Dr.Tamim

Pernicious Anemia

Pernicious anemia is a relatively rare autoimmune disorder that causes diminishment in dietary vitamin B12 absorption, resulting in B12 deficiency and subsequent megaloblastic anemia. It affects people of all ages worldwide, particularly those over 60. Despite the advances in understanding, making the diagnosis can be challenging for clinicians due to its complexity, broad spectrum of clinical presentation, and limitations of the currently available diagnostic tests. Once diagnosed, prompt treatment with B12 supplementation commonly reverses the patient's anemia; however, they will require lifelong supplementation and monitoring. This activity reviews the etiology, evaluation, and treatment of pernicious anemia and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

●Etiology
Pernicious anemia is a complex disease, with a clear autoimmune basis. The anemia is megaloblastic and is caused by vitamin B12 deficiency secondary to intrinsic factor (IF) deficiency. IF is a glycoprotein produced and secreted by parietal cells that binds B12 and facilitates its transport to the terminal ileum for absorption. Anti-IF antibodies inhibit B12 from binding to IF, preventing B12/IF complex formation or binding to the B12/IF complex, preventing intestinal absorption.

Pernicious anemia is found in up to 25% of patients with autoimmune gastritis (AIG), which affects the corpus and fundus, spares the antrum, and is characterized by antiparietal cell antibodies destroying parietal cells located only in the oxyntic mucosa, which produce IF and hydrochloric acid. In turn, achlorhydria causes a decrease in the release of cobalamin bound to dietary protein, and fewer parietal cells are available to produce the IF needed for dietary B12 absorption. The term pernicious anemia has been used at times as a synonym for AIG; however, it is considered a late-stage manifestation as a part of the AIG clinical spectrum.

Patients with pernicious anemia also have a higher incidence of co-occurring autoimmune disorders, including diabetes mellitus type 1, autoimmune thyroid disease, and vitiligo.Furthermore, 5 genome-wide significant signals for pernicious anemia have been identified, providing evidence for genetic risk factors.

Whether or not Helicobacter pylori plays a causative role in pernicious anemia is unclear.

●Epidemiology
Pernicious anemia is a relatively rare condition, with a prevalence of less than 1% in populations of European ancestry. Worldwide, pernicious anemia is a common cause of megaloblastic anemia; it affects people of all ages, particularly those over 60-70 (~2% prevalence); it affects both sexes with a varying geographical female-to-male ratio; and the prevalence is lower in those of Asian descent compared to other studied populations.

●Pathophysiology
The primary pathophysiological mechanism in pernicious anemia is diminished dietary B12 absorption due to IF deficiency. Vitamin B12 is found in meat, eggs, and dairy products and is essential for erythropoiesis and nerve myelination; therefore, its deficiency can lead to megaloblastic anemia due to disrupted DNA synthesis and demyelinated nerves. B12 deficiency causes megaloblastic changes in all formed blood elements, but erythrocytes show the most significant changes, with the degree of anemia corresponding to the severity of red blood cell morphologic changes.

Dietary B12 is released from food carrier proteins via proteolysis in the acidic gastric environment and binds to haptocorrin, protecting B12 from degradation.B12 is released from haptocorrin in the small intestine by pancreatic proteases and binds to IF produced by gastric parietal cells. The IF-B12 complex binds to cubam receptors in the terminal ileum, is endocytosed, binds to transcobalamin, then is released in the bloodstream and delivered to transcobalamin cell receptors. After cellular uptake and intracellular release, B12 is converted to adenosylcobalamin and methylcobalamin, where they serve as cofactors for the two B12-dependent enzymatic reactions.

Vitamin B12 deficiency prevents the proper functioning of these coenzymes, leading to an accumulation of their substrate in plasma. Specifically, adenosylcobalamin deficiency results in an accumulation of methylmalonic acid (MMA), and methylcobalamin deficiency in an accumulation of homocysteine. Additionally, the formation of S-adenosylmethionine (SAM) and methionine diminish.

SAM is the methyl donor to key substrates, such as nucleic acids, proteins, phospholipids, and neurotransmitters. As a donor in DNA methylation, it plays an important role in epigenetic adaptability to developmental and environmental factors.
Homocysteine excess can cause cellular stress, apoptosis, and homocysteinylation-induced structural and functional alterations in proteins. Moreover, elevated plasma total homocysteine is associated with white matter damage, neurofibrillary tangles, brain atrophy, cognitive decline, and dementia. The effects of accumulated MMA are unclear.

●History and Physical
Pernicious anemia develops slowly, with a progression time to apparent clinical B12 deficiency of 2 to 5 years.
Symptoms may not manifest until the anemia is relatively profound because compensatory cardiopulmonary mechanisms facilitate increases in oxygen delivery. Due to its insidious nature and the wide array of potential presenting symptoms, a high index of clinical suspicion is often necessary for the judicious use of appropriate testing to make a prompt diagnosis. Patients may present with constitutional, neurological, psychiatric, otolaryngologic, cardiopulmonary, and/or gastrointestinal symptoms, which are often present in other conditions, resulting in a missed or delayed diagnosis.

Constitutional: fatigue, lethargy, anorexia, weight loss
Neurological: headache, confusion, difficulty concentrating, memory loss, cognitive decline, paraesthesias, numbness, imbalance
Psychiatric: emotional lability, depression, personality changes, psychosis
Otolaryngologic: hypogeusia/ageusia, glossitis
Cardiopulmonary: palpitations, dyspnea
Gastrointestinal: dyspepsia, diarrhea, decreased appetite
The physical examination may be notable for pallor, dry skin, jaundice, glossitis (tender, smooth, red tongue), and tachycardia. In patients of European ancestry, “the melding of severe pallor with jaundice caused by hemolysis produces a peculiar lemon-yellow skin color."

Peripheral neuropathy is an early neurological manifestation, which may be followed by subacute combined degeneration (SCD) of the spinal cord in later stages. It is typically symmetric and affects the legs more than the arms. Examination shows a decrease in sensitivity to light touch, pinprick, and vibration. Patients with severe loss of position sense may demonstrate a positive Romberg test. Deep tendon ankle reflexes are commonly hypoactive or absent, while more proximal reflexes may still be intact. Importantly, neurologic findings may be present in the absence of anemia. Examination of a patient with SCD will likely demonstrate limb weakness and ataxia, and they may report visual disturbances. The prompt recognition of SCD is important because early diagnosis and treatment improve the chances of recovery.

A neuropsychiatric evaluation may be required.Additionally, the clinician should inquire whether the patient, a parent, or a sibling has diabetes mellitus type 1, vitiligo, or hypothyroidism because a positive personal or family history of an autoimmune condition increases the pretest probability of pernicious anemia.

●Evaluation
Making a definitive diagnosis of pernicious anemia can be “problematic” due to the Schilling test becoming obsolete and the absence of a currently approved B12 absorption test.Furthermore, there are multiple diagnostic algorithms and varying diagnostic criteria. Evaluation will likely include a combination of the following:

Initial serology: complete blood count (CBC), cobalamin level, folate level, iron panel (serum iron, total iron-binding capacity, ferritin), reticulocyte count
Peripheral blood smear
Follow-up serology: anti-IF antibodies, antiparietal cell antibodies
Additional serology: MMA, fasting homocysteine, holotranscobalamin (HTC)
Bone marrow biopsy
Endoscopy with biopsies
A CBC may be significant for anemia, macrocytosis (mean corpuscular volume ≥100 fl), and pancytopenia (due to ineffective erythropoiesis and myelopoiesis). However, about one-third of patients with B12 deficiency may not have macrocytosis.Normocytic anemia can be seen if there is concomitant iron deficiency anemia, a complication of achlorhydria, or another condition causing microcytosis that can mask the macrocytosis. Iron deficiency may precede a pernicious anemia diagnosis or be concomitant with it. Moreover, pernicious anemia can present with nonanemic macrocytosis months before the diagnosis and neurologic signs and symptoms can occur in the absence of anemia or macrocytosis in 25 to 30% of patients eventually diagnosed with pernicious anemia. A reticulocyte count may show a reduction in the absolute number of reticulocytes.

A peripheral blood smear may show macro-ovalocytes, hypersegmented neutrophils, and anisopoikilocytosis. Although hypersegmented neutrophils are often considered a hallmark of megaloblastic anemia, they are not specific, as they can be seen in other types of anemia, like iron deficiency anemia. Hypersegmented neutrophils typically precede macrocytosis and anemia; however, in advanced disease, they may be rare or absent.

An isolated serum cobalamin level has poor sensitivity and specificity for reliably detecting B12 deficiency.B12 deficiency is defined by a serum cobalamin level of

مرد 3️⃣3️⃣ ساله 👨 با تاریخچه مصرف #سگریت 🚬 و اعتیاد به ، با درد شدید سینه به شفاخانه مراجعه نمود و گراف قلب حمله بزرگ قلبی را نشان داد. قبل از انتقال مریض به کیت لیب (اطاق عمل انجیوگرافی) در اطاق عاجل اریست (توقف فعالیت) قلبی تنفسی نمود❌️. به تعقیب احیایی مجدد و وصل شدن مریض به دستگاه تنفس مصنوعی یا وینتیلاتور، مریض تحت معاینه انجیوگرافی قرار گرفت که بندش کامل رگ اصلی سمت چپ قلب را نشان داد و با گذاشتن استنت رگ مریض موفقانه باز گردید ✅️

👈 مصرف سگریت 🚬 و تنباکو باب خطر حمله قلبی را 2️⃣ الی 4️⃣ چند افزایش می دهد.

مشهد، شفاخانه قایم

Endocarditis

Infective endocarditis is an infection of the inner layer of the heart, usually involving the heart valves.

■Causes of Infective Endocarditis

Infective endocarditis occurs when a bacterial or fungal pathogen enters the blood and attaches to the inner lining of the heart (the endocardium), usually a heart valve. The organisms that cause the infection can enter blood through the gums or intestines; by health care–related procedures such as intravenous catheter placement, surgery, or hemodialysis; or through the skin because of intravenous drug abuse. People who have artificial heart valves or congenital heart abnormalities or who have had endocarditis in the past have a high risk of developing endocarditis.

■Symptoms

Infective endocarditis causes fever in most but not all patients. Other symptoms may be fatigue (feeling tired), shortness of breath, swelling of hands or feet, painful lesions on the fingers or toes, and even having a stroke. A doctor might check for a new or worsening heart murmur, heart failure, an enlarged spleen, stroke, or abnormal spots on the hands or feet.

■Diagnosis

A blood sample may be taken to check for pathogens. An echocardiogram (ultrasound of the heart) may be used to detect infection of the heart valves. Sometimes it may be necessary to pass a scope into the esophagus through the mouth to view the heart using an ultrasound device (transesophageal echocardiography).

■Treatment

Infective endocarditis is treated with antibiotics that targeted the bacteria or fungus causing the infection. Patients usually receive a long course of these antibiotics, usually 4 to 6 weeks. Some patients require surgical repair or replacement of the infected heart valve, particularly if mechanical complications in the infected valve cause heart problems.

Poor oral hygiene or gum disease increases the risk of bacteria entering the blood and development of endocarditis. Patients who have a high risk of developing endocarditis should make sure to brush their teeth regularly and get regular dental care. At-risk patients also may need to receive antibiotics before they have any kind of procedure that might cause bacteria to get into the bloodstream.

What is hydrocephalus?

Hydrocephalus, also called water in the brain, is a condition where there is an abnormal build up of CSF (cerebrospinal fluid) in the cavities (ventricles) of the brain. The build-up is often caused by an obstruction that prevents proper fluid drainage.
In hydrocephalus, the build-up of CSF can raise pressure inside the skull, which squashes surrounding brain tissue.

In some cases, this can cause the head to steadily grow in size, convulsions, and brain damage. Hydrocephalus can be fatal if left untreated.

Other symptoms include headaches, vomiting, blurred vision, cognitive problems, and walking difficulties.

The outlook for a patient with hydrocephalus depends mainly on how quickly the condition is diagnosed and treated, and whether there are any underlying disorders.

The term “water in the brain” is incorrect, because the brain is surrounded by CSF (cerebrospinal fluid), not water. CSF has three vital functions, it:

1-protects the nervous system
2-removes waste
3-nourishes the brain
The brain produces about 1 pint of CSF each day, and old CSF is absorbed into blood vessels. If the process of producing and removing CSF is disturbed, CSF can accumulate, causing hydrocephalus.

Types
There are a number of types of hydrocephalus:

●Congenital hydrocephalus
Approximately 1 in every 500 American babies are born with hydrocephalus. It may be caused by an infection in the mother during pregnancy, such as rubella or mumps, or a birth defect, such as spina bifida. It is one of the most common developmental disabilities, more common than Down syndrome or deafness.

●Acquired hydrocephalus
This develops after birth, usually after a stroke, brain tumor, meningitis, or as a result of a serious head injury.

●Communicating hydrocephalus
This type of hydrocephalus occurs when the CSF becomes blocked after leaving the ventricles. It is called “communicating” because CSF can still flow between the brain’s ventricles.

●Non-communicating hydrocephalus
Also called obstructive hydrocephalus, non-communicating hydrocephalus occurs when the thin connections between the ventricles become blocked.

●Normal pressure hydrocephalus
This only affects people aged 50 or older. It may develop after stroke, injury, infection, surgery, or hemorrhage. However, in many cases, doctors do not know why it occurred. An estimated 375,000 older adults in America have normal pressure hydrocephalus.

●Hydrocephalus ex-vacuo
This type occurs after stroke, traumatic brain injury, or degenerative diseases. As brain tissue shrinks, the ventricles of the brain become larger.

■Symptoms
Symptoms of congenital hydrocephalus (present at birth):
breathing difficulties
arm and leg muscles may be stiff and prone to contractions
some developmental stages may be delayed, such as sitting up or crawling
the fontanel, the soft spot on the top of the head, is tense and bulges outward
irritability, drowsiness, or both
unwillingness to bend or move the neck or head.
poor feeding
the head seems larger than it should be
the scalp is thin and shiny and there may be visible veins on the scalp
pupils of the eyes may be close to the bottom of the eyelid, sometimes known as “the setting sun”
there may be a high-pitched cry
possible seizures
possible vomiting
Symptoms of acquired hydrocephalus, which develops after birth, are:
rarely, bowel incontinence
confusion, disorientation, or both
drowsiness and lethargy
headaches
irritability, which may get worse
lack of appetite
nausea
personality changes
problems with eyesight, such as blurred or double vision
seizures or fits
urinary incontinence
vomiting
walking difficulties, especially in adults
Symptoms of normal pressure
hydrocephalus. Signs and symptoms may take many months or years to develop.

Changes in gait: The person may feel as if they are frozen on the spot when taking their first step to start walking. They may appear to shuffle rather than walk.
Normal thinking process slows down: The person may respond to questions more slowly than normal, there may be delayed reactions to situations. The individual’s ability to process information slows down.
Urinary incontinence: This usually comes after changes in gait.

■Risk factors
The following factors increase the risk of hydrocephalus:

Premature birth: Infants born preterm have a higher risk of intraventricular hemorrhage, or bleeding within the ventricles of the brain, which may result in hydrocephalus.
Problems during pregnancy: An infection in the uterus during pregnancy increases the risk of hydrocephalus in the developing fetus.
Problems with fetal development:
Examples include incomplete closure of the spinal column.

Other conditions that increase the risk include:
lesion and tumors of the spinal cord or brain
infections of the nervous system
bleeding in the brain
severe head injury

■Causes
Hydrocephalus occurs when too much fluid builds up in the brain; specifically, excess CSF (cerebrospinal fluid) accumulates in the cavities (ventricles) of the brain.

There are more than 100 possible causes of hydrocephalus, but the underlying reasons are:
Too much CSF is produced.
One of the ventricles in the brain is blocked or narrowed, stopping or restricting the flow of CSF, so that it cannot leave the brain.
CSF cannot filter into the bloodstream.
Causes of congenital hydrocephalus (present at birth)
The baby is born with a blockage in the cerebral aqueduct, a long passage in the midbrain that connects two large ventricles. This is the most common cause.
The choroid plexus produces too much CSF.

Health conditions in the developing baby can cause problems in how the brain develops. For instance, hydrocephalus is common in children with severe spina bifida (a birth defect of the spinal cord).

Infections during pregnancy – these can affect the development of the baby’s brain. Examples include:

CMV (cytomegalovirus)
German measles (rubella)
mumps
syphilis
toxoplasmosis

■Causes of acquired hydrocephalus
This condition develops after birth and is usually caused by an injury or illness that results in blockage between the ventricles. The following may be causes:

Brain hemorrhage – bleeding inside the brain.
Brain lesions – areas of injury or disease within the brain. There are many possible causes, including injury, infection, exposure to certain chemicals, or problems with the immune system.
Brain tumors – benign (noncancerous) or malignant (cancerous) growths in the brain.
Meningitis – inflammation of the membranes of the brain or spinal cord.
Stroke – a condition where a blood clot or ruptured artery or blood vessel interrupts blood flow to an area of the brain.

■ Causes of normal pressure hydrocephalus
This condition affects people aged at least 50 – in most cases, doctors don’t know what caused it. Sometimes, it may develop after a stroke, infection, or injury to the brain.

There are two theories:

CSF is not reabsorbed into the bloodstream properly. Because of this, the brain starts to produce less new CSF, resulting in a gradual rise in pressure over a long period. The gradual rise in pressure may cause progressive brain damage.
An underlying condition, such as heart disease, high blood cholesterol level, or diabetes affects normal blood flow, which may lead to a softening of brain tissue. The softened brain tissue results in increasing pressure.

■Diagnosis
Babies and young children (congenital hydrocephalus):

A routine prenatal ultrasound scan may detect hydrocephalus during pregnancy in the developing fetus.

After birth, the head of the baby is measured regularly. Any abnormalities in head size will probably lead to further diagnostic tests.

If an ultrasound scan shows any abnormality, further tests will be ordered, such as an MRI (magnetic resonance imaging) scan or a CT (computerized tomography) scan, which give more detailed images of the brain.

■Acquired hydrocephalus (occurs after birth) – if the child or adult develops the signs and symptoms of hydrocephalus the doctor will:

Examine the patient’s medical history.
Carry out a physical and neurological examination.
Order an imaging scan, such as a CT or MRI scan.

■Normal pressure hydrocephalus – diagnosing this type of hydrocephalus is more tricky because symptoms are more subtle and do not appear suddenly.

■Treatments
In this section, we will discuss treatments for congenital and acquired hydrocephalus and treatments for normal pressure hydrocephalus individually.

Treatments for congenital and acquired hydrocephalus.
Both types of hydrocephalus require urgent treatment to reduce the pressure on the brain; otherwise, there is a serious risk of damage to the brainstem, which regulates functions such as our breathing and heartbeat.

A shunt is the surgical insertion of a drainage system. A catheter (a thin tube with a valve) is placed in the brain to drain away excess fluid from the brain into another part of the body, such as the abdomen "VP shunt," the chest cavity, or a chamber of the heart. Usually, this is all that is needed, and no further treatment is required.

Patients with hydrocephalus will usually need to have a shunt system in place for the rest of their lives. If the shunt is placed in a child, additional surgeries may be needed to insert longer tubing as they grow.

Ventriculostomy – the surgeon makes a hole in the bottom of a ventricle so that the excess fluid flows towards the base of the brain. Normal absorption occurs at the base of the brain. This procedure is sometimes performed when the flow of fluids between ventricles is obstructed.

■Treatment for normal pressure hydrocephalus
Shunts may also be used for normal pressure hydrocephalus. However, shunts may not be suitable for some patients. Other procedures may be carried out to check suitability:

Lumbar puncture – some of the cerebrospinal fluid is removed from the base of the spine. If this improves the patient’s gait or mental abilities, fitting a shunt will probably help.

Lumbar infusion test – a needle is inserted through the skin of the lower back into the spine. Measurements are taken of CSF pressure as fluid is injected into the spine. Patients usually benefit from having a shunt fitted if their CSF pressure is over a certain limit.

■Complications
Hydrocephalus severity depends on several factors, including when it develops and how it progresses. If the condition is advanced when the baby is born, it is more likely there will be brain damage and physical disabilities. If cases are not so severe and treatment is proper and prompt, the outlook is much better.

Babies with congenital hydrocephalus may experience some permanent brain damage, which can result in long-term complications. Examples include:

●A limited attention span
●Autism
●Learning difficulties
●Physical coordination problems
●Problems with memory
●Speech problems
●Vision problems