Multiple myeloma is a cancer of plasma cells that produces abnormal proteins. It most commonly affects people over age 65 and is more common in African populations. Symptoms include bone pain, infections, anemia, kidney problems, and neurological issues. Diagnosis requires the presence of clonal plasma cells in bone marrow, monoclonal proteins in blood or urine, or biomarkers of malignancy. Initial tests evaluate for paraproteins, organ damage, tumor burden, and prognosis.
Plasma cell disorders is a difficult topic where most residents and students confuse with regarding to differentiating between various types of para-proteinemias or plasma cell dyscrasias. This simple presentation will highlight the key points in differentiating, diagnosing these orders. Initial management principles are discussed as well.
MULTIPLE MYELOMA -HEMATOLOGIC MALIGNANCY-DISEASE OF BONE MARROW - PLASMA CELL DISORDER
PATHOLOGY, .CLINICAL FEATURES , AND ITS MANAGMENT REFERENCE HARRISON
Plasma cell disorders is a difficult topic where most residents and students confuse with regarding to differentiating between various types of para-proteinemias or plasma cell dyscrasias. This simple presentation will highlight the key points in differentiating, diagnosing these orders. Initial management principles are discussed as well.
MULTIPLE MYELOMA -HEMATOLOGIC MALIGNANCY-DISEASE OF BONE MARROW - PLASMA CELL DISORDER
PATHOLOGY, .CLINICAL FEATURES , AND ITS MANAGMENT REFERENCE HARRISON
references
20th edition of Harrison's T.B. OF INTERNAL MEDICINE
Blood and Lymphatic Cancer: Targets and Therapy
Advances in the diagnosis and management
of lymphoma
Zachary H Word1
Matthew J Matasar1,2
Multiple myeloma(MM) is hematologic malignancy characterized by neoplastic proliferation of single clone of plasma cell in bone marrow engaged in production of monoclonal (M) protein.
multiple myloma
By: Nader Amir Al-assadi
Supervised by : Dr/ Ghazi Alariqe
taiz university
Multiple myeloma (MM) is a plasma cell malignancy in which monoclonal plasma cells proliferate in bone marrow, resulting in an over abundance of monoclonal para protein (M protein), destruction of bone, and displacement of other hematopoietic cell lines.
The precise etiology of MM has not yet been established.
Roles have been suggested for a variety of factors, including genetic causes, environmental or occupational causes,radiation, chronic inflammation, and infection .
AML:ACUTE MYELOID LEUKAEMIA
for medical colleges teaching faculty and students as well. it includes AML causes , histopathological slides of subclasses of Acute myeloid leukemia, classification , diagnosis, management modalities, complications .Acute leukemias are stem cell disorders characterized by malignant neoplastic proliferation and accumulation of immature and non functional hematopoietic cells in the bone marrow.
The neoplastic cells show increased proliferation and/or decreased apoptosis.
If the defect primarily affects the common myeloid progenitor (CMP) then it is called Acute myeloid leukemia.
Acute myeloid leukemia (AML) is a neoplastic disease characterized by infiltration of the blood, bone marrow, and other tissues by proliferative, clonal undifferentiated cells of the hematopoietic system.
AML is the result of a sequence of somatic mutations in a multipotential primitive hematopoietic cell or, in some cases, a more differentiated progenitor cell.
It can be slow growing or rapidly fatal.
AML is the predominant form of leukemia during the neonatal period
Incidence : 1.5/100,000/year in infants decreases to approximately 0.4 per 100,000 children ages 5 to 9 years, increases gradually to 1.0 persons per 100,000 until age 25 years, and thereafter increases exponentially until the rate reaches approximately 25/100,000 persons.
AML accounts for 15 to 20 percent of the acute leukemias in children and 80 percent of the acute leukemias in adults.
Men > Women (4.5 : 3)
HEREDITY
1) Chromosomal aneuploidy like Trisomy 21 noted in Down syndrome
2) Defective DNA repair, e.g., Fanconi anemia, Bloom syndrome, and Ataxia telangiectasia
3) Congenital neutropenia ie Kostmann syndrome
4) Germline mutations of CCAAT/enhancer-binding protein α (CEBPA), runt-related transcription factor 1 (RUNX1), and tumor protein p53 (TP53) have also been associated with a higher predisposition to AML
RADIATION
Peaks after 5 to 7 yrs of exposure.
Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people also exposed to alkylating agents.
CHEMICAL AND OTHER EXPOSURES
Exposure to benzene, plastic, rubber, petroleum products, paint, ethylene oxide, herbicides and pesticides can increase the risk.
Smoking can also increase the risk
DRUGS
Anticancer drugs are the leading cause of therapy-associated AML.
Alkylating agent–associated leukemias occur on average 4–6 years after exposure, and affected individuals have aberrations in chromosomes 5 and 7.
Topoisomerase II inhibitor–associated leukemias occur 1–3 years after exposure, and affected individuals often have aberrations involving chromosome 11q23.
Other agents like Chloramphenicol, phenylbutazone, and, less commonly, chloroquine and methoxypsoralen.
SYMPTOMS :
Present with nonspecific symptoms initially.
Fatigue is the first symptom
Fever with or without infection will be present in approximately 10% patients
Bleeding, easy bruising
occasional
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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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
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.
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
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.
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
1. Multiple Myeloma
Dr. Sayem Bin Latif
MD (Cardiology) Phase A Resident
Chittagong Medical College & Hospital
23 Sept 2018
sayembinlatif@gmail.com
2. Introduction
• Multiple myeloma is clonal plasma cell neoplasm
• Usually accompanied by monoclonal antibody production
• 1% of all cancer
• Median age 65 years
• Incidence higher in African populations
4. Gammopathy
• Gammopathy refers to over-production of one or more classes of
immunoglobulin.
• It may be polyclonal or monoclonal.
5. Monoclonal Gammopathy
• This term refers to the presence of a monoclonal immunoglobulin
band in the serum
• Monoclonal immunoglobulin band = M-protein or paraprotein
• Paraproteins are abnormal immunoglobulin produced by atypical
plasma cell.
• Monoclonal gammopathies/Paraproteinemia may occur in association
with normal or reduced levels of the other immunoglobulins.
6. Polyclonal Gammopathy
• A gammopathy in which there is heterogeneous increase in
immunoglobulins involving more than one cell line
• Normally serum immunoglobulin are polyclonal and represent the
combined output from millions of different plasma cells.
7.
8. Diseases associated with M-proteins/Paraprotein
Malignant or
uncontrolled production
• Multiple myeloma
• Waldenstrom's
macroglobulinaemia
• MGUS
• NHL
• Solitary plasmacytoma
• CLL
• Primary amyloidosis
• Heavy chain disease
Benign or
stable production
• Chronic cold haemagglutinin
disease
• RA
• SLE
• Transient (e.g. with infections)
• AIDS
• Gaucher's disease
• Rarely with some solid tumor
9. Subject Benign Malignant
Bence-Jones proteinuria Absent May be Present
S paraprotein concentration Usually <20 g/L
and stationary
Usually >20 g/L & rising
Serum free light chain ratio Normal Abnormal
Immunoparesis
(hypogamaglobinaemia)
Absent Present
Underlying lympho
proliferative
disease or myeloma
Absent Present
Bone lesions Absent Present
Plasma cells in marrow < 10% > 10%
Features of benign and malignant paraproteinaemia
10. Normal Plasma Cell
Derived from B cell.
Large cell
Oval or round
Cytoplasm – basophilic with
small granule
Nucleus - Round
- eccentric
- peri nuclear halo
- absent nucleoli
- Chromatin arranged in
coarse strand, gives rise to “cart
wheel” appearance.
19. MULTIPLE MYELOMA
Multiple myeloma (myelomatosis) is a neoplastic proliferation of
plasma cells.
Characterized by plasma cell accumulation in the bone marrow,
The presence of monoclonal protein in the serum and/or urine and
Related tissue damage in symptomatic pt.
20. Normal plasma cells are derived from B cells and produce
immunoglobulins which contain heavy and light chains.
Normal immunoglobulins are polyclonal, which means that a variety
of heavy chains are produced and each may be of kappa or lambda
light chain type.
21. In myeloma, plasma cells produce immunoglobulin of a single heavy
and light chain, a monoclonal protein commonly referred to as a
paraprotein.
In some cases only light chain is produced and this appears in the
urine as Bence Jones proteinuria.
22. Annual incidence of MM is 4 per 1,00,000
Blacks have nearly twice the incidence of whites.
Myeloma accounts for 1% of all malignancies in whites and 2% in
blacks
13% of all hematologic cancers in whites and 33% in blacks.
Etiology
23. The incidence of myeloma is highest in African Americans and Pacific
islanders; intermediate in Europeans and North American whites; and
lowest in developing countries including Asia.
Myeloma increases in incidence with age. The median age at diagnosis
is 70 years; it is uncommon under age 40.
Male > females
24. Myeloma occurred with increased frequency in those exposed to the
radiation of nuclear warheads in World War II after a 20-year latency.
Myeloma has been seen more commonly than expected among
farmers who use herbicides & insecticides; wood workers, leather
workers, and those exposed to petroleum products & benzene.
A variety of chromosomal alterations with prognostic significance has
been found in patients with myeloma; 13q14 deletions, 17p13
deletions, and translocations t(11;14)(q13;q32) and t(4;14)(p16;q32)
predominate.
25.
26.
27.
28.
29. C/F - Bone Lesion
Bone pain Due to --
Osteoporosis
Pathologic fractures
Lytic bone lesions
Hypercalcaemia
* Tumor expansion
* Production of osteoclast
activating factor
by tumor cell
* Production of osteoblast
inhibitory factors
30.
31. Bone pain is the most common symptom in myeloma, affecting
nearly 70% of patients.
The pain usually involves the back and ribs
Unlike the pain of metastatic carcinoma, which often is worse at
night, the pain of myeloma is precipitated by movement.
Persistent localized pain in a patient with myeloma usually signifies a
pathologic fracture.
32. MM cell Several cytokines, including IL-1, lymphotoxin,
VEGF, receptor activator of NF- B (RANK) ligand, macrophage
inhibitory factor MIP-1 α, and TNF
Osteoclast activating factors
↑ osteoclast activity
33. Renal failure (25% pt of MM)
The degree of renal failure is usually moderate, with a serum
creatinine lower than 4mg/dl.
In 10% cases pts with newly diagnosed MM have renal failure severe
enough to require dialysis from the time of diagnosis.
Tubular damage/ cast nephropathy associated with the excretion of
light chains is almost always present.
34. Normally, light chains are filtered, reabsorbed in the tubules, and
catabolized.
↑ light chains in tubule Tubular cells become overloaded
Light chain toxic effects
intracellular lysosomal enzymes.
Tubular damage results
35. The earliest manifestation of this tubular damage is the adult Fanconi
syndrome (a type 2 proximal renal tubular acidosis), with loss of
glucose and amino acids, as well as defects in the ability of the kidney
to acidify and concentrate the urine.
In myeloma kidney the typical feature consists of the presence of
myeloma casts, mainly composed of light chain in distal tubule &
collecting ducts.
Cast formation ∝ severity of renal failure
36. Micrograph showing myeloma cast nephropathy in a kidney
biopsy. Hyaline casts are PAS positive (dark pink/red - right of
image). Myelomatous casts are PAS negative (pale pink - left of
image). PAS stain.
37. INFECTIONS
Next to bone pain, most common clinical problem in patients with
myeloma is susceptibility to bacterial infections.
The most common infections are pneumonia and pyelonephritis.
Most frequent pathogens are Streptococcus pneumoniae,
Staphylococcus aureus, and Klebsiella pneumoniae in the lungs.
38. INFECTIONS - Why there is increased chance of
infection/ immune deficiency ?
Patients with myeloma have diffuse hypogammaglobulinemia if the M
component is excluded.
The hypogammaglobulinemia is related to both decreased production and
increased destruction of normal antibodies.
Some patients generate a population of circulating regulatory cells in
response to their myeloma that can suppress normal antibody synthesis.
39. In the case of IgG myeloma, normal IgG antibodies are broken down
more rapidly than normal because the catabolic rate for IgG antibodies
varies directly with the serum concentration.
The large M component results in fractional catabolic rates of 8–16%
instead of the normal 2%.
These patients have very poor antibody responses, especially to
polysaccharide antigens such as those on bacterial cell walls.
40. Granulocyte lysozyme content is low.
Granulocyte migration is not as rapid as normal in patients with
myeloma, probably the result of a tumor product.
Abnormalities in complement functions in myeloma patients.
Some commonly used therapeutic agents, e.g., dexamethasone,
suppress immune responses and increase susceptibility to infection.
41. Anaemia & Bone marrow failure
Normocytic and normochromic anemia occurs in 80% of myeloma
patients.
A larger than expected fraction of patients may have megaloblastic
anemia due to either folate or vitamin B12 deficiency.
42. Causes of anaemia -
Replacement of normal marrow by expanding tumor cells
Inhibition of hematopoiesis by factors made by the tumor
Reduced production of erythropoietin by the kidney.
Mild hemolysis.
Chemotherapy with cytotoxic agents.
43. Granulocytopenia and thrombocytopenia are very rare except when therapy-
induced.
Clotting abnormalities may be seen due to -
The failure of antibody-coated platelets to function properly or
The interaction of the M component with clotting factors I, II, V,
VII, or VIII.
Deep venous thrombosis is also observed with use of thalidomide or
lenalidomide in combination with dexamethasone.
44. Raynaud's phenomenon and impaired circulation may result if the M component
forms cryoglobulins.
Hyperviscosity syndromes may develop depending on the physical properties of
the M component (most common with IgM, IgG3, and IgA paraproteins).
45. Neurological Symptom
Neurological feature Cause
lethargy, weakness, depression, and
confusion.
Hypercalcemia
Headache, fatigue, visual
disturbances, and retinopathy.
Hyperviscosity
Radicular pain, and loss of bowel and
bladder control.
Cord compression due to Bony
damage and collapse
Sensory neuropathy side effect of thalidomide and
bortezomib therapy
46. In case of spinal cord compression, dorsal spine is the most common
site of involvement, followed by the lumbar region.
So clinical picture of spinal cord compression consists of back pain &
paraparesis.
Lumbar involvement can cause a cauda equina syndrome ( LBP with
radicular distribution & leg weakness)
48. Rare presentations
• Soft tissue or solitary bone masses (plasmacytomas)
• Hyperviscosity-induced arterial infarctions or venous thrombosis
• Concomitant amyloidosis with gastrointestinal symptoms, peripheral
neuropathy, or cardiomegaly
49. Medical emergencies of MM
Cord compression
Pathologic fractures
Hyperviscosity
Sepsis
Hypercalcemia
50.
51. Classic triad of myeloma
Marrow plasmacytosis (>10%)
- Bone marrow plasma cells are CD138+ and monoclonal
- If flow cytometry is performed, most plasma cells (>90%) will
show a "neoplastic" phenotype
Lytic bone lesions
A serum and/or urine M component.
53. The revised IMWG criteria allow, in addition to the classic CRAB
features, three “myeloma defining events” (MDEs).
The presence of at least one of these markers is considered
sufficient for a diagnosis of multiple myeloma, regardless of the
presence or absence of symptoms or CRAB features.
54. The new definition of active multiple myeloma is:
• 1. Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or
extramedullary plasmacytoma and any one or more of the following
CRAB features and myeloma-defining events:
• 2. Evidence of end organ damage that can be attributed to the
underlying plasma cell proliferative disorder, specifically:
• Hypercalcemia: serum calcium >0.25 mmol/L (>1mg/dL) higher than
the upper limit of normal or >2.75 mmol/L (>11mg/dL)
55. • Renal insufficiency: creatinine clearance <40 mL per minute or serum
creatinine >177µmol/L (>2mg/dL)
• Anemia: hemoglobin valure of >20g/L below the lowest limit of
normal, or a hemoglobin value <100g/L
• Bone lesions: one or more osteolytic lesion on skeletal radiography,
CT, or PET/CT. If bone marrow has <10% clonal plasma cells, more
than one bone lesion is required to distinguish from solitary
plasmacytoma with minimal marrow involvement
56. • 3. Any one or more of the following biomarkers of malignancy (MDEs):
• 60% or greater clonal plasma cells on bone marrow examination
• Serum involved / uninvolved free light chain ratio of 100 or greater,
provided the absolute level of the involved light chain is at least 100mg/L
(a patient’s “involved” free light chain—either kappa or lambda—is the one
that is above the normal reference range; the “uninvolved” free light chain
is the one that is typically in, or below, the normal range)
• More than one focal lesion on MRI that is at least 5mm or greater in size.
57. Initial Investigations in Patients with Myeloma
Screening tests
Tests to establish diagnosis.
Tests to estimate tumour burden and prognosis.
Tests to assess myeloma related organ impairment (ROTI).
Special tests indicated in some patients.
58. Ix – For Presence of a paraprotein
• Serum and urine should be screened by immunoglobulin
electrophoresis.
59.
60. • CBC : - There is usually a normochromic normocytic or macrocytic
anaemia.
- Neutropenia and thrombocytopenia occur in advanced
disease
• PBF : -Rouleaux formation is marked in most cases.
- Abnormal plasma cells appear in the blood film in 15% of
patients and can be detected by sensitive flow cytometry in over 50%.
• ESR : Raised
• CRP : Raised
61. Bone marrow Aspiration: Increased plasma cells (usually >20%)
often with abnormal forms
Sermn calcium : elevation occurs in 45% of patients.
Serum alkaline phosphatase : Typically normal, because of the
absence of osteoblastic activity (except following pathological
fractures).
62. Serum creatinine : raised in 20% of cases.
Serum albumin : decreased in advanced disease.
Serum ϐ2-microglobulin: often raised and is a useful indicator of
prognosis. Levels less than 4 mg/L imply a relatively good prognosis.
63. Radiological investigation
Reveals osteolytic areas without evidence of surrounding osteoblastic
reaction or sclerosis in 60% of patients.
Generalized osteoporosis in 20%.
Pathological fractures or vertebral collapse are common.
64.
65.
66.
67. Tests to estimate tumour burden and
prognosis
FISH analysis
Quantification of Monoclonal protein in serum and urine
Albumin
β2-microglobulin
Skeletal survey
68.
69.
70.
71. Staging systems for patients with myeloma
Based on a variety of clinical and laboratory tests, unlike the anatomic
staging systems for solid tumors.
Serum β2-microglobulin is the single most powerful predictor of
survival and can substitute for staging.
β2-Microglobulin is a protein of 11,000 mol wt with homologies to
the constant region of immunoglobulins that is the light chain of the
class I major histocompatibility antigens (HLA-A, -B, -C) on the
surface of every cell.
74. Prognosis : Stage IA have a median survival of >5 years and
those in stage IIIB about 15 months.
Limitation : This staging system has been found not to predict
prognosis after treatment with high-dose therapy or the novel targeted
therapies that have emerged.
76. International Staging Systems (ISS)/
International Prognostic Index (IPI)
for patients with myeloma
Factors Stage Median
Survival,
Months
β2M < 3.5,
alb ≥3.5
I (28%) 62
β2M < 3.5,
alb < 3.5 or
β2M = 3.5–5.5
II (39%) 44
β2M > 5.5 III (33%) 29