Module 6: Bone: Osteoporosis, PTH, Rickets Flashcards Preview

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Flashcards in Module 6: Bone: Osteoporosis, PTH, Rickets Deck (39):

First lets start off with the basics of bone, what process is involved in the maturation and activation of osteoclasts?

RANKL on surface of osteoblasts binds RANK receptor on osteoclast


RANKL (on osteoblasts) is upregulated by what?

Vit D3
Some malignancies


What is secreted by osteoblasts and inhibits the RANKL-RANK interaction?

Osteoprotegrin (OPG)


There are two different mutations associations with Mesenchymal Condensation, the first is mutation in HOXD13, what does this lead to?

Synpolydactyly (extra digit between the 3rd and 4th finger with some degree of fusion)


The second mutation of mesenchymal condensation is RUNX2 (CBFA1), what does this lead to?

Cleidocranial dysplasia (open fontanelles, delayed closure of cranial sutures, primitive clavicles, delayed eruption of secondary teeth)


These cards follow the order of Oke and not class. The first pathology to discuss is Osteoporosis. What is the etiology?

Most commonly seen in elderly or
post menopausal women
--white and thin
--due to a lack of estrogen and thin b.c again less estrogen then obese


What is seen on slide 4, gross image?

Pic to left: normal vertebral body with vertical and horizontal lines and normal height
Pic to right: spinal vertebral body
--destruction of trabecular bone
--destroys horizontal trabeculae --- compression fracture --- loss of height and strength


What is the pathogenesis for osteoporosis?

Lack of estrogen --- activation of T cells in the bone marrow --- makes IL-6,IL-1,TNF alpha --- activates osteoclasts -- thinning of bone
makes IL-7 --- premature apoptosis of osteoblasts ---thinning of bone


What bones are fractured most often in osteoporosis?

Lumbar and Thoracic Spine (Compression fractures of the spine)
Distal forearm: ulnar and distal radius -- colles fracture (falling on an outstretched hand)
Femur (neck)


What are the symptoms in a patient with osteoporosis?

Asymptomatic: incidental finding on DEXA scan (Bone density scan)


What investigations are done for osteoporosis?

DEXA scan: measure bone density should be done on post menopausal women over 60
X-ray: is not done b.c it is not sensitive (only finds late stages or pathological fractures)
Blood: Ca, PTH, PO4, and ALP: all normal because its a slow chronic process
Biopsy: thinning of bony trabeculae and because they are older there will be hypocellular marrow (So more fat cells)


What are the complications associated with osteoporosis?

1.Pathological fractures: horizontal trabeculae are lost --- compression fractures
2. Colles Fracture
3. Femoral Neck Fracture (most common)
4. Fat Embolism Syndrome: 1-3 days post fracture -- FA damaging the endothelium
5. Bed ridden --- stasis--- DVT --PE (COD)
6. Bed Ridden -- pressure ulcers -- secondary infection by S. Aureus
7. Hospital acquired pneumonia


What is secondary osteoporosis due to?

Hyper PTH
Vit D or C deficiency


Moving on to the next topic of bone is Hyperparathyroidism. There are three types primary, secondary and tertiary. First we will tackle primary. what is the etiology?

Most common: solitary parathyroid gland adenoma (aka 1 gland)
Parathyroid Hyperplasia ( 4 glands)
--making PTH without negative feedback


In regards to primary hyper PTH there is sporadic and familial. What are some aspects of each

Sporadic: more common in older ppl
familial: young persons and part of MEN1 and MEN 2A (RET mutation)


What is the general role of PTH?

1.activates osteoblasts first then osteoclasts
--receptors for PTH are on osteoblasts
--so initially you are forming bone and you need angiogenesis for this
2.acts on kidney (distal tubule): reabsorption of Ca2+ and excretion of PO4 and facilitates 1 hydroxylation of vit D ---- calcitriol (active vit D) --- GI to increased intestinal Ca/PO4 absorption


Now that we know the general role of PTH, what happens in primary hyper PTH in the bone?

Increased PTH ---- acts of osteoblasts ---- increased interaction between RANK and RANKL (therefore increased activity of both osteoclasts and blasts) --- activates osteoclasts (derived from monocytes) --- demineralization of bone -- lose calcium and phosphate from bone


What happens in primary hyper PTH in the kidney and tubules?

PTH acts on kidney --- 1-hydroxylation of vit D --- active vit D causes intestinal absorption of calcium and phosphate
PTH acts at the distal tubule --- re absorption of calcium and excretion of phosphate


What are the various blood levels for hyper PTH primary?

High PTH, Ca, ALP (measure of osteoblastic activity)
Low PO4 (b/c kidneys are excreting phosphate)


What is the presentation for hyper PTH primary?

--incidental findings of hypercalcemia on routine blood test
--most common cause of hypercalcemia in patients not hospitalized (hops is neoplasmas)
(What else does Hypercalcemia? renal cell carcinoma, squamous cell lung cancer, sarcoidosis and multiple myeloma)


What are the complications of hyper PTH?

1. Stones: calcium phosphate stones
2. Bone Pain and fractures
3. Groans: GI pain: High Ca --- increased gastric acid release to duodenum -- multiple duodenal peptic ulcers (can bleed -- melena and iron deficiency anemia)
4. Psychic Overtones: (Depression and anxiety)
5. Polydipsia and Polyuria b.c hypercalcemia causes aquaporin in CD insensitive to ADH --- nephrogenic DI (low K and lithium can also cause nephrogenic DI)
6. High Ca --- activates pancreatic enzymes --- acute pancreatitis
7. Cardiac Arrhythmias (Short QT interval) -- COD


Explain the gross image 7a for hyper PTH

Brown tumor: osteitis fibrosa cystica
--destruction of cortical bone
--cystic spaces containing hemosiderin (analogous to chocolate cysts)
--hemorrhage (old blood) from angiogenesis due to osteoblasts (BV are basically being destroyed by osteoblastic activity)
--masses of osteoclasts filling in area of bone that has been completely resorbed


Explain the histological image 7b for primary hyper PTH

Osteoclasts: multinucleated cells with increased activity
Osteoblasts: mononucleated cells lay down osteiod-new bone (pink stuff)
Osteocyte: super small well differentiated osteoblasts laying down lucuna
--which gets activated first? osteoblasts because thats where the receptors for PTH are


Moving onto secondary hyper PTH, what is the etiology?

Chronic renal failure
--side note most common Hyper PTH


What is the pathogenesis for secondary hyper PTH?

Unable to hydroxylate vit D --- decreased intestinal Ca absorption
High PO4 in blood b.c it cannot be excreted (Excess PO4 mops up Ca2+ in blood --- even lower Ca2+ in blood)
Leads to low Ca2+ --- secondary PTH release


What levels do you find in the blood for secondary hyper PTH?

High PTH, PO4 and ALP
low Ca2+


Finally tertiary hyper PTH, what is the etiology?

Chronic renal failure --- longstanding secondary hyper PTH --- hypercalcemia
Can also happen following renal transplant


What is the pathogenesis for tertiary hyper PTH?

PT glands becomes hyperplastic and not sensitive to negative feedback
-constantly secreting PTH without checking on the levels


What do you find in the blood for patients with tertiary hyper PTH?

All high PTH, Ca2+, PO4 and ALP


Renal Osteodystrophy occurs in secondary hyper PTH, what is the pathogenesis?

Chronic renal failure -- hyperphosphatemia --- hypocalcemia --- secondary increased PTH --- increased osteoclastic activity -- increased bone resorption
--iron and aluminum accumulation in bone prevents further bone deposition


What are complications of renal osteodystrophy?

Growth Retardation


Moving on to the last topic of Rickets and Osteomalacia, both of which are due to Vit D deficiency. First we will discuss Rickets. Who is this seen in and what are the causes?

Seen in kids
--seen in darkly pigmented infants that have been exclusively breast fed (UV light penetration is blocked with darker pigmented skin and breast milk is low in Vit D) so nutritional deficiency
--other causes:
----- liver cirrhosis or failure (no 25-hydroxylation of vit D) (What are other processes in kids that give you cirrhosis? A1AT deficiency and AR polycystic kidney disease)
-----renal failure
----Chronic malabsorption


What is the presentation for patients with RIckets?

Bone are soft --- bowing of long bones (Weight bearing bones)
--frontal bossing and rachitic rosary (osteoid overgrowth along costochondral junction)
--green stick fractures (unilateral break)
pigeon breast deformity (pectus carinatum)


In slide 6 what is seen on X-ray for the child with rickets

X-ray: lots of bowing (genu varum)
--rachitic rosary not pictured


What are the blood levels seen in rickets?

Low Ca2+
--if low: not due to renal failure
---if high: renal failure --- unable to excrete phosphate --- secondary hyper PTH


Osteomalacia is vit D deficiency seen in adults. what are the causes?

Chronic renal failure (renal osteodystrophy)
Liver Cirrhosis
Chronic Malabsorption syndromes (Celiac, crohn's, tropical sprue, whipples, PSC, chronic pancreatitis and primary biliary cirrhosis)
Primary biliary cirrhosis: are not able to emulsify fat so not able to absorb any fat soluble vitamins
Pancreatitis: no lipase ---- no lipids --- unable to absorb fat soluble vitamins


What is seen in the blood levels for patients with osteomalacia?

Low Ca2+
High PTH and ALP
PO4 high or low depending on renal function


Explain the bone marrow biopsy seen in slide 6 for the patient with osteomalacia?

Van Kossa Stain
normal 60:40 mineralized to unmineralized bone
--inorganic (Ca and PO4) = 60%
--organic (type I collagen) = 40%
In rickets and osteomalacia there is not enough Ca in bone: issue with bone mineralization, no trouble with collagen, inorganic is therefore much less than 60%


What is the pathogenesis for osteomalacia and rickets?

Vit D deficiency --- decreased calcium and decreased phosphate ---- unable to mineralize bone
but still laying down osteoid

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