-
List important functions of the liver
- a.
- Liver produces bile from bile acids and salts,
- cholesterol and biliruben pigment removed from the blood
- b.
- Bile stored in gallbladder
- c.
- Reabsorbs bile returned to live via portal vein
- d.
- Synthesize proteins- transport molecules mostly
- (albumin, transferrin, ceruloplasmin)
- e.
- Syn glycogen- storage of glucose
- f.
- Syn lipids and lipoproteins- repackaging
- g.
- Syn Clotting factors- protein based
- h.
- Syn urea- N waste from the deamination of
- proteins
- i.
- Storage of fat soluble vitamins (A,D,E,K, B12
- j.
- Key role in transport/storage/metabolism of
- metals like iron
- k.
- Converts many noxious or insoluble chemicals
- into other forms that are less toxic and more water soluble an therefore
- excretable by the kidneys
-
Bile
- a.
- Function- facilitates digestion and absorption
- of lipids in small intestine
- b.
- Produced from bile acids and salts, cholesterol
- and biliruben pigment removed from the blood
- c.
- Stored in gallbladder where it is concentrated
- up to 10x
- i. After
- meal, gallbladder contracts and expels bile into intestine
- ii. Bile
- digests and facilitates lipid absorption
- iii. Eventually
- returned to liver via the portal vein
-
Vitamins stored in the liver
-
Detoxification role of liver
- a.
- Converts noxious or insoluble compounds into
- other forms that are less toxic and more water soluble and therefore excretable
- by the kidneys
-
Formation of biliruben
- a.
- Formed from the breakdown of hemoglobin when
- aged RBCs are removed from circulation
- b.
- Protein (globin) is reused
- c.
- Iron enters iron stores and is reused
- d.
- Porphyrin is broken down as a waste product and
- is excreted
- i. Action
- of splitting the porphyrin ring and releasing the iron and globin forms
- biliruben
- ii. Biliruben
- is transported to the liver bound to albumin and is taken up into the hepatic
- cells
- iii. Conjugated
- by an enzyme within the hepatocyte
- iv. Conjugated
- bili passed along with other bile constituents to the gallbladder and
- eventually the GI tract
- v. Acted
- upon by bacterial enzyme in GI tract producing urobilinogen
- vi. Urobilinogen
- is oxidized further to urobilin and excreted in the stool (pigment)
-
Biliruben terminology
- a.
- Unconjugated biliruben (indirect)- form by
- splitting of the porphyrin ring, and release of iron and globin. Transported by
- albumin
- i. Before
- acted upon by enz in hepatocyte
- b.
- Conjugated biliruben (direct)- after acted upon
- by enz in hepatocyte
-
Jaundice
- b.
- Yellowish discoloration of the skin, fingernail
- beds, and sclera due to the accumulation of bilirubin
- i. Caused/associated
- with jaundice
- ii. Damage
- to the brain of infants due to the build up of unconjugated bili
-
Pre-hepatic hyperbilirubinemia causes
- a.
- Caused by the increased hemolysis and increased
- degradation of hemoglobin
- b.
- Increase in unconjugated(indirect) bili (not
- water soluble)
- c.
- Liver is functioning normally but is unable to
- keep up with demand for conjugation
- d.
- Happens in certain anemias
- e.
- Normal enz with exception of LD & AST due to
- their high concentrations in RBCs
- f.
- Very high LD concentrations are observed with
- intravascular hemolysis
-
Hepatic hyperbilirubinemia
- i. Generally
- due to defective transport or defective bilirubin conjugation within the liver
- itself
- 1.
- Conjugating fine but decreased bilirubin
- transport into the hepatocyte
- 3.
- Causes an accumulation of indirect bili
iii. Criger-Najjar
- 1.
- Hereditary deficiency in UDPG (necessary for
- conjugation)
- 1.
- Due to hepatitis, cirrhosis, toxins, etc.
- 2.
- AST and ALT- liver enzymes that indicate
- hepatocellular inflammation and damage often elevated
- 3.
- Bili results can vary depending on severity of
- damage
- b.
- All enz can be increased, but AST & ALT
- elevations are more pronounced
-
Post-hepatic hyperbilirubinemia
- i. Generally
- due to defect in transporting conjugated bili and bile out of the liver
- ii. Often
- called “obstructive jaundice” b/c can involve obstruction of the small
- canaliculi within the liver, the hepatic bile duct, the common bile duct, or
- gallbladder
- 1.
- Obstruction due to gallstones, scarring, nodules
- from cirrhosis, or tumors
- 2.
- If stones not resolved, bacterial growth can
- cause septicemia
- b.
- GGT and ALP- enz that indicate biliary cell
- damage are often elevated
- c.
- Stools lose color, which is indicative of low
- urobilinogen
- d.
- Pronounced elevations of ALP and GGT
- e.
- Normal to slightly increased AST & ALT
-
Neonatal hyperbilirubinemia
- i. Not
- always caused by liver function
- ii. Most
- commonly caused by a short-term in producing UDPG
- iii. Also,
- higher turnover of neonatal RBCs as fetal hemoglobin F is replaced by A
- iv. Longer
- more sustained hyperbili indicates serious condition such as
- 1.
- Hemolytic Disease of the Newborn (HDN)
- a.
- Presents as a pre-hepatic jaundice
- (incompatibility btwn blood groups of mother an fetus)
- 2.
- Biliary atresia- anatomical obstruction of
- biliary ducts
- v. Other
- factors such as progesterone or other hormones in breast milk my suppress
- conjugation
- b.
- Phototherapy often treatment to prevent
- kernicterus
- i. UV
- light converts bili to isomer which is water soluble and excretable
- c.
- Normally subsides in a few weeks
-
Liver enzymes
- a.
- AST (aspartate amino transferase) (SGOT)
- b.
- ALT (alanine amino transferase) (SGPT)
- c.
- GGT (gamma glutamyl transferase)
- d.
- ALP (alkaline phosphatase)
- e.
- LD (lactate dehydrogenase)
- i. AST,
- ALT, & LD are mainly found in structural hepatic cells
- ii. ALP
- & GGT are more concentrated in the biliary ducts or canaliculi
- f.
- Measurement in enz aid in diagnosis and
- treatment
- g.
- Enz are released into plasma at higher rate than
- normal when cells become diseased
- h.
- Diff tissues can release diff enz depending on
- location
-
Isoenzymes
- a.
- Multiple forms of the same enz composed of diff
- subunit strux and are distributed in diff types of tissues
- b.
- In addition to being found in the liver:
i. AST: erythrocyte and muscle tissue
- ii. LD:
- erythrocyte and muscle tissue
- iii. ALP:
- osteoblast, intestinal mucosa, and placental tissue
- iv. ALT:
- only found in the liver, therefore most lliver specific
-
Synthetic activities of the liver
- i. Liver
- synthesizes majority of proteins in the plasma
- 1.
- Measurment can be indicative of liver function
- 2.
- Also indicative of malnutrition, renal loss, and
- gastrointestinal loss
- a.
- Liver also synthesizes carbs & lipids
- ii.
- Gluconeogenesis from a.a., alcohols, and lipids
- b.
- Formation and metabolism of fat
- ii.
- Conversion of acetyl CoA to fatty acids,
- triglycerides, and cholesterol
-
what are proteins in aqueous solution
Proteins are ampholytes in aqueous solution
- Property
- exploited in electrophoresis
-
Fiberous proteins
- string like construction usually function as structural
- components (fibrinogen, collagen, elastin)
-
Spherical proteins
- usually found in plasma and function as transporters, antigens, Ab’s,
- hormones, enzymes, and clotting factors
-
can liver produce both fibrous and spherical proteins
liver capable of producing both types
-
proteins found in protein measurement
- five classes determined by
- electrophoretic separation
- ·
- Albumin (half of total serum proteins)
- ·
- Gamma globulins (Ig, or Ab’s)
-
Storage function of liver
- a)
- Stores all fat soluble vitamins and some water
- soluble
- b)
- Converts carotene to Vit. A
- c)
- Clearinghouse for hormones
- d)
- Transport, storage, metabolism of iron
- e)
- Vit. K (part of coagulation mechanism)
-
Detoxification reactions
- a)
- Ethanol- leading hepatic toxin
- i)
- Heavy consumption may lead to cirrhosis
- ii)
- Leading cause of morbidity and mortality in US
- b)
- Liver link between internal organs’ circulation
- and systemic blood
- c)
- Protects body form potentially harmful
- substances absorbed from the intestinal tract and toxic byproducts of
- metabolism
- i)
- Ammonia converted to urea
- ii)
- Oxidation, reduction, hydrolysis, hydroxylation,
- carboxylation, demethylation, conjugation
- iii) Conversion
- to water-soluble excretable compounds
- (1) Glutamines,
- glucuronic acid, acetate, etc combined with toxin so it can be excreted through
- the kidneys
-
Effects of acetaminophen
- a)
- Exhausts the liver’s normal route of metabolism
- b)
- Toxic metabolites kill the hepatocyte
- c)
- Half life of 4 hours, so can be used to
- monitor/asses liver damage in other drug overdoses
-
Cirrhosis
- i)
- Scarring of liver resulting in nodular
- appearance
- ii)
- Result of chronic liver inflammation
- iii) Synthetic
- ability reduced = decreased proteins and clotting factors
- iv) Portal
- hypertension due to blood blockage by scarring
- v)
- Fluid accumulation (decreased albumin)
vi) Causes
(3) Hepatitis
(4) Autoimmune
(5) Hemochromatosis
-
Reye syndrome
- i)
- Hepatic destruction after viral infection such
- as chicken pox or influenza
- ii)
- Abnormal liver funx but no increase in bili
- iii) Increased
- ammonia levels
- iv) Neurological
- complications first
- vi) Linked
- to aspirin therapy in these diseases
-
Tumors
- ii)
- 2ndary to tumors from other sites (lungs,
- pancrease, ovary)
- iii) almost
- always malignant
- iv) usually
- always linked to infection with hepatitis virus
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