Tuesday [abdomen cavity, liver physiology, hernias]

Question 1

Where is Calot’s triangle located?

Answer 1

Porta hepatis of the liver [where the hepatic ducts and neurovascular structures enter/exit the liver]

Question 2

What are the border’s of Calot’s trinalge?

Answer 2

• medial = common hepatic duct - inferior = cystic duct - superior = inferior surface of the liver

Question 3

Annotate Calot’s borders

Answer 3

Question 4

Contents of Calot’s triangle

Answer 4

• 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

Question 5

What is a laraproscopic cholecystecomy procedure and why is Calot’s trinalge relevant to this?

Answer 5

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.

Question 6

Borders of the inguinal triangle

Answer 6

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

Question 7

Contents of the inguinal triangle

Answer 7

Other than the layers of the abdominal wall, the inguinal triangle does not contain any structures of clinical importance.

Question 8

What does the inguinal triangle demarcate?

Answer 8

However, the triangle does demarcate an area of potential weakness in the abdominal wall – through which herniation of the abdominal contents can occur

Question 9

Annotate contents of the inguinal triangle

Answer 9

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Question 10

Define a hernia

Answer 10

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.

Question 11

What is a direct inguinal hernia?

Answer 11

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

Question 12

What is an indirect inguinal hernia?

Answer 12

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

Question 13

Define these types of hernias

Answer 13

Question 14

What is the peritoneal cavity?

Answer 14

Potential space between teh parietal and visceral peritoneum.

Question 15

What does the peritoneal cavity contain?

Answer 15

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)

Question 16

Peritoneal cavity

Answer 16

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Question 17

Greater sac divided by what?

Answer 17

Transverse colon

Question 18

How is the greater sac subdivided?

Answer 18

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

Question 19

How are the supra and infra-colic compartments connected?

Answer 19

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.

Question 20

Greater sac

Answer 20

Question 21

What are subphrenic abscesses?

Answer 21

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.

Question 22

Where do subphrenic abscesses typically occur?

Answer 22

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).

Question 23

Where does the lesser sac [omental bursa] lie?

Answer 23

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

Question 24

How is the omental bursa connected to the greater sac?

Answer 24

The omental bursa is connected with the greater sac through an opening in the omental bursa – the epiploic foramen (of Winslow)

Question 25

Where is the epiploic forman located?

Answer 25

The epiploic foramen is situated posterior to the free edge of the lesser omentum (the hepatoduodenal ligament)

Question 26

annotate

Answer 26

Question 27

annotate

Answer 27

Question 28

Peritoneal cavity in males image

Answer 28

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Question 29

Peritoneal cavity in females

Answer 29

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

Question 30

Is the peritoneal cavity closed in females? Why so/not so?

Answer 30

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)

Question 31

Are infections common in the peritoneal cavity?

Answer 31

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.

Question 32

annotate

Answer 32

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Question 33

Explain the two times peritoneal fluid is sampled [culdocentesis and paracentesis]

Answer 33

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.

Question 34

Causes and CF of ascites

Answer 34

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.

Question 35

Causes and CF of peritonitis

Answer 35

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.

Question 36

Explain the parietal peritoneum [incl, where it’s derived from, nervous supply etc.]

Answer 36

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

Question 37

What is the peritoneum made up of?

Answer 37

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

Question 38

Nervous supply, dermatomes, derivates of the visceral peritoneum

Answer 38

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

Question 39

Cause and Cx of peritoneal adhesions

Answer 39

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.

Question 40

Give examples of intraperitoneal organs

Answer 40

Intraperitoneal organs are enveloped by visceral peritoneum, which covers the organ both anteriorly and posteriorly. Examples include the stomach, liver and spleen

Question 41

Main way of dividing the retroperitoneal organs

Answer 41

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

Question 42

Useful mnemonic for recalling abdominal viscera

Answer 42

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

Question 43

annotate

Answer 43

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Question 44

What is the mesentery?

Answer 44

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.

Question 45

What is th eomentum?

Answer 45

The omenta are sheets of visceral peritoneum that extend from the stomach and proximal part of the duodenum to other abdominal organs.

Question 46

Distinguish between the greater and lesser omentum

Answer 46

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).

Question 47

annotate

Answer 47

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Question 48

What are the peritoneal ligaments?

Answer 48

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.

Question 49

Three main areas of viseceral localised pain

Answer 49

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.

Question 50

Where may retroperitoneal organ pain and irritation to the diaphragm present?

Answer 50

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.

Question 51

How may appendicitis present as referred pain?

Answer 51

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.

Question 52

Annotate

Answer 52

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Question 53

development of the inguinal canal

Answer 53

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.

Question 54

Where is the mid-inguinal point and the midpoint of the inguinal ligament

Answer 54

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Question 55

Wall boundaries of the inguinal canal

Answer 55

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

Question 56

During periods of intra-abdominla pressure, how is herniation prevented?

Answer 56

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

Question 57

What are the two rings in the inguinal canal?

Answer 57

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.

Question 58

COntents of the inguinal canal

Answer 58

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

Question 59

What happens during an inguinal hernia?

Answer 59

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..

Question 60

Three types of vitamin K

Answer 60

Vitamin K can be categorised into three main types: Phylloquinone (Vitamin K1), Menaquinone (Vitamin K2) and artificially synthesised Vitamin K

Question 61

Properties of vitamin K

Answer 61

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.

Question 62

Synthesis of vitamin K

Answer 62

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

Question 63

Function fo vitamin K

Answer 63

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.

Question 64

Causes of vitamin K deficiency

Answer 64

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

Question 65

Vitamin K and warfarin

Answer 65

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.

Question 66

Forms of bilirubin

Answer 66

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

Question 67

Creation of bilirubin

Answer 67

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.

Question 68

Bilirubin conjugation

Answer 68

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.

Question 69

Bilirubin excretion

Answer 69

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

Question 70

What is jaundice?

Answer 70

Jaundice describes a yellow discolouration of the sclera and/or skin in response to elevated bilirubin levels.

Question 71

pre-hepatic jaundice

Answer 71

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

Question 72

hepatic jaundice

Answer 72

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

Question 73

Post-hepatic jaundice

Answer 73

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

Question 74

Gilbert’s syndrome

Answer 74

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.

Question 75

Carbohydrate metabolism funciton of th eliver

Answer 75

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.

Question 76

Lipogenesis of the liver

Answer 76

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

Question 77

Lipolysis of the liver

Answer 77

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

Question 78

Which proteins are synthesised in the liver?

Answer 78

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

Question 79

Which proteins are broken down in the liver?

Answer 79

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

Question 80

Explain ammonia metabolism

Answer 80

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.

Question 81

Vitamin metabolism in th eliver

Answer 81

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

Question 82

PP of hyperammonaemia and cause

Answer 82

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

Question 83

Tx of hyperammonaemia

Answer 83

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

Question 84

carbohydrate storage of the liver

Answer 84

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

Question 85

vitamin A storage liver [incl. ut’s functions]

Answer 85

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

Question 86

summarise metabolic function of the liver

Answer 86

carbohydrate metabolims, lipid metabolism, protein metabolism, ammonia metabolism, vitamin metabolism

Question 87

vitamins stored in the liver

Answer 87

ADEK

Question 88

vitamin D storage and function

Answer 88

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

Question 89

vitamin E

Answer 89

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

Question 90

vitamin K

Answer 90

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

Question 91

vitamin B12

Answer 91

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

Question 92

Mineral storage of the liver

Answer 92

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

Question 93

Glycogen storage diseases

Answer 93

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.

Question 94

Physiology jaundice Cx

Answer 94

kernicterus

Question 95

Serious and very serious genetic jaundice effects?

Answer 95

GIlbert’s - low UGT enzyme to convert UCB-> CB - maximum 6 UGT mol/min Cragler Nagglar - no UGT -> very dangerous -> kernicterus