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Flashcards in Liver - Anatomy Deck (28)
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1

How is the liver divided anatomically?

Physiologically?

  • Anatomic- clinically insignificant but helps to facilitate segmental resection
    • four distinct lobes: 
      • Right and left with falciform ligament btw
      • Caudate and quadrate
  • Physiologic- 8 functionally independent segments known as the french (Couinaud) system
    • each segment has its own vascular flow and biliary drainage
    • reduces M&M if resections are done by segment
    • imaging done to create 3D modes for precision

2

Describe the microscopic anatomy of the liver lobule

  • Hexagonal shape on cross section
  • 6 vertically aligned portal canals at corners and central vein at center
  • Each portal canal contains:
    • connective tissue
    • lymphatics
    • nerves
    • portal triad
      • terminal branches portal vein
      • hepatic artery 
      • bile duct

3

How does the Acinus lobule concept differ from the classic lobule?

  • Small parenchymal mass arranged around a central axis consisting of: terminal hepatic arteriole, portal venule, bile ductule, lymp and nerves
  • blood enters the center of the acinus and flows out (centrifugally) to the hepatic venules
    • bile flows opposite direction

4

What are the different zones of the Acinus lobule concept?

  • Zone 1- Periportal zone
    • cells are closest to the portal axis, receive blood that is rich in oxygen and nutrients
      • major site of oxidative metabolism and conversion ammonia to urea
    • Most prone to reperfusion injury
  • Zone 2- midzonal region
    • the arbitrary intermediary transition zone
    • "anatomic reserve"
  • Zone 3- pericentral
    • cells at margin of acinus- receive blood that has exchanged gases and metabolites with cells in zones 1 & 2 
    • least resistant to metabolic and anoxic damage
      • most prone to ischemic damage
    • major site of CYP450 and anaerobic metabolism

5

How is the liver innervated?

  • Stimulation of SNS post-ganglionic T3-T11
    • increases hepatic vascular resistance (decreased blood volume)
    • increases glycogenolysis and gluconeogenesis (increased bs)
  • Stimulation of PSNS
    • increases glucose uptake and glycogen synthesis

6

How much of the CO goes to the liver?

How many ml/min to the portal vein? Pressure?

How many ml/min to the hepatic artery? Pressure?

What arteries feed the which organs that get picked up by the portal vein? (PIC)

  • High flow with low vascular resistance
  • CO = 25-27% = 1350 ml/min
  • Portal vein- 1050 ml/min
    • 75% blood flow, 50% O2 delivery
    • pressure = 9 mmHg
  • Hepatic artery- 300 ml/min
    • 25% blood flow, 50% O2 delivery

7

How is hepatic blood flow regulated?

  • Hepatic arterioles have a myogenic response to stretching that keeps local blood flow constant, despite changes in BP
    • An increase in transmural pressure (BP) causes vasoconstriction, preventing elevation in local bf
    • decrease causes dilation, preserving perfusion
  • Autoregulation of the hepatic artery is present in metabolically active liver (postprandial hyperosmolarity)
    • usually absen in the fasted state (most OR patients)
  • Volatile agents dose-dependently decrease this response
  • pressure-flow autoregulation does not exist in the portal circulation
  • **decreases in pH or O2 or increased CO2 increase hepatic artery flow.

8

What is the hepatic arterial buffer response?

  • Changes in portal venous flow induce reciprocal changes in hepatic arterial flow
  • As portal venous flow decreases, adenosine builds up in the piriportal region
    • increases in periportal adenosine cause decreased arteriolar resistance and hepatic arterial flow increases
  • Increases in portal venous flow washes out adenosine from the periportal region, raising arteriolar resistance and lowering hepatic arterial flow

9

What are some extrinsic influences on portal circulation?

  • Tone of pre-portal splanchnic organ arterioles regulate portal vein flow
  • decreases in pH or PaO2 (portal blood) often associated with increases in hepatic arterial flow
  • postprandial hyperosmolarity increases both the hepatic arterial and the portal venous flow.

10

What are the humoral influences on portal circulation?

Which one is a good treatment for portal hypertension and esophageal varicies?

  • Hepatic arterial bed has alpha 1, alpha 2, and beta 2 adrenergic receptors
    • Epi will cause vasoconstriction (alpha receptors) and vasodilation (beta receptor)
  • Portal vein has alpha receptors only
    • Epi injected into portal vein will cause only vasoconstriction (alpha)
  • Dopamine- weak vasoactive effects compared to Epi and NE
  • Glucagon
    • dose dep relaxation of hepatic arterial smooth muscle
    • antagonizes vasoconstrictor responses of the hepatic artery to various physiologic stimuli-including increases in SNS tone

  • Angiotensin II- 

    • severely constricts hepatic arterial & portal venous beds

    • markedly ↓ both mesenteric & portal venous flow; blood flow to liver may plummet

  • Vasopressin

    • intensely constricts the splanchnic arterial bed

    • lowers portal venous resistance….. effective treatment for portal hypertension/esophageal varacies

11

How is the liver involved with Lymph?

  • 50% of lymph is made in the liver
  • sinusoidal epithelium is extremely permeable, allowing fluid and proteins into the space of Disse
    • protein content in lymph is 6 g/dl (similar to plasma)
  • Slight increase in IVC pressure (10-15 mmHg) will increase lymph up to 20x
    • sweating from liver surface causes ascites

12

What are the alterations caused by cirrhosis?

  • Liver parenchymal cells are destroyed and replaced with fibrous tissue that impedes portal blood flow through liver
  • Secondary to alcoholism, poison ingestion (carbon tetrachloride), viral disease (hepatitis), bile duct obstruction and infection

13

_____% of liver can be regenerated in animal studies.

 

Normal liver function can occur after ____% has been resected.

70% of liver can be regenerated in animal studies.

 

Normal liver function can occur after 80% has been resected.

 

**liver disease impairs ability to regenerate

14

Why is the liver considered a blood reservoir?

  • Liver is an expandable organ
  • Hepatic arteries, veins, and capillaries contain 450 ml blood (10-15% TBV)
    • with R heart failure or increased R atrial pressure, liver can accomodate up to an extra L of blood.
  • Intense SNS response can significantly decrease blood flow and expell 400-500 ml within seconds
    • Anesthetics and liver disease impair this response

15

How does liver disease affect the endocrine system?

  • altered hormone levels and diminished hepatic synthesis of hormone binding globulins with altered metabolism and receptor regulation leads to significant endocrine abnormalities
  • Insulin-like growth factor 1 (somatomedin)- mediates actions of hormones from other endocrine glands
  • Angiotensinogen- precursor to Ang II, helps w/ fluid and electrolyte balance
  • Thrombopoeitin- stimulates bone marrow precursor cells to differentiate into plts
  • T4 conversion to T3 or inactivation
  • Inactivation of: 
    • corticosteroids
    • ADH
    • aldosterone
    • estrogen
    • androgens
    • insulin
    •  

16

What is the liver's immunologic function?

  • Kupffer cells make up 10% of hepatic mass, lining hepatic venous sinuses and clean blood of toxins, abcteria, etc
    • takes <0.01 second for the bacterium to pass into the wall of the kupffer cell after coming in contact with it
    • Kupffer cell can produce and recruit inflammatory mediators/neutrophils
  • Kupffer cells are impaired in advanced disease
    • contributes to sepsis/MODS

17

How does the liver metabolize carbohydrates?

  • Maintenance of normal blood glucose concentration
    • Storage of lg amts of glycogen (75 g or 24 hrs worth)
    • Conversion of galactose and fructose to glucose
    • gluconeogenesis (from aa and triglycerides)
    • formation of many chemical compounds from intermediate products of carbohydrate metabolism

18

How does the liver metabolize lipids?

  • Beta-oxidation of fatty acids to supply energy for body
  • Cholesterol, phospholipids and lipoprotein synthesis
  • synthesis of fat from proteins and carbohydrates

19

How does the liver metabolize protein?

  • Deamination of amino acids
  • formation of urea
    • removes ammonia from bodily fluids
  • plasma protein formation
  • amino accid synthesis and interconversions
  • can produce 12-50 mg protein/day

20

What kind of vitamins does the liver store?

How much?

  • Vitamin A- 10 months worth
  • vitamin D- 3-4 months worth
  • Vitamin B12- >1 yr worth
  • Iron as ferritin- "blood iron buffer"

21

Which coagulation factors does the liver produce?

Which ones require vitamin K?

  • All coagulation factors EXCEPT vWF, VIII, III & IV
  • Vitamin K dependent: **Bile required for Vit K absorption
    • Prothrombin/Factor II
    • factor VII
    • factor IX
    • factor X
    • Proteins C and S

22

The liver produces about ___% of hem.

What part of the metabolism of hgb is the liver responsible for?

20%

Hepatocytes responsible for conjugating bilirubin and releasing it into bile and eliminated via alimentary tract

23

How much bile does the liver secrete?

  • Liver secretes 500 ml/day from common bile duct into duodenum
    • contains: conjugated bile salds, cholesterol, phospholipids, conjugated bilirubins, electrolytes
  • Bile acids help alkalinize and emulsify the large fat particles to increase surface area for digestion/aiding absorption
  • Bile is the means for excretion of waste products from blood (xenobiotics, bilirubin, Ca, and cholesterol)
  • Opioids (mu agonists) may interfere with biliary flow by increasing pressure in bile duct or causing SOOS
    • antagonized by VA, naloxone, nitroglycerine, atropine, and glucagon

24

What is the liver's role in pharmacokinetics?

  • Drugs bind to proteins synthesized by the liver which affects how the drug distributes (Vd)
  • Hepatic biotransformation = metabolism of drugs by hepatocytes changing them into inactive water-soluble substances that can be excreted and eliminated via the bile or urine
    • Phase I- hydrolysis, CYP450
    • Phase II- conjugation
  • CYP450- liver has more than 20 diff CYP enzymes
    • many oxidate drugs, environmental toxins, steroid hormones, lipids, and bile acids
    • Hepatocyte of zone 3 have the highest content of CYP proteins

25

What is the intrinsic clearance concept?

  • Intrinsic clearance reflects the fraction of the delivered drug load that is metabolized or extracted during a single pass through the liver
  • High clearance- clearance at or near rates they transverse the liver
    • lidocaine, benadryl, metoprolol
  • Low clearance- clearance independent of hepatic flow
    • diazepam, acetaminophen, warfarin
    • This is more significant when dealing with drugs that are highly protein bound

26

How is hepatocellular damage assessed?

  • AST- present with damaged liver cells, but can also be caused by other organs (heart, skeletal muscle, brain)
  • ALT- only produced by liver injury or necrosis
  • LDH-  Poor diagnostic specificity for liver disease
  • GST- found in multiple organs, sensitive indicator for liver damage
    • Best to get during a case
    • present in different tissues
    • iso-enzyme B is specific to liver
    • half life of 90 minutes- levels will quickly drop if there is no more hepatocyte damage

27

How is Bile flow assessed?

  • Alkaline phosphatase (AP) isoenzymes- generalized screening, idea about damage, but can be elevated with other normal situations
  • 5'-nucleotidase-  more specific info about if issue is extrahepatic or internal
  • Gamma glutamyl transferase (GGT)- not useful anymore
  • Serum bilirubin
    • conjugated- indicates obstruction
    • unconjugated- around surgery caused by hemolysis (lots of work to do)
      • issue with hepatocellular dysfunction
      • congenital problem

28

How can the liver's synthetic function be assessed?

good indicators of hepatic functions

  • Albumin (1/2 life 3 weeks)- half life too long to trend for acute situation
  • PT/INR (coag factor 1/2 lives 4 hours to 4 days)- better to trend for an acute situation