This document discusses calcium homeostasis and hypercalcemia. It notes that approximately 99% of calcium in the body is stored in bones and teeth, with the remaining 1% distributed in the extracellular fluid, intracellular fluid, and soft tissues. Hypercalcemia is defined as a serum calcium level above 10.5 mg/dL. Causes include primary hyperparathyroidism in about 50% of cases of hypercalcemia, as well as malignancy, vitamin D toxicity, hyperthyroidism, and certain genetic conditions. Symptoms range from being mild or absent with mild increases in calcium to severe symptoms like confusion and coma with rapid or large rises in calcium levels.
Magnesium is a very important ion in the body, crucial to over 300 reactions.
Its disorders are underdiagnosed and can help improve healthcare if appropriately treated
Magnesium is a very important ion in the body, crucial to over 300 reactions.
Its disorders are underdiagnosed and can help improve healthcare if appropriately treated
This is a power point presentation titled Hypercalcemia of malignancy. For medical power point, x-rays, CT scans, medical projects or other downloads, visit www.medicaldump.com
Slideshow is from the University of Michigan Medical School's M2 Endocrine sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M2Endo
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
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
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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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2. INTRODUCTION
Approx 1000 to 1200 g calcium present in adult
99.3 % in bone & teeth as hydroxyapatite crystals
0.6% in soft tissues
0.1% in ECF.
3. DISTRIBUTION OF CALCIUM
CALCIUM
ECF ICF
8.5-10.6 mg/dl CYTOPLASMIC FREE
2.25-2.65 mmol//l 50-100 nmol/l
IONIZED
45%
PROTEIN BOUND DIFFUSIBLE
45% ULTRAFILTRABLE
55% COMPLEXED
10%
90% ALBUMIN
10% GLOBULIN
4. Protein binding of calcium
Influenced by pH.
Metabolic acidosis decrease protein binding
increase ionized calcium.
Metabolic alkalosis increase protein binding
decrease ionized calcium.
Fall in pH by o.1 increases serum calcium by 0.1
mmol/L
As ionized form is the active form of calcium, serum
calcium levels should be adjusted for abnormal serum
albumin levels.
5. Corrected calcium
For every 1-g/dL drop in serum albumin below 4
g/dL, measured serum calcium decreases by 0.8
mg/dL.
Corrected calcium = measured Ca+ [0.8x(4-measured
albumin)] (Calcium in mg/dl; albumin in g/dl)
8. INTESTINAL HANDLING OF
CALCIUM
Approx 1000 mg calcium ingested per day.
200 mg absorbed.
Mainly in duodenum & jejunum.
Absorption is both passive and active
Passive : paracellular route, non saturable, 5 %
ingested Ca absorbed by this route.
Active: transcellular: receptor mediated, 25% ingested
Ca absorbed.
13. TRPV5
Member of TRP channel
superfamily.
Has intracellular NH2 &
CHO terminals.
6 trans membrane
segments.
A hydrophobic stretch =
pore forming
region, between
segments 5 & 6
14. TRPV5
• N glycosylated region
• Extracellular Klotho
acts
Phosphorylation
site for PKA & C.
PTH & tissue
kalikrien regulate
TRPV5 function
Required for channel
assembly & protein
protein interaction
15. TRPV5
100 times larger selectivity for calcium, compared to
Na.
Its expression in PM is limited
Present in subcellular location, in intracellular
vesicles.
Expressed on PM on stimulation.
Present in closed and open state. Calcium enters
during open state.
Internalized via dynamin and clathrin dependent
process.
17. DRUGS AFFECTING TRPV5
TACROLIMUS : decreased expression of TRPV5 also of
calbindin D9k : mechanism ?
thus causes hypercalciuria.
Cyclosporine downregulates only
calbindin not TRPV5
18. CALBINDIN D 28k
Vit D dependent calcium binding protein.
High calcium affinity.
Calcium bound to it is shuttled toward basolateral
membrane Ca extrusion systems.
19. Effect of diuretics on renal calcium
handling mTALH
Furosemide:
NA NK
NKCC2 2Cl ATPase • Increases the
K
expression of
TRPV5 &
ROMK calbindin
D28k in DCT
LUMEN + & CNT !!?
CALCIUM CALCIUM
lumen blood
20. Thiazide diuretics
Increase calcium reabsorption.
Mechanism: 2 hypothesis proposed.
First hypothesis : ECF
depletion
Increased water & Na absortion in PCT
Decreased calcium filtrate
driving increased Ca absorption in PCT
21. Second hypothesis: increased NaCa exchanger in BL
membrane of DCT & CNT. Not proved.
23. HYPERCALCEMIA (definition)
Serum calcium > 10.5 mg/dl (>2.5 mmol/l)
Ionized calcium > 5.3 mg/dl (1.3 mmol/L)
Mild :Total ca 10.5-11.9 mg/dl (2.5-3 mmol/l) (i 5.6-8
mg/dl; 1.4-2 mmol/l)
Moderate : Total ca 12-13.9 mg/dl (3-3.5mmol/l)
i ca 8-10 mg/dl (2-2.5 mmol/l)
Severe : Total ca 14-16 mg/dl (3.5-4 mmol/l)
i ca 10-12 mg/dl (2.5-3 mmol/l)
24. Epidemiology
Relatively common disorder
Incidence 1-2 case per 1000 adults.
Higher incidence in South Africa and Scandinavia.
Males > females: difference diminishes with increasing
age.
Hypercalcemia from all cause increase with advancing
age.
25. Causes : • Humoral hypercalcemia of malignancy :
• ◦Primary hyperparathyroidism
increased PTHrP (80%)
Breast CA
Malignancy related : •• ■Solitary adenoma
Osteolytic hypercalcemia from osteoclastic
Lung CA
90%
• ■Generalized hyperplasia
activity and bone resorption surrounding the
RCC
PTH related : • ■Multiplemyeloma
tumor tissue (20%) neoplasia type
Multiple endocrine
• 1Secretion of active vitamin D by some
or type 2A
• Leukemia, lymphoma
lymphomas
• ◦Lithium-related release of PTH
Vit D related : vit D toxicity or granulomatousrare
Ectopic PTH secretion - Very
• Hyperthyroidism PTH
◦Familial cases of high
disorders. • Immobilization (Paget's’
disease)
Related to high bone turnover :
• Thiazides
• Vit A intoxication
Milk alkali syndrome.
Idiopathic infantile hypercalcemia ( Williams
syndrome) increased intestinal calcium absorption.
27. Presentation:
The mnemonic "stones," "bones," "abdominal moans,"
and "psychic groans" describes the constellation of
symptoms and signs of hypercalcemia
The history of hypercalcemia is dependent on its cause
and the sensitivity of the individual to higher calcium
levels.
Mild increase : Rapid rise or severe
Asymptomatic, hypercalcemia have
Or may have recurring dramatic symptoms:
problems like kidney conusion, lethargy, may
stones lead to death
29. PATHOPHYSIOLOGY:
The CNS effects are thought to be due to the direct
depressant effect of hypercalcemia.
Renal effects include nephrolithiasis from the
hypercalciuria.
Distal renal tubular acidosis may be observed, and the
increase in urine pH and hypocitraturia also may
contribute to stone disease.
30. Nephrogenic diabetes insipidus occurs from medullary
calcium deposition and inhibition of aquaporin-2.
Renal function may decrease due to hypercalcemia-
induced renal vasoconstriction or if hypercalcemia is
prolonged calcium deposition (nephrocalcinosis)
and interstitial renal disease.
31. Prolonged hypercalcemia tends to cause high gastrin
levels, which may contribute to peptic ulcer disease
and may lead to pancreatitis or the deposition of
calcium in any soft tissue
33. PRIMARY HYPERPARATHYROIDISM
50% case of hypercalcemia in general population.
Prevalence : 1 %, 2% in post menopausal women.
Peak incidence in 6th decade.
Adenoma : single enlarged parathyroid gland
responsible in 80-85% cases
Hyperplasia : in 10-15% cases. Sporadic or part of MEN
Carcinoma : 0.05-1%
34. PHPTH : PRESENTATION
80 % cases: asymptomatic, diagnosed on routine lab
finding of increased serum calcium
20-25% cases: chronic course with mild or intermittent
hypercalcemia, recurrent renal stones, complication of
nephrolithiasis
5-10% have severe and symptomatic hypercalcemia
and overt osteitis fibrosa cystica; in these patients the
parathyroid tumor is usually large (greater than 5.0 g).
35. The diagnosis of PHPT is established by laboratory
testing showing hypercalcemia, inappropriately
normal or elevated blood levels of
PTH, hypercalciuria, hypophosphatemia,phosphaturia
,and increased urinary excretion of cyclic adenosine
monophosphate
36. Treatment
Parathyroidectomy indicated in all symptomatic
patients.
Asymptomatic patient :
• Serum calcium > 1 mg/dl above normal,
• reduced bone mass (T-score of less than –2.5 at any site),
• GFR of less than 60 mL/min, or
• age younger than 50 years. parathyroidectomy
• Hypercalciuria (>400 mg calcium per 24 hours) is no
longer regarded as an indication for parathyroid
surgery, since hypercalciuria in PHPT was not
established as a risk factor for stone formation.
If none of above things met: annual monitoring of patient
for serum calcium, renal function, BMD
37. Pre operative localization of tumor
Not needed in pt undergoing Sx for 1st time.
Needed in pts with no improvement with prior
Sx, recurrence.
Sestamibi scan : sensitive & most popular technique
USG neck can also be used.
38. Pharmacotherapy:
Indications: patient refuses surgery, or surgery
contraindicated, or pt with asymptomatic
hypercalcemia.
Agents used :
calcimimetic, bisphosphonates, estrogens, SERMS.
39. Familial Hypocalciuric
Hypercalcemia
A rare disease (estimated prevalence of 1 per 78,000)
Autosomal dominant inheritance, high penetrance
Loss-of-function mutations in the CASR gene located
on chromosome arm 3q
Hypercalcemia, and relative hypocalciuria.
The hypercalcemia is typically mild to moderate (10.5
mg/Dl to 12 mg/dL)
Affected patients do not exhibit the typical
complications associated with elevated serum calcium
concentrations.
40. the PTH level is generally “inappropriately normal,”
mild elevations in 15% to 20%
Urinary calcium excretion is not elevated, as would be
expected in hypercalcemia.
The fractional excretion of calcium is usually less than
1%
Hypercalcemia in FHH has a generally benign course
and is resistant to medications, except for some cases
successfully treated with the calcimimetic agent
cinacalcet
41. NEONATAL SEVERE
HYPERPARATHYROIDISM
rare disorder, autosomal recessive,
is often reported in the offspring of consanguineous
FHH parents,
Characterized by severe hyperparathyroid
hyperplasia, elevation of PTH levels, severe
hyperparathyroid bone disease, and elevated
extracellular calcium levels.
Treatment is total parathyroidectomy, followed by
vitamin D and calcium supplementation.
This disease is usually lethal without surgical
intervention.
42. TREATMENT OF HYPERCALCEMIA
Tailored to the degree of hypercalcemia, the clinical
condition, and the underlying cause.
Calcium can be decreased by :
• Increasing renal excretion of calcium
• Incresing movement of calcium into
bone
• Decreasing bone resorption
• Decreasing gi absorption of calcium
• Remoning calcium by other means
43. Patients with mild hypercalcemia (<12 mg/dL) do not
require immediate treatment. They should stop any
medications implicated in causing
hypercalcemia, avoid volume depletion and physical
inactivity, and maintain adequate hydration.
Moderate hypercalcemia (12 to 14 mg/dL), especially if
acute and symptomatic, requires more aggressive
therapy.
Patients with severe hypercalcemia (>14 mg/dL), even
without symptoms, should be treated intensively.
44. Volume Repletion and Loop
Diuretics
Correction of the ECF volume
is the first and the most
important step in the
treatment of severe
hypercalcemia from any
causes.
Volume repletion can lower
calcium concentration by
approximately 1 to 3 mg/dL
by increasing GFR and
decreasing sodium and
calcium reabsorption in
proximal and distal tubules.
45. Once volume expansion is achieved, loop diuretics can
be given concurrently with saline to increase the
calciuresis by blocking the Na+-K+-2Cl– cotransporter
in the TAL.
Dose of 40 to 80 mg every 6 hours, and this treatment
together with saline therapy may decrease serum
calcium concentration by 2 to 4 mg/dL.
46. INHIBITION OF BONE RESORPTION
BISPHOSPHONATES: the agents of choice in the
treatment of mild to severe hypercalcemia, especially
that associated with cancer.
They are pyrophosphate analogs with a high affinity
for hydroxyapatite and inhibit osteoclast function in
areas of high bone turnover.
47.
48. The clinical response takes 48 to 96 hours and is
sustained for up to 3 weeks.
Doses can be repeated after 7 days.
Fever is observed in about one fifth of patients taking
bisphosphonates;
rare side effects include acute renal failure, collapsing
glomerulopathy, and osteonecrosis of the jaw.
The dosage of bisphosphonates should be adjusted in
patients with preexisting kidney disease.
49. CALCITONIN
Effective inhibitor of osteoclast bone resorption.
Rapid action <12 hrs.
Effect is transient, minimal toxicity
Dose: 4-8 U/kg SC Q6-12 hrs
Its role is mainly to provide initial treatment of severe
hypercalcemia while waiting for the more sustained
effect of bisphosphonates to begin.
50.
51. EXTRACORPOREAL REMOVAL
In severely hypercalcemic patients who are
comatose, have ECG changes, have severe renal
failure, or cannot receive aggressive
hydration, hemodialysis with a low- or no-calcium
dialysate is an effective treatment.
Continuous renal replacement therapy can also be
used to treat severe hypercalcemia.
The effect of dialysis is transitory, and it must be
followed by other measures.