systemic / genetic / metabolism Flashcards
1
Q
what is the fundamental problem seen in ds of mucopolysaccharidoses? be specific What is the name of Type 1 and Type mucopolysaccharidoses, and what is etiology of ds for each
A
=impaired breakdown of glycosaminoglycans in lysosomes due abn enzyme activity and functioning that allows for the build up of active GAGs in lysosomes–> thick tissue and gargoyle features “glycosaminoglycans” = hexosaminidase, glucoronidase, galactosidase, fucosidase TYPE 1= Hurler Syndrome -AR x α-L-iduronidase = build up heparan+dermatan sulfate TYPE 2= Hunter Syndrome -XR x iduronate-2-sulfatase = build up heparan+dermatan sulfate
2
Q
what is the common clinical presentation in ds of mucopolysaccharidoses? what sx are seen in types 1+2? compare and contrast diagnostic findings?
A
= inherited: child 1-3 years old with “course facial features” and skeletal abnormalities (joint contractures, “dystosis multiplex” on x-ray), poor growth =death within first decade T1= Hurler Syndrome= -progress intellectual and physical delay, airway obstruction, corneal clouding, hepatosplenomegaiy T2= Hunter Syndrome -milder that T2, w/o corneal clouding =macrocephaly w physical and intellectual retardation, =hx of abd hernias, infections, recurrent sinus infections/colds, cardiac/pulm HTN ds, hearing loss **may present with only skeletal abn and poor growth, DIAGNOSE with findings of abn lysosomal storage and inc GAG function
3
Q
kartagener syndrome etiology presentation/sx
A
=primary ciliary dyskinesia 2° defect in dynein arm of microtubules -TRIAD= situs invertus, chronic sinusitis, bronchiectasis =most males will be infertile =100% pts have sinus change = nasal polyps
4
Q
hypoxic necrosis in body tissue is ____ necrosis, except for in the CNS where it is _____ necrosis: the latter type only exists outside of the CNS in the setting of..
A
coagulative liquefactive bacterial/fungal infection (presents as pus)
5
Q
how does infection w C. perfringens vs B. fragilis present what is the basic classifications of these bug??
A
C perfringens: gas gangrene, often to the LE s/p trauma (crush injury, dog bite, etc) ****gas gangrene = myonecrosis -can be found on surgical debridement B. fragilis= post-trauma/injury abscess in the GI tract/pelvis area -natural gut flora C perfringens= G+ rod, anaerobic, infect via endospores B. fragilis= G- rod, anaerobic
6
Q
acetaminophen MOA AE -what population is especially susceptible to the AEs
A
MOA= reversible inhibition of COX *in the CNS* !! (inactivated peripherally) AE= OD–> hepatic necrosis via depletion of glutathione + formation of toxic tissue byproducts in hepatocytes —**glutathione= an antioxidant**: alcoholics= especially susceptible
7
Q
aspirin MOA AE
A
MOA: irreversible inhibition of COX1+COX2 –> dec TXA2+ prostoglandins = inc bleed time, no effect coag tests *COX1= in gastric mucosa* *COX 2=inflammatory cells and vascular endothelium* AE= gastric ulceration, tinnitus, chronic= AKI, interstitial nephritis, GI bleed, Reye toxic dose: resp alk–> mixed met acid+resp alk
8
Q
celecoxib MOA indication AE
A
MOA= reversible selectively inhibit COX2 (only in inflammatory cells and vasc endothelium) –> mediate inflammation and pain indication= RA, OA AE= inc risk thrombosis, sulfa
9
Q
NSAIDS (high yield drugs) MOA AE
A
(ibuprofen, naproxen, indomethacin) MOA= reversibly inhibit COX1+COX2 –> block prostoglandin synthesis AE= interstitial nephritis, gastric ulcer, renal ischemia, aplastic anemia
10
Q
leflunomide MOA AE
A
MOA= reversible inhibition of pyrimidine synthesis –> suppress T cell prolif AE= hepatotoxicity, teratogenic, HTN, diarrhea
11
Q
bisphosphonates (high yield drugs) MOA indication AE
A
(__-dronate : alendronate, ibandronate, risedronate, zoledronate) MOA= inhibit osteoclast activity indication: osteoporosis, hyperCa, paget ds of bone, metastatic bone ds, osteogenesis imperfecta AE= esophagitis if oral, osteonecrosis of jaw, atypical femoral stress frx
12
Q
what AA precursors and vitamin cofactors are needed for the production of thyroxine?
A
phenylalanine –> tyrosine –> thyroxine *need BH4
13
Q
what AA precursors and vitamin cofactors are needed for the production of melanin
A
phenylalanine –> tyrosine –> Dopa –> melanin *need BH4
14
Q
what AA precursors and vitamin cofactors are needed for the production of dopamine
A
phenylalanine –> tyrosine –> Dopa –> dopamine *need BH4, Vit B6
15
Q
what AA precursors and vitamin cofactors are needed for the production of NE
A
phenylalanine –> tyrosine –> Dopa –> dopamine –>NE *need BH4, Vit B6, Vit C
16
Q
what AA precursors and vitamin cofactors are needed for the production of epinephrine
A
phenylalanine –> tyrosine –> Dopa –> dopamine –>NE –> epinephrine *need BH4, Vit B6, Vit C, methionine
17
Q
what AA precursors and vitamin cofactors are needed for the production of niacin what is niacin needed to produce
A
tryptophane –> niacin *need Vit B2+B6 niacin–> NAD/NADH
18
Q
what AA precursors and vitamin cofactors are needed for the production of serotonin what is serotonin needed to produce
A
tryptophan –> serotonin **need BH4+ Vit B6 serotonin –> melatonin
19
Q
what vitamin is needed to produce histamine
A
histidine –> histamine **need Vit B6
20
Q
what AA precursors and vitamin cofactors are needed for the production of porphyrin what is porphyrin needed to produce
A
glycine –> porphyrin *needs B6 porphyrin –> heme
21
Q
what AA precursors and vitamin cofactors are needed for the production of GABA
A
glutamate –> GABA *need B6
22
Q
what AA precursors and vitamin cofactors are needed for the production of glutathione
A
glutamate –> glutathione *no vit needed
23
Q
arginine is the precursor AA needed in the metabolism of what 3 biochemical substances in our body
A
arginine gives rise to.. -creatine (found in Ms) -urea -nitric oxide
24
Q
in what cells do HSV1 and HSV2 virus lie dormant
A
sensory neurons HSV 1- in trigeminal ganglia HSV 2- in sacral ganglia
25
what is the functional difference between proteosomes and lysosomes
Lysosomes digest excess or worn out organelles, food particles, and engulfed viruses or bacteria Proteasomes degrade unneeded or damaged proteins that have been ubiquinated
26
granuloma formation is dependent on \_\_\_\_\_, which is made by \_\_\_, and functions to recruit Møs
IFN-y made by Th1 cells (x in AIDS pts--\> cannot fight TB..)
27
Lymphocyte function-associated antigen 1 (LFA-1) function?
LFA-1 binds ICAM proteins (i.e. CD-54) on vasc cells to -promote emigration of lymphocyte cells -also mediate leukocytes, and work w CD8 cells
28
outline the process of NFkB activation
IL-1 / TNF activate IKK (IkB-K) in Th cell ↓ IkB phosphorylation --\> ubiquination --\> proteolysis ↓ NFKB now free to enter nucleus of Th cell ↓ inflammatory/immune response : cell prolif/survive
29
during normal M twitches, ATP concentration does not fall considerably because \_\_\_\_?
ATP is quickly regenerated from creatine phosphate\*\* \*\*a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine triphosphate, the energy currency of the cell
30
differentiate between -variable expressivity -incomplete penetrance -gonadal mosaicism
variable expressivity: pts with the same genotype have diff phenotypes incomplete penetrance: not all individuals with a mutant genotype will show the mutant phenotype gonadal mosaicism: mutations occurs spontaneously in the egg or sperm: parents and relatives DON'T have the ds
31
EBV is part of what virus family
what is the classic ds associated w EBV
associated with what CAs
herpesviridae
=mono (fever, pharyngitis, cervical lymphadenopathy, splenomegaly)
--nasopharyngeal CA
--Burkitt lymphoma (endemic in Africa: large jaw lesions present)
---Diffuse Large B Cell Lymphoma
--Hodgkin lymphoma
--oral hairy leukoplakia (AIDS pts)
32
francture at the proximal humerus can happen how?
what N will be injured --\> lose what functions? clin presentation?
-frx surgical neck (elderly who falls), ant dislocation (trauma/football)
x axillary N(C5-C6)
- x deltoid M --\> flat deltoid w loss of shoulder ABD \>15 degrees
- loss of sensation over deltoid and lateral arm
33
injury of the musculocutaneous N
what N roots
loss of what functions, clin presentation
upper trunk compression (rare)
(C5-C7)
= xbicep innervation --\> x forearm flexion, x supination
= x sensation over lateral forarm
34
compression of the axilla from crutches, or saturday night palsy leads to lesions of what N
where else can a lesion of this N occur
what are the clinical presentation
= radial N (C5-T1)
## Footnote
- can also happen at midshaft humerus
- repetitive pronation/supination of forearm i.e. screwdriver use
functions extensors of the forearm, wrist, hand and sensation over the extensor surfaces
@axilla: wrist drop (stuck in flexion: lose extension elbow, wrist, fingers) + ↓ grip strength + triceps wkns + x sensation over posterior arm/forearm/dorsal hand
@ radial groove= spare triceps: wk wrist and finger extension, only lose sensation over dorsal hand
35
what N lesion presents with a supracondylar humerus frx
where else can the N lesion occur
clin presentation
median N (C5-T1)
+ wrist laceration, +carpal tunnel syndrome
clin: pope's blessing
- WK\*\* wrist and finger flexion, thumb opposition, 2nd and 3rd lumbricals
- x sensation over thenar eminence and digits 31/2 (dorsal and palmar) w proximal lesion at wrist
\*\*share wrist flexion with ulnar N
36
what N lesion presents with frx of the medial epicondyle of the humerus
where else can this N lesion happen?
clin presentation
ulnar N (C8-T1)
= medial epicondyle of humerus (funny bone), or FOOSH (fall on outstretched hand--\> hamate bone frx)
=claw o the digits 4+5 with extension of fingers
@ medial epicondyle: radial deviation of wrist on flexion + wk wrist flexion +...
@wrist/hand : wk flexion digits 4+5, AB+ADuction of 4+% (lumbricals) : x sensation over medial 1.5 digits + hypothenar eminence
37
loss of thenar opposition, ABduction, and flexion without any loss of sensation suggests what N lesion
recurrent branch of median N
w superficial laceration of palm
38
describe a brancial plexus upper trunk tear
N roots
causes
M deficits + clin presentation
Erb's palsy = waiter's tip
## Footnote
C5-C6
-shoulder dystocia, adult trauma
x deltoid + supraspinatous --\> x ABduction = arm hang by side
x infraspinatous --\> x ER= arm stuck internally rotated
x biceps brachii --\> xflex, sup = arm stuck extended back and pronated (tip)
39
describe a brancial plexus lower trunk tear
N roots
causes
M deficits + clin presentation
Klumpke palsy
## Footnote
C8-T1
-excessive ABduction: fall from tree and try to grab branch \>\> infant delivery
= x ulnar N AND median N --\> complete claw of the hand
x lumbricals of hand (wrist okay bc other Ns) --\> flexe MCPs and extended DIPs and PIPs
40
etiology and clinical presentation of thoracic outlet syndrome
compression of lower trunk of brachial plexus + subclavian vessels
- cervical rib (congenital or 2° to whiplash), pancoast tumor
- present w claw of hand + atrophy of intrinsic hand Ms, + ischemia, pain, and edema of the arm
41
winged scapula presents 2° to lesion of what N
x what M
causes?
x long thoracic C (C5-7) [5-7, wings of heaven]
x serratus anterior M (usually pull scapula against rib cage)
-cannot ABduct arm above horizontal position
∝ axillary N dissection (post mastectomy), stab wounds
42
how do you define normocytic anemia?
how are the normocytic anemias further divided, and what entities fall under each subdivision
**normocytic**= _MCV 80-100_
_low reticulocyte count_= **non-hemolytic**:
-early iron defieincy, chronic ds, aplastic anemia, CKD
high reticulocyte count= **hemolytic**
- **intrinsic**: hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria : G6PD / pyruvate kinase deficiency : sickle cell + HbC ds
- **extrinsic**: autoimmune, micro/macro-angiopathic, infections
43
how do you define microcytic anemia
what etiologies fall under this category
microcytic = MCV\< 80
\*\*TAIL\*\*
= (alpha or beta) thalassemias, anemia of chronic ds, late irone defiency, lead poisening
44
how do you define macrocytic anemia,
what conditions fall under this category
macrocytic anemia = MCV \>100
=**megaloblastic**: folate/B12 deficiency : orotic acidurua or Fanconi syndrome
=not megaloblastic: diamand blackman ds, liver dr, alcoholism
45
iron deficiency anemia
MCV?
causes
labs: iron, TIBC, ferritin, free protophyrin, RDW, reticulocyte index
clin presentation
microcytic anemia= MCV\<80
cause: chronic bleeding, malnutrition/ x absorption, inc demand (pregn)
labs: ↓ iron, ↑ TIBC, ↓ ferritin, ↑ free protophyrin, ↑ RDW, ↓ reticulocyte index
clin: anemia sx + spoon names, glossitis, cheilosis:
may present as Plummer-Vinson syndrome= iron defiency anemia + esophageal webs + dysphagia
46
alpha thalassemia
MCV?
alpha thalassemiaminor: genetics, clin
HbH ds: genetics, clin
Hgb Barts ds: genetics clin
MCV\<80= microcytic
normal genes= (αα/αα): ds w α deletions
α thalassmia minor : (α -/α -) OR (αα/- -)
-mild microcytic, hypochromic anemia: high rates in Asian population bc they have high rates of the second genotype
HbH ds: = (- -/ - α) = HbH is excess β relatively--\> β4 chain formation
=moderate to severe microcytic, hpochromic anemia
Hemeglobin Barts ds= (- -/- -) = no α chain, excess Υ chain = Υ4 forms
-hydrops fetalis= incompatible w life
47
β thalassemia= what is the fundemental etiology, associated what population
β thalassemia minor = genetics? etiology? sx?
β thalassemia major= genetics? etiology? sx?
HbS ds= etiology? clin?
β thalassemia= microcytic anemia from point mutations on chr 11 --\> ↓ β-globin synthesis
-associated w mediterranean populations
--β thalassemia minor= heterozygote--\> underproduced β chain
-inc HbA2 : usually asx
--β thalassemia major= homozygote --\> no β chain produced
-severe microcytic, hypochromic anemia w target cells and ↑ anisopoikilocytosis that requires blood transfusions
----\> chronic transfusions = inc risk of hemachromotosis
- *crew cut skull* on x-ray 2° to marrow expansion, *chipmunk face* 2° sk deformities, hepatosplenomegaly 2° to extramedullary hematopoeisis
- inc risk of parvovirus
HbS= mild to moderal sickle cell ds from dec B-glbin production
48
what are the sx, etiology, and trx of lead poisening
type of anemia
microcytic hypochromic
sx= LEAD
L= **l**ead **l**ines on gingiva (Burton lines) and metaphyses of long bones on x ray
E= **e**ncephelopathy and **e**rythryocyte basophilic stippling
A= **a**bd colic and sideroblastic **a**nemia
D= wrist **D**rop/foot **D**rop
etiology: dec heme synthesis + inc RBC protoporphyrin
1st line trx= dimercarprol and EDTA: succimer for chelation
49
sideroblastic anemia
what is a sideroblast
type of anemia
etiology
labs: iron, TIBC, ferritin, BM smear, peripheral smear
microcytic hypochromic anemia: a sideroblast is an immature RBC that has iron accumulations in the mitochondria 2° to defects in heme synthesis
causes: X linked xALA-synthase, acquired myelodysplastic syndrome,
reversible causes: alc\>\>\> Pb poisening, Vit B6 deficiency, copper deficiency, isoniazid/linezolid
labs: ↑iron, n/↓ TIBC, ↑ ferritin,
BM smear: ringed sideroblasts are iron laden mitochondria =prussian blue stain
peripheral smear: basophilic stippling of RBCs
50
what is the function of granulocyte colony stimulating factor
it stimulates the BM to make more granulotcytes aka leukocytes that release granules aka Nøs, basophils, eosinophils
51
what are the acute phase reactants
markers of inflammation
CRP, complement factors, ferritin, ceruloplasmin, serum amyloid A, haptoglobin
52
what is osteoporosis vs osteomalacia vs osteopetrosis vs paget's ds
lab changes in serum Ca: PO4: alk phos: PTH
osteoporosis: ↓ bone mass
Ca: n PO4: n alk phos: n PTH: n
osteomalacia = the adult form of rickets = low Vit D --\>soft bones
Ca: ↓ PO4:↓ alk phos: ↑ PTH: ↑ (2° to ↓Vit D)
osteopetrosis= dense, brittle bones
Ca: n, then ↓ w late ds PO4: n alk phos: n PTH: n
paget's ds: mosaic bone from inc clast, then blast, then burn out
Ca: n PO4: n alk phos:↑ PTH: n
53
which bone tumors are more associated w males
the *primary*, *_benign_* bone tumors that _start w O:_
- osteochondroma
- osteoma
- osteod osteoma
- osteoblastoma
- osteosarcoma
54
osteochondroma vs chondroma
- epidemiology
- location + origin
- characteristics +prognosis
osteochondroma=
* most common benign tumor: in M\< 25 yo
* tumor of bone, in metaphysis of long bones
* lateral projection of growth plate connected to medullary space, covered by cartilagenous cap : RARE to transform to chondrosarcoma
chondroma
* -
* from the medulla of small bones, found in hands and feet bones
* = benign tumor of cartilage
55
osteoma vs osteiod osteoma
- epidemiology
- location and origin
- characteristics
osteoma
* in middle aged people
* bone tumor: on the surface of facial bones
* ∝ w Gardner Syndrome= AD familial adenomatous polyposis (polyps in colon)
osteoid osteoma
* M adults \<25 yo
* bone tumor: w/in cortex of long bones
* clin= bone pain worse at night that is releived w NSAIDs : radioluscent mass \< 2cm w radioluscent osteoid core
56
osteosarcoma vs chondrosarcoma
- epidemiology
- location and origin
- characteristics
- prognosis
osteosarcoma
* peak incidence= M \<20 yo : less in elderly, usually 2° to risk (Pagets, infacts, radiation, familial retinoblastoma, Li-Fraumanni syndrome)
* = most commonly is 1° tumor of *malignant osteoblasts* = 20% of total 1° bone tumors : metaphysis of long bones, most commonly @ knee
* mc present as painful enlarging mass or pathologic frx : x-ray= Codman's triangle, sunburst radiations :
* 1° is aggressive but responsive to trx, 2° = poor prognosis
chondrosarcoma
* -
* tumor of malignant chondrocytes (Cartilage) : @ medulla of pelvis, proximal femur, humerus
* -
* -
57
giant cell tumor of the bone + Ewing Sarcoma
- epidemiology
- location
- path
- clin
giant cell tumor aka osteoCLASToma
* 20-40 yo
* epiphysis of bone, often @ knee
* neoplastic mononuclear cells that express RANKL + osteoclast-like reactive giant cells
* "soap bubble" on x-ray : benign, but locally aggressive
Ewing Sarcoma
* mc = whites, boys \<15 yo
* diaphysis of long bones (esp femur), + pelvic flat bones
* neuroectodermal: anaplastic small blue cell tumor : t(11,22) EWS:FL11 fusion protein
* onion skinning of periosteum on x-ray : aggressive w early mets BUT v responsive to trx
58
multiple myeloma
- etiology
- clin presentation
- labs and histo
- complications
MM
* overproduction of Ig (mc IgG \>\>\> IgA)
* "CRAB": hyperCa, Renal ds, Anemia, Back pain
* **bone x-ray**= lytic lesions = *"punched out"* : **bloodsmear** shows *Rouleaux* formation : **BM**= plasma cells w *"clock face"* chromatin and IgG cytoplasmic inclusions : **urinalyses**= *Bence Jones* proteinuria (Ig light chains) w (-) dipstick
* complications: inc infection : 1° amyloidosis
59
what effect to NSAIDs + Aspirin (+Celecoxib) have on platelets
--\> what physiologic change?
they decrease plateley aggregration --\> ↑ bleeding time
NO change in # of platelets --\> just inactivate the ones there
60
how does hemoglobin act as a buffer
what version of hemoglobin acts best as a buffer
-when hemoglobin releases O2 into the tissues, it is buffering the simultaneous inc in H+ being made in the tissues due to M work+ eergy production
--- it drops off the O2 and takes away the CO2 (the 'H+')
==\> maintain the pH
DEoxyhemoglobin is a better buffer than oxyhemoglobin
(deox has higher pKa bc it's more acidic)
61
presence of *metamyelocytes, myelocytes, and premyelocytes* on *leukocyte differentiation (blood test)* in an old person w generic sx (fatigue, SOB, etc)..
likely diagnosis?
what if you saw increased *myeloblasts on peripheral smear*?
what are other associations with these pathologies?
1- likely CML = x mature granulocyte production in BM w low activity in malignant nøs
=develop slowly over time: median age= 64 yo
=inc leuokcytes, either high nøs + low alk phos OR low nø w high alk phos (bc used up in inflammation)
↓
↓
can accelerate to AML = see myeloblasts on peripheral smear
=median age 65 : see auer rods too
=may see MPO+ in some subtypes,
= risk for AML ∝ radiation, past chemo, myeloprloif ds, down syndrome
=often present w DIC
62
what are the derivatives of the aortic arches
1 = part of maxillary A (1 is max)
2= stapedial and hyoid A (**S**econd-\> **S**tapedial)
3= **C**ommon **C**arotid +prox Internal **C**arotid As (3 Cs- 3rd letter)
4= L= aortic arch R=prox R subclavian A (4 makes sure you get blood out to your 4 limbs)
5= x
6= prox pulm A + (L-\> ductus arteriosus) (6 = pulm)
63
what are the derivatives of the pharyngeal clefts aka pharyngeal grooves
what is the etiology of a persistant cervical sinus?
how do you differentiate it from a thyrglossal duct cyst?
PC 1/ PG1 = external auditory meatus
PC2-4 / PG2-4 = temporary cervical sinuses
\*will be obliterated by P-arch 2 mesenchyme
persistant cervical sinus= a pharyngeal cleft/groove cysts in the lateral neck, ant to SCM
NO move w swallow (vs TDC, which will move)
64
derivatives of the pharyngeal arches
cartilage
M
N
other/associations
pharyngeal arche's are annoying, but don't be **M**ean(1)- just **Smile** (2)and **Swallow**(3).. **Stop**(4) before you **Speak**(6)
1:
* **M**axillary Process (+zygo**m**atic bone) : **M**andibular process (**M**eckel + mandible) : **M**alleus, Incus (ear), spheno**m**andibular L
* Ms of **M**astication (temporalis, masseter, lat+med pterygoids), **M**ylohyoid, ant belly of digastric, tensor tympani, ant 2/3 tongue, tensor veli palatini
* CN V to chew *_(#1 priority is to eat and talk)_*
* ∝ **Pierre Robin sequence** (micrognathia, glossoptosis, cleft palate, airway obstruction) or **Treacher Collins syndrome** (AD x neural crest--\> craniofascial abn, xhearing, airway compromise)
2.
* Reichery cartilage = **S**tapes, **S**tyloid process, le**ss**er horn of hyoid, **s**tylohyoid L
* **S**mile! (facial expression Ms) = **S**tapedius, **S**tylohyoid, platy**s**ma, post belly of digastric
* CNVII: facial N for Smiling
* -
3.
* greater horn of hyoid
* stylopharyngeus M *(3+4= post 1/3 tongue)*
* CN IX= glossopharyngeal N (swallow)
4+6.
* Arytenoids, Cricoid, Corniculate, Cuneiform, Thyroid
* Ms of 4: pharyngeal constrictors *("stop")*, cricothyroid, levator veli palatini :: *(3+4= post 1/3 tongue)*
* Ms of 6= intrinsic laryngeal and cricothyroid Ms
* 4--\> CN X (superior laryngeal branch: *vagus ~ stop*) :: 6--\> CN X recurrent laryngeal branch
65
which way do Na, K, Cl, and Ca move (in/out of the cell) under physiologic conditions
extracellular gradient: pushes Na, Cl, and Ca into the cell
intracellular gradient: puse K out the cell
66
burn patient with wound infection that is blue-green in appearance
dx?
trx?
pseudomonas infection (inc risk of wound infection in burn pts)
trx: broad spectrum penicillins co-admin w beta lactamase
=piperacillin + tazobactam
67
name and describe the etiology and clin presentation of the diseases linked to abnormalities in the following enzymes:
* β glucocerebrosidase
* acid ceramidase
* acid sphingomyelinase
* α galactosidase A
* hexosaminidase A
* β glucocerebrosidase= **Gaucher Ds**
* ^ = a lysosomal enzyme; deficiency --\> accumulation of lipid laden Møs = "Gaucher Cells"
* always suspect w: anemia/thrombocytopenia AND hepatosplenomegaly AND bone ds
* i.e dec bone density, marrow infiltration, and infarction
* can range from asx to perinatally fatal
* most commonly present in ashkenazi jews, w/o CNS involvment - but can vary
* acid ceramidase = **Classic Farber Ds**
* (a lysosomal enzyme)
* subQ nodules, accumulation of joint contractures, hoarse voice
* range from death in infancy, to not diagnosed until adulthood
* acid sphingomyelinase = **Niemann-Pick TB**
* childhood hepatosplenomegaly, hypersplenism ( thrombocytopenia)
* short stature, delayed skeletal maturation, interstitial lung ds, hyperlipidemia, cherry red maculae
* liver infiltrates = foamy histiocytes, hepatocyte ballooning + fibrosis
* α galactosidase A = **Fabry Ds**
* X-linked, in childhood or adolescence: used in (galactose --\> glucose)
* neuro (limb pain), derm, GI, corneal opacity, proteinuria or DI-like sx
* hexosaminidase A= **Tay Sachs**
* infantile form= death by 4yo, later onset is less aggressive,
* neurodegeneration, delayed onset and gradual decline in motor, cerebral, and spinocerebellar function
68
outline the steps in base excision repair
glycosylase
endonuclease
lyase
polymerase
ligase
69
classical presentation for HUS
what are the common causes
common causes:
* E. Coli O157:H7
* Shigella
Clin Features:
* an anticident diarrheal disease (often bloody)
* (-) Coombs ds
* hemolytic anemia with schistocytes
* dec Hgb and haptoglobin
* inc serum lactate, unconj bilirubin
* thrombocytopenia
* acute kidney injury
*
70
acute onset of fever, cough, congestion, pharyngitis, and conjunctivitis (red, itchy eyes) suggests what path and cause?
pharyngoconjunctival fever
caused by adenovirus (dsDNA virus) associated w crowded areas (day care, military, dorms)
71
nausea+diarrhea w epigastric pain going on for \> 1 week
hx of transient pruritic rash somewhere in the feet or some exposed area of the skin that self-resolved
suggests what? what are common complications of this?
hookworm infection :
* Necator americanus
* ancylostoma duodenale
dermal penetration by the hookworm will result in a transient pruritis in the area OR maculopapular rash
* travel from skin entry --\> lungs --\> alveoli -\> small intestine
* feed on human blood in the small intestine capillaries
* common complication is iron-deficiency anemia (microcytic) due to chronic blood loss
* peripheral eosinophilia can help dx
72
what is the clinical presentation and etiology of:
* wiskott-aldrich syndrome
* chediak-higashi syndrome
* ataxia telangectasia
* SCID
* terminal complement deficiency
* wiskott-aldrich syndrome: a kid named wiskott
* **recurrent infections** that worsen w age
* start at 6 months (lose mom IgGs) unable to make Igs so inc infections w Strep. pnuemo, N. meningitidis, H. influenzae
* oppurtunisitic infections (P. jiroveci)
* **eczema**
* thrombocytopenia --\> easy bleeding
* chediak-higashi syndrome:
* dysfunction of phagocyte-lysosomal fusion --\> giant cytoplasmic granules on peripheral smear
* **oculocutaneous albinism**
* **pyogenic** infections
* progressive neuro dysfunction
* ataxia telangectasia
* x both B and T cells
* ataxia + telangiectasia + sinopulmonary infections
* SCID
* severe viral and bacterial infections in infancy
* chronic diarrhea
* mucocutaneous candidiasis
* terminal complement deficiency
* recurrent **Neisseria** infection
73
list the 5 lysosomal storage diseases
* inheritance + deficiency enzyme
* accumuated substance
* findings
* mnemonic
tay sachs ds
* inheritance + deficiency enzyme
* AR **He**_x_****oaminidase _A_ (t**_a_**y sa_x)_
* accumuated substance
* GM2 **gang**lioside
* findings
* progressive neurodegeneration, **developmental delay**, **cherry-red** spot on macula, lysosomes with **onion skinning**,
* NO hepatomegaly = vs Neimman pick
* ***gang** of **hex**xers, **dumb** **onion** heads spilling **blood** in the streets*
Niemann Pick Ds
* inheritance + deficiency enzyme
* AR x sp**hing**omyelinase
* accumuated substance
* sphingomyelin
* findings
* **progressive neurodegen**eration, **hepatosplenomegaly (growing)**
* **foam** cells = **lipid** laden Møs, **cherry red** spot on macula
* *Niemann is the un**hing**ed cousin from Bulgaria; **fat,** always **foaming at the mouth,** gets **dumber every year** he's at school but hes g**rowing the army** of students to prep for the **blood-spilling** at the hogwarts battle*
**Fab**ry Ds
* inheritance + deficiency enzyme
* XR alpha **galact**osidase A
* accumuated substance
* **cera**mide **trihex**oside
* findings
* early triad: \*episodic **peripheral neuropathy**, \***angiokerato**mas (small, dark spots on skin, \* hypo**hidrosis** (dec sweating)
* late: \*progressive renal failure + \*CV ds
* *a **fable** of a **galaxy**, protected by **3 councils of 6 witches**: one oversaw the **peripheral planets+stars**, one oversaw t**rade and diplomatics**, one made sure the tensions **stayed cool**. but then, it all started to **fail..**.*
**metachromatic** leukodystrophy
* inheritance + deficiency enzyme
* AR x **aryls**ulfatase
* accumuated substance
* **cerebroside** sulfate
* findings
* central and peripheral demyelination with **ataxia and dementia**
* *using **acrylics** to **paint** the **brain**, but don't sniff too much or else you'll get **high** (dementia and ataxia)*
**Krabbe** Disease
* inheritance + deficiency enzyme
* AR x **galact**ocerebrosidase (**gal-lacked-**o**cerebro**sidase**)**
* accumuated substance
* galactocerebroside psychosine
* findings
* **peripheral neuropath**y, destruction of **oligo**dendrocytes, **dev delay**,
* **optic atrophy**,
* **globoid** cells
* *the **gal lacked the brains**, so she became a **krabby**-biotch: she **lost here oligarchy** of "cool kid friends" bc she **stopped feeling**, **fell behind** in classes, and **lost vision** of her future and became a **global mess***
Gaucher Ds
=MOST COMMON
* inheritance + deficiency enzyme
* AR x glucocerebrodase (beta glucosidase)
* accumuated substance
* glucocerebroside
* findings
* hepatosplenomegaliy, **pancytopenia**, osteoporosis, avascular necrosis of the femur, **bone crises**
* gaucher cells (lipid laden macrophages that look like **crumpled up tissue**)
* ***most common** sugar used by brain= **glucose** --\> cause **sx that are commonly seen in other pathologie**s: you're **all out of options** and having a **crisis**- sat ripping the pages out your notebook and **crumpling them all up** bc nothing is original --\> **you're so gauche** (lacking grace, unsophisticated)*
74
gluconeogenesis happens where?
what are the 4 irreversible enzymes needed?
primarily the **liver**
-can also occur in the **kidney** and **intestinal epithelium** if need be because they have enzymes
**P**athway **P**roduces **F**resh **G**lucose
* **p**yruvate carboxylase
* **p**hosphoenolpyruvate carboxykinase
* **f**ructose 1,6 bisphosphate
* **g**ucose 6 phosphate
75
which two actors work together during the fasting state to increase energy supply in the body
-how do they do this
glucoagon and epinephrine work together
* @ adipocytes, epi (\>) glucoagon will stimulate "hormone sensitive lipase" adipocytes --\> stimulate triglyceride breakdown into FA for energy
* @ the liver (epinephrine can also do this on M) will inc cAMP --\> PKA--\> glycogen phosphorylase kinase
* = **inc** glycogen --\> **glucose** via glycogen phosphorylase activation
76
thyroid gland tumor with ""spindle cells arranged in small cluseters", amyloid staining, and proliferation of C cells suggest what tumor
releases what?
medullary thyroid carcinoma
releases calcitonin
77
T. cruzi is endemic where
causes what (besides achalasia)
endemic in south america
chagas ds= BIG organs = cardiomegaly, megacolon, mega-esophagus
78
what 5 things attrach neutrophils to a site of injury
* IL-8,
* C5a,
* LTB4,
* kallikrein,
* platelet activating factor
79
gross changes seen with C. dfi infection
pseudomembranous colitis via toxins A (enterotoxin) and B (cytotoxin)
80
deficiency of what will result in repeated neisseria infections
terminal complement! (C5-C9)
81
clusters of umbilicated papules seen in clusters on a kid suggest what infection
umbilicated = buzzword
poxvirus molluscus contagiosum
(MC= kids, but can be an STD in adults)
82
asplenia (functional or real) increases risk of infection from what
encapsulated organisms
i.e. strep pneumoa, H influ b, N. meningitidis
83
describe the three levels of burns to the skin
**First**-degree burns affect **only the outer laye**r of the skin. They cause pain, redness, and swelling.
**Second**-degree burns affect both the **outer and underlying layer of skin**. They cause pain, redness, swelling, and blistering. They are also called partial thickness burns.
**Third-**degree burns affect the d**eep layers of skin**. They are also called full thickness burns. They cause white or blackened, burned skin. The skin may be numb."
84
how to read labs quickly to see if its SIADH
SIADH = low Na, and plasma osmolality \< urine osmol
85
best test to confirm hyperthyroid
T FOUR LEVELS
T4
86
what is the characteristic difference between a low grade dysplasia and a malignancy
low grade dysplasia is still reverisble
carcinoma in situ/high grade dysplasia and malignancy are IRreversible
low grade dysplastia already has
* inc mitoses
* disordered maturation
* loss of cell polarity
* nuclear abnormalities
* pleomorophism (change in cell shape)
87
extensor reflex of the toes =
aka babinski reflex
UMN lesion
88
what lab finding is the marker for infectivity for hepatitis
the HX**e**Ag
- high eAg = high infectivity
- low eAg with
89
what is the effect of decreased 2,3 BPG binding on the function of Hgb
* which Hgb subtype acts this way
* what disease is this associated with
*
dec 2,3 BPG binding --\> inc affinity for O2 --\> drop off less O2 to tissues
* HbF does this so that the fetus can get enough of the left over O2 from mom's blood
* can also be seen in familial erythrocytosies (benign condition with mutated erythrocytes --\> inc in erythrocyte production to make up for it)
90
when can FAs not be beta oxidized in the mitochondria?
what is their fate?
-this pathway is linked to what congenital disorder that presents how
**VLCFA** (very long chain FAs) and **branched -chain fatty acids** cannot be beta-oxidized
* must be broken down by the peroxisomes
**Zellweger Syndrome**
* abn cranial bones (large anterior fontanelle, widely splayed cranial sutures...)
* hepatomegaly
* neuro defects (seizures, hypotnoia)
* will die within months of birth
91
what is the function of the TCA cycle
which other pathways feed into it
* failure of the TCA cycle for any reason will change the levels of the following in what direction
* urine propnyl coA
* serum glucose
* serum ketone bodies
* serum ammonia
The TCA cycle takes the end products of other cycles and gets ATP out of them
* GLYCOLYSIS (pyruvates--\> acetyl CoA : acetyl CoA is the starting point of the TCA cycle)
* BETA OXIDATION of odd numbered FA (proponyl CoA--\> methymalonyl CoA --\> succinyl CoA-=: S-CoA enters the cycle)
* PROTEIN catabolism / AA breakdown
* some AAs/byproducts of protein catabolism will enter the TCA cycle as substrates
* leucine, isoleucine, lysine, phenylalanine, tryptophan, and tyrosine, are converted into acetyl-CoA which either enter the cycle OR form ketone bodies
* x TCA cycle
* inc proponyl CoA
* sec serum glucose
* no use up the pyruvate to make ATP so you do more glycolysis to at least get ATP out of that
* inc ketone bodies
* acidosis from all the build up of the acids (CoAs) that were supposed to be used in the TCA cycle
* plus the build up in glycoylsis by-products inhibits gluconeogenesis --\> inc ketone bodies
* inc serum ammonium
* build up of the organic acid byproducts of glycolysis will also directly inhibit the urea cycle
92
body nitrogen levels are kept at homeostatic levels by the constant shufflinf of what two players
--what substance in the liver will pick up an amino group from alanine (and really anyone bc it be picking up a lot of amino groups here and there to help out)
--alanine and glutamine(in liver, M, and kidney)--alpha ketoglutarate
93
what pathology can be seen here
thymoma
94
what is the clinical manifestationof a pineal gland tumor and what is the most common type
* obstructive hydrocephalus with dorsal midbrain syndrome
* aqueductal stenosis --\> OH --\> papilledema, HA, vomiting
* Parinaud/dorsal midbrain syndrome =
* 1. limitation of upward gaze (prefer downward)
* eyelid retraction
* light-near dissociation (i.e. pupils that react to light but not to accomidation or vice versa)
95
outline the order of genetic mutations that occur in SPORADIC colon CA
how is it different from an inherited syndromes
**chromosomal instability pathway:**
*_sporadic AND most cases of FAP_*- gotta start from the beginning = start w **_A_**PC gene : "AK-53 firing sequence"
* xAPC --\> makes normal colon into hyperproliferative
* abn methylation + inc COX --\> hyperproliferative into an adenoma
* K-ras activation --\> p53 inactivation --\> adenoma into adenocarcinoma
* etc.
vs Lynch Syndrome=HNPCC
* microsatellite instability pathway = abn mismatch repair genes **_(MLMH1)_**
96
match the following tumor markers with the tumors they are associated with
* alpha fetoprotein
* CA 19-9
* CA 125
* carcinoembryogenic Ag
* human chorionic gonadotropin
* prostate specific Ag
* alpha fetoprotein
* HCC and germ cell
* CA 19-9
* pancreatic
* CA 125
* ovarian
* carcinoembryogenic Ag
* GI- colo*_rectal_*
* human chorionic gonadotropin
* choriocarcinoma, germ cell
* prostate specific Ag
* prostate
97
talk about the diseasees that are suggested by the following lab findings (seperate things)
* inc serum methianine
* dec serum cysteine/adenosine
* inc leucine/isoleucine
* inc valine
* inc phenylalanine
* dec tyrosine
* BOTH inc methianine/ dec cysteine of adenosine suggest a defect in the methionine cycle
* associated w **_homocystinuria_**
* methionine --broken down into --\> adenosine + homocysteine : some of the homocystein (w cofactor B6) will become cysteine, some (w cofactor B12) will revert back to methionie
* homocystinuria will present w child w hypercoag + thromboembolic occlusion
* i.e a young kid w an MI
* --\> acute coronary syndrome , ectopia lentis (ocular lens displacement), + intellectual disability
* MC cause = xcystathionine synthase --\> hypermethionine
* BOTH inc leucine/isoleucine or inc valine
* associted w maple syrup urine ds
* x branched chain alpha-ketoacid dehydrogenase (can't break down these branched AAs)
* present as: dif feeding, seizures, cerebral edema, sweet odor of urine
* BOTH inc phenylalanine/ dec tyrosine
* PKU = phenylketonuria
* x phenylalanine hydroxylase = no convert Ph --\> tyrosine
* intellectual disability if left untreated, can treat tho (w diet and/or supplement)
98
what is the difference between DNA polymerase I and III
99
what are the three CAs associated w VHL
100
101
embryologic failures that lead to cleft lip vs cleft palate
cleft lip: x fusion of maxiallary prominence and intermaxillary segment
cleft palate: x fusion of palatal processes
102
which cell metabolic pathways occur in
* the mitochondria
* the cytosol
* both
* the mitochondria
* beta oxidation of fatty acids
* TCA cycle
* pyruvate carboxylation (also the first step in gluconeogenesisi)
* the cytosol
* glycolysis
* fatty acid synthesis
* pentose phosphate pathway
* both
* urea cycle
* gluconeogenesis
* heme synthesis
103
basophilic stippling of RBCs is seen in what condition
clinical presentation? pathophys?
104
which steps of gluconeogenesis and the TCA cycle produce GTP
105
what disease results from the x(hypoxanthine-guanthine-phosphoribosyltransferase)
-clin presentation
xHGPRT = Lesch Nyhan Syndrome
106
which signalling proteins in the cell lead to differentiation of the cell? which lead to DEdifferentiation?
107
which receptors, and drugs, affect pupil constriction and dilation
108
109
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