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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Bell's Palsy

                                                                        Bell's Palsy.

                                                              PKGhatak, MD

Sudden onset of paralysis of one half of the entire face is called Bell's palsy. In medical terms, it is a lower motor neuron paralysis of the facial muscles of one side. Bell is Sir Charles Bell of Scotland (1774-1842). He was a Neuroanatomist cum surgeon. He gained first-hand knowledge of facial injuries while working as a surgeon in the Battle of Waterloo (1815).

The term “Palsy” is derived from the Anglo-French word “Palseie”. The Greek word “Paralysis” means loosening, it is derived from the verb “Paralysia” meaning to disable/ enfeeble.

Although Sir Charles Bell was the first to provide the anatomic basis for the condition that bears his name, in recent years researchers have shown that other European physicians provided earlier clinical descriptions of peripheral cranial nerve 7 palsy. History of facial distortion by Greek, Roman, and Persian physicians, culminating in Razi's detailed description in al-Hawi (9^th century CE). Razi distinguished facial muscle spasm from paralysis, distinguished central from peripheral lesions, gave the earliest description of loss of forehead wrinkling, and gave the earliest known description of bilateral facial palsy. In doing so, he accurately described the clinical hallmarks of a condition that we recognize as Bell palsy.

Dr. Bell, of Bell's palsy fame, had suffered a right sided facial paralysis of his own before he became famous.

A question:

Mona Lisa. Whoever has seen the world famous painting of Mona Lisa by Leonardo da Vinci must have pondered what that smile is all about. At a conference in Vienna, a group of researchers said Mona Lisa had right facial paralysis during her pregnancy and recovered after childbirth.

Anatomy of motor nerve of the face.

The above diagram is an outline of the 7^th nerve motor nerve supply to facial muscles. The pyramidal cortex sends signals to the upper division nucleus of both 7^th cranial nerve motor nuclei. (Facial nerve). The lower division of 7^th nerve motor nucleus, on the other hand, receives signals from one side only (contralateral side). In a stroke due to pyramidal cortex disease, only contralateral side of the face is paralyzed and muscles of forehead remain functional.

In Bell's palsy, the entire facial muscles, including the forehead muscles, are paralyzed.

Common causes of Bell's Palsy.

Chill wind blowing against the face in a long drive.

Herpes zoster. Herpes simplex. Epstein-Barr and COVID-19 virus infection.

Lyme disease from spirochete infection.

Acoustic neuroma (tumor of 7^th nerve fibers in the ear), Schwannoma (cells that make myelin) and cholesteatoma.

Injury to the Facial nerve.

During surgery of the parotid gland, a Knife wound behind the ear. Fracture of the base of skull. Nerve block during dental procedures.

Pregnancy and diabetes mellitus.

Critical areas of the path, the Facial nerve, where disease is likely to produce Bell's palsy.

1. Narrow canal inside the Temporal bone. 

2. The neck of the mandible.

 3.Parotid salivary gland.

Causes of paralysis of the Lower part of the face only.

A.  Strokes from blocked blood supply to the mid brain.

B. Blood clot emboli originate from heart valves, heart chambers, or atrium in atrial fibrillation.

C. Infectious vegetation from heart valve or artificial valve disease.

D. Intracerebral bleeding from use of anticoagulants.

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Dizziness and Vertigo.

                                                          Dizziness and Vertigo

                                                    PKGhatak, MD

Dizziness is not an uncommon symptom, specially in the elderly. Patients describe the symptoms in various ways - lightheartedness, feeling unsteady while walking, a sense of not being able to keep an upright posture while trying to get up from a bed or a chair, head spinning, about to faint and like.

Vertigo symptoms are related to a false sensation of motion of the surroundings.  Generally, head movements precipitate an attack of vertigo. Fear of falling on the ground from a bed or an upright position is often associated with nausea and jerky movements of the eyes.

The distinction between dizziness and vertigo is important from diagnostic and treatment points of view. But often one term is used for the other. The task falls on the physician to get a clear history from the patient and only then proceed with the investigation.

What causes dizziness:

Many medical conditions may cause dizziness, chief among them are postural hypotension, irregular cardiac rhythm, disturbed blood flow to the hindbrain (lower posterior part of the brain) and low blood sugar.

Other conditions less commonly associated with dizziness are alcohol intoxication, antidepressant drugs, migraine, and carbon monoxide poisoning.

What causes vertigo:

Vertigo is due to abnormal signals fed to the brain from the semicircular canals of the inner ear called the vestibule.

Each vestibule contains 3 semicircular canals, positioned at 90 degrees to each other. The canals are filled with a viscous fluid called endolymph, floating on the endolymph there are tiny pebble like structures called otoconia, connected with the vestibular division of the 8^th cranial nerve. Any movement of the head displaces the otoconia and initiate signals from both ears and the signals are reciprocal to each other. The brain integrates these signals and accurately calculates the coordinates of the head position in relation to the horizon.

Diseases affecting the inner ear are the cause of Vertigo.

Common conditions causing vertigo:

Viral infection of the balance organ is commonly known as Labyrinthitis, motion sickness due to overstimulation of the brain from the constant change of head position – a common experience of passengers on a boat in a choppy sea, benign paroxysmal positional vertigo, and head injury. Other conditions are:-

   Neuronitis, Meniere's disease, Tumors like meningioma pressing on the hindbrain, Vestibular migraine, and Brain cancers. Cerebral strokes and Multiple sclerosis.

The medication can also cause Vertigo, a few examples are certain antibiotics, water pills, cancer drugs, and aspirin in heavy doses.

Meniere's disease:

A combination of tinnitus (low volume high pitched noise like the chirping of crickets), some loss of hearing, and vertigo is known as Meniere's disease. The reason for this disease is not known. Symptoms are generally episodic but tend to be recurrent. After each attack, the hearing loss increases.

Benign Paroxysmal Positional Vertigo (BPPV):

Sudden head movement or turning the head to a certain position causes BPPV. It is very disturbing to the patients but it causes no permanent harm to the body. The sensation of the horizon tilting up and down causes the patient to grab whatever they can to avoid falling to the ground. The condition is self-limited but may be prolonged. A certain maneuver of the head position can stop vertigo and the patient can learn the technique and can self-treat. 

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Sudden Death

 

                                                                  Sudden Death

                                                        PKGhatak, MD

In human experience, an unexpected sudden death must be the most devastating and sad event for the family members.

When death finally comes to a person with an incurable chronic illness, some may say “Good is merciful and he/she is in peace. But what one can say to a mother when a child is killed in a school by gunshot or a newborn dies from sudden infant death syndrome. Is the same God merciful here also?

In the USA, about 200,000 deaths are happening every year from unintentional causes, chief among them are drug overdose, motor vehicle accidents, falls, and drowning. Deaths from gun violence and suicide are 45,000 per year for each. The remaining deaths are from accidents. heart attacks and undetermined causes. The deaths from undetermined causes pose another dimension to the suffering for the family – did they miss something to spot in time and take proper action to prevent death.

Sudden Infant Death Syndrome.

Healthy infants below 1 year. old people were dying suddenly for no apparent reason. This was a major concern of health professionals and in 1969, 'Sudden Infant Deaths Syndrome (SIDS)' was coined to study these cases and find the cause and prevent such deaths. In the USA in the year 2020, 3,400 babies below one year of age, died suddenly. Of these, about 40 % were SIDS, 30 % were accidental suffocation and 25% were unknown causes. The present incidence of SIDS is about 96 deaths per 100,000 live births.

Various theories were put forward to explain the cause but most of them were not substantiated by scientific studies. Placing babies on their stomachs in the crib was the main common factor. Since this practice was abandoned, the incidence fell and held steady.

Cardiac Arrest:

'The heart stops pumping blood' is the simplest way to define the term cardiac arrest. As the heart stops so also does the circulation of blood and within a few minutes living cells begin to die. If resuscitation can be started early and properly the heart can be revived within several minutes.

Mechanism of cardiac arrest:

Lack of oxygen

Oxygen supply to the heart muscles depends on patent coronary arteries. If a coronary artery is blocked by a rupture of an atheromatous plaque, blood cannot go past the blocked area, and lack of oxygen makes heart muscle hyperexcitable, and abnormal ventricular contraction begins. If the situation does not reverse, then ventricular tachycardia (VT) and ventricular fibrillation (VF) precipitate. In ventricular fibrillation, blood virtually remains in one place, and no pulse is generated. This is the usual cause of death.

Ventricular Tachycardia (VT):

In ventricular tachycardia, the ventricles contract 120 to 180 times a minute. At this rate, ventricular chambers have only 0.25 seconds to 0.125 seconds to fill (normal ventricular filling time is 0.5 sec). This results in a precipitous drop in cardiac output and blood pressure, and the patient goes into shock.

In right coronary obstruction, the blood supply to the Sinus Node, the normal heart pacemaker of the heart, is cut off. After the right coronary artery is blocked, the heart rate slows (sinus bradycardia) and A-V(atrioventricular) nodal rhythm and various forms of heart blocks and complete heart block may develop. Complete heart block generally produces convulsions and loss of consciousness. It can also produce ventricular fibrillation, shock and death.

Uncommon but significant other causes of VF.

Hypokalemia, hypocalcemia and hypomagnesemia are known to produce VF.  Special importance in clinical practice is the condition called prolongation of Q-T interval which can precipitate a fatal multifocal VT. Prolonged Q-T interval results in enhanced automaticity, which most commonly originates in the right ventriclar conductive tissue. At the cellular level, the VT is caused by electrical re-entry. Myocardial scarring from the previous heart attack increases the likelihood of electrical reentrant circuits.

VT from a prolonged Q-T interval is called "Torsade de Pointes(meaning twisting around a point). It is an uncommon and distinctive form of polymorphic VT, characterized by a gradual change in the amplitude and twisting of QRS complexes around the isoelectric line.

Determination of Q-T interval.

[The linear regression model yielded a correction formula (for a reference RR interval of 1 second): QTLC = QT + 0.154 (1-RR) that applies to men and women. This equation corrects QT more reliably than Bazett's formula, which overcorrects the QT interval at fast heart rates and undercorrects it at low heart rates. Lower and upper limits of normal QT values concerning RR were generated.]

The normal Q-T interval in men is 350 to 450 milliseconds and in females is 360 to 460 milliseconds. 

Many medications can prolong Q-T interval. A short list of drugs is:

A cardiac drug - Quinidine. 

Antihistamine – Astemizole, Diphenhydramine.

Antibiotics – Macrolide antibiotics, Quinoline group of antibiotics.

Antihypertensive – Nicardipine.

Antidepressants – Serotonin receptor blockers, Amitriptyline, Lithium

Anti-malarial – Chloroquine.

Anti-Fungal – Ranolazine

Anti-cancer – Tamoxifen

Anti-convulsant – Felbamate, Fosphenytoin.

Bronchodilators – Albuterol. Salmeterol.

CNS stimulants – Amphetamine.

Muscle relaxants – Tizanidine.

Many people die in their sleep who took a cold or allergy medication before going to bed. Torsade de Pointes is likely the main reason for such deaths. 

Incidence of heart attacks and fatality in the USA:

In 2018, about 30 million incidences of heart related conditions were recorded. The common heart conditions are angina, heart attacks, cardiac arrest and heart failure.  And 650,000 deaths are due to heart conditions per year. The cost of treating heart related diseases, including loss of wages, totaled about $ 260 billion each year in the US.

 Incidence of Out of Hospital Cardiac Arrest:

On average 360,000 incidents per year are recorded in the USA alone, which is about 1000/day. 80% of cardiac arrests happen at home, 15 % in public places, and 10% in nursing homes. 2 incidences of cardiac arrest happen out of 10 million athletic events per year. The recurrent cardiac arrest rate is 20%. Males suffer much more heart attacks and the number in females increases sharply after menopause. Males in 50 -59 yr. have the highest rate - 27 % of heart attack, followed by 25 % in 60 -69 yr. age group, below 50 years. of age is 18 %. Looking at this in another way - the incidence of first heart attack per 100, 000 population in the 40 - 49 years age group is 98. After the first heart attack, life expectancy is cut short by 18 years.

Opioid Overdose:

Opium and its semisynthetic derivatives act as powerful inhibitors in the respiratory centers (located in the hindbrain). Opium causes a diminution of the respiratory drive and depth of breathing. Accumulated Carbon Dioxide (CO2) and Acid blood pH (pH less than 7.4) are powerful respiratory stimulants but fail to overcome opioids' depressive effect. The person who overdosed slips into a coma and dies. These deaths occur at night during sleep and are not noticed by family members or friends.

Strangulation, Aspiration of solids in the major airway:

Accidental swallowing of a solid object or a large piece of meat completely blocks the airway above the larynx. The person struggles when the airway is blocked, but he/she is unable to clear the throat, often because of associated alcohol intoxication, which is commonly seen in adults. Lack of oxygen produces ventricular arrhythmia and death due to ventricular fibrillation.

Road Accident and Gunshot Wound:

Loss of blood is the primary cause of shock and death. In some cases, direct injury to the heart results in cardiac arrest.

Pulmonary Embolism and Ruptured Arterial Aneurysm:

Massive pulmonary embolism very rarely happens in an otherwise healthy individual. Medical conditions change certain coagulation proteins favoring intravascular clotting. To name a few conditions - myeloma, polycythemia, malignancy and leg vein thrombosis. Massive pulmonary embolism prevents blood from reaching the gas exchange portion of the lung (alveoli). Lack of oxygen produces bluish discoloration of the face, lips and tongue (central cyanosis), the breathing rate increases to 30 -35/ minute, BP falls and the patient goes into shock. High flow oxygen fails to correct low oxygen in the blood. Death from massive pulmonary emboli usually happens within hours.

Aortic and abdominal aneurism, in the early stages, may remain silent. During a routine physical examination and also chest x-ray can detect silent aneurysms. When an undetected aneurysm ruptures no time should be lost in order to stop internal bleeding. Otherwise, it will be fatal.

The unexpected sudden death of a middle aged family man with young children at home brings massive grief to the family members and many problems arise from unfinished work left behind by the departed. Even with expert help, no one can adequately prepare and leave things in the proper places. Humans have yet to discover what is waiting for him/her tomorrow.

 Written in Memoriam of Shomik Roy, my nephew. 1971 - 2022.

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Epilepsy

                                                                 Epilepsy

                                                  PKGhatak, MD

Epilepsy is abnormal electrical activity of the brain producing alteration of muscle tone or convulsions, and changes in behavior and consciousness of an individual. Any one of these symptoms or various combinations of symptoms are the features of epilepsy. Convulsions are commonly known as seizures. Seizures and epilepsy are often used interchangeably, but strictly speaking, when two or more seizures occur at least 24 hours apart, then it is called epilepsy.

Previously seizures were classified by various names and at one time 30 to 40 different names were used. At present, there are two main groups of seizures

1. Primary generalized seizures. 2. Partial or limited seizures.

1. Primary generalized seizures.  Previously this was called Grand Mal seizures. In primary generalized seizures, abnormal electrical activities originate from both sides of the brain.

 2. Partial limited seizures originate from one limited area of the brain and remain localized to one half of the brain.

Commonly used terms for seizures are:

1. Simple focal. 2. Complex focal. 3. Absence of seizures. 4. Atonic seizures. 5. Tonic-Clonic seizures. 6. Myoclonic seizures.

This classification is not hard and fast because one type of seizure may change to another, for example, a simple focal seizure may turn into a complex focal, or a tonic seizure turns into a tonic-clonic seizure.

A list of medical conditions that may cause seizures.

1. Alcohol withdrawal.

2. Hypoglycemia (very low blood sugar)

3. Cerebral anoxia

4. Strokes

5. Certain medications

6. Encephalitis and meningitis

7. Sleep deprivation

8. Sustained exposure to flashing bright light

9. High fever and teething in children

10. Drug abuse, usually cocaine and amphetamine.

11. A-V malformation of the brain

12. Eclampsia of pregnancy

13. Hypothyroidism

14. Electrolyte imbalance.

15. Brain tumors.

Common causes of seizures according to the age of patients.

In young children. Brain injury during birth, Congenital abnormalities of the brain, Fever.

Young adults. Traumatic brain injury. Surgical scar of the brain, Drug abuse.

Adults. Brain injury and tumors.

Elderly. Strokes, Alzheimer's disease, Hypoglycemia, electrolyte imbalance.

CNS infection is an additional cause for all groups.

Clinical Presentation.

1. Absence or Petit Mal seizure.

It is commonly seen in children between 4 and 14 years of age. Sudden onset of a blank look in the middle of a conversation, smacking of lips and chewing motion. The seizures generally last only 10 to 15 seconds. The cortico-thalamic tract propagates abnormal impulses. Inheritance of GABRG2, GABRG3 and CACN gene mutations produces malfunction of energy dependent T calcium channels, which produce hyperexcitable brain cells and initiate seizures. This condition generally resolves at puberty.

2. Atonic seizure or Drop Attack. Sudden loss of muscle tone or strength causes the patient to fall on the ground, attacks lasting 15 to 30 seconds. The patients retain consciousness during the attack. The cause of the origin of this seizure is unknown.

3. Simple Local and Complex Seizures.

In a simple local seizure, it is also called an Aura. The seizures are either a movement abnormality, sensory or autonomic or psychological abnormal experiences. Muscle tightening, rolling eyeballs head movements are some of the common movement abnormalities. Numbness or crawling of insects under the skin is often mentioned by the patients. Hallucination involving hearing or vision is common. The patients may experience unfounded fear or anxiety. The patients are fully cognizant of abnormal muscle movements or sensory experiences and can fully recall incidents.

Complex seizures are like Simple Local seizures but the patients are not aware of the seizures during the attack or do not remember anything after the seizures stop. This seizure is also known as Temporal lobe epilepsy.

    4. Tonic-Clonic seizures.

Violent muscle contractions and fall on the ground and complete loss of consciousness, often a shrill cry is heard due to laryngeal muscle contractions, air entry to trachea may be prevented producing cyanosis, foaming of the mouth, chattering of teeth or forceful mouth closure, involuntary urination, arching backward due to back muscle contractions are some of the features of grand mal seizures. This seizure, the general public understands to be epilepsy. The seizures last several minutes and when exceeding 5 minutes, this becomes an emergency known as Status Epilepticus.

   5. Myoclonic seizure.

The muscle contractions are tonic-clonic but limited to a small number of muscles. Convulsions last only 2 to 3 seconds and the patient remains conscious.

Diagnosis of seizures.

An eyewitness account of a tonic-clonic attack is as good as a diagnosis that can be made on clinical grounds only to be confirmed by an Electroencephalogram (EEG; see footnote) and MRI. In many cases, photic stimulation is used for additional EEG recording. Other provocation tests may be required for localizing.

EEG in a normal person shows wave patterns classified on the frequency of waves per second. Normal waves are Alpha - 8 to 13 waves per second, Beta -13 per second, Theta - 4 to 7 per second, Delta -up to 4 per second, Gamma - 25 to 100 per second. The waves are not synchronized.

EEG in epilepsy shows synchronized spikes waves, each wave lasting 1/12 second, followed by delta waves.

MRI in epilepsy.  MRI shows structural abnormalities of the brain. In epilepsy, the MRI should be normal unless the epilepsy is due to other medical conditions deforming the brain. Other forms of MRI, like functional MRI, are useful for research purposes. 

In suspected CNS infection, spinal fluid examination and proper cultures and immunological studies are needed.

Treatment.

Status Epilepticus is an emergency. After securing the patient on a stable surface, the airway is protected and supplemental oxygen is administered.

IV Lorazepam 2 mg is given slowly, repeated after 1 minute in steps till the seizure stops or the maximum dose of 0.1 mg/Kg is given. If after 30 minutes the seizure continues, then Levetiracetam 20 mg IV is given. Alternatively, Valproic acid 40 mg IV may be used. If seizures continue then the Anesthesiology team is called and general anesthesia is induced to control convulsions.

Oral medication.

There are several effective oral medications available. The choice depends on the type of seizure, age and sex of the patients. In pregnancy and breastfeeding, special attention is required.

Commonly used oral drugs are Levetiracetam, Phenytoin, Valproic acid, Lamotrigine, Topiramate, Phenobarbital, Zonisamide,  Carbamazepine and Gabapentin.

In most cases one drug is not enough to control seizures, two or more drugs are required. Levetiracetam is well tolerated and has few side effects. It works differently from other anticonvulsant drugs. Levetiracetam combines with SV2 protein and prevents the release of neurotransmitter that is responsible for the epileptic electric discharge.

Duration of therapy.

Oral medications are continuously used for months and unless patients have no seizures for two consecutive years, the drugs are not stopped. In most patients, drugs are required for life. Therapeutic blood levels of many drugs are available and should be utilized to adjust the dosage. Phenytoin therapeutic level is 10 to 20 mcg/ml. Care should be taken in adding an additional dose of phenytoin at the higher range of therapeutic level because a small addition may push blood levels well past the normal range.

Surgery.

Removal of a single scar of the brain provides the best surgical outcome in uncontrollable seizures. The use of Laser ablation has increased safety. In recent years increasing numbers of drug resistant patients are opting for surgery. Many additional images, provocation tests and on the operating table brain mapping provide a more detailed location of the origin of the seizure and spare the functional areas of the brain.

Footnote:

Brain cells generate tiny electrical charges from various metabolic processes. These electrical activities can be recorded by placing electrodes on the head attached to a recording machine, unlike an EKG machine. Up to 64 electrodes and several hours of recording may be necessary to detect epileptic spikes. Each electrode records the activities of the cells directly underneath it and graphs are inscribed on a moving paper and all the leads record at the same time and each lead is identified by its position on the head.

In normal conditions, the brain cells are at different levels of activity and their activities are not synchronized. EEG of an epileptic discharge stands out as large waves and many adjoining leads record the same waveform synchronously.

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Regulation of the Body Temperature.

                                              Regulation of Body Temperature.

                                               PKGhatak, MD

Humans are warm-blooded and maintain a constant level of body temperature. The core or internal temperature is near constant and environmental factors do not change the core temperature. The shell or skin temperature is much lower and varies with the prevailing weather condition.

The core temperature is defined as the temperature recorded inside the body, recorded by inserting a temperature sensitive detector in the central vasculature. Oral and rectal temperatures also record the same. In normal conditions, the core temperature of humans is 37C (+/- 2C) or 98.7F. The skin temperature is lower and usually around 21C. and different in the exposed skin and covered skin areas.

Cellular functions are mostly derived from enzymes. The enzymes function at their maximum efficiency at core temperature. Certain immunocytes, however, can increase efficiency at a higher temperature. Maintaining a normal core temperature requires a steady state balance between heat generation and dissipation of heat from the body.

Sets of temperature sensors, a center for incoming information, sub-centers for coordination, and a center for outgoing instructions exist in the body just like a well designed environment control center.

Source of body heat:

Involuntary metabolic processes and physical work are the principal sources but warm food and drink also contribute to body heat.

Heat dissipation follows the Laws of Physics- evaporation, radiation, conduction and convection.

The distribution and equilibrium of heat in different compartments of the body are achieved by blood circulation and help maintain a constant core temperature.

Mechanism of heat generation.

Mitochondria are the metabolic factory of the body. As food is undergoing oxidative phosphorylation, the synthetic or secretory functions of cells are paired with it. This coupled action minimizes the loss of energy as heat.

The body has two distinct pathways to generate heat – (a) shivering and (b) uncoupled respiration and thermogenesis by brown fat.

(a) Shivering.

In exposure to cold, stress, fear, and in the face of danger, the body releases Adrenaline and Thyroxine. The effects of these hormones are many. The voluntary muscle mass responds to these inputs by muscle contractions and using up stored energy Glycogen as heat, CO2, and water.

(b) Uncoupled respiration.

The site of uncoupled respiration and heat generation takes place in the Brown fat. In fact, the brown color is due to the presence of large numbers of mitochondria in the fat cells. The oxidative phosphorylation is coupled with ATP (adenosine triple phosphate) generation. ATP is a high energy packet and the mitochondria use them for other functions requiring energy.

A protein, Thermogenine, regulates the rate of Proton (H+) transfer across the mitochondria and cell wall membranes. ATP generation depends on the availability of H+. Thermogenine keeps these two processes linked together. H+(proton) combines O-(- = electron) is the essence of cellular respiration. A H+ pump situated on the inner side of the mitochondrial membrane maintains the H+ gradient. In the situation when extra heat is required, the Thermogeneine uncouples the two processes and the H+ pump allows H+ to cross to the outside mitochondria membrane. This action stops ATP generation and increases heat production. Catecholamines, stress hormones, and sympathetic nerve impulses accelerate the rate of heat generation by recruiting additional mitochondria.

Minimizing heat loss.

Goosebumps or Piloerection. A tiny bunch of smooth muscle by contracting lifts the skin hair upright. Standing hairs in a close group, trap air in between providing a barrier to heat loss. The sympathetic nerve supplies the motor impulse for muscle contraction and adrenaline is the neurotransmitter of piloerection.

Dissipation of body heat.

In addition to the law of physics of the flow of heat from a higher temperature to a lower temperature, there are additional measures the body can utilize to lower body temperature.

Sweating. In summer we know how sweat cools the body. Sweat glands are adrenergic. And stress, anxiety, and fever also increase sweating.

Skin vasodilation.

In the non-hair region of the skin – the blood vessels of the palms, soles, and lips are supplied by only vasoconstrictor nerve fibers. There are special channels that connect skin arterioles to capillary loops in the top layer of the skin. At a higher temperature, the sympathetic tones of blood vessels are withdrawn, thereby increasing the skin blood flow. Cooling takes place by radiation.

Temperature sensors.

Skin sensors:

The entire skin is covered by sensors -touch, pain, pressure, position sensation, and cold and hot temperatures. The skin has separate cold and heat sensors. These are discussed elsewhere. The spinal nerves carry temperature sensation via the lateral spinothalamic tract of the spinal cord. The second order neurons of temperature are located in the lateral horn of the spinal cord, from there the information reaches the lateral parabrachial nucleus located in the dorsolateral pons. From there the sensation goes to the Median Preoptic Hypothalamic Nuclei. The second order neurons also carry the sensation by another tract to the ventromedial nucleus of the thalamus via the medial lemniscus.

A similar layout is seen in the sensory division of the 5^th cranial nerve carrying temperature sensation from the face. And the sensory division of the 9^th nerve from the structures of the mouth and throat. They carry the sensations to the ventromedial thalamic nuclei via the medial lemniscus.

Thalamus relays the sensations to (a). Preoptic Hypothalamus nuclei from there to the pituitary gland, (b). sensory cerebral cortex, (c). other midbrain nuclei.

Visceral censors:

The temperature sensors of the internal organs and central blood vessels are carried by the Vagus nerve. And then the sensations are relayed to the preoptic nuclei of the thalamus and from the Thalamus to the Hypothalamus – to the sensory cerebral cortex.

The diagram is taken from the Journal of Physiology, the authors are E.A. Tausey & C.D. Johnson. 

Regulating Center of Temperature.

The sensory input comes to the Median Preoptic nuclei of the Hypothalamus, and by another tract to the Ventromedial nuclei of the Thalamus.

The outgoing instructions are generated by the Medial Preoptic nuclei of the hypothalamus. These two sections of the hypothalamus are interconnected.

From the medial preoptic nuclei, the outgoing instruction is carried to the midbrain dorso-median nuclei of the thalamus. From there the outflow impulses are relayed to the Rostral Raphe Nucleus of the Globus Pallidum of the basal ganglia. Then the final instruction travels down the spinal cord to 1. Brown fat tissue. 2. Blood vessels of the skin. 3. The skeletal muscles.

The basic physiology of temperature regulation is known for nearly a century and additional information is regularly added. Biochemistry and biophysics of recent days added and refined the old information greatly and more is to come shortly. Infection, injury and state of shock change core temperature and contribute to the adverse outcome. The goal is to identify the molecular switches and then modify their actions to the benefit of the patients.

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Oxygen Radical

 

                                                        Oxygen Radical

                                                 PKGhatak, MD

The radicals are molecules containing an unpaired electron, and that makes them very reactive. Free radicals are highly reactive and unstable molecules containing unpaired electron., Radicals can damage the RNA and DNA and eventually can kill a cell.

 Oxygen.

 In the air, the oxygen is present in three different forms -

1. Oxygen molecule( O2,) 

2. Oxygen atom( O1)

 3. Ozone (O3).

Oxygen is a primary reactant, and the reaction gives out heat and it is called exothermic. 

Mitochondria are the main metabolic center of the cells; the more active the cell is, the greater the chance of generating radicals. The next order of cellular active sites is the endoplasmic reticulum, the cytosol, and the cell membrane.

Source of Oxygen Radical:

 Radicals are generated: Two sources - cellular and extracellular. The Non-cellular.  Air pollution, cigarette smoke, alcohol, Ozone, heavy metals, radiation, drugs, industrial solvents, pesticides, and herbicides are the main sources.

Oxygen Radicals and Non-Radical Oxidants.

Radical	Symbol	Oxidants	Symbol
Superoxide	O*-	Hydrogen peroxide	H2O2
Hydroxyl	*OH	Single Oxygen	1O2
Peroxyl	R00*	Ozone	O3
		Organic peroxide	ROOH
		Hypocaloric acid	HOCl
		Hypo bromic acid	HOBm

Nitrogenous Radicals and Oxidants.

Radical	Symbol	Oxidants	Symbol
Nitric acid	NO*	Peroxyl nitrogen	ONOO
Nitrogen dioxide	NO*2	Nitrosyl anions	NO
		Dinitro tetraoxide	N2O4
		Peroxyl nitrous acid	OHOOH
		Nitryl chloride	NO2Cl

The body's defense against radicals:

Mechanism of countermeasures against radical :

1.Superoxide dismutases (SOD) remove O2 by greatly accelerating its conversion to H2O2.

2. Catalases in peroxisomes convert H2O2 into water and O2 and help to dispose of H2O2 generated by the action of the oxidase enzymes that are located in these organelles.

3. Other important H2O2-removing enzymes in human cells are the glutathione peroxidases.

The human body employs Enzymes and Non-Enzymes to neutralize free radicals and oxidants.

A list of enzymes act as antiradicals and antioxidants - Superoxide dismutase, Catalase, Glutathione peroxidase,  and Glutathione reductase.

The Non-enzyme antioxidants are Vitamin E, Vitamin C, Carotenoids,  Trace metals Selenium and Zinc, Flavonoids, Omega 3 and Omega 6 fatty acids, L-arginine, Coenzyme Q10, and Melatonin.

Diseases caused by radicals in humans:

Age-related conditions- 

Loss of skin elasticity, wrinkles, cataracts, graying hair, and loss of hair.

Neurodegenerative diseases-

Parkinson's disease and Huntington's disease.

Autoimmune diseases-

Rheumatoid arthritis and various cancers.

Cardiovascular -

Coronary artery diseases.

edited May 2025

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A Look at the Diabetic Kidney.

                                              A look at the Diabetic Kidney

                                              PKGhatak, MD

Diabetes mellitus type II is a chronic illness and about 30 % of the patients show abnormal kidney function and the incidence is increasing; whereas diabetes mellitus type I is an acute illness and still about 20 % in 10 years, will develop renal involvement. This secondary renal disease is known as Diabetic Nephropathy. Diabetic nephropathy is a progressive disease and advances in stages. Drs. Kimmelstiel and Wilson described the pathological features and clinical aspects in great detail. They described the final stage of diabetic nephropathy as glomerular sclerosis, characterized by PSA positive modules replacing the glomeruli. The patients present with massive urinary protein leaks, generalized edema, hypertension and renal failure. The illness is known as Kimmelstiel Wilson Syndrome (KW syndrome) and KW nodules are pathognomic of the disease.

A glomerulus is the filtering unit of the kidney, consisting of a tuft of capillary, encased in a thin walled capsule- Bowman's capsule. The capsule continues as a tubule and ends in the pelvis of the kidney. Each glomerulus is supplied by an afferent arteriole – a tiny branch of the renal artery, and the blood exits from the glomerulus via the efferent arteriole. Each kidney contains about 1 million of these units.

Filter:

Renal filters are made up of three layers - Capillary walls are lined with fenestrated endothelial cells, lying on a basement membrane. The capillary tuft sits on a cushion of mesangial cells, accounting for 30 % of all the cells of a capsule. Mesangial cells originate separately from the kidney, then migrate to the developing kidney, some mesangial cells enter the Bowman's capsule, and others remain outside the capsule and are located in the space between the afferent and efferent arterioles. Mesangial cells have contractile protein, actin, and by selectively contracting and relaxing, can control blood flow and filtration pressure. In addition, these cells maintain the normal function of the basement membrane. They remove any tangled protein molecule in the basement membrane. The Mesangial cells can multiply when needed.

The capsular side of the endothelial cells is lined by Podocytes. The foot processes of the podocyte interdigitate with the foot process of the adjacent podocytes forming a fine network of filtering pores of about 50 nanometers in size overlying the fenestration of endothelial cells. Podocytes once damaged cannot repair or replace themselves.

Effect of high blood sugar on the filters.

High blood sugar induces metabolic stress in the renal cells. Glucose combines with amino acids forming glycosylate molecules and oxygen radicals. These molecules also add stress to the mesangial cells. Under stress, the mesangial cells multiply and secrete excess collagen, fibronectins and proteoglycans. These compounds change the filtering property of the basement membrane.

Effect on Macula densa.

Excess delivery of sugar to macula densa creates a relatively lower concentration of sodium chloride at this site. Macula densa cells signal renin secretion and activation of the renin-angiotensin-aldosterone pathway. This contributes to high BP.

Effect on Podocytes.

Higher afferent arterial pressure induces a shearing force damaging the delicate foot processes of podocytes and resulting in bigger filtration apertures. Serum albumin began to leak out of the blood in the filtrate. If this state is not reversed the protein loss will produce low blood albumin, low oncotic pressure and dependent edema.

In long standing diabetes, the above process gradually cuts off blood flow to individual small loops of glomerular capillaries. Initially, the closed capillaries appear as small isolated KW nodules. The small nodules coalesce together to form larger nodules.

Filtration:

In addition to the structural characteristic of the filter, the negative charges on the inner surface of the endothelial cells repel negatively charged protein molecules. Molecules of fat, cholesterol, hormones, and globulins are too large to pass through the filtering pores. The inorganic molecules dissolved in blood appear in the filtrate, however, 80 to 100 % are reabsorbed into the blood. Further modification of the filtrate continues along the tubule.

Cause of high BP.

Activation of renin-angiotensin-aldosterone is one main cause of hypertension. Constriction of the afferent arteriole and dilatation of efferent vessels increases filtration pressure and hyper-filtration takes place. This results in volume contraction and renin secretion, and intra-renal hypertension. Later, as the disease progress, produces systemic hypertension.

Cause of renal failure:

Disruption of renal arterial flow and changes in infiltration properties lead to the accumulation of creatinine and other waste products. In the very end, glomerulosclerosis ends in fibrosis of renal cortical tissue and the kidneys become atrophic.

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Kidney and Blood Pressure

                                                     Kidneys  and   Blood Pressure

                                                   PKGhatak, MD

A Blood Pressure (BP) of 120 mm Hg systolic and 80 mmHg diastolic, expressed as 120/80 mm Hg, is considered a normal BP in adults. When BP is over 140/80, it is called hypertension. In about 80% of cases, no definite cause of high BP will be detected. This is called Essential or Primary Hypertension. About 5 to 20 % of cases of high BP are due to kidney diseases.

Role of Kidney in maintaining a normal BP.

There are two systems that are operative. One is the Sympathetic nervous system and the other is the Angiotensin-Renin-Aldosterone system. These two systems are interconnected and act in a coordinated manner.

A. Sympathetic systems.

The BP sensors are located in the baroreceptors of the Carotid bodies and the Aortic bodies in the Aortic Arch. Any change in BP, high or low, initiates an impulse in the carotid stretch receptors in the carotid bodies and is carried by the Glossopharyngeal nerve and then relayed to the Hypothalamus. The pressure receptors of the aortic arch are sensitive only to falling BP. The Vagus nerve carries the sensation to the center and then relays it to the hypothalamus. From the hypothalamus, the outgoing impulse goes to the Celiac Ganglia. The postganglionic alpha fibers innervate all the systemic arteries and the beta fibers supply the heart.

The Hypothalamus also sends impulses to the adrenal glands and to the Juxtaglomerular cells of the kidneys.

Venous BP monitors: These are low-pressure monitors.

These monitors exist within large veins, pulmonary vessels, and within the walls of the right atrium and ventricle. Changes in volume influence the baroreceptors in the venous system and lead to the secretion of antidiuretic hormone and renin.

Effect of sympathetic alpha stimulation.

Arterial walls respond to alpha stimulation by increasing the tone of the muscular wall and the BP is raised. When the BP is high, the carotid body receptors produce a negative response in the hypothalamus, it prevents the further rise in BP. When BP falls, the aortic body sends positive impulses to the hypothalamus and BP is raised.

Effect of sympathetic Beta stimulation. Beta fibers mainly supply the heart. Stimulation of the beta fibers increases heart rate and force of ventricular contraction and elevation of BP.

Effect of sympathetic stimulation of the Adrenal glands. It increases the production and release of Aldosterone.

Effect of sympathetic stimulation of juxtaglomerular cells. It causes the secretion of Renin.

The action of the sympathetic system

Agent	Substrate	Response	Final effect
Alpha stimulation	Arterial wall	Vasoconstriction	BP elevation
Beta stimulation	Heart muscles	Rate and force of contraction	BP elevation
	Adrenal Glands	Aldosterone release	Increased Na+ absorption in exchange for K+
	Juxtaglomerular cells	Renin release	Angiotensin I formation
	Posterior Pituitary	ADH release	Blood volume increase

B. Angiotensin-Renin-Aldosterone system.

BP sensors.

The outer wall of the afferent arteriole of the kidney contains BP sensors. When blood flow/ pressure is low, these cells secrete Paracrine molecules (paracrine are chemicals, have actions like hormones but these chemicals are locally released and locally active). These molecules stimulate Juxtaglomerular cells to produce and release Renin.

Electrolyte sensors.

The Macula Densa cells of the distal convoluted tubules are specialized endothelial cells. They continuously monitor Sodium and Chloride concentrations of the glomerular fluid. Any fall in sodium chloride concentration triggers the paracrine release. Paracrine increases the rate of excretion of Potassium+ ion and H+ion production and release in exchange for Sodium+ ion from the filtrate.

Angiotensinogen is an alpha2 globulin produced by the liver and renal endothelial cells and circulates in the blood and is a non-active molecule. Renin converts angiotensinogen to angiotensin I. Angiotensin I is carried by the renal veins to the inferior vena cava to the right side of the heart and then to the lungs. In the pulmonary capillaries, the endothelial cells secrete Angiotensin Converting Enzyme (ACE). ACE converts angiotensin I to angiotensin II. In the blood, angiotensin lasts about 30 seconds and in the tissues for about 15 minutes, then it is degraded by ACE to Angiotensin III and Angiotensin IV. Both angiotensin III & IV have variable effects but are in the same line as angiotensin II.

Angiotensinogen is also produced by the fat cells, testicles, ovaries, brain, heart and blood vessels. In these secondary locations, its functions are limited at the local tissue levels.

Effect of Angiotensin II:

Angiotensin II has a multitude of functions. 1. It increases the tone of all systemic arteries and veins. 2. Constricts afferent and efferent arterioles of the glomerulus. and thereby increases filtration pressure and the GFR (glomerular filtration rate) is increased. 3. Angiotensin II increases the rate of Na+ ion reabsorption in the proximal tubules. 4. It accelerates Na+/K+ H+ exchange in distal convoluted tubules. 5. Angiotensin II causes the secretion of aldosterone by the adrenal cortex. 6. It releases an Antidiuretic hormone from the Posterior pituitary gland.

Na+/K+H+ ion exchange and water reabsorption produce an increase in total body Sodium and a decrease in potassium. The total body intravascular volume expansion takes place. The serum becomes alkalotic due to execs HCO3- ions. This condition is called Hypokalemia alkalosis.

Effect of Anti Diuretic Hormone (ADH).

ADH increases water absorption in the collecting tubules from the filtrate, thereby increasing blood volume. However, expansion of blood volume takes place only when both kidneys are ischemic. If only one kidney remains normal, then increased glomerular filtrate and loss of Sodium and water by the normal kidney in the urine keep the blood volume normal, but BP remains high.

Role of Kidneys in producing High BP:

Any condition producing a decrease in blood flow in the Kidneys (ischemic) produces high BP.

Renal causes of hypertension are discussed under

1. Renal- vascular

2. Renal parenchymal causes.

Of all the causes of Hypertension, renovascular hypertension has the most potential to be cured by corrective surgery and usually, the patients are not required to take BP medications. It is essential to find the cause of high BP before much damage takes place.

 1. Common causes of Renovascular hypertension.

In children:

Common causes are coarctation of the aorta, Moyamoya disease. Kawasaki disease, Takayasu arteritis, renal artery trauma, congenital renal artery hypoplasia or renal artery stenosis and renal graft stenosis following renal transplantation.

Moyamoya disease is more prevalent in Japan and is probably inherited by autosomal dominant inheritance. Cerebral arteries are deformed and various degrees of neurological symptoms develop at a very early age. Kawasaki disease is a multisystem inflammatory disease that usually follows a viral infection and produces signs and symptoms involving the skin, mucous membrane and lymph nodes and internal organs. It is more prevalent in China. Takayasu arteritis is an inflammatory disease of the aorta and its main branches,  producing narrowing of blood vessels and aneurysms,  producing severe ischemia to the involved areas like arms, neck, brain and kidneys. There is no known cause and treatment is not effective. It is often seen in Japan, Mexico, and India.

In adults:

The common pathology is renal artery stenosis due to atheromatous plaques.

The narrowing may be in one or both renal arteries. The plaques may be only segmental or in multiple areas, commonly involve the proximal third of the artery. The plaques develop the same way as in the coronary arteries. The risk factors are diabetes, high BP, high cholesterol, obesity, cigarette smoking, a sedentary lifestyle, and runs in a family.

Other causes of renal artery diseases are Congenital stenosis, Renal artery thrombosis, emboli, aortic dissection, A-V malformation, and aneurysm of the abdominal aorta.

In young females:

Fibromuscular dysplasia. This condition is largely confined to females of childbearing age. The condition may run in families. The medium size arteries are involved. Common sites are renal, intracranial, face and abdominal. The distal 2/3rd of the renal artery shows dysplasia. The changes may be confined in one or all three layers of the arterial wall. Bead-sized aneurysms are seen in cerebral branches of carotid arteries.

Risk factors are female hormones, the higher incidence of methysergide use in migraine, cigarette smoking, alpha 1 antitrypsin deficiency, cystic medial necrosis, neurofibromatosis, coarctation of the aorta and Ehler-Danlos syndrome.

The patients with fibromuscular hypoplasia are mostly symptoms free. A cerebrovascular episode like TIA, (transient ischemic attack) or subarachnoid hemorrhagic may lead to a diagnosis of fibromuscular dysplasia of the renal artery.

2. Renal parenchymal diseases cause hypertension.

Almost all inflammatory diseases of the kidneys raise BP.  A few common conditions are: -

Polycystic disease of the kidney. Glomerulonephritis.

Polycystic disease of the kidney is the most common hereditary kidney disease in adults causing hypertension and other complications. It is inherited as a dominant mode, and the expression of the defective gene penetration is variable. In children, the disease is much less aggressive and provides a better prognosis.

Glomerulonephritis is generally due to post-streptococcal pharyngitis, also seen in secondary to Bacterial endocarditis, Hepatitis B, hepatitis C, HIV infection and now COVID-19. Other less common causes are autoimmune glomerulonephritis. Lupus, Goodpasture syndrome, IgA nephropathy, Diabetic microvascular disease,

Investigation and Diagnosis:

The renal parenchymal disease is evident by the presence of protein, RBC, red cell casts and granular casts in the urine. If active infection is present, an increased number of WBCs and WBC casts are detected in urine. Further tests, including IgG, IgA and other serological tests are generally required for the determination of the etiology in individual cases. In most cases, needle biopsy of the kidney and special immunological staining is required to properly direct medical therapy and evaluate prognosis.

Renovascular disease is detected by an Ultrasonography of the abdomen. It is a noninvasive test and can easily detect abdominal aortic aneurysm, dissection of the aorta, atheromatous changes and fibromuscular dysplasia. The new generation Doppler ultrasound study gives flow and degree of stenosis. In case the presence of gas in the bowel interferes with the ultrasound study, MRI is an excellent alternative. The functional status of kidneys is determined by serum creatinine, urinary creatinine and GFR, electrolytes. Radio-opaque dye administration is held off till a definite surgery is planned. In a situation that is likely to be associated with vascular abnormalities of the brain and other vital organs, then a whole body angiogram may be completed before surgery.

Treatment:

Renal artery stenosis is treated by angioplasty and stent placement. This is the preferred treatment for fibromuscular dysplasia and a stent often is not needed.

Resection, repair and Dacron graft are used based on the nature of the pathology. In unilateral and atrophic kidney nephrectomy is indicated. Post-surgery prognosis is very good for children and young individuals.

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