Seen PBL2 Flashcards
what does myalgia mean? [1]
what is Polymyalgia rheumatica (PMR)? [1]
which population is PMR typical of? [1]
myalgia means pain within the muscles
Polymyalgia rheumatica (PMR) is a common systemic inflammatory disease that is one of the most common indications for long-term steroids. It is characterised by myalgia and muscles stiffness with preponderance to the neck, shoulder and pelvic girdle.
PMR is predominantly a disease of older adults and rarely presents before 50 years old
what are two factors linked to PMR? [2]
Both genetic and environmental factors have been linked with the aetiology of PMR:
Genetic: PMR, like GCA, has been associated with several human leucocyte antigen (HLA) alleles (e.g. HLA-DR4).
Environmental: the cyclical pattern of _cases and peak incidence in winter month_s suggests an infectious trigger.
what is the pathophysiology of PMR?
The name PMR implies a myopathic process, however, the muscle in PMR is normal on histopathological assessment. The predominant site of inflammation includes bursae and tendons. Bursae are fluid-filled sacs that counteract the friction associated with tendons. Despite the site of inflammation, patients still present with generalised muscle stiffness and pain, particularly in the shoulder and pelvic girdles.
There are characteristic sites in the upper and lower extremities associated with PMR:
Shoulder girdle: subdeltoid/subacromial bursitis and biceps tenosynovitis.
Pelvic girdle: bursae around the greater trochanters and ischial processes. liopectineal and iliopsoas bursitis. Hamstring tendinitis and hip synovitis.
what is fibromyalgia?
Fibromyalgia is a chronic pain syndrome diagnosed by the presence of widespread body pain.
The 1990 American College of Rheumatology criteria for the classification of fibromyalgia required that an individual had widespread pain (front and back, right and left, both sides of the diaphragm) for at least 3 months in addition to tenderness (digital palpation at an approximate force of 4 kg) of at least 11 out of 18 designated tender point sites.[1]
fibromyalgia pathophysiology?
theorized to be a malfunctioning of the central nervous system (CNS), characterized by central sensitization, which is a heightened pain perception accompanied by ineffective pain inhibition and/or modulation.
This increased response to peripheral stimuli causes hyperalgesia, allodynia, and referred pain across multiple spinal segments, resulting in chronic widespread pain and decreased tolerance to sensory input of the musculoskeletal system.
what is BMI?
what are BMI ranges?
what is the unit?
BMI (body mass index) is a measure of whether you’re a healthy weight for your height.
BMI weight ranges
- *Less than 18.5 =** Underweight
- *Between 18.5 - 24.9 =** Healthy Weight
- *Between 25 - 29.9 =** Overweight
- *Over 30 =** Obese
unit: kg/m2
which populations is BMI not reliable for? [4]
Pregnant women [1]
If you are very muscular [1] (assumes average body weight is fat not muscle)
If you are of Asian origin [1]
Older people (over 65, possibly over 60) [1]
alternative tests for BMI? [2]
Waist circumference [1]
Waist to hip ratio [1]
Waist to height ratio [1]
whats the difference between causes of type 1 and 2 diabetes?
Type 1 diabetes mellitus (T1DM)
Autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system. This results in an absolute deficiency of insulin resulting in raised glucose levels
Patients tend to develop T1DM in childhood/early adult life and typically present unwell, possibly in diabetic ketoacidosis
Type 2 diabetes mellitus (T2DM)
This is the most common cause of diabetes in the developed world. It is caused by a relative deficiency of insulin due to an excess of adipose tissue. In simple terms there isn’t enough insulin to ‘go around’ all the excess fatty tissue, leading to blood glucose creeping up.
what is difference in treatment for type 1 and 2 diabetes?
Type 1 diabetes
patients always require insulin to control the blood sugar levels. This is because there is an absolute deficiency of insulin with no pancreatic tissue left to stimulate with drugs
different types of insulin are available according to their duration of action
Type 2 diabetes
Lots of people with Type 2 diabetes don’t take any medication, and they instead treat their diabetes by eating well and moving more, our latest research DiRECT has even shown that weight loss can put Type 2 diabetes into remission.
the majority of patients with type 2 diabetes are controlled using oral medication
the first-line drug for the vast majority of patients is metformin (Increases insulin sensitivity
Decreases hepatic gluconeogenesis)
second-line drugs include sulfonylureas, gliptins and pioglitazone. Please see the table below for further information
if oral medication is not controlling the blood glucose to a sufficient degree then insulin is used
how do you diagnose diabetes?
- if patient is symptomatic
- if patient is asymptomatic
If the patient is symptomatic:
- fasting glucose greater than or equal to 7.0 mmol/l
- random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.
what happens in perimenopause –> menopause with regards to hormones?
what symptoms occur because of this?
ovaries have far fewer functional follicles: menstrual cycles are anvolatory (dont ovulate, bc none of the follicles are responsive enough to FSH and LH to cause ovulation). also have fewer ovarall follicles. this resutls in less oestrogen and progesterone produced, which means get more GnRH causing LH and FSH.
The process of the menopause begins with a decline in the development of the ovarian follicles. Without the growth of follicles, there is reduced production of oestrogen. Oestrogen has a negative feedback effect on the pituitary gland, suppressing the quantity of LH and FSH produced. As the level of oestrogen falls in the perimenopausal period, there is an absence of negative feedback on the pituitary gland, and increasing levels of LH and FSH.
The failing follicular development means ovulation does not occur (anovulation), resulting in irregular menstrual cycles. Without oestrogen, the endometrium does not develop, leading to a lack of menstruation (amenorrhoea). Lower levels of oestrogen also cause the perimenopausal symptoms.
BUT: this is all really erratic c.f. reproductive period. both this erraticness and decreasing oestrogen levels cause
- night sweats & trouble sleeping
- vaginal dryness -> dysparenuia (pain during sex)
- oestrogen sustains bone density -> without it can lead to osteoporosis & CVS diseases
what should women entering menopause be checked for? [2] why? [1]
low levels of oestrogen can cause
- increased LDL cholesterol levels
- osteoporisis -> A bone density scan uses low dose X-rays to see how dense (or strong) your bones are. You may also hear it called a DEXA scan.
what scores do u get from a dexa scan? [2]
what would signal osteoprosis? [1]
what scores do u get from a dexa scan? [2]
- *The T-score** is a comparison of a person’s bone density with that of a healthy 30-year-old of the same sex.
- *The Z-score** is a comparison of a person’s bone density with that of an average person of the same age and sex.
what would signal osteoprosis? [1]
T score: ≤-2.5. = osteoporosis
what can give to people to decrease risk of osteoporisis? [2]
what can you can give as treatment? [1]
what can give to people to decrease risk of osteoporisis? [2]
Ca2+
Vit D
what can you can give as treatment? [1]
bisphosphinates
what is Osteoporosis ?
Osteoporosis is a condition where there is a reduction in the density of the bones.
what is creatinine?
how do you know if you have problem with kidneys?
- Byproduct of muscle metabolism
- Used as a key measure of renal function as it is excreted unchanged by the kidney: Normally, your kidneys filter creatinine from your blood and send it out of the body in your urine. If there is a problem with your kidneys, creatinine can build up in the blood and less will be released in urine
what are ranges for stage 1, 2 & 3 hypertension?
Stage 1 hypertension - BP in surgery/clinic is ≥140/90 mm Hg and ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) ranges from 135/85 mm Hg to 149/94 mm Hg.
Stage 2 hypertension - BP in surgery/clinic is ≥160/100 mm Hg but less than 180/120 mm Hg and ABPM or HBPM is ≥150/95 mm Hg.
Stage 3 or severe hypertension - systolic BP in surgery/clinic is 180 mm Hg or higher or diastolic BP is 120 mm Hg or higher.
risk factors for type two diabetes?
describe the different phases of insulin release due to glucose stimulation xo (2)
1st phase: immediate release due to increased blood glucose levels
2nd phase: sustained, slow release of newly formed insulin for storage vesciles
explain the main mechanism of insulin action to allow glucose into the cell !
when not enough insulin:
- IRS (adaptor protein) & PI3K (lipase kinase) & Akt (protein kinase) are all in the cytoplasm and inactive. causes:
- GLUT4 transporters are stored intracellularly. (cant get glucose across (or LOTS of glucose across)
- glucose cant cross membrane
when enough insulin:
- insulin binds to tyrosine-kinase receptor: causes autophosporylation of tyrosine-kinase receptor:
- IRS can bind to the phosphorylated receptor: causes IRS to be phosphorylated
- when IRS is phosphorylated, PI3K binds to IRS-P and PI3K becomes phosphorylated.
- phosphorylated PI3K causes change in membrane lipid: PIP2 –> PIP3
- PIP3 causes activation of Akt
- Akt causes change of GLUT4, to be inserted into membrane = les glucose through !
what do osteoclasts look like? [1]
explain mechanism of bone remodelling occurs xox
osteoclasts - multinucleated macrophage relation
- look for areas of bone that need to be renewed
- make leak proof seal over the area
- secrete enzymes & HCl that will dissolve the calcium hydroxyapatite
- osteoclasts take up calcium & proteins pump into interstitial fluid
- osteoclasts find new area
- osteoblasts come in & fill lacuna with osteoid - firstly NOT MINERALISED
- *-** approx 7-10 days osteoid is mineralised
- osteoblast becomes encased & beomes osteocyte
what substance is secreted that makes osteoclasts differentiate into osteoclasts? [1]
what substance is secreted that makes osteoclasts differentiate into osteoclasts? [1]
RANKL
how does PTH cause Ca2+ reabsorbtion from bones via the increase of activity and no. osteoclasts? [3]
Ca2+ reabsorbtion from bones - increases activity and no. osteoclasts
PTH binds to osteoblasts
osteoblasts produce RANKL
osteoclasts have RANKL receptor
activates osteoclasts
explain how intramembranous ossificatin occurs xo
- ossification centre appears in fibrous connective tissue membrane: here mesenchymal cells condense and differentiate as osteogenic cells: osteoblasts
- Osteoblasts secrete bone matrix (osteoid) & matrix becomes calcified with calcium hydroxyapatite
- trapped osteoblasts become osteocytes
- Mesenchyme on outside condenses: **periosteum
-**
blood vessels growing to supply the bone with nutrients will bring in osteoclasts, which can then remodel the bone into compact/cortical bone on the outside and trabecular bone on the inside.
Explain how primary endochondral ossification occurs xo
_Endochondral ossification: t_wo step process: produces cartilage and then changes this cartilage to bone
- Mesenchymal cells condense and differentiates into chondroblasts to produce hyaline cartilage model extracellular matrix (so they use collagen type 2 rather than collagen type 1).
- the perichondrium forms around cartilage model and holds all the mesenchymal cells next to the condensing bone
- To begin with, ECM make more collagen type 2, more proteoglycans: causes cartilage to grow in legnth and width (into the shape of the bone): causes to be further away from nutrient source
- chondrocytes now in the middle will begin to deteriorate as there is no blood supply into this cartilage
- this creates cavities, right in the centre, where the cartilage used to be. When they die, this triggers calcification as it triggers a Ph change: It releases vesicles in the chondrocytes with enzyme like alkaline phosphatase which changes the ph and encourages calcification of the matrix.
At this time, a blood vessel known as the nutrient artery can penetrate the perichondrium and begin to bring in osteoclasts from the haemopoietic cells to start remodelling: break down some of the spongy bone to create a marrow, or medullary, cavity in the centre.
Bone on the inside and bone on the outside grow towards each other to completely replace the cartilage.
how does appositional growth of bone occur? (to the side)
- osteoprogenitors in periosteum differentiate as osteoblasts – secrete new bone matrix to form compact, cortical bone (osteons) and grow on either side of a blood vessel.
- these ridges get bigger and eventually form a tunnel with a blood vessel right in the centre.
- Inside tunnel: Former periosteum becomes endosteum due to being enclosed inside the bone due to bone growth. It still has progenitor cells
- Osteoblasts make new bone lamellae filling tunnel
