A 28-year-old man with a long history of intravenous drug abuse and chronic hepatitis B presented with jaundice.Physical examination revealed an anemic, malnourished man with dependent pitting edema and ascites. He had the following profile
A) Blood biochemistry:
1) Total protein 8.2 g./dL
2) Albumin 2.6 g/dl
3) Globulins 5.6 g/dL
4) Calcium 6.8 mg/dL,
5) BUN 6 mg/dL
6) Creatinine 0.9 mg/dL
7) Total Bilirubin 6.0 mg/dL
8) AST (Aspartate amino transferase) 200 U/L
9) ALT (Alanine amino transferase)350 U/L
10) ALP(Alkaline Phosphatase) 180 U/L
11) LDH (Lactate Dehydrogenase)300 U/L
12) CBC: macrocytic anemia with hyper segmented neutrophils, mild neutropenia, and mild thrombocytopenia
13) Prothrombin time (PT) was prolonged and did not correct with intramuscular vitamin K administration.
B) Urinalysis: Positive for Bilirubin
i) What is the clinical significance of his abnormal liver function tests, hypoalbuminemia, and prolonged prothrombin time that does not correct with intramuscular vitamin K?
ii) What is the clinical significance of hypocalcemiain this patient?
iii) Why does he have a low serum BUN?
iv) What is the most likely cause of the macrocytic anemia?
Cause for Abnormal liver function tests
The patient is most probably suffering from chronic end-stage liver disease secondary, most likely, to chronic hepatitis B.
The transaminases are moderately elevated, and ALT is higher than AST. In acute hepatitis, the transaminases would be higher owing to the presence of more liver tissue; however, in chronic hepatitis, the lossof hepatocytes and replacement by fibrosis results in less of an increase.
2) Hypoalbuminemia and a prolonged prothrombin time(PT)are markers of increased severity of liver disease, since both depend on the ability of the liver to synthesize proteins (albumin and coagulation factors).Inability to correct the PT with vitamin K signifies that the liver is unable to synthesize the precursor vitamin K-dependent factors II, VII, IX, and X for(γ-carboxylation by vitamin K into functional coagulation factors). So the synthetic functions of liver are impaired.
3) Hypocalcemia- The total serum calcium represents the calcium that is bound to albumin (40%), other anions (13%), and free (ionized calcium; 47%). Low ionized calcium may result in tetany. Therefore, in the presence of hypoalbuminemia, the most common cause of hypocalcemia, the total calcium is decreased while the ionized calcium is normal, so tetany is not present. Hypocalcaemia is partly due to hypoalbuminemia and to hypovitaminosis D secondary to his liver disease. The liver is responsible for the first hydroxylation step in vitamin D metabolism after its reabsorption from the small bowel. Hypocalcemia is a stimulus for secondary hyperparathyroidism, which is likely, to be present in this patient as well.
4) Low BUN level-owing to location of the urea cycle in the liver, the presence of liver disease seriously hampers the normal function of disposing of ammonia in the urea cycle. Hence, in chronic liver disease, the serum BUN is low while the ammonia level is increased.
5) Macrocytic anemiaThe macrocytic anemia with hyper segmented neutrophils in this patient is more likely secondary to folate rather than to B12 deficiency owing to the 3- to4-month supply of folate in the liver versus the 6- to 9-year supply of B12.This is easily verified by measurement of serum folate, RBC folate, and B12.
6) Elevated LDH-The elevated serum LDH is most likely secondary to destruction of the macrocytic RBCs (which contain increased LDH1 isoenzyme) in the bone marrow by macrophages(ineffective erythropoiesis).
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