Hepato Renal Syndrome (HRS) is a form of kidney failure that occurs in patients with advanced chronic liver disease. It results from intense renal vasoconstriction caused by interactions between the systemic and portal circulatory systems. HRS has no underlying kidney pathology and typically develops spontaneously or in response to precipitating events like infections, bleeding, or large volume paracentesis. Diagnosis is based on criteria and HRS carries the worst prognosis of all liver disease complications. Treatment involves terlipressin and liver transplantation provides a definitive cure.
A simple description of a less understood topic in Intensive Care Medicine. Aim to make understanding and management easy for the residents and prevention steps for all ICU workers.
A simple description of a less understood topic in Intensive Care Medicine. Aim to make understanding and management easy for the residents and prevention steps for all ICU workers.
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
hepatorenal syndrome is a one of the complication of cirrhosis of liver. It causes hepatic decompensation of liver. It has high risk of mortality. HRS has two types and type 1 usually present as a acute kidney injury. so, at first HRS should exclude from AKI. HRS type 2 present as a refractory ascites. As this has worst prognosis, only valuable management is liver transplantation.
download link : https://www.dropbox.com/s/xc0fpdul47g1gu8/IgA%20Nephropathy.ppt?m
Join us on our facebook group: NephroTube...............Follow our blog: www.nephrotube.blogspot.com
Dr Abdullah Ansari
PG-2 (Medicine)
AMU ALIGARH
A general approach to periodic paralysis....
(including hypokalemic periodic paralysis and thyrotoxic periodic paralysis, and other “Channelopathies” or “Membranopathies)
Pathophysiology
Epidemiology
Primary or familial periodic paralysis
Secondary periodic paralysis
Conventional classification of periodic paralysis
Classification of primary periodic paralysis based on ion-channel abnormalities
Clinical approach to a case of periodic paralysis
History of muscle weakness
Age of onset
Family history
Timing
Intensity
History of administration of certain drugs
Clinical examination
Differential Diagnosis
Laboratory investigations
Serum K+
CPK and serum myoglobin
ECG
EMG
Nerve conduction studies
Provocative Testing
Muscle biopsy
Treatment
Prognosis
Seminar present the Upper Gastrointestinal Bleeding problems
Edited by : Dr. Inzar Yassen & Dr. Ammar L. Aldwaf
in Hawler Medical Uni. collage of medicine in 14/01/2014
Iraq - Kurdistan - Erbil
basics about chronic liver disease for a pediatrician. fast and easy guide to common causes of chronic liver diseases in children
Please leave a comment if you like it..
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
hepatorenal syndrome is a one of the complication of cirrhosis of liver. It causes hepatic decompensation of liver. It has high risk of mortality. HRS has two types and type 1 usually present as a acute kidney injury. so, at first HRS should exclude from AKI. HRS type 2 present as a refractory ascites. As this has worst prognosis, only valuable management is liver transplantation.
download link : https://www.dropbox.com/s/xc0fpdul47g1gu8/IgA%20Nephropathy.ppt?m
Join us on our facebook group: NephroTube...............Follow our blog: www.nephrotube.blogspot.com
Dr Abdullah Ansari
PG-2 (Medicine)
AMU ALIGARH
A general approach to periodic paralysis....
(including hypokalemic periodic paralysis and thyrotoxic periodic paralysis, and other “Channelopathies” or “Membranopathies)
Pathophysiology
Epidemiology
Primary or familial periodic paralysis
Secondary periodic paralysis
Conventional classification of periodic paralysis
Classification of primary periodic paralysis based on ion-channel abnormalities
Clinical approach to a case of periodic paralysis
History of muscle weakness
Age of onset
Family history
Timing
Intensity
History of administration of certain drugs
Clinical examination
Differential Diagnosis
Laboratory investigations
Serum K+
CPK and serum myoglobin
ECG
EMG
Nerve conduction studies
Provocative Testing
Muscle biopsy
Treatment
Prognosis
Seminar present the Upper Gastrointestinal Bleeding problems
Edited by : Dr. Inzar Yassen & Dr. Ammar L. Aldwaf
in Hawler Medical Uni. collage of medicine in 14/01/2014
Iraq - Kurdistan - Erbil
basics about chronic liver disease for a pediatrician. fast and easy guide to common causes of chronic liver diseases in children
Please leave a comment if you like it..
- Recorded videos of the lecture:
English Language version of this lecture is available at: https://youtu.be/-Ynxvhbcl7U
Arabic Language version of this lecture is available at: https://youtu.be/QpK_toctVlw
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Hepatorenal Syndrome one of the Major Complication of Liver Cirrhosis ( Early detection & Treatment ) .......26/6/2016.....Kafrelshiek University ( Resident Lectures).
Sindrom Hepatorenal (SHR) merupakan komplikasi ginjal pada penderita dengan penyakit hati berat (akut/kronik)
Merupakan AKI tipe prerenal dgn dasar hipoperfusi ginjal
Dr Pradeep Jain - Gastroenterology and Hepatobiliary Surgery Expert
Dr. Pradeep Jain Fortis Hospital
Dr Pradeep Jain has wide experience of Gastroenterology Surgery. He has done his M.S (Surgery) and M.Ch in Gastrointestinal and Hepatobiliary Surgery. Presently leading (Director) the Department of Laparoscopic GI, GI Oncology Surgery in Fortis Hospital, Shalimar Bagh. He graduated from Maulana Azad Medical College, Delhi and completed his MS (General Surgery) from Maulana Azad Medical College and LNJP Hospital. He has done his M.Ch (Gastroenterology & Hepatobiliary Pancreatic Surgery) from G.B.Pant Hospital. His particular areas of expertise are Advance Laparoscopic GI, GI Onco & Bariatric Surgery.
Dr. Pradeep Jain, is an experienced and praised laparoscopic gastrointestinal surgeon. As a pioneer in his field, Dr. Pradeep Jain has performed life-changing surgeries to help patients battle gastrointestinal cancers and dangerous levels of obesity.
A learned and dedicated doctor and a compassionate human being, Dr Pradeep Jain is a well known and popular GI surgeon in North West and fondly known as Trouble shooter in surgical fraternity.
Dr. Pradeep Jain - Gastroenterology and Hepatobiliary Surgery Expert
Dr. Pradeep Jain is well renowned Gastroenterology surgeon having wide experience in Gastrointestinal and Hepatobiliary Surgery. He delivers an accurate diagnosis about Gastroenterology condition which might be eluded by other doctors practicing in the same sphere. Dr. Pradeep Jain aspires to clinical excellence and strongly believes in adopting a kind, friendly and holistic approach to patient care. He sees patients from all walks of life and has a national and international referral practice, a large number of patients have been benefited from the diagnostic and therapeutic endoscopic services so far.
A presentation on the pathology and current management (with Especial emphasis on surgical management) of Portal Hypertension; a common complication of liver cirrhosis among other liver diseases. Being a copy of seminar presentation I for the HepatoPancreaticoBiliary Unit of the Division of General Surgery, Ahmadu Belllo University Teaching Hospital, Zaria.
Atrioventricular blocks are related to delay in conduction of the AV node..
Their recognition is primarily by ECG, anatomical correlation is by EP study.
ST elevation is not always due to STEMI. Other causes to be kept in mind to prevent the undue complications of thrombolysis. wrong patient and wrong management
The electrocardiogram, a basic tool in cardiology has been developed two centuries ago. It was recorded by a giant machine at that time, which is now being recorded on a mobile. Such is the advancement in ECG, which is still the gold standard in diagnosis of VT .
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- 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
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
2. INTRODUCTION
• Hepato Renal Syndrome (HRS) is a functional and reversible
form of renal failure , in patients with advanced chronic liver
disease.
• Interactions between systemic and portal hemodynamics causes
intense renal vasoconstriction .
• May develop spontaneously without known precipitating factors
but there are known triggers.
• To be diagnosed based on criteria.
• Worst prognosis of all the complications of cirrhosis.
• Terlipressin is the drug of choice in treatment.
• Liver transplantation is the definitive cure for patients.
• Recently liver dialysis by means of albumin bound membranes is
providing a means of extracorporeal liver support.
3. History
• Frerichs ,Flint - first report of renal failure in the
absence of significant renal histologic changes,in
chronic liver diseases.
• Hecker, Sherlock (1956) – Pathogenesis of
hepatorenal syndrome.
• Epstein et al - splanchnic ,systemic vasodilation
together with intense renal vasoconstriction is
the pathophyisological hallmark of HRS.
• 1970 s -TERMINAL FUNCTIONAL RENAL FAILURE
• 2007 -Molecular Adsorbent Recirculating System.
5. Case
• A 35-year-old male,k/c/o alcoholic cirrhosis, ascites and a
history of alcoholic hepatitis presented to casualty for
management of his cirrhosis and was diagnosed with new-
onset renal insufficiency upon admission.
• no history of renal dysfunction ,diabetes mellitus. He had
blood transfusions at another hospital 5 days previously after
having suffered a gastrointestinal hemorrhage.
• No h/o SBP or recent treatment with nephrotoxic drugs. Upon
admission, he was taking pentoxifylline 400 mg three times
daily (tid) for alcoholic hepatitis, and furosemide 80 mg daily
(qd) and spironolactone 200 mg qd for his cirrhosis with
ascites.
6. • Physical examination revealed jaundice, ascites, and spider
angiomas on his chest. Viral hepatitis serologies were
negative, but ultrasound revealed a nodular liver and
splenomegaly. No evidence of chronic renal parenchymal
disease or obstructive uropathy. Ascitic fluid analysis
demonstrated a SAAG of >1.1g/dl.
• Diuretics were discontinued, and intravascular volume
replacement was provided by administration of both 1.5 l of
isotonic saline and a total of 120 g of human albumin
administered over several doses but the patients renal
function continued to worsen.
• A DIAGNOSIS OF HEPATORENAL SYNDROME WAS MADE.
7. CAUSES OF RENAL FAILURE IN CIRRHOSIS
H
• Large volume paracentesis Y
• Shock P
O
• Sepsis T
• Nephrotoxic Medications E Renal failure
• Intrinsic renal diseases N
• Volume depletion secondary S
to diuresis. I
O
N
8. Diagnostic Approach to Renal Failure in Cirrhotics
Renal failure in a pt with cirrhosis hold diuretics,offending medications
YES Trial of ntravascularvolumeexpander
ECF fluid losses;rapid/excessive diuretics (albumin)if renal function ↑ses ,
h
Vomiting,diarrhoea,hemorrhage,recent, Diagnosis of prerenal failure is
LVP /hemodynamic changes due to use of made
NSAIDS (or)ACEI YES
NO Toxic or ischemic renal failure
Recent use of nephrotoxicmedications
Hypotension(sepsis,hemorrhage) YES Suspected glomerular disease
NO Depending upon clinical scenario
Glomerular proteinuria&hematuria Further workup may include
i.e.,dysmorphic RBCs and RBC cast Cryoglobulins C3,C4 and renal
NO YES biopsy
Imaging (USG,CT scan)shows Suggestive of obstructive uropathy
Hydronephrosis,urinary retention Unless long standiing relief of obstruction
NO Should lead to improvement in
YES renalfunction
Patient has evidence of Portal
Diagnosis of HRS can be
Hypertension & serum
made
creatinine>1.5mg/dl
9. IAC verbatim
• “Hepatorenal syndrome is a syndrome that occurs in
patients with chronic liver disease, portal
hypertension and advanced hepatic failure .It is
characterised by impaired renal function, marked
abnormalities in arterial circulation and activity of
endogenous vasoactive systems . In the kidney ,there is
marked renal vasoconstriction that results in low
GFR. In the extrarenal circulation there is
predominance of arteriolar vasodilation , that results
in reduction of total systemic vascular resistance and
arterial hypotension.A similar syndrome may also
occur in the setting of acute live failure”.
-IAC ,Chicago 1996
10. DEFINITION
• First systemic attempt to define HRS was made by
International Ascites Club(1994)
• HEPATORENAL SYNDROME is a distinct form of
fucntional acute/sub acute renal failure charecterised by
severe renal vasoconstriction which develops in
decompensated Cirrhosis or Acute liver failure,in the
absence of uderlying renal pathology. (Clinics of
North America;Expert consensus;1996)
• Recently updated to include Albumin as volume
expander.
11. EPIDEMIOLOGY
• Incidence of HRS in patients with chronic liver disease is not
well studied.
• 4% of patients admitted with decompensated cirrhosis.
• In a study of 234 non azotemic patients with liver disease who
had ascites and cirrhosis,18% developed HRS at 1year and
39% developed by 5 years.
• Retrospective studies indicate HRS is present in 17% of
pts admitted to hospital with ascites,and in > 50% of
cirrhotics dying from liver failure
• Some patients without ascites devolped the condition in the
setting of acute fulminant hepatic failure.
12. Pathophysiology
• Four interrelated pathways have been implicated in the
pathophysiology ..
• “Possible impact of each one of
these pathways on renal
vasoconstrcition and development of
HRS varies from one patient to
other .”
• 1.PERIPHERAL ARTERIAL VASODILATION
• 2.STIMULATION OF RENAL SNS
• 3.CARDIAC DYSFUNCTION
• 4.CYTOKINES ,VASOACTIVE MEDIATORS.
13. Cont..
• 1.PERIPHERAL ARTERIAL VASODILATION :
• Rational and simple explanation to the hemodynamic
changes that takes place in cirrhosis ,HRS.
• Degree of hepatic decompensation degree
of hyperdynamic circulation ,
• Degree of hepatic decompensation 1/
arterial BP.
• Reversal of HRS ,improvement of hemodynamics by
systemic vasoconstriction gives support to this
hypothesis.
14. Pathophysiology of HRS
CIRRHOSIS
splanchnic arterial vasodilation
arterial underfilling
stimulation of systemic vasoconstrictors
renal vasoconstriction
late stage of cirrhosis early stages of cirrhosis
local vasodilators , local vasoconstrictors systemic and local
vasodilators
HEPATORENAL SYNDROME PRESERVED RENAL PERFUSION
15. Correlation between clinical features and
pathophysiology in HRS
HRS
diuretic refractory
ascites
ascites
Clinical
Physiological
Portal HTN
Splanchnic vasodilation
renal vasoconstriction
16. • 2.stimulation of renal SNS :
• sympathetic tone in pts with cirrhosis.
• KOSTREVA et al vena caval ligation -- increased
intrahepatic pressure -- renal sympathomimetic
activity --wears after anterior hepatic nerves are cut.
• Severing renal ,hepatic,spinal nerves abolishes the
response of decreased GFR ,RPF seen after
hepatocyte swelling.
17. • 3.cardiac dysfunction :
• Myocardial contractility impaired.( cirrhosis )
• Diastolic dysfunction cirrhosis progression
• Hyperdynamic state being present
• Cause is diseased liver ,reversible after TRx
• BNP , CVP child pugh score ,ventricular wall
thickness.
• Neurohormonal activity - growth ,fibrosis – disturbed
relaxation .
• Inhibitory effect of TNF ,NO on ventricular function.
19. • 4.cytokines ,vasoactive mediators:
• Not a sole player.
• NO,TNF ,endothelin , endotoxin,glucagon,increased PG s .
• Upregulation of e NOS activity,endotoxin ,inducible.
• Reduces pressor effect of vasoconstrictors.
• More in cirrhotics ,ascites.
• Renal vasoconstriction due to dimethylarginine - a natural
NO inhibitor.
• Reduced cyclooxygenase activity in renal medullary tissue.
20.
21. Precipitating factors
• In type I HRS ppting event identified in 70-100 % pts.
• More than one event in a patient.
• Bacterial infections
• Large volume paracentesis without albumin infusion.
(15%)
• GI bleeding
• Acute alcoholic hepatitis. (25%)
• SBP - 20-30% develop HRS.
22. How ppt factor leads to renal failure?
• A.cytokine-induced aggravation of the circulatory
dysfunction with further stimulation of the RAAS and SNS and
worsening renal vasoconstriction.
• intrarenal vicious cycle that favors more renal vasoconstrictor
release and impairs renal vasodilator synthesis .
• will progress to HRS even if the underlying precipitating event
has been corrected.
• B.secondary to deterioration in cardiac function as a result of
either the development of septic cardiomyopathy or
worsening of a latent cirrhotic cardiomyopathy
23. DIAGNOSIS OF HRS
• Diagnosis of HRS is made on certain predefined
criteria in the appropriate clinical setting
• Increasing s.creatinine in patients with cirrhosis and
acute fulminant liver failure itself is enough to
investigate for Hepatorenal syndrome
• All the major criteria are to be met
for the diagnosis of HRS and minor criteria
are just supportive and are not essential to
make the diagnosis
24. MAJOR DIAGNOSTIC CRITERIA
1)Chronic/Acute liver disease with advanced hepatic failure or
portal hypertension
2)Serum creatinine >1.5mg/dl(reflecting decreased GFR),<40
ml/min
3)Absence of shock,bacterial infection,current or recent
treatment with nephrotoxic drugs,absence of renal or g.i.t
losses
4)No increase in renal function after diuretic withdrawal and
plasma volume expansion and intravenous albumin(1g/kg bdy
wt upto a maximum of 100g)
5)Proteinuria <500mg/dl, no USG evidence of renal
parenchymal damage (urine analysis) , no obstructive
uropathy.
25. MINOR DIAGNOSTIC CRITERIA
Urine volume <500ml/24 hr
Urine sodium <10 meq/L
Urine plasma osmolality greater than plasma osmolality
Urine blood cells<50 per HPF
Serum sodium <130 meq/L
26.
27. CLASSIFICATION OF HRS
Classified based on TIME COURSE and PRECIPITATING
FACTORS
Four types-
HRS type-1: Cirrhosis with rapidly progressive acute renal
failure
HRS type-2:Cirrhosis with sub acute renal failure
HRS type-3:Cirrhosis with type-1 or type-2 HRS
superimposed on chronic kidney disease/acute renal
injury
HRS type-4:fulminant liver failure with HRS
Clinics of North America,2006
28. TYPE-1 HRS
It is the cirrhosis with rapidly progressive acute renal failure
Characterized by-
Rapid elevation of BUN and creatinine:100% increase with a level
reaching 2.5mg/dl in 2 weeks or a 50% reduction in initial 24 hr
clearance to < 20 ml/min
Rapidly progressive
Mortality reaching 80% with 2 weeks
Commonly has precipitating factors-SBP(20%)
-variceal hemorrhage
-acute alcoholic hepatitis
-drug induced(acetaminophen)
-acute hepatic injury from viral hepatitis
Deeply jaundiced ,coagulopathy
Death by hepatic plus renal failure,variceal bleeding.
29. TYPE-2 HRS
Cirrhosis with sub acute renal failure
Characterized by-
Slowly increasing serum creatinine levels and slow
reduction of GFR(Takes weeks to months)
No precipitating factor
It has poorer prognosis and eventually progresses to type -1
due to precipitating factors
30. TYPE-3 HRS
Cirrhosis with type 1 or type 2 HRS superimposed on
chronic kidney disease or acute renal injury
85% of end stage cirrhotics have intrinsic renal disease
on renal biopsy
Diagnostic markers of HRS are absent
31. TYPE-4 HRS
Fulminant liver failure with HRS
More than 50% of acute fulminant liver failure develop
HRS
Prognosis of HRS is superimposed on already poor
prognosis of acute fulminant liver failure.
32. CLINICAL FEATURES
• SYMPTOMS-
-distension of the abdomen
-change in mental status(confusion,delirium and
dementia)
-coarse muscle movements or muscle jerks
-dark coloured urine
-yellow skin
-↓sed urine output
-nausea and vomiting
-weight gain
34. DIFFERENTIAL DIAGNOSIS
• Pre renal causes--- hemorrhage ,diarrhea,hypovolemia
• Intra Renal causes --- acute tubular necrosis,interstitial
nephritis.
• Post renal causes -- uropathy
• Diagnosis by exclusion.
• it is extreme example of prerenal failure.(Una <20 ,Fna <1,
Ucr/Pcr >40 ,Uosm/Posm >1.5 )
35. LABORATORY STUDIES
• Diagnosis depends mainly on s . creatinine levels as no
specific tests establish the diagnosis of HRS. (>1.5mg/dl)
• Though serum creatinine level is a poor marker of renal
function in cirrhosis (low muscle mass)
no other validated and reliable non invasive markers exist for
monitoring renal function in these patients.
• Inulin clearance is cumbersome and is not used clinically.
• Low GFR is defined by s cr >1.5 mg/dl without diuretic
therapy for at least 5 days.
• overestimates GFR by upto 50% .
36. CBP ,WBC : infection such as SBP if leucocytosis or bands are
present,a condition known to present with reversible
impairment in renal function
Serum electrolytes and renal function
Liver function test with PT (although the degree of liver failure
doesn’t correlate with the development of HRS,these are
essential for Child-Pugh scoring)
Blood cultures- for bacteremia particularly if no precipitant is
identified,is prudent( 20% SBP are culture -ve)
Cryoglobulins- in patients with hepatitis B and or C who can
develop renal failure from cryoglobulinemia.
37. MANAGEMENT
GENERAL MANAGEMENT:
• Type I HRS - hospitalization, type 2 - outpatient.
• CVP for assessing fluid status.
• Stop diuretics
• Tense ascites -paracentesis
• If > 5l of fluid removed ,then albumin is good as
volume expander.
• low salt diet,free water restriction -hyponatremia cases.
• HRS type-1 & 4 need intensive management
39. Pharmacological treatment
• Goal : reverse renal function
• Prolong survival until liver TRx.
• 1.RENAL VASODILATORS
• 2.SYSTEMIC VASOCONSTRICTORS.
• 1.RENAL VASODILATORS:
• DIRECT renal vasodilators - DOPAMINE,FENOLDOPAM,PGs
• Antagonizing endogenous effect of renal vasocontrictors-
Sarlasin,ACEI ,endothelin antagonists.
40. DOPAMINE
Low dose dopamine(2-5µgm/kg /min) is prescribed in the hope
that its vasodilatory properties may improve renal blood flow
MISOPROSTOL
A synthetic analogue of PG E1, use was based on the
observation of low urinary levels of vasodilatory PGs.
The use of both the above drugs was not substanciated by any
studies
RENAL VASOCONSTRICTOR ANTAGONIST
Sarlasin used in attempt to reverse renal vasoconstriction.
This inhibits the hemostatic response to hypotension and led to
further worsening of renal function .
N-ACETYLCYSTEINE
Mechanism of action is unknown but studies encourage
optimism for medical management where option for liver
transplant is not present
41. • None of the studies that used renal vasodilators showed
imrpovement in renal perfusion or GFR. -- Barnado et al
, Benette et al .
• Because of adverse effects
,lack of benefit the use of
renal vasodilators has been
abandoned.
42. Systemic vasoconstrictors
• Most promising agents.
• Interruption of splanchnic vasodilation will relieve the
intense renal vasoconstriction.
• VASOPRESSIN ANALOGUES -ORNIPRESSIN ,TERLIPRESSIN
• SOMATOSTATIN ANALOGUE -OCTREOTIDE.
• ADRENERGIC AGONISTS - MIDODRINE, NOREPINEPHRINE.
43. VASOPRESSIN ANALOGUES:
• Marked vasoconstrictor effect.
• V1receptors on smooth muscle of arterial wall .
• Rx of acute variceal hemorrhage.
• Ornipressin -- ischemic adverse effects. (30% )
• Terlipressin – most common used drug now.
• Better response in type 2 HRS than in type 1 HRS.
• 17-50% recurrence rate of HRS. – reversible.
• Duration of therapy is unclear.
• 60-80% improvement in type IHRS
• To be given until s creatinine< 1.5 mg/dl ,or 15days.
• Liver disease occurs in 3 months of therapy if not TRx.
44. OCTREOTIDE:
• An inhibitor of glucagon.
• Ineffective in type 2 HRS
Alpha ADRENERGIC AGONISTS - MIDODRINE,NE
• Both are ineffective in type 2 HRS .
• Better response in type I HRS.
DRUG DOSE DURATION SIDE EFFECTS
TERLIPRESSIN 0.5-2mg every 4 hrs as 15 days Peripheral,cardiac,splanchnic
IV bolus ishemia
NOREPINEPHRINE 0.5-3.0 mg/hr IV 15 days same
infusion
MIDODRINE 7.5-12.5 mg every 8 hrs ?? Not reported
oral
45. • High HRS recovery rate with
vasopressin and improved survival
,more likely to recieve a liver
transplant compared to octreotide -
Kiser et al.
• Norepinephrine role is paradox -
levels are elevated in pts with
HRS.Significant improvement with
46. TREATMENT PROTOCOL
OF NORADRENALINE/TERLIPRESSIN PLUS AIBUMIN FOR HRS:
• NA –Initial dose 0.146µg/kg/min iv infusion,if no increase in
MAP by 10mm Hg, dose by 0.05µg/kg/min every 4thhrly up
to dose of 0.7µg/kg/min
• Terlipressin- 1mg iv bolus every 4th hrly.At day 3 if baseline
s. creatinine not reduced ≥25% , the dose up to 2mg every
4thhrly
47. MIDODRINE WITH OCTREOTIDE
Midodrine(alpha adrenergic blocker) and octreotide
(somatostatin analogue)
Rx protocol of midodrine plus octreotide therapy
Octreotide
initial dose:100µgm t.i.d SC
goal to increase upto 200µgm t.i.d SC
Midodrine
Initial dose:5mg,7.5mg,10mg t.i.d orally
goal to ↑dose upto 12.5mg to 15mg t.i.d if necessary
Because of oral and subcutaneous route of the drug
suitable for use in outpatient deparment
49. TIPS
• Insertion causes reduction of portal pressure.
• Beneficial in patients with cirhhosis and refractory ascites.
• M.O.A- suppression of putative hepatorenal reflex,
improvement in circulatory volume,ameiloration of cardiac
function.
• Guevara et al
• Unanswered observations
• 1 . Parameters improve,but not normalize. After TIPS.
• 2.maximum renal recovery is 2-4 wks.
• 3.advanced cirrhotic patients are not benefited.
• 4.ppts underlying acute heart failure.
50. TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT(TIPS)
Is theoretically attractive therapy
It dramatically lowers portal pressure leading to ↓ pooling of
blood in splanchnic bed
But ↑venous return is inappropriately handled
And many patients do not meet the criteria for TIPS
insertion(i.e serum bilirubin <5mg/dl,INR <2 and Child-Pugh
score <12)
When these conditions are not met TIPS insertion may lead to
liver failure or intractable hepatic encephalopathy
Done only in patients with Child-Pughs A/B with criteria and
who do not respond to vasoconstrictor therapy
Patients with refractory ascites often proceed to the
development of HRS type -2 and TIPS in these patients may
lead better survival(metaanalysis)
51. SURGICAL CARE
PERITONEOVENOUS SHUNTING
theoretically seems attractive because it leads to plasma
volume expansion and improvement of circulatory
function
Has no role in type-1 HRS
Important for patients type-2HRS who have refractory
ascites and are not candidates for orthotopic liver
transplant and do not tolerate frequent LVPs
52. ARTIFICIAL LIVER SUPPORT
Eliminates circulating mediators of splanchnic
vasodilatation & renal vasoconstriction
Provides hemodynamic benefit and decreases s. creatinine
Continous venovenous hemofilteration is better.
In Acute liver failure patients treated with porcine
hepatocyte based bioartificial liver reported renal failure
no details provided
Currently these are being used in HRS but are not
advocated for its treatment.
53. ALBUMIN DIALYSIS
• Currently three systems are available for albumin dialysis.
• 1.MARS
• 2.PROMETHEUS
• 3.SINGLE PASS ALBUMIN DIALYSIS (SPAD)
54. MOLECULAR ADSORBENT RECIRCULATING
SYSTEM (MARS)
• Designed by Stange and Mitzner from Germany in 1993.
• Cell free ,modified dialysis technique.
• Three circuits - blood,albumin,renal.
• 600 ml of 20% albumin acts as dialysate
• Removes both albumin bound,water soluble substances by
using a combination of albumin enriched dialysate,CRRT.
• Removal of albumin bound bile acids (detrimental to
hepatocytes) ,kidney –stabilizes liver function.
• Removes water soluble TNF A , IL6 and NO.
• Substance . 50 KDa are not removed .
Artif Organs 1993 ;17:809-13
55.
56. PROMETHEUS
• First described in 1999 .
• Principle of fractioned plasma seperation and adsorption.
• Albumin permeable membrane ,size of 250kDa.
• Albumin passes through the membrane and adsorbers that
remove toxins.
• Reduction of both bilirubin,urea more > MARS.
Rifai K, Kretschmer U ,et al. J.Hepatol 2003 ; 39:984-90
57. SINGLE PASS ALBUMIN DIALYSIS(SPAD)
• Dialyses blood/plasma against a 4.4% solution of
albumin,disposed after a sinlge pass.
• A standard renal replacement machine is used with out any
additional perfusion pump system
• With regard to bilirubin,ammonia it is greater than MARS in
its detoxifying capacity.
• In vivo useful in fulminant hepatic failure.
• Further experience required for routine use.
Kreymann B, Schweigart U et al. J.Hepatol 1999;31:1080-5
58. RENAL REPLACEMENT THERAPY
• Controversial role in pts with type I HRS ,not undergoing
liver TRx.
• To be individualized.
• Indications:
• 1.waiting for liver TRx
• 2.developed volume overload
• 3.intractable metabolic acidosis.
• 4.hyperkalemia.
• Bridge to liver TRx.
• CRRT > HD - removes inflammatory cytokines - TNF A,IL-6
• FUTILE IN pts on mechanical ventilator.
59. LIVER TRANSPLANTATION
• Best treatment for suitable patients with HRS.
• RENAL SODIUM excretion,hemodynamic abnormalities
normalize in 1 month.
• Renal resistance index normalize in 1 year post
transplantation.
• Allocation is by MELD score.
• Alessandra et al MELD score not beneficial for HRS pts.
• Prolonged hospitalizations required
• Renal failure persists for weeks post TRx.
• Post TRx reversal of HRS is 58%.
60. LIVER TRANSPLANT
Long term survival following liver transplant is good
Mortality of individuals with HRS was as high as 25% within the
first month after transplantation(HRS patients with grater
hepatic dysfunction MELD score >36 are at greater risk of
early mortality)
high priority is given to type-1
But these patients are not transplanted because of the
precipitating event which initiated HRS and are extremely ill
with multiorgan failure and rapid course of the disease
providing insufficient time
61. In patients with HRS type -2 liver transplant is more
practical because of the absence of precipitating
factors,longer clinical course & less severe renal failure
In type-3 HRS both liver and kidney transplant in these
extremely ill patients is a dilemma.
only liver transplant may be beneficial given the
prospect of post op RRT
Patients with low MELD score and successful
vasoconstrictor therapy have lower post op
complications.
Further deterioration of renal function after liver
transplantation is transient and is thought to be due to
use of immunosuppressants that are
nephrotoxic(tacrolimus, cyclosporin)
62. Renal function before
liver TRx is an independent
predictor of both short
term and long term post
transplantation patient and
graft survival…Gonwa et al
63. Predictors of renal recovery
• Younger recipients
• Nonalcoholic liver disease
• Low posttransplantation bilirubin
• Age of the donor
64. LKT
• Prolonged duration of RRT pretransplantation.
• h/o previous renal failure
• CKD on biopsy.
65.
66. SPECIFIC THERAPY
TYPE OF HRS TREATMENT
TYPE I HRS Vasoconstrictors,albumin,TIPS,liver Trx
TYPE 2 HRS Vasoconstrictors ,LVP,TIPS(ref),Liver
Trx
TYPE 3 HRS CRRT, LKT
TYPE 4 HRS idealy LTx
67. PREVENTION
Prompt treatment of precipitating factors of type-1
HRS like sepsis, shock, variceal hemorrhage,acute
alcoholic hepatitis and nephrotoxic drugs according
to standard guidelines
A trial has shown norfloxacin as prophylaxis for SBP
decreases HRS to 28% compared to 41%
Albumin administration at diagnosis and day 3 in
patients with SBP decreases HRS. (10%)
Pentoxyphylline 400mg tid for 28 days in alcoholic
hepatitis decreases HRS.( 24%)
However these are not proved in recent studies
68. prognosis
• Worst prognosis of all complications of cirrhosis.
• Type 1 HRS without Rx < 2 weeks
• All pts in 8-10 weeks after onset of RF.
• Type 2 HRS - 6 months .
Lancet 2003 ;362:1819-1827
69. Unanswered questions….
• 1.best modality of therapy
• 2.predictability of LKT versus a liver only transplant.
• 3.how are vasoconstrictors compare with TIPS,MARS
• 4.best to use vasoconstrictor?
• 5.whether there is an independent beneficial effect of
albumin in HRS?
• 6.why renal recovery rate is variable between centers.
70. TRIALS
Fabrizi F et al – meta analysis (2007) of terlipressin therapy for
HRS
Sanyal A,boyer T,Teuber P(2007)-Randomised double blind
placebo controlled trail for terlipressin therapy
In both the trials showed that terlipressin is more effective than
placebo in reversing HRS
Nakaeh,Igarashi T,Tajimi K et al-case report of hepatorenal
syndrome treatment with plasma differentiation(2007)
Rimola A,Navasa M,Grande et al-liver transplantation for
cirrhosis and ascitis(2005)
71. Take home message
• 1.HRS is a functional reversible renal
failure in cirrhotic, fulminant liver failure
patients.
• 2. patients with SBP ,who underwent LVP
, had GI hemorrhage should be carefully
followed up as they are more prone for
HRS.
• 3 .diagnosis by exclusion ,based on major
criteria.
• 4.type I HRS has high mortality ,HRS 2
prolonged survival ,type3 in CKD ,type 4
HRS - fulminant hepatic failure.
72. • 7.MARS is an upcoming procedure.
• 8.Liver TRx is treatment of choice .
• 9.MELD score does not work out for
HRS patients
• 10.recovery depends on age,s
bilirubin,non alcoholic liver disease.
• 11.role of LKT in patients with HRS to
be checked out.
• 12.albumin infusion in patients with SBP
73. REFERENCES
• MEDICINE UPDATE ,vol 17 , 2007
• HEPATORENAL syndrome :pathophysiology and management
:Amercian Society Of Nephrology ,2006
• Emedicine .com
• Clinics of North America ,2006,2007 – care of cirrhotic patients
,hepatic emergencies in cirrhosis.
• Mayoclinic.com
• HARRISON’S PRINCIPLES OF INTERNAL MEDICINE ,18th ed
• World journal of gastroenterology ,2007:4046-4055,