01-04-2011, 11:16 AM
Presented by
Harjinder
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NEPHROTOXICITY OF METALS
NEPHRON
Introduction
Nephron is a structural and functional unit of the kidney. Each human kidney contains about one million nephrons
STRUCTURE
It consists of malpighian corpuscle and renal tubule
MALPHIGIAN CORPUSCLE comprises of glomerulus and bowman’s capsule
GLOMERULUS Is consisting of capillaries , blood enters the glomerulus through an affrent areteroile and leaves it through an efferent areteroile. Glomerular filteration takes place in glomerulus.
BOWMAN’S CAPSULE has a double layered cup shaped structure. Two layers are outer parietal layer and inner visceral layer. Parietal layer consists of squamous cells and visceral layer consists of special types of cells called podocytes.
Permeability of glomerular membrane is
100-500 times as greater as that of usual capillary.
1.Proximal convoluted tubule is lined by cuboidal epithelial cells, bearing brush border of tall microvilli.
2.Loop of henle starts at the end of convoluted tubule and major part lies in medulla.It consists of descending and an ascending limb.
3.Distal tubule 4. Collecting duct
TYPES OF NEPHRON ON THE BASIS OF LOCATION:-
1.JUXTAMEDULLARY
Forming 15 % of total
Nephrons, found in
Medulla.
2.CORTICAL Forming 85% of total nephrons. Nephrons.lie in renal
Cortex.loop of henle are
Short.
lie inrenal
FUNCTIONS OF NEPHRON
1.Excretion of metabolic wastes:urea,creatinin.
2.Regulation of extracellular fluid volume,electrolyte composition,acid base balance(PH =7.4±0.5)
3.Synthesis and release of harmones.
4.Metabolism of vitamin D3 to the active 1,25-dihydroxy vitamin D3
GLOMERULAR FILTRATION
A high rate of fluid filtration. Approx 20% of blood entering the Glomerulus is filtered.
selection is made on the Basis of size and charge. Using STARLING EQUATION for capillary filtration describing major determinants of Glomerular filtration rate
Rates of Filtration, Reabsoption and Excretion by the Kidneys
FILTERED REABSORBED EXCRETED REABSORBED
(meq/24h) (meq/24h) (meq/24h) (%)
Glucose (g/day) 180 180 0 100
Bicarbonate(meq/day) 4,320 4,318 2 99.9
Sodium(meq/day) 25,560 25,410 150 99.4
Chloride (meq/day) 19,440 19,260 180 99.1
Water(l/day) 169 167.5 1.5 99.1
Urea (g/day) 48 24 24 50
Creatinine(g/day) 1.8 0 1.8 0
NEPHROTOXICITY
REASONS FOR THE SUSCEPTIBILITY OF THE NEPHRON TO TOXICITY
Kidney receive about 20-25% of the resting cardiac output.
Any drug or chemical in the systemic circulation will be delivered to
these organs in relatively high amounts.
The processes involved in forming a concentrated urine also serve to
concentrate potential toxicants in the tubular fluid.
A nontoxic concentration of a chemical in the plasma may reach to toxic concentrations in the kidney.
Intraluminal precipitation of relatively insoluble compounds, causing ARF secondary to tubular obstruction
Renal transport, accumulation, and metabolism of xenobiotics contribute significantly to the susceptibility of the kidney to toxic injury.
The sensitivity of the kidney to circulating vasoactive substances
VARIOUS POSSIBLE SOURCES OF NEPHROTOXICITY
Metal nephrotoxicity:-Uranium mercury,cadmium
Non steroidal anti inflammatory drugs .
Amino glycoside antibiotics
Radio contrasting dye.
Cisplatin: chemotherapeutic agent.
Halogenated hydrocarbons.
Once a chemical has been identified as a nephrotoxicant in vivo a variety of in vitro techniques may be used to elucidate underlying mechanisms
Perfused kidneys
Kidney slices
Isolated suspensions of renal tubule
Cells or subcellular organelles
Primary cultures of renal cells
Established renal cell lines.