Fisiologi

Tractus Digestivus - 2
 Ductus
hepaticus
Dextra &
Sinistra
Ductus Cysticus
Ductus Hepaticus Communis
Ductus Biliaris & Spinchter
Ductus Pancreaticus assesorius

Mucosa dgn
lipatan Cauda Pancreas
Vesica Fellea

Ductus pancreaticus
Major & Spinchter
Caput Pancreas
 Bile duct
from liver
Stomach

Duodenum
Hormones
(insulin,
glucagon)
Blood

Endocrine portion
Duct cells Acinar cells of pancreas
(secrete aqueous (secrete digestive (islets of Langerhans)
NaHCO3 solution) Enzymes)

Exocrine portion of pancreas

(acinar and duct cells)
Fig. 14-12, p.638
 Ductus : 10% pancreas
Bicarbonate
3 Sel Utama

Islet Cells :
10% pancreas
Hormon
Insulin,
Glucagon,
Somatostatin
& Pancreatic
Polypetide

Acinus : 80% pancreas

Enzym pancreas

(Stem cell pancreas)

 Sintesis, deposit & sekresi

Merubah chyme menjadi molekul-molekul yg mudah di absorpsi

1.
• 70% Disekresi dalam
bentuk Pro-Enzym yg
akan diaktifkan saat
kontak dgn mucosa
duodenum oleh
Enterokinase (brush
border glycoprotein
peptidase)
 Composition of pancreatic juice and
flow rate
Low BF: isotonic Na & Cl; High BF : isotonic Na & HCO3; Normal : isotonic
 Saat fase Cephalic &
Gastric juga terjadi
pengeluaran Pancreatic
Juice krn stimulasi n.vagus

1. Saat chyme yg bersifat asam

memasuki duodenum maka akan
menyebabkan enteroendocrine
cell mucosa duodenum
mengeluarkan Secretin.
Sedangkan makanan yg
berlemak, kaya protein akan
merangsang pengeluaran
Cholecyctokinin

2. CCK & Secretin

memasuki aliran
darah 3. Saat mencapai pancreas,
CCK akan merangsang
sekresi Pancreatic Juice yg
kaya enzym, & Secretin
akan merangsang pancreatic
juice yg kaya HCO3
 4. Stimulasi Vagus
menyebabkan kontraksi Gb
3. Garam
empedu &
Secretin yg di
sirkulasi akan
menstimulasi
produksi empedu
lebih cepat

1. Dgn masuknya Fatty

chyme yg bersifat asam
ke duodenum maka sel
enteroendocrine akan
mensekresi Secretin &
Cholecystokinine

2. CCK & Secretin

masuk ke sirkulasi
 Figure 24-27 Chemical Events in Digestion

REGION
and Hormonal Controls CARBOHYDRATES
ORAL CAVITY Salivary
amylase

ESOPHAGUS

STOMACH
Stimulus: Anticipation or
arrival of food
Hormone: Gastrin
Source: G cells of stomach Disaccharides Trisaccharides
Proenzyme released:
Pepsinogen by chief cells,
activated to pepsin by HCl

SMALL INTESTINE
Stimulus: Arrival of chyme
in duodenum Pancreatic
Hormone: CCK alpha-amylase
Proenzymes released:
Chymotrypsinogen, procar-
boxypeptidase, proelastase,
trypsinogen, Enteropeptidase
activates trypsin, which Disaccharides Trisaccharides
activates other enzymes
Enzymes released: Pancreatic
amylase, pancreatic lipase,
nuclease, enteropeptidase
Lactase Maltase, Sucrase
INTESTINAL
MUCOSA Brush border

FACILITATED
DIFFUSION AND
COTRANSPORT

Cell body
Monosaccharides

FACILITATED
DIFFUSION

ROUTE TO BLOODSTREAM Capillary

Carbohydrates and amino acids
are absorbed and transported by
intestinal capillaries. Lipids form
chylomicrons that diffuse into
lacteals and are delivered to the left Monosaccharides
subclavian vein by the thoracic duct.
 Figure 24-27 Chemical Events in Digestion
REGION
and Hormonal Controls PROTEINS
ORAL CAVITY

ESOPHAGUS

STOMACH Pepsin
Stimulus: Anticipation or
arrival of food
Hormone: Gastrin
Source: G cells of stomach Polypeptides
Proenzyme released:
Pepsinogen by chief cells,
activated to pepsin by HCl

SMALL INTESTINE Trypsin

Stimulus: Arrival of chyme Chymotrypsin
in duodenum Elastase
Hormone: CCK Carboxypeptidase
Proenzymes released:
Chymotrypsinogen, procar-
boxypeptidase, proelastase,
trypsinogen, Enteropeptidase Short peptides,
activates trypsin, which Amino acids
activates other enzymes
Enzymes released: Pancreatic
amylase, pancreatic lipase,
nuclease, enteropeptidase
Dipeptidases
INTESTINAL
MUCOSA Brush border

FACILITATED
DIFFUSION AND
COTRANSPORT

Cell body
Amino acids

FACILITATED
DIFFUSION AND
COTRANSPORT
ROUTE TO BLOODSTREAM Capillary
Carbohydrates and amino acids
are absorbed and transported by
intestinal capillaries. Lipids form
chylomicrons that diffuse into
lacteals and are delivered to the left Amino acids
subclavian vein by the thoracic duct.
 Figure 24-27 Chemical Events in Digestion
REGION
and Hormonal Controls LIPIDS
ORAL CAVITY Lingual
lipase

ESOPHAGUS

STOMACH
Stimulus: Anticipation or
arrival of food
Hormone: Gastrin
Source: G cells of stomach
Proenzyme released:
Pepsinogen by chief cells,
activated to pepsin by HCl

SMALL INTESTINE
Bile salts
Stimulus: Arrival of chyme and
in duodenum pancreatic
Hormone: CCK lipase
Proenzymes released:
Chymotrypsinogen, procar-
boxypeptidase, proelastase, Monoglycerides,
trypsinogen, Enteropeptidase Fatty acids in
activates trypsin, which micelles
activates other enzymes
Enzymes released: Pancreatic
amylase, pancreatic lipase,
nuclease, enteropeptidase
DIFFUSION
INTESTINAL
MUCOSA Brush border

Monoglycerides,
Fatty acids

Cell body
Triglycerides

Chylomicrons

ROUTE TO BLOODSTREAM Lacteal EXOCYTOSIS

Carbohydrates and amino acids
are absorbed and transported by
intestinal capillaries. Lipids form
chylomicrons that diffuse into
lacteals and are delivered to the left Chylomicrons
subclavian vein by the thoracic duct.
Organ terbesar dlm tubuh manusia yg memiliki 500 fungsi
Letak nya dibawah diafragma, kuadran kanan atas hingga area epigastrium,
dilindungi oleh costae
Memiliki 2 lobus & 2 permukaan : DIAPHRAGMATICA & VISCERALIS
Fissura
Porta hepatis
Ligamentum teres hepatis
26
Hepar mendapatkan
vaskularisasi dari 2
pembuluh darah besar yaitu :
1. Vena porta : 2/3,
membawa nutrisi
dari usus ke hepar.
2. Arteri hepatica : 1/3,
membawa oksigen
dari aorta.

Total blood flow : ± 1500

ml/menit
Fetal
circulation
 Fungsi Hepar
Metabolisme : KH, Lemak & Protein

Sekresi : Empedu

Ekskresi : Bilirubin, obat & toxin

Sintesis : Albumin, Faktor Koagulasi

Penyimpanan : Vitamin, KH, Lemak

Detoksifikasi : Toxin, Amonia

• Hepatocytes- 90% dari massa hepar & 76% dari sel dalam hepar
• Non-parenchymal cells
- Endothelial cells- 60%
- Kupffer cells- 30%
- Stellate (Ito) cells- 10%
• Banyak organella :
– Rough ER –
membuat protein
darah
– Smooth ER
membantu sintesa
garam dan
detoksifikasi toxin
dalam darah
– Peroxisomes –
detoksifikasi toxin
termasuk alcohol
– Golgi apparatus –
packages
– Mitochondria – a
lot of energy
needed for all this
– Glycosomes -
berperan dalam
penyimpanan gula
& mengatur kadar
glukosa darah

• Produksi ± 500-
1000 ml bile per
hari 35
 The hepatic artery and hepatic portal vein both connect to blood vessels
called sinusoids.
The sinusoids drain into a central vein, which feeds into the hepatic vein

Liver sinusoids
Large capillaries between plates of hepatocytes
Contribute to central vein and ultimately to hepatic veins and IVC
Carbohydrate metabolism (glucose buffering)
glycogen synthesis
polymerized from UDP-glucose
hydrolyzed by phosphorylase to glucose 1-PO4. Phosphorylase is activated by
adrenaline or glucagon via cAMP and enzyme intermediates.
represe ts up to 8% of hepato ytes’ eight

conversion of galactose and fructose to glucose

gala tose +ATP → ~ -PO ↔ UDP ~ ↔ UDP glu ose → gly oge
fru tose +ATP → ~ 6-PO ↔ glu ose 6-PO ↔ ~ -PO ↔ UDP ~
Only glucose is readily released back into blood by the action of glucose
phosphatase on glucose 6-PO4.
gluconeogenesis
• from glycerol released from fats or by deamination and conversion of
many amino-acids e.g. ala i e → pyru i a id + NH . This is pro oted y
glucocorticoids via liberation of amino-acids from protein catabolism in
peripheral tissues
Fat metabolism
oxidation of fatty acids

Trigly erides are split i to gly erol → glu o eoge esis a d fatty a ids.
Fatty acids are split by β oxidation into a shorter fatty acid, acetyl-CoA,
FADH2,
NADH and H+.
The net gain from oxidation of a molecule of stearic acid (C17H35COOH)
is 146 ATP. Acetyl-CoA can enter the TCAC or is converted to acetoacetic
acid which circulates to peripheral tissues as acetoacetic acid, β-
hydroxybutyrate and acetone (ketone bodies).
These are converted back to acetyl-CoA in cells and enter the TCAC
provided that there is adequate oxaloacetic acid (derived from
carbohydrate metabolism), otherwise ketosis develops.
synthesis of lipoproteins
The liver synthesizes VLDL, a lipoprotein containing large amount sof
triglyceride and some cholesterol and bearing the apoprotein B-100 marker.
VLDL circulates to the periphery where lipoprotein lipase hydrolyzes the
triglycerides, allowing free fatty acids and glycerol to be taken up by
peripheral tissue. The VLDL thus becomes IDL and then LDL, containing
mainly cholesterol esters. IDL and LDL are taken up by the liver and by
peripheral tissue by pinocytosis following binding of apo B-100 to its receptor.
HDL is formed in the liver and bears apo A-I or A-II on its surface. It is
thought to absorb cholesterol from vessels.
synthesis of cholesterol and phospholipids
90% of phospholipids are synthesized in the liver and
transported via lipoproteins.

They are a heterogeneous group of compounds, all containing

fatty acids and at least one phosphoric acid radical; most also
contain a quaternary nitrogen.

They include lecithins, cephalins and sphingomyelin and are

required for the formation of cell membranes, lipoproteins,
and in specialized applications such as sphingomyelin in nerve
sheaths, thromboplastin in clotting and as phosphate donors.
Cholesterol is synthesized de novo in the liver from acetyl-CoA.
The rate-limiting step in synthesis is at hydroxymethylglutaryl-CoA
reductase which is directly inhibited by cholesterol and by statin drugs.

The plasma level of cholesterol is determined partly by dietary intake and

substantially by the availability of acetyl-CoA in the liver (which is
determined by dietary saturated fat intake).

Most cholesterol in the body is in cell membranes where it affects

fluidity of the membrane and also deposits in the stratum corneum to
improve the waterproofing of the skin.

The majority of non-membranous cholesterol is converted to cholic acid

in the liver and conjugated with glycine or taurine to form bile salts which
solublize fats in the gut and are reabsorbed (enterohepatic circulation). A
small amount is used in the synthesis of steroid hormones.
synthesis of fatty acids from glucose or amino-acids
Excess acetyl-CoA can be converted to fatty acids.
acetyl-CoA + CO + ATP ↔ malonyl-CoA + ADP + PO4
3- malonyl-CoA + acetyl-CoA + NADPH + H+ → butyryl-CoA + CoA + CO2 +
2NADP+ + H2O.

This process is repeated until the fatty acid is 14-18 carbons long, when
the fatty acids are condensed with glycerol to form triglycerides.
This process is about 85% efficient in storing energy from glucose.
Triglycerides are stored in the liver or transported to peripheral fat cells via
lipoproteins.
 Protein metabolism

storage of amino acids

After absorption from the gut, amino acids are rapidly taken up by cells in the
liver and throughout the body by active transport and facilitate diffusion. They
are rapidly incorporated into proteins. Intracellular protein is in equilibrium
with free amino acids and so is readily broken down for release of amino acids
back into the circulation
transamination of aminooracids
for their metabolism.
Uptake of amino acids and synthesis of protein is promoted by GH and
insulin andamino
Nonessential antagonized by formed
acids are glucocorticoids.
in the liver
Albumin
primarily by is also
the taken up
synthesis ofdirectly by phagocytosing
the appropriate α- cells and broken
ketodown
acid to amino by
followed acids whichofare
transfer anthen released
amino radicalinto circulation
from glutamine, glutamate, aspartate or
asparagine.
gluta i e + pyru i a. → α-ketoglutamic a. +
alanine

Several of the aminotransferase enzymes which

catalyze these reactions are derivatives of
pyridoxine (B6).
deamination of amino acids

Deamination predominantly occurs by the same pathway as transamination,

with the amino radical transferred from an amino acid to α-ketoglutamic acid
and subsequent deamination of glutamine:
gluta i e + NAD+ + H O → α-ketoglutamic a. + NADH + H+ + NH3

The α-ketoacid derived from the amino acid which was deaminated can be
oxidized, usually through the TCAC.
formation of urea

The NH3 generated by deamination is toxic and

so is used to synthesize urea:
or ithi e + CO + NH → citrulline + H2O
citrulline + NH → argi i e + H O → urea +
ornithine
et: NH + CO → H N-CO-NH2 + H2O
Urea is cleared by the kidneys.
synthesis of plasma proteins

90% of plasma proteins are formed in the liver (the remainder are mainly
immunoglobulins). Albumin, fibrinogen and globulins as well as clotting
factors and some hormones are formed in the liver. The rate of synthesis is 15-
50g/day.
Human Factory
Secretion of bile
The liver secretes 600-1200 ml of bile a day. It forms in the bile
canaliculi between plates of hepatocytes and passes into
collecting ducts, hepatic ducts and the bile duct.
The lining of these ducts add volume, Na+ and HCO3 - to the bile
in response to secretin.
Some empties directly into the duodenum and the remainder is
temporarily stored in the gall bladder where it is concentrated.
Bile mengandung plasma elektrolit, bile salt / garam empedu ( conjugated
bile acid),bilirubin, cholesterol, asam lemak & lecithin, yg relatif bersifat
basa.
Jika terjadi supersaturasi maka akan memicu terjadinya batu empedu.
Pengosongan empedu diatur oleh CCK.
 Metabolisme Bilirubin

uptake

conjugation

excretion
 Gallbladder*
• Bile is produced in the liver
• Bile is stored in the gallbladder
• Bile is excreted into the
duodenum when needed (fatty
meal)
• Bile helps dissolve fat and
cholesterol
• If bile salts crystallize, gall stones
are formed
– Intermittent pain: ball valve effect
causing intermittent obstruction
– Or infection and a lot of pain,
fever, vomiting, etc.

* 64
Other functions
The liver stores vitamins A, D and B12.
It stores excess iron by binding with apoferritin to form ferritin, as well
as synthesizing transferrin for the transport and absorption of iron
Synthesis
Coagulation factors
Kupffer Cell
Detoxification of many drugs and metabolism of many hormones occurs in
the liver. Many compounds are oxidized or demethylated by the cytochrome
P450 system of enzymes, others are conjugated with UDP by glucuronyl
transferase, competing with bilirubin for this pathway.
Alcohol detoxification
Excretion of bilirubin
Bilirubin is derived from the breakdown of haem in tissue
macrophages. It circulates bound to albumin and is absorbed into
hepatocytes. Here it is conjugated with glucuronic acid (80%), sulfate
(10%) or other compounds and excreted by active transport into the
bile.

In the gut, some conjugated bilirubin is converted to urobilinogen by

bacteria which is reabsorbed and filtered by the kidneys, appearing in
the urine where it is oxidized to urobilin. Urobilinogen which is not
absorbed in the gut is converted to stercobilinogen and oxidized to
stercobilin.