Cerebrospinal Fluid

                                              Cerebrospinal Fluid (CSF)

                                             PKGhatak, MD

The previously held view of the formation and circulation of the cerebrospinal fluid (CSF) has undergone modifications because current reproducible and non-interventional methods of investigation, like MRI and molecular and biological biology, discovered newer facts that contradicted the past theory.

To update the current thinking, a brief review of the histology of the Choroid plexus, Ventricles of the brain and Arachnoid granulations is necessary.

Choroid plexus.

The Ependymal cells of the choroid plexus secrete the CSF by an active process. The central capillary of the choroid plexus is lined with one layer of fenestrated cuboidal cells. The albumin content of CSF is much lower than plasma. The transport of water across the ependymal cells of the carotid plexus is carried out by separate transport proteins, one for the ventricular side and the other for the capillary side. It is an active process that requires energy from ATP and likely also from K / Cl transporter. About 30 % of the total water volume of CSF comes from the inter-neuronal space, generated from the metabolic activities of the nerve cells, like Lymph formation in the other organs. There are to and fro moments of fluid between interstitial fluid and CSF.

Blood Brain Barrier.

This special characteristic of the blood vessels of the brain is due to the tight seal between the endothelial cells of the capillaries and supplemented by perivascular feet of astrocytes surround the basement membrane. In two locations this barrier is absent namely the choroid plexus and posterior pituitary gland.

Arachnoid Granulation:

Arachnoid granulations are collections of capillary networks kept suspended into the large veins of the subarachnoid space. The anatomical structure suggests arachnoid granulations are filters - a one way passage of CSF into the venous blood, getting rid of waste products and excess water. But that is not the case. Arachnoid granulation plays a minor role in this respect.

The perineural space along the cranial nerves and spinal nerves and the perivascular space known as Virchow Robin spaces are the main routes of drainage and filter of CSF into the general lymphatic system. This is specially evident in the Olfactory nerve as it travels through the cribriform plate of the nose.

Circulation of CSF:

  

The circulation of CSF in the brain and spinal cord.

The circulation of the CSF is an active process by the synchronous motion of cilia lining the surface of the ventricles and the central canal of the spinal cord. The CSF exits the brain through two openings of Luschka in the hindbrain and circulates in the subarachnoid space. The mechanism of a steady state of CSF formation, circulation and drainage has undergone many modifications. The circulation is pulsatile in nature due to and from movement of the CSF. The interstitial fluid exchange with CSF is a major component of circulation. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates. The general lymphatic system of the body is the main route of drainage of waste products of the brain and an entry point of the immune system in the brain.

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What Cerebellum Does

 

                                           What Cerebellum Does

                                        PKGhatak, MD

The human cerebellum occupies a small space at the back of the head, just above the neck, and it is a part of the hindbrain. Sensory information from joints, tendons and soft tissues from the limbs and trunk travel to the cerebellum. The motor stimuli coming from the cerebrum motor cortex, make connections with the nuclei of the cerebellum before reaching the lower motor nuclei of the spinal nerves and the cranial nerves. This interconnection of the motor cortex with the cerebellum results in a smooth sustained movement of the body, able to maintain the head position in space and in relation to the rest of the body and keep balance without falling. And that much knowledge people had till 1990.

Now the cerebellum is a subject of intense research for a variety of reasons.

Research in developmental biology documented three separate stages of growth of the cerebellum in humans. As the forebrain is added, the cerebral cortex, which has increased the mental faculties, knowledge gained about self, mind, higher state of consciousness, language, and development of culture has made humans as humans. But the cerebellum did not lag behind.

The growth of the cerebellum is more spectacular than the cerebral cortex. Cerebellum weighs 150 grams and contains 70 billion neurons, whereas the cerebral cortex weighs 1300 grams but contains only 16 billion neurons. The surface area of the cerebellar cortex is 1500 square centimeters, which is about 80 % of the surface area of the cerebral cortex. The cerebellar cortical folds are arranged like pages of a book - lots of surface area in a small space.

Compared with the cerebral cortex the layout of neurons and their connections in the cerebellum is much simpler and more uniform. Cerebellum receives input and sends out output to the same side of the body that is also a contrast with the cerebrum which controls the opposite side of the body. The central part of the cerebellum is old, but the lateral parts, the cerebellar hemispheres, kept pace with the growth of the cerebrum.

Cerebellum is the site of the formation and storage of working memory and the integration of automated sequences of thoughts and actions. This results in developing behavioral patterns, speech, dexterity of complex movements, a skill needed for technological advances and language development.

In association with the cerebrum, it forms kinetic memory, plans coordinated muscle movement patterns, retains reflex memory for self preservation and executes normal speech.

Cerebellum with two way communication with the thalamus and basal ganglia and receives direct input from the spinocerebellar tract and maintains balance and a stable head position both in states of body movements and at rest.

Vestibular sensory information is closely monitored by the cerebellum, that information is used to control conjugate movements of eyes, prevent double vision and reflex eye movements.

Rapid eye movement (REM) sleep includes Implicit memory involving perception and body movements. Implicit memory uses cerebellar retained memories.

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Science of Skin Color

 

                                            Science of Human skin color

                                           PKGhatak, MD

The skin is one of the body's large organs. The color of the skin prevents or minimizes the harmful effects of Ultra Violet (UV) light of the sun.

The darker the shade of color, the lesser amount of UV light penetrates the skin and decreases Vitamin D synthesis, the reverse is true for the lighter shades of color. It is said that women have lighter skin color because more vitamin D is needed for childbearing.

Not every part of the skin of an individual has the same shade of color and variability depends on the degree of exposure to sunlight. The sole of the feet and palms of the hands have different thicknesses of skin and a much lighter color, and that lighter shade is most noticeable in very dark colored people.

Theory of color variation in humans.

Scientific communities believe that the human race originated in equatorial Africa. Having dark skin gave humans an advantage over the other predators to hunt for a longer time each day. Because the black skin color developed as the coarse hairs were replaced by fine body hair. This combination allowed the body to avoid overheating. That advantage led to a population boom and subsequent migration of people to other lands. When people settled in the subtropical area, their dark skin turned to a disadvantage; the lack of calcium produced weaker siblings, and most did not survive beyond their early childhood. A genetic mutation made the color of the skin lighter shades which allowed more UV light to penetrate the skin and generate more vitamin D, and the population bounced back.

The so called white colored skin is the color of the pale white color of the subcutaneous tissue shining through the light-colored skin.

What are the color pigments of human skin:

Melanin is the primary color and minor color contributions come from hemoglobin, carotenoids and oxyhemoglobin.

Perception of color:

The combination of colors of melanin, oxyhemoglobin (proportional to blood flow) and carcinoids produce the final color perceived by the observer's retina.

Melanin:

Melanin is a group of chemicals very closely resemble each other in molecular structure. The skin Melanin in humans is Eumelanin and Pheomelanin. Neuromelanin is present in the brain.

Eumelanin and Pheomelanin are the same chemical but differ only in the number of polymer bonds in them.

Two colors of melanin:

Eumelanin is a dark pigment, has a range from brown to black, and Pheomelanin has a shade between yellow to pink color. The pink color of the lips is due to pheomelanin.

Eumelanin synthesis.

Amino acid Tyrosine is converted to Dihydroxyphenylalanine (DOPA) by the enzyme Tyrosine hydroxylase and in the presence of cofactor Tetrahydrobiopterin. DOPA is converted to Dopaquinone by Tyrosinase and then undergoes several steps of polymerization to form eumelanin or pheomelanin.

Site of melanin production:

Melanin is produced by the Melanocytes present in the basal layer of the skin. The pigment granules are nicely packed in an envelope and are called melanosomes. Melanosomes are carried along the long arm of the melanocyte and the pigment packets are deposited within the Granular cells of the keratinocyte layer. One melanocyte and 36 granular cells and one Langerhans cell make one keratinocyte unit. It is estimated one melanocyte can supply 500 granular cells with melanosomes in its lifetime.

Stimuli for melanin formation:

UV radiation stimulates the synthesis of melanin. A hormone, produced by the Pars Intermedia of the Pituitary gland, Pro-Opiomelanocortin, is turned into Alpha Menaocytotropic hormone (alpha MSH). UV light also increases ACTH (adrenocorticotropic hormone) secretion. MSH and ACTH increase melanin production. Androgen also influences melanin deposit of pigment in the form of male patterns.

Genes controlling Melanin.

In humans chromosome 11 is the primary chromosome and three additional chromosomes, 17, 6 and 13 have also influence melanin. The location of the genes on these chromosomes are 11q24.2, 17q23.2, 6q25.1 and 13q33.2.

Defective genes and abnormal skin color:

1. Albinism.  It is a Hereditary disease due to an inheritance of defective genes. Skin, hair, retina of the eyes are devoid of melanin and is known as Oculocutaneous albinism (OCA). It is inherited as an autosomal recessive trait. At present 7 varieties of OCA have been identified.

2. Hermansky-Pudlak Syndrome.  Hermansky-Pudlak patients lack skin pigment and in addition, have a tendency to bruise easily and bleed spontaneously. Patients have additional symptoms which may involve GI, Pulmonary and CNS systems. So far 11 gene mutations have been identified. This abnormality is also inherited as an autosomal recessive pattern.

3. Chediak-Higashi syndrome.  It is an autosomal recessive hereditary disorder consists of partial OCA, platelet disorder, immune deficiency due to abnormal Lysosomes and in addition to hematophagy lymphohistiocytosis syndrome

4. There are many other syndromes due to inherited defective genes. Symptoms involve various organ systems and skin color. Just to name a few – Acanthosis nigricans, Xeroderma pigmentosa, Treitz syndrome, Histiocytosis lymphadenopathy plus syndrome, Lengius syndrome, Cruzion syndrome, Incontigentia pigmenti, etc.

5. Loss of melanocytes.  Skin abrasions may peel off the basal layer of skin containing the Melanocytes, when skin lesion heals the area is devoid of skin color.

5. Autoimmune diseases. Some acquired autoimmune diseases may attack melanocytes producing pigment voided spaces.

6. Vitiligo. It is suspected to be an auto-immune disease. The color free areas are patchy and can be any spot on the skin. No genetic link has so far been documented.

7. Localized dark pigmentation on skin:

Freckles, moles, Mongolian spots on buttocks, Caffe au lait spots, and Birthmarks are examples of uneven distribution of melanin in keratinocytes. Some of these spots are transient, and others disappear and reappear later in life. Caffe au lait spots, if multiple, are associated with neurofibromatosis.

All these are benign conditions unless one starts to grow in size and becomes darker or bleeds.

 8. Melasma. Symmetrical dark patches on the face due to estrogen – progesterone concentration variation, as seen in pregnancy and menopause. Melasma has no health consequences and is important from the cosmetic point of view.

Carotenoids:

Carotenoids are Terpenoids having formula C40H56. Carotenoids are plant pigments and humans must depend on plant sources for carotenoid supply. Yellow, orange, or red vegetables and fruits contain carotenoids. They are fat soluble chemicals; animal fat is also a source like Salmon. Cooking shredded vegetables in oil increases the bioavailability of carotenoids. In humans, these molecules are antioxidants, boost immunity and provitamin A. Vitamin A is an essential vitamin for vision.

An essential organ:

The skin is an essential organ. The skin protects the body from the physical mechanical and thermal injury, prevents harmful agents from getting inside, maintains body temperature, synthesizes vitamin D, performs immune functions and the sensory receptors of pain, touch, temperature and pressure are located in the skin. Melanin in the skin protects tissues from the radiation damage of the sun.

All 8 billion people:

The color of the skin comes from one pigment - Melanin. All 8 billion people on earth have the same melanin. Color variation of the skin is due to the variation of melanin content in the skin cells.

People seeking advantage and try to divide human families into many color groups, like India did through the caste system. Businesses interested in selling their products claim about 110 tones of skin colors and have marketed matching colored products for sale.

Science has steadfastly maintained the scientific data which anyone can verify and as it stands today, all humans carry the same skin pigment melanin.

The difference in skin color is only in the view of the observer.

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Speech Disorder

 

                                                            Speech disorder

                                                    PKGhatak, MD

Speech is defined as the ability to express thoughts and feelings by articulated sounds. Language is in the same domain as speech but not the same. Language is the medium of communication with said words and symbols. 

1. Speech disorder in children is primarily developmental and congenital, after that comes others.

2. Developmental delay presents as uncoordinated brain function, manifest as Stuttering. 

3. The next group comprises Autism, dyslexia and cerebral palsy.

4. Birth defects such as tongue-tie, defects of the floor of the mouth, hare-lip and cleft palate and occiput occipito-facial abnormality. Many of them are surgically correctable.

 5. Apraxia and dysarthria are apparently similar defects but in apraxia, the brain fails to formulate a motor plan to supply nerve impulses to muscles of the larynx and vocal cords; in Dysarthria the muscles of the mouth and tongue fail to move properly due to mechanical and /or coordination abnormalities and fails to produce a normal speech.

 6. Congenital deafness or onset of early childhood deafness, leads to absent speech known as muteness. However, the mute babies did cry at the time of birth proving that absent speech in these babies comes from deafness.

Speech disorder in adults.

Speech problems in adults are always acquired after having normal speech for years.

There are three categories of this disorder - I. Transient and reversible. II. Secondary. III. Primary.

 I. Transient:

Alcohol intoxication is the most common cause of stuttering, fumbling for words and inappropriate answers. Opioid addiction and use of recreational drugs, tranquilizers, and sleeping pills are additional causes.

II. Secondary:

Multiple sclerosis (MS) produces various neurological deficits including speech. One special feature of MS is the exacerbation and remission of symptoms. ALS, Ascending paralysis, Myasthenia gravis, and myopathy of various types. and diseases involving the larynx, vocal cords and paralysis of the recurrent laryngeal nerve are further examples of speech defects.

III. Primary:

The brain is the center for speech formation (ideation), generation of motor signals and transmission of information to muscles involved in the execution and articulation of spoken words. Any disruption of the flow of information to the effector organ/tissues will adversely affect speech. Some of the pathological causes are interruption of blood supply, pressure from space occupying lesions, inflammation and infection of the brain, and traumatic injury to speech centers.

Ideation:   One can easily recall teachers telling “engage your brain before you blur out words”. That is the ideation – the speaker has instant knowledge of what he is going to say in a conversation or at the podium before a lecture. Ideation is the result of coordinated activities of many brain centers, including visual, auditory, and memory centers, which are located in the different areas of the cerebral cortex.

Motor function:   Cerebral motor center is located in the Pyramidal cortex of the brain. The axons from pyramidal neurons make synaptic connections to the lower motor neuron of the motor nuclei of cranial nerves and anterior horn cells of the spinal cord. Nerve impulses are carried to the muscles of the larynx, vocal cords, throat, lips, mouth, tongue, diaphragm and respiratory muscles of the chest wall transmitted by the axons of the lower motor neurons.

Monitoring and modification of speech are active processes and require communication via synaptic relays between various brain centers.

Localization of lesion:

At an earlier time, every speech abnormality was documented by neurological examination and then verified by autopsy. The medical practice of that time required memorizing named syndromes to identify each speech defect. Now neuroimaging by functional MRI and CT, with and without contrast, have made the diagnosis more refined and accurate at the same time names attached to lesions are not required to be remembered.

Types of speech abnormalities in adults.

 1. Broca's Aphasia.

Broca's aphasia is both a language and word disorder due to damage to Broca's area of the brain. Broca's area is a special speech center located in the left frontal lobe of the cerebral cortex. It is situated in the depth of the main horizontal fissure dividing the cortex into frontal and middle lobes and partially covered by the tip of the left temporal lobe. Anatomically, it is located in the inferior frontal gyrus. Blood supply of the Broca's area comes from the branch of the middle cerebral artery. Interruption of the blood supply produces a language and speech disorder known as Broca's Aphasia.

In Broca's Aphasia, the patient retains the capacity of Ideation but loses language due to partial loss of capacity to construct either the spoken or written language. Broca's aphasia has two components – Expressive aphasia and Receptive aphasia. In expressive aphasia, the patient is able to say important words but leaves out prepositions, pronouns and functional words. Speech becomes piecemeal, comes out in sprats and stops, says wrong words, missing the word orders. This type of speech is known as Telegraphic speech (at one time the telegram was the fastest mode of communication, but expensive and the charges were based on the number of words to be transmitted. That leads to cutting out words). In Broca's aphasia, the patient is cognizant of his disability and becomes visibly frustrated in his attempt to find his speech back.

In Receptive aphasia, the patient can speak in grammatical sentences but lacks semantic significance and exhibits trouble in comprehension.

Thrombosis or emboli obstruction of the Left middle cerebral artery produces Right sided paralysis including the right lower half of the face and loss of sensation from the right side of the body and loss of right visual field and Broca's aphasia.

 2. Wernicke's area. Werneck's area is located in the parietal cortex next to the lateral sulcus at the junction of the parietal and occipital lobes. In this area, the visual and auditory words are comprehended and an area for selecting words and phrases to construct a meaningful sentence. Patients with damaged Wernicke's area, from alcoholism and other diseases, produce articulated sentences but many lack any meaning. And some patients may speak fluently and are not aware they are uttering meaningless words. Alcoholism may lead to Korsakoff psychosis. During an episode of Korsakoff psychosis, the person speaks freely but confabulates and tells amazing stories.

3. Aphonia:

A lack of ability to produce any sound is known as aphonia. Direct injury to vocal cords, tracheostomy and bilateral recurrent laryngeal nerve damage can produce aphonia. And in addition, there are instances when a person is about to give an important talk and gets up to the podium and then is unable to make any sound. Some psychological or emotional neuronal activities overwhelm the natural order of speech making process.

4. Apraxia and Dysarthria are common in stroke and other lesions of the brain involving speech forming areas.

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Abnormal Red Cell Morphology and its Significance

 

                     Abnormal Red Blood Cell Morphology and its Significance

                                           PKGhatak, MD

Blood is known as the vital fluid and that characteristic belongs to the Red Blood Cells (RBCs). The hemoglobin, contained in the RBC, avidly combines with Carbon dioxide, a waste and toxic product of cell metabolic activities; and the RBC exchanges it for Oxygen in the lungs and carries oxygen to every living cell of the body (except the cornea).

RBC is routinely tested for - size, shape, color, volume, uniformity of distribution and for any structural anomalies; and all these are reported when a CBC (complete blood count) is ordered.

No other cell in the body has been studied that thoroughly.

A normal red cell (RBC) is a disc shaped and biconcave cell without a nucleus and inclusion bodies. The red color of the cell is due to the presence of oxyhemoglobin. RBCs appear brilliant ruby color when allowed to settle in a test tube filled with normal saline.

RBCs are 7 to 8 cu mm. in diameter, the central 1/3 is paler than the periphery. Normal RBC volume (MCV) is 80 -95 fL, and the normal number of RBCs is about 5 million per cu mm. The RBC shape is fairly inform - the RWD (red cell width distribution) is 11 to 15 %.

RBCs are formed in the bone marrow from the stem cells of the Myeloid line; Erythropoietin, a hormone produced in kidneys, stimulates RBC production. In circulation, RBCs survive for 100 – 120 days. Every part of the RBC is recycled by the spleen and other scavenger cells.

Size: Abnormal size is called Anisocytosis.

Normal size RBC is called Normocyte, Microcyte is < 7 cu mm (MCV<80 fL) and Macrocyte is over 8 cu mm (MCV >95).

When Anemia is detected, the finding is reported as either normocytic, microcytic or macrocytic anemia. Normocytic anemia is seen after a recent blood loss, like an accident, fracture of long bones, or surgery. Microcytic anemia is due to iron deficiency, thalassemia, chronic inflammation, slow GI blood loss due to cancers or bleeding duodenal/gastric ulcers and sideroblastic anemia. Macrocytic anemia is seen in Pernicious anemia, Folate and Vitamin B12 deficiencies, Steatorrhea, Myelodysplastic syndrome, Liver cirrhosis, Alcoholism and Drug- use of Hydroxyurea.

Shape: Abnormal shape is called Poikilocytosis. The abnormal shape could be Spiculated or Non-Spiculated.

Spiculated RBCs are called Burr cells, broken RBCs are known as Schistocytes resemble Napoleon hat), Helmet cells, Acanthotic cells and Dacrocytes (tear drop shaped) cells.

Non-spiculated RBC are Target cells, Ovalocytes and Stomatocytes, Pencil cells, Bite cells, Tear Drop deformities, Spherocytes and Elliptocytes.

Burr cells are seen in renal failure.

Ovalocytes and Elliptocytes are due to Hereditary causes; in addition, spherocytes are also seen in severe burns, ABO incomparable blood transfusion and acquired idiopathic hemolytic anemia.

Target cells are common in sickle cell hemoglobinopathies, thalassemia and iron deficiency anemia.

Bite cells are seen in Chronic Obstructive Pulmonary Diseases (COPD).

Stomatocytes (fish mouth like) are common in Liver disease, alcoholism, Rh-null disease and COPD.

Teardrop deformity cells are present in Myelofibrosis and pernicious anemia.

Helmet cells, Broken cells or Schistocytes in the peripheral blood are ominous signs. These cells in the blood indicate active hemolysis. Usually one of the following conditions is responsible – Decimated intravascular coagulation, TTP (thrombotic thrombocytopenic Purpura)and Thrombotic macroangiopathic anemia.

Color:

The red color of RBCs is proportional to oxyhemoglobin concentration in the cells. Based on the hemoglobin concentration per red cell, the cells are called Monochromic, Hypochromic or Hyperchromic. When color is not uniform, it is called Anisochromatic and when more than one color is present, it is called Polychromatic RBCs. Iron deficiency is the primary cause of hypochromia, and hyperchromatic is seen in sickle cell disease. Macrocytes in severe liver disease and Thalassemia, the RBCs can also be Hyperchromatic, this combination is called Leptocytes.

Increased turnover of RBC in the bone marrow results in the presence of immature RBC in the blood, these young cells retain some remnants of RNA and appear bluish when stained and laid out as a fine network called Reticulocytes. In normal conditions, the reticulocyte count is between 0.5 and 2 %. Reticulocytes over 2 % are seen in acute hemolytic anemia, massive hemorrhage, and in high altitude visitors.

When bone marrow is infiltrated, as in cancer metastasis and leukemia, Nucleated RBCs are visible in the blood and are called Erythroblasts. In times of stress,  the bone marrow also releases nucleated RBCs, e.g., hypoxemia, and removal of the spleen.

Inclusion Bodies:

Inclusion bodies are iron pigment, hemoglobin, remnants of DNA and RNA fragments in the red cell cytoplasm. Inclusion bodies are called Basophilic Striplings and Howell jolly bodies.

Basophilic stippling. These inclusion bodies represent defects in hemoglobin synthesis, appear as bluish stripes, widely distributed throughout the cell cytoplasm. Examples – Megaloblastic anemia, Post splenectomy and sideroblastic anemia.

Howell Jolly bodies. These bodies appear in the periphery of the cell as purple round dots when stained with Romanowsky stain due to the presence of fragments of DNA.

Siderotic granules. These granules are iron, which remains in hemoglobin and stains blue. Example: Sideroblastic anemia.

Parasites.

The malaria parasite belongs to the Plasmodium group. Several species of Plasmodium infect humans - mostly in people living in Sub-Saharan Africa and Southeastern Asia. As there are different species, several parasitic forms, like gametocytes, schizonts and trophozoites, are also seen in the blood of patients infected with malaria. Considerable experience is required to identify these intracellular malaria parasites.

Babesiosis. Babesia infection is seen in the New England States in summer months when tics are active. The parasites appear as ring forms, often in groups, and in heavy infestation rings in groups appear outside the red cells also.

Blood film in Babesiosis.

Important Points:

To a casual reader, this article may appear confusing and overlapping.

In clinical practice, however, the information is neatly and concisely presented. A few samples are presented.

Iron deficiency anemia.

Iron deficiency produces Hypochromic, Microcytic anemia. Besides a low hemoglobin, HCT (hematocrit), MCV (means corpuscular volume), MCH (mean corpuscular hemoglobin), Color index and Saturation Index are all low. RWD (red cell width distribution) is more than 15 %. This RWD finding is helpful to separate iron deficiency anemia from Thalassemia where RWD remains normal.

Macrocytic anemia.

A combination of low hemoglobin and low HCT in the presence of High MVH and MCHC (mean corpuscular hemoglobin concentration) is the rule.

Hemolytic anemia.

Intravascular hemolysis is a vast subject as such. Features of hemolytic anemia is the presence of normocytic and normochromic anemia with a normal RWD. If the hemolysis is less severe but recurrent then RWD rises above normal.

Sickle cell disease (SCD). In Benin, Senegal, and CAR (in sub-Saharan countries) death due to childhood malaria caused havoc. A mutation of the Beta Chain of the hemoglobin molecule at position 6 - substitution of amino acid glutamine to valine proved to be a lifesaver. That advantage led to a wide distribution of the mutated gene in the population. However, as people moved to the USA and Caribbean States from sub-Saharan Africa, that mutation has become a fatal mistake. In a low oxygen environment, the RBC of SCD patients changes from a disc to sickle form and obstructs blood flow in the capillaries and results in severe pain and loss of function. This results in death of cells, seen from the bone marrow to the brain.

                                Blood film in Sickle disease.

Thalassemia.

 A growing embryo in the mother's womb draws oxygen, due to the special characteristic of Fetal Hemoglobin. If fetal hemoglobin persists in postnatal life, due to a gene mutation, it is called Thalassemia. Thalassemic patients have anemia which has the following characteristics - Microcytic, hypochromic anemia with a high RBC count, normal MCV, normal RWD, high reticulocyte count, basophilic striplings and Target cells.

                                       Peripheral blood film in Thalassemia.

TTP (thrombotic thrombocytopenic purpura).

TTP is due to widespread platelet thrombosis in all organs producing an alarming medical situation. Hemolytic anemia due to mechanical break of RBC in their attempt to move forward in capillaries partially blocked by platelet thrombi, and a very low platelet count (10,000), the presence of schistocytes are characteristic features. Direct examination of blood film by hematologists can make a quick diagnosis. 

                             A blood slide in TTP, the helmet cells are marked by blue 

                                    circle.

Napoleon hat

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Eosinophil and Diseases associated with Eosinophils

 

                           Eosinophils and Diseases Associated with Eosinophils.

                                          PKGhatak, MD

Eosinophils are white blood cells that belong to granulocytes, other members of this group are Basophils and Neutrophils (also called polymorphs). The name, granulocyte, is derived from the presence of granules in the cell cytoplasm. The granules of eosinophils are coarse and turn red when stained with Eosin due to the presence of amino acids arginine and lysine in the protein, which reacts with Bromine in Eosin. The eosinophils are important Innate Immunocytes, involved in protecting the body from multicellular parasites, fungi, and some viruses, and are important determinants in certain diseases.

The easily identifiable feature of the eosinophils is their special characteristic, a Bilobed nucleus. 

Formation and distribution of Eosinophils.

The Hematopoietic stem cells of the bone marrow are the source of eosinophils; and in about 7 days the mature eosinophils leave the bone marrow. Most of them head for the thymus gland, spleen, lymph nodes, GI tract and the rest of the organs with the exception of the esophagus, ovaries, and uterus. Under normal health conditions, the eosinophils are not present in the Esophagus and Lungs and only a few eosinophils are present in the skin.

The Thymic Th2 cells initiate eosinophil production by secreting IL-5. (Interleukin-5).

Normal blood eosinophil count is 3 to 8 % and the total maximum count is 500 per microliter. In the peripheral blood, the eosinophils live about 1/2 days and in the tissues, they survive 8 days.

A total eosinophil count of 800 / microliter is abnormal and called hypereosinophilia, a count over 1,500 per microliter is called Hyper-eosinophilic syndrome.

There are very few conditions where the eosinophil blood counts are low. One is usually encountered when corticosteroid is administered. In Alcohol intoxication and Cushing's disease low eosinophil count are seen.

Normal functions of Eosinophil.

Eosinophils are immunocytes that act by releasing preformed substances, contained in the cytoplasmic granules. The pathophysiology of diseases is different from disease to disease. The substances carried in the granules can be grouped into – Oxygen radicals, Enzymes, Leukotrienes, Cytokines, Prostaglandins and Growth factors. In previous blogs, oxygen radicals, leukotrienes, prostaglandins and cytokines are discussed in detail and will not be repeated here.

Growth factors are TGF beta (tissue growth factor), VEGF beta (vascular endothelial growth factor), PDGE (platelet derived growth factor). In addition, the Eosinophils promote the development of post pubertal breasts, influence menstrual cycles and protect tissues from cancerous developments, prevent allograft rejection and help antigen presentation to T-Cells.

                               Hypereosinophilia

Herpesinophilia is seen in these conditions – Allergy, Asthma, Roundworm infestation of the gut, and Cutaneous larval migration like Filaria, Trichinosis, Cysticercosis. Eczema and Atrophic dermatitis, Chung-Strauss syndrome, Autoimmune diseases, Crohn's disease, Addison disease, Cancers of breasts, ovaries, and prostate. Leukemia and among the group of leukemias - Acute myelogenous leukemia (AML) and Eosinophilic leukemia are particularly striking. It is also seen in certain Fungal infections. Many prescribed medications produce allergic dermatitis and Penicillin leads the group; Penicillin may also produce Interstitial nephritis, which is characterized by the presence of eosinophils in the urine.

                                 Hypereosinophilic syndrome

When peripheral blood eosinophil count is persistently over 1,500 mcL for 6 months or longer and evidence of organ damage and allergy, parasitic infection and chromosomal abnormality are eliminated, the condition is called Hyper-eosinophilic syndrome (HES).

When the cause of high eosinophilia is known, the term Secondary Hypereosinophilic Syndrome is applied and many of the old HES are now classified under Secondary HES.

Chromosomal abnormality in hypereosinophilia.

The translocation of the gene between F1P1L1 and PDGFRA of the long arm of chromosome 4, at location 12 (4q12) produces a hybrid gene (F/P) which produces excess IL-5 causing rapid and excessive eosinophil production. Many other less prevalent Myeloid dysfunction due to chromosomal abnormalities are known, some examples are Chronic Eosinophilic Leukemia, Lymphatic HES, and Myeloproliferative HES.

Organs damaged by HES.

Esophagus, Stomach and intestine, Skin, Lungs and Heart. Multiple organs involved are the usual but only one organ or one system may be involved.

Clinical manifestation of HES.

Presentation and clinical features vary due to different organ /system involvement. Incidence in the USA is 0.3 to 6.0 per 100,000 population, including secondary EHS. General- Males are more affected by HES and ages between 20 and 50 are mostly affected. Systemic symptoms are fever, loss of weight, weakness. lethargy, pain in joints and muscles, and night sweats. Skin manifestations are itchy macular and nodular eruptions, angioedema and eczema. GI symptoms are heartburn, abdominal pain and diarrhea. Heart problems may mimic MI, endomyocardial necrosis, peripheral emboli and cardiomyopathy. Lung lesions resemble an attack of asthma, pulmonary infiltration and interstitial pneumonia and fibrosis. Unproductive cough. Hematological manifestations are many, chief among them are anemia, enlarged spleen and liver, and fibrosis of bone marrow. High serum B12 level. CNS manifestations are peripheral neuropathy, Transient ischemic attacks, strokes, and encephalopathy.

Diagnosis requires a complete blood count, serum B12 level, bone marrow biopsy and chromosome study.

Treatment of HES.

Intravenous corticosteroid is used to bring down the Eosinophil count rapidly, and Hydroxyurea is also used. Imatinib, a Tyrosine kinase inhibitor, is effective. Various other small molecules are available to suppress IL-5 production.

The prognosis is unfavorable without treatment. At present, with prompt treatment, the longevity on average is 80% in 5 years.

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Oral Ulcers

 

           Oral ulcers are also called Aphthous ulcers and also Canker sores.

                                     PKGhatak, MD

The word Aphthous is an adjective for the noun Aphtha. Aphtha is an old Greek word, the plural is Aphthae. Aphthae means Oral Ulcers due to any cause, that includes oral thrush and viral infections like foot and mouth disease (Picornavirus).

Oral ulcers develop in the mucous membrane (surface layer) of the gum, cheeks, roof of mouth and tongue. The ulcers have a white looking base surrounded by red inflamed borders and are painful.

Cause:

Any injury to the soft tissue of the mouth or tongue may start an ulcer. It is usually from a bite, ill fitting dentures, drinking hot drink or food, rough toothbrush, careless dental cleaning, vitamin B12, folic acid and iron deficiency, immune deficiency diseases or following chemotherapy and fungal (Candida) infection, commonly called thrush, and food allergy.

Diseases usually associated with oral ulcers:

Diabetes, Crohn's disease of the intestine, Celiac disease, Bechet's disease and Ulcerative colitis.

Other factors that favor oral ulcers are stress, hormonal changes, lack of sleep and infections.

Infection: The common virus infections are HIV and Herpes simplex; common bacteria are Staphylococcus, Actinomyces, and Helicobacter pylori. And common fungi are Candida albicans and Histoplasma capsulatum.

Course: 

Oral ulcers can be recurrent if the associated disease or conditions are not properly treated. Oral ulcers usually heal in 10 to 14 days.

When ulcers persist for more than 3 weeks, one of these conditions are responsible: - Fever, diarrhea, new ulcers appear before old ulcers heal, large size ulcers, ulcers on the outer lip surface are associated with oral ulcers.

Clinical types of oral ulcers:

There are two types - usual oral ulcers and herpetiform oral ulcers.

The usual ulcers are small to moderate sizes, oval to round shaped and have defined red edges. These ulcers heal without scarring.

Herpetiform oral ulcers are clusters of pinpoint ulcers, 10 to 100 ulcers and appear in groups. Later in the course, it may merge to become a large ulcer. These ulcers have a close resemblance to Dermatitis Herpetiformis of the skin. These lesions are not due to herpes virus infection.

Treatment:

Home recedes. Plenty of free advice is given over social media. Most of them include - frequent warm water salt gurgle several times a day; applying Back Tea bags directly over the ulcers - the tannin of the tea improves pain and accelerates the healing of ulcers. Similarly, powdered Alum (potassium ammonium sulfate), Baking soda, Orejel, Ambesol, honey, Milk of Magnesia and many other remedies are advocated.

Any food, having salt sprinkled over should be strictly avoided – salt crystal lodged in the ulcer crater is very painful and causes more tissue damage. Also, to be avoided are very hot food or drinks, spicy, difficult to chew food items and sour fruits and drinks.

Medication:

The most useful medicine is the Colchicine tablet. Use of Colchicine 0.5 to 2 mg a day for 2 days is enough to stop oral ulcers appearing and speeds up ulcer healing. At times Colchicine needs to be taken for longer periods of time, in reduced doses, to prevent a recurrence. Thalidomide 200 mg twice a day for 3 to 8 weeks is advised in immune related Aphthous ulcers. For bacterial infection, Minocycline or Tetracycline 250 mg in a cup of water(180ml) swishes around in the mouth and then spits out, three times a day for 3 to 5 days is also used.

At the same time, any underlying condition and illness should be adequately addressed.

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Gut Bacteria and Human Health

 

                                              Gut Bacteria and Human Health

                                                PKGhatak, MD

Every surface of the human body harbors microorganisms of various kinds, some are just parasites, others live in symbiosis. When the symbiotic relationship breaks down for one reason or another, the health of the body is adversely affected. Recent studies on Gut bacteria show these actions are both local and systemic, including immune mediated diseases. Dominant gut bacteria are Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia. However, Firmicutes and Bacteroides account for 90 % of the gut bacteria. About 10 to the power 10 number of bacteria are present per gram of feces in a normal state of health.

Firmicutes:

Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Enterococcus, Clostridium, and Ruminicoccus.

Firmicutes bacteria produce fermentation of undigested carbohydrates and cellulose and produce intestinal gases and Lactic acid. It releases antioxidants and micronutrients. The growth of colonies of Firmicutes in the colon plays an important symbiotic relationship. Humans provide food for the bacteria and Firmicutes in return supply micronutrients, suppress the growth of disease causing bacteria, namely enteric staph, anaerobic bacteria and Clostridium difficile.

Bacteroidetes:

Bacteroidetes are gram negative pleomorphic rods, non-spore forming, anaerobes and are both helpful bacteria of the gut but also may cause anaerobic infection under certain conditions. In a normal symbiotic existence, the Bacteroidetes break down undigested simple sugar, complex sugar, fat and protein in the gut and support other gut bacteria and also supply the human hosts with vitamins and micronutrients. A diet rich in oats, onion, ginger, flax seeds, and apples is a good food source for the Bacteroidetes.

The ratio of 20: 620 between Firmicutes and Bacteroidetes indicates a normal ratio and indicates good health of the individual. When the ratio tilts toward Firmicutes, it is generally associated with increased calorie absorption from the gut, insulin resistance and obesity, indicating a chronic inflammatory environment leading to cardiovascular disease propensity.

Immunoglobulin A.

Peyer's patches of the small intestine and B lymphocytes in the lamina propria of the colon produce IgA antibodies. Gut bacteria are in a seesaw relationship with gut IgA.  Bacterial antigen stimulates IgA antibody production and antibodies keep bacterial growth in check.

How symbiotic relationships develop.

The foreign antigen detection cells are Dendritic cells. In the gut, the dendritic cells are present in a loose connective tissue layer just beneath the gut epithelium and are in close proximity with the gut bacterial colonies. This constant contact has produced a state of "Inflammation Anergy" and the dendritic cells do not collect bacterial antigens and as a result, the macrophages do not produce pro- inflammatory cytokines.                 

IgA associated diseases:

Though IgA antibody production is highest among all Immunoglobulins, very little IgA antibody enters the blood; IgA is almost exclusively used up in the gut. In diseases due to IgA deposits in tissues, the IgA can be detected by Immunohistochemical staining of tissues.

COVID-19. The covid virus infects the gut mucosa, and the IgA antibodies try to eliminate the virus by its neutralizing action, however, in a small number of cases the elimination is only partial and COVID-19 virus is detected in feces for a long time.

IgA Nephropathy (IgA N).  It used to be known as Berger's disease.

IgA Nephropathy is the most common type of Nephropathy in Asia and also in the world.

It is postulated that the respiratory tract bacteria produce Degalactosylation of IgA molecule. This degalactosyzed IgA (dIgA) becomes an antigen and antibodies are produced. Then antibodies and dIgA combine and this Antigen + Antibody complex is deposited in the extracellular matrix of the Glomeruli of the kidney leading to IgA Nephropathy. The previously held theory was that aberrant glycosylation of IgA leads to polymerization of IgA and because of the complex's large size, these complexes are deposited in the mesangium of glomeruli. Inflammation starts as a result and glomerulonephritis progresses to membranous glomerulonephritis with crescent formation.

Henoch Schönlein purpura.

Purpuric eruptions develop following a URI. The purpura is mostly seen in the legs, buttocks and sometimes in the hands, face and trunk. The purpura is more abundant along with the pressure points like the sock line and the waistband. Purpura is palpable and does not fade away on pressure. Children between 2 and 6 are mostly affected. Male children and white and Asian children are more vulnerable to HS purpura. The underlying pathology is a vasculitis of small vessels of the skin, mucous membrane and joints. Lesions in the mouth and arthritis may develop. GI symptoms are common and some also develop IgA nephropathy.

Skin lesions.

Dermatitis herpetiformis.

Clusters of raised red, intensely itchy lesions develop on elbows, knees, buttocks, occasionally on arms and on the scalp. The lesions are intensely itchy. Often blisters develop from scratching and scars form when they are opened up from scratching.

People of the age group 30 to 40 of European heritage develop recurrent lesions. Oral and GI lesions also occur. Aphthous ulcers in the mouth and pits and fissures on the enamel of teeth may appear, GI manifestations are bloating, cramps and diarrhea.

Cause.

IgA antibodies develop against the skin epidermal transglutaminase. It is the skin manifestation of Gluten enteropathy from gluten sensitivity.

Diagnosis.

Demonstration of IgA deposition in the upper layers of the dermis by immunofluorescence.

Dysmorphic Epidermolysis Bullosa.

IgA deposition at the junction of the basal layer of the epidermis and papillary cells of dermal held by collagen fibrils are damaged by the process. The epidermis is easily lifted off from the dermis with minor trauma. Blister formation and secondary infections are common. Epidermolysis Bullosa is an inherited disease. It is inherited by autosomal recessive and autosomal dominant modes and multiple gene mutations are present.

There are several clinical types based on clinical presentation and the associated involvement of other systems. GI, GU, Respiratory, ENT may variously be involved.  It may be present at birth or at anytime later in life. It is a serious disease. There are serious complications. even when patients initially respond to treatment. Esophageal stricture and cancer are usual.  Diagnosis is made by immunofluorescence staining of the biopsy tissues. The prognosis is variable but not good in general.

Summary.

IgA is the principal immunoglobulin in keeping the GI tract and other mucous membranes of hollow organs free of pathogens. Because of constant contact with bacteria, some of the bacterial degradation products/secretory enzymes become antigenic and antibodies are produced. Antibodies can react with normal tissues like nerve cells, GI cells, etc. This hypothesis has generated a new look into the pathogenesis of Multiple sclerosis, Parkinson's disease, etc. In the future, more and more laboratory confirmations will be available.

Lately, many attempts have been made worldwide to limit the use of antibiotics in supposed bacterial infections or recurrence, which are in fact infections from viruses. Also cut down the duration of antibiotics use from 15 to 5 days for an infection, like walking pneumonia and many other minor ailments. This practice will result in the return of a healthy symbiotic relationship between the gut bacteria and humans.

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Osteoarthritis

 

                                                          Osteoarthritis

                                                PKGhatak, MD

Osteoarthritis is a degenerative disease followed by inflammatory disease of the joints.

In the initial stage of Osteoarthritis (OA), the wear and tear produce damage to the cartilage covering the ends of the bones forming a joint. When cartilage is destroyed, the bones are exposed and rub against each other, causing pain. Subsequently, the bones and joint capsule also undergo inflammatory changes. Osteoarthritis (OA) is distinct from Rheumatoid Arthritis (RA) where inflammation primarily is in the synovial membrane of the joints and then spreads to bones and the rest of the joint structures. RA is an autoimmune disease and affects the lungs and other collagen vascular structures of organs.

OA is a disease of the elderly. Young people also develop OA from sports injuries, in addition, OA develops secondary to other diseases and a few hereditary diseases which damage the cartilage.

Cartilage.

The ends of bones forming a joint are covered by a layer of cartilage called Articular cartilage. Articular cartilage has a unique ability to withstand high loads with little damage. Cartilage is connective tissue and provides structural support like bone. In fact, in the animal kingdom, the development of the backbone, the cartilaginous vertebral column appeared first, then came the bony vertebrae, even then, currently the oceans are full of cartilaginous fishes, sharks for example.

The cartilage is composed of a dense extracellular matrix. In the matrix a few sparsely distributed cells called Chondrocytes are present. The extracellular matrix is composed of water, collagen(protein), proteoglycans (protein+carbohydrate) and other glycoproteins. These structural components make cartilage retain water and provide a cushion and absorb the body weight and pressure during joint movements.

Blood supply to cartilage is absent, this results in poor healing properties of cartilage. It is devoid of nerves and so insensitive to pain.

The part of the bone next to the cartilage layer is known as the subchondral plate and is very vascular. Nutrition to articular cartilage is provided by synovial fluid.

Commonly affected Joints in OA.

OA can start in any joint, but the joints commonly affected joints are Knee, Lumbosacral and Cervical Spine, Hips and thumb.

The thumb and distal finger joints are commonly affected in elderly females. Knee, Lumbosacral, Cervical Vertebrae and Hip joints are equally affected in both sexes. OA of shoulders and fingers are generally spared, unless overused, for example, manual laborers and coal miners.

The middle joints of the fingers are typically affected in RA. This is an important distinction between the RA and OA. RA patients show associated systemic symptoms and x-ray evidence of erosion of bone ends of the finger joints and elevated acute phase reactants in the blood.

Risk factors to OA.

Injury, obesity, manual workers, sports injuries, diabetes, in addition, OA develops secondary to several diseases. Closely resembles but distinct from OA are Gout, Pseudo gout, and Peripheral sensory neuropathic arthritis.

Secondary causes of OA.

Metabolic defects of cartilages:  Ochronotic arthropathy, Alkaptonuria, chondrocalcinosis, or pseudo gout.

Connective tissue metabolism:    Hurler syndrome, Morquio disease, Marfan syndrome, Poly-epiphyseal dyslexia.

Congenital bone defects:   Scoliosis, Spina bifida, Club foot, Leg-Parthese disease.

Hereditary gene mutation:    Hemochromatosis. Sickle Cell Anemia.

Blood clotting abnormality:   Hemophilia.

Autoimmune disease:   RA, Psoriatic arthritis. Crohn's disease, Ulcerative colitis,

Leukocyte Antigen gene mutation:    Ankylosing spondylitis due to inherited HLA-B27 gene.

Endocrine disease:    Acromegaly, Cretinism, Dwarfism, Hypothyroidism, Menopause.

Neurogenic:   Muscular dystrophies. Syringomyelia. Charcot arthropathy. Reflex sympathetic dystrophy.

Vascular:    Aseptic necrosis of hips, Caisson disease

Symptoms of OA.

All different types of arthritis produce similar symptoms like pain, swelling, muscle stiffness, and limitation of range of motion. OA is a local disease and produces very few systemic effects. OA of the vertebral column has some unique features. In cervical spine OA - the wry neck may start even before the radiological evidence of OA. Thorns like outgrowths of bone spicules produce sharp jabbing pain. OA of facet joints limits turning of head and torso side to side and specially backward. Stenosis of the cervical spine can produce spastic paralysis of the legs. In the lumbar area, OA produces muscle spasms. Lumbar stenosis can interfere with bladder and bowel functions, in addition to muscle weakness of lower legs, often seen as foot drop and marked limitation of climbing stairs.

Diagnosis.

History and clinical examination are sufficient to make a diagnosis of OA. There is no blood test to confirm OA, however, blood tests are done to exclude other forms of arthritis. X-rays are an essential part of diagnosis showing loss of joint space, subchondral bone sclerosis and small outgrowths from the ends of bones in OA.

In the weight bearing joints, like knees, an x-ray is used to stratify OA into early, intermediate and advanced stages. In the advanced stage of OA knee, surgical replacement of the knee is advocated.

Medical treatment of OA.

There is no cure for OA. The non-steroidal anti-inflammatory drugs are the mainstay of the treatment of OA. These drugs produce relief of pain and limit bone inflammation.

In addition to medication, physical therapy, daily exercise and weight reduction, where applicable, are advised. When pain is acute, rest of that joint is essential till the pain is tolerable then physiotherapy is helpful. Use of other anti-inflammatory drugs, narcotics and muscle relaxants are discouraged.

In some European countries, intra-articular lubricant, a visco-supplementation containing Hyaluronic acid, is injected into the knee to lessen friction and pain. Use of it in the USA is generally not recommended because the beneficial effects last only a few months, if at all. and a chance of infections in repeated injections is a real possibility.

Surgical Treatment.

In advanced knee OA, joint emplacement is commonly advised. Corrective surgery of various kinds is done for cervical and lumber vertebral stenosis.

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Long Covid

                                                          Long Covid

                                              PKGhatak, MD

Long covid is a new disease. The precise definition of Long covid is lacking. A cornucopia of symptoms lasting for weeks to 18 months or more experienced by people who had a covid illness and recovered are thought to be the sequel to covid infection and named Long Covid.

There is no reliable way to determine the percentage of the world population that developed Covid-19. In January 2022, one estimated the rate was 57 %, another source reported it was over 75% in January 2022 (6+ billion out of 8 billion).

The vast majority of covid-19 illness produces symptoms that are very similar to the Common cold and symptoms last only 3 to 5 days. The number of seriously ill patients worldwide will remain unknown because the variable of public health standards prevails in the vast number of developing countries and local politics prevented notification.

Who developed Long Covid.

The wide spectrum of people with mild symptoms or no symptoms but who had a positive PCR test to more seriously ill patients with a variety of symptoms are considered to have Long Covid. Even those who were fully vaccinated and boosted, contact with the virus also reports long lasting symptoms. It appears severity of symptoms is not a factor in acquiring Long Covid. It is estimated that 35 to 20 % of patients who recovered from covid-19 infection developed Long Covid.

What are the symptoms of Long Covid.

General. Loss of weight. Lethargy. Palpitations, Pain in joints, skin rashes,

Respiratory. Unproductive cough, shortness of breath, worsening existing asthma and COPD

Neurological. Loss of smell or taste, both, weakness, numbness, lightheartedness, brain fog (difficulty in thinking and concentration), disturbed sleep,

Psychological. Depressive mood, lack of energy, pain and tenderness in many areas of the body, anxiety.

GI. Lack of appetite, intermittent diarrhea, vague abdominal pain, bloating sensation.

Cardiac. Variable BP and sudden surge of BP, palpitation, chest pain.

Urinary. Dysuria and frequency.

Metabolic/ Hormonal. Out of control blood sugar, thyroid function, menopausal symptoms, lack of libido. 

Worsening of symptoms that remained after recovering from severe COVID-19, like heart failure, asthma, paralysis of limbs, etc. Weakness and brain fog are mostly responsible for absenteeism at the workplace in the long covid.

Many researchers noted that these symptoms are not unlike symptoms of chronic fatigue syndrome, also known as Myalgic encephalomyelitis and PTSD (post-traumatic stress syndrome)

What are the reason/ reasons for Long Covid.

No one reason stands out among several put forward so far. In general, people who are immunodeficient are more prone to Long Covid. It is theorized that immunocytes in these groups fail to clear the virus but the virus is weakened and continues to infect new tissues. This model fits with the observation that patients treated with a cocktail of antibodies during the early phase of infection have higher instances of Long Covid.

Another interesting theory is the virus takes sanctuary within the immunocytes and waits for an opportunity to re-emerge like the HIV/AIDS virus and Paxlovid breakthrough infection. Recent discovery points to Langerhans cells of the skin, which engulf the virus but fail to digest because the virus directs anti-enzyme to neutralize the digestive enzymes of the Langerhans cells.

Long covid has emerged as a major disabling illness putting a drag on the economy and untold suffering for people eager to return to work but unable to.

Initially, it appeared booster covid shots were beneficial in terms of lessening the symptoms and the length of the period of disability. But subsequent studies failed to find any benefit of the booster shots.

Covid -19 pandemic caused havoc to humanity. It continues to evolve as a major health risk factor worldwide. One reliable source report 6 million deaths from covid-19, others think that number is way short of the actual number, citing India as an example. The WHO reports one million covid deaths since January 2022 alone.

Sooner or later a plateau will be reached in the rate of new covid-19 infections which can be managed like Influenza outbreaks with vaccines given every year. Antiviral drugs against the covid-19 virus may prove to be as elusive as HIV/AIDS virus. And hopefully, the Long Covid will be just another cause of Chronic Fatigue Syndrome or Myalgic Encephalomyelitis for those who prefer Latin names.

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