Clinical Flashcards
Zollinger-Ellison Syndrome
gastrinomas = tumors producing excessive amounts of gastrin…stimulant for gastric parietal cells to secrete HCL
tumors outside the stomach –> do not have negative feedback loop so will stimulate overwhelming amounts of acid –> chronic ulcers that are too much for defense systems
Barrett’s esophagus
injured squamous epithelium is replaced with ‘specialized columnar’ epithelium
more acidic resistant…but risk of becoming an esophageal adenocarcinoma
gastroesophageal reflux
recurrent heart burn symptoms
indicates the esophageal epithelium is being exposed to and damaged by refluxed gastric acid
major mechanism = abnormal in neuromuscular function of the LES….particularly frequent transient LES relaxation
long term complications of gastroesophageal reflux –> dysphagia
- development of stricture
- damage to neuromuscular apparatus –> impaired esophageal peristalsis
- esophageal adenocarcinoma (BE)
Hirschsprung’s disease
constipation
defecation reflex is missing
reasons that this could happen
1. anti-Ach medication –> inhibits intestinal neurally mediated perstaltic movements
- narcotic meds –> inhibits contraction of intestinal SmM directly
- sedentary lifestyle –> inhibits extrinsic stimulation of intestinal muscle contraction
- low fiber diet –> limits formation of fecal residue buld which limits rectal distention
- conscious inhibition of relaxation of external anal sphincter
xerostomia
dry mouth
occurs largely by a reduction in salivary secretion in the mouth…or by drying out of these secretions faster than they can be produced
conditions that can cause dry mouth
- sjogren’s syndrome
- mouth breathing/dehumidified air
- medications - anti-Ach (bentyl) or tricyclic antidepressants (elavil)
consequences of xerostomia
- poor oral cleansing of food particles –> bacterial proliferation (halitosis, caries, gingivitis)
- poor lubrication - difficult mastication adn swalloing (dysphagia)
- poor acid buffering
mout = caries, gingivitis
esophagus = heartburn, esophagitis
Sjorgren’s syndrome
loos of salivary gland function and lacrimal gland function
achlorhydria –> pernicious anemia
vitamin B12 deficiency or malabsorption in terminal ileum
could be defective intrinsic factor
cimetidine and ranitidine
H2 receptor blockers
parietal cells = target
‘acid-suppressant drug’
side effects: diarrhea, headache, drowsiness, fatigue, constipation, hallucinations, gynecomastia (men), galactorrhea (women)
gastritis
inflammation of gastric mucosa
mild to moderate chronic gastritis is very common in the general population, especially in the middle to later years
can be superficial or deep and cause atrophy to mucosa
95% caused by chronic infection by Helicobacter pylori
Helicobacter Pylori (H. Pylori)
corkscrew in shape…so can easily penetrate the stomach’s protective lining , breaks down mucosal barrier and stimulates gastric secretion
can survive gastric acid due to urease enzyme
adheres to the epithelial cells stimulating adhesins, ammonia, proteases, and immune response
(+) gastrin by G cells via systemic circulation
(+) HCl by parietal
peptic ulcers
associated with chronic H. Pylori infections –> underlying epithelium exposed
and acid secretion brought by bacteria –> digest the gastroduodenal wall –> peptic ulcer
***during peptic ulcers due to H Pylori infection…although the acid secretion is increased - its augmentation occurs at a moderate rate
factors that predispose you to peptic ulcers besides bacteria
- smoking –> increased nervous stimulation of the stomach secretory glands
- alcohol –> tends to breakdown the mucosal barrier
- aspirin and NSAIDs –> breakdown mucosa
urease mechanism
urea + H20 –> NH3 + CO2
NH3 neutralizes the gastric acid
zollinger-ellison syndrome
abnormally high gastrin acid secretion rate = hallmark symptom
–> what separates it from gastric ulcers
= duodenal ulcers or tumors like gastrinomas…which secrete very high amounts of gastrin in an unregulated fashion
common gastrinoma location = pancreas
treatment = surgery to remove tumor if primary one can be found…otherwise proton pump inhibitors (PPIs) + H2 blockers
proton pump inhibitors (PPIs)
most popular agent to treat ulcer peptide disease
example = omeprazole –> binds the pump covalently on the extracytoplasmic surface
atropin, oxybutinin, diphenhrydamine
anticholinergic medications
decreases acid secretion
Cystic Fibrosis Transmembrane Regulator
the Cl- channel in the apical membrane of acinar cells in the exocrine pancreas
this is needed for HCO3- secretion…why see decrease in pancreatic function with cystic fibrosis
pancreatitis
most caused by gallstones that block the flow of pancreatic enzymes or by excessive amounts of alcohol
risk factors:
- alcohol abuse
- gallstones
- hyperlipidemia
- genetic (Cystic Fibrosis)
- hyperparathyroidism
2 main blood tests to diagnose pancreatitis
- serum amylase
- an increase = pancreatitis - serum lipase
- acute will have raised levels
lower total cholesterol, HDL, LDL = severe acute pancreatitis
Cystic Fibrosis and chronic pancreatitis
most common lethal genetic disease in whites
AR, chromosome 7
clinical signs = recurrent pulmonary infection, chronic pancreatitis, abnormal sweat, malabsorption, and fat in shit
oral enzyme replacement therapy
gallstone disease
2 types = cholesterol or bilirubin (pigment stones)
most = cholesterol
balance between normal ratios of cholesterol to the other biliary lipids is disrupted
risk factors
- obesity, contraceptives, estrogen, old age, sudden weight loss, genetics
cholecystitis
inflammation of gallbladder when flow of bile is stopped
cholestasis
more serious stoppage of bile from liver into duodenum
cholangitis
inflammation of the bile ducts outside the liver due to bacterial infection
biliary cirrhosis
inflammation and obstruction of the bile duct inside the liver….dead cells replaced with fibrous scar tissue
gall stone disease treatment
cholecystectomy
lactase deficiency (lactose intolerance)
lactose passes into colon since not digested in the small intestine
metabolized by colonic bacteria –> releases gas
sucrase-isomaltase deficiency
low digestion in the SI brush border –> lowers absorption, since cannot digest down to monosaccharides well
glucose-galactose malabsorption syndrome
rare genetic disorder
cannot absorb Glu or Gal
mutations in SGLT1
diarrhea
milder mutations are associated with irritable bowel syndrome
trypsinogen deficiency
pancreatic insufficiency leads to low levels of plasma proteins
Hartnup disease
hereditary
defective renal and intestinal transport of netural amino acids (B transporters)
not protein deficient since normal absorption of oligopeptides
but lack niacin (B3) which is made from tryptophan (a neutral amino acid…which is lose in the urin)
Cystinuria
defect in b0,+ transporters in renal and intestinal cells
accumulation of cysteine in urine and causes kidney stones
no protein deficiency because normal absorption of oligopeptides
atrophic gastritis
decreases secretion of intrinsic factor from parietal cells
–> B12 deficiency
pancreatic exocrine insufficiency –> vitamin B12 deficiency
can interfere with the digestion of the binding proteins in the SI so that IF can bind to it
ileal disease or resection –> B12 deficiencyt
can decrease the binding and absorption of B12
hemochromatosis
hereditary disorder in which the body absorbs excessive iron from the diet
treatment = phlebotomy
celiac sprue
primary malabsorptive disorder which affects the SI mucosa
disease is due to toxic effect of gluten (protein in wheat flour)
causes villous atrophy
unabsorbed nutrients cause osmotic diarrhea
FAs are converting by bacteria to hyroxy-FAs which are powerful seretagogues in the colonic mucosa
symptoms: weight loss, fatty shit, anemia, vitamin deficient,
treatment = gluten free diet
causes of steatorrhea
bile deficiency –> no absorption of cholesterol, cholE, and lipid soluble vitamins
*** still get TG digestion and absorption of FAs and 2MG is 50% normal
pancreatic insufficiency –> no pancreatic lipases and very little fat absorption occurs
Rickets
hypocalcemia, bone deformation (bow legs)
lack of vitamin D causes it –> no Ca2+ absorption
sunlight
bacterial exotoxin
peptide produces by bacteria
bacterial endotoxin
an exotoxin that induces changes in intestinal fluid and electrolyte movement
E. coli
produces two distinct enterotoxins (heat-labile and heat-stable, STa, toxins)
that induce fluid and electrolyte secretion via two distinct receptors and 2nd messengers systems
3 mechanisms that secretagogues act by
- activate adenylyl cyclase on basolateral side –> cAMP –> PKA
(VIP, heat labile toxin) - guanylin receptor on apical side –> cGMP –> PKG
(heat stable toxin, STa) - stimulate phospholipase C –> IP3 –> DAG –> PKC –> [Ca2+]i –> PKC –> CaM kinase
***all promote net secretion by phosphorylating apical membrane transporters and other proteins
salilvary gland fluidnature
alkaline
stomach fluid nature
highly acidic
biliary tree fluid nature
alkaline
pancreatic fluid nature
highly alkaline
jejunum and ileum fluid nature
alkaline
colon fluid nature
acidic
fecal excreta =
100mL water and 25-50 gram of solids
5 potential causes of diarrhea
- deficiencies in normal transport systems
- congential chloride diarrhea
- glucose or galactose malabsorption
- sucrase-isomaltase deficiency - malabsorption of a nonelectrolyte (osmotic diarrhea)
- intestinal hypermotility (lower absorption)
- enhanced rate of net secretion due to luminal secretagogues
- reduction of mucosal surface area (celiac, IDB)
secretory diarrhea
endogenous secretions of fluid and electrolytes from the intestine
leading causes (E. coli or traveler’s diarrhea) and vibrio
enterotoxins raises levels of cAMP, gGMP and Ca2+ –> increase secretions
***nutrient coupled Na+ absorption is not affected
oral rehydration solution containing Na, K, Cl, HCO3 and glucose is effective
metabolic acidosis….loss of Na, K, Cl, and HCO3
excessive vomitting
metabolic alkalosis
loss of fluid, H, and Cl
congentical chloridorrhea
metabolic alkalosis
loss of Cl- and Na+ and retention of HCO3-
normal stool lab values
Na = 20-30
K = 55-75
Cl = 15-25
HCO3 = 0
secretory diarrhea lab values
Na = 40-140 (high)
K = 15-40 (low)
Cl = 25-105 (normal-high)
HCO3 = 20-75 (high)
congentical chloridiarrhea
Na = 30-80 (high)
K = 15-60 (low - normal)
Cl = 120-150 (very high)
HCO3 <5 (barely high)
patient with Crohns disease….has the following, and what are the causes of each
- cachexia
- volume depletion
- steatorrhea
- inadequate uptake of calories and malabsorption of vitamins and minerals
- decreased intestinal transit time, increased osmolarity of the luminal content, decreased water and electrolyte absorption, decreased absorption of bile salts stimulates water secretion from the colon
- impaired micelle formation and decreased fat absorption
