Absite ReviewAbsite ReviewRTC 1/22/10RTC 1/22/10

TopicsTopics

Cover Highlights of the following:Cover Highlights of the following:

••

Gastrointestinal HormonesGastrointestinal Hormones

••

Transplant Transplant (rejection, medications(rejection, medications))

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HematologyHematology

Gi HormonesGi Hormones

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GastrinGastrin

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Origin: G cells in antrumOrigin: G cells in antrum

••

Target: parietal and chief cellsTarget: parietal and chief cells

••

Action: Action: HCl, intrinsic factor, pepsinogen secretion HCl, intrinsic factor, pepsinogen secretion

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Stimulators: AAStimulators: AA’’s, vagal input, antral distension, pH>3s, vagal input, antral distension, pH>3

••

Inhibitors: secretin/CCK, somatostatin, pH<3, VIP, GIPInhibitors: secretin/CCK, somatostatin, pH<3, VIP, GIP

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Omeprazole blocks H/K ATPase of parietal cellOmeprazole blocks H/K ATPase of parietal cell

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Acetylcholine Acetylcholine and and Histamine Histamine cause HCl secretioncause HCl secretion

GI hormonesGI hormones

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Somatostatin Somatostatin ““the great inhibitorthe great inhibitor””

••

Origin: D cell in antrumOrigin: D cell in antrum

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Target: many cells in GI tractTarget: many cells in GI tract

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Action: inhibits release of gastrin and HCl, insulin, glucagon, Action: inhibits release of gastrin and HCl, insulin, glucagon, secretin; secretin; decreases biliary and pancreatic output. decreases biliary and pancreatic output.

••

Stimulator: acid in duodenumStimulator: acid in duodenum

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Octreotide Octreotide (somatostatin analogue)(somatostatin analogue)

GI hormonesGI hormones

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CholecystokininCholecystokinin

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Origin: I cells of duodenum and jejunumOrigin: I cells of duodenum and jejunum

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Action: Action: gallbladder contraction, sphincter of Oddi relaxation, gallbladder contraction, sphincter of Oddi relaxation,

pancreatic enzyme secretion and intestinal motility.pancreatic enzyme secretion and intestinal motility.

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Stimulators: amino acids and fatty acidsStimulators: amino acids and fatty acids

GiGi

hormoneshormones

••

SecretinSecretin

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Origin: S cells of duodenumOrigin: S cells of duodenum

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Action: Action: pancreatic HCO3 release, bile flow; inhibits gastrin pancreatic HCO3 release, bile flow; inhibits gastrin and HCl releaseand HCl release

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Stimulators: fatty acids, bile, pH<4.0Stimulators: fatty acids, bile, pH<4.0

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Inhibitors: pH>4.0 and gastrinInhibitors: pH>4.0 and gastrin

QuestionsQuestions••

Which of the following statements are true or false?Which of the following statements are true or false?

••

Reducing vagal input will result in higher gastric Reducing vagal input will result in higher gastric pH and reduced HCl. pH and reduced HCl.

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TRUETRUE••

Rising pH levels in the duodenum stimulate secretion of somatostRising pH levels in the duodenum stimulate secretion of somatostatin.atin.••

FALSE FALSE ••

Amino acids cause increased release of cholecystokinin Amino acids cause increased release of cholecystokinin and secretin.and secretin.

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TRUETRUE••

Secretin stimulates biliary and pancreatic Secretin stimulates biliary and pancreatic flow, and flow, and increases gastrin release increases gastrin release from the antrum.from the antrum.

••

FALSEFALSE

GiGi

hormoneshormones

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InsulinInsulin••

Origin: beta cells in pancreasOrigin: beta cells in pancreas

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Action: cellular glucose uptake; Action: cellular glucose uptake; protein synthesisprotein synthesis

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Stimulators: glucose, glucagons, CCKStimulators: glucose, glucagons, CCK

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Inhibitors: somatostatin, Inhibitors: somatostatin, pancreatostatinpancreatostatin

GiGi

hormoneshormones

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GlucagonGlucagon

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Origin: alpha cells of pancreasOrigin: alpha cells of pancreas

••

Action: glycogenolysis, gluconeogenesis, lipolysis, ketogenesis,Action: glycogenolysis, gluconeogenesis, lipolysis, ketogenesis,

gastric acid and pancreatic secretion, gastric acid and pancreatic secretion, GI motility and GI motility and MMCMMC’’ss

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Stimulators: Stimulators: glucose, glucose, amino acids, acetylcholine, and amino acids, acetylcholine, and gastringastrin--releasing peptidereleasing peptide

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Inhibitors: Inhibitors: glucose and insulin; somatostatinglucose and insulin; somatostatin

••

Treatment for beta blockade overdoseTreatment for beta blockade overdose

GiGi

hormoneshormones

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Gastric Inhibitory PeptideGastric Inhibitory Peptide

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Origin: K cells in duodenumOrigin: K cells in duodenum

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Target: parietal cells in stomach Target: parietal cells in stomach

and and beta cellsbeta cells

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Action: Action: HCl secretion and pepsin; HCl secretion and pepsin;

insulin releaseinsulin release

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Stimulators: amino acids, glucose, Stimulators: amino acids, glucose,

longlong--chain FAchain FA’’s, and s, and pHpH

GiGi

hormoneshormones

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Vasoactive Intestinal Peptide (VIP)Vasoactive Intestinal Peptide (VIP)

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Origin: various cells in GI tract and pancreasOrigin: various cells in GI tract and pancreas

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Action: Action: intestinal secretion (water, electrolytes) and motilityintestinal secretion (water, electrolytes) and motility

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Stimulators: fatty acids, acetylcholineStimulators: fatty acids, acetylcholine

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Pancreatic Pancreatic PolypetidePolypetide

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Origin: Islet cells in pancreasOrigin: Islet cells in pancreas

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Action: Action: pancreatic and gallbladder secretionpancreatic and gallbladder secretion

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Stimulators: food, vagal stimulationStimulators: food, vagal stimulation

GiGi

hormoneshormones

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MotilinMotilin

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Origin: various intestinal cellsOrigin: various intestinal cells

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Action: Action: small bowel motilitysmall bowel motility

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Stimulators: duodenal acid, food, vagal inputStimulators: duodenal acid, food, vagal input

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Inhibitors: somatostatin, secretin, pancreatic polypeptideInhibitors: somatostatin, secretin, pancreatic polypeptide

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Erythromycin Erythromycin acts on this receptoracts on this receptor

GiGi

hormoneshormones

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BombesinBombesin

(gastrin(gastrin--releasing peptide)releasing peptide)

•• gastric acid secretion, gastric acid secretion, pancreatic secretion, pancreatic secretion, motilitymotility

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Peptide YYPeptide YY

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Released from TI after fatty mealReleased from TI after fatty meal

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Inhibits acid secretion, pancreatic and gallbladder secretionInhibits acid secretion, pancreatic and gallbladder secretion

QuestionsQuestions

••

Which of the following questions are true or false?Which of the following questions are true or false?

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GIP is released from the duodenum in the presence of GIP is released from the duodenum in the presence of glucose, AAglucose, AA’’s, longs, long--chain fatty acids, and low pH.chain fatty acids, and low pH.

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TRUETRUE••

Glucagon and Peptide YY both decrease GI motility and Glucagon and Peptide YY both decrease GI motility and pancreatic secretionpancreatic secretion

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TRUE TRUE

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VIP causes decreased GI motility and decreased absorption.VIP causes decreased GI motility and decreased absorption.••

FALSEFALSE••

Bombesin results in increased GI motilityBombesin results in increased GI motility

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TRUETRUE••

Pancreatic polypeptide stimulates release of pancreatic Pancreatic polypeptide stimulates release of pancreatic enzymes.enzymes.

••

FALSEFALSE

Transplant MedsTransplant Meds

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Azathioprine (Imuran)Azathioprine (Imuran)••

Inhibits purine synthesis affecting T cellsInhibits purine synthesis affecting T cells

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66--mercaptopurine is active metabolitemercaptopurine is active metabolite

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Side effects: myelosuppressionSide effects: myelosuppression

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Common maintenance for renalCommon maintenance for renal

tx ptstx pts

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Mycophenolate Mycophenolate ((CellceptCellcept))••

Similar in function to AzathioprineSimilar in function to Azathioprine

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Side Side effetseffets: GI intolerance: GI intolerance

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SteroidsSteroids••

Inhibit genes for cytokine synthesis (ILInhibit genes for cytokine synthesis (IL--1, 6) and macrophages1, 6) and macrophages

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Side effects: adrenal suppression, Side effects: adrenal suppression, osteoporsisosteoporsis, hyperglycemia, , hyperglycemia, weight gain, etc.weight gain, etc.

Transplant Transplant medsmeds

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CyclosporinCyclosporin••

Binds cyclosporin protein inhibiting genes for cytokine synthesiBinds cyclosporin protein inhibiting genes for cytokine synthesis (ILs (IL--

2,3,4 and INF2,3,4 and INF--gamma)gamma)

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Side effects: nephrotoxicity, hepatotoxicity, HUS, seizures, ginSide effects: nephrotoxicity, hepatotoxicity, HUS, seizures, gingival gival hyperplasiahyperplasia

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Hepatic metabolism and biliary excretionHepatic metabolism and biliary excretion

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Many drug Many drug interactionsinteractions

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FKFK--506 (Prograf)506 (Prograf)••

Binds FK binding protein; action similar to cyclosporinBinds FK binding protein; action similar to cyclosporin

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Side effects: nephrotoxicity, neurologic and mood changes, HTNSide effects: nephrotoxicity, neurologic and mood changes, HTN

Transplant Transplant medsmeds

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ATGAMATGAM••

Equine polyclonal antibodies against T cells (CD2,3,4,8)Equine polyclonal antibodies against T cells (CD2,3,4,8)

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Used for induction therapyUsed for induction therapy

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Complement dependentComplement dependent

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ThymoglobulinThymoglobulin••

Rabbit polyclonal antibodiesRabbit polyclonal antibodies

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Action similar to ATGAMAction similar to ATGAM

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Often used for induction of immunosuppressionOften used for induction of immunosuppression

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OKT3OKT3••

Monoclonal antibodies that block antigen recognition function ofMonoclonal antibodies that block antigen recognition function of

T cells by binding CD3T cells by binding CD3••

Used for severe rejectionUsed for severe rejection

QestionsQestions

••

All of the following are true regarding Azathioprine All of the following are true regarding Azathioprine except:except:••

66--mercaptopurine is the active metabolitemercaptopurine is the active metabolite

••

The key mechanism is to inhibit genes which regulate The key mechanism is to inhibit genes which regulate cytokine synthesis in T cellscytokine synthesis in T cells

••

Routine Routine CBCCBC’’ss

are necessary while taking this are necessary while taking this

medicationmedication

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This drug is used for maintenance immunosuppressionThis drug is used for maintenance immunosuppression

QuestionsQuestions

••

Which of the following are true or false?Which of the following are true or false?••

OKT3 is a monoclonal antibody used for severe rejectionOKT3 is a monoclonal antibody used for severe rejection••

TRUETRUE

••

FKFK--506 effectively inhibits nucleotide synthesis similar to 506 effectively inhibits nucleotide synthesis similar to AzathioprineAzathioprine

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FALSEFALSE

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Thymoglobulin is a polyclonal antibody made from rabbits Thymoglobulin is a polyclonal antibody made from rabbits often used for induction therapyoften used for induction therapy

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TRUETRUE••

Nephrotoxicity, hepatotoxicity, and neurologic changes are all Nephrotoxicity, hepatotoxicity, and neurologic changes are all common side effects of cyclosporin.common side effects of cyclosporin.

••

TRUE TRUE

rejectionrejection

RejectionRejection

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HypercuteHypercute

RejectionRejection

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Occurs within minutes to hoursOccurs within minutes to hours

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Caused by preformed antibodiesCaused by preformed antibodies

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Results in complement cascade and vessel thrombosisResults in complement cascade and vessel thrombosis

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Need immediate Need immediate retransplantretransplant

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Accelerated RejectionAccelerated Rejection••

Occurs < 1 weekOccurs < 1 week

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Caused by sensitized T cells to donor antigensCaused by sensitized T cells to donor antigens

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Results in secondary immune responseResults in secondary immune response

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Tx: increase immunosuppression with pulse steroids, possibly Tx: increase immunosuppression with pulse steroids, possibly OKT3OKT3

rejectionrejection

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Acute RejectionAcute Rejection••

Occurs within 1 week to 1 monthOccurs within 1 week to 1 month

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Caused by T cells (cytotoxic and Helper T)Caused by T cells (cytotoxic and Helper T)

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Tx: increase immunosuppression, pulse steroids, possibly Tx: increase immunosuppression, pulse steroids, possibly OKT3OKT3

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Chronic RejectionChronic Rejection••

Partly a Type IV hypersensitivity reactionPartly a Type IV hypersensitivity reaction

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Leads to inevitable graft fibrosis and vascular injuryLeads to inevitable graft fibrosis and vascular injury

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Tx: increase existing immunosuppression Tx: increase existing immunosuppression ––

no cureno cure

questionsquestions

••

True or False:True or False:••

Pulse steroids and OKT3 are used for acute rejection.Pulse steroids and OKT3 are used for acute rejection.

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TRUETRUE

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Hyperacute rejection is secondary to sensitized T cells Hyperacute rejection is secondary to sensitized T cells against donor antigens.against donor antigens.

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FALSEFALSE

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Chronic rejection manifests in graft thrombosis and Chronic rejection manifests in graft thrombosis and vascular injuryvascular injury

••

TRUETRUE

QuestionsQuestions

••

After receiving a renal transplant, a patient is started After receiving a renal transplant, a patient is started on a regimen of tacrolimus, corticosteroids, on a regimen of tacrolimus, corticosteroids, mycophenolate mofetil, and trimethoprimmycophenolate mofetil, and trimethoprim--sulfa. sulfa. Two weeks after transplant, she develops seizures. Two weeks after transplant, she develops seizures. The most likely cause of these symptoms is:The most likely cause of these symptoms is:••

Tacrolimus toxicityTacrolimus toxicity

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Corticosteroid toxicityCorticosteroid toxicity

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Mycophenolic acid toxicityMycophenolic acid toxicity

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RejectionRejection

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MeningitisMeningitis

questionsquestions

••

Which of the following statements about acute Which of the following statements about acute rejection is NOT true?rejection is NOT true?••

It is TIt is T--cell mediatedcell mediated

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It is related to organIt is related to organ--host human leukocyte antigen host human leukocyte antigen disparitydisparity

••

Treatment can save the grafted organ in 90% to 95% of Treatment can save the grafted organ in 90% to 95% of casescases

••

It does not occur with living related donors.It does not occur with living related donors.

••

It is associated with an increased risk of chronic It is associated with an increased risk of chronic rejectionrejection

HematologyHematology

hematologyhematology

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CoagulationCoagulation••

All factors made in liver except VIII (endothelium)All factors made in liver except VIII (endothelium)

••

Vitamin KVitamin K--dependent factors:dependent factors:••

II, VII, IX, X, protein C and SII, VII, IX, X, protein C and S

••

Prostacyclin Prostacyclin (PGI(PGI

22

): ): ••

From endotheliumFrom endothelium

••

Decreases platelet aggregation, causes vasodilationDecreases platelet aggregation, causes vasodilation

••

Thromboxane Thromboxane (TXA(TXA

22

): ): ••

From plateletsFrom platelets

••

Causes platelet aggregation and vasoconstrictionCauses platelet aggregation and vasoconstriction

hematologyhematology

••

Von WillebrandVon Willebrand’’s diseases disease••

Most common congenital disorderMost common congenital disorder

••

Type 1 and 2 autosomal dominant; 3 recessiveType 1 and 2 autosomal dominant; 3 recessive

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vWF links Gp1b receptor on platelet to collagenvWF links Gp1b receptor on platelet to collagen

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PTPT

normal; normal; PTT PTT normal or highnormal or high

••

Have long bleeding time (ristocetin test)Have long bleeding time (ristocetin test)

••

Type 1 and 3 from reduced quantityType 1 and 3 from reduced quantity

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Treat with cryo, DDAVPTreat with cryo, DDAVP

••

Type 2 is defect in vWF functionType 2 is defect in vWF function

••

Treat with cryoTreat with cryo

hematologyhematology

••

CryoprecipitateCryoprecipitate••

Highest concentration of Highest concentration of vWF vWF and VIIIand VIII

••

Used in von Used in von WillebrandsWillebrands

disease (especially type 2) disease (especially type 2) and and

Hemophilia AHemophilia A

••

FFPFFP••

Contains all factors including protein C, S, and AT3Contains all factors including protein C, S, and AT3

••

DDAVPDDAVP••

Cause release of VIII and vWF from Cause release of VIII and vWF from endotheliumendothelium

••

Only effective in vWF type 1 and 3Only effective in vWF type 1 and 3

hematologyhematology

••

Platelet disordersPlatelet disorders••

Clinical Signs: bruising, epistaxis, petechiae, purpuraClinical Signs: bruising, epistaxis, petechiae, purpura

••

Acquired Acquired thromocytopeniathromocytopenia: heparin, H2 blockers: heparin, H2 blockers

••

GlanzmannGlanzmann’’s s thrombocytopenia: thrombocytopenia:

••

GpIIbGpIIb/IIIa receptor deficiency on platelets (can/IIIa receptor deficiency on platelets (can’’t bind to t bind to each othereach other

through through fibrin)fibrin)

••

Tx: plateletsTx: platelets

••

Bernard SoulierBernard Soulier••

GpIbGpIb

receptor deficiencyreceptor deficiency

((cancan’’t bind collagen t bind collagen --

vWF)vWF)

••

Tx: plateletsTx: platelets

hematologyhematology

••

Hypercoagulability (Hypercoagulability (virchowvirchow’’ss

triad)triad)

••

Leiden factor: Leiden factor:

••

30% of spontaneous 30% of spontaneous DVTDVT’’ss

••

Most common congenital hypercoagulabilityMost common congenital hypercoagulability

••

Factor V resistant to Factor V resistant to degredationdegredation

by protein Cby protein C

••

HyperhomocysteinuriaHyperhomocysteinuria

••

10% of spontaneous 10% of spontaneous DVTDVT’’ss

••

Treat with folate and B12Treat with folate and B12

••

Prothrombin gene defect (5%)Prothrombin gene defect (5%)

••

Protein C or S deficiency (5%)Protein C or S deficiency (5%)

••

AT3 deficiency (2AT3 deficiency (2--3%)3%)

questionquestion

••

HypercoagulabilityHypercoagulability••

Acquired hypercoagulabilityAcquired hypercoagulability

••

TobaccoTobacco

••

MalignancyMalignancy

••

PregnancyPregnancy

••

Inflammatory statesInflammatory states

••

InfectionsInfections

••

PostPost--opop

••

OCPOCP’’ss

••

Myeloproliferative disordersMyeloproliferative disorders

questionquestion

••

All of the following are true regarding von All of the following are true regarding von WillebrandsWillebrands

disease except:disease except:••

Von Von willebrandwillebrand

factor links Gp1b receptor on platelets to factor links Gp1b receptor on platelets to

collagencollagen

••

Patients have long bleeding time (ristocetin test) and INR Patients have long bleeding time (ristocetin test) and INR isis

elevatedelevated

••

Treatment is with cryoprecipitate and DDAVPTreatment is with cryoprecipitate and DDAVP

••

It is the most common congenital bleeding disorderIt is the most common congenital bleeding disorder

••

Types 1 and 3 are caused by reduced function; Type 2 is Types 1 and 3 are caused by reduced function; Type 2 is from reduced quantityfrom reduced quantity

QuestionsQuestions

••

Which of the following are true or false:Which of the following are true or false:

••

Calcium, phospholipids, prothrombin,Calcium, phospholipids, prothrombin,

factor V, and factor V, and factor Xa factor Xa are all needed for the formation of thrombin.are all needed for the formation of thrombin.

••

TRUETRUE

••

DDAVP causes release of factor VIII and DDAVP causes release of factor VIII and vWfvWf

from vascular from vascular endotheliumendothelium

••

TRUETRUE

••

Leiden mutation results from decreased production of factor V.Leiden mutation results from decreased production of factor V.

••

FALSEFALSE

••

Heparin activates AT3 which inhibits II, IX, X, and XIHeparin activates AT3 which inhibits II, IX, X, and XI

••

TRUE TRUE