Ebook Pathophysiology of disease flashcards - 120 case based flashcard with Q&A: Part 2

(BQ) Part 2 book Pathophysiology of disease flashcards - 120 case based flashcard with Q&A presents the following contents: Disorders of the adrenal medulla, gastrointestinal disease, renal disease, liver disease, disorders of the exocrine pancreas, disorders of the endocrine pancreas, thyroid disease, disorders of the adrenal cortex,...

61 Pheochromocytoma, A

A 39-year-old woman comes to the offiffi ce complaining

of episodic anxiety, headache, and palpitations Without

dieting, she has lost 15 pounds over the past 6 months

Physical examination is normal except for a blood pressure

of 200/100 mm Hg and a resting pulse rate of 110 bpm Chart review shows that prior blood pressures have alwaysbeen normal, including one 6 months ago A pheochromo-cytoma diagnosis is entertained

1 Which catecholamines are secreted by the human adrenal medulla?

Of these, which is the major product?

2 What genetic mutations are found in patients with pheochromocytoma?

•

Th e adrenal medulla s

ecretes epinephr

norepinephrine, an

d dopamine

•

Most (80%) o

f t

he catecholamine outp

a is epinephrine

•

10 kno

wn susceptibility genes a

re associated with

familial pheo

chromocyto

ma and/or paraganglio

ma

Examples include:

—Neurofibromatosis type 1 (Rec

klinghausen diseas

NF1

gene mutations

—Von Hippel–Lindau syndrome:

VHL

tum

or

suppresso

r gene mutation

—Multip

le endocrine neoplasia typ

e 2 (MEN-2):

missense poin

t mutation

nd most familial cases o

f

familia

l pheochromocyto

ma and/o

r paragangl

ioma

carr

y germline muta

tion

s in

VHL, RE

T, NF1 , SDH

A,

SDHB , SDH

C, SDH

D, S DH AF2, T MEM127, o

rMA

X.

Somatic mutation

•

Hypertensi

ve retinopath

y (retinal hemorr

hages or

papilledema)

•

Nephropathy

•

Myocardia

l infarctio

n resultin

g fro

m eith

er

catecholamine-ind

uced myocarditis and/or dilated

cardiomyopath

y o

r coronary artery vasospasm a

nd

cardiovascula

r collapse (sometimes fatal)

•

Pulmonary edema, seco

ndary eith

er to left -sided hear

t ft

failur

e or noncardiogenic causes

•

Strok

e fr

om cerebral infarctio

n, intracranial

hemorrhage,

or embolism fro

m mural thromb

i in

dilated cardiomyopathy

•

Ileus, obstipatio

n, an

d abdominal discomfor

t resulti

ng

from

a large adrena

l mass

•

Matern

al morbidity an

d fet

al demis

e in pregna

ncy

•

Increased blood suga

r levels, even diabet

es mellitu

s

•

Increased blood lactat

e concentrations

•

W eigh

t loss (o

r, in childr

en, lack o

f weig

•

Mild basal bod

y temperatu

re elevatio

n, heat i

•

Marked anxiety, visual

disturbances, paresth

esias, or

seizur

es an

d psychosis o

r confusio

n durin

productio

n of PTH-related peptid

me (ectopic

productio

n of ACTH)

3 What are some complications of untreated pheochromocytoma?

62 Achalasia, A

A 60-year-old man presents to the clinic with a 3-month

history of gradually worsening dysphagia (diffiffi culty

swal-lowing) At first, he noticed the problem when eating solidfi

food such as steak, but now it happens even with

drink-ing water He has a sensation that whatever he swallows

becomes stuck in his chest and does not go into the

stom-ach He has also developed worsening heartburn, especially

upon lying down, and has had to prop himself up at night

to lessen the heartburn He has lost 10 kg as a result of his swallowing diffi culties His physical examination is unre-ffimarkable A barium swallow x-ray reveals a decrease inperistalsis of the body of the esophagus along with dilata-tion of the lower esophagus and tight closure of the lower esophageal sphincter There is a beaked appearance of theThdistal esophagus involving the lower esophageal sphincter

Th ere is very little passage of barium into the stomach.Th

1 What is the role of the lower esophageal sphincter structure in achalasia?

•

Achalasia is a conditi

on where t

he lower esophage

al

sphincter fails to relax

•

Th e lower esophageal sphincter is a 3–4 cm r

in

g o

smooth musc

le that

is usuall

y contracted, und

er

stimulatio

n b

y vagal cholinergic inputs

•

Wh

en a swallow is initiate

d, vagal inhibito

ry fibers allo

w fi

the sphincter t

o relax s

o that th

e bolu

s of foo

d ca

n pass

in

to t

he stomach

•

In achalasia, ther

e is degeneration o

f t

he myen

•

Therefore, th

e sphincter remains tightl

y c

•

The neural dysfunc

tio

n ca

n also extend fu

rther u

p t

esophagus as well

, an

d eff ecti

ve esophageal peristal

sis ff ff

is als

o o

ft en lost ft

f esophage

al

achalasia is unknown

•

Degeneratio

n of t

he myenter

ic plexus a

nd loss o

f

inhibito

ry neuron

s th

at release vasointestina

l peptide

(VIP) a

nd nitric oxide, which dila

te t

he lower

esophage

al sphincter, ma

y contribute

•

Esophagea

l involvemen

t in Chagas disea

se, resulti

ng

from damag

e to th

e neural plexus

es of t

he esophagus

by t

he parasite

Trypa noso ma cruz

•

A numb

er of other disorder

e charac

ter

istics

or radiographic features simila

r to those observ

ed in

idiopathic esophage

al achalasia

2 What are possible causes of achalasia?

63 Refl ux Esophagitis, A

A 32-year-old woman presents to her primary care

pro-vider complaining of a persistent burning sensation in

her chest and upper abdomen The symptoms are worse Th

at night while she is lying down and after meals She has ft

tried drinking hot cocoa to help her sleep She is a smoker and frequently relies on benzodiazepines for insomnia Shenotes a sour taste in her mouth every morning Physicalexamination is normal

1 What is the role of the lower esophageal sphincter structure in refl ux esophagitis? fl

•

Normally, t

he lower esophage

al sphincter is tonicall

y

contracted, preventin

g th

e refl

ux of acid fro

m t

stomach back into th

e esophagus

•

Th is is reinfo

rced b

y secondary esophageal peristal

wav

es in respon

se t

o transien

t low

er esophageal

sphincter relaxations

•

Effectiveness of tha

t barrier can b

e alter

ed b

y loss o

lower esophage

al sphincter tone (ie, th

e opposi

te o

f

achalasia), increas

ed frequency o

f transien

t relaxations,

loss of secondary peristalsis aft

er transient relaxation

increased stomach volu

me or pressur

e, or increas

ed

productio

n of aci

d, a

ll o

f whic

ach conten

ts suffi fl cien

t to

caus

e pain ffi

or erosion

•

Recurren

t reflux ca

tis” fl

•

Recurre

nt reflux itse

lf predisposes t

o further refl fl

ux

because t

he scarrin

g that occurs with healin

s th

e low

er esophag

sphincter progressive

ly less competen

t as a barri

er

•

Occasionall

y, refl

ux esophagitis is caus

ed by alkaline fl

injury (eg, pancreatic juice refl

uxing through both

incompeten

t pyloric sphincter a

nd a relaxed lower

esophagea

l sphincter)

•

Hiat

al hernia, a disord

er in which

a portio

n of t

he

proximal sto

mac

h slides into th

e chest cavi

ty wi

th

upward displacemen

t of t

he lower esophage

al sphinc

ter

,

can contribute to th

e developmen

t of refl

ux

3 What are some other possible causes of refl ux esophagitis? fl

•

Chronic recurrent refl

ux can als

o resul

t in a chan

in t

he esophage

al epithelium fro

m a squamous to

columna

r histolo

gy (resemblin

g that

of t

he stomach

and/o

r intestine)

•

T ermed Barret

t esophagus, th

e disord

er is more

common in men a

nd in smoker

s, a

nd i

t leads to

a

greatl

y increas

ed risk o

f adenocarcinoma

•

Adenocarcinomas in th

e distal esophagus an

d p

ro

ximal

(cardiac) stom

ach related t

o Barrett esophagus a

re

among t

he most rapidl

y increasin

g typ

es of ca

ncer in

young, ma

le patients in t

he United States

2 What is the relationship of esophageal refl ux to Barrett esophagus and cancer? fl

64 Acid-Peptic Disease, A

A 74-year-old man with severe osteoarthritis presents

to the emergency department reporting two episodes of

melena (black stools) without hematochezia (bright red

blood in the stools) or hematemesis (bloody vomitus) He

takes 600 mg of ibuprofen three times a day to control his

arthritis pain He denies alcohol use On examination, his

blood pressure is 150/70 mm Hg and his resting pulse is 96/min His epigastrium is minimally tender to palpation.Rectal examination reveals black tarry stool in the vault, grossly positive for occult blood Endoscopy demonstrates

a 3 cm gastric ulcer Helicobacter pylori is identified onfibiopsies of the ulcer site

1 How might motility defects contribute to gastric ulcer?

•

Motilit

y defec

ts have been proposed

to contribu

te t

o

development o

f gastric ulcer in a

t least three ways:

—A tendenc

y of duodenal con

ten

ts to refl

ux bac

k fl

through a

n incompeten

t pyloric sphincter (bile acids

in th

e duodenal refl

ux material ac

t as an irritan

nt contributor to

a diminished

stomac

h mucos

al barrier)

—Delayed emptyin

g of gastr

ic conten

ts, includin

g

refl

ux material, into th

e duoden

—Delayed gastric emptyin

g an

d hence foo

g in increas

ed gastrin secretion a

nd

gastr

ic

acid production

•

It is no

t known whether thes

e motilit

y defec

ts are a

caus

e or a consequence of

gastr

ic ulcer form

atio

n

•

Of patien

ts wh

o do develop acid-peptic disease,

especially amon

g thos

e with duodenal ulcer

s, th

e vast

majorit

y have

H py lor

i in

fection

•

Treatmen

t th

at does no

t eradicate

H pyl ori

is associated

wit

h rap

id recurrence of acid-peptic disea

se in most

patients

•

Th er

e are numerous strains o

H pylo

ri t

hat vary in

their production o

f toxin

s such

as CagA and

V acA that

directl

y alt

er cellula

r signalin

g pathways

•

As man

y as 90% o

f infecte

d individuals show si

gns

of

infl ammatio

n (gastritis o

r duodenitis) o

n endos

cop

although man

y o

f thes

e individuals a

re clinica

lly

asymptomatic

•

Despite this hig

h rate

of associatio

n o

f inflamm

atio

n fl

with

H pylo ri

infection, t

he importa

nt role o

f o

ther

facto

rs is indicated b

y th

e fac

t th

at only abo

ut 15%

of infected individuals ever develop

a clinica

lly

signifi ca

nt ulcer fi

3 What evidence indicates the importance of H pylori infection in acid-peptic disease? i

•

NSAID

s may predispos

e to ulcer formation b

y

attenuating t

he barrier created b

y th

e epithelial cells and

the bicarbonat

e or mucu

s th

ey secrete

•

NSAIDs also reduce th

e quantity o

f prostagl

and

ins t

he

epithelial cells produce that migh

t otherwis

e d

iminish

acid secretion

2 How do NSAIDs contribute to acid-peptic disease?

65 Gastroparesis, A

A 67-year-old man with type 2 diabetes mellitus is seen by

his primary care provider for frequent nausea, bloating, and

intermittent diarrhea over the preceding 2 weeks The vom-Th

iting typically occurs approximately 1–2 hours after eating.ft

He states that over the past year, he has become increasingly

depressed after the death of his wife and has been less ftadherent to his oral hypoglycemic regimen and evening insulin He also reports 6 months of worsening neuropathicpain in his feet His fasting fingerstick blood glucose level isfi

253 mg/dL, and his hemoglobin A1C is 10.5%

1 What are the symptoms of delayed versus rapid gastric emptying?

•

Delayed gastr

ic emptyin

g causes sympto

ms o

f stomach

distensio

n, naus

ea, earl

y satiety, an

d vomiting

•

However, in so

me cases, delayed emptying ca

n resu

lt in

sympto

ms expecte

d fro

m excessive

ly rapid emptying

—A

n excessivel

y contracted pyloru

s th

at ca

n open

completel

y b

ut that does s

o infrequentl

y ca

n result

in entry into th

e duoden

um of t

oo large a b

olu

s of

chyme fro

m th

e excessivel

y distended

stom

ach

—Such a bolu

s may no

t be efficientl

y handl

g in poo

r abso

rp

tion a

nd

diarrhe

al sympto

ms characteristic o

•

Hormones play an ill-defined b

ut importa

nt role in fi

regulatio

n of GI motility

in health an

d disease

•

Erythromycin binds t

o a

nd inhibits t

he activation o

f

th

e recepto

r fo

r th

e GI hormon

e motilin, a

ff ectin

g GI ff ff

motility

•

So

me patien

ts with gastroparesis are obse

vemen

t with erythro

mycin a

nd

its analo

gs, especially w

hen complain

ts related t

o pa

rtial

gastric outl

et obstructio

n, such

as bloatin

g, naus

ea, a

nd

constipati

on, a

re prominent

3 Why might erythromycin improve diabetic gastroparesis?

•

Development o

f bezoa

rs fro

m retained gastr

ic contents

•

Bacterial overgrowth fro

m stasis of food

•

Erratic blood glucose control

•

W eigh

t loss when nausea an

d vomitin

g are profoun

d

•

Elevat

ed blood glucose ca

n be eith

er a caus

e or a

consequence of

delayed gastric emptying

•

Bacteria

l overgrowth itse

lf ca

n resu

lt in bot

h

malabsorption an

d diarrhea

2 What are the complications of gastroparesis?

66 Cholelithiasis and Cholecystitis, A

A 40-year-old woman presents to the emergency

depart-ment with 2 days of worsening right upper quadrant pain

Th e pain started aft

Th ft er she had pizza for dinner 2 nights

before and is described as a sharp, stabbing sensation under

her right ribs She has also felt ill, developed slight nausea,

and had a low-grade fever There has been no vomiting orTh

diarrhea Physical examination reveals an obese woman with a low-grade fever and tenderness to palpation of the right upper quadrant of her abdomen An abdominal ultra-sound reveals a 2 cm gallstone lodged in the cystic duct with swelling of the gallbladder and edema and thickening

of the gallbladder wall

1 What are the mechanisms involved in gallstone formation?

•

Factors affectin

g th

e lithogenici

ty of bile: ff ff

—Cholester

ol content

—Nucleatin

g factors

—Prostaglandins a

nd estrogen

—Rate

of bil

e formation

—Rate

of water a

nd electrolyt

e absorption

•

Gallbladder motility

is also importa

nt since bile usuall

ng enough

to f

orm a

gallstone; stasis allows ston

e formation

•

A gallston

e may become lodge

d in t

he cystic duc

t,

obstructin

g t

he emptying of th

e gallbladder

•

Th is ca

n lead t

o infl Th am

matio

n (cholecystitis) a

infection o

f t

he static conten

ts (empyema) o

f t

he

gallbladder

•

If untreated, suc

h infl ammatio

n an

d infection ca

n lead fl

to necrosis of t

he gallbladder an

d sepsis

•

If a gallston

e becomes lod

ged in t

he common bile duct,

it ca

n caus

e obstructive jaundice with elevation in serum

bilirubin levels and cholangitis, infection o

e obstruction

•

If lodged a

t t

he dist

al commo

n bile duct blo

ckin

g

th

e pancreat

ic duct ne

ar t

he sphincter o

f O

ddi,

a

gallsto

ne ca

n caus

e acu

te pancreatitis, perh

ve enzymes a

re trapp

ed in th

e

pancreatic duct an

d caus

e pancreatic auto

digestio

n

an

d inflammatio

s of serum estrogen

s increa

se cholesterol

concentratio

n o

f bile

•

High estrog

en levels also decrea

se gallbladder mo

tilit

y,

leadin

g to stasis

2 What factors in the pathogenesis of gallstones may be responsible for the fact that it is more common in premenopausal women?

67 Diarrhea, Non-Infectious, A

A 45-year-old man comes to the clinic with a history of

excessive bloating, foul smelling flatus, and loose stools for fl

the past several months He notes that about 30–60

min-utes aft er breakfast each morning, he feels cramping, bloat-ft

ing, passage of smelly fl atus, and a very loose, watery bowel fl

movement He has not seen any blood or mucus in the

stool and also denies any weight loss This does not happen Th

with lunch or dinner Every day for breakfast, he eats a big bowl of cereal with milk and a yogurt smoothie Physicalexamination is unremarkable with normal bowel sounds,

no organomegaly, and no abdominal tenderness He wasadvised to do a dietary trial of stopping dairy intake for

1 week All his symptoms resolve, and he is diagnosed withlactose intolerance

1 Name three ways in which an excessive osmotic load can occur in the GI tract.

•

Direct oral ingestion o

f excessive osmoles suc

h as

sorbitol

•

By ingestio

n of a substra

te that may b

e converted

in

to excessive osmoles (ie, bacteria

l action o

n t

he

digestibl

non-e carbohydrate lactulos

e generates a

diarrhea-causin

g osmotic load in t

he colon)

•

As a manifestatio

n of a genetic diseas

g of a partic

ular diet fi

(ie, milk consum

ptio

n by a lactase-deficien

t individ

ual) fi

•

Disaccharidase defi ciencies (ie, lacta

se defi ficiency) fi

•

Glucose-galacto

se o

r fructos

e malabsorption

•

Mannito

l, sorbito

l ingestion

•

Lactulos

e therapy

•

So

me sal

ts (ie, magnesi

um sulfate)

•

So

me antacids (ie, calcium carbonate)

•

Generalized malabso

rption

•

Pancreatic enzyme inactiva

tion (ie, by excess acid)

or deficiency fi

•

Defecti

ve fat solubilizatio

n (disrupte

d enter

oh

epatic

circulatio

n or defecti

ve bile formation)

•

Ingestio

n of nutrient-binding substances

•

Bacterial overgrowth

•

Lo

ss of enterocytes (ie, radiatio

n, infection, is

ch

emia)

•

Lymphatic obstruc

tio

n (ie, lympho

ma, tuber

culosis)

2 What are the major causes of osmotic/malabsorptive diarrhea?

68 Infl ammatory Bowel Disease: Crohn Disease, A

A 42-year-old man with long-standing Crohn disease

presents to the emergency department with a 1-day

his-tory of increasing abdominal distention, pain, and

obsti-pation He is nauseated and has vomited bilious material

He has no history of abdominal surgery and has had two

exacerbations of his disease this year He is febrile with a

temperature of 38.5°C Examination reveals multiple oralaphthous ulcers, hyperactive bowel sounds, and a grossly distended, diffusely tender abdomen without an apprecia-ffble mass Abdominal radiographs reveal multiple air-fluidfllevels in the small bowel with minimal colonic gas consis-tent with a small bowel obstruction

1 How is inflammatory bowel disease distinguished from infectious diarrhea? fl

•

Inflammatory bowel diseas

e is distinguished fro

infectio

us entities by exclusio

n an

d by t

he following

characteristics:

—Recurren

t episodes o

f mucopurulen

t blood

y diarrhea

(ie, containing mucu

s an

d whit

e cells)

—Lack

of positi

ve cultures for known microb

ial

pathogens

—Failure t

o respon

d to antibiotics alone

•

Perforation, fi stula formatio

n, abscess formatio

n, an

sma

ll intestina

l obstruction

•

Frank bleeding fro

m th

e mucos

al ulceration

s ca

n be

either insidious o

r massive

•

Protein-losin

g enteropathy

•

Increased incidence of intestina

l cancer

•

Extra-intestinal manifestations:

inflammato

in (erythema nodosum), e

ye

(uveitis, iritis), mucous mem

branes (aphth

ile ducts (sclerosing cholangi

tis),

an

d liver (autoimmune chronic acti

ve hepat

itis)

•

Associated diseases: nephrolithiasis, amyloid

osis,

thromboembolic diseas

e, and malnutritio

d granulomatou

s

lesio

ns that occ

ur anywhere alo

ng t

he GI trac

t, most

commonl

y in t

he dist

al ileum with discontinuous area

s

of ulceration and infl ammatio

n involvin

g th

e entir

thickness o

f th

e bowel wall

•

Ulcerative colitis: superficial disea

se limited t

th

e colonic an

d rectal mucosa, with near

ly 100%

involvemen

t o

f th

e rectum

2 What are the differences between ulcerative colitis and Crohn disease? ff

69 Diverticular Disease (Diverticulosis), A

A 76-year-old woman with chronic constipation reports a

4-day history of “achy” left lower quadrant abdominal pain, ft

graded 7/10, accompanied by low-grade fever and nausea

A colonoscopy performed 2 years ago revealed sigmoid

diverticular disease On examination, she has a temperature

of 38.6°C Her abdomen has a tender 3 × 2 cm mass in theleft lower quadrant Bowel sounds are normal Her stool isftpositive for occult blood A CT scan with contrast of theabdomen and pelvis shows pericolonic fat stranding with

no evidence of an abscess She is started on antibiotics

1 Where in the GI tract do most diverticulae occur?

2 What are the major complications of diverticular disease?

•

Most acquired

diverticulae occur in t

he colon; the

descendin

g colo

n an

d sigmoid (left side) a

re involved in ft

mo

re than 90%

of cases

•

Diverticulae a

re a sour

ce of bleedin

g in 3–5% of patients

wit

h diverticulosis, an

d diverticular bleedin

g is t

he most

common cause o

f massi

ve (painless) low

er GI bleedin

g

in t

he elderly

•

Diverticulit

is develops when a foc

al area

of

inflammatio

n occurs

in th

e wall of a diverticulum d

to irritation b

y feca

l material th

at causes abdo

o abscess wi

th

or

witho

ut perforation

•

Approximate

ly 15–25% o

f patients w

ho develo

p

diverticulit

is will require surgery

•

Diverticulosis results fro

m an acquired deformi

ty of

the colo

n in whic

h t

he mucosa and submucos

a hernia

te

throu

gh t

he underlyin

g colonic wall

•

30% of adults in t

he U.S populatio

n are a

ff ected, with ff ff

an increased incidence with age startin

g fr

om about

40 years

•

Epidemiologic studies suggest that th

e consumptio

n of

more highl

y refi ned foo

ds a

nd less fi fiber is ass

ociated fi

with

a higher prevalence of c

hronic constipatio

n ThisTh

consumptio

n may

be responsibl

e for th

e increa

sed

prevalence o

f diverticular disease

•

Constipatio

n lea

ds t

o a transmural pressur

e grad

ient

fro

m colonic lumen t

o peritonea

l space as a resul

t of

vigoro

us muscle contraction o

f t

he colonic wall

•

This functional abnormality is most likely r

ge in dietary habits; decreas

ed dietary fi

ber fi

makes forward propulsio

n of feces a

t norm

lt ffi

3 What predisposing factors contribute to the development of diverticular disease?

70 Irritable Bowel Syndrome, A

A 32-year-old woman comes to the clinic complaining of a

3-month history of abdominal bloating, crampy

abdomi-nal pain, and a change in her bowel habits Previously,

she had regular bowel movements, but 4 months ago, she

developed gastroenteritis with nausea and vomiting after aft

cruise ThTh e constant diarrhea and vomiting went away aftfter

a week, but since then she has had periods of constipation,

lasting up to 3 days, alternating with periods of diarrhea

During the diarrheal episodes, she can have three to four

loose bowel movements per day, without blood or mucus

in the stool She describes diff use abdominal cramping and ffbloating that are somewhat relieved by bowel movements.Her symptoms worsen during periods of stress There has Thbeen no weight loss or fever There is no association withThparticular foods (eg, wheat or dairy products) Her physical examination is unremarkable except for mild abdominaltenderness with no rebound or guarding Serologic tests forceliac sprue are negative Stool cultures and examinationsare negative for bacterial or parasitic infections A colonos-copy is unremarkable

1 List three characteristics of irritable bowel syndrome.

•

A chan

ge in bow

el habits, common

ly alternatin

g

between diarrhe

a an

d constipatio

n, is th

e principal

characteristic o

f irritab

le bowel syndrome

•

Abdomina

l pa

in, which may

be caused b

y inte

stinal

spasms, is als

o commo

n to all patien

ts with irri

tab

le

bow

el syndrome

•

Bloating o

r perceived abdominal disten

•

Irritabl

e bowel syndro

me is a complex disord

er, and

its cause is poorly understo

od, bu

t there a

re ma

ny

theoriz

ed mechanisms

•

Alteratio

ns in sensitivi

ty o

f t

he extrinsic a

nd intrinsic

nervo

us system

s of t

he intestine ma

y contribut

e to

exaggerated sensations

of pa

in an

d t

o abnorm

al control

of intestinal motility

an

d secretion

•

An alteration in the balance of s

ecretion a

nd absorption

is also

a potentia

l cause

•

Although there is no gross infl am

matio

n of t

he intestine

there a

re reports o

f increas

ed infl

ux of infl fl amm

ator

y fl

cells (lymphocytes) into th

e colo

n as well as destructio

n

of enter

ic neuro

ns in a

ff ected individuals ff ff

•

Intestina

l microb

es th

at normall

y inhab

it t

he sma

ll

intestine an

d colo

n may b

e alter

ed as well

, sugg

esting

th

at antibiotics could hav

e a ro

le in treatm

•

Irritabl

e bowel syndro

me may develo

p as a resu

lt

of

an earli

er an

d n

ow resolved bo

ut

of interst

iti

al

infl ammation fl

—In experimental animals, induc

n induces visceral hyp

eralgesia a

altered intestinal motilit

y an

d secretion that

per

sists

man

y months after t

he infl ftam

mation

is res

olved fl

—A simila

r mechanism may o

le bowel syndrome a

fter ft

an infection causing intestinal inflamm

ati

on fl

2 What are possible factors in the pathogenesis of the irritable bowel syndrome?

71 Acute Hepatitis, A

A 28-year-old man, recently emigrating from the

Philippines, was noted to have a positive tuberculin skin

test result in the clinic His chest radiograph showed no

active tuberculosis, and he denied any symptoms of this

infection, including weight loss, cough, or night sweats

To prevent future disease, daily dosing with isoniazid was

recommended for the next 9 months Two weeks afterft

initiating therapy, the patient reported progressive fatigue, intermittent bouts of nausea, and abdominal pain He alsonoticed darkening of his urine and light-colored stools Hissister noted a gradual yellowing of his eyes and skin Blood tests showed a marked increase in serum bilirubin andaminotransferases ThTh e isoniazid was discontinued, and hissymptoms subsided with normalizing of his liver enzymes

1 Describe the range of clinical presentations of acute hepatitis.

•

Th e severity o

f illness in acute hepa

titis ranges fro

asymptomatic clinically ina

pparen

t disea

se t

o fulminant

an

d potentially fat

al liv

er failure

•

So

me patien

ts are relative

ly asymptomat

ic, with

abnormalities noted only

by laboratory studies

•

Sympto

ms a

nd sign

s include anorexia, fatigue, weight

loss, nausea, vomiting, righ

t upp

er quadran

t abdominal

pain, jaundice, fever, splenomegaly,

an

d ascites

•

The extent o

f hepatic dysf

unctio

n ca

tremendously, co

rrelating roughl

y with th

e sev

erit

y

of liv

er injury

•

The relative exten

t of cholestasis vers

us hepatocyt

necrosis is highl

y variable

•

Acu

te hepatitis is commonl

us (HAV), hepatitis B

vir

us (HBV), hepatitis C vir

us (HCV), hepatitis D vir

us

(HDV), an

d hepatitis E virus (HEV)

•

Other viral agen

r virus (cause o

f inf

ectio

us

mononucleosis), cyto

megalovirus, varicella vir

us,

measles vir

us, herp

es simplex vir

us, rubell

a virus,

and yellow fever virus

3 Which viruses can cause hepatitis?

•

Man

y drugs ha

ve been implicated in hepatiti

s

•

Acetaminophen is no

er failur

e in th

e Unite

d Stat

es an

d t

he United

Kingdom

•

Hepatic toxins ca

n b

e furth

er subdivided into those for

whic

h hepatic toxici

ty is predictab

le an

d dose dependent

fo

r most indiv

iduals (eg, acetamino

phen) an

d thos

e th

at

caus

e unpredictab

le (idiosyncratic) reac

o dos

e (eg, nonsteroidal anti-inflam

mator

y fl

drugs suc

h as diclofenac)

•

Idiosyncratic r

eaction

s t

o drugs ma

tible individuals t

o cer

tain

pathways o

f drug metabolism that genera

te t

oxic

intermediates (eg, ison

iazid)

2 How do drugs cause hepatitis?

72 Chronic Hepatitis B, A

A 44-year-old man is concerned about abnormal liver test

results drawn for his pre-employment physical 6 months

ago His serum aminotransferase levels were more than two

times the normal values On further questioning, he has a

distant history of heroin use Currently, he reports some

fatigue but says he feels well otherwise His primary carephysician orders serologic testing, which reveals: HBsAg positive, anti-HBs negative, and anti-HBc IgG positive Anti-HDV and anti-HCV test results are both negative

1 What are the categories of chronic hepatitis based on histologic

findings on liver biopsy?

fi

•

All form

s of chronic hepati

tis exhibit infl ammator

y fl

infiltratio

n of hepatic po

rtal area

s with lymphocyt

an

d plasma cells, and necrosis o

f hepatocyt

es with

in th

e

parenchyma o

r immediatel

y adjacen

t to portal areas

•

In mild chro

nic hepatitis, the overall architectu

re o

f the

liv

er is preserv

ed with

a lymphocyt

e a

nd plasma cell

infiltrate confi fi ned t

o t

he port

al triad withou

t evidence fi

of active hepatocyt

e necrosis or fi

brosis

•

Wit

h progression, t

he port

al are

as expa

nd with dense

lymphocyt

e, histiocyt

e, a

nd plasma cell infi ltra

tion, fi

necrosis o

f hepatocyt

es at t

he lobule per

e around t

he port

al triads

(pieceme

al necrosis)

•

Mor

e sever

e cases also sh

ow evidence of necrosis an

d

fibrosis between portal triads an

rtal area

l are

as (bridgin

g necrosis)

•

Progression t

o cirrhosis is signaled b

y extensi

ve fi

brosis, fi

loss of zonal architectu

re, a

nd regenerating no

du

les

•

Insidious onset o

f nonspecific sympto

ms suc

h as fi

anorexia, malaise,

an

d fatigue

•

Hepatic sympto

ms suc

h as rig

ht upp

er quadrant

abdominal disco

mfo

rt o

r pain

•

Jaundice, if pres

ent, is usuall

y mild

•

Ther

e may b

e mild tender hepato

•

Palma

r erythema an

d spider telangiectasias in sever

e cases

•

Possib

le progression t

o cirrhosis an

d portal

hypertensio

n (ie, ascites, collateral circulatio

n, an

d

encephalopathy)

3 What are the consequences of chronic hepatitis?

•

Infectio

n with sever

al hepatitis viruses (B [with

or

withou

t D] a

nd C)

•

Dru

gs a

nd toxin

s (eg, ethano

l, isoniazid,

acetaminophen), often in amoun

ts insuffi ftcie

nt

to cause ffi

symptomatic acute hepatitis

•

Genetic and metabolic disorders (eg, α

1

-antitrypsin

defi cienc

y, Wilson disea

•

Nonalcoholic fat

ty liv

er disea

se, a chronic li

e metabolic syndrome a

nd ob

esity

•

Systemic disea

ses (e

g, sarcoidosis o

r tuberc

ulosis)

•

V ascula

r injur

y (e

g, ischemia or port

al vein thro

rs)

•

Cholestatic syndromes

•

Immune-mediate

d injur

y o

f unkno

wn origin

2 What are the causes of chronic hepatitis?

73 Cirrhosis, A

A 63-year-old man with a long history of alcohol use

pres-ents to his new primary care physician with a 6-month

history of increasing abdominal girth He has also noted

easy bruisability and worsening fatigue He denies any

his-tory of GI bleeding He continues to drink three or four

cocktails a night but says he is trying to cut down Physical

examination reveals a cachectic man who appears older

than his stated age Blood pressure is 108/70 mm Hg

His scleras are anicteric His neck veins are fl at, and chest fl

examination demonstrates gynecomastia and multiple der angiomas Abdominal examination is significant for a fiprotuberant abdomen with a detectable fluid wave, shiftfl ft ing dullness, and an enlarged spleen The liver edge is diffiTh fficult

spi-to appreciate He has trace pitting pedal edema Laboraspi-tory evaluation shows anemia, mild thrombocytopenia, and

an elevated prothrombin time Abdominal ultrasonogram confi rms a shrunken, heterogeneous liver consistent withficirrhosis, significant ascites, and splenomegaly.fi

1 What are the defi ning features of cirrhosis? fi

•

All form

s of cirrhosis are c

haracterized by three

fi ndings: fi

—Mark

ed distortio

n of hepatic architecture

—Scarrin

g as a resul

t of increas

ed depositio

n of fi

brous fi

tissue a

nd collagen

—Regenerative nodules surrounded by scar

tissue

•

Portal hypertensio

n due t

o increas

ed intrahepatic

vascular resistan

ce from scarring

•

Ascites (excess fl

uid within t

he abdominal cavi

•

Hepatorena

l syndro

me (kidney injury resultin

g from

rena

l vasoconstriction that develops in respon

se to

arterial vasodilation in advanced liver disease)

•

Hypoalbuminemia, peri

pheral edema, an

d electrolyte

abnormalities (eg, hyponatremia)

•

Spontaneo

us bacterial peritonitis

•

Gastroesophage

al varices a

nd bleeding

•

Hepatic encephalo

pathy

•

Coagulopath

y (d

ue to decreased hepatic pro

duc

tion o

f

clottin

g factors)

•

Splenomegaly a

nd hypersplenism (inclu

din

g

thrombocytopenia)

•

Hepatocellula

r carcinoma

•

Hepatopulmonary syndro

me an

d portopulmo

nary

hypertension

3 What are the major clinical manifestations of cirrhosis?

•

Exac

t mechani

sm i

s unknown

•

Chronic alcohol us

e has been associated with impaired

protein synthesis, lipi

d peroxidatio

n, an

d t

he formation

of acetaldehyde

, whic

h may interfer

e with memb

rane

lipi

d integrity and disru

pt cellular function

•

Local hypoxia, as well

as cell-mediate

ted

2 What are some ways alcohol may injure the liver?

74 Acute Pancreatitis, A

An admitting physician is called to the emergency

depart-ment to evaluate a 58-year-old woman with a 2-day history

of fever, anorexia, nausea, and abdominal pain Suspecting

pancreatitis, the physician inquires about a history of

similar symptoms She had been seen 2 months ago in

the emergency department for an episode of unrelenting,

achy right upper quadrant abdominal pain At the time,

an ultrasound imaging demonstrated multiple gallstones

without evidence of cystic duct obstruction or gallbladder

wall edema Now, serum amylase and lipase levels are both grossly elevated She is diagnosed with acute pancreatitis

On day 3 of her hospitalization, the physician is calledurgently to evaluate her for hypotension, shortness of breath, and ensuing respiratory failure She requires endo-tracheal intubation and mechanical ventilation A chestradiograph and severe hypoxia support the diagnosis of acute respiratory distress syndrome

1 What are the presenting symptoms and signs of acute pancreatitis?

e criteria hel

p establish

the diagnosis o

f acute pancreatitis: abdominal pa

in,

elevatio

n of serum amylase o

r lipas

e (more th

an thre

e

times t

he upper limi

t of normal), an

d characteristics

fi ndin

gs on

CT (or MRI o

r ultraso

•

Sign

s and sympto

ms include:

—Abdominal pain: intense, deep, searing pa

in with

radiatio

n t

o t

he back

—Naus

ea a

nd vomiting

—Fever d

ue to extensive tissue inju

ry, inflam

matio

n, fl

and release o

f interleukin (IL)-1 a

nd other c

yto

kines

—Elevatio

n of serum amylase and/o

r lipase

3 What are the complications of severe pancreatitis?

•

Shock fro

m retroperitonea

l fluid loss/bleedin

r coagulation (DIC)

•

Acu

te respiratory distress syndrome (ARDS)

•

Necrotizin

g pancreatitis with possible infectio

n

•

Pancreat

ic pseudocyst formation

•

Pancreat

ic ascites a

nd fi stula

s fi

•

Biliary tract disease: gallston

es, sludge

•

Alcohol intake: binge, alcoholism

•

Trauma: blun

t abdominal trauma, p

ostoperative,

postprocedural, electric shock

•

Infections: man

y vira

l, bacteria

l an

d parasitic causes

•

Metabolic: hyperlipidemia, hypercalcemia, uremia,

pregnancy, malnutrition,hemochromatosis, diabetic

ketoacidosis

•

Hereditary: familial pancr

eatitis, cystic fi brosis fi

•

Poison

s an

d toxins: veno

m, organophosphates, zinc,

cobalt, mercuric chloride

•

Drugs: numerous medications

•

V ascular: vasculit

is, shock, atheromatous embo

lis

m

•

Mechanical: pancreas divisum, tumo

r, stenosis of t

he

ampulla o

f Vate

r, penetrating duodenal ulcer

2 What are the most common causes of acute pancreatitis?

75 Chronic Pancreatitis, A

A 52-year-old man with a 20-year history of alcohol abuse

presents to his primary care provider complaining of

recurrent episodes of epigastric and left upper quadrant ft

abdominal pain Over the past month, the pain has become

almost continuous, and he has requested morphine for

bet-ter pain control He has a history of alcohol-related acute

pancreatitis Examination reveals a 10-pound weight lossover the past 6 months He has some mild muscle guarding over the epigastrium with tenderness to palpation Bowel sounds are somewhat decreased Serum amylase and lipaseare mildly elevated A plain film of the abdomen demon-fistrates pancreatic calcifications.fi

1 What are causes of chronic pancreatitis?

•

Chronic alcoholism accounts

for abou

t 70–80% of cases

•

Cigaret

te smokin

g is a stro

ng independent risk factor

fo

r t

he developmen

t o

f chronic pancreatitis; the

combination

of signifi ca

nt alcohol a

nd cigaret

te us

appears

to b

e synergistic in augmen

ting t

he risk

of

chronic pancreatitis

•

Chronic pancreatitis ca

n also b

e caused b

y long-term

obstructio

n o

f t

he pancreatic du

ct, e

g, fro

m neoplasm,

papillary stenosis, cystic

lesio

ns (cystic tu

mors

or

pseudocysts), scarrin

g o

r strictu

re, trauma, or pa

ncreas

divisum

•

Tropica

l chronic pancreatitis is a ju

c calcific pancreatitis, though

nd micronutrient deficiencies, o

use pancreatitis, w

hich is

seen in 10–15% o

f patients with hyperpara

ry pancreatitis accounts

•

Other cas

es can b

e autoimmune o

r idiopat

hic or r

ela

ted

to dru

gs (medication

s)

•

Lithostathines are pancreatic juice peptides that inhibit

the formation

of protein plugs and th

e aggregatio

n of

calci

um carbonate crystals t

o form stones

—Alcoho

l impair

s secretion o

f lithostathines

—Furthermo

re, when hydrolyzed by trypsin a

nd

cathepsin B, lithostathine H2/PSP

-S1 is created and

it polymerizes into

th

e matr

ix of protein plugs

—Also, there is hypersecretion o

f calci

um into the

pancreat

ic juice

—Th

e formatio

n of protein plugs in pancrea

that

is thick, visci

d, and protein-rich, cou

ple

d

wit

h a calci

um carbonate concentra

d leads t

o formatio

n of calculi (sto

nes)

•

Lactoferrin, a

n iron-containing macromolec

ular

protein, is elevate

d in t

he pancreatic secretion

s o

f

alcoholic patien

ts with pancreatitis

—Lactoferrin ca

n produce clum

ps of large p

of protein plugs

3 How is alcohol thought to cause chronic pancreatitis?

•

Severe abdominal pain that can b

e constan

t or

intermittent

•

Nausea an

d vomiting

•

W eig

ht loss and malabsorption

•

Hyperglycemia a

nd diabet

es mellitus

•

Jaundice

•

Pancreatic parenchymal and/o

r main duct

76 Pancreatic Insuffi ciency, A

A 15-year-old boy with a history of cystic fibrosis comesfi

to see you due to worsening diarrhea and weight loss

His lung disease has been relatively well controlled, but

recently he has lost 5 kg unintentionally His stools have

also become loose and are very bulky, greasy, and foul

smelling, especially after fatty meals On examination,ft

he is thin but otherwise normal appearing His weight

is 45 kg and his height is 160 cm (yielding a body mass index of 17.6 [underweight]) Lung exam is notable for scattered rhonchi and crackles, but the rest of the exami-nation, including the abdominal examination, is normal Stool collection verifies the presence of steatorrhea He is fistarted on pancreatic enzymes with resolution of his gas-trointestinal symptoms

1 What are the symptoms and signs of pancreatic insuffi ffi ciency?

•

Steatorrhea: volumino

us or bulky, foul-smellin

g, greasy,

froth

y, pale yello

w, a

nd floatin

g stoo

ls fl

—Mild cases ma

y require a 24-ho

ur feca

l f

at collection

fo

r diagnosis

—Sever

e cases ma

y le

ad to fat-solub

le vitamin

defi ciencies (vitamin

s A, D, E, a

•

Diarrhea: unabsorbed hydroxylated fat

ty aci

ds are

cathartic

•

W eig

ht loss

•

Hypocalcemia: deficiency o

f vitamin D coup

led with fi

th

e binding o

f dietar

y calci

um to unabsorb

o hypocalcemia

•

Nephrolithiasis: binding o

f dietary calcium to

unabsorbed fatty aci

ds results in excessive

inte

stinal

absorption o

f dietar

y oxalat

e and kidney ston

e

formation

•

Vitamin B

12

defi cienc

y fi

•

Pancreat

ic lipas

e is essential f

or fa

t digestion; its absence

lea

ds t

o f

at malabsorption

•

Although pancreatic amylase and trypsin are importa

nt

for carbohydrate an

d protein digestion, t

he presence of

these enzymes in gastr

ic an

d intestinal juice ca

n usually

compensat

e f

or pancreatic deficiencies fi

•

Th us, patients wi

th pancreatic in

ciency seldo

m ffi

present with malabsorption

of carbohydrate

•

Neoplasm o

r resectio

n of pancreas

•

Severe protein-calorie malnutritio

n, hypoalbuminemia

•

Cystic fibrosis, hemochro

matosis, Shwachman fi

syndrome, enzyme defici

encies fi

•

Non-tropical spru

e, gastrinoma

•

Gastr

ic surgery

2 What are the causes of pancreatic insuffi ciency? ffi

77 Carcinoma of the Pancreas, A

During a family reunion, a 62-year-old widower describes

to his son a 1-month history of lethargy He attributes it

to the stress of a recent move from a large

three-bed-room house into an apartment His granddaughter

com-ments that his eyes appear “yellow” and that he has lost a

signifi cant amount of weight since their last visit with him.fiCorroborating the finding of painless jaundice, his inter-finist orders a contrast-enhanced spiral CT, revealing a 3-cmmass in the head of the pancreas

1 What are the risk factors for pancreatic cancer?

•

Cigaret

te smokin

g is though

t to accoun

t fo

r o

ne quarter

of diagnosed cases

—N-nitros

o compounds in ciga

al hyperplasia, a po

ssible precurso

r

to adenocarcinoma

•

Oth

er ris

k facto

rs include: a hig

h dietar

y inta

ke o

f

saturate

d fat, a

nd exposur

e to nonchlorinated solvents

and t

he pesticide dichloro

diphenyl trichloroethane

(DDT), although th

e overa

ll contributio

n of thes

e

facto

rs is likely small

•

Diabetes mellitu

s has also recently been identified as fi

a risk facto

r for th

e disease

•

Chronic pancreatitis increa

ses t

he risk

ic adenocarcino

ma by 10- t

o 20-fold

•

Diets containin

g fresh fruits a

nd vegetab

•

Ther

e is an increased incidence o

f pancreatic ca

amon

g patien

ts with heredita

ry pancreatitis, pa

rtic

ular

ly

amon

g those with pancreatic calcificati

ma is inherited

•

The majori

ty of patients wi

th pancr

adenocarcino

ma d

o not hav

e ris

k factors

•

A thin-cu

t helical CT scan

or endoscop

ic ultrasound

wit

h fi

ne needle aspiratio

f t

he biliary

or pancreatic duct

als

o may b

e useful

•

A variet

y o

f tumo

r markers ca

n be found in t

he s

eru

m

of patients with pancreatic cancer b

ut have p

oo

r test

sensitivi

ty a

nd specifici

ic cancer ma

y present lik

e chronic pancreatitis

•

Patien

ts with carcino

ma of t

he he

ad of t

he pancreas

usuall

y present with painless, progressive jaundice,

resulti

ng fro

m commo

n bile duc

t obstructio

n and/or a

dilated gallbladder palpa

ble in th

e righ

t upp

er quadrant

(Courvoisier law)

•

Patien

ts with carcino

ma of t

he bo

dy o

r tail

of the

pancreas usually present with epigastr

ic abdomina

l pa

in,

profound weigh

t loss, abdominal mass, an

d anemia

—Th es

e patien

ts usually present a

t later stages a

often ha

ve distan

t metastases, particularl

y in th

e live

—Splenic vein th

rombosis may occur as a comp

licati

on

of cancers in t

he bo

dy o

r tail

of t

he glan

d

•

Abou

t 70% of patients with pancreatic cancer h

ave

impaired glucos

e tolerance o

r fran

k diabetes melli

tu

s

2 What are common symptoms and signs of pancreatic cancer?

78 Acute Kidney Injury: Acute Tubular Necrosis, A

A healthy 26-year-old woman sustained a significantfi

crush injury to her right upper extremity while on the job

at a local construction site She was brought to the

emer-gency department and subsequently underwent pinning

and reconstructive surgery and received perioperative

broad-spectrum antibiotics Her blood pressure remained

normal throughout her hospital course On the secondhospital day, a medical consultant noted an increase in her serum creatinine, from 0.8 to 1.9 mg/dL Her urine outputdropped markedly to 20 mL/h Serum creatine kinase was ordered and reported as 3400 units/L

1 What are the current theories for the development of acute tubular necrosis?

•

Th eories favorin

g eith

er a tubular o

r vascula

r etiolog

hav

e been proposed

•

T ubular theory: occlusio

n of t

he tubular lumen with

cellula

r debris form

s a cast th

at increases intratubular

pressur

e suffi ciently to off ffiset p

erfusio

n pressur

e an

decreas

e o

r abolis

h net

fi ltration pressu

re fi

•

V ascular theory: decreased ren

al perfusion

pressur

e fro

m t

he combination

of a

ff erent arteriola

r ff ff

vasoconstriction a

nd eff erent arteriolar vasodilatio

reduces glomerular perfusio

n pressur

e an

d, therefore,

glomerular fi ltration fi

•

Both mechanisms ma

y ac

t to produce acute kidne

y

inju

ry, varying in relative importan

ce in differe

nt ff ff

individuals depending o

n t

he cause and time of

presentation

•

Renal damage, whether caused b

y tubula

r occ

lusio

n or

vascular hypoperfusio

n, is potentiated b

h increas

es isch

emia

•

Cytokines a

nd endogeno

us peptides suc

h as endothelin

s

an

d activatio

n of complement a

nd neutro

phils incr

eas

e

vasoconstriction furth

er an

d wors

en injury

•

Acu

te kidney injury: th

e most widely accepted

defi nition is a rise

in ser

um creatinine of fi

≥0.3 mg/dL

within a 48-hour

period o

r a fall in urine ou

tp

ut t

o less

than 0.5 mL/k

g/h for

at least 6 hours

•

On th

e oth

er hand, imaging o

f t

he kidneys in chro

nic

kidney diseas

us creatinine value is hel

te a

nd chronic kidney dis

ease

3 What clues are helpful in determining whether newly diagnosed kidney disease

is acute or chronic?

•

Th e initial symp

to

ms a

re typically fatigue an

d malais

probably earl

y consequences of loss o

f t

he abili

ty to

excrete water, salt, a

nd wast

es via th

e kidneys, o

ft en with ft

decreas

ed urine output

•

Lat

er, mo

re profound sympto

ms a

nd sign

a,

orthopne

a, rales, a prominent thir

d heart sound (S

3

),

and peripheral edema

•

If t

he cause is prerenal azotemia, t

his ca

n oft

rapidl

y revers

ed before progression t

o acute t

ub

ula

r

necrosis tak

es place

•

Altered mental status reflects t

he toxic eff flect o

f ur

emia ff ff

on th

e bra

in, with elevated blood leve

ls of nitro

om acute tubula

r necrosis, if i

t o

ccu

rs,

follows a protracted course, oft

en requirin

re adequate renal function is rega

ined

2 What is the natural history of acute kidney injury?

79 Chronic Kidney Disease, A

A 58-year-old obese woman with hypertension, type 2

diabe-tes, and chronic kidney disease is admitted to a hospital afterft

a right femoral neck fracture sustained in a fall Recently,

she has been complaining of fatigue and was started on

subcutaneous injections of epoetin alfa Her other

medica-tions include an angiotensin-converting enzyme

inhibi-tor, a β-blocker, a diuretic, calcium supplementation, and

insulin On review of systems, she reports mild tingling in her lower extremities On examination, her blood pressure is 148/60 mm Hg She is oriented and able to answer questionsappropriately ThTh ere is no evidence of jugular venous disten-tion or pericardial friction rub Her lungs are clear, and herright lower extremity is in traction in preparation for sur-gery Asterixis is absent Her serum creatinine is 3.9 mg/dL

1 What are the most common causes of chronic kidney disease (CKD)?

•

In developed countries, t

he most common ca

use o

f

CKD is diabet

es mellitus

•

Hypertensio

n an

d glomerulonephritis a

re t

he second

and third most frequent causes o

f CKD, respectively

•

Less common ca

uses are: polycystic kidne

y dis

eas

e,

interstitial nephritis, obstruction, and infection

•

Patien

ts with CKD typicall

y ha

ve some degre

e of Na

an

d water excess, refl

ectin

g loss of t

he renal salt an

wat

er excretion in t

he face o

f ongoing intake

ed renal salt an

conservatio

n mechanisms, s

o they are mo

re sensitive

than norm

al t

o sudden extrarena

l Na

+

and water loss

es

(eg, vomitin

g, diarrhe

a, an

d increased cuta

neous loss

es

such

as with fever)

•

Hyperkalemia is a seri

ou

s problem in CKD, especia

lly

for patien

ts whose GFR has fallen belo

w 5 mL/min when

compensatory mechanisms f

or potassium excretio

n

(such

as aldosterone-mediated K

+

transport)

fai

l

3 What is the mechanism by which altered sodium, potassium, and volume

status develop in chronic kidney disease?

•

Uremia is a syndr

ome characterized by a uniq

ue set

of sympto

ms, physical examinatio

n findings, a

nd fi

laboratory abnormalities presumably caused b

y a

accumulatio

n o

f o

ne

or more uncharacterized toxins

•

Symptoms: fatigue, confusion, lethargy, asterixis,

periphera

l neuropath

y, seizures, co

ma, pruritus,

anorexia, nausea, a

nd vomiting

•

Examinatio

n findings: pericardial ru

b, ecchymos

pulmonary edema, hypotension, myoclonus, s

eizures,

osteomalacia/osteop

orosis, peripheral edema a

nd

ascites, a

nd malnutrition

•

Laboratory findings: hyponatremia, hyperkalemia, fi

hyperphosphatemia, secondary hyperparath

yro

id

ism,

anemia, leukopenia, and thrombocytopenia

2 What is uremia?

80 Poststreptococcal Glomerulonephritis, A

A 28-year-old nursery school teacher developed a marked

change in the color of her urine (“cola-colored”) 1 week

aft er she contracted impetigo from one of her students ft

She also complained of new onset of global headaches

and retention of fluid in her legs Examination revealed afl

blood pressure of 158/92 mm Hg, resolving honey-crusted

pustules over her right face and neck, and 1+ pitting edema

of her ankles, with no cardiac murmur Urinalysis revealed

2+ protein and numerous red cells and red cell casts Her serum creatinine was elevated at 1.9 mg/dL Serum com-plement levels (CH50, C3, and C4) were low She was diag-nosed with poststreptococcal glomerulonephritis

1 What are common infectious causes of glomerulonephritis (GN)?

•

Infectio

ns with certa

in “nephritogenic

” strain

s of group

A beta-hemolytic streptococci

—I

n poststreptococcal GN, ther

e is a lag (7–10 days)

between clinica

l sign

s of infection and developmen

t

of clinica

l sign

s of nephritis

•

Subacu

te bacterial endoca

rditis (SBE) is ano

ther ca

use

•

Poststreptococcal GN a

nd S

BE ca

n produce ac

ute GN o

r

rapidl

y progressive

GN (RPGN)

•

Viral infectio

ns wi

th hepatitis B virus a

nd h

uma

n

immunodeficiency vir

us (HIV) can als

o pro

duce RPGN fi

•

Acu

te GN is a

n abru

pt onset o

f hematuria and proteinuria

wit

h reduced G

FR an

d renal salt an

d water retention

—Complet

e recover

y o

f renal function sometimes occu

GN in which t

her

e is a

progressive decline (week

s to months) in rena

l functio

n,

often leading t

o complete renal failur

e an

d oligur

—Earl

y disea

se ca

n b

e subt

le but

is marked

by

proteinuria a

nd hematuria, followed b

y decreas

ed GFR

—Th

is is o

ft Th

en called “crescentic GN” since t

characteristic

fi nding o

n biopsy is cellula

r cres

in t

he Bowma

n space

—Cellula

r crescen

ts, visible o

n lig

ht microsco

py, f

orm

in respon

se t

o sever

e damag

e to th

e glomeru

lar

capillaries, a nonsp

ecifi

c fi fi nal pathway in a variety o

glomerula

r diseases

—Recovery

is rare withou

t specifi

c treatm

us GN, there is cross-rea

ctivit

y between

an antigen o

f t

he infectin

g organism a

nd a host anti

gen,

resultin

g in depositio

n of immune com

plex

es an

d

complemen

t in th

e kidney’

s glomerular capillaries and

mesangium

•

Thes

e are found as “humps

” in th

e subepithelial space Th

•

Resolutio

n of glomerula

r disea

se typicall

t of th

e original infectio

2 What is the pathophysiology of poststreptococcal GN?