Lecture 25

Question 1

Alpha and Beta _____ and _____ are proteins on the _____ side of RBC membranes that help form the cytoskeleton. Mutations in the genes for these proteins can cause hereditary _______.

Answer 1

Spectrin

Ankyrin

Inner

Hereditary Spherocytosis

Question 2

Based on the respective intra vs extracellular concentrations of K+, Na+, and Ca++, an increase in the plasma concentration of which ion would be indicative of hemolysis.

Answer 2

Intracellular [K+] is higher than extracellular, so you would see and INCREASE in plasma K+.

[Na+] and Ca++] are normally low, so you wouldn’t really observe a measurable change in plasma concentrations bc of hemolysis.

Question 3

Methemoglobin (unable to bind O2) results from the ______ (+3) state of iron in the Hb molecule. The ______ (+2+) state binds O2.

Answer 3

Ferric

Ferrous

Question 4

RBC metabolism depends on _______ glycolysis for ATP production.

Answer 4

Anaerobic glycolysis

Question 5

The pentose phosphate pathway (aka Hexose monophosphate shunt) is important in detoxifying oxidizing agents. _____ dehydrogenase is an important component in this pathway –> deficiencies can lead to the denaturing of Hb and anemia.

Answer 5

G6P dehydrogenase (G6PD)

Question 6

An increase in _________ (oxidized Hb) manifests as cyanosis. The _______ reductase pathway reduces this molecule back to the reduced form of Hb (which oxidation state of iron is in reduced Hb?)

Answer 6

Methemoglobin

Methemoglobin

Ferrous (2+)

Question 7

The ____-_____ pathway generates 2,3-BPG –> right shift to the Oxyhemoglobin dissociation curve.

Answer 7

Rapoport-Luebering Pathway

Question 8

RBCs of a fetus up to 6 months gestation will exhibit about 90% Hb__ and about 10% Hb__. At birth, the values are about 60-90% Hb__, 10-40% Hb__, and <2% Hb__. From 2 years of age through adulthood, the mojority of Hb (greater than 95%) is Hb__, with < 2% Hb__, and < 3.5% Hb__.

Answer 8

HbF

HbA

HbF

HbA

HbA2

HbA

HbF

HbA2

Question 9

Extravascular hemolysis and heme degradation is mediated by ______. Intravascular hemolysis (fragmentation hemolysis) requires Hb to bind to ______ and/or hemopexin. Which one of these brings hemoglobin to Macrophages and which one brings it to Hepatocytes?

Answer 9

Macrophages

Haptoglobin

If there’s not enough Haptoglobin, which transports Hemoglobin to macrophages, then it will bind Hemopexin and be transported to hepatocytes.

Question 10

If the capacity of the blood to bind and transport heme is depleted (so depleted haptoglobin and hemopexin), heme goes to the ______. How can you tell this is happening?

Answer 10

Kidneys

Tea or Root beer colored-urine indicates this is happening

Question 11

There will be an increase in free plasma hemoglobin in the case of _______ hemolysis but not ______ hemolysis. There will also be urine hemoglobin and urine hemosiderin present for ________ hemolysis but not ______ hemolysis.

Answer 11

Intravascular

Extravascular

Intravascular

Extravascular

Question 12

______ is the protein that transports iron. It comes in two forms. The first, ______, typically has one or two iron atoms bound. The second, ______, does not have iron bound. The _______ receptor is on all cell surfaces (more so on RBC progenitors and hepatocytes). This receptor determines the amount of iron entering a cell.

Answer 12

Transferrin

Transferrin

Apotransferrin

Transferrin receptor

Question 13

_____ is the protein used to store iron in cells. It’s mostly found in RBCs, BM macrophages, and hepatocytes. Keep in mind this protein is involved in the acute phase inflammatory response. Think about what this means for using serum ferritin as an estimate of storage iron.

Answer 13

Ferritin

Question 14

Iron can be consumed in the ferrous heme state from animal products (meat) or in the ferric state from plants. The heme iron is absorbed into enterocytes via the heme transporter, while the ferric plant iron is converted to ferrous and absorbed via ____1. Iron in the enterocytes is either stored/shed as ______ or transported to the blood via ________. This transporter can be blocked by ______ when the body has sufficient iron OR during inflammation. Keep in mind ferrous iron is converted to ferric iron for transport via _______ and apo______.

Answer 14

DMT1

Ferritin

Ferroportin

Hepcidin

Transferrin

Apotransferrin

Question 15

There are three stages of Hemostasis. Primary hemostasis involves blood vessels, ______ that for the primary thrombus, and von Willebrand factor.

Secondary hemostasis involves coagulation proteins that form a ______ clot to stabilize the primary thrombus.

Lastly, Fibrinolysis requires ______ to digest the fibrin clot when it is no longer needed.

Answer 15

Platelets

Fibrin clot

Plasmin

Question 16

von Willebrand factor is what allows platelets to bind to exposed sudothelium _____ at the site of an injury (Adhesion). It bind specifically to GP Ib-IX-V. von Willebrand factor (VWF) is very large and is synthesized by endothelial cells and _______ (cells that produce platelets). When it is cleaved into the active monomer by ______13 (inhibition of this factor leads to TTP), it can bind the platelet to the sudothelium and also binds factor ____, another factor necessary for thrombus formation.

Answer 16

Collagen

Megakaryocytes

ADAMTS13

Factor VIII

Question 17

Platelet activation requires receptor GP IIb-IIIa. Deficiency in this receptor leads to _______ thrombasthenia.

Answer 17

Glanzmann thrombasthenia

Question 18

Thromboxane A production requires ______, which is irreversibly acetylated and inhibited by Apirin.

Answer 18

Cyclooxygenase

Question 19

________ and VWF form bridges between GP IIb-IIIa to hold platelets together (Aggregation).

Answer 19

Fibrinogen

Question 20

Coagulation factors are synthesized in the _____. Which factors are Vit K dependent?

Answer 20

Liver

Factors II, VII, IX, and X

Question 21

Hemophelia A or B results typically in males bc of a deficiency in Factor VIII (which circulates in complex with VWF) and IX. Why might males be most often affected (think inheritance)?

Answer 21

These are X-linked deficiencies, so males will be affected more often.

Question 22

______ is a serine protease that inhibits thrombin (factor IIa). When thrombin is bound to ______, this inhibition is INCREASED.

Answer 22

Antithrombin

Heparin

Question 23

Activated Protein C and Protein S inactivate factors ___a and ___a.

Answer 23

Va

VIIIa

Question 24

TPA acts on _______, generating the active form ______. This is what breaks down fibrin into degradation products or breaks down Cross-linked fibrin to form ___-dimers.

Answer 24

Plasminogen

Plasmin

D-dimers