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Subject: Clinical Pathologic Conference Date: June 25, 2008

Topic: Case 1 No. of Pages: 5


Transcriber: lucky Editor: Reyia

UPON EVISCERATION:
 SEGMENT OF ILEUM AND CECUM
o Approx 1.5Liters of clotted blood

The pathologist received a body of a 24- year old male, born in Leyte, whose chief complaint was fever, a non-
specific sign and symptom.

Typhoid Bacilli and Water Contamination

Stomach
Ability to penetrate the epithelial cells

Rapidly taken up by macrophages

Small Intestine

Mesenteric Lymph Nodes

Thoracic Duct

Carried by macrophages

Bloodstream

End of Incubation Period

 Transient or primary Bacteremia


o Brief bacteremic period (not dependent on the
amount of bacilli present)
 CMI takes longer to develop

 Non specific signs and symptoms


o May mimic most of the infectious diseases
o Leukocytopenia

Filtered by fixed macrophages in the reticuloendothelial system (RES)


o Liver, Spleen

Secondary Bacteremic Phase

 Continuous multiplication of typhoid bacilli in macrophages in the


o Liver, Spleen, Bone Marrow

• Disease of the RES Aggregates of mononuclear


• CMI mounts a strong cells forming granulomatous
inflammatory response lesions

1
Brain Meningoencephalitis seizure
Typhoid Nodule
Adrenal
1. Less distinct granuloma
2. More Pronounce necrosis
3. Erythrophagocytosis Pancreas

Spleen Splenomegaly

Mesenteric lymph nodes, colon and ileum

Ileum

Hyperplasia of Peyers
Patches in the Ileum

Granulomatous lesions may necrotize secondary to


occlusion of smaller vessels (microthrombi formation)

Necrotizing lesions progressively coalesce

Ulceration in the intestinal wall (ileum)

Concomitant Schistosoma infection


• Liver, lungs, pancreas, colon and mesocolic lymph nodes
• Schistosoma ova
o Delayed type of hypersensitivity reaction
o Granuloma formation surrounding the schistosoma
ova which later on replaced by fibrosis

Overloading of the Reticuloendothelial System

Susceptibility to Salmonela Septicemia

• Hypotension
• Bradycardia not improved by fluid challenge

Septic Shock

Day 10: Death

FINAL ANATOMIC DIAGNOSIS


I. SALMONELLA SEPTICEMIA
A. MULTIPLE TYPHOID NODULES
A. EROSION , ULCERATION AND HEMORRHAGES , ILEUM
B. LIVER
C. BRAIN
D. KIDNEYS
E. COLON
F. PANCREAS
G. ADRENALS
H. MESOCOLIC LYMPH NODES

B. POST MORTEM CULTURE OF:


• ILEAL ULCERS
• BILE OF THE GALLBLADDER
2
• SPLENIC PULP
(+) POSITIVE FOR SALMONELLA TYPHI GROWTH
C. CHRONIC GRANULOMATOUS INFLAMMATION AND SCHISTOSOMA OVA INVOLVING THE:
• LIVER
• PANCREAS
• COLON
• MESOCOLON LYMPH NODES
(+) CONSISTENT WITH SCHISTOSOMA JAPONICUM INFECTION

D. REACTIVE SPLENITIS

II. BRONCHOPNEUMONIA , BILATERAL

III. HEPATOMEGALY (1,750 GRAMS)

CAUSE OF DEATH: SEPTIC SHOCK SECONDARY TO SEVERE SALMONELLA TYPHI BACTEREMIA

Etiologic agent: Salmonella enterica serovar typhi


• Exclusive human pathogen
• Gram negative flagellated bacilli
• Non-sporulating facultative anaerobe
• Reduces nitrate to nitrite
• Synthesizes peritrichous flagella when motile
• Has somatic O, flagellar H, envelope K and surface virulence (Vi) antigens and LPS endotoxin

Pathophysiology and mode of infection:

Ingestion of S. typhi by host Invades through gut Multiplies within mononuclear phagocytic cells

Stool, urine
Colonizes: Inflammation and
• Liver diarrhea
• Spleen
• Lymph nodes
Infect other hosts • Peyer’s Patches
Bile ducts Ulcers,
peritonitis

In receptor- mediated
Gallbladder phagocytosis In gut epithelium:
Submucosa: Macrophage Bacteria- mediated
endocytosis (BME)

Bile ducts Enters blood stream Apoptosis

Symptoms and diagnosis:


• First symptoms include: loss of appetite, fever, headache, joint pain, sore throat, constipation (or, less
commonly, diarrhea), and abdominal pain and tenderness.

• As the illness progresses, fever remains high, and the person may become delirious. Sustained fever is often
accompanied by a slow heartbeat and extreme exhaustion.

• During the second week and last 2 to 5 days: 10% of infected people get clusters of small, pink spots on the
chest and abdomen (Rose spots from typhoid fever)

• Intestinal bleeding or perforation occurs in 3 to 5% of infected people (ulcerated peyer’s patches)

• Pneumonia may develop

• Infection of the gallbladder and liver

• At the final stage, a blood infection (bacteremia) occasionally leads to infection of bones (osteomyelitis), heart
valves (endocarditis), kidneys (glomerulitis), the genitourinary tract and tissues covering the brain and spinal
cord (meningitis).

• Infection of muscles may lead to abscesses (collections of pus).

3
• Although the history and symptoms of illness may suggest typhoid fever, the diagnosis must be confirmed by
identifying the bacteria in cultures of blood, stool, urine, or other body fluids or tissues.

1. symptoms begin gradually 8 to 14 days after infection. The brassy, nonproductive cough is common.
Nosebleed may occur.
2. This Diarrhea may continue, although some people become constipated. In about 10% of infected people,
clusters of small, pink spots appear on the chest and abdomen during the second week and last 2 to 5
days. After 2 weeks, intestinal bleeding or perforation occurs in 3 to 5% of infected people.
3. Pneumonia usually results from a pneumococcal infection, although typhoid bacteria can also cause
pneumonia.

POSSIBLE SPECIMENS TO BE SUBMITTED FOR CULTURE (BUS)

1. BLOOD-1ST week of infection


2. URINE- 2ND week of infection
3. STOOL- 3RD week of infection

Chronic carrier state:


• 1-4% of untreated patients become chronic carriers.
• Stool carriage is more frequent in people with preexisting biliary abnormalities and these people have a greater
incidence of cholecystitis.
• Greater risk for carcinoma of the gallbladder
• 6-fold increase in the risk of death due to hepatobiliary cancer.
• chronic carriers: defined as individuals who excrete Salmonella for more than 1 year.
• Some individuals may continue to excrete the bacterium for decades.
• biliary abnormalities perhaps because S enterica survives in gallstones,
• hepatobiliary cancer. This may be due to chronic inflammation caused by the bacterium.

DISCUSSION

CASE 1: Salmonella Septicemia


Salmonella typhi
- Flagellated, gram negative bacteria

- Causes Self limited food borne and water borne gastroenteritis or typhoid fever

- Primarily affects the ileum and colon

Morphology and histology:


- Generating blunted villi

- Vascular congestion

- Mononuclear inflammation

- Peyer patchers inv: swelling, congestion, ulceration with linear ulcers, become sharply
delineated, plateau like elevations upto 8 cm in diameter, enlargement of draining mesenteric
lymph nodes

- Shedding of the mucosa and swollen lymph nodes  oval ulcers along the axis of the ileum

Microscopic findings:
- Macrophages containing bacteria

- RBCs

- Nuclear debris

Gross findings:
a. Spleen

- Enlarged, soft and bulging with uniformly pale red pulp, obliterated follicular markings and
prominent sinus histiocytosis and reticuloendothelial proliferation

b. Liver

- Small, randomly scattered foci of parenchymal necrosis

- Hepatocytes are replaced by a phagocytic mononuclear aggregate  typhoid nodules (1.LESS


DISTINCT GRANULOMA 2. MORE PRONOUNCED NECROSIS 3. ERYTHROPHAGOCYTOSIS)

Typhoid fever
- Marked by fever and systemic symptoms ( S.typhi)
4
- Protracted disease that is associated with

- 1st week: bacteremia, fever and chills

- 2nd week: Widespread mononuclear phagocyte involvement with rash, abdominal pain and
prostration

- 3rd week: ulceration of peyer patches with intestinal bleeding and shock

Pathogenesis:
- Salmonella invades intestinal epithelial cells, macrophages

- Invasion is controlled by invasion genes that are induced by low tension found in the gut

- Genes encode proteins that internalize the bacterium

- Intramacrophage growth  impt. In pathogenecity, mediated by bact. Genes that are induced
by the acid ph within the macrophage pahgolysosome

- Enteric nervous system  critical regulator of fluid secretion in the normal gut

- Neural reflex pathways  increase epithelial fluid secretion in response to enteric pathogens

- Bacteremia and systemic dissemination  cause proliferation of phagocytes with enlargement


of reticuloendothelial and lymphoid tissues

Pathophysiology:
• After ingestion by the host, S typhi invades through the gut and multiplies within the
mononuclear phagocytic cells in the liver, spleen, lymph nodes, and Peyer patches

• After successfully passing through the stomach, any Salmonella subspecies may be
phagocytized by the gut's intraluminal dendritic cells, causing inflammation that leads to
diarrhea. Only the subspecies S enterica causes severe disease in the rest of the body. Its
specialized fimbriae adhere to the epithelium that overlies Peyer patches.

• They are the primary mechanism for sampling antigens in the gut and initiating response. S
enterica enters them via 1 of 3 pathways.

• S enterica may convert normally nonphagocytic epithelial cells into bacterially-mediated


endocytosis (BME).

• In BME, Salmonella uses a type III secretion system—macromolecular channels

• Salmonella insert into eukaryotic cells and intracellular membranes to inject virulence
proteins—to inject proteins SipA and SipC into the epithelial cell. These disrupt the normal
brush border and force the cell to form membrane ruffles. The ruffles engulf the bacilli and
create vesicles that carry them across the epithelial cell cytoplasm and the basolateral
membrane.

• In the submucosa, Salmonella enters macrophages via bacteria-triggered pinocytosis or via


macrophage receptor–mediated phagocytosis. The intravacuolar environment activates the
PhoP/PhoQ regulon, leading to modification of protein and lipopolysaccharide elements of the
bacterial inner and outer membranes. Thus, Salmonella resists lysis and decreases host
proinflammatory signaling. The bacterium also produces homocysteine to inactivate nitric
oxide and enzymes against other microbicides. Finally, with the Vi antigen, a polysaccharide
capsule, S typhi and S paratyphi further protect themselves from lysis within the macrophage
and from neutrophils and complement without.

• In these havens, it multiplies until some critical density is reached. It causes the apoptosis in
the macrophages and enters the bloodstream to attack the rest of the body. At this stage, the
Vi antigen comes into play. It forms a capsule to protect the bacterium from complement and
from phagocytic immune cells.

• From blood or from the liver via bile ducts, it infects the gallbladder and reenters the
gastrointestinal tract in the bile, spreading to other hosts via stool.

• After primary intestinal infection, further seeding of the Peyer patches occurs through infected
bile. They may become hyperplastic and necrotic with infiltration of mononuclear cells and
neutrophils, forming ulcers that may hemorrhage through eroded blood vessels or perforate
the bowel wall, causing peritonitis.

Chronic Schistosomiasis
 Cercarial penetration to maturation of adult worms
 Active egg deposition
 Immunologic process resulting from cumulative deposition of eggs

5
Miracidium hatches out from excreted egg → miracidia infect snails → many cercariae released from
infected snails → people infected by contact with cercariae in water → cercariae enters skin & lose
their tail to become schistosomulae → schistosomulae migrate through tissues, penetrate a blood
vessel → brought to right heart & lungs → they squeeze thru pulmonary capillaries into the systemic
circulation → portal vessels → schistosomule mature in the hepatic portal venules & form pairs →
worms migrate against portal blood flow & deposit eggs into the mesenteric, vesical and pelvic
venules
Pathophysio:
- Granuloma formation and hepatic fibrosis
- Assoc. with dominant Th2 response with persistence of Th1 helper cells

Septic Shock:
Septic shock - due to bacterial toxins thus widespread vasodilation
- no loss of intravascular volume
- high vasodilation
- pooling of venous blood
- low cardiac output