by post graduates from Maratha Mandal's NathajiRao Halgekar Institute of Dental Sciences, Belgavi.
A step wise presentation of Amylodosis covering,
INTRODUCTION
DEFINITION
HISTORY
PHYSICAL NATURE
CHEMICAL NATURE
CLASSIFICATION
PATHOGENESIS
STAINING CHARACTERISTICS
DIAGNOSTIC TESTS
MORPHOLOGY
CLINICAL FEATURES
TREATMENT
PROGNOSIS
by post graduates from Maratha Mandal's NathajiRao Halgekar Institute of Dental Sciences, Belgavi.
A step wise presentation of Amylodosis covering,
INTRODUCTION
DEFINITION
HISTORY
PHYSICAL NATURE
CHEMICAL NATURE
CLASSIFICATION
PATHOGENESIS
STAINING CHARACTERISTICS
DIAGNOSTIC TESTS
MORPHOLOGY
CLINICAL FEATURES
TREATMENT
PROGNOSIS
Amyloidosis is a condition associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damange and functional compromise. (Robbins Basic Pathology, 9th Edition)
The following slideshow deals with the classification of Amyloidosis:
A Powerpoint presentation on the epidemiology, etiology, pathogenesis, clinical features, diagnostic work up and treatment of the common types of amyloid.
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Amyloidosis is a condition associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damange and functional compromise. (Robbins Basic Pathology, 9th Edition)
The following slideshow deals with the classification of Amyloidosis:
A Powerpoint presentation on the epidemiology, etiology, pathogenesis, clinical features, diagnostic work up and treatment of the common types of amyloid.
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- 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
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.
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
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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.
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.
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.
2. OUTLINES
Definition
Physical Nature of Amyloid
Chemical Nature of Amyloid
Classification
Pathogenesis
Clinical Correlations
Stainings
Morphology In Organs
3. Disease characterized by deposition of amyloid in the tissue.
Amyloid = starch like
Amylum – Starch (Latin) + Oid (resembling)
Definition
4. Amyloid, a pathologic proteinaceous substance, deposited between cells
in various tissues and organs of the body in a wide variety of clinical
settings (inherited and inflammatory disorders).
Amyloid refers to an extracellular abnormal deposit of insoluble
polymeric protein fibrils in tissues and responsible for tissue
damage and functional compromise.
These abnormal fibrils are produced by the aggregation of misfolded
proteins (which are soluble in their normal folded configuration).
Definition
5. Amyloidosis is not a single disease; rather it is a group of
diseases having in common the deposition of similar-appearing
proteins.
Amyloid refers to a group of diverse extracellular protein deposits
that have
(1) common morphologic properties.
(2) affinities for specific dyes.
(3) when stained, a characteristic appearance under polarized light.
Definition
6. These fibrils are continous,
nonbranching, insoluble,
linear, rigid and measures 7.5 - 10
µm in diameter .
Physical Nature of Amyloid
7. Physical Nature of Amyloid
By electron microscopy, amyloid is seen to be made up largely of
nonbranching fibrils of indefinite length.
This structure is identical in all types of amyloidosis.
The fibers have characteristic cross-β-pleated sheets and are
responsible for the distinctive staining and birefringence of Congo
red-stained amyloid.
8.
9. Chemical Nature of Amyloid
A fibrillary protein (95%) which is characteristic for each
different type of disease.
Amyloid P component (5%) consists of stacks of doughnut-
shaped proteins. All different types of amyloid possess this
protein.
A glycosoamynoglycan. This is the part of the molecule
responsible for the positive reaction with iodine.
10. The most common forms of amyloid fibril proteins are:
1. Amyloid light chain(AL)-made up of complete immunoglobulin
light chain, derived from the lambda light chain.
2. Amyloid associated(AA)-derived from a unique non-Ig protein
made by the liver, derived from larger precursor protein
SAA(serum amyloid associated protein)
Chemical Nature of Amyloid
11. others
3. Aβ2 Microglobulin(AβM)-seen in patients on long term
hemodialysis
4. Transthyretin(TTR) - serum protein synthesized in liver &
transports thyroxine and retinol.
5. Amyloid β-peptide(Aβ)- seen in Alzheimers disease.
6. Prion proteins(APrP)
7. Precursor of AA=SAA(Serum Amyloid Associated Protein)
Chemical Nature of Amyloid
16. • Variable presentation: no clinical manifestations, or it may cause
death.
• At first nonspecific symptoms such as weakness, weight loss,
light-headedness, or syncope.
• Specific findings appear later and most often relate to renal,
cardiac, and gastrointestinal involvement.
• The symptoms depend on the magnitude of the deposits and on
the organs affected.
Clinical Correlations
18. Clinical Correlations
Liver Hepatomegaly, Alkaline phosphatase
elevation, Hepatic rupture
Endocrine organs Hypothyroidismdue to infiltration,
development of Diabetes Mellitus
Neurology Peripheral neuropathy, autonomic
dysfunction, Dementia (Alzheimers
disease), Hemorrhagic strokes
Soft tissue/ENT Carpal tunnel syndrome, voice
changes, nail changes
19. Stainings
1. Stain on Gross- oldest method
used by Virchow on cut section of
gross specimen is Lugols Iodine
which imparts mahogany brown
colour to the amyloid deposit which
on addition of sulfuric acid turns
blue.
20. 2. In routine histological sections
(hematoxylin and eosin stains)amyloid
appears amorphous, eosinophilic, hyaline,
extracellular substance.
* However all proteins are stained pink
by eosin and thus this stain is not specific.
Stainings
21. 3. All amyloids stain pink-red with
the Congo Red stain.
Stainings
22. But when these sections are viewed with
polarized light they exhibit a apple green
birefrigence. This feature of amyloid can
be used to identify it in tissue sections.
Stainings
23. OTHER SPECIAL STAINS
Methyl & Cresyl Violet - Metachromatic stains, pink color
ThioFlavin T & S - Exhibits Flouroscence
Alcian Blue - Stains blue, due to presence of glycosaminoglycans
Periodic Acid Schiff (PAS) - Stains Pink
Immunohistochemistry - To distinguish AL, AA & ATTR types
24. Morphology In Organs
Primary amyloidosis cannot reliably be distinguished from the
secondary amyloidosis but more often it involves the heart,
kidney, gastrointestinal tract, skin and tongue.
Secondary amyloidosis usually involves kidneys, liver, spleen
and lymph nodes as well as many other tissues.
Macroscopically the affected organs are often enlarged and
firm and have a waxy appearance.
25. Morphology in Kidney
Most common organ involved.
Grossly, the organ is swollen, mottled, pale and yellow to
orange in colour
Histologically the amyloid is deposited in the
1) Glomeruli, with progression there is hyalinization of the
glomeruli.
2) Peritubular region extending into interstitium.
3) Blood vessels: hyaline thickening of the arteriolar wall and
narrowing of lumen, eventually causing ischemia with tubular
atrophy and interstitial fibrosis.
26.
27.
28. Morphology in Spleen
May cause splenomegaly.
The organ is waxy in consistency and the cut surface is
grayish.
Splenic corpuscles become large, gray and translucent.
There are two patterns of deposition.
1) Sago spleen.
2) Lardaceous spleen.
29.
30.
31.
32. Morphology in Liver
May cause hepatomegaly.
Grossly, Liver is enlarged with rounded edges, doughy in
consistency, pits on pressure and ruptures easily because of its
friable nature.
The amyloid appears first in the space of Disse and then
progressively encroaches on adjacent hepatic parenchymal cells
and sinusoids.
In time due to pressure atrophy disappearance of hepatocytes
replacement of large areas of liver by amyloid.
Vascular involvement & deposits in Kupffer cells are frequent.
33.
34.
35.
36. Morphology in Heart
Grossly, heart is enlarged and firm.
• Epi/endocardium and valves show tiny nodular deposits.
Microscopically-focal subendocardial accumulations;
in primary form, deposits are seen around myocardial fibres in ring
forms also known as ring fibres.
In localized, deposits seen in left atrium.
37.
38.
39. REFERENCES
Immunopathology including Amyloidosis . In: Mohan H ed. Text book of
pathology. 6th ed. Jaypee publication: India, 2010:82-92
Amyloid. In Vowles G H, Bancroft J D eds. Theory and Practice of Histological
Techniques. 6th ed. Churchill Livingstone Elsevier; 2002: 261-281
Robbinson's basic pathology 8 ed
Harsh Mohan -Textbook of Pathology 6th Ed.
Color atlas of pathology
https://www.sciencedirect.com/science/article/pii/S105488071500085X#s0030
http://ilovepathology.com/amyloidosis-part-2-pathogenesis-classification/
www.unckidneycenter.org
http://webpathology.com
Amyloid is a starch-like substance which stains brown/blue/black with Iodine
Amyloidosis refer to variety of condition where in normally soluble proteins become insoluble and are deposited in the extracellular space of various organs or tissues, disrupting their normal function.
Birefringence = double refraction of light
Amyloid is specially stained with Congo Red. Under polarized light, red-green dichroism (birefringence) is noticed because of alignment of fibrils. β-pleated sheet configuration is seen in X-ray diffraction.
The amyloid forms a β-pleated sheet despite their chemical heterogeneity.
β-pleated sheet are extremely hydrophobic do not dissolve in proteolysis
This makes the fibril resistant to digestion by macrophages and phagocytic cells and hence accumulates in tissues (aggregation).
Amyloid is specially stained with Congo Red. Under polarized light, red-green dichroism (birefringence) is noticed because of alignment of fibrils.
Meanwhile β-pleated sheet configuration is seen in X-ray diffraction.
AP & GAG are non fibrillary proteins
Another non fibrillar amyloid protein is Apolipoprotein-E (apoE), alpha-1-anti chymotrypsin, Protein X
P component = a type of glycoprotein, a 25kDa molecular weight, inhibits the differentiation of monocyte-derived fibroblast-like cells called fibrocytes, promotes the formation of immuno-regulatory macrophages, and inhibits neutrophil adhesion to extracellular matrix proteins.
The P-component which is a glycosa-amino-glycan (GAG) facilitates polymerization of amyloid.
The GAG makes the amyloid to stain with iodine. The amyloid is resistant to enzymatic digestion and progressively accumulate in tissues until the underlying disease process persists.
Amyloid light chain(AL), Amyloid associated(AA), Aβ2 Microglobulin(AβM), Transthyretin(TTR) - serum protein synthesized in liver & transports thyroxine and retinol, Amyloid β-peptide(Aβ), Prion proteins(APrP), Precursor of AA=SAA(Serum Amyloid Associated Protein), AApoAl (Apolipoprotein A1), AGel (Gelsolin), ALys (Lysozyme), Afib (Fibrinogen alpha chain), Acys (Cystasin C)
Plasma cell dyscrasias = plasma cell proliferative disease, including Multiple Myeloma, Waldenstrom’s macroglobulinemia
Familial Mediterranean fever - Autosomal recessive, Autoinflammatory syndrome, Excessive production of IL1 in response to inflammation, Characterized by attacks of fever with serosal inflammation, Wide spread amyloidosis, AA protein
Amyloidosis results from abnormal folding of proteins, which are deposited as fibrils in extracellular tissues and disrupt normal function.
Under normal circumstances, these abnormal or misfolded proteins are degraded by proteasome pathway intracellularly and by the macrophages extracellularly.
In Amyloidosis, these control mechanisms fail or there may be mutations which favor misfolding which further leads to accumulation and aggregation to form fibrils.
Non-fibrillary proteins (Amyloid P component (5%) & A glycosoamynoglycan) facilitate aggregation and protection against solubilisation.
So all these factors result in deposition of misfolded protein outside the cells.
Renal involvement: proteinuria, can cause of the nephrotic syndrome. Progressive obliteration of glomeruli in advanced cases leads to renal failure and uremia
The enlargement and ischaemic anoxia leads to tubular epithelial degeneration and necrosis, marked proteinuria, nephrotic syndrome, uremia and death
Macroglossia – enlargement of tongue drooling, speech impairment, difficulty eating, stridor, snoring, airway obstruction
GI: Dysphagia, malabsorption, GI bleeding, constipation, nausea
Cardiac: Heart failure, arrhythmias, hypotension, constrictive pericarditis & amyloid deposits in valves.
Cardiac amyloidosis: insidious congestive heart failure. The most serious complications are conduction disturbances and arrhythmias, which may prove fatal.
Hypovolumic or haemorrhagic shock may occur following hepatic rupture.
Hepatocellular atrophy occurs from pressure and nutritional deficiency alkaline phosphatase elevation
DM : In pancreatic amyloidosis, leads to islet cell destruction and development of Diabetes mellitus.
Neurologic: Peripheral neuropathy, autonomic dysfunction
Soft tissue/ENT: carpal tunnel syndrome, voice changes, nail changes
History
• First described by Rokitansky in 1842.
• Term first used by Rudolf Virchow in 1854 based on the color after staining it with crude iodine staining techniques.
• Later recognized as Protein by Friedreich and Kekule 5 years later.
Light microscope: amyloid appears as amorphous, eosinophilic, hyaline, extracellular substance that gradually encroaches on and produces pressure atrophy of adjacent cells.
On congo red stain: amyloid gives a pink or red color under ordinary light and an apple green birefringence under polarizing light.
Grossly, the organ is swollen, mottled, pale and yellow to orange in colour
Deposit is in the splenic follicles, producing tapioca-like granules on gross inspection, called sago spleen.
Deposit in splenic sinuses and connective tissue of the red pulp. Fusion of deposits gives rise to large, areas of amyloidosis, designated the lardaceous spleen.
Lard = pig fat
A, The pink acellular amyloid material is seen in the red pulp causing atrophy of while pulp.
B, Congo red staining shows Congo philia as seen by red-pink colour.
C, When viewed under polarising microscopy the corresponding area shows apple-green birefringence.
Space of Disse (space between the hepatocytes & sinusoidal endothelial cells)
May cause hepatomegaly.
Grossly, Liver is enlarged with rounded edges, doughy in consistency, pits on pressure and ruptures easily because of its friable nature.
Histologically the deposits are subendocardial and within the myocardium between the muscle fibers.
Expansion of these myocardial deposits eventually causes pressure atrophy of myocardial fibers.
When they are subendocardial, the conduction system may be damaged, causing electrocardiographic abnormalities.
Fig. 4. Gross pathologic features of cardiac amyloidosis. (A) Pale myocardial mottling (arrowhead) can sometimes be seen in the setting of extensive amyloid deposition; (B) Amyloid can preferentially deposit in the ventricular septum, leading to disproportionate septal thickening and an increased ventricular septal-to-free wall ratio; (C–D) Endocardial deposition of amyloid can produce a mottled appearance or a roughened texture to the endocardial surface (C), which can sometimes also involve the atrioventricular valves (D).