1. The document discusses muscle biopsy indications, processing, and morphology as it relates to myopathies. It covers normal muscle histology and fiber typing as well as various staining techniques used.
2. Specific myopathies discussed include congenital myopathies like central core disease, multicore disease, and nemaline myopathy. Acquired myopathies like inflammatory myopathies and muscular dystrophies are also summarized.
3. The approach to interpreting a muscle biopsy involves correlating clinical information with histological findings on H&E and specialized stains to identify features characteristic of different myopathies.
MYOPATHIES A SPECIAL AND SEPERATE ENTITY WITH SPECIFIC FEATURES IN EACH DISORDER MAKING US EASY FOR DIAGNOSIS,CONFIRMATION BY MUSCLE BIOPSY.THE SEMINAR WAS PRSENTED ON 06/07/2011...AT 09.00AM
HAVE A LOOK ..AND COMMENT..WITHOUT BIAS..
brief description and summary of Acute disseminated Encephalomyelitis-most common Paediatric demyelinating disorder-clinical features, epidemiology. Approach between MS and ADEM
Myopathies - In detail (Classification and images) Dr. Tushar Kariya
In this presentation I've tried to cover myopathies, its classification and related images with H&E and special stain wherever its possible. Hope it helps you guys to understand the entity better.
muscle biopsy site indications staining processing of muscle biopsy.pptxDrDivitasaxena1
Muscle biopsy is indicated for general conditions and specific conditions
General ones include weakness of uncertain cause-generalized, proximal, floppy infant syndrome , in case of persistently increased muscle enzymes or in case of muscle pain cramps and stiffness
Specific reasons include hereditary muscle disease connective tissue diseases metabolic diseases drug induced myopathy
MYOPATHIES A SPECIAL AND SEPERATE ENTITY WITH SPECIFIC FEATURES IN EACH DISORDER MAKING US EASY FOR DIAGNOSIS,CONFIRMATION BY MUSCLE BIOPSY.THE SEMINAR WAS PRSENTED ON 06/07/2011...AT 09.00AM
HAVE A LOOK ..AND COMMENT..WITHOUT BIAS..
brief description and summary of Acute disseminated Encephalomyelitis-most common Paediatric demyelinating disorder-clinical features, epidemiology. Approach between MS and ADEM
Myopathies - In detail (Classification and images) Dr. Tushar Kariya
In this presentation I've tried to cover myopathies, its classification and related images with H&E and special stain wherever its possible. Hope it helps you guys to understand the entity better.
muscle biopsy site indications staining processing of muscle biopsy.pptxDrDivitasaxena1
Muscle biopsy is indicated for general conditions and specific conditions
General ones include weakness of uncertain cause-generalized, proximal, floppy infant syndrome , in case of persistently increased muscle enzymes or in case of muscle pain cramps and stiffness
Specific reasons include hereditary muscle disease connective tissue diseases metabolic diseases drug induced myopathy
The term necrosis is derived from a greek word nekros which means dead body.
Definition: Necrosis is defined as local or focal death of cells along with degradation of tissues by hydrolytic enzymes released from lysosome of the cell.
It is often associated with surrounding inflammatory reaction.
Necrosis is a series of morphological changes that follows cell death due to the irreversible cell injury/lethal cell injury/pathological cell injury.
Cellular Adaptation
as cells encounter stresses they undergo functional or structural adaptations to maintain viability / homeostasis.
Injury - altered homeostasis
if limits of the adaptive response are exceeded or if adaptation not possible, a sequence of events called cell injury occurs.
Reversible Cell Injury
removal of stress results in complete restoration of structural & functional integrity.
b) Irreversible Cell Injury / Cell Death
if stimulus persists or is severe enough from the start, the cell suffers irreversible cell injury and death.
2 main morphologic patterns: necrosis & apoptosis.
Adaptations are reversible changes in the size, number, phenotype, metabolic activity, or functions of cells in response to changes in their environment.
Physiologic adaptations are responses of cells to normal stimulation by hormones or endogenous chemical mediators
Pathologic adaptations are responses to stress that allow cells to modulate their structure and function and thus escape injury.
Hypertrophy refers to an increase in the size of cells, that results in an increase in the size of the affected organ
The hypertrophied organ has no new cells, just larger cells.
Types:
a) physiologic b) pathologic
Causes:
a) increased functional demand b) hormonal stimulation
this is a series of notes on general pathology, useful for undergraduate and post graduate pathology students. Notes have been prepared from standard textbooks and are in a format easy to reproduce in exams.
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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!
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.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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
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
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
4. HISTOLOGICALLY:
Skeletal muscle is
composed of elongated,
multinucleate ,unbranched
contractile cell described as
mucle fibre.
Characteristic cross-
striations seen on LM d/t
arrangement of contractile
protein
5. TYPES OF MUSCLE FIBRES:-
In normal muscle there are three types of fibers: darkest
muscle fibers (type 1), intermediate (type 2 b) and lightest
muscle fibers (type 2 a).
No or little variation in size.
No or little interstitial tissue.
Type 2 C fibers are the precursors of all other fiber types. Up
to 20 weeks of gestational age all muscle fibers are 2 C
(muscle cell precursors). Type 1 fibers begin to appear after
20 weeks gestation and type 2 (A and B) begin to appear
after 30 weeks of gestation.
At birth (40 weeks gestation) there are about 15 to 20 % of
type 2 C. At 1 year of age the composition muscle is: type 1
(60 to 65%); type 2 (A and B) (30 to 35%); and 2 C (3 to 5%).
(Victor Dubowitz. Muscle biopsy: a practical approach. Second edition. London: Bailliere
Tindall; 1985).
10. ATPASE STAIN AT PH 9.4
ATPase at ph 9.4 shows a normal
‘checkerboard’ or ‘mosaic’ distribution of
fibre types 1 and 2. Type 2 fibres stain
darkly.
Normal muscle. In the alkaline adenosine
triphosphatase (ATPase) reaction, type 1
fibers are light, and type 2 fibers are dark
(ATPase, pH 9.4, counterstained with
eosin).
11. ATPASE STAIN AT PH 9.4/4.6/4.3
‘Normal skeletal muscle stained for myosin ATPase at preincubation pH 9.4 (a), pH
4.6(b) and pH 4.3 (c). The different fibre types, I, IIA, IIB and IIC stain dark,
intermediate or pale,depending on the preincubation pH and consequently the
degree of inhibition of the activities of their different ATPases.
12. PHOSPHORYLASE STAIN:
Frozen section stained for phosphorylase. Type 2 fibres are stained darkly
but this reaction is not used routinely to demonstrate fibre type differentiation.
Complete absence of staining is typical of McArdle’s disease (Type V
Glycogen Storage Disorder.).
13. SDH STAIN:-
Stain for succinic dehydrogenase is
paler and has a particulate
appearance due to selective staining
of mitochondria.
14. COX STAIN:-
Staining for cytochrome oxidase (COX) shows a similar distribution to SDH staining
(more prominent in Type 1 fibres) but in this stain the end product is golden brown.
15. NADH-TETRAZOLIUM REDUCTASE:
NADH-TR stained frozen section shows positive staining of both the sarcoplasmic
reticulum and mitochondria, the latter more numerous in type 1 fibres.
16. OTHER STAINS:
Verhoeff Van-Gieson (VVG) stain of
frozen tissue to show fibrous tissue
and elastin .The fine black dots
represent mitochondria and the
intermyofibrillary network.
A modified PAS stain to
demonstrate glycogen. Type 2
fibres which are dependent on
intrinsic glycogen stain darkly.
17. SPECIAL STAINS CONT…
Oil Red-O in frozen section
demonstrates normal distribution of
fine lipid droplets within muscle
fibres, more prominent in type 1
fibres.
The modified Gomori trichrome stain
identifies mitochondria as small red
dots within the muscle fibre, most
numerous in type 1 fibres and at the fibre
periphery, in the subsarcolemmal zone
27. TRANSPORTATION OF BIOPSY:
Muscle may be saved in saline moistened guage for several hrs.
Keep the specimen cool.
Do NOT immerse in saline ,fixative or other liquid.
Frozen muscle may be safely shipped "overnight” with adequate dry ice.
PRESERVATION OF BIOPSY:
• Freeze most tissue in isopentane precooled to -160oC in liquid nitrogen.
• Frozen muscle for histochemistry provides
• Excellent muscle fiber morphology
• Most diagnostic information with light microscopy
• Freezing process should be rapid to prevent artifact.
• Store frozen muscle at -80oC.
• Fix some muscle in 3% glutaraldehyde.
• Embed most fixed muscle in plastic
• For ultrastructural analysis, if necessary
• Good visualization of muscle endomysial capillaries
• Fix some muscle with 10% formalin
Paraffin embedded material
• Useful for surveys for inflammation & morphology of inflammatory
cells
• Gives poor muscle fibre morphology
28. STAINS:
1.H&E- general architecture & morphology.
2.Masson`s trichome- Collagen, fibrosis.
3.Mod Gomori`s Trichome- fibrosis, inflammation, rods or inclusion,ragged red
fibers.
4.PAS- glycogen storage disorder, denervated fibers.
5.Oil red O- lipid storage disorder.
6.Acid phosphatase- lysosomal enzymes ,necrotic fibres.
7.Crystal voilet, Congo Red-amyloid.
8.ATPase PH 9.4 - Type 1 fibres pale
Type 2 fibres dark
9. ATPase PH 4.6 - Type 1 fibres dark
Type 2 fibres pale
10. NADH –TR - Sarcoplasmic structural details,Cores, target/targetoid fibres,
lobulated fibres.
11.SDH- oxidative enzyme activity(mitochondria)
12.Cytochrome C Oxidase- mitochondrial enzyme activity
13.NSE-lysosomal ¯ophage activity
29. GENERAL REACTIONS TO MUSCLE
INJURY:-
• Dysvoluminal Change:-
One of the fundamental change in muscle biopsy is variation in muscle fibre size.
Atrophy: d/t decreased trophic stimulation, malnutrition, aging or ischemia.
Hypertrophy: Absolute or Compensatory.
Morphometric Analysis:- can be done Directly by Eyepiece Micrometer or
Electronically by computerised apparatus. Smallest diameter or circumference of
200 fibres must be recorded.
Selective or Non-Selective.
Type 1: Congenital Myopathies, Myotonic Dystrophies.
Type 2: Corticosteroid Myopathy, MG, Acute Denervation, Disuse, Malignancy.
Non-selective: Chronic Denervation.
Type 1 Hypertrophy: Endurance training, Werdnig-Hoffman disease.
Type 2 Hypertrophy: Sprinters, Congenital fibre type Dysproportion.
Non-selective Hypertrophy: Acromegaly, limb-girdle Dystophy, Myotonia
Congenita.
31. ATPASE PH 9.4 :-
Type 2 fibre atrophy in a patient with prolonged
immobilization (Disuse Atrophy).
32. • Reaction of the Sarcolemmal Nuclei:-
Normally nuclei are subsarcolemmal in 95% of muscle fibres.
>10% of fibres showing nuclear internalization, without
sarcoplasmic compromise strong suspicion of myotonic
dystrophy.
34. • Fibre Necrosis:-
• Minor part of the pathology in
many muscle disease.
• Widespread in Muscular
Dystrophies and in
Inflammatory Myopathies.
• Bright eosinophilic Pale pink
• Cytoplasm : Granular
Vacuolated Fragmented
• Nucleus: Internalised,
Pycnotic/Karyorrhectic.
36. • Fibre Regeneration:-
• Fibre Necrosis Stimulus for Fibre
Regeneration.
• Histologically:
• Sarcoplasmic Basophilia.
• Internalised nuclei, increased in
number
• large with dispersed chromatin and
prominent nucleoli.
• Ultrastucturally: large amount of
ribosomes.
H&E
37. • Interstitial Reaction:- Inflammatory infiltrates in polymyositis,
systemic comnnective tissue diseases/vaculitis. In most of
chronic myopathies muscle is replaced by fibrous and fatty
tissue.
H&E
38. MYOPATHIES:-
The myopathies are neuromuscular or musculoskeletal disorders in which
the primary symptom is muscle weakness due to dysfunction of muscle
fibre.
Hence Muscular diseases can be classified as neuromuscular
or musculoskeletal in nature. Some conditions, such as myositis, can be
considered both neuromuscular and musculoskeletal.
40. APPROACH TO A CASE :-
History:
Four major pieces of clinical information are critical for the pathologist:
Is the condition a long standing or newly onset condition?
Is the condition progressive or relatively static?
Are there any associated systemic conditions such as heart problem or
autoimmune disease?
What is the serum CPK level?
Other helpful clinical information:
History of myoglobinemia.
Family history of neuromuscular disease.
Sex and age.
Results of EMG studies.
Muscle groups being affected.
Presence of contracture.
Site of biopsy.
Therapy and medication at the time of biopsy.
41. LAB WORKUP:-
Creatine kinase level: To rule out certain categories of
myopathies because different myopathies tend to generate a
different levels of elevation in CPK.
•High: (e.g. Dystrophinopathies) 200-300 times of normal.
•Intermediate: (e.g. Inflammatory myopathy) 20-30 times of
normal.
•Low: (e.g. Neurogenic disorder) 2-5 times of normal.
44. CENTRAL CORE DISEASE:-
Central clear zone ("core") in muscle fibers
NADH-TR stain: Well defined central region of
reduced staining
Cores run whole length of muscle fibres.
48. CENTRONUCLEAR / MYOTUBULAR
MYOPATHY:-
Central nuclei: Especially in smaller fibers
Clefts / Basophilis: In center of other muscle fibers
Rings (Necklaces): In some muscle fibers
Gomori trichrome stain
H&E stain
50. NEMALINE (ROD) MYOPATHY:-
Light microscopy
• Rods best visualized with
Gomori trichrome stain
• Dark blue structures
• Most in muscle fiber
cytoplasm
Contain
• Z-line like material
• α-actinin, actin & tropomyosin
± desmin at the periphery
Located in sarcoplasm: Often in
regions with disrupted
sarcomere structure.
*Gomori trichrome showing
Nemaline rods in gastrocnemius muscle from 4
month old child.
51. NEMALINE (ROD) MYOPATHY:-
H& E stain
Variable muscle fibre size
Refractile rods can be seen
Focal (bright green), large and small aggregates
of actin are present in some muscle fibers
Phalloidin staining for actin
54. MUSCULAR DYSTROPHIES:-
Duchenne Muscular Dystrophy:
• Most common dystrophy
• Most severe
• X-linked recessive- affects boys
• Neurologically intact at birth
• First sign when child attempts to walk/stand
• Weakness begins in pelvic girdle muscle then extent to shoulder
girdle sparing face muscle and swallowing
• Psedohypertrophy of calves and buttock- fatty infiltration and
reactive
55. DMD:-
• Elevated serum creatine kinase- first decade of life
• Early death d/t cardiomyopathy
• Multiple exonic deletion DMD gene on chr Xp21 encoding
dystrophin
• Bx- fiber necrosis and regeneration
• - hyaline fibers
• Immunostain for membrane associated dystrophin-
absence of immunostaining diagnostic of disease
56. DMD:-
Muscle fiber size: Varied; Small fibers are rounded or polygonal; Occasional hypertrophic fiber
Myopathic groups of small necrotic (Black arrow) & regenerating (White arrow) muscle fibers
Internal nuclei: Occasional
Endomysial connective tissue: Normal to mildly increased
Perimysium: Early replacement by fat
57. DMD LATE (10YRS)
Endomysial connective tissue: Increased
Fiber size: Variable
Small fibers: Rounded
Large or hypercontracted muscle fibers: Scattered
Necrotic fibers (Arrow): Scattered
58. DMD (DYDTROPHIN 1 STAIN)
Duchenne MD: Dystrophin absent from surface of muscle fibers
Normal: Dystrophin present near surface of muscle
fibers
59. WESTERN BLOT OF DYSTROPHIN
FROM DYSTROPHINOPATHIES
Lane 1: Becker dystrophy; Dystrophin has reduced abundance but normal size.
Lane 2: Becker dystrophy; Dystrophin has reduced size and abundance.
Lane 3: Normal; Dystrophin has normal size and amount.
Lane 4: Duchenne dystrophy; Almost no protein is present.
Lane 5: Duchenne outlier; Dystrophin has severely reduced abundance.
60. BECKER MUSCULAR DYSTROPHY:-
• Late onset, less severe clinically , slower in progression.
• X-linked disorder with exon deletions leading to abnormal but partially
functional dystrophin.
Clusters of neighbouring necrotic or regenerating muscle fibers all at same
stage- Most distinctive myopathic change in Becker's muscular dystrophy.
Stages
• Necrosis of Muscle Fibers
• Phagocytosis
• Several neighboring necrotic muscle fibers replaced by cells
• Phagocytic cells: Esterase-positive;
• Regenerating muscle fibers: Muscle fiber properties
• Small; Rounded; Basophilic
• Positive stains for: ATPase, NADH; Esterase
• Regenerated muscle fibers: Immature
• Cluster of intermediate-sized, basophilic muscle fibers
• ATPase pH 4.3 stain: Type 2C
• NADH stain: Dark
• Post-Regeneration
62. FIBRE REGENERATION:-
Regenerating muscle fibers: Grouped (Biopsy from child (< 10 years)) Size:
Small
Cytoplasm
• Basophilic
• NADH: Dark, irregularly stained
Nuclei: Large
H&E
NADH-TR
63. POST-REGENERATION
•Fiber size: Moderately varied
•Muscle fiber Cytoplasm: Some fibers with coarse stain on NADH
•Internal nuclei: Occasional muscle fibers
•Fiber types: Many 2C
• Clustered
• Varied frequencies in different fascicles
•Endomysium: Mildly increased in some areas
NADH-TR ATPase Ph 4.6
64. BMD: BIOPSY FROM ADULT MALE -TYPICAL OF
CHRONIC DYSTROPHIES
Endomysial connective tissue: Increased
Fiber size: Variable, with small rounded fibers and Internal nuclei
Largest muscle fibers: Hypertrophied
Occasional muscle fibers: Necrosis; Regeneration; Hypercontraction; Split
Type 2C fibers: Scattered, Many
H&E VvG
65. BMD:-
Dystrophin: Sarcolemmal staining Rod region (d): Absent, N- (b) & C-terminus (f):
Reduced but Present. Normal control on left; Becker MD patient on right
N-terminal region of dystrophin: (a & b; Dys-3 antibody)
Rod region of dystrophin (c & d; Dys-1 antibody)
C-terminal region of dystrophin (e & f; Dys-2 antibody)
SUDAN BLACK
66. LIMB GIRDLE DYSTROPHY:-
Light and electron microscopy findings in muscle biopsies. (A and B) Haematoxylin and eosin staining
muscle from affected Subject .In A, abnormal myonuclei with an ‘empty’ appearance (arrows).In B, note
three abnormal nuclei (arrows) within a myofibre at higher magnification (×1000). (C and D) Electron
micrographs showing non-branching tubular filaments 18–20 nm in diameter within a muscle fibre .Note
myelin and membranous bodies surrounding filaments (C), which are characteristic of rimmed vacuoles.
Original magnifications: ×21 000 and ×35 000.
67. FACIOSCAPULOHUMORAL DYSTROPHY:-
Pathologic review of muscle biopsy shows :-
• Atrophic and Hypertrophic Muscle fibres.
• Moth eaten or mottled fibres on oxidative stains.
• Endomycial and perimycial lymphocytic infiltrate.
• There is little fibre necrosis and regeneration.
68. MYOTONIC DYSTROPHY:-
Muscle biopsy shows:-
• Initial selective atrophy of type 1 fibers.
• Nuclear internalzation.
• Ring fibres- bonafied pathologic disturbance in MyD
Hypercontractility.
• In long standing cases fiber necrosis, regeneration & fibrosis
supervenes.
69. METABOLIC MYOPATHIES:-
Lipid storage disorder:-
• Due to deficiency of Carnitine, Carnitine Palmitoyltransferase.
• Defects of beta-oxidation.
• Triglyceride Storage Disorders.
oil red o
71. Mitochondrial Myopathy:-
Includes defects of substrate utilization, oxidative phosphorylation
and respiratory chain.
Eg:-
• MELAS
• MERRF
• Cytochrome C Deficiency
Gomori trichrome stain
72. Muscle fibers with mitochondrial
proliferation stain darkly for succinic
dehydrogenase (SDH).
SDH is the most sensitive stain for
detecting mitochondrial proliferation.
Sudan Black- Ragged red fibers often have
increased lipid
77. NEUROGENIC MYOPATHY:-
• Neuromuscular junction disorder
eg:-Myasthenia Gravis
Lambert-Eaton’s Syndrome
• Denervating disease
eg:-Amylotrophic Lateral Sclerosis
Infantile Spinal Muscular Atrophies
Statistically the most important neuromusclular disorder are neurogenic,
more than 80% of which are attributed to some form of peripheral nerve
disease
Effect of denervation in all adult neurogenic atrophies is same.
79. NADH-TR
-early denervation- random atrophy of both fibre mainly type 1.
-Angulated
-Small and later large groups of atrophied fibre
-Target fiber
ALS:
