L&B + CV&R - Non-Anatomy Lectures Flashcards
1
Q
What are the 2 types of bone ?
A
Cortical (compact) and trabecular (spongy)
2
Q
What type of bone makes up diaphyses (shafts) ?
A
Cortical
3
Q
What type of bone makes up epiphyses (ends of bone) and vertebral bodies ?
A
Trabecular
4
Q
Which bone type is more susceptible to conditions associated with increased bone turnover ?
A
Trabecular
5
Q
What percentage of the human skeleton is comprised of trabecular bone ?
A
20%
6
Q
What percentage of bone is inorganic ?
A
70%
7
Q
What percentage of bone is organic ?
A
22%
8
Q
What percentage of bone is water ?
A
5-8%
9
Q
What is inorganic bone comprised of ?
A
95% calcium hydroxyapatite (the rest is impurities)
10
Q
What is organic bone composed of ?
A
85% collagen type 1, 15% other collagens, proteins, glycoproteins and cells
11
Q
What are the 3 types of bone cell ?
A
Osteoblasts
Osteoclasts
Osteocytes
(+ osteogenic)
12
Q
What is the function of osteoblasts ?
A
Bone formation, regulation of bone turnover
13
Q
What is the function of osteocytes ?
A
Sense mechanical strain and release signals (prostaglandins, nitric oxide) that modulate the function of neighbouring cells
14
Q
Where are osteocytes found ?
A
Embedded in the bone matrix, each within their own lacuna
15
Q
What is the function of osteoclasts ?
A
Bone removal (resorption)
16
Q
What are osteoblasts and osteocytes derived from ?
A
mesenchymal stem cell precursor
17
Q
What are osteoclasts derived from ?
A
hemopoietic mononuclear cells
18
Q
What are the 4 stages of the bone remodelling cycle ?
A
Quiescence
Resorption
Reversal
Formation
19
Q
What are osteoclasts rich in ?
A
Enzyme TRAP
20
Q
What does the RANK-RANKL interaction do ?
A
Responsible for osteoclasts maturation, Stimulates bone resorptive activity of mature osteoclasts
21
Q
What does osetoprotegerin (OPG) do ?
A
It bins to RANKL and prevents RANK activation, inhibiting osteoclasts formation
22
Q
What do osteoclasts secrete ?
A
Hydrochloride acid and proteolytic enzymes
23
Q
What can mesenchymal stem cells differentiate into ?
A
Osteoblasts, myocytes and chondrocytes
24
Q
What molecule causes osteoblasts differentiation ?
A
Cbfa1
25
What do osteoblasts secrete ?
Cytokines/GF, enzymes and proteins
26
What are the 2 eventual forms of osteoblasts ?
Osteocytes or lining cells
27
What secretes RANKL?
Osteoblasts
28
What do osteoblasts secrete that creates new bone ?
Osteoid
29
What stimulates bone remodelling ?
IL-1,tumour necrosis factor, PTH, Vit D
30
What inhibits bone remodelling ?
Oestrogens, androgens and calcitonin
31
What changes to the spine occur during adolescence ?
Increase in size and trabecular thickness
32
What changes to the long bones occur during adolescence?
Increased length and diameter
33
What age is peak bone mass obtained ?
~30 yrs
34
What happens to bone mass post-menopause?
Accelerated bone loss
35
What do oestrogens and androgens do to bone ?
Oestrogen = bone maturation and mineralisation
Androgen = proliferate chondrocytes
36
Define osteoporosis
A decrease in bone mass causing compromised bone strength and an increased risk of fracture
37
What happens to trabecular bone in osteoporosis?
The trabecular thins and it’s continuity is disrupted
38
What causes post-menopausal osteoporosis (PMO)?
decided oestrogen levels, resulting in an excess of RANK-L
39
What percentage of BMD variability is caused by genetic factors ?
60-80%
40
What is Colles fracture ?
Falling onto outstretched hand , radius fractures and displaces dorsally
41
At what age does the risk of hip fractures massively increase ?
70 yrs
42
Name 3 risk factors for osteoporotic fractures
Older than 65, family history, malabsorption syndrome
43
Outline percentages detailing the complications of osteoporotic fractures
30% permanent disabled, 50% can’t return to full independence, 12-20% die within 1 year
44
What scanning method is used in the diagnosis of osteoporosis ?
DXA Scan
45
What are the T-score ranges for diagnosis ?
Greater or equal to -1 = normal
-1 to -2.5 = osteopenia
Less than -2.5 = osteoporosis
More than -2.5 + prescience of 1 or more fractures = established osteoporosis
46
What is the aim in managing osteoporosis?
Reducing Fx risk
47
What is absolute fracture risk ?
Age + past history + BMD
48
What is the calcium intake recommended for post-menopausal women ?
1000-1500 mg/day (vit D = 800 IU/day)
49
Name 3 drugs used as osteoporosis treatments ?
Bisphosphonates, SERMS (Raloxifene), Estradiol (semisynthetic oestrogen)
50
What does DENOSUMAB do ?
It targets RANK-L and inhibits bone resorption, it is a monoclonal antibody
51
What does ROMOSUMAB do ?
It’s inhibits sclerostin, increasing bone formation and decreasing bone resorption
52
How much does osteoporosis treatment reduce fracture risk by ?
Half
53
How man kg of Ca are there in the body ?
1
54
What percentage of serum calcium is free ?
47%
55
What is the adjusted calcium equation ?
Ca (adj) = Ca(tot) + [0.02[45-alb)]
56
What is a normal Ca (adj) value ?
2.2-2.6 mmol/L
57
What are the main organs involved in Ca homeostasis ?
Kidney , gut, bone , parathyroid glands
58
What are the main hormones involves with metabolic control of calcium ?
PTH, vit D (active 1.25DHCC form)
59
What’s are the WHOs 6 Domains of QOL ?
Physical, environment, social relationships, psychological, level of dependence, spiritual
60
Name the 3 common musculoskeletal ageing syndromes
Joints = osteoarthritis
Bone = osteoporosis
Muscles = Sarcopenia
61
What makes healing of articulation cartilage slow ?
No innervation, vascularisation or macrophages
62
What cells are in articulate cartilage ?
Chondrocytes
63
What percentage of chondrocytes are lost between 40-80 years old ?
50%
64
What maintains swelling pressure of proteoglycans ?
ECM contains hydrophilic proteoglycans
65
Define osteoarthritis
A disorder of synovial joints which occurs when damage triggers repair processes leading to structural damage within a joint
66
Name 3 features of osteoarthritis
Localised loss of cartilage
Osteophyte formation
Mild synovitis
67
How long does morning stiffness last for osteoarthritis?
Wither no morning stiffness or less than 30 minutes
68
What growth hormone is responsible for differentiating osteoblasts ?
IGF-1
69
What is the rate of rapid bone loss in the first 5 years after menopause ?
2-3%
70
What are the most common fragility fractures ?
Spine , hip and wrist
71
Outline the SARC-F screening tool for sarcopenia
Strength
Assistance walking
Rise from chair
Climb stairs
Falls
72
What is subluxation?
Dislocation if a joint where contact to some of the articulating surfaces remains
73
What is grade 1 ligament injury ?
Fibres stretched but normal range on stressing
74
What is grade 2 ligament injury ?
More fibres involved, laxity on stressing but definite end point
75
What is grade 3 ligament injury ?
Complete tear, excessive laxity and no end point. May be pain free as nerve fibres torn
76
Outline management of grade 1 and 2 ligament injury
Promote tissue healing, prevent joint stiffness, protect against further damage, strengthen muscles
77
Outline management of grade 3 ligament injury ?
Protective bracing or surgical repair/ reconstruction
78
What e muscles are most commonly affected by strains and tears ?
Hamstrings, quadriceps femora’s and gastrocnemius
79
What tendon is most likely to rupture ?
The quadriceps tendon
80
What is the treatment for hamstrings rupture ?
NSAIDs, electrotherapy, strength and stretching (physio), surgery ??
81
What happens in muscles contusion ?
Local damage and bleeding, due to direct blow
82
What is myositis ossificans ?
Ossification due to severe contritions, haematoma calcification
83
What are the 2 most common tendon injury sites ?
Achilles tendon and supraspinatus
84
What are the 2 common nerves injured in sport ?
Ulnar nerve at elbow, common fibular/personal nerve at the neck of the fibula
85
Outline tendon composition
20% = cellular-tenocytes
70% = water
30% solids = collagen 1, ground substance, elastin, other collagen (collagen 3)
86
What is tendinopathy ?
Painful conditions that arise in and around tendons, in response to overuse
87
What are the 3 phases of tendon healing ?
Inflammation (day 0-7), repair (day 3-60), organisation and remodelling (day 28-180)
88
What is the function of a tendon ?
To transmit force
89
What happens in the inflammation step of tendon healing ? (Day 0-7)
Inflammatory cells migrate
Defect filled with granulation tissue, haematoma and tissue debris
Matrix proteins laid down as scaffolding for collagen synthesis
90
What happens during the repair step of tendon healing? (Day 3-60)
By day 5 = fibroblast/tenocyte migrate and begin to synthesise collagen 3 (laid in random orientation)
During 4th week = fibroblasts proliferate synthesising and reabsorbing collagen, collagen switched to type 1, vascular ingrowth via fibronectin scaffolding
91
What happens during the remodelling phase of tendon healing ? (Day 28-180)
Cross linking between fibrils increases tendon tensile strength, final stability reached
92
What is the composition of ECM ?
50% water, proteins, glycoproteins, proteoglycans, glucosaminoglycans, collagen
93
Where is type 1 collagen found ?
Skin, bone, tendons, ligaments, cornea, internal organs
94
Where is type 2 collagen found ?
Cartilage, IVD, notochord
95
Where is type 3 collagen found ?
Skin, blood vessels, internal organs
96
Where is type 4 collagen found ?
Basal lamina
97
What is collagen structure described as ?
Triple helix , 3 polypeptide chains
98
What is osteogenesis imperfecta ?
Brittle bone disease, collagen type 1
99
What are the 5 derivatives of the mesoderm ?
Notochord, paraxial mesoderm, intermediate mesoderm, lateral plate mesoderm, extraembryonic mesoderm
100
What mesoderm forms somites ?
Paraxial mesoderm
101
What does the intermediate mesoderm form ?
Genitourinary system
102
What does the lateral plate mesoderm form ?
The parietal and visceral layers of mesoderm
103
What muscles aren’t formed by the mesoderm ?
Pupil, mammary and sweat gland smooth muscles, there’s are from the ectoderm
104
What can you use somite numbers for ?
To determine the age of an embryo
105
What regulates somitogenesis?
Clock and wave mechanism - FGF family, Wnt, Notch act as alarms (clocks)
106
How many somite pairs are present by the end of week 5 development ?
42-44 pairs, these go on to form the axial skeleton
107
What is a somite?
Paired blocks of mesoderm cells that are located on either side of the neural tube. They give rise to the axial skeleton
108
What do sometimes differentiate into ?
Sclerotome and dermomyotome
109
What does the sclerotome turn into ?
Ribs and vertebrae
110
What does the dermomyotome split into ?
The dermatome and the myotome
111
What does the dermatome turn into ?
Dermis and CT
112
What does the myotome turn into ?
Muscle
113
What are myoblasts ?
Myocyte precursors
114
What controls myoblast cell division ?
The presence of growth factors
115
What happens to myoblasts when growth factors are depleted ?
They stop dividing
Fibronectin secreted onto ECM, binding via integrins
Myoblasts align into chains and fuse, cell membranes disappear, multi-nucleated primary myotubes
116
What mediates myoblasts differentiation ?
Myogenin
117
In the neural tube, what does Wnt and BMP do ?
Activate MYOD in the dermomyotome, creates a group of muscle cell precursors which express MYF5
118
In the notochord, what do SHH and Noggin induce?
Sclerotome formation
119
In the lateral plate mesoderm, what do Wnt and BMP do ?
Activate MYOD/MYF5
120
What do MYOD/MYF5 do ?
Activate muscle specific genes
121
What happens if both MYF5 and MYOD1 are present ?
This is a loss of function mutation, causes complete lack of skeletal muscle formation
122
What genes control differentiation in the 3 muscle types (smooth,skeletal and cardiac) ?
Skeletal = MYOD, MYF5, Myogenin
Smooth = Serum Response Factor (SRF)
Cardiac = MYOD NOT involved
123
What type of mesoderm do the 3 types of muscle develop from ?
Skeletal = paraxial mesoderm
Smooth = splanchnic mesoderm
Cardiac = splanchnic mesoderm
124
Below what age is scaphoid fracture unlikely to occur (and why) ?
10 years old, the scaphoid is mostly cartilage up until this point
125
What is Torus fracture ?
Caused by falling onto hand, bone bends but doesn’t break through (buckles)
126
What is a green stick fracture ?
Bone is only fracture on one side, fracture isn’t the full way through the bone
127
What is a plastic bowing fracture ?
Only occurs in long bones, bone bends but doesn’t snap in any location
128
What is the Salter-Harris classification ?
A method used to grade fractures that occur in children involving the epiphyseal growth plate
129
What are the classifications of Salter-Harris (salter mnemonic) ?
Separated growth plate = I
Above the growth plate = II
Lower than the growth plate = III
Through the growth plate = IV
ERasure of growth plate (crush) = V
130
What type of fracture in infants is classed as non-accidental injury ?
Bucket handle fracture , causes injury to the metaphysis
131
What is Rickets ?
Softening of the bones due to deficiency or impaired metabolism of Vitamin D. Causes leg bowing and other skeletal problems.
132
What is the Trendelenburg test ?
Detects weakness of gluteus medius and minimus, standing on each leg in turn. If hip affected, pelvis will tilt by dropping at the opposite side and the body leans away from affected side.
133
What are menisci ?
C-shaped wedges of fibrocartillage, there is a medial and lateral menisci. They improve the fit of the knee joint and act as shock absorbers
134
Which of the collateral ligaments is NOT attached to the joint capsule ?
FCL (fibular collateral ligament)
135
What is the TCL (tibial collateral ligament) attached to ?
The joint capsule and medial meniscus
136
What is the angle between the femur and tibia called ?
The Q angle (approx 15 degrees)
137
What is Genu Varum?
Bow leg, angle between longitudinal axis of bones is <17 degrees
138
What is Genu Valgum?
Knock knee, angle between longitudinal axis of bones >17 degrees
139
What is the crown to rump length at 24 weeks ?
200 mm
140
What are the 6 zones present in developing bones ?
Resting cartilage
Proliferation of chondrocytes
Maturation (no more mitosis)
Hypertrophy (vacuole formation)
Cartilage Degeneration
Osteogenic activity
141
What is the definition of differentiation ?
Changing one cell type to another
142
What regulates cell differentiation?
Transcription factors
143
What can differentiation affect ?
Cell : Shape, size, membrane potential, metabolic activity and responsiveness to signals
144
When do limb buds become visible ?
By the end of week 4
145
When does limb morphogenesis take place ?
Week 4-8
146
Which limbs develop slowest ?
Lower limb, but they catch up
147
What is the 1st sign of limb musculature ?
Mesenchyme near the limb buds
148
What is mesenchyme compromised of ?
A matrix of Collagen fibres
Hyaluronic acid
Glycoproteins
149
Are there nerves in the early limb bud?
No
150
What does the limb bud consist of ?
Mesenchymal core with a covering cubital ectoderm layer
151
What does ectoderm thickening at the distal border form ?
Apical Ectodermal Ridge (AER)
152
What do AER cells differentiate into ?
Cartilage and muscle
153
What is limb outgrowth initiated by ?
Secretion of FGF10
154
What does the dorsal ectoderm express?
Radical fringe
155
What does the ventral ectoderm express ?
Engrailed-1
156
Once the AER is established what does it express and why ?
FGF4 and FGF8, to maintain the undifferentiated zone at the distal end
157
Which transcription factor designates the upper limb ?
TBX-5
158
Which transcription factor designates the lower limb ?
TBX-4
159
What happens at 6 weeks in limb development ?
Terminal portion of the buds flatten to form hand and foot plates
160
What separates the segments of the developing limb ?
Constriction
161
What are the 3 components of the developing limb ?
Stylopod = humerus + femur
Zeugopod = radius/ulna + tibia/fibula
Autopod = carpals/metacarpals/digits + tarsals/metatarsals/digits
162
What are HOX genes ?
Genes that regulate the positioning of the body structures
163
What HOX genes position the limbs ?
9-13
164
What is polydactyly ?
Extra digits cause by mesoderm defect due to mutation of HOX genes, SHH or Wnt
165
What causes the AER to separate into 5 digits?
Cell death in the AER
166
What day in development is digit separation complete ?
Day 56
167
What happens during week 7 of limb development ?
The upper and lower limbs rotate in opposite directions, occurring from coronal to parasagittal plane then along the axis
168
Which direction and angle do limbs rotate by ?
Upper = 90* laterally
Lower = 90* medially
169
What drives mesenchyme condensation and differentiation into chondrocytes ?
BMP expression
170
What is cell proliferation, increased density, differentiation and cell death induced by in joint formation ?
WNT 14
171
By what week are primary centres of ossification present in all long bones ?
Week 12
172
What does calcified cartilage matrix not allow?
Diffusion of nutrients
173
What does the lack of nutrients cause in calcified cartilage matrix ?
Cells to die, leaving spicules which act as scaffolding on which bone can be deposited
174
What happens when blood vessel grow into the bones periosteum ?
It brings progenitor cells
175
What happens to progenitor cells in periosteum ?
They form osteoblasts, osteoclasts and osteocytes
176
What does intramembranous bone growth do ?
Increases bone width (diameter) by replacing bone in the medullary cavity
177
What does endochondral bone growth do ?
Increases bone length, cartilage is ossified at the epiphyseal growth plates
178
What is Achondroplasia?
A disorder of bone girth affecting endochondral ossification in the long bones of arms and legs
179
Outline the inheritance of achondroplasia
Autosomal dominant, normally sporadic mutation
180
What is achondroplasia caused by ?
Mutations in the FGF3 receptor, meaning it is permanently expressed resulting in reduced chondrocyte activity
181
What drug can be used in achondroplasia to promote growth ?
Vosoritide
182
What are the 4 medial ankle ligaments ?
Tibiocalcaneal, tibionavicular, tibiotalar (anterior and posterior), plantar calcaneonavicular
183
What are the 3 lateral ankle ligaments ?
Talofibukar (post and ant), calcaneofibular
184
What is an ankle sprain ?
Damage to ligaments
185
What is an ankle strain ?
Damage to muscle or tendon
186
What are the 3 retinacula groups of the ankle?
Flexor
Extensor (sup and inf)
Fibular (sup and inf)
187
What maintains the foot arch ?
Plantar aponeurosis
188
What else in involved in foot arch maintenance?
Calcaneonavicular ligament aka SPRING ligament
189
How many veins is each artery surrounded by ?
2
190
What are the top 5 most common autoimmune diseases ?
Graves’ disease , RA, Thyroiditis, vitiligo , type 1 diabetes
191
What are the multi factorial causes of autoimmunity ?
Genetic, infection and environment exposure, immune regulation
192
Name 3 possible autoimmunity genotypes ?
HLA-DR4 alleles, PTPN22, CTLA4 ( and cytokines)
193
What is positive thymic selection ?
When T-cells survive despite reaction to self-antigens
194
What is negative thymic selection ?
When T-cells undergo cell death for responding to self-antigens
195
What is the treatment for FOXP3 gene mutation ?
Bone marrow transplant, immunosuppressant therapies
196
What MHC gene is RA associated with ?
DR4
197
What MHC gene is Crohn’s disease associated with ?
CARD15
198
What is the specific target of Graves’ disease ?
TSH receptor
199
What does Graves’ disease lead to ?
Overproduction of thyroid hormones
200
What happens is Myastenia gravis ?
Antibody blocks acetylcholine receptors, no Na+ influx occurs and therefore no muscle contraction
201
What are 3 examples of organ specific autoimmunity ?
Addison’s disease, MS, Guillain-Barre Syndrome
202
What are 3 examples of non-organ specific autoimmunity?
RA, Scleroderma, systemic lupus
203
What does Gillian-Barre syndrome cause ?
Acute paralysis
204
What is the formula for hydroxyapatite ?
Ca10(PO4)6(OH)2
205
What are the 3 possible pathologies of metabolic bone disorders ?
Loss of mineralisation
Bone mass (low or high)
Turnover (low or high)
206
What are biochemical tests for metabolic bone disorders ?
Serum Ca/PO4(3-)
PTH
Vit.D activity
Alkaline phosphates
207
What is the difference between menopausal osteoporosis and normal osteoporosis ?
Menopausal involves reduces mineral mass whereas normal involves reduced total bone mass
208
What do corticosteroids effect in bone remodelling?
They increase bone resorption rate and depth , and inhibit osteoblasts activity
209
What causes high calcium and high PTH ?
Primary hyperparathyroidism
210
What causes low calcium and high PTH ?
Secondary hyperparathyroidism due to renal impairment or Vit D deficiency
211
What cause low calcium and low PTH ?
Hypoparathyroidism due to autoimmunity, surgical thyroid removal and radiotherapy
212
What causes high calcium and low PTH ?
Malignancy, excessive intake, medications, granulomatous disorders
213
What happens if corrected calcium is above 2.8?
Test for PTH levels = undetectable suggests malignancy, detectable or high suggests primary hyperparathyroidism
214
What is Paget’s disease ?
Rapid bone turnover , both resorption and formation are increased. Causes disorganised bone
215
What is an example of a selective NSAID ?
Celecoxib
216
What is the benefit of Celecoxib for the GI tract ?
Decreased risk of GI side effects ( increased risk of CV side effects)
217
What are corticosteroids useful for treating ?
RA, Lupus, Acute Leukaemia, Asthma, Psoriasis, Anaphylaxis, Transplantation, Addison’s disease, UC, Crohn
218
What are the key symptoms of RA?
Joint pain, stiffness in the morning, swelling, fatigue (in systemic weight loss and fevers)
219
What immune system is responsible for RA (primarily) ?
ADAPTIVE
220
What type of gut bacteria is enriched in early RA ?
Prevotella Copri
221
What type of T cells are defected in RA?
CD4
222
What treatments are used for RA?
NSAIDs, corticosteroids, DMARDs (methotrexate)
223
What is seen as the conductor in RA ?
TNF-alpha (produces cytokine signalling)
224
Give an example of an anti-TNF drug ?
Infliximab
225
Describe costovertebral joints ?
Rib articulating with superior Demi-facet of corresponding vertebrae + inferior Demi-facet of vertebrae superior
226
Describe costotransverse joints ?
Tubercle of rib articulates with corresponding transverse process of vertebrae
227
What are the openings at the top and bottom of the ribcage called ?
Superior + inferior thoracic aperture
228
What can occur in cervical rib ?
Compression of underlying nerves and vessels, can present similar to Klumpke’s syndrome
229
How much does the diaphragm move in quiet breathing ?
1-2 cm
230
How much does the diaphragm move in forced breathing ?
6-10 cm
231
From anterior to posterior, what structures pass through the diaphragm?
IVC
Oesophagus
Aorta
232
What nerve supplies the diaphragm ?
Phrenic nerve
233
What vertebrae does the phrenic nerve arise from ?
C3, 4 + 5 (keeps the diaphragm alive)
234
From internal to external, outline the layers if a blood vessel
Tunica intima
Internal lamina
Tunica media
External lamina (with adventitious fibroblasts)
Nerves
Perivascular adipose tissue (PVAT)
235
What does eutrophic mean ?
Normal blood vessel structure
236
What does hypotrophic mean ?
Widening of blood vessels, either due to less wall tissue or adventitious widening
237
What does hypertrophic mean ?
Narrowing of a vessel, due to increased wall tissue or widening adventitia
238
What makes up blood vessel walls ?
Endothelium, collagen (type 1) elastic fibres and other cells
239
What is key in vascular remodelling ?
Angiotensin
240
Outline the beginning steps of atherosclerosis
Insult to vascular endothelium
Increased adhesion and transmigration of leukocytes
Increased lipid permeability
Generation of cytokines
Inflammation focus established
241
What happens during fatty streak formation ?
Lipid-laden foam cells form under endothelium
242
What causes an advanced lesion in blood vessels to form ?
Macrophage accumulation
Formation of necrotic core
Fibrous cap formation
243
What causes thrombosis ?
Fibrous cap thins, intraplaque haemorrhage occurs and the vessel becomes blocked
244
What is cholesterol essential for ?
Cell membranes, maintaining membrane permeability + steroid and fat-soluble vitamin formation
245
What is the livers role in cholesterol?
Monitors levels, regulates (through synthesis, absorption and bile secretion)
246
What is VLDL ?
LDL precursor, carries synthesised TGs from liver to adipose tissue
247
What is LDL ?
Major cholesterol reservoir, taken up via endocytosis by LDL receptors
BAD
248
What is HDL ?
GOOD cholesterol, absorbs cholesterol released by dying cells
Acts as reverse transport to take cholesterol back to liver
249
Exogenous cholesterol pathway
Intestine - chylomicron - capillary (can become adipose) - chylomicron remnant - bind to receptors on liver - cholesterol produced
250
What blood vessels does PVAT not surround ?
Cerebral
251
Outline PVAT composition and nerve supply
Adipocytes (+ fibroblasts and immune)
Nerve supply = adrenergic nerve fibres
They release adipokines
252
Endogenous pathways of cholesterol transport
Liver VLDL - capillary (can become adipose) - IDL - IDL to LDL - LDL binds to receptors and deposits cholesterol
253
What is familial hypercholesterolaemia ?
Reduced LDL receptors on liver
VDL is converted to IDL in the capillaries
254
What are the signs of FH ?
Xanthomas = fatty deposits in skin (elbows,knees,buttocks and tendons)
Xanthelasmas = fatty deposits in the eyelids
Arcus senilis = a white ring around the cornea
255
What do statins do ?
They are competitive inhibitors of the rate-limiting stem in cholesterol biosynthesis
Less cholesterol may stimulate LDL receptor up-regulation
256
What are the 5 main causes of hypertension ?
Smoking!
Obesity !
Diet!
Exercise (lack of) !
Genetics
257
What are the risks of hypertension ?
Atherosclerosis, stroke, myocardial infarction, heart failure, renal failure , retinopathy
258
What is the BP calculation ?
BP = TPR x CO
CO= HR x SV
259
Outline beta-adrenoceptor blockers
Propranolol (B1+B2) and Atenolol (B1)
Completive reversible antagonists
Lower BP by blocking sympathetic tone on heart
lowering HR,SV and CO
260
Outline alpha-adrenoceptor blockers ?
Phentolamine (a1+a2) and Doxazosin,Prazosin (a1 selective)
Competitive reversible antagonists
Lower BP by lowering sympathetic tone in arterioles
Lowers TPR
261
Outline ACE inhibitors
Captopril and Enalapril
Reduce angiotensin II formation - lowers TPR
Reduces aldosterone formation (stimulated by angiotensin II) - lowers blood volume
262
Outline diuretics
Bendroflumethiazide
Lowers BP by reducing blood volume
Reduces renal reabsorption of Na+ and water
263
Outline Calcium channel blockers
Verapamil, Diltiazem, Nifedipine
Block Ca entry into vascular smooth muscle causing vasodilation - lowers TPR
Block Ca entry into cardia muscle - lowers HR,SV and CO
