test #29 4.19 Flashcards
what surface marker (cell type) is deficient in Bruton’s X-linked agammaglobulimemia?
CD19 (no mature B cells in circulation)
B cell markers
CD19, 20, 21
CD15
neutrophil marker. also present in reed sternberg cells
CD16
NK cells (and others)
two types of abnormal ventilation during sleep
(1) apnea (cessation of breathing for >10 seconds)
2) hypopnea (reduced airflow causing SaO2 to decrease >4%
obstructive sleep apnea
noturnal hypoventilation w/ a transient upper airway obstruction due to poor pharyngeal muscle tone
most common cause of excessive daytime sleepiness
exam: erythrocytosis, obesity, increased soft tissue in oropharynx
arterial blood gas in day: normal
obesity hypoventilation syndrome (aka Pickwickian syndrome)
obesity impedes expansion of chest and abdominal wall during breathing.
increased respiratory work & decreased respiratory drive.
underventilation during all hours (chronically elevated PaCO2 and reduced PaO2)
arterial blood gas = abnormal
differentiation obesity hypoventilation syndrome from sleep apnea?
sleep apnea: normal arterial blood gas in day time
central sleep apnea
patient’s central DRIVE to initiate breaths is absent.
neurological problem (not mechanical)
tumor w/ fat, smooth muscle, blood vessel
angiomyolipoma (benign tumor)
associated w/ tuberous sclerosis
tuberous sclerosis inheritance
autosomal DOMINANT
tuberous sclerosis symptoms
HAMARTOMAS
- hamartomas in CNS and skin
- angiofibromas (face, adenoma sebaceum)
- mitral regurgitation
- angiomyolipoma (renal)
- tuberous sclerosis
- autosomal dOminant
- mental retardation
- ash-leaf patch (hypopigmented)
- shagreen patch (thick leathery, dimpled, organge
also: subependymal astrocytoma and ungual fibromas
NF2
autosomal DOMINANT. bilateral acoustic neuromas.
also have multiple meningiomas, gliomas, ependymomas of spinal cord.
cerebellar hemangiomas, retinal hemangiomas, liver cysts, bilateral renal cell carcinoma, pheochromocytoma
von-hippel-lindau
sturge-weber syndrome
STURGE:
Somatic Tram track Ca2+ opposite gyrus Unilateral leptomeningeal angioma& port-wine stain Retardation GNAQ (activating mutation) & Glaucoma (episcleral hemangioma) Epilepsy
port-wine stain – nonblanching in V1/V2 distribution
developmental anomaly of neural crest derivatives (mesoderm/ectoderm)
hereditary hemorrhagic telangiectasia
Osler-Rendu-Weber syndrome
multiple tenangiectasia of skin & mucosa.
presentation is recurrent epistaxis or GI bleed (melena)
how does B agonists (increased camp) increase contractility?
cAMP increases conductance of Ca2+ channels in SR.
when patient takes exogenous glucocorticoids, worry about..
how is this prevented?
acute adrenal insufficiency (when used for 3+ wks)
prevent by tapering off treatment
where does suppression occur when extended exogenous glucocortoids are taken?
the WHOLE axis: hypothalamic, pituitary, and adrenal!
low CRH, low ACTH, low cortisol!
mutation in NF1
mutation in NF1, tumor suppressor that regulates Ras
autosomal dominant
how does alcohol lead to pancreatitis?
obstruction via ductal concreations & direct parenchymal injury
three types of damage in pancreatitis
(1) pancreatic autodigestion - proteases
(2) vascular damage & hemorrhage - elastase
(3) fat necrosis - lipase / phospholipase
amylase makes..
hydrolyze starch into maltose (a glucose-glucose dissacharide), trisaccharide maltotriose, limit dextins
17 alpha hydroxylase needed for (2)
(1) pregnenolone -> 17 hydroxypregnenolone
(2) progesterone -> 17 hydroxyprogesterone
17 alpha hydroxlase deficiency on secondary sex characterestics
prevents in both males & females.
no menarche in females
5-alpha reductase deficiency on secondary sex characteristics?
abnormal external genitalia development, but will have normal secondary sex (increased muscle mass and phallus enlargement) bc of testosterone
prostate and hair = DHT
urine from umbilicus
persistant allantois remnant
allantois becomes..
URACHUS
urachus
duct between bladder (urogenital sinus) and yolk sac
failure of urachus to obliterate results in..
- patent urachus: umbilicus to bladder: pee from belly button
vesicourachal diverticulum
failure to close part of urachus adjacent to bladder.
outpouching of apex of bladder. commonly asymptomatic.
urachal sinus
failure to close distal part of urachus (adjacent to umbilicus)
periumbicilical tenderness & purulent discharge from umilicus due to persistent and recurrent infection.
vitelline duct
omphalo-mesenteric duct connect yolksac to midgut lumen.
connect small intestine w/ skin at umbilicus
failure of vitelline duct to obliterate
(1) vitelline fistula
(2) meckel diverticulum
vitelline fistula
failure of vitillene duct to obliterate
meconium from umbillicus
meckel’s diverticlum
partial closure of vitilline duct. patent portion attached to ileum (true diverticulum)
ectopic gastric mucosa / pancreatic tissue –> melena, periumbilical pain, ulcers
rule of 2!
2 inches, 2 feet from ileocecal valve, 2% of population, 2 epithelial
omphalocele
incomplete closure of anterior abdominal wall.
– failure of abdominal contents to return to body cavity
presents as ventral opening at the umbilicus, protruding viscera covered by peritoneum
SEALED in peritoneum
gastroschisis
inadequate enlargement of peritoneal cavity during fetal life.
viscera PROTRUDE through defect in anterior abdominal wall adjacent to umbilicus
NOT covered by peritoneum.
closure of abdominal wall (rostral, lateral, caudal)
rostral fold: sternal defects
lateral: omphalocele, gastroschisis
caudal fold: bladder extrophy
duodenal atresia results from..
failure to recanalize
jejunal, ileal, colonic atresia results from…
vascular accident – apple peel atresia
midgut development
6th wk: midgut herniates through belly button
10th: return to abdominal cavity, rotates around SMA, 90 degree counter clockwise
granules in whipple’s disease
diastase-resistant granules in macrophages (lysosomes w/ partially digested bacteria)
what medication can decrease formation of adenomatous polyp formation?
aspirin! cox-2 overexpression in colon mucosa help lead to adenocarcinoma in adenoma-to-carcinoma sequence
adenoma to carcinoma sequence
AK53 & DCC 1. APC (b-catenin) --> AT RISK (cox-2 overexpression & methylation increase too) 2. K-ras -->ADENOMA 3. p53 & DCC --> CARCINOMA
how does APC mutation lead to at risk colon?
APC keeps beta-catenin low –> maintains intercellular adhesion
FAP –> carcinoma always involves..
RECTUM (left, despite being an “exophytic mass’
HNPCC –> carcinoma always involves
PROXIMAL COLON (right, despite not being exophytic)
febuxostat
like allopurinol, inhibits xanthine oxidase
probenicid
blocks reabsorption of uric acid.
so does HIGH dose of salicylates
caspase
cysteine protease
what two enzymes can act on fructose intracellularly
fructokinase (fructose 1-phosphate) and hexokinase (fructose 6-phosphate)
where is fructose absorbed
proximal intestine, facilitative hexose transporter GLUT 5
how is fructose metabolised in essential fructosuria?
absent fructokinase, cannot make fructose-1-phosphate. mostly loose in urine.
BUT small amount converted by hexokinase in liver into fructose-6-phosphate –> phosphoglucomutase turns it into –> glucose 6 phosphate.
can be used for glycogenesis, glycolysis, HMP, etc.
aldolase B converts..
fructose 6-phosphate –> DHAP (dihydroxyacetone P) and glyceraldehyde
glyceraldehyde –> glyceraldehyde 3-phoshpate via triose kinase
galactose metabolism
galactose –> galactose-1-phosphate
(via galactokinase)
galactose 1-phosphate –> glucose 1-phosohate
(via galacose-1-uridyltransferase, which also converts UDP-glucose –> UDP-galactose
UDP glucose is regenerated from UDP galactose with UDP-galactose-4-epimerase
aldose reductase
[low affinity for glucose, only relevant when glucose is high]
converts glucose –> sorbitol.
also galactose –> galactitol
will accumulate if there is no sorbitol dehydrogenase to convert sorbitol —> fructose
which tissues (4) lack sorbitol dehydrogenase? what is the manifestations of this?
lens, schwann cells, retina, kidney.
glucose –> sorbitol via aldose reductase. sorbitol accumulates (can’t convert to fructose).
has osmotic pull. results in..
cataracts, peripheral neuropathy, retinopathy, nephropathy (as seen in diabetes)
acute interstitial pancreatitis vs. acute necrotic pancreatitis
acute interstitial: GROSS EDEMA: microscopic: calcifications. l
ipase digests adipose cells, form fatty acids that bind Ca2+ & ppt calcium salts.
if inflammation continues, trypsin activated, autodigestion of pancreas –
acute necrotic pancreatitis: GROSS CHALKY. destroy vessels –> white chalky fat necrosis. spread onto mesentery, omentum, other parts of abdominal cavity.
mesenteric ischemia on gross
bowel is dusky red and congested. see subserosal ecchymoses, edema, defined necrosis
(probably related to arcades, mult sources of blood to bowel)
calcification on bowel mesentary, omentum, etc
pancreatitis. lipase release free fatty acids, which bind Ca2+ and ppt calcium salts
gastroesophageal mural injury: mallory-weiss vs. boerhaave syndrome?
both caused by forceful vomiting
mallory-weiss: MUCOSAL tear. submucosal arterial or venous plexus bleeding
boerhaave: esophageal TRANSMURAL tear. esophageal air/fluid leakage into mediastinum & pleura
ethanol metabolism
in cytosol:
ethanol –> acetaldehyde
(alcohol dehydrogenase, makes NADH)
in mitochondria:
acetaldehyde –> acetate
(acetaldehyde dehydroganse, makes NADH)
overall increase in NADH/NAD+
why does alcohol cause lactic acidosis?
high NADH/NAD+
need NAD+ for glycolysis, will regenerate AND+ via lactic acid production
pyruvate -> lactate
consume NADH –> NAD+
why does alcohol cause steatosis in liver (2)?
high NADH/NAD+
- glyceradehyde-3-phosphate –> glycerol-3-phosphate. combine w/ fatty acids –> triglycerides
- high acetyl-CoA (due to inhibition of TCA) promotes lipogenesis
TCA inhibited bc oxaloacetate is converted to malate (to regenerate NAD+)
what 4 metabolic pathways are affected by alcohol?
high NADH/NAD+
- pyruvate -> lactate
(consumes NADH–> NAD+) - oxaloacetate -> malate
(consumes NADH –> NAD+) - glyceraldehyde-3-phosphate –> glycerol-3-phosphate
(combines w/ fatty acids to make triglyceride) - blocked TCA, build up acetyl-CoA, permits ketogenesis & lipogenesis
supine hypotension syndrome
aortocaval compression syndrome
hypotension, pallor, sweating, nausea, dizziness
when preggers lady > 20wks lay on back
inheritance of hemochromatosis
autosomal recessive
fairly common among northern europeans
intestinal absorption of iron
usu C282Y mutation on chr 6 in HFE gene
symptoms of hemochromatosis (5)
- micronodular cirrhosis
- diabetes mellitus
- skin pigmentation
- testicular atrophy
- CHF
increased risk of HCC
all related to DEPOSITS of Fe2+
most common source of e. coli bacteremia
URINARY TRACT!
urosepsis risk: BPH, fecal incontinence, neurogenic bladder secondary to diabetes, frequent indwelling catheterization.
why does mucor, rhizopus, absidia <3 diabetic ketoacidosis
have ketone reductase.
proliferate in vasculature, causes downstream tissue necrosis –> black eschar
differentiate paranasal infxn w. aspergillus and mucor?
histology.
aspergillus: acute angle septate
mucor: broad angle, nonseptate
diagnosis of allergic bronchopulmonary aspergillosis
SEROLOGICAL TESTING.
increased IgE and Ab to aspergillus fumigatus = diagnostic
