5/2 - UWorld

Question 1

What are the proteins involved in and function of gap junctions?

Answer 1

§ Proteins - Connexins

§ Function - Intercellular communication

Question 2

o What are the proteins involved in and function of tight junctions?

Answer 2

§ Proteins - claudins, occludin

§ Function - paracellular barrier

Question 3

o What are the proteins involved in and function of adherins junctions?

Answer 3

§ Proteins - cadherins

§ Function - cellular anchor

Question 4

o What are the proteins involved in and function of desmosomes?

Answer 4

§ Proteins - cadherins (e.g. desmoglein)

§ Function - cellular anchor

Question 5

What are the proteins involved in and function of hemidesmosomes?

Answer 5

§ Proteins - integrins

§ Function - cellular anchor

Question 6

Describe the geographic locations associated with histoplasmosis, blastomycosis, coccidiomycosis, and paracoccidiomycosis

Answer 6

Histo - Mississippi and Ohio river valleys (central US)

Blasto - Eastern and central US

Coccidio - Southwestern US

Para-coccidio - Latin America

Question 7

Describe the histologic appearance of histoplasmosis

Answer 7

Smaller than RBCs

Macrophage filled with ovoid cells

Question 8

Describe histologic appearance of blastomycosis

Answer 8

Round yeast with single broad based bud

Same size are RBCs

Question 9

Describe the histologic appearance of coccidiomycosis

Answer 9

Spherule filled with endospores

Much larger than RBCs

Question 10

Describe histology of para-coccidiomycosis

Answer 10

Budding yeast with “captain’s wheel formation”

Much larger than RBCs

Question 11

Describe the mechanism behind glucagon as a treatment for beta blocker toxicity

Answer 11

• Glucagon acts on G-protein coupled receptors, increasing intracellular cAMP, and thus increasing release of intracellular calcium during muscle contraction
• This increases heart rate and cardiac contractility

Question 12

Enzyme used to create ribose-5-phosphate in HMP shunt

Answer 12

Transketolase

Question 13

Causes and basic premise behind phenylketonurie (PKU)

Answer 13

Tyrosine deficiency

Due to:

o Deficiency in phenylalanine hydroxylase, or

o Deficiency in tetrahydrobiopterin cofactor (BH4)

Question 14

Basic premise behind maple syrup urine disease

Answer 14

THINK: I Love Vermont maple syrup from branched maple trees

§ Branches - blocked degradation of branched amino acids

§ I - Isoleucine

§ Love - leucine

§ Vermont - Valine

Question 15

Presentation of maple syrup urine disease

Answer 15

CNS defects, intellectual disability, and death

Question 16

Basic premise behind Alkaptonuria

Answer 16

Inability to degrade tyrosine due to defect of homogentisate oxidase

Question 17

Presentation of phenylketonuria

Answer 17

• Tyrosine becomes an essential amino acid
• Presentation:
  
  • Intellectual disability
  • Growth retardation
  • Seizures
  • Fair skin à inability to make melanin
  • Eczema

Question 18

Causes of homocysteinuria

Answer 18

o Cystathionine synthase deficiency

o Decreased affinity of cystathionine synthase for B6

o Methionine synthase deficiency

Question 19

Presentation of homocysteinuria

Answer 19

o Homocysteine in urine

o Marfanoid habitus

o Ocular changes (downward and inward lens subluxation – vs. Marfan which is upward)

o CV effects (thrombosis and atherosclerosis)

o Kyphosis

o Intellectual disability

Question 20

Cause of cystinuria

Answer 20

Defect in proximal convoluted tubule of the kidney in the COLA transporter (Cysteine, Ornithine, Lysine, Arginine)

Defect prevents reabsorption of COLA amino acids

Question 21

Presentation of cystinuria

Answer 21

Excess cysteine in urine can lead to hexagonal cysteine stones

Question 22

What is CREST syndrome?

Answer 22

· Calcinosis / anti-centromere antibody

· Raynoud

· Esophageal dysmotility

· Sclerodactyly (tightening of skin with loss of wrinkles)

· Telangiectasias

Question 23

Cause and presentation of Hyper-IgE Syndrome (aka Job)

Answer 23

o Deficiency in IFN-y lead to impaired neutrophil recruitment

o Presentation - FATED

§ F – coarse Facies

§ A – Abscesses

§ T – retained primary Teeth

§ E – increased IgE (all other immunoglobulins are normal)

§ D – dermatologic problems (eczema)

Question 24

Infliximab

Answer 24

• TNF-a inhibitor
  
  • Recall: TNF-a is an acute phase reactant produced by activated macrophages to mediate inflammation by accelerating neutrophil migration, and facilitate lymphocyte proliferation; TNF-a is responsible for fever, anorexia, corticotropin releasing hormone, septic shot, and cachexia
• Mechanism of action:
  
  • Is a monoclonal antibody to TNF-a
• Uses:
  
  • Used for autoimmune conditions due to anti-inflammatory effect
  • Rheumatoid arthritis, psoriasis, ankylosing spondylitis

Question 25

Etanercept

Answer 25

* TNF-a inhibitor * Recall: TNF-a is an acute phase reactant produced by activated macrophages to mediate inflammation by accelerating neutrophil migration, and facilitate lymphocyte proliferation; TNF-a is responsible for fever, anorexia, corticotropin releasing hormone, septic shot, and cachexia * Mechanism of action: * Mimics TNF-a receptor (aka it intercepts TNF-a before it can reach its target) * Uses: * Used for autoimmune conditions due to anti-inflammatory effect * Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriasis

Question 26

Cyclosporine

Answer 26

* Immunosuppressant * Blocks lymphocyte activation and proliferation * MOA: * Binds cyclophilin (protein within cytosol of T-cells) * Inhibits calcineurin (which stimulates IL-2) à prevention of IL-2 transcription * Uses: * Transplant rejection * Psoriasis * Rheumatoid arthritis * Toxicity * Nephrotoxicity

Question 27

Tacrolimus

Answer 27

* Immunosuppressant * Blocks lymphocyte activation and proliferation * MOA: * Binds FK506 binding protein * Inhibits calcineurin à prevention of IL-2 transcription * Uses: * Transplant rejection prophylaxis * Toxicity: * Nephrotoxicity

Question 28

Sirolumus

Answer 28

* (aka Rapamycin) * Immunosuppressant * Blocks lymphocyte activation and proliferation * MOA: * Binds FKBp12 à inhibition of mTOR * Prevents _response_ to IL-2

Question 29

Dacluzimab

Answer 29

* Immunosuppressant * Blocks lymphocyte activation and proliferation * MOA: * Binds CD25 (IL-2 receptor) à preventing response to IL-2

Question 30

Describe Wiskott Aldrich syndrome

Answer 30

o X-linked recessive immunodeficiency - due to T cells unable to reorganize actin skeleton o WATER - Wiskott Aldrich, Thrombocytopenia, Eczema (especially truncal), Recurrent infections

Question 31

Antibody associated with mixed connective tissue disease

Answer 31

Anti-U1 RNP (ribonucleoprotein)

Question 32

Antibody associated with polymositis and dermatomyositis

Answer 32

Anti-Jo-1

Question 33

Defective enzyme and presentation of fructose intolerance

Answer 33

§ Defect in aldolase B (Fructose-1-phosphate -\> Glyceraldehyde or DHP) § F1P will accumulate, decreasing the available phosphate, and inhibiting glycogenolysis and gluconeogenesis § Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting · THINK: Boyfriend giving present of heels (Aldo shoes) + chocolate covered strawberries (fructose)

Question 34

What are the classic immunologic cells found in sarcoidosis

Answer 34

Elevated CD4+/CD8+ T-cell ration in bronchoalveolar lavage