Biochemistry Lecture Notes - Uremia: Background, Pathophysiology, Etiology

Background

Uremia is a clinical syndrome associated with fluid, electrolyte, and hormone imbalances and metabolic abnormalities, which develop in parallel with deterioration of renal function. The term uremia, which literally means urine in the blood, was first used by Piorry to describe the clinical condition associated with renal failure.

Uremia more commonly develops with chronic kidney disease (CKD), especially the later stages, of CKD, but it also may occur with acute kidney injury (AKI) if loss of renal function is rapid. As yet, no single uremic toxin has been identified that accounts for all of the clinical manifestations of uremia. A number of toxins, such as parathyroid hormone (PTH), beta2 microglobulin, polyamines, advanced glycosylation end products, and other middle molecules, are thought to contribute to the clinical syndrome.

Read more: Biochemistry Lecture Notes - Uremia: Background, Pathophysiology, Etiology

Source: Medscape

Biochemistry Lecture Notes - Azotemia: Background, Pathophysiology, Etiology

Background

Azotemia is an elevation of blood urea nitrogen (BUN) and serum creatinine levels. The reference range for BUN is 8-20 mg/dL, and the normal range for serum creatinine is 0.7-1.4 mg/dL.

Each human kidney contains approximately 1 million functional units known as nephrons, which are primarily involved in urine formation. Urine formation ensures that the body eliminates the final products of metabolic activities and excess water in an attempt to maintain a constant internal environment (homeostasis). Urine formation by each nephron involves 3 main processes, as follows: 

• Filtration at the glomerular level 
• Selective reabsorption from the filtrate passing along the renal tubules 
• Secretion by the cells of the tubules into this filtrate 

Perturbation of any of these processes impairs the kidney’s excretory function, resulting in azotemia.

Read more: Biochemistry Lecture Notes - Azotemia: Background, Pathophysiology, Etiology.

Source: Medscape

The mechanisms and functions of spontaneous neurotransmitter release

Fast synaptic communication in the brain requires synchronous vesicle fusion that is evoked by action potential-induced Ca2+ influx. However, synaptic terminals also release neurotransmitters by spontaneous vesicle fusion, which is independent of presynaptic action potentials. A functional role for spontaneous neurotransmitter release events in the regulation of synaptic plasticity and homeostasis, as well as the regulation of certain behaviours, has been reported. In addition, there is evidence that the presynaptic mechanisms underlying spontaneous release of neurotransmitters and their postsynaptic targets are segregated from those of evoked neurotransmission. These findings challenge current assumptions about neuronal signalling and neurotransmission, as they indicate that spontaneous neurotransmission has an autonomous role in interneuronal communication that is distinct from that of evoked release.

Key points

• Synaptic terminals can release neurotransmitter by spontaneous vesicle fusion that is independent of presynaptic action potentials.
• The traditional view of spontaneous neurotransmitter release suggests that spontaneous events occur randomly in the absence of stimuli owing to low-probability conformational changes in the vesicle fusion machinery.
• Recent studies have identified key distinctions between the synaptic vesicle fusion machineries that perform spontaneous versus evoked neurotransmitter release.
• In mammalian hippocampal synapses and at the Drosophila melanogaster neuromuscular junction, spontaneous and evoked neurotransmitter release events show some spatial segregation and activate distinct populations of postsynaptic receptors.
• Segregation of spontaneous neurotransmission enables selective neuromodulation that is independent of evoked release.
• In mammalian hippocampal synapses and at the D. melanogaster neuromuscular junction, spontaneous release events activate specific postsynaptic signal transduction cascades that maintain synaptic efficacy or regulate structural plasticity and synaptic development.
• Novel strategies that selectively target spontaneous release events are needed to address whether spontaneous release can signal independently during ongoing activity in intact neuronal circuits.
• Introduction

Introduction

Our current insights into the mechanisms underlying synaptic transmission originate from experiments that were conducted in the 1950s by Bernard Katz and colleagues. A key aspect of these studies was the discovery of spontaneous neurotransmitter release events, which seemed to occur in discrete 'quantal' packets. This fundamental observation enabled the complex and seemingly intractable nature of action potential-evoked neurotransmission to be analyzed and understood on the basis of its unitary components. Although the original work solely relied on electrophysiological analysis, later studies that used electron microscopy provided visual validation of the hypothesis that neurotransmission occurs through fusion of discrete synaptic vesicles that contain neurotransmitters with the presynaptic plasma membrane.

Read more: The mechanisms and functions of spontaneous neurotransmitter release

Figure 3: Segregation of spontaneous and evoked neurotransmission.

Source: Nature Reviews Neuroscience