GI PHYSIOLOGY · INTERACTIVE INFOGRAPHIC 01 / GASTRIC EMPTYING

THE STOMACH AS A METERING VALVE

The Gastric
Gate

A meal is not dumped into the intestine. It is stored, ground and released at 1–4 kilocalories a minute by a pump, a sieve and a feedback brake.

1–4kcal / mindelivery set point
1–2mmparticle limitpyloric sieve
3/minslow wavesantral pace
~200kcal / hclassic figure
VAGOVAGAL BRAKE · SLOWS THE PUMP 1 MOUTH entry 2 STOMACH store · grind 3 PYLORUS meter 4 DUODENUM sense · brake 5 JEJUNUM absorb
1Mouth →2Stomach →3Pylorus →4Duodenum →5Jejunum

↩ vagovagal brake · slows the pump

01

Three machines in series

Store, grind, meter. Each region has its own muscle behaviour, pacemaker and job.

A B C D CHYME → PYLORUS → DUODENUM
A

Fundus reservoir

Tonic muscle. Accommodates 10–15× without a pressure rise. Vagovagal, NO-dependent relaxation.

B

Antrum grinder

Phasic waves at ~3/min, paced by ICC. Triturates solids and retropels them against a closing pylorus.

C

Pylorus valve

Tonic + phasic resistance. Highest nNOS in the gut. Closes as the antral wave arrives.

D

Duodenum sensor

Open endocrine cells and vagal endings sample fat, acid, osmolality, protein and stretch.

FLOWΔP / RThe stomach changes both the pressure and the resistance.
02

The 2 mm rule

Solids are not emptied. They are ground until they fit.

LAG PHASE10–20 min

Intact solids wait while the antrum grinds. Indigestible solids wait longer — for phase III of the migrating motor complex.

3contractions
per minute
1–2mm largest
particle
90%emptied by
~4 hours
TWO KINDS OF SOLIDS
Digestibleground below 2 mm · empties with the meal
Indigestibleretained · cleared by phase III MMC
TIME COURSE
0LAG 10–20 minLINEAR EMPTYING 3–4 h4 h
03

Four meals, four curves

The shape of the emptying curve tells you what is limiting: volume, calories or particle size.

Watert½ ~12 min
ExponentialVolume-limited
Glucose drinkt½ ~43 min
Near-linearCalorie-limited
Mixed mealt½ ~75 min
Lag, then linearSize + calories
High-fat mealt½ ~96 min
Long lag, slowFat brake
volume-limited calorie-limited trituration + calories Curves are schematic power-exponential fits. 0–240 min; 0–100 % remaining.
04

The duodenal brake

Five signals from the first 25 cm of intestine converge on one output: slow the stomach.

LOW HIGH
95/ 100
Long-chain fat

C12–C18 fatty acids; C≤10 are largely inert. Sustained, calorie-proportional.

Relative potency per kcal — a qualitative ranking, not a measured constant.

NO CALORIE RECEPTOR

The gut infers energy from osmolality, digestion products and calcium binding. That is why fat, protein and carbohydrate converge on a similar caloric rate through different receptors.

05

The hormone dashboard

Enteroendocrine cells turn nutrients into hormones. The arrow is the effect on gastric emptying.

CCKI cell
↓
CCK1R

Slows emptying. Gallbladder contraction, pancreatic enzymes, vagal satiety.

GLP-1L cell
↓
GLP1R

Slows emptying, amplifies insulin, signals satiety. The target of semaglutide.

PYY 3–36L cell
↓
NPY2R

The ileal brake. Released by distal nutrients; acts on vagal afferents.

GIPK cell
↔
GIPR

Does not inhibit human emptying. The old name — gastric inhibitory polypeptide — is a misnomer.

GhrelinX/A cell
↑
GHSR

The exception: accelerates emptying and drives hunger.

MotilinEnteric
↑
MLNR

Drives phase III of the migrating motor complex — the housekeeping wave.

EVIDENCE-WEIGHTED HIERARCHY
Long-chain lipid / calories
Acid
Hyperosmolality
Protein hydrolysates
Distension
Simple carbohydrate
06

The sensing wall

Open endocrine cells sample the lumen at their apex and release hormones from their base. Receptors sit on both faces.

TRACE A LIGAND

Swipe to see all eight cell types

LUMEN · CHYME
LAMINA PROPRIA · BLOOD · VAGAL ENDINGS
▲ apical · lumen ▼ basolateral · interstitium Gαq/11 Gαs Gαi/o transport / channel All sensors shown.
07

Receptor atlas

Every sensor on the wall, with its ligand, coupling, face and consequence.

Swipe to see all columns

LigandReceptor · geneCellCouplingFaceConsequence

HGNC symbols with legacy names in brackets. Evidence is predominantly murine unless marked; see panel 12.

08

Signal wiring

Five ways a receptor becomes a hormone. Coupling determines the second messenger; the second messenger determines the output.

Gαq/11
FFAR1FFAR4CaSRCHRM3 →PLCβ→IP₃→Ca²⁺→vesicle
fast · oscillatory
Gαs
GPR119GPBAR1HRH2 →adenylyl cyclase→cAMP→PKA→priming
potentiates Ca²⁺
Gαi/o
SSTR1–5FFAR3HRH3α-gustducin →↓ adenylyl cyclase→↓ cAMP→↓ Ca²⁺
brake
Transport
SGLT1PepT1 →depolarisation→Caᵥ1.2 / 1.3→Ca²⁺→vesicle
no GPCR needed
Taste cassette
TAS1R2/3TAS2R →GNAT3→PLCβ2→IP₃→TRPM5→Na⁺
clear in tuft cells
Graded, not binary. Ligand occupancy sets the calcium amplitude; calcium sets action-potential frequency; frequency sets how many vesicles fuse. Co-activation is supra-additive — FFAR1 + GPR119, or SGLT1 + GPR119, release more than the sum of either alone.
09

The reflex loop

The brake is a closed loop, not a one-way signal: duodenum → brainstem → vagus → stomach.

Swipe to see the whole loop

DUODENAL SENSORS EECs · vagal endings NTS → DMV brainstem EFFERENT VAGUS ACh · NO · VIP STOMACH antrum · pylorus glutamate GABA · TRH ACh NO · VIP 1–4 kcal / min DELIVERY SET POINT
10

By the numbers

3/min

gastric slow waves

ICC pacemaker
1–2mm

pyloric sieve

larger particles retropelled
200kcal/h

classic delivery rate

range 1–4 kcal/min
10–20min

solid lag phase

trituration time
60–90min

mixed-meal half-time

scintigraphy / breath test
~10min

duodenal brake constant

model time constant
11

When the gate fails

The same valve can run too slow, too fast, or be deliberately damped.

TOO SLOW

Gastroparesis

Symptoms plus objective delay — typically >10 % retention at 4 h. Antral hypomotility, pylorospasm, ICC and nitrergic loss.

NORMAL

Metered delivery

1–4 kcal/min, ~90 % emptied by 4 h. The brake holds delivery steady across very different meal compositions.

TOO FAST

Dumping syndrome

Reservoir or brake bypassed. Early dumping is osmotic; late dumping is reactive hypoglycaemia from exaggerated GLP-1 and insulin.

PHARMACOLOGY

GLP-1 receptor agonists deliberately push the needle left: semaglutide raised emptying half-time from ~118 to ~171 min in one study, with 37 % retention at 4 h versus none. Part of the weight-loss effect — and part of the nausea.

12

Evidence status

What is measured in humans, what is inferred from mice, and what is still unknown.

✓ Established

  • Nutrients are delivered at 1–4 kcal/min; glucose clamps near 2.1.
  • Long-chain fat is the most potent brake; C≤10 is largely inert.
  • Solids must be ground below ~1–2 mm.
  • Acid slows emptying below pH ~3.5–4.
  • CCK and GLP-1 slow human emptying; GIP does not.

~ Contested

  • Fat receptors are often drawn apical; perfusion data place them basolateral.
  • Sweet-taste receptors in EECs: clear in tuft cells, weak in primary EECs.
  • Enteroendocrine “neuropod” synapses: true contacts in <0.5 % of GLP-1 cells.
  • GLP-1R is expressed on vagal afferents, but acute agonists do not reliably fire them.

? Unknown / refuted

  • The S-cell H⁺ receptor has never been identified.
  • The duodenal osmoreceptor is unknown; it may be neural.
  • “GIP inhibits emptying” is refuted in humans — the name is a misnomer.
  • PIEZO2 in DRG (not nodose) brakes emptying: recent, single-lab.
13

Control desk

Set a meal and watch the brake hold delivery in the 1–4 kcal/min band. A teaching model, not a clinical tool.

Physical form

Hill feedback: R = Rmin + (Rmax−Rmin) / (1+(Ed/45)1.2), τ = 10 min. Acid and osmolality multiply the target.

Delivery rate—kcal / min
Energy load—kcal
Half-time—min
Time to 90 %—min
remaining energy delivery rate

A dilute glucose drink is emptied at a near-constant caloric rate: the brake holds delivery in the 2–3 kcal/min band.