Endogenous Pathway of Lipoprotein Metabolism (June 2018)

In an integrated curriculum, which our Medical School deploys, temporal distribution of related topics can be an issue which may seriously affect students' learning. This problem can go unnoticed by both lecturers and students. It is a worry when scheduling related topics far apart. They would be close together in a conventional curriculum.


Let me give you an example of what I mean.

1. The topic Exogenous Pathway of Lipoprotein Metabolism was covered in two ways - guided self-learning (GSL5) and a class lecture. However, these two inputs were spaced far apart on the time-table.
2. The GSL5 module was made available to students at the e-learning portal on 21 Sept 2017
3. The lecture Lipoprotein Metabolism was delivered in the lecture hall on 28 February 2018
4. Time difference between GSL5 and the lipoprotein lecture was 5 months plus 1 week
5. A semester exam was conducted on 25 June 2018 (9 months after GSL5 and 4 months after the lipoprotein lecture)

Module:
CELL AND TISSUE
COURSE (GMT 101)
PHASE I MD 2017/2018
GUIDED SELF-LEARNING (GSL) ON
STRUCTURE AND FUNCTION OF LIPIDS
Prepared by
PROF. FARIDAH ABDUL RASHID
DEPARTMENT OF CHEMICAL PATHOLOGY
SCHOOL OF MEDICAL SCIENCES
KUBANG KERIAN, KELANTAN
Updated on
11 September 2017
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Medical Doctor (MD) Programme Phase I
Academic Session 2017/2018
Cell & Tissue Course (GMT 101)
Week 2
GSL 5: Structure and Function of Carbohydrates, Lipids, Amino Acids
and Nucleic Acids (Biomolecules) ... uploaded at e-learning portal
KNSS, IZA, FAR
21 Sept 2017
Contents:
PLASMA LIPOPROTEINS (page 6)

1, Describe the structure and function of plasma lipoproteins.
2. Describe the exogenous pathway of plasma lipoprotein metabolism.
3. Describe the endogenous pathway of plasma lipoprotein metabolism.
4. Describe reverse cholesterol transport.
5. Describe how lipids can cause heart disease.

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Phase I
Year 1 Sem 2
MEDICAL DOCTOR (MD) PROGRAMME PHASE I (YEAR 1)
Academic Session 2017/2018
CVS Course (GMT 107)
Week 3
Lecture
Lipoprotein Metabolism
28 February 2018

Even though the lecture on Lipoprotein Metabolism was given late in first year (Sem 2), in the CVS Course (GMT 107), it should not be an excuse for students who are unable to connect with or recall earlier topics (Learning Issues, LI, or Learning Objects, LO).

Students may not be able to recall or connect that the same topic and essay questions have appeared earlier - in the self-learning module or guided self-learning (GSL), in their first week of Medical School (Sem 1, Cell & Tissue Course (GMT 101).

This shows that students often do not revise, re-study or check back on what they have learned very early in their medical course. There is a gap and topics early in their medical studies may have been forgotten altogether. However, they only need to revise, re-study or check back. They may not be able to connect past topics if they did not re-check, revise or re-study the topics that they have learned many months before to exam.

There are 3 possible essay questions concerning the topic Lipoprotein Metabolism. Any of these 3 essay questions can pop up on any exam - Term and Professional. Therefore, students should be aware that there are these 3 options. They should be prepared, rather than not be aware and be unprepared or go blank during exam.

For June 2018 exam, though half the students passed (73/134 or 54%), I am quite disappointed that quite a large number of students (61/134 or 46%) still failed a repeat essay question on lipoprotein metabolism, which had been made available to students in their first week of Medical School since 2014 (and even earlier). What a shame!

The essay question below was taken directly from GSL5, that was made available online on the e-learning portal on 21 Sept 2017, to all incoming first-year medical students. Students either saw it but overlooked it, or took it seriously, studied and attempted to answer it! There is no excuse for failing this essay question.


Essay
Describe the endogenous pathway of lipoprotein metabolism. (10 marks)

How often has this question been used?
This question has been used repeatedly since 2014.

Proposed Model Answer

(i) Diagram

Is a diagram required?
No and it is not necessary.
A diagram is not required since it is not specifically asked.
However, you can draw a labelled diagram or flowchart if it helps and guides you to answer the question.
Refer to any diagram on "endogenous pathway of lipoprotein metabolism" in any textbook or Google it. 

Be careful when drawing for an essay question. You can use simple ball and arrow diagram and label everything using abbreviations. But students often go wrong here because they cannot recall the lipoprotein abbreviations correctly, and which way the LDL cascade should go. Many remember it wrongly. There are 3 distinct pathways of lipoprotein metabolism, and they do not merge. Be extra careful. 

(ii) Text

	Any 10 Statements pertaining to the following, or other statements relevant to the topic.	Max. 10 Marks
1.	Endogenous pathway happens all the time.	1
2.	It involves VLDL-LDL metabolism or “LDL cascade” and LDL receptor-mediated uptake in liver.	1
	Synthesis of VLDL:
3.	The liver synthesizes VLDL. Hepatocytes release nascent VLDL into the Space of Disse àVLDL enter sinusoids à VLDL enter systemic circulation.	1
	VLDL have several fates:
4.	a)      VLDL transport triglycerides from liver to peripheral tissues for utilization.	1
5.	b)      When VLDL reach vascular/capillary beds, they undergo hydrolysis (lipolysis) by LPL where their triglycerides contents are hydrolysed to free fatty acids (FFAs) and glycerol.	1
6.	c)      VLDL remnants are taken up by liver via LDL (B,E) receptors.	1
7.	d)     The VLDL are reduced in size (but increased density) and are converted into VLDL remnants and IDL, as a result of lipoprotein lipase (LPL) activity, hydrolysis or delipidation, which requires apolipoprotein C-II as cofactor.	1
	Unesterified FFAs have several fates:
8.	a)      During lipolysis, some FFA can be carried by plasma albumin and dispersed in plasma for delivery to other cells. Not much of this happens.	1
9.	b)      Normally, FFA can enter underlying adipocytes by simple diffusion. Inside the adipocytes, the FFA are re-esterified to form triglycerides (TG) once more. Adipocytes store TG until required (as an energy source during fasting or starvation). A majority of FFA are stored in adipocytes following lipolysis.	1
10.	c)      In times of starvation, when blood glucose is low and glycogen reserves are low, triglycerides stored in adipose tissues are hydrolysed by hormone sensitive lipase (HSL) and the FFAs are released from adipose tissue. FFAs then attach to circulating albumin and are brought to liver for beta-oxidation, for continued energy supply.	1
	IDL have several fates:
11.	a)      IDL can be converted into LDL by LPL in blood (intravascular).	1
12.	b)      IDL can be taken up by hepatic receptors.	1
13.	c)      IDL can be converted into LDL by hepatic lipase (HTGL) in liver.	1
	LDL have several fates:
14.	a)      Normally, LDL are taken up by hepatic LDL (B,E) receptors. The contents of LDL are broken down into FC, CE, PL, TG/ DG/ MG/ FFA and amino acids. These are kept within the hepatocytes or recycled for use by other cells. Hepatic contents of FC and CE are regulated by acyl cholesterol acyltransferase (ACAT). Few things can happen if cholesterol is low, specifically in the cell or in the blood. If there is low cellular FC, stored cholesterol (as cholesteryl ester, CE) is broken down to free cholesterol (FC) by ACAT. If there is low plasma FC, the liver cell makes more FC via increased HMG-CoA reductase activity. The 2 enzymes, ACAT and HMG-CoA reductase, are sensitive to cellular and blood cholesterol levels, and combined, they regulate cholesterol levels in cells and blood.	1
15.	b)      LDL can also deliver its contents directly to cells, eg adrenal glands, for synthesis of steroid hormones.	1
16.	c)      Under abnormal levels of LDL in the blood (eg hyperlipidaemia), LDL can be taken up by the scavenger receptors present on extrahepatic tissues (EHT).	1
17.	d)     LDL apoB-100 will be oxidized due to the prolonged presence of LDL in blood. Also, the LDL particle is now smaller and apoB-100 is unstable at this stage. ApoB-100 becomes easily oxidised. Oxidised apoB-100 has higher affinity for macrophages. Thus, oxidised LDL will be taken up by macrophages in EHT.	1
18.	e)      Macrophages contain scavenger receptors on their surface. Macrophages are present on blood vessel walls. Oxidised LDL will attach to the receptors and be internalised by macrophages.	1
19.	f)       The oxidised LDL are hydrolysed into component cholesterol, fatty acids, glycerol and amino acids, which are stored within the macrophages.	1
20.	g)      This uptake of oxidised LDL is unregulated (ie, uncontrolled). The macrophages take up as much LDL as they can until they stop functioning and die - becoming foam cells.	1

OUTCOMES

Students' English proficiency

1. Some can write well
2. A few cannot write correct English sentences and seemed to struggle
3. Not knowing how to properly use some words in sentences makes it difficult to comprehend what students are writing or trying to convey. Use of certain words seem difficult for students: constituent, composition, comprise, compose; retained, remained, degrade, bind, combine, uptake, consumed, utilised, undergo, etc
4. Understanding of reciprocal relationships - lipoprotein density increases as size decreases
5. Practice will make essay writing perfect, but there is lack of written assignments in first-year Medical School.
6. There may be greater underlying problems such as learning the relevant science subjects in Bahasa Malaysia in primary and secondary schools. Subjects such as Biology, Chemistry, Physics, may have been taught in Bahasa. They should be taught in English if students have to master English at university level, and especially in a medical course.
7. Students have tried their best to answer in English.

Students' answering difficulties

1. No schema or outline to use to answer the question
2. Careless writing 
3. Haphazard writing 
4. Don't know how & where to begin
5. No proper writing style
6. Page improperly utilised
7. Considerable amount of scribbling at edges
8. Diagrams in pencil and not ink 
9. Thinking and writing at full speed 
10. No knowledge to even write anything
11. Blank or stuck
12. Unexpected essay question
13. No time to check answers

Students' handwriting

• Handwriting was terrible for a majority of the scripts.
• Most handwriting were tiny and had to be read close-up.
• 1 script was intelligible (hard to read and comprehend)

Students' creativity

• Abbreviations for VLDL, IDL and LDL were various and incorrect
• Swapped functions of LDL and HDL
• New abbreviations for lipoproteins were created!  
• New terminologies were created! 
• One student wrote on ADP and ATP

Diagrams drawn by students

• Interesting diagrams, but some were incomplete or wrong
• There were a few little diagrams of sorts. 

PROBLEMS FACED BY STUDENTS
26 students (19.4%) scored 0 marks in June 2018

Breakdown of problems faced by students who scored 0 marks:

• 18 students handed in empty answer scripts (completely no answer; nothing written).
• 1 student answered: formation of Chylomicron (with a smiley) [False]
• 1 student answered wrongly on Chylomicron Metabolism [Chylomicron Metabolism is Exogenous pathway of lipoprotein metabolism.]
• 1 student wrote: In endogenous pathway, lipoprotein is metabolised into chylomicrons. [False. This never happens!]
• 2 students wrote on Bile Metabolism / Cholesterol Synthesis and HMG-CoA [wrong answers]
• 2 students wrote on Lipid Digestion / Micelles and Chylomicron / Stomach Functions and Chylomicron [wrong answers]
• 1 student wrote: Lipoprotein mechanism is breakdown of lipoprotein into amino acids. [False]

FOCUS of this essay question

Since this essay question is specifically about VLDL-IDL-LDL metabolism or endogenous pathway, any answer on chylomicron metabolism or exogenous pathway will be incorrect. Since HDL metabolism is not asked, there is no need to touch on HDL metabolism, except its associated role in the endogenous pathway.

Other answers such as stomach contents and functions, lipid digestion (formation of micelles, enzymic digesiton of lipids), lipid absorption, formation of chylomicron in enterocytes, passage of chylomicron from lacteals via lymphatics to liver are all irrelevant.

Other processes in the liver such as cholesterol synthesis are irrelevant as this question is specific and focused on the metabolism of lipoproteins containing apo B-100.


FALSE Statements

1. This VLDL is major transported [transporter?] of cholesterol [False].
2. LDL send the phospholipid to cell for cell integrity or to the cell that uses it for the production of energy [False].
3. VLDL is the major transporter of cholesterol from adipose tissues [False]. 
4. Lipoproteins are used to generate energy. [False]
5. Endogenous pathway of lipoprotein metabolism is metabolism of chylomicrons [False].

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IRRELEVANT Answers

The essay question specifically asked about endogenous pathway (VLDL-IDL-LDL metabolism), which occurs all the time in the body, whether we are fasting or not. There is no need to write about other topics. There is no need to write about carbohydrate metabolism (polysaccharide digestion, glucose and rbc metabolism). There is no need to write about GIT (stomach contents and functions). There is no need to write about lipid digestion and absorption (bile, lipases, micelles, lacteals) Stay focussed on the topic.

(a) Glucose & rbc metabolism

1. Glucose is converted into pyruvate which will form the cholesterol.
2. When rbc is damaged, or aged, lipoprotein will metabolised to be store into the body as a source of heat, membrane fluidity.

(b) Lipid digestion and absorption 

1. So lipoprotein metabolism functions to break down lipid and protein to their respective basic units for better absorption.
2. Lipid is broken down to its simplest form which are fatty acids and 3 glycerols with the help of ADH for energy.
3. Lipid will enter lacteals (specialised lymph in the villi) to be utilised by the body again (as chylomicra).

(c) Carbohydrate digestion 

1. From complex polysaccharide, it is broken down into disaccharide by removal of water. Then disscharide is broken down to amino acids which is the simplest form of protein.

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Student Answers on

ENDOGENOUS PATHWAY OF LIPOPROTEIN METABOLISM

[F] = False statement

[?] = examiner's query

(a) Students' understanding of the different lipoprotein pathways

1. There are 2 pathway(s) involved in lipoprotein mechanism which are through endogenous pathway and exogenous pathway
2. Endogenous pathway is about VLDL
3. Endogenous pathway of lipoprotein is when it is synthesis from cholesterol inside the liver.
4. Endogenous Pathway is occur within circulation. Endogenous Pathway of lipoprotein metabolism consist of VLDL-LDL metabolism, LDL metabolism and LDL-mediated receptor (uptake).

(b) Ambiguous statements written by students

1. Lipoprotein metabolism occur in liver. It is combination of lipid and protein.[Abstract writing!]
2. Cholesterol is transported from the GIT to the liver in both estercifed [esterified] and free form in the liver. [Meaning?]
3. Cholesterol under go oxidation estirification and compannded with protiens Apo proteins to form lipoproteins which are sent to the bloodstream as VLDL. [Meaning?]

(c) Lipoprotein structure

1. Lipid basic structure and triglyceride and fatty acids
2. For proteins, its amino acids
3. Cholesterol combines with apolipoprotein
4. Cholesterol, apolipoprotein, phospholipid and triglyceride will form VLDL and also empty HDL
5. Lipoprotein is constituent of both lipid and protein.
6. Triglyceride has about 60% in VLDL [This is better written as VLDL contains approximately 60% triglycerides.]
7. VLDL has Apo B-100 molecule [This is better written as Each VLDL has an apo B-100 molecule.]
8. IDL is high in cholesterol

(d) Classes of lipoproteins

1. There are 2 lipoprotein(s) that (are) present in (the) body which are high density lipoprotein (HDL) and low density lipoprotein (LDL). [False] [There are 4 major classes of lipoproteins.]
2. The last one is HDL(?)

(e) Function of lipoproteins

1. LDL is described as bad cholesterol
2. LDL is major transporter of cholesterol. It send the cholesterol (to) the cell of adipose and liver to be stored.
3. HDL is described as good cholesterol
4. The function of HDL is to transport excess cholesterol to the liver to be metabolised. The HDL is the could be recycle for the next  use.

(f) Lipoprotein conversions

1. In lipoprotein metabolism, chylomicron is converted into very low density lipoprotein (VLDL) [F]. VLDL in then convert into intermediate low density lipoprotein (ILDL) [F]. ILDL will form low density lipoprotein (LDL) which then converted into high density lipoprotein (HDL) [F].
2. Chylomicron will bind to Apo E and C to become high density lipoprotein [F]. Then it become  intermediate density lipoprotein, low density lipoprotein and very low density lipoprotein [F]. 
3. After the VLDL will converted into IDL or LDL
4. Triglyceride in VLDL is further dehydrolysed leads to conversion of VLDL to IDL.
5. Very low density lipoprotein (VLDL) is degraded by IDL [F]. [VLDL is degraded by LPL to IDL.] Then, forming Low density lipoprotein (LDL) and exocytosed [endocytosed?] either via (scavenger) receptor-mediated or via hepatic (receptors). Then, LDL is taken up to the hepatocytes [taken up by hepatocytes?]. LDL converted to free cholesterol in liver.

(g) Lipoprotein movements

1. Lipid (from circulation) will flow into the liver to (be) metabolised.
2. VLDL will transport cholesterol from tissue to liver for excretion and HDL will transport cholesterol from liver to tissue [F]. [What does VLDL transport?]
3. When it enters the blood circulation, VLDL attaches to Apo C and Apo E
4. Upon entering the circulation, Apo CII activates lipoprotein lipase (LPL). Lipoprotein lipase hydrolyses triglyceride into free fatty acid and glycerol
5. IDL is taken up by the hepatic cells. This is because hepatic cell recognise Apo E on IDL. Apo C and Apo E is retained from IDL [retained with IDL?]. IDL is hydrolysed [to what?]

(h) Products of lipoprotein hydrolysis by LPL

1. Free fatty acid is used for energy, milk lactating
2. Glycerol is needed in glucogenesis and gluconeogenesis

(i) Lipoprotein uptake

1. Macrophages engulfing lipoprotein becomes foam cell

(j) Depth of students' understanding of the topic asked

1. LDL is low density lipoprotein which collects cholesterol from liver to body
2. HDL is good cholesterol which collects cholesterol from body to the liver
3. Liver will produce VLDL with attachment of Apolipoprotein B-100 which is produced by hepatocyte
4. VLDL will combine with Apo E and Apo CII
5. CII will activate lipoprotein lipase to breakdown triglyceride into fatty acid and glycerol
6. Fatty acid can be used in synthesis of lipid, energy storage, production of milk fat in mammary gland
7. The breakdown of triglyceride reduce the VLDL into IDL (VLDL remnant)
8. IDL will transport into the hepatocyte by binding of Apo E on the surface of liver (LDL receptor)
9. IDL will also degrade into LDL with the help of HTL (hepato ... lipase) [HTL or HTGL is hepatic triglyceride lipase.]
10. LDL is more dense and reduce in size [Meaning?] [LDL is smaller and denser than IDL.]
11. It contain more cholesteryl ester
12. LDL can enter the liver by binding of Apo B-100 at the LDL receptor. [Meaning?] [Where is apo B-100 located?] [LDL apo B-100 binds to LDL receptors present on hepatocytes. OR LDL binds to LDL receptors via its apo B-100.]

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CORRECT answers attempted by students (10 marks)
Text only. Associated diagrams are not included here.

Example 1

1. VLDL (very low density lipoprotein) is synthesized in the liver and consist of triglycerides and Apo B-100. [F] [VLDL contains 4 lipid classes and apo B-100.]
2. Then, VLDL is goes out of the liver into blood circulation.
3. Inside the circulation, it receives two apolipoprotein from HDL which is apo C and apo E.
4. Then, VLDL is hydrolysed by lipoprotein lipase which hydrolyse the triglycerides in(to) fatty acids and monoglycerides.
5. This make VLDL size and density decrease [F].[VLDL size is reduced, but its density increases after lipolysis by LPL.]
6. Before transported back into liver, apo C return back to HDL and VLDL remnants diffuse into liver by lipoprotein receptor and by endocytosis. [Diffuse into liver or taken up by liver?]
7. The VLDL remnants become IDL but IDL does not remain for a long time before it converted into LDL (low density lipoprotein). [IDL exists transiently in blood.]

Example 2

1. VLDL (very light density lipoprotein) is form(ed) endogenously in liver. 
2. It consist(s) of free amino acid, cholesterol, cholesteryl ester, phospholipid, triacylglycerol and apo B-100. [VLDL cannot contain free amino acids! Apo B-100 is a large protein!]
3. It is released into circulation.
4. It then take up apo C and apo E from HDL (High density lipoprotein).
5. Apo C will activate Lipoprotein lipase in cappilary epithelium to break down triacylglycerol in VLDL into fatty acid and glycerol. [It should be capillary endothelium.]
6. Now VLDL decrease in volume increase in density and now convert to IDL (intermediate density lipoprotein).
7. IDL bind to lipoprotein receptor at hepatocyte  via apo E through endocytosis. [IDL are internalized by endocytosis.]
8. In the hepatocyte, triacylglycerol in IDL (undergo) further break down by hepatic lipase.
9. Now the compound is increase in density and rich in cholesterol.
10. It is now LDL (low density lipoprotein).
11. It will (be) released by the hepatocyte.
12. After that LDL (is) either absorb(ed) by the liver or posthepatic tissues to (be) further metabolize(d).

Example 3

1. In the lipoprotein metabolism, it consist the exogenous pathway, endogenous pathway and the reverse metabolism pathway. [F] [There is no such thing as reverse metabolism pathway! There is reverse cholesterol transport.]
2. During the endogenous pathway it is started in the liver.
3. From the very low density lipoprotein (VLDL) which is present inside our body will produce in the liver, 
4. It is function to bring the cholesterol to the tissue cell for storage.
5. When it enter the circulation it will undergo lypolysis and converted into the Intermediate density lipoprotein (IDL). 
6. This IDL is appear in the blood just for a while. [Transient]
7. Next the IDL will undergo the lipolysis and then being the low density lipoprotein (LDL).
8. This LDL will deposit into our tissue.
9. Plus the LDL is very anthrogenic [atherogenic], thus LDL will lead into the formation of the atherosclerotic plaque and lead to other disease.
10. This plaque prone to forming more at the abdominal aorta than the thoracic aorta.
11. This LDL that deposit inside the tissue will be taken up back into the liver via the high density lipoprotein (HDL) during the reverse lipoprotein pathway. [Reverse cholesterol transport]
12. The LDL serve as the bad cholesterol inside our body.
13. {Diagram}

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WRONG answers attempted by students (0 marks)

Example 1

1. Chylomicrons are found in intestinal mucosa from dietary lipid. 
2. During the endogenous pathway, high density lipoprotein (HDL) serves as reservoir for apo-C and apo E. [F] [Chylomicron metabolism is exogenous pathway.]
3. The apo-C and apo-E will bind to chylomicrons.
4. As chylomicrons enters the blood circulatory system, lipoprotein lipase (LPL) will hydrolyse the triglycerides into free fatty acid and glycerol.
5. As the triglycerides are broken down, the size of chylomicrons decreases, becomes smaller but its density increases.
6. The Apo-I in chylomicrons will restore back to high density lipoprotein before reaching liver  while the apo-E will stay with the chylomicrons. [Which apolipoproteins go where?]
7. The remnants of chylomicrons reach liver, and will be metabolized as source of energy, heat energy. [F] [What do chylomicron remnants contain?]

Example 2

1. Endogenous pathway of lipoprotein metabolism begins with the absorption of chylomicrons. [F]
2. The chylomicron binds with Apo B-II. [F] [There is no such thing as Apo B-II.]
3. The chylomicron then travels through the lymphatic system while being metabolised by lipoprotein lipase .
4. After a few stages of digestion, the chylomicron enters the liver.

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WRONG answers mixed with correct answers

Example 1 (2 marks)

1. Endogenous pathway.
2. The lipoprotein is transported as VLDL. [1 mark]
3. Then, it changes into LDL. [1 mark]
4. The LDL form chylomicron. [F]
5. Chylomicron is absorb(ed) by lacteal. [irrelevant]
6. Then it moves into blood. [irrelevant]

Example 2 (4 marks)

1. When dietary lipids and cholesterol enter intestine, they (are) converted to tryglyceride, monoglyceride  and fatty acids by intestinal lipase. [The correct spelling is triglyceride.]
2. They are absorbed into intestinal cells which (are) then converted into tryglyceride by golgi apparatus [Golgi apparatus].
3. Tryglyceride, cholesterol will be bind forming chylomicrons (CM). 
4. Chylomicrons are too big to enter blood vessels so it will enter lacteals which then enter blood vessels.
5. CM are utilised by lipase that (are) present in blood vessels forming smaller lipids to be transported to muscle cells for energy and to liver for storage,
6. CM are then transported to liver.
7. Cholesterol will bind to Apo B to form very low density lipoprotein (VLDL). [1 mark]
8. VLDL will be transported in blood vessels where it  (is) utilised by tissues converting it to Intermediate density lipoprotein (IDL). [1 mark]
9. IDL (is) transported to liver forming Low density lipoprotein (LDL). [1 mark]
10. LDL is then again circulated in blood to be utilised by tissues for energy. [1 mark]

End

Age-Related Macular Degeneration

Abbreviations
AMD
ARMD


INTRODUCTION

Eyesight is partly determined by genetics (inherited) and partly by nutrition and the environment (acquired). When we were born, we had good eyesight as newborns, and as little boys and girls growing up. Our eyes are either like those of our parents, grandparents or great-grandparents. If they had "strong eyes", we too have strong eyes. If they had "weak eyes", we too have weak eyes. However, not all parents with good eyesight give rise to children with good eyesight. Many poor children have good eyesight despite their "poor nutritional intake" and they spend a lot of time playing outside under the bright hot sun, even at noon. 

What then causes eyesight to deteriorate? Our eyesight deteriorates as we age. The macula degenerates as we age, giving rise to age-related macula degeneration (AMD or ARMD).

At age between 40-42, almost all adults have lens and macula changes, that they need bifocals to help them read and get on with life. When you see a person holding the newspaper about 3 feet from his/her face, you automatically know he is 40 and above. A person less than 40 usually does not have to hold the newspaper this far to be able to read it. This is more obvious in males. Females usually do not need glasses to read the newspaper or a book. So it is harder to tell if a woman is past 40.

Can we cure AMD or ARMD? No, at least not yet. Can we slow down the process? Yes, by eating proper nutrition. What should we eat? It depends on whom we are asking, which community we are studying, what our references are and which group of nutritionists are advising us.

MALAYSIA

In the old days, Malayans hardly wore glasses. Big fat men wore glasses to read newspaper. Big fat women wore cat-eye styled eyeglasses, fondly referred to as "spek mata kucing". These were favorite characters depicted in Lat's cartoon pages, Malaysia's top cartoonist.

Many Malaysians today wear eyeglasses (spectacles) or dark sunglasses (shades). Some wear ones with variable tint. Eyeglasses are expensive luxury items and not many who need them can get them at affordable price.

Malaysia is a hot humid country with temperatures ranging from 24 (night) to 31/32 (day). It has indigenous tribes in various parts, in peninsula Malaysia and Borneo. The ones living in the peninsula are grouped as Orang Asli, now re-termed Orang Asal (original dwellers or sons of the soil). They have their own simplistic  lifestyles which are different from how mainstream Malaysians live and dine.

Malaysia has a small Indian population. However, the Malays of the western coastal states of Perlis, Penang, Perak. Selangor, Malacca, and Negeri Sembilan have large widespread Indian populations. The rest of the Malay States have isolated Indian populations at rubber estates and other local farming locales. The Indians believe that brinjals (eggplants) give good eyesight. Brinjals are cooked as part of Indian curries (dalca) or coated with tumeric-salt mixture and then fried. These are eaten with either plain hot white rice or accompany briyani rice (nasi briyani). Nasi briyani has become a national favourite and is now served at most weddings and official dinners. Sometimes an oily rice (nasi minyak) is served instead of nasi briyani.

Case:

An 11-year old schoolgirl experienced problems viewing text and numerals written on the blackboard in class at school. She was short-sighted. She started wearing eyeglasses at age 12 and sat at the rear of her classroom. Throughout her primary, secondary, and tertiary studies, she needed countless changes of eyeglasses as her eyesight continued to deteriorate; at least annual change of eyeglasses. She wore contact lenses at 21-22 as a university student. 

At 41, she was diagnosed of gestational diabetes mellitus (GDM) at her last pregnancy (para6 gravida6; P6G6). At 42, she experienced changes in her lens; she became bifocal and needed glasses for far-sight to be able to read road signs and signboards properly. At 50 she had abnormalities involving the retina.

Fundoscopy - Ophthalmoscopic exam of the human retina.

At 59, she wears eyeglasses with plastic lens costing her RM790 by mail order. What is wrong with her eyesight? She has macular degeneration + astigmatism. 

Blood chemistry at 59
(After 13-hour overnight fasting AND after 20 days of 13-hr Ramadan fasting)

Renal profile: normal
Liver function test: normal
Fasting lipid profile:
  HDL-cholesterol (HDLC): 0.90 mmol/L (W 0.78-2.20; Direct inhibition method)
  LDL-cholesterol (LDLC): 3.57 mmol/L (W 2.33-4.70; calculated Friedewald formula)
  Total cholesterol (TC): 5.02 mmol/L (normal 3.6-6.3; Cholesterol oxidase method)
  Triglycerides (TG): 1.21 mmol/L (W 0.46-1.60; GPO-PAP method)
Fasting blood sugar (FBS)/Fasting blood glucose (FBG): 5.5 mmol/L 

BP: 140/90
BMI: >30

AUSTRALIA

Five hours flight down-under from Malaysia is Australia. Australia is noted for clean air, clean environment, good food, good nutrition and good health.

The indigenous people of Australia are the Aborigines or "Abo".  They are evolutionary linked to the indigenous people of the archipelago just above Australia and south of the Asian mainland. It is generally believed that Australia was part of a bigger land mass south of the Asian mainland, and indigenous people walked the Earth on one enormous land mass.

The hunting skills of the indigenous people point to their sharp vision. Most hunt with a blowpipe and poison darts.They are able to locate small objects like watering holes in boulders and what lies in the immediate surrounding. A tour of the Australian outback gives a good idea of their skills that have kept them alive for years immemorial.

The Australian Aborigines are noted to have super sight, but for a limited time of their life span. Their newborns are born with super sight and the aboriginal children continue to have super sight in adulthood till approximately age 40, where their sight begins to deteriorate from habitual practice and modern ill-health. They did not suffer from macular degeneration till age 40.

Today, Australia is a melting pot of many cultures since mass immigration began in the 1800s. Its cuisine is varied and reflects its various immigrant communites. The Australian-Egyptian oily rice dish uses large sliced Bombay onions fried in butter. The rice is then mixed in and steamed till done. The aroma is that of buttery fried onion. This type of rice dish is mostly served at festivities - eg Aidilfitri (Eid-ul-Fitr) at Perth Mosque.

Do immigrant communities have poorer vision than the Aborigines? Yes, but before age 40.

THE AMAZON

The Amazon River basin is hot and humid with thick equatorial jungles and thick undergrowth. It houses several tribes, some isolated and some who have mixed with more civilized communities. They are highly skilled hunters on land and on the river.

AFRICA

African tribes are skilled hunters in the arid and dusty safari setting, where trees are minimal and shrubs abound. Mirages are common. Hunters must be able to tell where the animals are hiding among the trees and shrubs, or where they are grazing ... near watering holes or creeks.


External links:

Pinterest: normal vs macula degenration
https://www.pinterest.com/pin/289778557269264673/
https://www.pinterest.com/pin/130745195412073753/?lp=true

Adam
http://pennstatehershey.adam.com/content.aspx?productId=42&pid=42&gid=000243

Wikipedia: Macular degeneration and Hypertensive retinopathy
https://en.wikipedia.org/wiki/Macular_degeneration
https://en.wikipedia.org/wiki/Hypertensive_retinopathy

Diabetic retinopathy
https://decisionmakerplus.net/case-report-post/diabetic-retinopathy-without-macular-edema-2/

ABC: Australian Aborigines with super sight
http://www.abc.net.au/news/2015-04-08/prince-harry-may-struggle-to-keep-up-with-aboriginal-super-sight/6378066

OPS: Online education
https://www.opsweb.org/page/onlineedu4CEC?

Stanford Medicine: Clinical pictures of retina
https://stanfordmedicine25.stanford.edu/the25/fundoscopic.html

Visuals
https://medivisuals1.com/ophthalmoscopic-view-of-normal-retina-10512303x.aspx

YouTube videos
https://youtu.be/QukG5RRqjZo
https://youtu.be/-iuumsGWo6k
https://youtu.be/YP1nbM3x-uU
https://youtu.be/8cX3ifSar9s
https://youtu.be/3RyOItWYJQM
https://youtu.be/8FWIfcmlWn4

Listeria Listeriosis

Order: Bacillales
Class: Bacilli
Genus: Listeria

Species: There are 6 species of Listeria.
L. monocytogenes, L. ivanovii, L. innocua, L. welshimeri, L. seeligeri, and L. grayi
Only L. monocytogenes infects humans and makes us ill.

Serotypes: There are 13 serotypes of L. monocytogenes that can cause disease in humans. More than 90 percent of human isolates belong to only three serotypes: 1/2a, 1/2b, and 4b.

Listeriosis
- is the disease caused by Listeria monocytogenes (L. monocytogenes)

Manifestations of listeriosis
- febrile gastroenteritis
- septicemia
- meningitis
- corneal ulcer
- pneumonia
- miscarriage
- spontaneous abortion
- premature delivery
- stillbirth

Listeria monocytogenes
- named after Joseph Lister
- Gram positive bacterium (rod shape)
- motile (flagellate with actin rockets/comet tails) - tumbling motility (tergolek-golek)
- flagellate & aflagellate forms; grows flagella at 30C and below; no flagella at 37C (body temperature)
- peritrichous flagella at RT (20-25C)
- nonspore-forming (doesn't form spores) - no spores to disseminate the bacteria
- found in human gut or gastrointestinal (GI) system - up to 10% is L. monocytogenes
- virulent food-borne pathogen - can infect humans and cause 20-30% death
- facultatively anaerobic - can survive with & without oxygen (ie inside cells)

Transmission
- vertical transmission: mother to child when giving birth (childbirth) - transvaginal - fetomaternal listeriosis
- newborns can get the disease from their mothers if their mothers ate contaminated food
- expectant mothers to avoid soft cheeses which may be contaminated with L. monocytogenes

Food contamination
- many sources - raw food, fruits and vegetables, fruit salads, salads, coleslaw, unpasteurized milk & food
- sheep manure can contaminate cabbage - cabbage is made into coleslaw (raw cabbage) - contaminated coleslaw may cause consumers to become ill (foodborne listeriosis)

Development of listeriosis
- from days to weeks

Pathogenicity
-  causes meningitis in newborns (rengsa selaput otak bayi) - 3rd most common cause of meningitis in newborns

Recent outbreaks
- South Africa - ready-to-eat meat (cold meats)
- Australia - rock melons or cantaloupes

Industries affected
- food industry
- import & export
- tourism
- business travels

Detection in the clinical diagnostic labs
- old way - hemolysin test
- modern way - DNA methods

Treatment
- antibiotics


External links
Encyclopedia of Life (EOL)
http://eol.org/pages/974245/details
https://www.sowetanlive.co.za/news/south-africa/2018-03-22-who-no-need-to-ban-sa-meats/
https://mg.co.za/article/2018-03-21-three-major-mistakes-tiger-brands-made-in-response-to-the-listeriosis-crisis
http://punchng.com/who-warns-nigeria-15-other-african-countries-of-listeriosis-outbreak/
https://www.webmd.com/food-recipes/food-poisoning/tc/listeriosis-topic-overview
https://en.wikipedia.org/wiki/Listeriosis

Rapidly ascending numbness in the legs

A 78-year old Malay widow was a globe-trotter. However, she suddenly experienced numbness in both her legs. Within 10 days, her numbness had spread upward to both thighs and waist. She was depressed.


What could be the cause of her numbness?

How can she be cared for at home?

What must be monitored when caring for her at home?

How can her condition be investigated?

What test(s) can be done?

Is there treatment for her condition?

Can her condition improve?

Will her condition worsen?

What advice will you give her caregivers?

Vitamin E
Vitamin E deficiency leads to muscle weakness and sight problems. Vitamin E oil (softgel capsules) may help to reduce the patient's leg numbness. Vitamin E is neuro-regenerative and helps nerves to grow or create new networks around lesions or problematic areas. How soon, what dose, how extensive, how effective, all these questions will depend on existing research findings and future research on vitamin E on nerve regeneration.


External links
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2522257/
http://pn.bmj.com/content/

Pokok Kanser (anti-cancer plant)

I visited a friend's house at Sri Gemilang in Kota Bharu, Kelantan.

She had this plant which had thick waxy leaves, dark green fruits in clusters, and bright yellow flowers which smelled of a cross between nangka (jackfruit), magnolia (bunga magnolia or bunga telur) and bunga kenanga.

She said the leaves have anticancer properties. She didn't know its name. She called it Pokok Kanser (anti-cancer plant).

Thick waxy leaves and fragrant, bright yellow flower or hirva chafa

Thick waxy leaves and green fruits in cluster. The fruits will ripen and turn yellow, just like bananas do.

Scientific Name: Artabotrys hexapetalus 
Family: Annonaceae
Common Name: Green champa, Hirava chafa
In Indian, it is called the Hirva chafa flower.
Description: A large woody rambler. Flowers are greenish yellow
Synonym: A. odoratissimus

Varieties:
Artabotrys odorattisimus (Hirwa chafa or Hirva chafa)
Artabotrys uncinatus
Artabotrys hexapetalus
Cananga odorata or Ylang Ylang (sweet myrrh)

Uses

1. Anti-cancer
2. Depression
3. High blood pressure
4. Aromatherapy

External links
http://www.floraofbangladesh.com/2016/11/kathali-chapa-artabotrys-hexapetalus.html
Green champa | Gardentia (gardentia.net)
http://www.chhajedgarden.com/artabotrys-uncinatus-pack-of-2.html
https://shop.lebermuth.com/products/oil-ylang-ylang-myrrh-bbw
http://www.lgbotanicals.com/Ylang-Ylang-Complete-Organic-Essential-Oil_p_292.html
http://www.ehorticulture.com/tree-plants-seeds/ornamental-plants/artabotrys-hexapetalus-detail.html
http://www.flickriver.com/photos/tags/artabotrysodoratissimus/interesting/

Amylase test and Acute pancreatitis

Description

Amylases are enzymes that catalyze the hydrolysis of amylopectin, amylose, glycogen, and their hydrolyzed products into simple and easily digestible sugars. Amylase is an enzyme produced in the pancreas and by the salivary glands that converts starches, glycogens, and related polysaccharides into simple and easily digested sugar. It is also present in molds, bacteria, yeasts, and plants.

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Amylase isoenzymes
Alpha amylase is of salivary origin (S-type amylase) or pancreatic origin (P-type amylase).

1. Salivary origin (S-type amylase)
2. Pancreatic origin (P-type amylase)

Salivary amylase is synthesized by parotid, sweat, and lactating mammary glands.

Pancreatic amylase is secreted by acinar cells of the pancreas and is tissue specific and more temperature labile than salivary amylase.

Separation of amylase enzyme (a protein) by slab gel electrophoresis
On agarose gel, the mobility of the less anionic isoenzyme corresponds to pancreatic amylase, while the more anionic band is salivary amylase.

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Macroamylasemia
Macroamylasemia is a condition of persistently elevated serum amylase activity with no apparent pancreatic disorder due to the formation of a large amylase-globulin complex, which is not excreted.

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Test overview
An amylase test measures the amount of this enzyme in a sample of blood taken from a vein or in a sample of urine.

1. Blood/serum amylase
2. Urine amylase

Amylase levels
Normally, only low levels of amylase are found in the blood or urine. However, if the pancreas or salivary glands become damaged or blocked, more amylase is usually released into the blood and urine. In the blood, amylase levels rise for only a short time. In the urine, amylase may remain high for several days.

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Symptoms
Almost everyone with acute pancreatitis has severe abdominal pain in the upper abdomen. The pain penetrates to the back in about 50% of people.

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Causes & pain

1. When acute pancreatitis is caused by gallstones, the pain usually starts suddenly and reaches its maximum intensity in minutes. 
2. When pancreatitis is caused by alcohol, pain typically develops over a few days. 

Whatever the cause, the pain then remains steady and severe, has a penetrating quality, and may persist for days.

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Pain & relief
Coughing, vigorous movement, and deep breathing may worsen the pain. Sitting upright and leaning forward may provide some relief. Most people feel nauseated and have to vomit, sometimes to the point of dry heaves (retching without producing any vomit). Often, even large doses of an injected opioid analgesic do not relieve pain completely.

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Breathing problems
Some people, especially those who develop acute pancreatitis because of heavy alcohol use, may never develop any symptoms other than moderate to severe pain. Other people feel terrible. They look sick and are sweaty and have a fast pulse (100 to 140 beats a minute) and shallow, rapid breathing. Rapid breathing may also occur if people have inflammation of the lungs, areas of collapsed lung tissue (atelectasis), or accumulation of fluid in the chest cavity (pleural effusion). These conditions may decrease the amount of lung tissue available to transfer oxygen from the air to the blood and can lower the oxygen levels in the blood.

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Body temperature
At first, body temperature may be normal, but it may increase in a few hours to between 100° F and 101° F (37.7° C and 38.3° C).

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Blood pressure
Blood pressure is usually low and tends to fall when the person stands, causing lightheadedness or transient loss of consciousness (TLOC) or syncope.

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Yellow sclerae
Occasionally, the whites of the eyes (sclera) become yellowish.

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Complications of acute pancreatitis

The main complications of acute pancreatitis are

1. Low blood pressure and shock
2. Damage to other organs
3. Infection of the pancreas
4. Pancreatic pseudocyst

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Pancreatic damage
Damage to the pancreas may permit activated enzymes and toxins such as cytokines to enter the bloodstream and cause low blood pressure and damage to other organs, such as the lungs and kidneys. Some people who have acute pancreatitis develop failure of other organs including the kidneys, lungs, or heart, and this failure can lead to death.

The part of the pancreas that produces hormones, especially insulin, tends not to be affected by acute pancreatitis.

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Swollen upper abdomen
In acute pancreatitis, a person may develop some swelling in the upper abdomen. This swelling may occur because the intestinal contents have stopped moving, causing the intestines to swell (a condition called ileus).

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Acute pancreatitis
In severe acute pancreatitis, parts of the pancreas may die (called necrotizing pancreatitis), and body fluid may escape into the abdominal cavity, which decreases blood volume and results in a large drop in blood pressure, possibly causing shock and organ failure. Severe acute pancreatitis can be life threatening.

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Inflammed pancreas (due to infection)
Infection of an inflamed pancreas is a risk, particularly after the first week of illness. Sometimes, a doctor suspects an infection when a person's condition worsens and a fever develops, especially if this happens after the person's first symptoms started to subside.

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Pancreatic pseudocyst
A pancreatic pseudocyst is a collection of pancreatic enzymes, fluid, and tissue debris that sometimes forms in and around the pancreas. The pseudocyst goes away spontaneously in some people. In other people, the pseudocyst does not go away and can become infected.

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Diagnosis
Blood tests
Imaging tests

Characteristic abdominal pain leads a doctor to suspect acute pancreatitis, especially in a person who has gallbladder disease or who drinks a lot of alcohol. During the examination, a doctor often notes that the abdomen is tender and the abdominal wall muscles may be rigid. When listening to the abdomen with a stethoscope, a doctor may hear few or no bowel (intestinal) sounds.

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Blood tests
No single blood test proves the diagnosis of acute pancreatitis, but certain tests suggest it. Blood levels of two enzymes produced by the pancreas—amylase and lipase—usually increase on the first day of the illness but return to normal in 3 to 7 days. If the person has had other flare-ups (bouts or attacks) of pancreatitis, however, the levels of these enzymes may not increase significantly, because so much of the pancreas may have been destroyed that few cells are left to release the enzymes.

The white blood cell count and blood urea nitrogen level (marker of kidney function) are usually increased.

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Imaging tests
X-rays of the abdomen may show dilated loops of intestine or, rarely, one or more gallstones. Chest x-rays may reveal areas of collapsed lung tissue or an accumulation of fluid in the chest cavity.

An ultrasound of the abdomen may show gallstones in the gallbladder or sometimes in the common bile duct and also may detect swelling of the pancreas.

A computed tomography (CT) scan is particularly useful in detecting inflammation of the pancreas and is used in people with severe acute pancreatitis. Because the images are so clear, a CT scan helps a doctor make a precise diagnosis and identify complications of pancreatitis.

Magnetic resonance cholangiopancreatography (MRCP), a special magnetic resonance imaging (MRI) test, may also be done to show the pancreatic- duct and bile duct and to determine if there is any dilation, blockage, or narrowing of the ducts.

Endoscopic retrograde cholangiopancreatography allows doctors to view the bile duct and pancreatic duct. During this test, doctors are able to remove from the bile duct gallstones that are causing a blockage.

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Other tests
If doctors suspect that there is an infection, they may withdraw a sample of infected material from the pancreas by inserting a needle through the skin into the fluid collection.

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Prognosis
In acute pancreatitis, a CT scan helps determine the outlook or prognosis. If the scan indicates that the pancreas is only mildly swollen, the prognosis is excellent. If the scan shows large areas of destroyed pancreas, the prognosis is usually poor.

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Scoring (arbitrary)
A number of scoring systems help doctors predict the severity of acute pancreatitis, which can help them better manage the person. These scoring systems may include information such as age, medical history, physical examination findings, laboratory tests, and CT scan results.

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Death
When acute pancreatitis is mild, the death rate is about 5% or less. However, in pancreatitis with severe damage, or when the inflammation is not confined to the pancreas, the death rate can be much higher. Death during the first several days of acute pancreatitis is usually caused by failure of the heart, lungs, or kidneys. Death after the first week is usually caused by pancreatic infection or by a pseudocyst that bleeds or ruptures.

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Treatment

1. Fasting
2. Fluids by vein
3. Pain relief
4. Measures to support nutrition
5. Sometimes endoscopy or surgery

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Treatment
Treatment of mild acute pancreatitis usually involves short-term hospitalization where fluids are given by vein (intravenously / i.v.), analgesics are given for pain relief, and the person fasts to try to rest the pancreas. A low-fat, soft diet is usually started soon after admission if there is no nausea, vomiting, or severe pain.

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Intravenous fluids
People with moderate to severe acute pancreatitis need to be hospitalized for a longer period of time and are given intravenous fluids. They must initially avoid food and liquids, because eating and drinking stimulate the pancreas. Symptoms such as pain and nausea are controlled with drugs given intravenously. Doctors may give antibiotics if these people show any signs of infection.

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People with severe acute pancreatitis are admitted to an intensive care unit (ICU), where vital signs (pulse, blood pressure, and rate of breathing) and urine production can be monitored continuously.

Blood samples are repeatedly drawn to monitor various components of the blood, including the following:

1. Hematocrit (Hct), 
2. Blood sugar (glucose) levels, 
3. Electrolyte levels, 
4. White blood cell (WBC) count, and 
5. Blood urea nitrogen (BUN) levels or Urea levels.*

*Urea analysis is performed nowadays, where urea nitrogen is measured and multiplied by 2 and reported as urea levels.

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Nasogastric tube

A tube may be inserted through the nose and into the stomach (nasogastric tube) to remove fluid and air, particularly if nausea and vomiting persist and ileus is present.

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Parenteral nutrition
People with moderate to severe acute pancreatitis are often given nutrition via a thin plastic tube that is inserted through the nose and down through the stomach into the small intestine (tube feeding). Less often, people are given intravenous feeding.

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Other
For people with a drop in blood pressure or who are in shock, blood volume is carefully maintained with intravenous fluids and drugs and heart function is closely monitored. Some people need supplemental oxygen, and the most seriously ill require a ventilator (a machine that helps air get in and out of the lungs).

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Pancreatitis due to gallstones
When acute pancreatitis results from gallstones, treatment depends on the severity. Although more than 80% of people with gallstone pancreatitis pass the stone spontaneously, ERCP with stone removal is usually needed for people who do not improve because they have a stone they cannot pass. At some point, the gallbladder is usually removed but if the pancreatitis is severe, removal of the gallbladder can usually be delayed until symptoms subside.

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Pseudocysts & drainage
Pseudocysts that have rapidly grown larger or are causing pain or other symptoms are usually drained. Depending on its location and other factors, a pseudocyst can be drained by doing a surgical procedure, or by placing a drainage tube (catheter) into the pseudocyst. The catheter can be placed using an endoscope or by inserting the catheter directly through the skin into the pseudocyst. The catheter allows the pseudocyst to drain for several weeks.

An infection is treated with antibiotics, and may require removal of infected and dead tissue endoscopically or surgically.

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Indications/Applications
Most elevations in serum amylase are due to increased rates of amylase entry into the blood stream, decreased rates of clearance or both. The test is primarily used, in conjunction with a lipase test, to help diagnose and monitor acute pancreatitis and other pancreatic disorders. Serum amylase increases in 6-48 hrs of onset of acute pancreatitis but not in proportion to the severity of the disease and activity returns to normal in 3-5 days. Urine amylase increases in proportion to serum amylase and remains elevated for several days after serum amylase has been normalized. The ratio of amylase urinary clearance to creatinine clearance can be used in the diagnosis of acute and relapsing pancreatitis.

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Other uses of serum amylase test
Serum amylase levels can also be elevated in pancreatic cancers, although a bit too late to be diagnostically useful; however, the results can assist in monitoring treatment of pancreatic cancers. Other conditions in which determination of serum amylase is useful is to determine the effects of the removal of gallstones, and swelling and inflammation of the salivary/parotid glands.

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Indications for testing are as follows:

• Severe abdominal pain
• Fever
• Loss of appetite (LOA)
• Nausea

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Causes
The most common causes (more than 70% of cases) of acute pancreatitis are

1. Gallstones
2. Heavy alcohol intake
3. Other causes

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Gallstones
Gallstones cause about 40% of cases of acute pancreatitis. Gallstones are collections of solid material in the gallbladder. These stones sometimes pass into and block the duct that the gallbladder shares with the pancreas (called the common bile duct).

Normally, the pancreas secretes pancreatic fluid through the pancreatic duct into the first part of the small intestine (duodenum). This pancreatic fluid contains digestive enzymes that help digest food. If a gallstone becomes stuck in the sphincter of Oddi (the opening where the pancreatic duct empties into the duodenum), pancreatic fluid stops flowing. Usually, the blockage is temporary and causes limited damage, which is soon repaired. But if the blockage remains, the enzymes collect in the pancreas and begin to digest the cells of the pancreas, causing severe inflammation.

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Alcohol
Alcohol use causes about 30% of cases of acute pancreatitis and usually occurs only after heavy alcohol use. The risk of developing pancreatitis increases with increasing amounts of alcohol (4 to 7 drinks per day in men and 3 or more drinks per day in women). How alcohol causes pancreatitis is not fully understood. One theory is that alcohol is converted into toxic chemicals in the pancreas that cause damage. Another theory is that alcohol may cause the small ductules in the pancreas that drain into the pancreatic duct to clog, eventually causing acute pancreatitis.

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Other causes
For some people, acute pancreatitis is hereditary. Gene mutations that predispose people to developing acute pancreatitis have been identified. People who have cystic fibrosis or carry the cystic fibrosis genes have an increased risk of developing acute as well as chronic pancreatitis.

Many drugs can irritate the pancreas. Usually, the inflammation resolves when the drugs are stopped.

Viruses can cause pancreatitis, which is usually short-lived.

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SOME CAUSES OF ACUTE PANCREATITIS

1. Gallstones
2. Heavy alcohol use
3. Drugs such as angiotensin-converting enzyme (ACE) inhibitors, azathioprine, furosemide, 6-mercaptopurine, pentamidine, sulfa drugs, and valproate
4. Estrogen use in women with high levels of lipids in the blood
5. High levels of calcium in the blood (which may be caused by hyperparathyroidism)
6. Viruses such as mumps, coxsackie B virus, and cytomegalovirus
7. High levels of triglycerides in the blood (hypertriglyceridemia)
8. Damage to the pancreas caused by surgery or endoscopy (such as endoscopic retrograde cholangiopancreatography [ERCP])
9. Damage to the pancreas caused by blunt or penetrating injuries
10. Cancer of the pancreas, or other blockages of the pancreatic duct
11. Hereditary pancreatitis, including a small percentage of people with cystic fibrosis or cystic fibrosis genes
12. Cigarette smoking
13. Kidney transplantation
14. Pregnancy (rare)
15. Tropical pancreatitis

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Biochemical markers for acute pancreatitis

Serum amylase & serum lipase tests
Serum amylase and lipase are common tests obtained as biochemical markers for acute pancreatitis.

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Blood collection and test panels

The 2 tests for amylase are serum and urine.
For both tests, patient should not drink alcohol for 24 hours before the test.

For the blood test, patients should not eat or drink anything except water for 2 hours before the test.

For the urine test, patients should drink enough fluids during the 24-hour test to avoid dehydration. In this test, patients should check with their physician about any medications being taken. Timed urine specimens can be obtained for urinary amylase and normalized to creatinine content.

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How to Prepare for Amylase Test

To prepare for an amylase test:

1. Do not drink alcohol for 24 hours before the test.
2. For a blood test for amylase, do not eat or drink anything except water for at least 2 hours before having the test.
3. For a 24-hour urine test for amylase, be sure to drink enough fluids during the test to prevent dehydration.

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Methods
Blood is collected into a vacuum tube via venipuncture (ie blood is obtained from a vein in the arm).

For urine, a patient urinates into a small container and then transfers the sample to a lab-provided larger container with a small amount of preservative.

Plasma samples that have been anticoagulated with citrate or oxalate should be avoided because amylase is a calcium-containing enzyme and false low levels can be obtained with such specimens.

Notes regarding these methods are as follows:

Keep container refrigerated.
Do not touch inside of container or drop any foreign matter into it.

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Test panels

Related tests are as follows:

1. Lipase test
2. Urinalysis
3. Urine creatinine/clearance
4. Isoamylase fractionation

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LABORATORY TEST & FINDINGS

Set up for manual serum amylase test

Reference range
Each lab has its own reference ranges for the tests that it offers.

The reference range for amylase is as follows:

Serum test: Normal is 40-140 U/L
Urine Test: Normal is 24-400 U/L

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Interpretation of serum amylase levels

Conditions associated with high amylase levels are as follows:

1. Peptic ulcers
2. Intestinal obstruction
3. Pancreatic duct obstruction
4. Cancer
5. Gallbladder attacks
6. Mesenteric thrombosis
7. Postoperative abdominal surgery
8. Mumps
9. Macroamylasemia
10. Tubal pregnancy

Conditions associated with low amylase levels are as follows:

1. Liver damage
2. Cystic fibrosis
3. Pancreatic cancer
4. Toxemia of pregnancy

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Pancreatic enzymes and products

Early in the course of acute pancreatitis, there is a breakdown in the synthesis-secretion coupling of pancreatic digestive enzymes; synthesis continues while there is a blockade of secretion. As a result, digestive enzymes leak out of acinar cells through the basolateral membrane to the interstitial space and then enter the systemic circulation.

Serum amylase
Serum amylase rises within 6 to 12 hours of the onset of acute pancreatitis. Amylase has a short half-life of approximately 10 hours and in uncomplicated attacks returns to normal within three to five days. Serum amylase elevation of greater than three times the upper limit of normal has a sensitivity for the diagnosis of acute pancreatitis of 67% to 83% and a specificity of 85% to 98%.

However, elevations in serum amylase to more than three times the upper limit of normal may not be seen in approximately 20% of patients with alcoholic pancreatitis due to the inability of the parenchyma to produce amylase, and in 50% of patients with hypertriglyceridaemia-associated pancreatitis as triglycerides interfere with the amylase assay. Given the short half-life of amylase, the diagnosis of acute pancreatitis may be missed in patients who present >24 hours after the onset of pancreatitis. In addition, elevations in serum amylase are not specific for acute pancreatitis and may be seen in other conditions.

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Sensitivity & specificity of amylase & lipase tests for pancreatitis
The sensitivity and specificity of amylase and lipase for pancreatitis depend upon the threshold for an abnormal result. Higher thresholds are associated with better specificity but lower sensitivity. Several studies suggest that lipase may be more specific than amylase in the diagnosis of acute pancreatitis. A lipase level of three times the upper limit of normal is approximately 98% specific for acute pancreatitis.

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Acknowledgement
Text and content are adapted from Up-To-Date and many test methods by various vendors, and made easy for small group discussion (SGD) for Phase I teaching-learning sessions.

Itch and pain in the female GUS & ReproS

The female genitourinary system (GUS) and reproductive system (ReproS) are close together and  delicate. They are a woman's best friend. The female genitalia must be properly washed daily, each time after defecation or urination. Soaps and body wash gels and liquids used for personal hygiene matters for the female, not so much for males.

I'm bringing up this matter because this is a common problem in females, and many females end up coming to hospital or clinic for pain in the genitalia and/ ReproS. 

Young women and old women also get infections of the female genitalia. Mothers often have hematuria (blood in urine, bloody urine) and pain urinating following maternal delivery. Non pregnant women and menopausal women also get infections, but less frequent than mothers in their reproductive age.

Infections of the female genitalia can mean a lot of things. It can be just urinary tract infection (UTI). It can be just extreme itch due to Chlamydia trachomatis infection. It can be both UTI and Chlamydia. It can be other things. A good physical examination to locate the itch, pain and examination of the female genitalia becomes necessary. Itch with yellowish discharge indicate pus, coming from an infection. 

Sometimes doctors do not convey the condition clearly to their female patients, leaving the patients lost as to what conditions they actually have. This is bad enough as women tend to worry a lot when something goes wrong in the most private part.

Here is a scenario to let you see the scope a how a female patient got very worried. Text is edited.

SCENARIO

A 67-year old unmarried female Malay lady lives alone after retirement at 55. She had pain on urination and was admitted to hospital. She was diagnosed to have UTI and prescribed a course of antibiotics. Her condition did not heal after a week and she was again prescribed another course of antibiotics for a week. She was discharged home. 

At home, she was still sensing pain upon urination once in a while. She contacted some friends for help. Her friends tried to help and asked her questions too.

1. She wanted to know if she needed a third course of antibiotics to rid her pain. Her friends replied no, and to seek traditional alternatives.
2. She wanted to know if her blood test results was a sign of stone in the bladder. Her friends asked if the doctors had performed an ultrasound scan of the kidneys and bladder when they did her urine test. She replied no.
3. Her friends told her that renal stones hardly form in the urinary bladder unless she was a "teh tarik" person. They told her that if she was a teh tarik person, then she would have had renal stones by age mid-20s. She replied she did not like tea latte since young. Her friends said they did not think she had renal stones since she was not a teh tarik fan. She had to be a better consumer of teh tarik than the teh tarik man in order to get renal stones.
4. She asked if it was just infection? Her friends believed so it was an occasional infection.
5. She said her doctor first said it was UTI and she was given Zinnat.
6. She said she took 2 courses of antibiotics but her condition did not resolve as she had expected. So she was worried. Her friends tried to calm her down and said her condition would resolve, and was just taking a bit longer.
7. She wanted to know if the lab test results meant a dangerous condition. She was really worried and wanted some clear answers.
8. Her friends told her that even if she kept her personal hygiene super clean, she can still catch an infection. She wanted to know how and why? Why in the world would over-washing and being super clean give infection?
9. She wanted to know if her infection was the side effect of antibiotics, .... possibly a Candida?
10. Her friends told her if she had Candida, she would not and could not remain still as the itch is do severe and dreadful. She said she did not feel any itch, just the pain when urinating.
11. Her friends told her Candida was unlikely in elderly ladies her age. It was just one of those infections.
12. She wanted to know if she had to take MORE ANTIBIOTICS!
13. Her friends tried to calm her down and told her to treat her condition conservatively, ie, to drink warm water regularly, every hour and before bed.
14. She wanted to know if increasing water intake will resolve her condition. Will her infection clear up?
15. Her friends added, yes, conservative treatment is alright, ie, drink water, get some rest, eat boiled food, no spicy food, until her condition improves and clears up.
16. Her friends asked if her pain was increasing or otherwise. 
17. She wanted to know if she was ok, and not worry about her condition.
18. Her friends told her worrying would only add to her existing problem (ie make it worse).
19. She said sometimes there was no pain and at times, there was excruciating pain upon urinating.
20. Her friends told her not to worry too much. She said she was a worrier!
21. According to the lab test results, there was blood in her urine. Her friends explained why.
22. Her friends asked if her urine was cloudy (murky), clear or sandy? She replied it was clear.
23. Her friends responded she had no stones.
24. She furnished her lab test results:  pH 5.5, protein, glucose, ketone nil.
25. Her friends explained she did not drink sufficient water and that she was probably dehydrated, her urine was probably concentrated, with a highly acidic pH (lower limit of normal range). If she had eaten meat (chicken or beef), that too would make her urine highly acidic. Urine pH 5.5 is ok but pH 6.0 is better.
26. She furnished additional lab test results: Epithelial occasional, crystals and casts ... nil. Her friends explained why.
27. She asked if the amount of blood in the test results was not a lot. Her friends replied no.
28. She furnished additional lab test results: WBC up to 100 ... a lot! She was intimidated by the "big numbers".
29. She furnished yet additional lab test results: Leukocyte 3+. Her friends explain why, ie WBCs are raised in infections. They wanted to know if her doctors have found out what bacteria had invaded her.
30. She thanked her friends for alleviating much of her fears about her condition as it was uncomfortable. She wanted to know if she needed to next see a urologist or a gynae.
31. She said when she was admitted, her urine culture did not show which bacteria was significant.
32. She said her first urine test had no RBCs and had no blood in urine.
33. Her friends informed her of likely bacteria as causative agents of her painful episodes upon urination.
34. It has been a week after her discharge from hospital. She lived alone and that caused her a lot of worry.

In the end, her friends managed to counsel her and she was happy that her condition could be easily taken care of. She seemed much happier after getting all the answers she needed. Her doctors should have taken additional time to explain to her, her lab test results and the progress of her condition. It saves the patient a lot of useless worrying when they can be advised on the next course of action to take at home and therefore be in a position for self-help. They in turn can help other friends who face the same condition.

External links
https://en.wikipedia.org/wiki/Chlamydia_trachomatis
https://www.emedicinehealth.com/candidiasis_yeast_infection/article_em.htm