Physiology 16 Flashcards
When is lactate produced during glycolysis?
During the cytosolic phase, excess pyruvate is converted to lactate by lactate dehydrogenase
In what situations does significant conversion of pyruvate to lactate occur?
When pyruvate production exceeds mitochondrial capacity to use it:
- In cells without mitochondria (eg. erythrocytes)
- Increasing anaerobic metabolism
- Rapid increase in metabolic rate
- When glucose metabolism exceeds oxidative capacity of mitochondria
Outline the metabolic pathways for lactate
First lactate is converted back to pyruvate by LDH, then it can:
- Move into mitochondria for use in citric acid cycle
- Be converted to glucose in the liver/kidneys (gluconeogenesis)
- Undergo transamination to alanine in the liver/kidneys
Where is LDH found?
In all cells except pancreatic islet cells
Which tissues are the most active in producing lactate?
Muscles
Erythrocytes
Outline the normal use of lactate in the body
75% is oxidised for use as substrate in the citric acid cycle
25% is transported to the liver where is undergoes gluconeogenesis in the Cori cycle
Outline the Cori Cycle
- Describes the cycle of use of glucose between the muscles and liver, including glycogenolysis and gluconeogenesis
- Gluconeogenesis can only occur in aerobic conditions
- Muscle and sympathetic activity cause glycogenolysis in the muscles, and the glucose produced is glycolysed, producing lactic acid.
- Lactic acid travels to the liver, is converted to pyruvate and then glucose through gluconeogenesis.
- This glucose can then be stored via glycogenesis or transported back to the muscles where it may be used for glycolysis or gylcogenesis depending on level of activity.
How much albumin is produced by the liver per day?
12g
What types of molecules are bound by albumin?
Fatty acids, unconjugated bilirubin, Fe, Cu, bile acids, drugs, toxins
What serum proteins other than albumin are produced by the liver?
What do they transport?
Transferrin - Fe Haemopexin - Haem Transcobalamins - B12 Folate binding protein - Folate Caeruloplasmin - Cu Haptoglobin - Hb Lipoproteins - Triglycerides, cholesterol, bile acids Thyroxine binding globulin - Thyroxine
Which coagulation factors are produced in the liver?
II, VII, IX, X
Why is vitamin K needed for the production of coagulation factors in the liver?
Required for post-translational formation of γ-carboxyglutamyl residues which are essential for physiological activation
What hepatobiliary problems may affect clotting? How is it affected?
PT may be prolonged in conditions that:
- Cause hepatocellular damage (and thus synthetic function)
- Cause cholestasis (and thus reduce absorption of vit K)
What is the liver’s role in production of inhibitors of haemostasis?
Major site of production for:
- Antithrombin III
- Protein C
- Protein S
What are the sources of ammonia in the body?
- Catabolism of protein and nucleic acids
- Production by intestinal flora (from dietary protein and urea)
How is ammonia processed following production?
Absorbed via intestine into portal venous blood
Metabolised in the liver such that almost all ammonia is removed from the blood.
What is a normal systemic blood ammonia level?
In what form is it most abundant?
<35 umol/L
At pH 7.4 it is mostly in its ionised form - the quaternary ammonium ion NH4+
How is ammonia metabolised in the liver?
How is this related to pH regulation?
Conversion to urea and glutamine
H+ released from NH4+ in the process neutralises excess HCO3- produced from amino acid catabolism, thus regulating pH
How is urea excreted?
- Urea is electroneutral
- Transported by facilitated diffusion
- Excreted renally
Where does the urea cycle take place?
What happens in each place?
In the mitochondria and cytosol of hepatocytes, Z1 > Z2 > Z3
The first steps take place in the mitochondria where NH4+ + ornithine -> Citrulline
The next steps take place in the cytosol where Citrulline + aspartate -> Urea + ornithine + fumarate
How much urea is recycled?
30% of urea produced is hydrolysed in the colon, producing ammonia which is reabsorbed and converted back to urea in the liver
How is ammonia metabolised other that via urea production?
Where does this take place?
Coversion to glutamine by glutamine synthetase in perivenular (Z3) hepatocytes (scavenger cells).
This is a high affinity system, thus damage to these cells produces hyperammonaemia
