Sunday, 31 July 2016

LOVE STORY


Love Story is romantic and funny yet 

tragic

Love Story 

              is romantic and funny yet tragic. It is the tale of two college students whose love enables them to overcome the adversities they encounter in life: Oliver Barrett IV, a Harvard jock and heir to the Barrett fortune and legacy, and Jennifer Cavilleri, the quick-witted daughter of a Rhode Island baker. Oliver (Ollie) was expected to assume control of his father's business empire, while Jennifer (Jenny), a music major studying at Radcliffe College planning to study in Paris. From very different worlds, Oliver and Jenny are immediately attracted to each other and their love deepens. The story of Jenny and Ollie is a story of two young people who come from two separate worlds and are joined together in the unlikeliest of ways.
Upon graduation from college, the two decide to marry, against the wishes of Oliver's father, who promptly severs all ties with his son. Without financial support, the couple struggles to pay Oliver's way through Harvard's Law School, with Jenny working as a private school teacher. Graduating third in his class, Oliver gets several job offers and takes up a position at a respectable New York law firm. Jenny promises to follow Oliver anywhere on the East Coast. The couple move to New York City, excited to spend more time together, rather than working and studying. With Oliver's new income, the pair decide to have a child. After Jenny fails to conceive, they consult a medical specialist, who after repeated tests, informs Oliver and Jenny that Jenny is suffering from leukemia and will not be able to live longer than a few months.
As instructed by his doctor, Oliver attempts to live a normal life without telling Jenny of her condition. Jenny nevertheless discovers her ailment after confronting her doctor about her recent illness. With their days together numbered, Jenny begins a costly cancer therapy, and Oliver soon becomes unable to afford the multiplying hospital expenses. Desperate, he seeks financial relief from his father. Instead of telling his father what the money is truly for, Oliver misleads him. From her hospital bed, Jenny speaks with her father about funeral arrangements, and then asks for Oliver. She tells him to avoid blaming himself, and asks him to embrace her tightly before she dies. When Mr.Barrett realizes that Jenny is ill and that his son borrowed the money for her, he immediately sets out for New York. By the time he reaches the hospital, Jenny dies. Mr. Barrett apologizes to his son, who replies with something Jenny had once told him: "Love means not ever having to say you're sorry..." and breaks down in his arms.

Sources

It is sometimes said that Al Gore falsely claimed that the plot is based on his life at Harvard. In fact, Al Gore mentioned, correctly, that he had read that the characters were based on him and his wife. In 1997 Segal confirmed Gore's account, explaining that he had been inaccurately quoted in the Nashville Tennessean and that "only the emotional family baggage of the romantic hero... was inspired by a young Al Gore. But it was Gore's Harvard roommate, Tommy Lee Jones, who inspired the half of the character that was a sensitive stud, a macho athlete with the heart of a poet". Erich Segal had met both Mr. Jones and Mr. Gore at Harvard in 1968, when he was there on sabbatical.[2] Despite these claims, the book is essentially an updating of The Lady of the Camellias by Alexandre Dumas, fils, which was also the basis of Giuseppe Verdi's opera La traviata.

Thursday, 28 July 2016

URINE ANALYSIS-NORMAL AND ABNORMAL FINDINGS)




URINE ANALYSIS-NORMAL AND ABNORMAL FINDINGS)

Definitions
·         Urinalysis is the examination of urine based on normal and abnormal findings.
·         Polyuria is the passage of large volume of urine in a given period.
·         Haemoglobinuria is the presence of haemoglobin in urine.
·         Haematuria is the presence of red blood cells in urine.
·         Oliguria Reduced output volume of urine (below 500mls) can be caused by acute nephritis, fever, perspiration.
·         Anuria is the stoppage of urine output.
·         Urochrome is the chemical component that give the normal colour of urine.
·         Glycosuria is the passage of glucose in urine
·         Proteinuria is the passage of protein in urine
·         Ketonuria is a medical condition in which ketone bodies are present in the urine.

Mention the constituents of urine 
·                  Water 95% Electrolyte (Sodium, Potassium, Magnesium, Chloride, and Bicarbonate).
·         Protein – It can be found in the urine of person with urinary schistosomiasis, UTI, Nephrotic syndrome, renal disease, pregnant women.
·         Glucose – It can be found in diabetic patient.
·         Ketones – It can be found in untreated diabetic patient or starvation.
·         Bilirubin – It can be found in a patient with hepatocellular jaundice or cholestatic (obstructive jaundice).
·         Urobilinogen – Increase amount can be found in severe haemolysis
·         Nitrite – Can be found in patient with UTI.
·         Blood – Can be found in urinary schistosomiasis, bacteria infection acute Glomerularnephritis, sickle cell disease, calculi.
·         Specific gravity – Normal relative density ranges from 1.002 – 1.050 depending on the state of hydration of the person. Its proportional based on urea and sodium concentration.In renal failure the ability of the kidney to concentrate and dilute urine is reduced.
·         Usually high relative mass density can be found when the urine contains glucose,proteins or other heavy particles
Cells
·         Blood cells – Normal erythrocyte 0-3/high power field.
·         Large number indicates infection, trauma, renal tumour or renal calculi.
·         Normal Leucocytes: 0 – 5/high power field. Large numbers indicate infection e.g UTI.
·         Yeast cells – Suggestive candidiasis.More predominant in diabetic,pregnant women,or obesity.
Crystals
·         Triple phosphate crystals appers in alkaline urine which suggestive to renal calculi.
·         Calcium crystals appears in acidic urine which suggestive to renal strictures.
·         Cholesterol crystals suggestive to be severe UTI,Nephritis,rupture in lymph drainage in thoracic.
·         Leucine/Tyrosin suggestive to be severe liver disease.
·         Uric acid can be increased in gout,malignat lymphoma,fever or leukaemia.
Casts
·         Hyaline cast indicate damage of glomerular filter membrane, strenuous exercise or fever.
·         Granular cast indicate renal damage.
·         Cellular cast suggestive to be pyelonephritis or Glomerularnephritis,severe injury to glomerular,bacterial infection ,endocarditis or septicaemia
Parasites 
·         Trophozoite of Trichomonas vaginalis which appears in dancing movement indicates that the patient suffered from Trichomoniasis
·         Filarial worms:-microfiralial larva can be seen moving across microscopic field
·         Schistosome haematobium ova can be observed under microscope with terminal spine structure ,it indicates URINARY SCISTOSOMIASIS

 List significance of each constituent 
·         Protein: to diagnose and monitor proteinuria e.g in pregnancy or nephritic syndrome
·         Glucose: to screen for and monitor glucose intolerance such as in Diabetes mellitus
·         Bilirubirin: to assist in the diagnosiss of hepatocellular and obstructive jaundice
·         Urobilinogen: To investigate jaundice
·         Ketones:-To detect and monitor ketonuria eg in Diabetes
·         Haemoglobin:-To investigate intravascular haemolysis, microbial infection and glomerular nephritis
·         Nitrite and leucocyte esterase:-To assist in the diagnosis of Urinary tract infection
·         Specific gravity:-To investigate the concentrating and diluting powder of kidney

Describe the characteristics of urine 
·         Physical examination
·         Determination of chemical compositions
·         Microscopic examination
Physical examination
§  The examination can be done using naked eyes which includes appearance, measuring volume for 24 hourly urine.
§  Colour: Normal appearance of urine pale yellow due to chemical compound know as urochrome. It should be clear or only slightly hazy.
§  Physical Appearance (colour and clarity) of urine can be altered in many conditions
§  Urinary tract infection –Urine appear cloudy due to pus cells and bacteria
§  Urinary schistosomiasis-urine appear red and cloud because it contain blood (haematuria)
§  Haemoglobinuria (black water fever) – urine appear brown and cloudy because it contain free haemoglobin.
§  Jaundice – Urine appear yellow brown or green brown because it contain bile pigments or increase amount of urobilin (oxidized urobilinogen)
§  Bancroftian filariasis Urine appears milky – whitish, because it contains chyle.
Volume
·         Normal volume urine output excreted per day is 1.0 - 2.0L.
·         Abnormal output can be:-
·         Polyuria – That is increase output volume of urine, can be caused by; diabetic patient, excessive fluid intake.
·         Oliguria – Reduced output volume of urine (below 500mls) can be caused by acute nephritis, fever, perspiration.
·         Anuria – Stoppage of urine output, can be caused by intravascular haemolysis, severe UTI, renal stricture BPH (benign prostate hypotrophy), impaired blood circulation.

 Identify normal and abnormal urine 
           

      
Image 1
This is budding yeast.
Normal chemical compositions of urine
·         The composition of urine depends on diet and cellular metabolic activities of the body.
·         In health it contains water 95%, Electrolyte (Sodium, Potassium, Magnesium, Chloride, and Bicarbonate).
·         Waste products (Urea, Uric acid, Creatinine,) acids and alkali in buffered form.
·         The normal pH reaction of freshly passed urine is around 6.0
Abnormal chemical components in urine
·         Protein – It can be found in the urine of person with urinary schistosomiasis, UTI, Nephrotic syndrome, renal disease, pregnant women.
·         Glucose – It can be found in Diabetes mellitus patient.
·         Ketones – It can be found in untreated diabetic patient or starvation.
·         Bilirubin – It can be found in a patient with hepatocellular jaundice or cholestatic (obstructive jaundice).
·         Urobilinogen – Increase amount can be found in severe haemolysis
·         Nitrite – Can be found in patient with UTI.
·         Blood – Can be found in urinary schistosomiasis, bacteria infection acute Glomerularnephritis, sickle cell disease, calculi.
·         Specific gravity – Normal relative density ranges from 1.002 – 1.050 depending on the state of hydration of the person. Its proportional based on urea and sodium concentration.In renal failure the ability of the kidney to concentrate and dilute urine is reduced.
·         Usually high relative mass density can be found when the urine contains glucose,proteins or other heavy particles
Cells
·         Blood cells – Normal erythrocyte 0-3/high power field.
·         Large number indicates infection, trauma, renal tumour or renal calculi.
·         Normal Leucocytes: 0 – 5/high power field. Large numbers indicate infection e.g UTI.
·         Yeast cells – Suggestive candidiasis. More predominant in diabetic, pregnant women, or obesity.

 
 WBCs and one RBC in the urine 

Crystals
·         Triple phosphate crystals appears in alkaline urine which suggestive to renal calculi.
·         Calcium crystals appears in acidic urine which suggestive to renal strictures.
·         Cholesterol crystals suggestive to be severe UTI,Nephritis, rupture in lymph drainage in thoraxic.
·         Leucine/Tyrosine suggestive to be severe liver disease.
·         Uric acid can be increased in gout, malignant lymphoma, fever or leukaemia.
Casts
·         Hyaline cast indicate damage of glomerular filter membrane, strenuous exercise or fever.
·         Granular cast indicate renal damage.
·         Cellular cast suggestive to be pyelonephritis or Glomerularnephritis, severe injury to glomerular, bacterial infection ,endocarditis or septicaemia
This picture shows hyaline casts in the urine viewed 40X microscopically. (Picture by ASCP)

HYALIN CAST

Parasites 
Trophozoite of Trichomonas vaginalis which appears in dancing movement indicates that the patient presence of haemoglobin in urine.
·         Haematuria is the presence of red blood cells in urine.
·         Oliguria Reduced output volume of urine (below 500mls) can be caused by acute nephritis, fever, perspiration.
·         Anuria is the stoppage of urine output.
·         Urochrome is the chemical component that give the normal colour of urine.
·         Glycosuria is the passage of glucose in urine
·         Proteinuria is the passage of protein in urine
·         Ketonuria is a medical condition in which ketone bodies are present in the urine.
Physical examination
§  The examination can be done using necked eyes which includes appearance, measuring volume for 24 hourly urine.
§  Colour: Normal appearance of urine pale yellow due to chemical compound know as urochrome.
Appearance of urine can be altered in many conditions:
§  Urine when appears cloudy can be due to pus cells and bacteria of urinary tract infection
§  Urine when appears red and cloud could be due to Urinary schistosomiasis-

Evaluation

What do you understand by the following terms?
·         Urinalysis,
·         Polyuria
·         Haemoglobinuria
·          Haematuria
·         Oliguria
·         Anuria
·         Glycosuria
·         Proteinuria
·         Urochrome
List the clinical significance of performing urinalysis.
Explain abnormalities found in urine, especially RBCs, WBCs, protein, glucose and ketones.

 References.
·         Carl A. Burtis et al, 2008,Fundamental of Clinical Chemistry,Six Edition,Saunders.
·         Ramnik Sood,2006,Medical Laboratory Technology,First Edition,Jintendar P Vij.
·         Monica Cheesbrough,2009, District Laboratory Practice in Practice in Tropical Coutries,Second Edition,Cambrige University Press.
·         Robert K. Murray (1990): Harper’s Biochemistry; 22nd Edition Prentice – Hall International Inc.
·         Carl A. Burtis (2001): Fundamental of clinical chemistry, 15th Edit W.B.Saunders Company.
·         Wendy Anerson 2007): Clinical Chemistry; Larboratory PerspectiveF.E.Davis Company.

ELEMENTARY STRUCTURE AND FUNCTIONS OF HUMAN BODY.



ELEMENTARY STRUCTURE AND FUNCTIONS OF HUMAN BODY. 


Define the following Terms 




·   Definitions 

         Metabolism is the processes of the human body that provides energy, interconvert chemicals (requiring or providing energy) and help to carry out functions
         Catabolism: degradation process that often produces energy or waste products
         Anabolism: synthesis of new biochemicals for use in the body; often requires energy

          Liver is the dark red organ in the upper part of the abdomen on the right side just beneath the diaphragm.
         Bilirubin is the orange yellow pigment derived from the catabolism (break down) of haemoglobin
         Jaundice is a yellow discoloration of the skin, sclerae (whites of the eyes) and mucus membranes caused by hyperbilirubinemia.
Other definitions:
·         Reticulo Endothelial System is a body defence system that consists variety of types of cells that have the ability to engulf or phagocytize substances such as foreign particles which include Liver, Bone marrow and Spleen
·         Biliverdin is a green bile pigment formed by catabolism of haemoglobin and is converted into bilirubin in the liver.
·         Haemoglobin is the iron containing protein attached to the red blood cells that transports oxygen from the lungs to rest of the body.
·         Unconjugated Bilirubin is free bilirubin that has not been conjugated with glucuronic acid.
·         Conjugated Bilirubin is bilirubin that has been taken up by liver cell and conjugated to form water solube bilirubin diglucuronide.
·         Urobilinogen is colourless compound formed in the intestine by the reduction of bilirubin.
·         Stercolinogen is a bilirubin metabolite and procursor of Stercobilin formed by the reduction of Urobilinogen
  • Pre-hepatic jaundice is a condition in which a person’s skin and whites of the eyes are discoloured yellow due to an increased rate of haemolysis (breakdown of red blood cells). 
  • Hepatic jaundice is a condition in which a person’s skin and whites of the eyes are discoloured yellow due to injury or disease of the Liver cells.
  • Post-hepatic jaundice a condition in which a person’s skin and whites of the eyes are discoloured yellow due to biliary obstruction (obstruction of the bile flow). It is also called obstructive jaundice.
  • Hyperbilirubinemia is increased levels of bilirubin in the blood 
  • Porphyrin is an organic compound that contains four pyrrole rings.
  • Pyrrole rins A porphyrin is an organic compound that contains four pyrrole rings. is a pentagon-shaped ring of four carbon atoms with a nitrogen atom at one corner (C4H5N).
  • Icteric is relating to or affected with jaundice.
  • Conjugation is a chemical reaction to add a molecule often to make a water soluble product.
  • Oxidation is the addition of H+ sometimes in the presence of oxidation to increase the oxidation state of a molecule while Reduction is removing of H+ and addition of e- to decrease the oxidation state.
·         Hepatocyte: liver cells; the main site where liver function occurs
·         Biliary: pertaining to bile ducts or tubes draining bile away from the liver
·         Kupfer cells: immune defence cells in the liver






questions
What is Bilirubin metabolism?
Give students two minutes to discuss in pairs



Answer: bilirubin metabolism is the end result of chemical reactions to degrade haeme from red blood cells to form conjugated bilirubin and reduce to urobilinogen to be easily excreted in faeces and urine.

Introduction to Bilirubin metabolism
         An overview of the Liver
         Bilirubin is mainly formed from the breakdown of haemoglobin in Reiculoendothelial cells of the Liver, Spleen and Bone marrow.

The structure and function of the liver 

         Liver is the biggest and the most complex organ in the body with more than 500 functions. It lies immediately under the diaphragm, occupying most of the upper right part of the abdomen.
         The liver is an "incredible major chemical and metabolic factory” in the human body,  producing many important chemical compounds needed to survive, such as bile, albumin, blood clotting factors, cholesterol, Vitamin E. Converts amino acids (proteins) and Plays a major role in maintaining normal blood sugar levels, an important source of energy for the brain, heart and muscles
The Structure.
         The Liver is the largest gland in the body, i.e. In adults the liver weighs 2% of body mass.
         Occupying the greater part the upper abdomen.
         The liver is divided into right and left lobes by fossae for the gallbladder and the inferior vena cava. The right lobe of liver is the largest lobe, whereas the left lobe of liver is smaller wedge-shaped. The quadrate and caudate lobes are described as arising from the right lobe of liver, but functionally are distinct these are seen on the posterior side of the liver making it to have four lobes.

                    

                               Macroscopic Structure of the Liver

Functions:
         Eliminates various harmful chemicals from the body (remove or process alcohol, poisons and toxins). Treats about 1,300 ml of blood per minute, thereby acting as the body's "garbage disposal.
         Performs numerous other functions such as regulating lipids or metabolizing prescribed and over the counter drugs, alcohol, and many other ingested chemicals such as caffeine, etc.  
         Making bile which passes from the liver to the gut and helps to digest fats.
         Helping to process fats and proteins from digested food and urea formation.
         Storing glycogen (fuel for the body) which is made from sugars. When required, glycogen is broken down into glucose which is released into the bloodstream.
         Synthesis, esterification and excretion of Cholesterol.
         Regulation of blood volume and immune mechanisms.
         Because about 1.3 to 1.5 liters of blood, passes in the liver within a minute, the liver is recognized as the blood enriched organ.
         Making proteins that are essential for blood to clot (clotting factors).
         The functional unit of the liver is the lobule
·         There are three major types of cells in the liver, the hepatocytes, the biliary epithelial cells and the Kupffer cells.
·         Liver lobules are hexagonal in outline and are formed by cubical-shaped cells; the hepatocytes arranged in pair, between them are columns of cells called sinusoids. Hepatic macrophages (Kupffer cells) are also present which function in destroy and ingest worn out cells and foreign particles in the liver.
·         A central vein is in the centre of each lobule. Central veins unite to form hepatic veins, which exit the liver on its posterior and superior surface and empty into the inferior vena cava.
·         Hepatic cord radiate out from the central vein of each lobule like the spokes of a wheel. The hepatic cords are composed of hepatocytes, the functional cells of the liver. The spaces between the hepatic cords are blood channels called hepatic sinusoids. The sinusoids are lined with a very thin, irregular squamous epithelium consisting of two cell populations; Endothelial cells and Hepatic phagocytic cells (kupffer cells).
·         A cleft-like lumen, the bile canaliculus lie between the cells within each cord
·         Canaliculi are small bile ducts that connect to larger bile ducts and ultimately the common bile duct for flow of bile to the duodenum, small intestine.


                                       
                             

The function of the hepatocytes
The hepatocytes carries the metabolic functions and are responsible for;
  • Bile production including bilirubin
  • Storage of nutrients, vitamins, iron and copper
  • Interconversion of nutrients (proteins, carbohydrates, fats, ketones)
  • Detoxication of drugs and deamination of amino acids and ammonia forming urea
  • Phargocytosis
  • Sythesis of blood components  and coagulation factors ( haematopoiesis in foetal liver)

 Structure and function of Gallbladder 

Structure of Gallbladder
·         The gallbladder is a pear-shaped sac lying on the visceral surface of the right lobe of the liver in a fossa between the right and quadrate lobes. It is about 8 cm long and 4 cm wide
·         The gallbladder has the following structures:
o   A rounded end (fundus of gallbladder), which may project from the inferior border of the liver,
o   A major part in the fossa (body of gallbladder), which may be against the transverse colon and the superior part of the duodenum;
o   A narrow part (neck of gallbladder) with mucosal folds forming the spiral fold.
The walls of the gallbladder is formed by three tunics which are
·         Inner mucous layer which folded into reggae and this allows it to expand.
·         The muscular layer which contains smooth muscles that allows the gallbladder to contract
·         The outer covering layer of the serosa
Function of the gallbladder;
·         It stores and concentrates the bile which is secreted by the liver
·         Concentration of the bile by up to 10 or 15 fold by absorption of water through the walls of the gall bladder
·         Release of stored bile
·         Gallbladder receives many small vessels from hepatic bed and cystic arteries a branch of right hepatic artery
·         Venous drainage is through the multiple small veins from the gallbladder bed.




 Organisation of the Biliary System 
·         Is the duct system for the passage of bile extends from the liver, connects with the gallbladder, and empties into the descending part of the duodenum. The connection of ducts begins in the liver parenchyma and continues until the right and left hepatic ducts are formed. These drain the respective lobes of the liver.
·         The two hepatic ducts combine to form the common hepatic duct, which runs, near the liver, with the hepatic artery proper and portal vein.
·         As the common hepatic duct continues to descend, it is joined by the cystic duct from the gallbladder. This completes the formation of the bile duct.
·         The bile duct continues to descend, passing posteriorly to the superior part of the duodenum before joining with the pancreatic duct to enter the descending part of the duodenum at the major duodenal papilla
·         Therefore the bile either empties directly into the duodenum or is diverted for minutes up to several hours through the cystic duct into the gallbladder,
·         The clinical importance of this system is if there is a tumour of the head of pancreas will cause obstruction to the bile duct and cause a condition known as obstructive jaundice.


Bile Production, Circulation and Functions

 

Bilirubin Metabolic Pathway from Haeme Molecule (tetrapyrole
Metabolism incudes
      Anabolism  (synthesis))
      Catabolism  (degradation)
Pathway is the steps to achieve metabolism
Tetra = 4

Haemoglobin Degradation
Bilirubin pathway: Haem degradation
      Within  cells of the reticuloendothelial system (i.e., phagocytes) in spleen
      Breakdown in haem proteins results in  daily supply of bilirubin
      Most from haemoglobin in aged RBCs (~75%)
      Remaining (15-20%) from destruction of RBC precursors in bone marrow, turnover of haemoproteins in other tissues



Bilirubin Formation:  Biliverdin is an intermediate product. Biliverdin: Green pigment; reduced to Bilirubin
questions
Give students two minutes to discuss in pairs one of the two questions. Where is biliverdin formed? Why is bilirubin bound to albumin?



Answer:  Biliverdin is formed in the reticulo-endothelial system such as spleen.
Answer Bilirubin is bound to albumin because it is lipophilic and hydrophobic so not water soluble unless bound to albumin for transport in blood.

Bilirubin



      Yellow-orange pigment (tetrapyrole)
      Major waste product of haeme metabolism
      Photoisomers exist
      Normal state; hydrophobic/lipophilic so transported bound to plasma proteins
      Cis form: upon exposure to light; more hydrophilic
      Secreted directly into bile for excretion without further modification so basis of phototherapy
Bilirubin Transport & Further Metabolism:
Transported to liver (from spleen) bound to albumin and when released in liver, it enters hepatocyte
On the smooth ER, it is conjugated with glucoronic acid with the enzyme (UDP-glucoronyl transferase) forming -> Mono- and di- glucoronide conjugates

Question : What are the components of the reaction to conjugate bilirubin?
(Work in pairs and have present their answer.)
Answer: Summary of Bilirubin Conjugation
Bilirubin  + Glucoronic acid  -------(UDP-glucoronyl transferase)à
Bilirubin diglucoronide and Bilirubin monoglucoronide

Bilirubin metabolism in Small Intestine:
“Conjugated” bilirubin secreted by the hepatocytes into the biliary canaliculi (small bile ducts connecting to larger bile ducts)
Bilirubin is reduced by anaerobic bacteria  in the gut to

Forms of urobilinogens (3 colorless tetrapyrroles) which are
     Stercobilinogen
     Mesobilinogen
     Urobilinogen:
Oxidized to bile pigments found in faeces to:  Stercobilin, mesobilin, urobilin

Question What forms of bilirubin are found in blood and in urine? (Work in pairs and then they present their answers.)
Answer: Forms of Bilirubin
Blood (Serum):
     Total (unconjugated and conjugated)
     Direct (conjugated)
Urine
     Direct (conjugated)
     Water soluble form


·         The liver produces in the hepatocytes and secretes a large amount of bile each day into the bile ducts. Continuous bile formation is an important function of the liver, and bile is used as a vehicle for the secretion of bile acids
·         Bile salts are quantitatively the major constituents of bile and are circulated in the enterohepatic circulation between the liver and the small intestine with high efficiency.
·         Synthesis of bile acids is a major route of cholesterol metabolism. Bile is synthesised through a series of chemical reactions in hepatocytes then secreted into minute bile canaliculi that originate between the hepatic cells. The mechanisms involved in the transcellularmovement of bile salts across hepatocytes is poorly understood
·         Half of the cholesterol produced in the body is used for bile acid synthesis.
·         90% of excreted bile acids are reabsorbed by active transport in the ileum and recycled in what is referred to as the enterohepatic circulation which moves the bile salts from the intestinal system back to the liver and the gallbladder.
·         Clinical significance is, since bile acids are made from endogenous cholesterol, the enterohepatic circulation of bile acids may be disrupted to lower cholesterol.  Gall stones form when there is a problem with synthesis or excretion of bile and they are mostly formed from cholesterol.

·         Bile constitutes of water, mineral salts, mucous, bile pigment (bilirubin), bile salts which are derived from the primary bile acids and cholesterol
·         Bile serves as a means for excretion of several important waste products from the blood. These include especially bilirubin, an end product of haemoglobin destruction, and excesses of cholesterol.

Types and Causes of Hyperbilirubinaemia 


3. questions:
·      What is kernicterus? 
·      What urine and serum bilirubin results are expected in hepatitis? 
·      What urine and serum bilirubin results are expected in gall stones?


 Answer:  Kernicterus is encephalopathy (disorder of the brain) related to increased bilirubin that leads to permanent brain damage

Answer: In hepatitis you expect to see Increased urine bilirubin, Increased total and direct serum bilirubin and Indirect bilirubin and direct serum bilirubin are both elevated

Answer: gall stones are post –hepatic so you expectedto see Increased urine bilirubin.
In a complete obstruction, urobilinogen is absent from the urine but urinalysis methods may not detect decreased urobilinogen levels

Types of Jaundice:
1.      Haemolytic jaundice (Pre hepatic)
2.      Hepatic jaundice (Intra hepatic jaundice)
3.      Obstructive jaundice (Post hepatic jaundice)
Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects. The three categories are:
         Pre-hepatic jaundice (Haemolytic jaundice): The pathology is occurring prior the liver
         Hepatic (Non obstructive hepatic jaundice): The pathology is located within the liver
         Post-Hepatic (Obstructive jaundice): The pathology is located after the conjugation of bilirubin in the liver

1.0 Pre-hepatic jaundice (Haemolytic jaundice):
         The word “pre-hepatic” would mean “before the liver”. Indeed, pre-hepatic jaundice has nothing to do with the liver. The liver is fine.  The problem has to do with excessive bilirubin production as a result of hemolysis - undue destruction of red blood cells. As mentioned above, bilirubin is derived from hemoglobin contained in red blood cells. The spleen and liver constantly monitor the circulation, removing old, damaged, or abnormal red blood cells from the circulation.
         If the liver and spleen remove too many red blood cells from the circulation, too much bilirubin will be produced.  The liver will shift into overdrive, removing as much of the bilirubin as it can.
         Eventually, the liver’s capacity to remove this excessive amount of bilirubin is exceeded, and bilirubin levels build up in the bloodstream, staining the tissues yellow.  Serum bilirubin would be increased from normal due to unconjugated bilirubin but urine bilirubin should be negative and urobilinogen increased.

2.0 Hepatic jaundice (Intrahepatic Jaundice)
      Hereditary
        Gilbert’s syndrome (Small increase in unconjugated bilirubin)
     due to decreased hepatic uptake and
     due to decreased conjugation
      Secondary
     Interference of uptake in liver by drugs
      Acetominophen, Paracetamol, alcohol
     Or Infection
      Viral Hepatitis
     Reduced Excretion of Hepatic Bilirubin (Excretion into bile is rate-limiting step) and may be caused by hepatocellular damage
     Leads to increase in conjugated bilirubin
     Uptake and conjugation in liver is also effected
     Increase in unconjugated bilirubin
      Secondary causes include:
      cirrhosis, hepatitis, cholestasis induced by synthetic steroids.
Serum total and conjugated bilirubin would be increased as would urine bilirubin and urobilinogen.

3.0  Posthepatic Jaundice (Obstructive jaundice)
     Caused by an obstruction of the biliary tree such as gall Stones and cancer of liver or pancreas
      Increased Conjugated bilirubin
     other biliary metabolites, (bile acids) accumulate
     Hyperbilirubinemia is proportional to obstruction
      Characterized by pale colored stools, dark urine due to high amounts of urine bilirubin but negative urobilinogen.  Serum bilirubin would be increased from normal and mostly conjugated bilirubin.


Jaundice is the Yellow coloration of sclera, skin resulting from increased serum bilirubin levels (25-50mg/L) [hyperbilirubinemia] while  Icterus is the yellow colouration of serum or urine.

·         Gilbert disease: hereditary intrahepatic jaundice due to due to decreased hepatic uptake and decreased conjugation
·         Non haemolytic jaundice, it is failure of bilirubin trasportation  from sinusoid membrane to microsome region
·         Criger – najar disease.  It is adificiency of UDP- glucolonyl Transferase
·         Dubin Johnson. It is intrahepatic cholestasis which is caused by viral hepatitis,toxic cirrhosis and necrosis

Key Points 

          Liver is the dark red organ in the upper part of the abdomen on the right side just beneath the diaphragm.
·          Biliverdin is a green bile pigment formed by catabolism of haemoglobin and is converted into bilirubin in the liver.
·         Bilirubin is the orange yellow pigment derived from the catabolism (break down) of haemoglobin
·         Unconjugated Bilirubin is free bilirubin that has not been conjugated with glucuronic acid.
·         Conjugated Bilirubin is bilirubin that has been taken up by liver cell and conjugated to form water soluble bilirubin diglucuronide.
·         Urobilinogen is colourless compound formed in the intestine by the reduction of bilirubin.
·         Jaundice is a yellow discoloration of the skin, sclerae (whites of the eyes) and mucus membranes caused by hyperbilirubinemia.

  • Pre-hepatic jaundice is a condition in which a person’s skin and whites of the eyes are discoloured yellow due to an increased rate of haemolysis (breakdown of red blood cells). 
  • Hepatic jaundice is a condition in which a person’s skin and whites of the eyes are discoloured yellow due to injury or disease of the Liver cells.
  • Post-hepatic jaundice a condition in which a person’s skin and whites of the eyes are discoloured yellow due to biliary obstruction (obstruction of the bile flow). It is also called obstructive jaundice.
  • Hyperbilirubinaemia is increased levels of bilirubin in the blood 
  • Conjugation is a chemical reaction to add a molecule often to make a water soluble product.
  • Oxidation is the addition of H+ sometimes in the presence of oxidation to increase the oxidation state of a molecule while Reduction is removing of H+ and addition of e- to decrease the oxidation state

  • Bilirubin is a waste product of haemoglobin and is water insoluble until conjugated in the liver hepatocytes.
  • Conjugated bilirubin is reduced to urobilinogen in intestines and is excreted in faeces and urine.
  • Hyperbilirubinemia causes jaundice and icteric serum and urine and is due to pre-hepatic, intrahepatic or post-hepatic disorders.
  • Measuring bilirubin forms in serum and measuring urine bilirubin and urobilinogen can help to determine source or cause.

Evaluation

Describe What you understand by the following terms.
         Reticulo Endothelial System
         Metabolism
         Catabolism
         Anabolism
          Liver
          Stercolinogen
          Biliverdin
          Bilirubin
          Haemoglobin
          Unconjugated Bilirubin
          Conjugated Bilirubin
          Urobilinogen
         Jaundice, Pre hepatic jaundice, Hepatic jaundice, Posthepatic jaundice, Hyperbilirubinemia,  Porphyrins, Icteric
         Describe the functional unit of the liver (lobule)
         List the function of the hepatocytes
         Explain bile production, circulation and functions
         Explain structure and function of gall bladder
         Describe the metabolism of haemoglobin  to biliverdin and then unconjugated bilirubin
         Describe the transport and metabolism of unconjugated bilirubin to conjugated bilirubin including enzyme reaction

         Describe the transport of conjugated bilirubin to urobilinogen