18 month old boy with a normal development until 5 months of age. Gradual regression of developmental milestones like inabililty to sit without support, poor head control, and loss of a social smile. Enlarged spleen and liver, diminshed deep tendon reflexes in all limbs, hypotonia, cherry red macula.
Sphingomyelinase deficiency --> sphingomyelin accumulation within lysosomes (look like lipid laden foam cells)
An elevated creatinine kinase (CK) is highly suggestive of what underlying problem?
Due to direct myocyte damage and leakage of muscle enzymes into the circulation
Common causes of myopathy with elevated CK
Inflammatory muscle diseases
Medications like statins
Autoimmune diseases (polymyositis, dermatomyositis)
Muscle pain and stiffness in shoulder, neck, and pelvic girdle. Worse in the morning and with activity. Normal Creatinine Kinase
What drug should be given to a patient with recurrent calcium oxalate stones?
They effectively increase calcium reabsorption from the nephron
34 y/o man with severe chest and abdominal pain then suffers a cardiac arrest with pulseless electrical activity, internal hemorrhage was the COD. Autopsy shows a defect in a large extracellular glycoprotein normally found in abundance in large blood vessels, periosteum, and zonular fibers of the lens and functions to form microfibrils by surrounding elastin.
Defect in Fibrillin-1 - a major component of microfibrils that form a sheath around elastin fibers.
Heart = aortic dilation, regurgitation, or dissection, mitral valve prolapse
What drug decreases intestinal absorption of cholesterol by inhibiting the neimann-pick C1-like 1 (NPC1L1) transporter protein, which transports dietary cholesterol from the brush border of the small intestine?
In a person with Cyanide poisoning, the use of amyl nitrite has what effect?
It oxidizes ferrous (Fe2+) in hemoglobin to ferric (Fe3+), generating methemoglobin which is incapable of carrying oxygen but has a high affinity for cyanide so it sequesters cyanide in the blood, freeing it from cytochrome oxidase and limiting it's toxic effects.
Other than amyl nitrite, what substances can be used as antidotes for cyanide poisoning?
Hydroxycobalamin (vit B12 precursor)
What step in Vitamin D metabolism is directly affected by being in the sun?
Conversion of 7-dehydrocholesterol to Cholecalciferol
Newborn with intracranial, gastrointestinal, cutaneous, umbilical, or surgical site bleeding. What is lacking?
Babies should be given intramuscular vitamin K because there is low vit K at birth due to poor placental transfer, low content in breast milk, and a sterile gut.
Vit K is critical for carboxylation of clotting factors 2, 7, 9, 10
Child with spontaneous by painless lower GI bleeding. Tc-pertechnetate localizes ectopic gastric mucosa and it's increased uptake is diagnostic for what?
Failed obliteration of the vitelline (omphalomesenteric) duct
Colicky abdominal pain with currant jelly (strawberry jam appearance) stools.
(meckel diverticulum can lead to this)
A frontal lobe lesion on what side causes apathy and depression?
Left-sided frontal lobe
A frontal lobe lesion on what side causes disinhibited behavior?
Right-sided frontal lobe lesion
Femoral hernias are between what 3 structures?
Inferior to the inguinal ligament
Lateral to the pubic tubercle
Medial to the femoral vein
What is the most important environmental risk for pancreatic cancer?
von Willebrand factor serves what 2 roles in hemostasis?
1. Promotes platelet adhesion at sites of vascular injury by binding to and crosslinking platelet glycoproteins (primarily Gp 1b) with exposed collagen underneath damaged endothelium.
2. Protective carrier protein for factor 8 that increases it's plasma half-life
Langhans giant cells are characteristic of granulomatous conditions, including the caseating granulomas associated with Mycobacterium tuberculosis infections. The macrophages that form these giant cells are activated by what?
CD4+ Th1 Lymphocytes
Chronic antral inflammation leads to a decrease in the number of somatostatin-producing cells (delta cells). What will be the result?
Uninhibited gastrin release
Increased hydrogen ion secretion by parietal cells
Duodenal ulceration and duodenal gastric metaplasia
What are the common side effects of ACE inhibitors?
Angioedema (rare but life threatening)
What is the course of the ureters and what structures are near them?
Within retroperitoneum just anterior to the psoas muscles. Midway from the kidnes to the pelvic inlet, gonadal artery and vein cross over the anterior surface of the ureter.
The ureters gain access to the pelvis by crossing over the anterior surface of the common iliac artery near its bifurcation into the internal and external iliac arteries. At this point, the ureter lies medial to the ovarian vessels and anterior to the internal iliac artery.
MOA of combined hormonal contraceptive pills?
Suppress GnRH and pituitary gonadotropin secretion, inhibiting ovulation
Acute coronary syndrome occurs due to plaque rupture, which leads to superimposed thrombosis and vessel occlusion. The likelihood of plaque rupture largely depends on the mechanical strength of the fibrous cap. What characterizes low strength?
Thin-cap fibroatheromas have large necrotic core covered by a thin fibrous cap. Activated macrophages infiltrating the atheroma contribute to the breakdown of ECM by secreting metalloproteinases. Ongoing intimal inflammation can destabilize the mechanical integrity of the plaque through release of these metalloproteinases, resulting in plaque rupture and consequent acute coronary syndrome.
What is the MOA of Acyclovir?
Complete inhibition of the viral DNA polymerase
What is the most characteristic skeletal manifestation of primary hyperparathyroidism? How does it present?
Osteitis fibrous cystica
Bone pain, subperiosteal erosions affecting the phalanges of the hand and a salt and pepper skill, and brown tumor bone cysts.
What mutation leads to constitutive activation of the epidermal growth factor receptor pathway, promoting increased cell proliferation and growth?
Activating mutations of the KRAS gene
What is the difference between major depressive disorder and persistent depressive disorder?
Persistent = at least 2 years
Major = at least 2 weeks
Painful thyroid enlargement following a viral illness. Pts experience a transient hyperthyroid phase due to release of stored thyroid hormone. What is the diagnosis and what does biopsy show?
Subacute granulomatous (de Quervain) thyroiditis
Biopsy = lymphocytic infiltrate with macrophages and multinucleated giant cells
Rivaroxaban and Apixaban are oral anticoagulants that work on what?
Directly inhibits factor Xa
Used in venous thromboembolism and a-fib
What is the treatment of choice for DKA? What are the lab changes after treatment?
Intravenous normal saline and insulin
Increase serum bicarb and sodium, decrease serum glucose, osmolality, and potassium
A pt. with a persistent belief that he is being poisoned, general function is not disturbed. No presence of psychotic symptoms like hallucinations. (greater than 1 month in duration)
If a right to left intracardiac shunt is found what are the 2 most common lesions that would cause this?
1. Atrial Septal Defect
2. Patent Foramen Ovale
A patent foramen ovale remains functionally closed and therefore asymptomatic unless what would happen?
Conditions that raise the right atrial pressure above the left atrial pressure (valsalva) can produce a transient right to left shunt across the PFO that may result in a paradoxial embolism (stroke in the setting of venous thromboembolism)
54 y/o previously healthy man with 2 months of progressive, generalized weakness and easy fatigability, abdominal discomfort, early satiety, afebrile, pallor, abdominal distension, massive splenomegaly with the spleen tip crossing the midline, pancytopenia, dry tap on bone marrow aspiration.
Hairy Cell Leukemia
Lymphocytes with cytoplasmic projections
Predominantly middle aged men
Fibrosis --> pancytopenia
Flow cytometry has replaced TRAP staining for diagnosis
What is found on autopsy/histo after an amniotic fluid embolism?
Fetal squamous cells and mucin in the maternal pulmonary arteries
What bleeding disorder will cause a prolonged PTT and bleeding time?
von Willebrand Disease
AD with variable penetrance
Most common heritable bleeding disorder.
What is a carrier protein for factor 8 and a mediator of platelet adhesion to the endothelium?
Von Willebrand Factor
A transmural infarction is most commonly caused by what events?
Acute plaque change (rupture) which produces a superimposed thrombus that completely occludes the involved coronary artery.
What are the 3 aspects of MEN 1?
Primary hyperparathyroidism (hypercalcemia)
Pituitary tumors (prolactin, visual defects)
Pancreatic tumors (gastrinomas)
What are the 3 aspects of MEN 2A?
Medullary thyroid cancer (calcitonin)
What are the 3 aspects of MEN 2B?
Medullary Thyroid Cancer (calcitonin)
Mucosal neuromas/marfanoid habitus
What antifungals bind to ergosterol molecules in fungal cell membranes, creating pores and causing cell lysis?
What antifungals inhibit synthesis of ergosterol?
What antifungals inhibit the synthesis of glucan, a component of the fungal cell wall?
What antifungal is converted to 5-FU within the fungal cell and interferes with fungal RNA and protein synthesis?
Pt with perifollicular hemorrhages, myalgias, subperiosteal hematoma, and gingivitis
Deficient ascorbic acid (Vit C)
C is important in the hydroxylation of proline and lysine residues (needed for collagen synthesis)
What vitamin deficiency leads to angular stomatitis, cheilitis, glossitis, seborrheic dermatitis, eye changes (keratitis, corneal neovascularization), and anemia?
B2 - Riboflavin
What deficiency causes acrodermatitis enteropathica, growth retardation and infertility?
Arterial blood supply to the myocardium is provided by the right and left coronary arteries arising directly from the aortic root during what?
When HR goes up, duration of diastole goes down --> major limiting factor for coronary blood supply to the myocardium
Under hypoxic conditions, intracellular accumulation of NADH inhibits what enzyme of glycolysis? What way pyruvate shunted?
Pyruvate Dehydrogenase is inhibited
Pyruvate goes to lactic acid (via lactate dehydrogenase)
With significant tissue ischemia, lactate begins to accumulate in the circulation and can lead to lactic acidosis.
Riboflavin is a precursor of what coenzymes? Where are they important?
FMN and FAD
FAD acts in the TCA cycle and electron transport chain as an electron acceptor for succinate dehydrogenase (succinate --> fumarate)
The common cardinal veins of a developing fetus give rise to what?
SVC and other constituents of the systemic venous circulation
Overdose findings: mental status changes (delirium, drowsy, coma), seizures, respiratory depression, tachycardia, hypotension, arrythmias, dry mouth, blurry vision, dilated pupils, flushing, hyperthermia.
Due to blockage of cardiac fast sodium channels and inhibition of muscarinic acetylcholine, histamine, and alpha-1-adrenergic receptors
Treat = Sodium Bicarb
Which MHC class is loaded with antigen taken into an APC within acidified endosomes and then expressed on the cell surface for subsequent interaction with T lymphocytes?
Sickle cells patients are at an especially increased risk of infection by what organisms?
Encapsulated organisms because they are asplenic!
If a sickle cell patient is septic, pick one of these.
Elderly woman with abdominal pain/distention, nausea/vomit, high-pitched (tinkling) bowel sounds, tenderness to palpation, dilated loops of bowerl with air-fluid levels, air in biliary tree (pneumobilia). (symptoms of a small bowel obstruction.... but that isn't what she has)
Formation of a cholecysteneric fistula between the gallbladder and adjoining gut. Fistula formation allows passage of gallstone into small bowel, where it travels freely until it becomes trapped in the ileum (narrowest portion of intestine)
Benign leukocytosis (>50,000) that occurs in response to an underlying condition. Leukocyte alkaline phosphatase levels are normal or increased. What is this reaction and what is found on peripheral blood smear?
Smear = increased bands, early mature neutrophil precursors (myelocytes), granules (dohle bodies - basophilic oval inclusions in mature neutrophils)
What is the pathogenesis of gallstones in a pregnant woman or a woman using OCPs?
Estrogen-induced cholesterol hypersecretion
Progesterone-induced gallbladder hypermotility
(FAT, FERTILE, FEMALE, FORTY)
How does Etanercept work?
TNF-alpha inhibitor added to methotrexate for RA
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.
What is the pathogenesis of amenorrhea in a woman with excessive weight loss, strenuous exercise, chronic illness, or an eating disorder? (functional hypothalamic amenorrhea)
Decreased adipose tissue/fat reserves
Decreased Leptin Production
Hypothalamus = decreased GnRH
Pituitary = decreased LH, FSH
Ovaries = decreased Estrogen
Amenorrhea, bone loss
A crycothyrotomy is indicated when an emergency airway is required and orotracheal or nasotracheal intubation is not available. What structures will be penetrated (out to in)?
Superficial cervical fascia (subQ fat + platysma muscle)
Investing and pretracheal layers of deep cervical fascia
(all done between cricoid and thyroid cartilages)
An increasing prevalence and stable incidence can be attributed to what?
Factors that prolong the duration of a disease
The anthracycline chemotherapy agents (doxorubicin, daunorubicin, epirubicin, and idarubicin) have what SE on the heart?
Form free radicals in the myocardium
Cumulative dose-related dilated cardiomyopathy
(symptoms of left and right ventricular CHF)
Poisoning: abdominal pain, vomiting, severe watery diarrhea, hypotension, garlic odor to breath. Chronic = pigmentation change, hyperkeratosis, stocking glove neuropathy
Mechanism: binds sulfhydryl groups and disrupts cellular respiration and gluconeogenesis
Sources: pesticides, contaminated water, pressure treated wood
Treatment = Dimercaprol
Carbon Monoxide poisoning has what effect on these values:
Carboxyhemoglobin = elevated
PaO2 and Methemoglobin = normal
Small cell carcinoma of the lung (oat cell) is the most aggressive type of lung cancer. What is it's origin and what markers could be seen?
Neuroendocrine markers: neural cell adhesion molecule (NCAM aka CD56), neuron-specific enolase, chromogranin, synaptophysin
Colitis associated carcinoma is more likely to:
1. Affect younger pt
2. Start from flat and non-polypoid dysplasia
3. Appear mucinous or be signet ring
4. early p53 mutations, late APC mutations
5. In prox colon
6. Be multifocal
6 y/o boy with recurrent sinopulmonary and gastrointestinal infections, failure to thrive, and evidence of defective signaling between CD4+ T cells and B cells
Hyperimmunoglobulin M Syndrome
Defect in class switching in B lymphocytes due to defective CD40-CD40L interaction
X linked recessive deficiency of CD40L is most common
34 y/o man: one week of inability to extend his right wrist and several of his fingers on the same hand. History of late onset asthma. Eosinophils elevated. Serum antibodies against neutrophil myeloperoxidase.
Eosinophilic granulomatosis with polyangiitis (Churg Strauss)
Asymmetric multifocal neuropathy (mononeuritis multiplex) is common due to the vasculits affecting the epineural vessels.
45 y/o man with groin pain and swelling. 1 month ago he had a sore on his penis (painless) that disappeared within a week. Now he has painful swelling in his inguinal region with inflammation overlying the skin and formation of several draining ulcers. Mild fever + malaise. Scrapings reveal cytoplasmic inclusion bodies.
Clamydia Trachomatis (L1-L3)
Lymphogranuloma Venereum (LGV)
Large, painful, coalesced inguinal lymph nodes (buboes)
Intracytoplasmic chlamydial inclusion bodies in epithelial cells and leukocytes
Treat = Doxy