What is the mechanism of action in organophosphates poisoning?
Correct Answer A:
Organophosphate compounds are a diverse group of chemicals used in both domestic and industrial settings. Examples of organophosphates include: insecticides, nerve gases and herbicides. Nerve agents have also been used in battle, notably in Iraq in the 1980s. Additionally, chemical weapons still pose a very real concern in this age of terrorist activity.
The primary mechanism of action of Organophosphate pesticides is inhibition of acetylcholinesterase (AChE). AChE is an enzyme that degrades the neurotransmitter acetylcholine (ACh) into choline and acetic acid. ACh is found in the central and peripheral nervous system, neuromuscular junctions, and red blood cells (RBCs).
Organophosphates inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of AChE. This leads to an increase in the amount of Acetylcholine in the body and a wide variety of reactions.
A 42-year-old man presents with dark skin (skin hyperpigmentation) and a palpable liver. His father died of cirrhosis.
What is the most likely diagnosis?
Correct Answer B:
Hemochromatosis is an inherited disorder characterized by excessive iron accumulation causing tissue damage. Symptoms do not develop until organ damage, often irreversible, develops. Symptoms include fatigue, hepatomegaly, bronze skin pigmentation, loss of libido, arthralgias, and manifestations of cirrhosis, diabetes, or cardiomyopathy.
90% of patients will present with excessive skin pigmentation. Diagnostic testing will reveal that the serum iron is increased (> 300 mg/dL). Phlebotomy is the simplest method of excess iron removal in most cases.
The other choices would not typically present with dark skin pigmentation.
A 42-year-old man presents with fatigue and joint pain. On physical exam he is found to have dark skin and a palpable liver. His urine shows glucosuria.
Which of the following will help you in the diagnosis?
Primary hemochromatosis is an inherited disorder characterized by excessive iron accumulation causing tissue damage. Symptoms do not develop until organ damage, often irreversible, develops. Symptoms include fatigue, hepatomegaly, bronze skin pigmentation, loss of libido, arthralgias, and manifestations of cirrhosis, diabetes, or cardiomyopathy. Diagnosis is based on serum iron studies and gene assay. Treatment is with serial phlebotomies.
Because iron accumulates in multiple sites, symptoms can develop referable to many possible organs or systemically. In women, fatigue and nonspecific constitutional symptoms develop early; in men, cirrhosis or diabetes is often the initial presentation.
Serum iron is increased (> 300 mg/dL). Serum transferrin saturation is usually > 50% and often > 90%. Serum ferritin is increased.
A 50-year-old man with a history of hemochromatosis presents to the emergency room vomiting up bright red blood. He had his most recent phlebotomy yesterday. His blood pressure is 110/85 mmHg, his pulse 115 beats per minute; his face is flushed, and he is diaphoretic. During the physical examination, splenomegaly and a venous pattern on his chest and abdomen are noted. He seems somewhat drowsy and confused but has no focal neurologic signs.
What is the most likely cause of this patient's bleeding?
Long term complications of hemochromatosis include liver cirrhosis. Portal hypertension is caused most often by cirrhosis (in developed countries), schistosomiasis (in endemic areas), or hepatic vascular abnormalities. Consequences include esophageal varices and portal-systemic encephalopathy.
Portal hypertension is asymptomatic; symptoms and signs result from its complications. The most dangerous is acute esophageal variceal bleeding. Patients typically present with sudden painless upper GI bleeding, often massive. Bleeding from portal hypertensive gastropathy is often subacute or chronic. Ascites, splenomegaly, or portal-systemic encephalopathy may be present.
Portal hypertension is inferred in a patient with chronic liver disease by the presence of collateral circulation, splenomegaly, ascites, or portal-systemic encephalopathy. Proof requires direct portal pressure measurement by a transjugular catheter, which is invasive and usually not performed. Imaging may help when cirrhosis is suspected.
Ultrasound or CT often reveals dilated intra-abdominal collaterals, and Doppler ultrasound can determine portal vein patency and flow.
Diagnosis is based on clinical criteria, often in conjunction with imaging studies and endoscopy. Treatment involves prevention of GI bleeding with endoscopy, drugs, or both, and sometimes with portocaval shunting.
Which one of the following is the best initial screening test for hemochromatosis?
Correct Answer E:
The diagnosis of hereditary hemochromatosis is based on a combination of clinical, laboratory, and pathologic criteria, including elevated serum transferrin saturation and elevated serum ferritin concentration. Elevated serum transferrin saturation is the earliest phenotypic abnormality. While this is the best initial screening test, results may be normal early in the course of the disease. In addition, because serum iron concentrations vary throughout the day and measurements may be affected by the ingestion of food, a test showing elevated serum transferrin saturation should be repeated as a fasting early-morning determination. Furthermore, the serum ferritin concentration and serum transferrin saturation may be elevated in 30%-50% of patients with acute or chronic viral hepatitis or alcoholic liver disease.
Serum ferritin concentration is a sensitive measure of iron overload, but it is also an acute-phase reactant and is therefore elevated in a variety of infectious and inflammatory conditions in the absence of iron overload. Consequently, it should not be used as the initial screening test to detect hereditary hemochromatosis.
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