Digestive System: The Liver Part A

Front 1

Gross Anatomy of the Liver

Back 1

-consists of right, left quadrant & caudate lobes which composed of fxnal unit called lobules
-falciform ligament separates R & L lobes
-sits below sternum & 5th rib
-inferior vena cava
-porta hepatis: hepatic protal vein, proper hepatic artery, common hepatic duct
-gallbladder at posterior

Front 2

Microanatomy of the Liver

Back 2

-lobules consist of rows upon rows of hypatocytes
-blood flows past hepatocytes vie sinusoids from branches of hepatic portal vein to central vein of each lobule
-inside sinusoids are hepatic macrophages called kupffer cells (remove debris-bacteria & worn out blood cells)
-tiny ducts called bile canaliculi run parallel to sinusoids & drain bie produced by the hepatocytes
-hepatocytes are arranged into hepatic cords separated by adjacent sinusoids

Front 3

Portal Triad

Back 3

1. Portal vein (branch of)
2. Hepatic artery (branch of)
3. Bile duct
4. lymphatic vessels

Front 4

Liver Sinusoidal Blood Flow

Back 4

-sinusoids are lined by fenestrated endothelium
-endothelium has NO underlying basesment mem
0fenestrations permit blood plasma to wash freely over exposed surface of hepatocytes in the SPACE OF DISSE (perisinusoidal space)
-sinusoidal blood flow is always TOWARDS the central vein

Front 5

Arterial Blood flow through the liver:

Back 5

1. Oxygenated blood from hepatic artery & Nutrient-rich, deoxygenated blood from hepatic portal vein
2. Liver sinusoids
3. Central vein
4. Hepatic vein
5. Inferior vena cava
6. Right atrium of heart

Front 6

Lymphatics and the Liver

Back 6

-plasma moves freely in spaces of Disse liver must have extremely high lymph flow to prevent accum of interstitial fluid
-if pressure rises in portal veins & sinusoids, excessive amts of fluid begin to trasude into lymph & leak thru outer surface of the liver capsule directly into ab cavity producting ASCITES
-bc extensive blood supply & lymphatics the liver is prime site of spread of cancerous cells (metastasis) esp from GI, breast & lungs

Front 7

Ascites

Back 7

-askos meaning bag/sac
-pathologic fluid accum w/in ab cavity
-healthy men have little or no intraperitoneal fluid but women may have as much as 20ml depending on phase of menstrual cycle

Front 8

1st Pass Effect

Back 8

-most drugs absorbed from GI tract that enter portal circulation & encounter the liver before they are distributed into general circulation

Front 9

Hepatobiliary Plumbing

Back 9

R/L hepatic ducts-->common hepatic duct-->common bile duct
-the sphincter of oddi regulates the flow of bile into the duodenum

Front 10

Liver Fxn

Back 10

-glycogenolysis & glycogenesis
-protein metabolism / urea synthesis
-lipid metabolism
-hormone metabolism
-iron metabolism & storage
-vitamin storage
-drug detoxification
-vit d activation pathway
-plasma protein synthesis
-synthesis of blood clotting factors
-bile synthesis

Front 11

Glycogenolysis & Glycogenesis

Back 11

-storage of glycogen allows liver to remove excess glucose from blood, store it, & return in to blood when blood glucose concentrations fall
-liver cells can typically store up to 8% of weight as glycogen (100-120g in an adult)
-muscles: glycogen is found in a much lower concentration (1-3% of muscle mass) but total amt exceeds that in liver

Front 12

Protein Metabolism

Back 12

-aa degradation occurs almost entirely in liver
-begins w/ process known as deamination (removal of amine NH2) groups from aa
-deamination rxn requires set of enzymes: aminotransferases: SGOT (serum glutamate-oxaloacetate tranaminase also called AST aspartate transaminase) & SGPT (serium glutamate-pyruvate transaminase) also called alanine transaminase ALT
-AST & ALT have dual purpose as also used to synth non-essential aa w/in liver hepatocytes
-high blood levels of ALT (SGPT) & AST (SGOT) can be indivative of liver disease

Front 13

Urea Synthesis

Back 13

-amine groups cleaved from aa converted into ammonia (NH3) or ammonium ions (NH4) then converted to urea
-all urea forms synth in liver
-ammonia accum in blood in serious liver disease and lead to hepatic coma
-after formation urea diffuses from liver hepatocytes in body fluids & excreted by kidneys
-build up of urea in blood can lead to state of azotemia or uremia which high levels of urea become toxic to variety of tissues

Front 14

Blood Urea Nitrogen (BUN)

Back 14

-Normal BUN has range of 5-26mg/dl in the adult
-elevated BUN can occur with:
>impaired renal fxn
>increased protein intake or catabolism
>GI bleeding (due to intestinal flora creating nitrogenous waste)
>dehydration

Front 15

Lipid Metabolism: formation of lipoproteins

Back 15

-formation of lipproteins
1. chylomicron pathway:
-lymph absorb from SI
-lymph drains into bloodstream
-lipoprotein lipase removes lipids from chylomicron
-lipids stored in adipocytes & liver disposes of chylomicron reminant

2. VLDL/LDL pathway
-VLDLs leaves LDL contain mainly cholesterol-->cells require cholesterol absorb LDLs by receptor-mediated endocytosis & TG removed, store in adipocytes
-liver produce empty HDL shells-->pick up cholesterol & phospholipids from tissues-->filled HDLs return to liver-->liver exretes cholesterol as bile salts

Front 16

Lipid Metabolism: Cholesterol Synthesis

Cholesterol Elimination

Back 16

HMG-CoA reductase: imp enzyme in liver hepatocytes required for endogenous cholesterol synthesis
-statin drugs inhibit endogenous cholesterol synthesis by inhibiting this enzyme

-the only way body can eliminate excess cholesterol is via BILE

Front 17

Lipid Metabolism: Ketogenesis

Hormone Metabolism

Back 17

-prim occurs in fasting states or poorly controlled DM type 1: starvation in land of plenty
-have lots of glucose but no insulin to take up, so body thinks starving--> produce ketones

-liver degrades all steroid hormones, as well as T4 & T3

Front 18

Iron Metabolism & Storage

Back 18

1. mix of Fe2+ & Fe3+ is ingested
2. stomach acid converts free Fe3+ to Fe2+
3. Fe2+ binds to gastroferritin
4. gastroferritin transports Fe2+ to SI & release it for absorption
5. in blood plasma Fe2+ binds to transferrin
6. in liver, some transferrin release Fe2+ for storage
7. Fe2+ binds to apoferritin to be stored as ferritin
8. Remaining transferrin is distributing to other organs whereas Fe2+ used to make hemoglobin, myoglobin
*iron stored in liver as ferritin

Front 19

Vitamin Storage

Drug Detoxification/Metabolism

Back 19

liver stores large quantities of VitA, B12, & D

liver is by far the most imp organ involved in drug metabolism
-most drug metabolism occurs in liver bc it has many enzyme systems (P450 being most imp)