Block 7 Flashcards
Kinesin
Microtubule associated protein whose function is anterograde transport of intracellular vesicles and organelles toward the plus (rapidly growing) ends of the microtubules.
- in neurons kinesin carries vesicles and organelles away from the cell body and toward the nerve terminal.
- toxic insult to it would be expected to impair anterograde transport resulting in deficiency of synaptic vesicles at the nerve terminal.
Development of kidney
- Development of metanephrons or true kidney begins with metanephric diverticulum formation (ureteric bud), which sprouts off the caudal portion of mesonephric duct
- ureteric bud –> indue formation of metanephric mesoderm (blastema).
- ureteric bud —> give rise to collecting system, collecting tubules, and duct, major and minor calyces, renal pelvis, and ureters.
- metanephric blastema give rise to glomeruli, bowmans space, proximal tubule, loop of henle, and distal convulated tubules
Meningioma
Common, slow growing , benign , tends to arise at regions of dural reflection (falx cerberi, tentorium).
- pts are often asymptomatic but may present with headache, seziures, or focal neurological deficits depending on tumor size and location.
- if occurs in parietal lobe( non-dominant) can cause hemi-neglect synrome as well as sensory loss in lower limb (homoncolus see pic)
Postherpetic neuralgia,
After weeks to months of recovery from shingles, may occur –> it may last several months or longer and has burning stabbing or gnawing character.
Its usually managed with TCA or anticonvulsants, but non systemic options for PHN include lidocaine patches or topical capsaicin.
Antiphagocytic capsule is present in
- S.pneumoniae
- Hemophilus infleunza
- Neiserria
Myocardial cells increase in size in MI
-myocytes switch from aerobic to anearobic –> low intracellular ATP –> ADP,AMP and adnosine acuumulates –> NA/K ATPase and sarcoplasmic reticulum Ca+2 fails, –> increased intracellular Na+ and Ca+2 –> attracts free water –> cellular and mitochondrial swelling
Femoral hernia
Protrude through the femoral ring which can widen and become lax with age. They are lateral to the pubic tubercle and lacunar ligament and medial to femoral artery and vein.
-becuase femoral canal is small they are prone to incarceration
Sotalol
Is class III anti arrhythmic drug with beta blockers properties and used primarily to treat atrial and ventricular arrhythmia
Chanceroid is
Caused by heamophilus ducreyi
Gram negative bacteria transmitted through sexual contact. Present as one or more deep painful ulcers.
With ragged borders –> grey exudates and inguinal lymphadenopathy.
- uncommon in usa more common in sahran african, latin america, regions of asia.
Penta-peptide molecule that acts on mu and delta
ß-endorphins
Hypervariable pilli are present in (bacteria)
N.gonorrheae and N.meningitidis
Ankle ligaments
Medial : anterior tibiotalar, posterior tibiotalr, tibionavicular and tibiocalcaneal
Lateral: calcaneofibular, posterior talofibular, anterior talofibular
Malignant hypertension
Extreme or rapidly developing hypertension .. causes fibrinoid necrosis and hyperplastic arteriosclerosis.
Hyper plastic arteriosclerosis consists of onion like, concenteric thickining of the walls of arterioles due to laminated layers of SMCs with intervening basment membrane reduplication.
Loss of substance in substantia nigra
Parkinson disease
Lewy body presence
Parkinsonism
Capsaicin -drug
It causes buildup of calcium that results in long lasting dysfunction of nociceptive nerve fiberss –> defunctionaliztion.
It causes release and subsequent depletion of substance P, which involved in pain signals.
At first it causes burning, stinging and erythema, but persistent exposure leads to moderate reduction in pain.
Aortic dissection
- severe chest pain
- caused primarily by hypertension and on CT its seen as septum inside the aorta which in fact the tunica intima of the aorta.
DRESS syndrome definition and associations
- usually occurs after starting a medication
- life-threatining conidition that occur 2-8 weeks after drug exposure
- associated with : anticonvulsant (phenytoin,carbamazaepine ) , allupurinol, sulfonamides , and antibiotics (minocycline and vancomycin).
CF patients vs normal epithelium
Nasal transepithelial potential difference test
In intestinal and respiratory epithelium, CFTR channels secretes chloride ions into the lumen and also has a tonic inhibitory effect on the opening of epithelial sodium channel. (ENaC)which decrease sodium reabsorption into the cell.
- this high luminal salt content helps retain water in the lumen forming well hydrated mucus.
- in CF patients, the nasal transepithelia potential differnce test, a saline solution is applied to the nose. Bcz pts of CF have increased sodium absorption via ENaC, Na+ is absorbed intracellulary but chloride in the saline solution is retained in the lumen. –> this will result in more negative transepithelial voltage difference –> due to the high relative amount of chloride on epithelial surface.
Ataxia telengectasia is
- Autosomal recessive disorder, cerbellar atrophy leads to ataxia that occurs in the first years of life (oculocutaneous telangectasia, usually delayed).
- patients with ataxia- telangectasia also have severe immundeficiency with repeated sinopulmonary infections. The risk of cancer in these patients is increased significantly because of inefficient DNA repair.
Glassy material in subenothelial space that stains pink with PAS stain
Characteristic for hyaline arteriosclerosis. Typically seen in the kidney in patients with poorly controled hypertension or diabetes mellitus (glucosylation)
Cysticecrosis
T.solium infection - brain infection with seizures and neurological symptoms
Glaucoma diagnostic features and clinical
- atrophy of optic nerve head.
- more common in advanced ages
- diagnostic :
1. increasd IOP
2. abnormal visual field testing with decreased peripheral vision.
3. Increased cup to disc ratio due to loss in ganglion cell exons.
Hematuria and polycythemia are present in _____ cancer
RCC
Water in mucus on CF patients
Decreased –> resulting in dehydrated mucus that predispose to the formation of mucus plugs and chronic sinopulmonary infections.
Screening for gestational diabetes is best in
3rd trimester
Fungal infection in HIV patients is a result of
- T-cell lymphocytes deficiency –> local candida infection, PCP, cryptococcus
- granulocytes deficiency (neutrophils) –> systemic candida infection, aspergillus and mucor
- B-cell deficiency : giardia (no IgA)
Edwards syndrome features (6)
1.Fetal growth retardation,
2.hypertonia,
3,micrognathia and
4.congeintal heart defects.
5.Clenched hands with overlapping fingers
6.meckles diverticulum and malrotation .
Transduction
Bacteriophage transfers DNA from one bacterial cell to the other.
- while replicating within host bacterium, bacteriophage can accidentally incorporate host bacterial DNA into the phage particle. Once released it can transfer DNA from previous host to newly infected bacterium .
- by this mechanism bacetria can acquire genes for virulence
Trophyrma whippelii characteristics ,treatment-
- actinomycete, rare systemic illness involves small intestine, joints and CNS. They proliferate within the macrophages of these tissues, provoking no inflammatory response as a consequence.
- classic histological findings include small intestine mucosa containing enlarged foamy macrophages packed with both rod shaped bacilli and PAS positive diastase resistnt granules.
- clinically presents with malabsorption, weight loss and diarrhea, arthropathy and playarthritis, and psychatric and cardiac abnormalities observed.
- antibiotic is the treatment
Dilated cardiomyopathy
- (viral-due to inflammation)myocardial inflammation leads to dilation and elarment of the heart chambers -> eccentric hypertrophy –> decreased ventricular contractility –> systolic dysfunction.
- other causes may include genetics, toxicity, pregnancy (peripartum) and hemochromatosis.
- clinical signs pulmonary edema, distended jugular vein , dilated ventricles, pitting edema,
Substance P
Transmission of pain in the CNS
Infected undercooked pork
T. Solium
If it contain only larval cyst –> teaniasis (tapworm infestation)
If it contains eggs –> cysticercosis .
Transformation (bacterial genetics)
Allows the bacterium, to take up exogenous DNA fragments, integrate the DNA into the genome and express,the encoded proteins. Through this method nonvirulent, strains of bacteria that dont form a capsule can acquire the genes that code for the capsule and therefore gain virulence.
Atrophy of caudate nucleus
Huntington disease
SCC of skin- increased risk
- actinic keratoses which are small, scaly, erythmtous lesions with sand paper texture occuring on sunexposed areas.
- hyperkeratosis and parakeratosis and atypical keratinocytes all associated with increased risk for SCC of skin.
- Actinic keratoses dont invade the dermis and are considered to be premalignant lesion.
Steroid and thyroid hormones intracellular pathway
- binding of activated receptor to DNA to modify transcription.
- they bind to intracellular receptors, once these receptors are activated they subsequently bind to promoter region of target genes to modify tanscription.
Opioid receptors
Delta, mu, kappa N/OFQ
Patau syndrome : features
- Cutis aplasia
- Polydactyly
- Cardiac defects
- Renal defects
- Cleft palate, cleft lip
- Umbilical hernia and omphalocele
- Microcephaly/ holoprosencephaly
- Micropthalmia
- Rocker bottom feet
Heparin mechanism of action
See pic
Hypogammagloboulinemia predispose to
Bacterial infections
Patient who is taking phenytoin for seziures, comes with seziures, what drug have she taken that resulted in this
CP450 inducers –> reduce the quantity of phenytoin in the body.
PAS stain is used in
- glyocgen storage disease
- whipple disease (trophyrma whippli)
- long standing D.M or Hypertension – > it stains hyaline which is present in those diseases
Neurocysticercosis
- Taenia solium (pork tapeworm eggs) excerted in feces of human carriers.(T.solium is rare in us but common guatemala and in central and south america ,especially in rural areas)
- clinical: common in central and south america, sub-saharan africa, asia, prolonged incubation months to years , and present with seziures, focal neurological symptoms and intracranial hypertension.(CSF obstruction)
- diagnosed by CT and MRI, eosionophilia and increased ESR
- management: ALBENDAZOLE
Simple diffusion VS protein carrier transport through cell membrane
Simple diffusion is faster
CFTR mutation on bicarbonate
Can lower the rate of HCO3- secretion in pancreatinc duct -> mucin precipitation and formation of intraductal concretion that cause exocrine pancreatic insuffeciency
Endogendous opoids
Enkephalins, endorphins and dynorphins.
These endogenous opoids are released in response to noxious stimuli and binds to different opioid receptors to allow modulation of pain.
-those receptors being mu, delta, kappa, and N/OFQ receptors. Available narcotics like morphine acts on mu receptors and modulating pain preception.
-beta-enodphins is one of the endogenous opioid, its dervied from POMC which produces also ACTH and MSH.
Aqueous humor flow
Produced by cilliary epithelium > posterior eye chamber > transferred through pupil to anterior eye chamber > iridocorneal angle contains trabecular meshwork > diffusion into schlemms canal (scleral venous sinus) >episcleral vein
Sturge weber syndrome
Encephalotrigeminal angiomatosis is a rare neurocutaneous disorder charactrized by the presence of cutaneous facial angiomas as well as leptomeningeal angiomas.
Skin involvment typically overlies V1 and V2.
Its associated with mental retardation, seziures, hemiplegia, skull radiopacities. (Tram-track calcification0
Ibutilide
Class III anti arrhythmic drug used for acute termination of atrial flutter and atrial fibrillation
Mannitol acts on
Descending limb of henle loop and proximal tubule, its an osmotic diuretic that dilute urine.
Intracellular polyphosphate granules are present in (bacteria)
C.diphtheriae. Granules are evident with methylene blue staining
ß-blockers in AMI
- used in AMI to reduce HR,CO,and O2 demands.
- contraindication to ß-blockers are bradycardia, hypotension, overt heart failure (Pulmonary edema).
- non selective ß-blockers can cause bronchospasm in COPD patients (propronalol, nadolol)
- selective ß1 (metoprolol,atenolol, bisoprolol) and combined alpha and beta receptor blockers (carvidelol, labetelol) are well tolerated in COPD patients.
Romberg test tests
Proprioception. Used to distiguish sensory from cerbellar ataxia.
To diffeentiate sensory from cerbellar ataxia–> the patient is asked to close his eyes while maintaining aforementioned posture. Removing the visual input forces patient to rely on input from proprioceptive receptors –>failure to maintain posture when eyes are closed is referred as positive –> sensory ataxia–> defects in posterior coulmn or peripheral nerves (tabes dorsalis or Vitamin B12 deficiency ).
-patients that shows negative romberg are likely to have cerbellar ataxia.
IgG binding outer membrane protein present in
S.aureus . Protein A virulence factor. Protein A binds the FC protion of IgG molecule thereby preventing opsonization, phagocytosis and complement activation.
Factor Xa inhibtors
direct: 1. Apixaban 2. Rivaroxaban Indirect : 1. Fondaparinux
Microangiopathic hemolytic anemia - > caused by drugs
Cancer chemotherapy ( cisplastin and cyclophosphamide)
Spironolactone vs eplerenone
Eplerenone - more specific receptor antagonist with fewer side effects
Von recklinghausens disease
NF-1, neurofibromas, optic nerve glioma, lisch nodules and cafe au lait spots.
Pompe disease
Normal glucose levels with severe cardiomegaly
Glycogen accumulation in lysosomes
Deficient enzyme is lysosomal acid å-1,4- glucosidase with 1,6 glucosidase activity.
Progressive onset of heart failure in the setting of recent viral infection –>
Dilated cardiomyopathy
Molecules that uses JAK-STAT
- GH
- Cytokines (eg. IFN) and
- Hematopoietic GRF (erythropoietin, G-CSF)
Systolic anterior motion of mitral valve is seen in –>
Hypertrophic obstructive cardiomyopathy
Ankle sprains
Lateral ankle ligaments are weaker and are injured more often.
The most common ankle sprain involves the anterior talofibular ligament and present with ecchymosis and pain and anterlateral aspect of the ankle.
Osteoblastic , mixed and osteolytic cancer
Osteoblastic : 1. Prostate cancer 2. Small lung cancer 3. Hodgkin lymphoma Mixed: GI and breast Ostolytic: 1. Multiple myeloma, 2. Non-small cell lung cancer 3. Non-hodgkin lymphoma 4. RCC 5. Melanoma
Gluconeogenesis steps
- Pyruvate to oxalacetate by pyruvate carboxylase
- Oxaloacetate to malate by malate dehydrogenase
- Malate shuttle (exit from mitochondria)
- Malate –> oxaloacetate
- oxaloacetate –> PEP by PEP carboxykinase
- F1,6 Bis –> fructose 6 phsphate (by F1,6 bisphosphatase)
- Fructose 6 phosphate –> glucose (glucose 6 phosphatase)
Cori disease
- debranching enzyme deficiency
- hepatomegaly
- ketotic hypoglycemia
- hypotonia and weakness
- abnormal glycogen with very short outer chains
DRESS syndrome clinical
patient develops fever, generalized lymphadenopathy and facial edema and diffuse morbilliform skin rash that can progress to confluent erythema with follicular accentuation.
Other organs like :
Liver -> hepatomegaly,jaundice
Kidney ->acute interstitial nephritis
Lung -> cough, dyspnea
- laboratory shows eosinophilia , atypical lymphocytosis and elevated ALAT
Von hippel- lindau disease
Rare autosomal dominant condition, characterized by presence of capillary hemangioblastomas, in retina/and or cerebellum as well as congenital cyst or neoplasm in kidney liver or pancreas. (Increased risk for RCC as well)
Insulin resistance in 3rd trimester
Due to HPL. : actions :
- Due to increase –> lipolysis increase –> free FA and ketones providing energy to mother and preserving glucose and amino acids for fets –> in case of malnutrition –> fetus energy from ketone.
- its stimulate pancreatic ß-cells insulin production
What is released from Sacroplasmic reticulum
Ca+2.
Ach release from motor neuron opens post-synaptic ligand gated ion channels –> depolarization of the muscle cell–> depolarization then –> releases Ca+2 from sarcoplasmic reticulum.
Timolol in glaucoma , mechanism
It decreases production of aqueous humor by acting on cilliary epithelium.
Direct thrombin inhibitors drugs (#_
- Argobatran
- Dabigatran
- Bivalirudin
MCardle disease , pathogenesis, clinical , treatment
- its caused by deficiency of myphophorylase, an isoenzyme of glycogen phophorylaze in muscles tissues.
- Deficiency of this enzyme leads to decreased breakdown of glycogen during exercise. –> poor excecise tolerance, muscle cramps and rhabdomyolysis.
- prognosis is generally good and symptoms can be improved by consuming simple sugar before activity.
GH mechanism of action
GH promotes growth by:
- IGF-1 production –> in the liver.
- one GH molecule binds 2 receptors on cell surface leading to activation of Janus kinase (JAK), a nonreceptor tyrosine kinase.
- JAK –> phophorylates tyrosine residues –> docking sites for STAT.
- once STAT is recruited it get phosphorylated by JAK–> induces IGF-1 transcription –> binding to promoter region.
Troponin
Smal globular proteins situated alongside the tropomyosin molecules. Its composed of 3 subunits, troponic I,T,and C.
- troponin T binds the other troponin components to tropomyosin, toponin I binds toponin-tropomyosin complex to actin, and troponin C contains the binding site for Ca+2.
- Ca+2 is secreted from sacroplasmic reticulum, when Ca+2 binds troponin C, tropomyosin shift to expose the actin binding sites for myosin allowing contraction to occur.
DNA repair enzymes deficiency disorders (5)
- Ataxia telangectasia: DNA hypersensetivity to ionizing radiation
- Xeroderma pigmentosum, DNA is hypersensetive to UV radiation, causing premature skin aging and increased risk of skin cancer (malignant melanoma and SCC)
- Fanconi anemia is caused by hypersensitivity of DNA to cross linking agents.
- Bloom syndrome: chromosomal instability. Increased susceptibility to neoplasm is present.
- Hereditary non-polyposis colorectal cancer (occurs due to defect in DNA mismatch repair enzymes. –> susceptibility to colon caner
Regional wall motion abnormality may indicate
MI (ischemic heart disease), contraction is impaired in the damaged myocardium.
Calmodulin and myosin light chain kinase are elements of
the contractile mechanism in smooth muscles (not skeletal)
Which bacteria can undergo transformation
Hemophilus, streptococcus, bacillus and Neisseria species
Patau syndrome genetics:
A defect in the fusion of the prechordal mesoderm an integreal embryological structure affecting growth of face,eyes and forebrain.
-cytogenetic studies usually demonstrate meiotic nondisjunction, nondisjunction leads to fetus with 3 copies of chromosome 13 .
Glyocgenolysis in fasting can hold glucose levels up to
12-18 hrs then gluconeogenesis come to the picture
Neurofibrillary tangles are seen in
Alzheimer disease
Tuberous sclerosis
Hamartomas in kidney,cns,liver,pancreas.
AD disorder
Characterized by cortical and subependymal hamartomas, cutaneous angiofibroma, visceral cysts. Renal angiomyolipomas and cardiac rhabdomyomas. (Clinically, sezuires most concerning)
Achlasia is
Motility disorder caused by reduced numbers of inhibitory ganglion cells in the esophageal wall, which creates an imbalance favoring excitatory ganglion cells.
- manometry shows decreased amplitude of perstalisis in mid esophagus and increased tone and incomplete relaxation at the LES.
- dysphagia, regurgitation and chest pain are common.
- bird beaks sign
Left ventricle wall rupture
It may occur 5-14 days after MI, abrupt rupture leads to hemoperricardium and cardiac tamponade. Patients have suddent onset of chest pain and profound hypotension and shock, with rapid progression to pulseless activity and death.
Open angle Glaucoma drugs mechanism
- Decrease production of aqueous humor :beta blockers , Alpha 2 agnoist and carbonic anhydrase inhibitors
- Increase uveroscleral outflow: prostaglandins agonists
- Increase Trabecular meshwork outflow : muscarinic agonists
Screening for CF
Increase immune reactive trypsinogen
