1. Lecture 22 Homeostasis

2. Two Ways to Regulate Negative Feedback -O 2 and CO 2 levels in blood -Heart rate -Blood pressure -Metabolite levels -Water and ions -pH -Body temperature Positive Feedback -Depolarisation during action potential -Oxytocin

3. 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.

4. 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.

5. 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.

6. 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%

7. 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.

8. Control of Blood Glucose Respiratory substrate needed continuously by cells. Normal level 90mg/100 cm 3 blood, can be as low as 70mg during fasting or as high as 150mg following a meal. Six hormones and two negative feedback pathways.

9. Regulation of Blood Glucose Levels insulin 90mg/100 cm 3 pancreas Adrenal glands hypothalamus Liver- glycogen, cell respiration, fat Muscle- glycogen, cell respiration Other cells- cell respiration Beta cells islets of Langerhans Alpha cells Islets of Langerhans - glucagon Adrenal medulla adrenaline Pituitary Gland – adrenocorticotropic hormone stimulates adrenal cortex to produce cortisol Thyroid stimulating hormones stimulates thyroid gland to produce thyroxine rise fall Liver Glycogen - glucose Protein - glucose Normal glucose level

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.