GIT Physiology😍

GIT Motility

• Classified into:
• Electrical motility: Electrical activity of GIT.
• Mechanical motility: Actual gut contraction/relaxation causing movement.

Mechanical Motility 

Fasting motility:

• Migratory Motor Complex (MMC).

Fed state motility:

• In fed state: Segmentation > Peristalsis is dominant. 
1. Peristalsis: 
• Propulsive movement.
• Moves food after digestion.
2. Segmentation

Mouth → Deglutition

Swallowing / Deglutition Reflex

Stages of Swallowing

1. Oral Stage:
• Voluntary.
• The tongue moves the food backward towards the pharynx.

2. Pharyngeal Stage:
• Involuntary.
• Soft palate rises to prevent food from entering the nasal cavity.
• Epiglottis covers the laryngeal opening.

3. Esophageal Stage:
• Involuntary.
• Peristalsis

Soft palate closure mechanisms

• Soft palate elevation → Levator veli palatini

• Closure against posterior wall → Passavant’s ridge (palatopharyngeus + superior constrictor)

Deglutition Reflex Pathway

Food in Esophagus: Peristalsis

• Throughout GIT 
• Esophagus to anal canal

• Speed: 5 to 25 cm/second.

Physiologic Peristalsis:

• Food bolus → stretches GIT wall → Stretching releases Serotonin (from epithelial cells) → Acts on myenteric plexus ganglion → Starts Peristalsis

• Contraction proximally
• Acetylcholine
• Substance P.
• Cant relax when Aching (ACh) Pain (Substance P)

• Relaxation distally
• Nitric Oxide
• VIP
• Adenosine triphosphate.
• Relax after food when No (NO) VIP (VIP) At (ATP) home

Types of Peristalsis:

Clinical Aspect:

Achalasia Cardia

Chicago classification

• DCI> 8000 → Hypercontractile/Jackhammer Esophagus

• Distal latency <4s → Diffuse Esophageal spasm

Eckardt Score

• Weight loss.

• Dysphagia.

• Retrosternal pain.

• Regurgitation.

• Ekki ekki varunn → Kazhikkumbo vedana + Thiratti varum + Irakkan budhimuttu → Weight loss

Hurst phenomenon

• During barium swallow,
• lower esophageal sphinctre opens
• contents pass to stomach

• Hurst → Burst open

Treatment

• Botox:
• Highest recurrence.
• Repeated injections → Scarring.
• Restricted to elderly patients with co-morbidities.

• Heller's Myotomy:
• Laparoscopic myotomy: 6 cm proximal to 2-3 cm distal.
• Better outcome in Type I & II.
• M/C complication: GERD.
• Prevention: fundoplication.

• Pneumatic dilatation:
• Similar efficacy as myotomy.
• Indications:
• Elderly, female
• undilated esophagus, 
• Type II achalasia.

• POEM (Per-oral endoscopic myotomy):
• Best for Type III & other spastic conditions.
• Submucosal tunnelling → Muscles cut → mucosa sutured.
• ↑ Rate of esophagitis.

• Boat (Botulinum) pidich Hellil (heller) Poi (Poem)

Gastric Acid Secretion

• pH: 1.5-3 (most acidic secretions)

Pernicious Anemia

• Autoantibodies → Destroy parietal cells → Atrophic gastric mucosa→ Achlorhydria (↓↓ HCl ) → Anemia 

Acid Production in Parietal Cell

• Key components:
• a: H+/K+ ATPase proton pump.
• b: Cl-/HCO3- exchanger.
• c: Cl- channel.
• CA: Carbonic anhydrase.

• Post-prandial alkaline tide:
• Increased HCl production after a meal.
• Leads to increased HCO3 → transfer to the blood.

Functions of Gastric Secretion

• Digestion:
• Carbohydrates: 
• No enzymes involved.
• Fats: 
• Gastric lipases.
• Proteins: 
• Pepsinogen 
• Activated by HCl to become Pepsin

• Protection: 
• Increased acidity kills microorganisms.

Gastric Emptying

• Contraction/relaxation of pyloric sphincter.

• Main regulatory pathway: 
• Neural reflexes
• vago-vagal reflex

• Fastest emptying liquid: 
• Isotonic saline

• Food particle emptying rate: 
• Carbohydrate > Protein > Fat.

Gastrocolic Reflex

• Defecation in newborns, typically following a meal.

• Stomach distension→ ↑↑ colonic motility → Defecation

• ↑↑sed by: Gastrin

Hormones affecting gastric motility:

Regulation of Gastric Acid Secretion

Factors that Increase

Factors that Decrease Gastric Acid Secretion

• Excess acid: Causes negative feedback.

• Somatostatin:→ universal inhibitor.

• Prostaglandin

• Cholecystokinin

• Secretin

• Calcitonin

Small Intestine Motility

Segmentation

• Non-propulsive slow movement

• Both ends contract.
• Food moves to-and-fro in the same portion.

• Always present when food is taken.

• Aids digestion and absorption

Factors Affecting Gastrointestinal Motility

Large Intestine Motility

• Haustrations
• Combined contraction of circular & longitudinal muscles.
• Use: Absorption of water & electrolytes.

• Mass movement



• Modified peristalsis in colon
• Moves along segment.
• Dominantly seen postprandial
• Typically 3-4 times/day
• Mainly in sigmoid colon > transverse colon (controversial MCQ).

Defecation Reflex

• Control: Conscious & Voluntary.

• Mechanism:
• Rectal distension → via stretch afferent → spinal cord.
• PNS output → Relaxes internal anal sphincter
• If situation favorable:
• Powerful contractions of abdominal muscles, rectum, colon.
• Relaxation of external anal sphincter

• Muscles Involved:
• Rectal muscle 
• Involuntary
• ANS
• PNS: Relaxes
• SNS: Contracts
• External sphincter: Skeletal muscle
• Voluntary
• Pudendal nerve

• Rectal Pressure & Soiling:
• 18 mmHg: 1st urge to defecate.
• 55 mmHg: Voluntary control lost.
• Sudden, inadvertent release of IAS & EAS → Soiling.

Transit Time

Basic Electrical Rhythm (BER)

• Slow wave of GIT

• RMP of GIT smooth muscles.

• Not a fixed value.

• Fluctuates spontaneously -65 mV to -45 mV (or -40 mV)

• Pacemaker cells in GIT → Interstitial cells of Cajal →Responsible for origin of BER.

Rate of BER

• Peaks/min

• Maximum rate: 
• Duodenum (312/min)

• Minimum rate:
• Cecum (2/min) >Stomach (4/min)

• Other rates:
• Jejunum: 11/min.
• Ileum: 8/min.
• Sigmoid colon: 6/min.

• 1st Part of both is always last
• Small Intestine: Duodenum > Jejunum > Ileum > Stomach
• Large Intestine: Sigmoid colon > Caecum

• Mnemonic:
• Kajol → Duodenathil irunnu slow ayitt pelvic movement cheythu →
• Doggy (Duodenum) → Speed (maximum peaks)
• Cum (Caecum) avumbo → Slow (minimum peaks) and Stop (Stomach)
• Frquency kudiyapo tension ayi (Frequency ⇔ Tension)
• Aakki (ACh) aakki Pottarayapo (Potassium chloride) → Orgasm ayi (Spike Vannu)
• Adrenaline irangipoyapo relax ayi

BER and Contraction:

• BER itself cannot cause contraction.

• Contraction
• Spike Potential
• Occurs only when BER crosses threshold voltage.
• Threshold ≈ –45 mV for GI smooth muscle.

• Stimulation
• Acetylcholine
• KCl
• Barium chloride

• Inhibition
• Adrenaline
• Causes GIT relaxation

Spike Potential and Tension

• Tension developed ∝ frequency of spike potentials

• Spike amplitude is fixed

Migratory Motor Complex (MMC)

• Also called:
• Clearing movement
• Housekeeping movement
• Occurs every 90–120 minutes

• Rate
• 5 cm/min
• Requires ≥ 90 minutes of fasting

• Function
• Clears residual contents and food particles from GIT

• Extent
• From mid part of stomach → terminal ileum
• Seen in:
• Stomach
• Small intestine
• Not seen in large intestine

• Initiation / Regulation
• Regulated by Motilin
• Secreted by MO cells
• Location:
• Duodenum
• Jejunum
• Sometimes stomach

Erythromycin:

• Acts via motilin receptor

• Used for Rx of gastroparesis in diabetes.

GI Hormones

Classification of GI Hormones

• Gastrin family:
• Gastrin
• Cholecystokinin (CCK)

• Secretin family:
• Secretin
• Glucagon
• Vasoactive Intestinal Peptide (VIP)
• Gastric Inhibitory Peptide (GIP)

• Others:
• Motilin
• Guanylin
• Peptide YY
• Ghrelin

Enteroendocrine Cells

• Note: 
• m-cells are microfold cells of Peyer's patches (in terminal ileum).

Gastrin:

• Secreted by: 
• G cells 
• Antral region of stomach

• Most potent stimulus: 
• Peptides
• Stomach distension
• Calcium ion
• GRP

• No effect from:
• Fat, Carbohydrate

• Decrease:
• Excess acid
• Somatostatin
• GIP
• Secretin`

• Main function:
• Acid secretion from parietal cells via CCK-B receptor.
• LES contraction.
• Prevents reflux.
• ↑ Gastric motility.
• ↑ Pepsin levels.
• ↑↑ GI tract mucosal growth.

CCK - Pancreozymin

• Secreted by: I cells - small intestine

• Most potent stimulus: 
• Peptides.
• Other : Fat.

• No effect from: Carbohydrate.

• Main functions:
• Cholagogue
• Contraction of gallbladder
• Release of bile: Relaxation of Sphincter of Oddi.
• Pancreatic enzyme secretion
• CNS Actions:
• ↓ Food intake by ↑ satiety
• Inhibits gastric emptying.
• Augments action of secretin.
• Stimulates intestinal and colonic motility.
• Implicated in anxiety
• Aids in analgesia

Secretin:

• AKA natural antacid.

• First hormone to be discovered.

• Decreases enzyme concentration.

• Secreted by: S cells

• Most potent stimulus: 
• Acid.
• Other stimuli: Protein >> Fat

• No role from: Carbohydrate.

• Main function: 
• Bicarbonate secretion from pancreas
• Augments action of CCK.
• Decreases gastric acid secretion.
• Contraction of pyloric sphincter

• Secretin → Protect SI from acid attack

• Peptide everywhere

• Carbohydrate nowhere

• Fat in SI

Vasoactive Intestinal Polypeptide (VIP)

• Actions:
• Salivary glands: 
• Potentiate action of acetylcholine.
• Stomach: ↓ acid production.
• Intestine:
• ↑ Fluid and electrolyte secretions
• Relaxation of smooth muscle

VIPoma:

• Neuroendocrine tumor

• Leads to WDHA / pancreatic cholera / Verner-Morrison syndrome.

• Very Important Person → kanan pokumbo watery diarrhea

• Symptoms: WDHA
• Watery diarrhea
• Hypokalemia.
• Achlorhydria.

Gastric Inhibitory Polypeptide

• Also called Glucose-dependent Insulinotropic Polypeptide

• Secretion mechanism
• Oral glucose intake
• Stimulates K-cells
• Release of GIP
• Acts on β-cells of pancreatic islets
• → Increased insulin secretion

• Note
• GI hormones that increase insulin secretion are called Incretins
• Examples:
• GIP
• Glucagon-like peptide

Other Hormones

Motilin

• Seen in all fasting individuals.

• Causes ↑ GI motility:
• Regulates Migratory Motor Complex

Guanylin

• ↑ Cl- secretion in GI tract.

• Structurally similar to E. coli 
• Molecular mimicry

Peptide YY

• Stimulus: Fat-rich diet.

• Actions:
• ↓↓ gastric motility.
• ↓↓ acid secretion.
• Inhibits ileal motility (ileal brake).

Ghrelin

• AKA Hunger hormone

• Secretion: From oxyntic gland in stomach.

• ↑↑ during fasting.

• Levels:
• High in anorexia nervosa patients.
• Low in obese patients.

• Actions:
• Orexinergic: ↑ food intake.
• Increases:
• Gastric acid.
• Gastric motility.
• ↑ Adipogenesis.
• ↑ Release of GH: GH-RELEASING.

GI Secretions

Daily Secretion Amounts (Gayton):

• Intestinal: 1-3 liter/day.

• Stomach: 1-2 liter/day (Most volume??)

• Salivary: 1 liter/day.

• Pancreatic: 1 liter/day.

• Bile: 0.5 to 1 liter/day

• I Secrete So Perfectly By Burning

• Intestinal (3L)> Stomach (2L)> Saliva= Pancreas (1L)> Bile (0.5L) > Brunner (0.2L)

pH of Various Secretions (Important MCQ):

• Brunner's gland (Duodenum): 8-9 

• Pancreatic: 8.3.

• Salivary: 6-7.

• Stomach: Most acidic.

• Acidity
• Stomach > Saliva >Pancreas > Brunner

Electrolyte Composition (MCQs):

• K+
• Maximum concentration: 
• Colonic secretion ("C for C").
• Maximum amount secreted per day: 
• Salivary gland.

• Maximum Na and least K: 
• Bile
• Soda bile

• Maximum K and least Na: 
• Saliva 

• Maximum bicarbonate: Pancreas.

• Maximum chloride: Stomach secretion.

Salivary Secretion Electrolyte

• In salivary gland duct:
• Sodium (Na+): 
• Actively reabsorbed.
• Chloride (Cl-): 
• Passively reabsorbed 
• Due to electrical repulsion
• Sodium and chloride concentration ↑↑ → as flow increases → (? ↓ reabsorption)

• K+
• Actively secreted.
• Na+ absorption > K+ secretion
• Duct lumen becomes negatively charged.
• HCO3-
• Secreted into lume
• Partially active
• partially passive
• Coupled with Cl- reabsorption

Gastric Glands and Their Cells

Biliary Secretion

• Liver → Synthesizes bile

• Gall bladder: Stores and concentrates bile

Functions of Bile

• Digestion and absorption of lipids.

• Excretion of:
• Bile pigments.
• Cholesterol.

Constituents of Bile

• Primary bile acids
• Synthesized in liver
• Cholic acid.
• Chenodeoxycholic acid.

• Secondary bile acids
• Formed in intestine by intestinal flora
• Deoxycholic acid,
• Lithocholic acid.

• Conjugation in liver: 
• Primary bile acids are conjugated with glycine/taurines and Na 
• Form Bile salts (Sodium salts)
• E.g Sodium glycocholate salts

Enterohepatic Circulation

• Purpose: 
• Minimize energy consumption during bile synthesis.

• Cycle: 
• Bile from liver/gall bladder → Intestine → Absorbed in Terminal ileum → Via Portal vein → Liver.

• Occurs 6-8 times/day.

• Enterohepatic circulation applies to all
• except Lithocholic acid,
• undergoes least enterohepatic circulation

Factors Affecting Bile Synthesis

• Choleretic
• ↑↑ bile synthesis
• Bile salt.
• Secretin.
• Vagal stimulation.
• Mnemonic: Vagus stimulates () secretion (Secretin) of bile (Bile salts)

• Cholagogues
• Increase contraction of gall bladder
• CCK.
• Mnemonic: CCK → Compress compress

Mechanism of HCO3- Secretion

• Location: Pancreatic cell
• a: → Cl-/HCO3- exchanger.

• Intracellular Reaction:
• CO2 + H2O → H2CO3
• H2CO3 → HCO3- + H+

• CFTR
• Cystic Fibrosis Transmembrane Conductance Regulator
• Function: Chloride channel opening.
• Mutation → Cystic fibrosis.

Exocrine Pancreatic Secretion

• Pancreatic Acinar cells: 
• Secrete digestive enzymes

• Pancreatic duct cells:
• Secrete hormones

Function: Digestion

• Carbohydrates: 
• Pancreatic amylase.

• Fats: 
• Pancreatic lipase
• Assisted by co-lipase

• Proteins: 
• Zymogens (inactive enzymes): 
• Trypsinogen
• Chymotrypsinogen
• Procarboxypeptidase.

• Duodenum:
• Secrete Enterokinase/Enteropeptidase

• Activation of Zymogens
• Trypsinogen → Duodenum > Jejunum → Trypsin
• Chymotrypsinogen + Trypsin → Chymotrypsin
• Procarboxypeptidase + Trypsin → Carboxypeptidase

• NOTE
• Inflammatory process → Premature activation of zymogens → Acute pancreatitis

Intestinal Secretions

• Also known as succus entericus.

• Site: Crypts of Lieberkuhn.

Types of Cells

• Goblet cell: 
• Mucus for acid neutralization.

• Epithelial cell: 
• Source of succus entericus

• Paneth cell 
• At the base of the crypt
• ↑↑ concentration of zinc.
• Produces Defensins and Lysozymes
• Anti-bacterial

Absorption

• Water → Jejunum
• Jug il water

• Bile, B12 → Ileum
• B12 bind ileum

• Rest → CPFFI → Duodenum

• Maximum absorption sites:
• Carbohydrate, Protein, Fat: 
• Duodenum > Jejunum.
• Folic acid, Iron: 
• Duodenum > Jejunum
• Bile salts, Cobalamin ,Vitamin B12: 
• Distal ileum

• Maximum water absorption: 
• Jejunum (5.5L/day) > Ileum (2L/day) > Colon

• Fluid dynamics:
• Total fluid load in GIT/day:
• Approx. 9 liters.
• Total fluid reabsorbed
• Approx. 8.8 liters
• Water excreted in stool:
• Approx. 100 ml.