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Block 3
Week 2
41
Biology
Graduate
02/26/2009

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Term
Describe the bilirubin cycle starting with old RBC’s.
Definition
RBC heme->turns to bilirubin by spleen or liver macrophages->unconjugated bilirubin-albumin travels blood to liver->liver conjugates with glucoronic acid to make soluble->bacteria in intestine convert it to urobilinogen->absorbed to enterohepatic cycle and bilirubin reused.
Term
What would be the causes of increased serum conjugated bilirubin levels versus unconjugated?
Definition
Unconjugated would be from hemolysis, Conjugated would be from bile duct blockage or caniculi damage; however, in liver disease both levels would be increased.
Term
In neonates jaundice is commonly due to physiological problems or blood type incompatibility, explain why these cause jaundice.
Definition
Physiological - liver not fully developed to conjugate bilirubin; Blood type- mother blood proteins incompatible with immune system of baby causing hemolysis
Term
What Is the disease called where a newborn has brain damage due to insoluble unconjuagted bilirubin accumulating in the brain?
Definition
Kernicterus
Term
Primary porphyrias is a hereditary disease of heme synthesis and secondary porphyries is a acquired(eg lead), but what is the difference between primary acute and cutaneous porphyries?
Definition
Acute is a defect in the early step of heme synthesis that creates too much ALA which is toxic to neurons causing GI problems and neuropsychiatric disorders, cutaneous is a defect in later steps which causes skin lesions, red urine/teeth, and anemia.
Term
Why is it that plasma levels of ferritin reflect cellular levels?
Definition
Because of leakage of ferritin into the plasma at a constant rate. Ferritin is the primary intracellular iron storage protein, without iron it is called apoferritin.
Term
Where is iron primarily stored?
Definition
Bone marrow, liver cells, macrophages
Term
What is the transport protein for iron?
Definition
Transferritin
Term
Which of these molecules utilize iron - hemoglobin, myoglobin, cytochromes, and non-heme iron proteins?
Definition
All of them
Term
What are the top 3 reasons for anemia due to abnormal iron metabolism?
Definition
Fe deficiency, defective storage, defective utilization in erythroblasts.
Term
In a person with defective iron storage causing anemia, what liver peptide binds to ferroportin causing it to degrade which inhibits iron export out of cells?
Definition
Hepcidin
Term
What is the hereditary disorder that causes abnormally high iron levels in plasma and tissues?
Definition
Hemochromatosis, causes excess Fe absorption damaging the liver, heart and pancreas; can also be caused by mutation in hepcidin gene
Term
True or False: Sideroblastic anemia is when iron accumulation in erythroblasts causes ferritin to precipitate, which can be inborn or acquired.
Definition
true
Term
Where is iron stored?
Definition
Enterocytes
Term
Ammonia is produced by the catabolism of what 3 things?
Definition
Amino acids, nucleotides, and catecholamines
Term
True or false: ammonia is highly toxic to the brain and is present predominantly as ammonium.
Definition
True
Term
In the urea cycle, what is the initial substrate, final substrate, and how many steps are there?
Definition
NH4, urea, 5
Term
Why does the deficiency of a urea cycle enzyme, like in hereditary hyperammonemia, cause elevated levels of ammonia even though some intermediates in the cycle can be cleared by the kidney?
Definition
Because the cycle will still slow down causing a surplus of ammonia based molecules in the cycle and will be rate-limited by kidney clearance.
Term
What are these three compounds used to treat - arginine, sodium benzoate, sodium phenylacetate?
Definition
Hyperammonemia, because they increase nitrogen excretion by allowing synthesis of excretable molecules in their respective cycles
Term
What organ metabolizes NH3 to urea and what percent of ammonia is excreted by the kidneys and colon?
Definition
Liver, 75, 25
Term
Why does hyperammonemia occur when you have liver disease such as cirrhosis, hepatitis, or biliary disease?
Definition
Decreased urea synthesis by hepatocytes, and development of shunts caused by portal hypertension that results in the NH3 being absorbed and not processed by the liver
Term
Ammonia is toxic because it poisons ion channels and pumps but how does it decrease ATP?
Definition
It depletes a-ketoglutarate which is a vital intermediate in the citric acid cycle
Term
Why does alcohol increase the activity level of other drugs?
Definition
The MEOS, microsomal ethanol oxidizing system, utilizes the same cytochrome P450 which normally metabolizes those drugs.
Term
As far as the causes of liver degeneration due to alcoholism which is a more important factor, malnutrition or the metabolism of alcohol?
Definition
The metabolism of alcohol adversely affects the metab of other carbs
Term
In the metabolism of alcohol which pathway is more important, alcohol dehydrogenase or acetaldehyde dehydrogenase?
Definition
Alcohol dehydro
Term
What are the 3 pathways of alcohol metabolism?
Definition
Alcohol dehydrogenase, MEOS, catalase reaction
Term
What is the difference between primary and secondary hemostasis in response to blood vessel damage?
Definition
Primary - constrict damaged vessels and form temporary seal of platelets, secondary - formation of a solid blood clot
Term
Briefly describe how a temporary seal by platelets forms.
Definition
Platelets bind to collagen in exposed subendothelium, causing them to form pseudopodia which enhances binding and interactions, and it also causes them to exocytose ADP and TXA2 to induce more platelets to bind
Term
What is the role of prostacyclin in blood aggregation?
Definition
It is released by normal endothelium and prevents blood clot formation
Term
What is the difference between a soft clot and a hard clot?
Definition
Soft is an aggregate of fibrin monomers (hydrolyzed fibrinogen via thrombin), a hard clot is when a covalent bond forms between those monomers forming crosslinks
Term
What is the difference in the initiation of the intrinsic and extrinsic pathways for coagulation?
Definition
Intrinsic is initiated by an abnormal surface, extrinsic begins due to the trauma-induced exposure of tissue factor which is on fibroblast membranes.
Term
List the steps of the final common pathway of coagulation between intrinsic and extrinsic.
Definition
X->V->Prothrombin->Thrombin->Fibrinogen->Fibrin->XIII->cross linked clot
Term
How does the thrombin-thrombomodulin complex limit clot formation?
Definition
They activate protein C and S which hydrolyze factors V and XIII
Term
What is the role of antithrombin and heparin in blood clotting?
Definition
Antithrobin binds to active clotting proteases and inhibits them, heparin augments that complex formation
Term
Some coagulation factors (II,VII,IX,X,C,S) need their glutamate residues to be modified to be able to bind to Ca and become active, which vitamin is required for this modification?
Definition
K
Term
Tissue Plasminogen Activator is secreted into the blood by vascular endothelial cells, what is its role in breaking down fibrin clots to D-Dimers?
Definition
TPA->Plasminogen->Plasmin->Fibrin split products called D-Dimers, which can be seen in thromboembolism, infection, and neoplasia
Term
The activity of what clotting pathway is measured with prothrombin time versus activated partial thromboplastin time?
Definition
PT measures extrinsic/final common pathway, APTT measures intrinsic/final common pathway
Term
True or false: both hemophilia A and B are X-linked recessive.
Definition
True
Term
True or false: acquired thrombophilia can be due to all of the following - infection, inflammation, cancer, antiphospholipid syndrome.
Definition
True
Term
True or false: If thrombophilia is widespread, it is called disseminated intravascular coagulation and it only causes thrombi.
Definition
False, the thrombi use all the platelets not leaving enough to form necessary clots and will lead to bleeding.
Term
Which of these situations indicates either hepatocellular damage or cholestatic disease - 1: high total bilirubin, high AST/ALT 2: high conjugated bilirubin, high alkaline phosphotase?
Definition
Liver=1, Gall bladder=2
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