Pancreas & GIT

Question 1

What parts of the pancreas pictured below are apart of the Endocrine pancreas? Exocrine pancreas?

Answer 1

Islet of Langerhaans = endocrine pancreas
Acini and intralobular duct = exocrine pancreas

Question 2

1. What cells makes up the Endocrine pancreas?
2. What do these cells secrete?
3. What do they regulate? Explain why this is important.

Answer 2

Endocrine pancreatic cells located in islets of Langerhans:
* Alpha cells: secrete glucagon
* Beta cells: secrete insulin
* Delta cells: secrete somatostatin
* PP cells: secrete pancreatic polypeptide

These hormones are important for regulating glucose. For Dx diseases of endocrine pancreas, we use insulin levels

Question 3

1. What cells make up the exocrine pancreas?
2. What do these cells produce? What is the purpose of these enzymes produced?

Answer 3

Exocrine pancreas – acinar epithelial cells
* Produces enzymes (such as lipase) to metabolize proteins, lipids, and carbohydrates in the diet

Question 4

Insulin
* Produced by _____ cells
* Insulin is secreted when there is:
1. An _________ in blood glucose
2. _______ acids, ______ acids, and __________ present
* Major target organs insulin effects:
- ______
- ________ muscle
- ________ tissue

Answer 4

Insulin
* Produced by Beta cells
* Stimuli for secretion:
- Elevated blood glucose
- Amino acids, fatty acids, and hormones present
* Major target organs insulin effects:
- Liver
- Skeletal muscle
- Adipose tissue

Question 5

Name the two major disorders associated with abnormalities of islets of Langerhans.

Answer 5

a. Diabetes mellitus
b. Hyperinsulinism (increased levels of insulin)

Question 6

a. Diabetes mellitus
- Most dogs have insulin _________ (DM - type ___)
- Some cats have ___________ insulin WITH peripheral insulin ________ (DM - type __)
b. Diabetes Mellitus Dx:
- What parameters do you look for when Dx a patient with DM? Diagnosed by persistent ________ _________ and _________.
- For Dx:
- Requires ______ glucose measurements
- Many physiologic causes of hyperglycemia that could be transient and are different from DM. These conditions include?

Answer 6

a. Diabetes mellitus
* Most dogs have insulin deficiency (DM - type 1)
* Some cats have increased insulin WITH peripheral insulin resistance (DM - type 2)
* Diagnosed by persistent fasting hyperglycemia and glucosuria (aka increased levels of glucose in the blood and increased levels/presence of glucose in the urine - IMPORTANT)
For Dx:
- Requires repeated glucose measurements
- Many physiologic causes of hyperglycemia that could be transient and are different from DM - IMPORTANT
ØStress (increased levels of glucose [hyperglycemia])
ØPost-prandial (obtaining samples post-prandial –> hyperglycemia)

So if see patient with high BG, check to see if they are stressed or post-prandial

Question 7

a. Diabetes mellitus (DM) other lab findings
* Urinalysis
1. _______ urine – USG often in the gray zone
- b/c ______ effect of _______ (?)
2. MAY HAVE, not always, ______ (?), _______, ________
- Prone to ______
3. MAY also present with _________ if have already undergone __________
- Due to Increased______ _____ metabolism and generation of ______

Answer 7

a. Diabetes mellitus (DM) other lab findings
* Urinalysis
1. Dilute urine – USG often in the gray zone
- b/c Osmotic effect of glucosuria (osmotic diuresis)
2. MAY HAVE, not always, Pyuria (suppurative urine; neutrophils in the urine), hematuria, proteinuria
- Prone to UTIs
3. MAY also present with Ketonuria if have already undergone ketoacidosis
- Due to Increased fatty acid metabolism and generation of ketones

Question 8

What may a Diabetes mellitus (DM) patient have on their chemistry panel?

Answer 8

Diabetes mellitus (DM) other lab findings
* Chemistry panel
1. MAY HAVE Titrational metabolic acidosis whihc is often due to ketoacidosis
- Remember the KLUE acronym! Ketoacidosis, lactic acid, uremic acids, ethylene glycols are differentials that can induce TMA.
2. Electrolyte abnormalities:
- Hyponatremia
- Hypochloremia
- +/- Hypophosphatemia and hypokalemia
3. Increased hepatic and pancreatic enzyme activities
4. +/- Hyperbilirubinemia
5. +/- Hypertriglyceridemia and hypercholesterolemia b/c sugar and glucose levels affect hepatocytes –> cholesterol and TG imbalances.
6. +/- Hyperosmolarity
* Occurs at very high glucose concentrations (>600 mg/dL)

Question 9

Hyperinsulinism
* Insulin levels measured using ___________
* Typically measured in hypoglycemic animals when ___________ is suspected
- Insulinoma – ____-cell neoplasia that causes __________ insulin production
* Interpret results in light of blood glucose concentration
- Hypoglycemic dog should have ____ insulin levels
- BUT If ________ + insulin concentration ____ or _______, this is inappropriate and indicates insulinoma is likely.

Answer 9

Hyperinsulinism
* Insulin levels measured using immunoassays
* Typically measured in hypoglycemic animals when insulinoma is suspected
- Insulinoma – Beta-cell neoplasia that causes excessive insulin production
* Interpret results in light of blood glucose concentration
- Hypoglycemic dog should have low insulin levels
- BUT If hypoglycemic + insulin concentration WRI or elevated, this is inappropriate and indicates insulinoma is likely.

Question 10

Fructosamine - IMPORTANT
* Fructosamine is formed when glucose is _________ linked to amine groups of ______ and other blood ______.
* Concentration is an indicator of BG concentrations during previous __-__ _____. Very reliable measurement giving info about ______-term glucose metabolism than a single BG concentration
* Used to establish a diagnosis of _____ _____ and also to monitor therapy for _____ patients

Fructosamine is a better indicator of ____ concentration. Used to diagnose ____ more often.

Answer 10

Fructosamine - IMPORTANT
* Fructosamine is formed when glucose is irreversibly linked to amine groups of albumin and other blood proteins.
* Concentration is an indicator of BG concentrations during previous 2- 3 weeks. Very reliable measurement giving info about long-term glucose metabolism than a single BG concentration
* Used to establish a diagnosis of diabetes mellitus and also to monitor therapy for diabetic patients

Fructosamine is a better indicator of BG concentration. Used to diagnose DM more often.

Question 11

Fructosamine - IMPORTANT
1. ________ fructosamine = persistent hyperglycemia
- Used to confirm ______ _______ (93% ______ and 86% ______) vs. catecholamine-induced hyperglycemia in _____
- Indicates poor glycemic control in _______ diabetic patients
2. ________ fructosamine = persistent hypoglycemia
- __________
- Can also occur with __________
- Can occur in ____________ cats

Answer 11

Fructosamine - IMPORTANT
1. Increased fructosamine = persistent hyperglycemia
- Used to confirm diabetes mellitus (93% sensitive and 86% specific) vs. catecholamine-induced hyperglycemia in cats
- Indicates poor glycemic control in treated diabetic patients
2. Decreased fructosamine = persistent hypoglycemia
- Insulinoma
- Can also occur with hypoproteinemia
- Can occur in hyperthyroid cats

Question 12

What are the two major disease processes of Exocrine pancreas?

Answer 12

• Two major disease processes of Exocrine pancreas:
  a. Pancreatits
• Inflammation and injury to pancreatic parenchyma
  b. Exocrine pancreatic insufficiency (EPI)
• Due to loss of pancreatic acinar cells –> reduced production of pancreatic enzymes

Question 13

What do we see in Pancreatitis?
A. _____________ of the pancreas
* Varying degrees of concurrent __________, _______, and _______ (spectrum of subclinical to severe disease)

Answer 13

What do we see in Pancreatitis?
A. Inflammation of the pancreas
* Varying degrees of concurrent hemorrhage, necrosis, and edema (spectrum of subclinical to severe disease)

Question 14

What are the clinical signs of Pancreatitis?

Answer 14

B. Clinical signs
* Vomiting/diarrhea
* Fever
* Inappetence
* Weight loss
* +/- abdominal pain

Question 15

What are the possible sequelae of Pancreatitis?

Answer 15

C. Possible sequelae
* Shock
* DIC
* Diabetes mellitus
* Peritonitis
* Obstructive hepatic disease

PODDS

Question 16

Diagnosis of pancreatitis
Can be difficult to confirm antemortem on laboratory tests alone – _________ is the gold standard aka only way we can confirm.
* Pancreatitis is suggested based on elevated _____ and ______ (dogs) aka ________, ______.
* Enzymes produced and stored in pancreatic ______ cells but they can _____ into plasma during pancreatic cellular injury

Answer 16

Diagnosis of pancreatitis
Can be difficult to confirm antemortem on laboratory tests alone – histopathology is the gold standard aka only way we can confirm.
* Pancreatitis is suggested based on elevated lipase and amylase (dogs) aka Hyperlipasemia, hyperamylasemia.
* Enzymes produced and stored in pancreatic acinar cells but they can leak into plasma during pancreatic cellular injury

Question 17

Serum Lipase
* IMPORTANT: Synthesized in _____, ____ and _____; small amounts from _____ tissues
* Degraded by the _______
So if we are suspicious of pancreatitis, and we run a lipase level. It can be _____, but this _______ rule out pancreatitis.

• Hyperlipasemia is __ specific to pancreatitis:
  1. Pancreatitis
• > ___x above the RI with no evidence of _____ then we can be suspicious of pancreatitis.
  2. ________ and _____ disease (_____ GFR)
  3. ______ disease
  4. Pancreatic and hepatic ________

Answer 17

Serum Lipase
* IMPORTANT: Synthesized in pancreas, stomach and liver; small amounts from other tissues
* Degraded by the kidneys
So if we are suspcicious of pancreatiits, and we run a lipase level. It can be normal. THIS DOES NOT rule out pancreatitis.

• Hyperlipasemia is not specific to pancreatitis:
  1. Pancreatitis
• > 3x above the RI with no evidence of azotemia then we can be suspicious of pancreatitis.
  2. Dehydration and renal disease (decreased GFR)
  3. Hepatic disease
  4. Pancreatic and hepatic carcinomas

Question 18

Serum Amylase
* Interpreted ________ to lipase
* Synthesized in ______, ____, or _____ intestine
* Degraded by the ______
* A normal amylase ____ rule out pancreatitis

• Hyperlipasemia is not specific to pancreatitis:
  1. Pancreatitis
• > ___x above the RI; no evidence of _____ = suspicious of pancreatitis
  2. _____ and ____ disease (______ GFR)
• ____ and ___ disease
• _______ and ____ carcinomas

Answer 18

Serum Amylase
* Interpreted similarly to lipase
* Synthesized in pancreas, liver, or small intestine
* Degraded by the kidneys
* A normal amylase does not rule out pancreatitis

• Hyperlipasemia is not specific to pancreatitis
• pancreatitis
• > 3-4x above the RI; no evidence of azotemia = suspicious of pancreatitis
• Dehydration and renal disease (decreased GFR)
• hepatic and GI disease
• pancreatitic and hepatic carcinomas

Question 19

PANCREATIC LIPASE IMMUNOREACTIVITY (PLI) = IMPORTANT
* Measures lipase originating specifically from the ________
* This is the most _____ and ____ test for diagnosing ______ in dogs and cats
- Increased pancreatic lipase with ______ or ________ GFR
- Decreased pancreatic lipase with _____ ______ or _____ ______/___

• Canine (cPLI) and feline (fPLI) available
• Idexx _____ test (normal or abnormal; not _______)
• Idexx (________)
• ___ lab at Texas A&M

Answer 19

PANCREATIC LIPASE IMMUNOREACTIVITY (PLI) = IMPORTANT
* Measures lipase originating specifically from the pancreas
* The most sensitive and specific test for diagnosing pancreatitis in dogs and cats
- Increased pancreatic lipase with pancreatitis or decreased GFR
- Decreased pancreatic lipase with chronic pancreatitis or acinar atrophy/EPI

• Canine (cPLI) and feline (fPLI) available
• Idexx SNAP test (normal or abnormal; not quantitative)
• Idexx (quantitative)
• GI lab at Texas A&M

Question 20

TRYPSIN-LIKE IMMUNOREACTIVITY (TLI)
* Measures trypsinogen that enters ________ from the ________
- Increased levels in circulation in dogs and cats with (______) pancreatitis:
* This test has low _______ which is why we prefer ____ to diagnose pancreatitis in dogs and cats)
* ______ half-life –> will be rapidly _________ and therefore be more likely _______ during an ____ pancreatitis episode.
* Increased TLI with ________ or ________ GFR
* Decreased TLI with ______ pancreatitis or ______ atrophy/____

Answer 20

TRYPSIN-LIKE IMMUNOREACTIVITY (TLI)
* Measures trypsinogen that enters bloodstream from the pancreas
- Increased levels in circulation in dogs and cats with (acute) pancreatitis:
* This test has low sensitivity which is why we prefer PLI to diagnose pancreatitis in dogs and cats)
* Short half-life –> will be rapidly degraded and therefore be more likely elevated during an acute pancreatitis episode.
* Increased TLI with pancreatitis or decreased GFR
* Decreased TLI with chronic pancreatitis or acinar atrophy/EPI

Question 21

LABORATORY FINDINGS SUPPORTIVE OF
PANCREATITIS - IMPORTANT
1. _________ leukogram, +/- concurrent ____
2. ______glycemia
- happening b/c there is ______ insulin production and secretion
3. _______triglyceridemia, _____cholesterolemia
- happening because _______ insulin is ______ of lipoprotein lipases
4. ______ of inflammatory disease
* Non-_______; _______, _______, OR may have signs of:
5. ___________ secondary to vomiting and/or diarrhea (signs of dehydration you can see in your chemical panel or CBC)- IMPORTANT
* Relative ________ (increased ____, ____, ___)
*______proteinemia
* May also have ____-renal _______

Answer 21

LABORATORY FINDINGS SUPPORTIVE OF
PANCREATITIS - IMPORTANT
1. Inflammatory leukogram, +/- concurrent stress
2. Hyperglycemia
- happening b/c there is Decreased insulin production and secretion
3. Hypertriglyceridemia, hypercholesterolemia
- happening because Decreased insulin is inhibiting of lipoprotein lipases
4. Anemia of inflammatory disease
* Non-regenerative; normocytic, normochromic, OR may have signs of:
5. Hemoconcentration secondary to vomiting and/or diarrhea (signs of dehydration you can see in your chemical panel or CBC)- IMPORTANT
* Relative erythrocytosis (increased Hgb, RBC, HCT)
* Hyperproteinemia
* May also have pre-renal azotemia

Question 22

LABORATORY FINDINGS SUPPORTIVE OF
PANCREATITIS - IMPORTANT
1. __________ abnormalities (anorexia, vomiting and/or diarrhea)
- _________ from vomiting likely and diarrhea
- Vomiting is inducing an ____-______ disturbance –> losing ___ –> metabolic _______
2. ________ effusion
- Typically an exudate (meaning ___ cell count and ____)
3. _____calcemia
- Ionized calcium bound to free fatty acids in necrotic fat.
4. Bile duct __________ secondary to pancreatic/duodenal _______
- This will induce elevated ____ and ___, ____________

Answer 22

LABORATORY FINDINGS SUPPORTIVE OF
PANCREATITIS - IMPORTANT
1. Electrolyte abnormalities (anorexia, vomiting and/or diarrhea)
- Hypokalemia from vomiting likely and diarrhea
- Vomiting is inducing an acid-base disturbance –> losing acid –> metabolic alkalosis
2. Peritoneal effusion
- Typically an exudate (meaning high cell count and protein)
3. Hypocalcemia
- Ionized calcium bound to free faIy acids in necrotic fat.
- B/c enzymes released from pancreatic cells –> necrosis of fat around pancreas.
4. Bile duct obstruction secondary to pancreatic/duodenal swelling
- This will induce elevated ALP and GGT, hyperbilirubinemia

Question 23

EXOCRINE PANCREATIC INSUFFICIENCY (EPI)
* _________ _________ dogs and _____-coated ______ are predisposed (_________-mediated ______ of pancreas)
* Commonly due to ______ or ______ episodes of pancreatitis –> ________ of pancreatic tissue
* Animals with this condition will have ________ and subsequent _________
* This leads to Reduced ________ and _______ (4?)

Answer 23

EXOCRINE PANCREATIC INSUFFICIENCY (EPI)
* German Shepherd dogs and rough-coated Collies are predisposed (immune-mediated atrophy of pancreas)
* Commonly due to chronic or recurrent episodes of pancreatitis –> Destruction of pancreatic tissue
* Animals with this condition will have maldigestion and subsequent malabsorption
* This leads to Reduced electrolytes and enzymes (lipase, amylase, trypsin, chymotrypsin)

Question 24

EXOCRINE PANCREATIC INSUFFICIENCY (EPI)
* Serum ____ is the diagnostic test of choice to confirm EPI in dogs and cats - IMPORTANT
* TLI (also PLI) is typically ________ in animals with EPI
- Decreased number of active exocrine pancreatic ____ cells –> ___ trypsinogen
- Dogs with EPI due to immune-mediated destruction typically have ____ TLI than dogs with EPI due to chronic pancreatitis
- Animals must be ______ at least 12 hours before drawing blood for testing
- Typically a mild _______ in TLI following a meal

Answer 24

EXOCRINE PANCREATIC INSUFFICIENCY (EPI)
* Serum TLI is the diagnostic test of choice to confirm EPI in dogs and cats - IMPORTANT
* TLI (also PLI) is typically decreased in animals with EPI
- Decreased number of active exocrine pancreatic acinar cells –> less trypsinogen
- Dogs with EPI due to immune-mediated destruction typically have less TLI than dogs with EPI due to chronic pancreatitis
- Animals must be fasted at least 12 hours before drawing blood for testing
- Typically a mild increase in TLI following a meal

Question 25

What are the clinical signs associated with intestinal malabsorptive disorders?

Answer 25

Similar to signs of maldigestion (pancreatic disorders): * Diarrhea * Weight loss * Steatorrhea

Question 26

COBALAMIN AND FOLATE * Measurements of both can help to further classify GI disorders. Why?

Answer 26

1. Readily available in commercial pet foods so most animals have balanced levels of these. 2. Should be absorbed in the proximal small intestine

Question 27

List the major intestinal malabsorptive disorders:

Answer 27

1. Protein-losing enteropathy (PLE) 2. Small intestinal bacterial overgrowth (SIBO) 3. Exocrine pancreatic insufficiency (EPI)

Question 28

PROTEIN-LOSING ENTEROPATHY (PLE) * Excess protein is being _____ (a LOT) through the ______ and ___ reabsorbed * Major mechanisms: 1. Mucosal _________ 2. ___________ (mainly ectasia/dilation of _______ vessels). Seen in cases of Inflammation, neoplasia, CHF

Answer 28

PROTEIN-LOSING ENTEROPATHY (PLE) * Excess protein is being lost (a LOT) through the intestine and not reabsorbed * Major mechanisms: 1. Mucosal ulceration 2. Lymphangiectasia (mainly ectasia/dilation of lymphatic vessels). Seen in cases of Inflammation, neoplasia, CHF

Question 29

What will you see on laboratory diagnostics in a case of PLE? Laboratory diagnosis

Answer 29

1. Panhypoproteinemia (loss of all proteins) 2. Hypoalbuminemia (loss of albumin from blood) 3. Hypoglobulinemia - Globulins may be WRI or slightly increased if there is concurrent inflammation happening (this is not a rare occurrence). 4. Lymphopenia - Lymph lost into intestinal lumen 5. Hypocholesterolemia 6. Peritoneal effusion * Why? If albumin is lost and we have < 1.0-1.5 in circulation --> decreased oncotic pressure --> effusion develops in patient 7. Hypocobalaminemia and decreased folate concentration - Due to lack of GI absorption. This helps us Dx PLE. 8. Fecal a1-protease inhibitor (a1-PI) concentration - In healthy animals, a-1 protease inhibitor is not present in GI lumen but it will increase in cases of transmural plasma or lymph loss (like it happens in cases of PLE) * Levels can also be increased in disorders causing blood loss into the alimentary tract: - such as cases of Thrombocytopenia, coagulopathies. * Texas A&M GI lab: provides special tubes that are req. for the fecal samples needed to run tests. - 3 fecal samples required in special tubes provided by the lab

Question 30

PLE: Laboratory diagnosis (continued) * Lymphopenia - Lymph lost into intestinal lumen * Hypocholesterolemia * Peritoneal effusion * Why? If albumin is lost and we have < 1.0-1.5 in circulation --> decreased oncotic pressure --> effusion develops in patient g/dL (decreased oncotic pressure)

Question 31

PLE: Laboratory diagnosis (continued) * Hypocobalaminemia and decreased folate concentration - Due to lack of GI absorption. This helps us Dx PLE. * Fecal a1-protease inhibitor (a1-PI) concentration - In healthy animals, a-1 protease inhibitor is not present in GI lumen but it will increase in cases of transmural plasma or lymph loss (like it happens in cases of PLE) * Levels can also be increased in disorders causing blood loss into the alimentary tract: - such as cases of Thrombocytopenia, coagulopathies. * Texas A&M GI lab: provides special tubes that are req. for the fecal samples needed to run tests. - 3 fecal samples required in special tubes provided by the lab

Question 32

SMALL INTESTINAL BACTERIAL OVERGROWTH (SIBO) * Overgrowth of bacteria in the ____ and ______ --> _________ * ________ _______ dogs predisposed * Could be Primary (idiopathic) * Or Secondary to conditions such as?

Answer 32

SMALL INTESTINAL BACTERIAL OVERGROWTH (SIBO) * Overgrowth of bacteria in the duodenum and jejunum --> malabsorption * German Shepherds predisposed * Could be Primary (idiopathic) * Or Secondary to conditions such as: 1. EPI 2. IBD 3. Intestinal stagnation (ileus) 4. Intestinal obstruction 5. Lymphoma

Question 33

What lab diagnostics would you see in a case of SIBO?

Answer 33

* Aided by analysis of serum cobalamin (vitamin B12) and folate concentrations - Cobalamin is typically decreased; folate is typically increased - “Bacteria consume cobalamin and fart folate” Animals with SIBO have a lot of flatulence.

Question 34

EXOCRINE PANCREATIC INSUFFICIENCY (EPI) * Will often have ____________ due to secondary SIBO * Often there is an _________ folate concentration due to Impaired ________ secretion from the pancreas --> _______ intraluminal pH --> consequence is ________ folate absorption * This is why this condition may have +/- concurrent SIBO

Answer 34

EXOCRINE PANCREATIC INSUFFICIENCY (EPI) * Will often have hypocobalaminemia due to secondary SIBO * Often there is an increased folate concentration due to Impaired bicarbonate secretion from the pancreas --> reduced intraluminal pH --> consequence is enhanced folate absorption * This is why this condition may have +/- concurrent SIBO

Question 35

List the causes of Hypercobalaminemia.

Answer 35

* Vitamin supplementation (via oral or parenteral) * Release from damaged hepatocytes b/c the hepatocytes Store cobalamin within them.

Question 36

1. Describe and discuss the significant biochemistry a. List 2 differential for the glucose change b. Can you explain the change of the Urea? c. Was there something about the sample that could interfere with spectrophotometry and which analytes will be affected? d. How would you interpret the Albumin levels? e. What is your evaluation of the lipids in this patient? f. What about the liver enzymes? What is your interpretation ? Is there hepatocellular injury or cholestasis? 2. Describe and discuss the significant urinalysis findings a. what are the most remarkable changes? b. what would you say about the glucose in urine and what should you compare it in the biochemical profile? 3. Based on the short Hx and lab results, What is the most likely disease in this Dog? 4. What further tests would you recommend and why?

Question 37

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