Plasma Flashcards
Four components of blood
- Red blood cells
- White blood cells
- Platelets
- Plasma
Plasma makes up about _ % of blood
Plasma makes up about 55% of blood
* The remaining 45% consists of cellular components
What substances make up the blood plasma?
Water, proteins, solutes
Why is it important that the plasma has a high water content?
- Encourages smooth blood flow
- Decreases the blood’s viscosity
- Important in maintaining blood pressure and electrolyte balance
Three proteins found in plasma
- Albumin
- Immunoglobulins
- Fibrinogens
The key regulator of blood osmolality is _
The key regulator of blood osmolality is albumin
Two key differences btwn plasma and serum
- Only plasma has clotting factors; serum does not have fibrinogen
- Serum makes up a smaller percentage of the blood
Plasma transfusions
Plasma transfusions involve separating the plasma from donated blood and freezing it (fresh frozen plasma)
* Can be given as a transfusion to people in trauma or serious accidents who may experience a lot of bleeding
Plasma fractionation
Plasma fractionation is where important components of plasma are separated out (albumin, fibrinogen, immunoglobulins)
* Albumin –> patient with ascites
* Fibrinogen –> patient with hemophilia
* Ig –> patient with immune deficiency
Plasma exchange
Plasma exchange involves a machine that withdraws blood, separates out the plasma, and replaces it with a substitute and pumps it back into the patient
Erythrocyte structure maximizes the available volume for hemoglobin; they lack _ and _
Erythrocyte structure maximizes the available volume for hemoglobin; they lack organelles and nuclei
* Imagine them as a hemoglobin-rich cytoplasm enclosed in a plasma membrane
Why do RBCs have a disc-like shape with central depression?
RBCs must maneuver through capillaries and squeeze through small spaces like gaps between endothelial cells in splenic sinusoids –> its shape gives it flexibility
RBC’s have an approximate diameter of _ um
RBC’s have an approximate diameter of 7.8 um
Explain how the shape of RBCs in sickle cell patients can cause pain crisis
Hemoglobin S forms a stiff rod inside the RBCs –> gives the cells a crescent/ sickle shape –> they are not flexible –> accumulate in small blood vessels –> block flow of blood –> downstream tissues don’t get oxygen –> pain crisis
Hereditary spherocytosis causes RBCs to _ , leading to _ and frequent _
Hereditary spherocytosis causes RBCs to have a spherical shape , leading to cytoskeletal instabilities and frequent hemolysis –> hemolytic anemia
Spectrin, actin, and ankyrin are important proteins for _
Spectrin, actin, and ankyrin are important proteins for maintaining the biconcave shape of RBCs
* ankyrin anchors the lattice-like structural network to the plasma membrane
Hemoglobin is a complex molecule with _ heme groups and _ globin chains
Hemoglobin is a complex molecule with 4 heme groups and 4 globin chains
Each heme group consists of _ ring with _ in its center attached by _ bonds
Each heme group consists of protoporphyrin ring with iron in its center attached by nitrogen bonds
What is the role of the iron molecules in hemoglobin?
Iron reversibly binds oxygen and carbon dioxide
Each heme group is surrounded by a _
Each heme group is surrounded by a globin chain (alpha, beta, delta, gamma)
* They appear in pairs
Adult hemoglobin has two alpha chains and two _ chains
Adult hemoglobin has two alpha chains and two beta chains
* Adult hemoglobin is also called hemoglobin A
Fetal hemoglobin has two alpha chains and two _ chains
Fetal hemoglobin has two alpha chains and two gamma chains
* Fetal hemoglobin is also called hemoglobin F
_ hemoglobin has the stronger affinity for oxygen
Hemoglobin F has the stronger affinity for oxygen
So that the fetus can extract oxygen from the mother’s bloodstream
The switch from hemoglobin F to hemoglobin A occurs at around _ months of age
The switch from hemoglobin F to hemoglobin A occurs at around 6 months of age
* Gamma production never totally ceases but the function in adults is unknown
_ is a congenital disorder of RBCs resulting from mutations in RBC cytoskeletal proteins and proteins that attach the cytoskeleton to the cell membrane
Hereditary spherocytosis is a congenital disorder of RBCs resulting from mutations in RBC cytoskeletal proteins and proteins that attach the cytoskeleton to the cell membrane
* Mutations in spectrin and ankyrin make the membrane cytoskeleton unstable –> RBCs are more prone to lyse
Red blood cells produce energy via _
Red blood cells produce energy via anaerobic glycolysis
* This process produces lactic acid as well
Two important side pathways of anaerobic glycolysis are _ and _
Two important side pathways of anaerobic glycolysis are pentose phosphate pathway and 2,3-BPG
The important product of PPP to RBCs is _ which can _
The important product of PPP to RBCs is NADPH which can reduce glutathione and protect membranes against oxidative stress
* Patients with G6PD deficiencies are prone to RBC damage and hemolysis
1,3-BPG –> 2,3-BPG via _ enzyme
1,3-BPG –> 2,3-BPG via bisphosphoglycerate mutase
In the RBC, 2-3-BPG stabilizes the _ form of hemoglobin
In the RBC, 2-3-BPG stabilizes the T state form of hemoglobin
* T state has a lower affinity for oxygen
* Causes a rightward shift
Explain the presence of 2,3-BPG in tissues where we need unloading to occur vs loading
- More 2,3-BPG is formed in the tissues to help release O2 from hemoglobin; waste products like H+ ions and CO2 also provokes O2 unloading
- Less 2,3-BPG is produced in the lungs to help attract more O2 to hemoglobin (loading)
The _ component of heme must be ingested through food; the _ component of heme must be synthesized in the body
The iron component of heme must be ingested through food; the protoporphyrin component of heme must be synthesized in the body
The first enzyme of heme synthesis is _ which requires _ as a cofactor
The first enzyme of heme synthesis is ALA synthase which requires vitamin B6 (pyridoxine) as a cofactor
A deficiency in B6 can lead to _ anemia
A deficiency in B6 can lead to sideroblastic anemia
* The anti-TB drug isoniazid is known to cause this –> presents as peripheral neuropathy
RBCs only live for about _ days after that we undergo heme catabolism in which hemoglobin is broken into heme + globin components
RBCs only live for about 120 days after that we undergo heme catabolism in which hemoglobin is broken into heme + globin components
What are the 6 main steps of heme catabolism
- Heme is broken down into bilirubin
- Unconjugated bilirubin is transported to the liver
- Bilirubin gets conjugated in the liver
- It is converted into urobilinogen
- Urobilinogen gets either reabsorbed or excreted as stercobilin
- Excreted in bile (stercobilin) or urine (urobilin)
Senescent RBCs get broken down by _ in the spleen via _
Senescent RBCs get broken down by macrophages in the spleen via heme oxygenase
Unconjugated bilirubin is lipid (soluble/ insoluble)
Unconjugated bilirubin is lipid soluble and insoluble in aqueous solutions –> must be bound to albumin to be transported throughout the blood
Unconjugated bilirubin gets transported to the _ to get conjugated
Unconjugated bilirubin gets transported to the liver to get conjugated
* It gets taken up into hepatocytes at their sinusoidal surface either passively or actively
Bilirubin is conjugated by the enzyme _ to become a water-soluble form
Bilirubin is conjugated by the enzyme UDP-glucuronyl-transferase (UGT1A1) to become a water-soluble form
After bilirubin is conjugated in the liver it next gets transported to _
After bilirubin is conjugated in the liver it next gets transported through the bile canalicular system or ureters
* It can now dissolve in bile, urine, and blood and will no longer diffuse to the tissues
Conjugated bilirubin in the bile ducts then moves to the intestine where the enzyme _ hydrolyzes glucuronic acid to reform unconjugated bilirubin
Conjugated bilirubin in the bile ducts then moves to the intestine where the enzyme beta-glucuronidase hydrolyzes glucuronic acid to reform unconjugated bilirubin –> then bilirubin gets converted into urobilinogen
Urobilinogen either gets reabsorbed and sent back to the liver or it gets converted into _ in the stool
Urobilinogen either gets reabsorbed and sent back to the liver; “enterohepatic circulation” or it gets converted into stercobilin in the stool
Bilirubin must get converted into _ to be excreted in the urine
Bilirubin must get converted into urobilin to be excreted in the urine
Usually unconjugated hyperbilirubinemia is caused by either _ or _
Usually unconjugated hyperbilirubinemia is caused by either increased breakdown of RBCs or decreased conjugation of bilirubin
Examples of increased RBC breakdown:
- G6PD deficiency
- Hereditary spherocytosis
- Hemolytic disease of newborn
Examples of decreased conjugation of bilirubin:
- Gilbert syndrome
- Crigler-Najjar syndrome
- Gray baby syndrome
_ is a decreased activity of UPD-glucuronyl-transferase on exertion
Gilbert syndrome is a decreased activity of UPD-glucuronyl-transferase on exertion
What is the clinical presentation of unconjugated hyperbilirubinemia?
- Jaundice
- Scleral icterus
- Dorsum of the tongue yellows
Neonates who have unconjugated hyperbilirubinemia are at risk of _
Neonates who have unconjugated hyperbilirubinemia are at risk of kernicterus
Usually conjugated hyperbilirubinemia is caused by either _ or _
Usually conjugated hyperbilirubinemia is caused by either deficiency of the canalicular membrane transporter or impaired bile flow
A deficiency of the canalicular membrane transporter blocks conjugated bilirubin from being able to move from the liver to the bile; this can cause _ and _ syndrome
A deficiency of the canalicular membrane transporter blocks conjugated bilirubin from being able to move from the liver to the bile; this can cause Dubin-Johnson syndrome and Rotor syndrome
* Causes: choledocolithiasis, tumors, parasite
What are the clinical manifestations of conjugated hyperbilirubinemia
- Dark urine
- Pale stools
- Scleral icterus (some unconjugated hyperbilirubinemia)
The reduced form of iron is called _ (Fe2+)
The reduced form of iron is called ferrous iron (Fe2+)
* Main dietary source is meat
The oxidized form of iron is called _ (Fe3+)
The oxidized form of iron is called ferric iron (Fe3+)
* Main dietary source is vegetables
Ferrous iron is bound to _ and therefore directly get absorbed by enterocytes of the duodenum via _
Ferrous iron is bound to heme and therefore directly get absorbed by enterocytes of the duodenum via heme carrier protein 1 (HCP1)
Non-heme bound ferric iron must first get reduced to ferrous iron via _ enzyme at the intestinal brush boarder; then it gets tranported into the enterocyte via _
Non-heme bound ferric iron must first get reduced to ferrous iron via ferrireductase enzyme at the intestinal brush boarder; then it gets tranported into the enterocyte via divalent metal transporter 1 (DMT1)
HCP1 transports _ iron
HCP1 transports heme-bound ferrous iron
DMT1 transports _ iron
DMT1 transports ferric iron that has been reduced to ferrous iron
Inside the enterocyte, iron remains bound to _
Inside the enterocyte, iron remains bound to ferritin –> “storage iron”
* Neutralizes iron’s free radicals to avoid cell damage
* This is why ferritin levels rise in inflammatory disease
_ is a transporter that transports iron across the cell membrane and into the bloodstream
Ferroportin is a transporter that transports iron across the cell membrane and into the bloodstream
_ is secreted by liver cells and it prevents iron from entering the blood by reducing ferroportin
Hepcidin is secreted by liver cells and it prevents iron from entering the blood by reducing ferroportin
* So hepcidin keeps the iron stored as ferritin
How do we overcome hepcidin when we need more iron?
Erythropoietin stimulates the bone marrow to make more RBCs & inhibits hepcidin production –> now more iron can be transported via the bloodstream via ferroportin
_ is a form of systemic iron overload where a mutation in HFE gene leads to mutant hepcidin which can’t down-regulate ferroportin
Hereditary hemochromatosis is a form of systemic iron overload where a mutation in HFE gene leads to mutant hepcidin which can’t down-regulate ferroportin
* Iron deposits in tissues –> diseases of heart, liver, pancreas, skin
Only _ form of iron can be bound to the protein transferrin for transport in the bloodstream
Only ferric iron can be bound to the protein transferrin for transport in the bloodstream
* Therefore ferrous iron –> ferric iron via hephaestin (enterocyte) and ceruloplasmin (liver)
Liver, spleen, and erythroid precursor cells are especially rich in _ receptors –>
Liver, spleen, and erythroid precursor cells are especially rich in transferrin receptors –> transferrin proteins bind these and get taken in via endocytosis
* Inside the cell the iron is stored as ferritin
* The liver stores the bulk of the iron
During inflammation, cytokines increase _ levels to keep iron from being released into the blood; why?
During inflammation, cytokines increase hepcidin levels to keep iron from being released into the blood
* We want to hide iron from scavenging bacteria
* However, this can lead to anemia of chronic diseases
