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Flashcards in UWorld 2 Deck (62):
1

Obstructive sleep apnea

Pathophys
1) Relaxation of pharyngeal muscles leads to closure of airway
2) Loud snoring with periods of apnea

Symptoms
1) Daytime somnolence
2) Non-restorative sleep with frequent awakenings
3) Morning HAs
4) Affective and cognitive symptoms

Sequelae
1) Systemic HTN
2) Pulm HTN and right HF

Obesity is most important risk factor.

2

EPO in OSA

Short periods of hyopnea and apnea reduce blood oxygen levels. The kidneys respond to hypoxemia by increasing EPO.

EPO stimulates bone marrow to differentiate more RBCs. Therefore, it is quite common for patients with OSA to have elevated hematocrit levels (polycythemia)

Polycythemia and erythrocytosis are used interchangeably. Polycythemia is lab finding of elevated RBC count and hematocrit. Relative polycythemia is usually due to reduced blood volume (look for diarrhea or vomiting or blood loss), whereas absolute polycythemia (erythrocytosis) is due to increased RBC mass and can be primary (PV) or secondary (due to chronic hypoxia or EPO-producing tumors)

3

Elderly patient with evidence of osteolytic lesions on XR

always suspect MM. Screening tests of choice are spep, upep, and free light chain analysis. Dx is confirmed by bone marrow bx.

4

Why are post-splenectomy patients at higher risk of sepsis from encapsulated organisms?

Impaired antibody-mediated opsonization in phagocytosis.

Normally, blood borne antigens enter spleen via splenic artery and are phagocytosed by dendritic cells in white pulp.

these dendritic cells then present antigens in association with MHC II to Th cells, activating them. Activated Th cells migrate to marginal zone of spleen where they come in contact with B cells in primary follicles.

B cell activation causes secondary follicles and plasma cell-rich germinal centers to form

Antibodies produced by germinal center plasma cells enter systemic circulation, bind their specific antigen, and facilitate phagocytosis of pathogenic organisms by opsonization.

5

What condition features a defect in intracellular killing?

Chronic granulomatous disease - X recessive (or auto recessive) defect in NADPH oxidase

6

Heterophile antibody test and EBV mono

IM manifests as extreme fatigue, malaise, sore throat, fever and a generalized maculopapular rash.

Posterior cervical LAD and palatal petechiae can be present.

Splenomegaly is also common.

Heterophile antibody test is very sensitive and specific but may be negative early on (maybe 5 days). Repeating test is helpful.

7

Rivaroxaban

Direct Factor 10a inhibitor with rapid onset of action. Can be used as single agent in tx of acute DVT or PE. Does NOT require lab monitoring or overlap with heparin.

It does have drug interactions and carries higher risk of irreversible bleeding (no antidotes in event of major hemorrhage).

Patients may be interested in rivaroxaban if they do not want daily injections (heparin) or if they have difficulty with dietary restrictions or frequent INR checks (warfarin)

Also good option for patients with recurrent or refractory DVT

Look for subtherapeutic INR in warfarin patient

8

Rivaroxaban vs Warfarin

Rivaroxaban
1) Direct factor 10a inhib
2) 2-4h for effect
3) Single agent
4) No need for monitoring
5) No antidote

Warfarin
1) Vit K antagonist
2) 5-7d for effect
3) Overlap with heparin for about 5d
4) Monitor PT/INR
5) Antidote is FFP, Vit K

9

2 important diagnostic clues for Waldenstrom's macroglobulinemia

1) IgM spike (MM is usually IgG or IgA)
2) Hyperviscosity

10

Contraindication to anticoagulation

Complications from anticoagulation, significant active bleeding, recent surgery, acute hemorrhagic stroke

11

Patient with first episode of VTE and no clear provoking factors (recent procedure, immobilization)

Refer for age appropriate cancer screening.

If there is concern for occult malignancy (due to suggestive symptoms like weight loss or pain), extensive cancer screening (CT CAP) can be considered

Extensive testing for underlying inherited cause (def of protein C, protein S or antithrombin 3) is usually only done when patient's history is suggestive (less than 45 years old, multiple or unusual sites of thrombosis, family history of VTE)

12

Recommendations for lung cancer screening

Recommended test - low dose CT

Recommended interval - yearly

Age for screening - 55-80

Eligibility for screening based on smoking history
1) Patient has at least 30 pack year smoking history AND
2) Patient is a current smoker or quit within last 15 years

Termination of screening
1) Age over 80 OR
2) Patient successfully quit smoking for at least 15 years OR
3) Patient has other medical problems that significantly limit life expectancy or ability/willingness to undergo lung cancer surgery

13

principles to use of pain meds in patients with terminal cancer

1) Try non-narcotic measures first unless you are sure (using clinical judgment) that the patient is in severe pain
2) Do not be afraid to give narcotics (half of cancer patients die in significant pain)
3) Prescribe adequate amounts of meds

Start with short-acting morphine. Once dose is established switch to long acting narcotic with the short acting morphine for break through pain.

14

Fe deficiency anemia vs alpha thalassemia minor vs Beta thalassemia minor (7 parameters)

MCV
1) Fe def - low
2) Alpha minor - low
3) Beta minor - low

RDW
1) Fe def - up
2) A minor - normal
3) B minor - normal

RBCs
1) Fe def - low
2) A minor - normal
3) B minor - normal

Peripheral Smear
1) Fe def - microcytosis, hypochromia
2) A minor - Target cells
3) B minor - Target cells

Serum iron studies
1) Fe def - low iron, low ferritin, high TIBC
2) A minor - Normal/high iron and ferritin (RBC turnover)
3) B minor - same as A minor

Response to iron supplementation
1) Fe def - increased Hgb
2) A minor - No improvement
3) B minor - No improvement

Hgb electrophoresis
1) Fe def - normal
2) Alpha minor - Normal
3) B minor - Increased HgbA2

15

Sign of B thalassemia trait (compared to Fe def)

Microcytosis out of proportion to degree of anemia (often Hgb is above 10) and a disproportionately high RBC count

Fe def usually has a low RBC count, and microcytosis isn't usually seen until Hgb is less than 10.

16

Regional preferences of the thalassemias

Alpha - Southeast Asia
Beta - Mediterranean

17

Alpha thalassemia silent carrier

aa/a-

Normal Hb electrophoresis. Asymptomatic

18

Alpha thalassemia trait

aa/-- OR a-/a-

Normal Hb electrophoresis. Mild symptoms.

19

Hb H disease

a-/--

Electrophoresis shows 5-30% HbH in adults. Patient will have chronic hemolysis. This is a type of alpha thalassemia

20

Alpha thalassemia major

--/--

Electrophoresis shows:
1) Hb Barts, Hb Portland, and HbH present
2) Absent Hb A, Hb F, and Hb A2

Fatal in utero (fetal hydrops)

21

Beta thalassemia trait

B/B0

Increased HbA2 on electrophoresis. Mild symptoms.

22

Beta thalassemia intermediate

B+/B+ and others

Increased HbF on electrophoresis. Moderate symptoms

23

Beta thalassemia major

B0/B0

Absent HbA, only HbA2 and HbF on electrophoresis. Severe symptoms.

24

When you start EPO in an ACD patient (maybe with ESRD), what should you also give?

Ensure patient has adequate iron supplementation to handle the surge in RBC production.

Evaluate iron stores BEFORE starting EPO. Tx of choice for iron deficiency in a dialysis patient is IV iron dextran

25

When is folic acid supplementation indicated? (other than pregnancy)

Folate deficiency and hereditary spherocytosis

26

Heme manifestations (2 major ones) from type 2 HIT

1) Thrombocytopenia - reticuloendothelial system (largely the spleen) removes antibody-coated platelets, causing a mild to moderate thrombocytopenia (rarely less than 20k)

2) Arterial and venous thrombus - HIT antibodies activate platelets, resulting in aggregation and the release of procoagulant factors. Risk of thrombus is as high as 50% in untreated HIT

27

How does heparin work?

It binds antithrombin, which inactivates factor Xa. This prolongs PTT

28

How soon does type 2 HIT occur?

Usually 5-10 days, but it can be sooner (sometimes even less than 1 day) in patients previously exposed. Keep in mind that a patient with ESRD on dialysis is most likely getting heparin during dialysis sessions.

29

Drugs that cause folic acid deficiency

1) Phenytoin, Primidone, Phenobarbital - impaired absorption of folic acid in the small intestine.

2) Trimethoprim - it inhibits dihydrofolate reductase and in high doses can cause megaloblastic pancytopenia.

3) Methotrexate - Also inhibits DHF reductase. Folinic acid (leucovorin) is indicated to reverse the chemotherapeutic anti-folate effect of MTX

Give folic acid with these drugs.

30

Febrile nonhemolytic transfusion rxn

Most common rxn.

1) Fever and chills
2) Within 1-6h of transfusion
3) Caused by cytokine accumulation during blood storage

31

Acute hemolytic transfusion rxn

1) Fever, flank pain, hemoglobinuria, renal failure and DIC

2) Within 1h of transfusion

3) Positive direct Coombs test, pink plasma (plasma free Hb above 25)

4) Caused by ABO incompatibility

32

Which transfusion reaction is caused by anamnestic antibody response?

Delayed hemolytic

1) Mild fever and hemolytic anemia

2) Within 2-10d after transfusion

3) Positive direct Coombs, positive new antibody screen

33

Which transfusion reaction is caused by recipient anti-IgA antibodies?

Anaphylactic

1) Rapid onset of shock, angioedema/urticaria and respiratory distress

2) Within a few seconds to minutes of transfusion

34

Which transfusion reaction is caused by recipient IgE antibodies and mast cell activation?

Urticarial/Allergic

1) urticaria, flushing, angioedema and pruritus

2) Within 2-3h of transfusion

35

Which transfusion reaction is caused by donor anti-leukocyte antibodies?

Transfusion-related acute lung injury

1) Respiratory distress and signs of noncardiogenic pulmonary edema

2) Within 6h of transfusion

36

Intravascular vs extravascular hemolysis causes

Intravascular - due to significant RBC structural damage resulting in RBC destruction within the intravascular space. Hemoglobin released from hemolyzed RBCs binds to haptoglobin and the Hb-Hapto complex is cleared by liver. Leads to marked reduction in serum haptoglobin and elevated indirect bili (from heme breakdown) and raised LDH (released from RBCs)
1) Microangiopathic hemolytic anemia (DIC)
2) Transfusion reactions
3) Infections (clostridial sepsis)
4) PNH
5) IV Rho(D) immune globulin infusion

Extravascular - RBCs predominantly destroyed by phagocytes in the reticuloendothelial system (LNs, spleen). Less Hb release than in intravascular. Labs show normal or slightly low haptoglobin. Slightly elevated LDH. Elevated indirect bili.
1) Intrinsic RBC enzyme deficiencies (G6PD)
2) Hemoglobinopathies (sickle cell, thalassemia)
3) Membrane defects (hereditary spherocytosis)
4) Hypersplenism, IVIG infusion
5)*** Warm or cold agglutinin autoimmune hemolytic anemia (most cases)
6) Infections (Bartonella, malaria)

37

Warm agglutinin AHIA

Etiology
1) Drugs (penicillin)
2) Viral infections
3) AI (SLE)
4) Immunodeficiency states
5) Lymphoproliferative (CLL)

Clinical
1) ASx to life threatening anemia
2) Direct Coombs positive with anti-IgG, anti-C3, or both

Tx
1) Corticosteroids
2) Splenectomy for refractory disease

Complications
1) VTE
2) Lymphoproliferative disorders

38

Cold agglutinin AHIA

Etiology
1) Infections (Myco pneumonia and infectious mono)
2) Lymphoproliferative diseases

Clinical
1) Symptoms of anemia
2) Livedo reticularis and acral cyanosis with cold exposure that disappear with warming
3) Direct Coombs positive with anti-C3 or anti-IgM, but usually NOT IgG

Tx
1) Avoidance of cold temps
2) Rituximab with or without fludarabine

Complications
1) Ischemia and peripheral gangrene
2) Lymphoproliferative disorders

39

Migratory Superficial Thrombophlebitis

Trousseau's Syndrome

A hypercoagulable disorder that usually presents wit unexplained superficial venous thrombosis at unusual sites (arm, chest area). The syndrome is usually diagnosed prior to (sometimes months to years before) or at the same time as an occult visceral malignancy

Usually associated with cancer involving the pancreas (most common), lung, prostate, stomach and colon and acute leukemias.

Factors associated with higher risk of pancreatic cancer include increasing age and smoking.

Tumor likely releases mucins that react with platelets to form platelet-rich microthrombi.

Refer these patients for CT of abdomen to look for occult tumor.

40

Can macrovascular hemolysis cause microcytic anemia?

Sure. ESP in patients with artificial heart valves or severely calcified aortic valves.

41

Sickle Cell Disease and Folate deficiency

SCD can cause Folate deficiency due to high red blood cell turnover and increased consumption of folate in the bone marrow

Daily folic acid recommended for all sickle cell patients.

Keep in mind that hydroxyurea can cause macrocytosis (along with TMP, phenytoin and MTX)

42

Polycythemia Vera

PV is a clonal myeloproliferative disorder

Manifestations
1) Increased blood viscosity - HTN, Erythromelalgia (burning cyanosis in hands/feet), transient visual disturbances
2) Increased RBC turnover (gouty arthritis)
3) Aquagenic pruritus
4) Bleeding

Exam
1) Facial plethora (ruddy cyanosis)
2) Splenomegaly

Lab
1) Elevated hemoglobin
2) Leukocytosis and thrombocytosis
3) Low EPO level (unlike most causes of secondary polycythemia)
4) JAK2 mutation

Complications
1) Thrombosis
2) Myelofibrosis and acute leukemia

Tx
1) Phlebotomy**
2) Hydroxyurea (if increased risk of thrombus)

43

Immune thrombocytopenia

AKA ITP. It's an autoimmune disorder resulting in increased platelet destruction and inhibition of megakaryocyte platelet production due to IgG autoantibodies against the platelet membrane glycoproteins.

Presentation
1) Antecedent viral infection
2) ASx petechiae and ecchymosis most common
3) Mucocutaneous bleeding (epistaxis, hematuria, GI bleed)
4) No other physical exam findings (HSM not there)

Lab
1) isolated thrombocytopenia less than 100k
2) Peripheral smear with megakaryocytes and no other abnormalities

Tx- Kids
1) Skin manifestations only - observe
2) Bleeding - IVIG OR glucocorticoids

Tx-Adults
1) Platelets at least 30k without bleeding - observe
2) Platelets less than 30k OR bleeding - IVIG or glucocorticoids

Other than history, physical exam, CBC, and exam of the blood smear, the only other tests recommended in patients with presumptive ITP include HIV and hep C testing (if risk factors are present). Treatment of underlying disease may alter course of ITP

44

Bernard Soulier

Auto recessive due to absent glycoprotein 2b-IX-V, which acts as a receptor for vWF.

Patients usually have mild thrombocytopenia, circulating giant platelets, severe platelet dysfunction, and bleeding out of proportion to the degree of thrombocytopenia

45

von Willebrand Disease

Most common inherited bleeding disorder due to deficiency of vWF.

Patients with this disease have prolonged bleeding time and activated partial thromboplastin time. Platelet counts usually normal.

46

Hereditary spherocytosis

Epi
1) Auto dominant (75%)
2) Northern european

Clinical presentation
1) Hemolytic anemia
2) Jaundice
3) Splenomegaly

Lab
1) High MCHC (due to membrane loss and RBC dehydration)
2) Spherocytes on smear
3) Negative coombs
4) Increased osmotic fragility on acidified glycerol lysis test
5) Abnormal eosin-5-maleimide binding test

Tx
1) Folic acid supplementation
2) Blood transfusions
3) Splenectomy

Complications
1) Pigment gallstones
2) Aplastic crisis from parvoB19 infection

47

B12 def and DNA synthesis

B12 is important in formation of thymidylate and purine molecules for DNA synthesis

B12 therefore causes ineffective erythropoiesis due to delayed nuclear maturation, resulting in decreased transition to mature RBC forms and high numbers of immature megaloblasts in bone marrow.

Increased intramedullary hemolysis of these megaloblasts releases heme, causing indirect hyperbilirubinemiam which may manifest as jaundice.

May see high LDH. Total RBC count and reticulocyte count will be low.

Patients may also develop thrombocytopenia and leukopenia with hypersegmented PMNcells

48

Clinical features of androgen abuse

Types of androgens
1) Exogenous (testosterone replacement therapy)
2) Synthetic (stanozolol, nandrolone)
3) Androgen precursors (DHEA)

Repro
1) Men - lower testicular function and sperm production, gynecomastia
2) Women - Acne, hirsutism, voice deepening, menstrual irregularities

Cardio - LVH, possible low HDL and high LDL

Psych - aggressive behavior (men), mood disturbances

Heme***- Polycythemia, possible hypercoagulability

49

Clopidogrel mech

Antiplatelet. Blocks adenosine diphosphate receptors on surgace of platelets.

Used in treatment of arterial thrombosis (MI, stroke) but not in VTE

50

Homocysteine metabolism

Homocysteine is a highly reactive amino acid. Increased levels predispose to VTE as well as atherosclerosis, prob due to combo of direct vascular damage, activation of clotting mechanisms, and inhibition of antithrombotic pathways. DVT tx in setting of elevated homocysteine levels should include lowering of homocysteine

Homocysteine can be metabolized to cysteine or methylated to form methionine. If either of these paths are interrupted by an enzyme or cofactor deficiency, elevated homocysteine levels result.

Homocysteine to cysteine is catalyzed by cystathionine B-synthase using the cofactor pyridoxine** (B6).

Homocysteine to methionine is catalyzed by methylenetetrahydrofolate reductase (MTHFR) and methionine synthase, with folate and B12 (cobalamin) as essential cofactors.

Tx - Independent of the underlying cause, homocysteine levels can be normalized by giving B6 and Folate. B12 should be added if B12 deficiency is documented. Unclear if this reverses the hypercoagulability though (def normalizes levels tho)

51

Patient with hemolytic anemia and thrombocytopenia - suspect what?

TTP

52

Sideroblastic anemia

Can be acquired. From defective heme synthesis, most commonly due to pyridoxine-dependent impairment in early steps of protoporphyrin synthesis. Isoniazid is a well known pyridoxine antagonist that can be responsible.

Acquired sideroblastic anemia frequently presents as microcytic hypochromic anemia simulating iron deficiency anemia. Usually 2 groups of RBC can be demonstrated on microscopy. Hypochromic and normochromic (dimorphic RBC population).

Besides that, iron studies typically show increased serum iron concentration and decreased TIBC.

BM bx is confirmatory but not needed.

In patients with an identifiable cause of B6 deficiency (alcoholism, drugs), the administration of pyridoxine can easily correct the problem

53

Indications for Irradiated RBC tx

1) Bone marrow transplant recipients

2) Acquired or congenital cellular immunodeficiency

3) Blood components donated by first or second degree relatives

54

Indications for leukoreduced RBC tx

1) Chronically transfused patients

2) CMV seronegative at risk patients (AIDS, transplant patients)

3) Potential transplant recipients

4) Previous febrile nonhemolytic transfusion rxn**

55

Indications for Washed RBC tx

1) IgA deficiency

2) Complement-dependent autoimmune hemolytic anemia

3) Continued allergic reactions (hives) with red cell transfusion despite antihistamine treatment

56

CLL

Most common leukemia in USA. Median age 70. Often ASx patient but can present with extreme fatigue, B symptoms, infection or weight loss.

Clinical
1) LAD (cervical, supraclavicular, axillary)
2) HSM
3) Mild thrombocytopenia and anemia
4) Often ASx

Diagnostic
1) Severe lymphocytosis and smudge cells
2) Flow cytometry*** (shows clonality of mature B cells. Diagnostic)
3) LNs and bone marrow bx not generally needed

Prognostic
1) Median survival 10y
2) Worse prognosis with multiple chain LAD, HSN, anemia and thrombocytopenia

Complications
1) Infection
2) AIHA
3) Secondary malignancies (Richter transformation)

57

Hyposthenuria

Impairment in kidney's ability to concentrate urine.

Found in patients with Sickle Cell Disease, but is also common, though less severe in patients with sickle cell trait.

Look for black person with history of fatal blood disease.

Thought to result from RBC sickling in vasa rectae of inner medulla, which impairs countercurrent exchange and free water reabsorption.

58

Pica

Appetite for items other than food, such as paper products, clay or dirt. It is a behavioral symptom that occasionally develops in iron deficiency anemia.

Pagophagia is pica for ice and is quite specific for iron deficiency. It may be present before anemia develops and responds rapidly to iron supplements.

Pica may also be manifestation of psych disease - these patients may eat very odd items, including light bulbs or hair.

59

Modified Wells Score

For pretest probability of DVT. 1 or less makes DVT unlikely. 2 or more makes DVT likely. Give 1 point for each (except number 10):

1) Previously documented DVT
2) Active cancer
3) Recent immobilization of the legs
4) Recently bedridden more than 3d
5) Localized tenderness along vein distribution
6) Swollen leg
7) Calf swelling more than 3cm compared to other leg
8) Pitting edema
9) Collateral superficial nonvaricose veins
10) Alternate diagnosis more likely (you lose 2 points for this)

60

Lead poisoning in adults

Risk factors - occupational exposure (lead paint, batteries, ammunition, construction)

Clinical features
1) GI (abdominal pain, constipation, anorexia)
2) Neuro (cognitive deficits, peripheral neuropathy)
3) Heme (anemia)

Lab
1) Anemia
2) Elevated venous lead level
3) Elevated serum zinc protoporphyrin level
4) Basophilic stippling on smear

Lead is readily absorbed via respiratory (in adults) or GI (kids) tracts. It is 99% bound to RBCs and disrupts Hb synthesis at high levels (at level above 80) to cause microcytic anemia.

Dx is made by blood levels, CBC with smear and XR fluorescence to measure bone lead concentration

Tx - chelation therapy

61

Cancer related anorexia/cachexia syndrome (CACS)

Hypercatabolic state associated with weight loss, anorexia, and an excessive reduction in skeletal muscle.

Weight loss is multifactorial and thought to be a result of systemic inflammation in addition to caloric reduction. Nutritional counseling and supplementation with enteral or parenteral feeding do little to reverse CACS

Pharm interventions with progesterone analogues (megestrol acetate) or corticosteroids is effective at increasing appetite, causing weight gain, and improving well-being. In patients with longer life expectancies, progesterone analogues are preferred due to fewer side effects.

Canabinoids are mildly better than placebo for CACS but progesterone is far superior. For HIV cachexia, Canabinoids are useful.

62

Most common cause of iron deficiency anemia in adult male or post menopausal woman?

GI blood loss. Test for occult blood in stool.