Week 2 Flashcards
(181 cards)
1
Q
What are always involved in Hirschsprung disease?
A
100% of the time: rectum and anus;
75% of the time: sigmoid colon.
Squirt sign: positive; explosive expulsion of feces
2
Q
What are the 5A’s of Down Syndrome?
A
Advanced maternal age
Atresia (duodenal)
Atrioventricular septal defect (endocardial cushion defects)
Alzheimer disease (early onset)
Acute Lymphoblastic Leukemia/Acute Myelogenous Leukemia
Serum markers:
Low - maternal serum alpha fetoprotein and estriol;
High - Beta-hCG and inhibin A
Inheritance pattern: meiotic non-disjunction (95%; extra copy of ch21); unbalanced Robertsonian translocation (all or part of additonal ch21 attached to another ch); mosaicism: some (not all) cells have an extra copy of ch21; due to nondisjunction event in mitosis
3
Q
What is alpha fetoprotein?
A
It is synthesized by the fetal liver, GI tract, and yok sack. Levels increase with gestational age.
4
Q
When is maternal serum alpha fetoprotein increased?
A
Multiple gestation
Open neural tube defects (anencephaly, open spina bifida)
Ventral wall defects (e.g., omphalocele, gastroschisis)
5
Q
When is maternal serum alpa fetoprotein decreased?
A
Aneuploidies (e.g., trisomy 18 and 21).
6
Q
What is von Willebrand Disease?
A
Autosomal Dominant; absence of von Willebrand factor leads to impaired platelet function (prolong bleeding time) and coagulation pathway abnormalities due to decreased factor 8 activity (prolonged PTT)
Presentation: life long history of mucosal bleeding (gingival bleeding, epistaxis, and/or menorrhagia); increased bruisability; mucosal bleeding; prolonged bleeding during dental procedures and heavy menstrual periods; frequent nose bleeds as a child
Labs: normal platelets, PT, aPTT (can be increased), platelet count; increased bleeding time due to impaired platelet function;
Tx: desmopressin - increases vWF release from endothelial cells; also raises factor 8 levels and is used for treatment of mild hemophilia A (X-linked); minimal effect on V1 vasopressin receptor
7
Q
What is the treatment for venous thromboembolism during pregnancy?
A
Low molecular weight heparin (e.g., enoxaparin).
8
Q
Describe the latissimus dorsi.
A
Innervated by the thoracodorsal nerve;
Origin: iliac crest and lumbar fascia to the spinous processes of T7-12 and lower ribs;
Insertion: bicipital groove of the humerus;
Functions: extension, adduction, and medial rotation of the humerus.
9
Q
What are the complications of an MI 0-24h later?
A
Right ventricular failure:
Hypotension and clear lungs, Kussmaul sign;
Ventricular arrhythmia, HF, cardiogenic shock.
10
Q
What are the complications of an MI 3-5 days later?
A
- Papillary muscle rupture:
Acute, severe pulmonary edema;
severe mitral regurgitaton with flail leaflet.
- Interventricular septum rupture/defect:
New holosystolic murmur;
Stepped up O2 level between RA and RV.
11
Q
What are the complications of acute MI 5-14d later?
A
Free wall rupture:
hemopericardium and pericardial tamponade;
profound hypotension and shock;
JVD distension;
Distant heart sounds.
12
Q
What is the most frequent complication of fibrinolytic therapy?
A
Bleeding.
13
Q
What is the MOA of arepitant and fosaprepitant; what is their clinical use?
A
MOA: Neurokinin 1 (NK1) receptor antagonists - they prevent substance P release);
Use: Chemotherapy-induced emesis.
14
Q
What does motilin do?
A
It regulates interdigestive migrating contractions;
Erythromycin is a motilin receptor agonist used for gastroparesis.
15
Q
What is neuropeptide Y?
A
NT found in CNS; plays a role in appetite and pain perception.
16
Q
What are symptoms of arginase deficiency?
A
Spastic diplegia
Abnormal movements
Growth delay in setting of elevated arginine levels
Mild or no hyperammonemia
Tx: Low protine diet devoid of arginine.
17
Q
What are two dopamine agonist that direct stimulate dopamine receptors?
A
Bromocriptine (ergo compound);
Pramipexole and ropinirole (non-ergot compounds).
18
Q
What does amantidine do (in the setting of Parkinson’s)?
A
Indirect and direct dopaminergic agent;
Alleviates motor sx of PD by enhancing effects of endogenous dopamine.
Has anticholinergic properties to reduce tremors.
19
Q
What are the central adverse effects of dopamine?
A
Anxiety and agitation;
Caused by L-dopa, regardless of whether carbidopa is added to levodopa treatment.
20
Q
How do acute phase reactants impact RBCs?
A
Fibrinogen and globulins cause RBC to form rouleaux formation which increases ESR.
21
Q
What are left-sided frontal lobe lesions associated with?
A
Apathy and depression.
22
Q
What are right-sided frontal lobe lesions associated with?
A
Disinhibited behavior.
23
Q
How does treatment that prolongs survival impact prevalence?
A
Any treatment that prolongs survival, but does not cure the disease will increase prevalence due to an increase in the number of afflicted (but still living) individuals over time.
24
Q
What is the Kozak consensus sequence?
A
(Gcc)GccRccAUGG; occurs on eukaryotic mRNA,
R is either Adenine (A) or Guanine (G);
Purine A or G is positioned 3 bases upstream from AUG in the initiation process.
This sequence helps initiate translation at the methionine start codon (AUG).
25
What is the etiology of Severe Combined Immunodeficiency?
Pathogenesis**: Defective IL2R gamma** (X-linked recessive); **adenosine deaminase deficiency** (autosomal recessive); Leads to **failure** of T cell development; B cell **dysfunction** due to absent T cell.
Presentation: Recurrent, severe viral, fungal, or opportunistic (i.e., Pneumocystis) infections; Chronic diarrhea; Failure to thrive.
Tx: Stem cell transplant.
26
What does the endoderm give rise to?
Structures derived from the i**nner lining of the primitive gut tube**:
eustachian tube, thymus, thyroid follicular cells; epithelial surfaces of the trachea, bronchi, lungs, liver, biliary tree; pancreas, GI and bladder epithelium; anal canal **above** the **pectinate** **line**, most of urethra and **lower** vagina (dervied from urogenital sinus),
27
What does the mesoderm give rise to?
**Dermis** as well as bones, muscles, blood vessels, and visceral tissue
**Serous** **lining** of body cavities (peritoneum, pericardium, pleura)
**Spleen** (derived from **foregut** mesentery)
Cardiovascular structures, lymphatics, wall of gut tube, **upper** **vagina**, **kidneys**, adrenal **cortex**, **testes**, **ovaries**
28
What doe the neural tube give rise to?
**Brain** (**posterior** pituitary CNS neurons, oligodendrocytes, dendrocytes, astrocytes, ependymal cells, pineal gland), retina, spinal cord
29
What does the surface ectoderm give rise to?
**Epidermis**;
**adenohypophysis** (anterior pituitary), lens of the eye, epithelial linings or oral caviatyi, sensory organs of ear, olfactory epithelium, mammary glands (modified sweat glands), anal canal **below** pectinate line
30
Which tumors metastasize to the brain commonly?
Lung cancer;
Renal cancer;
Melanoma.
31
Why is the macula spared in homonymous hemianopia?
The macula is spared because collateral blood is supplied by the middle cerebral artery to the occipital lobe.
32
What muscle is paralyzed in an interscalene nerve block?
Diaphragm due to anesthesis of the phrenic nerve root (C3-C5) as they pass through the interscalene sheath.
33
What are characteristic findings of Primary Biliary Cholangitis?
Pathogenesis: autoimmune; destruction of small bile ducts in the liver
Presentation: **pruritus** (due to bile acid accumulation in the skin), fat soluble vitamin deficiencies; jaundice later in course of disease
Histology: Lymphocytic infiltrate; Granulomas.
Labs: Anti-mitochondrial antibody;
Classically seen in middle-aged women with **hx of autoimmune disease**.
34
What is the Jarisch-Herxheimer reaction?
An acute inflammatory reaction occuring hours after treatment for spirochetal (e.g., syphilis) infections. Rapid lysis oif spirochetes releases inflammatory bacterial lipoproteins into circulation and causes acute feveres, rigors, and myalgias.
35
Describe bronchiolitis.
Etiology: respiratory syncytial virus; age less than 2yo
Presentation: low-grade fever, cough, hypoxemia, tachypnea, increased work of breahting, retracts w/ diffuse **wheezes and crackles.**
36
What does marked unilateral kidney atrophy suggest?
Renal artery stenosis.
Due to atherosclerotic changes from HTN, smoking;
Fibromuscular dysplasia in women of childbearing age;
HTN and an abdominal bruit are often present.
37
Describe advance directives.
It takes precedence over the wishes of family members. Physicians should respect patient autonomy and adhere to patients' wishes as outlined in advance directives.
38
What is aplastic anemia?
Pathogenesis: most cases are acquired from a direct toxic insult or T cell-response leading to apoptosis of pluripotent stem cell; unknown etiology in most children
Presentation: Result of **pancytopenia** - **anemia** (fatigue, weakness, pallor), **thrombocytopenia** (mucosal bleeding, easy bruising, petechiae), **leukopenia** (recurrent infections); **no splenomegaly** due to lack of available hematopoietic progenitor cells and therefore lack of extramedullary hematopoiesis
Dx: biopsy showing **hypocellular** bone marrow composed mainly of **fat and stromal cells**.
39
What causes polycythemia vera and what is the presentation?
Pathogenesis: Mutation where valine is replaced with phenylalanine (V617F) involving JAK2, a non-receptor (cytoplasmic) tyrosine kinase associated with the erythropoietin receptor; mutation makes stem cells **more** **sensitive** to growth factors such as **EPO** and **thrombopoietin**
Presentation: aquagenic pruritus, facial plethora (reddish complexion), and splenomegaly.
Labs: increased erthyrocyte mass, increased plasma volume, thromocytosis, leukocytosis, and **low** **EPO** levels.
40
What is the function of the nucleolus?
It functions as the primary site of ribosome synthesis and assembly.
All ribosomal RNA except 5S rRNA is transcribed in the nucleolus.
41
Describe the hormone receptor for epinephrine, norepinephrine and glucagon?
Membrane bound G protein coupled receptor that activates adenyl cyclases and increases cAMP.
42
ST elevation in which leads indicate an MI in the left circumflex artery?
Lateral aspect of LV;
aVL
Lead I
V5 and 6
43
ST elevation in which leads indicates MI in the left anterior descending artery?
Anterior aspect of the LV and interventricular septum;
V1, 2, 3, and 4.
Proximal occlusion: all
Distal occlusion: V3, 4
44
ST elevation in which leads indicates an MI in the left main coronary artery?
Gives rise to the LAD and left circumflex:
V1, 2, 3, 4
aVL
Lead I
V5, 6
45
ST elevation in which leads indicates MI in right coronary artery?
Supplies RV and inferior aspect of the LV;
Leads II, III, and aVF.
46
Where is cardiac action potential conduction speed the slowest? Fastest?
**Fastest**: Purkinje fibers
Atrial muscle
Ventricular muscle
**Slowest**: AV node
47
The middle meningeal artery is a branch of which artery?
Maxillary artery, which is one of the terminal branches of the external carotid artery.
48
Where does injury to the radial nerve occur; during what actions?
During its passage through the **supinator canal;** due to repetitive pronation/supination of the forearm (i.e., **twisting a screw driver**), direct trauma or subluxation of the radius.
49
What are signs of sepsis?
Hyper- or hypothermia, tachycardia, tachypnea (can lead to respiratory alkalosis) and leukocytosis.
Severe sepsis: organ dysfunction due to poor blood flow.
50
What does the Periodic acid Schiff stain detect?
Glycogen, mucopolysaccharides.
51
What is the volume of distribution for a large molecular weight drug, bound to proteins, highly charged (hydrophilic)?
Low (3-5L); remains in the plasma compartment.
52
What is the volume of distribution for a drug that is small MW, hydrophilic?
Medium (14-16L); can distribute to interstitial fluid compartment outside of blood vessels as well as plasma.
53
What is volume of distribution of drug that is small MW, uncharged (hydrophobic or lipophilic), bound to tissue protein?
High (41L); drug accumulates readily in tissues maintaining low plasma concentrations.
54
What is primary (psychogeneic) polydipsia?
A psychological disorder; characterized by increased intake of free water leading to hyponatremia and production of a large volume of dilute urine.
Tx: Water restriction: corrects serum Na levels and increases urine osmolality.
55
What is the presentation of Histoplasma capsulatum?
Exists as an ovoid/round yeast in the intracellular space of macrophages. Patients develop subacute pneumonia with hilar and mediastinal lymphadenopathy.
Controlled by cell-mediated immune response (caseating granulomas).
56
What is the most common side effect of diazepam?
Sedation.
57
What is chlorpheniramine?
1st generation antihistamine; blocks central and peripheral H1 receptors.
Sedation due to penetration of BBB and accumulation in the CNS.
Other histamines: diphenhydramine, hydroxyzine, and promethazine.
58
What slows the progression of hemochromatosis in women?
Physioloigic iron loss through menstruation and pregnancy.
59
What can increase Fe absorption?
Ethanol intake, ascorbic acid (Vitamin C), and citric acid.
60
What is the mechanism of action of ethosuximide?
Blocks thalamic T-type Ca2+ channels.
61
How many calories are produced from metabolism of 1g of carb/protein, alcohol and fatty acid?
1g of carb/protein = 4kcal
1g of ethanol = 7kcal
1g of fatty acid = 9kcal
62
What are withdrawal symptoms for alcohol?
Tremors, agitation, anxiety, **delirium**, psychosis.
Exam findings: **seizures**, tachycardia, palpitations.
63
What are withdrawal symptoms for benzodiazepines?
Tremors, anxiety, perpetual disturbances, psychosis, insomnia.
Exam findings: **seizures**, tachycardia, palpitations.
64
What are withdrawal symptoms of heroin?
N/v/d, abdominal cramping, muscle aches, arthralgias.
Exam findings:
**Dilated pupils, yawning,** piloerection, **lacrimation**, hyperactive bowel sounds, diaphoresis.
65
What are stimulant (e.g., cocaine, amphetamines) withdrawl symptoms?
Increased appetite, hypersomnia, vivid dreams, fatigue, **intense psychomotor retardation, severe depression ("crash").**
66
What are nicotine withdrawal symptoms?
Dysphoria, irritability, anxiety, **increased appetite.**
67
What are cannabis withdrawal symptoms?
Irritability, anxiety, depressed mood, insomnia, and **decreased appetite**.
68
Where are actin (thin) filaments in the sarcomere?
Thin (actin) filaments in the I band are bound to structural proteins at the Z line.
69
Where are myosin (thick) filaments in the sarcomere?
Thick (myosin)filaments in the A band are bound to structural proteins at the M line.
70
What does the dorsal pancreatic bud form? The ventral pancreatic bud?
Dorsal: Most of the **head**, the body, and tail of the pancreas; accessory pancreatic duct.
Ventral: **Uncinate** process, a portion of the pancreatic head, and the main pancreatic duct of Wirsung.
Remainder of the accesory duct fuses with the ventral duct to form the main pancreatic duct (of Wirsung).
71
What is a frameshift mutation?
Deletion or insertion of a number of bases that is not divisible by 3 in the coding region of a gene.
Alter the reading frame of the genetic code, resulting in the formation of nonfunctional proteins and premature stop codon.
72
What is the characteristic finding of HIV-associated dementia?
Microglial nodules: groups of activated macrophages/microglial cells formed around small areas of necrosis that may fuse to form multinucleated giant cells.
73
What is orotic aciduria?
Autosomal recessive disorder of de novo pyrimidine synthesis; due to defective uridine 5' monophosphate (UMP) synthase.
Presentation: physical and mental retardation, megaloblastic anemia, large amounts of urinary orotic acid.
Tx: uridine supplementation
74
What is displacement?
Feelings are transfered to another object or person.
75
What is the effect of CO2 on cerebral vasculature?
Low: vasoconstriction.
High: potent vasodilator of cerebral vasculature.
Tachypnea causes hypocapnia and cerebral vasoconstriction, thereby decreasing cerebral blood volume and intracranial pressure.
76
What is hepcidin?
It is synthesized by the liver.
Low levels: increased intestinal Fe absorption and stimulate iron release by macrophages.
High levels: decreases ferroportin on intestinal cells (decrease Fe absorption) and macrophages (release of iron).
77
What is the most common neurologic complication of varicella zoster virus infection?
Postherpetic neuralgia (localized dermatomal pain that persists for several months following a zoster eruption).
78
What is the mechanism of actionof latanoprost, bimatoprost?
It increases outflow of aqueous humor via decreased resistance of flow through uveoscleral pathway.
Preferred treatment for open-angle glaucoma.
79
What is expected in newborn born to HBeAg-positive mother?
High risk of acquiring perinatal HBV infection.
Have high levels of HBV replication and are at high risk for chronic infection, but are usually asymptomatic or have only mildly elevated LFTs.
80
What do the copper reduction test and glucose oxidase test detect?
Copper reduction test: **reducing** sugars (**fructose**, **glucose**, and **galactose**).
Glucose oxidase: Presence of urinary glucose.
81
What artery supplies the uterus?
Internal iliac artery: bilateral ligation of the internal iliac artery can decrease uterine blood flow and control postpartum hemorrhage unresponsive to medical management (e.g., uterine massage, uterotonic medications).
82
Describe the patent ductus arteriosus murmur.
Continuous murmur; best heard in the left infraclavicular region w/ maximal intensity at S2.
Common in patients born prematurely and those w/ cyanotic congenital heart disease.
83
What is Carcinoid Syndrome?
Most comon malignancy in the small intestine
Pathogenesis: production of vasoactive substances (**SE**, bradykinin, PGs) from the **enterochromaffin** cells of intestinal mucosa. Don't get metabolized by the liver when they metastasize to the liver (bronchial carcinoids avoid first pass metabolism as well). Most common ileal tumors. Serotonin not see if tumor if limited to GI b/c it undergoes 1st pass metabolism in liver.
Presenation: **skin flushing**, telangiectasias, cyanosis; GI - **watery diarrhea**, cramping; pulmonary- **bronchospasm**, **dyspnea**, wheezing; cardiac - valvular fibrous plaques on tricuspid (TR) and pulmonary valves (PS) (right \> left) becaues lung MAO-A breaks down serotonin before left sided heart return; syncope (due to low blood pressure); SE stimulates fibroblast growth and fibrogenesis
Histology: rosettes, **neuroendocrine** tumor markers: **chromogranin** A and **synaptophysin**
Dx: elevated 24h urinary excretion of 5hydroxyindoleacetic acid (**5HIAA**); CT/MRI of abdomen and pelvis to localize tumor; niacin deficieny (pellagra)
Tx: **octreotide** for symptomatic patients; surgery for liver metastases; octreotide is a synthetic analog of somatostain w/ longer T1/2; inhibits secretion of many hormones and hormone like substances; also used to inhibit secretory diarrhea in VIPomas (pancreatic endocrine tumors)
84
What is the impact of ethylene glycol poisoning on the kidney?
Toxic, acute tubular necrosis with p**roximal tubular cell ballooning** and **vacuolar degeneration**; presence of **calcium oxalate crystals**.
High anion gap metabolic acidosis, increased osmolar gap.
85
How do thiazide diuretics?
Decrease intravascular fluid volume, which stimulates aldosterone secretion and leads to increased excretion of potassium and hydrogen ions in the urine. Results in hypokalemia and metabolic alkalosis.
86
What is the lymphatic drainage pattern for the lower extremity?
S**uperficial inguinal nodes** drains scrotum, most cutaneous lymph from the **umbilicus** **down**, including the external genitalia and anus (below the dentate line);
DOES NOT drain the **glans** **penis** and **skin** of the **posterior** **calf** (go to **popliteal** LN) - drain to the deep inguinal LN.
Superior portion of the bladder - **external** **iliac** LN
Inferior portion of the **bladder**, **prostate** - **internal** iliac LN
Testes - **para**-**aortic** LN
Upper third of the rectum - **inferior** **mesenteric** LN
87
What is an important mechanism in aminoglycoside resistance?
Methylation of the aminoglycoside-binding portion of the ribosome, which inhibits the ability of aminoglycoside to interfere with protein translation.
88
What are type I and type II fibers?
**Type I:** slow twitch; perform actions requiring low-level sustained force (e.g., **postural maintenance**; function primarily by **aerobic metabolism**; high myoglobin (O2 storage) and mitochondrial (aerobic respiration) concentrations; examples - soleus, paraspinal muscles
**Type II**: fast twitch; generate **rapid forceful pulses of movement**; derive ATP energy through **anaerobic glycogenolysis** and subsequent glycolysis (IIb) or generate ATP via aerobic metabolism (IIa)
89
What do ANP, BNP and NO have in common?
They all activate guanylyl cyclase and increase conversion of guanosine 5'-triphosphate to cyclic guanosine 3',5'-monophosphate (cGMP).
Phosphodiesterase inhibitors (e.g., sildenafil) decrease degradation of cGMP. Elevated cGMP levels lead to relaxation of vascular smooth muscle and vasodilation.
90
What is spinal stenosis?
Abnormal narrowing of the spinal canal in the lumbar region.
Pathogenesis: degenerative arthritis; leads to narrowing of the spine due to formation of facet joint osteophytes and hypertrophy of the **ligamentum flavum**, and intervertebral disc herniation.
Presentation: lower extremity pain, numbness/paresthesia, and weakness. Pain with walking ("neurogenic claudication"); symptoms are posture-dependent. Extensnion: narrows the spinal canal, worsens symptoms; Flexion: (leaning forward) relieves pain
91
What are zinc fingers and what can bind them?
Zinc fingers are composed of chains of aa bound together around a zince atom via linkages w/ cysteine and histidine residues. Used by transcription factors to bind DNA.
Intracellular receptors that bind steroids, thyroid hormone, and fat-soluble vitamins act directly as transcription factors and contain zinc-finger binding domains.
Non-lipid soluble hormones interact with transmembrane receptors found on cell membrane and act through second messengers (ACTH, ADH, epinephrine, glucagon, insulin, and growth hormone).
92
What is acute intermittent porphyria?
Pathogenesis: Autosomal dominant; porphobilinogen deaminase deficiency; exacerbated by aminolevulinate (ALA) synthase.
ALA synthase induced by meds, alcohol use, low calorie diet.
Presentation: painful abdominal, port wine-colored urine, polyneuropathy (peripheral neuropathy), psychological disturbances, precipitated by drugs (cyp450 inducers), alcohol, starvation; no photosensitivity, port-wine colored urine, **PBG and ALA in urine.**
Tx: **glucose or hemin** inhibit ALA synthase so PBG and ALA don't build up.
93
What are the steps involved in inflammatory leukocyte accumulation?
**Margination**
**Rolling**: Neutrophils roll on endothelium via binding of sialylated carbohydrate groups such as Sialyl Lewis X or PSGL-1 to L-selectin on neutrophils or E-selectin/P-selectin on endothelial cells.
**Activation:** Chemokines lead to integrin activation.
**Tight adhesion and crawling**: Neutrophils become firmly **attached** to endothelium via binding of **CD 18 beta 2 integrins (Mac1 and LFA 1)** to **intercellular adhesion molecule-1 (ICAM1)** on endothelial cells.
**Transmigration:** Neutrophils migrate in between cells via integrin attachments and adherence to p**latelet endothelial cell adhesion molecule 1 (PECAM1)**, found on the peripheral intercellular junctions of endothelial cells.
94
What are three leukocyte adhesion deficiency (LAD) syndromes?
**LAD 1**: absence of **CD18**; affects tight adhesion, crawling, and transmigration; manifestations - recurrent skin and mucosal infections w/o pus formation, delayed detachment of the umbilical cord, and poor wound healing; **persistent leukocytosis** due to leukocytes not being able to migrate out of blood vessels
LAD 2: milder; no delay in separation of the umbilical cord, less severe, fewer infections
LAD 3: similar to type 1, severe recurrent bacterial infections, delayed separation of umbilical cod, and bleeding complications (due to affected beta3 integrins on platelets).
95
What is McCune-Albright Syndrome?
Pathogenesis: mutation of GNAS gene; constant G protein activation/cAMP/adenylate cyclase; hormone overproduction
Presentation: peripheral precocious puberty; unilateral cafe-au-lait macules; polyostotic fibrous dysplasia (lesions in many bones; bone is displaced by collagen and fibroblasts)
Complications: thyrotoxicosis; acromegaly; Cushing syndrome
96
What decreases the intensity of the HOCM murmur?
Anything that expands the LV, decreasing outflow tract obstruction: increase in preload and afterload.
Squatting (from standing position)
Sustained hand grip
Passive leg raise
97
What increases the intensity of a HOCM murmur?
Anything that **decreases LV volume**: **decrease in preload and afterload**; decreases the separation between the mitral valve and interventricular septum, increasing obstruction.
**Sudden standing** (from a sitting or supine position)
**Nitroglycerin**
**Valsalva** (straining phase)
98
What is the relationship between diabetic autonomic neuropathy and overflow incontinence?
Diabetic autonomic neuropathy is common in type 1 diabetics and can cause overflow incontinence due to inability to sense a full bladder and incomplete emptying.
Postvoidal residual (PVR) testing with US or catheterization can confirm inadequate bladder emptying.
99
How does naltrexone work in alcohol use disorder?
It blocks mu-opioid receptor; blocks the rewarding and reinforcing effects of alcohol; reduces **craving** for alcohol; can be initiated while individual is still drinking.
First-line treatment for moderate to severe alcohol use disorder.
100
What is pulmonary vascular resistance?
The sume of alveolar and extra-alveolar resistances.
Increased lung volumes increase PVR due to longitudinal stretching of alveolar capillaries by the expanding alveoli.
Decreased lung volumes increase PVR due to decreased radial traction from adjacent tissues on large extra-alveolar vessels.
PVR is lowest at functional residual capacity.
101
What is Lynch Syndrome (Hereditary **nonpolyposis** colon cancer (HNPCC)?
**Pathogenesis:** autosomal dominant mutation in MLH1, MSH2,6, PMS 2; caused by inactivated mutation in tumor suppressor gene, deletion of remaining normal allele (2nd hit) leads to loss of heterozygosity and malignant transformation. **Mutation in DNA mismatch repair genes (MSH2, MLH1) are responsible for HNPCC.**
Presentation: cancer occurs at young age (\<50yo); family history reveals high incidence of colon cancer and extraintestinal cancers (endomerial, ovarian, and skin) in first-degree relatives.
102
What causes hypospadias?
Incomplete fusion of the urethral (urogenital) folds.
103
What causes epispadias?
Faulty positioning of th genital tubercle in the 5th week of gestation.
It becomes the penis in males and the clitoris in females.
104
What is a missense mutation?
Single base substitution that results in placement of an incorrect amino acid in a protein sequence. These mutations occur w/in the coding region of a gene and do not alter protein length.
Conservative: amino acid is replaced by another with similar biochemical characteristics. Preserve protein function unless mutation occurs in a critical gene.
105
What are transamination reactions?
They occur between an amino acid and an alpha-keto acid.
The amino acid is transferred to the alpha keto acid, and the alpha keto acid in turn becomes an amino acid.
Pyridoxal phosphate (active B6) serves as a cofacter in amino acid transamination and decarboxylation reactions.
106
What is Henock-Schonlein Purpura?
Affects boys 2-10yo after a viral or streptococcal upper respiratory infection.
Pathogenesis: Infection stimulates production of IgA antnibodies, complexes then deposit on vessel walls.
Presentation: GI - intermittent severe abdominal pain, upper and lower GI bleeding; **IgA nephropathy** (mesengaial proliferation and crescent formation); Skin - **palpable purpura** on buttocks and LE due to leukocytoclasis of cutaneous vessels; Joints - self-limited migratory **athralgias**
107
What is Phenylketonuria?
Pathogenesis: Autosomal recessive mutation in phenylalanine hydroxylase or its cofactor tetrahydrobiopterin; failure to convert phenylalanine into tyrosine results in hyperphenylalaninemia and neurologic injury
Tyrosine becomes an **essential amino acid** (cannot be synthesized de novo).
Presentation: severe intellectual disability; **seizures**, **musty body odor**; hypopigmentation involving skin (because excess Phenylalanine inhibits tyrosinase), hair, eyes and brain nuclei
Dx: newborn screeing, increase in phenylalanine
Tx: dietary restriction of phenylalanine
108
What is the course of the median nerve?
Courses between the humeral and ulnar heads of the pronator teres muscle, then runs betwen the **flexor digitorum superficialis** and the **flexor digitorum profundus** muscles before crossing the wrist within the carpal tunnel.
Proximal nerve lesions result in sensory loss over the first 3 digits and impairment of thumb flexion/opposition, flexion of 2nd/3rd digits, and wrist flexion/abduction.
109
What is drug reaction with eosinophilia and systemic symptoms (DRESS syndrome)?
Drug reaction occurring 2-8w after drug exposure. Drugs: **anticonvulsants (phenytoin, carbamazepine)**, **allopurinol, sulfonamides (sulfasalzine), and antibiotics (minocycline, vancomycin)**.
Pathogenesis: drug induced herpes reactivation followed by clonal expansion of T cells that cross-react with the drug.
Presentation: fever, generalized lymphadenopathy, facial edema, diffuse morbilliform rash.
Dx: eosinophilia
Tx: withdrawal of the drug
110
What causes respiratory alkalosis?
Arterial PaCO2 is a direct indicator of alveolar ventilation status.
**Hypocapnia (low PaCO2)** implies ongoing **alveolar hyperventilation.**
Upper airway obstruction, reduced ventilatory drive, respiratory muscle fatigue, and decreased chest wall compliance are causes of **alveolar hypoventilation and hypercapnia.**
111
What is septic shock?
Triad: **hypotension, tachycardia, tachypnea**, and **markedly elevated or decreased body temperature.**
**Early sepsis**: increased CO, peripheral vasodilation, warm extremities
**Advanced sepsis**: cool and clammy extremities, delayed capillary refill, altered mental status, and decreased urine output.
**TNF-alpha** mediates sepsis, induces the systemic inflammatory response, causes sx of sepsis and cachexia.
Other cytokines responsible for inducing systemic inflammatory response include IL1 and IL6.
112
What is gram-negative sepsis?
Caused by the release of LPS from bacterial cells during division or by bacteriolysis; LPS is not actively secreted by bacteria.
**Lipid A is the toxic component of LPS** - it causes activation of macrophages leading to release of IL1 and TNF-alpha.
**Presentation**: fever, hypotension, diarrhea, oliguria, vascular compromise, and DIC.
113
What is the course of the spinal accessory nerve?
It passes through the posterior triangle of the neck.
It innervates the sternocleidomastoid and trapezius.
Symptoms of trapezius weakness: drooping of the shoulder, impaired **abduction of the arm above the horizontal,** (due to weakness in rotating the glenoid upward) and winging of the scapula.
Injurty to the **deltoid:** **impaired abduction** of the arm at angles **below the horizontal.**
114
What is the most common cause of calcium kidney stone disease?
**Idiopathic hypercalciuria**; due to increased GI absorption, increased mobilization of Ca from bone, or decreased renal tubular Ca reabsorption.
Patients are **normocalcemic** due to intact regulation of serum Ca levels by vit. D and PTH.
Other risk factors for Ca nephrolithiasis: hyperoxaluria, hyperuricosuria, low urine volume, and hypocitraturia.
115
For insomnia, what is an example of stimulus control therapy?
Leave the bedroom if unable to fall asleep within 20 minutes.
**Goal:** to dissociate the bedroom from any **stimulating** activities that do not involve sleep and the fear of not sleeping. Focuses on eliminating stimulating bedroom activities and getting into bed only when sleepy.
116
What structures are contained in the **suspensory ligament** of the ovary (infundibulopelvic ligament)?
Ovarian artery, vein, lymphatics, and nerves.
117
What is a pilocytic astrocytoma?
Most common brain tumor in children. Low grade glioma that occurs in the **cerebellum**.
Presentation: **headaches and cerebellar** findings (loss of balance, incoordinaton).
Histology: pilocystic astrocytes with bundles of glial fibrillary acidic protein **(GFAP) positive** hairlike processes, **Rosenthal fibers**.
Gross: **cystic and solid components**
118
What is anaphylaxis?
The result of mast cell and basophil degranulation and the release of preformed inflammatory mediators - **histamine and tryptase**.
**Tryptase** is specific to **mast cells** and can be used as a marker for mast cell activation.
Pathogenesis: Cross-linking of membrane bound IgE antibodies by a multivalent antigen results in **aggregation** of the FCERI receptors, causing degranulation and release of mediators that initiate allergic response.
Presentation: hypotension, edema, tachycardia, wheezing, urticarial rash, pruritus, flushing, N/v/abdominal pain
Tx: intramuscular epinephrine, airway mgmt, antihistamines, glucocorticoids.
119
What is alkaptonuria?
Autosomal recessive disorder of tyrosine metabolism.
Pathogenesis: deficiency of **homogentistic acid dioxygenase** blocks homogentistic acid metabolism into maleylacetoacetate; prevents conversion of **tyrosine to fumarate**; increase in homogentistic acid in the urine imparts **black color to urine** if allowed to sit and undergo oxidation
Presentation: ochronosis - blue-black pigmentation in connective tissue throughout the body: in **sclerae**, **ear** **carilage**, nose, cheeks; **debilitating ochronotic arthropathy** (pigment deposition in spine and large joints; causing ankylosis, motion restriction, and significant pain)
Diagnosis: increased homogentistic acid levels in urine
120
How soon after an MI are ATP stores depleted?
ATP is rapidly depleted (**within seconds**) and lactate starts to increase.
Loss of cardiomyocyte contractility occurs w/in 60s after the onset of total ischemia.
Ischemia less than 30m: restoration of blood flow leads to reversible contractile dysfunction (myocardial stunning).
Ischemia greater than 30m: irreversible ischemic injury.
121
Which biochemical reactions take place in the cytosol? Mitochondria?
**Cytosol**: Glycolysis, fatty acid synthesis, and the pentose phosphate pathway.
**Mitochondria**: beta-oxidation of fatty acids, carboxylation of pyruvate (gluconeogensis), TCA cycle, formation of citrulline in the urea cycle.
122
What is transketolase?
An enzyme of the **pentose phosphate pathway** that uses thiamine (B1) as a cofactor to shuttle 2C fragments between sugar molecules.
123
What is the result of infacts involving the anterior protion of the medial pons?
Infarcts involveing the anterior portion of the **medial pons** can produce:
**dysarthria and contralateral hemiparesis/lower facial palsy** due to disruption of the ipsilater corticospinal and corticobulbar tracts.
Trigeminal nerve arises at the level of the **middle cerebellar peduncle** at the l**ateral aspect of the mid-pons**.
124
Which organisms test positive for the pyrrolidonyl arylamidase (PYR) test?
Group A strep: **S. pyogenes**
Enterococcus **(E. faecium and faecalis)**
125
What is the result of an inferior wall MI?
Right coronary artery perfuses **inferior wall of LV** and majority of the **right ventricle**. **Inferior wall MI** is associated with **right ventricular infarction.**
Presentation: hypotension, **distended jugular veins (elevated central venous pressure)**; lack of crackles and absence of pulmonary edema. Decrease in RV SV leads to diminished LV filling and CO, decrease in pulmonary capillary wedge pressure (reflection of LA pressure).
126
What is ankylosing spondylitis?
Chronic inflammatory condition associated with HLA-B27.
Pathogenesis: stiffness and fusion (ankylosis) of the axial joints, inflammation at the site of insertion of tendons into bone (enthesitis);
Presenation: low back pain, improves with exercise/movement, but not with rest, pain at night
respiratory - involvement of the thoracic spine and costovertebral and costosternal junction can **limit chest wall expansion** leading to hypoventilation
cardio: ascending aortitis leading to dilation of the aortic ring, aortic insufficiency
eye: anterior uveitis (pain, blurred vision, photophobia, and conjunctival erythema)
127
What is cerebral amyloid angiopathy?
The most common cause of **spontaneous** **lobar hemorrhage**, particularly in the elderly. Common sites: **occipital** (homonymous hemianopsia) **and parietal lobes** (contralateral hemisensory loss).
Pathogenesis: consequence of Beta-amyloid deposition in walls of small to medium sized cerebral arteries resulting in vessel wall weakening and predisposition to rupture.
128
Does exophthalmos in Graves disease improve with beta blockers?
No. They are not mediated by TH or adrenergic stimulation and do not respond to beta blockers.
Pathogenesis: TSH receptors are present on orbital fibroblasts, which secrete excess glycosaminoglycans leading to exophthalmos. This is immune (antibody) mediated.
Tx: Glucocorticoid therapy.
129
What is DiGeorge Syndrome?
Pathogenesis: 22q11.2 **chromosome** **microdeletion** leads to maldeveloment of the **3rd (inferior parathyroid and thymus)** and **4th (superior parathyroid)** pharyngeal/branchial pouches.
Presentation:
Conotruncal cardiac defects (Tetralogy of Fallot, truncus arteriosus, interrupted aortic arch)
Abnormal facies
Thymic hypoplasia/aplasia: **T cell deficiency** - recurrent viral, fungal, and protozoan infection
Craniofacial deformities (cleft palate)
**Hypocalcemia** - increased neuromusclar excitability (tetany, carpopedal spasms, seizures); twitching of nose and lips afater tapping on CN7 (Chvostek sign) and carpal spasm after **inflation of BP cough** (Trousseau sign)
Dx: **fluorescence in situ hybridization** is the "**gold** **standard**" for detecting a microdeletion
130
What is the mechanism behind Turner Syndrome?
Meiotic nondisjunction during gametogenesis.
131
What is a proto-oncogene?
Normal gene that is converted into oncogene by **1-hit gain of function** mutation. They stimulate cell proliferation, and their overexpression/amplification (e.g., **activating mutation**) leads to increased cellular proliferation and neoplastic growth. Need damage to **only one allele**.
Pathogenesis: deletion/point mutation, gene amplification, chromosome rearrangement
Ex: ABL, BRAF, ERBB1 (EGFR), ERBB2 (Her2), RAS, KRAS, MYC
132
What is a tumor suppressor?
Anti-oncogenes, they inhibit cellular proliferation. Their inactivation (e.g., **loss of function mutation**) contributes to tumor development.
**Both alleles** must be lost for expression of disease.
Ex: **APC, BRCA1/2, RB, TP53, WT1, VHL.**
133
What is chronic non-atrophic gastritis?
Most often due to H. pylori infection. It affects the gastric antrum.
Associated with an increased risk of peptic ulcer.
Involvement of the gastric body in longstanding infection is assoc. w/ an increased risk of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma.
Acute phase: neutrophils; chronic: lymphocytes, lymphoic follicles, and plasma cells.
134
What is pernicious anemia?
It occurs in **autoimmune atrophic chronic gastritis**. Characteristically affects the **body** of the stomach rather than the antrum.
Autoimmune destruction of parietal cells causes decreased intrinsic factor production and impaired vitamin B12 absorption.
135
How does nitroprusside work in hypertensive emergency?
It is a short acting **venous and arterial vasodilator**. So, it **decreases LV preload and afterload** without reduction in stroke volume. It does not directly alter cardiac contractility.
136
What is cardiac tamponade?
Pathogenesis: malignancy, infection, drugs, connective tissue diseases
Presentation: **Beck's triad** - hypotension with pulsus paradoxus, elevated JVP, and muffled heart sounds
Pulsus pardoxus: abnormal exaggerated decerase in systolic blood pressure \>10mg Hg on inspiration
RV expands into the interventricular septum toward teh left ventricle, so LVEDV and SV decrease leading to decrease in systolic pressure during inspiration.
Dx: ECG - low voltage QRS complexes, electrical alternans;
CXR - enlarged water-bottled shaped heart, **clear lungs**
137
What is constrictive pericarditis?
Pathogenesis: Caused by scarring and loss of elasticity of normal pericardial sac; RV can't expand into pericardial space w/ increased venous return, so it bows into the LV space which leads to a decrease in LVEDV and SV, w/ a resultant **decrease in systolic pressure during inspiration**; radiation therapy to chest, cardiac surgery, TB
Takes several weeks to months to develop and only rarely occurs after recurrent episodes of acute pericarditis.
**Pulsus paradoxus** can occur: **\>10mmHg drop** in systolic pressure during inspiration; the difference between systolic pressure at which Korotkoff sounds first become audible during expiration and the pressure at which they are heard throughout all phases of respiration
Presentation: slowly progressive **dyspnea**, **peripheral** **edema**, **ascites**
Labs: CT scan (**thickening** and **calcification** of pericardium)
138
What are the cardiac findings in Turner Syndrome?
Aortic coarctation, bicuspid aortic valve;
Presentation: lower-extremity claudication (e.g., pain and cramping w/exercise), BP discrepancy between upper and lower extremities, and delayed or diminished femoral pulses, continuous murmurs and pulsatile intercostal collaterals
139
What is primary hemochromatosis (hereditary hemochromatosis)?
Impaired iron sensing
Pathogenesis: missensce mutation in HFE gene (C282Y), **inactivating mutation in HFE protein**; normally interacts with the transferrin receptor on hepatocyte to form a complex that functions as a sensor of iron stores. Inactivating HFE mutation leads to reduced Fe uptake and causes enterocytes and hepatocytes to detect falsely low Fe levels. Leads to Fe overload by:
1. Enterocytes: upregulate DMT1, increasing Fe absorption from GI lumen
2. Hepatocytes: decrease hepcidin synthesis, which increases ferroportin expression on basolateral enterocyte surface
Presentation: accumulation of iron in end-organ tissues; hemosiderin accumulation
Labs: excessive Fe accumulation results in elevated levels of serum ferritin (cellular Fe storage protein) and increased saturation of transferrin (major Fe transporter in plasma)
Complications: increased risk for liver cirrhosis and hepatocellular carcinoma
140
What is varenicline?
A partial agonist of nicotinic acetylcholine receptors. Competes with nicotine and prevents it from binding. Assists pts with cessation of tobacco use by reducing withdrawal cravings (mildly stimulates the receptor).
Attenuates the rewarding effects of nicotine by causing limited downstream release of dopamine. Better than the patch.
141
What is prepatellar bursitis?
Bursa: fluid-filled synovial sac that alleviates pressure and friction at bony prominences and ligamentous attachments.
Prepatellar bursa is located between the patella and the overlying skin. Due to repetitive anterior knee trauma from kneeling (housemaid's knee).
Suprapatellar: located anteriorly between the distal femur and quadriceps. Bursitis here is caused by direct blow to distal thigh or prolonged/repetitive quadriceps activity (running).
142
What is an atrial complication of aortic stenosis?
Acute atrial fibrillation.
In pts with chronic AS and concentric LVH, atrial contraction contributes to LV filling. Loss of atrial contraction due to atrial fibrillation reduces LV preload and CO to cause systemic hypotension.
Decreased forward filling of the LV can also result in backup of blood in the LA and pulmonary veins, leading to acute pulmonary edema.
143
What is the presentation of congenital adrenal hyperplasia?
Vomiting, hypotension, hyponatremia, hyperkalemia.
Males: normal genitalia.
Females: ambiguous genitalia at birth.
144
What is the origin of the spleen?
It is of **mesodermal orgin** (the dorsal mesentery); intraperitoneal organ.
Blood supply derives from **foregut derivative** (the splenic artery off of celiac trunk).
Most common intra-abdominal organ injured during blunt trauma.
145
What are the outcomes of insulin intracellular signaling?
Insulin acts via receptor tyrosine kinase, activates:
MAP kinase - promotes mitogenic functions (DNA synthesis and cell growth)
Phosphatidylinositol-3-kinase (PI3K) - stimulates metabolic functions (translocation of GLUT4 to cell membrane, glycogen synthesis, fat synthesis)
Glycogen synthesis due to activating **protein phosphatase**, an enzyme that dephosphorylates (activates) **glycogen synthase**.
146
What is inulin?
A substance that is **freely filtered** at the glomerulus.
It is neither reabsorbed nor secreted by the renal tubules.
It is used to calculate the GFR.
147
How does a vitamin C deficiency present?
Deficiency (scurvy) is characterized by **perifollicular hemorrhages, myalgias, subperiosteal hematoma, gingivitis**, and impaired wound healing.
Ascorbic acid (vit. C) is a cofactor in the hydroxylation of proline and lysine residues; important in the synthesis of collagen.
148
What is effect modification?
It occurs when the effect of an exposure on an outcome is modified by another variable. It can be identified using stratified analysis (analyzing the cohort as different subgroups), as the different strata will have different measures of association.
149
What is a confounder?
It is associated with both exposure and outcome and affects the measure of association between exposure and outcome, such that there initially appers to be a statistically significant associationi between the two variables. However, once the results are stratified by the confounding variable, the association disappears.
150
What is atropine?
An **anticholinergic agent** that competitively inhibits acetylcholine at the muscarinic acetylcholine receptor.
Effects: blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, full as a flask, and fast as a fiddle.
Tx: Can be reversed by **cholinesterase inhibitors** (physostigmine).
151
What is xeroderma pigmentosum?
Autosomoal recessive disorder due to a defect in **nucleotide excision repair.**
Presentation: increased sensitivity to UV radiation, especially the face; skin shows atrophy, telangiectasias, and intermingling areas of hypo-hyperpigmentation due to chronic UV damage.
High incidence of cutaneous malignancy.
152
What is the difference in origin of replication between eukaryotes and prokaryotes?
Eukaryotes: multiple orgins of replication
Prokaryotes: a single origin of replication
153
What is hormone-sensitive lipase?
It is found in adipose tissue where it functions to drive the breakdown of stored triglycerides into **glycerol and free fatty acids**. During times of starvation, this enzyme provides substrates for hepatic gluconeogenesis and ketone body formation.
Stimulators: catecholamines, glucagon, ACTH
Inhibitors: Insulin
154
What is required for the growth of Haemophilus?
Gramy-negative coccobacilli; It requires **X factor (hematin) and V factor (NAD+)**.
Sheep blood agar does not allow it to grow due to insufficient nutrients and the V factor-inactivated enzymes in the medium.
S. aureus added to medium allows H to grow because S. aureus **secretes V factor (NAD+)** and facilitates release of additional X factor from Beta-hemolysis-induced RBC lysis ("satellite" phenomenon).
155
Describe the sarcomere.
A band: contains both thin (actin) and thick (myosin) filaments; remains the same length during muscle contraction
H band: part of the A band; thick filaments only; shortens during muscle contractions
I band: thin filaments; shortens during muscle contractions
M line: midline of the thick filaments
Z line: midlineof the thin filaments
156
What is community acquired pneumonia?
Presentation: new-onset fevers, productive cough, dense lobar infiltrate, green sputum
Neutrophil **myeloperoxidase** produces **green color of pus and sputum**. It is a blue-green heme based pigment molecule released from azurophilic granules and forms hypochlorus acid (bleach).
157
What is cyanide poisoning?
Pathogenesis: Occurs in patients treated with nitroprusside
Presentation: altered mental status, seizures, cardiovascular collapse, **lactic** **acidosis**, and bright red venous blood; **reddish skin discoloration**, tachypnea, HA, tachycardia, N/V, weakness; narrowing of venous-arterial PO2 gradient due to inability of tissue to extract arterial O2
Antidote: 1. **Hydroxocobalamin** (directly binds cyanide ions)
**2. Sodium nitrate** (induction of **methemoglobinemia (Fe3+)**, combines cyanide to form cyanmethemoglobin, which is excreted in the urine); increases hemoglobin's affinity for cyanide,
3. **Sodium thiosulfate** (detoxifying sulfur donors - promotes hepatic rhodanese-mediated conversion of cyanide to **thiocynate**, which is excreted in the urine)
158
What is propionic acidemia?
Pathogenesis: autosomal recessive; congenital deficiency of **propionyl-CoA carboxylase**, which converts propionyl CoA to methylmalonyl CoA.
Presentation: 1-2w after birth; metabolic acidosis, hypoglycemia, ketosis, lethary, poor feeding, vomiting, hypotonia
Tx: low-protein diet with low amounts of **isoleucine, methionine, threonine, and valine**
159
What is rodenticide?
Most rodenticides contain brodifacoum, a long-acting 4 hydroxycoumarin derivative **(superwarfarin)**.
Presentation: ingestion leads to coagulopathy and abnormal bleeding (similar to warfarin toxicity).
Tx: Immediate administration of **fresh frozen plasma** in addition to vitamin K.
160
What is the mechanism of actionof ezetimibe?
It decreases intestinal absorption of cholesterol by inhibiting the Niemann-Pick C1-like 1(NPC1L1) transporter protein, which transports dietary cholesterol from the GI lumen into the intestinal enterocytes.
Consequently, the amount of dietary cholesterol reaching the liver decreases. To compensate, the liver increases LDL receptor expression, which draws cholesterol out of circulation.
161
What is adenomyosis?
Pathogenesis: the presence of endometrial glandular tissue **within the** **myometrium**.
Presentation: **painful**, **heavy menstrual bleeding** due to an increased endometrial surface, and dysmenorrhea due to endometrial tissue growth confined to myometrial space; **uniformly enlarged uterus** due to hormonal stimulation of endometrial glandular tissue in myometrium
162
What defects are caused by a patent processus vaginalis?
Communicating **hydroceles** and i**ndirect inguinal hernias** are caused by an incomplete obliteration of the processus vaginalis.
Resultant connection between the scrotum and abdominal cavity can allow for fluid leakage (hydrocele) or the passage of abdominal contents (indirect inguinal hernia).
163
What is the role of eosinophils against parasites?
They play a role in host defense during parasitic infection. When stimulated by antibodies bound to a parasitic organism, they destroy the parasite via **antibody-dependent cell mediated cytotoxicity** with enzymes from their cytoplasmic granules.
Another function of eosinophils is regulation of type 1 hypersensitivity reactions (late), this is not protective against parasites.
Type 1 hypersensitivity reactions are primarily mediated by mast cells and basophils.
164
What is the volume status of patients with SIADH?
Presentation: low plasma Na and osmolality, inappropriately concentrated urine, and clinically normal volume status (**euvolemic hyponatremia**).
An important cause of SIADH is a paraneoplastic effect secondary to small cell carcinoma of the lung.
165
What is the effect of ethanol on the citric acid cycle?
Metabolism of ethanol by alcohol dehydrogenase and aldehyde dehydrogenase consumes NAD+ and increases the NADH to NAD+ ratio; inhibits all pathways requiring NAD+ and the entire TCA cycle is inhibited (NADH doesn't need to be made anymore).
Pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase require thiamine as a cofactor. Chronic alcholics are deficient in thiamine.
Administration of glucose to thiamine deficient pt can result in Wernicke encephalopathy (acute confusion, ophthalmoplegia and ataxia) due to increased thiamine demand.
166
What is Sheehan Syndrome?
Peripartum hypotension can cause ischemic necrosis of the pituitary leading to panhypopituitarism.
Pathogenesis: high estrogen levels during pregnancy cause enlargment of the pituitary gland without a proportional increase in blood supply.
Presentation: failure of lactation due to deficiency of prolactin
167
What is pituitary apoplexy?
It is due to sudden hemorrhage into the pituitary, usually in the setting of a preexisting pituitary adenoma.
Presentation: acute severe headache, ophthalmoplegia, and altered sensorium.
168
What is congenital hypothyroidism?
It is usually asymptomatic at birth. After maternal T4 wanes, infants develop constipation, lethargy, hypotonia, macroglossia, nonpitting edema (puffy face) an umbilica hernia, and a large anterior fontanelle.
Pathogenesis: thyroid dysgenesis (agenesis, hypoplasia, or ectopy); iodine deficiency
Diagnosis: high TSH, low free T4 levels
Tx: levothryroxine by age 2 weeks
169
Damage to what structure can cause contralateral sensory loss?
The ventral posterior thalamus.
Ventral **posterior lateral** nucleus: receives input from the **spinothalamic tract and dorsal columns.**
Ventral **posterior medial** nucleus: receives input from the **trigeminal pathway**
Both send **somatosensory** projections to the cortex via thalamocortical fibers.
170
What are lacunar infarcts?
Lacunes are small fluid filled cavitary infarcts located w/in the basal ganglia, posterior limb of the internal capsule, pons, and cerebellum.
Pathogenesis: infarcts result from **occlusion of small penetrating arteries** that supply deep brain structures; risk factors - chronic uncontrolled HTN or DM, smoking.
Lipohyalinosis and microatheromas and hardening/thickening of the vessel wall (**hypertensive arteriolar sclerosis**) are the primary causes of lacunar infarcts. They predispose to thrombotic vessel occlusion.
**Lipohyalinosis**: due to leakage of plasma proteins through damaged endothelium; hyaline thickening of vascular wall
**Microatheromas**: due to atherosclerotic accumulation of lipid-laden macrophages in intimal layer
Both lead to small vessel occlusion, infarction of CNS tissue w/ liquefactive necrosis and formation of fluid-filled cavity.
171
What are the stages of acute tubular necrosis?
**Initiation stage:** ischemic injury to renal tubules precepitated by hemorrhage, acute MI, sepsis, surgery
**Maintenance stage:** decreased urine output, fluid overload, increasing creatinine/BUN, hyperkalemia
**Recovery phase** (polyuric)**:** gradual increase in urine output leading to high volume diuresis; electrolyte abnormalities may include decreased concentrations of **K, Mg, PO4, and Ca** due to slowly recovering tubular function
**Hypokalemia** is the most serious complication of recovery phase.
172
What is serotonin syndrome?
Presentation: autonomic instability (hyperthermia, HTN, tachycardia), altered mental status, and neuromuscular hyperactivity (hyperrefleixa, myoclonus)
Pathogenesis: develops when a MAOI antidepressant or a non-antidepressnat with MAOI activity (Linezolid) is combined with a serotonergic med such as an SSRI, SNRI, or tricyclic depressant.
**Linezolid has MAOI activity.**
173
What is reactive arthritis?
Preceding infection: GU infection - c. trachomatis, enteritis0 salmonella, shigella, yersinia, campy, c. difficile
Presentation: **urethritis, conjunctivitis, mono or oligoarticular arthritis;** can also present with keratoderma blennorrhagicum (hyperkeratotic vesicles on the palms and soles, sacroilitis
Pathogenesis: seronegative (rheumatoid factor negative) spondyloarthropathy associated with HLAB27; sx manifest 1-4w **after** a primary infection causing urethritis or enteritis and are caused by autoimmune reaction initiated by infecting pathogen
Tx: self limited, anti-inflammatory agents, or antibiotics for chlamydia
174
What is actinomycosis?
Slowly progressive disease caused by gram-positive anaerobic bacteria, **actinomyces**.
Organisms typically colonize the mouth, colon, and vagina; can be found in dental caries and at margins of gums in poor dentition;
Pulmonary actinomycosis develops following aspiration; can be confused with lung abscess, malignancy, or tuberculosis
Microscopic findings: filamentous, branching, gram-positive bacteria, sulfur granules (appear amorphous, basophilic)
Tx: Penicillin
175
What is a paradoxical embolism?
It occurs when a thrmbus from the venous system crosses into the arterial circulation via an abnormal connection between the R and L cardiac chambers (e.g., patent foramen ovale, atrial septal defect or ventricular septal defect.
A cerebrovascular event (e.g., TIA, stroke) in setting of known venous thromboembolic disease is suspicious for paradoxical embolism.
Atrial left to right shunts cause wide and fixed splitting of S2 and can facilitate paradoxical embolism due to transient shunt reversal (during straining or coughing).
176
Where is GTP made in the TCA cycle?
GTP is synthesized by **succinyl CoA synthethase** during conversion of succinyl CoA to succinate.
During gluconeogenesis, phosphoenolpyruvate carboxykinase uses GTP to synthesize phosphoenolpyruvate from oxaloacetate.
177
What is subclavian steal syndrome?
It occurs due to **severe stenosis of the proximal subclavian artery,** (on the left side) which leads to reversal in blood flow from the contralateral vertebral artery to the ipsilateral vertebral artery.
Presentation: patients may have symptoms related to arm ischemia in the affected extremity (e.g., exercise-induced fatigue, pain, paresthesias) or vertebrobasilar insufficiency (e.g., dizziness, vertigo).
178
What is the management of patients with diabetic ketoacidosis?
Most patients with DKA have **normal to increased serum potassium** levels despite a total body potassium deficit.
Replacement of K is a crucial step in the management of patients with diabetic ketoacidosis.
179
What is eosinophilic granulomatosis with polyangitis (Churg Strauss)?
Small to medium vessel vasculitis.
Presentation: Late onset **asthma, rhinosinusitis, and eosinophilia**. Asymmetric multifocal neuropathy (**mononeuritis multiplex**) common due to vasculitis affecting epineural vessels.
Labs: anti-neutrophil myeloperoxidase (p-ANCA)
180
What is hemophilia A/B?
Inheritance: X-linked recessive
Presentation: delayed/prolonged bleeding after mild trauma or procedure; hemarthrosis, hemophilic arthropathy; intramuscular hemorrhage; GI or GU tract bleeding
Labs: prolonged activated PTT, normal platelet count, bleeding time, PT; decreased or absent factor 8 (A) or factor 9 (B) activity
Tx: administration of factor 8 or factor 9; demopressin for mild hemophilia A
181
What is central pontine myelinolysis?
Result of rapid correction of chronic **HYPOnatremia**; osmotic demyelination of axons in the central part of the pons
Presentation: **spastic quadriplegia** due to myelination of the corticospinal tracts and pseudobulbar palsy due to demyelination of the cortibulbar tracts of CN 9, 10, and 11 (head and neck muscle weakness, dysphagia, and dysarthria, nuclei of CN remain intact).
**Cerebral edema** results from rapid correctioni of **HYPERnatremia.**
