Gall Stones

Gall stones have become a common issue in the medical field.

It is strongly influenced by age and sex with genetics playing a role as well. The risk increases with age and is two times higher in female.

Before continuing any further, a small description on the anatomy and the functions of Gall Bladder.

Gall bladder is nothing but a small organ lying in the inferior part of the liver in a space carved in liver for gall bladder. It is used just for the purpose of storage of bile which is produced in the liver.

What is bile?

Bile is a dark green fluid formed in the liver and it assists the digestion of lipids in the small intestine. It consists of water, electrolytes, bile acids, cholesterol, phospholipids and conjugated bilirubin. It is actually synthesized in hepatocytes from cholesterol. Approximately around 600ml of bile flow per day. When a person is fasting, half the bile flows directly into the duodenum and the other half into the gall bladder. After a meal, cholecystokinin is secreted by the duodenal mucosa and this stimulate the contraction of the gall bladder and relaxation of the sphincter of oddi, in turn the bile returns into the duodenum.

Cholecystokinin

Increases contraction of the Gall Bladder

Decrease the resistance of the sphincter of oddi

Stimulate flow of biliary contents into duodenum

Formation of Gall Stones:

Gall stones are of two types:

1. Cholesterol stones

2. Pigment stones

Cholesterol Gall stones:

It is due to the fact that the cholesterol in the bile becomes crystallized. It is promoted by three main factors:

1. Super saturation of cholesterol in bile which means the cholesterol ratio in bile is increased. It may occur in association with obesity, increased caloric or cholesterol rich diet, drugs (clofibrate).

2. Factors that promote crystallisation of the bile are increased. So what are those factors? Increased cholesterol level compared to bile acids & Decrease bile acid content. In addition, Cholesterol is not just derived from dietary source but is also synthesized within the liver. Cholesterol is formed in the liver in which the reaction is first catalysed by HMG-CoA reductase. Cholesterol is co-secreted with phospholipids into the biliary canaliculi. Thus when cholesterol level is increased by increased activity of HMG-CoA reductase, then the bile will be super saturated with cholesterol which will result in crystallisation. One form of drug to decrease blood cholesterol is produced in the form of HMG-CoA reductase inhibitors.

3. Motility of the gall bladder i.e. if the gall bladder contracted well to empty all the bile with super saturated cholesterol, then no stones will form. Hence hypomotility of the gall bladder acts a promoting factor.

There are also other conditions that promote the development of cholesterol stones.

Pregnancy in which there is decreased contractility of the gall bladder and super saturation of cholesterol.

Rapid weight reduction increases the risk of developing gall stones.

Pigment stones:

Pigment stone consists of Calcium bilirubinate with less than 50% cholesterol content.

There are two types black and brown.

Black pigment gallstones are formed in a network of Calcium bilirubinate with calcium carbonate and/or calcium phosphate. They are mostly seen in patient with haemolytic condition such as sickle cell disease and hereditary spherocytosis in which there is excess production of bilirubin.

Brown pigment gallstones are composed of calcium salts of fatty acids with calcium bilirubinate. These stones are more common in case of bile stasis and /or biliary infection.

Clinical presentation:

Usually they are asymptomatic. If the stone gets obstructs the cystic or common bile duct when migrating from the gall bladder, it causes severe pain which is termed as ‘ biliary colic’.

Pain usually increases after a meal with high fat content and is more pronounced during the mid-evening and early hours of the morning. Pain as a rule presents itself in the epigastrium and the right upper quadrant with radiation to the right shoulder and right subscapular region.Pain could be accompanied with nausea and vomiting. If there is fever and rigors, it advocates secondary complications such as cholecystitis, cholangitis or gall stone related pancreatitis.

Acute cholecystitis could result if there is obstruction to the gall bladder emptying. This is caused when the gall bladder cannot empty the bile duct and results in enlargement of the gall bladder. This enlargement would result in compromise of the blood supply. Due to the vascular events, infection ensues. The clinical features are same as that of biliary colic but the pain tends to be more severe, with peritoneal involvement, tenderness and muscle rigidity.

How to diagnose gall stones?

1. Alkaline phosphatase and bilirubin are elevated.

2. Abdominal ultrasound

3. Iodida scintiscan is used to visualise blockage of cystic duct with the bile duct.

4. In case of acute cholecystitis leuckocyte count will be increased with increased inflammatory markers.

How to treat Gall stones?

1. Cholecystectomy is the cure for any one with the complaints of gall stones. Nowadays we use the laparoscopic approach which has resulted in a faster recovery, decrease complication both from the operation and anaesthesia. In case of acute cholecystitis first treatment is nil by mouth, intravenous fluids, analgesics and intravenous antibiotics. Cholecystectomy is done only when the symptoms resolves. Complication of cholecystectomy is biliary leak from cystic duct or gall bladder bed. After few months of cholecystectomy or later there will be right upper quadrant pain. This is related to functional large bowel disease with colonic spasm at the hepatic flexure.

2. In some cases where surgery cannot be performed, cholesterol stones can be dissolved by increasing the bile salt content of bile. Chenodeoxycholic acid and ursodeoxycholic acid are used, which increases the bile content. But we must also consider the motility of the gall bladder and the stone must not be bigger than 10mm. Drugs like HMG CoA reductase inhibitors (simvastatin) can be added to decrease the cholesterol content.

3. Extracorporeal shock wave lithotripsy in which waves are passed directly by radiologically or by ultrasound on to gall bladder stones. The significant part in both the above mentioned case is that gall bladder function has to be intact.

Treatment of Hypertension

Our cardiology professor always insists us that significant part is not to prescribe drugs to the patient but to make sure he has a contribution from his part. Patients’ part is to straighten up things possible by diet and physical activity.

Part played by the patient to take control of the hypertension

1. Gather all possible information about hypertension. One does not have to master himself on hypertension. But make sure you know the cause, prevention and the treatment modalities i.e. combination of diet, physical activity + drugs prescribed by your doctor.

2. Be certain about what you eat. Do no gobble up everything. You must be aware of your diet. What do your breakfast, lunch and dinner mean to your body? Does it just fill your stomach or does it really have a positive impact on your health. When you eat healthy, your body will feel it. Read the contents of the food you buy. How much is added carbohydrate, Fat, Protein etc. Decrease the salt intake. Avoid junk food, fried food, refined food, salt and sugar. Add olives to your meal. Make simple changes in your cooking style. Use not much oil. Include fruits, vegetables, fish & nuts. There are many websites that give you in detail about what to eat and what not to eat. Make sure you don’t eat food that increases your blood cholesterol.

3. Physical Activity plays a major role. It will keep you fit and your weight in control. There are many physiological regulations that are controlled by physical activity which provides a life saving support for the human body. There are many miracles that physical exercise could do but these are not proven scientifically but you will feel the change in your body when you do it.

4. Sleep deprivation and stress has a great influence in increasing the blood pressure. It is sensible not to disturb your sleep. Sleep and stress acts in a vicious circle. If one has sleep disturbances, the next day he is going to be snappy and will end up with a stressful day. In other case if someone is stressed due to some problem, he will not get good sleep. So better to avoid both. Try some yoga, walk in fresh air, listen to good music, read good books, make your time worthwhile, try to help someone in real need which would really ease your aches.

There is no scientific evidence about the above mentioned but I can assure you it will have a dramatic change in the progression of the disease.

Following are the elements that determine the prognosis of hypertension

· Level of blood pressure

· Target organ damage

· Presence of other disease such as diabetes mellitus, cardiovascular disease, hyperlipidaemia, smoking, male sex)

· Age

· Life style which includes how good you are in maintaining relationships, your diet, activities etc.

Part played by medicine prescribed by the doctor:

Every country has its own Blood pressure threshold, to start the drug therapy. For example some countries starts therapy when the blood pressure is >160mmHg systolic and diastolic >100mmHg and in some treatment is started with systolic >140mmHg and diastolic >90mmHg. But it is best when the treatment is started at the earliest 140/90mmHg.

The aim of drug therapy is to decrease the complication of increased blood pressure and to prevent further progression.

There is no first line therapy as every individual have different drugs suitable for one self.

Diuretics:

This group consists of number of sub groups depending on the place of action in the kidney.

Thiazides:

It consists of

Bendroflumethazide

Cyclopenthiazide

Side Effects: Increases serum cholesterol, impairs glucose tolerance, Increases uric acid and hypokalemia (decreases potassium).

Loop diuretics:

Furosemides

Ethacrynic acid

Side Effects: Increases serum cholesterol, impairs glucose tolerance, increases uric acid and hypokalemia

Aldosterone Antagonists:

Spiranolactone

Epelerenone

Side Effects: Hyperkalemia (increases potassium), kidney failure.

Indication: Hyperaldosteronism

Potassium Retaining:

Amiloride

Side Effects: Renal failure, Hyperkalemia

All the above mentioned is indicated during heart failure and renal failure. The mechanism is organised through increased release of sodium in urine.

Beta Blockers:

Cardioselective

Atenolol

Metaprolol

Non selective

Propranolol

Combined alpha/beta

Labetalol

Carvedilol

Side effects: Asthma, COPD, 2^nd or 3^rd degree heart block, sick-sinus syndrome.

Indication: Effective in patient with tachycardia

These drugs are activated by acting on sympathetic nervous system and the rennin-angiotensin system. It decreases cardiac output, heart rate and cardiac contractility.

Alpha antagonist

Selective

Prazosin

Doxazosin

Terazosin

Non-selective

Phenoxybenzamine- used in phaeochromocytoma

Angiotensin-converting enzyme inihibitors:

Captopril

Lisinopril

Ramipril

Side Effects: dry cough, angiodema

Indication: Heart Failure, Diabetic nephropathy

These ACE inhibitors block the angiotension converting enzyme which results in decreased production of aldosterone which in turn results in increased excretion of sodium in urine.

Angiotensin II receptor antagonist

Losartan

Valsartan

Candesartan

Irbesartan

Indication: Heart failure, Diabetic nephropathy, cough (side effect of ACE inhibitors)

The above mentioned drugs work by acting on the Renin-Angiotensin-Aldosterone system .

Calcium Channel blockers

Dihydropyridines

Nifedipine

Side Effect: Flushing, Headache, sweating, swelling of ankles, palpitation

Indication: Angina

Non-dihydropyridines

Diltiazem Verapamil

Side Effect: Flushing, Headache, sweating, swelling of ankles, palpitation

Indication: Angina, Post myocardial Infarction, supraventricular tachycardia

These drugs acts causes decrease in blood pressure by causing dilation of vessels and reduce the force of heart contraction. This blocks the calcium channel which causes constriction of blood vessels.

There are other centrally acting drugs such as reserpine, methyldopa and clonidine.

There are also other vasodilators such as hydralazine and minoxidil which helps in case when the patient is resistant to other forms of drugs. Hydralazine may be involved with tachycardia, fluid retention and a systemic lupus erythematosus-like syndrome.

Sodium nitroprusside is also a potent arterial and venous dilator. It is used in hypertensive crisis.

Every treatment must have a goal. Here the aim is to maintain a systolic blood pressure <140mmhg>

Malignant hypertension:

This is characterised by elevated blood pressure (diastolic>140mmHg) along with damage of organs like kidney, eyes, brain and heart. In this case the drug of choice is intravenous nitroprusside and the blood pressure must be reduced very slowly.

Hypertension is the foot of many other disorders. The key to control is not far from us, but just next to us. Will see you in the next post with another interesting disease.

Hypertension

What is increased blood pressure? When there is resistance in the blood vessel to the flow of blood then the blood vessel has to increase its pressure to allow the blood to pass through.

There are many factors that influence the development of hypertension (increased blood pressure). It could be genetics or environmental. Factors include increased Nacl (salt) intake, alcohol consumption, psychosocial stress, obesity and low levels of physical activity.

There are two forms of hypertension:

Essential hypertension – influenced by the above risk factors and is not caused by any organ damage and does not have any definite cause. Hence it is said to be idiopathic hypertension.

Secondary Hypertension- influenced by disease of a particular organ. For example Renal disease is 80% cause of secondary hypertension, Endocrine causes including Conn’s syndrome, Adrenal Hyperplasia, Phaeochromocytoma, cushing’s syndrome, Acromegaly, Cardiovascular causes, drugs and pregnancy.

When is one said to have hypertension? (Increased blood pressure)

Two or more reading must have increased blood pressure in two or more outpatient visits. The blood pressure reading of threat can differ from patient to patient.

Hence it can be defined as the blood pressure measurement of an individual where treatment is necessary to control the adverse effects of increased blood pressure.

Blood Pressure Classification	Systolic, mmHg	Diastolic, mmHg
Normal	<120	and <80>
Prehypertension	120–139	or 80–89
Stage 1 hypertension	140–159	or 90–99
Stage 2 hypertension	160	or 100
Isolated systolic hypertension	140	and <90>

Source: Fauci As, Kasper DL, Braunwald E, HauserSL, Longo DL, Jameson JL, Loscalzo : Diabetes Mellitus in Harrison’s principles of Internal medicine, 17^th edition

How to measure blood pressure?

Sphygmomanometer is the device used to measure blood pressure. We have different methods for measurement of blood pressure.

An individual is said to have white coat hypertension when the increase in pressure is due to anxiety to the patient caused by the examination of the patient by medical staffs.

In that case patient could opt for an ambulatory blood pressure monitoring (day and night) i.e. blood pressure can be measured throughout the day and night at home.

Blood pressure is usually increased in the morning and decreased at night. This is the reason of increased prevalence of myocardial infarction (heart attack) and stroke occurring during the early hours of morning.

Most common causes of hypertension:

Systolic Hypertension with Wide Pulse Pressure

1. Decreased vascular compliance (arteriosclerosis) 2. Increased cardiac output a. Aortic regurgitation b. Thyrotoxicosis c. Hyperkinetic heart syndrome d. Fever e. Arteriovenous fistula f. Patent ductus arteriosus

Secondary Causes of Systolic and Diastolic Hypertension

Renal Parenchymal diseases, renal cysts (including polycystic kidney disease), renal tumors (including renin-secreting tumors), obstructive uropathy Renovascular Arteriosclerotic, fibromuscular dysplasia Adrenal Primary aldosteronism, Cushing's syndrome, 17-hydroxylase deficiency, 11-hydroxylase deficiency, 11-hydroxysteroid dehydrogenase deficiency (licorice), pheochromocytoma Aortic coarctation Obstructive sleep apnea Preeclampsia/eclampsia Neurogenic Psychogenic, diencephalic syndrome, familial dysautonomia, polyneuritis (acute porphyria, lead poisoning), acute increased intracranial pressure, acute spinal cord section Miscellaneous endocrine Hypothyroidism, hyperthyroidism, hypercalcemia, acromegaly Medications High-dose estrogens, adrenal steroids, decongestants, appetite suppressants, cyclosporine, tricyclic antidepressants, monamine oxidase inhibitors, erythropoietin, nonsteroidal anti-inflammatory agents, cocaine Mendelian forms of hypertension

Source: Fauci As, Kasper DL, Braunwald E, HauserSL, Longo DL, Jameson JL, Loscalzo : Diabetes Mellitus in Harrison’s principles of Internal medicine, 17^th edition

Factors influencing blood pressure

Blood pressure is determined by

Cardiac output * Peripheral resistance (resistance of blood vessel)

1. Cardiac output - It is the amount of blood pumped by the heart (ventricle) in one minute.

Cardiac output = Heart Rate * Stroke volume

Heart Rate - Number of heart beats per unit time

Stroke volume- Volume of blood pumped from ventricle with each beat

2. Peripheral resistance - It is the resistance of the blood vessel to the flow of blood which must be overcome to allow normal flow.

It is manipulated by the structure of the blood vessel and function of the vessel.

Mechanism involved in hypertension:

Increased intravascular volume

Extracellular fluid - Interstitial space and Blood plasma.

Fluid is always attracted towards the hypertonic space i.e. space which is rich in electrolytes will attract the fluid towards it. As sodium is the major component of extracellular fluid, when for some reason the sodium in blood is increased the fluid from intracellular space is moved into the extra cellular space. This increases the volume in the extracellular space.

There will be an increased in the cardiac output due to the expanding intravascular volume. To allow normal volume of blood, organs including kidney and brain starts to auto regulate the amount of blood by increasing the peripheral resistance of the blood vessel. As the peripheral resistance increases, cardiac output returns to normal. This increased sodium may be due to increased reabsorption of sodium in renal tubules.

Autonomic Nervous system

This maintains the blood pressure by sensing the pressure, volume and chemoreceptor signals. Adrenergic system controls the blood pressure by stimulating the secretion of Epinephrine, Norepinephrine and dopamine.

In Aorta and Carotid sinus, we have baro receptors which sense the change in the pressure in the artery and act accordingly. When there is increased arterial pressure, then the sympathetic flow is decreased which lessens the arterial pressure.

Renin-Angiotensin-Aldosterone

Renin is a protease secreted from juxtaglomerular cells(afferent arteriole of kidney). It facilitates the reasborption of sodium in the renal tubules by the production of aldosterone. It is stimulated by three mechanisms

Vascular Mechanisms:

The radius and the changeability of the vessels determine the arterial pressure. These two play a role in increasing arterial pressure.

Changes that occur in organs due to high blood pressure:

Heart:

Just hypertension can lead to death of a patient with hypertensive heart disease. It leads to left ventricular hypertrophy, chronic heart failure, diastolic dysfunction, abnormal flow of blood in an atherosclerotic artery and cardiac arrhythmia.

Brain:

Hypertension is an important risk factor for brain infarction and haemorrhage (bleeding). Cerebral flow is always unchanged by a process called auto regulation. When this auto regulation fails, this can lead to hypertensive encephalopathy.

Kidney:

Kidney diseases are the most common reason for hypertension but hypertension of some other origin can effect kidney and lead to end stage renal failure. Macroalbuminuria and microalbuminuria are the first indicator of kidney dysfunction

Peripheral artery:

Hypertension results in intermittent claudication (pain during walking) which is relieved by rest.

How to assess a patient with hypertension?

Reaching the necessary evidence is based on doctors’ talent to search out for the medical history. We must consider all possible symptoms like sweating, headaches, palpitations, breathlessness, chest pain, visual disturbances, and transient loss of consciousness. The above mentioned symptoms give significant clues and play a main role in diagnosis. Usually high blood pressure is diagnosed when an individual go for a random check up. So it is necessary for the patient and the doctor to discuss each and every symptom.

The following must be considered before continuing further:

-Duration of hypertension.

-Treatment undergone and any side effects from drugs.

-Take notice of any symptoms including insomnia, weakness of extremity muscles, snoring, symptoms of hypo and hyperthyroidism.

-Occurrence of any other systemic disease such as renal disease, diabetes mellitus & cardio vascular disease.

-Risk factors such as smoking, obesity, physical activity, and diabetes mellitus must be considered.

-After a thorough history taking and physical examination is performed the following lab analysis must be undertaken.

System	Test
Renal	Microscopic urinalysis, albumin excretion, serum BUN and/or creatinine
Endocrine	Serum sodium, potassium, calcium, ?TSH
Metabolic	Fasting blood glucose, total cholesterol, HDL and LDL (often computed) cholesterol, triglycerides
Other	Hematocrit, electrocardiogram

Source: Fauci As, Kasper DL, Braunwald E, HauserSL, Longo DL, Jameson JL, Loscalzo : Diabetes Mellitus in Harrison’s principles of Internal medicine, 17^th edition

Next blog will follow up with treatment principles of hypertension and about malignant hypertension.