1
Q
Derivation of vWF during primary hemostasis
A
- Weibel-Palade bodies of endothelial cells
- Alpha granules of platelets
2
Q
Derivation of ADP during primary hemostasis
A
Dense granules of platelets
3
Q
Cause of platelet microthrombi in HUS
A
Typically due to damage done to endothelial cells by E coli verotoxin
4
Q
Renal insufficiency - HUS or TTP?
A
More common in HUS
5
Q
CNS abnormalities - HUS or TTP?
A
More common in TTP
6
Q
Bernard-Soulier syndrome
A
- GpIb deficiency
- Platelet ADHESION is impaired
- Blood smear shows mild thrombocytopenia with enlarged platelets
7
Q
Glanzmann thrombasthenia
A
- GpIIb/IIIa deficiency
- Platelet AGGREGATION impaired
8
Q
Uremia induced qualitative platelet disorder
A
- Disrupts platelet function
- Both adhesion and aggregation are impaired
9
Q
Coagulation factor inhibitor
A
- Acquired antibody against a coagulation factor resulting in impaired factor function
- Anti-FVIII is most common
- Clinical and lab findings are similar to hemophilia A
- PTT does NOT correct upon mizing normal plasma with patient’s plasma (mixing study) due to inhibitor [PTT does correct in hemophilia A]
10
Q
Increased, decreased or normal PTT in von Willebrand disease?
A
- Increased PTT, normal PT
- Decreased FVIII half-life (vWF normally stabilizes FVIII); however, deep tissue, joint and postsurgical bleeding are usually not seen
11
Q
von Willebrand disease ristocetin test results
A
- Abnormal RISTOCETIN TEST - ristocetin induces platelet agglutination by causing vWF to bind platelet GpIb; lack o vWF leads to impaired agglutination which leads to an abnormal test
12
Q
Best screening test for DIC
A
Elevated D-dimer
13
Q
Fibrinolytic disorder - increased, decreased or normal levels D-dimer
A
- Increased fibrinogen split products without D-dimers
- Serum fibrinogen is lysed
- D-dimers are not formed because fibrin thrombi are absent
14
Q
Role of heparin-like molecules secreted by endothelial cells
A
Augment antithrombin III (ATIII) which inctivates thrombin and coagulation factors
15
Q
Role of thrombomodulin secreted by endothelial cells
A
Redirects thrombin to activate protein C, which inactivates factors V and VIII
16
Q
Causes of endothelial damage include
A
- Atherosclerosis
- Vasculitis
- High levels of homocyteine
17
Q
Causes of high levels of homocysteine
A
- Vitamin B12 and folate deficiency
- Cystathione beta synthase (CBS) deficiency
18
Q
Cystathione beta synthase (CBS) deficiency
A
- Results in high homocysteine levels with homocysteinuria
- CBS convers homocystein to cystathione
- Enzyme deficiency leads to homocysteine buildup
- Characteried by vessel thrombosis, mental retardation, lens dislocation, and longer slender fingers (these people have kyphosis and Marfanoid habitus)
19
Q
Protein C or S deficiency
A
- Hypercoagulable state
- AD
- Decreases negative feedback on the coagulation cascade
- Proteins C and S normally inactivate factors V and VIII
- Increased risk for warfarin skin necrosis
- Initial stage of warfarin therapy results in a temporary deficiency of proteins C and S (due to shorter half-life) relative to factors II, VII, IX and X
- In preexisting C or S deficiency, a severe deficiency is seen at the onset of warfarin therapy increasing the risk for thrombosis, especially in the skin
20
Q
Factor V Leiden
A
- Hypercoaguable state
- Mutated form of factor V that lacks the cleavage site for deactivation by proteins C and S
- Most common inherited cause of hypercoaguable state
21
Q
Prothrombin 20210A
A
- Hypercoaguable state
- Inherited point mutation in prothrombin that results in increased gene expression
- Increased prothrombin results in increased thrombin, promoting thrombus formation
22
Q
ATIII deficiency
A
- Hypercoaguable state
- Decreased the protective effect of heparin-like molecules produced by endothelium, increasing the risk for thrombus
- Heparin-like molecules normally activate ATIII, which inactivates thrombin and coagulation factors
- In ATIII deficiency, PTT does not rise with standard heparin dosing
- Pharmacologic heparin works by binding and activating ATIII
- High doses of heparin activate limited ATIII
- Coumadin is then given to maintain an anticoagulated state
23
Q
How do oral contraceptives cause a hypercoaguable state?
A
Estrogen enhances increased production of coagulation factors, thereby increasing the risk for thrombosis
24
Q
Caisson disease
A
- Chronic form of decompression sickness
- Characterized by multifocal ischemic necrosis of bone
25
Amniotic fluid embous
- Enters maternal circulation during labor or delivery
- Presents with shortness of breath, neurologic symptoms, and DIC (due to thrombogenic nature of amniotic fluid)
- Characterized by squamous cells and keratin debris (from fetal skin) in the embolus
26
Microcytosis is due to
An "extra" division which occurs to maintain hemoglobin concentration
27
Congenital cause of sideroblastic anemia
Most commonly involves ALA synthetase (rate-limiting enzyme that converts succinyl CoA to aminolevullinic acid (ALA) using vitamin B6 as a cofactor)
28
Acquired causes of sideroblastic anemia
- ALCOHOLISM: mitochondrial poison
- LEAD POISONING: inhibits ALA dehydratase (converts ALA to porphobilinogen) and ferrochelatase (attaches protoporphyrin to iron to make heme)
- VITAMIN B6 DEFICIENCY: required cofactor for ALA synthetase; most commonly seen as a side effect of isoniazid treatment
29
α thalassemias is usually due to gene (mutation or deletion) whereas βthalassemias is usually due to gene (mutation or deletion)
- α thalassemias → gene deletion
| - β thalassemias → gene mutation
30
Megaloblastic change is seen in which cells
- Impaired division and enlargement of RBC precursors leads to megaloblastic anemia
- impaired division of granulocyte precursors leads to hypersegmented neutrophils
- Megaloblastic change is also seen in rapidly dividing (eg intestinal) epithelial cells
31
Dietary B12 absorption
- Salivary gland enzymes (eg amylase) liberate vitamin B12, which is then bound by R-binder (also from the salivary gland) and carried through the stomach
- Pancreatic proteases in the duodenum detach vitamin B12 from R-binder
- Vitamin B12 binds intrinsic factor (made by gastric parietal cells) in the small bowel; the intrinsic factor-B12 complex is absorbed in the ileum
32
Describe subacute combined degeneration of the spinal cord
- Seen in vitamin B12 deficiency
- Increased levels of methylmalonic acid (cannot be converted to succinyl CoA, an important step of fatty acid metabolism)
- Increased levels of methylmalonic acid impair spinal cord myelinization
- Damage results in poor propioception and vibratory sensation (posterior columns) and spastic paresis (lateral corticospinal tract)
33
Examples of vaso-occlusion due to extensive sickling
- Dactylitis (common presenting sign in infants)
- Autosplenectomy (can lead to infection, most common cause of death in children)
- Acute chest syndrome (most common cause of death in adults)
- Pain crisis
- Renal papillary necrosis
34
Sickle cell trait RBCs sickle in what location
Sickle cell trait is generally asymptomatic with no anemia as RBCs with
35
Are sickle cells and target cells seen on blood smear of sickle cell trait
No
36
Metabisulfite screen
Causes cells with any amount of HbS to sickle, therefore positive in both sickle cell disease and trait
37
Describe the blood smear of HbC
HbC crystals + target cells
38
What is the role of decay accelerating factor (DAF)
Inhibits C3 convertase
39
What cells are lysed in paroxysmal nocturnal hemoglobinuria
RBCs, WBCs, and platelets are lysed via intravascular hemolysis
40
Main cause of death in paroxysmal nocturnal hemoglobinuria
Thrombosis of hepatic, portal or cerebral vines
41
Complications of paroxysmal nocturnal hemoglobinuria
- Iron deficiency anemia (due to chronic loss of hemoglobin in the urine)
- Acute myeloid leukemia (AML) [develops in 10% of patients]
42
G6PD deficiency is due to
Reduced half-life of G6PD, not a deletion
43
Myelophthisic process
Pathologic process (eg metastatic cancer) that replaces bone marrow and impairs hematopoiesis, resulting in pancytopenia.
44
High cortisol state and white cells
- Causes lymphopenia (induces apoptosis of lymphocytes)
| - Cause neutrophilic leukocytosis (impairs leukocyte adhesion, leading to release of marginated pool of neutrophils)
45
Characterize a left shift
Release of immature forms of leukocytes, which are characterized by decreased Fc receptors (CD16)
CD16 is generally found on NK cells and binds the Fc region of IgG
46
Bordatella pertussis infection
Bacteria produce lymphocytosis promoting factor, which blocks circulating lymphocytes from leaving the blood to enter the lymph node
47
Definitive diagnosis of infectious mononucleosis
Serologic testing for EBV viral capsid antigen
48
Complications associated with infectious mononucleosis
Dormancy of irus in B cells leads to increased risk for both recurrence and B cell lymphoma, especially if cases of immunodeficiency develops
49
Describe blasts on blood smear
Large immature cells often with punched out nucleoli
50
Marker for acute lymphoblastic leukemia (ALL)
- TdT, a DNA polymerase
| - Absent in myeloid blasts and mature lymphocytes
51
Demographic of acute lymphoblastic leukemia (ALL)
- Children
- Associated with Down syndrome (usually arises after the age of 5)
- Subclassified into B-ALL and T-ALL
52
Markers for B-ALL
- TdT +
| - CD10, CD19, CD20
53
Cytogenetics for B-ALL
- t(12,21) → children → good prognosis
| - t(9,22) → adults → poor prognosis
54
Markers for T-ALL
- TdT +
| - CD2-CD8
55
Marker for acute myeloid leukemia (AML)
- MPO, myeloperoxidase
| - May be seen as Auer rods
56
Demographic of acute myeloid leukemia (AML)
Older adults
57
Subtypes of acute myeloid leukemia (AML)
ACUTE PROMYELOCYTIC LEUKEMIA (APL)
- t(15,17)
- Translocation of the retinoic acid receptor
- Contain numerous primary granules that increase risk for DIC
ACUTE MONOCYTIC LEUKEMIA
- Lack MPO
- Characteristically infiltrate gums
ACUTE MEGAKARYOBLASTIC LEUKEMIA
- Proliferation of megakaryoblasts
- Lack MPO
- Associated with Down syndrome (usually arises before the age of 5)
58
Markers of chronic lymphocytic leukemia (CLL)
Neoplastic proliferation of naive B cells that co-express CD5 and CD20
59
Involvement of chronic lymphocytic leukemia (CLL) with lymph nodes
Leads to generalized lymphadenopathy and is called small lymphocytic lymphoma
60
Complications of chronic lymphocytic leukemia (CLL)
- Hypogammaglobulinemia (infection is the most common cause of death)
- Autoimmune hemolytic anemia
- Transformation to diffuse large B-cell lymphoma (Richter transformation) - marked clinically by an enlarging lymph node or spleen
61
Marker of hairy cell leukemia
Neoplastic proliferation of mature B cells characterized by hairy cytoplasmic processes and are positive for tartrate-resistant acid phosphatase (TRAP)
62
Clinical features of hairy cell leukemia
- Splenomegaly (accumulation of hairy cells in red pulp)
- Dry tap on bone marrow aspiration (due to marrow fibrosis)
- Lymphadenopathy is ABSENT
63
Clinical features of adult T-cell leukemia/lymphoma
- Neoplastic proliferation of mature CD4+ T cells
- Rash (skin infiltration)
- Generalized lymphadenopathy with hepatosplenomegaly and lytic (punched out) bone lesions with hypercalcemia
64
Clinical features of mycosis fungoides
- Neoplastic proliferation of mature CD4+ T cells that infiltrate the skin
- Localized skin rash, plaques and nodules
- Aggregates of neoplastic cells in the epidermis are called Pautrier microabscesses
65
Cytogenetics of chronic myeloid leukemia (CML)
- t(9,22)
- BCR-ABL fusion
- Mutation is in a pluripotent stem cell
66
Enlargening spleen in chronic myeloid leukemia (CML)
- Suggests progression to accelerated phase of disease
- Transformation to acute leukemia usually follows shorty therafter
- Can transform to AML (2/3 of cases) or ALL (1/3 of cases) since mutation is in pluripotent stem cell
67
Cytogenetics of polycythemia vera
Associated with JAK2 kinase mutation
68
Cytogenetics of essential thrombocythemia
Associated with JAK2 kinase mutation
69
Cytogenetics of myelofibrosis
Associated with JAK2 kinase mutation in 50% of cases
70
Cause of marrow fibrosis in myelofibrosis
Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing marrow fibrosis
71
Types of small B cell non-Hodgkin lymphoma
- Follicular lymphoma
- Mantle cell lymphoma
- Marginal lymphoma
- Small lymphocytic lymphoma (CLL that involves tissues_
72
Type of intermediated sized B cell non-Hodgkin lymphoma
Burkitt lymphoma
73
Type of large B cell non-Hodgkin lymphoma
Diffuse large-B cell lymphoma
74
In which cancer does a leukemic phase occur - Hodgkin or non-Hodgkin lyphoma?
Leukemic phase only occurs in non-Hodgkin lymphoma
75
Cytogenetics of follicular lymphoma
- t(14,18)
- BCL2 on chromosome 18 translocates to Ig heavy chain locus on chromosome 14
- Results in overexpression of Bcl2, which inhibits apoptosis
76
Complication of follicular lymphoma
Progression to diffuse large B cell lymphoma (presents as an enlarging lymph node)
77
Cytogenetics of mantle cell lymphoma
- t(11,14)
- Cyclin D1 on chromosome 11 translocates to Ig heavy chain locus on chromosome 14
- Overexpression of cyclin D1 promotes G1/S transition in the cell cycle, facilitating neoplastic proliferation
78
Marginal zone lymphomas are associated with
- Chronic inflammatory states such as Hashimoto thyroiditis, Sjogren syndrome and H pylori gastritis
- Keep in mind that the marginal zone is formed by post-germinal center B cells
79
MALToma
- A marginal zone lymphoma located in mucosal sites
| - Gastric MALToma may regress with treatment of H pylori, unless patient has Trisomy 3
80
Cytogenetics of Burkitt lymphoma
- t(8,14)
- Most common translocation of c-myc on chromosome 8 to Ig heavy chain locus on chromosome 14
- Overexpression of c-myc oncogene promotes cell growth
81
Type of lymphoma associated with "B symptoms"
- Hodgkin lymphoma
| - Fever, chills, weight loss, and night sweats
82
Subtypes of Hodgkin lymphoma
NODULAR SCLEROSIS
- Most common subtype
- Occurs in young adult females
- Lymph node is divided by bands of sclerosis and RS cells are present in lake-like spaces (lacunar cells)
LYMPHOCYTE-RICH
- Best prognosis
MIXED CELLULARITY
- Abundant eosinophils (RS cells produce IL-5)
LYMPHOCYTE-DEPLETED
- Most aggressive
- Usually seen in the elderly and HIV+ individuals
83
Marker for non-Hodgkin lymphoma
CD20+
84
Markers for Hodgkin lymphoma
CD15+ and CD30+
85
Cause of lytic bone lesions and hypercalcemia in multiple myeloma
Neoplastic plasma cells activate the RANK receptor on osteoclasts, leading to bone destruction
86
Presentation of monoclonal gammopathy of undetermined significance (MGUS)
- Increased serum protein with M spike on SPEP
| - ABSENCE of lytic bone lesions, hypercalcemia, AL amyloid or Bence Jones proteinuria)
87
Markers of Langerhans cell histiocytosis
CD1a+ and S100+
S100 also seen in melanoma and schwannoma
88
Clinical presentation of Langerhans cells histiocytosis
LETTERER-SIWE DISEASE
- Malignant
- Skin rash and cystic skeletal defects
- Multiple organ involvement possible
- Infants
EOSINOPHILIC GRANULOMA
- Benign
- No skin involvement
- Pathologic fracture
- Adolescent
HAND-SCHULLER-CHRISTIAN DISEASE
- Malignant
- Scalp rash, lytic skull defects, diabetes insipidus, and exophthalmos in a child
89
Pathology of temporal (giant cell) arteritis
- Granulomatous vasculitis that involves branches of the carotid artery
- Biopsy reveals inflamed vessel wall with giant cells and intimal fibrosis
- Lesions are segmental
90
Pathology of Takayasu arteritis
Granulomatous vasculitis that classically involves the aortic arch at branch points
91
Pathology of polyarteritis nodosa
- Early lesion consists of transmural inflammation with fibrinoid necrosis that eventually heals with fibrosis, creating a "string of pearls" appearance on imaging
- Usually involves renal artery (hypertension), mesenteric artery (abdominal pain with melena) as well as other arteries to cause skin lesions and neurologic disturbances
- Lungs are spared
92
Pathology of Buerger disease
Necrotizing vasculitis involving the digits
93
Pathology of Wegener granulomatosis
Necrotizing granulomatous vasculitis involving nasopharynx, lungs and kidneys
94
Pathology of microscopic polyangiitis
- Necrotizing vasculitis involving multiple organs, especially lung and kidney
- Abssent nasopharyngeal involvement
- No granulomas
95
Pathology of Churg-Strauss syndrome
- Necrotizing granulomatous inflammation with eosinophils involving multiple organs, especially lungs and heart
- Asthma and peripheral eosinophils are often present
96
Pathology of Henoch-Schonlein purpura
Vasculitis due to IgA immune complex deposition
97
Fibromuscular dysplasia
- Developmental defect of the blood vessel wall
- Results in irregular thickening of large and medium sied arteries, especially the renal artery
- Important cause of secondary hypertension in young females
98
Pathogenesis oft atherosclerosis
1. Damage to endothelium allows lipids to leak into the intima
2. Lipids are oxidized and then consumed by macrophages via scavenger receptors resulting in foam cells
3. Inflammation and healing leads to deposition of extracellular matrix and proliferation of smooth muscle
99
Angiosarcoma
- Malignant proliferation of endothelial cells
- Highly aggressive
- Common sites include skin, breast, and liver
- Liver angiosarcoma is associated with exposure to PVC, arsenic, and thorotrast
Step 1
flashcards
Decks in class (25)
# Cards
-
UWorld223
-
Autoantibodies25
-
HLA subtypes associated with diseases8
-
Common diseases of HIV-positive adults23
-
Common causes of pneumonia13
-
Common causes of meningitis6
-
Nosocomial infections8
-
Bugs affecting unvaccinated children10
-
Important cytokines15
-
Cell surface proteins9
-
Drug reactions47
-
Random pharmacology82
-
Pathoma99
-
Signaling pathways of endocrine hormones6
-
Gastrointestinal regulatory substances36
-
Endocrine42
-
GI77
-
Reproductive167
-
Respiratory50
-
Cardiovascular144
-
MSK, Skin and Connective Tissue117
-
Renal114
-
Hematology and Oncology120
-
Neurology193
-
Pathology107
