Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2704_Библиотеки_им_академика_М_И_Перельмана
.pdf
340 SECTION V Renal Disease
Antigen-presenting cellAntigen-presenting cell
CD80/CD86CD80/CD86
Belatacept
Belatacept
CD28CD28
SirolimusSirolimus
TABLE 30.3 Comparison of Donor Sources for Kidney Transplantation
Advantages Disadvantages
Living Donor
Waiting time for transplant reduced Small potential postoperative risks for the donor
Sequelae of long-term dialysis avoided Small potential long-term risk of kidney function decline in the donor
Elective surgical procedure Requirement of a willing, medically suitable donor
Better early graft function with shorter hospitalization
Better short-term and long-term success
Deceased Donor
Availability to any recipient Waiting time variable
Availability of other organs for combined transplants (i.e., kidney-pancreas
transplant)
Availability of vascular conduits for complex vascular reconstruction Higher rates of delayed or slow graft function
OKT3OKT3
X
X
CostimulationCostimulation
XX
CD3CD3
Operation performed urgently
Short-term and long-term success not as good as from a living donor
MHCMHC
AntigenAntigen
XX
TCRTCR ATGATG
Cyclosporine
Cyclosporine
Tacrolimus
Tacrolimus
IL-2IL-2
Anti-CD25Anti-CD25
XX
CD25CD25
SteroidsSteroids
XX
NFκBNFκB
T cellT cell
Fig. 30.5 Pathways of T-cell activation and site of action of immunosuppressive agents. ATG, Antithymo-
cyte globulin; AZA, azathioprine; IL, interleukin; MHC, major histocompatibility complex; MMF, mycoplasma
membrane fraction; MTOR, mammalian target of rapamycin; NFAT, nuclear factor of activated T cells; TCR,
T-cell receptor.
CalcineurinCalcineurin
NFATNFAT
IL-2 geneIL-2 gene
Immunosuppressant drug therapy. Achieving adequate
immunosuppression while minimizing drug toxicity and the risk of
infection is at the heart of the success of kidney transplantation. All
protocols for immunosuppression aim to inhibit the T lymphocyte,
targeting different sites or pathways in the 3-signal model of T-cell
activation and proliferation. The mechanisms of action of commonly
used immunosuppressants is illustrated in Fig. 30.5. Additionally,
antibody-directed therapy is usually employed in those who require
desensitization due to preexisting HLA or blood group antibodies.
Induction immunosuppression is administered at the time of transplant and the immediate postoperative period in the form of high-dose
steroids, with or without a T lymphocyte–depleting agent such as antithymocyte globulin or a nondepleting agent such as basiliximab (an
interleukin-2 inhibitor). Maintenance immunosuppression is initiated
postoperatively and is composed of at least two drugs, with or without
corticosteroids. In the United States, the most common regimen at the
time of discharge from the hospital after a transplant is tacrolimus,
mycophenolate, and prednisone.
XX
mTORmTOR
G
1G1
MM
SS
AZA
AZA
XX
MMF
MMF
The hepatic cytochrome P-450 system is essential for cyclosporine,
tacrolimus, and mTOR inhibitor metabolism. Significant changes in the
levels of these drugs may occur when patients start or discontinue taking
any of several drugs that can induce or inhibit this system. Therefore,
evaluation for drug-drug interactions is critical to prevent toxic or even
subtherapeutic effects of either the immunosuppressant drug or the
other prescribed therapy. Cyclosporine exerts its activity by initially binding to cyclophilin. The cyclosporine-cyclophilin complex subsequently
inhibits calcineurin, a calcium-dependent phosphatase that dephosphorylates nuclear factor of activated T cells (NFAT). The inhibition
of NFAT dephosphorylation prevents transcription of T-cell activation
genes. Side effects of cyclosporine include hypertension, hyperkalemia,
hypomagnesemia, exacerbation of gout, dyslipidemia, hypertrichosis, and gingival hypertrophy. Tacrolimus has a mechanism of action
and side-effect profile like those of cyclosporine. However, it binds to
FK-binding protein instead of cyclophilin. It also has additional problems of hyperglycemia and an increased tendency toward neurotoxicity.
Rather than causing hypertrichosis, it causes alopecia. Both cyclosporine
CHAPTER 30 Chronic Kidney Disease
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
341
and tacrolimus can cause calcineurin inhibitor nephrotoxicity, and this is
often related to afferent arteriolar vasoconstriction leading to decreased
glomerular blood flow. Nephrotoxicity can be acute or chronic and ultimately may contribute to chronic allograft nephropathy and graft loss.
Mycophenolate mofetil or mycophenolic acid specifically inhibits
T-lymphocyte and B-lymphocyte proliferation by interfering with
purine synthesis and thus DNA synthesis. Side effects include leukopenia, anemia, and upper and lower gastrointestinal symptoms.
Sirolimus and everolimus bind to FK-binding protein and subsequently inhibit mTOR, thus blocking the phosphorylation of p70(s6)
kinase and the eukaryotic initiation factor 4E–binding protein,
PHAS-I. This action leads to the dampening of cytokine and growth
factor activity on T, B, and nonimmune cells. The major side effects
are thrombocytopenia, proteinuria, impaired wound healing, and dyslipidemia. mTOR inhibitors can also cause mouth ulcerations, lymphedema, and pneumonitis.
Due to the persistence of episodes of rejection and graft loss over
time, novel immunosuppressive agents continue to be developed. Most
recently, belatacept, a fusion protein that inhibits T-cell activation by
blocking the CD80 and CD86 sites on antigen presenting cells, has
been shown to confer superior long-term graft function compared to a
cyclosporine-based maintenance regimen. This is despite an increased
risk of developing early severe acute rejection episodes. Belatacept is
administered intravenously and its most serious adverse effect is an
increased incidence of post-transplant lymphoproliferative disorder
(PTLD) compared to cyclosporine. It is therefore contraindicated in
recipients who have not been exposed to Epstein-Barr virus because
these patients are at an already higher risk for PTLD at baseline.
Acute rejection. Clinically, acute rejection is detected by a rise in
serum creatinine or the development of new proteinuria. In severe
cases, graft tenderness and oliguria can occur. Acute cellular rejection
occurs when T lymphocytes recognize foreign antigens, especially
when presented in association with class II histocompatibility
antigens. This prompts lymphocyte activation and subsequent
invasion of the tubulointerstitium, and in severe cases the blood vessel
wall, by activated cytotoxic lymphocytes, resulting in tubulitis and/
or endothelialitis. This type of rejection is usually treated with highdose steroids with or without antithymocyte globulin depending on
the severity of the rejection and the initial response to steroid therapy.
Acute humoral rejection usually occurs in the presence of preexisting
or de novo donor-specific HLA antibodies and manifests in the
transplanted kidney as microvascular inflammation with or without
C4d staining on immunofluorescence. This type of rejection is usually
treated with intravenous immune globulin and plasmapheresis, with
or without B-cell directed therapy.
Post-transplantation infection. Infection is second only to
cardiovascular disease as the leading cause of mortality in kidney
transplant recipients. Prophylaxis is used immediately after
kidney transplantation to prevent opportunistic infections such as
Pneumocystis jirovecii pneumonia, cytomegalovirus infection, herpes
simplex virus infection, and Candida infections. In addition to
common community-acquired bacterial and viral infections, kidney
transplant recipients are also susceptible to numerous viral, fungal,
and other opportunistic infections that normally do not cause severe
illness in the immunocompetent host.
Post-transplantation malignant disease. Immunosuppression
increases the risk for developing malignant disease. Skin cancer (mostly
squamous cell) has the highest incidence in transplant recipients
compared with all other types of malignancy. With continuous
surveillance and aggressive management, metastasis from skin cancers
is rare. Transplant recipients are also at increased risk for developing
non-Hodgkin lymphoma and Kaposi sarcoma. In addition to ageappropriate screening, cancer surveillance should be an essential part
of post-transplantation care.
PROGNOSIS
The prognosis of CKD varies depending upon the underlying cause, its
severity at presentation, and the response to therapy. Yet, it is important to recognize that CKD in general is a significant risk factor for cardiovascular disease and death. Mortality from cardiovascular disease
in CKD patients, especially those with stage 3 to 5 disease, is 3.5 times
that of an age-matched population (E-Fig. 30.8) and accounts for more
than 50% of the deaths in ESRD patients. Research to understand the
underlying mechanisms and final pathway, as well as those specific to
patients with unique characteristics, will be necessary to advance our
efforts to reduce related risks and cure kidney disease.
SUGGESTED READINGS
Abbate M, Remuzzi G: Progression of renal insufficiency: mechanisms.
In Massry SG, Glassock RJ, editors: Massry and Glassock’s textbook of
nephrology, 4th ed, Philadelphia, 2001, Lippincott, Williams & Wilkins, pp
1210–1217.
Coresh J, Selvin E, Stevens LA, et al.: Prevalence of chronic kidney disease in
the United States, JAMA 298:2038–2047, 2007.
Durrbach A, Francois H, Beaudreuil S, et al.: Advances in immunosuppression
for renal transplantation, Nat Rev Nephrol 6:160–167, 2010.
Fishman JA, AST Infectious Disease Community of Practice: Introduction:
infection in solid organ transplant recipients, Am J Transplant(Suppl
4)S3–6, 2009.
Halloran PF: Drug therapy: immunosuppressive drugs for kidney
transplantation, N Engl J Med 351:2715–2729, 2004.
Kidney Disease: Improving Global Outcomes(KDIGO) CKD Work
Group: KDIGO 2012 clinical practice guideline for the evaluation
and management of chronic kidney disease, Kidney Inter Suppl 3:1–150,
2013.
Luke RG: Chronic renal failure. In Goldman L, Bennett JC, editors: Cecil
textbook of medicine, 21st ed, Philadelphia, 2000, WB Saunders, pp
571–577.
National Kidney Foundation: KDOQI clinical practice guidelines and clinical
practice recommendations for diabetes and chronic kidney disease, Am J
Kidney Dis 49(2 Suppl 2):S12–S154, 2007.
Sarafidis P, Ferro CJ, Morales E, et al. SGLT-2 inhibitors and GLP-1 receptor
agonists for nephroprotection and cardioprotection in patients with
diabetes mellitus and chronic kidney disease. A consensus statement by
the EURECA-m and the DIABESITY working groups of the ERA-EDTA,
Nephrology Dialysis Transplantation 34:208–230, 2019.
Sarnak MJ, Levey AS, Schoolwerth AC, et al.: Kidney disease as a risk factor
for development of cardiovascular disease: A statement from the American
heart association councils on kidney in cardiovascular disease, high blood
pressure research, clinical cardiology, and epidemiology and prevention,
Circulation 108:2154–2169, 2003.
U.S. Renal Data System, USRDS 2018 Annual Data Report: Atlas of chronic
kidney disease and end-stage renal disease in the United States, National
Institutes of Health, Bethesda, MD, 2018, National Institute of Diabetes
and Digestive and Kidney Diseases.
Vincenti F, Rostaing L, Grinyo J, et al.: Belatacept and long-term outcomes in
kidney transplantation, N Engl J Med 374(4):333–343, 2016.
Voora S, Adey DB: Management of kidney transplant recipients by general
nephrologists: core curriculum 2019, Am J Kidney Dis 73(6):866–879,
2019.
100
10
Age (years)
Annual mortality (%)
1
GP Male
0.1
0.01
25–34 35–44 45–54 55–64 65–74 75–84 85
E-Fig. 30.8 Cardiovascular mortality in the general population (GP)
and in patients receiving dialysis. (From National Kidney Foundation:
K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification, Am J Kidney Dis 39[2 Suppl 1]:S1S266, 2002.)
GP Female
GP Black
GP White
Dialysis Male
Dialysis Female
Dialysis Black
Dialysis White
CHAPTER 30 Chronic Kidney Disease
341.e1
SECTION VI
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Gastrointestinal Disease
31 Common Clinical Manifestations of
Gastrointestinal Disease: Abdominal
Pain, 343
32 Common Clinical Manifestations of
Gastrointestinal Disease: Gastrointestinal
Hemorrhage, 347
33 Common Clinical Manifestations
of Gastrointestinal Disease:
Malabsorption, 351
34 Common Clinical Manifestations of
Gastrointestinal Disease: Diarrhea, 358
35 Endoscopic and Imaging Procedures, 363
36 Esophageal Disorders, 370
37 Diseases of the Stomach and
Duodenum, 379
38 Inflammatory Bowel Disease, 392
39 Diseases of the Pancreas, 402
342
31
Common Clinical Manifestations of
Gastrointestinal Disease: Abdominal
Pain
Charles M. Bliss, Jr.
DEFINITION AND EPIDEMIOLOGY
Abdominal pain is a frequent manifestation of intra-abdominal disease. However, abdominal pain is difficult to localize or grade because
the sensation of pain often is colored by emotional and physical factors. Abdominal pain may be classified as acute or chronic. Acute
pain occurs suddenly and more often suggests serious physiologic
alterations. Chronic pain may be present for several months; although
it does not mandate immediate attention, chronic pain may lead to
prolonged evaluation. According to a recent survey of 71,812 patients,
25% of the respondents reported abdominal pain within the past week.
Appropriate evaluation of abdominal pain requires knowledge of pain
mechanisms, close attention to history and physical examination findings, and recognition of important accompanying symptoms as well
as awareness of the strengths and weaknesses of the tests that might
be used.
PHYSIOLOGY
Abdominal pain results from stimulation of receptors specific for
thermal, mechanical, or chemical stimuli. Once these receptors are
excited, pain impulses travel through sympathetic fibers. Abdominal
pain can be characterized as somatic or visceral. Somatic pain originates from the abdominal wall and parietal peritoneum, whereas
visceral pain originates in internal organs and from the visceral peritoneum. Two types of neurons carry pain: A fibers, which have rapid
conduction, and C fibers, which have slow conduction. Most visceral
neurons are of the C type, and the pain resulting from their stimulation tends to be variable with regard to sensation and localization.
In contrast, both A and C fibers originate from the parietal peritoneum and abdominal wall, and somatic pain tends to be sharp and
distinctly localized.
Because of this pattern of innervation, abdominal viscera are
not sensitive to cutting, tearing, burning, or crushing. However,
visceral pain results from stretching of the walls of hollow organs
or of the capsule of solid organs, as well as from inflammation or
ischemia.
CAUSES OF ABDOMINAL PAIN
Multiple intra-abdominal and extra-abdominal disorders can produce
abdominal pain. Distinguishing acute from chronic symptoms is helpful. The approach varies with each specific cause, but acute abdominal
pain usually demands prompt intervention.
CLINICAL PRESENTATION
History
The differential diagnosis of abdominal pain, whether acute or chronic,
requires thorough history taking with regard to pain characteristics,
location and radiation, timing, and the presence of any accompanying
symptoms. Recognition of characteristic patterns is essential to narrowing the differential diagnosis.
Pain location often indicates the organ responsible for the problem. For instance, epigastric pain is usually typical of peptic ulcer or
dyspepsia, whereas right upper quadrant pain is more suggestive of
cholecystitis and other biliary disorders. Early in the course of illness, pain may be perceived in one location and subsequently felt
in another; this pattern of progression may be suggestive of specific
pain syndromes. In acute cases, abdominal pain tends to be sharp and
severe. The pain of a perforated viscus is intense, and the pain from a
dissecting aneurysm may be described as tearing or crushing. Chronic
pain may be less severe; pain from irritable bowel or dyspepsia is
constant and dull, and the pain of chronic peptic ulcer is described
as gnawing or hunger pain. The pattern of pain relief is helpful for
diagnosing some conditions. The physician should also inquire about
whether the pain is steady or intermittent and whether it occurs at
night. For nocturnal pain, a distinction should be made between pain
that awakens the patient and pain that is felt when the patient wakes
up for other reasons.
Table 31.1 outlines characteristics, location, and radiation of pain
for a few common acute and chronic abdominal conditions.
Physical Examination
Examination of the abdomen provides valuable clues to the diagnosis,
but the examination should start with the general appearance of the
patient. A patient who is writhing in bed and unable to find a comfortable position may be suffering from obstruction. In contrast, a patient
lying with the lower extremities flexed and avoiding any motion may
be suffering from peritonitis because movement makes peritoneal pain
worse. Abdominal distention indicates obstruction or ascites. Visual
inspection for peristalsis is helpful for the diagnosis of small bowel
obstruction, but this sign is present only in the early stages. Focal areas
of distention may indicate hernias; notice should also be taken of any
scars from prior surgeries.
Auscultation should be performed in several areas to evaluate the
timbre and pattern of bowel sounds and to search for bruits or hums.
Absence of bowel sounds suggests ileus, whereas the presence of hyperactive, high-pitched sounds may indicate obstruction. Multiple bruits
343
344 SECTION VI Gastrointestinal Disease
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
TABLE 31.1 Key Abdominal Pain Syndromes
Condition Type Location Radiation
Acute Abdominal Pain
Appendicitis Crampy, steady Periumbilical, RLQ Back
Cholecystitis Intermittent, steady Epigastric, RUQ Right scapula
Pancreatitis Steady Epigastric,
periumbilical
Perforation Sudden, severe Epigastric Entire abdomen
Obstruction Crampy Periumbilical Back
Infarction Severe, diffuse Periumbilical Entire abdomen
Chronic Abdominal Pain
Esophagitis Burning Retrosternal Left arm, back
Peptic ulcer Gnawing Epigastric Back
Dyspepsia Bloating, dull Epigastric None
IBS Crampy LLQ, RLQ None
IBS, Irritable bowel syndrome; LLQ, left lower quadrant; RLQ, right
lower quadrant; RUQ, right upper quadrant.
Back
alert the examiner to the possibility of significant vascular disease, suggesting ischemia.
The abdomen should be palpated gently, starting in an area away
from the pain. The examiner searches for areas of localized tenderness
and rebound as well as for masses and enlarged organs. Percussion is
performed to identify the size of organs or to determine the presence of
ascites. Pain on percussion of the abdomen indicates peritoneal reaction, as does severe rebound tenderness.
A rectal examination is important for identifying a rectal tumor in
the case of colon obstruction or tenderness high in the rectum in acute
appendicitis. A pelvic examination should be performed in women to
rule out pelvic inflammatory disease, or masses.
ACUTE ABDOMEN
The evaluation of a patient with an acute abdomen is a challenge in
medical practice. The acute abdomen is caused by sudden inflammation, perforation, obstruction, or infarction of an intra-abdominal
organ. The urgent question to be answered is whether immediate surgery is needed; a quick but complete evaluation is necessary to avoid
undue delay in intervention for patients who require surgery. The physician must assess for abdominal tenderness, rebound, and guarding.
Early surgical consultation should be obtained, even in doubtful cases,
rather than awaiting confirmation of the diagnosis via laboratory or
radiologic studies. However, many extra-abdominal conditions such
as pneumonia, myocardial infarction, nephrolithiasis, and metabolic
disorders can cause acute abdominal pain.
In some instances of the acute abdomen in its early stages, there are
few findings. The examiner should be aware that patients with benign
chronic conditions may have severe pain at presentation that is out of
proportion to any physical findings. The context provided by the medical history, particularly previous abdominal surgery, is very valuable.
Indeed, a patient with sudden crampy pain and abdominal distention
may have an intestinal obstruction caused by adhesions or an incarcerated hernia. Therefore, examination of the entire patient, looking for
jaundice, skin lesions, evidence of prior surgery, or evidence of chronic
liver disease, is important.
In evaluating a patient with acute abdominal symptoms, a complete
blood cell count with differential, a urinalysis, and measurements of
serum amylase, lipase, bilirubin, and electrolytes are necessary components of the laboratory examination. Additional studies may be
done but usually do not aid in the rapid decision making required.
An elevated white blood cell count may indicate inflammatory disease,
and extremely high values are typical of acute intestinal ischemia. An
elevated serum amylase concentration usually indicates acute pancreatitis, although a perforated ulcer or mesenteric thrombosis can also
cause hyperamylasemia.
Radiographic examination with an abdominal film is important
to reveal the intra-abdominal gas pattern, and an upright film that
includes the diaphragm or a left lateral decubitus film may identify intra-abdominal air suggesting perforation of a hollow viscus.
Ultrasonography can be helpful in the diagnosis of acute cholecystitis
or appendicitis. Computed tomography (CT) scans have become more
helpful with technologic improvements in scanners; early CT scans
allow prompt diagnosis of sometimes unsuspected abdominal diseases.
Examination with a radiopaque medium should be used judiciously,
especially if surgery is anticipated. E-Figs. 31.1 through 31.4 are CT
images of appendicitis, diverticulitis, pancreatitis, and ulcerative colitis, respectively.
CHRONIC ABDOMINAL PAIN
In the evaluation of chronic abdominal pain, it can be challenging to
distinguish between organic pain resulting from a specific pathologic
process and functional pain. The location and characteristics of pain,
as already discussed, serve as important guides, as do other accompanying symptoms. The presence of postprandial nausea and vomiting
suggests chronic peptic ulcer, disorders of gastric emptying, or outlet
obstruction. Documentation of weight loss mandates the search for an
organic cause, such as inflammatory bowel disease or celiac disease. If
anorexia accompanies weight loss, particularly in elderly patients, cancer must be excluded. If no cancer can be found and all objective tests
are normal, the possibility of chronic depression must be entertained.
The most frequent causes of chronic abdominal pain are functional.
Dyspepsia is characterized by chronic intermittent epigastric discomfort, sometimes accompanied by nausea or bloating. These symptoms
are not always relieved by acid suppression and may be the result of
an underlying motor disorder. Furthermore, when Helicobacter pylori
is found in a patient with dyspeptic symptoms, its eradication may
not necessarily lead to the resolution of symptoms. Controversy exists
regarding the most effective strategy for the treatment of dyspepsia
when H. pylori organisms are found in the absence of peptic ulcer
disease.
Irritable bowel syndrome (IBS) is a very common disorder.
Estimates are that 15% of Americans suffer from IBS on a regular basis
and that 40% to 50% of referrals to gastroenterologists are related to
IBS. The syndrome consists of abdominal distention, flatulence, and
disordered bowel function. There are two important variants of IBS:
constipation predominant IBS (IBS-C) is characterized by pain in
the setting of constipation, and diarrhea predominant IBS (IBS-D)
involves pain in the setting of diarrhea. IBS with both diarrhea and
constipation is sometimes denoted as IBS mixed. The abdominal pain
of IBS tends to be in the left lower quadrant, but it can be located elsewhere or be more generalized. Any patient with weight loss, anemia,
nocturnal symptoms, steatorrhea, or onset of symptoms after age 50
years should be evaluated carefully for organic disease because these
symptoms are not associated with IBS.
The Rome criteria, developed for research studies, may be
helpful in the diagnosis of IBS. These criteria include pain that is
associated with change in bowel habits, relieved with defecation,
or accompanied by distention or bloating. Patients are reassured,
counseled, and treated with anticholinergic agents and stool softeners. Although serotonin (5-HT) agonists such as alosetron and
CHAPTER 31 Common Clinical Manifestations of Gastrointestinal Disease: Abdominal Pain
344.e1
E-Fig. 31.1 Computed tomographic image of acute appendicitis, with
evidence of edema and surrounding fat stranding. (Courtesy Jorge
Soto, MD, Boston University School of Medicine.)
E-Fig. 31.2 Computed tomographic image of acute diverticulitis, with
evidence of diverticula and surrounding fat stranding. (Courtesy Jorge
Soto, MD, Boston University School of Medicine.)
E-Fig. 31.3 Computed tomographic image of acute pancreatitis, with
edema of the pancreas and surrounding fat stranding. (Courtesy Jorge
Soto, MD, Boston University School of Medicine.)
E-Fig. 31.4 Computed tomographic image of ulcerative colitis, with
inflammation and edema of the descending colon. (Courtesy Jorge
Soto, MD, Boston University School of Medicine.)
CHAPTER 31 Common Clinical Manifestations of Gastrointestinal Disease: Abdominal Pain
History and
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
physical examination
Structural studies
345
Abnormal
Cancer
Chronic
pancreatitis
Ischemia
IBD
Specific treatment
Success Failure
Continue Reevaluate
Fig. 31.1 Approach to the patient with chronic abdominal pain. IBD, Inflammatory bowel disease; IBS,
irritable bowel syndrome.
Depression
Tr ial of antidepressant
treatment
Acid suppression
Motility agents
tegaserod showed promise initially, they have been relegated to limited use due to unacceptable side effects. Eluxadoline, which targets
opioid receptors, has been helpful in some cases of IBS-D in controlling pain and diarrhea in patients who have failed loperamide.
Linaclotide causes increased secretion of chloride and bicarbonate
into the intestinal lumen via a cyclic guanosine monophosphate
(cGMP) pathway. This pathway also may be responsible for relief
of visceral pain in patients with IBS-C. However, its use has been
limited by unacceptable side effects, though a lower 72 mcg dose is
now available. A new member of this class, plecanatide, has shown
promise in initial studies but has not yet proved to be more effective than linaclotide. Tenapanor is a member of a new class of small
molecule medications that act by inhibiting transport of sodium
from the lumen of the large intestine, leading to improvements in
constipation and pain in patients with IBS-C. This medication is
still in the process of study but has been approved by the FDA. It
represents a new method of treatment.
The more challenging clinical problem is functional abdominal
pain syndrome. This term describes a condition in which the pain
has been present for months or years. The complaints of pain often
are not related to eating, defecation, or menses, unlike other causes
of chronic pain. The patient is most likely to be a woman who has
undergone numerous examinations and diagnostic studies with negative findings and, in many cases, surgical operations without any
relief. Lengthy or repeated diagnostic work-ups are counterproductive and only convince the patient that one more test is what is needed
to determine the source of the pain. The physician must establish that
organic disease is not present and must also realize that the pain is
real. These patients are not malingerers despite the fact that the pain
does not fit any familiar pattern. Depression may be the result rather
than the cause of the pain.
Management of chronic abdominal pain is demanding and requires
as much tact, diplomacy, and compassion as scientific knowledge. An
effort should be made to inquire about social factors, including history
Normal
ssol thgiew oNssol thgieW
Dyspepsia
IBS
Lifestyle changes
Anticholinergics
Fiber
Benign chronic
abdominal pain
Detailed social
history
Pain management
consultation
of physical and sexual abuse, particularly in women. Psychiatric evaluation may be necessary, but the suggestion for such a consultation may
be interpreted by the patient as evidence that the physician believes
“the pain is in my head.” Referral to a competent pain management
specialist is helpful in some cases. This approach offers the possibility
of providing relief with nerve blocks if the pain is localized or with
other pain-relieving devices. If this approach fails, referral to a psychologist or psychiatrist may be acceptable to the patient.
Because of the challenges involved with chronic pain treatment,
especially in light of the current issues with opioids, new approaches
using less traditional methods are being tried.
A new study done in the Netherlands showed that use of tetrahydrocannabinol, one of the active substances in marijuana, is not effective in the treatment of chronic pain from prior surgery or chronic
pancreatitis.
Fig. 31.1 presents a practical approach to chronic abdominal pain.
For further information, please see Chapter 128, “Functional
Gastrointestinal Disorders,” in Goldman-Cecil Medicine, 26th Edition.
SUGGESTED READINGS
Almario CV, Ballal ML, Chey WD, et al: Burden of gastrointestinal symptoms
in the United States: results of a nationally representative survey of over
71,000 Americans, Am J Gastroenterol 113:1701–1710, 2018.
Brenner DM, Fogel R, Dorn SD, et al: Efficacy, safety, and tolerability of
plecanatide in patients with irritable bowel syndrome with constipation:
results of two phase 3 randomized clinical trials, Am J Gastroenterol
113:735–745, 2018.
Brenner DM, Sayuk GS, Gutman CR, et al: Efficacy and safety of eluxadoline
in patients with irritable bowel syndrome with diarrhea who report
inadequate symptom control with loperamide: RELIEF phase 4 study, Am
J Gastroenterol 114:1502–1511, 2019.
Chang L, Lembo A, Sultan S: American gastroenterological association
institute technical review on the pharmacological management of irritable
bowel syndrome, Gastroenterology 147:1149–1172, 2014.
346 SECTION VI Gastrointestinal Disease
Chey WD, Lembo AJ, Rosenbaum DP: Tenapanor treatment of patients
with constipation-predominant irritable bowel syndrome: a phase
2, randomised, placebo-controlled efficacy and safety trial, Am J
Gastroenterol 112:763–774, 2017.
De Vries M, van Rijckevorsel DCM, Vissers KCP, et al: Tetrahydrocannabinol
does not reduce pain in patients with chronic abdominal pain in a phase 2
placebo-controlled study, Clin Gastroenterol Hepatol 15:1079–1086, 2017.
Lacy BE, Chey WD, Cash BD, et al: Eluxadoline efficacy in IBS-D patients who
report prior loperamide use, Am J Gastroenterol 112:924–932, 2017.
Schoenfeld P, Lacey BE, Chey WD, et al: Low dose linaclotide (72 μg) for
chronic idiopathic constipation: a 12-week, randomized, double-blind,
placebo-controlled trial, Am J Gastroenterol 113:105–114, 2017.
Shah ED, Kim HM, Shoenfeld P: Efficacy and tolerability of guanylate
cyclase-c agonists for irritable bowel syndrome with constipation and
chronic idiopathic constipation: a systematic review and meta-analysis,
Am J Gastroenterol 113:329–338, 2018.
Sperber AD, Drossman D: The functional abdominal pain syndrome, Aliment
Pharmacol Ther 33:514–524, 2011.
32
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Common Clinical Manifestations
of Gastrointestinal Disease:
Gastrointestinal Hemorrhage
Waihong Chung, Abbas Rupawala
INTRODUCTION
Gastrointestinal bleeding (GIB) is a major cause of morbidity,
accounting for over 844,000 emergency department visits and 513,000
hospitalizations in the United States in 2014. GIB also accounts for
over 2.2 million days of productivity loss and $5 billion in direct cost
annually. Despite increasing costs of care, mortality due to GIB has
declined in recent years in part due to increased rates of endoscopy
and improved endoscopic therapy. GIB can result from a variety of
etiologies (Table 32.1), its presentation can vary greatly depending on
age and comorbidity, and its clinical course can evolve rapidly over
time and in response to treatment. It is, therefore, essential to apply a
systematic approach to the management of all cases of suspected GIB.
We advocate a four-step approach that can be encapsulated by a simple
mnemonic PRET: Prioritize, Resuscitate, Evaluate, and Treat.
APPROACH TO PATIENTS WITH
GASTROINTESTINAL BLEEDING
Prioritize
The first step in the approach to GIB is to prioritize and triage patients
based on acuity and severity of blood loss. The objective of this step is
to guide the pace of evaluation and ensure that the patient is managed
in a timely and cost-effective manner.
GIB can be broadly classified as overt GIB, when patients present
with hematemesis, coffee-ground emesis, melena, or hematochezia (Table 32.2), and occult GIB, when symptoms of overt bleeding
are absent but patients are anemic with heme (occult blood) positive
stools. In addition to symptoms of bleeding, patients may also present
with some combination of weakness, dizziness, lightheadedness, shortness of breath, postural changes in blood pressure or pulse, cramping
abdominal pain, and diarrhea. Intuitively, overt GIB likely represents
faster or higher volume blood loss; thus, patients presenting with overt
GIB should be prioritized to receive an expedited work-up in the emergency room or in the inpatient setting. Meanwhile, patients with occult
GIB, who are otherwise asymptomatic, may be evaluated safely and
more efficiently in the outpatient setting.
GIB can also be classified into acute GIB, arbitrarily defined as
bleeding duration of less than 3 days, and chronic GIB. The authors,
however, find this classification less useful in guiding prioritization
because it fails to convey the difference in severity between protracted
or continual occult GIB versus ongoing or recurrent overt GIB.
Resuscitate
The second step is to resuscitate and stabilize the patient’s hemodynamic parameters and to alleviate symptoms. The objective of this step
is to prevent and reverse the complications of blood loss and restore
end-organ perfusion. It is worth emphasizing that adequate resuscitation is the most important step in the management of GIB and must
take priority over the subsequent steps of evaluation and treatment.
In cases of overt GIB, the resuscitative effort should follow the basic
principle of airway, breathing, and circulation. Airway management
and respiratory support should be considered in patients presenting
with massive or recurrent hematemesis as well as those with altered
mental status to minimize risk of aspiration. Restoration of normal
circulatory function should be achieved by rapid infusion of an isotonic crystalloid fluid, such as normal saline or lactated Ringer’s solution. Concerns regarding volume overload and pulmonary edema in
patients with heart failure or renal failure should not delay initiation of
fluid resuscitation but may necessitate the use of positive-pressure ventilation. A restrictive transfusion threshold of hemoglobin less than 7
g/dL has been shown to improve survival (95% vs. 91%) and decreased
rebleeding (10% vs. 16%) compared to a threshold of 9 g/dL. This is
especially true in cirrhotic patients presenting with suspected variceal
bleeding where over-transfusion may increase portal hypertension,
bleeding and mortality.
In cases of occult GIB, resuscitation should aim at relieving the
symptoms of anemia. Those with severe, symptomatic anemia and
signs of end-organ ischemia, such as angina or renal insufficiency,
may be transfused. Those with nonsevere symptoms of anemia, such
as weakness, fatigue, exercise intolerance, or exertional dyspnea, can
receive oral or parenteral iron replacement therapy.
Evaluate
The third step is performing a focused history and physical exam and
obtaining relevant laboratory and imaging tests (Table 32.3). The goal
of this step is to localize the potential bleeding site and identify the
most likely etiology of the bleed.
From a diagnostic and therapeutic perspective, it is most useful to
distinguish GIB into upper GIB (UGIB), historically defined as bleeding
emanating from a source proximal to the ligament of Treitz, and lower
GIB (LGIB). LGIB can be further subdivided into small bowel bleeding, originating proximal to the terminal ileum, and colonic bleeding.
UGIB has traditionally been considered to account for 76% to 82% of
GIB cases and is associated with a significantly higher emergency room
to hospital admission rate (78% vs. 40%) as well as in-hospital mortality (1.5% vs. 0.5%) compared to LGIB. Patients with suspected UGIB
should, therefore, be managed more aggressively, including offering
an early endoscopy within 24 hours of presentation, while those with
self-limiting LGIB may be observed clinically. Up to 15% of patients
presenting with presumed LGIB may have UGIB. The term obscure
347
Соседние файлы в папке Библиотека им академика М.И. Перельмана