Impaired microvascular function is seen in a vast majority, if not all, of patients with TTS and is currently one of the most supported theories. Most of the dysfunction occurs as a result of abnormalities within the endothelial linings of blood vessels supplying the heart. In TTS, these highly sensitive interior linings of the vessels have reduced functionality which create dysregulation of vascular tone and predispose the individual to vasoconstriction. When the increased vasoconstrictor effects of catecholamines are introduced, the result is acute cardiac ischemia. Catecholamine-induced myocyte injury: It has been suggested that the response to catecholamines (such as epinephrine and norepinephrine, released in response to stress) leads to heart muscle dysfunction that contributes to takotsubo cardiomyopathy. The effects of this toxicity can be greater in those with a predisposition to anxiety or panic disorders. Delivery of catecholamines (epinephrine, norepinephrine) via circulating blood and through direct delivery from cardiac nerves is increased by the stimulation of stress control centers of the brain. During an emotionally or physically stressful event, brain centers initiate the sympathetic nervous pathways and increase myocardial activity. Excessive catecholamine stimulation has a toxic effect on cardiac muscle cells which creates necrosis of the contractile units of cells similarly seen during acute myocardial infarction. The increased workload of cardiac muscle created by the stimulation of catecholamines, increases the need for more blood and oxygen to these muscles to sustain function. When these demands are unable to be met, the heart is starved of blood and oxygen and begins to die.
Symptoms in humans include all those of typical metabolic acidosis (nausea, vomiting, generalized muscle weakness, and laboured and deep breathing). Causes
The several different causes of lactic acidosis include:
Genetic conditions
Biotinidase deficiency, multiple carboxylase deficiency, or nongenetic deficiencies of biotin
Diabetes mellitus and deafness
Fructose 1,6-bisphosphatase deficiency
Glucose-6-phosphatase deficiency
GRACILE syndrome
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
Pyruvate dehydrogenase deficiency
Pyruvate carboxylase deficiency
Leigh syndrome
Drugs
Linezolid
Paracetamol/acetaminophen poisoning
Metformin: this risk is low (less than 10 cases for 100,000 patient years), but the risk of metformin-induced lactic acidosis (MALA) increases in certain situations where both the plasma levels of metformin are increased and lactate clearance is impaired. The older related and now withdrawn drug phenformin carried a much higher risk of lactic acidosis. Isoniazid toxicity
Propofol
Epinephrine
Propylene glycol (D-lactic acidosis)
Nucleoside reverse-transcriptase inhibitors
Abacavir/dolutegravir/lamivudine
Emtricitabine/tenofovir
Potassium cyanide (cyanide poisoning)
Fialuridine
Other
Thiamine deficiency (especially during TPN)
Impaired delivery of oxygen to cells in the tissues (e.g., from impaired blood flow (hypoperfusion))
Bleeding
Polymyositis
Ethanol toxicity
Sepsis
Shock
Advanced liver disease
Diabetic ketoacidosis
Excessive exercise (overtraining)
Regional hypoperfusion (e.g., bowel ischemia or marked cellulitis)
Cancers such as Non-Hodgkins and Burkitt lymphomas
Pheochromocytoma
Tumor lysis syndrome
D-lactic acidosis due to intestinal bacterial flora production in short gut syndrome

Pathophysiology
Glucose metabolism begins with glycolysis, in which the molecule is broken down into pyruvate in ten enzymatic steps. A significant proportion of pyruvate is converted into lactate (usually 10:1). The human metabolism produces about 20 mmol/kg of lactic acid every 24 hours. This happens predominantly in tissues (especially muscle) that have high levels of the "A" isoform of the enzyme lactate dehydrogenase (LDHA), which predominantly converts pyruvate into lactate.