STEP 1 Week 1 Flashcards
Four impairments in glycogenolysis
Characteristics of Pompe disease and cause
Cause: deficiency of acid alpha glucosidase
Normal glucose levels
Extreme cardiomegaly
Glycogen accumulation in lysosomes
Muscle pierced for chest tube at 5th intercostal space, mid-axillary line
Serratus anterior
Pierre Robin Sequence
Progression of cells after MI
Regulatory T-Cell function
What is the IPEX disorder
Mutation in FOXP3 expression, leads to unrelgulated T and B cell activity
IPEX - Immune dysregulation, polyendocrinopathy, enteropathy, X-linked
See: autoimmune neteritis (villous atrophy,etc), excematous dermatitis, type 1 diabetes in infant
Trigylceride metabolism to glucose
Best long-term therapy for specific phobia
exposure-based CBT
Ovarian venous drainage
Left ovarian vein into left renal vein
Right ovarian vein into IVC
Distribution of data on a bell curve (percentiles)
When is B-HCG detectable in serum and urine
β-hCG is produced by the syncytiotrophoblast after implantation, which generally occurs 6-7 days after fertilization at the earliest. β-hCG typically is detectable in the maternal serum approximately 8 days after fertilization, whereas it is detectable in the urine 14 days after fertilization. Therefore, a serum pregnancy test will be positive before a urine pregnancy test.
What is hyperacute transplant rejection
Occurs minutes to hours
Preformed recipient antibodies against graft antigens
See: mottling and cyanosis, fibrinoid necrosis and capillary thrombotic occlusion
What is acute transplant rejection
Usually <6 months
Donor antigens induces activation of naive immune cells - Cell mediated, sensitization of recipient T cells
See: lymphocytic infiltrate, cd4 deposition, neutrophils, necrotizing vasculitis
What is chronic transplant rejection
Months to years later
Chronic low-grade immune response refractory to immune repression, mixed-cell and humoral
See: vascular wall thickening, interstitial fibrosis, parenchymal atrophy
Process of tRNA amino acid binding
The 3’ CCA tail of tRNA serves as the amino acid binding site.Aminoacyl tRNA synthetase is the enzyme responsible for “loading” the appropriate amino acid to the 3’ terminal hydroxyl group of the CCA tail.
How can buprenoprhine precipitate withdrawals
It is a partial opiod receptor agonist that binds with high affinity but low activity. It can displace other opioids leading to withdrawal
Effects of unilateral renal artery stenosis
Location and effect of adrenergic receptors
What does staph secrete that allows Haemophillus to grow on blood agar
V Factor (NAD+)
Also helps release factor X (hemetin), both are necessary for haemophilus
Pathophys of an acute hemolytic transfusion reaction
Type II hypersensitivty
IgG and IgM autoantibodies with complement activation (cell lysis)
What are clavulinic acid, subactam, and tazobactam
beta-lactamase inhibitors
Most common cause of nosocomial blood stream infections
Intravascular catheters (allows staph to enter bloodstream)
What type of cells allow growth of HPV
Stratified squamous epithelium
Cervix, anus, true vocal cords
Manifestations of hypovolemia
Pathophys of rheumatoid arthritis
Activation of CD4+ T (Th1, Th17) cells and macrophasges secrete IL-1 and TNF-alpha, leading to articular destruction
IL-1 : induces matrix metalloproteinases and T cell response
TNF-alpha: inflammatory cells
Both activate osteoclasts
Causes of nonvalvular heart failure and changes in wall thickness and function
Effects on heart of volume overload vs pressure overload
Volume overload : eccentric hypertrophy (decompensated heart failure)
Pressure overload: Concentric hypertrophy (hypertensive heart disease)
What nerve is impacted in Bell’s palsy
facial nerve (CN VII)
Functions of facial nerve (CN VII)
Motor output to the muscles controlling movement of the face (including eye closure)
Somatic sensation afferents from portions of the pinna and external auditory canal
Special sensation afferents for taste from the anterior two-thirds of the tongue
Parasympathetic innervation of the submandibular and lacrimal glands
Motor innervation of the stapedius muscle, which causes sound dampening
Changes to the lungs with age (lung capacity, FVC, RV)
Lung capacity is unchanged - chest compliance goes down (stiff ribs) and lung compliance goes up (loss of recoil)
FVC goes down (RV bigger portion of TLC)
RV goes up
Sources of nitrogens in purines
Sources of carbon in purines
Ribavirin MOA
Inhibits IMP dehydrogenase, blocks conevrsion of IMP to GMP
Mycophenolate MOA
Immunosuppresant
Blocks IMP dehydrogenase
6-mercaptopurine MOA
What is Lesch-Nyhan syndrome
X-linked absence of HGPRT (cant do purine salvage)
See excess uric acid production (juvenile gout), excess de novo purine synthesis (high PRPP, IMP)
SX: hypotonia, chorea, self-mutilation
Carbon and nitrogen sources for pyrimidines
What is orotic aciduria
Autosomal recessive defect in UMP synthase
SX: orotic acid in urine, megaloblastic anemia, hypersegmented neutrophils
TX: Uridine
Signs of orithine transcarbamylase deficiency
Causes a breakdown in urea cycle
See: increased carbamoyl phosphate and orotic acid in urine, but also see increase in ammonia
MOA of 5-FluroUracil
5-FU is a chemotherapy agent
Mimics uracil. Blocks thymidilate synthase and formation of dTMP
MOA of methotrexate
Blocks dihydropholate reductase so cant form THF, leads to blocked formation of dTMP
B12 vs Folate deficiency
Features of bulemia nervosa
What are the universal stop codons
UAA, UAG, UGA
Lead to releasing factor
Complete vs partial mole
Afferent vs efferent nerves for visual light reflex
Afferent: CN II
Efferent: CN III (edinger westphal for other eye, PNS)
Clinical features of selective IgA deficiency
MOA of carbon monoxide poisoning
CO binds to heme iron with a much higher affinity than oxygen, creates carboxyhemoglobin.
Impedes oxygen delivery and decreases cardiac output
What is type II error
Probability of concluding no difference exists when one actually does exist
What is Power
1 - Type II error
Clinical features of PCOS
Pathophys of PCOS
Increased activity of activity of 17α-hydroxylase; 17,20 lyase; and 3β-hydroxysteroid dehydrogenase. The overexpression of these enzymes results in elevated androgen levels (eg, testosterone, androstenedione, DHEA) and the clinical consequences of hirsutism and acne.
Incresed risk for endometrial carcinoma
Pharyngeal and aortic arches derivatives (1-6)
Changes to glomerular filtration during pregnancy
Because blood volume and cardiac output goes up, GFR increases
Placental proteins also increae permeability of glomerular basement membrane, so see proteinuria
Source of single brain abscess vs multiple
Single - direct invasion from contiguous source
Multiple - hematogenous spread from distant infection
Exudative vs transudative pleural effusions
Regulation of glycogenolysis in liver vs muscle
In liver, regulated by glucagon and Epi through cAMP.
In muscle, regulated by muscle contraction (Ca2+) mostly and some cAMP
Characteristics of drugs that are mainly excreted by the liver
High lipophilicity
High volume of distribution
What is the drawback of using creatinine to measure GFR
Creatinine is secreted by the proximal tubules so the calculated GFR is 10-20% higher than actual GFR
Contents of superior occular vs inferior occular fissures vs optic canal
Features of TCA overdose
Most deaths come from cardiac arrhythmias and refractory hypotension
TX: Sodium Bicarbonate
Pathophys of rheumatic fever
Autoimmune reaction following GAS infection. Antibodies against strep M protein and N-acteyl-beta-D-glucosamine cross react
Infection in children marked by URI sx, stridor, brassy cough, barking cough, hoarsness, resp distress
Laryngotracheitis (croup)
caused by parainfluenza virus - paramyxovirus
Difference between GLUT 1, 2, and 4 transporters
Features of pyruvate kinase deficiency
Converts phosphoenylpyruvate to pyruvate
Sources of fuel over course of 24 hour fast
What is Von Gierke’s Disease (Glycogen storage disease type 1)
Glucose-6-phosphatase deficiency
Sever hypoglycemia between meals, lethargy, seizures, lactic acidosis (Cori cycle)
Enlarged liver (cant get glycogen out)
What is Pompe’s disease (glycogen storage disease II)
Acid alpha-glucosidase deficiency
Accumulation of ghlycogen inside lysosomes
Presents in childhood, severe
See enlarged muscles (cardiomegaly, macroglosia), hypotonia, no metabolic problems but have heart failure
What is Cori’s disease (glycogen storage disease type III)
Debranching enzyme deficiency
Similar to Von Girkes but mild hypoglycemia and have muscle involvement
See enlarged liver and also hypotonia
What is McArdle’s Disease (Glycogen storage disease V)
Glycogen phosphorylase deficiency
Adolescence or early adulthood
No liver problems, but have exercise problems - weakness and cramps
Myoglobinuria and urine turns dark after exercise
Uses of NADPH
What is respiratory burst
Killing of bacteria by phagocytes with oxygen
What is chronic granulomatous disease and features
How is fructose brought into glycolysis
What is essential fructosuria
Deficiency of fructokinase
Benign, fructose not taken up into liver, spills into urine
What is hereditary fructose intolerance
Deficiency in aldolase B
Get buildup up of fructose 1- phosphate and get depletion of ATP
See hypoglycemia, vomiting, hepatomegaly, FTT after weaning off breastmilk
How is galactose converted to glucose
What is classic galactosemia
Deficiency in galactose 1-phosphate uridyltransferase (GALT)
Galactose 1-phosphate builds up in liver and galactose is also converted to galactitol (accumulates in eye like sorbitol)
See hepatomegaly, jaundice, childhood cataracts
Have to avoid milk
Required cofactors for pyruvate dehydrogenase
NAD+
FAD+
CoEnzyme A
Thiamine
Lipoic Acid
What is the malate shuttle
Oxaloacete and NADH cannot cross membrane, but malate can. Malate is used to bring electrons in for NADH and then can be converted into oxaloacete inside mitochondria
How many ATP made per NADH/FADH2
3 per NADH
2 per FADH2
Inhibitors of electron transport chain
What tissues cannot use fatty acids for energy
RBCs (glycolysis only, no mitochondria)
Brain (glucose and ketones only)
What is the carnitine shuttle
Helps fatty acids undergo B-oxidation by moving fatty acyl coA into the mitochondria
Features of carnitine deficiency
Cant bring long chain fatty acids into mitochondria to break down fatty acids
What is a MCAD deficiency
Deficiency in medium chain Acyl-CoA dehydrogenase
AcetylCoA is low so gluconeogenesis is shut down
Pathophys of lactic acidosis in alcoholism
Genetic risk factors for Alzheimers
- Amyloid precursor protein on chromosome 21
- Presinilin 1 on chromosome. 14
- Presinilin 2 on chromosome 1
- ApoE4
Features of cystic fibrosis
Syphillis diagnostic serology
MOA of penicillins
Structurally simialr to D-alanine-D-alanine, bind to transpeptidase that inhibits formation of bacterial peptidoglycan cell way
Mechanisms of septic organ dysfunction (3)
Poor oxygen use
- Bacterial products trigger free radicals that lead to mitochondrial damage = decreased oxydative phosphorylation and lactic acidosis
- Vasodilation shunts blood quickly through organs
- Increased capillary permeability causes edema that increases distance O2 must travel to mitochondria
Deposition seen in poststrep glomerulonephritis
Starry sky (granular) deposition of IgG, IgM, and C3 immune complexes
Stages of alcohol withdrawal
What is integrin
Helps bind cells to one another by binding to fibronectin, collagen, and laminin
What is X-linked agammaglobulinemia
X-linked agammaglobulinemia is characterized by low or absent circulating mature B cells (ie, CD19+, CD20+, CD21+ cells) and pan-hypogammaglobulinemia (low IgG, IgM, IgA). Affected patients have increased susceptibility to pyogenic bacteria, enteroviruses, and Giardia lamblia due to the absence of opsonizing and neutralizing antibodies.
Sources of ATP during exercise (3 phases)
- Phosphocreatine shuttle
- Glycolysis
- Oxidative phosphorylation
Steps of insulin release (start with glucose receptor)
- Glucose enters cell through GLUT-2, broken down by TCA cycle into ATP
- ATP binds K+ channel and closes it, leading to depolarization
- Calcium channel opens
- Insulin release
Permeability of nephron regions to water
What is purulent pericarditis and most common causes
Structures derived from neural crest cells
SOME SALT
Schwann cells, odontoblasts, melanocytes, enterochromaffin cells, spinal membranes [pia and arachnoid], adrenal medulla/ganglia, laryngeal cartilage, tracheal cartilage
Visual pathway
Important HIV genes
Pol gene - encodes protease, reverse transcriptase, integrase
Env gene - surface glycoprotein, enables host immune escape
Nef gene - downregulates MHC 1 on infected cells
Major virulence factor of staph epidermis
Ability to produce biofilm - extracellular polysaccharide matrix
Hormonal control of pancreatic secretions
Prolonged exposure to loud noises causes hearing loss due to damage to the_____ of the ______.
Prolonged exposure to loud noises causes hearing loss due to damage to the stereociliated hair cells of the organ of Corti.
Higher frequency sounds are heard at the ____ of the cochlea
Earlier portion
Low frequency - farther in (cochlear cupula)
Risks and protective factors for epithelial ovarian cancer
The pathogenesis of epithelial ovarian cancer is linked to the frequency of trauma and repair at the ovarian surface. Oral contraceptives, multiparity, and breastfeeding are protective by decreasing the frequency of ovulation. Risk factors include BRCA mutation, nulliparity, and infertility.
What causes diastolic heart failure
Hypertension, obesity, infiltrative disorders (transythyretin-amyloid, sarcoidosis)
Caused by decreased LV compliance, see normal LVEF. and LV end-disatolic volume, but high LV filling pressures
Portions of hypothalamic nuclei that mediate food intake
Venteromedial. - mediate satiety, destruction = hyperohagia
Lateral - mediates hunger, destruction = anorexia
Portions of. hypothalamic nuclei that mediate heat
Anterior. - heat dissipation, destruction = hyperthermia
Posterior - heat conservation, destruction = hypothermia
Gram stain of common infectious urethritis organisms
N. Gonorrhea - Gram negative, see intracellulat diplococci
Chlamydia trachomatous and mycolplasma - do not graim stain because not enough peptidoglycan
Radial nerve function and sensory distribution
Function of Natural Killer cells
Recognize and kill cells with reduced MHC 1 expression (virus, tumor). Contain perforins and granzymes that lead to apoptosis
What is the alanine cycle
During starvation, alanine in muscles is transported to the liver. In the liver alanine is converted into pyruvate which can. be used to generate glucose
What is the Cori cycle
Muscle and RBC convert glucose to lactate which then goes to the liver. Lactate can then be converted to glucose to. be sent back to the muscle
Kwashiorkor vs Marasmus
Kwashiorkor is inadequate protein intake, see edema (low albumin)
Marasmus is insufficient calories, no edema
Hypoglycemia causes when after feeding vs fasting
After feeding: Galactosemia, hereditary fructose intolerance
Fasting: Glycogen storage disease
Sypmtoms of proprionic aciduria and methylmalonic aciduria
Poor feeding, hypotonia, vomiting, lethargy
Metabolic acidosis (anion gap)
Hypoglycemia and ketosis
Hyperammonemia, elevated organic acids in serum/urine
What is maple syrup urine disease
Branched chain amino acid disorder - deficiency of alpha ketoacid dehydrogenase
Get buildup of branched change AA and alpha ketoacids
Branched chain amino acids
Leucine, isoleucine, valine
Two causes of hypoketotic hypoglycemia and features
Carnitine deficiency - low carnitine levels, low acyl-carnitine levels
MCAD deficiency - High acylcarnitine. level and highicarboxylic acids
Features of ornithine transcarbamylase deficiency
High ammonia
High orotic acid
Hallmark of mitochodnrial disorder
High alanine
Pyruvate cannot be converted to. acetyl coA. (usually by. pyruvate dehydrogenase in mitochondria) so converted to alanine
Cell type and function
Cause and effect of midgut malrotation
Rotation of 180 instead of 270 degrees counterclockwise
Results in cecum in RUQ - intestinal obstruction due to bands connecting to mesentary over duodenum.
Can also get twisting around superior mesenteric artery
Lymph drainage of rectum
Above dentate line - internal illiac and inferior mesenteric, some superior mesenteric
Below dentate line - inguinal nodes
The live attenuated oral (sabin) polio vaccine creates a stronger ____ response than the inactivated (salk)
IgA - made in duodenal lumen
Contact dermititis, granulomatous inflamation, and reactive skin testing are all forms of ____
Type IV hypersensitivity - T cell mediated
Causes of eccentric vs concentric LV hypertrophy
Concentric - pressure overload
Eccentric - volume overload
How can cancer cells. mutate to resist anti-cancer drugs
The human multidrug resistance (MDR1) gene codes for P-glycoprotein, a transmembrane ATP-dependent efflux pump protein that has a broad specificity for hydrophobic compounds. This protein can both reduce the influx of drugs into the cytosol and can increase efflux from the cytosol, thereby preventing the action of chemotherapeutic agents.
EKG leads
Mechanical dysfunctions associated with MI timeframe and SX
Anion gap equation
Na+ - (Cl- + bicarb)
Normal: 10-14
Cause of an non-anion gap met acidosis
Loss of bicarb
Diarrhea, renal tubular acidosis, saline infusion
What muscles are targeted in pelvic floor strengthening
Levator ani
pubococcygeus, puborectablis, illeococcygeos
Difference between DNA replication in eukaryotes and prokaryotes
- Prokaryotes have 5 DNA polymerases, eukaryotes have 3
- Eukaryotic is much larger genome
- Prokaryotic is circular and has one cite of replication. Eukaryotic is linear with multiple cites (faster)
Portosystemic anastamoses
Low dose aspirin mechanism and side effects
COX-1 inhibition, risk of gastric bleeding
Pathophys of myasthenia gravis
Autoimmune disease that leads to dicrease in number of acetylcholine receptors, reduces the amplitude of the motor end plate potential
Hemodynamic changes seen in aortic regurgitation
Will result in eccentric hypertrophy so larger LV
Causes an overall increase in systolic bp due to increase cardiac output and contractility
Aortic diastolic will be low and LV diastolic will be high
MOA of acetominophen toxicity
Formation of NAPQI that disrupts hepatocyte mitochondrial function and causes hepatic oxidative damage
Abortive and preventative therapy for migraines
Pathogenesis of primary aldosteronism
Techniques for motivational interviewing
OARS
Open ended questions, affirmations, reflect, summarize
Portion of hypothalamic nuclei involved in circadian rhythyms
suprachiasmatic
Symptoms of parvovirus B19
Symptomatic anemia, decreased erythropoesis, transient aplastic crisis. Worse in patients with hemoglobin disorders
See giant pronormoblasts and intranuclear inclusions
Features of the Phenylalanine hydroxylase reaction
Hydroxylation of phenylalanine is irreversible so phenylalanine cannot be derived from tyrosine.
Phenylalanine hydroxylase uses the co-enzyme tetrahydrobiopterin (BH4) to supply reducing equivalents for the hydroxylation reaction.
Over the course of the phenylalanine hydroxylase reaction tetrahydrobiopterin is oxidized to dihydrobiopterin.
Tetrahydrobiopterin is regenerated from dihydrobiopterin by dihydrobiopterin reductase in a reaction involving the oxidation of NADPH.
What is hartnup disease
Autosomal recessive Absence of an AA transporter in the proximal tubule
Leads to loss of tryptophan in the urine, can cause niacin deficiency that lead to sx (pellagra)
What is the alanine cycle
Use of alanine to transfer ammonia to the liver
Drugs that can cause a folate deficiency
Phenytoin
Methotrexate
Trimethoprim
What is the hallmark of a B12 deficiency
Hugh methymalonic acid
Neuropathy (legs>arms)
What is pernicious anemai
Autoimmune destruction of gastric parietal cells (type 2 hsr) that leads to deficiency of intrinsic factor so low B12
Associated with. HLA-DR and gastric adenocarcinoma
What vitamin allows for conversion. of Fe3+ to Fe2+
Vitamin C
Improtant for Heme synthesis and collagen synthesis
Vitamin high in sarcoidosis
Vitamin D
Conversion to 1,25 hydroxyvitamin D independent of the kidney, so get high calcium
What is acrodermatitis enteropathica
Low Zinc
Dermatitis, decreased hair, diarrhea, poor growth
What is Lecithin-cholesterol acyl transferase (LCAT)
Catakyzes rdterification of cholesterol - packages it tightly in core of HDL
Activated by A-1 on HDL
What is the most common cause of community-acquired pneumonia and describe vaccine
Strep pneumoniae (Gram negative)
Two vaccines:
- Pneumococcal polysaccaride vaccine, 23 valent, moderate B cell response
- Pneumococcal conjugate vaccine, polysaccride conjugated to protein so get robust T cell response
Mechanism of cataracts
Nuclear sclerosis (layers), photooxidative damage to crystalline, osmotic damage
Gene and associations
Features of carcinoid syndrome
What types of cells are involved in superantigen. response
T- cells (IL-2)
Macrophages (IL-1)
MOA of opioid side effects
Direct activation. of mast cells - release of histamines
Conduct disorder vs Oppositional defiant disorder
Conduct disorder is more severe, includes aggressive behavior, stealing, destruction
Oppositional defiant disorder is less severe, more irritable mood and defiance
What type of collagen is found in scars?
Type I
Type I vs Type II muscle fibers
Symptoms of cauda equina syndrome
Sciatic nerve - back. pain, lower limb weakness
Pudendal nerve - saddle parasthesia
Pelvic splanchnic (PNS) - constipation and urinary retention
Risk factors and sx of anal squamous cell carcinoma
What are the retroperitoneal organs
SAD PUCKER
Impact of hyperthyroidism on SVR
Increased metabolic demand and direct effect of thyroid hormone on vascular smooth muscle leads to vasodilation and decreased SVR
What is a septic abortion and common organisms
Infected retained products of conception
Staph. aureus
E. coli and group B strep
Steps of insulin synthesis and secretion
Most common side effects if Amphotericin B
Renal toxicity - can get hypokalemia and hypomagensemia
Normocytic anemia
What is heparin induced thrombocytopenia (HIT)
IgG antibodies against heparin and platelet factor IV, induces platelet aggregation
TX: Direct thrombin inhibitor (hirudin, lepirudin, argatroban)
Fetal vs adult hemoglobin
Fetal hemoglobin is made up of 2 alpha and two delta subunits, and has a hgher affinity for oxygen (allowd for better delivery of oxgen to baby)
Adult hemoglobin is two alpha and two beta. Replaces fetal by 6 months
Clinical manifestations of hemochromatosis
What glucose transporter is responsive to insulin and where is it located
GLUT 4
Adipocytes and skeletal muscle
Common DNA damage cuased by UV radiation
Pyrimidine dimers
What is the cause of microsatellite instability
Deficiency of mismatch repair (DNA slippage that is not repaired)
Cause and SX of ataxia telangectasia
Deficiency in non-homologous end joining repair
How are herpes virus antivirals activated
Drugs for HSV and VZV are phorpylated twice, first by viral thymidine kinase
Drugs for EBV and CMV are only phosphorylated by human TK because those viruses wont phosphorylaye
What is adenosine deaminase
Enzyme in purine metabolism that converts adenosine to inosine. Without it, toxic metabolites are made that inhibit DNA and lead to apoptosis.
ADA deficiency is bad for highly dividing cells like lymphocytes (severe combined immunodeficiency)
Action potentials of pacemaker vs non-pacemaker cells
TCAs side effects
Coma
Cardio stuff
Confusion
Anticholinergics
Causes of cleft lip amnd cleft palate
Cleft lip- maxillary prominence fails to fuse with intermaxillary. segment
Cleft palata - Palantine shelves fail to fuse with each other or with the primary palate
Caused by polygenetics and environment
Causes of polyhydramnios
What causes hemosiderin laden macrophages in the lungs
Chronic passive lung congestion as a result of chronic heart failure - fluid backs up in the lungs and RBC are pushed into lung parenchyma
Pathogenesis of ascites in cirrhosis
What travel through the jugular foramen
CN IX, X, XI, jugular vein
What. is. porphyrea cutanea tarda
Deficiency in uroporphrynogen decarboxylase, distrupts heme synthesis
causes photosensitivity. - vesicles
How is drug delivery to the brain improved
Helping cross the BBB by distrupting tight junctions
Stopping cellular eflux transporters like inhibiting p-glycoprotein
How to tell if anisacoria (pupil size difference) is due to PNS or SNS dysfunction
If worse in dim light - SNS disturbance, affected pupil cant dilate
If worse in bright light - PNS, affected pupil cant constrict
Recombination vs reassortment
Recombination is crossing-over and swapping of genetic material between nonsegmented viruses
Reassortment is with segmented viruses
Impact of aging on bone marrow
Increased bone marrow fat and decreased BM mass
Breath sounds, fremitus, resonance
Impact of kidney disease on vitamin d, phosphate, and PTH
How is the G1 to S phase regulated
Regulated by cyclin dependent kinases (CDK4/6). Cyclin D binds CDK and activates it to phosphylate Rb tumor suppresor gene. This. phophorylation inhibits Rb. and allows the cell cycle to go forward
Lithium side effects
LMNOP
Lithium
Movement problems
Nephrogenic diabetes insipidus
hypOthyroidism
Pregnancy (ebstein)
How to diagnose mucormycosis vs asperigilosus
Mucosal biopsy.
Mucor is non-septate with. right. angles along vessels
Apergillus is septate with acute angles
Where is norepinephrine produced
Mainly produced in the locus ceruleus - pigmented cells in posterior rostral pons near floor of fourth ventricle
What are snRNAs/U-RNAs
Form of RNA with lots of uracil that helps to splice out exons (forms splicesome)
What enzyme adds amino acids to tRNA
Aminoacyl-tRNA synthetase
What triggers maturation into Th1 cells
Macrophages with MHC II present to Th0 cells with IL-12 that then differentiate into Th1 cells
Path of embolis that causes retinal artery occlusion
Internal carotid –> opthalmic artery –> retianl artery
What is a rectocele
Herniation of rectum into posterior vaginal wall due to weakened pelvic floor (levator ani)
Relative risk equation
Use for a cohort study
RR = (risk of disease in exposed)/(risk in unexposed)
Short and intermediate acting benzos
Long acting benzos
What happens to BP and SVR during exercise
There is only a mild elevation in BP becuase of large drop in SVR - local metabolites cause vasodilation
Manifestations of chikungunya
What is hemolytic uremic syndrome (HUS)
Shiga toxin samages epithelium. (glomerular damage) that causes microthrombi that consume platelets and damage RBC - shistocytes
How is calcium pumped out of cardiac cells after contraction
Pumped back into SR using SERCA (Ca2+ and ATP)
Pumped out in exhange for Na+ using NCX (1 ca = 3 na)
Where is potassium during DKA
Potassium is driven out of the cells into the plasma, so low intracellular and high/normal extracellular
Insulin will drive potassium back into cells so also have to monitor potassium and give as needed during therapy
TX for serotonin syndrome
Cyproheptadine
TX for benzo overdose
Flumazenil
Duration of pharmacological insulin
Histology as you moved down the airway
Bronchi have a ciliated pseudostratified columnar epithelium with mucin-secreting goblet cells and submucosal mucoserous glands.
The airway epithelium gradually changes to ciliated simple cuboidal by the level of the terminal bronchioles.
Bronchioles lack glands and cartilage, and the number of goblet cells decreases distally, ending before the terminal bronchioles.
Ciliated epithelium persists up to the respiratory bronchioles.
Progression of p53 to Rb
Double stranded break activates p53, which induces p21. p21 inhibits CDK-cyclin complex. This leads to hypophosphorylation of Rb and cell cycle arrest
Occurs at G1-S
What is Li-Fraumeni syndrome
Mutation in TP53 that encodes for p53 leads to inhibition of cell cycle arrest due to damage = accumulation of damage and malignancy
In the golgi:
_____ added to asparagine
_______ added to serine and threonine
_______ added to lysosomal proteins
N-oligosaccharides added to asparagine
O-oligosaccharides added to serine and threonine
Mannose-6-phosphate added to lysosomal proteins
What is I-cell disease
Defect in Golgi (trans) of the enzyme that adds phosphate to mannose-6-phosphate. This causes a defect in adding proteins to lysosomes and proteins are secreted extracellularly.
Coarse features, gingival hyperplasia, clouded cornea, restricted joints, high plasma levels of lysosomal enzymes
Coating of vesicles and where they go (clathrin, CopI/II)
Clathrin - bw plasma membrane and golgi
COPI - Golgi to RER
COPII - RER to golgi
Function of three types of filaments
Microfilaments - muscle contraction (actin), cytokinesis
Intermediate - maintain cell structure (messed up in many cancers)
Microtubules - movement, cell division
What is kartagener’s syndrome
Triad of symptoms seen in Primary Ciliary Dyskinesia 0 dyniene messed up, cilia cant beat
- Chronic sinusitus
- Brinchiectasis
- Situs inversus
Also see infertility
Mneumonic for collagen types
Be So Totally Cool, Read Books
1 - Bone, Skin, Tendons
2 - Cartilage
3 - Reticulin (blood vessels)
4 - Basement membrane
Main components of collagen
Glycine, proline, lysine
Gly-X-Y
Steps in collagen synthesis
- hydroxylation of pro alpha chains (vitamin C)
- Glycosylation and forming triple helix (OI)
- exocytosis and cleavage of terminal ends
- Cross links (Menkes)
Osteogenesis imperfecta mutations
COL1A1 and COL1A2
Type 1 collagen
Elastin components
Non-hydroxylated and non-glycosylated proline, glycine, lysine
What causes Marfans
FBN1 mutation on chromosone Fifteen causes defect in Fibrillin
See constellation of Sx:
Mitral valve prolapse, aortic dissection and aneurysm, lens subluxation (up and out)
What is McCune-Albright syndrome
Example of mosaicism (cells have to be mixed to survive)
Gs-protein activating mutation, see precocious puberty, fibrous growth in bones, cafe au laet spots
Steps pf meiosis
Where are oocytes arrested in oogenesis
Primary oocyte arrested in Prophase of meiosis I
At puberty, a few secondary oocytes arrest in metaphase of meiosis II
Completion of meiosis II at fertilization
What is a robertsonian translocation
Frequent cause of trisomy 21, often 14 and 21 (parent is a carrier)
Hardy-Weinberg equation
P2 + 2pq + q2 = 1
p2 and q2 are homozygotes
2pq is heterozygote
If x-linked, male risk = q, female = q2
What is used to screen for neural tube defects
AFP AND Acetylcholineesterase
What is Von-Hippel Lindau
Mutation in VHL gene - overexpression of angiogenic growth factor (like VEGF)
Hemangioblastoma, renal clear cell carcinoma, pheocromocytoma
What is the greatest risk factor for completed suicide
Previous attempted suicide
What are the significance of the colors in melanoma
Red - vessel ectasia (dilation) and inflammation
Black/brown - advancing melanocytes
White - T lymphocytes target and melanocytes regress
What is X-linked aggamaglobulinemia
Mutation in BTK gene that prevents maturation and exit of BM by pre-B cells. Have low B cell and immunoglobulin levels
Susceptible to enteroviruses and encapsulated bacteria
Features of chronic bronchitis
Thickened bronchial walls, lymphocytic infiltrate, mucous gland elargment, patchy squamous metaplasia
Tobacco is strongest predisposing factor
Postpartum mood disorders
Number needed to treat
1/ARR
What is deficient in vegan dieta
Calcium, vitamin d, B12
What is seen in injury to common peroneal (fibular) nerve
Often break of neck of fibula
Loss of dorsal foot sensation, inability to evert foot, inability to dorsiflex
What nerves are present in the cavernous sinus
III, IV, VI, V (opthalmic and maxillary)
Steps in base excision repair
How does Chagas disease lead to megaesophagus and megacolon
Destriction of myenteric and submucosal plexi
Three associated esophagitises associated with HIV
How is blood flow to kidney autoregulated in chronic hypertension
- afferent arteriole reflexesively constrict at higher BP
- High BP leads to hyperfiltration that leads to higher Na and Cl in urine, leading to release of adenosine which further constricts afferent a.
If BP is corrected too rapidly, blood flow to kidney drops and can cause acute tubular necrosis
Effect of BNP and ANP
BNP released by ventricle stretch, ANP by atrial stretch
Cause vasodilation and diuresis
Pathogenesis of anemia of chronic disease
Disease causes release of inflammatory citokines, including hepcidin
Hepcidin binds to iron transporters on enterocytes and macrophages leading to less iron recycling and utilization
less overall circulating iron and total iron binding capacity
What is apnea of prematurity
Central stimulatory neurons of respiratory center are not fully developed, leads to periods of apnea and bradychardia
How does iodide block production of thyroid hormone
Competitively binds to iodine receptor for uptake into thyroid and prevents iodine organification which reduces thyroid hormone release (Wolf-Chaickoff)
Levodopa side effects
Peripheral : nausea, vomiting, tachyarrhythmias, postural hypotension, hot flashes
Central: anxiey, irritation
Difference in PO2 and PCO2 in difdusion-limited perfusion
Due to changes in diffusion like fibrosis, emphysema
High gradient between alveolar O2 and capillary O2 because catn diffuse
Less of a gradient in CO2 because CO2 diffuses much more readily than O2
Normal alveolar gas exchange numbers
TX for beta blocker overdose and MOA
Glucagon
stimulates adrenergic receptors to increae cAMP
Why is reflux common in pregnancy
Elevated estrogen and progesterone decrease LES tone. Later, fetus can compress stomach
What mutation is associated with sebborheic keratosis
Fibroblast growth factor receptor 3
Acromegaly impact on heart
Can lead to ventricular hypertrophy leading to systolic dysfunction and heart failure
What is Prader-Willi syndrome
Paternal allel is deleted or mutation on chormosome 15 - PWS, 25% due to maternal uniparental disomy
Hyperphagia, obesity, hypogonadism, intellectual disability
What is Angelman syndrome
Maternal allele is deleted or mutated on ch 15 - UBE3A
SAIL - seizures, ataxia, intellectual disability, laughter
5% from uniparental oarental disomy
Features of trisomy 21
5 As:
Advanced maternal age, Atresia (duodenal), ASD, Alzhiemers, AML/ALL
Pregnancy screens associated with down sydnrome
Poorly formed nasal bones, nuchal translucency
Increased B-hCG
Decreased PAPP-A and AFP
What is Edwards Syndrome
Trisomy 18
PRINCE : Prominent occiput, rocker bottom feet, intellectual disability, nondisjunction, ears are low set
Also see clenched fist, congenital heart defect
Death usually by 1 yr
Maternal screens seen with trisomy 18
Low PAPP-A and B-HCG
Basically low everything
What is Patau sundrome
Trisomy 13
Cleft palate, holoProsencephaly, polydactyly, cutis apalasia, polycystic kidney disease, heart defect
Also die by 1 yr, low everything
What is Ducehenne muscular dystrophy
X-linked recessive mutation in DMD gene that encodes for dystrophin (frameshift - truncated protein)
What is dystrophin
Binds actin to transmembrane proteins (dystroglycan)
Features od Duchenne Muscular Dystrophy
Myonecrosis - elevated CK and aldolase
Waddling gait, using hands to push. up from chair, weakness
Cardiomyopathy is common cause of death - fibrosis
What is Becker muscular dystrophy
Milder form of Duchenne’s caused by non-frameshift mutation so get abnormal protein instead of truncated
What is Fragile X syndrome
X-linked dominant tinucleotide repeat (CGG) in FMR1 gene. Causes hypermethylation and less expression
Intellectual disabilities, long face, everted ears, mitral valve prolapse, hypermobile joints
What is Freidrich’s Ataxia
GAA repeat in frataxin gene, Autosomal recessive
Ataxic gait, hypertrophic cardiomyopathy
What is myotonic dystrophy
CTG repeats in DMPK gene, autosomal dominant, progressive muscle. wasting with prolonged contractions
Cataracts, balding, hypogonadism, arrhythmias
What is cri-du-chat syndrome
deletion of part of hsort arm of chromosome 5
Intellectual disability, infant has high pitched cry (like cat), microcephaly, cardiac (VSD)
What is Williams syndrome
Deletion on part of chromosome 7, partially for gene for elastin
Elfin features, intellectual disability, extreme friendliness with strangers, supravalvular aortic stenosis, hypercalcemia
Kleinfelter’s
Usually 47 XXY - nondisjunction during meiosis. of either parent
Hypogonadism (low testosterone but high FSH, LH)
Gynecomastia, delayed puberty, low body hair and sperm count
Turner Syndrome
Females 45 XO, can be mosaic 45X/46XX if mitotic nondysjunction in zygote
Short stature, broad chest, webbed neck, lymph obstruction, hypogonadism (streak ovaries), low inhibin b and estrogen (high LH and FSH)
Primary ammenorhea, bicuspid aortic valve, coarctation of aorta, high bp, horseshoe kidney, osteoporosis
What is supplied by the inferior mesenteric artery
Hindgut derivatives - distal 1/3 transverse, descending, sigmoid colon, and rectum
What dictates the severity of mitochondrial disorders
Heteroplasmy - some cells may recieve many damaged mitochondria and others very few
Dobutamine MOA
Beta adrenergic agonist, especially in the heart.
Increases contractility and heart rate, increasing Oxygen demand. Small decrease in BP (vasodilation)
Where are actin and myosin
What DNA viruses are enveloped
Hepadnavirus
Herpesvirus
Poxvirus
Describe the complement system
Pathophys of tetrology of fallot
Abnormal neural crest cell migration that leads to deviation of the infundibular septurm.
- overriding aorta
- VSD
- Right pulmonary obstruction
- Right Ventricle hypertrophy
V/Q ratio as you move down the lung
Ventilation/Perfusion(Q) is lowest at the base and highest at the apex
Ventilation is slightly higher in the base and slightly lower in the apex (gravity changes complaince). Perfusion is very high in the base and very low in the apex
Common sites of globe fractures
Medial into ethmoid air cells
Inferior into maxillary sinus
What does the mandibular nerve (CN V3) innervate
TMJ, floor of mouth, anterior tongue, lower part of face, tensor tympani (muffles sound), muscles of mastication
How does the lac operon in E. Coli work
What is the diptheria toxin
An AB toxin
Inhibits cell protein synthesis by catalyzing ATP-ribosylation on EF-2
Heparin MOA
Binds to antithrombin III
Then binds Xa and thrombin
What are RANK-L and OPG (osteoprotegrin)
RANK-L binds RANK on osteoclasts and increases formation and activity
OPG binds to RANK-L and stops it from inducing osteoclasts = less osteoclast function
Histo features of an aortic aneurysm
Cystic medial degeneration - smooth muscle replaced by basophillic extracellular matrix znd elastic fragments w cysts
What is achondroplasia
Limb shortening with a normal torso due to overexpression of FGFR3 gene that inhibits chondrocyte formation
What leads to formation of testosterone and inhibin
GnRH –> LH. –> Testosterone
GnRH —> FSH –> inhibin
What is the odds ratio
The odds of disease of exposed individuals vs non-exposed individuals
How does digoxin slow HR
Increased parasympathetic (vagal) tone
What does CD14 bind
Macrophages
Markers for natural killer cells
CD16 and CD56
Function of glucagon-like peptide 1
Secreted by gastric L cells, stimulates release of insulin and decreases glucagon
MOA of DPP-4 ihibitors
Stop the breakdown of GLP-1 (done by DPP-4) so increase the glucose-dependent release of insulin
GLIPTINS
Process of male genital development
Presence of SRY gene on Y chromosome leads to expression of testes-determining factor
Leydig cells = testosterone –> DHT = external and internal (Wollfian) male development
Sertoli cells = anti-mullerian hormone = involution of paramesonephric ducts
How to calculate specificity and sensitivity
Features of anti-glomerular basement mebrane antibodies
Target type IV collagen so see linear deposits of IgG and C3 with RPGN and crescent formation
Functions of the frontal lobe
Executive functioning (abstraction, impulse inhibition), personality, motor function, language
Features of cerebellar tremor
Action tremor (increases as hand gets closer)
ataxia, gait disorder
Seen most commonly in multiple sclerosis
Vitamin supplements for infants
Vitamin D (low in breast milk, usually low sun)
Vitamin K (given as shot at birth)
Iron (greater than 4 months, low weight)
MOA of fibrates
Activate PPAR alpha leading to decreased VLDL production and increased LPL function
Function of Th1 T cells vs Th2
Both are CD4 T cells
Th1 - “cell mediated” immunity, activate macrophages and CD 8 cells. Also B cells
Th2 - “humoral” immunity, activate B cells to produce IgE and IgE
Anti-inflammatory cytokine
IL-10
Infections that need TH1 response
Intracellular - TB, listeria
Relatiosnhip bw macrophages and Th1
Th1 produce IFN- gamma that activates macriphages
Macrophages produce IL-12 that activate Th1
Deficiency: mycobacterium infections
Function of granzymes
Activate caspases that lead to cell apoptosis
Present in CD8 T cells
Function of Th17 cells
Important for GI bacteria regulation
Induce neutrophullic inflammation
What is the AIRE gene and deficiency
Autoimmune regulator in thymus
Without AIRE get CHAR
chornic candidiasis, hypoparathyroidism, adrenal insufficiency, recurrent candida infections
B cell surface proteins
Self cell markers that block complement
Decay Accelerating Factor (DAF/CD55)
CD59 inhibits MAC
Risks associated with early complement defifiency
Low C1 - C4
Pyogenic sinus and respiratory tract infections
Risks associated with late complement defifiency
Low C5-C9
Susceptible to Neisseria
What is C1 esterase inhibitor deficiency
Causes activation of C1 leading to low C4. Causes high bradykinin that leads to angioedema
Formation of leukotrienes, prostoglandins, and thromboxanes
What is erythropoeitin
Released by renal cortex and medula during hypoxia that stimulates BM to produce more RBC, increasing. capacity for oxygen
Which non-glucose monosacchride is metabolised fastest
Fructose, bypasses PFK-1 in glycolysis
Most common cause of pathologic nipple discharge
Intraductal papilloma
See epithelial and myoepithelial cells lining a vascular core
Function of interferon alpha and beta
Produced by virally infected epithelial cells, bind to neighboring cells that are induced to make antiviral RNA enzymes - target double stranded RNA for destruction
Location of purely sensory strokes
ventral posterior thalamus
Neonatal tetanus prevention
Vaccinating women with inactivated tetanus toxin, will pass IgG on to baby
MOA of the four TB drugs
Treatment for PID
Have to treat for both gonorrhea and chlamydia
Third gen cephalosporin for gonoccocal
Azithromycin or doxy for chlamydia (not suscpetible to beta lactams)
Features of hypertrophic cardiomyopathy
Hypertrophic interventricular septum that can block outflow
See increased LV mass, decreased LV volume, preserved ejection fraction, impaired LV relaxation
Causes of premature cataracts
Glucorticoids (predisone)
DM II
trauma
radiation
Function of kinesin
Move vesicles along microtubules from - to + which means away from the nucleus (like towards nerve terminals)
Most common cause of fetal hydronephrosis
Narrowing of ureter at the uretropelvic junction
Stroke mechanisms in context of cocaine
- Cerebral vasospasm
- BP increased and sympathetic tone increased, can lead to dissection and rupture of small vessels
- Increased activation of platelets
Changes seen in distributive shock
Seen in widespread vasodilation (anaphylaxis)
Decreased SVR, decreased PCWP (lower volume), decreased venous return (CVP)
MOA of shiga toxin
AB toxin
A portion stops protein synthesis leading to death of mucosal cells. Stops binding of tRNA to 60s subunit
Promoter regions on DNA
TATA is 25 nucleotides from transcription
CAAT is 75
How to calculate alveolar ventilation
(tidal volume - dead space) x RR
What is superior mesenteric artery syndrome
When the transverse protion of the dudoenum is traooed between SMA and aorta
Can be due to diminished fat, burns, lordosis
Effects of Vasoactive intestinal peptide
Stimulates pancreatic bicarb and chloride secretion, increased cAMP in intestinal cells that causes release of sodium, chloride, water secretion into bowel
What is seen in a VIPoma
WDHA syndrome - watery diarrhea, hypokalemia, achlorhydria
What causes a narrowed mediastinum on neonatal XRay
Transposition of great arteries
Examples of drugs that directly stimulate dopamine receptors
Ergot alkaloids: bromocriptine
Nonergots: pramipexole, ropinirole
MOA of senna and bisacodyl
Stimulant laxatives
Activate enteric nerves in myenteric plexus to induce peristalsis
What is calcineurin
Dephosphorylates nuclear factor of activated T cells (NFAT) that moves to the nucleus to induce production of IL-2 (activate more T cells)
Probablity of exact HLA match between siblings
25 %
2 genes - 1 each from each parent
What is graft vs host disease
Grafted T cells proliferate in host and see host cells as foreign - type IV hypersensitivity
Rash, jaundice, diarrhea, hepatosplenomegaly
What is DiGeorge Syndrome
Failure to develop 3rd and 4th pharyngeal puches due to 22q11 deletion
Lack of thymus - T cell deficiency
Lack of parathyroid - hypocalcemia
What is Severed combines immunodeficiencies
Cytoline receptor defectors
Adenosine deaminase deficiency (nucleotide salvage pathways)
MHC II deficiency
RAG mutation - VDJ recombinant deficient
X-linked agammaglobinemia
Defect in BTK tyrosine kinase gene
No B cell maturation so no Ig
Pathophys of hyper IgM syndrome
There is a defect on the CD40 receptor so B cells cant activate helper T cells - only produce IgM
T cells dont produce IL-4 and IL-5 that induce class swithcing so low IgE, IgA, IgG
Reccurent pyogenic infections and mucosal infections
What is wiskott aldrich syndrome
WATER
Thrombocytopenia, eczema, recurrent infections
Mutatoin in WAS gene (defective cytoskleton and antigen presentation)
X-linked
What do the paramesonephric ducts. form
They fuse laterally to form the fallopian tubes, uterus, cervix, and upper vagina
Where is robosomal rna found
Nucleolus
What are P bodies
Structures found in cytoplasm that play a role in mRNA regulation and turnover - can cause translation termination and storage of mRNA
How does cortisol attenuate hypoglycemia
During a prolonged fast, cortisol is released and diffused across cell membranes. In the cytoplasm it binds to receptors bound to heat shock proteins. The receptor is release from the HSP and dimerize. They move into the nucleus and induce gluconeogenic. enzyme production
Treatment for turners syndrome and MOA
Growth hormone
Binds to JAK receptor in the liver and activates STAT which goes to the nucleus to induce production of IGF-1
Gonadotropin regulation in males
Features of aortic regurgitation
Diastolic decrescendo murmur
Bounding femoral and carotic pulses - widened pulse pressure
Bobbing head - stronger LV
What is trendelenburg sign
Hip drop with foot raise on contralateral side fue to weakness of gluteus medius/superior gluteal nerve
Due to giving shots superomedial - should give superolateral
How is bioavailability calculated
Area under the curve of the route / area under IV curve
TX for toxo encephalitis
pyramethamine and sulfadiazine (or clinda)
What is primary central nervous system lymphoma
Second most common cause of ring enhancing lesions in HIV - usually solitary
Caused by B cells - usually with EBV
What vitamins do gut bacteria produce
Vitamin K and folate
Can be overproduced in Rou-en-Y procedure that produces blind ended gastric pouch
Brain features od Alzheimers
Neurodegeneration, B-amyloid plaques, neurofibrillary tangles
Mneumonic for reflexes
S1 S2 buckle my shoe
L3 L4 kick the door
C5 C6 Pick up sticks
C7 C8 lay them straight
Process of platelet plug formation
VWF bind platelets on exposed epithelium
Platelet is activated and releases TXA2 to cause vasoconstriction, more substances released to form clot
Prostacyclin (PGI2) and NO oppose formation
How to measure for primary hypothyroidism
Use TSH levels because small changes in thyroxin cause large changes in TSH - can drop before thyroxin drop is noticeable
What two factors stop fungal infections
T cells stop sueprficial fungal infections (skin)
Neutrophils stop hematogenous fungal infections
Common pathogens seen in cystic fibrosis
Staph aureus, H. Flu, Pseudomonas aeurigonas, Burkholderia capacia
MOA of loop diuretics
Block NaK2Cl transporters
Can cause metabolic alkalosis because losing more Cl- –> body becomes less negative so holds onto HCO3-
Can give carbonic anhydrase inhibitor (acetazolamid) to lose bicarb
MOA of verinicline
Partial agonist of nicotine receptor – lowers cravings for tobacco and attenuates response to it
What is Fas ligand
Produced by T cells that keep reacting to self antigen. Binds to CD95 and causes apoptosis
Phenotype of regulatory T CELLS
CD4CD25FOXP3
What lupus tests are specific and which are sensitive
Specific : anti-dsDNA and Anti-Sm
Sensitive: Anti-ANA
Why can people with lupus have a false positive lupus test
People with LES can have anticardiolioin antibodies (type of antiphospholipid) that is used to test for syphillis (released by damaged cells)
Common causes of drug induced SLE
Hydralazine, isoniazid, procainamide
Pathophys of sjogrens
Lyphocytes - Type IV hypersensitivity
Destruction of salivary and lacrimal glands
Common comorbidity with sjogrens
Rheumatoid arthritis
Will have rheumatoid factor in blood
What causes neonatal lupus
The Anti-SSA ribonucleoprotein, crosses the placenta and can cause heart block
What is systemic sclerosis (scleroderma)
Autoimmune damage of vessels
Endothelial damage leads to inflammation and inflammation - increased endothelin, TGF -beta, PDGF
Leads to fibrosis
What amino acids cant be absporbed in cystinuria
cysteine, lysine, ornithine, arginine
COLA
Get cystine stones (hexagon)
What is Rett syndrome
X-linked condition marked by normal development until 6-18 months then regression of speech, repetivive hand movements, gait abnormaities
MECP2 gene causes arrested brain development
What can cause malaria despite prophylaxis
P. Falciparum is resistant to chloroquine, have to give mefloquine
The larvae live in schizonts inside the liver for up to 30 days, mefloquine only works in the blood. If stop before 30 days, can develop malaria
Course of the ureters
From kidneys, pass posetrior to gonadal vessels, then anterior to the internal ileac, then posterior to uterine artery
Describe the Ras pathway
Growth factors bind to a tyrosine kinase which converts GDP bound to inactive Ras to GTP, making active Ras. Ras then activates MAP kinase that goes to the nucleus
Impact of hypothyroidism on lipids
Hypothyroidism causes a decrease in the number of LDL receptors leading to higher LDL
Also have decreased activity of lipoprotein lipase so high triglycerides
Role of CTLA4
Blocks CD80 on APC which stops interaction with CD28 on T cells, causing anergy
What determines the maintenance dose
Steady state cocentration x clearance x interval
What is leukocyte adhesion deficiency
Deficiency in CD18, WBCs cant roll and migrate
see late separation of the umbilical cord, low pus, dysfunctional neutrophils
Glucorticoids MOA
Inactivation of NF-KB, a key inflammatpry transcription factor
Cancer associated with Sjogrens
B cell lymphoma - will see unilateral parotid gland enlargment
What is scleroderma and manifestations
Systemic sclerosis - vasculopathy, collagen deposition, fibrosis
Diffuse - skin, early visceral, kidney (use ACE)
Limited - CREST (calcinosis, anti-centromere antibody, raynauds, esophageal dysmotility, sclerodatyly, telangesctasia)
What is Potters sequence
Oligohydramnios causes Flat face, limb deformities, pulm hypoplasia
Odds ratio calculation
(a/b)/(c/d)
MOA of rituximab
MAB to CD20 on B cells, leads to reduction in B cells
What WBCs increase in steroid use
Neutrophils - steroids induce them to “demergination” off of vascular wells so get more circulating
What to moitor on testosterone therapy
PSA (can enlarge prostate)
Hematocrit (can make blood more coagulable)
Four components of informed consent
disclosure, understanding, voluntariness, authorization (documents)
What structures are injured with an anteromedial displacement of humerus
Brachial artery and medial nerve
Organ with the highest oxygen demand
Myocardial tissue
SX of pineal gland tumor
Hydrocephalus (blocks aqueductal obstruction) and Parnaud syndrome (cant gaze upward)
Usually a germinoma
Blood supply of the rectus abdominus
Inferior epigastric arteries
Enters at the arcuate line (above line, m has anterior and posterior sheath. Below, only anterior)
Side effects of succinylcholine
Malignant hyperthermia
Hyperkalemia - K leaks out of cell when polarized
Bradychardia or tachycardia
SX of cholangitis
Fever, RUQ pain, jaundice (charcot triad)
Can have hypotension and altered mental status
Often caused by obstruction of common bile duct
HBV life cycle
HBV has a partially double stranded DNA sequence
Goes into cell and dumps DNA material into nucleus where it is “fixed” by host DNA polymerase and then transcribed by host machinery into + RNA that goes into cytoplasm
RNA is reverse transcribed. by viral reverse transcriptase into the partially double stranded DNA. Host ribosomes make protein capsule
What is alternative splicing
Process by which one gene can code for various proteins - exclusion or inclusion of certain. introns can create a different protein
Pathophys of neonatal respiratory distress syndrome
With inadequate surfactant production by type II pneumocytes, the lungs have a higher surface tension and are less compliant. This cuases atelectasis - can see ground glass opacities
Changes seen in obesity induced restrictive lung disease
Low FEV1, Low FVC, low ERV, can be low TLC
Normal RV
What is beri-beri
Thiamine deficiency
Dry - peripheral neuropathy
Wet - neuropathy and cardiac involvment
Which diuretic to use with heart failure
Spironolactone
Aldosterone blocking can stop heart remodeling
SX of hyperaldosteronsim
Hypertension
Hypokalemia
Metabolic alkalosis
Sodium is retained in exchange for dumping of K and H
See muscle weakness and paresthesias
What organs cant undergo hyperplasia
Pemanent cells - myocytes, skeletal muscle, nerves
Hallmark of reversible cellular injury
Cellular swelliong - loss of microvilli, membrane blebbing, swelling of RER
NA/K pump is inhibited and Na builds up, pulling water in
Hallmark of irreversible cellular injury
Membrane damage - plasma membrane, mitochondrial (cyt c leaks out = apoptosis), lysosomal
Dosing of hydrophilic vs hydroophobic drugs in obese patients
Hydrophilic - lower dose than body weight becuase drug will stay extracellulary - wont go into larger adipose store
Hydrophobic - higher dose, drug has to saturate fat before it can take effect
Origin of melanocytes
Neural crest – Melanoma
Function of TNF-alpha
macrophage activation, phagolysosomes, granulomas
Muscles that control defecation
Internal and external sphincter
Puborectalis muscle
Neuro finding on REM sleep behavior disorder
alpha-synuclein
What impacts creatinine levels
Muscle mass and meat intake
Order of veins off of the SVC
external jugular drains into subclavian then drains into brachiocephalic then into SVC
What CN innervate sensory of ear
V, VII, IX, X
Normal flow of pleural fluid
Into pleaural space from intercostal microvessels, out via parietal pleural lymphatics
Pathophys of TMJ
Dysfucntion of joint, hypersensitivity of mandibular nerve (V3) and muscle spasm (masseter, pterygoid)
SX of typhoid fever
Conditions that make TB more likely
Chronic kidney disease, DM, HIV, immunosuppression
Bone changes in osteoporosis in aging vs hyperparathyroidism
Aging - lamellar bone is reduced
PTH - Cortical thinning (subperiostial)
Pathogenesis of migraines
Cortical spreading depression is allowed by increased cerbreal excitability. The cortical spreading (aura) leads to release of CGRP (calcitonin gene related peptides) that transmit pain and cause vasodilation
Triptans block CGRP
explain transient warfarin hypercoagulability
Protein C and VII have short half lives and are depleted first by warfarin. Protein C is an anticoagulant so allows Vitamin K to go unchecked until depleted
TX for delirium
Treat underlying disease (abx)
Antipsychotics (usually firsy gen - haloperidol)
What is acute intermittent porphyria
Deficiency in PBG deaminase (in porphyrin synthesis)
5 Ps - painful abdomen, Port wine pee, polyneuropathy, psychological disturbances, precipitated by drugs (P-450 inducers)
What is lymphogranuloma venereum
Caused by chlamydia L1-L3
Starts as painless ulcer, then several large painful ulcers along inguinal nodes (boobos)
TX: Doxy
MOA of calcium channel blockers (dihydropyridines vs non)
Effects of ANP and BNP
Kidney: increases GFR, diuresis, renin inhibition
Adrenal: reduce aldrosterone
Vessels: vasodilate and increase permeability
Metabolic effects of glucagon
Primarily increases glycogenolysis
Then decreases glycolysis and increases gluconeogenesis
Process of loss of nucleus
Pyknosis - shrinking
Karyorrhexis - fragmentation
Karyolysis - dissolution
What is coagulative necrosis
Necrotic tissue that remains firm, retains its shape
Proteins coagulate, no nuclei
INFARACTION - wedge shaped
What is caseous necrosis
Friable, cottage cheease like necrosis
Liquefactive necrosis with TB or fungal infection
What is saponification
Calcium deposit on fat necrotic tissue due to binding of calcium to fatty acids
What is metastitc calcification
When there are high serum calcium levels that forces clacium into tissues
What is Bcl2
Stabilized the mitochondrial membrane. Without it Cyt-C leaks out and activates caspases = apoptosis
What are the three free radicals and what degrades each
Superoxide (O2-) – superoxide dismutaes
Peroxide H202 – catalse
OH free radical – glutathione peroxidase
Process of carbon tetrachloride injury
Becomes ccl3 a free radical
Damages hepatic cells = swelling = ribosomes pop off RER so less protein formation
Less apolipoprotein formation = fatty liver
Primary vs secondary amyloidosis
primary - deposition of AL amyloid from Ig light chain
secondary - AA amyloid (from acute phase reactant SAA)
See nephrotic cyndrome, cardiomyopathy, tongue enlargment, hepatosplenomegaly
Features of gardnerella
Thin off-white discharge, positive whiff test
No inflammation
Anaerobic gram-variable, see clue cells
Effect of heart on a-1 agonism
Becuase of vasoconstriction, baroreceptors will cause increased vagal stimulation leading to an inhibition of pacemaker rate
Common features of turner syndrome
How to measure lung maturity of fetus
The phosphotidylcholine/sphingomyelin ratio
Phosphotidylcholine is a component of surfactant so should increase
Sphingeomyelin is a phospholipid and shouldnt increase as much
Location of pneumonia if aspiration lying down vs standing
Always in the right
MOA of sofosbuvir
RNA-dependent RNA polymerase inhibitor
Stops formation of proteins
HCV
Hormonal changes in pregnancy
Most common site of ectopic impulse in A fib
Pulmonary veins
Sounds heard with mitral regurgitation
Holosystolic murmur at apex of heart radiating to axila\
Can produce an S3 - sign of volume opverload in LV
Where are gastric parietal cells located
Upper glandular layer
Serotype associated with reactive arthritis and SX
HLA-B27
