Q.2. Obstructed jaundice is associated with all of the following except:
A. Elevated indirect serum bilirubinaemia.
B. Elevated direct serum bilirubinaemia.
C. Presence of bilirubinuria.
D. Urobilinogenuria is almost always present.
E. Raised alkaline phosphatase.
CBD stones should be suspected in any patient with cholecystitis
whose serum bilirubin level exceeds 85.5 _mol/L (5 mg/dL). The
maximum bilirubin level is seldom over 256.5 _mol/L (15.0 mg/dL)
in patients with choledocholithiasis unless concomitant hepatic disease
or another factor leading to marked hyperbilirubinemia exists. Serum
bilirubin levels of 342.0 _mol/L (20 mg/dL) or more should suggest
the possibility of neoplastic obstruction. The serum alkaline phosphatase
level is almost always elevated in biliary obstruction. A rise in
alkaline phosphatase often precedes clinical jaundice and may be the
only abnormality in routine liver function tests. There may be a twoto
tenfold elevation of serum aminotransferases, especially in association
with acute obstruction. Following relief of the obstructing process,
serum aminotransferase elevations usually return rapidly to normal,
while the serum bilirubin level may take 1 to 2 weeks to return
to normal. The alkaline phosphatase level usually falls slowly, lagging
behind the decrease in serum bilirubin
Acute cholecystitis: Leukocytosis and elevated LFTs with an obstructive picture (elevated alkaline phosphotase and bilirubin) are usually present
Q.1. A 30 years old man presented with generalized fatigue ability for 2 months. On examination he has found to have generalized lymph adenopathy. Differential diagnosis of this case includes all of the following except:
A. Lymphoma. T
B. HIV infection.
C. Hepatitis C virus infection.
D. Infectious mononucleosis.
E. Toxoplasmosis.
TABLE 54-1 Diseases Associated with Lymphadenopathy
1. Infectious diseases
a. Viral—infectious mononucleosis syndromes (EBV, CMV), infectious
hepatitis, herpes simplex, herpesvirus-6, varicella-zoster virus,
rubella, measles, adenovirus, HIV, epidemic keratoconjunctivitis,
vaccinia, herpesvirus-8
b. Bacterial—streptococci, staphylococci, cat-scratch disease, brucellosis,
tularemia, plague, chancroid, melioidosis, glanders, tuberculosis,
atypical mycobacterial infection, primary and secondary syphilis,
diphtheria, leprosy
c. Fungal—histoplasmosis, coccidioidomycosis, paracoccidioidomycosis
d. Chlamydial—lymphogranuloma venereum, trachoma
e. Parasitic—toxoplasmosis, leishmaniasis, trypanosomiasis, filariasis
f. Rickettsial—scrub typhus, rickettsialpox
2. Immunologic diseases
a. Rheumatoid arthritis
b. Juvenile rheumatoid arthritis
c. Mixed connective tissue disease
d. Systemic lupus erythematosus
e. Dermatomyositis
f. Sjo¨gren’s syndrome
g. Serum sickness
h. Drug hypersensitivity—diphenylhydantoin, hydralazine, allopurinol,
primidone, gold, carbamazepine, etc.
i. Angioimmunoblastic lymphadenopathy
j. Primary biliary cirrhosis
k. Graft-vs.-host disease
l. Silicone-associated
3. Malignant diseases
a. Hematologic—Hodgkin’s disease, non-Hodgkin’s lymphomas,
acute or chronic lymphocytic leukemia, hairy cell leukemia, malignant
histiocytosis, amyloidosis
b. Metastatic—from numerous primary sites
4. Lipid storage diseases—Gaucher’s, Niemann-Pick, Fabry, Tangier
5. Endocrine diseases—hyperthyroidism
6. Other disorders
a. Castleman’s disease (giant lymph node hyperplasia)
b. Sarcoidosis
c. Dermatopathic lymphadenitis
d. Lymphomatoid granulomatosis
e. Histiocytic necrotizing lymphadenitis (Kikuchi’s disease)
f. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman
disease)
g. Mucocutaneous lymph node syndrome (Kawasaki’s disease)
h. Histiocytosis X
i. Familial mediterranean fever
j. Severe hypertriglyceridemia
k. Vascular transformation of sinuses
l. Inflammatory pseudotumor of lymph node
Q.3. In rheumatoid arthritis all of the following are true except:
A. Causes destruction of articular cartilage.
B. Is frequently associated with the HLA antigen DR4.
C. Is equally common in males & females.
D. Is characterized by the presence of nodules.
E. Can involve any synovial joint in the body.
Rheumatoid arthritis (RA) is a chronic multisystem disease of unknown
cause. Although there are a variety of systemic manifestations,
the characteristic feature of RA is persistent inflammatory synovitis,
usually involving peripheral joints in a symmetric distribution. The
potential of the synovial inflammation to cause cartilage damage and
bone erosions and subsequent changes in joint integrity is the hallmark
of the disease. Despite its destructive potential, the course of RA can
be quite variable. Some patients may experience only a mild oligoarticular
illness of brief duration with minimal joint damage, whereas
others will have a relentless progressive polyarthritis with marked
functional impairment.
EPIDEMIOLOGY AND GENETICS The prevalence of RA is approximately
0.8% of the population (range 0.3 to 2.1%); women are affected approximately
three times more often than men. The prevalence increases
with age, and sex differences diminish in the older age group.
RA is seen throughout the world and affects all races. However, the
incidence and severity seem to be less in rural sub-Saharan Africa and
in Caribbean blacks. The onset is most frequent during the fourth and
fifth decades of life, with 80% of all patients developing the disease
between the ages of 35 and 50. The incidence of RA is more than six
times greater in 60- to 64-year-old women compared to 18- to 29-yearold
women. Recent data indicate that the incidence of RA may be
diminishing.
Family studies indicate a genetic predisposition. For example, severe
RA is found at approximately four times the expected rate in firstdegree
relatives of individuals with disease associated with the presence
of the autoantibody, rheumatoid factor; approximately 10% of
patients with RA will have an affected first-degree relative. Moreover,
monozygotic twins are at least four times more likely to be concordant
for RA than dizygotic twins, who have a similar risk of developing
RA as nontwin siblings. Only 15 to 20% of monozygotic twins are
concordant for RA, however, implying that factors other than genetics
play an important etiopathogenic role. Of note, the highest risk for
concordance of RA is noted in twins who have two HLA-DRB1 alleles
known to be associated with RA. The class II major histocompatibility
complex allele HLA-DR4 (DR_1*0401) and related alleles are known
to be major genetic risk factors for RA. Early studies showed that as
many as 70% of patients with classic or definite RA express HLADR4
compared with 28% of control individuals. An association with
HLA-DR4 has been noted in many populations, including North
American and European whites, Chippewa Indians, Japanese, and native
populations in India, Mexico, South America, and southern China.
In a number of groups, including Israeli Jews, Asian Indians, and Yakima
Indians of North America, however, there is no association between
the development of RA and HLA-DR4. In these individuals,
there is an association between RA and the closely related HLA-DR1
(DR_1*0101) in the former two groups and HLA-Dw16
(DR_1*1402) in the latter. It has been estimated that the risk of developing
RA in a person with DR_1*0401 or the closely related
DR_1*0404 is 1 in 35 and 1 in 20, respectively, whereas the presence
of both alleles puts persons at an even greater risk. In certain groups
of patients, there does not appear to be a clear association between
HLA-DR4–related epitopes and RA. Thus, nearly 75% of African-
American RA patients do not have this genetic element. Moreover,
there is an association with HLA-DR10 (DR_1*1001) in Spanish and
Italian patients, with HLA-DR9 (DR_1*0901) in Chileans, and with
HLA-DR3 (DR_1*0301) in Arab populations.
Additional genes in the HLA-D complex may also convey altered
susceptibility to RA. Certain HLA-DR alleles, including HLA-DR5
(DR_1*1101), HLA-DR2 (DR_1*1501), HLA-DR3 (DR_1*0301),
and HLA-DR7 (DR_1*0701), may protect against the development of
RA in that they tend to be found at lower frequency in RA patients
than in controls. Moreover, the HLA-DQ alleles, DQ_1*0301 and
DQ_1*0302, that are in linkage disequilibrium with HLA-DR4 and
DQ_1*0501, have also been associated with RA. This has raised the
possibility that HLA-DQ alleles may represent the actual RA susceptibility
genes, whereas specific HLA-DR alleles may convey protection.
In this model, the complement of HLA-DR and DQ alleles determines
RA susceptibility. Disease manifestations have also been
associated with HLA phenotype. Thus, early aggressive disease and
extraarticular manifestations are more frequent in patients with
DR_1*0401 or DR_1*0404, and more slowly progressive disease in
those with DR_1*0101. The presence of both DR_1*0401 and
DR_1*0404 appears to increase the risk for both aggressive articular
and extraarticular disease. It has been estimated that HLA genes contribute
only a portion of the genetic susceptibility to RA. Thus genes
outside the HLA complex also contribute. These include genes controlling
the expression of the antigen receptor on Tcells and both
immunoglobulin heavy and light chains. Moreover, polymorphisms in
the tumor necrosis factor (TNF) and the interleukin (IL) 10 genes are
also associated with RA, as is a region on chromosome 3 (3q13). In
addition, a number of other genetic regions appear to confer risk for
RA.
Genetic risk factors do not fully account for the incidence of RA,
suggesting that environmental factors also play a role in the etiology
of the disease. This is emphasized by epidemiologic studies in Africa
that have indicated that climate and urbanization have a major impact
on the incidence and severity of RA in groups of similar genetic background.
ETIOLOGY The cause of RA remains unknown. It has been suggested
that RA might be a manifestation of the response to an infectious agent
in a genetically susceptible host. Because of the worldwide distribution
of RA, it has been hypothesized that if an infectious agent is involved,
the organism must be ubiquitous. A number of possible causative
agents have been suggested, including Mycoplasma, Epstein-Barr virus
(EBV), cytomegalovirus, parvovirus, and rubella virus, but convincing
evidence that these or other infectious agents cause RA has
not emerged. The process by which an infectious agent might cause
chronic inflammatory arthritis with a characteristic distribution also
remains a matter of controversy. One possibility is that there is persistent
infection of articular structures or retention of microbial products
in the synovial tissues that generates a chronic inflammatory
response. Alternatively, the microorganism or response to the microorganism
might induce an immune response to components of the joint
by altering its integrity and revealing antigenic peptides. In this regard,
reactivity to type II collagen and heat shock proteins has been demonstrated.
Another possibility is that the infecting microorganism
might prime the host to cross-reactive determinants expressed within
the joint as a result of “molecular mimicry.” Recent evidence of similarity
between products of certain gram-negative bacteria and EBV
and the HLA-DR4 molecule itself has supported this possibility. Finally,
products of infecting microorganisms, such as superantigens,
might induce the disease. Superantigens are proteins with the capacity
to bind to HLA-DR molecules and particular V_ segments of the heterodimeric
Tcell receptor and stimulate specific T cells expressing the
V_ gene products (Chap. 295). The role of superantigens in the etiology
of RA remains speculative. Of all the potential environmental
triggers, the only one clearly associated with the development of RA
is cigarette smoking.
Signs and Symptoms of Articular Disease Pain, swelling, and tenderness
may initially be poorly localized to the joints. Pain in affected joints,
aggravated by movement, is the most common manifestation of established
RA. It corresponds in pattern to the joint involvement but does
not always correlate with the degree of apparent inflammation. Generalized
stiffness is frequent and is usually greatest after periods of
inactivity. Morning stiffness of greater than 1-h duration is an almost
invariable feature of inflammatory arthritis and may serve to distinguish
it from various noninflammatory joint disorders. Notably, however,
the presence of morning stiffness may not reliably distinguish
between chronic inflammatory and noninflammatory arthritides, as it
is also found frequently in the latter. The majority of patients will
experience constitutional symptoms such as weakness, easy fatigability,
anorexia, and weight loss. Although fever to 40_C occurs on occasion,
temperature elevation in excess of 38_C is unusual and suggests
the presence of an intercurrent problem such as infection.
Clinically, synovial inflammation causes swelling, tenderness, and
limitation of motion. Initially, impairment in physical function is
caused by pain and inflammation, and disability owing to this is a
frequent early feature of aggressive RA. Warmth is usually evident on
examination, especially of large joints such as
the knee, but erythema is infrequent. Pain originates
predominantly from the joint capsule,
which is abundantly supplied with pain fibers
and is markedly sensitive to stretching or distention.
Joint swelling results from accumulation
of synovial fluid, hypertrophy of the
synovium, and thickening of the joint capsule.
Initially, motion is limited by pain. The inflamed
joint is usually held in flexion to maximize
joint volume and minimize distention of
the capsule. Later, fibrous or bony ankylosis
or soft tissue contractures lead to fixed deformities.
Although inflammation can affect any diarthrodial
joint, RA most often causes symmetric
arthritis with characteristic involvement
of certain specific joints such as the
proximal interphalangeal and metacarpophalangeal
joints. The distal interphalangeal joints
are rarely involved. Synovitis of the wrist
joints is a nearly uniform feature of RA and
may lead to limitation of motion, deformity,
and median nerve entrapment (carpal tunnel
syndrome). Synovitis of the elbow joint often
leads to flexion contractures that may develop
early in the disease. The knee joint is commonly
involved with synovial hypertrophy,
chronic effusion, and frequently ligamentous
laxity. Pain and swelling behind the knee may be caused by extension
of inflamed synovium into the popliteal space (Baker’s cyst). Arthritis
in the forefoot, ankles, and subtalar joints can produce severe pain
with ambulation as well as a number of deformities. Axial involvement
is usually limited to the upper cervical spine. Involvement of the lumbar
spine is not seen, and lower back pain cannot be ascribed to rheumatoid
inflammation. On occasion, inflammation from the synovial
joints and bursae of the upper cervical spine leads to atlantoaxial subluxation.
This usually presents as pain in the occiput but on rare occasions
may lead to compression of the spinal cord.
With persistent inflammation, a variety of characteristic joint
changes develop. These can be attributed to a number of pathologic
events, including laxity of supporting soft tissue structures; damage or
weakening of ligaments, tendons, and the joint capsule; cartilage degradation;
muscle imbalance; and unopposed physical forces associated
with the use of affected joints. Characteristic changes of the hand
include (1) radial deviation at the wrist with ulnar deviation of the
digits, often with palmar subluxation of the proximal phalanges (“Z”
deformity); (2) hyperextension of the proximal interphalangeal joints,
with compensatory flexion of the distal interphalangeal joints (swanneck
deformity); (3) flexion contracture of the proximal interphalangeal
joints and extension of the distal interphalangeal joints (boutonnie`
re deformity); and (4) hyperextension of the first interphalangeal
joint and flexion of the first metacarpophalangeal joint with a consequent
loss of thumb mobility and pinch. Typical joint changes may
also develop in the feet, including eversion at the hindfoot (subtalar
joint), plantar subluxation of the metatarsal heads, widening of the
forefoot, hallux valgus, and lateral deviation and dorsal subluxation of
the toes. Later in the disease, disability is more related to structural
damage to articular structures.
Extraarticular Manifestations RA is a systemic disease with a variety of
extraarticular manifestations. Although these occur frequently, not all
of them have clinical significance. However, on occasion, they may
be the major evidence of disease activity and source of morbidity and
require management per se. As a rule, these manifestations occur in
individuals with high titers of autoantibodies to the Fc component of
immunoglobulin G (rheumatoid factors).
Rheumatoid nodules develop in 20 to 30% of persons with RA
They are usually found on periarticular structures, extensor surfaces,
or other areas subjected to mechanical pressure, but they can develop
elsewhere, including the pleura and meninges. Common locations include
the olecranon bursa, the proximal ulna, the Achilles tendon, and
the occiput. Nodules vary in size and consistency and are rarely symptomatic,
but on occasion they break down as a result of trauma or
become infected. They are found almost invariably in individuals with
circulating rheumatoid factor. Histologically, rheumatoid nodules consist
of a central zone of necrotic material including collagen fibrils,
noncollagenous filaments, and cellular debris; a midzone of palisading
macrophages that express HLA-DR antigens; and an outer zone of
granulation tissue. Examination of early nodules has suggested that
the initial event may be a focal vasculitis. In some patients, treatment
with methotrexate can increase the number of nodules dramatically.
Clinical weakness and atrophy of skeletal muscle are common.
Muscle atrophy may be evident within weeks of the onset of RA and
is usually most apparent in musculature approximating affected joints.
Muscle biopsy may show type II fiber atrophy and muscle fiber necrosis
with or without a mononuclear cell infiltrate.
Q.4. Which of the following indicate pre-renal failure:
A. Cast in the urine.
B. Low urine osmolality [< 400 mosmmol/kg]
C. Low urine sodium concentration [< 20mmol/L]
D. Low free water excretion.
E. Microscopic hematuria.
Acute renal failure (ARF) is a syndrome characterized by rapid decline
in glomerular filtration rate (hours to days), retention of nitrogenous
waste products, and perturbation of extracellular fluid volume and
electrolyte and acid-base homeostasis. ARF complicates approximately
5% of hospital admissions and up to 30% of admissions to
intensive care units. Oliguria (urine output _ 400 mL/d) is a frequent
but not invariable clinical feature (_50%). ARF is usually asymptomatic
and diagnosed when biochemical monitoring of hospitalized patients
reveals a recent increase in blood urea and creatinine
concentrations. It may complicate a wide range of diseases, which for
purposes of diagnosis and management are conveniently divided into
three categories: (1) diseases that cause renal hypoperfusion without
compromising the integrity of renal parenchyma (prerenal ARF, prerenal
azotemia) (_55%); (2) diseases that directly involve renal parenchyma
(intrinsic renal ARF, renal azotemia) (_40%); and (3)
diseases associated with urinary tract obstruction (postrenal ARF,
postrenal azotemia) (_5%). Most ARF is reversible, the kidney being
relatively unique among major organs in its ability to recover from
almost complete loss of function. Nevertheless, ARF is associated with
major in-hospital morbidity and mortality, in large part due to the
serious nature of the illnesses that precipitate the ARF.
ETIOLOGY AND PATHOPHYSIOLOGY
PRERENAL ARF (PRERENAL AZOTEMIA) Prerenal ARF is the most common
form of ARF and represents a physiologic response to mild to moderate
renal hypoperfusion. Prerenal ARF is by definition rapidly reversible
upon restoration of renal blood flow and glomerular
ultrafiltration pressure. Renal parenchymal tissue is not damaged; indeed,
kidneys from individuals with prerenal ARF function well when
transplanted into recipients with normal cardiovascular function. More
severe hypoperfusion may lead to ischemic injury of renal parenchyma
and intrinsic renal ARF (see below). Thus, prerenal ARF and intrinsic
renal ARF due to ischemia are part of a spectrum of manifestations of
renal hypoperfusion. As shown in Table 260-1, prerenal ARF can complicate
any disease that induces hypovolemia, low cardiac output, systemic
vasodilatation, or selective intrarenal vasoconstriction.
Hypovolemia leads to a fall in mean systemic arterial pressure,
which is detected as reduced stretch by arterial (e.g., carotid sinus)
and cardiac baroreceptors. Activated baroreceptors trigger a coordinated
series of neural and humoral responses designed to restore blood
volume and arterial pressure. These include activation of the sympathetic
nervous system and renin-angiotensin-aldosterone system and
release of arginine vasopressin (AVP; formerly called antidiuretic hormone).
Norepinephrine, angiotensin II, and AVP act in concert in an
attempt to preserve cardiac and cerebral perfusion by stimulating vasoconstriction
in relatively “nonessential” vascular beds, such as the
musculocutaneous and splanchnic circulations, by inhibiting salt loss
through sweat glands, by stimulating thirst and salt appetite, and by
promoting renal salt and water retention. Glomerular perfusion, ultrafiltration
pressure, and filtration rate are preserved during mild hypoperfusion
through several compensatory mechanisms. Stretch
receptors in afferent arterioles, in response to a reduction in perfusion
pressure, trigger afferent arteriolar vasodilatation through a local myogenic
reflex (autoregulation). Biosynthesis of vasodilator prostaglandins
(e.g., prostaglandin E2 and prostacyclin) is also enhanced, and
these compounds preferentially dilate afferent arterioles. In addition,
angiotensin II induces preferential constriction of efferent arterioles.
As a result, intraglomerular pressure is maintained, the fraction of
plasma flowing through glomerular capillaries that is filtered is increased
(filtration fraction), and glomerular filtration rate (GFR) is preserved.
During states of more severe hypoperfusion, these
compensatory responses are overwhelmed and GFR falls, leading to
prerenal ARF.
Autoregulatory dilatation of afferent arterioles is maximal at mean
systemic arterial blood pressures of _80 mmHg, and hypotension below
this level is associated with a precipitous decline in GFR. Lesser
degrees of hypotension may provoke prerenal ARF in the elderly and
in patients with diseases affecting the integrity of afferent arterioles
(e.g., hypertensive nephrosclerosis, diabetic vasculopathy). In addition,
drugs that interfere with adaptive responses in the renal microcirculation
may convert compensated renal hypoperfusion into overt
prerenal ARF or trigger progression of prerenal ARF to ischemic intrinsic
renal ARF (see below). Pharmacologic inhibitors of either renal
prostaglandin biosynthesis [cyclooxygenase inhibitors; nonsteroidal
anti-inflammatory drugs (NSAIDs)] or angiotensin-converting enzyme
(ACE) activity (ACE inhibitors) and angiotensin II receptor blockers
are the major culprits and should be used judiciously in the setting of
suspected renal hypoperfusion. NSAIDs do not compromise GFR in
healthy individuals but may precipitate prerenal ARF in patients with
volume depletion or in those with chronic renal insufficiency in whom
GFR is maintained, in part, through prostaglandin-mediated hyperfiltration
by the remaining functional nephrons. ACE inhibitors should
be used with special care in patients with bilateral renal artery stenosis
or unilateral stenosis in a solitary functioning kidney. In these settings
glomerular perfusion and filtration may be exquisitely dependent on
the actions of angiotensin II. Angiotensin II preserves glomerular filtration
pressure distal to stenoses by elevating systemic arterial pressure
and by triggering selective constriction of efferent arterioles.ACE
inhibitors blunt these responses and precipitate ARF, usually reversible,
in _30% of these patients.
Hepatorenal Syndrome This is a particularly aggressive form of ARF,
with many of the features of prerenal ARF, that frequently complicates
hepatic failure due to advanced cirrhosis or other liver diseases, including
malignancy, hepatic resection, and biliary obstruction. In fullblown
hepatorenal syndrome, ARF progresses even after optimization
TABLE 260-1 Classification and Major Causes of Acute Renal Failure (ARF)
PRERENAL ARF
I. Hypovolemia
A. Hemorrhage, burns, dehydration
B. Gastrointestinal fluid loss: vomiting, surgical drainage, diarrhea
C. Renal fluid loss: diuretics, osmotic diuresis (e.g., diabetes mellitus),
hypoadrenalism
D. Sequestration in extravascular space: pancreatitis, peritonitis,
trauma, burns, severe hypoalbuminemia
II. Low cardiac output
A. Diseases of myocardium, valves, and pericardium; arrhythmias;
tamponade
B. Other: pulmonary hypertension, massive pulmonary embolus, positive
pressure mechanical ventilation
III. Altered renal systemic vascular resistance ratio
A. Systemic vasodilatation: sepsis, antihypertensives, afterload reducers,
anesthesia, anaphylaxis
B. Renal vasoconstriction: hypercalcemia, norepinephrine, epinephrine,
cyclosporine, tacrolimus, amphotericin B
C. Cirrhosis with ascites (hepatorenal syndrome)
IV. Renal hypoperfusion with impairment of renal autoregulatory responses
Cyclooxygenase inhibitors, angiotensin-converting enzyme inhibitors
V. Hyperviscosity syndrome (rare)
Multiple myeloma, macroglobulinemia, polycythemia
INTRINSIC RENAL ARF
I. Renovascular obstruction (bilateral or unilateral in the setting of one
functioning kidney)
A. Renal artery obstruction: atherosclerotic plaque, thrombosis, embolism,
dissecting aneurysm, vasculitis
B. Renal vein obstruction: thrombosis, compression
II. Disease of glomeruli or renal microvasculature
A. Glomerulonephritis and vasculitis
B. Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura,
disseminated intravascular coagulation, toxemia of pregnancy,
accelerated hypertension, radiation nephritis, systemic lupus
erythematosus, scleroderma
III. Acute tubular necrosis
A. Ischemia: as for prerenal ARF (hypovolemia, low cardiac output,
renal vasoconstriction, systemic vasodilatation), obstetric complications
(abruptio placentae, postpartum hemorrhage)
B. Toxins
1. Exogenous: radiocontrast, cyclosporine, antibiotics (e.g., aminoglycosides),
chemotherapy (e.g., cisplatin), organic solvents
(e.g., ethylene glycol), acetaminophen, illegal abortifacients
2. Endogenous: rhabdomyolysis, hemolysis, uric acid, oxalate,
plasma cell dyscrasia (e.g., myeloma)
IV. Interstitial nephritis
A. Allergic: antibiotics (e.g., _-lactams, sulfonamides, trimethoprim,
rifampicin), nonsteroidal anti-inflammatory agents, diuretics, captopril
B. Infection: bacterial (e.g., acute pyelonephritis, leptospirosis), viral
(e.g., cytomegalovirus), fungal (e.g., candidiasis)
C. Infiltration: lymphoma, leukemia, sarcoidosis
D. Idiopathic
V. Intratubular deposition and obstruction
Myeloma proteins, uric acid, oxalate, acyclovir, methotrexate, sulphonamides
VI. Renal allograft rejection
POSTRENAL ARF (OBSTRUCTION)
I. Ureteric
Calculi, blood clot, sloughed papillae, cancer, external compression
(e.g., retroperitoneal fibrosis)
II. Bladder neck
Neurogenic bladder, prostatic hypertrophy, calculi, cancer, blood clot
III. Urethra
Stricture, congenital valve, phimosis
of systemic hemodynamics and carries a mortality rate of _90%.
The diagnosis and management of this condition are discussed in
Chaps. 289 and 291.
HEPATORENAL SYNDROME Definition and Pathogenesis Hepatorenal syndrome
is a serious complication in the patient with cirrhosis and ascites
and is characterized by worsening azotemia with avid sodium retention
and oliguria in the absence of identifiable specific causes of renal dysfunction.
The exact basis for this syndrome is not clear, but altered
renal hemodynamics appear to be involved. There is evidence for inappropriate
intense renal vasoconstriction, perhaps in response to the
splanchnic vasodilation accompanying cirrhosis. The kidneys are
structurally intact; urinalysis and pyelography are usually normal. Renal
biopsy, although rarely needed, is also normal, and in fact, kidneys
from such patients have been used successfully for renal transplantation.
Clinical Features and Diagnosis Worsening azotemia, hyponatremia, progressive
oliguria, and hypotension are the hallmarks of the hepatorenal
syndrome. This syndrome, which is distinct from prerenal azotemia,
may be precipitated by severe gastrointestinal bleeding, sepsis, or
overly vigorous attempts at diuresis or paracentesis; it may also occur
without an obvious cause. It is essential to exclude other causes of
renal impairment often seen in these patients. These include prerenal
azotemia or acute tubular necrosis due to hypovolemia (e.g., secondary
to gastrointestinal bleeding or diuretic therapy) or an increased nitrogen
load such as that seen as a result of bleeding. Drug nephrotoxicity
is also often a consideration, particularly in the patient who has received
agents such as aminoglycosides or contrast dye. The diagnosis
rests on the finding of an elevated serum creatinine level [_133_mol/
L (_1.5 g/dL)] that fails to improve with volume expansion or withdrawal
of diuretics, together with an unremarkable urine sediment. The
diagnosis is supported by the demonstration of avid urinary sodium
retention. Typically, the urine sodium concentration is _5 mmol/L, a
concentration lower than that generally found in uncomplicated pre
prerenal azotemia.
Treatment is usually unsuccessful. Although some patients with hypotension
and decreased plasma volume may respond to infusions of
salt-poor albumin, volume expansion must be undertaken with caution
to avoid precipitating variceal bleeding. Vasodilator therapy, including
intravenous infusions of low dose dopamine, is not effective. Evidence
for the benefit of systemic vasoconstrictors alone or in combination
with other agents such as terlipressin, norepinephrine with albumin,
and octreotide with midodrine has emerged recently, but additional
study is needed. While TIPS has been reported to improve renal function
in some patients, its use cannot be recommended. In appropriate
candidates, the treatment of choice for hepatorenal syndrome is liver
transplantation. In patients with spontaneous bacterial peritonitis, early
intravenous albumin infusion can prevent development of hepatorenal
syndrome in some patients.
Q.5. Hyponatremia occurs in the following conditions except:
A. Primary adrenocortical insufficiency.
B. Congestive heart failure.
C. Diabetic ketoacidosis with very high blood sugar.
D. Excessive production of vasopressin.
E. Diabetic insipidus.
TABLE 41-2 Causes of Hyponatremia
I. Pseudohyponatremia
A. Normal plasma osmolality
1. Hyperlipidemia
2. Hyperproteinemia
3. Posttransurethral resection of prostate/bladder tumor
B. Increased plasma osmolality
1. Hyperglycemia
2. Mannitol
II. Hypoosmolal hyponatremia
A. Primary Na_ loss (secondary water gain)
1. Integumentary loss: sweating, burns
2. Gastrointestinal loss: vomiting, tube drainage, fistula, obstruction,
diarrhea
3. Renal loss: diuretics, osmotic diuresis, hypoaldosteronism, saltwasting
nephropathy, postobstructive diuresis, nonoliguric acute
tubular necrosis
B. Primary water gain (secondary Na_ loss)
1. Primary polydipsia
2. Decreased solute intake (e.g., beer potomania)
3. AVP release due to pain, nausea, drugs
4. Syndrome of inappropriate AVP secretion
5. Glucocorticoid deficiency
6. Hypothyroidism
7. Chronic renal insufficiency
C. Primary Na_ gain (exceeded by secondary water gain)
1. Heart failure
2. Hepatic cirrhosis
3. Nephrotic syndrome
Q.9. Which of the following is a usual feature of interstitial lung disease like fibrosing alveolitis:
A. Fever.
B. Hemolysis.
C. Generalized wheezes.
D. Purulent sputum.
E. Fine crepitations
