Nephrotoxicology - Toxic Responses of the Kidney Deepmalya Ghosh
Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxins are substances displaying nephrotoxicity.
Nephrotoxicology - Toxic Responses of the Kidney Deepmalya Ghosh
Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxins are substances displaying nephrotoxicity.
The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms.
The term neurotoxicity refers to damage to the brain or peripheral nervous system caused by exposure to natural or man-made toxic substances. These toxins can alter the activity of the nervous system in ways that can disrupt or kill nerves.
The liver plays a key role in detoxifying harmful substances that you may eat, drink, inhale or rub on your skin. Toxic hepatitis is liver inflammation that occurs when your liver is damaged by toxic chemicals, drugs or certain poisonous mushrooms.
The term neurotoxicity refers to damage to the brain or peripheral nervous system caused by exposure to natural or man-made toxic substances. These toxins can alter the activity of the nervous system in ways that can disrupt or kill nerves.
Chapter 12 Chronic Kidney Disease and DialysisKalvinSmith4
For DH Theory III, students must give a presentation on a specific module in the class. The purpose of these presentations is to inform students on how treat patients in a dental setting who may be compromised by a certain medical condition. I was tasked with presenting on chronic kidney disease and dialysis, as well as on sexually transmitted diseases. This is the presentation that I modified on CKD and dialysis.
Respiratory stimulants: types, complete discussion on indications, contraindications, assessment, patient notes and examples of stimulants both central and respiratory
Expectorants and Antitussives: types, complete discussion on indications, contraindications, assessment, patient notes and examples of expectorants and antitussives
Complete pharmacology of Non steroidal Anti inflammatory Drugs, classification, Mechanism of action, Pharmacological actions, Indications, Contraindications, Adverse effects
Pharmacology laboratory experiment, both invivo and invitro includes interpolation, matching , bracketing, three point, four point bioassays with a note on hypoglycemic activity, acute skin irritation, acute eye irritaiton, pyrogen test, gastrointestinal motility test, physiological salt solutions
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
1. TOXIC RESPONSES
OF KIDNEY
RVS Chaitanya Koppala
Assistant professor
Vignan Institute of Pharmaceutical Technology
Visakhapatnam
2. TOXIC RESPONSES OF KIDNEY
The kidneys are the important organs that help maintain body homeostasis by carrying out
excretion of wastes, regulation of ECF volume, maintaining electrolyte composition and
acid base balance
It also causes conversion of vitamin D3 to active form and release of renin, erythropoietin,
vasoactive prostaglandins and kinins. Therefore, any damage caused by toxicants to kidneys
has the potential to cause physiological changes that extend beyond the boundaries of the
organ itself
The damage caused by nephrotoxicants varies depending on the toxic agent and its dose. It
can be mild or severe, reversible or irreversible. Kidneys are susceptible to harmful effects
of toxicants because of the following reasons.
Firstly, kidneys have a rich supply of blood (approx. 25% of the cardiac output). Therefore,
the blood borne toxins will reach kidneys in large amounts.
As kidneys removes water and other substances from the filtrate, any toxicant that is not
reabsorbed becomes highly concentrated in the filtrate and may cause blockages.
When the toxicant is reabsorbed, it gets concentrated in kidney tubular cells and damage
them
Toxicant induced kidney effects are manifested as acute kidney injury, chronic kidney failure,
nephrotic syndrome.
1. ACUTE KIDNEY FAILURE:
Acute kidney failure is a complex disorder characterized by rapid decline in glomerular
filtration rate (GFR) and buildup of nitrogenous wastes in blood ( azotemia) due to
which kidneys fail to maintain electrolytes and acid base balance.
The signs of AKI ranges from acute rise in serum creatinine to acute kidney failure
The cause of AKI can be grouped in 3 categories
A. Prerenal factors: this includes that causes that decrease blood flow to kidney.
Decreased intravascular flow, renal vasoconstriction and low cardiac output fall
under this category
B. Post renal factors: obstruction of ureters or bladder which impede urinary flow.
C. Intrarenal factors: damage to glomeruli, renal tubules, interstitial and renal
vasculature Pathological changes include damage to epithelial cell of S2 and S3
3. segments of proximal tubules, in the thick ascending loop of Henle and the
glomerulus, the endothelial cells of glomeruli and renal vascular cells.
D. Adaptation following tissue injury/ insult: in response to the damage caused by
nephrotoxicants.
Cells that are severely injured undergoes cell death by apoptosis or necrosis.
Cells that are sub lethally undergo repair and adaptation to maintain structural
and functional integrity.
Uninjured cells and those adjacent to the injured area undergo compensatory
hypertrophy, cellular adaptation and proliferation.
As a result of these adaptative mechanism. GFR increase by about 40-60%. This
leads to increase in proximal tubular reabsorption of water and solutes and thus
the renal function is restored.
However, with time this adaptive response become maladaptive as a result of
which focal glomerulosclerosis develops which in turn cause tubular atrophy
and interstitial fibrosis.
2. CHRONIC KIDNEY FAILURE:
It is characterized by decrease glomerular filtration. This condition is progressive and
damage cause is irreversible.
The disease is very slow in its onset, consuming several years and therefore the patients
remains asymptomatic until considerable damage has been done.
Clinical features vary with different stages of chronic renal failure.
a) First stage:
It is called as diminished renal reserve and the most prominent feature of this stage
is that only 25% of the nephrons function normally while the remaining are
irreversible damaged.
However, no symptoms are indicative of renal failure are evident. The reason behind
this is that the 25% nephrons are left and are capable of performing the work done
by the damaged nephrons.
b) Second stage: this stage is characterized by renal insufficiency which in turn is
characterized by reduced GFR. The clinical manifestation includes.
1. Polyuria (passing of large volumes of fluids in urine
2. Metabolic acidosis, caused due to accumulation of H+ ions because of the failure on
the part of the kidney to work as a buffering system.
4. 3. Hypertension
4. Anaemia, due to decrease in renal induced erythropoietin production
5. Increase levels of creatinine and other waste products of protein metabolism.
c) Third stage: it is called the end stage renal failure wherein about 90% of nephron are
damaged. Decrease in number of nephrons occurs along with further reduction in GFR
3. NEPHROTIC SYNDROME:
Nephrotic syndrome is not a renal disorder, but a condition that usually accompanies
other renal diseases.
The most prominent feature of nephrotic syndrome is proteinuria i.e presence of
abnormally large amounts of proteins in urine.
Nephrotic syndrome involves damage to the renal glomeruli resulting in enhanced
permeability of the glomerular membrane.
Due to such change in membrane permeability, the usually conserved proteins get
filtered and are found in urine.
It is also associated with the following.
a) Severe proteinuria: increased permeability of filtration membrane results in
increase transfer of proteins into the glomerular filtrate. The most predominant
proteins lost in urine is albumin because it is most abundant and relatively smaller
in size.
b) Hypoalbuminemia: increased loss of albumin in urine decreases its plasma levels
resulting in hypoalbuminemia. Hypoalbuminemia decrease the osmotic pressure of
the blood.
c) Generalized oedema: reduced osmotic pressure of blood results in marked oedema
which is evident around the eyes, ankles, feet and abdomen.
d) Hyperlipidemia: the actual cause of this manifestation remains unknown.
5. All the clinical features of nephrotic syndrome are dependent upon on another, which is
represented as below
Glomerular damage
↓
Increased permeability of glomerular membrane
↓
High levels of protein gets filtered
↓
Decreased osmotic pressure of blood
↓
Generalized oedema
↓
Decreased renal perfusion
↓
Renin gets secreted which increases the reabsorption of water and electrolytes.
Generalized edema decreases the renal blood flow which stimulate the renin release from the
juxtaglomerular apparatus. Renin stimulates the reabsorption of water and electrolytes which
further decrease the osmotic pressure of blood, thereby worsening the condition.
4. SITE SELECTIVE INJURY:
Based on the site of nephron affected by nephrotoxicants, the kidney injury is divided into
the following types.
a) Glomerulus Injury: within the nephron, glomerulus acts as primary site of chemical
exposure. Nephrotoxicants damage glomerulus in several ways. Few examples are
summarized as below.
6. Toxicant Mechanism of the toxicant
Puromycin Destroy podocytes and thus increases leakage of proteins or cause
separation of podocytes from basement membrane of glomeruli
Gentamicin Increase excretion of anions by decreasing the negative charge of
glomerular membrane
Amphotericin B Decreased GFR by causing renal vasoconstriction
Heavy metals, captopril Interact with immune cells like macrophages, neutrophils and
cause the release of cytokines and reactive oxygen species (ROS)
Cyclosporine Causes renal vasoconstriction, vascular damages and endothelial
cell damage and thus decreases GFR.
GFR may also be decreased by extrarenal factors like ureteral or tubular obstruction.
Decrease cardiac output etc.
Pathological changes include, hypercellularity due to proliferation of cells or
infiltration of WBCs, thickenings of basement membrane, hyalinization and
sclerosis.
b) Proximal tubule injury:
This site, where composition of filtrate is altered, is the main site of action for
nephrotoxicants due to selective accumulation of xenobiotics into this segment.
Chemicals that interfere with renal blood flow, cellular energetic and mitochondrial
function act at this site. E.g. heavy metals, mercury and cadmium
Toxicants may act by damaging the epithelial cells as a result of which membrane
fluidity and calcium homeostasis is disturbed. They may also differ with reabsorption
process leading to glycosuria, amino aciduria and also polyuria (increase in urine
volume). However severe damage to proximal tubule in oliguria (decreased urine
output) or anuria (stoppage of urine flow)
c) Loop of Henle:
After leaving the proximal tubule, the modified filtrate reaches loop of Henle where it
becomes more concentrated counter current mechanism. Toxicants acting at site ( e.g.
amphotericin B, cisplatin, tetracyclines and methoxyflurane) impair the concentrating
ability of the tubule and also cause acidification defects.
7. d) Papillary injury:
Many of the pharmaceutical agents (e.g. NSAIDS) produce damage to the papillary area.
They cause damage to medullary interstitial cells, medullary capillaries, loop of Henle
and collecting ducts. They inhibit the prostaglandins activity and decrease renal blood
flow to capillary area as a result of which tissue ischemia occurs.