Acute liver failure (ALF) is the rapid deterioration of liver function without preexisting cirrhosis and lasting less than 26 weeks. It is characterized by altered mental status and coagulopathy. Common causes include viral hepatitis, drugs like acetaminophen, poisoning, and ischemia. Evaluation involves detailed history, physical exam, and lab tests. Management focuses on preventing complications like cerebral edema in the ICU while determining candidacy for liver transplantation, the only definitive treatment. Outcomes depend on etiology, with transplantation providing the best chance for survival in severe ALF.
drug induced liver disease
DILD is caused by many different drugs of mostly painkillers and fever reducers which contain acetaminophen drug this is hepatotoxic because drugs are absorbed by liver on high dose of this drug lead damage of liver known as liver injury. Rarely absorbed in children. actually people who drink alcohol has high prone to drug injury, but in children in happened because of antiepileptic and antiniotics.the antibiotics most often implicated with liver injury are amoxicillin/clavulanic acid, flucloxacillin and erythromycin .Nonalcoholic Fatty Liver Disease (NAFLD) is the most common forms of chronic liver disease in children and adolescents. It is an inherited disorder that affects the metabolism – the way the body breaks food down into energy.Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. The culprit drugs in cDILI are similar but not identical to DILI in adults (aDILI). This is demonstrated by recent findings that a drug frequently associated with aDILI (amoxicillin/clavulanate) was rarely associated with cDILI and that the drug basiliximab caused only cDILI but not aDILI. The fatality in reported cDILI studies ranged from 4% to 31%. According to the US Food and Drug Administration-approved drugs labels, valproic acid, dactinomycin, and ampicillin appear more likely to cause cDILI. In contrast, deferasirox, isoniazid, dantrolene, and levofloxacin appear more likely to cause aDILI. Animal models have been explored to mimic children's increased susceptibility to valproic acid hepatotoxicity or decreased susceptibility to acetaminophen or halothane hepatotoxicity. However, for most drugs, animal models are not readily available, and the underlying mechanisms for the differential reactions to DILI between children and adults remain highly hypothetical. Diagnosis tools for cDILI are not yet available. A critical need exists to fill the knowledge gaps in cDILI. This review article provides an overview of cDILI and specific drugs associated with cDILI.
Out of 298 patients enrolled 273 (92%) resolved ⩽1 year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR:1.06, p=0.011], dyslipidemia [OR:4.26, p=0.04] and severe DILI [OR:14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 xULN and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001)
SYSTEMATIC APPROACH TO LIVER FUNCTION TEST
BY Dr. Navas Shareef. P.P (MBBS)
THIS PRESENTATION IS MADE IN A SIMPLIFIED FORM SO THAT EVERYONE COULD UNDERSTAND ABOUT A LIVER FUNCTION TEST EASILY
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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Similar to Acute Liver Failure - Dr. Mutchnick.ppt
drug induced liver disease
DILD is caused by many different drugs of mostly painkillers and fever reducers which contain acetaminophen drug this is hepatotoxic because drugs are absorbed by liver on high dose of this drug lead damage of liver known as liver injury. Rarely absorbed in children. actually people who drink alcohol has high prone to drug injury, but in children in happened because of antiepileptic and antiniotics.the antibiotics most often implicated with liver injury are amoxicillin/clavulanic acid, flucloxacillin and erythromycin .Nonalcoholic Fatty Liver Disease (NAFLD) is the most common forms of chronic liver disease in children and adolescents. It is an inherited disorder that affects the metabolism – the way the body breaks food down into energy.Drug-induced liver injury in children (cDILI) accounts for about 1% of all reported adverse drug reactions throughout all age groups, less than 10% of all clinical DILI cases, and around 20% of all acute liver failure cases in children. The overall DILI susceptibility in children has been assumed to be lower than in adults. Nevertheless, controversial evidence is emerging about children's sensitivity to DILI, with children's relative susceptibility to DILI appearing to be highly drug-specific. The culprit drugs in cDILI are similar but not identical to DILI in adults (aDILI). This is demonstrated by recent findings that a drug frequently associated with aDILI (amoxicillin/clavulanate) was rarely associated with cDILI and that the drug basiliximab caused only cDILI but not aDILI. The fatality in reported cDILI studies ranged from 4% to 31%. According to the US Food and Drug Administration-approved drugs labels, valproic acid, dactinomycin, and ampicillin appear more likely to cause cDILI. In contrast, deferasirox, isoniazid, dantrolene, and levofloxacin appear more likely to cause aDILI. Animal models have been explored to mimic children's increased susceptibility to valproic acid hepatotoxicity or decreased susceptibility to acetaminophen or halothane hepatotoxicity. However, for most drugs, animal models are not readily available, and the underlying mechanisms for the differential reactions to DILI between children and adults remain highly hypothetical. Diagnosis tools for cDILI are not yet available. A critical need exists to fill the knowledge gaps in cDILI. This review article provides an overview of cDILI and specific drugs associated with cDILI.
Out of 298 patients enrolled 273 (92%) resolved ⩽1 year from DILI recognition and 25 patients (8%) were chronic. Independent risk factors for chronicity were older age [OR:1.06, p=0.011], dyslipidemia [OR:4.26, p=0.04] and severe DILI [OR:14.22, p=0.005]. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TB) median values were higher in the chronic group during follow-up. Values of ALP and TB >1.1 xULN and 2.8 xULN respectively, in the second month from DILI onset, were found to predict chronic DILI (p<0.001)
SYSTEMATIC APPROACH TO LIVER FUNCTION TEST
BY Dr. Navas Shareef. P.P (MBBS)
THIS PRESENTATION IS MADE IN A SIMPLIFIED FORM SO THAT EVERYONE COULD UNDERSTAND ABOUT A LIVER FUNCTION TEST EASILY
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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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.
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
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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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!
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
1. Milton G. Mutchnick, M.D.
Professor of Medicine
Chief, Division of
Gastroenterology
Wayne State University
School of Medicine
ACUTE LIVER FAILURE
2. Acute Liver Failure
Rapid deterioration of liver function
resulting in altered mentation and
coagulopathy in a patient without
preexisting cirrhosis and with an illness
of less than 26 weeks duration.
4. Index of Suspicion for ALF
• Clinical signs of moderate to severe
hepatitis
• Laboratory findings including an increase in
the prothrombin time of 4-6sec.(INR ≥ 1.5).
• Altered sensorium
INR ≥ 1.5 + Altered Mental Status = ALF
12. Acute HAV and ALF
• ALF uncommon
• Frequency 0.01% - 0.1% in
jaundiced patients
• ALF occurs early
• Survival (transplant- free) 75%
• Age related survival
13. Acute HBV and ALF
• HBV alone or with HDV co-infection
(rare)
• Transplant-free survival is 23%
• Overall survival 77% because of
transplantation
14. HBV Markers in ALF
IgM Anti HBc 100%
HBsAg 90%
HBV DNA (Abbott) 10%
*Absence of HBsAg favors better
prognosis (47% v 17%).
Higher frequency ALF with mutant
HBV form
15. Drug Induced ALF
• Many drugs implicated
Acetaminophen
Halothone and derivatives
INH/ Rifampin
Tricyclics/ MAO inhibitors
Phenytoin/ NSAID
• Increased risk: acetaminophen (as little as
2gms) + ETOH median dose: 13 gm
• Increased risk if drug continued after
jaundice appears
16. Poisoning and ALF
• Amanita mushrooms (amanatoxins)
- LD = 50 gms (3 mushrooms)
- Toxins not destroyed by cooking
- Rapid onset of HE in 4-8 days
following severe emesis and diarrhea
• Solvents - chlorinated hydrocarbons
• Herbal remedies
• Yellow phosphorus
18. Obstruction of Hepatic Veins
and ALF
• Budd-Chiari syndrome
and thrombosis of hepatic
veins
• VOD - Post BMT
Chemotherapy, Irradiation
19. Massive Malignant Infiltration
of the Liver
• Attributed to ischemic
changes
• Leukemia, lymphoma
• Malignant histiocytosis
• Metastatic Replacement
20. Other Etiologic Causes of ALF
• Wilson’s Disease
can be presenting feature
usually in patients <20 yrs
can occur if patient discontinued
D-penicillamine for a few years
21. Other Etiologies (2)
• Microvesicular steatosis
Acute fatty liver of pregnancy
Reye’s syndrome
Drug Induced - Valproic acid
• AIH
May appear as an acute hepatitis
on initial presentation
More common if anti-LKMI antibody present
ASMA usually not present
22. Other Etiologies (3)
• Hyperthermia (Heat stroke)
Direct thermal injury
Hepatic ischemia due to
-DIC
-Perfusion defect
• OLT
Poor presentation of donor liver
Acute graft rejection
Thrombosis - hepatic artery, hepatic
vein, portal vein
• Partial hepatectomy
Removal of 80% or more of healthy liver
Removal of 50% or less in hepatic dysfunction
24. HISTORY
• Family members with liver disease?
• Recent cold sores
• Onset of jaundice
• Work environment- toxic agents
• Hobbies
• Herbal products/dietary supplements
26. Laboratory Tests
(1)
Drug screening
ALT, AST, Alk Phos, Glu,
Bilirubin
Lytes, Albumin, Mg, Phos.,
CBC with differential
Coags: PT, PTT
Anti HAV IgM
Anti HBc IgM/ Anti HBsAg/
Anti-HCV
27. Laboratory Tests
(2)
If under 35 years of age
Ceruloplasmin
Serum & urine copper
Arterial blood gas
Arterial lactate
Pregnancy test
Autoimmune markers – ANA, ASMA, Ig
levels
HIV status
Amylase & lipase
29. Diagnosis of ALF
Hallmarks - occurs simultaneously or in
succession
• Altered mentation
Clinical
EEG
Arterial Ammonia
• Coagulopathy
PT 4 sec prolonged (INR≥ 1.5)
• Arterial pH<7.3 if acetaminophen ingested
(cause for immediate transfer for OLT)
30. Management of ALF
(1)
• Directed towards prevention of complications
• ICU setting
Central line(s)-10% dextrose
Pulmonary artery pressure and CO
• Inform Transplant Service and transfer with
onset of HE
• Monitor VS and urinary output (Foley)
strict I&O
• Laboratory Testing every 4-6hr
electrolytes, BUN, creatinine, CBC, platelets,
PT, PTT, ALT, AST, T. bilirubin, Alk Phos, Albumin
31. Management (2)
• Maintain gastric pH above 5
- protonix IV
• Preparation for endotracheal intubation
• Prepare to initiate monitoring intracranial
pressure
• Enteral feeding tubes for grade 3 or 4 coma
32. Cerebral Edema
Cerebral Perfusion Pressure
Mean Arterial Pressure – ICP = Cerebral
Perfusion Pressure (CPP)
Ideal ICP<20-25mm Hg Ideal CPP>50-60mm Hg
Imazaki, et al
When CPP<40 for 2 hrs. 0 of 7 patients recovered
When CPP>50 6 of 8 patients recovered
Improved ICP first sign of spontaneous recovery
33. Management (3)
Cerebral Edema & Intracranial Hypertension
(Most serious complications of ALF)
Clinical signs of elevated ICP (Intracranial
Pressure)
-sluggish pupillary response
-increased limb-muscle tone
-none
Monitoring ICP
-usually reserved for grade 3 or 4 coma
-awaiting OLT
34. Management (4)
Cerebral Edema - General Measures
-quiet environment
-elevate head 10°-20°
-avoid sedation (use restraints)
-avoid Valsalva-like maneuvers
-mental status assessments q1-2h
-mannitol if signs of impending
uncal herniation (0.5mg/kg, lolus q4-8h)
when ICP<30-40mm
-assisted ventilation (in all grade 3 and 4)
35. Multiple Organ Failure
Hepatic damage increased risk
of infection
Failure of
clearance
Endotoxemia
Gut leak
MOF Activation of
macrophages
Tissue Circulating Release of
Hypoxia changes cytokines
TNF, IL-1, IL-6
Williams, Sem Liver Dis, Vol 16, No.4, 1996
36. Management (5)
Hemodynamic Complications include:
Hypotension, tachycardia, vascular volume decrease
with capillary leak and vasodilation
•Volume expansion (central line)
•FFP or 4.5% albumin, 10% dextrose
•Maintain pulmonary capillary wedge
pressure 12mm-14mm Hg
•Minimize salt solutions (ascites,
interstitial accumulation)
•Inotropic/pressor support(epi, norepi, dopamine),
but not vasopressin.
37. Management (6)
Coagulopathy/Bleeding Diathesis
• FFP or platelets given in presence of bleeding
• Conventional treatment of GI bleeding
• DIC thrombocytopenia
Metabolic Complications
• Prevent hypoglycemia
• Phosphate and magnesium levels
monitored - replace early
• Enteral feeding, 60gm protein/24 hrs
• No role for high branched-chain AA
• Monitor for lactic acidosis secondary to
tissue hypoxia, sepsis
38. Role of Cardiac Index
(CI = cardiac output/body surface area)
• ALF associated with high CI
• Presence of low CI (<4.5L/min)
is bad prognostic sign
Look for -
blood loss, pneumothorax
lactic acidosis, cardiac tamponade
39. Management (7)
Renal Failure
- In 42% to 82% of ALF
poor prognostic sign
- Rising creatinine and oliguria
- Metabolites of acetaminophen
are nephrotoxic leading to acute
renal failure similar to ATN and
loss of phosphate
-HRS
40. Additional Complications
• ARDS
• Sepsis
- Severe complement deficiency
- Decreased PMN motility
- Decreased Kupffer cell function
and removal of endotoxins
- Increased levels of TNF and IL-6
41. Prognostic Factors
• Dependent on Etiology
• Younger patients do better (<40 and >10)
• Presence of cerebral edema
• Delay between jaundice and HE of more
than 3 weeks - poorer prognosis
• MOF - poor prognosis
46. Approach to Suspected ALF
• Etiology and Pathogenesis
• Evaluation and Diagnosis
• Complications
• Management
• Prognosis
• Current and future treatment
approaches