Week 5 Flashcards
Describe the neuronal control of the GIT
Parasympathetic from vagus:
- cholinergic and excitatory
Sympathetic fibres are post-ganglionic to:
- BVs
- smooth muscle
- glands
- inhibit acetyl choline release from plexuses
Describe the GIT hormonal control
What are gastric secretion made of
acid
bicarbonate (base to neutralise acid)
mucus (protects lining os stomach)
How can gastric secretions be modified & give examples
neutralisation
- e.g. magnesium hydroxide & trisilicate
mucosal protection
- e.g. sucralfate (coats lining of stomach)
absorbents
- e.g. activated charcoal (binds bacteria & toxins)
histamine antagonist
- e.g. cimetidine
proton pump inhibitors
- e.g. omeprazole
Misoprostol (protects lining & prevents ulcers)
Why might we want to neutralise gastric secretions
ruminal acidosis
gastritis
oesophagitis
What is the effect of histamine antagonists on gastric secretion
Inhibits gastrin, histamine and acetylcholine stimulated secretion
Pepsin secretion falls (less volume of fluid)
Get a rebound increase on withdrawal
What is the effect of proton pump inhibitors on gastric secretion
highly effective
irreversible binding to ATPase
basal & stimulated release is inhibited
What is the effect of Misoprostol on gastric secretion
stable analogue of PGE1
inhibits acid secretion
increases mucosal blood flow
increases uterine contraction
What are the 2 centres that control emetics
chemo receptor trigger zone
- chemical stimuli
- BBB permeable
- also involved in motion sickness
- impulses pass to vomiting centre
vomiting centre in brainstem:
- coordinates & integrates vomiting
Describe the pathophysiology of vomiting
Impulse to vomiting centre via central, peripheral pathways or vestibular apparatus
substance P (neurotransmitter) binds to NK-1 receptors at cell membrane
signal travels via vagus nerve to abdominal muscles + diaphragm => vomiting
How can vomiting be induced (emetic examples)
apomorphine (dopamine agonist)
- IV or mucosa
- rapid effect
alpha2 agonists
- e.g. xylazine
syrup of Ipecac
- direct irritant
- cardiotoxicity in high doses
What are some anti-emetics
Dopamine antagonists
Cerenia (maropitant)
Anti-histamines
Anticholinergics
Cannabinoids
Describe the action of metaclopramide and domperidone (dopamine antogonists) as anti-emetics
Short action so need to infuse IV
Metaclopramide - centrally acting (CRTZ)
Domperidone - peripherally acting
Increase gastric emptying and increased motility
Do not use if vomiting due to obstruction (sends obstruction further down GIT)
What are some dopamine antagonists (anti-emetics)
phenothiazine derivatives
metaclopramide and domperidone
Describe the action of Cerenia as an anti-emetic
NK1 antagonist
competes with substance P
How is diarrhoea managed
maintenance of fluid balance:
- IV fluid therapy (Hartmann’s solution)
- oral fluids
- anti-infectives e.g., zinc = immune stimulant
why may you want to modify intestinal motility in cases of diarrhoea
reduce pain
increase transit time and reabsorption window
What are the 2 main classes of antimotility (spasmolytics) drugs
opiates
- increase contractions but decrease propulsion –> increased large intestinal tone –> constipation
- e.g. morphine, loperamide
muscarinic antagonists
- inhibit acetylcholine stimulatory effects from vagus nerve
- e.g. hyoscine (buscopan)
What drugs improve gut motility
laxatives
- saline & hyperosmotic agents
- irritants to stimulate movement
- bulk producing agents
prokinetics
How does bulk (a laxative) improve gut motility
e.g. agar bran
polysaccharide polymers that are not easily digested
form hydrates bulk in gut
hold water
promote peristalsis
How do osmotic laxatives aid intestinal motility?
Poorly absorbed solutes
Lactulose - broken down to lactic acid => lower pH => traps ammonia and water in gut => softens faeces => eases motility
What drugs are used in idiopathic inflammatory bowel disease?
anti-inflammatory
- steroids such as prednisolone
- sulphasalazine (pro-drug = broken down into active substance in liver)
What are antifoaming agents used for and give an example
Define catabolism and anabolism
What are metabolic pathways
Describe the intrinsic regulation of metabolism
Reactions which self-regulate to respond to changes in the levels of substrate or products
Describe extrinsic control of metabolism
a cell changing its metabolism in response to signals from other cells
Fill in the rest of the negative feedback loop for thermoregulation
Describe the basic reactions that produce energy
Energy comes from breakdown of glucose, fatty acids and amino acids into acetyl CoA
Acetyl CoA enters the Krebs cycle to produce energy in 2 ways:
- as ATP (substrate-level phosphorylation)
- through NADH/FADH2 which is processed through oxidative phosphorylation to produce more ATP
Describe the ATP-ADP cycle
as body functions use up energy, ATP is converted to ADP and an inorganic phosphate
ADP and inorganic phosphate are used to create ATP for energy
Describe the Krebs cycle
Acetyl CoA (precursor to cycle) is produced from AAs, fatty acids and glucose
Series of reactions that oxidise Acetyl CoA to CO2
Electrons lost from these reactions are used in oxidative phosphorylation to produce ATP
Some steps release energy that is directly captured as ATP (substrate level-phosphorylation)
Describe oxidative phosphorylation
Electrons from the Krebs cycle are transferred into the electron transport chain in mitochondrion
via an electron carrier
As electrons pass down the electron transport chain it releases energy which is used to pump protons out of the mitochondrion forming an electrochemical gradient
when protons flow back down their gradient they pass through ATP synthase (enzyme) => ATP synthesis
Electrons eventually join O2 to form water
what is resting metabolic rate (RMR)/ basal metabolic rate (BMR)?
energy required to maintain life
expressed in kcal/day
what effects the resting metabolic rate
body size
age
sex
species
body temperature
hyperthyroidism (increase)
hypothyroidism (decrease)
pregnancy & lactation
growth
genetic factors
Describe glucose during the fasting state
~2-4 hrs after a meal blood glucose levels return to basal levels and continue to decrease until the next meal
Insulin levels decline and glucagon levels rise which triggers release of fuels from the body stored
How is blood glucose maintained
during fasting liver produces glucose by glycogenolysis (release of glucose from glycogen) and gluconeogenesis (synthesis of glucose from noncarbohydrate compounds (mainly amino acids but also lactate & glycerol))
when is an animal in a starved state
when an animal has fasted for 3 or more days
prolonged period of low glucose cause animal to die due to lack of appropriate energy sources to maintain vital cells
What is the impact of increased blood glucose levels
increase in blood glucose (after digestion of carbohydrates) is detected by pancreatic islet cells
beta islet cells respond by releasing insulin into bloodstream
insulin signals tissues to store glucose as glycogen or fats
glucagon does the opposite and mobilises stores of glucose when levels are low
What are the 2 fates of glucose in the liver
absorbed by hepatocytes
or
continues through liver & enters general circulation
What happens to glucose if it enters hepatocytes
glucose can have multiple fates in hepatocytes:
- oxidised & used as energy source for hepatocyte
- under influence of insulin, it can be converted to glycogen & stored in liver
- however liver has limited space to store glycogen - can be converted to TAG (triacylglycerol) ready for export out of liver
- storage of TAG in liver can lead to accumulation of fat in liver which prevents normal liver function & causes disease
Describe the exportation of TAG out of liver
What is the importance of glucose in the brain
Brain and neural tissues can only use glucose as substrate for energy
They oxidise glucose via cellular respiration to generate ATP
Glucose is major precursor of neurotransmitters
Clinical signs of low blood glucose are usually neurological
What is the lactate equation
Lactate builds up in anaerobic respiration
Lactate + NAD+ <=> pyruvate + NADH + H+
What is the cori cycle
cycling of lactate & glucose between peripheral tissues & liver
Describe the cori cycle
Lactate released from cells undergoing anaerobic glycolysis (usually muscle cells when O2 conc is low) taken up by liver and oxidised back to pyruvate
Pyruvate use to synthesise glucose (gluconeogenesis) which is returned to blood
Define gluconeogenesis
Describe anaerobic glycolysis in RBC
Glucose is only fuel for RBCs as they lack mitochondria
Glucose used to generate ATP in cytosol via anaerobic glycolysis
Pyruvate formed is converted to lactate and released into blood
Describe the fate of glucose in muscles
exercising skeletal muscles can use glucose from blood or their own glycogen stores
glucose converted to lactate via glycolysis or oxidised completely to CO2 & H2O
Describe the fate of glucose in adipose tissues
Adipocytes oxidise glucose for energy
Adipose cells also metabolise glucose to Acetyl CoA which can be turned into fat and stored
Fill in the table
Where does the body get energy from in starved state
Body limits amount of AAs used for gluconeogenesis in order to preserve muscle mass
Relies on ketones as source of energy
As there is limited glucose, the brain must rely on using intermediate energy source ketone bodies
=> elevated levels of ketone body in blood = ketosis
What is glucose sparing
during starvation the brain uses ketone bodies as energy, therefore it needs less glucose
Glucose is still required for use by RBCs
Less glucose is used by the body to keep some ‘spare’
Liver needs to produce less glucose per hour during prolonged fasting than short periods
How is protein spare during starvation
decreased rate of gluconeogenesis
Reserves proteins for essential functions such as biosynthetic function and new protein synthesis
Describe the role of adipose tissue in starvation
adipose tissue continues to break down its triacylglycerol stores providing fatty acids & glycerol to blood for energy
in liver fatty acids are converted to ketone bodies which are oxidised for energy
How does ketonemia occur
The rate of ketone body production exceeds rate at which they can be used
Why is ketosis common in dairy cows
peak lactation has a high energy demand and cow is incapable of eating enough to support this
Body starts mobilising fats to provides energy => ketone production
Mobilisation of fats results in weight loss
How does the body adapt to a starved state
The breakdown of protein (for AA for gluconeogenesis) becomes tissue or protein specific to guard against vital proteins/cells becoming depleted
This occurs due to elevated levels of cortisol resulting in body adapting to state of starvation
Why do animals die of starvation
Proteins become so depleted that heart, kidney etc stop functioning
Animal can develop infection and not have adequate reserves to mount immune response
Deprived of vitamin and mineral precursors of coenzymes and other compounds necessary for tissue function
Lack of ATP and decreased electrolyte intake, electrolyte composition of cells or blood becomes incompatible with life
What are the functions of proteins
transporters for hydrophobic compounds in blood
cell adhesion molecules
hormones
ion channels
enzymes
Describe protein metabolism after eating
Ingested proteins digested to amino acids in stomach and SI
AAs transported to liver via hepatic portal vein
AAs used to synthesise new proteins (biosynthesis) or converted to energy sources (gluconeogenesis)
AAs also enter general circulation and go into tissues to be synthesised into new proteins
What happens to amino acids in the liver
Synthesis of serum proteins &
biosynthesis of nitrogen-containing compounds that need AA precursors e.g., non-essential AAs, haeme, hormones, neurotransmitters, DNA
Oxidizes AAs to produce energy via Krebs cycle in the fed state
How is the balance of amino acids in the blood maintained
Proteins undergo turnover, constantly being synthesised and degraded, especially in muscle tissue
AAs released by protein breakdown enter the same pool of free AAs in the blood from the diet
Describe protein metabolism in fed state
AAs released from digestion of dietary proteins travel to liver for synthesis of proteins
Excess AAs converted to glucose or triacylglycerols
Triacylglycerols packaged and secreted in VLDL
Glucose stored as glycogen or released into blood if blood glucose levels are low
AAs that pass through the liver are converted to proteins in the cells of other tissues
Describe protein metabolism during fasting
AAs released from muscle protein
Some enter blood
Some are partially oxidised and the nitrogen is stored as alanine and glutamine which enter the blood (gluconeogenic AAs)
AAs enter the liver, nitrogen is converted to urea (excreted in urine) and carbons converted to glucose and ketone bodies which are oxidised for energy
What is beta-oxidation
catabolic process in which fatty acids are broken down to generate acetyl CoA which can enter the krebs cycle
Where do chylomicrons go?
Chylomicrons are synthesised in epithelial cells, secreted into lymph, pass into blood & become mature chylomicrons
then taken to adipose cells
lipoprotein lipase (LP) digests triacylglycerols (TG) of fatty chylomicrons to fatty acids & glycerol
FA oxidised in muscle or stored in adipose cells
remnants of chylomicrons are taken up by liver and digested
What is lipogenesis
metabolic formation of fatty acids from excess dietary carbs (glucose converted to Acetyl CoA => fat synthesis) or protein in the liver
Fatty acids combined with a glycerol molecule => TAGs
How are TAGs exported from hepatocytes
packaged with cholesterol, phospholipids and proteins => VLDL
VLDLs secreted into blood
Describe what happens to TAG in a fed state
- Lipoprotein lipase cleaves TAGs in both VLDL and chylomicrons
- forms fatty acids and glycerol
- Fatty acids enter adipose cells and are activated forming fatty acetyl CoA
- This reacts with glycerol-3-phosphate (formed from glucose) to form TAGs
- stored as large fat droplets in adipose tissue
describe lipid metabolism in starved state
- During fasting - adipose TAGs are mobilised (lipolysis)
- This releases fatty acids and glycerol into blood
- Fatty acids transported in blood with albumin are oxidised for energy in cells
- Glycerol used to produce energy via gluconeogenesis in liver
Increased amount of fat mobilised during starvation as decreased AAs used
How are ketone bodies produced
beta-oxidation of fatty acids produces Acetyl CoA during prolonged fasting
Acetyl CoA converted to ketone bodies in liver
ketone bodies oxidised to produce energy
Describe fatty acid oxidation
Beta-oxidation:
- fatty acid => acetyl CoA + NADH + FADH
Oxidation of acetyl CoA:
- into Co2 in Krebs cycle
- produces NADH+ & FADH2 through oxidative phosphorylation
ATP generation:
- ATP generated from NADH and FADH via respiratory electron chain
What are the 3 ways in which metabolic homeostasis is achieved
What tissues are dependent on glycolysis for all/most of their energy needs?
brain
RBCs
lens of eye
kidney medulla
exercising skeletal muscle
What are insulin counterregulatory hormones
hormones that appose actions of insulin by mobilising fuels
e.g. cortisol, epinephrine & glucagon
How does the release of insulin counterregulatory hormones occur
hypoglycaemia is one of the stress signals that stimulates release of cortisol, epinephrine and norepinephrine
ACTH is released from pituitary => release of cortisol from adrenal cortex when hypothalamic regulatory centre detects low blood glucose
When hypothalamic regulatory centre detects low blood glucose => release of epinephrine from adrenal medulla and norepinephrine from nerve endings
What is the impact of stress on metabolism
SNS => epinephrine and norepinephrine release:
- promotes release of glucagon from pancreas
- promotes glycolysis and gluconeogenesis in hepatocytes
- binds to muscle cell receptors => glycolysis
- activates hormone sensitive lipase => mobilises fatty acids for use as fuel
What is clinical biochemistry
analysis of different body fluids for purpose of diagnosis or monitoring
can asses:
- substrates/products
- enzymes
- hormones
glucose and ketone bodies
to analyse metabolism
triglycerides and cholesterol
What are the 2 categories of liver enzymes
hepatocellular
- contained in hepatocyte
- leak out if there is liver damage
- e.g. AST & ALT
cholestatic
- found on membrane of cells that line bile ducts
- increased conc. in blood if there is issue with flow of bile through liver
- e.g. ALKP & GGT
What is hepatic encephalopathy
What is the calculation for resting energy requirement
What is the maintenance energy requirement
What is the effect of having a high energy intake on biochemistry
high glucose
high liver enzymes
high cholesterol
high urea
high insulin
high triglycerides
what impact does anorexia have on biochemistry?
ketosis
dehydration
body mobilises fat stores => increased fatty acids
Less WBCs due to lack of proteins
Increase liver enzymes
What is hepatic lipidosis
fat accumulates in hepatocytes due to hypoglycaemia as fat is mobilised from adipose tissue and builds up in liver
How does fatty liver syndrome develop secondary to ketosis
Ketosis is caused by excessive mobilisation of fats for energy
The liver can become overwhelmed with large amounts of lipids leading to accumulation in hepatocytes
How can LDA be related to ketosis
Gas builds up in abomasum due to abnormal contraction => floats in abdomen to LHS
Ketosis => inappetence => decreased rumen size => more room for abomasum to move
What is gross energy and why is it not a useful measure in animal nutrition?
Amount of energy in feed
Not the same as the energy they get out of it
In what ways is energy lost from food
Faecal energy
Urine and gas energy
Heat
Maintenance
What is metabolisable energy
measure of how much energy can be used by the animal from a feed
What is hyperlipidaemia
presence of elevated lipid conc in the blood
What is hyperlipaemia
metabolic disease of ponies, miniature horses and donkeys
Fatty infiltration of organs leading to subsequent organ failure
What causes hyperlipaemia
negative energy balance
Decreased feed/energy intake
Insulin resistance
e.g., starvation, lactation, pregnancy, stress, obesity
Describe metabolic pathways that lead to hyperlipidaemia
Low blood glucose => glucagon => lipases
convert triglycerides into glycerol and fatty acids in adipose tissue => FAs and glycerol enter blood
Excess dietary CHO => converted to glucose => converted to fatty acetyl CoA => converted to triglycerides => packaged as VLDLs => into blood
