Download Lecture #22 - Suraj @ LUMS

Lecture 22
Homeostasis
Two Ways to Regulate
• Negative Feedback
-
O2 and CO2 levels in blood
Heart rate
Blood pressure
Metabolite levels
Water and ions
pH
Body temperature
• Positive Feedback
- Depolarisation during action potential
- Oxytocin
Components of Regulatory System
• To regulate the internal environment, the following
basic process are common to all regulatory systems:
• Some imbalance (deficit or excess occurs).
• Some detector or detectors which sense deviations from
stable levels.
• Some central processing system -- hypothalamus.
• Effectors capable of remedying the imbalance -involuntary or reflexive.
• Complex learned behaviours - aid in maintaining a
balance.
• Planning external aids to deal with future imbalances.
The Liver
• Largest gland in the body (weighs about 1500 g).
• Two lobes: left and right (lower than left). .
• 1/3 of blood flows into the liver from the aorta and
2/3’s enter from the portal vein ( absorbed food
material from gut).
• Blood exits via left and right hepatic veins into
inferior vena cava.
• The cells of the liver are known as hepatocytes.
Functions of the Liver
• Carbohydrate, fat and protein metabolism.
• Vitamin/mineral storage.
• The liver of the fetus makes red blood cells, eventually
taken over by cells in the bone marrow.
• Breakdown of heamoglobin.
• Bile production – bile acids, bile pigments (bilirubin),
cholesterol, bile salts (cholesterol) for lipid breakdown.
Blood Glucose Is Controlled Mainly
by the Liver
• Immediately after meals blood glucose comes from meal
• Between meals blood glucose comes from the liver &
kidneys
• Only the liver and kidneys can release glucose into the
blood (requires a special enzyme that converts glucose
metabolites to glucose, which can be transported across the
cell membrane)
• Liver provides 80% of blood glucose supply between
meals, the kidney 20%
Glucose Synthesis in Liver
• Liver makes glucose in 2 ways:
- Breaks down liver glycogen (glycogenolysis).
- Converts other types of small molecules into glucose
(gluconeogenesis).
• Many small molecules can be converted to glucose:
- Lactate & pyruvate: mainly come from muscles.
- Glycerol: supplied by adipose tissue when triglycerides are
broken down.
- Fatty acids cannot be converted into glucose, but: Fatty acid
metabolism indirectly supports gluconeogenesis by
producing AcetylCoA. AcetylCoA activates and inhibits key
enzymes, promoting glucose formation.
- Amino acids can be converted to glucose.
Control of Blood Glucose
• Respiratory substrate needed continuously
by cells.
• Normal level 90mg/100 cm3 blood, can be
as low as 70mg during fasting or as high as
150mg following a meal.
• Six hormones and two negative feedback
pathways.
Regulation of Blood Glucose Levels
Liver-glycogen, cell respiration,
insulin
rise
pancreas
fat
Muscle-glycogen, cell respiration
Other cells-cell respiration
Beta cells islets of Langerhans
Normal glucose level
90mg/100 cm3
fall
Alpha cells Islets of
pancreas Langerhans - glucagon
Adrenal medulla adrenaline
Adrenal glands Pituitary Gland –
adrenocorticotropic hormone
hypothalamus stimulates adrenal cortex to
produce cortisol
Thyroid stimulating
hormones stimulates thyroid
gland to produce thyroxine
Liver
Glycogen - glucose
Protein - glucose
Alcohol
• Alcohol, or ethyl alcohol (ethanol).
• Alcohol is metabolized extremely quickly by the body.
Unlike foods, which require time for digestion, alcohol
needs no digestion and is quickly absorbed.
• Once alcohol reaches the stomach, it begins to break down
with the alcohol dehydrogenase enzyme.
• This process reduces the amount of alcohol entering the
blood by approximately 20%. (Women produce less of
this enzyme, which may help to partially explain why
women become more intoxicated on less alcohol than
men.).
• In addition, about 10% of the alcohol is expelled in the
breath and urine.
Liver and Alcohol
• Though alcohol affects every organ of the body, it’s most
dramatic impact is upon the liver.
• The liver cells prefer fatty acids as fuel, and package
excess fatty acids as triglycerides.
• When alcohol is present, the liver cells are forced to first
metabolize the alcohol, letting the fatty acids accumulate,
sometimes in huge amounts.
• Alcohol metabolism permanently changes liver cell
structure, which impairs the liver’s ability to metabolize
fats.
• This explains why heavy drinkers tend to develop fatty
livers.
• The liver is able to metabolize about ½ ounce of ethanol
per hour.
How the Liver Breaks Down Alcohol
• The alcohol dehydrogenase enzyme breaks down alcohol
by removing hydrogen in two steps:
1. Alcohol dehydrogenase oxidizes alcohol to
acetaldehyde.
2. Acetaldehyde dehydrogenase oxidizes the
acetaldehyde to acetyl CoA. These reactions produce
hydrogen ions (acid). The B vitamin (coenzyme NAD)
picks up these hydrogen ions (becoming NADH).
• During alcohol metabolism, NAD becomes unavailable for
the many other vital body processes for which it is needed,
including glycolysis, the TCA cycle and the electron
transport chain.
Alcoholism & Liver Disease
• Fatty liver is the first stage of liver deterioration in
heavy drinkers.
• It interferes with the distribution of oxygen and
nutrients to the liver’s cells.
• If the condition persists long enough, the liver
cells will die, forming fibrous scar tissue (the
second stage of liver deterioration, or fibrosis).
• Some liver cells can regenerate with good
nutrition and abstinence.
• In the last stage of deterioration, or cirrhosis, the
damage to the liver cells is the least reversible.
Alcoholic Hepatitis and Cirrhosis
• Most common liver disease.
• Characterized by hepatomegaly, increase in transaminase
levels, and serum bilirubin concentration.
• Inflammation due to accumulation of fat and the effect of
acetaldehyde on liver cells.
• Symptoms may include: abdominal pain, anorexia,
vomiting, weakness, diarrhea, weight loss, fever.
• Distorted liver structure inhibiting blood flood (portal
hypertension) varices and accumulation of fluid in
abdominal cavity (ascites), varices may cause acute
bleeding in gastrointestinal tract.
• Impairment of liver function causing high ammonia levels.
• Malnutrition in the Alcoholic - alcohol replaces food thus
displacing energy and nutrients.
Breakdown of Haemoglobin
• Phagocytic cells in liver, spleen and bone marrow
breakdown red blood cells.
• Heamoglobin released and dissolves in plasma.
• Taken up by macrophages where broken down
into haem and globin (amino acids).
• Iron removed, green pigment biliverdin left.
• This is converted into bilirubin, yellow pigmented
molecule.