Introduction to Kidney Toxicity

Kidney Functions Includes maintaining water balance, pH, excretion of waste, filtering blood, reabsorbing electrolytes, and secreting hormones. Structure Bean-shaped organs located below the liver, 5 key segments apical (superior polar) • superior (meso-ventral superior) • middle (meso-ventral inferior) • inferior (basal or inferior polar) • posterior (retro-pyelic) how many pyramids exist in the renal medulla 7-18 renal parenchyma functional part of the kidney that includes the renal cortex and the renal medulla. function of the renal hilum entry and exit site for structures servicing the kidneys: vessels, nerves, lymphatics, and ureters renal lobe portion of a kidney consisting of a renal pyramid and the renal cortex above it. How many nephrons are in each kidney? about one million what is the capillary bed a system interwoven network of capillaries that supplies an organ. Precapillary sphincters segments of smooth muscle that help direct blood flow to tissues that need it most how many capillary beds make up the portal system two podocytes role preventing plasma proteins from entering the urinary ultrafiltrate by providing a barrier metabolic rate the amount of energy expended by an animal/person/organ/etc over a specific period of time 1/4 Simple cuboidal epithelium is found where lining of nephrons, the walls of the renal tubules Simple cuboidal epithelium role protection, secretion and absorption. When blood oxygen concentration is norscattered cells located predominantly in mal (normoxia), synthesis of erythropoithe inner cortex etin occurs in? synthesis of erythropoietin during hypox- interstitial cells within almost all zones of ia the kidney begin to produce the hormone calcium is the main component of bony skeleton and serves as the intracellular why is calcium homeostasis important and extracellular messenger for neuronal network, immune response, muscle contraction, and hormone secretion. cytochromes P-450 and those enzymes involved in the conjugation of glutathione, glucuronic acid, or sulfate are primarily are localized in ? proximal tubules some isozymes of cytochrorne(s) P450 and glutathione S-transferases are se- thick ascending limb and distal tubules, lectively localized in? prostaglandin H synthase is concentrated in collecting ducts in the medulla. Altered Glomerular Haemodynamics Changes in blood flow dynamics within the glomerulus affecting filtration. what happens when glomerular filtration metabolic wastes will not get filtered from rate is too low the blood into the renal tubules the absorptive capacity of salt and wawhat happens when glomerular filtration ter by the renal tubules becomes overrate is too high whelmed. Tubular Cell Toxicity Harmful effects on kidney tubular cells, impacting their function. ATN Acute tubular necrosis what cause ATN 2/4 lack of blood flow and oxygen to the kidney tissues or kidney cells are damaged by a poison or harmful substance. what does Glycosuria and proteinuria imply potential health issues such as diabetes or kidney damage. oliguria urinary output less than 400 ml per day anuria no urine, or without urine. Inflammation Immune response causing swelling and tissue damage. Crystal Nephropathy Kidney condition caused by crystal deposits in the tubular lumen leading to damage Myoglobinuria Presence of myoglobin in urine due to muscle breakdown. Myoglobinuria causes trauma, alcohol and drug abuse, Thrombotic Microangiopathy Disorder causing blood clots in small blood vessels. Glomerular Filtration Process in the nephron where podocytes prevent plasma proteins from entering urine. Proximal Convoluted Tubule (PCT) Segment of the nephron responsible for reabsorption and secretion. Renin-Angiotensin-Aldosterone System Regulates blood pressure, fluid, and electrolyte balance. Erythropoietin Hormone produced by kidneys to stimulate red blood cell production. Vitamin D Activation Conversion of calcifediol to active vitamin D by renal enzyme. Calcium Homeostasis Maintenance of calcium levels crucial for bone health and cellular functions. Hypocalcaemia Spontaneous opening of voltage-gated ion channels 3/4 Hypercalcaemia Inhibition of voltage-gated ion channel opening Voltage-gated ion channels Integral membrane proteins enabling selective ion passage Parathyroid hormone (PTH) Regulates voltage-gated ion channels Vitamin D Regulates voltage-gated ion channels Prostaglandin H synthase (PGHS) Enzyme in prostaglandin and thromboxane production Nephrotoxicity Damage caused by drugs/toxins to the kidneys NSAIDs Inhibit COX, affecting blood vessel dilation Cyclooxygenase (COX) Enzyme inhibiting prostaglandin synthesis Cadmium Toxic metal accumulating in liver and kidneys Chronic cadmium poisoning Leads to proteinuria Carbon Tetrachloride Causes cellular damage and oliguria/anuria Nephritis Inflammation in kidney tissues affecting waste filtration Glomerulonephritis damage to the tiny filters inside kidneys (the glomeruli), caused by immune system attacking healthy body tissue Interstitial nephritis (the spaces between the kidney tubules become swollen (inflamed) Rhabdomyolysis Destruction of muscle cells leading to myoglobinuria Thrombotic Microangiopathy (TMA) Damaged capillaries causing organ damage Biomarkers of Acute Kidney Injury Indicators like urea, creatinine, and NGAL for kidney damage 4/4