Diseases

Question 1

4 Clinical Signs of Anemia

Answer 1

1. Weakness, fatigue, dyspnea
2. Pale conjunctiva and skin
3. Headache and lightheadedness
4. Angina, especially with pre-existing coronary disease

Question 2

4 Causes of microcytic anemia

Answer 2

1. Iron deficiency
2. Anemia of chronic disease (Fe locked in macrophages, can’t be used)
3. Sideroblastic anemia (decreased protoporphyrin)
4. Thalassemia (decreased production of globin chains)

Question 3

4 Stages of Iron deficiency

Answer 3

1. Storage iron depleted (dec. ferritin, inc. TIBC)
2. Serum iron depleted (dec. serum iron, dec % sat)
3. Normoctic anemia - BM makes fewer, normal-sized RBC
4. Microcytic, hypochromatic anemia - BM makes smaller and fewer RBC’s.

Question 4

3 Clnical features of iron deficiency

Answer 4

1. Anemia
2. Koilonychia
3. pica

Question 5

Explain FEP levels in Iron deficiency anemia

Answer 5

FEP = Free erythrocyte protoporphyrin
Dec Fe levels leads to unbound protoporphyrin levels in the blood. (protoporphyrin levels are normal).
Therefore FEP is increased.

Question 6

Anemia of Chronic disease, mechanism

Answer 6

Hepcidin sequesters iron in storaged sites by limiting iron transfer from macrophages to erythroid precursors and suppressing EPO production; aims ot prevent bacteria from accessing iron, which is necessary for bacterial survival.

Question 7

Sideroblastic Anemia, mechanism

Answer 7

Anemia due to defective protoporphyrin synthesis. Iron enters mitochondria, but without Fe, cannot leave, leading to ringed sideroblasts around the nucleus in erythroid precursers.

Question 8

Congenital defect leading to sideroblastic anemia

Answer 8

Defect in ALAS, the rate limiting enzyme that converts succinyl CoA to ALA with B6 cofactor

Question 9

3 Acquired causes of sideroblastic anemia

Answer 9

1. Alcoholism (mitochondrial poison)
2. Lead poisoning (inihibits ALAD (ALA–>prophorbilinogen) and Ferroketylase in mitochondria (final step to make heme))
3. Vit. B6 deficiency - required cofactor for ALAS, most commonly seen as side effect of isoniazid treatment for Tb

Question 10

2 MCC of megaloblastic anemia

Answer 10

1. B12 deficiency

2. Folate deficiency

Question 11

a-Thalassemia

Answer 11

Gene deletion, normally 4 alpha genes on chromosome 16.
1 deletion - asymptomatic
2 deletions - mild anemia and increased RBC ct
3 deletions - severe anemia, B chains form HBH tetromers
4 deletions - lethal in utero (hydrops fetalis) gamma chains form tetramers (Hb Barts) that damage RBCs

Question 12

B-Thalassemia minor

Answer 12

(B/B+) - diminished B production (B+)

• mild form of disease, increased RBC count
• Microcytic, hypochromatic RBCs and target cells (due to dec Hb, inc room in RBC membrane for blabbing)
• isolated increase in HbA2 (A2Delta2)

Question 13

B-Thalassemia Major

Answer 13

B0/B0
No B-chain production: severe anemia
- Unpaired alpha chains ppt and damage RBC membranes resulting in ineffective erythropoiesis and extravascular hemolysis (removal of circulating RBC by spleen)
- Massive erythroid hyperpasia ==> crewcut skull, chipmunk facies, extramedulalary hematopoiesis, hepatosplenomegaly, risk of aplastic crisis with parvovirus B19 (can’t risk shutdown of RBC production)

Question 14

3 Acute signs of Acute leukemia

Answer 14

1. Anemia (fatigue, pallor, dyspnea)
2. Thrombocytopenia (bleeding, bruising)
3. neutropenia (infection)

Question 15

Organ Dysfunction in Multiple Myeloma

Answer 15

CRAB:
Calcium elevation in blood
Renal insufficiency
Anemia
Bone lesions (lytic) or osteoporosis

Question 16

DIagnosis of MM, 3 criteria required

Answer 16

1. Monoclonal plasma cells in BM >10% and/or biopsy
2. Monoclonal protein in serum and/or urine
3. Myeloma-related organ dysfunction (CRAB)

Question 17

Dyskeratosis Congenita

Answer 17

Dyskeratosis Congenita = DKC
X-linked, mutation in DKC1, a member of the telomerase complex.
Associated Symptoms:
By age 5, skeletal abnormalities, skin changes (cafe au last), and bone marrow failure
Management = stem cell transplantation has had inconsistent results

Question 18

Fanconi Anemia

Answer 18

Autosomal recessive
Fanconi Anemia Complex is involved in a DNA repair pathway. If this pathway fails, normally cells are targetted for apoptosis.
Fanconi mutation –> no ubiquitination –> cancer

• associated with cafe au lait, no thumb (skeletal abnormalities), predisposition to anemias, broad face

Question 19

Schwachman-Diamond Syndrome

3 symptoms

Answer 19

Inherited disorder

1. exocrine pancreatic insufficiency (fat malabsorption)
2. Bone marrow failure
3. skeletal abnormalities

Question 20

Schwachman-Diamond Syndrome

Pathogenesis

Answer 20

SBDS mutation on chromosome 7

Induces accelerated apoptosis via FAS pathway

Question 21

Pure Red Cell Aplasia

Answer 21

Pure Red Cell Aplasia (PRCA)

• Aplasia selective to erythroid cell line, MC in females, Immune mechanisms
  1. autoimmune cytotoxic t cells
  2. Ab against erythroid precursors
  3. Acquired associations: Thymoma, Parvovirus B19

Question 22

Diamond Blackfan Anemia

Answer 22

presents first 3 months of life, mutation in ribosomal subunit 19, leads to short stature, triphalngeal (long) thumbs, cardiac septal defects, cleft lip/palate, webbed neck.

Pt has no RBC precursors, WBC/platelets are normal

“extra finger to put a diamond on. i’m a fan”

Question 23

Parvo B19 associated symtom

Answer 23

slapped cheek syndrome (fifth disease), aquired red cell aplaisa in immunocompromised host

Question 24

Paroxysmal nocturnal hemoglobinuria

mechanism and triad of clinical features

Answer 24

No GPI anchor.
CD55 and CD59 cannot bind RBCs.
Complement wins.

Clinical features:

1. intravascular hemolysis (abdominal pain, hemoglobinuria)
2. Thrombosis (cerebra, budd-chiari)
3. Bone Marrow Failure (precedes PNH, aplastic anemia)

Question 25

8 Bradford HIll Guidelines for causation

Answer 25

1. Temporality 2. Strength of association 3. Dose Response 4. Reversibility (cessation of exposure) 5. Consistensy with other knowledge 6. Biological Plausibility 7. Specificity of association 8. Analogy 9. coherence

Question 26

Bloom Syndrome

Answer 26

Mutation in BLM, which has DNA helicase activity and normally maintiains genomic instability. (predisposition to cancer w BLM mutation) acute leukema, lymphoma, GI adenocarcinoma

Question 27

Xeroderma pigmentosum

Answer 27

mutations in XP genes affect GG-NER and TC-NER ... severe UV sensitivity, skin cancer

Question 28

Ataxia Telangiectasia

Answer 28

ATM genes encodes protein kinase ATM, regulator of cellular response to double strand breaks. - predispose kids to lymphocytic leukemia, lymphoma

Question 29

Wilms Tumor/ Nephroblastoma

Answer 29

WT1 encodes TF critical to normal renal and gonadal development. WT1 mutation leads to asymptomatic abdominal mass.

Question 30

Fanconi's anemia

Answer 30

Mutation is in nuclear complex proteins involved in DNA damage response mechanisms. Leads to bone marrow failure, short stature, Cafe au lait spots

Question 31

Lynch Syndrome (HNPCC)

Answer 31

(Autosomal dominant) mutations in genes in volved in DNA MISMATCH REPAIR, loss of "proof reading" capacity Leads to familial carcinoma of the colon

Question 32

B and T cell lymphoid neoplasms (associated mutations)

Answer 32

``` mutations in RAG1 and RAG2 (VDJ recombination), and Antigen induced cytosine deaminase mutations (AID), involved in class switching recombination. Presents as severe UV sensitivity, skin cancer ```

Question 33

Chronic Granulomatous Disease | Path, features, screening test

Answer 33

Mutations in the NADPH oxidase system X-linked recessive 3 months - 2 years old, failure to thrive. Recurrent fevers. Pneumonia caused by a fungus likely to be due to CGD. Cat + Bacteria cause infection in CGD. Nitroblue tetrazolium (NBT) test screens by reacting with ROS, indicates if NADPH is deficient. (negative test: doesn't turn blue because no formation of ROS: CGD) Treat w prophylaxis

Question 34

Glutathione Synthetase deficiency

Answer 34

Glutathione = reducing agent in liver, deficient in a rare autosomal recessive disorder Hemolytic anemia with splenomegaly in moderate deficiency. Sever deficiency includes infections and neurologic defects.

Question 35

Myeloperoxidase Deficiency

Answer 35

Most are benign and asymptomatic Can't make bleach: ROS takes longer to kill bacteria without hte bleach. Susceptable to fungi (i.e. candida

Question 36

Pelger-Huet Anomoly

Answer 36

No clinical phenotype Congenital autosomal dominant disorder in which granulocyte nuclei do not segment normally. homozygotes: round nuclei Heterozygotes: bilobed nuglei ("pince nez cells") - cell function is normal

Question 37

Leukocyte Adhesion Deficiency

Answer 37

LAD1 - failure to express CD18 such that leukocytes are unable to undergo normal adhesion and chemotaxis. LAD III: mutation in Kindlin Result: recurrent bacterial infections, granulocytosis Patients usually die of infection wihin 2 years of birth Pus looks sterile! no neutrophils, but bacteria is present!

Question 38

Job's syndrome (Hyper IgE syndrome) | - triad

Answer 38

1. Eosinophilia, 2. eczema, 3. Recurrent sinopulmonary and cutaneous infections Broad nose, deep set eyes Etiology: Mutation in STAT3 Elevated IgE, dec. production of interferon gamma/Th17, decreased neutrophil chemotaxis.

Question 39

Chediak Higashi Syndrome

Answer 39

Problem with granule formation due to failed intracellular protein transport Big, disfunctional granules Clinically: albinism, recurrent infections (mucocutaneous and sinopulmonary), bleeding due to platelet aggregation defect Bad bad bad prognosis without allogeneic hematopoietic transplant

Question 40

X-linked Agammaglobinemia (Bruton Syndrome)

Answer 40

Mutation in Brutons tyrosine kinase (Btk) on X chromosome Btk usual activates MAP Kinase Leads to block in B cell development at preB to immature B cell stage. No making of antibodies bc no plasma cells High risk of encapsulated bacterial infections and pts may NOT receive live virus vaccines

Question 41

Common Variable Immunodeficiency

Answer 41

hypogammaglobinemia, variably low levels of IgG, IgA, and/or IgM - infections respond to Abx but recur upon discontinuation of meds

Question 42

Selective IgA deficiency

Answer 42

SIGAD - mild genetic immunodeficiency - risk of anaphylactic response to plasma-containing products (careful when treating these pts) - pts launch immune response to IgA

Question 43

Selective Deficiency of IgG subtypes

Answer 43

They exist. Treat them.