Week 2 Flashcards
Which cerebral artery territory would be most affected by an occlusion of the right internal carotid artery?
The watershed territory between the ACA and MCA. The internal carotid artery supplies blood to both the anterior cerebral artery and the middle cerebral artery. Decreased blood supply to both would most severely damage the tissue that lies between these arteries, known as the watershed zone. You would see leg/upper arm weakness and defects in higher-order visual processing
In a normal distribution what percent falls within 1 SD? 1.96 SD? 2.58 SD?
1 SD - 68%
- 96 SD - 95%
- 58 SD - 99%
Uvula is innervated by which CN? Does it deviate towards or away from the lesion?
Palatal arches and uvula - mediated by the vagus nerve (CN X)
Deviation is contralateral for LMN (away from the lesion)
Toward the lesion if UMN
What is kernicterus?
Bilirubin (unconjugated) toxicity in the CNS that occurs in some newborns with severe jaundice. It is characterized by neurologic deficits including hypotonia, lethargy, and poor reflexes. Albumin binds unconjugated bilirubin in the blood and the albumin-bilirubin complex is then unable to pass through the BBB. Low levels of albumin could result in kernicterus. This can also occur with a deficiency of the hepatic enzyme uridine diphosphate-glucoronyl transferase that conjugates bilirubin.
Wilson’s disease
How is it inherited? Characteristics? Treatment?
AR disease of copper metabolism (deficiency of ceruloplasmin - major storage protein for copper)
Excess copper is deposited in the liver, brain and other tissues -> basal ganglia (neuropsychiatric), iris (Kayser-Fleischer rings), and liver (liver failure).
Long-term management includes copper chelation therapy with D-penicillamine and eventual liver transplant
Can cause hepatocellular carcinoma and/or dementia
Perioral numbness/tingling, Chvostek’s sign (facial spasm) and Trousseau’s sing (carpal spasm with BP cuff) are all signs of what?
Hypocalcemia
Does calcitonin increase or decrease calcium levels?
Decreases (opposes PTH) - decreases bone resorption of Ca++. Not important in normal Ca++ homeostasis. CalciTONin TONes down Ca++ levels
Rubeola is also known as…
Measles
Prodrome of measles? What spots appear? 3 C’s?
Rash that spreads head to toe over a 3 day period that begins 1 or 2 days after Koplik’s spots develop - red oral lesions with white centers
3 C’s: Cough, coryza (runny/stuffy nose), conjunctivitis (+Koplik’s spots)
What characterizes diphtheria?
Caused by corynebacterium diphtheriae
Characterized by a pseudomembranous pharyngitis (life threatening cause of sore throat)
Roseola characterized by? Believed to be caused by?
Febrile disease of very young children that begins with a high fever and progresses to a rash similar to measles. Infants and children are most at risk. Believed to be caused by human herpesvirus 6
Rubella is also known as
German measles (a less severe viral exanthem) many infections are subclinical but rubella can cause severe birth defects when infection occurs during the prenatal period
Friedreich’s ataxia
Caused by?
Effects?
A trinucleotide repeat disease (GAA). Unstable microsatellite regions regions on certain chromosomes have triplet codons that expand, worsening from generation to generation (increasing onset - anticipation)
Causes a decrease in the translation of a gene on chromosome 9 that encodes frataxin (iron binding protein)
Leads to impaired mitochondrial functioning. Degeneration of multiple spinal cord tracts -> muscle weakness and loss of DTRs, vibratory sense and proprioception. Staggering gait, frequent falling, nystagmus, dysarthria, pes cavus (high arch), hammer toes, hypertrophic cardiomyopathy (cause of death). Presents in childhood with kyphoscoliosis (abnormal curvature of the spine in sagittal and coronal directions)
Friedreich is Fratastic (frataxin): He’s your favorite frat brother always stumbling, staggering and falling but has a big heart.
Azathioprine - MOA? SE? Use?
Immunosuppressant that inhibits purine synthesis and metabolism
Antimetabolite precursor of 6-mercaptoPURINE
MOA: inhibits lymphocyte proliferation by blocking nucleotide synthesis
SE: anemia, thrombocytopenia, leukopenia (susceptibility to infection)
Uses: transplant rejection prophylaxis, RA, Crohn disease, glomerulonephritis and other autoimmune conditions, long-term control of IBD
How do thiazolidinediones work?
Oral hypoglycemics that increase peripheral sensitization to insulin by binding and modulating the activity of nuclear transcription factors called peroxisome proliferator-activated receptors (PPARs). They also decrease hepatic gluconeogenesis.
What is a common complication following group B strep infection in neonates?
Meningeal scarring may occur damaging the arachnoid villi so that they are not able to absorb CSF resulting in a communicating (non obstructive) hydrocephalus
Hepatocellular carcinoma/hepatoma (HCC)
What is it? Associated with? Findings? How to dx? How does it spread?
What: Most common primary malignant tumor of the liver in adults
Associated with: HepB, HepC, Wilson disease, hemochromatosis, alpha-one-antitrypsin def., alcoholic cirrhosis and carcinogens (alfatoxin from Aspergillus). May lead to Budd-Chiari Syndrome
Findings: jaundice, tender hepatomegaly, ascites, anorexia
Diagnosis: Increased AFP, ultrasound or contrast CT
Spreads: hematogenously
HCC, renal cell carcinoma, and follicular throid carcinoma spread how?
Hematogenous dissemination
Hodgkins lymphoma, many benign neoplasma and some sarcomas spread how?
Contiguous spread without metastasizing to distant sites
What cancers disseminate through the peritoneal cavity? What is this characterized by?
Ovarian and appendiceal cancers can disseminate directly through the peritoneal cavity
This process is known as pseudomyxoma peritonei and is characterized by a diffuse collection of gelatinous materials in the abdomen, peritoneal surfaces and pelvis
What cancers typically spread via lymphatics?
Breast, colon, papillary thyroid, melanoma
What congenital heart defect is associated with maternal diabetes?
Transposition of the great vessels
(aorticopulmonary septum fails to spiral during development) - newborn will have immediate cyanosis
Machine-like murmur? Treated with? Associated with?
Patent ductus areriousus
Indomethacin
Congenital rubella
Right to left shunts (congenital heart diseases) - 5
Early cyanosis - blue babies. Often diagnosed prenatally or become evident immediately after birth. Usually require urgent surgery and/or maintenance of a PDA
- Truncus arteriousus (1 vessel)
- Transposition (2 switched)
- Tricuspid atresia
- Tetralogy of fallot
- TAPVR (5 letters in the name)
What is TAPVR?
Total anomalous pulmonary venous return (TAPVR) Pulmonary veins drain into right heart circulation (SVC, coronary sinus); associated with ASD and sometimes PDA to allow for R-to-L shunting to maintain CO
Tetralogy of fallot
(PROVe) Pulmonary stenosis RVH (boot shaped heart on CXR) Overriding aorta VSD
Femoral hernias are more common in who?
FEMales
Protrudes below inguinal ligament through femoral canal
Indirect inguinal hernia are more common in who? Where do they occur?
INfants
Goest through internal (deep) inguinal ring, external (superficial) inguinal ring and into scrotum. Occurs in infants (males usually) due to failure of the processes vaginalis to close (can form hydrocele). Enters internal inguinal ring lateral to inferior epigastric artery
Direct inguinal hernia - where does is lie in relation to the inferior epigastric artery?
Protrudes through the inguinal (Hesselbach) triangle. Bulges directly through abdominal wall medial to inferior epigastric artery. Goes through the external (superficial) inguinal ring only. Covered by external spermatic fascia. Usually in older men
MDs don’t LIe
Medial to inferior epigastic artery = Direct
Lateral to inferior epigastric artery = Indirect
Diaphragmatic hernia
Abdominal structures enter the thorax, may occur in infants as a result of defective development of pleuroperitoneal membrane. Most commonly a hiatal hernia, in which the stomach herniates upward through the hiatus of the diaphragm
Sliding hiatal hernia - most common, gastroesophageal junction is displaced upward, hourglass stomach
Paraesophageal hernia - gastroesophageal junction is normal, funds protrudes into the thorax (to the side of the esophagus but still through the hiatus)
SE of Salmeterol/formoterol?
Tremor and arrhythmia (heart palpitations)
Ipratropium/tiotroprium - Use? Mechanism? SE?
Muscarinic antagonist that competitively blocks muscarinic receptors preventing bronchoconstriction.
SE: cough, anxiety, dry mouth, nausea
Mostly used for COPD but can be used for asthma
What is a methylxanithine used for asthma? How does it work? Risks? Metabolized by?
Theophylline
Likely causes bronchodilation by inhibiting PDE -> increases cAMP levels due to decreased cAMP hydrolysis. Usage is limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity); metabolized by cytochrome P450. Blocks actions for adenosine
2x - blocks adenosine and cAMP breakdown (PDE)
What is the first line therapy for chronic asthma? Mechanism?
Corticosteroids (beclomethasone, fluticasone)
Inhibit the synthesis of virtually all cytokines. Inactivate NF-kB, the transcription factor that induces the production of TNF-alpha and other inflammatory agents (block the late response and bronchial hyperactivity)
Antileukotrienes for asthma treatment - drugs? mechanism? best for?
Montelukast, zafirlukast - block leukotriene receptors. Especially good for aspirin-induced asthma
Zileuton - a 5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to leukotrienes
Lithium toxicity
LMNOP: Lithium side effects Movement (tremor) Nephrogenic diabetes insipidus HypOthyroidism Pregnancy problems
Anticonvulsant/antimanic drug that can cause agranulocytosis and other hematologic abnormalities?
Carbamazepine
Signs of pancreatic cancer? Associated with what tumor marker?
Weight loss, painless jaundice, migratory thrombophlebitis (swelling and warmth that moves to different parts of the body)
CA-19-9
Trousseau’s syndrome
Hypercoagulability (leading to migrating DVTs and vasculitis)
Associated with pancreatic adenocarcinoma
Courvosier sign
Obstuctive jaundice with palpable nontender gallbladder (nontender means unlikely to be gall stones, associated with pancreatic adenoma)
Where does GLUT4-mediated glucose transport occur? GLUT-1? GLUT-2? GLUT-5?
4- Adipose and skeletal muscle tissue (insulin dependent - the only two that are)
1- Cortical neurons (independent of insulin), RBCs (independent of insulin), cornea
2- Pancreatic B cells (serve as glucose sensors), liver, kidney, SI
5- spermatocytes, GI tract
What takes up glucose independent of insulin?
BRICK L
Brain, RBCs, Intestine, Cornea, Kidney, Liver
Megaloblastic, macrocytic anemia - two principle causes? Which is more common and why? What process is then interrupted?
Vitamin B12 (cobalamin) or folate deficiency Folate deficiency is more common because folic acid stores are depleted by the body rather quickly The tetrahydrofolate form of folate (folic acid) functions as an intermediate in the transfer of one-carbon units (important for purine synthesis)
Glutathione deficiency results in…
Glutathione is an antioxidant that requires NADPH to regenerate. Glucose-6-phostphate dehydrogenase (G6PD) is crucial in providing a cell with the NADPH necessary to restore glutathione. Its deficiency results in increased susceptibility to oxidative stress/injury, formation of heinz bodies and development of a normocytic, hemolytic anemia with characteristic “bite” cells (Heinz bodies removed by spleen)
Pernicious anemia
Most common cause of vitamin B12 deficiency (macrocytic)
Autoimmune destruction of parietal cells (body of stomach) leads to intrinsic factor deficiency (necessary for B12 absorption)
How to distinguish B12 from folate deficiency?
Both have hyper segmented neutrophils, glossitis, decreased folate or B12, and increased homocysteine (Vit B12 transfers a methyl group originally from folate to homocysteine)
Neurologic symptoms are seen with B12 only (involvement in fatty acid pathways and myelin synthesis)
Methylmalonic acid is increased in B12 but normal in folate def. (conversion to succinylo CoA requires B12)
What are some antifolate drugs that could results in folate deficiency?
Phenytoin, methotrexate, trimethoprim
25% of patients with celiac sprue (autoimmune intolerance to wheat) suffer from what skin condition? What is it due to? What will you see microscopically?
Dermatitis herpetiformis - pruitic, vesicular rash on extremities (herpes like - vesicles and bullae that are grouped)
Due to IgA deposition at the tips of dermal papillae
Microscopic findings including blunting of SI villi and lymphocytic infiltrates in the lamina propria
What is tested for in celiac disease?
Anti-gliadin (wheat) antibodies
What is bullous phemigoid caused by? What does it look like?
Caused by IgG antibody against epidermal BM (destruction of hemidesmosomes between BM and basal cells).
Presents with multiple, fluid-filled, non ulcerating bullae (blisters of the skin) and affects the skin while sparing the oral mucosa
Do not rupture easily, seen in the elderly
What is Pemphigus vulgaris?
A potentially fatal autoimmune skin disorder consisting of intra-epidermal (destruction of desmosomes between keratinocytes) ulcerating bullae involving the oral mucosa and skin. Common findings are acantholysis and IgG antibody directed against the epidermal surface
Thin walled, rupture easily
Fish net on immunofluorescence (IgG surrounding keratinocytes)
What do patients with selective IgA deficiency present with?
Sinus and lung infections (IgA is the most prominent immunoglobulin found in mucous membranes)
What is hyper-IgM syndrome caused by? What results?
A defect in the CD40 ligand on CD4 T helper cells - inability to class switch (x-linked rec) IgM is high and all other isotypes are low Severe pyrogenic infections early in life, opportunistic infections with CMV, pneumocystis cryptoporidium
What is Chediak-Higashi disease?
An inherited AR disease characterized by failure of phagolysosome formation. Due to a defect in lysosomal trafficking regulator gene (LYST). Because phagocytksed bacteria are not destroyed by the lysosome’s enzyme, patients often present with recurrent streptococcal and staphylococcal infections. Partial albinism may be present (melanosomes are derivatives of lysosomes) .
Chronic granulomatous disease
Increased susceptibility to?
What is defective?
What test confirms the diagnosis of CGD?
Increased susceptibility to infections by microbes that produce their own catalase (PLACESS) Pseudomonas Listeria Aspergillus Candida E. coli S. aureus Serratia
Defective neutrophil phagocytosis due to a lack of NADPH oxidase activity (decreased ROS - absent respiratory burst)
A negative nitroblue tetrazolium dye reduction test confirms the diagnosis of chronic granulomatous disease
Giant cell tumor: Malignant or benign? Most commonly occurs in? Occurs where? X-ray shows? Composed of?
Benign bone tumor
Most commonly occurs in woman 20-40 years old
Most commonly occurs at the epiphyseal end of longs bones (distal femur or proximal tibial)
X-ray shows a double bubble or soap bubble sign
Composed of oval or spindle shaped cells with scattered multinucleated giant cells
Osteochondroma:
Malignant or benign?
Most commonly occurs in?
Describe the bone tumor
Most common benign tumor
Occurs in men <25 years old
Mature bone with cartilaginous cap. Rarely transforms to chondrosarcoma
Ewing sarcoma: Malignant or benign? Most commonly occurs in? Occurs where? Outlook? Describe appearance Associated with what translocation?
Anaplastic small blue cell malignant tumor
Occurs in boys <15 years old
Commonly appears in diaphysis (middle) of long bones, pelvis, scapula and ribs
Extremely aggressive with early metastases, but responsive to chemo
Onion skin appearance in bone
Associated with t(11;22) translocation (11+22=33, Patrick EWINGS jersey number)
Chondrosarcoma: Malignant or benign? Most commonly occurs in? Occurs where? Appearance?
Rare, malignant, cartilaginous tumor
Men 30-60 years old
Usually located in the pelvis, spine, scapula, humerus, tibia or femur
May be of primary origin or from osteochondroma
Expansive glistening mass within the medullary cavity
Osteosarcoma: Malignant or benign? Most commonly occurs in who? Predisposing factors? Occurs where? Radiological findings? Treatment?
2nd most common primary malignant bone tumor (after multiple myeloma)
Bimodal distribution: 10-20 year olds (primary), >65 (secondary)
Predisposing factors: Paget disease of bone, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome (germ line p53 mutation)
Metaphysis of long bones, often around knee
Codman triangle (from elevation of periosteum) or sunburst pattern on x-ray
Aggressive. Treat with surgical en bloc resection (w/ limb salvage) and chemotherapy
What is nodular glomerulosclerosis? What is it characterized by? Who is this seen in? What else do these patients show?
Accumulation of nodules in the mesangial matrix (pathognomonic for DM)
Characterized by Kimmelstiel-Wilson nodules in the mesangial matrix
It can be seen in patients with long-standing, untreated DM
Also shows increased BM thickness and diffuse mesangial matrix proliferation
What is the most common cause of bacterial meningitis in babies?
Group B streptococci (Group B is for Babies!)
25% of woman’s vaginal canals are colonized - test for GBS and give antibiotics prophylactically to prevent infecting neonate
Machine like murmur?
PDA
Loud, harsh or blowing holosytolic murmur over left sternal border in 3rd/4th intercostal space?
Ventricular septal defect
A fixed and widely split S2 is pathognomic for…
An atrial septal defect
Split second heart sound indicates a certain amount of blood is passing from the LA to the RA on every beat. Normally inspiration leads to increased blood in the RV, causing delay of the closure of the pulmonic valve and expiration decrease blood in the RV, leading to earlier closure of the pulmonic valve (increased flow through pulmonic valve such that regardless of breath, pulmonic closure is greatly delayed)
Atrial septal defect can lead to a…
paradoxical embolus (embolus from right side of heart passes to the left side and subsequently embolizes in the left MCA)
Midsystolic crescendo-decresecendo murmur best heart at right second intercostal space?
Aortic stenosis
Three equations for CO
CO = SV x HR
CO = (rate of oxygen consumption) / (arterial oxygen - venous oxygen)
CO = MAP/TPR
SV equation
SV = EDV - ESV
Calculating HR from R-R interval
HR (beats/min) is equal to the inverse of the R-R interval (seconds/beat)
So if R-R is 0.8
HR = 1 beat/0.8 sec = 1.25 beats/sec x 60 secs = 75 beats/min
Autosomal dominant polycystic kidney disease:
What is it? How does it present? Mutation in what? Death from? Associated with?
Innumerable cysts causing bilateral enlarged kidneys (destroy parenchyma)
Presents w/ flank pain, hematuria, HTN, urinary infection, progressive renal failure
Mutation in PKD1 (85%, chrom 16) or PKD2 (15%, chrom 4)
Death from complications of chronic kidney disease or HTN (caused by increased renin)
Associated with berry aneurysms, mitral valve pro laps, benign hepatic cysts
AD or AR polycystic kidney disease is diagnosed at a young age?
AR - diagnosed in pediatric patients, AD average onset is age 30
Vitamin B12 deficiency symptoms and blood smear findings
Neurologic abnormalities (not seen in folate deficiency): ataxic gait, hyperreflexia, loss of position and vibration sense (dorsal columns), mental changes
Hypersegmented neutrophils (folate deficiency as well)
Why do you see neurologic abnormalities in B12 deficiency but not folate deficiency?
B12 is involved in the fatty acid pathways and myelin synthesis
