Translational Physiology Block 6 Flashcards
Describe achalasia
lack of relaxation of the LES secondary to loss of myenteric plexus; symptoms: dysphagia, regurgitation, aspiration, chest pain; necessity for surgery?
Describe Hirschsprung disease
absence of ganglion cells of Meissner and Auerbach plexus in distal colon (congenital polygenic disorder); markedly distended colon, constipation, vomiting, and abdominal distension; treated with surgery
Why are GI patients vulnerable to pneumonia?
Raising gastric pH, using proton pump inhibitors to prevent ulcers, lowers the barrier to gram-negative bacterial colonization of the stomach; If patient develops esophageal reflux (common in these patients), pneumonia can result
Describe Zollinger-Ellison syndrome (gastrinoma)
diagnosis: clinical: GERD, peptic ulcer, diarrhea; hyperchlorhydria; hypergastrinemia; secretin stimulation test; caused by deletions/mutations in the MEN-1 gene;
SRS should be the initial test for localizing tumors; Somatostatin receptor scintigraphy involves using a labeled somatostatin analog to bind to overexpressed receptors on the surface of a gastrinoma
Why does helicobacter pylori produce peptic ulcers?
heliobacter pylori (gram-negative) colonizes antral mucosa; H. pylori-induced antral inflammation inhibits the release of somatostatin by antral D cells; Treatment: inhibition of acid secretion heals damaged epithelial cell lining and antibiotic therapy eradicates the bacteria
Describe vomiting.
Abolition of intestinal slow-wave activity that is linked to propulsive peristaltic contractions; retrograde contractions, beginning in the ileum and progressing to the stomach (accompanied by contraction of abdominal and inspiratory muscles against a closed glottis); movement of the larynx upward and forward and relaxation of the upper esophageal sphincter (it seems that all sphincters above the colon must be relaxed in this behavior) are required for oral propulsion
Describe cystic fibrosis.
autosomal recessive disease; defective chloride channel: secretion of very thick mucous and high sodium chloride levels in sweat; destruction of pancreas and replacement with fibrotic tissue results in increased fat in stool
Describe Sjogren syndrome.
autoimmune diseases that affects salivary secretion; xerostomia (dry mouth) and keratoconjunctivitis (dry eyes) and parotid gland enlargement; treatment: immunosuppresants, eye drops, and oral fluid ingestion
Describe oral dehydration solution.
Contains varying concentration of glucose, sodium, chloride, and bicarbonate and is extremely effective in enhancing fluid and electrolyte absorption in secretary diarrhea when the intestine secretes massive amounts of fluid (reverse dehydration and metabolic acidosis)
Describe congenital chloridorrhea.
Congenital absence of apical chloride/bicarbonate exchange (exchange in erythrocytes and kidney is unaffected); diarrhea with extremely high stool chloride concentration; alkalotic (increased plasma bicarbonate)
Describe secretory diarrhea.
caused by bacterial exotoxins that induce fluid and electrolyte secretion by the intestine (enterotoxin; E. coli and cholera); increase in the number of bowel movements or decrease in stool consistency; treated with ORS
What else can cause diarrhea? what is osmotic diarrhea?
Verner-Morrision syndrome- tumor producing VIP; glucagonomas; carcinoid syndrome- serotonin-secreting tumor
dietary nutrient that is not absorbed (primary lactase deficiency)
Describe primary lactase deficiency.
Normally lactase activity decreases after weaning; hydrogen gas in the breath is increased (nonabsorbed lactose is metabolized by colonic bacteria to hydrogen gas, which is absorbed into the blood and excreted by the lungs during expiration)
Describe glucose-galactose malabsorption.
Diarrhea resulting from reduced small intestine sodium and fluid absoprtion (and fluid secretion secondary to the osmotic effects of nonabsorbed monosaccharide); SGLT1 defective or absent (patients do not have glycosuria due to SGLT2 in renal tubules)
Describe Hartnup disease and cystinuria.
Malabsorption of neutral amino acids (particularly phenylalanine) = Hartnup (compensation by oligopeptide transfer; cystinuria = cationic amino acids); Hartnup is characterized by cerebellar ataxia and cystinuria by kidney stones
Describe lysinuric protein intolerance.
Autosomal recessive disorder of amino acid transport across the basolateral membrane (also affects kidney); not compensatory mechanism
Describe pernicious anemia.
Antibody-mediated immunity against parietal cells; impaired cobalamin absorption; increased plasma gastrin levels; megaloblastic anemia (enlarged RBCs); manifests as peripheral neuropathy but can result in ataxia and weakness
Describe hemochromatosis.
Body absorbs excessive iron from diet (relative to body iron stores; normally there is negative feedback); excess iron stored in liver leads to cirrhosis (may also cause pancreatic damage from diabetes mellitus, pituitary and gonadal failure, arthritis, and cardiomyopathy); women are protected by menstrual bleeds; treatment is phlebotomy (monitoring of ferritin levels)
Describe anemia of inflammation.
Cytokine interleukin-6 stimulates hepcidin expression (downregulates DMT1 expression and ferroportin activity); reduced duodenal iron absorption
Describe jaundice.
yellowing of the skin and whites of the eyes; is a result of elevated bilirubin (extracellular fluid)
What can cause jaundice?
Increased destruction of red blood cells or hemolysis may occur with rapid release of free, unconjugated bilirubin into the circulation. Unconjugated hyperbilirubinemia occurs commonly in neonates not only because of increased production of heme but also because of the immaturity of the pathways for glucuronidation in the liver. Obstruction of the bile ducts or damage to the liver may also result in jaundice.
How do urine and stool samples appear in patients with obstructive jaundice?
tests for urobilinogen in urine are negative; clay colored stool
Describe acute pancreatitis.
diffuse necrosis of the pancreas by release of activated enzymes; associated with alcoholism and biliary tract disease (gallstones); may be caused by hypertriglyceridemia (disorder of lipid metabolism) or scorpion stings (cholinesterase inhibitors) symptoms include intense abdominal pain (radiating to the back) accompanied by nausea, vomiting, and fever (may lead to shock); elevated amylase and lipase levels in circulation; treated with serine protease inhibitors and gabexate
Describe cholestasis.
impaired excretion of conjugated bilirubin; altered plasma membrane composition and fluidity; inhibition of membrane proteins (sodium/potassium pump); reduced expression of genes encoding transporters for bile acids and other organic anions; increased permeability of the paracellular pathway (backdiffusion of biliary solutes into the plasma); altered function of microfilaments (decreases contractions of bile canaliculi); loss of the polarized distribution of some plasma membrane proteins
Describe gallstones.
When there are two few bile acids to form mixed micelles, cholesterol-enriched vesicles aggregate to form large multilamellar vesicles (cholesterol crystals nucleate); may be promoted by gallbladder mucin
Is it true that cholesterol and phospholipids are secreted together into the bile ducts?
Yes; form unilamellar bilayered vesicles
What controls cholesterol synthesis?
In the short term, decreased intracellular levels of ATP lead to phosphorylation of HMG-CoA reductase, which reduces its activity
SRE (sterol regulatory elements)-binding proteins are membrane-bound basic helix-loop-helix transcriptional activators that control genes involved in the synthesis and receptor-mediated uptake of cholesterol and fatty acids
Describe Wilson’s disease.
inadequate excretion of copper (autosomal recessive); Mutation of ATP7B, the pump responsible for copper accumulation in the trans-Golgi network; clinical: ataxia, tremors, increased salivation, and behavioral changes; low serum ceruloplasmin; Kayser-Fleischer rings; increased urinary copper excretion
How is Wilson’s disease treated?
chelating excess copper with penicillamine
