Bicarbonate Buffer System

What is the main purpose of the bicarbonate buffer system?

• Transport oxygen to tissues and remove CO2

• Nutrients in wastes out

Bicarbonate buffer system is dependent on:

• depends on concentration gradient

• CO2 is converted to bicarbonate transported through blood to alveoli and then diffuses back through the RBC, converted back to CO2 and then diffuses into lungs to be released

CO2 transport by RBC and plasma:

• 85 % HCO3 (bicarbonate)

• 10 % dissolved

• 5 % Carbaminohemoglobin

• CO2 is a biproduct/waste product

Passive process:

• Diffusion doesn’t require ATP but requires a concentration gradient

• Takes oxygen to tissues

CO2 transport by RBC and plasma steps:

1) CO2 is produced from cell membrane

2) CO2 diffuses into RBC

3) CO2 & H2O with help of carbonic annahydrase form carbonic acid

4) carbonic annahydrase dissociates into HCO3 & HCO3- and H+ binds to hemoglobin

5) HCO3- leaves RBC and a chloride shift into RBC to balance charge. HCO3- bicarbonate travels into the plasma.

RBC senescence and Hemolysis:

• RBC senescence = aging

• 120 day lifespan (iron will travel in hemoglobin; iron will be Recycled into new RBC)

• Recycling of Fe and amino acids (protoporphyrin ring is excreted as waste and not recycled)

• 1% of old RBC (also looses oxygen carrying capacity) taken out by fixed macrophages known as Reticuloendothelial system (RES) or mononuclear phagocyte system (MPS)

Extravascular:

• Majority of lysis (90%)

• Hemolysis happens in spleen part of RES

• Littoral cells reside in spleen and are macrophages

• Outside of peripheral blood vessel; RES reside primarily in the spleen (inside we have red purple which is the breakdown of RBC’s) and are macrophages

• RBC (7-8 micrometers) has to travel through the cynacoid cavity (2-4 micrometers) to make it to the spleen.

• Bilirubin is photosensitive

What are the main ways that littoral cells recognize RBC abnormalities?

• lack of deformability and elasticity

Intravascular:

• hemolysis occurs within the peripheral blood vessel; hemoglobin release into lumen of vessel

• Hemolysis affects certain proteins but still excrete protoporphyrin ring in waste

Extravascular hemolysis:

• Littoral cells detect changes in membrane and membrane proteins (will have an affect on elasticity and deformability

• Hemoglobin breakdown

• Can’t recycle protoporphyrin ring

• Bilirubin comes from breakdown of protoporphyrin ring

• Albumin is a protein carrier

Extravascular hemolysis steps (w/in peripheral blood and spleen):

1) Macrophages (littoral cells) breakdown Hb into Fe (transported by transferrin + bone marrow), and amino acids, sent to the amino acid pool. (Spleen → Extravascular hemolysis)

2) protoporphyrin ring gets broken down into bilirubin (jaundice)

3) bilirubin is picked up by albumin and taken into liver

4) bilirubin is converted into urobilinogen, further broken down in small intestine and eventually excreted as waste via large intestine

Intravascular hemolysis:

• no spleen involved

• Hepatocyte (cell w/in the liver)

• 5-10% hemolysis Intravascular

• Haptoglobin binds hemoglobin complex to prevent renal excretion

• Filtered through kidneys and reabsorbed. Renal tubular reabsorption maximum = 5g/day hemoglobin

• After it appears in urine

What is the difference between hemoglobinemia and Hemoglobinurea?

• hemoglobinemia: hemoglobin inside of blood

• Hemoglobinurea: hemoglobin inside of urine

Intravascular Hemolysis steps:

1) RBC ruptures in peripheral blood, haptoglobin forms a complex with hemoglobin

2) haptoglobin- hemoglobin complex is taken to the liver; Fe is recycled and transported by transferrin to bone marrow and amino acid are recycled and sent to the amino acid pool

3) protoporphyrin ring converted bilirubin inside of hepatocyte (liver)

4) bilirubin is converted into urobilinogen, further broken down in small intestine and eventually excreted as waste via large intestine

• once haptoglobin has depleted, hemoglobin is excreted in urine.

What is a way to find out a way to identify if an individual has increased amounts of Intravascular hemolysis?

• 1st symptom is blood in the urine

What does haptoglobin form in the Intravascular hemolysis? And where does it circulate?

• forms the haptoglobin-hemoglobin complex and haptoglobin takes hemoglobin to the liver

• Circulates in the plasma in the peripheral blood

What does haptoglobin bind to in order to prevent what ?

• binds to hemoglobin complex to prevent renal excretion (exrection out of kidneys)

What happens in the liver in Intravascular hemolysis?

• Iron is transported by transferrin into the bone marrow to produce RBC

• Amino acids is sent to the amino acid pool to produce proteins ‘

• Protoporphyrin ring is converted into bilirubin

What does haptoglobin bind to and what does hemoglobin bind to?

• Haptoglobin binds to hemoglobin

• Hemopexin binds to methemoglobin (protein changes: hemopexin-methemoglobin complex + smaller amounts in RBC)

What are the protein carriers?

• Transferrin: transport protein for iron

• Haptoglobin: transports hemoglobin diners

• Hemopexin: transports methemoglobin

• Albumin: transport protein for bilirubin to the liver