Rickets - Bony manifestation of altered Vit. D, Calcium, and phosphorus metabolism
- Rickets – child;
- Osteomalacia – adult form
there is an inability to mineralize chondroid and osteoid
- lack of available calcium or phosphorus (or both) for mineralization of newly formed osteoid
- osseous changes in both adults and children
--- Definition - a defect in mineralization of osteoid matrix caused by inadequate calcium and phosphate deposition prior to closure of physis.
- Clinical features arise from un-mineralized matrix at the growth plate.
- less mineralized bone per unit volume of bone
- classic changes of rickets will typically occur in children younger than 6-7 years of age
-- Pathophysiology of Rickets
- Vitamin D => increase the absorption of calcium from intestine
PTH => mobilizes calcium from bone and increases urinary excretion of phosphate
Calcitonin => inhibits bone resorption
CLINICAL FEATURES
Head:
Craniotabes — softening of cranial bones. also seen in osteogenesis imperfect, hydrocephalus and syphilis
Frontal bossing
Delayed dentition and tooth caries
Delayed closure of fontanel
Craniosynostosis.
Chest
Rachitic rosary — widening of osteochondral junction
Harrison’s groove — occurs due to pulling of softened ribs in inspiration by diaphragm. Softened ribs also predispose to atelectasis and pneumonia because of decreased air entry
Pectus carinatum (pigeon breast)
Spine
Scoliosis (uncommon)
Kyphosis (rachitic cat back)
Accentuation of lumbar lordosis
Limbs and Joints
Bone pain and tenderness
Coxa vara
Genu valgum or varum
Windswept deformity
Bowing of tibia, femur, radius and ulna
Widening of wrist, elbow, knee and ankle because of enlargement of ends of long bones
Rachitic saber shins
Sausage like enlargement of ends of phalanges and metacarpals, with regular constrictions corresponding of the joints string of pearls deformity
Double malleoli sign
General
Failure to thrive
Protuberant abdomen
Apathy, listlessness and irritability
Proximal muscle weakness
Ligament laxity
Symptoms of hypocalcemia—tetany, seizures and stridor due to laryngeal spasm
Bilateral lamellar cataract (Vitamin D deficiency in early infancy).
RADIOLOGICAL SIGNS
Generalized osteopenia
Bowing deformities of the long bones, femur and tibia
Widening of the growth plate
Cupping or flaring of the metaphysis
Radiographic findings in vitamin D resistant rickets
similar to those in infantile rickets
Bowing deformities and shortening of the long bones => more pronounced in early rickets
More common in distal ends of radius and ulna (more so in ulna)
Changes in the shaft appear a few weeks later than metaphysis.
The epiphysis is cloudy and indistinct and periosteum is thick.
The shaft shows diffuse rarefaction, thin cortices with coarse texture of spongiosa.
Umbau zones (Looser’s zones) => sharply defined radiolucent transverse zones
-- Findings of healing rickets:
Earliest finding => reappearance of the provisional zone of calcification, which gradually thickens
Rickets - Bony manifestation of altered Vit. D, Calcium, and phosphorus metabolism
- Rickets – child;
- Osteomalacia – adult form
there is an inability to mineralize chondroid and osteoid
- lack of available calcium or phosphorus (or both) for mineralization of newly formed osteoid
- osseous changes in both adults and children
--- Definition - a defect in mineralization of osteoid matrix caused by inadequate calcium and phosphate deposition prior to closure of physis.
- Clinical features arise from un-mineralized matrix at the growth plate.
- less mineralized bone per unit volume of bone
- classic changes of rickets will typically occur in children younger than 6-7 years of age
-- Pathophysiology of Rickets
- Vitamin D => increase the absorption of calcium from intestine
PTH => mobilizes calcium from bone and increases urinary excretion of phosphate
Calcitonin => inhibits bone resorption
CLINICAL FEATURES
Head:
Craniotabes — softening of cranial bones. also seen in osteogenesis imperfect, hydrocephalus and syphilis
Frontal bossing
Delayed dentition and tooth caries
Delayed closure of fontanel
Craniosynostosis.
Chest
Rachitic rosary — widening of osteochondral junction
Harrison’s groove — occurs due to pulling of softened ribs in inspiration by diaphragm. Softened ribs also predispose to atelectasis and pneumonia because of decreased air entry
Pectus carinatum (pigeon breast)
Spine
Scoliosis (uncommon)
Kyphosis (rachitic cat back)
Accentuation of lumbar lordosis
Limbs and Joints
Bone pain and tenderness
Coxa vara
Genu valgum or varum
Windswept deformity
Bowing of tibia, femur, radius and ulna
Widening of wrist, elbow, knee and ankle because of enlargement of ends of long bones
Rachitic saber shins
Sausage like enlargement of ends of phalanges and metacarpals, with regular constrictions corresponding of the joints string of pearls deformity
Double malleoli sign
General
Failure to thrive
Protuberant abdomen
Apathy, listlessness and irritability
Proximal muscle weakness
Ligament laxity
Symptoms of hypocalcemia—tetany, seizures and stridor due to laryngeal spasm
Bilateral lamellar cataract (Vitamin D deficiency in early infancy).
RADIOLOGICAL SIGNS
Generalized osteopenia
Bowing deformities of the long bones, femur and tibia
Widening of the growth plate
Cupping or flaring of the metaphysis
Radiographic findings in vitamin D resistant rickets
similar to those in infantile rickets
Bowing deformities and shortening of the long bones => more pronounced in early rickets
More common in distal ends of radius and ulna (more so in ulna)
Changes in the shaft appear a few weeks later than metaphysis.
The epiphysis is cloudy and indistinct and periosteum is thick.
The shaft shows diffuse rarefaction, thin cortices with coarse texture of spongiosa.
Umbau zones (Looser’s zones) => sharply defined radiolucent transverse zones
-- Findings of healing rickets:
Earliest finding => reappearance of the provisional zone of calcification, which gradually thickens
INTRODUCTION — Normal bone growth and mineralization require adequate calcium and phosphate, the two major constituents of the crystalline component of bone. Deficient mineralization can result in rickets and/or osteomalacia. Rickets refers to deficient mineralization at the growth plate, as well as architectural disruption of this structure. Osteomalacia refers to impaired mineralization of the bone matrix. Rickets and osteomalacia usually occur together as long as the growth plates are open; only osteomalacia occurs after the growth plates have fused.
rickets is a nutritional deficiency disease that involves mainly calcium, vitamin d, or phosphate resulting in decreased bone stability and strength, Delayed closure of the fontanelles,Parietal and frontal bossing. Craniotabes (soft skull bones).
Enlargement of the costochondral junction visible as beading along the anterolateral aspects of the chest (the "rachitic rosary") . Formation of Harrison sulcus (or groove),Widening of the wrist and bowing of the distal radius and ulna, Progressive lateral bowing of the femur and tibia and causes defects in teeth.
there is two types of rickets: phosphopenic and calcipenic.
pathogenesis: Growth plate thickness is determined by two opposing processes: o chondrocyte proliferation and hypertrophy on the one hand. o vascular invasion of the growth plate followed by conversion into primary bone spongiosa on the other. • Vascular invasion requires mineralization of the growth plate cartilage and is delayed or prevented by deficiency of calcium or phosphorus growth plate cartilage accumulates and the growth plate thickens. • In addition, the chondrocytes of the growth plate become disorganized, losing their columnar orientation with characteristic expansion of the hypertrophic zone. • In the bone tissue below the growth plate (metaphysis), the mineralization defect leads to the accumulation of osteoid.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
INTRODUCTION — Normal bone growth and mineralization require adequate calcium and phosphate, the two major constituents of the crystalline component of bone. Deficient mineralization can result in rickets and/or osteomalacia. Rickets refers to deficient mineralization at the growth plate, as well as architectural disruption of this structure. Osteomalacia refers to impaired mineralization of the bone matrix. Rickets and osteomalacia usually occur together as long as the growth plates are open; only osteomalacia occurs after the growth plates have fused.
rickets is a nutritional deficiency disease that involves mainly calcium, vitamin d, or phosphate resulting in decreased bone stability and strength, Delayed closure of the fontanelles,Parietal and frontal bossing. Craniotabes (soft skull bones).
Enlargement of the costochondral junction visible as beading along the anterolateral aspects of the chest (the "rachitic rosary") . Formation of Harrison sulcus (or groove),Widening of the wrist and bowing of the distal radius and ulna, Progressive lateral bowing of the femur and tibia and causes defects in teeth.
there is two types of rickets: phosphopenic and calcipenic.
pathogenesis: Growth plate thickness is determined by two opposing processes: o chondrocyte proliferation and hypertrophy on the one hand. o vascular invasion of the growth plate followed by conversion into primary bone spongiosa on the other. • Vascular invasion requires mineralization of the growth plate cartilage and is delayed or prevented by deficiency of calcium or phosphorus growth plate cartilage accumulates and the growth plate thickens. • In addition, the chondrocytes of the growth plate become disorganized, losing their columnar orientation with characteristic expansion of the hypertrophic zone. • In the bone tissue below the growth plate (metaphysis), the mineralization defect leads to the accumulation of osteoid.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Hot Selling Organic intermediates
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
2. INRODUCTION:
• Rickets is a disorder of defective mineralization of the growing
skeleton (before epiphyseal closure), the pediatric counterpart of
osteomalacia(adult form of rickets).
• There is a deficiency of vitamin D that disturbs the calcium and
phosphorus homeostasis and produces the characteristic
manifestations.
• To understand the disorder, it is necessary to understand the
metabolism of calcium and vitamin D in the body.
3. POLPULATION AT RISK
• Children with dark skin (increased melanin)
• Exclusively breastfed for past 06months of age (since breast milk is
poor in vitamin D)
• No vit-D supplementation
4. METABOLISM OF CALCIUM
PHOSPHOROUS AND VITAMIN D
• Vitamin D is synthesized primarily in the body (90%) from 7-
dehydrocholesterol present in the epidermis upon exposure to
sunlight.
• while small amounts (10%) are added by the dietary sources (vitamin
D3 or cholecalciferol from animal sources and vitamin D2 or
ergocalciferol from plant sources).
8. PATHOPHYSIOLOGY OF RICKETS
• The prime pathology in rickets is inadequate mineralization or
calcification of physis (growth plates) in growing bones due to
deficiency of vitamin D.
• Hence, the zone of provisional calcification is inadequately
mineralized and bony trabeculae become weak.
• Under increasing stresses of body weight, the physis gets deformed,
leading to defective growth and bony deformities.
9.
10. SIGN & SYMPTOMS
• Nutritional rickets generally manifests in infants and preschool children.
Generalized features are failure to thrive, muscle weakness, listlessness and
lethargy.
• The child may present with tetany (positive Trousseau or Chvostek sign) or
convulsions because of hypocalcemia.
• Pathological fractures may result due to weak bones.
• Once the patient starts walking, bony deformities may develop like bow
legs (genu varum, most common), knock knees (genu valgum, occurs in
older children), windswept deformity of the legs (varum at one knee and
valgum at the other).
11. Some other classical clinical features are:
• Frontal bossing (thickening of frontal bone), usually evident after the age of
6 months
• Delayed closure of fontanel
• Craniotabes (usually first manifestation): Refers to soft skull bones that can
be pressed like a ping-pong ball
• Delayed dentition
• Broadening of ankle, wrist and knee joints: Due to deformed physis
• Enlarged costochondral junctions (rickets rosary Due to subluxation of the
physis
• Indentation over the lower chest at attachment of diaphragm (Harrison's
sulcus)
• Pot belly: Due to abdominal muscle hypotonia
• Pigeon chest (pectus carinatum}: Refers to a protruding sternum
12.
13. PARADOX OF RICKETS
• As the rickets becomes more severe and the child becomes more
sick,the changes in the epiphyseal plate become milder and may
actually disappear if the patient lives long enough.
• This paradoxical behavior is d/t the fact that rickets, by definition,is a
disease of growth.
• If the patient becomes chronically ill with respiratory,cardiac or renal
diseases , growth is inhibited on a hypoproteinemic or nutritional
basis and the epiphyseal manifestations of rickets fade.
14. RADILOGICAL
FEATURES
• There may be delayed appearance of the
epiphysis.
• The physis is widened due to non-
mineralized osteoid that accumulates in
the area.
• There is no zone of calcification due to
defective mineralization and the area is
filled by irregularly arranged cartilage cells,
so the metaphyseal margins touching the
growth plate look irregular and frayed.
• Due to weight-bearing stresses, the
metaphysis becomes cup-shaped and
splayed (flat and wide). Generalized
osteopenia may be visible and the cortex
may thin out.
• Deformities of bones may be visible in the
later stages.
15. • LOOSER’S ZONES : these are
transverse bands of
unmineralized osteoid, which
typically appear in the aspect
the proximal femur and at the
posterior aspect of ribs
• They are also described as
pseudofractures / milkman’s
line (in adults they can progress
to true fractures).
16. TYPES OF RICKETS & LAB FINDINGS
1) NUTRITIONAL RICKETS
• This is the most common variety in developing countries.
• The recommended daily intake of vitamin D is 400 IU for infants, 600 IU from 1
year to 70 years of age, and 800 IU for those over 70.
• Inability to take these recommended levels leads to dietary deficiency of
vitamin D, so active vitamin D [l,25(0H)2 D] levels are low.
• This leads to inability to absorb calcium and phosphorus.
• PTH is elevated in response to hypocalcemia, corrects the serum calcium, so
calcium levels are normal to low while phosphate levels may be low to normal.
Alkaline phosphatase (ALP) is elevated.
• Cut-off value for vitamin D deficiency: Most investigators have used different
cut-off levels to define vitamin D deficiency .
• Most commonly used cut-off value to define vitamin D deficiency is 25(0H)-
vitamin D less than 20 ng/mL, insufficiency as 20- 29 ng/mL and sufficiency as
more than or equal to 30 ng/ mL. Severe deficiency is defined as a level less
than 5 ng/mL.
17. 2) Vitamin D-dependent Rickets (VDDR)
VDDR-1:
• It is an autosomal recessive disorder due to deficiency of 1-alpha-hydroxylase
renal enzyme.
• It is necessary for the formation of the active metabolite of vitamin D which is not
formed in adequate amount [ 1,25( OH- vitamin D levels low].
• This leads to inability to absorb calcium and phosphorus and levels of both
minerals are low in serum.
• PTH is elevated in response to hypocalcemia.
• ALP is also elevated.
• To differentiate it from nutritional rickets, levels of 25(0H)-vitamin D and
l,25(0H)2 -vitamin are measured. In nutritional variety, both will be low while in
vitamin D-dependent rickets (VDDR) type I, the levels of 25( OH)-vitamin D will be
increased while the active form [l,25(0H)2-vitamin D] will be markedly decreased.
The rachitic features appear early with renal tubular dysfunction.
18. VDDR-2:
• It is vitamin D receptor insensitivity disease due to mutation of VDR
gene.
• End organs are insensitive to l,25(0H)2 -vitamin D, so calcium and
phosphorus cannot be absorbed leading to low levels.
• PTH will be elevated in response to hypocalcemia.
• To differentiate it from VDDR-1, vitamin D metabolite levels are used.
Here, both 25(0H)-vitamin D and l,25(0H)2 -vitamin D would be
elevated to increase calcium absorption as there is no problem in the
metabolic pathway.
• Alopecia is present in association with the rachitic features.
19. 3) Vitamin D-Resistant Rickets (Renal Tubular Rickets)
• This is also known as familial hypophosphatemic rickets.
• Here, the basic abnormality is renal tubules' inability to retain
phosphate. Large amounts of phosphorus are excreted in the urine,
leading to hypophosphatemia
• the calcium levels are however normal.
• Defective mineralization results as both calcium and phosphorus are
needed for mineralization. Since calcium levels are normal, PTH is not
stimulated and its blood levels remain unchanged, so would be the
case with vitamin D metabolites as the metabolic pathway is not
affected. Alkaline phosphatase is elevated.
• The diagnosis is established by documenting a low urinary pH and
decreased urinary calcium and increased levels of urinary
phosphates.
20. • Rachitic features in this type appear early, just after infancy.
• Children lag behind in growth have severely deformed bones, but no
myopathy and no hypocalcemia.
• This situation can occur in renal tubular defects like Fanconi anemia
and renal tubular acidosis where there is a problem with the kidney
to reabsorb phosphorus. In acidosis, the body has to excrete fixed
base, i.e. bicarbonate and calcium phosphate are excreted along.
21. 4) X-linked hypophosphatemic rickets
• It is a genetic disorder with dominant inheritance characterized by
mutations in the phosphate-regulating gene (PHEX gene-having
homology to endopeptidases) present on chromosome X.
• This leads to excessive urinary excretion of phosphate by restricting
the ability of proximal renal tubular brush border to reabsorb
phosphorus and calcium.
22. 5) Renal Osteodystrophy
• It is seen in children who have a chronic renal disease that leads to
renal failure.
• The problem begins with a damaged renal glamorous inability to
excrete phosphorus leading to hyperphosphatemia.
• Because of kidney failure, less of l,25(0H-vitamin D is produced
which eventually leads to hypocalcemia.
• This stimulates PTH and causes secondary hyperparathyroidism.
Increased PTH resorbes calcium from bone in heavy amount, leading
to osteitis fibrosa cystica (multiple cysts in the bone).
• Spine radiograph may show alternate bands of sclerosis and lysis
referred to as the rugger jersey spine
23. • Ectopic calcification can occur due to high phosphate levels.
• Prolonged stimulation of PTH secretion leads to hyperplasia of the
parathyroid glands.
• Parathyroid gland becomes autonomous and insensitive to changes in
calcium, phosphate and vitamin D.
• This causes hypercalcemia and known as tertiary hyperparathyroidism.
• Labs are High serum phosphate level, markedly raised PTH levels and
decreased active vitamin D levels with low urinary calcium and
phosphorus, in the presence of other features of renal failure are
enough to establish the diagnosis.
26. TREATMENT OF RICKETS
• Nutritional rickets may be treated gradually over several months with daily
dose regimen or with a radical approach using high-dose regimens.
• Single-day dose (Stoss therapy) of 15,000 mcg (or 600,000 IU) of vitamin D
is the commonly used highdose regimen. The single-day therapy is easy to
administer and has better compliance.
• The single day high-dose can be given orally or intramuscularly.
• With single day high-dose therapy, radiographic healing becomes visible in
6- 10 days. Single day high-dose therapy is followed by a daily based
maintenance dose of vitamin D.
• Another high-dose regimen is 50,000 IU of vitamin D weekly for 8 weeks
orally followed by a daily maintenance dose.
• High-dose vitamin D may be repeated (after 3 months) if poor compliance
persists.
27.
28. • Calcium intake should be maintained at approximately 1,000 mg/ day (30-75
mg/kg of elemental calcium per day in three divided doses).
• The patient is also advised to take diet rich in calcium-containing foods like fish
oil, egg yolk
• Estimation of serum calcium, phosphorus and serum alkaline phosphatase levels
is recommended 1 month after initiation of therapy.
• To monitor the effect of treatment, ALP levels and 24-hours urinary calcium can
be used, but the best sign to comment on healing in rickets is healing of the
growth plate on X-rays.
• 24 hours urinary excretion of calcium should be in the range of 100-250 mg/24
hours. Lower value indicates persistent vitamin D deficiency.
• Treatment is continued until 24 hours urinary calcium and ALP return to normal.
• Radiological healing is usually evident after 1 month. Usually it takes 1-2 months
for serum 25(0H)-vitamin D levels to normalize and 3-6 months for ALP to return
to normal. In later stages of healing as mineralization proceeds in the provisional
zone of calcification, a white line appears on X-rays, next to the metaphysic,
called the white line of Frankel.
29. • Radiological healing is usually evident after 1 month.
• Usually it takes 1-2 months for serum 25(0H)-vitamin D levels to
normalize and 3-6 months for ALP to return to normal.
• In later stages of healing as mineralization proceeds in the provisional
zone of calcification, a white line appears on X-rays, next to the
metaphysic, called the white line of Frankel.
30. • In VDDR type I, active form of vitamin (calcitriol) has to be given since
1-hydroxylation is defective.
• VDDR type II has end organ insensitivity and requires very large doses
of vitamin D.
• Vitamin D-resistant rickets is treated by treating the underlying
problem along with phosphate administration to correct
hypophosphatemia in association with calcium supplementation.
• Treatment of renal osteodystrophy involves serum phosphate
reduction (dietaiy restriction, use of phosphate binders, calcium salts
and dialysis), use of vitamin D analog and renal replacement therapy.
• Sodium bicarbonate is used to correct acidosis. Cinacalcet, a calcium
receptor sensitiser (calcimimetic) that inhibits PTH release is usually
used in patients on dialysis with advanced disease.
• Parathyroidectomy may be required for tertiaiy hyperparathyroidism.