Block 8 Flashcards
PD-1 receptor
Programmed death receptor 1 is expressed on the surface of activated T-cells. It binds to its ligand, PD-L1, downregulating the immune response against tumor cells primarily by inhibiting Cytotoxic T-cells. Many types of cancer cells evade the immune system by increasing expression of PD-L1. Monoclonal antibodies against PD-1 have been developed that prevents the binding of PD-1 to PD-L1, this blocks T-cell inhibition, thereby restoring cytotoxic resposne and promoting apoptosis of tumor cells.
- its used in advanced melanoma and types of lung cancer.
Pseudomonas microbiological features
- Motile aerobic gram negative rod
- Non lactose fermenting, oxidase positive
- Produced pyocyanin
- Emits a grapelike fruity odor
- Produced endotoxin (fever, shock) and exotoxin (inactivates EF-2)
Axillary nerve injury
It occurs most commonly in the setting of shoulder trauma(anterior dislocation, proximal humeral fracture).
Patients have sensory loss over the upper lateral arm and weakness on shoulder abduction due to denervation of the deltoid muscle.
Aromatase deficiency
Autsomal recessive disorder that manifests early in embryonal life with high androgen, low estrogen levels in female fetus.
- maternal virilization commonly occurs during pregnancy due to transfer of excess androgen into maternal circulation.
- affected newborn girls have normal internal genitalia and ambiguous or male type external genitalia.
- men with aromatase deficiency have tall stature and osteoporosis but no genital abnormalities.
HIV treatment - anti gp41
Fusion inhibitros – ENFUVIRITIDE
- inhibits HIV fusion with target cell membrane by binding to HIV gp41.
Nephrotic syndrome –> loss of immunoglobulins
Loss of immunoglobulins and low molecular weight component of complement such as factor B make patients with nephrotic syndrome vulnerable to infections especially pneumococcal.
Holoprosencephaly
Embryology: incomplete divison of the forebrain into 2 hemispheres
Etiology: trisomy 13, sonic hedgehog gene mutations, maternal alcohol use.
Clinical features:
mild: closely set eyes (hypotelorism)m clieft lip/palate
Severe: single midline eye (cyclopia), primitive nasal structure, midfacial clefts.
Its an example of “developmental field defect” (also digeorge syndrome) : initial embryonic disturbance leads to multiple malformation by disrupting the development of adjacent tissues and structure within a particular region.
Antibodies reactive with sheep erythrocytes
Hetrophile antibodies- infectious mononucleosis , monospot test
Avascular necrosis(osteonecrosis) causes, clinical, gross and microscopic inspections
Causes:
-thrombotic/embolic occlusion (sickle-cell, desmopressin sickness)
- glucocorticoids
-vascular inflammation/injury
-alcohol abuse
- traumatic fracture
Clinical: pain on weight bearing, decreased range of motion.
Gross: wedged shaped or geographic zones of necrosis, articular cartilages is viable but may be distored or detached from underlting bone
Microscopic: dead bony trabeculae with empty lacunae, necrosis of surrounding adipocytes.
Carotid sinus hypersensitivity
Its triggered by pressure on the carotid sinus by a tight shirt callor.
- the carotid sinus baroreceptros are important in blood pressure control and use arterial wall stretch as an indicator of systemic BP
- the carotid sinus is a dilation of the internal carotid located just above the bifrucation of the common carotid.
- the carotid sinus reflex has an afferent limb : that arised from baroreceptors in the carotid sinus and travels to medullary center via the hering nerve, a branch of glosspharyngeal nerve .
- the efferent limb of carotid sinus, carries parasympathetic impulses via vagus nerve.
Post streptococcal glomerulonephritis , electron microscopy light microscopy
- light: glomeruli enlarged, hyper-cellular.
- immuneflucosrence: granular deposits of IgG, IgM and C3 along basement membrane and in the mesangium (lumpy bumpy appearance )
- electron : electron dense deposits on the epithelial side of basement membrane
Anesthesia in the ischial spine
Is land mark for pudendal nerve block used for anesthesia during vaginal deliveries and for minor surgeries of the vagina and perineum.
Long thoracic nerve injury
Classicaly occurs during axillary lymph node dissection and result in paralysis of the serratus anterior muscle, leading to winging of scapula.
Trapezius weakness symptoms
- Drooping of the shoulder
- Impaired abduction of the arm above horizontal
- Winging of the scapula
- Weakness of sternocleodomastoid may occur if proximal accessory nerve is affected.
- Weakness of arm abduction above horizontal position
Spherical yeast with a thick capsule
Shown on india ink– cryptococus neoformans.
- its present in soil or pigeon droppings .
Psoriasis pathogenesis
- the pathogenesis of psoriasis is complex, involving CD4+ and CD8+, DC and surrounding keratinocytes.
- the interaction among these ,results in production oh TH1 and TH17 type cytokines (including TNF-å,IL-12,IFN-¥,IL-23, and IL-17,) and keratinocytes growth factors –> keratinocytes proliferation, inflammation and angiogenesis.
Bee venom can lead to
Anaphylactic reaction, they contain hyaluronidase, phospholipase and other proteins –> IgE mediated response
NRTI and NNRTI mechanism, HIV Tx
Inhibits HIV DNA synthesis from RNA template by terminating DNA chain allongation.
NRTI: competitive neucleoside /tide RT inhibitor
NNRTI: allosteric RT inhibitor
Axillary nerve - course
- originates from the posterior corrd of the brachial plexus and carries fibers from C5-C6. It courses deep in the axilla below the shoulder joint, then runs through quadrangular space (bounder by superiorly teres minor, laterally humerus, medially lond head of triceps and inferiorly teres major) and along the surgical neck of the posterior humerus. At this point it give rise to motor branches that supply deltoid, and teres minor muscles, and sensory branches that innervates the skin over the lateral shoulder.
Cortisol producing unilateral adrenocortical adenoma can lead to
Unilateral atrophy of the contralateral adrenal gland.
Crigler najjar syndrome I
Autosomal recessive disorder of billirubin metabolism caused by genetic lack of UGT enzyme needed to catalyze bile glucuronidation. When billirubin isn’t correctly enzymatically processed by the liver, unconjugated hyperbillirubinemia develops. Indirect bilirubin levels typically approximate 20-25 mg/dl in these infants, but can rise to as high as 50 mg /dl.
Metabolic pathways involved in pathogenesis of hyperglycemia induced tissue damage
- Advanced glycosylation end products: (AGEs): glucose can nonenzymaitcally attach to proteins and lipids–> reversible glycosylation –> that slowly stabillize into irreversible products.
- under hyperglycemia conditions, AGEs accumulates and facillitate deposition of LDL in blood vessel walls. And inflammatory cell invasion that causes athersclerosis and microangiopathic complications. High glucose in aquous humor –> cataracts. - Polyol pathway overactivity: aldose reductase (glucose –> sorbitol) (which then sorbitol –> fructose). In addition to sorbitol accumulation, aldose reductase consumes NADPH–> depletion –> oxidative stress.
Syringomyelia
- central cystic dilation in the cervical spinal cord enlargs, cuasing damage to ventral white commisure and anterior horns. The ventral white commisure is the site of decussation of the second order lateral spinothalamic tract neurons and the ventral horns are the site of lower motor neuron cell bodies.
- loss of upper extremity pain and tempreture sensation, upper exterimity weakness and hyporeflexoa, lower extermity weaknes and hyperreflexia and kyphoscoliosis.loss of medial laminscus pathway in lower limb (sensation and proprioception), These findings are consistent with syringomyelia.
Spinal accesory nerve , innervates, injury
Its composed of fibers from cranial and cervical nerve roots. Its pure motor nerve that passes through posterior triangle of the neck and provides innervation to sternocleidomastoid and trapezius.
- the trapezius acts to elevate scapula, rotate it upward and stabilize the shoulder.
- the spinal accessory nerve follows a superficial course through the posterior triangle and is vaulnerable to penetrating trauma and iatrogenic injury. (From cervical lymph node dissection).
Antibodies seen in SLE
- ANA: sensitive but not specific
- anti double stranded DNA (anti-dsDNA) antibodies: highly specific for SLE. Only 60% of pts have this (not sensitive)
- Antibodies against small riboneucleotide proteins (anti smith/ anti snRNPs) : 20-30% of patients, also highly specific.
Entacapone mechanism of action
COMT inhibitor that increases the bioavailability of levodopa by inhibiting peripheral methylation. Combining levodopa with entacapone helps increase the plasma half-life of levodopa, producing more stable levodopa plasma concentration and prolonging the therapeutic effect of each dose. COMT inhibitors are used for Parkinson patients with motor fluctuations who are experiencing end of dose wearing off periods with levodopa/carbidopa therapy.
Injury to axillary nerve
Deltoid weakness, impaired abduction of the arm at angles below horizontal plane.
Dubin johnson syndrome
Autsomal recessive disorder charactrized by absence of billiary transport protein, MRP2 (multidrug resistance protein), used in hepatocellular excertion of billirubin into bile caniculi.
The liver is darkly pigmented as a result, but patients typically asymptomatic and suffer no significant side effects.
Sickle cell anemia symptoms
Recurrent episodes of anemia, jaundice and painful swelling of hands and feet.
Antismith antibodies in SLE
- smith protein normally complexes with small nuclear snRNA in the cytoplasm, forming a small nuclear ribonucleoprotein (snRNPs).
- RNA polymerase II synthesizes both mRNA and snRNA, the snRNA combines with specific protein to create snRNP (the target of antismith antibody)
- snRNP and other protein are found in the introns of mRNA and they are removed by spilcosomes.
Glucocorticoids can lead to
- bilateral cortical atrophy of the adrenal gland
- this is due to suppression of ACTH as well as HPA axis suppression.
- sudden cessation of glucocorticoids after prolonged use can lead to adrenocortical insufficiency and adrenal crisis.
Elder abuse
Risk factors: -female, dementia, chronic mental illness , functional impairment, social isolation, shared living envirnoment , poor socioeconomic status
Manifestations:
1. Physical and sexual abuse: atypical abrasion, laceration , fractures, pain not consistent with reported etiologym anogenital injureies, newly acquired STI.
2. Psychological and verbal abuse: changes in behavior and personality, depression, anxiety.
3. Neglect: inadequate nutrition and hydration, pressure ulcers , deterioration of comorbid conditions .
4. Financial exploitation: failure to adhere to medication regiemn, multiple missed appointments, unpaid expenses or rent payments.
Congenital adrenal hyperplasia
- AR
- deficiency in 21 hydroxylase (MCC)
- no aldosterone or cortisol formation
- hypotension
- high ACTH
- increased serum 17-OHprogesterone
- virilization in females
- salt wasting (hyponatremia, hyperkalemia, hypotension, vomiting)
CD28 and CD4 are needed for
T-cell activation.
Renal vein thrombosis: caused by , clinical , pathogenesis
Caused from Nephrotic syndrome - increased glomerular capillary wall permeability in nephrotic syndrome, many important substances are lost in urine, causing number of complications.
- loosing antithrombin III in the urine –> hyper-coagulable state –>RVT develops.
- clinical : sudden onset abdominal or flank pain , gross hematuria , elevated LDH as a result of renal infarction, if left sided –> left varicocele.
Avascular necrosis(osteonecrosis) causes, clinical, gross and microscopic inspections
Causes:
-thrombotic/embolic occlusion (sickle-cell, desmopressin sickness)
- glucocorticoids
-vascular inflammation/injury
-alcohol abuse
- traumatic fracture
Clinical: pain on weight bearing, decreased range of motion.
Gross: wedged shaped or geographic zones of necrosis, articular cartilages is viable but may be distored or detached from underlting bone
Microscopic: dead bony trabeculae with empty lacunae, necrosis of surrounding adipocytes.
Psoriasis treatment
- Topical vitamin D -> calcipotriol, calciterol and tacalcitol.
(These binds to VIT D receptors–> nuclear transcription factor that–> inhibition of keratinocytes proliferation and stimulate differentiation. - Cyclosporine –>it inhibits NFAT –> inhibit T-cell activation
- Enteracept –> recombinant form of TNF. Used to treat moderate to severe plauqe type psoriasis.
- Methotrexate, is thought to target rapidly proliferating epithelial cells in the skin.
5.ustekinumab, monoclonal antibody that targets IL-12, and IL-23 –> inhibits activation of TH1 and TH17
Dorsal scapular nerve
Motor innervation of levator scapulae, and rhomboids
Antibodies that react with the Fc portion of human IgG
Rheumatoid factor is an IgM directed against Fc fragment of self IgG found in patients with RA
Opioid intoxication and opoid receptors:
Mu receptors: physical dependence, euphoria, respiratory and cardiac depression, reduced GI motility, sedation and analgesics.
Kappa: miosis, dysphoria, sedation, analgesia
Delta: antidepressant effect, analgesia( PNS , some opioids)
Naloxone
Pure opoid receptor antagonist devoid of any agonist proporties, used for opoid intoxication or overdose.
- it has the greatest affinity of bindning to mu receptors, and is therfore ideal agent for treating opioid intoxication. As an antagonist it competes with narcotics, displacing them from opioid receptors.
- reversal of effects occurs within minutes.
Digoxin toxicity
Precipitating causes
Cardiac: life-threatining arrythmias
GI: anorexia, nausea. Abdominal pain
Neurological: fatigue, confusion ,weakness ,color vision alterations.
- precipitating causes include: hypokalemia, hypovolemia, and renal failure.
Tx: antidigoxin anti body frgaments
Facial and periorbital edema, mild to moderate hypertension and hematuria suggests
Nephritic syndrome
Conus medullaris syndrome
Lesion at L2, symptoms of flaccid paralysis of the bladder and rectum, impotence, saddle anesthesia.
- there is usually mild weakness of the leg muscles if the lesion spared both lumbar cord and adjacent spinal and lumber nerve roots. Common causes include disk herniation, tumors and spinal fractures.
Femoral ring
Upper opening of the femoral canal, it contains lymphatic vessels and lymph nodes, however, femoral nerve lies laterally to the femoral artery and femoral canal, and its not the femoral sheath,
Association defect
Multiple anomalies without known unifying cause that occur together more frequently than chance alone would predict. (Vertebral defect, anal atresia, cardiac defects , Tracheoesophageal fistal, renal anomalies, and limb abnormalities(VACTERL)
Fibrin deposition in glomeruli
RPGN
Phases of ventricle action potential
Phase 4: resting potential (-90mv)
Phase 0: rapid depolarization : voltage gated Na+ channels open and Na+ rush into cell
Phase 1: initial rapid repolirization, rapid closure of Na+
Phase 2: plateau: opening of L-type dihydropyridine-sensetive Ca++ channels and closure of some of K+ channels. Consequently membrane become highly permable to Ca++ and minimally permable to K+ ions
Phase 3: late rapid repolarization: closure of Ca++ channels and opening of K+ channels. Efflux of K+ from the cell restores the membrane resting potential
IL-5
Secreted by TH2–> stimulating differentiation of B cell and increases IgA production, –> promotes growth and differentiation of eosinophils and is implicated in the pathogenesis of many allergic diseases.
Cauda equina syndrome
- it results from massive rupture of an intervetebral disk that is capable of causing compression of 2 or more of the 18 spinal nerve roots of cauda equina.
- potentially lesion involving S2-S4.
- Lower back pain, radiating to one or both legs, saddle anesthesia, loss of anoccutaneous reflex (pinprick in the perianala area doesnt cause rapid contraction of anal sphincter), bowel and bladder dysfunction(S3-S5), loss of ankle jerk reflex with plantar flexion weakness of the feet.
Anti centromere antibodies
Crest syndrome
Integrase inhibitors
Doultegravir and raltegravir
They inhibit HIV DNA integration into host genome.
Naloxone
Pure opoid receptor antagonist devoid of any agonist proporties, used for opoid intoxication or overdose.
- it has the greatest affinity of bindning to mu receptors, and is therfore ideal agent for treating opioid intoxication. As an antagonist it competes with narcotics, displacing them from opioid receptors.
- reversal of effects occurs within minutes.
chediak higashi syndrome-characterstics
- increased risk of pyogenic infections (deficiency in making phagolysosome) 2. neutropnia due to intramedullary destruction. 3. giant granules in leukocytes 4.albinism and peripheral neuropathy 5. defective hemostasis.
screening for CGD
nitroblue tetrazolium
IL with anti-inflammatory proporties
IL-10 is a cytokine with anti inflammatory properties.IFN-alpha, and TGF-ß also.
Treatment of thymidine kinase deficient Herpes infection
- Commonly present in HIV patients, these are acyclovir resistant strains that lack phosphyrylating enzyme(thymidine kinase)
- these immunocomprimised patients are best treated with foscarnet (pyrophsphate analog viral DNA polymerase inhibitor -doesnt require viral kinase activation) or cidofovir( broad spectrum antivrial neucleotide analogue of cytidine monophosphate, can be converted to active triphosphate without the need of viral kinase).
The optimal site for femoral nerve block is
The inguinal crease at the lateral border or the femoral artery. This also lead to blockage of saphenous nerve to decrease sensation in medial leg below the knee
Independent verification
Its done to prevent wrong site injury, independent verification of the patients, procedure, and site by 2 health care workers, (nurse and physician), should be performed.
Trigiminal neuralgia
Repetitive unilateral shooting pain, in the distribution of CN V that lasts (typically <1 min)
Treated with carbamazepine
delayed seperation of umbilical cord, recurrent infections with no pus
leukocytes adhesion deficiency, also increased circulating neutrophils in the body. its due to defect in integrins (CD18)
Lesch nyhan syndrome
X-linked recessive disorder charactrized by - dystonia, choreoathetosis, self mutilation and hyperuricemia within first few years of life.
- its caused by deficiency of hypoxanthine- guanine phoporibosyltransferase (HGPRT), and enzyme that normally function in purine salvage pathway to convert hypoxanthine back to inosine, monophosphate .
- the absence of HPGRT results in increased degradation of guanine and hypoxanthine –> uric acid, which demands de novo synthesis of purine.
- this leads to increased function in PRPP amidotransferase.
- because purine salvage is defected in lesch-nyhan syndrome, PRPP amidotransferase increase function to supply purine nucleotides.
Cryptococcus infection on brain
- first it infects the lung–>asymptomatic usually
- it has antiphagocytic polysaccharide capsule
- it travels to the brain–> CSF doesn’t contain complement of the alternative pathway –> impaired phagocytosis in CNS.
Bioavilabillity
The fraction of an administered drug that reaches the systemic circulation unchanged. Oral bioavailability is dependent on the intrinsic absorptive properties of the drug as well as any first-pass metabolism that the drug undergoes by enzymes present in intestine or liver.
- a drug that exhibits low concentration in the systemic circulation (low bioavailability = drug that exhibits high first pass metabolism
- other routes of administration are typically employed to bypass portal circulation.
Cluster headache
Untilateral, 15 min- 3hrs duration, repetitive brief headache , excruciating perorbital pain with lacrimation and rhinorrhea. May present with lateral horner syndrome
Acute : treated with sumatriptan, 100% O2
Prophylaxis: verapamil.
Aortic arch reflex is innervated by
Vagus nerve
Amantadine in Parkinson disease
Enhance the effect of endogenous dopamine by increasing dopamine synthesis/release and inhibiting the uptake of dopamine
Opioid intoxication and opoid receptors:
Mu receptors: physical dependence, euphoria, respiratory and cardiac depression, reduced GI motility, sedation and analgesics.
Kappa: miosis, dysphoria, sedation, analgesia
Delta: antidepressant effect, analgesia( PNS , some opioids)
Acute epiglottitis
Occur in children due to hemophilus infleuenza type B (occurs mainly in unvaccinated children)
-epiglottis is seen as cherry-red ,swolen
Difference between viral and bacterial
Viral: MCC - enterococci, arbevirus, HSV-2
CSF: WBC counts <500 cells/mm3, lymphocytes predominance
Glucose levels are normal or slightly reduced.
Protein generally <150 mg/dl
CSF gram stain: no organism
Bacterial: adults : S.pneumoniae, and N.meningitids
Neonates: s.agalactiea and gram negative bacilli.
WBC count in CSF often >1000cells/mm3 with neutrophils predominance.
Glucose levels <45 mg/dl and proteins >250 mg/dl
Often positive for specific organism.
