lactic acidosis ( la ) is known to occur in patients of leukemia and lymphoma as a terminal event .
it was first described in patients with acute leukemia by field et al . in 1963 .
diagnostic criteria of la are ph less than 7.35 along with plasma lactate concentration greater than 5 mmol / l .
however , la as the initial presentation of non - hodgkins lymphoma ( nhl ) is extremely rare .
a 35-year - old male presented with intermittent fever , loss of appetite and fatigue of 5 months duration .
he was afebrile with a pulse of 140/min , and a respiratory rate of 36/minute .
pallor , pedal edema along with right cervical lymphadenopathy was present . on systemic examination a firm mass of 10 cm
hemoglobin was 5.1 gm / dl , wbc 9200/cu mm , platelet count 2,72,000/cu mm ; renal and liver functions were normal with serum ( sr ) urea 37 mg / dl , sr creatnine 0.7 mg / dl , sr bilirubin 0.5 mg / dl , sr sgot 52 units / l , sr sgpt
his sr ldh was raised with a value of 876 iu / l and sr albumin was markedly low 1.8 gm / dl .
blood gas analysis showed ph 7.17 , pco2 23 mmhg , hco3 8.4mmol / l , serum lactate 12.7 mmol / l , suggestive of metabolic acidosis [ table 1 ] .
computerized tomography ( ct ) scan showed dilated small bowel loops with mural thickening along with the presence of homogenous mesenteric and retroperitoneal masses measuring about 7 cm along with mediastinal lymph nodes .
a biopsy of the abdominal lymph node revealed nhl ( subtype dlbcl ) , immunohistochemistry of tumor was positive for cd20 and negative for cd3 and cd10 . bone marrow was not involved by abnormal lymphoid cells .
as blood sugar , urea and creatinine were normal , blood cultures were sterile , no history of intake of metformin or other medication causing la and other common causes of metabolic acidosis were ruled out .
the patient was started on soda bicarbonate , broad spectrum antibiotics , although no focus of infection was detected .
simultaneously , he was given cyclophospamide 500 mg on day 1 and day 2 , dexamethasone 8 mg three times daily day 1 to day 4 and doxorubicin 30 mg on day 3 .
patient 's vitals improved gradually and after 1 week , his lactate level came down along with improvement in ph and bicarbonate levels .
he subsequently received six courses of r - chop ( rituximab , cyclophospamide , doxorubicin , vincristine , prednisolone)-based chemotherapy .
he had a partial response that was short lasting and developed progression of lymphoma within 2 months of sixth course of r - chop .
showing following parameters [ arterial blood gas , blood sugar , vitals ] before and after adding chemotherapy
lactic acid is a degradation product of glucose in anaerobic conditions . in anaerobic conditions ,
there are two types of la , hypoxic ( type a ) and non - hypoxic ( type b ) .
malignancy is often associated with type b. causes of la in malignancy are either due to overproduction of la or under utilization of la or both .
tumor cell have a different metabolic milieu as compared to non - malignant cells . rapidly dividing tumors
this leads to anaerobic glycolysis with activation of ldh and production of lactate . however , hypoxia is not the only mechanism of high lactate level in malignancy .
otto warburg in 1930 demonstrated that cancer cells rely on glycolysis even in the presence of oxygen , a phenomenon known as aerobic glycolysis  warburg effect  .
apart from hypoxic environment , elevated lactate level may also occur due to liver metastasis , over expression of type ii hexokinase , regulatory effect of insulin - like growth factor . in malignant cells even under aerobic conditions
there is increased activation of mitochondrial - bound type 2 hexokinase , a rate - limiting enzyme of glycolysis .
this occurs due to aberrant production of insulin - like growth factors along with its binding proteins and tumor necrosis factor ( tnf- ) by tumor tissue . in our patient ,
the poor prognostic impact of la in malignancy can be judged from fact that out of the total 29 published cases of lymphoma with la , 25 eventually died ( pubmed search database ) .
hence , la in lymphoma portends a very poor prognosis . the molecular basis for this may be due to a functional impairment of cytotoxic t cells .
activated t lymphocytes are also dependent on glycolysis during the period of proliferation and cytokine production and thus produce lactate .
this transport requires proton - linked monocarboxylate transporters , which co - transport protons and lactate anions following a concentration gradient .
but lactate produced by the tumors disrupts the lactate gradient between intracellular and extracellular compartment of cytotoxic t cells present within the tumor bed .
role of buffering agents like soda bicarbonate to treat la is only supportive and temporary .
anemia can rarely be a cause of la in this case as la persisted even after blood transfusion .
in this case though there were other confounding factors like low albumin , b - symptoms and bulky disease that are causes of poor prognosis so we can say that la has an additive effect for poor prognosis in high - risk cases of lymphoma .
the literature review of the cases of la in lymphoma also suggests that these cases were having one or other high - risk features along with la .
la is rare in patients with lymphoma . it is associated with high tumor burden along with aggressive biological and clinical behavior and
 lactic acidosis ( la ) has been reported to be associated with high grade lymphoma as a terminal event . 
 its causes are multi - factorial . 
 it can either occur due to overproduction of lactic acid by rapidly dividing tumor or due to its underutilization due to involvement of liver by lymphomatous deposits . 
 the prognosis of lymphoma associated with la is dismal . 
 we present a patient of non - hodgkins lymphoma ( nhl ) who presented with la , after an initial response succumbed . 
INTRODUCTION
CASE REPORT
DISCUSSION
CONCLUSION