NTR Flashcards
Waiter’s Tip
Erb Palsy- Upper Trunk c5/c6 injury
Total Claw Hand
Klumpke Palse [Lower trunk injury c8//t1]
Winged Scapula
Lesion of long thoracic nerve [c5,c6,c7]- serratus anterior
Flattened Deltoid, loss of arm abduction pass 15 degrees and loss of sensation over deltoid muscle plus loss of sensation over lateral arm
Axillary nerve injury - Surgical neck fracture
Wrist drop
Fracture of midshaft of humerus/ Radial nerve lesion
Ape hand or Pope’s Blessing
Supracondylar fracture of humerus/ Median nerve lesion
Ulnar Claw on EXTENSION
Ulnar never lesion [c8-t1]
Ape hand/ “Can’t abduct thumb”
Recurrent branch of median nerve [c5-t1]/ superficial laceration of palm
Femoral Neck Fracture, Distal Radial [Colles fracture], increased bone resorption
Due to low estrogen/ TYPE 1 postmenopausal Osteoporosis
Rx: Bisphosphonates, PTH, SERMs, Denosumab [RANK L monoclonal antibody]
Type 2 Oteoporosis
Normal Calcium, Phosphate, ALP and PTH in serum but trabecular/brittle bones
Osteoporosis
Normal Calcium [or maybe a little low if severe], Phosphate, ALP and PTH in serum but thick/easily fractured bones
OsteopeTROsis
Normal Calcium, Phosphate and PTH… but high ALP
Paget Disease
Low Calcium, Low Phosphate
High PTH and High ALP
Osteomalacia/Rickets
“brown tumors” due to fibrous replacement of bone, subperiosteal thinning
Osteitis fibrosa cystica
Always high PTH, always high ALP
If Primary hyperPTH, then high calcium and low phosphate
If Secondary hyper PTH then low Calcium and high phosphate
Soap bubble knee on x-ray w/ multinucleated giant cells
GIant cell benign tumor of epiphyseal plate
Mature bone mass with cartilaginous cap
Osteochondroma
Bone mass in metaphysis of long bones
Osteosarcoma [malignant]
t[11, 22] bone mass in diaphysis of long bones, pelvis, scapula and ribs + onion skin appearance in bone/ anaplastic small BLUE CELL malignant
Ewing Sarcoma
Glistening mass within the medullary cavity of the bone
Chondrosarcoma
Pain in weight bearing areas at the end of the day
+improves with rest
Osteoarthritis
- mechanical destruction of articular cartilage
- In Joint: Eburnation [polished ivory like appearance of bone], DIP and PIP only [no MCP]
Morning stiffness that improves with use + systemic sx: fever, fatigue, pleuritis and pericarditis]
Rhuematoid arthritis
- autoimmune destruction of synovial joints [cytokine mediated] 3 and 4 HSN
- In Joint: PANNUS formation - NO DIP involvement
ULNAR deviation of fingers
Decreased tear production + corneal damage, Decreased saliva production, Bilateral Parotid Gland enlargment
+ arthritis
Sjorgren syndrome
-autoimmune destruction of exocrine glands
Other issues: dental caries [no saliva], MALT lymphoma [if unilateral parotid gland enlargement]
How to alcohol make Gout worse?
Alcohol metabolities compete for same excretion sites in kidney as uric acid; causing lowered uric acid secretion and subsequent buildup in blood
Calcium pyrophosphate crystals w/in a joint
Pseudogout
Weakly positively birefringement [blue when parallel to light=— Gout was yellow]
Synovitis, Tenosynovitis and Dermatitis in sexually promiscuous person
Gonococcal arthritis [STD that presents as migratory arthritis with an ASYMMETRIC PATTERN] `
IgM that is an anti IgG antibody
+ anti cycle citrullinated peptide antibody [most specific to this Dx]
Rheumatoid Arthritis
B27- GROWN A “P.A.I.R.” !
P= Psoriatic arthritic [Dactilitis/ Sausage fingers- “pencil in cup” deformity on x-ray]
A= Ankylosing spondylitis ]- stiff spine due to fusion of joints + uveitis and AORTIC REGURGITATION “Bamboo spine]
I= Inflmmatory bowl dz: Crohns and UC can be linked to Ankylosing spondylitis or peripheral arthritis
R= Reiter’s Syndrome= Can’t see, can’t pee, can’t climb no tree! <– post GI infection from Shigella, Salmonella, Yersinia or Camplobacter or post CHYLYMIDIA infection
Wart like vegetations on BOTH SIDES of valve
Libman-Sacks Endocarditis linked to LUPUS!!!! [the vegetations do a LOOP around the valves/ attack both sides]
Widespread, noncasesating granulomas, elevated serum ACE levels
+ bilateral hilar adenopathy
+ Schaumann and Asteroid Bodies
+Uveitis
+HYPERcalcemia [due to increases alpha hydroxylase in kidney mediated by vita D activation in the macrophages]
Sarcoidosis
Increased ESR, Increase C-reactive protein, but normal CK [No muscle weakness!]
Polymyalgia Rheumatica linked to temporal giant cell arteririts
Widespread musculoskeletal pain in a younger woman [under 50] that’s linked to stiffness, paresthesias, poor sleep and fatigue
Fibromyalgia
“Shawl and Face” rash + Gottron papules [nodules in finger joints]
Labs: Increased CK, ANA, anti-Go, anti-SRP and anti-Mi-2
Dermatomyositis [perimysial inflammation and atrophy with CD4+ T cells] <– vs. Polymyositis [no cutaneous involvement only progressive muscle weakness characterized by endomysial inflammation with CD 8+ T cells]
AutoAbs to postsynaptic Ach receptor
“ptosis, diplopia, weakness that WORSENS with use”
*specific eye involvement!
Myasthenia Gravis
associated with THYMOMA/ Thymic hyperplasia
Reversal of symptoms with AChEsterase Inibitor administration
Myastenia Gravis
AutoAns to PRESYNPATIC Calcium chanell leading to decreased Ach release
+Muscle weakness and AUTONOMIC symptoms [like dry mouth and impotence] that IMPROVES WITH USE
links to SMALL CELL lung cancer [can ectopically release the autoantibodies to the presnaptic calcium channel]
- Lambert Eaton Syndrome [minimal to NO effect with AchEinhibitor administration]
Anti-Scl 70/ Anti DNA topoisomerase I antibody
Systemic Scleorderma: puffy and taut skin with ABSENCE OF WRINKLES [sclerosis of PULMONARY system= COD]
Anti centromere antibody
Limited Scleroderma [limited to skin involvement] + other CREST Manifestation: Calcinosis Raynoaud's Esophageal dysmotility Sclerodactyly Telangiectasia
Hyperketaosis with retention of nuclei in stratum corneum
Psoriasis [+ increased thicness of stratum corneum]
“mask of prregnancy” or OCP use
- dark cheeks
Melasma
White person who can’t tan
Autoimmune destructino of mealnocytes [Vitiligo] <- obvious in darker skinned folks.
Superficial dermal edema & lymphatic channel dilation
Urticaria/Hives
Sudden apperance of multiple seborrheic keratoses [indicating an underlying malignancy of GI or lymphoid]
Leser Trelat Sign
Collections of neutrophils within the stratum corneum
Monro microabscesses
Honey colored crusting
Impetigo [Staph aureus or Strep Pyogenes]
Crepitus from methane/CO2 production + bullae and purple skin
“Flesh eating bacteria”= Necrotizing Fascitis from anaerobic bacteria or Strep pyogenes
Generalized red rash with sloughing of the UPPER layers of the epidermis that heals completely seen in newborns/children
Staph Scaled Skin Syndrome [exototoxin destroy keratinocytes attachments in the stratum granulosum only]
White painless plaques on tongue that can NOT be scraped off
EBV mediated hairy leukoplakia [vs. oral thrush/candidiasis]
*Link to HIV pts
Firm, pink paules with dimpled {milky fluid filled] center
Mollucsum contagiosum mediated by POX virus
POX Virus= enveloped, dsDNA virus
Positive Nikolsky sign [seapration fo epidermis upon manual stroking of skin] + IF revealing Abs around epidermal cells in a reticular [net like] pattern
Pemphigus Vulgaris
Tense blisteres that contain eosinophils; affects skin but SPARES ORAL MUCOSA, Negative Nikolsky sign
Bullous Pemphigoid
IgA deposits at tips of dermal papillae associated with celiac disease
Dermatitis herpetiformis
Fever, Bulla formation, necrosis and sloughing of skin [high mortality rate like sloughing] - usually involves at least two mucosal membranes
Stevens Johnson syndrome [linked to adverse drug rxns]
What determines risk of SCC from Acitnic keratosis?
Risk ir proportional to degree of epithelial dysplasia
Painful, inflammatory lesions of subcutaneous fat usually on anterior shins
Erythema nodosum
Pruritic Purple Polygonal Planar Papules and Plaques with Wickham striae [reticular white lines] and Sawtooth infiltrate of lymphocytes at DERMAL EPIDERMAL JUNCTION
Lichen Planus [associated with Hepatitis C]
Herald Path on hair line that progresses to “Christmas tree” distribution on back
Pityriasis Rosea
Pin pearly nodules with palisading/ straight lined nuclei
Basal cell carcinoma
cup-shaped tumor with keratin debris in the center/dimple, grows rapidly but may regress spontaneously
Keratoacanthoma [a variant of Squamous cell carcinoma]
BRAF kinase mutation with positivity for S-100 tumor marker
Melanoma [risk of malignancy linked to depth of invasion]
Neutrophil chemotactia agent
LTB4
Inhibition of platelet aggregation and promotion of vasodilation
PGI2
Increased bleeding time via irreversible inhibtion of COX1 and 2 via covalent aceytlation but no effect of PT/PTT
Aspirin
Side effect: hepatic necrosis from depletion of glutathione and formation of toxic adducts in the liver
Acetaminophen
Side effect: Corrosive esophagitis and osteonecrosis of the jaw if that patient doesn’t take the drug w/ water and remain upright for at least 30 mins afterward…
AlenDRONATE [Bisphosphonate]
MOA: inhibition of osteoclast via hydroxyapatite binding in bone
Acute Gout Rx
NSAIDS [Naproxe or Indomethacin], Glucocorticoids or Colchicine [MOA: stabilizes tubulin to inhibit Microtubule polymerization and impair leukiocyte chemotaxis and degranulation— has GI side effects]
Rx for Chronic Gout and Tumor lysis syndrome [blocks the urate nephropathy]
+ increases concentrations of chemo agents: Azathioprine and 6-MP
Allopurinol [blocks Xanthine to Uric Acid conversion]
*Febuxosat also inhibits xanthine oxidase
Rx to knock out P-acnes for Rx of Acne Vulgaris
Benzoyl Peroxide
Significant herniation of cerebellar tonsils and vermis through foramen magnum with aqueductal stenosis and hydrocephalus
Px: lumbosacral myelomeningocele and paralysis below the defect
Chiari 2 [Arnold Chaiari malformation]
Headache, cerebellar signs + “cape like” bilateral loss of pain and temperature sensation in UE w/ preservation of fine touch sensation
[Most commonly affecting C8 to T1]
Syringomyelia [cystic cavity within spinal cord]
Physical support to CNS, repair, Potassium [K+] metabolism & removal of excess neurotransmitter, component of BBB, reactive gliosis in response to neural injury
+GFAP
Astrocyte [from neuroectoderm]
Decreased time constant and Increased length constant [directly]
MYELIN
Which viruses make use of RETROGRADE peripheral MOTOR nerves to attack CNS?
Polio
Rabies
Tetanus
Which viruses make use of RETROGRADE peripheral SENSORY nerves to attack CNS?
HSV
Slow unmyelinated fibers in all skin and some viscera for dull PAIN AND WARM TEMPERATURE
C fibers
Fast, myelinated fibers in all skin and some viscera for SHARP PAIN and cold temps
A delta fibers
large myelinated fibers that adapt quickly in hairless skin [palms and soles] for fine/light touch and proprioception
Meissner Corpuscles
Large myelinated fibers in deep skin layers, ligaments and jionts for VIBRATION and pressure
Pacinian corpuscles
Large myelinated fibers that adapt SLOWLY in basal skin layer and hair follicles for pressure, deep touch and proprioception
Merkel discs
Synthesized in Locus cerules
Up in anxiety and Down in Depression
NE
Synthesized in Ventral tegmentum and Substantia Nigra
Down in Parkinson and Depression
Up in Huntingtons
DOPAMINE
Synthesized in Raphe nucleus [pons, medulla and midbrain]
Up in PD
Down in anxiety and depressionq
5-HT/ SEROTONIN
Basal nucleus of Meynert
Up in PD
Down in AD and Huntingtons
Ach
Nucleus Accumbens
Down in anxiety
Down in Huntington’s
GABA
Hypothalmic nucleus that’s inhibited by LEPTIN and is destroyed, leads to ANOREXIA
Lateral Nucleus
Hypothalmic nucleus that is under SYMPATHETIC control and controls body HEATING
Posterior Nucleus
What drugs DECREASE REM Sleep?
Depressants [Alcohol, Benzo and Barbituates] <– these decrease delta wave sleep too
+ Norepi decreases REM sleep as well
Rx for bedwetting
Oral desmopression [ADH mimic] OR Imipramine
Rx for night terrors/sleepwalking [occurs during Stage N3 - delta, slow wave sleep]
Benzos
“It’s like anxiety sleep disorders”
Receives motor input from Basal ganglia and Cerebellum in order to modulate movement and send corrections to precentral gyrus/motor cortex
VL {ventral lateral} nucleus of the Thalamus
Disinhibition fo Subthalamic Nucleus via GPe leading to stimulation of GPi/SN to inhibit the thalamus and decrease motion
INDIRECT Basal Ganglia pathway [Dopamine inhibits this thereby producing movement]
Lewy Bodies
composed of alpha synuclein which are intracellular eosinophilic inclusions [PD]
Which nucleotide encodes polyglutamine leading to anticipation effect and onset of choreiform movements, aggression, depression and dementia?
CAG
Blepharospam [sustained eyelid twitch] is an example of what type of movement disorder?
Dystonia [sustained involuntary muscle contractions]
Rx for essential tremor: NOT ALCOHOL [which so many pts try} but…
Beta blockers or Primidone
Which virus is linked to Kluver Bucy syndrome and which part of the brain is affected?
HSV-1, bilateral amygdala
Spatial neglect syndrome
Lesion to right parietal-temporal cortex
Agraphia, Acalculia, Finger Agnosia and left-right disorientation
Left parietal Temporal cortex lesion [called Gerstmann Syndrome]
Reduced levels of arousal and wakefulness
Reticular Activating System lesion in the midbrain
Truncal ataxia, postural issues and dysarthria [difficulty speaking]
Cerebellar vermis lesion
Lesion to this structure cause eyes to look AWAY from the side of the lesion
Paramedian Pontine Reticular Formation lesion
Lesion to this structure causes eyes to look TOWARD the side of the lesion
Frontal eye fields lesion
Overly rapid correction fo hyponatremia
Central Pontine Myelinolysis [ “locked in syndrome”]
Damage to arcuate fasciculus
Conduction aphasia [Can’t repeat; fluent speech and intact comprehension though]
Aphasias with GREAT repetitions just other issues… [3]
- Trancortical motor: can’t produce
- Transcortical sensory: can’t understand; doesn’t make SENSE
- Mixed transcortical: all you’ve got is repetition
Therapeutic hyperventilation
To decrease CO2 and decrease itnracranial pressure in cases of acute cerebral edema [stroke, trauma] via decrease in cerebral perfusion by vasoconstriction
Lesion of PICA
Nucleus ambiguous effects: hoarseness and dysphagia & decreased gag reflex too
Lesion of AICA
Facial doop, supplies facial nucleus specifically
Injury to basilar artery
Locked in Syndrome
Berry Aneurysms associated with which conditions [3]
ADPKD, Ehlers-Danlos Syndrome & Marfan’s
Previous stroke patient with intitial sensation fo numbness and tingling followed in weeks to months by allodynia [ordinarily painless stimuli cause pain} and abnormal sense of touch
Central post stroke pain syndrome linked to unresolved thalamic lesion
Complication of tonsillar herniation
Cardio pulmonary arrest [cerebellar tonsils thru foramen magnum that can compress brainstem]
Complication of subfalcine herniation
Compression of ACA leading to infarction
[cingulate gyrus thru falx cerebri
Complication of uncal herniation
Issues with structures in the tentorium cerebelli [CN 3, PCA and paramedian artery]
- temporal lobe/uncus goes beneath the tentorium cerebelli
Subdermal hematoma [causing midline shift] , retinal hemorrhage & cerebral edema
Shaken Baby Syndrome/Child abuse
Risks associated with subarachnoid hemorrhage
Vasospasm [due to blood breakdown- must be treated with nimodipine]… and also risk of re-bleed [visible on CT]
Bright area on noncontrast CT post stroke
Hemorrhagic stroke- DO NOT give tPA!
Bright on MRI
Ischemic stroke
What’s in the cavernous sinus?
ICA, CN 3, 4, V1 and V2, 6
*6 most likely injured
From cavernous sinus, where does the venous blood go?
If Sup. petrosal sinus–> Transverse Sinus –> Sigmoid Sinus –> IJV
If Inf. petrosal sinus –> IJV [direct!]
Which minerals are HIGHER in the CSF in comparison to blood?
Chloride and Magnesium [everything else is lower in CSF- in NORMAL/ non-ill situations]
Which mineral is EQUAL concentration in CSF and blood?
Sodium
Urinary incontinence, ataxia and cognitive dysfunction “Wet, Wobbly and Wacky”
Normal pressure hydrocephalus [ expansion of ventricles that distorts the fibers of the corona radiata ; issue is with the arachnoid villi, low absorption]
Normal CSF pressure but dilated ventricles
Hydrocephalus ex vacuo [relative increase in CSF/ventricle size due to atrophy of rest of the brain
“Floppy baby”- no honey though. Inherited degeneration of ventral horn/LMN
Werdnig-Hoffman disease leading to flaccid paralysis
-Auto Recessive inheritance
Combined UMN and LMN deficits with no sensory, cognitive or oculomotor deficitis - what’s the mutation in familial cases?
Superoxide dismutase 1/ ALS
Rx for ALS
Rilouzole [decreases presynpatic glutamate release]
Complete occlusion of Anterior spinal artery, what areas are affected? what areas are spared?
Affected: Corticospinal tract & Spinothalamic tract
Spared: Dorsal columns and Lissauer tract
Impaired sensation and proprioception and progressive sensory ataxia from degeneration/demyelination of dorsal columns and roots
Tabes dorsalis [Tertiary syphilis]; Charcot joints, shooting pain, ARGYLL ROBERTSON PUPILS, — absent DTRs and positive Romberg sign
demyelination fo dorsal columns, lateral corticospinal tracts and spinocerebellar tracts
Subacute combined degeneration [Vit B12 or Vit E deficiency]
Virus causing destruction of cells in anterior horn of spinal cord leading to LMN sign PLUS signs of infection [malaise, headache, fever, nausea]
POLIOmyelitis [CSF shows increased WBCs and slight increase in protein but no change in glucose bc it’s viral] — polio replicates in oropharynx and small intestine
Staggering gait, frequent falling, nystagmus, pes cavus/caved in chest, hypertrophic cardiomyopathy, kyphoscoliosis in childhood
Friedreich ataxia [GAA tri nuc repeat] on chromosome 9
; encodes frataxin [iron binding protein] that leads to impairment in mitochondrial functioning
2 ipsilateral sx and 1 contralateral sx [linked to spinal lesions]
Brown-Sequard Syndrome [hemisection of spinal cord]
- Ispilateral: UMN signs below lesion, LMN at level of lesion
- Contralateral: Pain and temp loss
Reflex: s3, s4
Anal wink
Reflex: C7
Triceps reflex/ Radial nerve
Reflex: L3/4
Patella/ Quadriceps/ Femoral Nerve
Reflex: S1/2
Achilles/ Gastrocnomes m/ Tibial nerve
CN that lie in the midline of the brain stem
CN 3, 6 and 12
[Motor= medial]
Paralysis of conjugate vertical gaze
Lesion in superior colliculi/ Parinaud Syndrome [Ex: a pinealoma]
Jaw Jerk reflex
V3- Masseter muscle control both sensory and motor component of the reflex
Cranial exit: Superior Orbital Fissure
CN 3, 4, V1, 6 + opthalmic vein and sympathetics
Cranial exit: Foramen Rotundum
V2
Cranial exit: Foramen Ovale
V3
Cranial Exit: Internal Auditory Meatus
CN 7 and 8
Cranial Exit: Jugular Foramen
CN 9, 10, 11
Opthalmoplegia and decreased corneal and maxillary sensation with NORMAL VISUAL ACUITY
Cavernous sinus syndrome
Jaw deviates toward side of lesion
CN 5 motor lesion [due to unopposed pterygoid muscle]
The thin and rigid cochlea located at the BASE picks up this type of sound
High frequency sound [high frequency is also what’s loss first!]
Contralateral paralysis fo LOWER FACE, forehead spared
UMN of facial nerve lesion
Ipsilateral paralysis of upper AND lower face
LMN of facial nerve lesion
Child with white pupil and trouble with visual tracking +/- tumors in eyes
Retinoblastoma [remember link to osteosarcoma]
Uveitis [inflammation of uvea/iris with sterile pus and redness] often linked to:
Systemic inflammatory disorders:
-sarcoid, rheumatoid arthritis, juvenile arthritis, TB, HLA-B27 issues, etc.
Retinal edema and necrosis leading to scar
Retinitis
[usually VIRAL cause- CMV [if AIDS patients], HSV or HZV]
Acute, painless monocular vision loss with cherry red spot at the fovea
Central retinal artery occlusion
*can link to Temporal arteritis
Retinal hemorrhage and edema
Retinal vein occlusion
Pt with DM with retinal damage due to chronic hyperglycemia
If proliferative; means chronic hypoxia lead to new blood vessel formation with resultant TRACTION on retina- must treat with anti-VEGF injections
Very painful, sudden vision loss, halos around lights, rock hard eye, frontal headaches
Acute closure glaucoma - so NOT give epinephrine because of it’s mydriatic effect
Painless, bilateral, opacification of lens paired with decrease in visual acuity
Cataracts
Causes:
-being old, smoking, alcohol, prolonged steroid use, galactosemia, GLACTOKINASE DEFICIENCY, DM [sorbitol accumulation], trauma, infection
Enlarged blind spot, elevated optic disc with blurred margins seen on fundoscopic exam
Papilledema
Eye looks down and out plus ptosis, pupillary dilation and loss of accommodation
CN 3 damage
Eye moves upward + head tilt toward side of the lesion [will try to compensate by tilting head in opposite direction]- problems going down the stairs
CN 4 damage
To test Inferior Oblique m
Have pt look up
Decreased bilateral pupillary constriction when light is shone in affected eye relative to unaffected eye
Marcus Gunn Pupil
Dx via “Swinging flashlight test”
Break between neurosensory layer [photoreceptor layer] and outermost pigmented epithelium [normally shield excess light]- most common in patients with high myopia and are often preceded by posterior vitreous detachment [flashes/floaters] with eventual monocular loss of vision [“curtain drawn down”
Retinal detachment
Lesion to the right temporal [more lateral radiations] of the MCA
Left upper quadrant anopia
Lesion to the right parietal [more medial radiations] of the MCA
Left lower quadrant anopia
PCA infarct [on right]
Left hemianopia with macular sparing
With Internuclear Opthalmoplegia, what part of motor vision is NORMAL?
Convergence
Ascending [motor] Paralysis, Loss of DTRs, Autonomic dysfunction, increased protein in CSF but normal WBC
Guillain-Barre
- autoimmune disease linked to GI or respiratory infection with Camplobacter Jejuni or CMV
- MOA= molecular mimicry/ type 4 HSN
What TWO anterior pituitary hormones are stimulated by TRH release from the hypothalamus?
TSH and Prolactin
HTN, Hypokalemia, Low DHT leading to ambigious genitalia in XY person and lack of secondary sexual development in XX person
17 alpha hydroylase deficiency
Low Cortisol, Low Androgen, High Aldosterone
HYPOtension, HYPERkalemia, Increased Renin, Increased 17 hydroxy progesterone
21 hydroxylase deficiency
Presents as salt wasting in infancy or precocious puberty in childhood [virilization in XX/girls]
Hypertension due to high 11 deoxycorticosterone, Virilization in XX person only
11 Beta Hydroxylase deficiency
Signaling pathway: cAMP [7]
“FLAT ChAMP”
FSH, LH, ACTH, TSH, CRH, hCG, ADH [V2 receptor/ the one linked to antidiurectic effect!]
- all of the basophilic hormones of the ant. pituitary
+ CRH, hCG and ADH
Signaling pathway: cGMP [2]
Vasodilators!
-ANP, NO [and EDGF]
Signaling pathway: IP3 [7]
“GOAT HAG”
GnRH, Oxytocin, ADH [V1 receptor], TRH
Histamine [H1], Ang II, Gastrin
Signaling pathway: Steroid receptor/ Nuclear
VETTT CAMP
Vit D, Estrogen, Testosterone, T3/T4
Cortisol, Aldosterone, Progesterone
*Adrenal gland hormons [aldosterone, cortisol, androgens] + thyroid + Vit D
Signaling pathway: Intrinsic Tyrosine Kinase- MAP Kinase
Insulin + Growth Factors!
IGF-1, FGF, PDGF, EGF
Signaling pathway: Receptor-assocaited tyrosine kinase- JAK/STAT pathway
Acidophiles: GH & Prolactin
+
Cytokines: IL2, IL 6, IL 8, IFN
Autosomal dominant unresponsiveness of kidney to PTH. Hypocalcemia, shortened 4th/5th digits, short stature
Pseudohypoparathyroidism/ Albright Osteodystrophy
Greater than 50% increase in urine osmolarity after water restriction test
Central Diabetes Insipidus
Large tongue, deep voice, coarse facial features, impaired glucose tolerance/insulin resistance
Acromegaly [cardiac failure= COD, Rx/ with octreotide]
Aldose reductase
Glucose to Sorbitol
Sorbitol dehydrogenase
Sorbitol to fructose
Cause: Excess fat breakdown and increase in ketogenesis from increase free fatty acids esp after stress/infection [due to increased insulin requirements- but person is diabetes/ type 1]
DKA [the ketogenesis from the increased fatty acids are turned into ketone bodies [beta hydroxybutyrate and acetoacetate]
Kussmaul respirations, GI sx, psychosis/delirium, dehydration, fruity breath odor
DKA
Labs: Hyperglycemia, increases hydrogen ions, decreased bicarbonate [anion gap metabolic acidosis], hyperkalemia [but depleted intracellular potassium due to transcellular shift from decreased insulin]
DKA
Rx: IV fluids, IV insulin and potassium
Islet leukocytic infiltrate
Type 1 DM
Islet amyloid polypeptide deposits
Type 2 DM
Tumors of Parathyroid, Pituitary, Pancreas + usually Px with kidney stones and stomach ulcers
MEN 1
Medullary thyroid cancer, pheochromocytomas and parathyroid hyperplasia
MEN 2 A [ret linked]
Meudllary thyroid cancer, pheochromocytomas and oral/intestinal ganglioneuromatosis/ mucosal neuromas + pt usually has marfanois habitus
MEN 2 B [ret linked]
Part of Gram negative bacteria that induces IL1 and TNF/ antigen
Lipid A of outer membrane/ O polysaccharide is the official antigen
Part of Gram positive bacteria that induces IL1 and TNF/antigen
Lipoteichoic acid of the cell wall/cell membrane
D glutamate capsule
Bacillus anthracis [the rest of the capsules are polysaccharide]
Contain sterols and have no cell wall
Mycoplasma
Contain mycolic acid and have high LIPID content
Mycobacteria
Bugs that do not stain well with gram stain
"These Microbes May Lack Real Color" Treponema [too thin to see] Mycobacteria [acid fast stain w carbolfuschin- detects lipid] Mycoplasma [no cell wall] Legionella [intracellular] Rickettsia [intracellular] Chylamydia [intracellular]
PAS stain
glycogen- T. Whipple Disease
Giemsa Stain
Ugh. “Certain Bugs Really Try My Patience”
Chylamidia Borrelia Rickettsiae -- Plasmodium
Carbol fucsin stain/ ACID FAST- picks up lipid
Nocardia
Mycobacteria
India Ink
Cryptococcus neoformans
Red stain on Mucicarmine stain
Cryptococcus neoformans [the red= thick polysaccharide capsule]
Silver Stain
H.Pylori Loves Funky Silver
H.Pylori
Legionella
Fungi
Thayer Martin Agar
VPN!!! Vancomycin, Polymyxin, Nystatin
Inhibits everything but Niesseria!
Vanc blocks positives
Polymyxin blocks all the negatives except Niersseria, ofcourse.
Tellurite Agar
Cornybac Diptheriae
Which bacteria has an agar that requires CHOLESTEROL in order for growth?
Mycoplasma pneumoniae {Eaton Agar}
Charcoal yeast agar with IRON and CYSTEINE
Legionella [remember… legion of soldiers by the charcoal fire with their iron hats. They aren’t sissies!]
Obligate Aerobes
“Nagging Pests MusBreathe”
Nocardia
Pseudomonas
Mycobacteria
Obligate Anaerobes
“Can’t Breathe Air”- y? they lack catalase/superoxide dismutase and are therefore susceptible to oxidative damage so they just avoid O2 completely!
Clostridium
Bacteriodes
Actinomyces
… AminO2glycosides are ineffective against these bc AminO2glycosides require oxygen to enter into bacterial cell
Antiphagocytic Capsules/Encapsulated bacteria
SHiNE SKiS
Salmonella
H. Influenzae [anti cap vaccine]
Neisseria [anti cap vaccine]
E.Coli
Strep Pneumo [anti cap vaccine]
Klebsiella Pneumo
Step Agalactie [GBS]
NO SPLEEN!?! uh-oh. You’re popped with these.
Catalase Positive Bugs
“CP SALES”
Candida
Pseudomonas
Staph Aureus Aspergillus Listeria E.Coli Serratia
Urease positive Bugs
“PS CHUNKS”
Proteus
Staph Epidermidis
Cryptococcus H.Pylori Ureaplasma Nocardia Klebsiella Staph Sapro
Yellow Sulfar Granules
Actinomyces Israelii
Gold/Yellow Pigment
Staph Aureus
Greenish/Blueish Pigment
Pseudomonas
Virulence: Protein A- Binds Fc region of IgG to prevent opsonization and phagocytosis
Staph Aureus
Virulence: IgA Protease- cleaves IgA antibody in order to colonize respiratory mucosa
“SHiN”
Step Pneumo
H. Influenza
Neisseria
Virulence: M Protein- to prevent phagocytosis
Group A Strep [Strep pyogenes]
- leads to molecular mimicry and Rheumatic Fever
Exotoxin MOA: Inactivate Elongation Factor [EF-2] via ADP ribosylation to inhibit protein synthesis
DIptheria Toxin [Coryne Diphtheriae] & Exotoxin A [Psuedomonas]
Exotoxin MOA: Inactivate 60 S host ribosome by removing adenine from rRNA to inhibit protein synthesis
Shiga toxin [Shigella] and Shiga-like toxin [EHEC]
Exotoxin MOA: Overactivate adenylate cyclase and wildly increase cAMP leading to secretion of Cl- in gut with water following
ETEC- Heat labile toxin
Bacillus Anthracis
Cholera Toxin
Exotoxin MOA: Overactivate guanylate cyclase and wildly increase cGMP leading to decreased reabsorption of NaCl/Water= increased fluid secretion
ETEC-Heat stable toxin
Exotoxin MOA: Overactivates adenylate cyclase by disabling Gi, impairing phagocytosis to permit survival of microbe
Pertussis toxin
Exotoxin MOA: Has proteases that cleave SNARE protein required for NT release
Tetanospasmin [impairs GABA and glycine]
Botulinum toxin [impairs Ach]
AB Toxins
Diptheria, Exotoxin A, Shiga + Shiga/Like, Heat Labile ETEC, Cholera toxin and Pertussis toxin
Exotoxin MOA: has a Phospholipase [called lecithinase] that degrades tissue and cell membranes
Alpha toxin [Clostridium perfringens]
Exotoxin MOA: has a protein that degrades cell membrane
Streptolysin O [Strep pyogenes/ Group A Strep]
Exotoxin MOA: Bring MHC 2 and TCR in proximity to outside of antigen binding site to cause overwhelming release of IFN gamma and IL2 leading to shock
Toxic Shock Syndrome Toxin [Staph Aureus]
Exotoxin A [encoded by lysogenic phage]- [Strep pyogenes]
Bacterial toxins that are encoded in lysogenic phage
ABCDE
shigA like toxin [EHEC] Botulinum Toxin Cholera Toxin Diptheria Toxin Erythrogenic toxin [the Exotoxin A of Strep pyogenes]
Ability to take up naked DNA
Transformation
SHiN
Strep Pneumo
H. Flu
Neisseria
Helps bacteria pass Ab resistance genes
Conjugation
Fertility Factor = plasmid transfer only
High frequency Recombination cell= plasmid & chromosomal transfer
Segment of DNA called a transposon that can be excised and reintegrated from one location to another
Transposition
Can synthesize dextrans from glucose
Strep Viridans [alpha hemolytic, optochin resistant, bile INsoluble Gram positive]
Red sandpaper rash and bright red/ “strawberry” tongue
Scarlet Fever
-Strep pyogenes
Colonizes the vagina and causes pneumo, meningitis and sepsis in babies- Should prophalactically give mom penicillin
CAMP FACTOR= expands hemolytic area of strep
Test will be positive for Hippurate
Strep Agalactiae [GBS]
Beta Hemolytic Bacteria
GAS and GBS
+ Staph Aureus
+ Listeria
MOA: actin rockets/ tumbiling motility allows them to escape capture by antibody- must kill using cell-mediated death
Listeria
Forms fibrin clot around itself promoting abscess formation
Staph {aureus}
Spore forming bacteria
Clostridium
Bacilis
Coxiella
*at end of stationary phase when nutrients are limited; highly resitant to heat and chemicaly [due to dipicolinic acid which allows the bacteria to pump all of the water out of cells]; must autoclave to kill spores [think surgical equipment]
Most specific test for TB
Interferon Gamma release assay [fewer false positives]
These bacteria have CORD FACTOR which inhibits macrophage maturation and induces release of TNF-alpha
Mycobacteria
[they have sulfatides/surface glycoproteins, too, which inhibit phagolysosomal fusion]
Must give this along with Rx Gonorrhoeae in order to guard against possible Chlamydia co-infection
Azithromycin or Doxycycline
The vaccine for this bug contains tye B capsular polysacc [polyribosylribitol phosphate-PRP] conjugated to diptheria toxoid
H. Influ
E.Coli virulence: Fimbria
UTI
E.Coli virulence: K. Capsule
Pneumonia
Neonatal Meningitis [Px: fever, baby won’t eat]
E.Coli virulence: LPS Endotoxin
Septic Shock
Which of the E.Coli’s does NOT ferment sorbitol?
EHEC
Malignant otitis externa in a Pt with DM
Pseudomonas
Rose spots on belly + fever + this bug will be in the gallbladder of known carriers
Typhoid Fever
-Salmonella [Gram negative, non lactose fermenting, oxidase negative rod with flagella]
- Hydrogen sulfide will be produced
RLQ pain that mimicks Appendicitis, usually proceeded by a sore throat and pt. reports some ingestion of pet feces contaminated milk or pork
Yersenia
[Gram negative rod- lactose and oxidase negative]
What does E. Coli produce that allows it to break down lactose into glucose and galactose?
Beta galactosidase
The gram negative outer membrane layer inhibits entry of which antibiotics?
Penicillin G and Vancomycin
[some gram negatives are still susceptible to Ampicillin and amoxicillin though]
Ferments glucose AND maltose [vs it’s partner who just ferments glucose]
Neisseria Meningitidis
This bug is linked to air conditioning filters being dirty and labs show hyponatremia.
Legionella
Chronic psuedomonas caused pneumonia in cystic fibrosis patients is associated with…
BIOFILM
Which of the E.Coli’s doesn’t produce a toxin?
EPEC-
causes pediatric diarrhea via adherence via pedastel; just flattens villi thereby decreasing reabsorption and causing increased secretion of fluids
Anemia, Thrombocytopenia and acute renal failure
Hemolytic uremic syndrome [link to schistocytes]
Spirochetes
“BLT”
Borrelia
Leptospira
Treponema
Flu like symptoms plus jaundice, photophoia, red conjuctiva without exudate + Hx of contact with water in which an animal may have urinated in
Leptospira
Facial nerve palsy, Arthritis, Third degree heart block and Erythema migrans
Borrelia/ Lyme Dz
Non specific test for Treponema
VDRL/RPR
Specific test for Treponema
FTA-ABS
Saber shins, saddle nose, CN 8 deafness and Hutchinson teeth
Congenital Syphilis
VDRL
detects nonspecific antibody that reacts with cardiolipin [inner mito membrane/ NRG metabolism]
- False positive: VDRL- Viruses, Drugs, Rheumatic Fever, Lupus/Leprosy
Cat scratch
Bartonella
Cat/Dog BITE
Pasturella
Treatment for all Rickettsial Diseases
Doxycycline
Rash starts at wrists/ankles and spreads to trunk, palms, soles
Rocky Mountain Spotted Fever/ Rickettsia Rickettsii
[intracellular, can’t synthesize ATP]
Rash starts at the trunk and spreads outward but spares palms and soles
Rickettsia TYPHUS
Neonate with staccato cough and conjunctivitis
Chlamydia trachomatis types D-K
Pt comes in for insidious onset of headache, nonproductive cough and diffuse interstitial infiltrate. X-ray looks much worse than pt. High titer of cold agglutinins [IgM]
Mycoplasma Pneumoniae [walking Pneumo]- treat with azithromycin
Methylation of Histone
Mostly makes DNA Mute/ Inactive
Acetylation of Histone
Makes DNA active
Temporary base used in the synthesis of Pyrimidines
Orotic acid
Two metabolic pathways that use Carbamoyl Phosphate
De novo pyrimidine synthesis pathway
Urea Cycle
T cells low, but B cells normal + increased renal excretion of purines
PNP [Purine Nucleoside Phosphorylase] deficiency- less severe than ADA deficiency
Increase renal excretion of uric acid
Probenecid/Sulfinpyrazone
Excess of ATP and dATP leading to inhibition of DNA synthesis and decreases lymphocyte count
Adenosine deaminase deficiecy [SCIDS]
Increased Adenosime and dAdenosine leading to decreased RIbonuc Reductase & decreased T cells, B Cell, NK Cells +Underdeveloped Thymus
Excess uric acid production and de novo purin synthesis bc Amidotransferase no longer being inhibited [due to absent HGPRT enzyme]
Px: intellectual disability, self-mutilation, aggression, hyperuricemia, gout, dystonia
Rx: Allopurinol or Febuxostat
Lesch Nyhan Syndrome
Degradation of RNA primer via 5’ to 3’ exonuclease and replacement with DNA
DNA Poly I
3’ to 5’ Proofreading activity plus adds the nucleotides
DNA Poly III
RNA dependent DNA poly that adds DNA to 3’ end in order to avoid loss of genetic material with every duplication
Telomerase [increased levels in cancer cells]
Which DNA Repair Mechanism occurs in the G2 phase?
Mismatch repair [linked to HNPCC]
UV damage causes thymine dimers that are repaired by this
Nucleotide Excision Repair [G1]- Xeroderma Pigmentosum= deficiency
How do toxic mushrooms/ Amanita Phalloides/ alpha amanitin cause liver failure/severe hepatotocity?
inhibition of RNA polymerase II [mRNA]
This RNA Poly makes the type of RNA that’s made in the nucleolous
RNA Poly 1 [rRNA]
Protein factor sigma
Initiation of prok transcription
Protein factor Rho
Termination of prok transciption
“P bodies”
Police the mRNA- contain exonucleases, decapping enzymes and micro RNAs- also they’re able to store unused mRNA for future translation
Order of the “process” of taking initial transcript hnRNA to mRNA [occurs in the nucleus
Capping of 5’ end [7 meth cap] end
Splicing out of introns
Anti Smith antibodies
Antibodies to spliceosomal snRNPs [highly specific for SLE]
T Arm of tRNA molecule
Thymine, Pseudouridine and Cytosine
*Necessary for ribosome binding
D Arm of tRNA molecule
Dihydrouracil necessary for tRNA recognition by correct aminoacyl tRNA synthetase
How many high NRG bonds are used/ protein synthesis cycle?
FOUR
ATP- tRNA activation
GTP- initiation of protein synthesis/ translocation
Inhibition of protein synthesis via cutting 28 S rRNA during elongation phase
Shiga Toxin
Inhibition of Peptidyl transferase leading to inhibition of protein chain elongation
Chloramphenicol [antibiotic]
Inhibition of protein initiation complex [30S]
Aminoglycosides [gentamicin, neomycin, tobramysin]
Inhibition of translocation of ribsome during the elongation phase [50s]
Macrolides [- thromycin]
Clindamycin
Normal inhibition of G1 to S progression [and mutations in these genes result in unrestrained cell division]
p53
hypophosphorylated Rb
Permanent cells: Remain in G0 phase; regenerate from stem cells only
Neurons
Skeletal Muscle
Cardiac Muscle
RBCs
Stable cells: Enter G1 from G0 only when stimulate
Hepatocytes
Lymphocytes
Nephrons [?]
Labile cells: Never go to G0; divide rapidly with a short G1 phase. These cells are most affected by chemotherapy [although of the WBCs, lymphocytes are first affected…]
Bone Marrow cells Gut epithelial cells Skin cells Hair follicles Germ cells
Free ribosomes
Unattached to any membrane; site of synthesis of cytosolic and organellar proteins
Specifically:
cytosolic proteins and mitochondrial proteins are translated by free ribosomes
Steroid hormone synthesis, detoxification and lack surface ribosomes
+ sequesters and releases Ca2+
SER
Defect in phosphotransferase enzyme leading to inability to add mannose phosphate to proteins for trafficking to lysosomes
I-Cell disease= proteins are secreted extracellularly rather than delivered to lysosomes
Px: Coarse facial features, clouded corneas, joint issues, high plasma levels of lysosomal enzymes
Signal Recognition Particle [SRP]
Protein in the cytosol that traffics proteins from the ribosome to the RER
If absent –> proteins accumulate in the cytosol
Trafficking proteins: COP 1
Retrograde golgi transport OR Golgi –> ER
Trafficking proteins: COP 2
Anterograde golgi transport OR ER –> Golgi
Membrane enclosed organelle, contains catalse, catabolism of very long chain fatty acids, branched chain fatty acids and amino acids
Peroxisome
Drugs that target microtubules
“Microtubules Get Constructured Very Poorly”
Mebendazole [anti helminithic] Griseofulvin [anti-fungal] Colchicine [anti-gout] Vincristine/Vinblastine [anti-cancer] Paclitaxel [anti-cancer]
Intermediate filament: Vimentin
Connective TIssue
Collagen Synthesis: Issue with hydroxylation
Vit C deficiency –> scurvy
Collagen Synthesis: Issue with Glycosylation leading to no triple helix formation
Osteogenesis imperfecta [defect of Collagen Type 1]
Collagen Synthesis: Issue with Cross linking
Ehlers Danlos Syndrome
Before procollagen undergoes proteolytic processing and cross linking; but after syntehsis, hydroxylation and glycosylation… what must happen?
Procollagen must be exocytosed into extracellular space [pushed out of fibroblast]
Ehlers Danlos Syndrome is an example of what type of Genetic phenomenon?
Locus heterogeneity
Connective tissue dz caused by impaired COPPER absorption and transport leading to decreased activitiy of lysyl oxidase
Px: BRITTLE, KINKY HAIR- growth retardation, and hypotonia
Menkes Dz
This is a glycoprotein that forms a sheath around elastin; if there’s a defect in this glycoprotein you get Marfan’s
Fibrillin [type of elastin]
This blotting procedure is useful for studying mRNA levels which are reflective of gene expression
Northern Blot
This blotting technique is use to identify DNA-binding proteins [Ex: transcription factors] using labeled oligonucleotide probes
Southwestern Blot
Able to detect SNPs and copy number variations [useful for genotyping, genetic testing and forensics]
- scanner detects relative amounts of complementary binding [DNA OR RNA probes can be used]
Microarrays
This system can manipulate genes are specific developmental points
Cre-lox system
Synthesis of a dsDNA that separates and promotes degradation of target mRNA thereby “knocking down”/interfering with gene expression
RNA interference
Karyotyping stains chromosomes in what phase of mitosis?
Metaphase
For cloning, restriction endonucleases cut the sample DNA where?
Palindrome sequence
Benefit of using cytoplasmic mRNA instead of genomic/chromosomal DNA for cloning?
cDNA/cytoplasmic mRNA have entire reading frame in tact- vs. genomic which has some introns too. So if you want to study introns, should use the chromosomal DNA
One gene contributes to multiple phenotypic effects
Pleiotropy
Ex: PKU [light skin, retardation, musty body odor]
If a patient inherits a mutation in a tumor suppressor gene, the complementary allele must be deleted before cancer develops
Loss of heterozygosity
Ex: Retinoblastoma
A mutation of a transcription factor in it’s allosteric site leading to a nonfunctioning mutant that prevents the normal gene product from functioning
Dominant negative mutation effect
Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance; based on POPULATION- not just within your family!
Linkage disequilibrium
Mitotic errors after fertilization leading to presence of genetically distinct cell lines in the same individual
Mosaicism
Mutations at different loci producing a similar phenotype
Locus heterogenity
Different mutations in the same locus produce the same phenotype
[so the mutation is what’s different… not the locus.]
Allelic heterogeneity
Presence of both normal and mutated mtDNA resulting in variable expression in mitochondrial inherited disease
Heteroplasmy
Let’s say a person expresses a phenotype for a RECESSIVE disorder, but only one parent is a carrier…
Uniparental disomy
- offspring receives2 copies of chromosome from 1 parent and no copies from the other
If they receive the same chromosome twice= meiosis 2 error
If they receive one of each, just from the same parent= meiosis 1 error
Hardy Weinberg assumptions:
- No mutation
- No natural selection
- Random mating
- No net migration
Occurs during gametogenesis; at a loci where there’s already on allele that is inactivated via methylation and then the solo activate allele gets delete leading to disease
Imprinting
If MATERNAL is deleted= Angelman Syndrome
If PATERNAL is deleted= Prader Willi Syndrome
Hyperphagia, Obesity, Intellectual disability, hypogonadism and hypotonia
Px: “parent must lock cabinets bc the kid just keeps eating!”
Prader Willi Syndrome
Inappropriate laughter, seizures, ataxia, severe intellectual disability
Angelman Syndrome
You share 1/2 of your genes with your siblings; Therefore how many genes are shared with 1st cousins? 2nd cousins?
Times 1/4
1st cousins= 1/8
2nd cousins= 1/32
Fathers transmit to ALL daughters, but no sons
Mothers transmit to 1/2 of daughters or sons
X-linked dominant trait
Examples:
- Hypophosphatemic Rickets
- Fragile X
- Rett Syndrome
- Charcot Marie Tooth Dz
Muscle biopsy shows “ragged red fibers”; pt px with myopathy, lactic acidosis and CNS Dz secondary to failure in oxidative phosphorylation
Mitochondrial myopathies
Ps: Telangiectasia, recurrent epistaxis, skin discolorations, AV malformations, GI bleeding, hematuria
Hereditary hemorrhagic telangiectasia
-Auto dominant
Increase MCHC. Rx with splenectomy.
Hereditary spherocytosis [due to defect in spectrin or ankyrin] leading to hemolytic anemia
I’m a Marfan’s patient, which of my valve will be “floppy”?
Mitral Valve
100% penetrance always BUT variable expression. Px: Cafe au lait spot, cutaneous neurofibromas. Auto Dominant, Chromosome 17
Neurofibromatosis Type 1
Px: Bilateral acoustin schwannomas, juvenile cataracts, meningiomas and epndymomas [Chromesome 22]
Neurofibromatosis Type 2
What deletion is commonly linked to CF?
Phe {phenelyalanine} 508; misfolding leading to retention of protein in RER [channel never makes it to membrane]- defect in CFTR gene on chromosome 7
CFTR encodes: ATP gated Cl- channel that secretes Cl- in lungs and GI tract and reabsorbs Cl- in sweat glands
Clearance of leukocytic debris associated with Cystic fibrosis
Rx: Dornase Alfa [DNAse]
X-linked FRAMESHIFT mutation leading to truncated dystrophin proteinand accelerated muscle breakdown
Onset before age 5 !
Duchenne muscular dystrophy
“weakness begins in pelvic girdle and progresses superiorly” + pseudohypertrophy of calf muscles due to fibroFATTY replacement
+ Gower maneuver [use of UE to help them stand]
COD for kid with Duchenne Muscular dystrophy
Dilated cardiomyopathy
This acts as an anchor for muscle fibers; connection actin to the transmembrane proteins alpha and beta dystroglycan [ECM]
Dystrophin
[loss of dystrophin= myonecrosis] + increases CPK and increase aldolase as seen on Western blot
X linked POINT mutation- w/ later onset of myonecrosis that’s not too too severe
Becker muscular dystrophy
Myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy and arrhythmia caused by a trinucleotide repeat
CTG trinuc repeat in the DMPK gene –> Myotonic Type 1
Px: post pubertal macroorchidism, long face, large jaw, LARGE EVERTED EARS, autism, MITRAL VALVE PROLAPSE
CGG trinucleotide repeat, X-linked
Fragile X Syndrome
Top three causes of Down Syndrome
- Nondisjunction during maternal meiosis 1
- Robertsonian translocation
- Mosaicism [post fertilization mitotic error]
Increase nuchal translucency, hypoplastic nasal bone, increased serum Beta hCG, decreased serum PAPP-A
First trimester labs for Downs Syndrome
*Downs is the only Autosomal trisomy with INCREASED Beta hCG
Decreased AFP and decreased estriol, increased serum Beta hCG, increased inhibin A
Second trimester labs for Downs Syndrome
*Downs is the only Autosomal trisomy with INCREASED Beta hCG
Px: retardation, small jaw, rocker bottom feet, CLENCHED HANDS, low set ears, congenital heart disease
Edwards Syndrome [18]
First trimester labs- EVERYTHING is decreased: PAPP-A, Beta hCG, AFP, estriol, Inhibin A [last one could be normal]
Px: microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease
Patau Syndrome [13]- least common
First trimester labs- The only INCREASE is in nuchal translucency. [everything else decreases]
“Long arms fuse; short arms lose”
Robertsonian Translocation
Px: microcephaly, retardation, HIGH PITCHED CRY/ “MEOWING”, epicanthal folds, cardiac issues [VSD]
Cri-du-chat Syndrome
MOA: Microdeletion of short arm of chromosome 5
“William” has an “elf like” face, he’s retarded, but has well developed verbal skills and is extremely friendly with strangers despite cardiovascular issues and HYPERcalcemia [he’s sensitive to Vit D]. He’s been like this since he was about 7 yo.
microdeletion of LONG ARM of chromosome 7
Williams Syndrome
Cleft palate, Abnormal face, thymic aplasia, cardiac defects, HYPOcalcemia
microdeletion at chromsome 22q11
Px: DiGeorge Syndrome or Velocardiofacial Syndrome
“CATCH 22”
Prevents squamous metaplasia. Used to Rx Measles and AML [M3]
Vit A
Night blindness, dry skin, alopecia, keratomalacia, immune suppression
Vit A Deficiency
Alopecia, Cerebral edema, teratogenic [need pregnancy test]
Vit A Excess
Thiamine Pyrophosphate- Vit B1 [TPP] is a cofactor for which 3 enzymes?
“ATP”
- Alpha ketoglutarate [TCA]
- Transketolase [HMP shunt]
- Pyruvate dehydrogenase [glycolysis to TCA linker]
Impaired glucose breakdown leading to ATP depletion that’s worsened by glucose infusion
Vit B1/Thiamine deficiency
Damage to medial dorsal nucleus of the thalamus and mammillary bodies
Wernicke-Korsakoff Syndrome
Polyneuritis, symmetrical muscle wasting
DRY Beri Beri
high output cardiac failure [dilated cardiomyopathy] + EDEMA
WET Beri Beri
Makes FAD and FMN and is therefore essential to redox reactions/ FAD is a cofactor for Succinate dehydrogenase rxn in the TCA cycle
Vit B2/ riboflavin
Inflammation of lips/scaling and fissures at the corners of the mouth + corneal vascularization
Vit B2 deficiency
“don’t B2 quick to kiss someone without checking the corners of their mouth first!”
Derived from tryptophan. Synthesis requires Vit B2 and B6.
Niacin/ Vit B3
Decreased tryptophan absorption leading to decreased Niacin
Hartnup Dz
Diarrhea, Dementia [Hallucinations], Dermatitis
Pellegra/ Niacin B3 deficiency
Facial flushing [prostaglandin induced], Hyperglycemia & Hyperuricemia
Niacin toxicity
Essential component of Coenzyme A and therefore a cofactor for acyl transfers and fatty acid synhase
Vit B5/ Pantothenate
Cofactor used in: transamination [ast/alt], decarboxylation rxns, glycogen phosphorylase and used to synthesis other vitamins [like Niacin] and several neurotransmitters
Vit B6/ Pyridoxal Phosphate
Cofactor for carboxylation enzymes [Pyruvate carboxylase, Acetyl CoA Carboxylase, Propionyl CoA Carboxylase]
Vit B7 - Biotin
Important for the synthesis of nitrogenous bases in DNA and RNA
Vit B9 - Folic Acid
Macrocytic, megaloblastic anemia with hypersegmented neutrophils but no neurological signs
Vit B9 deficiency
Labs: increased homocysteine, normal methylmalonic acid
+ the person is most likely pregnancy or an alcoholic
Folic Acid/B9 deficiency
Macrocytic, megaloblastic anemic with hypersegmented neutrophils + neuro signs: paresthesias and subacute combined degeneration due to abnormal myelin
Vit B12 deficiency
*The neuro sx are similar to Vit E deficiency sx
Labs: increased serum homocysteine and increased methylmalonic acid
Vit B12 deficiency
Anti-intrinsic factor antibodies
Pernicious anemia
Facilitates iron absorption by reducing it to the Fe2+ state. Necessary for hydroxylation of proline and lysine in collagen synthesis
Vit C
Vitamin necessary for dopamine Beta hydroxylase [conversion of dopamine to NE]
Vit C
Subperiosteal hemorrhages and “corkscrew” hair are linked to
Scurvy/Vit C deficiency
Vit D is exacerbated by:
- Low sun exposure
- Pigmented skin
- Prematurity
This Dz causes increased activation of vitamine D by epitheliod macrophages and therefore labs will show hypercalcemia
Sarcoidosis
Protects Erythrocytes and membranes from free radical damage… that’s this vitamin’s only job!
Actually, it can enhance anticoag effects of Warfarin too…
Vit E
*Vit E deficiency mimicks Freidreich’s ataxia a bit [if it’s severe enough]
Synthesized by intestinal flora and a cofactor for the gamma-carboxylation of glutamic acid residues on various protein required for blood clotting
Vit K
Labs: Neonatal hemorrhage with increased PT and increased aPTT but NORMAL BLEEDING TIME
Vit K deficiency
Vitamine K antagonist
Warfarin
Clotting factors that rely on Vit K for activation
Factors 2, 7, 9, 10, Protein C and Protein S
Delayed wound healing, hypogonadism, decreased expression of “adult” hair patterns [pubic, facial, axillary], anosmia + increased risk for alcoholic cirrhosis
Zinc deficiency
Inhibition of alcohol dehydrogenase. An antidote for methanol and ethylene glycol poisoning
Fomepizole
Inhibition of Acetaldehyde Dehydrogenase causing acetaldehyde to accumulate and contributes to “hangover” symptoms
Disulfiram
The increased liver NADH/NAD+ ratio causes by alcohol leads to:
Lactic acidosis [extra NADH forces pyruvate to lactate]
Inhibition of gluconeogenesis
Fasting hypoglycemia [the extra NADH forces Oxaloacetate to Malate]
Hepatosteatosis [via favored lipogenesis]
Ketoacidosis
Small child with swollen, edematous belly due to protein malnutrition. + Fatty liver due to decrease apolipoprotein synthesis, Anemia and skin lesions
Kwashiorkor
Very small child with muscle wasting, loss of subcutaneous fat and he also may have some edema. What’s the issue?
TOTAL Calorie malnutrition
-Marasmus= MUSCLE wasting
What’s another name for NO [nitric oxide]?
Endothelial derived relaxation factor
Degeneration of both the ascending [dorsal column] and descending [cortico-spinal tract] leading to loss of position/vibration sense + ataxia + spastic paralysis
Vit B12 deficiency
Major COD in patients recovering from a subarachnoid hemorrhage
Vasospasm
Rx: with Nimodipine [calcium channel blocker]
Ptosis + “down and out gaze” in a patient that has normal light and accommodation reflexes
Diabetic CN 3 neuropathy [parasympathetics only affected with COMPRESSION injury… a DM injury is ischemic thereby only affecting somatic nerve + the sympathetics on them]
Biliary tract disease + linked to acholangiocarcinoma
Clonorchis sinensis
Brain cysts + seizures form a tape worm
Taenia Solium [treat the brain cysts with albendazole by reate the intestinal infection part with praziquantel]
Liver [hydatid] cysts
Echinococcus granulosus
Perianal Pruritus/ Scotch Tape Test
Enterobius
Portal HTN, liver/spleen granulomas
Schistosoma
Rx with praziquantel
Vitamin B12 deficiency linked to a tapeworm
Diphyllobothrium latum
Exchange of genes between 2 chromosomes by crossing over within regions of significant base sequence homology
Recombination
When viruses with segmented genomes [like Influenza virus] exchange segments leading to worldwide pandemics
Reassortment
These vaccines induce only HUMORAL immunity and are stable [meaning that never revert to virulence]. Some require booster shots but you CAN give these to immunocompromised pts
Killed Vaccines:
RIP Always
Rabies
Influenza [shot]
Polio [Salk]
HAV Vaccine
These vaccines induce both humoral AND cell mediated immunity immunity
Live attenuated vaccines
“Live! See small yellow chickens get vaccinated with Sabin Polio and MMR! It’s INcredible!”
Small pox Yellow Fever Chicken pox Polio [Sabin] MMR Influenza [INTRANASAL]
Recombinant vaccines
HBV [antigen= HBsAg] and HPV [6,11,16 and 18]
The only ssDNA virus
Parvovirus
[ssDNA, Naked, linear]
The only dsRNA virus
Reovirus
[dsRNA, naked, segmented]
All DNA viruses replicate in the ______, except _____ [this is also the only DNA virus that is NOT icosahedral- it’s complex]
Nucleus, Poxvirus
*Pox virus carries it’s own DNA dependent RNA polymerase so that’s why it doesn’t need the nucleus to replicate
All RNA viruses replicate in the ______, except ______
Cytoplasm, Influenza virus & Retrovirus
Enveloped DNA viruses
HHP
Herpes
Hepadna [*partially ds and circular]
Pox
Naked DNA viruses
3 Ps 1 A
Parvovirus [*ss]
PapillOmavirus [circular]
POLYOMAvirus [circular]
Adenovirus
Herpes 3, 4, & 5=
3= VZV 4= EBV 5= CMV
What is the diagnostic test for Herpes?
Multinucleated giant cells on Tzank smear
Cowdry bodies- “droplet bodies” seen in
HSV
VZV
CMV
Which DNA/ enveloped virus has reverse transcriptase capabilities?
Hepadnavirus [HBV]
Enveloped, dsDNA, circular
Flesh colored pearly DOME that’s painless but has central dimple that has milky fluid in it. Linked to POX VIRUS [enveloped ds DNA virus]
Molluscum Contagiosum
Pharyngitis/Sore throat with fever. Acute Hemorrhagic Cystitis. Pneumonia. Conjunctivitis.
Adenovirus
[Naked, ds DNA, linear]
Aplastic crisis in SCD pt
Parvovirus
[Naked, ssDNA, linear ]
Fifth Dz/ Erythema Infectiosum/ “Slapped cheek” rash in child
Parvovirus
[Naked, ssDNA, linear]
Hydrops fetalis
Parvovirus
[Naked, ssDNA, linear]
HPV 1, 2, 6 and 11
Warts
HPV= [dsDNA, circular, naked]
HPV 16, 18
Cervical Cancer
HPV= [dsDNA, circular, naked]
Progressive multifocal leukoencephalopathy in HIV pt
JC Virus
type of POLYOMAVIRUS
[dsDNA, circular, naked]
Kidney issues in post-transplant patients
BK Virus
“Bad Kidney”
type of POLYOMAVIRUS
[dsDNA, circular, naked]
Positive sense ENVELOPED RNA Viruses
“So I was at a TOGA party drinking a CORONA, I looked back [RETRO] and I’m POSITIVE I saw FLAVOR-FLAV [Flavi] carrying an envelope”
Togavirus
Coronavirus
Retrovirus
Flavivirus
Councilman bodies [eosinophilic liver globules]
Flavivirus [+, enveloped ssRNA]
HCV
Flavivirus
Fever + Jaundice + Black Vomit
Yellow Fever
[Caused by Arbovirus which is a subtype of Flavivirus]
Fever + Joint Pain
Dengue Fever [caused by Arbovirus which is a subtype of Flavivirus]
How does HCV [Flavivirus] turn into HCC?
Chronic inflammation
How does HBV [Hepadnavirus] turn into HCC?
HBV integrates into host genome and acts as oncogene
Fever, POSTAURICULAR LYMPHADENOPATHY, arthralgias, rash
+ “blue berry muffin” rash [sign of extramedullary hematopoiesis]
Rubella
TOGAVIRUS
[enveloped, ssRNA, + sense virus]
HIV: Which gene is linked to the protein that is the capsid protein that encases the RNA and the reverse transcriptase?
GAG gene –> p24 capsid protein
HIV: Which gene is linked to encoding for ALL 3 of the major HIV related enzymes; allowing for dsDNA to integrate into the host even though retrovirus is a ssRNA, +, enveloped virus:
POL gene –> Reverse transcriptase, asparate protease, integrase
HIV: This protein is encoded by the ENV gene. It is able to cross the placenta It’s known as the “docking glycoprotein” because it is the site of attachment to the host CD4+ T cell’s CCR5
gp120
CCR5= for early CD4+ binding and macrophage binding CXCR4= for late CD4+ binding
HIV: This is a transmembrane glycoprotein that’s linked to fusion and entry of the HIV virus.
gp41
HIV: ______ test is used to RULE OUT HIV due to it’s high sensitivity.
ELISA
HIV: _____ test is used to RULE IN HIV [after ELISA is positive] due to it’s high specificity.
Western Blot
Px: Flu like symptoms + sore throat + FEVER over 100 degrees +/- SOB/ common cold like Sx
Corona virus [SARS]
= +, ssRNA, enveloped
Fatal diarrhea in a child
Reovirus
[dsRNA, naked]
Types of Picornaviruses [+ssRNA, naked]
PERCH
Poliovirus
Echovirus
Rhinovirus [the only one that’s not fecal-oral spread- it’s destroyed by stomach acid that’s why you don’t get stomach colds!]
Coxsackievirus
HAV
RNA is translated into 1 large polypeptide that is cleaved by proteases into functional viral proteins
Aseptic Meningitis
Poliovirus, Echovirus or Coxsackievirus [all are picornaviruses]
[+, ssRNA, naked]
Hand, Foot, Mouth Dz. Myocarditis. Pericarditis.
Coxsackiecirus [Picornavirus]
[+ ssRNA, naked]
If a RNA virus is - sense; what must it do?
- sense RNA viruses must transcribe negative strand to positive. Therefore, - sense RNA viruses have to bring their own RNA dependent RNA polymerase or else replication fails
Infantile gastroenteritis. Major cause of day care center diarrhea due to villous destruction with atrophy leading to decreased absorption of sodium and loss of potassium
Rotavirus/ Type of Reovirus
[dsRNA, naked, segmented]
8 segment genome that contain hemagglutin [viral entry] and neuramindase [virus progeny release]. Pts are at risk for bacterial super infection. Virus shows rapid genetic changes.
Influenza virus
[Orthomyxovirus - ssRNA, - sense, segmented, enveloped, linear]
What causes gradual genetic drift leading to epidemics?
Random mutation
Croup/ seal-barking cough
Parainfluenza [Paramyxovirus]
= ssRNA, -sense, enveloped]
Bronchiolitis, Pneumonia in infants.
RSV [Paramyxovirus]
=ssRNA, -sense, enveloped
This protein causes the respiratory epithelial cells to fuse and form multinucleated cells. It is the MOA of the paramyxovirus family [RSV, Measles/Mumps, Parainfluenza/Croup]
F [fusion] protein
Rx: Palivizumab [monoclonal antibody against F protein] prevents pneumonia caused by RSV in premature infants
Koplik spots. Decending rash.
[Cough, Coryza and Conjunctivitis]
Measles [paramyxovirus]
= ssRNA, -sense, enveloped
What is used to prevent severe exfoliative dermatitis in malnourish children [that have measles]?
Vitamin A
Parotitis, Orchitis, Aseptic Meningitis. Possible sterility after puberty.
Mumps [paramyxovirus]
= ssRNA, -sense, enveloped
Bullet shaped virus. Negri bodies in Purkinje cells of the cerebellum and in hippocampus.
Px: Agitation, photophobia, hydrophobia, paralysis, coma –> death.
Rabies virus [Rhabdovirus]
=ssRNA, -sense, enveloped
Hepatitis with high mortality in pregnant women. Fecal oral transmission especially with waterborne epidemics
Hepevirus
= ssRNA, + sense, NAKED virus
+ The vowels hit your bowels… note that both of the fecal oral transmitted/ non-carrier/ non-chronic hepatitis viruses are non-enveloped/naked virus that are + sense, ssRNA
The only marker present during the HBV window period?
Anti HBc IgM [plus Anti HBe]
Serum shows HBsAg, Anti HBe and Anti HBc IgG
Chronic HBV with low infectivity
Serum shows Anti HBs and Anti HBe IgG
HBV Recovery
Serum shows AntiHBs only
HBV Immunized person
Cotton wool spots on fundoscopic exam and may be accompanied by esophagitis. CD4+ count usually below 50.
CMV Retinitis
If HIV patient with superficial vascular proliferation, need to distinguish if there are NEUTROPHILIC INFILTRATES or LYMPHOCYTIC INFILTRATES.
Neutrophili infiltrates denote bacteria infection with ___
Lymphocytic infiltrates denote viral infection with ___
Neutrophilic= Bartonella Henselae [Bacillary angiomatosis]
Lymphocytic= HHV-8= Kaposi sarcoma
Ground glass apperance on imaging. CD 4+ count less than 200. pnuemonia
Pneumonocystis jirovecii
TB-like Dz with CD 4+ counts below 50
Mycobacterium avium
Increased pulse pressure
- Hyperthyroidism
- Aortic regurg
- Arteriosclerosis
- Obstructive sleep apnea
- Exercise
Decreased pulse pressure
- Aortic stenosis
- shock
- tamponade
- heart failure
Stroke volume is affected by:
- Contractility
- Afterload [inverses]
- Preload
If Ejection fraction is decreased in systolic heart failure; how does it change in diastolic heart failure?
EF is NORMAL in diastolic heart failure
Increased SV. Increased EF. Decreased HR.
Digoxin
Blood viscosity depends mostly on…
hematocrit [% of RBCs in the blood]
Resistance is DIRECTLY proportional to viscosity and vessel length but inversely proportional to…
the radius to the 4th power
What would cause the “Venous return” line to shift to the right/ increase?
Fluid infusion
Sympathetic activity
What would cause the “Venous return” line to shift to the left/decrease?
Acute hemorrhage
Spinal anesthesia
What causes an increase in TPR? [meaning that the X- intercept is unchanged by the cross over is below the original?
Vasopressors
What causes an decrease in TPR? [X-int is unchanged by the cross over point is ABOVE the original?
Exercise, AV shunt
Pressure Volume Loop: Extended further left [decreased ESV] and taller
Increased contractility
Pressure Volume Loop: Skinny and tall; halved [increased ESV] but no x-axis increase
Increased afterload [decreased SV, increased ESV]
Ex: Aortic Stenosis
Pressure Volume Loop: Only extended on the right; no height increase
Increased preload/ volume increase only
Ex: Aortic insufficiency
During which phase of the cardiac cycle is the period of highest O2 consumption?
Isovolumetric Contracttion: Period between mitral valve closing and aortic valve opening
What causes a wide split between A2 and P2?
Any delay in RV emptying [regardless of exp vs. insp
- Pulmonic stenosis
- Right bundle branch block
What causes Fixed splitting?
ASD [left to right shunt]= increased RA and RV volumes [regardless of breath]
What causes paradoxical splitting?
Any delay in LV emptying. Will hear P2 before A2.
- Aortic stenosis
- Left Bundle Branch Block
Auscultation: Aortic Area
Only systolic murmurs heard here.
- Aortic stenosis
- Flow murmur
- Aortic valve sclerosis
Auscultation: Pulmonic Area
- Pulmonary stenosis
- Flow murmur
Auscultation: Left sternal border
Systolic:
-Hypertrophic Cardiomyopathy
Diastolic:
- Aortic Regurg
- Pulmonic Regurg
Auscultation: Tricuspid Area
*both of the septal defects are best heard in the tricuspid area
Pan/Holo systolic murmurs:
Tricuspid regurg
VSD
Diastolic:
Tricuspid stenosis
ASD
Auscultation: Mitral Area
Systolic:
-Mitral regurg
Disatolic:
-Mitral stenosis
Increased intensity of right heart sounds
Inspiration
What maneuver will increase the intensity of a mitral valve prolapse murmur?
-Hand grip maneuver to increase systemic vascular resistance [causes later onset of click]
OR
-Rapid Squatting [to increase venous return and increase preload]
What maneuver will DECREASE the intensity of a mitral valve prolapse murmur?
Valsalva [increases abdominal pressure]
*Valsalva actually DECREASES the intensity of most murmurs; so it’s good to pinpoint HYPERTROPHIC CARDIOMYOPATHY [bc it’s the only way that’s increased with this.]
What increases the intensity of an Aortic Stenosis murmur?
Rapid Squatting [decreases hypertrophic murmur]
What murmurs are increased by the hand grip maneuver?
The regurg’s: MR and AR + VSD
Hypertrophic Cardiomyopathy murmur is decreased with which two maneuvers?
Hand Grip & Rapid Squatting
[Hypertrophic murmur is only increased with Valsalva]
Everything is a “systolic murmur” except:
2 Diastolic:
-Aortic Regurg [High pitched, blowing, bounding pulses, head bobbing] - usually from aortic root dilation
-Mitral Stenosis: OPENING SNAP!; [due to abrupt halt in leaflet motion in diastole]; rumbling later diastolic murmur— The decreased interval between S2 and OS correlates with increased severity; intensity is enhanced by Expiration
1 Continuous:
PDA: continuous machine like murmur, loudest at S2. Due to congenital Rubella usually or prematurity. Best heard at left infra-clavicular area
Which murmur is best heard over the APEX?
MVP
Cardiac nodal cells spontaneously depolarize during ____.
Diastole: resulting in automaticity due to “funny current” [responsible for a slow, mixed Na/K inward current]
In the pacemaker action potential curve, which number/phase corresponds to setting the HR?
The slope of Phase 4: If [Na]: slow diastolic depolarization
Fastest cardiac tissue conduction velocity?
Purkinje fibers [Atrial Muscle is second fastest]
Slowest cardiac tissue conduction velocity ?
AV Node [Ventricular Muscle is second slowest]
What does the QT interval represent?
mechanical contraction of the ventricles
Recite the conduction pathway beginning at the SA node
SA node > atria > AV node > common bundle > bundle branches > Purkinje fibers > ventricles
What things can cause a long QT interval thereby predisposing to Torsades de pointes?
Drugs
Decreased potassium
Decreased magnesium
How do we treat Torsades de pointes?
Magnesium
What drugs are linked to Prolonged QT?
Some Risky Meds Can Prolong Q. T
Sotalol [Class 3/ K block] Risperidone [anti-psych] Macrolides [50s protein inhibitor/block translocation] Chloroquine [anti-malaria] Protease inhibitor [-navir/ HIV] Quinidine [class 1a] Thiazides [DCT diuretic]
Romano-Ward syndrome
Congenital prolonged QT Syndrome
Px: Autosomal Dominant, Only cardiac symptoms
Jervell and Lange Nielsen Syndrome
Congenital prolonged QT Syndrome
Px: Autosomal Recessive, Cardiac issues plus SENSORINEURAL DEAFNESS
This syndrome causes the signal to bypass the AV node completely; just has it’s own pathway [bundle of Kent] that goes rt from Atria to ventricle causing delta wave/ pre- excitation and shortened PR interval
Wolff- Parkinson White Syndrome
You’ll see delta wave with Quinidine and Amiodarone [I think?]
No identifiable waves
Ventricular fibrillation
Atrial rate is faster than the ventricular rate. Both Pwaves and QRS waves are present although the P Waves bear no relation to the ORS complexes.
3rd degree heart block
Responsible for the “aldosterone escape” mechanism. Constricts efferent renal arterioles and dilates afferent arterioles via cGMP promoting diuresis.
Causes vasodilation and decreased sodium reabsorption
Atrial natriuretic Peptide [ANP]
like the opposite of Aldosterone
BNP
Used for diagnosing heart failure; released from ventricles in response to increased tension
Very good NPV
Same actions as ANP
Nesiritide
Recombinant form of BNP for Rx of heart failure
Responds ONLY to increased Blood Pressure
Aortic Arch [vagus nerve to solitary nucleus of the medulla]
Responds to ANY CHANGE in Blood pressure
Carotid Sinus [glossopharyngeal nerve to solitary nucleus of the medulla ]
Largest share of systemic cardiac output
LIVER
Highest blood flow per gram of tissue
KIDNEY
If PCWP is greater than LV pressure…
Mitral Stenosis
The lung is unique in that, hypoxic conditions cause…
VASOCONSTRICTION [other organs, hypoxia induces vasodilation]
What causes the edema?: Heart Failure
Increased Capillary pressure
What causes the edema?: Nephrotic Syndrome/ Liver failure
Decreased plasma protein/ decreased oncotic pressure
What causes the edema?: Toxins/Infections/Burns
Increased capillary permeability [increases the Kf constant]
What causes the edema?: Lymphatic Blockage
Increased interstitial fluid colloid osmotic pressure
Early cyanosis/ “blue babies”. Usually require surgery or PDA maintenance
Right to Left shunt:
- Truncus Arteriosus
- Transposition of Great Vessels
- Tricuspid atresia
- Tetralogy of Fallot
- TAPVR
This is caused due to failure of the aorticopulmonary septum to spiral
Transposition of Great Vessels
[can also link to maternal DM]
Early cyanotic “tet” spells paired with RVH
Pulmonary stenosis [from Tetralogy of Fallot] forces right to left flow across VSD
Self Rx with squatting
Late cyanosis/ “blue kids”
Left to right shunts
VSD, ASD, PDA
Late cyanosis. RVH. Finger clubbing. Polycythemia.
Eisenmenger’s Syndrome [from un-corrected left to right shunt: VSD, ASD, PDA]
Coarctation of the aorta is associated with
Bicuspid Aortic valve
HTN in UE, weak-delayed pulses in LOW [Radiofemoral delay] + one other sign that’s too obvious…
Adult type/ postductal coarctation of the aorta
the other sign= rib notching
Main cause of renal stenosis in a young female
Fibromuscular dysplasia [just abnormal thickening of the vessel wall]
Histo: string of beads/ girls wear pearls.
What are xanthomas?
Sign of hyperlipidemia.
Most likely in eyelids or Achilles tendon.
Composed of lipid laden histiocytes in the skin
Hyperplastic Arteriolosclerosis
- Hyperplasia of smooth muscle cells leading to wall thickening
- link to MALIGNANT HTN
- Onion skin appearance on image
LINK TO ACUTE RENAL FAILURE [flea bitten appearance. fibrinoid necrosis with hemorrhage]
Glomerular scarring leading to Chronic renal failure
Link to hyaline arteriolosclerosis
Progression of Atherosclerosis
- Endothelial cell dysfunction
- Macrophage and LDL accumulation in intima
- Foal cell formation
- Fatty streaks
- Smooth muscle cells migration [PDGF and FGF cause this migration]
- The Smooth muscle cells proliferate and deposit extracellular matrix
- Fibrous plaque
- Complex atheroma
Order of occurrence of atherosclerosis
Abdominal aorta > Coronary artery > Popliteal artery > Carotid artery
Pulsatile abdominal mass that grows overtime + flank pain. The pt is a HTN male smoker over 50 yo.
Abdominal aortic aneurysm
[Usually below renal arteries but above bifurcation]
Px: tearing chest pain, radiating to the back+ unequal BP in arms + mediastinal widening
Aortic dissection
Sequelae–> pericardial tamponade, aortic rupture, and death
Coronary artery spasm at rest. Transient ST elevation [triggers: tobacco, cocaine and triptans]- what do we treat this with?
Calcium channel blockers! [Prinzmetal angina]
Chest pain due to ischemic myocardium but no myocyte necrosis; perhaps myocyte swelling though since this is REVERSIBLE damage
Angina
Order of coagulative necrosis events
Pyknosis [condensed chromatin]
Karyorrhexis [nucleus fragments]
Karyolysis [nucleus dissolves]
When is the most likely time of Neutrophil infiltration post-MI and therefore the most likely risk for fibrinous pericarditis?
Day 1-3 post MI
When is the most likely time of Macrophage infiltration post MI and therefore free wall rupture? [leading to papillary muscle rupture and mitral regurg.]
Day 3-7 post MI
Pathologic Q Waves
Evolving or Old transmural infarct
Location of infarct: Leads II, III and aVF [F= Floor]
InFerior Wall [RCA]
Location of infarct: Leads I and aVL
Lateral Wall [LCX]
Location of infarct: Leads V1-V6
Start at septum and go laterally… all are anterior wall of LV [LDA]
Ventricular free wall rupture leads to
Cardiac tamponade
Heart failure, S3, dilated heart, balloon appearance on CXR. SYSTOLIC dysfunction. Eccentric hypertorphy- causes?
Dilated Cardiomyopathy
ABCCCD
Alcohol Beri Beri [Wet] Coxsackie B virus Cocaine Chaga Disease [T. Cruzi] Doxorubicin
S4, systolic murmur, diastolic dysfunction marked by ventricular hypertrophy with septal predominance. Myofibrillar disarray and fibrosis
Hypertrophic Cardiomyopathy
“Sudden death in young athelete”
Autosomal dominant- Beta myosin heavy chain mutation
Linked to Freidrecih ataxia, too
Can cause dilated cardiomyopathy or restrictive cardiomyopathy
Hemochromatosis
Diastolic dysfunction most often caused by sarcoidosis, amyloidosis, post radiation fibrosis and endocardial fibroelastosis
Restrictive Cardiomyopathy
Endomyocardial fibrosis with prominent eosinophilic infiltrate
Loffler Syndrome
Pulmonary edema [transudation of fluid + heart failure cells/macs in lungs]. Orthopnea. Paroxysmal Nocturnal Dyspnea.
Left heart failure
Hepatomegaly/ Nutmeg Liver. Peripheral edema. Jugular Venous Distention [JVD].
Right heart failure
Rx for Acute CHF
LMNOP
Loop dirueretic Morphine Nitrates Oxygen Pressors/ Positioning [don't lay supine!]
Drugs that decreases heart failure mortality
ACE Inhibitors/ ARBS
Beta Blockers
Spironolactone
Acute bacterial endocarditis
Staph Aureus [previously normal valve]
Subacute bacterial endocarditis
Strep Viridans [low virulence compared to staph aureus/ smaller vegetations]- previously sick valve- linked to dental procedures
If there’s endocarditis but the culture is negative…
Coxiella or Bartonella
Tricuspid Valve endocarditis
Usually an IV drug abuser
Staph Aureus
Pseudomonas
Candida
Signs of Bacterial Endocarditis
Fever
Roth spots [retina]
Osler Nodes [ouch-ler nodes on fingers/toes]
Murmur [NEW onset murmur]
Janeway lesions [palms/soles]
ANEMIA
Nail bed hemorrhages/splinters
EMBOLI
Aschoff bodies [granuloma with giant cells], Anitschkow cells [enlarged macropahges with wavy nucleus] + increased ASO titer.
Link to M protein antibodies/ previous PHARYNGITIS GAS infection
Type 2 HSN
Rheumatic Fever
JONES Criteria
For Rheumatic Fever
Joints [Migratory Polyarthritis] O [OH! the heart! Pancarditis- COD= myocarditis] N [ subcutaneous nodules] E [Erythema Marginatum] S [Sydenham Chorea]
+ FEVER + ESR elevation
Sharp pain made worse by inspiration, relieved by sitting up and leaning forward. Friction rub. ST segment elevation. +/- PR depression
Acute pericarditis
Can be Fibrinous [dressler’s autoimmune], Serous [viral], suppurative [bacterial]
Compression of heart by fluid. Causes equal pressure [diastolic] in all four chambers. Beck triad [hypotension, distended neck veins, DISTANT HEART SOUNDS]. Pulsus Paradoxus. Kussmaul sign. ECG shows “electrical alternans”/ swinging heart in fluid
Cardiac Tamponade
Calcification of aortic root and ascending aortic arch leading to tree bark appearance of the aorta
Syphilitic heart disease causes by disruption of the vasa vasorum with consequent atrophy of the vessel wall and dilation of the aorta
“Ball valve” obstruction of the LEFT ATRIUM associated with multiple syncopal episodes
Imaging shows: Scattered cells w/in mucopolysacc stroma and abnormal blood vessels + hemorrhage
Myxoma
Increase in JVP on inspiration [normally should be a decrease] - leading to impaired filling of right ventricle and blood backing up into the veins—> JVD
Kussmaul Sign
Benigh, painful, RED BLUE tumor under fingernails. Arises from modified smooth muscle cells of glomus body
Glomus Tumor
Found in AIDS pts; benign capillary papules caed by Bartonelle Henselae
Bacillary angiomatosis
Blanching vascular tumors:
Hemangiomas
Non-blanching vascular tumors:
Angisarcomas
Kaposi sarcomas
Unilateral headache, jaw claudication, ophthalmic artery occlusion, polymyalgia rheumatica. Increased ESR. Most commonly affects which artery?
Carotid artery [Temporal/ Giant cell arteritis]
“Pulseless disease”- Where yo pulse? [esp weak UE pulses], Fever, night sweats, arthritis, myalgias, skin nodules, ocular issues
Takayasu arteritis
will see: granulomatous thickening/narrowing of the aortic arch with increasesd ESR
String of pearls on imaging. Lungs/ Pulmonary artery spared. Hepatitis B seropositivity. Renal artery involved. Immune complex mediated transmural inflammation of the arterial wall with fibrinoid necrosis
Polyarteritis nodosa
Rx: Steroids or Cyclophosphamide
Fever. Cervical nodes. Conjunctival injection. Strawberry tongue. Red palms and soles. What do you treat this KID with?
Aspirin to prevent MI/clot
Kawasaki disease
c-ANCA is…
anti- proteinase 3
p-ANCA is …
anti- myeloperoxidase
Nose spared. No granulomas. positive p-ANCA.
Microscopic polyangitis
Asthma. Palpable purpura. Peripheral neuropathy [wrist/foot drop]. Granulomas and eosinophilia. Positive p-ANCA. Increased IgE
Churg Straus
Often follows a URI/ increased IgA –> immune complex deposition with mesangium–> glomerular bleeding. Px: palpable purpura on buttocks/legs, arthralgias, GI pain/melena.
Henoch-Schonelin purpura linked to IgA nephropathy [nephritic]
Early splitting of ureteric bud or development of two separate buds
Double ureter
Which kidney is usually taken during living donor transplantation simply because it has a longer renal vein?
LEFT kidney
Most metabolically active portion of the kidney?
Cortex/ proximal tubule consumes most of the ATP
Used to measure plasma volume
radiolabeled albumin
Used to measure extracellular volume
inulin
What part of the glomerular filtration barrier is lost in nephrotic syndrome?
Charge Barrier/ fused basement membrane with herapan sulfate [negative]
Why is inulin used to calculate GFR?
freely filtered, neither absorbed nor secreted
Creatine clearance slightly OVERESTIMATES GFR because…
Creatinine is moderatly secreted by the tubules
PAH is used to measure Effective Renal Plasma Flow [although it underestimates a bit] because…
Nearly all PAH entering the kidney is excreted. It’s both filtered and actively secreted in the proximal tubule.
Normal filtration fraction of kidney
20%
Decreased RPF. Decreased GFR. No change to FF.
Afferent arteriole constriction [But remember that this just make the prox tubule work harder; will reabsorb a greater % of what’s filtered]
Constriction of ureter causes ____ GFR and ____ FF.
Decreased GFR and Decreased FF
How does normal pregnancy impact reabsorption?
Pregnancy decreased reabsorption of glucose and amino acids in the proximal tubule. So normal pregnant women are peeing out a little glucose and amino acids.
Autosomal recessive disorder- deficiency of neutral amino acid transporters in proximal renal tubule cells and on enterocytes [Tryptophan is best example] . Leads to decreased gut absorption and peeing out of amino acids. results in pellagra sx
Hartnup Dz
- Keep in mind; the transporters that are missing are SODIUM dependent
Pattern of osmolarity along the nephron
Starts isotonic [300] – increases in osmolarity [bottom of loop of Henle has highest osmolarity in the absence of ADH] — then as you ascend up the loop of henle the osmolarity decreases again [hypotonic upon ascent and finall around 100 at DCT]
What does the proximal tubule synthesize and secrete that acts as a buffer for secreted H+?
NH3
What is the role of Angiotensin 2 at the proximal tubule?
stimulates Sodium/Hydrogen exchange; increases sodium, water, bicarbonate absorption
What happens at the thin ascending loop of Henle?
active reabsorption of sodium, potassium and chloride
These indirect induce paracellular reabsorption of Magnesium and Calcium through potassium backleak .
This segment is impermeable to water making the urine less concentrated as it ascends
What is PTH’s action on the PROXIMAL TUBULE?
inhibits sodium/Phosphate exchange thereby leading to phosphate excretion
What is PTH’s action on the DCT?
stimulates calcium/sodium exchange thereby leading to calcium reabsorption
What is Aldosterone’s action on the collecting tubule?
Acts at mineralcorticoid receptor. insertion of sodium channel on luminal side
What is ADH’s action on the collecting tubule?
Acts at V2 receptor. Insertion of aquaporin Water channels on luminal side
Juxtaglomerular apparatus
JG cells= modified smooth muscle of afferent arteriole
Macula Densa= NaCl sensor part of the DCT
When do the JG cells secrete renin?
- Low renal blood pressure
- low NaCl delivery to DCT/Macula Densa
- Increased Beta 1 Sympathetic tone {RI RI}
4 things that the kidney secretes:
- EPO [peritubular capillary bed/ interstitial cells]
- 1,25, OH2 Vit D [prox tubule cells have 1 alpha hydroxylase to make active form]
- Renin [JG cells/afferent arteriole]
- Prostaglandins [vasodilates the afferent arteriole to increase RBF]
What shifts Potassium INTO the cell/ Causes hypokalemia?
HYPO-osmolarity
Insulin [increases sodium/potassium ATPase
Alkalosis [want the acid/ H+ out in exchange]
Beta agonist [increases sodium/ potassium ATPase]
U Waves. Flattened T Waves. Muscle weakness. Arrhythmias.
Low Potassium
Tetany. Seizures. QT prolongation.
Low Calcium [or maybe magnesium too?]
Wide QRS. Peaked T Waves. Arrhythmias. Muscle Weakness.
High Potassium
Kidney stones. Bone pain. Abdominal Pain. Anxiety/ delirium.
High Calcium
Decreased DTRs, bradycardia, hypotension, cardiac arrest, hypocalcemia
High Magnesium
Renal stones. Metastatic calcifications. Hypocalcemia.
High Phosphate
Substances that cause Metabolic acidosis with an INCREASED anion gap [greater than 12]
MUDPILES
Methanol
Uremia
DKA
Propylene Glycol Iron or INH Lactic Acidosis Ethylene Glycol Salicylates [later]
If there’s a metabolic acidosis with NORMAL ANION GAP [8-12] this means…
Primary metabolic acidosis; meaning the issue is a loss of bicarbonate [diarrhea or renal tubular acidosis] .. as opposed to compensatory
If the pH is greater than 5.5 then the issue is DISTAL, if it’s less than the issue is proximal or hyperkalemic [as far as tubular acidosis is concerned
Pyuria, no urine casts.
Acute cystitis
Hematuria, no urine casts.
Bladder cancer or kidney stones
Waxy casts in urine
Chronic renal failure
- Waxy casts suggest slow tubular flow
What are hyaline urine casts composed of?
Tomm Horsfall mucoprotein [secreted from tubular Epi cells]
5 Sx of NEPHROTIC Dz
Proteinuria [greater than 3.5 g/day]- frothy urine Microalbuminemia Edema Hyperlipidemia -Lipiduria [Fatty casts] Hypercoaguable State [+ increase infections]
5 Sx of NEPHRITIC Dz
Hematuria HTN Azotemia Oliguria mild proteinuria
Which two Dz are considered overlap between Nephrotic and Nephritic?
Diffuse prolif. glomerulonephritis
Membrano prolif. glomerulonephritis
Effacement of foot process [involving less than 50% of the glomeruli] similar to minimal change disease but in an adult that’s receiving interferon Rx, has HIV or SCD or abuses heroin
Focal segmental glomerulosclerosis
Diffuse capillary and GBM thickening with granular IF and “spike and dome” EM with sub epithelial immune complex deposits . If it’s not idiopathic, what’s it linked to?
Antibody to phospholipase A2 recepto, drugs [Penicillamine] , HBV/HCV, SLE or tumors
Dz= Membranous nephropathy
Child with normal glomeruli; maybe some lipid in the PCT negative IF, effacement of foot processes. Triggered by immune stimulus or recent infection. Excellent response to steroids. Selective loss of which protein?
Albumin
Nephrotic Diseases [5]
Minimal change Dz Focal Segmental glomerulosclerosis Membranous nephropathy Amyloidosis Diabetic Nephropathy
Nephritic Diseases [4]
Acute poststreptococcal Glomerulonephritis
Rapidly progressive Flomeulonephritis
Berge Dz/ IgA Nephropathy
Alport Syndrome
Subendothelial immune complex deposits with tram track appearance due to GBM splitting via mesangium. What viruses are linked?
HBV/HCV
Membrano prolif. Type 1
Intramembranous IC deposits that are super dense. What substance will be really low/ decreased in serum?
Decreased serum C3 levels due to C3 nephritic factor which stabilizes C3 convertase
GBM thickening, Kimmbelstiel Wilson lesion via nonenzymatic glycosylation of GBM leading to increased permeability and thickening. What happens to GFR?
The nonenzymaic glycosylation of efferent arterioles leads to INCREASED GFR and mesangial expansion
Starry star granular appearance. Hypercellular LM. “lumpy bumpy” due to IgG, IgM and C3 deposition along GBM and mesangium. subepithelial IC HUMPS 2 weeks after a GAS infection of pharynx OR skin. What is the presentation?
Periorbital edema, dark urine [cola-colored], HTN
Labs for Acute post strep glomerulonephritis
Increased anti-DNase B titers and decreased complement level
LM and IF show crescent moon shape. What are the crescent made of?
*Fibrin, plasma proteins [C3b], parietal cells, monocytes and *macrophages
Goodpasture’s sndrome- what type of HSN rxn does this represent?
Type 2 HSN- antibody against GBM and alveolar basement membrane- linear IF
Px: hemoptysis and hematuria
Mesangial proliferation. Mesangial IC deposits and IgA based IC deposits. Often presenting a couple days following a URI. Episodic hematuria with RBC casts. What other issues can you expect?
Henock Schonlein purpura:
- purpura on butt/legs
- GI issues- bleed/pain
- Joint paint
Mutation in type 4 collage that leads to thinning and splitting of the GBM. Usually X-linked and incomplete penetrance with variable presentation. BUT what is the classic presentation for this?
“Can’t see. Can’t pee. Can’t hear”
Eye issues. Glomerulonephritis. Deafness.
Severe complications of kidney stones
Hydronephorsis. Pyelonephritis.
Low pH. Ethylene glycol ingestion, Vit C overdose or Crohn disease. Envelope/dumbbell shaped substance in urine.
Calcium oxalate kidney stone
Rx for calcium oxalate stones?
Thiazides or Citrate
Increased urine pH [the only one with increased pH aside from Calcium PHOSPHATE]. Coffin lid shaped substance in urine. Staghorn calculi can form leading to possible UTI. What underlying condition is this linked to?
Ammonium Magnesium Phosphate/ Struvite stones
Linked to infection with urease positive bugs:
- Proteus
- Staph
- Klebsiella
Low ph. Can see on CT scan but not on X-Ray. Substance is rosette shaped in urine. Linked to Gout or Leukemia.
Uric Acid Kidney Stones
Hexagonal. Most commonly seen in “children with staghorn calculi’. Positive Sodium nitroprusside test.
Cystine stone
Clear cell carcinoma of the kidney originates from which cells? And what makes the cells “clear?”
PCT cells and the cells are filled with lipids and carbohydrates.
What gene is associated with Renal Cell Carcinoma?
VHL gene deletion
There is a papillary carcinoma association with the kidney. What is characteristic for this neoplasm?
The epithelial cells face outward.
Associated with MET protooncogene on Chromsome 7
[Normal clear cell RCC is linked to VHL deletion on chromosome 3]
Benign kidney lesion that’s described as a well circumscribed mass with a central scar. Has large eosinophilic cells with abundant mitochondria with NO PERINUCLEAR CLEARING.
Renal oncocytoma
Perinuclear clearing is characteristic of which type of RCC?
Chromophobe Renal cell carcinoma
Contains embryonic glomerular structures. Presents with HUGE tumor with triphasic histology [stromal component, immature tubules and blastemal elements. What kind of mutation is linked to this?
Loss of function mutations of tumor suppressor genes WT1/WT2 on chromosome 11
What Syndrome is WILMS TUMOR linked to?
Beckwith-Wiedmann Syndrome/ WAGR Complex:
Wilms Tumors
Aniridia [linked to PAX 6 gene mutation]
Genitourinary malformation
Retardation
What are the risk factors for developing “painless hematuria with no casts”?
Transitional cell carcinoma.
Risk Factors:
- P SAC
Phenacetin [painkiller + antipyretic]
Smoking
Aniline dyes
Cyclophosphamide
Squamous cell vs. Transitional Cell
SCC of the bladder linked to chronic irritation and transitions through squamous metaplasia/ dysplastic stage before progressing to carcinoma
Linked to Schistosoma haematobium infection, chronic systitis, smoking and chronic kidney stones. Also presents as painless hematuria though.
Suprapubic pain. Dysuria. Frequency. Urgency. But no systemic signs [no fever. no chills] Caused by E. Coli [will show positive for nitrites because it’s GRAM NEGATIVE], urease positive organisms.
Acute infectious cystitis
What virus is randomly linked to hemorrhagic cystitis?
Adenovirus
Sterile pyuria and negative urine culture with similar symptoms and still no systemic signs suggests..
Urethritis by Neisseria gonorrhoeae or Chlamydia
White cell casts in urine. dyruria. fever. What will the CT show?
Striated parenchymal enhancement.
[Dz= Acute pyelonephritis]
Asymmetric corticomedullary scarring, blunted calyx. Tubules can contain eosinophilic casts resembling thyroid tissue. [Thyroidization of kidney]
Chronic pyelonephritis
Symptoms of nephritis a month after taking a drug that acts as a hapten
NSAID induced interstitial nephritis
Symptoms of nephritis 1-2 weeks after taking drug(s) that acts as a hapten
Diuretic, Penicillin, Sulfonamide, Rifampin induced interstitial nephritis
Cortical infarction of both kidney likely due to vasospam and/or DIC. Linked to what conditions?
Obstetric catastrophes like abruptio placentae or septic shock
Maintenance phase of acute tubular necrosis
OLIGURIC. No pain.
lasts 1-3 weeks
Risk of HYPERkalemia
Metbaolic Acidosis
Recovery phase of acute tubular necrosis
POLYURIC. Too much pee
BUN and creatinine levels revert back to normal.
HYPOkalemia
Parts of the nephron most susceptible to ischemic acute tubular necrosis?
Proximal tubule and Thick ascending limb
Sloughing of renal papillae leading to gross hematuria and proteinuria. Associated with..
DACS [this is Renal Papillary necrosis, btw. ]
DM
Acute pyelonephritis
Chronic Acetaminophen/Phenacetin drug use
SCD [and trait]
Urine osmolarity >500
Urine Sodium 20
High specific gravity
Prerenal Azotemia
Urine osmolarity 40
FENa >2%
Serum BUN/CR <15
Intrinsic Renal failure [ATN]
Consequence of renal failure
MAD HUNGER
Metabolic Acidosis
Dyslipidemia [increased triglycerides]
HYPERKalemia
Uremic Syndrome [Anorexia, pericarditis, ASTERIXIS, platelet issues, encephalopathy, decreased memory, itching/ uremic frost]
Na/H2O rention
Growth issues [children]
EPO failure –> anemia
Renal osteodystrophy [unable to hydroxylate Vit D –> secondary hyperparathyroidism]– subperiosteal bone thinning
Bilateral enlarged kidneys. Flank Pain. Hematuria. HTN [increased renin production]. What are associated conditions?
Berry aneurysms [COD]. Mitral valve prolapse. Benign hepatic cysts.
Potter Sequence. Auto recessive condition. Associated with congenital hepatic fibrosis.
AR PKD
Shrunken kidneys. Inability to concentrate urine. Cysts will be located in …
MEDULLA
Lymph node: Follicle
B-Cells/ Cortex
Secondary follicle= active follicle with pale central germinal centers
Lymph node: Paracortex
T Cells
enlarges in viral infection
How do B cells/ T cells enter the lymph node from blood?
HEV; located in the paracortex
Anal canal lymphatic drainage
Above pectinate line= Internal iliac nodes
Below pectinate line= Superficial inguinal nodes
What’s in the marginal zone of the spleen?
APCs and specialized B cells
*So this is where antigen presentation happens. Marginal zone is between the white and red pulp
What’s in the Periarterial lymphatic sheath within the white pulp of the spleen?
T Cells
Splenic dysfunction leads to…
Decreased C3b opsonization and decreased ability of macrophages in the spleen to remove encapsulated bacteria [SHiNE SKiS]
Medulla of thymus has
T Cells and Hassall corpuscles [linked to eosinophils somehow]
Present endogenously synthesized antigens [Like viral stuff] to CD 8+ T Cells…
MHC 1 [HLA A, B, C]
Present exogenously synthesized protein [bacterial proteins, viral capsid proteins] to CD4+ T Cells
MHC 2 [HLA DR, DP, DQ]
Transport of MHC Class 1 to cell surface is mediated via
Beta 2 microglobulin
HLA A3
Hemochromatosis
HLA B27
“PAIR”
Psoriatic Arthritis
Ankylosing Spondylitis
IBD related Arthritis
Reactive Arthritis/ Reiter Syndrome
HLA DQ2/DQ8
Celiac Disease
HLA DR2
Multiple Sclerosis
also, Hay fever, SLE, Goodpasture Syndrome
HLA DR3
DM Type 1
also Graves Dz, SLE
HLA DR4
Rheumatoid Arthritis
DM Type 1
HLA DR5
Pernicious anemia [Vit B12 deficiency]
Hashimoto Thyroiditis
Only lymphocytic members of innate immune system. Uses perforin and granzymes to induce apoptosis of virally infected cells and tumor cells..
Natural killer cells
- works even when there’s no MHC Class 1
link CD16 to NK cell activation
Costimulatory signal
B7 on APC links up with CD28 on Naive T Cell
CD40L on CD4+ cell links up with CD40 on BCell
CD4+ T Cells secretes 4 cytokines that allow it to differentiate into 4 separate types of “T cell”… they are:
IL 12= Th1
IL 4= Th2
TGF B/ IL 6= Th17
TGF B= Treg
Th1 secretes…
IFN-Gamma [activates macs and CTLs]
inhibited by stuff from TH2 [IL 4 and IL 10]
Th2 secretes…
IL 4. IL 5. IL 6. IL 10.
Eosiniophil recruitment. IgE production from B cells
What is the MOA of Granzyme B? [used by CTLs and NK cells]
Granzyme B is a serine protease
Surface markers: CD3. CD4. CD25 [alpha chain of IL 2 receptor] & trascription factor FOX P3
Regulatory T cell: helps maintain specific immune tolerance by suppressing CD4 and CD8 t cell effector functions
Isotype switching is a type of:
Gene rearrangement
Monomer in circulation. Dimer when secreted. Uses trancytosis to travel. Does NOT believe in complement. Released in secretions [saliva. tears. mucus. Colostrum/early breast milk has this antibody in it.
IgA
Monomer on B cells by Pentamer when secreted. Believes in complement but doesn’t cross the placenta [how to distinguish it from another similar antibody]
IgM
Positive/ Upregulated Acute Phase Reactants
- Serum Amyloid A
- C reactive protein [opsonin]
- Ferritin [binds/sequesters Iron]
- Fibrinogen [correlates with ESR]
- Hepcidin [helps ferritin; prevents release of the bound iron]
Negative/ Downregulated Acute Phase Reactants
- Albumin [conserves AA]
- Transferrin [internalized by macrophages to hide ALL of the iron]
These two substances help PREVENT complement activation on SELF cells [like self-RBCs for example]
DAF [Decay activating factor]- CD55
+
C1 esterase inhibitor
C1 Esterase Inhibitor deficiency causes:
Hereditary angioedema [DO NOT GIVE THESE PPL ACE INHIBITORS!]
C3 deficiency puts you at risk for:
Type 3 HSN type rxns
C5-C9 deficiency puts you at risk for:
Recurrent Neisseria bacteremia
What cytokines are linked to FEVER?
IL 1 and IL 6
Chemotactic factors of neutrophils?
LK B4 and IL 8 [Neutrophils arrive early, so the aren’t L8]
Which cytokine’s claim to fame is similar to GM-CSF in that it supports the growth and differentiation of bone marrow stem cells?
IL 3
Class switch to IgE?
IL 4
“E? 4 Me!?”
Oh… IgG too.
Class switch to IgA?
IL 5
“Ayyyyeeeee! We live at 5!”
IFN alpha and B
Secreted by virally infected cells that act to warm the uninfected cells that trouble is a’coming! So when that same viruses goes to try to infect these “primed” cells; RNAase L and Protein kinase degrade host mRNA and inhibition viral protein synthesis. Essentially the primed cells induce apoptosis thereby interrupting viral amplification completely
What is the receptor that EBV uses to attack the B cell?
CD21 receptor on B cell surface
CD 14 cell marker is specific to…
MACROPHAGES
CD 16 and CD 56 cell marker…
NK Cells
Crosslinked Beta region of TCR to the MHC Class 2 on APCs leads to
Massive release of cytokines= Superantigen infection [Strep pyogenes and Staph Aureus]
This is via direct macrophage/ CD14 stimulation- no T-helper cells involved
Patients are given preformed antibody after exposure to which 4 potentially deadly infections?
Tetanus Toxin
Botulinum Toxin
HBV
Rabies virus
“To Be Healed Rapidly”
Delayed response following a TYPE 1 HSN rxn due to:
Leukotrienes [or some other arachidonic acid derivative]
Test for type 1 HSN rxn?
Skin test for specific IgE
Test for type 2 HSN [antibody mediated cytotoxicity linked to macorphages or NK cells] rxn?
direct or indirect Coombs’
What happens in a Type 3 [ Ex: Serum sickness and Arthus reaction] HSN rxn?
Immune complex [Antigen-antibody IgG complex] activates complement which attracts neutrophils and then the neutrophils release lysosomal enzymes
Tes for Type 3 HSN rxn?
Immunoflurescence staining
Tests for Type 4 HSN rxn?
PPD/ Patch Test
What type of HSN rxn is SLE?
Type 3 HSN
Two neuro disorders linked to Type 4 HSN are?
Gullian Barre and Multiple Sclerosis
Anti glutamate decarboxylase antibody
Type 1 DM
Anti Jo-1. Anti SRP. Anti-MI2 antibodies
Polymyositis, Dermatomyositis
Anti-centromere antibody
Limited scleroderma [CREST syndrome]
Anti microsomal and Anti thyroglobulin
Hashimoto Thyroiditis
Anti-Scl 70 [Anti DNA topoisomerase 1] antibody
Diffuse scleroderma
Anti- smooth muscle Antibody
Autoimmune hepatitis
Anti Ro [SSA], Anti La [SSB] Anitbodies
Sjogren Syndrome
IgA antiendomysial, IgA anti tissue transglutaminase
Celiac Disease
Anti-Citrullinated Protein Antibody
Rheumatoid arthritis
Anti UI RNP [Ribonucleoprotein]
Mixed Connective tissue Dz
Infection with GI Giardiasis linked to deficiency of what?
IgA/ B Cell deficiency
What viruses are specifically linked to B cells deficiency even though viruses are usually linked to T Cells?
Enteroviral Encephalitis
Poliovirus [don’t give live
Retained primary teeth. Eczema. Cold abscesses. Low IFN-Gamma
Auto Dom, Hyper IgE Syndrome
DiGeorge 22q11 deletion detected by which method?
FISH
Increased AFP. Decreased IgA, IgG and IgE. Lymphopenia and cerebellar atrophy. Px: Ataxia, Angiomas
Ataxia-Telangiectasia
T cell is unable to reorganize actin cytoskeleton leading to increased IgE and IgA but decrease IgM and IgG + fewer AND smaller platelets
Wiskott Aldrich Syndrome
Giant granules in neutrophils and platelets. Pancytopenia. Coag defects [mild]. Defect in lysosomal trafficking regulator genes leading ot microtubule dysfunction in phagosome-lysosome fusion.
Chediak Higashi Syndrome
Nitroblue tetrazolium dye reduction test will be NEGATIVE
Chronic Granulomatous disease
Defect of NADPH oxidase leading to absent respiratory burst in neutrophils and increased susceptibility to catalase positive organisms [CP SALES]
CGD
Hyperacute Transplant Rejection
Type 2 HSN
Pre-exisiting recipient Abs attach donor antigen and activate complement
Widespread thrombosis of graft vessels/ ischemia/necrosis
Acute Transplant Rejection
CD8+ T Cells activated against donor MHCs OR Recipient antibodies developed after transplant [not preformed]
Leads to vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
Can just give immunosuppressants though [to prevent]
Chronic Transplant Reject
So months to years go by and all of a sudden recipient T cells perceive the donor MHC as it’s own MHC and he thinks that he is being presented antigens. So he reacts against the donor antigen on the donor MHC.
Heart shows- atherosclerosis
Lung shows- Bronchiolitis obliterans
Liver shows- Vanishing bile ducts
Kidney shows- vascular fibrosis or glomerulopathy
Graft vs. Host Dz
T cells from the donor proliferate in the immunocompromised host and reject host cells
Px: rash, jaundice, diarrhea, hepatosplenomegaly.
- Usually occurs in liver and bone marrow transplants [rich in lymphocytes]
- could be beneficial in bone marrow transplant for LEUKEMIA [Graft vs. tumor effect]
The rate limiting enzyme for HMP shunt
Glucose 6 phosphate dehydrogenase [G6PD] - replensishes NADPH
Rate limiting enzyme for de novo pyrimidine synthesis
CPS 2
Rate limiting enzyme for de novo PURINE synthesis
Glutamate PRPP
Rate limiting enzyme for urea cycle
CPS 1
Low malonyl CoA activates this pathway whose rate limiting enzyme is carnitine acyltransferase 1
Fatty Acid Oxidation [mito]
*remember FA synthesis is in cytosol
Rate limiting enzyme for ketogenesis
HMG CoA Synthase
What factors stimulate HMG CoA Reductase thereby promoting cholesterol synthesis?
Insulin and Thyroxine
[Glucagon and Cholesterol inhibit it]
Which enzymes require thymine cofactor?
Transketolase [Ribulose 5-phosphate to Fructose 6 phosphate]
Pyruvate dehydrogenase [ pyruvate to acteyl coA]
alpha ketoglutarate dehydrogenase [alpha ketoglutarate to succinyl coA]
Von Gierke’s
Glucose 6 Phosphate deficiency [build up of glucose 6 phosphate- can’t convert back to glucose]
Fructokinase defciency
Accumulation of Fructose= essential fructosuria [can’t convert to F1P]
Fructose intolerance
Aldolase B deficiency [can’t take F1P and split into DHAP and Glyceraldehyde] - Aldolase B is in the Liver. Aldolase A is in skeletal muscle
*Use of same enzyme both ways [from F 1, 6 bisphosphate to the twosome.
Pyruvate synthesis from PEP [gycolysis]
Pyruvate kinase
PEP synthesis for gluconeogenesis from oxaloacetate
PEP carboxykinase
Pyruvate carboxylase [requires biotin]
Pyruvate to Oxaloacetate
Pyruate dehydrogenase [requies TPP/Thiamine]
Pyruvate to Acetyl Coa [TCA]
Remember that the step from methylmalonyl CoA to replenish succinyl CoA [TCA] required Vit B12 [remember that’s how you distinguished vit b12 deficienct anema from folic acid def anema]… But how’d we get methylmalonyl CoA?
Biotin required for conversion from propionyl CoA [from odd chain fatty acids, brached chain AAs, methionine and threonine
PFK-1- rate limiting step in Glycolysis
F6P to F 1, 6, P in cytosol
The effect of arsenic on ATP production
Completely shuts it down! Causes glycolysis to produce ZERO net ATP
Tetrahydrofolates are activated carriers, what are they carrying?
1 carbon units
SAM is an activated carrier of what?
methyl groups/ CH3
TPP is an activated carrier of what?
Aldehydes
Where is NADPH used?
NADPH is used in anabolic processes [steroid and fatty acid synthesis as a supply of reducing requivalents]
- Respiratory burst
- cyt p450
- glutatione reductase
Glucokinase vs. Hexokinase
Glucokinase= Liver and Beta cells of pancreas, lower affinity for glucose [higher Km], higher Vmax though/ increased capacity, induced by insulin no feedback inhibition by G6p [instead Fructose 6-P inhibits it]
Glucokinase is linked to gene mutation associated with MODY/ diabetes of the young
What is the action of F2,6 BP on glycolysis?
Stimulation
We know that the first step and the rate limiting step of glycolysis require ATP; which steps produce ATP?
Phosphoglycerate kinase [1,3 BPG to 3 PG]
PEP to Pyruvate [Pyruvate kinase]
Fructose BP and PFK 2 are the same enzyme essentially F BP is activated in fasting state via phosphorylation by protein kinase a [glycagon signaled] to promotoe gluconeogenesis. What happens in the fed state?
Insulin decreased cAMP and PKA, leading to decreased phosphorylated FBP and more PFK 2 –> glycolysis bc PFK 2 goes on to promote Fructose 2, 6 bisphosphate which stimulate glycolysis at the rate limiting enzyme [PFK 1]
Pyruvate dehydrogenase complex contains 3 enzymes and requires 5 cofactors:
- Pyrophosphate/ TPP/ B1/Thiamine
- FAD [B2, riboflavin]
- NAD [B3, Niacin]
- CoA [b5, pantothenate]
- Lipoic Acid
Activated by exercise/ high NAD+/NADH ratio, high ADP and high Calcium
Vomiting, Rice Water stools, GARLIC BREATH— what specific biochemical substance is being inhibited?
Lipoic Acid [cofactor for Pyruvate dehydrogenase complex]
Dx: Arsenic poisoning
The only purely ketogenic amino acids
Leucine and lysine
what happens if you have a pyruvate dehydrogenase deficiency and can’t convert pyruvate to Acetyl Coa/ Can’t start TCA?
- build up of pyruvate gets shunted to lactate via LDH and alanine via ALT
What are the electron transport inhibitors?
Inhib Complex 1= Rotenone
Inhib Complex 2= nothing [remember complex 2 is succinate dehydrogenase though
Inhib Complex 3= Antimycin A
InhibComplex 4= Cyanide/ CO
Inhib ATP Synthase= Oligomycin
Uncoupling agents
Increase permeability of membrane causing a decreased poton gradient and increased O2 production so ATP synthesis stops by Electron transport continues producing HEAT
Examples:
Thermogenin/Brown fat
2, 4 Dinitrophenol
Aspirin [why fevers occur with aspirin overdose]
why can’t muscle participate in gluconeogensis?
It lacks glucose 6 phosphatase
The entire HMP shunt occurs…
In the cytoplasm.
Remember NO ATP is used or produced from HMP Shunt. Just produces reducing equiv and also anabolic potential
The oxidative phase is irreversible and rate limiting step is G 6PD
Which random AA is randomly often paired with Glutathione enzymes [GLutathione peroxidase and Glutathione reductase] and is therefore involved in oxidative burst?
Selenium
A protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation
Lactoferrin
Heinz Bodies. Bite cells. Linked to sulfonamides, primaquine, anti-TB drugs [RIPE].the cause is low NADPH in RBCs leading to hemolytic anemia due to poor RBC defense against oxidizing agents.
G6PD Deficiency
Accumulation of Fructose 1-Phosphate leading to a decrease in available phosphates which results in inhibition of glycogenolysis and gluconeogenesis. What are the sign and symptoms?
Negative urine dipstick bc urine dipstick test only checks for glucose. but there will be reducing sugar in teh urine
Sx: hypoglycemia, jaundice, cirrhosis and vomiting after consumption of fruit, juice or honey
Rx: need to lower intake of both fructose and sucrose [glucose + fructose]
Dx: Fructose intolerance- ALdolase B deficiency
Infantile cataracts. Galactose in urine. “Failure to track objects or failure to develop a social smile” in babies.
Hereditary deficiency of galactokinase [Galactose to Galctose 1-P]
Accumulation of galacitol in the lens of the eye + jaundice, hepatomegaly, retardation
Galactosemia/ absence of galactose 1 phosphate uridyltransferase Must excluse galactose AND lactose [galactose + glucose] from diet
Classic galactosemia can lead to _____ sepsis in neonates.
E. Coli
Sorbitol pathway
Glucose to sorbitol [Aldose reductase]
Sorbitol to Fructose [sorbitol dehydrogenase]
Which organs/cells have both aldose reducatse and sorbitol dehydrogenase?
Liver, Ovaries, Seminal vesicles. [need the fructose?]
Which organs/ cells only have also reductase and therefore are subject to sorbitol accumulation in hyperglycemia conditions?
Schwann cells [peripheral neuropathy], retina, kidney and lens.
Basic amino acids/ Positively charged [or NOT CHARGED AT ALL in the case of Histidine] at body pH
Arginine, Lysine, Histidine
*Part of histone to bind negatively charged DNA
What effect does hyperammonemia/excess NH4+ have on the TCA cycle?
Hyperammonemia depletes alpha ketoglutarate leading ot inhibition fo TCA cycle
Tremor. Asterixis, slurred speech, somnolence, vomiting, cerebral edema, blurred vision
Ammonia intoxication
What effect do Benzoate or Phenylbutryrate have on hyperammonemia?
Both bind amino acid and lead to excretion so they can potentially decrease ammonia levels
What is the role of Lactulose in treating hyperammonemia?
Lactulose will acidify the GI tract and trap ammonia for excretion
Increased ornithine with normal urea cycle enzymes suggest:
hereditary N-actylglutamate [cofactor for CPS 1 enzyme] deficiency
Excess Carbomoyl phosphate is converted to orotic acid and you find orotic acid in blood and urine in this condition. Plus lab shows decreased BUM, sx of hyperammonemia but NO MEGALOBLASTIC ANEMIA [which would be a sign of orotic aciduria]
Ornithine transcarbamylase deficiency
Epinephrine synthesis pathway
Phenylalanine to Tyrosine [Tetrobiopeterin] Tyrosin to Dopa [Tetrobiopeterin] Dopa to DOpamine [Vit B6] Dopamine to NE [Vit C] Ne to Epi [SAM]
Tryptophan + B6
Niacin
Tryptophan + BH4/ Tetrahydropberitin (and B6?)
Serotonin
Histidine to Histamine
Vit B6
Glycine to Porphyrin to Heme
Vit B6
Glutamate to Gaba
Vit B6
Arginine to Nitric Oxide
BH4
Albinism. Enzyme defect?
Tyrosinase [Dopa to Melanin]
Decreased phenylalanine hydroxylase or decreased BH4 cofactor leading to seizures, retardation, fair skin, ecezema and musty body odor
or microcephaly, congenital heart defects and growth issues in neonate if maternal
PKU [Tyrosine becomes ESSENTIAL / need from diet]
PKU patients must avoid this in their diet..
Artificial sweetners/ Aspartame [contains phenylalanine]
Phenylketones that show up in urine of a PKU pt
phenylaccetate
phenyllactate
phenylpyruvate
Px: Dark connective tituse. Brown sclera. Urine turn black on prolonged air exposure. debilitatin arthralgiase due to homogentistic acid build up being toxic to cartilage.]
Alkaptonuria/Onchronosis [congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate] Auto recessive
Px: increased homocystein in urine, reatrdation, osteoporososis, tall stature, kyphosis, len subluxation [downward and inward], thrombosis and atherosclerosis [stroke and MI]
Homocystinuria
Homocysteine to Methionine [b12 required]. whats the enzyme?
Homocystein methyltransferase
Homocystine plus serin plus Vit B6 yield what? [the enzyme is Cystathionine synthase]
Cystathionine/ Cysteine
Px: increased alpha ketoacids in the blood [especially leucine], CNS defects, Retardation, death. Urine smells like maple syrup/burnt sugar. Auto recessive. What must be restricted in diet?
Branched amino acids:
Leucine, Isoleucine and Valine
+ need to give thiamine supplement
Phosphorylation of Glycogen phosphorylase via Glycogen phosphorylase kinase leads to…
breakdown of glycogen —> glucose [phosphorylation ACTIVES the breakdown enzyme]
Phosphorylation of GLycogen synthase via Protein kinase A [from glucagon] leads to…
inhibition of glycogen synthase, no glycogen production
Severe hypoglycemia, increased glycogen in liver, increased blood lactate and hepatomegaly. Whats the enzyme defect?
GLucose 6 phosphatase [Von Gierke]
Cardiomyopathy, glycogen build up . Enzyme defect?
Acid maltase/ Lysosomal alpha 1, 4 glucosidase [Pompe]
Hypoglycemia, increased glycogen but NORMAL blood lactate levele
Debranching enzyme defect [alpha 1, 6 glucosidase]- {cori’s Dz]
Increased glycogen in muscle, painful muscle crampl, myoglobinuria /red urin with strenous exercise and arrhthmia
Myophosphorylase/ Skeletal muscle glycogen phosphorylase defect [McArdle’s]
Px: Haptosplenomegaly, pancytopenia, aseptic necrosis of bones + lipid laden macrophages resembling crumpled tissue paper.
Deficient Enzyme: Glucocerebrosidase [accumulation of glucocerebroside]
Gaucher Dz
Px: Progressive neurodegeneration. Cherry red spot on macula, lipid laden macrophage, hepatosplenomegaly
Deficienct Enzyme: Sphingomyelinase [accumulation of spingomyelin]
Nieman Pick Dz
Progressive neurodengereation, cherry red macula, lysosome with ONION SKIN, NO HEPATOSPLENOMEGALY
Deficient Enzyme: Hexoamindase [accumulation of ganglioside]
Tay Sach Dz
Peripheral Neuropathy. Optic atrophy. Globoid cells
Deficienct Enzyme: Galactocerebrosidase
Krabbe Dz
Central AND peripheral demyelination with ATAXIA, dementia
Deficient enzyme: arylsulfatase A leading to accumulation of cerebroside sulfate
GARGOYLISM, airway obstruction, corneal clouding, hepatosplenomegaly
HURLer syndrome [wouldn’t you throw up if you saw a gargoyl?]
Deficient Enzyme: alpha L iduronidase leading to accumulation of heparan sulfat and dermatan sulfate
Mild gargoylism maybe, mild airway obstruction, mild hepatosplenomegaly PLUS Aggressive behavior. No corneal clouding
… no corneal clouding bc Hunter’s need to see clearly to aim at their “X” [this and Gabry’s are X-linked]
Hunter’s Syndrome
Deficient enzyme: Iduronate Sulfatase leading to accumulation of heparan sulfate and dermatan sulfate
Inability to transport Long chain fatty acids into the mitochondria resulting in accumulation causing weakness, hypotonia and hypoketotic hypoglycemia
Carnitine deficiency
Alcoholism causes excess NADH to shunt oxalaoacete to malate leading to a buildup of
Acetyl CoA [thereby shunting glucose and free fatty acaids toward the production fo ketone bodies
In prolonged starvation and DKA, oxaloacetate is depleted for gluconeogenesis leading to a build of
Acetyl CoA [thereby shunting glucose and free fatty acids toward the production of ketone bodies
A urine test for ketones if a person’s breath smells “fruity” finds what?
Acetoacetate only…. Beta hydroxybutryate is NOT detected via urine test
PRoteins and carbs
4 kcal/gram
Fats
9 kcal/gram
Alcohol
7 kcal/gram
HMG Co A Reductase/Cholesterol synthesis is induced by
Insulin
Conversion of HMG CoA to mevalonate
HMG CoA Reductase
Lecithin cholesterol acyltransferase [LCAT], what’s it’s purpose?
Esterification of cholesterol
Found on endothelial surface, this enzyme is responsible for the degradation of TG circulating in chylomicrons and VLDLs.
Lipoprotein Lipase [LPL]
Degradation of TG remaining in IDL
Hepatic TG Lipase
Cofactor for Lipoprotein lipase found in Chylomicron, VLDL and HDL
Apo C 2
Apo B100
Bind LDL receptor [found in VLDL, IDL, LDL]
Mediates chylomicron secretion
Apo B 48 [only in chylomicron and chylomicron remnant]
Mediates activation of LCAT found in Chylomicrion and HDL only]
Apo A-1
Found in everything by LDL, mediates remnant uptake
Apo E
Where do Chylomicron and VLDL get their re-up of Apo C and Apo E from?
HDL
[Alcohol actually increases synthesis of HDL]
Heaptive overproduction of VLDL. Causes pancreatitis and increased blood level of VLDL and TG
Familial dyslipidemia type 4: Hyper TG
Situations where ESR is decreased
SCD [altered shape]
Polycythemia [increased RBCs dilute]
CHF
Main mediators of Cachexia
TNF-Alpha [Cachectin
IFN- Gamma
IL 6
Beta hcG positive tumors
- Hydatifiform moles
- Choriocarcinoma
- Testicular Cancer
Vinyl Chlorida exposure is linked to neoplasm to which organ?
Liver/ Angiosarcoma
Oncogene: BCR/ABL
CML/ALL [tyrosine kinase]
Oncogene: c-myc
Burkitt’s Lymphoma
TS Genes: BRCA1/2
DNA repair proteins
TS Gene: p16
Mealnoma- cyclin depedent kinase inhibitor usually
p53 is
normally the transciption factor for p21/ blocks G1 to S phase transition
Time to steady state concentration depends primarily on:
half life. [it’s independent of dose and dosing frequency]
Drug Rxn: Flushing
VANC
Vancomycin
Adenosine
Niacin
Calcium CHannel Blockers
Coronary vasospasm
Cocaine
Sumatriptan
Drug Rxn: Hyperglycemia
Taking [these] Pills Necessitates Having Blood Checked
Tacrolimus Protease Inhibitors Niacin Hydrochlorothiazides Beta blockers Corticosteroids
Drug Rxn: Hypothyroidism
LAS
Lithium
Amiodarone
Sulfonamides
Drug Rxn: Pseudomembranous Colitis
Clindamycin
Ampicillin
Cephalosporin
Drug Rxn: Agranulocytosis
Dapson Clozapine Carbamazepine Colchicine Methimazole PTU
Drug Rxn: Hemolytic anemia in G6PD Deficiency
“Hemolysis is D PAIN”
INH Sulfonamides Dapsone Primaquine Aspirin Ibuprofen Nitrofurantoin
Drug Rxn: Megaloblastic anemia
Phenytoin
Methotrexate
Sulfa drugs
Drug Rxn: Fat redistribution
PiG
Protease inhibitors
Glucocorticoids
Drug Rxn: Gingival hyperplasia
Phenytoin
Vera[amil
Cyclosporine
Nifedipine
Drug Rxn: Hyperuricemia/ Gout
Painful Tophi? Feet Need Care.
Pyrazinamide Thiazides Furosemid Niacin Cyclosporine
Drug Rxn: Photosensitivity
She SAT For “Photo”
Sulfonamides
Amiodarone
Tetracycline
5-FU
Drug Rxn: Rash/ Stevens Johnsons
Anti seizure drugs, Allopurinol, Sulfa drugs, Penicillin
Drug Rxn: SLE like syndrome
Isoniazid
Hydralizine
Procainamide
Sulfa drugs
Phenytoin
Etanercept [TNF alpha blocker]
Seizure inducing drugs
BUP! II CC [I seiz]
Buproprion Isoniazid if Vit B6 Deficient Imipenem Cilastatin metoCLOpramide [causes tardive dyskinesia too] Tramadol Enflurane
Drug Rxn: SIADH/ Can’t concentrate serum sodium
Carbamazepine, Cyclophosphamide
SSRIs
Drug Rxn: Interstitial nephritis
Methicillin
NSAIDs
Furosemide
Drug Rxn: Drug cough
Amiodarone
Bleomycin/Busulfan
Methotrexate
Sulfa Drugs
FACTSSS + P
Furosemide Acetazolamide Celecoxib Thiazides Sulfonamide Sulfasalazine Sulfonylureas
Probenecid
Cyt p450 Substrates:
[4 As]
Always, Always, Always, ALWAYS Think When Starting Other drugs
Anti seizure Anti depressants Anti psychotics Anesthetics Theophylline Warfarin Statins OCPs
Cyt p450 Inducers:
“Chornic Alcoholic Mona steals Phen-Phen and Never RIF-uses Greasy Carbs”
Chronic Alcohol Modafinil St. John's Wort Phenytoin Phenobarbital Nevirapine Rifampin Griseofulvin Carbamazepine
Cyt p450 Inhibitors:
“Acute alcoholic Gentleman, Cipped Iso-Iced Grapefruit juice QUIckly [while] AMy KEpt Mac’in on Sulfur CInammon RITz
Acute alchol Gemfibrozil Ciprofloxacin Isoniazid Grapefruit Juice Quinidine Amiodarone Ketoconazole Macrolides Sulfonamides Cimetidine RItonavir
Universal PLASMA donor
AB blood group
[ no antibodies in plasma] and no antibodies form in plasma bc he’s got both A and B on RBC surface so that means he can ACCEPT RBCs from anyone because he’s already got both antigens.
Universal RBC donor
O blood group
[ no surface antigens] Since no surface antigens; both A and B antibodies in plasma [ can receive plasma from anyone since he’s already got both antibodies in the plasma and no antigens on his surface anyway]
Basophilic stippling
Lead poisoning
Thalassemias
Anemia of Chronic Dz
Alcoholism
Transfusions: Acute blood loss or severe anemia
Give Packed RBCs to increase Hb and O2
Transfusions: To stop significant bleeding
Give platelets to increase platelet count [in the case of decreased count or quality]
Transfusions: DIC, Warfarn Overdose, TTP/HUS, Cirrhossis
Give Fresh frozen plasma to increase coag factor levels
Transfusions: If Coag factor deficiencies involving fibrinogen and Factor 8
Give cyroprecipitate which contains fibrinogen, factor 8, factor 13, vWF and fibronectin
Labs: Low Iron, Increased TIBC, DECREASED FERRITIN [the only anemia with this], decreased % sasturation
Iron deficiency anemia
Labs: Decreased Iron, Decreased Transferrin or TIBC and Increased Ferriton
Anemia of Chronic Disease
Labs: INCREASED IRON, decreased transferrin/TIBC, increased Ferritin and greatly increased % transferring saturation
Hemochromatosis
What effect does PRegnancy/ OCP use have on Iron?
Increases Transferrin/TIBC and Decreased % transferrin saturation
Px: Microcytic anemia, GI and kidney issues. Mental issue sin kids + headache, memory loss and demyelination in adults. What enzyme is affected?
Ferrochelatase [mito] and ALA dehydratase [Lead Poisoning]
Protoporphyrin and Delta ALA will accumulate in the blood
Px: 5 Ps: Painful abdomen, PORT WINE colored URINE, Polyneuropathy, Psychological issues, Precipitated by drugs, starvation, alcohol, etc. - What enzyme is affected?
Porphobilogen deaminase [Acute intermittent porphyria]
Porphobilinogen, Delta ALA, coporphobilonogen are accumulated in the urine
Px: Blistering cutaneous photosensitivity. Which enzyme is affected?
Uroporphyrinogen decarboxylase [Porphyria cutaneua tarda] — Uroporphyrin / tea colored urine is the key!
Rate limiting step for Heme synthesis
Delta aminolevulinic acid Synthase [issues lead to sideroblastic anemia]
Glucose and Heme inhibit this enzyme
This is why you give Glucose and Heme to treat Acute intermittent porphyria bc you want to inhibit ALA Synthase
CD 15 and CD 30 positive B Cells [Best prognosis if lymphocyte rich]
Reed Sternberg Cells/ Hodgkin Dz
t(8,14) = t(c-myc, heavy chain Ig) + Starry Sky apperance [sheets of lymphocytes with interspersed macrophages. This is associated with which virus?
EBV
Dz: Burkitt Lymphoma
t(14,18) = t(Heavy chain Ig, bcl-2)
Follicular Lymphoma [waxing and waning lymphadenopathy] or Diffuse Large B Cell Lymphoma [most common in adults]
A neoplasm of mature B cells that’s CD5+ and is linked with t(11,14)= t(Cyclin D1, Heavy chain Ig) translocation
Mantle Cell Lymphoma
Px: Cutaneous lesions, lytic bone lesions and hypercalcemia. Associated with HTLV-1 [a retrovirus] and linked to IV drug abuse
Adult T cell Lymphoma
Px: increased susceptibility to infection, Primary amyloidosis of IgG protein, punched ou lytic bone lesions, M Spike, Bence Jones protein [Ig light chains in urine], Rouleauz formation
Multiple myeloma
Make sure you know that the M Spike here is IgG vs. Waldenstrom macroglobulinemia which has an M spike too but it’s IgM
Hyperviscositiy symptoms + NO LYTIC BONE LESIONS + M spike
M spike = IgM= Waldenstrom Macroglobulinemia
t(9,22) = BCR-ABL hydbrid
CML
t(15,17)
M3 type of AML- Rx with all trans retinoic acid
Dendrites in skin
Langerhan cells
Px: lytic bone lesions in a child or recurrent otitis media with a mass involving the mastoid bone. Cells are immature and express S-100 [MESODERMAL ORIGIN] + CD1a marker.
Will see Birbeck granules/ tennis rackets on EM.
Langerhans cell histiocytosis
