Bone, Muscle Joint Basics. Primary Function of Bones 1. 2. 3.
Bone Care Basics (CRF)
-
Upload
andre-garcia -
Category
Health & Medicine
-
view
2.155 -
download
2
description
Transcript of Bone Care Basics (CRF)
2
Course Outline
Chapter 1 Kidney and Hormone Function
Chapter 2 SHPT and Chronic Kidney Failure
Chapter 3 Bone Basics
Chapter 4 Vitamin D Treatment for SHPT
Appendix
3
Chapter 1 Outline: Kidney and Hormone Function
Kidney function and hormone production
Vitamin D hormone: receptors and function
Parathyroid feedback mechanism
Vitamin D hormone, PTH and kidney failure
PTH, SHPT and mortality
4
Kidney Function
Excretion Excess fluid
Mineral balance
• Calcium, phosphorus, potassium, sodium, chloride
Metabolic toxins
• BUN, creatinine
5
Kidney Function
Endocrine Erythropoeitin - stimulates
blood cell production
Renin-angiotension - blood pressure control
D hormone - • Calcium/phosphorus balance and bone
metabolism
• Effect on various other organs with vitamin D hormone receptors (VDR)
6
Vitamin D Hormone Receptors (VDR)
A protein located in the nucleus of the cell
Active D hormone must bind to the VDR, stimulate the VDR, so an action can take place on the target tissue
Active D hormone stimulates the VDR on the parathyroid gland to cease production of PTH
7
Ca2+
PO4
Intestine
PO4
Ca2+
Kidney
D hormone
Blood Ca2+
(& PO4)
Bone
Osteoclast
XParathyroid Gland
8
Reproductive Organs
Kidneys
Intestines
Bones
Immune System
Skin
Bone Marrow
Pancreas
Parathyroid Glands
Vitamin D Receptors (VDR) are Spread Throughout the Body
9
Kidney Failure Mortality Rates
2001 USRDS Annual Report
10
Kidney Failure Mortality Rates
2001 USRDS Annual Report
11
PTH is Directly Related to Mortality
Relative Risk of Death vs. PTH levels(Analysis of 40,000 patients)
0.60
0.70
0.80
0.90
1.00
1.10
1.20
1.30
<50 50–100 100–150 150–300 300–600 600–900 900–1200 >1200
PTH levels (pg/mL)
RR
RR
Chertow et al, ASN Renal Week Abstracts
12
Chapter 1 Review Questions
1. What are some of the actions D hormone is responsible for?
a. PTH suppression and bone mineralization
b. Adequate hemoglobin production
c. Good potassium and phosphorus balance
d. Adequate hydration
2. D hormone deficiency contributes to what?
a. Anemia of chronic disease
b. Autoimmune disorders and hepatitis
c. Secondary hyperparathyroidism
d. Lymphogenesis
13
Chapter 1 Review Answers
1. What are some of the actions D hormone is responsible for?
a. PTH suppression and bone mineralization
2. D hormone deficiency contributes to what?
c. Secondary hyperparathyroidism
14
Chapter 2 Outline: SHPT and Chronic Kidney Failure
Causes of SHPT
Progression of SHPT
Effects of SHPT
15
Causes of SHPT in Chronic Kidney Failure
D hormone deficiency
Hypocalcemia
Phosphorus retention
Acid-Base balance
Diminished degradation of PTH by kidney
Autonomous parathyroid nodules
16
When SHPT Begins
Martinez I, Saracho R, Montenegro J, Llach F: A deficit of calcitriol synthesis may not be the initial factor in the pathogenesis of secondary hyperparathyroidism. Nephrol Dial Transplant 11 Suppl 3:22-28, 1996.
17
Normal Parathyroid Gland Physiology
Make, store and release parathyroid hormone
Regulate serum calcium, D hormone and phosphorus levels
Vitamin D receptors (VDR) and calcium receptors are present on the parathyroid gland and help regulate parathyroid hormone production
18
Progression of Parathyroid Gland Pathology with CKD
Hypertrophy Hyperplasia
Diffuse Nodular
Down-regulation of vitamin D receptors (VDR) Decreased D hormone levels Low dietary calcium Hypocalcemia Increasingly non-responsive to calcium and D
hormone levels
19
Bro S, Olgaard K. Effects of Excess PTH on Nonclassical Target Organs. AJKD 1997.
Side Effects of Elevated PTH
Cardiovascular Left ventricular hypertrophy
Myocardial fibrosis
Hypertension
Calcification in the cardiac and peripheral vascular systems
Immune dysfunction
20
Side Effects of Elevated PTH
Extraosseous calcifications “calciphylaxis”
Pruritis
Bone pain and fractures/altered bone metabolism
Pain and swelling in and around joints
Muscle weakness
Spontaneous tendon rupture
Bro S, Olgaard K. Effects of Excess PTH on Nonclassical Target Organs. AJKD 1997.
21
Side Effects of Elevated PTH
Corneal-conjunctival calcification
Skeletal deformities, retardation of growth
Anemia
Impotence
Altered platelet function
Insulin resistanceBro S, Olgaard K. Effects of Excess PTH on Nonclassical Target Organs. AJKD 1997.
22
Electron Beam Computed Tomography (EBCT) Scan
New noninvasive tool
Allows highly sensitive quantification of calcium deposits in living patients
Allows earlier diagnosis of calcification
Can be used for whole body scanning
23
Yellow indicates calcium deposition
Slide courtesy of P. Raggi.
EBCT Scans Reveal Coronary Artery Calcification in a Dialysis Patient
Bone
24
Mitral Valve Calcification in a Dialysis Patient
Scan courtesy of P. Raggi.
25
Sanders C, et al. Am J Roentgenol. 1987;149:881-887.Kuzela DC, et al. Am J Pathol. 1977;86:403-424.
Slide courtesy of E. Slatopolsky.
CalcifiedNoncalcified
Calcification of the Lung
26Slide courtesy of H. Malluche.
Cutaneous/Subcutaneous Calcification
27
Chapter 2 Review Question
1. Why is an elevated PTH a concern?
a. It leads to bone disease.
b. It leads to cardiac disease.
c. It causes immunosuppression.
d. All of the above
28
Chapter 2 Review Answer
1. Why is an elevated PTH a concern?
d. All of the above
29
Chapter 3 Outline: Bone Basics
Bone function
Bone cell types
D hormone and bone remodeling
Bone turnover and renal bone disease
30
Bone Function
Support and movement of the body
Protection of internal organs
Mineral storage
Production of blood cells
31
Bone
Bone-lining cells Osteoblasts
Osteoclasts Osteocytes
32
Bone
33
Osteoblasts
Small, bone-builder cells that secrete collagen fibers
Precipitate calcium and phosphorus from the blood to mineralize the bones, the creation of the osteocyte
Located at sites where bone remodeling needs to occur
34
Osteoblasts
Affected by elevated PTH levels and D hormone deficiency
Osteoblast activity can be indirectly measured by alkaline phosphatase
35
Osteocytes
Mature bone cells - mature osteoblasts that are embedded in the bone matrix
No longer able to form bone actively
Maintain bone matrix
Play an active role in releasing calcium into the blood
36
Osteoclasts
Large, irregularly shaped, multinuclear cells that consume bone with enzymes
By digesting collagen and releasing bone minerals into the bloodstream, osteoclasts erode the bone surface causing small shallow pits or cavities, which are named Howship’s lacunae
37
Osteoclasts
Activity is increased by PTH, D hormone, and thyroid hormone
Many other local growth factors play an important role in bone remodeling Calcitonin inhibits the release of calcium from
bone D hormone increases intestinal absorption of
calcium PTH and prolactin stimulte D hormone production Interleukin-6 stimulates osteoclast development Estrogen inhibits bone resorption
38
Bone Turnover
A term used to describe the interaction between various hormones and bone formation and resorption
“High Bone Turnover” vs “Low Bone Turnover” disease High Bone Turnover results in a decrease in bone
density with porous and coarse-fibered bone
Low Bone Turnover results in non-uniform bone remodeling
39
Role of D Hormone in Bone Remodeling
D hormone stimulates formation of osteoblasts from osteoprogenitor cells
Activation of D hormone receptor on osteoblast enhances synthesis of osteocalcin, a requirement for new bone formation
D hormone may also indirectly stimulate osteoclast activity
40
Development of Renal Bone Disease
GFR
D hormone metabolism
Plasma HPO4
Ca++ absorption from GI tract
Plasma Ca++
PTH
osteoclasts
Ca++ & HPO4– resorbed from bones
OSTEODYSTROPHIES CaHPO4 product
METASTATIC CALCIFICATIONS Core Curriculum for Nephrology Nurses, 1998
41
Renal Osteodystrophy
42
Effects of SHPT on Bone
Increases osteoclast activity increasing bone resorption
Increase bone weakness and pain
Increase fracture rate
43
Chapter 3 Review Question
1. What are the two categories of bone disease we see in renal patients and what typically is the PTH level?
a. High turnover bone disease with a low PTH and Low turnover bone disease with a low PTH
b. Low turnover bone disease with a low PTH and renal osteodystrophy with an elevated PTH
c. Osteitis fibrosa with a low PTH and adynamic bone disease with an elevated PTH
d. High turnover bone disease with an elevated PTH and low turnover bone disease with a low PTH
44
Chapter 3 Review Answer
1. What are the two categories of bone disease we see in renal patients and what typically is the PTH level?
d. High turnover bone disease with an elevated PTH and low turnover bone disease with a low PTH
45
Chapter 4 Outline: Vitamin D Hormone Treatment for SHPT
Treatment option for SHPT
Pharmacokinetic profiles
Effective treatment modalities
46
*2001 USRDS Annual Report
Percentage of New Chronic Dialysis Patients Treated with D Hormone Therapy*
-D (30)
+D (70)
Treated withD hormone
-D (32)
+D (68)
Hemodialysis Patients Peritoneal Dialysis Patients
47
Treatment Option for SHPT – Vitamin D Hormone Therapy
Calcitriol Rocaltrol® - Oral
Calcijex® - Injectable
Calcitriol (generic) – Oral and Injectable
Doxercalciferol Hectorol® - Oral and Injectable
Paracalcitol Zemplar™ - Injectable
48
Treatment Option for SHPT IV Vitamin D Hormone Therapy*
Hectorol®
doxercalciferol
Zemplar®
paricalcitol
Calcijex®
calcitriol
Half-Life (hr) 32-37 16±9 19±3
Time to max conc.
8-9 hours 5 minutes 5 minutes
Elimination Hepatic Hepatic Hepatic
Protein Binding High High High
Removed by HD?
NO NO NO
*No Clinical Significance*No Clinical Significance
49
Summary
The development of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease begins early in the disease process and has an impact on mortality and morbidity
Bone disease has a large impact on chronic kidney failure patients
Vitamin D hormone therapy is recommended for the treatment of SHPT in chronic renal failure patients on dialysis