CAT2 minor internal medicine: week 9 t/m 16 - Lotte Penning

endocrinology and bone, transgender medicine, 1/2 acute internal medicine and 1/2 pharmacology.

What are possible symptoms of hypocalciemia?

SPASMODIC

• s = spasm

• p = perioral paraesthesia

• a = anxious / irritable

• s = seizures

• m = muscle tone increased

• o = orientation impaired / confused

• d = dermatitis

• i = impetigo herpitiformis

• c = chvostek sign or trusseau’s sign

Please explain the chvostek sign

when gently tapping someones cheek in front of their ear the facial muscles twitch.

Please explain the trousseau’s sign

When increasing pressure on the upper arm a carpopedal spasm of the hand occures.

What changes in an ECG in hypocalciemia?

• prolonged QT interval

• narrowing of the QRS complex

• t-wave flattening

• ST-depression

Why should albumin levels be tested when checking calcium levels.

Around half of the calcium that is not stored in bones is binded to protein. When binded it is inactive. When the albumin concentration is known the calcium concentration can be corrected.

Effect of PTH on kidney

• increased excretion of phosphate

• increased reabsorption of calcium

• increased activation of vitamin D

Effect of PTH on insestine

• increased uptake of calcium

• increased uptake of phosphate

Effect of PTH on bones

• increased osteoclast

• increased bone resorption

• activates osteoblast

• more calcium in the blood

What could cause a higher concentration of albumin

dehydration

What could cause a lower concentration of albumin?

• liver disease

• nephrotic syndrom

• pregnancy

• protein losing enteropahty

Effects of low magnesium

• inhibits PTH secretion

• increases cellulair resistance to PTH

DD for hypocalciemia if PTH is low

to better understand. If calcium is low we expect PTH to be high. Since it is not there is a problem revolving PTH/parathyroidglands.

• post surgery

• post radiation

• infiltration

• congenital

• hypomagnesium

DD for hypocalciemia if PTH is high

PTH should be high when there is hypocalciemia. The central problem is thus not related to PTH-respons or production:

• decreased vitamin D

• malabsorption

• vitamin D resistance

• kidney disease

• liver disease

• PTH resistance

What are the effect of thiazidediuretics on calcium levels.

Thiazidediuretics inhibit the reabsorption of Na/Cl. The Na-concentration intracellulair decreases. To compensate this the Na+ / Ca2+ exchange is more activated. Resulting in an increase of intracellulair Na and a increase in Ca-concentration in the blood.

—> increased calcium reabsorption

What is the histological difference between cortical and trabecular bone?

cortical bone had osteon with cirkels around them and trabecular bone is the structure on the osteoporosis pictures

What are the two ways to form bone?

intramembranous and enchondral

Explain intramembranous bone development

mesenchymal stem cells —> osteoprogenitor cells

—>osteoblast. Osteoblast surround matrix, matrix calcifies, development of periosteum and spongybone and compact bone

explain enchondral bone tissue production

cartilage models mineralise matrix, invasion of internal cavities with blood vessels, leaving a epiphysial plate allowing growth.

5 fases of bone turnover

1. activation

2. resorption

3. reversal

4. formation

5. termination

op welke 4 manier zou je botziekte kunnen indelen?

1. disfunctional bone cells

2. disbalans in bone turnover

3. increased bone turnover

4. mieralisation disorder

What is the effect of PTH on phosphate ?

increased excretion through the kidneys and increased phosphate release through the bones resting in netto no changes in phosphate concentration

What does FGF23 do with the phosphate concentration

increases excretion of phosphate by kidneys

FGF23 inhibits the PTH-release. 1-alfa-hydroxylase is now inhibited leading to less active vitamin D. this results in less phophate intake of the intestine. It inhibits 1 a hydroxylase and PTH = lower uptake by the intestine and it stimulates the phosphate excretion resulting in a decrease of serum phosphates

What could cause hypercalciemia if PTH is low

PTH should be low (aka normal reaction to high calcium). The problem is therefore not related to the parathyroid glands

• multiple myeloom

• bone metastasis

• PTHrp procusing hormones

• sarcoidose

• tuberculosis

• thiazide diuretics

• increased vitamine D levels (mostly due to increased intake)

What could cause hypercalciemia with high PTH?

• primary hyperparathyroidism

• tertiary hyperparathyroidism

How do you measure calcium in the lab

colorimetric analysis, by shining light at a mix of serum and reagens.

How do you measure PTH in the lab

immunometric assay, the sandwich assay/methode.

How do you measure 25-(OH)-vitamin D

competitive immunoassay or LC-MS/MS (chromotography)

How do you measure 1,25(OH)vitamin D

LC-MS/MS (chromotography)

What are indications for measuring active vitamin D

• granulomatous disease/ sarcoidosis

• lymphoproliferate disease

• 1-alfa-hydroxylase deficiency

• vitamin D resistance

How do we measure bone markers in the lab?

CTX and P1NP can be measured using immunometric assays

What could interfere in immunometric assays?

• heterophilic antibodies —> falsely increased or decreased

• macromolecules —> falsely increase

• medication

Please describe the term “sex”

fysical aspects of biological sex, bases on characteristisch such as chromosoms and anatomy

Please describe the term “gender”

the psychosocial aspect or the subjective feeling to belong to none,one, more than one or other genders. Gender is can be seen as a social construct

What is the definition of cisgender?

alignment of birth assigned sex and gender identity

What is the definition of transgender?

incongruence of sex assigned at birth and gender identity.

In the ICD-11 classification, what are the limitations of the diagnosis?

• diagnosis not possible before the onset of puberty

• gender variant behaviour and preferences are not a basis for assigning diagnosis

Which term is used in the ICD-11 classification?

gender incongruence

Which term is used in the DSM-5 guidelines?

gender dysphoria

What are the criteria for the DSM-5 diagnosis of gender dysphoria?

a. two or more of the following criteria for > 6 months

• a significant incongruence

• a strong disire to be rid of ones sexual characteristics due to the incongruence

• a strong disire for characteristischs of a gender other than the one assigned at birth

• a disire to be of another gender

• a disire to be treated as the other gender

• a strong convition that one has typical reactions and feelings of a gender other than once assigned at birth

b. the condition must be associated with clinically significant distress or impairment

What has changed in the DSM-5 criteria over the last few years

• gender identity disorder —> gender dysphoria

• moved away from the chapter about paraphilias and sexual disorders

• letting go of the binairy construct

• stricter criteria for diagnosis in children

What is the purpose of the diagnostic phase in transgender healthcare?

gather information

• nature and degree of gender dysphoria

• exploring treatment wishes and expectations

• mapping once capacity and coping strategies

• giving advice on medical and/or psychological treatment

fully inform someone about the treatment process

What is the difference between gender dysphoria and gender incongruence?

distress is a neccerary part of the gender dysphoria diagnosis. In gender incongruence this is not.

name 3 factors which influence gender identity

• biological factors

• psychosocial factors

• social factors

Explain the sexual differentation theory

Gender dysphoria develops prenatal because genital development happens in the first trimester and brain development in the second and third trimester.

What is the mosaic theory?

The brain has more female parts and more male parts. Each brain is a mosiac of these parts which are denser than others.

What is the body perception theory?

Body perception is different in transgender people and cisgender people. It is unclear if this is a consequence of gender incongruence or a cause of gender incongruence.

What are the 5 base densities in x-ray imaging?

• air

• fat

• soft tissue

• bone

• metal

air had a low opaque and is black

metal/ bone has a high opaque and is white

Which methode can be used to determine bone age in pediatric patients?

CRITOE

different ossification centers ossify at different ages

1 years old = capitellum

3 years old = radial head

5 years old = internal epichondyl

7 years old = trochlea

9 years old = olecranon

11 years old = external epichondyl

What can you do to check if pediatric imaging is abnormal?

compare with the other side

What can you say about the age and bone density in this image?

This bone is near peak bone densitiy age, meaning around 30 years old

What can you say about the age and bone density in this image?

The contrast between the cortex and central bone is higher. This bone is less dense. It probebly belongs to someone with osteopenia or osteoporosis. Age is estimated around 85 years old.

What type of fracture is this?

transverse fracture

What type of fracture is this?

linear fracture

What type of fracture is this?

olbique fracture, non displaced

What type of fracture is this?

oblique fracture, displaced

What type of fracture is this?

spiral fracture

What type of fracture is this?

greenstick fracture

What type of fracture is this?

comminuted fracture

How many views are needed to review traumatic injury?

at least 2 view

What do we see on this image?

torus / buckle fracture, an imcomplete fracture of a long bone characterized by bulging of the cortex. This can be the consequence of axial force on the bone mostely seen in children.

What are different stages of bone healing?

1. hematoma

2. inflammation

3. fibrovascular

4. bone formation

5. remodeling

What is the SALTER- HARRIS classification?

a classification for fractures involving the growth plate in children.

S = separated growth plate

A = above the growth plate —> in the metaphysis

L = beLow the growth plate —> in the epiphysis

T = through the growth plate —> metaphysis + epiphysis + epiphysial plate (growth plate)

ER = erasure / compression of the growth plate

What is a stress fracture?

a fracture as a result of abnormal pressure on a normal bone. Often seen after no or minimal trauma in periods with increased physical activity. 95% of stress fractures are fractures of the lower limb. In röntgen it can be seen as vage dots on the imaging

—> grey cortex sign

what is an insufficiency fracture?

a fracture as a result of normal stress on a abnormal bone. A pathological fracture is a type of insufficiency fracture usually reserved for a focal bone abnormality e.g. malignancy

What is an atypical femoral fracture?

a fracture of the femoral bone, distal of the lesser trochantor but proximal to the supracondylar flaire. It is associated with the long term use of biphosphantes.

What are the major criteria for atypical femoral fracture?

4 out of 5 criteria needed:

• no/minimal trauma

• mainly transvers; medial may be oblique

• must involve the lateral cortex

• no or minimal comminution

• endosteal or periosteal thickening

What are exclusion criteria for the atypical femoral fracture?

• tumors are found

• spiral fracture

• comminuted fracture

• femoral neck

• periprostetic

What are possible indications for a bone biopsy?

• possible osteomalacie

• research

• osteoporosis in young people

• metabolic bone disease

• renal osteodystrophia

At what location in a bone biopsy taken?

transiliacaal

Of what is cortical bone composed?

Haverse systems

Explain the colors of the Goldner trichrome

blue / green = mineralized bone

red lining = osteoid

red/pink dots near red lining = osteoblast

red / pink dots near mineralized bone creating holes = osteoclast

red cell captured in bone = osteocyt

How can osteomalacie be diagnosed?

DEXA and biopsy with tetracycline staining

What do we see in the following image?

we see increased osteoid, with few osteoblast.

—> osteomalacie

What do we see in the following image?

osteomalacie

What do we see in the following image?

A low trabecular bone volume, few/ thin trabecels

—> osteoporosis

What do we see in the following image?

A low trabecular bone volume, few/ thin trabecels

—> osteoporosis

What do we see in the following image?

A tetracycline imaging in which we see disturbed bone mineralization = osteomalacie

What do we see in the following image?

normal bone biopsy

What do we see in the following image?

osteosclerosis

What do we see in the following image?

osteoslerosis

What does tetracycline labeling stain? 

Border between osteoid and mineralized bone / mineralization front

after how long can you state there has been a non-union fracture?

6 - 9 months

What are risk factors for the non union of a fracture?

• high age

• poor nutrition status

• nicotine/ alcohol consumption

• hyperparathyrodism

• bone loss at the fracture

• loss of blood supply

• infection

• insuffiecient immobilization

• soft tissue interposition

What can you do to motivate your patient?

• shared decission making

• applicable and divers advice

• advice by mouth, digital and on paper

• refferal to specialist (dietician, physiotherapist e.g.)

• stimulate to think about what is important for the patient

When is the instrinsic pathway activated?

endothelial damage

When is the extrinsic pathway activated?

external trauma to the vessel

How do we categorise DVT?

provoked and unprovoked

What do we classify as provoked DVT?

• recent trauma / surgery

• immobilization

• use of estrogens

• pregnancy / post partum

• active malignancy

• traveling for longer than 8 hours

What do we classify as unprovoked DVT?

• traveling for less than 8 hours

• trombophilia

• trombophlebitis

• history of VTE

• obesity

• elders

• chronic (inflammatory) disease

• smoking

what is the recurrence rate of an provoked DVT

if it was surgery: 3% within 5 years

other reason: 15% within 5 years

what is the recurrence rate of an unprovoked DVT

30% within 5 years

How do you recognize vitamin K antagonist?

coumarines:

• acenocoumarol

• fenprocoumon

What is the working mechanism of vitamin K antagonist?

inhibiting vitamin k dependent production of factors 9,10,7,2. The effect is not immediately since the already produced factors are still in place.

What are interactions vitamin K antagonist have?

• other anti coagulants

• NSAIDs

• vitamin K containing diet

• co-trimoxazol and miconazol

  —> inhibit CYP —> inhibits breakdown of vitamin K antagonist —> higher levels —> higher bleeding risk

What can you do to reserve the effect of vitamin K antagonist?

• tourniqet / surgery

• whole blood or plasma transfusion

• vitamin K (effect after 12-24 hours)

• four factor concentrate

How do you recognize DOACs

• dabigatran

• rivaroxaban

• apixaban

• edoxaban

tran = factor 2

xaban = factor X (10)

What is the working mechanism of DOACs

Direct inhibition of factor 2 or factor 10.

How long do DOACs work?

depending on renal function + 24 hours

How long do vitamin K antagonist work?

acenocoumarol = 3-5 days

fenprocoumon = + 3 weeks

What are interactions DOACs have

• other anticoagulants

• NSAIDs due to the increased risk of GI-bleeds

• contra-indication = renal function (<15 ml/min no DOAC can be given)