Things to review!!

Question 1

Treatment of psoriasis

Answer 1

topical vitamin D analogs (Calcipotiene, calcitriol, and tacalcitol) bind to and activate the vitamin D receptor, a nuclear transcription factor that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte differentiation

Question 2

Xeroderma Pigmentosum

Answer 2

autosomal recessive. Extreme sensitivity to light.

o Results from a defective excision repair mechanism for UV-damaged DNA, which leads to thymine dimers (when the thymidine nucleotides form hydrogen bonds with each other rather than with their complementary bases on the opposite DNA strand).

o Caused by a mutation in endonuclease: normally repairs thymine dimers

Question 3

Stem cell locations (in skin, bowel, and bone marrow and lung):

Answer 3

skin – basal layer
bowel – mucosal crypts
bone marrow – hematopoietic stem cells
lung – type 2 pneumocytes

Question 4

McCune Albright Syndrome

Answer 4

due to mutation affecting G protein signaling which causes constitutive activation of the G protein/cAMP/adenylate cyclase signaling cascade – leading to gain of function in the affected cells

Unilateral café au lait spots, polyostotic fibrous dysplasia, (multiple osteolytic appearing lesions of the hip and pelvis), precocious puberty, multiple endocrine abnormalities

Only survivable if there is mosaicism

Question 5

Li Fraumeni Syndrome

Answer 5

Li-Fraumeni Syndrome: mutation in TP53 – Autosomal dominant

Multiple cancers: Sarcomas (like osteosarcomas), breast cancer, brain tumors, leukemia adrenocortical carcinoma
(aka SBLA syndrome)

Question 6

Patient presents with HTN, abdominal pain and melena, and muscle pain (myopathy). Muscle biopsy shows transmural inflammation of mid sized arteries with areas of necrosis. What do you suspect? What is this associated with?

Answer 6

Polyarteritis nodosa
vasculitis affecting small and medium vessels in the renal, cardiac, and GI systems (the lungs are classically spared)

o HTN (renal a. involvement), abdominal pain with melena (mesenteric a. involvement), neurologic disturbances and skin lesions

o Transmural inflammation of the arterial wall with fibrinoid necrosis

o Strong association with hepatitis B

Question 7

Patient with a longstanding hx of smoking presents with gangrene of the fingers/toes and autoamputation of one of the fingers. What is the disease and how is the pathology?

Answer 7

Buerger disease:

Segmental thrombosing vasculitis that extends into contiguous veins and nerves—due to direct endothelial toxicity from tobacco or from hypersensitivity to them

Question 8

Involuntary head bobbing

Answer 8

Sign of a widened pulse pressure (usually due to aortic regurg)

o Pulse pressure is proportional to stroke volume and is inversely proportional to arterial compliance

Question 9

Aortic arch derivatives

Answer 9

1st Maxillary artery
1st arch is maximal

2nd Stapedial artery and hyoid artery
Second = stapedial

3rd Common carotid and proximal part of internal carotid
C is the 3rd letter of the alphabet

4th Aortic arch, right subclavian “Four = aor-ta”
“Fours” right subclavian

6th Pulmonary arteries and ductus arterious 66 looks like a pair of lungs

Question 10

Hereditary pulmonary HTN

What is increased?
Treatment?

Answer 10

Hereditary PAH is due to an inactivating mutation in BMPR2 (AD with variable penetrance)

Increased endothelin (antagonize endothelin with Bosentan)

Causes dysfunctional endothelial and vascular smooth muscle cell proliferation → thickening and fibrosis and inc resistance → pulmonary HTN

Can progress to R heart failure (cor pulmonale)

Question 11

MI complications:

Day 1:
Day 1-3:
Day 3-14:
2 weeks-months:

Answer 11

Day 1: ventricular arrhythmia
Day 1-3: fibrinous pericarditis
Day 3-14: free wall rupture. tamponade, LV pseudoaneurysm
2 weeks-months: dressler syndrome, true ventricular aneurysm

Question 12

Noninfectious causes of endocarditis? What will the pathology look like

Answer 12

Malignancy, hypercoagulable states, lupus

Sterile, platelet rich thrombi seen on valve

Question 13

What electrolyte change do you see in myocardial ischemia? How will this look histologically?

Answer 13

Inc intracellular Calcium (lack of O2 means that ATP isn’t being formed, so Na/K ATPase and Na/Ca ATPase can’t work)
Histo: visualization of bands under the microscope: hypercontraction of the sarcomeres due to massive calcium influx

Question 14

Libman-Sacks Endocarditis:

Answer 14

seen in SLE – nonbacterial, verrucous thrombi usually on mitral or aortic valve (LSE in SLE)

Question 15

Progression of stroke histology

Answer 15

1) red neurons (red = dead) - 12 hours
2) Neutrophils - 1 day
3) Macrophages/microglia (days)
4) reactive gliosis and vascular proliferation (1 week)
5) Glial scar (weeks) - liquefactive necrosis

Question 16

What conditions cause O2 to become diffusion limited?

Answer 16

Thickened alveolar capillary membrane (ex. fibrosis)

Dec SA for diffusion (ex. emphysema)

High altitude

Increased pulmonary blood flow (blood moves rapidly through the lung and cannot be completely saturated)

Question 17

CO Poisoning

PaO2:
SaO2:
O2 content:

Answer 17

PaO2: normal
SaO2: decreased
O2 content: decreased

Question 18

Cyanide poisoning:

PaO2:
SaO2:
O2 content:

Answer 18

PaO2: normal
SaO2: normal
O2 content: normal

cyaNide = Normal

Question 19

Anemia

PaO2:
SaO2:
O2 content:

Answer 19

PaO2: normal
SaO2: normal
O2 content: decreased

Question 20

Polycythemia

PaO2:
SaO2:
O2 content:

Answer 20

PaO2: normal
SaO2: normal
O2 content: increased

Question 21

High altitude

PaO2:
SaO2:
O2 content:

Answer 21

PaO2: decreased
SaO2: decreased
O2 content: decreased

“High altitude is decreased”

Question 22

Patient was exposed to a toxic chemical at work and presents with reddish skin discoloration, tachypnea, headache, and tachycardia with N/V, confusion and weakness. He has the smell of bitter almonds on his breath. What was he exposed to and what is the treatment?

Answer 22

Cyanide poisoning

Cyanide inhibits complex IV of the electron transport chain and blocks cellular respiration

Treat with amyl nitrite-
oxidizes ferrous iron (Fe2+) to ferric iron (Fe3+) generating methemoglobin – methemoglobin cannot carry O2 can it has a high affinity for cyanide – it binds and sequesters cyanide in the blood, freeing it from cytochrome oxidase and limiting its toxic effects
Can also use thiosulfate – serves as a sulfar donor to promote hepatic conversion of cyanide to thiocyanate – which is excreted in urine
Can also use hydroxycobalamin (B12 precursor) which generates nontoxic metabolites that are easily excreted in the urine

Question 23

Wilson disease vs Hemochromatosis

Mechanism:
Inheritance:
Parts affected:
Treatment:

Answer 23

Wilson disease:

• accumulation of copper due to impaired excretion
• autosomal recessive
• Liver, eyes, brain, kidney, joints
• chelation with penicillamine

Hemochromatosis:

• accumulation of iron due to inc intestinal absorption
• autosomal recessive
• liver, heart, joints, skin, pancreas
• repeated phlebotomy, chelation with deferasirox

Question 24

Carcinoid syndrome effects on the heart:

Answer 24

can cause formation of valvular fibrous plaques (R>L)

Question 25

Function of and cofactors for pyruvate dehydrogenase

Answer 25

Pyruvate kinase links glycolysis and the TCA cycle Pyruvate → acetyl CoA)

Cofactors = "TLC For Nancy"
Thiamin (B1)
Lipoic acid
CoA (B5)
FAD (B2, riboflavin)
NAD (Niacin, B3)

Question 26

Functions of biotin (B7), What can cause deficiency?

Answer 26

pyruvate carboxylase (gluconeogenesis)
acetyl CoA carboxylase (fatty acid synthesis)
propionyl CoA carboxylase (formation of succinyl-CoA)

Deficiency can be caused by excessive consumption of egg whites

Question 27

Amniotic fluid embolism

Answer 27

o A pulmonary embolism related to pregnancy

Amniotic fluid containing arachidonic acid metabolites is thought to enter the maternal circulation through sites of uterine trauma or cervical lacerations – resulting in an anaphylactoid reaction
o On autopsy will see pulmonary artery branch with swirls of fetal squamous cells
o Can occur during pregnancy or shortly after delivery
o Leads to cardiopulmonary arrest and DIC

Question 28

Mechanism of apoptosis

Answer 28

Bcl2 in the cytoplasm is inactivated, cytochrome c can exit the mitochondria and enter the cytoplasm where it activates caspases that initiate apoptosis

o Caspases are proteolytic enzymes that destroy cell components. They contain cysteine and are able to cleave aspartic acid residues (cysteine-aspartic-acid-proteases)

Question 29

Pathophysiology of atherosclerosis

Answer 29

o Endothelial injury/dysfunction
o Accumulation of LDL within vessel wall
o Macrophages accumulate and transform into lipid laden macrophages (foam cells)
o Release of growth factors by platelets, activated macrophages, and endothelial cells
o Recruitment of T cells and smooth muscle proliferation
o Eventually there is development of a fibrous cap
o *Smooth muscle cells create the fibrous cap: stimulated by PDGF released by platelets

Question 30

Role of kallikrien

Answer 30

Coagulation cascade: accelerates the activation of F12
o Positive feedback: starts being made when there is some F12 present, and then induces more formation of activated F12

Activates bradykinin

Question 31

NF 1 vs NF 2

Answer 31

Type 1 (von Recklinghausen): chromosome 17 (17 letters in von Recklinghausen).
• Café au lait spots, cutaneous neurofibromas (made up of Schwann cells- neural crest origin), pheochromocytomas, Lisch nodule (pigmented iris hamartomas)
• At inc risk of developing CNS neoplasms like meningiomas, astrocytomas, gliomas
• Autosomal dominant with variable expressivity

Type 2: NF2 gene on chromosome 22.
• Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas

Question 32

Friedrich ataxia

Answer 32

degenerative disorder of the cerebellum and spinal tracts
o Autosomal recessive: trinucleotide repeat disorder (GAA) in the frataxin gene that leads to impaired mitochondrial function and free radical damage
o Ataxia, loss of DTRs, frequent falling, diabetes mellitus, hypertrophic cardiomyopathy (common cause of death), pes cavus (high arches)
o Presents in childhood with kyphoscoliosis
o Closely resembles vitamin E deficiency
o Friedrich is your Frat (frataxin) brother: he’s always staggering and falling but has a sweet, big heart