Case 3: Ali Khan - Cerebral Palsy + GI Conditions

GI Tract

Mouth/oral cavity

Esophagus

Stomach

Small intestine

Large intestine

Rectum + anal canal

Mouth/Oral Cavity: Palate

Hard: Anterior 2/3

Soft: Posterior 1/3

Mechanical digestion

Mouth/Oral Cavity: Teeth

Mechanical digestion

Mouth/Oral Cavity: Tongue

Skeletal muscle

• Intrinsic: Control shape

  • Innervation: CN XII

• Extrinsic: Control mobility

  • Innervation: CN XII + X

• Mechanical digestion

Papillae: Contain taste buds

Mouth/Oral Cavity: Salivary Glands

Small in mucosa

Large:

• Paired

  • Sublingual

  • Submandibular

  • Parotid

• PSNS innervation only: CN VII + IX

Secrete saliva

• Contain a-amylase + lysozymes

• Chemical digestion

Esophagus: Muscles

Skeletal: Upper 1/3

• Innervation: CN IX + X

Smooth: Lower 2/3

• Innervation: CN X

Peristalsis

Esophagus: Sphincters

Upper esophageal sphincter (UES)

Lower esophageal sphincter (LES)

Esophagus: UES

Skeletal muscle

Function:

• Normally contracted = Prevent air entering esophagus

• Relaxed during swallowing = Food enter esophagus

Innervation: CN X

Factors Hindering:

• Neurological disorders

• Age → Muscular atrophy

• Muscle fibrosis + hypertrophy

• Anticholinergics

Esophagus: LES

Smooth muscle

Function: Physiologic sphincter

• Normally contracted = Prevent stomach contents entering esophagus

• Relaxes during swallowing = Food enter stomach

Innervation: CN X + spinal nerves

Factors Hindering:

• Inhibitory neuron loss in myenteric plexus = Impaired relaxation + Increased muscle tone

  • Achalasia

  • Autoimmune destruction

  • Viral-mediated destruction

• Muscle fibrosis + hypertrophy

• Medications

  • Anticholinergics

  • Opioids

  • CCBs

  • TCA

Stomach

Muscular sack

Store + mix bolus → Chyme

Stomach: Mucosa

Contain secretory cells

Parietal: HCl + intrinsic factor

Chief: Pepsinogen

G: Gastrin

Mucous: Mucus, HCO3-, pepsinogen

Stomach: Curvature

Lesser: Attached to lesser omentum (peritoneum)

Greater: Attached to greater omentum

Stomach: Regions

Cardiac: Connect to esophagus

Fundus: Superior portion under left diaphragm

Body: Contain mucosal gastric glands

Pyloric:

• Antrum: Proximal

• Canal: Distal

Stomach: Pyloric Sphincter

Circular smooth muscle

Function: Normally contracted = Slow chyme emptying into duodenum

Innervation: CN X

Factors Hindering:

• Neurological dysfunction

• Decreased inhibitory NTs

• Muscle fibrosis + hypertrophy

• Medications

  • Anticholinergics

  • Opioids

Small Intestine: Smooth Muscle

Inner: Circular layer

• Thicker

• Folds of Kerckring: Mucosal folds = Increase SA = Increase absorption

Outer: Longitudinal layer

• Thinner

• Contract = Peristalsis

Small Intestine: Villi

Finger-like projections from folds of Kerckring

• Microvilli: Project off villi

• Increase SA = Increase absorption

  • Absorb water throughout

Intestinal Crypts of Lieberkuhn: Between villi

Capillaries: In vasa recta

Villi: Intestinal Crypts

Walls:

• Enterocytes: Secrete + reabsorb nutrients + electrolytes

• Goblet Cells: Secrete mucus

  • Protect epithelium

Base:

• Paneth Cells: 

  • Secrete antimicrobial proteins, lysozymes, phospholipase A2

    • Regulate microbiome + sterility = Innate immune defense

  • Secrete growth factors

    • Regulate crypt stem cell mitosis

• Stem Cells: Differentiate into cells → Base to tips

Small Intestine: Duodenum

Shortest

Absorb:

• Fat-soluble vitamins

• Minerals

• Simple carbs

• Amino acids

Small Intestine: Jejunum

Large diameter + thicker walls

Smaller + less folds of Kerckring 

Absorb:

• Macronutrients

• Water-soluble vitamins (B9/folate)

Small Intestine: Ileum

Longest

Small diameter + thinner walls

Larger + deep folds of Kerckring

Absorb:

• Water-soluble vitamins (B12)

• Bile salts

Ileocecal Valve: Smooth muscle sphincter connecting to cecum

Ileocecal Sphincter: Normally contracted = Slow contents entering cecum

• Opened by peristalsis

Large Intestine: Smooth Muscle

Inner: Circular layer

• Increase absorption

Outer: Longitudinal layer

• Teniae Coli: 3 bands → Bunch into haustra

• Peristalsis

Large Intestine: Cecum

Connect ileum + ascending colon

Appendix: Lymphoid tissue

Large Intestine: Colon

Segments:

• Ascending Colon: Right

  • Liver → Right colic/hepatic flexure

• Transverse Colon: Right hepatic flexure → Left colic/splenic flexure

• Descending Colon: Left

  • Descend to groin

• Sigmoid Colon

Function:

• Absorb water, electrolyte, vitamins

  • Proximal ½

• Produce + store feces

  • Distal ½

Rectum + Anal Canal

Connect to anus

Internal Anal Sphincter: Involuntary control

• Continuous with circular smooth muscle

• Normally contracted

External Anal Sphincter: Voluntary control

• Skeletal muscle

Rectum + Anal Canal: Defacation

1. Stool storage = Rectal distention

2. Threshold distension = Stretch receptors signal brain = Anal sphincters relax

3. Stool pass through

Enteric Nervous System: Description

Afferent + efferent nerve fibres controlling GI secretion + motility

• Independent from brian + spinal cord

• Modulated by SNS + PSNS

Enteric Nervous System: Contents

Enteric ganglia

Interstitial cells of Cajal (ICCs)

Enteric Nervous System: Enteric Ganglia Plexuses

Submucosal Plexus: Meissner plexus

• In submucosa

Myenteric Plexus: Auerbach plexus

• In muscularis propria (between circular + longitudinal muscle layers)

Enteric Nervous System: Enteric Ganglia NT

ACh

Dopamine

Serotonin

Enteric Nervous System: Enteric Ganglia Input

SNS:

• Prevertebral ganglia (celiac, superior mesenteric, inferior mesenteric)

• Splanchnic, hypogastric, colonic nerves

PSNS:

• Vagus nerve

• Spinal nerves (S2-4)

Enteric Nervous System: Enteric Ganglia Function

SNS Activation:

• Decrease peristalsis + secretions

• Constrict sphincters

PSNS Activation:

• Increase peristalsis + secretion 

• Relax sphincters

Enteric Nervous System: ICCs

In intestine walls

Function: Pacemaker cells = Generate spontaneous electrical waves = Rhythmic smooth muscle contractions = Peristalsis

Swallowing Phases

Phase 1: Voluntary

• Tongue push food → Pharynx (bolus)

Phase 2: Pharyngeal

• Bolus in pharynx = Activate epithelial swallowing receptors = Initiate autonomic peristaltic pharyngeal muscle contractions

• UES relax = Bolus → Esophagus

Phase 3: Esophageal

• Continue peristalsis = Relax LES = Bolus → Stomach

GI Pathologies: Delayed Gastric Emptying

Gastroparesis

Delayed Gastric Emptying: Etiology

Idiopathic (most common)

Poor glycemic control (diabetes)

Neurological disorders

• Parkinson

• MS

Connective tissue disorders

• Scleroderma

Medications:

• Opioids

• TCAs

• CCBs

• Lithium

• GLP-1 receptor agonists

• Pramlintide 

  • Amylin analog

  • Insulin therapy adjunct

Delayed Gastric Emptying: Pathophysiology

Impaired stomach relaxation during eating (accommodation)

Abnormal nerve conduction

• Electrical dysrhythmias

• Vagal nerve injury

Pyloric dysfunction

Visceral sensation

Delayed Gastric Emptying: Clinical Presentation

Nausea/vomiting

Bloating

Upper abdo pain + distension

Decreased appetite

Early satiety

Postprandial fullness

Delayed Gastric Emptying: Treatment/Management

Dietary modifications

Pharmacological

Treat underlying conditions

Delayed Gastric Emptying Treatment: Pharmacological

Prokinetics

Antiemetics

Prokinetics

MOA: Dopamine receptor antagonist = Smooth muscle contraction = Increase gastric contraction + motility and decrease sphincter tone

Ex:

• Metoclopramide: First-line

  • Adverse Effects: Tardive dyskinesia (long-term)

• Erythromycin: First-line

• Prucalopride: Second-line

  • NOT for IBD + megacolon

Antiemetics

5-HT3 antagonists

• Ex: Ondansetron

NK1 antagonists

• Ex: Aprepitant

GI Pathologies: Abnormal Autonomic Control

Enteric nervous system dysfunction

Abnormal Autonomic Control: Etiology

Stroke

Parkinsonism

MS

Diabetic neuropathy

Abnormal Autonomic Control: Pathophysiology

PSNS dysfunction (enteric neuron loss in plexuses + decreased ICCs) = Decreased peristalsis + secretions = Decreased defecation

Abnormal Autonomic Control: Clinical Presentation

Dysphagia

Constipation

Diarrhea

Fecal incontinence

Abnormal Autonomic Control: Treatment/Management

Treat underlying condition

GI Pathologies: Immobilization Pathophysiology

Inactivity = Decreased colonic mass propulsion through descending + sigmoid colon = Decreased defecation

Immobilization: Clinical Presentation

Constipation

Fecal impaction

Immobilization: Treatment/Management

Mobilization

GI Pathologies: Inadequate Oral Intake Etiology

Malnutrition

Anorexia

Dysphagia

Polypharmacy

• Opioids

• Anticholinergics

Inadequate Oral Intake: Pathophysiology

Decrease fibre + vitamin (fat-soluble + B) + fluid intake = Decreased stool bulk + slow gastric transit

Inadequate Oral Intake: Clinical Presentation

Weight loss

Constipation

Inadequate Oral Intake: Treatment/Management

Nutrient replacement

GI Pathologies: Prolonged Colonic Transit

Secondary constipation

Prolonged Colonic Transit: Etiology

Older age

Reduced mobility

GI

• Diverticulosis + diverticulitis

• Colon cancer

Neurological

• Stroke

• Neuropathy

  • Diabetic

  • B12 deficiency

• Hirschsprung disease

  • Heritable disorder 

  • No neural crest cell migration to distal colon

Metabolic

• Hypokalmeia

• Hypothyroidism

• Hyperparathyroidism

• DM 

Polypharmacy

• Fe supplements

• Ca2+ supplements

• CCBs

• Opioids

• Anticholinergics

Prolonged Colonic Transit: Pathophysiology

Altered Stool Consistency:

1. Lack of exercise, decreased fluid + fibre intake, colon changes = Slow stool passage

2. Prolong water absorption = Dry + hard stool = Irregular bowel emptying = Constipation 

Altered Bowel Motility:

1. Drugs, endocrine abnormalities, neurological pathologies = Ineffective peristalsis 

2. Difficulty passing stool (independent of consistency) = Irregular bowel emptying = Constipation

Prolonged Colonic Transit: Clinical Presentation

Abdo pain

Bloating

Constipation

Straining

Incomplete defecation sensation

Hard stool

Prolonged Colonic Transit: Treatment/Management

Nonpharmacological

• High-fibre diet

• Hydration

• Physical activity

Pharmacological

• Laxatives

• Intestinal secretagogues

Laxative Classes

Bulk-forming (fibre)

Osmotic

Stimulant/secretory

Stool softener (emollient)

Laxatives: Bulk-Forming

Ex: Methylcellulose, psyllium husks, polycarbophil

Indications: First-line (diet modifications)

MOA: Increase water absorption = Stretch bowel walls = Stimulate peristalsis

Adverse Effects:

• Bloating

• Diarrhea

• Worsen constipation

Laxatives: Osmotic

Ex: Polyethylene glucose (PEG), lactulose, sorbitol, Mg2+ salts

Indications: First-line

MOA: Draw water into intestinal lumen = Stimulate peristalsis

Adverse Effects:

• Hypokalemia

• Metabolic alkalosis

• Dehydration

• Bloating

• Diarrhea

Laxatives: Stimulant/Secretory

Ex: Senna, bisacodyl, Na+ picosulfate

Indications: + if persisting symptoms (short course)

MOA: Increase electrolyte secretion = Gastric neural depolarization = Stimulate peristalsis

Adverse Effects:

• Diarrhea

• Melanosis coli

  • Colonic hyperpigementation

Laxatives: Stool Softener

Ex: Docusate

• Not recommended

MOA: Soften stool = Easier passage

Adverse Effects: Abdo pain + cramps

Intestinal Secretagogues

Ex:

• Linaclotide

• Lubiprostone

• Plecanatide

Indications: Persisting symptoms

MOA: Increase water, HCO3-, Cl- secretion = Decrease colonic transit time

Adverse Effects:

• Diarrhea

• Nausea

Seizure: Description

Excessive + hypersynchronous activity in cortical neurons → Transient symptoms

Seizure: Classification

Focal

Generalized

• Motor

• Nonmotor

Focal Seizures

In 1 hemisphere

Symptoms:

• Motor

• Nonmotor

Awareness:

• Aware

• Impaired awareness

Generalized Seizures

In both hemispheres

Motor:

• Tonic-Clonic: Loss of consciousness + rhythmic muscle contractions

• Clonic: Muscle jerking

• Tonic: Muscle stiffening

• Myoclonic: Brief + involuntary muscle twitches

• Atonic: Muscle tone loss/reduction

Nonmotor: Absent seizures

• Typical: Brief nonconvulsive seizure

• Atypical: Longer nonconvulsive seizure

Seizures: Treatment/Management

Treat underlying cause

• Hypoglycemia

• Hyperthermia

• Electrolyte imbalances

• Alcohol withdrawal

• Meningitis

Pharmacological

Nonpharmacological

Seizure Treatment: Pharmacological

Lamotrigine

Valproic acid/valproate

Ethosuximide

Phenobarbital

Carbamazepine/oxacarbazepine

Levetiracetam

Phenytoin

Topiramate

Gabapentinoids

• Pregabalin

• Gabapentin

Seizure Treatment: Lamotrigine

Indications:

• First-line

  • Focal

  • Pregnancy

• Second-line: Generalized

MOA: Inhibit voltage-gated Na+ channels = Decrease glutamate release

Adverse Effects:

• Stevens-Johnson syndrome

  • Immune reaction causing skin blistering + epidermal detachment

• GI symptoms

• Dizziness

Seizure Treatment: Valproic Acid/Valproate

Indications:

• First-line

  • Tonic-clonic

  • Myoclonic

  • Atonic

  • Atypical absence

• Alternative: Typical absence

MOA:

• Inhibit GABA transaminase = Increase GABA

• Inactivate Na+ and Ca2+ channels

Adverse Effects:

• Tremor

• Alopecia

• Teratogenic

Seizure Treatment: Ethosuximide

Indications:

• First-line: Typical absence

MOA: Inhibit voltage-gated Ca2+ channels in thalamus

Adverse Effects:

• GI symptoms

• Skin allergy (Stevens-Johnson syndrome)

• Fatigue

• Headache + dizziness

Seizure Treatment: Phenobarbital

Indications:

• First-line: Children

MOA: GABA agonist

Adverse Effects:

• Sedation

  • Resp depression

• Induce CYP450 synthesis

Seizure Treatment: Carbamazepine/Oxacarbazepine

Indications:

• Alternative: Focal

MOA: Inhibit voltage-gated Na+ channels

Adverse Effects:

• SIADH

• Stevens-Johnson syndrome

• Induce CYP450 synthesis

• Teratogenic

Seizure Treatment: Levetiracetam

Indications:

• Alternative: Focal

MOA: Modulate GABA + glutamate release and inhibit voltage-gated Ca2+ channels

Adverse Effects:

• Fatigue

• Nausea

• Sedation

Seizure Treatment: Phenytoin

Indications:

• Alternative: Tonic-clonic

MOA: Inhibit voltage-gated Na+ channels

Adverse Effects:

• Hirsutism