Saturday, 6 January 2018

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.


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.

Friday, 29 December 2017

Chest pain due to emotional distress

Heart problems can arise from many sources and in many forms. With today's hectic life and where the market forces and financial means govern a major part of life, we now see a trend, where young and middle-aged men are falling prey to heart disease.

I have stressed on finance and heart disease. Market crash, burden as guarantors, money swindles, white collar crimes, etc have put many unsuspecting men, as victims of heart disease.

Young people, especially men, need and want to portray a healthy and wealthy clean life in front of an already stressful life. This pressure to perform and conform to societal needs, have made many men predators and other men, victims of con men.

The problem is real and men are falling prey to heart disease. Some have died and many will die. Heart disease will kill more and more younger men who deal with money.

What is the problem? What is the root cause? It is complicated.

Can we stop heart disease? No, but we can try a few things to slow it and prevent it from ever happening.


A 45-year old Malay male banker had difficulty breathing and was brought to A&E at a government hospital near his workplace. He was admitted to CCU where he recovered within 3 days.

He was moved to the open ward where family members could easily visit him during visiting hours. When he was conscious, he explained his "bad luck" to his siblings.

He was prescribed drugs to expand his blood vessels. He felt dizzy when he took the drugs.


1. What was the cause of his heart disease?

He had signed as a guarantor for a "friend" who lived approximately 350 km south. The "friend" disappeared with a large sum of Ringgit. His constant worries got the best of him and he landed in hospital with a heart attack.

2. Can his condition worsen?

Yes, it usually worsens. He has had a prior angiogram performed 12 years prior. He is thus at high risk for heart disease.

3. What advice can you give such a patient?

  1. Don't sign on as a guarantor for anyone.
  2. Don't trust anyone with your $$$.
  3. The best person you trust, will in the end, be the greatest cheat and cheat you!!
  4. Always advise a person who seeks a guarantor, that in this life, "there is no such thing as a human guarantor". 
  5. Life is never guaranteed. Life is on borrowed time. It ends when it ends. The exact end is unknown.
  6. Trust just yourself. Trust only yourself.
  7. Trust your spouse if she can be trusted. Otherwise don't.
  8. Don't deal with money more than what you are willing to lose.
  9. Never trust a friend. Treat friends as suspicious and bad hats unless proven otherwise.
  10. Give him your piece of mind and give him 1001 reasons for not being a guarantor. A human cannot guarantee another person's life, wealth or health. You can only guarantee a burial place.
  11. Play safe, live safe, and hope heart attacks will not come near.
  12. Guarantors have to live a sad life with likely heart attacks.
  13. Guarantors are at high risk of heart attacks.
  14. Don't become guarantors unlike you wish a heart attack to befall you!

4. What do you think this patient will do after he is discharged from hospital?

Well, he can go looking for the "friend" who cheated him, or he can hire a private investigator to locate the "friend" and charge him in court. That way money matters can be settled quickly and the "friend: can be tried for cheating etc. Then the heart attacks should resolve and not return. Easier said than done.

5. Are men really brave enough to turn a friend away when he is seeking financial help, as in this case, a guarantor?

Grown-up married men should never ever have to become guarantors for anyone and for anything. Forget trying to help a friend. Forget trying to look good. Forget trying to display generosity. It does not pay to be a kind friend of a con man.

6. What sort of psychological war goes on inside men, that men believe they can become successful guarantors and minus the worries of being one?

It is just silly. Being silly adds to endless worries, and worries add up to give a heart attack ... all in good time.

7. Are men honest about their health and wealth status?

Some men are honest. Many are not. Banks have guarantors to save their loans, to ensure they get back what they loaned out, plus interest, of course. Repayment of banks loans is the most difficult for banks to do without brute force or court settlement, and for borrowers and guarantors to guarantee.

8. Is the present banking system safe for human health?

No. Bright men should be able to see through such a corrupt banking system we have in place everywhere in the world.

9. Why can't someone study a non-corrupt banking system, that does not prey on unsuspecting men who want to be guarantors, who are oblivious about future problems of their actions?

The banking industry is the most corrupt of all industries. Men should try and avoid corrupt banking systems by not becoming guarantors. Down with the idea of guarantors. Find something better.

10. Are there better banking systems which are not taxing on men's health?

There should be. There must be one. It is up to the banking industry to find safer means of obtaining loan repayments, and one which has the least impact on men's health.

Tuesday, 19 December 2017

Cardiogenic shock secondary to anterolateral myocardial infarction

Topics to search:
Anterolateral MI
Cardiogenic shock
Emergency Medicine (eMedicine)

I have chosen this topic for this post because it is a real problem and a real cause of death. It happens even with the best care afforded. It happens and it runs in families. There are risk factors. There are clear signs to look out for. It is an end-point of a chronic disease process. It doesn't just appear out of the blue. So how do we go about picking out bits and pieces and learn about this condition?

I will write an abridged scenario. See if you can clearly see how the disease progressed from A to Z. This is a real case scenario that occurred on 16 December 2017.


A 60-year old Malay diabetic female with healed diabetic foot, cataract and partial sight felt fatigued following dialysis. She was brought to a Government hospital on 12 Dec 2017 at 8 pm, where she was warded on 13 Dec 2017 at 2 am. She was conscious. She was hospitalised for pulmonary emphysema with coughing and hypotension. She was treated and felt better the following day, 14 Dec 2017. However, her BP dropped to critical level and she was rushed to ICU, where BP was stabilised. She was still conscious. It was 15 Dec 2017.  Later in ICU, her BP dropped again and she suffered an extensive acute myocardial infarction (massive heart attack) at 10 am. She was rushed to CCU, where she became unconscious. Her condition worsened by 2 pm, and she suffered a cardiogenic shock. She passed away at 3:40 pm on 16 Dec 2017.

Here are some tough questions regarding the passage above.
  1. What is myocardial infarct/infarction (MI)?
  2. Why does MI occur?
  3. What are the causes of MI?
  4. Who are at risk of MI?
  5. What are diabetic complications?
  6. Will all diabetics die from MI?
  7. Will all diabetics suffer from cardiogenic shock?
  8. Can the patient be saved after MI?
  9. Can the patient still be saved after cardiogenic shock?
  10. Why does cardiogenic shock occur secondary to MI?
  11. Are there devices which can be used following MI?
  12. Which type of MI is fatal?
  13. What is STEMI?
  14. Which part on the heart does anterolateral aspect refer to?
  15. What is the cause of anterolateral MI?
  16. Which part of the coronary artery is occluded in anterolateral MI?
  17. Why is ECG essential in Emergency Medicine?
  18. How will ECG indicate anterolateral MI?
  19. What is cardiac aneurysm?
  20. When are visitors allowed to visit the unconscious patient in CCU?
  21. Who is allowed to visit patients in CCU?
  22. Is ICU or CCU a terminal place (for end of life)?
  23. Will every patient admitted to ICU or CCU never survive?
  24. Will surviving family members need counselling? For what & why?
  25. Can food cause diabetes? How & why?
  26. Can food cause heart disease? How & why?
  27. Can food kill?
  28. How much do you think a 5-day hospital stay as in this case would cost in Malaysia today?
  29. How much does dialysis cost today?
  30. How often do diabetics need dialysis?
  31. What are the physiological responses to hemodialysis that may cause intradialytic hypotension (IDH)?
  32. What are the complications following dialysis?
  33. Is dialysis essential?
  34. Are there risks with dialysis?
  35. What are medications for diabetics who need dialysis?
  36. How safe is dialysis today? Can dialysis cause death?
  37. What is the ICD-10 code for the scenario given above?

External links:

Acute anterolateral MI



Cardiac cycle

Cardiogenic shock




Friday, 10 November 2017

Computers in the Labs

Note: This is a postgraduate topic. I have included it here simply because I think it is best to introduce this topic early to medical students who have a keen interest in computers. They may think that they may have to forego their interest in computers when they take up medicine. They don't have to. Computers are widely used in Medicine today. This post is an introductory article about the use of computers in the clinical laboratory. There is a good review article in 2014 in the external links below that gives a clear overview of what is to come in the future. There is an article that highlights precautions when interpreting diagnostic tests and when using algorithms.

The computer revolution is among the fastest we have to date, competing with other revolutions in the car industry, electronics industry, weapons industry, space industry, drug discovery industry, food industry and fashion industry. There are countless industries going on and evolving, some which we fail to update ourselves with.

Let's look at computers. Where are we today with computers?

Malaysia is an ancient land mass, but a young developing nation. It is considered old enough, but young enough to still absorb new technologies. Malaysia has evolved and is still evolving. One of the fastest evolving industries in Malaysia today is the use of computers in its clinical laboratories (clinical labs).

The hospital and its associated labs

Some hospitals are big and some are small. Big established hospitals have at least 8 associated clinical labs and 8 specialist clinics in addition to the emergency rooms, day wards, hospital wards, recovery rooms and operation theatres. Let's not forget the mortuary.

Clinical labs

We will focus on the clinical biochemistry lab (USA), also called chemical pathology lab (UK). This may be lumped together with other disciplines and called pathology lab. We will focus on clinical biochemistry lab services.

Lab technologists

The people who perform the laboratory tests in clinical labs are referred to as medical laboratory technologists (MLTs), med techs, lab technologists or just technologists. They have undergone 4 years laboratory training in at least 8 clinical lab disciplines at a local university. They are diploma graduates. Their experiences working in the labs are most precious, but hardly tapped and discussed.

Number of tests

Each lab technologist performs many tests a day, on many instruments and chemistry analyzers in the lab. The technologists then enter the lab results (lab data) into the computers in the lab, or the computers capture lab results automatically.

The number of tests have increased as a result of 2 things - more tests are available now (bigger test selection) and more patients have come to hospital (better hospital awareness).

Big hospitals have well established clinical biochemistry labs which perform a minimum of 20,000 tests per month. As the number of tests have increased, so have the pressure to perform these tests on time and return the test results to the doctor on time.

Turnaround time (TAT)

Is there such a thing as 'right on time' or 'just in time'? That is a subjective notion. In the computerised clinical labs, every step of the workflow and work process is TIMED. Yes, everything is timed.

How is everything timed in the clinical lab? The patient is marked the minute he/she registers at the hospital counter. A set of barcodes is printed that tells his hospital details. It is his hospital ID and digital hospital bookmark. The barcode travels everywhere the patient goes in the hospital.

When his blood specimens are taken and sent to the lab for analysis, the blood sampling time and test requisition times are entered into the computer.

When the specimens reach the clinical lab, another time is stamped (arrival time). The the specimens are processed to obtain the samples needed for analyses. Sometimes the original tubes (primary tubes) are used on the analyzers, without a need for processing and tube transfer.

When the test results are ready, a time is recorded. The test results are conveyed to the computer system in the lab, and travels to the doctor who requested the test. However, the doctor may be away after hours or gone for 3 months's holiday. In this case, the computer system stores the test results till he returns to have a look at them. Or another doctor who is replacing him can take a look at the patient and the patient's data. This is fine.

The average turnaround time (TAT) for a clinical lab data is 1 hour. This means the doctor and the patient has to wait a minimum of 1 hour before the test results are ready. Why is it 1 hour and not less? How can it be less? It can't be less because it takes time to bring the specimen from the ward or clinic to the clinical lab. It takes time for the technologists to centrifuge and separate serum or plasma from blood, unless blood can be used for tests. It is takes time to perform a test. Once the results are ready, they have to be verified by a doctor in the clinical lab, before the same results are flash on the computer screen in the doctor's office.

Clinical chemical pathologists

Who are these people? The clinical chemical pathologists are doctors who have specialised in Chemical Pathology for their postgraduate master's degree. This postgraduate degree is called Master of Medicine in Chemical Pathology (MPath Chemical Pathology), or MPath Chem Path. It is highly sought as it enables the qualified doctor to work in the clinical chemical pathology lab.

Previously, scientists with PhD were running the lab as they have sufficient lab training and 10 years labwork or labbench experience. However, the Health Ministry (Kementerian Kesihatan Malaysia, KKM) had passed a memo that only doctors can run the clinical chemistry lab. So the MPath Chem Path doctors rule the lab. They verify the test results before the result are released to the doctors in the clinics and wards.

I think this is a waste of resources and untapped expertise as PhD are better trained at labwork and the Chemical Pathologists are better at interpreting the test results. They should be working side by side. Unfortunately, this is not the case. So this is a sad thing in reality.

Computers in the labs

Why are there computers in the lab? They are useless unless put to work effectively. The computers have to run on a suitable computer program (software). The computer program be designed and made in-house or bought off the shelf from a computer vendor. It all boils down to how much money the hospital is willing to invest in a computer system.


A complete computer system is expensive. Costs run from a minimum of RM1 million. Before the purchase is made, an intensive plan of action and numerous meetings and resolutions have been made. Once the decision made is to purchase, then everything must work according to plan (roll-out) until it is time to give the password and magic to the hospital administrator (actually the chief IT person).

Incurring expenses

Nothing runs well and the same for years. Things will breakdown. The computer cables may get chewed up by rodents in the roof and underground. Floods may soak and damage the computer cables. Fire may damage the cables. Too many cables criss-crossing all over the hospital can get mixed up and confused. Maintenance checks need to be in place. A backup system needs to be in place. The mess knows no end. Managing and maintaining a computer system for the hospital can be fun or otherwise. There are challenges.

Mark of excellence

The computer system is an expert system. It is a wonderful machine as it can do wonders. An in-house system that is flexible and expandable is better than a bought system that is restrictive but yet expandable with added cost. A hospital with a good IT team that can design, make, implement, run, manage, expand, rebuild, refine, rerun, ... its computer system is the best for any hospital to have. This IT team of the hospital can become the IT company and serve the wider community. It is bad if a vendor has to come in to offer a complete computer system for a public hospital. That is how I see things.

External links:

1. Test ordering (test requisition) / investigation protocols

(i) Inappropriate tests ordering by doctors vs what the lab thinks is appropriate

Antonin Jabor and Vladimir Palicka
Rational use of clinical chemistry investigations: form diagnoses to processes.
Ann Clin Biochem 1998 35: 351-353
Personal View

(ii) Static vs dynamic rules for investigative protocol for patients undergoing liver transplant

PG Nightingale, M Peters, D Mutimer, JM Neuberger
Effects of a computerised protocol management system on ordering of clinical tests.
Quality in Health Care 1999;3:23-28

2. Precautions in diagnostic data interpretation and when using algorithms

Mauro Panteghini
The Future of Laboratory Medicine: Understanding the New Pressures.
Clin Biochem Rev 2004 Nov 25(4): 207-215

3. Pathology & informatics 

Richard G Jones, Owen A Johnson, Gifford Batstone
Informatics and the Clinical Laboratory.
Clin Biochem Rev 35 (3) 2014: 177-193
Review Article

Hagenbichler E, Klinger D, Neuner L, Pfeiffer K-P
Automated computer-assisted evaluation of diagnosis-and-procedure-reports in Austrian hospitals.
Jorgerstr, 3/35, A-1170 Wien: AKH Linz, A-4020 Linz:
Inst. f. Biostatistik, Univ.-Klinik Innsbruck, A-6020 Innsbruck, Austria.
In: Medical Informatics Europe '99, edited by Peter Kokol, Biaz Zupan, Janez Stare

G. Stephens et al. Computerised resources.
In: Medical Informatics Europe '99, edited by Peter Kokol, Biaz Zupan, Janez Stare
  • OpenLabs (by St Jame's Hospital, Dublin)
  • Scoringprogramm Version 1.2 for 1997
  • Scoringprogramm Version 3.1 for 1999
  • Intensivscoringprogramm Version 2.1 for 1999 for ICU

Marjan Premik, Vladimir Mayer, Marina Kuzman, Miroslav Mayer
Bed Utilization Performances of Slovenian and Croatian Acute Hospital Systems.
University of Ljubljana, Faculty of Medicine, Institute of Social Medicine & Croatian National Institute of Public Health. In: Yates J. ed. Hospital Beds: A Problem for Diagnosis and Management? Heinemann Medical Books Ltd, London 1982, IV.
  • Calculating 4 hospital bed performance indicators:
  • length of stay: 365 * bed occupancy/discharges + deaths
  • throughput: discharges + deaths/available beds
  • turnover interval: (available beds - occupied beds) * 365/discharges + deaths
  • % bed emptiness: (available beds - occupied beds)/available beds * 100
  • The Barber-Johnson's method of pictorial representation of hospital bed use.

M.N. Sarkies, K.-A. Bowles, E.H. Skinner, D. Mitchell, R. Haas, M. Ho, K. Salter, K. May, D. Markham, L. O’Brien, S. Plumb, and T.P. Haines.
Data Collection Methods in Health Services Research.
Hospital Length of Stay and Discharge Destination.
Appl Clin Inform. 2015; 6(1): 96–109.
(Research article)

4. Microbiology & 'turnkey' systems

Paul Wolotsky
Clinical Laboratory Computer Systems
Proc Annu Symp Comput Appl Med Care 1979 Oct 17 : 550-551

Paul Wolotsky
Computerisation of Clinical Laboratories.
Proc Annu Symp Comput Appl Med Care 1979 Oct 17 : 552-557

C Block
Benefits and limitations of computerised laboratory data.
J Clin Pathol. 1997 Jun 50(6): 448-449

5. Consumer Protection

Austrian Federal Ministry of Labor, Social Affairs and Consumer Protection.

Monday, 6 November 2017

Retention of Basic Science Knowledge in Clinical Years

The undergraduate medical course is between 5 to 6 years. Basic Science knowledge is taught in first year. They comprise 3 cores subjects - Anatomy, Biochemistry and Physiology. Students have to be able to grasp and retain their knowledge in first year and be able to apply basic science knowledge in their clinical years. Are they able to do this effectively? How is their retention of Basic Science mastered and used in clinical years? What can we do to help students to effectively retains sufficient Basic Science knowledge for them to get through final year?

External links:

Tuesday, 24 October 2017

Diabetic Peripheral Neuropathy

Scenario 1
Diabetes can progress and worsen, with nerve involvement in the limbs and digits. Without normal innervation to the digits, the feet and toes feel tingling sensation. The toes can feel when touched, rubbed or squeezed, but they are abnormal.

Scenario 2
In the Malay context, there is avoidance by mothers in the post-partum period (dalam tempoh pantang), not to walkabout and to remain in bed as much as possible. This is to avoid having mothers accidentally kicked the door frame, especially the raised door frame on the floor (bendul). Accidentally kicking the door frame (or the door itself) can cause serious injury to the toes involved. The mother does not feel the tingling sensation immediately, but much later, and for a long period, until the toes are put right by proper massage and stretching techniques. Ignoring the problem will cause the mother to experience extreme pain while walking for long periods. What can be done to alleviate such problem?

Is there hope
Can nerves in the foot be put right once there is tingling sensation? It depends on what happened and the level of severity. If the toes look normal colour and the nails are growing fine, there is some hope. Occasional massage is good to maintain and encourage blood flow. But will the nerves regenerate?

What can be done?

  1. Massage the toes to reduce pain sensation. Some LMS will help. Menthol relieves pain (minyak angin). Tea tree oil is quite useful as it has menthol and the oil is good for massage.
  2. Stretch Use the hands and flex the toes up towards the body, hold and then release. Repeat a few times. Then flex the toes towards the floor to see if they feel better.
  3. Wiggle the toes while watching TV.
  4. Massage the thigh by pulling action, pull them up towards the body. This is correct the nerve and blood vessels to the toes. 
  5. Massage the affected foot before sleep. Use some oil to massage the thigh inward and upward towards the body. Raise the affected foot when sleeping. This will relieve pain in the thigh and affected foot. The thigh and foot will correct itself in about 2 days if done correctly. 

Pain and tingling sensation will return once in a while. Constant massage of the foot will help to keep the pain away and keep the foot alive. Blood vessels can regenerate and form new ones. The toes will maintain normal colour if there is blood flow. Nerves are difficult to regenerate but there is hope that they will generate given the right environment. Something to ponder upon.

External links

Monday, 16 October 2017

Beta-Thalassemia Major

  1. Hemoglobin was discovered by Hünefeld in 1840.
  2. Hemoglobin (Hb) is an iron-containing oxygen-transport metalloprotein in the red blood cells (rbc's) of all vertebrates (with the exception of the fish family Channichthyidae) as well as the tissues of some invertebrates.
  3. Hemoglobin has the formula C2952H4664O832N812S8Fe4. 
  4. Each hemoglobin molecule has 4 iron (Fe) atoms.
  5. The role of hemoglobin in the blood was elucidated by French physiologist Claude Bernard.
  6. Hemoglobin carries oxygen in the blood from the respiratory organs (lungs or gills) to the rest of the body (ie. the tissues). 
  7. Hemoglobin is red because it contains heme, which is a bright cherry red molecule.
  8. Hemoglobin is a bright cherry red molecule which can undergo oxygenation and deoxygenation reactions.
  9. Hemoglobin's reversible oxygenation was described a few years later (1851-1859) by Felix Hoppe-Seyler.
  10. Presence of oxygenated hemoglobin gives blood a bright red colour and the smell of fresh blood as present in hospital corridors.
  11. Presence of deoxygenated hemoglobin gives blood a dark red-brown colour and this blood stinks of dead bodies (corpses) if left to stand at room temperature.
  12. Cells and tissues require oxygen for aerobic glycolysis. Complete biological oxidation produces energy (ATP), carbon dioxide (CO2) and water (H2O).
  13. Hemoglobin + CO2 = carbaminohemoglobin. Carbaminohemoglobin carries carbon dioxide
  14. Hemoglobin is also found outside red blood cells and their progenitor lines. 
  15. Other cells that contain hemoglobin include the A9 dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, and mesangial cells in the kidney. In these tissues, hemoglobin has a non-oxygen-carrying function as an antioxidant and a regulator of iron metabolism.
  16. In 1959, Max Perutz determined the molecular structure of hemoglobin by X-ray crystallography.


Hemoglobin forms in the developing rbc (reticulocytes) in the bone marrow (BM).

Steps in heme & hemoglobin synthesis:
  1. Glycine + succinyl-CoA = delta-aminolevulinic acid (d-ALA)
  2. d-ALA exits into cytoplasm
  3. d-ALA is reacted upon by enzymes
  4. forms protoporphyrin
  5. protoporphyrin re-enters mitochondria
  6. Iron (Fe) is added to protoporphyrin
  7. forms heme
  8. Globin is made at ribosomes of rbc's and involves 2 chromosomes. Alpha globin chains are made by Chromosome 16. Beta globin chains are made by Chromosome 11.
  9. Heme + Globin = Hemoglobin
  10. Lead (Pb) is an inhibitor of heme and hemoglobin synthesis

  1. Hemoglobin helps to carry oxygen to body tissues.
  2. Hemoglobin helps to carry carbon dioxide for disposal by the lungs.
  3. Rbc's contain hemoglobin.
  4. The level of hemglobin in blood varies for males and females.
  5. Males perform more physical activities and have higher hemoglobin levels in blood.
  6. Females perform less physical activities and have lower hemoglobin levels in blood.
  7. Hemoglobin has a quaternary structure characteristic of many multi-subunit globular proteins.
  8. There are 4 types of globin chains: alpha (a), beta (b), delta (d) and gamma (g)
  9. Hemoglobin consists of 4 subunits: 2 alpha globins + 2 beta/delta/gamma globins
  10. Fetal hemoglobin is Hb F.
  11. Adult hemoglobins are Hb A1 and Hb A2
  12. Hb A1 = a2 b2 (alpha2 beta2)
  13. Hb A2 = a2 d2 (alpha2 delta2)
  14. Hb F = a2 g2 (alpha2 gamma2)
  15. Hemoglobin can be saturated with oxygen molecules (oxyhemoglobin), or desaturated with oxygen molecules (deoxyhemoglobin).

  1. A globin chain is a polypeptide.
  2. The amino acid sequence of a globin chain is determined by DNA sequences called genes.
  3. There are 4 globin chains: alpha (a), beta (b), delta (d) and gamma (g)
  4. Different globin chains are synthesized at different times during fetal development and till adult stage.
  5. There is more than one hemoglobin gene.
  6. The main form of hemoglobin present in adult man is hemoglobin A (HbA).
  7. In humans, hemoglobin A is coded for by the genes, HBA1, HBA2, and HBB.
  8. Hemoglobin contains 2 alpha globin chains and 2 beta, 2 delta or 2 gamma globin chains
  9. Thus, many configurations of globin chains are possible:
  10. Hb A1 = a2 b2 (alpha2 beta2) (heterotetramer, α2β2)
  11. Hb A2 = a2 d2 (alpha2 delta2)
  12. Hb F = a2 g2 (alpha2 gamma2) (HbF, α2γ2)
  13. Fetal hemoglobin is Hb F.
  14. Adult hemoglobins are Hb A1 and Hb A2
  15. Normal hemoglobin types found in adults are; 
  • Hemoglobin A (Hb A), which is 95-98% of hemoglobin found in adults, 
  • Hemoglobin A2 (Hb A2), which is 2-3% of hemoglobin found in adults, and 
  • Hemoglobin F (Hb F), which is found in adults up to 2.5%. It  is the primary hemoglobin that is produced by the fetus during pregnancy.
     16. In the embryo:
  • Hb Gower 1 (ζ2ε2)
  • Hb Gower 2 (α2ε2)
  • Hemoglobin Portland I (ζ2γ2)
  • Hemoglobin Portland II (ζ2β2).

     17. In the fetus: Hemoglobin F 2γ2

      18. After birth:
  • Hemoglobin A 2β2) – The most common with a normal amount over 95%.
  • Hemoglobin A2 2δ2) – δ chain synthesis begins late in the third trimester and, in adults, it has a normal range of 1.5–3.5%.
  • Hemoglobin F 2γ2) – In adults Hemoglobin F is restricted to a limited population of red cells called F-cells. However, the level of Hb F can be elevated in persons with sickle-cell disease and beta-thalassemia.

    19. Variant forms that cause disease:
  • Hemoglobin D-Punjab – (α2βD2– A variant form of hemoglobin.
  • Hemoglobin H (β4– A variant form of hemoglobin, formed by a tetramer of β chains, which may be present in variants of α thalassemia.
  • Hemoglobin Barts (γ4– A variant form of hemoglobin, formed by a tetramer of γ chains, which may be present in variants of α thalassemia.
  • Hemoglobin S (α2βS2– A variant form of hemoglobin found in people with sickle cell disease. There is a variation in the β-chain gene, causing a change in the properties of hemoglobin, which results in sickling of red blood cells.
  • Hemoglobin C (α2βC2) – Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia.
  • Hemoglobin E (α2βE2– Another variant due to a variation in the β-chain gene. This variant causes a mild chronic hemolytic anemia.
  • Hemoglobin AS – A heterozygous form causing sickle cell trait (SCT) with one adult gene and one sickle cell disease gene
  • Hemoglobin SC disease – A compound heterozygous form with one sickle gene and another encoding Hemoglobin C. Hemoglobin Hopkins-2 - A variant form of hemoglobin that is sometimes viewed in combination with Hemoglobin S to produce sickle cell disease.

      20. List of known hemoglobin variants
  • Hb Kansas
  • Hb S
  • Hb C
  • Hb E
  • Hb D-Punjab
  • Hb O-Arab
  • Hb G-Philadelphia
  • Hb Hasharon
  • Hb Lepore
  • Hb M
  • Hb F
  • Hb Hope
  • Hb Pisa
  • Hb J
  • Hb N-Baltimore

  1. Fetal hemoglobin (HbF, α2γ2) is found in the developing fetus, and binds oxygen with greater affinity than adult hemoglobin A.
  2. Hemoglobin F (Hb F) is the primary hemoglobin that is produced by the fetus during pregnancy.
  3. The levels can be normal to increased in beta thalassemia. 
  4. Hemoglobin F frequently increases in individuals with sickle cell anemia and sickle cell-beta thalassemia. 
  5. Individuals with sickle cell and increase of Hb F have a milder case of the disease. 
  6. There are situations where the Hb F is increased. This rare condition is called Hereditary Persistence of Fetal Hemoglobin (HPFH).
  7. HPFH is a group of disorders where the Hemoglobin F is increased without signs or clinical features of thalassemia. 
  8. Some different ethnic groups have different mutations that cause HPFH. 
  9. Hb F can also be increase by acquired conditions that involve the red blood cells. 
  10. Elevated Hemoglobin F levels are also associated with Leukemia and myeloproliferative disorders.

  1. Hemoglobin H (Hb H) increases the affinity for oxygen. 
  2. Hb H holds onto the oxygen instead of releasing it into tissue and cells. 
  3. Hb H usually occurs in some alpha thalassemia and is composed of four beta globin (protein) chains (beta tetramer, β4). 
  4. This variant is usually produced in response to a severe shortage of alpha chains, and usually cause beta chains to function abnormally.

  1. Hemoglobinopathy is a hereditary condition involving an abnormality in the structure of hemoglobin.
  2. Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants. Many of these mutant forms of hemoglobin cause no disease. Some of these mutant forms of hemoglobin, however, cause a group of hereditary diseases termed the hemoglobinopathies. The best known hemoglobinopathy is sickle-cell disease (SCD).
  3. Hemoglobin variants are a part of the normal embryonic and fetal development. They may also be pathologic mutant forms of hemoglobin in a population, caused by variations in genetics. Some well-known hemoglobin variants, such as sickle-cell anemia (SCA), are responsible for diseases and are considered hemoglobinopathies. Other variants cause no detectable pathology, and are thus considered non-pathological variants.
  4. Thalassemia is a reduced or no production of a or b globin chain. The a and b globin chains have normal structures.

  1. Hemoglobin carries oxygen to tissues.
  2. Hemoglobin carries carbon dioxide back to the lungs for expulsion (expiration).
  3. Hemoglobin is not synthesized (made) in red blood cells (erythrocytes).
  4. Hemoglobin synthesis occurs in nucleated reticulocytes.
  5. Hemoglobin synthesis is regulated (controlled).
  6. Erythrocytes have a half-life of 120 days (ie they survive approximately 120 days before they are cleared from the blood circulation).
  7. When old erythrocytes are removed and broken down, hemoglobin in them too is broken down (degraded).
  8. New hemoglobin will need to be synthesized to replace that lost.
  9. If hemoglobin synthesis is slowed (or lags behind), there will be either insufficient hemoglobin, lack of hemoglobin or defective hemoglobin in the erythrocytes.

  1. Thalassemias are a group of genetic blood disorders 
  2. Thalassemias are inherited blood disorders
  3. Thalassemia patients make normal globin chains, but at reduced rates
  4. These blood disorders have defective production of hemoglobin
  5. The thalassemias are autosomal recessive disorders which result in reduced production of one or more of the subunits of hemoglobin
  6. There are 2 forms of thalassemia: alpha- and beta-thalassemia
  7. There are two forms of beta-thalassemia: thalassemia minor and thalassemia major (also called Cooley's anemia)

  1. Reduced production of alpha globin chains
  2. Results from gene deletion
  3. Alpha-thalassemias have reduced production of alpha-globin chains to make new hemoglobin
  4. The resulting hemoglobin molecule has either 1 or no alpha-globin chain; 
  5. The resulting hemoglobin configuration can be b2 or ab2, which are defective hemoglobins.
  6. Hemoglobin with b2 configuration occurs in alpha-thalassemia major.
  7. Hemoglobin with ab2 configuration occurs in alpha-thalassemia minor.

  1. The alpha globin gene is present on Chromosome 16.
  2. Alpha thalassemia results from gene deletion.
  3. ONE alpha globin gene deletion is asymptomatic.
  4. TWO alpha globin gene deletions, can be either from the same chromosome (cis deletion) or from different chromosomes (trans deletion)
  5. Cis deletion is worse than trans deletion. 
  6. Inheritance of cis deletion from both parents by the offspring is dangerous as it results in severe alpha thalassemia (no alpha globin chain).
  7. THREE alpha gene deletions results in Hb H, with b2 dimer and b4 tetramer.
  8. FOUR alpha gene deletions results in Hb Bart's, with g4 tetramer.

  1. alpha carrier and Hb H don't need treatment as they are fine.

  1. Reduced or no production of beta globin chains
  2. It is genetically determined
  3. The beta globin gene is located on a chromosome 11 (ie an autosome, not a sex chromosome, not X or Y)
  4. Two copies are derived in the child, one from the father, and one from the mother
  5. Each chromosome has an allele for beta globin
  6. Each allele codes for beta globin chain, one from the father, one from the mother
  7. Beta thalassemia also occurs as a result of gene mutation 

  1. There are 2 types of beta globin gene mutations: B+ and B0
  2. In B+ gene mutation, the gene is capable of producing beta globin chain even though at reduced rate; there is some production of beta globin chain
  3. In B0 mutation, the gene is incapable of producing beta globin chain; there is no production of beta globin chain
  4. Possible genetic combinations are thus: B+B+, B+B0, B0B+, and B0B0
  5.         B+B+ = produce beta globin chain .... beta thalassemia major
  6.         B+B0 or B0B+  = produce beta globin chain ... beta thalassemia minor
  7.         B0B0 = do not produce beta globin chain .... beta thalassemia major

  1. Beta-thalassemias are of 2 types - thalassemia major and thalassemia minor
  2. Thalassemia major is also called Cooley's anemia
  3. Production of beta-globin chain of hemoglobin is reduced or none
  4. The resulting hemoglobin molecule has either a2 or a2b, which are hemoglobins with reduced beta globin or no beta globin
  5. Hemoglobin with a2 configuration occurs in beta-thalassemia major.
  6. Hemoglobin with a2b configuration occurs in beta-thalassemia minor.
  7. Beta thalassemia minor is a2BB+ with mild anemia and increased Rbc count
  8. Beta thalassemia major is a2B+B+ or a2B0B0 with severe anemia and increased Rbc count
  9. In B0B0, there is no beta globin production; there will be excess alpha globin chains
  10. When there is no beta globin production, and there is excess alpha globins, 4 alpha globin chains combine to form an alpha globin tetramer, which in turn forms ineffective hemoglobin. This results in ineffective erythropoiesis.

  1. When rbc count is low, the bone marrow compensates by producing more rbc's.
  2. Rbc's with alpha globin tetramers (a4) are abnormal and are destroyed while still in the bone marrow.
  3. Any rbc's with alpha globin tetramers (a4) that escaped from the bone marrow and are released into the circulation, are trapped by the endothelial system (eg  spleen) and are destroyed, thus removing them from the systemic circulation ... leading to anaemia.
  4. Any rbc's containing alpha4 tetramer will be destroyed ... leading to anaemia.
  5. When the body senses a rapid reduction in rbc count, it tries to makes more rbc's in the bone marrow.
  6. The bone marrow will become hyperactive in order to make rbc's.
  7. The bone marrow is now hyperactive ... trying to make a lot of new rbc's even though beta globin synthesis is reduced.
  8. When the bone marrow is active and increasing its mass (expanding), it compresses the cortex, thus thinning the cortex.
  9. The thick cortex gives bone strength. Once the cortex is thinner, bone strength is reduced and the bones are weakened, and can possibly lead to pathological fracture. This can happen in thalassemia patients. The body will try to produce rbc's using all the bone marrow in the body.
  10. Normally after birth, erythropoiesis is limited to a few bones - bone marrow of the central bones - of the skull, ribs, vertebra and a few long bones, ribs. However, in beta thalasemia with anemia, almost all bones with bone marrow will try to make rbc's.
  11. As a result, when the bone marrow cavity expands rapidly to produce more rbc's in the skull and the cortex thins, the skull marrow will crack, giving a hair-on-end or crew cut appearance. Expansion of the bone marrow of the face will give a chipmunk appearance. These are findings in thalassemia patients.

  1. Parvovirus P19 infection halts rbc production for 1-2 weeks in normal healthy persons, as we have a large reserve of rbc's.
  2. However, in beta thalassemia major patients, Parvovirus P19 infection is dangerous. They hardly have any rbc reserve and need all the rbc's in the bone marrow.

  1. The Indians are classified as Caucasanoids. They are Aryans of Italian and Greek origins. Thus, they inherit beta-thalassemia from their Mediterranean ancestors.
  2. The Malays of Indian heritage also inherit beta-thalassemia from their Indian Mediterranean ancestors. Beta-thalassemia is common among this Malay population in Malaysia.

  1. Anaemia
  2. Manifestation of increased hemopoiesis in face and skull
  3. Extramedullary hemopoiesis in liver and spleen results in nucleated rbc's
  4. Hepatosplenomegaly

  1. fatigue, weakness, or shortness of breath
  2. a pale appearance (pallor) or a yellow color to the skin (jaundice)
  3. irritability
  4. deformities of the facial bones
  5. slow growth (retarded growth, short for stature)
  6. a swollen abdomen
  7. dark urine

  1. Microscopy
  2. Skull radiography
  3. Hemoglobin

  1. The microscope is the best way to examine erythrocyte appearances.
  2. Erythrocytes with insufficient or deficient hemoglobin will not look normal when examined under the microscope.
  3. Microscopic findings are diagnostic.
  4. Pale erythrocytes point to anemia.
  5. "Mexican hats" or target cells (or targets) point to thalassemia.
  6. Small erythrocytes (microcytic) point to iron deficiency - microcytic anemia.
  7. Big pale erythrocytes (macrocytic) point to vitamin B deficiency - macrocytic anemia.
  8. Spiky erythrocytes (echinocytes) have spike-like projections on their surfaces.
  9. Spindle-shaped erythrocytes
  10. Sickle-shaped erythrocytes occur in sickle cell anemia (SCA)
  11. Extramedullary hemopoiesis (occurs in liver and spleen) will lead to nucleated rbc's.
  12. Liver and spleen are not equipped to make rbs'c. So these organs will make immature nucleated rbc's which are seen in the circulation.
  13. Microcytic hypochromic anaemia
  14. Normal rbc's are round biconcave discs, with 2/3 red due to hemoglobin and 1/3 pale due to less hemogloin
  15. Target cells are seen thalassemia. Target cells lack tensile strength and rbc biconcavity has blebs (outgrowths) and are filled with hemoglobin. The rbc's now look like target cells, like bull's eye

  1. Blood transfusion. Blood transfusion bags contain iron (Fe); 1 bag = 250 mg iron. When we transfuse patients at 4 weeks interval, we also supply them with extra iron (blood > rbc > Hb > rbc's are degraded in 120 days and free iron is released). Iron has no specific way for excretion. So iron is deposited in tissues, leading to hemosiderosis or hemochromatosis. So, iron overload results. A lot of problems thus result.
  2. Iron chelation therapy

External links



Hemoglobin variants