prof.barmawi.....kuliah 7 thyphoid ,pancreatitis fever 1

8/12/2019 Prof.barmawi.....KULIAH 7 THYPHOID ,Pancreatitis Fever 1

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Typho id Fever

pancreat i t is


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Typhoid Fever

Typhoid fever is a systemic infection with the

bacterium Salmonella enterica serotype

typhi.

A subset of Salmonel laserotypes thatincludes S. typhiand S. paratyphicauses

enteric (typhoid) fever and is restricted to

growth in human hosts.

Clinically S. typhi > S. paratyphi


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Salmonella

Genus enterobacteriaceae

" S. enter i t id is"

including var. t yph imur ium,paratyphi& bongor i

200 serovarian

S. chol erae-su is, 1 serovar

S. typh i, 1 serovar

gram-negative bacilli

Motil & pathogenic

Salmonel lacan be further divided into serovars

based on the detection of three major antigenicdeterminants:

the somatic O antigen

[lipopolysaccharide (LPS) cell-wall

components]

the surface Vi antigen (restricted to S.

typhiand S. paratyph iC), the flagellar H antigen.


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Nomenklatur


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Epidemiology

Endemic in developing contries

Incubation period : 3 d3 m (1-3 wk)

Transmission : most cases of disease result from

ingestion of contaminated food or water

anal-oral transmission health care workers


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Pathogenesis

The bacteria traverse the gastrointestinal tract, including the acidic environment of the

stomach, to colonize the small intestines. Salmonellae cross the intestinal barrier, where

phagocytosis by macrophages results in their dissemination throughout the

reticuloendothelial system.

Once salmonellae reach the small intestine, the bacteria resist a variety of innate immune

factors before penetrating the mucus layer. The organisms enter the intestines through

phagocytic microfold or M cells overlying the Peyer's patches. Salmonellae (S. typhior S. paratyphi) undergo phagocytosis by macrophages after crossing

the epithelial layer of the small intestine.

Once phagocytosed, the bacteria are protected from PMNs) the complement system, and

antibodies.

After phagocytosis, salmonellae disseminate throughout the body in macrophages via the

lymphatics and colonize reticuloendothelial tissues (liver, spleen, lymph nodes, and bone

marrow).

Signs and symptoms, including fever and abdominal pain, probably result from secretion of

cytokines by macrophages when a critical number of organisms have replicated..


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Patofisiologi


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Rose spot


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Relative bradicardia


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Laboratorium


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Widal Test


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Treatment


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Complications

Complications occur in 10 to 15 percent of patients

Gastrointestinal bleeding, intestinal perforation, and

typhoid encephalopathy are the most important.

Gastrointestinal bleeding is the most common,

occurring in up to 10 percent of patients. It results

from erosion of a necrotic Peyers patch through the

wall of an enteric vessel.


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CarrierTyphoid


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Typhoid FeverPrevention Safe water supplies sanitary disposal of humanfeces and hygienic food handle are essentialsteps to Typhoid control. Sanitation improvements demand high publicinvestments. For this reason achieving realgains in sanitation coverage has been achallenge in developing countries. Whether a rapid reduction in the incidence ofTyphoid could be brought about by mass

vaccination has been a matter of discussion. Thecurrently licensed Vi polysaccharide vaccinesare not very effective. In Brazil vaccines havenot been used so far.


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Acute Pancreatitis


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Associated Structures of theGall Bladder and Pancreas


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Acute Pancreatitis

Epidemiology Second most common principal

inpatient GI diagnosis aftercholelithiasis and acute

cholecystitis Unreliable data due to misdiagnosis Estimated yearly incidence of 5-

40/100,000

1998 data from the U.S. aboutpancreatic diseases 327,000 inpatient stays 78,000 outpatient hospital visits 195,000 ER visits 531,000 office visits


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Natural History

80% of cases are mild

20% are severe with organ failure andlocal complications

Estimated 25-33% mortality Overall mortality estimates range from 2%

to 10%

Half of death occur within the first week,perhaps 25% to 33% of deaths occur withinthe first 48 hours

Obese patients have higher rates of localcomplications, respiratory failure, severeacute pancreatitis and death from sterile

necrosis than non-obese patients


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Definition

Acute inflammation of thepancreas

Varying degree of regionaltissue involvement and remoteorgan systems

Classified as acute unless thereis evidence of chronicpancreatitis, otherwise

considered as exacerbation of


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Pathology

Initial injury to peripheral acinarcells, fat necrosis and autodigestion

Interstitial (edematous) pancreatitis: Interstitial edema associated with

inflammatory cells in the parenchyma

Parenchymal necrosis is microscopic

Necrotizing pancreatitis Focal macroscopic or diffuse necrosis

Hemorrhage, vascular thrombosis

Involvement of the main pancreatic duct


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Pathogenesis of AcutePancreatitis

Trypsinogen to trypsinconversion in acinar cells

overwhelms neutralizationmechanisms

Proenzymes (trypsinogen,

elastase, phospholipase A2(PLA2) and carboxypeptidase)are activated by trypsin

Activation of complement and


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Etiologies of AcutePancreatitis

Obstructive

Toxic

Metabolic Infectious

Vascular

Trauma

Iatrogenic

Hereditary

Controversial etiologies


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Toxic and MetabolicEtiologies

Toxic

Ethanol

Methyl alcohol Scorpion venom (hyperstimulation of

pancreas)

Organophosphate insecticides

(hyperstimulation of pancreas) Drugs

Metabolic

Hypertriglyceridemia

Hypercalcemia


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Other Causes

Cardiovascular

Small vessel vasculitis

Emboli to pancreatic vessels Hypotension

Blunt and penetrating

abdominal traumas Iatrogenic

ERCP

Surgery


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Gallstone/BiliaryPancreatitis

40% of all cases of AP

Risk of AP due to existing

gallstones is greater in men, butoverall incidence is lower asgallstones are more common in

women Small stones (< 5 mm) are more

likely to cause pancreatitis


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Biliary Sludge

Viscous suspension of gallbladderbile that may contain tiny stones (< 3mm)

Usually composed of cholesterolmonohydrate crystals, but alsooccurs with ceftriaxone-bilecomplexes

Appears as a mobile, low-amplitudeecho without shadow

Biliary sludge often develops inacute pancreatitis


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Alcohol

Causes 30% of cases

Most but not all patients also havesome degree of underlying chronicpancreatitis

Proposed mechanisms: Sphincter of Oddi relaxation & duodenal

reflux

Increased pancreatic duct permeability

Sudden release of pancreatic enzymeswith inappropriate activation

Increased protein concentration in

pancreatic juice leading to obstruction


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Third most common identifiablecause of AP

Serum triglycerides > 1000mg/dL

Median serum TG concentration

~ 3-4K Mechanism?

Possibly, release of free fatty

acids may cause pancreatic acinar


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Associated conditions in adults

Diabetes mellitus

Alcohol abuse (chicken or theegg?)

Obesity

Hypothyroidism Pregnancy

Estrogen therapy

Types I & V hyperlipoproteinemia


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Hypercalcemia

Rare, proposed mechanism is due todeposition of calcium in the pancreaticduct with activation of trypsinogen in thepancreatic parenchyma

Chronic hypercalcemia less likely toinduce pancreatitis than acute increases(animal data)

Hyperparathyroidism causes < 0.5% of allcases of acute pancreatitis

Incidence of acute pancreatitis inhyperparathyroidism is reportedly 02%-1.5%

Rarely after metastatic cancer with boneinvolvement, TPN, sarcoidosis, vitamin D

toxicity and following parenteral


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Tumors

Probably cause AP due toobstruction of the pancreatic duct

Usually in older patients Most common with intraductal

papillary mucinous neoplasm/tumor(IPMN/IPMT) of the pancreas

Also possible with ampullaryneoplasms

Less commonly due to pancreatic

adenocarcinoma


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DrugsGeneralConsiderations

Over 80 drugs implicated based onunconvincing anecdotal reports

Usually mild and self-limited afterstopping drug

Reliable causative etiology requires:

Exclusion of other etiologies

Appropriate interval (usually 4-8 weeks)since initiation of therapy

Clear mechanism of drug-inducedpancreatitis

Reproducible recurrence of pancreatitis


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Drugs Implicated

-Methyldopa Mesalamine Cimetidine

Cytosinearabinoside Dexamethasone Ethinylestradiol/

lynestrenol

Furosemide Isoniazid 6-Meraptopurine Metronidazole

Norethindrone/mestranol

Pentamidine Perindopril Pravastatin

Procainamide Stibogluconate Sulfamethizole Sulfasalazine Sulindac Tetracycline TMP/SMX Didanosine Valproic acid


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Potential Mechanisms(Contd)

Accumulation of toxicmetabolites

Onset typically occurs afterseveral months

E.g. valproic acid, didanosine

Hypertriglyceridemia Thiazides, tamoxifen, isotretinoin

Intrinsic toxicity

Pancreatitis can occur with


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Diagnosis of AP

Clinical findings

Laboratory findings

Radiological findings


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Clinical Findings

Usually acute onset of severe pain

Epigastric, upper quadrants

Radiation to back and chest (DDxmyocardial ischemia)

Nausea, vomiting, hematemesis

Bowel obstruction

Fever, tachypnea, shock

Ecchymoses on the flanks (Turners

sign)

Periumbilical ecch mosis Cullens


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Laboratory findings

2-3 fold elevations of pancreatic enzymesamylase and/or lipase

Amylase

Cheap, fast and widely available Not 100% sensitive or specific (normal values in

mild attacks, in the setting of chronicpancreatitis or even with fatal pancreatitis havebeen reported)

False positive (as far as AP Dx is concerned)with:

Macroamylasemia (e.g. IG-bound amylase notcleared by kidneys)

Parotitis (can also be EtOH induced, look forhamster cheeks!)

Salpingitis/ectopic pregnancy Bowel obstruction and erforation


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Lipase

Sensitivity similar to amylase(85%-100%)

Probably more specific (allpancreatic except a smallamount of gastric lipase)

Usually remains elevated longerthan amylase

False positive values in: Renal insufficiency

Macrolipasemia


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Other PancreaticEnzymes

Generally speaking, no significant clinicaladvantage over routine tests due to: Similar dynamics Expense

Unavailability Phospholipase A2 Trypsin Caboxypeptidase A

Colipase Elastase Ribonuclease Trypsin Activation Peptide (TAP)


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Other Lab Findings

Nonspecific findings include

Leukocytosis

LFT abnormalities CRP and other acute reactants

Serum triglycerides

Azotemia Hyperglycemia


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Radiological Findings

Plain Films: Localized segment of small intestine

(sentinel loop)

Generalize ileus Calcifications (stones, or pancreas with

chronic calcific pancreatitis)

Pneumobilia following stone passage

and/or bilioenteric fistula formation Severe ascites

Retroperitoneal gas (pancreaticabscess)

30% with CXR abnormalities (elevatedhemidiaphragm, pleural effusion, basal


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CT and US

Cross-sectional imaging withmore specific pancreaticchanges (i.v. contrast is neededfor detecting necrosis andtumors)

US may show biliary dilation,

stones, pancreaticcalcifications, hypoechoicappearance of the pancreaswith edema, pseudocysts and

eri ancreatic fluid collections


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Differential Diagnosis

Biliary pain and acute cholecystitis

Epigastric distress syndrome/non-

ulcer dyspepsia Peptic ulcer disease and perforated

hollow viscus

Small bowel obstruction

Inferior myocardial infarction

Aortic dissection

Ruptured ectopic pregnancy

Acute a endicitis


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Range of Severity

Mild Minimal or no organ dysfunction

Full recovery withoutcomplications

Severe Local complications

Organ failure

death


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Predictors of Severity

Ransons Score 2: Mortality

2.5%*

Ransons Score 3: Mortality62%*

Limitations of Ransons Score:

Cumbersome Takes 48 hours to compute

Not validated beyond 48 hours

Cutoff of 3 has sensitivity of 40%-* Obtained within the first 48 hours


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Atl t C it i f


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Atlanta Criteria forSevere AP

ORGAN FAILUREShock SBP < 90 mm Hg

Pulmonary insufficiency pO2 60 mm Hg

Renal failure Serum creatinine > 2 mg/dL

GI bleeding >500 mL/24 hr

LOCAL COMPLICATIONSNecrosis

Abscess

PseudocystUNFAVORABLE EARLY PROGNOSTIC SIGNS 3 Ransons criteria

APACHE II score 8


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Approach to Patient

Triage Prognosis

Placement

Etiology Could affect the acute management

Supportive care I.v. fluid resuscitation

Nutritional support

Analgesia


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Further care

Observation for early detectionof potential complications

Treatment of complication Nutritional support (10% rate of

TPN line infections in patients

with severe pancreatitis)


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Nutritional Support

TPN disadvantages Expensive

High complication rate

Generally associated with highermorbidity and longer lengths of staythan enteral feeding via nasoenterictubes

In mild to moderate AP, enteral feedingwas started within 48 hours ofadmission and was associated withfaster improvement and shorter LOSthan TPN

In severe/necrotizing pancreatitis, LOS,


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prof.barmawi.....kuliah 7 thyphoid ,pancreatitis fever 1

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