Chapter 73 / Transplant Surgery 671

Third-degree A-V block? Complete A-V dissociation; random P wave and QRS

MISCELLANEOUS

What is Mondor’s disease?

What is a VAD?

How does an IABP work?

What electrolyte must be monitored during diuresis after CPB?

Thrombophlebitis of the thoracoepigastric veins

Ventricular Assist Device

IntraAortic Balloon Pump has a balloon tip resting in the aorta

Balloon inflates in diastole, increasing diastolic BP and coronary blood flow; in systole the balloon deflates,

creating a negative pressure, lowering afterload, and increasing systolic BP

K

How is extent/progress of	I’s and O’s, CXR, JVD, edema, daily
postbypass diuresis followed?	weight
What is an Austin Flint	Diastolic murmur of AI secondary to
murmur?	regurgitant turbulent flow
Where is the least oxygenated	Coronary sinus
blood in the body?
What is the most common	Metastasis
cause of a cardiac tumor?

C h a p t e r 73	Transplant Surgery
Define the following terms:
Autograft	Same individual is both donor and
	recipient
Isograft	Donor and recipient are genetically
	identical (identical twins)

672 Section III / Subspecialty Surgery
Allograft	Donor and recipient are genetically
	dissimilar, but of the same species
Xenograft	Donor and recipient belong to different
	species
Orthotopic	Donor organ is placed in normal
	anatomic position (liver, heart)
Heterotopic	Donor organ is placed in a different site
	than the normal anatomic position
	(kidney, pancreas)
Paratopic	Donor organ is placed close to original
	organ
Chimerism	Sharing cells between the graft and donor
BASIC IMMUNOLOGY
What are histocompatibility	Distinct (genetically inherited) cell
antigens?	surface proteins of the human leukocyte
	antigen system (HLA)
Why are they important?	They are targets (class I antigens) and
	initiators (class II antigens) of immune
	response to donor tissue (i.e.,
	distinguishing self from nonself)

Which cells have class I antigens?

Which cells have class II antigens?

What are the gene products of MHC called in humans?

What is the location of the MHC complex?

What is a haplotype?

All nucleated cells (Think: class 1 ALL cells and thus “ONE for ALL”)

Macrophages, monocytes, B cells, activated T cells, endothelial cells

HLA (Human Leukocyte Antigen)

Short arm of chromosome 6

Combination of HLA genes on a chromosome inherited from one parent; therefore, two siblings have a 25% chance of being “haploidentical”

	Chapter 73 / Transplant Surgery 673
Does HLA matching matter	With recent improvements in
in organ transplantation?	immunosuppression (i.e., cyclosporine),
	the effect is largely obscured, but it still
	does matter; the most important ones to
	match in order to improve renal allograft
	survival are HAL-B and HLA-DR
CELLS
T CELLS
What is the source?	Thymus
What is the function?	Cell-mediated immunity/rejection
What are the types?	Th (CD4): helper T—help B cells
	become plasma cells
	Ts (CD8): suppressor T—regulate
	immune response
	Tc (CD8): cytotoxic T—kill cell by direct
	contact
B CELLS
What is the function?	Humoral immunity
What is the cell type that	B cells differentiate into plasma cells
produces antibodies?
MACROPHAGE
What is it?	Monocyte in parenchymal tissue
What is its function?	Processes foreign protein and presents it
	to lymphocytes
What is it also known as?	Antigen-Presenting Cell (APC)
Briefly describe the events	1. Macrophage engulfs antigen and
leading to antibody	presents it to Th cells; the
production.	macrophage produces IL-1
	2. Th cells then produce IL-2, and the
	Th cells proliferate
	3. Th cells then activate (via IL-4) B cells
	that differentiate into plasma cells,
	which produce antibodies against the
	antigen presented

674 Section III / Subspecialty Surgery

IMMUNOSUPPRESSION

Who needs to be	All recipients (except autograft or isograft)
immunosuppressed?
What are the major drugs	Triple therapy: corticosteroids,
used for immunosuppression?	azathioprine, cyclosporine/tacrolimus
What are the other drugs?	OKT3, ATGAM, mycophenolate
What is the advantage of	Employs three immunosuppressive drugs;
“triple therapy”?	therefore, a lower dose of each can be used,
	decreasing the toxic side effects of each
What is “induction therapy”?	High doses of immunosuppressive drugs
	to “induce” immunosuppression
CORTICOSTEROIDS
Which is most commonly	Prednisone
used in transplants?
How does it function?	Primarily blocks production of IL-1 by
	macrophage and stabilizes lysosomal
	membrane of macrophage
What is the associated	“Cushingoid,” alopecia, striae, HTN,
toxicity?	diabetes, pancreatitis, ulcer disease,
	osteomalacia, aseptic necrosis (especially
	of the femoral head)
What is the relative
potency of the following
corticosteroids:
Cortisol?	1
Prednisone?	4
Methylprednisolone?	5
Dexamethasone?	25

AZATHIOPRINE (AZA [IMURAN®])

How does it function?	Prodrug that is cleaved into
	mercaptopurine; inhibits synthesis of DNA
	and RNA, leading to decreased cellular
	(T/B cells) production

What is the associated toxicity?

When should a lower dose of AZA be administered?

What is the associated drug interaction?

CYCLOSPORINE (CSA)

Chapter 73 / Transplant Surgery 675

Toxic to bone marrow (leukopenia thrombocytopenia), hepatotoxic, associated with pancreatitis

When WBC is 4

Decrease dose if patient is also on allopurinol, because allopurinol inhibits the enzyme xanthine oxidase, which

is necessary for the breakdown of azathioprine

What is its function?	“Calcineurin inhibitor” inhibits
	production of IL-2 by Th cells
What is the associated	Toxicity for cyclosporine includes the
toxicity?	11 “H’s” and three “N’s”: Hepatitis,
	Hypertrichosis, gingival Hyperplasia,
	Hyperlipidemia (worse than FK),
	Hyperglycemia, Hypertension (worse
	than FK), Hemolytic uremic syndrome,
	Hyperkalemia, Hypercalcemia,
	Hypomagnesemia, Hyperuricemia,
	Nephrotoxicity, Neurotoxicity (headache,
	tremor), Neoplasia (lymphoma, KS,
	squamous cell skin cancers)
What drugs increase CSA	Diltiazem
levels?	Ketoconazole
	Erythromycin, fluconazole, ranitidine
What drugs decrease CSA	By inducing the p450 system: dilantin,
levels?	Tegretol®, rifampin, isoniazid, barbiturates
What are the drugs of	Clonidine, calcium channel blockers
choice for HTN from CSA?
ATGAM/ANTITHYMOCYTE GLOBULIN
How does it function?	Antibody against thymocytes,
	lymphocytes (polyclonal)
When is it typically used?	For induction

676 Section III / Subspecialty Surgery
What is the associated	Thrombocytopenia, leukopenia, serum
toxicity?	sickness, rigors, fever, anaphylaxis,
	increased risk of viral infection, arthralgia
OKT3
How does it work?	MONOclonal antibody that binds CD3
	receptor (on T cells)
What is a major problem	Blocking antibodies develop, and OKT3
with multiple doses?	is less effective each time it is used
What are basiliximab and	Anti-CD25 monoclonal antibodies
daclizumab?
TACROLIMUS
What is tacrolimus also	Prograf®(FK506)
known as?
How does it work?	Similar to CSA—“calcineurin inhibitor,”
	blocks IL-2 receptor expression, inhibits
	T cells
What is its potency	100 more potent than CSA
compared to CSA?
What are its side effects?	Nephrotoxicity and CNS toxicity
	(tremor, seizure, parasthesia, coma),
	hyperkalemia, alopecia, diabetes
SIROLIMUS
What is sirolimus also	Rapamycin, Rapamune®
known as?
How does it work?	Like CSA and tacrolimus, it does not
	bind to and inhibit calcineurin; rather, it
	blocks T-cell signaling
Toxicity?	Hypertriglyceridemia, thrombocytopenia,
	wound/healing problems, anemia, oral
	ulcers
MYCOPHENOLATE MOFETIL (MMF)
What is MMF also known as?	CellCept®