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

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