -keto acid precursor (carboxylic acid and ketone group). Exchange of an amine group from an amino acid to a keto-acid. In this example, alanine enters the liver and can react with the keto acid (alpha keto glutarate) to produce the amino acid glutamate and the ketoacid pyruvate (requires the relevant transaminase enzyme plus cofactor). This reaction is reversible in the presence of a different transaminase that could then convert glutamate and pyruvate back to alanine and alpha keto glutarate.

46
Q

Describe transamination

A

Different keto-acids can be converted to multiple amino acids depending on the transaminase enzyme (vital for production of non-essential amino acids.

different keto acids as amine acceptors and different transaminases to produce different amino acids

47
Q

List some transaminase reactions

A

AlphaKG: glutamate, proline and arginine
Pyruvate: alanine, valine and leucine
Oxaloacetate: aspartate, methionine and lysine

48
Q

List some non-essential amino acids

A

Glutamate
proline
Alanine
aspartate

49
Q

What is the issue for muscles in terms of respiring amino acids

A

Muscle can potentially utilise amino acids to produce glucose for energy;
BUT
To convert pyruvate to glucose requires energy
To remove nitrogen as urea requires energy

Solution – transfer problem to the liver (glucose-alanine cycle)

50
Q

Describe the process of deamination

A

occurs using the glucose-alanine cycle; alanine transferred to liver and reacts with alphaKG to form glutamate and pyruvate; glutamate then converted to urea using 4ATP and pyruvate converted to glucose using 6ATP

Alanine is made from pyruvate (glycolysis) and glutamate (a,a breakdown) in muscle cells

Urea is excreted into the blood- to go to the kidney for removal

51
Q

What is the importance of urea

A

Glutamate metabolism actually produces NH3 which is very toxic to the body (especially brain), so liver converts it to water soluble urea.

52
Q

Describe some important amino acids

A

Four of the amino acids: glutamate, aspartate, alanine and glutamine are present in cells at much higher concentrations than the other 16. All four have major metabolic functions in addition to their roles in proteins, but glutamate occupies the prime position. Glutamate is special because it is chemically related to 2-oxoglutarate (= alpha keto glutatarate) which is a key intermediate in the citric acid (Krebs) cycle. Glutamate can be reversibly converted into oxoglutarate by transaminases or by glutamate dehydrogenase. In addition, glutamate can be reversibly converted into glutamine, an important nitrogen carrier, and the most common free amino acid in human blood plasma. Alanine is the principal amino acid released from muscle tissue during starvation. It is an important substrate for hepatic gluconeogenesis, and alanine transamination is required for the proper maintenance of fasting blood glucose concentrations.

53
Q

What is the main energy store in the body

A

Fat main energy store in body - 100x glycogen. Stored in adipose and liver. When glycogen stores full, liver can convert excess glucose and amino acids to fat for storage

54
Q

Describe triglyceride metabolism

A

Adipose tissues: convert triglycerides to NEFAs
Hepatocytes: NEFAs converted into acetyl coA (beta oxidation)
Used in TCA cycle or to make ketone bodies for tissue energy source
ketones are mobile acetyl-coA

55
Q

What can glucose be converted into once it enters the hepatocyte

A

Glucose entering the liver can be converted to several components of lipoproteins – glycerol, fatty acids and cholesterol. Glucose can be directly converted to glycerol or via the TCA cycle and be converted to acetyl CoA via pyruvate (within the mitochondria). Acetyl CoA can be converted to cholesterol (via HMG CoA reductase) or can also be converted to fatty acids (via the intermediate malonyl CoA).

56
Q

Describe lipoprotein synthesis

A

lycerol is converted to triglycerides and when combined with fatty acids, cholesterol, apoproteins and phospholipids, lipoproteins are formed (usually HDLs and VLDLs are produced where HDLs are empty and pick up excess cholesterol and VLDLs transport fatty acids to tissues)

57
Q

Describe the different types of lipoproteins

A

The liver produces two lipoproteins. VLDL and HDL. VLDL has a high triacylglycerol component and it’s major role is to deliver fatty acids to body tissues (lipoprotein lipase cleaves the fatty acids from triglycerides). Those fatty acids can be used as an energy source of can be stored in the adipose tissue as tri-glycerides. HDL are often referred to as ‘empty’ lipoproteins – they have high protein content but low fat content. Their role is to mop up excess cholesterol in the circulation and return to the liver – hence why they are often referred to as ‘good’ fat. Once VLDL have delivered fatty acids to tissues, they are converted to LDL which are very high in cholesterol. The LDL deliver cholesterol to tissues which then use the cholesterol to make hormones and to maintain cell membrane integrity. Any excess cholesterol is returned to the liver and excreted in bile.

58
Q

Describe the storage roles of hepatocytes

A

Storage of fat soluble vitamins (A,D,E,K). Stores sufficient 6-12 month except Vit K where store is small. Vit K essential blood clotting

Storage of iron as ferritin. Available for erythropoiesis
Also store copper

59
Q

Describe the roles of hepatocytes in detoxification

A

P450 enzymes make compounds more hydrophilic and then phase 2 enzymes attach water soluble side chains to make them less reactiv

60
Q

Describe the ultrastructure of hepatocytes

A

Peroxisomes: key role in detoxification, waste management and cholesterol/bile synthesis
Cytoplasmic enzymes: support deamination/glycogenolysis
Smooth ER: essential for carb/phospholipid synthesis
Mitochondria: produces ATP to meet high demand
Rough ER: abundant for protein synthesis e.g. Clotting factors/albumin
Golgi Apparatus: package many manufactured molecules for exocytosis
Lysosomes: acidic organelle needed for breakdown of lipids/proteins/carbs and nucleic acids
Glycogen: stored glucose polymer

61
Q

Describe the biliary tree

A

The biliary tree describes the anatomical structures responsible for the transit and storage of bile. Technically, the biliary tree starts in millions of bile canaliculi adjacent to the hepatocytes (bile producing cells). These canaliculi then drain into small ductules, which in turn drain into small bile ducts. Small bile ducts coalesce into larger bile ducts for each liver segment (e.g. 2, 4a). These merge together to form the right and left hepatic ducts, which converge to form the common hepatic duct. Connected to this duct is the cystic duct, which connects the gall bladder (a small muscular storage organ) to the biliary tree. The merging of the common hepatic duct and the cystic duct forms the common bile duct, which extends towards the duodenum. At its distal end the pancreatic duct joins and the vessel is then called the ampulla of Vater, which opens up into the medial wall of the duodenum at the duodenal papilla.

62
Q

What are the functions of bile

A

Functions of bile:
Cholesterol homeostasis: secretion/excretion to fine tune serum concentration
Absorption/digestion: bile salts solubilise fats and VitA/D/E/K (lipid-soluble vitamins)
Toxin excretion: endogenous/exogenous

63
Q

What is in bile

A

cholesterol
bile salts
bilirubin and drug metabolites (for excretion in faeces)
bile is an aqueous solution- so lots of water and other solutes

64
Q

What are bile acids/salts

A

Primary bile acids secreted in liver:
Cholic acid
chenodeoxycholic acid

converted to deoxycholic and lithocholic acids respectively by gut bacteria; aq solution so also contains water and solutes, and is yellow/green due to biliverdin/bilirubin

65
Q

Describe the production of bile

A

500ml day-1 with 60% from hepatocytes (reflect serum concentrations; secrete bile acids, lipids and organic ions) and 40% from cholangiocytes (alter pH, allow water to enter bile, reabsorb sugars/acids and secrete HCO3- and Cl-, IgA exocytosed

66
Q

What does bile do

A

reduces surface tension of fats

helps form micelles

67
Q

When is bile released

A

constantly being synthesised and stored in gall bladder

CCK stimulates gall bladder for a big dose

68
Q

What does the gall bladder do

A

stores 50ml bile, acidifies by absorbing HCO3-, and concentrates by reabsorbing ions to create an osmotic gradient- removing around 80-90%of its volume

69
Q

Describe the enteropathic circulation

A

cycling of substances between gut and liver by continuous reabsorption in the gut and hepatocyte secretion; allows for recycling of bile salts to be more efficient; some drugs are secreted to bile and faeces but enterohepatic circulation may lead to reabsorption and re-entering the portal circulation cyclically to increase their half-life

70
Q

Describe how the liver may process some drugs

A

One way the liver processes some drugs is to excrete them via bile (to avoid them going into circulation), and eventually the faeces. However they may get reabsorbed in the small intestine and re-enter the portal circulation cyclically, significantly increasing their half-life.

Alimentary system (15 decks)

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