Nausea and Vomiting

Cyclic Vomiting Syndrome (CVS)
  • Diagnosis: 
    • Three or more recurrent discrete episodes of vomiting
    • Varying intervals of completely normal health between episodes
    • Episodes are stereotypical with regard to timing of onset, symptoms, and duration
  • Etiology
    • CVS and Migraines
    • Metabolic Disorders
      • Mitochondrial disorders of fatty acid oxidation (e.g., medium-chain acyl coenzyme A dehydrogenase deficiency), 
      • respiratory chain defects (e.g., MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Syndrome), and 
      • mitochondrial DNA deletions 
    • Dysautonomia
    • Hypothalamic-pituitary-adrenal axis 
    • Food allergy
    • Cataminal CVS
    • Chronic Cannabis use
  • Ref: 
    • Uptodate
  • DDx

Nausea, Vomitting, and Hiccups
  • Area Postrema Syndrome 

    • Anatomy
      • The area postrema (AP) is a Circumventricular Organ (CVO) which is devoid of a blood–brain barrier located in the medulla. It both receives neural afferent inputs and responds to circulating hormones. The AP projects to nuclei in the CNS known to be important in autonomic regulation of cardiovascular function, including the NTS, dorsal motor nucleus of the vagus, ventrolateral medulla and lateral parabrachial nucleus. Thus, it is well situated anatomically to influence cardiovascular regulation. 
    • Physiology
      • The AP is believed to be involved in the central actions of peptide hormones, such as AVP and Ang II, to modulate control of the sympathetic nervous system (SNS) and arterial pressure. 
      • Precise regulation of cardiovascular function requires the central integration of neural and humoral signals from the periphery. These signals provide the central nervous system (CNS) with information related to blood pressure and blood volume, so that appropriate adjustments in the output of efferent systems controlling these vari- ables can be made. Neural inputs related to cardiovascular control arise primarily from cardiopulmonary receptors in the great vessels
      • Peptide hormones, such as arginine vasopressin (AVP) and angiotensin (Ang)II are believed to exert their central effects primarily through actions at circumventricular organs (CVO), which are devoid of a blood–brain barrier.  Thus, by acting at CVO, these hormones have the potential to exert profound effects on the cardiovascular system. The effects of these humoral influences may be direct or may occur through modulation of the central response to neural inputs. To main- tain adequate cardiovascular control under different conditions, neural reflex mechanisms must be plastic, adapting to different physiological and pathophysiological states. At least some of this ability to modulate cardiovascular reflexes is due to hormonal influences mediated through CVO.
    • References
  • Pathogenesis of N and V 
    • Vomitting is coordinated by Brainstem and is effected by gut, pharynx, and somatic musculature 
    • Mechanisms underlying nausea are poorly understood but likely involve the cerebral cortex, as nausea requires conscious perception. (Ref: Harrison's)
    • Brainstem nuclei—including the nucleus tractus solitarius; dorsal vagal and phrenic nuclei; medullary nuclei regulating respiration; and nuclei that control pharyngeal, facial, and tongue movements—coordinate initiation of emesis. Neurokinin NK1, serotonin 5-HT3, and vasopressin pathways participate in this coordination.  (Ref: Harrison's)
    • Somatic and visceral muscles respond stereotypically during emesis. Inspiratory thoracic and abdominal wall muscles contract, producing high intrathoracic and intraabdominal pressures that evacuate the stomach. The gastric cardia herniates above the diaphragm, and the larynx moves upward to propel the vomitus. Distally migrating gut contractions are normally regulated by an electrical phenomenon, the slow wave, which cycles at 3 cycles/min in the stomach and 11 cycles/min in the duodenum. During emesis, the slow wave is abolished and is replaced by orally propagating spikes that evoke retrograde contractions that assist in expulsion of gut contents. (Ref: Harrison's)
    • The area postrema, in the medulla, responds to bloodborne stimuli (emetogenic drugs, bacterial toxins, uremia, hypoxia, ketoacidosis) and is termed the chemoreceptor trigger zone(Ref: Harrison's)
    • The area postrema is served by nerves acting on 5-HT3, M1, H1, and dopamine D2 subtypes
    • Cannabinoid CB1 pathways may participate in the cerebral cortex
      • (Ref: Harrison's)