GI Flashcards

1
Q

Composition of saliva

A

Dependent on diet + which glands are stimulated.
- Mucin
- Amylase (omnivores/horses NOT carnivores/ruminants)
- Bicarbonate (neutralisation/buffering)
- Phosphate (ruminants)
- Lysozyme/antibodies (reduce infection)
- Protein-binding tannins (leaf + bud eaters)
- Urea (ruminants

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2
Q

Salivary secretion in non-ruminants

A
  • primary secretion isotonic with blood
  • at low flow rates, secretion becomes hypotonic
  • at high flow rates secretion remains isotonic
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3
Q

Regulation of salivary secretion

A

Entirely under neural control
- Sympathetic - reduction in fight or flight
- Parasympathetic - increase during digestion

Basal salivary secretion for oral hygiene.

2 reflex pathways
- Congenital
- Conditioned

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4
Q

Congenital salivary reflex pathway

A

Initiated by taste/smell/presence of food in mouth
(in ruminants also by distension of orifices and rumination)

  • Afferent to salivary centre in brain
  • Efferent to salivary glands
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5
Q

Conditioned salivary reflex pathways

A

Pavlov dog experiments.
Initiated by repeated sensory stimuli associated with feeding
- Sight/smell of food
- Noise
Initiated in cerebral cortex and thence salivary centre in medulla oblongata

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6
Q

Motility

A
  • Segmental contractions - breakdown/mix
  • Peristaltic contractions
  • Anti-peristaltic contractions
  • Mass movement
  • Regulation of motility - chewing/initial swallowing/defaecation under voluntary control)
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7
Q

Chemical breakdown

A
  • Secretion of digestive juices
  • Salivary glands/liver/pancreas/glands in stomach + intestinal wall
  • Digestive juices extensively reabsorbed
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8
Q

Composition of digestive juices

A
  • Ions and pH appropriate for action of digestive enzymes
  • Mucus to lubricate food and protect mucosa
  • Enzymes to chemically breakdown food.
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9
Q

Enzymes involved in digestion

A

Carbohydrate:
- amylase, disaccharidases
(saliva/pancreas/intestinal mucosal surface)

Protein:
- pepsin/trypsin/peptidases
(stomach glands/pancreas/intestinal mucosal surface)

Fat:
- lipase, phospholipase
(pancreas/intestinal mucosal surface)

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10
Q

Absorption

A
  • Absorption is selective - most nutrients require specific transporter proteins
  • Active transport of nutrients
  • Directly by primary active transport
  • Indirectly by secondary active transport
  • Passive transport of nutrients
  • Facilitatively via transporter proteins
  • Diffusion down concentration gradient
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11
Q

Layers of the abdominal wall

A

Skin - can be tough in some species
- Variable cover in hair for insulation.

Subcutaneous fascia - superficial fascia
- Contains adipose (all over in pig, mainly inguinal area in others)
- Contains cutaneous trunk muscle (skin twitch)
Deep fascia (ox, horse)
- Developed into a tough fibro-elastic sheet = yellow abdominal tunic

Muscles

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12
Q

Muscles of the abdominal wall

A

4 muscles
Lateral (outside to inside):
- External abdominal oblique m.
- Internal abdominal oblique m.
- Transverse abdominal m.
Ventrally:
- Rectus abdominis

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13
Q

Functions of abdominal wall muscles

A

Encloses the abdominal cavity and its contents.
Motor functions:
- Contraction causes increase in intra-abdominal pressure
(used in vomiting, defaecation and micturition)
- If larynx is closed, also causes increase in intra-thoracic pressure (via diaphragm)
(used in breathing, coughing, sneezing)

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14
Q

Rectus abdominis m.

A
  • Straight abdominal muscle
  • 6 pack in humans
  • Originates on ventral surface of sternum/sternabrae
  • 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
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15
Q

External oblique abdominal m.

A
  • Outermost lateral abdominal wall muscle
  • Originates on lateral caudal surfaces of rubs 4+ and lumbodorsal fascia
  • Inserts on linea alba and prepubic tendon
  • Fibres run obliquely from cranio-dorsal to caudo-ventral
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16
Q

Internal oblique abdominal m.

A
  • Middle lateral abdominal wall muscle
  • Original on coral tuber and lumbodorsal fascia
  • Inserts on linea alba, last rib & cartilages of caudal ribs
  • Fibres run obliquely from caudo-dorsal to cranio-ventral
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17
Q

Transverse abdominal m.

A
  • Innermost lateral abdominal wall muscle
  • Originates on medial surfaces of ventral parts of caudal ribs and deep lumbodorsal fascia
  • Inserts on linea alba
  • Fibres run transversely
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18
Q

Sheath of Rectus Abdominis m.

A
  • Foremed from the tendons of the lateral abdominal wall muscles
  • They pass above/below rectus abdominis m. to join in the midline
  • This join is to referred to as “aponeurosis” and forms the linea alba
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19
Q

Innervation

A
  • Innervation by spinal nerves of last thoracic vertebra & L1-L5
  • Dorsal roots innervate dorsal musculature
  • Ventral roots split into 3 branches
    Medial - runs between TA + IAO down to RA
    Lateral - runs IAO + EAO down to midway
    Lateral cutaneous - perforates EAO to innervate skin
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20
Q

Inguinal canal

A
  • Internal oblique muscle has gap (=deep inguinal ring)
  • External oblique muscle has slit (=superficial inguinal ring)
  • Inguinal canal = potential space between these 2 slits
  • Significance of this will be covered in urogenital fortnight
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21
Q

Embryology of GI tract

A
  • Epithelium lining GI tract & associated exocrine gland = endoderm
  • Muscle & connective tissue = splanchnic mesoderm
  • As embryo develops part of yolk sac taken into body
    • This goes on to form the gut
    • Midgut separated from foregut/hindgut by cranial intestinal portals
    • Foregut/hindgut end blindly at oral/cloacal plates
  • Foregut differentiates into pharynx, oesophagus, stomach nd initial duodenum
  • Midgut differentiates into rest of duodenum, jejunum, ileum, caecum, ascending/transverse colon
  • Hindgut differentiates into descending colon and rectum
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22
Q

Peritoneum

A
  • Serous membrane that lines abdominal cavity & envelops abdominal organs
  • SIngle continuous sheet
    • Parietal peritoneum
      • Closely adherent to abdominal wall
      • Extends through inguinal canal
    • Visceral peritoneum
      • Closely adherent to abdominal canal
      • Envelops organs
    • Connecting peritoneum
      • Mesentary - connects bowel to body wall
      • Omentum - connects stomach to something
      • Fold - connects bowel to bowel
      • ligament - connects non-bowel to something
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23
Q

Topographical anatomy

A

The relationship of organs within the abdomen

Defined by the peritoneal attachments - to one-another or body wall

Aids or hinders surgical access - the peritoneum

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24
Q

Cavities

A

Abdominal cavity
- Defined by diaphragm cranially
- Abdominal wall laterally
- Contains all abdominal organs/structures including peritoneum

Peritoneal cavity
- The potential space between parietal & visceral peritoneum
- Contains nothing other than a small amount of peritoneal fluid - unless peritoneal inflammation = peritonitis

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25
Diaphragm
- Separates thorax from abdomen - Attaches to body wall at level of last rib - Extends into thorax to level of 5th inter-costal space - Aorta passes through aortic hiatus between left + right crura - Caudal vena cava passes through caval foramen in central tendon - Oesophagus passes through oesophagus hiatus
26
Connecting peritoneum
Mesentary - connects bowel to body wall Omentum - connects stomach to something Fold - connects bowel to bowel Ligament - connects non-bowel to something
27
Liver
4 lobes - L&R lobes (split into medial and lateral in dogs) - Caudate - Caudate process - Papillary process - Quadrate Peritoneal attachments: - Coronary ligament - R&L triangular ligaments - Falciform/round ligament Gallbladder - Cystic/hepatic/common bile ducts
28
Stomach
3 areas: - Fundus = blind ending - Corpus = body - Pylorus (pyloric antrum) Peritoneal attachments: - Greater omentum - Lesser omentum - hepato-gastric ligament - Gastro-splenic ligament
29
Spleen
- On LHS of abdomen - Blood reservoir - Abnormally enlarged in barbiturate euthanasia Peritoneal attachments: - Gastro-splenic ligament
30
Duodenum
- First part of small intestine - Exit of bile duct/pancreatic duct on major duodenal papilla - Exit of accessory duct on minor duodenal papilla Peritoneal attachments - Mesoduodenum - Duodeno-colic fold - Hepato-duodenal ligament (part of lesser omentum)
31
Jejunum
- Middle part of small intestine - Largest proportion of SI - Covered by greater omentum Peritoneal attachements: - Meso-jejunum/mesentary (fan shaped)
32
Ileum
- Terminal portion of SI - Enters into LI at caeco-colic junction Peritoneal attachments: - Ileo-caecal fold - Meso-ileum (extension of meso-jejunum)
33
Pancreas
2 lobes: - Right lobe running in cranio-caudal direction - Left lobe running media-laterally Peritoneal attachments: - Right lobe within meso-duodenum - Left lobe within deep leaf of greater omentum
34
Caecum
- First part of LI - Blind ending sac - In dog, ileum runs directly into colon, with caecum attached on side - In other species, caecum is continuous with colon and ileum enters LI at caeca-colic junction - NOT the appendix Peritoneal attachments: - Ileo-caecal fold - Caeca-colic fold
35
Colon
Ascending (right): - Right colic flexure - Transverse - passes cranial to root of mesentery Descending (left): - Left colic flexure - Rectum Peritoneal attachments: - Meso-colon to dorsal body wall
36
Enteric nervous system
- 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 (digestive juices/hormones)
37
Enteric nervous system 2
- Simple reflex arc; consists of a single motor neurone - Complex reflex arcs consist of simple reflex arcs connected by interneurons - nerve impulse is propagated wider. - Short reflex arcs enable GI tract to have extensive control of its activities - Most reflexes are stimulatory and cholinergic
38
Autonomic nervous system
Parasympathetic promotes digestion - Pre-ganglionic fibres run in vagus (cholinergic) - Post-ganglionic fibres embedded in wall of GI tract and connect to ENS (cholinergic) Sympathetic inhibits digestion - Pre-ganglionic fibres run in splanchic nerves (cholinergic) - Post-ganglionic fibres run along arteries to organ of innervation or in hypogastric nerves - Synapse with ENS to reduce Ach release at parasympathetic pre-synapses - Adrenergic to inhibit secretion + motility and decrease perfusion to GI tract
39
Autonomic Nervous System 2
- Connection to CNS (sight/smell/taste) - Entero-enteric reflexes - coordinate activity between different parts of GI tract
40
Phases of regulation
Cephalic phase: - Anticipation of food (Pavlov's) - Emotion - Coordinated by ANS Gastric phase: - Stomach distension/presence of peptides - Coordinated by ANS, ENS and hormones (mainly gastrin) Intestinal phase: - Intestinal distension/lumen contents - Coordinated by ANS, ENS and hormones
41
Regulation of Appetite
- Controlled by hypothalamus - Appetite centre (ventro-lateral hypothalamus) - has direct effect on animal's behaviour - Satiety centre (ventro-medial hypothalamus) - causes refusal of food, inhibits appetite centre 3 theories for mechanism of action: - Glucostat theory - regulated by levels of glucose - CCK theory - regulated by levels of CCK - Lipostat theory - regulated by levels of fat
42
Motility
Coordinated contraction of smooth muscle in GI tract 1) Segmental - Mixes lumen contents/breakdown (stomach) 2) Peristalsis - Moves intestinal contents in gradual aboral direction 3) Anti-peristalsis - Moves intestinal contents in oral digestion 4) Mass movement - Empties entire sections of GI tract
43
Pacemaker cells
Repetetive + spontaneous oscillations (~5/min) in membrane potential occur in groups of pacemaker cells (interstitial cells of Cajal) - Located between circular + longitudinal smooth muscle - Synchronisation of smooth muscle contractions achieved by transfer of oscillations to smooth muscle via gap junctions - If stimulus absent, 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 potentials determines strength of contraction.
44
Swallowing/deglutition
- Propulsion of food from oral cavity into oesophagus - Food mould into bolus by tongue and moved upwards and backwards to pharynx - under voluntary control - forces soft palette up to seal off nasal cavity - Pressure-sensitive sensory cells stimulated - swallowing centre in medulla initiates swallowing reflex - under involuntary control - Epiglottis closes off trachea - Complicated contraction/relaxation of muscles force food into oesophagus
45
Swallowing disorders
- Failure of soft palette to close off nasal cavity - Failure of epiglottis to close off trachea - Pharangeal paralysis - nerve/muscle injury - Botulism - clostridial toxins block Ach release - Myaestheania gravis - antibodies formed against Ach receptors - Anaestesia - may anapestics induce vomiting - swallowing process impaired - inhalational pneumonia
46
Anatomy of the oesophagus
Mucosal layer - Stratified squamous epithelium Submucosal layer Muscular layer - Inner circular/outer longitudinal - Composed of striated + smooth muscle Serial layer - Adventitia (loose connective tissue) only in neck - slower healing in surgery True serial layer in thorax
47
Innervation of the oesophagus
Sympathetic - via cervical sympathetic chain Parasympathetic - SVE/AA via recurrent laryngeal (cranial division of XI) to cranial cervical oesophagus - AE/AA via vagus to caudal cervical/thoracic oesophagus - species with striated muscle in caudal oesophagus still innervated by parasympathetic
48
Transport down oesophagus
Upper oesophageal sphincter closes behind food bolus (epiglottis opens to allow breathing) complicated peristaltic contractions force food down oesophagus - animals can swallow upwards Lower oesophageal sphincter opens to allow passage of food into stomach
49
Lower oesophageal sphincter
= Cardiac sphincter Physiological 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; reinforcing closure prevents regurgitation of acidic stomach contents
50
Vomiting/emesis
Active propulsion of stomach contents into oral cavity. - Deep inspiration with simultaneous closure of trachea/nasal cavity - increases intra-abdominal pressure via diaphragm Forceful contraction of abdominal muscles - NOT gastric muscles Cardiac sphincter opens Food propelled up oesophagus Upper oesophageal sphincter opens
51
Vomiting/emesis 2
- Controlled by vomiting centre in medulla - Stimulated by pharyngeal/gastric distension/irritation - Normal in dogs/cats to expel bones/hair - Ruminants prefer to regurgitate Horses/rats - Very well developed cardiac sphincter - Exaggerated oblique entry through diaphragm - Stomach usually ruptures before vomiting occurs
52
Gastric torsion
- Occurs in horses and wide-chested dogs - Stomach rotates 90-360° - Seals off cardiac sphincter; preventing vomiting - Stomach distends further with gas - If rotation compromises blood supply, gastric tissue becomes oedematous/hypoxic and necrotic - Stomach dilation can impair venous return to heart via caudal vena cava resulting in circulatory shock - Extreme emergency requires surgical intervention
53
Functional anatomy of simple stomach
Functions: - Digestion - Continuation of starch digestion - Initiation of protein digestion - Protection - Stomach acid kills bacteria ingested with food - Storage - Ensures food delivered to SI at controlled rate - Mechanical breakdown/mix - Breaks food + mixes with gastric juice to form a semi-liquid chyme Abomasum is ruminant equivalent of simple stomach
54
Embryological regions of the stomach
Oesophageal region: - Non-glandular - Stratified squamous epithelium Cardiac region: - Secretes mucous only Fundic region: - Secretes mucous/gastric juice Pyloric region: - Secretes mucous only - Regulates stomach emptying
55
Anatomical regions of the stomach
Cardia - entrance to stomach - Physiological valve Fundus - blind ending part of stomach Corpus - body of stomach Pylorus - exit from stomach
56
Cell types in stomach
Consist of cylindrical glands Mucous/goblet cells - Secrete mucous to protect against HCl Parietal/oxyntic cells - Secrete HCl to digest protein Chief/peptic cells - Secrete pepsinogen to digest protein Entero-endocrine cells - Secrete hormones
57
Motility of the stomach
Serves to: - Prepare stomach to receive a meal - Mix and mechanically break down chyme - Empty stomach contents to SI - Prevent regurgitation of stomach contents into oesophagus When an animal starts eating there is an initial relaxation of stomach smooth muscle to accommodate the meal - receptive relaxation - Regulated by swallowing centre via vagus - Transmitter = vasoactive intestinal peptide - NOT Ach
58
Motility of the stomach 2
- Mainly peristalsis - Start in fundus with weak contractions - Propagate down corpus - Pyloric sphincter opens to allow chyme into duodenum - When contractions reach pylorus, pyloric sphincter closes - Food forced back into corpus helps mixing
59
Regulation of stomach emptying
- Mainly regulated by strength of contraction - Also opening/closing of pyloric sphincter - Stimulation of emptying - Neural regulation - expansion of stomach walls increases strength of contraction - Hormonal regulation - release of gastrin increases strength of contraction and dilates pyloric sphincter - Inhibition of emptying - Factors in duodenum act to inhibit gastric contractions - increased pressure in walls - Low pH - High [fat/peptide] - High osmolarity - Neural regulation via increased sympathetic activity/decreased parasympathetic activity via vagus - Hormonal regulation via secretin, cholecystokinin & gastric inhibitory peptide (GIP)
60
Digestion in simple stomach
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 How can both of these enzymes function in the stomach?
61
Structure of starch
- Complex carbohydrate - A mixture of amylose and amylopectin - Basic unit is maltose - Amylose comprises double helix of maltose units linked by 1-4 ⍺-glycosidic bonds - Amylopectin comprises of branching chain of maltose units linked by 1-6 ⍺-glycosidic bonds Amylase can digest ⍺-glycosidic bonds but not β-glycosidic bonds found in cellulose
62
Starch digestion
- Initiated by salivary amylase in mouth - BUT food doesn't spend much time in mouth before it is swallowed - Newly swallowed food forced into centre of stomach - Acid secreted from stomach walls - Gradual decline in pH from centre of stomach to edge that allows starch digestion to continue
63
Comparative starch digestion
Omnivorous diets contain high levels of starch - Pigs have adapted stomachs to allow starch digestion to continue longer Herbivorous 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 Carnivorous diets contain low levels of starch - Carnivore saliva doesn't contain amylase (digest starch in SI)
64
Comparative salivary amylase levels
- High in pigs - Low in horses as diet usually contains low levels of starch - Absent in carnivores + ruminants - Very high in humans as stomach not adapted for starch digestion
65
Protein digestion
Gastric juice consists mainly of HCl + pepsinogen - Pepsin is inactive until it comes into contact with foreign protein as organs are made of protein Pepsinogen must be converted into pepsin before it can digest protein Stomach mucosa very resistant to digestion - Breach of mucosal barrier -ulceration
66
Functions of HCl
Convert inactive pepsinogen into its active form - pepsin Provides the required acidic environment for pepsin to digest protein Prevents fermentation by killing microbes - In pigs/horses some fermentation of starch into VFAs occurs as large part of stomach doesn't produce acid Degrades large chunks of connective + muscle tissue into smaller, more digestible parts
67
Secretion of HCl
Duration and volume depends on species - Max secretion occurs 2-3 hours after a meal in dogs cf pigs (almost continuous) HCl secreted by parietal/oxyntic cells Stomach pH reaches 2.0-2.5 Opposite process occurs in pancreas to neutralise pH of food passing into duodenum Urine pH increases just after a meal due to delay between food passing from stomach to pancreas
68
Secretion of pepsinogen
Synthesised + stored in chief/peptic cells Pepsinogen secreted in inactive form Activated by HCl in stomach Pepsin initiates degradation of protein and collagen by breaking peptide links adjacent to aromatic amino acids - These peptides stimulate further HCl secretion Pepsin can activate more pepsinogen - auto-catalysis
69
Stimulation of secretion
Reflex arcs - Long via vagus - Short locally 3 substances - Amplify eachother - Ach/histamine - Direct stimulation - Chief (pepsinogen. parietal (HCl) & mucin cells Gastrin - Almost entirely via stimulation of ECL cells to produce histamine - Mainly parietal cells (HCl)
70
Cephalic phase
Neural stimulation: - Before food has entered stomach - Caused by sight, smell, taste - Stimulates secretion - Directly via Ach - Indirectly via gastrin in blood
71
Gastric phase
Neural stimulation: - After food has entered stomach - Caused by - Stomach expansion - Peptides in lumen - Stimulate secretion - Directly via Ach - Indirectly via gastrin in blood
72
Intestinal Phase
After food has entered duodenum Stimulation or inhibition - Depends on acidity of chyme - Food components Stimulation via neural (cholinergic) + hormonal signals - CCK role varies according to species - Dogs = partial agonist (low H+) or strong antagonist (high H+) cats = strong agonist Most intestinal responses = inhibitory
73
Hormonal stimulation
- Mediated by gastrin - Mainly in response to peptides in stomach - Reaches target cells via blood - Maximal HCl secretion requires simultaneous by Ach, histamine and gastrin - Gastrin mediates its effect almost entirely via stimulation of ECL-cells to release histamine
74
Inhibition of secretion
Duodenal signals that inhibit stomach motility also inhibit gastric juice secretion - Hormonal via vagus - Hormonal Localised inhibition in stomach too - pH<2.0 stops gastrin release to protect gastric mucosa from damage - Before food enters stomach, H+ low but not buffered so gastrin inhibited - Once food enters stomach with buffers (mainly protein) H+ reduced so gastrin released again - More protein in diet --> more gastrin release
75
Gastric/duodenal ulceration
Stomach mucosa protected from HCl by: - Secretion of mucous layer - Epithelial CM and interconnecting tight junctions impermeable by H+ - Epithelial cells replaced every 2-3 days
76
Ulceration pathophysiology
Increased acid production (duodenal ulcers) Decreased protective functions (gastric ulcers) HCl + pepsin damage epithelial cells and underlying tissues = ulceration Damaged cells produce histamine which stimulates acid secretion and intensifies problem Diarrhoea due to increased secretion + decreased absorption (villi damaged by acid) Faeces appear dark red/black
77
Ulceration Aetology
- H Pylori in humans - NSAIDs - inhibit prostaglandin synthesis (prostaglandins stimulate production of mucous and bicarbonate) - Protective mechanisms reduced - Mast cell tumours/leukaemia - Produce XS histamine - Increases HCl production - Gastrin-producing tumours - Produce XS gastrin - Increases HCl production
78
Ulcer treatment
Aimed at reducing HCl secretion - Anti-histamines - Proton Pump Inhibitors Protecting ulcerated mucosa - Antacids - Mucosal Binding Agents
79
Digestion + Absorption (intestines)
SI is major site of digestion + absorption in simple stomached mammals Absorption is selective process occurring via specific transporter proteins by - Diffusion down conc gradient - Secondary active transport Most organic nutrients + monovalent ions absorbed irrespective of body requirements Divalent ions + trace elements absorbed depending on body requirements SI has large reserve capacity - Up to 50% can be resected without hindering digestion/absorption Most nutrients absorbed along entire length of SI 2 phases of digestion - Luminal - enzymes secreted by salivary glands/pancreas - Membranous - enzymes attached to epithelial surface of intestinal cells Anything remaining undigested by SI passes on to LI for microbial fermentation
80
Functional anatomy of SI
3 parts - Duodenum - 15% of length - Jejunum - 75% of length - Ileum - 10% of length Standard intestinal structure - Mucosa - Submucosa - Muscle (inner circular/outer longitudinal) - Serosa Surface area massively increased for absorption by: - Mucosal folds - Villi - Microvilli
81
Cell types (intestine)
4 types of intestinal epithelial cell - Goblet cells secrete mucous for lubrication + protection of mucosa and bicarbonate for neutralisation of stomach acid - Enteroendocrine cells control digestive function via sensory mechanisms and release of hormones - Paneth cells possibly involved in defence against microbial penetration - Enterocytes (majority of cells) responsible for absorption via transporter proteins - contain many brush border digestive enzymes - enzymes remain attached to epithelial membrane Continuous turnover of cells with migration from crypts up villus - Sloughed off at villus tip - Migration takes 2-5 days
82
Motility of SI
Serves to: - Mix luminal contents - Segmental contractions (digestive period) - Propel contents down SI at appropriate rate to allow max digestion + absorption - Peristaltic contractions (inter-digestive period) SI emptying - Circular muscle at ileo-caecal junction well developed - Functions as physiological valve/sphincter - 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 to colon - Gastro-ileal reflex
83
Segmental contractions
CIrcular contractions occur along distended intestine - Divide intestinal contents into small segments - New contractions occur in centre of distended segment - Repeated many times - Mixes contents with digestive juices - Moves contents towards mucosal surface for digestion/absorption
84
Segmental contractions 2
Main type of contraction during digestive period - Intense contractions upon emptying of stomach - Short periods of weak segmental contractions - allows weak peristaltic contractions to occur - BUT they soon die out - Overall a slow aboral movement of chyme occurs - As chyme reaches distal SI, feedback mechanism inhibits proximal contractions - Mediated via neural/hormonal mechanisms - major mechanism for coordinating SI transit to allow maximal digestion/absorption - SI transit ~3-4 hours in most species regardless of size
85
Peristaltic contractions
Main type of contraction when digestion/absorption complete (inter-digestive period) - Irregular moderate peristaltic activity - Propagates a short distance - Regular strong peristaltic activity - Propagates a long distance - Each new contraction starts slightly further down the SI - When a peristaltic contraction reaches ileum, a new one starts in duodenum - Migrating Myo-electric complex - Takes ~1-2 hours to propagate down entire SI - Empty SI of contents - Prevent retrograde flow from colon - Peristalsis can occur in reverse but reverse contractions die out quickly in SI
86
Propagation of peristalsis
Most motor neurone of ENS release Ach - Stimulates smooth muscle contraction Some inhibitory transmitters released too Distension of segment causes stimulation + inhibition - Longitudinal muscle relaxes/circular muscle contracts behind chyme - Longitudinal muscle contracts/circular muscle relaxes in front of chyme
87
Regulation of motility (intestine)
Controlled by interstitial cells of Cajal = pacemaker cells Spontaneous oscillations always present - Independent of neuronal/hormonal influences - Highest frequency of slow waves in duodenum declining towards ileum - Duodenum can inhibit stomach emptying if chyme causes too much distension - If sufficiently depolarised, multiple action potential spikes occur, causing smooth muscle contraction - Propagate from cell-cell via gap junctions - Strength of contraction determined by number of action potential spikes occurring
88
Regulation of motility (intestines) 2
Mainly regulated by ENS 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 coordinate motility in different parts of the GI tract via long reflex arcs
89
Carbohydrate digestion + absorption (intestines)
Provide most of energy in herbivores/omnivores - Polysaccharides - ⍺-glycosidic bonds - digestible by mammalian enzymes - β-glycosidic bonds - requires microbial fermentation - Disaccharides - Maltose - Sucrose - Lactose - Monosaccharides
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Carbohydrate digestion
Only monosaccharides can be absorbed - Luminal digestive phase: - Starch/amylose --> maltose - Salivary amylase continues digestion in SI with pancreatic amylase - Membranous digestive phase - Maltose --> glucose x2 - Sucrose --> glucose + fructose - Lactose --> glucose + galactose
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Disaccharidases
Disaccharidases attached to enterocyte brush border - Maltase/Sucrase/Lactase - Digestion of maltose/sucrose very quick - rate of absorption is limiting factor - Lactose digestion is much slower - absorption rate is limiting factor - Disaccharidase levels change with age - Neonate - high lactase/low maltase - Adult - low lactase/high maltase - Ruminants - no sucrase
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Carbohydrate absorption
Glucose and galactose absorbed by sodium glucose co-transporter (SGLT1) - Secondary active transport - Na+ & glucose bind to transporter on luminal side - Conformational change in transporter moves Na+ & glucose/galactose 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 gradient into blood via facilitative transporter GLU2 Fructose absorbed down concentration gradient by facilitative transporter (GLUT5) - Passive transport - Diffuse out of cytosol down concentration gradient into blood via GLUT2 Transferred to liver via hepatic portal vein Stored as glycogen or continue in circulation to be metabolised for energy
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Secondary active transport
Na+ moves from lumen into enterocyte down its concentration 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 2 K+ ions - Maintains net -ve charge in cell Requires ATP (primary active transport)
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Adaptation to diet (intestines)
Some digestive/absorptive functions regulated by diet Others are pre-programmed to appear at a certain phase of life and then disappear irrespective of diet Omnivores: - Diet contains high levels of bicarbonate - SGLT1 levels remain high - Expressed high throughout SI Ruminants - SGLT1 expression in lambs is high - As rumen develops, less bicarbonate passes into SI - SGLT1 expression declines to negligible amounts in adult grazers - Maintained in intermediates/browsers as some bicarbonate bypasses fermentation and passes into SI Horses - SGLT1 highest proximally declining distally in wild horses on grass - To compete, domestic horses fed increased levels of bicarbonate - Consequently SI adapts by increasing levels of SGLT1 overall but especially proximally
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Lactose intolerance
Main carbohydrate in milk is lactose Requires lactase to digest 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 force -> decreased water absorption (diarrhoea) - Once reaches LI 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 in pain/discomfort
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Protein digestion + absorption
Carnivorous/omnivorous diets high in protein Herbivorous diets low in protein - BUT ruminant SI receives lots of protein in the form of microbial protein passing from rumen Protein digestion initiated in the stomach Continues in SI with pancreatic proteases (luminal phase of digestion) End products of digestion are di/tri-peptides and amino acids - Most protein absorbed as di/tri-peptides - Amino acids transported into enterocytes via Na+ co-transport similar to monosaccharides (secondary active transport) - Di/tri-peptides 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.
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Protein digestion in neonates
Proteins can't be absorbed as they would be regarded as foreign material and evoke an immune reaction In neonates, the immune system is poorly developed Placental transfer of maternal antibodies occurs via colostrum in the 1st 24-36 hours of life To enable absorption of intact protein - Epithelial cells of intestine are permeable to intact protein - Stomach products negligible amounts of HCl - Pancreatic enzyme secretion is low - Colostrum contains trypsin inhibitors Consequently large amount of maternal antibody can absorbed in the 1st 24 hours to provide passive immunity to the neonate
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Functional anatomy of the pancreas
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 (islets of Langerhans) 2 major functions - digestion (exocrine pancreas) - regulation of metabolism (endocrine pancreas)
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Exocrine pancreas
Principal function is digestion Pancreatic juice has 2 major components - bicarbonate to neutralise stomach acid thereby protecting SI mucosa - also provide the correct pH for digestive enzymes - Enzymes to digest food material for absorption in SI - Involved in carbohydrate/protein/fat 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
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Ionic composition of pancreatic juice
Similar to blood. HCO3- actively transported into duct lumen in exchange for chloride - Water follows by osmosis - H+ transported into bloodstream - negates alkaline tide - At normal flow rates, HCO3- reabsorbed into acing cells - At high flow rates (during digestion) not enough time for reabsorption so pancreatic juice remains highly alkaline - Na+/K+ composition constant whatever the flow rate
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Enzymatic composition of pancreatic juice
Secretion of digestive enzymes for carbohydrate/fat/protein breakdown - Proteases secreted in inactive form to prevent auto-digestion - Amylase breaks down starch (continues where salivary amylase left off) - Lipases/phospholipases breakdown fat to glycerol/fatty acids
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Activation of enzymes
Pancreatic juice contains trypsinogen/inactive proteases Duodenal epithelial surface contains enteropeptidase - Trypsinogen --> trypsin Trypsin auto-catalyses itself as well as activating other proteases As a precaution, pancreatic cells produce trypsin inhibitor to prevent auto-digestion
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Regulation of secretion (pancreas)
3 phases to digestion - Cephalic phase - Gastric phase - Intestinal phase All phases increase pancreatic juice secretion Cephalic/gastric mediated by vagus/gastrin - Carnivores - only enzymatic component - Horse/pig - ionic component as well (for LI fermentation) Intestinal phase mediated by secretin/CCK - Causes largest increase in secretion - Vasoactive inhibitory peptide inhibits effect of secretin
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Secretin
- Released from duodenum in response to H+ - Increases HCO3- secretion - Negative feedback mechanism - As acid chyme gradually neutralised stimulus for secretin release diminishes
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Cholecystokinin (CCK)
Released from duodenum in response to fat/protein metabolites Increases enzyme secretion Also causes gall bladder to contract Positive feedback mechanism - Increased enzyme secretion produce more metabolites which in turn stimulate further CCK release
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Comparative physiology (pancreas)
Differences due to pattern of eating Ruminants - Continuous flow of rumen contents into abomasum/SI - pancreatic juice secretion continuous irrespective of eating Carnivores/omnivores - Intermittent flow of stomach contents into SI - pancreatic juice secretion intermittent Horses - Continuous flow of stomach contents into SI - pancreatic juice secretion continuous - BUT also increases after feeding cf ruminants - Horse pancreatic juice low in HCO3- - able to neutralise acidic stomach components due to copious secretion of HCO3- by ileum
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Endocrine pancreas
Principle function is regulated of metabolism Clusters of cells scattered throughout the pancreatic tissue = islets of Langerhans - 1-2% of pancreatic mass - 3 major types of cell β~65% ⍺~25% δ~10% Hormones - Insulin - produced by β-cells - Glucagon - produced by ⍺-cells - Somatostatin - produced by δ-cells - paracrine effect to inhibit both insulin + glucagon secretion Secreted in bloodstream and passes to liver via hepatic portal vein prior to circulating to other tissues
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Insulin
Peptide hormone released in response to increased plasma levels of glucose + amino acids Overall anabolic effect Produced in pancreatic β-cells - Synthesised as pre-pro-hormone - Converted to pro-insulin - Inactive due to c-peptide - Secreted as active insulin by cleavage of the C-peptide - Plasma half life of 5-8 mins - Deactivated in liver by cleavage of di-sulphide bonds
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Regulation of insulin
Stimulated by increase in plasma glucose Also by increase in plasma amino acids Direct feedback mechanism independent of other factors Bi-phasic secretion - Initial immediate secretion of stored insulin lasting 5-15 mins - Followed by more prolonged secretion of newly synthesised insulin adjusted to plasma levels of glucose Also stimulated by GI hormones released when food enters duodenum Thus insulin secreted in anticipation of increased absorption of glucose/amino acids - Insulin secretion greater when glucose administered orally cf intra-venously
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ANS regulation of insulin
Parasympathetic activity via vagus increases insulin secretion - Part of long-reflex arc - Amplifies hormonally-regulated secretion Sympathetic activity + adrenaline releases decreases insulin secretion
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Actions of insulin
Binds to receptors on target cells - Receptor functions as a tyrosine kinase upon activation - Phosphorylation of intra-cellular proteins mediates different actions of insulin Stimulates cell uptake of nutrients during absorptive phase Most important anabolic mediator Glucose uptake enhanced by mobilisation of glucose transporter (GLUT4) to cell membranes - Nearly all tissues (esp skeletal muscle/adipose tissue) - Brain, liver, intestines, kidney + mammary tissue insulin-independent - Glucose uptake mediated by different GLUT transporters
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Actions of insulin 2
Amino acid uptake enhanced by amino-acid transporter proteins - Nearly all tissues - Increases intra-cellular amino acids for energy + protein synthesis (anabolic effect) Increases concentration/activity of intra-cellular enzymes involved in metabolism of glucose/amino acids/lipids - Especially in liver, skeletal muscle, adipose tissue - Increases glycogenesis in liver/FFA for tri-glyceride synthesis - Inhibits enzymes that breakdown try-glycerides
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Diabetes Mellitus
Plasma glucose elevated (hyperglycaemia) due to decreased uptake by cells Capacity for kidneys to re-absorb glucose exceeded (glycosuria) Fairly rare but occurs most often in carnivores/omnivores 2 types - Type I - insulin-dependent - Insulin production impaired - Treated by insulin injections - Type II - non-insulin dependent - Cells resistant to insulins effects IDDM most common - Caused by pancreatic inflammation, hyper-secretion of hormones antagonistic to insulin
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Diabetes 2
Hyperglycaemia - polydipsia/polyuria - Would expect urine specific gravity to be low but artificially normal/high due to glucosuria Degradation of lipids increases leading to increased 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 Hypoglycaemia - Plasma glucose below normal physiological range - Most often caused by insulin overdose - also insulinoma - Treated by oral/IV glucose - Ruminants less sensitive to hypoglycaemia
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Glucagon
Peptide hormone released in response to decreased levels of glucose + amino acids Overall catabolic effect Produced in pancreatic ⍺-cells - Synthesised as pre-pro-hormone - Converted to pro-glucagon - Plasma half-life of 5-6 mins - Deactivated by metabolism in liver/kidneys
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Regulation/actions of glucagon
Stimulated by decrease in plasma glucose - Also by increase in plasma amino acids + increased sympathetic activity Binds to receptors on target cells - activates adenyl cyclase Actions are reverse of insulin - Net effect on metabolism depends on ratio of insulin: glucagon Increases plasma glucose by stimulating liver glycogenolysis and gluconeogenesis Little effect on any tissues other than liver
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Gross anatomy of liver
Located in the dome of the diaphragm within the abdominal cavity Basic liver has 4 lobes - Left, quadrate, right % caudate - In dog, cat, pig, left&right lobes split into medial and lateral parts - Caudate lobe has 2 parts - caudate + papillary processes Gallbladder - Present in carnivores, ruminants, pigs, mice - Absent in horses, rats.
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Liver histology
Liver surrounded by capsule of connective tissue Capsule extends into liver as septae - highly branched Septae delineate the structural units of the liver = hepatic lobule
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Hepatocytes
Chief functional cells of liver Absorb molecules from "space of disse" - absorption occurs across sinusoidal membrane Bile canaliculus is dilated intercellular space between cells - bile secreted across canalicular membrane
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Biliary system
Conveys bile from to duodenal lumen Secrete bile across hepatocyte membrane into canaliculi Bile flows from canaliculi into small bile ducts = ductules Ductules anastomose into larger ducts Ducts coalesce to form hepatic bile ducts Hepatic bile ducts lead into common bile duct Common bile duct enters duodenum at Sphincter of Oddi If present, bile moves between gallbladder & bile duct via cystic duct
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Blood supply of liver
Hepatic portal vein - 75% of blood entering liver Hepatic artery - 25% of blood entering liver Sinusoids - Venous + arterial blood mix as they flow into sinusoids 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
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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
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Hepatic Acinus
= Functional unit of liver Can be divided into zones Zones correspond to distance from arterial blood supply Cells in zone 1 (nearest to artery) best oxygen supply Cells in zone 3 (furthest from artery) poorest oxygen supply
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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/artery through sinusoids towards central vein
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Functions of the liver
Detox of body wastes, xenobiotics and drugs Synthesis of cholesterol + bile acids Synthesis of plasma proteins Breakdown of RBC (degradation of haem) Carbohydrate, lipid + amino acid metabolism Removal of bacteria Production of clotting factors Storage of glycogen, iron, copper and vitamins
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Liver metabolism
Carbohydrate metabolism - Glycogenesis - Glycogenolysis - Gluconeogenesis Lipid metabolism - Oxidation of fatty acids + ketone body formation - Synthesis of cholesterol, phospholipids & bile acids Protein metabolism - Deamination + transamination of amino acids - Synthesis of non-essential amino acids
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Detoxification + clearance (liver)
Major role in purification, transformation and clearance - All 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 contain non-specific enzyme cytochrome P450 followed by further degradation - Conjugated with water-soluble compounds and excreted in bile
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Detoxification and clearance 2 (liver)
Drugs (pharmaceuticals) - Nearly all drugs are modified/degraded in liver - Conjugated or modified for excretion in urine or bile Toxins - Responsible for detoxifying chemical agents + poisons - Acute/chronic poisoning Endogenous Metabolites - Ammonia converted to urea + excreted in urine - Hormones inactive by liver - Haem broken down into bilirubin and excreted in bile
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Examples of Plant toxins
Digitalis - From digitalis purpurea (floxglove) - Cardiac glycoside Aflatoxin - From aspergillus fungus growth on damp grain/soybeans Phylloerthrin - Metabolite of chlorophyll - Causes photosensitzation in sheep
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Degradation of Red blood cells
RBCs removed from blood by macrophages in spleen + liver Degraded to yield haem from haemoglobin Haem converted to bile pigments - Haem converted to biliverdin (green) in macrophage - Biliverdin transformed to bilirubin (yellow) - Bilirubin transported to liver in blood bound to albumin - Bilirubin conjugated with glucoronic acid in liver
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Excretion of bile pigments
Bile pigments play no part in digestion = waste route to haem Conjugated bilirubin excreted into bile In gut bilirubin can be acted on by intestinal bacteria - Remove glucoronic acid - Metabolise to stercobilin (brown) - This is what gives faeces its colour
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Functions of bile
Promotes hydrolysis by lipases (effective detergent) - Bile acids facilitate digestion of dietary triglycerides by acting as emulsifying agents - render fats accessible to pancreatic lipases Facilitates intestinal absorption of lipids - Bile acid micelles improve solubilisation and uptake of lipids Exit route for waste products and drugs - Synthesis and subsequent excretion in the faeces and represents only significant mechanisms for the elimination of XS cholesterol
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Composition of bile
- Water - Electrolytes - bicarbonate actively secreted into bile - Biliary proteins - Bile pigments - Cholesterol - Phospholipids - Bile acids - Cholic acid - Chenodeoxycholic acid
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Storage of bile
Bile stored in gallbladder Allows storage + concentration of bile Beneficial to animals with intermittent digestion: - Carnivores - Omnivores Herbivores with continuous digestion: - Levels of fat in diet usually low - Horses - lack gallbladder - Ruminants - have gallbladder with ineffective concentrating mechanism - due to presence of fermentation chamber occurring before duodenum probably intermittent rather than continuous
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Conjugation of bile acids
2 major bile acids synthesised from cholesterol in liver - Cholic acid - Chenodeoxycholic acid These bile acids are hydrophobic To make them water soluble they are conjugated with glycine/taurine - Cholic acid + glycine = glycocholic acid - Cholic acid + taurine = Taurocholic acid - Chenodeoxycholic acid + glycine = Glycochenodeoxycholic acid - Chenodeoxycholic acid + Taurine = Taurochenodeoxycholic acid
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Secondary Bile Acids
Following participation in lipid digestion/absorption primary bile acids move into ileum In terminal ileum some primary bile acids can be modified by bacteria Deconjugated and converted into secondary bile acids - Cholic acid -> deoxycholic acid - Chenodeoxycholic acid -> lithocholic acid
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Summary of bile acids
Primary bile (synthesised in liver) - Glycocholic acid - Taurocholic acid - Glycochenodeoxycholic acid - Taurochenodeoxycholic acid Secondary bile acids (metabolisation of primary bile acids by bacteria) - Lithocholic acid - Deoxycholic acid
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Bile acid secretion
Bile acids transported into bile canaliculus - This is an active process - Performed by bile acid transporter protein ATP-driven bile excretory pump (BSEP) Bile canaliculi isolated from hepatocyte cell membrane by tight junctions to prevent leaks Bile canaliculi feed into large canals Bile emptied into duodenum at major duodenal papilla - Controlled by circular collection of smooth muscle (sphincter of Oddi) Bile salts not fat soluble so remain in SI lumen until actively reabsorbed in ileum
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Enterohepatic circulation
Bile acids absorbed from terminal ileum by active transport Transport back to liver via hepatic portal vein Efficiently captured from blood stream by liver via Na+ dependent Taurocholate co-transport polypeptide (NTCP) This recycling process referred to enterohepatic circulation
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Regulation of Bile secretion
Parasympathetic Sytem (vagus) CCK - Released in response to presence of fat in duodenum - Causes contraction of gall bladder + relaxation of sphincter of Oddi - Animal without gallbladder have inactive sphincter of Oddi with continuous flow of bile into duodenum Secretin - Released in response of acid chyme in duodenum - Mainly stimulates release of pancreatic juice - But also increase HCO3- production by liver
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Regulation of bile secretion
Also regulation by amount of bile salts returning to liver via enterohepatic circulation During a meal, presence of fat in duodenum causes release of CCK - Contraction of gallbladder - Relaxation of Sphincter of Oddi - Enterohepatic circulation of bile salts increases - Consequent increase in bile secretion by liver Between meals lack of fat in duodenum - Relaxation of gallbladder - Contraction of Sphincter of Oddi - Enterohepatic circulation of bile salts decreases - Bile stored and concentrated in gallbladder
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Hepatic dysfunction + disease
Numerous causes of liver disease in animals - Infection - Poisoning (acute/chronic) - 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
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Clinical signs of liver disease
- Hepatic dysfunction - Depression, low appetite - Lethargy - Stunting + weightloss - Vomiting + diarrhoea - Polyuria/polydipsia - Ascites + altered liver size - hepatomegaly - microhepatica - Icterus = jaundice - Increased bilirubin in blood - Bleeding tendancy
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Clinical biochemistry
Liver enzymes released into blood when liver is damaged - Cats/dogs - Alanine aminotransferase - Aspartate aminotransferase - Horses/ruminants - Gamma glutamyl transferase - Alkaline phosphatase Detection of levels of liver metabolites - Pre/post-parandial bile acids - Serum bilirubin - Serum proteins
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Cholestasis
Intrahepatic - Decrease in secretion of bile by hepatocytes - Causes include infections - Decreased bile flow and back flow of biliary consituents - Impairs normal biochemical processes within hepatocytes Extrahepatic - Obstruction of gallbladder and/or bile ducts - Causes include tumour, gallstones or inflammation of gallbladder - Major clinical sign = jaundice
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Porto-systemic shunts
- Aberrant vessels - Connect portal circulation to caudal vena cava - Blood bypasses liver - 2 main types - Congenital = single shunt - Acquired = multiple shunts due to portal hypertension
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Porto-systemic shunts: clinical signs
Liver unable to detoxify waste products = hepatic encephaly - Hyperammoniaemia - Depression/tremors - Head pressing Polyuria/polydipsia Worse after eating
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Porto-systemic shunts: diagnosis + treatment
Ultrasound, ex lap, fluroscopy Prognosis: - Acquired = poor - Congenital can be corrected by surgery
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Absorptive State (metabolism)
Cells use absorbed nutrients as source of energy + for protein synthesis Liver takes up glucose/amino acids, fills glycogen stores, synthesises lipids for export to other tissues XS CHO, fat + protein stored as lipids/glycogen Net synthesis of protein in all cells
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Carbohydrate
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 5 mmol/l - In absorptive state, glucose removed from blood + stored + metabolised - In post-absorptive state stores released
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Fate of glucose
All tissues - Glucose used as energy source Liver - Glucose taken up/stored as glycogen - This continues until glycogen represents ~5% total liver mass - Remaining glucose converted into triglycerides - some stored in liver - most exported to blood as VLDL Skeletal muscle - Glucose taken up/stored as glycogen Adipose tissue - Glucose taken up + converted to glycerol for synthesis of triglycerides - If glucose in XS converted to FFA
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Lipids
Water insoluble so can't be transported in blood Made water soluble by binding to proteins - FFA bound to albumin - All other lipids bound to apoproteins - To form lipoprotein - Apoproteins form interface between lipid core + aqueous blood (similar to bile acids) enabling transport in blood - 4 major types: - Chylomicrons - VLDL - LDL - HDL
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Fate of lipids
Chylomicrons + VLDL - Converted to FFA by lipoprotein lipase - Taken up by adipose tissue or muscle - Chylomicron remnants + some VLDL remnants taken up by liver + metabolised - Remaining VLDL converted to LDL + transfer cholesterol to other cells (bad cholesterol) HDL (synthesised in liver) - Transfers apoproteins to chylomicrons + VLDL to enhance lipid uptake - Remove cholesterol from other cells + transfers it to liver (good cholesterol) as cholesterol-rich HDL - Cholesterol-rich HDL degraded + releases cholesterol - converted to bile salts or excreted in bile
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Amino Acids
Liver keeps systemic level of amino acids constant Most (75%) absorbed amino acids taken up by liver via hepatic portal vein - Used for protein synthesis - Albumin, fibrinogen, enzymes - 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 (25%) bypasses liver + enters systemic circulation - Used for protein synthesis - Used for energy if glucose for storage Degradation of amino acids for energy leads to NH3 - Converted to urea by liver + excreted by kidneys - EXCEPT herbivores - Urea transferred to forestomach/LI via diffusion across epithelium or secreted in saliva (ruminants only) - Used for microbial protein synthesis - XS urea excreted by kidneys
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Post absorptive state (metabolism)
Dependant on mobilisation of stored substrates for energy Liver maintains plasma glucose levels constant by: - Mobilising glycogen stores - Producing glucose from other sources (gluconeogenesis) 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
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Mobilisation of glycogen
During post-absorptive state no glucose being absorbed Uptake of glucose by liver stopped Other tissues continue to use glucose so plasma glucose declines Liver responds by: - Reducing its anabolic activities - Mobilising glycogen stores to release glucose into the blood Glycogen stores relatively small - Only sufficient to maintain plasma glucose levels for a few hours
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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 gluconeogeneis 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 so dependant on gluconeogenesis from digested fat/protein Herbivores - CHOs fermented to VFAs - Only propionic acid can serve as glucose pre-cursor in gluconeogensis During starvation, glucose pre-cursor is amino acids form animal's own skeletal muscle
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Role of skeletal muscle
Glycogen stores in skeletal muscle similar to muscle In post absorptive state skeletal muscle also starts glycogenolysis - BUT can't dephosphorylate GP ; free glucose can't be transported into bloodstream - Instead glucose oxidised to pyruvate/lactate - Converted to glucose by liver and can enter bloodstream - Referred to as Cori cycle When skeletal muscle glycogen stores depleted amino acids from protein degradation serve as major pre-cursors for gluconeogenesis
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Use of lipids as energy source
During absorptive state VLDL synthesised form XS 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-dependant lipase - Glycerol used in gluconeogenesis - FFA oxidised for energy production (glucose sparing) - Nervous tissue + foetuses have very low uptake of FFA so heavily dependant on glucose for energy
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Ketone Bodies
Much mobilised FFA taken up by liver Converted to Acetyl CoA and used as energy source by liver Most acetyl CoA is surplus + converted to ketone bodies - β-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 tissues can Monogastric animals: - Ketone bodies synthesised in pigs/horses (most FFAs re-esterified to triglycerides) - 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 - important as butyrate inhibits gluconeogenesis from pyruvate - Unable to limit brain glucose utilisation
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Regulation of carbohydrate metabolism
Insulin (predominates in absorptive state) - Increased uptake of glucose - Stimulates glycogenesis - Inhibits glycogenolysis - Increases use of glucose for ATP production - Inhibits glujconeogeneis Glucaogn (predominates in post-absorptive state) - Opposite effects to insulin Adrenaline - Stimulates glycogenolysis in liver - Maintains plasma glucose constant despite increased glucose consumption - Responsible for hyperglycaemia when stressed Glucocortosoids (^ during starvation) - Permissive role in gluconegenesis
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Regulation of protein metabolism
Insulin (absorptive state) - Increased amino acid uptake - Increased protein synthesis in liver and muscle (anabolysis) Glucagon (post-absorptive state) - Increased amino acid uptake in liver only - Proteins degraded to amino acids that can be used in glucogneogeneis
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Regulation of fat metabolism
Insulin (absorptive state) - Triglycerides synthesised from glycerophosphates/FFA + stored - Inhibition of FFA release into blood Glucagon (post absorptive state + during exercise) - ^ lipolysis in adipose tissue - Mobilisation of triglycerides for ATP production
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Comparative metabolism
Insulin:glucagon determines net effect - Absorptive state - high ratio - Post absorptive state - low ratio Ruminants require gluconeogenesis to occur in both absorptive + post-absorptive state as primary source of energy is VFAs not glucose - Propionic acid/amino acids serve as pre-cursor for glucose in absorptive state - Amino acids/glycerol serve as pre-cursors for glucose in post-absorptive state - Utilisation/production of glucose reduced - Proteins/lipids mobilised - Insulin:glucagon remains relatively low + constant
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Carnivores adaption to diet
Dog/cat - Predators/scavengers - High energy content - Easily digestible - Simple digestive tract - Long interval between short meals - Spacious stomach for storage
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Ominvore adaptation to diet
Pigs/bears Best of both worlds Diet consist of plant/animal origin Large species variation in digestive tract - Bears range from herbivore to carnivores - Degree of fermentation occurs in LI
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Herbivore adaptation to diet
Ruminants/horses - Browsers or grazers - Low energy content - Microbial digestion - Digestive tract adapted for fermentation - Continuous eating - 2 digestive strategies - Foregut fermenters - Hindgut fermenters
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Fermentation
Non-hydrolysable carbohydrate requires anaerobic, microbial degradation Long, slow process Digestive tract adapted: - To allow microbial population to thrive - To ensure slow transit of food to allow fermentation
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Foregut fermenters
Ruminants Stomach modified into fermentation chamber Very efficient fermentation Fermentation products absorbed in stomach Microbial protein can pass into abomasum + SI for digestion/absorption
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Hindgut fermenters
Horses/rabbits LI modified into fermentation chamber Moderately efficient fermentation Fermentation products absorbed in colon Microbial protein lost in faeces - Rabbits practice coprophagy
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Comparative fermentation
Hindgut fermentation 70% as efficient as foregut fermentation - Microbes less efficient - Less amylolytic fermentation - Hindgut fermenters lose microbial protein in faeces BUT Gut transit time in foregut fermenters dependent on rate of fermentation and can't be reduced according to nutrient quality of the fibre Horses on abundant poor quality forage can decrease gut transit time and consume more - Ruminants more efficient on good quality forage - Horses ore efficient on abundant poor quality forage - If forage is in short supply, ruminants predominate
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Ruminant nutritional strategies
Fruit, seeds, buds, young + leaves high in hydrolysable carbohydrate (simple sugars) Stems, blades, older leaves high in fibre (complex carbohydrates) Ruminants have 3 nutritional strategies: - Browsers (concentrate selectors) - e.g smallest ruminants, giraffes, most deer - Grazers (grass/roughage eaters) - e.g cattle, sheep, hippos - Intermediates (adaptable feeders) - e.g goats, elk, moose, reindeer, camels
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Browsers ruminant adaptation
Narrow muzzles More mobile lips/tongue Smaller forestomach Ruminant browsers retain functional oesophageal/ventricular groove SI glucose absorption remains high
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Grazers ruminant adaptation
Wide muzzles Less mobile lips/tongue Larger forestomach Ruminant grazers lose functional oesophageal/ventricular groove SI glucose absorption declines
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Oesophageal/ventricular groove
Present in all young ruminants Enables milk to bypass fermentation chamber Grazer ruminants lose groove function by weaning Browser ruminants retain groove function to allow diet high in hydrolysable carbohydrate to escape fermentation - Normal digestion/absorption of hCHO yields more energy than fermentation
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Herbivore glucose absorption
SI is site of glucose absorption via SGLT1 SGLT1 is regulated by diet - High in young, declines in grazers at weaning - Remains high in browsers
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Comparative digestion
Carnivores - No salivary amylase - High levels of enzymes from stomach/pancreas for proteins + fat Omnivores - High levels of salivary amylase - High levels of enzymes from stomach/pancreas for proteins, fat + carbohydrate Simple stomached herbivores - Moderate levels of enzymes for carbohydrate prior to fermentation in LI - Exploited in feeding concentrate diets high in hCHO Ruminant herbivores - Low levels of enzymes for carbohydrate after fermentation in forestomach - Moderate levels of enzymes for protein digestion of microbial protein in abomasum/SI
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Comparative absorption
Carnivores/omnivores - Monosaccharides/peptides/monoglycerides + fatty acids absorbed in SI Simple stomached herbivores - Monosaccharides/peptides absorbed in SI - VFA absorbed in LI Ruminant herbivores - VFA absorbed in forestomach - Peptides absorbed in SI
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Deglutition
Swallowing
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Regurgitation
Passive transfer of stomach contents to oral cavity for re-mastication
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Re-mastication
Additional chewing of fibrous material that has been regurgitated
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Rumination
The entire process of regurgitation, re-mastication and re-deglutition
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Ruminant adaptation to diet
Ruminant stomach adapted for fermentation of roughage/fibre Enlargement of the oesophageal area = forestomach (3 compartments) - Reticulum - Rumen - Omasum Fourth compartment equivalent to simple stomach - Abomasum
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Reticulum/rumen
Reticulum - Inner surface raised to ridges - Strong wall (smooth muscle) - Capacity = 10-20 litres Rumen - Longitudinal groove/pillar divides it into dorsal + ventral sac - Walls contain smooth muscle for contraction - Papillae - Absorption of H2O, VFAs, ion - Papillae increase SA:V - No smooth muscle immobile - Neural plexuses - Regulate contraction via short reflexes (within stomach wall) - Modified by long reflexes (via vagus)
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Histology of forestomach wall
Stratifiet squamous epithelium - Stratum corner (keratinised layer) - Stratum granulosum (tight junctions to limit diffusion) - Stratum basale (cell division occurs, cells migrate towards lumen) - Capillaries (absorption of diffused substances, blood flow increases 3-4x after feeding)
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Omasum
Located on right side Reticulo-omasal orifice regulates passage of fermented material from rumen Multiple leaves with papillae - Increase surface area - More leaves/papillae in grazers cf browsers
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Abomasum
Functions like true stomach Columnar epithelium with glands - HCl - Pepsinogen - Rennin (young ruminants) - Ppts/coagulates casein - Retains milk in abomasum longer for action of pepsin Receives fairly constant flow of fermented material from omasum - Distension inhibits rumino-reticular contractions - Regulation of emptying as in simple stomach pH slightly higher than simple stomach due to alkalinity of fermentation fluid - Still low enough to kill ruminal microbes for digestion
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Distribution of digestive components
Forage must be reduced in size to allow microbial fermentation Distribution of forage in rumino-reticulum of grazers depends on density - Very dense particles (stones/wire) fall straight into reticulum where they usually remain - Density of other particles depends on associated gas from their fermentation - Large particles float in bottom of dorsal sac at level of oesophagus - More dense particles sink into reticulum/cranio-dorsal blind sac/ventral sac - Gas from fermentation collects at top of dorsal sac Distribution in browsers less defined as more homogenous + rapid fermentation occurs throughout rumino-reticulum
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Rumino-reticulum contraction
3 types Primary (mixing of contents) - 5-8 strong contractions/5 mins during eating - 4-5 contractions/5 mins during rumination - 0-1 weak contractions/5 mins during fasting Secondary (eructation) - Occur after every 2-3 primary contractions Rumination - Extra reticular contraction precedes primary contraction
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Primary contractions
1) First reticular contraction - Coarse material towards central/dorsal rumen 2) Second reticular contraction - Fermented material into cranial blind sac - Small volumes fermented material through reticule omasal orifice into omasum 3) Cranial blind sac contraction - Moderately fermented material passes into dorsal sac - Well fermented material passes into reticulum Dorsal sac contraction - Backward contraction - Overall circular movement of contents in dorsal sac - Some exchange with ventral sac 4) Ventral sac contraction - Backward contraction - Overall circular movement of contents in ventral sac - Some exchange with dorsal sac - Well fermented material spills over into cranial blind sac
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Summary of primary contractions
1) First reticular contraction - Coarse material to dorsal sac 2) Second reticular contraction - Fine material to cranial blind sac - FIne materiał to omasum 3) Dorsal rumen contraction - Fine material from cranial blind sac to reticulum - Coarse material circled - Some exchange with ventral sac 4) Ventral rumen contraction - Fine material circled - Some fine material into cranial blind sac - Some exchange with dorsal sac
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Rumination contractions
Rumination occurs when coarse material stimulates oesophageal opening An extra reticular contraction precedes the normal biphasic reticular contractions Normal primary contractions then follow Rumination occurs 6-10 times a day requiring ~60 mins/kg roughage eaten Rumination generally occurs at night and during afternoon rest period Ruminants need to ruminate
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Rumination
Newly swallowed material forced into dorsal sac and replaced by partial fermented material Thorax expands generating -ve pressure in oesophagus Lower oesophageal sphincter opens Diaphragmatic muscle contractions force material into oesophagus - cf abdominal contractions in vomiting Reverse peristaltic oesophageal contractions convey material to oral cavity Liquid immediately re-swallowed Rest of material re-chewed with addition salivary secretion and re-swallowed
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Contractions with eructation (secondary contractions)
2000-4000 litres gas from fermentation per day Occurs after 2-3 primary contractions Oesophageal opening usually below level of gas; gas can't escape during rumination Eructation can't occur with animal lying on side - Makes general anaesthesia/surgery complicated
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Eructation
Primary contractions occur as normal Caudo-dorsal blind sac contracts forward displacing contents into relaxed cranial blind sac and ventral sac Dorsal sac continues contraction and moves gas at top of dorsal sac to oesophageal opening - Increased -ve pressure in thorax causes oesophagus to expand - Cardiac sphincter opens and gas escapes into oesophagus, reverse peristalsis carrying gas to oral cavity - Some escapes via mouth but most inhaled Ventral sac contraction allows gas collecting in caudal-ventral blind sac to escape to the top of the dorsal sac of the rumen
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Bloat
Failure to eructate results in bloat - Complete oesophageal obstruction - Partial oesophageal obstruction - Fresh clover results in small bubbles that fail to coalesce, form a foam that doesn't collect in the dorsal sac so can't be eructated Increased ruminal pressure causes respiratory/caardiac distress Stretching of rumen reduces/stops ruminal contractions
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Regulation of forestomach mobility
Occurs mainly by autonomic long reflexes Both afferent + efferent fibres travel in vagus - Vago-vasal reflex 2 types of sensory cell containing: - Tension receptors - Mechano + chemo-receptors
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Regulation of forestomach motility 2
Stimulation - tension receptor containing cells - In series with smooth muscle cells + sensitive to moderate stretch of rumen walls - Concentrated around oesophageal opening, oesophageal groove, reticulum wall, rumen pillars + cranio-dorsal blind sac wall - Increase motility Inhibition - Mechano/chemorecptor containing cells - Sensity to severe stretch, pH, osmolarity + VFA concentration - Located in basal layer of rumen epithelium - Decrease motility
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Normal increased motility of forestomach
Moderate distension of forestomach Sensed by tension receptor containing cells Motility + rumination increased Food particles broken down more quickly Sub-group of sensors around reticule-omasal orifice - Release vasoactive intestinal peptide - Relaxation of reticulo-omasal sphincter during 2nd reticular contraction Increases rate of passage of food
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Normal decreased motility of forestomach
Increased [VFA]/increased osmolarity/consequent decreased pH Sensed by chemoreceptor containing cells Motility + rumination decreased Food particles broken down more slowly Decreases passage rate of food
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Abnormal motility of forestomach
Severe distension - e.g during bloat Very low pH <5 - e.g during grain engorgement Motility decreased Decreased passage rate of food
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Central control of forestomach motility
Dorsal vagal nuclei in medulla 2 sets of nerve clusters that regulate: - Frequency of ruminal contractions/rumination - Force of ruminal contractions Also recieves input from olfactory organ, tastebuds + oral cavity stretch recptors Stress causes severe reduction in motility via central control Strength of ruminal contraction s+ frequency of rumination/ruminal contractions good indicator of general wellbeing
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Development of forestomach
At birth, abomasum developed but not forestomach Forestomach develops when lamb starts to eat more roughage at ~2-3 wks Microbes for fermentation develop too but lamb still dependent on milk for nutrition - Recieved mainly from mother by licking - why bonding so important Milk bypasses fermentation chamber via oesophageal groove
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Oesophageal groove
Referred to as reticular/ventricular groove Groove with lops that runs from oesophagus to reticulo-omasal orifice When animal sucks warm milk, reflex causes lips to curl over forming a tube - Cold milk prevents complete curling over and can then spill into reticulo-rumen Milk passes from oesophagus dirct to omasum then abomasum for digestion; avoiding fermentation by developing rumen - If milk intake>capacity of tube, it spills over into the rumino-reticulum and is fermented - Lactose rermented to lactate etc - Adverse effect on developing microbes Sucking and chemorecptors in pharynx sensitive to milk compounds cause reflex closure of groove - Can also be stimulated by certain salt solutions used to prepare oral medication that bypasses fermentation chamber Reflex lost when animal weaned - Retained if milk is still fed - Retained in browsers
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Ruminant fermentation
Most plant material can't b e digested by mammalian enzymes Requires microbial fermentation - Ferment food components for their own growth, division + motility - End products of fermentation used by host Rumino-reticulum - Physiologically function together - Provide environment for microbial population - Delay gut transit time to allow sufficient time for fermentation
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Provision of anaerobic environment (for fermentation
Oxygen can gain entry to ruminoreticulum from: - Blood supply - Swallowed air Under aerobic conditions, food sustances would be completely broken down to CO2 + H2O which don't provide energy to the host Anaerobic contitions prevent total degradation resulting in metabolites that host can use for energy Certain anaerobic bacteria can use O2 (facultative anaerobes) - Adhere to luminal surface - Remove all O2; rendering environment anaerobic
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Microbes for fermentation
Most are bacteria Protozoa much larger so contribute almost equally to microbial mass Environment physically/chemically regulated - Density + competitive balance between microbes remains stable provided feeding pattern is stable - Too rapid change in ingested food will upset balance In order to establish microbes must be retained in rumen for sufficient time to allow proliferation - Ruminal contents are ejected from rumen after fermentation - Amyolytic bacteria have short lifespan, exist in fluid phase and not retained for long - Cellulolytic bacteria/protozoa/fungi have longer lifespan so must be retained longer to establish - Achieve this by adhering to luminal wall/fibre
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Establishment of ecosystem
When newly born gut is sterile Microbes must be ingested All environmental microbes are ingested but ruminal ones establish - Due to rumination mother's oral cavity contains representative populations of ruminal microbes - Transferred to young by licking/grooming - If neotate isolated, will gradually establish bacterial but not protozoal populations Ruminal microbes adapted to rumen environment so have competitive advantage over other microbes
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Rumen bacteria
Classified on basis of nutrients metabolised Amylolytic - Starch/hHCO -> monosaccharides - High tolerance of low pH - Can proliferate very quickly at expense of other microbes Cellulolytic - Cellulose, hemi-cellulose, fructosans, pectin -> monosaccharides - Low tolerance of low pH Proteolytic - Protein -> Peptides -> amino acids, used for microbial protein synthesis for fermented -> VFAs + NH4+ Methanogenic - CO2 -> CH4 Lactate-utilisers - Lactate -> propionate
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Protozoa/fungi
Protozoa - Mostly ciliates, much larger than bacteria (can engulf bacteria) - Retained longer in rumen by adhering to large feed particles - Produce VFAs, lactate, CO2 + H2 - Proliferate with high starch diets, reduced with high fibre diets - Store glucose as glycogen - This glucose can be recovered when protozoa pass into SI and are digested - Ruminants can survive without protozoa but fermentation much more efficient in their presence Fungi - Represent small proportion of microbial population - Reproduce by free-swimming flagellated spores - Can only break down lignin aerobically - Rumen under anaerobic conditions - Lignin indigestible but presumed that spores attach to lignin and split it apart by hyphae, rendering it susceptible to cellulytic digestion - Proliferate with diets high in lignin
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Homeostasis of rumen environment
Food fermented into metabolites (mainly VFAs + NH4+) Osmolarity ^/pH decrease Water enters rumen by osmosis NH4+ taken up by microbes VFAs absorbed by host Increased rumination/HCO3- Osmolarity lower/pH ^ Water reabsorbed
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Rumen acidosis
Consumption of increased levels of hCHO VFAs ^^/pH lowered If pH decreases too much, acid-resistant lactate producers proliferate at expense of lactate utilisers Lactate poorly absorbed cf VFAs Too low pH injuries rumen epithelium Water enters rumen osmosis Dehydration/hypovolaemic shock ensues Treated by iv alkaline fluids Can be prevented by introducing levels hCHO gradually (3-4 wks) to enable lactate utilisers to increase in level with lactate producers
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Ruminant metabolism
Ruminant fermentation very efficient - Only 10% feed energy lost Rate of fermentation dependant on - Type of feedstuff - Starch fermented more rapidly than fibre - Volume of feedstuff - Microbial balance - Amylolytic bacteria ferment faster than cellulolytic Homeostatic environment must be maintained by equivalent metabolism of different food components/products of fermentation Rumen microbes can degrade many toxins before their absorption cf simple stomached animals - Foxglove leaves (digitalis) - Ragwort
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Carbohydrate metabolism (ruminants)
Plants contain many different CHO that can be broken down by microbes Bacterial surface enzymes break down cellulose + starch > monosaccharides/short chained polysaccharides Dissolved in rumen fluid but not available to host as immediately taken up by microbes and metabolised via glycolysis - In mammalian cells under aerobic conditions, glycolysis proceeds to CO2 + H20 - As rumen is anaerobic glycolysis can only proceed as far as VFAs VFAs end products/waste products for microbes but main source of energy for ruminants Propionate can be formed via 2 metabolic pathways - Via anaerobic glycolysis of pyruvate - From lactate Increased levels of starch enable proliferation of lactate utilisers so high starch diets - Increase overall VFA production - Increase relative propionate production Important as CHO represents 85% total energy from typical diets but only propionic acid (20% total VFA) can be converted to glucose in host cells
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Methane production (ruminants)
CH4 rich in energy Represents ~10% energy loss from total food energy BUT - Glycolysis requires reduction of NAD+ - NAD+ must be regenerated - Under aerobic conditions in animal cells this ice achieved via respiratory chain - But rumen environment is anaerobic - Methane producers reduce CO2 -> CH4 via oxidation of NADH -> NAD+ - Reduce H+ ions; increase pH - Replenish NAD+ suplies for glycolysis - NAD+ can also be regenerated by reduction of sulphate/nitrates by other ruminal bacteria
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Fat metabolism (ruminants)
Long chain fatty acids - Free form - Triglycerides - Galacto-lipids Rapidly hydrolysed galactose/glycerol parts fermented to VFAs (mainly propionic acid) Most poly-unsaturated fatty acids hydrogenated to mono-unsaturated or saturated fatty acids - Most common are oleic acid and linoleic acid -> stearic acid Unsaturated fatty acids synthesised as stereoisomeric cis form in animal tissue Rumen bacterial hydrogenation also generates some trans unsaturated fatty acids - why ruminant body fat differs to other species
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Protein metabolism (ruminants)
Protein degraded by ruminal bacteria into: - Peptides - Amino acids - NH3 + organic acids - Branched fatty acids - Stimulate growth of cellulolytic bacteria Microbial proliferation requires high rate of protein synthesis - Mostly derived from inorganic nitrogen - Also from non-protein nitrogen in food + additives - Cellulolytic bacteria require NH4+ - Amylolytic use both NH4+ + amino acids
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Metabolism of non protein nitrogen
NPN consists of amides, amines, peptides, amino acids, nucleic acids, urea, nitrates + ammonium ions Ruminants can utilise NPN for protein synthesis via microbes - NPN -> NH3 -> amino acids -> protein - Microbial protein digested in stomach/SI as in simple-stomached animals NPN essential for healthy microbial population - Grass/grain contains 5-15% NPN - Silage contains 70% NPN (due to microbial fermentation)
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Lactation requirements (ruminants)
Ruminants can function normally if nitrogen only supplied as NPN High producing dairy cows require more than microbial protein - Urea often added to diets to increase NPN - Increases microbial population so protein available for digestion - Microbes must be supplied with extra energy in order to proliferate - Extra protein added to diets - Escape fermentation as poorly soluble - Passes into abomasum/SI for digestion XS protein recycled into urea and secreted in saliva XS urea excreted by kidneys - Energy costly so feed should only contain slightly more NPN than microbes require
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Absorption (ruminants)
Selective transfer of useful nutrients into host's bloodstream Reticula-rumen enhances this by papillae, increasing SA - Papillae most dense in parts of rumen responsible for absorption (ventral sac + cranial/caudal-dorsal blind sacs) Requires specific transport proteins and energy source Feed material must be digested to sufficient size to enable absorption - Mainly VFAs Monosaccharides/di/tri-peptides/amino acids unavailable to host as immediately taken up by microbes
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Rumen absorption
VFAs - ~80% total VFAs absorbed - Stratum corneum permeable to anion/un-dissociated acid - Stratum glanulosum only permeable to un-dissociated acid - Rumen pH decreases as fermentation proceeds, un0dissociated form conc increases - BUT at normal rumen pH anion form predominates - Postulated that some H+ producing mechanism in epithelium causes local increase in un-dissociated form , enabling absorption - Acetic acid absorbed unchanged - Some propionic acid metabolised to lactic acid as absorbed - All butyric acid metabolised to β-hydroxybutyric acid as absorbed Water - Moves between rumen content/ECF depending on osmotic gradient Lactic acid - Stronger acid so more poorly absorbed than VFAs - Tends to remain in rumen, lowering pH - When absorbed, converted to glucose by liver Ammonia - NH4+ prodominates but NH3 rapidly absorbed so equilibrium continually shifting to NH3 form - When absorbed converted to urea by liver Inorganic ions - Rumen -ve reliable to blood - hinders absorption of +ve ions - Na+/Mg2+ actively transported to blood - Cl- absorbed in exchanged for bicarbonate - Ca2+/PO42- mainly absorbed in SI
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Omasal absorption
SA increased by leaves/papillae Fermentation continues in omasum Absorption of ~10% total VFA leaving 10% passing into omasum Water/Na+ also absorbed - Ingesta so more solid than in rumen - Contains less HCO3- so abomasum needs to secrete less H+ Some rumen material passes straight into absorption via omasal canal
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Functional anatomy of the hors
Ascending colon castle modified into fermentation chamber - 3 compartments separated by physiological valves - Caecum separated from ventral colon by caeca-colic valve - also separated from ileum by ileo-caecal valve - Ventral colon separated from dorsal colon by narrow pelvic flexure - Dorsal colon separated from small colon by narrowing transverse colon Transverse colon relatively short and narrows down to meet descending colon Longitudinal muscle not continuous strand but arranged into taenial bands - Different number of taenia in different parts - Shorter than large intestine itself resulting in sacculations - Enable mixing and delays transit time to allow fermentation
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Fermentation (equine LI)
Similar process to that occurring in ruminant forestomach Degree of fermentation depends on material reaching LI - In carnivores most digestion/absorption has already occurred prior to LI so fermentation minimal - In ruminants/omnivores, fermentation moderate - In horses vast majority of non hydrolysable CHO reaches LI so fermentation extensive Microbial products of fermentation are VFAs/CH4/CO2 - LI mucosa can absorb these VFAs - Gasses passed to rectum by peristalsis and expelled Microbial balance can be easily upset, just as in ruminants As LI is terminal part of GI tract some VFAs and all microbial protein egested/wasted - Rabbits/rats practice coprophagy to avoid this waste
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Metabolism of VFAs (Equine LI)
Energy sources - Especially in horse 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 lipid synthesis Propionate - Substrate for gluconeogenesis Butyrate - Energy production - Cellular homeostasis
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Absorption (equine LI)
VFAs (accettate, propionate, butyrate) - Absorbed by SCFA/HCO3- exchanger Na+ - Absorbed by Na channels + Na+/H+ exchanger - Sodium absoption enhanced by aldosterone Cl- - Absorbed by bicarbonate/hydroxyl exchange Water - Most of water passing from SI absorbed in LI - Osmotic pressure - Hydrostatic pressure - Solvent drag - Extensive reabsorption in horses
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Comparative physiology (equine)
LI physiology similar in most domestic species except horse In feral horse on grass diet, 75% energy derived from VFAs produced by microbial fermentation in hindgut Fermentation similar process to in ruminant forestomach - BUT SI occurs before fermentation vessel - In ruminants, any hCHO immediately fermented so none passes into SI - However in horse potentially lots of hCHO can pass into LI if overload of SI capacity to digest/absorb it
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Carbohydrate fermentation (equine)
Fibre requires microbial fermentation Products of fermentation are mainly VFAs VFAs cause a decline in pH of luminal contents - Neutralised by copious pancreatic secretion containing HCO3- - Goblet cells in LI secrete mucus + HCO3- - Ileum also secretes HCO3- If production of VFAs excessive H= ions too numerous to be neutralised by HCO3- secretions - pH of luminal contents declines - Favours multiplication of acid resistant microbes - Lactic acid poorly absorbed cf CFAs causing further pH decline
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Protein fermentation (equine)
Probably similar to ruminants BUT Equine hindgut more capable of absorbing amino acids/peptides Less amino acids/peptides taken up by microbes, more being absorbed by the host Good thing as microbial protein is lost in faeces in hindgut fermenters Microbial nitrogen requirements satisfied by urea secreted by ileum/LI - Broken down by microbial urease into NH3 to be used as NPN source for microbial protein synthesis
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Water absorption (equine)
Compared to other species more water reabsorption occurs in large intestine At luminal pH (6.5) most VFAs in ionic form which are poorly absorbed Local mechanism of secretion of H+ in exchange for Na+ converts ions to their respective acids, enhancing their absorption HCO3- secreted in exchange for Cl- maintain pH at level suitable for fermentation Consequently when VFAs absorbed there is also a net absorption of NaCl which enhance water reabsorption via osmotic pressure + solvent drag
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VFA absorption
Compared to ruminants VFAs are absorbed intact rather than metabolised as they're absorbed As in ruminants, proportion of propionic acid increases with more hCHO passing into LI - Substrate for amylolytic bacteria causing their proliferation - But hCHO mustn't be fed excessively otherwise it will disturb the microbial balance - With dietary adaptation SI digestion/absorption of hCHO can increase to prevent overload - Much more energy efficient to digest hCHO and absorb as glucose rather than ferment it to propionic acid for gluconeogenesis
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Microbiology (equine)
Bacteria - Food material passing into fermentation chamber generally contains lower levels of hCHO - Amylolytic population lower so fermentation slower Protozoa - Ciliates as in ruminant but different species - Smaller number than bacteria but larger - contribute similar total mass - Contribution to fermentation unknown - If removed, very little difference to fermentation efficiency - Protozoa lost in faeces so can't be digested as in ruminant Fungi - Probably similar to ruminants - Split apart lignin, rendering it susceptible to digestion by celluloyti bacteria
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Foregut vs hindgut fermentation
Hindgut fermentation 70% as efficient as foregut fermentation - Microbes less efficient - Lower degree of amylolytic fermentation - Hindgut fermenters lose microbial protein in faeces - coprophagy - rabbits BUT Gut transit time in foregut fermenters dependent on rate of fermentation and can't be reduced whatever the nutrient quality of the fibre Horses on poor quality forage can decrease gut transit time and consume more - Ruminants more efficient on good quality forage - Horses more efficient on poor quality forage as long as its in abundance
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Motility (equine LI)
Large intestinal transit time must be slow enough to allow fermentation to occur - Hindgut fermenters - several days - Foregut fermenters - 24 hours In most species, caecum + colon form continuous compartment - In horses, caecum separated from colon by caeco-colic valve - Separate fermentation compartment with no retrograde flow of material from colon to caecum
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Caecal contractions (equine)
Segmental contractions main type - Maintains high microbial activity for fermentation + absorption Mass contractions occur every 3-5 mins - Coordinated contraction of entire caecum - Mass evacuation of caecal contents into colon - Similar to peristaltic contractions but smooth muscle contracts for longer
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Colonic contractions
Most species - Main contractions are segmental, peristaltic + anti-peristaltic - Anti-peristaltic contractions more prominent in proximal colon - Retrograde movement of chyme from colon into caecum EXCEPT in horse - No retrograde movement from colon into caecum - Anti-peristaltic contractions occur principally in distal part of ventral colon - Slow movement of passage of chyme from ventral to dorsal colon via pelvic flexure - Only small particle/well fermented material can pass via pelvic flexure into dorsal colon - Ensures slow enough transit time to allow efficient fermentation Omnivores/carnivores also have mass movement contractions in colon for evacuation
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Equine colic
Not a disease but a clinical sign of abdominal pain - True colic - GI pain - False colic - other abdominal organ pain Colic results in the highest levels of equine mortality + morbidity so an accurate diagnosis is essential to treat successfully The most useful procedure in diagnosis is rectal examination
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Normal sounds in equine abdominal auscultation
Left dorsal - SI/small colon - Fluidy in nature, higher pitch Left ventral - pelvic flexure Right dorsal/ventral - caecum - Loud, toilet flushing sound
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Abnormal sounds in equine abdominal auscultation
Increased frequency - Enteritis - Spasmodic colic Tympanitic - Gut distension with gas - Obstruction Decreased frequency - Ileus - Obstruction
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Normal equine rectal examination
Spleen lying against left abdominal wall Caudal pole of left kidney dorsal and left of midline - Nephro-splenic ligament/nephro-splenic space palpable between the above Caecum to right of midline - Ventral taenia extending from upper right to ventral midline Aorta in dorsal midline Root of the mesentary in dorsal midline running ventrally Pelvic flexure lying left ventral Small colon containing faecal pellets lying left dorsally - SI not usually directly palpable unless it contracts during palpation
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Equine rectal exam - SI obstruction
Normally can't feel SI as it is empty If distended by gas, inicator of obstruction SI obstruction causes dehydration of large colon contents - Feels hard + vacuum wrapped - Distinguish from primary large colon impaction
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Equine rectal exam - Ileal impaction
Firm tubular structure in centre of abdomen coursing towards caecum If detected early, SI distension minimal If detected late, SI will be distended
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Equine rectal exam - Caecal impaction
Primary - impaction with ingesta Secondary - to obstruction of large colon Taenia become more taut Caecum displace more to midline
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Equine rectal exam - Colonic impaction
Most commonly occurs at pelvic flexure Obvious palpable mass in left ventral quadrant - Large colon feels enlarged Usually can be treaded medically - cf secondary impactions
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Equine rectal exam - Left dorsal displacement
Also called nephro/reno-splenic entrapment Left colon passes to left of spleen and becomes trapped over nephro-splenic ligament Left colon palpable on left and dorsally If long-standing left colon becomes too distended to palpate nephro-splenic ligament
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Equine rectal exam - right dorsal displacement
Left colon displaced lateral to caecum Pelvic flexure usually ends up in left cranial abdomen beyond reach Caecum displaced cranio-medially and becomes more difficult to palpate
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Equine rectal exam - large colon volvulus/torsion
Abdomen visibly distended Large colon fills entire abdomen - Often can't advance arm into abdomen beyond pelvic rim Colon markedly distended Volvulus occurs first but often associated with torsion + consequent vascular compromise
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