IHO: Week 1 Flashcards
What are the plasma proteins found in blood plasma?
- Albumin (58%)
- Globulins (38%)
- Fibrinogen (4%)
What is the function of plasma proteins?
- Transport nutrients, metabolites, and hormones throughout the body
- Defend against infection
- Maintain integrity of circulation through clotting
- Maintain proper water distribution throughout body (oncotic pressure)
What is oncotic pressure and how is it calculated?
Oncotic pressure (pi)= form of osmotic pressure exerted by plasma proteins in blood vessels
Jv = Kf ([Pc-Pi] - o[pi c -pi i])
What are the effects of oncotic pressure at arteriolar and venous ends of blood vessels?
Arteriolar end hydrostatic pressure exceeds sum of tissue pressure (oncotic) which is largely related to albumin –> fluid leaves blood vessel
Venous end hydrostatic pressure is < tissue oncotic pressure causing fluid to enter the blood vessel
The _____ synthesizes and releases more than 90 percent of the _______ ________, including all albumins and fibrinogen, most globulins, and various prohormones.
liver
plasma proteins
What is the main function of albumin?
- Carrier of free fatty acids, calcium, zinc, steroid hormones, copper, and bilirubin
- Binds drugs which can decrease their effective concentration and lengthen lifetime in circulation
- Used to assess liver function
What is main function of globulins?
Globulins include antibodies and transport globulins.
- Antibodies attack foreing proteins and pathogens
- Transport globulins bind small ions, hormones, or compounds that might be lost at the kidneys/have low solubility
ex. transferrin (metalloprotein), apolipoprotein (ApoE/B, etc.)
What is main function of fibrinogen?
- Clotting; multiple fibrinogen molecules interact forming large insoluble strands of fibrin (basic framework for blood clots)
What are the two different ways anemia can be classified?
- RBC size (mean corpuscular volume -MCV): micro-, normo-, and macrocytic
- Hemoglobin concentration (mean corpuscular hemoglobin concentration - MCHC)
What is the normal range for MVC and what conditions represent microcytic and macrocytic MVC?
- Normal: 80-100 fls
> 100 fls (macro) - B12 def
<80 fls (micro) - Iron def
What is normal range for MCHC?
32-37 g/l (normochromic)
What is the journey of heme to conjugated bilirubin?
Senescent RBCs are phagocytosed by reticuloendothelial cells (macrophages typically) and heme is removed. The heme is then stripped of Fe and converted into biliverdin (green in color). The biliverdin is the converted to bilirubin (orange-yellow in color) and released into the bloodstream bound to albumin where it is transported to the liver for excretion in bile. It is in the liver that bilirubin is conjugated to UDP-glucuronate to be eliminated via urine or feces.
What conditions result when heme degradation goes array?
- Hemoglobinuria = large numbers of RBCs break down in bloodstream, urine may turn red or brown
- Hematuria = presence of intact RBCs in urine which occurs after kidney damage or damage to vessels along urinary tract
- Jaundice = bilirubin is not conjugated in the liver to UDP-glucuronate and diffuses into peripheral tissues if the bile ducts are obstructed
Methemoglobinuria can be congenital or acquired, what are the different etiologies for each condition?
- Congenital: deficiency in cytochrome b5 reductase; inherited hemoglobin M disease
o Single AA substitution in heme-binding pocket stabilizes ferric state (Fe3+) - Acquired: ingestion of oxidants such as nitrites, quinones, aniline, sulfonamides; benzocaine, lidocaine, or dapsone use
o Tx: reducing agents - ascorbic acid or methylene blue
What impact of 2,3-BPG, temperature, pH, and Co2 have on affinity of hemoglobin for oxygen?
Shift curve to right (O2 goes to tissue; decreased Hg-O2 affinity): increased H+, CO2, temp, [2,3-BPG]
Shift curve to left (O2 remains bound to Hbg): decrease H+, temp, CO2, [2,3-BPG]
What RBC membrane proteins give rise to the deformable nature of a RBC?
- Spectrin: heterodimer of alpha and beta subunits
- Actin: connects multiple spectrins to create a branched cytoskeleton
- Ankyrin: interacts with band 3 and spectrin
- Band 4.2: stabilizes ankyrin-spectrin connection
- Band 4.1: anchors spectrin skeleton to glycophorin C and actin complex
How is Heme Iron absorbed?
- Heme is released from ingested proteins by low pH proteolytic activity in the stomach
- Heme is thought to be absorbed across the duodenal brush border, but mechanisms are poorly understood;
• DMT1 mediates proton-dependent Fe2+ import
• HCP1 transports dietary heme iron - Heme oxygenase releases iron from heme; iron from heme and non-heme iron are now in pool of free iron
• Excess iron stored in ferritin
How is Non-heme Iron absorbed?
- Non-heme iron is usually present in the ferric form (Fe3+)
- The acidic pH of the stomach favors conversion of Fe3+ to Fe2+, which is more soluble
- Duodenal cytochrome b reductase (DCYTB) at duodenal brush border converts Fe3+ to Fe2+
- Divalent metal transporter 1 (DMT1) moves ferrous (Fe2+) iron into the enterocyte
How is iron exported from the enterocyte?
- Ferroportin is the only putative iron exporter identified to date.
- Ferroportin takes ferrous iron from the enterocyte and transports it to the portal plasma
- Hephestin (cerulopasmin in non-enterocytes) at the BL membrane of enterocytes converts Fe2+ to Fe3+
- Fe3+ then transported via transferrin in the portal bloodstream
Iron can also be removed through the sloughing of enterocytes from the body
What are some promoters and inhibitors of iron absorption?
- Promoters: Ascorbic acid, Citric Acid, Some spices, B-carotene, Alcohol
- Inhibitors: Phytic acid, Polyphenols, Tannins, Calcium
How is iron homeostasis maintained?
Hepcidin is a key regulator of iron homeostasis.
- Hepcidin is produced in response to inflammation (AOCD, IL6) and results in increased iron stores
- Hepcidin binds to ferroportin and triggers internalization/degradation of lysosomes which decreases Fe release from macrophages, enterocytes, and hepatocytes
- Net result: increased intracellular [Fe], decreased bioavailability of Fe
What happens in hepcidin deficiency and excess hepcidin?
Since hepcidin regulates iron stores in the body a hepcidin deficiency would result in iron overload and an excess of hepcidin is implicated in AOCD
Ultimately, hepcidin prevents the release of iron from cells.
What increases and decreases transcription of Hepcidin through the HAMP gene?
INcreases: inflammation, plasmatic iron increasing, genetic abnormalities (IRIDA syndrome)
Decreases: hypoxemia, anemia, iron def, erythropoietin, genetic abnormalities (hereditary hemochromatosis)
How is ferritin and transferrin synthesis mediated?
Both depend on iron levels:
Low iron: ferritin has IRP bound to 5’UTR halting transcription of its mRNA; transferrin has IRPs bound at 3’UTR which stabilizes the mRNA allowing transcription to occur
High iron: IRPs leave ferritin mRNA allowing transcription to occur; IRPS leave transferrin mRNA which causes it to be degraded
What are the iron findings for AOCD and Iron Deficiency?
Serum Iron Serum Ferritin Transferrin Iron Sat % Total Iron Binding Capacity (TIBC) Transferrin
AOCD:
- Serum Iron: decreased
- Serum Ferritin: increased
- Transferrin Iron Sat %: decreased
- Total Iron Binding Capacity (TIBC): decreased
- Transferrin: decreased
Iron Deficiency:
- Serum Iron: decreased
- Serum Ferritin: decreased
- Transferrin Iron Sat %: decreased
- Total Iron Binding Capacity (TIBC): increased
- Transferrin: increased
What are the symptoms and pathophysiology of Acute Intermittent Porphyria?
Symptoms:
- GI (95%): pain, vomiting, constipation, tender abdomen (not rigid)
- Hyponatremia in severe attack
- Neuropathy (2/3): motor, sensory, psychiatric
- CV (70%): increased BP, tachycardia
- Photosensitivity NOT present
Pathophys: gene mutation in PBG deaminase (autosomal dominant; chrom. 11) resulting in accumulation of PBG and ALA
