Pemicu 3

1st LO (1)
• Histology of large intestine
Large intestine
Appendix
-. Fewer glands

-. No taenia coli

-. The laminar propria and

submucosa are generally
filled with lymphocytes and
lymphoid follicles, making
the appendix a significant
part of the MALT
Recto-anal junction
1st LO (2)
• Anatomy of large intestine
Large intestine
Arterial supplies
Veins & lymph node
Innervations
Cecum & appendix Cecum

-. Has no mesentery
-. Lies in the iliac fossa
inferior
-. If distended with feces or
gas  palpable
-. Ileocolic artery

Appendix

-. Position: retrocecal
-. Has short triangular
mesentery  mesoappendix
-. Appendicular artery
Rectum
• The pelvic part of the alimentary tract and is continuous
proximally with the sigmoid colon and distally with the anal canal
• The rectosigmoid junction lies anterior to the S3 vertebra
• The rectum follows the curve of the sacrum and coccyx, forming
the sacral flexure of the rectum
• Ends anteroinferior to the tip of the coccyx, immediately before a
sharp posteroinferior angle (the anorectal flexure of the anal
canal)
• The roughly 80° anorectal flexure  fecal continence, being
maintained during the resting state by the tonus of the
puborectalis muscle and by its active contraction during
peristaltic contractions if defecation is not to occur
Arteries & veins
Lymph drainage
Innervation
1st LO (3)
• Physiology of intestine
Small intestine
• Divided into three segments—the duodenum,
the jejunum and the ileum
• Motility
▫ Segmentation  Segmentation contractions mix
and slowly propel the chyme
▫ Migrating motor complex  weak, repetitive
peristaltic waves that move a short distance down
the intestine before dying out
• The waves start at the stomach and migrate down the
intestine; that is, each new peristaltic wave is initiated
at a site a little farther down the small intestine.
• After the end of the small intestine is reached, the
cycle begins again and continues to repeat itself until
the next meal
• The migrating motility complex is regulated between
meals by the hormone motilin, which is secreted
during the unfed state by endocrine cells of the small-
intestine mucosa.
• Small-intestine secretions do not contain any digestive
enzymes
• The small intestine does synthesize digestive enzymes, but
they act within the brush-border membrane of the epithelial
cells that line the lumen instead of being secreted directly
into the lumen
• Digestion within the small-intestine lumen is accomplished
by the pancreatic enzymes, with fat digestion being
enhanced by bile secretion.
• Thus, fat digestion is completed within the small-intestine
lumen, but carbohydrate and protein digestion have not
been brought to completion
• Special hairlike projections on the luminal
surface of the small-intestine epithelial cells, the
microvilli, form the brush border. Contain
three categories of integral proteins that
function as enzyme :
▫ Enterokinase
▫ Dissacharidases (maltase, sucrase, and lactase)
▫ Aminopeptidase
• Biochemical balance among the stomach, pancreas,
and small intestine is normally maintained
• HCl + NaHCO3  NaCl + H2CO3
• The resultant H2CO3 decomposes into CO2 + H2O:
• H2CO3 + CO2  H2O
• The end products of these reactions—Na, Cl, CO2,
and
• H2O—are all absorbed by the intestinal epithelium
into the blood.
LO 2
• Capable to explain diarrhea
Diarrhea
• Passage of abnormally liquid or unformed stools at an
increased frequency
▫ Pseudodiarrhea ~ frequent passage of small volumes of
stool, is often associated with rectal urgency and
accompanies IBS or proctitis
▫ Fecal incontinence ~ involuntary discharge of rectal
contents and is most often caused by neuromuscular
disorders or structural anorectal problems

• For adults on a typical Western diet, stool weight

>200 g/d can generally be considered diarrheal

▫ Acute: < 2 weeks

▫ Persistent: 2-4 weeks
▫ Chronic: > 4 weeks
Acute diarrhea
• 90% of cases of acute diarrhea are caused by
infectious agents
• Accompanied by vomiting, fever, and abdominal
pain

• 10% or so are caused by medications, toxic

ingestions, ischemia, and other conditions
Risk factors
• Travelers
▫ Enterotoxigenic or
enteroaggregative
Escherichia coli as well as
to Campylobacter,
Shigella, Aeromonas,
norovirus, Coronavirus
and Salmonella
▫ Giardia, Cyclospora
• Consumers of certain foods
▫ Salmonella,
Campylobacter, or
Shigella
▫ Vibrio species, or acute
hepatitis A
• Immunodeficient persons
▫ Mycobacterium species
▫ viruses (cytomegalovirus,
adenovirus, and herpes
simplex)
▫ protozoa
(Cryptosporidium,
Isospora belli,
Microsporida, and
Blastocystis hominis)
• Daycare attendees and their
family members
▫ Shigella, Giardia,
Cryptosporidium, rotavirus
• Institutionalized persons
▫ C. difficile
Treatment
• Fluid (mild cases) and electrolyte replacement
▫ Oral sugar-electrolyte solutions  severe diarrhea
▫ dehydrated patients, especially infants and the elderly  IV
rehydration
• Antimotility and antisecretory agents such as loperamide
(CI: febrile dysentery)
• Bismuth subsalicylate
▫ reduce symptoms of vomiting and diarrhea
• Judicious use of antibiotics
▫ quinolone, such as ciprofloxacin (500 mg bid for 3–5 d)
▫ giardiasis with metronidazole (250 mg qid for 7 d)
▫ Antibiotic prophylaxis  travelling patients
(immunocompromise, IBD, hemochromatosis, gastric
achlorhydria)
▫ trimethoprim/sulfamethoxazole, ciprofloxacin, or rifaximin
 reduce bacterial diarrhea
Approach to the patient
Chronic diarrhea
Secretory diarrhea
• Due to derangements in fluid and electrolyte
transport across the enterocolonic mucosa
• Watery, large-volume fecal outputs that are
typically painless and persist with fasting
• No malabsorbed solute  stool osmolality is
accounted for by normal endogenous
electrolytes with no fecal osmotic gap
Osmotic diarrhea
• Occurs when ingested, poorly absorbable,
osmotically active solutes draw enough fluid into
the lumen to exceed the reabsorptive capacity of
the colon
• Fecal water output increases in proportion to
such a solute load
• Ceases with fasting or with discontinuation of
the causative agent
Steathorrea
• Fat malabsorption 
▫ greasy,
▫ foul-smelling,
▫ difficult-to-flush diarrhea
▫ often associated with weight loss and
▫ nutritional deficiencies due to concomitant
malabsorption of amino acids and vitamins
• Steatorrhea is defined as stool fat exceeding
the normal 7 g/d
• e/  Intraluminal maldigestion, mucosal
malabsorption, or lymphatic obstruction
Physical examination
• Are there general features to suggest malabsorption or
inflammatory bowel disease (IBD) such as anemia, dermatitis
herpetiformis, edema, or clubbing?

• Are there features to suggest underlying autonomic neuropathy

or collagen-vascular disease in the pupils, orthostasis, skin,
hands, or joints?

• Is there an abdominal mass or tenderness?

• Are there any abnormalities of rectal mucosa, rectal defects, or

altered anal sphincter functions?

• Are there any mucocutaneous manifestations of systemic

disease such as dermatitis herpetiformis (celiac disease),
erythema nodosum (ulcerative colitis), flushing (carcinoid), or
oral ulcers for IBD or celiac disease?
Approach to the patient
Treatment
• Depends on the specific etiology and may be curative,
suppressive, or empirical
▫ elimination of dietary lactose for lactase deficiency or gluten
for celiac sprue
▫ glucocorticoids or other anti-inflammatory agents for
idiopathic IBDs
▫ adsorptive agents such as cholestyramine for ileal bile acid
malabsorption
▫ proton pump inhibitors (omeprazole)  gastric
hypersecretion of gastrinomas
▫ somatostatin analogues (octreotide)  malignant carcinoid
syndrome
▫ prostaglandin inhibitors (indomethacin)  medullary
carcinoma of the thyroid
▫ pancreatic enzyme  pancreatic insufficiency
▫ Mild opiates (diphenoxylate or loperamide)  in mild or
moderate watery diarrhea
3rd LO
• Capable to explain the etiology of diarrhea
Protozoal diarrhea
• Cryptosporodiosis
• Isosporiasis
• Cyclospora
• Amebiasis
• Giardiasis
• Blastocystis
Cryptosporodiosis
• Ex: Cryptosporidium parvum
• Oocysts contain naked sporozoites not surounded by
sporocyst
• Was likely a cause of human diarrheal disease ( Nime
et al. 1976)
• Normal & immunocompromised patients were
suspectible to diarrhea caused by cryptosporodiosis
• ~60% from AIDS patient’s stool
Life Cycle
Pathogenesis: intestinal disease
• Not well understood (~alters intestinal epithelial
cells function as well as the enteric immune &
nervous system)
• Host imunity
▫ Cell mediated  CD4+ T cell
▫ Humoral  IgG, IgM, IgA

• Higher-intensity infection  more severe gut injury

▫ Villous atrophy & fusion
▫ Crypt hiperplasia
▫ Cellular submucosal infiltration (PMN & MN)
▫ Evidence of carbohydrate, protein & vitamin (B12)
malabsorption
▫ Reduced activity of brush border enzyme (lactase, sucrase)
Clinical features
• 2 major syndromes
▫ Immunocompetent 
 Acute watery self limited diarrhea,
 Nausea, vomiting, fecal urgency, abdominal cramps
& discomfort
 Low or high grade fever
▫ Immunocompromised 
 Life-threatening diarrheal illness, relapsing diarrhea
 Biliary tract infection
DD
• Other protozoan infections
• Non invasive bacterial infections
(enterotoxigenic E. Coli)
• Viral infections (norwalk & rotavirus)
• Immunocompromised diarrhea
Laboratory diagnosis
• Stains
▫  modified Ziehl-Neelsen, Kinyoun acid
▫ Oocysts must be differentiated from yeasts and
larger oocysts
• PCR
• Serology
▫ ELISA  detect IgG, IgM antibodies
▫ Elevated IgM in 2 weeks
Treatment
• Oral rehydration solution
• Nitazoxanide
• AIDS patients 
▫ Paramomycin (1g twice daily) & azithromycin
(600 mg twice daily)
▫ Prophylaxis  Clarithromycin & Rifabutin
Prevention
• Avoidance of contact with human & animal feces
in water and food
• Avoidance of sexual practices
• Handwashing
• Avoidance of lakes’ & rivers’ water ingestion
• Infected patients must avoid swimming on the
public swimming pool
Isosporiasis
• Ex: Isospora belii
• Invades the host cell’s cytoplasm restricted to the apical surface of
the cell  the excreted oocysts not fully sporulated  not
immediately infective for man
• Most cases  oocysts’ maturation occurs outside the human host &
amplification of the infection in human (autoinfection ~C.
parvum)

• Epidemiology
▫ From tropical & subtropical areas
▫ Transmitted by contaminated food or water; person-person  oral-
anal contact
▫ AIDS  persistent & chronic diarrhea
Life cycle
Pathogenesis & Immunology
• Infection on the intestinal epithelium 
▫ Flattened mucosa
▫ Shortened villi
▫ Hypertrophic crypts
▫  malaobsorption of fat, protein, sugar, & vit B12
• Parasite developmental stages are found
predominantly within the epithelial, and rarely in
lamina propria or submucosa
• Inflamation in lamina propria
▫ MN, PMN, eosinophils
Clinical features
• A non spesific watery diarrheal illness, +
abdominal cramps, nausea, malaise, anorexia,
weight loss
• Severe illness  dehydration (6 liters of stool)
• Strikingly protracted illness
• Malabsorption
• AIDS
▫ Disseminated infection
Laboratory diagnosis
• I. belii oocysts are acid-fast (Rhodamine-Auramine)
• Contains 2 sporoblasts

• Intestinal biopsy  developmental stages of parasite

• Stimulate eosinophils on the lamina propria with

contaminant Charcot-Leyden crystals detectable in
stool samples
• mild to moderate systemic eosinophilia, absence of
leukocytes
Treatment & Prevention
• Maintaining adequate hydration parenterally
• Drug of choice  Cotrimoxazole  resolution of
diarrhea for 2 days
• Ciprofloxacin (500mg twice daily for 7 days) 
intolerate Cotrimoxazole

• Prevention
▫ Resistant to many disinfectans
▫ survive for months in the environment under moist,
cool condition
Cyclospora
• An acid-fast, autofluorescent large Cryptosporidium like
parasite in the stools of a patient with HIV infection

• Epidemiology
▫ Seasonal occurence of infections among expatriates in Nepal
▫ Association with drinking contaminated water & with foods
such as imported raspberries, mesclun lettuce and basil
▫ Require an obligatory phase of maturation in the
environment after they are excreted in the feces
▫ Unlikely to be transmitted directly from person to person
▫ Seasonality infection
Life cycle
Pathogenesis
• Oocysts excyst in the small bowel  sporozoites
invade enterocytes
• Histopathologic change 
▫ Villous blunting (widening & shortening of the
small intestinal villi due to diffuse edema)
▫ Crypt hiperplasia
▫ Inflammatory infiltration in the lamina propria
with reactive hyperemia
▫ Vascular dilatation & capillary congestion
Clinical features
• Substantial symptoms of
▫ Diarrhea
▫ Striking fatigue
▫ Weight loss
▫ Abdominal cramps
Laboratory diagnosis & Treatment
• Direct acid-fast stain / microwave-heated safranin
staining of fecal specimen
• PCR

• Treatment
▫ Cotrimoxazole b.i.d
▫ Tinidazole, diloxanide, quinacrine, azithromycin 
Ineffective
▫ Trimethoprim  patient who allergic to sulfametoxazole
▫ Ciprofloxacin
Prevention & control
• Detection of infection
• Viable oocysts in food and water supplies
• Avian or mammalian fecal contamination of
fresh fruits & vegetables that are eaten raw
remain paramount in preventing transmission
• Oocysts resistant to chlorine / water disinfection
Amebiasis
• Ex: Entamoeba histolytica
• Invasive & causes disease such as colitis & liver abcess
• Ameba in the stool of a young farmer with dysentery
(Fedor Losch, 1873)
• Morphology  round, pear-shaped / irregular form,
almost continuous motion
• Infective form  cyst form

• Epidemiology
▫ Children or farmworkers  exposed to human wastewater
used to irrigate crops
Morpholgy of trophozoite & cyst
Life cycle
• Infective cyst & invasive trophozoite form

• Quadrinucleate cyst (infective form)

▫ Resistant to chlorination
▫ Gastric acidity & dessication
▫ Can survive a moist environment for several weeks
▫ Infection occurs due to fecal-oral spread with fecally
contaminated food or water
▫ Excystation occurs in the intestine  8 trophozoites
• Trophozoite stage
▫ Colonize / invade large bowel  formation of flask-shaped ulcer
▫ Migration via portal vein  hepatic abscesses
Pathogenesis
• Carbohydrate-protein interactions
• Gal/GalNAc-lectin
▫ Lectin not inhibited by Gal/GalNAc  mediated
adherence & cytolysis activity
▫ Resistant to C5b-9 complement complexes
• Pore-forming protein  cytolytic activity
• Colagenase  proteolytic activity
• Interaction between the trophozoites & colonic mucins
▫ Induce secretion of colonic mucins
▫ Degrading colonic mucins
Immunology
• Anti-E. histolytica
• < B cell & T cell  amebic liver abcesses
• Cell mediated immunity  cytokine activation of
macrophages & neutrophils
 • Liver abscess
Clinical features
• Asymptomatic
▫ Ill-defined GI complaints 
most tolerate well
• Dysentery
▫ Diarrhea that contains visible
or microscopic blood
▫ Amebic colitis (several weeks)

 abdominal pain, tenderness, • Cutaneus amebiasis
diarrhea & bloody stools, ▫ Rare
weight loss, fever ▫ Involving abdominal wall,
 Acute necrotizing colitis face, uvula, vagina, penis
 Ameboma (granulation ▫ Occur from fisulous tract
tissue in colonic lumen)
Diagnosis
• Microscopy
▫ Examination of stools for cysts and trophozoites  ineffective
• Antigen detection
▫ A stool antigen detection  rapid, has improved sensitivity compared to
microscopy
▫ Detection of Gal/GalNAc-lectin in stool
• PCR
• Serology
▫ Indirect hemagglutination  anti amebic antibody 99% sensitive for
amebic liver abscess, 88% sensitive for amebic colitis
• Colonoscopy
▫ Amebic colitis  granular, friable, diffusely ulcerated mucosa, large
geographic ulcers, pseudomembranes
• Imaging
Treatment, prevention & control

• Interruption of the fecal-oral spread of the

infectious cyst stage  improved hygiene,
sanitation, water treatment
Giardiasis
• Ex: Giardia lamblia
• Asymptomatic infections  acute or chronic
diarrhea, malabsorptions, weight loss, failure to
thrive

• Description of the microorganism

▫ Flagellated
▫ Teardrop-shaped parasite
▫ 2 life forms  trophozoite & cyst
▫ Belongs to class Zoomastigophorea
• Growth requirement
▫ Anaerobic or microaerophylic environment &
exogenous cysteine
▫ Use glucosa as a major energy source  etanol,
acetate, carbondioxide
▫ Arginine dihydrolase path  reduce oxygen to
water by the action of NADH oxidase
Epidemiology & Predispotition factors

• Hypogammaglobulinemia
▫  prolonged diarrhea, malabsorption, severe histologic
change of intestine (nodular lymphoid hyperplasia)
• HIV & AIDS
Life cycle
Pathogenesis & Immunology
• Associated with intestinal mucosa but do not invade
 adherence is necessary to establish infection &
cause disease
▫  affect brush border & its enzyme
▫  stimulate inflammatory cytokine response 
secretion of fluid & electrolytes or damage to enterocytes

• Cellular & humoral mechanisms

▫ Proliferative response in Peyer’s patches
▫ CD4+ T cells critical to clearence
Clinical features
Chronic giardiasis & nutritional abnormalities

• Malaise, fatigue, diffuse abdominal cramps

• Stools which are usually greasy & foul smelling
• Weight loss
• May be periods of constipation
• Malabsorption of fat, vit B12, A, protein, D-
xylose, lactose, deficiency of lactase
• Failure to thrive in children
Laboratory diagnosis
• Parasite examination
▫ Stool examination  motile trophozoites & cysts
• Antigen detection assays
▫ ELISA & anti-giardia fluorescein labeled
monoclonal antibodies
• Duodenal sampling
• Serology & radiography
• Culture & sensitivity testing
Treatment
Prevention & control
• Proper disposal of human waste
• Provision of potable water in community
settings
• Fecal-oral hygiene
• Halogenation & chlorination may not sufficient
▫ Water processed by flocculation, sedimentation,
filtration, chlorination
Blastocystis
• Ex: Blastocystis hominis
• Morphology
▫ Vacuolar form
 Nuclei & mitochondria are seen in the peripheral rim of the cell surounding
the central vacuole (fx  metabolism & storage)
▫ Granular form
 Numerous small granules on the central vacuole
▫ Multivacuolar form
 Smaller than vacuolar forms, numerous vacuoles are seen
▫ Avacuolar form (rare)
▫ Cyst form
 Condensed cytoplasm contains many vacuoles & often large reserves of
glycogen & lipid
▫ Amoeboid form (rare)
Epidemiology
• Wide range of animal host (mammals, birds,
reptiles, arthropods)
• Distribution is world wide (developing countries
or communities with poor sanitary conditions)
• Travel particulary to tropical countries
Life cycle
Pathogenesis & Immunology
• Evidence supporting a causal role in GI disease
is based on the presence of Blastocystis as the
sole putative agent of disease

• Symptomatic patients  IgG responses

Clinical features
• GI infections
▫ Diarrhea, abdominal pain, cramps or discomfort,
nausea, flatulence, fever
▫ Rectal bleeding, faecal leukocytes, eosinophilia,
hepato & splenomegaly, cutaneus rashes & itching
• Extraintestinal infections
▫ Infection to synovial fluid  joint pain & swelling
• Symptomless infections
Laboratory diagnosis
• Microscopy
▫ Light microscopic faecal examination
▫ Wet mounts  refractile organisms, single vacuole with
4-6 dots clustered around the rim or within the body
• Culture
▫ From faecal material
• Immunological diagnosis
▫ Immunofluorescence assay (IFA) & enzyme linked
immunoabsorbent assay (ELISA)
• Other diagnosis procedure
▫ Endoscopy
Treatment, Prevention & control
• General anti-protozoal drugs (5-nitroimidazoles)
• Anti-bacterial compounds (ampicillin, penicillin,
streptomycin, gentamycin, colistin, ceftizoxime,
vancomycin)
• Metronidazole  persist  Cotrimoxazole

• Prevention
▫ Education to maintain personal & community hygiene
standards
▫ Improvement in community sanitary engineering 
prevent faecal contamination & ingestion
Nematoda related diarrhea
• Strongyloidiasis
• Ascariasis
• Hookworms
• Trichuriasis
Strongyloides Stercoralis
• This roundworm,2.5 mm in length, is endemic in
southern U.S. and common in tropicsand Asia.
• Clinical manifestation:
▫ Skin becomes red and pruritic after penetration by larvae, which
usually occurs on feet.
▫ Diarrhea,
▫ Vomiting
▫ Abdominal pain
▫ Cough and pneumonia after migration of larvae through lung
scan
▫ Peripheral eosinophilia may occur.
• Identification of larvae in stooldiagnostic.
Ascaris Lumbricoides
• Clinical manifestations:
 Can be asymptomatic
 Mild diarrhea
 Intermittent epigastric pain
 Anorexia
 Vomiting
• Diagnosed: by identifying whitish-brown Ascaris
worm,20–40 cm in length, or finding Ascaris
eggs on microscopic exam of stool is diagnostic.
Hookworm Infection
• Adult hookworms (N. americanus and A. duodenale)
• Clinical manifestations:
▫ Red, pruritic lesions on feetor between toes where larvae
penetrate.
▫ Diarrhea
▫ Vomiting
▫ Abdominal pain
▫ Anemia from GI blood loss
▫ Peripheral eosinophilia.
• Detecting hookworm eggs on stool smear is diagnostic.
Trichuris Trichiura
• T. trichiura,4-cm long whipworm, occurs most commonly
in tropical areas but is also found in subtropical areas (e.g.,
southern U.S.).
• Clinical manifestations:
▫ Most individuals are asymptomatic
▫ Diarrhea
▫ Tenesmus
▫ Weight loss
▫ Anemia
▫ Peripheral eosinophilia
• Diagnosed: by seeing eggs on microscopic stool examis
diagnostic.
Typhoid Fever
• Typhoid fever is an acute systemic infection caused
by Salmonella enterica serotype typhi or paratyphi
which is also known as Salmonella typhi
• Cause: Salmonella enterica serovar typhi(Salmonella
typhi)(Eberth’s bacillus), a Gram-negative bacillus.
• Synonim: Typhus abdominalis
• Clinical manifestation: Fever 1-2 weeks, abdominal
symptoms(pain, bloating,vomitus etc.), constipation,
diarrhea.
Salmonella sp.
Structure and physiology
- Bacillus 0.5 – 0.8 x 1 – 3
μm
- Gram negative
- No spore
- Fakultative anaerob
- Flagel peritrich  move (+)
- Stand in the freezing water
in a long period
- Stand in sodium deoxycholate,
brilliant green, sodium
tetrathionate
- sugar reactions:
fermentation of glucose (+),
mannosa (+)
not ferment lactose and
sucrose
- Oksidase test : negative,
nitrate positive, urease
negative
- TSIA : -/+, H2S (+), without
gas
 Epidemiology
The typhoid fever surveillance study
sites

Incidence of typhoid fever

♦ Strongly endemic
♦ Endemic
♦ Sporadic cases

http://www.who.int/bulletin/volumes/86/4/06-039818/en/
Antigen Structure
 Contaminated food of drinks Gastric acid
Pathogenesis
Bowel
1st systemic bacteriemia
lumen

Thoracic duct Mucosal defence

Regional Colonizatio
Lymphadenitis n

Invation to Peyer
Adhesion to mucose
Patch
Infection of RE system ,Liver, 2nd
Pathogenesis
Spleen Bacteriemia

Gall bladder Lung,

Myocard
Kidney, etc

Feces

Systemic
Reinfection in bowel mucose
manifestation

Bleeding,
Hyperplasia Peyer Patch Inflammation,
perforatio
erosion
n
Pathogenesis
A schematic diagram of a single Salmonella typhi cell showing
the locations of the H (flagellar), 0 (somatic), and Vi (K
envelope) antigens.
Typhoid Fever – Antigen
• Salmonella typhi has 3 kind of antigen:
▫ Flagella antigen (H): survive up to 60⁰C, to
alcohol and acid. IgG is the antibody against this
antigen
▫ Somatic antigen (O): located in outer membrane,
survive up to 100⁰C, to alcohol and acid. IgM is
the antibody against this antigen
▫ Vi antigen: located on O antigen, prevent
phagocytosis, survive up to 60⁰C, not resistant to
alcohol and acid
Pathophysiology Salmonella Typhi

survives the acidity of the stomach

invades the Peyer’s Patches of the intestinal wall

macrophages (Peyer’s Patches)

the bacteria is within the macrophages and survives

bacteria spreads via the lymphatics while inside the macrophages

Pathophysiology
access to Reticuloendothelial system, liver, spleen, gallbladder and
bone marrow

leads to perforation, bleeding

if left untreated, death is imminent

The 1st week
Fever, which will gradually rise and then settle
at around 39–40°C

Abdominal pain -Constipation or Diarrhoea-

Vomiting,

Dry cough

Dull headache -Delirium

Skin rash

Sign & symptoms

The 2nd week
If you don't receive treatment for typhoid
fever, you may enter a second stage during
which you become very ill and experience

Continuing high fever

Either diarrhea or severe constipation

Considerable weight loss

Extremely distended abdomen

Sign & symptoms

The 3rd week ( typhoid stage )

Become Delirious

Lie motionless and exhausted with

eyes half-closed in what's known
as the typhoid state

Life-threatening complications
often develop at this time.

Sign & symptoms

The 4th week (Improvement )

▫ If a person survives until the fourth week, their

symptoms will gradually improve

▫ Though weight loss and physical exhaustion can

continue for several months.

Sign & symptoms

Clinical Picture
• Fever • confusion, delirium
• Headache • psychosis
• malaise • convulsion
• myalgia • coated tongue
• nausea • bradicardia relative
• abdominal dis- comfort • tender abdomen
• constipation • hepatomegaly
• diarrhea • splenomegaly
• dry cough • rose spots
• epistaxis • erythmatous muco papular
lesion
Fever pattern : typhoid fever
• Typhus Inversus Pattern
▫ Lowest early in the morning
▫ Highest about 5.30 to 6.30 pm
▫ Can be found in typhoid fever tuberculosis
• Pulse Temperature dissosiation
▫ In normal temperature 37oC (99oF) pulse 80
beats/min
▫ Increased 9 beats/min every 1oF
▫ Relative bradicardia can be found in
 enteric/typhoid fever
 mycoplasma, malaria falciparum
• Devervescence : 3-7 days after treatment usually on 2nd
or 3rd weeks
Diagnosis
• History taking(Anamnesis): fever etc.
• Physical Examination: Relative bradycardia,
coated tongue, Hepatosplenomegali, bloating etc
• Supporting examination: blood
examination(hemoglobin, leukosit(leukopenia),
diff count, Lymphocytosis, Thrombocyte), C-
reactive protein(CRP), Widal, Gall Culture,
Tubex test(IgM S.typhi), urine/stool
examination(culture for Salmonella- Shigella),
Bone marrow culture for Salmonella-Shigella,
Polymerase chain reaction.
Treatment
• Non Pharmacologic : Bed rest, Nutrition
• Pharmacologic
• Symptomatic
• Antibiotic :
Ampicillin/Amoxicillin 2x750 or 3x500 mg
Chloramphenicol 4x500mg
• Cephalosporin : Ceftriaxone 3-4 g/days
• Fluoroquinolones :
▫ Ciprofloxaxin 2x500 mg
▫ Ofloxacin 2x400 mg
▫ Pefloxacin 1x400 mg
Management of intestinal complication of typhoid
fever

• Lower GI hemorrhage: Intravenous Antibiotic,

Blood Transfusion, Fresh Frozen Plasma,
Hemostatic(Tranexamic Acid, Traditional
Chinese Medicine: Stobled/Yunan baiyo),
cytoprotectors: sucralfate, rebamipide.
• Perforation/peritonitis: surgery/laparotomy, Iv
Antibiotic
• Intestinal ulcers/inflammation: Antibiotic,
cytoprotectors: sucralfate, rebamipide.
Complications
• Intestinal complication intestinal perforation
gastrointestinal hemorrhage hepatiitis, pancreatitis,
paralytic ileus
• Extraintestinal Cardiovascular : shock, myocarditis
• Neuropsychiatric : encephalopaty, delirium psychosis
• Respiratory : bronchitis, pneumonia, pleuritis
• Hematology : anemia, DIC
• Kidney : glemerulonephritis, pyelonephritis
• Others : osteomyelitis, focal abscess
Complications
• Septicemia
• Septic shock
• Toxic state
• Abdominal: Lower Gastrointestinal Bleeding (hematochezia),
perforation(0.8-18%; 86% located in ileum) and peritonitis,
hepatitis.
• Genitourinary: retention urine, glomerulonephritis.
• Cardiovascular:ECG changes, myocarditis etc.
• Respiratory:pneumonia, bronchitis.
• Neuropsychiatric: obtundation, delirium, coma, depression etc.
• Haematological: DIC, anemia, etc.
• Other: Focal abscesses of brain, liver etc.
• Metabolic acidosis, relapse.
Carrier State
• Exist of S. typhi in feces or urine without clinical
manifestation 1 year after recovery from typhoid
fever
• S. typhi still be found in feces of urine 2 or 3
months after recovery in 16% patients
• Impairment of host defence mechanism, gall and
kidney stone, chronic gall and kidney infection
contribute in pathogenesis of carrier state
Carrier State
• Diagnosis of carrier state : feces and urine
culture, Vi antibody
• Treatment :
• Without gall stone : Ampicillin, Amoxicillin,
Cotrimoxazole
• With gall stone : Cholecystectomi and treatment
with Ciprofloxacin or Norfloxacin
• With Schistosomiasis : Eradication of
schistosomiasis before treatment of carier state
Prevention
• Avoid risky food or drinks
▫ • Hand washing
▫ • Vaccination
▫ • Detection of carrier state in food handler
DD
• Yersinia enterocolitis
• Mycobacteria tuberculosis
• Entamoeba histolytica
• Campylobacter
• Salmonella paratyphi and others
• Aeromonas hydrophilia
• Histoplasma capsulatrum
• Cytomegalovirus(in AIDS pts)
• Behcet’s disease
• Vasculitis
• Crohn’s disease
• NSAID enterocolopathy
References
• Dalley, Arthur F. Keith L Moore. Clinically Oriented Anatomy.
5th edition. Lippincott Williams & Wilcins; 2006
• Fauci. Braunwald. Dkk. Harrison’s Principles of Internal
Medicine. 17th edition. United State: The McGraw-Hills; 2008
• L. Mescher, Anthony. Junquera’s Basic Histology Text and
Atlas. 20th edition. United State: The McGraw-Hills; 2010
• Sherwood,Lauralee. Fisiologi Manusia dari Sel ke Sistem.
Cetakan pertama edisi 2. Jakarta: EGC; 2001
• Gillespie, S. Richard D Pearson. Principles and Practice of
Clinical Parasitology. John Wiley & Sons, LTD; 2001