GI | Liver | Pancreas

Question 1

What are the layers of the GI wall?

Answer 1

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

Question 2

What are slow waves in the GIT?

Answer 2

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

Question 3

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

Answer 3

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

Question 4

Do the slow waves in the GIT cause muscle contraction?

Answer 4

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

Question 5

What are spike potentials in GIT?

Answer 5

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

Question 6

In the nerve fibers how are AP generated?

Answer 6

By rapid entry of Na into nerve through Na channels

Question 7

How are the action potentials different in the GIT?

Answer 7

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

Question 8

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

Answer 8

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

Question 9

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

Answer 9

More negative = Hyperpolarized (less excitable)

Question 10

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

Answer 10

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

Question 11

What are tonic contractions in the GIT?

Answer 11

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

Question 12

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

Answer 12

Enteric Nervous System

Question 13

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

Answer 13

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

Question 14

Which plexus in GIT controls GI movements?

Answer 14

Myenteric Plexus (Auerbach’s)

Question 15

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

Answer 15

Submucosal Plexus (Meissner’s)

Question 16

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

Answer 16

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

Question 17

What is the neurotransmitters that results in excitation in GIT?

Answer 17

Acetylcholine

Question 18

What is the neurotransmitters that results in inhibition in GIT?

Answer 18

Norepinephrine

Question 19

How does parasympathetic stimulation affect the ENS?

Answer 19

Increases activity of ENS

Mainly vagus nn (some through pelvic nn)

Question 20

How does sympathetic stimulation affect the ENS?

Answer 20

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

Question 21

What is the gastrocolic reflex?

Answer 21

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

Question 22

What is the enterogastric reflex?

Answer 22

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

Question 23

What is the colonoileal reflex?

Answer 23

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

Question 24

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

Answer 24

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

Question 25

Where is gastrin produced?

Answer 25

G cells from antrum, duodenum, jejunum

Question 26

What are the 2 actions of gastrin?

Answer 26

Stimulates: 1. Gastric acid secretion 2. Growth of gastric mucosa

Question 27

Name 3 stimuli that result in secretion of gastrin?

Answer 27

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

Question 28

Where is cholecystokinin secreted?

Answer 28

I cells of duodenum, jejunum, and ileum

Question 29

Name 3 stimuli that result in secretion of cholecystokinin?

Answer 29

1. Protein 2. Fat 3. Acid

Question 30

Name 6 roles of cholecytsokinin.

Answer 30

``` 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) ```

Question 31

Where is secretin secreted from?

Answer 31

S cells from duodenum, jejunum, ileum

Question 32

What are 2 stimuli for secretion of secretin?

Answer 32

1. Acid | 2. Fat

Question 33

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

Answer 33

``` 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 ```

Question 34

What cells secrete gastric inhibitory peptide (GIP)?

Answer 34

K cells of duodenum and jejunum

Question 35

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

Answer 35

1. Protein 2. Fat 3. Carbohydrates (less)

Question 36

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

Answer 36

``` Stimulates: 1. Insulin release Inhibits: 1. Gastric motility (mild) 2. Gastric Acid Secretion ```

Question 37

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

Answer 37

Glucose-dependent insulinotrophic peptide

Question 38

Which cells secrete motilin?

Answer 38

M cells of stomach, duodenum, jejunum

Question 39

Name 3 things that stimulate the secretion of motilin.

Answer 39

1. Fat 2. Acid 3. Nerve

Question 40

What does motilin do in GIT?

Answer 40

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

Question 41

What are the 2 types of movement in the GIT?

Answer 41

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

Question 42

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

Answer 42

Stimulus = Distenstion (stretching) caused by material | Some chemical and physical irritation, strong parasympathetic nervous signals

Question 43

What is the function of the myenteric plexus in peristalsis?

Answer 43

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

Question 44

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

Answer 44

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

Question 45

What is the "law" of the gut?

Answer 45

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

Question 46

Name 2 mixing movements in the GIT?

Answer 46

1. Peristalsis again sphincter = churning of content | 2. Local intermittent constrictive contractions within gut wall (chopping and shearing contents)

Question 47

What is splanchnic circulation?

Answer 47

• 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

Question 48

Which nutrient is NOT carried in portal blood and why?

Answer 48

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

Question 49

What are the 3 phases of swallowing?

Answer 49

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

Question 50

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

Answer 50

1. Primary peristalsis - continuous wave from pharynx | 2. Secondary Peristalsis = from distension of esophagus (controlled by myenteric NS)

Question 51

What are the 3 main motor functions of the stomach?

Answer 51

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

Question 52

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

Answer 52

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

Question 53

Describe the basic electrical rhythm of the stomach.

Answer 53

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

Question 54

What are hunger contractions?

Answer 54

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

Question 55

What controls stomach emptying?

Answer 55

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

Question 56

In general what regulates stomach emptying?

Answer 56

Signals from stomach and duodenum (potent)

Question 57

What are the 2 gastric factors that control stomach emptying?

Answer 57

Promote emptying = increased pyloric pump 1. Gastric food volume (stretch) 2. Gastrin release

Question 58

What are the 2 duodenal factor that control stomach emptying?

Answer 58

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)

Question 59

What are the 2 major movements in the SI?

Answer 59

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)

Question 60

Which hormones increased motility in SI?

Answer 60

gastrin, CCK, insulin, motilin, serotonin

Question 61

Which hormones decreased motility in SI?

Answer 61

Secretin and glucagon

Question 62

What is the gastroielal reflex?

Answer 62

After a meal = increased peristalsis in ileum = emptying

Question 63

What are the 2 major movements of the colon?

Answer 63

1. Mixing movements - large circular contractions | 2. Propulsion movements = MASS MOVEMENTS (dt gastrocolic and duodenocolic reflexes = distension)

Question 64

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

Answer 64

1. Intrinsic Reflex (local ENS - myenteric plexus) | 2. Parasympathetic Defecation Relfex (via pelvic nn) = VERY POWERFUL peristalsis and inhibits internal anal sphincter?

Question 65

Which anal sphincter is under voluntary control?

Answer 65

External anal sphincter

Question 66

Which nerves control the parasympathetic defecation reflex?

Answer 66

Pelvic nn

Question 67

What is the peritoneointstinal reflex?

Answer 67

irritation of peritonenum = intestinal paralysis

Question 68

What is renointestinal reflex and vesicointestinal reflex?

Answer 68

Inhibits intestinal activity due to kidney or bladder irritation

Question 69

What are the two layers of muscles in the GIT?

Answer 69

1. Circular muscles | 2. Longitudinal muscles

Question 70

What is the name of gastrin secreting tumors?

Answer 70

Zollinger-Ellison Syndrome within the pancreas

Question 71

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

Answer 71

Slow waves = Not AP but oscillating depolarization and repolarization

Question 72

What is the action potential in GIT dependent on?

Answer 72

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

Question 73

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

Answer 73

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

Question 74

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

Answer 74

Ca 2+ open resulting in Ca2+ entering cell = Depolarization | K+ open resulting in K+ OUT of cell = Repolarization

Question 75

What do neural and hormonal input influence in GIT?

Answer 75

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

Question 76

During fasting what type of gastric contraction periodically occurs?

Answer 76

Migrating myoelectric complexes = mediated by motiliin

Question 77

What is another name for pits?

Answer 77

Crypts of Lieberkuhn = Secretory cells in GIT

Question 78

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

Answer 78

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

Question 79

What is mucus made of?

Answer 79

Water, electrolytes, glycoproteins

Question 80

What are the 6 magic properties of mucus?

Answer 80

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)

Question 81

What are the 2 types of secretions from salivary glands?

Answer 81

1. Serous = Ptyalin (a-amylase) = Digest starch | 2. Mucus = Mucin = Lubrication

Question 82

What is ptyalin?

Answer 82

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

Question 83

What is the primary secretion from salivary glands?

Answer 83

Either ptyalin or muscus with same electrolyte composition as ECF

Question 84

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

Answer 84

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)

Question 85

What components are in salivary to attack bacteria?

Answer 85

1. Thiocyanate ions 2. Lysozyme 3. Ig

Question 86

What is the primary nerous control of saliva?

Answer 86

Parasympathetic = 2 salivary nuclei in brainstem | Stimulated by high centers (appetite) or something on tongue

Question 87

Discuss the blood flow in the salivary glands.

Answer 87

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

Question 88

What is the primary secretion in the esophagus?

Answer 88

MUCUS for Lubrication (simple and compound mucous glands)

Question 89

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

Answer 89

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

Question 90

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

Answer 90

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

Question 91

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

Answer 91

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

Question 92

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

Answer 92

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

Question 93

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

Answer 93

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

Question 94

Which cell type secretes HCl?

Answer 94

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

Question 95

Which cell type secretes intrinsic factor (dog)?

Answer 95

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

Question 96

Which cell type secretes pepsinogen?

Answer 96

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

Question 97

How is pepsinogen activated?

Answer 97

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

Question 98

What stimulates the conversion of pepsinogen into pepsin?

Answer 98

HCl

Question 99

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

Answer 99

1. Acetylcholine (vagus n. and gastric enetric plexus) | 2. Acid in the stomach

Question 100

What does ECL cells stand for?

Answer 100

Enterochromaffin-Like cell (ECL cell)

Question 101

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

Answer 101

ECL cells

Question 102

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

Answer 102

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

Question 103

Which cells make gastrin?

Answer 103

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

Question 104

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

Answer 104

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

Question 105

Which secretagogue is the most important in gastric acid secretion?

Answer 105

Histamine!

Question 106

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

Answer 106

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

Question 107

What controls the cephalic phase of gastric secretion?

Answer 107

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

Question 108

What controls the gastric phase of gastric secretion?

Answer 108

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

Question 109

What controls the intestinal phase of gastric secretion?

Answer 109

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

Question 110

How is gastric secretion inhibited?

Answer 110

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)

Question 111

What happens in the stomach glands between meals?

Answer 111

They make mucus, almost NO acid!

Question 112

What is the pancreatic duct and which species have it?

Answer 112

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

Question 113

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

Answer 113

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

Question 114

What are the two main functions of pancreatic secretions?

Answer 114

1. Digestive enzymes | 2. Na bicarbonate

Question 115

How are pancreatic enzymes secreted?

Answer 115

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

Question 116

Which pancreatic enzyme can activate all the other pancreatic enzymes?

Answer 116

Trypsin

Question 117

What 3 pancreatic enzymes are responsible for protein digestion?

Answer 117

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

Question 118

What pancreatic enzyme is responsible for carbohydrate digestion?

Answer 118

Pancreatic amylase (starch into disaccharides and trisaccharides)

Question 119

What 3 pancreatic enzymes are responsible for fat digestion?

Answer 119

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

Question 120

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

Answer 120

Trypsin Inhibitor | Prevents activation of zymogens in pancreas or ducts or intracellular

Question 121

Which cells in the pancreas make bicarbonate?

Answer 121

Epithelial cells that line the ductules and ducts | Role of bicarbonate is to neutralize acid from stomach chyme

Question 122

What are the steps in making bicarbonate in the pancreas?

Answer 122

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

Question 123

What are the 3 main stimuli for pancreatic secretion?

Answer 123

1. Acetylcholine 2. Cholecystokinin (CCK) 3. Secretin

Question 124

Which hormones control release of pancreatic fluid and bicarbonate?

Answer 124

Secretin

Question 125

Which hormones control release of pancreatic digestive enzymes?

Answer 125

``` Vagal stimulation (acetylcholine) Cholecystokinin (CCK) ```

Question 126

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

Answer 126

Vagus n. and ENS stimulation

Question 127

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

Answer 127

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

Question 128

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

Answer 128

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

Question 129

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

Answer 129

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

Question 130

What are the 3 phases of pancreatic secretion?

Answer 130

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)

Question 131

What controls the cephalic phase of pancreatic secretion?

Answer 131

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

Question 132

What controls the gastric phase of pancreatic secretion?

Answer 132

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

Question 133

What controls the intestinal phase of pancreatic secretion?

Answer 133

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

Question 134

What are the two main roles of bile?

Answer 134

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)

Question 135

What are the two stages of bile secretion?

Answer 135

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)

Question 136

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

Answer 136

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

Question 137

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

Answer 137

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

Question 138

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

Answer 138

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

Question 139

How are bile salts made?

Answer 139

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

Question 140

What are the two main roles of bile salts?

Answer 140

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)

Question 141

What 4 components are absorbed via micelles with bile salts?

Answer 141

1. Fatty Acids 2. Monglycerides 3. Cholesterol 4. Other Lipids

Question 142

Explain enterohepatic circulation of bile salts?

Answer 142

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)

Question 143

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

Answer 143

1. Brunner's glands = Mucus and bicarbonate | 2. Crypts of Lieberkuhn = Digestive Juices (mucus and watery vehicle)

Question 144

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

Answer 144

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

Question 145

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

Answer 145

1. Goblet Cells = Mucus | 2. Enterocytes = Absorb and secrete water and electrolytes (PURE ECF, alkaline fluid)

Question 146

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

Answer 146

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

Question 147

What are the main villus enzymes?

Answer 147

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

Question 148

Does the large intestinal have villi and Crypts of Lieberkuhn?

Answer 148

No villi | Yes - Crypts of Lieberkuhn

Question 149

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

Answer 149

MUCUS (some bicarbonate) - Lubrication and hold feces together

Question 150

Why is saliva hypotonic?

Answer 150

Active net solute absorption and salivary ducts are impermeable to water

Question 151

Why is neural stimulation of the salivary glands unique?

Answer 151

They are controlled by both parasympathetic and sympathetic NS

Question 152

What are the net results of gastric parietal cells?

Answer 152

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

Question 153

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

Answer 153

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

Question 154

What is the MOA of PPI, omeprazole?

Answer 154

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

Question 155

Name the 2 primary bile acids.

Answer 155

Cholic acid and chenodeoxycholic acid

Question 156

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

Answer 156

1. Salivary alpha amylase (Ptyalin) | 2. Pancreatic amylase

Question 157

What enzymes and where are disacchardies hydrolyzed into monosaccharides?

Answer 157

Intestinal Epithelial Enzymes - Within villi in the brush border 1. Maltase 2. Alpha-Dextrinase 3. Lactase 4. Sucrase

Question 158

What does lactase do?

Answer 158

Splits Lactose into galactose and glucose

Question 159

What does sucrose do?

Answer 159

Splits sucrose into fructose and glucose

Question 160

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

Answer 160

Glucose by maltase and alpha-dextinase

Question 161

What are the final products of carbodyhrate digestion?

Answer 161

Monosaccarides that are absorbed immediately into portal blood

Question 162

What 3 locations do carbohydrate digestion occur?

Answer 162

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

Question 163

What is the most important function of pepsin?

Answer 163

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

Question 164

Name 3 places that protein digestion occurs?

Answer 164

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

Question 165

What is the final product of protein digestion?

Answer 165

Amino Acids

Question 166

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

Answer 166

Pepsin

Question 167

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

Answer 167

Pancreatic enzymes: Trypsin. Chymotrypsin, carboxypolypeptidase, proelastase

Question 168

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

Answer 168

Peptidases (aminopolypeptidase, dipeptidase)

Question 169

What is the most important enzyme of fat digestion?

Answer 169

Pancreatic lipase (little by enteric lipase)

Question 170

What is the final product of fat digestion?

Answer 170

Fatty acids and 2-monoglycerides

Question 171

What are essential for emulsification of tryglycerides?

Answer 171

Bile salts and lecithin

Question 172

By what process is water absorbed in the small intestine?

Answer 172

Entirely by diffusion

Question 173

What is the main mechanism of ion absorption in SI?

Answer 173

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

Question 174

What are the 3 final monosaccharides?

Answer 174

1. Glucose 2. Galatose 3. Fructose

Question 175

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

Answer 175

SGLT 1

Question 176

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

Answer 176

GLUT 2

Question 177

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

Answer 177

GLUT 5

Question 178

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

Answer 178

Enterokinase

Question 179

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

Answer 179

Via Na+ co-transporter or less by facilitated diffusion

Question 180

Name the 4 fat soluble vitamins.

Answer 180

Vitamins A, D, E, K

Question 181

What are the 4 steps of Vitamin B12 absorption?

Answer 181

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

Question 182

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

Answer 182

Jejunum

Question 183

What occurs in the colonocytes for Na and K?

Answer 183

Na+ absorption (+++aldosterone) | K+ secretion

Question 184

What are 2 main things that are lost in diarrhea?

Answer 184

HCO3- and K+ = Hypercholermic metabolic acidosis

Question 185

What is the main electrolyte that is secreted by enterocytes?

Answer 185

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

Question 186

What are the 2 main blood supplies for the liver?

Answer 186

Portal vein and hepatic artery

Question 187

What accounts for the huge regenerative capacity of the liver?

Answer 187

HGF (Heptocyte growth factor) produced by mesenchymal cells

Question 188

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

Answer 188

Kupffer cells

Question 189

What are the 3 things in the portal triad?

Answer 189

1. Portal Vein 2. Bile Duct 3. Hepatic Artery

Question 190

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

Answer 190

Within the Space of Disse

Question 191

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

Answer 191

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

Question 192

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

Answer 192

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

Question 193

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

Answer 193

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

Question 194

Name 4 other functions of the liver in metabolism.

Answer 194

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

Question 195

Discuss the excretion of bilirubin.

Answer 195

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

Question 196

What would you expect with bilirubin in hemolysis?

Answer 196

Unconjugated bilirubin high

Question 197

What would you expect with bilirubin in Cholestasis?

Answer 197

Conjugated bilirubin high

Question 198

What would you expect with bilirubin in total EHBDO?

Answer 198

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

Question 199

How is urea formed in the urine?

Answer 199

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!

Question 200

Which cell in the stomach makes intrinsic factor?

Answer 200

Parietal cells

Question 201

What are the 3 major components of acid secretion?

Answer 201

Histamine, Gastrin, ACh

Question 202

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

Answer 202

Somatostatin

Question 203

What are the components of the gastric mucosal barrier?

Answer 203

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

Question 204

What factors slow emptying of stomach?

Answer 204

Carbs, AA, fats | Release of CCK in response to FA and AA

Question 205

What are the 3 major digestive enzymes in the stomach?

Answer 205

``` 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) ```

Question 206

Which breeds get hypertrophic gastropathy?

Answer 206

Basenji, small breed dogs (shih Tzu)

Question 207

Which breed gets atophic gastritis?

Answer 207

Lundehund

Question 208

What can stoamtocytosis tell you on a CBC?

Answer 208

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

Question 209

What are causes of metabolic alkalosis?

Answer 209

· 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)

Question 210

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

Answer 210

Basenjis (with enteropathies)

Question 211

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

Answer 211

``` § Pyloric antrum · Adenocarcinoma (lesser curvature also) § Cardia · Leiomyoma § Diffuse · LSA ```

Question 212

What is the most common site of an adenomatous polyp?

Answer 212

Pyloric antrum

Question 213

Which breeds are predisposed to PLE?

Answer 213

SCWT, Yorkie, Basenji, Lundehund, Shar-Pei

Question 214

What AA def can results in high ammonia in cats?

Answer 214

Arginine def

Question 215

Which coag factor is NOT made by the liver?

Answer 215

Factor VIII

Question 216

What defines DIC?

Answer 216

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

Question 217

What is the most toxic bile acid?

Answer 217

Lithocholic acid

Question 218

How can diuretics exacerbate HE?

Answer 218

Alkalosis and HypoK!!!

Question 219

What tropic factors are important for hepatic growth?

Answer 219

Insulin and Glucagon (from portal blood)

Question 220

What is the toxin in cycad?

Answer 220

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

Question 221

What is the MOA of cycad toxin?

Answer 221

Cycasin: MAM results in GI, hepatotoxin, neurotoxin | MAM alkylates DNA/RNA

Question 222

What are the target organs of cycad toxin?

Answer 222

Cycasin: LIVER, GI, Neuro

Question 223

What is the clinical presentation of cycad toxin?

Answer 223

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

Question 224

What are the main clin path signs of cycad toxin?

Answer 224

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

Question 225

What are the histopath features of cycad toxin?

Answer 225

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

Question 226

What is the definitive test for cycad toxin?

Answer 226

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

Question 227

What antidotes are recommended for cycad toxin?

Answer 227

Charcoal! Shown to be protective!!!!

Question 228

What is the prognosis for cycad toxin?

Answer 228

Cycasin: Guarded - 30-50% mortality

Question 229

What are the known prognostic indicators for cycad toxin?

Answer 229

Higher ALT, T bili, lower albumin (at presentation), prolonged coag = NONSURVIVORS Early charcoal admin was PROTECTIVE!!

Question 230

What is the toxin in amanita?

Answer 230

Alpha-amanitin (1 cap can kill!)

Question 231

What is the MOA of amanita?

Answer 231

Alpha-amanitin: Inhibits RNA polymerase II (no transcription or protein synthesis) Apoptosis of hepatocytes Insulin Release

Question 232

What are the target tissues of amanita?

Answer 232

LIVER Intestines (crypts) Kidneys (prox tubules)

Question 233

What is the onset of CS with amanita?

Answer 233

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

Question 234

What are the clin path changes with amanita?

Answer 234

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

Question 235

What are the histopath findings with amanita?

Answer 235

Pan-lobular hepatocellular necrosis | Acute tubular necrosis

Question 236

How do you make a definitive diagnosis of amanita?

Answer 236

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

Question 237

What is the antidote for amanita?

Answer 237

Silibinin has helped!!! | Charcoal (if early)

Question 238

What is the prognosis for amanita in dogs?

Answer 238

Poor | 50% mortality in dogs

Question 239

What is the toxin in cyanobacteria?

Answer 239

Microcysts aeruginosa (blue green algae) = Microcystins

Question 240

What is the MOA in cyanobacteria toxin?

Answer 240

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

Question 241

What are the target organs of cyanobacteria?

Answer 241

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

Question 242

What is the presentations of cyanobacteria?

Answer 242

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

Question 243

What are the clin path findings with cyanobacteria?

Answer 243

Increased ALP, GGT, bili | Marked increased in ALT (can be less if microcystoin inhibits tansminase synthesis??)

Question 244

What is the histopath finding for cyanobacteria?

Answer 244

Hepatic necrosis - MASSIVE hemorrhage Acute renal tubular necrosis

Question 245

How is a definitive diagnosis of cyanobacteria made?

Answer 245

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)

Question 246

What is the antidote for cyanobacteria?

Answer 246

NONE | Rifampin in mice/rats can inhibit uptake

Question 247

What is the prognosis for cyanobacteria?

Answer 247

GRAVE

Question 248

What is the toxin with aflatoxin?

Answer 248

Aspergillus = Aflatoxin B1 converted to AFB1 8,9 epoxide | esp dogs and poultry

Question 249

What is the MOA of aflatoxin?

Answer 249

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

Question 250

What are the target tissues of aflatoxin?

Answer 250

Liver | Kidney (prox tubules) - CASTS before azotemia

Question 251

What is the CS onset of aflatoxin?

Answer 251

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

Question 252

What are the clin path findings with aflatoxin?

Answer 252

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

Question 253

What are the histopath findings with aflatoxin?

Answer 253

Acute: Centrilobular necrosis ****Diffuse hepatocyte lipid vacuolization**** Chronic: MIXED

Question 254

How do you make a definitive diagnosis of aflatoxin?

Answer 254

ELISA, HPLC, LC/MS for toxin AFB1 in food source (>60 ppb) Serum, liver, urine = Alfatoxin M1

Question 255

What is the antidote for aflatoxin?

Answer 255

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

Question 256

What is the prognosis for aflatoxin?

Answer 256

Guarded, 60% mortality

Question 257

What are the prognostic indicators for aflatoxin?

Answer 257

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

Question 258

What is the MOA of xylitol?

Answer 258

Rapid, severe increased in insulin from Beta cells (6X more than glucose)!! Hepatic depletion of ALP (from metabolism via pentose phosphate pathway)

Question 259

What are the target organs of xylitol?

Answer 259

``` LIVER (>0.5 g/kg) Beta cells (>0.1 g/kg) ```

Question 260

What are the clinical presentation with xylitol?

Answer 260

30 min-1 hrs - Hypoglycemia | 9-72 hrs = Acute hepatic failure

Question 261

What are the clin path findings with xylitol?

Answer 261

Marked increased ALT, bili Hypoglycemia Coagulopathy HypoK, HypoPhos

Question 262

What is the histopath findings with xylitol?

Answer 262

Periacinar-mid zonal necrosis

Question 263

What is the definitive diagnosis of xylitol?

Answer 263

HX, no tests for it

Question 264

What is the antidote for xylitol?

Answer 264

Early emesis, SAMe, dextrose ****Charcoal DOES NOT bind it****

Question 265

What is the prognosis for xylitol?

Answer 265

Good if early, guarded if prolonged hypoglycemia and LEs increased

Question 266

What is a prognostic indicator for xylitol?

Answer 266

Hyperphosphatemia - Poor prognosis

Question 267

What is the MOA of carprofen?

Answer 267

Idiosyncratic cytotoxic hepatocellular reaction (maybe IM) - Labs?

Question 268

What are the target organs for carprofen?

Answer 268

LIVER, kidney, GIT

Question 269

What breed is susceptible to carprofen tox?

Answer 269

Labs

Question 270

What is the onset of carprofen tox?

Answer 270

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

Question 271

What are the clin findings in carprofen tox?

Answer 271

Increased ALT and bili | 2/3 = Proteinuria, glucouria, and granular casts!!!

Question 272

What is the histopath of carprofen tox?

Answer 272

MIXED (necrosis and inflammation)

Question 273

What is the antidote for carprofen tox?

Answer 273

STOP carprofen!!

Question 274

What is the prognosis for carprofen tox?

Answer 274

Good, 100% labs recover | Only 50% in other breeds

Question 275

Does the dose and duration of carprofen predict the prognosis?

Answer 275

NO!!

Question 276

What is the toxin in diazepam?

Answer 276

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

Question 277

What is the target tissue for oral diazepam in cats?

Answer 277

LIVER

Question 278

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

Answer 278

Within first 7 days after oral dosing

Question 279

What are the clin path findings with diazepam in cats?

Answer 279

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

Question 280

What is the histopath with oral diazepam in cats?

Answer 280

Centrilobular necrosis (MASSIVE!)

Question 281

What is the antidote for oral diazepam in cats?

Answer 281

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

Question 282

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

Answer 282

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

Question 283

What are two complications of gastrinomas?

Answer 283

Acid hypersecretion = GI bleeding | Gastric mucosal hyperplasia - Outflow obstructions

Question 284

What are the stimulation test for gastrinomas?

Answer 284

Secretin stimulation and Ca stimulation to increased gastrin

Question 285

What are the tx for gastrinomas?

Answer 285

1. Sx 2. Octerotide 2. Antacids

Question 286

What are risk factors for pancreatitis?

Answer 286

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

Question 287

Can steroids result in pancreatitis?

Answer 287

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

Question 288

What are the 4 safegaurds within pancreas?

Answer 288

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)

Question 289

What is the process of acute pancreatitis?

Answer 289

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

Question 290

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

Answer 290

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

Question 291

What is the most sensitive and specific test for pancreatitis?

Answer 291

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

Question 292

What are potential complications with pancreatitis?

Answer 292

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

Question 293

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

Answer 293

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

Question 294

What protease inhibitor has shown some benefit in pancreatitis?

Answer 294

Aprotinin

Question 295

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

Answer 295

Maropitant

Question 296

Is there a benefit of ABX with pancreatitis?

Answer 296

None seen with cochrane review

Question 297

What are tx for chronic pancreatitis?

Answer 297

``` 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 ```

Question 298

Why should you not used TLI to dx pancreasitis?

Answer 298

Lacks sens for pancreatitis | Can increased with renal failure!

Question 299

What are not useful tests to dx pancreatitis?

Answer 299

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

Question 300

How long can the PLI remain elevated after pancreatitis?

Answer 300

10-12 days

Question 301

Can PLI predict severity on histopath of pancreatitis?

Answer 301

NO!

Question 302

What are the ranges of PLI for pancreatitis?

Answer 302

DOGS >400 | CATS >5.4

Question 303

Is the PLI affected by renal failure?

Answer 303

NO! | But TLI is affected by renal failure

Question 304

What are the two main forms of EPI?

Answer 304

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

Question 305

Which single pancreatic enzyme def has been reported in dogs?

Answer 305

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

Question 306

Are there markers of progression in EPI?

Answer 306

NO! Can be subclinical for years | Early immunosuppression is NOT recommended

Question 307

What is the diagnostics of choice for EPI?

Answer 307

TLI Low

Question 308

Can fecal pancreatitic elastase be used to dx EPI?

Answer 308

Yes, but need to verify with cTLI | Since false + 23% (low elastase and normal cTLI)

Question 309

What % EPI dogs have Vit B 12 def?

Answer 309

About 82%

Question 310

What is a potential complication of EPI?

Answer 310

Mesentric torsion!

Question 311

What is associated with a shorter survival in EPI dogs?

Answer 311

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

Question 312

What % EPI dogs have poor response?

Answer 312

About 20%

Question 313

What are potential reasons for treatment failure in EPI dogs?

Answer 313

1. IBD, DM, SIBO - Need to tx | 2. Need PPI - To prevent pancreatic enzymes from being destroyed

Question 314

What is a complication with pancreatitic extract in EPI dogs?

Answer 314

Oral bleeding (need to reduce dose and wet it)

Question 315

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

Answer 315

Due to high neutrophil elastase

Question 316

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

Answer 316

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

Question 317

Is EPI inherited in GSD?

Answer 317

Based on test mating - NO!

Question 318

What are 6 options for pancreatic dz in cats?

Answer 318

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)

Question 319

What are risk factors for panc in cats?

Answer 319

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

Question 320

What is a common electrolyte abnormality in cats with AP?

Answer 320

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

Question 321

What are 4 complications of AP in cats?

Answer 321

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

Question 322

Why are H2 and H1 blockers recommended in feline panc?

Answer 322

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

Question 323

Which test has been validated in cats for AP?

Answer 323

fPLI

Question 324

What are pulmonary manifestations of GERD?

Answer 324

From chronic microaspiration events 1. Aspiration pneumonia 2. Chronic Bronchitis 3. Interstitial Pulmonary Fibrosis

Question 325

What is the tx for Spirocerca?

Answer 325

Doramectin

Question 326

What are the 3 defensive lines to prevent epithelial damage?

Answer 326

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!!

Question 327

What are the effects of NSAIDs on mucosa?

Answer 327

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

Question 328

What is the stomach worm in cats?

Answer 328

Ollulanus tricuspids Ingesting cat vomit Tx: Fenbendazole

Question 329

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

Answer 329

Physalloptera; Ingestion of cockroach/beetle (IH) or lizards | Tx: Pyrantel

Question 330

What is the recommend tx for Helicobacter?

Answer 330

Amoxicillin, Clarithromycin, and omeprazole for 3 weeks

Question 331

What is the tx for Campylobacter?

Answer 331

Fluoroquinolones

Question 332

Which hookworm can result in pedal pruritus in greyhounds?

Answer 332

Uncinaria stenocephala

Question 333

What is a treatment for round worms?

Answer 333

Fenbendazole

Question 334

What is a tx for hookworms?

Answer 334

Pyrantel

Question 335

What is a tx for tapeworms?

Answer 335

Praziquantel and flea control

Question 336

An increase in which TRL is seen with IBD?

Answer 336

TLR2 | Also 4, 9

Question 337

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

Answer 337

NO!

Question 338

What are the 5 steps of cobalamin absorption?

Answer 338

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

Question 339

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

Answer 339

Border Collies Giant Schnauzer Beagles Aust Shap

Question 340

Name several compounds that are associated with hepatic encephalopathy?

Answer 340

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

Question 341

What are the proposed mechanisms of how ursodeoxycholic acid works?

Answer 341

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)

Question 342

Which breed gets lobular dissecting hepatitis?

Answer 342

Standard Poodles

Question 343

Where is copper location in inherited copper storage dz?

Answer 343

Centrolobular

Question 344

Where is copper located if you have secondary copper accumulation?

Answer 344

Periportal

Question 345

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

Answer 345

COMMD1 or MURR1

Question 346

What is the tx for copper hepatopathy?

Answer 346

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)

Question 347

What is zone 3 necroinflammatory hepatitis?

Answer 347

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

Question 348

What is noncirrhotic portal hypertension?

Answer 348

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

Question 349

What is portal v. hypoplasia?

Answer 349

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

Question 350

Why do PSS get microcytosis?

Answer 350

iron transport defect

Question 351

What % of shunty dogs can have normal bile acids?

Answer 351

21%

Question 352

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

Answer 352

Low with PSS | Normal (>70%) in MVD

Question 353

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

Answer 353

NO!

Question 354

How does portal hypertesion lead to ascites?

Answer 354

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

Question 355

What are precipitating factors of HE?

Answer 355

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)

Question 356

What is a major complication of feline PSS correction?

Answer 356

75% neurologic complications = Central blindness

Question 357

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

Answer 357

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

Question 358

What is the lesion in lymphcytic cholangitis in cats?

Answer 358

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

Question 359

What is the cat live fluck?

Answer 359

Platynosum | Tx: Praziquantel

Question 360

What is lymphocytic portal hepatitis?

Answer 360

Nonspecific thought to be an aging change | Older cats

Question 361

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

Answer 361

ABCB4 transport mutation (phospholipid transporter)

Question 362

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

Answer 362

HAC

Question 363

Does biliary rupture and bile peritonitis have prognostic factor?

Answer 363

NO!!

Question 364

What is the progression with complete occlusion of the CBD?

Answer 364

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

Question 365

What is hepatic lipidosis?

Answer 365

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

Question 366

Do all cats with HE have increased ammonia?

Answer 366

NO!! Ptyalism could be from HE

Question 367

What was associated with worse survival in Hepatic lipidosis?

Answer 367

HypoK Advanced age Decreased PCV

Question 368

What are the mainstays in Tx of hepatic lipidosis?

Answer 368

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

Question 369

Which breed gets idiosyncratic hepatotoxicty to sulfas?

Answer 369

Dobies!!

Question 370

Zones in the liver & implications?

Answer 370

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.

Question 371

Breeds predisposed to copper storage hepatopathy?

Answer 371

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

Question 372

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

Answer 372

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.

Question 373

Copper metabolism pathway and transporter genes involved?

Answer 373

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.

Question 374

Cu associated hepatitis in Labs - causative gene mutation?

Answer 374

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

Question 375

WSAVA classification of feline inflammatory liver diseases?

Answer 375

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

Question 376

Liver fluke cholangitis in cats - pathogenesis?

Answer 376

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).

Question 377

Hepatocutaneous syndrome - signalment, skin lesion appearance & locations?

Answer 377

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

Question 378

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

Answer 378

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*

Question 379

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

Answer 379

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.

Question 380

a) DGGR lipase vs traditional lipase assay components? b) Agreement of DGGR lipase with current gold standard tests for diagnosis of pancreatitis?

Answer 380

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.

Question 381

Normal hepatic [copper] in dogs?

Answer 381

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

Question 382

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

Answer 382

<800ppm likely secondary >800ppm likely primary

Question 383

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

Answer 383

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].

Question 384

Roles of bile acids?

Answer 384

- 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).

Question 385

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

Answer 385

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).

Question 386

List primary & secondary bile acids, and their roles.

Answer 386

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.

Question 387

Differences in bile acid conjugation between cats & dogs?

Answer 387

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

Question 388

Risk factors for PPDH in dogs & cats?

Answer 388

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

Question 389

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

Answer 389

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.

Question 390

Which immunohistochemical stains are used to diagnosed copper storage hepatopathy?

Answer 390

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).

Question 391

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

Answer 391

- 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)

Question 392

Describe how copper accumulation causes liver injury.

Answer 392

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)

Question 393

Describe histopath findings encountered with copper storage hepatopathy.

Answer 393

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

Question 394

What are indications for initiating copper chelation therapy in dogs?

Answer 394

>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).

Question 395

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

Answer 395

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.

Question 396

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

Answer 396

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.

Question 397

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

Answer 397

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)

Question 398

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

Answer 398

Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Actinobacteria

Question 399

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

Answer 399

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.*

Question 400

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

Answer 400

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.

Question 401

What are the 2 types of cricopharyngeal dysphagia?

Answer 401

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.

Question 402

Which drugs may be associated with GB mucocoele formation?

Answer 402

Thyroxine, trilostane, imidocloprid (esp in Shetland sheepdogs)

Question 403

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

Answer 403

Lipid-soluble substances EHBDO

Question 404

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

Answer 404

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.

Question 405

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

Answer 405

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

Question 406

What are the key players regulate pancreatic enzyme secretion?

Answer 406

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.

Question 407

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

Answer 407

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.

Question 408

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

Answer 408

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

Question 409

High folate - causes & mechanisms?

Answer 409

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

Question 410

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

Answer 410

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.

Question 411

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

Answer 411

Gluten. SCWTs (PLE).

Question 412

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

Answer 412

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

Question 413

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

Answer 413

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

Question 414

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

Answer 414

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

Question 415

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

Answer 415

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

Question 416

Which pancreatic enzyme formulation is recommended (vs not) for EPI tx? Complications/possible causes for no clinical response to supp?

Answer 416

- 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)

Question 417

Dietary recommendation for EPI?

Answer 417

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

Question 418

Normal CBD diameter in dogs vs cats?

Answer 418

Dogs: not normally seen on US, <3mm Cats

Question 419

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

Answer 419

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

Question 420

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

Answer 420

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)

Question 421

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

Answer 421

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

Question 422

Stimuli for zymogen activation > autoactivation of pancreatic enzymes?

Answer 422

- 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)

Question 423

Which cells is implicated in the development of pancreatic fibrosis?

Answer 423

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

Question 424

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

Answer 424

Often associated with SI and/or liver disease. Hepatic lipidosis. Vit B12 & vit K deficiencies, hypoK common. Ionized hypoCa (not in dogs)

Question 425

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

Answer 425

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.

Question 426

When should surgical treatment of EHBDO be considered?

Answer 426

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

Question 427

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

Answer 427

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

Question 428

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

Answer 428

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

Question 429

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

Answer 429

Both may underestimate Cu

Question 430

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

Answer 430

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

Question 431

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

Answer 431

**1. D-penicillamine** - Binds Cu in blood to form water-soluble complexes > increased urinary excretion - Increases metallothionein in hepatocytes (detoxifies intracellular Cu >> 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) 2. Zinc - Interferes with Cu absorption in the GIT via inducing metallothionein - Don't give with D-pen (latter binds Zn) - AE: GI signs common 3. Dietary copper restriction (prescription diets with <0.12mg/100kcal) +/- SAME/vit E (for Cu-associated oxidative injury)

Question 432

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

Answer 432

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

Question 433

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

Answer 433

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

Question 434

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

Answer 434

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

Question 435

Contraindications for liver biopsies?

Answer 435

- 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

Question 436

What is the main stimulus for hepatic fibrosis formation?

Answer 436

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.

Question 437

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

Answer 437

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

Question 438

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

Answer 438

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

Question 439

What is the WSAVA definition of chronic hepatitis?

Answer 439

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

Question 440

What is lobular dissecting hepatitis?

Answer 440

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

Question 441

What is the most common cause of chronic hepatitis?

Answer 441

Idiopathic

Question 442

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

Answer 442

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

Question 443

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

Answer 443

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

Question 444

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

Answer 444

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

Question 445

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

Answer 445

ATP7B gene - predisposes to copper accumulation ATP7A gene - intestinal copper transporter, which protects against copper accumulation

Question 446

What is the copper concentration that triggers copper hepatitis?

Answer 446

This is unknown

Question 447

What is an acute presentation of copper hepatitis?

Answer 447

Acute Neuro inflammatory crisis - causes Coombs negative hemolytic anemia

Question 448

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

Answer 448

Acquired Franconia like syndrome

Question 449

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

Answer 449

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

Question 450

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

Answer 450

Between 600 and 1000 mcg/g dw liver

Question 451

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

Answer 451

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

Question 452

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

Answer 452

Disorder of porphyrin metabolism, results in accumulation of porphyrins in hepatocytes It has been reported in GSD

Question 453

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

Answer 453

Younger age Male Cocker spaniel predisposition

Question 454

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

Answer 454

Order of hyper to hypoechoic = Spleen —> liver —> kidney Liver should be hypoechoic to the spleen

Question 455

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

Answer 455

12-15 portal triads

Question 456

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

Answer 456

Minimum 5 1 piece for copper 1 piece for aerobic and anaerobic culture 3 pieces for histopath

Question 457

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

Answer 457

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

Question 458

What are special stains to evaluate for copper?

Answer 458

Rhodanine or rubes if acid

Question 459

What does periportal copper accumulation indicate?

Answer 459

Nonspecific - may indicate cholestasis/ be secondary to primary process

Question 460

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

Answer 460

Atomic absorption spectroscopy - gold standard | Other - digital quantification of copper using scanning of rhodanine stained tissue

Question 461

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

Answer 461

Infectious disease testing

Question 462

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?

Answer 462

Life long < 0.12 mg/100 kcal of copper No it can’t be done in place of chelation

Question 463

What is the mechanism of action of D-penicillamine?

Answer 463

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

Question 464

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

Answer 464

Treat for one month beyond ALT resolution, then stop

Question 465

Should D. Penicillamine and zinc be given together?

Answer 465

NO you idiot, their effects negate each other

Question 466

What are alternative second line copper chelating agents?

Answer 466

Choline tetrathiomolybdate Trientene

Question 467

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

Answer 467

``` Hyperbilirubinemia PT/PTT prolongation Hypoalbuminemia Ascites Extent of fibrosis on biopsy ```

Question 468

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

Answer 468

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