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Wednesday, September 27, 2017
Tuesday, September 26, 2017
Pathology Review
Requested by Krishna! Here are my review powerpoints for Dr. Plummer's lectures! ^.^
Types of Diseases
Necrosis
Inflammation
Tissue Repair
Tumors
Atherosclerosis
Myocardial Infarction
Types of Diseases
Necrosis
Inflammation
Tissue Repair
Tumors
Atherosclerosis
Myocardial Infarction
Monday, September 25, 2017
Saturday, September 23, 2017
Dyslipidemia
Statin Therapy
ASCVD
LDL > 190
age 40 to 75, DM, LDL 70 to 189
age 40 to 75, 10 year risk ASCVD > or = 7.5%
Thursday, September 21, 2017
Bile Salt Synthesis
Dietary lipids have low solubility. Bile salts act as detergents to emulsify them. Bile salts are synthesized in the liver and stored in the gallbladder. They are reabsorbed in the GI tract and transported back into the liver via enterohepatic circulation.
Cholesterol is modified via hydroxylation and carboxylation to increase solubility. 7 alpha hydroxylase is the rate limiting step. Cholic acid and chenodeoxycholic acid are primary bile acids. In the intestine, they are converted into deoxycholic and lithocholic acid via bacterial enzymes. These secondary acids are less soluble and so are easily excreted.
Bile salts can also be conjugated to glycine or taurine, lowering the pKa and making the bile salts better detergents.
Cholesterol is modified via hydroxylation and carboxylation to increase solubility. 7 alpha hydroxylase is the rate limiting step. Cholic acid and chenodeoxycholic acid are primary bile acids. In the intestine, they are converted into deoxycholic and lithocholic acid via bacterial enzymes. These secondary acids are less soluble and so are easily excreted.
Bile salts can also be conjugated to glycine or taurine, lowering the pKa and making the bile salts better detergents.
Cholesterol Biosynthesis
Citrate transport system moves acetyl CoA from mitochondria into cytoplasm. Thiolase, HMG CoA synthase, and HMG CoA reductase (rate-limiting) convert it into mevalonate. Mevalonate is then converted into IPP and then cholesterol.
Cholesterol can be esterified and stored in the cell via ACAT, or it can be secreted as a lipoprotein and then converted via LCAT.
Transcriptional Control
If there is a high level of cholesterol, it binds to SCAP and inactivates it. If there is low cholesterol, then SCAP is active. SCAP-SREBP can be transported into the Golgi, where the proteases cleave off the DNA binding domain. That DNA binding domain goes into the nucleus and interacts with SRE. SREBP can then activate the genes for HMG CoA reductase synthesis.
Post-transcriptional control includes proteolysis of the reductase or degradation of the HMG CoA reductase mRNA.
Phosphorylation
Glucagon --> phosphorylation of HMG CoA reductase via kinase like AMPK --> decrease cholesterol synthesis
Insulin --> dephosphorylation of HMG CoA reductase via phosphatase --> increase cholesterol synthesis
Cholesterol can be esterified and stored in the cell via ACAT, or it can be secreted as a lipoprotein and then converted via LCAT.
Transcriptional Control
If there is a high level of cholesterol, it binds to SCAP and inactivates it. If there is low cholesterol, then SCAP is active. SCAP-SREBP can be transported into the Golgi, where the proteases cleave off the DNA binding domain. That DNA binding domain goes into the nucleus and interacts with SRE. SREBP can then activate the genes for HMG CoA reductase synthesis.
Post-transcriptional control includes proteolysis of the reductase or degradation of the HMG CoA reductase mRNA.
Phosphorylation
Glucagon --> phosphorylation of HMG CoA reductase via kinase like AMPK --> decrease cholesterol synthesis
Insulin --> dephosphorylation of HMG CoA reductase via phosphatase --> increase cholesterol synthesis
Monday, September 18, 2017
2,3-BPG
2,3 BPG is produced by erythrocytes when there are low levels of oxygen, like at high altitudes. 2,3 BPG shifts the oxygen dissociation curve to the right so that hemoglobin has reduced affinity for oxygen. This results in an increased in O2 delivery to the tissues.
1,3 BPG, the precursor to 2,3 BPG, is formed during one of the steps in glycolysis. In hypoxic environments, it does not become pyruvate but instead is converted into 2,3 BPG by BPG mutase. As a result, the cell is sacrificing the formation of ATP for increased O2 delivery.
1,3 BPG, the precursor to 2,3 BPG, is formed during one of the steps in glycolysis. In hypoxic environments, it does not become pyruvate but instead is converted into 2,3 BPG by BPG mutase. As a result, the cell is sacrificing the formation of ATP for increased O2 delivery.
Monday, September 11, 2017
Chiari I and II Malformations
Chiari I malformation is when the lower part of the cerebellum extends into the foramen magnum. Type I may not cause any symptoms. In fact, it may not detected until much later in life.
Chiari II malformation (Arnold-Chiari malformation) is the herniation of the cerebellar vermis and brain stem through the foramen magnum. The herniation can then cause hydrocephalus. Type II is associated with myelomeningocele. During antenatal care, an ultrasound may show a lemon or banana sign. Infants may display symptoms such as stridor (sounds like a seal), dysphagia, hypotonia, and ataxia.
https://rarediseases.info.nih.gov/diseases/9232/chiari-malformation-type-2
https://radiopaedia.org/articles/chiari-ii-malformation
Chiari II malformation (Arnold-Chiari malformation) is the herniation of the cerebellar vermis and brain stem through the foramen magnum. The herniation can then cause hydrocephalus. Type II is associated with myelomeningocele. During antenatal care, an ultrasound may show a lemon or banana sign. Infants may display symptoms such as stridor (sounds like a seal), dysphagia, hypotonia, and ataxia.
https://rarediseases.info.nih.gov/diseases/9232/chiari-malformation-type-2
https://radiopaedia.org/articles/chiari-ii-malformation
Thursday, September 7, 2017
Wednesday, September 6, 2017
Wigger's Diagram
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