MB ChB Year 1: Nutrition and Energy

WORK SESSION 8: Liver and Pancreas

AIMS

To understand some physiological functions of the exocrine pancreas, liver and gall bladder, and their disturbance in some gastro-intestinal diseases. To appreciate the wide variety of acute abdominal conditions, and the difficulties that might be associated with differential diagnosis.

OBJECTIVES

On successful completion of this exercise you will:

Be able to describe the anatomy, histology and functions of the liver, pancreas and gall bladder in healthy people.
Understand the formation of bile and the enterohepatic circulation of bile salts.
Distinguish between haemolytic, cholestatic and hepatocellular jaundice.
Understand some of the nutritional and genetic factors that pre-dispose patients to hepatobiliary and pancreatic disease.
Be able to list at least seven conditions that might give rise to an acute abdomen.
Appreciate the utility of MRI, CT and ultrasound scans, enzyme assays, antibody tests and blood chemistry measurements for diagnostic purposes.

You should complete all parts of the exercise before the tutorial. Part A is a self-directed exercise. Interactive self assessment exercises will allow you to check your answers. Part B will be discussed during the tutorial.

The purpose of these pages is to allow you to check any answers that you are uncertain of. It is NOT intended that you check every answer, or that you use these resources to complete the work session material - both these approaches would be enormously time-consuming, and probably teach you very little. Please use the resources selectively, and return to them for revision later.

PREPARATION FOR THIS SESSION

Before these case studies you should:

Consult the sources of information recommended below.
Complete the exercises in the INTRODUCTION.
Consider the following two cases, and answer the questions before you attend the tutorials. The process is important: if you merely copy the answers from a friend then you won't engage sufficiently with the material. Find the answers for yourself.

Some useful sources of information
Canadian Society of Intestinal Research	These leaflets are available via the web and contain accurate but basic information aimed at the general public. You should know most of this material before the exams, but the leaflets on each disease are very similar and you don't need to read them all.
patient leaflets on pancreatitis from NIDDK and CORE
patient leaflets on gallstones from NIDDK and CORE
Kumar & Clarke "Clinical Medicine" 6th edition (2005) pages 340 - 345: Acute abdomen pages 349 - 352: Liver functions pages 358 - 361: Jaundice pages 398 - 405: Gallbladder pages 408 - 414: Pancreatitis	These are mainstream text books that we expect you to consult when attempting this exercise. Please remember to use the glossary and the index if there are words you don't understand. You will also need your histology text book.
Tortora and Grabowski "Principles of Anatomy & Physiology" 9th edition (2000) chapter 24
Nelson & Cox "Lehninger Principles of Biochemistry" 4th edition (2005) chapters 17 & 21.
Gaw et al "Clinical Biochemistry" 2nd edition (1998) pages 50-53: liver function tests and jaundice	These are some alternative text books that you might prefer in place of our recommended ones.
Tierney et al "Current Medical Diagnosis & Treatment" 40th edn (2000) chapter 15
Murray et al "Harper's Biochemistry" 25th edn (2000) Chapters 28, 34 & 55
Haslett et al "Davidson's Principles and Practice of Medicine" 18th edition (1999) pages 684 - 693
Interactive case challenge - gallstones	This is supplementary material. Don't try to memorise these reports which are all available via the web. Shop around for recent articles that you find interesting and fun to read.
Medscape Interactive case challenge - pancreatitis
Medscape Article on gallstone complications

We suggest that you read these documents online, and write your answers in the printed workbook. The Medscape case studies differ from the examples in this workbook.

INTRODUCTION

Review the histology of the liver and the human biliary tree using Wheater's Functional Histology and the micrographs on the module website. Which disease of the biliary tree is characterised by anti-mitochondrial antibodies, and which mitochondrial enzyme are these antibodies commonly directed against? [Either identify the disease using a text book index, or search the Web of Science database for a recent review on the subject. This is a useful transferable skill, so ask the library help desk if you don't know how to do it. You should know of this disease, but don't spend a lot of time on it. Find the relevant multi-enzyme complex on your metabolic flowchart.]
Sketch the histology of a liver lobule, and explain which fluid is flowing where. [You should have two inputs and three outputs.] See Dr Whittle's lecture notes, or Tortora & Grabowski , page 844.
Are all the liver cells the same, and if not, how are they specialised?

Examine the light microscope sections of human liver tissue below, and identify the various structures marked. These slides have been stained with H&E and first image was photographed at low magnification:

The second image was photographed at higher magnification:

Structural features	Identification
1. Structure "A" (note the walls and any neighbouring structures)
2. Structure "B" (observe the spatial relationships)
3. Structure "C" (examine at the overall shape)
4. Structure "D" (study the size of the lumen and the wall thickness)
5. Structure "E" (note the extremely delicate walls)
6. Structure "F" (note the characteristic appearance of the walls)
7. Structure "G" (note the shape and location of this component)
8. Structure "H" (look at the size and the wall thickness)

feedback options:

CASE STUDIES: PART A

Two patients were seen as emergencies around 2:30am. Both of them were suffering from severe abdominal pain.

Patient 1 was a Muslim cleric aged fifty one. He said his pain had started gradually after lunch, and at first he thought it might be severe indigestion because it was most intense around his stomach, although he found it difficult to identify the precise spot. He constantly shifted his position in an attempt to find relief. He described the pain as sharp and stabbing, going right through to his back. It was present all the time, but it was worse when he was lying down. He had vomited repeatedly, but that did not ease the pain. He was now retching ineffectually and producing only small quantities of a clear greenish fluid, free from blood. He had no history of indigestion and could not remember having this pain before. On examination his abdomen was tense and distended, and extremely tender over a broad area. His temperature was 38.5°C, BP 90/60, pulse 130/min, weak but regular, respirations 30/min, lungs clear, height 1.8m, weight 73kg. Bowel sounds were faint. He had not noticed any changes in his bowel habits, and did not drink alcohol for religious reasons.

Patient 2 was a night club manageress, aged 38 who had been taken ill at work. She said she had suffered previously from similar pains provoked by heavy meals. "Its usually fish and chips, doctor. I know they're not good for me, but I'm afraid I can't resist 'em. I've never been as bad as this before." She did not drink alcohol when working. On examination she was tense and sweating and her upper abdomen was extremely tender. Her temperature was 39°C, BP 120/80, pulse 115/min and regular, respirations 20/min, lungs clear, height 1.6m, weight 82 kg. Bowel sounds were noticeable. The whites of her eyes were distinctly yellow, and she had noticed on previous occasions that her faeces were a pale clay colour and her urine was unusually dark. She was worried about child-care arrangements if hospital treatment were prolonged. She vomited once in radiology and said that she now felt slightly better.

Plain chest X-rays showed nothing unusual in either case. See patient 2 below:

Plain chest X-rays taken with the patient standing may be useful in the diagnosis of a perforated ulcer, when gas may be visible under the diaphragm, as shown in the example below:

Remember that neither of today's patients showed any abnormality on a plain chest X-ray.

Blood samples were taken from both patients for electrolyte measurements and a battery of enzyme tests. The results from abdominal CT and ultrasound are shown below. (We view these images looking from the feet towards the head.)

normal control

CT scan: patient 1

Trace or sketch the CT images above and identify the spinal cord, vertebrae, ribs, diaphragm, liver, gall bladder, portal vein, pancreas, aorta, inferior vena cava, kidney, colon, ileum, stomach and spleen.

Which level in the spinal column would you normally associate with each of the following structures? (This is not very exact because some viscera are mobile: use your anatomy text book or the visible human material if you need to check.)

anatomical structures	vertebral body
1. gastro-oesophageal junction
2. duodenum
3. aortic arch
4. ileo-caecal junction
5. urinary bladder (empty)
6. the CT section shown for both patients above

feedback options:

patient 2 ultrasound

dilated ducts no stones

Gallstone images from another patient were obtained using magnetic resonance equipment. They show stones in the gall bladder, and good images of the biliary tree. With MRI it is easy to change the plane of the section and view the image in any desired orientation. The first image shows stones in the gall bladder, and a dilated common bile duct.

Remember that all these images have the patient's right on your left and the transverse sections are viewed from the feet looking towards the head. Notice the different pattern of light and dark areas on these magnetic resonance images when compared with the older CT pictures and the ultrasound scans. In particular, bones appear dark on MRI scans, but they are bright on conventional X-rays and CT.

Comparing diagnostic techniques

Imaging technique:	plain X-rays	CT scans	ultrasound	MRI scans
Advantages: low cost see gases see gut lumen see solid viscera see cholesterol stones view images in any plane easy interpretation of images	1 2 3 4 5 6 7	8 9 10 11 12 13 14	15 16 17 18 19 20 21	22 23 24 25 26 27 28
Disadvantages: expensive at present radiation dose to patient can't see cholesterol stones images are difficult to interpret	29 30 31 32	33 34 35 36	37 38 39 40	41 42 43 44

feedback options:

The technician who centrifuged the blood samples noticed some obvious differences between the supernatant fractions from the two patients. Why do these samples look different in the following picture?

Review the results from the laboratory tests and the patients' other symptoms and explain their most probable diagnostic or prognostic significance. Point at the names with the mouse for additional details of the laboratory tests.

measurement and normal range	patient one	conclusion	patient two	conclusion
haematocrit 37%-47%	58%	01	39%	02
haemoglobin 12.0-16.0 g/dL	19.0 g/dL	03	12.4 g/dL	04
urea nitrogen 2.2-7.7 mmol/L	6.7 mmol/L	05	4.3 mmol/L	06
white cell count 4.8-10.8 × 10³	15.6 x 10³	07	13.3 × 10³	08
plasma albumin 37-49 g/L	57 g/L	09	37 g/L	10
" ALP 70-300 U/L	88 U/L	11	398 U/L	12
" ALT 10-50 U/L	28 U/L	13	160 U/L	14
" amylase <109 U/L	1022 U/L	15	210 U/L	16
" AST 15-45 U/L	48 U/L	17	190 U/L	18
" bicarbonate 22-30 mmol/L	23 mmol/L	19	22 mmol/L	20
" bilirubin (total) 3-15 mmol/L	14 mmol/L	21	106 mmol/L	22
" calcium 2.1-2.6 mmol/L	1.8 mmol/L	23	2.2 mmol/L	24
" chloride 95-105 mmol/L	101 mmol/L	25	100 mmol/L	26
" cholesterol 4.9-6.7 mmol/L	20 mmol/L	27	6.3 mmol/L	28
" creatinine 70-120 mmol/L	112 mmol/L	29	72 mmol/L	30
" GGT 5-45 U/L	220 U/L	31	205 U/L	32
" glucose 3.5-5.7 mmol/L	10.5 mmol/L	33	5.0 mmol/L	34
" lipase 56-240 U/L	5562 U/L	35	690 U/L	36
" potassium 3.5-5.0 mmol/L	4.2 mmol/L	37	4 mmol/L	38
" sodium 135-145 mmol/L	150 mmol/L	39	132 mmol/L	40
" triglycerides <2.3 mmol/L	59 mmol/L	41	1.6 mmol/L	42

symptoms	patient one	suspicion	patient two	suspicion
pain	gradually worsens	43	sudden onset and relief	44
temperature	38.5ºC	45	39ºC	46
B.P. & pulse	90/60; 130/min	47	120/80; 115/min	48
BMI	work it out	49	work it out	50
bleeding / CXR	none / normal	51	none / normal	52
vomiting	continuous	53	once	54
urine	not known	55	darkens	56
scans	see above	57	see above	58
blood plasma	cloudy	59	yellow	60
sclera	normal	61	yellow	62
alcohol intake	none	63	moderate	64

feedback options:

Which of these results are the most informative, and why?

Patient 1 was treated initially with nasogastric suction, pethidine and a saline drip. Nothing was given by mouth, and this patient eventually required parenteral feeding. His condition gradually improved and he was discharged from hospital three weeks later. Long term therapy required gemfibrozil, and the patient was advised to eat a reduced calorie diet low in saturated fat and high in wholegrain cereals, root and leafy vegetables, pulses and legumes.

Justify each element in the therapy for Patient 1:

Therapy	Justification
1. Nasogastric suction?
2. Pethidine not codeine for analgesia? (The benefits are disputed.)
3. Fluid and electrolytes? (saline drip)
4. Parenteral feeding? (The benefits are disputed. Enteral feeding may be better.)
5. Gemfibrozil?
6. Special diet?

feedback options:

Only about 10% of these cases arise through the mechanism identified above. What are the two most common causes of this complaint, and why are they unlikely in this case?

Patient 2 improved quickly and discharged herself from hospital later the same morning to attend to her children. She was re-admitted for elective surgery in the following week. Review the anatomy of the liver, duodenum and pancreas. What surgical treatment might be appropriate for Patient 2?

List five common clinical conditions, other than the two already identified above, that might also give rise to severe abdominal pain, requiring emergency treatment.

CASE STUDIES: PART B

Refer to the biochemical test results for the two patients.

Two enzymes are particularly important for the diagnosis of pancreatitis. Why do you suppose that they are used?
List the principal classes of enzymes secreted by the pancreas. Why are some of them produced with a "safety catch" when others are not?
Which hormones are particularly relevant to the functioning of the gallbladder and exocrine pancreas? Where are these hormones produced and what else do they do?
What is the pH optimum for most pancreatic enzymes secreted into the gut? Sketch the ultrastructure of a pancreatic acinar cell, and briefly describe how the various pancreatic secretions are produced.
What is the major component in most gallstones? Draw its "carbon skeleton". Where does it come from, where in the body does it principally occur (give two examples) and what are its ultimate fates?
The biosynthetic pathway for cholesterol involves an enzyme HMG-CoA reductase that is inhibited by the "statins" which are an important class of drugs. Complete the following diagram which shows the chemical reaction catalysed by HMG-CoA reductase. In which part of which cell is this enzyme located? How is it regulated in the short term and over longer periods?
Many important hormones are derived from this chemical family. Name four major hormone groups and describe where these compounds are made.

The "bile salts" are ultimately derived from the same group of compounds. Sketch the main structural features of one such chemical found in bile. How does this chemical structure help in the digestion of fats?
How exactly do bile salts get into the bile? How many times would a typical bile salt molecule traverse this route each day?
Briefly review the functions of the liver under four main headings: (1) intermediary metabolism, (2) formation and secretion of bile, (3) synthesis of blood components, (4) detoxication reactions.

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