Revalida PRMLE1 Review.

Aminoácido esencial
Los 9 aminoácidos esenciales son:

1. histidina

2. isoleucina

3. leucina

4. lisina

5. metionina

6. fenilalanina

7. treonina

8. triptófano

9. valina
PKU
Phenylketonuria (PKU) is an autosomal recessive disorder caused by defects in metabolizing phenylalanine to
tyrosine.

Excess phenylalanine is converted into phenylketones in the urine, giving rise to the name, phenylketonuria. PKU
can be caused by defects in phenylalanine hydroxylase or its BH4 cofactor. Since tyrosine cannot be produced
from phenylalanine, tyrosine becomes essential in the diet.

Clinical features include seizures and cognitive delays. Growth retardation and failure to thrive is observed, and

on exam, patients will often have a light or fair complexion, eczema, and a characteristic musty body odor.
Diagnosis is delayed 2-3 days after birth since infants are normal at birth due to the presence of maternal enzymes.
OTC Def.
Ornithine Transcarbamylase Deficiency is the most common disorder of the Urea Cycle.

Inherited in an X-linked recessive pattern, affected patients will have elevated

ammonia (hyperammonemia), manifesting as lethargy and asterixis. Other laboratory findings
include a decreased BUN, elevated carbamoyl phosphate, and elevated orotic acid.
G6PD Def.
G6PD Deficiency is a X-linked recessive disorder that causes episodic breakdown of red blood cells.

Specifically, the disease is caused by decreased activity of glucose-6-phosphate dehydrogenase or G6PD (see HMP/Pentose

Phosphate Shunt - coming soon!), which converts glucose-6-phosphate to 6-phosphogluconate. More importantly, G6PD normally
produces NADPH for the cell, and patients with G6PD have low NADPH levels intracellularly.

Decreased NADPH prevents the reduction of GSH (glutathione), which typically scavenges free radicals produced by oxidative
stress. Red blood cells (RBCs) are particularly affected, and hemolysis occurs due to oxidative damage.

Patients experience episodic hemolysis when exposed to oxidizing agents (e.g. fava beans, rifampin), or in the setting
of infection (e.g. upper respiratory infection). Blood smears of affected patients will reveal Heinz bodies, precipitated hemoglobin
deposits in RBCs, as well as the presence of bite cells (degmacytes), caused by the removal of Heinz bodies by splenic
macrophages.
Genetic Pedegree
Cori Disease
called glycogen storage disease type III (GSD-III) or Forbes disease, is an autosomal
recessive lysosomal storage disease caused by a deficiency of an enzyme
called glycogen debranching enzyme, also called alpha-1,6-glucosidase.

The deficiency of debranching enzyme leads to the accumulation of branched glycogen

chains (limit dextrins) in the lysosomes of cells of various organs. Symptoms
include hepatomegaly and hypoglycemia.
LDL receptor deficiency
Familial Hypercholesterolemia, also called Type 2 Dyslipidemia, is a lipid disorder caused by
an autosomal dominant defect in the LDL receptor or Apolipoprotein B-100 (Apo B-100).

These defects prevent the binding and removal of low-density lipoprotein cholesterol (LDL) from

the bloodstream.

LDL cholesterol (colloquially, "bad cholesterol") is elevated on labs and may deposit in various tissues.
Cutaneous deposition is seen as Achilles tendon xanthomas. Other relevant findings include corneal
arcus (white ring in cornea). Vessel deposition can lead to accelerated atherosclerosis, and patients
may experience myocardial infarction ("heart attacks") as early as the second decade of life.
LDL receptor deficiency
Type II hyperlipoproteinemia       

•pathophysiology
•deficiency in LDL receptors
•type IIa (familial hypercholesterolemia) results in ↑↑↑↑ LDL
•>260 mg/dL
•see Cholesterol topic
•type IIb (familial combined hyperlipidemia) results in ↑↑↑↑ LDL, TGs, cholesterol
•presentation      

•deposition of cholesterol in normal tissue

•xanthomas
•xanthelasma
•↑↑ risk for coronary heart disease
Xeroderma Pigmentosum
(XP) 
is a rare skin disorder causing extreme sensitivity to sunlight, premature skin ageing, and an increased risk for
skin cancer.

Xeroderma Pigmentosum is caused by a defect in nucleotide excision repair, which is a DNA repair process
used to remove thymine dimers (T-T dimers) created by UV light damage.

The clinical presentation includes extreme sensitivity to sunlight with rapid skin damage and burning,
an increased risk for skin cancers, and the development of corneal ulcers. Since there is no definitive treatment,
patients with Xeroderma Pigmentosum simply have to avoid exposure to UV light.
Ehler-Danlos Syndrome
(EDS) 
describes a group of inherited disorders caused by defects in collagen. While there are many causes, important causes include defects
in tropocollagen cleavage or in cross-linking during collagen synthesis. There are 3 major types of EDS that are well-studied, and
therefore high-yield for exams:

The Hypermobility type of Ehlers-Danlos presents with joint instability only.

The Classical type of Ehlers-Danlos presents with both joint hypermobility and skin hyperextensibility. The classical type results
from defects in Type V collagen.

Lastly, the Vascular type of Ehlers-Danlos results from defects in Type III collagen, and can present with complications such
as aortic dissection, berry aneurysms, and rupture of organs, especially uterine rupture in pregnancy.

All the above subtypes of EDS are associated with mitral valve prolapse.
Retículo endoplásmico liso
– lugar donde se sintetizan los esteroides y detox de drogas y venenos
Cystic Fibrosis 
is an autosomal recessive inherited disease affecting the lungs and digestive system. A defect of a chloride channel
leads to extremely thick mucus secretions, which congest the airways and ducts of the GI tract.

It is typically caused by defects in the CFTR gene on chromosome 7, which encodes a transmembrane chloride

channel. The most common mutation is a deletion of phenylalanine at position 508 (Phe508). This deletion
causes misfolding of the chloride channel, which is then retained in the RER instead of being transported to the
plasma membrane.

Since CFTR works to reabsorb chloride at the skin, patients with CFTR have increased sweat chloride, a finding
which is often used as a common diagnostic test for cystic fibrosis. Contrastingly, CFTR works to secrete chloride in
the GI tract, leading to eventual secretion of sodium and water. As such, defects in CFTR can lead to deficiencies in
pancreatic duct secretions (see Cystic Fibrosis Complications - coming soon!).

Other test results pointing to a diagnosis of cystic fibrosis include increased blood trypsinogen on neonatal screening,
as well as a negative transepithelial potential difference.
Cystic Fibrosis 
Cystic fibrosis is an inherited disorder caused by a mutation in the CFTR chloride channel. Meconium ileus may be seen in
newborns, and can be the first clue in establishing a CF diagnosis.

Patients can also present with recurrent sinopulmonary infections, such as pneumonia and sinusitis. Viscous, sticky mucus
plugs can make clearance of pathogenic bacteria difficult, increasing the risk of infection by bugs like Pseudomonas and Staph
Aureus. The chronic inflammation may also lead to nasal polyps, a finding of which should prompt a sweat chloride testing in
children. Nail clubbing is also commonly seen in association with all the pulmonary issues.

Infertility commonly occurs due to blockage or absence of the vas deferens in males, and thickened cervical mucus in females.

Pancreatic insufficiency can be caused by blockage of the pancreatic ductules. Digestive enzymes become clogged up in the
pancreas, which may result in the cysts and fibrosis for which the disease is named. The lack of pancreatic digestive enzymes
also leads to steatorrhea. This pancreatic insufficiency also results in malabsorption of fat soluble vitamins--notably vitamin
K--which can cause coagulopathy. To help aid digestion, CF patients can take enzyme supplements before eating.

Treatment options for cystic fibrosis focus on preventing these complications from developing in the first place. Azithromycin
can be used to minimize inflammation, thereby reducing the severity of the complications caused by cystic fibrosis.
Achondroplasia
is a congenital skeletal dysplasia that is the most common cause of dwarfism. Achondroplasia is
caused by a gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR3). 

Constitutive activity of FGFR3 impairs chondrocyte (cartilage) proliferation and differentiation,

resulting in shortened extremities and macrocephaly (enlarged head relative to body). In
particular, while long bones rely on endochondral ossification (cartilage-dependent), bones of
the skull use membranous ossification (not reliant on cartilage) and are thus unaffected.
Vitamin K
o Fat-soluble compounds synthesized by intestinal flora
o Includes phytomenadione, phylloquinone, phytonadione
o Vitamin K Deficiency typically caused by fat malabsorption
o Activated by epoxide reductase to reduced form
o Active Vitamin K is a cofactor for the y-carboxylation of glutamic acid residues needed to
synthesize blood clotting factors
o Vitamin K-dependent proteins include Factors II, VII, IX, X, proteins C and S
o Warfarin (Coumadin) inhibits epoxide reductase, blocking vitamin K-mediated gamma-
carboxylation
Disulfiram
bloquea el acetaldehyde dehidrogenase, aumenta el hangover symptoms, discouraging drinking
MCAD Deficiency ® hypoketotic
hypoglycemia 

is an inherited disorder caused by defects in Fatty Acid Breakdown. It is caused by a lack

of medium-chain acyl-CoA dehydrogenase (MCAD), which is involved in the metabolism of
medium-chain fatty acids.

Acyl-CoA Dehydrogenase catalyzes the first step of beta-oxidation, so a defect in its activity leads
to the accumulation of fatty acyl-carnitines and other upstream intermediates.

Due to an inability to use fats for energy, patients develop hypoketotic hypoglycemia during

fasting, and may also present with lethargy, vomiting, seizures, coma, and even death. The
accumulation of fatty acyl-carnitines and ot her intermediates can lead to hepatomegaly and liver
dysfunction, and hyperammonemia may be seen.
 Tetracyclines
Mechanism of action               Clinical use
1. reversibly binds to the bacterial ribosomal 30S subunit, inhibiting • infections
the elongation phase of RNA synthesis by preventing the • gram-positive aerobes
attachment of aminoacyl tRNA to mRNA acceptor site • gram-negative rods
2. accumulates inside bacterial cells, making it good for intracellular • spirochetes
agents • atypical respiratory pathogens
3. bacteriostatic • Mycoplasma
4. absorption inhibited by milk and antacids        • Legionella
5. eliminated via stool • Chlamydophila
• anaerobes
• tick-mediated infections
•dermatologic conditions
Adverse effects 
• acne
1. gastrointestinal upset (most common)
• rosacea
2. discoloration of teeth
•no activity against Pseudomonas
3. inhibition of bone growth in children
•high-yield uses
4. photosensitive rash
• doxycycline is used for
5. teratogenic and contraindicated in pregnancy
• Chlamydia trachomatis
• tick-borne infections (Rickettsia, Borrelia,
Ehrlichia, and Anaplasma)
Vmax
is directly proportional to the enzyme concentration.
Ciguatoxin
Reef fish poisoning (Giguatoxin)
Transmission: ingestion of reef fish containing Gambierdiscus toxicus
o Barracuda
o Sea Bass
o Moray eel
o Amberjack
o Snapper
Mechanism of action: opening of Na  channels; , resulting in depolarization
+

 
Clinical findings
o Cardiovascular: hypotension, heart block, bradycardia
o Gastrointestinal: diarrhea, nausea, vomiting
o CNS: ataxia, vertigo
o Numbness of mouth; lips, extremities
o Reversal of hot and cold sensation
Treatment: supportive
Envenenamiento por tres pasito (raticida)
•Antídoto para neutralizar el efecto tóxico, como la vitamina K.

•Carbón activado por vía oral para absorber el tóxico en el sistema digestivo.

•Laxantes para facilitar la eliminación del tóxico.

•Sueroterapia por vía intravenosa

•Tratamiento sintomático y de soporte vital según los síntomas

Organophosphate Poisoning
•Etiology •Symptoms
• insecticides • salivation, sweating, rhinorrhea, and lacrimation
• e.g., malathion, parathion, and fenthion • involuntary urination or defecation
• nerve gas • nausea, diarrhea, and vomiting
• most rapid and most severe • anxiety
• ophthalmic agents •Physical exam
• e.g., echothiophate and isofluophate • wheezing
• herbicide • from bronchospasm
• e.g., merphos and tribufos • miosis and blurred vision (Pinpoint pupils)
• industrial chemicals • bradycardia and hypotension
• e.g., tricresyl phosphate • fasciculations
•Pathogenesis • seizures
• organophosphates irreversibly inhibit acetylcholinesterase and block the •DUMBBELSS
metabolism of acetylcholine, resulting in increased acetylcholine activity • Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of
• this causes overstimulation of the muscarinic and nicotinic systems, Lacrimation, Sweating, Salivation
receptors
Treatment

•Conservative
• remove clothes and wash the patient
• indications
• for all patients
• for the protection of caregivers and other patients, as organophosphates can
be absorbed through the skin
•Medical
• atropine
• indication
• antidote for all patients as initial therapy (reverse muscarinic effect)
• competitive inhibitor
• pralidoxime
• indication
• antidote for all patients shortly after atropine is given (treat NM dysfunction)
• reactivates acetylcholinesterase
• benzodiazepines
• indication
• for patients with seizures or fasciculations
Myathenia Gravis Mechanism of action of the
Treatment

Anticholinesterase inhibitor
Liquefactive
Filgastrim
•filgrastim

• recombinant human granulocyte-colony

stimulating factor (G-CSF)
• Use: neutropenia: myelosuppressive
chemotherapy, aplastic anemia, congenital
neutropenia
Separation Anxiety Disorder
Separation Anxiety Disorder

•Classified as a type of anxiety disorder

•Overwhelming fear of leaving home or separation from person (e.g., a parent)
• may result in:
• persistent attempts to avoid school
• feigning of symptoms for attention
•Most common onset is between 7-9 years of age
•To diagnose in adults symptoms must last > 6 months
•Treatment 
• cognitive behavioral therapy
• play therapy, family therapy
Physician-aided death
•Physician-assisted suicide

• When a physician supplies a patient with the means to end their own life (e.g., a physician
provides a patient with a lethal dose of morphine that the patient then self-injects)
• Illegal in most states
•Euthanasia

• The active termination of a terminally ill patient's life by a physician to end suffering. (e.g., a
physician injects a lethal dose of morphine).
• Euthansia is illegal in the United States.
•Terminal sedation

• It is legal to adjust medical therapy accordingly to provide relief from pain and suffering in a

patient with terminal illness, despite hastening the patient's dying process (e.g., increasing
doses of morphine in a patient with metastatic cancer)
• Legal and distinct from euthanasia in so far as the intent must be to relieve pain rather than
bring about death, even though it may hasten the dying process.
• Not an appropriate means of addressing primarily existential suffering, e.g., death anxiety.
• Principle of double effect: An ethical principle that legitimizes an act of good intent despite
causing serious harm (e.g. self defense homicide or terminal sedation).
Irrigation del Corazon
Coronary arteries include        
•right coronary artery (RCA)                
•arises from right aortic sinus
•supplies right ventricle and His bundle
•branches
•sinoatrial nodal artery       
•supplies the sino-atrial (SA) node
•right marginal artery
•supplies the right ventricle
•posterior descending artery (PDA) supplies       
•AV node (supplied by atrioventricular nodal artery)
•posterior portion of interventricular septum and ventricles
•posteromedial papillary muscle
•left main coronary artery (LCA)
•arises from left aortic sinus
•branches
•left circumflex coronary artery (LCX) supplies       
•lateral and posterior wall of left ventricle
•anterolateral papillary muscle
•supplies some blood flow to SA node and AV node
•left anterior descending artery (LAD) supplies  
•anterior portion of the interventricular septum
•anterolateral papillary muscle
•anterior surface of the left ventricle
•most common artery to be involved in myocardial infarction
Measurement of the PCWP can help:

•Differentiate between cardiogenic pulmonary edema and noncardiogenic pulmonary edema.

•Confirm the diagnosis of pulmonary arterial hypertension.

•Assess the severity of mitral stenosis.

•Differentiate between different forms of shock.

•Measure key hemodynamic parameters and assess response to therapy.

Capillary Fluid Exchange
Introduction Exchange of Fluids

•Osmosis is driven by Starling forces (hydrostatic and osmotic pressures) 

•Microcirculation • protein contributes to osmotic pressure (noted as oncotic pressure)
• capillaries, the smallest blood vessels, are the site of • filtration
exchange of nutrients, waste products, and fluids • net fluid out of capillaries into the interstitium
• capillaries are thin-walled (a single layer of endothelial cells) and • absorption
allow for the exchange of solutes and gases • net fluid into capillaries from the interstitium
• O2 and CO2 • Starling equation
• simple diffusion through endothelial cells • Jv = Kf [(Pc - Pi) - (πc - πi)]
• water-soluble substancese.g., water, glucose, and amino • fluid movement is determined by sum of hydrostatic and oncotic pressures
acids • variables
• diffusion through aqueous clefts between cells • Kf
• "hydraulic conductance" or water permeability of the capillary wall
Edema • determines the magnitude of fluid movement
•Edema, or swelling • Pc
• ↑ interstitial fluid volume
• occurs when interstitial volume > ability of lymphatics to drain it back into circulation • capillary hydrostatic pressure favors filtration out of the capillary
• from ↑ filtration • Pi
• causes of edema • interstitial hydrostatic pressure opposes filtration
• ↑Pc  • πc
• heart failure
• ↓ πc (↓ plasma proteins) • capillary oncotic pressure opposes filtration
• severe liver failure  • osmotic pressure of capillary blood due to plasma proteins
• failure to synthesize proteins • πi
• nephrotic syndrome • interstitial oncotic pressure favors filtration
• loss of proteins in urine  •the magnitude of fluid movement for a given pressure difference
• ↑ Kf (↑ capillary permeability) • determined by hydraulic conductance (Kf, or water permeability) of the capillary wall
• burn, infection, and toxins
• a release of histamine and cytokines
• ↑ πi
• lymphatic blockage
• filtration out of capillaries exceed the ability of lymphatics to return
fluid to the circulation
Los medicamentos más comunes que se sabe que causan
este tipo de lupus son:

1. Isoniazida.

2. Hidralazina.

3. Procainamida.

4. Factor de necrosis tumoral (FNT) inhibidores alfa (como etanercept, infliximab y adalimumab.

5. Minociclina.

6. Quinidina.
Efecto del K en el Corazon
el potasio reduce el riesgo de ictus e infarto. El potasio es un
mineral que contribuye a la contractibilidad muscular y la
transmisión de impulsos nerviosos y es esencial para la actividad
eléctrica normal del corazón.
Giant Cell Arteritis
Symptoms: Systemic: fever, fatigue, malaise, weight loss.
Headache, Jaw Claudication, Visual disturbance (Ischemic Optic
Neuropathy), Polymyalgia rheumatica.

Dx. Elevated ESR & C-reactive protein. Temporal artery biopsy:

intimal thickening, elastic lamina fragmentation, multinucleated
giant cells

Tx. Glucocorticoids (Methylprednisolone)

Nivel anatomico de los pulmones
T1-T9

Relation of the pulmonary artery to the bronchus at each lung

hilum is described by RALS—Right Anterior; Left Superior. Carina is
posterior to ascending aorta and anteromedial to descending
aorta
Pulmonary Embolism
Obstruction of the pulmonary artery or its branches by foreign material (usually thrombus) that
originated elsewhere. Affected alveoli are ventilated but not perfused (V/Q mismatch). May present
with sudden-onset dyspnea, pleuritic chest pain, tachypnea, tachycardia, hypoxemia, respiratory
alkalosis. Large emboli or saddle embolus A may cause sudden death due to electromechanical
dissociation (pulseless electrical activity). CT pulmonary angiography is imaging test of choice for PE
(look for filling defects) B . ECG may show sinus tachycardia or, less commonly, S1Q3T3 abnormality.
COPD