test #44 5.4 Flashcards
kidney is entirely derived from..
metanephros
metanephric diverticulum (ureteric bud – collecting duct system)
metanephric mesenchyme (glomeruli & tubules)
when does the metanephros develop
5-6th week of gestation
most common cause of unilateral fetal (antenatal) hydronephrosis
ureteric bud = initially solid cord, then canalizes (done by 10th wk)
metanephros can produce urine before ureteric bud canalizes –> hydronephrosis
last segment to canalize: ureteropelvic junction (between kidney and ureter)
cause of antenatal hydronephrosis obstruction
most common:
-ureteropelvic junction (last to recanalize)
other:
- vesicoureteral junction
- posterior urethral valve (membrane in posterior urethra)
when is a fetus able to make urine
8-10th wk
pilocytic astrocytoma on imaging
usu in cerebellum, but can’t be in cerebral hemisphere
cystic component w/ a tumor nodule.
nodule: active part of tumor
most common malignant brain tumor in children
medulloblastoma
exclusively cerebellum
histology of medulloblastoma
small, blue cells. hyperchromatic nuclei, scant cytoplasm
can see homer-right rosettes
histology of ependymoma
perivascular rosettes w/ rod-shaped blepharoplasts (basal ciliary bodies) near nucleus
odds ratio vs relative risk
odds ratio: ad/bc
relative risk: [a/(a+b) / c/(c+d) ]
given chart:
a b
c d
expressing support in interview
express concern independent of understanding.
express concern & interest for patient by acknowledging what the patient says. does NOT claim to know how the patient feels
facilitation in interview
interviewer encourages patient to talk more about experience. asking “and then what happened”
empathy in interview
expression of understanding of experience.
try to “walk in the shoes” to vicariously experience feelings, thoughts, actions.
differs from support, bc tries to project into the experience.
“i can imagine how that experience affected your perspective on life”
reflection in interview
when physicial repeats what patient tells him, i.e. by summarizing
“so, you’re telling me you were molested as a kid”
confrontation in interview
interviewer draws attention to discrepancy in response
“although you say you were disturbed, you sound unaffected as you describe it”
mitral valve problems in rheumatic fever
early: mitral valve regurgitation
late: mitral valve stenosis
death with rheumatic fever
early: myocarditis
late: valvular heart disease –> valvular issues!
diffuse fibrous thickening & distortion of mitral valve leaflets.
commissural fusion at leaflet edges
stenotic orifice w/ diastolic murmur
all suggest
rheumatic fever mitral valvular disease
mitral stenosis –> atrial dilation –> atrial mural thrombus –> stroke
most common cardiac manifestation of rheumatoid arthritis
fibrinous pericarditis
almost all causes of mitral valve STENOSIS are caused by…
chronic rheumatic heart disease
infective endocarditis of mitral valve tends to be..
destructive and regurgitant
mitral valvular calcinosis
usually does not impair valve function
usu in women > 60w/o w/ myxomatous floppy mitral valve or elevated left ventricular pressure
ASD on ausculation
wide fixed S2 splitting.
does not change w/ respiration
split S1?
suggests delayed closure of tricuspid valve, due to right bundle branch block
mid-systolic crescendo-decrescendo
aortic stenosis
early diastolic decrescendo murmur
aortic regurgitation
late systolic crescendo murmur w/ mid-systolic click
mitral valve prolapse
click: sudden tensing of chordae tendinae
most frequent valvular lesion
holosystolic high pitched blowing murmur
mitral regurgitation
holosystolic harsh murmur, loudest in tricuspid area, accentuated w/
VSD
presystolic accentuation
intensity of diastolic murmur before louder just before S1
or when diastolic murmur appears just prior to S1
can result from mitral/tricuspid valve stenosis OR physiological increased flow through valves
systolic ejection murmur accentuated by standing
decrease preload
hypertrophic obstructive cardiomyopathy
early diastolic decrescendo murmur decreased by amyl nitrate
vasodilate –> decrease afterload
aortic regurgitation
late diastolic murmur eliminated by atrial fibrillation
mitral and/or tricuspid stenosis
related to atrial contraction
drug induced lupus
ANA, anti-histone antibody = specific
Q CHIMPPS
quinidine chlorpromazine hydralazine isoniazid methyl-dopa procainimide phenytoin sulfa drugs
also etanercept & minocycline
high risk: hydralazine & procainamide
immediate side effects of adenosine
chest burning, flushing transient hypotension
but has very short half life
vasodilator in chemical cardiac stress tests & stops acute supraventricular tachycardias
where are ureas nitrogen dervived from
- NH3
2. aspartate (sweet pee)
biochemical pathways involving aspartate (3)
-urea cycle (contributes one N)
-pyrimidine synthesis
combines w/ carbamoyl phosphate to make orotic acid (temporary base)
orotic acid + PRPP makes
UMP
this path is blocked in orotic acidura
leflunomide
blocks combination of carbamoyl phosphate + aspartate –> orotic acid
urea cycle
ordinarily, careless crappers are also frivulous about uriantion
ornithine + carbamoyl phosphate –> citrulline + aspartate –> arginninosuscinate –> fumarate (released) + arginine –> urea + ornithine
rate limiting step in urea cycle
carbamoyl phosphate synthase I
remember: I pee
what forms asparagine. relevance?
non essential amino acid.
produced from oxaloacetate in transamination reaction.
oxaloacetate -> aspartate
using glutamate amino group
aspartate -> asparagine
using glutamine amino group
via asparagine synthase
only comes up as site of N-linked modification in golgi
alanine formed by
transfer of an amino group onto pyruvate
parasympathetic agents on blood vessels
do not have cholinergic innervation, but do have muscarinic receptors on ENDOTHELIAL surface
- promote release of NO (endothelium-derivived relaxing factor),
- activates guanylate cyclase,
- increase cGMP
- activates Ca2+ pump &
- causes Ca2+ efflux.
decrease in Ca2+ in vascular smooth wall –> RELAXATION
muscarinics on GI system
increase tone of smooth muscle in viscera; increase motility & secretion, opens sphincters
tibial n. sensation & motor
can’t TIP toe w/ damage
inversion & plantar flex & toe flex
plantar region of foot
common peroneal n. sensation & innervation
foot dropPED w/ damage
eversion & dorsiflex
dorsum of foot
cutaneous medial leg?
cutaneous branch of saphenous n (branch of femoral)
accentuated second heart sound over upper left sternal border suggests..
pulmonary HTN
common cardiac features that can be seen in CREST
pulmonary HTN –> leading to cor pulmonale (right heart failure)
pathogenesis of CREST and systemic sclerosis
increased proliferation & accumulation of monoclonal T cells in affected tissue
secrete cytokine, esp TGF-b, increase production of collagen & ECM by fibroblasts
any tissue affected
SMALL ARTERIOLES & capillaries FIRST
presentation of lichen planus
6 P’s
pruitic, purple, polygonal, planar, papules & plaques.
mucosal involvement
Wickham striae: reticular white lines
sawtooth infiltrate of lymphocytes at dermal-epidermal junction
associated w/ hep C
most common cause of death in scleroderma
pulmonary!
interstitial fibrosis or
pulmonary HTN –> COR PULMONALE
neisseria meningitidis vaccine
capsular polysaccharide vaccine
meningitis in young college student w/ purpuric rash
neiseria meningitidis
virulence factors in neisseria meningitidis
- polysacharide capsule
- IgA protease
- LPS endotoxin
- pili (attach on respiratory mucosa)
5.
heat-killed bacteria vaccine
bordetella pertusis, vibrio cholera, yersenia pestis vaccine
borrelia burgdorferi vaccine
recombinant bacterial outer surface protein
corynebacterium diptherium & clostridium tetani vaccine
inactivated toxin (toxoid)
BCG vaccine
TB: live attenuated organisms of a different mycobacterium species
salmonella typhi & francisella tularensis vaccine
live attenuated
protein A
staph aureus
IgA protease
SHiN
strep pneumo
haemphilus influenza
neisseria meningitidis
where is proinsulin cleaved to insulin + c-peptide?
endoplasmic reticulum of beta-pancreatic cells
what is a good marker of total rate of B-cell endogenous insulin secretion
C-peptide
unlike insulin: C-peptide is not significantly extracted on first pass through the liver!
what drug stimulates insulin release from pancreas
sulfonyureas
also GLP-analogues
GLUT-2 transporter
liver and pancreas
how do GLP-1 analogs increase insulin secretion
increase cAMP, which increases insulin secretion
99mTc-pertechnetate detects..
gastric mucosa
diagnosis of meckel diverticulum
pertechnetate radionucleotide study
accumulates in gastric mucosa &zenker diverticulum often forms gastric / pancreatic tissue
how does meckel diverticulum form
failure of complete obliteration of omphalomesenteric duct / vitelline duct
most common manifestation of meckel diverticulum?
lower GI bleed & RLQ pain (due to acid secretion by ectopic gastric mucosa)
could also cause intusseception – colicky abdominal pain, currant jelly stool
inflammed meckel diverticulum difficult to differentiate from..
acute appendicitis
failure of proper descent of hindgut
different degrees of anal agenesis or imperforate anus
abnormal midgut rotation around SMA can lead too..
fibrous adhesive bands that can lead to intestinal obstruction
genetics of tuner’s
genetically heterogeneous
in cases of monosomy 45 XO: loss of parental X chromosome during mitosis (after fertilization
- 50% complete monosomy (45, XO)
- 30% mosaicism (46 XX / 45 XO)
- remainder have structural abnormalities of X (such that X fragments or isochromosomes) or partial monosomy deletions of X.
weight loss despite normal to increased food intake, polyuria, polydypsia, and fatigue in young adult
type 1 DM
diagnosis of type 1 DM
fasting blood sugar > 126 mg/dL on 2 occasions
only need 1 if symptomatic
when is oral glucose tolerance test used?
usually reserve for pregnant women for gestational diabetes. rarely used. fasting glucose is key.
helicotrema
far part of cochlea w/o basilar membrane, allows for communication of scala vestibuli (top) and scala tympani (bottom)
high frequency sounds on which part of basilar membrane? low frequency?
high frequency: stiff part (base) closer to oval/round window
low frequency: floppy part (apex) near helicotrema
what’s in the inner ear
fluid filled site encased in bone that houses cochlea, semicircular canals & vestibule
fluid in scala vestibuli, scala media, scala tympani
VMT
vestibuli & tympani have perilymph (high Na+ like extracellular fluid)
media (high K+ like intracellular)
what separates scala media from scala tympani
basilar membrane
what is housed in scala media
tectorial membrane & organ of corti
sources of alkaline phosphate. how can it be differentiated (3)?
bone
also: placenta, liver, intestine
can differentiate between liver & bone via..
- electrophoresis &
- specific monoclonal antibodies
- denaturation (bone denatures easy: bone=boil)
tartare resistant acid phosphatase
specific to osteoclasts, but not commonly measured bc not stable protein
calcitonin
inhibit osteoclasts
doesn’t affect osteoblasts much.
urinary deoxypyridinoline and hydroxyproline
measures of osteoclast activity
breakdown of collagen material
note: hydroxyproline not good measure, common in meat products.
most reliable measure of osteoclast activity
urinary deoxypyridinoline
side effects of thiazides
HYPER GLUC increase in.. 1. glucose 2. lipids & cholesterol 3. uric acid: gouty arthritis 4. calcium: useful rx for calcium nephrolithiasis
HYPO:
decrease in
1. potassium
2. BP : decreased blood volume and peripheral vascular resistance
which diuretic is helpful rx for renal nephrolithiasis
thiazides, reabsorb calcium, less in tubules
which drugs increase HDL
niacin and fibrates (via ppar-a)
high HbA2 suggests
thalasemia trait
a2d2 globin
(due to decrease production of a2b2 = HbA1)
Hb types in sickle cell
HbS high
HbA1 low
no affect on HbA2
most common pediatric malignancy
acute lymphoblastic leukemia
distinguishing between pre-B and pre-T cell ALL clinically?
T-ALL present w/ mediastinal mass
can compress..
- great vessels: SVC syndrome
- esophagus: dysphagia
- trachea: stridor, dyspnea
bcell = 80% of cases tcell = 15%
B cell: fever, malaise, bleeding, bone pain, hepatosplenomegaly
black pigment stones
calcium billirubinate
increased unconjugated bilirubin
associated w/ chronic extravascular hemolysis
small, spiculated, crumbly.
radioopaque– appear on X-ray
glucagon’s major effect
liver: increased production of glucose
pancreas: insulin secretion
unlike epinephrine, insignificant affects on skeletal muscle & adipocytes
epinephrine glucose related effects?
- liver: increased glycogenolysis / gluconeogenesis
- skeletal muscle: decrease glucose uptake & increase alanine release (for liver gluconeogenesis)
- adipose tissue: increased breakdown of triglycerides, increasing free fatty acids & glycerol in circulation
kidney’s role in hypoglycemia
first 24 hrs of fasting: liver makes glucose
sustained hypoglycemia: gluconeogenesis in kidney can kick in
major risk of clozapine
agranulocytosis, look at complete blood count
also seizures
clozapine receptor target
D4
unlikely to cause dopaminergic side effects of pseudoparkinsonism, tardive dyskinesia, hyperprolactinemia
(unlike other antipsychotics: D2)
ziprasidone side effect
long QT
leading cause of end stage renal disease in US
diabetic nephropathy
earliest detection of diabetic nephropathy?
microalbuminemia
30-300mg/day in 24hr collection
30-300microgram/mg of creatinine in spot collection
patient w/ dry cough & swollen face & dilated vessels?
superior vena cava syndrome, consider mediastinal mass
SVC syndrome
- facial edema / plethora
- venous distension distal to obstruction
due to mass compressing SVC like lung tumor
impaired venuos return from upper body
where does SVC form
union of right & left brachiocephalic veins behind 1st costal cartilage
most common causes of SVC syndrome
(1) lung mass
2) non-hodgkin’s lymphoma (of perihilar, paratracheal lymph nodes
what hormones does small cell lung cancer secrete
ACTH and ADH
what hormone does squamous cell carcinoma in lung secrete
PTHrP
superior sulcus tumor
i.e. pancost tumor
at lung apex: cause shoulder pain due to compression of bachial plexus & superior cervical ganglion = horner’s
can sometimes cause SVC, but less common than mediastinal mass
inactivation of hep A
water chlorination, bleach (1:100), formalin, UV irradiation, boiling to 85 C for 1 min
will not die w/ frying, 20%diethy ether (bc naked), acid (recall - survives in stomach)
autoclaving
120 degrees for 20 min
boiling in celcius
100
cholesterol med w/ unbearable pruritus & flushing
niacin
mechanism of niacin
decrease synthesis of hepatic TG and VLDL (due to its suppression of free fatty acid release from peripheral tissue)
also increases HDL
how do bile acid resins reduce cholesterol
cholesterol is used in synthesis of bile acids
cholesterol 7a-hydroxylase
side effects of bile acid resins
GI upset
increased TG!
ezetimibe mechanism
reduces reabsorption of cholesterol and bile acids too
what is effective against chlamydia
doxycycline
macrolides
risperidone side effect
hyperprolactinemnia (due to dopamine antagonist effect):
prolactin inhibits release of GnRH from hypothalamus
can lead to amenorrhea, galactorrhea, breast soreness
anytime see amenorrhea
must rule out pregnancy (b-hCG)
“lake-like” cavitary brain lesion
lacunar stroke! HTN arteriolar sclerosis
brain injury that does not show up in acute CT, but later does as cystic space in basal ganglia / deep white matter
think lacunar stroke, occlusion of distal penetrating arteriole
most commonly: due to hypertensive changes in arterioles (lipohyalinosis and microatheromas)
cause of lacunar infarcts
often chronic HTN –> lipohyalinosis, microatheroma –> ARTERIOLAR SCLEROSIS
diabetes & smoking also risk factors
will not present in acute CT, bc small, later show up as lake-like lesion
pure motor hemiparesis
infarct to posterior limb of internal capsule
pure sensory stroke
infarct to VPL or VPM of thalamus
ataxia-hemiplegia syndrome
infarct to base of pons
dysarthria-clumsy hand syndrome
infarct to base of pons or genu of internal capsule
types of infarcts caused by cardiac thrombosis & carotid atherosclerosis
usu strokes often involve large territories, due to involvement of large / medium sized vessels
CAN cause lacunar strokes if no other pathological cause can be identified, but these are most often by arteriolar sclerosis due to HTN
hypoxic encephalopathy defined as
abrupt cessation to CBF, as from cardiac arrest or shock.
more global
pyramidal cells of hippocampus & purkinjee cells & watershed most often affected
hypertensive encephalopathy
leads to cerebral edema due to breakthrough hyperperfusion that is not compensated for by cerebral autoregulation.
headache, nausea and vomiting, other non-localizing neuro symptoms
sequelae of cerebral amyloid angiopathy
results in hemorrhage within cortex & subcortical white matter. not usu ischemic stroke
Charcot-Bouchard aneursyms
microaneursyms < 1mm in diameter. occur in small penetrating arterioles that perfuse basal ganglia, pons, subcortical white matter
due to long standing HTN and prone to rupture
–> hemmorhagic stroke w/ intraparenchyma hyperdensity
what goes into calculating reid index
thickness of gland / thickness of wall between epithelium & cartilage
NOT including cartilage
severity of bronchitis depends on.
extent to which the luminal diameter of bronchi / bronchioles is decreased = reid index
major contributor to increase : thickness of mucous gland layer
normal reid index
40%
in chronic bronchitis > 50%
what rxn does sphingomyelinase normally do
absent in nieman pick
sphingomyelin -> ceramide & phosphorylcholine
enzyme deficiency in metachromatic leukodystrophy & accumulated substance
arylsulfatase A
accumulate: sulfatides
enzyme deficiency in tay sachs & accumulated substance
hexosaminidase A
accumulate GM2 ganglioside
Fabry disease enzyme deficiency & accumulated substances
X-linked recessive
alpha-galactosidase A
accumulate ceramide trihexoside
Farber disease
ceramidase deficiency
autosomal recessive
ceramide accumulation in neurons & within skin granulomas
IV anesthetics (5)
barbituates, benzodiazepines, arylcyclohexylamines (ketamine), opiods, propofol
pharmacokinetics of thiopental (bartibituate)
high potency, high lipid solubility (brain fast), but rapidly redistributed to tissue –> skeletal muscle & fat
induction
decreases CBF
antidote: charcoal / bicarb
IV
benzodiazepine for anesthetic
IV
midazolam, for endoscopy
can combine w/ gas & narcotics.
associated w/ anterograde amnesia and respiratory depression
antidote: flumazenil
IV
arylcyclohexylamine (ketamine) for anesthetic
PCP analogue, dissociated anesthetic. NMDA receptor antagonist.
cardiovascular stimulant, causes disorientation, hallucination, and bad dreams,
increases CBF
IV
opiods for anesthetic
morphine, fentanyl.
used w/ other CNS depressants during anesthesia
IV
propofol for anesthesia
IV
sedation in ICU
rapid induction, short procedure
less postop nausea than thiopental
potentiates GABAa
local anesthetic classes
esters: cocaine, procaine, tetracaine
amides: lidocaine, bupivacaine, mepivacaine
mechanism of action for local anesthetics (esters & amides)
enter cell, bind to voltage gated Na+ channels, prevent AP.
[like class I antiarrhythmics]
enter cell uncharged, bind charged
often given w/ vasconstrictors to increase local concentration
note: if acidic tissue, need increased dose, bc charged species cannot enter cell to work.
order of nerve blockade w/ local anesthetics
size is most important
- small myelinated
- small unmeylinated
- large myelinated
- large unmyelinated
order of loss of sensation w/ local anesthetic
- pain
- temperature
- touch
- pressure
succinylcholine mechanism of action
nAch strong agonist (insensitive to AchE)
depolarizing muscle relaxant
phase 1: sustained depolarization & inactivation.
- POTENTIATED w/ AchE inhibitors
phase 2: desensitized to succinylcholine, but continued block of nAchR (nondepolarizing phase)
- ANTIDOTE w/ AchE inhibitors
side effects: hyperkalemia, hypercalcemia, malignant hyperthermia
important side effects of succinylcholine
increased:
- potassium
- calcium
malignant hyperthermia
nondepolarizing muscle relaxants
nAch antagonists
nondepolarizing muscle relaxants
tubocurarine, atracurium, mivacurium, pancurionium, vecuronium,
reversal: AchE inhibitors (+ atropine, to prevent muscarinic effects)
AchE inhibitor during phase I of succinylcholine? phase II?
phase I: depolarizing / inactivating. potentiate
phase II: nondepolarizing block: antidote
AchE inhibitor w/ nondepolarizing muscle relaxant (tubocurarine, etc)
antidote! give atrophine to block muscarcinic effects
dantrolene
prevent release of Ca2+ from sarcoplasmic reticulum
used as rx: for malignant hyperthermia & neuroleptic malignant syndrome
time frame of succinylcholine vs. nondepolarizing NMJ blockers
succinylcholine more rapid (60 seconds)
train-of-four stimulation response
used during anesthesia to assess degree of muscle relaxation
stimulate presynaptic neuron & increase Ach in cleft. like an AchE inhibitor
train-of-four response to phase I succinylcholine
no response initially
then quickly will gave gradually increased equivalent response in subsequent sets of stimulations
(bc normally quickly metabolized by plasma cholinesterases)
train-of-four response to phase II succinylcholine
mirrors nondepolarizing NMJ blockers
nAchR insensitive to depolarization by succinylcholine, but will still block the receptor.
fading pattern w/ progressive reduction in each of the 4 responses
fading, bc of blockade of presynaptic nAchR preventing preparation of vesicle fusion.
train-of-four response to nondepolarizing NMJ blockers
nAchR antagonists
fading pattern w/ progressive reduction in each of the 4 responses.
occurs bc nAchR antagonists prevent presynaptic neuron from preparing additional vesicles for release
mirror phase II succinylcholine
duration of action of succinylcholine? variation?
determined by
1. diffusion out of NMJ &
2. metabolism by plasma cholinesterase
(insensitive to AChE)
usu < 10min
but! 1/3000 pt homozygous for atypical plasma cholinesterase, which breaks succinylcholine SLOWLY over 1-3 hrs.
neostigmine early: potentiate
neostigmine late: antidote
explain normal train-of-four response
stimulate presynaptic neuron & measure depolarization in muscle
in sequential twitches, presynaptic nAchR play an important role in preparing additional vessicles for release
*impt when using NMJ blockers that are depolarizing agonists / nondepolarizing antagonists
train-of-four response to succinylcholine in phase I
sustained and equal reduction of all 4 twitches
can overcome w/ additional train-of-four bc drug is metabolized by plasma cholinesterase
succinylcholine transition from phase I to phase II
occurs w/ continued infusion
- depolarized & inactivated
- eventually desensitize to succinylcholine; acts as a nondepolarizing nAchR blocker
will also block / inactivate presynaptic nAchR needed to prepare vesicles for fusion in phase II
normally succinylcholine rapidly degraded via plasma cholinesterase: phase I then gone.
how many Ach molecules must bind to nAchR?
2 molecules!
whenever have a drug that is dependent on -esterase, worry about? (i.e. drugs metabolized by AchE)
slow and fast metabolizers!
atracurium special considerations
- safe w/ renal & hepatic impairment
- spontaneous breakdown to: laudonisine, which can cause SEIZURES
- activates histamine -> BP fall, flushing, bronchoconstriction
mivacurium special considerations
- very short acting
2. metabolized by AchE (therefore: consider slow / fast metabolizers)
special considerations with NMJ blockers
paralytics! patient can still sense things! must give anesthetic & analgesics too.
impt feature of nAchR
desensitizes quickly! generally, too much Ach –> depolarization –> cholinergic crisis, which can happen w/ overmedicating for myasthenia gravis.
why does succinylcholine trigger malignant hyperthermia?
initially depolarizes muscle, lots of Ca2+ release and ATP generation
dilated esophagus, microbial cause? congenital?
microbial: esp from central / south america: trypanosomi cruzi
congenital: achalasia
neurotoxin in trypanosoma cruzi?
destroys myenteric plexus in esogagus. similar in colon & ureter
–> megaesophagus, megaureter, megacolon
(also dilated cardiomyopathy)
babesia divergens infxn
endemic in northeast US.
transmitted by ticks
malaria-like illness w/ predilection for asplenic patients
fever & hemolytic anemia
see blood smear w/ maltese cross or ring
rx: atovaquone & azithromycin
brucella melitensis
drinking infected milk / contact w/ infected sheep & goats
fever, malaise, lymphadenopathy, hepatosplenomegaly
“undulating fever”
camplyobacter fetus / intestinalis
opportunistic pathogen
infects immunocompromised
septicemia in newborns, women in 3rd trimester of pregnancy, debilitated elderly
intial steps of ketogenesis
start from: leucine / lysine
or
acetyl-CoA –> HMG CoA
via HMG CoA synthase
HMG CoA –> acetoacetate
via HMG CoA lyase
acetoacetate –> B-hydroxybutyrate
via NADH -> NAD+
where does ketogenesis occur
mitochondria of hepatocytes
metabolism of ketones
in mitochondria of: skeletal muscle, cardiac muscle, renal cortex, brain. (not RBC)
b-hydroxybutyrate -> acetoacetate
acetoacetate –> acetoacetate CoA
via thiophorase
(convert succinyl CoA –> succinate)
acetoacetate –> 2 acetyl CoA
what is the major stimulus for ketogenesis
increase in acetyl-CoA
due to..
depletion of oxaloacetate.
- starving: oxaloacetate used in gluconeogenesis
- alcoholic: NAD+ depletion converts oxaloacetate -> malate (to generate more NAD+)
which 2 cells cannot use ketones
- RBC; no mitochondria
- hepatocytes (liver): no thiophorase / succinyl-CoA-acetoacetate CoA transferase
can’t convert acetoacetate –> acetoacetyl CoA
2 mechanisms for removal of cholesterol
- excretion of free cholesterol in bile
2. conversion to bile salts (cholesterol 7-a-hydroxylase)
bile acid synthesis steps
cholesterol -> cholic & chenodeoxycholic acid
via: cholesterol 7-a-hydroxylase
(rate limiting step)
conjugated w/ taurine / glycine
–> bile salt
what solubilizes cholesterol in bile?
bile salt & phosphatidylcholine
abnormal keratinization of mucus-secreting columnar epithlelium suggests
vitamin A deficiency
epithelial cell metaplasia
can occur w/ cystic fibrosis
fat-soluble vitamin deficiency & damage to glands w/ inspissated mucous
most likely outcome of hepatitis B infection
acute hepatitis w/ complete resolution
possible outcomes w/ hepatitis B infection
most common: 1. acute hepatitis w/ complete resolution >95%
- chronic hepatitis
w/ or w/o cirrhosis & increased risk of hepatocellular carcinoma (4-5% chronic hepatitis; of those 20-50% develop cirrhosis; those 10% get HCC) - fulminant hepatitis w/ massive liver necrosis (<1%)
fate of patients w/ chronic hepatitis B infection
only occurs w/ 4-5% of hep B infxn
20-50% develop cirhhosis
10% HCC
(hep B–> usu acute hepatitis w/ complete resolution)
ras
proto-oncogene
cancer of bladder, lung, colon, pancreas, kidney
n-myc
proto-oncogene
neuroblastoma
small cell lung cancer
erb-b1
proto-oncogene
squamous cell carcinoma of lung
TGF-a
proto-oncogene
astrocytoma, hepatocellular carcinoma
sis
proto-oncogene
astrocytoma, osteosarcoma
abl
proto-oncogene
CML
ALL
BRCA-1, BRCA-2
tumor suppressor
DNA repair gene
breast & ovarian cancer
NF-1
tumor supressor
neuroblastoma
neurofibromatosis 1
sarcoma
APC/B-catenin
tumor supressor
gastric
colonic
pancreatic cancer
FAP
DCC
tumor supressor
colon cancer
P53
tumor supressor
majority of cancer
Li-fraumeni
Rb
tumor supressor
retinoblastoma
osteosarcoma
G1-S
WT-1
tumor supressor
wilms tumor
pediatric kidney, primitive glomeruli
etiology of ARDs
widespread injury to pulmonary microvasculature endothelium and/or alveolar epithelium
–> causes alveolocapillary membrane to be leaky
where do atherosclerotic plaques normally form
in large elastic arteries
(aorta, carotid artery, iliac artery)
& larger medium caliber muscular artery
(coronary, popliteal)
usu not pulmonary artery
hyperosmotic volume contraction cause (2)
- diabetes insipidus
2. profuse sweating
GI hemorrhage alters what fluid volume
isotonic fluid loss from ECV only
bc loose both fluid & osmoles, no pull on fluid from intracellular component
most common cause of death in diabetic?
coronary heart disease!
MI (40%)
(even though have ESRD, still die from coronary heart disease)
stroke also happen, but only 10%
HIGHEST risk factors for coronary heart disease
- noncoronary atherosclerotic disease
- diabetes mellitus
- chronic kidney disease
these basically = coronary heart disease equivalents
also: HTN, hyperlipidemia, cigarette smoking, advanced age, obesity, physical inactivity
leading causes of ESRD
- diabetes
2. HTN
lung: nodular apical densities w/ calcified nodes filled w/ birefringent particles surrounded by fibrous tissue
silicosis
silicosis is defined by
upper lobe nodular densities on x-ray
- eggshell calcifications of hilar nodes
- birefringent silica particles surrounded by fibrous tissue
x-ray of asbestosis
interstitial pattern, more prominent in lower lobes.
calcified pleural plaques
histology: ferruginous bodies, best w/ prussian blue stain
berylliosis x-ray & histology
ill-defined nodular or irregular opacity on x-ray
hilar adenopathy 40%
histology: noncaseating granulomas like sarcoidosis
inhalation of organic dust on x-ray, histology
hypersensitivity pneumonitis
diffuse nodular interstitial infiltrates
histology: noncaseating granuloma (foreign body response)
which 3 lung diseases can have noncaseating granulomas
- sarcoidosis
- hypersensitivity pneumonitis w/ organic dust inhalation
- berylliosis
coal worker pneumoconiosis
x-ray: interstitial opacity
nodal / perilymphatic lung tissue coal dust-laden macrophages
most common cause of SCD
death within 1 hr of cardiac symptom
usu cardiac arrhythmia –> ventricular fibrillation
Caplan syndrome
rheumatoid arthritis & pneumoconioses w/ intrapulmonary nodules
