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ACVIM SAIM (2023) > GI | Liver | Pancreas > Flashcards

GI | Liver | Pancreas Flashcards

1
Q

What are the layers of the GI wall?

A
  1. Serosa
  2. Longitudinal smooth muscle layer
  3. Circular smooth muscle layer
  4. Submucosa
  5. Mucosa (bundles of smooth muscle fibers)
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2
Q

What are slow waves in the GIT?

A

Rhythmic contractions - determine by frequency of slow waves (NOT AP but slow undulating changes in resting membrane potential)
Varies along GIT

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3
Q

What cells are consider the electrical pacemakers for smooth muscle cells?

A

Interstitial cells of Cajal - Undergo cyclic change in membrane potential
Unique ion channels that periodically open = inward pacemarkers currents

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4
Q

Do the slow waves in the GIT cause muscle contraction?

A

NO! Except in stomach. Provide electrical background to allow AP when excited by intermittent spike potentials (which excites muscle contractions)

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5
Q

What are spike potentials in GIT?

A

True AP - Each time peaks of slow waves temporarily more + spike potentials = Peaks

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6
Q

In the nerve fibers how are AP generated?

A

By rapid entry of Na into nerve through Na channels

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7
Q

How are the action potentials different in the GIT?

A

Calcium-sodium channels = Much slower to open/close = Longer duration of AP

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8
Q

What are the 3 main actions that can result in depolarization of smooth muscle cells in GIT?

A
  1. Stretching of muscle
  2. Stimulation by acetylcholine release from parasympathetic nn
  3. Stimulation by several specific GI hormones
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9
Q

What are the effects of norepinephrine and epinephrine on GIT nerves (stimulation of smpathetic nn)?

A

More negative = Hyperpolarized (less excitable)

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10
Q

What causes Ca to enter the muscle fiber to result in a contraction?

A

Slow waves do NOT cause Ca to enter (ONLY Na), thus no muscle contraction alone
During a spike potential (generated by slow waves) = Large amount of Ca enters = muscle contraction

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11
Q

What are tonic contractions in the GIT?

A

Continuous (not associated with slow waves) - can last mins to hours
These are in addition or instead of rhythmical contractions

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12
Q

What is the nervous system that is within the wall of the gut?

A

Enteric Nervous System

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13
Q

What are the two major plexus and what do they control?

A
  1. Myenteric Plexus (Auerbach’s): Outer plexus twn longitudinal and circular muscle layers - mainly control GI movements
  2. Submucosal Plexus (Meissner’s): Inner plexus - controls mainly GI secretions and local blood flow
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14
Q

Which plexus in GIT controls GI movements?

A

Myenteric Plexus (Auerbach’s)

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15
Q

Which plexus in GIT controls GI secretions and local blood flow?

A

Submucosal Plexus (Meissner’s)

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16
Q

What is the main difference btwn the myenteric and submucosal plexuese?

A

Myenteric Plexus = Linear chain of interconnected neurons that run the length of GIT - Control muscle activity along length of gut
Submucosal Plexus = Functions within the inner wall of each segment of intestine, sensory signal from epithelium integrate at submucosal plexus to help control intestinal secretions, local absorption, location contraction of submucosal muscle

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17
Q

What is the neurotransmitters that results in excitation in GIT?

A

Acetylcholine

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18
Q

What is the neurotransmitters that results in inhibition in GIT?

A

Norepinephrine

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19
Q

How does parasympathetic stimulation affect the ENS?

A

Increases activity of ENS

Mainly vagus nn (some through pelvic nn)

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20
Q

How does sympathetic stimulation affect the ENS?

A

Inhibits GIT activity = From T5-L2 → sympathetic chains → celiac ganglion → mesenteric ganglia (postganglion neuron bodies) → Postganglic fibers to ENTIRE GIT → Secrete norepinephrine (small amounts of epinephrine)
Inhibits intestinal smooth muscle, blocks/inhibits neurons in ENS

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21
Q

What is the gastrocolic reflex?

A

Signals from stomach to cause evacuation of colon (reflex from gut to prevertebral sympathetic ganglia back to GIT)

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22
Q

What is the enterogastric reflex?

A

Signals from colon/small intestines to inhibit stomach motility and secretions (reflex from gut to prevertebral sympathetic ganglia back to GIT)

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23
Q

What is the colonoileal reflex?

A

Reflexes from colon to inhibit emptying of ileal contents into colon (reflex from gut to prevertebral sympathetic ganglia back to GIT)

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24
Q

What is a reflex that comes from the GIT to spinal cord/brain and then back to GIT?

A

Defecation reflexes = from colon/rectum to spinal cords and back to produce powerful colon, rectal, and abdominal contractions = Defecation

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25
Q

Where is gastrin produced?

A

G cells from antrum, duodenum, jejunum

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26
Q

What are the 2 actions of gastrin?

A

Stimulates:

  1. Gastric acid secretion
  2. Growth of gastric mucosa
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27
Q

Name 3 stimuli that result in secretion of gastrin?

A
  1. Protein
  2. Distension
  3. Nerve (gastrin releasing peptide from vagal stimulation)
    Acid = Inhibits release
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28
Q

Where is cholecystokinin secreted?

A

I cells of duodenum, jejunum, and ileum

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29
Q

Name 3 stimuli that result in secretion of cholecystokinin?

A
  1. Protein
  2. Fat
  3. Acid
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30
Q

Name 6 roles of cholecytsokinin.

A 
Stimulates:
1.  Pancreatic enzyme secretion
2.  Pancreatic bicarbonate secretion
3.  BG contraction
4.  Growth of exocrine pancreas
Inhibits:
5.  Gastric emptying (moderate - time for digestion)
6.  Appetite (sensory afferent in duodenum via vagus to appetite centers)
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31
Q

Where is secretin secreted from?

A

S cells from duodenum, jejunum, ileum

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32
Q

What are 2 stimuli for secretion of secretin?

A
  1. Acid

2. Fat

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33
Q

Name 4 things that are stimulated and 1 thing that is inhibited by secretin.

A 
Stimulates:
1.  Pepsin secretion
2.  Pancreatic bicarbonate secretion!!! (neutralizes acidic contents)
3.  Biliary bicarbonate secretion
4.  Growth of exocrine pancrease
Inhibits:
1.  Gastric Acid secretion
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34
Q

What cells secrete gastric inhibitory peptide (GIP)?

A

K cells of duodenum and jejunum

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35
Q

What are 3 stimuli for gastric inhibitory peptide (GIP) secretion?

A
  1. Protein
  2. Fat
  3. Carbohydrates (less)
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36
Q

Name 1 thing that is stimulated and 2 things that are inhibited by gastric inhibitory peptide (GIP)?

A 
Stimulates:
1.  Insulin release
Inhibits:
1.  Gastric motility (mild)
2.  Gastric Acid Secretion
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37
Q

What is another name for gastric inhibitory peptide (GIP)?

A

Glucose-dependent insulinotrophic peptide

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38
Q

Which cells secrete motilin?

A

M cells of stomach, duodenum, jejunum

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39
Q

Name 3 things that stimulate the secretion of motilin.

A
  1. Fat
  2. Acid
  3. Nerve
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40
Q

What does motilin do in GIT?

A

Stimulates gastric and intestinal motility (cyclic release = waves → interdigestive myoelectrical complexes

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41
Q

What are the 2 types of movement in the GIT?

A 
Propulsive movements (food to move to accommodate digestion/absorptive)
2.  Mixing movements (of contents)
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42
Q

What are the stimuli for propulsive movements = peristalsis in GIT?

A

Stimulus = Distenstion (stretching) caused by material

Some chemical and physical irritation, strong parasympathetic nervous signals

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43
Q

What is the function of the myenteric plexus in peristalsis?

A

If no myenterix plexus (congenital) peristalsis will NOT occur
Block it with atropine (affecting cholinergic nn in myenteric plexus)

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44
Q

Why are the directional movements of peristalic waves to the anus?

A

Can occur in either direction, but orad dies out = likely related to polarization of myenteric plexus

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45
Q

What is the “law” of the gut?

A

Peristaltic reflex = gut reflexes to result in receptive relaxation (easier propulsion) - Perstaltic waves to the anus

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46
Q

Name 2 mixing movements in the GIT?

A
  1. Peristalsis again sphincter = churning of content

2. Local intermittent constrictive contractions within gut wall (chopping and shearing contents)

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47
Q

What is splanchnic circulation?

A

• Blood flow in gut, spleen, pancreas → liver (via portal vein) → hepatic sinusoids (reticuloendothelial cells to remove bacteria, carbs and proteins absorbed) → hepatic veins → vena cava

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48
Q

Which nutrient is NOT carried in portal blood and why?

A

o Fats absorbed from GIT (not carried in portal blood) into intestinal lymphatics to thoracic duct to systemic circulation

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49
Q

What are the 3 phases of swallowing?

A
  1. Voluntary Stage (bolus into pharynx)
  2. Pharyngeal Stage (involuntary)
  3. Esophageal Stage (involuntary)
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50
Q

What are the 2 types of peristalsis during the esophageal phase?

A
  1. Primary peristalsis - continuous wave from pharynx

2. Secondary Peristalsis = from distension of esophagus (controlled by myenteric NS)

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51
Q

What are the 3 main motor functions of the stomach?

A
  1. Storage of food until into SI
  2. Mixing of food with gastroc secretions into chyme
  3. Slow empyting of chyme from sotmach into SI
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52
Q

What results in relaxation of stomach during the storage function of the stomach?

A

Distension with food → “vasovagal reflex” to brain stem → relaxes stomach wall (to accommodate more food)

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53
Q

Describe the basic electrical rhythm of the stomach.

A

Mixing waves = Slow waves (spontaneous) that result in mixing of the food (chyme), more intense at antrum

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54
Q

What are hunger contractions?

A

When the stomach as been empty for hours - Rhythmic powerful contractions

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55
Q

What controls stomach emptying?

A

“Pyloric pump” - intense peristaltic wave in the antrum, pyloric sphincter also controls this

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56
Q

In general what regulates stomach emptying?

A

Signals from stomach and duodenum (potent)

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57
Q

What are the 2 gastric factors that control stomach emptying?

A

Promote emptying = increased pyloric pump

  1. Gastric food volume (stretch)
  2. Gastrin release
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58
Q

What are the 2 duodenal factor that control stomach emptying?

A

Inhibit Emptying

  1. Enterogastric Relfex (food in duodenum inhibit pyloric pump)
  2. Hormones = CCK (from jejunal cells that sense fat) = Blocks stomach motility (caused by gastrin)
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59
Q

What are the 2 major movements in the SI?

A
  1. Mixing contractions = segmentation contractions (from SI distension with chyme)
  2. Propulsive Movements = Perstaltic waves
    Stretch (chyme in duodenum), gastroenteric reflex, hormones (gastrin, CCK, insulin, motilin, serotonin)
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60
Q

Which hormones increased motility in SI?

A

gastrin, CCK, insulin, motilin, serotonin

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61
Q

Which hormones decreased motility in SI?

A

Secretin and glucagon

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62
Q

What is the gastroielal reflex?

A

After a meal = increased peristalsis in ileum = emptying

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63
Q

What are the 2 major movements of the colon?

A
  1. Mixing movements - large circular contractions

2. Propulsion movements = MASS MOVEMENTS (dt gastrocolic and duodenocolic reflexes = distension)

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64
Q

What are the 2 reflexes that control defecation and which one is “stronger”?

A
  1. Intrinsic Reflex (local ENS - myenteric plexus)

2. Parasympathetic Defecation Relfex (via pelvic nn) = VERY POWERFUL peristalsis and inhibits internal anal sphincter?

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65
Q

Which anal sphincter is under voluntary control?

A

External anal sphincter

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66
Q

Which nerves control the parasympathetic defecation reflex?

A

Pelvic nn

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67
Q

What is the peritoneointstinal reflex?

A

irritation of peritonenum = intestinal paralysis

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68
Q

What is renointestinal reflex and vesicointestinal reflex?

A

Inhibits intestinal activity due to kidney or bladder irritation

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69
Q

What are the two layers of muscles in the GIT?

A
  1. Circular muscles

2. Longitudinal muscles

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70
Q

What is the name of gastrin secreting tumors?

A

Zollinger-Ellison Syndrome within the pancreas

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71
Q

What is a unique feature of the electrical activity of GIT smooth muscle?

A

Slow waves = Not AP but oscillating depolarization and repolarization

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72
Q

What is the action potential in GIT dependent on?

A

Action potentials in GIT cannot occur unless the slow wave brings the membrane potential to threshold

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73
Q

What determines the rate and action potentials and contractions in various segments of GIT?

A

The frequency of slow waves which is controlled by pacemaker = Interstital cells of Cajal

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74
Q

What type of channels control the depolarization and repolarization of the slow waves in GIT?

A

Ca 2+ open resulting in Ca2+ entering cell = Depolarization

K+ open resulting in K+ OUT of cell = Repolarization

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75
Q

What do neural and hormonal input influence in GIT?

A

Neural input and hormonal input DO NOT influence the frequency of slow waves, they do influence the frequency of action potentials

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76
Q

During fasting what type of gastric contraction periodically occurs?

A

Migrating myoelectric complexes = mediated by motiliin

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77
Q

What is another name for pits?

A

Crypts of Lieberkuhn = Secretory cells in GIT

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78
Q

What are the basic steps in secretion from a glandular cell in the GIT?

A
  1. Diffusion of substance from capillaries into glandular cell
  2. Secretory substance made in ER
  3. Formed by ribosomes and Golgi
  4. Stored Glogi vesicles
  5. Increased permeability = Increased intracellular Ca2+ = Vesicles fuse to apical membrane = Exocytosis
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79
Q

What is mucus made of?

A

Water, electrolytes, glycoproteins

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80
Q

What are the 6 magic properties of mucus?

A
  1. Adheres tightly to food and spreads thin
  2. Sufficient body to coat GIT so that food rarely touches mucosa
  3. Causes formation of fecal balls
  4. Resistant to digestion by digestive enzymes
  5. Particles slide along it easily
  6. Amphoteric properties (can buffer acid or alkali)
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81
Q

What are the 2 types of secretions from salivary glands?

A
  1. Serous = Ptyalin (a-amylase) = Digest starch

2. Mucus = Mucin = Lubrication

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82
Q

What is ptyalin?

A

a-Amylase to digest starches, found in salivary secretions are part of serous secretion

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83
Q

What is the primary secretion from salivary glands?

A

Either ptyalin or muscus with same electrolyte composition as ECF

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84
Q

What is the final composition of saliva and where do these changes take place?

A

Within the salivary ducts = HIGH K+ and HCO3- (little Na and Cl)

  1. K+ active secretion
  2. HCO3- secretion
  3. Na active absorption
  4. Cl- passive absorption (follows Na)
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85
Q

What components are in salivary to attack bacteria?

A
  1. Thiocyanate ions
  2. Lysozyme
  3. Ig
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86
Q

What is the primary nerous control of saliva?

A

Parasympathetic = 2 salivary nuclei in brainstem

Stimulated by high centers (appetite) or something on tongue

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87
Q

Discuss the blood flow in the salivary glands.

A

The salivary glands make kalikrein - which when secreted splits a-2 globulin into bradykinin = VASODILATION

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88
Q

What is the primary secretion in the esophagus?

A

MUCUS for Lubrication (simple and compound mucous glands)

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89
Q

What are the two major glands in the stomach and what do each of them secrete?

A
  1. Oxyntic Gland (Gastric Gland) = HCl, Pepsinogen, intrinsic factor, mucus
  2. Pyloric Gland = Mucus, Gastrin
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90
Q

What are the 3 main cell types that make of the gastric/oxyntic gland and what do they secrete?

A
  1. Mucous Neck Cell = Mucus
  2. Oxyntic/Partiel Cells = HCl, intrinsic factor
  3. Peptic/Chief Cells = Pepsinogen
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91
Q

What is the driving force behind secretion of HCl from the oxyntic/parietal cells?

A

H+/K+ ATPase pump on the apical membrane that results in secretion of H+ intot he canaliculus

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92
Q

What are the steps in HCl secretion in a oxyntic/parietal cells?

A
  1. Water dissociates into H+ and OH- in the cytoplasm
  2. H+/K+ ATPase allows H+ to be secreted into the canaliculi
  3. Potassium in brought into the cell on the basolateral membrane by a Na+/K+ ATPase pump, this makes low intracellular Na+, which brings Na+ into the cell from the canaliculus
  4. Pumping out of H+ allows formation of HCO3- since OH- is accumulating in the cell cytoplasm, this is mediated by carbonic anhydrase, this is then secreted in exchange for Cl-, which is sent out into the canaliculus to meet with H+ and make HCl
  5. Water passes into the canaliculus by osmosis
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93
Q

What are the 3 main stimuli for HCl secretion and which cells do these substances stimulate?

A
  1. Acetylcholine = All cells are stimulated
  2. Gastrin = Only parietal cells are stimulated
  3. Histamine = Only parietal cells are stimulated
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94
Q

Which cell type secretes HCl?

A

Oxyntic/parietal cells (part of gastric/oxyntic gland)

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95
Q

Which cell type secretes intrinsic factor (dog)?

A

Oxyntic/parietal cells (part of gastric/oxyntic gland)

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96
Q

Which cell type secretes pepsinogen?

A

Peptic/Chief cells (part of gastric/oxyntic gland)

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97
Q

How is pepsinogen activated?

A

Pepsinogen (inactive) is secreted by the peptic/chief cells in the gastric/oxyntic gland. This is converted to pepsin (ACTIVE = highly proteolytic at low pH) when HCl is present

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98
Q

What stimulates the conversion of pepsinogen into pepsin?

A

HCl

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99
Q

What are the 2 main stimuli for secretion of pepsinogen from peptic/chief cells?

A
  1. Acetylcholine (vagus n. and gastric enetric plexus)

2. Acid in the stomach

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100
Q

What does ECL cells stand for?

A

Enterochromaffin-Like cell (ECL cell)

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101
Q

Which cell type does the parietal cells in the gastric glands work closely with?

A

ECL cells

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102
Q

What do the ECL cells secrete that results in the parietal cells secreting HCl and what controls this process?

A

Rate and amount of HCL produced is directly related to histamine from ECL cells, which is controlled by GASTRIN

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103
Q

Which cells make gastrin?

A

G cells in the pyloric glands in the distal end of the stomach

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104
Q

When the G cells in the pyloric glands sense that there is a protein rich meal what occurs?

A

G cells are stimulated by protein to release GASTRIN into the blood to reach the ECL cells, which when stimulated by gastrin will release HISTAMINE which results in HCL release from the parietal cells

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105
Q

Which secretagogue is the most important in gastric acid secretion?

A

Histamine!

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106
Q

What are the 3 phases of gastric secretion and how much do they account for acid secretion?

A
  1. Cephalic Phase = 30% acid production
  2. Gastric Phase = 60% acid production
  3. Intestinal Phase = 10% acid production
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107
Q

What controls the cephalic phase of gastric secretion?

A

Sight, smell, taste of food → HCl + pepsin release
Controlled by:
Cerebral cortex (appetite center amygdala and hypothalamus) → Vagus n. → Stomach via Acetylchoine
G cells →Gastrin Releasing peptide = GASTRIN release

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108
Q

What controls the gastric phase of gastric secretion?

A 
Food in stomach (stretch) = HCl release
Controlled by:
Long vagovagal reflex = acetylcholine
Local enteric reflex 
Peptides and AA → G cells → GASTRIN
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109
Q

What controls the intestinal phase of gastric secretion?

A

Food in duodenum
Controlled by:
Enterooxyntic (not gastrin per CVT??)

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110
Q

How is gastric secretion inhibited?

A

Food in SI

  1. Reverse enterogastric reflex (myeneteric NS, sympathetic NS, vagus n)
  2. Food in SI stimulates secretion of SECRETIN and 3 other inhibitors (gastric inhibitory peptide, somatostatin, vasoactive intestinal peptide)
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111
Q

What happens in the stomach glands between meals?

A

They make mucus, almost NO acid!

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112
Q

What is the pancreatic duct and which species have it?

A

Opens within bile duct at major duodenal papilla
Dogs = Usually (smaller, but can be absent)
Cats = ALWAYS!

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113
Q

What is the accessory pancreatic duct and which species have it?

A

Opens into duodenum at minor duodenal papilla
Dogs = ALWAYS!
Cats = Occasionally

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114
Q

What are the two main functions of pancreatic secretions?

A
  1. Digestive enzymes

2. Na bicarbonate

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115
Q

How are pancreatic enzymes secreted?

A

Pancreatic enzymes are secreted as zymogens (INACTIVE form) - Such as trypsinogen
Once into the small intestine they are activated = Trypsin

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116
Q

Which pancreatic enzyme can activate all the other pancreatic enzymes?

A

Trypsin

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117
Q

What 3 pancreatic enzymes are responsible for protein digestion?

A
  1. Trypsin!!!!
  2. Chymotrypsin
  3. Carboxypolypeptide (can release AA)
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118
Q

What pancreatic enzyme is responsible for carbohydrate digestion?

A

Pancreatic amylase (starch into disaccharides and trisaccharides)

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119
Q

What 3 pancreatic enzymes are responsible for fat digestion?

A 
Pancreatic lipase (fat into FA and monglycerides)
Cholesterol esterase (hydrolysis of cholesterol)
Phospholipase (FA splits from phospholipids)
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120
Q

What enzyme is made in pancreatic acini that helps to prevent autodigestions and were is it present?

A

Trypsin Inhibitor

Prevents activation of zymogens in pancreas or ducts or intracellular

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121
Q

Which cells in the pancreas make bicarbonate?

A

Epithelial cells that line the ductules and ducts

Role of bicarbonate is to neutralize acid from stomach chyme

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122
Q

What are the steps in making bicarbonate in the pancreas?

A
  1. CO2 diffuses into the cell from the blood, combines with water to form carbonic acid (H2CO3), dissociates into H+ and HCO3-
  2. H+ is traded in the blood for Na+, which is transported out of the cell with HCO3-
  3. This also pulls water by osmosis
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123
Q

What are the 3 main stimuli for pancreatic secretion?

A
  1. Acetylcholine
  2. Cholecystokinin (CCK)
  3. Secretin
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124
Q

Which hormones control release of pancreatic fluid and bicarbonate?

A

Secretin

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125
Q

Which hormones control release of pancreatic digestive enzymes?

A 
Vagal stimulation (acetylcholine)
Cholecystokinin (CCK)
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126
Q

What stimulates the release of acetylcholine that results in pancreatic secretions?

A

Vagus n. and ENS stimulation

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127
Q

What stimulates the release of cholecytskinin (CCK) that results in pancreatic secretions?

A

Released from duodenum and upper jejunum from I cells in response to protein or AA in the lumen

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128
Q

What stimulates the release of secretin that results in pancreatic secretions?

A

Released from duodenum and jejunum in response to acidic content of chyme in the lumen

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129
Q

What is important about the 3 stimuli that result in pancreatic secretions?

A

The stimuli potentate each other, meaning that pancreatic secretion is greatest with the combined stimuli as compared to single stimuli

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130
Q

What are the 3 phases of pancreatic secretion?

A

Same as gastric secretion

  1. Cephalic = 20% pancreatic enzymes
  2. Gastric = 5-10% pancreatic enzymes
  3. Intestinal: LOTS of pancreatic fluid and bicarbonate (secretin); 70-80% pancreatic enzymes (CCK)
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131
Q

What controls the cephalic phase of pancreatic secretion?

A

Acetylcholine (vagal n.) = 20% pancreatic enzymes (BUT NO fluid)

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132
Q

What controls the gastric phase of pancreatic secretion?

A

Acetylcholine (vagal n.) = 5-10% pancreatic enzymes (BUT NO fluid)

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133
Q

What controls the intestinal phase of pancreatic secretion?

A
  1. Chyme in SI (acid) → Secretin (from S cells in duodenum) → Lots of pancreatic fluid and bicarbonate
  2. Food in SI (peptides/fat) → CCK (from I cells in duodenum and upper jejunum) → 70-80% pancreatic enzymes
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134
Q

What are the two main roles of bile?

A
  1. Fat digestion and absorption (based on bile acids/salts that aid in emulsifying and absorbing fats)
  2. Excretion of waste (including bilirubin and cholesterol)
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135
Q

What are the two stages of bile secretion?

A
  1. Bile is secreted by hepatocytes into bile canaliculi
  2. Bile flows through ducts to the hepatic duct → common bile duct → duodenum OR cystic duct to Gallbladder
    Along the way in the ductules/ducts watery Na+ and HCO3- solution secreted by secretory epithelial cells (stimulated by secretin)
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136
Q

Which hormones results in secretion of watery Na+ and HCO3- solution from secretory epithelial cells during the second stage of bile secretion?

A

Secretin!! Which is stimulated by presence of acid within the duodenum

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137
Q

What happens to bile when it is stored in the GB?

A

The bile is concentrated (Water, Na+, Cl- are absorbed through the wall of the GB) - via active transport of Na+ and passive movement of others = Concentration of bile salts, cholesterol. Lecithin, bilirubin

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138
Q

What are the two imperative steps in emptying the GB and what controls this?

A

Need contraction of GB and relaxation of Sphincter of Oddi (at exit of common bile duct into duodenum)
This is stimulated by CCK that is released in response to a fatty meal in the duodenum

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139
Q

How are bile salts made?

A

From cholesterol (diet or made in liver) → 1. cholic acid OR 2. Chenodeoxycholic acid → These combine with either 1. Glycine or 2. Taurine → Conjugated bile salts

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140
Q

What are the two main roles of bile salts?

A
  1. Emulsifying or detergent function (decrease surface tension, allows GIT to break down fats)
  2. Absorption of micelles into blood (MAJOR effect! = fatty acids, monoglycerides, cholesterol, other lipids)
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141
Q

What 4 components are absorbed via micelles with bile salts?

A
  1. Fatty Acids
  2. Monglycerides
  3. Cholesterol
  4. Other Lipids
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142
Q

Explain enterohepatic circulation of bile salts?

A

Bile salts are reabsorbed in SI (diffusion and active transport) → Portal blood → Liver venous sinusoids → Hepatocytes → Bile
About 94% of bile salts are recirculated (up to 17x)

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143
Q

What are the 2 main glands in the SI that result in secretions?

A
  1. Brunner’s glands = Mucus and bicarbonate

2. Crypts of Lieberkuhn = Digestive Juices (mucus and watery vehicle)

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144
Q

What are the Brunner’s gland stimulated by in the SI?

A

Result in mucus and bicarbonate secretion
Stimulated by: food, vagal stimulation, secretin
Result in protection of mucosa in duodenum

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145
Q

What are the two main cells types of the Crypts of Lieberkuhn?

A
  1. Goblet Cells = Mucus

2. Enterocytes = Absorb and secrete water and electrolytes (PURE ECF, alkaline fluid)

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146
Q

How dot he enterocytes of the Crypts of Lieberkuhn result in formation of a watery vehicle?

A
  1. Active secretion of Cl-
  2. Active secretion of HCO3-
    Drags along Na+ and water
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147
Q

What are the main villus enzymes?

A
  1. Peptidase (peptides → AA)
  2. Sucrase, maltase, isomaltase, lactase (dissaccharides → monosaccharides)
  3. Intestinal lipase (fats → glycerol and FA)
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148
Q

Does the large intestinal have villi and Crypts of Lieberkuhn?

A

No villi

Yes - Crypts of Lieberkuhn

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149
Q

What is the major component of the Crypts of Lieberkuhn in the large intestine?

A

MUCUS (some bicarbonate) - Lubrication and hold feces together

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150
Q

Why is saliva hypotonic?

A

Active net solute absorption and salivary ducts are impermeable to water

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151
Q

Why is neural stimulation of the salivary glands unique?

A

They are controlled by both parasympathetic and sympathetic NS

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152
Q

What are the net results of gastric parietal cells?

A

Net secretion of HCl and net absorption of HCO3- (alkalaine tide that is seen after meals)

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153
Q

What are the 3 main stimulators of H+ secretion on parietal cells and what are their receptors?

A
  1. ACh (From Vagus n, M3 receptor)
  2. Gastrin (From G cells in antrum, CCKb receptor)
  3. Histamine (From ECL cells, H2 receptor)
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154
Q

What is the MOA of PPI, omeprazole?

A

Inhibit the H+/K+ ATPase on the apical membrane of the gastric parietal cell

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155
Q

Name the 2 primary bile acids.

A

Cholic acid and chenodeoxycholic acid

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156
Q

Name 2 enzymes that aid in starch digestion that are not found in intestinal epithelium.

A
  1. Salivary alpha amylase (Ptyalin)

2. Pancreatic amylase

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157
Q

What enzymes and where are disacchardies hydrolyzed into monosaccharides?

A

Intestinal Epithelial Enzymes - Within villi in the brush border

  1. Maltase
  2. Alpha-Dextrinase
  3. Lactase
  4. Sucrase
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158
Q

What does lactase do?

A

Splits Lactose into galactose and glucose

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159
Q

What does sucrose do?

A

Splits sucrose into fructose and glucose

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160
Q

What does maltose and other 3-9 glucose polymers split into?

A

Glucose by maltase and alpha-dextinase

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161
Q

What are the final products of carbodyhrate digestion?

A

Monosaccarides that are absorbed immediately into portal blood

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162
Q

What 3 locations do carbohydrate digestion occur?

A
  1. Mouth
  2. Small intestine (pancreatic secretions)
  3. Villi (Brush border)
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163
Q

What is the most important function of pepsin?

A

Digestion of collagen (to allow digestion of other cellular proteins)

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164
Q

Name 3 places that protein digestion occurs?

A
  1. Stomach
  2. Duodenum/Upper jejunum (pancreatic secretions)
  3. Enterocytes (duodenum and jejunum)
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165
Q

What is the final product of protein digestion?

A

Amino Acids

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166
Q

What is the enzyme in the stomach that aid in protein digestion?

A

Pepsin

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167
Q

What are the enzymes in the duodenum/upper jejenum that aid in protein digestion?

A

Pancreatic enzymes: Trypsin. Chymotrypsin, carboxypolypeptidase, proelastase

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168
Q

What is the enzyme in the enterocytes that aids in final polypeptide and amino acid digestion?

A

Peptidases (aminopolypeptidase, dipeptidase)

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169
Q

What is the most important enzyme of fat digestion?

A

Pancreatic lipase (little by enteric lipase)

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170
Q

What is the final product of fat digestion?

A

Fatty acids and 2-monoglycerides

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171
Q

What are essential for emulsification of tryglycerides?

A

Bile salts and lecithin

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172
Q

By what process is water absorbed in the small intestine?

A

Entirely by diffusion

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173
Q

What is the main mechanism of ion absorption in SI?

A

Active transport of Na+
Na+ is actively transported from basolateral membrane into interstitial space Low intracellular conc of Na → electrochemical gradient → therefore more Na moves from chyme into enterocyte

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174
Q

What are the 3 final monosaccharides?

A
  1. Glucose
  2. Galatose
  3. Fructose
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175
Q

What is another name for the Na+/glucose cotransporter in the SI?

A

SGLT 1

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176
Q

Which transporter is located on the basolateral surface to transport glucose, galactose, and fructose into the blood?

A

GLUT 2

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177
Q

Which transporter on the apical surface allows for facilitated diffusion of fructose?

A

GLUT 5

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178
Q

Which enzyme in the brush border in the SI converts trypsinogen into trypsin?

A

Enterokinase

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179
Q

What are the 2 main ways that proteins are absorbed in the SI?

A

Via Na+ co-transporter or less by facilitated diffusion

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180
Q

Name the 4 fat soluble vitamins.

A

Vitamins A, D, E, K

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181
Q

What are the 4 steps of Vitamin B12 absorption?

A
  1. Dietary B12 released from pepsin (stomach)
  2. Free B12 binds to R protein (from saliva)
  3. Duodenum: Pancreatic proteases degrade R protein and Vit B12 transferred to intrinsic factor (prevented from degrading)
  4. Vit B12-Intrinsic Factor Complex - Ileum it is transported
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182
Q

What is the major site of Na+ absorption in the SI?

A

Jejunum

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183
Q

What occurs in the colonocytes for Na and K?

A

Na+ absorption (+++aldosterone)

K+ secretion

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184
Q

What are 2 main things that are lost in diarrhea?

A

HCO3- and K+ = Hypercholermic metabolic acidosis

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185
Q

What is the main electrolyte that is secreted by enterocytes?

A

Cl- (based on increased cAMP). Na+ and water follow = secretion

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186
Q

What are the 2 main blood supplies for the liver?

A

Portal vein and hepatic artery

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187
Q

What accounts for the huge regenerative capacity of the liver?

A

HGF (Heptocyte growth factor) produced by mesenchymal cells

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188
Q

What is the name of the reticuloendothelial cells in the liver?

A

Kupffer cells

189
Q

What are the 3 things in the portal triad?

A
  1. Portal Vein
  2. Bile Duct
  3. Hepatic Artery
190
Q

What are the areas that lymph is created/filtrated in the liver lobules?

A

Within the Space of Disse

191
Q

What are the 4 main functions of the liver in carbohydrate metabolism?

A
  1. Store glycogen (glucose buffer)
  2. Convert galactose/fructose into glucose
  3. Gluconeogenesis
192
Q

What are the 3 main functions of the liver in fat metabolism.

A
  1. High rate of oxidation of fatty acids (fats → glycerol + FFA → Beta oxidation →Acetyl CoA→TCA Cycle or acretoacetic acid
  2. Synthesis cholesterol (for bile salts), phospholipids (cell membranes), lipoproteins
  3. Convert carbs and proteins into fat
193
Q

What are the 4 main functions of the liver in protein metabolism?

A
  1. Deamination of AA
  2. Formation of urea
  3. Formation of plasma proteins (except Ig)
  4. Interconversion of AA
194
Q

Name 4 other functions of the liver in metabolism.

A
  1. Stores Vitamins - A, D, B12
  2. Blood coagulation - makes factors (needs Vit K)
  3. Storage of iron == Ferritin
  4. Metabolizes drugs, hormones, Ca2+, others
195
Q

Discuss the excretion of bilirubin.

A
  1. RBCs are degraded by reticuloendothelial system (heme + globin)
  2. Via heme oxygenase = Biliverdin
  3. Unconjugated bilirbin (bound to albumin)
  4. In liver conguates with glucuronic acid = Bilirubin glucuronide (80%) and bilirbuin sulfate (10%) = Conjugated bilirubin
  5. Conjugated bilirubin is excreted in bile into intestesines
  6. In intestines - intestinal bacteria convert it into urobilinogen
  7. About 90% of urobilinogen is converted to stercobilinogen then converted to stercobilin and is excreted in feces
  8. About 10% of urobilinogen is absorbed into blood and is either recycled to bile (about 95%) or excreted by kidney (about 5%). When urobilinogen is exposure to air in the urine it is converted to urobilin
196
Q

What would you expect with bilirubin in hemolysis?

A

Unconjugated bilirubin high

197
Q

What would you expect with bilirubin in Cholestasis?

A

Conjugated bilirubin high

198
Q

What would you expect with bilirubin in total EHBDO?

A

NO bilirbin in feces (since no stercobilin stool is light), no urobilin in urine

199
Q

How is urea formed in the urine?

A

Amino Acid + Keto acid (alpha keto-glutoric acid) gets transminated into keto acid + amino acid (glutamic acid)
Via oxiative deamination glutamic acid is converted to keto acid + NH3 (ammonia)
The ammonia combined with CO2 and creates urea!

200
Q

Which cell in the stomach makes intrinsic factor?

A

Parietal cells

201
Q

What are the 3 major components of acid secretion?

A

Histamine, Gastrin, ACh

202
Q

Which hormone is responsible for decreasing gastrin, histamine, and acid secretion when stomach pH

A

Somatostatin

203
Q

What are the components of the gastric mucosal barrier?

A 
§ Tightly opposed epithelial cells
				§ Bicarbonate rich mucous
				§ Abundant mucosal blood supply
				§ Prostaglandins (PGE2) are important in modulating
					· Blood flow
					· Bicarbonate secretion
					· Epithelial cell renewal
204
Q

What factors slow emptying of stomach?

A

Carbs, AA, fats

Release of CCK in response to FA and AA

205
Q

What are the 3 major digestive enzymes in the stomach?

A 
Pepsin (releases as pepsinogen in response to ACh and histamine)
Gastric lipase (in response to pentagastrin, histamine, PGE2, and secretin, active in SI)
Intrinsic factor (dogs)
206
Q

Which breeds get hypertrophic gastropathy?

A

Basenji, small breed dogs (shih Tzu)

207
Q

Which breed gets atophic gastritis?

A

Lundehund

208
Q

What can stoamtocytosis tell you on a CBC?

A

Stomatocytosis has been described in Drentse Patrijshond dogs with familial stomatocytosis-hypertrophic gastritis

209
Q

What are causes of metabolic alkalosis?

A

· Metabolic alkalosis
o Associated with pyloric/duodenal outflow obstruction
o Associated with parvo and pancreatitis
o Gastrinomas
§ Also associated with aciduria
§ hypoCl/K due to gastric acid hypersecretion

Conservation of volume at expense of pH (renal reabsorb HCO3 and exchange Na for H+ = promotes acidic urine (paradoxical aciduria)

210
Q

What breed when given IV secretin will have a high gastrin level w/o a gastrinoma?

A

Basenjis (with enteropathies)

211
Q

What gastric tumors are found in these locations? Pyloric antrum, cardia, diffuse

A 
§ Pyloric antrum
					· Adenocarcinoma (lesser curvature also)
				§ Cardia
					· Leiomyoma
				§ Diffuse
					· LSA
212
Q

What is the most common site of an adenomatous polyp?

A

Pyloric antrum

213
Q

Which breeds are predisposed to PLE?

A

SCWT, Yorkie, Basenji, Lundehund, Shar-Pei

214
Q

What AA def can results in high ammonia in cats?

A

Arginine def

215
Q

Which coag factor is NOT made by the liver?

A

Factor VIII

216
Q

What defines DIC?

A 
Prolonged PT/PTT
Decreases fibrinogen
thrombocytopenia
increased FDPs
(all of which can be seen with liver dz too)
217
Q

What is the most toxic bile acid?

A

Lithocholic acid

218
Q

How can diuretics exacerbate HE?

A

Alkalosis and HypoK!!!

219
Q

What tropic factors are important for hepatic growth?

A

Insulin and Glucagon (from portal blood)

220
Q

What is the toxin in cycad?

A

Cycasin (converted to MAM (methylazoxymethanol) by GI microbes) and unnamed neuro toxin

221
Q

What is the MOA of cycad toxin?

A

Cycasin: MAM results in GI, hepatotoxin, neurotoxin

MAM alkylates DNA/RNA

222
Q

What are the target organs of cycad toxin?

A

Cycasin: LIVER, GI, Neuro

223
Q

What is the clinical presentation of cycad toxin?

A

Cycasin: within 24 hrs (GI signs and neuro signs)

224
Q

What are the main clin path signs of cycad toxin?

A

50-60% increased transaminases
30-50% increased bili
50% increased PT/PTT
30% decreased platelets

225
Q

What are the histopath features of cycad toxin?

A

Cycasin: MIXED
Acute: Centrilobular necrosis and neutrophilic inflammation
Chronic: LP inflammation, fibrosis, biliary hyperplasia

226
Q

What is the definitive test for cycad toxin?

A

None, hx of eating plant = Look for plant in vomit

227
Q

What antidotes are recommended for cycad toxin?

A

Charcoal! Shown to be protective!!!!

228
Q

What is the prognosis for cycad toxin?

A

Cycasin: Guarded - 30-50% mortality

229
Q

What are the known prognostic indicators for cycad toxin?

A

Higher ALT, T bili, lower albumin (at presentation), prolonged coag = NONSURVIVORS

Early charcoal admin was PROTECTIVE!!

230
Q

What is the toxin in amanita?

A

Alpha-amanitin (1 cap can kill!)

231
Q

What is the MOA of amanita?

A

Alpha-amanitin: Inhibits RNA polymerase II (no transcription or protein synthesis)

Apoptosis of hepatocytes

Insulin Release

232
Q

What are the target tissues of amanita?

A

LIVER
Intestines (crypts)
Kidneys (prox tubules)

233
Q

What is the onset of CS with amanita?

A

GI phase: 6-12 hrs - Severe gastroenteritis
Recovery: 12-24 hrs
HEPATIC FAILURE: 36-48 hrs
Fulminate liver and kidney failure

234
Q

What are the clin path changes with amanita?

A

Hypoglycemia (releases insulin)
Coagulopathy
Azotemia
Increased AST, ALT, ALP, bili

235
Q

What are the histopath findings with amanita?

A

Pan-lobular hepatocellular necrosis

Acute tubular necrosis

236
Q

How do you make a definitive diagnosis of amanita?

A

LC/MS or ELISA for alpha-amanitin (toxin)
Early in urine or in vomit (also see mushrooms)
Later kidney or liver

237
Q

What is the antidote for amanita?

A

Silibinin has helped!!!

Charcoal (if early)

238
Q

What is the prognosis for amanita in dogs?

A

Poor

50% mortality in dogs

239
Q

What is the toxin in cyanobacteria?

A

Microcysts aeruginosa (blue green algae) = Microcystins

240
Q

What is the MOA in cyanobacteria toxin?

A

Microcystins: Inhibit serine-threonine phosphatases = Build up of phosphorylated proteins = Necrosis = Apoptosis = Massive HEMORRHAGE

241
Q

What are the target organs of cyanobacteria?

A

Microcystins: Liver, Kidney (prox tub) and Neuro (anabaena)

242
Q

What is the presentations of cyanobacteria?

A

Microcystins: ACUTE (hours) - GI, respiratory, liver, tremors, seizures, comas

243
Q

What are the clin path findings with cyanobacteria?

A

Increased ALP, GGT, bili

Marked increased in ALT (can be less if microcystoin inhibits tansminase synthesis??)

244
Q

What is the histopath finding for cyanobacteria?

A

Hepatic necrosis - MASSIVE hemorrhage

Acute renal tubular necrosis

245
Q

How is a definitive diagnosis of cyanobacteria made?

A

ELISA (confirmed with LC/MS) or MMPB method to detect all forms of toxin)
Best in vomit!!!, can check water source too
Liver (toxin level)

246
Q

What is the antidote for cyanobacteria?

A

NONE

Rifampin in mice/rats can inhibit uptake

247
Q

What is the prognosis for cyanobacteria?

A

GRAVE

248
Q

What is the toxin with aflatoxin?

A

Aspergillus = Aflatoxin B1 converted to AFB1 8,9 epoxide

esp dogs and poultry

249
Q

What is the MOA of aflatoxin?

A

P450 converts to AFB1 8,9 epoxide
Inhibits RNA polymerase
Bind to mitochondrial DNA
Depletes GSH

250
Q

What are the target tissues of aflatoxin?

A

Liver

Kidney (prox tubules) - CASTS before azotemia

251
Q

What is the CS onset of aflatoxin?

A

Highly variable, most are chronic (>1 month of eating food)

252
Q

What are the clin path findings with aflatoxin?

A

Increased LEs, icterus, low cholesterol, decreased AT and protein C

253
Q

What are the histopath findings with aflatoxin?

A

Acute: Centrilobular necrosis Diffuse hepatocyte lipid vacuolization
Chronic: MIXED

254
Q

How do you make a definitive diagnosis of aflatoxin?

A

ELISA, HPLC, LC/MS for toxin AFB1 in food source (>60 ppb)

Serum, liver, urine = Alfatoxin M1

255
Q

What is the antidote for aflatoxin?

A 
Replenish GSH (N-acetylcysteine or SAMe)
Sulfhydryl groups may bind AFB1 8,9 epoxide too
256
Q

What is the prognosis for aflatoxin?

A

Guarded, 60% mortality

257
Q

What are the prognostic indicators for aflatoxin?

A

100% predictive of death = CASTS
Longer PT/PTT, decreased AT, decreased protein C, increased bili, decreased albumin and cholesterol = Risk factors for mortality

258
Q

What is the MOA of xylitol?

A

Rapid, severe increased in insulin from Beta cells (6X more than glucose)!!

Hepatic depletion of ALP (from metabolism via pentose phosphate pathway)

259
Q

What are the target organs of xylitol?

A 
LIVER (>0.5 g/kg)
Beta cells (>0.1 g/kg)
260
Q

What are the clinical presentation with xylitol?

A

30 min-1 hrs - Hypoglycemia

9-72 hrs = Acute hepatic failure

261
Q

What are the clin path findings with xylitol?

A

Marked increased ALT, bili
Hypoglycemia
Coagulopathy
HypoK, HypoPhos

262
Q

What is the histopath findings with xylitol?

A

Periacinar-mid zonal necrosis

263
Q

What is the definitive diagnosis of xylitol?

A

HX, no tests for it

264
Q

What is the antidote for xylitol?

A

Early emesis, SAMe, dextrose

Charcoal DOES NOT bind it

265
Q

What is the prognosis for xylitol?

A

Good if early, guarded if prolonged hypoglycemia and LEs increased

266
Q

What is a prognostic indicator for xylitol?

A

Hyperphosphatemia - Poor prognosis

267
Q

What is the MOA of carprofen?

A

Idiosyncratic cytotoxic hepatocellular reaction (maybe IM) - Labs?

268
Q

What are the target organs for carprofen?

A

LIVER, kidney, GIT

269
Q

What breed is susceptible to carprofen tox?

A

Labs

270
Q

What is the onset of carprofen tox?

A

VARIABLE - 5-30 days (longer onset in labs)

271
Q

What are the clin findings in carprofen tox?

A

Increased ALT and bili

2/3 = Proteinuria, glucouria, and granular casts!!!

272
Q

What is the histopath of carprofen tox?

A

MIXED (necrosis and inflammation)

273
Q

What is the antidote for carprofen tox?

A

STOP carprofen!!

274
Q

What is the prognosis for carprofen tox?

A

Good, 100% labs recover

Only 50% in other breeds

275
Q

Does the dose and duration of carprofen predict the prognosis?

A

NO!!

276
Q

What is the toxin in diazepam?

A

Oral dosing in cats - converted to “reactive metabolite” of unknown structure = Idiosyncratic

277
Q

What is the target tissue for oral diazepam in cats?

A

LIVER

278
Q

What is the onset of CS in diazepam liver failure in cats?

A

Within first 7 days after oral dosing

279
Q

What are the clin path findings with diazepam in cats?

A

Relative decrease in glucose, marked increase ALT»»»ALP, prolonged PT/PTT
Increased CK

280
Q

What is the histopath with oral diazepam in cats?

A

Centrilobular necrosis (MASSIVE!)

281
Q

What is the antidote for oral diazepam in cats?

A

STOP diazepam

Silymarin within 24 hrs, SAMe and N-Acetylcystein worked in one cat

282
Q

What is the prognosis for oral diazepam liver failure in cats?

A

GRAVE - MOST died within 1-5 days of onset of CS!!!!

283
Q

What are two complications of gastrinomas?

A

Acid hypersecretion = GI bleeding

Gastric mucosal hyperplasia - Outflow obstructions

284
Q

What are the stimulation test for gastrinomas?

A

Secretin stimulation and Ca stimulation to increased gastrin

285
Q

What are the tx for gastrinomas?

A
  1. Sx
  2. Octerotide
  3. Antacids
286
Q

What are risk factors for pancreatitis?

A
  1. Dietary indiscretion (high fat)
  2. Hyperlipidemia (Min Schnauzer)
  3. Hereditary (SPINK1 Mini Schnauzer)
  4. Drugs (azathioprine, KBR, vincristine)
  5. HyperCa
  6. Endocrine dz (HypoT4, HAC, DM - weak associations)
  7. Sx manipulation and trauma
  8. Infections (B. canis rossi)
  9. Autoimmune
  10. Neoplasia
287
Q

Can steroids result in pancreatitis?

A

NO! Can increased lipase (some dogs) w/o pncreatitis

288
Q

What are the 4 safegaurds within pancreas?

A
  1. Zymogens (inactive)
  2. Zymogens granules are separate from lysosomes (physically)
  3. Pancreatic Secretory Trypsin Inhibitor (PSTI) - immediate inhibition of trypsin
  4. Larger antiproteases in circulation (alpha 2 macroglobulin)
289
Q

What is the process of acute pancreatitis?

A
  1. Apical Block: Zymogens are not secreted
  2. Colocalization of zymogens and proteases (overwhelm pancreatitic secretory trypsin inhibitor = Phospholipase A2, elastase, chymotryspin, lipase)
  3. Recruitment of neutrophils and ROS production
  4. Change in pancreatic circulation = vasconstriction
  5. Activation of complement and change in permeability
  6. Cytokine Storm!!!
    End result = Massive inflammation
290
Q

What % of dogs with pancreatitis have amylase and lipase within RR?

A

About 50%

Can be increased in 50% dogs that do NOT have pancreatitis too

291
Q

What is the most sensitive and specific test for pancreatitis?

A

cPLI
Spec cPL
SNAP cPL (good to exclude pancreatitis, so if normal NOT pancreatitis; abnormal SNAP may not be pancreatisi check Spec cPL)

292
Q

What are potential complications with pancreatitis?

A

Pancreatitic cytokines = Systemic effects

  1. AKI
  2. DIC
  3. Cardiac arrhythmias
  4. ALI (neutrophilic inflammation)
  5. EPI
  6. Pseudocytes
  7. Pancreatitic encephalopathy (dog)
  8. MODS
  9. SIRS
  10. Chronic relapsing pancreatitis
293
Q

What is the principle behind use of plasma in pancreatitis cases?

A

More alpha 2 macrolobulin (protease) BUT there is no proof in vet med that it is of benefit

294
Q

What protease inhibitor has shown some benefit in pancreatitis?

A

Aprotinin

295
Q

Which anti-emetic may be benefit in pancreatitis since inflammed pancreas can secrete substance P?

A

Maropitant

296
Q

Is there a benefit of ABX with pancreatitis?

A

None seen with cochrane review

297
Q

What are tx for chronic pancreatitis?

A 
Seen in Mini Schanzuers
Spec cPL >400 + waxing adn waning CS (every few days)
Ultra low fat diet (RC GI low fat)
Hypoallergenic diet
Prednisone (14 days with taper)
Cyclosporine
298
Q

Why should you not used TLI to dx pancreasitis?

A

Lacks sens for pancreatitis

Can increased with renal failure!

299
Q

What are not useful tests to dx pancreatitis?

A 
Amylase/Lipase
Trypsinogen Activation Peptide (TAP)
Trypsin alpha1 proteinase inhibitor
Alpha 2 macroglobulin
CRP
300
Q

How long can the PLI remain elevated after pancreatitis?

A

10-12 days

301
Q

Can PLI predict severity on histopath of pancreatitis?

A

NO!

302
Q

What are the ranges of PLI for pancreatitis?

A

DOGS >400

CATS >5.4

303
Q

Is the PLI affected by renal failure?

A

NO!

But TLI is affected by renal failure

304
Q

What are the two main forms of EPI?

A 
Acinar atropy (GSD, collies) - Endocrine functional
Chronic pancreatits = Atrophy and fibrosis (all parts of endocrine lacking too)
305
Q

Which single pancreatic enzyme def has been reported in dogs?

A

Lack of pancreatic lipase (will have normal TLI, but CS of EPI)

306
Q

Are there markers of progression in EPI?

A

NO! Can be subclinical for years

Early immunosuppression is NOT recommended

307
Q

What is the diagnostics of choice for EPI?

A

TLI Low

308
Q

Can fecal pancreatitic elastase be used to dx EPI?

A

Yes, but need to verify with cTLI

Since false + 23% (low elastase and normal cTLI)

309
Q

What % EPI dogs have Vit B 12 def?

A

About 82%

310
Q

What is a potential complication of EPI?

A

Mesentric torsion!

311
Q

What is associated with a shorter survival in EPI dogs?

A

Concurrent Vit B12 defs (need to check B12 in every patient with EPI)

312
Q

What % EPI dogs have poor response?

A

About 20%

313
Q

What are potential reasons for treatment failure in EPI dogs?

A
  1. IBD, DM, SIBO - Need to tx

2. Need PPI - To prevent pancreatic enzymes from being destroyed

314
Q

What is a complication with pancreatitic extract in EPI dogs?

A

Oral bleeding (need to reduce dose and wet it)

315
Q

Why can GI disease result in high false + fecal pancreatitic elastase-1?

A

Due to high neutrophil elastase

316
Q

What are 3 reasons to have a normal TLI with EPI?

A
  1. Pancreatic duct obstruction
  2. Congenital def intestinal enteropeptidase
  3. Selective pancreatic enzyme def (NOT trypsin)
317
Q

Is EPI inherited in GSD?

A

Based on test mating - NO!

318
Q

What are 6 options for pancreatic dz in cats?

A
  1. Acute necrotizing panceratitis
  2. Acute suupurative panc (Neutrophils = Younger cats)
  3. Chronic panc (lymphocytic inflammation and fibrosis)
  4. Panc Neoplasia (adenocarc - ductal)
  5. Pancreatic Nodular Hyperplasia (unknown significance)
  6. EPI?? (mainly from chronic panc, can occur with flukes too - Eurytrema procyonis)
319
Q

What are risk factors for panc in cats?

A
  1. Concurrent biliary dz (cholangitis)
  2. Concurrent GI disease (IBD) - Direct communication from bile duct to pancreatic duct - Reflux
  3. Ischemia
  4. Infeciton (toxo, FHV-1, FIP, Eurytrema, Amphimerus, virulent calici)
  5. Pancreatic Obstructions (neoplasia, fluke, stone)
  6. Trauma (high rise)
  7. Organophosphates
  8. Lipodystrophy
  9. HyperCa (exp)
  10. Nutrition = UNDERWEIGHT cats
320
Q

What is a common electrolyte abnormality in cats with AP?

A

HypoCa - 65% - Worse prognosis (more common than in dogs)

321
Q

What are 4 complications of AP in cats?

A
  1. Chronic panc
  2. EPI
  3. Hepatic Lipidosis *even worse if together
  4. DM
322
Q

Why are H2 and H1 blockers recommended in feline panc?

A

Histamine and bradykinin induced vascular permeability can be blocked to prevent hemorrhage and necrosis

323
Q

Which test has been validated in cats for AP?

A

fPLI

324
Q

What are pulmonary manifestations of GERD?

A

From chronic microaspiration events

  1. Aspiration pneumonia
  2. Chronic Bronchitis
  3. Interstitial Pulmonary Fibrosis
325
Q

What is the tx for Spirocerca?

A

Doramectin

326
Q

What are the 3 defensive lines to prevent epithelial damage?

A
  1. Mucus and Bicarbonate Barrier
  2. Epithelial cell mechanisms; barrier function of apical plasma membrane, intrinsic cell defenses
  3. Blood flow mediated removal of back diffused H and energy supply
    If all FAIL = Epithelial Cell Injury!!
327
Q

What are the effects of NSAIDs on mucosa?

A
  1. Direct effect (uncoupling mitochondria)
  2. COX 1 inhibition: Neutrophil activation and ROS
  3. COX 2 inhibition: Neutrophil activation and ROS; Also inhibits GF production and impairs repair
328
Q

What is the stomach worm in cats?

A

Ollulanus tricuspids
Ingesting cat vomit
Tx: Fenbendazole

329
Q

What is a stomach worm in dogs/cats? Where is it from?

A

Physalloptera; Ingestion of cockroach/beetle (IH) or lizards

Tx: Pyrantel

330
Q

What is the recommend tx for Helicobacter?

A

Amoxicillin, Clarithromycin, and omeprazole for 3 weeks

331
Q

What is the tx for Campylobacter?

A

Fluoroquinolones

332
Q

Which hookworm can result in pedal pruritus in greyhounds?

A

Uncinaria stenocephala

333
Q

What is a treatment for round worms?

A

Fenbendazole

334
Q

What is a tx for hookworms?

A

Pyrantel

335
Q

What is a tx for tapeworms?

A

Praziquantel and flea control

336
Q

An increase in which TRL is seen with IBD?

A

TLR2

Also 4, 9

337
Q

Does clinical improvement with IBD mean that there is histopath improvement?

A

NO!

338
Q

What are the 5 steps of cobalamin absorption?

A
  1. Cobalamin released from food in stomach
  2. Binds to cobalamin binding protein (Haptocorrin - from salivary and gastric source)
  3. In duodenum: Haptocorrin degraded (by pancreatic proteases) and Cobalamin binds to intrinsic factor (pancreas and stomach in dog and ONLY pancreas in cats)
  4. Cobalamin-IF binds to receptors (cubilin) in microvillus
  5. Cobalamin transcytose portal blood bound to tanscobalamin 2 - mediated absoprtion by target cells

Can undergo enterohepatic recirculation with haptocorrin in bile

339
Q

In which breed can you see Vit 12 def (cubilin defects)?

A

Border Collies
Giant Schnauzer
Beagles
Aust Shap

340
Q

Name several compounds that are associated with hepatic encephalopathy?

A 
Ammonia
Tryptophan
Glutamine
Aromatic AA/Branch Chained AA
SCFA
GABA
Endogenous benzodiazepines
Bile Acids
Phenol
Flase neutrotransmitters
341
Q

What are the proposed mechanisms of how ursodeoxycholic acid works?

A
  1. Replace more hydrophobic hepatotoxic bile acids in circulation
  2. Induced choleresis
  3. Stabilization of mitochondrial function (preventing apoptosis)
  4. Immunomodulation (increased glutathione, decreased Ig from B cells, activate GC receptors)
342
Q

Which breed gets lobular dissecting hepatitis?

A

Standard Poodles

343
Q

Where is copper location in inherited copper storage dz?

A

Centrolobular

344
Q

Where is copper located if you have secondary copper accumulation?

A

Periportal

345
Q

What is the mutation seen in Bedlington terriers with copper hepatopathy?

A

COMMD1 or MURR1

346
Q

What is the tx for copper hepatopathy?

A

Low copper diets

  1. Penicillamine (which increased metallothionein that binds copper) - Trientine is another option
  2. Zinc (increased metallothionein in enterocytes to prevent copper uptake, lost with enterocyte)
347
Q

What is zone 3 necroinflammatory hepatitis?

A

Associated with IBD and see in Maltese
ASCITES!!! Portal Hypertension
Inflammation veno-occlusive dz (lymphs and eosins around hepatic v.)

348
Q

What is noncirrhotic portal hypertension?

A

Portal v hypoplasia with portal hypertension
Seen in Dobies, Rotties, and Cockers
Have abdominal effusion with acquired shunts

349
Q

What is portal v. hypoplasia?

A

MIcroscopic malformation in hepatic microvascular
Thought to nonprogressive
Can be asymptomatic
increased bile acids with normal Protein C, CBC, chem, AUS, scinitgraphy
Can be seen with macroscopic PSS too

350
Q

Why do PSS get microcytosis?

A

iron transport defect

351
Q

What % of shunty dogs can have normal bile acids?

A

21%

352
Q

How can Protein C help with PSS vs Portal v hypoplasia?

A

Low with PSS

Normal (>70%) in MVD

353
Q

Does hepatic bx allow for discrimination btwn PSS and protal v. hypoplasia?

A

NO!

354
Q

How does portal hypertesion lead to ascites?

A

Progressive splanchnic dilation - Peripheral vasodilation
Compensatory hyperdynamic changes (increased CO), compensatory failure, increased circulating volume
RAAS activation and ADH release = Na and Water retenion = Ascites

355
Q

What are precipitating factors of HE?

A

Increased production of ammonia in GIT (high protein meal, GI bleeding)

Increased systemic generation of ammonia (blood transfusion, poor quality protein)

Factors affecting uptake and metabolism of ammonia in CNS (metabolic alkalosis, hypoK, hypoglycemia, inflammation, infections, sedation/anesthesia)

356
Q

What is a major complication of feline PSS correction?

A

75% neurologic complications = Central blindness

357
Q

What is the lesion in neutrophilic cholangitis in cats? Signalment, tx

A

Neutrophils in bile ducts and epithelium
Acute and chronic forms - Ill cats
Associated with pancreatitis, IBD, triaditis
Tx: ABX

358
Q

What is the lesion in lymphcytic cholangitis in cats?

A

Small lymphocytes in portal area, portal fibrosis, biliary duct proliferation
Not always ill but have jaundice, ASCITES, increased globulins
TX: Steroids

359
Q

What is the cat live fluck?

A

Platynosum

Tx: Praziquantel

360
Q

What is lymphocytic portal hepatitis?

A

Nonspecific thought to be an aging change

Older cats

361
Q

What has been identified as a mutation in Shelties with GB mucoceles?

A

ABCB4 transport mutation (phospholipid transporter)

362
Q

Dog with what disease are 29X more likely to develop a GB mucocele?

A

HAC

363
Q

Does biliary rupture and bile peritonitis have prognostic factor?

A

NO!!

364
Q

What is the progression with complete occlusion of the CBD?

A

24 hrs = GB distension
48-72 hrs = Extrahepatic bile duct distension
5-7 days = Intrahepatic ductal dilation

365
Q

What is hepatic lipidosis?

A

Enhanced mobilization of peripheral fat to lover and impaired dissemination of lipid from hepatocytes = Severe hepatic dysfunction

366
Q

Do all cats with HE have increased ammonia?

A

NO!! Ptyalism could be from HE

367
Q

What was associated with worse survival in Hepatic lipidosis?

A

HypoK
Advanced age
Decreased PCV

368
Q

What are the mainstays in Tx of hepatic lipidosis?

A
  1. Feeding!!! High quality protein!!!
  2. B vitamins (B1 and B12)
  3. Fat soluble vits (E and K1)
  4. Amino Acids = L-carnitine and taurine
  5. Antioxidants = SAME and ursodiol
  6. electrolytes: HypoK and HypoMg
369
Q

Which breed gets idiosyncratic hepatotoxicty to sulfas?

A

Dobies!!

370
Q

Zones in the liver & implications?

A

Zone 1: periportal - most prone to toxic injury. Site mainly affected by SECONDARY causes of Cu accumulation.
Zone 2:
Zone 3: centrilobular - most prone to hypoxic injury. Site mainly affected with PRIMARY defects in Cu accumulation.

371
Q

Breeds predisposed to copper storage hepatopathy?

A

Pure + mixed breeds.
Bedlington terriers, Labs, WHWT, Dobermans, Skye terrier, Dalmatians.

372
Q

Copper storage hepatopathy in Bedlington terriers - gene mutation, clinical characteristics?

A

Autosomal recessive disorder.
Deletion of exon 2 of copper metabolism domain containing 1 (COMMD1) gene –> complete absence of protein that normally regulates copper metabolism & homeostasis –> affects biliary copper excretion pathway –> copper accumulation in hepatocellular lysosomes.
Acute form - 2-6yo, hepatomegaly, jaundice, hemolytic anemia. Elevated ALT.
Chronic form - middle-aged and older dogs. Less severe CSx, progressive liver damage.
Dx - liver bx. BUT liver [Cu] does not always correlate with the extent of liver damage & dz progression, also may not ID substantial Cu accumulation in hepatocytes in early dz.

373
Q

Copper metabolism pathway and transporter genes involved?

A

Copper homeostasis relies on regulation of uptake of copper in
the small intestine, cellular metabolism executed by a variety of copper transporters and chaperones, as well as excretion of excessive copper via the biliary tract.

The P-type copper-transporting ATPases, ATP7A and ATP7B are crucial for the regulation of copper homeostasis.
- ATP7A mainly resides at the basal membrane of enterocytes and facilitates copper transport into the portal circulation.
- ATP7B is located at the Golgi complex in hepatocytes and moves to the endo-lysosomal cellular compartments upon copper overload. ATP7B has a dual function. In terms of its biosynthetic role, ATP7B facilitates incorporation of copper into apo-ceruloplasmin within the trans-Golgi network to form ceruloplasmin. Furthermore, ATP7B facilitates excretion of copper into the bile via the apical membrane of hepatocytes.

374
Q

Cu associated hepatitis in Labs - causative gene mutation?

A

Mutations in ATP7A & ATP7B genes leading to amino acid substitutions.

375
Q

WSAVA classification of feline inflammatory liver diseases?

A

3 histopath groups:
1) Neutrophilic (acute & chronic)
2) Lymphocytic
3) Chronic cholangitis 2’ to liver flukes (Platynosomum spp. and Amphimerus pseudofelineus)

376
Q

Liver fluke cholangitis in cats - pathogenesis?

A

Endemic - ‘lizard poisoning’ - eating
infected lizards found in the tropics and subtropics. Fluke resides in the GB & biliary ducts of infected cats, creating inflammation within bile ducts & portal areas.
High burden –> chronic mucoid D+ & icterus. Non-specific signs when chronic (adult flukes persist).

377
Q

Hepatocutaneous syndrome - signalment, skin lesion appearance & locations?

A

Signalment: small-med sized dogs, males > females, median onset 10yo. Breeds reported - Shetland, Cockers, WHWT.

Skin: crusting, ulcerative, painful dermatosis
that affects the mucocutaneous junctions, pressure
points, and footpads with classic histologic features of superficial necrolytic dermatitis

378
Q

What do the CCECAI and CIBDAI systems stand for (differences) and what is their clinical utility?

A

Both systems used for scoring dogs with IBD. CIBDAI has also been utilised to assess dogs with acute pancreatitis.

CIBDAI = canine IBD activity index.
= 6 components, attitude/activity, appetite, vomiting, stool consistency, stool frequency, weight loss (see table)

CCECAI = canine chronic enteropathy clinical activity index.
= CIBDAI components + serum [albumin], peripheral oedema & ascites, severity of pruritus.
allows better assessment of therapeutic success

379
Q

Describe the technique of contrast-enhanced ultrasound & its indications.

A

Salavati JVIM 2020
CEUS uses gas-filled microbubbles (usually sulfur hexafluoride) as a tracer to assess tissue perfusion. The microbubbles remain entirely within the intravascular space & have rheology (flow & deformation) similar to RBCS. Excess sulfur hexafluoride is exhaled, and the phospholipid microbubble shell enters the endogenous phospholipid metabolic pathway. The microbubbles have an elimination half-life of ~6mins; >80% of the administered gas is exhaled via the lungs after 11 mins.

Indications:
Humans - assess mucosal healing with IBD
Dogs - evaluate perfusion abnormalities in several organs (focal splenic lesions, adrenal tumors, prostatic disease); assessment of GIT in healthy dogs & cats, assess duodenal perfusion in dogs with CIE & intestinal LSA.

380
Q

a) DGGR lipase vs traditional lipase assay components?

b) Agreement of DGGR lipase with current gold standard tests for diagnosis of pancreatitis?

A

a) DGGR lipase assay = 1,2-O-dilauryl-rac-glycero glutaric acid-(60-methylresorufin) ester (DGGR) substrate. Traditional lipase = 1,2-diglyceride (1,2 DiG) substrate.

b) High level of agreement between DGGR & spec CPL, similar sensitivity. DGGR is cheaper with more rapid turnaround time, used as screening biomarker in routine biochemistry panels.

381
Q

Normal hepatic [copper] in dogs?

A

150-400 μg/g dry weight (parts per million/ppm).

382
Q

Cut-off hepatic Cu level for differentiating primary vs secondary copper hepatopathy?

A

<800ppm likely secondary
>800ppm likely primary

383
Q

What is the current best indicator of cobalamin (Cbl) status in cats & dogs?
What is the role of this indicator in B12 metabolism?

A

Measurement of methylmalonic acid (MMA) concentrations - indicator of Cbl cellular stores.

Adenosyl-Cbl = cofactor for a) conversion of methylmalonyl-CoA to succinyl-CoA via methylmalonyl-CoA mutase, and b) re-methylation of homocysteine via methionine synthase.

B12 deficiency –> decreased methylmalonyl-CoA mutase activity –> increased serum [MMA].
NB: cats don’t have increased [homocysteine].

384
Q

Roles of bile acids?

A
  • Aid in digestion & absorption of lipids in the GIT
  • Signalling molecules
  • Primary BA converted to secondary BA by bacteria with 7α-dehydroxylation capabilities.
  • Secondary BAs inhibit growth & germination of C. difficile (in people, possibly in dogs).
385
Q

1) Which bacteria is involved in bile acid metabolism?
2) Significance in dogs/cats with CE?
3) Diagnostic test available?

A

1) Clostridium hiranonis
Main BA converting bacteria spp in dogs - convert primary BAs to secondary BAs by 7a-dehydroxylation
2) Depleted in CE (also by abx use) –> decreased proportion of secondary BA in colon in these dogs. Can be partially restored with FMT.
3) Included as 1 of 7 bacteria spp. quantified with the faecal dysbiosis index (DI).

386
Q

List primary & secondary bile acids, and their roles.

A

Primary BA:
- Cholic acid, chenodeoxycholic acid
- In the duodenum: solubilise dietary lipids to aid digestion post-prandium

Secondary BA:
- Deoxycholic acid, lithocholic acid
- Bind to transmembrane G protein-coupled bile acid receptor GPBAR-1 (AKA TGR5 as signaling molecules)
- Anti-inflammatory properties.
- Lower glucose concentrations by binding to the farnesoid X receptor.

387
Q

Differences in bile acid conjugation between cats & dogs?

A
  • Cats: BA exclusively conjugated with taurine (essential AA) - so prone to rapidly developing taurine deficiency with hepatic disease
  • Dogs: taurine or glycine
388
Q

Risk factors for PPDH in dogs & cats?

A

Dogs - Weimaraners
Cats - DMH, DLH (Himalayans, Persians)

389
Q

Ductal plate malformations:
1. Define
2. Phenotypes
3. Complications/consequences

A
  1. DPMs = embryonic abnormalities secondary to dysfunction of the primary cilia that result in defective tubulogenesis & affect the formation of bile ducts. (Primary cilia are present in the liver on only
    cholangiocytes, not hepatocytes).
  2. Caroli DPM (malformative medium-to-large bile ducts with irregularly distended or variably sacculated silhouettes, evaginating diverticular buds, and occasional scattered circumferential satellite bile duct profiles, similar to the embryologic ductal plate) or proliferative-like DPM. 1st r/o mechanical cholestasis before diagnosis.
    Expansive cystadenoma DPM - cats > dogs
  3. Pre-sinusoidal hypertension develops due to non-compliant portal fibrosis. Congenital hepatic fibrosis –> variable clinical progression but can lead to acquired PSS & ascites.
390
Q

Which immunohistochemical stains are used to diagnosed copper storage hepatopathy?

A

Rhodanine stain - highlights copper granules as bright orange-red cytosolic inclusions. Limitation - stain fades over time esp with light exposure (overcome by digitally staining fresh slides).

391
Q

Copper storage hepatopathy
- Breeds
- Causal gene mutation?
- Pathogenesis

A
  • Bedlington Terriers, Dobers, Labs
  • COMMD1 - homozygous deletion of exon 2 (Bedlington)
  • SNP (all 3 above)

Complete absence/dysfunction of ATP7β (Cu transporter protein responsible for Cu transport into plasma protein ceruloplasmin & Cu bile elimination)

392
Q

Describe how copper accumulation causes liver injury.

A

Cu exists in an oxidized (cupric [Cu2+]) or reduced (cuprous [Cu1+]) state - so functions as electron acceptor or donor. Allows Cu to participate in redox cycling reactions that promote generation of ROS.
Haber-Weiss/Fenton reaction: generates superoxide (O2−), hydroxyl (OH) radicals & other ROS from H2O2. Effects of ROS: break DNA strands, ER stress & oxidative injury to cell & mitochondrial membranes, impair protein synthesis + promote cell death pathways. Oxidative injury –> consumptive depletion of hepatocytes & mitochondiral antioxidants (glutathione & a-tocopherol) –> perpetuates oxidative injury.
Decreased hepatic & plasma gluthathione & vit E [ ]
Can also exacerbate oxidative injury caused by concurrent extra-hepatic illness (due to glutathione depletion)

393
Q

Describe histopath findings encountered with copper storage hepatopathy.

A
  1. Accumulation of refractile eosinophilic cytosolic granules in centrilobular (rather than periportal) hepatocytes. Often colocalize with lipofuscin (tan-colored product derived from oxidized membrane lipids).
  2. Copper pigment granulomas - cellular response to dead/dying hepatocytes; populated by macrophages (containing phagocytized hemosiderin, copper, and lipofuscin-laden debris) > fewer lymphocytes, occ Np. Can extend to all zones with progressive disease
  3. Lymphohistiocytic infiltrates
  4. Hepatocyte microvesicular lipid vacuolation - result of mitochondrial & ER injury, seen in severe disease
  5. Mp may sequester iron (phagocytosis of heme-rich cell debris)
  6. Progressive disease - parenchymal remodelling & fibrosis, see regenerative nodules.
  7. Advanced disease - loss of acinar structures & parenchymal distinction. Grossly small pale firm liver with many nodules.
  8. With cirrhosis, Cu accumulates in areas of inflammatory infiltrates or at the margins of regenerative nodules
394
Q

What are indications for initiating copper chelation therapy in dogs?

A

> 1500 mcg/g dry weight regardless of distribution
750 mcg/g dry weight if there is centrilobular accumulation esp in predisposed breeds

Center JAVMA 2021 update: >/=600mcg/g DW if histologic lesions seen with hepatocyte Cu accumulation or if fluctuating ALT activities are seen with no alternative identifiable cause. (as low as 600mcg/g has been associated with copper storage hepatopathy).

395
Q

What are 2 rare complications of severe copper storage hepatopathy in dogs?

A
  1. Acute, severe panlobular hepatic necrosis - associated with massive Cu release from damaged hepatocytes –> may cause markedly increased circulating [Cu] & haemolysis. Grossly liver appears normal/plump or has soft pale-yellow necrotic foci.
  2. Acquired Fanconi syndrome (euglycemic glucosuria > acute proximal tubular injury). Can visualise Cu accumulation in PT epithelium of renal biopsies with Rhodanine staining. Clinical recovery possible with intensive supportive care.
396
Q

What are 2 rare complications of severe copper storage hepatopathy in dogs?

A
  1. Acute, severe panlobular hepatic necrosis - associated with massive Cu release from damaged hepatocytes –> may cause markedly increased circulating [Cu] & haemolysis. Grossly liver appears normal/plump or has soft pale-yellow necrotic foci.
  2. Acquired Fanconi syndrome (euglycemic glucosuria > acute proximal tubular injury). Can visualise Cu accumulation in PT epithelium of renal biopsies with Rhodanine staining. Clinical recovery possible with intensive supportive care.
397
Q

Liver copper accumulation in cats - causes & differences with dogs?

A

Cats with slowly progressive cholangitis –> cholestasis –> periportal Cu accumulation.
Vs dogs - pathological hepatic Cu accumulation is centrilobular, cholestasis is an uncommon cause for significant Cu accumulation (even with EHBDO)

398
Q

What are the key GI bacterial phyla in dogs and cats?

A

Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Actinobacteria

399
Q

What RBC abnormalities are more common in dogs with GI lymphoma vs chronic enteropathy?

A

Parachini-Winter JAVMA 2019
Anaemia
3+ RBC anomalies, (Sn 71%, Sp 70%)
Particularly presence of eccentrocytes (29% LSA vs 4% CIE)

Eccentrocytes reflect oxidative injury.

400
Q

Differences in oesophagus musculature between dogs & cats? Implications for treatments?

A

Dogs - striated muscle throughout oesophagus
Cats - upper 80% striated, distal 20% smooth muscle
Smooth muscle agents (metoclopramide & cisapride) don’t work to increase oesophageal motility in dogs, but may work to increase distal oesophageal motility in cats.

401
Q

What are the 2 types of cricopharyngeal dysphagia?

A
  1. Achalasia = a primary esophageal motility disorder; results from a selective loss of inhibitory myenteric neurons leading to failure of the LES to relax in response to a pharyngeal swallow and impaired esophageal peristalsis.
  2. Assynchrony = lack of coordination between UES relaxation & pharyngeal contraction.

Clinical signs are indistinguishable.

402
Q

Which drugs may be associated with GB mucocoele formation?

A

Thyroxine, trilostane, imidocloprid (esp in Shetland sheepdogs)

403
Q

Nutritional deficiency in …… is of potential concern in dogs with GBM, due to ……

A

Lipid-soluble substances
EHBDO

404
Q

DDx for hyperammonemia in dogs/cats?
1 blood test that may help differentiate?

A

Congenital vs acquired PSS, inborn errors of metabolism (IEM; urea cycle enzyme deficiency)
BAST - normal with IEM
Also IEM - young animals. Can measure urine metabolites. Reported in Irish Wolfhounds (hypercitrullinemia). Pekingese, Yorkie; American shorthair, Maine coon.

405
Q

What are the 3 main zymogens in the exocrine pancreas? What 2 mechanisms prevent early activation of pancreatic enzymes & autodigestion?

A

Zymogens - trypsinogen (main one), chymotrypsinogen, procarboxypeptidase
Mechanisms:
- Presence of chyme required –> enterocytes (brush border enzymes) release enteropeptidase –> activates some trypsinogen to trypsin –> newly formed trypsin assists in activating all three zymogens
- Intracellular pancreatic secretory trypsin inhibitor (PTSI) released to inhibit early activation of pancreatic enzymes

406
Q

What are the key players regulate pancreatic enzyme secretion?

A
  1. Presence of fat and protein in the SI lumen (70% secretions) > thought of food (cephalic phase) (20%) > stomach filling (gastric phase 5-10%)
  2. Secretin (from S cells in duodenum & jejunum) = most impt hormone that stimulates pancreatic secretion containing HCO3- (+ H2O) in response to HCl in chyme entering SI from stomach.
  3. Ach (vagal n.) & cholecystokinin (CCK) –> stimulate release of digestive enzymes (+release of bile into SI).
  4. Local enteric NS.
407
Q

In which breed with chronic pancreatitis may immunosuppressive therapy be beneficial?

A

English Cocker Spaniels
Distinct form of CP vs other breeds, similar to autoimmune CP in humans (histo - duct destruction + anti-CD31 lymphocytic infiltrates around venules and ducts)
Other breeds: usually mixed T-cell infiltration & duct hyperplasia on histo.

408
Q

Which bacteria spp can compete with the host for to utilize the B12-IF-receptor complexes in the development of SI dysbiosis?

A

Bacteroides spp. (other bacteria can only complete for free B12)

409
Q

High folate - causes & mechanisms?

A

SI dysbiosis (Bacteroides spp produce folate)
B12 deficiency (folate share common methionine synthesis pathway. B12 def –> traps & accummulates folate –> can decr after B12 supp)

410
Q

Immunoproliferative LP enteritis has been documented in which breed? What are the characteristic clin path & histological features of this disease?

A

Basenjis.
Marked hypoalb + HYPERglob (don’t have alpha heavy chain dz like in humans). Predisposition to LSA.
Histo of intestinal lesions - increased CD4+ & CD8+ T cells.

411
Q

A specific enteropathy in Irish Setters involves sensitivity to what ingredient? What is another breed with similar sensitivity?

A

Gluten.
SCWTs (PLE).

412
Q

What molecular weight of proteins are associated with immunological responses causing GI disease in dogs & cats?

A

20+kDa
Most common types: beef, dairy, fish (for cats)

413
Q

List 5 dog breeds prediposed to EPI? Differences in most common aetiology?

A

Progressive acinar atrophy
-** GSD, Rough coated collies **(autosomal recessive)
- Chow Chow (congenital hypoplasia also reported)
- English Setters (reported in family)

Chronic pancreatitis
- CKCS

414
Q

TLI:
- Cut-off to diagnose EPI (cats vs dogs)?
- Causes for increased TLI?

A

Dogs: <2.5ug/L (with concurrent CSx) highly diagnostic, <1.9ug/L 100% Sp/Sn.
Cats: <8.0ug/L diagnostic
Increased TLI - pancreatitis, renal disease (decr excretion), pancreatic duct obstruction, post-prandium (12-18hr fast)
Interference - hemolysis

415
Q

What 2 other tests can be considered to diagnose EPI in the event of equivocal TLI results? Cut-offs for EPI vs normal?

A
  1. Faecal pancreatic elastase 1 (FPE1)
    - Zymogen produced exclusively within pancreatic acinar cells. Survives intestinal transit unchanged, also unaffected by intestinal inflammation.
    - <10ug/g faeces diagnostic for EPI, >40ug/g = normal exocrine pancreatic function
  2. TLI stimulation test
    - Measure cTLI before & 20mins after stimulation with secretin/CCK IV
    - Lack of stimulation confirms EPI (subclinical EPI - can have low fasting but normal post stim results)
    - In people gold standard: analyse pancreatic secretions after CCK & secretin stimulation, some studies in dogs (but impractical)
  3. Or…just recheck TLI 1 month after
416
Q

Which pancreatic enzyme formulation is recommended (vs not) for EPI tx?

Complications/possible causes for no clinical response to supp?

A
  • Powdered forms recc (commerical vet products available)
  • Enteric-coated pancreatic enzyme tablets NOT recommended (need pancreatic HCO3- to break down coating, deficient in EPI patients, also don’t recc supp)
  • Raw pancreas not recc (BSE, pseudorabies!)

Causes:
- Too low dose
- Inappropriate formulation (enteric coated tabs)
- HypoB12 (not supp)
- Vit K def > coagulopathy (reported)
- Co-morbidities unaddress (IBD, ARE, pancreatitis)
- Dietary (some dogs may need lower fat)

417
Q

Dietary recommendation for EPI?

A

Highly digestible (low fibre), moderate fat (or adjusted based on patient)
Low fat not proven to improve CSx.

418
Q

Normal CBD diameter in dogs vs cats?

A

Dogs: not normally seen on US, <3mm
Cats </= 4mm
(shouldn’t see intrahepatic bile ducts)

419
Q

Liver of dog - most likely ddx? Common concurrent clinical manifestation?

A

Hepatocutaneous syndrome. Honeycomb appearance (hypoechoci nodules with hyperechoic liver parenchyma)
Superficial necrolytic dermatitis - pedal skin lesions

420
Q

What gene mutation is associated with predisposition to pancreatitis in dogs, and what does it encode? Which breeds?

A

SPINK-1 gene (serine protease inhibitor, Kazal type 1).
Encodes pancreatic secretory trypsin inhibitor (PTSI).
PTSI/SPINK-1 binds to trypsin & keeps it in inactive form (trypsinogen) > so prevents early activation of trypsin & autodigestion.
Mini Schnauzers.

(Also can get genetic mutations of trypsinogen (leading to resistance to hydrolysis)

421
Q

Drugs & toxins associated with canine pancreatitis?
What infectious agent is commonly associated with pancreatitis in dogs?

A

Idiosyncratic - azathioprine, L-aspar, clomipramine, meglumine antimionate, phenobarbitone, KBr, combo phenobarb/KBr
True risk factor - sulphonamides
Toxicity (rare) - Zn, lily
Babesia (rossi&raquo_space; gibsoni)

422
Q

Stimuli for zymogen activation > autoactivation of pancreatic enzymes?

A
  • Post-prandial enterokinase release & entry into portal circulation
  • Bile reflux into pancreatic ducts or due to duodenal obstruction
  • Obstruction of pancreatic acinar cells/ducts
  • Thrombin release during bacterial toxemia, ischemia, hypoxia
  • Oxidative stress
  • ROS (produced in proinflammatory response)
  • Hypotension (decreased pancreatic blood flow)
  • Cathepsin B (protease; trypsinogen activator)
  • Acute hyperCa (rare; possible MOA - Ca deposition in the pancreatic duct > Ca activates trypsinogen)
423
Q

Which cells is implicated in the development of pancreatic fibrosis?

A

Pancreatic stellate cells (peri-acinar) - role in regulating ECM production.
CCK & oxidative stress also sensitise acinar cells to injury & necrosis

424
Q

Cats with pancreatitis - what associated condition may develop that is of major concern?
1 biochemical marker that is a negative prognostic indicator?

A

Often associated with SI and/or liver disease.
Hepatic lipidosis.
Vit B12 & vit K deficiencies, hypoK common.

Ionized hypoCa (not in dogs)

425
Q

Based on the ACVIM consensus statement, what are the benefits & recommendations for anti-inflammatory/ immunosuppressive therapy for cats with severe pancreatitis?

A

Cats that are not hyperglycemic:
- AI doses (0.5-1mg/kg PO q24hr tapering), but some recommend IS doses (2mg/kg q12h x5d then 1mg/kg q12h for 6 wks tapering)
Hyperglycemic cats:
- Cyclosporine 5mg/kg PO q24hr for 6 wks. Risks of unmasking latent toxoplasmosis (long term high dose).
Re-evaluate & recheck spec FPL after 2-3 weeks. If improving continue slow taper.

426
Q

When should surgical treatment of EHBDO be considered?

A
  • Acholic faeces (indicates complete biliary obstruction)
  • Failure of icterus to improve >10d (in humans med tx pursued provided resolves within a month)
  • GB rupture
427
Q

Breeds predisposed to chronic hepatitis & lobular dissecting hepatitis? Which breeds tend to have earlier onset of disease?

A

ACVIM consensus
Bedlington Terrier, Dobers, Labs, Dalmatians, Cockers, Eng Springer Spanels, WHWT, Standard Poodles
Cockers & Standard Poodles also for lobular dissecting hepatitis
Dalmatians, Dobers, Eng Springer Spaniels usually younger

428
Q

What molecular biomarker is more sensitive than ALT for dogs with chronic hepatitis?
Which clin path abnormalities are negative prognostic factors?

A

microRNA-122
HyperBIL, increased APTT/PT, hypoalb, not ALT incr.
Ascites (except Cockers), more severe fibrosis
Overall MST 561d, 22d with ascites (likely cirrhosis)

429
Q

What is the potential impact of sampling regenerative nodules & fibrotic regions on interpreting hepatic copper concentrations?

A

Both may underestimate Cu

430
Q

Deficiency in ….. may be associated with chronic hepatitis in affected Cocker Spaniels?

A

alpha-1 anti-trypsin (protease inhibitor) deficiency (accumulation of abnormal A1AT in hepatocytes)

431
Q

List 3 treatment options for copper chelation in dogs with copper storage hepatopathy? MOA & AE?

A

1. D-penicillamine
- Binds Cu in blood to form water-soluble complexes > increased urinary excretion
- Increases metallothionein in hepatocytes (detoxifies intracellular Cu&raquo_space; excreted in urine) & enterocytes (increases faecal elimination).
- Anti-inflam (reduce T cell activity) + anti-fibrotic effects (reduce collagen X-linking)
- AE: GI signs common, proteinuria (glomerulonephritis), skin eruptions (rare)

  1. Zinc
    - Interferes with Cu absorption in the GIT via inducing metallothionein
    - Don’t give with D-pen (latter binds Zn)
    - AE: GI signs common
  2. Dietary copper restriction (prescription diets with <0.12mg/100kcal)

+/- SAME/vit E (for Cu-associated oxidative injury)

432
Q

What renal changes may occur with hepatic copper toxicosis? Do these improve with treatment?

A

Proximal tubular dysfunction > Fanconi-like syndrome. Euglycemic glucosuria, aminoaciduria, granular casts in some dogs.
Yes resolved after copper chelation therapy.

433
Q

How can the measurement of protein C activity be useful in the diagnosis of hepatobiliary disease in dogs?

A

Differentiation of congenital PSS from PHPV/MVD
Protein C activity >70% in MVD (marked MVD can have borderline levels)
<70% in cPSS, increased to >70% after successful shunt attenuation

434
Q

What coagulation abnormalities on TEG are common in dogs with:
1) Congenial PSS
2) Chronic hepatitis
3) Acute liver failure
4) Biliary disease (GBM)?

A

CPSS - hypercoagulable (decreased protein C & AT; incr vWF & FVIII). High fibrinogen with high G on TEG > more likely to develop HE (pro-inflammatory state > thrombosis)

CH - hyperfibrinolytic & hypocoagulable with cirrhosis (decr platelets, incr PT/PTT, decr fibrinogen)

Acute liver failure - hyperfibrinolytic (decr protein C & AT, incr APTT, decr platelets)

Biliary dz/GBM: hypercoagulable

435
Q

Contraindications for liver biopsies?

A
  • PT/APTT > 1.5x URI
  • Platelets <50-80K
  • BMBT >4mins (dogs), >3.3mins (cats)
  • Anemic PCV <30%
  • Fibrinogen <100mg/dL (<50% lower RI)
  • vWF activity <50%
  • Ascites (relative contraindication; purported incr bleeding risk & more challenging to do lap bx)
  • Infectious dz (may spread by bx)
  • Presumed HSA (go for excisional bx)
  • Other co-morbidites making patient unstable for GA
436
Q

What is the main stimulus for hepatic fibrosis formation?

A

Transforming growth factor-b = most potent fibrogenic inflammatory cytokine, pdtn by Kupffer cells. (other cytokines e.g. PDGF)
Activation of hepatic stellate cells > express smooth muscle-specific a-actin & secrete high-density matrix and collagen into the space of Disse.

437
Q

Scottish Terriers with vacuolar hepatopathy are at increased risk of acquiring what disease? What is the pathogenesis behind vacuolar hepatopathy?

A

Hepatocellular carcinoma.
50% dogs have signs of HAC, but variable adrenal function test results (increased progesterone & androstenedione post ACTH stim).

438
Q

What are reported causes of destructive cholangitis in dogs? What similar clinical sign does it share with bile duct obstruction?

A

Idiosyncratic reaction to TMPS, canine distemper, some hepatotoxins.
Causes v severe intra-hepatic cholestasis & icterus –> acholic faeces.
Histo - biliary epithelium necrosis

439
Q

What is the WSAVA definition of chronic hepatitis?

A

Key histologic features: lymphocytic, plasmacytic, or granulomatous inflammation (portal, multi focal, zonal, panlobular) or some combination, along with hepatocyte cell death and variable severity fibrosis and regeneration

440
Q

What is lobular dissecting hepatitis?

A

Lobular inflammation and disruption of hepatic cords by fine fibrous septa, hepatocyte necrosis, and marked ductular reaction

441
Q

What is the most common cause of chronic hepatitis?

A

Idiopathic

442
Q

What are potential infectious etiologies that may result in chronic hepatitis?

A

No strong evidence for underlying viral etiology

Other infectious causes with sporadic associations with chronic hepatitis:
Leptospirosis MAY induce a chronic pyogranulomatous response after acute infection
Bacillus pilliformis, Helicobacter canis, Bartonella spp. — have been identified in dogs with CH, but minimal evidence to suggest that they CAUSE CH
Ehrlichia canis
Babes is - causes non-suppurative hepatitis
Anaplasma - subacute hepatitis
Leishmania - causes granulomatous inflammation, chronic hepatitis

Other: Neospora, toxoplasma, Sarcocystis, hsitoplasma, mycobacteria, schistosomiasis, visceral larval migrants

443
Q

What are potential drugs/ toxins that may results in chronic hepatitis?

A

Drugs/ toxins more commonly cause acute liver injury but cirrhosis and CH can be potential sequelae

E.g. phenobarbital, primidone, phenytoin, lomustine — all of these can cause chronic hepatitis

Other drugs: carprofen, oxibendazole, amiodarone, aflatoxin, cycasin - more commonly cause acute hepatopathy

Herbal and dietary supplements

MOST COMMON - hepatic copper excess - copper associated chronic hepatitis

444
Q

What is the genetic mutation that causes copper hepatitis in Bedlington Terriers?

A

Autosomal recessive deletion in exon 2 of ATP7B associated protein (COMMD1)

445
Q

What genetic mutations may result in copper hepatopathy in Labrador retrievers?

A

ATP7B gene - predisposes to copper accumulation

ATP7A gene - intestinal copper transporter, which protects against copper accumulation

446
Q

What is the copper concentration that triggers copper hepatitis?

A

This is unknown

447
Q

What is an acute presentation of copper hepatitis?

A

Acute Neuro inflammatory crisis - causes Coombs negative hemolytic anemia

448
Q

Copper accumulation in the kidneys associated with underlying copper storage disease can cause what?

A

Acquired Franconia like syndrome

449
Q

What are the three main diagnostic criteria for confirmation of copper hepatitis/hepatopathy?

A

Histological evidence of chronic hepatitis associated with hepatic copper accumulation - copper typically centrilobular, or in zone 3

histochemical copper straining showing hepatocyte copper accumulation in centrilobular area

Hepatic copper with copper concentrations usually >1000 mcg/g dw liver

450
Q

What is considered the “grey zone” of quantitative hepatic copper concentrations?

A

Between 600 and 1000 mcg/g dw liver

451
Q

What is alpha 1 anti trypsin deficiency (AAT) ? Which breeds are predisposed?

A

It is a metabolic condition caused by abnormal hepatic processing of alpha 1 anti trypsin. This causes hepatocyte retention of abnormally folded proteins, causing chronic hepatitis.

Breeds - American and English Cocker Spaniels

452
Q

What is erythropoietin protoporphyria? Which breed has this disease been reported in?

A

Disorder of porphyrin metabolism, results in accumulation of porphyrins in hepatocytes

It has been reported in GSD

453
Q

What age range and what breed does lobular dissecting hepatitis typically present?

A

Younger age

Male

Cocker spaniel predisposition

454
Q

Ultrasonographically, is the liver typically HYPO or HYPERechoic to the spleen?

A

Order of hyper to hypoechoic = Spleen —> liver —> kidney

Liver should be hypoechoic to the spleen

455
Q

How many portal triads are needed for appropriate evaluation of hepatic architecture?

A

12-15 portal triads

456
Q

How many minimum laparoscopic or surgical specimens should be obtained during liver biopsy and how should these specimens be allocated?

A

Minimum 5

1 piece for copper
1 piece for aerobic and anaerobic culture
3 pieces for histopath

457
Q

What is the main histopathologic hallmark of disease chronicity? What changes indicate end stage disease?

A

Fibrosis

Final fibrosis stage/ indicator of end stage disease - prominent bridge septa and nodular regeneration of hepatocytes

458
Q

What are special stains to evaluate for copper?

A

Rhodanine or rubes if acid

459
Q

What does periportal copper accumulation indicate?

A

Nonspecific - may indicate cholestasis/ be secondary to primary process

460
Q

What is the gold standard for tissue copper quantification? What other tests of copper can be done if gold standard is not available?

A

Atomic absorption spectroscopy - gold standard

Other - digital quantification of copper using scanning of rhodanine stained tissue

461
Q

If pyogranulomatous inflammation is noted on histopathologic, what additional testing should be performed?

A

Infectious disease testing

462
Q

In dogs with copper hepatopathy, how long should copper be restricted? How much dietary copper is recommended? Can this be done in place of chelation?

A

Life long

< 0.12 mg/100 kcal of copper

No it can’t be done in place of chelation

463
Q

What is the mechanism of action of D-penicillamine?

A

Copper chelation of choice in copper hepatopathy

Binds hepatic copper to be eliminated in urine and increases metallothionein in hepatocytes (detoxifies intracellular copper) and enterocytes (facilitates fecal elimination). It also has mild anti- inflammatory and anti-fibrotic properties

464
Q

How long should treatment with D-penicillamine be continued in the case of copper hepatopathy?

A

Treat for one month beyond ALT resolution, then stop

465
Q

Should D. Penicillamine and zinc be given together?

A

NO you idiot, their effects negate each other

466
Q

What are alternative second line copper chelating agents?

A

Choline tetrathiomolybdate

Trientene

467
Q

What are poor prognostic indicators in a dog with chronic hepatitis?

A 
Hyperbilirubinemia
PT/PTT prolongation
Hypoalbuminemia
Ascites 
Extent of fibrosis on biopsy
468
Q

In a dog (or cat) with underlying hepatic dysfunction, what is a potential consequence of administering a blood transfusion?

A

Hepatic encephalopathy - stored blood contains products of anaerobic metabolism/ protein breakdown, may provoke HE event

ACVIM SAIM (2023) (19 decks)

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