Translational Physiology Block 6 Flashcards Preview

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Flashcards in Translational Physiology Block 6 Deck (73):
1

Describe achalasia

lack of relaxation of the LES secondary to loss of myenteric plexus; symptoms: dysphagia, regurgitation, aspiration, chest pain; necessity for surgery?

2

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

3

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

4

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

5

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

6

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

7

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

8

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

9

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)

10

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)

11

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

12

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)

13

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)

14

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)

15

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

16

Describe lysinuric protein intolerance.

Autosomal recessive disorder of amino acid transport across the basolateral membrane (also affects kidney); not compensatory mechanism

17

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

18

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)

19

Describe anemia of inflammation.

Cytokine interleukin-6 stimulates hepcidin expression (downregulates DMT1 expression and ferroportin activity); reduced duodenal iron absorption

20

Describe jaundice.

yellowing of the skin and whites of the eyes; is a result of elevated bilirubin (extracellular fluid)

21

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.

22

How do urine and stool samples appear in patients with obstructive jaundice?

tests for urobilinogen in urine are negative; clay colored stool

23

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

24

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

25

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

26

Is it true that cholesterol and phospholipids are secreted together into the bile ducts?

Yes; form unilamellar bilayered vesicles

27

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

28

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

29

How is Wilson's disease treated?

chelating excess copper with penicillamine

30

Describe the etiology of peptic ulcer disease.

helicobacter pylori, nonsteroidal anti-inflammatory drugs, and hypersecretory state

Imbalance between acid secretion and defense system preventing damage to epithelial cells determines the causation of ulcers

31

Describe in detail the role of H. pylori in the pathogenesis of peptic ulcer and gastric cancer

H. pylori attach to epithelial cells, blocks somatostatin and may cause inflammation (a precursor for malignancy)

32

Compare duodenal ulcers and gastric cancer.

duodenal ulcers: found in the antrum of the stomach; hypergastremia; increased acid secretion (hyperchlorhydria); infections occur when patients are in their teens; environmental factors: smoking

gastric cancer: located in the corpus; hypergastremia; achlorhydria; IL-gene SNPs; acquired at young age; environmental factors: smoking, high salt diet, and low fruit diet

33

What are possible treatments for peptic ulcers?

omeprazole (PPI); cimetidine; H2R antagonists; COX2 inhibitors; suppression of acid secretion; eradication of H. pylori

34

Describe duodenal ulcers.

patients with duodenal ulcer have serum gastrin levels that are near normal (slightly elevated). Their basal gastric acid secretion rates are modestly elevated, but they increase markedly in response to pentagastrin.

35

What are tests for diagnosing H. pylori?

CLOtest, Giemsa stain, and serology

36

A patient presents to the hospital with basal gastrin levels approximately 3 times higher than those found in a healthy individual. Basal acid production is also highly elevated. Administration of pentagastrin has little effect on acid production. Which of the following is the most likely diagnosis?

Gastrinoma; Zollinger-Ellison syndrome

37

In patients with gastrinoma, what are the expected results of a secretin stimulation test?

increased gastrin levels (inhibition of D cells; normal individuals show a decrease in gastrin levels)

38

What molecule is not inhibited by somatostatin?

acetylcholine

39

Describe the clinical features of cystic fibrosis (CF).

exocrine pancreas insufficiency, chronic lung disease, excessive loss of electrolytes in sweat, and malnutrition

40

Describe pancreatic insufficiency as a feature of cystic fibrosis. What are complications associated with pancreatic insufficiency?

Epithelial cells do not secrete chloride and therefore water -> abnormal intestinal mucous (solute backup results early activation of zymogens leading to destruction of cells and replacement with fat and fibrosis)

meconium ileus at birth (stool is stuck); distal intestinal obstruction syndrome later in life (DIOS) results in thick mucous (poorly hydrated) stool; abnormal motility results in constipation and loss of appetite

poorly controlled fat absorption (steatorrhea, dehydration, and malabsoption of lipid-soluble vitamins)

insulin deficiency following scarring of the pancreatic islets (fibrosis)

autodigestion

41

Which cells of the pancreas are directly destroyed in CF?

acinar, ductal, and islet

42

Can pancreatic enzymes be found in the circulation of patients with cystic fibrosis?

Yes; can be measured with immunoreactive trypsinogen

43

What is an assessment tool for diagnosing pancreatic insufficiency?

stool elastase (which is not digested by the GI tract); its concentration in feces reflects exocrine pancreatic function

44

Describe the various nutritional consequences of pancreatic insufficiency in cystic fibrosis

Patients need a well-balanced, high calorie diet supplemented with fat-soluble vitamins and minerals
(high in fat and protein)

pulmonary disease and chronic infection results in a energy imbalance

lower BMI is associated with a lower FEV1

Liver and gallbladder dysfunction may lead to reduction of amounts or precipitation of bile acids

Overgrowth of intestinal bacteria

GERD; hypoproteinemia

patients with some pancreatic function may develop pancreatitis

45

Describe treatment of pancreatic insufficiency and malnutrition in cystic fibrosis

Pancreatic enzyme replacement therapy contains lipase, protease and amylase (coated to protect them from the acidic environment of the stomach; some have addition of bicarbonate)

proton pump inhibitors and administration of histamine receptor 2 antagonists; some patients require a feeding tube

supplementation of salt, calcium, zinc, and iron

low vitamin K presents as petichiae

46

What are symptoms of poor prognosis in patients with cystic fibrosis?

poor weight gain, foul smelling, large volume stools

47

A 9 year old girl with CF, who is also a gymnast, complains that she is having difficulty staying on the balance beam. The most likely cause is a deficiency of which of the following vitamins?

Vitamin E

48

What is the etiology of obesity? Describe the shift in the United States' nutrition patterns.

Biological factors (fat cell number and resting energy expenditure): FTO gene

Behavioral factors include dietary intake, physical activity, medication (specifically beta blockers)

increased portion sizes and high fat/caloric diet

49

What are different therapies for obesity? Are they effective?

bypass surgery (yes; may decrease incretins); behavioral modification (maybe; must be sustained which is very difficult to accomplish; low glycemic index); appetite suppressors (rather ineffective due to nausea); cannibinoid receptor blocker showed efficacy with major adverse effects;

50

What would be the expected effects following the attenuation of GIP signaling?

Insulin release would be diminished by about 70%, while serum glucose would be unchanged (slight decrease)

Decreased glucose absorption in the small intestine

51

What is an incretin? Name them.

Conceptual hormone mediating the enteroinsular axis; released from small intestine by glucose-containing meals and stimulates the release of insulin from pancreatic beta islet cells.

Glucagon-like peptide and GIP

52

Define the relationship of GIP and insulin through evolution.

During evolution, as organisms became more complex and developed an alimentary (GI) tract, insulin moved to a “safer location” outside the GI tract, protecting it
from the animal’s only physical connection to the outside world. However, a messenger connecting the GI tract to the pancreas was needed. Thus, the development of
incretins

53

How do incretins contribute to the development of obesity?

overnutritions increases incretin concentrations resulting in: accumulation of fat, obesity, hyperinsulinemia, and insulin resistance.

54

What is the signal for release of GIP?

lipids and carbohydrates (seems primarily carbohydrates)

55

How are beta cells and K cells similar?

Both are endocrine cells (express, process, store and release hormones upon stimulation); both can cause translocation of GLUT4 for the plasma membrane through PI3K and decrease glycogen synthase through GSKb

56

Describe three complications of portal hypertension

manifests as portal hypertensive bleeding (variceal), accumulation of ascites, or encephalopathy

57

How does cirrhosis cause portal hypertension?

In liver cirrhosis the fibrosis leads to decreased vascular radius and decreased vascular compliance which significantly contribute to increased portal pressure (intestine becomes hypoxic stimulating release of VEGF and endothelial nitric oxide synthase)

58

What is the effect of portal hypertension on splanchnic circulation?

a vicious cycle of vasodilation, decreased effective plasma volume, sodium/water retention, increased intravascular volume and flow

59

Describe shunting of blood in response to portal hypertension. Where else can the blood go?

If portal pressure rises above 12mmHg, flow reverses into the coronary vein and results in the dilatation of esophageal varices.

fluid accumulation in peritoneal space (ascites)

60

What happens to the kidney as a result of decreased effective plasma volume?

initially prerenal azotemia: enhanced proximal tubular reabsorption of salt and water, as well as urea (BUN), calcium, uric acid, and bicarbonate

followed by oliguria

61

Does portal hypertension affect respiratory system?

Yes; shortness of breath and hypoxemia (worse will standing); V/Q mismatch (overperfusion)

some patients present with pulmonary hypertension

62

How is ascites managed?

diuretics, salt restriction, weight loss, and paracentesis (drainage); albumin infusion??

63

Describe role of TIPS in management of refractory ascites

Transjugular Intrahepatic Portosystemic Shunt: reduces GI bleeds; reduces chance of infection, improves renal function, and improves protein metabolism (contraindications are liver dysfunction, cardiovascular disease and pulmonary hypertension; also increases the risk of encephalopathy)

64

How is hepatic encephalopathy treated?

antibiotics and lactulose (reduce ammonia production and absorption)

65

Describe preventive and treatment strategies for management of variceal bleeding

band ligation; important to screen for presence of varices; noncardio-selective beta blockers

66

Gastric bypass surgery causes what changes to secretion of peptides and serum glucose?

no change to glucose, IGF, growth hormone, and ghrelin; decreased GIP

67

What is the action of the drug Rimonabant? exenatide?

cannibinoid receptor antagonist; GLP-1 receptor agonist (reduced caloric intake)

68

What is the mechanism in which NSAIDs can cause peptic ulcer disease?

Increasing vasoconstriction in mucosal lining

69

What is the mechanism of antacids?

decrease cellular cAMP levels (mimic prostaglandins and somatostatin)

70

Why is the urea test (isotope-labeled) useful in diagnosing peptic ulcers?

H. pylori have urease (neutralize acid) function which cleaves urea, which can be measured by isotope-labeled expiratory carbon dioxide

71

Dark, tarry stools (melena) is indicative of a bleed in the GI tract. Which is the most likely cause of the melena?

Upper GI tract bleed (bacterial processing); increased motility in the upper GI tract can cause hematochezia (bright red stool), which can be confused with lower GI tract bleeds

72

Compare the symptoms of duodenal and gastric ulcers/

duodenal: pain 1-3 hours after a meal or during the night
gastric: pain precipitated by food (loss of appetite and weight loss)

73

What is the mechanism for why peptic ulcers manifest as steatorrhea?

inactivation of pancreatic enzymes; bile salts not working; decreased surface area for fat absorption (pancreatic enzymes are inactive at low pH and bile acids are protonated at low pH losing their ability to form micelles)