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Chest pain
First determine which sort of angina it can be classified as based on the explanation of pain by patient and your physical exam:
* Typical angina characteristics = 3:
** Long duration > 20 minutes + Quality: Pressure or crushing
** Provoked by physical or emotional stress
** Relieved by rest or [[Nitroglycerin]] tablets
If 2 or 3 of the following criteria is present, the it is typical angina, if 0-1 present, it is atypical angina.
<br />
{| class="wikitable"
{| class="wikitable"
! rowspan="2" |Cause
|+
! colspan="2" |Diarrhea
|Typical angina characteristics
! rowspan="2" |Age of onset
|Definition
! colspan="3" |History
! rowspan="2" |Physical exam
! rowspan="2" |Lab findings
! rowspan="2" |Additional finding
! rowspan="2" |Cause
! rowspan="2" |Gold standard dignosis
|-
|-
!Watery
|2-3
!Fatty
|Typical angina
!Weight loss
!FTT
!Abdominal pain
|-
|-
|[[Celiac disease (patient information)|Celiac disease]]
|0-1
| +/-
|Atypical angina
| +/-
|}
|Childhood
 
 
Then calculate the "pretest probability of coronary artery disease" based on:
 
* Patient's age
* Patient's angina type
* Patient's gender


Adult
{| class="wikitable"
| +
|+
| +
!
| +
!General
|
!Female
*[[Abdominal distention]]
!Male
*[[Tetany]]
*[[Mouth ulcers]]
*[[Dermatitis herpetiformis]]
*Signs of the fat-soluble [[Vitamin A|vitamins A]], [[Vitamin D|D]], E, and K deficiency
|
* IgA endomysial antibody (IgA EMA)
* IgA tissue transglutaminase antibody (IgA tTG)
* IgG tissue transglutaminase antibody (IgG tTG)
* IgA deamidated gliadin peptide (IgA DGP)
* IgG deamidated gliadin peptide (IgG DGP)
|
*[[Gluten-free diet]]
|
* HLA-DQ2 and/or DQ8 gene mutation
* Innate responses to wheat proteins
|
*Immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) antibody
|-
|-
|[[Lactose intolerance]]
|Low pretest probability of coronary artery disease
| +
|Asymptomatic people of all ages
|Atypical chest pain at age<50
| -
| -
|Adult
|-
| -
|Intermediate pretest probability of coronary artery disease
| -
| +
|
*[[Abdominal tenderness]]
|
* Stool osmotic gap of >125 mOsm/kg
* Stool pH <6
|
*Avoidance of dietary [[lactose]]
*Substitution to maintain nutrient intake
*Regulation of [[calcium]] intake
*Use of [[enzyme]] [[lactase]]
|
|
* Acquired primary lactase deficiency
** Adult-type hypolactasia
** Lactase nonpersistence)
|
|
*Lactose breath hydrogen test
* Atypical chest pain at age>50
* Typical chest pain at age 30-50
|Atypical chest pain in males of all ages
|-
|-
|[[Cystic fibrosis]]
|High pretest probability of coronary artery disease
| -
| +
|Infancy and childhood
| +
| +
| +
|
|
*Digital clubbing
|Typical angina>60
*Respiratory rale, wheeze, and crunckles
|Typical angina at age>40
*Abdominal pain
|}
*Cyanosis
 
|
 
*Positive DNA analysis for CFTR multimutation method
 
*Evaluated nasal transepithelial potential difference (NPD)
Now based on "pretest probability of coronary artery disease", manage patient based on the following table:
|
 
*Disease manifestations in multiple organ systems:
{| class="wikitable"
**Diabetes
|+
**Recurrent upper and lower respiratory tract infections
!
**Infertility
!
|Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein
!
|
!
*Elevated sweat chloride ≥60 mmol/L
!
|-
|-
|[[Laxative abuse|Laxative overuse]]
|Low pretest probability of coronary artery disease
| +
|No additional test is required
| -
|After childhood
|<nowiki>+/-</nowiki>
| -
| +/-
|
|
* enhanced gastrointestinal motility and gastrointestinal sound
* Mild abdominal tenderness
* Abdominal bloating
|
|
* Hypokalemia
* Metabolic alkalosis
* Hypermagnesemia(in case of magnesium laxative usage)
|<nowiki>-</nowiki>
|Laxative drug abuse
|
|
* laxative screening on a stool for:
** Diphenolic laxatives (eg, bisacodyl)
** Polyethylene glycol-containing laxatives
|-
|-
|[[Crohns disease]]
|Intermediate pretest probability of coronary artery disease
| +
|Able to exercise
| -
|No
|Young adults
|Pharmacologic stress imaging testing
 
(20th)
| +
|
| +
|
*[[Abdominal]] [[tenderness ]]when palpated in severe [[disease]]
*Blood seen on [[rectal exam]]
*[[Fever]]
*[[Tachycardia]]
*[[Hypotension]]
|
|
*Topical mucosamine and [[corticosteroids]] are preferred
*[[Mesalamine]] and [[sulfasalazine]] are used for remission
|
|
|
*[[Colonoscopy]] with [[biopsy]]
|-
|-
|[[Hyperthyroidism]]
| +
| -
|
|
|
|
|
|
|Yes
|Does patient have normal ECG?
|
|
*Lump in the neck
*[[Proptosis]]
*[[Tremors]]
*Increased DTR
|
*
|
*
|
|
*[[TSH]] with [[T3]] and [[T4]]
|-
|-
|[[VIPoma]]
|High pretest probability of coronary artery disease
| +
| -
|
|
|<nowiki>+</nowiki>
|
|
|
|
|
|
*[[Tachycardia]]
|}
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
=== Side effects of drugs: ===
 
* Nephrotoxicity → Cephalosporins
* Ototoxicity → Loop diuretics
* Both nephron and ototoxicity→ Aminoglycosides, vancomycin, loop diuretics and cisplatin
* Pseudomembranous colitis → Ampicillin, Clindamycin
 
<br />
 
=== DNA ===
 
 
DNA contains phosphate group, so it is negatively charged because of the negatively charged phosphate groups
 
DNA is composed of nucleotides, which classifies based on their properties to purines and pyrimidines:
 
'''Purine synthesis:'''
 
* You need glycine, glutamine and aspartate + tetrahydrofolate (Folic acid) + CO2
* Rate limiting step : Glutamine PRPP amidotransferase
* Carbon sources:
** CO2, glycine, tetrahydrofolate
* Nitrogen sources
** Aspartate + Glutamine
 
'''Pyrimidines synthesis:'''
 
Aspartate + carbamoyl phosphate (1 carbon and 1 nitrogen [glutamine]) + '''ATP'''
 
* Carbamoyl phosphate → Has 1 carbon and 1 nitrogen
* You need aspartate + CO2 + glutamine + ATP (Last 3 come from carbamoyl phosphate)
* Carbamoyl phosphate synthetase 2 (RATE LIMITING STEP)
* Start with orotic acid then add a base
* Carbon sources:
** Aspartate
** CO2
* Glutamine → Gives nitrogen
 
 
Major bases in DNA: Guanine (G), Cytosine (C), Adennine (A), Thimine (T)
 
* G-C : 3 Hydrogen bonds. Higher melting points
* A-T: 2 Bonds
 
 
Histones are groups of basic proteins found in chromatin. Histone → Contain lysine and arginine
 
Cytosine minus aminogroup = Uracil (Deamination)
 
== RNA ==
Ribosomes are synthesized in the nucleus and transported into the cytoplasm.
 
Ribosomes are made of proteins and rRNA
 
* Eukaryotes → 60 and 40s = 80s
* Prokaryotes → 50 s and 30 s = 70 s
** Have 23s in 50s
 
Translation
 
* Initiation
** IF1, IF2, If3
*** Assist in assembly of smaller ribosomal subunit to first trna molecule
*** Methionine is always the start
*** f-Methionine in prokaryotes
*** IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
** A site → Incoming aminoacyl TRNA binds
** P site → Polypeptide binds (Growing chain)
*** First tRNA binds here
** E site → Free tRNA (exit)
* Elongation
** Incoming charged aminoacyl TRNA binds to A site
** Elongation factor help incoming trna to bind to A site (Uses GTP)
** 50s has peptidyl transferase transfers AA from p site to A site
*** In prokaryotes, activity is in 23s subunit of 50s rRNA
** '''Translocation'''
*** Ribosome complex moves 3 nucleotides
*** tRNA + Peptide is moved from A site to P site
*** Newly uncharged tRNA from P side to E side
*** EF-G  → Eukaryotes
*** EF-2 in eukaryotes
**** Diptheria and exotoxin (Pseudomonas) inhibit this
* Termination
** Stop codons
*** UGA, UAA and UAG
*** Signal to STOP
*** No new TRNA coming
*** Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.
 
<br />
 
==== Orotic aciduria ====
 
* Deficiency of UMP synthase
* AR
* Elevated oritic acid
* Megaloblastic anemia
** Not corrected with B12 or folic acid
* No hyperammonemia
* Treat with uridine
 
==== Ornithine Transcarbomylase Deficiency ====
 
* Causes hyperammonemia
* Elevated orotic acid
* Problem with urea cycle
 
 
Inhibit reuptake of norepinephrine:
 
* Cocaine
* TCA
 
=== GLUT receptors ===
 
==== GLUT 1 ====
 
** Red blood cell, endothelium of RBB
** Low level basal glucose uptake
** No effect from insulin
 
==== GLUT 2 ====
 
** Regulate glucose
** Beta pancreatic and hepatocytes
 
==== GLUT 3 ====
 
** Neurons and placenta
 
==== GLUT 4 ====
 
** Skeletal muscle and adipose tissue
** Insulin DEPENDENT
 
==== GLUT 5 ====
 
** Fructose uptake (In GI tract)
 
 
 
=== Glucolysis ===
Hexokinase and glucokinase → Produce glucose 6 phosphate
 
* Hexokinase → All cells
** Low KM (High affinity)
** Low VMAX
* Glucokinase→ Only in regulators (Liver and beta cells of pancreas)
** High KM
** High VMAX
** Induced by insulin
 
==== Pyruvate kinase deficiency ====
 
* Hemolytic anemia
* Inability to maintain Na K ATP ase
 
==== PFK1 deficiency ====
 
* Elevated fructose 6-P
* Low pyruvate
* High glycogen
 
Regulation of Glycolysis
 
* Fructose 2, 6 biphosphate → From PFK2
* Insulin → Increases PFK2
** Indirectly stimulates PFK1
* Glucagon DECREASES glycolysis
** Stimulates FBPase 2 (Fructose 6 biphophatase 2 → Converts from Fructose 2, 6 BP to Glucose 6 P
 
=== Fasting state ===
 
* Glucagon rises → Activates CAMP → Activation of Protein kinase A
** Phosphorylates FBP2/PFK2 complex → Activating FBP2 and inactivating PFK2
*** FBP2 → Fructose biphosphatase
** Increases F6P and gluconeogenesis
* Well fed state → High insulin → Stimulates PFK2 → Higher levels of F2,6 BP
 
=== Lead poisoning ===
 
* Inhibits delta ALA dehydratase and ferrochelatase
* Degradation of ribosomal RNA
** Basophilic stippling
 
 
Pathology of atherosclerosis
 
* Endothelial dysfunction
** Increasing vascular permeability, thrombosis and increased adhesion
* Accumulation of lipoproteins
** Accumulation of oxidized LDL
* Monocyte adhesion to endothelium
** Migration of monocytes into intima (Transformed to macrophages and foam cells)
*** Foam cells → Macrophages full of lipids
* Factor release
** Inflammation and cytokines
* Smooth muscle cell proliferation
** Extracellular matrix deposition
** Migration of smooth muscle cells into intima
* Lipid accumulation
** Continued accumulation of lipids extracellularly and within macrophages and smooth muscle cells
** Can rupture
 
=== Prinzmetal Angina ===
 
* Coronary vasospasm
* Major risk factor: '''Smoking'''
** '''Seen in younger patients'''
* Pain at rest occurring at night
* Indistinguishable from classic angina
* Diagnosed by coronary ateriography
* Transient ST elevation with no sign of stenosis on arteriography
* Calcium channel blockers → FIRST LINE. Diltiazem
** Nitrates → Second line
* Smoking cessation
 
=== Cytochrome P450 ===
 
==== CYP450 Inhibitors ====
 
** Ciprofloxacin
** Ritonavir
** Amiodarone
** Cimetidine
** Ketoconazole
** Acute alcohol use
** Macrolides
** Isoniazid
** Grapefruit Juice
** Omeprazole
** Sulfanamides
 
==== CYP450 Inducers ====
 
** Phenytoin
** Carbemazepine
** Griseofulvin
** Barbiturates
** Rifampin
** St John’s wart
** Chronic alcoholism
 
Disulfiram Reaction
 
* Inhibition of acetaldehyde dehydrogenase
** Increase aldehyde
** Flushing, sweating, nausea, headache, hypotension
* Causes
** Metronidazole
** Certain cephalosporins
*** Cefotetan
*** Cefamandole
*** Cefoperazone
** 1<sup>st</sup> gen sulphonylurea
*** Tolbutamide
 
Renin
 
* Stimulated by Beta 1 receptors in kidney
* Macula densa sense reduced sodium in glomerular filtrate
* JG apparatus sensing low BP
* Renin cleaves angiotensinogen into angiotensin 1
* Angiotensin 1 becomes 2
** Enzyme: ACE (Angiotensin converting enzyme)
** Produced in the lungs and kidneys
* Angiotensinogen produced by the liver
 
Angiotensin II
 
* Vasoconstrictor
* Stimulates aldosterone secretion
** Causes sodium and water reabsorption
 
BNP
 
* Causes vasodilation
* Increased excretion of sodium and water in urine
 
Splitting


*[[Rash]]
* A2 P2 →Increased split during inspiration
*[[Facial flushing]]
 
*[[Abdominal distention]]
Hand grip
*[[Abdominal tenderness]] in the right upper abdominal quadrant
 
|
* Increases SVR and after load
* Makes MR louder
 
Val salva
 
* Decreases venous return
* Reduces preload and afterload
* Makes HOCM louder
 
Patent Ductus Arteriosis
 
* Associated with rubella
* Indomethacin closes it
 
Carbidopa
 
* Inhibits Dopa decarboxylase
* Prevents conversion from DOPA to dopamine
 
=== Heart Valve problems ===
 
==== Aortic stenosis ====
 
* Ejection click
* Crescendo decrescendo
 
==== Mitral regurgitation ====
 
* Increased by hand grip and squatting
 
==== Mitral valve prolapse ====
 
* Midsystolic click
* Possible systolic crescendo murmur after click
* Valsalva makes murmur start earlier
 
==== Mitral valve stenosis ====
 
* Small pause in the beginning
** Due to initial isovolumetric contraction
* Opening snap
* Heard in apex
** In left lateral decubitus
*** S3, S4, MR heard better on left lateral decubitus
* Caused by rheumatic heart disease
* PCWP is higher than LV diastolic pressure
** PCWP normally  < 12
** LA pressure < 12
** Left ventricular diastolic pressure – Around 10 mm Hg
** Pressure in left atrium is higher → Increasing PCWP pressure
 
==== Aortic Regurgitation ====
 
* Diastolic murmur
* Immediately after S2
* Left side of sternum
* Wide pulse pressure
* Water hammer pulse
* Causes
** Dilated aortic root → Syphillis
** Marfan’s
** Bicuspid aortic valve
*** Most commonly causes AS though
** Rheumatic fever
 
=== Ventricular action potential: ===
 
* Phase 0 → Increased sodium permeability
* Phase 1→ Repolarization. In-activation of sodium channels. K+ channels begin to open
* Phase 2 → Plataeu → K+ open, Ca2+ open
** Causes calcium release from SR and myocyte contraction
* Phase 3 → K+ permeability increased. Closing of calcium channels
** K+ efflux causes repolarization
* ERP
** Cannot potentiate another action potential
 
=== Pacemaker Action Potential ===
 
* Phase 0 → Voltage gated calcium channels open after reaching threshold
** Not due to sodium such as in myocytes
* Phase 3 → Increased potassium permeability
* Phase 4 → Freely permeable to potassium. Gradual depolarization due to sodium channel conductance
*
*
|
 
*[[Dehydration]]
Smooth ER makes steroids, lipids, phospholipids. Involved in detoxifying as well
*[[Lethargy]], [[muscle weakness]]
 
*[[Nausea]], [[vomiting]]
 
*[[Flushing]]
 
|
<br />
|
== Pretest probability of coronary artery disease ==
*Elevated [[VIP]] levels
<br />
*Followed by imaging
{| class="wikitable"
|+
!
!
!Typical chest pain
!Atypical chest pain
!Non-anginal chest pain
!Asymptomatic
|-
|-
|[[Irritable bowel syndrome]]
| rowspan="2" |Younger than 40
| +
|M
| -
|10-90%
|
|10-90%
|
|5-10%
|
|<5%
|
|
*[[Abdominal tenderness]]
*Hard stool in the rectal vault
|
|
*High [[dietary fiber]]
*[[Osmotic]] [[laxatives]] such as [[polyethylene glycol]], [[sorbitol]], and [[lactulose]]
*[[Antispasmodic]] drugs (e.g. [[Anticholinergic|anticholinergics]] such as [[hyoscyamine]] or [[dicyclomine]])
|
|
*[[Diagnosis|Clinical diagnosis]]
**ROME III criteria
**[[Pharmacological|Pharmacologic]] studies based criteria
|-
|-
|[[lactose intolerance]]
|F
| -
|10-90%
| +
|<5%
|
|<5%
|
|<5%
|
|
|
*[[Abdominal]] [[tenderness ]]when palpated in severe [[disease]]
*[[Fever]]
*[[Hypotension]]
*[[Tachycardia]]
*[[Nausea and vomiting]]
|
*[[Bloating|Bloating,]]
*[[Flatulence]]
*Symptoms begin mainly after ingestion of [[lactose]]
|
|
|[[Hydrogen Breath Test|Lactose breath hydrogen test]]
|-
|-
|[[Whipple's disease|Whipple disease]]
| rowspan="2" |40-50
| -
|M
| +
|
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|<nowiki>+</nowiki>
|
*
|
*[[Leukocytopenia]]
*[[Thrombocytopenia]]
|
*[[Skin hyperpigmentation]]
*[[Arthralgias]]
|
|Upper [[endoscopy]] with [[biopsies]] of the [[small intestine]] for ''[[Tropheryma whipplei|T. whipplei]]'' testing ([[histology]] with [[Periodic acid-Schiff stain|PAS staining]], [[polymerase chain reaction]] [[[PCR]]] testing, and [[immunohistochemistry]])
|-
|Allergic enteropathy/Food protein-induced enterocolitis syndrome (FPIES)
| +
| -
|Infancy
| +/-
| +/-
| +
|
*Nausea
*Vomiting
*Abdominal distention
|S/E:
*Blood-tinged and mucusy
*Polymorphonuclear leukocytes presence
|
*triggered by cow's milk protein
*profuse, repetitive vomiting
|
|oral food challenge (OFC)
|-
|[[Eosinophilic gastroenteritis]]
| +
| -
|3rd decade
| +/-
| +/-
| +
|
*Nausea
*Vomiting
*Abdominal distention
|
*elevated serum IgE levels
*abnormal D-xylose test
|
*one-half of patients have other allergic diseases
*associated with an identifiable dietary antigen
|
|
|eosinophilic infiltration of the gastrointestinal tract on biopsy
|10-90%
|10-90%
|5-10%
|-
|-
|[[Microscopic colitis]]
|F
| +
|10-90%
| -
|5-10%
|6th decde
|<5%
| +
|<5%
| -
| +
|
*Abdominal tenderness
|
*autoantibodies include:
**RF
**ANA
**AMA
**ANCA
|
*Fecal urgency
*Incontinence
*My be associated with extraintestinal symptoms, such as:
**Arthralgia
**Arthritis
**Uveitis
|
|
*A colonoscopy with mucosal biopsy with mononuclear infiltrates:
**Collagenous colitis is characterized by a colonic subepithelial collagen band >10 micrometers in diameter
**Lymphocytic colitis is characterized by ≥20 intraepithelial lymphocytes (IEL) per 100 surface epithelial cells
|-
|-
|Congenital chloride diarrhea
| rowspan="2" |50-60
|<nowiki>+</nowiki>
|M
|<nowiki>-</nowiki>
|Neonate
|<nowiki>+</nowiki>
|<nowiki>+</nowiki>
|<nowiki>-</nowiki>
|<nowiki>-</nowiki>
|
*Hyponatremia
*Hypochloremia
*Metabolic alkalosis
|
|
*History of polyhydramnios
*Mutations in the ''SLC26A3'' gene
**Encodes for an epithelial anion exchanger
|
|
|
|
*Excessive fecal secretion of chloride
|5-10%
|-
|-
|Congenital sodium diarrhea
|F
| +
| -
|Neonate
| +
| +
| -
| -
|S/E:
*Alkaline
*Fecal sodium concentrations
Serum:
*Metabolic acidosis
*Hyponatremia
|
*May be associated with choanal or anal atresia
|
|
|
|
|5-10%
|<5%
|-
|-
|Glucose-galactose malabsorption
| rowspan="2" |More than 60
| +
|M
| -
|Infancy
| +
| +/-
| +
|Abdominal tenderness
|
|
|
|
*severe life-threatening diarrhea
*Dehydration
*Symptomatic as long as the diet includes lactose or its hydrolysis products, glucose and galactose
|
|
|
|5-10%
*positive glucose breath hydrogen test + normal intestinal biopsy
|-
|Abetalipoproteinemia
| -
| +
|Infancy
| +
| +
| +
|Abdominal distention
Impaired visual acuity and visual field defects
 
Dysarthria
|Low triglyceride
Low total cholesterol levels
 
Acanthocytes
 
Low vitamin E levels
|Clumsiness
vision impairment
 
Ataxia
|
* autosomal recessive disorder caused by mutations encoding the microsomal triglyceride transfer protein (MTP)
|Clinical findings and low triglyceride and cholesterol level
|-
|-
|Primary bile acid malabsorption
|F
| +
| +/-
|Childhood Adolescents
| +
| +
| +/-
| -
|
|
|Disease hetergenicity lead to varying presentation from chronic diarrhea without significant fat malabsorption to severe watery diarrhea and steatorrhea with malnutrition
|
|
* genetic defects in ''SLC10A2'' (solute carrier family 10 member 2 gene)
|
|
* Total and specific bile acids from stool
|5-10%
* Gamma emitter selenium-75-homocholic acid taurine (SeHCAT)
|-
! rowspan="2" |Cause
! colspan="2" |Diarrhea
! rowspan="2" |Age of onset
! colspan="3" |History
! rowspan="2" |Physical exam
! rowspan="2" |Lab findings
! rowspan="2" |Additional finding
! rowspan="2" |Cause
! rowspan="2" |Gold standard dignosis
|-
!Watery
!Fatty
!Weight loss
!FTT
!Abdominal pain
|-
|Gastrinoma (Zollinger-Ellison syndrome)
| +
| -
|between the ages of 20 and 50
| +
| +/-
| +
|Mild to moderate upper abdominal tenderness
|Positive secretin stimulation test
Elevated serum chromogranin A
|heartburn
|Gastrin producing tumor mainly in duodenum
|elevated basal or stimulated serum gastrin more than 1000 pg/mL
|}
|}
BULLETED
*[[Abscess]]
*[[Acute bronchitis]]
*[[Acute retinal necrosis]]
*[[Adenoiditis]]
*[[African trypanosomiasis]]
*[[Allergic proctocolitis]]
*[[Amoebic liver abscess]]
*[[Anal abscess]]
*[[Aphthous ulcer]]
*[[Appendicular abscess]]
*[[Ascariasis]]
*[[Asymptomatic bacteriuria]]
*[[Atrophic vaginitis]]
*[[Bacterial endophthalmitis]]
*[[Bacterial gastroenteritis]]
*[[Bacterial meningitis]]
*[[Bacterial vaginosis]]
*[[Balanitis]]
*[[Blastomycosis]]
*[[Blebitis]]
*[[Bleb-related endophthalmitis]]
*[[Blepharitis]]
*[[Boil]]
*[[Bourbon virus infection]]
*[[Brain abscess]]
*[[Breast abscess]]
*[[Bronchiolitis]]
*[[Bronchitis]]
*[[Brucellosis]]
*[[Bursitis]]
*[[Candida vaginitis]]
*[[Candidiasis]]
*[[Cervicitis]]
*[[Chagas disease]]
*[[Chicken pox]]
*[[Chlamydia]]
*[[Cholangitis]]
*[[Cholera]]
*[[Chronic bronchitis]]
*[[Chronic diarrhea]]
*[[Cmv infection]]
*[[Coccidiomycosis]]
*[[Colitis]]
*[[Colonic abscess]]
*[[Common cold]]
*[[Congenital cmv]]
*[[Congenital herpes syndrome]]
*[[Congenital infectious landing page]]
*[[Congenital rubella syndrome]]
*[[Congenital syphilis]]
*[[Congenital toxoplasmosis]]
*[[Congenital varicella]]
*[[Conjunctivitis]]
*[[Coxsackie a virus]]
*[[Coxsackie b]]
*[[Coxsackie virus]]
*[[Cryptococcus]]
*[[Cutaneous abscess]]
*[[Cysticercosis]]
*[[Cysticericosis]]
*[[Cystitis]]
*[[Dacryocystitis]]
*[[Dermatophytosis]]
*[[Diphtheria]]
*[[Diphyllobothriasis]]
*[[Diphyllobothrium]]
*[[Diverticulitis]]
*[[Drug-induced proctocolitis]]
*[[Echinococcosis]]
*[[Echinococcus]]
*[[Empyema]]
*[[Endogenous endophthalmitis]]
*[[Endophtamitis]]
*[[Enterobiasis]]
*[[Eosinophilic gastroenteritis]]
*[[Epididymo-orchitis]]
*[[Epiglotitis]]
*[[Erysipelas]]
*[[Erysipeloid]]
*[[Erythrasma]]
*[[Esophageal candidiasis]]
*[[Filariasis]]
*[[Fournier gangrene]]
*[[Fungal meningitis]]
*[[Gardernerella vaginalis]]
*[[Gastroenteritis]]
*[[Gonorrhea]]
*[[Group a streptococcal infection]]
*[[Haemophilus influenzae infection]]
*[[Hand foot and mouth disease]]
*[[Hantavirus infection]]
*[[Helicobacter pylori infection]]
*[[Hepatitis]]
*[[Hepatitis A]]
*[[Hepatitis B]]
*[[Hepatitis c|Hepatitis C]]
*[[Hepatitis D]]
*[[Herpangina]]
*[[Herpes simplex]]
*[[Histoplasmosis]]
*[[Hiv]]
*[[HPV infection]]
*[[Impetigo]]
*[[Infectious colitis]]
*[[Infectious proctocolitis]]
*[[Ischemic colitis]]
*[[Laryngitis]]
*[[Leptospirosis]]
*[[Listeriosis]]
*[[Liver abscess]]
*[[Lung abscess]]
*[[Lymes disease]]
*[[Lymphangitis]]
*[[Mastitis]]
*[[Mastoiditis]]
*[[Meningitis]]
*[[Microscopic colitis]]
*[[Microsporidiosis]]
*[[Molluscum contagiosum]]
*[[Mucormycosis]]
*[[Mycoplasma genitalium]]
*[[Mycoplasma genitalium infection]]
*[[Necrotizing fasciitis]]
*[[Noma]]
*[[Ophthalmia neonatorum]]
*[[Orbital cellulitis]]
*[[Oropharyngeal candidiasis]]
*[[Osteomyelitis]]
*[[Otitis externa]]
*[[Pancreatic abscess]]
*[[Peliosis hepatis]]
*[[Pelvic inflammatory disease]]
*[[Peritonitis]]
*[[Pharyngitis]]
*[[Phlebitis]]
*[[Pleural effusion]]
*[[Post-operative endophthalmitis]]
*[[Post-traumatic endophthalmitis]]
*[[Pott's disease]]
*[[Progressive outer retinal necrosis]]
*[[Prostatitis]]
*[[Psittacosis]]
*[[Pubic lice]]
*[[Pyelonephritis]]
*[[Pyogenic liver abscess]]
*[[Pyomyositis]]
*[[Q fever]]
*[[Radiation proctocolitis]]
*[[Retroperitoneal abscess]]
*[[Retropharyngeal abscess]]
*[[Rhinitis]]
*[[Rhinosinusitis]]
*[[Roseola|Roseola (exanthem subitum)]]
*[[Rotavirus infection]]
*[[Rubella]]
*[[Salmonella enterica]]
*[[Scabies]]
*[[Seborrheic dermatitis]]
*[[Secondary peritonitis]]
*[[Sepsis]]
*[[Septic arthritis]]
*[[Splenic abscess]]
*[[Spontaneous bacterial peritonitis]]
*[[Staphylococcus aureus infection]]
*[[Sexually transmitted disease|S]]TD
*[[Stomatitis]]
*[[Strep throat]]
*[[Strongyloidiasis]]
*[[Syphilis]]
*[[Tetanus]]
*[[Tonsilar abscess]]
*[[Tonsillitis]]
*[[Toxic shock syndrome]]
*[[Toxoplasmosis]]
*[[Trench mouth]]
*[[Trichomonas]]
*[[Trichuriasis]]
*[[Tropical sprue]]
*[[Trypanosomiasis]]
*[[Typhoid fever]]
*[[Typhus]]
*[[Ulcerative colitis]]
*[[Ureaplasma urealyticum]]
*[[Urethritis]]
*[[Uti]]
*[[Uveitis]]
*[[Vaccine mediated polio]]
*[[Vaginitis]]
*[[Viral gastroenteritis]]
*[[Viral meningitis]]
*[[Whip worm infection]]
*[[Wool Sorter's Disease|Wool sorter's disease]]
*[[Zika virus]]

Latest revision as of 22:03, 29 April 2020

Chest pain

First determine which sort of angina it can be classified as based on the explanation of pain by patient and your physical exam:

  • Typical angina characteristics = 3:
    • Long duration > 20 minutes + Quality: Pressure or crushing
    • Provoked by physical or emotional stress
    • Relieved by rest or Nitroglycerin tablets

If 2 or 3 of the following criteria is present, the it is typical angina, if 0-1 present, it is atypical angina.

Typical angina characteristics Definition
2-3 Typical angina
0-1 Atypical angina


Then calculate the "pretest probability of coronary artery disease" based on:

  • Patient's age
  • Patient's angina type
  • Patient's gender
General Female Male
Low pretest probability of coronary artery disease Asymptomatic people of all ages Atypical chest pain at age<50 -
Intermediate pretest probability of coronary artery disease
  • Atypical chest pain at age>50
  • Typical chest pain at age 30-50
 Atypical chest pain in males of all ages
High pretest probability of coronary artery disease Typical angina>60 Typical angina at age>40


Now based on "pretest probability of coronary artery disease", manage patient based on the following table:

Low pretest probability of coronary artery disease No additional test is required
Intermediate pretest probability of coronary artery disease Able to exercise No Pharmacologic stress imaging testing
Yes Does patient have normal ECG?
High pretest probability of coronary artery disease









Side effects of drugs:

  • Nephrotoxicity → Cephalosporins
  • Ototoxicity → Loop diuretics
  • Both nephron and ototoxicity→ Aminoglycosides, vancomycin, loop diuretics and cisplatin
  • Pseudomembranous colitis → Ampicillin, Clindamycin


DNA

DNA contains phosphate group, so it is negatively charged because of the negatively charged phosphate groups

DNA is composed of nucleotides, which classifies based on their properties to purines and pyrimidines:

Purine synthesis:

  • You need glycine, glutamine and aspartate + tetrahydrofolate (Folic acid) + CO2
  • Rate limiting step : Glutamine PRPP amidotransferase
  • Carbon sources:
    • CO2, glycine, tetrahydrofolate
  • Nitrogen sources
    • Aspartate + Glutamine

Pyrimidines synthesis:

Aspartate + carbamoyl phosphate (1 carbon and 1 nitrogen [glutamine]) + ATP

  • Carbamoyl phosphate → Has 1 carbon and 1 nitrogen
  • You need aspartate + CO2 + glutamine + ATP (Last 3 come from carbamoyl phosphate)
  • Carbamoyl phosphate synthetase 2 (RATE LIMITING STEP)
  • Start with orotic acid then add a base
  • Carbon sources:
    • Aspartate
    • CO2
  • Glutamine → Gives nitrogen


Major bases in DNA: Guanine (G), Cytosine (C), Adennine (A), Thimine (T)

  • G-C : 3 Hydrogen bonds. Higher melting points
  • A-T: 2 Bonds


Histones are groups of basic proteins found in chromatin. Histone → Contain lysine and arginine

Cytosine minus aminogroup = Uracil (Deamination)

RNA

Ribosomes are synthesized in the nucleus and transported into the cytoplasm.

Ribosomes are made of proteins and rRNA

  • Eukaryotes → 60 and 40s = 80s
  • Prokaryotes → 50 s and 30 s = 70 s
    • Have 23s in 50s

Translation

  • Initiation
    • IF1, IF2, If3
      • Assist in assembly of smaller ribosomal subunit to first trna molecule
      • Methionine is always the start
      • f-Methionine in prokaryotes
      • IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
    • A site → Incoming aminoacyl TRNA binds
    • P site → Polypeptide binds (Growing chain)
      • First tRNA binds here
    • E site → Free tRNA (exit)
  • Elongation
    • Incoming charged aminoacyl TRNA binds to A site
    • Elongation factor help incoming trna to bind to A site (Uses GTP)
    • 50s has peptidyl transferase transfers AA from p site to A site
      • In prokaryotes, activity is in 23s subunit of 50s rRNA
    • Translocation
      • Ribosome complex moves 3 nucleotides
      • tRNA + Peptide is moved from A site to P site
      • Newly uncharged tRNA from P side to E side
      • EF-G  → Eukaryotes
      • EF-2 in eukaryotes
        • Diptheria and exotoxin (Pseudomonas) inhibit this
  • Termination
    • Stop codons
      • UGA, UAA and UAG
      • Signal to STOP
      • No new TRNA coming
      • Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.


Orotic aciduria

  • Deficiency of UMP synthase
  • AR
  • Elevated oritic acid
  • Megaloblastic anemia
    • Not corrected with B12 or folic acid
  • No hyperammonemia
  • Treat with uridine

Ornithine Transcarbomylase Deficiency

  • Causes hyperammonemia
  • Elevated orotic acid
  • Problem with urea cycle


Inhibit reuptake of norepinephrine:

  • Cocaine
  • TCA

GLUT receptors

GLUT 1

    • Red blood cell, endothelium of RBB
    • Low level basal glucose uptake
    • No effect from insulin

GLUT 2

    • Regulate glucose
    • Beta pancreatic and hepatocytes

GLUT 3

    • Neurons and placenta

GLUT 4

    • Skeletal muscle and adipose tissue
    • Insulin DEPENDENT

GLUT 5

    • Fructose uptake (In GI tract)


Glucolysis

Hexokinase and glucokinase → Produce glucose 6 phosphate

  • Hexokinase → All cells
    • Low KM (High affinity)
    • Low VMAX
  • Glucokinase→ Only in regulators (Liver and beta cells of pancreas)
    • High KM
    • High VMAX
    • Induced by insulin

Pyruvate kinase deficiency

  • Hemolytic anemia
  • Inability to maintain Na K ATP ase

PFK1 deficiency

  • Elevated fructose 6-P
  • Low pyruvate
  • High glycogen

Regulation of Glycolysis

  • Fructose 2, 6 biphosphate → From PFK2
  • Insulin → Increases PFK2
    • Indirectly stimulates PFK1
  • Glucagon DECREASES glycolysis
    • Stimulates FBPase 2 (Fructose 6 biphophatase 2 → Converts from Fructose 2, 6 BP to Glucose 6 P

Fasting state

  • Glucagon rises → Activates CAMP → Activation of Protein kinase A
    • Phosphorylates FBP2/PFK2 complex → Activating FBP2 and inactivating PFK2
      • FBP2 → Fructose biphosphatase
    • Increases F6P and gluconeogenesis
  • Well fed state → High insulin → Stimulates PFK2 → Higher levels of F2,6 BP

Lead poisoning

  • Inhibits delta ALA dehydratase and ferrochelatase
  • Degradation of ribosomal RNA
    • Basophilic stippling


Pathology of atherosclerosis

  • Endothelial dysfunction
    • Increasing vascular permeability, thrombosis and increased adhesion
  • Accumulation of lipoproteins
    • Accumulation of oxidized LDL
  • Monocyte adhesion to endothelium
    • Migration of monocytes into intima (Transformed to macrophages and foam cells)
      • Foam cells → Macrophages full of lipids
  • Factor release
    • Inflammation and cytokines
  • Smooth muscle cell proliferation
    • Extracellular matrix deposition
    • Migration of smooth muscle cells into intima
  • Lipid accumulation
    • Continued accumulation of lipids extracellularly and within macrophages and smooth muscle cells
    • Can rupture

Prinzmetal Angina

  • Coronary vasospasm
  • Major risk factor: Smoking
    • Seen in younger patients
  • Pain at rest occurring at night
  • Indistinguishable from classic angina
  • Diagnosed by coronary ateriography
  • Transient ST elevation with no sign of stenosis on arteriography
  • Calcium channel blockers → FIRST LINE. Diltiazem
    • Nitrates → Second line
  • Smoking cessation

Cytochrome P450

CYP450 Inhibitors

    • Ciprofloxacin
    • Ritonavir
    • Amiodarone
    • Cimetidine
    • Ketoconazole
    • Acute alcohol use
    • Macrolides
    • Isoniazid
    • Grapefruit Juice
    • Omeprazole
    • Sulfanamides

CYP450 Inducers

    • Phenytoin
    • Carbemazepine
    • Griseofulvin
    • Barbiturates
    • Rifampin
    • St John’s wart
    • Chronic alcoholism

Disulfiram Reaction

  • Inhibition of acetaldehyde dehydrogenase
    • Increase aldehyde
    • Flushing, sweating, nausea, headache, hypotension
  • Causes
    • Metronidazole
    • Certain cephalosporins
      • Cefotetan
      • Cefamandole
      • Cefoperazone
    • 1st gen sulphonylurea
      • Tolbutamide

Renin

  • Stimulated by Beta 1 receptors in kidney
  • Macula densa sense reduced sodium in glomerular filtrate
  • JG apparatus sensing low BP
  • Renin cleaves angiotensinogen into angiotensin 1
  • Angiotensin 1 becomes 2
    • Enzyme: ACE (Angiotensin converting enzyme)
    • Produced in the lungs and kidneys
  • Angiotensinogen produced by the liver

Angiotensin II

  • Vasoconstrictor
  • Stimulates aldosterone secretion
    • Causes sodium and water reabsorption

BNP

  • Causes vasodilation
  • Increased excretion of sodium and water in urine

Splitting

  • A2 P2 →Increased split during inspiration

Hand grip

  • Increases SVR and after load
  • Makes MR louder

Val salva

  • Decreases venous return
  • Reduces preload and afterload
  • Makes HOCM louder

Patent Ductus Arteriosis

  • Associated with rubella
  • Indomethacin closes it

Carbidopa

  • Inhibits Dopa decarboxylase
  • Prevents conversion from DOPA to dopamine

Heart Valve problems

Aortic stenosis

  • Ejection click
  • Crescendo decrescendo

Mitral regurgitation

  • Increased by hand grip and squatting

Mitral valve prolapse

  • Midsystolic click
  • Possible systolic crescendo murmur after click
  • Valsalva makes murmur start earlier

Mitral valve stenosis

  • Small pause in the beginning
    • Due to initial isovolumetric contraction
  • Opening snap
  • Heard in apex
    • In left lateral decubitus
      • S3, S4, MR heard better on left lateral decubitus
  • Caused by rheumatic heart disease
  • PCWP is higher than LV diastolic pressure
    • PCWP normally  < 12
    • LA pressure < 12
    • Left ventricular diastolic pressure – Around 10 mm Hg
    • Pressure in left atrium is higher → Increasing PCWP pressure

Aortic Regurgitation

  • Diastolic murmur
  • Immediately after S2
  • Left side of sternum
  • Wide pulse pressure
  • Water hammer pulse
  • Causes
    • Dilated aortic root → Syphillis
    • Marfan’s
    • Bicuspid aortic valve
      • Most commonly causes AS though
    • Rheumatic fever

Ventricular action potential:

  • Phase 0 → Increased sodium permeability
  • Phase 1→ Repolarization. In-activation of sodium channels. K+ channels begin to open
  • Phase 2 → Plataeu → K+ open, Ca2+ open
    • Causes calcium release from SR and myocyte contraction
  • Phase 3 → K+ permeability increased. Closing of calcium channels
    • K+ efflux causes repolarization
  • ERP
    • Cannot potentiate another action potential

Pacemaker Action Potential

  • Phase 0 → Voltage gated calcium channels open after reaching threshold
    • Not due to sodium such as in myocytes
  • Phase 3 → Increased potassium permeability
  • Phase 4 → Freely permeable to potassium. Gradual depolarization due to sodium channel conductance

Smooth ER makes steroids, lipids, phospholipids. Involved in detoxifying as well



Pretest probability of coronary artery disease


Typical chest pain Atypical chest pain Non-anginal chest pain Asymptomatic
Younger than 40 M 10-90% 10-90% 5-10% <5%
F 10-90% <5% <5% <5%
40-50 M 10-90% 10-90% 5-10%
F 10-90% 5-10% <5% <5%
50-60 M 5-10%
F 5-10% <5%
More than 60 M 5-10%
F 5-10%
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