ParaThyroid Horomone (PTH)

(it increases Ca2+ in blood by releasing it from bone, increasing absorption in the intestine, & preventing the kidneys from excreting it) 

(compare to calcitonin, which is very important in Ca2+ regulation in children, but not very important in adults)

ParaThyroid Hormone (PTH)

calcitriol (the hormonally active form of vitamin D)

Do the following move Ca2+ from serum to bone, or from bone to serum?

ParaThyroid Hormone (PTH)

calcitonin

calcitriol

ParaThyroid Hormone (PTH): Ca2+ from bone to serum

calcitriol: Ca2+ from bone to serum

calcitonin: Ca2+ from serum to bone

calcitonin increases

PTH (ParaThyroid Hormone) decreases

(mnemonic:  calciTONin TONEs down Ca2+ levels in the blood)

2/3 of bone vasculature consists of vessels located in _________ and vessels that arise from those

1/3 of bone vasculature consists of vessels located in  __________ and vessels that arise from those

2/3 of bone vasculature is from the medullary canal of the bone

1/3 of bone vasculature is in the periosteum

A rod is placed in the medullary canal to stabilize the bone.  How could this negatively affect the health of the bone?

1. a plate requires a large opening, which could lead to infection

2. plate could destroy bone vasculature in the periosteum (1/3 of bone vasculature is in the periosteum)

3. plate could destroy bone stem cells in the periosteum

a scaffold on which bone can grow

(compared to an osteoinductive scaffold, which stimulates bone to grow)

They're osteoconductive--bone can grow on them

they're not osteoinductive.  They don't induce bone growth because they're sterilized, and the sterilization ruins ability to induce bone growth

yes, bone can grow on them & they can induce bone growth

(Unlike allograft bone transplants, autograft transplants are not sterilized before being implanted.  Sterilization destroys the bone's ability to induce bone growth.)

Put the 5 stages of bone fracture healing in order? 

1. Fracture & inflammatory phase

2. formation of granulation tissue (the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds.)

3. Callus formation (Periosteal cells near the fracture and fibroblasts within granulation tissue become chondroblasts & form cartilage to bridge the gap of the fracture—the callus.  Woven bone is deposited in the callus)

4. Lamellar bone deposition (replace woven bone with spongy lamellar bone)

5. Remodeling (osteoclasts gradually eat up spongy lamellar bone in places that would normally have compact bone & replace it with compact lamellar bone)

Advanced age (>40 yo)

Comorbidities (ex., diabetes)

Drugs, such as

NSAIDs (given to people whose bone tends to overgrow after injury)

corticosteroids

smoking

poor nutrition

open fracture with poor blood supply
multiple injuries

infection

nothing. Bone vessels are typically 100% open, so you can't open them any further.

(in fact, if you give a vasodilator, you'll probably dilate vessels in the skin and divert blood away from the bones)

3

(glycine, proline, lysine)

Alpha chains (the building blocks of collagen) consist of repeats of 3 amino acids: proline, lysine, and ______

What is the third amino acid, and why is only that amino acid appropriate for that spot in the chain?

glycine 

Every 3rd amino acid of each strand is in the center of the triple helix—only glycine (no side chain; just a hydrogen) fits

hydroxylated proline & lysine will be de-activated if their iron is oxidized from Fe2+ to Fe3+ (happens if the hydroxylation reaction doesn’t complete properly)

Hydroxylated lysine may be oxidized to form aldehyde or allysine, which react with lysine amino acids on other alpha chains to form cross-linkages within the collagen triple helix, so without vitamin C, there are fewer cross-linkages and collagen is weaker. 

they are hydroxylated (-OH is added)

Hydroxylated lysine may be oxidized to form aldehyde or allysine, which react with lysine amino acids on other alpha chains to form cross-linkages within the collagen triple helix 

Procallagen peptidases

tropocollagen

scurvy

(Lack of vitamin C-->low hydroxylation of lysine-->lack of formation of cross-linkages within collagen-->weak collagen)

collagen (specifically, type 1 collagen)

hydroxyapatite crystals

75% of collagen is bad

COL1A1 is the gene for alpha-1 chains

COL1A2 is the gene for alpha-2 chains

Type I collagen is made of 2 alpha-1 chains & 1 alpha-2 chain.

Possible makeup of collagen in this person (where A1 is good alpha-1 chains & a1 is bad alpha-1 chains): 

P(A1a1A2) = 0.5*0.5*1 = 0.25

P(a1A1A2) = 0.5 *0.5*1=0.25

P(a1a1A2) = 0.5 *0.5 *1 = 0.25

P(A1A1A2) = 0.5 * 0.5 * 1 = 0.25 (good collagen—no problems with alpha-1)

3/4 of type I collagen is bad

vascular

mutation in type III collagen alpha chains (found in skin & vessels) high risk of arterial ruptures

chondroblasts (and then chondrocytes)

(without induction, they differentiate into osteoblasts, and then osteocytes)

osteoblasts (and then osteocytes) 

(with induction by TGF-beta & BMPs, they become chondroblasts, and then chondrocytes)

induction by TGF-beta & Bone Morphogenic Proteins (BMPs)

with induction by TGF-beta & BMPs, MSCs develop into chondroblasts

without induction, they develop into osteoblasts

Does cartilage tissue contain blood vessels?  Lymph vessels?  Nerves?

water

(15% is collage, particularly type 2 collagen, and 10% are proteoglycans, especially aggrecan)

collagen

(particularly type 2 collagen; 75% is water and 10% are proteoglycans, especially aggrecan)

proteoglycans (protein + glycosaminoglycans (GAGs))

(especially aggrecans; 75% is water, and 15% is collagen, especially type 2 collagen)

Hyaline cartilage—most common (articular is a type of hyaline)

elastic collagen—like hyaline, but more elastin fibers--stretchier

fibrocartilage—like a mix of hyaline & fibrous tissue—tougher

aggrecans

(a large proteoglycan that, with collagen II, forms the structure of cartilage)

hyaluronic acid

(note:  the most common proteoglycan is aggrecan; the most common glycosaminoglycan is hyaluronic acid)

Appositional growth of cartilage 

type of growth of mature cartilage when newly-differentiated chondroblasts lay down matrix at perichondrium

(appositional = "side by side" or "next to"

compare to interstitial growth, the other type of growth of mature cartilage, in which older chondroblasts/chondrocytes regenerate matrix from lacunae)

interstitial growth of cartilage 

type of growth of mature cartilage when older chondroblasts/chondrocytes regenerate matrix from lacunae

immovable joints (such as between skull bones)

(lit., "together joint")

slightly moveable joints (ex., teeth in jaw)

(lit., "both sides joint"--that is, it's neither fully immobile like a synarthrosis, nor fully mobile like a diarthrosis)

Diarthrosis

freely moveable joints (synovial joint)

(lit., "between joint")

4 parts of a synovial joint :

__________ (outermost part)

_____________ (lining)

______________(fluid)

_____________ (cartilage)

fibrous capsule (continous with the periosteum of articulating bones)

synovial membrane (lines inside of fibrous capsule; secretes synovial fluid)

Synovial fluid (lubricating fluid that also acts as a shock-absorber and carrier of nutrients for cartilage; thin, watery, & slick like snot)

Articular cartilage on ends of bones

Gliding joint

Hinge joint

one of the 6 types of synovial joints; allows flexion & extension in one plane (like a door hinge)

found between the humerus and ulna in the elbow & in the knee

one of the 6 types of synovial joints; one bone rotates about another

between the ulna & radius in the elbow, between the skull and C1 (the atlas)

Condyloid joint

one of the 6 type of synovial joint; ike a ball & socket, but the “ball” is ovoid or oddly-shaped & fits into a matching “socket”, therefore allowing more limited range of motion than a true ball & socket joint (such as the hip)

found between the radius & the scaphoid bone of the wrist

ball & socket allows a greater range of motion

condyloid is like a ball & socket, but the “ball” is ovoid or oddly-shaped & fits into a matching “socket”. The non-spherical shape limits movement more than true ball & socket  (such as the hip)

condyloid permits movement in two planes, allowing flexion, extension, adduction, abduction, and circumduction (movement in a circle).  There is a condyloid joint between radius & the scaphoid bones of the wrist

Saddle joint

one of the 6 types of synovial joints; like 2 saddles with the convex parts meeting; permits similar movements to a condyloid joint:  flexion, extension, adduction, abduction, and circumduction (movement in a circle)

seen between the tibia and femur in the knee joint

the 2 ball-and-socket joints in the body are hip joints & shoulder joints

What's the difference between tendons & ligaments? 

tendons connect muscle to bone or muscle to structure (ex., eye)

ligaments are one of 3 things:

1. fibrous tissue that connects bone to bone 

2. a fold of the peritoneum or other membrane

3. the remnants of a tubular structure from the fetal life period

the compression of nerves, blood vessels, and muscle within a closed fascial compartment when there is excessive swelling 

end of long bone

(the middle of the long bone is the diaphysis; between the diaphysis and the epiphysis is a thin region called the metaphysis, which contains the growth plate in children)

diaphysis

(lit, "between growth")

(the middle of the long bone is the diaphysis; the end is the epiphysis; between the diaphysis and the epiphysis is a thin region called the metaphysis, which contains the growth plate in children)

a group of related genes that transcribe proteins that regulate segmentation patterns in embryonic development 

(side note:  in flies, hox gene mutations can cause legs where the antennae should be or extra sets of wings; in humans, hox mutations are rare, but hand and foot deformities have been associated with hox mutations)

a signaling molecule that acts directly on cells to govern the pattern of tissue development (esp. the positions of the various specialized cell types within a tissue)

(ex., TGF-beta, sonic hedgehog, etc.) 

note: morphogens are defined by function, not chemically

Binds to receptors that inhibit transcription of osteocalcin in osteoblasts (Osteocalcin is a key extracellular matrix protein that promotes bone mineralization)

Induces osteoblast apoptosis

Increases osteoclast activity

Indirect osteolytic effects through other endocrine mediators of calcium regulation

Biphosphonates slow bone remodeling, but especially bone resoprtion.

They are used to preserve bone mass in people with osteoporosis, osteopenia, or other conditions that cause bone fragility, and also to treat Paget's disease of bone.

A ParaThyroid Hormone (PTH) fragment that has an anabolic effect to replace lost bone density

Teriparatide is, thus far, the only drug that increases bone mass (other drugs slow loss but do not reverse it). 

(PTH increases serum Ca2+, partially accomplishing this by increasing bone resorption. Thus, chronically elevated PTH will deplete bone stores. However, intermittent exposure to PTH will activate osteoblasts more than osteoclasts. Thus, once-daily injections of teriparatide have a net effect of stimulating new bone formation leading to increased bone mineral density.)

must be taken with water after an overnight fast at least 30 min prior to any other food or drink (biphosphonate is polar and not well absorbed, and food makes it worse)

must sit upright for at least 30 minutes after taking (biphosphonate can cause severe esophageal irritation, and esophageal cancer)

Calcitonin is not important for adults. If you take out your thyroid, you have no more calcitonin, which causes no problems (you have to replace the thyroid hormone, but not the calcitonin).

In children, calcitonin is important for building bone.

mnemonic:  calciTONin TONEs down Ca2+ levels in the blood (by storing Ca2+ in the bones)

How does calcitonin's effectiveness compare to biphosphonates at blocking bone resorption?  

When would you take calcitonin? 

less effective

calcitonin can be added to biphosphonate therapy if that alone is note enough.

resorbs calcium & phosphate from the bone if serum calcium & phosphate are low

(if serum Ca2+ and phosphate are NOT low, it won't cause resorption from the bone, but will increase calcium absorption in intestines and retention in kidneys, so give vitamin D to people in danger of bone mass loss)

a localized dysregulation of bone turnover that involves ­ increased bone resorption and ­increased bone formation. Results in formation of bone that is poorly organized, weaker, painful, and deformed.

(The cause may be a combination of genetic factors and viral infection)

fibrillin

(fibrillin a glycoprotein that is the major structural component of extracellular microfibrils.  Microfibrils form a network for elastin deposition, so elastin is also negatively affected.)

when a cell or organism DOESN'T have an integer multiple of the haploid set of chromosomes because of monosomy or trisomy in one or more of the chormosomes.  Monosomy and trisomy are two types of aneuploidy

ex., in humans, the haploid set of chromosomes is 23; the normal diploid set of chromosomes per cell is

2 * 23 = 46

This is euploidy.  Monoploidy, or having 23 chromosomes per cell, and polyploidy, such as having 69 chromosomes per cell (note: polyploidy, unlike aneuploidy, by definition always affects ALL cells in an organism), would also be euploidy but would not be viable in a human embryo. 

when a cell OR organism has an integer multiple of the monoploid set of chromosomes (1n, 2n, 3n, 4n, etc.)

in aneuploidy, the cell or organism does NOT have an integer multiple of the monoploid set of chromosomes b/c of monosomy or trisomy

Polyploidy

when ALL cells in an organism have a loss or gain of a complete haploid set of chromosomes (1n, 3n, 4n, etc.)

 (always lethal to embryo in humans)

Patau's syndrome

(Patau's syndrome causes cycloPism via holoProsencephaly; high risk of fetal death & 80% of children do not survive their first month) 

Edwards syndrome

(Eighteen causes Edwards syndrome--high probability of fetal death; only 5-10% survive their first year) 

Turner (sex chromosome monosomy, X)

(phenotypically female, short, webbed neck, infertile, learning difficulties but usually normal intelligence)

Turner syndrome

(phenotypically female, short, webbed neck, infertile, learning difficulties but usually normal intelligence)

What syndrome is being described? 

Female phenotype

Short stature

Ovarian failure leading to primary amenorrhea & infertility

Coarctation (narrowing) of the aorta

Some renal anomalies

Klinefelter syndrome

(male phenotype, but some more feminine physical characteristics such as less body hair and female-type fat distribution afte puberty; tall; infertile; learning disability but no retardation)

triple X syndrome

(Female phenotype; Fertile; No major congenital anomalies; Slight cognitive impairment; 2 Barr bodies)

What genetic syndrome do these clinical signs describe? 

Female phenotype

Fertile

No major congenital anomalies

Slight cognitive impairment

2 Barr bodies

abnormalities that do not change gene dosage (re-arrange genes, but don’t gain or lose genes)

Translocation leaves the carrier with the same amount and type of genetic material (same gene dosage).  Translocation will often not cause a problem for the carrier (person in which translocation occurs) UNLESS it breaks an important gene in half or moves an important gene relative to regulatory DNA (which changes expression)

But it could lead to unequal sorting in meiosis. The cell with the now-bigger chromosome has partial trisomy. The cell with the now-smaller chromosome has partial monosomy.

when one chromosome is cut & donates a piece to another chromosome; aka non-reciprocal translocation

(in reciprocal translocation, 2 chromosomes are cut and exchange pieces)

a joint that is more than one of the 6 basic types (ex.,knee is hinge & gliding)

(the 6 types are gliding, hinge, pivot, condyloid, saddle, and ball-and-socket joints)

median

ulnar

brachial artery (remember: arm = upper arm)

(this vessel is called the subclavian artery where it branches off from the aorta/brachocephalic artery, renamed the axillary artery in the shoulder, and then renamed the brachial artery in the upper arm) 

children

because their bones are growing and, thus, very well vascularized

in the metaphysis of long bones

because the metaphysis contains the growth plate, which is very well vascularized

A child with a blood-borne disease has

Chills

High fever

Malaise

Local pain around the metaphysis of the femur

Swelling around the metaphysis of the femur

Bone culture is negative

What are you concerned about, and why?  

Osteomyelitis in the metaphysis of the femur.

Bone cultures are negative in 50% of cases of osteomyelitis; the clinical signs and symptoms are consistent with osteomyelitis

Elderly are more prone to:

 pelvic infections

retrograde flow in veins

Theoretically, retrograde flow from pelvic tissues (urethra, prostate, bladder) to lumbar vertebrae can explain the spread of pelvic infections preferentially to lumbar vertebrae.

increases 

because vascular insufficiency prevents the immune system from patrolling as efficiently as normal

Typically polymicrobial with aerobic & anaerobic organisms

Coagulase + staph (ex., staph aureus)

Coagulase neg staph (ex., staph epidermidis)

Strep Enterococcus

Sickle-shaped RBCs cause frequent blood vessel blockages, which leads to small areas of necrosis

Salmonella more easily leaves the gur through necrotic areas

Bones with vascular insufficiency are more easily infected

catalase is an enzyme that turns peroxide into water & oxygen:

H2O2 –(catalase)--> H2O + O2

put the bacteria in peroxide & see if it causes bubbles

abnormal softening/thinning of skull

(seen in Rickets)

soft bones

slightly or moderately bow-legged (not extreme like in rickets)

(osteomalacia is a disease caused by vitamin D deficiency in adults; it's the adult form of rickets)

renal osteodystrophy

there is a failure to keep the proper amount of Ca2+ and phosphorous in the blood, either because the kidneys fail to retain sufficient Ca2+ and phosphorous, or because dialysis clears more Ca2+ and phosphorous from the blood than the kidneys do, (or a combination)

ParaThyroid Hormone (PTH)

small 

Paget's disease of bone

(it probably has both genetic and viral elements, but we don't really know what causes it)

Explain the following mnemonic:

Optochin Outs pneumOnia

Explain the following mnemonic:

Eighteen is Edward's

thirteen starts with a consonant

trisomy 18 causes Edward's syndrome

trisomy 13 causes Patau's syndrome

Explain the following mnemonic

You give to the dread chromosome Roberts.  He gives nothing back to you.

Robertsonian (Non-reciprocal) Translocation is when one chromosome is cut & donates a piece to another chromosome

(vs. reciprocal, when the 2 chromosomes exchange pieces)

Explain the mnemonic: 

Pink turns yellow, kill a fellow

Mannitol Salts Agar is a high-salt agar that only allows the growth of salt-happy bacteria (staph)

It normally appears hot pink, but turns neon yellow in the presence of the more virulent Coagulase-positive staphylococci (such as staph aureus).

What nerve runs down the front of the thigh & innervates the skin on the front of the thigh & knee?

What branch of this nerve innervates the skin on the lateral thigh?

femoral

superficial femoral

What nerve innervates the skin on the medial part of the thigh?

obturator

Is the median or the ulnar nerve affected by carpal tunnel syndrome?

median

the ulnar nerve passes above the carpal tunnel

What nerve innervates the:

Hypothenar muscles

all of the interosseous muscles (abductors & adductors)

third and fourth lumbricals (flex the metacarpophalangeal joints and extend the interphalangeal joints)

the adductor pollicis and

part of the flexor pollicis brevis.

type 1 collagen

(the most abundant collagen in the body)

collagen chains