Hematology Flashcards
(446 cards)
1
Q
HML Embryology:
When does the liver make itself the major site of hematopoiesis?
A
Week 9
2
Q
HML Embryology:
How long does the spleen remain exclusively a hematopoietic organ?
What occurs after that? (2 points)
A
- 14 weeks
- 15-18 weeks: T cell precursors
- 23 weeks: B cell precursors enter. the spleen and form B- cell regions
3
Q
HML Embryology:
Why does hemoglobin exhibit a sigmoid shape on the Oxygen dissociation curve?
A
Because it’s an allosteric molecule and exhibits positive cooperatively. Allowing for efficient loading and unloading of oxygen.
4
Q
HML Embryology:
What causes a right shift in the Hb dissociation curve?
A
Elevation in H+, CO2, 2,3-bisphosphoglycerate, and temperature. Favoring unloading.
5
Q
HML Embryology:
What is difference between the T and R form of Hb?
A
- T (taut) is the deoxygenated form and has a lower affinity for oxygen to bind.
- R (relaxed) is the oxygenated form and has 300x more affinity
6
Q
HML Embryology:
Where is fetal hemoglobin made? What is made up of and why is it important?
A
- Made in the fetal liver
- made up of two alpha and 2 gamma chains
- has higher affinity to oxygen than adult Hb.
7
Q
HML Embryology:
When does the transition of fetal Hb to adult Hb complete?
A
6 months of age
8
Q
HML Embryology:
What is the importance in the relationship between fetal Hb and 2,3-BPG?
A
Fetal Hb does not bind to 2,3-BPG, resulting in an increased affinity for oxygen.
9
Q
HML Anatomy:
How much of the total blood volume is made up of plasma?
A
55%, blood cells (RBCs, WBCs, and platelets) occupy the rest of the 45%
Rich in proteins, hormones, electrolytes, and small molecules
10
Q
HML Anatomy:
What is serum?
A
Plasma without the clotting factors.
11
Q
HML Anatomy:
What is the effect of corticosteroids on polymorphonuclear neutrophil (PMN) migration?
A
- inhibit PMN from the circulation into the periphery
- causing benign leukocytosis. They also cause apoptosis of lymphocytes and sequestration of eosinophils in lymph nodes.
12
Q
HML Anatomy:
Do RBCs utilize aerobic metabolism?
A
No
13
Q
HML Anatomy:
How does the RBC utilize energy?
A
Source = glucose
90% anaerobically resulting into lactate,
10% hexose monophosphate HMP shunt to produce NADPH (reduced)
14
Q
HML Anatomy:
What accounts for 0.5-1.5% of RBCs?
A
Reticulocytes
15
Q
HML Anatomy:
What is normal range of WBCs?
A
4,000 to 11,000/úL
16
Q
HML Anatomy:
What is the prevalence of the different WBC?
A
Mneumonic: ‘Never Let Monkeys Eat Bananas
- Neutrophils (54-62%)
- Lymphocytes (25-33%
- Monocytes (3-7%)
- Eosinophils (1-3%)
- Basophils (0-0.75%)
17
Q
HML Anatomy:
How can you determine if an anemia is hypo/hyperproliferative?
A
- Corrected HCT (hematocrit)
= HCT/45; <2% then hypo, >3% is hyper
18
Q
HML Anatomy:
What are the two types of abnormal neutrophils?
A
Immature (bands) and hypersegmented
19
Q
HML Anatomy:
What conditions would you see “band” neutrophils?
A
Bacterial infections, leukemias, and other inflammatory conditions
- neutrophils are horseshoe shaped
20
Q
HML Anatomy:
What conditions would you see hypersegmented neutrophils?
A
Macrocytic anemias associated with Vitamin B12 and folate deficiencies
- Neutrophils with more than five lobes
21
Q
HML Anatomy:
What does hematocrit mean?
A
Represents the percentage of whole-blood volume composed of erythrocytes
22
Q
HML Anatomy:
What does mean cell hemoglobin mean?
A
The average content of hemoglobin per RBC
23
Q
HML Anatomy:
What does MCHC mean?
A
- Mean corpuscular hemoglobin concentration
- The average concentration of hemoglobin in a given volume of packed RBCs. The MCHC is low if the RBCs are hypochromic
24
Q
HML Anatomy:
What does RDW mean?
A
- RBC distribution width
- The coefficient of variation of RBC volume. An increased RDW means that the RBCs vary greatly in size.
25
HML Anatomy:
What is the importance of lactoferrin in neutrophils?
Binds to iron so bacteria cannot utilize leading to bacterial death
26
HML Anatomy:
What are the five chemostatic agents in neutrophils?
C5a, IL-8, LTB4, kallikrein, and platelet-activation factor
Mneumonic: CKLIP (Clip)
27
HML Anatomy:
Where do B lymphocytes migrate towards after maturing in the bone marrow? 3
Peripheral lymphoid tissues (lymph node follicles, white pulp of spleen, and unencapsulated lymphoid tissue)
28
HML Anatomy:
Which immunoglobulins do B lymphocytes need to recognize first before plasma cell differentiation and antibody production?
IgM and IgD
29
HML Anatomy:
What do B lymphocytes function as?
3 points
Memory cells, APCs, and express MHC class II
30
HML Anatomy:
What are the CD markers for B lymphocytes?
CD19, CD20, CD21
31
HML Anatomy:
What T lymphocytes differentiate to?
- Cytotoxic T cells
- Helper T cells
- Suppressor T cells
- delayed hypersensitivity T cells
32
HML Anatomy:
Describe the mechanism how a T cells get activated:
First binds the antigen to the MHC complex, then sends a co-stimulatory signal via CD28/CD40L.
33
HML Anatomy:
Describe how you identify a plasma cell under a microscope:
Eccentric cells with purple "clock-faced" nuclei, cytoplasm has abundant blue rough endoplasmic reticulum and well developed Golgi apparatus.
34
HML Anatomy:
Which lymphocyte can mediate both adaptive and innate immunity responses?
Natural Killer cells (NK cells)
35
HML Anatomy:
What are the CD markers for NK Cells?
CD16 and CD56
36
HML Anatomy:
What is contained in the cytoplasm of the NK cell?
- Small granules filled with perforin and granzyme
- induces apoptosis to help target and kill cells lacking MCH I, including tumor-derived cells and cells infected with viruses.
37
HML Pathology:
Describe Leukocyte adhesion deficiency (LAD):
An autosomal recessive defect of integrant (CD18 subunits), resulting in delayed separation of the umbilical cord, increased circulating PMN leukocytes, recurrent bacterial infections (lack of pus formation), severe gingivitis, and poor wound healing.
38
HML Anatomy:
What are the five common causes of eosinophilia?
Mneumonic NAACP:
- Neoplasia
- Asthma
- Allergic processes
- Collagen vascular diseases
- Parasites
39
HML Anatomy:
What is the shape of the nucleus of a Monocyte?
Kidney shaped
40
HML Anatomy:
What is contained in the cytoplasm of the monocyte?
Azurphilic granules (lysosomes) and appear basophilic with a "frosted glass appearance.
41
HML Anatomy:
What accounts for 2-10% of all leukocytes?
Monocytes, they are the precursors for macrophages and APCs
42
HML Anatomy:
Describe how an eosinophil looks under a microscope:
Bilobed cell with large eosinophilic granules.
43
HML Anatomy:
What percentage of leukocytes do eosinophils comprise of?
1-6%
44
HML Anatomy:
How do eosinophils defend against parasitic infections?
Major basic protein
45
HML Anatomy:
Name the chemical mediators released by eosinophils:
Leukotrienes, prostaglandins E1 and E2, thromboxane B2, and platelet-activating factor
46
HML Anatomy:
How do eosinophils down regulate allergic reactions?
Histaminase inactivate the basophil-derived substrate histamine
47
HML Anatomy:
Which leukocyte has a causative role in allergic reactions, are bilobed, and have deep basophilic granules?
Basophils
48
HML Anatomy:
What percentage of leukocytes do basophils account for?
<0.5%
49
HML Anatomy:
What receptor is activated on basophils?
What is released?
What conditions would you see this in?
- IgE receptors
- release of histamine, heparin, prostaglandins, leukotrienes, and other vasoactive amines.
- Seen in asthma, hay fever, and elevated in myeloproliferative diseases.
50
HML Anatomy:
Which Leukocyte is abundant near blood vessels and in tissue exposed to the external environment (eg skin, respiratory, GI, urogenital)?
Mast cells
51
HML Anatomy:
Which leukocyte is similar to basophils, express IgE receptors and counter parasitic infections and chronic allergic diseases?
Mast cells
52
HML Anatomy:
Describe the three ways Mast cells can be activated:
1. Cross-linking of cell surface IgE by antigen
2. Complement C3a/C5a
3. Tissue trauma: Histamine (from immediate response) vs leukotrienes (delayed response)
53
HML Pharmacology:
Describe the action and clinical use for Cromolyn sodium:
- Prevents mast cell degranulation, used for asthma prophylaxis.
54
HML Pharmacology:
Describe the action and clinical use for Omalizumab:
Inhibits IgE binding to mast cells. Used for severe allergic asthma.
55
HML Anatomy:
How would you describe a macrophage under a microscope?
Oval nuclei and blue-gray to pale cytoplasm
56
HML Anatomy:
Which leukocytes serve as tissue scavengers, are phagocytic, consumes bacteria, ages RBCs, cell debris, and has an APC property?
Macrophages
57
HML Anatomy:
How are macrophages activated?
Gamma interferon
58
HML Anatomy:
Describe four different derivatives of macrophages in different organs and tissues:
- Kupffer cells in the liver
- Microglial cells in the brain
- Osteoclasts in the bone
- Mesangial cells in the kidney (derived from monocytes)
59
HML Anatomy:
Which Leukocytes are the sentinels, adjuvants, and controllers of both innate and adaptive immunities?
Dendritic cells
60
HML Anatomy:
How do dendritic cells serve as APCs?
Expressing major histocompatibility complex (MHC) II and crystallizable fragment (Fc) receptors on their surface.
61
HML Anatomy:
Which leukocytes are the main inducers of the primary antibody response?
Dendritic Cells
62
HML Anatomy:
What are dendritic cells of the skin called?
Langerhans cells
63
HML Pathology:
Describe the relevant signs and symptoms for an anemia caused by hypoxia:
General weakness or fatigue, dyspnea or angina on exertion, or syncope, pale conjunctiva or skin, and koilonychias (spoon shaped nails)
64
HML Pathology:
Describe the relavant signs and symptoms for an anemia caused by an increased cardiac output:
Tachycardia or palpitation, systolic murmur, or high-output heart failure.
65
HML Pathology:
List the 5 categories that can cause a microcytic anemia:
Mneumonic: TAILS
1. Iron deficiency (late)
2. ACD (late)
3. Thalassemias
4. Lead poisoning
5. Sideroblastic anemia (copper deficiency can also cause this)
66
HML Pathology:
List the 4 circumstances where you would see a normocytic-nonhemolytic (reticulocyte count normal/decreased) anemia?
1. Iron deficiency (early)
2. ACD (Early)
3. Aplastic Anemia
4. Chronic Kidney disease
67
HML Pathology:
List the 5 circumstances where you would see a normocytic-hemolytic (reticulocyte count increase) anemia in an intrinsic matter:
1. RBC membrane defect: hereditary spherocytsosis
2. RBC enzyme deficiency: G6PD, pyruvate kinase
3. HbC disease
4. Paroxysmal nocturnal hemoglobinuria
5. Sickle cell anemia
68
HML Pathology:
List the 4 circumstances where you see a normocytic-hemolytic (reticulocyte count increase) anemia in an extrinsic matter:
Mneumonic: AIIMM
1. Autoimmune
2. Microangiopathic
3. Macroangiopathic
4. Infections
69
HML Pathology:
List the 3 circumstances where you see a macrocytic-megaloblastic anemia:
1. Folate deficiency
2. B12 deficiency
3. Orotic aciduria
70
HML Pathology:
List the 3 circumstances where see a macrocytic-nonmegaloblastic anemia:
1. Liver disease
2. Alcoholism
3. Diamond-Blackfan anemia
71
HML Pathology:
List 2 common conditions affiliated with acanthocytes: RBCs with spiny processes protruding from cell surface
Abetalipoproteinemia and liver disease
72
HML Pathology:
List 2 common conditions affiliated with basophilic stipping: RBCs with numerous small purplish dots
Lead poisoning, thalassemias
73
HML Pathology:
What is a common associated condition relating with Dacrocyte? ("teardrop cell")
Myelofibrosis
74
HML Pathology:
What is a common condition associated with Degmacyte? ("bite cell")
Glucose-6-phosphate dehydrogenase deficiency
75
HML Pathology:
List 2 common conditions associated with Elliptocytes:
Hereditary elliptocytosis and Iron deficiency
76
HML Pathology:
What is a common condition associated with Heinz body?
Glucose-6-phosphate dehydrogenase deficiency
77
HML Pathology:
List 2 common conditions associated with Howell-Jolly bodies:
Asplenia and functional hyposplenia
78
HML Pathology:
What is a common condition associated with macro-ovalocyte?
Megaloblastic anemia
79
HML Pathology:
What is a common condition associated with ringed sideroblast?
Lead poisoning
80
HML Pathology:
What is a common conditions associated with schistocyte?
2 points
1. Disseminated intravascular coagulation
2. Thrombotic thrombocytopenia purpura
81
HML Pathology:
List 2 common condition associated with Spherocytes:
1. Hereditary spherocytosis
2. Autoimmune hemolysis
82
HML Pathology:
List 4 common condition associated with Target cells:
4 points
(HALT mneumonic)
1. Thalassemia
2. Liver disease
3. Hemoglobin C disease
4. Aspenia
83
HML Pathology:
List 4 common causes of GI bleeding:
1. Endometrial polyps in adult female
2. Peptic ulcer in adult male
3. Colon polyps/carcinoma in elderly
4. Hookworm in developing countries (Ancylostoma Duodenale, Necator Americanus)
84
HML Pathology:
How can Iron deficiency be caused? 3 categories
1. Increased requirement: Pregnancy, infants, and preadolescents
2. Dietary deficiency: Exclusively breast-fed infants after 6 months of age, elderly
3. Chronic blood loss: Menorrhagia, gastrointestinal bleeding
85
HML Pathology:
Describe the triad for Plummer-Vinson syndrome:
1. Upper esophageal web (dysphagia)
2. Iron deficiency
3. Atrophic glossitis
86
HML Pathology:
How can you diagnose an Iron deficiency anemia?
1. Decreased hemoglobin and hematocrit
2. Decreased serum iron
3. Increased total iron-binding capacity (TIBC)
4. Decreased ferritin
5. PBS will show microcytic, hypochromic RBCs
87
HML Pathology:
What are 4 common country population are Thalassemias among?
1. African
2. Indian
3. Southeast Asian
4. Mediterranean
88
HML Pathology:
How many types of thalassemias are there?
2; alpha and beta
89
HML Pathology:
What is the underlying mechanism that makes beta-thalassemia develop?
Point mutation in either the promoter region or the splicing sites on chromosome 11, forming a premature stop or reduced production.
90
HML Pathology:
What is an alternate name for beta-thalessemia?
Mediterranean/ Cooley anemia
91
HML Pathology:
How many different forms of beta-thalassemia are there?
3; Minor (Beta/Beta+), Major (B0/B0), HbS/Beta-thalassemia
92
HML Pathology:
Describe beta thalassemia minor:
Heterozygote, clinically asymptomatic, lab studies show elevated HbA2
93
HML Pathology:
Describe beta thalassemia major:
Homozygote with absent Beta globin chain, resulting in severe anemia
94
HML Pathology:
Describe HbS/Beta-thalassemia:
- Combo of sickle cell and beta-thalassemia
- Mc in USA and Mediterrannean
- Mild to moderate presentation depending on Beta global production
95
HML Pathology:
What does alpha-aggregation mean?
- clumping of alpha-globin chains in beta-thalassemia major (lacks HbA)
- leads to decreased RBC life span, apoptosis of its precursors, then ineffective erythropoeisis
- Fetal Hb in increased but not adequate
96
HML Pathology:
How does beta thalassemia present: 3 S's
- anemia: severe anemia months after birth
- splenomegaly: extra medullary hematopoiesis (increase EPO)
- Skeletal deformities: thinning of cortical bone nan peripheral new bone formation, "crew cut" and "chipmunk face"
- HemoSiderosis: iron overload from repeated transfusions
97
HML Pathology:
What are patients with beta thalassemia at increased risk for?
Aplastic crisis due to parvovirus B19 (ssDNA non enveloped, dx: fecal testing)
98
HML Pathology:
How do you diagnose and treat beta-thalassemia?
Dx:
- Hb electrophoresis
- PBS: Target cells, microcytosis, and hypochromic
Tx:
- blood transfusions (increased risk for secondary hemochromatosis
99
HML Pathology:
What is the prognosis for beta-thalassemia?
4 points
- growth retardation
- death at an early age
- cardiac failure
- other organ damage from hemosiderosis
100
HML Pathology:
What is the mechanism behind the development of alpha-thalassemia?
- gene mutation or deletion in one or more of the four alpha-globing genes on chromosome 16
- relative excess of other chains including beta, gamma, and delta
101
HML Pathology:
How does alpha-thalassemia present, in the silent carrier state?
Only one alpha globin gene affected; asymptomatic
102
HML Pathology:
How does alpha-thalassemia present, with the alpha-thalassemia trait?
- two genes deleted
- similar to beta-thalassemia minor with minimal anemia
103
HML Pathology:
How does alpha-thalassemia present, in the HbH state?
- three genes affected
- tetramers of beta-globin chains form which have a high affinity for oxygen, and also damages RBCs, leading to hemolysis, anemia disproportionate to the amount of Hb
104
HML Pathology:
How does alpha-thalassemia present, in the Hb Bart state?
- deletion of all four genes
- stable tetramers of gamma-globin chains form with extremely high affinity for oxygen
- severe anemia
- leads to intrauterine death (Hydrops Fetalis) unless intrauterine transfusion is performed
- fetus shows edema, pallor, and hepatosplenomegaly
105
HML Pathology:
How would you diagnose alpha-thalassemia?
- Hb Electrophoresis
- PBS: microcytic and hypochromic
- molecular genetic testing showing alpha-thalassemia traits
106
HML Pathology:
What is worse for alpha-thalassemia trait: the cis deletion or the trans?
- Cis deletion on same chromosome is worse, common in asian populations, there is an increased risk of spontaneous abortion and severe thalassemia in offspring
- Trans deletion occurs on separate chromosomes, common in African American populations. No increased risk.
107
HML Pathology:
What two enzymes are inhibited when exposed to lead?
1. ALAD: aminolevulinic acid dehydratase
2. Ferrochelatase
108
HML Pathology:
What occupations or settings are we concerned about lead poisoning?
3 points
- Miners
- Industrial workers (exposure to lead batteries)
- houses built on or before 1978
109
HML Pathology:
How does lead poisoning present?
- abdominal pain
- peripheral neuropathy (eg wrist and foot drop)
- encephalopathy
- characteristic Burton lines on gingiva and metaphases of long bone
110
HML Pathology:
How would you diagnose lead poisoning?
- PBS: basophilic stippling (aggregated rRNA)
- hypochromic microcytic anemia or sideroblastic anemia
111
HML Pharmacology:
How would you treat lead poisoning?
- Children: Succimer
- Dimercarprol and ethylenediaminetetraacetic acid (EDTA)
112
HML Pathology:
Describe sideroblastic anemia:
- defective protoporphyrin synthesis
- genetic (congenital defects of aminolevulinic acid synthetase (ALAS)
- X-linked
- acquired causes (eg, alcoholism, lead poisoning, and vitamin B6 deficiency)
113
HML Pathology:
How do you diagnose sideroblastic anemia?
- special staining of bone marrow aspirate for iron showing ringed sideroblasts (trapped iron in mitochondria)
- Lab studies: increased ferritin, decreased TIBC, increased serum iron saturation
114
HML Pharmacology:
How do you treat sideroblastic anemia?
Pyridoxine (vitamin B6) cofactor for Aminolevulinic acid synthase (ALAS)
115
HML Pathology:
What is the pathophysiology underlying megaloblastic anemia?
Deficiency in vitamin B12 or folate (coenzymes in DNA synthesis) leads to delayed DNA replication, cytoplasmic maturation is normal
116
HML Pathology:
What are some causes of nonmegaloblastic, macrocytic anemia?
4 points
Mneumonic: HAAL
- Alcoholism
- liver disease
- hypothyroidism
- anticancer drugs (5-FU)
117
HML Pathology:
How can vitamin B12 deficiency be caused?
- Decreased intake (vegans)
- Impaired absorption (PPIs, pancreatic insufficiency, pernicious anemia, gastrectomy, malabsorption, ill resection, Diphyllobothrium datum /fish tapeworm infection, blind loop syndrome, broad spectrum antibiotics
- Increased requirement (pregnancy, hyperthyroidism)
118
HML Pathology:
How can folic acid deficiency be caused?
5 points
- Decreased intake (alcoholics and elderly)
- impaired absorption (sprue, phenytoin, oral contraceptives)
- increased loss (hemodialysis)
- increased requirement (pregnancy, infancy, increased hematopoiesis)
- folic acid antagonist chemotherapy (methotrexate)
119
HML Pathology:
Describe subacute combined degeneration:
Vitamin B12 deficiency leads to demyelination of the dorsal and lateral columns of the spinal cord. Results in ataxia (spinocerebellar tract), hyperreflexia (lateral corticospinal tract), and decreased potion and vibration sensation (dorsal column)
120
HML Pathology:
How does a megaloblastic anemia present?
Anemia, glossitis, and
subacute combine degeneration (vitamin 12, impaired myelination form elevated toxic methylmalonic acid buildup)
121
HML Pathology:
If you have a child pt with a megaloblastic anemia that is not responding to folate or vitamin B12 supplementation, what should you suspect?
Orotic aciduria:
- a genetic mutation in uridine monophosphate synthase (converts orotic acid to uridine in pyrimidine synthesis). Orotic acid in the urine.
- Tx: Uridine monophosphate
122
HML Pathology:
How would you diagnose and treat a megaloblastic anemia?
- PBS: pancytopenia, oval macrocytosis, and hyperhsegmented neutrophils (> 5 lobes)
- Bone marrow: megaloblastic hyperplasia
- Labs for folate deficiency: Decreased serum folate, elevated homocysteine, and normal methylmalonic acid
- Labs for vitamin b12 deficiency: decreased vitamin b12, elevated homocysteine, and increased methylmalonic acid
- Tx: Vitamin B12 with or without Folate
123
HML Pathology:
How does a pernicious anemia develop?
anti-intrinsic factor antibodies
124
HML Pathology:
What is a Schilling test used for?
5 points
To confirm/correct a vitamin b12 deficiency caused by either:
1. Impaired absorption: oral Vitamin B12 after saturation via IM
2. Pernicious anemia: oral Vitamin B12 + IF
3. Bacterial overgrowth: B12 + antibiotics
4. Pancreatic insufficiency: B12 + pancreatic enzymes (R-binder)
125
HML Pathology:
What is the inheritance pattern of Glucose-6-phosphate dehydrogenase deficiency?
XLR, leads to abnormally folded enzyme subjected to proteolysis.
126
HML Pathology:
What ethnic populations is G6PD deficiencies more prevalent in?
3 points
Black, Middle Eastern/ Mediterranean populations
127
HML Pathology:
What kind of hemolysis is seen in G6PD deficiency?
Both intravascular and extravascular
128
HML Pathology:
How does G6PD deficiency present? 5 points
- often symptomatic
- hx of neonatal jaundice and cholelithiasis
- episodic fatigue, pallor, hemoglobinuria, and back pain (Hb Nephrotoxicity) days after oxidant stress
- PE shows jaundice and splenomegaly
- Hemolysis from exposure to oxidative stress
129
HML Pathology:
How does hemolysis occur in G6PD deficiency? 3 categories
- exposure to oxidative stress from:
-- Drugs: Sulfonamides, dapsone, primaquine, chloroquine, and nitrofurantoin, etc.
-- Infections: viral hepatitis, typhoid fever, pneumonia
-- Others: Fava beans
130
HML Pathology:
How would you diagnosis G6PD deficiency? 6 points
- Measure G6PD enzyme activity after resolved hemolytic episodes
- increased indirect bilirubin, decreased serum haptoglobin
- decreased hematocrit and hemoglobinemia in CBC
- Heinz bodies and bite cells (splenic removal)
- Hemoglobinuria in urinalysis
- splenomegaly and gallstones in abdominal US (increased indirect bilirubin)
131
HML Pathology:
How do you treat G6PD deficiency? 4 points
- avoid precipitating factors
- provide oxygen and rest during episodes
- exchange transfusions if severe
- phototherapy in infants
132
HML Pathology:
What is the prognosis in G6PD deficiency?
- healthy if avoiding predicating factors
- complicated by neonatal jaundice leading to kernicterus
133
HML Pathology:
Describe Chediak-Higashi syndrome: 3 points
- autosomal recessive
- lysosomal trafficking defect characterized by impaired phagolysosome formation
- results in increased pyogenic infection, neutropenia, albinism, defective primary hemostasis, and peripheral neuropathy
134
HML Pathology:
Describe Chronic Granulomatous disease: 4 points
- XLR inheritance
- defect in NADPH
- Poor O2-dependent killing, resulting in recurrent infection and granuloma formation with catalase-positive organisms.
- Nitroblue tetrazolium test result is negative
135
HML Pathology:
What is the inheritance pattern of Hereditary Spherocytosis?
Autosomal dominant
136
HML Pathology:
What is deficient in Hereditary Spherocytosis?
- Spectrin, ankyrin, and other membrane tethering cytoskeletal proteins (vertically) like band 3, and protein 4.2, decreasing RBC fragility
137
HML Pathology:
What is the difference between Hereditary spherocytosis and hereditary elliptocytosis?
Hereditary elliptocytosis has a defect in tethering proteins involving horizontal interactions (spectral, protein 4.1, and glycophorin)
138
HML Pathology:
How does Hereditary Spherocytosis present? 4 points
- anemia, splenomegaly, and jaundice
- predominantly extravascular hemolysis
- may develop cholelithiasis (bilirubin gallstones)
- positive family history
139
HML Pathology:
How is hereditary spherocytosis diagnosed? 4 points
What are the differentials? 4 points
- RBC lysis in hypotonic salt (osmotic fragility test)
- Increase MCHC (pathognomonic, but also seen in cold-agglutinin anemia) due to dehydration
- PBS: Spherocytes
- minimal anemia with reticulocytosis in CBC, and increased indirect bilirubin
- DDX includes anemia, biliary disease, hyperbilirubinemia, and AIHA (also have spherocytes)
140
HML Pathology:
How do you treat hereditary spherocytosis? 4 points
- splenectomy
- transfusions if severe
- phototherapy in infants
- supplemental folic acid and iron for increased RBC turnover
141
HML Pathology:
What is the prognosis of Hereditary Spherocytosis? 4 points
- aplastic crisis triggered by parvovirus B19
- infections after splenectomy
- cholelithiasis (bilirubin gallstones)
- hemosiderosis from multiple blood transfusions
142
HML Pathology:
Describe Myeloperoxidase deficiency disease:
- results from defective conversion from H2O2 to HOCl, leading to an increased risk for Candida infections. However, most patients remain asymptomatic (vs CGD)
143
HML Pathology:
What are the three types of immunohemolytic anemias?
- Warm antibody
- Cold agglutinin
- erythroblastosis fetalis
144
HML Pathology:
What is the mnemonic to distinguish between Warm antibody vs Cold agglutinin?
- Warm is GGGreat (IgG)
- Cold ice cream MMM (IgM)
145
HML Pathology:
What is the shape and consequence of the RBCs in Warm Antibody Hemolytic anemia?
- Spherocytes
- Sequestered then phagocytose in the spleen, a form of extravascular hemolysis
146
HML Pathology:
How does Warm antibody hemolytic anemia present? 3 points
- elevated bilirubin (jaundice, pigment gallstones)
- reticulocytosis
- splenomegaly
147
HML Pathology:
What conditions are associated with warm antibody hemolytic anemia? 4 points
Memory Aid: Rule of L's
- SLE
- Hodgkin lymphoma
- chronic lymphocytic leukemia (CLL)
- Drugs: alpha-methyldopa, PCN, cephalosporins
148
HML Pathology:
How do you diagnose warm antibody hemolytic anemia? 2 points
- spherocytosis
- positive direct Coombs test
149
HML Pathology:
How do you treat warm antibody hemolytic anemia? 3 points
- drug cessation
- steroids
- splenectomy if necessary
150
HML Pathology:
Where is intravascular hemolysis seen in Cold Agglutinin IHA?
Distal body parts
151
HML Pathology:
How does extravascular hemolysis happen in Cold Agglutinin IHA?
IgM is released when the cells are warm, leaving C3b bound to the membrane
152
HML Pathology:
How does Cold Agglutinin IHA present? 5 points
- Episodic hyperbilirubinemia: hemoglobinemia and hemoglinuria
- positive Coombs test
- elevated C3
- Acute: in recovery phase after infectious Mononucleosis or mycoplasma pneumonia
- Chronic: associated with lymphoproliferative neoplasms; may be associated with Raynaud phenomenon due to vascular obstruction
153
HML Pathology:
How is cold agglutinin IHA treated? 3 points
- steroids
- IVIG
- plasmapheresis
154
HML Pathology:
What two settings can Erythroblastosis Fetales occur?
- Mother is Rh- gives birth to Rh+ baby
- ABO incompatibility: mother is type O and baby is type A or B
155
HML Pathology:
How does Erythroblastosis Fetalis present?
Fetal hemolytic anemia
156
HML Pathology:
How do you diagnose Erythoblastosis Fetalis?
Test maternal and fetal blood for presence of antibodies
157
HML Pathology:
What is the prognosis for Erythroblastosis fetalis? 3 points
- Stillbirth
- hydrops fetalis (fetal heart failure)
- kernicterus
158
HML Pathology:
What is kernicterus?
Unconjugated bilirubin damaging the basal ganglia and other CNS structures, leading to neurological damage
159
HML Pathology:
How do you prevent Erythroblastosis fetalis?
Treat mother with anti-D Ig (RhoGAM) during and after each pregnancy
160
HML Pathology:
How is Anemia of Chronic Disease characterized? 2 points
- marrow hypoproliferation as a result of impaired responsiveness to EPO
- impaired iron utilization
161
HML Pathology:
What are the common causes of Anemia of Chronic Disease? 4 points
- Chronic infections: Osteomyelitis and bacterial endocarditis, etc
- Chronic immune disorders: rheumatoid arthritis, SLE
- Renal disease
- Neoplasms: Hodgkin disease, lung carcinoma, etc
162
HML Pathology:
What are the mechanisms behind anemia of chronic disease? 2 points
- Increased hepcidin (produced from liver) limits iron release from macrophage to erythroid precursors and suppresses EPO release
- Increased hepcidin sequesters iron to keep it away from microorganisms
163
HML Physiology:
What is the role of Hepcidin?
Master regulator in iron metabolism, normally limits iron transport by binding to ferroportin (iron transporter present in intestinal mucosal cells and macrophages)
164
HML Pathology:
How does Anemia of chronic disease present?
Symptoms of the chronic disease along with mild anemia (fatigue, pallor)
165
HML Pathology:
How do you diagnose Anemia of chronic disease? 6 points
- decreased TIBC
- decreased serum iron
- increase serum ferritin (iron stores in macrophages
- nornocytic, normochromic RBCs in the early stage
- Microcytic and hypochromic RBCs in the late stage
- Decrease hemoglobin and hematocrit in CBC
166
HML Pathology:
How do you treat an anemia of chronic disease? 2 points
- administer EPO
- treat underlying condition
167
HML Pathology:
What are three ways an intrinsic hemolytic anemia can develop?
- complement fixation
- mechanical injury
- or toxins
168
HML Pathology:
What do you look for in an intravascular hemolytic anemia? 8 points
- hemoglobinemia, methemalbuminemia
- mild jaundice/ elevated unconjugated bilirubin
- hemoglobinuria (early stage)
- hemosiderinuria
methemoglobinuria
- decreased serum haptoglobin
- hemosiderosis of renal tubules (chronic stage)
- increased fecal urobilin
169
HML Pathology:
What causes an extravascular hemolytic anemia?
4 points
- Due to RBC injury
- antibody attachment
- structural or membrane defects leading to abnormal shape
- decreased ability to leave cords of Billroth (red pulp) and enter sinusoids of spleen
170
HML Pathology:
Where does hemolysis usually occur in extravascular hemolytic anemia?
Inside of mononuclear phagocytic cells in the spleen (RES)
171
HML Pathology:
What do you look for in extravascular hemolytic anemia? 4 points
- jaundice/ elevation in unconjugated bilirubin (increased risk of bilirubin gallstones_
- some decrease in haptoglobin
- Splenomegaly
- Minimal hemoglobinemia and hemoglobinuria
172
HML Pathology:
What are some hereditary circumstances that cause an intrinsic hemolytic anemia, that is categorized and intravascular and extravascular?
2 points
Enzyme deficiencies:
- HMP shunt: G6PD, glutathione synthetase
- Glycolytic enzymes: pyruvate kinase, hexokinase
173
HML Pathology:
What are some hereditary circumstances that cause an intrinsic hemolytic anemia, that is categorized as purely extravascular? 2 categories
Membrane disorders:
- elliptocytosis
- spherocytosis
Hemoglobin synthesis derangements:
- Thalassemias
- Sickle cell anemia (can also be Intravascular)
174
HML Pathology:
What are some acquired circumstances that cause an intrinsic hemolytic anemia, that is categorized as purely extravascular?
- membrane disorders (EV)
- Paroxysmal nocturnal hemoglobinuria
175
HML Pathology:
What are some acquired circumstances that cause an extrinsic hemolytic anemia, that is categorized as purely intravascular? 4 categories
Antibody mediated
- transfusions reactions, erythroblastosis fetalis, SLE, malignancies, mycoplasma infection, mononucleosis, drugs, idiopathic
Mechanical injury:
- MAHA: TTP (thrombotic thrombocytopenia purpura), DIC (disseminated intravascular coagulation
- Cardiac traumatic hemolytic anemia
Infections:
- Malaria, babesiosis
Chemical injury:
- lead poisoning
176
HML Pathology:
What are some acquired circumstances that cause an extrinsic hemolytic anemia, that is categorized as purely extravascular?
Hypersplenism
177
HML Pathology:
What is the pathogenesis of Sickle cells disease?
Point mutation (substitution of glutamic acid to valine at position 6) in the beta-chain gene leading to abnormal hemoglobin, HbS
178
HML Pathology:
Carriers of the sickle cell trait have protection against what?
Plasmodia falciparum malaria
179
HML Pathology:
Describe the sickle cell variant: Sickle cell trait: 5 points
- heterozygotes with an HbA and an HbS allele (HbSA)
- usually asymptomatic without anemia and only present with microscopic hematuria
- increased risk of renal microinfarctions and renal papillary necrosis
- labs positive for metabisulfate
- Hb electrophoresis shows 55% HbA, 43% HbS, 2% HbA2
180
HML Pathology:
Describe the sickle cell variant: Sickle cell disease
Homozygotes have two HbS alleles (HbSS)
181
HML Pathology:
Describe the sickle cell variant: HbSC
Heterozygotes with an HbS and HbC (glutamic acid to lysine substitution allele
182
HML Pathology:
What is the order of severity of the different sickle cell variants?
HbSS > HbSC > HbSA
183
HML Pathology:
Describe the sickle cell variant: Sickle Beta-Thalassemia
Heterozygotes with an HbS and Beta-thalassemia (HbS/[beta]Th)
184
HML Pathology:
What causes the sickle cell shape?
Aggregation and polymerization of HbS when deoxygenated
- hypoxia and fall in pH can also cause sickling
185
HML Pathology:
What is a consequence of the sickle cell shape?
- subject to splenic destruction
- makes the blood hyper viscous which can lead to microvascular occlusion
186
HML Pathology:
What can cause the MCHC to increase?
Dehydration
187
HML Pathology:
What prevents polymerization of HbS in a newborn before 6 months?
HbF
188
HML Pathology:
What are the four different groups of symptoms a patient with sickle cell can have?
Mneumonic: SHAVe
1. Vasoocclusion symptoms
2. Sequestration symptoms
3. Hemolytic symptoms
4. Aplastic symtoms
189
HML Pathology:
How do the vaso-occlusion symptoms present in sickle cell disease? 8 points
- pallor
- Strokes
- acute chest syndrome (associated with fever, hypoxia, and pulmonary infiltrate)
- Dactylics
- Aseptic necrosis of femoral or humeral head
- Pain episodes in joints, abdomen, viscera, lung, liver, and penis
- increased susceptibility to encapsulated bacteria including Salmonella osteomyelitis secondary to asplenia
- Renal papillary necrosis, which leads to gross hematuria and proteinuria
190
HML Pathology:
How do the sequestration symptoms present in sickle cell disease? 2 points
- acute pooling of erythrocytes in the spleen after encapsulated infection
- acute splenomegaly and septic shock-like state and hypovolemia
191
HML Pathology:
How do the Hemolytic symptoms symptoms present in sickle cell disease? 2 points
- intravascular hemolysis
- massive erythroid hyperplasia due to expansion of hematopoiesis into skull ("crewcut"), facial bone ("chipmunk face"), and extra medullary hematopoiesis with hepatomegaly
192
HML Pathology:
How do the aplastic symptoms present in sickle cell disease?
increase risk of Parvovirus B19 infection
193
HML Pathology:
How do you diagnose sickle disease? 6 points
- Hb Electrophoresis
- Metabisulfate screen: Positive in both sickle cell trait and disease
- CBC: anemia, reticulosytosis, leukocytosis, thrombocytosis
- PBS: Sickled cells and Howell-Jolly Bodies (basophilic nuclear remnants due to autosplenectomy)
- serum bilirubin and fecal/urinary urobilinogen are elevated (dues to extravascular hemolysis; low haptoglobin level (due to intravascular hemolysis)
- skull radiograph shows "crew cut" pattern due to extramedulary hematopoiesis
194
HML Pathology:
How do you treat sickle cell disease?
- hydration
- folic acid supplementation
- blood transfustion
- PCN prophylaxis
- Vaccination against pneumococcal, H influenza, and meningococcal
- pain control
- Bone marrow transplantation
- Hydroxyurea (increases concentration of HbF
195
HML Pathology:
What is the inheritance pattern of pyruvate kinase deficiency?
Autosomal recessive
196
HML Pathology:
How does a chronic anemia occur in the setting of Pyruvate Kinase deficiency? 2 points
- chronic decreased ATP, leading to membrane damage because the Na+/K+ ATPase cannot be maintained
- there is also a buildup of 2,3-BPG inducing a right shift, promoting oxygen unloading in the peripheral tissue
197
HML Pathology:
How does a Pyruvate Kinase Deficiency present? 3 points
- neonatal jaundice
- extravascular hemolysis
- splenomegaly
198
HML Pathology:
What gene is mutated in Paroxysmal Nocturnal Hemoglobinuria?
What does it lead to pathophysiologically?
(Total 3 points)
- PIGA
- synthesis of glycosylphosphatidylinositol (GPI) anchors used for surface anchor protein attachment
- without GPI no inactivation of complement, subjecting RBCs to lyse by endogenous compliment, platelets and granulocytes can be affected also
199
HML Pathology:
How does Paroxysmal Nocturnal Hemoglobinuria (PNH) present?
5 points
- episodic hemoglobinuria on awakening (mild respiratory acidosis from shallow breathing at sleep increases CO2 and activates complement)
- hemosiderinuria can lead to iron deficiency
- Pancytopenia (cell lysis)
- Increased risk of venous thrombosis
- increased risk for acute myeloid leukemia
200
HML Pathology:
How would diagnose PNH? 3 points
- clinical presentation
- flow cytometry to detect lack of CD55 decay-accelerating factor (DAF) on blood cells
- sucrose test or acidified serum test (activates complement)
201
HML Pathology:
What is the prognosis of PNH?
- aplastic anemia
- acute leukemia
202
HML Pharmacology:
How would you treat PNH?
Eculizumab and Ravulizumab (terminal compliment inhibitor)
203
HML Pathology:
What is Microangiopathic Hemolytic Anemia?
Mechanical trauma caused buy narrowed vessels leading to intravascular hemolysis
204
HML Pathology:
What conditions would you see a Microangiopathic Hemolytic Anemia? 7 points
- Disseminated intravascular coagulation (DIC)
- thrombotic thrombocytopenic purpura (TTP
- hemolytic-uremic syndrome (HUS)
- SLE
- malignant HTN
- prosthetic heart valves
- aortic stenosis
205
HML Pathology:
How would you diagnose microangiopathic hemolytic anemia?
PBS: schistocytes
206
HML Pathology:
What is the cause of cardiac traumatic hemolytic anemia?
Turbulent flow and abnormal pressures occurring is prosthetic heart valves
207
HML Pathology:
What is underlying problem in Aplastic Anemia?
Failure or destruction of multipotent myeloid stem cells leads to inadequate production or release of differentiated cell lines
208
HML Pathology:
What some common causes of Aplastic Anemia? 6 points
- chemicals: Benzene
- Drugs: CHloramphenicol, sulfonamides, alkylating agents, antimalarial drugs, antimetabolites
- Fanconi anemia
- Idiopathic (immune-mediated or primary stem cell defect
- radiation
- Viral agents: Parvovirus B19, EBV, HIV, hepatitis C Virus
209
HML Pathology:
How does aplastic anemia present?
Onset is gradual
- anemia
- thrombocytopenia
- neutropenia
210
HML Pathology:
How is an aplastic anemia diagnosed?
- CBC
- Marrow biopsy: Hypocellular bone marrow and fatty infiltration
- Peripheral smear: pancytopenia
*no reticulocytosis and no splenomegaly
211
HML Pathology:
What is the treatment for an aplastic anemia? 5 points
- withdrawal of offending agent
- immune therapy: antithymocyte globulin, cyclosporine
- allogenic bone marrow transplantation
- RBC and platelet transfusion
- Granulocyte colony-stimulating factor (G-CSF), granulocyte- macrophage colony-stimulating factor (GM-CSF)
212
HML Pathology:
What is the prognosis of aplastic anemia?
Unless it's idiopathic, withdrawal of offending agent may lead to recovery
213
HML Pharmacology:
What is common adverse effect of chloramphenicol?
Aplastic anemia
214
HML Pathology:
What can porphyria be defined as?
A group of diseases that result from the accumulation of heme intermediates
215
HML Pathology:
What is the inheritance patter of acute intermittent porphyria?
Autosomal dominant
216
HML Pathology:
What enzyme is deficient in AIP?
Porpholbilinogen deaminase
217
HML Pathology:
What is accumulated in acute intermittent porphyria? What does it lead to? 2 points
- Porphobilinogen
- leads to degeneration of myelin
218
HML Pathology:
How does AIP present? 6 points
- medication induced (anything that increases heme synthesis: sulfa drugs, barbiturates, P450 inducers
Symptoms:
- dark, foul-smelling urine
- abdominal pain
- hallucinations
- blurred vision
- peripheral motor neuropathy (eg, foot drop) MIMICING GBS
219
HML Pathology:
How would you diagnose AIP? 3 points
- Genetic testing
- increased urinary secretion of porphobilinogen and porphyrins
- no sun-induced lesions
220
HML Pathology:
How would treat AIP? 2 points
Goal is to decrease heme synthesis to reduce porphyrin precursor production
- high-carb diet during attacks
- severe attacks should be treated with hematin (inhibits ALA synthase)
221
HML Pathology:
What enzyme has deficient activity in Porphyria Cutanea Tarda?
Urophorphyrinogen decarboxylase (UROD)
222
HML Pathology:
What is elevated in Porphyria Cutanea Tarda?
Memory Aid: PCT increases your chances of getting a UTI
- Uroporyphyrin (large, insoluble molecule and photosensitive)
- Iron
- Transferrin
223
HML Pathology:
How does Porphyria Cutanea Tarda present? 5 points
- Cutaneous bullous
- skin lesions that form after sun exposure
- organ damage from siderosis affecting the liver progressing to fibrosis
- urine turns dark upon standing
- disease exacerbates by consuming of alcohol, iron, and estrogens
**uroporphyrinogen decarboxylase (UROD) defeciency, which is a key enzyme in the heme biosynthesis pathway
224
HML Pathology:
How is Porphyria Cutanea Tarda diagnosed?
Plasma and urine analysis for elevated uroporphyrin (RBC's can also be tested too)
225
HML Pathology:
How is Porphyria Cutanea Tarda treated? 3 points
- low dose antimalarial medications
- phlebotomy
- avoid alcohol, sun exposure, estrogens, and iron
226
HML Pathology:
What is a consequence of severe thrombocytopenia?
Life-threatening intracranial bleeding
227
HML Physiology:
What does von Willobrand Factor bind to?
collagen
228
HML Physiology:
What releases von Willowbrand factor?
- Weibel-Palade bodies of endothelial cells
- alpha granules of platelets
229
HML Pathology:
What labs would you expect in a pt with vessel abnormalities? 5 points
- Normal platelet count
- increase bleeding time
- normal PT
- normal PTT
- normal thrombin time/ fibrinogen
230
HML Pathology:
What labs would you expect in a pt with thrombocytopenia? 5 points
- decreased platelet count
- increased bleeding time
- normal PT
- normal PTT
- normal thrombin time/ Fibrinogen
231
HML Pathology:
What labs would you expect in a pt with qualitative platelet defects? 5 points
- normal platelet count
- increased bleeding time
- Normal PT
- normal PTT
- normal thrombin time/ fibrinogen
232
HML Pathology:
What labs would you expect in a pt with Hemophilia A or B?
- normal platelet count
- normal bleeding time
- normal PT
- increased PTT
- normal thrombin time/ fibrinogen
233
HML Pathology:
What labs would you expect in a pt with vitamin K deficiency?
- normal platelet count
- normal bleeding time
- increased PT
- increased PTT
- normal thrombin time/ fibrinogen
234
HML Pathology:
What labs would you expect in a pt with von Willebrand disease?
- normal platelet count
- increased bleeding time
- normal PT
- normal/increased PTT
- normal thrombin time/ fibrinogen
235
HML Pathology:
What labs would you expect in a pt with DIC?
- decrease platelet count
- increased bleeding time
- increased PT
- increased PTT
- increased thrombin time/ fibrinogen
236
HML Pathology:
What labs would you expect in a pt with Liver disease?
- decreased platelet count
- increased bleeding time
- increased PT
- increased PTT
- increased thrombin time/fibrinogen
237
HML Pathology:
What labs would you expect in a pt with multiple transfusions?
- decreased platelet count
- increased bleeding time
- increased PT
- increased PTT
- increased thrombin time/ fibrinogen
238
HML Pathology:
What is the treatment for Idiopathic thrombocytopenia purpura?
- Initial treatment is corticosteroids
- IVIG for symptomatic bleeding
- splenectomy for refractory cases
239
HML Pathology:
How does thrombotic microangiopathies occur?
Result from hyaline micro thrombi (platelet aggregates surrounded by fibrin) leading to thrombocytopenia and MAHA.
240
HML Physiology:
what is a normal bleeding time?
2 to 9 minutes
241
HML Pathology:
What causes a prolonged PT (prothrombin) time?
Deficiency in factors V, VII, or X, prothrombin, or fibrinogen
242
HML Pathology:
What causes a prolonged PTT (Partial thromboplastin time)?
Heparin therapy
243
HML Pathology:
What enzyme is lacking in Thrombotic Thrombocytopenia Purpura (TTP)?
metalloproteinase ADAMTS13
244
HML Pathology:
What symptoms does TTP portray?
5 points
- Microangiopathic hemolytic anemia
- thrombocytopenia
- renal failure
- fever
- neurological symptoms
245
HML Pathology:
What population would you see TTP?
Adult females
246
HML Pathology:
What platelet count would you consider to be pathological?
under 100,000
247
HML Pathology:
What platelet count would you consider a patient to have spontaneous bleeding?
under 20,000
248
HML Pathology:
What is the only lab value that is decreased in DIC?
Platelet count
249
HML Pathology:
What is the inheritance of von Willebrand disease?
Autosomal dominant
250
HML Physiology:
What is the role of von Willebrand Factor?
Carry and stabilize factor 8
251
HML Pathology:
What is the inheritance pattern of Bernard-Soulier disease?
Autosomal recessive
252
HML Pathology:
What is the problem inBernard- Soulier disease?
platelets are abnormally large and lack platelet-surface glycoprotein IB, leading to defective platelet adhesion
253
HML Physiology:
What is the product of cyclooxygenase?
Thromboxane A2, a platelet aggregate
254
HML Pathology:
What is deficient in Glanzmann thrombasthenia?
glycoprotein IIB and IIIA, required for forming fibrinogen bridges between platelets during platelet aggregation
255
HML Pathology:
What is the inheritance in classic hemophilia?
X-linked deficiency of factor VIII (hemophilia A)
256
HML Pathology:
What lab change would you expect in classic hemophilia?
PTT normalizes in mixing studies
257
HML Pathology:
How do you treat classic hemophilia?
Factor VIII and Desmopressin to release additional Factor VIII from the endothelial stores
258
HML Pathology:
What is the problem in Christmas Disease?
X linked deficiency of factor IX, mixing studies does not correct after factor VIII
259
HML Pathology:
What is the inheritance and problem in Hemophilia C?
Autosomal Recessive deficiency of factor XI affecting PTT
260
HML Pathology:
What vitamin is absent in breastmilk?
Vitamin K
261
HML Physiology:
What enzyme activate vitamin K?
Epoxide reductase
262
HML Pathology:
What kind of symptoms would you see in Liver disease? 3 points
- hemarthroses (bleeding into joints)
- easy bruising
- hematomas rather than petechiae
263
HML Pathology:
What components are 'consumed' in disseminated intravascular coagulation DIC? 2 points
- platelets
- coagulation factors (II, V, VIII, Fibrinogen)
264
HML Pathology:
Describe the mechanism that causes DIC? 2 points
- release of tissue thromboplastin, or
- activation of the intrinsic pathway
265
HML Pathology:
What are the common causes of DIC? 7 points
- obstetric complication
- gram negative sepsis
- transfusion, trauma
- malignancy ( esp. adenocarcinoma of the lung, pancreas, prostate, and stomach)
- acute pancreatitis
- nephritic syndrome
- acute promyelocytic leukemia (degranulation)
266
HML Pathology:
What risk is increased with Ehlers-Danlos syndrome?
- aortic dissection and berry aneurysm
267
HML Pathology:
What is the cause of vessel wall abnormalities in Cushing Syndrome?
Protein wasting
268
HML Pathology:
What kind of vessel wall abnormalities are associated with Henoch-Schönlein purpura?
- Hypersensitivity vasculitis, often associated with URI.
- Symptoms include palpable purpura, polyarthraligias, fever, painful focal GI hemorrhages, and acute glomerulonephritis
269
HML Pathology:
What is the inheritance pattern of Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)?
Autosomal dominant
270
HML Pathology:
Why does Waldenström macroglobinulinemia cause vessel wall abnormalities?
Hyperviscous blood
271
HML Pathology:
What test has replaced bleeding time tests?
Platelet function assay (PFA)-100
272
HML Pathology:
How does hypercortisolism create eosinopenia?
Sequesters eosinophils inside of lymph nodes
273
HML Pathology:
What causes a neutrophilic leukocytosis? 2 points
- Bacterial infection
- tissue necrosis
274
HML Pathology:
What number is considered a lymphopenia? 2 points
- < 1500 in adults
- < 3000 in children
275
HML Pathology:
What number is considered leukocytosis? 2 points
- > 4000 in adults
- > 8000 in children
276
HML Pathology:
What are 5 key facts about Hodgkin lymphomas?
- Reed-Sternberg cells (CD15 CD30)
- single groups of axial nodes
- contiguous spread
- constitutional symptoms
- bimodal distribution
277
HML Pathology:
What are the four histological variants of Hodgkin lymphoma?
- nodular sclerosis
- mixed cellularity
- lymphocyte predominant
- lymphocyte depleted
278
HML Pathology:
What viral infection is commonly associated with Hodgkins Lymphoma?
EBV
279
HML Pathology:
What are six key facts about non-hodgkin lymphomas?
- No Reed-Sternberg cells
- multiple groups of peripheral nodes
- noncontiguous spread
- fewer constitutional symptoms
- usually seen in those 2--40 years old
- associated with HIV and autoimmune diseases
280
HML Pathology:
What is the translocation for CML?
t(9;22) Ph chromosome
281
HML Pathology:
What is the translocation for Burkitt lymphoma?
t(8;14) c-myc
282
HML Pathology:
What is the translocation for Follicular lymphoma?
t(14;18) bcl-2
283
HML Pathology:
What is the translocation for AML M3 type?
t(15;17) APL: RARA
284
HML Pathology:
What is the translocation for Ewing Sarcoma?
t(11;22)
285
HML Pathology:
What is the translocation for Mantle cell lymphoma?
t(11;14)
286
HML Pathology:
What determines the prognosis of Hodgkin Lymphomas?
3 points
- Staging, the best predictor of prognosis.
- Amount of lymphoid aggregates and dissemination.
- Also chemotherapy and radiation therapy can induce secondary cancers.
287
HML Physiology:
What three actions does Bradykinin do?
Increase vasodilation, permeability, and pain
288
HML Pathology:
What type of non-hodgkin lymphoma is the only nodular type?
Follicular Lymphoma
289
HML Pathology:
Describe Hodgkin Lymphoma type: Nodular Sclerosing (7 points)
- Women > Men
- Cells grouped into nodule surrounded by "fibrous bands"
- usually located in cervical, supraclavicular, or mediastinal nodes
- Lacunar cells (Reed-Sternberg nucleus surrounded by empty space
- can be related to EBV infection
- Most common prevalence (70%)
- Excellent prognosis
290
HML Pathology:
Describe histology of Hodgkin Lymphoma: Mixed cellularity (7 points)
- typically seen in young men
- also often related to EBV infection
- complete effacement, multiple nodes
- Eosinophils, plasma cells, histiocytes, and Reed-Sternberg cells with regions of fibrosis
- 2nd most common (25%)
- most amount of Reed-Sternberg cells
- intermediate prognosis
291
HML Pathology:
Describe histology of Hodgkin Lymphoma: Lymphocyte predominant (6 points)
- Lymphocytes and histiocytes
- <35 year old men
- popcorn cells (Reed-Sternberg cells)
- 6% prevalence
- most amount of lymphocytes involved
- excellent prognosis
292
HML Pathology:
Describe histology of Hodgkin Lymphoma: Lymphocyte depleted (6 points)
- few lymphocytes with large number of Reed-Sternberg cells and fibrosis
- older men with disseminated disease, HIV patients
- most rare prevalence
- Higher number of RS cells relative to lymphocytes
- Least amount of lymphocytes involved
- poor prognosis
293
HML Pathology:
In terms of Cutaneous T-cell Lymphomas, what is the difference between Mycosis fungoides and Sézary syndrome?
Mycosis fungoides is in the skin (dermis and epidermis), Sézary syndrome is in the blood
294
HML Pathology:
How would you diagnose Cutaneous T-cell Lymphoma? 2 points
- Bx showing CD4+ T cells with cerebriform nuclei proliferating in the dermis
- focal concentrations of neoplastic cells in the epidermis are called Pautrier microabscesses
295
HML Pathology:
Describe the prognosis of Cutaneous T-cell lymphomas? 3 points
- indolent (minimal pain)
- average survival 8-9 years
- can progress to diffuse large-cell lymphoma
296
HML Pathology:
What organs/structures are affected in a MALToma? 4 points
- Salivary glands
- Small intestines
- Large intestines
- Lungs
297
HML Pathology:
What bacterial infection is associated with MALToma?
Helicobacter Pylori
298
HML Pathology:
What common chronic inflammatory conditions are associated with MALTomas? 2 points
- Hashimoto Thyroiditis
- Sjögren syndrome
299
HML Pathology:
Describe the histological type and its characteristics of Non-Hodgkin lymphoma: Small lymphocytic lymphoma
5 points
- Histology: Small, mature looking lymphocytes; lymph nodes are effaced
- affects B cells in adults
- low grade
- appears as a focal mall of CLL
- "Richter syndrome" or prolymyphocytic transformation into diffuse B-cell lymphoma occurs in a quarter of cases
300
HML Pathology:
Describe the histological type and its characteristics of Non-Hodgkin lymphoma: Follicular lymphoma
8 points
- Histology: arranged in nodules
- complication include progression to diffuse large B-cell lymphoma
- Genetics: t(14;18), BCL2 to Ig Heavy chain locus on chromosome 12 leads to over expression and prevents apoptosis (bad thing in this case)
- Low grade
- B cells affected
- affects adults
- Presentation is painless "waxing and waning" lymphadenopathy
- Tx is low dose chemotherapy or rituximab
301
HML Pathology:
Describe the histological type and its characteristics of Non-Hodgkin lymphoma: Diffuse Large cell
8 points
- Histology: Large B cells that grow diffusely in sheets
- Genetics: associated with BCL-6
- intermediate grade
- 80% B cells, 20% mature T cells involved
- 80/20 % split for adult and children involved
- occurs most commonly
- often presents with extra nodal mass
- aggressive, 50% cure rate
302
HML Pathology:
Describe the histological type and its characteristics of Non-Hodgkin lymphoma: Mantle cells lymphoma
6 points
- Histology: resemble cells in the mantle zone of lymph nodes
- Genetics: t(11'14) - cyclin D1 (11) and Ig heavy chain (14) leads to over expression of cyclin D1, which promotes G1/S transition
- B cells affected
- adults affected
- poor prognosis
- GI tract often involved causing lymphomatoid polyposis
303
HML Pathology:
Describe the histological type and its characteristics of Non-Hodgkin lymphoma: Lymphoblastic lymphoma
7 points
- Histology: cell nuclei appear convoluted (twisted); arise from thymic lymphocytes
- High grade
- Immature T cells involved most commonly in children but adults too
- 80% cure rate, but high relapse rate
- presents with ALL and mediastinal mass
304
HML Pathology:
Describe the histological type and its characteristics of Non-Hodgkin lymphoma: Burkitt Lymphoma
9 points
- Histology: starry-sky appearance (sheets of lymphocytes with interspersed nonneoplastic macrophages), high mitotic index
- Genetics: t(8;14) - translocation of c-myc (8) and Ig Heavy chain.
- High grade
- B cells affected
- children and adults affected
- associated with EBV, HPV
- very rapid growing mass
- jaw involved common in endemic affray form
- pelvic/abdomoninal involvement often occurs in sporadic form
305
HML Pathology:
Where can you expect for relapses to occur in acute lymphoblastic leukemia?
CNS and testes
306
HML Pathology:
How does acute lymphoblastic leukemia present?
2 points
- adolescent with a mediastinal mass that may spread other trachea, esophagus, and SVC
- Marrow failure, lymphadenopathy, splenomegaly hepatomegaly also important findings
307
HML Pathology:
What are the common leukemias pertaining to ages <15, 15-39, >40-60, and 60+ years respectively?
4 points
- < 15 yrs: ALL
- 15-39 yrs: AML
- >40-60 yrs: AML, CML
- 60+: CLL
308
HML Pathology:
What tests would you order to diagnose a leukemia?
3-4 points
- Flow cytometry
- PBS
- bone marrow biopsy
Would see monomorphic cels with condensed chromatin, minimal cytoplasm, and no granules
309
HML Pathology:
How can you differentiate an Acute myeloid leukemia from T cell and B cell?
- Surface markers
TdT+ marks for pre-T and pre-B; CD10+ is a marker for pre-B only.
310
HML Pathology:
What is often associated with acute lymphoblastic leukemia?
What labs would you expect to see?
2 points
- Tumor lysis syndrome
- hyperuricacidemia, hyperphosphatemia, hyperkalemia
311
HML Pathology:
What cell marker would you expect to see in Chromic Lymphocytic Leukemia?
CD5+ B cells
312
HML Pathology:
Do the proliferating B cells mature to plasma cells and secrete antibodies in CLL?
No
313
HML Pathology:
How does chronic lymphocytic leukemia present?
5 points
- 60 yr old pts or older
- lymphadenopathy and hepatosplenomegaly are common
- bacterial infection common due to hypogammaglobunemia
- auto bodies can form and cause warm antibody autoimmune hemolytic anemia or thrombocytopenia
- prolymphocytic transformation into diffuse B-cell lymphoma occurs in 25% of cases (Richter transformation)
314
HML Pathology:
How can you diagnose CLL?
2 points
- Peripheral smears and bone marrow bx will show smudge cells
- some pts may show a monoclonal Ig "spike"
315
HML Pathology:
What is another name for Acute myelogenous Leukemia (AML)?
Acute granulocytic leukemia
316
HML Pathology:
What is the pathophysiology of APML?
2 points
- Translocation of the retinoid acid receptor-alpha gene from chromosome 17 to the promyelocytic leukemia gene on chromosome 15
- t(15;17)(q22;q12) - prevents cell differentiation and maturation
317
HML Pathology:
What age population would you expect AML to come from myelodysplasia?
60+ yr
318
HML Pathology:
What symptoms does AML present with?
4 points
- fatigue
- infection
- bleeding (anemic, neutropenia, thrombocytopenia)
- cutaneous lesions (leukemia cutis, gingival hypertrophy, and chloromas)
319
HML Pathology:
What are some risk factors for AML?
4 points
- Hx of alkylating agents
- hx of topoisomerase inhibitors
- radiation
- myeloproliferative disorders
320
HML Pathology:
How would you diagnose AML?
6 points
- peripheral smeal
- bone marrow biopsy
- biopsy reveals >20% myeloid blasts in marrow
- myeloblasts will be peroxidase-positive and have abundant cytoplasm compared with lymphoblasts
- Aeur rods present (peroxidase positive cytoplasmic inclusions)
- The lack of TdT and CD10 surface markers to differentiate from ALL
321
HML Pathology:
How can you compare CLL and SLL (small)?
same except CLL proliferates in the blood and BM vs SLL in the nodal and extra nodal masses
322
HML Pharmacology:
How do you treat AML?
2 points
- chemotherapy:
7 + 3 + 3 - cytarabine, daunorubicin, etoposide
- high dose all- trans retinoid acid for APML (APL) with t(15;17)
323
HML Pharmacology:
What is the danger in treating APL?
Tx can release large numbers of Auer rods, which can result in DIC
324
HML Pathology:
Which leukemia is also a myeloproliferative disorder?
Chronic Myelogenous Leukemia
325
HML Pathology:
What is the pathophysiology of Chronic Myelogenous Leukemia?
Translocation 9;22 cause BCR-ABL fusion, this has tyrosine kinase activity which enhances cellular proliferation, inhibiting normal cell production due to overcrowding. Associated with the Ph (Philadelphia) chromosome.
326
HML Pathology:
Describe the how CML presents?
4 points
- insidious onset with nonspecific symptoms
- splenomegaly is common
- accelerated phase with increasing anemia and thrombocytopenia occurring after around 3 years
- all untreated pts eventually enter a blast crisis with > 20% blasts. 2/3 progress to AML, 1/3 ALL
327
HML Pathology:
What are the risk factors for developing Chronic Myelogenous Leukemia?
2 points
- ionizing radiation
- Benzene
328
HML Pathology:
How can you diagnose CML?
3 points
- chromosomal analysis or PCR to detect BCR-ABL fusion gene
- Bone marrowy biopsy and peripheral smear also show leukocytosis with mixed neutrophils, metamyelocytes, and absolute basophilia
- normal leukocyte ALP is no elevated (vs leukemoid reaction)
329
HML Pharmacology:
How do you treat chronic myelogenous leukemia?
2 points
- Gleevec (imatinib mesylate, a small- molecule inhibitor of the BCR-ABL tyrosine kinase): induces apoptosis of leukemic cells
- Allogenic bone marrow transplantation: cures 75%, most effective in the stable phase
330
HML Pathology:
Which leukemia has cells that are CD103+ and TRAP+ (tartrate resistant acid phosphatase)?
Hairy cell leukemia
331
HML Pathology:
What can Hairy cell leukemia progress to?
Marrow fibrosis, bone marrow bx will show "dry tap"
332
HML Pathology:
How do you treat Hairy cell leukemia?
2 points
- Cladribine
- adenosine deaminase inhibitor
333
HML Pathology:
How is Adult T-cell Leukemia/Lymphoma caused?
- infection with a retrovirus HTLV-1 (human T-cell leukemia virus type 1)
334
HML Pathology:
How is Adult T-cell leukemia/lymphoma characterized?
5 points
- skin lesions
- generalized lymphadenopathy
- HS-megaly
- hypercalcemia
- elevated leukocyte count with multi lobed CD4 lymphocytes
335
HML Pathology:
What can hairy cell leukemia progress to?
Demyelination of the CNS
336
HML Pathology:
How many Plasma Cell disorders are there?
Name them
3
- Multiple myeloma
- Waldenström macroglobulinemia
- Monoclonal gammopathy
337
HML Pathology:
What is the M component?
Monoclonal Ig
338
HML Pathology:
Why are Bence Jones proteins made?
There is a loss of balance between the heavy and light chains, causing excess free light chains to escape in the urine.
339
HML Pathology:
Who is responsible for the myeloma proliferation and its survival in Multiple Myeloma?
IL- 6
340
HML Pathology:
What is the mnemonic for the clinical manifestations in Multiple Myeloma?
Name each component
CRAB
- hyperCalcemia
- Renal involvement
- Anemia
- Bone lytic lesions/ Back pain
341
HML Pathology:
How does multiple myeloma present?
8 points
- 50-60 yr
- punched out bone lesion in vertebrae or skull (osteoclast activating factor, IL-1 on RANK receptors)
- Hypercalcemia
- myeloma kidney, or renal insufficiency with azotemia. Bence Jones proteins can cause tubular casts
- Marrow failure (anemia > leuko/thrombocytopenia
- Infections (Staph A, Strep Pneumonia, E. coli)
- Amyloidosis from IgG light chain
- Hyperviscosity syndrome (rare)
342
HML Pathology:
How can you diagnose Multiple Myeloma?
6 points
- rouleaux formation of RBCs
- Electrophoresis reveal increase Ig in blood
- Bence Jones proteins in the urine
- M spike: IgG 50% of the time, IgA 25% of the time
- punched out round skeletal lesions
- cells have a "fried egg" appearance
343
HML Pathology:
How can you treat Multiple Myeloma?
3 points
- Chemotherapy (remission in 50%)
- Bisphosponates
- Bone marrow transplant (improve survival but not curative)
344
HML Pathology:
What is Waldenström Macroglobulinemia?
Neoplasm of plasmacytoid lymphocytes (cells between B lymphocytes and plasma cells in terms of maturity) with monoclonal IgM secretion
345
HML Pathology:
How does Waldenström Macroglobulinemia present?
5 points
- affects older individuals
- nonspecific symptoms (fatigue and weight loss) are common
- lymphadenopathy, hepatomegaly, and splenomegaly
- anemia due to marrow failure and IgM cold antibody AI hemolysis
- hypervisocity syndrome presenting as visual impairment via retinal vascular dilation, neurological issues, bleeding, and Raynaud phenomenon
346
HML Pathology:
How can you diagnose Waldenström Macroglobulinemia?
- Serum electrophoresis reveals clonal IgM spike
- 10% of cases show Bence Jones proteinuria
- no bone lesions
347
HML Pathology:
What is the prognosis of Waldenström Macroglobulinemia?
2 points
- incurable and progressive, median survival of 4 years. Plasmapheresis for hemolysis and hyperviscosity syndrome.
- Rarely transforms to large-cell lymphoma
348
HML Pathology:
Describe MGUS:
4 points
- Monoclonal Gammopathy of Uncertain Significance
- Mostly benign M proteins, asymptomatic
- some can develop into multiple myeloma or other plasma cell pathologies after a decade
- Amyloidosis can also develop
349
HML Pathology:
How many different forms are there of Langerhans Cell Histiocytosis?
Name them:
Four
1. Letterer-Siwe disease
2. Hand-Schüller-Christian disease
3. Multifocal Langerhans cell histocytosis
4. Eosinophilic granuloma
350
HML Pathology:
Describe Letterer-Siwe disease:
6 points
- before 2 yrs of age
- acute disseminated histiocytosis
- cutaneous lesions on trunk and scalp
- marrow failure
- hepatosplenomegaly
- osteolytic lesions
351
HML Pathology:
Describe Hand-Schüller-CHristian disease:
Triad of calvarial lesions, DI, and exophthalmos
352
HML Pathology:
Describe Langerhans cell histocytosis:
6 points
- affects children
- fever
- eruptions on the scalp and ear canals
-recurrent infections
- HS-megaly
- DI from posterior pituitary involvement
353
HML Pathology:
Describe an Eosinophilic Granuloma:
- Unifocal or multifocal expansion of Langerhans cell, usually in the marrow space and occasionally in lung
- asymptomatic and benign
- may present with fracture in adolescence (without skin involvement)
- bx shows lagerhands cell with increased eosinophils and mixed inflammatory cells
354
HML Pathology:
How would you diagnose Langerhans Cell Histiocytosis?
Electron microscopy reveals Birbeck granules (CD1a and S-100 positive) in the cytoplasm, which appear like tennis rackets
355
HML Pathology:
What are the different kinds of myeloproliferative syndromes?
- Chronic Myelogenous Leukemia
- Polycythemia vera
- essential thrombocythemia
356
HML Pathology:
What cells do you expect to produce in excess in Polycythemia vera?
3 points
- Erythrocytes
- Granulocytes
- megakaryocytes
357
HML Pathology:
How does Polycythemia Vera present?
8 points
- insidious consent around 60 yrs
- cyanosis
- bleeding and thrombosis risks can lead to a DVT, MI, stroke, Budd-Chiari syndrome, splenic and mesenteric infarction
- headache
- pruritus after hot shower due to increase basophils
- "spent phase" showing BM fibrosis, resulting in extra medullary hematopoiesis
- Myelofibrosis with myeloid metaplasia
- Splenomegali
358
HML Pathology:
How do you diagnose Polycythemia Vera?
- increased hematocrit
- decreased EPO (JAK2 V617F mutation)
- bone marrow is hyper cellular until the spent phase
- Leukocyte ALP are elevated
359
HML Pathology:
How do you treat Polycythemia vera?
Phlebotomy; increased survival up to 10 years
360
HML Pathology:
Describe how relative polycythemia/erythrocythemia develops:
Due to decreased plasma volume (volume contraction) cause by H20 deprivation
361
HML Pathology:
Describe how absolute polycythemia/erythrocythrmia develops:
Increased total RBC mass due to PCV, increased sensitivity to EPO receptor, increased levels of EPO, physiologic changes, or EPO secreting tumors
362
HML Pathology:
Describe the plasma volume, RBC mass, SAO2, a EPO levels in Relative polycythemia/erythrocythemia:
- decreased Plasma volume
- no chance in RBC mass, SAO2, and EPO levels
363
HML Pathology:
Describe the plasma volume, RBC mass, SAO2, a EPO levels in Absolute polycythemia erythrocythemia?
- increase in plasma volume
- increase in RBC mass
- no change in SAO2
- decrease EPO levels
364
HML Pathology:
Describe the plasma volume, RBC mass, SAO2, a EPO levels in Hypoxia:
- no change in plasma volume
- increase in RBC mass
- decrease in SAO2
- increase in EPO levels
365
HML Pathology:
Describe the plasma volume, RBC mass, SAO2, a EPO levels in RCC (with ectopic EPO secretion:
- no change in plasma volume
- increase in RBC mass
- no change in SAO2
- increase in EPO levels
366
HML Pathology:
What is the prognosis of Polycythemia Vera?
Death within months without treatment
367
HML Pathology:
Describe the pathogenesis of Myelofibrosis with Myeloid Metaplasia:
Meoplastic changes in multipoint stem cells leading to. proliferation of megakaryocytes. Megakaryocytes release platelet-derived growth factor and transforming growth factor beta, which grows fibroblasts. Fibroblasts release lot of collagen leading to fibrosis. Similar to the spent stage in PCV.
368
HML Pathology:
How does Myelofibrosis with Myeloid Metaplasia present?
4 points
- 60+ yr
- anemia, bleeding, thrombosis, and recurrent infections
- hyperuricemia
- hepatosplenomegaly
369
HML Pathology:
How would you diagnose Myelofibrosis with Myeloid Metaplasia?
3 points
- Peripheral smear shows leukoerythroblastosis, increased numbers of nucleated erythroid progenitors and early granulocytes
- Dacrocytes/ teardrop erythrocytes
- normochromic normocytic anemia and thrombocytopenia as the disease advances
370
HML Pharmacology:
How would you treat myrlofibrosis with myeloid metaplasia?
JAK2 kinase inhibitors
371
HML Pathology:
How does Essential Thrombocythemia present?
Indolent course, usually asymptomatic except for episodes of prominent thrombosis and hemorrhage
372
HML Pathology:
How would you diagnose Essential thrombocythemia?
- JAK2 mutations
- abnormally large megakaryocytes and platelets
373
HML Pharmacology:
How would you treat essential throbocythemia?
Aspirin and hydroxyurea for high-risk patients (older individuals, history of thrombosis)
374
HML Pathology:
Describe tumor grading:
- graded 1-3/4
- based on differentiation; poorly differentiated tend to be highly aggressive
375
HML Pathology:
Describe tumor staging:
- determines treatment and prognosis based on spread
- TNM staging system:
Tumor: is the extent of growth.
Nodes: which and how many lymph nodes are involved
Metastasis: has the tumor metastasized
376
HML Pathology:
Which virus can develop to T-cell leukemia and lymphoma?
RNA oncogenic virus Human T-cell leukemia virus type 1
377
HML Pathology:
Which virus can develop into Burkitt lymphoma, AIDS-related lymphoma, Hodgkin Lymphoma, nasopharyngeal carcinoma?
DNA oncogenic virus Epstein-Barr virus
378
HML Pathology:
Which virus can develop into cervical carcinoma?
DNA oncogenic virus Human papillomavirus
379
HML Pathology:
Which virus can develop Kaposi sarcoma?
DNA oncogenic virus Human herpesvirus-8
380
HML Pathology:
Which virus can develop hepatocellular carcinoma?
DNA oncogenic virus Hepatitis B virus
381
HML Pathology:
Which cancer as associated with paraneoplastic syndrome: Cushing syndrome?
small cell lung cancer, pancreatic carcinoma
382
HML Pathology:
Which cancer as associated with paraneoplastic syndrome: SIADH?
small cell lung cancer, intracranial neoplasm
383
HML Pathology:
Which cancer as associated with paraneoplastic syndrome: Hypercalcemia?
squamous cell cancer of the lung, breast cancer, renal cell carcinoma
384
HML Pathology:
Which cancer as associated with paraneoplastic syndrome: Myasthenia gravis?
Thymoma
385
HML Pathology:
Which cancer as associated with paraneoplastic syndrome: Hypertrophic osteoarthropathy?
Lung cancer
386
HML Pathology:
Which cancer as associated with paraneoplastic syndrome: Migratory venous thrombosis (Trousseau syndrome)
Pancreatic carcinoma
387
HML Pathology:
Which cancer as associated with paraneoplastic syndrome: Cancer cachexia?
Generally it's a progressive loss of lean body mass and body fat, weakness, anorexia, and anemia
388
HML Pharmacology:
Name the three Nitrosoureas:
Carmustine, Lomustine, Streptozocin
389
HML Pharmacology:
What is the mechanism of Nitrosoureas?
Interfere with DNA and RNA synthesis by alkylation and protein modification. Requires bioactivation, they are lipid soluble and can cross the BBB.
390
HML Pharmacology:
Name the different categories of chemotherapy drugs:
4 points
- Tomopisomerase inhibitors
- Antimetabolites
- Microtubule inhibitors
-Cell Cycle independent drugs: Platinum agent and Alkylating agents
391
HML Pharmacology:
What are the side effects of using nitrosoureas?
5 points
- CNS toxicity (dizziness and ataxia)
- myelosuppression
- dose related nephrotoxicity
- hepatotoxicity
- pulmonary toxicity (infiltrates or fibrosis)
392
HML Pharmacology:
Name the platinum agents
Cisplatin, carboplatin, oxaliplatin
393
HML Pharmacology:
Describe the mechanism of platinum agents:
Crisslinks DNA strands inhibiting replication
394
HML Pharmacology:
Which cancers can you use platinum agents?
4 points
Testicular, bladder, ovary, and lung carcinomas
395
HML Pharmacology:
What are the side effects of using platinum agents?
5 points
- anaphylactic-like reactions*
- nephrotoxicity*
- neurotoxicity
- ototoxicity
- vomiting
396
HML Pharmacology:
How can you prevent nephrotoxicity when using platinum agents?
Amifostine (free radical scavenger) and chloride (saline) diuresis.
397
HML Pharmacology:
Describe the mechanism of Busulfan:
Alkylates DNA
398
HML Pharmacology:
When can you use Busulfan?
2 points
- leukemias/lymphomas
- also to ablate BM before transplant
399
HML Pharmacology:
What are the side effects of Busulfan?
4 points
- pulmonary fibrosis*
- hyperpigmentation
- seizures
- severe myelosuppression
400
HML Pharmacology:
Which anticancer drugs are cell cycle specific?
Antimetabolites, predominantly target the S phase
401
HML Pharmacology:
Describe the mechanism of Methotrexate:
Folic antimetabolite inhibiting dihydropfolate reductase, impairing DNA and protein synthesis
402
HML Pharmacology:
Name the uses for methotrexate:
10 points
- leukemias/lymphomas
- choriocarcinomas
- sarcomas
- abortion
- ectopic pregnancy
- Rheumatoid arthritis
- Crohn disease
- psoriasis
- IBD
- Vasculitis
403
HML Pharmacology:
Describe the side effects of methotrexate:
6 points
- Myelosuppression
- fatty change to the liver similar to ethanol and amiodarone
- skin rash
- mucositis (mouth ulcer)
- nephrotoxicity
- pulmonary fibrosis
404
HML Pharmacology:
How can you reverse the myelosuppression when taking methotrexate?
Leucovorin (folinic acid)
405
HML Pharmacology:
Describe the mechanism of action of Pemetrexed:
- pyrrolopyrimidine antifolaxe analog that requires a reduced folate carrier and activation. Inhibits Thymidylate Synthase.
406
HML Pharmacology:
When can you use Pemetrexed?
Mesothelioma and other lung cancers
407
HML Pharmacology:
Describe the side effects of Pemetrexed:
5 points
- Myelosuppression
- skin rash
- mucositosis
- diarrhea
- fatigue
*Reduce toxicities with folic acid and vitamin B12 supplementation.
408
HML Pharmacology:
Describe the MOA of 6-MP:
Blocks purine synthesis. Must be activated by Hypoxanthine guanine phosphoribosyl transferase (HGPRTase)
409
HML Pharmacology:
Describe the uses of 6-MP:
- Leukemias/lymphomas
- prevents organ rejection
- tx for RA, IBD, and SLE
410
HML Pharmacology:
Describe the side effects of 6-MP:
5 points
- myelosuppression
- hepatotoxicity
- nausea
- vomitting
*6-MP is metabolized by xanthine oxidase, so toxicity increases if inhibited (eg allopurinol)
411
HML Pharmacology:
Describe the MOA of antimetabolite Cytarabine:
Pyrimidine antagonist, terminates chain elongation. Also inhibits DNA polymerase
412
HML Pharmacology:
When can you use antimetabolite Cytarabine?
Leukemias/Lymphomas
413
HML Pharmacology:
Describe the side effects of antimetabolite Cytarabine:
- potent myelosuppression
Leukopenia, thrombocytopenia, megaloblastic anemia, neurotoxicity, and nephrotoxicity
414
HML Pharmacology:
Describe the antimetabolite 5-FU:
Pyrimidine analog that is bioactivated to 5F-dUMP. 5F-dUMP bind to flic acid inhibiting thymidylate synthase, thus inhibiting nucleic acid synthesis.
415
HML Pharmacology:
Describe the uses of antimetabolite 5-FU:
Solid tumors (eg, colon cancer, pancreatic cancers). Used topically for basal cell carcinoma of the skin.
416
HML Pharmacology:
Describe the side effects of antimetabolite 5-FU:
'Hand-foot syndrome' (dermopathy after extended use), mucositis, GI toxicity (diarrhea)
417
HML Pharmacology:
Describe the MOA of Etoposide and Teniposide:
Inhibits topoisomerase II (increases DNA damage)
418
HML Pharmacology:
Describe the uses of Etoposide and Teniposide:
Solid tumors (particularly testicular and small cell lung cancer), leukemias, and lymphomas
419
HML Pharmacology:
Describe the side effects of Etoposide and Teniposide:
- Myelosuppression
- GI upset
- alopecia
420
HML Pharmacology:
Describe the MOA of Irinotecan and Topotecan:
Inhibit topoisomerase I (prevents DNA unwinding and replication)
421
HML Pharmacology:
Describe the use of Irinotecan and Topotecan:
2 points
- Colon cancer (irinotecan)
- Ovarian and small cell lung cancers (topotecan)
422
HML Pharmacology:
Describe the side effects of Irinotecan and Topotecan:
2 points
- Severe myelosuppression
- diarrhea
423
HML Pharmacology:
Describe the MOA of Vinca Alkaloids (Vincristine, Vinblastine):
Prevents microtubule formation by interfering with tubule binding. Mitotic spindle does not form, M phase does not proceed.
424
HML Pharmacology:
Describe the uses of Vinca Alkaloids (Vincristine, Vinblastine):
Leukemias/lymphomas and solid tumors
425
HML Pharmacology:
Describe the side effects of Vinca Alkaloids (Vincristine, Vinblastine):
- 2 points
- ViNcristine causes Neurotoxicity
- VinBlastine causes bone marrow toxicity
426
HML Pharmacology:
Describe the MOA of Taxanes (Paclitaxel and Docetaxel):
Prevent microtubule breakdown by stabilizing tubilin already bound in mitotic spindles. M phase does not complete.
427
HML Pharmacology:
Describe the uses of Taxanes (Paclitaxel and Docetaxel):
Solid tumors (eg, ovarian and breast carcinomas)
428
HML Pharmacology:
Describe the side effects of Taxanes (Paclitaxel and Docetaxel):
3 points
- Myelosuppression
- alopecia
- hypersensitivity
429
HML Pharmacology:
Describe the MOA of Ixabepilone and Epothilone:
Microtubule inhibitors active in the M phase of the cell cycle.
430
HML Pharmacology:
Describe the uses of Ixabepilone and Epothilone:
Breast cancers
431
HML Pharmacology:
Describe the side effects of Ixabepilone and Epothilone:
3 points
- Myelosuppression
- hypersensitivity reactions
- neurotoxicity (peripheral sensory neuropathy)
432
HML Pharmacology:
Describe the MOA of Cetuximab and Panitumumab:
- Cetuximab is an antibody directed against the extracellular domain of the EGFR, decreasing cellular growth, proliferation, invasion, metastasis, and angiogenesis
- Panitumumab is a human monoclonal antibody directed against the EGFR and blocks signaling
433
HML Pharmacology:
Describe the uses for Cetuximab and Panitumumab:
Colorectal cancer and some head and neck cancers
434
HML Pharmacology:
Describe the side effects of Cetuximab and Panitumumab:
- Cetuximab can cause acneiform skin rash, hypersensitivity infusion reaction, and hypomagnesemia
- Infusion related reactions less likely with Panitumumab
435
HML Pharmacology:
Name the Anti-BCR-ABL agents:
Imatinib, Dasatinib, and Nilotinib
436
HML Pharmacology:
Describe the MOA of anti-BCR-ABL agents:
- Imatinib inhibits BCR-ABL tyrosine kinase specific to CML by blocking the binding site of ADP substrate
- Nilotinib is a more potent BCR-ABL inhibitor
- Dasatinib inhibits both BCR-ABL and Src kinases
437
HML Pharmacology:
Describe the uses of anti-BCR-ABL agents:
CML with the t(9;22) Ph chromosomal translocation and GI stroll tumors (GISTs)
438
HML Pharmacology:
Describe the side effects of anti-BCR-ABL agents:
Mild. Potential interactions exist with other drugs, grapefruit, and St. John's wort, which are also metabolized by the CYP3A4 system
439
HML Pharmacology:
Describe the uses of Rituximab:
4 points
- Non-hodgkin Lymphoma
- CLL
- inflammatory bowel disease
- RA
440
HML Pharmacology:
Describe the side effects of Rituximab:
5 points
- Infusion reactions
- tumor lysis syndrome
- skin and mouth reactions
- infections
- increased risk of progressive multifocal leukoencephalopathy
441
HML Pharmacology:
Describe the MOA of anti proteasome, Bortezomib:
Interferes with proteasome, which normally control the degradation of proteins regulating cell proliferation. Causes apoptosis in tumor cells.
442
HML Pharmacology:
Describe the uses of anti proteasome, Bortezomib:
Multiple myeloma, mantle cell lymphoma
443
HML Pharmacology:
Describe the side effects of anti proteasome, Bortezomib:
4 points
- GI effects
- asthenia
- peripheral neuropathy
- myelosuppression
444
Uworld HML Pathophysiology:
What would you see in peripheral blood smear in hemolytic anemia?
- Reticulocytosis
- Spherocytes
- Nucleated RBCs
445
Bootcamp: PNH Pharmacology/ Microbiology
When treating a pt with PNH, what media does the organism more susceptible as result of the medication grow on?
Thayer-Martin agar
- a culture medium containing vancomycin, trimethoprim, colistin, and nystatin
- Neisseria spp. would grow
446
Pathophysiology: Abnormal Oxygen Levels
Describe Methemoglobinemia:
- Life threatening condition where the Ferrous (Fe2+)/ heme iron is oxidized to the ferric (Fe3+) state
- congenital or acquired
- agents that can cause include primaquine, dapsone, nitrites, and local anesthetics.
- results in conformational changes causing increased oxygen affinity, reducing oxygen delivery to peripheral tissues, reduces the partial pressure of oxygen (P50) seen as a leftward shift of the Oxygen-Hb dissociation curve
- signs and symptoms include AMS, cyanosis, and dark brown "chocolate" appearance of the blood after exposure to an oxidizing agent
- Tx: reducing agents like methylene blue or ascorbic acid (Vitamin C) to convert ferric iron back to ferrous state
