Hypokalemia, Hypoxic Ischemic Encephalopathy, Nosocomial Pneumonia and Urinar...Jack Frost
Hypokalemia, Hypoxic Ischemic Encephalopathy, Nosocomial Pneumonia and Urinary Tract Infection.This presentation contains real names of persons involve of this particular study. This names should not be copied or rewritten. Used the data of this study as basis only. All rights reserved 2009.
Debate: Neurocritical Care Improves Outcomes in Severe TBISMACC Conference
Martin Smith and Mark Wilson debate whether neurocritical care improves outcomes in severe TBI.
Martin argues in favour of neurocritical care.
He concedes that longstanding and established practices are not as efficacious or innocuous as previously believed.
Very few specific interventions have been shown to improve outcomes in large randomised controlled trials. With the possible exception of avoidance of hypotension and hypoxaemia, most are based on analysis of physiology and pathophysiology.
Further, the substantial temporal and regional pathophysiological heterogeneity after TBI means that some interventions may be ineffective, unnecessary, or even harmful in certain patients at certain times.
Martin however, contends that improved understanding of pathophysiology and advances in neuromonitoring and imaging techniques have led to more effective and individualised treatment strategies. Ultimately, this has led to improved outcomes for patients.
In particular, the sole goal of identifying and treating intracranial hypertension has been superseded by a focus on the prevention of secondary brain insults. This is done by using a systematic, stepwise approach to maintenance of adequate cerebral perfusion and oxygenation.
Similarly, multimodal neuromonitoring also gives clinicians confidence to withhold potentially dangerous therapy. Particuarly in those with no evidence of brain ischemia/hypoxia or metabolic disturbance.
Mark Wilson on the other hand argues there is no benefit in neurocritical care following severe TBI.
The New England Journal of Medicine has published several articles that demonstrate no benefit from classic neurotrauma interventions (ICP monitoring, cooling, decompression). This is because factors such as ICP and CPP associate with bad outcomes by association rather than causation.
This debate will demonstrate that critical care just complicates things. Evidently, it is high time for the randomised trial between the very best neurocritical care and NOB therapy (Naso-pharyngeal, Oxygen and a Blanket).
Join Martin and Mark as they discuss the pros and cons of neurocritical care in the management of severe TBI.
For more like this, head to our podcast page. #CodaPodcast
Hypokalemia, Hypoxic Ischemic Encephalopathy, Nosocomial Pneumonia and Urinar...Jack Frost
Hypokalemia, Hypoxic Ischemic Encephalopathy, Nosocomial Pneumonia and Urinary Tract Infection. This presentation contains real names of persons involve of this particular study. This names should not be copied or rewritten. Used the data of this study as basis only. All rights reserved 2009.
Management of hypoxic ischemic encephalopathy (HIE) by Sunil Kumar Dahasunil kumar daha
Please find the power point on Management of hypoxic ischemic encephalopathy (HIE) . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
Research guru and PI for the ARISE study, college examiner and semi-professional forrest-based carpenter, Anthony always gives a fascinating talk. This time he gives an intelligent and considered breakdown on the nebulous topic of cerebral protection.
Hypokalemia, Hypoxic Ischemic Encephalopathy, Nosocomial Pneumonia and Urinar...Jack Frost
Hypokalemia, Hypoxic Ischemic Encephalopathy, Nosocomial Pneumonia and Urinary Tract Infection.This presentation contains real names of persons involve of this particular study. This names should not be copied or rewritten. Used the data of this study as basis only. All rights reserved 2009.
Debate: Neurocritical Care Improves Outcomes in Severe TBISMACC Conference
Martin Smith and Mark Wilson debate whether neurocritical care improves outcomes in severe TBI.
Martin argues in favour of neurocritical care.
He concedes that longstanding and established practices are not as efficacious or innocuous as previously believed.
Very few specific interventions have been shown to improve outcomes in large randomised controlled trials. With the possible exception of avoidance of hypotension and hypoxaemia, most are based on analysis of physiology and pathophysiology.
Further, the substantial temporal and regional pathophysiological heterogeneity after TBI means that some interventions may be ineffective, unnecessary, or even harmful in certain patients at certain times.
Martin however, contends that improved understanding of pathophysiology and advances in neuromonitoring and imaging techniques have led to more effective and individualised treatment strategies. Ultimately, this has led to improved outcomes for patients.
In particular, the sole goal of identifying and treating intracranial hypertension has been superseded by a focus on the prevention of secondary brain insults. This is done by using a systematic, stepwise approach to maintenance of adequate cerebral perfusion and oxygenation.
Similarly, multimodal neuromonitoring also gives clinicians confidence to withhold potentially dangerous therapy. Particuarly in those with no evidence of brain ischemia/hypoxia or metabolic disturbance.
Mark Wilson on the other hand argues there is no benefit in neurocritical care following severe TBI.
The New England Journal of Medicine has published several articles that demonstrate no benefit from classic neurotrauma interventions (ICP monitoring, cooling, decompression). This is because factors such as ICP and CPP associate with bad outcomes by association rather than causation.
This debate will demonstrate that critical care just complicates things. Evidently, it is high time for the randomised trial between the very best neurocritical care and NOB therapy (Naso-pharyngeal, Oxygen and a Blanket).
Join Martin and Mark as they discuss the pros and cons of neurocritical care in the management of severe TBI.
For more like this, head to our podcast page. #CodaPodcast
Hypokalemia, Hypoxic Ischemic Encephalopathy, Nosocomial Pneumonia and Urinar...Jack Frost
Hypokalemia, Hypoxic Ischemic Encephalopathy, Nosocomial Pneumonia and Urinary Tract Infection. This presentation contains real names of persons involve of this particular study. This names should not be copied or rewritten. Used the data of this study as basis only. All rights reserved 2009.
Management of hypoxic ischemic encephalopathy (HIE) by Sunil Kumar Dahasunil kumar daha
Please find the power point on Management of hypoxic ischemic encephalopathy (HIE) . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
Research guru and PI for the ARISE study, college examiner and semi-professional forrest-based carpenter, Anthony always gives a fascinating talk. This time he gives an intelligent and considered breakdown on the nebulous topic of cerebral protection.
This slide show has been prepared to be presented in the 4th edition of World Congress on Endocrinology, Diabetes and Metabolism, (EDM 2023 Congress)
Sep 07-08, 2023,
Rome, Italy
I was honored to be invited by Prof. Nasser Ghaly Yousif on behalf of Al Muthanna University Organizing Committee to have a talk in Al Muthanna International Trauma Conference, May 9-11, 2020, Iraq, about updates in immunopathophysiology of COVID19. Prof. Yousif chaired the first day of the conference with high level of dignity and royalty. This slideshow was to be presented at the conference. My article may be found through:
https://doi.org/10.26434/chemrxiv.12271865.v1
This review article was presented in the 7th International joint cardiovascular congress held on Feb 28-29, 2019, in Convention Center, Shahid Rejaee Heart Hospital, Tehran, Iran
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
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
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
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.
Follow us on: Pinterest
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
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.
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.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
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.
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.
1. MOLECULAR PATHOBIOLOGY OF
BRAIN EDEMA IN NEUROLOGICAL
INJURY
ADVANCED CRITICAL CARE PHYSIOLOGY CLASSES, TUMS
Reza Nejat, M.D.
Anesthesiologist, FCCM
former-Assistant Professor, SBMU
2. Pathobiology of Brain Edema
Cerebral ischemia/reperfusion and
traumatic injuries result in:
sequences of metabolic impairment,
energy failure
mediator interactions such as glutamate
release and glutamate receptor
activation
Advanced Critical Care Physiology Classes
3. Pathobiology of Brain Edema
Mediator interactions such as glutamate
release and glutamate receptor activation:
excitotoxicity,
elevated intracellular calcium concentration,
mitochondrial dysfunction,
intracellular chaotically enzymatic interactions,
free radical production,
chaotic intrinsic nitric oxide production,
activation of apoptosis cascade,
inflammatory reactions.
Advanced Critical Care Physiology Classes
4. Pathobiology of Brain Edema
Cerebral edema:
a clinicopathological state
characterised by an increase in brain
water content (> 80%)
Advanced Critical Care Physiology Classes
5. Pathobiology of Brain Edema
Four Fluid Compartments:
Brain-blood (cerebral vessels),
Cerebrospinal fluid (CSF)
(ventricular system),
Interstitial fluid (brain parenchyma)
Intracellular fluid (neurons and glial
cells)
Advanced Critical Care Physiology Classes
6. Pathobiology of Brain Edema
Cerebral Edema:
Vasogenic
Cytotoxic/ionic/cellular
Interstitial/hydrocephalic
Osmotic/hypostatic
Hydrostatic
Advanced Critical Care Physiology Classes
7. Pathobiology of Brain Edema
Cerebral Edema:
Vasogenic: (the most common form)
primarily due to the breakdown of
BBB secondary to
mechanical disruption:
brain trauma, acute malignant hypertension,
radiation
chemical mediators:
tumours, inflammation and infection
Advanced Critical Care Physiology Classes
8. Pathobiology of Brain Edema
Cerebral Edema:
Cytotoxic/ionic/cellular:
BBB intact
Cellular Energy Failure
Disrupted Ionic Pumps
Anaerobic metabolism
GNT
Advanced Critical Care Physiology Classes
9. Pathobiology of Brain Edema
Cerebral Edema:
Interstitial/hydrocephalic:
Intraventricular pressure increases:
breakdown of ventricular ependymal
lining
transependymal migration of CSF into
extracellular space
Advanced Critical Care Physiology Classes
10. Pathobiology of Brain Edema
Cerebral Edema:
Osmotic/hypostatic:
Imbalance of osmolality between serum
plasma and brain parenchyma
Salt intoxication
Water intoxication
cellular and BBB integrity is maintained
SIADH, TBI with hypo-osmolal serum
Advanced Critical Care Physiology Classes
11. Pathobiology of Brain Edema
Cerebral Edema:
Hydrostatic:
Arterial pressure exceeds the upper limit
of autoregulation
There is venous congestion (head-down
position, pressure on the jugular veins,
high intrathoracic pressure).
Advanced Critical Care Physiology Classes
14. Pathobiology of Brain Edema
Cerebral Edema:
Vasogenic: (the most common form)
primarily due to the breakdown of
BBB secondary to
mechanical disruption:
brain trauma, acute malignant hypertension,
radiation
chemical mediators:
tumours, inflammation and infection
Advanced Critical Care Physiology Classes
15. Pathobiology of Brain Edema
BBB consists of endothelial cells, TJ,
basement membrane and foot processes
of astrocytes.
BBB to fulfill its function normally:
“neurovascular unit” should act in concert:
cerebral microvasculature endothelial cells,
neurons,
extracellular matrix,
astrocytes and pericytes
Advanced Critical Care Physiology Classes
18. Pathobiology of Brain Edema
Lipophilic molecules pass through BBB
easily
Ions and small molecules like glucose and
amino acids are transported through
specific channels and carriers
Large molecules such as peptides and
proteins are conducted via:
Endocytosis
transcytosis
hiring caveolae and clathrin-coated microvesicles
Advanced Critical Care Physiology Classes
19. Pathobiology of Brain Edema
Integrity of BBB:
Depends on the tight junctions (TJ)
located between the endothelial cells of
brain capillaries.
Advanced Critical Care Physiology Classes
20. Pathobiology of Brain Edema
Astrocytes and pericytes induce
endothelial cells to form the tight
junctions
Advanced Critical Care Physiology Classes
22. Pathobiology of Brain Edema
During BBB injury:
Initially, an increase in caveolae
Later, tight junction breakdown
Finally, endothelial cell injury
Caveolae:
plasmalemmal vesicles which allow protein
passage through fluid-phase transcytosis or
transendothelial channels
Advanced Critical Care Physiology Classes
26. Pathobiology of Brain Edema
BBB malfunction follows a biphasic
temporal course:
an early phase of high permeability
a more prolonged delayed phase of
leakiness.
Advanced Critical Care Physiology Classes
27. Pathobiology of Brain Edema
Disintegration of BBB:
inflammatory mediators,
reactive oxygen species (ROS),
VEGF,
matrix metalloproteinases (MMPs)
microRNAs
Advanced Critical Care Physiology Classes
29. Pathobiology of Brain Edema
BBB injury results in:
Activation of glial cells
Production of various mediators:
bradykinin, serotonin, histamine,
complement, arachidonic acid, NO and
leucotrienes
The movement of protein rich exudates
into extracellular space
White matter is more affected
Advanced Critical Care Physiology Classes
35. Pathobiology of Brain Edema
Astrocytes are highly branched cells:
Juxtaposed to the soma, dendrites and axons of neurons,
the plasma membrane of microglial cells,
oligodendrocytes, and other astrocytes,
can potentially influence and be influenced by a large
number of cells, synapses, and vascular structures
harbor virtually all of the constitutive metabolic enzymes,
especially glutamine synthetase and pyruvate carboxylase
Involved in the metabolism of glucose, ammonia, and
glutamate
Advanced Critical Care Physiology Classes
36. Pathobiology of Brain Edema
Astrocytes:
take up, metabolize neurotransmitters,
buffer changes in ECF ion concentration,
serve as intermediates in the cross talk
between neurons and blood vessels
Express iGluRs and mGluRs
Express 𝑲𝑲⁺𝑪𝑪𝑪𝑪⁺⁺ channels
Advanced Critical Care Physiology Classes
37. Pathobiology of Brain Edema
Astrocytes; pivotal role in:
Axonal Growth
Energy Metabolism
Neurotransmitter Homeostasis
Water/Electrolyte Balance
Immune Response
Advanced Critical Care Physiology Classes
38. Pathobiology of Brain Edema
Astrocytes are highly branched cells:
Rich in receptors of neurotransmitters, growth
factors, cytokines, and chemokines, transporters
for numerous molecules:
K⁺, water, glutamate, glutamine, glucose, ketone
bodies and lactate,
can change (transform) their phenotype and
proliferate in response to certain (usually
damaging) conditions.
Advanced Critical Care Physiology Classes
39. Pathobiology of Brain Edema
𝑮𝑮𝑮𝑮 𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮 + 𝑵𝑵𝑵𝑵𝟑𝟑 + 𝑨𝑨𝑨𝑨𝑨𝑨 = 𝑮𝑮𝑮𝑮 𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮𝑮 𝑮𝑮𝑮𝑮 + 𝑨𝑨𝑨𝑨𝑨𝑨 + 𝑷𝑷𝒊𝒊
rapid metabolism of IC glutamate is a
prerequisite for efficient glutamate clearance
from the extracellular space
Elevated concentrations of EC glutamate and
glutamate analogues in the brain can lead to
hyperexcitability, seizures and neuronal death
Advanced Critical Care Physiology Classes
42. Pathobiology of Brain Edema
During normal and
abnormal neuronal
activity, there is
cotransport of 3Na+,
1Cl−, 1H+ and
antiport 1K+ ion per
glutamate molecule
along with
water molecule.
Advanced Critical Care Physiology Classes
43. Pathobiology of Brain Edema
GNT
During ischaemia/hypoxia, energy dependent
pathways fail and glutamate accumulates to toxic
levels and abnormal surge of neuronal activity
happens through activation of :
N-methyl-D-aspartate (NMDA) R,
AMPA R,
mGlu R
Kinate R
Advanced Critical Care Physiology Classes
46. Pathobiology of Brain Edema
GNT
Na⁺ and Cl⁻ influx resulting in Ca⁺⁺ influx
Ca⁺⁺ influx & ROS generation (oxidative stress)
Ca⁺⁺ dependent conversion of XDH to XOD
Allowing H₂O₂ and O₂⁻• production
Ca⁺⁺ activated PLA₂ and NOS
NMDA receptor-mediated K⁺ efflux resulting in
neuronal apoptosis
Advanced Critical Care Physiology Classes
47. Pathobiology of Brain Edema
GNT
ROS production due to NMDA activation
Uncoupling of MTC
Leakage of electron from respiratory chain in
MTC
Arachidonic acid metabolism by oxidases
Inactivation of PFK, LDH, CPKinas
Depletion of anti-oxidant capacity of the cell
Advanced Critical Care Physiology Classes
49. Pathobiology of Brain Edema
The time course of ROS production
in GNT:
Early phase (up to 30 min)
Later phase (3-24 h)
Advanced Critical Care Physiology Classes
50. Pathobiology of Brain Edema
Early Phase:
Glutamate binding to receptor;
Calcium influx in cytosol;
XDH→XOD conversion;
ROS production;
ROS-induced cyt c release;
Cyt c as ROS scavenger;
Cyt c as electron donor;
Cyt c-dependent energy generation.
Advanced Critical Care Physiology Classes
51. Pathobiology of Brain Edema
Late Phase:
Glucose uptake increase;
Increase in lactate production via
glycolysis;
Mitochondrial shuttle impairment;
NADH oxidation via mitochondrial
NADH-b5-oxidoreductase;
Massive ROS production by mitochondria;
Mitochondrial permeability transition.
Advanced Critical Care Physiology Classes
53. Pathobiology of Brain Edema
Hypoxia/Ischemia:
Increases transcription of hypoxia-inducible
factor 1 (HIF-1) gene.
HIF-1, activates hypoxia-responsive element
(HRE) in the genome,
HRE, a transcription factor regulates the
transcription of:
multiple genes encoding EPO, vascular
endothelial growth factor (VEGF) and platelet
derived growth factor,
over 100 other HIF responsive genes including
those involved in cell metabolism encouraging
anaerobic production of ATP, in addition to cell,
survival, proliferation and migration and
vasodilation.
Advanced Critical Care Physiology Classes
54. Pathobiology of Brain Edema
HIF-1α dependent signaling pathways
might also be a source of
neuroinflammation/apoptosis and
hence BBB dysfunction.
HIF-1α in hypoxic brain insult
increases expression of VEGF,
VEGFR, MMP-9 and AQP-4
Astrocytes and pericytes produce
VEGF and MMPs
Advanced Critical Care Physiology Classes
55. Pathobiology of Brain Edema
MMPs:
belong to a 25-member family of zinc-
dependent endopeptidases
secreted in an inactive form in
untraceable or in a very delicately
controlled low concentration in the
adult healthy brain.
contribute to degrading the extra-
cellular matrix (ECM).
Advanced Critical Care Physiology Classes
57. Pathobiology of Brain Edema
MMPs:
several significant physiological
potentials involved in:
growth,
development,
tissue repair and wound healing
synaptic plasticity
neurite growth
myelinogenesis.
Advanced Critical Care Physiology Classes
58. Pathobiology of Brain Edema
MMPs:
up-regulated and activated in ischemic
and other brain injuries,
Its latent form is activated by:
Endogenous and exogenous plasminogen
activator
Furin
free radicals
Advanced Critical Care Physiology Classes
59. Pathobiology of Brain Edema
AQP-4
integral membrane proteins
which play important roles in
mediating water homeostasis and
bidirectional passive trans-
cellular water transfer in
response to osmotic gradient.
the expression of this channel is
modulated by HIF-1 and VEGF
Advanced Critical Care Physiology Classes
60. Pathobiology of Brain Edema
AQPs in the CNS contribute to:
Glymphatic (Glial Lymphatic) pathway:
couples cerebrospinal fluid (CSF) influx
to interstitial spinal fluid (ISF) efflux
through convective bulk flow from peri-
arterial to peri-venous spaces (Virchow-
Robin spaces) in microvasculature of the
brain
Advanced Critical Care Physiology Classes
61. Pathobiology of Brain Edema
AQPs are involved in:
potassium buffering,
waste material clearance,
neuroinflammation,
osmosensation,
astroglial cell migration,
Ca signaling,
neural signal transduction,
long-term plasticity,
spatial memory,
cell adhesion,
regulating cerebral edema
Advanced Critical Care Physiology Classes
65. Pathobiology of Brain Edema
AQP-4
expression has
an impact on
BBB integrity
*Cytotoxic
edema-induced
vasogenic
edema
Advanced Critical Care Physiology Classes
66. Pathobiology of Brain Edema
Vascular endothelial cell growth
factors (VEGF), a family of cytokines,
induce angiogenesis through
proliferation, sprouting, migration of
the endothelial cells and new tube
formation by these cells.
Found in pericytes in the border of
brain lesions
After binding withVEGFR-2 increases
vascular permeability through
activating cGMP and a NO-dependent
pathway
Advanced Critical Care Physiology Classes
68. Pathobiology of Brain Edema
VEGFs may be inactivated:
when they bind with heparan sulfate
proteoglycan (HSPG) moieties of the
ECM or
are trapped by a secreted isoform of
VEGF receptors (sVEGF-R)
MMPs may split the bound form of
VEGF
VEGF may be destructed by proteases
(like MMPs)
Advanced Critical Care Physiology Classes