...and going... Flashcards
(263 cards)
1
Q
How does insulin suppress glucagon?
A
Acts directly on alpha cells to inhibit glucagon release
2
Q
Insulin release by? Why? Simultaneous effect on alpha cells?
A
Insulin is release by beat cells. Decreased serum glucose inhibits insulin release and enhances glucagon release. However, increased glucose stimulates insulin release while having little to no effect on glucagon release. Instead, the insulin circles back to inhibit glucagon release as part of its own activity.
3
Q
Myeloid stem cell derivatives?
A
Erythroblast –> RBC
Myeloblast –> Neutrophil, Basophil, Eosinophil
Monoblast –> Monocyte
Mekagaryoblast –> Megakaryocyte
4
Q
Lymphoid stem cell derivatives?
A
B lymphoblast –> Naive B cell –> plasma cell
T lymphoblast –> Naive T cell –> CD4+/CD8+ T cells
5
Q
Cells in the body most sensitive to radiation?
A
Lymphocytes - explains a lot about radiation sickness
6
Q
Immature neutrophils characterized by? Marker? Shift?
A
Decreased expression of Fc receptors (decrease CD16 in left-shifted neutrophils)
7
Q
Cortisol effect on neutrophils?
A
Disrupts integrin holding marginated neutrophils against endothelium –> Increased WBC after steroid injection or in increased cortisol state –> Neutrophil leukocytosis
8
Q
3 causes of eosinophilia?
A
Allergic reaction
Parasitic infection
Hodgkin Lymphoma due to increased IL-5 production
9
Q
Basophilia means?
A
Marker for CML, not entirely clear why
10
Q
Splenomegaly in mononucleosis?
A
CD8+ T cell response (viral infection) –> expansion of white pulp in spleen, specifically the periarterial lymphatic sheath, also see lymphadenopathy –> high white count with atypical lymphocytes
11
Q
mononucleosis misnomer?
A
not monocytes/macrophages –> actually reactive CD8+ T cells
12
Q
negative monospot test? Confirmatory test?
A
Either too early to see positive results, or CMV infection; check for EBV viral capsule antigen
13
Q
Distinguish follicular lymphoma from follicular hyperplasia on histology?
A
hyperplasia –> all follicles in cortex of node (normal)
lymphoma –> follicles invade to paracortex and medulla
14
Q
Tingible body macrophages? Significance?
A
Macrophages in germinal centers consuming dead/apoptotic B cells (normal finding)
t(14;18) –> no apoptosis –> no tingible bodies on histology
15
Q
Marginal zone lymphoma associations?
A
Chronic inflammatory states like Hashimoto’s Thyroiditis, Sjogren’s Syndrome, H. pylori gastritis
16
Q
Two forms of Burkitt Lymphoma?
A
African (endemic) form in jaw - associated with EBV
Sporadic form in abdomen - not associated with EBV
17
Q
Most common form of Non-Hodgkin Lymphoma?
A
Diffuse, large, B cell lymphoma (DLBCL) - clinically very aggressive, can arise via transformation from another lymphoma (not well-understood, EBV may play a role)
18
Q
Name the Non-Hodgkin Lymphomas? (5)
A
1) Follicular
2) Mantle
3) Marginal
4) Burkitt
5) Diffuse, Large, B cell Lymphoma (DLBCL)
19
Q
What defines Hodgkin Lymphoma?
A
Reed-Sternberg cell – isolated – secretes cytokines responsible for B symptoms
20
Q
Cause of B symptoms? Other actions?
A
Reed-Sternberg cell cytokines –> fever, chills, night sweats; also attract reactive lymphocytes, plasma cells, macrophages, eosinophils –> forms the actual lymphoma mass
21
Q
most common Hodgkin Lymphoma?
A
Nodular sclerosing –> lymph node with broad pink bands, lots of fibrosis –> mediastinal LN in young adult
22
Q
Reed-Sternberg cells in big open spaces?
A
Lacunar cells –> diagnosis nodular sclerosing lymphoma
23
Q
Best and worst prognosis Hodgkin Lymphoma?
A
Lymphocyte-rich –> better
Lymphocyte-depleted –> worse
24
Q
Eosinophilia in Hodgkin lymphoma because?
A
Eosinophils are called in by IL-5 (interleukin produced by Reed-Sternberg cell
25
Cytokine that is an important growth factor for plasma cells?
IL-6
26
Bone pain with hypercalcemia? Etiology?
Multiple myeloma -- neoplastic plasma cells activate RANK receptor on osteoclasts
27
Protein bands on gel electrophoresis (normal)?
First and largest band is for albumin. Three small middle bands are alpha-1 antitrypsin, alpha-2 something, and beta something. Last band, bigger than the middle three but smaller than albumin is gamma glubulin, which of course includes all of the immunoglobulins
28
What is an M spike? Usually consists of? Means?
Monoclonal immunoglobulin seen on protein SPEP. Usually IgG, sometimes IgA. Significance is that the patient now has no antigenic diversity, therefore they are prone to infection
29
Protein in urine during multiple myeloma? What about deposition?
Bence-Jones protein, composed of free immunoglobulin light chain. Deposition in kidney tubules --> renal failure (myeloma kidney)
30
M spike with IgM? Clinical findings? Treatment?
Waldenstrom Macroglobulinemia (B cell lymphoma); Clinically, see generalized LAD, visual and neurologic deficits, bleeding, increased blood viscosity (contributes to bleeding); Treat with plasmaphoresis
31
Langerhans cells immunohistochemistry?
CD1a+ and CD100+
32
Type of inflammation in Temporal Arteritis? Treatment?
Segmental granulomatous - see intimal thickening, giant cells; treat immediately with corticosteroids to avert blindness (without even waiting for biopsy confirmation)
33
Granulomatous vasculitis in a young Asian female?
Takeyasu arteritis -- pulseless disease; Treat with corticosteroids
34
Inflammation in polyarteritis nodosa? Disease spares?
Necrotizing vasculitis that spares lungs while involving most other organs
35
"string of pearls" appearance on imaging?
Fibrinoid necrosis after necrotizing vasculitis --> leads to nodular fibrous tissue --> polyarteritis nodosa
36
Preferential artery involved in Kawasaki? Who is affected? Treatment?
Coronary artery (medium vessel disease). Affects young children of Asian descent, usually less than 4 years old; Treat with aspirin to prevent platelet thrombus aggregation via thromboxane A2 inhibition
37
Smoker with autoamputation at fingers and toes? Treatment?
Buerger Disease -- necrotizing vasculitis of digits; Stop smoking (duh), but that won't really bring your fingers back...
38
What is Raynaud phenomenon?
Inappropriate vasospasm of small vessels in digits
39
Vasculitis affecting nasopharynx, lungs, kidneys? Type of inflammation? Antibody finding? Mnemonic?
Wegener's -- necrotizing, granulomatous vasculitis
Remeber We"c"ner's, the "C" shape is a trace through the nasopharynx, lungs, and kidneys (use your imagination); Lab will show C-ANCA (another "C"), and treat with cyclophosphamide (another "C")
40
Patient presents with hematuria, discover increased c-ANCA?
Wegener's granulomatosis --> RPGN, get hemoptosys, bilateral nodular lung infiltrates
41
Lung and kidney involvement, but no nasopharynx, no granulomas? Antibody finding? Treatment?
Think microscopic polyangiitis; looks like Wegener's, but has p-ANCA instead. Treat with cyclophosphamide and corticosteroids
42
Two disorders with p-ANCA? How to distinguish them?
Microscopic Polyangiitis and Churg-Strauss Syndrome
| Churg-Strauss --> asthma, eosinophilia, and granulomas
43
Hematuria and palpable purpura? Treatment?
History of URI, now have IgA nephropathy, Type III immune complex deposition. Self-limited, use steroids if severe. (Henoch-Schonlein Purpura)
44
Two causes of renal artery stenosis?
```
Atherosclerosis (older male)
Fibromuscular dysplasia (younger female)
```
45
Present with headache, papilledema, signs of acute renal failure?
Malignant hypertension or hypertensive crisis
46
Part of vessel affected in atherosclerosis? Composition? Most commonly affects?
Intimal plaque that obstructs blood flow; has a necrotic lipid core (maybe calcified) under a fibromuscular cap --> primarily large and medium-sized arteries including abdominal, coronary, popliteal, internal carotid
47
How much stenosis is necessary for clinical symptoms?
> 70% occlusion before symptomatic
48
Symmetric thickening of blood vessel with pink hyaline in the wall? Two causes?
Hyaline areteriolosclerosis
1) Benign hypertension (reactive process)
2) Diabetes (non-enzymatic glycosylization)
49
Patient with PAH is waiting for a lung transplant. Medication to help them in the meantime? MoA?
Vasodilator - Bosentan is an endothelin-receptor antagonist that blocks the effects of endothelin, decreases pulmonary arterial pressure and lessnes the progression of vascular and right ventricular hypertrophy. (i.e., it halts progression to cor pulmonale)
50
How does Bosentan work?
Competitive antagonist of endothelin receptors, used to treat idiopathic pulmonary hypertension and prevent cor pulmonale.
51
Describe how insulin transmits signal to cell?
Insulin receptor has intrinsic tyrosine kinase activity --> tyrosine phosphorylation of Insulin Receptor Substrate. IRS follows two paths: PI3K pathway stimulates glycogen, lipid, and protein synthesis, while RAS/MAP kinase pathway stimulates cell growth and DNA synthesis
52
T-helper 1 and T-helper 2 cells are what kind of T cells?
CD4+ T-helper cells
53
TH1 cells secrete what? Why?
TH1 cells secrete gamma-interferon, IL-2, and other lymphokines to activate macrophages and stimulate CD8+ cytotoxic T-cells - contribute to cell-mediated adaptive immunity (targets intracellular pathogens) and Type IV delayed hypersensitivity reactions.
54
TH2 cells secrete what? Why?
TH2 cells secrete IL-4 and other lymphokines to stimulate B-cell antibody production as part of humoral adaptive immunity. Also release IL-13 which, together with IL-4, preferentially promotes B-cell IgE production (class-switching). TH2 cells also help to activate eosinophils by secreting IL-5.
55
Who secretes IL-1? Why?
Macrophages - stimulate helper T-cells
56
Who secretes IL-3? What does it do?
Helper T-cells secrete IL-3, recruits bone marrow stem cells.
57
What does gamma-interferon do?
mainly activates macrophages
58
Where do meningococci (i.e., N. meningitidis) gain entry to human host? Then where?
Transmission occurs through exposure to respiratory droplets or direct contact with respiratory secretions. Meningococci then attach to and colonize the pharynx via pilus-mediated adherence to mucosal epithelial cells. They subsequently invade the epithelium and gain access to the vasculature where they can spread hematogenously. Pili may also play a role in the ability of meningococci to cross the blood-brain-barrier and interact with meningeal tissues.
59
Common mutations causing Ehlers-Danlos Syndrome phenotypes?
Deficiencies of the lysyl hydroxylase and procollagen peptidase enzymes responsible for collagen synthesis.
60
Pregnant woman has evidence of hematoma between placenta and uterine wall on ultrasound? Complication? Also see?
Placental abruption - Watch for DIC due to release of tissue factor into maternal circulation (high concentration of tissue factor in the placental trophoblast). Also find uterine tenderness and vaginal bleeding, not to mention losing the fetus.
61
Origin of the spots in turberculoid leprosy?
Artifacts of immunological warfare! Patients with tuberculoid leprosy develop a strong TH1-mediated response in affected tissues, leading to the activation of macrophages that kill M leprae organisms, thereby limiting disease extent. However, this localized inflammation damages the skin an cutaneous nerves, leading to the development of a small number of hypopigmented, well-demarcated plaques with decreased sensation.
62
Who calls in IL-4, IL-5, and IL-10 to fight infection?
TH2 cells.
63
Two blood vessels that can negatively affect CN III?
The third nerve courses between the posterior cerebral and superior cerebellar arteries as it leaves the midbrain, and is susceptible to injury from an expanding aneurysm originating from those vessels. Chronic smoking and poorly controlled hypertension are risk factors for developing intracranial aneurysms.
64
Mechanism of amenorrhea in anorexia?
Functional hypothalamic amenorrhea - underlying pathophysiology appears to involve reduced circulating leptin levels as a result of diminished adipose tissue stores. The decrease in leptin inhibits pulsatile gonadotropin-releasing (GnRH) hormone from the hypothalamus, causing decreased pituitary LH and FSH secretion, low circulating estrogen levels, and amenorrhea.
65
Long-term complication of Functional Hypothalamic amenorrhea?
Reduced peak bone mass --> early-onset osteoporosis
66
Someone has functional hypothalamic amenorrhea with normal BMI?
Probably an athlete, the BMI is not indicative of the balance between calories consumed and calories expended. Regular total body mass with no fat stores still means decreased circulating leptin --> decreased pulsatile GnRH release --> FHA.
67
What exactly does hepatitis D virus need from hepatitis B virus?
Hepatitis D Antigen (HDAg) must be coated by the external coat hepatitis B surface antigen of HBV (HBsAg) in order to penetrate the hepatocyte. Therefore, hepatitis D cannot directly infect hepatocytes, it must have help from hepatitis B in order to be infective.
68
Hepatitis D looks like what?
Double-shelled particle that resembles the Dane particle of hepatitis B virus - this must be how it manages to get the HBsAg to help it out, tricks HBV.
69
Valproate indication and MoA?
Anticonvulsant (absence, general tonic-clonic, and myoclonic) and mood stabilizer (acute mania and maintenance of bipolar disorder); Blocks voltage-gated sodium channels and enhances GABA synthesis and release.
70
Young child has history of fever, now has lacy rash all over that spares the face. Diagnosis?
Check the fever history:
High-grade --> Roseola, HHV-6 infection of CD4+ T cells
Low-grade --> Erythema infectiosum (fifth disease) caused by parvovirus B19, infection of erythrocyte precursors in the bone marrow.
Also, check for mention of flushed cheeks --> parvovirus B19 ("slapped cheek" appearance)
71
Cellular receptor for parvovirus B19?
Blood group P antigen (globoside), erythrocytes in the bone marrow.
72
When should the vitelline duct obliterate? If it doesn't? (4)
During the 7th week of embryonic development.
1) Persistent vitelline duct (vitelline fistula)
2) Meckel diverticulum
3) Vitelline sinus
4) Vitelline duct cyst
73
Source of alkaline phosphatase during bone remodeling? Other sources?
Osteoblasts. Also released into circulation by the placenta in pregnant women, the liver, and the intestine.
74
Alkaline phosphatase level is elevated. How to know if this is due to bone remodeling or some other process?
The two predominant contributors of alkaline phosphatase - liver and bone - can be differentiated in several ways, including electrophoresis, use of specific monoclonal antibodies, and through denaturation test (bone-specific alk phos is easily denatured by heat, bone = boil)
75
If an underlying malignancy is responsible for a presentation of dermatomyositis, what other cancers would be expected?
Ovarian, lung, colorectal, and non-Hodgkin lymphoma
76
Definitive treatment for carcinoid syndrome? In the meantime?
Surgical excision of tumor. In the meantime, treat with octreotide, a somatostatin analog that acts on somatostatin receptros and inhibits secretion of many hormones and hormone-like substances. Also good for VIPomas for the same reasons.
77
Theophylline indication, MoA, SE?
Theophylline is an adenosine receptor antagonist and phosphodiesterase inhibitor that is sometimes used as an alternate therapy for asthma and chronic obstructive pulmonary disease. It causes bronchodilation primarily by increasing intracellular cyclic AMP levels (similar to beta2-adrenergic agonists) and also has mild anti-inflammatory effects. Hepatic metabolism, so watch out for CYP450 inhibitition --> exceed therapeutic index --> excessive CNS stimulation (tremor, seizures), gi disturbance, cardiovascular abnormalities.
78
Flurorquinolone that inhibits CYP450?
Ciprofloxacin (this isn't in Sketchy)
79
Squishy, pearlescent goop accumulated in the middle ear? Clinical finding?
Cholesteatoma - collection of squamous cell debris. Can be congenital or secondary. Patient will present with painless otorrhea and conductive hearing loss. Eventually can cause vertigo or facial palsies.
80
Primary HSV-1 versus reactivation?
Primary will be accompanied by more painful vesicles and ulcers (as in gingivostomatitis), while reactivation will be mild, unilateral, and limited to the lips
81
Immunohistological marker for Schwannoma?
S-100 positive (neural crest origin)
82
Bullous pemphigoid is caused by?
Antibodies against hemidesmosomes along the basement membrane of the dermal-epidermal junction.
83
Uniformly enlarged versus irregularly enlarged uterus?
Uniform enlargement suggests adenomysis
| Irregular enlargement suggests leiomyoma
84
Middle-aged woman presents with recent heavy and painful menstrual cycles, enlarged uterus, not pregnant?
Adenomyosis - presence of endometrial glandular tissue within the myometrium.
85
Painful hemorrhoids - nerve implicated?
Pudendal
86
What component of the extracellular matrix serves as the binding point for cells?
Adhesion of cells to the extracellular matrix involves integrin-mediated binding to fibronectin, collagen, and laminin.
87
How could you get a right-sided varicocele? Significance?
This isn't going to be nutcracker syndrome, so think of something like a renal vein thrombosis. Of course, the thrombosis can happen on the left side, too. Significantly, a right-sided varicocele would indicate concern for thrombosis progressing to the IVC, or generally indicate a hypercoagulable state.
88
Stable angina presentation?
```
20 minutes (irreversible injury)
ST segment depression, shortness of breath
```
89
Where is damage in angina/ischemia?
Subendocardial region, between endocardium and myocardium --> furthest from any blood supply, first to suffer ischemia, insufficient O2 diffusion
90
Unstable angina?
Usually plaque rupture, partial occlusion
| - chest pain at rest, reversible injury progresses to MI and ST elevation
91
ST depression?
subendocardial ischemia, reversible injury to myocytes
92
chest pain unrelated to exercise?
Prinzmetal angina or unstable angina
93
ST segment elevation?
Transmural damage (not subendocardial) --> indicates MI
94
Chest pain, symptoms not relieved by nitroglycerin? Other symptoms?
Myocardial infarction due to complete occlusion of coronary vessel; Also have dyspnea, diaphoresis
95
LAD occlusion impact on cardiac wall?
Left anterior portion and anterior 1/3 of interventricular septum
96
Right coronary artery occlusion impact?
Posterior wall of left ventricle and posterior 2/3 interventricular septum - also, this is the only artery supplying the posteromedial papillary muscle --> rupture/mitral valve failure
97
Left circumflex artery occlusion impact?
Lateral wall of left ventricle
98
MI serum markers?
Troponin I - most sensitive, quick on (2 hours), stays on for 7-10 days
CK-MB - slower, seen 4-6 hours after infarct, peaks at 24 hours, gone by 72 hours (useful as marker for re-infarct)
99
Treatment for MI (medical)? Definitive treatment?
Aspirin/heparin; supplemental O2; nitrates; beta-blocker; ACE inhibitor. Definitive treatment is fibrinolysis or angioplasty
100
complications of fibrinolysis and angioplasty?
Return Ca++ to damaged area --> muscle cells contract (even though dead) --> contraction band necrosis
Return O2 --> generate free radicals --> further injury
101
Three phases post MI?
coagulative necrosis --> 4-24 hours (1 day)
inflammation --> 1-7 days (neutrophils, then macrophages, 1 week)
healing --> weeks to months (form scar)
102
which papillary muscle is most likely to rupture after MI? Why?
Posteromedial - only supplied by one artery, the Right Coronary Artery (RCA)
103
anterolateral papillary blood supply?
Two (!) -- LAD and LCX
104
Dressler syndrome has antibodies against?
Pericardium
105
Timeline for free wall rupture?
4-7 days post-MI, due to macrophage activity
106
cause of death in "sudden cardiac death"
Ventricular arrythmia
107
Crackles in the lungs suggest?
Pulmonary congestion
108
CHF means? Exacerbates? Treatment?
Decreased forward perfusion; body responds with RAAS activation, exacerbating problem; mainstay of treatment is ACE inhibitor
109
Clinical features of CHF?
Pitting edema, liver cirrhosis, JVD, SoB
110
What do you see on gross exam of cirrhotic liver due to CHF?
"Nutmeg" liver, bunches of small hemmhorages that look like polka dots or the cross-section of a nutmeg. Also called cardiac cirrhosis
111
Most common congenital heart defect? Associated with?
VSD - associated with fetal alcohol syndrome
112
Septal defect associated with Down's Syndrome?
ASD --> ostium primum
113
Clinical findings on auscultation of ASD? Why? Another way to get this sign?
Split S2 - due to extra volume in RA, delayed closure of pulmonic valve. You can also overload the RA if the tricuspid valve is leaky.
114
Parodoxical embolus?
embolic mass passes through an ASD directly to the systemic circulation, bypassing the lungs
115
PDA treatment, MoA?
Indomethacin --> decreases Prostaglandin E (PGE "keeeps" the DA open)
116
boot-shaped heart on x-ray of a child?
Tetralogy of Fallot (ding, ding!)
117
transposition of great vessels association?
maternal diabetes
118
two markers for previous strep infection?
anti-streptolysin O (ASO)
| anti-DNase B (dornase)
119
strep capsule is made of? Significance?
Hyaluronic Acid - important because it is anti-immunogenic, since we have endogenous hyaluronic acid
120
strep pyogenes exotoxin?
SpeA and SpeC are superantigens --> TSLS
| SpeB --> protease --> necrotizing fasciitis
121
Death during strep infection?
Acute Rheumatic Fever --> myocarditis --> see Anitchkow cells (caterpillar nucleus) on histopathology
122
"fish-mouth" appearance of aortic valve?
Chronic Rheumatic Fever --> fusion of commisures --> aortic stenosis --> predisposition to infective endocarditis
123
murmur associated with aortic regurgitation?
"blowing diastolic" murmur as blood flows backwards into left ventricle during diastole
124
Bounding pulses, pulsatile nailbed? Pathology finding?
Hyperdynamic circulation, indicates aortic regurgitation. Results in increased systolic pressure and decreased diastolic pressure. On autopsy, find eccentric hypertrophy of the heart
125
Cause and consequence of volume overload of the left atrium?
Caused by mitral regurgitation --> pulmonary congestion, pulmonary HTN, atrial fibrillation (edema, SoB, heart failure cells)
126
Atrial fibrillation is due to?
Abnormalities of conduction, perhaps caused by dilation, hypertrophy, scarring, etc.
127
Endocarditis negative bacteremia?
Remeber HACEK organisms --> Hemophilis, Actinobacilis, Cardiobacterium, Eikenella, Kingella (hard to grow)
128
Lab findings in infectious endocarditis? Next test?
Positive culture and anemia of chronic disease (microcytic anemia, increased hepcidin, decreased TIBC, etc). Next do trans-esophageal echocardiogram (TEE) to detect valve lesions
129
Non-infective endocarditis?
Sterile vegetations associated with hypercoagulable state such as SLE or underlying adenocarcinoma --> mitral valve involvement
130
Describe finding of endocarditis in a patient with SLE?
Libman-Sacks endocarditis --> small vegetations on both sides of mitral valve.
131
Most common cause of hypertrophic cardiomyopathy? Actual cause of death?
Genetic mutations in sarcomere (autosomal dominant); Ventricular arrhythmias due to hypertrophy
132
Biopsy of cardiac hypertrophy shows?
Myofiber hypertrophy with disarray (non-parallel myocytes)
133
Causes of restrictive cardiomyopathy (5)?
1) Amyloidosis
2) Sarcoidosis
3) Hemochromatosis
4) Endocardial fibroelastosis (children)
5) Loeffler syndrome --> eosinophilic infiltrate --> fibrosis of endocardium and myocardium
134
EKG shows low voltage and diminished QRS?
Restrictive cardiomyopathy
135
Most common primary tumor of heart in adults? Presentation?
Cardiac myxoma --> tumor of mesenchyme
| Presents with syncope as the pedunculated mass in the atrium blocks flow through the mitral valve
136
Most common primary tumor of heart in children? Association?
Rhabdomyoma (not rhabomyosarcoma, that would be malignant) --> benign striated muscle tumor in ventricle; Associated with tuberous sclerosis
137
Analysis technique to identify DNA binding proteins?
Southwestern Blot (combination of protein (Western Blot) and DNA (Southern Blot)) --> Looks like all the others, but after separating the protein via electrophoresis/nitrocellulose gel, add radiolabeled DNA --> binds at the protein's regulatory sequence, just as the protein would normally do in vivo if it were that kind of protein
138
Patient needs anticoagulation, but heparin is not an option. Other choices?
Think of the Big Gators, the direct thrombin inhibitors: Argatroban, Dabigatran, Bivalirudin
139
Name two alternatives to unfractionated heparin, and discuss HIT, pregnancy?
1) Low Molecular Weight Heparin (LMWH) (some antiplatelet activity, less likely than UF)
2) Fondaparinux (no antiplatelet activity)
Use unfractionated heparin during pregnancy
140
Only statin drug not hepatically metabolized?
Pravastatin
141
SE of statin medications?
Myopathy, see elevated CK
mild LFT elevation
teratogenic
142
Which Apo receptor is on chylomicrons going from gut to liver? Via? Mechanism of uptake?
Apo E, gets to circulation via lymphatic system. Endocytosis ("E" for "E"ndocytosis)
143
Which Apo receptor does the liver recognize on VLDL and LDL?
Apo B
144
What is LCAT?
lecithin:cholesterol acyltransferase --> converts free cholesterol to cholesterol esters for reverse cholesterol transport in HDL
145
Patient with multiple dyslipidemias, smoker, previous MI, low HDL, etc, what medication will lower risk of future adverse events?
Statin drug, even if the LDL isn't so bad. Drugs to raise HDL have not panned out to prevent adverse cardiovascular events as effectively as statins.
146
LDL receptor effect of stating drugs?
Statin drugs disrupt HMG CoA-reductase, decreasing cholesterol synthesis in the liver. In response, the liver upregulates expression of LDL receptors, extracting more LDL particles out of the blood.
147
Second line treatment after statins to reduce cholesterol levels? Notable SE and interactions?
Cholestyramines - bind cholesterol into insoluble resins that are excreted. Ramps up HMG Co-A reductase. Decreases fat absorption --> steatorrhea, reduced absorption of vitamins A, D, E, and K --> coagulation abnormalities, especially if also on Warfarin already.
148
Enzyme that makes triglycerides useful as an energy source? Location?
Lipoprotein lipase - attached to the luminal surface of capillaries in extrahepatic tissues - converts triglycerides to free fatty acids
149
Most effective agent for raising HDL? Warn patient about?
Niacin - up to 30% increase. However, patients report a burning sensation and cutaneous flushing upon administration, thought to be mediated by prostaglandins. Can take aspirin to avoid this SE.
150
Contraindications for Niacin?
Hyperglycemia - not good for diabetics
| Hyperuricemia - not good for gout-predisposed
151
Patient is started on niacin. Why? What needs to be monitored?
Niacin is the most effective agent for raising HDL. However, need to monitor liver function, watch for elevated ALT/AST, discontinue to avoid liver toxicity.
152
HDL is secreted from where? Goes where? Does what? Binds where/how?
Nascent HDL secreted from liver and intestine, extracts cholesterol from peripheral tissue, returns to liver to deliver cholesterol via the Scavenger 1 receptor.
153
Drug that blocks intestinal absorption of cholesterol? SE?
Ezetimibe - watch out for diarrhea/steatorrhea.
154
Patient has high cholesterol, so you start a medication. The patient develops gall stones. Story? Other unfortunate side effect?
Bile acid resins bind bile salts, leading to excretion (this is how the drug works to lower cholesterol). In response, the liver ramps up cholesterol production, and more cholesterol ends up in the biliary tract, potentially leading to gall stones.
Patient will also likely show higher circulating triglycerides
155
Two dyslipidemia drug classes causing cholesterol gall stones?
Fimbrates and cholestyramines
156
p53 gene located where? What other important gene is here?
17 - also home to RARA, the Retinoic Acid Receptor Alpha gene of t(15;17) APML fame; also home to BRCA-1
157
Enzyme that catalyzes the first step in the arachidonic acid pathway?
Pholspholipase A2 (PLA2) --> hydrolyzes AA from the cell membrane
158
two molecules that cause vasoconstriction?
endothelin and thromboxane A2 (TXA2)
159
site of COX-2 expression?
vascular endothelial and vascular smooth muscle
160
PGI-2 synthesized by? Does what?
COX-2 -- vasodilation
161
Which COX produces TXA2? Implication?
COX-1; not blockable by COX-2 inhibitors such as celecoxib and acteamenophen, can spare gastric prostaglandin synthesis, good for PUD
162
allopurinol alternative? Does what?
febuxostat -- inhibits xanthine oxidase
163
Why are allopurinol and febuxostat initiated with concurrent NSAID?
allopurinol and febuxostat can precipitate gout attack with initiation of treatment, always cover intro with NSAID
164
Alternate use for allopurinol beyond gout?
Manage tumor lysis syndrome; manage purinol overload from Lesch-Nyhan
165
Allopurinol SE (3)?
potentiate chemotherapeutic agents via purinol pathway inhibition; Stephens-Johnson Syndrome; DRESS Syndrome --> eosinophilia
166
probenecid uses?
Stop renal excretion of penicillin, stop renal reabsorption of uric acid (hydrate to avoid renal stones)
167
very high dose aspirin does what?
prevents reabsorption of uric acid (acts like probenecid, also decreases excretion of penicillin)
168
abdominal discomfort plus mouth lesions instead of anus? Chromosome, defect, sequence?
Peutz-Jegher's Syndrome; Chromosome 19, serine/threonine kinase abnormality --> intussusception/obstruction
169
multiple mitoses means?
upgrade to malignancy
170
what does a lipoblast look like on histology?
round, clear, non-membrane-bound cytoplasmic lipid
171
Asboe-Hansen sign? Means? Histology?
Push on a bullae, see it extend into surrounding skin --> suggests Pemphigous Vulgaris; auto-antibodies against desmogleins (desmosomes) between adjacent keratinocytes; basement membrane hemidesmosomes not affected
172
Surfactant is primarily produced by?
Type II pneumocytes
173
Unilateral sympathetic disruption of head and neck in smoker?
Pancoast Tumor --> Horner's Syndrome --> compression of cervical ganglion
174
Parkinsonian tremor in alcoholic due to?
Alcoholic cerebellar degeneration due to thiamine deficiency
175
Brisk rectal bleed in otherwise well-appearing 2-year old? Histology? Pain level?
Meckel Diverticulum (Rule of Twos); See heterotopic gastric mucosa and pancreatic tissue mixed into normal intestinal mucosa; anemia due to painless hematuria
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Histology of Crohn's?
Transmural inflammation
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Mutation in hypertrophic cardiomyopathy? Who?
beta-myosin heavy chain protein; adolescents/young adults; multi-factorial disease
178
auscultation of HCM?
Systolic crescendo-decrescendo between apex and left sternal border, radiates to suprasternal notch
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identify closing of aorta on venous trace?
bump in aortic pressure, occurs before diastole starts (i.e., well before mitral and tricuspid valves open)
180
most common primary immune deficiency? Symptoms? Due to?
Selective IgA deficiency; No IgA --> respiratory and GI tract (mucosal) infections; Due to impaired B cell differentiation into IgA-secreting plasma cells
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DNA synthesis occurs in which direction?
5' -> 3'; note that template is "read" from 3' -> 5' direction, but synthesis of new strand is the complementary 5' -> 3'
182
Pathogenesis of hereditary cancer syndromes?
Autosomal Dominant; only RET (MEN2) is due to gain of function - all others (APC, VHL, TP53, MEN1) are due to loss of function mutations
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What are the hereditary mismatch repair genes?
MSH2, MLH1, MSH6, PMS2 --> microsatellite instability
184
Drug to avoid in Parkinson's patients? Why? When is this drug normally indicated?
Metoclopramide --> exacerbates symptoms or triggers EPS via dopamine receptor antagonism (tardive dyskinesia);
Metoclopramide normally used to relieve nausea/vomiting, or to speed stomach transit of contents post-surgery or in cases of diabetes with stomach dismotility
185
Abnormal component of urine that darkens on exposure to O2? Means? Sequelae?
Homogentisic acid --> Alkaptonuria --> defect in homogentisic acid dioxygenase --> ochronosis and osteoarthropathy (discolors skin and cartilage, causes long-term damage); Should see urine sign first, but they could slip in a blackened joint as an "indicentaloma" and ask what's going on
186
photomicrograph shows protein accumulation next to glomerulus?
might be stored renin in the juxtaglomerular cells
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Three ways to release renin?
Macula densa detects decreased tubular NaCl
Decreased pressure in afferent arteriole
Sympathetic stimulation
All three result in release of pre-formed renin
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Location of macula densa cells?
Distal convoluted tubule, adjacent to afferent and efferent arterioles
189
Lens dislocation direction in hereditary conditions? Inheritance patterns?
```
Marfan Syndrome (AD) --> upward dislocation
Homocystinuria (AR) --> downward dislocation
```
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Abdominal cross section on CT shows an organ with bright spots?
Calcifications --> pancreatitis or other pancreatic disorder like pseudocyst; organ may be enlarged or otherwise displaced
191
Why is heparin safe in pregnancy? Warfarin?
Heparin is a negatively charged molecule, and is therefore water soluble --> cannot cross placental membrane; Warfarin is bound to albumin, gets transported across the placenta --> teratogenic
192
Motivational interviewing involves? Stage of change where effective?
Encourage the patient's own positive motivations for change (don't lecture or impose); psychotherapy for patients who are not ready to change, i.e., quitting smoking
193
Impaired exercise tolerance in a healthy adolescent? Details?
Consider McArdle Disease - autosomal recessive type V glycogen storage disease; deficiency of muscle glycogen phosphorylase; impaired glycogenolysis --> no glycogen degradation to glucose 1-phosphate
194
Appearance of "U" waves and ST segment depression on EKG? Opposite?
Hypokalemia; hyperkalemia --> peaked T waves
195
Endocrine gland releasing melatonin? Does what?
Pineal gland; modulate circadian rhythms in response to darkness or sympathetic stimulation
196
Signs of pinealoma? Nerve effect? Syndrome?
Pineal gland tumor --> obstruct cerebral aqueduct --> hydrocephalus --> nausea/vomiting/headaches; compress superior colliculus --> upward gaze palsy, impaired convergence, absent pupillary light reflex --> Parinaud Syndrome
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CAAT Box? Another one?
highly-conserved sequence that functions as a promoter of transcription in eukaryotes; TATA box -both bind transcriptiong factors and RNA polymerase II (--> mRNA)
198
cirrhotic liver from any cause - what cells make up the nodules?
proliferating hepatocytes
199
PID sequelae? History?
Ectopic pregnancy and infertility due to fallopian tube damage; History of unprotected sex, multiple partners, 15-25 years of age
200
large doughy mass above left clavicle that transilluminates? Genetics? Inheritance?
Cystic hygroma - painless - lymphatics not properly connected to venous system -- Seen in Turners, Trisomy 13/18/21 (any chromosomal aneuploidy)
201
raised erythematous spots and streaks after a hike in the woods?
poison ivy or poison oak (the streaks are from brushing contact); Type IV hypersensitivity cell-mediated reaction
202
Describe rash of Rocky Mountain Spotted Fever
petechial rash on ankles and wrists, spread to trunk, palms, soles
203
mechanism of diarrhea in lactose intolerance? Younger vs older?
Osmotic diarrhea; expression of lactase gene declines steadily in most ethnic groups (normal change)
204
Damage to the amygdalae, perhaps after encephalitis of temporal lobe? Implicated organism?
Impaired memory formation, oral fixation, hypersexuality, Kluver-Bucy Syndrome; HSV-1 encephalitis can be a trigger, since it attacks the temporal lobes
205
low back pain red flags (7)? Treatment plan?
Age > 50, history of cancer, constitutional symptoms, pain interferes with sleep, duration > 1 month, neurologic deficits, no response to therapy; Start with NSAIDS, then assess
206
cyclosporine - use and MoA?
immunosupressant - inhibits IL-2 transcription --> limits growth/differentiation of T-cells to enhance graft acceptance
207
long-time psych patient now shows symptoms of movement disorder?
Tardive dyskinesia; lont-term blockade of dopamine receptors leads to upregulation and compensatory supersensitivity of dopamine redceptors; discontinue medication (1st gen antipsychotic, probably), switch to 2nd gen like clozapine or quetiapine
208
feedback mechanism in contact inhibition?
epithelial cells don't grow onto each other in a petri dish (or in your body) - mitosis stops when cadherins and catenins give negative feedback; uninhibited growth --> malignancy
209
which polio vaccine can revert?
Oral polio vaccine is attenuated, but can revert to virulence
210
Benefit of oral polio vaccine?
Induces IgA mucosal immunity
211
As renal perfusion pressure drops (i.e., stenosis of renal artery), what happsn to GFR, FF, RPF?
Autoregulation kicks in --> constriction of efferent arteriole improves glomerular filtration rate (GFR) at the expense of renal plasma flow (RPF); filtration fraction FF = GFR/RPF, which actually rises during underperfusion. So GFR and RPF may decrease, but ratio increases because GFR decreases more, relatively
212
major cause of orthostatic hypotension in the absence of trauma (i.e., not volume-depleted)
Inadequate compensatory stimulation via alpha-1 adrenergic receptors (tilt-test)
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Woman with a skin condition gets a warning about pregnancy - what meds? Examples?
Vitamin A derivatives (retinoids) are teratogenic; Retin-A, Actretin, etc.
214
Penicillin-aminoglycoside synergy?
Some bacteria resist aminoglycoside via poor drug penetration; disrupt cell wall with penicillin and BOOM!
215
orlistat MoA?
inhibits intestinal lipase --> "improved transit"
216
findings on kidney biopsy using Jones-methanamine silver stain?
Membranous nephropathy --> dark staining "spikes" are normal glomerular basement membrane (GBM), while pale, non-staining areas are immune complex deposits; nephrotic syndrome, proteinuria > 3.5g/day
217
Significance of the dentate line for circulatory system? Cancer?
Dentate line is the distal end point of the endoderm-derived rectum --> drains via the superior rectal vein to the inferior mesenteric vein and the hepatic portal system --> cancer metastasizes to the liver
Beyond the dentate line is ectoderm-derived anus, which drains via the inferior and middle rectal veins to the internal iliac vein and the caval system --> cancer metastasizes to systemic targets
218
Hormones released in response to starved state?
Glucagon and epinephrine --> increased gluconeogenesis
219
sugar at the center of glycolysis/gluconeogenesis?
Fructose-6-phosphate
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Enzymes acting on fructose-6-phosphate? Regulated by?
Fructose-6-phosphate (F6P) --> Fructose-2,6-bisphosphate via Phosphofructokinase - driven by insulin (decreased cAMP);
Fructose-2,6-bisphosphate --> Fructose-6-phosphate via Fructose-2,6-bisphosphatase - driven by glucagon (increased cAMP)
221
tug-of-war over glucose?
Glucagon drives gluconeogenesis: Fructose-2,6-bisphosphate gets pushed towards fructose-6-phosphate (F-6-P glucose and pyruvate);
Insulin drives glycolysis: Stimulates Phosphofructokinase 2 to push away from fructose-6-phosphate (further from glucose)
222
Why is the cavernous sinus unique?
Only venous sinus to receive venous blood from facial (ophthalmic) and cerebral veins --> spread of infection from face to brain, such as in mucomycosis
223
mumps infection, now no sex drive?
Swelling of testis --> seminiferous tubule atrophy --> infertility, Leydig cell atrophy ( --> decreased testosterone) --> treat with exogenous testosterone until recovered and able to bone as usual
224
stool examination shows trophozoites that ate RBCs? Transmission? Colonoscopy?
Entamoeba hystolitica; fecal-oral transmission; See "flask-shaped" ulcers on colonoscopy
225
Insulin trigger prior to increased blood glucose? Such as?
Incretins - GI hormones produced by gut mucosa; Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)
226
2 different Apo-B proteins? Relationship?
ApoB-100 --> synthesized in liver
ApoB-48 --> synthesized by intestinal enterocytes, packaged into chylomicrons
ApoB-48 is a truncated version of ApoB-100, made by switching one residue to introduce a stop codon in the mRNA transcript (normal physiology)
227
who coordinates vomiting response? Sources of input (3)?
Nucleus tractus solitarius. Receives input from:
1) stomach via vagus nerve - 5HT3 (serotonin)
2) vestibular system via CN VIII
3) area postrema (chemoreceptor trigger zone) - outside BBB in 4th ventricle
228
Ondansetron MoA, SE?
Antagonize 5HT3 on CTZ; constipation (anti-serotonin), HA/confusion, prolong QT --> torsades de pointes, serotonin syndrome
229
vestibular motion sickness treatment? SE? Alternative?
1st generation H1 receptor blockers - diphenhydramine, meclazine (crosses BBB) and antimuscarinic sedation; Also can treat motion sickness with scopalomine, M1 antimuscarinic
230
area postrema receptors? What about in the gut?
D2 - block with metoclopramide, but watch EPS; Also used to treat gastroparesis
231
Metoclopramide SE?
lethargy, EPS (tardive dyskinesia), NMS, increase prolactin, torsade de pointes
232
source of histamine targeting parietel cells? Powered by?
enterochromaffin-like cells activate parietal cell secretion when triggered by gastrin from G cells located in the antrum of the stomach
233
Gastrin released where?
gastrin released into blood (not stomach) in response to signal
234
direct stimulation of parietal cells?
acetylcholine via M3 receptor via vagus nerve
235
vagus nerve stimulates parietal cells how?
releases gastrin-releasing peptide
236
"-tidine" drugs? Examples? Indication?
H2 receptor blockers; ranitidine, cimetidine, famotidine, nizatidine - primarily inhibit nocturnal secretion of H+, not as usefule for acute attacks
237
cimetidine SE?
anti-androgenic --> gynecomastia, impotence, increased prolactin; Also trashes CYP450
238
PPI risk?
C. diff, CA/nosocomial pneumonia, decreased divalent cation absorption (Ca++, Fe++, Mg++)
239
senna use? SE?
stimulant laxative, 6-12 hours for effect (cathartic laxative); SE is malanosis coli --> brown pigmentation of colon
240
mu-opioid agonists to block diarrhea? Contraindications?
loperamide, diphenoxylate; not for bloody diarrhea, inflammation, fever
241
sympathetic activation of insulin release?
beta-2 adrenergic (Gs, increased cAMP)
242
mechanism of insulin release from beta cells?
ATP-dependent K+ channels close --> beta cells depolarize --> voltage-gated Ca++ channels open --> Ca++ influx --> insulin secretion via preformed granules, along with C peptide
243
clever treatment for hyperkalemia?
IV insulin (add glucose to prevent hypoglycemia) --> drives K+ into cells
244
diabetes meds for Type 1 diabetes (three classes)? Why?
Type 1 means no insulin being produced, must give exogenous
1) short acting - glulisine, aspart, lispro
2) medium acting - regular insulin, NPH
3) long-acting - detemir, glargine
245
sulfonylurea MoA?
binds ATP-dependent K+ channels on beta cells --> release endogenous insulin
246
Second generation sulfonylurea drugs? What about someone with a sulfa allergy? Both require?
glyburide, glimepiride, glipizide
non-sulfa, same MoA -- meglitinides (repaglinide, nateglinide)
Both of these classes require endogenous insulin production in the beta cells to be effective
247
GLP-1 agonists
linaglutide, examatide --> activate GLP-1 receptor --> increased insulin release and satiety, decrease glucagon release (decrease gluconeogenesis) and gastric emptying
248
Diabetic insulin-releasing drug whose effect tapers as glucose levels normalize?
GLP-1 agonists --> no hypoglycemia
249
manage diabetes by inhibiting glucagon?
DPP-4 inhibitors --> increase incretin levels --> inhibit glucagon release --> decrease gastric emptying and decrease blood glucose
250
Metformin MoA (2)? General action? Drug class?
1) inhibits mitochondrial enzyme glycerophosphate dehydrogenase --> decrease hepatic gluconeogenesis
2) activate enzyme AMP-activated protein kinase (AMPK) --> decrease gluconeogenesis, increase insulin sensitivity
It's a biguanide
251
metformin SE? Contraindicated in patients with?
lactic acidosis due to lactate build up; Watch for decreased renal function, as metformin is renally excreted -> can easily exceed therapeutic index
252
metformin unintended benefit?
modest weight reduction
253
diabetes med with intracellular receptor?
thiazolidiniediones (glitazones) --> PPAR-gamma receptor regulating gene transcriptiong - increased insulin sensitivity, upregulate GLUT-4 receptor synthesis --> more glucose uptake into cells
254
glitazones SE? Exacerbates?
fluid retention, peripheral edema, weight gain;
| Exacerbate heart failure, also associated with osteoporosis
255
intestinal approach to sugar control?
acarbose and miglitol - inhibit alpha-glucosidase enzymes, so no monosaccharides to absorg --> less sugar in blood to deal with
256
kidney approach to sugar control? Where exactly? Two examples?
Block SGLT-2 in the proximal tubule --> no glucose reabsorption from filtrate; canigliflozin, dapagliflozin
257
"-flozin" suffix? SE?
SGLT-2 inhibitors; see increased incidence of UTI (candida overgrowth) and hypotension (osmotic diuresis)
258
osteoporosis drug requiring patient to sit upright for 30 minutes? Other transient SE that can be exploited?
bisphosphonates --> sit upright to avoid complications of acid reflux, esophagitis, esophageal ulcers; causes hypocalcemia, so good for treatment of acute hypercalcemia
259
bisphosphonate MoA?
Decrease osteoclast activity by binding hydroxy-apatite; when osteoclast binds the combo, it gets stuck, kind of like antimetabolite activity; also promotes osteoclast apoptosis
260
recombinant growth hormone?
somatotropin (expensive!)
261
Growth hormone levels are fine, but no growth? Tx?
Insulin-like growth factor 1 (IGF-1) deficiency; treat with mecasermin (recombinant IGF-1)
262
location of carcinoid tumor (primary, secondary)?
ileum, metastasizes to liver
263
D2 receptor agonists (2)?
cabergoline and bromocriptine
