Chapter 13.2--Reactive proliferations of White cells and lymph nodes Flashcards
(47 cards)
1
Q
Leukocytosis
A
- increase in the number of white cells in blood
- common reaction to inflammatory states
2
Q
Pathogenesis of leukocytosis–peripheral blood leukocyte count is influenced by several factors including:
A
- size of myeloid and lymphoid precursor and storage cell pools in bone marrow, thymus, circulation and peripheral tissues
- rate of release of cells from storage pools into circulation
- proportion of cells that are adherent to blood vessel walls at any time (marginal pool)
- rate of extravasation of cells from blood into tissues
3
Q
Leukocytosis–increased production in marrow caused by?
A
- chronic infection or inflammation (growth factor dependent)–most important!!
- paraneoplastic (Hodgkin lymphoma, growth factor dependent)
- Myeloproliferative disorders (chronic myelooid leukemia; growth factor-independent)
4
Q
Leukocytosis–increased release from marrow stores caused by?
A
- Endotoxemia
- Infection
- Hypoxia
5
Q
Leukocytosis–decreased margination caused by?
A
- exercise
- catecholamines
6
Q
Leukocytosis–decreased extravasation into tissues caused by?
A
-Glucocorticoids
7
Q
Leukocyte homeostasis is maintained by?
A
-cytokines, growth factors and adhesion molecules through their effects on the committment, proliferation, differentiation and extravasation of leukocytes and progenitors
8
Q
Acute infection
A
-rapid increase in the egress of mature granulocytes from bone marrow pool, an alteration that may be mediated through the effects of TNF and IL-1
9
Q
-if infection or inflammatory process is prolonged,
A
- IL-1, TNF and other inflammatory mediators stimulate macrophages, bone marrow stromal cells and T cells to produce increased amounts of hematopoetic growth factors which enhance the proliferation and differentiation of committed granulocytic progenitors and cause a sustained increase in neutrophil production
10
Q
IL-5 mainly stimualates? G-CSF induces?
A
- IL-5=eiosinophil production
- G-CSF=neutrophilia
11
Q
In sepsis or severe inflammatory disorders (like Kawasaki disease), leukocytosis is often accompanied by?
A
-morphologic changes in neutrophils like toxic granulations, Dohle bodies and cytoplasmic vacuoles
12
Q
Toxic granules
A
-coarser and darker than the normal neutrophilic grnaules–represent abnormal azurophilic (primary granules)
13
Q
Dohle bodies
A
-patches of dilated ER that appear as sky-blue cytoplasmic puddles
14
Q
Usually its easy to distinguish reactive vs. neoplastic leukocytosis; but when do they become uncertain?
A
- Acute viral infections, esp in children can cause the appearance of large numbers of activated lymphocytes that resemble neoplastic lymphoid cells
- At other times, esp in severe infections, many immature granulocytes appear in the blood, mimicking myeloid leukemia (leukemoid reaction)
- Special lab studies helpful in distinguishing reactive and neoplastic leukocytosis
15
Q
Types of leukocytosis
A
- Neutrophilic leukocytosis
- Eiosinophilic leukocytosis
- Basophilic leukocytosis
- Monocytosis
- Lymphocytosis
16
Q
Neutrophilic leukocytosis
A
-acute bacterial infections, esp those cuased by pyogenic orgnaisms; sterile inflammation caused by for example, tissue necrosis (myocardial infarction, burns)
17
Q
Eiosinophilic leukocytosis (eiosinophilia)
A
-allergic disorders like asthma, hay fever, parasitic infections; drug reactions; certain malignancies (Hodkin and some non-Hodgkin lymphomas); autoimmune disorders (pephigus, dermatitis herpetiformis) and some vasculitidies; atheroembolic disease (transient)
18
Q
Basophilic leukocytosis (basophilia)
A
-rare, indicative of myeloproliferative disease (chronic myelogenous leukemia)
19
Q
Monocytosis
A
-Chronic infections (TB), bacterial endocarditis, rickettsiosis, and malaria; autoimmune disorders (SLE); inflammatory bowel diseases (UC)
20
Q
Lymphocytosis
A
-accompanies monocytosis in many disorders associated with chronic immunologic stimulation (TB, brucellosis); viral infections (hep A, cytomegalovirus, EBV); Bordatella pertussis infection
21
Q
Lymphadenitis–primary lymphoid organs
A
–follow initial development from precursors in the central (primary lymphoid organs)–>bone marrow for B cells and thymus for T cells
22
Q
Secondary lymphoid organs
A
- Lymphocytes circulate in the blood and under the influence of specific cytokines and chemokines, home to lymph nodes, spleen, tonsils, adenoids and Peyer’s pathces (secondary lymphoid tissues)
- Lymph nodes are the most widely distributed and easily accessible lymphoid tissue and are frequently examined for diagnostic purposes–>are discreted encapsulated structures that contain well-organized B-cell and T-cell zones which are richly invested with phagocytes and Ag-presenting cells
23
Q
Morphologic changes associated with activation of resident immune cells
A
- within several days of Ag stimulation, primary follicles enlarge and develop pale-staining germinal centers–highly dynamic structures where B cells acquire capacity to make high-affinity Abs against Ags
- Trivial injuries/infections induce subtle changes which signficant infections produce nodal enlargement and can leave scarring so lymph nodes in adults are almost never normal or resting and need to compare nodes from past to present
- Infections and inflammatory stimule elicit regional or systemic immune reactions in lymph nodes and cause stereotypical patterns of lymph node reaction designated acute and chronic nonspecific lymphadenitis
24
Q
Acute nonspecific lymphadenitis
A
- in cervical region is due to drainage of microbes or microbial products from infection of teeth or tonsiles
- in axillary or inguinal regions is caused by infections of extremeities
- in mesenteric lymph nodes caused by draining acute appenditicitis or other self-limited infections which mimick acute appendicitis
- Systemic viral infections (esp in children) and bacteremia produce acute generalized lymphadenopathy
25
Morphology of acute nonspecific lymphadenitis
- nodes are swollen, gray-red and engorged
- prominence of large reactive germinal centers with many mitotic figures
- macrophages contain particulate debris derived from dead bacteria or necrotic cells
- when pyogenic organisms are the cause, neutrophils are prominent and the centers of the follicles may undergo necrosis--sometimes entire node becomes bag of pus
- with less severe reactions, scattered neutrophils infiltrate about the follicles and accumulate within lymphoid sinuses; the endothelial cells lining the sinueses undergo hyperplasia
26
Acute nonspecific lymphadenitis--clinical features
-Nodes are enlarged and painful; when abscess formation is extensive, nodes become fluctuant--overlying skin is red and sometimes suppurative infections penetrate through the capsule of node and track to the skin to produce draining sinuses; healing associated with scarring
27
chronic nonspecific lymphadenitis
- many different patterns
| - nontender; nodal enlargement occurs slowly and acute inflammation with associated tissue damage is absent
28
Chronic lymphadenitis is particularly common in
-ingluinal and axillary lymph nodes which drain large areas and are stimulated by immune reactions to trivial injuries and infections of the extremities
29
Tertiary lymphoid tissues
- organized collections of immune cells in nonlymphoid tissues due to chronic immune reactions
- example=chronic gastritis caused by H. pylori where aggregates of mucosal lymphocytes are seen that stimulate the appearance of Peyer patches
- also occurs in RA where B-cell follicles appear in inflammed synovium
30
Lymphotoxin
-cytokine required for formation of normal Peyer patches--involved in establishment of these "extranodal "inflammation-induced collections of lymphoid cells
31
Hemophagocytic Lymphohistiocytosis (HLH)
- reactive condition marked by cytopenias and signs and symptoms of systemic inflammation related to macrophage activation
- also refereed to as macrophage activation syndrome
- some are familial and can affect people early while others sporadic and affect people of any age
32
Pathogenesis of HLH--the common feature of all forms of HLH is??
- systemic activation of macrophages and CD8+ cytotoxic T cells
- the activated macrophages phagocytose blood cell progenitors in the marrow and formed elements in the peripheral tissues while the stew of mediators released from macrophages and lymphocytes suppress hematopoiessis and produce symptoms of systemic inflammation--this leads to cytopenias and a shock-like picture sometimes referred to as cytokine storm or the systemic inflammatory response syndrome
33
Familial forms of HLH are associated with
- several different mutations, all of which impact the ability of cytotoxic T cells and NK to properly form or deploy cytotoxic granules
- not known how these defects lead to HLH but one theory is that cytotoxic T cells keep immune responses in check by lysing Ag-bearing dendritic cells or activated macrophages; if this regulatory mechanism fails, hyperactivation of immune system and the clinical syndrome of HLH ensue
34
Unbriddled HLH is associated with
- high levels of inflammatory mediators like IFN-y, TNFa, IL-6, and IL-12 as well as soluble IL-2 receptor
- some sporadic cases in adults also prove to have mutations in the same set of genes while in other adult-onset patients the same cause is unknown
35
The most common trigger for HLH is
-infection, esp with EBV!!!
36
Clinical features of HLH
- patients present with acute febrile illness associated with splenomegaly and hepatomegaly
- Hemophagocytosis usually seen on bone marrow exam but neither sufficient or required to make Dx
- Labs show anemia, thrombocytopenia, and high levels of plasma ferritin and soluble IL-2 receptor, both indicative of severe inflammation as well as elevated liver function tests and triglyceride levels--both related to hepatitis
- Coagulation studies may show DIC--can lead to multiorgan failure, shock and death
37
Treatment of HLH
- immunosuppressive drugs and mild chemotherapy
- Pts with germline mutations that cause HLH or who have persistent/resistant disease are candidates for hematopoetic stem cell transplantation
38
HLH prognosis
-W/o tx, grim prognosis esp in those with familial forms who typically survive less than 2 months; with prompt Tx, with or without subsequent hematopoetic stem cell transplant, roughly half of pts survive though many do so with consequences like renal damage in adults and growth and mental retardation in children
39
Neoplastic proliferations of white cells--what are the most important disorders of white cells?
- Malignancies; fall into these broad categories:
- Lymphoid neoplasms
- Myeloid neoplasms
- Histiocytosis
40
Lymphoid neoplasms
- diverse group of tumors of B-cell, T-cell and NK-cell origin
- many times, the phenotype of the neoplastic cell closely resembles that of a particular stage of normal lymphocyte maturation--used in Dx and classification
41
Myeloid neoplasms
- arise from early hematopoietic progenitors
- 3 categories: acute myeloid leukemias (immature progenitor cells accumulate in bone marrow); myeloid dysplastic syndromes (associated with ineffective hematopoiesis and resultant peripheral blod cytopenias) and chronic myeloproliferative disorders (increased production of one or more terminally differentiated myeloid elements (granulocytes) leads to elevated peripheral blood counts
42
Histiocytes
- uncommon proliferative lesions of macrophages and dendritic cells
- A special type of immature dendritic cell (Langerhans cell), gives rise to a spectrum of neoplastic disorders called the Langerhans cell histiocytes
43
Morphology--chronic nonspecific lymphadenitis--follicular hyperplasia
- caused by stimuli that activate humoral immune responses
- large oblong germinal centers (secondary follicles) which are surrounded by a collar of small resting naive B cells--the mantle zone
- Germinal centers are polarized with 2 distinct regions: a dark zone with proliferating blastlike B cells (centroblasts) and a light zone made of B cells with irregular or cleaved nuclear contours (centrocytes)
- Interspersed bw the germinal B centers is an inconspicious netowork of Ag-presenting follicular dendritic cells and macrophages (tingible body macrophages!!) with nuclear debris of B cells which undergo apoptosis if they fail to produce an Ab with a high affinity for Ag
44
Causes of follicular hyperplasia inlcude
- RA, toxoplasmosis, early stages of infection with HIV
| - morphologically similar to follicular lymphoma
45
Features favoring a reactive (nonneoplastic hyperplasia) include
- preservation of lymph node architecture, including the interfollicular T-cell zones and the sinusoids
- marked variation in shape and size of follicles and
- presence of frequent mitotic figures, phagocytic macrophages and recognizable light and dark zones, all of which tend to eb absent from neoplastic follicles
46
Paracortical hyperplasia
- caused by stimuli that trigger T-cell mediated immune responses like acute viral infections (infectious mononucleosis)
- T cell regions contain immunoblasts, activated T cells 3-4x the size of resting lymphocytes that have round nuclei, open chromatin, several prominent nucleoli and moderate amounts of pale cytoplasm
- The expanded T cell zones encroach on and efface the B-cell follicles--immunoblasts may be so many that special studies needed to exclude lymphoid neoplasm
- also see hypertrophy of sinusoidal and vascular endothelial cells, sometimes accompanied by infiltrating macrophages and eiosinophils
47
Sinus histiocytosis
- also called reticular hyperplasia
- increase in number and size of cells that line lymphatic sinusoids
- prominent in lymph nodes draining cancers like carcinoma of the breast
- the lining lymphatic endothelial cells are markedly hypertrophied and macrophages are greatly increased in numbers resulting in expansion and distension of the sinuses
