Quiz 8 Practice Problems Flashcards
Which is the predominant type of collagen found in bone?
type I collagen
type II collagen
type III collagen
type IV collagen
type X collagen
type I collagen
Type I collagen is the principle type of collagen secreted by osteoblasts, it’s also the principle type of collagen found in connective tissue proper.
In developing cartilage, the most mature and differentiated areas are in:
The center of the cartilage.
The inner perichondrium.
The outer perichondrium.
The periphery of the cartilage next to the perichondrium.
The center of the Cartilage
The initial cartilage growth is appositional, as chondroblasts arise in the perichondrium and begin to secrete matrix. Thus, the oldest cartilage will be in the middle and the youngest at the periphery, under the perichondrium.
The blood clot initially forms at the site of a bone fracture is next replaced by:
Hyaline cartilage
Loose connective tissue
Both
Neither
Both:
Fibroblasts, myofibroblasts, osteoblasts, chondroblasts, and other cells invade the clot and begin secreting extracellular matrix. Thus, there is both hyaline cartilage and loose CT present and when that is replaced with bone, both endochondral and intramembranous ossification will be involved.
Compared to the hyaline cartilage in tracheal rings, articular cartilage lacks:
Chondrocytes
GAGs
Hyaluronic acid
Perichondrium
Type II collagen
Perichondrium
Articular cartilage arises from an “interzone” area of mesenchymal cells that forms the joint between two bones. This cartilage lacks a perichondrium, but contains all the other items listed; the lack of perichondrium provides the smooth surface necessary for proper joint function.
Without a perichondrium, articular cartilage lacks the normal source of:
Chondroblasts
Fibroblasts
Lymphatics
Nerve cells
Smooth muscle
Chondroblasts
Technically this is not a good question, as you could make a case for answers a – d being correct. The perichondrium contains fibroblasts, lymphatics, and probably some nerve fibers, but also progenitor cells that can make chondroblasts. The best answer for thinking about cartilage growth and repair is ‘a’ because the perichondrium of other types of permanent cartilage provides the source of chondroblasts for growth and repair. Resident chondrocytes in articular cartilage are responsible for turnover and replacement of damaged areas.
Recently, almost every time you fall off your skateboard, you break a bone. In addition, you have recently developed kidney stones. A biopsy revealed your bones are thinner than normal. What change in cells do you expect to see in this biopsy?
An increased number of osteoclasts
A decreased number of osteoclasts
An increased number of osteoblasts
An increased number of osteocytes
A decreased number of chondrocytes
An Increased number of osteoclasts
A decrease in bone mass is expected to be the result of an imbalance in the activity or numbers of osteoclasts versus osteoblasts, with relative osteoblast activity increasing. This could be due to an increase in osteoclasts or a decrease in osteoblasts. An increase in kidney stones would suggest that osteoclast numbers have increased, since osteoclasts are responsible for increasing serum calcium levels and their numbers are increased by hormonal signaling.
A
Adult bone, whether trabecular or compact, is lamellar.
Fibrocartilage differs from hyaline cartilage because fibrocartilage contains:
A perichondrium
Blood vessels
Large amounts of elastic fibers
Type I collagen
Type II collagen
Type I Collagen
Fibrocartilage, unlike hyaline and elastic cartilage, contains large amounts of type I collagen, though it also contains type II cartilage, as does hyaline cartilage, so that is not a distinction. Fibrocartilage lacks a perichondrium, blood vessels, or a significant number of elastic fibers.
In adult bone the collagen fibers of adjacent lamellae of an osteon are oriented:
Randomly
0 degrees to each other
90 degrees to each other
180 degrees to each other
90 Degrees to each other
Osteoblasts organize collagen fibers orthagonally in adjacent lamellae, which increases the strength of bone.
A researcher is investigating the use of mesenchymal stem cells (MSCs) as a therapy for osteoarthritis (OA), employing a goat model. OA can be induced in a goat’s knee joints by surgically removing the medial meniscus, followed by normal exercise. After surgery, some of the goats received an injection of labeled MSCs suspended in saline into the treated joint, control animals received only the saline. Later analysis reveals that the articular cartilage is significantly less degraded in the goats receiving MSCs. However, in these experiments no MSCs or cells derived from them were detected in the articular cartilage, although a small number of MSCs and MSC-derivatives were found elsewhere in the joint. The most likely explanation for this effect is that the MSCs and their few derivatives found in the joint are producing:
Chondronectin
Cytokines
Hyaluronic acid
Matrix metalloproteinases
Type II collagen
cytokines
Since it is known that the behavior of chondrocytes is influenced by a number of cytokines and that a perturbation in these signals is likely to be involved in OA, the production of cytokines by MSCs is the most likely explanation for this result. The cytokines could be acting both on chondrocytes in the articular cartilage as well as on other cells in the joint to ameliorate the normally destructive series of events that produces OA. It is unlikely that the production of matrix components by a small number of MSCs outside of the articular cartilage would have any significant beneficial effect and increased production of protease by hypertrophic chondrocytes is known to be involved in the progression of OA
Hyaline cartilage differs from bone because it:
Contains Type I collagen fibers
Contains Type II collagen fibrils
Is composed of cells surrounded by fibers and matrix
Is covered by a layer of connective tissue
Is richly vascularized
Contains Type II collagen fibrils
The unique feature for cartilage on the list is the presence of type II collagen. In fact, type II collagen is only found in significant amounts in cartilage and one other place in the body; where do you think that is?: type II collagen is also found in the vitreous humor of the eye. Mature bone will only contain type I collagen, produced by osteoblasts. Both bone and cartilage is composed of cells surrounded by matrix and both can be covered with a layer of connective tissue. Hyaline cartilage is not directly vascularized.
Vitamin C is required for the proper assembly of collagen fibers due to its participation in:
Glycosylation reactions in the Golgi
mRNA processing
Peptide transport into the RER
Redox reactions
Vesicle transport from RER to Golgi
Redox Reactions:
Vitamin C is required for the redox reactions that result in the hydroxylation of proline and lysine residues on collagen.
Bone remodeling often does not occur normally in:
Adolescents prior to the closure of the epiphyseal growth plate
Adults after the closure of the epiphyseal growth plate
Newborns until they reach 6 months
Post-menopausal women
Post-menopausal women
The ability of osteoblasts to replace bone removed by osteoclasts during normal bone remodeling declines with increasing age; this is called senescent osteoporosis. This is seen more frequently in women after menopause. Remodeling is expected to occur normally in the other cases.
B
The cells most active in the synthesis and secretion of osteoid are:
Osteoprogenitor cells
Osteoblasts
Osteocytes
Osteoclasts
Bone-lining cells
osteoblasts
Osteoblasts responsible for the synthesis of the bulk of osteoid and its mineralization. Those trapped in the matrix they are called osteocytes, which are then responsible for maintenance of bone.
An 8-year-old girl is seen in clinic because her parents are concerned about her lack of growth. Bone scans reveal that her epiphyseal growth plates are beginning to close prematurely. To slow the closure of the growth plate and to promote continued growth of her long bones, her pediatrician prescribes somatotropin (growth hormone) in order to:
Stimulate the hypertrophy of chondrocytes in the growth plate
Stimulate the maturation of osteoblasts to osteocytes
Stimulate the deposition of osteoid at the growth plate
Stimulate proliferation of chondrocytes in the growth plate
Stimulate the deposition of hydroxyapatite in the osteoid at the growth plate
Stimulate proliferation of chondrocytes in the growth plate
Somatotropin is responsible for stimulating mitotic activity of chondrocytes in growth plate cartilage until late adolescence when growth stops.
A 9-year-old boy is seen in the ED for a fractured rib that resulted from a minor fall. On X-ray, his bones appear unusually dense and additional imaging studies reveal that his bone marrow cavities are smaller than expected. A defect in what cell type is most likely responsible for this condition?
Chondroblasts
Chondrocytes
Osteoblasts
Osteoclasts
Osteocytes
Osteoclasts
This is a description of osteopetrosis, also called marble bone disease. It is due to a failure of osteoclasts to resorb bone at a normal rate. As a consequence, marrow cavities become smaller as they are filled in with bone. Although bones in this case are denser, they are not stronger, likely because of reduced bone remodeling: turnover and replacement of old bone with new. There are several forms of this disease, all of which appear to be caused by mutations in genes important for osteoclast activities.
1.. Individuals are shown with hand defects consistent with abnormal Shh function. Discuss what kind of disruption of Shh expression/function may have occurred in each of the four cases shown and what other disorders you may want to screen for in each of these individuals.
- Interpreting defects is something of an art, and therefore open to more than one possible answer. However, the general concepts should be similar for all interpretations. Cases with a triphalangial digit in the position of the thumb (cases 1, 2 and 4) would appear to be a transformation of this digit to a more caudal digit, suggesting excess Shh signaling or aberrant Hox-patterning of the limb bud. In addition, case 4 looks very similar to experimental duplication of the ZPA on the cranial margin of the limb bud—so this could be the case here as well. Case 3 (duplication of the caudal most digit) is curious—suggesting increased size of the ZPA in its normal location.
. Craniofacial stenosis syndromes caused by defective Fgf signaling are often associated with “sock foot deformity” (see image). Discuss how this condition arose during development (what molecular pathways and cellular events were perturbed). How might altered Fgf signaling interact with the known molecular pathways regulating digit formation. (This may require you to learn something about the role of Fgf in these processes on your own.)
As noted in the craniofacial lecture, foot and hand deformities are common in cases of craniofacial stenosis associated with excess Fgf signaling. The “sock foot deformity” strongly suggests there has been a failure of programmed cell death in these individuals. Although regulation of cell death is complex, substantial evidence suggests Fgf signaling inhibits BMP-mediated cell death. During limb development, Fgfs from the AER maintain the progress zone and induce proliferation of cells in an undifferentiated state. This strongly suggests that part of why syndactyly is seen in individuals with increased Fgf signaling is overproliferation of immature cells in the interdigit region. Fgf signaling may also act to directly inhibit BMP or to stimulate Wnt signaling, thereby preventing cell death.
. Patients with Marfan syndrome are very tall, with an arm-span greater than their height, hypermobile joints and long digits (see diagram). This syndrome is due to a defect in Fibrillin-1 that results in excels Tgf-beta signaling and an alteration in the function of mesenchymal stem cells (MSC) in the bone marrow (see diagram). Based on this pathway, discuss the impact of the Fibrillin-1 mutations on bone formation and resorbtion, and relate it to the Marfan phenotype.
The most likely interpretation of the effect of Fibrillin-1 defects is an imbalance favoring bone decreased bone mass (see below). This would be consistent some (but not all) aspects of the Marfan phenotype. The balance of bone growth to clearly changes over the life span—with Marfan patients showing increasingly fragile bones as they age. Interestingly, the most medically critical aspect of this syndrome has to do with the structural role of Fibrillin 1 in the assembly of elastin fibers. Marfan patients have enlarged aortae, due to a weak vascular wall, and are at increased risk for aortic rupture.
The following procedure (Dorsal flexion) is performed during the MSK portion of a PE. Identify the following:
Muscles
Myotome
Nerve
Compartment
D
B
D
From the micrograph, it would appear that the hair corresponds to the stratum corneum, as there seems to be a separate stratum granulosum layer in the surrounding epithelial sheath. However, some texts state that there are contributions from the stratum granulosum in hair, so both b and c could be true. This was mostly an exercise to get you to look at the epidermal layers in a different orientation.
Given the following arterial values, calculate the patient’s arterial pH.
a. 7.32
b. 7.60
c. 6.90
d. 7.40
a. 7.32
A patient has the following arterial blood values.
Which of the following is the most likely explanation for the values. Choose the one
correct answer.
a. The patient has a primary (before compensation) respiratory acidosis.
b. The patient has a primary respiratory alkalosis.
c. The patient has a primary metabolic acidosis.
d. The patient has a primary metabolic alkalosis.
b. The patient has a primary respiratory alkalosis.
A 17 year-old boy is brought to the emergency department by a group of his friends after ingesting a number of “purple hearts” (aka Phenobarbital). He is unconscious with a HR 47, RR 7, BP 72/38, and T 35.5. The emergency department staff initiate supportive care by securing his airway with an endotracheal tube, placing large bore IV’s, and beginning fluid resuscitation. What could be done to speed the elimination of phenobarbital (a weak acid with a pKa=7.2)?
Reabsorption in DCT of kidney is passive and charged drugs will be excreted. (harder for polar to diffuse anywhere!) So making the environment so that the weak acid will be charged by making the environment of the urine more basic will lead to more excretion!
A 69 year-old woman with coronary artery disease not amenable to surgical or percutaneous coronary intervention is prescribed nitroglycerin, a coronary artery vasodilator, for the management of her angina symptoms. In follow-up two weeks later, she reports that the nitroglycerin does not seem to be working. Further questioning reveals that she has been swallowing the nitroglycerin tablets that are intended for sublingual administration. What is the most likely reason for treatment failure?
Bioavailability as well as the Rates of Absorption, Distribution, and Elimination may impact clinical drug effects. (e.g. gentamycin exhibits concentration dependent killing and time dependent toxicity)
Administration of drugs by unintended routes may alter the clinical effects.
This patient has been incorrectly taking her nitroglycerin by mouth; the drug is subject to extensive first-pass
hepatic metabolism. The intended sublingual administration route bypasses first-pass metabolism.
A 63 year-old man with chronic renal insufficiency has infective endocarditis of his mechanical prosthetic mitral valve. The causative organism is methicillin-resistant S. aureus and prolonged vancomycin antibiotic therapy is indicated. Vancomycin is eliminated as unchanged drug primarily by glomerular filtration. How should the vancomycin dosing be adjusted to account for this patient’s renal insufficiency?
Protein bound drugs will remain in the plasma…
Impaired renal function may necessitate dosing adjustments for renally eliminated drugs that have toxicities. This may involve adjustments to the maintenance dose and/or dosing interval to decrease the ‘rate of drug in’ to match the diminished ‘rate of drug out’.
Cumulative exposure toxicities may occur with some drugs (e.g. gentamicin, doxorubicin, bleomycin).
Vancomycin exhibits time-dependent microbial killing. It is associated with ‘red man syndrome,’ ototoxicity, and nephrotoxicity.
A 41 year-old woman with a history of depression is being evaluated in the emergency department 6 hours after an apparent suicide attempt with ingestion of approximately 45 regular-strength acetaminophen tablets. Acetaminophen is eliminated from the body by renal excretion of the three non-toxic metabolites depicted in the figure at the right. How could potential hepatotoxicity be diminished or prevented?
The patient in this case has consumed excessive acetaminophen such that the normal primary routes of elimination through Phase II glucuronidation and sulfation are exhibiting zero-order elimination with an increase in Phase I CYP450 metabolism to a reactive intermediate called N-acetyl-p-benzoquinone imine (NAPQI).
This NAPQI intermediate may then be conjugated by glutathione to a non-toxic mercaptopuric acid conjugate. If glutathione stores are depleted, the NAPQI reacts with hepatic enzymes and causes hepatocyte damage.
Administration of N-acetylcysteine increases acetaminophen detoxification by increasing glutathione synthesis and/or acting as a glutathione substitute.
A 63 year-old woman who takes warfarin for chronic atrial fibrillation requires a statin lipid lowering agent due to persistently elevated cholesterol. After two weeks of therapy with fluvastatin she develops a large bruise after accidently striking a door frame. How can this be explained? What should be done? (adapted from Sandsen. Drug-Drug Interaction Primer. 2007)
The patient appears to be experiencing increased anticoagulant effects from her warfarin coincident with starting fluvastatin.
Warfarin is eliminated by hepatic metabolism (predominantly P450 enzymes) and renal excretion of inactive metabolites. CYP2C9 is primarily responsible for warfarin’s S-enantiomer metabolism; the S-enantiomer is 2- 5X more potent than the R-enantiomer.
Fluvastatin is eliminated by hepatic metabolism (predominantly CYP2C9) and fecal excretion.
If fluvastatin is continued, close monitoring and warfarin dose adjustments may be required. Alternatively, fluvastatin could be switched to pravastatin which is not metabolized by P-450.
How do I know the ration of protonated vs. unprotonated form of my drug?
