ENDOCRINE FUNCTIONS OF THE KIDNEY

 

Many substances with biological activity are synthesized in the kidney and exert either paracrine (functions of transport, metabolic conditioning, or the growth of renal cells) or systemic (endocrine).

Vitamine D

The active form of vitamin D [1, 25 (OH) 2– vitamin D 3 or calcitriol] is produced in proximal tubular cells from its hepatic precursor, 25 (OH) vitamin D3, under the influence of alpha-hydroxylase. This enzyme's activity is increasing. PTH released by PTH increases the activity of this enzyme... The active form of vitamin D raises digestive and renal absorption of calcium and intestinal absorption of phosphate.

Erythropoietin (EPO)

It is a glycoprotein produced by interstitial peritubular fibroblast cells in response to changes in partial tissue pressure of O2. In addition, EPO is produced in response to cellular hypoxia, physiological (altitude), or pathology (respiratory pathologies, for example) and stimulates the bone marrow production of red blood cells.

Renin-Angiotensin-Aldosterone System (RAAS)

The renin secreted at the juxtaglomerular apparatus in response to changes in blood volume, proteolytically active circulating angiotensinogen of hepatic origin; the converting enzyme converts the released angiotensin I into angiotensin II (Figure 6). Muhammad Khan provides the best nephrology doctors in Riverside.  The angiotensin II exerts potent vasoconstrictor effects (via the AT1 receptor) and stimulates the secretion of aldosterone adrenocortical, promoting retention of Na and secretion of K + and H +. The stimuli of renin secretion are volume depletion or low blood pressure, the sympathetic nervous system.

The increase in sodium chloride concentration in the macula densa (= tubuloglomerular feedback).

The inhibition of RAAS by drugs acting at different levels of the activation cascade (FIG. 7) is widely used in the clinic (hypertension, heart failure, progression of nephropathies).

Divers

Endothelin is a peptide produced in the kidney by endothelial cells, mesangial and tubular cells; it is the most potent vasoconstrictor peptide known. PG prostaglandins: the main effect of PGs is to modulate the action of certain hormones on renal hemodynamics or tubular transport. PGs are produced primarily by the medullary collecting duct and interstitial cells, and to a lesser extent, in the cortex by mesangial and glomerular arteriolar cells.

Some are:

Ø  vasodilator and hypotensive (prostacyclin);

Ø  Others have a vasoconstrictor effect (thromboxane).

Growth factors (Epidermal growth factor, HGF, IGF-1) are produced in the kidney; they are involved in the growth of tubular cells.

The renal kinin-kallikrein system is vasodilatory and increases renal blood flow but decreases renal resistance and does not modify glomerular filtration. The effects of kinins are potentiated by ACE inhibitors which prevent their degradation.

Renal catabolism of peptide hormones:

Ø  Ü the filtered peptides and small proteins are degraded by the tubular cells. This tubular catabolism participates in the regulation of hormonal activity; it also makes it possible to avoid the net loss of amino acids which would result from their urinary leakage;

Ø  Ü the plasma concentration of certain polypeptide hormones (insulin) can thus rise during renal failure, following an increase in their lifespan.

Conversely

·         Reabsorption of NaCl in TCD lowers urinary osmolality to a minimum of 60 to 100 mOsm / kg water. Downstream, in the absence of ADH, the collecting channel is impervious to water; the urine eliminated then has a very low osmolality. ADH causes the insertion of aquaporins-2 into the cells of this segment; due to the osmotic gradient between the interior of the tubule and the interstitium, an osmotic flow of water is then created from the tubule to the interstitium. By inhibiting the reabsorption of Na in the loop of Henle, Loop diuretics limit the establishment of the cortico-papillary gradient and, therefore, the kidney's ability to concentrate urine (impaired concentration power). Conversely, thiazide diuretics, by inhibiting Na's reabsorption in TCD, limit the kidney's ability to dilute urine (dilution function disorder), exposing the risk of hyponatremia in case of high water intakes.

·         The activating mutation of the sodium channel subunits has been identified as being responsible for Liddle syndrome, which produces a picture of primary hyperaldosteronism with arterial hypertension, hypokalaemia, and low aldosteronemia, very sensitive to amiloride but resistant to competitive inhibitors of aldosterone.

Fragments of immunoglobulins and albumin

Most of the filtered proteins are reabsorbed downstream in the renal tubule; their concentration in the final urine is less than 200 mg / L. Physiological proteinuria appears to consist in equal parts of proteins of plasma origin (fragments of immunoglobulins and albumin) and of the Tamm-Horsfall protein, a mucoprotein produced by the cells of the loop of Henle.

Permselectivity

Negatively charged basement membrane glycoproteins confer charge selectivity that changes the diffusion of seized substances (permselectivity). Glycoproteins (nephrin, podocin) present in the filtration spaces determined by the pedicels limit the passage of the most prominent proteins. The quantities transported depend on the number of units available; transport is therefore limited and saturable. The increase of the amount of a substrate beyond a threshold (Tm or maximum transport capacity, generally of the order of 10 mmol / L for glucose, 27 mmol / L for bicarbonates) or impairment of the function of this segment will lead to the appearance in the urine of an abnormal quantity of this substrate: glycosuria, bicarbonaturia, aminoaciduria reflect proximal tubular damage, which can affect all transport systems (Fanconi syndrome, complete or incomplete). The quantities transported depend on the number of units available; transport is therefore limited and saturable. Doctor Muhammad Khan provides the best nephrology physicians in Riverside. The increase of the amount of a substrate beyond a threshold (Tm or maximum transport capacity, generally of the order of 10 mmol / L for glucose, 27 mmol / L for bicarbonates) or impairment of the function of this segment will lead to the appearance in the urine of an abnormal quantity of this substrate: glycosuria, bicarbonaturia, aminoaciduria reflect proximal tubular damage, which can affect all transport systems (Fanconi syndrome, complete or incomplete).