GI / liver - physiology / pathophysiology / Nutrition Flashcards
General causes of abdominal pain
Distention of a hollow viscus or organ capsule
Ischemia
Traction
Inflammation secondary to a variety of causes
If left untreated any of these causes can result in necrosis of tissue and loss of function
Examples of causes of abdominal pain based on signalment
Old intact male - painful prostate
Intact female with pyometra - uterine rupture and secondary septic peritonitis
Young adult GSD - EPI - predisposed to mesenteric volvulus
Cats - string foreign bodies
Middle-aged, obese female dogs - acute pancreatitis
What is a more sensitive indicator of acute blood loss in dogs, PCV or TP?
TS due to splenic contraction increasing PCV
Most common causes of hemorrhage in dogs with acute conditions of the abdomen?
Splenic rupture (normally secondary to neoplasia)
Severe hemorrhage (from GI ulceration)
Most common causes of hemoabdomen in cats
Nonneoplastic conditions - 54%
Abdominal neoplasia - 46%
Why is BG increased in dogs with extreme hypovolemia?
- Rarely more than 200mg/dL
- Suspected due to the effects of the catecholamines on glycogenolysis and gluconeogenesis
Why can BG be increased in cats?
- Stress
- Diabetes
How low the BG levels are normally with sepsis?
Between the 40-60mg/dL range
Hypoadrenocorticism may also be a cause of hypoglycemia
How many PLT per oil immersion field in normal dogs?
8 to 15 PLT
Each PLT in a monolayer = 15K PLT /uL
If there are >2-3 PLT per field, unlikely the bleeding is strictly from thrombocytopenia
Signs of RBC morphology changes on smear
- Anisocytosis, macrocytosis and polychromatic -> regeneration
- Schistocytes or fragments of RBCs -> suggests DIC
- Heinz bodies -> often seen in systemically ill cats
T/F - The absence of leukocytosis or a L shift rules out an inflammatory or infectious process
False - leukopenia can be due to decreased production or sequestration of WBCs, a viral infection like parvovirus or the use of immunosuppressive drugs.
Assessment of retroperitoneal space in xray
Loss of detail of the kidneys, a “streaky” appearance, or dissension of the retroperitoneal space suggests fluid accumulation, a space-occupying mass or sublumbar lymphadenopathy.
Where is free gas most commonly detected and which xray view is best to detect it
Between the stomach / liver and the diaphragm on the lateral radiography.
A horizontal beam with the patient in left lateral recumbency and focused on the non-dependent area can increase sensitivity for identifying free gas
Causes of large volume of free gas in peritoneum
Pneumocystography of ruptured bladder
Ruptured vagina
Recent abdominal surgery
Ruptured GDV
Pneumoperitoneography
Extension of pneumomediastinum - most often associated with pneumoretroperitoneum, but pneumoperitoneum can happen in rare occasions
Causes of small free gas in peritoneal space
GI rupture
Infection with gas-forming organism
Gas in GB wall, liver or spleen - most often Clostridia spp.
Xray - measurements to suspect GI obstruction in dogs and cats
Dogs:
- Normal SI diameter - 2-3 x width of a rib, or less than the width of an intercostal space
- All small bowel loops should have same diameter
- Abnormal for one segment to be >50% larger than other portions
Cat:
- SI should not exceed twice the height of the central portion of L4 vertebral body
- Or should not be > 12mm
What can happen if we give barium and there is a GI perforation?
Severe intraperitoneal inflammation and granuloma formation - problem can be minimized if abdominal surgery w/ peritoneal lavage is done immediately.
Upper GI contrast w/ barium not contraindicated to dx GI perforation, as surgery is the treatment.
Causes of loss of abdominal detail on plain abdominal radiographs
Lack of fat in abdomen (puppies vs very thin animal)
Free abdominal fluid
Pancreatitis
Large mass
Carcinomatosis
If we suspect free abdominal fluid but cannot be obtained, what else can we do?
Diagnostic peritoneal lavage
What can we measure in ff based in different suspicions of conditions?
- Creatinine + K if we suspect urinary tract leakage
- Glucose / lactate - septic abdomen (glucose > 20mg/dL compared to blood, and lactate > 2mmol/L compared to blood, both 100% sensitive and specific for dx of septic abdomen in DOGS)
- Bilirubin - bile peritonitis
Pure transudate
Clear
TP <2.5g/dL
Cell count < 500 cells / uL
Common causes of pure transudate in abdomen: hypoalbuminemia and portal venous obstruction
Modified transudate
Serous to serosanguinous
TP 2.5-5g/dL
Cell count 300 - 5500 cells / uL
Causes: passive congestion of liver and viscera and impaired lymphatic drainage - R sided CHF, dirofilariasis, neoplasia and liver dz.
Exudate
Cloudy
TP > 3g/dL
Cell count > 5000-7000 cells / uL
Predominant type cell is neutrophil
Can be septic or non septic
If septic - intra and extracellular bacteria
Indications of immediate abdominal surgery
Abdominal wall perforation
Septic peritonitis
Persistent abdominal hemorrhage
Intestinal obstruction
Intestinal FB causing pain / obstruction
Uroperitoneum
Free abdominal gas (not associated with previous sx, pneumomediastinum or invasive procedures)
Abdominal abscess
Ischemic bowel
GDV
Mesenteric volvulus
Bile peritonitis
How severe can pancreatitis be?
From mild and self-limiting to severe fulminant disease with extensive necrosis, systemic inflammation and/or sepsis, multi organ failure and death
Other complications in moderately severe (MSAP) and severe acute pancreatitis (SAP)?
May include local complications - acute peri pancreatic fluid collection, acute necrotic collection, pancreatic pseudocyst, or walled-off necrosis
Is there a veterinary accepted classification for pancreatitis?
No
Most cases of acute pancreatitis in humans are due to? And in dogs and cats?
Alcohol exposure or biliary calculi
Idiopathic
Pancreatitis pathophysiology
Involves intrapancreatic activation of digestive enzymes with resultant pancreatic auto digestion:
- Initial events within the acing cell -> abnormal fusion of normally segregated lysosomes with zymogen granules (inactive forms of pancreatic enzymes)
- That leads to premature activation of trypsinogen to trypsin (may involve changes in signal transduction, intracellular pH and increases in intracellular iCa)
- Trypsin in then activates other proenzymes - sets a cascade of local and systemic effects that are responsible for the clinical manifestations of AP.
- Local ischemia, phospholipase A2 and ROS -> disrupt cell membranes -> pancreatic hemorrhage and necrosis, increased capillary permeability and initiation of arachidonic acid cascade
- Elastase can cause increased vascular permeability -> degrades elastin in vessel walls.
- Phospholipase A2 degrades surfactant -> promotes development of pulmonary edema, ALI, ARDS.
- Trypsin may activate the complement cascade -> influx of inflammatory cells and production of cytokines and more ROS.
- Trypsin can activate the kallikrein-Kinin system -> results in vasodilation, hypotension and possible AKI
- Trypsin can activate the coagulation and fibrinolytic pathways -> microvascular thromboses and DIC.
- Local inflammation and increased vascular permeability -> may cause massive fluid losses -> compromises perfusion -> further inflammation -> vicious cycle that ends in SIRS and MODS.
What patients are at increased risk to develop fatal SAP? And which breeds?
Dogs middle age or older
Overweight
Hx of prior or recurrent GI disturbances
Hx of concurrent endocrinopathies (hypothyroidism, Cushing’s, DM)
Yorkies, Mini Schnauzers and other terrier breeds
What are common clinical findings in cats with AP?
Lethargy, anorexia and dehydration. Vomiting and abdominal pain is less common than in dogs. Icterus and pallor often noted.
Concurrent dz in cats w/ pancreatitis?
Hepatic lipidosis
IBD
Interstitial nephritis or other kidney dz
DM
Cholangitis / cholangiohepatitis
What are signs of systemic complications that dogs and cats might present with MSAP?
Dyspnea, bleeding disorders, arrhythmias, oliguria, shock and collapse
T/F - The absence of specific findings in any diagnostic test rules out the possibility of acute pancreatitis
False
Initial hemogram - potential RBCs changes in AP?
Ht and RBCs might be normal
Anemia can be seen, especially in cats
Increased Ht reflecting hemoconcentration and dehydration - in humans: associated with more severe disease.
Why can hepatic enzymes and Tbil be increased in AP?
May reflect some ischemic and/or toxic hepatocellular injury or concurrent hepatobiliary disease.
Calcium and pancreatitis
- Hypercalcemia has been reported in some dogs with AP
- Mild to moderate hypocalcemia and hypomagnesemia are not uncommon - suspected as a result of pancreatic and peri pancreatic fat saponification (multiple mechanisms proposed)
- Ionized hypocalcemia appears to be common in cats with AP - associated with poorer outcome.
Are increased activities of serum lipase and amylase useful to dx pancreatitis?
No. Elevations may occur also from extra pancreatic sources (azotemia, glucocorticoid administration). Often WNL in animals with confirmed pancreatitis, particularly cats.
TLI and pancreatitis
Elevations in trypsin-like immunoreactivity - may suggest pancreatitis, but can also occur with azotemia and with GI disease in cats.
TLI might be normal in some patients with AP.
Might have some clinical utility in cats if combined with imaging, but not considered useful in dogs.
Pancreatic elastase-1 (cPE-1) in pancreatitis
- Elevations demonstrated in dogs with AP.
- May be useful for dx of SAP, but not for mild AP.
- Further evaluation needed
Species-specific pancreatic lipase immunoreactivity (fPLI, cPLI) and pancreatitis
- Data suggests PLI is sensitive and specific for AP in spontaneous cases of AP in both species.
- Does not appear to be affected by renal disease or steroids administration.
- PLI currently the most useful marker available for dx of AP.
Radiographic signs of pancreatitis
- Increased density and loss of detail in the right cranial abdomen
- Displacement of the descending duodenum to the right with widening of the angle between the proximal duodenum and the pylorus
- Caudal displacement of transverse colon
- Gastric distension and static gas pattern - suggestive of ileum.
Cats: nonspecific - decreased peritoneal detail most commonly. Hepatomegaly, mass effect in cranial abdomen and SI dilation have been reported.
US for pancreatitis
- Useful to monitor progression
- Pancreas may appear enlarged and hypoechoic - suggestive of edema / necrosis
- Pancreatic duct dilation, thromboses and organ infarcts may also be detected.
- FNA of pancreatic necrosis done routinely in humans to identify infected pancreatic necrosis.
Is CT sensitive to dx pancreatitis?
- In humans contrast enhanced CT is gold standard
- Preliminary data suggests not very sensitive for dx of AP in cats.
Is pancreatic FNA useful to diagnose pancreatitis?
No. Is more valuable to evaluate local complications, infected necrosis and to monitor disease progression than to diagnose AP per se.
Does histopathological findings on pancreas correlate with clinical severity?
No
Additional dx for pancreatitis
- UA
- U culture and susceptibility
- Chest xray
- Venous / ABG
- Lactate and iCa
- Coagulation profile - coagulation abnormalities reflecting DIC and thromboses appear to be common in dogs and cats with SAP.
- If fluid accumulation (wherever) - fluid analysis, cytology and culture. Serial cytologies might be useful to monitor disease progression.
- Recent studies - elevated cPLI and lipase activity in peritoneal fluid may support a diagnosis of AP in dogs.
Human pancreatitis-specific scoring systems?
- Ranson’s Criteria
- The Glasgow (Imrie) score
- Balthazar’s CT index
- Bedside Index for Severity in AP (BISAP)
- Harmless AP Score (HAPS)
Most promising human biomarkers evaluated in pancreatitis
- Trypsinogen activation peptides (TAP)
- Carboxypeptidase
- C-reactive protein (CRP)
- IL 6, IL 8
- Neutrophil elastase
CRP currently the best established and most widely available marker for predicting severity.
Markers for pancreatitis in dogs?
Increases in CRP and urinary TAP-to-creatinine ratio have been demonstrated in dogs with spontaneous AP - further evaluation needed.
Treatment of pancreatitis (general guidelines)
- Elimination of any potential underlying cause
- Early aggressive intervention against systemic complications
- Symptomatic and supportive therapy
1) Resuscitation, fluid therapy and monitoring
2) Pain management
3) Nutrition
4) Additional and supportive therapy
5) +/- antibiotic therapy
6) Surgery?
Have the type and rate of fluid admin been assessed in veterinary medicine for patients with AP?
No. In humans, a study suggested resuscitation with LRS reduced systemic inflammation at 24h when compared with normal saline - no differences in outcomes tho.
Fluids for pancreatitis patients
- Maintenance fluid requirements might be pretty high due to massive ongoing losses (vomiting, third space into peritoneum, GI tract and interstitial)
- Assess lytes - K supplementation usually needed.
- Concurrent use of a synthetic colloid is often necessary for patients with SAP
Patients with pancreatitis and hypocalcemia, when should calcium be supplemented?
Only if signs of tetany are observed, because of the potential for exacerbation of free radical production and cellular injury
Pancreatitis and pressors
- Patients that are hypotensive despite adequate volume replacement will need pressors.
- In experimental feline models of AP - low-dose dopamine (5mcg/kg/min) showed to reduce the degree of pancreatic inflammation by decreasing microvascular permeability - further research.
FFP and pancreatitis
- Usually advocated as a source of alpha2-macroglobulins (important protease inhibitors that help clear activated circulating proteases)
- Studies in human - no improvement in morbidity or outcome with the use of plasma.
- Retrospective study in dogs - no benefit.
- May be indicated to treat coagulopathies, including DIC.
Pain management in pancreatitis
- Aggressive analgesia indicated in all patients, even the ones that do not show pain.
- Will help decrease levels of stress hormones, improve ventilation and improve GI motility if ileus is in part due to pain.
- Systemic opioids main therapy.
- Can be supplemented with low-dose ketamine or lidocaine.
- Low-dose lidocaine - promotility effects - can be beneficial if severe ileum.
- Epidural and intraperitoneal analgesia can be used in select patients.
- NSAIDs - not recommended unless patient is hemodynamically stable, non azotemic and well perfused.
Nutrition and pancreatitis
- Ideally early enteral nutrition - within 24h of hospitalization, especially with MSAP and SAP.
- Improves gut mucosal structure and function and decreases bacterial translocation - attenuating stimuli for propagation of SIRS.
- Enteral: less complications than parenteral (infection, decreased risk of MODS, decreased mortality rates, less expense, shorter hospitalization)
- Jejunostomy tube - bypasses the pancreas - not sure how exocrine pancreatic function is altered (is it beneficial to bypass?), requires general anesthesia - other routes chosen.
- Nasogastric / esophagostomy tubes - especially in cats with risk of hepatic lipidosis
- If patient has severe ileus or vomiting - tickle feeding
- Supplemental total or partial PN should be considered if nutritional requirements cannot be met with enteral nutrition alone.
- Ideal composition unknown - recommended supplementation with glutamine.
- Cats, especially those with concurrent GI tract dz - Vet B12 supplementation
- Avoid overfeeding.
- Early enteral nutrition also recommended for mild AP.
Additional therapies in pancreatitis
- Might not influence outcome but help with patient comfort
- GI protectants
- Thermal support
- Physical therapy
- Antiemetics and prokinetics useful for patients that vomit and with ileus
- Dopaminergic antagonists (metoclopramide) may be less effective or should be avoided.
- Intermittent NG decompression can help with severe ileus.
- Treatment of concurrent dz (DKA, DM)
Antibiotics and pancreatitis
- Prophylactic not recommended in most cases -> risk of inducing resistant bacterial strains and fungal infections.
- In vet medicine incidence of pancreatic / peri pancreatic infection unknown (humans about 30%).
- Empiric antibiotic therapy might be reasonable for patients that do not respond to other therapy, or for those that respond but then deteriorate - monitor serial US and FNA of pancreatic areas to look for signs of infection.
- Development of infection in urinary tract / respiratory tract can occur.
Is surgery indicated in AP cases?
- Surgery is not indicated in most cases involving sterile pancreatic necrosis
- Debridement and/or drainage is indicated in patients with infected necrosis
- Surgery also recommended if extra hepatic biliary obstruction is present (EHBO), and those who continue to deteriorate despite aggressive medical therapy.
Outcome in pancreatitis patients?
- Patients that survive might be normal, or continue to have episodic flare-ups.
- Those that relapse - monitor for pancreatic pseudocysts, walled-off necrosis or EHBO
- Some patients might develop DM, chronic pancreatitis and/or EPI.
What are the 2 main histological types of cholecystitis in dogs and cats?
Neutrophilic and lymphoplasmacytic, follicular cholecystitis
Describe patient signalment for cholecystitis
Any age, breed or sex.
Shetland Sheepdogs are predisposed to gallbladder disorders, and mucocele in particular.
Cocker Spaniels also. No mention of Terriers¿?
Cholecystitis - clinical signs
Very nonspecific - anorexia, lethargy, vomiting and diarrhea.
Cholecystitis - common BW abnormalities
Hematology: inflammatory leukogram - leukocytosis and neutrophilic
Biochemistry:
Increased ALT, AST, ALP and GGT.
If biliary obstruction / cholestasis - increases in cholesterol and bilirubin
AUS is recommended based on clinical findings
General causes of cholecystitis in dogs and cats
Infectious - bacteria, parasites
Obstruction
GB mucocele
GB infarction
What are the most common bacteria isolated from dogs and cats with cholecystitis
Typically from enteric origin:
E. coli
Enterococcus app.
Bacteroides spp.
Clostridium spp.
Pathogenesis of bacterial cholecystitis
- Underlying cause of bacterial infection in the bile is unknown.
- Bacterial colonization of bile may occur via reflux of duodenal bacteria or by hematogenous spread through the portal vasculature.
- Presence within the bile of bacteria + increased biliary pressure due to obstructive process leads to infection of bile and cholecystitis.
AUS findings with cholecystitis
- Hyper or hypo echoic thickening of the GB wall
- Distention of the GB and/or cystic duct
- Echogenic bile
- Presence of gas within the lumen or wall of the GB - emphysematous cholecystitis -> gas producing bacteria - E. coli and Clostridium spp.
Necrotizing cholecysttis
3 types:
- Type I - areas of necrosis w/o GB rupture
- Type II - acute inflammation w/ rupture
- Type III - chronic inflammation with adhesions and/or fistulae to adjacent organs.
Majority of dogs w/ necrotizing CC have had bacterial infection, although it can occur without infection, secondary to GB mucocele.
GB rupture
- Prompt surgical intervention
- Imaging: ff within the GB fossa or generalized through the abdomen, echogenic reaction in the pericholecystic region. Decreased peritoneal detail on abdominal radiographs.
- Effusion: bilirubin >2x serum bilirubin - bile peritonitis.
- High preoperative mortality, overall long-term survival 61% to 82% for dogs w/ bacterial cholecystitis undergoing surgery.
Medical management of cholecystitis
- Antimicriobial selection based on culture and susceptibility of bile
- Empiric - directed at aerobic and anaerobic enteric flora.
Parasitic cholecystitis
- Most common in cats, rarely in dogs
- Most common feline parasites - Platynosomum continuum and Amphimerus pseudofelineus
- Both similar life cycle: eggs ingested by a land snail -> second intermediate host (fish/arthropod) - cats ingest the second intermediate host.
- Adult worms develop in GB or bile ducts - various degrees of illness, from asymptomatic to complete bile duct obstruction.
- Tx: praziquantel
- Grave prognosis for severe infestations, not reported long-term survival
Timeline of events when there is a GB obstruction
- Any obstruction to bile flow from the GB will lead to cholecystitis
- Complete EHBDO -> dilation of GB and cystic duct within 24h, and dilation of intrahepatic bile ducts within 5 to 7 days.
Hepatic changes with chronic GB obstruction
- Hepatocyte necrosis
- Cholangitis
- Periportal fibrosis
Potential causes of EHBDO
Choleliths and GB obstruction
- Uncommonly associated with cholecystitis in dogs and cats
- Can cause cholecystitis by mechanical trauma or duct obstruction.
- Can develop secondary to cholecystitis - increased mucus production and decreased GB motility, associated with inflammation, may promote cholelith formation.
- Mainly composed of calcium carbonate and bilirubin pigments (vs cholesterol stones in humans).
- Radiopaque choleliths - only in 48% of dogs and 83% cats with symptomatic cholecystitis
- AUS preferred imaging modality to identify choleliths.
When is surgery indicated with choleliths?
- It might be an incidental finding, but if there is concurrent presence of bile duct dissension and/or clinical signs and clinicopathologic evidence of cholecystitis.
- Cholecystectomy is the treatment of choice.
- Samples of liver, GB and bile should be obtained for histopathology, cytology and culture (anaerobic and aerobic).
Prognosis for cholecystectomy associated with choleliths in dogs and cats
- Depends on the absence or presence of concurrent disease, bacterial infection and/or GB rupture.
- Reported long-term survival after surgery: 78% cats, 41% for dogs.
Pathophysiology of GB mucocele
- Accumulation of thick, mucin-laden bile within the GB and bile ducts, leading to different degrees of obstruction to bile flow.
- Progressive dissension of the GB can lead to ischemic necrosis of the walk and resultant GB rupture.
- It is thought to be the result from a combination of increased mucin production and decreased GB motility.
Signalment and genetic components of GB mucocele
- Middle age to older (median age of 9 to 11 years) dogs, but younger as 3 years old have been reported.
- Shetland Sheepdogs, Cocker Spaniels and Miniature Schnauzers appears to be at increased risk.
- Shetland Sheepdogs and other breeds -> insertion mutation on the ABCB4 gene (encodes for a protein that translocates phosphatidylcholine from hepatocyte to biliary canal) has been associated with mucocele formation.
Conditions associated /increased risk for GB mucocele
- Dyslipidemias
- Glucocorticoids excess - Cushing’s dogs significantly increased risk.
Biochemistry changes associated with GB mucocele
- Increased ALT, AST, GGT and ALP
- Hypercholesterolemia
- Hyperbilirubinemia
AUS and GB mucocele
- Echogenic, non mobile material fills the distended GB in either a stellate (kiwi) or finely striated pattern, often with a hypo echoic rim along the wall.
- Non pathologic bile sludge - moves when changing patient’s position - not with a mucocele.
- Fluid in GB fossa, generalized or echogenic reaction in the pericholecystic region suggests possible GB rupture.
Is bacterial infection common in patients with GB mucocele?
No. It has been reported in <10% of the cases, with the exception of positive aerobic cultures in 6/9 cases in one study.
Preferred treatment for GB mucocele
- Cholecystectomy.
- Cholecystotomy not recommended - underlying cause of mucocele formation is not removed and there might be areas of GB wall necrosis, even in the absence of GB rupture.
- Common bile duct must be catheterized to be sure it is patent.
- Excised GB has to be sent to histopathology, anaerobic and anaerobic culture.Liver biopsies are recommended to assess underlying disease.
Medical management of GB mucocele
- It can be considered in asymptomatic dogs
- Ursodeoxycholic acid (UDCA) - choleresis, immunomodulatory properties, may decrease mucin secretion and may improve GB motility. 10-15mg/kg PO q12-24h.
- S-adenosylmethionine (SAMe) - hepatoprotective effects - glutathione precursor and antioxidant, and may have choleretic effects. Given on an empty stomach for better absorption, 20-40mg/kg PO q24h.
- Antibiotics - aimed at enteric flora to treat potential cholangitis, although bacterial infection is uncommon.
- Medical management assumes a risk of necrotizing cholecystitis and GB rupture, should only be undertaken under close monitoring and client communication.
Prognosis of GB mucocele
- Guarded
- With medical management - unknown
- With surgery - high perioperative mortality of 20% to 40%.
- Dogs surviving the immediate postoperative period appear to have good long-term survival.
- Septic bile peritonitis worse prognosis than sterile bile peritonitis.
GB infarction
- Uncommon condition - described in a small group of 12 dogs.
- Can mimic cholecystitis and result in GB rupture
- Diagnosis confirmed on histopathology post surgery.
- Clinical signs and clinicopathological changes same as cholecystitis / GB obst. / rupture.
- GB rupture present in 50% of the cases
- Bacterial infection documented in 25% of cases - enteric organisms (E. coli and Clostridium).
Postoperative survival rate of 67% - Thrombi identified in artery supplying the GB, evidence of distant thrombosis of the spleen - suspected hyper coagulable state - one dog was treated for Cushing’s and another one for hypothyroidism.
What is the function of the interstitial cells of Cajal
they act as electrical pacemaker of the smooth muscle cells in the GI. They generate the slow wave activity in the GI.
Difference between spike potentials in the smooth muscle compared to nerve fibers
i. Due to calcium-sodium channels as opposed to the sodium channels of nerves
ii. Slower to open-close, accounting for the longer duration of its action potential
List Factors resulting in depolarization of the membrane of GI smooth muscle cells
- Stretching of the muscle
- Stimulation by Ach or the parasympathetic nerves that secrete Ach.
- Stimulation by various GI hormones
List Factors resulting in hyperpolarization of the membrane of GI smooth muscle cells
- NE and epinephrine
- Stimulation of the sympathetic nerves that secrete these catecholamines
What are the two plexuses of the enteric nervous system and their functions
- Myenteric plexus (Auerbach’s plexus)- found between the longitudinal and circular muscle layers and is mostly responsible for GI movements
* When stimulated causes:
a. Increased tonic contraction of the gut wall
b. Increased intensity of the rhythmical contractions
c. Increased rate of the rhythm of contraction
d. Increased rate of velocity of conduction of excitatory waves along the gut wall, causing more rapid movement of the peristaltic waves
* Also releases inhibitory substances that inhibit the sphincter muscles that impede the movement of food (pyloric sphincter, ileocecal valve sphincter, lower esophageal sphicter) - Submucosal plexus (Meissner plexus)- lies in the submucosa
* control Intestinal secretion, absorption, and local contraction of the submucosa muscle.
“The Parasympathetic innervation of the GI tract is Divided into:
a. ___________division is via the ________ nerve and provide innervation to the esophagus, stomach, pancreas, and down to the proximal large intestine.
b. The _________division is via the _______ nerve and innervates the distal half of the large intestine”
Cranial division –> vagus
Sacral division –> pelvic nerve
Give examples of reflexes from the gut to the spinal cord or brainstem and then back to the GI tract.
a. Vagus nerve control of gastric motor and secretory function
b. Pain reflexes which inhibit the GI tract
c. Reflexes that result in muscle contraction to facilitate defecation
Fill the table for GI hormones/ stimuli for secretion / site of secretion / actions
*gastrin
* cholecystokinin
* secretin
* gastric inhibitory peptide
* motilin
List mechanisms of increased blood flow in the GI tract
a. Release of vasodilator substances
i. Cholecystokinin
ii. VIP
iii. Gastrin
iv. Secretin
b. Release of kinins from the gut wall
i. Bradykinin
ii. Kallidin
c. Decreased oxygen concentration
i. Secondary to an increased metabolic rate and may result in the release of adenosin, a well-known vasodilator
T/F - The venous and arterial blood flow in the villi is in opposite directions and the arteries and veins are in close approximation. Most of the arterioler oxygen diffuses directly into the venules without reaching the tip of the villus. Conditions that result in diminished blood flow to the gut (hypotension) can result in ischemic death of the villus tip and a greatly diminished GI absorptive capacity.
TRUE
_______ predominately stimulate the release of hormones that inhibit gastric flow and allow the _______, which normally is slowly digested, to be digested
Fats
Fat
______ is released in response to the presence of fats in the chyme. This hormone inhibitis gastric emptyng and is released from the mucosa of the _______ and __________ in response to fat and proteins in the chyme
CCK
Duodenum and jejunum
Gastrin, CCK, insulin, and serotonin stimulate motility whereas _____________and __________ inhibit it.
secretin and glucagon
what is the migrating motor complex
Occurs hours after a meal or during the fasting state and recurs approximately every 90 minutes. The migrating complex causes peristaltic waves to “sweep” from the stomach down towards the colon, removing any gastric secretions or chyme
Explain the dual effect of sympathetic stimulation in the GI tract
If acting by itself, stimulation usually causes a very mild increase in secretion. However, if parasympathetic stimulation is causing the release of copious amount of secretions, sympathetic stimulation will decrease secretion secondary to the diminished blood flow to the glands
T/F - Saliva is rich in bicarbonate and potassium and low in sodium and chloride
TRUE
peptic (or chief) cells secrete ______________
Pepsinogen
parietal (or oxyntic) cells secrete:
HCl and intrinsic factor
The stomach mucosa has two main types of tubular glands:__________- what do they secrete?
- gastric (oxyntic) acid-forming glands –> 1. Secrete hydrochloric acid, pepsinogen, intrinsic factor, and mucus
- Pyloric glands –> 1. Secrete mucus, some pepsinogen, and most importantly, gastrin.
T/F pepsinogen is secreted as an inactive molecule which becomes activated when in the presence of hydrochloric acid
TRUE
What is the function of the intrinsic factor, where is produced and what happens when is not produced?
- Secreted by the parietal cells with hydrochloric acid
- Necessary for the absorption of vitamin B12 in the ileum
- Failure to secrete intrinsic factor can result in pernicious anemia, failure of RBC maturation in the absence of Vit B12 stimulation of the bone marrow
List 3 factors that stimulate gastric secretion
Ach
gastrin
histamine
Both the vagus nerve and local reflexes, in addition to causing direct secretion of hydrocholric acid, also cause the release of gastrin. Secreted by ____________ in the pyloric glands
gastrin cells (G cells)
T/F When the actions of histamine are blocked, the effectiveness of gastrin and Ach in stimulating acid secretion is unchanged
FALSE - they are greatly diminished
The gastrin mechanism for secreting hydrochloric acid becomes blocked when the pH falls to below:________. Why?
<3
- High acidity stimulates release of somatostatine from delta cells, which in turn, depresses gastrin secretion by G cells
- Acid causes an inhibitory nervous reflex that inhibits gastrin secretion
The cephalic phase of gastric secretion Is mediated by the _______nerve, and accounts for___% of the gastric secretion durnig a meal
Vagus nerve
30%
What is the enterogastric reflex
Inhibits gastric secretion –> Initiated by distention of the small bowel, presence of acid, presence of protein breakdown products, or irritation of the mucosa.
Mention two important hormones that participate in inhibition of gastric secretions
secretin
glucose-dependend insulinotropic peptide (GIP)
Others –> VIP, somatostatin
List the pancreatic enzymes and their main action
Trypsin and chymotrypsin –> split proteins into peptides
Carboxypolypeptidase –> splits peptides into AA components
Pancreatic amylase –> hydrolyzes starches, glycogen –> forms disaccharides
pancreatic Lipase –> digests fats into fatty acids and monoglycerides
Phospholipase –> splits fatty acids from phospholipids
cholesterol esterase –> hydrolysis of cholesterol esters
Trypsinogen is activated by the enzyme
Enterokinase
pancreatic secretion is stimulated by which hormones:
- Ach- released from the vagus nerve endings and nerve endings of the enteric nervous system
- Cholecystokinin- secreted by duodenal and upper jejunal mucosa in response to the presence of food
- Secretin- secreted by the duodenal and jejunal mucosa in response to acidic chyme
This enzyme is necessary to protect the duodenal mucosa and to provide an appropriate pH for the activity of the digestive enzymes (neutral to slightly alkaline)
secretin
List main functions of Bile salts
*Emulsification of fat so lipases release by pancreas can digest fat
* Transport and absorption of digested fat end products to and through the intestinal mucosal membrane
* Waste product removal –> mainly billirubim and excess cholesterol synthesized by the liver
This enzyme released from I cells mainly in response to fatty foods, causes contraction of the gallbladder and relaxation of the sphincter of Oddi, that guards the exit of the bile duct into the duodenum
Cholecystokinin
The precursor of bile salts is __________, which is converted into various bile acids.
Cholesterol
Approximately____% of the bile salts are reabsorbed by the intestines and taken up by the hepatic sinusoids from the portal blood.
94%
T/F Brunner glands secrete alkaline mucus in the small intestine
TRUE - they secrete mucus in large amounts in response to secretin, parasympathetic stimulation, and tactile/irritating stiimuli.
What is the function of the crypts of Lieberkuhn?
Secretion of the intestinal digestive juices
The crypts of lieberkuhn and the intestinal villi are covered by an epithelium composed of these two main cell types:
Gobblet cells –>secrete mucus
Enterocytes
T/F Hydrolysis is the basic process of digestion
TRUE
Alpha amylase can be found in
Saliva - not in SA
Pancreatic secretions
T/F Disaccharides and small glucose polymers are hydrolyzed to monosaccharides by intestinal epithelial enzymes
TRUE - the disaccharides are: lactose, sucrose, maltose
Disaccharides are combinations of monosaccharides bound to one another by condensation. Explain how they combine
This means that a hydrogen has been removed from one and a hydroxyl ion from the other. These then combine to form water and the two monosaccharides bind where the hydrogen and hydroxyl ion were removed.
Explain the process of hydrolysis for carbohydrates and triglicerides
Carbohydrates –> specific enzymes return the hydrogen and the hydroxyl ions to the polysaccharides and thereby separate the monosaccharides from each other. This is the process of hydrolysis
Triglycerides –> the fat-digesting enzymes returning molecules of water to the triglyceride molecule and thereby splitting the fatty acid molecules away from the glycerol.
In all 3 instances (including proteins), the process of hydrolysis is necessary for digestion, the only difference being the enzymes necessary to promote the reactions of each type of food
T/F - the pH must be alkalinic for pepsin to work effectively.
FALSE - has to be acidic
T/F - One of the most important functions of pepsin is its ability to digest collagen. Collagen is found in large proportion in meat products and, for the enzymes to digest the cellular proteins, it is first necessary that the collagen fibers be digested
TRUE
__________is the process of break the fat globules into small sizes so that the water soluble digestive enzymes can act on the globule surface
Emulsification
T/F the purpose of the bile salts and especially the lecithin is to make the fat globules readily fragmentable by agitation of the small bowel. The emulsification process greatly increases the surface area of the fat globules.
TRUE
T/F Aldosterone greatly enhances the absorption of Na in the intestinal epithelial cells
TRUE - this effect is specially prominent in the colon
T/F calcium absorption is enhanced by –> PTH activated Vit D in the kidneys and the activated Vit D
TRUE
By which mechanism are glucose and amino acids absorbed in the GI?
By a sodium co-transport mechanism
This cells contribute significantly to mucin production in exocrine glands and can account for as many as 25% of the epithelial cells in the distal main pancreatic duct of some species
a. Acinar cells
b. Centroacinar cells
c. Goblet cells
c. Goblet cells
- This could be a finding in a patient with acute pancreatitis
a. Decreased levels of CCK
b. Decreased levels of ACh
c. Increased levels of ACh
d. M3 receptors deficiency
c. Increased levels of Ach
T/F Carbohydrates are potent stimulators of pancreatic secretion
FALSE
T/F - Lipids are poor stimulators of pancreatic enzyme secretion
FALSE
This hormone is released when the duodenal pH is <4.5 in order to stimulate secretion of HCO3 and fluid
a. Secretin
b. ACh
c. Cholecystokinine
Secretin
Mention 3 mechanisms that protect the pancreas from autodigestion:
Digestive proteins are stored in secretory granules as inactive precursors or zymogens
• The secretory granule membrane is impermeable to proteins
• Enzyme inhibitors such as pancreatic trypsin inhibitor, co-packaged in the secretory granule, block the activity of trypsin aberrantly activated within the granule
T/F - Salivary duct cells produce a hypertonic fluid rich in NaCl and poor in KHCO3
TRUE
You received a patient that was referred by his rDVM for surgical removal of a gastrointestinal neoplasia. The rDVM did an abdominal ultrasound but he was unable to determine which intestinal segment was likely to be the origin of this neoplasia. The owners are human physicians and want more details about the future nutritional consequences that this patient will suffer after surgery. Pick the statement that would be false:
a. If the neoplasia is in the ileum, is likely that after surgery the patient could develop Cobalamine and bile acids absorption deficiency and he could need supplementation.
b. If the neoplasia is in the duodenum and a significant part must be removed, a possible post-operative consequence could be development of megaloblastic anemia
c. If a total gastrectomy is necessary, the patient will have severe protein absorption deficiency and his fecal nitrogen excretion will be considerably elevated.
c. If a total gastrectomy is necessary, the patient will have severe protein absorption deficiency and his fecal nitrogen excretion will be considerably elevated (FALSE: Pepsin in the stomach partially digests 10% to 15% of dietary protein Pepsin hydrolysis is not absolutely necessary; patients with either total gastrectomies or pernicious anemia do not have increased fecal nitrogen excretion)
You are suspicious that your patient has a condition know as pernicious anemia, in this condition there is a lack of secretion of _______ and _____. The main etiology associated with this condition is _________. The reason why this patient develop anemia is because there is a lack of ___ that normally is required for _____ absorption in the ileum, which is an essential vitamin for the synthesis of RBCs.
You are suspicious that your patient has a condition know as pernicious anemia, in this condition there is a lack of secretion of _______ and _____(gastric acid and intrinsic factor). The main etiology associated with this condition is _________ (immune-mediated/ abs against parietal cells and IF). The reason why this patient develop anemia is because there is a lack of ___ (IF) that normally is required for _____ (Cobalamin/ vitb12) absorption in the ileum, which is an essential vitamin for the synthesis of RBCs.
These two molecules are released by the duodenal mucosa to complete lipid hydrolysis initiated in the stomach:
a. CCK and gastric inhibitory polypeptide (GIP)
b. ACh and CCK
c. Somatostatine and gastrin
d. VIP and GIP
a. CCK and gastric inhibitory polypeptide (GIP)
- The Fat-soluble vitamins are
a. B12, A, C
b. D, E, B12
c. A, D, E, and K
c. A, D, E, and K
T/F a. Folate deficiency compromises DNA synthesis and cell division, an effect that is most clinically noticeable in the bone marrow, where the turnover of cells is rapid
TRUE
Mg2+ depletion is typically associated with
a. Hyperkalemia
b. Hypocalcemia
c. Hypokalemia
d. Hypercalcemia
b. Hypocalcemia (Mg is necessary for proper secretion of parathyroid hormone)
Describe the direct and indirect pathways of vagal stimulation for gastric H+ secretion. How can you block both pathways?
Direct pathway
* the vagus nerve innervates parietal cells and stimulates H+ secretion directly.
* The neurotransmitter at these synapses is ACh, the receptor on the parietal cells is muscarinic (M3), and the second messengers for M3 and CCK are IP3 and increased intracellular [Ca].
Indirect path
* the vagus nerve innervates G cells and stimulates gastrin secretion, which then stimulates H+ secretion by an endocrine action.
* The neurotransmitter at these synapses is GRP {notACh).
How to block it?
* Atropine (cholinergic muscarinic antagonist) –> blocks the direct pathway (which uses ACh). However, does not inhibit the indirect pathway (which uses GRP as a neurotransmitter)
* Vagotomy eliminates both direct and indirect pathways.
The second messenger for the M3 and CCK receptors in the parietal cell is IP3, but for histamine, the second messenger is___________
cAMP
Explain how prostaglandins inhibit gastric H+ secretion
Prostaglandins inhibit gastric H+ secretion by activating a Gi protein, inhibiting adenylyl cyclase and decreasing cAMP levels.
They also maintain the mucosal barrier and stimulate HC03- secretion, thus protecting the gastric mucosa from the damaging effects of H+
Which one is false regarding the composition of pancreatic secretions:
(1) high volume
(2) virtually the same Na+ and K+ concentrations as plasma.
(3) much higher HC03- concentration than plasma.
(4) same Cl- concentration than plasma.
(5) isotonicity.
(6) pancreatic lipase, amylase, and proteases.
(4) same Cl- concentration than plasma. FALSE. Cl is much lower than plasma
What is the function of the ductal cells of the pancreas?
- Ductal cells modify the initial pancreatic secretion by secreting HC03- and absorbing Cl via a CI–HCO3- exchange mechanism in the luminal membrane.
- secretin acts on the pancreatic ductal cells to increase the HCO3- secretion
- Because the pancreatic ducts are permeable to water, H2o moves into the lumen to make the pancreatic secretion isosmotic
T/F - CCK is secreted by the I cells of the duodenum in response to small peptides, amino acids, and fatty acids in the duodenal lumen. CCK acts on the pancreatic acinar cells to increase enzyme secretion (amylase, lipases, pro teases).
TRUE
What are the primary bile acids?
Cholic acid and chenodeoxycholic acid
After __________resection, bile acids are not recirculated to the liver but are excreted in feces. The bile acid pool is thereby depleted, and fat absorption is impaired, resulting in steatorrhea
Ileal
T/F mucin-utilizing bacteria are important for the regular turnoverand replenishment of the mucin layer in the GI
TRUE
T/F MUC-2 is the major component of the mucin layer in the GI
TRUE
What are metabolic processes in which the Hypoxia Inducible Factor-1 is involved
- Cellular adaptations to hypoxia (pH regulation, glucose uptake, erythropoyesis, lipid metabolism)
- Beneficial effects for the intestinal barrier function (increases paracellular resistance by upregulating claudin-1, JAM and occludin) which reduces bacterial translocation and associated inflammation
- HIF-1 also increases production of mucins
- HIF-1 supresses inflammation
Only monosaccharides are absorbed. Monosacarides cannot diffuse through pores in the cell membrane, they enter the cell by combining with protein carriers via __________ (fructose)or by a ______________(glucose, galactose)
Facilitated diffusion
Na-dependent cotransport
What are the two organs that do not require insulin to uptake glucose
Liver and brain
Glucose __________ is the process how glucose is captured in the cell. This process is irreversible in most tissues except _____________ where the enzyme ____________ is available for reversing the reaction.
Phosphorilation
liver, renal tubular epithelium, intestinal epithelial cells
Glucose phosphatase
When the body has a high energy demand, epinephrine and glucagon stimulate the formation of cAMP in the cell, which initiates a cascade of chemical reactions that activate _____________ , which re-forms glucose from glycogen
Phosphorilase
a total of ___ moles of ATP are formed for each mole of glucose used by the cells
38 (2 from glycolysis, 2 from citric acid cycle, 34 from oxidative phosphorilation in mitocondria)
During anaerobic conditions, the end products of the glycolytic reaction ________ and __________ combine under the influence of the enzyme __________ to form ___ and ___________
Pyruvate and NADH
lactic dehydrogenase
lactateand NAD+
T/F The pentose phosphatase pathway is an alternative mechanism of glucose utilization (independent of glycolysis) in the event of enzymatic abnormalities in the glycolysis pathway
TRUE
The process of carbohydrate formation from proteins and fats is called
Gluconeogenesis
All fats in the diet are absorbed into the lymph in the form of
Chylomicrons
Chylomicrons are removed from the plasma as they pass through the capillaries of _______and ________tissue. These tissues have large quantities of the enzyme___________ which hydrolyzed triglicerides of chylomicrons into _________and _________
addipose tissue and liver tissue
lipoprotein lipase
fatty acids and glycerol
T/F free fatty acids are fatty acids bound with proteins such as albumin
TRUE
List at least 10 causes of extrahepatic bile duct obstruction in dogs and cats
Describe/draw a hepatic lobule, portal lobule and portal acinus
List toxins implicated in hepatic encephalopathy
ALF - icterus
ALF - primary coagulopathy
ALF - primary coagulopathy II
ALF - secondary coagulopathy
ALF - secondary coagulopathy II
ALF - clinical sx - hypoglycemia and sepsis
ALF - HE
ALF - ammonia
ALF - ammonia II
ALF - clinical signs of HE
ALF - HE neuroinflammatory response
ALF - toxins implicated in HE
ALF - precipitating factors for HE
ALF - diagnosis
ALF - diagnosis - transaminases
ALF - diagnosis - inducible enzymes
ALF - diagnosis - electrolyte imbalances
ALF - diagnosis - ammonia
ALF - diagnosis - imaging
ALF - diagnosis - FNA/biopsies and coats
ALF - diagnosis - TEG
ALF - main treatments
ALF - treatments - fluids
ALF - treatment - fluids II
ALF - fluids maintenance
ALF - nutrition
ALF - nutrition - vitamins
ALF - supplements
ALF - nutrition - supplements II
ALF - nutrition - NAC
ALF - specific therapies / antidotes
ALF - Other therapies -> naloxone
ALF - management of complications
ALF - management of complications II
ALF - future therapies?
ALF - future therapies II
ALF - prognosis
Comparison of key features between vomiting and regurgitation
DDX for regurgitation
Physiology of vomiting
o The vomiting reflex is mediated by the vomiting center in the medulla.
o Vagal and sympathetic afferent pathways from the GI tract transmit impulses to the vomiting center when stimulated by inflammation or overdistention.
o The vomiting center also receives stimulation from within the brain: the vestibular system, cerebrum, and chemoreceptor trigger zone provide input to the vomiting center.
o The latter is a specialized region (area postrema) that is located on the floor of the fourth ventricle and lacks an intact blood-brain barrier.
o The chemoreceptor trigger zone is sensitive to several common drugs and toxins.
o Sufficient stimulation of the vomiting center results in the initiation of vomiting.
o A period of intestinal antiperistalsis is followed by a highly coordinated sequence of events, beginning with a deep inspiration and ending with a strong simultaneous contraction of the diaphragm and abdominal wall musculature and relaxation of the lower esophageal sphincter.
DDX for vomiting
