Week 1 Flashcards
(218 cards)
1
Q
What is kinesin? Dynein?
A
A microtubule associated motor protein (ATP-powered) whose function is anterograde transport of intracellular vesicles and organelles toward the plus (rapidly growing) ends of microtubules.
In reactivation of HSV, anterograde transport of viral particles is mediated by kinesin.
During infection, dynein participates in retrograde axonal transport (i.e., moving organelles toward the nucleus). It is important in establishing latent phase following primary HSV infection by transporting viral particles to the neuronal senory ganglia.
2
Q
What does kinesin do?
A
It carries vesicles and organelles away from the cell body; toward the nerve terminal.
3
Q
What are desmosomes?
A
Protein aggregates that mediate cell-cell adhesion between epithelial cells via keratin intermediate filament interactions.
4
Q
What is the most common pathologic cause of unilateral fetal hydronephrosis?
A
A narrowing or kinking of the proximal ureter at the ureteropelvic junction (UPJ).
5
Q
What is the most common cause of bilateral fetal hydronephrosis in boys?
A
Posterior urethral valves.
6
Q
What causes posterior urethral valves?
A
An obstructive, persistent urogenital membrane at the junction of the bladder and urethra.
7
Q
What does vesicourethral reflux result from?
A
The incomplete closure at the vesicoureteral junction, which can lead to chronic dilation of the ureter and renal pelvis (unilateral or bilateral). This is a non-obstructive cause of fetal hydronephrosis.
8
Q
What are the characteristic features of the M3 variant (Acute Promyelocytic Leukemia) of Acute Myelogenous Leukemia (AML)?
A
Presence of promyelocytes (w/ Auer rods) on smear associated with disseminated intravascular coagulation (bleeding, thrombocytopenia, prolonged prothrombin and activated thromboplastin time).
Auer rods are deformed azurophilic granules found in cytoplasm and stain for myeloperoxidase, indicate myeloid differentiation.
Pathogenesis: in AML, immature cells of myeloid origin are unable to differentiate and mature. They proliferate in bone marrow and suppress the growth and multiplication of other hematopoietic precursors.
Presentation: anemia (fatigue, pallor), thrombocytopenia (petechiae, hemorrhages), neutropenia (fever, opportunistic infections) result from marrow replacement by leukemic cells
9
Q
What is the cytogenetic abnormality in AML?
A
t(15;17); it inhibits promyelocyte differentiation and triggers development of Acute ProMyeloctyic Leukemia.
10
Q
What is the treatment for AML?
A
All-trans retinoic acid.
11
Q
What are the functions of ch15 and 17 in AML?
A
15: promyelocytic leukemia gene
17: retinoic acid receptor alpha gene
Gene product inhibits differentiation of myeloblasts
12
Q
What is the chromosomal translocation in Burkitt Lymphoma?
A
t(8;14); 8-cMyc protooncogene 14-Ig heavy chain region
13
Q
What is the chromosomal translocation in Chronic Myelogenous Leukemia?
A
t(9;22); transloction of the ABL gene from 9 to 22; BCR-ABL with tyrosine kinase activity
14
Q
What is the chromosomal translocation in Mantle Cell Lymphoma?
A
t(11;14); results in activation of the cyclin D gene.
15
Q
What is the result of deletion of 13q?
A
Molecular defects are seen in Chronic Lymphocytic Leukemia.
16
Q
How does alcohol function as a disinfectant?
A
It disrupts cell membranes and denatures proteins. It does not destroy bacterial spores.
17
Q
What is sickle cell anemia?
A
Pathogenesis: Autosomal recessive; HbS; the nonpolar/neutral amino acid valine REPLACES the charged/acidic amino acid glutamate at position 6 of the beta globlin chain; result - hemoglobin molecules aggregate under anoxic conditions/deoxygenation; after polymerization, HbS forms a gel then meshwork of fibrous polymers causing the RBCs to distort into abnormal sickle shape
Sickling: due to hydrophobic interaction that cause polymerization; promoted by low O2 levels in RBC, high acidity, high 2, 3, BPG, high altitude, or low blood volume (dehydration); increased O2 unloading to tissues; pts have increased folic acid and B12 requirements due to increased RBC turnover
Presentation: African American; microvascular occlusion and microinfarcts, Anemia, jaundice, and painful swelling of the hands and feet (dactylitis (hand-foot syndrome)); abdominal pain; repeated infarcts produce spleen that is shrunken, discolored, and fibrotic (autosplenectomy - infection w/ encapsulated organisms); acute chest syndrome (vaso-occlusive crisis localized to pulmonary vasculature; precipitated by pulmonary infection)
Labs: increased indirect bilirubin and LDH, decreased haptoglobin
Dx: hemoglobin electrophoresis
Tx: hydroxyurea (increases HbF) reserved for frequent pain crises; hydration (Gardos channel blockers hinder the efflux of K and H20 from the cell, preventing dehydration of RBCs and reducing the polymerization of HbS)
18
Q
Describe pityriasis rosea.
A
Solitary pink or brown scaly plaque with central clearing on the trunk, neck, or extremities (herald patch).
19
Q
What is the classic pattern on pityriasis rosea?
A
Ovoid maculopapular rash with lesions classically oriented in an oblique direction along the skin tension lines on the back (Christmas tree pattern).
20
Q
What is the role of neutrophils in candida infection?
A
They prevent the disseminated/ HEMATOGENOUS spread of candida (disseminated candidasis) .
21
Q
What is the role of T lymphocytes in candida infection?
A
They prevent local/SUPERFICIAL candida infection (e.g., oral/esophageal candidasis, cutaneous candidasis, candida vulvovaginitis).
22
Q
What is the use of fibinolytic drugs (tPA)?
A
Treatment of acute MI. Most effective when used w/in 6h of onset of STEMI.
23
Q
What are contraindications to fibrinolytic use?
A
Hemorrhagic stroke, ischemic stroke w/in 1y, active internal bleeding, BP of more than 180/110, and suspected dissecting aneurysm.
24
Q
What is the consequence of fibrinolytic use?
A
Restoration of blood flow after clot lysis in MI can lead to arrhythmias, also referred to as reperfusion arrhythmia (accelerated idioventricular rhythm). These arrhythmias are usually benign.
25
Which enzyme does acetyl coa stimulate in the metabolism of pyruvate?
Pyruvate carboxylase.
26
What is the enzyme deficiency in Fabry's Disease?
X-linked; alpha-galactosidase A; accumulation of globotriaoslyceramide (Gb3).
27
What is the early clinical presentation of Fabry's disease?
Neuropathic pain, hypohidrosis (lack of sweating); angiokeratomas and telangiectasias.
28
What is the late clinical presentation of Fabry's disease?
Cerebrovascular (e.g., TIA, stroke), cardiac (e.g., LVH); Most common causes of death.
29
What is the result of (globotriaoslyceramide) Gb3 accumulation in the kidney?
In adulthood: (globotriaoslyceramide) Gb3 builds up in the glomerulus and distal tubule, resulting in proteinuria and polyuria; can progress to renal failure.
30
Is the liver affected in Fabry's Disease?
No.
31
What is the presentation of Pyruvate Dehydrogenase Deficiency?
Neurologic defects, lactic acidosis, increase in serum alanine starting in infancy.
32
What is treatment for pyruvate dehydrogenase deficiency?
Increased intake of ketogenic nutrients (e.g., high fat content, low carb, or increase in lysine and leucine).
33
What are the two exclusively ketogenic amino acids?
Lysine and leucine; they cannot be metabolized to pyruvate and consumption will not lead to increased production of lactic acid.
34
What is the common demographic for direct inguinal hernias?
Elderly men.
35
What are the borders of Hesselbach's triangle?
Direct inguinal hernia; inguinal ligament inferiorly, inferior epigastric vessels laterally, rectus abdominus medially, transversalis fascia forms the floor.
36
What causes a direct inguinal hernia?
Breakdown of the transversalis fascia.
37
Do direct inguinal hernias pass through the deep inguinal ring?
No, they only pass through the superficial/external inguinal ring. Therefore, they are only covered by the external spermatic fascia.
38
What is the typical presentation of right-sided colon cancers?
Present with features of **Fe deficiency anemia** (e.g., fatigue, pallor) due to occult blood loss. Nonspecific sx such as anorexia, malaise, and unintentional weight loss may also occur.
39
Is recurrent grossly bloody stool associated with right-sided colon cancer?
No. Recurrent grossly bloody stool assoc. w/ abd discomfort and low grade fever is characteristic of Ulcerative Colitis.
40
Is fever common in rectosigmoid cancer?
No. It often causes hematochezia.
41
What is the clinical presentation of left side colon cancers?
They infiltrate the intestinal wall and encircle the lumen, causing constipation and symptoms of intestinal obstruction.
42
How much K+ does Bowman's capsule reabsorb?
100%.
43
How much K+ does the proximal tubule reabsorb?
65%.
44
How much K+ does the thick ascending limb absorb?
25-30%.
45
How much K+ is secreted by principal cells?
5-100%.
46
What are the primary mediators of K+ regulation?
The principal and alpha-intercalated cells of the late distal and proximal tubule.
47
What role do the alpha intercalated cells have in K+ depletion?
They reabsorb extra K+.
48
What role do the principal cells have in condition of normal or increased K+ load?
They secrete K+.
49
Where does CN 5.2 (maxillary) exit the skull?
Foramen rotundum.
50
Where does CN 5.3 (mandibular) exit the skull?
Foramen ovale.
51
Where does CN 5.1 (ophthalmic) exit the skull?
Superior orbital fissure.
52
What does unilateral injury to CN 5.3 result in?
Unopposed action of the contralateral pterygoid muscles; leads to deviation of the mandible toward the paralyzed side on opening the mouth.
53
What does CN 5.3 innervate?
Muscles of mastication (masseter, medial and lateral pterygoids, and temporalis muscles).
54
What is the chromosomal rearrangement in non-small cell lung carcinoma?
Fusion gene between EML4 (echinoderm microtubule-associated protein-like 4) and ALK (anaplastic lymphoma kinase); this results in a constitutively active tyrosine kinase.
55
Stimulation of which nerve can improve obstructive sleep apnea?
Stimulation of CN12 causes the tongue to move forward slightly, increasing the AP diameter of the airway. Reduces the # of obstructive events during sleep.
56
Turner Syndrome and pregnancy.
Pregnancy can occasionally occur spontaneously in some patients w/ TS, but the risk of spontaneous abortion, DS, and Turner syndrome are all increased in such cases.
57
What is the difference between CMV infection in an immunocompetent vs immunocompromised host?
Immunocompromised (HIV ): CMV infection can result in severe retinitis, pneumonia, esophagitis, colitis, or hepatitis.
Immunocompetent: mononucleosis-like syndrome that is heterophile antibody (monospot) negative.
58
What is biliary atresia?
A progressive, complete or partial obstruction of extrahepatic bile ducts.
Pathogenesis: Destruction is thought to be immune-related or viral induced.
Presentation: Infants within the first two months of life. Jaundice w/in the first 2mo of life, dark urine and acholic (pale or clay colored) stools due to excessive renal excretion of bilirubin and lack of intestinal bile, respectively. Hepatomegaly due to inflammation.
Labs: Elevated direct (conjugated) bilirubin and gamma-glutamyl transferase.
Dx: Liver biopsy; reveals intrahepatic bile duct proliferation, portal tract edema, and fibrosis.
Tx: Urgent surgical intervention is required, as lack of intervention can lead to death (due to cirrhosis) usually w/in 2y.
59
What is the presentation of galactosemia?
Vomiting, diarrhea, and lethargy during the first few days of life due to inability to digest breast milk or formula.
60
Patients with profound and prolonged neutropenia are at especially high risk for what?
Viral and fungal infections.
61
What is aspergillosis?
Monomorphic, exists only in mold form (i.e., muticelluler hyphae) at acute angles
**Invasive aspergillosis:** immunosuppressed; fever, chest pain, cough, dyspnea, and hemoptysis; lung granulomas; can spread hematogenously causing infection in skin, paranasal sinuses, kidneys, endocardium, and brain
Dx: light microscopy shows V-shaped, narrow, septate hyphae
Tx: amphotericin b
**Aspergillomas:** fungal balls caused by Aspergillus; grows in pre-existing lung cavities formed by TB or bronchiectasis (represents **colonization**), shifts when the patient changes position; limited to pre-existing cavity; surgically removed
**Allergic bronchopulmonary aspergillosis**: hypersensitivity reaction in pts w/ asthma; presents w/ wheezing and migratory pulmonary infiltrates
Dx: increased serum IgE, increased titers of antibodies against Aspergillous
Tx: corticosteroids
62
What is the presentation of cat-scratch disease?
Low fever, lymphadenopathy, and a self-limited disease course.
63
What does bartonella henselae cause?
Cat-scratch disease, bacillary angiomatosis, and culture negative endocarditis.
64
What is the role of estrogen in gallstone formation in pregnant women or women using OCPs?
It upregulates hepatic HMG-CoA reductase activity, which causes the bile to become supersaturated with cholesterol.
65
What is the role of progesterone in gallstone formation in pregnant women or women using OCPs?
It reduces bile secretion and slows gallbladder emptying; hypomotile.
66
What test should be performed before initiating therapy with metformin?
Serum creatinine measurement because the buildup of lactic acid is toxic to the kidney.
67
In addition to the hypothalamus, where else is somatostatin secreted from?
Delta cells of the pancreas.
68
What does somatostatin from the delta cells do?
It **decreases** the secretion of secretin, cholecystokinin, glucagon, insulin, and gastrin.
69
What is the presentation of somatostatinomas?
Hyperglycemia or hypoglycemia, **steatorrhea** (excessive fat in the feces), and **gall** **bladder** stones.
70
Why do gallbladder stones form in somatostatinomas?
Poor gallbladder contractility, which is secondary to inhibition of cholecystokinin release.
71
What are PFTs in COPD?
FEV1 is decreased more than FVC.
72
Which primary cell lines are increased in stable COPD?
Neutrophils, macrophages, and CD8 t cells.
73
What are the roles of neutrophils, macrophages, and CD8 t cells in COPD?
They release enzymes and **proteases** such as neutrophil **elastase** that cause alveolar damage, reduced ciliary motion, and increased mucus secretion by goblet cells. Impaired ability to phagocytize bacterial pathogens.
74
Describe the role of Bowman's capsule and the proximal tubule regarding the concentration of para-aminohippuric acid (PAH) in the kidney.
**Some** PAH is freely filtered by the glomerulus into Bowman's space; however, the **majority** is **secreted** by the **_proximal tubule_** via carrier-mediated active transport.
75
Is PAH reabsorbed by any portion of the nephron?
No.
76
Does the liver eliminate highly lipophilic drugs well?
Yes. Drugs w/ high intrinsic hepatic clearance tend to have high **lipophilicity** and a **high** volume of distribution.
77
How well are highly lipophilic drugs eliminated by the kidney?
They are poorly eliminated by the kidney as they rapidly cross tubular cell membranes after filtration to **re-enter tissues**.
78
In addition to the liver, what other areas can highly lipophilic drugs access?
Brain and adipose tissue.
79
What are two treatments for drug-induced Parkinson Disease?
Trihexyphenidyl and benztropine.
80
What is a common complication of cystic fibrosis?
A history of recurrent respiratory infections caused by P. aeruginosa, chronic diarrhea, and failure to thrive.
81
What are GI complications of cystic fibrosis?
**Steatorrhea** and **failure** to thrive are due to **malabsorption** due to obstructive fibrosis and progressive insufficiency of the **exocrine pancreas**. Fat soluble vitamin **deficiencies** (ADEK).
82
What is one treatment option for cystic fibrosis pertaining to GI issues?
Pancreatic **lipase** supplementation to enhance macronutrient and vitamin absorption.
83
What do gap junctions consist of and what is their function?
Connexin proteins; intercellular communication.
84
What do tight junctions consist of and what is their function?
Claudins, occludin; paracellular barrier.
85
What do adherens junctions consist of and what is their function?
Cadherins; cellular anchor.
86
What do desmosomes consist of and what is their function?
Cadherins (e.g., desmogleins, desmoplakin); cellular anchor.
87
What do hemidesmosomes consist of and what is their function?
Integrins; cellular anchor via keratin intermediate filaments.
88
How does estrogen affect cell junctions prior to delivery?
Stimulates upregulation of gap junctions between myometrial smooth muscle cells.
89
What is the effect of estrogen on oxytocin receptors prior to delivery?
It increases expression of uterotonic (e.g., oxytocin) receptors, which mediate Ca2+ transport through ligand-activated calcium channels.
90
Where does the psoas muscle originate?
From the anterior surface of the transverse processes and lateral surface of the vertebral bodies at T12-L5.
91
What is the function of the psoas muscle?
It acts primarily to flex the thigh at the hip and also contributes somewhat to lateral rotation and abduction of the thigh.
92
What is the presentation of acute salicylate intoxication?
N/v, confusion, **dizziness**, **tinnitus**, fever, and tachypnea w/in several hours after ingestion.
93
Which acid-base abnormalities are characteristic in acute salicylate intoxication?
Respiratory alkalosis and anion gap metabolic acidosis.
pH will be in the normal range.
94
What is the appearance of pulmonary edema?
**Bilateral** fluffy-appearing **infiltrates**, not unilateral lung opacification.
95
What is the appearance of interstitial lung disease?
**Reticular** markings in **both** lungs on CXR rather than complete opacification.
96
What is the appearance of air accumulation (pneumothorax)?
Increased **lucency** on the affected side. Tension pneumo will cause tracheal deviation away from affected lung.
97
What is the appearance of pleural effusion?
Complete hemithorax **opacification**. Causes tracheal deviation **away** from affected lung.
98
What is the appearance of atelectasis?
Unilateral pulmonary **opacification** and deviation of the mediastinum **toward** the **opacified** lung.
99
What is the presentation of ovarian cancer?
Abdominal **distension**, **ascites**, **pleural** **effusion**, bowel obstruction, decreased appetite, weight loss, and an ovarian mass.
100
What are risk factors for **ovarian** cancer?
BRCA mutations, **repeated** ovulation, **nulliparity**, or ovarian dysfunction (**infertility**).
101
What are protective factors for ovarian cancer?
Oral contraceptives, multiparity, and breastfeeding. **Less** **repair** at the ovarian surface due to **reduced** lifetime ovulation frequency.
102
What is recombination?
**Gene** **exchange** that occurs through the crossing over of 2 dsDNA molecules.
103
What is transformation?
**Uptake** of **naked** DNA by a prokaryotic or eukaryotic cell; incorporation of viral DNA into a host cell chromosome (lysogeny).
104
Does transformation cause genomic change in progeny virions?
No.
105
Which cells display MHCII?
**_Only_** antigen presenting cells.
106
Which cells display MHC I?
Most nucleated cells of the human body.
107
What do MHC I present?
Self antigen, tumor antigen, or antigen synthesized by the cell due to viral infection of that cell.
108
What do MHC II present?
Exogenous antigen.
109
How are antigens presented by MHC II loaded?
Antigen is phagocytosed or endocytosed and loaded onto MHC II within **acidified** **endosome**.
110
Is PCOS a risk factor for DM2?
Yes, due to increased insulin resistance.
111
What are the characteristics of PCOS?
Hyperandrogenism, irregular periods, and/or polycystic ovaries on ultrasound.
112
PCOS patients are at the greatest risk for developing what? Treatment?
Endometrial carcinoma.
**Pregnancy desired:** **clomiphene**; selective estrogen receptor modulator that decreases negative feedback inhibition on hypothalamus by circulating, thereby **increasing** **gonadotropin** **production**
**Pregnancy not desired**: **E-P oral contraceptive pills** to minimize **endometrial** **proliferation**, reduce androgen symptoms (e.g., hirsutism, acne) and **prevent** unwanted pregnancy
113
How does dry beri beri present in a 78yo man?
Symmetrical **peripheral** **neuropathy** of the distal extremities, with resulting **sensory** and **motor** impairments.
114
How does wet beri beri present in a 78yo man?
Dry beri beri plus the **addition** of **cardiac** involvement (cardiomyopathy, high-output congestive heart failure, peripheral edema, and tachycardia).
115
What are the symptoms of Wernicke-Korsakoff syndrome?
Confusion, ataxia, oculomotor abnormalities, and permanent memory deficits.
116
What is precision?
**Reliability**. The ability of a test to **reproduce** identical or similar results w/**repeated** measurements.
117
What is accuracy?
**Validity**. The ability of a test to measure what it is supposed to measure.
118
When is reliability maximal?
When random error is **minimal**.
119
What is the main presenting symptom in a 73yo man with **bladder** **cancer**?
**Painless** hematuria.
120
What kind of cells are a majority of bladder carcinomas?
Urothelial (transitional cell) carcinomas.
121
What is the major determinant of prognosis of bladder cancer?
Tumor **penetration** of the bladder wall.
122
Describe the cystic fibrosis transmembrane conductance regulator (CFTR) protein.
It is a transmembrane **_ATP_**-**_gated_** **chloride** channel.
123
In what setting can hyperosmotic volume contraction occur?
Diabetes insipidus, decreased fluid intake (**dehydration**), and with profuse sweating (due to the **hypotonic** nature of sweat).
124
What is the presentation of paroxysmal supraventricular tachycardia in a 32yo male?
**Sudden** onset heart **palpitations**; HR\>160/min.
125
What is treatment for paroxysmal supraventricular tachycardia?
**Valsalva** or **carotid** sinus massage.
126
How do valsalva or carotid sinus massage work?
They increase **vagal** **tone** to increase the **refractory** period in the AV node and help **prevent** a **reentrant** circuit from conducting.
127
What can be used if valsalva fails?
IV **adenosine**.
128
What muscles are involved in the valsalva?
The **rectus** **muscles**. They increase **intraabdominal** and **intrathoracic** pressure.
129
What is the drainage sequence of **internal** hemorrhoids?
Arteries: **Superior** rectal artery (branch of IMA)
Veins: Superior rectal vein\>IMA\>splenic vein\>portal vein.
Cancers arising in **proximal rectum** metastasize to the **liver** first due to **hematogenous** dissemination through the **portal system**.
Lymphatics: drains to **internal** iliac LN; covered by **columnar** epithelium; **visceral** innervation (**not** **painful**)
130
What is the drainage sequence of external hemorrhoids?
Arteries: **Inferior** rectal artery (branch of **internal** pudendal artery)
Veins: Inferior **rectal** vein\>internal **pudendal** vein\>internal **iliac** vein\>**common** iliac vein\>**IVC**
Cancers of the distal rectum and anus metastasize to the **lungs** because the middle and inferior rectal veins drain into the **caval system**.
Lymphatics: drain to **superficial** **inguinal** LN; **somatic** innervation (inferior rectal nerve, branch of pudendal; **painful**) ; covered by modified **squamous** epithelium
131
How do you treat hemorrhoids?
**Rubber** **band** **ligation** to cut off their blood supply, causing them to **degenerate**.
132
Describe the Huntington gene mutation.
**Gain of function** mutation that increases histone **deacetylation**. **Silences** genes necessary for **neuronal** **survival**.
133
What is the result of loss of the Huntington gene?
Embryonic death.
134
What is the MOA of fidaxomicin in treating C. diff?
Oral, **macrocyclic** antibiotic;
Inhibits the **sigma** subunit of **RNA** **polymerase**;
Leads to protein synthesis **impairment** & cell death (**bactericidal**).
135
What is the presentation of hypovolemic shock?
Hypotension, **tachycardia**, and **cool** extremities.
136
Describe TPR and myocardial contraction in hypovolemic shock.
They are already high due to **sympathetic** activation.
137
How do you treat hypovolemic shock?
IV **fluids** increase the **intravascular** and **LVEDV**.
138
What is the effect of increased preload after IV fluids are administered to treat hypovolemic shock?
The increase in preload stretches the myocardium and increases the end-diastolic sarcomere length, leading to an increase in **SV** and **CO** by the Frank Starling mechanism.
139
What is the MOA of statins?
They competitively inhibit HMG CoA **reductase** (involved in synthesis of **cholesterol**).
140
What is the MOA of bile acid-binding resins?
Bind bile acids in the GI tract and increase their **excretion**. Results in **decreased** hepatic cholesterol because **synthesis** of new bile acids **consumes** **liver cholesterol stores**.
141
What does etanercept do?
**TNF alpha inhibitor** added to methotrexate to treat moderate to severe rheumatoid arthritis.
It is a fusion protein linking a soluble **TNF alpha receptor** to the Fc component of human IgG1.
It reduces the biological activity of TNF alpha by **acting as a decoy receptor.**
142
What is the presentation of classic galactosemia?
Jaundice, vomiting, and hepatomegaly.
143
What enzyme deficiency causes classic galactosemia?
Autosomal Recessive; galactose-1-phosphate uridyl transferase.
144
What is sulfamethoxazole?
Structural **analogue** of **PABA** that inhibits **dihydropteroate** **synthetase** (enzyme needed for dihydrofolic acid synthesis).
145
What are the physical signs of stimulant intoxication?
Tachycardia, HTN, hyperthermia, diaphoresis, and mydriasis.
146
What is the classic triad for the presentation of ataxia-telangiectasia?
Autosomal Recessive; Cerebellar **Ataxia**, spider **Angiomas**, **IgA** deficiency (risk of sinopulmonary infection).
147
What is poststrep glomerulonephritis?
Most common cause of acute pediatric glomerulonephritis;
Presentation: Facial and periorbital edema, moderate HTN in patient with **hematuria** is a nephritic syndrome (tea/**cola**-colored urine). Occurs 2-4 weeks after strep infection of **pharynx** or **skin** (impetigo).
Light microscope: glomeruli are enlarged and **hypercellular;** **immune complexes** are seen as electron dense deposits on epithelial side of basement membrane
IF: "**Starry** **sky**": **granular** appearance "**lumpy** **bumpy**" appearance, subepithelial **humps**; deposition of IgG, IgM, and C3b along GBM and mesangium.
Labs: urinalysis (+**protein**, **blood**, +/- RBC casts);
serum - **decreased C3**; increase serum creatinine, anti-DNas B and AHase, ASO and anti NAD (from preceding pharyngitis); cryoglobulins; **C4** is **_NORMAL_**
Poor prognostic factor: **increased age**
148
What is Familial Dysbetalipoproteinemia (type III)?
Pathogenesis: Autosomal Recessive; defective **_ApoE3 and E4._**
Presentation: **Premature** **coronary** artery disease and **peripheral** vascular disease; Tuboeruptive and palmar **xanthomas**
Elevated: **Cholesterol** and **TG**; high blood level of **chylomicrons** and **VLDL**
149
What enzyme converts acetyl coa to malonyl coa?
_**Acetyl** **coa** **carboxylase**_; needs **B7**; fatty acid **synthesis**
150
What enzyme converts propionyl coa to methylmalonyl coa?
**Propionyl coa carboxylase**; needs B7; fatty acid **oxidation**
151
In central venous catheters, which vein has a high risk of infection?
**Femoral** **vein**.
152
What microscopic change will you see 12-24h after an ischemic stroke?
"**Red** **neurons**" (**eosinophilic** cytoplasm, **pyknotic** nuclei, **loss** of Nissl substance).
153
What microscopic change will you see 24-72h after an ischemic stroke?
**Necrosis** + **neutrophils**.
154
What microscopic change will you see 3-7d after an ischemic stroke?
Mac/microglial infiltration and phagocytosis begin.
155
What microscopic change will you see 1-2w after an ischemic stroke?
**Reactive** gliosis; **vascular** proliferation around the necrotic area.
156
What macroscopic change will you see 1-2 weeks after an ischemic stroke?
**Liquefactive** necrosis (1w -1mo).
157
What microscopic change will you see \>2w after an ischemic stroke?
**Glial** **scar** formation.
158
What macroscopic change will you see \>2w after an ischemic stroke?
**Cystic** area surrounded by dense **glial** **fibers** (\>1 month).
159
What are symptoms of a carnitine deficiency?
Muscles and Sugar:
Muscle **weakness**, **elevated** muscle **triglycerides**, **hypotonia**; **Hypoketotic** **hypoglycemia**.
160
What is medium chain acyl coa dehydrogenase (MCAD) deficiency?
Pathogenesis: autosomal recessive; inability to degrade medium-length fatty acids by beta **oxidation**; lack of acetyl coa **impairs** **ketogenesis** and **gluconeogenesis**; deficiency in **acyl coA dehydrogenase**
Presentation: follows a period of fasting or increased metabolic stress;
Sickness and sugar: Vomiting, lethargy, liver dysfunction (fat accumulation causes hepatomegaly), hyperammonemia, seizure, coma;
**Hypoglycemia**, **hypoketotic** hypoglcyemia.
Tx: prevention of catabolism by avoiding prolonged fasting as well as promptly supplying **glucose** during periods of illness
161
What is the most commonly deficient enzyme in impaired beta oxidation?
**Acyl coa dehydrogenase**.
162
What is the presentation of diffuse esophageal spasm?
**Disorganized** non-peristaltic contractions--\>solid/liquid dsyphagia, **chest** **pain**.
163
What is the pathogenesis of diffuse esophageal spasm?
**Impaired** **inhibitory** neurotransmission w/in esophageal **myenteric** plexus. So, it keeps firing.
164
What is the etiology of urge incontinence?
Detrusor **hyperactivity**.
**Sudden**, **overwhelming** urge to urinate.
165
What is the etiology of stress incontinence?
**Decreased** urethral sphincter tone; urethral **hypermobility**.
Sx: Leakage with increased abdominal **pressure**; **coughing**, **lifting**, **sneezing or vigorous effort** - diagnostic of stress incontinence
166
What is the etiology of overflow incontinence?
**Impaired** detrusor **contractility**; bladder outlet **obstruction**.
Sx: **Incomplete** emptying & persistent **involuntary** **dribbling**.
167
At what blood sugar level does osmotic diuresis occur?
\>250mg/dL
168
What are the two s-100 postive tumors and what is their cell of origin?
Melanoma and schwannoma; neural crest cell origin
169
What enzyme is needed to convert BH2 to BH4, the cofactor for **phenylalanine hydroxylase** and **tyrosine hydroxylase**?
Dihydropteridine reductase.
170
What are the cyp450 **inducers** (+, **_promote_** drug metabolism)?
Barbituates
Cabamazepine
Chronic alcohol
Cyclophosphamide
Griseofulvin
Modafinil
Nevirapine
Phenytoin
Rifampin
St. John's Wort
Most chronic alcoholics steal phen-phen and never refuse greasy carbs.
171
What are the cyp450 inhibitors?
Acute alcohol abuse
Amiodarone
Azoles
Cimetidine
Clarithromycin
Chloramphenicol
Erythromycin
Fluroquinolones
Grapefruit juice
Isoniazid
Metronidazole
Omeprazole
Sodium valproate
Sulfonamides
Ritonavir (protease inhibitors)
172
What are the substrates of cyp450?
Anti-epilectics
Metronidazole
OCPs
Theophylline
Warfarin
173
What is hereditary fructose intolerance? What is essential fructosuria?
Pathogenesis: Autosomal Recessive; deficiency in **Aldose B (bad)**, which impairs **gluconeogenesis**
Presentation: present when fructose-containing foods are introduced into diet (fruits, vegetables, honey, table sugar); vomiting, hypoglycemia about 20-30m after fructose ingestion; **failure to thrive**, **hepatomegaly**, and **jaundice**
Undiagnosed pts may eventualy develop liver and renal failure
Tx: **elimination** of dietary fructose
[**Fructokinase** **deficiency** causes **essential** **fructosuria**, a **benign** autosomal recessive disorder. Fructose from diet is absorbed and secreted freely in urine due to impairment of 1st step in fructose metabolism]
174
What are consequences of hypoglycemia?
Lethargy, sweating, vomiting, and dehydration.
175
What is the enzyme deficiency and accumulated substrate in Fabry disease?
XLR; alpha galactosidase A; globotriaoslyceramide/ceramide trihexoside.
176
What are key features of Fabry disease?
Angiokeratomas, peripheral neuropathy, glomerulopathy.
177
What is the enzyme deficiency in Tay-Sachs and the accumulated substrate?
AR; Ashkenazi Jews
Beta-hexosaminidase A; GM2 (ganglioside).
178
What are the key features of Tay Sachs?
Macular cherry-red spot; progressive neurodegeneration.
179
What is Gaucher Disease?
AR; Ashkenazi Jews; Deficiency in Beta-glucocerebrosidase; accumulated substrate: glucocerebroside, glycolipid component of WBC and RBC membranes.
Presentation: **Bone pain/osteopenia** due to BM invasion/inflammation; easy bleeding and bruising, pallor and fatigue due to **pancytopenia**; abdominal distension due to **hepatosplenomegaly**.
Histology: lipid-laden macrophages (or Gaucher cells) look like "wrinkled tissue paper", "wrinkled silk" or **"crumpled newspaper"**
180
What is the enzyme deficiency and accumulated substrate in Niemman-Pick?
AR; Ashkenazi Jews
## Footnote
Sphingomyelinase; sphingomyelin.
181
What are the key features of Niemann-Pick?
Macular cherry-red spot; progressive neurodegeneration; hepatosplenomegaly.
182
What is the enzyme deficiency and accumulated substrate in Krabbe?
AR; galactocerebrosidase; galactocerebroside and psychosine.
183
What are the key features of Krabbe?
Progressive neurodegeneration; optic atrophy, peripheral neuropathy.
184
What is the enzyme deficiency in metachromatic leukodystrophy?
AR; arylsulfatase A; cerebroside sulfate.
185
What are the key features of metachromatic leukodystrophy?
Progressive neurodegeneration; peripheral neuropathy.
186
What is the origin of Renal Cell Carcinoma?
Epithelial cells of the Proximal Renal Tubules/Proximal Convoluted Tubule of the kidney.
187
What is theophyline? What is the major cause of morbidity and mortality in theophylline intoxication?
Theophylline is an **adenosine receptor antagonist, phosphodiesterase inhibitor,** and **indirect adrenergic agent**; narrow therapeutic index; metabolized by cyp450 enzymes; causes bronchodilation
Inhibition of cyp450 by concurrent illness (e.g., infection w/ fever) or drugs (e.g., **cimetidine, cipro, macrolides, verapimil**) can raise serum concentration and cause toxicity;
Toxicity: **Seizures** (**tachyarrhythmias** are the other major concern; do not cause QT prolongation).
188
What is the presentation of Patau Syndrome?
Trisomy 13: intellectual disability, cutis aplasia, microcephaly/holoprosencephaly, microphthalmia, **cleft** **lip**/**palate**, congenital heart disease, umbilical hernia/omphalocele, polycystic kidney disease, polydactyly.
189
What is the presentation of Edwards Syndrome?
Trisomy 18: **Prominent** **occiput**, intellectual disability, **clenched** **fists** (w/ **overlapping** fingers), low set ears, micrognathia, **rocker****bottom****feet**, congenital heart disease.
190
What are the common causes of meningitis in newborns (0-60mo)?
Group B strep
E. coli
Listeria
191
What are the most common causes of meningitis in children (6mo-6y)?
S. pneumo
H influenza (type B)
Enterovirus
N. meningitidis
192
What are the most common causes of meningitis in people ages 6-60y?
S. pneumo
N. meningitidis (#1 in teens!; 2nd in adults)
Enterovirus
HSV
193
What are the most common causes of menginitis in people aged 60y+?
S. pneumo
Gram - rods
Listeria
194
What is the triad for paroxysmal nocturnal hemoglobinuria?
Pancytopenia
Hemolytic anemia
Venous thrombosis
195
What does ezetimibe do?
It blocks intestinal cholesterol **absorption**, decreasing liver cholesterol stores and reducing biliary cholesterol content.
196
What does gemfibrozil do?
It inhibits cholesterol 7 **alpha** **hydroxylase**; reduces cholesterol solubility and promotes gallstone formation by reducing **bile acid synthesis**.
197
What is the common clinical presentation of vit E deficiency?
**Hemolytic anemia**
**Posterior column demyelination** (loss of propioception & vibratory sense)
**Spinocerebellar tract demyelination** (ataxia)
**Peripheral nerve dysfunction** (**hyporeflexia**)
198
What is the Hawthorne effect (observer effect)?
Participants change behavior upon **awareness** of being observed.
199
What is the Pygmalion effect?
A researcher's belief in the efficacy of a treatment **changes** the outcome of that treatment;
**Higher** **expectations** lead to an **increase** in performance.
200
What does cholecystokinin do?
It is responsible for gallbladder **contraction**. It is made in the I cells of the duodenum and jejunum in response to **fatty acids and amino acids**.
201
What does somatostain do?
Secreted by **D cells** of the pancreatic islets and GI mucosa;
It inhibits the release of GH, TSH, and **suppresses** release of gastrin, CCK, VIP, secretin, insulin, and glucagon.
202
What are the symptoms of a mitochondrial encephalomyopathy?
Myopathy (red **ragged** fibers), **lactic** **acidosis**, and **neuromuscular** lesions.
203
What is restless leg syndrome?
Uncomfortable **urge** to move legs.
204
What are the clinical features of restless leg syndrome?
Unpleasant sensation in legs
Onset w/ inactivity of at night
Relief with movement
205
What are the causes of restless leg syndrome?
Idiopathic
**Iron** **deficiency**
**Uremia**
**Diabetes** (especially with neuropathy)
206
What is the treatment for restless leg syndrome?
**Dopamine** **agonists** (**pramipexole**)
Avoidance of aggravating factors (alcohol, sleep deprivation)
207
Describe Factor 8 deficieny (hemophilia A).
**X-linked recessive** coagulation disorder than can manifest as early as birth;
Easy bruising, hemarthrosis, and prolonged bleeding after surgery (tooth extraction).
208
What is delirium?
An acute-onset "confusional state" characterized primarily by waxing and waning mental status changes and impaired attention.
209
What is the drug of choice to treat deliriuim?
Low dose antipsychotics (e.g., **haloperidol**).
210
What is the 1st line treatment for acute gouty arthritis?
Nonsteroidal anti-inflammatory drugs (e.g., **aspirin**);
Inhibit COX enzymes--\>decrease prostaglandin synthesis and exert broad anti-inflammatory effect including **inhibition** of **neutrophils**.
211
What is the treatment for chronic gout?
**Uricosuric** **agents** (**probenicid**) or XO inhibitors are used to **prevent** acute attacks in patients with recurrent and progressive gouty arthritis and macroscopic tophi.
Should not be used to treat acute gout attack because they can **exacerbate** acute arthritis.
212
What is renal agenesis associated with in utero?
Severe **oligogydramnios** (too little amniotic flluid). Leads to **pulmonary** **hypoplasia**.
213
What does the Candida extract test do?
It tests **T cell immune function**.
214
What are examples of delayed-type hypersensitivity reactions?
Contact dermatitis
**Granulomatous** inflammation
Tuberculin skin test
**Candida** extract skin reaction
215
What is the inheritance pattern of G6PD deficiency and what does it cause?
**X linked recessive**; acute **hemolytic** anemia in response to **oxidant** drugs (e.g, antimalarials).
Histology: RBCs w/ **Heinz bodies**, dark, intracellular inclusions that stain with **supravital stain**; represent hemoglobin that has denatured/precipitated from oxidative stress
Labs: anemia, reticulocytosis, indirect hyperbilirubinemia, low haptoglobin
216
What is bacterial vaginosis?
Pathogenesis: **Gardnerella** vaginalis
Presentation: Thin, **_off white/grayish-white_** discharge w/ **_fishy_** odor; **No** **inflammation**; itchy
Labs: ph\>4.5 (**basic**); **Clue** cells w/ multiple gardnerella organisms (epithelial cells covered w/ gram **variable** rods); Positive **whiff** test (amine odor with **KOH** (potassium hydroxide)).
Tx: **Metronidazole** or **clindamycin**; tx of male partners **not** **recommended** as men are asymptomatic
217
What is trichomoniasis?
Pathogenesis: Trichomonas vaginalis
Presentation: Thin, yellow-green, malodorous, frothy discharge; vaginal **inflammation**.
Labs: ph\>4.5 (**basic**); Motile trichomonads (**pear**-shaped).
Dx test: **saline** **microscopy** (e.g., **wet mount**) of the discharge is the best diagnostic test for identifying trichomonads.
218
What is Candida vaginitis?
Pathogenesis: Candida albicans
Presentation: Thick "**cottage** **cheese**" discharge; vaginal **inflammation**.
Labs: **Normal** pH (3.8-4.5); **Pseudohyphae**.
Tx: Fluconazole
