GI system

Page 1

Overview

Anatomy

Digestive Organs

Oesophagus

Stomach

Small intestine

Large intestine

Accessory Organs

Pancreas

Liver

Physiology

Motility

Digestion

Digestion

Absorption

Metabolism

Clinical Relevance

Digestion overview

Mechanical breakdown

Prehension

Mastication

Motility

Chemical breakdown

Secretion

Digestion

Absorption

Selective process

Metabolism

Egestion = defaecation

Never enters blood stream

NB excretion molecules have entered body cells then removes

Teeth

Mechanical breakdown

Salivary Glands

Secretion

Stomach

Motility

Secretion

Liver/ Gall bladder/ pancreas

Secretion

Small intestine

Motility

Digestion

Absorption

Large intestine

Motility

Fermentation

Absorption

Egestion

Digestion in the head

Physiology

Prehension

Movement of food into oral cavity

Involves use of lips, tongue and teeth as well as head movement

Mechanical breakdown

Mastication

Reduction of size of food particles

Dentition diff depending in diet

Salivation

????

Saliva

Parotid

Mandibular/ buccal/ sublingual

simple stomached

Mainly muscous saliva to lubricate passage of food

pH neutral for amylase action

Complex stomached

Mainly serous saliva to provide optimum conditions for fermentation

pH alkaline to buffer fore stomach for fermentation

Copious

Composition

Dependent on diet and which glands are stimulated

Mucin (+water = mucus)

Amylase (omnivores/horses NOT carnivores/ruminants)

Bicarbonate (neutralisation /buffering)

Phosphate (ruminants)

Lysozyme/antibodies (reduce infection)

Protein- binding tannins (leaf + bud eaters)

Urea(ruminants)

Secretion

Non ruminants

Primary secretion isotonic with blood

At low flow rates secretion becomes hypotonic

At high flow rates secretion remains isotonic

Ruminants

Secretion is always isotonic

???

Regulation

Neural control

Sympathetic - reduction in fight or flight

Parasympathetic - increase during digestion

Basal salivary secretion for oral hygiene

3 reflex pathways

Congenital

Initiated by taste/smell/presence of food in mouth

Afferent to salivary centre in brain

Efferent to salivary glands

Conditions

Pavlov dog experiments

Initted by???

Digestion in the Abdomen

Motility

Segmental contractions

Breakdown / mix

Peristaltic contractions

Movement of food in general adoral direction at a rate that allows sufficient time for digestion/ absorption

Antu-peristaltic contractions

Movement of food in an oral direction

In some species to slow down the transit of digest to allow sufficient digestion/absorption

Ruminants - allows rumination

Protective - vomiting

Mass movement

Extended peristaltic contraction used to empty sections of GI tract

Regulation for motility

Chewing / initial swallowing / defaecation under voluntary control

Intestinal contractions under involuntary control

Chemical breakdown

Secretion of digestive juices

Salivary glands/ liver/ pancreas/ glands in stomach +intestinal wall

Composition

Ions and pH appropriate for action of digestive enzymes

Mucus to lubricate food and protect mucosa

Enzymes to chemically break down food

Digestive juices extensively reabsorbed

If not - dehydration

Digestion

Chemical breakdown of food

Enzymes

Carbohydrate

Amylase, disaccharidases

Saliva/Pancreas/Inestinal mucosal surface

Protein

Pepsin???

Fat????

Absorption

Selective

Most nutrients require specific transporter proteins

Active transport

Directly by primary active transport

Indirectly by secondary active transport

Passive transport

Facilitatively via transporter protein

Diffusion down concentration gradient

Metabolism

Basic

Carbohydrate

Protein

Fat

See Running order

Page 2

Abdominal wall + Development

Layers of abdominal wall

Skin

Can be v tough depending on species

Variable cover in hair for insulation

Dense in horse ox carnivore

Minimal in pigs

Wool in sheep

Subcutaneous fascia

Superficial fascia

Contains adipose

Contains cutaneous trunk muscle

Deep fascia (Ox, horse)

Developed into a tough fibre-elastic sheet = yellow abdominal tunic

Muscles

Compromised of 4 muscles

Lateral

External abdominal oblique m.

Internal abdo obli m.

Transverse abdo m.

Ventrally

Rectus abdominis

Functions

Encloses the abdominal cavity and its contents

Motor functions

Contraction causes increase in the intra-abdominal pressure

Vomiting , defaecation and micturition

If larynx is closed also causes...?

Rectus abdominis m.

straight abdominal muscle

Origibates - ventral surface of sternalribs / sternum

Inserts on cranial border of pubis via pre pubic tendon

Left and Right sides separated by linea alba

in immature animal linea alba is pierced by umbilicus

External Oblique Abdominal m.

Outermost lateral abdominal wall muscle

Originates - lateral caudal surfaces of ribs 4+ and lumbodorsal fascia

Inserts on linea alba and prepubic tendon

Fibres run obliquely from craniodorsal to cause-ventral

Internal Oblique Abdominal m.

Middle lateral abdominal wall muscle

Originales -coxal tuber and lumbodorsal fascia

Inserts - linea alba of last rib and cartilages of causal ribs

Fibres run obliquely from caudal dorsal to craniotomy dental

Transverse Abdominal m.

????

Sheath of rectus Abdominis m.

Formed from the tendons of the lateral abdominal wall muscles

Pass above/below rectus abdominis m . to join the midline

This join is referred to as an aponeurosis and forms linea alba

SEE images

Ox has strongest muscle as more weight (heavy contents of abdomen)

Ox is less flexible

Horse more flexible -- allows jumps

Innervation

Spinal nerves T13 +L1-L5

Dorsal roots innervate dorsal musculature

Vetral roots split into 3 branches

Medial

Innermost

Runs between TA and IOA down to RA

Lateral

Runs between IOA and EOA down to midway

Lateral Cutaneous

Perforates EOA to innervate skin

Local anaesthetic used before branches off

Inguinal canal

IOM has slit (deep inguinal ring)

EOM has slit (superficial inguinal ring)

Inguinal canal = potential space between these 2 slits

Adult gastrointestinal tract

Mouth

Salivary glands

Pharynx

Oesophagus

Stomach

Liver

Duodenum

Pancreas

Jejunum

Illeum

Caecum

Colon

Rectum

Anus

Embryology

Epithileum lining GI and associated organs = endoderm

Muscle and CT = mesoderm

As embryo develops part of yolk sac taken into body

Goes on to for the gut

Midgut separated from foregut and hindgut by cranial and caudal portals

Foregut and hingut end blindly at??

???

Amniotic cavity

Allantoic cavity

Yolk sac

Stalk of yolk sac

Foregut

Midgut

Hindgut

Cranial intestinal portal

Caudal intestinal portal

Oral plate

Cloacal plate

Heart + Pericardial cavity

Endoderm

See image

Development of foregut

Enlargement of causal part of foregut identifies stomach

Oesophagus develops from gut tube between this and the pharynx

Rotation of stomach along its longitudinal axis brings axis ??

???

funds = blind ending

Longitudinal axis

Vertical axis

Dorsal mesogastrium

Stomach primordium

Oesophagus

Ventral mesogastrium

Developing liver

Duodenum

Developing spleen

Greater omentum

Lesser Omentum

Liver ligaments

Development of liver / pancreas

Endodermal diverticulum at junction of foregut and midgut becomes liver

Cranial bran??

??

Liver then expands caudally into abdominal cavity

Pancreas arises from same endodermal diverticulum

???

Blood supply to foregut + branches of celiac artery

Liver

Pericardium and heart

Dorsal primordium of pancreas

Tongue

Tracheobronchial diverticulum

Somach

Loop of midgut

Cloacal plate

Allantoic stalk

Pancreas

Liver primordium

Gall bladder

Ventral primordium of pancreas

Dorsal primordium of pancreas

Stomach

Duodenum

Development of midgut

Forms most of intestine from duodenum (?) to end of transverse colon

Connection with yolk sac reduces to form vitelline duct

?

Early growth rapid causing it to hang in elongated loop along with extensive blood supply

Rapid expansion f lier pushes midgut out of the abdominal cavity into the????

??

Physiological hesitation of midgut

Rotation of Midgut

Cranial limb elongated rapidly to form small intestine

Rotates around its arterial axis

Caudal limb puled cranially to left side

Further rotation occurs

Ca???

Further enlargement of the abdominal cavity allows the developing midgut to return to abdomen

Blood supply to midgut = branches of the cranial mesenteric artery

????

Development of hindgut

Rotation of midgut had brought hindgut to left side of abdomen

Hindgut differentiated into descending colon and rectum

A bud develops from the ventral part of the handout to form the allantois

??

??

Page 3

Canine GI Anatomy

Peritoneum

Serous membrane lining abdominal cavity + envelops abdominal organs

Single continuous sheet

Parietal peritoneum

Closely adherent to abdominal wall

Extends through inguinal canal

Visceral peritoneum

Closely adherent to organ surface

Envelops organs

Connecting peritoneum

Ligament

Connects organ to body wall/ bowel

Fold

Connects bowel organ to one another

Omentum

Connects stomach to something

Mesentery

Connects bowel to body wall

Determines movement

NB visceral = organ

bowel = intestines

Topographical anatomy

The relationship of organs within the abdomen

Cranial/caudal

Dorsal/Ventral

Middle/Left/Right

Defined by the peritoneal attachments

To one another / body wall

Aids or hinders surgical access

Cavities

Abdominal cavity

Defined by diaphragm cranially

Abdominal wall laterally

Contains all abdominal organs / structures including peritoneum

Peritoneal cavity

The potential space between parietal and visceral peritoneum

Contains nothing other than small amount of peritoneal fluid

Peritoneal inflammation = peritonitis

Diaphragm

Separates thorax from abdomen

Attaches to body wall at level of last rib

Extends to body wall at level of 5th intercostal space

Aorta passes through aortic hiatus between left and right crura

Caudal vena cava passes through canal foramen in central tendon

Oesophagus passes through oesophageal hiatus

Abdominal organs

Liver

4 lobes

Defined by blood supply = each artery supplies a lobe

L+R lobes (split into medial +Lateral in dogs)

Caudate (papillary process)

Quadrate

Gall bladder (Not all species)

Cystic/Hepatic/common bile ducts

Peritoneal attachments

Coronary ligaments = firm attachment

R+L triangular ligaments = firm attachment

Falciform / round ligaments = loose attachment

In dome of diaphragm

Cant move from position

Stomach

3 areas

Fundus = blind-ending

Corpus = body

Pylorus (pyloric antrum)

Peritoneal attachments

Greater omentum = loose

Lesser omentum

Hepato-gastric ligament

Gastro-splenic ligament

NB greater omentum used to wrap around bowel - surface for WBC if intestine contents leak

Embryonic Development

Pyloric and cardiac alway produce mucous only to protect against HCl of stomach

Omental bursa =where greater momentum fold back on itself

Spleen

On LHS of abdomen

Blood reservoir

Abnormally enlarged in barbiturate euthanasia

Peritoneal attachments

Gastro splenic ligaments

Very mobile

Duodenum

First part of small intestine

Exit of bile duct/ pancreatic duct on major duodenal papilla

Exit of accessory cut on minor duodenal papilla

Peritoneal attachments

Mesoduodenum

Duodeno-colic fold

Hepato-dudenal ligament(part of lesser omentum)

Pancreas

2 lobes

Right lobe running in craniotomy-caudal direction

Left lobe running media-laterally

Peritoneal attachments

Right lobe within mesoderm-duodenum

Left lobe within deep leaf of greater omentum

Jejunum

Middle part of small intestine

By far the largest proportion

Covered by greater omentum

Meso-jejunum

Referred to as mesentery

Fan shaped

Illeum

Terminal portion of small intestine

Enters into large intestine at cacao-colic junction

Peritoneal attachments

Ileo-caecal fold

Caecum

First part of large intestine

Blind-ending sac

In dog ileum runs directly into colon, with caecum attached on side (other species where caecum is continuous with colon and ileum enters large intestine at cacao-colic junction)

NOT the appendix in humans

Peritoneal attachments

Ileo-caecal fold

Colon

Ascending (Right)

Right colic flexure

Transverse

Passes cranial to root of mesentery

Left colic flexure

Descending (Left)

Rectum

Peritoneal attachments

Meso-colon to dorsal body wall

Page 4

Regulation

Introduction

GI tract contains sensory cells

Wall stretch

Nutrient concentration

Metabolite concentration

Osmolarity

pH

Irritation of mucous membrane

Stimulation initiates reflexes co-ordinate activity of smooth muscle and hormones

CNS also plays a part

Sight and smell of food

Regulation of appetite

Digestion mainly regulated by negative feedback mechanisms

Digestive processes co-ordinated by

Neural regulation

Hormonal regulation

Neural regulation

Reflex arcs

Short reflex arcs

Enteric nervous system

Sensory and motor nerve cells within the wall of the GI tract

Long reflex arcs

Autonomic nervous system

Sympathetic halts digestion

Parasympathetic promotes digestion

Connection between CNS

Enteric Nervous System (ENS)

Short reflex arcs located within wall of GI tract

Can operate independently of rest of body

2 nerve plexuses that synapse with each other

Sensory cells respond to

Content of lumen

Degree of wall stretch

Motor cells stimulate

Smooth muscle cells (motility)

Epithelial cells (secretion)

Simple refex arcs consist of a sensory cell and a motor nerve cell

Enable GI tract to have extensive control of its activities

Most reflexes are stimulatory

Main transmitter= acetylcholine

Other inhibitory transmitters

Complex reflex arcs consist of simple reflex arcs connected by interneurons

Nerve impulse propagated wider

ANS

Parasympathetic promotes digestion

Pre-ganglionic fibres runs in vagus

Post-ganglionic fibres embedded in wall of GI tract and connect to ENS

Cholinergic

Sympathetic nervous system

Pre-ganglionic fibres run in splanchnic nerves

Cholinergic

Post ganglionic fibres run along arteries to organ of innervation or in hypogastric nerves

Synapse with ENS or acetylcholine release at parasympathetic pre-synapses

Adrenrgic (transmitter = noradrenaline) to inhibit secretion and motility + decrease blood supply GI tract

Connection to CNS

Enero-entric reflexes

Co-ordinate activity between different parts of GI tract

Hormonal regulation

Phases of Regulation

Relate site of stimulus

Cephalic phase

Pertains to head

Anticipation of food

Emotion

Co-ordinated by ANS

Gastric phase

Pertains to stomach

Co-ordinated by ANS, ENS and hormones

Intestinal phase

Pertains to intestines

Co-ordinated by ANS, ENS and hormones

Regulation of appetite

Controlled by hypothalamus

Appetite centre (Ventro-lateral hypothalamus)

Food searching and voracious eating

Has direct effect on animals beaviour

Satiety centre (Ventro-medial hypothalamus)

Causes refusal of food

Inhibits appetite centre

Mechanism of action still unknown

3 theories

Glucostat theory - Regulated by levels of glucose

CCK theory - Regulated by levels of CCK

Lipostat theory - Regulated by levels of fat

Motility

Co-ordinated contraction of smooth muscle in GI tract

4 diff types of contraction

Segmental

Mixes lumen contents

Mechanical breakdown

Peristalsis

Move intestinal contents in a gradual aboral direction

Main type

Anti-peristalsis

Moves intestinal contents in an oral direction

Mass movement

Empties entire sections of the GI tract

In Entire GI tract operates via the same mechanism

Pace-maker cells

Repetitive + spontaneous oscillations in membrane potential occur in groups of pacemaker cells

Located between circular and longitudinal smooth muscle

Synchronisation of smooth muscle contractions achieved by transfer of oscillations to smooth muscle via gap junctions

If stimulus absence depolarisation is too weak to reach threshold potential = no muscle contraction

If stimulus present depolarisation reaches threshold potential = action potential to cause smooth muscle contraction

Action potential due to opening of Ca2+ channels

Frequency of action potential determines stength of contraction

Page 5

Stomach

Oesophagus

Swallowing (Deflutition)

Propulsion of food from oral cavity into oesophagus

Food folded into bolus by tongue and moves upwards and backwards to pharynx

Voluntary control

Forces soft palette pt o seal of nasal cavity

Pressure-sensitive sensory cells stimulated

Swallowing centre in medulla initiates swallowing reflex

Under involuntary control

Epiglottis closes of trachea

Complicated/ relaxation of muscles forces food into oesophagus

Swallowing disorders

Failure of soft palette to close off nasal cavity

Failure of epiglottis to close off trachea

Pharyngeal paralysis

Nerve/muscle injury

Botulism

Clostridial toxins block acetylcholine release

Myaestheania gravis

Antibodies formed against acetylcholine receptors

Anaesthesia

Many anaesthetic agents induce vomiting

Swallowing process impaired

Inhalational pneumonia

Anatomy

Mucosal layer

Stratified squamous epithelium

Submucosal layer

Muscular layer

Inner circular

Outer longitudinal

Composed of striated and smooth muscle (Varies according to species)

Serosal layer

Adventitia (Loose CT) only in neck

Slow healing in surgery

True serial layer in thorax

Seeimage of comparative anatomy!!!

Innervation

Sympathetic via cervical sympathetic chain

Parasympathetic ?????

Transport

Upper oesophageal sphincter closes behind food bolus

Complicated peristaltic contractions force food down oesophagus

Animals can swallow upwards

Lower oesophageal sphincter opens to allow passage of food into stomach

Lower oesophageal sphincter (Cardiac sphincter)

Physiological sphincter rather than anatomical

(Except in horses)

Always closed except during swallowing

Oesophagus enters abdomen at oblique angle

Higher pressure in abdomen cf thorax causes stomach to exert pressure on diaphragm thus re-inforcing closure

Prevents regurgitation of acidic stomach contents

Vomiting (Emesis)

Drugs stimulating vomiting = emetics

Active propulsion of stomach contents into oral cavity

Deep inspiration with simultaneous closure of trachea/ nasal cavity

Increase intra abdominal pressure via diaphragm

Forceful contraction of abdominal muscles

Cardiac sphincter opens

Food propelled up oesophagus

Upper oesophageal sphincter opens

Controlled by vomiting centre in medulla

Stimulated by phialyngeal/gastric distension or irritation

Normal in carnivores to expel bones/hair

Ruminants prefer to regurgitate

Horses and rats

Very well developed cardiac sphincter

Exaggerated oblique entry through diaphragm

Stomach usually ruptures before vomiting occurs

Gastric Torsion

Occurs in horses and dogs with wide chests

Stomach rotates 90-360 degrees

Seals off cardiac sphincter thus preventing vomiting

Stomach distends further with gas

If rotation compromises blood supply gastric tissue becomes oedematous/ hypoxic and in sever cases necrotic

Stomach dilation can impair venous return to heart via caudal vena cava resulting in circulatory shock

Extreme emergency = requiring surgical intervention

NB Torsion= twisting on its own axis

Volvulus= twisting on axis perpendicular to its own

necrotic = tissue death

Stomach

Functional anatomy

Functions of simple stomach

Digestion

Continuation of starch digestion

Initiation of protein digestion

Protection

Stomach acid kills bacteria ingested with food

Storage

Ensures food delivered to small intestine at controlled rate

Mechanical breakdown / mixing

Breaks down food and mixes with gastric juices forming a semi liquid chyme

Abomasum is rumen equivalent of simple stomach

Regions

Embryological

Oesophageal region

Non glandular

Stratified squamous epithelium

Cardiac region

????

Fundic region

Pyloric region

Anatomical

Cardia

Fundus

Corpus

Pylorus?????

Cell types

Consists of cylindrical glads

Goblet cells (Mucous)

Secrete mucus to protect against HCL

Parietal cells (oxyntic)

Secrete HCl to digest protein

Chief cells (peptic)

Secrete pepsinogen to digest protein

Entero-endocrine cells

Secrete hormones

Motility

Serves to

Prepare stomach to receive a meal

Mix and mechanically broken down

Empty stomach contents into small intestine

Prevent regurgitation of stomach contents into oesophagus

When animal starts eating there is initial relaxation of stomach smooth muscle to accommodate meal

???

Mainly peristalsis

Starts in fungus with weak contractions

Propogate down corpus

Pyloric sphincter opens to allow chyme into duodenum

When contractions reach pyloricrus the pyloric sphincter closes

????

Regulation of emptying

Mainly by strength of contraction

Also opening and closing of pyloric sphincter

Stimulation of emptying

Neural regulation - expansion of walls increases strength of contraction

Hormonal regulation - gastrin increases strength of contraction and dilates pyloric sphincter

Inhibition of emptying

Factors in duodenum ct to inhibit gastric contractions

?????

Neural regulation via increased sympathetic activity /decreas??

???

Digestion in simple stomach

Digestion is the enzymatic breakdown of nutrient macromolecules into smaller units that can be absorbed

Starch

Digested by amylase

Only active at pH >6

Protein

Digested by pepsin

Only active at low pH

Structure of starch

Complex carbohydrate

Comprises of a mixture of amylose and amylopectin

Basic unit is maltose

2 glucose molecules linked by a 1-4 alpha glycosidic bond

Amylose has a double helix

Amlyopectin

???

Starch digestion

Initiated by salivary amylase in mouth

Food doesn't spend long in mouth before swallowing

Newly swallowed food forced into centre of stomach

Acid secreted form stomach walls

Hence there is a graduated decline in pH from the centre of the stomach to edge that allows starch digestion to continue for a while

Comparative

Omniverous diets contain high levels of starch

Pigs have adapted stomachs to allow starch digestion to continue longer

Herbiverous diets contain low levels of starch

Working horse diets have increased levels of starch

Horses have adapted their stomachs to allow starch digestion to continue longer

Carniverous diets contain low levels of starch

Carnivore alive doesn't contain amylase - starch digestion occurs in small intestine

Pancreas also produces amylase

Comparison of salivary amylase

High in pigs

Low in horses as their diets usually contain low levels of starch

Absent in carnivores and ruminants

Very high in humans though we don't have???

Protein digestion

Gastric juice primarily made up of HCl and pepsinogen

Organs made of protein - so its important that pepsin is inactive until it comes into contact with foreign protein

Pepsinogen must be converted into pepsin before it can digest protein

Stomach mucosa very resistant to digestion

Breach mucosal barrier -> ulceration

Clinical signs:blood in vomit (red), blood in faeces (black)

Function of HCl

Converts pepsinogen into pepsin

Provides the required???

Secretion of HCl

See image

Duration and volume of HCl secretion depends on species

Dogs produce 0.5-1L per 24hrs cf horses 20-30L

Maximum secretion occurs 2-3 hrs after a meal in dogs cf pigs (almost continuous)

HCl secreted by parietal cells

Stomach pH reaches 2-2.5

Opposite cess occurs in pancreas to neutralise pH of food passing into duodenum

Urine pH increases just after a meal (alkaline tide) due to delay between food passing from stomach to pancreas

Blood tests may be effected

Secretion of pepsinogen

Synthesised and stored in chief cells

Secreted in inactive form (Pepsinogen)

Pepsin initiates degradation of protein and collagen by breaking peptide links adjacent to aromatic amino acids ???

??

Stimulation of secretion

Reflex arcs

Long via vagus

Short locally

3 substances

Amplify each other

Acetylcholine/Histamine

Direct stimulation

Chief . parietal and mucin cells

Gastrin

Almost entirely via stimulation of ECL cells to produce histamine

Mainly parietal cells (HCl)

Cephalic phase

Neural stimulation

???

Gastric phase

Neural stimulation

After food has entered stomach

Caused by

stomach expansion

???

Intestinal phase

After food has entered duodenum

Stimulation or inhibition

??

Stimulation via neural and hormonal signals

???

Most intestinal responses are inhibitory

Hormonal stimulation

Mediated by gastrin

Primarily in response to peptides in stomach

Reaches target cells via blood

Maximal HCl secretion requires stimultaneous stimulation by acetyl \\???

???

Inhibition of secretion

Duodenal signals inhibit motility and gastric juice secretion

Neural - vagus

Hormonal

Localised inhibit in stomach too

pH <2 stops gastrin release to protect mucous from damage

Before food enters stomach with buffers H+ reduced therefore gastrin released again

More protein in diet -> more gastrin release

Gastric /Duodenal ulceration

Stomach mucosa protected from HCl by

secretion of mucous layer

Epithelial cell membrane and interconnection tight junctions impenetrable by H+

Epithelial cells replaced every 2-3 days

Pathophysiology

Increased acid production - duodenal ulcers

Decreased protective functions (gastric ulcers)

HCl and pepsin damage epithelial cells and underlying tissue = ulceration

Damaged cells produce histamine which stimulated acid secretion and intensifies the problem

Diarrhoea occurs due to increased secretion and decreased absorption

Faeces appear very dark red/black ( blood is partially digested so appears darker)

Aetiology

Helicobacter pylori in humans

Non-steroidal anti-inflammatory drugs

??

Mast cell tumours/ Mast cell leukaemia

??

Gastrin-producing tumous

>???

Treatment

See pharmacology notes

Aimed at reducing HCL secretion

Anti-histamines

Proton pump inhibitors

Protecting ulcerated mucosa

Antacids

Mucosal binding agents

Page 6

Intestines

Digestion and absorption

SI is major site of digestion and absorption in simple stomached mammals

Absorption is selective, molecules absorbed via specific transporter proteins by

Diffusion down their concentration gradient

Secondary active transport

Most organic nutrients and monovalent ions absorbed irrespective of body requirements

Divalent ions and trace elements absorbed depending on body requirements

Small intestine has large reserve capacity

Up to 50% of SI can be resected without hindering digestion and reabsorption . NB diet would need to be adjusted

Most nutrients absorbed along whole length of SI

I.e bile salts (allows action to occur throughout duodenum and jejumum)

Absorption f some nutrients restricted to ileum

2 phases of digestion

Luminal -enzymes secreted by salivary glands/pancreas

Membranous -enzynes attached to epithelial surface of intestine

Anything remaining passes on to LI for microbial fermentation

Functional anatomy

3 parts of intestines

Duodenum (15)

Jejunum (75%)

Ileum (10%)

Standard intestinal structure

Mucosa

Submucosa

Muscle

Inner circular

Outer longitudinal

Serosa

Surface area increasesed by

Mucosal folds

Villi

Microvilli

Cell types

4 types

Goblet cells

Secrete

Mucous for lubrication and protection of mucosa

HCO3- for neutralisation

Enteroendocrine cells

Control digestive function via sensory mechanisms and release of hormones

Specialised staining needed to distinguish

Paneth cells

Possibly involved in defense against microbial penetration

Enterocytes (most)

Responsible for absorption via transporter proteins

Contain many brush border enzymes for digestion

Enzymes not secreted but remain attached to epithelial membrane

Continuous turnover of cells with migration from crypts up villus

Sloughed of at villus tip

Migration takes 2-5 days

Motility of small intestine

SI motility serves to

Mix luminal contents -segmental contractions

Propel contents down SI at rate which allows maximum absorption and digestion - peristaltic contractions

SI emptying

Circular muscle at oleo-colic junction well developed

Functions as physiological valve

Especially pronounced at ileo - caecal junction in horses

Motility of stomach increases after feeding

ileal contractions increase

ileo-colic sphincter relaxes

Facilitates emptying of SI into colon

Gastro-ileal reflex

Segmental contractions

Circular contractions occur along tended intestine

Divide intestinal contents into smaller segments

New contractions occur in centre of distended segment

Repeat many times

Mixes contents with digestive juices

Moves contents towards mucosal surface for digestion/absorption

Main type of contraction when digestion occurring

Intense contractions upon emptying of stomach

Short periods of weak segmental contractions

Allows weak peristaltic contractions to occur

BUT peristaltic contractions soon die out

Overall a slow aboral movement of chyme occurs

As chyme reaches distal SI feedback mechanism inhibits proximal SI contractions

Mediated via neural /hormonal mechanisms

Major mechanism for co-ordinating small intestinal transit to allow maximal digestion and absorption to occur

Small intestinal transit approximately 3-4hrs in most species regardless of size

Persistaltic contractions

Main type of contraction when digestion and absorption is complete

Irregular moderate peristaltic activity

Propagates a short distance before dying out

Regular strong peristaltic activity

Propagates a long distance

Each new contraction starts a little further down the small intestine

When one peristaltic contraction reaches ileum a new one starts in duodenum

Migrating myofibrils-electric complex (MMC)

Takes 1-2hrs to propagate down entire SI

Empty small intestine of contents

Prevent retrograde flow from colon

Peristalsis can occur in reverse but reverse contractions die out very quickly in small intestine

Propagation of peristalsis

Most motor neurone of ENS release Ach

Stimulates contraction of smooth muscle

Some inhibitory transmitters released too

Distension of segment causes stimulation and inhibition

Longitudinal muscle relaxes/circular muscle contracts behind chyme

Longitudinal muscle contracts/circular muscle relaxes in front of chyme

Regulation of motility

Controlledby interstitial cells of Canal (as in stomach) = pace maker cells

Spontaneous oscillations always present

?????

??

?

Primarily regulated by enteric nervous system

Presence of chyme in duodenum stimulates short reflex arcs dependent on degree of distension

Strength of contraction increased by parasympathetic / decreased by sympathetic control

Major function of ANS is to co-ordinate motility in diff parts of GI tract via long reflex arcs

Carbohydrate digestion and absorption

Provide most of energy in herbivores/omnivores

Polysaccharides

Alpha glycosidic bonds (digestible by mammalian enzymes)

Starch - straight chained maltose

Amylopectin - branched chained molecule

Glycogen - branched chained glucose

Beta glycosidic bonds (indigestible by mammalian enzymes)

Cellulose - straight chained maltose

Requires microbial fermentation

Disaccharides

Maltose (glucose + glucose)

Sucrose (glucose fructose)

Monosaccharides (Can be absorbed)

Glucose / Fructose / Galactose

Carbohydrate digestion

Only monosaccharides can be absorbed

Luminal digestive phase

starch / amylose (Amlyase) -> maltose

Salivary amylase continues digestion in stomach until acid inhibits/destroys it

Amylase digestion continues in small intestine with pancreaticc amylase

Membranous digestive phase

Maltose (maltase) -> glucose + glucose

Sucrose (sucrase) ->glucose + fructose

Lactose (lactase) -> glucose + galactose

Disaccharidases

Attached to enterocyte brush border

Maltase/Sucrase/Lactase

Digestion of maltose/sucrose very quick

Rate of absorption is limiting factor

Lactose digestion much slower

Rate of digestion is limiting factor

Disaccharidase enzyme levels change with age

Neonate - high lactase / low maltase

Adult - low lactase / high maltase

Ruminants - NO sucrase

Carbohydrate absorption

Glucose and galactose absorbed by sodium-glucose co-transporter (SGLT1)

Secondary active transport

Na+and glucose/galactose bind to transporter on luminal side

Conformational change in transporter moves Na+ and glucose into cell and release them into cytosol

High levels of Na+ in digestive juice maintain luminal concentration of Na+ high

Concentration of glucose/galactose in cytosol high so diffuse down concentration gradient into blood stream via facilitative transporter GLUT2 (passive/facilitative transport)

Fructose absorbed down concentration gradient by facilitative transporter GLUT5

Passive transport

Diffuse out of cytosol down concentration gradient into blood stream via GLUT2

Transferred to liver via hepatic portal vein

Stored as glycogen or continue in circulation to be metabolised for energy

Secondary active transport

Na+ moves from lumen into enterocyte down its conc gradient

Energy from this used to co transport glucose/ galactose

Na+ gradient maintained by Na+/K+ ATPase on basolateral membrane

Moves 3 Na+ ions out of cell in exchange for 2K+ ions

Maintains net negative charge in cell

Requires ATP

Adaption to diet

Some digestive/aborptive functions regulated by diet

Others pre-programmed to appear at certain phase of life and then disappear irrespective of diet

Omnivores

Diet contains high levels of hCHO

SGLT1 levels remain high

Expressed high throughout small intestine

Ruminants

SGLT1 expression in lambs high

As rumen develops less hHCO pass into small intestine

SGLT1 expression declines to negligible amounts in adult grazers

Maintained in intermediates/browsers as some hCHO bypasses fermentation and passes into small intestine

Horses

SGLT1 highest proximal declining distally in wild horses on grass

In order to complete domestic horses fed increased levels of hHCO

Consequently small intestine adapts by increasing levels of SGLT1 overall but especially proximally

NB hCHO- hydrolysable carbhohydrate

Lactose intolerance

Main carbohydrate in milk is lactose

Requires enzyme lactase

Lactase activity high in neonate but programmed to decline as animal is weaned

Lactase levels low/negligible in adults

EXCEPT Caucasians

In absence of lactase, lactose accumulates in gut lumen

Osmotic forse -> decreased water absorption (diarrhoea)

Once reaches large intestine fermented

Lactic acid cause pH to decline upsetting microbial balance

Lactate poorly absorbed cf VFAs - creates osmotic effect to further decrease water absorption

Gas products cause distention resulting in pain/discomfort

Protein digestion and absorption

Carniverous/ominverous diets high in protein

Herbivourous diets low in protein

However ruminant small intestine receives lots of protein in he form of microbial protein passing from rumen

Protein digestion initiated in the stomach

Continues in small intestine with pancreatic proteases

End products of digestion are di/tri-peptidases and amino acids

Most protein absorbed as di/tri-peptides

Amino acids transported into enterocytes via NA+ co-transportimilar to monosaccharides

Di/tripeptides transported into enterocytes via H+ co-transport

Transported out of enterocyte down their concentration gradient via facilitative transporters

Enzymatic digestion very fast therefore rate limiting step is absorption

Protein digestion in neonates

Proteins cannot be absorbed as intact protein as they would be regarded as foreign material and broke and evoke an immune reaction

In neonates the immune system is poorly developed

Placental transfer of maternal antibodies occurs primates, rodents, dogs, cats but not pigs, horses, ruminants

Transfer of maternal antibodies occurs via the first milk in the first 24-6 hrs

To enable absorption of intact antibodies

Epithelial cells of intestine are permeable to intact protein

Stomach produces negligible unts of HCl

Pancreatic enzyme secretion is low

Colostrum contains trypsin inhibitors

Consequently large amounts of maternal antibody (IgG) can be absorbed in the first 24hrs to provide immunity to the neonate

Comparison of protein and carbohydrate digestion

Carbohydrate

Final stage of digestion at membranous phase

Only monomers can be absorbed

Small number of enzymes required as complex CHO composed of 3 types of monomer

Protein

Final stage of digestion at luminal phase

Monomers/Dimers/Trimers can be absorbed

Large number of enzymes required as protein composed of 20 different monomers

Both

Transported via secondary active transport

Require Na+ gradient/co-transport

Fat digestion and absorption

Carnivore/omnivore Diest high in fat, herbivore diets low

BUT herbivores have capacity to absorb fat

Often added to commercial herbivore diets

Main source of fat in diets is trimming-glycerides of 16 or 18 C atoms

Plants also contain galactose-glycerides and phospholipids

Animal tissue contains cholesterol esters and phospholipids

Lipase breaks down trips-glycerides into mono-glycerides and free fatty acids

Lipase from saliva/stomach is low

Most lipase secreted in pancreatic juice

Fat digestion also requires bile salts

Bile salts

Lipase water soluble/fats are water insoluble

Digestion must occur at the water/ fat interface

Fats enter small intestine as large droplets

Bile salts reduce these droplets to a smaller size thereby increasing the SA for digestion

Bile has a water soluble + lipid soluble component

Lipid soluble part dissolves in fat droplet

Water soluble part protrudes outside the droplet

Mixing contractions of SI break fat droplets into smaller droplets

With bile these remain as small droplets

Without bile they re-coalese into large droplets

Lipase attaches to water soluble part of emulsified droplet and digests lipids within droplet

Micelles

Emulsified fat droplets too large to fit between microvilli for absorption

Bile salts aggregate together forming micelles

As micelles come into contact with emulsified fat droplets they absorb the mono-glycerides + FFAs

Micelles small enough to enter space between microvilli

Come into contact with phospholipid cell membrane + diffusion of mono-glycerides + FFAs into enterocyte occurs

Micelles then return to luminal content to absorb more mono-glycerides/ FFA from emulsified fat droplets

NB FFA- free fatty acids

Cellular metabolism of fat

Mono-glycerides/ FFAs re-esterified to form triceps-glycerides in endoplasmic reticulum

Tri-glycerides coalesce along with cholesterol and phospholipids to form chylomicrons

Exterior of chylomicron has protein coat

Allows chylomicrons to be transported in lymph and blood

Chylomicrons packaged in Golgi apparatus

Transferred to basolateral membrane and released into ECF via exocytosis

Too large to pass into capillaries therefore transported into lymphatic vessels

Transferred to blood stream without passing through liver

Fat soluble vitamins absorbed in same way

Absorption of water

Water transport occurs via 2 main rutes

Paracellular - across tight junctions between epithelial cells

Transcellular - across cell membrane via transporter proteins

Luminal membrane contains transporter proteins fro water - aquaporrins

BUT by far the largest route for water is via osmosis through Na+/glucose for amino acid transporters

Most water is re-abosrbed of digestive juice secretion (80%), the rest being from food and drink occurs principally in SI

Carnivores 90%

Ruminants 70%

Horses - most water absorption occurs in LI

Absorption of minerals

Most minerals completely absorbed irrespective of requirements

Na+ via many transporters to provide energy for secondary active transport

K+ and Cl- via diffusion, associated with absorption of other ions e.g. Na+

HCO3- Bicarbonate / chloride counter transporter

Lots of HCO3- secreted in digestive juices therefore must be reabsorbed to prevent metabolic acidosis

Trace elements

Method absorption unclear but affects each other

H3PO4

In simple-stomached duodenum pH=6 , most phosphate reabsorbed as divalent form HPO4-)

In ruminant duodenum pH4, most phosphate absorbed as monovalent form (H2PO4-)

Phosphate recycled via gut absorption/salivary secretion

Acts as rumen buffer along with HCO3- to maintain ruminal pH

Important source of nutrition for ruminal microbes

Absorption of iron

Regulated according to requirements

Secondary active transport coupled with H+ via divalent metal transporter 1 (DMT-1)

When iron low (transferrin unsaturated)

Fe2+ transferred into blood where it binds to transferrin for circulation

When iron high (transferrin saturated)

Fe2+ remains in cll bound wth apoferrritin to form ferritin

Fe3+ poorly reabsorbed

Reduced to Fe2+ by vet C or brush border enzyme ferry-reductase

Absorption of calcium

Absorbed according to body requirements

Occurs both by active and passive transport

High dietary Ca2+ increases rate of passive transport

When body calcium low or requirement high active transport stimulated by calcitrol

Increases vitamin D - dependent synthesis of calcium binding proteins

Ca2+ pumped out of cell by Ca2+ ATPase

Functional anatomy of large intestine

Major functions

Absorption

Water/ions

Fermentation

All species ferment but degree of fermentation depends on diet

Minimal in carnivores/extensive in horses

Glands in mucosa

Secrete mucous for protection/ lubrication

HCO3- to neutralise VFAs

No digestive enzymes

Only microbial digestion

Caecum

Ileum enters large intestine at junction between caecum and colon in all species except horse

Colon

Ascending (Right) /transverse/descending (Left)

Ascending is modified in the different species depending on diet

Carnivores - simple

Omnivores / Ruminants - moderate

Horses - extensive

Transverse colon passes cranial to root of mesentery

Rectum

Terminal part of colon for storage of faeces prior to evacuation

Histology

4 layers as in rest of GI tract

Mucosa

Submucosa

Muscular

Serosa

2 major cell types

Colonocytes (absorptive function)

No villi , only crypts

Microvilli (less dense than SI)

Predominate at luminal surface

Goblet cells (Secrete mucous/HCO3-)

More than SI

Predominate in crypts

Fermentation

Digestion doesn't occur in the large intestine. Fermentation of structural carbohydrate by microbes results in VFAs

Used as an energy source, especially in horse

Maintain homeostasis of colonic epithelium by regulating genes controlling proliferation/apoptosis/differentiation

Acetate

Used in liver

Oxidised in most other cells to generate ATP

Major source of acetyl CoA for lipid synthesis

Propionate

Substrate for gluconeogenesis

Volatile fatty acid can be converted into glucose

Butyrate

Energy production

Cellular homeostasis

Improves health of colon - minimises risk of colon cancer

Absorption

VFAs

Absorbed by SCFA/HCO3- exchanger

Buffers / maintains pH

Na+

Absorbed by sodium channels and Na+/H+ exchanger (NHE transporter)

Sodium absorption enhanced by aldosterone

Cl-

Absorbed by bicarbonate /hydroxyl exchange

Water

Most of rest of water passing from SI absorbed in LI

Osmotic pressure

Hydrostatic pressure

Solvent drag

Extensive reabsorption in horses

NB SCFA -Short chain fatty acids

Diarrhoea

Sufficient hydration essential for normal physiology/homeostasis

Under normal circumstances body absorbs/reabsorbs almost all water in GI tract

Diarrhoea is when water is lost in faeces through

Increased secretion

Decreased absorption

Increased water content of gut content causes distension that increases motility further reducing absorption

Pathophysiology

Nutrinal

Overload of guts capacity to absorb causes osmotic flow of water into gut lumen

Infections

Bacterial enterotoxins bind to cell membrane of intestinal epithelia stimulating cAMP in glands that results in hyper-secretion

Stress

Strong activation of parasympathetic system increases secretion and motility

Treatment

Intravenous fluids

Fluid to maintain blood volume and pressue

Ions to replace excessive secretion / insufficient reabsorption

HCO3- to counteract metabolic acidosis caused by excessive HO3- secretion / reduced reabsorption

Oral rehydration therapy

If animal drinks water alone as more water is absorbed osmotic difference between gut lumen and blood declines and prevents further water absorption

Ifanimal drinks solution containing NaCl and glucose, absorption of these nutrients causes more efficient water absorption by

Increasing the osmotic gradient between gut lumen and blood

Solvent drag through their transporter channels

Large intestine contractions

Segmental

Most common in caecum/colon

Occurs much lower frequency than small intestine

Mixing contractions with slow aboral movement of gut contents

Peristalsis

Moderate aboral movement go gut contents

Reverse peristaltic

Moderate movement of gut contents back towards mouth

More prominent in proximal colon

Retrograde flow f material back into caecum

Massmovement

Occurs in LI only

High movement f gut contents towards rectum for evacuation

Intrinsic regulation of motility

As in stomach/ SI controlled by pacemaker cells

Undergo slow oscillations

Pacemakerregion in centre of colon sends waves in both directions

Give rise to peristaltic + anti-peristaltic contractions

Pacemaker region at distal end of colon only send waves aborally

Peristaltic contraction towards rectum

Contractions ted to be strongest in pacemaker regions

inders transit of material past these regions

Extrinsic regulation of motility

LI under stronger neural influence compared to rest of gut

Parasympathetic system increases strength of contraction

Sympathetic system decreases strength of contraction

Transit of food material faster after a meal

Expansion of stomach/duodenum initiates gastro-colic reflex (long)

Sphincter between SI/LI opes

Food material forced further down GI tract

Gastrin / CCK probably also play a role to increase motility after a meal

Constipation

Aboral accumulation of food material in gut

Usually common in colon

Common dogs that have eaten bones or dry food that expands in the GI tract

Also occurs in diseased states

Prostate or anal glands

Inhibition of motility due to inflammation / pain

Megacolon

Colonic contractions weakened

As transit time delayed water absorption increased

Passage of food material made even more difficulty

Distension of colon causes pain

Treated by

Oral fluids to soften faecal material

Paraffin oils to lubricate

Drugs to strengthen contractions

Defaecation

Rectum empty most of the time

Mass movement f colon transfers faeces to rectum

Pressure sensitive cells stimulate defection reflex

Terminal colon and rectum contract

Inner anal sphincter muscle (SmM) relaxes

Outer anal sphincter muscle (StM) under conscious control in carnivores/omnivores but not horses/ruminants

Can consciously retain outer anal sphincter closed until urgency to defaecate diminishes till next mass movement contraction

Contraction of abdominal muscles helps evacuation process

Page 7

Pancreas

Functional anatomy

Microscopic structure of exocrine pancreas similar to salivary gland

Groups of acini

Simple cuboidal epithelium surrounding an excretory duct

Several excretory ducts combine with increasing dimension to terminate as pancreatic duct/ accessory pancreatic duct

Microscopic structure of endocrine pancreas consists of lots of isolated clumps of cells surrounding a capillary

2 major functions

Digestion (exocrine pancreas)

Regulation of metabolism (endocrine pancreas)

Exocrine pancreas

Principal function is digestion

Pancreatic juice has 2 major components

HCO3- to neutralise stomach acid thereby protecting small intestinal mucosa

Also provide correct pH for digestive enzymes to function

Enzymes to digest food material for absorption in the small intestine

Involved in digestion

In horse / pig substantial amounts of pancreatic juice produced to create a large intestinal environment suitable for fermentation

Equivalent to saliva production in ruminants

Ionic Composition

Pancreatic juice ionic composition similar to blood

HCO3- actively transported into duct lumen in exchange for Cl-

Water follows by osmosis

H+ correspondingly transported into blood stream

Negates the alkaline tide

At normal flow rates HCO3- reabsorbed into acing. cells

??

Table?

Enzymatic composition

Secretion of digestive enzymes for digestion

Proteases secreted in inactive form to prevent auto digestion

Trypsinogen

Amylase breaks down starch to maltose

Lipases/phospholipases break down fat to glycerol/ fatty acids

Table??

Pancreatic enzymes

Pancreatic juice contains trypsinogen

Duodenal epithelial surface contains enteropeptidase

Trypsinogen -> Trypsin

Trypsin autocatalayses itself as well as a??

?

Regulation of secretion

3 phases

Cephalic phase

Gastric phase

Intestinal phase

All 3 phases increase pancreatic juice secretion

Cephalic???

/??

Secretin

Released from duodenum in response to H+

increase HCO3- secretion

Negative feedback mechanism

As acid chyme gradually???

Cholecystokinin

Released from duodenum in response to fat / pro??

Increases enzyme secretion

Also causes gall bladder to contract

Positive feedback mechanism

?

Comparative physiology

Differences due to pattern of eating

Ruminants

Continuous flow of rumen contents into abomasum /small intestine -- pancreatic juice secretion intermittent

Carnivores / omnivores

Intermittent flow of stomach contents int small intestine - pancreatic juice secretion intermittent

Horses

Continuous flow of stomach contents into small intestine - pancreatic???

???

Endocrine pancreas

Principle function is regulation of metabolism

Clusters of cells scattered throughout the pancreatic tissue (islets of lanerhans)

1-2% of pancreatic mass

3 major types of cell

Beta

Alpha

Delta ?

Hormones

???

?

Secreted in blood stream and passes to liver via hepatic portal vein prior to circulating other tissues

Insulin

Peptide hormone released in high plasma levels of glucose and amino acids

Overall ANABOLIC effect

Produced in pancreatic Beta cells???

???

Regulation of insulin

Stimulated by increase in plasma glucose/ amino acids

Direct feedback system independent of other factors

Bi-phasic secretion

?

Also stimulated by GI hormones released when food enters duodenum

Thus insulin secreted in anticipation of ??

?

ANS regulation

Parasympathetic system increases insulin secretion ??

Sympathetic activity + adrenaline release decreases insulin secretion

Actions of insulin

Binds to receptors on target cells

?

Stimulates cell uptake of nutrients during absorptive phase

Most important anabolic mediator

Glucose uptake enhanced by mobilisation of glucose transporter (GLUT4) to cell membranes

???

Amino acid uptake enhanced by amino acid transporter proteins

Nearly all itissues

Increases intra cellular amino acids for energy and protein synthesis

Increases concentration??

???

Diabetes mellitus

Plasma glucose elevated due to decreased uptake by cells

Capacity for kidneys to re-absorb glucose exceeded

Fairly rare but occurs most often in carnivores /omnivores

2 types

Type 1 Insulin-dependent

Insulin production impaired

Treated by insulin injections

Type 2 Non-insulin-dependent

Insulin production normal but cells resistant to its effects

ISSM most common?

?

Hyperglycaemia

Results in polyuria / polydipsia

Would expect urine specific gravity to be low but artificially normal/hight due to glycosuria

Degradation of lipids increases leading to plasma FFA

Incomplete metabolism of FFAs results in production of ketone bodies

Some ketones are acidic resulting in metabolic acidosis

Impaired brain function can lead to diabetic coma / death

Hypogycaemia

Plasma glucose below normal physiological range

Most often caused by insulin overdose

Also insulinoma (tumour of pancreatic Beta cells)

Treated by oral /intravenous glucose

Ruminants less sensitive to hypoglycaemia

Glucagon

Peptide hormone released in response to decreased levels of glucose and amino acids

CATABOLIC effect

Produced by pancreatic alpha cells

Synthesised as pre-pro-hormone

???

Regulation / Actions of glucagon

Stimulated by decrease in plasma glucose and increased amino acids

Binds to receptors on target cells

Activated adenyl cyclase

Actions of glucagon are reverse of insulin

Net effect on metabolism depends on range of insulin:glucagon

Increases plasma glucose by stimulating liver glycogenolysis and gluconeogenesis

Little effect on tissues other than the liver

Page 8

Liver

Gross anatomy

Located in the dome of the diaphragm within the abdominal cavity

Basic liver has 4 lobes

Left,quadrate,right and caudate

Dog, cat pig left and right lobes split into medial and lateral parts

Caudate lobe (most species) has 2 parts- caudate and papillary processes

Lobes allow movement of organ due to diaphragm

Gall bladder

Present in carnivores, ruminants , pigs, mice

Absent in horses and rats

Histology

Liver surrounded by capsule of connective tissue

Capsule extends into liver as septa

Septae delineated the structural units of the liver - hepatic lobule

Hepatocytes

Chief function cells of liver

Absorb molecules from Space of Disse

Absorption occurs accros sinusoidal membrane

Bile canaliculus ??

Billary System

Conveys bile from liber to duodenal lumen

Secrete across hepatocyte membrane into caniliculi

Bile flows from canaliculi into ductules

Ductules anastomose into larger ducts

???

Blood supply

Hepatic portal vein

75% of blood entering liver

Hepatic artery

25% of blood entering liver

Sinusoids

Venous and arterial blood mix

Central veins

Blood from sinusoids empty into central veins

Hepatic veins

Central veins coalesce into hepatic veins

Caudal vena cava

Hepatic veins empty into caudal vena cava

Hepatic lobule

Hexagonal in shape

Lobules made of plates of hepatocytes

Hepatocytes radiate outwards from a central vein

Between the lobules are portal tracts (triads)

Bile duct

Hepatic artery

Hepatic portal vein

Hepatic Acinus

Hepatic acinus = functional unit of liver

Can be divided into zones

Zones correspond to distance from a???

??

Sinusoids

Considered as vascular channels

Lined with fenestrated endothelial cells

Surrounded by layers of hepatocytes

Macrophages (kupffer cells) patrol sinusoids

Blood flow from portal vein ./..??

Functions of the liver

Storage

Detoxification

Synthesis of cholesterol and bile salts

Synthesis of plasma proteins

Break down of RBC

??

Liver metabolism

Carbohydrate metabolism

Glycogenesis

Glycogenolysis

Gluconeogenesis

Lipid metabolism

Oxidation f fatty acids and????

???

???

Detoxification and clearance

Major role in purification, transformation and clearance

Alll substances absorbed from GI organs pass through liver via hepatic portal vein

Removes harmful substances from blood

Converts substances into less toxic compounds

Hepatocyte microsomes???

??

Drugs

Nearly all drugs are modified / degraded in liver

Conjugated or modified or excretion in urine/bile

Endogenous metabolites

Ammonia converted to urea and excreted in urine

Hormones inactivated by liver

????

Detoxification of drugs and toxins?

Examples of plant toxins

Digitalis

From foxglove

Cardia glycoside

Aflatoxin

from aspergillum fungal growth on damp grain /soybeans

Phylloerythin ????

Degradation of RBCs

RBCs removed from blood by macrophages in spleen and liver

Degraded to yield harm from haemoglobin

Haem converted to bile pigments

Haem converted to biliverdin in macrophage

Biliverdin transformed to bilirubin (yellow)

Bilirubin transported to liver in blood bound to albumin

Bilirubin conjugated with glucoronic acid in liver

Excretion of bile pigments

Bile pigments play no part in digestion = waste route for harm

Conjugated bilirubin excreted into bile

In gut bilirubin can be acted on by intestinal bacteria

Remove glucoronic acid

Metabolise bilirubin to stercobilin (brown)

This is what gives faeces its colour

Functions of bile

Promotes hydrolysis by lipase

Bile acids facilitates digestion of triglycerides by acting as emulsifying agents -render fats accessible to pancreatic lipases

Facilitates intestinal absorption of lipids

Bile acid micelles improves solubilisation and uptake of lipids

Exit route for waste products and drugs

?

Composition of bile

Water

Electrolytes

?

Biliary proteins

Bile pigments

??

Storage of Bile

Bile stored in gall bladder (if present)

Allows storage and concentration of bile

Beneficial to animals with intermittent digestion

Herbivores with continuous digestion

levels of fat in diet usually low

Horses - lack gall bladder

Ruminants have gall bladder with ineffective concentrating mechanism

Due to ??

Conjugation of bile acids

2 major bile acids synthesised from cholesterol in liver

Cholic acid

Chenodeoxcholic acid

These bile ??

???

Secondary bile acids

Following participation in lipid digestion and absorption primary ??

??

Summary of bile acids

Primary bile acids

??

Secondary bile acids

??

Bile acid secretion

Bile acids transported into bile canaliculus

?

Bile canaliculi isolated from hepatocyte cell membrane by tight junctions to prevent leakage

Bile emptied into duodenum at major ?

??

Enterohepatic circulation

Bile acids absorbed from terminal ileum by active transport

Transported back to liver by hepatic. portal vein

Efficiently captured from blood stream by liver via Na+- dependent taurocholate Co-transporting polypeptide (NTCP)

This recycling ??????

Regulation of bile secretion

Parasympathetic system

CCK

Released in response to presence of fat in duodenum

Causes contraction of gall bladder + relaxation of sphincter of Oddi

Animals without gall ballersdder have inactive sphincter of Oddi with ??

???

Also regulated by amount of nile salts returning to liver via enterohepatic circulation

During a meal presence of fat in duodenum causes release f CCK

???

Between meal lack f fat in duodenum

???

Pathophysiology of liver disease

Hepatic dysfunction and disease

Numerous causes of liver disease in animals

Infection

Poisoning

Tumours

Onset of liver disease may affect its major functions

Bile acid recycling

Detoxification

Metabolic functions

Liver has potential to regenerate

Some disease is reversible

Clinical signs

Hepatic dysfunction

Depression, decreased appetite and Lethargy

Stunting and weight loss

Vomiting and diarrhoea

Polyuria and polydipsia

Ascites and altered liver size

Increase = hepatomegaly

Decrease =microhepatica

Icterus = jaundice

Increased levels of bilirubin in blood

Bleeding tendency

Clinical biochemistry

Liver enzymes released into blood when liver is damaged

Cats and dogs

ALT

AST

Horses and ruminants

GGT

ALP/ALKP

Detection of levels of liver metabolites

Pre and Post -prandial bile acids

Cases of disease go up and stay up

Normally goes up then down

Serum bilirubin

Serum proteins

NB prandial = eating

Cholestasis

Intrahepatic

Decrease in secretion of bile by hepatocytes

Causes include infections

Decreased bile flow and back flow of biliary constituents

Impairs normal ???

Extrahepatic

?

Porto-Systemic shunts

Aberrent vessels

Connect portal circulation direct to caudal vena cava

Blood bypasses liver

2 principle types

Congenital ?

Acquired?

Clinical signs

Liver unable to detoxify waste products = hepatic encephalopathy

Hyper ammoniaemia

Depression / tremors

Head pressing

Polyuria/Polydipsia

Worse after eating

Diagnoses and treatment

Ultrasound , exploratory laparotomy , fluoroscopy

Prognosis

Aquired ??

Page 9

Metabolism

Introduction

Nutrients absorbed from SI and LI as glucose, amino acids / di-/tri-peptides, triglycerides, VFAs, FFAs, now must be used as energy or stored

Liver's role

Monosaccharides/ amino acids absorbed from gut pass through liver via hepatic portal vein

Lipids enter systemic circulation via lymphatic system , bypassing liver

Carnivores/Omnivores metabolism varies between 2 phases

Absorptive state

Eating

Energy derived from oxidation of absorbed nutrients

Post-absorptive state

Not eating

Energy derived from oxidation of stored nutrients

In herbivores nutrition almost continuous

No real distinction between absorptive and post-absorptive states

Absorptive state

Cells use absorbed nutrients as source of energy and for protein synthesis

Liver takes up glucose / amino acids , fills glycogen stores , synthesises lipids for export to other tissues

Excess CHO, fat and protein stored as lipids / glycogen

Net synthesis of protein in all cells

Carbohydrates (CHO)

Carnivores/ omnivores

CHO absorbed as monosaccharides, principally glucose

Galactose/ fructose converted to glucose in liver

Herbivores

CHO fermented to VFAs

Plasma glucose levels maintained at fairly constant level of 5mmol/l

In absorptive state glucose removed from blood and stored /metabolised

In post absorptive state glucose stores released

Fate of glucose

All tissues

Glucose used as energy source

Liver

Glucose taken up and stored as glycogen

This continues until glycogen represents 5% total liver mass

Glucose still remaining is converted to triglycerides

Some triglycerides stored in liver

Most exported to blood as VLDL

Skeletal muscle

Glucose taken up and stored as glycogen

Adipose tissue

Glucose taken up and converted to glycerol for synthesis of triglycerides

If glucose in excess in some is also converted to FFA

Lipids

Water insoluble therefore can't be transported in blood

Made water soluble by binding to proteins

FFA bound to albumin

All other lipids bound to apoproteins

Complex of lipids bound with apoprotein =lipoprotein

Apoproteins from interface between lipid core and aqueous blood thus enabling transport in blood

4 major types

Chylomicrons

Very low density lipoproteins (VLDL)

Low density lipoproteins (LDL)

High density lipoproteins (HDL)

NB Apoprotein - protein coat

Fate of lipids

Chylomicrons + VLDL

Converted to FFA by lipoprotein lipase

Taken up by adipose tissue or muscle

Chylomicron revenants + some VLDL remnants taken up by liver and metabolised

Remaining VLDL remnants converted to LDL and transfer cholesterol to other cells (Bad)

HDL

Transfers apoproteins to chylomicrons + VLDL to enhance lipid uptake

Removes cholesterol from other cells and transfers it to liver as cholesterol-rich HDL

Cholesterol-rich HDL degraded and releases cholesterol - converted to bile salts or excreted in bile

Seeimage?

Amino Acids

Liver keeps systemic level of amino acids constant

Most absorbed amino acids taken up by liver via hepatic portal vein

Used for protein synthesis

Converted to keto acids

Provide energy to liver cells

Converted to glucose/glycogen

Converted to fatty acids

Used to synthesise non-essential amino acids

Some bypasses liver and enters systemic circulation

Used for protein synthesis

Used for energy if glucose levels low

Converted to fat or glycogen for storage

Degradation of amino acids for energy leads to NH3

Converted true by lever and excreted by kidneys

EXCEPT herbivores

Urea transferred to fore stomach / LI via diffusion across epithelium or secreted in saliva

Used for microbial protein synthesis

Excess urea excreted by kidneys

Post-absorptive state

dependent on mobilisation of stored subsrates for energy

Liver maintains plasma glucose levels constant by

Mobilising glycogen stores

Glucoeogenesis

Use of glucose for energy reserved for brain, erythrocytes, kidneys

Under anaerobic conditions skeletal muscle also entirely dependent on glucose for energy

Other tissues derive energy from lipids (Glucose sparing)

In pregnancy / lactation glucose essential for foetal metabolism / lactose synthesis hence maintenance of plasma glucose levels in post-absorptive state especially important

Mobilisation of glycogen

During post-absorptive state no glucose being absorbed

Uptake of glucose by liver stopped

Other tissues continue to use glucose therefore plasma glucose declines

Liver response

Reducing its anabolic activities

Mobilising glycogen stores to release glucose into the blood

Glycogen stores relatively small

Gluconeogenesis

As glycogen stores depleted glucose synthesised from non-carbohydrate sources

Performed by liver and kidneys

Substrate is pyruvate

Formed from lactate, glycerol or amino acids

Many glycolysis enzymes also function in gluconeogenesis

Glucose concentration determines whether glucose converted to pyruvate or vice versa

All animals dependent on glucose but only omnivores absorb sufficient glucose directly from diet

Carnivores

Diet low in CHO therefor very dependant on gluconeogenesis from digested fat / protein

Herbivores

CHOs fermented to VFAs

Only propionic acid can serve as glucose pre-cursor in gluconeogenesis

During starvation glucose pre-cursor is amino acids from animals own skeletal muscle

Role of skeletal muscle

Glycogen stores in skeletal muscle similar to liver

In post absorptive state skeletal muscle also starts glycogenolysis

BUT can't dephoshorylate glucose phosphate hence free glucose can't be transported into blood stream

Instead glucose oxidised to pyruvate / lactate

Converted to glucose by liver and then can enter bloodstream

This cycling is referred to as the cori cycle

When skeletal muscle glycogen stores depleted amino acids from protein degradation serve as major pre-cursors for gluconeogenesis

Use of lipids as energy source

During absorptive state VLDL synthesised from excess glucose

During post-absorptive state VLDL synthesised from plasma FFA

FFA normally transported in blood bound to albumin

Amount of albumin. limits transport of FFA

FFA transport capacity increased by synthesis of VLDL

VLDL especially important in mobilisation of triglycerides from adipose tissue

Triglycerides broken down by hormone dependent lipase

Glycerol used in gluconeogenesis

FFA oxidised for energy production

Nervous tissue + fetuses have low uptake of FFA therefore heavily dependent on glucose for energy

Ketone Bodies

Mobilised FFA taken up by liver

Converted to Acetyl CoA and used as energy source by liver

Most acetyl CoA is surplus nd converted to ketone bodies

B-hydroxybutyrate <--> aceto-acetate -> acetone +CO2

Liver can't re-convert ketone bodies to acetyl CoA for energy production via citric acid cycle but some other issues can

Monogastrics

Ketone bodies synthesised exclusively by liver

Only low levels in pigs/ horses

Brain can switch to ketone bodies as energy source enabling mobilised proteins to last longer

Ruminants

Ketone bodies also synthesised from butyrate in ruminal epithelial cells

Very important as butyrate inhibits gluconeogenesis from pyruvate

Unable to limit brain glucose utilisation

Regulation of carbohydrate metabolism

Insulin

Increased uptake of glucose

Stimulates glycogenesis/ inhibits glycogenolysis

Increases use of glucose for ATP production

Inhibits gluconeogenesis

(Predominates in absorptive state)

Glucagon

Opposite effects to insulin

(Predominant in post-absorptive states)

Adrenaline

Stimulates glycogenolysis in liver

Maintains plasma glucose constant despite increased glucose consumption

Responsible for hyperglycaemia when stressed

(increased during exercise and stress)

Glucocorticoids

Permissive role in gluconeogenesis

(increased during starvation)

Regulation of protein and fat metabolism

Protein

Insulin (absorptive)

ANABOLYSIS

Increased amino acid uptake

Increased protein synthesis in liver and muscle

Glucagon (post-absorptive)

INCREASED amino acid uptake in liver only

Proteins degraded into amino acids that can be used gluconeogenesis

Fat

Insulin (absorptive)

Triglycerides synthesised from glycerophosphates / FFA and stored

Inhibition of FFA release into blood

Glucagon (post absorptive and during exercise )

Increases lipolysis in adipose tissue

Mobilisation of triglycerides for ATP production

Comparative Metabolism

Ratio of insulin:glucagon determines net effect

Absorptive state - ratio high

Post-Absorptive state - ratio

Ruminants require gluconeogenesis to occur in both absorptive and post absorptive state as primary source of energy is VFAs NOT glucose

Propionic acid / amino acids serve as pre-cursors for glucose in absorptive state

Amino acids / glycerol serve as pre-cursors for glucose in post absorptive state

Utililastion / production of glucose reduced

Proteins / lipids mobilised

Insulin: glucagon ratio remains relatively low and constant

Page 10

Equine GI tract

Functional anatomy

Ascending colon vastly modified into fermentation chamber

3 compartments separated by physiological valves

Caecum

Separated by caeca-colic valve

Ventral colon

Separated by narrow pelvic flexure

Dorsal colon

Separated from small colon by narrowing transverse colon

Transverse colon relatively short and narrows to meet descending colon

Longitudinal muscle not continuous strand but arranged into toenail bands

Diff number of taeniae in diff parts

Shorter than large intestine itself -- sacculations

Enable mixing

Delay transit time

Fermentation

Similar to that of ruminant fore stomach

Degree depends own material reading LI

Carnivores - most digestion and absorption already occurred therefore minimal

Ruminants/omnivores - moderate fermentation

Horses- vast majority of non-hydrolysable CHO reaches LI do extensive fermentation

Microbial prodcts are VFAs CH4 CO2

LI mucosa absorbs VFAs

Gasses passed to rectum by peristalsis and expelled

Microbial balance can be easily upset

As LI terminal part of GI some VFAs and all microbial protein tested and wasted

Rabbits and rat - coprophagy

Metabolism of VFAs

Energy source

???????????????

VFAs absorbed by SCFA/HCO3- exchanger

Na+ absorbed by Na channels and Na/H+ exchanger

Enhanced by aldosterone

????

Comparative physiology

Feral horse on grass based diet 75% energy derived from VFAs produced by microbial fermentation in hind-gut

Fermentation similar to that of ruminant fore stomach

Except SI occurs before fermentation

in ruminants hHCO immediately fermented so none passes into SI

In horse potentially lots of ?

Carbohydrate fermentation

???

Protein Fermentation

Hind gut more capable of absorbing animo acids/peptides

Less taken up by microbes

Good as microbial protein lost in faeces

Microbial N2 rwuirements satisfied by urea?

Water

More water reabsorption occurs in LI

At luminal pH most VFAs in ionic form - poorly absorbed

Local mechanism H+ secreted in exchange for Na+ converts ions to acid

HCO3_ secreted in????

VFA Absorption

Absorbed intact rather than metabolised once absorbed

In ruminants proportion of propionic acid increases with more HCO3- passing into LI

Substrate for amylolytic bacteria causing their proliferation

BUT hCHO mustn't be fed excessively?

??

Microbiology

Bacteria

Amylolytic population lower (Fermentation slower)

Protozoa

Diff species to ruminants

smaller number but larger

?

Fungi

Probably similar to ruminants

Foregut vs hindgut

Hindgut 70% as efficient

Microbes less efficient

Lower degree of amylolytic fermentation

Lose microbial protein

Coprophagy

Gut transit time??

Motility

LI transit time must be slow for fermentation

Foregut 24hr

Hindgut several days

Caecum and colon form continuous compartment

??

Caecal contraction

Segmental

Maintains high microbial activity for fermentation and absorption

Mass contractions

Contraction of entire caecum

Mass evacuation of caecal contents

?

Colonic

Segmental, Peristaltic and anti peristaltic

?

In horse

Antiperistaltic contractions occur distally

Slow movement of passage of chyme from ventral to dorsal via pelvic flexure

Ensure slow transit time

Omnivores/carnivores have mass movement fin colon for evacuation

Colic

Not a disease

Clinical sign of abdominal pain

True colic - GI pain

False colic - other abdominal organ pain

Results in highest levels of morbidity and mortality - accurate diagnosis is essential in order to treat

Most useful procedure in diagnosis is rectal examination

Caudal 3rd in reach

Rectal tear possible

Abdominal auscultation

Normal sounds

Every 3-5 mins

Left dorsal- SI/ small colon

Fluidy

Higher pitch

Left Ventral- pelvic flexure

Rightdorsal/vental- caecum

Loud

Sounds like toilet flushing

Abnormal sounds

Inc frequency

Usually mild pain

Enteritis

Spasmodic colic

Treated with muscle relaxers

Tympanitic

Usually quite painful

Gut distension with gas

Obstruction

Surgery needed

Dec frequency

Ileus

Obstruction

Rectal examination

Preferably in stocks

Spleen lying against left abdominal wall

Caudal pole of left kidney dorsal and left of midline

Nephro-splenic ligament

Caecum to right of midline

Ventral taenia extending from upper right to ventral midline

Aorta in dorsal midline

Root of the mesentery in dorsal mid-line running ventrally

Pelvic flexure lying left ventral

Small colon containing faecal pellets lying left dorsally

SI not usually directly palpable unless in contracts as you're palpating

SI obstruction

Requires surgery

Normally can't feel SI as empty

If distended by gas indicates obstruction

SI???

Ileal impaction

Firm tubular structure in centre of abdomen coursing towards caecum

If detected early by SI distilled??

Cecal Impaction

?

Colonic impaction

?

Left dorsal displacement

?

Right dorsal displacement

?

Large colon volvulus/torsion

Most dangerous (blood vessels involved)

Rapidly fata

?

Small colon impaction

?

Page 11

Histology

Layers of GI tract

Mucosa

Lamina epithelialis mucosae

?

Lamina propria mucosae

?

Lamina muscularis mucosae

>?

Submucosa

LCT

Muscularis

Inner circular

Outer longitudinal

Serosa

?

Oesophagus

Muco

Lam,epith =stratified squamous

Lam,propria = typical

Lam,musc = variable according to species

??

Stomach

Muco

Lamm epith contains gastric pits at bottom of which are glands

??

Lamprop conatins immune cells

Lammusc fairly extensive

Carnivores ----

?

Glandular secretions

Oesophageal region

Stratified squamous epithelium , non glandular

Cardiac and pyloric region

?

Fundic region

?

SI

Inc SA for absorption

?

Mucosa

Villi cell type s

?

Crypt cell types

?

Submuco musc sera = typical

?

Regions of SI

Duo

Extensive villi

Extensive submuco glands =

Jeju

Typical

Villi usually smaller and less dense

Ileum

Villi usually club shaped

Inc number of >??

LI

Villi absent

Crypts elongated

Lymph tissues extensive

Regions

Caecum

Colon

Rectum

Extensive goblet cells

Pancreas

2 function

Exocrine ?

Endocrine ?

Liver

Capsule of DCT which continues with inetersititail CT that divided liver parenchyma into functional units

Hepatic lobule

Central vein

Hepatic portal triads

Sinusoids lined by fenestrated Edith and hepatocytes ?

Ruminant stomach

?

Reticulum

Honey comb shape

?

Rumen

No muscularis mucosa

?

Omasum

?

Page 12

GI review

put on vital later

Think about

Species

Anatomy

Physiology

Pathophysiology

Anatomy

a) parietal peritoneum

b) parietal cavity

a) corony ligament - left and right

a) round ligament of the liver

b) umbilical vein

a) gall bladder

b) cystic duct

a) celiac , cranial and caudal mesentery

a)bladder??

b)??

a) Fundus, corpus, pylorus

b)?

a) 3- sigmoid flexure, cranial flexure, caudal flecure

a)horse

b) not v mobile, v small

a)duodenum

b)pancreas

a)jejunum 70-80%

b)meso-jejunum mesentery

a)greek greek latin

a) ileum

b) caecum

c) ileo-caecal fold

a)yes

b)small colon

a) fold

b)omentum

c)ligament

short answer Qs

Page 13

GI dilemmas

Terms

Mastication = Chewing

Digestion = Chemical breakdown by enzymes

Absorption = Selective movement of a molecule from one area to another

Excretion = Urination (Have been absorbed into blood stream before removal from body)

Egestion = Defecation (Never absorbed by body)

Regurgitation = Passive process

Vomiting = Active expulsion of (usually) toxins

Food

Protein, Carbohydrate (2 types) , Lipids

Hydrolysable carbs (alpha glucosidic bonds)

Non-hydrolysable carbs (beta glucosidic)

Energy, amino acids , gluconeogenesis

Carnivores , Omnivores, herbivore

Fore gut

Hindgut

Omnivore

Starch Digestion

Amylose (Maltose repeat units)

Hydrolysable carbohydrate

Amylase

Mouth, stomach (for a bit) and small intestine

pH more in middle

Fundus only secretes mucus in pigs

Horse Fundus lined with stratified squamous

Mouth=6.5 Stomach=2 SI=7.5

Acid

?

Stomach (Abomasum in ruminants)

??

?

?

Cardiac valve , Oblique angle oesophagus passing through diaphragm, Bicarb secreted from pancreas into duodenum, brunners glands, mucous, gastric pits

Ulcers , see upper and lower GI bleeds , Vomiting blood, Blood in faeces

Alkaline Tide - when food enters stomach acid secreted into stomach , bicarb goes into blood stream (then urine)

Yes pH tells us if theres presence of urine stone

?

Gastro-intestinal secretions

Pancreas, Liver, Gall bladder, Stomach, Salivary glands, SI, LI

Humans 10-12l

Dont absorb = dehydration, hypokalemic shock?

Humans L

???

Fibre digestion

Non-hydrolysable carbohydrates

Yes- by microbes

Fermentation chamber position depends on species

Fermentation

Yes Herbivores -- fore gut

Vomiting

?

?

?

?

Diarrhoea

Increased fluid contents of gut

Bacteria, decreased pH

?

Too much non-absorbable solute in gut draws water into gut

?

Blood in the faeces

??

?

?

Laminitic ponies

Inflammation of laminae

Hydrolysable carbohydrate

Spring

More hydrolysable carbs in grass then