Exam III Quan Study Guide Flashcards
Importance of oxygen
Oxygen is the life-giving, life-sustaining element. Approximately 90% of the body’s energy is created by oxygen. Nearly all of the body’s activities, from brain function to elimination, are regulated by oxygen.
Oxygen is —— at body temperature
inert
oxidation
Oxidation is gain of oxygen
Reduction
Reduction is loss of oxygen
What are the ROS
reactive oxygen species, oxidizes DNA, lipids, and proteins. They are molecules that are highly reactive, but small. They modulate activities of oxidized targets when they are controlled tightly. Reactive oxygen species is one of many cell-signaling processes.
What are the free radicals
Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons and can be formed when oxygen interacts with certain molecules. Once formed these highly reactive radicals can start a chain reaction, like dominoes
How are ROS formed
ROS are formed as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis.
Oxidative stress
an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants
How do ROS damage cells?
In aerobic organisms the energy needed to fuel biological functions is produced in the mitochondria via the electron transport chain. In addition to energy, reactive oxygen species (ROS) with the potential to cause cellular damage are produced. ROS can damage DNA, RNA, and proteins, which, in theory, contributes to the physiology of aging.
Physiological functions of ROS
(-)). In the cardiovascular system, besides playing a critical role in the development and progression of vasculopathies and other important pathologies such as congestive heart failure, atherosclerosis and thrombosis, ROS also regulate physiological processes.
have important roles in cell signaling and homeostasis.[
Markers of liver disease
These tests include prothrombin time (PT/INR), aPTT, albumin, bilirubin (direct and indirect), and others. Liver transaminases (AST or SGOT and ALT or SGPT) are useful biomarkers of liver injury in a patient with some degree of intact liver function.
Liver and glucose metabolism
Energy is required for the normal functioning of the organs in the body. Many tissues can also use fat or protein as an energy source but others, such as the brain and red blood cells, can only use glucose. Glucose is stored in the body as glycogen. The liver is an important storage site for glycogen.
Liver plasma proteins
Other plasma proteins produced by the liver include albumin which binds many water-insoluble substances and contributes to osmotic pressure, fibrogen which is key to the clotting process, and certain globulins which transport substances such as cholesterol and iron.
Acute phase protein
Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute-phase response). Inflammatory cells and red blood cells.
What is heme?
an iron-containing compound of the porphyrin class that forms the nonprotein part of hemoglobin and some other biological molecules.
The rate limiting step in heme synthesis
ALA Synthase is the committed step of the heme synthesis pathway, & is usually rate-limiting for the overall pathway. Heme functions as a feedback inhibitor, repressing transcription of the ALA Synthase gene in most cells.
Heme controls its own synthesis
At which step do you regulate heme synthesis?–
First step δ-ALA synthase and heme controls its own production
What is bilirubin
an orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile.
What is Jaundice?
a yellowish or greenish pigmentation of the skin and whites of the eyes due to high bilirubin levels
Three main causes of jaundice
Pre-hepatic jaundice
Pre-hepatic jaundice occurs when a condition or infection speeds up the breakdown of red blood cells. This causes bilirubin levels in the blood to increase, triggering jaundice.
Causes of pre-hepatic jaundice include:
malaria – a blood-borne infection spread by mosquitoes sickle cell anaemia – an inherited blood disorder where the red blood cells develop abnormally; it's most common among black Caribbean, black African and black British people thalassaemia – similar to sickle cell; it's most common in people of Mediterranean, Middle Eastern and, in particular, South Asian descent Crigler-Najjar syndrome – a genetic syndrome where an enzyme needed to help move bilirubin out of the blood and into the liver is missing hereditary spherocytosis – a genetic condition that causes red blood cells to have a much shorter life span than normal
Intra-hepatic jaundice
Intra-hepatic jaundice happens when a problem in the liver – for example, damage due to infection or alcohol, disrupts the liver’s ability to process bilirubin.
Causes of intra-hepatic jaundice include:
the viral hepatitis group of infections – hepatitis A, hepatitis B and hepatitis C alcoholic liver disease – where the liver is damaged as a result of drinking too much alcohol leptospirosis – a bacterial infection that's spread by animals, particularly rats glandular fever – a viral infection caused by the Epstein-Barr virus drug misuse – leading causes are ecstasy and overdoses of paracetamol primary biliary cirrhosis – a rare condition that causes progressive liver damage Gilbert's syndrome – a common genetic syndrome where the liver has problems breaking down bilirubin at a normal rate liver cancer – a rare and usually incurable cancer that develops inside the liver exposure to substances known to be harmful to the liver – such as phenol (used in the manufacture of plastic) or carbon tetrachloride (widely used in the past in processes such as refrigeration, although now its use is strictly controlled) autoimmune hepatitis – a rare condition where the immune system starts to attack the liver primary sclerosing cholangitis – a rare type of liver disease that causes long-lasting (chronic) inflammation of the liver Dubin-Johnson syndrome – a rare genetic syndrome where the liver is unable to move bilirubin out of the liver
Post-hepatic jaundice
Post-hepatic jaundice is triggered when the bile duct system is damaged, inflamed or obstructed, which results in the gallbladder being unable to move bile into the digestive system.
Causes of post-hepatic jaundice include:
gallstones – obstructing the bile duct system pancreatic cancer gallbladder cancer or bile duct cancer pancreatitis – inflammation of the pancreas, which can either be acute pancreatitis (lasting for a few days) or chronic pancreatitis (lasting for many years)
Some causes of jaundice are common, such as hepatitis and gallstones, whereas other causes, such as Crigler-Najjar syndrome and Dubin-Johnson syndrome, are much rarer.
Drug metabolism in the liver
The liver is the principal site of drug metabolism. Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active—sometimes even more so than the parent compound. An inactive or weakly active substance that has an active metabolite is called a prodrug, especially if designed to deliver the active moiety more effectively.
Drugs can be metabolized by oxidation, reduction, hydrolysis, hydration, conjugation, condensation, or isomerization; whatever the process, the goal is to make the drug easier to excrete. The enzymes involved in metabolism are present in many tissues but generally are more concentrated in the liver. Drug metabolism rates vary among patients. Some patients metabolize a drug so rapidly that therapeutically effective blood and tissue concentrations are not reached; in others, metabolism may be so slow that usual doses have toxic effects. Individual drug metabolism rates are influenced by genetic factors, coexisting disorders (particularly chronic liver disorders and advanced heart failure), and drug interactions (especially those involving induction or inhibition of metabolism).
For many drugs, metabolism occurs in 2 phases. Phase I reactions involve formation of a new or modified functional group or cleavage (oxidation, reduction, hydrolysis); these reactions are nonsynthetic. Phase II reactions involve conjugation with an endogenous substance (eg, glucuronic acid, sulfate, glycine); these reactions are synthetic. Metabolites formed in synthetic reactions are more polar and thus more readily excreted by the kidneys (in urine) and the liver (in bile) than those formed in nonsynthetic reactions. Some drugs undergo only phase I or phase II reactions; thus, phase numbers reflect functional rather than sequential classification.
Cytochrome P-450
are proteins of the superfamily containing heme as a cofactor and, therefore, are hemoproteins.
CYPs are the major enzymes involved in drug metabolism, accounting for about 75% of the total metabolism.[16] Most drugs undergo deactivation by CYPs, either directly or by facilitated excretion from the body. Also, many substances are bioactivated by CYPs to form their active compounds
