Clinical Applications Week 1 Flashcards
(67 cards)
1
Q
Listeriosis
A
serious food poisoning
listeria monocytogenes
mechanism:
ActA → hijacks Arp2 /3 → actin rapidly propels bacteria → protrudes to adjacent cell to infect
Symptoms:
- fever
- muscle aches
- nausea
- diarrhea
2
Q
Alzheimer Disease
A
Tau: MAP, multiple microtubule binding domains to form bundles
TAU → phosphorylated and dissociates from microtubule in neuron → aggregates to form neurofibrillary tangles → neuronal degeneration
TAU → phosphorylated and dissociates from microtubules → promotes microtubule disassembly
3
Q
Retrograde transport of toxins
A
use DYNEIN to transport toxins to neuronal body
- clostridium tetani
- herpes simplex
- poliovirus
- rabies virus
4
Q
Asthenozoospermia
A
causes infertility
bent sperm flagella → poor motility
9 + 2 arrangement is disrupted in microtubules
- mutations in inner and outer dynein protein
5
Q
Primary Ciliary Dyskinesia
A
Symptoms:
- chronic respiratory tract infections
- infertility/ectopic pregnancy
- hearing loss
- abnormally positioned organs (Kartagener syndrome- mirror image reversal of organs)
6
Q
Kartagener Syndrome
A
mirror image reversal of organs
caused by primary ciliary dyskinesia
7
Q
Epidermolysis Bullosa Simplex
A
- mutations in keratin
- cell-to-cell contacts are weakened
epithelial tissue → blistering and trauma from mechanical forces
8
Q
Hutchinson Gilford Progeria Syndrome
A
mutation in LMNA
causes premature aging in infants
9
Q
Emery-Dreifuss Muscular Dystrophy
A
mutation in lamin binding protein or LMNA
Symptoms:
- normal intelligence
- atrophy of muscles
- stiff joints
- absent tendon reflexes
- toe walking (shortened achilles)
- abnormal cardiac rhythms
10
Q
Dunnigan Lidodystrophy
A
mutation in lamin binding protein or LMNA
- variable loss of fat from extremities/trunk
- excess subq fat in chin/supraclavicular region
- begins at puberty
11
Q
Multiple Sclerosis
A
chronic autoimmune demyelinating of the CNS
- peak age 20-40
- Myelin sheath prevents current leakage and improves signal propagation; important to maintain speed
Symptoms:
- sensory loss/paresthesia
- optic neuritis (inflammation of optic nerve causing eye pain/blurred vision)
- weakness, diploplia, ataxia
- Lhermitte sign (electrical sensation down spine when neck is flexed)
- Bladder disfunction
- Cognitive disfunction
12
Q
Guillain-Barre Syndrome
A
Autoimmune disorder
- Molecular mimicry related demyelination in PNS
Symptoms:
- Proximal muscle weakness (rising from chair, combing hair, stairs)
- Rapidly evolving ascending paralysis
- Afebrile (not feverish)
- Antecedent infection (enteritis or upper respiratory/viral infection)
- Absence of reflexes
13
Q
illness script
A
epidemiology- age/risk factors
pathophysiology- why
key clinical features- time course, signs, symptoms
diagnostic data
treatment
14
Q
homocystinuria cause
A
cystathionine beta-synthase deficiency
- autosomal recessive
- can also be acquired- diet lacking B12, B6, foliate
15
Q
homocystinuria epidemiology
A
both males and females, but occurs more often in males
identified on state newborn screening labs
1/100,000-300,000
16
Q
Homocystinuria progression
A
- unaffected at birth with disease progression if untreated
17
Q
homocystinuria key clinical features- musculoskeletal
A
- marfanoid body habitus
- not necessarily tall
- hypotonia
- baby not meeting milestones
- osteoporosis
- especially increased risk after menopause
- pectus carinatum/excavatum
18
Q
homocystinuria key clinical features- CNS
A
- developmental delay
- intellectual disability
- psychiatric/behavioral disorders
- seizures
19
Q
homocystinuria key clinical features- opthalmologic
A
- INFERIOR lens dislocation
- myopia
20
Q
homocystinuria key clinical features- cardiovascular
A
- thromboembolic disease
- prone to DVT and PE
- extensive atheromas at young age
- cerebrovascular disease
- myocardial infarction
21
Q
homocystinuria key clinical features- dermatologic
A
- fair complexion with sparse blonde hair
- hyperpigmentation/vitiligo if POC
- livedo reticularis- lacy skin pattern, not raised
22
Q
Homocystinuria basic science
A
autosomal recessive
cystathionine beta synthase mutation → cystathionine beta synthase enzyme deficiency → increased levels of homocysteine
- homocysteine binds to endothelial cells
- proinflammatory cytokines
- inflammation
- ischemia
- blood cloths
- homocysteine replaces cysteine
- in eye- zonular fibrosis → downward dislocation
23
Q
Homocystinuria diagnosis
A
increased levels of homocysteine in urine and serum
increased levels of methionine in serum
24
Q
homocystinuria differential dx
A
marfan syndrome
25
homocystinuria treatment
* low protein (methionine) diet
* B6, B12, foliate, betaine supplementation
* IV cysteine supplementation to infants
* genetic counselling
* multidisciplinary team approach
26
Marfan's Syndrome Epidemiology
both males and females
phenotype becomes more apparent with age
2-3/10,000
27
Marfan's syndrome key clinical features- cutaneous
thin, highly distensible skin
linear striae
28
Marfan's syndrome key clinical features- ocular
myopia
**UPWARD AND MEDIAL** lens dislocation
29
Marfan's syndrome key clinical features- cardiovascular
* Mitral valve prolapse
* may hear a click between systole and diastole
* aortic root dilation
30
Marfan's syndrome key clinical features- musculoskeletal
* long, narrow extremities
* tall stature
* longer wingspan than height
* chest wall asymmetries
* acachnodactyly (long, slender fingers)
* thumb sign
* wrist sign
* joint hyper-extensibility
31
Marfan's syndrome key clinical features- respiratory
blebs, bullae- predisposed to spontaneous pneumothroax
32
Marfan's syndrome basic science
autosomal dominant
FBN1 mutation resulting in ***_DEFECTIVE FIBRILIN-1_***
fibrillin loss → increased TBFbeta → decreased vascular muscle, extracellular matrix → compromised strength, elasticity
33
Marfan's Syndrome diagnosis
Skeletal abnormalities
personal/family history of aortic aneurism
Differential dx: homocystinuria, ehlers-danlos
34
Marfan's syndrome diagnostic tests
echocardiogram, x-ray, MRI
35
Marfan's syndrome treatment
genetic testing
multidisciplinary team approach
monitor aorta/valvular abnormalities
counsel to limit participation in contact sports/competitive athletics/heavy lifting
36
Ehlers-Danlos Syndrome epidemiology
both males and females
broad range of presentations
1/5-20,000
37
Ehlers-Danlos key clinical features
6 subtypes
* type 3
* hyper-mobility
* joint instability
* classical (type 1 and 2)
* joint instability and hyper-extensible skin
* vascular (type 4)
* easy bruising
* muscles and organs prone to rupture
* mitral valve prolapse
* flat feet, kyphosis, scoliosis
* tendon sprains, joint dislocations/subluxations
* impaired would healing
38
EDS Basic Science
* inheritance: varies by subtype
* Classical (types 1 and 2)
* autosomal dominant (50% de novo)
* COL5A1/COL5A2 mutation → ***_type V collagen_*** mutation
* type V collagen interacts with type I collagen
39
EDS diagosis
clinical exam
beighton score
genetic counseling (not available for type 3)
differential dx:
* marfan's syndrome
* OI
* Larsen syndrome
* include craniofacial abnormalities
40
EDS treatment
treat/manage pain with NSAIDs
physical therapy
orthotics/casting
education/counseling
41
Osteogenesis imperfecta epidemiology
both males and females
symptoms apparent from childhood
range from fatal neonatally to mild
1/ 20,000
42
OI key clinical features
* multiple fractures +/- bone deformities
* short stature
* blue sclera
* dental imperfections
* hearing loss
Type I
* mild bone fragility
* minimal fractures before walking
* normal stature
* higher risk of hearing loss/osteoporosis as adults
Type III-IX
* Type III is most severe that is compatible with life
* moderate to severe rate of fracture
* short stature
* hearing loss/osteoporosis later in life
Type II
* LETHAL
* fractures in utero
43
OI basic science
autosomal dominant
COL1A1/COL1A2 mutation
→ triple helix defect → decreased synthesis of ***_Type I collagen_***
44
OI diagnosis
* clinical signs
* family history
* x-ray skeletal survey
* dermal fibroblast culture
* may be less of normal collagen or abundant abnormal collagen
* differential dx
* CHILD ABUSE
* ricketts
* osteomalacia
45
OI treatment
Biphosphate treatment
surgical repair
physical therapy
46
Alpha-1 Antitrypsin deficiency epidemiology
both males and females
child with cholestasis and poor growth
young adult with emphysema +/- cirrhosis
47
AAT clinical features
* infant/child with cholestasis/poo growth
* younger adult patient with emphysema in a non-smoker
* more pronounced at base of lungs
* earlier/more severe if a smoker
* adult with cirrhosis
* portal hypertension/esophageal varices
* jaundice
* hepatocellular carcinoma
* decreased synthesis of coagulation factors
* panniculitis
* inflammation of subq fat
48
AAT basic science
autosomal dominant
SERPINA1 mutation → decreased or absent AAT → increased activity of proteases → increased breakdown of elastic → decreased elasticity of alveoli → COPD
misfolded ZAAT in liver → polymerization of ZAAT → iclusion bodies in hepatocyte ER → cirrhosis
49
AAT diagnosis
serum AAT level
gene sequency
liver biopsy
differential dx
* COPD
* cystic fibrosis
* interstitial pneumonia
50
AAT treatment
Monitoring:
* pulmonary functioning testing
* routine liver functioning testing
* liver ultrasound
therapy:
* avoid active/passive smoke exposure
* follow COPD guidelines for therapy
* pulmonary rehab
* nutritional support
* IV A1AT
* May require liver/lung transplant
51
Saxitonin poisoning
* Saxitonin: produced by algae and found in shellfish
* voltage-gated sodium channel blocker
* blocks action potentials in neurons/muscle cells
Symptoms:
* inactivation of sympathetic nerves: hypotension
* paralysis of diaphragm → death
* dyspnea
* headache
* nausea/vomiting/diarrhea
* generalized weakness
* hyporeflexia
* tingling/numbness
* around mouth/neck/face
52
Tetrodotoxin Poisoning
* Voltage gated sodium channel blocker
* affects nerve, skeletal, cardiac muscle
* comes from newts, shellfish, PUFFERFISH
* mild intoxication: euphoria, paresthesia around lips
Symptoms:
* nausea
* vomiting
* diffuse extremity weakness
* loss of reflexes
* bilateral ptosis
* bifacial weakness
* death from respiratory failure/cardiac arrhythmia
53
Hypokalemic Periodic Paralysis
* painless total body muscle weakness
* usually due to potassium shift intracellularly
* autosomal dominant
* mutation in L-type VGCC in muscle
* leads to activation of Na+-K+-ATPase
* potassium pumped into cell → less in serum
* membrane ***_HYPERPOLARIZES_*** (becomes more negative)
* muscle cells become less reactive to stimuli
* Clinical presentation:
* onset: adolescence
* transient generalized weakness sin arms/legs after exercise or carbohydrate intake
* treatment: PO potassium
54
Symptomatic hyperkalemia
older age due to chronic kidney disease, DM, CFD, medications
55
Hyperkalemic Periodic Paralysis
* Mutation in SCN4A (voltage gated sodium channel at neuromuscular junction)
* resting membrane potential gets ***_MORE POSITIVE_*** (depolarizes)
* when it gets above threshold potential, a muscle that has depolarized and contracted won't be able to repolarize to allow another contraction
* Clinical presentation:
* muscle weakness
* flaccid paralysis
* dyspnea
* nausea/vomiting
* paresthesia
* ***_peaked T-waves on ECG_***
* cardiac arrest
* Treatment:
* IV calcium gluconate
* calcium raises threshold and reduces firing
* albuterol
* insulin
* albuterol and insulin activate Na-K-ATPase and put potassium back into cells
* Glucose/Carbohydrate PO
56
dermatophagoides pteronyssinus
common dust mite
* inhaled fecal pellets contain serine and cysteine peptidases
* cleave occludins and ZO-1
* compromise TIGHT JUNCTIONS of respiratory epithelium
* Clinical presentation:
* wheezing
* SOB/chest tightness
* non productive cough
57
Clostridium perfringens
pathological agent found in meats
disrupts TIGHT JUNCTIONS
* enterotoxin binds claudins to prevent incorporation into tight junction in the epithelia of the intestines
* causes diarrhea
58
hypomagnesemia renal disease
progressive renal disease with characteristic magnesium wasting, progressive renal failure, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities
mutation in CLDN19
59
Ovarian cancer
beta catenin: transcription factor to activate genes promoting cell growth and proliferation
* migrates to the nucleus → mutations can promote its role as a transcription factor
* clinical presentation:
* bloating
* constipation
* increased urination
* early satiety
* family history
* often misdiagnosed as IBS
60
pemphigus vulgaris/foliaceus
autoimmune disease affecting DESMOSOMES
intraepidermal blistering due to acanthyolysis (adjacent epithelial cells pull apart)
* pemphigus vulgaris
* antibodies against desmoglein 3
* MUCOUS MEMBRANES AND EPIDERMIS
* pemphigus foliaceus
* antibodies against desmoglein 1
* expressed in desmosomes of SCALP AND FACE
61
bullous pemphigoid
subepidermal blistering
antibodies agaisnt: dystonin or type XVII colalgen
* blisters usually do not rupture
* unblistered skin peels and wrinkles when pressure is applied
62
dystrophic epidermolysis bullosa
mutation in type VII collagen
basement membrane separates from underlying tissue
* lifting off as a sheet is less severe than cells themselves separating
63
Cholera toxin
vibrio cholera
Mechanism: inhibits GalphaS GTP-ase activity (causing it to stay on, because hydrolysis of GTP turns off) → increased levels of cAMP
GalphaS stimulates Cl- and water secretion
Symptoms: severe diarrhea
64
Pertussis toxin
mechanism: inactivates GalphaI such that it cannot inhibit adenylyl cyclase → activity of cAMP increases
→whooping cough
65
Transfusion-Related Acute Lung Injury (TRALI)
characterized by sudden, acute respiratory distress during or within six hours or a blood component/product being administered
* dyspnea and tachypnea, SpO2\<90%
* bilateral pulmonary edema unassociated with heart failure
* recipient neutrophils are activated by donor-derived antibodies targeting human leukocyte antigens or human neutrophil antigens
66
Organophosphate poisoning
caused by acetylcholinesterase inhibition
acetylcholine increases at cholinergic neuroeffector junction
causes: drugs, insecticides
Symptoms: SLUDGEM
* salivation
* lacrimation
* urination
* defecation
* gastrointestinal upset
* emesis (vomiting)
* miosis (unable to focus/fixed close vision; ciliary muscles contracted)
* bradycardia/wheezing (smooth muscle contracted in lungs)
67
Fentanyl toxicity
pinpoint pupils
Respiratory distress
