4 and 5 star items Flashcards
1
Q
Neural Crest Derivatives
A
MAGIC COPS
Melanocytes Aortic pulmonary septum Ganglia - autonomic, dorsal root, enteric - Peripheral nervous system Iris stroma Chromatin cells (adrenal medulla) Cranial nerves Odontoblasts/Ossicles Parafollicular (C) cells Sclerae
2
Q
Whiteboard derivatives of arachidonic acid and pharmacologic inhibitors
A
Page 15 DIT workbook
3
Q
Label circle of willis worksheet
A
answers page 38 DIT workbook
4
Q
Gertsmann syndrome
A
lesion of DOMINANT angular gyrus of parietal lobe
agraphia - can’t write
acalculia - can’t do math
Right -left disorientation
Finger agnosia - can’t distinguish fingers
5
Q
Hemispatial neglect syndrome
A
lesion to NONDOMINANT angular gyrus of parietal lobe
Neglect body or surroundings contralateral to lesion
6
Q
Symptoms of lateral medullary syndrome (Wallenberg Syndrome)?
A
Loss of pain and temp over contralateral body - spinothalamic tract
Loss of pain/temp over ipsilateral face - spinal trigeminal nucleus damage
Hoarseness, difficulty swallowing, loss of gag reflex - nucleus ambiguus, CN IX and X damage
Ipsilateral Horner syndrome - descending sympathetic tract
Vertigo, nystagmus, N/V - vestibular nuclei damage!
Ipsilateral cerebellar defects - ataxia, past pointing - inferior cerebellar peduncle damage - spinocerebellar tract
Assoc w/ PICA occlusion
7
Q
Medial medullary syndrome
A
contralateral spastic hemiparesis - pyramid/corticospinal tract damage
Contralateral tactile and kinesthetic defects - medial lemniscus damage
Tongue deviates toward side of lesion - hypoglossal nucleus/nerve damage
Pain and temp preserved
Assoc w/ anterior spinal a. occlusion
8
Q
Lateral inferior pontine syndrome
A
ipsilateral facial nerve paralysis - facial nucleus and fiber damage
Ipsilateral limb and gait ataxia - damage to middle cerebellar peduncle
Ipsilateral loss of pain and temp from face - spinal trigeminal nucleus and nerve damage
contralateral loss of pain/temp - damage to spinothalamic tract
Ipsilateral Horner Syndrome - damage to descending sympathetic tract
No contralateral body paralysis or loss of light touch/vibratory/proprioceptive sensation
Assoc w/ AICA occlusion
9
Q
Medial pontine syndrome
A
Contralateral spastic hemiparesis - corticospinal tract
Contralateral loss of light touch/vibratory/proprioceptive sensation - ML damage
Ipsilateral INO - MLF damage
Gaze away from side of lesion - PPRF
Ipsilateral paralysis of LR m. - damage to abducens nucleus
Pain and temp preserved
Basilar A - median and paramedian branches occluded
10
Q
Weber Syndrome
A
occlusion of paramedian branches of PCA
Cerebral peduncle lesion:
- dysphagia, dysphonia, dysarthria - corticobulbar tract
- Contralateral spastic hemiparesis - corticospinal tract
Oculomotor n. palsy –> ipsilateral ptosis, pupillary dilation, lateral strabismus (down and out)
11
Q
Tension Headache
A
Constant, non-throbbing pain - hours to 7 days
Frontal or occipital regions (b/l) or as band around head
No associated sx like photo/phono-phobia, auras, n/v, focal neurologic change
Tx: NSAIDs, Acetaminophen
12
Q
Migraine Headache
A
At least 5 attacks
Lasts 4-72 hours (2-48 in kids)
At least 2 of the following: u/l location, throbbing, pulsating quality, moderate to severe intensity (inhibits/prohibits daily activities), aggravated by routine physical activity
At least one of the following: N/V, photo- and/or phono-phobia
Tx: Triptans (sumatriptan, rizatriptan, zolmitriptan): serotonin agonists –> vasoconstriction, modulates neurotransmission in CN V
CONTRAINDICATED in CAD, prinzmedal angina, pregnancy
13
Q
Cluster Headache
A
Strictly unilateral
Severe piercing/boring pain in periorbital/retroorbital region
does not throb like migraine, no aura
15 min - 3 hours, daily at same time, continues for 4-8 weeks
May be associated w/:
Partial Horner syndrome - ptosis, miosis
Ipsilateral eye redness, tearing, rhinorrhea, nasal congestion
Tx: 100% O2 in nonrebreather mask for 15 minutes
Can also use triptans, NSAIDs, Acetaminophen
14
Q
Alzheimer Disease
A
Tau neurofibrillary tangles
Senile plaques - Abeta extracellularly
Early onset: Presenilin 1,-2; Amyloid precursor protein (APP) on Chr 21 (why Downs get it in 40s)
late onset: ApoE4 –> beta sheets
Tx: Slow down progression
- AChEI: Donepizil, Galantium, Rivastigmine
- NMDA receptor antagonist: Memantine -decreases excitotoxicity
15
Q
Vascular Dementia
A
White matter ischemic changes on MRI
d/t atherosclerosis
16
Q
Dementia w/ Lewy Bodies
A
alpha synuclein protein
Parkinsonian features
Visual hallucinations
Syncopal episodes = falls
17
Q
Frontotemporal dementia
A
aka Picks
Tau on silver stain - pick bodies
atrophy of frontal/temporal lobes
Dementia + behavior/personality changes - more crass
Demential + progressive aphasia - can’t understand what is being said to them
18
Q
Creutzfeldt-Jakob Disease
A
RAPIDLY progressing demential - weeks-months
personality change
muscle spasms
myoclonus
PrpSc - beta pleated sheets –> spongiform encephalopathy
19
Q
Work up for Alzheimers
A
RPR - r/o neurosyphilis
HIV
B12 levels
If dysarthria and liver dz present think Wilsons
TSH - r/o hypothyroidism
MRI to look for normal pressure hydrocephalus, vascular dementia
Screen for depression in elderly - will recognize problem
20
Q
Causes of Delirium
A
UTI, infections, fevers
Drugs: bentos, anticholinergic side effects, withdrawal or drug abuse
hypoxemia
electrolyte imbalance
21
Q
Delirium vs dementia: Onset, Daily course, consciousness, thought, psychotic, prognosis
A
Onset: Delirium acute (hours to days), Demential gradual (mo-yrs)
Daily course: Delirium fluctuates, dementia consistent
Level of consciousness: Delirium decreased arousal, demential normal
Thought production: delirium disorganized thinking, flight of ideas; dementia impoverished
Psychotic features: delirium visual hallucinations, delusions; dementia - minimal
Prognosis: delirium - reversible, dementia - irreversible
22
Q
Location/function of Muscarinic receptors
A
M1: enteric NS
M2: heart - decreases contractility, lowers HR via SA node
M3: increase bladder contraction, increase gut peristalsis, lacrimation, mitosis, bronchoconstriction
23
Q
Epi/NE receptor functions
A
a1 - vascular sm.m. constriction - vasoconstriction
a2 - inhibit NE release
b1 - increase HR, contractility
b2 - vasodilation, bronchodilation
24
Q
Dopamine receptor function/location
A
D1 - relax renal vascular sm.m.
D2 - brain
25
Histamine receptor function
H1: nasal secretion, bronchial mucus production, pruritic, bronchoconstriction
H2: increase gastric secretion
26
Vasopressin receptor function
V1: vascular sm.m. contraction
V2: increase reabsorption in collecting tubules of kidney
27
Gq activation cascade
Phosphorylase C --> PIP2
1. IP3 increases Ca2+
2. DAG activates PKC
"Cutesies HAVe 1 M and M"
Q-C
H1, a1, V1, M1, M3
28
Gs activation cascade
stimulate adenylyl cyclase --> increased cAMP - activates PKA
"everything else" - B1, B2, D1, H2, V2 - need other mnemonics
29
Gi cascade
inhibits adenylyl cyclase --> decreased cAMP and less activated PKA
MAD 2s
M2, a2, D2
30
Draw Michaelis-Menton and Lineweaver Burk plots for competitive, noncompetitive and no inhibition
Page 136-137
31
How does a competitive inhibitor impact Vmax and Km?
no change to Vmax, shifts right as increases Km
it's competitive, takes longer to hit Vmax because it has to compete with the inhibitor
32
How does noncompetitive inhibitors impact Vmax and Km?
decreases Vmax, does not change Km
33
Write out the 4 pharmacokinetic equations
Vd = D/C
Cl= 0.7xVd/t1/2
LD: Css x Vd
MD: Css x Cl
34
how does potency and efficacy change with competitive and noncompetitive antagonists compared to full agonists?
Competitive: takes longer to reach same efficacy. Same efficacy, decreased potency
Noncompetitive: lower max effect, efficacy decreases
35
How do partial agonists change potency and efficacy compared to full agonist?
partial agonists have lower efficacy than a full agonist
Potency is independent of efficacy. Can be increased or decreased.
36
How do you calculate therapeutic index and what is the significance?
LD50: lethal dose to 50%
ED50: efficacy dose to 50%
TI = LD50/ED50
You want a high index or wide therapeutic window. need higher dose to kill someone OR the effective dose is small enough there is less chance of toxicity.
Wide window or high index = safer drug
37
Some Drugs With Low Therapeutic Index
```
Seizure drugs
Digoxin
Warfarin
Lithium
Theophylline
```
38
Tetralogy of Fallot
1. RV outflow obstruction - pulmonic stenosis
2. RV hypertrophy
3. VSD
4. Overriding aorta
"IHOP"
R to L may be intermittent and have mostly L to R = cyanotic
Crying, feeding, increased activity = R to Left = cyanotic
Squatting relieves cyanotic sx, increase systemic resistance forces L to R shunt
Boot shaped heart on CXR
39
Cardiac Output: equation and what increases or decreases it
SV X HR
Increased:
Exercise, increased HR (to a point)
Increased contractility - Catecholamines
Decreased:
B1 blockers
HF, acidosis, hypoxia, hypercapnia
Non-dihydropyridines - verapamil
40
Fick principle
CO = rate of O2 consumption/(arterial O2 - venous O2 content)
41
Mean arterial pressure (MAP)
P=QR MAP=(CO) x (peripheral resistance)
MAP = 2/3 diastolic + 1/3 systolic at resting HR
42
Pulse pressure
Systolic pressure - diastolic pressure
Increase SV increases pulse pressure
43
Ejection fraction
SV/EDV
Decrease in systolic HF
Increased in increased contractility
Normal 55-70%
44
Illustrate the Starling Forces affecting capillaries
page 177
45
Conditions causing increased hydrostatic pressure in capillaries
increased central venous pressure - CHF
venous thrombosis
compression of vein
sodium/water retention
46
Conditions decreasing oncotic pressure in capillaries
liver dz
protein malnutrition
nephrotic sn
protein losing enteropathy
47
Conditions increasing capillary permeability (Kf)
septic shock
toxins
burns
48
conditions increasing oncotic pressure of interstitium
lymphatic obstruction
| -tumor, inflammation, surgery, radiation
49
Draw out the changes seen in pressure-volume loops with increasing after load, preload, and contractility.
page 181
50
S1 sound
M and T close
51
S2 sound
A and P close
Splitting on expiration never normal - pulmonic stenosis, RBBB
Fixed splitting - ASD
Paradoxical splitting - AS, LBBB
52
Bedside maneuvers changing mumurs
Inhale - increases tricuspid M
Exhale - increases mitral M
Hand grip - louder mitral regurgitation
Valsalva - most get softer, makes hypertrophic cardiomyopathy M louder
53
Aortic regurgitation
Early Diastolic M, decrescendo
Wide pulse pressure
Water hammer pulse - strong bounding peripheral pulses
Head bobbing
Causes:
Dilation aortic root - tert syphilis, marfans
Bicuspid aortic valve
Rheumatic fever
54
Mitral Stenosis
Diastolic M - opening snap
enhanced by expiration
Cause:
Rheumatic HD
--> L atrial dilation
55
Mitral regurgitation
Holosystolic M
Radiates to left axilla
Increased in hand grip, squatting
```
Causes:
Rheumatic heart dz
endocarditis
ischemic heart dz
LV dilation - separate valve leaflets
Mitral valve prolapse
```
56
Tricuspid regurgitation
Holosystolic M
Louder w/ inspiration - distinguishes from MR
Cause:
Rheumatic heart dz
endocarditis - IV drug users
57
Ventricular septal defect murmur
holosystolic M - left sternal border by T
| NEWBORNS!
58
Aortic Stenosis
Systolic M w/ ejection click, crescendo, decrescendo
Radiates to carotids
Weak, delayed peripheral pulses --> syncope
angina, dyspnea
59
What causes the dicrotic notch in the pressure tracing of the cardiac cycle?
elasticity of the aorta causes increase in pressure as the valve closes - dips is the back flow as the valve closes and the coronary artery fills
60
What accounts for the a, c, and v waves in the atrial pressure (aka venous pulse)?
a: Atrial contraction against an increasing ventricle pressure
c: Ventrical contraction causes valves to bulge into atria
v: filling against closed M/T valves
61
When does the isometric contraction fall in the cardiac cycle?
between the AV valves (M/T) closes - S1 heart sound
| and the aortic valve opens
62
When does isometric relaxation fall in the cardiac cycle?
between Aortic valve closing - S2 heart sound
| and AV valves (M/T) opening
63
What is happening in the heart during diastole? What are the phases called
1. Isometric relaxation
2. rapid flow
3. diastasis
4. atrial systole
64
S3 heart sound
early-mid diastole during rapid ventricular filling
Common in dilated ventricles - dilated cardiomyopathy, CHF
Mitral regurg
L to R shunt - VSD, ASD, PDA
Normal in kids and pregnant women (increased preload)
65
S4 heart sound
right before S1
atrial kick
high atrial pressure in ventricle hypertrophy
- hypertrophic cardiomyopathy
- aortic stenosis
- chronic HTN w/ LVH
- post MI
66
What causes a normal splitting of S2?
Inhalation - decreases intrathoracic pressure which sucks blood into the RA, increases preload to RV
More to push out causes slight delay in pulmonic valve closure
67
What causes wide splitting S2?
expiration splitting of S2 is never normal
| caused by pulmonic stenosis, RBBB
68
What causes paradoxical splitting of S2?
aortic stenosis, LBBB
P2 delay - improved in inspiration
69
What causes fixed splitting of S2?
atrial septal defects - more blood into R heart through L to R shunt
slower expel of blood from RV and closure of pulmonic valve
70
What heart sounds/murmurs are heard better in the left lateral decubitus position?
MS, MR, left-sided S3, S4
71
Draw out the diastolic heart murmurs
page 185
72
Draw out the systolic heart murmurs
page 188
73
Osteoporosis
Increased resorption of bone, decreased osteoblast activity
Prone to fx, spinal compressive fx --> increased kyphosis
Dx w/ DEXA scan
Tx:
stop smoking, stop steroids if able, increase exercise
Ca/vit D supplementation
Bisphosphonates (inhibit osteoclastic resorption, risk erosive esophagitis, osteonecrosis of jaw)
Conjugated estrogen
SERM (raloxifen)
Teriparatide (pulsatile injections not to exceed 2 yrs)
Denosumab (RANK-L inhibitor)
74
Serum Ca2+, Serum phosphate, alk phos and PTH levels in osteoporosis
all normal
75
Serum Ca2+, Serum phosphate, alk phos and PTH levels in osteopetrosis
generally normal, can have slight increase in PTH and alk phos (osteoblast activity marker) and slight decrease in Ca2+
76
Serum Ca2+, Serum phosphate, alk phos and PTH levels in paget disease
increased alk phos, rest normal
77
Serum Ca2+, Serum phosphate, alk phos and PTH levels in rickets/osteomalacia
Vit D deficiency --> decreased serum Ca2+, which increases PTH that dumps serum phos into urine (so decrease serum phos), alk phos is either normal or slightly increased
78
Serum Ca2+, Serum phosphate, alk phos and PTH levels in Renal insufficiency
Can't activate VitD --> decreased serum Ca2+, increased PTH, but kidney can't dump phosphate so increased serum phos and alk phos is either normal or increased
79
Serum Ca2+, Serum phosphate, alk phos and PTH levels in Vit D intoxication
Serum Ca2+ high, PTH low, Serum Phos high, alk phos normal
80
Serum Ca2+, Serum phosphate, alk phos and PTH levels in Primary hyperparathyroidism
High PTH, increases serum Ca2+ and alk phos, low serum phos
81
Serum Ca2+, Serum phosphate, alk phos and PTH levels in osteitis fibrosa cystica
Caused by high PTH:
high PTH, high serum Ca2+, low serum Phos, high alk phos
82
Hand manifestations of RA
Swan neck deformity - PIP hyperextension w/ compensatory flexion of the DIP
Boutonniere deformity - flexion contracture of the PIP and extension of the DIP
83
Wrist manifestations of RA
radial deviation at the wrist with ulnar deviation of the digits
Deformity resulting in median n. entrapment - carpal tunnel syndrome
84
Elbow manifestations of RA
flexion contractures
85
Knee manifestations of RA
synovial hypertrophy w/ chronic effusion and ligamentous laxity
86
Posterior knee manifestations of RA
Popliteal (Baker's) cyst- extension of the inflamed synovium into the popliteal space
87
Ankle, forefoot, subtalar manifestations of RA
deformities, pain w/ ambulation
88
Upper cervical spine manifestations of RA
Atlantoaxial subluxation
89
Location of rheumatoid nodules
olecranon bursa
proximal ulna
achilles tendon
occiput
90
Gout crystals
monosodium urate
| needle shade crystals, negatively (yellow) birefringent
91
Causes of gout
decreased excretion of uric acid - thiazide or loop diuretics
increased production of uric acid: purine-rich foods, Lesch-Nyhan syndrome, tx for leukemia or lymphoma (increased cell turnover)
Dietary excess
Alcohol consumption - competes w/ uric acid excretion sites in kidney
92
Presentation of gout
asymmetric joint inflammation, inflammation in first MTP (podagra)
Top - ear, tendons, bursa - not tender
93
Most common forms of skin cancer
1. basal cell
2. squamous cell
3. melanoma
94
Order of metastatic risk of most common forms of skin cancer
1. melanoma
2. squamous cell
3. basal cell
95
Squamous cell carcinoma
sun exposed areas
locally invasive
ulcerative red lesion
Histo: keratin pearl
96
Basal cell carcinoma
sun exposed areas
Rolled edge appearance, central ulceration, pearly papule appearance w/ telangectasias
micro: palisading nuclei
97
Melanoma
```
S100+
sun exposed areas
Depth of tumor correlates w/ risk of mets
-excisional w/ margins
-punch bx - full thickness
```
Micro: nests of melanocytes fill dermis, obscure epidermal border as goes into epidermis
```
ABCDs:
Asymmetry
Border irregular
Color - multiple
Diameter >pencil head
```
98
Homolog of glans penis
glans clitoris
99
Homolog of corpus spongiosum and corpora cavernosa
vestibular bulbs
100
Homolog of bulbourethral (Cowper) glands
greater vestibular (Bartholin) glands
101
Homolog of prostate gland
urethral and paraurethral (Skene) glands
102
Homolog of ventral shaft of penis
labia minor
103
Homolog of scrotum
labia majora
104
Female genitalia development pathway
No mullerian inhibitor factor = paramesonephritic ducts become fallopian tubes, uterus, upper vagina
No testosterone = mesonephric duct degenerates
No DHT= urogenital sinus becomes lower vagina
105
Male genitalia development pathway
SRY gene on Y Chr - testis determining factor:
1. Sertoli cell development and secretion of mullerian inhibitory factor
- paramesonephric (mullerian) duct degenerates
1. Leydig cells secrete testosterone --> mesonephric duct becoming internal genital structures (except prostate)
5-alpha-reductase converts T into DHT
--> urogenital sinus becomes external genital structures and prostate
106
PCOS diagnostic criteria
2 of 3:
-oligo/an ovulation - menstrual irregularity, infertility
Hyperandrogenism - acne, hirsutism
Polycystic ovaries on US - string of pearls sign
Assoc sx: obesity, insulin resistance, infertility
107
Cancer risk associated with PCOS
increases risk of endometrial hyperplasia and cancer
108
Hormonal abnormalities in PCOS
Increased LH:FSH >2:1
Increased insulin
Increased estrone
Decreased sex hormone binding globulin (SHBG)
109
Cause of increased androgens in PCOS
LH:FSH >2:1
-LH stimulates theca cells to produce androstenedione, FSH does not stimulate granulosa cells to the same extent, not all can be converted to estradiol --> increased androgens
Increased insulin d/t insulin resistance - insulin stimulates theca cells to produce androstenedione --> androgens
Androgens and insulin suppress liver production of sex hormone binding globulin (SHBG) --> increased circulating free hormones (estrogen and androgens)
110
Cause of increased estrone in PCOS
Peripheral conversion of androgens to estrone in adipose tissue
prevents normal ovulatory cycle, stimulates endometrium
SHBG decreased --> increased free hormone circulating
111
Tx of PCOS
Diet/exercise - wt loss to reduce estrone production
OCPs
Cyclic prostestins
hirsutism:
Spironolactone -inhibits steroid binding
Ketoconazole - inhibits steroid synthesis by blocking desmolase
Metformin - insulin resistance
Clomiphene - SERM for anovulation
112
Klinefelter Syndrome
47, XXY - have barr body
Testicular atrophy = decrease in T, less muscle mass, less facial/body hair, broader hips
Tall, longer extremities, gynecomastia, female hair distribution
Reduced fertility - dysgenesis of seminiferous tubules - decreased inhibin, increased FSH
113
Turner Syndrome
MC cause of primary amenorrhea
45, XO - no barr body
Short stature, shield chest, low hairline, low set ears, webbing of neck (cystic hygroma)
gonadal dysfunction - streak ovaries = amenorrhea, infertility
Bicuspid aortic valve, coarctation of aorta
horseshoe kidney
decreased estrogen --> Increased LH and FSH
114
Label brachial plexus
page 91
115
Long thoracic N.
innervates serrates anterior m. - holds scapula on thorax
116
Supra scapular n.
innervates:
infraspinatus - externally rotates humerus, stabilizes joint
supraspinatus m. - abducts arm
117
Lateral pectoral N.
innervates pectoralis m. - flexion, adduction, medial rotation of humerus
118
Upper scapular N.
subscapularis m. - internally rotate arm
119
Thoracodorsal N.
Latissimus dorsi m. - extension, adduction, transverse extension, flexion from extended position and internal rotation
120
Lower sub scapular N.
teres major - medially rotates and adducts arm
121
Musculocutaneous N
biceps, coracobrachialis, branchialis m. - main flexors of arm
122
Axillary N.
deltoid - abduct in frontal plane
| teres minor - laterally rotate humerus
123
Radial N.
extensors and triceps - extend forearm
injury --> wrist drop
124
Median N.
pronators and thenar m. of hand - pronate forearm
125
Ulnar N.
interosseous, hypothenar m of hand, flexor carpi ulnas m.
| flex and adduct hand
126
Erb duchenne palsy
Waiter's tip
Lesion of the superior trunk (C5-C6) - bruising, stretching, or tearing (permanent) of N.
Trauma - shoulder/neck d/t shoulder dystocia or clavicle fracture in birth
damage to supra scapular N., musculocutaneous n., axillary n.
complete or partial paralysis of UE
Adducted, medially rotated, pronated forearm
127
Klumpke's palsy
Lesion of inferior trunk (C8-T1)
traction of abducted arm
paralysis/atrophy of intrinsic m. of hand - hypothenar/thenar, interosseous m.
+/- wrist/finger flexors
Sensory defects - medial arm, forearm, hand
Severe: supination of forearm w/ wrist and fingers flexed
128
Lymphatic draining of arm, lateral breast
axillary nodes
129
Lymphatic draining of posterior calf, dorsolateral foot
popliteal nodes
130
Lymphatic draining of thigh
superficial inguinal nodes
131
Lymphatic draining of stomach, upper duodenum
celiac nodes
132
Lymphatic draining of lower duodenum, jejunum, ileum, proximal 2/3 of colon
superior mesenteric nodes
133
Lymphatic draining of distal 1/3 of colon, upper rectum
inferior mesenteric nodes
134
Lymphatic draining of lower rectum (bladder, cervix, prostate too) (above pectinate line)
internal iliac nodes
135
Lymphatic draining of anal canal (below pectinate line)
superficial inguinal nodes
136
Lymphatic draining of testes, ovaries, uterus, kidneys
para-aortic nodes
137
Lymphatic draining of scrotum, vulva
superficial inguinal nodes
138
Lymphatic draining of right arm and right half of head? Rest of body?
right lymphatic duct
| Thoracic duct to junction of left subclavian v/l internal jugular vain
139
Antibody structure
Fab - antigen binding region
-idiotype
2 light chains, 2 heavy chains
Fc - constant region, heavy chains only
- carboxy terminal
- compliment binding
- recognized by CD16 on NK cells
- determines isotypes
140
Ab heavy chains
```
mu - IgM
delta - IgD
gamma - IgG - (gamma 2 lambda 2 or gamma 2 kappa 2)
alpha - IgA
epsilon - IgE
```
141
Ab light chains
```
lambda and kappa
2 kappa:1 lambda normally
-ratio important in dx multiple myeloma
-proliferation of 1 malignant plasma cell produces all same Ab
-ratio will skew
```
142
Circulating IgG
```
Most abundant in blood
delayed secondary immune response
fixes complement
crosses placenta
opsonizes bacteria
binds/neutralizes viruses and bacteria toxins
```
143
Circulating IgA
mucous membranes and Gi tract - MALT
monomer in circulation
secretory IgA is a dimer (end to end) - GI tract, tears, mucus, saliva, breast milk
144
IgA to lumen
transcytosis
| -as it passes through cells, picks up secretory component that protects the dimer from gastric acid
145
Circulating IgE
parasite immunity by activating eosinophils
bind receptors on mast cells and basophils
--> cross linking --> degranulate
Type I hypersensitivity reaction - allergies
146
IgM
surface of B cells - monomer
circulation - pentamer
primary immune response - early
-used as a marker for acute illness
does not cross placenta
147
IgD
surface of B cells
| low level in serum
148
V(D)J recombination
Rearrangement of DNA segments:
- variable (V)
- diversity (D)
- joining (J)
rearrangement begins w/ dsDNA breaks at recomination signal sequences (RSSs) that flank V, D, J coding regions
V(D)J recombination initated by recombination activating gene complex (RAG-1 and RAG-2)
-RAG-1 and RAG-2 recognize RSSs
Mutations in RAG genes --> inability to initiate VDJ rearrangements
--> arrest B and T cell development
149
Anti-IgG Antibodies
aka rheumatoid factor
| RA - nonspecific
150
Anti-citrullinated protein Ab (ACPA)
RA - specific
151
Antinuclear antibodies (ANA)
SLE - nonspecific
152
Anti-Smith
SLE - specific
153
Anti-dsDNA
SLE renal disease
154
Anti histone
Drug induced lupus "SHIPP"
155
Anti centromere
CREST scleroderma (limited)
156
Anti-Scl-70
aka anti-DNAtopoisomerase
| Diffuse scleroderma
157
Anti-Jo-1
Polymyositis/dermatomyositis
158
Anti SSA (anti Ro)
Sjogrens
159
Anti SSB (anti La)
Sjogrens
160
Anti-U1-RNP (Ribonucleoprotein)
mixed connective tissue disease
161
Anti-desmoglein
pemphigus vulgaris
162
Anti-acetylcholine receptor
myasthenia gravis
163
Anti-endomysial (anti tissue transglutaminase)
celiac disease
164
Anti-gliadin
celiac disease
165
Anti-mitochondrial
primary biliary cholangitis
166
Anti-smooth muscle
autoimmune hepatitis
167
Anti-glutamate decarboxylase
T1DM
168
Anti-thyrotropin reeptor
graves dz
169
antithyroid peroxidase (anti TPO)
hashimoto thyroiditis
170
Antithyroglobulin
hashimoto thyroiditis/graves dz
171
anti-basement membrane
good pasture syndrome
172
c-ANCA (PR3-ANCA)
granulomatosis w/ polyangitis "wegners"
173
p-ANCA (MPO-ANCA)
pauci-immune crescentric glomerulonephritis
churg-strauss syndrome
microscopic polyangiitis
174
Type I Hypersensitivity Reaction
IgE, mast cells, basophil mediated
Free Ag binds IgE on presensitized mast cells and basophils
Release of preformed granules of histamine and bradykinin
- -> vasodilation
- -> increased vascular permeability
wheal and flare reaction - utricaria "hives"
Rapid
Anaphylaxis
Atopic disorders - asthma, eczema, allergic rhinitis
175
Type II hypersensitivity Reaction
Ab against cellular Ag
Complement mediated damage
M0 phagocytosis
NK cell destruction
```
Autoimmune hemolytic anemai
acute hemolytic transfusion reaction
Erythroblastosis fetalis - IgG of mom attacks fetal RBCs
Immune thrombocytopenia (ITP) - attack platelets
Pernicious anemia - Ab against IF
Myasthenia gravis
Guillian Barre syndrome - Ab against schwann cells
Graves dz
Pemphigus vulgaris
Bullous pemphigoid
Good pastures Sn
Acute Rheumatic fever
```
176
Type III hypersensitivity reaction
Ab-Ag complexes
Ab against soluble Ag --> complex deposition in tissues
activation of complement
recruit of N0
SLE, RA
polyarteritis nodosa
post strep GN
serum sickness - Ab mediated drug reaction
Arthus reaction - 4-12 hours after injection - locally deposited complexes
177
Type IV hypersensitivity reaction
delayed, cell mediated
T cells bind Ag --> cytokines
--> M0 activation, tissue damage
```
PPD
Poison ivy --> contact dermatitis
hashimoto thyroiditis
MS
graft vs host disease
```
178
Thymic aplasia
DiGeorge
3rd and 4th pharyngeal pouches fail to develop
- no thymus --> no mature T cells
- no parathyroids --> low PTH --> hypocalcemia and tetany (positive Chvostek and Trousseau signs)
Recurrent viral, fungal, protozoal infections
congenital defects in heart, great vessels
90% have 22q11 deletion - detect with FISH
179
Chronic mucocutaneous candidasis
t cell dysfunction vs C. albicans
tx: ketoconazole
180
IL12 receptor deficiency
produced by M0 to Th0-Th1
mycobacterial and fungal infections
181
Bruton agammaglobulinemia
X linked (boys)
B cell deficiency --> defective tyrosine kinase gene --> low levels of all Igs
recurrent bacterial infections after 3-6 mo old - protected by mom's IgG
182
Selective immunoglobulin deficiencies
IgA deficiency MC
- most appear healthy
- sinus and lung infections
- 1/600 European descent
- Assoc w/ atopy and asthma
- possible anaphylaxis to blood transfusions and blood products
183
Severe combined immunodeficiency (SCID)
X linked
defect in early stem cell differentiation
Adenosine deaminase deficiency
Last defense is NK cells
Presentation triad:
1. Severe recurrent infections
- chronic mucocutaneous candidiasis
- Fatal or recurrent RSV, VZV, HSV, measles, flu, parainfluenza
- P. jirovecii pneumonia (PCP)
2. chronic diarrhea
3. failure to thrive
no thymic shadow on newborn CXR
184
Ataxia-telangectasia
IgA deficiency and T cell deficiency --> sinus and lung infections
Cerebellar ataxia and poor smooth pursuit of moving target with eyes
Telangectasias of face after 5 yo
Radiation sensitivity - avoid Xrays
Increased risk: lymphoma and acute leukemias
Elevated AFP - after 8 mo of age
Average age of death - 25 yrs
185
Wiskott-Aldrich syndrome
WAITER
- Wiskott
- Aldritch
- Immunodeficiency
- Thrombocytopenia and purpura
- Eczema
- Recurrent pyogenic infections
X linked
No IgM vs bacterial capsular polysaccharides
Low IgM, high IgA
186
Hyper-IgM syndrome
B and T cell issue
Increased IgM - other Ab isotypes decreased
AR --> no CD40 on B cells
X linked --> no CD40 ligand on helper T cells (MC)
187
Chronic granulomatous disease (CGD)
X linked 65-70%
Lack NADPH oxidase --> phagocytes cannot destroy catalase + microbes
Susceptible to S. aureas, aspergillus infections
Tx: prophylactic TMP-SMX and itraconazole
IFN-gamma helpful
188
Chediak - Higashi syndrome
Defective LYST gene - lysosomal transport
Defective phagocyte lysosomes --> giant cytoplasmic granules in PMNs diagnostic
Triad:
- partial albinism
- recurrent respiratory tract and skin infections
- neurologic disorders
189
Hyper-IgE syndrome (Job syndrome)
Mutation in STAT3 gene
- -> impaired differentiation of Th17 cells - recruit N0 to fight opportunistic infections
- -> impaired recruitment of neutrophils
High levels of IgE and eosinophils
triad:
-eczema
recurrent COLD S. aureas abscesses
Coarse facial features: broad nose, prominent forehead (bossing), deep-set eyes, "doughy" skin
Most common: retained primary teeth --> 2 rows of teeth
190
Leukocyte adhesion deficiency syndrome
Abnormal integrins --> inability of phagocytes to exit circuation
delated separation of umbilical cord - couple months
191
Aorta branches - anterior trunks
Celiac - foregut
Superior mesenteric artery - mid gut
Inferior mesenteric artery - hind gut
192
Splenic flexure watershed
affected first w/ systemic hypotension
shock --> ischemia
193
Abdominal CT
Tail of pancreas "tickles" hilum of spleen
IVC to right of aorta
review abdominal CT links on GI5
194
Celiac disease
autoimmune
intolerance of gliadin (gluten and wheat)
Ab to gliadin and tissue transglutaminase
Blunting of villi and microvilli
Impaired absorption
- foul smelling, pale stool
- stunted growth
- failure to thrive
HLA-DQ2, HLA-DQ8
Increased risk of T cel lymphoma, GI cancer, breast CA
195
Crohn's disease (except pharma tx)
Inflammation of "Everything"
- transmural
- mouth to anus
- MC: terminal ileum
Skip lesions
Spares rectum
Assoc: intestinal flora - tx probiotics
Barium swallow : string sign - narrowed lumen d/t inflammation
```
Stricturing
Diarrhea
malabsorption
wt loss
increased risk of colon CA (not as high as UC)
```
Fistulas - enterocolic, enterovasicular, enterovaginal, enterocutaneous
HLA-B27 disorder: arthritis, joint problems
Immunologic problems
Erythema nodosum -painful red SQ nodules on shins
Bx: noncaseating granulomas
196
Treatment of crohn's disease
5-ASA agents: decreased production of PG in lumen; usual initial tx for mild disease
- mesalamine
- Sulfasalazine - SE: malaise, decreased sperm count
Azathioprine or mercaptopurine > methotrexate
Anti-TNF agents - esp if arthritic component
- infliximab
- adalimumab
Steroids +/- abx for acute exacerabations
197
Ulcerative colitis
```
limited to colon
distal --> proximal
continuous (no skip lesions)
ALWAYS affects rectum
Limited to mucosa and submucosa
```
Autoimmune
barium enema: haustra obliterated --> lead pipe appearance
Bx: crypt abscesses, ulcerations and bleeding
Bloody diarrhea (rectum)
Malnutrition
increased risk of colon CA
Assoc w/ primary sclerosing cholangictasia
pyroderma gangrenosum
sacroiliitis, uveitis - HLA B27
```
Tx: salicylates - sulfasalazine
6-Mercaptopurine
Infliximab
TNF-a inhibitors
Colectomy curative
```
198
V/Q mismatch - apex vs base
ventilation/perfusion
Apex of lung: V/Q >1
high ventilation, low perfusion (gravity pulls more blood to base of lung)
-physiologic dead space
Base of lung V/Q less than 1
- perfusion and ventilation both greater at base of lung
- perfusion higher than ventilation
- -> shunting - deoxygenated blood, not enough O2 for all the blood
W/ exercise, pulmonary capillaries dilate --> increased perfusion, V/Q closer to 1 in apex, more uniform between apex and base
199
Conditions when V/Q approaches zero
low ventilation, high perfusion
airway obstruction - pneumonia, pulmonary edema, lung cancer
shunt - blood leaving deoxygenated
Supplemental O2 ineffective - can't get to the alveolia
200
Conditions when V/Q move toward infinity
high ventilation, low perfusion
blood flow obstruction or physiologic deadspace
Supplemental O2 effective
201
Takayasu arteritis
Granulomatous inflammation of arteries off of aortic arch
--> decreased blood flow to head and arms
"pulseless dz"
Poor pulses in extremities
Young Asian females - teens - 20s
elevated ESR
202
Giant cell arteritis (Temporal arteritis)
MC form of vasculitis
Inflammation of branches of external carotid artery - temporal a.
elderly females
SX:
u/l HA
jaw claudication
vision loss d/t occlusion of ophthalmic a. - irreversible
Elevated ESR (can r/o if normal)
palpable tender temporal a. w/ temple wasting
assoc w/ polymyalgia rheumatica (pain and joint stiffness of neck, shoulders, hips, proximal joints)
Dx: temporal a. bx
- multinuclear giant cells
- grnaulomas in adventitia and media of artery
Tx: high dose steroids for several months - taper off
-prevents vision loss
203
Kawasaki disease
"mucocutaneous LN Sn"
Infants, young kids
East Asian
Fever for 5 days "CRASH and Burn"
4 of 5: "CRASH"
Conjunctivitis - b/l non exudative, painless
Rash - trunk
Adenopathy of cervical LN
Strawberry tongue w/ diffuse erythema of mucus membranes, lips
Hands and Feet - erythema or desquamation
Potential of coronary aneurysms --> rupture --> death
thrombus --> MI
Tx:
IVIG
High dose aspirin to prevent thrombosis (exception to no aspirin to kids)
204
Thromboangiitis obliterans (Buerger dz)
small/medium arteries and veins
smokers, male, 40s
intermittent claudication
superificial nodular phlebitis
cold sensitivity
--> pain, gangrene, autoamputation of digits
Tx: stop smoking
205
Polyarteritis nodosa (PAN)
involves kidneys
involves visceral vessels - skin, GI tract, heart
*spares lungs
Abd pain, melena, neuralgias
**Assoc w/ Hep B and Hep C**
- ANCA (+ANCA rules out)
Tx: corticosteroids +/- cyclophosphamide (lets you use lower dose of steroids)
206
Henoch-Schonlein purpura (IgA vasculitis)
MC systemic vasculitis in childhood
50% recent URI
Rash of palpable purpura of butt and legs
Arthralgias - knees
Abd pain d/t intestinal hemorrhage
Renal dz - IgA nephropathy - nephritis, hematuria (Berger's dz)
Temporary, self limiting
207
Eosinophilic granulomatosis w/ polyangiitis (Churg-Strauss Sn)
Giant cells and eosinophils
```
Assoc w/:
asthma
sinusitis
skin lesions
peripheral neuropathy
```
+p-ANCA (MPO-ANCA)
208
Granulomatosis w/ polyangiitis (GPA) aka Wegner's
Triad:
Focal necrotizing vasculitis
Granulomas in lungs (dyspnea, hemoptysis) and upper airway - soft palate, nasal, sinuses, oropharynx
Glomerulonephritis - hematuria
Collapse bridge of nose - saddle nose
+c-ANCA
Tx: cyclophosphamide, corticosteroids
209
Microscopic polyangiitis
Affects lungs
Affects kidneys - Pauci-immune cresentric GN
+p-ANCA
210
Staphylococcus aureus toxins and actions
a-hemolysin/a-toxin --> hemolysis
b-hemolysin/sphingomyelinase --> hemolysis
gamma-hemolysin (leukocidin) --> toxic to leukocytes, hemolysin --> hemolysis
Delta-hemolysin/delta toxin --> toxic to erythrocytes and other cells
Panton-Valentine leukocidin --> tissue destruction w/ MRSA, affects both N0 and M0
Exfoliative toxin --> scalded skin syndrome in newborns w/in 1 wk
-act at zona granulosa of epidermis --> flaccid bullae
SUPER ANTIGENS:
- Enterotoxins --> food poisoning (V/D)
- TSST-1 --> release of cytokines --> TSS (high fever, hypotension, diffuse rash (looks like sunburn))
211
Streptococcus pyogenes toxins and actions
Streptolysin O --> hemolysis (Oxygen labile) - blood agar plates, ASO titer
Streptolysin S --> hemolysis (oxygen Stable)
SUPER ANTIGEN
-Streptococcal pyogenic exotoxins type A, B, C/erythrogenic toxins --> red rash (erythro-) and fever (pyro-) of scarlet fever
Toxic shock like syndrome
(RF is Ab mediated)
212
Yersinia enterocolitica toxins
heat stabile toxin --> increased guanylyl cyclase activity --> increased cGMP
"Pseudoappendicitis" - abd pain
213
Bacillus anthracis toxins
Anthrax toxin:
- Edema factor - increases adenylyl cyclase
- Lethal factor
- Protective antigen
214
Vibrio cholerae toxins
Choleragen - cholera toxin --> increased adenylyl cyclase --> increased cAMP
Cl- and H20 cross into lumen of intestine --> Rice water stools
12-20 L loss of fluid/day --> circulatory collapse
HYDRATE!!!
215
Bordetella pertussis toxin
pertussis toxin - binds and inactivates Gi proteins --> increased cAMP
216
Corynebacterium diphtheriae toxin
Diphtheria toxin inactivates EF2 (elongation factor) --> pharyngitis w/ gray pseudomembranes
Toxin lethal in small quantity - cardiac/neuro
217
Pseudomonas aeruginosa toxin
Exotoxin A inactivates EF2
218
Shigella toxin
Shiga toxin - similar to Ecoli O157:H7
cleave host rRNA at adenine base in 60S ribosomal subunit --> inhibited protein synthesis --> cell death
219
Enterohemorrhagic E. coli (EHEC) toxin
(includes O157:H7)
Verocytotoxin (Shiga toxin)
- -> bloody diarrhea
- -> Hemolytic Uremic Syndrome (HUS): damages renal endothelial cells causing: hemolytic anemia, thrombocytopenia, acute renal failure
220
Enterotoxigenic E. coli (ETEC) toxin
heat labile toxin --> increased adenylyl cyclase --> increased cAMP
heat stable toxin --> increased guanylyl cyclase activity --> increased cGMP
--> watery diarrhea, leading cause of travelers diarrhea
221
Mycoplasma pneumoniae
no cell wall
perosn to person via respiratory droplets
common cause of pneumonia in school aged kids, college students**, military recruits
presentation:
1st: malaise, HA, low grade fever
--> nonproductive cough, diffuse interstitial infiltrates
"walking pneumonia"
CXR: patchy, reticulonodular infiltrates
Dx:
cold agglutinins - IgM lyse RBCs in cold environment
PCR
Serology
Tx: empiric: macrolide - azithromycin, doxycline, fluoroquinolones
222
```
Bacterial meningitis CSF findings:
Opening pressure
WBC count
Differential
Protein
Glucose
Gram stain
```
```
Opening pressure: up
WBC count: markedly increased
Differential: neutrophils
Protein: up
Glucose: down
Gram stain: + 70-80%
```
223
```
TB/fungal meningitis CSF findings:
Opening pressure
WBC count
Differential
Protein
Glucose
Gram stain
```
```
Opening pressure: up
WBC count: up
Differential: lymphocytes
Protein: up
Glucose: down
Gram stain: none
```
224
```
Viral meningitis CSF findings:
Opening pressure
WBC count
Differential
Protein
Glucose
Gram stain
```
```
Opening pressure: normal or up
WBC count: up
Differential: lymphocytes
Protein: normal or up
Glucose: normal
Gram stain: none
```
225
TORCHeS infections
```
Toxoplasmosis
Other: parvo B 19
Rubella
CMV
HIV/HSV
Syphillis
```
Primary infection in pregnancy
- growth retardation
- intelectual disability
- HSM
- miscarriage/still birth
226
Toxoplasmosis
Toxoplasma gondii
Cat feces
undercooked meat
```
Congenital infection
Triad:
chorioretinitis
hydrocephalus
intracranial calcification
```
227
Parvovirus B19
adults - arthritis
kids: erythema infectiosum - fifth's dz - slapped cheek rash
fetus:
infects RBC precursors --> severe fetal anemia
--> high output HF
--> hydrops fetalis: fluid accumulating in different parts of body, ascites, plural effusions
228
Rubella
kids: german measles - mild fever, rash
```
congenital infection:
cataracts
PDA
sensorineural deafness
"blueberry muffin" rash: areas of extramedullary hematopoiesis
```
229
CMV
MC TORCHeS
monolike sn in kids and adults
fetal: jaundice, HSM, sensorineural hearing loss
230
TORCHeS - HIV
transmission prevention
- HAART during pregnancy
- intrapartum zidovudine
- c-section
zidovudine prophylaxis to infant
avoid breast feeding - virus shed in breast milk
231
TORCHeS - HSV
passed via direct contact in delivery
```
congenital:
vesicular rash
conjunctivitis
pneumonia
CNS dz - meningoencephalitis
disseminated dz - sepsis like
```
Transmission prevention:
- suppress w/ acyclovir starting at 36 weeks
- c-section if active infection at time of labor
232
Congenital syphilis
25% --> death
Early manifestation - first 2 yrs of life:
hepatomegaly, elevated LFTs
Rash followed by desquamation of hands and feet
snuffles - blood tinged nasal secretions - copious
skeletal abnormalities
Late manifestations - after 2 yrs of life: scarring or deterioration
frontal bossing
interstitial keratitis - cornea scarring --> blindness
saddle nose deformity
hutchinson teeth - notching of upper incisors
perforation of hard palate
saber shin - anterior bowing of tibia
233
Tx of syphilis in pregnant patient who is allergic to penicillins
PCN G even if allergic to PCN still best tx
desensitization of PCN, gradually build up to full tx dose
234
Hepadnavirus
Hep B - dsDNA virus
partially ds circular DNA enter nucleus
Host polymerase makes RNA intermediate from dNA
viral reverse transcriptase makes DNA from RNA intermediate
235
Pneumoconiosis
Fibrotic lung dz w/ inhalation of inorganic dust particles
Coal dust, asbestos, silica
M0 release mediator – fibrosis of lung as try to clear
236
Coal worker’s pneumoconiosis (CWP)
Anthracosis – mild: black pigment in lung
-carbon particles trapped in M0 of connective tissue
Simple CWP – small fibrotic lung nodule
Complicated CWP – progressive massive fibrosis
Coal workers exposure risk: coal dust, silicon dioxide, radon –risk lung cancer
237
Silicosis
Inhaling silicon dioxide
Mining, sandblasting, construction, demolition, cement/concrete production, masonry/stone cutting, foundry work, hydraulic fracturing “fracking”
M0 take up silica -> inflammation
Innumerable calcified nodules
Egg shel calcifications in hilar nodes -> progressive massive fibrosis
Increased susceptibility of TB – M0 can’t kill them
Increased risk of lung CA x2 risk
238
Asbestosis
Shipbuilding, roofing, pipe fitting, plumbing
Spouse doing laundry
Fibers in peripheral lung – lung bases
Directly toxic to lung parenchyma
M0 release inflammatory mediators -> damage
Fibers covered w/ iron containing protein – ferruginous bodies
- “dumbbell” shape
- golden brown w/ Prussian blue stain
pleural plaques
pleural effusions
interstitial fibrosis
Increased cancer risk:
Laryngeal CA, malignant mesothelioma, lung cancer: squamous cell, adenocarcinoma
Bronchogenic carcinoma much more common than mesothelioma in asbestos exposure
Smoking and asbestos exposure increases lung CA risk 60 fold
239
Berylliosis
High tech electronics, aerospace manufacturing
Noncaseating granulomas similar to sarcoidosis
Increase risk of lung CA
240
Sarcoidosis
AA, young females 30-40s
“A GRUELING Disease”
ACE enzyme increase
Gammaglobulinemia
Rhematoid factor
Uveitis (and other ocular manifestations) vascular layer
Erythema nodosum – tibia, sq fat inflammation
Lymphadenopathy – b/l hilar
Idiopathic
Noncaseating
Granulomas
vitD increase – activated M0 in granulomas -> hypercalcemia/-uria
Tx: glucocorticoids
241
Granulomatosis w/ polyangiitis aka Wegners
Triad:
Necrotizing granulomas of lung and upper airway
Necrotizing granulomatous vasculitis most prominent in lungs and upper airway
Focal necrotizing granulonephritis
242
Central lung cancers
Squamous cell carcinoma of lung
| Small cell carcinoma of lung
243
Peripheral lung cancers
Adenocarcinoma
| Large cell carcinoma of lung
244
Lung cancer sx
Cough
hemoptysis
Chest pain
```
Wt loss
Night sweats
Pneumonia
Pleural effusion
Airway obstruction
Paraneoplastic sn
```
245
Adenocarcinoma of lung
36%- MC lung cancer
Peripheral lung – pre-existing parenchymal scars
Risk factors: smoking, gene mutations “MARKER”
MET, ALK, RET, KRAS, EGFR, ROS
MC nonsmokers and females
246
Squamous cell carcinoma of lung
20% 2nd MC lung cancer
Central lung – hilar mass in bronchus, cavitated lesion on CXR/CT
Risk factor: smoking
Histo: Keratin pearls
Can secrete PTH-related protein --> hypercalcemia
247
Large cell carcinoma of lung
Peripheral lung
Risk factor smoking
Histo: anaplastic and undifferentiated, giant cells with various pleomorphisms
Poor prognosis
248
Small cell carcinoma of lung
High nucleus:cytoplasm ratio
Risk: smoking
Central lung
Hormone secretion:
ACTH -> Cushing Sn
ADH -> SIADH
Ab against presynaptic Ca2+ channels -> Lambert-Eaton Sn (muscle weakness improves w/ use)
Undifferentiated, very aggressive
Poor prognosis
TP53, Rb gene mutations
Amplicfications of MYC
249
Carcinoid tumor
1—5% lung tumors
low-grade malignant tumor secretes serotonin
```
Carcinoid syndrome “BFDR”
Bronchospasm and wheezing
Flushing
Diarrhea
Right-sided heart lesions (valvular lesion, murmur)
```
Lung and GI tract – MC tumor of appendix
75-80% pts w/ carcinoid sn have small bowel carcinoid
Most do not met
Has to be outside of GI to have sx
250
Pancoast turmor
Apex of lung
Most non-small cell lung cancers
Horner sn (ptosis, miosis, anhidrosis)
May compress recurrent laryngeal n. -> hoarseness
251
Mesothelioma
In pleura
Risk factor: asbestos exposure – not MC cancer w/ exposure – bronchogenic carcinoma
Poor prognosis
No smoking associations
252
Lung cancer mets to other sites
Brain
Bone
Liver
Adrenal glands
253
Lungs receive mets from
Breast
Colon
Prostate
Bladder
254
Paraneoplastic sn assoc w/ lung cancers
Squamous cell carcinoma -> hypercalcemia
Small cell carcinoma -> SIADH, Cushing Sn, Lambert-Easton
255
Compression complications in lung cancers
Hoarseness – recurrent laryngeal n. compression
Horner’s sn – Pancoast
Dysphagia – esophageal invasion
SVC syndrome – impaired drainage of blood from head
256
Draw table for sensitivity, specificity, PPV, NPV
Pg 482
257
Sensitivity
Number with a positive test that have the dz
258
Specificity
Number w/o dz that tests negative
259
PPV
Likelihood positive test = dz
260
NPV
Likelihood – test is dz free
261
How does changes in prevalence impact PPV and NPV?
Increase in dz Increases A = increased PPV
Decrease in dz decreases A = decreased PPV
Increased dz increases C = decreased NPV
Decreased dz decreases C = increased NPV
262
Relative risk
Cohort study
Probability of getting dz in exposed group vs getting dz in unexposed group
A/A+B / C/C+D
If low dz = A/B / C/D
263
Odds ratio
Approximates relative risk if low prevalence
A/B / C/D
264
Attributable Risk (AR)
AR = incidence of dz (exposed group) – incidence of dz (unexposed group)
AR = A/A+B – C/C+D
265
Absolute risk reduction
No intervention – intervention
ARR = C/C+D – A/A+B
Control – experimental grp
266
Number needed to harm
1/AR
267
Number needed to treat
NNT = 1/ARR
Number of patients you need to treat to save/affect one life
Important number to help determine if a drug should be used or is cost effective
268
Precision (reliability)
How reproducible result is
Consistent test
No necessarily accurate
269
Accuracy (validity)
How closely results reflect the truth
270
Beneficence
Ethical duty to act in pt’s best interest
271
Autonomy
Pt right to chose what’s done to them
Physician: chose what tx will or will not provide
272
Nonmaleficence
Avoid intentionally harming pt
273
Justice
Treat people fairly
274
Privacy breaking situations
Child abuse
Dz reporting
Schools
Employers – record of illness
275
Informed consent
```
Understanding of:
Procedure/tx
Risk involved
Expected benefits
Alternatives
```
276
Decision making capacity
```
Must be able to make and communicate a decision
Informed
Decision must be:
Consistent w/ pt values and goals
Stable over time
Not based on delusions or hallucinations
```
277
Substituted judgement
Substitute someone else’s consent for pt’s consent
278
Advanced directives
Oral AD
| Written AD – living will
279
Durable power of attorney for healthcare
Make decision
280
No assignment of surrogate decision maker
Legally assigned order:
Spouse
Adult kids
Pt parents
Siblings
281
Treating minors
Informed consent from parents or legal guardian
```
Except: own conset:
16 yo, on own – emancipated
STDs
Pregnancy
Drug addiction
Child of minor
Serving sentence of confinement
Emergencies
```
282
Failure modes and effects analysis (FMEA)
Proactive, systemic analysis of how a process might fail and impact of these failures in order to identify parts of process most in need of change
1. List steps in process
2. Identify failure modes “what could go wrong”
3. Identify failure causes “why would the failure happen”
Identify failure effects “what are the consequences of each failure”
283
Strategies for Ethics questions
Always remain professional
Maintain good physician-patient relationship
Respect pts rights to privacy and autonomy
284
Pregnant teen adoption/abortion
Can’t be forced to abort or adopt by parents
Teen wanting abortion – state laws
Most require parent notification or consent if elective and not emergent
285
Financial relationships of physician
Unethical to get kickbacks for referring to specific facility for healthcare
Referrals to facility w/ ownership stake is unethical
286
Malpractice claim components
Duty to provide care
Breach of duty
Harm to patient
Damage suffered (emotional, physical, financial)
MC: lack pt/dr relationship
287
Autosomal Dominance heritance pattern
1 allele mutation cause dz
structural genes- usually
every generation effected
288
Common AD disorders
```
ADPKD
Achondroplasia
FAP
Familial hypercholesterolemia
Osler-Weber-Rendu Sx
Hereditary spherocytosis
Huntington dz
Marfan dz
MEN
NF type 1 and 2
Tuberous sclerosis
Von Hippel-Lindau dz
```
289
Autosomal recessive heritance pattern
25% receive 2 recessive alleles
only in 1 generation
-enzyme deficiency usually
-not all are recessive but often are
290
Common AR disorders
```
Albinism
ARPKD
CF
Mucopolysaccharidosis
PKU
Sickle cell dz
Sphingolipioses
Glycogen storage dz
Hemochromatosis
Thalassemias
Wilson dz
```
291
X linked recessive heritance pattern
Males 50% effected
| Females 50% carriers
292
X linked recessive disorders
“Oblivious Female Will Give Her Boys X-linked Disorders”
```
Ocular albinism
Fabry dz
Wiskott-Aldrick
G6PD deficiency
Hunter Sn
Bruton alpha-gammaglobinemia
```
Hemophila A and B
Lesch-Nyhan Sn
Duchenne muscular dystrophy
293
Review inheritance diagrams
Pages 524-525
294
Mitochondrial inheritance defects
Mitochondrial myopathies – ragged-red muscle fibers on bx
Leber hereditary optic neuropathy
Leigh syndrome – subacute sclerosing encephalopathy
Only female offspring affected
295
X linked dominant
Transmitted though both
All females of affected male will have it
Ex: fragile X syndrome
296
Anticipation
Age of onset earlier and earlier in successive generations
Or severity of dz worsens w/ successive generations
297
Codominance
2 alleles neither dominant (ABO)
298
Variable expression
Severity of phenotype varies from 1 to another
| Ex: tuberous sclerosis
299
Pleiotropy
Single gene has more than 1 effect on phenotype (PKU)
300
Locus heterogeneity
Mutaitons of different loci -> same phenotype
Marfan, MEN2B, homocysteinuria
-> same marfanoid body habitus
301
Mosaicism
Cells in body w/ different genetic makeup
302
Imprinting
Phenotype differences depend on if mutation from mom or dad genes
Prader Willi vs Angelman sn
303
Prader-Willi Sn
“Papa”
Deletion of Proximal Portion of Chr 15q11-q13 from Paternal origin
Infant: hypotonia, poor feeding, characteristic facial features (almond-shaped eyes, downward turned mouth)
Sx: hyperphagia, obesity, short stature (partial GH deficiency), intellectual disability, behavior disorders (tantrums, skin picking, OCD), hypogonadotropic hypogonadism -> genital hypoplasia, osteoporosis in childhood, delayed menarche
Dx: confirmed w FISH
Tx: limit access to food, GH if short stature
304
Angelman syndrome
Deletion of Chr 15
Paternal inactivated, maternal deleted
Intellectual diability, seizures, inappropriate laughter “happy puppet”
Ataxic gate
305
Prader willi vs Angelman
POP:
Prader willi
Obesity/Overeating
Paternal gene
```
MAMA:
Maternal gene
Angelman (Angel MOM)
Mood- happy, laughter
Ataxia
```
306
Hardy-weinberg population genetics
P+q =1
| P2 + 2pq + q2 = 1
307
Review gel electrophoresis and DNA sequences
Page 528
308
Draw out phenylalanine derivative pathway
Page 556
309
PKU
Deficient in phenylalanine hydroxylase OR cofactor tetrahydrobiopterin (BH4)
Tyrosine becomes essential aa
Avoid phenylalanine -> phenoketones: phenyl-acetate, -lactate, -pyruvate
```
Growth retardation
Intellectual disability
Seizures
Fair skin
Eczema
MUSTY body odor
```
Screen 2-3 days old
Tx: avoid phenylalanine: aspartame, diary products, meat, fish, chicken, eggs, beans, nuts
Add tyrosine into diet
+/- BH4
w/ in 3 wks of life
310
PKU mom –non managed effects on baby
Microcephaly
Intellectual disability
Growth retardation
Congenital heart defects
311
Vit D toxicity
Hypercalcemia
| -assoc w/ sarcoidosis: M0 in granulomas increase conversion to active form of Vit D
312
Draw vitamin D activation pathway
Page 561
313
Vitamin K
Post translational modification of various clotting factors
-synthesized by intestinal floral
diSCo 1972: Protein C, S, factors 10, 9, 7, 2
decrease w/ warfarin
314
Vit K deficiency
Warfarin
Anticonvulsants – phenytoin
Abx: wipe out gut flora
Newborns have problems with hemorrhage
- sterile gut, can’t make vit K
- give single vit K injection at birth
315
Vit D deficiency
Inadequate dietary Vit D – breast milk not adequate enough Vit D – supplement
Impaired hydroxylation to make 25-OH vit D in liver
Impaired kidney hydroxylation to make 1,25-(OH)2 Vit D
End organ insensitivity to Vit D
Sx: kickets – kids; osteomalacia adults
```
Bone tenderness
Muscle weakness
Skeletal deformity
Bowing of legs
Growth problems
Pathologic fx
Dental problems
```
316
Vit A
Retinol – eye and immune system, maintenance of epithelial cells and mucus secreting cells
Retinal
B-carotene – cleaved to 2 retinols
Retinoic acid – unusable tx
Use:
Decrease size and secretion of sebaceous glands:
mild to mod acne – tretinoin
Severe acne – oral isotretinoin
Measles
AML – M3 subtype
Pregnancy – risk teratogenicity w/ supplementation
317
Vit A deficiency
Night blindness
Xerophthalmia -> corneal ulceration and blindness
Keratomalacia – wrinkling and clouding of cornea
Bitot spots – silver/gray plaques on conjunctiva
318
Vit A toxicity
```
HA
N/V
Stupor
Increased ICP – pseudotumor cerebri
Dry and pruritic skin
Hepatomegaly
+/- cirrhosis
bone and joint pain
alopecia
```
319
Vit E – alpha-tocopherol
Antioxidants esp RBCs
```
Deficient:
Hemolytic anemia
Spinocerebellar degeneration -> ataxia
Peripheral neuropathy
Proximal m. weakness
```
320
Vit C ascorbic acid
Hydroxylation of prolyl and lysyl residues of collagen
Regulate dopamine -> NE by dopamine beta-hydroxylase
Antioxidant – protect RBCs
Facilitates iron absorption in gut
```
Deficiency – scurvy
Sore, spongy gums
Loose teeth
Fragile blood vessels
Swollen joints
Hemarthrosis
Impaired wound healing
Anemia
```
321
Diagnostic sx of major depressive disorder
5/9 sx:
DIGS CAPES
At least 1:
Depressed mood
Interest diminished – anhedonia
Guilt or worthlessness
Sleep disturbances – increased or decreased
Concentration impaired
Appetite or wt changes (up or down)
Psychomotor agitation or retardation
Energy loss – fatigue
Suicidal ideation – recurrent thoughts of death – preoccupation w/ death
322
Cluster A personality disorders
Paranoid
Schizoid
Schizotypal
“weird ones”
no psychosis
323
Paranoid personality disorder
Long standing suspiciousness and generalized distrust of others
Use projection
324
Schizoid personality disorder
Voluntary social withdrawal
| Limited emotional expressions
325
Schizotypal personality disorder
Eccentric appearance
Odd beliefs
Magical thinking
326
Cluster B personality disorders
All about drama, scary
Antisocial
Borderline
Histrionic
Narcissistic
327
Antisocial personality disorder
M>F
Disregard for and violation of others rights
-> criminality
lack empathy
328
Borderline personality disorder
Unusual variablility and depth of mood
Unstable mood
Chaotic interpersonal relationships
Manipulative and impulsive
Self mutilation – cutting
Splitting
Won’t remember negative behavior
High suicide rate **
329
Histionic personality disorder
Excessive emotions
Attention seeking
Seductive behavior
Overly concerned with appearance – exaggerated
330
Narcissistic personality disorder
Excessively preoccupied w/ personal prestige, power and vanity
Lack empathy
Require excessive admiration
React to criticism w/ rage
331
Cluster C personality disorders
Anxiety, fearful, cowardly, compulsive, clingy
Avoidant
Obscessive compulsive
Dependent
332
Avoidant personality disorder
Hypersensitivity to rejection
Socially inhibited and timid
Feelings of inadequacy
Desire relationships with others
333
Obsessive compulsive personality disorder
Preoccupied w/ order, perfectionism and control
334
Dependent personality disorder
Psychologically dependent on others
Low self esteem
Excessive need to be taken care of
335
Membranoproliferative nephritis
Hep B, C
Lupus
RA
Monoclonal gamopathies
336
Glomerulonephritis (GN)
```
Light proteinuria
Hematuria
RBC casts
Azotemia (elevated BUN/Cr)
HTN
Oligouria
```
337
Post-strep glomerulonephritis
Preceeded by Grp A strep – throat, impetigo
1-3 wks prior
Type III HSR – immune complexes deposit in glomeruli
Abx tx of strep does not prevent PSGN
-prevents acute rheumatic fever and heart disease
MC: kids
-borwn urine: “tea colored” “coca cola”
Renal bx: hypercellular glomeruli, N0
Dark “lumpy bumpy” subepithelial humps
-under foot process
Deposited in mesangium along BM:
- IgG and IgM complexes
- C3
activation of complement -> low C3
elevated ASO titer – may not elevate in impetigo
elevated anti-DNase B – in all infections
338
Alport Sn
Type IV collagen – BM
Splitting of BM
Eye problems – cataracts, lenticonus
Nephritis
Deafness – high frequency hearing loss
“Can’t see, can’t pee, can’t hear high C”
339
Rapidly progressive GN
-> RF fast
Cresentric GN: “crescendos”
- cresent shaped deposits in glomeruli
- fibrin, compliment, cell debris
Good pasture dz
Granulomatosis w/ polyangiitis
Microscopic polyangiitis
Lupus
340
Good pastures dz
Type II HSR
Ab against BM
Linear Ab pattern – “fence pasture”
Pulmonary hemorrhage/hemoptysis
341
Granulomatosis w/ polyangiitis
Lungs, kidney, upper airway – sinuses, hard palate
+cANCA – PR3-ANCA
342
Microscopic polyangiitis
pANCA, MPO-ANCA
343
IgA nephropathy – Berger dz
Assoc w/ Henoch-schonlein purpura
IgA immune complexes deposited in mesangium – dark, dense blobs in mesangium
Hematuria w/ RBC casts
Flares up after infection
344
Henoch-Schonlein purpura
```
Palpable purpura on buttocks and legs
Arthralgias
Abd pain
Intestinal hemorrhage
Renal dz – IgA nephropathy
```
345
Diffuse proliferative glomerulonephritis
MC – severe form of lupus nephritis
Anti-dsDNA/DNA complexes deposit in subepithelium – between epithelium and BM
Line BM
Wire loop “wire lupus”
Can present as nephritic or nephrotic
346
Nephrotic syndrome
```
Proteinuria > 3.5 g/d
Hypoalbuminemia
Edema
Increased risk infection
Increased risk thrombosis
Hyperlipidemia
```
347
Minimal change dz
Bx: flattening or effacement of podocyte foot processes
-> More permeability to protein
MC cause of nephrotic sn in kids
Triggered by infections/immunizations
Tx: corticosteroids
348
Focal Segmental Glomerulosclerosis (FSGS)
AA and Latinos
HIV pts*
Bx: focal and segmental sclerosis – regions affected
349
Membranous glomerulonephropathy
White adults
Bx:
Thickening of BM
Subepithelial immune deposits along BM
Domes and spikes**
350
Membranoproliferative GN
Nephritic and nephrosis
“tram track” appearance – mesangium invades between “tracks”
IgG immune complex along BM
-subendothelial humps
Hep B, C, lupus, subacute bacterial endocarditis*
351
Diabetic nephropathy
Microalbuminuria -> nephrotic sn
Thickening of GBM
Kimmelstiel – Wilson nodules
-round acellular nodules w/in glomeruli – pink
mesangium dramatically expanded
352
Amyloidosis
Massive expansion of mesangial matrix
Amyloid protein deposits in mesangium
Congo red stain – apple green birefringence assoc w/ multiple myeloma
353
APGAR
Appearance: cyanotic 0, acrocyanosis 1, pink 2
Pulse/HR absent 0, less than 100 1, over 100 2
Grimace no response to stimulation 0 cry, pull away 2
Activity/tone limp/floppy 0 flexed arms and legs, resists extension 2
Respiration no effort 0 slow irregular, labored 1 crying, vigorously breathin 2
354
3 mo milestones
Gross motor: roll over
Fine motor: hands together
Verbal/Cognitive: laughing and squealing
Social/self-care
355
6 mo milestones
Gross motor: sit up unassisted
Fine motor: transfer cube
Verbal/Cognitive: single syllables
Social/self-care self feed
Start of stranger anxiety
356
9 mo milestones
Gross motor: crawling
Fine motor:
Verbal/Cognitive: object permanence
Social/self-care
Stranger anxiety
357
12 mo milestones
Gross motor: stand, walk
Fine motor: block into cup
Verbal/Cognitive: 1-3 words
Social/self-care drink from cup
Stranger anxiety transitioning to separation anxiety
358
15 mo milestones
Gross motor: walk backward, run
Fine motor: 2 cube tower
Verbal/Cognitive: 6 words
Social/self-care use utensils – fork, spoon
Separation anxiety
359
18 mo milestones
Gross motor: climb stairs, kick a ball
Fine motor: 4 cube tower
Verbal/Cognitive: combine words
Social/self-care brush teeth w/ help
360
2 y milestones
Gross motor: jump up
Fine motor: 6 cube tower
Verbal/Cognitive: half understandable
Social/self-care wash/dry hands
361
3 y milestones
Gross motor: jump forward, ride tricycle
Fine motor: copy circle
Verbal/Cognitive: understandable
Social/self-care pour cereal, brush teeth, dress, play board games, potty training
362
4 y milestones
Gross motor: hop on 1 foot
Fine motor: copy a plus sign
Verbal/Cognitive:
Social/self-care button clothes, magical thinking
363
5 yo milestones
Gross motor: tie shoes
Fine motor: copy square and triangle
Verbal/Cognitive: identify colors, coins, count to five
Social/self-care
364
6 yo milestone
Gross motor:
Fine motor:
Verbal/Cognitive:
Social/self-care – logical thinking “if…then…”
6-11 other sex is “yucky”
365
Draw out steroid synthesis pathway
Page 639
366
S/S of Cushing syndrome
“BAM CUSHINGOID”
Buffalo hump
Amenorrhea
Moon facies
```
Crazy
Ulcers
Skin changes – easy bruising, acne, purple striae, thin skin
HTN
Infection
Necrosis of femoral head
Glaucoma
Osteoporosis
Immunosuppression
Diabetes
```
367
Embryonic origin and development of thyroid
Begins week 3
| Derived from endoderm from floor of primitive pharynx
368
Diabetes mellitus
Hyperglycemia -> polyuria, polydipsia, polyphagia, wt loss
Diagnostic tests:
Fasting serum glucose
2hr OGTT
Hemoglobin A1c
369
Type 1 DM
Islet cells Ab against glutamic acid decarboxylase (GAD)
Primary insulin deficiency – younger onset
Assoc w/ HLA on CHr 6:
HLA-DR3 – DQ2
HLA-DR4 – DQ8
Acute complications: DKA
370
Type 2 DM
Insulin resistance -> inadequate insulin production – burns out
Middle age or older
7/8 overweight or obese
very hereditary
other metabolic problems – high TG, cholesterol
HTN
Acanthosis nigricans on flexural areas
371
Nonenzymatic glycation in DM
Glucose tacked onto:
Hemoglobin
Small blood vessels -> leaky
372
Retinopathy of DM
Glycation of small vessels of retina
Nonproliferative
w/ new vessel formation -> proliferative
-fragil new vessels hemorrhage -> blindness
macular edema
cotton wool spots – not specific to DM
Need annual dilated eyes exam
373
Diabetic nephropathy
Proteinuria
Progressive
Decreased by ACEI/ARBs
Kemmel Still-Wilson nodules – acellular nodules in glomerulus
374
Diabetic vascular disease
Contributes to atherosclerosis -> coronary artery disease, stroke, PVD
-> dry gangrene -> amputations
375
Diabetic neuropathy
Glucose –aldose reductase --> sorbitol –sorbitol dehydrogenase --> fructose
Insufficient sorbitol dehydrogenase in tissues, sorbitol levels elevated
- schwann cells -> neuropathy
- lens
- retina
- Kidney
Sorbitol pulls water into cell -> swelling and damage
376
Motor, sensory, autonomic neuropathy in DM
Begins tips of toes, progresses proximally
Monofilament testing – can be asx early on
DM foot check – wounds, sensation
377
DKA physiology
Profound insulin deficiency:
Cells can’t get any glucose -> production of ketones
Body stimulated to make glucagon – cells starving
-> elevation of blood glucose -> excessive polyuria and dehydration
-> breakdown fatty acids into ketones -> profound acidosis
378
Precipitating factors for DKA
Absolute insulin deficiency:
Undx DM
Missed insulin dose
Stress body -> increased glucagon, catecholamines, cortisol:
Infection – pneumonia, gastroenteritis, UTI
Severe ischemic events – MI, CVA
Trauma
Dehydration
Alcohol and drug abuse (cocaine)
379
Clinical features of DKA
Sx preceding acute illness
- polyuria, polydipsia, wt loss
- > dehydration
abd pain, N/V
confusion, delirium
sweet, fruity odor to breath
Kussmaul breathing – deep labored breathing, blowing off CO2
380
DKA labs
Anion gap metabolic acidosis
Hyperglycemia of at least 250
Serum and urine ketones
Hyperkalemia – H/K ATPas exchanger pulls H+ into cell -> K+ out
-kidneys dump K+ -> total body K+ very low
381
DKA complications
Arrhythmias – VT, torsades (low Mg)
Invasive fungal infecitons
-mucormuycosis, rhizopas -> invade sinuses -> brain abscess
382
Tx of DKA
ICU
IV vluids
Insulin drip – stops ketone production, promotes glucose use
Monitor anion gap
- insulin until gap closed, switch to IM
- may need to coadminister w/ glucose
Potassium
May need Mg2+
383
Hyperosmolar hyperglycemic state (HHS)
Primary presenting sx:
Confusion, delirium, coma
-> dehydration, N/V, abd pain
tx: IV fluids, insulin, potassium
monitor serum osmolarity
384
DKA vs HHS
DKA:
Ketoacidosis – insulin absent
Hyperglycemia over 250
Anion gap
```
HHS:
No ketoacidosis – insulin present
Extreme hyperglycemia >800
Serum hyperosmolarity > 340
No anion gap
```
385
Biguanides
Metformin
Decrease hepatic gluconeogenesis
Improves insulin sensitivyt
Does not cause wt gain
SE:
GI side effects common
Increased risk of lactic acidosis in renal failure
Caution w/ IV contrast – stop to prevent problems for a couple days
386
Sulfonylureas
Glimepiride
Glipizide
Glyburide – more hypoglycemia
Stimulates continuous insulin release from beta cells
Close K channel in beta cell -> depolarizes, increased Ca2+ influx
SE:
Hypoglycemia – long lasting
Wt gain
Require pancreatic function
387
Thiazolidinediones (TZDs)
“-glitazone”
Pioglitazone
Rosiglitazone
Improves insulin sensitivity
Decreases hepatic gluconeogenesis
Binds PPAR gamma receptor – adipose, sk.m., liver
SE:
Wt gain
Increased fluid retention -> increased risk of CHF
Possible hepatotoxicity
388
DPP-4 inhibitors
```
-gliptin
Sitagliptin
Alogliptin
Saxagliptin
Linagliptin
```
Inhibits DPP-4 which increases endogeneous GLP1 (inhibit the inhibitor)
- > stimulation of insulin release, inhibit glucagon release -> lower blood glucose
- ->delays gastric emptying
wt neutral
Low risk of side effects
389
GLP1 agonists
```
-glutide
Exenatide
Liraglutide
Albiglutide
Dulaglutide
```
Mimic incretin hormone GLP1
- decreases glucagon
- increases insulin secretion
- delays gastric emptying (which reduces appetite)
effect glucose dependent
Wt loss
SE: nausea
390
SGLT2 inhibitors
-flozin
Dapagliflozin
Empagliflozin
Canagliflozin
Inhibit Na+/glucose linked transporter in kidney -> glucose loss in urine
```
SE:
Risk w/ kidney dysfunction
UTIs, mycotic infections
Dehydration, polyuria
Possible DKA
```
391
Metabolic syndrome diagnostic criteria
Any 3:
Abdominal obesity: over 40 in in men, over 35 in women
TGs over 150
HDL less than 40 in men, less than 50 in women
BP: over 130/85
Fasting serum glucose over 100 or 2 hr post OGTT over 140
392
Warfarin
Inhibits epoxide reductase which recycles vit K
Increases PT
Used for chronic anticoagulation for afib, DVT prophylaxis and treatment, PE tx – prevents extension
Contra: pregnancy: bone/cartilage problems in epiphyses, nasal hypoplasia
-use heparin or LMWHs
393
Platelet disorders
Microhemorrhages
- bleeding from mucous membranes
- epitaxi
- petechiae – flat brown/red dots
- purpura
increased bleeding time
normal PT/INR, PTT
394
Immune thrombocytopenia (ITP)
```
Chronic
Auto Ab (antiplatelet Ab) to GpIIb/IIIa on surface of platelets
-immune system destroys platelets
-> low platelets
high megakaryocytes on BM bx
```
Tx: steroids, IVIG, splenectomy – more platelets in circulation
395
ADAMTS13
A disintegrin and metalloprotease w/ thrombospondin type I motif, number 13
Contains Zn
vWF multimers released from injured endothelial cells, ADAMTS13 cleaves multimers into smaller, active vWF units
396
Thrombotic thrombocytopenic purpura
Excessive platelet activation -> widespread platelet thrombosis -> thrombocytopenia -> bleeding and purpura
Deficency of ADAMTS13 -> vWF multimers not broken down
Unregulated platelet aggregation -> widespread thrombosis
Consumption of platelets -> thrombocytopenia
Activation of coagulation cascade -> excessive fibrin mesh -> microangiopathic hemolytic anemia, schistocytes, elevated LDH
397
Hemolytic uremic Sn (HUS)
Milder form of TTP
| Kids – assoc w/ Ecoli O157:H7 infection
398
Glanzmann Thrombasthenia
Genetic – chronic
Defect in glycoprotein IIb/IIIa -> abnormal platelet aggregation -> no plug
Normal platelet count
Increased bleeding time
399
HUS vs TTP
HUS:
Hemolysis
Renal insuffiency (uremia)
Thrombocytopenia
TTP: HUS + fever and neurological sx (HA, confusion, seizures, coma, focal deficits like a stroke)
```
TTP: “FAT RN”
Fever
Anemia
Thrombocytopenia
Renal failure
Neurological sx
```
400
Bernard-Soulier Sn
Genetic – chronic
Defect of GpIb -> platelet can’t bind to collagen -> defect of platelet plug formation
Platelet enlarged, removed form circulation -> moderate thrombocytopenia
Increased bleeding time (primary dysfunction)
401
Von Willebrand Dz
Mixed platelet and coagulation disorder
MC inherited bleeding disorder
-defect of vWF
```
increased PTT (not stabilizing factor VIII)
Increased bleeding (platelets can’t adhere)
```
Dx:
vWF level
Factor VIII activity
Ristocetin cofactor assay –agglutinate RBC w/ vWF present: + if no agglutination
402
Disseminated intravascular coagulation (DIC)
Acute, lifethreatening
Widespread activation of clotting ->
- consumption of platelets and coagulation factors
- hypocoagulable state -> bleeding
low platelets, elevated bleeding time
high PT/PTT
low fibrinogen, high fibrin split products (D-dimer)
Schistocytes on peripheral smear
Bleeding
Multiorgan failure
```
Causes: “STOP Making Thrombi”
Sepsis (gram -)
Trauma
Obstetrics complications (amniotic fluid emboli, placental abruption)
Pancreatitis (acute)
Malignancy
Transfusion
```
403
Small cell lung CA paraneoplastic effects
ACTH -> Cushing Sn
ADH -> SIADH ( low serum osmolality, hyponatremia -> seizures)
Lambert Eaton Sn
- muscular weakness d/t Ab against presynaptic Ca2+ channels at NMJ
- Test – isometric m. contraction – when let go able to contract m. strong d/t buildup of Ca2+
- weakness improves w/ use
Cerebellar degeneration
-AutoAb attack purkinje cells in cerebellum -> dizziness and ataxia
404
Squamous cell lung cancer paraneoplastic effects
Humoral hypercalcemia of malignancy
Tumor secretes PTHrP (like PTH)
- > increased bone turnover, increased Ca2+ reabsorption in kidney
- > elevated serum Ca2+
405
Multiple myeloma paraneoplastic effects
Secretes local osteolytic factors -> lytic bone lesions -> hypercalcemia
406
HL paraneoplastic effects
Secrete active vit D -> hypercalcemia
407
PSA
Prostate CA
| Any pathology increases PSA – BPH, prostatitis
408
CA125
Ovarian CA
| Anything irritation the peritoneum elevates CA125
409
Alkaline phosphatase
Bone mets
Biliary dz
Paget dz of bone
410
Alpha-fetoprotein
Hepatocellular carcinoma
| Testicular tumor
411
CA19-9
Pancreatic cancer
412
CEA
Colon and pancreatic cancer
413
S100
Melanoma
Schwannoma
-neural crest origin
414
Tartrate resistant acid phosphatase (TRAP)
Hairy cell leukemia
