Term
| What movements does the knee joint articulate |
|
Definition
-flexion and extension
-internal and external rotation
-6 total degrees of freedom |
|
|
Term
| what are the two articulating joints within the knee |
|
Definition
patella-femoral
tibiofemoral |
|
|
Term
| What are the ligaments in the knee joint |
|
Definition
-medial and lateral collateral ligaments
-anterior and posterior cruciate ligaments
-patella ligament |
|
|
Term
|
Definition
-protein polysaccharides synthesised by chondrocytes
-negatively charged
-protein core with GAGs attached
MAIN ONE IN CARTILAGE IS AGGRECAN |
|
|
Term
| what is the main role of chondrocytes |
|
Definition
| breakdown/remake/maintain matrix |
|
|
Term
|
Definition
|
|
Term
| what happens in early osteoarthritis? |
|
Definition
1.cartilage fibrilation and decreased proteoglycans = ;pad bearing capactiy and lubrication deteriarates
2.cartilage decolours/softens and surface irregulates
3.more susceptable to mechanical damage
4.collagen network deteriorates and allows increased water retention = stiffness of tissue
5.chondrocytes attempt repair
6.collagen breaks down = production of collagenases |
|
|
Term
| what happens in advanced osteoarthritis? |
|
Definition
1.full thickness defects develop done to the bone
2.osteochondral fractures
3.deformation of bone and loss of PGs
4.wound healing response (cells from bone marrow)
5.fibrocartilage is formed (worse than hyaline) |
|
|
Term
| What role do chondrocytes have in OA? |
|
Definition
source of destructive enzymes
matrix remodelling
synthesise cytokines:
-inflammatory
-catabolic
-inhibitory
-anabolic |
|
|
Term
| what are matrix metalloproteases (MMP) |
|
Definition
produced by chondrocytes and are involved in matrix turnover, tissue remodelling and resorption.
tightly regulated by cytokines
they act on collagens, proteoglycans and other non-collagenous proteins of cartilage |
|
|
Term
|
Definition
collagenous
gelatinous
GAGs
others |
|
|
Term
| What is the initiator of OA? |
|
Definition
disease of whole joint not just cartilage
abnormal mechanical loading
biochemical factors |
|
|
Term
| How is OA and the immune system related? |
|
Definition
| -increased amount of complement proteins in the synovial fluid of patients with OA than healthy ones |
|
|
Term
| what is the drug target for drugs that may prevent OA |
|
Definition
|
|
Term
| What is current treatment for OA |
|
Definition
drugs target symptoms rather than causes
moderate pain relief
concerning side effects |
|
|
Term
| What is Rheumatoid arthritis |
|
Definition
systematic inflammatory autoimmune disease
synovial joint
inflammatory response of synovium
proliferation of synovial cells = excessive synovial fluid
=destruction of cartilage and stiffness of joints |
|
|
Term
| What are the causes of RA |
|
Definition
genes
environmental factors
chance
SMOKING IS MOST SIGNIFICANT |
|
|
Term
| Describe the pathogenesis of RA |
|
Definition
1.lungs encounter smoke
2.macrophages are activated
3.cells undergo apoptosis/necrosis/both
4.increased synthesis of peptidylarginine deiminases
5.causes citrullination of proteins in lungs
6.these bind to HLA-DR molecules on APC
7.smoking further contributes to t-cell and b-cell activation by triggering APCs in lung leading to increased antibody production
8.this occurs years before onset of RA and leads to immune complex formation |
|
|
Term
| What are the treatments for RA |
|
Definition
1.pharmaceuticals
2.antiinflammatories
3.analgesics. |
|
|
Term
| What is the difference between autosomal and sex-linked inheritance? |
|
Definition
A=trait/disorder on autosomal gene
S=on sex gene |
|
|
Term
|
Definition
| all dna coding for an organism |
|
|
Term
| define somatic cell mutation |
|
Definition
| cannot be transmitted to offspring |
|
|
Term
|
Definition
| can be passed on to offspring |
|
|
Term
| what are chromosomal mutations |
|
Definition
extra/lost chromosomes
damage to chromosomes |
|
|
Term
| what are submicroscopic muations |
|
Definition
| changes to more nucleotides |
|
|
Term
|
Definition
| involves the replacement of a single nucleotide by another |
|
|
Term
|
Definition
transition
transversion
deletions
insertions |
|
|
Term
| define a synonymous mutation |
|
Definition
| no change (produces the same amino acid) |
|
|
Term
| define a non-synonymous mutation |
|
Definition
| alteration in the encoded polypeptide which results in disease. There are 3 things: missense, nonsense, frameshift |
|
|
Term
| what happens in a missense mutation? |
|
Definition
SNPs lead to coding for a different aa and hence altered protein.
reduces activity or altered characteristics |
|
|
Term
| what happens in a nonsense mutation? |
|
Definition
substitution that leads to generation of a stop codon therefore premature termination of translation.
unlikely to retain biological function. |
|
|
Term
| what happens in a frameshift mutation? |
|
Definition
when a non multiple of 3 is inserted the reading frame is disrupted.
abnormal protein function.
may also result in a subsequent stop codon |
|
|
Term
| how can a mutation cause loss of function to a protein |
|
Definition
reduced activity (hypomorph)
decreased stability (null allele)
loss of gene product
inherited enzyme function reduction |
|
|
Term
| how can a mutation cause gain of function to a protein |
|
Definition
increased level of gene receptors
development of new functions of gene product |
|
|
Term
| What is huntingtons disease caused by |
|
Definition
expanded triplet repeat mutations of the huntington gene cause aggregations in the CNS
single gene, autosomal dominant inheritance
slow selected cell death in CNS
movement disorder and intellectual impairments |
|
|
Term
|
Definition
cell surface receptors allowing for endocytosis of LDLs
present on all nucleated cells, important in liver |
|
|
Term
|
Definition
transport mechanism for fats in an aqueous environment
transport cholesterol and triglycerides |
|
|
Term
|
Definition
1. ldl binds to receptor in clathrin coated pit
2.forms vesicle which fuses with endosome containing H+
3. protons cause receptor and ldl to go to opposite ends
4.vesicle splits, receptor goes back to surface
5.acid hydrolase degrades ldl's into amino acids and cholesterol |
|
|
Term
| What are the effects of LDL receptor mutations? |
|
Definition
1. ER ->receptor synthesis
2.Goldi -> receptor modification
3.Cholesterol cannot bind to receptors
4.cannot endocytose into clathrin pits
5.receptors cannot traffic back |
|
|
Term
| what do all ldl receptor mutations cause |
|
Definition
| high levels of cholesterol in the blood |
|
|
Term
| What is familial hypercholesterolemia FH? |
|
Definition
| inability to internalise LDLs at the normal rate and high blood LDL levels. LDL's circulate for twice as long. |
|
|
Term
| What accelerated atherosclerosis lead to |
|
Definition
|
|
Term
| which is more common hetero or homo? |
|
Definition
|
|
Term
|
Definition
| disease of the arterial characterised by the deposition of fatty material on inner walls. no symptoms at first |
|
|
Term
| What are the 3 fatty deposit types and where do they appear? |
|
Definition
Xarithoma -> tendons (hands, elbow, knees and feet)
Xarithelamas -> eyelids
Corneal arcus -> iris and cornea |
|
|
Term
| What cholesterol levels fo FH patients have? |
|
Definition
|
|
Term
| What are the effects of atherosclerosis |
|
Definition
-cholesterol deposited in artery wall
-chronic inflammatory response
-weakening/hardening/narrowing of arteries |
|
|
Term
| What does atherosclerosis increase your risk of |
|
Definition
angina pectoris
coronary thrombosis
myocardial infarction |
|
|
Term
| How is hetereozygous FH treated? |
|
Definition
-prevention of CVD:lifestyle, diet, exercise
-pharmaceuticals: statins, bile acid sequestrants, fenofibrate |
|
|
Term
| How is homozygous FH treated? |
|
Definition
-drug therapy
-xanthoma removal
-invasive treatments |
|
|
Term
|
Definition
all diseases of the heart and circulation:
-coronary heart disease
-angina
-heart attack
-congenital heart disease
-stroke |
|
|
Term
| Describe the mechanism of atherosclerosis |
|
Definition
1.increased blood plasma lipids
2.circulatin monocytes begin removing excess cholesterol rich lipoproteins
3.monocytes filled with lipid droplets become foam cells and attach to endothelial lining of blood vessel walls
4.they release cytokines causing SMC to divide
5.other monocytes invade area
6.endothelial cells start phagocytising lipids
7.plaque formation |
|
|
Term
| How can atherosclerosis lead to clot formation |
|
Definition
1.when conditions persits, endothelial cells become swollen with lipids and gaps appear in the lining
2. rbc attach to exposed collagen and clot forms |
|
|
Term
| What causes atherosclerosis |
|
Definition
smoking
diabetes
high fat diet
sedentary lifestyle
overweight
high blood pressure/cholesterol |
|
|
Term
| What 3 parallel circuits is the cardiovascular system divided into |
|
Definition
pulmonary
coronary
systematic |
|
|
Term
|
Definition
medical imagining technique used to visualise blood vessels and organs.
injection of radio-opaque dye into the coronary circulation and detects blockages using xrays. |
|
|
Term
| What events lead to angina pectoris/heart attack? |
|
Definition
accumulation of atherosclerotic plaques in coronary arteries
blood flow to the myocardium is restricted |
|
|
Term
|
Definition
1.patient will come to the doctor with chest pain
2.they will be injected with streptokinase to break up blood clots
3.once stable, angiography will be used to detect CA blockages |
|
|
Term
| Describe angioplasty (PTCA) |
|
Definition
1.balloon catheter is threaded to destructed area
2.balloon is inflated and stretches arterial wall and squashes plaque
3.lumen is widened, balloon is deflated and catheter is withdrawn |
|
|
Term
| What are the problems associated with angioplasty |
|
Definition
-balloon inflation induces ischaemia (inadequate blood supply in heart)
-damage to vessel could lead to closure of the artery again |
|
|
Term
|
Definition
-surgical procedure that diverts blood around narrowed/clogged parts of the major arteries
-conduit normally harvested from the saphenous vein from the leg
-routine to have 2-4 grafts to bypass blocked arteries |
|
|
Term
| What are the problems associated with pypass |
|
Definition
open chest surgery
involves stopping the heart
grafts can resterose (narrow) |
|
|
Term
| What is hypertension and give the figures |
|
Definition
abnormally high blood pressure
systolic >140mmHg
diastolic >99mmHg |
|
|
Term
| what is hypertrophic cardiomyopathy |
|
Definition
| muscle wall becomes thickened which makes the muscle stiff and therefore blood is harder to pump around body |
|
|
Term
| what is dilated cardiomyopathy |
|
Definition
| thinning of the ventricular walls enlarges the interior of the ventricular chamber. there is impaired ventricular relaxation and the heart muscle becomes weak. |
|
|
Term
| what is left ventricular noncompaction |
|
Definition
| trabeculated ventricular walls create a spongy appearance, prominent in the left ventricular wall. |
|
|
Term
| what is cardiac hypertrophy |
|
Definition
| abnormal enlargement of the heart muscle, resulting from increased cardiomyocyte size |
|
|
Term
| How can increased SV result from heart failure |
|
Definition
-increased ESV by reduced contractility
-decreased diastolic volume by impaired ventricular filling |
|
|
Term
| How is heart failure diagnosed |
|
Definition
blood tests
breathing test
ECG
echocardiogram |
|
|
Term
| What is Wolk Parkinson White sydrome |
|
Definition
pre-excitation of ventricular tissue
caused by abnormally fast conduction |
|
|
Term
| What are the characteristics |
|
Definition
short p-r interval
slurred upstroke of the QRS
QRS widened |
|
|
Term
|
Definition
electrophysiology study followed by cathater ablation of accesory pathway
surgery/drug therapies |
|
|
Term
| What is diabetes insipidus |
|
Definition
| produces a copious volume of dilute urine due to the failure to reabsorb water in the renal collecting duct |
|
|
Term
| why is the collecting duct unable to reabsorb water |
|
Definition
there is no vasopressin (central diabetes insipidus)
kidney cannot respond to it (nephrogenic diabetes insipidus) |
|
|
Term
| How is the collecting ducts permeability controlled? |
|
Definition
1.vasopressin/adh binds to receptors on basolateral membrane
2.GPCR events follow...PKA phosphorylates AQP2
3.APQ2 moved to the apical membrane is inserted
4.water can now enter the tubular fluid and leave through APQ3/4 |
|
|
Term
|
Definition
| failure to produce functional vasopressin |
|
|
Term
| how is central diabetes aquired |
|
Definition
damage to the hypothalamus and or pituitory:
-trauma
-tumour |
|
|
Term
| what is nephrogenic diabetes |
|
Definition
| collecting ducts are unable to respond to vasopressin |
|
|
Term
| how is nephrogenic diabetes aquired |
|
Definition
drugs (lithium)
electrolyte distrubances
kidney diseases |
|
|
Term
| what is dipsogenic diabetes insipidus |
|
Definition
| excessive drinking leads to water overload and hyponatraemia |
|
|
Term
|
Definition
| water is restricted whilst weight, plasma and urine osmolarity and urine output are monitored |
|
|
Term
| what is the treatment for central DI |
|
Definition
| dDAVP a synthetic vasopressin |
|
|
Term
| what is the treatment for nephrogenic DI |
|
Definition
water replacement
salt restriction
thiazide diuretics |
|
|
Term
|
Definition
all diseases of the heart and circulation:
-coronary heart disease
-angina
-heart attack
-congenital heart disease
-stroke |
|
|
Term
| Describe the mechanism of atherosclerosis |
|
Definition
1.increased blood plasma lipids
2.circulatin monocytes begin removing excess cholesterol rich lipoproteins
3.monocytes filled with lipid droplets become foam cells and attach to endothelial lining of blood vessel walls
4.they release cytokines causing SMC to divide
5.other monocytes invade area
6.endothelial cells start phagocytising lipids
7.plaque formation |
|
|
Term
| How can atherosclerosis lead to clot formation |
|
Definition
1.when conditions persits, endothelial cells become swollen with lipids and gaps appear in the lining
2. rbc attach to exposed collagen and clot forms |
|
|
Term
| What causes atherosclerosis |
|
Definition
smoking
diabetes
high fat diet
sedentary lifestyle
overweight
high blood pressure/cholesterol |
|
|
Term
| What 3 parallel circuits is the cardiovascular system divided into |
|
Definition
pulmonary
coronary
systematic |
|
|
Term
|
Definition
medical imagining technique used to visualise blood vessels and organs.
injection of radio-opaque dye into the coronary circulation and detects blockages using xrays. |
|
|
Term
| What events lead to angina pectoris/heart attack? |
|
Definition
accumulation of atherosclerotic plaques in coronary arteries
blood flow to the myocardium is restricted |
|
|
Term
|
Definition
1.patient will come to the doctor with chest pain
2.they will be injected with streptokinase to break up blood clots
3.once stable, angiography will be used to detect CA blockages |
|
|
Term
| Describe angioplasty (PTCA) |
|
Definition
1.balloon catheter is threaded to destructed area
2.balloon is inflated and stretches arterial wall and squashes plaque
3.lumen is widened, balloon is deflated and catheter is withdrawn |
|
|
Term
| What are the problems associated with angioplasty |
|
Definition
-balloon inflation induces ischaemia (inadequate blood supply in heart)
-damage to vessel could lead to closure of the artery again |
|
|
Term
|
Definition
-surgical procedure that diverts blood around narrowed/clogged parts of the major arteries
-conduit normally harvested from the saphenous vein from the leg
-routine to have 2-4 grafts to bypass blocked arteries |
|
|
Term
| What are the problems associated with pypass |
|
Definition
open chest surgery
involves stopping the heart
grafts can resterose (narrow) |
|
|
Term
| What is hypertension and give the figures |
|
Definition
abnormally high blood pressure
systolic >140mmHg
diastolic >99mmHg |
|
|
Term
| what is hypertrophic cardiomyopathy |
|
Definition
| muscle wall becomes thickened which makes the muscle stiff and therefore blood is harder to pump around body |
|
|
Term
| what is dilated cardiomyopathy |
|
Definition
| thinning of the ventricular walls enlarges the interior of the ventricular chamber. there is impaired ventricular relaxation and the heart muscle becomes weak. |
|
|
Term
| what is left ventricular noncompaction |
|
Definition
| trabeculated ventricular walls create a spongy appearance, prominent in the left ventricular wall. |
|
|
Term
| what is cardiac hypertrophy |
|
Definition
| abnormal enlargement of the heart muscle, resulting from increased cardiomyocyte size |
|
|
Term
| How can increased SV result from heart failure |
|
Definition
-increased ESV by reduced contractility
-decreased diastolic volume by impaired ventricular filling |
|
|
Term
| How is heart failure diagnosed |
|
Definition
blood tests
breathing test
ECG
echocardiogram |
|
|
Term
| What is Wolk Parkinson White sydrome |
|
Definition
pre-excitation of ventricular tissue
caused by abnormally fast conduction |
|
|
Term
| What are the characteristics |
|
Definition
short p-r interval
slurred upstroke of the QRS
QRS widened |
|
|
Term
|
Definition
electrophysiology study followed by cathater ablation of accesory pathway
surgery/drug therapies |
|
|
Term
| What is diabetes insipidus |
|
Definition
| produces a copious volume of dilute urine due to the failure to reabsorb water in the renal collecting duct |
|
|
Term
| why is the collecting duct unable to reabsorb water |
|
Definition
there is no vasopressin (central diabetes insipidus)
kidney cannot respond to it (nephrogenic diabetes insipidus) |
|
|
Term
| How is the collecting ducts permeability controlled? |
|
Definition
1.vasopressin/adh binds to receptors on basolateral membrane
2.GPCR events follow...PKA phosphorylates AQP2
3.APQ2 moved to the apical membrane is inserted
4.water can now enter the tubular fluid and leave through APQ3/4 |
|
|
Term
|
Definition
| failure to produce functional vasopressin |
|
|
Term
| how is central diabetes aquired |
|
Definition
damage to the hypothalamus and or pituitory:
-trauma
-tumour |
|
|
Term
| what is nephrogenic diabetes |
|
Definition
| collecting ducts are unable to respond to vasopressin |
|
|
Term
| how is nephrogenic diabetes aquired |
|
Definition
drugs (lithium)
electrolyte distrubances
kidney diseases |
|
|
Term
| what is dipsogenic diabetes insipidus |
|
Definition
| excessive drinking leads to water overload and hyponatraemia |
|
|
Term
|
Definition
| water is restricted whilst weight, plasma and urine osmolarity and urine output are monitored |
|
|
Term
| what is the treatment for central DI |
|
Definition
| dDAVP a synthetic vasopressin |
|
|
Term
| what is the treatment for nephrogenic DI |
|
Definition
water replacement
salt restriction
thiazide diuretics |
|
|
