Amanita phalloides

Etiology

A. phalloides is the most toxic of the world’s cyclopeptide-containing mushrooms.

• Also known as “death cap” mushroom
• Responsible for 90% of fatal mushroom poisonings worldwide
• Appearance:
  • Pale, yellowish, or olive-green
  • Symmetric cap and stem
  • Bulbous base
  • Free, white lamellae
  • Resemble several edible mushrooms

Pathophysiology

The toxicity of A. phalloides is caused by amatoxins and phallotoxins. 

Amatoxins:

• Cyclic octapeptide (primarily alpha-amanitin)
• Heat stable and water insoluble
• Inhibit RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase II → interfere with protein synthesis → apoptosis
• Responsible for hepatic, renal, and encephalopathic effects 

Phalloidin:

• Cyclic heptapeptide
• Interrupts the actin polymerization–depolymerization cycle and impairs cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane function
• Causes self-limited gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis-like effects 6–12 hours after ingestion

Clinical presentation

Toxicity occurs over several days and usually develops in 3 characteristic stages:

Stage I: 

• Occurs 6–12 hours after ingestion and appears to resolve within 24 hours
• Symptoms: 
  • Abdominal cramping
  • Vomiting
  • Profuse watery diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (may contain blood and mucus) 
• Potential consequences:
  • Dehydration
  • Hypovolemia
  • Acute renal failure
  • Shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock

Stage II:

• May appear to improve clinically
• Ongoing liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver damage is occurring, as seen by laboratory abnormalities.
• This stage may last 2–3 days.

Stage III:

• Liver failure:
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
  • Coagulopathy
  • Encephalopathy
• Multiorgan dysfunction:
  • Renal failure
  • Pancreatitis
• Death may occur 1–2 weeks after the ingestion.

Diagnosis

The diagnosis typically relies on the history and presentation.

Laboratory abnormalities:

• Stage I (dehydration):
  • Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia
  • Metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis
• Stages II and III (multiorgan dysfunction):
  • ↑ Serum aminotransferase levels 
  • ↑ PT and aPTT
  • ↑ Lipase and amylase
  • ↑ Creatinine

Amatoxin levels:

• Not routinely available, but may be available through reference laboratories
• Urine testing is preferred.

Management

No definitive antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Overview of Antidotes is available, so management is largely supportive.

• Consultation with poison control
• Gastric decontamination (activated charcoal)
• Aggressive IV fluid hydration for gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis
• Correct electrolyte abnormalities
• Therapy to decrease amatoxin uptake:
  • Silibinin dihemisuccinate
  • Penicillin G
• Antioxidant therapy for hepatotoxicity:
  • N-acetylcysteine
  • Cimetidine
  • Vitamin C
• Liver transplantation for liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure

Tropane Alkaloid Plants

Etiology

• The tropane alkaloids include:
  • Atropine
  • Scopolamine
  • Hyoscyamine
• Tropane alkaloid plants represent a very diverse group:
  • Datura species (jimson weed, angel’s trumpet, thorn apple)
  • Hyoscyamus niger (henbane)
  • Atropa belladonna (deadly nightshade)
  • Mandragora officinarum (mandrake)
• These plants have historically been used for their hallucinogenic and medicinal properties.

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Pathophysiology

Toxicity from tropane alkaloids causes anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs poisoning through antagonism of central and peripheral muscarinic receptors.

Clinical presentation

Symptoms usually occur 30–60 minutes after ingestion and may continue for 24–48 hours, manifesting as a classic anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs toxidrome.

• Tachycardia
• Hyperthermia
• Dilated pupils → blurred vision
• Urinary retention
• Hot, dry, flushed skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin
• Dry mucous membranes
• Neurologic signs and symptoms:
  • Disorientation
  • Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium
  • Hallucinations
  • Psychosis
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures

Mnemonic:

The presentation of an anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs toxidrome can be remembered with:

• “Red as beet” (flushed skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin)
• “Blind as a bat” (mydriasis)
• “Dry as a bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones” (dry mucous membranes)
• “Hot as a hare” (anhidrosis)
• “Mad as hatter” (altered mental status)
• “Full as a flask” (urinary retention)

Diagnosis

The diagnosis of tropane alkaloid toxicity is clinical.

Management

• Assess and address the patient’s airway, breathing, and circulation (ABC assessment).
• Consider gastric decontamination.
• Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines for seizure and agitation
• Physostigmine is the antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Overview of Antidotes.

Toxicodendron Plants

Etiology

• Members of the plant genus, Toxicodendron
• In North America, this includes:
  • Poison ivy (T. rydbergii, T. radicans)
  • Poison oak (T. diversilobum, T. toxicarium)
  • Poison sumac (T. vernix)

Pathophysiology

• Toxicodendron species contain the oleoresin urushiol.
• Contact with the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin → type IV hypersensitivity reaction Type IV hypersensitivity reaction Type IV hypersensitivity reaction, or delayed-type hypersensitivity, is a cell-mediated response to antigen exposure. The reaction involves T cells, not antibodies, and develops over several days. Presensitized T cells initiate the immune defense, leading to tissue damage. Type IV Hypersensitivity Reaction

Clinical presentation

An acute allergic dermatitis generally occurs within 4–96 hours, and complete resolution is expected within 7–21 days. Characteristics of the rash include:

• Intense pruritus
• Erythematous papules, plaques, vesicles, or bullae
• Linear arrangement

Diagnosis

The diagnosis of Toxicodendron dermatitis is based on exposure history and physical exam.

Management

• Clean all clothing and objects that may be contaminated with urushiol.
• Soothing measures
  • Oatmeal baths
  • Cold compresses
  • Calamine (a combination of zinc oxide and ferric oxide)
  • Burow’s solution (an aqueous solution of aluminum triacetate)
• Oral antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines
• Topical corticosteroids
• Systemic steroids for severe dermatitis

Cyanide Plants

Etiology

Many plants contain cyanogenic glycosides, such as amygdalin.

• Pits or seeds from: 
  • Cherry
  • Apricot
  • Peach
  • Plum
  • Pear
  • Apple
• Lima beans
• Clover
• Sorghum
• Almonds

Pathophysiology

• Chewing seeds and pits is required for toxicity.
• Amygdalin is ingested → converted to hydrogen cyanide by gut bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview → enters bloodstream
• Inactivates cytochrome oxidase → inhibits aerobic metabolism and ATP production
• Tissues cannot use available oxygen → functional hypoxia 
• Anaerobic metabolism takes over → lactic acid production

Clinical presentation

Signs and symptoms of cyanide poisoning Cyanide Poisoning Hydrogen cyanide is an extremely poisonous, colorless, flammable liquid used in multiple industries and includes rubber, plastic, and household paints. Exposure to cyanide can occur via inhalation, dermal contact, or intestinal ingestion. Cyanide Poisoning are delayed until several hours after ingestion, but may include:

• Cardiovascular:
  • Initial tachycardia → bradycardia → circulatory collapse
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Dysrhythmias
• Respiratory:
  • Hyperventilation (attempted compensation for metabolic acidosis)
  • Respiratory depression and failure 
• Neurologic:
  • Headache
  • Dizziness
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
  • Anoxic brain injury
• GI:
  • Nausea and vomiting 
  • Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
• Other:
  • Renal failure
  • Hepatic necrosis
  • Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis
  • Pink or cherry-red skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin (uncommon)

Diagnosis

The diagnosis is generally based on the clinical history and examination. The following may support the diagnosis.

• Anion gap metabolic acidosis
• ↑ Lactic acid
• Cyanide level: 
  • Usually not available in time to be of benefit
  • Confirms cyanide toxicity

Management

• ABC assessment
• Supportive management:
  • IV fluid hydration
  • Vasopressors for hypotension
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines for seizures
• Gastric decontamination
• Antidotes:
  • Hydroxocobalamin (1st-line treatment) 
    • Precursor of vitamin B₁₂
    • Binds cyanide
  • Amyl nitrite or sodium nitrite
    • Induce methemoglobinemia Methemoglobinemia Methemoglobinemia is a condition characterized by elevated levels of methemoglobin in the blood. Methemoglobin is the oxidized form of hemoglobin, where the heme iron has been converted from the usual ferrous (Fe2+) to the ferric (Fe3+) form. The Fe3+ form of iron cannot bind O2, and, thus, leads to tissue hypoxia. Methemoglobinemia
    • Provide alternative binding site for cyanide 
  • Sodium thiosulfate
    • ↑ Availability of sulfur donors for rhodanese
    • Transforms cyanide to thiocyanate → excreted by kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys

Cardiac Glycoside Plants

Etiology

Cardiac glycosides are found in a number of plants, including:

• Foxglove (Digitalis purpurea and D. lanata)
• Oleander (Nerium oleander and Thevetia peruviana)
• Lily of the valley (Convallaria majalis)
• Squill (Urginea maritima and U. indica)
• Ouabain (Strophanthus gratus)
• Dogbane (Apocynum cannabinum)
• Wallflower (Cheiranthus cheiri)

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Pathophysiology

Consuming plant parts or teas brewed from these plants can lead to toxicity.

• Cardiac glycosides bind to a cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane → reversible inhibition of the Na–K–adenosine triphosphatase pump
• This process leads to:
  • ↑ Intracellular Na → ↑ intracellular calcium → dysrhythmia
  • ↓ Intracellular K

Clinical presentation

Signs and symptoms of cardiac glycoside toxicity include:

Cardiac:

• Palpitations
• Bradycardia
• Arrhythmia:
  • Premature ventricular contractions
  • Atrioventricular block Atrioventricular block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular Block
  • Junctional rhythms
  • Ventricular tachycardia Ventricular tachycardia Ventricular tachycardia is any heart rhythm faster than 100 beats/min, with 3 or more irregular beats in a row, arising distal to the bundle of His. Ventricular tachycardia is the most common form of wide-complex tachycardia, and it is associated with a high mortality rate. Ventricular Tachycardia or fibrillation
• Chest pressure
• Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
• Light-headedness

GI symptoms: 

• Nausea and vomiting
• Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain

Neurologic symptoms: 

• Weakness
• Altered mental status

Diagnosis

The diagnosis will be suspected because of the history and clinical presentation and supported by the workup.

• Digoxin level:
  • Some plant glycosides can cross-react with digoxin assays.
  • A negative level does not rule out cardiac glycoside exposure.
• Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia
• ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Normal Electrocardiogram (ECG) to assess for arrhythmia

Management

• ABC assessment
• Supportive management:
  • Cardiac monitoring
  • Atropine for symptomatic bradycardia
  • Appropriate management of life-threatening arrhythmias
  • Electrolyte monitoring and correction of life-threatening hyperkalemia
• Gastric decontamination
• Antidote: digoxin-specific antibody fragments (Fab)

Comparative Chart of Toxic Plants

Table: Clinical features and management of toxic plant exposure

Plant	Clinical features	Emergency management
Amanita phalloides (death cap mushroom)	Alpha-amanitin toxicity: Gastroenteritis Severe hepatotoxicity Multiorgan dysfunction	No definitive antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Overview of Antidotes is available. Gastric decontamination Supportive care Liver transplantation for liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure
Atropa belladonna, jimson weed	Anticholinergic toxicity: Tachycardia Anhidrosis Mydriasis Urinary retention Altered mental status	Physostigmine Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines for agitation and seizure
Poison ivy, poison oak, poison sumac	Type IV hypersensitivity reaction: erythematous papules, vesicles, or bullae in a linear configuration	Symptomatic therapy Topical corticosteroids
Pits or seeds from cherry, apricot, peach, plum, pear, apple	Cyanide toxicity: Hemodynamic instability Dysrhythmia Hyperventilation CNS depression Seizure	Hydroxocobalamin Sodium nitrite Sodium thiosulfate
Lily of the valley, foxglove	Cardiac glycoside toxicity: Arrhythmia GI upset Weakness Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia	Digoxin-specific antibody fragments

Differential Diagnosis

• Gastroenteritis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach and intestines, commonly caused by infections from bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview, viruses, or parasites. Common clinical features of gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis include abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, vomiting, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and dehydration. Diagnostic testing with stool analysis or culture is not always required, but it can help determine the etiology in certain circumstances. Most cases are self-limited; therefore, the only required treatment is supportive therapy (fluids). 
• Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen toxicity: A toxic ingestion of acetaminophen may lead to severe hepatotoxicity. Patients may initially present with symptoms similar to those of gastroenteritis Gastroenteritis Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Gastroenteritis. Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen toxicity may progress to liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure, renal failure, and pancreatitis. An acetaminophen level can help confirm the diagnosis. Gastric decontamination should be attempted, along with N-acetylcysteine therapy. Liver transplantation may be required for fulminant liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver failure.
• Viral hepatitis: liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation caused by infection with hepatitis virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview: Patients may present with a viral prodrome of fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, anorexia, and nausea. RUQ abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, and transaminitis also occur. The diagnosis is made with viral serologic testing. Management of acute hepatitis is supportive.
• Amphetamine toxicity: intoxication with amphetamines causing a sympathomimetic Sympathomimetic Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (α, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs response. Patients may have tachycardia, hyperthermia, mydriasis, delirium, seizures, rhabdomyolysis, and renal failure. Unlike with anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs toxicity, patients are diaphoretic. The diagnosis is often made clinically and confirmed with a drug screen. Management includes supportive care and benzodiazepines.
• Hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism: Elevated levels of free thyroid hormones Thyroid hormones The 2 primary thyroid hormones are triiodothyronine (T3) and thyroxine (T4). These hormones are synthesized and secreted by the thyroid, and they are responsible for stimulating metabolism in most cells of the body. Their secretion is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Thyroid Hormones can result in hypermetabolism. Patients can have tachycardia, palpitations, anxiety, tremor, diaphoresis, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea. The diagnosis is confirmed with thyroid studies. Management depends on the etiology, but it may include methimazole, beta-blockers, radioactive iodine, and surgery.
• Contact dermatitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin in response to irritants. Pruritus, pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, microvesiculation (formation of small vesicles), and a burning sensation may occur. The diagnosis is clinical. Management involves removing the offending agent and reducing skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation with steroids or topical calcineurin inhibitors.
• Bullous pemphigoid Bullous pemphigoid Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In bullous pemphigoid, autoantibodies attack the hemidesmosomes, which connect epidermal keratinocytes to the basement membrane. This attack results in large, tense subepidermal blisters. Bullous Pemphigoid and Pemphigus Vulgaris: autoimmune blistering disease caused by antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins against hemidesmosomes. Patients are usually elderly and present with pruritic, tense, bullous lesions and spared mucosal surfaces. Triggers include medications, trauma, skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin conditions, and systemic disease. Biopsy with immunofluorescent staining is used for diagnosis. Management includes steroids, immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants, and antiinflammatory medications.
• Carbon monoxide poisoning Carbon monoxide poisoning Carbon monoxide (CO) is an odorless, colorless, tasteless, nonirritating gas formed by hydrocarbon combustion (e.g., fires, car exhaust, gas heaters). Carbon monoxide has a higher affinity to hemoglobin than oxygen, forming carboxyhemoglobin (COHb). Increased levels of COHb lead to tissue hypoxia and brain damage. Carbon Monoxide Poisoning: Inhalation of carbon monoxide causes displacement of oxygen from the hemoglobin, interfering with aerobic metabolism. Patients may suffer from headache, nausea, dyspnea, loss of consciousness, and seizures. Skin color may be cherry-red, though this is usually seen postmortem. An elevated carboxyhemoglobin level can provide the diagnosis. Management requires 100% oxygen or hyperbaric oxygen.