Where is Calot's triangle located?
Porta hepatis of the liver [where the hepatic ducts and neurovascular structures enter/exit the liver]
What are the border's of Calot's trinalge?
- medial = common hepatic duct - inferior = cystic duct - superior = inferior surface of the liver
Annotate Calot's borders
Contents of Calot's triangle
- Right hepatic artery – formed by the bifurcation of the proper hepatic artery into right and left branches. - Cystic artery – typically arises from the right hepatic artery and traverses the triangle to supply the gall bladder. - Lymph node of Lund – the first lymph node of the gallbladder. - Lymphatics
What is a laraproscopic cholecystecomy procedure and why is Calot's trinalge relevant to this?
The triangle of Calot is of clinical importance during laparoscopic cholecystectomy (removal of the gall bladder). In this procedure, the triangle is carefully dissected by the surgeon, and its contents and borders identified. This allows the surgeon to take into account any anatomical variation and permits safe ligation and division of the cystic duct and cystic artery. Of particular importance is the right hepatic artery – this must be identified by the surgeon prior to ligation of the cystic artery. If Calot’s triangle cannot be delineated (such as in cases of severe inflammation), the surgeon may elect to perform a subtotal cholecystectomy, or convert to open surgery.
Borders of the inguinal triangle
The inguinal triangle is located within the inferomedial aspect of the abdominal wall. It has the following boundaries: Medial – lateral border of the rectus abdominis muscle. Lateral – inferior epigastric vessels. Inferior – inguinal ligament
Contents of the inguinal triangle
Other than the layers of the abdominal wall, the inguinal triangle does not contain any structures of clinical importance.
What does the inguinal triangle demarcate?
However, the triangle does demarcate an area of potential weakness in the abdominal wall – through which herniation of the abdominal contents can occur
Annotate contents of the inguinal triangle
Define a hernia
A hernia is defined as the protrusion of an organ or fascia through the wall of a cavity that normally contains it. The inguinal triangle represents an area of potential weakness in the abdominal wall, through which herniation can occur.
What is a direct inguinal hernia?
In a direct inguinal hernia, bowel herniates through a weakness in the inguinal triangle, and enters the inguinal canal. Bowel can then exit the canal via the superficial inguinal ring and form a ‘lump’ in the scrotum or labia majora. Direct hernias are acquired (usually in adulthood), due to weakening in the abdominal musculature
What is an indirect inguinal hernia?
This is in contrast to an indirect inguinal hernia – where bowel enters the inguinal canal via the deep inguinal ring. By definition, a direct inguinal hernia occurs medially to the inferior epigastric vessels (through the inguinal triangle), and an indirect hernia occurs laterally to these vessels
Define these types of hernias
What is the peritoneal cavity?
Potential space between teh parietal and visceral peritoneum.
What does the peritoneal cavity contain?
It normally contains only a thin film of peritoneal fluid, which consists of water, electrolytes, leukocytes and antibodies. This fluid acts as a lubricant, enabling free movement of the abdominal viscera, and the antibodies in the fluid fight infection. While the peritoneal cavity is ordinarily filled with only a thin film of fluid, it is referred to as a potential space because excess fluid can accumulate in it, resulting in the clinical condition of ascites (see clinical applications)
Greater sac divided by what?
How is the greater sac subdivided?
Greater Sac The greater sac is the larger portion of the peritoneal cavity. It is further divided into two compartments by the mesentery of the transverse colon (known as the transverse mesocolon): Supracolic compartment – lies above the transverse mesocolon and contains the stomach, liver and spleen. Infracolic compartment – lies below the transverse mesocolon and contains the small intestine, ascending and descending colon. The infracolic compartment is further divided into left and right infracolic spaces by the mesentery of the small intestine
How are the supra and infra-colic compartments connected?
The supracolic and infracolic compartments are connected by the paracolic gutters which lie between the posterolateral abdominal wall and the lateral aspect of the ascending or descending colon.
What are subphrenic abscesses?
The subphrenic recesses are potential spaces in the supracolic compartment of the greater sac. They are located between the diaphragm and the liver. There are left and right subphrenic spaces, separated by the falciform ligament of the liver.
Where do subphrenic abscesses typically occur?
Subphrenic abscesses refer to an accumulation of pus in the left or right subphrenic space. They are more common on the right side due to the increased frequency of appendicitis and ruptured duodenal ulcers (pus from the appendix can track up to the subphrenic space via the right paracolic gutter).
Where does the lesser sac [omental bursa] lie?
The lesser sac lies posterior to the stomach and lesser omentum. It allows the stomach to move freely against the structures posterior and inferior to it
How is the omental bursa connected to the greater sac?
The omental bursa is connected with the greater sac through an opening in the omental bursa – the epiploic foramen (of Winslow)
Where is the epiploic forman located?
The epiploic foramen is situated posterior to the free edge of the lesser omentum (the hepatoduodenal ligament)
Peritoneal cavity in males image
Peritoneal cavity in females
In females, there are two areas of note: Rectouterine pouch (of Douglas) – double folding of the peritoneum between the rectum and the posterior wall of the uterus. Vesicouterine pouch – double folding of peritoneum between the anterior surface of the uterus and the bladder
Is the peritoneal cavity closed in females? Why so/not so?
The peritoneal cavity is not completely closed in females – the uterine tubes open into the peritoneal cavity, providing a potential pathway between the female genital tract and the abdominal cavity. Clinically, this means that infections of the vagina, uterus, or uterine tubes may result in infection and inflammation of the peritoneum (peritonitis)
Are infections common in the peritoneal cavity?
Actual passage of infectious material into the peritoneum, however, is rare due to the presence of a mucous plug in the external os (opening) of the uterus which prevents the passage of pathogens but allows sperm to enter the uterus.
Explain the two times peritoneal fluid is sampled [culdocentesis and paracentesis]
Clinical Relevance: Sampling of Peritoneal Fluid Culdocentesis Culdocentesis involves the extraction of fluid from the rectouterine pouch (of Douglas) through a needle inserted through the posterior fornix of the vagina. It can be used to extract fluid from the peritoneal cavity or to drain a pelvic abscess in the rectouterine pouch. Paracentesis Paracentesis is a procedure used to drain fluid from the peritoneal cavity. A needle is inserted through the anterolateral abdominal wall into the peritoneal cavity. The needle must be inserted superior to the urinary bladder and the clinician must take care to avoid the inferior epigastric artery. It is used to drain ascitic fluid, diagnose the cause of ascites and to check for certain types of cancer which may metastasise via the peritoneum, e.g. liver cancer.
Causes and CF of ascites
Ascites refers to an accumulation of excess fluid within the peritoneal cavity. It is typically caused by portal hypertension (secondary to liver cirrhosis). Other causes include malignancy of the GI tract, malnutrition, heart failure, and mechanical injuries which result in internal bleeding. Clinical features of ascites include abdominal distension, abdominal discomfort, nausea, and dyspnoea due to pressure on the lungs from the enlarged abdominal cavity.
Causes and CF of peritonitis
Peritonitis refers to infection and inflammation of the peritoneum. It can occur as a result of bacterial contamination during a laparotomy (open surgical incision of the peritoneum) or it can occur secondary to an infection elsewhere in the GI tract, for example a ruptured appendix, acute pancreatitis or a gastric ulcer eroding through the wall of the stomach. Exudation of fluid into the peritoneal cavity causes the cavity to expand, and due to the somatic innervation of the parietal peritoneum, results in pain Clinical features include pain and tenderness of the overlying skin and the anterolateral abdominal muscles contract to protect the viscera (known as guarding). Other symptoms include; fever, nausea, vomiting, and constipation. Patients may lie with their knees flexed in an effort to relax the anterolateral abdominal wall muscles.
Explain the parietal peritoneum [incl, where it's derived from, nervous supply etc.]
Parietal Peritoneum The parietal peritoneum lines the internal surface of the abdominopelvic wall. It is derived from somatic mesoderm in the embryo. It receives the same somatic nerve supply as the region of the abdominal wall that it lines; therefore, pain from the parietal peritoneum is well localised. Parietal peritoneum is sensitive to pressure, pain, laceration and temperature
What is the peritoneum made up of?
The peritoneum consists of two layers that are continuous with each other: the parietal peritoneum and the visceral peritoneum. Both types are made up of simple squamous epithelial cells called mesothelium
Nervous supply, dermatomes, derivates of the visceral peritoneum
The visceral peritoneum invaginates to cover the majority of the abdominal viscera. It is derived from splanchnic mesoderm in the embryo. The visceral peritoneum has the same autonomic nerve supply as the viscera it covers. Unlike the parietal peritoneum, pain from the visceral peritoneum is poorly localised and the visceral peritoneum is only sensitive to stretch and chemical irritation. Pain from the visceral peritoneum is referred to areas of skin (dermatomes) which are supplied by the same sensory ganglia and spinal cord segments as the nerve fibres innervating the viscera
Cause and Cx of peritoneal adhesions
Damage to the peritoneum can occur as a result of infection, surgery or injury. The resulting inflammation and repair may cause the formation of fibrous scar tissue. This can result in abnormal attachments between the visceral peritoneum of adjacent organs or between visceral and parietal peritoneum. Such adhesions can result in pain and complications such as volvulus, when the intestine becomes twisted around an adhesion resulting in a bowel obstruction.
Give examples of intraperitoneal organs
Intraperitoneal organs are enveloped by visceral peritoneum, which covers the organ both anteriorly and posteriorly. Examples include the stomach, liver and spleen
Main way of dividing the retroperitoneal organs
Primarily retroperitoneal organs developed and remain outside of the parietal peritoneum. The oesophagus, rectum and kidneys are all primarily retroperitoneal. Secondarily retroperitoneal organs were initially intraperitoneal, suspended by mesentery. Through the course of embryogenesis, they became retroperitoneal as their mesentery fused with the posterior abdominal wall. Thus, in adults, only their anterior surface is covered with peritoneum. Examples of secondarily retroperitoneal organs include the ascending and descending colon
Useful mnemonic for recalling abdominal viscera
A useful mnemonic to help in recalling which abdominal viscera are retroperitoneal is SAD PUCKER: S = Suprarenal (adrenal) Glands A = Aorta/IVC D =Duodenum (except the proximal 2cm, the duodenal cap) P = Pancreas (except the tail) U = Ureters C = Colon (ascending and descending parts) K = Kidneys E = (O)esophagus R = Rectum
What is the mesentery?
A mesentery is double layer of visceral peritoneum. It connects an intraperitoneal organ to (usually) the posterior abdominal wall. It provides a pathway for nerves, blood vessels and lymphatics to travel from the body wall to the viscera. The mesentery of the small intestine is simply called ‘the mesentery’. Mesentery related to other parts of the gastrointestinal system is named according to the viscera it connects to, for example the transverse and sigmoid mesocolons, the mesoappendix.
What is th eomentum?
The omenta are sheets of visceral peritoneum that extend from the stomach and proximal part of the duodenum to other abdominal organs.
Distinguish between the greater and lesser omentum
Greater Omentum The greater omentum consists of four layers of visceral peritoneum. It descends from the greater curvature of the stomach and proximal part of the duodenum, then folds back up and attaches to the anterior surface of the transverse colon. It has a role in immunity and is sometimes referred to as the ‘abdominal policeman’ because it can migrate to infected viscera or to the site of surgical disturbance. Lesser Omentum The lesser omentum is a double layer of visceral peritoneum, and is considerably smaller than the greater and attaches from the lesser curvature of the stomach and the proximal part of the duodenum to the liver. It consists of two parts: the hepatogastric ligament (the flat, broad sheet) and the hepatoduodenal ligament (the free edge, containing the portal triad).
What are the peritoneal ligaments?
Peritoneal Ligaments A peritoneal ligament is a double fold of peritoneum that connects viscera together or connects viscera to the abdominal wall. An example is the hepatogastric ligament, a portion of the lesser omentum, which connects the liver to the stomach.
Three main areas of viseceral localised pain
Pain from the viscera is poorly localised. As described earlier, it is referred to areas of skin (dermatomes) which are supplied by the same sensory ganglia and spinal cord segments as the nerve fibres innervating the viscera. Pain is referred according to the embryological origin of the organ; thus pain from foregut structures are referred to the epigastric region, midgut structures are to the umbilical region and hindgut structures to the pubic region of the abdomen. Foregut – oesophagus, stomach, pancreas, liver, gallbladder and the duodenum (proximal to the entrance of the common bile duct). Midgut – duodenum (distal to the entrance of the common bile duct) to the junction of the proximal two thirds of the transverse colon with the distal third. Hindgut – distal one third of the transverse colon to the upper part of the anal canal.
Where may retroperitoneal organ pain and irritation to the diaphragm present?
Pain in retroperitoneal organs (e.g. kidney, pancreas) may present as back pain. Irritation of the diaphragm (e.g. as a result of inflammation of the liver, gallbladder or duodenum) may result in shoulder tip pain.
How may appendicitis present as referred pain?
Initially, pain from the appendix (midgut structure) and its visceral peritoneum is referred to the umbilical region. As the appendix becomes increasingly inflamed, it irritates the parietal peritoneum, causing the pain to localise to the right lower quadrant.
development of the inguinal canal
During development, the tissue that will become gonads (either testes or ovaries) establish in the posterior abdominal wall, and descend through the abdominal cavity. A fibrous cord of tissue called the gubernaculum attaches the inferior portion of the gonad to the future scrotum or labia, and guides them during their descent. The inguinal canal is the pathway by which the testes (in an individual with an XY karyotype) leave the abdominal cavity and enter the scrotum. In the embryological stage, the canal is flanked by an out-pocketing of the peritoneum (processus vaginalis) and the abdominal musculature. The processus vaginalis normally degenerates, but a failure to do so can cause an indirect inguinal hernia, a hydrocele, or interfere with the descent of the testes. The gubernaculum (once it has shortened in the process of the descent of the testes) becomes a small scrotal ligament, tethering the testes to the scrotum and limiting their movement. Individuals with an XX karyotype also have a gubernaculum, which attaches the ovaries to the uterus and future labia majora. Because the ovaries are attached to the uterus by the gubernaculum, they are prevented from descending as far as the testes, instead moving into the pelvic cavity. The gubernaculum then becomes two structures in the adult: the ovarian ligament and round ligament of uterus.
Where is the mid-inguinal point and the midpoint of the inguinal ligament
Wall boundaries of the inguinal canal
The inguinal canal is bordered by anterior, posterior, superior (roof) and inferior (floor) walls. It has two openings – the superficial and deep rings. Walls Anterior wall – aponeurosis of the external oblique, reinforced by the internal oblique muscle laterally. Posterior wall – transversalis fascia. Roof – transversalis fascia, internal oblique, and transversus abdominis. Floor – inguinal ligament (a ‘rolled up’ portion of the external oblique aponeurosis), thickened medially by the lacunar ligament
During periods of intra-abdominla pressure, how is herniation prevented?
During periods of increased intra-abdominal pressure, the abdominal viscera are pushed into the posterior wall of the inguinal canal. To prevent herniation of viscera into the canal, the muscles of the anterior and posterior wall contract, and ‘clamp down’ on the canal
What are the two rings in the inguinal canal?
Rings The two openings to the inguinal canal are known as rings. The deep (internal) ring is found above the midpoint of the inguinal ligament. which is lateral to the epigastric vessels. The ring is created by the transversalis fascia, which invaginates to form a covering of the contents of the inguinal canal. The superficial (external) ring marks the end of the inguinal canal, and lies just superior to the pubic tubercle. It is a triangle shaped opening, formed by the evagination of the external oblique, which forms another covering of the inguinal canal contents. This opening contains intercrural fibres, which run perpendicular to the aponeurosis of the external oblique and prevent the ring from widening.
COntents of the inguinal canal
The contents of the inguinal canal include: Spermatic cord (biological males only) – contains neurovascular and reproductive structures that supply and drain the testes. See here for more information. Round ligament (biological females only) – originates from the uterine horn and travels through the inguinal canal to attach at the labia majora. Ilioinguinal nerve – contributes towards the sensory innervation of the genitalia Note: only travels through part of the inguinal canal, exiting via the superficial inguinal ring (it does not pass through the deep inguinal ring) This is the nerve most at risk of damage during an inguinal hernia repair. Genital branch of the genitofemoral nerve – supplies the cremaster muscle and anterior scrotal skin in males, and the skin of the mons pubis and labia majora in females. The walls of the inguinal canal are usually collapsed around their contents, preventing other structures from potentially entering the canal and becoming stuck
What happens during an inguinal hernia?
A hernia is defined as the protrusion of an organ or fascia through the wall of a cavity that normally contains it. Hernias involving the inguinal canal can be divided into two main categories: Indirect – where the peritoneal sac enters the inguinal canal through the deep inguinal ring. Direct – where the peritoneal sac enters the inguinal canal though the posterior wall of the inguinal canal. Both types of inguinal hernia can present as lumps in the scrotum or labia majora. Indirect Inguinal Hernia Indirect inguinal hernias are the more common of the two types. They are caused by the failure of the processus vaginalis to regress. The peritoneal sac (and potentially loops of bowel) enters the inguinal canal via the deep inguinal ring. The degree to which the sac herniates depends on the amount of processus vaginalis still present. Large herniations are possible in which the peritoneal sac and its contents may traverse the entire inguinal canal, emerge through the superficial inguinal ring, and reach the scrotum. Direct Inguinal Hernia In contrast to the indirect hernia, direct inguinal hernias are acquired, usually in adulthood, due to weakening in the abdominal musculature. The peritoneal sac bulges into the inguinal canal via the posterior wall medial to the epigastric vessels and can enter the superficial inguinal ring. The sac is not covered with the coverings of the contents of the canal..
Three types of vitamin K
Vitamin K can be categorised into three main types: Phylloquinone (Vitamin K1), Menaquinone (Vitamin K2) and artificially synthesised Vitamin K
Properties of vitamin K
Vitamin K is one of four fat-soluble vitamins and has properties essential for blood coagulation and bone health. In this article we’ll be considering the synthesis, function and clinical significance of Vitamin K.
Synthesis of vitamin K
Vitamin K can be categorised into three main types: Phylloquinone (Vitamin K1), Menaquinone (Vitamin K2) and artificially synthesised Vitamin K. Vitamin K1 is found predominantly in leafy green vegetables, such as spinach, brussels sprouts and broccoli. Vitamin K2 is seen in animal foods including meat, eggs and dairy. Vitamin K is absorbed through the ileum and jejunum of the small bowel. As a fat-soluble vitamin, Vitamin K is carried through the enterocytes by a large fat goblet called a micelle. Here, it enters the bloodstream via the lymphatic system. See the ‘Digestion and Absorption’ article for more deta
Function fo vitamin K
Vitamin K is essential for effective blood coagulation and plays a key role in synthesising certain clotting factors found in the clotting cascade. In the liver, it acts as a co-enzyme for γ-glutamyl carboxylase, an enzyme that converts the inactive forms of factors II (prothrombin), VII, IX and X into their active forms through the carboxylation of glutamic acid residues. Vitamin K also helps synthesise Protein C, S and Z. These all contribute to both the intrinsic and extrinsic pathways of the clotting cascade, resulting in the formation of a blood clot.
Causes of vitamin K deficiency
Vitamin K deficiency Vitamin K deficiency can present with abnormal bruising, or frank bleeding. Causes include: Malabsorption – Any condition that affects small bowel absorption e.g. Crohn’s disease, Ulcerative Colitis, short bowel syndrome, or antibiotic overuse resulting in destruction of the gut microbiome. Inadequate intake – Specifically the foods mentioned above. Vitamin K deficiency of the newborn – A combination of liver immaturity, a sterile gut microbiome and low-quality breast milk makes infants at higher risk of Vitamin K deficiency. This usually presents in days 2-4 of life but can occur up to two months in age, often with unexplained haemorrhage
Vitamin K and warfarin
Warfarin is an anti-coagulant that is used to prevent the risk of thromboembolism in certain patients. Warfarin competitively inhibits Vitamin K epoxide reductase complex 1 (VKORC1), an enzyme essential for the activation of Vitamin K in the body. By preventing the activation of vitamin K, the vitamin K dependent clotting factors (II, VII, IX, X) are inhibited and therefore clotting is inhibited too. Patients taking warfarin are monitoring regularly using a blood test called the International Normalised Ratio (INR). The INR is calculated based on the ratio between the prothrombin times of the test and control samples. It is important to advise patients on warfarin not to eat foods with high levels of Vitamin K as this can increase their INR, and potentially lead to bleeding.
Forms of bilirubin
Bilirubin exists in two forms; unconjugated and conjugated. Unconjugated bilirubin is insoluble in water. This means it can only travel in the bloodstream if bound to albumin and it cannot be directly excreted from the body. In contrast, conjugated bilirubin is water soluble. This allows it to travel through the bloodstream without requiring transport proteins like albumin, which means that it can also be excreted out of the body. In the next section, we will explore the metabolic pathway of bilirubin in more detail
Creation of bilirubin
Reticuloendothelial cells are macrophages which are responsible for the maintenance of the blood, through the destruction of old or abnormal cells. They take up red blood cells and metabolise the haemoglobin present into its individual components; haem and globin. Globin is further broken down into amino acids which are subsequently recycled. Meanwhile, haem is broken down into iron and biliverdin, a process which is catalysed by haem oxygenase. The iron gets recycled, while biliverdin is reduced to create unconjugated bilirubin.
In the bloodstream, unconjugated bilirubin binds to albumin to facilitate its transport to the liver. Once in the liver, glucuronic acid is added to unconjugated bilirubin by the enzyme glucuronyl transferase. This forms conjugated bilirubin, which is soluble. This allows conjugated bilirubin to be excreted into the duodenum in bile.
Once in the colon, colonic bacteria deconjugate bilirubin and convert it into urobilinogen. Around 80% of this urobilinogen is further oxidised by intestinal bacteria and converted to stercobilin and then excreted through faeces. It is stercobilin which gives faeces their colour. Around 20% of the urobilinogen is reabsorbed into the bloodstream as part of the enterohepatic circulation. It is carried to the liver where some is recycled for bile production, while a small percentage reaches the kidneys. Here, it is oxidised further into urobilin and then excreted into the urine
What is jaundice?
Jaundice describes a yellow discolouration of the sclera and/or skin in response to elevated bilirubin levels.
Pre-hepatic jaundice is caused by increased haemolysis. This results in the increased presence of unconjugated bilirubin in the blood as the liver is unable to conjugate it all at the same rate. This is caused by Tropical disease, e.g. malaria, yellow fever Genetic disorders, e.g. sickle-cell anaemia, Gilbert’s syndrome Haemolytic anaemias
Hepatic jaundice is caused by liver impairment. This causes the decreased ability of the liver to conjugate bilirubin, resulting in the presence of conjugated and unconjugated bilirubin in the blood. Liver damage can result from: Viral hepatitis Hepatotoxic drugs, e.g. paracetamol overdose, alcohol abuse
Post-hepatic jaundice is caused by the blockage of bile ducts. This results in backflow of conjugated bilirubin into the blood as it cannot move past the obstruction. Bile duct obstruction can be caused by: Gallstones Hepatic tumours Pancreatic tumours
Gilbert’s syndrome is an inherited disorder where there is hyperbilirubinaemia (excess bilirubin in the bloodstream) due to a fault in the UGT1A1 gene leading to a deficiency in UDP-gluconoryltransferase. This faulty gene results in slower conjugation of bilirubin in the liver and so it builds up in the bloodstream instead of being excreted through the biliary ducts. When well, patients are usually asymptomatic and have normal bilirubin levels. However, under physiological stressors such as illness, alcohol abuse and extreme exercise, patients can become markedly jaundiced.
Carbohydrate metabolism funciton of th eliver
The liver plays a central role in maintaining blood glucose levels. Following consumption of food, excess glucose can be stored within the liver as glycogen. This is stimulated by insulin release. Around 100g of glycogen is stored in the liver (300g is stored in skeletal muscle). This glycogen can then be degraded to release glucose in times of exercise (skeletal muscle stores) or fasting (liver stores). It is important to note that it is not a direct reversal of synthesis. The steps of glycogenolysis are as follows: One residue of glycogen is removed and converted to glucose-1-P by glycogen phosphorylase or de-branching enzyme Glucose-1-P is converted to Glucose-6-P by phosphoglucomutase Glucose-6-P is then converted to Glucose by glucose-6-phosphatase This glucose then enters the bloodstream to be used throughout the body The liver can convert amino acids, lactate, pyruvate and glycerol into glucose too, via gluconeogenesis. Gluconeogenesis is stimulated by cortisol and glucagon, and inhibited by insulin.
Lipogenesis of the liver
Lipogenesis Fatty acids are synthesised within the cytoplasm of hepatocytes from Acetyl-CoA. The reaction requires ATP and NADPH. Firstly, Acetyl-CoA is converted to Malonyl-CoA by acetyl carboxylase. This step is important in the regulation of lipogenesis as it is allosterically activated by citrate and inhibited by AMP. Fatty acid synthase then adds these 2 carbon molecules (malonyl-CoA) to a growing fatty acid. This fatty acid is then linked to a carrier protein. Lipogenesis is stimulated by the presence of insulin and inhibited by glucagon and adrenaline
Lipolysis of the liver
During fasting or stress, fatty acids can be activated in the liver to undergo B-oxidation. This occurs in the mitochondria and produces acetyl-CoA which can either enter the TCA cycle or be used to produce ketone bodies. The long chains of fatty acids are broken down into a series of 2 carbon acetate units, which are then combined with co-enzyme A to form acetyl-CoA. This acetyl-CoA can then be combined with oxaloacetate to form citrate for the beginning of the TCA cycle. Glucagon and adrenaline stimulate the process of lipolysis whereas it is inhibited by insulin
Which proteins are synthesised in the liver?
Protein Synthesis Proteins can be synthesised in the liver using amino acids consumed in the diet. Protein synthesis is stimulated by insulin and growth hormone. The following are synthesised within the liver: Albumin CRP (an infection marker) Blood clotting factors – Factors II, VII, IX and X are Vitamin K dependent Thrombopoietin Angiotensinogen
Which proteins are broken down in the liver?
The liver has an important role in the catabolism of excess amino acids consumed in the diet (i.e amino acids which are not needed for the synthesis of proteins or nitrogen-compounds). They are metabolised in the liver but the amino group is potentially toxic and must be removed. One option is transamination, where the amino group can be transferred to ketoacids through the actions of alanine aminotransferase (ALT) and aspartate aminotransferase (AST): The amino group can be added to alpha-ketoglutarate to form glutamate The amino group can be added to oxaloacetate to form aspartate The amino group can be removed from an amino acid to produce a ketoacid and ammonia, via deamination. This uses high-specificity glutaminase, or low-specificity L+D amino-acid oxidase enzymes. The ammonia is then converted to an ammonium ion, which must be removed due to toxicity. It can be removed via glutamine or the urea cycle
Explain ammonia metabolism
Ammonium ions are produced during amino acid degradation and blood concentration is typically low due to their toxicity. Ammonia is toxic to cells as it reduces TCA cycle activity, affects neurotransmitter synthesis and creates an alkaline pH. Detoxification occurs in two steps, firstly ammonia is used to synthesise glutamine when combined with glutamate. Glutamine can then be used to synthesise nitrogen compounds such as purines and pyramidines. It is either then transported to the kidney, where the ammonia is directly excreted, or to the liver where it is used to make urea. The urea can then also be transported to the kidneys where the ammonia can be directly excreted in urine.
Vitamin metabolism in th eliver
The liver is important in the metabolic activation of Vitamin D. It is carried to the liver in the blood where it is first converted to the prohormone calcifediol via hydroxylation. This calcifediol is then transported to the kidneys where it is converted into calcitriol, the biologically active form of Vitamin D. The conversion of calcifediol to calcitriol is catalysed by 25-hydroxyvitamin D3 1-alpha-hydroxylase. This conversion is stimulated by parathyroid hormone and low calcium
PP of hyperammonaemia and cause
Hyperammonaemia is a metabolic disturbance in which there is an excess of ammonia in the blood. It can be caused by a variety of conditions both congenital and acquired: Genetic defects in enzymes involved in the urea cycle. The urea cycle is important in converting toxic ammonia into urea. 5 major steps are involved, with each having a different enzyme. Any defect in these enzymes can lead to a build up of ammonia in the blood. The main enzymes include; N-acetyl-glutamate synthase, carbamoyl phosphate synthetase , ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinic acid lyase, and arginase. Hepatitis B can increase the likelihood of damage to the hepatocytes and inflammation, increasing the risk of liver cirrhosis. This can lead to increased shunting of blood from the liver to the IVC, reducing the filtration of blood and removal of toxins like nitrogen; hence leading to hyperammonaemia Liver cirrhosis It is potentially a very dangerous condition due to the effects of ammonia on the body and patients often present with vomiting, ataxia, lethargy, weakness, confusion and tachypnoea. If left untreated it may progress to encephalopathy and eventually death
Tx of hyperammonaemia
In severe hyperammonaemia initial treatment should involve haemodialysis to remove excess ammonia. Following this, dietary protein often needs to be reduced and substances such as arginine and sodium benzoate can be given to those patients with enzyme disorders
carbohydrate storage of the liver
Carbohydrate Storage The liver plays a central role in maintaining blood glucose levels. Following consumption of food, excess glucose can be stored within the liver as glycogen. This is stimulated by insulin release. Around 100g of glycogen is stored in the liver (300g is stored in skeletal muscle). The synthesis of glycogen occurs in the following steps: Glucose is converted to Glucose-6-P by glucokinase (hexokinase in skeletal muscle) Glucose-6-P is converted to Glucose-1-P by phosphoglucomutase Glucose-1-P is then converted to UDP-Glucose Finally UDP-glucose is added to the glycogen chain within the liver either by glycogen synthase or branching enzyme
vitamin A storage liver [incl. ut's functions]
Vitamin A Vitamin A is stored within stellate cells in the liver as retinyl ester. The active form, retinol, is converted to this by lecithin:retinol acyltransferase. This provides an easily retrievable source of Vitamin A and regulates its availability for other pathways. Vitamin A may be stored or removed from storage several times a day, regulating the amount in circulation and preventing damage that may occur as a result of excess. This process is known as retinol recycling. The functions of Vitamin A include: Formation of the photoreceptor rhodopsin Signalling molecule within gene transcription Normal function of the immune system Mobilisation of iron stores for red blood cell productio
summarise metabolic function of the liver
carbohydrate metabolims, lipid metabolism, protein metabolism, ammonia metabolism, vitamin metabolism
vitamins stored in the liver
vitamin D storage and function
Vitamin D can either be produced in the body (cholecalciferol) or found in food (ergocalciferol). It must be metabolised in the liver before becoming the active form. Functions of Vitamin D include: Maintaining normal serum calcium and phosphate concentrations Increased absorption of calcium in the kidneys and intestines Increased mobilisation of calcium from bone , activating osteoclasts to release more calcium
Vitamin E is a family containing various chemicals, including anti-oxidants. It can be stored in either the liver or adipose tissue. Functions include: Antioxidant Preventing propagation of free radicals Protects Vitamin A
There are two forms of Vitamin K depending on whether they are obtained from plant or meat sources. The functions of Vitamin K include: Important for synthesis of clotting factors II, VII, IX and X. Co-factor for enzymes
Vitamin B12, cobalamin, is typically found within animal products. Around 2-5mg is stored in the body, with around 50% of this being in the liver. Functions of Vitamin B12 include: Production of DNA and RNA Maintaining healthy neurones Red blood cell production – alongside Vitamin B9
Mineral storage of the liver
Iron Iron levels within the body need to be tightly regulated. Therefore, excess amounts must be stored in places such as the liver. Most iron within cells is stored in ferritin, a protein produced by the liver. All cell types within the liver can store iron however the majority is stored within hepatocytes. In severe iron overload the ferritin storage becomes saturated and so excess becomes stored within haemosiderin. However haemosiderin is a large, insoluble complex and iron stored within it is difficult to mobilise effectively
Glycogen storage diseases
Patients with an inherited deficiency in an enzyme involved in the glycogenolysis pathway may experience episodes of hypoglycaemia. Cori disease (glycogen debranching enzyme deficiency) and Von Gierke disease (glucose-6-phosphate enzyme deficiency) are types of glycogen storage diseases. Children may present with an enlarged liver, due to excessive glycogen storage.
Physiology jaundice Cx
Serious and very serious genetic jaundice effects?
GIlbert's - low UGT enzyme to convert UCB-> CB - maximum 6 UGT mol/min Cragler Nagglar - no UGT -> very dangerous -> kernicterus