B. Glyceraldehyde 3-phosphate from glycolysis is converted to glycerol 3phosphate, the initial acceptor of FA in triacylglycerol (TAG) synthesis (see figure at right). FA are available because of increased synthesis (from acetyl CoA, which is increased as a result of both increased production from the acetate product of acetaldehyde oxidation and decreased use in the TCA cycle), increased availability from lipolysis in adipose tissue, and decreased degradation. The TAG produced in the liver accumulate (due, in part, to decreased production of very-low-density lipoproteins) and cause fatty liver (steatosis). Hepatic steatosis is an early (and reversible) stage in alcohol-related liver disease. Subsequent stages are alcohol-related hepatitis (sometimes reversible) and cirrhosis (irreversible).
TQ2.The rise in NADH favors the reduction of pyruvate to lactate by lactate dehydrogenase. Lactate decreases the renal excretion of uric acid, thereby causing hyperuricemia, a necessary step in an acute gouty attack. [Note: The shift from pyruvate to lactate decreases the availability of pyruvate, a substrate for gluconeogenesis. This contributes to the hypoglycemia seen in AK.] TQ3.Prothrombin time (PT) measures the time it takes for plasma to clot after the addition of tissue factor (FIII), thereby allowing evaluation of the extrinsic (and common) pathways of coagulation. In the extrinsic pathway, FIII activates FVII in a calcium (Ca2+)-and phospholipid (PL)-dependent process (see figure at bottom right). FVII, like most of the proteins of clotting, is made by the liver. Alcohol-induced liver damage can decrease its synthesis. Additionally, FVII has a short half-life, and, as a γ-carboxyglutamate (Gla)-containing protein, its synthesis requires vitamin K. Poor nutrition can result in decreased availability of vitamin K and, therefore, decreased ability to clot. [Note: Severe liver disease results in prolonged PT and activated partial thromboplastin time, or aPPt.]
TQ4.Administration of folate can mask a deficiency in vitamin B12 by reversing the hematologic manifestation (macrocytic anemia) of the deficiency. However, folate has no effect on the neurologic damage caused by B12 deficiency. Over time, then, the neurologic effects can become severe and irreversible. Thus, folate can mask a deficiency of B12 and prevent treatment until the neuropathy is apparent.
III. Focused Cases
Case 1: Microcytic Anemia
Patient Presentation: ME is a 24-year-old man who is being evaluated as a follow-up to a preplacement medical evaluation he had prior to starting his new job.
Focused History: ME has no significant medical issues. His family history is unremarkable, but he knows little of the health status of those family members who remain in Greece.
Pertinent Findings: The physical examination was normal. Routine analysis of his blood included the following results:
Based on the data, hemoglobin (Hb) electrophoresis was performed. The results are as follows:
H = High; L = Low. [Note: HbA includes HbA1c.]
Diagnosis: ME has β-thalassemia trait (β-thalassemia minor) that is causing a microcytic anemia (see image at right). Ethnicity (such as being of Mediterranean origin) influences the risk for thalassemia.
Treatment: None is required at this time. Patients are advised that iron supplements will not prevent their anemia.