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Flashcards in 2 - Hepatic Physiology Deck (57)
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1

If the liver is too big

It will shrink

2

If the liver is too small

It will grow

3

Bilirubin Produced By

Oxidation of Heme and Reduction of resultant bilverdin

Heme oxygenase converts Heme to Biliverdin
Biliverdin Reductase converts Bilverdin into Bilirubin

4

After C-Glycine Administration Early Peak

Ineffective Erythropoiesis

5

Conjugation of Bilirubin

To make it more soluble

6

Bilirubin

Delivered in sinusoid
Uptaken into hepatocyte
Biotransformed and secreted into biliary flow

7

Glucuronyl Transferase

Does something I don't know he did not use enough words

8

Bilirubins

Unconjugated (UCB)
Mono-Glucuronide (BMG)
Diglucuronide (BDG)

These are progressive steps

9

Bacterial Breakdown of Bilirubin

In color

Gives stool brown color

Deconjugation
Reduction
Oxidation

10

No bilirubin in stool

Clay colored stool

11

Biliary Atresia

Agenesis of common bile duct

Treat with "Cuh-sai" procedure
Sew intestine into intrahepatic bile ducts
Stool color doesn't matter much actually. Stool swatches were more for parents. What more counts is bilirubin in serum.

12

Enterohepatic Circulation of Bilirubin - In Hepatocyte dysfunction (hepatocellular)

Increased urobilinogen in urine because it is less efficiently reabsorbed by hepatocytes

13

Enterohepatic Circulation of Bilirubin - In Biliary Obstruction

Stools appear white
No urobilinogen detected in urine

14

Measurement of bilirubin in blood

=

15

Hyperbilirubinemia and Jaundice

Occur when liver fails or when other steps of the metabolism are abnormal.
Bilirubin >35μM can begin to detect jaundice clinically.
Coca Cola urine

16

Beefy Red Liver

Bile getting stuck in liver
Leads to micronodules too

17

Cause of Unconjugated Hyperbilirubinemia

Overproduction: Hemolysis or Ineffective Erythropoiesis
Impaired Uptake: Fast, Sepsis, Drugs (eg probenecid)

Impaired Conjugation:
Inherited Mutations in UGT1 - Grigler-Najjar Syndrome (Type I and Type II)
Inherited polymorphisms in UGT1 - Gilbert Syndrome

18

Cause of Conjugated Hyperbilirubinemia

Hepatocellular Diseases Cause Decreased Secretion:
Cirrhosis
Acute Hepatitis (drugs, viral, alcohol)

Pregnancy

Drugs

Inherited Diseases:
Dubin-Johnson Syndrome (ABCC2 mutation)
Rotor Syndrome (SLCO1B1 and SCLO1B3 mutations)

Biliary Obstruction:
Gallstones
Tumors
Primary Biliary Cirrhosis
Sclerosing Cholangitis

19

"Physiological Neonatal Jaundice"

Results from immaturity of ALL steps in bilirubin metabolism

Increased Production
Decreased Delivery
Decreased Uptake

High bilirubin level
BBB not great yet
Bilirubin in brain leads to kernicterus

20

Kernicterus

Brain damage due to bilirubin deposition

21

Treatment of Neonatal Jaundice

Phototherapy
Biliblankets or Bililight
Convert Natural Bilirubin to Photobilirubin (can pee out)

22

Jaundice

At "50", you can glow in the dark

23

Plasma proteins secreted by liver

Albumin
Clotting Factors
Antithrombin III
α-1-antitrypsin
Ceruoloplasmin
Complement C3
C-reactive protein
α-1-fetoprotein
fibrinogen
Haptoglobin
Hemopexin
α-lipoprotein
β-lipoprotein
α-2-macroglobulin
Orosomucoid
Other clotting factors
Prothrombin
Transferrin
IL-6

24

Factor VIII Level tells us

High = Liver Failure
Low = DIC

25

Clotting Factor tests

PTT or INR
Responsive to Vitamin K
II, VII, IX, X, Protein C & Protein S

Gotta start heparinizing and coumadinizing them because the tests will hypercoagulabilize them? I don't understand.

26

IL-6

Regulates body temperature

27

Pathway of protein Secretion

Synthesized in ER
Golgi Network
Secretion into bloodstream

28

Prolonged Prothrombin Time

Bleeding Tendency

29

Low Serum Albumin

Edema or maybe ascites but that can be portal hypertension as well

30

Blood Supply of the Liver

Hepatic Artery - Directly from the Heart
Portal Vein - Drains the gut (FIRST PASS METABOLISM)

31

Drug and Toxin Metabolism

Oxoreductases (Cytochrome P450) - Phase I
Lead to more polar metabolites, generate active groups for transferases

Hydrolases (Phase I)
Lead to more polar metabolites for transferases

Transferases (Phase II)
Addition of groups

32

Decreased Clearence of Toxins from portal circulation

Buildup of vasodilatory molecules (NO)
Decreased systemic vascular resistance
Increased Cardiac Output

After a liver transplant, you can go into heart failure because your spotter is gone

These mechanisms relate to trying to bypass cirrhosed liver

33

Ethanol Metabolism

Acetyl Acohol to Acetate

With chronic drinking, P450 catalyzed oxidation more active
Hella hypotheses on how alcohol damages tissues

34

Carbohydrate Metabolism

Glycogen Storage & Glycolysis
Portal Circulation contains high levels of insulin and glucagon

35

Glycogen

Polymerized glucose
Stored in liver
Glycogen phosphorylase cleaves glyocgen to make glucose available during fasting

36

Epinephrine

Stimulates glycogen degradation

37

Glucagon

Stimulates glycogen degradation

38

Insulin

Stimulates glygogen synthesis

39

Gluconeogenesis

You've exhausted your glycogen storage
Form new glucose from non-carbohydrate carbon sources
Lactate
Glycerol
Most amino acids

40

Acute read-out on how well liver is doing

Lactate is the marker
Maybe acid/base metabolism too

41

Transamination

ALT and AST
Indicators of hepatocyte damage

42

Urea Cycle

Elimination of Excess Nitrogen (Urea)
Occurs in Liver, Kidney, Striated Muscle

43

When you don't clear ammonia and nitrogenous metabolites

Hepatic Encephalopathy
Build-up of neurotoxins (nitrogen-based)
Patients become confused, obtunded, brain swelling, herniation, death

44

Physical exam - Sign of hepatic encephalopathy

Asterixis!

45

Fatty Acid Synthesis

Happens in cytosol

46

Fatty Acid β-Oxidation

Happens in mitochondria

47

Carnitine palmitoyl transferase 1A (CPT1)

Conjugates fatty acids to carnitine for transfer into inside mitochondria)

48

LDL Uptake by Hepatocytes

Decreased HMG CoA Reductase (target of Statins)
Increased ACAT
Decreased LDL receptors

LDL Binding > Internalization > Lysosomal Hydrolysis > Regulatory Actions

49

Familial Hypercholesterolemia

Transplant the kids before soft cheesy plaque lesions become calcified
LDLapheresis

50

Synthesis of bile salts in liver

Derive from cholesterol

51

Bile salts reabsorbed

Terminal ileum
Need it out before it hits the colon

52

Bile Salts

Start with cholesterol, end with bile salts

53

Enterohepatic Circulation

Important pathway he explained too fast

54

Primary Bile Acids

Converted to secodnary bile Acids in the intestin, and secondary to tertiary in the liver again

55

PFIC

Progressive Familial Intrahepatic Cholestasis
Hella itchy
Treat by bypassing terminal ileum through resection or through connecting gall bladder to skin so bile drains out of body. Gotta watch fat soluble vitamins ADEK if you do that though

56

BSEP

Important in 2 situations:

Dysfunction in sepsis - reason for elevated bilirubins
PFIC Type 2 - Increased bile salts and de

57

Other important metabolic activities of the liver

Heme biosynthesis (in infancy)
Hematopoiesis in utero
Iron metabolism
Copper metabolism
Vitamin A storage
Vitamin D metabolism