test 1 info ( lectures 1-5) Flashcards
neutrophil myeloblast
0-2% in BM
15-20µm
7:1- 5:1
no granules
no aggregation of material
1-3 nucleoli
Promyelocyte
1-4% in BM
12-24 µm
5:1- 3:1
primary granules slight aggregation of nucleus larger 1-2 nucleoli more basophilic
myelocyte
5-20% in BM
1–18µm
2:1- 1:1
secondary granules
may have some primary granules
may or may not have nucleoli
last stage to divide
Metamyelocyte
5-15% in BM
10-18µm
1:1
indented kidney bean nucleus
basophilic chromatin
Band
10-35% in BM
10-16µm
1 : 1 - 1: 2
elongated nucleus ( horseshoe, S or U shaped) uniform thickness
basophilic chromatin
no filaments
Segmented
5-15% in BM
10-16µm
1:3
2-5 distinct nuclear lobes connected by strands of chromatin/ filaments
tissue neutrophils
located in Bone marrow
not phagocytic
immobile end stage cells
increased in CML, myelocytic/monocytic leukemia & myelofibrosis
features:
- Ample cytoplasm that is light blue with fine lattice structure
- blunt pseudopods
- long cytoplasmic extensions that wrap around other cells
- nucleoli are usually conspicuous
Neutrophils (bands)
2-6% of WBCs
uniform nucleus
pink cytoplasm
fine violet/pink granules
released in response to infection
neutrophils ( segmented)
50-70% of WBCs
2-5 nuclear lobes
pink cytoplasm
fine violet/pink granules
found in BM, circulating pool, marginal pool & the tissues
life span once released from BM is 10-14 days
neutrophilia: >6.0 x10^9/L
neutropenia: <1.5 x10^9/L
Monocytes
2-9% of WBCs
- largest WBC
- macrophage in tissues
- increased in inflammation: syphilis, tuberculosis, endocarditis, rheumatoid arthritis & celiac disease
features:
- gray-blue cytoplasm
- fine reddish-purple evenly distributed granules
- “ ground glass appearance”
- lacy delicate chromatin
- variation in nuclear shapes
- vacuoles may be present
- blunt pseudopods
- monocytosis count: >1.0 x10^9/L
Lymphocytes
20-44% of WBCs
increased in viral infections, batcerial infections, drug reactions, allergic reactoins, alloimmune reactions, & hyperthyroidism
features:
- smal round nucleus
- clumped chromatin
- small amount of sky- blue cytoplasm
- can have azurophilic granules
lymphocytosis:
absolute lymph count in adults: >4.0 x 20 ^ 9/L
absolute lymoh count in infants/children: >10.0 x 10 ^9/L
Lymphoblast ( L1, L2, L3)
L1
- small
- chromatin homogenous
- regular nuclear shape
- no visible nuclei
- scanty cytoplasm
L2
- large
- nucleus is irregular with clefting & indentation
- 1 or more large nucleoli
- lots of cytoplasm
L3
- large
- finely stippled
- regular nuclear shape
- 1 or more prominent nucleoli
- lots of strongly basophilic cytoplasm
- prominent cytoplasmic vacuolization
Reactive Lymph
- lymphocytes reacting towards an antigen
- increased in viral infections, bacterial infections, drug reactions & miscellaneous causes
features:
- elongated
- cytoplasm scallops around the RBCs
- peripheral basophilia
Necrobiotic WBC
- part of the normal physiological death of the cell
- can be caused by tumors or basophilia
- also seen in old patient samples
- ” chocolate chip cookie”
Megakaryocytes
largest of the hematopoietic cells in the bone marrow
30-100µm
features:
- multilobulated nucleus
- coarse linear chromatin
- bluish cytoplasm
- small dense reddish - blue granules that fragment to form plts
Eosinophils
0-4% of WBCs
- in the BM for 4 days, blood for 3-4 hrs & tissue for 8-12 days
- motile
- phagocytic
- contains enzymes that neutralize substances produced in hypersensitivity reactions ( secret proteins)
- increased in allergic reactions & parasitic infections
features:
- size of a neutrophil
- banded or bi-lobed
- pink cytoplasm
- orange/red granules
eosinophilia: >0.6 x10^9/L
Basophils
0-2% of WBCs
- contains heparin & histamine which is released during allergic reactions
- regulates inflammation
- can bind IgE antibody with antigen
- increases in CML, allergies, hypersensitivity reactions & inflammatory reactions
features:
- coarse blue-black granules that obscure the nucleus
- usually bi-lobed
basophilia: >0.2 x 10^9/ L
Plasma cells
-B lymphocytes that secretes antibodies
features:
- dark eccentric nucleus with wheel spoke pattern
- no nucleoli
- abundant deep blue cytoplasm
- clear area perinuclear zone next to the nucleus
- can have grape like vacuoles & crystalline structures
Russel Bodies
immune globulins manufactured by plasmacytes
- causes grape-like vacuoles in plasm a cells cytoplasm
appear as round globules that can be red/pink, blue or colorless
toxic granulation
- fine to coarse increased basophilic granules in the cytoplasm of neutrophils in severe infections
- dark purple to purplish black granules
- normal granules are few to none
toxic vacuolization
small to medium- sized vacuoles in neutrophils with severe infections & toxemias
Dohle bodies
- pale blue inclusions at the periphery of cytoplasm of neutrophils
- common with burns, infections, trauma, neoplasms & pregnancy
Auer rods
- reddish rod-shaped bodies or needles
- alignment of primary granules found in the cytoplasm of a myeloblast or monoblast
- shows that type of leukemia is myeloid instead of lymphoid
Faggot cells
- cells found in M3 ( acute promyelocytic leukaemia)
- there is multiple auer rods in the cytoplasm which gives the appearance of a stack or bundle of sticks/rods
Barr body
- a “drumstick” appendage made up of oval mass of dense chromatin attached to nuclear lobe by a single filament in neutrophils ( most common), eosinophils, or basophil
- normal in females
- incidence: 0.6-8.8%
Smudge cells
- broken up cells that are smeared
- usually associated with CML
- most commonly a lymph
- can be done by making smears as they are delicate
Pelger-Huet Anomaly
- qualitative disorder
- generally benign
- rare autosomal, dominant inherited abnormality of the nuclei & chromatin
- chromatin is coarse & condensed
- nucleus of neutrophil is dumbell/barbell shaped ( bilobed or not at all )
- 70-90% of neutrophils are affected
- hyposegmentation
Hypersegmentation
- larger than normal neutrophils with more than 5 lobes
- can be due to megaloblastic anemias (B12 or folate deficiency) or hereditary hypersegmentation ( benign autosomal dominant disorder)
Chediak- Higashi syndrome
- rare autosomal recessive condition with azurophilic granulation of all leukocytes
- abnormal granulation is characteristic of defective chemotaxis
- moderate neutropenia & thrombopenia
- patient has partial or complete albinism
features:
- large green primary granules
- large reddish- purple secondary granules
Alders Anomaly
- rare genetic disorder with dark staining coarse granules in granulocytes, monocytes & sometimes lymphocytes
- inherited autosomal- recessive disorder pf mucopolysaccharidosis
- associated with mucopolysachharidosis, Hunter’s & Hurler’s syndrome
- granules are produced by precipitated mucopolysaccharides
May- Hegglin Anomaly
- Congenital autosomal dominant disorder associated with decreased platelet production ( thrombocytopenia), giant platelets & variable neutropenia
- granulocytes & monocytes have blue-staining cytoplasmic inclusions that resemble dohle bodies, except they are larger
- granules may also be found in eosinophils & basophils
Infectious Mononucleosis Pathophysiology
- caused by Epstein- barr Virus
- EBV is herpesvirus also known as human herpesvirus4
- EBV is the most common cause of mono
- there is an overactive immune system in patients with infectious mononucleosis
infectious mononucleosis transmission
- spread orally “ kissing disease”
- when B cells & epithelial cells of the oropharynx are infected with EBV it causes the virus to shed in the saliva
- infection of these cells makes it east for the virus to spread through bood to other B cells & lymphatic tissue
- EBV binds to the CD21 receptors on B lymphocytes & some epithelial cells in the oropharynx
infectious mononucleosis ( affected)
high incidence of active disease in late teens - early 20s
infectious mononucleosis symptoms
- individuals may be asymptomatic for several weeks
- incubation period is 3-6 weeks from infection with EBV to binding of the B cells & onset of symptoms
- malaise, headache, fever, sore throat, swollen lymph nodes, fatigue, splenomegaly ( in 50% of cases), hepatomegaly & decreased appetite due to spleen compressing the stomach
- can have tonsilitis ( can be enlarged with whiteish- greyish exudate on the tonsils; airway obstruction is possible)
- Leukoplakia; white patches on the sides of tongue
- early satiety: full before meal is done
- self limiting & usually resolves in 2-4 weeks
- may get autoimmune hemolytic anemia due to antobodies against “i” RBC antigen
Infectious mononucleosis diagnosis
- serology testing
- used to detect the presence of heterophiles Abs
- they are antibodies produced by B cells against the EBV
- “monospot”
- note: patient may not have the antibody the first time tested but if still symptomatic & tested again can show antibody ( needs time to develop) - throat swab
- for differential diagnosis to see if the patient has strep throat - CBC with differential
- lymphocytosis, possibly 10-20 x10 ^ 9/L
- reactive lymphocytes
- 1st week may see neutrophilia. later 50-80% mononuclear cells - virology
- further investigation could include a special test for the specific EBV antibody panel
- this is usually not needed
infectious mononucleosis may be confused with
- clinical presentation can be confused with strept throat
- some patient with mono develop a rash when exposed to any antibiotic in the penicillin family
- these patients will not respond to antibodies if given for treatment
infectious mononucleosis treatment
- rest
- ibuprofen
- fluids/nutrition
- if airway is obstructed may need steroids to reduce the swelling
- may need tonsillectomy
- no contact sports for 3-4 weeks as there is a concern the spleen could rupture
Chronic Myeloproliferative disorders
- a group of malignant disorders characterized by excessive proliferation of hematopoietic cells in the bone marrow
- Chronic Myeloproliferative Disorders: A group of heterogenous diseases that came from the expansion of the hematopoietic pluripotent stem cell resulting in overproduction of one or more of the formed elements of the blood
- the hallmark physical finding of CMPDs is splenomegaly which occurs in 40-99% of patients depending on disorder
- CML( chronic myelogenous leukemia) ; excessive production of granulocytes
- PV(polycythemia vera) ; overproduction of RBCs
- ET(essential thrombocythemia) ; overproduction of platelets
- IMF( idopathic myelofibrosis) ; prominence of marrow fibrosis & extramedularry hematopoiesis in the liver & spleen
Erythrocytosis
increase in the circulating RBCs producing an HCT more than 52% in males & 47% in females
- an elevated HCT is present in 2 major conditions : relative erythrocytosis & absolute erythrocytosis
relative erythrocytosis
a decrease in the total blood volume with normal RBC levels but decreased plasma volume
- RBCs are not increased but looks that way as HCT & HB are increased, this is due to the loss of plasma which concentrates the patient sample
- usually, it can be managed by restoring the amount of plasma volume
- can be the result of an acute or chronic state
Acute plasma loss ( relative erythrocytosis)
- marked loss of fluids from burns, diarrhea or diuretic therapy
- decrease in fluid intake
- redistribution in body fluids like acute trauma
Chronic plasma loss ( relative erythrocytosis )
- usually seen in stress erythrocytosis
- presents in middle age
- associated with anxiety
- WBCs & plts are not increased
- may have physical appearance of a polcythemic
- no hepatosplenomegaly
relative erythrocytosis expected results
- Normal RBCs
- Normal EPO
- Normal WBC count
- Normal plt count
- Normal LAP score
- Normal bone marrow
- Decreased plasma volume
Absolute erythrocytosis
- Absolute red cell mass is increased
- Normal or slightly increased plasma volume
primary cause of Absolute erythrocytosis
autonomous erythropoiesis or polycythemia (rubra) vera
- PV is the primary cause
- its a disorder with increased RBC production & normal/low EPO
Secondary causes of absolute erythropoiesis
- Hypoxemia/DEcreased oxygen saturation
- increased in RBCs to compensate for the decrease in 02 - HIgh altitude
- Heavy smoking
- CArbon monoxide poisoning
- Pulmonary Disease ( COPD)
- Cardiovascular Disease
- Autonomous erythropoietin production
- tumors can cause EPO to be produced - Post kidney transplant
absolute erythropoiesis treatment
therapeutic phlebotomy
Polycythemia Vera
- also known as Polycythemia Rubra Vera
- “ ruddy” facial appearance ( ski mask formation of the face)
Polycythemia Vera Pathology
- a malignancy with excessive BM production of RBCs & an increase in the total RBC volume
- Mutation in the JAK-2-gene ( linked to ionization radiation & exposure to toxins such as benzene )
- when this occurs, there is activation of RBC production without EPO
- this leads to increased RBC volume with low/normal EPO levels
- increased HCT & HB are seen as well
- Increase in lactate dehydrogenase as it spills out of destroyed RBCs
- JAK-2 is involved with receptors for EPO, TPO, IL-3 & G-CSF
- WBC & plts may increase to a lesser degree
- increased blood viscosity
- myelobfibrosis or acute myeloid leukemia may develop
- anemia
- extramedullary hematopoiesis
- hypersplenism
Polycythemia WBCs
- increase in 80% of patients
- immature forms not seen normally
- Eosinophils & basophils can be increased
- 1/3 have high LAP score ( 70%)
polycythemia vera PLts
- normal
- thrombosis in more than half the cases
Polycythemia Vera Bone marrow
- Hypercellular/Hyperplastic
- Erythroid hyperplasia
- increased megakaryocytes & myelopoiesis
- granulocytic hyperplasia
- fibrosis
- increasued reticulin in post- polycythemic myelofibrosis & myeloid metaplasia
- iron stores are often depleted
polycythemia vera smear
- may see nucleated RBCs & poikilocytes
- N/N RBCs
- but if they cant increase iron stores to compensate for the extra RBCs than Micro/Hypo
Polycythemia Vera affected
- individuals 55-70 years old
- average age is 60
- slightly more common in males
Polycythemia Vera Symptoms
- mental confusion, headache, dizziness, visual changes, tinnitus, paresthesia, weight loss, epigastric pain , gout, pruritus ( itchy skin), thrombosis, hemorrhage, plethora, hypertension, a mild to moderate degree of splenomegaly ( 75% of cases due to increased RBCs) and hepatomegaly ( 35% of cases due to increased plts)
Polycythemia Vera Diagnosis
- look at HB & HCT levels
- Serum EPO
- low/normal = primary
- high= secondary
- genetic testing to detect the presence of JAK-2 gene
- Bone marrow findings consistent with pleomorphic megakaryocytes
Polycythemia Vera treatment
- therapeutic phlebotomy
- Acetylsalicylic acid ( ASA) to reduce thrombosis
- Hydroxcyurea to reduce RBCs
- JAK-2 inhibitors
Lipid ( Lysosomal ) storage disease
- a group of inherited autosomal recessive diseases of metabolis
- strategic metabolic enzymes are missing or deficient because of a single gene deletion
- this causes the metabolic products (the enzymes in the lysosome normally would have broken down) to build up
- Histocytes, monocytes, macrophages & the cells of the bone marrow, liver, spleen ^ lymph nodes are affected
- there are usually large easily identifiable cells specific to each disease
- these cells are usually found within the BM - there is no cure for lipid storage diseases
Gaucher’s disease
enzyme deficient: beta-glucocerebrosidase
- the most common lysosomal storage disease
- caused by a deficiency of the enzyme
- this causes buildup pf the glycolipid glucocerbroside in the lysosomes of the macrophages
- single gene deletion occurs on chromosme 1
- lipid filled Gaucher cells displace normal cells in BM, spleen, liver, lungs & CNS
Gauchers disease affects
more common in Jewish people from eastern Europe
Gaucher’s disease symptoms
- Pancytopenia
- Splenomegaly
- Hepatosplenomegaly
- bone lesions
- osteonecrosis of the femoral head
- Pulmonary issues
Gaucher’s disease Identifying cell
- called the “Gaucher cell”
- the cytoplasm has a crumpled tissue paper look
- wrinkled cytoplasm
- It’s lipid laden
Gaucher’s disease lab features
- N/N or N/Hypo anemia
- leukopenia
- thrombopenia
- increased serum acid phosphatase
- PAS reaction is positive for carbohydrates
Gaucher’s disease treatment
- enzyme replacement therapy
- Glucocerebrosidase is currently done
- helps with viseral & hematological manifestations
- skeletal disease responds more slowly
- pulmonary involvement is relatively resistant to the enzyme - surgical care
- partial & total splenectomy - Bone marrow transplant
- Gene replacement
- the permanent cure
Nieman-Pick disease
enzyme deficient : Sphingomyelinase
- caused by the deficiency of the enzyme
- this causes a build up of sphingomyelin in the macrophages/ histocytic lysosomes
- single gene deletion occurs on chromosome 11
- the phagocytic cells of the BM, spleen, liver, lymph nodes & lungs are stuffed with droplets of the complex lipid giving them a fine vacuolation of foaminess to the cytoplasm
- neurons of the CNS also become enlarged & vacuolated
3 types of Nieman -pcik disease
- type A
- manifests in infancy with massive visceromegaly & severe neurologic deterioration
- lung diseases occur as well - type B
- no neurological disorders - type C
- dementia & depression
Nieman pick disease affects
- increased prevalance in Ashkenazi Jewish population
- affects girls more often than boys
Nieman pick disease symptoms
- growth slowed or delayed
- hepatosplenomegaly
- Lymphadenopathy
- Pigmentation
- Neurological involvement/ impairment (depending on type)
- cherry-red spots in the macula of each eye ( ~1/3)
Nieman pick disease identifying cell
- called a “foam cell”
- other names “ droplet” or “lipid - laden giant foam cell”
- they are found within bone marrow, aspirate, tissues & organs
Nieman pick disease lab features
- PAS reaction id negative
Tay Sachs disease
Enzyme deficient: Hexodsaminidase A ( hex-A)
- caused by a deficiency of the enzyme
- this causes a build up of GM2 gangliosides in the brain & other tissues
- single gene deletion on chromosome 15
- nerve cells on the brain & spinal cord are destroyed
Tay Sachs disease affects
- higher incidence in the Ashkenazi Jewish population
Tay Sachs disease Symptoms
- appear 3-6 months after birth
- loss of motor control
- atrophy of muscles
- seizures
- death usually by 4 years of age
- cherry-red spot in the macula of eyes
- Neurodegeneration
- Physical & mental deterioration
- Macrocephaly
- Paralysis
- usually NO hepatosplenomegaly seen
Tay Sachs disease identifying cell
-“ onion skin” appearance to cell/lysosomes
Mucopolysaccharidoses (MPS)
- disorder that constitute a group of lysosomal storage diseases caused by a deficiency in one of the enzymes involved in the breakdown of mucopolysaccharides (MPSs)
- rare genetic disorders with most being autosomal recessive
- it causes the buildup of mucopolysaccharides or now called glucosaminoglycans ( GAG) in the lysosomes
- they are chains of carbohydrates
- products are found in the reticuloendothelial system ( spleen, BM. & liver), lymph nodes, blood vessels, brain, heart, connective tissues & urine
Mucopolysaccharidosis symptoms
- there are progressive disorders with multisystem involvement
- there is a wide spectrum of severity from mild to severe
- developmental delay
- macrocephaly with thicken skulls
- spinal cord compression
- hearing loss
- corneal clouding
- abnormal gums/teeth & enamel
- obstructive sleep apnea
- heart disease, due to storage of GAG& secondary fibrosis making valves abnormal
- joint stiffness
- dysplastic hips
- heptaosplenomegaly, most likely due to tissue accumulation of GAG
- intestinal/umbilical hernias
- skeletal disease, likley due to the distruption of groeth plates
- airway disease, secondary to storage of GAG in soft tissue causing a “floppy trachea”
- CNS issues, cause in unknown maybe due to secondary issues like inflammation
Mucopolysaccaridosis diagnosis
- initial screening includes a toludine blue spot test or turbidity test
- enzyme assays are needed to diagnose
-blood smears- see large granules in leukocytes, especially
lymphocytes - Alder-Reilly bodies
- Toludine blue stain may be used
- see large granules in leukocytes, especially
Mucopolysaccaridosis treatment
- Hematopoietic stem cell transplant (HSCT)- BM transplant
- Intravenous Enzyme Replacement Therapy (ERT)
- requires weekly transufusions
- expensive
- IV administration of enzymes doesnt allow for crossing of the blood-brain barrier so treatment for CNS involvement is impaired
- Spinal ERT
- Gene Therapy
- Blood- brain barrier penetration of proteins
Hunter’s syndrome- MPS ll
enzyme deficient: iduronate-2-sulfatase (I2S)
- X-linked recessive disorder
- female carriers usually are carriers with no evidence of the disease
- GAGs buidup in the lysosomes
- rare; 1 in 100, 000
Hunter’s syndrome symptoms
- onset between 1-3 years of age in the severe form
- a multi-system disorder that has skeletal, physical, respiratory & airway involvement
- in sever form the following CNS features are present:
- Progressive cognitive impairement
- Seizures
- Hearing loss
- Decreased night & peripheral vision loss
- note: corneal clouding is typically absent in those with hunter’s syndrome
Hurler’s Syndrome - MPS l
enzyme deficient: alpha-L- iduronidase
- rare; 1 in 100, 000
- autosomal recessive
- can range from severe to mild symptoms with the mild or attenuated form being called Scheie MPS l
Hurler’s syndrome symptoms
- onset occurs before 6 months of age in the severe form
- skeletal abnormalities
-cognitive impairment - heart disease ( myocardial infraction )
- respiratory problems
- hepatosplenomegaly
- coarse facial features “ gargoyle like”
- flatten nasal bridge, elongated skull, prominent facial
bones & widely spaced eye sockets
- flatten nasal bridge, elongated skull, prominent facial
- corneal clouding
- developmental delays, usually fine at birth & takes 3-6 months to see symptoms
- recurring UTIs
Hurler’s syndrome treatment
- bone marrow transplant
- enzyme replacement therapy
- supportive care
