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imed3004 > Physiology: Liver > Flashcards

Physiology: Liver Flashcards

1
Q

What is the job of the liver?

A

Filtration/storage of blood (GIT -> liver)

Metabolism of CHO/fats/proteins/hormones/foreign chemicals/ammonia (detoxification of steroids, toxins, other hormones)

Bile formation

Storage of vitamins and Fe

Formation of blood proteins (albumin, clotting factors, and steroid binding proteins)

Immune function (kupffer cells)

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2
Q

What vitamins are stored in the liver?

A

The fat soluble vitamins and vitamin B12

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3
Q

What is unique about the liver as an organ?

A

It can regenerate to maintain functional ratio liver vs body mass.

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4
Q

What happens to hepatic circulation?

A

Blood reservoir - Blood volume ~45ml (10% of total blood volume) (CAN hold 1500ml)

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5
Q

What kind of circulation does the liver get?

A

High flow and low resistance goes to the liver (27% of CO at rest)

Hepatic artery brings the oxygen rich blood

Portal vein bring nutrient rich blood with lots of bugs from the SI. (products of digestion first pass through liver which transition slowly (~8.4 seconds)

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6
Q

What are kuppfer cells?

A

Resident macrophages that remove >99% of GIT bacteria and endotoxin via endocytosis.

Involved in iron metabolism - accumulation of ferritin.

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7
Q

How is flow controlled towards the liver?

A

Portal vein radicles -> smooth muscle

NA vasoconstriction

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8
Q

What controls flow to the liver?

A

2 things:

Sympathetic nervous system (Fight or flight response means we need less blood going to liver)

Metabolism of the liver (if more oxygen needed adenosine is produced to increase flow rate by dilating blood vessels)

No parasympathetic fibers

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9
Q

What artery is under the affect of NA vasoconstriction?

A

The hepatic artery. When it constricts it diverts blood away from the liver.

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10
Q

How is dilation of hepatic artery controlled if there is no parasympathetic control in the liver?

A

Adenosine is a product of metabolism, when oxygen is missing, arteriodilation occurs and is regulated by adenosine clearance this results in increased flow rate.

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11
Q

What other functions does adenosine have in the liver besides dilation of the hepatic artery?

A

It recruits the reserve sinusoids post meal

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12
Q

What kind of blood flow does a liver lobule use? How does this affect organisation of liver lobules in the cell?

A

Countercurrent flow between hepatic arteriole and portal venule. (oxygen is diluted from hepatic artery)

Bile producing cells are arranged from cells that are closest to the arteriole being the location of highest metabolic activity (bile production) and the furthest cells from the arteriole do the least activity.

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13
Q

Where does blood from portal vein and hepatic artery go after passing through the lobule?

A

To the central vein.

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14
Q

What kind of blood vessel is present in the sinusoids?

A

Highly fenestrated and flattened capillaries.

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15
Q

Which part of the liver lobule drains into the bile duct?

A

The space of Disse

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16
Q

Why is so much lymph produced in the liver?

A

Fenestrated capillaries don’t allow passage of albumin through which results in lots of lymph fluid production.

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17
Q

Why is the liver able to release glucose into the blood?

A

Liver has the enzyme glucose-6-phosphatase which converts G6P to Glucose.

18
Q

What happens to fructose in the liver?

A

it is converted to fructose-1-P which gets converted to glyceraldehyde and then G3P.

G3P can be converted into glucose if needed for glucose levels to be maintained or G3P can be converted into pyruvate and fatty acids for storage.

19
Q

What does liver fat metabolism result in?

A

It is the primary site of beta-oxidation

Synthesis (From CHOs/AAs and cholesterol from acetyl CoA)

Conversion (excess acetyl CoA to ketone bodies for release into plasma)

Storage

Lipoprotein formation (for transport of lipids to tissues)

Catabolises cholesterol to bile salts and secreted in bile, as well as disposal (cholesterol secreted into bile)

20
Q

What does the mevlonate pathway do?

A

Results in cholesterol being built up from acetyl CoA and from plasma LDL which is then used for other important functions.

21
Q

How are proteins metabolised?

A

Deamination (AAs -> keto acid + ammonia)

Transamination (interconversion of nonessential amino acids)

Synthesis of most plasma proteins (acute-phase proteins, albumin, hormone-binding proteins, angiotensinogen, transferrin)

Synthesis of urea (removal of ammonia from the body)

22
Q

How are amino acids used for energy?

A

They get broken down into ammonia and their carbon skeleton. Ammonia is converted into urea via the urea cycle whereas the carbon skeleton is converted into an alpha-ketoacid which then eventually forms oxaloacetate and glucose.

23
Q

How is ammonia disposed of? Why?

A

NH3 is neurotoxic and freely BBB-permeable.

Urea cycle occurs in the liver so urea is transported to the kidneys via a transporter.

Urea also diffuses into plasma which can end up in the GI tract and get converted into ammonia all over again which diffuses back into the plasma. This is the major cause of ammonia in the body.

24
Q

How does the liver detoxify the body?

A

Bugs are killed by kupffer cells..

Drugs are metabolised to yield inactive products that are either excreted in bile or converted to a form that can be disposed of in the kidneys.

Metabolizes blood-borne hormones like insulin, glucagon, etc

Abundant cytochrome P450 enzymes. (Phase 1: oxidation and hydroxylation, phase 2: esterification)

25
Q

What vitamins/minerals are stored by the liver?

A

Vitamin A

Vitamin B12

Vitamin D

Vitamin K

Iron

26
Q

How is iron stored?

A

Iron is bound to a globular protein called ferritin.

Ferroxidase: Fe2+ -> Fe3+ (safe storage)

Ferroductase: Fe3+ -> Fe2+ (soluble release)

Stores/releases iron in a controlled fashion

Liver also senses elevated plasma [Fe] and releases hepcidin which switches off ferroportin (IREG1) channels on intestine, liver and spleen reducing [Fe]

27
Q

Why is iron stored in ferric form (Fe3+)? What enzyme produces this?

A

It is very insoluble as Fe3+ . Ferroxidase produces Fe3+ from Fe2+

28
Q

How is iron stored and released?

A

Ferroxidase converts Fe2+ to Fe3+ for safe storage.

Ferroductase converts Fe3+ to Fe2+ for soluble release.

Liver also senses elevated plasma [Fe] and releases hepcidin which switches off ferroportin channels on intestine, liver and spleen to reduce [Fe]

29
Q

What is the job of hepcidin?

A

To switch off ferroportin channels on the intestine

30
Q

What is the job of bile?

A

Emulsification and absorption of fats.

Emulsification of fats in chyme.

Increases access to lipases

Facilitate uptake of digested fat products by intestinal epithelial cells.

Excretion of (hydrophobic) waste products from the blood. (Bilirubin and excess hydrophobic stuff: Cholesterol, drugs, xenobiotics, toxins)

31
Q

How are fats/HDLs taken up by the liver?

A

SR-B1

32
Q

How are fats and cholesterol taken up by the liver?

A

LDLR

LRP

33
Q

How is cholesterol added to bile?

A

Directly as it is via ABCG5/08 and exits via biliary cholesterol.

34
Q

How are bile acids exported into bile?

A

Bile acids use BSEP (Bile Salt Export Pump)

95% of bile acids are re-taken up by the ileum via ASBT (Apical Sodium dependent Bile salt transporter)

35
Q

How is bilirubin formed and released?

A

Hb is phagocytosed and split into globin+haem. This occurs in RES.

Haem oxygenase cleaves ring and releases Fe

Biliverdin reductase: reduces biliverdin to produce bilirubin

Bilirubin then binds plasma albumin (very tightly bound)

albumin bound-bilirubin enters hepatocytes via OATP, dissociates then is conjugated to glucuronic acid by glucoronyl transferase (UDP-G) on SER

Forms bilirubin di-glucunoride which is water soluble and actively pumped into canaliculus via multidrug resistant protein-2

36
Q

Why is bilirbuin diglucunorided?

A

It becomes water soluble and can be transported across membranes less readily. (prevents reabsorption at ileum)

37
Q

What happens to bilirubin?

A

Bugs convert BG to urobilinogens

Small intestinal mucosa is permeable to urobilinogen, free-bilirubin and impermeable to conjugated BG/BG2

38
Q

What causes jaundice?

A

Excessive bilirubin or BG/BG2 in the blood caused by either:

Haemolytic causes (Excessive RBC destruction/myolysis)

Hepatic causes (Impaired uptake, disturbed processing, disturbed secretion, obstruction)

39
Q

What causes jaundice of the neonate?

A

Newborn infants have poorly developed bilirubin conjugation enzymes

40
Q

What is the problematic effect of jaundice?

A

Unconjugated bilirubin in neonates in the brain causes permanent damage. (can be lethal in a condition called kernicterus)

41
Q

How can brain damage be prevented from jaundice?

A

UV light can be used to break down bilirubin.

imed3004 (50 decks)

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