Organophosphates Intoxication (Pesticides)

Organophosphates Intoxication

Pesticides can be defined as any substance or mixture of substances

intended for preventing, destroying, repelling, or mitigating pests.

Pests can be insects, rodents, weeds, and a host of other unwanted

Organisms

The four major classes (and their

target pests) are those of insecticides (insects), herbicides (weeds) fungicides (fungi, molds), and rodenticides (rodents), but there are

also acaricides (mites), molluscides (snails, other mollusks), miticides

(mites), larvicides (larvae), and pediculocides (lice). In addition,

for regulatory purposes, plant growth regulators, repellants, and

attractants (pheromones) often also fall in this broad classification of

chemicals.

For example, among insecticides, one can find organophosphorus

compounds, carbamates, organochlorines, pyrethroids, and

many other chemicals. Even within each of these subclasses, significant

differences can exist, as is the case, for example, of organochlorine

compounds such as DDT, aldrin, or chlordecone. Thus, detailed

knowledge of the toxicological characteristics of each chemical

is needed to properly evaluate their potential risks for nontarget

species.

Exposure to pesticides can occur via the oral or dermal routes or by

inhalation. From a quantitative perspective, oral exposure lies on the

extremes of a hypothetical dose–response curve. High oral doses,

leading to severe poisoning and death, are achieved as a result of pesticide

ingestion for suicidal intents, or of accidental ingestion, commonly

due to storage of pesticides in improper containers. Chronic

low doses on the other hand, are consumed by the general population

as pesticide residues in food, or as contaminants in drinking.

Workers involved in the production, transport, mixing

and loading, and application of pesticides, as well as in harvesting of

pesticide-sprayed crops, are at highest risk for pesticide exposure.

The dermal route is thought in this case to offer the greatest potential

for exposure, with a minor contribution of the respiratory route when

aerosols or aerial spraying are used

.

In the occupational setting, dermal

exposure during normal handling or application of pesticides,

or in case of accidental spillings, occurs in body areas not covered

by protective clothing, such as the face or the hands.

In the general population and in occupationally exposed

workers, a primary concern relates to a possible association between

pesticide exposure and increased risk of cáncer.

The World Health Organization

(WHO) estimated that there are around three million hospital

admissions for pesticide poisoning each year, that result in

around 220,000 deaths (WHO, 1990).

Indeed, among the 74 active ingredients

listed in Class 1A (Extremely hazardous) and Class 1B (Highly hazardous),

48 (65%) are insecticides, in particular organophosphates

Rodenticides are also highly toxic to rats, but do not

present the same hazard to humans. Indeed,warfarin, one of the most

widely used rodenticides, is the same chemical used as an effective

“blood thinner” (anticoagulant) for prevention of stroke and other

blood clot related conditions. Herbicides, again as a class, have generally

moderate to low acute toxicity, one exception being paraquat

(which has a low dermal toxicity but causes fatal effects when ingested).

Fungicides vary in their acute toxicity, but this is usually

low.

Reports of human poisonings worldwide confirm this analysis.

In Costa Rica between 1980 and 1986, 3330 individuals were

hospitalized for pesticide poisoning, and 429 died. Cholinesterase

inhibitors (organophosphates and carbamates) caused 63% of hospitalizations

and 36% of deaths, while paraquat accounted for 24%

of hospitalizations and 60% of deaths. Cholinesterase inhibitors

also caused more than 70% of occupational accidents.

Organophosphates, carbamates and paraquat were again involved in

the majority of cases

Insecticides play a most relevant role in the control of insect pests,

particularly in developing countries. All of the chemical insecticides

in use today are neurotoxicants, and act by poisoning the

nervous systems of the target organisms (Table 22-8).

The German chemist Gerhard Schrader is credited for

the discovery of the general chemical structure of anticholinesterase

OP compounds, and for the synthesis of the first commercialized OP

insecticide [Bladan, containing TEPP (tetraethyl pyrophosphate) as

the active ingredient], and for one of the most known, parathion, in

Where X is the so-called “leaving group,” that is displaced when

the OP phosphorylates acetylcholinesterase (AChE), and is the most

sensitive to hydrolysis;R1 andR2 are most commonly alkoxy groups

(i.e., OCH3 or OC2H5), though other chemical substitutes are also

possible; either an oxygen or a sulfur (in this case the compound

should be defined as a phosphorothioate) are also attached to the

phosphorus with a double bond. Based on chemical differences,

OPs can be divided into several subclasses, which include phosphates,

phosphorothioates, phosphoramidates, phosphonates, and

others (Chambers et al., 2001).

For all compounds

that contain a sulfur bound to the phosphorus, a metabolic

bioactivation is necessary for their biological activity to be manifest,

as only compounds with a P=O moiety are effective inhibitors

of AChE.

This bioactivation consists in an oxidative desulfuration

mediated, mostly but not exclusively in the liver, by cytochromeP450 enzymes (CYPs), and leading to the formation of an “oxon,”

or oxygen analog of the parent insecticide (Fig. 22-2). Though this

reaction has been known for several decades, the exact CYP isoforms

involved have only been recently investigated, and available

data suggest that the overall picture is quite complex.

For example, diazinon is activated

by human hepatic CYP2C19, whereas parathion is activated

primarily by CYP3A4/5 and CYP2C8, and chlorpyrifos by CYP2B6. Of relevance to insecticidal OPs is thioether oxidation

(formation of a sulfoxide, S=O, followed by the formation of

a sulfone, O=S=O) which occurs in the leaving group moiety, and

is also catalyzed by CYPs. For example, in case of the OP disulfoton,

the sulfoxide and the sulfone are more potent inhibitors of

AChE than the parent compound. Noncatalytic hydrolysis of OPs also occurs when these compounds

phosphorylate serine esterases classified as B-esterases, that

are inhibited by OPs but cannot catalytically hydrolyze them. Examples

are the carboxylesterases (CarE) and butyrylcholinesterase

(BuChE), in addition to the OP target, AChE. CarE also performs

a catalytic hydrolysis of the carboxylic esters of malathion, and is

believed to be a major determinant of its low toxicity in mammals

Signs and Symptoms of Toxicity and Mechanism of Action OP

insecticides have high acute toxicity, with oral LD50 values in rat

often below 50 mg/kg, though for some widely used compounds

(e.g., chlorpyrifos, diazinon) toxicity is somewhat lower, due to effective

detoxication. One exception is malathion, which has an oral

LD50 in rat of >1 g/kg, due, as said, to rapid detoxication by CarE

For several OPs acute dermal toxicity is also high, with some exceptions

being azinphosmethyl and malathion (Murphy, 1986). The

primary target for OPs is AChE, a B-esterase whose physiological

role is that of hydrolyzing acetylcholine, a major neurotransmitter in

the central and peripheral (autonomic and motor-somatic) nervous

systems. Acetylcholine released from cholinergic nerve terminals is

disposed of solely through hydrolysis by AChE. In fact, in contrast

to other neurotransmitters (e.g., norepinephrine), it is choline, the

product of acetylcholine hydrolysis by AChE, that is taken up by

the presynaptic terminal. Hence, inhibition of AChE by OPs causes

accumulation of acetylcholine at cholinergic synapses, with overstimulation

of cholinergic receptors of the muscarinic and nicotinic

type. As these receptors are localized in most organs of the body, a

“cholinergic syndrome” ensues, which includes increased sweating

and salivation, profound bronchial secretion, bronchoconstriction,

miosis, increased gastrointestinal motility, diarrhea, tremors, muscular

twitching, and various central nervous system effects. When death occurs, this is believed to be due to respiratory

failure due to inhibition of respiratory centers in the brain stem,

bronchoconstriction and increased bronchial secretion, and flaccid

paralysis of respiratory muscles

Methylparathion, azynphosmehtyl, chlorpyrifos, diazinon, malathion,

diclorvos, methamidophos, sarvin

The first signs appears to be muscarinic, which may or may not be in combination with nicotinic signs. While respiratory failure is a hallmark of severe OP poisoning, mild poisoning

and/or early stages of an otherwise severe poisoning may

display no clear-cut signs and symptoms.

The interaction of OPs with AChE has been studied in much

detail. OPs with a P=O moiety phosphorylate an hydroxyl group on

serine in the active (esteratic) site of the enzyme, thus impeding its

action on the physiological substrate (Fig. 22-3). The first reaction

leads to the formation of a Michaelis complex, while a subsequent

reaction leads to phosphorylatedAChE (Table 22-10). Rates of these

two reactions, that are usually very rapid, indicate the affinity of the

enzyme for a given OP. The bond between the phosphorus atom and

the esteratic site of the enzyme is much more stable than the bond

between the carbonyl carbon of acetate (in acetylcholine) at the same

enzyme site. While breaking of the carbon–enzyme bond is complete

in a few microseconds, breaking of the phosphorus-enzyme

bond can take from a few hours to several days, depending on the

chemical structure of the OP.

Phosphorylated AChE is hydrolyzed

by water at a very slow rate (Fig. 22-3; Table 22-10), and the rate

of “spontaneous reactivation” depends on the chemical nature of

the R substituents. Reactivation decreases in the order demethoxy

> diethoxy _ diisopropoxy (Gallo and Lawryk, 1991). Whereas

water is a weak nucleophilic agent, certain hydroxylamine derivatives,

known as oximes, can facilitate dephosphorylation of AChE,

and are utilized in the therapy of OP poisoning

Poisoning treatment: In case of dermal

exposure, contaminated clothing should be removed, and the skin

washed with alkaline soap. In case of ingestion, procedures to reduce absorption from the

gastrointestinal tract do not appear to be very effective (Lotti, 2001).

Atropine represents the cornerstone of the treatment for OP poisoning;

it is a muscarinic receptor antagonist, and thus prevents the

action of accumulating acetylcholine on these receptors. Atropine

is preferably given intravenously, though the intramuscular route

is also effective. The best clinical approach is to administer doses

of atropine large enough to achieve evidence of atropinization, i.e.,

flushing, dry mouth, changes in pupil size, bronchodilation, and increased

heart rate; atropinization should be maintained for at least 48

hours (Lotti, 2001). Indicative doses of atropine are 1 mg or 2–5 mg

in case of mild or moderate poisoning, respectively. Higher doses

by continuous infusion may be required in severe cases. Overdosage

with atropine is rarely serious in OP poisoned patients. Oximes, such as pralidoxime (2-PAM) are also used in the therapy

of OP poisoning. 2-PAM contains a positively charged atom

capable of attaching to the anionic site of AChE, and facilitate. dephosphorylation of the enzyme (Fig. 22-4), thus restoring the

catalytic site of AChE to its function. However, this chemical reaction

occurs only when the phosphorylated AChE has not undergone

aging. Dosing regimens for various oximes depend on the

specific compound and the severity of OP poisoning. For example,

for pralidoxime chloride, an initial 1 g dose given intravenously is

recommended, followed after 15–30 minutes by another 1 g if no

improvement is seen. If still no improvement is seen, an infusion of

0.5 g/h can be started (Lotti, 2001).

OPs bearing two methoxy groups (malathion, methylparathion,

dimethoate) is considered to be rather resistant to oxime therapy.

Biochemical Measurements In addition to synapses, AChE is

also present in red blood cells (RBC). Additionally, BuChE, also

known as pseudo-cholinesterase, is found in plasma. The physiological

functions of these enzymes are yet to be discovered. Nevertheless because activity of both enzymes is usually inhibited upon

exposure to OPs, their measurement is widely used as an indication

of exposure, and/or biological effect of OPs. Neither measurement is specific for a

certain OP, and indeed, other insecticides, such as carbamates, also

inhibit AChE and BuChE. Several analytical methods are available to measure OPs and

their metabolites in body fluids; the parent compound is measured

in blood, whereas metabolites are measured in urine.

The Intermediate Syndrome A second distinct manifestation of

exposure to OPs is the so-called intermediate syndrome, which was

first conceptualized by clinicians in Sri Lanka involved in the treatment

of suicide attempts (Senanayake and Karalliedde, 1987). The

intermediate syndrome is seen in 20–50% of acute OP poisoning

cases, and has been observed following exposure to a large variety

of OPs. The syndrome develops one to several days after the

poisoning, during recovery from cholinergic manifestations, or in

some cases, when patients are completely recovered from the initial

cholinergic crisis. Prominent features of the intermediate síndrome. are a marked weakness of respiratory, neck, and proximal limb muscles.

Mortality due to respiratory paralysis and complications ranges

from 15–40%, and recovery in surviving patients usually takes up to

15 days. The intermediate syndrome is not a direct effect of AChE

inhibition, and its precise underlying mechanisms are unknown. One

hypothesis is that muscle weakness may result from nicotinic receptor

desensitization due to prolonged cholinergic stimulation (Lotti,

2001).

Organophosphate-Induced Delayed Polyneuropathy A few

OPs may also cause another type of toxicity, known as

organophosphate-induced delayed polyneuropathy (OPIDP). Signs

and symptoms include tingling of the hands and feet, followed by

sensory loss, progressive muscle weakness and flaccidity of the distal

skeletal muscles of the lower and upper extremities, and ataxia.

These may occur 2–3 weeks after a single exposure, when signs of

both the acute cholinergic and the intermediate syndromes have subsided.

OPIDP can be classified as a distal sensorimotor axonopathy.

Neuropathological studies in experimental OPIDP have evidenced

that the primary lesion is a bilateral degenerative change in distal

levels of axons and their terminals, primarily affecting larger/longer

myelinated central and peripheral nerve fibers, leading to breakdown

of neuritic segments and the myelin sheats (Ehrich and Jortner,

2001). OPIDP is not related to AChE inhibition.

However, only OPs whose chemical structure

leads to aging of phosphorylated NTE (by a process analogous

to that described for AChE) can cause OPIDP.

most recent expert reviews tend to conclude that

the balance of evidence does not support the existence of clinically

significant neuropsychological effects, neuropsychiatric abnormalities,

or peripheral nerve dysfunction in humans chronically exposed

to low levels of OPs. OPs as a class are not considered to be mutagenic, and there

is little evidence that they may be carcinogenic. Immunotoxicity of

OPs has been suggested from in vitro or high dose animal studies,

but evidence in humans is lacking

Carbamate insecticides have a variety of chemical structures

(Fig. 22-7), but all derive from carbamic acid, the majority being

N-methylcarbamates. They present different degrees of acute oral

toxicity, ranging from moderate to low toxicity such as carbaryl, extremely high toxicity, such as aldicarb (Fig. 22-7). Dermal toxicity

is lower, but skin penetration is increased by organic solvents

and emulsifiers present in most formulations. For the most

part, the metabolites are devoid of biological activity, but this is

not always the case. For example, two metabolites of aldicarb, the

sulfoxide and the sulfone, are more potent anticholinesterases than

the parent compound (Risher et al., 1987). The mechanism of toxicity

of carbamates is analogous to that of OPs, in that they inhibit

AChE. However, inhibition is transient and rapidly reversible, because

there is rapid reactivation of the carbamylated enzyme in the

presence of water (Table 22-10). Additionally, carbamylated AChE

does not undergo the aging reaction. However, differently

from OPs, acute intoxication by carbamates is generally resolved

within a few hours. AChE inhibitors and do not require

metabolic bioactivation, and enzyme activity returns to control levels

within two hours. The treatment of carbamate intoxication relies

on the use of the muscarinic antagonist atropine. Use of oximes

is generally not recommended, as 2-PAM has been shown to aggravate

the toxicity of carbaryl. Yet, oximes may

have beneficial effects in case of other carbamates such as aldicarb

(Ecobichon, 2001b). There are several cases of human poisoning associated

with exposure to various carbamates, in particular carbaryl. Carbamates can

inhibit NTE, but because carbamylated NTE cannot age, they are

thought to be unable to initiate OPIDP. Embryotoxicity or fetotoxicity are observed only at maternally

toxic doses

Mesenteric ischemia - Schwartz

Mesenteric Ischemia

Mesenteric ischemia can present as one of two distinct clinical syndromes: acute mesenteric ischemia and chronic mesenteric ischemia.

Four distinct pathophysiologic mechanisms can lead to acute mesenteric ischemia:

1. Arterial embolus 2. Arterial thrombosis 3. Vasospasm (also known as nonocclusive mesenteric ischemia) 4. Venous thrombosis

Embolus is the most common cause of acute mesenteric ischemia, and is responsible for more than 50% of cases. The embolic source is usually in the heart; most often the left atrial or ventricular thrombi or valvular lesions. Indeed, up to 95% of patients with acute mesenteric ischemia due to emboli will have a documented history of cardiac disease. Embolism to the superior mesenteric artery accounts for 50% of cases; most of these emboli become wedged and cause occlusion at branch points in the mid- to distal superior mesenteric artery, usually distal to the origin of the middle colic artery. In contrast, acute occlusions due to thrombosis tend to occur in the proximal mesenteric arteries, near their origins. Acute thrombosis is usually superimposed on pre-existing atherosclerotic lesions at these sites. Nonocclusive mesenteric ischemia is the result of vasospasm and usually is diagnosed in critically ill patients receiving vasopressor agents.

Mesenteric venous thrombosis accounts for 5 to 15% of cases of acute mesenteric ischemia and involves the superior mesenteric vein in 95% of cases.⁶⁰ The inferior mesenteric vein is only rarely involved. Mesenteric venous thrombosis is classified as primary if no etiologic factor is identifiable, or as secondary if an etiologic factor, such as heritable or acquired coagulation disorders, is identified.

Regardless of the pathophysiologic mechanism, acute mesenteric ischemia can lead to intestinal mucosal sloughing within 3 hours of onset and full-thickness intestinal infarction by 6 hours.

In contrast, chronic mesenteric ischemia develops insidiously, allowing for development of collateral circulation, and, therefore, rarely leads to intestinal infarction. Chronic mesenteric arterial ischemia results from atherosclerotic lesions in the main splanchnic arteries (celiac, superior mesenteric, and inferior mesenteric arteries). In most patients with symptoms attributable to chronic mesenteric ischemia, at least two of these arteries are either occluded or severely stenosed. A chronic form of mesenteric venous thrombosis can involve the portal or splenic veins and may lead to portal hypertension, with resulting esophagogastric varices, splenomegaly, and hypersplenism.

Severe abdominal pain, out of proportion to the degree of tenderness on examination, is the hallmark of acute mesenteric ischemia, regardless of the pathophysiologic mechanism. The pain typically is perceived to be colicky and most severe in the midabdomen. Associated symptoms can include nausea, vomiting, and diarrhea. Physical findings are characteristically absent early in the course of ischemia. With the onset of bowel infarction, abdominal distention, peritonitis, and passage of bloody stools occur.

Chronic mesenteric ischemia presents insidiously. Postprandial abdominal pain is the most prevalent symptom, producing a characteristic aversion to food ("food-fear") and weight loss. These patients are often thought to have a malignancy and suffer a prolonged period of symptoms before the correct diagnosis is made.

Most patients with chronic mesenteric venous thrombosis are asymptomatic because of the presence of extensive collateral venous drainage routes; this condition is usually discovered as an incidental finding on imaging studies. However, some patients with chronic mesenteric venous thrombosis present with bleeding from esophagogastric varices.

Hypernatremia, Liquids and electrolites Manual (Constain, Alfred)

Hypernatremia means serum Na >145 mmol /ml. Severe hypernatremia >160 mmol/ml has a mortality rate of 75%.

Comprehense three categories:

1. Normovolemic hypernatremia

2. Hypervolemic Hypernatremia

3. Hypovolemic Hypernatremia

1. Normovolemic hypernatremia: It can occur in a wide spectrum of entities that cross since the insipid diabetes to overhydration.

2. Hypervolemic Hypernatremia: Occur principally in the hyperosmolar saline solutions context.

3. Hypovolemic Hypernatremia: Is the most comun, can occur in insipid diabetes, chronic renal failure, deshydration, shock.

Like general rule the sodium reposition can't be >10mmol/L in 24 hours and can't be superior to 0.5mEq/h.

So there are two formules to correct the sodium in hypernatremia:

1. Na plasma variation= ([Na] in the solution available - [serum Na]) / (Percentage of body water +1)

2. Na plasma variation= ([Na + K] in the solution available - [serum Na] / (Percentage of body water)

[Na] in the solution available= For example, the normal saline solution has 154mEq/L. 0.2% saline solution has 34 mEq/L. Normally, the reposition of water in hypernatremia is performed with 0.2% and 0.45% saline solution.

Percentage of body water= Men: 0.6*weight in Kg , Women: 0.5*weight in Kg

Example

A 65 yo man arrives to emergency department with HR:122bpm, AP: 120/75 mmhg, RR: 18 bpm, weight: 72Kg. [Na]= 162. Oral mucose was dry. The final diagnose is Pulmonary tromboembolism. ¿How do you correct this severe hypernatremia?

Percentage of body water= 43.2L

If we use a 5% dextrose solution, the [Na]= 0 mEq/L

Na plasma variation= ( [0] - 162) / (43.2 + 1) = 3.67 mEq

The value that we are going to replace is 3.67mEq/L, but we got to replace it till 10mEq/24h, hence 10/3.67= 2.62 L 5% of dextrose, wich is 113,5ml /h. After the first date of replacement we can perform it at 1mEq/h (i.e second day)

Hypercalcemia - NEJM, liquids and electrolytes manual

Hypercalcemia

-Means a calcium level >10.4 mg/DL or a ionized calcium level >5.1 mg/DL. A mild to moderate hypercalcemia is from (10.4-13.5mg/DL) and a severe >13.5mg/DL.

-Every patient with hypercalcemia should has: albumin, PTH, [Urinary calcium], calcitriol, phosphorum and magnesium, Renal function

tests, ECG.

- The main treatment is liquid reposition with saline solution, and biphosphonates (specially in severe hypercalcemia) like Zolendronic and Alendronic Acid.

Ninety percent of cases of hypercalcemia overall are due to primary hyperparathyroidism or a malignant condition, but of those due to the latter, less than 1% are a consequence of Hodgkin's lymphoma.4 Similarly, among patients with Hodgkin's lymphoma, only 5% have hypercalcemia.5Hypercalcemia of malignancy typically occurs through the following mechanisms: a humoral effect mediated by PTHrP, osteolytic metastases, or ectopic 1-alpha-hydroxylation of 25-hydroxyvitamin D resulting in increased calcitriol levels.6 This last mechanism is characteristic of Hodgkin's lymphoma 7; the extrarenal production of calcitriol by the lymphoma or tumor-infiltrating macrophages substantially increases absorption of calcium from the intestine, raising the serum calcium level. In the normal state, 1-alpha-hydroxylase converts 25-hydroxyvitamin D to calcitriol under the control of PTH, in response to hypocalcemia. In contrast, the 1-alpha-hydroxylase in lymphoma cells or tumor-infiltrating macrophages is poorly sensitive to feedback from circulating PTH, leading to inappropriate calcitriol production.8

All patients with severe hypercalcemia require treatment to correct the serum calcium concentration, to restore euvolemia, and to address the underlying disease process. Volume resuscitation is central to recovery, followed by therapy to inhibit bone resorption, target the underlying cause of hypercalcemia, and induce calciuresis.9,10 In patients with calcitriol-mediated hypercalcemia, glucocorticoids are the therapy of choice, reducing calcitriol production by macrophages and typically correcting the serum calcium within 3 to 5 days after the initial dose.11For hypercalcemia of malignancy, bisphosphonates are the principal treatment — in particular, the potent agent zoledronic acid.

In this case, the elevated calcitriol level, with low levels of PTH and PTHrP, suggested lymphoma as the cause of the hypercalcemia and ultimately led to imaging, visualization of adenopathy not palpable on physical examination, definitive tissue diagnosis, and effective therapy. This case underscores the importance of measuring calcitriol levels while one searches for the underlying cause of hypercalcemia in cases unexplained by a high level of PTH or PTHrP

LIVER ABSCESS - SCHWARTZ'S 2010 REVIEW

Pyogenic liver abscesses also occur as a result of impaired biliary drainage, hematogenous infection arising from sources such as

IV drug abuse and teeth cleaning, and local spread of infection (diverticulitis or Crohn's disease). Pyogenic hepatic abscesses may be single or multiple and are more frequently found in the right lobe of the liver.41 The

abscess cavities are variable in size and, when multiple, may coalesce to give a honeycomb appearance. Approximately 40% of abscesses

are monomicrobial, an additional 40% are polymicrobial, and 20% are culture negative. The most common infecting agents are gramnegative

organisms. Escherichia coli is found in two thirds, and Streptococcus faecalis, Klebsiella, and Proteus vulgaris are also common.

Anaerobic organisms such as Bacteroides fragilis are also seen frequently. Staphylococcus and Streptococcus are more common in patients

with endocarditis and infected indwelling catheters

Patients usually are symptomatic with right upper quadrant pain and fever. Jaundice occurs in up to one third of affected patients. A

thorough history and physical examination are necessary to attempt to localize the primary causative site. Leucocytosis, an elevated

sedimentation rate, and an elevated alkaline phosphatase (AP) level are the most common laboratory findings. Significant abnormalities in

the results of the remaining liver function tests are unusual. Blood cultures reveal the causative organism in approximately 50% of cases.

Ultrasound examination of the liver reveals pyogenic abscesses as round or oval hypoechoic lesions with well-defined borders and a variable

number of internal echoes. CT scan is highly sensitive in the localization of pyogenic liver abscesses. The abscesses are hypodense and may

contain air-fluid levels indicating a gas-producing infectious organism as well as peripheral enhancement (Fig. 31-19). MRI of the abdomen

also can detect pyogenic abscesses with a high level of sensitivity but plays a limited role because of its inability to be used for imageguided

diagnosis and therapy.

The current cornerstones of treatment include correction of the underlying cause, needle aspiration, and IV antibiotic therapy. On

presentation, percutaneous aspiration and culture of the aspirate may be beneficial to guide subsequent antibiotic therapy. Initial antibiotic

therapy needs to cover gram-negative as well as anaerobic organisms. Aspiration and placement of a drainage catheter is beneficial for only

a minority of pyogenic abscesses, because most are quite viscous and drainage is ineffective. Antibiotic therapy must be continued for at

least 8 weeks. Aspiration and IV antibiotic therapy can be expected to be effective in 80 to 90% of patients. If this initial mode of therapy

fails, the patients should undergo surgical therapy, including laparoscopic or open drainage.

Amebic Abscess

Entamoeba histolytica is a parasite that is endemic worldwide, infecting approximately 10% of the world's population. Amebiasis is most

common in subtropical climates, especially in areas with poor sanitation. E. histolytica exists in a vegetative form and as cysts capable of

surviving outside the human body. The cystic form passes through the stomach and small bowel unharmed and then transforms into a

trophozoite in the colon. Here it invades the colonic mucosa forming typical flask-shaped ulcers, enters the portal venous system, and is

carried to the liver. Occasionally, the trophozoite will pass through the hepatic sinusoid and into the systemic circulation, which results in

lung and brain abscesses.

Amebae multiply and block small intrahepatic portal radicles with consequent focal infarction of hepatocytes. They contain a proteolytic

enzyme that also destroys liver parenchyma. The abscesses formed are variable in size and can be single or multiple. The amebic abscess is

most commonly located in the superior-anterior aspect of the right lobe of the liver near the diaphragm and has a necrotic central portion

that contains a thick, reddish brown, pus-like material. This material has been likened to anchovy paste or chocolate sauce. Amebic

abscesses are the most common type of liver abscesses worldwide.

Ultrasound and CT scanning of the abdomen are both very sensitive but nonspecific for the detection of amebic abscesses.41 CT scanning

also is useful in detecting extrahepatic involvement. Amebic abscesses usually appear as well-defined low-density round lesions that have

enhancement of the wall. They also usually appear somewhat ragged in appearance with a peripheral zone of edema. The central cavity

may have septations as well as fluid levels.

Metronidazole 750 mg tid for 7 to 10 days is the treatment of choice and is successful in 95% of cases. Defervescence usually occurs in 3 to

5 days. The time necessary for the abscess to resolve depends on the initial size at presentation and varies from 30 to 300 days.41 Both

ultrasound and CT of the liver can be used as follow-up after the initiation of medical therapy. Aspiration of the abscess is rarely needed

and should be reserved for patients with large abscesses, abscesses that do not respond to medical therapy, abscesses that appear to be

superinfected, and abscesses of the left lobe of the liver that may rupture into the pericardium.

Hydatid disease is due to the larval or cyst stage of infection by the tapeworm Echinococcus granulosus, which lives in the dog.42 Humans,

sheep, and cattle are intermediate hosts. The dog is infected by eating the viscera of sheep that contain hydatid cysts. Scolices, contained in

the cysts, adhere to the small intestine of the dog and become adult taenia, which attach to the intestinal wall. Each worm sheds

approximately 500 ova into the bowel. The infected ova-containing feces of the dog contaminate grass and farmland, and the ova are

ingested by sheep, pigs, and humans. The ova have chitinous envelopes that are dissolved by gastric juice. The liberated ovum burrows

through the intestinal mucosa and is carried by the portal vein to the liver, where it develops into an adult cyst. Most cysts are caught in

the hepatic sinusoids, and 70% of hydatid cysts form in the liver. A few ova pass through the liver and are held up in the pulmonary

capillary bed or enter the systemic circulation, forming cysts in the lung, spleen, brain, or bones.

The uncomplicated cyst may be silent and found only at autopsy or

incidentally. Occasionally, the affected patient presents with dull right upper quadrant pain or abdominal distention. Cysts may become

secondarily infected, involve other organs, or even rupture, which leads to an allergic or anaphylactic reaction.

The diagnosis of hydatid disease is based on the findings of an enzyme-linked immunosorbent assay (ELISA) for echinococcal antigens, and

results are positive in approximately 85% of infected patients.42 The ELISA results may be negative in an infected patient if the cyst has not

leaked or does not contain scolices, or if the parasite is no longer viable. Eosinophilia of >7% is found is approximately 30% of infected

patients. Ultrasonography and CT scanning of the abdomen are both quite sensitive for detecting hydatid cysts. The appearance of the cysts

on images depends on the stage of cyst development. Typically, hydatid cysts are well-defined hypodense lesions with a distinct wall. Ringlike

calcifications of the pericysts are present in 20 to 30% of cases. As healing occurs, the entire cyst calcifies densely, and a lesion with

this appearance is usually dead or inactive. Daughter cysts generally occur in a peripheral location and are typically slightly hypodense

compared with the mother cyst. MRI of the abdomen may be useful to evaluate the pericyst, cyst matrix, and daughter cyst characteristics.

Unless the cysts are small or the patient is not a suitable candidate for surgical resection, the treatment of hydatid disease is surgically

based because of the high risk of secondary infection and rupture. Medical treatment with albendazole relies on drug diffusion through the

cyst membrane. The concentration of drug achieved in the cyst is uncertain but is better than that of mebendazole, and albendazole can be

used as initial treatment for small, asymptomatic cysts. For most cysts surgical resection involving laparoscopic or open complete cyst

removal with instillation of a scolicidal agent is preferred and usually is curative. If complete cystectomy is not possible, then formal

anatomic liver resection can be used.

Ascariasis

Ascaris infection is particularly common in the Far East, India, and South Africa. Ova of the roundworm Ascaris lumbricoides arrive in the

liver by retrograde flow in the bile ducts. The adult worm is 10 to 20 cm long and may lodge in the common bile duct, producing partial bile

duct obstruction and secondary cholangitic abscesses. The ascaris may be a nucleus for the development of intrahepatic gallstones. The

clinical presentation in an affected patient may include any of the following: biliary colic, acute cholecystitis, acute pancreatitis, or hepatic

abscess.43 Plain abdominal radiographs, abdominal ultrasound, and endoscopic retrograde cholangiography (ERCP) all can demonstrate the

ascaris as linear filling defects in the bile ducts. Occasionally worms can be seen moving into and out of the biliary tree from the duodenum.

Treatment consists of administration of piperazine citrate, mebendazole, or albendazole in combination with ERCP extraction of the worms.

Failure of endoscopic extraction warrants surgical removal of the áscaris.

Schistosomiasis

Schistosomiasis affects >200 million people in 74 countries. Hepatic schistosomiasis is usually a complication of the intestinal disease,

because emboli of schistosomiasis ova reach the liver via the mesenteric venous system. Eggs excreted in the feces hatch in water to

release free-swimming embryos, which enter snails and develop into fork-tailed cercariae. They then re-enter human skin during contact

within infected water. They burrow down to the capillary bed, and at that point there is widespread hematogenous dissemination. Those

entering the intrahepatic portal system grow rapidly, and a granulomatous reaction occurs. The degree of resultant portal fibrosis is related

to the adult worm load.

Schistosomiasis has three stages of clinical symptomatology: the first includes itching after the entry of cercariae through the skin; the

second includes fever, urticaria, and eosinophilia; and the third involves hepatic fibrosis followed by presinusoidal portal hypertension.

During this third phase the liver shrinks, the spleen enlarges, and the patient may develop complications of portal hypertension while

hepatic function is maintained. Active infection is detected by stool examination. Serologic tests indicate past exposure without specifics

regarding timing. A negative serologic test result rules out schistosomal infection. Serum levels of transaminases are usually normal, but the

AP level may be mildly elevated. A decreased serum albumin level is usually the result of frequent GI bleeds and decreased nutrition.

Medical treatment of schistosomiasis includes education regarding hygiene and the avoidance of infected water. Treatment with praziquantel

40 to 75 mg/kg as a single dose is the treatment of choice for all forms of schistosomiasis and produces few side effects. GI bleeding

usually is controlled by endoscopic variceal ligation. However, in a patient with refractory GI portal hypertensive bleeding, distal splenorenal

shunt or gastric devascularization and splenectomy need to be considered.

SPLEEN TRAUMA

Management of spleen (closed) trauma

· Spleen trauma in the majority of cases can be managed

with non operative management.

· A patient with spleen trauma unstable goes for a FAST, if is

positive then goes for operating room

· A patient with spleen trauma stable goes for a CT, if there is

bleeding or if the score of spleen injury is III or more, then the

angioembolization or the surgery is indicated.

The decision to employ the NOM pathway for

blunt splenic injury requires the patient to meet several

criteria. The first and foremost is hemodynamic

stability with the absence of any suspected associated

intra-abdominal injury

Certainly there are several clear absolute

contraindications which include the patient who is

receiving or will receive systemic anticoagulation.

Special consideration is in order for injured pregnant

women with viable preterm fetuses who would not

tolerate the stress of NOM failure. Also the patient

with multiple injuries or traumatic brain injury with

a mid to high grade splenic injury poses a particular

challenge to NOM.

The question of where to admit should be based

on injury grade. It is our institutional practice to admit

all injuries grade III or above to the intensive care unit.

Grade I and II injuries can be admitted to a less intensive

monitored setting. Certain grade I injuries may not

require admission and observation, but always while

taking into account that CT is notorious for underestimating

injury. The period of observation is debatable

and the clinical condition and progress of the patient

should play a role in deciding duration. Multiple studies

have concluded that most failures of NOM occur in

the first 72 hours of admission. Smith and colleagues

suggest that if hematocrit and pulse are stable after 48

hours, then patients can be ambulated and fed.8 The

hematocrit should be checked frequently for high grade

injuries and less frequently for grade I and II injuries