Things to review!! Flashcards
Treatment of psoriasis
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
Xeroderma Pigmentosum
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
Stem cell locations (in skin, bowel, and bone marrow and lung):
skin – basal layer
bowel – mucosal crypts
bone marrow – hematopoietic stem cells
lung – type 2 pneumocytes
McCune Albright Syndrome
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
Li Fraumeni Syndrome
Li-Fraumeni Syndrome: mutation in TP53 – Autosomal dominant
Multiple cancers: Sarcomas (like osteosarcomas), breast cancer, brain tumors, leukemia adrenocortical carcinoma
(aka SBLA syndrome)
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?
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
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?
Buerger disease:
Segmental thrombosing vasculitis that extends into contiguous veins and nerves—due to direct endothelial toxicity from tobacco or from hypersensitivity to them
Involuntary head bobbing
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
Aortic arch derivatives
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
Hereditary pulmonary HTN
What is increased?
Treatment?
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)
MI complications:
Day 1:
Day 1-3:
Day 3-14:
2 weeks-months:
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
Noninfectious causes of endocarditis? What will the pathology look like
Malignancy, hypercoagulable states, lupus
Sterile, platelet rich thrombi seen on valve
What electrolyte change do you see in myocardial ischemia? How will this look histologically?
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
Libman-Sacks Endocarditis:
seen in SLE – nonbacterial, verrucous thrombi usually on mitral or aortic valve (LSE in SLE)
Progression of stroke histology
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
What conditions cause O2 to become diffusion limited?
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)
CO Poisoning
PaO2:
SaO2:
O2 content:
PaO2: normal
SaO2: decreased
O2 content: decreased
Cyanide poisoning:
PaO2:
SaO2:
O2 content:
PaO2: normal
SaO2: normal
O2 content: normal
cyaNide = Normal
Anemia
PaO2:
SaO2:
O2 content:
PaO2: normal
SaO2: normal
O2 content: decreased
Polycythemia
PaO2:
SaO2:
O2 content:
PaO2: normal
SaO2: normal
O2 content: increased
High altitude
PaO2:
SaO2:
O2 content:
PaO2: decreased
SaO2: decreased
O2 content: decreased
“High altitude is decreased”
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?
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
Wilson disease vs Hemochromatosis
Mechanism:
Inheritance:
Parts affected:
Treatment:
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
Carcinoid syndrome effects on the heart:
can cause formation of valvular fibrous plaques (R>L)
Function of and cofactors for pyruvate dehydrogenase
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)
Functions of biotin (B7), What can cause deficiency?
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
Amniotic fluid embolism
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
Mechanism of apoptosis
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)
Pathophysiology of atherosclerosis
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
Role of kallikrien
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
NF 1 vs NF 2
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
Friedrich ataxia
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
