challenges in interpreting abnormal hemoglobin study- the key is to correlate with patient age, ethnicity,RBC indices & morphology findings. Two tier approach for correct characterization of abnormal hemoglobins of HPLC &/or capillary electrophoresis.
This presentation is focused on diagnostic utility of Red blood cell indices which will be very useful for undergraduate and postgraduate of medical field.
challenges in interpreting abnormal hemoglobin study- the key is to correlate with patient age, ethnicity,RBC indices & morphology findings. Two tier approach for correct characterization of abnormal hemoglobins of HPLC &/or capillary electrophoresis.
This presentation is focused on diagnostic utility of Red blood cell indices which will be very useful for undergraduate and postgraduate of medical field.
The cells of the immune system arise from a pluripotent Hematopoietic Stem Cells (HSCs) through a process known as haematopoiesis.
Hematopoiesis involves the production, development, differentiation, and maturation of the blood cells (erythrocytes, megakaryocytes and leukocytes) from HSCs.
Differentiation of the HSC will occur along one of two pathways, giving rise to either a common myeloid progenitor or a common lymphoid progenitor cells in the presence of specific cytokines or soluble mediates (growth factor).
Immunology is the study of the immune system and is a very important branch of the medical and biological sciences. The immune system protects us from infection through
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.
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
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.
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
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.
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
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.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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
2. Leukocyte Disorders
• Leukocytes constitute the cellular components of the innate and
adaptive immune system and are critical for host defense. These
cells mediate acute and chronic inflammation, modulate immune
responses, and protect the host against numerous pathogens.
• Disorders affecting leukocytes can be divided broadly into
malignant disorders (tumors of leukocytes or their progenitors) and
non-malignant disorders.
• The malignant disorders are uncommon but clinically important
entities
• Non- malignant leukocyte disorders can involve any any of the
leukocytes (neutrophils, eosinophils, basophils, monocytes, B cells,
T cells, and natural killer cells)
• but the disorders of greatest clinical relevance affect neutrophils;
these will be our major focus.
4. WHAT HAPPENS IN BONE MARROW?
• Neutrophils, red cells and megakaryocytes all descended
from common precursor cell called myeloid stem cell
• Stem cells differentiate into primitive cells called blasts,
which are precursors of each cell type
• Blasts divide and mature under the influence of proteins
called growth factors; as they mature they lose the ability to
divide
• Mature neutrophils and red cells enter the blood
• Megakaryocytes break into small fragments (platelets),
which enter blood
6. Granules in Neutrophils: Primary granules: promyelocyte stage , Secondary granules: myelocyte stage and predominate therafter
Myelopoiesis
Myelopoiesis: As granulocytes develop and mature, they go through
a series of recognizable morphologic stages that correlate with the
expression of genes that confer the specific functions indicated on
the time line.
HSC, hematopoietic stem cell; PMN, polymorphonuclear leukocyte.
Life span of neutrophil in Blood is 6-10 hours
13. Polymorphonuclear Leukocytes
• Polymorphonuclear leukocytes, also called
granulocytes because their cytoplasm contains
granules, include
– Neutrophils
– Eosinophils
– Basophils
• Polymorphonuclear leukocytes occur in the
circulation and have multilobed nuclei.
15. Neutrophils
• Neutrophils constitute 40 to 70% of total circulating WBCs;
they are a first line of defense against infection. Mature
neutrophils have a half-life of about 2 to 3 days.
• During acute inflammatory responses (eg, to infection),
neutrophils, drawn by chemotactic factors and alerted by the
expression of adhesion molecules on blood vessel
endothelium, leave the circulation and enter tissues.
• Their purpose is to phagocytose and digest pathogens.
• Microorganisms are killed when phagocytosis generates lytic
enzymes and reactive oxygen compounds and triggers release
of granule contents.
16. Eosinophils
• Eosinophils are granulocytes derived from the same
progenitor cells as monocytes-macrophages,
neutrophils, and basophils. They are a component of
the innate immune system. Eosinophils have a
variety of functions, including
– Defense against parasitic infections
– Defense against intracellular bacteria
– Modulation of immediate hypersensitivity reactions
17. Eosinophils
• Eosinophils constitute up to 5% of circulating WBCs.
• They target organisms too large to be engulfed; they
kill by secreting toxic substances (eg, reactive oxygen
compounds similar to those produced in neutrophils),
major basic protein (which is toxic to parasites),
eosinophil cationic protein, and several enzymes.
• Eosinophils are also a major source of inflammatory
mediators (eg, prostaglandins, leukotrienes, platelet-
activating factor, many cytokines).
18. Eosinophil production and function
• Eosinophil production appears to be regulated by
T-Cells through the secretion of the hematopoietic
growth factors:
– granulocyte-macrophage colony-stimulating factor (GM-
CSF),
– interleukin-3 (IL-3), interleukin-5 (IL-5).
– Although GM-CSF and IL-3 also increase the production of
other myeloid cells, IL-5 increases eosinophil production
exclusively.
19. Eosinophil production and function
• Eosinophil granules contain major basic protein and
eosinophil cationic protein;
– toxic to several parasites and to mammalian cells.
– These proteins bind heparin and neutralize its anticoagulant
activity.
• Eosinophil-derived neurotoxin can severely damage
myelinated neurons.
• Eosinophil peroxidase, generates oxidizing radicals in
the presence of hydrogen peroxide and a halide.
– Charcot-Leyden crystals are primarily composed of
phospholipase B and are located in sputum, tissues, and stool
in disorders in which there is eosinophilia
(eg, asthma, eosinophilic pneumonia).
20. Normal peripheral blood
eosinophil count
• Diurnal levels vary inversely with plasma cortisol levels;
the peak occurs at night and the trough in the morning.
• The eosinophil count can decrease with stress, with the
use of beta-blockers or corticosteroids, and sometimes
during bacterial or viral infections.
• The count can increase (eosinophilia) in allergic
disorders, during certain infections (typically parasitic),
and as a result of numerous other causes.
• The circulating half-life of eosinophils is 6 to 12 h, with
most eosinophils residing in tissues (eg, the upper
respiratory tract, GI tract, skin, uterus).
21. Normal peripheral blood
eosinophil count
• Generally accepted that a count > 500/mcL is
elevated.
• Peripheral eosinophilia is characterized as
– Mild: 500 to 1500/mcL
– Moderate: 1500 to 5000/mcL
– Severe: > 5000/mcL
22. Basophils
• Basophils constitute < 5% of circulating WBCs and
share several characteristics with mast cells
• Both have high-affinity receptors for IgE called Fc-
epsilon RI (FcεRI).
• When these cells encounter certain antigens, the
bivalent IgE molecules bound to the receptors become
cross-linked, triggering cell degranulation with release
of preformed inflammatory mediators (eg, histamine,
platelet-activating factor) and generation of newly
synthesized mediators (eg, leukotrienes,
prostaglandins, thromboxanes).
23. Monocytes
• Monocytes in the circulation are precursors to tissue
macrophages.
• Monocytes migrate into tissues, where over about 8 h,
they develop into macrophages under the influence of
macrophage colony-stimulating factor (M-CSF),
secreted by various cell types (eg, endothelial cells,
fibroblasts).
• At infection sites, activated T cells secrete cytokines
(eg, interferon-gamma [IFN-gamma]) that induce
production of macrophage migration inhibitory factor,
preventing macrophages from leaving.
24. Macrophages
• Macrophages are activated by IFN-gamma and
granulocyte-macrophage colony-stimulating factor
(GM-CSF).
• Activated macrophages kill intracellular organisms and
secrete IL-1 and tumor necrosis factor-alpha (TNF-
alpha).
• These cytokines potentiate the secretion of IFN-gamma
and GM-CSF and increase the expression of adhesion
molecules on endothelial cells, facilitating leukocyte
influx and destruction of pathogens.
• Based on different gene expression profiles, subtypes
of macrophages (eg, M1, M2) have been identified.
25. Lymphocytes
• The 2 main types of lymphocytes are
– B cells (which mature in bone marrow)
– T cells (which mature in the thymus)
• They are morphologically indistinguishable but have
different immune functions.
• They can be distinguished by antigen-specific surface
receptors and molecules called clusters of
differentiation (CDs), whose presence and absence
define some subsets.
• More than 300 CDs have been identified
• Each lymphocyte recognizes a specific antigen via
surface receptors.
26. B cells
• About 5 to 15% of lymphocytes in the blood are B
cells; they are also present in the bone marrow,
spleen, lymph nodes, and mucosa-associated
lymphoid tissues.
• B cells can present antigen to T cells and release
cytokines, but their primary function is to
develop into plasma cells, which manufacture
and secrete antibodies.
• Patients with B-cell immunodeficiencies (eg, X-
linked agammaglobulinemia) are especially
susceptible to recurrent bacterial infections.
27. T cells
• T cells develop from bone marrow stem cells
that travel to the thymus, where they go
through rigorous selection. There are 3 main
types of T cell:
• Helper
• Regulatory (suppressor)
• Cytotoxic
28. Helper T (Th) cells
• Helper T (Th) cells are usually CD4 but may be CD8. They
differentiate from Th0 cells into one of the following:
• Th1 cells: In general, Th1 cells promote cell-mediated
immunity via cytotoxic T cells and macrophages and are
thus particularly involved in defense against intracellular
pathogens (eg, viruses). They can also promote the
production of some antibody classes.
• Th2 cells: Th2 cells are particularly adept at promoting
antibody production by B cells (humoral immunity) and
thus are particularly involved in directing responses aimed
at extracellular pathogens (eg, bacteria, parasites).
• Th17 cells: Th17 cells promote tissue inflammation.
29. Regulatory (suppressor) T cells
• Regulatory (suppressor) T cells mediate suppression of
immune responses and usually express the Foxp3
transcription factor.
• The process involves functional subsets of CD4 or CD8
T cells that either secrete cytokines with
immunosuppressive properties or suppress the
immune response by poorly defined mechanisms that
require cell-to-cell contact.
• Patients with functional mutations in Foxp3 develop
the autoimmune disorder IPEX
syndrome (immunodysregulation, polyendocrinopathy,
enteropathy, X-linked syndrome).
30. Cytotoxic T (Tc) cells
• Cytotoxic T (Tc) cells are usually CD8 but may be CD4; they
are vital for eliminating intracellular pathogens, especially
viruses. Tc cells play a role in organ transplant rejection.
• Tc-cell development involves 3 phases:
• A precursor cell that, when appropriately stimulated, can
differentiate into a Tc cell
• An effector cell that has differentiated and can kill its
appropriate target
• A memory cell that is quiescent (no longer stimulated) but
is ready to become an effector when restimulated by the
original antigen-MHC combination
• Fully activated Tc cells, like NK cells, can kill an infected
target cell by inducing apoptosis.
31. Mast Cells
• Mast cells are tissue-based and functionally similar to
basophils circulating in the blood.
• Mucosal mast cell granules contain tryptase and
chondroitin sulfate; connective tissue mast cell
granules contain tryptase, chymase, and heparin. By
releasing these mediators, mast cells play a key role in
generating protective acute inflammatory responses;
basophils and mast cells are the source of type I
hypersensitivity reactions associated with atopic
allergy. Degranulation can be triggered by cross-linking
of IgE receptors or by the anaphylatoxin complement
fragments C3a and C5a.
32. Definitions White Cell Numbers
• Leukocytosis: increase in the numbers of circulating white
cells: >12,000/uL
• Leukopenia: decrease in the numbers of circulating white
cells: < 4,000/uL
• Left Shift – increased circulating numbers of immature
neutrophils
• Leukoerythroblastic Reaction – leukocytosis with a left
shift accompanied by nucleated red cells: seen in
malignancy.
• Leukemoid Reaction – benign excessive leukocytosis
accompanied by an exaggerated neutrophilia and a left
shift in response to an infection; the WBC > 50 x 109/L
33. Definitions White Cell Numbers
• Neutrophilia >7.5 x 109/L
• Other defining features:
– Left shift – Increased band forms
– “toxic” cell appearance
• Dohle bodies
• Vacuoles
• Intra-cellular microbes
40. Infectious Mononucleosis
• Acute, self-limiting, febrile infection of B-cells
• Circulating reactive lymphocytes are primary CD8 T-cells
• Typically occurs in those age 10-25 years
– Fever
– Sore throat
– Lymphadenopathy
– Lethargy
Positive serology
Heterophile antibodies
41. Leukopenia
• is a reduction in the circulating WBC count to < 4000/μL. It is usually
characterized by a reduced number of circulating neutrophils, although a
reduced number of lymphocytes, monocytes, eosinophils, or basophils
may also contribute. Thus, immune function can be generally decreased.
• Neutropenia is a reduction in blood neutrophil count to < 1500/μL in
whites and < 1200/μL in blacks. It is sometimes accompanied by
monocytopenia and lymphocytopenia, which cause additional immune
deficits.
• Lymphocytopenia, in which the total number of lymphocytes is < 1000/μL
in adults, is not always recognized as a decrease in the total WBC count
because lymphocytes account for only 20 to 40% of the total WBC count.
The consequences of the lymphopenia can depend on the lymphocyte
subpopulation(s) that are decreased.
• Monocytopenia is a reduction in blood monocyte count to < 500/μL.
Monocytes migrate into the tissues where they become macrophages,
with specific characteristics depending on their tissue localization.
42. Neutropenia
Neutropenia < 1.5 x 109/L
Definition: less than the normal absolute count; greatly
influenced by patient age and race. African and Middle Eastern
populations Subclasses include mild, moderate and severe:
• Reactions to Drugs
• BM ablative therapy
• Infections
• HIV/Hepatitis
• Typhoid/ miliary TB
• Malaria
• Immune Disorders
• Systemic lupus erythromatous (SLE)
• Neoplasm
• BM Failure
• Megaloblastic Anemia
• Aplastic Anemia
• Hypersplenism
• Idiopathic (of unknown cause).
Causes
43. Neutropenia
• Neutropenia is absolute neutrophil count (ANC)
<1500 cells/microL
• Severe neutropenia is ANC <500/µL, or an ANC
that is expected to decrease to <500/µL over the
next 48 hours
ANC= WBC x (PMN % + Bands %)
Aşkın K. KAPLAN M.D.
44. Eosinopenia
• Eosinopenia is a form of agranulocytosis where the
number of eosinophil granulocytes in perepheral
blood is lower than expected < 40/cmm
– Bacterial infection
– By stress reactions
– Cushing's syndrome
– By the use of steroids
– Pathological causes include burns and acuteinfections.
45. Neutropenic Fever
• The Infectious Diseases Society of America
defines neutropenic fever as
– a single oral temperature of >38.3°C (101°F) or
– a temperature of >38.0°C (100.4°F) sustained for
>1 hour
Aşkın K. KAPLAN M.D.
46. Neutropenia Causes
• Defects inside or outside the Bone Marrow
– Decreased proliferation [failure of cells - aplasia]
– Decreased maturation [insufficient number of
precursors undergoing abnormal maturation]
– Decreased survival [increased destruction and/or
rapid removal of cells]
– Distribution [total body pools are normal,
circulating numbers are reduced]
47. Lymphopenia
• Lymphopenia Absolute lymphocyte count <0.6
x 109/L
• There are three types of abnormalities:
– Decreased production
– Increased destruction
– Changes in distribution
49. Monocytopenia
• is a reduction in blood monocyte count
to < 500/μL. Risk of certain infections is
increased. It is diagnosed by CBC with
differential. Treatment with hematopoietic
stem cell transplantation may be needed.
53. Pelger Huet vs band neutrophil
•Pelger Huet – an inherited condition
resulting in hyposegmentation of
granulocyte nuclei with increased density
and coarseness of the chromatin.. Don’t
confuse this anomaly with a neutrophilic
left shift!
•May-Hegglin - a rare syndrome
characterized by leukopenia, variable
thrombocytopenia, GIANT PLATELETS, and
gray-blue cytoplasmic inclusions in the
neutrophils and monocytes [dohle-like
bodies]
54. Alder-Reilly vs Chediak-Higashi
• Alder-Reilly - an inherited trait characterized
by the presence of abnormally large
azurophilic and basophilic granules
resembling neutrophilic toxic granulation.
• Chediak-Higashi - is a genetic disorder that
has an equivalent syndrome in mink, cattle,
mice, cats, & killer whales. Affected
individuals display partial albinism, are very
susceptible to common infectious agents, and
have white cells demonstrating giant
cytoplasmic granules.
55. Definitions
• Gaucher & Niemann-Pick are characterized by the lack of or
defective activity of enzymes.
• In Gaucher disease, there is a lack of beta-glucocerebrosidase
and macrophages become laden with glucocerebrosides.
• In Niemann-Pick, there is deficient activity of lysosomal
hydrolase and sphingomyelinase resulting in the accumulation
of cholesterol and sphingomyelin in mononuclear phagocytes.
• Mucopolysaccharidoses are a group of genetically determined
deficiencies of specific enzymes involved in the degradation of
mucopolysaccharides. Examples: Hurlers, Hunter, Sanfilippo
56. Pelger-Huet & Hypersegmentation
Bilobed and occasional
unsegmented neutrophils
Autosomal recessive disorder
Rare autosomal dominant condition
Neutrophil function is essentially normal
Pelger-Huet anomaly Neutrophil hyper-segmentation
57. May Hegglin
Neutrophils contain basophilic inclusions of RNA
Occasionally there is associated leucopenia, Thrombocytopenia
and giant platelet are frequent.
59. Chediak Higashi
Autosomal recessive disorder
Giant granules in granulocytes, monocytes and lymphocytes
Partial occulocutaneous albinism, Depressed migration and degranulation ,
Recurrent pyogenic infections , Lymphoproliferative syndrome may develop
Treatment is BMT
BMT Bone Marrow Transplant
62. Dohle Bodies and Necrobiosis
Necrobiotic WBC displays nuclear
degradation or karyorrhexis. Indicates
cell death in chemotherapy or a poorly
preserved specimen.
Single or multiple blue cytoplasmic
inclusions. They represent remnants of
rough endoplasmic reticulum from earlier
maturational stages.
They are associated with myeloid "left
shifts" and are seen in conjunction with
toxic granulation.
69. LEUKOCYTE DISORDERS
• Changes in leukocyte count and morphology often
reflect disease processes and toxic challenge.
• The type of cell affected depends upon its primary
function:
– In bacterial infections, neutrophils are most commonly
affected
– In viral infections, lymphocytes are most commonly
affected
– In parasitic infections, eosinophils are most commonly
affected.
76. The peripheral neutrophil count depends upon
Bone marrow production and release
The rate of neutrophil movement into the tissues
The proportion of circulating to marginating neutrophils
Destruction or loss of neutrophils
Neutrophil disorders
77. Physiological – may occur without tissue damage or other pathologic
stimulus.
Results from a simple redistribution of cells from the marginal pool to
the circulating pool
May occur after violent exercise, epinephrine administration,
anesthesia, or anxiety
Is also called shift neutrophilia
Neutrophilia
78. • Pathological neutrophilia are:
– Bacterial infections (most common cause)
» This usually causes an absolute neutrophilia (10-19 x109/L)
» In severe infections, the bone marrow stores may be depleted
and this can result in neutropenia (typically seen in typhoid
fever and brucellosis)
– Tissue destruction or drug intoxication (tissue infarctions, burns,
neoplasms, uremia, gout)
Neutrophilia
79. Leukemoid reaction – this is an extreme neutrophilia with a WBC
count > 30 x 109/L
Many bands, metamyelocytes, and myelocytes are seen
Occasional promyelocytes and myeloblasts may be seen.
This condition resembles a chronic myelocytic leukemia (CML), but can
be differentiated from CML based on the fact that in leukemoid
reactions:
There is no Philadelphia chromosome
The condition is transient
There is an increased leukocyte alkaline phosphatase score (more on
this later)
Leukemoid reactions may be seen in tuberculosis, chronic infections,
malignant tumors, etc.
Neutrophilia
82. Neutropenia – this may result from
Decreased bone marrow production
The bone marrow will show myeloid hypoplasia with a decreased
M:E ratio
The bone marrow storage pool, and peripheral and marginating
pools are all decreased
Immature cells may be thrown into the peripheral blood and
those younger than bands are ineffective at phagocytosis. This
can lead to overwhelming infections.
This may be due to stem cell failure, radiotherapy, chemotherapy,
or myelopthesis.
Ineffective bone marrow production
The bone marrow will be hyperplastic
Defective production is seen in megaloblastic anemias and
myelodysplasic syndromes where the abnormal cells are
destroyed before they are released from the bone marrow
Neutropenia
83. Increased cell loss
Early in an infection there is a transient decrease due to
increased movement of cells into the tissues
Could be due to an immune mechanism such as production of
anti-leukocyte antibodies
Hypersplenism
Pseudoneutropenia – alterations may occur in the circulating
to marginating pools. This may be seen in:
Viral infections
Bacterial infections with endotoxin production
Hypersensitivity reactions
Neutropenia
84. Eosinophilia may be found in
Parasitic infections
Allergic conditions and hypersensitivity reactions
Eosinophils have low affinity IgE Fc receptors and may be
important in modulating immediate hypersensitivity reactions
Cancer
Chronic inflammatory states
Eosinophil disorders
87. Lipid storage diseases – the cells are unable to
completely digest phagocytosed material
Gaucher’s disease – is a recessive autosomal disorder with a
deficiency of glucocerebroside
There is an accumulation of lipid in macrophages in lymphoid tissue
This leads to liver and spleen enlargement and destructive bone
marrow lesions
Death occurs early in life
Macrophage disorders
88. Acquired, quantitative
Is usually a self-limited reactive process to infection or inflammation
Both B and T cells are affected
Function is normal, though the morphological process may be
heterogenous
With intense proliferation, may have lymphadenopathy or
splenomegaly
Lymphocyte disorders
89. Lymphocytosis – may be relative (secondary to neutropenia) or
absolute (usually seen in viral infections); if absolute it may or may not
be accompanied by a leukocytosis
Infectious mononucleosis (IM) –
This is caused by Epstein-Barr virus infecting B lymphocytes.
The infected B cells may eventually be killed by cytotoxic T cells,
though some will continue to harbor the virus in a latent infection.
The reactive lymphocytes seen in the peripheral smear are cytotoxic
T cells
The lymphocytosis is accompanied by a leukocytosis
Lymphocyte disorders- Lymphocytosis
91. Cytomegalovirus infection
Leukocytosis with absolute lymphocytosis
Infectious lymphocytosis
Unknown etiology
Leukocytosis with absolute lymphocytosis
60-97% normal appearing lymphocytes
The increased lymphocytes are mainly T lymphs
Bordetella pertussis infection
Leukocytosis with an absolute lymphocytosis
Due to a redistribution of T lymphocytes from the tissues to the
circulation
Lymphocytes are small, normal appearing lymphocytes
Lymphocytosis
93. Lymphocytic leukemoid reaction –
Peripheral smear shows increased lymphocytes with
younger lymphocytes being seen
Can occur with tuberculosis, chickenpox and the viral
diseases discussed above
Lymphocytosis
94. Plasmocytosis
Plasma cells are rarely seen in the peripheral blood, but
they may be found under conditions of intense immune
stimulation
Lymphocytosis
95. Lymphocytopenia – caused by stress, drugs, irradiation,
and some diseases
Lymphocytopenia