UWorld Journal Flashcards
copper reduction test
nonspecifically detects presence of reducing sugar such as fructose, glucose, and galactose
essential fructosuria
benign, autosomal recessive disorder causes some of dietary fructose load to be secreted in urine unchanged due to defective metabolism by fructokinase (so deficient in Aldolase B)
hypocalcemia symptoms
paresthesias (lips, mouth, hands, and feet), muscle twitching or cramps
worsening–> trismus or tetany with changes in mental status and generalized seizures
insulin types
basal long acting: glargine (once daily) and NPH (twice daily)
short acting: lispro (peak 2-3 hrs), aspart (peak 2-3 hours), regular (peal 30-90min, best for postmeal)
Calcitriol
active form of vitamin D
chosen over calcidiol because the conversion of calicidiol to calcitriol is dependent on parathyroid hormone
what are thiazolidinediones?
lower glucose by reducing insulin resistance by upregulating genes
takes several days to weeks to observe significant reduction in glucose
genes upregulated by thiazolidinediones
- glucose transporter-4 (GLUT4)= insulin-responsive transmembrane glucose transporter expressed in adipocytes and skeletal myocytes
- adiponectin= cytokine secreted by fat tissue that increases the # of insulin-responsive adipocytes and regulates fatty acid oxidation
metformin functions by
acting as a noncompetitive inhibitor of mitochondrial glycerol-3-phosphate dehydrogenase–> significant reduction in hepatic glucose production
risk of radioactive iodine-131
significant tissue damage to throid gland–> radiation induced hypothyroidism and thyroid carcainoma
treat with potassium iodide
Wolff-Chaikoff effect
large increases in serum iodide levels inhibit iodine organification –> reduce thyroid hormone release
medullary thyroid cancer
enlarged thyroid nodule with elevated calcitonin level
calcitonin from the parafollicular C cells
multiple endocrine neoplasia 2B (MEN2B) diseases
mucosal neuromas, marfanoid habitus (arm span>height, long fingers, joint laxity) medullary thyroid cancer, pheochromocytomas
Pheochromocytomas symptoms
paroxysmal hypertension, flushing, diaphoresis, and headaches due to episodic secretion of catecholamines
5 P’s: Pressure (hypertension), pain (headache), perspiration, palpitations, and pallor (alpha1 vasoconstriction)
Cushing disease
ACTH-secreting pituitary adenoma
Cushing syndrome is just increased cortisol due to different things
characteristics of papillary carcinoma cells
large wtih overlaping nuclei containing finely dispersed chromatin (ground glass appearance aka Orphan Annie eye)
lots of intranuclear inclusion bodies and grooves
psammoma bodies (laminated calcium deposits)
biopsy of subacute granulomatous thyroiditis (de Quervain thyroiditis)
early- neutrophilic infiltrate with microabscess formation
then- lymphocytic infiltrate with macrophages and multinucleated gian cells
Conn syndrome
aldosterone-producing adrenal adenoma leading to primary hyperaldosteronism
aldosterone escape phenomenon
high aldosterone levels–> increased intravascular volume–> increased renal blood flow and augmented release of atrial natriuretic peptide.–> increased sodium excretion by the renal tubues–> limits net sodium retention and prevents the development of overt volume overload and significant hypernatremia
histopathological characteristic of gynecomastia
ductal epithelial hyperplasia surrounded by dense stromal fibrosis
common pathologic causes of gynecomastia
- obesity (increased aromatase conversion of testosterone to estrogen)
- hyperthyroidism (increased LH secretion and estrogen production)
- cirrhosis (increased aromatse activity, decreased clearance of estrogens)
- chronic kidney disease (decreased testosterone production)
tamoxifen
*selective estrogen receptor modulator
inhibits effects of estrogen on breast tissue
*efficient for preventing and treating gynecomastia in patients on androgen-deprivation therapy
*increase risk for endometrial hyperplasia and cancer
Spironolactone
K+ sparing diuretics
potent antiandrogen that decreases testosterone production and inhibits the testosteone receptor
commonly used to treat heart failure
side effect- gynecomastia, decreased libido, and impotence
deficiency of dihydrobiopterin reductase
- the enzyme necessary to convert phenylalnine to tyrosine and from tryosine to DOPA
- hyperphenylalanemia and elevated prolactin
- impaired phenylalanine hydroxylase activity and low dopamine levels from impaired tyrosine hydroxylase activity
tyrosinase deficiency
causes albinism
melanin is synthesized in melanocytes from tyrosine by tyrosinase
proximal tubules reabsorb ____ % of water filtered by the glomeruli
> 60%
ADH acts on which part of the kidney
collecting ducts to change how much more water it needs to reabsorb (additional water reabsorption to the reabsorption that happens in the proximal tubules)
Goodpasture syndrome
combined presentation of renal failure and pulmonary hemmorhage in patients with anti-glomerular basement membrane
*autoantibodies against alpha 3 chain of type IV collagen
anti-glomerular basement membrane (anti-GBM) disease
nephritic
deposits composed of IgG and C3
anti-GBM antibodies target collagen type IV, a component of the glomerular basement membrane–> subsequent complement deposition–> rapidly progressive (crescentic) glomerulonephritis
Glomerular cresents composed of
proliferating parietal cells with an infiltration of monocytes and macrophages are seen on ligh microscopy
Erythropoiesis-stimulating agents
- treat anemia of chronic kidney disease
- increased risk for thromboembolic events due to increased blood viscosity
- hypertension
Vasopressin effects on urea
vasopressin activates urea transporters in the medullary collecting duct–> increaseing urea reabsorption and decreasing renal urea clearance (allows for the production of maximally concentrated urine)
most comomon pathologic cause of unilateral fetal hydronephrosis
narrowing or kinking of the proximal ureter at the ureteropelvic junction
chronic renal allograft rejection results in
obliterative intimal thickening, tubular atrophy, and interstitial fibrosis
hyperacute transplant rejection due to
preformed antiboies against graft
see gross mottling and cyanosis, arterial fibrinoid necrosis and
capillary thombotic occlusion
acute transplant rejection due to
exposure to donor antigens induces humoral/cellular activation of naive immune cells
- humoral:C4d deposition, neutrophilic infilitate, necrotizing vasculitis
- cellular: lymphocytic interstitial infiltrate and endotheliitis
chronic transplant rejection due to
low-grade immune response refractory to immunosuppressants
- vascular wall thickening and luminal narrowing
- interstitial fibrosis and parenchyma atrophy
Graft vs host disease
- commonly seen with bone marrow transplantation
- when competent donor T-cells transplanted into an immunocompromised patient and subsequently attack the recipient’s organs
acidosis stimulates what in the kidneys
-renal ammoniagenesis (process where renal tubular epithelial cells metabolize glutamine to glutamate, generating ammonium that is excreted in urine and bicarb that is absorbed into blood)
multiple schlerosis develop _________ a few weeks after developing an acute lesion of the spinal cord
spastic bladder (due to presence of upper motor neuron lesion in spinal cord)
increased urinary frequency and urge incontinence
ACE inhibitors (-pril) block ACE and cause
- decrease the conversion of angiotensin I to angiiotensin II
- increase bradykinin levels
ACE inhibitors effects on creatinine
acute rise in serum creatinine by blocking angiotensin mediated efferent arteriold vasoconstriction
–> reduction in renal filtration fraction–> can lead to renal failure if patients are dependent on efferent arteriole constriction
how can humans acquire schistosomiasis?
-contact with freshwater sources that contain snails infected with Schistosoma larvae
- S japonicum and S mansoni cause intestinal and hepatic schistosomiasis
- S haematobium cuases urinary schistosomiasis
virus carried by bats
rabies
filtration fraction (FF)
fraction of plasma flowing through glomeruli filtered across the glomerular capillaries into Bowman’s space
FF=GFR/RPF (renal plasma flow=RPF)
RPF= RBF*(1-Hematocrit)
most of the K+ filtered by the glomeruli is resorbed where
proximal tubule and loop of Henle
late distant and cortical collecting tubules are the primary sites for regulation of K+ concentration in the urine
aldosterone - where does it act in the kidney
acts on the principal and intercalated cells of the renal collecting tubules to cause resorption of soidum and water and loss of potassium and hydrogen ions
aldosterone receptor antagonists
sprionolactone and eplerenone
important side effect: gynecomastia
signs of hyperaldosteronism
hyertension, hypokalemia, metabolic alkalosis and decreased plasma renin activity
detrusor overactivity
cause urge incontinence–> frequent urge to urinate
renal cell carcinoma- findings
hematuria, renal mass of proximal tubules, malignant cells on histopathology
genetic component of renal cell carcinoma
most are sporatic
some are associated with von Hippel-Lindau (VHL) disease (autosomal dominant disorder due to deletion or mutation of the VHL tumor suppressor gene on chromosome 3p)
Somatic pain from appendicitis
inflammed appendix irritates the parietal peritoneum and abdominal wall to cause more severe somatic pain that shifts from umbilical region to McBurney point (2/3 of distance from umbilicus to anterior superior iliac spine)
3 types of groin hernias
direct inguinal, indirect inguinal, and femoral
direct and indirect inguinal occurs above the inguinal ligament
femoral occurs below inguinal ligament
femoral hernias location
lateral to pubic tubercle and lacunar ligament
medical to femoral artery and vein
more common in women and tend to occur on the right side
VIPoma
vasoactive intestinal peptide
–> watery diarrhea, hypokalemia, and achlorhydria syndrome(absence of HCl in gastric secretions) (pancreatic cholera)
VIP stimulates pancreatic bicarb and chloride secretion, and its binding to intestinal epithelial cells leads to adenylate cyclase activation and increased cyclic AMP production, causing sodium, chloride, and water secretion into the bowel
somatostatin
aka octreotide
decreases production of many GI hormones
Cholecystokinin
causes increased secretion of pancreatic enzymes and bicarb, gallbladder contraction, and inhibition of gastric emptying
produced by I cells of the proximal small bowel mucosa in response to fatty acids and amino acids
Hepatitis A virus
most commonly silent or subclinical in young children
can present as acute, self-limited illness characterized by jaundice, malaise, fatigue, anorexia, nausea, vomiting, RUQ pain, or aversion to smoking
what kills cells with decreased or absent MHC class I proteins on their surfaces?
Natural killer cells
Natural killers cells activated by
interferon-gamma and IL-12
Small intestinal bacterial overgrowth (SIBO)
- characterized by overproduction of vitamin K and folate–> nausea, bloating, ab discomfort, and malabsorption
- caused by gastric bypass
test for Meckel diverticulum
99mTc-pertechnetate scan
increased uptake of 99mTc-pertechnetate in the periumbilical/RLQ
cause of Meckel diverticulum
ileal outgrowth due to failed obliteration of the vitelline (omphalomesenteric) duct
why do fructose have a faster metabolism compared to other carbohydrates?
it bypasses a major regulatory step in glycolysis (phosphofructokinase)
number of cells needed for Shigella to cause disease
as few as 10-500 cells
Shigella is able to invade tissues and is highly adapted to surviving the acidity of stomach and bacteriostatic action of bile
most prominent organisms isolated from intraabdominal infections
Bacteroides fragilis and E. coli
Vibrio cholerae (description of cells and where they are found)
- oxidase-positive, gram-negative, comma shaped organism
- found in contaminated food or water ingestion
- treat with fluid replacement
Vibrio cholerae- what does the cholera toxin do?
activates adenylate cyclase in intestinal epithelial cells–> increased cyclic adenosine monophosphate, enhanced chloride efflux and decreased dosium reabsorption
induces mucin ejection by goblet cells–> causes massive, water diarrhea with mucus and sloughed epithelial cells
how does lactase deficiency lead to watery diarrhea?
undigested lactose accumulate in small intestine–> increase in secretion of water and electrolytes in intestinal lumen
how can carcinoembryonic antigen (CEA) be used to help monitor colon cancer recurrence?
a glycoprotein involved in cell adhesion
elevated initial CEA levels associated with worse prognosis
higher in smokers
cause of annular pancreas
- abnormal migration of the ventral pancreatic bud
- second part of the duodenum surrounded by ring of pancreatic tissue
- the annular pancreas can compress the duodenal lumen or obstructed pancreatic drainage (acute or chronic pancreatitis)
Aspergillus flavus and Aspergillus parasiticus
produce aflatoxins and grow on food–> consumption strongly associated with hepatocellular carcinoma
p53 mutations G:C–>T:A transversaion in codon 249
Lactase deficiency and pH
- fermentation of undigested lactose –> production of short-chain fatty acids that acidify the stool (decrease stool pH)
- produce hydrogen gase (increased breath hydrogen content)
anterior vs posterior duodenal ulcers
anterior wall of the duodenal bulb prone to perforation
posterior wall pront to hemorrhage
duodenal ulcers more common than gastric ulcers
artery associated with posterior duodenal wall
gastroguodenal artery
artery located behind the posterior duodenal wall so can when eroded by duodenal ulcers, cause upper gastrointestinal bleeding
vitamin E deficiency
vitamin E protect fatty acids from oxidation
so deficiency cause oxidative injury, especially neurons with long axons and erythrocytes
–>neuromuscular dz and hemolytic anemia
production of intrinsic factor
parietal cells int he body and fundus of stomach
binds to vitamin B12 to form complex that is absorbed in terminal ileum
long-term hyperglycemia most likely contributed to cataract formation by causing
oversaturation of polyol pathway
polyol pathway: (first step is to convert glucose into sorbital by aldose reductase, which gets converted slowly to fructose with sorbitol dehydroenase)
too much glucose –> too much sorbital that can’t be converted to fructose fast enough
How does sorbitol accumulatioin due to hyperglycemia leads to diabetic retinopathy, neuropathy, and nephropathy?
increases cellular osmotic and oxidative stress
insulin suppresses ________ by directly actin on the alpha cells
glucagon
gene mutation assoicated with DiGeaorge syndrome
22q11.2 microdeletion
impaired development of which embryonic structures associated with DiGeorge Syndrome
Third pharyngeal pouch–affects inferior parathyroid and thymus
Fourth pharyngeal pouch- affects superior parathyroid
leads to hypocalcemia and T cell deficiency
DiGeorge Syndrome-hypocalcemia increased ________ excitability
- ->tapping on facial nerve elicits twiching of nose and lips (_______ sign)
- -> inflation of blood pressure cuff leads to carpal spasm (_________sign)
neuromuscular, Chvostek, Trousseau
low bone density and vaginal dryness are common sequelae of decreased _________
estrogen
if hyperprolactinemia is not treated, prolonged hypogonadism (low estrogen) causes:
accelerated bone loss–> fragility fractures
what is maple syrup urine disease? (genes)
autosomal recessive disorder characterized by the defective breakdown of branched-chain amino acids (leucine, isoleucine, and valine)
maple syrup urine disease: mutations in branched-chain alpha-ketoacid dehydrogenase complex result in accumulation of ______________ in ___ and _________tissues
branched chain amino acids; serum; peripheral
–> neurotoxicity that includes seizures, irritability, lethargy, and poor feeding
the sweet odor of the urine in maple syrup urine disease due to:
metabolite of isoleucine
Branched-chain alpha-ketoacid dehydrogenase (in addition to pyruvate dyhydrogenase and alpha-ketoglutarate dehydrogenase)requires 5 cofactors:
Thiamin, Lipoate, Coenzyme A, FAD, NAD (mnemonic: Tender Loving Care for Nancy)
some patients with maple syrup urine disease improve with high dose thiamine treatement wtih lifelong dietary restrictions
why would long term glucocorticoid use decrease cortisol?
–> atrophy of hypothalamic CRH- releasing neurons, pituitary corticotrphic cells, and adrenal zona reticularis and zona fasciulata ==> acute adrenal insufficiency (adreanl crisis)
have low CRH, ACTH, and cortisol
Why does T3 levels remain normal in hypothyroidism?
T3 has short half-life and conversion of T4 to T3 in peripheral tissues can be variable, T3 levels fluctuate
serum T3 levels often remain normal until relatively late-stage hypothyroidism
what is maturity-onset diabetes of the young and what is the enzyme that is mutated?
mild-nonprogressive hyperglycemia that often worsens iwth pregnancy-induced insuline resistance.
mutation with glucokinase
Becuase the symptoms of pheochromocytoma result form increase catecholamine secretion, the symptoms are ____________ due to fluctuations in catecholamine synthesis by tumor
episodie
symptoms: headache, tachycardia/palpitations, sweating, hypertension
three components of craniopharyngioma
solid, comprised of actual tumor cells
cyctic, filled with “machinery oil” liquid
calcified component
tumor arising from remnants of Rathke’s pouch
how does craniopharyngioma leads to hyperprolactinemia
compression of pituitary stalk–> loss of dopaminergic inhibition so hyperprolactinemia
also cause hypopituitarism
risk of pancreatitis rises with increasing _____________
triglyceride
pancreatic lipase metabolize triglycerdies to free fatty acids, which have toxic and inflammatory effects on pancreas
_________ are the most effective agents for treatment of hypertriglyceridemia
fibrates (eg. fenofibrate)
____________ is characterized by a mixed cellular infiltrate with occasional multinuclear giant cells
Subacute (de Quervain, granulomatous) thyroiditis
_________________ is characterized with mononuclear infiltrate consisting of lymphocytes and plasma cells, often with germinal centers, residual follicles surrounded by Hurthle cells (large oxyphilic cells filled with granular cytoplasm)
Hashimoto thyroiditis
methimazole and propylthiouracil inhibit ___________________, enzyme responsible for both iodine organification and coupling of idotyrosines
thyroid peroxidase
thyroid peroxidase is the enzyme responsible for both
iodine organification and coupling of idotyrosines
mealtime insulin analogs (eg. lispro, aspart, glulisine) with amino acide substitution at __ terminal end of the ____
C, B
____________ an oxidase-positive, non-lactose-fermenting, Gram-negative oranism (common cause of UTI with indwelling bladder catheters)
Pseudomonas aeruginosa
acute renal allograft rejection is associated with diffuse ________ infiltration of the renal _________, _______, and _______
lymphocytic; vasculature (endotheliitis), tubules, and interstitium
why is inulin clearance commonly used to calculate the GFR?
freely filtered at the glomerulus
neither reabsorbed nor secreted by renal tubules
how is acyclovir nephrotoxic?
excreted in urine via glomerular filtration and tubular secretion
when concentration exceeds its solubility, crystallization, crystalluria, and renal tubular damage may result if no adequate hydration
_________ binds to immunophilin FK-506 binding protein (FKBP) in cytoplasm to form complex that binds and inhibits mTOR–> blocks interleukin-2 signal tranduction and prevents cell cycle rogression and lymphocyte proliferation
Sirolimus
__________________ IgA immune complex-mediated vasculitis that generally follows upper respiratory or other minor infection
Henoch-Schonlein purpura
type III hypersensitivity reaction
self-limited and resolves after circulating immune complexes clear
clinical manifestations of Henoch-Schonlein purpura
- palpable purpura
- arthralgias
- abdominal pain, intussusceptions
- renal disease similar to IgA nephropathy (hematuria)
most common systemic vasculitis in children
left 12 rib overlies the parietal pleura ____________ and the kidney___________
medially; laterally
CRAB mneumonic for multiple myeloma’s symptoms
HyperCalcemia
Renal involvment
Anemia
Bone lytic lesions/ Back pain
osteolysis –>hypercalcemia–>negative feedback on PTH–> urinary loss of Ca2+
renal failure–> decreased 1,25-dihydroxyvitamin D–> decreased Ca2+ reabsorption
Monoclonal M protein spikes
symptoms of renal cell carcinoma
hematuria, flank pain, abdominal mass (proximal tubules), ppolycythemia (increased erythropoietin production by tumor), fever, weight loss
Which of the following nephron segments responds to vasopressin by increasing absorption of a specific solute that is important for generating a high medullary concentration gradient?
medullary segment of the collecting duct
medullary interstitium is the region of highest osmolarity in the kidney
__________________ of the kidney contain the most dilute urine while the _______________ will contain the most concentrated urine.
distal tubule; collecting ducts
tubular fluid osmolarity in presence of high ADH
1) proximal tubule= water reabsorbed with electrolytes so isotonic with plasma (300 mOsm/L)
2) descending limb of loop of Henle= free water drawn out of tubules so hypertonic (>300mOsm/L)
3) thin ascending limb of loop of Henle= electrolytes, not water, reabosrbed, so hypotonic (<300 mOsm/L)
4) distal convoluted tubule= impermeable to water so hypotonic, continue to reabsorb solutes (100mOsm/L)
5) collecting duct= water leaves, hypertonic urine (up to 1200 mOsm/L)
most dangerous adverse effect of amphotericin B
nephrotoxicity–> hypokalemia, anemia, hypomagnesemia
drug of choice to treat many systemic mycoses
___________ is a DNA-dependent RNA polymerase that incorporates short RNA primers into replicating DNA
Primase
crucial enzyme for bacterial replication as DNA polymerase cannot initiate DNA synthesis without shor nuclei acid sequence primer
Deposition of ______ within Bowman’s space is pathologic step in crescent formation in rapidly progressive glomerulonephritis
Fibrin
leakage of fibrin into Bowman’s space–> proliferation of parietal cells, monocytes, and macrophages
What is found in immunofluorence and light microscopy of Acute poststreptococcal glomerulonephritis?
IM: granular (“starry sky”) (“lumpy-bumpy”) due to IgG, IgM, and C3 deposition along GBM and mesangium
LM: enlarged glomeruli and hypercellular
what (3) things in urine will promote salt cyrstallization leading to renal calculi (kidney stones)?
increased calcium (hypercalciuria), oxalate (hyperoxaluria), and uric acid (hyperuricosuria)
what are two things that can help prevent renal calculi formation (kidney stones)?
increased urinary citrate concentration and high fluid intake
what medications can help reduce risk of progession of worsening diabetic nephropathy?
ACE inhibitos or angiotensin II receptor blockers
along with glycemic and blood pressure control
how to calculate for the total filtration rate
total filtration rate of substance A= GFR * plasma concentration of substance A
GFR= inulin clearance
Total Filtration Rate of Substance A= (inuline clearance)(plasma concentration of Substance A)
net excretion rate of substance A=(inulin clearance)(plasma concentration of Substance A)- (tubular reabsorption of substance A)
treatment for 21-hydroxylase deficiency
adrenocorticotropic hormone (ACTH)
decrease in cortisol–> increase ACTH–.increase androgen overproduction
In Niemann-Pick disease, _______________ deficiency causes accumulation of lipid ____________
sphingomyelinase; sphingomyelin
clinical features: hepatospenomegaly, neurologic regression, and cherry-red macular spot in infancy
Growth hormone binds to cell surface receptors, leading to intracellular activation of ______________ pathway
JAK-STAT
nonreceptor tyrosine kinase
STAT induced IGF-1 gene transcription
same pathway used with prolactin, immunomodulators (cytokines, IL-2, IL-6,etc), G-CSF, erythropoietin, thrombopoietin
inflammation and accumulation of ____________ increases the volume of the retro-orbital tissues to cause proptosis/ exophthalmos
glycosaminoglycans
treat with high-dose glucocorticoids- their anti-inflammatory effects most helpful
antityroid drugs don’t improve ophthalmopathy
_________________ reduce synthesis of estrogen from androgens, suppressing estrogen levels in postmenopausal women and slowing progression of estrogen-receptor positive tumors
Aromatase inhibitors (eg. anastrozole, letrozole, exemestane)
aromatase needed to aromatize androgens to make estrogens (part of the P450 superfamily)
Multiple endocrine neoplasia type 1 characterized by tumors of __________, ___________, and __________
parathyroid gland, pituitary, and pancreas (“3P’s”)
primary hyperparathyroidism –> hypecalcemia or renal stones
pituitary (prolactinomas)–> bitemporal hemianopia and headache from mass effect
pancreas–> gastrinoma (Zollinger-Ellison syndrome), insulinoma and non-function tumors
Debranching enzyme deficiency (Cori disease)–> accumulation of ___________ wiht abnormally _______ (short or long) outer chains (limit dextrins) due to inability to degrade _______________ branch points
glycogen; short; alpha-1,6-glycosidic
present with hypoglycemia, ketoacidosis, heptomegaly, and muscle weakness and hypotonia
signs of androgenic steroid abuse (cardio, derm, genito, psych, breast, other)
cardio: increased hematocrit, increased LDL, decreased HDL
Derm: acne, hirsutism, male-pattern hair loss
genito: clitoromegaly, oligomenorrhea, testicular atrophy, decreased spermatogenesis
psych: depression, hypomania (female), aggressiveness, mood disorders (males)
breast: atrophy for female, gynecomastia for males
other: deepen voice, premature epiphyseal closure (kids)
21-hydroxylase help convert progesterone or 17-OH progesterone into ____________ and _____________, respectively.
11-Deoxcorticosterone (weak mineralocorticoid); 11-Deoxycortisol
skeletal findings in hyperparathyroidism most commonly involve the ________ bone in the __________ skeleton
cortical (compact); appendicular (pectoral girdle, pelvic girdle, and limbs)
subperiosteal thinning that appears radiologically as subperiosteal erosions in phalanges of hand, granular “salt-and-pepper” skull, and osteolytic cysts in long bones (osteitis fibrosa cystica)
glycogen storage disease type II (__________) caused by deficiency of _______________, an enzyme responsible for breaking down glycogen within acidic environment of lysosomes
Pompe disease; acid alpha-glucosidase (acid maltase)
Findings of Pompe disease (glycogen storage disease type II)
cardiomegaly, hypertrophic cardiomyopathy, hypotonia macroglossia hepatomegaly, exercise intolerance
normal blood glucose levels
muscle biopsy show accumulation of glycogen in lysosomes
why is insulin levels higher with oral glucose compared to IV glucose?
incretins=gastrointestinal hormones produced by gut mucosa that stimulate pancreatic insulin secretion due to sugar-containing meals
in IV glucose adminstration, incretin is absent so less insulin secretion
incretin= such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (GIP)
hereditary orotic aciduria occurs due to a defect in what enzyme?
uridine 5’-monophosphate (UMP) synthase
tumor necrosis factor alpha (TNF-alpha) effects on insulin
TNF-alpha is a proinflammatory cytokine that induces insulin resistance through activation of serine kinases, which then phosphorylate serine residues on the beta subunits of insuline receptor (IR) and insuline receptor substrate 1 (IRS-1)–> inhibits tyrosince phosphorylation of IRS-1 by IR and hinders downstream signaling so resistance to normal actions of insulin
beta subunits of insulin receptors have tyrosine kinases that are activated when insulin attaches to the alpha subunits of the receptor to induce signaling
Testosterone purpose in sexual development
development of internal male genitalia, spermatogenesis, male sexual differentiation at puberty (muscle mass, libido)
estrogen purpose in sexual development
endometrial proliferation, development of ovarian granulosa cells, breast development
5alpha-reductase (what does it do? and describe the 2 types)
converts testosterone to DHT
-2 types: type 1 in postpubescent skin, type 2 in genitals
male fetus with defect in this enzyme–> external genitalia do not develop properly–> male pseudohermaphroditism
Thyroid peroxidase- what does it do?
catalyze oxidation of iodide, iodination of thyroglobulin, and coupling reaction between 2 iodinzed tyrosine residues to make MIT and DIT
symptoms of hereditary orotic aciduria
physical and mental retardation, megaloblastic anemia (elevated mena corpuscular volume, low reticulocyte count), elevated urinary orotic acid
patients have failure to thrive and hyperammonemic encephalopphy due to impaired urea synthesis
diabetes and cholesterol relationship
insulin resistance promote increased VLDL production
diabetics may develop a secondary Type IV or V hyperlipidemia (increased VLDL, chylomicrons) and/or secondary diabetic dyslipidemia with elevated LDL and low HDL
Dihydrotestosteron (DHT) purpose in sexual development
development of external male genitalia, growth of prostate, male-pattern hair growth
-also increases testosterone effects due to high affinity for testosterone receptor
what is hereditary orotic aciduria
rare autosomal recessive disorder of de novo pyrimidine synthesis
xanthelasma
xanthoma found on medial eyelids
xanthoma often associated with hypercholesterolemia
metabolic abnormalities associated with both highly-active antiretroviral therapy (HAART like for HIV) and Cushing’s
insulin resistance, hypertriglyceridedema, and reduced HDL cholesterol level
thiazide diuretics can cause (side effects)
hyperglycemia and hypertriglyceridemia, may have small effect on fat distribution (loop diuretics do not have these effects)
gestational diabetes effect on babies
1) beta cell hyperplasia and hyperinsulinism
2) after delivery, hypoglycemia due to excess insulin without the same amount of glucose as before
common adverse side effect of highly-active antiretroviral therapy (HAART) (for HIV)
medication-induced fat distribution (similar to Cushing’s)- lipoatrophy/lipodistrophy (loss of fat from face, butt, and extremities) and central fat deposition
Proton pump inhibitors side effects:
hypomagnesemia and increased risk of osteoporosis
Sheehan syndrome
ischemic necrosis of pituitary gland
pituitary apoplexy
hemorrage of the pituitary gland, different from Sheehan since that is ischemic necrosis
most prostate cancer are ________________ dependent
*androgen
require androgen deprivation therapy to slow progression and relieve bone pain from bone metastases
dihydrotestosterone (DHT)
converted from testosterone by 5-alpha reductase. so when testosterone drops, so does DHT
subcutaneous lipoatrophy associated with what enzymes (2)
nucleoside reverse transcriptase inhibitors (especially stavudine and zidoudine) and protease inhibitors
chromaffin cells’ roles (in adrenal medulla):
1) modified post-ganglionic sympathetic neurons derived from neural crest
2) stimulated by acetylcholine (released from the pre-ganglionic neurons)
3) secrete catecholamines (80% epinephrine and 20% norepinephrine)
effects of beta-blockers on glucose level
non-selective beta-blockers (e.g. propranolol, timolol, nadolol) inhibit norepinephrine/epinephrine-mediated compensatory reactions to hypoglycemia (cholinergic symptoms are unaffected such as sweating, hunger and paresthesias)
blockade of beta2-adrenergic receptors inhibits hepatic gluconeogenesis and peripheral glycogenolysis and lypolysis
use beta-blockers with caution in diabetic patients due to increased risk of hypoglycemia
epinephrine effects on glucose use
limits glucose use, also stimulates hepatic glycogenolysis and gluconeogenesis
what is leuprolide? how does leuprolide treat prostate cancer
- gonadotrophin-releasing hormone analog
- when deliverd in pulsatile fashion, can cause transient rise in LH and tesosterone production (agonist properties)
- continuous GnR stimulation–> supresses pituitary LH release and leads to reduced production of testosterone by Leydig cells (antagonist properties)
amiodarone- what and its side effects
class II anti-arrythmic agent used to suppress life-threatening rhythm disturbances
40% iodine by weight so can alter thyroid function –> cause hypothyroidism
signs of phenylketonuria (PKU)
intellectual disability, gait or posture abnormality, eczema, and musty body odor
hypopigmentation of skin, hair, eyes, and catecholaminergic brain nuclei
(autosomal recessive)
MEN type 2 is associated with germ line mutations in the RET proto-oncogenes and is characterized by what disorders
- pheochromocytomas
- medullarythyroid cancer (malignancy of parafollicular C cells)
- either parathyroid hyperplasia (MEN 2A) or mucosal neuromas and marfanoid habitus (MEN 2B)
T3 vs. T4 in negative feedback on TSH
T3 is the mainly one to have negative feedback
absorption of Ca and phosphate in vitamin D deficiency
Ca and phosphate both decreased–> increaed PTH
Meningoccocal septicemia can cause bilateral hemorrhagic infarction of the:
adrenal gland–> acute adrenal crisis (Waterhouse-Friderichsen syndrome)
structures arising from neural crest cells: MOTEL PASS
Melanocytes, Odontoblasts, Tracheal cartilage, Enterochromaffin cells, Laryngeal cartilage, Parafollicular cells of the thyroid, Adrenal medulla and all ganglia, Schwann cells and Spiral membrane
ions/electrolytes imbalances caused by primary hyperaldosteronism
increased aldosterone–> decreased K+ and H+, increased Na+ (Na+ does not increase above normal range)
H+ decrease–> metabolic alkalosis (bicarb will increase to compensate)
impaired metabolism of 11-deoxycorticosterone (leading to congenital adrenal hyperplasia)- clinical findings
increased production of adrenal androgens so have females with ambiguous genitalia
weak mineralocorticoid accumulate–> development of low-renin hypertension and hypokalemia even when aldosteron synthesis is impaired
different form 21-hydroxylase deficiency since you don’t have hypertension at all
5alpha-reductase deficiency effects
needed for conversion of testosterone to dihydrotestosterone so if deficient, will cause ambiguous genitalia in males not females
What injury will lead to permanent and transient central diabetes insipidus, respectively?
- can be permenant if injury to hypothalamic nuclei
- transient if injury to posterior pituitary/ infundibular
Where does ADH production occur? (2 locations)
occurs in the paraventricular and supranuclei of the hypothalamus
exophthalmos of Graves’ disease caused by
lymphocytic infilitration, enlargment of the extraocular muscles from myositis, fibroblast proliferation, and overproduction of mucupolysaccharides in response to anti-thyroid antibodies
not adrenergic so don’t respond to beta blocker
FSH and what does it do/produce
for male
stimulates the release of inhibin B from the Sertoli cells in the seminiferous tubules of the testicles
produce androgen-binding protein locally, within the seminiferous tubules (responsible for high local testosterone concentration)
what is needed for spermatogenesis?
high local levels of testosterone and FSH
-defective FSH receptors will prevent spermatogenesis and cause low inhibin B levels
SIADH and relationship with Na+
hyponatremia (so no overload)
increased ADH–> excessive water reabsorption–> hypervolemia
–> supresses renin-aldosterone axis–> stimulates production of natriuretic peptides–> excretion of Na+ in urine (natriuresis)
–> patients have normal extracellular fluid volue and low pasma osmolaliy (euvolemic hyponatremia)
SIADH is associated to which cancer?
SIADH caused by small cell carcinoma of the lung
Hormone-sensitive lipase (HSL)
- enzyme found in adipose tissue that catalyzes athe mobilization of stored triglyercides into free fatty acids (lead to ketone bodies) and glycerol (lead to glucose)
- activated by stress hormones (catecholamines, glucagon, ACTH)
- inhibited by insulin
enzyme used to convert T4 to T3
iodothyronine deiodinase aka 5’-deiodinase
Pheochromocytomas
catecholamine-secreting tumors arising from the chromaffin cells of the adrenal medulla or extra-adrenal sympathetic chain
symptoms of Meckel diverticulum
spontaneous but painless lower GI bleeding
potential lead point for intussusceptioin–> collicky ab pain and “currant jelly” (strawberry jam appearance) stools
hyperthyroidism and beta-adrenergic receptors
hyperthyroidism is associated with increased expression of beta-adrenergic receptors
–> hypertension, tachycardia, heat involerance, weight loss, and hyperreflexia
nerve at risk of injury during thyroidectomy
external branch of superior laryngeal nerve—> innervate cricothyroid muscle (tense vocal cords, so damage leads to low, hoarse voice with limited pitch range)
what is Reverse T3
inactive, formed mostly from the conversion of T4 in the periphery
what does fructose 2,6-bisphosphate do?
- balance between gluconeogenesis and glycolysis
- activates phosphofructokinase-1 (PFK-1) to convert fructose 6-phosphate to fructose 1,6-bisphosphate
- inhibit gluconeogenesis, leading to decreased conversion of alanine and other gluconeogeneic substrates to glucose`
how does chronically elevated free fatty acid levels contribute to insulin resistance?
impairing insulin-dependent glucose uptake and increasing hepatic gluconeogenesis
bile acid-binding resins- what do they do and side effect?
inhibit enterohepatic circulation of bile acids–> synthesis of new bile acids and increase uptake of cholesterol to reduce LDL
side effect: hypertriglyceridemia
anterograde axonal transport ( away from nucleus, down axon, toward nerve terminal) mediated by what protein?
kinesin
retrograde axonal transport mediated by dynein
tetrodotoxin poisoning-source and how?
from pufferfish
toxin binds to voltage-gated Na channels in nerve/cardiac tissue–> prevent Na influx and depolarization
symptoms of tetrodotoxin poisoning
dizziness, weakness, loss of reflexes, paresthesias of face and extremities, nausea, vomiting, diarrhea, hypotension, respiratory failure
treat with gut lavage and charcoal
solubility of drug in the peripheral tissues
if tissue solubility is high: large amount of drug taken up from arterial blood, so low venous concentration–> saturation of blood needs more of the drug to become saturated so take longer for the onset of actions (want blood to be saturated for drug to work)
deficiency of ______________ results in recurrent infections by Neisseria species
complement factors that form the membrane attack complex (ie., C5b-C9)
general sensory innervation of the tongue:
1) anterior 2/3
2) posterior 2/3
3) posterior area of the tongue root
1) mandibular branch of trigeminal nerve
2) glossopharyngeal nerve
3) vagus nerve
gustatory innervation (taste buds) of tongue
1) anterior 2/3
2) posterior 2/3
3) posterior area of tongue root and taste buds of larynx an upper esophagus
1) chorda tympani branch of facial nerve
2) glossopharyngeal
3) vagus
clinical features of fragile X syndrome
long, narrow face, prominent forehead and chin, large testes, hyperlaxity of hang joints, developmental delay
how does muscarinic3 receptors promoting synthesis of nitric oxide lead to vasodilation?
NO diffuses to vascular smooth muscle cells to activate guanylate cyclase and increase intracellular cGMP to activate myosin light chain
functions of peroxisomes
- oxidation of very long and branched-chain fatty acids
- hydrogen peroxide degradation
3 D’s of pellagra for niacin deficiency
dementia, dermatitis, diarrhea
symptoms of Vitamin A toxicity:
- acute
- chronic
- tertogenic
- acute: nausea, vomiting, vertigo, blurred vision
- chronic: alopecia, dry skin, hyperlipidemia, hepatotoxicity, hepatosplenomegaly, visual difficulties
- tertogenic: microcephaly, cardiac anomalies, and fetal death
myasthenia gravis- mechanism of action
does compound muscle action improve with stimulation?
autoimmune attack against postsynaptic nicotinic receptors
compound muscle action does not improve with stimulation
Lambert-Eaton myasthenia syndrome- mechanism of action
does compound muscle action improve with stimulation?
autoantibodies against presynaptic voltage-gated calcium channels
compound muscle action does improve with stimulation
Clostridium botulinum toxin- mechanism of action
inhibits acetylcholine release from presynaptic nerve terminals at NMJ
with decreased compound muscle action potential, but increase with repetitive nerve stimulation
minimal alveolar concentration- what is it used to measure and what affects it?
=intrinsic property of anesthetics, percentage of anesthetic in the inspired gas mixture that renders 50% of patients unresponsive
does not depend on type of surgery, duration of anesthesia, or sex, height, and weight
depend on body temp and decreases with increasing age
cryptococcus neoformans- histology, from what, who does it affect, and how is it transmitted?
spherical yeast forms with peripheral clearing and thick capsules; from soil and bird droppings
immunocompromised; respiratory tract
essential tremor- classic signs
- familial tremor
- tremor worsens while maintaining a particular posture
- usually report that symptoms improve with alcohol consumption
treatment for essential tremor
propranolol- nonselective beta-adrenergic antagonist
what is the mechanism of action of triptans?
serotonin 5-HT1B/5-HT1D agonist- inhibit release of vasoactive peptides, promoting vasoconstriction, and blocking pain pathways in the brainstem
for migraines prophylaxis
key features of somatic symptom disorder
excessive anxiety and preoccupation with >/= 1 unexplained symptoms
key features of conversion disorder (functional neurologic symptom disorder)
neurologic symptom incompatible with any known neurologic disease; often acute onset associated with stress
what is neurofibromatosis type I (von Recklinghause disease)
autosomal dominant neurocutaneous disorder due to mutations in NF1 tumor suppressor gene
hyperpigmented macules (cafe-au-lait spots_ over trunk after birth and increased risk of developing CNS neoplasms –> elevated intracranial pressure and headache
mneumonic for eye muscle innervation
LR6-SO4-R3
Oculomotoer nerve (CNIII) palsy- clinical features
-“down and out” due to unopposed action of the superior oblique and lateral rectus
-ptosis
-impaired pupillary constriction and accomodation
diagonal diplopia
principal site for norepinephrine synthesis in brain
what does it control?
locus ceruleus (paired pigmented brainstem nucleus located in the posterior rostral pons near the lateral floor of the fourth ventricle)
control of mood, arousal, sleep-wake states, cognition, and autonomic function (ie blood pressure)
4-drug combination to treat pulmonary tuberculosis
RIPE therapy
rifamycin (eg, rifampin, rifabutin), isoniazid, pyrazinamide, and ethambutol
side effect of rifamycin
GI side effects, hepatotoxicity, minor drug reaction (increase in cytochrome P450), harmless red-orange discoloration of body fluids
mechanism of action: inhibit DNA-dependent RNA polymerase- prevent transcription and lead to deficiency of proteins necessary for mycobacterial survival
mechanism of action of rifamycin
inhibit DNA-dependent RNA polymerase to prevent transcription and lead to deficiency of proteins necessary for mycobacterial survival
structural alteration of this DNA-dependent RNA polymerase induces bacterial resistance
mechanism of bacterial resistance to penicillin
upregulation of beta-lactamase synthesis
resistance to beta-lactam drugs like penicillin, aminopenicillin, cephalosporins, and monobactams
what type of food can cause Hepatitis A
contaminated water or food, with raw or steamed shellfish being the typical
transmission through fecal-oral route
what chemokine receptor allows HIV virus to enter cells
CCR5- act as as a coreceptor to CD4 proteins since HIV virus uses CD4 as the primary receptor. HIV binds to both to enter cell
if cells don’t have CCR5 protein on membrane, then the virus binds to CD4 but cannot enter cell
1) in what cell types are cholesterol converted to androgens in females?
2) where are androgens converted to estrogen?
1) theca interna (synthesis of androgens) (need LH input)
2) granulosa cells (contain aromatase) (need FSH input)
what do interleukin-8 do?
chemokine produced by macrophages that induces chemotaxis and phagocytosis in neutrophils–>becomes pus
calls in the neutrophil to site of infection and then kills then after they arrived and di dtheir jobs
clinical presentationof bacterial vaginosis
grayish-white, “fishy-smelling”, and mildly pruritic vaginal discharge
clue cells (epithelial cells covered with gram-variable rods)
caused by imbalance of vaginal bacterial flors–> overgrowth of Gardnerella vaginalis
what landmarks will help distinguish between direct and indirect inguinal hernias?
inferior epigastric vessels
inguinal hernias different from femoral hernia since they are located above the inguinal ligament
superior mesenteric vessels lie _____________ to the third part of the dudenum
anterior
presence of ca central vascular catheter and receipt of parenteral nutrition are risk factors for
candidemia (Candida in the bloodstream)
Candida display a morphology of branching pseudohyphae with blastoconidia
antigen attaches to ______________ on immunoglobin G1
Fab
phagocytic cells attaches to ______________ on immunoglobin G1
Fc Receptor
histology of cavernous hemangioma
carvernous, blood-filled vascular sapces of variable size lined by a single epithelial layer
biopsy not advisable since it can cause fatal hemorrhage
cavernous hemangioma= most common benign liver tumor
effect of fibrates on gallbladder
reduce cholesterol solubility and promote gallstone formation by reducing bile acid synthesis
effects of pernicious anemia with loss of parietal cell mass
- decreased HCl secretion–> elevated intraluminal pH that leads to upregulation of gastrin secretion
- decreased intrinsic factor secretion so develop vitamin B12 deficiency
4 main classes of antifungal medications and their mechanism of action
1) polyenes (amphotericin B, nystatin): bind to ergosterol molecules in fungal cell membranes to create pores for cell lysis
2) triazoles (ketoconazole, fluconazole, etc): inhibit synthesis of ergosterol
3) echinocandins (caspofungin, micafungin): inhibit synthesis of glucan, a component of fungal cell wall
4) pyrimidines: flucytosine, only agent in this class, is converted to 5-fluorouracil within the cell and interferes with fungal RNA and protein synthesis
____________ virus is a replication-defective RNA virus that is only capable of causing infection when encapsulated with HBsAg
Hepatitis D…aka delta agent or hepatitis delta virus
intestinal atresias of the midgut (eg, jejunum, ileum, proximal colon) are the result of ____________ in utero
vascular occlusion
clinical features of herpes simplex virus type 1 encephalitis
edema and hemorrhagic necrosis of the temporal lobe
headache, fever, mental status changes, cranial nerve deficits, seizures
mechanism of action of isoniazid
antimicrobial agent active only against mycobacteria
inhibition of mycolic acid synthesis, so mycobacteria lose their acid-fastness and become unable to synthesize new cell walls or multiply
in what gastric layers do parietal cells reside?
upper glandular layer
they secrete gastric acid and intrinsic factor
laboratory/imagining studies findings of rheumatoid arthritis
- positive rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies
- C-reactive protein and ESR correlate with disease activity
- X-ray: soft tissue swelling, joint space narrowing, bony erosions
Meckel’s diverticulum is a true diverticulum and consists all parts of the intestinal wall, which include:
mucosa, submucosa, and muscularis
false diverticula only have mucosa and submucosa
what are maternal serum alpha-fetoprotein (MSAFP) screening used for?
identify pregnancies at high risk of congenital defects
- open neural tube defects
- ventral wall defects
- multiple gestation
- aneuploidies (when have decreased MSAFP, the others are increased MSAFP)
features of mitochondrial myopathy
mitochondria not functioning properly so can’t make enough ATP–> myopathy, lactic acidosis, nervous system dysfunction
muscle biopsy shows ragged red fibers
inheritance: materal mitochondrial DNA
Staphylococcus virulence mechanism by which it causes disease?
synthesis of an extracellular polysaccharide matrix that encases the bacteria. this biofilm acts as a barrier to antibiotic penetration
mechanism of action for Class III antiarrhythmic drugs (eg, amiodarone, sotalol, dofetilide)
block potassium channels and inhigibt outward potassium currents during phase 3 of cardiac action potential –> prolong repolarization and total action potential duration
___________ has been the leading cause of cancer mortality in both women and men in the United States since the 1980s
lung cancer
how does the metyrapone stimulation test work? what is it testing for?
sensitive indicator of hypothalamic-pituitary-adrenal axis integrity
blocks cortisol synthesis by inhibiting 11-beta-hydroxylase so no negative feedback from cortisol on pituitary–> increase in ACTH
what is primary and secondary hyperaldosteronism
primary: increased aldosterone, decreased renin- due to aldosterone-producing tumor or bilateral adrenal hyperplasia
secondary: increased both renin and aldosterone- due to renovascular hypertension, renin-secreting tumor, and edema
clinical features of arginase deficiency
- an enzyme in urea cycle that produces urea and ornithine
- diagnosed based on elevated arginine levels
- spastic diplegia (stiffness of lower extremities)
- abnormal movments
- growth delay
- treat with low-protein diet devoid of arginine
clinical features of Lesch-Nyhan syndrome
X-linked recessive
dystonia, choreoathetosis, self-mutilation, and hyperuricemia
cause of Lesch-Nyhan syndrome
deficiency of hypoxanthine-guanine phosphoribosytransferase (HGPRT)- enzyme for purine salvage pathway
deficiency–> increased degradation of guanine and hypoxanthine bases into uric acid and increased demand for de novo purine synthesis
individuals with Down syndrome have a 10- to 20-fold increased risk of developing ________ and __________ (cancer)
Acute lymphoblastic leukemia and acute myelogenous leukemia
which part of the nephron do potassium sparing diuretics act on?
collecting duct
spironolactone and amiloride
which part of the nephron do carbonic anhydrase act on
proximal tubule (acetazolamide)
osmotic diuretics act on this part of the nephron
descending limb of Henle’s loop and proximal tubule (mannitol)
loop diuretics act on this part of the nephron
thick ascending limb of Henle’s loop
furosemide
thiazide diuretics act on which part of the nephron
distal convoluted tubules
hydrochlorothiazide
Guillain-Barre syndrome can be caused by _______________ infection
Campylobacter jejuni
what is hereditary angioedema?
inherited autosomal dominant condition that causes episodes of painless, non-pitting, well-circumscribed edema. If it affects the tracheobronchial tree, then cause respiratory obstruction
indicated by low serum levels of C1 esterase inhibitor
lab findings of hereditary angioedema
low serum levels of C1 esterase inhibitor, increased level of active kallikrein and bradykinin
contraindicated for ACE inhibitors since ACE inhibitors can increase bradykinin even more
how does lithium induce nephrogenic diabetes insipidus?
reduce ability of the kidney to concentrate urine primarily by antagonizing the action of vasopressin (antidiuretic hormone) i the collecting tubules and ducts
what is X-linked agammoglobulinemia (XLA)?
mutation in the Bruton tyrosine kinase gene causes failure of bone marrow pre-B cells (CD19+, CD20+) to develop into mature, circulating B lymphocytes (CD19+, CD20+, CD21+)
have low or absent B cells in peripheral blood and pan-hypogammaglobulinemia ( low immunoglobulin)
embryologic derivatives: mesoderm
muscles (skeletal, cardiac and smooth), connective tissue, bone, cartilage, serosa linings (eg peritoneum), cardio system, blood, lymphatic system, spleen, internal genitalia, kidney and ureters, adrenal cortex
embryologic derivatives: endoderm
GI tract, liver, pancreas, lungs, thymus, parathyroids, thyroid follicular cells, middle ear, bladder and uretra
embryologic derivatives: ectoderm- surface ectoderm
Rathke pouch (anterior pituitary, lengs and cornea, inter ear sensory organs, olfactory epithelium, nasal and oral epithelial linings, epidermis; salivary, sweat and mammary glands
embryologic derivatives: ectoderm-neural tube
brain and spinal cord, posterior pituitary, pineal gland, retina
embryologic derivatives: ectoderm- neural crest
autonomic, sensory and celiac ganglia; Schwann cells; pia and arachnoid mater; aorticopulmonary septum and endocardial cushions; branchial arches (bones and cartilage); skull bones, melanocytes; adrenal medualla
risk of asbestos exposure
asbestosis, pleural plagues, bronchogenic carcinoma, and malignant mesothelioma
Bronchogenic carcinoma is the most common malignancy then mesothelioma
clinical features of DiGeorge syndrome
- conotruncal cardiact defects (tetrology of Fallot, truncus arteriosus, interrupted aortic arch)
- abnormal facies
- thymic hypoplasia/aplasia (T-cell deficiency)
- craniofacial deformities (cleft palate)
- hypocalcemia/hypoparathyroidism
4 criteria of tetrology of Fallot
1) pulmonary infundibular stenosis (most important determinant for prognosis)
2) right ventricular hypertrophy
3) overriding aorta
4) ventricular septal defect
graft-versus-host disease- cause
for those who are immunocompromised, immunocompetent donor T cells from the graft survive and migrate into host tissues–> recognize host MHC antigens as foreign and become sensitized
donor CD4+ and CD8+ T cells (not B cells) participate in host cell destruction\
GVDH occur after transplantation of organs rich in lymphocytes (eg, liver)
carbonic anhydrase inhibitor diuretic- mechanism of action
block bicarb reabsorption so enhanced bicarb and water excretion–> increase urinary pH and potential metabolic acidosis
also used to help with intraocular pressures in open-angle and angle-closure glaucoma
lesion of the _________________ can produce contralateral homonymous hemianopia with macular sparing
occipital cortex (eg, posterior cerebral artery occlusion)
best an most reliable auscultatory indicator of the degree of mitral stenois is the __________ interval
A2-OS (A2-aortic valve closure) (opening snap due to abrupt tensing of the value leaflets as the mitral valve reaches its maximum diameter during forceful opening)
shorter interval= more severe stenosis
can also hear diastolic rumbling murmur with presystolic accentuation due to left-atrial contraction
dengue hemorrhagic fever- symptoms
high-grade fever, diffuse macular rash, muscle and join pain, leukopenia, hrombocytopenia, elevated liver enzymes, headache, retro-orbital pain, bleeding
primary vs secondary infection of Dengue virus
primary- can be asymptomatic or self-limited disease in most adults
secondary- infection with a different viral serotype and usually causes more severe illness
O2 and CO2 content of arterial vs. venous blood during exercise
homeostatic mechanism maintain arterial O2 and CO2 contents and pH near normal resting values
venous blood O2 and CO2 and pH changes- O2 decreased and CO2 increased, pH decreased
what is case-control stdy
selecting patients with particular diseases (cases) and without that disease (controls) and determining their previous exposure status
cross-sectional study aka __________
prevalence study= simultaneous measurement of exposure and outcome
surface marker of monocyte-macrophage cell lineage
CD14
histology signs of secondary tuberculosis
caseating granulomas with central necrosis and Langhans giant cells
posteromedial papillary muscle is supplied solely by the _______________ artery
posterior descending
anteroateral papillary muscle has dual blood supply from the _______________ and ____________ arteries
left anterior descending (LAD) ; left circumflex
clinical features of coarctation of the aorta
systolic hypertension of upper extremities along with characteristic diminished and /or delayed femoral pulses (brachial-femoral delay) (femoral
clinical presentation of aortic regurgitation
increase in LV end-diastolic volume and wall stress, hypertrophy of LV, diastolic decresendo murmur at left sternal border in 3rd and 4th intercostal space, wide pulse pressure (bounding femoral and carotid pulses), head bobbing
frothy, foamy urine may be caused by _____________ or __________ in the urine
proteinuria; bile salts
can lead to regional or generalized interstitial edema because the decrease in serum albumin and total protein lowers the plasma oncotic pressure and increases net plasma filtration in capillary beds (associated with nephrotic syndrome)
_______________ is the only prokaryotic polymerase that also has 5’ to 3’ exonuclease activity
DNA polymerase I
functions to remove the RNA primer created by RNA primase to be replaced with DNA and repair damaged DNA sequences
function of topoisomerase II aka DNA gyrase in prokaryotes
relieve tension created during DNA strand unwinding by adding or removing supercoils into the circular DNA
antibiotics that work by inhibiting DNA gyrase: fluoroquinolones
what does DNA polymerase III do?
Prokaryotes only. Elongates leading strand
by adding deoxynucleotides to the 3′ end. Elongates lagging strand until it reaches primer of preceding fragment. 3′ –>5′ exonuclease activity “proofreads” each added nucleotide.
DNA polymerase III has 5′ 3′ synthesis and proofreads with 3′ 5′ exonuclease.
What cell types are directly responsible for synthesizing fibrous cap of atheromas in atherosclerosis
vascular smooth muscle cells
homeobox or hox gene code for ______________ that bind to regulatory regions on DNA, altering the expression of genes involved int eh segmental organization of the embryo
transcription factors
homeobox gene mutations–> abnormalities such as skeletal malformation and improperly positioned limbs and appendages
locations to auscultate for holosystolic murmurs
1) mitral regurgitation
2) tricuspid regurgitation
3) ventricular septal defect
best heard at:
1) apex
2) left 2nd and 3rd intercostal spaces
3) left 3rd and 4th intercostal spaces
S1 heart sounds
mitral and tricuspid valve closure. Loudest
at mitral area.
S2 heart sounds
aortic and pulmonary valve closure.
Loudest at left upper sternal border.
S3 heart sounds
in early diastole during rapid ventricular filling phase. Associated with increased filling pressures (eg, mitral regurgitation, HF) and more common in dilated ventricles (but can be normal in children and young adults).
S4 heart sounds
in late diastole (“atrial kick”). Best heard at apex with patient in left lateral decubitus position. High atrial pressure. Associated with ventricular noncompliance (eg, hypertrophy). Left atrium must push against stiff LV wall. Consider abnormal, regardless of patient age.
characteristics of Pseudomonas aeruginosa
motile gram-negative rod that is oxidase-positive, produces green pigment during culture (aerugula is green)
“hot tub folliculitis” is due to _________________ infection of the hair follicles following exposure to a pool or spa not maintained appropriately
Pseudomonas aeruginosa
first line agent to treat narcolepsy because it is effective, well tolerated, and drug abuse is rare (non-amphetamine stimulant)
Modafinil–enhance dopaminergic signaling
why is COX 2 inhibitors preferred over COX1 inhibitors when deciding NSAIDs?
COX2 inhibitors have less risk of bleeding and gastrointestinal ulceration
Function of type II pneumocytes
source of pulmonary surfactant and have the ability to proliferate in response to injury
act as progenitor cells for type I pneumocytes, which cannot regenerate on their own
structure of MHC class I that present antigen to CD8+ cytotoxic T-cells
heavy chain and beta2-microglobulin
structure of MHC class I that present antigen to CD4+ T-helper lymphocytes
alpha and beta polypeptide chains
_________ is a cause of rapidly progressive (crescentic) glomerulonephritis type 3 (pauci-immune)
Granulomatosis with polyangiitis (Wegener’s)
Granulomatosis with polyangiitis (Wegener’s): characteristic findings:
1) lowr respiratory tract- pulmonary symptoms (cough and/or hemoptysis)
2) involvement of the upper respiratory tract (i.e., ear , nose, sinuses, throat)
3) renal disease in the form of rapidly progressive (crescentic) glomerulonephritis
embryonic development of the urachus
In the 3rd week the yolk sac forms the allantois, which extends into urogenital sinus. Allantois becomes the urachus, a duct between fetal bladder and umbilicus.
patent urachus that connects the umbilicus and bladder to due to:
complete failure of obliteration of the urachus… aka persistence of allantois remnant
patients present with straw-colored urine discharge from the umbilicus
what is Gerstmann syndrome?
neurologic disorder characterized by:
1) agraphia
2) acalculia (can’t carry out math problems)
3) finger gnosia (can’t identify individual fingers)
4) left-right disorientation
due to damage to the angular gyrus of the dominant parietal lobe
Hemoglobin C is caused by a _____________ mutation that results in a ______________ residue being substituted by ______ in the beta globin chain
missense; glutamate; lysine
most common eye-related complication of congenital cytomegalovirus infection
chorioretinitis
earliest lesions of atherosclerosis and can be seen as early as the second decade of life
fatty streaks
appear as a collection of lipid-laden macrophages (foam cells) in the intima that can eventurally progress to atherosclerotic plaques
personality disorder- schizoid
prefers to be a loner, detached, unemotional
cluster A- weird
personality disorder-schizotypal
eccentric; odd thoughts, perceptions and behavior
=magical thinking
cluster A-weird
personalitydisorder: histrionic
dramatic, superficial, attention-seeking, sexually provocative
cluster B-wild
influenze epidemics and pandemics are typically caused by reassortment of the ____ segments coding for ________________ or __________ proteins (major antigenic shifts)
RNA; hemagglutinin; neuraminidase
________ is a cause of acute, painless, monocular vision loss–> caused by thromboembolic complications of atherosclerosis from the _______________ artery and through the ______ artery
Retinal arter occlusion; internal carotid; ophthalmic
blood flow is ______ proportional to the vessel radius raised to the _____ power
directly ; fourth
*resistance to blood flow is inversely proportional to the vessel radius raised to the fourth power
test used for diagnosis of Cryptococcus neoformans meningoencephalitis in HIV (+) poatients
latex agglutination test detects the polysaccharide capsule antigen
india ink staining of theCSF shows round or oval budding yeast
_________ is the major amino acid responsible for transferring nitrogen to the liver for disposal
alanine
how does alanine and glutamine play a role in transporting nitrogen throughout the body
catabolism of proteins–> release of alanine and its amino groups transferred to alpha-ketoglutarate to form glutamate–> glutamate processed in liver to form urea to be disposed
characteristics of amiodarone (how it works)
-class III antiarrhythmic drug for management of a variety of supraventricular and ventricular arrhythmias block K+ channels and inhibit outward K+ currents during phase 3 to prolong repolarization and total action potential duration -QT prolongation -very little risk of inducing torsades de pointes
local cutaneous adverse effects of chronic topical corticosteroid administration
atrophy/thinning of the dermis that is associated with loss of dermal collagen, drying, cracking, and/or tightening of the skin, telangiectasias (spider veins), and ecchymoses (discoloration of skin resulting from bleeding underneath, typically caused by bruising)
niacin as treatment of _______________
hyperlipidemia
- increases HDL
- decreases LDL and tryglycerides
- causes cutaneous flushing mediated by prostaglandins
ECG findings of atrial fibrillation
absence of P waves and irregularly irregular rhythm with varying R-R intervals
some have irregular, low-amplitude, fine fibrillatory waves (f waves) between QRS complexes for the chaotic atrial activation
measure urinary concentration of _____________ can screen for early-stage diabetic nephropathy
albumin
which diuretics are used to treat patients with heart failure exacerbation and significant fluid overload (eg, pulmonary and/or peripheral edema)?
WHY?
loop diuretics (IV)
most potent type of diuretics and provide maximum amount of diuresis in the shortest period of time
when to use carbonic anhydrase inhibitors (acetazolamide)? and WHY?
weak diretics so used to treat glaucoma and acute mountain sickness
mechanism of loop diuretics (furosemide, torsemide, bumetanide)
and where in the nephron?
inhibit Na-K-2Cl symporter in thick ascending limb of loop of Henle
blocks Na+ and Cl- reabsorption so increase excretion of Na+, Cl- and water
can Enterococcus convert nitrates to nitrites
no- so would find negative result on urinalysis nitrite
immfluorescent microscopy findings for Pauci-immune rapidly proliferative glomerulonephritis
no immunoglobulin or complement deposits on the basement membrane
what is a key finding with Pauci-immune rapidly proliferative glomerulonephritis
antineutrophil cytoplasmic antibodies (ANCA) in their serum
condition associted with granulomatosis with polyangiitis (Wegener) or microscopic polyangiitis but can be idiopathic
what stimulate eosinophils for parasitic defense?
IL-5 produced by TH2 and mast cells
eosinophils, macrophages, neutrophils, and natural killer cells
mechanism of action
antibody-dependent cell-mediated cytotoxiity
cause of stress incontinence (leakage with coughing, lifting, sneezing
decrease urethral sphincter tone and urethral hypermobility
bladder emptying is mainly due to ______________, while continence is maintained by the _______________
detrusor muscle contraction; urethral sphincters
what is overflow incontinence?
what is it caused by?
incomplete emptying and persistent involuntary dribbling
impaired detrusor contractility; bladder outlet obstruction
relationship between H2PO4- and NH4+ with diabetic ketoacidosis
these two are acid buffers for the urine–> they take up H+ to get rid of H+ without lowering urinary pH
both increased with DKA
characteristics of Fabry disease (not the symptoms)
- X-linked recessive lipid storage disorder
* alpha-galactosidase A deficiency–>can’t break down globotriaosylceramide (Gb3), sphingolipid
symptoms of Fabry
- neuropathic pain and hypohidrosis (decreased sweating)
- distal extremity pain and burning and distal loss of hot/cold temp sensation
- worse with exercise, stress, and fatigue
- angiokeratomas (dark red, non-blanching macules and papules around but, groin, and umbilicus)
- telangietasias (spider veins)
- cerebrovascular, cardiac, and glomerular complications
principal site of uric acid precipitation and why
collecting ducts due to low urine pH
how to differentiate between metabolic and respiratory alkalosis
pCO2
high–> metabolic
low–> respiratory
features of thiazide or loop diuretic induced metabolic alkalosis
- high arterial blood pH, HCO3-, pCO2, Na+
- decrease K+ and H+ and Cl-
- can be correct by volume and NaCL repletion with isotonic saline (saline-responsive)
features of mineralocorticoid excess state induced metabolic alkalosis
- increase Na+, HCO3-, CL-
- decrease K+ and H+
- cannot be corrected by isotonic saline due to persistent mineralocorticoid activity (saline-unresponsive)
electrolyte abnormalities associated with loop diuretic
hypokalemia, metabolic alkalosis, hypocalcemia
(in serum)
(thick ascending limb of loop of Henle)
electrolyte abnormalities associated with thiazide diuretics
hyponatremia hypokalemia metabolic alkalosis hypercalcemia (in serum)
(distal convoluted tubule)
electrolyte abnormalities associated with carbonic anhydrase
hypokalemia
metabolic acidosis
(in serum)
(proximal tubule)
electrolyte abnormalities associated wtih sodium channel blockers and mineralocorticoid receptor antagonists (diuretics)
hyperkalemia
metabolic acidosis
(in serum)
(cortical collecting duct; cortical collecting tubules)
diuretics used to help decrease risk for calcium kidney stone
thiazides–> decrease urine Ca2+ excretion
loop diuretics stimulate _____________ release to increase renal blood flow to increase GFR
prostaglandin
what glomerular disease has glomerular basement membrane disruptions and fibrin deposition on electron microscopy
Goodpasture
GBM breaks are due to fibrinoid necrosis of the glomeruli
crescent formation contributed by fibrin escape into Bowman’s space
blood supply to the proximal ureter comes from branches of the _______ artery; distal ureter is supplied by ____________
renal artery; superior vesical artery
highest osmolarity occurs at the ________________ of the nephron
loop of Henle
severe toxicities of aggressive osmotic diuretics such as mannitol
pulmonary edema and dehydration
increased Ca2+ will _______ PTH, but decreased Ca2+ will _______________ PTH
suppress; increase
relationship between chronic kidney disease and serum calcium level
chronic kidney dz–> hyperphosphatemia (binds serum Ca2+) and low 1,25-dihydroxyvitamin D (decrease intestinal Ca2+ absorption and Ca2+ release from bone)–> hypocalcemia–> increase PTH–> secondary hyperparathyroidism
low oncotic pressure in nephrotic syndrome such as minimal change disease can lead to
increased lipoprotein production in the liver
what would you see with the electron microscopy for diabetic nephropathy?
hyaline, acellular deposits composed of plasma proteins, can be seen in Kimmelstiel Wilson nodules
every time GFR ________, creatinine levels ________
halves; doubles
RPF is calculated using the clearance of __________________
para-aminohippuric acid (PAH)
RPF= PAH clearance= (urine [PAH] X urine flow rate/ plasma [PAH]
RBF=(PAH clearance)/ (1-hematocrit)
what type of renal complications happen in multiple myeloma
myeloma case nephropathy due to excess excretion of free light chains (Bence Jones proteins)–> form cases that cause tubular obstructiona nd epithelial injury (glassy casts stain intensely eosinophilic)
suspect multiple myeloma when an elderly patient present with these 5 things
1) fatigability (due to anemia)
2) constipation (due to hypercalcemia)
3) bone pain, most commonly in the back and ribs (bone lysis due to production of osteoclast-activating factor by myeloma cells)
4) elevated serum protein (monoclonal proteins)
5) renal failure
think CRAB
during the recovery phase (polyuric phase) of acute tubular necrosis, patients can become dehydrated and can develop severe_____________
hypokalemia
-due to high volume, hypotonic urine
common side-effects of ACE-inhibitors
decreased GFR, hyperkalemia, and cough
angioedema=rate, but life-threatening
ureters pass ______________ to the ovarian (gonadal) vessels with the retropreritoneum and ______ to the common/external iliac arteries to reach the true pelvis
posterior (water under the bride)
anterior
equation for net filtration pressure
=(hydrostatic pressure in capillaries- hydrostatic presure in interstitium) - (oncotic pressure of capillaries- oncotic pressure of interstitium)
characteristics of Foscarnet (antiviral agent)
an analog of pyrophosphate that can chelate calcium and promote nephrotoxic renal magnesium wasting
hypocalcemia and hypomagnesemia–> seizure
most common and second most common places for metastasis of advanced stage renal cell carcinoma
lung and bone
significant renal hypoperfusion–> hyperplasia of __________ cells
JG cells of the afferent arteriole (modified smooth muscle cells with renin-containing zymogen granules)
humoral hypercalcemia of malignancy is caused by secretion of ________________
parathyroid hormone-related protein (PTHrP)
–>increased bone resorption and decreased renal excretion of calcium
grapefruit juice______________ CYP450 3A
inhibit–> increase nephrotoxicity of durgs
diabetic autonomic neuropathy can cause __________ incontinence
overflow–> due to inability to sense a full bladder and incomplete emptying
Beta blockers’s mechanism of action on the RAA system
- decrease RBF
- sympathetic stimulation
- prevent increase of renin to decrease BP
does beta blockers affect bradykinin levels?
no- since they don’t have an effect on ACE activity
host T-lymphocyte sensitization against graft (foreign) MHC antigens mediates ____________ rejection
acute cellular transplant rejection
treatment for acute transplant rejection
- calcineurin inhibitors such as cyclosporin or tacrolimus
* corticosteroids
para-aminohippuric acid has the lowest concentration in the ____________
Bowman’s space
(not reabsorbed by any portion of the nephron)
highest in proximal tubules due to its active secretionandreabsorptionof waterand solutes
metanephric diverticulum (ureteric bud) of the kidney give rise to
collecting system of the kidney: such as the collecting tubules and ducts, major and minor calyces, renal pelvis, and the ureters
metanephric mesoderm (blastema) of the kidney gives rise to
glomeruli, Bowman’s space, proximal tubules, loop of Henle, and distal convoluted tubules
recovery phase of acute tubular necrosis
re-epithelization of tubules
presentation of renal artery stenosis
unilateral kidney atrophy, elderlys due to atherosclerotic changes, women of childbearing age due to fibromuscular dysplaia
have hypertension and abdominal bruit
transitional cell carcinoma of bladder (risk factors)
smokers, individuals with occupational exposure to rubber, plastics, aromatic amine-containing dyes, textiles, or leather, men> women
biochemical risk factors for ____________________ include: low urinary pH and low urine volume with high uric acid concentration, which may occur i setting of chronic diarrhea
uric acid nephrolithiasis (kidney stones)
*diarrhea–>metabolic acidosis–> kidnesy compensate with excreting more H+ and reabsorbing more bicarb–> insoluble uric acid
acute tubular necrosis- histology characteristics
proximal tubular cell ballooning and vacuolar degeneration
presence of oxalate crystals in tubular lumen is highly suggestive of _______________
ethylene glycol poisoning—> lead to calcium oxalate crystals
second most common cause of UTI in sexually active women is
Staphylococcus saprophyticus
characteristic of IgA nephropathy (Berger disease)
*most common cause of glomerulonephritis
* older children and young adults
painless hematuria within 5-7 days of upper respiratory tract infection
characteristics of clear cell carcinoma in histology
rounded/polygonal cells with abundant clear cytoplasm (in proximal tubules)
- contain lots of inracellular glycogen and lipids
- from the proximal tubular epithelial cells
most common form of clear cell carcinoma= renal cell carcinoma
hemolytic uremic syndrome- characterized by a triad of:
microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury
NSAID-associated chronic renal injury is morphologically characterized by
chronic interstitial nephritis papillary necrosis
cystinuria- genetics and cause
autosomal recessive
defective transportation of dibasic amino acids (cystine, ornithine, arginine, and lysine) across intestinal and renal tubular epithelium
–> cystine crystals (hexagonal-shaped)
which diuretics can cause ototoxicity
loop diuretics
inhibiting Na/K/2Cl symporters in ascending limb of the loop of Henle–> may inhibit similar symporters in the inner ear
poor prognostic factor for post-streptococcal glomerulonephritis
increased age, pre-existing kidney disease
for children 5-12yo–> >95% recover
drug induced acute interstitial nephritis- symptoms and signs
fever, maculopapular rash, and symptoms of acute renal failure 1-3 weeks after beginning a beta-lactam antibiotic, peripheral eosinophilia and eosinophiluria
symptoms go away afte cessation of medication
clearance of digoxin
by the kidney
digoxin=cardiac glycoside
digoxin- mechanism of action
cardiac glycoside
Direct inhibition of Na+/K+ ATPase –> indirect inhibition of Na+/Ca2+ exchanger. increase [Ca2+]i –> positive inotropy. Stimulates vagus nerve –> decreased HR.
idiopathic membranous nephropathy is associated with circulating ___ antibodies to the _______________ receptor
IgG4; phospholipase A2
endometrial cells undergo ______________ to have menstrual bleeding
apoptosis
pelvic floor strengthening (Kegel exercises) targets the _____________ (muscle) to improve support around the urethra and bladder (helps with stress urinary incontinence)
levator ani
human chorionic gonadotropic (hCG) is structurally similar to _____
LH
therefore simulates LH surge by inducing ovulation
LH and hCG has similar alpha subunit (structurally similar)
live mass associated with an increased alpha-fetoprotein level is typical presentation of
hepatocellular carcinoma
-hepatocellular carcinoma is strongly associated with HBV infection and is often precded by HBV-induced cirrhosis
breast carcinoma: malignant infiltration of ____________ of the breast causes dimpling of the overlying skin
suspensory ligaments
what structure is the most vulnerable to injury during a hysterectomy?
ureter
protective factors against epithelial ovarian cancer
oral contraceptives, multiparity, and breastfeeding since they decrease the frequency of ovulation
risk factors: BRCA mutation, nulliparity, and infertility
histology of metastatic tumor cells of the ovary from Krukenberg tumor from the stomach
have large amounts of mucin with apically displaced nuclei–> signet ring appearance
characteristic of ductal carcinoma in situ
breast cancer
ducts distended by pleomorphic cells with prominent central necrosis that do not penetrate the basement membrane
- precursor to invasive ductal carcinoma, most common type of breast cancer
- can also lead to Paget disease
mechanism of action for misoprostaol- for terminating pregnancy
misoprostol- prostaglandin E1 agonist==> cervical softening and uterine contractions to expel pregnancy
mechanism of action for mifepristone-> terminate pregnancy
progesterone antagonist and glucocorticoid antagonist
mechanism of action of methotrexate
folic acid antagonist–> decrease DNA synthesis
help with abortion, cancer, rheumatoid arthritis, psoriasis , IBD, vasculitis
characteristic of turner syndrome
narrow, high-arched palate; low hairline; webbed neck’ widely spaced nipples; cubitus valgus; aortic coarctation; bicuspid aortic valve; horseshoe kidney; streak ovaries; amenorrhea; infertility; short stature
in females, ______________________ fuse to form the fallopian tubes, uterus, cervix, and upper vagina
paramesonephric ducts
*incomplete lateral fusion of the ducts–> bicornuate uterus (indentation in the center of the fundus)
detection of ____ and ____ is used for prenatal screening of neural tube defects
alpha-fetoprotein (AFT); acetylcholinesterase
selegiline-mechaism of action
inhibitor of MAO, type B (inhibit breakdown of dopamine)
clinically used to delay progression of Parkinson disease
drug of choice for treating trigeminal neuralgia (pain in the distribution of CN V)
carbamazepine
- make sure to check CBC for aplastic anemia
- a P450 inducer
three important mitochondiral syndromes
1) leber hereditary optic neuropathy–> bilateral vision loss
2) myoclonic epilepsy with ragged-red fibers: myoclonic seizures and myopathy with exercise
3) mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS)
mitochondiral diseases affect males and females with _____ frequencey
equal (100%)
heteroplasmy
demyelination of 1 optic nerve: pupillary reflex?
if light on the side affected: no constriction of either eye. Constriction when light is on the side that is not affected
amino acid precursor for serotonin
tryptophan
amino acid precursor for thyroxine, dopamine, epinephrine, norephinephrine, and melanin
tyrosine
treatment or serotonin syndrome
cyproheptadine (serotonin receptor antagonist)
most common finding with posterior cerebral artery stroke
contralateral homonymous hemaniopsia, often with macular sparing
symptoms of temporal lobe lesion
- disrupt Meyer’s loop and produce contralateral superior quadrantanopia
- aphasia, memory deficits, seizures, and hallucinations
what cause syringomyelia
central cystic dilation in cervical spinal cord (syrinx) that enlarges and damage ventral white commissure and anterior horns
symptoms of syringomyelia
bilateral loss of pain and temp sensation
loss of UE pain and temp, UE weakness and hyporeflexia, LE weakness and hyperreflexia and kyphoscoliosis
facial effect of parotid gland tumor
tumor can compress and disrupt ipsilateral facial nerve and branches –> facial droop
blood discharge from nipples commonly caused by
intraductal papilloma
- due to proliferation of papillary cells in a duct or cyst wall with fibrovascular core and may contain foci of atypia or ductal carinoma in situ
- blood from twisting of the vascular stalk of the papilloma in the duct
what part of the body gets cut in a midline episiotomy
perineal body (fibromuscular tissue between urogenital and anal triangle)
epithelia type of ovary
simple cuboidal
-rapidly proliferate to repair ovulatory surface defects
insulin resistance during pregnancy is due to this hormone
human placental lactogen (hPL) (pepetide hormone secreted by syncytiotrophoblast)
cause of turner syndrome
45, X karyotype due to loss of paternal chromosome X
hypospadia
abnormal opening of penile urethra on ventral surface of penis due to failure of the urethral folds to fuse
(urethral folds in females don’t fuse and form the labia minora)
clinical features of polycystic ovary syndrome
- androgen excess–> hirsutism, acne, androgenic alopecia
- ovarian dysfunction: menstrual irregularity, polycystic ovaries
- insulin resistance
- obesity
- elevated LH
treatment for polycystic ovary syndrome
- weight loss
- combination of hormonal contraceptives
- metformin (for hyperglycemia/diabetes)
mechanism of action of clomiphene
antagonist of estrogen receptors in hypothalamus –> prevents negative feedback inhibition on the hypothalamus and pituitary by circulating estrogen–> increased FSH and LH–> ovulation
(help people with PCOS get pregnant)
cause of ovarian torsion
twisting of the infundibulopelvic ligament due to weight of a large adnexal mass
why use both chloroquine and primaquine for treating malaria?
chloroquine- treatment of choice fo uncomplicated malaria
primaquine` added with infection with P vivax and P ovale to eradicate the intrahepatic stages , which are responsible for relapses of malari
what cause congenital torticollis
malposition of the head in utero or birth trauma
child prefers to hold the head tilted to one side
revolve with conservative therapy and stretching
what is a complete mole pregnancy?
when an empty ovum is fertilized by a haploid sperm. The chromosomes from the sperm duplicate to form 46, XX that only has paternal DNA
what is endometriosis
aka ectopic endometrium
- presence of endometrial tissue outside the uterus
- inflammation after menstruation–> distorts organ structure and function–> infertility
risk factors of endometriosis
nulliparity, early menarche, and prolonged menses
bilateral ligation of ___________ artery can decrease uterine blood flow and control postpartum hemorrhage
internal iliac
dysmorphic features of Down syndrome
epicanthal folds, upslanting palpebral fissures, protruding tongue, excessive skin at the nape of the neck, birthweight and length often below average, hypotonia and weak startle (Moro) reflex
*cardiac defects
_________ due to hypogonadotrophic hypogonadism can be treated by pulsatile administration of GnRH
Anovulation (to treat infertility)
most likely location of the urethra to be associated with pelvic fractures
posterior urethra at the bulbomembranous junction
_______ is needed for normal renal deveopment
Angiotensin II
*so moms can’t take ACE inhibitor during pregnancy–> oligohydraminos and potter sequence
what hormone is elevated in menopausal women?
FSH
*due to lack of inhibition from estrogen
what is neonatal abstinence syndrome (NAS)?
symptoms?
NAS= newborns with mothers who used drug such as opiate during pregancy
crying, tremors, hypertonia, jittery movments, sweating, pupillary dilation, tachypnea, sneezing, irritability, and diarrhea
neuroimagining of a patient iwth herpes simplex virus (HSV) encephalitis
abnormal MRI signal in the bilateral temporal lobes
lymphatic drainage of scrotum occurs via the_________________ lumph nodes
superficial inguinal
*drain nearly all cutaneous lymph from umbilicus to the feet, including external genitalia and anus
lymphatic drainage of the testes, ovaries, kidneys, and uterus drains directly into the __________ lymph nodes
para-aortic (retroperitoneal)
what produces beta-hCG and when?
syncytiotrophoblast secrete it 6-7 days after fertilization
- can be detected in maternal serum about 8 days after fertilization
- can be detected in urine 14 days after fertilization
how come rotavirus can have reassortment (genetic shift)?
because they have segmented genomes capable of genetic shifts through reassortment
most common subtype of germ cell tumor
teratomas= have hair follicles, skin, teeth, bones, and other tissues if mature (cell lines of > 1 germ layer)
what is primary ciliary dyskinesia (PCD)
autosomal recessive
*disfunction of flagella and cilia
- ->situs inversus (reversed right and Left organs)
- -> bronchiectasis (permanent airway enlargement)
- -> infertility
- ->chronic sinusitis
gestational choriocarcinoma
malignant tumor from trophoblast
- hematogenous spread
- lungs= most common site of metastasis
- abnormal proliferation of mononuclear cytotrophoblasts and multinuclear syncytiotrophoblasts
- no villi
clinical finding of gestational choriocarcinoma
- preceded by pregnancy
- causes abnormal vaginal bleeding, uterine enlargement, and increased beta-hCG
- metastasis to lung
second-trimester quad screen test results for Down syndrome
low maternal serum alpha-fetoprotein and unconjugated estriol
high beta-hCG and inhibin A
which cell type produce anti-Mullerian hormone
sertoli cells
which cell type stimulates Wolffian ducts to develop into internal male reproductive organs?
Leydig cells–secrete testosterone
what is an imperforate hymen
obstructive lesion caused by incomplete degeneration of the central portion of the fibrous tissue band connecting the walls of the vagina
*present with primary amenorrhea with cyclic ab pain due to accumulation of menstrual blood in vagina and uterus
histological findings of fibroadenoma
(most common benign tumor of breast)
cellular or myxoid stroma that encircles and sometimes compresses epithelium-lined glandular and cystic spaces
methylmalonic acidemia: what is it? and lab findings?
organic acidemia due to complete or partial deficiency of methylmalonyl-CoA mutase.
hyperammonemia, ketotic hypoglycemia, and metabolic acidosis, elevated urine methylmalonic acid and propionic acid
what is cerebral amyloid angiopathy?
beta-amyloid deposition in the walls of cerebral arteries –> vessel wall weakening –>rupture
*common cause of spontaneous lobar hemorrhage (recurrent; involves the occipital and parietal lobes)
mechanism of action of tricyclic antidepressants (TCAs)
inhibit reuptake of NE and 5-HT
inhibit fast Na+ channel conduction, slowing down myocardial depolarization –> cardiac arrhythmias and refractory hypotension (common causes of death in overdose)
cerebellar hemispheres are responsible for motor planning and coordination of the _______ extremities
ipsilateral
hyperactivity of the ______ pathway is associated with positive symptoms of schizophrenia, whereas low activity of the ________ pathway is associated with negative symtoms
mesolimbic; mesocortical
thymoma is associated with __________
myasthenia gravis
*benign neoplasm of thymus
anesthetics with higher blood solubility have ______ blood/gas partition coefficients
larger
larger partition coefficients/ higher solubility–> needs larger amounts to be absorbed before the blood becomes saturated so slower onset of action
function of the glossopharyngeal never
gag reflex; general sensation of the upper pharynx, posterior tongue, tonsils, and middle ear cavity; loss of taste sensation on the posterior third of the tongue
how can buprenorphine precipitate withdrawal in opioid-tolerant patients?
- it’s a partial opioid agonist that has low intrinsic activity (efficacy) for opioid mu-receptors
- binds w/ high affinity (potency)and prevent binding of other opioid medications (act as opioid receptor antagonist)
phrenic nerve irritation cause
dyspnea, hiccups (diaphragmatic irritation), and referred pain tot he shoulder (area innervated by supraclavicular nerve originating from C3 and C4
“red ragged” muscle fibers are seen in _____________ myopathies
mitochondrial
have this appearance because abnormal mitochondria accumulate under the sarcolemma
Klinefelter syndrome
47, XXY or more X
tall stature; small, firm testes; azoospermia; gynecomastia; mild intellectual disability
Marfan syndrome-caused by
inherited defect of the extracellular matrix protein fibrillin
marfan syndrome- clinical findings
tall with long extremities; pectus carinatum or pectus excavatum; hypermobile joints; long, tapering fingers and toes (arachnodactyly); cystic medial necrosis of aorta; aortic incompetence and dissecting aortic aneurysms; floppy mitral valve. dislocation of lenses, typically upward and temporally
pregnant mom with rubella infection–>
women with polyarthritis and poly arthralgia
infant with sensorineural deafness, cataracts, and cardiac malformations (PDA)
mechanism of action of flutamide
nonsteroid agent that acts as competitive testosterone receptor inhibitor
PCOS is associated with
- oligomenorrhea, hirsutism, and polycystic ovaries
* increased risk for endometrial hyperplasia/carcinoma and type 2 diabetes
Risk factors for cervical cncer
*infection w/ high-risk HPV strains (16, 18) (strongest risk)
*history of STD
*early onset of sexual activity
multiple or high-risk sexual partners
*immunosuppression
*oral contraceptive use
*low SES
*tabacco use
granulosa cell tumors
sex-cord stromal tumors of the ovary that secrete estrogen and can cause endometrial hyperplasia
inhibin
secreted by sertoli cells to inhibit FSH–> stop sertoli cells from making sperm
LH
produce testosterone/ estrogen
somatic vs germline mosaicism
somatic: affects cells forming the body, cause disease manifestations to develop in affected individuals (milder form of turner syndrome)
germline: affect cells that give rise to gametes so affect the offspring
prostatectomy or injury to the prostatic plexus can cause
erectile dysfunction
estrogen stimulates upregulation of ______________________ between individual myometrial smooth muscle cells
gap junctions
gap junctions consist of aggregated connexin proteins
what is primary amenorrhea
absence of menses by age 145 in someone who has normal growth and secondary sexual characteristics
or
absence of menses by age 13 in girls without secondary sex characteristics
cystic fibrosis-clinical findings
recurrent pneumonia, digital clubbing, azoospermia (due to absence of vas deferens), nasal polyps, pancreatic insufficiency
incomplete obliteration of the processus vaginalis leads to ______ and_____
communicating hydrocele (fluid in scrotum); indirect inguinal hernia
gonadal arteries on both sides arises form the
abdominal aorta
*only the left gonadal vein and left suprarenal vein comes from the renal vein
gonadal arteries on both sides arises form the
abdominal aorta
*only the left gonadal vein and left suprarenal vein comes from the renal vein
FSH roles in females
stimulates ovary to recruit 1 primary follicle on the onset of menstruation (day 1)
stimulates granulosa cells inside the follicle to produce estrogen
_______ (hormone) increases the most in concentration after ovulation
progesterone—> to sustain the corpus luteum
cancers of the pelvis, including prostate, spread to lumbosacral spine via ______
vertebral venous plexus (communicates with lots of venous networks like prostatic venous plexus)
placenta accreta
a placenta that is morbidly adherent to the myometrium
scar from prior surgery lead to absent decidual layer so placenta can have direct myometrial attachment by the villous tissue
epithelial ovarian cancer- increased levels of _________
cancer antigen 125 (CA-125)
most common subtype of ovarian cancer (out of epithelial, germ cell, and sex cord stroma)
what is synaptophysin
transmembrane glycoprotein found in the presynaptic vesicles of neurons, neuroectodermal and neuroendocrine cells
neoplasms of glial origin (astrocytomas, ependymomas, and oligodendrogliomas)
glial fibrillary acidic protein (GFAP)
meningiomas
benign tumor cells of the arachnoid villi
neurofibromatosis type 1
autosomal dominant
*cafe-au-lait spots, neurofibromas (lumps all over body), lisch nodules (pigmented, asymptomatic hamartomas of the iris), pseudoarthorsis, scoliosis, other associated tumors (meningiomas, astrocytomas, gliomas, pheochromocytomas)
thiamine (vitamin B1) is a cofactor for:
1) pyruvate dehydrogenase to convert pyruvate into acetyl-CoA
2) alpha-ketoglutarate dehydrogenase, an enzyme of the citric acid cycle
3) branched-chain alpha-ketoacid dehydrogenase to break down BCAA
4) transketolase- enzyme of pentase phosphate pathway that helps convert ribulose 5-P to glycolysis intermediates
thiamine deficiency leads to decreased ______ utilization
glucose
mechanism of action for beta-blockers
inhibiting the neurotransmitter-receptor interaction in adrenergic synapses
naltrexone mechanism of action
blocks the mu-opioid receptor
blocks the rewarding and reinforcing effects of alcohol
restless leg syndrome
uncomfortable urge to move the legs with :
- unpleasant sensations in the legs
- onset with inactivity or at night
- relief with movement
treat with dopamine agonist
what hormones are stimulant medication using to treat ADHD?
they increase availability of norepinephrine and dopamine in prefrontal cortex
standard deviation–> % of data/ confidence interval
SD 1/2/3–> 68/95/99%
neurological syndrome associated with B12 deficiency occurs due to abnormal myelin synthesis–> degeneration of these
1) doral columns
2) lateral corticospinal tracts–> upper motor neuron signs
3) axonal degeneration of peripheral nerves–> numbness or paresthesias
symptoms of Von Hippel-Lindau disease
capillary hemangioblastomas in retina and/or cerebellum, congenital cysts and/or neoplasms in the kidney, liver, and pancreas
increased risk for renal cell carcinoma (bilateral)
rare, autosomal dominant
initial drug of choice for status epilepticus
IV benzodiazepines–> work by enhancing effect of GABA at GABA-A receptor, leading to increased chloride influx and suppression of action potential firing
lateral medullary (Wallenberg) syndrome
caused by posterior inferior cerebellar artery occlusion
vertigo/nystagmus, ipsilateral cerebellar signs, loss of pain/temperature sensation in the ipsilateral face and contralateral body, bulbar weakness, and ipsilateral Horner syndrome
nigrostriatal degeneration in Parkinson –> excessive excitations of the _________________________ by the _________–> excessive inhibition of the_________
globus pallidus internus; subthalamic nucleus; thalamus
Cystic fibrosis- has mutation in FTR gene–> what is the most common kind of CFTR gene mutation
3-base pair deletion of phenylalanine at aa position 508.
mutation–> impaired post-translational processing (improper folding and glycosylation ) of CFTR
rubber-like properties of elastin are due to ________ between elastin monmers, which is facilitated by _____________
cross-linking; lysyl oxidase
medication to help patients with cessation of tobacco by reducing withdrawal cravings and attenuating the rewarding effects of nicotine
varenicline= partial agonist of nicotinic acetylcholine receptors
mechanism of action for combined hormonal contraceptives
supress GnRH in the hypothalamus–> decrease gonadotropins FSH and LH in the anterior pituitary–> prevent the LH spike needed for ovulation
turner syndrome is due to what mutation
meiotic nondisjunction during gametogenesis
*loss of one X chromosone
meconium ileus-what is it and what disorder is it associated to?
distal small bowel (ileum) obstruction due to abnormally dehydrated meconium in a patient with cystic fibrosis (CF)
Ebstein’s anomaly- characteristics and what causes it?
apical displacement of the tricuspid valve leaflets, decreased volume of the right ventricle, and atrialization of the right ventricle
caused by exposure to lithium for treating bipolar disorder
primary oocytes are arrested in ______ of meiosis ___ until ovulation
prophase; I
secondary oocytes are arrested in ______ of meiosis ____ prior to fertilization
metaphase; II
valproate is teratogenic and causes _____
neural tube defects
valproate decreases folic acid level
