Serum Iron: Iron
TIBC: How much transferrin is in the blood (bound or not)
% Saturation: Iron bound to Transferrin
Serum Ferritin: Stored iron
Card 2
Hookworms can cause what? What are the 3 we should know?
Answer
Iron deficiency anemia
Necator americanus
Ancylostoma duodenale
Strongyloides stercoralis
Card 3
With a gastrectomy, what happens to iron absorption? Why?
Answer
Acid maintains Fe²⁺ state (absorbed form).
Gastrectomy leads to decreased acid production and less Fe²⁺ for absorption
Nomenclature Note:
Ferrous = Fe²⁺
Ferric = Fe³⁺
Card 4
The initial phase of Iron Deficiency Anemia presents as _______.
Answer
Normocytic.
Card 5
Free Erthyrocyte Protoporphyrin (FEP) in IDA and ACD?
Answer
This will be increased in iron deficiency anemia (IDA) and anemia of chronic disease (ACD).
Because iron levels are reduced, more of the protoporphyrin will be free.
Card 6
Dysphagia, IDA, and esophageal webs are the triad characteristic of which syndrome?
Answer
Plummer-Vinson Syndrome (Plumbers DIE)
Card 7
Anemia of Chronic Disease initially presents as a __________ anemia.
Answer
Normocytic
Card 8
What are these cells called? What material is staining blue, and why has it accumulated?
Answer
These are called sideroblasts. The material staining blue are iron-laden macrophages. Iron accumulates due to lack of adequate protoporphyrin production. One can imagine that lead poisoning, which inhibits porphyrin synthesis, would cause a sideroblastic anemia
Card 9
Most common form of congenital sideroblastic anemia is due to?
Answer
Defect in aminolevulinic acid synthetase (ALAS) (often X-linked)
Card 10
Lead can denature which two enzymes?
Answer
ALA-Dehydrogenase (ALAD), which converts dALA to porphobilinogen
Ferrochelatase, which catalyzes the addition of heme to the final porphyrin ring
Card 11
Lab Findings in Sideroblastic Anemia (4)?
Answer
"Iron Overloaded State"
Increased iron (↓ protoporphyrin ⇒ ↑ Fe)
Increased % saturation (↑ Fe ⇒ ↑ Fe-bound transferrin)
Increased ferritin (upregulated since more iron needs to be stored)
Decreased TIBC (transferrin downregulated because less iron needs to be carried in blood)
Shares the same lab findings with hemochromatosis.
Card 12
How would you characterize the differences in globin chain synthesis that cause thalassemias and sickle cell anemia?
Alpha Thalassemia and Beta Thalassemia are distinguished in one way by the types of mutations which cause them. Describe:
Answer
Alpha Thalassemia: due to gene deletions
Beta Thalassemia: due to gene mutations (often resulting in splice variants)
*Note that beta thalassemia mutations are often associated with regions of DNA that act as promotors or enhancers, or which promote alternative splicing
Card 14
What is HbH? What condition might it be seen in?
Answer
HbH = β-hemoglobin tetramers that can damage RBCs
HbH can be seen on electrophoresis in cases of severe α-thalassemia (3 allele deletion)
Card 15
What will you see on electrophoresis in someone who has alpha thalassemia 4 deletion?
Answer
"Someone" is a generous term here. A full 4 allele deletion almost ubiquitously results in hydrops fetalis. Nonetheless, if you do electrophoresis, you will see "Hb Barts" - a tetramer of gamma chains. Sometimes called "Barts disease"
Card 16
What results would one expect on β-thalassemia minor hemoglobin electrophoresis?
Answer
Beta Thalassemia Minor Hb Electrophoresis:
Slightly decreased HbA to ~93% (N = 97%)
Increased HbA₂ to 5% (N = 2.5%)
Increased HbF to 2% (N = 1%)
Beta Thalassemia Major Hb Electrophoresis:
HbA2 and HbF with little or no HbA
Card 17
Describe the pathophysiology, characteristic imaging, and clinical findings of β-Thalassemia Major
Answer
Alpha tetramers aggregate and damage RBCs (similar to Heinz)
Ineffective erythropoesis leads to massive erythroid hyperplasia, causing:
1.) Extramedullary hematopoesis in
liver and spleen (hepatosplenomegaly),
skull (crewcut appearance) and
facial bones (chipmunk-like facies)
2.) Extravascular hemolysis (mainly in spleen)
3.) Risk of aplastic crisis upon parvovirus B19 infection
Card 18
What is the difference between Megaloblastic Anemia and Macrocytic Anemia?
Answer
Megaloblastic Anemia: due to folate/B12 deficiency; hypersegmented neutrophils + megaloblastic change in rapidly dividing cells
Macrocytic Anemia: due to alcoholism, liver disease, or drugs (5-FU);
(no hypersegmented neutrophils or megaloblastic changes in rapidly dividing cells)
Card 19
Causes of Vitamin B12 deficiency (4)?
Answer
Pancreatic insufficiency: pancreas produces enzymes to cleave B12 from R-binder (protein that is secreted by the salivary gland and binds to B12 to protect it from degradation in the acidic stomach; hands B12 off to IF in duodenum).
Autoimmune destruction of parietal cells (decreased secretion of IF)
Damage to terminal Ileum: Crohn's Disease or Diphyllobothrium latum (tapeworm).
Dietary deficiency: rare, except in vegans
Card 20
How does B12 deficiency cause neurotoxicity? What 3 tracts are affected?
Answer
B12 defieincy will cause a build up of methylmalonic acid in the spinal cord, specifically, in the myelin. This results in degeneration of the posterior columns (vibratory sensation), the lateral corticospinal tract (spastic paralysis), and spinocerebellar tracts (proprioception).
This is referred to as subacute combined degeneration.
Card 21
What does the reticulocyte count tell you about a normocytic anemia?
Answer
Helps you differentiate between anemia caused by peripheral destruction or underproduction of RBCs
Card 22
How do you identify reticulocytes on bone marrow biopsy or blood smear?
Answer
Identified as large cell with bluish cytoplasm. Presence of RNA in the cytoplasm causes the bluish tone
Card 23
Why is the reticulocyte count falsely elevated in an anemic patient? How do we adjust it?
Answer
RC is falsely elevated because it is measured as a percentage of total RBCs. A decrease in total RBCs therefore elevates percentage of reticulocytes without changing their absolute quantity.
CRC = RC * (HCT/45)
where
RC = # reticulocytes / (# RBCs + # reticulocytes)
RC: reticulocyte count
CRC: corrected " "
Card 24
In a normocytic anemia, how can you tell if it is a result of underproduction or destruction?
What happens to haptoglobin levels in the early stages of an intravascular hemolytic anemia?
Answer
Hb will spill into blood and immediately bind haptoglobin (a scavenger molecule). (Hb-Hapto Complex). Haptoglobin takes Hb to the spleen to get re-processed.
Thus, an early change in intravascular hemolysis normocytic anemia is a decrease in serum haptoglobin levels.
Card 27
What is an early change in intravascular hemolysis?
Answer
Decrease in serum haptoglobin levels because haptoglobin binds to resulting hemoglobin spill into the blood.
Card 28
Blood and urine findings in normocytic anemia due to intravascular hemolysis (3):
Answer
Hemoglobinemia.
Hemoglobinuria
Hemosiderinuria: iron will be taken up by kidney epithelial cells and deposit as hemosiderin. Days after, cells will slough off and into the urine.
Card 29
What disease demonstrates an increased mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)?
Answer
Hereditary spherocytosis. Note that if MCHC is elevated, we are almost definitely dealing with spherocytosis
Card 30
What cells does Parvovirus B19 infect?
Answer
Erythroid precursors
Card 31
How is hereditary spherocytosis diagnosed?
Answer
Osmotic Fragility Test
Increased fragility in hypotonic solution
Spherocyte will burst
Tx: splenectomy
Card 32
What is this?
Answer
Howell-Jolly body (a fragment of nuclear material remaining in the RBC, since splenic macrophages no longer phagocytose it). Characteristic of asplenics (HS, SS, etc.)
Card 33
Why are sickled cells sickled?
Answer
HbS polymerizes (not a covalent bond) when deoxygenated. Thus, polymers aggregate into needle-like structures called sickle cells.
Card 34
What is the common vaso-occlusive manifestation of sickle-cell disease that one classically sees in infants?
Answer
Dactylitis: swollen hands and feet due to vaso-occlusive infarcts in the bones
Card 35
Howell Jolly Bodies are seen in which diseases?
Answer
Hereditary spherocytosis (especially post-splenectomy) and sickle cell disease
Card 36
What is Acute Chest Syndrome?
Answer
Vasoocclusive crisis in pulmonary microcirculation in patients with sickle cell disease (SCD).
Sx: chest pain, dyspnea, pulmonary infiltrates
Precipiated by pneumonia
Most common cause of death in adults with SCD.
Card 37
What is the most common cause of death of adults with sickle cell disease?
Answer
Acute Chest Syndrome: vaso-occlusion in the pulmonary microcirculation
Card 38
Vasoocclusive crises in the kidneys leads to what pathology?
Answer
Renal papillary necrosis. Results in hematuria and proteinuria.
Card 39
Why do people with sickle cell trait have few symptoms? What causes the symptoms they have?
Answer
Less than 50% HbS in blood does not induce sickling. (HbS Hb electronphoresis = ~55% HbA, 43% HbS, 2% HbF)
Note that in the renal medulla, extreme hypoxia and hypertonicity causes sickling even in those with SS trait. This results in microinfarctions. Leads to hematuria and inability to concentrate the urine.
Card 40
What is a metabisulfite screen?
Answer
Metabisulfite is a chemical that induces cell sickling provided any amount of HbS exists; test is positive in both sickle cell disease and trait.
Card 41
Difference between Hb Electrophoresis in HbS and HbSS?
Autosomal recessive mutation in β chain of hemoglobin.
Glu → Lys (negative AA is changed to a positive AA)
HbC crystals can be seen on blood smear.
Card 43
What disease is this histological finding associated with? What is the pathogenesis?
Answer
Hemoglobin C crystal on blood smear.
Glutamic Acid → Lysine of β chain.
Card 44
Paroxysmal Nocturnal Hemaglobinuria - describe the pathogenesis:
Answer
Acquired defect in myeloid stem cell. RBCs lose expression of GPI via spontaneous de-expression in the myeloid progenitor. DAF and MIRL can no longer be anchored to the RBC, and so cells are susceptible to complement destruction.
Sleep induces a mild respiratory acidosis. This activates complement.
Card 45
Two blood findings and two urine findings in paroxysmal nocturnal hemoglobinuria?
Answer
During hemolysis:
decreased serum haptoglobin - binds Hb to scavenge iron
hemoglobinemia - haptoglobin only saves small amt of Hb; excess Hb builds up
hemoglobinuria - Hb leaks into urine (b/c water-soluble)
Days after hemolysis:
hemosiderinuria - renal tubular cells pick up and convert Hb to Fe, which accumulates as hemosiderin; excreted when cells are shed
*You would see these patterns in all types of intravascular hemolysis
Card 46
How do you screen for paroxysmal nocturnal hemoglobinuria?
Answer
Sucrose test (activates complement, e.g. MBL pathway) used for screening.
Confirmatory test is acidified serum test (acid activates complement, like nocturnal acidosis) or
flow cytometry to detect lack of CD55 (DAF) or CD59 (MIRL) on RBC surface
Memory Associations:
∆CD55: LL, e.g. "no lol, idgaf"
∆CD59: HB, e.g. "no hobbies, me IRL"
Card 47
Main cause of death in patients with paroxysmal nocturnal hemoglobinuria
Answer
Thrombosis of hepatic, portal, and cerebral veins.
Destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis.
Card 48
2 complications that can develop over time from paroxysmal nocturnal hemoglobinuria?
Answer
Iron deficiency anemia (due to chronic loss of hemoglobin in the urine)
Acute Myeloid Leukemia
*Important also to note that PNH increases risk of thrombosis, as exposed contents of lysed cells (esp. phospholipids) can induce clotting cascade
How can we screen for and then confirm a diagnosis of G6PD deficiency?
Answer
Screening: Heinz preparation used to visualize Heinz bodies (body of precipitated Hb)
Confirmation: Enzyme studies performed several weeks after an episode confirm the deficiency
Card 51
Besides hereditary spherocytosis, what other disease is associated with spherocytes?
Answer
IgG mediated Hemolytic Anemia (warm agglutitin)
Note that this is an extravascular hemolysis - IgG deposition on RBC surface causes removal of RBCs by the spleen. This is in contrast to the IgM-mediated cold aggultinin hemolytic anemia, which fixes complement and induces intravascular hemolysis.
Card 52
IgG autoimmune hemolytic anemia is associated with what disorders? What causes it, and what is the treatment?
Answer
SLE (most common) and CLL
Drugs:
Classically, penicillin (Ab targets drug-RBC complex) and cephalosporins.
More recently, methyldopa (induce production of anti-self-Ag auto-Abs)
Treatment:
Steroids - slow down Ab production
IVIG - splenic Mφ cons IVIG instead of RBC-bound Ig
splenectomy - source of both Ab and hemolysis
Card 53
IgM Mediated Autoimmune Hemolytic Anemia - pathogenesis and inducing conditions?
Answer
Binds RBCs and fixes complement in COLD temperatures of extremities (cold agglutinin). Associated with mycoplasma pneumoniae + infectious mononucleosis (EBV).
Note that this is a primarily intravascular hemolysis - IgM fixes complement
Card 54
Direct Coombs test vs. Indirect: describe what each detects
Answer
Direct Test: the presence of antibody or complement on RBCs
Indirect Test: the presence of antibody in the patient's serum
Card 55
What is a myelophthisic process?
Answer
A pathologic process that replaces bone marrow.
impaired hematopoesis → pancytopenia
Card 56
Is malarial anemia a result of extravascular or intravascular hemolysis?
Answer
Trick question, it's actually both.
There is direct intravascular rupture by parasites, and
extravascular hemolysis via splenic uptake
Card 57
What are the clinical and histologic features of mycosis fungoides?
Answer
Mycosis fungoides is the most common form of cutaneous T-cell lymphoma.
Clinical features include: skin rash, plaques, and nodules; Aggregates of the CD4 cells in the epidermis are called Pautrier microabscesses.
These cells can spread to the blood and cause Sezary syndrome (Sezary cells with cerebriform nuclei seen on peripheral blood smear).
Card 58
Histology of nodular sclerosing lymphoma (a subtype of hodgkin lymphoma)?
Answer
Lymph node follicles are divided by bands of sclerosis. Reed-Sternberg cells are present in lake-like spaces (lacunae)
*Somewhat important to note nodular sclerosing lymphoma can have eosinophils, lymphocytes, basophils, etc, but don't get tricked into thinking it's "mixed cellularity". If it has fibrosis, it's nodular sclerosing subtype.
Card 59
Acute Myeloid Leukemia classically stains positively for which marker?
Answer
MPO. Alternatively, Auer rods may be visible on blood smear within the immature myeloid cell.
*Note that acute monocytic and acute megakaryoblastic subtypes of AML are commonly MPO negative
*Note also that this is in contrast to TdT-positivity seen in ALL.
Card 60
Which AML subtype is common in patients with Down syndrome who are under the age of 5?
Answer
Acute megakaryoblastic leukemia
vs. ALL, assoc w/ Down syndrome after age 5
Card 61
Which AML subtype classically presents with gum infiltration? Does this subtype stain positive for MPO?
Answer
Acute monocytic leukemia (a subtype of AML); usually it is MPO negative
Card 62
The t(15;17) translocation is characteristic to which leukemia subtype? What is the treatment?
Answer
Characteristic of acute promyelocytic leukemia (a subtype of AML).
The t(15;17) translocation involves the Retinoic Acid Receptor.
Treatment w/ ATRA (all trans-retinoic acid) - binds to RAR and induces maturation of promyelocytes into neutrophils
Card 63
What classic marker distinguishes Acute Lymphoblastic Leukemia from Acute Myelogenous Leukemia?
Answer
TdT, i.e. DNA polyermase, which is present ONLY in the nucleus of premature T and B cells (i.e. cells of a lymphoid lineage), and is thus specific to ALL
By contrast, AML classically stains positive for MPO; however, notable subtypes, such as monocytic and megakaryoblastic leukemia, both tend to lack MPO.
Card 64
Which ALL subtype is more common, B or T cell? What cell surface markers distinguish the two?
Answer
B-ALL is more common - CD10+, CD19+, CD20+ are characteristic markers
T-ALL - CD3+, CD4+, CD7+ (CD2-CD8 all possible). T-ALL is notably absent of CD10
Card 65
In B-ALL, which common translocation is associated with a good prognosis? Which rarer translocation has a poor one?
Answer
t(12;21) is a classic and common translocation seen in B-ALL (particularly in children). Has a great prognosis.
t(9;22) is known as the Philadelphia chromosome. The Philadelphia chromosome is most characteristic of CML. However, it can be seen seen in adult ALL as well (though this is rare; e.g. CML -> ALL blast crisis) - we call this Ph+ ALL. Prognosis is poor.
Card 66
When does T-ALL present? How does it present?
Answer
It presents in teenagers as a mediastinal (thymic) mass; called acute lymphoblatic lymphoma because of this mass
Card 67
What is the characteristic pattern of cell-surface markers for Chronic Lymphocytic Leukemia (CLL)?
Answer
CD5 and CD20 co-expression; You can remember CD20 because it is a B-cell marker, and CLL is a proliferation of naïve B-cells
Card 68
In what type of leukemia and lymphoma would you see a "smudge" cell?
Answer
CLL and SLL (small lymphocytic lymphoma, which is the proliferation of CLL into lymph nodes). Smudge cells are fragile neoplastic B lymphocytes that break when prepared on a slide
Card 69
What is the most common cause of death in patients with CLL?
Answer
Infection due to hypogammaglobulinemia
Card 70
What type of cell undergoes neoplastic proliferation to cause hairy cell leukemia?
Answer
HCL is a proliferation of mature B cells
Card 71
What hematologic malignancy is characterisitically positive for tartrate-resistant acid phosphatase (TRAP)?
Answer
Hairy Cell Leukemia
Card 72
What are 2 common clinical features of hairy cell leukemia? What common feature of leukemia/lymphoma is not seen in HCL?
Answer
Splenomegaly, dry tap on bone marrow aspiration (marrow fibrosis).
Lymphadenopathy is usually absent in HCM.
Card 73
Where in the spleen do hairy cells accumulate in hairy cell leukemia?
Answer
Red pulp
Card 74
What drug is the mainstay of treatment for Hairy Cell Leukemia? What is its mechanism?
Answer
2-CDA (cladribine)
It is adenosine deaminase (ADA) inhibitor: 2-CDA resists degradation by ADA, so
1.) adenosine accumulates to toxic levels in neoplastic B cells
2.) incorporation int DNA induces ds breaks
*Tie-in: remember that ADA deficiency is a common cause of SCID
Card 75
What virus can lead to Adult T-Cell leukemia/lymphoma (ATLL)? What parts of the world is this virus seen in?
Answer
HTLV-1; most commonly seen in Japan and the Carribean
Card 76
What hematologic malignancy typically presents with rash, generalized lymphadenopathy, and lytic (punched-out) bone lesions with hypercalcemia?
Answer
Adult T-cell leukemia/lymphoma (ATLL)
Card 77
What malignancy clinically presents with lytic (punched-out) bone lesions (with hypercalcemia) in the absence of a rash?
Answer
Multiple Myeloma
Contrast this with adult T cell leukemia/lymphoma (ATLL), which presents with lytic bone lesions in addition to rash, hepatosplenomegaly (HSM), and lymphadenopathy (LAD)
Card 78
Which two leukemias tend to present with a rash (representing cutaneous infiltration)?
Answer
Mycosis fungoides and Adult T cell Leukemia (ATLL)
*Note that both of these are cutaneous T cell lymphoma/leukemias
Card 79
What is a pautrier microabscess? What malignancy is is characteristic of?
Answer
Aggregrates of neoplastic cells in the epidermis - not a true microabscess, since there are no neutrophils.
Seen in Mycoses fungoides
Card 80
How does Sezary syndrome occur? What does the characteristic cell look like?
Answer
Occurs in mycosis fungoides when Sezary cells spread to the blood;
Sezary cells are described as having a "cerebriform nucleus" (looks like a brain)
Card 81
What is significant about a t(9;22) translocation?
Answer
This specific translocation generates what is termed a "Philadelphia chromosome". The product of this translocation is the BCR-ABL fusion protein, a constiutively active tyrosine kinase that is specifcally targetable with the small molecule imatinib.
*Note that the t(9;22) translocation is classically associated with CML, but is also sometimes seen in cases of adult ALL.
Card 82
Which hematologic malignancies can carry the t(9;22) translocation?
Answer
CML; (Ph+) B-ALL
Card 83
A patient diagnosed with CML has splenomegaly, suggesting progression to accelerated form of the disease. What complications may shortly occur?
Answer
The malignancy may:
transform into AML (2/3 of cases)
or ALL (1/3 of cases)
This can be termed "blast crisis"
Card 84
How do you distinguish CML from a leukemoid reaction?
Answer
1) Negative Leukocyte Alkaline Phosphatase (LAP) stain
2) increased basophils (basophilia is a characteristic sign of CML)
3) t(9;22) positive
Card 85
What 3 myeloproliferative disorders are associated with JAK2 Kinase mutations?
What is the most common venous thrombosis that can arise in patients w/ polycythemia vera?
Answer
Hepatic vein thrombosis leading to Budd Chiari syndrome
Card 87
What is the treatment for CML?
Answer
Imatinib (Gleevec), a small molecule that is directed specifically at the BCR-ABL fusion tyrosine kinase.
*Note: imatinib is also one of three approved treatments for gastrointestinal stromal tumors (GIST). The other two medications are sunitinib and regorafenib
Card 88
Why do polycythemia vera patients get itchy after bathing?
Answer
An important concept to understand with all myeloproliferative disorders is that all cells of the myeloid lineage are increased to some degree - the disorder is named for the cell that is most increased. In PV, mast cells are overproduced. These release histamine upon contact with hot water, causing the characteristic itching.
Card 89
How do you distinguish polycythemia vera from reactive polycythemia?
Answer
One needs to understand the differences in EPO levels and SaO₂ in PV vs. reactive polycythemia due to altitude, and due to cancer. A table helps:
EPO SaO₂
PV down normal
Alt up down
Tum up normal
This makes sense: in PV, a myeloid defect, not EPO, is not driving RBC proliferation, so EPO is down. Oxygen saturation has not changed. In altitude RP, EPO is driven up because of lower oxygenation. In tumor RP, the tumor is making the EPO.
Card 90
What tumor characteristically produces EPO, leading to a reactive polycythemia?
Answer
Renal cell carcinoma
Card 91
What are the 3 key clinical features of myelofibrosis?
Answer
1) Splenomegaly due to extramedullary hematopoiesis
2) leukoerythroblastic smear (tear drop cells, nucleated RBCs, and immature granulocytes all caused by marrow crowding/fibrosis, seen on blood smear)
3) and increased risk of infection/thrombosis/bleeding (due to increased megakaroyblastic proliferation/fibrosis/pancytopenia)
Card 92
In a case of infectious mononucleosis, which part of the lymph node and which part of the spleen become hyperplastic?
Answer
EBV is a viral infection, so we expect the regions where T cells are housed to expand.
In the LN, this is the paracortex
In the spleen, these are the perarterial lymphoid sheaths (PALS)
Card 93
When would you see follicular hyperplasia of the lymph node?
Answer
Follicular hyperplasia (B-cell region) is seen in cases of rheumatoid arthritis and in early stages of HIV infection
Card 94
What malignancy is associated with a t(14;18) translocation?
Answer
Follicular lymphoma
This translocation places the Bcl-2 gene onto the Ig heavy chain gene locus
*Often described as having "notched" nuclei
Card 95
How does the translocation t(14;18) meaningfully alter protein expression?
Answer
The BCL2 gene encodes for the anti-apoptotic signaling protein Bcl-2, and is found on chromosome 18. By translocating to the Ig heavy chain locus on chromosome 14, Bcl-2 becomes overexpressed, suppressing apoptosis of malignant cells, driving the development of follicular lymphoma
Card 96
What is the mainstay of treatment for follicular lymphoma?
Answer
Low-dose chemotherapy or rituximab (anti-CD20 mAb)
*However, it's a very important concept to understand that follicular lymphoma has a very indolent course - treatment to not always commence upon initial discovery, especially if the chemo has negative effects on QOL. Often it is simply observed. This delay in treatment has not been associated with any loss in mortality.
Card 97
How do you distinguish follicular lymphoma from reactive follicular hyperplasia?
Answer
1.) Disruption of normal LN architecture
2.) Lack of tingible body (paler) macrophages in germinal centers
3.) Bcl-2 expression in follicles
4.) Monoclonality, (follicular hyperplasia is polyclonal)
Card 98
What malignancy proliferates in the mantle zone of a lymph node? Where is the mantle zone of a lymph node?
Answer
Mantle cell lymphoma
The mantle zone is adjacent to the germinal center
Card 99
The t(11:14) translocation is characteristic of which hemotologic malignancy? How does this translocation drive the malignancy?
Answer
Characteristic of mantle cell lymphoma;
Cyclin D1 on chromosome 11 is translocated to the Ig heavy chain locus on Ch 14. Overexpression of Cyclin D1 promotes G1 to S transition in the cell cycle, causing uninhibited neoplastic proliferation
Card 100
What type of lymphoma is classically associated with chronic inflammatory states like: Hashimoto thyroiditis, Sjögren syndrome, and H. pylori gastritis?
Answer
Marginal zone lymphoma
*Note that a marginal zone lymphoma, if occurring in mucosal sites, is reffered to as a "MALToma". Gastric MALTomas typically recede following treatment of underlying H. pylori infection
Card 101
Where in the body does the African form of Burkitt lymphoma arise? What about the sporadic form?
Answer
African form usually arises in the jaw;
Sporadic in the abdomen
Card 102
The t(8;14) translocation is characteristic of which hematologic malignancy? How does this translocation alter protein expression?
Answer
This is a common (though not ubiquitous) translocation driving Burkitt Lymphoma.
The gene for c-myc on chromosome 8 is translocated to the Ig heavy chain locus on chromosome 14 (as they all are). This causes overexpression of the c-myc oncogene.
Note: nasopharyngeal carcinoma shares EBV etiology, but lacks t(8;14) pathogenesis
Card 103
What malignancy demonstrates a classic "starry-sky appearance" on histology?
Answer
Burkitt lymphoma
Card 104
What is the most common form of Non-Hodgkin lymphoma?
Answer
Diffuse large B-cell lymphoma
*Very important to note that DLBCL is characteristically CD20+. It grows in "sheets". Can arise from transformation of a low-grade lymphoma, classically follicular lymphoma
Card 105
What cell is know for its "owl-eye nuclei"? What disease is it pathognomonic for? What cell surface receptors does it express?
Answer
Reed-Sternberg cell seen in Hodgkin lymphoma
Expresses: CD15, CD30
Card 106
What is a lacunar cell?
Answer
A lacunar cell is a Reed-Sternberg cell that can be observed in the lake-like spaces between fibrotic bands - seen in the nodular sclerosing form of hodgkin lymphoma.
Several "lacunar cells" are present. They are characterized by multilobated nuclei, small nucleoli, and abundant, pale cytoplasm that often "retracts" during tissue fixation and sectioning, leaving the nucleus in what appears to be an empty space (lacune). "Mummified cells" are neoplastic cells that contain condensed cytoplasm and pyknotic reddish nuclei. A "mummified" Reed-Sternberg cell is in the upper left corner.
Card 107
Which subtype of hodgkin lymphoma has the best prognosis?
Answer
Lymphocyte-rich has the best prognosis of all subtypes.
*Lymphocyte-depleted hodgkin lymphoma, by contrast, has the worst prognosis. It is typically only seen in the elderly and HIV-positive patients
*Mixed-cellularity is associated with abundant eosinophils (IL-5 secreted by RS cells)
Card 108
How do the neoplastic cells in multiple myeloma induce the formation of lytic bone lesions?
Answer
Neoplastic plasma cells activate the RANK receptor on osteoclasts, which upregulates their activity, causing lytic bone lesions - typically in the vertebrae and skull.
Card 109
What type of protein is excreted in the urine in patients with multiple myeloma?
Answer
Free immunoglobulin light chain protein, known as Bence-Jones protein
Remember that multiple myeloma, being a malignant proliferation of plasma cells, is obviously associated with increased production of monoclonal IgG or IgA (seen as an M-spike on serum electrophoresis). This results in an increased circulation of free immunoglobulin light chains (which also causes an AL amyloidosis)
Card 110
What immunoglobulins can cause an M-spike on serum protein electrophoresis (SPEP) in multiple myeloma?
Answer
Most commonly IgG or IgA
Card 111
What are the 3 fates of the free light chain that is produced in multiple myeloma?
Answer
1. Deposition into the blood vessels and tissue leading to primary AL amyloidosis
2. Proteinuria (excretion of Bence-Jones protein)
3. Deposition into the kidney tubules, leading to renal failure (myeloma kidney)
Card 112
What is MGUS?
Answer
Monoclonal gammopathy of undetermined significance: defined as an observed M spike on SPEP, w/o the clinical features of multiple myeloma.
*1% of all patients with MGUS develop multiple myeloma each year
Card 113
In which type of disease do you see Birbeck (tennis racket) granules on electron microscopy? What are the surface markers are associated with them?
Answer
Seen in Langerhans cell histiocytosis
Langerhans cells are CD1a+ and S100+
Card 114
An IgM-derived M-spike on serum protein electrophoresis is indicative of what hematologic malignancy?
Answer
Waldeström macroglobulinemia
vs. hyper-IgM syndrome (benign)
Card 115
The visual and neurologic deficits seen in Waldenström macroglobulinemia have what etiology?
Answer
Risk of retinal hemorrhage and stroke are increase due to increased serum viscosity, which is in turn caused by the increase in circulating IgM
Card 116
How is Waldenström Macroglobulinemia treated?
Answer
With plasmapheresis, to remove excess IgM
Card 117
What three diseases comprise langerhans cell histiocytosis?
What cell surface marker is classically present in DLBCL? From what malignancy does DLBCL typically arise?
Answer
CD20; follicular lymphoma
*HIGH YIELD: CLL is also quite capable of transforming into DLBCL - between 5-10% of cases do so - and this is called a richter transformation. This transformation carries an extremely poor prognosis.
Card 119
Which part of the blood vessel is affected in atherosclerosis?
Answer
The intima of arteries in either medium or large blood vessels.
Card 120
What type of arteriolosclerosis does malignant HTN result in? What does it look like?
Answer
Hyperplastic arteriolosclerosis (thickening of the blood vessel wall due to hyperplasia of smooth muscle) that looks like "onion-skin" appearance.
Card 121
If the kidney has a "flea bitten" appearance to it, what does that indicate?
Answer
Renal failure due to hyperplastic arteriolosclerosis (from malignant HTN)
Card 122
What is the major complication of a thoracic aortic aneurysm?
Answer
Dilatation of the aortic valve root resulting in aortic valve insufficiency
aneurism- vessel intact;
vs. dissection- leak causes tamponade
Card 123
Where does an abdominal aortic aneursym occur? (give landmarks above and below)
Answer
Below the renal arteries (L1-2) and above the aortic bifurcation (L4)
Card 124
What is depicted in this histological specimen?
Answer
Atherosclerotic embolus - note the cholesterol crystals apparent in the core
Card 125
What is depicted in this histological specimen?
Answer
Hyaline arteriolosclerosis
vs. hyperplastic arteriolosclerosis:
Card 126
What is depicted in the histological specimen below?
Answer
Hyperplastic arteriolosclerosis
vs. hyaline arteriolosclerosis:
Card 127
The vasculitides are divided into what 3 categories? What vessels are involved in each?
Answer
1) Large-vessel: involves the aorta and major branches
2) Medium-vessel: involves the muscular arteries that supply organs
3) Small-vessel: involves arterioles, capillaries, venules
What will biopsy reveal in a case of temporal arteritis? How does biopsy factor in to diagnosis?
Answer
Biopsy shows inflamed vessel walls
with giant cells
and intimal fibrosis.
Because lesions are segmental,
biopsy must include long segment of vessel,
and negative biopsy does not exclude diagnosis.
*Note: can biopsy termporal artery b/c of many collaterals
Card 133
What is the treatment for giant cell arteritis?
Answer
Corticosteroids, surgery (e.g. stent, bypass)
Card 134
What is takayasu arteritis (what's typically involved)?
Answer
A granulomatous arteritis that involves the aortic arch at branch parts (think of it as temporal arteritis that occurs in more centrally-located vasculature).
Card 135
In whom does takayasu arteritis present? How does it present?
Answer
1) Classically, young asian females (< 50).
2) Clinically presents as:
- Weak/absent UE pulse (aortic a. branches)
- Neuro symptoms (e.g. common carotid involvement decr cerebral perfusion)
- Elevated ESR (inflamm → (+) particles → faster Rouleaux)
What is polyarteritis nodosa (and what organ does it conspicuously spare)?
Answer
A necrotizing vasculitis that spares the lungs
Wegener DDx:
PAN - "lung"-shaped hole
micro - "nose"-shaped hole
Card 139
In whom does polyarteritis nodosa typically present? How does it present (4 features)?
Answer
Typically presents in young adults as:
- hypertension (renal artery involvement)
- abdominal pain with melena (mesenteric artery involvement)
- neurologic disturbances
- skin lesions
*KEY: associated with HBV infection
Wegener DDx:
PAN - "lung"-shaped hole
micro - "nose"-shaped hole
Card 140
How do the lesions of polyarteritis nodosa evolve/progress?
Answer
Lesions of varying stages are present (*this is key).
Early lesions consist of transmural inflammation with fibrinoid necrosis.
Lesions heal with fibrosis, producing a "string-of-pearls" appearance on imaging (particularly in renal vasculature)
Distinguishing Features:
PAN - concentric (inflamm/fibrosis cycles), microaneurisms (fibrinoid necrosis)
fibromuscular dysplasia - fibrous thickening (dev defect)
Card 141
What is the treatment for polyarteritis nodosa?
Answer
Corticosteroids and cyclophosphamide
*Note - this disease is fatal if not treated
Card 142
What are the presenting features of Kawasaki disease (6)?
Answer
1) Child (usually asian) < 4 yrs old
2) Fever
3) Conjunctivitis
4) Erythematous rash of palms and soles (motorcycle; don't confuse with rickettsia)
5) Enlarged cervical lymph nodes
6) Strawberry tongue
Card 143
Coronary artery involvement in Kawasaki disease can lead to which two complications?
Answer
1) Thrombosis with MI
2) Aneurysm with rupture
Card 144
What is the treatment for Kawasaki disease?
Answer
Aspirin (counterintuitive! ASA quells fever; opposite response to Reyes, but similar flu-like Sx), and
IVIG (disables problematic anti-endothelial Abs, fast response)
Card 145
What is Beurger disease? How does it present?
Answer
A necrotizing vasculitis involving the digits (arteries and veins can both be affected)
Presents with ulceration, gangrene, autoamputation of fingers and toes. Raynaud phenomenon often present.
Card 146
What is the treatment for Beurger disease?
Answer
Smoking cessation
Card 147
What are the small-vessel vasculitides (4)?
Answer
1) Granulomatosis with polyangitis (Wegener grnaulomatosis)
2) Microscopic polyangitis
3) Churg-Strauss syndrome (Eosinophilic grnaulomatosis with polyangitis)
4) Henoch-Schönlein purpura
Card 148
What is granulomatosis with polyangitis? What structures/organs does it involve?
Answer
A necrotizing granulomatous vasculitis that involves the nasopharynx, lungs, and kidneys
Card 149
What is the classic presentation of granulomatosis with polyangitis? What serum maker is typically present? What will biopsy reveal?
Answer
A middle-aged male with:
- sinusitis or nasopharyngeal ulceration
- hemoptysis and bilateral nodular lung infiltrates
- hematuria (rapidly progressive glomerulonephritis)
c-ANCA levels (correlate with disease severity)
Biopsy reveals large necrotizing granulomas
Card 150
What is the treatment for granulomatosis with polyangitis?
Answer
Cyclophosphamide and steroids
Card 151
How can microscopic polyangitis be differentiated from granulomatosis with polyangitis (3)?
Answer
Though lung and kidney involvement is also a feature of microscopic polyangitis:
1) No nasopharyngeal involvement will be seen
2) No granulomas (no opacities in lung parenchyma on x-ray)
3) p-ANCA (rather than c-ANCA)
Wegener DDx:
PAN - "lung"-shaped hole
micro - "nose"-shaped hole
Card 152
What is the treatment for microscopic polyangitis? How effective is it?
Answer
Cyclophosphamide and steroids. Relapse is common.
Card 153
How does Churg-Strauss syndrome typically present (3)?
Answer
1) Necrotizing granulomatous inflammation typically involving lungs and heart.
2) Asthma and peripheral eosinophilia often present
3) p-ANCA positivity
Card 154
Who does Henoch-Schönlein purpura typically present in? What causes it?
Answer
Children.
It is caused by IgA immune complex deposition
*It is the most common vasculitis in children
Card 155
How does Henoch-Schönlein purpura typically present (4)?
Answer
1) Most often follows a URI
2) Palpable purpura on butt and legs
3) GI pain and bleeding
4) Hematuria (IgA nephropathy)
Card 156
What is the treatment for Henoch-Schönlein?
Answer
Steroids, but only treat if severe
Card 157
Systemic HTN is defined as what S/D pressure?
Answer
Greater than 140/90
Card 158
What percentage of HTN cases are primary (idiopathic) vs. secondary?
Answer
95%; 5%
Card 159
How does renal artery stenosis induce a secondary HTN?
Answer
1) Stenosis decreases blood flow to the glomerulus
2) Juxtaglomerular apparatus responds by secreting renin (converts ATogen to ATI)
3) ATI is converted to ATII by ACE
4) ATII raises BP by:
- contracting arteriolar smooth muscle
- promoting aldosterone release, increasing sodium retention in DCT
Card 160
What are three important causes of renal artery stenosis?
Answer
1) Atherosclerosis (in elderly males)
2) Fibromuscular dysplasia (in young females)
3) Polyarteritis nodosa (in young males/patients with HBV)
Distinguishing Features:
PAN - concentric (inflamm/fibrosis cycles), microaneurisms (fibrinoid necrosis)
fibromuscular dysplasia - fibrous thickening (dev defect)
Card 161
What is fibromuscular dysplasia?
Answer
Developmental defect in the blood vessel walls, which yields irregular thickening of large- and medium-sized arteries. Affects young females.
Distinguishing Features:
PAN - concentric (inflamm/fibrosis cycles), microaneurisms (fibrinoid necrosis)
fibromuscular dysplasia - fibrous thickening (dev defect)
Card 162
What is malignant HTN?
Answer
A blood pressue greater than 180/120, presenting with papilledema and end-organ damage
1) Endothelial dysfunction allows lipids to enter the intima
2) Lipids are oxidized and consumed by macrophages
3) Inflammation and healing leads to deposition of ECM and proliferation of smooth muscle.
Card 167
What are three chronic-ish conditions that result from atherosclerotic disease?
Hyaline arteriolosclerosis represents what pathological process?
Answer
Proteins leaking into the vessel wall as a consequence of longstanding benign hypertension/diabetes
Card 170
What are the sequelae of hyaline arteriolosclerosis?
Answer
End organ ischemia, most commonly arteriolonephrosclerosis, or glomerular scarring that slowly progresses to renal failure.
Card 171
What causes hyperplastic arteriolosclerosis? dz mech?
Answer
Usually a consequence of malignant hypertension (acute process) - represents hyperplasia of the smooth muscle wall.
Card 172
What is the classic consequence of hyperplastic arteriolosclerosis?
Answer
Acute renal failure with "flea-bitten" appearance.
Card 173
What is Mönckeberg sclerosis and what is the clinical significance?
Answer
Calcific, non-obstructive narrowing of the media of medium sized arteries.
Not clinically significant; usually an incidental finding.
Card 174
What is an aortic dissection?
Answer
Intimal tear with dissection of blood through the media of the aortic wall
Card 175
What 3 conditions might predispose towards aortic dissection? Dz mechs of each?
Answer
1) Hypertension leading to hyaline arteriolosclerosis of the vasa vasorum and subsequent atrophy of the media
2) Marfan syndrome
3) Ehlers-Danlos
*Both Ehlers-Danlos and Marfan are associated with cystic medial degeneration
A, Cross-section of aortic media from a patient with Marfan syndrome, showing elastin fragmentation and areas devoid of elastin that resemble cystic spaces but are actually filled with proteoglycans (asterisks). B, Normal media for comparison, showing the regular layered pattern of elastic tissue. In both A and B, elastin is stained black.
Card 176
What is the most common cause of death following an aortic dissection?
Answer
Pericardial tamponade (tear tracks down into the pericardium)
Card 177
A thoracic aneurysm with "tree-bark" appearance is indicative of what?
Answer
tertiary syphilis
Card 178
What is the major complication of aortic dilatation?
Answer
Aortic valve insufficiency
*Note that compression of mediastinal structures (trachea and esophagus) can also occur
Card 179
Abdominal aortic aneurysm is usually seen in what kind of patient?
Answer
Since it is primarily due to atherosclerosis, it is commonly seen in male smokers > 60 yrs.
Card 180
What is the major complication of an abdominal aortic aneurysm? Risk criterion?
Answer
Rupture - risk greatly increased when diameter exceeds 5 cm.
Card 181
What is a hemangioma? What organs can be involved?
Answer
A benign vascular tumor, typically present at birth, that regresses spontaneously during childhood.
Skin and liver.
Card 182
What is an angiosarcoma? What organs are most commonly involved?
Liver angiosarcoma is associated with what 3 exposures?
Answer
1) Polyvinyl chloride
2) Arsenic
3) Thorotrast (a radiocontrast agent)
Card 184
What is the classic finding on EKG for stable angina? How is stable angina relieved?
Answer
ST segment depression
Relieved by rest and nitroglycerin
Card 185
What is the classic finding on EKG for Prinzmetal angina? Treatment?
Answer
ST segment elevation due to transmural ischemia.
Treatment: nitroglycerin or calcium channel blockers (verapamil)
Pathophysiology:
coronary artery vasospasm
Card 186
What cardiac marker is useful for detecting reinfarction on top of an acute MI? When does it peak and how long does it remain detectable?
Answer
CK-MB
Peaks at 4-6 hrs, returns to normal by 72 hrs
Card 187
What cardiac marker is the gold standard for detecting an MI? When does it first become detectable, peak, and become no longer detectable?
Answer
Troponin I
Levels rise 2-4 hrs after infarct, peak at 24 hrs, returns to normal in 7-10 days.
Card 188
In the first 6 hrs of an MI, what is your best diagnostic tool?
Answer
EKG
Card 189
What are three severe complications that can occur 4-7 days post-MI?
Answer
rupture of ventricular free wall (leads to cardiac tamponade)
rupture of IV septum (leads to shunt creation)
rupture of papillary muscle (leads to mitral insufficiency)
Card 190
What is Dressler syndrome?
Answer
It is an autoimmune phenomenon resulting in fibrinous pericarditis. Occurs several weeks post-MI.
Card 191
What complication can occur 4-24 hours post-MI?
Answer
Development of a fatal arrhythmia (conduction system necrosis)
Card 192
Do "heart-failure cells" present with left- or right-sided heart failure? How do they form?
Answer
More common of left-sided heart failure.
These are hemosiderin-laden macrophages, which pick up hemosiderin from small, congested alveolar capillaries that burst.
Card 193
What is the most common cause of right-sided heart failure?
Answer
Left-sided heart failure
Card 194
What are three clinical features of right-sided HF?
Answer
1) Jugular venous distension
2) Painful hepatosplenomegaly with characteristic "nutmeg" liver
3) Dependent pitting edema ("dependent" means worse when upright)
Card 195
What 3 congential heart defects initially present with left-to-right shunting?
Answer
VSD, ASD, PDA
Card 196
What is the most common congenital cardiac anomaly? What syndrome is it associated with?
Answer
VSD; associated with Fetal Alcohol Syndrome
Card 197
What determines the degree of shunting in a VSD? How is VSD treated?
Answer
Size determines level of shunting - smaller defects are usually asymptomatic, larger ones typically progress to eisenmenger.
Large defects are closed surgically. Small defects are typically left alone (often close spontaneously).
Card 198
What type of heart defect is characterized by a loud S1 and a wide, fixed split S2?
What are the two types of ASD? What is significant about each?
Answer
Ostium secundum is the most common type overall;
Ostium primum is the most common type in Down syndrome
Card 200
What cardiac defect is associated with congenital rubella?
Answer
PDA
Card 201
PDA bypasses what part of the circulatory system?
Answer
The PDA is a left-to-right shunt between aorta and the pulmonary artery. Before birth - it serves as a right-to-left shunt that bypasses pulmonary circulation.
Card 202
PDA is known for what characteristic murmur?
Answer
A continuous "machine-like" murmur
Card 203
What drug is used to close a PDA?
Answer
Indomethacin (NSAID - blocks PGE2 production by COX)
Card 204
How does PDA typically present, clinically?
Answer
Lower extremity cyanosis in a child
Card 205
What are the components of tetralogy of fallot?
Answer
P: pulmonary stenosis (or stenosis of the pulmonary outflow tract)
R: Right ventricular hypertrophy,
O: Over-riding aorta
V: Ventricular septal defect
Card 206
What type of shunt does Tetralogy of fallot result in?
Answer
Right-to-left (presents with early cyanosis)
Card 207
What x-ray finding is classically associated with Tetralogy of Fallot?
Answer
A "boot-shaped" heart
Card 208
What congenital cardiac defect is associated with maternal diabetes?
Answer
Transposition of the great vessels (TGA)
Stupid and Desperate Memory Tip:
Twizzlers are off limits (aorticopulmonary septum's shape)
Card 209
What are the five right-to-left shunts that present with early cyanosis?
Answer
Truncus arteriosus (1 trunk)
Transposition of the great vessels (2 great vessels)
Tricuspid atresia (3 valve leaflets)
Tetralogy of fallot (4 things in tetralogy)
Total anomalous pulmonary venous return (TAPVR) (5 letters in TAPVR)
Card 210
What embryological problem results in a transposition of the great vessels?
Answer
Failure of the aorticopulmonary (aka spiral or conotruncal) septum to spiral
Card 211
What is the immediate post-birth treatment for an infant with transposition of the great vessels?
Answer
Patency of the PDA (to allow for intermixing between independent right and left circuits) has to be maintained. This can be done with prostaglandins or prostaglandin analogues (misoprostol, alprostadil).
Card 212
Describe the infantile form of coarctation of the aorta. What genetic abnormality is it associated with?
Answer
1) Associated with a PDA
2) Coarctation lies distal to aortic arch, proximal to the PDA
3) Presents with lower extremity cyanosis in children (deoxygenated blood shunted through the PDA distal to the coarctation)
Common finding in Turner Syndrome (45 XO). However, note that PERFECTLY GENETICALLY NORMAL infants can ALSO get infantile coarctation.
Card 213
Describe the clinical presentation of the adult form of coarctation of the aorta:
Answer
1) No associated PDA. Coarctation still exists distal to aortic arch
2) Hypertension in upper extremities, hypotension with weak pulses in lower extremities
3) Collateral circulations across the intercostal arteries cause "notched ribs" on imaging
4) Associated with bicuspid aortic valve
Memory Tip:
Pressure symptoms in two parts (abn pressures in both UE and LE; congenital form only has abn LE perfusion),
bicuspid valve has two flaps
Card 214
How are aortic stenosis caused by age and aortic stenosis caused by chronic rheumatic valve disease distinguishable?
Answer
Chronic rheumatic heart disease will commonly involve the mitral valve as well;
fusion of the aortic valve commisures is also a unique feature.
Card 215
Stable angina represents atherosclerotic occulusion of how much coronary artery?
Answer
>70%
Card 216
How does stable angina present?
Answer
Exertional chest pain lasting < 20 min that can radiate to the left arm or jaw. Can be accompanied by diaphoresis or shortness of breath.
Card 217
Unstable angina manifests from what pathological process?
Answer
Usually due to rupture of an atherosclerotic plaque with incomplete occlusion of a coronary artery.
Card 218
Is myocyte injury in unstable angina still reversible?
Answer
Yes
Card 219
What EKG findings do you expect in unstable angina?
Answer
ST-segment depression
Card 220
What is the most feared complication of unstable angina?
Answer
Progression to MI
Card 221
Other than plaque rupture and full coronary artery occlusion, what are 3 less common causes of MI?
Answer
1) Coronary artery vasospasm (due to cocaine use or Prinzmetal angina)
2) emboli (very rare)
3) vasculitis / aneurysm rupture (Kawasaki disease)
Card 222
What are the clinical features of an MI?
Answer
Severe, crushing chest pain ( > 20 min) that radiates to the left arm/jaw, diaphoresis, dyspnea; symptoms not relieved by nitroglycerin
*Friendly reminder that women are more likely to have an atypical presentation of MI - common would be epigastric abdominal pain
Card 223
What is the most commonly involved vessel in an MI?
Answer
The LAD - in both RCA- and LCA-dominant distributions
Card 224
What structures become ischemic in LAD infarction (3) ?
Answer
Anterior wall of the LV
Anterior portion of the interventiricular septum
Anterolateral papillary muscle
Card 225
What structures can become ischemic in an infarction of the RCA?
Answer
Posterior wall of LV
Posterior portion of interventricular septum
Posteromedial papillary muscle (or both papillary muscles)
Card 226
What structure becomes ischemic in an infarct of the LCX?
Answer
The lateral wall of the LV
*Important: if the patient has left dominant circulation (posterior descending artery arises from the LCX), then LCX infarct can also result in posterior wall/posteromedial papillary muscle ischemia)
Card 227
Describe the progression of EKG findings one would find if measuring right at the start of a STEMI MI:
Answer
1) Initial necrosis is subendocadial - while only <50% of the wall is infarcted, ST depressions will show
2) Once infarction progresses to become transmural, ST elevations will be observed
Card 228
Treatment for an MI can include what 6 therapies/therapeutic classes?
What are two general clinical sequelae of left-sided heart failure?
Answer
1) Pulmonary congestion leading to pulmonary edema (and all associated complications)
2) Decreased flow to kidney, which actives the RAA system causing fluid retention and exacerbation of HF symptoms
Card 240
What is the mainstay of treatment for left-sided heart failure?
Answer
ACEi
Card 241
When during embryogenesis do congenital heart defects typically arise?
Answer
Between 3-8 weeks (during organogenesis)
Card 242
What is the incidence of congenital heart defects?
Answer
1:100 births (1%)
Card 243
How do left-to-right shunts progress and present?
Answer
1) Increased flow through pulmonary circulation results in hypertrophy of pulmonary vessels and pulmonary hypertension.
2) Increased pulmonary resistance results in reversal of shunt (Eisenmenger syndrome), which presents with:
- cyanosis
- RV hypertrophy
- polycythemia
- clubbing
Card 244
How do congential right-to-left shunts typically present?
Answer
Early cyanosis.
Card 245
A paradoxical embolus (e.g. stroke occurs following DVT) is suggestive of what pathology?
Answer
Presence of an ASD - inadequate development of septum secundum (90%) or excessive loss of septum primum (5%)
*The presence of a patent foramen ovale (i.e. septum primum/secundum flap is closed, but not sealed) is more common than that of an ASD; either could cause a paradoxical embolus
Card 246
The degree of pulmonic stenosis influences what two factors in Tetrology of Fallot?
Answer
Degree of stenosis determines level of shunting and cyanosis (the more stenotic the pulmonary outflow tract is, the more blood is pushed through the VSD)
Card 247
How do Tetrology of Fallot patients typically respond to cyanotic spells?
Answer
They learn to squat - increases systemic resitance which reduces degree of shunt
Card 248
How are the ventricles affected in cases of transposition of the great vessels?
Answer
Right ventricle hypertrophies;
left ventricle atrophies
(They are each feeding the opposite of their intended circuits - left feeds low pressure pulmonary circulation, right feeds high pressure systemic)
Card 249
How is truncus arteriosus characterized?
Answer
By one large vessel arising from both ventricles
Card 250
Tricuspid atresia results in absent communication between the right atrium and right ventricle. What other defect is it typically associated with? What additional defect must be present for survival?
Answer
Tricuspid atresia is usually assoicated with an ASD.
VSD must also be present for survival (blood pumped from RA to LA through the ASD, from LA to LV, from LV to RV through VSD, out to lung circulation).
Card 251
Valvular lesions general result in what two valvular issues?
Answer
Stenosis or regurgitation
Card 252
How long following an episode of Group A β-hemolytic strep pharyngitis does acute rheumatic fever typically present?
Answer
2-3 weeks
Card 253
Describe the pathogenesis of acute rheumatic fever:
Answer
Bacterial M protein resembles cardiac muscle proteins - autoimmune response mounts by way of molecular mimicry
Card 254
What are the criteria for diagnosing Rheumatic Fever?
Answer
1) Evidence of prior GAS infection, and either
2a) Two major (JONES) criteria, or
2b) One major plus two minor criteria (nonspecific, e.g. fever, arthralgia, or elevated acute-phase reactants in serum)
Card 255
What are the JONES criteria (be detailed)?
Answer
1) Joints: migratory polyarthritis
2) ♥: Pancarditis, which consists of
- Endocarditis (mitral valve involvement most common)
- Myocarditis (Aschoff bodies and Anitschkow cells)
- Pericarditis
3) Nodules: Subcutaneous nodules
4) Erythema marginatum
5) Sydenham's chorea
Card 256
How can acute rheumatic fever progress?
Answer
Acute attack usually resolves, but may progress to chronic rheumatic heart disease. Re-infection increases likelihood of developing chronic disease.
Card 257
What is chronic rheumatic heart disease?
Answer
Valve scarring that arises as a result of rheumatic fever
Card 258
Classic "fish-mouth" appearance of heart valves is assoicated with what condition?
Answer
Chronic rheumatic heart disease
Card 259
What two valves are most commonly involved in chronic rheumatic heart disease? Specifically what gross changes can be appreciated?
Answer
1) Mitral valve: leads to thickening of the chordae tendinae and cusps
2) Aortic valve (less common): fusion of the commissures
Card 260
Describe the 3 typical etiologies of aortic valve stenosis:
Answer
1) Age-related fibrosis and calcification ("wear and tear"). Usually presents > 60 yrs.
2) Arising from wear and tear on a bicuspid aortic valve
3) As a consequence of chronic rheumatic valve disease
Card 261
How can one distinguish aortic stenosis due to chronic rheumatic valve disease from typical "wear and tear" aortic valve stenosis?
Answer
1) Co-involvement of the mitral valve
2) Fusion of the commissures
Card 262
Why does aortic stenosis remain undetected for a prolonged period?
Answer
Cardiac compensation delays development of noticable symptoms.
Card 263
What are 3 major complications of aortic valve stenosis?
Answer
1) Concentric left ventricular hypertrophy
2) Angina and syncope with exercise - limited bility to increase blood flow across the stenotic valve leads to decreased perfusion of the myocardium and brain
3) Microangiopathic hemolytic anemia - *"macroangiopathic" if you're looking at first aid
Card 264
What is the treatment for aortic stenosis?
Answer
Replacement, following onset of complications
Card 265
What are some common causes of aortic regurgitation?
What are the 5 clinical features of aortic regurgitation (murmur, circulatory changes, ventricular changes)?
Answer
1) Early, blowing diastolic murmur
2) Hyperdynamic circulation due to increased pulse pressure:
- bounding "water-hammer" pulse
- pulsating nail bed (Quincke pulse)
- head bobbing
3) LV dilitation/eccentric hypertrophy (volume overload)
Card 267
How does a bounding "water-hammer" pulse develop in aortic regurgitation?
Answer
Diastolic pressure decreases due to regurgitation;
systolic pressure increases due to increased stroke volume
Card 268
What is mitral prolapse?
Answer
Ballooning of mitral valve into the left atrium during systole
Card 269
What % of US adults have mitral valve prolapse?
Answer
2-3%
Card 270
What is the pathological change that causes mitral prolapse?
Answer
Myxoid degeneration - accumulation of ground substance on the valve, making it floppy
Card 271
In what two genetic conditions is mitral prolapse commonly seen?
Answer
Marfan syndrome and Ehlers-Danlos
Card 272
What is the typical murmur heard in mitral prolapse and what maneuver makes it softer/louder?
Answer
Mid-systolic click followed by a regurgitation murmur
Becomes softer with squatting
Card 273
What are the complications of mitral stenosis? What is the treatment?
Answer
Complications are rare, but include:
arrhythmia (most commoly a-fib),
systemic embolism (due to thrombus),
infective endocarditis (< 1% IE is due to mitral stenosis),
and progression to tricuspid regurgitation (pulmonary congestion → R heart volume overload)
Treatment is valve replacement.
*Rheumatic heart disease (RHD) can result in both mitral stenosis (MS) and regurgitation (MR) (think about the fish mouth being "locked" in a semi-open position). However, MR in advanced disease is not a complication of MS; the etiology of the MR is RHD.
**Changes to this flashcard were based on Braunwald Ch 63
Card 274
What are the clinical features of mitral stenosis (murmur, LA/pulmonary effects)?
Answer
1) Opening snap with diastolic rumble (large diastolic pressure gradient → turbulent flow → audible "rumble")
2) Volume overload leads to dilitation of the LA, resulting in:
- Pulmonary congestion with edema and alveolar damage
- Pulmonary hypertension and right-sided heart failure
- Atrial fibrillation and risk of mural thrombi
*Important concept: whenever you dilate heart tissue, you increase the risk of developing an arrythmia
Card 275
What is most common overall cause of infective endocarditis?
Answer
Step viridans
Card 276
What is the pathophysiology of vegetation development in the instance of an S. viridans infection?
Answer
1) Damaged endocardial surface develops thrombotic vegetations (platelets and fibrin)
2) Transient bacteremia leads to trapping of bacteria in the vegetations
Card 277
What is the difference between "acute" and "subacute" endocarditis?
Answer
Acute endocarditis is obliterative (damages the valve), whereas
subacute endocarditis does not disrupt valve architecture.
Card 278
S. aureus, S. bovis, S. epidermidis: what patients are associated with endocarditis caused by each?
Answer
S. aureas: tricuspid endocarditis in IV drug abusers
S. bovis: endocarditis in patients with underlying colorectal carcinoma
S. epidermidis: endocarditis of artificial valves
Memory Tip:
Eating beef ("bovis") increases the risk of developing colorectal cancer
Card 279
What are the HACEK organisms and what do they cause?
Answer
Haemophilus, Actinobacillus (Aggregatibacter), Cardiobacterium, Eikenella, Kingella.
Associated with blood culture (-) endocarditis
Sketchy-Wannabe Memory Tips:
Haemophilus - "heme," i.e. the blood
Actinobacillus - sounds like Actinomyces, but not
Cardiobacterium - what else could Cardio be?
Eikenella - Ike ("eik") from Fire Emblem/SSBM "and" the creepy Cinder("ella")
Kingella - Ella killed Ike to become King Ella (sorry, Disney)
Aggregatibacter - the new "A" in HACEK, messed up the name just like how Aggron the Pokemon ruined the picture
Card 280
What are the clinical features of bacterial endocarditis (4)?
1) Nonbacterial thrombotic endocarditis consists of sterile vegetations that
2) arise from a hypercoagulable state/underlying adenocarcinoma
3) Vegetations arise on mitral valve along lines of closure and
4) result in mitral regurgitation
Card 282
Describe Libman-Sacks endocarditis. What valve defect will it lead to?
Answer
Sterile vegetations that arise in patients with SLE.
They characteristically arise on both sides of the valve.
Results in mitral regurgitation.
Card 283
Does DCM result in heart failure with systolic or diastolic dysfunction? What are some common complications of biventricular dilation?
Answer
Systolic dysfunction
cardiomyocytes in series → decreased inotropy (compliance, i.e. ∆V/∆P, is not the main issue)
Mitral/tricuspid regurgitation and arrhythmia can result from dilation.
*A general schema in your head should be that dilitations of the heart anatomy can cause valvular insufficiency
Card 284
What are the 7 major causes of DCM?
Answer
1) Idiopathic (most common)
2) Myocarditis (most associated with Coxsackie A or B)
3) Alcohol abuse (metabolites/toxins, nutrient deficiencies, and ETC impairment cause cell injury/fibrosis)
4) Drugs (doxorubicin)
5) Pregnancy (angiogenic imbalance)
6) Hemochromatosis
7) Genetic mutation (structural - AD inheritence)
Card 285
Hereditary HCM is usually due to mutations in what kind of protein?
Answer
Sarcomere proteins
Card 286
What are the clinical features of HCM (3)?
Answer
1) Decreased cardiac output:
parallel cardiomyocytes → decreased compliance (no inotropy issues)
hypertrophy → outflow tract obstruction
2) Sudden death due to spontaneous ventricular arrhythmias (widened QRS)
3) Syncope with exercise - hypertrophy of the the ventricular septum results in functional aortic stenosis
Card 287
What does biopsy of HCM show?
Answer
Myofiber hypertrophy with disordered growth
Card 288
How does restrictive cardiomyopathy typically present? What specific EKG abnormality might be present?
Answer
Decreased compliance of the ventricular endomyocardium restricts filling during diastole (diastolic dysfunction).
Presents as CHF - less energy output (i.e. decreased PV integral) → insufficient systemic perfusion and congestion
EKG can show low voltage QRS - loss of viable myocardium
DDx:
constrictive pericarditis - Kussmaul sign; absent in restrictive cardiomyopathy
Mesenchymal tumor (benign) that occurs in adults (most common primary cardiac tumor in adults).
Card 291
What finding is characteristic of myxoma on histological examination?
Answer
Abundant ground substance
Card 292
How does a myxoma cause symptoms?
Answer
Usually forms a pedunculated mass in the LA that causes episodic syncope as it obstructs the mitral valve.
Card 293
What is the most common primary cardiac tumor of the heart in children? What condition is it associated with? Where does it commonly arise?
Answer
Rhabdomyoma - a benign hamartoma of cardiac muscle.
It is associated with tuberous sclerosis
Arises in the ventricle
Card 294
What is the most common tumor of the heart?
Answer
Metastasis
Card 295
What are the most common heart mets? How do they usually present?
Answer
Breast and lung carcinoma, melanoma, lymphoma.
Typically involve the pericardium, resulting in pericardial effusion.
Card 296
What is this?
Answer
Aschoff body (common finding of acute rheumatic fever)
Card 297
What are these?
Answer
Anitschkow cells - associated with acute rheumatic fever
Card 298
What is this?
Answer
Fusion of aortic commisures - seen in chronic rheumatic valvular disease
Card 299
This gross specimen demostrates what pathology?
Answer
Endocardial fibroelastosis (a cause of RCM in children) - fibroelastic thickening, typically involves LV endocardium
Card 300
A child presents with nasal polyps - what diseases should he be worked up for (2)?
Answer
1) Cystic fibrosis
2) Aspirin-intolerant asthma
Card 301
What is the triad of aspirin-intolerant asthma?
Answer
"Samter's triad": Asthma, aspirin-induced bronchospasms, and nasal polyps.
Seen in 10% of adult asthmatics
Card 302
In what population are angiofibromas classically seen? What is the classic presentation?
Answer
Adolescent males; profuse epistaxis
*May be associated with Tuberous Sclerosis
Card 303
A Chinese adult male presents with large cervical lymph nodes and masses in the nasopharynx. Biopsy reveals pleomorphic keratin-positive epithelial cells in a background of lymphocytes. Diagnosis? Who else might this disease present in?
Answer
Nasopharyngeal carcinoma (associated with EBV);
African children
In contrast to Burkitt lymphoma, 100% of nasopharyngeal carcinomas obtained from all parts of the world contain EBV.
Note: pathogenesis does NOT involve t(8:14) c-myc oncogene activation
Card 304
Most common cause of acute epiglottitis?
Answer
H. flu, serovar B
Card 305
Most common cause of laryngotracheobronchitis (croup)?
Answer
Parainfluenza virus
Card 306
What causes laryngeal papilloma (a benign tumor of the vocal cord)?
Answer
HPV 6 and 11;
Card 307
What is the difference in presentation of laryngeal papilloma in adults vs. children?
Answer
Presents as a single papilloma in adults and as multiple in children
Card 308
What are the risk factors for laryngeal carcinoma?
Answer
Alcohol and tobacco; rarely can arise from laryngeal papilloma
Card 309
What are the two key molecular mediators of pain?
Answer
Bradykinin and PGE2
Card 310
What are the two most common causes of lobar pneumonia?
Answer
Strep pneumoniae and Klebsiella pneumoniae
Card 311
A lobar pneumonia in a patient with increased risk for aspiration is suspicious for what organisms (4)?
Answer
1) Klebsiella pneumoniae. Common in alcoholics and hospitalized (esp. intubated and comatose) patients. *Remember - "currant jelly sputum"
2) Anaerobic enteric bacteria
- Bacteroides
- Fusobacterium
- Peptococcus
Card 312
What are the functions of type I and II pneumocytes?
Answer
Type I: extremely thin, make up majority of alveolar surface area
Type II: produce surfactant, act as the alveolar epithelial stem cells
Card 313
What are the gross phases of lobar pneumonia? Describe each:
Answer
1) Congestion - due to congested vessels and edema
2) Red hepatization - exudate, neutrophils, and hemorrhage fill the the alveolar air spaces, creating a red, solid, "liver like" consitency to the lung tissue
3) Gray hepatization - red cells within exudate are degraded
4) Resolution - Type II pneumocytes (stem cells) regen lining of alv air sacs
Card 314
Describe the radiologic appearance of bronchopneumonia:
Answer
Scattered patchy consolidation that is centered around bronchioles; often multifocal and bilateral.
Card 315
What are the 5 most common causes of bronchopneumonia and what disease processes are each organism associated with?
Answer
1) Staph Aureus - seen post-URI (superinfection)
2) H. flu - seen post-URI and as pneumonia superimposed over COPD
3) Pseudomonas - seen in cystic fibrosis patients
4) Moraxella catarrhalis - community acquired pneumonia, also as pneumonia superimposed over COPD
5) Legionella - community acquired, COPD, immunocompromisation
Card 316
What is the most common cause of interstitial (atypical) pneumonia? Who is most at risk?
Common complications (2)?
Answer
Mycoplasma.
Young people living in barracks or college dorms.
Cold-agglutinin autoimmune hemolytic anemia, erythema multiforme.
Card 317
Most common cause of interstitial (atypical) pneumonia in infants?
Answer
Respiratory Syncytial Virus
Card 318
What is the most common cause of interstitial (atypical) pneumonia in patients taking post-transplant immunosuppressive therapy?
Answer
Cytomegalovirus
Card 319
Which lobe is most commonly involved in cases of aspiration pneumonia?
Answer
Right lower lobe - anatomically the path of least resistance.
Card 320
Compare primary TB and secondary TB in terms of:
Initiating factors
Location
Characteristic lesions/gross pathological features
Symptoms
Answer
Primary TB:
Initial infection
located at lung bases
Focal caseating necrosis, hilar involvement and calcification (Ghon complex)
Clinically asymptomatic
Secondary TB:
Immunosupression (AIDS, aging etc)
Located in apex
Caseating cavitary lesion
Fever, night sweats and hemoptysis (cough blood), systemic dissemination
Card 321
What are the key spirometry readings for chronic obstructive pulmonary disease?
TLC:
FEV1:
FVC:
FEV1/FVC ratio:
What is the definiton of chronic bronchitis? What is it highly associated with?
Answer
Productive cough lasting at least 3 months, over a minimum of 2 years
Highly associated w/ smoking.
Card 323
What is the Reid index? What is diagnostic value for chronic bronchitis?
Answer
Ratio of mucus gland thickness to overall bronchial wall thickness.
In chronic bronchitis, Reid index > 50%
normal < 40%
Card 324
What type of cell undergoes hypertrophy in chronic bronchitis?
Answer
Bronchial mucinous glands, yielding an increased Reid index
Card 325
4 clinical features of chronic bronchitis:
Answer
1) Productive cough due to excess mucus production
2) Cyanosis (blue bloaters) - mucus plugs trap CO2 leading to ↑ PaCO2 and ↓PaO2
3) Increased risk of infection (blocked tube)
4) Cor pulmonale (R heart failure due to pulmonary HTN)
Card 326
What is the underlying physical/functional pathophys of emphysema?
Answer
Loss of alveoli elastic recoil leads to collapse of airways during exhalation which causes obstruction and air trapping.
Card 327
Emphysema is caused by an imbalance of proteases and antiproteases. What are the 2 most common causes, and how do they create these imbalances?
Answer
1) Smoking: induces lung inflammation. Nφ and Mφ induced to release higher levels of connective tissue proteases. α₁AT unable to compensate (centriacinar)
2) α₁ antitrypsin deficiency: mutated misfolded α₁AT accumulates in the RER of hepatocytes, never making it to the lungs. (panacinar)
Card 328
What type of emphysema does alpha-1 antitrypsin (A1AT) deficiency result in?
Answer
Panacinar emphysema
Card 329
What is the most common clinically relevant mutation causing A1AT deficiency? How do heterozygotes and homozygotes present?
Answer
"PiZ" is the mutant a1-AT allele, "PiM" being the wild type.
PiMZ heterozygotes are typically asymptomatic, thought significant risk fro developing empysema exists if smoking is initiated.
PiZZ homozygotes are at baseline high risk for panacinar emphysema and liver cirrhosis (liver biopsy revelas pink, PAS+ globules of accumulated protein in hepatocytes)
Card 330
5 clinical features of emphysema:
Answer
1) Dyspnea and cough with minimal sputum
2) Prolonged expiration with pursed lips (pink puffer)
3) Weight loss
4) Barrel chest
5) Hypoxemia (cor pulmonale from constant pulmonary artery constriction can be a late complication)
Card 331
What are 2 key histopathological findings in the sputum of asthmatics?
Bronchiectasis is caused by necrotizing inflammation to airway walls, due to:
1) Cystic fibrosis
2) Kartagener syndrome
3) Tumor
4) foreign body
5) Necrotizing infection
6) Allergic bronchopulmonary aspergillosis (T1HSR to aspergillus)
What are the key spirometry reading for restrictive diseases?
TLC:
FEV1:
FVC:
FEV1/FVC ratio:
Answer
TLC: ↓
FEV1: ↓
FVC: ↓↓
FEV1/FVC ratio: ↑
Card 336
What is the key cytokine involved in the pathogenesis of idiopathic pulmonary fibrosis?
Answer
Cyclical lung injury results in TGF-β release from injured pneumocytes, which induces fibrosis.
Card 337
The patient from whom this lung specimen was taken likely had what disease?
Answer
Idiopathic pulmonary fibrosis - this is the classic "honeycomb lung" seen in late stage disease.
vs. bronchiectasis: dilation of bronchi/bronchioles, not interstitium
What is the only pneumoconiosis that increases the risk for tuberculosis infection?
Answer
Silicosis
Card 342
Differential diagnosis for noncaseating granulomas in the lung, hilar lymph nodes and systemic organs?
Answer
Sarcoidosis or berylliosis
(pick berylliosis if patient is a beryllium miner or a worker in the aerospace industry)
Card 343
What is a ferruginous body?
Answer
Long golden brown fibers with associated iron; confirms exposure to asbestos
Card 344
Any disease involving noncaseating granulomas can induce hypercalcemia. Why?
Answer
Noncaseating granulomas possess epithelioid histiocytes with 1-alpha-hydroxylase activity, which converts Vitamin D to its active form, inducing increased calcium uptake
Card 345
How is pulmonary HTN defined?
Answer
High pressure in the pulmonary circuit; MAP > 25 mm Hg; normal is 10 mm Hg
Card 346
Plexiform lesions are characteristic of what?
Answer
Longstanding pulmonary HTN.
Card 347
What is the gene that is classically associated with familial forms of primary pulmonary HTN? What does it do?
Answer
Inactivating mutation of BMPR2: leads to proliferation of vascular smooth muscle
Memory Tip:
Cars "bumper-to-bumper" give you high blood pressure. Can't breathe!
Card 348
What is the hallmark of acute respiratory distress syndrome (ARDS)? How do they arise?
Answer
Hyaline membranes; made of protein-rich fluids and necrotic epithelial cells
Card 349
What are the 2 key treatments for ARDS?
Answer
1) Treat underlying cause
2) Ventilation with positive end-expiratory pressure (PEEP)
Card 350
What immune cell is key to the pathogenesis of ARDS and what does it do? List some initiating causes of ARDS:
Answer
Activation of neutrophils induces protease-mediated/free radical damage of type I and II pneumocytes.
Caused by sepsis, infection, shock, pancreatitis, aspiration, DIC, hypersensitivity reactions, drugs, etc.
Card 351
Recovery from ARDS may be complicated by what? Why does this happen?
Answer
Interstitial fibrosis. Damage and/or loss of type II pneumocytes impairs lung regeneration/recovery, instead resulting in scarring and fibrosis
Card 352
What is the main component of surfactant? (& other name)
Answer
Phosphatidylcholine (Lecithin)
Card 353
What happens to the amniotic lecithin:sphingomyelin ratio as the fetal lungs mature? What is the target ratio?
Answer
Lecithin increases (since more surfactant is being produced) and sphingomyelin remains constant, so the ratio increases.
A ratio of > 2 indicates adequate surfactant production.
Card 354
What are 3 factors that neonatal respiratory distress syndrome (NRDS) is associated with?
Answer
1) Prematurity: adequate surfactant production is reached until 34 weeks
2) Caesarian section delivery: lack of stress-induced steroids. Steroids increase surfactant synthesis. Betamethasone used to stimulate surfactant production in women at-risk for premature delivery.
3) Maternal diabetes: insulin decreases surfactant production
Card 355
What are the 2 key mutagens found in cigarette smoke?
Answer
Polycyclic aromatic hydrocarbons and arsenic
Card 356
What are 3 exposures that greatly increase risk of developing lung cancer?
Answer
Cigarette smoke, radon, and asbestos
Card 357
What is the key finding on imaging for lung cancer? What does the subsequent work-up entail?
Answer
Solitary nodule known as a "coin-lesion".
Work-up entails:
Comparison with previous radiographs to look for changes
Biopsy (necessary for diagnosis)
Card 358
What are two non-cancer causes of "coin lesions" seen on X-ray?
Answer
1) Granuloma - often TB or Histoplasmosis
2) Bronchial hamartoma - benign tumor made up of lung tissue and cartilage, often calcified, often seen in context of tuberous sclerosis
*Note, a "hamartoma", by definition, is a tumor composed of disorganized but appropriate tissue for the organ in which it arises.
Memory Tip:
Both involve "tubers" in the lung--TUBERculosis, and TUBERous sclerosis.
Card 359
What are the 3 paraneoplastic syndromes associated with small cell carcinoma of the lung?
Which neuroendocrine cells does small cell carcinoma stem from?
Answer
"Kulchitsky" cells
cool shit: SCC can have multisystemic (endocrine) effects
Card 361
What is the paraneoplastic syndrome associated with squamous cell carcinoma of the lung?
Answer
Parathyroid hormone related protein (PTHrP) production, leading to hypercalcemia
Card 362
What are 2 characteristic histological features of squamous cell carcinoma of the lung?
Answer
Keratin pearls, intercellular bridges
Card 363
What is the most common tumor in non-smokers as well as in female smokers?
Answer
Adenocarcinoma
Card 364
What is the location of the following lung tumors: small cell, squamous cell, adenocarcinoma, large cell, bronchioloalveolar carcinoma?
Answer
small cell: central
squamous cell: central
adenocarcinoma: peripheral,
large cell: central or peripheral
bronchioloalveolar carcinoma: peripheral
Card 365
Which lung cancer classically presents as a pneumonia-like consolidation on imaging (and has an excellent prognosis)?
Answer
Bronchioloalveolar carcinoma
Card 366
Which type of cell does a bronchioloalveolar carcinoma arise from? What is that cell's function?
Answer
Clara cells (AKA "club cells") - bronchiolar exocrine cells. Involved in lysozyme production and IgA secretory component production.
Card 367
Which lung tumor is chromogranin positive?
Answer
Carcinoid tumor
Card 368
Which type of lung tumor classically forms a polyp-like mass in the bronchus?
Answer
Carcinoid tumor
Card 369
What is more common to the lung: primary tumor or metastasis?
Answer
Metastasis
Card 370
To where does lung cancer most commonly metastasize?
Answer
Adrenal glands
Card 371
Which two lung cancers are not in any way related to smoking?
Answer
Bronchioloalveolar carcinoma (adenocarcinoma) and carcinoid tumor
Card 372
What is a Pancoast tumor and what can it cause?
Answer
A tumor in the apex of the lung. It can cause Horner's syndrome (ptosis, miosis, anhydrosis) and thoracic outlet syndrome (compression of lower trunk of brachial plexus, edema of arm)
Card 373
What type of pneumothorax shifts the trachea to the side of the collapse?
Answer
Spontaneous pneumothorax (hole causes communication between lung parenchyma and pleural space)
Card 374
What type of pneumothorax shifts the trachea to the opposite side of the collapse?
Answer
Tension pneumothorax
Card 375
What does mesothelioma present with (3 symptoms)?
Answer
It presents with recurrent pleural effusions, dyspnea, and chest pain
Card 376
Diagnosis?
Answer
Vocal cord nodules (note - commonly bilateral)
Card 377
Type of pneumonia?
Answer
Lobar pneumonia
Card 378
Type of Pneumonia?
Answer
Lobar. Most commonly due to S. pneumoniae.
Air sacs full of neutrophils and exudate (pink froth)
Card 379
Type of pneumonia?
Answer
Bronchopneumonia
Card 380
What type of pneumonia?
Answer
Interstitial Pneumonia
Card 381
What type of pneumonia?
Answer
Interstitial. Air sacs are empty, inflammtory infiltrate contained to interstitium
Card 382
What organism can be seen in this specimen stained with an AFB stain?
Answer
M. tuberculosis
Card 383
What pathology is this histological specimen taken from the lung indicative of?
Answer
Idiopathic Pulmonary Fibrosis
Card 384
What is depicted in the histology specimen taken from the lung seen below? What disease would this be found in?
Answer
This is an asteroid body, typically seen in sarcoidosis
Card 385
What can be seen on this histological specimen taken from the lung? Underlying disease?
Answer
Plexiform lesions. Pulmonary Hypertension.
Group of capillaries placed together that arise as complication of longstanding pulm htn
Card 386
What is this?
Answer
Hyaline membranes seen in Acute Respiratory Distress Syndrome
Card 387
This radiograph is characteristic of what condition?
Answer
Acute Respiratory Distress Syndrome. Diffuse "white out" of the lung
Card 388
What condition might this radiograph be indicative of?
Describe the overall general pathogenesis of asthma:
Answer
1) Exposure to allergen with subsequent Th2 CD4+ immune response
2) Th2 cytokines recruit eosinophils
3) Re-exposure to allergen induces histamine release and generation of leukotrienes
4) Leukotrienes cause acute bronchoconstriction
5) Inflammation mediated by major basic protein perpetuates bronchoconstriction in the long term.
Card 415
What is the treatment for idiopathic pulmonary fibrosis?
Answer
Lung transplantation
Card 416
What are some causes of secondary pulmonary fibrosis?
In silicosis, where do fibrotic nodules typically form?
Answer
Upper lobes of the lungs
Card 422
4 clinical features/lab values of sarcoidosis:
Answer
1) Dyspnea and cough
2) Elevated serum ACE
3) Hypercalcemia (1α-hydroxylase in epithelioid histiocytes)
4) Can Rx steroids, but often spontaneously resolves
Card 423
What 3 processes lead to artery thickening in cases of pulmonary hypertension?
Answer
1) Atherosclerosis of pulmonary trunk - htn is a risk factor for atherosclerosis
2) Smooth muscle hypertrophy of pulmonary arteries - increased stress (htn) → hypertrophy
3) Intimal fibrosis - result of dmg/heal cycles
Card 424
What are the cardiac sequelae of pulmonary hypertension?
Answer
1) RV hypertrophy (hypertrophy due to stress, i.e. incr pressure)
2) Cor pulmonale (R heart failure due to pulmonary HTN)
Card 425
What are 3 causes of secondary pulmonary HTN?
Answer
1) Longstanding hypoxemia (pulm vasoconstr e.g. due to COPD or intersitital lung disease)
2) Heart disease (incr pulm vol, e.g. left-sided heart failure, congenital heart disease)
3) Recurrent pulmonary embolism (reorganize w/ thick vasc wall)
Card 426
What is the most common lung tumor in male smokers?
Answer
Squamous cell carcinoma
Card 427
Into what 2 general categories is lung carcinoma typically divided? How do these classifications affect treatment?
Answer
1) Small cell carcinoma: usually not amenable to surgical resection, therefore treated with chemo
2) Non-small cell carcinoma: treated up front with surgical resection, as they respond poorly to chemo
NSCLC is further broken down into: adenocarcinoma, sqaumous cell carcinoma, large cell carcinoma, and carcinoid tumor
Card 428
Pleural involvement is classically seen with which lung tumor?
Answer
Adenocarcinoma, or less commonly, mesothelioma. Adenoma will present as an invading mass, whereas mesothelioma will ensheathe the entire lung.
Card 429
What is superior vena cava syndrome?
Answer
Lung tumor located centrally (near mediastinum) compresses the SVC, leading to distended neck veins, edema, blue discoloration of arms and face.
Sx* appear/worsen when arms raised over head - positive Pemberton's sign.
*incl facial plethora, cyanosis, dyspnea, cough, stridor
Card 430
What two nerves can be involved with a central lung tumor?
Answer
Recurrent laryngeal (leading to hoarseness)
Phrenic (leading to diaphragmatic paralysis)
Card 431
Does lung cancer often present early or late?
Answer
Late. This likely contributes to the high mortality rate (15% 5 year survival)
Card 432
How does a spontaneous pneumothorax commonly arise, and in whom?
Answer
Spontaneous rupture of an emphysematous bleb - usually seen in young adults.
Card 433
How does a tension pneumothorax arise?
Answer
Penetrating wound to the chest wall
Card 434
Why does cleft palate occur?
Answer
Failure of facial prominences to fuse.
Card 435
What syndrome presents with a triad of recurrent aphthous ulcers, genital ulcers, and uveitis?
Answer
Behçet syndrome, which is believed to be caused by a small vessel immune vasculitis
Card 436
Cold sores are typically a result of HSV-1 laying dormant in what location?
Answer
The trigenimal nerve ganglia
Card 437
What are the two major risk factors for developing squamous cell carcinoma of the oral mucosa?
Answer
Tobacco and alcohol use
↑
Card 438
What are the etiological and anatomical differences in presentation between leukoplakia and oral hairy leukoplakia?
Answer
Leukoplakia (and erythroplakia) are precursor lesions to the development of oral squamous cell carcinoma, typically a sequela of tobacco/alcohol overuse, and typically present on the floor of the mouth.
In contrast, hairy leukoplakia (besides being "hairy-er"), typically arises on the lateral tongue, and is caused by an EBV-induced hyperplasia in the context of immunocompromisation. It is NOT metatstatic.
Card 439
Between erythroplakia and leukoplakia, which is more strongly suggestive of malignant/premalignant squamous cell dysplasia?
Answer
Erythroplakia. The redness suggests vascular involvement
Card 440
What are four potential clinical features of mumps infection?
What is the most common benign tumor of the salivary glands? What is its composition?
Answer
Pleomorphic adenoma, which is composed of stromal (cartilage) and epithelial tissue
Card 442
A patient has had a parotid mass for many years. He presents to clinic with recent-onset of facial nerve palsy symptoms. What is the most likely explanation for this clinical picture?
Answer
Facial nerve palsy is a sign of carcinoma invading the facial nerve. This man likely had an untreated pleiomorphic adenoma that transformed into carcinoma (a rare complication).
Card 443
What is the second most common benign tumor of the salivary gland? What might one see on histology?
Answer
Warthin tumor, usually arising in the parotid gland
Cystic tumor with abundant lymphocytes and germinal centers (lymph node tissue)
Card 444
What is the most common malignant tumor of the salivary glands? What is its composition? Where does it typically arise?
Answer
Mucoepidermoid carcinoma;
Composed of both mucinous and squamous cells;
Arises in the parotid gland.
Card 445
What is the most common variant of tracheoesophageal fistula?
Answer
Proximal esophageal atresia with the distal esophagus arising from the trachea.
Card 446
How will an infant with tracheoesophageal fistula (specifically, proximal atresia with distal fistula) present?
Answer
Presents with:
vomiting - undigested food trapped in upper esophagus
Polyhydramnios (in utero) - normally, the infant swallows amniotic fluid, this is not possible with blind-end upper esophageal pouch
Abdominal distension - air from trachea is diverted through TE fistula into the GI tract
Aspiration - contents of GI stomach pass through TE fistula into respiratory tract
*Note that cyanotic spells result from laryngospasm secondary to acid aspiration
Card 447
What is the classic triad of Plummer Vinson syndrome?
Answer
Dysphagia, Iron deficiency anemia, Esophageal webs
*Note that a beefy red tongue is a common symptom
"Plumbers DIE"
Card 448
Where does a Zenker diverticulum typically arise?
Answer
Arises above the upper esophageal sphincter at the junction of the esophagus and pharynx
Card 449
What is Mallory-Weiss syndrome? What causes it?
Answer
Longitudinal laceration of mucosa at the GE junction
Caused by severe vomiting (alcoholism and bulimia)
Card 450
What is Boerhaave syndrome? What predisposes towards its development?
Answer
Rupture of the esophagus leading to air in the mediastinum and subcutaneous emphysema
Mallory-weiss syndrome strongly predisposes towards developing Boerhaave syndrome
Card 451
Between Mallory-Weiss syndrome and esophageal varices, which presents with painful hematemesis and which presents with painless hematemesis?
What is the most common cause of death in patients with severe liver cirrhosis?
Answer
Rupture of esophageal varices
Card 453
What is the etiology of achalasia?
Answer
Achalasia represents damage to the ganglion cells of the myenteric plexus.
Achalasia can either be idiopathic or caused by Trypanosoma cruzi (Chagas disease)
Card 454
What are the 4 clinical signs of achalasia?
Answer
Dysphagia for both solids and liquids
Putrid breath
High LES pressure on esophageal manometry
Bird-beak sign on barium swallow study
*Accumulation of material at base of esophagus can also cause chest discomfort
Card 455
In contrast to Barrett esophagus, which predisposes towards the development of _____carcinoma, achalasia and esophageal webs predispose one towards developing ________ ______ carcinoma.
Answer
Barrett esophagus predisposes towards the development of adenocarcinoma, whearas achalasia and webs predispose towards squamous cell carcinoma.
*Both are types of esophageal carcinoma.
Card 456
What causes GERD?
Answer
Reflux of acid from the stomach due to reduced tone in the lower esophageal sphincter
Metaplasia of the lower esophageal mucosa from stratified squamous epithelium to non-ciliated columnar epithelium w/ goblet cells
*A common mistake is to think of Barrett esophagus as metaplastic change from esophageal to gastric epithelium. This is wrong. Examiners will consider Barrett esophagus as being a transition from esophageal epithelium to intestinal epithelium.
Card 459
What is the most common esophageal cancer worldwide? In the west?
Answer
Worldwide: squamous cell carcinoma
West: adenocarcinoma
*Remember it this way: adenocarcinoma comes from a shitty fatty diet. In the west, we're all super fat. So we get adenocarcinoma.
Card 460
What are the six risk factors for developing esophageal squamous cell carcinoma?
Answer
1) alcohol
2) tobacco
3) very hot tea (regions of iraq and iran)
4) achalasia
5) esophageal web
6) esophageal injury (lye injury)
Card 461
What is the one risk factor for developing adenocarcinoma of the esophagus?
Answer
Barrett esophagus
Card 462
Which regions of the esophagus do squamous cell carcinoma and adenocarcinoma of the esophagus arise in, respectively?
Answer
Squamous cell carcinoma: upper 2/3 of the esophagus
Adenocarcinoma: lower 1/3 of the esophagus
Card 463
Which lymph nodes will be involved in the instance of a carcinoma of the upper, middle, and lower thirds of the esophagus?
Answer
Upper: cervical nodes
Middle: mediastinal or tracheobronchial nodes
Lower: celiac and gastric nodes
*Note: this is super high yield
Card 464
What are the physical and etiological differences between gastroschisis and omphalocele?
Answer
Gastrochisis is caused by a failure of the anterior abdominal wall (the "lateral folds") to properly fuse, resulting in complete exposure of the abdominal contents.
By contrast, omphalocele is caused by failure of herniated intestines (normal step in development) to return to the body cavity, resulting in abdominal contents that are outside the cavity, but covered by peritoneum and the amnion of the umbilical chord.
Card 465
When do symptoms of pyloric stenosis commonly develop? What are these symptoms?
Answer
It normally presents about 2 weeks after birth.
Classic symptoms are:
Projectile nonbilious vomiting
Visible peristalsis (intestine that is distal to stenosis writhes so much that it is grossly visible)
Olive-like mass in abdomen (the stenotic pyloric sphincter)
Card 466
What is the difference in pathophysiology between a Curling ulcer and a Cushing ulcer? Both of these pathologies are risk factors for what?
Answer
Curling ulcer: caused by hypovolemia in the context of severe burns. Reduced plasma volume leads to ischemia and necrosis (sloughing) of the gastric mucosa
Cushing ulcer: caused by increased cranial pressue; stimulation of vagus nerve increases acid production and subsequent ulceration
Both predispose towards acute gastritis.
*Important to note that Curling ulcers can result in gastric perforation and hemorrhage, which can be fatal.
Card 467
What are six risk factors for acute gastritis?
Answer
1) Severe burn (Curling ulcer)
2) ^Similarly, shock
3) increased ICP (Cushing ulcer)
4) NSAID use (decreased PGE₂, which is protective of gastric mucosa)
5) Heavy alcohol consumption
6) Chemotherapy
Card 468
What are the two types of chronic gastritis?
Answer
Chronic autoimmune gastritis (type A) and chronic H. pylori gastritis (Type B)
Card 469
What antibodies are associated with chronic autoimmune gastritis?
What type of hypersensitivity is chronic autoimmune gastritis?
Answer
Type IV - this disease is mediated by T cells
*It's very important to understand that damage to the parietal cells is not a result of the anti-parietal cell or anti-IF antibodies seen on testing - these antibodies are merely a consequence of the damage inflicted on these cells
*Ignore FA: UWorld, Pathoma, and Goljan all agree it is type IV
Card 471
What is the most common cause of Vitamin B12 deficiency?
Answer
Chronic autoimmune gastritis leading to destruction of parietal cells which secrete intrinsic factor (pernicious anemia)
Card 472
What type of malignancy are patients with chronic autoimmune gastritis particularly at risk for?
Answer
Gastric adenocarcinoma
Card 473
What parts of the stomach does chronic autoimmune gastritis typically involve?
Answer
The fundus and the body (areas possessing highest number of parietal cells)
Card 474
What is the most common site of an H. pylori-induced gastric ulcer?
Answer
The lesser curvature of the antrum of the stomach
Card 475
What is the most common form of gastritis?
Answer
H. pylori induced gastritis
Card 476
What two malignancies are patients with chronic H. pylori gastritis at greatest risk for?
Answer
Gastric adenocarcinoma (intestinal type) and MALT lymphoma (of marginal cell origin)
*Remember from the blood disorders section that MALT lymphoma is a type of marginal zone lymphoma
Card 477
What is the most common cause of duodenal ulcers? What is rare but commonly tested cause of duodenal ulcers?
Answer
Most common: H. pylori.
Rare: Zollinger-Ellison syndrome
Zollinger-Ellison is a tumor of gastrin-secreting cells in the pancreas. Tumor-produced gastrin induces over-secretion of acid in the stomach, which overwhelms and degrades the duodenal mucosa as it passes through
Card 478
How are duodenal and gastric ulcers symptomatically different?
Answer
Gastric ulcers present with pain that is exacerbated by meals (eating stimulates acid secretion in the stomach)
Duodenal ulcers characteristically present with pain that improves with meals (eating stimulates bicarb secretion in the duodenum)
*Note: some texts also describe apparent weight gain with a duodenal ulcer, and weight loss with a gastric ulcer
Card 479
Besides H. pylori infection, what are two other possible causes of gastric ulcer?
Answer
Chronic NSAID use and bile reflux
*Might as well also plug the fact that a gastrin-secreting tumor will cause duodenal ulcers. As a general rule, the two causes of an ulcer are either disrupted mucosa or increased acid production
Card 480
What are the two types of gastric (adeno)carcinoma?
Answer
Intestinal and diffuse type
*These categorizations are known as the "Lauren Classification"
Card 481
What are the key differences between intestinal and diffuse gastric adenocarcinoma?
Answer
Intestinal: presents as a large, irregular ulcer with heaped up margins. It typically occurs in the same location as a gastric ulcer would - the lesser curvature of the antrum of the stomach.
Diffuse type: characterized by signet ring cells (these cells have a displaced nucleus, due to central mucus production), which diffusely infiltrate the intestinal wall. Desmoplasia commonly resulting in thickening of the stomach wall ("linitus plastica")
Card 482
What are three key risk factors for the development of intestinal type gastric adenocarcinoma?
Answer
1) Intestinal metaplasia (due to chronic H. pylori or autoimmune gastritis)
2) Nitrosamines in smoked foods (common cause of stomach cancer in Japan)
3) Blood type A
*Worth noting: "male sex" is not listed as a risk factor in pathoma, however, males are much more likely to get intestinal type gastric adenomcarcinoma, compared to females who are much more likely to develop diffuse type
Card 483
What malignancy can, on rare occassions, present with acanthosis nigricans or Leser-Trelat sign? What is a Leser-Trélat sign?
Answer
Gastric adenocarcinoma typically presents late with weight loss, abdominal pain, anemia, and early satiety. In rare instances, it can present with acanthosis nigricans or Leser-Trélat sign.
Leser-Trélat sign is a sudden onset of seborrheic keratoses (benign pigmented skin tumors) on the back (pictured)
Card 484
To which lymph node can gastric adenocarcinoma commonly spread?
Answer
The left supraclavicular node (also known as 'Virchow's node')
Card 485
Gastric carcinoma commonly metastasizes to which three locations? Which subtypes (intestinal/diffuse) are associated with each location?
Answer
Distant metastasis of gastric adenocarcinoma typically involves the liver. Typical of both subtypes.
Metastasis to the periumbilical region results in a characteristic Sister Mary Joseph nodule. This is only seen in intestinal type gastric carcinoma.
Bilateral metastasis to the ovaries is called a Krukenberg tumor. This is only seen in diffuse type gastric adenocarcinoma.
Card 486
Duodenal atresia is associated with what chromosomal abnormality?
Answer
Down syndrome
Card 487
What are three key clinical features of duodenal atresia?
Answer
Polyhydramnios (again, the developing fetus is not able to consume any amniotic fluid)
Bilious vomiting (contrast this to the nonbilious vomiting that one would see in a case of pyloric stenosis)
"double bubble" sign (distension of stomach, blind loop of duodenum)
*Important correlation: annular pancreas, which can constrict the duodenum as well, can also present in early childhood, with vaguely similar sounding symptoms. It is important to remember, however, that even though the duodenum is affected in annular pancreas, vomiting is usually non-bilious, since the pancreas often obstruct the duodenum at a higher level than the Ampulla of Vater.
Card 488
Meckel and Zenker diverticula: which is "true" and which is "false"? What is the difference between true and false diverticula?
Answer
1) Meckel diverticulum is a true diverticulum - all three layers of intestinal tract are involved in the outpouching.
2) Zenker diverticulum is a false diverticulum - inner layers of the tract protrude through the muscular layer
Card 489
Describe the "rule of 2" pertaining to Meckel Diverticulum:
Answer
Seen in 2% of the population
2 inches long and located in the small bowel within 2 feet of the ileocecal valve
Can present during first 2 years of life with bleeding, volvulus, intussception, or obstruction (mimicking appendicitis)
2 types of tissue: gastric and pancreatic
Card 490
What presents with a "coffee bean" sign on x-ray?
Answer
Volvulus (especially a sigmoid volvulus)
Twisting of bowel results in infarction
Card 491
What is the most common location for volvulus formation in an elderly patient? A young adult?
Answer
Elderly - sigmoid colon
Young adult - cecum
Card 492
What is intussusception? What are the common causes of intussception in children and adults?
Answer
Intussusception = peristalsis teloscopically pulls a non-smooth segment of bowel into the lumen. This most typically needs a "leading edge", or patch of rough endothelium, in order to occur.
children: lymphoid hyperplasia most common cause (due to rotavirus, more recently/controversially due to rotavirus vaccine)
adults: tumor
Card 493
Specifically, what are the classic antibodies found in Celiac disease (3)?
Answer
IgA / IgG against:
endomysium
tTG (tissue transglutaminase)
gliadin
*Important to note that a small proportion of patients with celiac also have a related IgA deficiency (significance of this association is unknown) - therefore it is very important to check both IgG and IgA antibodies
Card 494
What condition is dermatitis herpetiformis associated with? What causes it?
Answer
Celiac disease
It is caused by IgA deposition at the tips of dermal papillae. It tends to affect the knees and elbows
Card 495
What does the duodenal biopsy look like in a patient with Celiac disease (3 features)?
Answer
Flattening of the villi,
hyperplasia of crypts, and
increased intraepithelial lymphocytes.
The damage is MOSTLY in the duodenum; the jejunum and ilium are less involved.
Card 496
What should be on your differential diagnosis in a patient with refractory (unresponsive to dietary control) Celiac disease (2)?
Answer
Symptoms in refractory celiac may be related to:
Small bowel carcinoma
Enteropathy Associated T cell lymphoma (EATL)
*Important to note that EATL is somewhat unique in that it is a T cell lymphoma, one of the few (adult T cell lymphoma/leukemia and T ALL being the others)
Card 497
Which vitamin deficiencies can result from Tropical Sprue? Why?
Answer
Vitamin B₁₂ & folate (B9) - these vitamins absorbed in the jejunum and ilieum, which are primarily affected in tropical sprue
*Note that B₁₂ deficiency, while it could theoretically result from tropical sprue, is unlikely to, since it takes a long time for the body's endogenous stores of B₁₂ to be comsumed
Card 498
What organism causes Whipple disease?
Answer
Tropheryma whippelii
Card 499
What is the most common site of carcinoid tumor in the GI tract?
Answer
The small bowel (typically distal to the duodenum) - grows as submucosal polyp-like nodule
*It's probably mentioned elswhere but is important to note that carcinoid tumor is a low-grade malignancy. Of all neurendocrine tumors, it is the least malignant (compared to small cell carcinoma of the lung, the most malignant)