This document discusses various types of white blood cells and abnormalities seen in peripheral blood smears and bone marrow aspirates. It provides images and descriptions of neutrophils, lymphocytes, monocytes, eosinophils, basophils, as well as abnormal cells seen in conditions like leukemia, multiple myeloma, megaloblastic anemia, and more. It also discusses hematopoiesis, the process of blood cell production and differentiation, and factors that regulate this process.
Automated histopathological image analysis: a review on ROI extractioniosrjce
IOSR Journal of Computer Engineering (IOSR-JCE) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of computer engineering and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in computer technology. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Urine analysis is an integral part of a clinical laboratory. automation techniques in urine biochemistry, their priniciplas and microscopy along with their advantages and disadvantages are outlined.
Cell blocks are an integral part of cytology preparations and ancillary testing.
In certain settings, such as molecular testing of lung cancer or by a commercial laboratory, they are the preferred cytology preparation.
To optimize them, care in specimen procurement, triage, and improvement in current processing techniques are necessary.
Fluid cytology in serous cavity effusionstashagarwal
The intrathoracic and intraperitoneal organs are covered by a single layer of mesothelial cells, which is continuous with the lining of the thoracic and peritoneal cavities. The potential space between the two layers of epithelium contains a small amount of lubricating fluid.
Serous fluid lies between the membranes lining the body cavities(parietal) and those covering the organs within the cavities(visceral).
Production and reabsorption are normally at a constant rate. They are influenced by
Changes in osmotic and hydrostatic pressure in the blood.
Concentration of chemical constituents in the plasma
Permeability of blood vessels and membranes.
An accumulation of fluid, called an effusion, results from an imbalance of fluid production and reabsorption. This fluid accumulation in the pleural, pericardial, and peritoneal cavities is known as serous effusion.
This presentation in mainly focused of understanding of automation and its utility in cytopathology. It will be very usefull for postgraduate in pathology, cytopathologist and cytotechnicians.
This presentation describes the technique of bone marrow aspiration and biopsy and shows the maturation of elements in sequence and finally adds a note on how to report a bone marrow slide
Automated histopathological image analysis: a review on ROI extractioniosrjce
IOSR Journal of Computer Engineering (IOSR-JCE) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of computer engineering and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in computer technology. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Urine analysis is an integral part of a clinical laboratory. automation techniques in urine biochemistry, their priniciplas and microscopy along with their advantages and disadvantages are outlined.
Cell blocks are an integral part of cytology preparations and ancillary testing.
In certain settings, such as molecular testing of lung cancer or by a commercial laboratory, they are the preferred cytology preparation.
To optimize them, care in specimen procurement, triage, and improvement in current processing techniques are necessary.
Fluid cytology in serous cavity effusionstashagarwal
The intrathoracic and intraperitoneal organs are covered by a single layer of mesothelial cells, which is continuous with the lining of the thoracic and peritoneal cavities. The potential space between the two layers of epithelium contains a small amount of lubricating fluid.
Serous fluid lies between the membranes lining the body cavities(parietal) and those covering the organs within the cavities(visceral).
Production and reabsorption are normally at a constant rate. They are influenced by
Changes in osmotic and hydrostatic pressure in the blood.
Concentration of chemical constituents in the plasma
Permeability of blood vessels and membranes.
An accumulation of fluid, called an effusion, results from an imbalance of fluid production and reabsorption. This fluid accumulation in the pleural, pericardial, and peritoneal cavities is known as serous effusion.
This presentation in mainly focused of understanding of automation and its utility in cytopathology. It will be very usefull for postgraduate in pathology, cytopathologist and cytotechnicians.
This presentation describes the technique of bone marrow aspiration and biopsy and shows the maturation of elements in sequence and finally adds a note on how to report a bone marrow slide
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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.
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.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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
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
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
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.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
2. In the center of the field are a band neutrophil on the left and a segmented
neutrophil on the right. 2CSBRP-Sep-2011
3. A normal mature lymphocyte is seen on the left compared to a segmented
PMN on the right. An RBC is seen to be about 2/3 the size of a normal
lymphocyte. 3CSBRP-Sep-2011
4. Here is a monocyte. It is slightly larger than a lymphocyte and has a folded nucleus.
Monocytes can migrate out of the bloodstream and become tissue macrophages under
the influence of cytokines. Note the many small smudgy blue platelets between the
RBC's
4
CSBRP-Sep-2011
5. In the center of the field is an eosinophil with a bilobed nucleus and numerous
reddish granules in the cytoplasm. Just underneath it is a small lymphocyte.
Eosinophils can increase with allergic reactions and with parasitic infestations. 5
CSBRP-Sep-2011
6. There is a basophil in the center of the field which has a lobed nucleus (like PMN's) and numerous
coarse, dark blue granules in the cytoplasm. They are infrequent in a normal peripheral blood
smear, and their significance is uncertain. A band neutrophil is seen on the left, and a large,
activated lymphocyte on the right.
6
CSBRP-Sep-2011
11. This hypersegmented neutrophil is present along with macro-ovalocytes in a
case of pernicious anemia. Compare the size of the RBC's to the lymphocyte at
the lower left center.
11CSBRP-Sep-2011
14. The RBC's in the background appear normal. The important finding here is the
presence of many PMN's. An elevated WBC count with mainly neutrophils suggests
inflammation or infection. A very high WBC count (>50,000) that is not a leukemia is
known as a "leukemoid reaction". This reaction can be distinguished from malignant
WBC's by the presence of large amounts of leukocyte alkaline phosphatase (LAP) in
the normal neutrophils.
14CSBRP-Sep-2011
15. The RBC's here are smaller than normal and have an increased zone of central pallor.
This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller
size of each RBC) anemia. There is also increased anisocytosis (variation in size) and
poikilocytosis (variation in shape). 15CSBRP-Sep-2011
16. Here is a hypersegmented neutrophil that is present with megaloblastic
anemias. There are 8 lobes instead of the usual 3 or 4. Such anemias can
be due to folate or to B12 deficiency. The size of the RBC's is also
increased (macrocytosis, which is hard to appreciate in a blood smear).
16CSBRP-Sep-2011
17. The nucleated RBC in the center contains basophilic stippling of the
cytoplasm. This suggests a toxic injury to the bone marrow. Such
stippling may also appear with severe megaloblastic anemia.
17CSBRP-Sep-2011
18. The WBC's seen here are "atypical" lymphocytes. They are atypical
because they are larger (more cytoplasm) and have nucleoli in their
nuclei. The cytoplasm tends to be indented by surrounding RBC's. Such
atypical lymphocytes are often associated with infectious
18CSBRP-Sep-2011
19. If most of the neutrophils appear bilobed, this is indicative of an uncommon condition
known as Pelger-Huet anomaly, an inherited condition. This is the heterozygous form.
The homozygous form is fatal. Just be aware of this condition when you get back a
manual differential count with mostly bands, but the WBC count is normal or the
patient shows no signs of infection or inflammation. 19CSBRP-Sep-2011
20. Here is another view of a peripheral blood smear in a patient with CML. Often, the
numbers of basophils and eosinophils, as well as bands and more immature myeloid
cells (metamyelocytes and myelocytes) are increased. Unlike AML, there are not many
blasts with CML.
20CSBRP-Sep-2011
21. Here is a smear of bone marrow aspirate from a patient with multiple myeloma. Note
that there are numerous well-differentiated plasma cells with eccentric nuclei and a
perinuclear halo of clearer cytoplasm. There is also an abnormal plasma cell with a
double nucleus.
21CSBRP-Sep-2011
22. This is a normal plasma cell as seen in a bone marrow smear at high magnification.
Note the eccentric nucleus as well as the perinuclear halo containing the Golgi
apparatus. The remaining cytoplasm containing abundant rough endoplasmic reticulum
is dark blue.
22CSBRP-Sep-2011
23. A history of recurrent bacterial infections and giant granules seen in peripheral blood leukocytes
is characteristic for Chediak-Higashi syndrome. This disorder results from a mutation in the
LYST gene on chromosome 1q42 that encodes a protein involved in intracecellular trafficking of
proteins. Microtubules fail to form properly, and the neutrophils do not respond to chemotactic
stimuli. Giant lysosomal granules fail to function. Soft tissue abscesses with Staphylococcus
aureus are common. Other cells affected by this disorder include platelets (bleeding),
melanocytes (albinism), Schwann cells (neuropathy), NK and cytotoxic T cells (aggressive
lymphoproliferative disorder).
23CSBRP-Sep-2011
25. An example of a CBC with automated WBC differential count is shown above.
The absolute numbers for total WBC count and each type of leukocyte are in
thousands per cubic millimeter (or alternatively, per microliter). 25CSBRP-Sep-2011
26. Absolute counts
The absolute white blood cell counts are most useful, and
are calculated by multiplying the % of each cell type
counted by the total WBC count. Simple percentages
may be misleading, since an apparent percentage
increase in one constituent may actually be due to a
significant and absolute decrease of another type of
WBC. For example, 99% lymphs with an absolute WBC
count of 1300/microliter means neutropenia, not
lymphocytosis. Always consider the WBC percentages in
the context of the total WBC count.
26CSBRP-Sep-2011
28. HematopoiesisHematopoiesis
• Upto 2months --- Yolk sac
• Upto 7th
month --- Liver
• After 7th
month --- BM major site
(starts producing from 3rd
month)
• At birth --- BM is the only site
28CSBRP-Sep-2011
29. • Distribution of hemopoietic BM
in children and adults.
HematopoiesisHematopoiesis
29CSBRP-Sep-2011
30. HematopoiesisHematopoiesis
• Two critical properties of STEM CELLs:
1-Self Renewal
(regenerate their own population) &
2-Differentiate towards matured cells
30CSBRP-Sep-2011
31. • Hemopoietic stem cells (HSCs)
- have great capacity for self renewal
- Pleuripotent
- most of them are not in cycle
• Committed progenitors (lineage restricted)
- self renewal is very limited
- there after a fraction divide actively
- they acively generate matured cells
• Early recognizable precursors (ex: Mye.blast, Proerythroblast)
- cannot self renew
- proliferate, differentiate and die
HematopoiesisHematopoiesis
31CSBRP-Sep-2011
33. HematopoiesisHematopoiesis
• Stem cell proliferation and differentiation
-- is mediated by many soluble factors
-- stem cell and stromal cell interaction in BM
33CSBRP-Sep-2011
34. Examples for soluble factors:
c-kit and FLT-3 ligand at stem cell level
GM-CSF at CFU-GM level
Clinical application:
some of the factors are available by recombinant
technology for therapeutic use include:
1. EPO
2. GM-CSF
3. G-CSF
4. TPO
HematopoiesisHematopoiesis
34CSBRP-Sep-2011
36. Stem cell and stromal cell interaction:
BONE MARROW
MICROENVIRONMENT
HematopoiesisHematopoiesis
36CSBRP-Sep-2011
37. HematopoiesisHematopoiesis
BONE MARROW MICROENVIRONMENT
BM is a vast network of thin walled BVs
(sinusoids) lined by
--single layer of endothelium and
--discontinuous basement membrane
--and adventitial cells.
--extracellular matrix (cell adhesion proteins-
fibronectin, laminin, Type-IV collagen,
hemonectin & glycosaminoglycans)
37CSBRP-Sep-2011
38. BONE MARROW MICROENVIRONMENT
Erythroblasts and also progenitors exhibit
the property of adherence to stromal cells.
This is mainly mediated by Fibronectin
When the cells differentiate they become
non-adherent
HematopoiesisHematopoiesis
38CSBRP-Sep-2011
43. Neutrophilia
An increase in the absolute neutrophil count, it can be
increased transiently with stress and exercise by a
shift of neutrophils from the marginating pool to the
circulating pool. Pathologic processes that result in
neutrophilia include:
• Infection
• Toxins: metabolic (uremia), drugs, chemicals
• Tissue destruction or necrosis: infarction, burns, neoplasia,
etc
• Hemorrhage, especially into a body cavity
• Rapid hemolysis
• Hematologic disorders: leukemias, myeloproliferative
disorders
43CSBRP-Sep-2011
44. Neutropenia
– A decrease in the absolute neutrophil count. Pathologic processes that
result in neutropenia include processes that decrease production or
increase destruction. Diseases that decrease neutrophil production
include:
• Aplastic anemia
• Toxins that damage marrow
• Collagen vascular diseases (such as SLE)
• Myelphthisic marrow processes such as marrow infiltration by infections or
metastatic carcinomas
• Hematologic malignancies such as leukemias
• Myeloproliferative disorders
• Radiation therapy
• Chemotherapy
• Congenital disorders
– Diseases that increase neutrophil destruction include:
• Splenomegaly with hypersplenism
• Infection
• Immune destruction
44CSBRP-Sep-2011
45. Lymphocytosis
– An increase in the number of circulating lymphocytes
may normally be observed in infants and young
children. Pathologic processes with lymphocytosis
may include:
• Acute infections, including pertussis, typhoid, and
paratyphoid
• Infectious mononucleosis, with "atypical" lymphocytosis
• Viral infections, including measles, mumps, adenovirus,
enterovirus, and Coxsackie virus
• Toxoplasmosis
• HTLV I
45CSBRP-Sep-2011
46. Lymphopenia
– A decrease in the number of circulating
lymphocytes may be seen with:
• Immunodeficiency syndromes, including congenital
(DiGeorge syndrome, etc) and acquired (AIDS)
conditions
• Corticosteroid therapy
• Neoplasia, including Hodgkin's disease, non-
Hodgkin's lymphomas, and advanced carcinomas
• Radiation therapy
• Chemotherapy
46CSBRP-Sep-2011
47. Monocytosis
• An increase in the number of circulating
monocytes may be seen with:
– Infections: such as brucellosis, tuberculosis and
rickettsia, Bacterial endocarditis
– Myeloproliferative disorders
– Hodgkin's disease
– Gastrointestinal disorders, including inflammatory
bowel diseases and sprue
47CSBRP-Sep-2011
48. Monocytopenia
• A decrease in the number of circulating
monocytes may be seen with:
– Early corticosteroid therapy
– Hairy cell leukemia
48CSBRP-Sep-2011
49. Eosinophilia
• An absolute increase in the number of
circulating eosinophils may occur with:
– Allergic drug reactions
– Parasitic infestations, especially those with tissue
invasion
– Extrinsic asthma
– Hay fever
– Extrinsic allergic alveolitis ("farmer's lung")
– Chronic infections
– Hematologic malignancies: CML, Hodgkin's disease
49CSBRP-Sep-2011
50. Eosinopenia
• An absolute decrease in the number of
circulating eosinophils may occur with:
– Acute stress reactions with increased
glucocorticoid and epinephrine secretion
– Acute inflammation
– Cushing's syndrome with corticosteroid
therapy
50CSBRP-Sep-2011
51. Basophilia and Basopenia
– An absolute increase in the number of
circulating basophils may occur with
myeloproliferative disorders and with some
allergic reactions.
– An absolute decrease in the number of
circulating basophils may occur with the same
conditions that lead to eosinopenia
51CSBRP-Sep-2011
52. Left shift An absolute increase in neutrophils with an increase in bands, and
sometimes an increase in immature forms such as metamyelocytes
or myelocytes
Hypersegmentation Polymorphonuclear leukocytes normally have 3 or 4 lobes, but 5 or
6 or more lobes indicate hypersegmentation; seen most often with
megaloblastic anemias, sometimes with myeloproliferative
disorders, or following chemotherapy (methotrexate)
Toxic granules Increased number and prominence of the azurophilic (primary)
granules; seen most often with bacterial infections and in
association with cytoplasmic vacuolization
Döhle body Irregularly shaped blue staining area in the cytoplasm due to free
ribosomes or RER; seen with infections
Smudge cell / Basket cell A ruptured cell remnant, classically associated with fragile
lymphocytes in CLL
Pelger-Huet anomaly An autosomal dominant condition with neutrophils that are mostly
bilobed in the heterozygote (normal function) and unilobate in the
homozygote (fatal )
May-Hegglin anomaly Rare disorder with large, prominent Döhle-like bodies
Chediak-Higashi syndrome Rare disorder with large neutrophilic granules representing
abnormal lysosomes
52CSBRP-Sep-2011
53. Agranulocytosis
• Deficiency of granulocytes
• Recognised as a distinct entity in
1922
• Drugs are the common culprits
• Early recognition is associated with
good prognosis
53CSBRP-Sep-2011
54. Symptomatology:
• Chills & fever
• Extreme prostration
• Ulceration of gums, tonsils, soft
palate, tongue, pharynx (in severe cases
ulcerations may be gangrenous)
• Sepsis
• Death
Agranulocytosis
54CSBRP-Sep-2011
55. Drugs that are associated with AGC:
1. Analgesics: phenylbutazone, phenacetin,
indimethacin, acetyl salicylic acid,
ibuprofen
2. Antiepileptics: barbiturates, hydantoin
3. Antibacterials: chloramphenicol,
vancomycin, INH, PAS
4. Miscellaneous: penicillamine, cimetidine,
quinine, gold salts
5. Chemicals: benzene
Agranulocytosis
55CSBRP-Sep-2011
56. Mechanism: Immunologically mediated
Evidences:
1-Reintroduction of the drug is associated with
reduction in polys
2-Serum from the patient, reduces the granulocyte
count in normal persons
3-Patient’s serum lysed granulocytes in vitro
Agranulocytosis
56CSBRP-Sep-2011
57. Hematological findings:
1. Deficiency of granulocytes
2. No anemia
3. No thrombocytopenia
4. BM may show mild hypoplasia
Agranulocytosis
57CSBRP-Sep-2011
58. Monitoring blood counts is mandatory
when the following drugs are used:
1. Gold salts
2. Thiouracil
3. Anticancer drugs
Agranulocytosis
58CSBRP-Sep-2011
In the center of the field are a band neutrophil on the left and a segmented neutrophil on the right.
A normal mature lymphocyte is seen on the left compared to a segmented PMN on the right. An RBC is seen to be about 2/3 the size of a normal lymphocyte.
Here is a monocyte. It is slightly larger than a lymphocyte and has a folded nucleus. Monocytes can migrate out of the bloodstream and become tissue macrophages under the influence of cytokines. Note the many small smudgy blue platelets between the RBC's.
In the center of the field is an eosinophil with a bilobed nucleus and numerous reddish granules in the cytoplasm. Just underneath it is a small lymphocyte. Eosinophils can increase with allergic reactions and with parasitic infestations.
There is a basophil in the center of the field which has a lobed nucleus (like PMN's) and numerous coarse, dark blue granules in the cytoplasm. They are infrequent in a normal peripheral blood smear, and their significance is uncertain. A band neutrophil is seen on the left, and a large, activated lymphocyte on the right.
This hypersegmented neutrophil is present along with macro-ovalocytes in a case of pernicious anemia. Compare the size of the RBC's to the lymphocyte at the lower left center.
The size of many of these RBC's is quite small, with lack of the central zone of pallor. These RBC's are spherocytes. In hereditary spherocytosis, there is a lack of spectrin, a key RBC cytoskeletal membrane protein. This produces membrane instability that forces the cell to the smallest volume--a sphere. In the laboratory, this is shown by increased osmotic fragility. The spherocytes do not survive as long as normal RBC's. With hemolysis, there is increased RBC production, evidenced by the reticulocyte at the upper left center.
A manual WBC differential count is performed by having a person trained in peripheral blood morphology review the stained blood smear and manually count 100 white cells (or 50 cells in the case of severe leukopenia). The major advantage is that the observer can determine subtle differences in morphology and observe additional changes in RBC morphology and platelets. The major disadvantage is the need for a trained person to spend increased time (with increased cost) needed to scan the smears. Also, there can be some inter-observer variation.
A standard complete blood count is performed on an automated laboratory instrument that quantitates the number of WBC's present. Some instruments are also able to perform an "automated" WBC count. The advantages of the automated WBC differential are speed, low cost per test, and the precision from the large number of cells counted. The disadvantages include the initial cost of buying the instrument, inability to distinguish subtle differences in morphology, more marked abnormalities, and lack of information about RBC's or platelets.
An example of a CBC with automated WBC differential count is shown above. The absolute numbers for total WBC count and each type of leukocyte are in thousands per cubic millimeter (or alternatively, per microliter).
In children almost all bones are involved in hemopoiesis and in adults it is confined to calvaria, upper ends of humori, femora, pelvic bones, vertebraand rib cage. In adults distribution mimics “a person wearing T-shirt, a cap and shorts”.
HSCs have two essential properties that are required for the maintenance of hematopoiesis: pluripotency and the capacity for self-renewal. Pluripotency refers to the ability of a single HSC to generate all mature hematopoietic cells. When an HSC divides at least one daughter cell must self-renew to avoid stem cell depletion. Self-renewing divisions are believed to occur within a specialized marrow niche, in which stromal cells and secreted factors nurture and somehow maintain the HSCs.[2] As you may have already surmised from their ability to migrate during embryonic development, HSCs are not sessile. Particularly under conditions of marked stress, such as severe anemia, HSCs are mobilized from the bone marrow and appear in the peripheral blood. In such circumstances, additional HSC niches are sometimes induced or “unveiled” in other tissues, such as the spleen and liver, which can then become sites of extramedullary hematopoiesis.
The marrow response to short-term physiologic needs is regulated by hematopoietic growth factors through effects on the committed progenitors. Since mature blood elements are terminally differentiated cells with finite life spans, their numbers must be constantly replenished. In at least some divisions of HSCs, a single daughter cell begins to differentiate. Once past this threshold, these newly committed cells lose the capacity for self-renewal and commence an inexorable journey down a road that leads to terminal differentiation and death. However, as these progenitors differentiate they also begin to express receptors for lineage-specific growth factors, which stimulate their short-term growth and survival. Some growth factors, such as stem cell factor (also called c-KIT ligand) and FLT3-ligand, act on very early committed progenitors. Others, such as erythropoietin, granulocyte-macrophage colonystimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and thrombopoietin, act on committed progenitors with more restricted potentials. Feedback loops that are mediated through growth factors tune the marrow output, allowing the numbers of formed blood elements (red cells, white cells, and platelets) to be maintained within appropriate ranges.
FIGURE 13-1 Differentiation of blood cells. CFU, colony forming unit; SCF, stem cell factor; Flt3L, Flt3 ligand; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; LIN–, negative for lineage-specific markers; M-CSF, macrophage colony-stimulating factor. Robbin’spath 8th Ed.
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HSCs have two essential properties that are required for the maintenance of hematopoiesis: pluripotency and the capacity for self-renewal. Pluripotency refers to the ability of a single HSC to generate all mature hematopoietic cells. When an HSC divides at least one daughter cell must self-renew to avoid stem cell depletion. Self-renewing divisions are believed to occur within a specialized marrow niche, in which stromal cells and secreted factors nurture and somehow maintain the HSCs.[2] As you may have already surmised from their ability to migrate during embryonic development, HSCs are not sessile. Particularly under conditions of marked stress, such as severe anemia, HSCs are mobilized from the bone marrow and appear in the peripheral blood. In such circumstances, additional HSC niches are sometimes induced or “unveiled” in other tissues, such as the spleen and liver, which can then become sites of extramedullary hematopoiesis.
The marrow response to short-term physiologic needs is regulated by hematopoietic growth factors through effects on the committed progenitors. Since mature blood elements are terminally differentiated cells with finite life spans, their numbers must be constantly replenished. In at least some divisions of HSCs, a single daughter cell begins to differentiate. Once past this threshold, these newly committed cells lose the capacity for self-renewal and commence an inexorable journey down a road that leads to terminal differentiation and death. However, as these progenitors differentiate they also begin to express receptors for lineage-specific growth factors, which stimulate their short-term growth and survival. Some growth factors, such as stem cell factor (also called c-KIT ligand) and FLT3-ligand, act on very early committed progenitors. Others, such as erythropoietin, granulocyte-macrophage colonystimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and thrombopoietin, act on committed progenitors with more restricted potentials. Feedback loops that are mediated through growth factors tune the marrow output, allowing the numbers of formed blood elements (red cells, white cells, and platelets) to be maintained within appropriate ranges.
FIGURE 13-1 Differentiation of blood cells. CFU, colony forming unit; SCF, stem cell factor; Flt3L, Flt3 ligand; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; LIN–, negative for lineage-specific markers; M-CSF, macrophage colony-stimulating factor. Robbin’spath 8th Ed.
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HSCs have two essential properties that are required for the maintenance of hematopoiesis: pluripotency and the capacity for self-renewal. Pluripotency refers to the ability of a single HSC to generate all mature hematopoietic cells. When an HSC divides at least one daughter cell must self-renew to avoid stem cell depletion. Self-renewing divisions are believed to occur within a specialized marrow niche, in which stromal cells and secreted factors nurture and somehow maintain the HSCs.[2] As you may have already surmised from their ability to migrate during embryonic development, HSCs are not sessile. Particularly under conditions of marked stress, such as severe anemia, HSCs are mobilized from the bone marrow and appear in the peripheral blood. In such circumstances, additional HSC niches are sometimes induced or “unveiled” in other tissues, such as the spleen and liver, which can then become sites of extramedullary hematopoiesis.
The marrow response to short-term physiologic needs is regulated by hematopoietic growth factors through effects on the committed progenitors. Since mature blood elements are terminally differentiated cells with finite life spans, their numbers must be constantly replenished. In at least some divisions of HSCs, a single daughter cell begins to differentiate. Once past this threshold, these newly committed cells lose the capacity for self-renewal and commence an inexorable journey down a road that leads to terminal differentiation and death. However, as these progenitors differentiate they also begin to express receptors for lineage-specific growth factors, which stimulate their short-term growth and survival. Some growth factors, such as stem cell factor (also called c-KIT ligand) and FLT3-ligand, act on very early committed progenitors. Others, such as erythropoietin, granulocyte-macrophage colonystimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and thrombopoietin, act on committed progenitors with more restricted potentials. Feedback loops that are mediated through growth factors tune the marrow output, allowing the numbers of formed blood elements (red cells, white cells, and platelets) to be maintained within appropriate ranges.
The bone marrow is a unique microenvironment that supports the orderly proliferation, differentiation, and release of blood cells. It is filled with a network of thin-walled sinusoids lined by a single layer of endothelial cells, which are underlaid by a discontinuous basement membrane and adventitial cells. Within the interstitium lie clusters of hematopoietic cells and fat cells. Differentiated blood cells enter the circulation by transcellular migration through the endothelial cells.
The normal marrow is organized in subtle, but important, ways. For example, normal megakaryocytes lie next to sinusoids and extend cytoplasmic processes that bud off into the bloodstream to produce platelets, while red cell precursors often surround macrophages (so-called nurse cells) that provide some of the iron needed for the synthesis of hemoglobin. Diseases that distort the marrow architecture, such as deposits of metastatic cancer or granulomatous disease, can cause the abnormal release of immature precursors into the peripheral blood, a finding that is referred to as leukoerythroblastosis
The bone marrow is a unique microenvironment that supports the orderly proliferation, differentiation, and release of blood cells. It is filled with a network of thin-walled sinusoids lined by a single layer of endothelial cells, which are underlaid by a discontinuous basement membrane and adventitial cells. Within the interstitium lie clusters of hematopoietic cells and fat cells. Differentiated blood cells enter the circulation by transcellular migration through the endothelial cells.
The normal marrow is organized in subtle, but important, ways. For example, normal megakaryocytes lie next to sinusoids and extend cytoplasmic processes that bud off into the bloodstream to produce platelets, while red cell precursors often surround macrophages (so-called nurse cells) that provide some of the iron needed for the synthesis of hemoglobin. Diseases that distort the marrow architecture, such as deposits of metastatic cancer or granulomatous disease, can cause the abnormal release of immature precursors into the peripheral blood, a finding that is referred to as leukoerythroblastosis
The bone marrow is a unique microenvironment that supports the orderly proliferation, differentiation, and release of blood cells. It is filled with a network of thin-walled sinusoids lined by a single layer of endothelial cells, which are underlaid by a discontinuous basement membrane and adventitial cells. Within the interstitium lie clusters of hematopoietic cells and fat cells. Differentiated blood cells enter the circulation by transcellular migration through the endothelial cells.
The normal marrow is organized in subtle, but important, ways. For example, normal megakaryocytes lie next to sinusoids and extend cytoplasmic processes that bud off into the bloodstream to produce platelets, while red cell precursors often surround macrophages (so-called nurse cells) that provide some of the iron needed for the synthesis of hemoglobin. Diseases that distort the marrow architecture, such as deposits of metastatic cancer or granulomatous disease, can cause the abnormal release of immature precursors into the peripheral blood, a finding that is referred to as leukoerythroblastosis
The bone marrow is a unique microenvironment that supports the orderly proliferation, differentiation, and release of blood cells. It is filled with a network of thin-walled sinusoids lined by a single layer of endothelial cells, which are underlaid by a discontinuous basement membrane and adventitial cells. Within the interstitium lie clusters of hematopoietic cells and fat cells. Differentiated blood cells enter the circulation by transcellular migration through the endothelial cells.
The normal marrow is organized in subtle, but important, ways. For example, normal megakaryocytes lie next to sinusoids and extend cytoplasmic processes that bud off into the bloodstream to produce platelets, while red cell precursors often surround macrophages (so-called nurse cells) that provide some of the iron needed for the synthesis of hemoglobin. Diseases that distort the marrow architecture, such as deposits of metastatic cancer or granulomatous disease, can cause the abnormal release of immature precursors into the peripheral blood, a finding that is referred to as leukoerythroblastosis.
Extreme reduction / complete disappearance of granulocytes in the blood.
Antibodies form against drug or its metabolite by its combination with a protein on the surface of neutrophils. (Hapten + Granulocyte Protein)=Neoantigen
Resulting in stimulation of immune system with antibody production.