Case 4: Peptic Ulcer Disease

AA from lumen into intestinal epithelial cell
mostly Na dependent transport
Driven by low intracellular Na concentrations (maintained by Na/K ATPase on basolateral)
AA from intestinal epithelial cell to interstitial fluid
facilitated transporters (Bidirectional)
Renal epithelium AA transport
Na depdendent transport proteins (reabsorption of aa in glomerular filtrate)
Hyperaminoaciduria in ___ disease
Hartnup
AA pool
diet and degradation of existing proteins
Lysosomal Protein turnover
Ubiquitin-Proteosome pathway
targets intracellular proteins for degradation
19S
___
Lysosomal protein turnover during starvation
Activation AMPK (favors proteolysis)
Activates TSCI/TSC2 –> INACTIVATES Rheb and mTOR
FAVORS AUTOPHAGY
Lysosomal protein turnover during high energy state
(insulin)
Activation of AKT (favors protein synthesis)
Inactivates TSC1/TSC2
Activates Rheb and mTOR
INHIBITS AUTOPHAGHY
Cystinuria
unable to absorb cystine and 3 nonessential aa from intestine and glomerulous ….
Erythropoietin
hormone
regulation of RBC production
What conditions cause increased rate of RBC production?
Formation of hemoglobin
1.
2.
3.
4.
Condition in which the number of RBCs in circ increased by hypoxia or genetic aberration is?
polycthemia
Iron deficiency anemia can result from
1. Dietary lack (infants, poor, elderly, teenagers)
2. Impaired absorption (sprue, chronic dia)
3. Increased requirement (child, premeno woman)
4. Chronic blood loss
Dx of Iron deficiency
Decreased Hct, Hb, serum iron and ferritin
Blood smear: microcytic + hypochromic, poikilocytosis (abnormal shape)
Increased TIBC
Iron deficiency in adult male or post-menopausal woman, must first rule out?
Gastrointestional bleeding
Drugs that decrease acid
H2 receptor antagonists “dine”
Proton pump inhibitors “prazole”
H2 receptor antagnoists
“dine”
competively inhibit
Cimetidine (inhibits Cyto P450)
Proton pump inhibitors
“prazole”
Omeprazole
May decrease efficacy antiplatelets (clopidogrel)
Drugs that neutralize acid
Antacids “- hydroxide”
Antacids
AlOH (constipation)
MgOh (diarrhea)
use together
Drugs that promote mucosal defense
Sucralfate (doesn’t alter pH)
Collodial bismuth
Prostaglandins (Rx: NSAID included ulcers)
sucralfate
viscous gel
Misoprostol
prostaglandin analogue
Eicosanoid
three classes
Prostglandins, thromboxanes, leukotrienes
20C
inflamm response, smooth m contraction, BP reg, broncoC/D
pathway of arachodonic acid, start with diet
Linoleate –> Arachodonic acid –> 1. Epoxides 2. Leukotriene 3. thromboxane 4.
Arachidonic acid to prostaglandins
AA –> PGG2 –> PGH2 –> 1. Thrombaxane (hex ring) 2. Prostaglandin (pent ring)
PG nomenclature
PG: prostaglandin
A/D/E/F/G/H: family, refers to substituents
1/2/3: how many double bones in substituents
*Series 2 naturally forms in body
Cyclo-oxygenase
initial biosynthesic step
forms five-membered ring
add four atoms of oxygen to ___
Action of aspirin
acetylates group to COX enzyme IRREVERSIBILY inactivating it
NSAIDS besides aspirin action
Reversible
block both COX1 and COX2
Celebrx and ____
Prominent eicosanoids formed in platelets?
TXA2 (thromboxane)
Eicosanoids related to asthma
Prostaglandings and leukotrienes
PGD2
LTB4, LTC4, LTD4
Eicosanoids related to inflammatory bowel disease
Eicosanoids related to rheumatoid arthritis
Eicosanoids related to glomerulonephritis
Eicosanoids related to cancer
Eicosanoids related to cardiovascular disease
Cyclo-oxygenase inhibitors
NSAIDs (all but aspirin are reversible) affect COX1+2
serious adverse effects of aspirin
hepatic encephalopathy
aspirin induced airway activity
Thromboxane antagonists mechanism
block TXA2 creation or receptors
Leukotrine inhibition mechanism
inhibition 5-oxygenase, which inhibits the lipoxygenase pathway
5-LO
Linoleic acid is an omega-__?
6
PGI2
vasoD, inhibit platelet agg
TXA2
vasoC, platelet ACTIVATION
PGH2 converts to
PG D/E/F/I 2
TXA2
PGD2
PG
Alpha-Lenolenic acid –>
EPA
Resolvins and protectins, d-series maresins
A-lenolenic–>
DHA
COX inhibitors
NSAIDs
Glucocorticoids
NSAIDs prevent conversion of ___ to ___?
prevent arachidonic acid to subsequent prostaglandins and thromboxanes
Leukotrienes
Zileuton
inhibits 5-lipoxygenase
Zafirlukast and Montelukast
antagonize cysteinyl leukotriend receptor receptor
*instead of zileuton