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We are all guilty of pushing ourselves too hard and burning the candle on both ends. But while blaming being tired on a too-hectic lifestyle is commonplace, there is a difference between feeling sleepy and being continuously exhausted.

Maintaining a consistent sleeping routine is essential for your well-being and for bringing about all aspects of a healthy life. Your sleep cycle can make or break your life, which is why it can be frustrating when the pattern is off.

If you are one of the many people who find it challenging to wake up in the morning and then spend the rest of the day feeling exhausted, you may also find it impossible to shut down and sleep soundly in the evening.

How do you fix this seemingly endless, unhealthy and unhappy cycle? Here are some possible reasons for your exhaustion and ways for you to get your energy right.

Reasons for Exhaustion

There are a variety of reasons why you may be suffering from exhaustion, and the causes are going to be varied for every person. However, here are six common reasons.

- A crazy work schedule

Certain work schedules severely disrupt sleep cycles. If you work in a bar, or have overnight or rotating shifts, then there is a high chance your sleeping routine is non-existent. However, working long days or being severely stressed can also disrupt your ability to shut off at night.

- Lifestyle hours that disturb your sleep cycle

If you are a new parent or are overseeing a busy social life, then you probably don't have a set "going to bed" time. Burning the midnight oil over the weekend and then sleeping in will lead to a struggle to fall asleep on a Sunday night, which then directs you to a sleep-deprived Monday morning.

- Constant travel

Traveling is exhausting and is a sure way to say "bye" to any semblance of a routine. Jet lag can wreak havoc on your body and can cause tiredness for a long time after the flight has touched the ground.

- Medical reasons/illnesses

There are several medical-related reasons that you may be suffering from constant exhaustion. Problems such as anemia, thyroid disease, diabetes, depression, and sleep apnea all affect someone's ability to sleep.

- Stimulants like drugs, alcohol, coffee, etc.

Consuming too many stimulants or digesting them at the wrong time are guaranteed means to ruin your sleeping schedule. Don't drink coffee six hours before bedtime, and stop sipping alcohol three to four hours before you try to snooze.

The truth is that you are going to have to be honest with yourself about your lifestyle and the causes of your exhaustion. Only you know how you spend your days, what you consume, and the lifestyle you are living. Being honest with yourself is the first step to tackling the problem.

Fixes for Exhaustion

- Exercise

While you may think that exercising is the last thing you want to do when you are exhausted, it actually is a beneficial way to maintain a sleep schedule and will help you to feel less tired in the long run. Even if you only do a daily 30-minute walk, you will have an energy boost, and then will be more likely to be able to fall asleep at night.

- Natural caffeine

A natural caffeine supplement not only battles exhaustion but also gives you improved cognitive functions, helps with blood sugar and weight management, and encourages healthy aging.

- LIfestyle and environmental changes

Stop checking your phone while in bed, cut down on your alcohol consumption, reduce stress, and eat regular meals. Make sure your bedroom is tidy, purchase some soothing candles and pillow sprays, and implement a night-time routine to help you wind down and relax.

How do you deal with exhaustion? What lifestyle changes have helped you get better quality sleep? Let us know your tips and tricks in the comments below.

Waste products discharged from the digestive tract are composed of up to 75% water, food which is digested but not absorbed, indigestible residue, undigested food, epithelial cells, bile, bacteria, secretion from the digestive tract and inorganic bacteria. Normally an adult human excretes 100-200 grams of feces in a day.

Examination of stool is very helpful in the diagnosis of disease of the gastrointestinal tract as listed below.

Detection of parasites

Stool examination is performed for the detection and identification of worms (adult worms, larvae, segments of worms, ova) and protozoa (cyst or trophozoites). See also: Microscopic Examination of Feces

Bacteriologic examination

Stool culture is performed for the evaluation of bacterial infection such as Clostridium difficile, Yersinia, Salmonella, Shigella or Vibrio. Bacterial toxins (such as those released by Clostridium difficile or Clostridium botulinum) can also be identified. See also: Microscopic Examination of Feces

Evaluation of chronic diarrhea

Chronic diarrhea defined as a passage of three or more liquid or loose stools in a day lasting for more than four weeks. Acute diarrhea refers to the passing of three or more liquid or loose stools in a day for less than four weeks. In diarrhea, stool examination is very important part of laboratory investigations. Depending on the nature of the investigation, either a random stool sample or 72- sample or 48-hour sample is collected. A random stool sample is used for the tests of occult blood, pH, fat, white blood cells, microscopy, or culture. A 72- or 48-hour sample is collected and examined for the weight, carbohydrate, fat content, osmolality, or chymotrypsin activity. Causes of chronic and acute diarrhea are listed in Table 988.1 and Figure 988.1 respectively.

Table 988.1 Classification and causes of chronic diarrhea
1. Watery diarrhea
  1. Osmotic
    • Carbohydrate malabsorption
    • Osmotic laxatives
  2. Secretory
    • Bacterial toxins
    • Bile acid malabsorption
    • Laxative abuse
    • Hormonal disorders: VIPoma, carcinoid syndrome, gastrinoma, hyperthyroidism
2. Inflammatory diarrhea
  1. Invasive bacterial and parasitic infections
  2. Inflammatory bowel disease
  3. Pseudomembranous colitis
  4. Infectious diseases
  5. Neoplasia
3. Fatty diarrhea
  • Malabsorption syndromes

Figure 988.1 Classification of causes of acute diarrheaFigure 988.1 Classification and causes of acute diarrhea

Evaluation of dysentery

Differentiate between bacillary dysentery and amebic dysentery is done by the identification of the causative organism in the stool. See also: Microscopic Examination of Feces

Identification of Rotavirus

In infants and young children, Rotavirus is the most common cause of diarrhea. Rotavirus can be identified by the electron microscopic examination of stool. Other techniques, such as latex agglutination, immunofluorescence, or enzyme-linked immunosorbent assay (ELISA) are also used for the detection of Rotavirus in stool.

Chemical examination

Chemical tests can be applied on feces to detect excess fat excretion (malabsorption syndrome), occult blood (in ulcerated lesions of the gastrointestinal tract, especially occult carcinoma of the colon) and presence or absence of urobilinogen (obstructive jaundice). See also: Chemical Examination of Feces

Differentiating infection by invasive bacteria (like Salmonella or Shigella) from that due to toxin-producing bacteria (like Vibrio cholerae or Escherichia coli)

Feces is examined for the presence of white blood cells. Increased numbers of polymorphonuclear neutrophils (identified by methylene blue stain from the presence of granules in their cytoplasm) are seen as shown in Figure 988.2. See also: Causes, symptoms, diagnosis, and treatment of Cholera

Figure 988.2 Preliminary evaluation of acute diarrhea. Examination of feces for white blood cells is helpful in narrowing differential diagnosis in intestinal infections in acute diarrhea
Figure 988.2 Preliminary evaluation of acute diarrhea. Examination of feces for white blood cells is helpful in narrowing differential diagnosis in intestinal infections in acute diarrhea

What is acute leukemia?

It is defined as malignant clonal hematopoietic stem cell disorders characterized by the rapid increase in the number of blast cells in the bone marrow and rapidly progressive fatal course if untreated. Acute leukemia (AL) are primary disorders of the bone marrow, also known as blood cancer.

Classification of acute leukemias

The most widely used classification of acute leukemias is French-American-British (FAB) Co-operative Group classification. The FAB rule for the classification of acute leukemias was originally proposed in 1976. On the basis of the morphology and cytochemistry, they are classified into two major types.

  1. Acute myeloid leukemia (AML)
  2. Acute lymphoblastic leukemia (ALL)

Each type is further subclassified. See table 883.1

Table 883.1 French-American-British (FAB) classification of acute leukemias
Acute myeloid leukemia (AML)
M0: Acute myeloid leukemia, minimally differentiated
M1: Acute myeloid leukemia without maturation
M2: Acute myeloid leukemia, with maturation
M3: Acute promyelocytic leukemia M3v: Hypo- or microgranular promyelocytic leukemia
M4: Acute myelomonocytic leukemia M4Eo: Acute myelomonocytic leukemia with bone marrow eosinophilia
M5: Acute monocytic leukemia
  • M5a: Undifferentiated (monoblastic)
  • M5b: Well-differentiated (promonocytic-monocytic)
M6: Acute erythroleukemia
M7: Acute megakaryocytic leukemia
Acute lymphoblastic leukemia (ALL)
L1: Lymphoblasts with constant, rounded nuclei, and adequate cytoplasm. Nucleoli are not prominent.
L2: More irregular lymphoblast and cytoplasm is available in large quantity. Nucleoli are large and may see one or more nucleoli.
L3: Large cells with moderate amount of deeply basophilic cytoplasm; prominent cytoplasmic vacuoles; regular nuclear membrane; 1-2 prominent nucleoli

In contrast to French-American-British (FAB) classification, World Health Organization (WHO) classification recognizes AML with recurrent cytogenetic abnormalities, AML with multilineage dysplasia, and therapy-related AML as distinct entities.

Patients with clonal, recurrent cytogenetic abnormalities listed in Table 883.2 are considered to have AML irrespective of the percentage of blasts in blood or bone marrow. These patients have characteristic clinical and morphological features and a favorable response to therapy.

Table 883.2 WHO classification of acute myeloid leukemia (AML), 2001
1. Acute myeloid leukemia with recurrent genetic abnormalities
  • AML with t (8; 21) (q22; q22), (AML1/ETO)
  • AML with abnormal bone marrow eosinophils and inv (16) (p13q22) or t (16; 16) (p13; q22), (CBFβ/MYH11)
  • Acute promyelocytic leukemia with t (15;17) (q22; q12), (PML/RARα) and variants
  • AML with 11q23 (MLL) abnormalities
2. Acute myeloid leukemia with multilineage dysplasia
  • Following myelodysplastic syndrome (MDS)
  • Without prior myelodysplastic syndrome
3. AML and MDS, therapy related
  • Alkylating agent related
  • Topoisomerase II inhibitor related
  • Others
4. AML, not otherwise categorized
  • AML, minimally differentiated
  • AML without maturation
  • AML with maturation
  • Acute myelomonocytic leukemia
  • Acute monoblastic and monocytic leukemia
  • Acute erythroid leukemia
  • Acute megakaryoblastic leukemia
  • Acute basophilic leukemia
  • Acute panmyelosis with myelofibrosis
  • Myeloid sarcoma

Difference between Acute Myelocytic Leukemia (AML) and Acute Lymphocytic Leukemia (ALL)

Table 883.3 Difference between AML and ALL
Characteristic Features Acute Myelocytic Leukemia Acute Lymphocytic Leukemia
Origin of cells Myeloid series cells Lymphoid series cells
Characteristics of blast cells Cell is large in size with moderate cytoplasm. Chromatin patterns are fine and lacy. Nucleoli are prominent and are more than two. Cell is small with scanty cytoplasm. Chromatin patterns are dense. Nucleoli are indistinct and are less than two.
Bone marrow Mixed population of blast and myeloid cells. Mainly blast cells and very few  WBCs or RBCs
Sudan black and peroxidase Positive Negative
Auer rods Present Absent
Periodic Acid-Schiff (PAS) Positive in Erythroblast in M6 leukemia Positive (block patterns) in L1 and L2, and negative in L3
Leukocyte Alkaline phosphatase (ALP) Positive (It is used to differentiate CML from the leukemoid reaction) Negative
Chromatin Patterns
Figure 883.1 Different Types of Chromatin Patterns

Sign and symptoms of acute leukemia

  1. Weakness and fatigue
  2. Low-grade fever
  3. Bone pain
  4. Bruising and mild bleeding from gums
  5. It appears suddenly

Diagnosis of acute leukemia

  1. This disease is most common in younger age group and more frequent in the children. Mostly found before the age of 20.
  2. Rapid development of anemia is most common with normocytic and normochromic red cells. You may see some nucleated red cells in the peripheral blood smear.
  3. Leucocytes (WBCs) count is variable. Mostly leucocytes count is less than 100000/μl.
  4. Thrombocytopenia (See also Morphology of Platelets)
    • Petechiae and purpura may be seen in the skin and mucous membranes.

Laboratory findings in acute myelocytic leukemia (AML)

  1. Total leucocyte count (TLC) is variable. It is recorded that in 25% of patient's total leucocyte count is < 5000/μl, 25% of the patient has > 50000/μl and 5% to 10% has total leucocyte count between 5000 to 10000/μl.
  2. Abnormal and immature WBCs are present.
  3. In 50% of cases, the value of uric acid is raised.
  4. In bone marrow examination, > 20% blast cells are present. Promyelocytes are numerous especially in M3 (acute promyelocytic leukemia). See table 883.1
  5. Cytochemical stains, Sudan black, and peroxidase show the positive reaction.
  6. Auer rods can be seen in the cytoplasm of the cells.
  7. Nucleated red blood cells may be seen.
  8. PT, PTT and Thrombin time are elevated.
  9. Thrombocytopenia may be present and may see the platelets count between 30,000 to 100,000/μl.

Laboratory findings in acute lymphocytic leukemia (ALL)

  1. Total leucocyte count is variable from low to very high.
  2. Anemia and thrombocytopenia
  3. Bone marrow:
    It is difficult to find normal RBCs and WBCs.
    Very few WBCs are seen.
    Characteristically there are blast cells.
    Sudan black and peroxidase show the negative reaction.
    Auer rods are absent.

Test value for the layman

Examination of peripheral blood smear and bone marrow is advised:

  1. If the patient has high TLC.
  2. If the patient has Anemia.
  3. If the patient has enlarged lymph nodes.
  4. If the patient has weakness and fever.

Why are these tests performed?

  1. These tests are performed for the diagnosis of bleeding disorders.
  2. APTT is performed to distinguished the functionality of the clotting factors I, II, V, VII, IX, X, XI, and XII.
  3. APTT is used to check the treatment of the patient taking heparin or other medicine for blood thinning.

See: Role of laboratory tests is bleeding disorders

Collection of Sample

Venous blood sample is collected from antecubital fossa in a test tube containing trisodium citrate (3.2%), with the anticoagulant to blood proportion being 1:9. See also: Prothrombin time (PT): Collection of Specimen.

Precautions

  1. Sample handling is very sensitive, false and raised values are obtained if the ratio of blood and anticoagulant is not correct.
  2. Plasma is stable for one hour if kept at 4º C.
  3. Plasma can be preserved for 28 days if frozen.

Principles

Activated Partial Thromboplastin Time (APTT)

Plasma is incubated with an activator (which initiates intrinsic pathway of coagulation by contact activation). Phospholipid (also called as partial thromboplastin) and calcium are then added and clotting time is measured.

Partial Thromboplastin Time (PTT)

It is one stage test. It distinguishes the functionality of the clotting factors I, II, V, VIII, X, XI, and XII. Both Activated Partial Thromboplastin Time (APTT) and Partial Thromboplastin Time (PTT) have the same clinical significance but Activated Partial Thromboplastin Time (APTT) is more reliable as compare to Partial Thromboplastin Time (PTT) due to its sensitivity.

Prothrombin Time (PT)

Tissue thromboplastin and calcium are added to plasma and clotting time is determined. The test determines the overall efficiency of extrinsic and common pathways.

International Sensitivity Index (ISI) and International Normalized Ratio (INR)

International Sensitivity Index (ISI) of a particular tissue thromboplastin is derived (by its manufacturer) by comparing it with a reference thromboplastin of known ISI. For standardization and to obtain comparable results, it is recommended to report PT (in persons on oral anticoagulants) in the form of an International Normalized Ratio (INR).

International Normalized Ratio (INR) is calculated by the following formula.

INR = PT of Patient ISI
          PT of Control

Purpose of INR: The INR is calculated to evaluate the following conditions.

  1. Atrial fibrillation
  2. Thrombophilia
  3. Cardiomyopathy
  4. Prosthesis (Replacement of heart valve)
  5. Venous thromboembolism
  6. Antiphospholipid syndrome

Normal Values

Technique of APTT, PTT, and PT is different in different laboratories therefore normal values varies with the lab to lab. A normal control is always run with the patient's sample. In general, normal values are below.

  • APTT: 30-40 seconds
  • PTT: 60-70 seconds
  • PT: 11-16 seconds
  • INR: 1-1.5
Table 882.1 Required value of INR in various diseases
Disease Required INR Value
Deep vein thrombosis prophylaxis 1.5 to 2.0
Deep vein thrombosis 2.0 to 3.0
Atrial fibrillation 2.0 to 3.0
Orthopedic surgery 2.0 to 3.0
Pulmonary embolism 2.5 to 3.5
Prosthetic valve prophylaxis 3.0 to 4.0

Critical Values

  • APTT: > 70 seconds (Usually it is considered as panic value. If APTT is greater then 100 seconds, spontaneous bleeding may occur.)
  • INR: > 5.0 (In Deep Vein Thrombosis (DVT) patient on warfarin treatment, an expected value of INR is between 2.0 to 3.0.)

Reasons for the high results

  1. Disseminated intravascular coagulopathy (DIC )
  2. Factor XII deficiency
  3. Cirrhosis
  4. Hemophilia A and B
  5. Von Willebrand’s disease
  6. Hypofibrinogenemia
  7. Vitamin K deficiency
  8. Malabsorption
  9. Leukemia
  10. Fibrin breakdown products
  11. All congenital deficiencies of Intrinsic system coagulation factors
  12. Drugs

The significance of APTT, PTT, PT, and INR test for the layman

  • Patients, taking medication for blood thinning or on heparin treatment, are advised for these laboratory investigations.

Why is this test performed?

  1. This hormone test is evaluated in different conditions, such as Adrenal insufficiency, in Acromegaly and Cushing Syndrome.
  2. In Addison's disease, the level of Adrenocorticotropic hormone (ACTH) is noted more than 1000 pg/ml.
  3. In Adrenal carcinoma, Adenoma, and Adrenocortical insufficiency, the level of Adrenocorticotropic hormone (ACTH) decreases.

Collection of Sample

For the estimation of Adrenocorticotropic hormone (ACTH), patient’s plasma is needed. Blood is collected in a chilled plastic test tube containing EDTA or heparin and blood is placed in cold ice-water.

The sample is centrifuged at 4º C, plasma is separated and stored at -20º C immediately within 15 minutes of the blood collection.

See: Uses of anticoagulants for hematological investigations

Note: For the diagnosis of Cushing Syndrome, the blood sample is collected in between 6 PM to 11 PM.

See: Procedures for the collection of blood for hematological investigations

Precautions

  1. Collect the blood sample in a chilled plastic test tube containing EDTA or heparin.
  2. Avoid high carbohydrates diet, take the low-carb diet.
  3. Avoid physical activity for 12 hours before the collection of the blood sample.
  4. Stop medication such as corticosteroids, 48 hours before the collection of blood sample.
  5. An anxious collection of the blood sample may increase the level of Adrenocorticotropic hormone (ACTH).

Normal Values

  • 6 to 8 AM: < 80 pg/ml or < 18 pmol/L (SI units)
    6 to 11 MP: < 50 pg/ml or < 11 pmol/L (SI units)
    or less than 120 pg/ml
  • According to another references:
    8 AM:  < 120 pg/mL
    4 to 8 PM: < 85 pg/mL
    Cord blood: 50 to 570 pg/mL
    Newborn: 10 to 185 pg/mL
Table 881.1 ACTH and Cortisol values in various conditions and  diseases.
Disease ACTH Value Cortisol Value
Cushing syndrome Increased/low Increased
Adrenal cancer Low Raised
Adrenal adenoma Low Raised
Ectopic ACTH (Lung cancer) Raised Raised
ACTH- producing Pituitary tumor Raised Raised
Adrenal gland failure ( Infarction, Haemorrhage) Raised Low
Hypopituitarism Low Low
Congenital adrenal hyperplasia Raised Low
Addison's disease

Reasons for the increased level of ACTH

  1. Cushing syndrome
  2. Addison's disease
  3. Stress
  4. Ectopic ACTH syndrome

Reasons for the decreased level of ACTH

  1. Secondary adrenal insufficiency
  2. Exogenous steroid administration
  3. Hypopituitarism
  4. Adrenal adenoma or carcinoma

The significance of Adrenocorticotropic hormone (ACTH) test for the layman

  1. This test is advised in abnormal metabolism of lipids.
  2. This test is advised to the patients of Diabetes Mellitus (DM).
  3. This test is performed for the diagnosis of Cushing syndrome.
  4. This test is advised if there are truncal obesity and thin extremity.
truncal obesity
Figure 881.1 Example of Truncal Obesity

Why is this test performed?

  1. The test is performed for the diagnosis of prostatic carcinoma by the estimation of total acid phosphatase (TAP) and the prostatic component.
  2. The test is also performed for the examination for the presence of semen in medicolegal cases by a vaginal swab. Due to the high level of acid phosphatase in semen, its presence indicates recent sexual intercourse. Level of ≥50 U/sample is considered as positive evidence of semen.

Collection of Sample

For the test of total acid phosphatase (TAP) and the prostatic acid phosphatase (PAP), morning sample is preferred. About 3 to 5 ml blood is collected in a vacutainer and blood is allowed to clot. Then blood is centrifuged for 10 minutes at 4500 rpm in order to get the clear serum. The test is performed immediately. However, the sample can be preserved for 24 hours if kept at 2-8º C.

See: Procedures for the collection of blood for hematological investigations

Precaution

  1. The sample has very poor stability in the whole blood, therefore serum is separated immediately and the test is performed within an hour.
  2. The sample is unstable for the test of ACP if the pH is more then 7.0.
  3. The sample is unstable for the test of ACP at room temperature (> 37º C).
  4. Hemolyzed serum causes the false-positive result. Increased values can be observed in hemolyzed serum.

Normal Values

  • Total acid phosphatase (TAP)
    2.5 to 3.7 ng /mL
    or < 3.0 mg /L
  • Prostatic acid phosphatase (PAP)
    < 2.5 ng/mL (0 to 0.6 U/L)
  • Other references
    Adult: 0.13 to 0.63 units/L at 37° C or 2.2 to 10.5 units/L (SI units)
    Child: 8.6 to 12.0 units/mL at 30° C
    Newborn:10.4 to 16.4 units /mL at 30°C

Reasons for the increased level

  1. Prostatic carcinoma
  2. Prostatitis
  3. Benign prostatic hyperplasia
  4. Metastatic carcinoma of the prostate
  5. Metastases to the bones

Moderately raised level seen in, other than prostatic carcinoma

  1. Hyperparathyroidism
  2. Niemann-Pick disease
  3. Sickle cell anemia
  4. Prostatitis and Benign prostatic hyperplasia ( BPH )
  5. Any cancer that has given metastasis to the bones.
  6. Urinary retention
  7. Multiple myelomas
  8. Myeloid Leukemia
  9. Paget disease
  10. Liver diseases like cirrhosis
  11. Renal diseases
  12. Thrombocytosis
  13. Gaucher’s disease

The significance of acid phosphatase test in medicolegal cases

Due to the high level of acid phosphatase in semen, its measurement is very important in rape cases. For the collection of a sample from the victim's body, following methods are applied.

  1. Direct aspiration or saline lavage
  2. Vaginal swab is obtained from the victim's vagina, and the sample is placed in 2.5% broth and can preserve at 4° C.

The significance of acid phosphatase test for the layman

  1. The test is performed for the diagnosis of prostatic carcinoma.
  2. This is carried out in cases of alleged rape or sexual assault.

Purpose of the test

The test is performed to assess the adrenal cortex function, and evaluate and monitor the adrenal tumors and hyperplasia.

How to collect the urine sample for the 17-ketosteroids test?

  1. For the test of 17-ketosteroids in urine, 24 hours urine sample is required. Urine is collected in a container, containing one gram boric acid or 6 ml hydrochloric acid (HCl).
  2. The first urine sample is discarded and then collected the all urine sample for 24 hours.
  3. The 24 hours urine sample is transferred to the pathology laboratory for laboratory findings.

Why is boric acid used for the collection of the urine sample?

Boric acid converts the urine into a bacteriostatic medium, which inhibits the growth of bacteria in urine and preserves the urine for its bacteriological examination.

Precautions

Some medicines like aspirin, diuretics, antibiotics, birth control medication and hormones therapy (e.g. Estrogen) may interfere with laboratory findings, so avoid such types of medicine before preparing yourself for the laboratory test.

Normal Values

  • Males: 8-20 mg/24-hour
  • Females: 6-15 mg/24-hour
  • Elderly males > 70 years: 3-12 mg/24-hour
  • Elderly females > 70 years: 3-13 mg/24-hour
  • Infants: < 1 mg/24-hour
  • 1 to 5 years: < 5 mg/24-hour

Reasons for the increased level of 17-ketosteroids in the 24-hour urine sample

  • Pregnancy
  • Stein-Leventhal syndrome
  • Hyperpituitarism
  • Ectopic ACTH-secreting tumors
  • Administration of ACTH
  • Cushing’s syndrome
  • Congenital adrenal hyperplasia 
  • Testosterone secreting or androgen-secreting tumors of:
    (1) Ectopic ACTH-secreting tumors
    (2) Ovaries
    (3) Testes

Reasons for the decreased level of 17-ketosteroids in the 24-hour urine sample

  • Hypopituitarism
  • Severe infections 
  • Klinefelter's syndrome
  • Addison’s disease
  • Severe stress
  • Nephrosis
  • Debilitating diseases
  • Chronic diseases
  • Castration
  • Myxedema
  • Drugs that can decrease the level of 17-ketosteroids include:
    (a) Probenecid
    (b) Estrogens
    (c) Reserpine
    (d) Thiazide diuretics
    (e) Salicylates (prolonged use)
    (f) Birth control pills

The significance of 17-ketosteroids for the layman

  1. The test is advised if the females has hairs on her face.
  2. The test is performed to elaborate any abnormality or disorders of the adrenal gland.

Anal sex refers to the activity in which penis is inserted into the anus. Some people found anal sex more joyful, but the fact is that the practice has the downside and it contains so many health risks.

It is prohibited in various cultures especially with regard to religious prohibition. It is a criminal offense in some countries and punishable by corporal or capital punishments. By disparity, people regard it a valid and natural form of sexual activity.

Is Anal Sex Safe?

There are so many health risks associated with the anal sex and anal intercourse, for both partners. Some of the health risks which may affect both homosexual and heterosexual couples are listed below.

Risk of bacterial infection: E. coli is a Gram-negative, facultative anaerobic bacteria, that is commonly found in the lower intestine. Anal sex increases the risk of transmission of E. coli bacteria from anal to your penis, which may cause a severe type of urinary tract infection.

E. coli may cause many bacterial infections, including, urinary tract infection (UTI), meningitis, cholecystitis, cholangitis, bacteremia, and pneumonia.

Hepatitis A Virus (HAV): Hepatitis A Virus can transmit by the oral sex (anal licking). HAV causes jaundice. It is usually not a life-threatening virus but may cause illness.

Hepatitis C Virus (HCV): It may be transmitted through the anal intercourse. Hepatitis C Virus is the cause of fetal liver chronic disease. It is a life-threatening virus and may lead to death.

Human Papilloma Virus (HPV): It may be transmitted through the anal intercourse and may cause to the anal wart. A research showed that some of the strain of HPV have carcinogenic potential. Some strains of HPV cause cancer of the cervix in women and also cause cancer of the throat.

Human immunodeficiency virus (HIV): There is a greater risk of transmission of HIV through anal intercourse. It is a life-threatening virus and leads to death.

Weakening of the anal sphincter: The anal anus is enclosed by the ring-like muscle, called the anal sphincter. The main function of anal sphincter is to hold the feces until you get to the toilet. After the excretion of feces, it tightens. Penetration of something like a penis inside the anal can be difficult and painful. Anal intercourse may lead to the weakening of the sphincter muscles, and make it hard to hold the feces.

Lack of natural lubrication: Naturally, the anal is not made for sex. The anal has lack of lubricant as vagina have, which makes the penetration harder and painful. Penetration can tear the tissues inside the anal and cause the wound, allowing viruses and bacteria to easily enter the bloodstream. Somehow, usage of oil or other lubricants can help in preventing the tearing of tissues inside the anal but doesn't completely.

A research showed that risk of transmission of HIV and HPV is much higher in anal sex and compared to the vaginal sex.

How to Prevent Anal Sex Problems

There is no way to completely eliminate the risk factors of anal sex until you avoid the anal sex. However, you can reduce the risk by the following tips.

  1. Always use a condom during anal sex.
  2. Do not enter penis into the mouth after inserting it into the anal.
  3. Use a sufficient amount of lubricants when penetrating into the anal to reduce the risk of tissue tear. Always use water-based lubricants with condoms.
  4. Do not lick the anal as it may cause the transmission of bacteria and viruses.
  5. Take a warm bath before anal sex.
  6. Lying on your stomach will make the insertion easier.
  7. Stop if you feel so much pain during anal sex.
  8. Stop if you experience bleeding or discharge coming from it, go to the hospital as soon as possible.
The Middle East respiratory syndrome (MERS) caused by coronavirus which has a large family of virus. This viral disease first identified in September 2012 in Saudi Arabia. This virus can cause disease ranging from common cold to Severe Acute Respiratory Disease (SARS).
 
This deadly virus may originate from bats and categorize as a zoonotic virus. Which mean a virus that transmitted from animal to human by direct or indirect contact. Especially dromedary camel which is a reservoir host for this virus.
 
Which Country Infected By MERS-CoV
 
Saudi Arabia is the leading country. About 80% of cases have reported. The United Arab Emirates and the Republic of Korea come in second. But specific antibodies that can found in previously infected animal have been identified in Middle East, Africa, and South Asia
 
*According to WHO, since 2012, 27 countries have reported cases of MERS including Algeria, Austria, Bahrain, China, Egypt, France, Germany, Greece, Islamic Republic of Iran, Italy, Jordan, Kuwait, Lebanon, Malaysia, the Netherlands, Oman, Philippines, Qatar, Republic of Korea, Kingdom of Saudi Arabia, Thailand, Tunisia, Turkey, United Arab Emirates, United Kingdom, United State, and Yemen.
 
How MERS-Cov virus Spread or Transmitted?
 
From animal to human. Taking care of infected animal without proper precaution can transmit the virus easily. Eating raw meat or milk without proper preparation can also infect the human.
 
Secondly, they spread by human to close human contact. For example, unprotected care to a patient in health-care facilities. The facilities provided inadequate prevention and didn’t separate MERS patient with another patient. Traveller whose have infected. Traveling to another country and spread the virus.
 
However, the exact route is still unknown.
 
What Are The Symptoms of MERS-CoV
 
Typical symptoms that infected patient presented are the common cold, cough, and shortness of breath. These are the common/mild symptoms. Pneumonia(not always present), and severe acute respiratory disease which leads to respiratory failure. The patient needs to use mechanical ventilation in intensive care unit (ICU).
 
Gastrointestinal symptoms also present for example diarrhea. Some of the patients might be asymptomatic meaning absent from clinical symptoms. But they are positive for MERS proved by a laboratory test.
 
Is There A Possibility For Me To Get Infected?
 
High-risk people: eating raw contaminated milk and meat. Older people. Low immunity person. Chronic disease patient such as renal disease, cancer, lung disease and diabetes. This person should avoid direct contact with camel, drinking raw camel milk or urine and eating raw meat.
 
*According to WHO, 750 death related to MERS-Cov since 2012. But there are still patient with mild cases that might miss due to ignorance about the disease. This disease has high mortality rates of 35%.
 
How Can We Treat MERS-CoV Disease?
 
Unfortunately, there is no vaccine,or specific treatment is currently available. However, according to WHO, three vaccines currently under development. One vaccine to prevent transmission from animal to human. While the other two for outbreaks of this disease and protection for high-risk people). As for now, we can only treat clinical symptoms and supportive treatment.
 
What Can We Do To Avoid The Virus?
 
We can take some precaution. For examples in the farms, market, and barns. The home where dromedary camel and other animals live; we should practice general hygiene measures. Washing hand before and after contact with the animal and avoid visiting sick animal. In health-care facilities, the worker should know or educated in the prevention of disease and applied it. Fortunately, according to WHO, a disease outbreak in healthcare facilities have significant drop compared to previous year.
 
MERS-CoV is still a threatening virus, and WHO reports the recent case. A male patient 74 years old lives in Batinah, Omani. The disease transmitted when he is taking care of his sick camel. Laboratory confirmed that it is a case of MERS-Cov disease. Take care of ourselves better. Educate yourself and take alert of what happens in our world. The world is getting sicker day by day, and we can change it. Little by little.
What Is Yellow Fever? 
 
Yellow fever refers to jaundice that presents in a patient infected with the virus by getting a bite from a mosquito carrying the virus. The virus is arbovirus of the flavivirus genus. And the species of the mosquito is Aedes and Hemogogus. 
 
The disease endemic in tropical areas of Africa, Central, and South America especially Brazil. Circulate in the highest concentrated population with a high density of mosquito. An area that yellow fever vaccination not previously recommended. 
 
*According to WHO, between 1 July 2017 and 28 February 2018, 723 confirmed human cases of yellow fever had reported in Brazil, including 237 deaths. This number increase since 2015/2016. 
 
What Are The Symptoms Of Yellow Fever? 
 
Symptoms include fever, headache, jaundice, muscle pain with prominent back pain, loss of appetite, nausea, vomiting, and fatigue. Most cases are asymptomatic for few days after bitten by a mosquito. Some symptoms disappear after 3 to 4 days. 
 
Severe symptoms or toxic phase just within 24 hours after initial symptoms disappear may occur. By high fever and affected several systems such as liver and kidney. The patient will develop jaundice, dark urine and abdominal pain with vomiting. Bleeding can occur from patient’s mouth, nose, ear or stomach. Within 7 – 10 days, half of the patient may die. 
 
Misleadingly yellow fever symptoms can be confused with severe malaria, leptospirosis, viral hepatitis, other hemorrhagic diseases, and poisoning. But testing Polymerase chain reaction (PCR) in blood and urine can help detect the disease in early stage
 
Do I Have Possibility Getting Yellow Fever? 
 
High-risk people are people who live in an endemic area in Africa and Central South America. Travelers who visit the yellow fever area may spread the disease in another country. Old people over 60 years old or patients with severe immunodeficiency can easily get infected. 
 
How Can Yellow Fever Transmit? 
 
Three ways can transmit the disease. First, a worker who’s working in the jungle or brave traveler roaming in the forest is bitten by a mosquito. The mosquito transfer the virus in monkeys which is a reservoir host for the virus by biting them. 
 
The second way is the mosquito infected both monkey and human. The mosquito roaming in the jungle and household. Increase contact from both of species will lead to outbreaks even in neighborhood village at the same time. In Africa, the second way is the most common way to cause an outbreak of yellow fever disease. 
 
The third way is when infected people bring the disease in an area with high density of mosquito and lack of vaccination. Plus this people usually have low immunity and easily to be infected. In this case, the disease transmitted from people to people. 
 
Do We Have Treatment For Yellow Fever? 
 
Treatment is supportive treatment from the hospital. The specific drug for yellow fever is still under development. Treating the symptoms present such as liver or kidney failure and fever may improve the outcomes. 
 
However! 
 
We can prevent it! 
 
By highly effective vaccine which is safe and affordable. A single dose is sufficient to prevent the disease and prolong the lifespan. Plus a booster dose is not needed. Within 30 days the vaccine provided effective immunity for the person vaccinated. 
 
Prevention by vaccination is the most important step in battling against this disease. At least 80% of the population in an endemic area should be vaccinated to prevent the outbreak. Don’t forget the traveler who is going to visit the endemic area need to confirm whether they are vaccinated or not. Many countries require the traveler to prove that they have been vaccinated for yellow fever before issue visa, especially in endemic countries. 
 
But! 
 
Some people excluded from vaccination. Please pay attention to this to avoid other problems.
 
  • Infants aged less than nine months. But if the infants live in the endemic area, they are required to be vaccinated.
  • Pregnant woman except during outbreak of disease.
  • People with severe allergies to egg protein.
  • People with low immunity due to HIV/AIDs and thymus disorder
 
Other prevention is mosquito control. Eliminate potential breeding sites by applying larvicides to prevent breeding of mosquito larva. We can put the larvicides in water container or places where water is collected.
 
Doing surveillance on Aedes or Hemogogus species by knowing which area have a high density of them can prevent further outbreak. We can apply vector control as early as possible. We also can prevent it by minimizing exposure of ourselves to avoid mosquito bite.
 
The Eliminate Yellow fever Epidemics (EYE) Strategy launched in 2017. An initiative to prevent, detect and respond to suspected case and outbreaks. With an objective to protect, prevent and contain outbreak as soon as possible. Many strategies have implied such as promoting vaccination, increase surveillance on mosquito and expanding partnership with different countries. Hopefully by 2026 more than 1 billion people will be protected against the disease.

The medical term for an infection in the vagina is vaginitis. The infection caused by any pathogenic organism such as streptococcus, staphylococcus, Trichomonasvaginalis or maybe Candida. It can happen in a child of age one to five years old, adults and old women.

But How Do You Get Infected?

The organism can transmit from a child or adult by hands or clothes. Sometimes a foreign body such as a pin is inserted by the child into the vagina can cause infection. Wiping your butt from your anus to vagina may transfer organism to the vagina.

A child with a near infection or tonsillitis can transmit bacteria by hand to her genital area as she is touching it.

Sexual abuse is leading to any sexually transmitted disease as gonorrhea.

Or nylon underclothes and harsh soap may cause the infection in your vagina.

So What Are The Symptoms Of Vagina Infection?

  1. Vaginal discharge. Purulent (pus discharge), blood stained if there is a foreign body or cervical polyp (growth that appear on the cervix look like bulbs on thin stems).
  2. Irritation, pain, and soreness due to discharge.
  3. Severe itching of the skin area around genital.
  4. Pain during peeing like burning sensation and the frequency of peeing is an increase.

How Does Your Genital Look Like If Infected?

The vulva is inflamed, red, tender, sometimes oedematous and bathed in discharge. The labia minora might stick together but can be separated apart leaving inflamed red surfaces.

What Treatment Will You Get?

You need to get proper treatment in the hospital to avoid further infection.

A specific antibiotic is given according to the nature of the organism. For non-specific vaginitis, estrogen cream is applied to the vulva each night for about two weeks. It increases local resistance to infection and relieves soreness.

Any foreign body must be removed. Local washes with warm water and boiling of the underclothes which should be cotton. If one of your child infected, you must isolate from other children to prevent cross infection.

Take extra precaution in sexual activity to avoid sexually transmitted disease which can cause infection to your vagina.

Monitor your daughter during her play time or any changes happen to her. Since prevention is better than cure isn’t it?.

Reviewed by Dr. Nida Hayat Khan
Editor @ BioScience.pk

Menopause is a phase when you stop getting your period. It marks the end of your menstrual cycles. You stop getting your period for at least six months or one year and confirm with your gynecologist. Woman between 40s to 50s is the age of getting menopause, but in the United States, the average age is 51 years old.

Which Types of Menopause You Could Get?

  1. Normal or Natural menopause: occurring between the age of 40 and 55 with an average of 50 years
  2. Premature menopause: Period stop before you hit 40. About 1% of women have menopause below the age of 40
  3. Delayed menopause: you still have your period until the age of 55
  4. Artificial menopause: caused by surgical removal of both ovaries or destruction of ovaries by exposure to irradiation

How Menopause Started?

Maybe preceded by the infrequent period, scanty or decrease the amount of your usual period (less than 30ml). Or the length of your period becomes less to two days. A period of dysfunctional uterine bleeding or suddenly your period stop and never return. About 10% of women suddenly their period stop.

What Changes Happen To You During Menopause?

General Changes:

  1. Your breast might become smaller due to tissue in your breast atrophied or larger due to increase fat deposition
  2. Your appetite may be decreased or increase which leading to obesity. Constipation and gases accumulate (Fart! Fart! Fart!)
  3. The tendency to develop menstrual hypertension as the amount of estrogen decrease. Oestrogen can protect you from atherosclerosis
  4. You gradually have a high risk of coronary heart disease because the level of cholesterol and triglycerides is increased
  5. Liability to osteoporosis (bone disease which resulted in bone become weak easy to break)
  6. Mild hirsutism (increase amount of hair in the manly pattern, e.g., in an area where men typically grow hair)
  7. Psychological changes for examples headaches, irritability and depression

Local Changes:

  1. The pubic hair becomes scanty, grey or white
  2. The vagina becomes narrow, and the pH becomes neutral or alkaline. This condition will predispose to infection
  3. The uterus becomes small and atrophic. Senile endometritis may occur (inflammation of uterus)
  4. The ovaries become small, fibrotic (excess fibrous of connective tissue) and containing no follicles (no egg)
  5. Bladder becomes small. The condition may lead to going to the bathroom a lot (you pee a lot), inflammation of your bladder and urethra

Symptoms You Might Get With Menopause

Palpitation, hot flushes (sensation of heat felt in the chest, neck, face, head or spread to all over body) and night sweats. About 75% of postmenopausal women have hot flushes. Usually, hot flushes disappear after one or two years even without treatment from a doctor.

The hot flush lasts for seconds, minutes, and rarely for one hour but usually 3 minutes. One or two in 24 hours to one every 15-30 minutes in a day.

However, about 25% of cases will continue to have hot flushes for more than five years.

Lack of concentration, poor memory and insomnia (difficult in sleeping/staying asleep). Insomnia is usually the result of night sweats

Joint pain and backache due to loose ligament and muscle become weak

What Can You Do With Menopause?

Well, menopause is a change in life and not the end of life. You can avoid factors which can cause hot flushes as hot weather, hot bath, nervousness, excessive intake of coffee or tea, excessive blanket and covering during sleep.

Control of diet with less fat to avoid obesity. Increase intake of calcium, i.e., dairy product, green leafy vegetables, nuts or fish where you eat the bones-sardine and pilchards.

However!

There are some treatment or therapy to help you in menopause.

Treatment for symptoms such as depression and palpitation

Estrogen therapy: for a woman without a uterus

Given to women if the symptoms such as hot flushes, senile vaginitis (inflammation of vagina), increase the frequency of peeing and psychological disturbances. Treatment is given for at least one year to prevent recurrence of symptoms

This therapy also is given to premature menopause as this condition predisposes to osteoporosis (bone break easily). Treatment is given at least until the age of 50 years. The treatment reduces the risk of osteoporosis by 50% to 60%

Combined estrogen-progesterone therapy: for a woman with a uterus

To protect against endometrial hyperplasia (womb cancer).

Progesterone alone is given to control hot flushes. Although progesterone less effective than estrogen but it causes a less side effect.

Menopause happens to every woman on earth. It differs in every woman of how it started, the changes in your body, the symptom might present in you and the suitable treatment you can do. Consult your gynecologist for explanation and reassurance of the changes in your life.

Medically reviewed by Dr. Nida Hayat Khan
Editor @ BioScience.pk

Have you ever listened about the “Second Brain”?
 
Yes, you have! whenever you are told to trust your gut instinct. This brain and gut connection is not just metaphorical. An extraordinarily extensive network of neurons (more than 100 million neurons) lines our gut that scientists have named it the Second Brain.
 
What about the inhabitants of gut including good and bad microbial flora?
 
Gut microbiota weighs up to 2kg containing trillions of micro-organisms. One-third of these microbiotas is common to all people while others are specific to every individual’s gut depending on the type of diet they take in and their lifestyle.
 
“Gut flora is a complex community of organisms that inhabit human and animal digestive system”. Relation between humans and gut flora is mutualistic. Bacteria in the digestive system assist in nutrient metabolism, vitamin production, and waste processing. They also aid in the host's immune system response to pathogenic bacteria.
 
Healthy Microbiota & Healthy Brain
 
The gut has a bidirectional relationship with the central nervous system referred to as the “gut-brain axis”. Introduction of good bacterial strain reduces anxiety and stress level. Gut-brain axis is used by bacteria to affect the brain function. The most significant factor related to the health of microbiome -- thus, brain – is healthy food. Following are the positive influencing microbiota Lactobacillus that produce lactic acid are found in yogurt. Taking in yogurt will boost mental capacity and relieve stress, it also aids in digestion and relieves constipation. But make sure yogurt is live culture (probiotic). Bifidobacteria feast on chocolate and ferment it causing positive effects on our health and body. Dark chocolate is also very beneficial for the heart because bacteria (Bifidobacterium, LAB, yeast) ferment it into healthful anti-oxidants. Prebiotic foods including raw garlic, raw, and cooked onions allow the healthy microbiota to grow and thrive while inhibits the growth of non-healthy microbiota. Environmental toxins can disturb microbiome and have adverse effects on brain health to save ourselves from these effects, use of home filtered water should be made compulsory. Such filters should be used that remove harmful toxins like chlorine. Fermented foods like pickles, kefir, kimchi etc. are the source of Lactobacillus lactis species and defend against leaky gut. These were some healthy microbial flora and their sources having a positive effect on your body and brain.
 
Non-Healthy Microbiota & Whacky Gut
 
There are bidirectional links between stress and microbiota. Irritable Bowel Syndrome (IBS) and Chronic Fatigue Syndrome (CSF) are also related to the gut microbiota. In CSF patients there is an alteration in normal microbiota resulting in symptoms as depression, neurocognitive impairment, pain and sleep disturbance. While IBS is considered as a gut-brain disorder which is worsened by stress. Researchers are investigating whether these unhealthy microbiota resulting in IBS are also the cause of mood disorders. No bacteria can be inherited as bad, when our body is out of balance it takes advantage and proliferates. Some bacteria having a bad reputation are given below Microbial imbalance as a high level of Lactobacillus can also cause mood disturbance and sleep disturbances. Staphylococcus can cause food poisoning, it can be found in unpasteurized milk and can affect when hygiene is poor. Higher levels of the bad clostridium bacteria can cause fatigue by using bidirectional gut-brain axis. By eating junk food firmicutes and bifidobacteria level falls and there is a rise in the level of bacteroidetes causing the lethargic behavior to upshot and immunity problems set in.
 
Healthy Gut of a Baby
 
It is believed that when babies are born their guts are sterile, as soon as they encounter the genitourinary tract and mother’s skin, they are exposed to microbial flora. Microbial flora is important to develop in infants or babies for normal functioning. This healthy microbial flora to a baby is also provided by mother through breastfeeding. Milk is a cocktail of healthy microbiota and immunoglobulins causing development and growth of microbial flora in infant’s gut. So it is necessary for mothers to take healthy balanced diets rich in probiotic, prebiotic and fermented foods.

Due to the increased demand for fruits and vegetables, portals like Selly.pk offer a much feasible way of shopping. It takes a lot less effort to buy fruits and vegetables online.

Selly.pk is a welcome initiative if you ask me because the streets and roads are already piling up with fruit & vegetable vendors. More people should realize similar ideas. However, this can be depressing for those conventional vendors if the people start buying online sabzi in Lahore. The status quo always works against change but because this is a good change, we should all work together to make it a successful prospect.

Selly.pk Doing Business with Morals

Fruit market Lahore receives new rates of fruits & veggies daily. In order to comply with a standardized rate, Selly.pk is in touch with fruit officials who know this industry on fingertips. This only gives it an upper hand over the common vendors who are more interested in earning high profits rather than being civil and selling products at a decent price.

In the fruit & vegetable market, the Jin of inflation is still under control but as soon as those items reach private vendors in different localities, the price starts touching the skies. Fruit price in Pakistan should have checks & balances so the vendors can’t get greedy.

Your Online Partner

Selly.pk is one of a kind online fruit shop in Lahore. There are not many online fruit shops in Pakistan, therefore, this is a healthy and productive initiative. Where to order fresh vegetables online? How many of us haven’t thought about this question? It is time, a serious response came through and it has in the form of Selly.pk.

Price Comparable to the Average Market Price

It is a pioneering name regarding online fruit and vegetable shopping. Moreover, one would think the price would be higher because it is online. No, not at all. I do most of my shopping from Selly.pk and the online vegetable rates are lower than most vendors out there.

Every household has a need for a fresh supply of fruits and vegetables daily. Online vegetable shopping is much more time-saving because lives are getting busier every day. It is not easy to stop the car on your way back home from work and buy fruits or vegetables.

Fixed Reasonable Rates – Bargaining Not Required

There is no need to overexert yourself anymore with Selly.pk in town. Online vegetable shopping is simpler rather than spending your brains in bargaining with the vendor at the end of the street. Moreover, the call representatives taking your call are very well-behaved, often stating the list of items to make the selection process easier for you. As soon as you place an order for fresh vegetables online, the processing starts and they promise you to reach within 45 minutes. In my case, they have always been on time. They have met my expectations so far delivering high-quality fruits and vegetables to my doorstep.

Buying Fresh Fruits and Vegetables Online Through Selly.pk

Call at your Convenience

Some of us may have trouble ordering through the website due to the fact some of us aren’t technical enough. But you can always call on 0304-111-7355 to place your order.

How Can We Pay?

Cash on delivery is encouraged because we can’t pay by debit or credit cards on the website. Neither is there a card reader with the rider to swipe those cards. These two procedures are something that is lacking in the current order of things.

The riders delivering the goods speak to you in a polite tone without being aggressive or suddenly getting rude.

Return Policy

They have openly declared their return policy. We can instantly return stale fruits or vegetables at the time of delivery and no questions, whatsoever, will be asked.

Fruit and vegetable grocery list – it doesn’t matter how long the list is, Selly.pk is always up for the task delivering them on time. Fresh fruit for sale online, especially in winters is more like a blessing because it’s too cold to go out for shopping anyway. Buy vegetables online easily through Selly.pk because the website is superb. Just keep on tapping the items you want to buy and keep adding them to cart until you are ready to check out.

Elite Packaging

Fresh vegetables for sale at this website are packed in a luxurious way, unlike those cheap plastic bags we normally see at shops, with a symbol or monogram of Selly.pk attached to each packet.

The Gist of the Matter

Selly.pk provides fresh vegetables near you if you are in Lahore. However, one can consider it as a fresh vegetable market nearby with so many choices to choose from. You only need a working smartphone with an active Wi-Fi connection or mobile data connection. Type in Selly.pk in your browser and you are good to go. Fresh fruits and vegetables delivered to your doorstep in a matter of minutes. Shopping was never so convenient before!

TORSION
 
Torsion is a process in which the viscero-pallium rotates anti-clockwise through 180° from its initial position during larval development. So that the mantle cavity, with its pallial complex, is brought to the front of the body in the adult.
 
How Torsion Occurs
 
Torsion is not an evolutionary hypothesis. Its occurrence can be seen during embryogeny of living gastropods. Before torsion the larva is quite symmetrical, the mantle cavity is backward and downward, the alimentary canal is straight and anus opens posteriorly in the middle line. The shell and visceral mass originally saucer-shaped, which is first cone-shaped and then spirally coiled. When the shell lies dorsally and forms a coil anterior side then the shell is called exogastric.
 
The ventral flexure is followed by a lateral torsion, so that the dorsal or exogastric shell becomes a ventral or endogastric shell. The entire process takes 2 to 3 minutes as in Acmaea.
 
Torsion is actually effected due to the contraction of the larval retractor muscles, in which only the narrow neck of the larva is actually twisted. So the everything between the head and the anus undergoes an anti-clockwise rotation at the angle of 180°.
 
Thomson (1958) described five ways by which the torsion can be brought about.
 
  1. In Archaeogastropods, the Acmaea, the torsion takes place by muscles contraction alone.
  2. The rotation of 180° is completed in two stages, the first movement takes place by the contraction of larval retractor muscle and second rotation is slower by different growth. It is very common as in Patella, Haliotis etc.
  3. The rotation of 180° takes place by only differential growth processes like Vivapara.
  4. Rotation by differential growth processes, with anus coming to a position appropriate to the adult state like Aplysia.
  5. Torsion is no longer recognizable as a movement of viscera-pallium, the organs in the post-torsional position from their first appearance as in Adalaria.
 
Effects of Torsion
 
The effect of torsion first time indicated by Spengel in 1881. The effects are not equally examined in all the gastropods by the general effects are described as follows:
 
  1. Displacement of mantle cavity: The mantle cavity was primarily present on the posterior side. The elongation of the ventral foot which was primarily very small. After torsion, the mantle cavity opens just behind the head and its associated parts are shifted forwards.
  2. Changes in relative position: Before torsion, the anus, ctenidia and excretory opening were placed on the posterior side and the auricles were placed behind the ventricle but after torsion the anus, ctenidia and excretory opening become anterior and the auricles lie in front of the ventricle. The original posterior face of the visceral sac becomes the anterior face so that the visceral organs morphologically of the original right side change into the left side.
  3. Looping of alimentary canal: The alimentary canal which was originally straight from mouth to anus, after torsion, it changes into a loop.
  4. Chiastoneury: The long, uncoiled pleuro-visceral nerve connectives become a figure of "8" after twisting. The right connective with its ganglion passes over the intestine to form the supra-intestinal connective, while the next connective pass under the intestine to form the infra-intestinal connective.
  5. Endogastric coil: The coil of visceral sac and shell, which was primarily dorsal or exogastric become ventral and endogastric after torsion.
  6. Loss of Symmetry of Atrophy: The anus changes their original position towards the right side of the pallial cavity so that the original symmetrical condition disturbed.
 
DETORSION
 
The torsion is reversible in Eu-thy-neura and its reversal is known as detorsion by which animal become untwisted and symmetrical.
The “pearl” is literally formed by the mantle epithelium, which becomes deposit around any external body or particles, these external particle or body invade in between the shell and mantle in any way.

Pearl is secreted by the mantle as a means of protection against a small external particle. When an external particle or body, such as a grain of sand or a small parasite invades in between the mantle and the shell it becomes enclosed in a sac of mantle epithelium which produces irritation. The irritation stimulates the mantle epithelium to secrete thin concentric layers of mother of pearl around the foreign body. The amount of deposition is in direct proportion to the degree of irritation. After several years, a pearl will be formed, usually, it requires 3 to 4 years to produce a pearl of considerable size but a large pearl requires about 7 years. The foreign particles in the pearl are called nucleus whereas the thin nacre layers are concentric and called the mother of pearl.
 
Pearls are formed by various clams and oysters, but those produced by the marine pearl oysters, Meleagrina of Eastern Asia are the most valuable.
 
Formation of Pearl
 
 
Blackheads are the most common problem in the majority of people. This problem arises when the oily secretion of the sebaceous glands forms a blockage in your skin pores. When the oil is exposed to air, it oxidizes and turns into black and forms blackhead. So the question is that how you can remove blackheads from your skin.
 
Removing of blackheads from your skin is very simple and you can do this at home, all you need to do is remove the entire blockage from your skin pores.
 
In order to remove the blockage from your skin pores, you need the following material.
 
  1. Towel or soft cloth
  2. Blackhead removal strips or pads
  3. Salicylic acid (C7H6O3)
 
Step 1
 
Wash your skin with the slightly hot water, and gently compress your skin pores with the help of towel or soft cloth. The warmth will open the pores of your skin and make it easier to remove the blockage caused by secretion of the sebaceous glands and to get rid of blackheads. Follow this step upto 5 times.
 
Step 2
 
Apply a blackhead elimination strip or pad to your face while your skin pores are still moist from the compress done in step 1. The moisture to your pores and skin will help the blackhead removal strip cohere on your skin and blackheads. Allow 10 to 15 minutes for the blackhead removal strip to stick itself.
 
After 10 to 15 minutes, pull the strip off. It should remove the blockage and blackheads from your skin pores in a different level of success. But in some cases, it removes the entire blockage and blackheads; in other situations, only the head of the blockage is ripped from the pores of the skin.
 
Step 3
 
With the help of your fingertips, squeeze your skin gently to remove the blackheads from your skin. Note that fingernails should not be used for that purpose as it may harm your skin. If they do not pop out effortlessly, do not squeeze harder as it may harm your skin. Rather, try making use of warmth compress and squeezing another time straight away after removing the warm compress.
 
If the blackheads do not pop out by this method, they probably cannot be removed adequately with your fingers.
 
Step 4
 
Salicylic acid (C7H6O3) is a medication most commonly used for the skin treatment. It removes the outer layer of the skin and most commonly used for the treatment of calluses, dandruff, acne, ringworm, warts, psoriasis and ichthyosis.
 
Apply a thin layer of salicylic acid liquid or paste onto your skin and leave it for a minute. After the use of salicylic acid, do another hot compress and try to squeeze out the remaining extra blackheads.
 
MODE OF ACTION: When you apply the layer of salicylic acid liquid onto your skin, it breaks down the sebum oil and can get deep into your skin pores where your fingers cannot.
You can compare the deionized water vs distilled water, however, to mention that the distilled water is that the same as deionized water may be a mistake. The terms “distilled water” and “deionized water” are usually misunderstood. during this article, you'll notice the reason to grasp the variations and similarities of those 2 completely different water cleanup technologies.
 
DISTILLED WATER
 
The oldest technique for production of pure water is that the thermal technique or distillation – water evaporation from the surface and condensation. the premise of the method is that the transfer of water within the vapor section with its later condensation. the most downside of this technique is that the terribly high maintenance prices of the electricity required to convert the water into the steam. additionally, within the method of steam formation in conjunction with water molecules, alternative solutes will enter the steam in keeping with their volatility. Evaporation is achieved in varied ways: the vacuum on top of the water, heating, etc.
 
Let’s contemplate the distillation. What’s happening within the method of distillation? The water molecules have the boiling purpose of 100°C or 212° F. alternative substances have completely different boiling points. The substance that boils at a lower temperature evaporates initial. The boiling purpose of assorted impurities is higher, and, in theory, they're going to begin to evaporate, once the water has already cooked out. The substance that boils at a lower temperature evaporates initial. because of this distinction the water is separated.
 
As a result, in theory when the distillation the fully pure water is obtained. Actually, organic substances, that have the similar boiling purpose than that of water will supply the water. let's say if the water contains the oil drops they will be found additionally within the liquid. There area unit much no salts within the water, as a result of the salt boils at a far higher temperature. To eliminate the matter of organic substances, the water distillers have pre- and post water filters.
 
The absolute advantage of the water is that the complete absence of harmful substances.
 
REVERSE OSMOSIS (RO) WATER
 
The latest various to the thermal technique for getting of water may be a two-stage reverse diffusion. The technology relies on the double passage of raw water through a tissue layer beneath the pressure. As a result, water is split into 2 streams: the filtrate (purified water) and concentrate (a targeted resolution of impurities). The two-stage reverse diffusion system will considerably cut back operational prices and improve the standard of obtained water. The reverse diffusion water treatment technology is that the most typically employed in households and within the trade for preparation of drinkable.
 
DEIONIZED (DI) WATER
 
Deionized water is deeply demineralized, ultrapure water with the impedance on the point of eighteen megohm-cm. it's employed in electronics, computer circuit boards, instrument manufacture, pharmacy, laundry liquids, etc.
 
In order to get the top quality pure deionized water, a multi-stage water purification method is used. when pre-cleaning, the water is equipped with the reverse diffusion membrane, so the water is filtered through a special deionization medium, that removes the remainder of the ions from the water. The purity of deionized water will exceed the purity of water.
 
SIMILARITIES AND DIFFERENCES: DISTILLED WATER Vs RO WATER Vs  DEIONIZED WATER 
 
 DISTILLED WATER REVERSE OSMOSIS (RO) WATER DEIONIZED (DI) WATER
Distillation is employed in the main in laboratories and factories, wherever it's required. Reverse diffusion is widely employed in water treatment plants, each reception and for the manufacture of assorted drinks, drinking water, etc.
  • RO water is additional saturated with salts and atomic number 8 then the water and DI water.
  • Reverse osmosis and deionization are more cost-effective than the distillation.
DI water is as pure because the water or maybe purer

 

Distillation, RO and deionization processes are supposed to purify the water of the contaminants: mercury, lead, strontium, nitrates, phosphates, manganese, in addition, pesticides.
 
Diabetes is epidemic; there is barely any family left that does not have a member diagnosed with diabetes. In urban areas, almost one-tenth of people have diabetes, and at least one-third are at risk of developing it soon if they do not do something about it. That means if not diabetic, every family surely has someone with prediabetes.
 
Diabetes is primarily caused by faulty lifestyle, followed for years, wrong kind of diet, absolute lack of exercise, and chronic stress, and low interaction between family members are all contributors to it.
 
Diabetes differs from all the other diseases in a way that it is infectious by lifestyle instead of microbes. Meaning a particular kind of lifestyle seems to prevail within the family. Finding an only single obese person in a family is rare. Similarly, if one is not doing exercise in the family, probably none is doing it.
 
The family is intended to function as a single entity, but not in negative direction, thus by changing the course of lifestyle by motivating and helping each other, whole family can benefit.
 
However, it seems that families are not discussing much diabetes, exercise, stress, and emotional problems.
 
“They say they care, but they rarely help, participate or motivate, they do not seem to understand me” is the most common complaint of people about their family members and close friends. In fact, some research shows that often friends are helping and providing more emotional support than the family members.
 
Although we all expect greater emotional support from family members, lack of such support may have reasons like little time or other lifestyle issues.
 
Can family support indeed make a difference?
 
At least all the research, hundreds of them, seems to support the idea that family support can make a huge difference. As we already mentioned that particular kind of lifestyle is prevalent in the whole family.
 
Whether it is a preference for specific type of food items, going out, meeting friends, doing exercise, spending leisure time, everything needs to be changed in diabetes, and perhaps everyone in the family has to change a bit. Wouldn’t it be best to work as a team? Instead of individual efforts. Sharing experience, motivating, has indeed shown to make efforts more successful.
 
Research has shown that adherence to exercise and medications are much better when done with the family support. Married people usually have higher compliance rate, though that cannot always be said about the lifestyle changes. People with families may exercise less as compared to those living alone.
 
Isn’t a family all about emotional support, love, help? Principally it must be the case, though in reality things often differ.
 
Thus for better diabetes management, prevention, it is vital that the whole family participates, and the process does not have to be boring. Supporting each other should be converted into a game, a fun, something to be enjoyed, something that brings emotional happiness to all the participants.
 
Iron sharpens iron; humans are not made to be left alone. They always psychologically feel better when they are continually communicating, when they are loved and praised. Modern technology has made us busier than ever; we are spending more time in unnecessary communication at the cost of neglecting the necessary one.
 
Thus the solution to the problem created by the technology should also be sought in technological advancement itself.
 
Why not start using an app that is made explicitly for members of the family, instead of social apps that are more open, and less focused on interaction at the family level.
 
An app called CricleCare is explicitly made to fulfill that gap. It is a fun way to keep you close friends and family members motivated. It is different in a way that it has been created to improve the communication between the small and closed circles. It has all the tools to make that conversation more relaxed and fun. So you can exchange messages, send stickers. Most importantly, you can encourage the family members by giving batches. Thus you can provide batches to kids for being good at home, doing all the tasks. Give batches for keeping up with exercise, reminding to take medicine, and much more. It has many features of health app like counting steps, providing information about burnt calories. However, unlike the traditional health apps, it is also about the involvement of the whole family. It merges the benefits of health app and family support platform.
Total serum thyroxine includes both free and protein-bound thyroxine and is usually measured by competitive immunoassay. Normal level in adults is 5.0-12.0 μg/dl.
 
Test for total thyroxine or free thyroxine is usually combined with TSH measurement and together they give the best assessment of thyroid function.
 
Causes of Increased Total T4
 
  1. Hyperthyroidism: Elevation of both T4 and T3 values along with decrease of TSH are indicative of primary hyperthyroidism.
  2. Increased thyroxine-binding globulin: If concentration of TBG increases, free hormone level falls, release of TSH from pituitary is stimulated, and free hormone concentration is restored to normal. Reverse occurs if concentration of binding proteins falls. In either case, level of free hormones remains normal, while concentration of total hormone is altered. Therefore, estimation of only total T4 concentration can cause misinterpretation of results in situations that alter concentration of TBG.
  3. Factitious hyperthyroidism
  4. Pituitary TSH-secreting tumor.
 
Causes of Decreased Total T4
 
  1. Primary hypothyroidism: The combination of decreased T4 and elevated TSH are indicative of primary hypothyroidism.
  2. Secondary or pituitary hypothyroidism
  3. Tertiary or hypothalamic hypothyroidism
  4. Hypoproteinaemia, e.g. nephrotic syndrome
  5. Drugs: oestrogen, danazol
  6. Severe non-thyroidal illness.
 
Free Thyroxine (FT4)
 
FT4 comprises of only a small fraction of total T4, is unbound to proteins, and is the metabolically active form of the hormone. It constitutes about 0.05% of total T4. Normal range is 0.7 to 1.9 ng/dl. Free hormone concentrations (FT4 and FT3) correlate better with metabolic state than total hormone levels (since they are not affected by changes in TBG concentrations).
 
Measurement of FT4 is helpful in those situations in which total T4 level is likely to be altered due to alteration in TBG level (e.g. pregnancy, oral contraceptives, nephrotic syndrome).
 
Total and Free Triiodothyronine (T3)
 
Uses
 
  1. Diagnosis of T3 thyrotoxicosis: Hyperthyroidism with low TSH and elevated T3, and normal T4/FT4 is termed T3 thyrotoxicosis.
  2. Early diagnosis of hyperthyroidism: In early stage of hyperthyroidism, total T4 and free T4 levels are normal, but T3 is elevated.
 
A low T3 level is not useful for diagnosis of hypothyroidism since it is observed in about 25% of normal individuals.
 
For routine assessment of thyroid function, TSH and T4 are measured. T3 is not routinely estimated because normal plasma levels are very low.
 
Normal T3 level is 80-180 ng/dl.
 
Free T3: Measurement of free T3 gives true values in patients with altered serum protein levels (like pregnancy, intake of estrogens or oral contraceptives, and nephrotic syndrome). It represents 0.5% of total T3.
 
Thyrotropin Releasing Hormone (TRH) Stimulation Test
 
Uses
 
  1. Confirmation of diagnosis of secondary hypothyroidism
  2. Evaluation of suspected hypothalamic disease
  3. Suspected hyperthyroidism
 
This test is not much used nowadays due to the availability of sensitive TSH assays.
 
Procedure
 
  • A baseline blood sample is collected for estimation of basal serum TSH level.
  • TRH is injected intravenously (200 or 500 μg) followed by measurement of serum TSH at 20 and 60 minutes.
 
Interpretation
 
  1. Normal response: A rise of TSH > 2 mU/L at 20 minutes, and a small decline at 60 minutes.
  2. Exaggerated response: A further significant rise in already elevated TSH level at 20 minutes followed by a slight decrease at 60 minutes; occurs in primary hypothyroidism.
  3. Flat response: There is no response; occurs in secondary (pituitary) hypothyroidism.
  4. Delayed response: TSH is higher at 60 minutes as compared to its level at 20 minutes; seen in tertiary (hypothalamic) hypothyroidism.
 
Antithyroid Antibodies
 
Box 864.1 Thyroid autoantibodies
 
  • Useful for diagnosis and monitoring of autoimmune thyroid diseases.
  • Antimicrosomal or antithyroid peroxidase antibodies: Hashimoto’s thyroiditis
  • Anti-TSH receptor antibodies: Graves’ disease
Various autoantibodies (TSH receptor, antimicrosomal, and antithyroglobulin) are detected in thyroid disorders like Hashimoto’s thyroiditis and Graves’ disease. Antimicrosomal (also called as thyroid peroxidase) and anti-thyroglobulin antibodies are observed in almost all patients with Hashimoto’s disease. TSH receptor antibodies (TRAb) are mainly tested in Graves’ disease to predict the outcome after treatment (Box 864.1).
 
Radioactive Iodine Uptake (RAIU) Test
 
This is a direct test that assesses the trapping of iodide by thyroid gland (through the iodine symporters or pumps in follicular cells) for thyroid hormone synthesis. Patient is administered a tracer dose of radioactive iodine (131I or 123I) orally. This is followed by measurement of amount of radioactivity over the thyroid gland at 2 to 6 hours and again at 24 hours. RAIU correlates directly with the functional activity of the thyroid gland. Normal RAIU is about 10-30% of administered dose at 24 hours, but varies according to the geographic location due to differences in dietary intake.
 
Causes of Increased Uptake
 
  • Hyperthyroidism due to Graves’ disease, toxic multinodular goiter, toxic adenoma, TSH-secreting tumor.
 
Causes of Decreased Uptake
 
  • Hyperthyroidism due to administration of thyroid hormone, factitious hyperthyroidism, subacute thyroiditis.
 
Uses
 
RAIU is most helpful in differential diagnosis of hyperthyroidism by separating causes into those due to increased uptake and due to decreased uptake.
 
Thyroid Scintiscanning
 
An isotope (99mTc-pertechnetate) is administered and a gamma counter assesses its distribution within the thyroid gland.
 
Interpretation
 
  • Differential diagnosis of high RAIU thyrotoxicosis:
    – Graves’ disease: Uniform or diffuse increase in uptake
    – Toxic multinodular goiter: Multiple discrete areas of increased uptake
    – Adenoma: Single area of increased uptake
  • Evaluation of a solitary thyroid nodule:
    – ‘Hot’ nodule: Hyperfunctioning
    – ‘Cold’ nodule: Non-functioning; about 20% cases are malignant.
 
Interpretation of thyroid function tests is shown in Table 164.1.
 
Table 864.1 Interpretation of thyroid function tests
Test results Interpretations
1. TSH Normal, FT4 Normal Euthyroid
2. Low TSH, Low FT4 Secondary hypothyroidism
3. High TSH, Normal FT4 Subclinical hypothyroidism
4. High TSH, Low FT4 Primary hypothyroidism
5. Low TSH, Normal FT4, Normal FT3 Subclinical hyperthyroidism
6. Low TSH, Normal FT4, High FT3 T3 toxicosis
7. Low TSH, High FT4 Primary hyperthyroidism
 
Neonatal Screening for Hypothyroidism
 
Thyroid hormone deficiency during neonatal period can cause severe mental retardation (cretinism) that can be prevented by early detection and treatment. Estimation of TSH is done on dry blood spots on filter paper or cord serum between 3rd to 5th days of life. Elevated TSH is diagnostic of hypothyroidism. In infants with confirmed hypothyroidism, RAIU (123I) scan should be done to distinguish between thyroid agenesis and dyshormonogenesis.
Box 863.1 Terminology in thyroid disorders
  • Primary hyper-/hypothyroidism: Increased or decreased function of thyroid gland due to disease of thyroid itself and not due to increased or decreased levels of TRH or TSH.
  • Secondary hyper-/hypothyroidism: Increased or decreased function of thyroid gland due to increased or decreased levels of TSH.
  • Tertiary hypothyroidism: Decreased function of thyroid gland due to decreased function of hypothalamus.
  • Subclinical thyroid disease: A condition with abnormality of thyroid hormone levels in blood but without specific clinical manifestations of thyroid disease and without any history of thyroid dysfunction or therapy.
  • Subclinical hyperthyroidism: A condition with normal thyroid hormone levels but with low or undetectable TSH level.
  • Subclinical hypothyroidism: A condition with normal thyroxine and triiodothyronine level along with mildly elevated TSH level.
Among the endocrine disorders, disorders of thyroid are common and are only next in frequency to diabetes mellitus. They are more common in women than in men. Functional thyroid disorders can be divided into two types depending on activity of the thyroid gland: hypothyroidism (low thyroid hormones), and hyperthyroidism (excess thyroid hormones). Any enlargement of thyroid gland is called as a goiter. Terminology related to thyroid disorders is shown in Box 863.1.
 
Hyperthyroidism
 
Hyperthyroidism is a condition caused by excessive secretion of thyroid hormone. Causes of hyperthyroidism are listed in Table 863.1.
 
Table 863.1 Causes of hyperthyroidism
  1. Graves’ disease (Diffuse toxic goiter)
  2. Toxicity in multinodular goiter
  3. Toxicity in adenoma
  4. Subacute thyroiditis
  5. TSH-secreting pituitary adenoma (secondary hyperthyroidism)
  6. Trophoblastic tumours that secrete TSH-like hormone: choriocarcinoma, hydatidiform mole
  7. Factitious hyperthyroidism
 
Clinical Characteristics
 
Clinical characteristics of hyperthyroidism are nervousness, anxiety, irritability, insomnia, fine tremors; weight loss despite normal or increased appetite; heat intolerance; increased sweating; dyspnea on exertion; amenorrhea and infertility; palpitations, tachycardia, cardiac arrhythmias, heart failure (especially in elderly); and muscle weakness, proximal myopathy, and osteoporosis (especially in elderly).
 
The triad of Graves’ disease consists of hyperthyroidism, ophthalmopathy (exophthalmos, lid retraction, lid lag, corneal ulceration, impaired eye muscle function), and dermopathy (pretibial myxoedema).
 
Box 863.2 Thyroid function tests in hyperthyroidism
  • Thyrotoxicosis:
    Serum TSH low or undetectable
    – Raised total T4 and free T4.
  • T3 toxicosis:
    – Serum TSH undetectable
    – Normal total T4 and free T4
    – Raised T3
Laboratory Features
 
In most patients, free serum T3 and T4 are elevated. In T3 thyrotoxicosis (5% cases of thyrotoxicosis), serum T4 levels are normal while T3 is elevated. Serum TSH is low or undetectable (< 0.1 mU/L) (Box 863.2).
 
Undetectable or low serum TSH along with normal levels of T3 and T4 is called as subclinical hyperthyroidism; subtle signs and symptoms of thyrotoxicosis may or may not be present. Subclinical hyperthyroidism is associated with risk of atrial fibrillation, osteoporosis, and progression to overt thyroid disease.
 
Features of primary and secondary hyperthyroidism are compared in Table 863.2.
 
Table 863.2 Differences between primary and secondary hyperthyroidism
Parameter Primary hyperthyroidism Secondary hyperthyroidism
1. Serum TSH Low Normal or high
2. Serum free thyroxine High High
3. TSH receptor antibodies May be positive Negative
4. Causes Graves’ disease, toxic multinodular goiter, toxic adenoma Pituitary adenoma
 
Evaluation of hyperthyroidism is presented in Figure 863.1.
 
Figure 863.1 Evaluation of hyperthyroidism
Figure 863.1 Evaluation of hyperthyroidism. TSH: thyroid stimulating hormone; FT4: free T4; FT3: free T3; TRAb: TSH receptor antibody; TRH: Thyrotropin releasing hormone
 
Hypothyroidism
 
Hypothyroidism is a condition caused by deficiency of thyroid hormones. Causes of hypothyroidism are listed in Table 863.3. Primary hypothyroidism results from deficient thyroid hormone biosynthesis that is not due to disorders of hypothalamus or pituitary. Secondary hypothyroidism results from deficient secretion of TSH from pituitary. Deficient or loss of secretion of thyro-tropin releasing hormone from hypothalamus results in tertiary hypothyroidism. Secondary and tertiary hypothyroidism are much less common than primary. Plasma TSH is high in primary and low in secondary and tertiary hypothyroidism. Differences between primary and secondary hypothyroidism are shown in Table 863.4.
 
Table 863.3 Causes of hypothyroidism 
  1. Primary hypothyroidism (Increased TSH)
    • Iodine deficiency
    • Hashimoto’s thyroiditis
    Exogenous goitrogens
    • Iatrogenic: surgery, drugs, radiation
  2. Secondary hypothyroidism (Low TSH): Diseases of pituitary
  3. Tertiary hypothyroidism (Low TSH, Low TRH): Diseases of hypothalamus
 
Table 863.4 Differences between primary and secondary hypothyroidism
Parameter Primary hypothyroidism Secondary hypothyroidism
1. Cause Hashimoto’s thyroiditis Pituitary disease
2. Serum TSH High Low
3. Thyrotropin releasing hormone stimulation test Exaggerated response No response
4. Antimicrosomal antibodies Present Absent
 
Box 863.3 Thyroid function tests in hypothyroidism
  • Primary hypothyroidism
    – Serum TSH: Increased (proportional to degree of hypofunction)
    – Free T4: Decreased
    – TRH stimulation test: Exaggerated response
  • Secondary hypothyroidism
    – Serum TSH: Decreased
    – Free T4: Decreased
    – TRH stimulation test: Absent response
  • Tertiary hypothyroidism
    – Serum TSH: Decreased
    – FT4: Decreased
    – TRH stimulation test: Delayed response
Clinical features of primary hypothyroidism are: lethargy, mild depression, disturbances in menstruation, weight gain, cold intolerance, dry skin, myopathy, constipation, and firm and lobulated thyroid gland (in Hashimoto’s thyroiditis).
 
In severe cases, myxoedema coma (an advanced stage with stupor, hypoventilation, and hypothermia) can occur.
 
Laboratory Features
 
Laboratory features in hypothyroidism are shown in Box 863.3.
 
Normal serum thyroxine (T4 and FT4) coupled with a moderately raised TSH (>10 mU/L) is referred to as subclinical hypothyroidism. It is associated with bad obstetrical outcome, poor cognitive development in children, and high risk of hypercholesterolemia and progression to overt hypothyroidism.
 
Evaluation of hypothyroidism is presented in Figure 863.2
 
Figure 863.2 Evaluation of hypothyroidism
Figure 863.2 Evaluation of hypothyroidism. TSH: thyroid stimulating hormone; FT4: free T4; TRH: Thyrotropin releasing hormone
The ovaries are the sites of production of female gametes or ova by the process of oogenesis. The ova are released by the process of ovulation in a cyclical manner at regular intervals. Ovary contains numerous follicles that contain ova in various stages of development. During each menstrual cycle, up to 20 primordial follicles are activated for maturation; however, only one follicle becomes fully mature; this dominant follicle ruptures to release the secondary oocyte from the ovary. Maturation of the follicle is stimulated by follicle stimulating hormone (FSH) secreted by anterior pituitary (Figure 862.1). Maturing follicle secretes estrogen that causes proliferation of endometrium of the uterus (proliferative phase). Follicular cells also secrete inhibin which regulates release of FSH by the anterior pituitary. Fall in FSH level is followed by secretion of luteinizing hormone (LH) by the anterior pituitary (LH surge). This causes follicle to rupture and the ovum is expelled into the peritoneal cavity near the fimbrial end of the fallopian tube. The fallopian tubes conduct ova from the ovaries to the uterus. Fertilization of ovum by the sperm occurs in the fallopian tube.
 
Figure 862.1 The hypothalamus pituitary ovarian axis
Figure 862.1 The hypothalamus-pituitary-ovarian axis 
 
The ovum consists of the secondary oocyte, zona pellucida and corona radiata. The ruptured follicle in the ovary collapses and fills with blood clot (corpus luteum). LH converts granulose cells in the follicle to lutein cells which begin to secrete progesterone. Progesterone stimulates secretion from the endometrial glands (secretory phase) that were earlier under the influence of estrogen. Rising progesterone levels inhibit LH production from the anterior pituitary. Without LH, the corpus luteum regresses and becomes functionless corpus albicans. After regression of corpus luteum, production of estrogen and progesterone stops and endometrium collapses, causing onset of menstruation. If the ovum is fertilized and implanted in the uterine wall, human chorionic gonadotropin (hCG) is secreted by the developing placenta into the maternal circulation. Human chorionic gonadotropin maintains the corpus luteum for secetion of estrogen and progesterone till 12th week of pregnancy. After 12th week, corpus luteum regresses to corpus albicans and the function of synthesis of estrogen and progesterone is taken over by placenta till parturition.
 
The average duration of the normal menstrual cycle is 28 days. Ovulation occurs around 14th day of the cycle. The time interval between ovulation and menstruation is called as luteal phase and is fairly constant (14 days) (Figure 862.2).
 
Figure 862.2 Normal menstrual cycle
Figure 862.2 Normal menstrual cycle
 
Causes of Female Infertility
 
Causes of female infertility are shown in Table 862.1.
 
Table 862.1 Causes of female infertility
1. Hypothalamic-pituitary dysfunction:
  • Hypothalamic causes
    – Excessive exercise
    – Excess stress
    – Low weight
    – Kallman’s syndrome
    Idiopathic
  • Pituitary causes
    – Hyperprolactinemia
    Hypopituitarism (Sheehan’s syndrome, Simmond’s disease)
    – Craniopharyngioma
    – Cerebral irradiation
 2. Ovarian dysfunction:
  • Polycystic ovarian disease (Stein-Leventhal syndrome)
  • Luteinized unruptured follicle
  • Turner’s syndrome
  • Radiation or chemotherapy
  • Surgical removal of ovaries
  • Idiopathic
 3. Dysfunction in passages:
  • Fallopian tubes
    Infections: Tuberculosis, gonorrhea, Chlamydia
    – Previous surgery (e.g. laparotomy)
    – Tubectomy
    Congenital hypoplasia, non-canalization
    Endometriosis
  • Uterus
    – Uterine malformations
    – Asherman’s syndrome
    – Tuberculous endometritis
    Fibroid
  • Cervix: Sperm antibodies
  • Vagina: Septum
 4. Dysfunction of sexual act: Dyspareunia
 
Investigations
 
Evaluation of female infertility is shown in Figure 862.3.
 
Figure 862.3 Evaluation of female infertility
Figure 862.3 Evaluation of female infertility. FSH: Follicle stimulating hormone; LH: Luteinizing hormone; DHEA-S: Dihydroepiandrosterone; TSH: Thyroid stimulating hormone; ↑ : Increased; ↓ : Decreased
 
Tests for Ovulation
 
Most common cause of female infertility is anovulation.
 
  1. Regular cycles, mastalgia, and laparoscopic direct visualization of corpus luteum indicate ovulatory cycles. Anovulatory cycles are clinically characterized by amenorrhea, oligomenorrhea, or irregular menstruation. However, apparently regular cycles may be associated with anovulation.
  2. Endometrial biopsy: Endometrial biopsy is done during premenstrual period (21st-23rd day of the cycle). The secretory endometrium during the later half of the cycle is an evidence of ovulation.
  3. Ultrasonography (USG): Serial ultrasonography is done from 10th day of the cycle and the size of the dominant follicle is measured. Size >18 mm is indicative of imminent ovulation. Collapse of the follicle with presence of few ml of fluid in the pouch of Douglas is suggestive of ovulation. USG also is helpful for treatment (i.e. timing of coitus or of intrauterine insemination) and diagnosis of luteinized unruptured follicle (absence of collapse of dominant follicle). Transvaginal USG is more sensitive than abdominal USG.
  4. Basal body temperature (BBT): Patient takes her oral temperature at the same time every morning before arising. BBT falls by about 0.5°F at the time of ovulation. During the second (progestational) half of the cycle, temperature is slightly raised above the preovulatory level (rise of 0.5° to 1°F). This is due to the slight pyrogenic action of progesterone and is therefore presumptive evidence of functional corpus luteum.
  5. Cervical mucus study:
    Fern test: During estrogenic phase, a characteristic pattern of fern formation is seen when cervical mucus is spread on a glass slide (Figure 862.4). This ferning disappears after the 21st day of the cycle. If previously observed, its disappearance is presumptive evidence of corpus luteum activity.
    Spinnbarkeit test: Cervical mucus is elastic and withstands stretching upto a distance of over 10 cm. This phenomenon is called Spinnbarkeit or the thread test for the estrogen activity. During the secretory phase, viscosity of the cervical mucus increases and it gets fractured when stretched. This change in cervical mucus is evidence of ovulation.
  6. Vaginal cytology: Karyopyknotic index (KI) is high during estrogenic phase, while it becomes low in secretory phase. This refers to percentage of super-ficial squamous cells with pyknotic nuclei to all mature squamous cells in a lateral vaginal wall smear. Usually minimum of 300 cells are evaluated. The peak KI usually corresponds with time of ovulation and may reach upto 50 to 85.
  7. Estimation of progesterone in mid-luteal phase (day 21 or 7 days before expected menstruation): Progesterone level > 10 nmol/L is a reliable evidence of ovulation if cycles are regular (Figure 862.5). A mistimed sample is a common cause of abnormal result.
 
Figure 862.4 Ferning of cervical mucosa
Figure 862.4 Ferning of cervical mucosa
 
Figure 862.5 Serum progesterone during normal menstrual cycle
Figure 862.5 Serum progesterone during normal menstrual cycle
 
Tests to Determine the Cause of Anovulation
 
  1. Measurement of LH, FSH, and estradiol during days 2 to 6: All values are low in hypogonadotropic hypogonadism (hypothalamic or pituitary failure).
  2. Measurement of TSH, prolactin, and testosterone if cycles are irregular or absent:
    Increased TSH: Hypothyroidism
    Increased prolactin: Pituitary adenoma
    Increased testosterone: Polycystic ovarian disease (PCOD), congenital adrenal hyperplasia (To differentiate PCOD from congenital adrenal hyperplasia, ultrasound and estimation of dihydroepiandrosterone or DHEA are done).
  3. Transvaginal ultrasonography: This is done for detection of PCOD.
 
Investigations to Assess Tubal and Uterine Status
 
  1. Infectious disease: These tests include endometrial biopsy for tuberculosis and test for chlamydial IgG antibodies for tubal factor in infertility.
  2. Hysterosalpingography (HSG): HSG is a radiological contrast study for investigation of the shape of the uterine cavity and for blockage of fallopian tubes (Figure 862.6). A catheter is introduced into the cervical canal and a radiocontrast dye is injected into the uterine cavity. A real time X-ray imaging is carried out to observe the flow of the dye into the uterine cavity, tubes, and spillage into the uterine cavity.
  3. Hysterosalpingo-contrast sonography: A catheter is introduced into the cervical canal and an echocontrast fluid is introduced into the uterine cavity. Shape of the uterine cavity, filling of fallopian tubes, and spillage of contrast fluid are noted. In addition, ultrasound scan of the pelvis provides information about any fibroids or polycystic ovarian disease.
  4. Laparoscopy and dye hydrotubation test with hysteroscopy: In this test, a cannula is inserted into the cervix and methylene blue dye is introduced into the uterine cavity. If tubes are patent, spillage of the dye is observed from the ends of both tubes. This technique also allows visualization of pelvic organs, endometriosis, and pelvic adhesions. If required, endometriosis and tubal blockage can be treated during the procedure.
 
Possible pregnancy and active pelvic or vaginal infection are contraindications to tubal patency tests.
 
Figure 862.6 Hysterosalpingography
Figure 862.6 Hysterosalpingography
The male reproductive system consists of testes (paired organs located in the scrotal sac that produce spermatozoa and secrete testosterone), a paired system of ducts comprising of epididymis, vasa deferentia, and ejaculatory ducts (collect, store, and conduct spermatozoa), paired seminal vesicles and a single prostate gland (produce nutritive and lubricating seminal fluid), bulbourethral glands of Cowper (secrete lubricating mucus), and penis (organ of copulation).
 
The hypothalamus secretes gonadotropin releasing hormone (GnRH) that regulates the secretion of the two gonadotropins from the anterior pituitary: luteinizing hormone (LH) and follicle stimulating hormone (FSH) (Figure 861.1). Luteinizing hormone primarily stimulates the production and secretion of testosterone from Leydig cells located in the interstitial tissue of the testes. Testosterone stimulates spermatogenesis, and plays a role in the development of secondary sexual characters. Testosterone needs to be converted to an important steroidal metabolite, dihydrotestosterone within cells to perform most of its androgenic functions. Testosterone inhibits LH secretion by negative feedback. Follicle stimulating hormone acts on Sertoli cells of seminiferous tubules to regulate the normal maturation of the sperms. Sertoli cells produce inhibin that controls FSH secretion by negative feedback.
 
Figure 861.1 Hypothalamus-pituitary-testis axis. + indicates stimulation; – indicates negative feedback
Figure 861.1 Hypothalamus-pituitary-testis axis. + indicates stimulation; – indicates negative feedback
 
During sexual intercourse, semen is deposited into the vagina. Liquefaction of semen occurs within 20-30 minutes due to proteolytic enzymes of prostatic fluid. For fertilization to occur in vivo, the sperm must undergo capacitation and acrosome reaction. Capacitation refers to physiologic changes in sperms that occur during their passage through the cervix of the female genital tract. With capacitation, the sperm acquires (i) ability to undergo acrosome reaction, (ii) ability to bind to zona pellucida, and (iii) hypermotility. Sperm then travels through the cervix and uterus up to the fallopian tube. Binding of sperm to zona pellucida induces acrosomal reaction (breakdown of outer plasma membrane by enzymes of acrosome and its fusion with outer acrosomal membrane, i.e. loss of acrosome). This is necessary for fusion of sperm and oocyte membranes. Acrosomal reaction and binding of sperm and ovum surface proteins is followed by penetration of zona pellucida of ovum by the sperm. Following penetration by sperm, hardening of zona pellucida occurs that inhibits penetration by additional sperms. A sperm penetrates and fertilizes the egg in the ampullary portion of the fallopian tube (Figure 861.2).
 
Figure 861.2 Steps before and after fertilization of ovum
Figure 861.2 Steps before and after fertilization of ovum
 
Causes of Male Infertility
 
Causes of male infertility are listed in Table 861.1.
 
Table 861.1 Causes of male infertility 
2. Hypothalamic-pituitary dysfunction (hypogonadotropic hypogonadism)
3. Testicular dysfunction:
  • Radiation, cytotoxic drugs, antihypertensives, antidepressants
  • General factors like stress, emotional factors, drugs like marijuana, anabolic steroids, and cocaine, alcoholism, heavy smoking, undernutrition
  • Mumps orchitis after puberty
  • Varicocele (dilatation of pampiniform plexus of scrotal veins)
  • Undescended testes (cryptorchidism)
  • Endocrine disorders like diabetes mellitus, thyroid dysfunction
  • Genetic disorders: Klinefelter’s syndrome, microdeletions in Y chromosome, autosomal Robertsonian translocation, immotile cilia syndrome (Kartagener’s syndrome), cystic fibrosis, androgen receptor gene defect
4. Dysfunction of passages and accessory sex glands:
 5. Dysfunction of sexual act:
  • Defects in ejaculation: retrograde (semen is pumped backwards in to the bladder), premature, or absent
  • Hypospadias
 
Investigations of Male Infertility
 
  1. History: This includes type of lifestyle (heavy smoking, alcoholism), sexual practice, erectile dysfunction, ejaculation, sexually transmitted diseases, surgery in genital area, drugs, and any systemic illness.
  2. Physical examination: Examination of reproductive system should includes testicular size, undescended testes, hypospadias, scrotal abnormalities (like varicocele), body hair, and facial hair. Varicocele can occur bilaterally and is the most common surgically removable abnormality causing male infertility.
  3. Semen analysis: See article Semen Analysis. Evaluation of azoospermia is shown in Figure 861.3. Evaluation of low semen volume is shown in Figure 861.4.
  4. Chromosomal analysis: This can reveal Klinefelter’s syndrome (e.g. XXY karyotype) (Figure 861.5), deletion in Y chromosome, and autosomal Robertsonian translocation. It is necessary to screen for cystic fibrosis carrier state if bilateral congenital absence of vas deferens is present.
  5. Hormonal studies: This includes measurement of FSH, LH, and testosterone to detect hormonal abnormalities causing testicular failure (Table 861.2).
  6. Testicular biopsy: Testicular biopsy is indicated when differentiation between obstructive and non-obstructive azoospermia is not evident (i.e. normal FSH and normal testicular volume).
 
Table 861.2 Interpretation of hormonal studies in male infertility 
Follicle stimulating hormone Luteinizing hormone Testosterone Interpretation
Low Low Low Hypogonadotropic hypogonadism (Hypothalamic or pituitary disorder)
High High Low Hypergonadotropic hypogonadism (Testicular disorder)
Normal Normal Normal Obstruction of passages, dysfunction of accessory glands
 
Figure 861.3 Evaluation of azoospermia
Figure 861.3 Evaluation of azoospermia. FSH: Follicle stimulating hormone; LH: Luteinizing hormone
 
Figure 861.4 Evaluation of low semen volume
Figure 861.4 Evaluation of low semen volume
 
Figure 861.5 Karyotype in Klinefelter's Syndrome
 Figure 861.5 Karyotype in Klinefelter’s syndrome (47, XXY)
 
Common initial investigations for diagnosis of cause of infertility are listed below.
 
Anatomically, stomach is divided into four parts: cardia, fundus, body, and pyloric part. Cardia is the upper part surrounding the entrance of the esophagus and is lined by the mucus-secreting epithelium. The epithelium of the fundus and the body of the stomach is composed of different cell types including: (i) mucus-secreting cells which protect gastric mucosa from self-digestion by forming an overlying thick layer of mucus, (ii) parietal cells which secrete hydrochloric acid and intrinsic factor, and (iii) peptic cells or chief cells which secrete the proteolytic enzyme pepsinogen. Pyloric part is divided into pyloric antrum and pyloric canal. It is lined by mucus-secreting cells and gastrin-secreting neuroendocrine cells (G cells) (Figure 859.1).
 
Figure 859.1 Parts of stomach and their lining cells
Figure 859.1 Parts of stomach and their lining cells 
 
In the stomach, ingested food is mechanically and chemically broken down to form semi-digested liquid called chyme. Following relaxation of pyloric sphincter, chyme passes into the duodenum.
 
There are three phases of gastric acid secretion: cephalic, gastric, and intestinal.
 
  • Cephalic or neurogenic phase: This phase is initiated by the sight, smell, taste, or thought of food that causes stimulation of vagal nuclei in the brain. Vagus nerve directly stimulates parietal cells to secrete acid; in addition, it also stimulates antral G cells to secrete gastrin in blood (which is also a potent stimulus for gastric acid secretion) (Figure 859.2). Cephalic phase is abolished by vagotomy.
  • Gastric phase: Entry of swallowed food into the stomach causes gastric distension and induces gastric phase. Distension of antrum and increase in pH due to neutralization of acid by food stimulate antral G cells to secrete gastrin into the circulation. Gastrin, in turn, causes release of hydrochloric acid from parietal cells.
  • Intestinal phase: Entry of digested proteins into the duodenum causes an increase in acid output from the stomach. It is thought that certain hormones and absorbed amino acids stimulate parietal cells to secrete acid.
 
The secretion from the stomach is called as gastric juice. The chief constituents of the gastric juice are:
 
  • Hydrochloric acid (HCl): This is secreted by the parietal cells of the fundus and the body of the stomach. HCl provides the high acidic pH necessary for activation of pepsinogen to pepsin. Gastric acid secretion is stimulated by histamine, acetylcholine, and gastrin (Figure 859.2). HCl kills most microorganisms entering the stomach and also denatures proteins (breaks hydrogen bonds making polypeptide chains to unfold). Its secretion is inhibited by somatostatin (secreted by D cells in pancreas and by mucosa of intestine), gastric inhibitory peptide (secreted by K cells in duodenum and jejunum), prostaglandin, and secretin (secreted by S cells in duodenum).
  • Pepsin: Pepsin is secreted by chief cells in stomach. Pepsin causes partial digestion of proteins leading to the formation of large polypeptide molecules (optimal function at pH 1.0 to 3.0). Its secretion is enhanced by vagal stimulation.
  • Mucus
  • Intrinsic factor (IF): IF is necessary for absorption of vitamin B12 in the terminal ileum. It is secreted by parietal cells of stomach.
 
Figure 859.2 Stimulation of gastric acid secretion
Figure 859.2 Stimulation of gastric acid secretion. Three receptors on parietal cells stimulate acid secretion: histamine (H2) receptor, acetylcholine or cholinergic receptor, and gastrin/CCK-B receptor. Histamine is released by enterochromaffin-like cells in lamina propria. Acetylcholine is released from nerve endings. Gastrin is released from G cells in antrum (in response to amino acids in food, antral distention, and gastrin-releasing peptide). After binding to receptors, H+ is secreted in exchange for K+ by proton pump
  • Gastric intubation for gastric analysis is contraindicated in esophageal stricture or varices, active nasopharyngeal disease, diverticula, malignancy, recent history of severe gastric hemorrhage, hypertension, aortic aneurysm, cardiac arrhythmias, congestive cardiac failure, or non-cooperative patient.
  • Pyloric stenosis: Obstruction of gastric outlet can elevate gastric acid output due to raised gastrin (following antral distension).
  • Pentagastrin stimulation is contraindicated in cases with allergy to pentagastrin, and recent severe gastric hemorrhge due to peptic ulcer disease.
 
Gastric analysis is not a commonly performed procedure because of following reasons:
 
  • It is an invasive and cumbersome technique that is traumatic and unpleasant for the patient.
  • Information obtained is not diagnostic in itself.
  • Availability of better tests for diagnosis such as endoscopy and radiology (for suspected peptic ulcer or malignancy); serum gastrin estimation (for ZE syndrome); vitamin assays, Schilling test, and antiparietal cell antibodies (for pernicious anemia); and tests for Helicobacter pylori infection (in duodenal or gastric ulcer).
  • Availability of better medical line of treatment that obviates need for surgery in many patients.
  1. Hollander’s test (Insulin hypoglycemia test): In the past, this test was used for confirmation of completeness of vagotomy (done for duodenal ulcer).

    Hypoglycemia is a potent stimulus for gastric acid secretion and is mediated by vagus nerve. This response is abolished by vagotomy.

    In this test, after determining BAO, insulin is administered intravenously (0.15-0.2 units/kg) and acid output is estimated every 15 minutes for 2 hours (8 post-stimulation samples). Vagotomy is considered as complete if, after insulin-induced hypoglycemia (blood glucose < 45 mg/dl), no acid output is observed within 45 minutres.

    The test gives reliable results only if blood glucose level falls below 50 mg/dl at some time following insulin injection. It is best carried out after 3-6 months of vagotomy.

    The test is no longer recommended because of the risk associated with hypoglycemia. Myocardial infarction, shock, and death have also been reported.

  2. Fractional test meal: In the past, test meals (e.g. oat meal gruel, alcohol) were administered orally to stimulate gastric secretion and determine MAO or PAO. Currently, parenteral pentagastrin is the gastric stimulant of choice.

  3. Tubeless gastric analysis: This is an indirect and rapid method for determining output of free hydrochloric acid in gastric juice. In this test, a cationexchange resin tagged to a dye (azure A) is orally administered. In the stomach, the dye is displaced from the resin by the free hydrogen ions of the hydrochloric acid. The displaced azure A is absorbed in the small intestine, enters the bloodstream, and is excreted in urine. Urinary concentration of the dye is measured photometrically or by visual comparison with known color standards. The quantity of the dye excreted is proportional to the gastric acid output. However, if kidney or liver function is impaired, false results may be obtained. The test is no longer in use.

  4. Spot check of gastric pH: According to some investigators, spot determination of pH of fasting gastric juice (obtained by nasogastric intubation) can detect the presence of hypochlorhydria (if pH>5.0 in men or >7.0 in women).

  5. Congo red test during esophagogastroduodenoscopy: This test is done to determine the completeness of vagotomy. Congo red dye is sprayed into the stomach during esophagogastroduodenoscopy; if it turns red, it indicates presence of functional parietal cells in stomach with capacity of producing acid.
 
REFERENCE RANGES
 
  • Volume of gastric juice: 20-100 ml
  • Appearance: Clear
  • pH: 1.5 to 3.5
  • Basal acid output: Up to 5 mEq/hour
  • Peak acid output: 1 to 20 mEq/hour
  • Ratio of basal acid output to peak acid output: <0.20 or < 20%
In gastric analysis, amount of acid secreted by the stomach is determined on aspirated gastric juice sample. Gastric acid output is estimated before and after stimulation of parietal cells (i.e. basal and peak acid output). This test was introduced in the past mainly for the evaluation of peptic ulcer disease (to assess the need for operative intervention). However, diminishing frequency of peptic ulcer disease and availability of safe and effective medical treatment have markedly reduced the role of surgery.
 
  1. To determine the cause of recurrent peptic ulcer disease:
    To detect Zollinger-Ellison (ZE) syndrome: ZE syndrome is a rare disorder in which multiple mucosal ulcers develop in the stomach, duodenum, and upper jejunum due to gross hypersecretion of acid in the stomach. The cause of excess secretion of acid is a gastrin-producing tumor of pancreas. Gastric analysis is done to detect markedly increased basal and pentagastrinstimulated gastric acid output for diagnosis of ZE syndrome (and also to determine response to acidsuppressant therapy). However, a more sensitive and specific test for diagnosis of ZE syndrome is measurement of serum gastrin (fasting and secretin-stimulated).
    To decide about completeness of vagotomy following surgery for peptic ulcer disease: See Hollander’s test.
  2. To determine the cause of raised fasting serum gastrin level: Hypergastrinemia can occur in achlorhydria, Zollinger-Ellison syndrome, and antral G cell hyperplasia.
  3. To support the diagnosis of pernicious anemia (PA): Pernicious anemia is caused by defective absorption of vitamin B12 due to failure of synthesis of intrinsic factor secondary to gastric mucosal atrophy. There is also absence of hydrochloric acid in the gastric juice (achlorhydria). Gastric analysis is done for demonstration of achlorhydria if facilities for vitamin assays and Schilling’s test are not available (Achlorhydria by itself is insufficient for diagnosis of PA).
  4. To distinguish between benign and malignant ulcer: Hypersecretion of acid is a feature of duodenal peptic ulcer, while failure of acid secretion (achlorhydria) occurs in gastric carcinoma. However, anacidity occurs only in a small proportion of cases with advanced gastric cancer. Also, not all patients with duodenal ulcer show increased acid output.
  5. To measure the amount of acid secreted in a patient with symptoms of peptic ulcer dyspepsia but normal X-ray findings: Excess acid secretion in such cases is indicative of duodenal ulcer. However, hypersecretion of acid does not always occur in duodenal ulcer.
  6. To decide the type of surgery to be performed in a patient with peptic ulcer: Raised basal as well as peak acid outputs indicate increased parietal cell mass and need for gastrectomy. Raised basal acid output with normal peak output is an indication for vagotomy.
To assess gastric acid secretion, acid output from the stomach is measured in a fasting state and after injection of a drug which stimulates gastric acid secretion.
 
Basal acid output (BAO) is the amount of hydrochloric acid (HCl) secreted in the absence of any external stimuli (visual, olfactory, or auditory).
 
Maximum acid output (MAO) is the amount of hydrochloric acid secreted by the stomach following stimulation by pentagastrin. MAO is calculated from the first four 15-minute samples after stimulation.
 
Peak acid output (PAO) is calculated from the two highest consecutive 15-minute samples. It indicates greatest possible acid secretory capacity and is preferred over MAO as it is more reproducible.
 
Acidity is estimated by titration.
 
Collection of Sample
 
All drugs that affect gastric acid secretion (e.g. antacids, anticholinergics, cholinergics, H2-receptor antagonists, antihistamines, tranquilizers, antidepressants, and carbonic anhydrase inhibitors) should be withheld for 24 hours before the test. Proton pump inhibitors should be discontinued 5 days prior to the test. Patient should be relaxed and free from all sources of sensory stimulation.
 
Patient should drink or eat nothing after midnight.
 
Gastric juice can be aspirated through an oral or nasogastric tube (polyvinyl chloride, silicone, or polyurethane) or during endoscopy.
 
Oral or nasogastric tube (Figure 855.1) is commonly used. It is a flexible tube having a small diameter and a bulbous end that is made heavy by a small weight of lead. The end is perforated with small holes to allow entry of gastric juice into the tube. As the end is radiopaque, the tube can be positioned in the most dependent part of the stomach under fluoroscopic or X-ray guidance. The tube is lubricated and can be introduced either through the mouth or the nose. The patient is either sitting or reclining on left side. The tube has three or four markings on its outer surface that correspond with distance of the tip of the tube from the teeth, i.e. 40 cm (tip to cardioesophageal junction), 50 cm (body of stomach), 57 cm (pyloric antrum), and 65 cm (duodenum). The position of the tube can be verified either by fluoroscope or by ‘water recovery test’. In the latter test, 50 ml of water is introduced through the tube and aspirated again; recovery of > 90% of water is indicative of proper placement. The tube is usually positioned in the antrum. A syringe is attached to the outer end of the tube for the aspiration of gastric juice.
 
Figure 855.1 Oral or nasogastric Ryles tube
Figure 855.1 Oral or nasogastric Ryle’s tube. The tube is marked at 40, 50, 57, and 65 cm with radiopaque lines for accurate placement. The tip is bulbous and contains a small weight of lead to assist the passage during intubation and to know the position under fluoroscopy or X-ray guidance. There are four perforations or eyes to aspirate contents from the stomach through a syringe attached to the base
 
For estimation of BAO, sample is collected in the morning after 12-hour overnight fast. Gastric secretion that has accumulated overnight is aspirated and discarded. This is followed by aspiration of gastric secretions at 15-minute intervals for 1 hour (i.e. total 4 consecutive samples are collected). All the samples are centrifuged to remove any particulate matter. Each 15-minute sample is analyzed for volume, pH, and acidity. The acid output in the four samples is totaled and the result is expressed as concentration of acid in milliequivalents per hour or in mmol per hour.
 
After the collection of gastric juice for determination of BAO, patient is given a subcutaneous or intramuscular injection of pentagastrin (6 μg/kg of body weight), and immediately afterwards, gastric secretions are aspirated at 15-minute intervals for 1 hour (for estimation of MAO or PAO). MAO is calculated from the first four 15-minute samples after stimulation. PAO is calculated from two consecutive 15-minute samples showing highest acidity.
 
Titration
 
Box 855.1 Determination of basal acid output, maximum acid output, and peak acid output
 
  • Basal acid output (BAO)= Total acid content in all four 15-minute basal samples in mEq/L
  • Maximum acid output (MAO) = Total acid content in all four 15-minute post-pentagastrin samples in mEq/L
  • Peak acid output (PAO) = Sum of two consecutive 15-minute post-pentagastrin samples showing highest acidity ×2 (mEq/L)
Gastric acidity is estimated by titration, with the end point being determined either by noting the change in color of the indicator solution or till the desired pH is reached.
 
In titration, a solution of alkali (0.1 N sodium hydroxide) is added from a graduated vessel (burette) to a known volume of acid (i.e. gastric juice) till the end point or equivalence point of reaction is reached. The concentration of acid is then determined from the concentration and volume of alkali required to neutralize the particular volume of gastric juice. Concentration of acid is expressed in terms of milliequivalents per liter or mmol per liter.
 
Free acidity refers to the concentration of HCl present in a free, uncombined form in a solution. The volume of alkali added to the gastric juice till the Topfer’s reagent (an indicator added earlier to the gastric juice) changes color or when the pH (as measured by the pH meter) reaches 3.5 is a measure of free acidity. A screening test can be carried out for the presence of free HCl in the gastric juice. If red color develops after addition of a drop of Topfer’s reagent to an aliquot of gastric juice, free HCl is present and the diagnosis of pernicious anaemia (achlorhydria) can be excluded.
 
Combined acidity refers to the amount of HCl combined with proteins and mucin and also includes small amount of weak acids present in gastric juice.
 
Total acidity is the sum of free and combined acidity. The amount of alkali added to the gastric juice till phenolphthalein indicator (added earlier to the gastric juice) changes color is a measure of total acidity (Box 855.1).
 
Interpretation of Results
 
  1. Volume: Normal total volume is 20-100 ml (usually < 50 ml). Causes of increased volume of gastric juice are—
    • Delayed emptying of stomach: pyloric stenosis
    • Increased gastric secretion: duodenal ulcer, Zollinger-Ellison syndrome.
  2. Color: Normal gastric secretion is colorless, with a faintly pungent odor. Fresh blood (due to trauma, or recent bleeding from ulcer or cancer) is red in color. Old hemorrhage produces a brown, coffee-ground like appearance (due to formation of acid hematin). Bile regurgitation produces a yellow or green color.
  3. pH: Normal pH is 1.5 to 3.5. In pernicious anemia, pH is greater than 7.0 due to absence of HCl.
  4. Basal acid output:
    • Normal: Up to 5 mEq/hour.
    • Duodenal ulcer: 5-15 mEq/hour.
    • Zollinger-Ellison syndrome: >20 mEq/hour.
    Normal BAO is seen in gastric ulcer and in some patients with duodenal ulcer.
  5. Peak acid output:
    • Normal: 1-20 mEq/hour.
    • Duodenal ulcer: 20-60 mEq/hour.
    • Zollinger-Ellison syndrome: > 60 mEq/hour.
    • Achlorhydria: 0 mEq/hour.
    Normal PAO is seen in gastric ulcer and gastric carcinoma. Values up to 60 mEq/hour can occur in some normal individuals and in some patients with Zollinger-Ellison syndrome.
    In pernicious anemia, there is no acid output due to gastric mucosal atrophy. Achlorhydria should be diagnosed only if there is no free HCl even after maximum stimulation.
  6. Ratio of basal acid output to peak acid output (BAO/PAO):
    • Normal: < 0.20 (or < 20%).
    • Gastric or duodenal ulcer: 0.20-0.40 (20-40%).
    • Duodenal ulcer: 0.40-0.60 (40-60%).
    • Zollinger-Ellison syndrome: > 0.60 (> 60%).
    Normal values occur in gastric ulcer or gastric carcinoma.
 
Conditions associated with change in gastric acid output are listed in Table 855.1.
 
It is to be noted that values of acid output are not diagnostic by themselves and should be correlated with clinical, radiological, and endoscopic features.
 
Table 855.1 Causes of alterations in gastric acid output
Increased gastric acid output Decreased gastric acid output
• Duodenal ulcer Chronic atrophic gastritis
• Zollinger-Ellison syndrome     1. Pernicious anemia
Hyperplasia of antral G cells     2. Rheumatoid arthritis
Systemic mastocytosis     3. Thyrotoxicosis
• Basophilic leukemia • Gastric ulcer
  • Gastric carcinoma
  • Chronic renal failure
  • Post-vagotomy
  • Post-antrectomy

Bioethics

  • 04 Sep 2017
Bioethics is the study of the ethical issues emerging from advances in biology and medicine. It is also moral discernment as it relates to medical policy and practice. Bioethicists are concerned with the ethical questions that arise in the relationships among life sciences, biotechnology, medicine, politics, law, and philosophy. It includes the study of values ("the ethics of the ordinary") relating to primary care and other branches of medicine.
Animal biotechnology is a branch of biotechnology in which molecular biology techniques are used to genetically engineer (i.e. modify the genome of) animals in order to improve their suitability for pharmaceutical, agricultural or industrial applications. Animal biotechnology has been used to produce genetically modified animals that synthesize therapeutic proteins, have improved growth rates or are resistant to disease.
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