GI/Liver Recap

Question 1

Explain the basic/main physiologic functions of the esophagus

Answer 1

Muscular tube to move oral contents into stomach

Receives lubrication from oral cavity

Question 2

Explain the basic/main physiologic functions of the stomach

Answer 2

Chemical breakdown of food via HCl and pepsin (+ small amount of lipase)- this also help to partially sterilize the meal

Physical breakdown of food via gastric motility patterns (mixing and grinding)

Controls release/rate of delivery of meal to the intestines

Question 3

Explain the basic/main physiologic functions of the duodenum

Answer 3

Site of emptying for products of the pancreas and gall bladder for further digestion

“Monitors” the characteristics of the meal to prepare the later GI tract (and negative feedback back to stomach)

Question 4

Explain the basic/main physiologic functions of the pancreas (exocrine only)

Answer 4

Secretes digestive enzymes for a mixed meal (fat, protein, carb)

Amylase (Carb), Lipase (Fat), Proteases- trypsin and chymotrypsin (protein)

Also secretes large amount of bicarbonate to neutralize acid coming from stomach

Question 5

Explain the basic/main physiologic functions of the jejunum

Answer 5

Majority of nutrient absorption- very high surface area

Helps with electrolyte balance

Peristalsis patterns to move food aborally

Question 6

Explain the basic/main physiologic functions of the ileum

Answer 6

Some nutrient absorption but less compared to jejunum

Major site of B12 and bile salt/bile acid absorption

Question 7

Explain the basic/main physiologic functions of the colon

Answer 7

Major site of water reabsorption- goal is to retain contents long enough for water to be absorbed

Large numbers of bacteria- fermentation and some nutrient production/modification

Storage reservoir for waste

Question 8

What are the clinical signs of small bowel diarrhea?

Answer 8

Large volume of feces
Normal or increased frequency
Flatulence, steatorrhea
Melena (tarry, black)
Weight loss
Vomiting may occur

Question 9

What are the clinical signs of large bowel diarrhea?

Answer 9

Small volume of feces
Increased frequency
Mucus in feces
Hematochezia
Tenesmus
Pain or urgency to defecate

Question 10

What is enterohepatic recirculation and why do we care about it?

Answer 10

Products that are filtered by the liver and excreted into bile go into the small intestine, where they are absorbed by the enterocytes and are transported back into the liver.
One bile salt can be re-used about 20 times.
This can prolong the activity of drugs/toxins (particularly lipophilic ones) and lead to repeated damage to the liver or ongoing high blood levels.

Question 11

What are the zones of hepatocytes? How does this apply to histopathology when trying to determine the cause of liver damage?

Answer 11

• Zone 1 (periportal cells)- closest to the portal vein
  — Responsible for the majority of detoxification and secretory functions under normal circumstances
• Zone 2- middle
• Zone 3- closest to the hepatic vein
  — Can be recruited if liver function is compromised

Zonation also impacts susceptibility to injury
—- Zone 3 hepatocytes most sensitive to hypoxia if blood supply is compromised
—- Zone 1 hepatocytes most affected by oxidant injury from reperfusion injury or toxins

Question 12

Explain Phase 1 hepatic conjugation reactions/ how the liver metabolizes drugs.

Answer 12

• Chemically changes drug so more water soluble 🡪 more susceptible to phase II metabolism
• Oxidation, hydrolysis (addition of water), reduction (addition of hydrogen) can occur
• Cytochrome P450 enzymes are responsible for the majority of phase I metabolism
• Phase I metabolites are usually inactive (but can be equally, more, or less active or more toxic than the parent compound)
  —- Can be an important source of drug-induced toxicity

Question 13

Explain Phase 1 hepatic conjugation reactions/ how the liver metabolizes drugs.

Answer 13

• = conjugation– large water-soluble molecule is chemically added to the phase I metabolite or the parent drug 🡪 usually renders drug sufficiently water soluble to be renally excreted
• Most phase II reactions require energy
• Glucuronidation is the most common phase II reaction
• Sulfonation, acetylation, and addition of glutathione are less common phase II reactions
• Phase II metabolites are almost always inactive and are often eliminated in the urine

Question 14

Draw/label the bile ducts from liver to duodenum.

Answer 14

Question 15

Explain the basics of the ammonia/urea cycle

Answer 15

Ammonia (NH3) is produced from AA degradation, mostly in intestines. Most Ammonia is absorbed into portal circulation and brought to the liver. Small amount of ammonia is “protonated” to ammonium ion (NH4), which is trapped in the colon and eliminated in the stool.

In the liver, ammonia is taken up by hepatocytes and enters mitochondria where it is converted to urea. Urea then enters circulation and is excreted by kidneys into the urine.

Question 16

How does lactulose work to reduce ammonia levels? 3 mechanisms

Answer 16

1. Osmotic diuretic (metabolized to smaller molecules that draw water into colon)- physically flush out ammonia
2. Changes pH (more acidic) to lead to ion “trapping” of ammonium ion in the colon so it can not be absorbed
3. Acidification of gut leads to a shift in bacterial flora to less ammoniagenic bacteria (lactobacilli instead of coliform bacteria)

Question 17

What are the other possible mediators/causes of hepatic encephalopathy? Give a brief overview and then list some…

Answer 17

• High ammonia levels PLUS systemic inflammation seems most important, rather than ammonia levels alone.
• Also, high aromatic AA levels, high manganese levels, altered neurotransmitters (higher levels of GABA, lower levels of glutamate, increased endogenous benzos).
• Some other mediators- methionine 🡪 mercaptans, skatoles, indoles, tryptophan, serotonin, tyrosine 🡪 octopamine, phenylalanine 🡪 phenylethylamine, phenol, bile acids

Question 18

Discuss simple starvation.

Answer 18

• Animals use stored carbs, fat, protein to maintain BG and vital fxns
• Fuel usage shifts to primarily fatty acids
• When BG < 120, liver becomes an exporter of glucose via glycogenolysis and gluconeogenesis
• T3 decreases to lower metabolic rate
• Ketones are used as an alternate fuel source for some tissues (muscles, kidney cortex, peripheral nerves, and the brain)
• BG tends to stay normal
• Refeeding formulas should be a balanced mix of nutrients

Question 19

Discuss stressed starvation

Answer 19

• There is concurrent catecholamine, cortisol, and growth hormone release (stress hormones) along with the glycogenolysis/gluconeogenesis
• This suppresses insulin release 🡪 hyperglycemia, increases proteolysis, and increases lipolysis 🡪 marked catabolism (acute/ebb phase)
• Adaptive/Flow phase eventually occurs- increased metabolic rate, nitrogen gain, anabolic phase to rebuild
  —- Fat is the preferred energy fuel during this time, helps to avoid refeeding hyperglycemia, especially in cats

Question 20

Explain the key features of refeeding syndrome and why they occur.

Answer 20

• Serum ion levels are deceptively normal in anorectic patients but once refeeding begins potassium and phosphate shift intracellularly with glucose resulting in hypokalemia and hypophosphatemia

—- Hypokalemia- Potassium moves into cells with refeeding
- Glucose stimulates insulin release -> stimulates Na-K ATPase pump and glycogen synthesis which requires 0.33 mEq K+/g of glycogen

—- Hypophosphatemia- Phosphate moves into cells with refeeding to support the increased production of ATP
- Severe hypophosphatemia, hemolytic anemia and death have occurred within 12 to 72 hours of refeeding

—- Hypomagnesemia
- Low Mg also increases urinary excretion of potassium
- Exacerbates hypokalemia – which is refractory to supplementation until hypomagnesemia is corrected
- Causes hypocalcemia

• Shift to carbohydrate metabolism can increase demand for cofactors such as thiamine 🡺 clinical thiamine deficiency (neuro)
• Can have refeeding hyperglycemia (esp cats)

Question 21

How do you reduce risk of refeeding syndrome?

Answer 21

• Use conservative RER estimate
• Start feeding gradually
• Closely monitor glucose/electrolytes

Question 22

What is the benefit of NG tube over NE tubes?

Answer 22

• NG tube allows suctioning of stomach
• Otherwise similar complication risk and incidence of regurgitation (both are considered equal for feeding purposes)

Question 23

List possible complications of Esophagostomy tube placement

Answer 23

• Bleeding (jugular vein!)
• Nerve damage- Horners, facial nerve paralysis, less likely recurrent laryngeal nerve
• Inadvertant placement into airway
• Infection at placement site
• Dislodgement
• Esophageal or LES irritation 🡪 reflux, regurgitation, nausea
• Anesthetic complications

Question 24

Briefly discuss TPN

Answer 24

= total parenteral nutrition

• Entire nutritional requirement can be provided
• Carbs from Dextrose, Lipids, Amino Acids, and usually vitamins/minerals
• High osmolarity (usually 1000-2000mOsm/L) so requires a dedicated central line

Question 25

Briefly discuss PPN

Answer 25

= Partial or Peripheral parenteral nutrition

• Can provide part of the patient’s nutritional requirement
• Most commonly dextrose + AA solution
• Lower osmolarity potentially, so may be able to be administered peripherally (if < 600mOsm/L) - still should be a dedicated line

Question 26

List at least 9 possible complications/detrimental effects of parenteral nutrition

Answer 26

1. Hypokalemia/hyperkalemia
2. Hypophosphatemia
3. Hyperglycemia
4. Hyperlipidemia- fat emboli
5. Mechanical catheter complications: kinking, migration, obstruction
6. Phlebitis
7. Sepsis from catheter contamination
8. Increased systemic inflammation
9. Increased risk of GI translocation if not using some concurrent enteral nutrition

Question 27

Discuss steps of calculating a TPN mixture

Answer 27

Step 1: Calculate RER (patients do NOT require more than RER)

Step 2: Calculate protein requirement
4-6g/100kcal for dogs, 6-8g/100kcal for cats
1g protein = 4 kcal
Standard 8.5% AA solution = 85mg/ml AA’s

Step 3: Subtract protein calories from total RER to get remaining kcal left…

Step 4: Calculate lipid and carb requirements- typically 50-70% of remaining calories as lipids and 30-50% of remaining calories as dextrose.
50% dextrose = 1.7 kcal/ml
20% lipids = 2.0 kcal/ml

Step 5: Determine total volume of TPN solution to meet full calorie requirements (add up all 3). Determine rate/hr. Adjust volumes/rate if plan is to provide less than full RER.

Step 6: Add vitamins if needed/desired.

Question 28

Calculate a TPN mixture and feeding schedule for:

4 kg cat with pancreatitis and refractory vomiting

Answer 28

RER = 190kcal
7 g/100kcal = 13.3g protein x 4 kcal = 53 kcal from protein
Remainder = 137 kcal
30% from dextrose = 41 kcal = 24ml dextrose
70% from lipids = 96 kcal = 48ml of 20% lipids

13.3g protein = 156ml of 8.5% AA solution

Total = 228ml/day = 9.5ml/hr for full RER
Start at 1/3 RER

Question 29

Calculate a TPN mixture and feeding schedule for:

15kg dog

Answer 29

RER = 520 kcal

5g/100kcal = 26g protein x 4 = 104 cal from protein

Remainder = 416 kcal
50% from dextrose = 208 kcal = 122ml dextrose
50% from lipids = 208 kcal = 104ml of 20% lipids

26g protein = 306ml of 8.5% AA solution

Total = 532ml/day = 22ml/hr for full RER
Start at 1/3 RER