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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" | |||
|+ | |||
|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 | |||
{| class="wikitable" | |||
|+ | |||
! | |||
!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: | |||
{| class="wikitable" | |||
|+ | |||
! | |||
! | |||
! | |||
! | |||
! | |||
|- | |- | ||
|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 | |||
<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 | |||
* 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 | |||
<br /> | |||
== Pretest probability of coronary artery disease == | |||
<br /> | |||
{| class="wikitable" | |||
|+ | |||
! | |||
! | |||
!Typical chest pain | |||
!Atypical chest pain | |||
!Non-anginal chest pain | |||
!Asymptomatic | |||
|- | |- | ||
| rowspan="2" |Younger than 40 | |||
| - | |M | ||
| - | |10-90% | ||
| | |10-90% | ||
| | |5-10% | ||
| | |<5% | ||
| | |- | ||
| - | |F | ||
| | |10-90% | ||
|<5% | |||
|<5% | |||
|<5% | |||
|- | |- | ||
| rowspan="2" |40-50 | |||
|M | |||
| | |||
| | | | ||
| - | |10-90% | ||
| | |10-90% | ||
|5-10% | |||
| | |||
|- | |- | ||
|F | |||
|10-90% | |||
|5-10% | |||
|<5% | |||
|<5% | |||
| | |||
| | |||
| | |||
| | |||
|- | |- | ||
| rowspan="2" |50-60 | |||
|M | |||
| | | | ||
| | | | ||
| | | | ||
|5-10% | |||
|- | |||
|F | |||
| | | | ||
| | | | ||
|5-10% | |||
|<5% | |||
|- | |- | ||
| rowspan="2" |More than 60 | |||
|M | |||
| | | | ||
| | | | ||
| | | | ||
|5-10% | |||
|- | |||
|F | |||
| | | | ||
| | | | ||
|- | | | ||
|5-10% | |||
|} | |} | ||
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 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)
- IF1, IF2, If3
- 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.
- Stop codons
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
- Phosphorylates FBP2/PFK2 complex → Activating FBP2 and inactivating PFK2
- 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
- Migration of monocytes into intima (Transformed to macrophages and foam cells)
- 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
- In 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% |