© Pearson Education Ltd 2009 This document may have been altered from the original Week 5 Define the term excretion. Explain the importance of removing metabolic wastes from the body, including carbon dioxide and nitrogenous waste. Describe the formation of urea in the liver, including an outline of the ornithine cycle. Describe the roles of the liver in detoxification. Describe, with the aid of diagrams and photographs, the histology and gross structure of the liver.

Week 5 A diagram showing the positions of the main excretory organs

egestion  Excretion versus egestion  Metabolic waste – substances produced from chemical reaction that may be toxic at high levels in the body Carbon dioxide Nitrogenous waste (urea)

 Urea  Made from deamination of xs amino acids in liver:  Removal of amino group  ammonia + keto acid.  React with CO2 to make less soluble, less toxic  urea. Energy dependent reaction.  Transported in blood plasma  Filtered in kidney to make urine  Carbon dioxide  Respiratory product from all cell  Transported in blood  1) dissolved in blood plasma  2) directly with Hb  3) Forming hydrocarbonate ions (carbonic anhydrase)  Removed by lungs  Respiratory Acidosis  pH less than 7.35  Characteristic symptoms

 Animals that live in water, such as fish, often excrete their nitrogenous waste in the form of ammonia rather than as urea. a. explain why it is possible for them to do this, whereas terrestrial animals cannot. b. Suggest the advantages to aquatic animals of excreting ammonia rather than urea.

 a. The ammonia will quickly dissolve in the large volumes of water around them, and be so diluted that it will not harm the fish.  b. turning ammonia into urea requires energy in the form of ATP, so by excreting ammonia rather than urea, significant amounts of energy are saved.

© Pearson Education Ltd 2009 This document may have been altered from the original Week 5 The liver and its connections to the blood system

 Lies to the right side of body just under diaphragm  Largest internal organ- holds 13% total blood at any one time- can store & release blood acting as a reservoir to compensate for smaller changes in blood volume  Uses up to 20% total energy in body  Made of left & right lobes enclosed by fibrous capsule (Glissons Capsule)  Each lobe formed from hexagonal lobules (100,000)  Dual blood supply: receives blood from 2 blood vessels

LUNG HEART LIVER INTESTINE BODY Pulmonary Artery Aorta Pulmonary Vein Vena Cava Hepatic artery Hepatic Vein Hepatic Portal vein

LUNG HEART LIVER INTESTINE BODY Pulmonary Artery Aorta Pulmonary Vein Vena Cava Hepatic artery Hepatic Vein Hepatic Portal vein

 How will the composition of blood travelling in the HEPATIC PORTAL VEIN differ from that in the HEPATIC ARTERY?

 Hepatic portal vein  more carbon dioxide.  more monosaccharides, amino acids, vitamins, minerals and lipids (transported as lipoproteins) than the blood in the hepatic artery. Eaten recently?

What does the liver do? ENDOCRINE EXOCRINE

What does the liver do? Synthesis Controls levels of…. Plasma proteins (inc clotting factors) Red blood cells Bile Cholesterol Heat Lipid levels (storage in adipose) Glucose Removal of…. Bilirubin (haem group from old RBC Used hormones Detoxification of… Alcohol drugs Stores…. Glucose (glycogen) Iron Key Vitamins

 Main categories:  Secretion Glucose, bile, lipids, Bile  Protein & Lipid synthesis: cholesterol synthesis,lipoproteins, plasma proteins (prothrombin, fibrinogen- clotting factors)  Metabolic Functions: Lipids, carbs (gluconeogenesis) and protein control (dealing with xs amino acids: deamination)  Storage metabollites: glycogen, vitamins A, D, and B12, iron (recycling Haem group from rbc ’ s).  Detoxification

 Main categories:  Bile secretion into ducts to gallbladder digestive, cholesterol transport and absorption.  Storage glucose (glycogen) vitamins A,D,E,K, B12.minerals (copper, iron), saturated fats (chloresterol)  Clearance/Transformation/Purification (metabolism): Ammonia (deamination), transamination of non essential amino acids (ornithine cycle), drugs, Billirubin (RBC breakdown product) Hormones- to prevent continued influence )ie oestrogen, testosterone  Fighting infections: Kupffer cells, activates macrophage system

 Produce bile that is stored in the gall bladder between meals and released into small intestines: ▪ Typically up to 800 ml daily ▪ Bile salts - emulsify fats ▪ Important for absorption of fat soluble vitamins from digested food (Vit. D,E,K & A) ▪ Neutralisation of excess acidity from stomach ▪ Bactericidal role (defence)

 Make up roughly 80% of the mass of the liver  Nuclei are distinctly round, most single nucleus, some binucleate cells.  Hepatocytes are exceptionally active in synthesis of protein and lipids for export therefore have large quantities of both rough and smooth endoplasmic reticulum and Golgi membranes.  Glycogen granules and vesicles containing very low density lipoproteins are readily observed.

DELIVERS BLOOD IN TO LIVER LOBULE SPECIALISED LIVER CELL- MICROVILLI SPACE BETWEEN LIVER CELL AND SINUSOID (BLOOD PLASMA) CHANNEL SPECIALISED MACROPHAGE CELL OUTSIDE OF LOBULE INSIDE OF LOBULE BLOOD VESSEL

© Pearson Education Ltd 2009 This document may have been altered from the original The arrangement of liver cells into cylindrical lobules Interlobular vessels (triad) Blood moves from outside of lobule from HPV and HA  HV Blood from HPV and HA mix and enter channels called SINUSOIDS The branches of HV have thin vessel walls and receive more blood from the sinusoids from each plate (layer) of lobule: link to from bigger branches Hepatocytes lining the SINUSOIDS absorb products in blood and secrete products into the blood as it flows over them.

© Pearson Education Ltd 2009 This document may have been altered from the original The arrangement of liver cells in a lobule

 Direction of blood outside  inside lobule  Dilated capillaries: endothelial cell wall  SPACE of Disse or PERISINUSOIDAL SPACE  Hepatocytes have microvilli (increase surface area of liver cells: x6)  Kupffer cells in SINUSOID: phagocytic cells (derived froim monocytes). Ingest bacteria from blood. Breakdown billirubin for absorption into hepatocytes  Hepatocytes  Release: plasma proteins (prothrombin, fibrinogen, albumin), lipoproteins (endocrine function of liver), cholesterol  Absorb: insulin, glucose, minerals, vitamins, blood borne toxins for detox.

 Hepatocytes separated by second channel: bile canaliculi (plural)  Hepatocytes close to bile canaliculi rich in Golgi vessels reflecting transport of bile constituents into the channels  Transfers fluid inside  outside of lobule  Contents drained into hepatic bile duct: continuous with the common bile duct, which delivers bile into the duodenum, diverting through the gall bladder  Drains up to 1 litre per day

 Bile is a yellowish-green liquid that hepatic cells secrete; VOMIT  It includes water, bile salts, bile pigments, cholesterol, and electrolytes.  Bile salts made from cholesterol.  Bile pigments are breakdown products from red blood cells* (non iron component is billirubin found in blood from spleen removed by Kupffer cells).  Only the bile salts have a digestive function.

 Pear-shaped sac lying on the interior surface of the liver.  Connected to liver via bile ducts merge to form the common bile duct leading to the duodenum.  A sphincter muscle controls the release of bile from the common bile duct.  Blockage of any duct billirubin into blood not bile: jaundice  Gallstones: cholesterol lumps can be calcified and large (surgery, UV) water balance problem

Pancreas Gallbladder Liver

 Emulsify fats – act like a detergent.  Easer digestion by lipases and absorption into the lymphatic capillaries in the villi.  Aid in the absorption of fatty acids, cholesterol, and certain vitamins.

1.What is the functional unit of the liver called? 2.What are the main functions of the liver? 3.What is the triad? 4.What is the sinusoid? 5.What fills the bile canaliculi? 6.What is the name of the phagocytic cell in the liver and where would we find it? 7.Name two products release from the hepatocytes into the blood 8.Name two products removed and metabolised from the blood by the liver.

PRODUCTION OF IMPORTANT PLASMA PROTEINS Soluble globular proteins in the blood. All except immunoglobulins (antibodies) made in the liver. ALBUMIN (& globulins), PROTHROMBIN, FIBRINOGEN

PRODUCTION OF IMPORTANT PLASMA PROTEINS Soluble globular proteins in the blood. All except immunoglobulins (antibodies) made in the liver. ALBUMIN (& globulins), PROTHROMBIN, FIBRINOGEN TRANSAMINATION Converting one type of amino acid to another (exc. 8 essential aa’s) DEAMINATION AND FORMATION OF UREA XS proteins/amino can not be stored. Removal of nitrogen group  ammonia (toxic)  urea (Ornithine cycle)

Converted to pyruvate and then glucose (gluconeogenesis)

© Pearson Education Ltd 2009 This document may have been altered from the original Week 5 The ornithine cycle

GLUCONEOGENESIS Vital role in synthesis and control of cholesterol GLYCOGENOLYSIS GLYCOGENESIS ALPHA CELLS  GLUCAGON BETA CELLS  INSULIN PROMOTED BY ADRENALINE Synthesis of “new” glucose (ornithine cycle- pyruvate  glucose) from amino acids, glycerol, other non hexose sugars Promoted in fasting (starvation) and by adrenaline (fight flight response) Increased glucose uptake by hepatocytes: glucose increases in cells  glycogen (insoluble, compact, no effect on water potential)

 What type of reaction will be involved in converting glucose to glycogen?

 A condensation reaction; glycosidic bonds will be formed between glucose molecules.

GLUCONEOGENESIS Vital role in synthesis and control of blood sugar (glucose) GLYCOGENOLYSIS GLYCOGENESIS ALPHA CELLS  GLUCAGON BETA CELLS  INSULIN PROMOTED BY ADRENALINE Synthesis of “new” glucose (ornithine cycle- pyruvate  glucose) from amino acids, glycerol, other non hexose sugars Promoted in fasting (starvation) and by adrenaline (fight flight response)